Life | Editor’s choice

15 pages, 1675 KiB

Open AccessEditor’s ChoiceArticle

CEACAM6’s Role as a Chemoresistance and Prognostic Biomarker for Pancreatic Cancer: A Comparison of CEACAM6’s Diagnostic and Prognostic Capabilities with Those of CA19-9 and CEA

by Benediktas Kurlinkus, Marija Ger, Algirdas Kaupinis, Eugenijus Jasiunas, Mindaugas Valius and Audrius Sileikis

Life 2021, 11(6), 542; https://doi.org/10.3390/life11060542 - 09 Jun 2021

Cited by 7 | Viewed by 2392

Abstract

Survival rates from pancreatic cancer have remained stagnant for decades due to the heterogenic nature of the disease. This study aimed to find a new advanced biomarker and evaluate its clinical capabilities, thus enabling more individualised pancreatic cancer management. Between 2013 and 2020, [...] Read more.

Survival rates from pancreatic cancer have remained stagnant for decades due to the heterogenic nature of the disease. This study aimed to find a new advanced biomarker and evaluate its clinical capabilities, thus enabling more individualised pancreatic cancer management. Between 2013 and 2020, 267 patients were included in the study. Surgically collected pancreatic tissue samples were analysed via high-definition mass spectrometry. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) was discovered as a possible promising pancreatic cancer biomarker. The predominance of CEACAM6 to pancreatic cancer was validated using antibodies in tissue samples. CEACAM6, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) blood serum concentrations were evaluated for clinical evaluation and comparison. Kaplan–Meier survival analyses were used to evaluate disease-free survival (DFS) and overall survival (OS). Poorer overall survival was significantly dependent on increased CEACAM6 blood serum concentrations (17.0 vs. 12.6 months, p = 0.017) in pancreatic cancer patients after radical treatment and adjuvant chemotherapy. Increased CEA and CA19-9 concentrations showed no significant dependencies with survival. Thus, CEACAM6 is a promising new biomarker with significant prognostic value and prediction of chemoresistance properties, enabling the improvement of individualised approaches to patients with pancreatic cancer. Full article

(This article belongs to the Special Issue Emerging Biomarkers: Recent Findings and Its Application in Pathological Conditions Detection)

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14 pages, 2526 KiB

Open AccessEditor’s ChoiceArticle

Effect of the Chinese Herbal Medicine SS-1 on a Sjögren’s Syndrome-Like Disease in Mice

by Po-Chang Wu, Shih-Chao Lin, Lauren Panny, Yu-Kang Chang, Chi-Chien Lin, Yu-Tang Tung and Hen-Hong Chang

Life 2021, 11(6), 530; https://doi.org/10.3390/life11060530 - 07 Jun 2021

Cited by 1 | Viewed by 4126

Abstract

Sjögren’s syndrome (SS) is an inflammatory autoimmune disease primarily affecting the exocrine glands; it has a major impact on patients’ lives. The Chinese herbal formula SS-1 is composed of Gan Lu Yin, Sang Ju Yin, and Xuefu Zhuyu decoction, which exerts anti-inflammatory, immunomodulatory, [...] Read more.

Sjögren’s syndrome (SS) is an inflammatory autoimmune disease primarily affecting the exocrine glands; it has a major impact on patients’ lives. The Chinese herbal formula SS-1 is composed of Gan Lu Yin, Sang Ju Yin, and Xuefu Zhuyu decoction, which exerts anti-inflammatory, immunomodulatory, and antifibrotic effects. Our previous study demonstrated that SS-1 alleviates clinical SS. This study aimed to evaluate the efficacy and mechanism of the Chinese herbal formula SS-1 for salivary gland protein-induced experimental Sjögren’s syndrome (ESS). These results showed that ESS treatment with the Chinese herbal formula SS-1 (1500 mg/kg) significantly alleviated the severity of ESS. We found that SS-1 substantially improved saliva flow rates in SS mice and ameliorated lymphocytic infiltrations in submandibular glands. In addition, salivary gland protein-induced SS in mice treated with SS-1 significantly lowered proinflammatory cytokines (including IFN-γ, IL-6, and IL-17A) in mouse salivary glands and decreased serum anti-M3R autoantibody levels. In addition, we found that CD4+ T cells isolated from SS-1-treated SS mice significantly reduced the percentages of IFN-γ-producing CD4+ T cells (Th1) and IL-17A-producing CD4+ T cells (Th17). Our data show that SS-1 alleviates ESS through anti-inflammatory and immunomodulatory effects, which provides new insight into the clinical treatment of SS. Full article

(This article belongs to the Special Issue Regulation of Natural Products to Immunity)

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21 pages, 746 KiB

Open AccessEditor’s ChoiceReview

Altered Bone Status in Rett Syndrome

by Alessandra Pecorelli, Valeria Cordone, Maria Lucia Schiavone, Carla Caffarelli, Carlo Cervellati, Gaetana Cerbone, Stefano Gonnelli, Joussef Hayek and Giuseppe Valacchi

Life 2021, 11(6), 521; https://doi.org/10.3390/life11060521 - 03 Jun 2021

Cited by 6 | Viewed by 3954

Abstract

Rett syndrome (RTT) is a monogenic neurodevelopmental disorder primarily caused by mutations in X-linked MECP2 gene, encoding for methyl-CpG binding protein 2 (MeCP2), a multifaceted modulator of gene expression and chromatin organization. Based on the type of mutation, RTT patients exhibit a broad [...] Read more.

Rett syndrome (RTT) is a monogenic neurodevelopmental disorder primarily caused by mutations in X-linked MECP2 gene, encoding for methyl-CpG binding protein 2 (MeCP2), a multifaceted modulator of gene expression and chromatin organization. Based on the type of mutation, RTT patients exhibit a broad spectrum of clinical phenotypes with various degrees of severity. In addition, as a complex multisystem disease, RTT shows several clinical manifestations ranging from neurological to non-neurological symptoms. The most common non-neurological comorbidities include, among others, orthopedic complications, mainly scoliosis but also early osteopenia/osteoporosis and a high frequency of fractures. A characteristic low bone mineral density dependent on a slow rate of bone formation due to dysfunctional osteoblast activity rather than an increase in bone resorption is at the root of these complications. Evidence from human and animal studies supports the idea that MECP2 mutation could be associated with altered epigenetic regulation of bone-related factors and signaling pathways, including SFRP4/WNT/β-catenin axis and RANKL/RANK/OPG system. More research is needed to better understand the role of MeCP2 in bone homeostasis. Indeed, uncovering the molecular mechanisms underlying RTT bone problems could reveal new potential pharmacological targets for the treatment of these complications that adversely affect the quality of life of RTT patients for whom the only therapeutic approaches currently available include bisphosphonates, dietary supplements, and physical activity. Full article

(This article belongs to the Special Issue Biochemical Modulators in Chronic Diseases: The Antioxidant /Anti-inflammatory Interdependence)

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19 pages, 1812 KiB

Open AccessEditor’s ChoiceArticle

Functional Analysis of Brain Imaging Suggests Changes in the Availability of mGluR5 and Altered Connectivity in the Cerebral Cortex of Long-Term Abstaining Males with Alcohol Dependence: A Preliminary Study

by Yo-Han Joo, Jeong-Hee Kim, Hang-Keun Kim, Young-Don Son, Paul Cumming and Jong-Hoon Kim

Life 2021, 11(6), 506; https://doi.org/10.3390/life11060506 - 30 May 2021

Cited by 3 | Viewed by 2711

Abstract

Direct in vivo evidence of altered metabotropic glutamate receptor-5 (mGluR5) availability in alcohol-related disorders is lacking. We performed [¹¹C]ABP688 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in prolonged abstinent subjects with alcohol dependence to examine alterations of [...] Read more.

Direct in vivo evidence of altered metabotropic glutamate receptor-5 (mGluR5) availability in alcohol-related disorders is lacking. We performed [¹¹C]ABP688 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in prolonged abstinent subjects with alcohol dependence to examine alterations of mGluR5 availability, and to investigate their functional significance relating to neural systems-level changes. Twelve prolonged abstinent male subjects with alcohol dependence (median abstinence duration: six months) and ten healthy male controls underwent [¹¹C]ABP688 PET imaging and 3-Tesla MRI. For mGluR5 availability, binding potential (BP_ND) was calculated using the simplified reference tissue model with cerebellar gray matter as the reference region. The initial region-of-interest (ROI)-based analysis yielded no significant group differences in mGluR5 availability. The voxel-based analysis revealed significantly lower [¹¹C]ABP688 BP_ND in the middle temporal and inferior parietal cortices, and higher BP_ND in the superior temporal cortex in the alcohol dependence group compared with controls. Functional connectivity analysis of the rs-fMRI data employed seed regions identified from the quantitative [¹¹C]ABP688 PET analysis, which revealed significantly altered functional connectivity from the inferior parietal cortex seed to the occipital pole and dorsal visual cortex in the alcohol dependence group compared with the control group. To our knowledge, this is the first report on the combined analysis of mGluR5 PET imaging and rs-fMRI in subjects with alcohol dependence. These preliminary results suggest the possibility of region-specific alterations of mGluR5 availability in vivo and related functional connectivity perturbations in prolonged abstinent subjects. Full article

(This article belongs to the Special Issue Glutamate Receptors)

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34 pages, 5672 KiB

Open AccessEditor’s ChoiceReview

Advances in Cereal Crop Genomics for Resilience under Climate Change

by Tinashe Zenda, Songtao Liu, Anyi Dong and Huijun Duan

Life 2021, 11(6), 502; https://doi.org/10.3390/life11060502 - 29 May 2021

Cited by 24 | Viewed by 6670

Abstract

Adapting to climate change, providing sufficient human food and nutritional needs, and securing sufficient energy supplies will call for a radical transformation from the current conventional adaptation approaches to more broad-based and transformative alternatives. This entails diversifying the agricultural system and boosting productivity [...] Read more.

Adapting to climate change, providing sufficient human food and nutritional needs, and securing sufficient energy supplies will call for a radical transformation from the current conventional adaptation approaches to more broad-based and transformative alternatives. This entails diversifying the agricultural system and boosting productivity of major cereal crops through development of climate-resilient cultivars that can sustainably maintain higher yields under climate change conditions, expanding our focus to crop wild relatives, and better exploitation of underutilized crop species. This is facilitated by the recent developments in plant genomics, such as advances in genome sequencing, assembly, and annotation, as well as gene editing technologies, which have increased the availability of high-quality reference genomes for various model and non-model plant species. This has necessitated genomics-assisted breeding of crops, including underutilized species, consequently broadening genetic variation of the available germplasm; improving the discovery of novel alleles controlling important agronomic traits; and enhancing creation of new crop cultivars with improved tolerance to biotic and abiotic stresses and superior nutritive quality. Here, therefore, we summarize these recent developments in plant genomics and their application, with particular reference to cereal crops (including underutilized species). Particularly, we discuss genome sequencing approaches, quantitative trait loci (QTL) mapping and genome-wide association (GWAS) studies, directed mutagenesis, plant non-coding RNAs, precise gene editing technologies such as CRISPR-Cas9, and complementation of crop genotyping by crop phenotyping. We then conclude by providing an outlook that, as we step into the future, high-throughput phenotyping, pan-genomics, transposable elements analysis, and machine learning hold much promise for crop improvements related to climate resilience and nutritional superiority. Full article

(This article belongs to the Special Issue Research Advances in Plant Genomics)

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14 pages, 2995 KiB

Open AccessEditor’s ChoiceArticle

Impact of TSPO Receptor Polymorphism on [¹⁸F]GE-180 Binding in Healthy Brain and Pseudo-Reference Regions of Neurooncological and Neurodegenerative Disorders

by Franziska J. Vettermann, Stefanie Harris, Julia Schmitt, Marcus Unterrainer, Simon Lindner, Boris-Stephan Rauchmann, Carla Palleis, Endy Weidinger, Leonie Beyer, Florian Eckenweber, Sebastian Schuster, Gloria Biechele, Christian Ferschmann, Vladimir M. Milenkovic, Christian H. Wetzel, Rainer Rupprecht, Daniel Janowitz, Katharina Buerger, Robert Perneczky, Günter U. Höglinger, Johannes Levin, Christian Haass, Joerg C. Tonn, Maximilian Niyazi, Peter Bartenstein, Nathalie L. Albert and Matthias Brendel Show full author list Hide full author list

Life 2021, 11(6), 484; https://doi.org/10.3390/life11060484 - 26 May 2021

Cited by 15 | Viewed by 3991

Abstract

TSPO-PET tracers are sensitive to a single-nucleotide polymorphism (rs6971-SNP), resulting in low-, medium- and high-affinity binders (LABs, MABs and HABS), but the clinical relevance of [¹⁸F]GE-180 is still unclear. We evaluated the impact of rs6971-SNP on in vivo [¹⁸F]GE-180 [...] Read more.

TSPO-PET tracers are sensitive to a single-nucleotide polymorphism (rs6971-SNP), resulting in low-, medium- and high-affinity binders (LABs, MABs and HABS), but the clinical relevance of [¹⁸F]GE-180 is still unclear. We evaluated the impact of rs6971-SNP on in vivo [¹⁸F]GE-180 binding in a healthy brain and in pseudo-reference tissue in neuro-oncological and neurodegenerative diseases. Standardized uptake values (SUVs) of [¹⁸F]GE-180-PET were assessed using a manually drawn region of interest in the frontoparietal and cerebellar hemispheres. The SUVs were compared between the LABs, MABs and HABs in control, glioma, four-repeat tauopathy (4RT) and Alzheimer’s disease (AD) subjects. Second, the SUVs were compared between the patients and controls within their rs6971-subgroups. After excluding patients with prior therapy, 24 LABs (7 control, 5 glioma, 6 4RT and 6 AD) were analyzed. Age- and sex-matched MABs (n = 38) and HABs (n = 50) were selected. The LABs had lower frontoparietal and cerebellar SUVs when compared with the MABs and HABs, but no significant difference was observed between the MABs and HABs. Within each rs6971 group, no SUV difference between the patients and controls was detected in the pseudo-reference tissues. The rs6971-SNP affects [¹⁸F]GE-180 quantification, revealing lower binding in the LABs when compared to the MABs and HABs. The frontoparietal and cerebellar ROIs were successfully validated as pseudo-reference regions. Full article

(This article belongs to the Section Radiobiology and Nuclear Medicine)

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6 pages, 201 KiB

Open AccessEditor’s ChoicePerspective

Deep Brain Stimulation and Hypoxemic Perinatal Encephalopathy: State of Art and Perspectives

by Gaëtan Poulen, Emilie Chan-Seng, Emily Sanrey and Philippe Coubes

Life 2021, 11(6), 481; https://doi.org/10.3390/life11060481 - 25 May 2021

Cited by 1 | Viewed by 1843

Abstract

Cerebral palsy (CP) is a heterogeneous group of non-progressive syndromes with lots of clinical variations due to the extent of brain damages and etiologies. CP is majorly defined by dystonia and spasticity. The treatment of acquired dystonia in CP is very difficult. Many [...] Read more.

Cerebral palsy (CP) is a heterogeneous group of non-progressive syndromes with lots of clinical variations due to the extent of brain damages and etiologies. CP is majorly defined by dystonia and spasticity. The treatment of acquired dystonia in CP is very difficult. Many pharmacological treatments have been tried and surgical treatment consists of deep brain stimulation (continuous electrical neuromodulation) of internal globus pallidus (GPi). A peculiar cause of CP is neonatal encephalopathy due to an anoxic event in the perinatal period. Many studies showed an improvement of dystonia in CP patients with bilateral GPi DBS. However, it remains a variability in the range of 1% to 50%. Published case-series concerned mainly small population with a majority of adult patients. Selection of patients according to the clinical pattern, to the brain lesions observed on classical imaging and to DTI is the key of a high success rate of DBS in children with perinatal hypoxemic encephalopathy. Only a large retrospective study with a high number of patients in a homogeneous pediatric population with a long-term follow-up or a prospective multicenter trial investigation could answer with a high degree of certitude of the real interest of this therapeutic in children with hypoxemic perinatal encephalopathy. Full article

(This article belongs to the Special Issue Dystonia and Related Disorders: From Bench to Bedside)

17 pages, 411 KiB

Open AccessEditor’s ChoiceReview

BiTEs, DARTS, BiKEs and TriKEs—Are Antibody Based Therapies Changing the Future Treatment of AML?

by Cecily Allen, Amer M. Zeidan and Jan Philipp Bewersdorf

Life 2021, 11(6), 465; https://doi.org/10.3390/life11060465 - 23 May 2021

Cited by 25 | Viewed by 6930

Abstract

Nearly four decades after their conceptualization, antibody-based therapies are slowly being added to the treatment landscape of acute myeloid leukemia (AML). While the antibody–drug conjugate gemtuzumab ozogamicin is the only antibody-based therapy that has been approved for AML treatment thus far, several bispecific [...] Read more.

Nearly four decades after their conceptualization, antibody-based therapies are slowly being added to the treatment landscape of acute myeloid leukemia (AML). While the antibody–drug conjugate gemtuzumab ozogamicin is the only antibody-based therapy that has been approved for AML treatment thus far, several bispecific antibodies have been developed and shown early encouraging results. Bispecific antibodies comprise a wide variety of constructs that share the common concept of simultaneous binding of a surface target on malignant cells and most commonly CD3 on T cells leading to an endogenous, HLA-independent, immune response against malignant cells. However, the use of bispecific antibodies in AML has been limited by the absence of highly specific leukemia-associated antigens leading to on-target, off-leukemia side effects as well as reduced efficacy due to antigen escape. Herein, we discuss the history and evolution of bispecific T cell engagers as well as various adaptations such as dual affinity retargeting antibodies, bi- and tri-specific killer engager antibodies. Common side effects including cytokine release syndrome and management thereof are highlighted. Lastly, we expound on the future direction and integration of such antibody-based therapies with other immunotherapies (programmed cell death-1 inhibitors and chimeric antigen receptor T cells). Full article

(This article belongs to the Special Issue Bispecific Antibodies: Design, Isolation, Perspectives of Use)

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15 pages, 2680 KiB

Open AccessEditor’s ChoiceArticle

Anti-Cancer and Immunomodulatory Activity of a Polyethylene Glycol-Betulinic Acid Conjugate on Pancreatic Cancer Cells

by Pascaline Nanga Fru, Ekene Emmanuel Nweke, Nompumelelo Mthimkhulu, Sindisiwe Mvango, Marietha Nel, Lynne Alison Pilcher and Mohammed Balogun

Life 2021, 11(6), 462; https://doi.org/10.3390/life11060462 - 21 May 2021

Cited by 4 | Viewed by 2164

Abstract

Drug delivery systems involving polymer therapeutics enhance drug potency by improved solubility and specificity and may assist in circumventing chemoresistance in pancreatic cancer (PC). We compared the effectiveness of the naturally occurring drug, betulinic acid (BA), alone and in a polymer conjugate construct [...] Read more.

Drug delivery systems involving polymer therapeutics enhance drug potency by improved solubility and specificity and may assist in circumventing chemoresistance in pancreatic cancer (PC). We compared the effectiveness of the naturally occurring drug, betulinic acid (BA), alone and in a polymer conjugate construct of polyethylene glycol (PEG), (PEG–BA), on PC cells (MIA PaCa-2), a normal cell line (Vero) and on peripheral blood mononuclear cells (PBMCs). PEG–BA, was tested for its effect on cell death, immunomodulation and chemoresistance-linked signalling pathways. The conjugate was significantly more toxic to PC cells (p < 0.001, IC₅₀ of 1.35 ± 0.11 µM) compared to BA (IC₅₀ of 12.70 ± 0.34 µM), with a selectivity index (SI) of 7.28 compared to 1.4 in Vero cells. Cytotoxicity was confirmed by increased apoptotic cell death. PEG–BA inhibited the production of IL-6 by 4–5.5 fold compared to BA-treated cells. Furthermore, PEG–BA treatment of MIA PaCa-2 cells resulted in the dysregulation of crucial chemoresistance genes such as WNT3A, TXNRD1, SLC2A1 and GATA3. The dysregulation of chemoresistance-associated genes and the inhibition of cytokines such as IL-6 by the model polymer construct, PEG–BA, holds promise for further exploration in PC treatment. Full article

(This article belongs to the Special Issue Immune Reconstitution Disorders)

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28 pages, 3121 KiB

Open AccessEditor’s ChoiceReview

The “Water Problem”(sic), the Illusory Pond and Life’s Submarine Emergence—A Review

by Michael J. Russell

Life 2021, 11(5), 429; https://doi.org/10.3390/life11050429 - 10 May 2021

Cited by 19 | Viewed by 6255

Abstract

The assumption that there was a “water problem” at the emergence of life—that the Hadean Ocean was simply too wet and salty for life to have emerged in it—is here subjected to geological and experimental reality checks. The “warm little pond” that would [...] Read more.

The assumption that there was a “water problem” at the emergence of life—that the Hadean Ocean was simply too wet and salty for life to have emerged in it—is here subjected to geological and experimental reality checks. The “warm little pond” that would take the place of the submarine alkaline vent theory (AVT), as recently extolled in the journal Nature, flies in the face of decades of geological, microbiological and evolutionary research and reasoning. To the present author, the evidence refuting the warm little pond scheme is overwhelming given the facts that (i) the early Earth was a water world, (ii) its all-enveloping ocean was never less than 4 km deep, (iii) there were no figurative “Icelands” or “Hawaiis”, nor even an “Ontong Java” then because (iv) the solidifying magma ocean beneath was still too mushy to support such salient loadings on the oceanic crust. In place of the supposed warm little pond, we offer a well-protected mineral mound precipitated at a submarine alkaline vent as life’s womb: in place of lipid membranes, we suggest peptides; we replace poisonous cyanide with ammonium and hydrazine; instead of deleterious radiation we have the appropriate life-giving redox and pH disequilibria; and in place of messy chemistry we offer the potential for life’s emergence from the simplest of geochemically available molecules and ions focused at a submarine alkaline vent in the Hadean—specifically within the nano-confined flexible and redox active interlayer walls of the mixed-valent double layer oxyhydroxide mineral, fougerite/green rust comprising much of that mound. Full article

(This article belongs to the Collection Feature Review Papers for Life)

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15 pages, 1087 KiB

Open AccessEditor’s ChoiceReview

Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases

by Giuseppe Bellastella, Maria Ida Maiorino, Lorenzo Scappaticcio, Annamaria De Bellis, Silvia Mercadante, Katherine Esposito and Antonio Bellastella

Life 2021, 11(5), 426; https://doi.org/10.3390/life11050426 - 10 May 2021

Cited by 8 | Viewed by 2916

Abstract

Chronobiology is the scientific discipline which considers biological phenomena in relation to time, which assumes itself biological identity. Many physiological processes are cyclically regulated by intrinsic clocks and many pathological events show a circadian time-related occurrence. Even the pituitary–thyroid axis is under the [...] Read more.

Chronobiology is the scientific discipline which considers biological phenomena in relation to time, which assumes itself biological identity. Many physiological processes are cyclically regulated by intrinsic clocks and many pathological events show a circadian time-related occurrence. Even the pituitary–thyroid axis is under the control of a central clock, and the hormones of the pituitary–thyroid axis exhibit circadian, ultradian and circannual rhythmicity. This review, after describing briefly the essential principles of chronobiology, will be focused on the results of personal experiences and of other studies on this issue, paying particular attention to those regarding the thyroid implications, appearing in the literature as reviews, metanalyses, original and observational studies until 28 February 2021 and acquired from two databases (Scopus and PubMed). The first input to biological rhythms is given by a central clock located in the suprachiasmatic nucleus (SCN), which dictates the timing from its hypothalamic site to satellite clocks that contribute in a hierarchical way to regulate the physiological rhythmicity. Disruption of the rhythmic organization can favor the onset of important disorders, including thyroid diseases. Several studies on the interrelationship between thyroid function and circadian rhythmicity demonstrated that thyroid dysfunctions may affect negatively circadian organization, disrupting TSH rhythm. Conversely, alterations of clock machinery may cause important perturbations at the cellular level, which may favor thyroid dysfunctions and also cancer. Full article

(This article belongs to the Collection Feature Review Papers for Life)

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22 pages, 3353 KiB

Open AccessEditor’s ChoiceArticle

Loose Ends in the Cortinarius Phylogeny: Five New Myxotelamonoid Species Indicate a High Diversity of These Ectomycorrhizal Fungi with South American Nothofagaceae

by María Eugenia Salgado Salomón, Carolina Barroetaveña, Tuula Niskanen, Kare Liimatainen, Matthew E. Smith and Ursula Peintner

Life 2021, 11(5), 420; https://doi.org/10.3390/life11050420 - 05 May 2021

Cited by 4 | Viewed by 2734

Abstract

This paper is a contribution to the current knowledge of taxonomy, ecology and distribution of South American Cortinarius (Pers.) Gray. Cortinarius is among the most widely distributed and species-rich basidiomycete genera occurring with South American Nothofagaceae and species are found in many distinct [...] Read more.

This paper is a contribution to the current knowledge of taxonomy, ecology and distribution of South American Cortinarius (Pers.) Gray. Cortinarius is among the most widely distributed and species-rich basidiomycete genera occurring with South American Nothofagaceae and species are found in many distinct habitats, including shrublands and forests. Due to their ectomycorrhizal role, Cortinarius species are critical for nutrient cycling in forests, especially at higher latitudes. Some species have also been reported as edible fungi with high nutritional quality. Our aim is to unravel the taxonomy of selected Cortinarius belonging to phlegmacioid and myxotelamonioid species based on morphological and molecular data. After widely sampling Cortinarius specimens in Patagonian Nothofagaceae forests and comparing them to reference collections (including holotypes), we propose five new species of Cortinarius in this work. Phylogenetic analyses of concatenated rDNA ITS-LSU and RPB1 sequences failed to place these new species into known Cortinarius sections or lineages. These findings highlight our knowledge gaps regarding the fungal diversity of South American Nothofagaceae forests. Due to the high diversity of endemic Patagonian taxa, it is clear that the South American Cortinarius diversity needs to be discovered and described in order to understand the evolutionary history of Cortinarius on a global scale. Full article

(This article belongs to the Special Issue Biodiversity and Ecology of Fungi in Terrestrial and Marine Ecosystems)

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16 pages, 1458 KiB

Open AccessEditor’s ChoiceReview

Chronic Kidney Disease as a Systemic Inflammatory Syndrome: Update on Mechanisms Involved and Potential Treatment

by Francesca Tinti, Silvia Lai, Annalisa Noce, Silverio Rotondi, Giulia Marrone, Sandro Mazzaferro, Nicola Di Daniele and Anna Paola Mitterhofer

Life 2021, 11(5), 419; https://doi.org/10.3390/life11050419 - 05 May 2021

Cited by 46 | Viewed by 5080

Abstract

Chronic kidney disease (CKD) is characterized by manifestations and symptoms involving systemic organs and apparatus, associated with elevated cardiovascular morbidity and mortality, bone disease, and other tissue involvement. Arterial hypertension (AH), diabetes mellitus (DM), and dyslipidemia, with glomerular or congenital diseases, are the [...] Read more.

Chronic kidney disease (CKD) is characterized by manifestations and symptoms involving systemic organs and apparatus, associated with elevated cardiovascular morbidity and mortality, bone disease, and other tissue involvement. Arterial hypertension (AH), diabetes mellitus (DM), and dyslipidemia, with glomerular or congenital diseases, are the traditional risk factors recognized as the main causes of progressive kidney dysfunction evolving into uremia. Acute kidney injury (AKI) has recently been considered an additional risk factor for the worsening of CKD or the development of CKD de novo. Evidence underlies the role of systemic inflammation as a linking factor between AKI and CKD, recognizing the role of inflammation in AKI evolution to CKD. Moreover, abnormal increases in oxidative stress (OS) and inflammatory status in CKD seem to exert an important pathogenetic role, with significant involvement in the clinical management of this condition. With our revision, we want to focus on and update the inflammatory mechanisms responsible for the pathologic conditions associated with CKD, with particular attention on the development of AKI and AKI-CKD de novo, the alteration of calcium-phosphorus metabolism with bone disease and CKD-MBD syndrome, the status of malnutrition and malnutrition–inflammation complex syndrome (MICS) and protein-energy wasting (PEW), uremic sarcopenia, the status of OS, and the different inflammatory pathways, highlighting a new approach to CKD. The depth comprehension of the mechanisms underlying the development of inflammation in CKD may present new possible therapeutic approaches in CKD and hopefully improve the management of correlated morbidities and provide a reduction in associated mortality. Full article

(This article belongs to the Collection Research Updates in Chronic Kidney Disease)

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21 pages, 9239 KiB

Open AccessEditor’s ChoiceArticle

Molecular Insights into the Genetic Variability of ORF Virus in a Mediterranean Region (Sardinia, Italy)

by Elisabetta Coradduzza, Daria Sanna, Angela M. Rocchigiani, Davide Pintus, Fabio Scarpa, Rosario Scivoli, Roberto Bechere, Maria A. Dettori, Maria A. Montesu, Vincenzo Marras, Renato Lobrano, Ciriaco Ligios and Giantonella Puggioni

Life 2021, 11(5), 416; https://doi.org/10.3390/life11050416 - 04 May 2021

Cited by 8 | Viewed by 2292

Abstract

Orf virus (ORFV) represents the causative agent of contagious ecthyma, clinically characterized by mild papular and pustular to severe proliferative lesions, mainly occurring in sheep and goats. In order to provide hints on the evolutionary history of this virus, we carried out a [...] Read more.

Orf virus (ORFV) represents the causative agent of contagious ecthyma, clinically characterized by mild papular and pustular to severe proliferative lesions, mainly occurring in sheep and goats. In order to provide hints on the evolutionary history of this virus, we carried out a study aimed to assess the genetic variation of ORFV in Sardinia that hosts a large affected small ruminant population. We also found a high worldwide mutational viral evolutionary rate, which resulted, in turn, higher than the rate we detected for the strains isolated in Sardinia. In addition, a well-supported genetic divergence was found between the viral strains isolated from sheep and those from goats, but no relevant connection was evidenced between the severity of lesions produced by ORFV and specific polymorphic patterns in the two species of hosts. Such a finding suggests that ORFV infection-related lesions are not necessarily linked to the expression of one of the three genes here analyzed and could rather be the effect of the expression of other genes or rather represents a multifactorial character. Full article

(This article belongs to the Special Issue Evolutionary and Conservation Genetics)

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13 pages, 3197 KiB

Open AccessEditor’s ChoiceArticle

The Mitochondrial Genome of the Sea Anemone Stichodactyla haddoni Reveals Catalytic Introns, Insertion-Like Element, and Unexpected Phylogeny

by Steinar Daae Johansen, Sylvia I. Chi, Arseny Dubin and Tor Erik Jørgensen

Life 2021, 11(5), 402; https://doi.org/10.3390/life11050402 - 28 Apr 2021

Cited by 5 | Viewed by 3212

Abstract

A hallmark of sea anemone mitochondrial genomes (mitogenomes) is the presence of complex catalytic group I introns. Here, we report the complete mitogenome and corresponding transcriptome of the carpet sea anemone Stichodactyla haddoni (family Stichodactylidae). The mitogenome is vertebrate-like in size, organization, and [...] Read more.

A hallmark of sea anemone mitochondrial genomes (mitogenomes) is the presence of complex catalytic group I introns. Here, we report the complete mitogenome and corresponding transcriptome of the carpet sea anemone Stichodactyla haddoni (family Stichodactylidae). The mitogenome is vertebrate-like in size, organization, and gene content. Two mitochondrial genes encoding NADH dehydrogenase subunit 5 (ND5) and cytochrome c oxidase subunit I (COI) are interrupted with complex group I introns, and one of the introns (ND5-717) harbors two conventional mitochondrial genes (ND1 and ND3) within its sequence. All the mitochondrial genes, including the group I introns, are expressed at the RNA level. Nonconventional and optional mitochondrial genes are present in the mitogenome of S. haddoni. One of these gene codes for a COI-884 intron homing endonuclease and is organized in-frame with the upstream COI exon. The insertion-like orfA is expressed as RNA and translocated in the mitogenome as compared with other sea anemones. Phylogenetic analyses based on complete nucleotide and derived protein sequences indicate that S. haddoni is embedded within the family Actiniidae, a finding that challenges current taxonomy. Full article

(This article belongs to the Special Issue Molecular Phylogenetics and Mitochondrial Evolution)

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38 pages, 6064 KiB

Open AccessEditor’s ChoiceReview

Proton Bridging in Catalysis by and Inhibition of Serine Proteases of the Blood Cascade System

by Ildiko M Kovach

Life 2021, 11(5), 396; https://doi.org/10.3390/life11050396 - 27 Apr 2021

Cited by 2 | Viewed by 2676

Abstract

Inquiries into the participation of short hydrogen bonds in stabilizing transition states and intermediate states in the thrombin, factor Xa, plasmin and activated protein C–catalyzed reactions revealed that specific binding of effectors at S_n, n = 1–4 and S’_n, [...] Read more.

Inquiries into the participation of short hydrogen bonds in stabilizing transition states and intermediate states in the thrombin, factor Xa, plasmin and activated protein C–catalyzed reactions revealed that specific binding of effectors at S_n, n = 1–4 and S’_n, n = 1–3 and at remote exosites elicit complex patterns of hydrogen bonding and involve water networks. The methods employed that yielded these discoveries include; (1) kinetics, especially partial or full kinetic deuterium solvent isotope effects with short cognate substrates and also with the natural substrates, (2) kinetic and structural probes, particularly low-field high-resolution nuclear magnetic resonance (¹H NMR), of mechanism-based inhibitors and substrate-mimic peptide inhibitors. Short hydrogen bonds form at the transition states of the catalytic reactions at the active site of the enzymes as they do with mechanism-based covalent inhibitors of thrombin. The emergence of short hydrogen bonds at the binding interface of effectors and thrombin at remote exosites has recently gained recognition. Herein, I describe our contribution, a confirmation of this discovery, by low-field ¹H NMR. The principal conclusion of this review is that proton sharing at distances below the sum of van der Waals radii of the hydrogen and both donor and acceptor atoms contribute to the remarkable catalytic prowess of serine proteases of the blood clotting system and other enzymes that employ acid-base catalysis. Proton bridges also play a role in tight binding in proteins and at exosites, i.e., allosteric sites, of enzymes. Full article

(This article belongs to the Special Issue Current Approaches in Molecular Enzymology)

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21 pages, 1586 KiB

Open AccessEditor’s ChoiceReview

Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside

by Sungjin Chung and Gheun-Ho Kim

Life 2021, 11(5), 389; https://doi.org/10.3390/life11050389 - 25 Apr 2021

Cited by 7 | Viewed by 4419

Abstract

New drugs were recently developed to treat hyperglycemia in patients with type 2 diabetes mellitus (T2D). However, metformin remains the first-line anti-diabetic agent because of its cost-effectiveness. It has pleiotropic action that produces cardiovascular benefits, and it can be useful in diabetic nephropathy, [...] Read more.

New drugs were recently developed to treat hyperglycemia in patients with type 2 diabetes mellitus (T2D). However, metformin remains the first-line anti-diabetic agent because of its cost-effectiveness. It has pleiotropic action that produces cardiovascular benefits, and it can be useful in diabetic nephropathy, although metformin-associated lactic acidosis is a hindrance to its use in patients with kidney failure. New anti-diabetic agents, including glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors, also produce cardiovascular or renal benefits in T2D patients. Their glucose-independent beneficial actions can lead to cardiorenal protection via hemodynamic stabilization and inflammatory modulation. Systemic hypertension is relieved by natriuresis and improved vascular dysfunction. Enhanced tubuloglomerular feedback can be restored by SGLT-2 inhibition, reducing glomerular hypertension. Patients with non-diabetic kidney disease might also benefit from those drugs because hypertension, proteinuria, oxidative stress, and inflammation are common factors in the progression of kidney disease, irrespective of the presence of diabetes. In various animal models of non-diabetic kidney disease, metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors were favorable to kidney morphology and function. They strikingly attenuated biomarkers of oxidative stress and inflammatory responses in diseased kidneys. However, whether those animal results translate to patients with non-diabetic kidney disease has yet to be evaluated. Considering the paucity of new agents to treat kidney disease and the minimal adverse effects of metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors, these anti-diabetic agents could be used in patients with non-diabetic kidney disease. This paper provides a rationale for clinical trials that apply metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors to non-diabetic kidney disease. Full article

(This article belongs to the Collection Research Updates in Chronic Kidney Disease)

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11 pages, 288 KiB

Open AccessEditor’s ChoiceReview

Impact of Exercise Intensity on Calprotectin Levels in Healthy Volunteers and Patients with Inflammatory Rheumatic Diseases

by Andy Xavier and Annabelle Cesaro

Life 2021, 11(5), 377; https://doi.org/10.3390/life11050377 - 22 Apr 2021

Viewed by 2188

Abstract

Exercise influences inflammatory response and immune system performance. The regular practice of a moderate activity positively regulates immunity and the inflammatory process, while intensive training depresses it and enhances inflammatory marker secretion. Calprotectin is involved in the inflammatory process, promoting neutrophil recruitment, cell [...] Read more.

Exercise influences inflammatory response and immune system performance. The regular practice of a moderate activity positively regulates immunity and the inflammatory process, while intensive training depresses it and enhances inflammatory marker secretion. Calprotectin is involved in the inflammatory process, promoting neutrophil recruitment, cell degranulation, and inflammatory mediators. Furthermore, calprotectin has been associated with various inflammatory diseases, including inflammatory rheumatic diseases. The present review explores the effect of exercise on calprotectin levels in both healthy and inflammatory rheumatic conditions. Data show that the intensity duration and the type of exercise modulate calprotectin levels and participant inflammatory status. The exact role of calprotectin in the exercise response is yet unknown. Calprotectin could constitute an interesting biomarker for monitoring both the effect of exercise on the inflammatory process in healthy volunteers and the efficiency of exercise treatment programs in a patient with inflammatory rheumatic disease. Full article

(This article belongs to the Special Issue Impact of Physical Exercises on Bone Activities)

7 pages, 5284 KiB

Open AccessEditor’s ChoiceReview

The Three Pillars of COVID-19 Convalescent Plasma Therapy

by Massimo Franchini, Giancarlo Maria Liumbruno, Giorgio Piacentini, Claudia Glingani and Marco Zaffanello

Life 2021, 11(4), 354; https://doi.org/10.3390/life11040354 - 18 Apr 2021

Cited by 16 | Viewed by 2844

Abstract

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread rapidly around the world in the last year causing the coronavirus disease 2019 (COVID-19), which still is a severe threat for public health. The therapeutic management of COVID-19 is challenging as, [...] Read more.

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread rapidly around the world in the last year causing the coronavirus disease 2019 (COVID-19), which still is a severe threat for public health. The therapeutic management of COVID-19 is challenging as, up until now, no specific and efficient pharmacological therapy has been validated. Translating the experience from previous viral epidemics, passive immunotherapy by means of plasma from individuals recovered from COVID-19 has been intensively investigated since the beginning of the pandemic. In this narrative review, we critically analyze the three factors, named “pillars”, that play a key role in determining the clinical effectiveness of this biologic therapy: the convalescent plasma, the disease (COVID-19), and the patients. Full article

(This article belongs to the Special Issue Neutralizing-Antibody-Based Treatments for COVID-19: Achievements and Lessons Learnt for Future Pandemics)

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20 pages, 7513 KiB

Open AccessEditor’s ChoiceReview

The “Genomic Code”: DNA Pervasively Moulds Chromatin Structures Leaving no Room for “Junk”

by Giorgio Bernardi

Life 2021, 11(4), 342; https://doi.org/10.3390/life11040342 - 13 Apr 2021

Cited by 6 | Viewed by 3141

Abstract

The chromatin of the human genome was analyzed at three DNA size levels. At the first, compartment level, two “gene spaces” were found many years ago: A GC-rich, gene-rich “genome core” and a GC-poor, gene-poor “genome desert”, the former corresponding to open chromatin [...] Read more.

The chromatin of the human genome was analyzed at three DNA size levels. At the first, compartment level, two “gene spaces” were found many years ago: A GC-rich, gene-rich “genome core” and a GC-poor, gene-poor “genome desert”, the former corresponding to open chromatin centrally located in the interphase nucleus, the latter to closed chromatin located peripherally. This bimodality was later confirmed and extended by the discoveries (1) of LADs, the Lamina-Associated Domains, and InterLADs; (2) of two “spatial compartments”, A and B, identified on the basis of chromatin interactions; and (3) of “forests and prairies” characterized by high and low CpG islands densities. Chromatin compartments were shown to be associated with the compositionally different, flat and single- or multi-peak DNA structures of the two, GC-poor and GC-rich, “super-families” of isochores. At the second, sub-compartment, level, chromatin corresponds to flat isochores and to isochore loops (due to compositional DNA gradients) that are susceptible to extrusion. Finally, at the short-sequence level, two sets of sequences, GC-poor and GC-rich, define two different nucleosome spacings, a short one and a long one. In conclusion, chromatin structures are moulded according to a “genomic code” by DNA sequences that pervade the genome and leave no room for “junk”. Full article

(This article belongs to the Collection Feature Review Papers for Life)

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21 pages, 2131 KiB

Open AccessEditor’s ChoiceReview

Theranostics in Boron Neutron Capture Therapy

by Wolfgang A. G. Sauerwein, Lucie Sancey, Evamarie Hey-Hawkins, Martin Kellert, Luigi Panza, Daniela Imperio, Marcin Balcerzyk, Giovanna Rizzo, Elisa Scalco, Ken Herrmann, PierLuigi Mauri, Antonella De Palma and Andrea Wittig

Life 2021, 11(4), 330; https://doi.org/10.3390/life11040330 - 10 Apr 2021

Cited by 32 | Viewed by 4930

Abstract

Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: ¹⁰B [...] Read more.

Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: ¹⁰B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of ¹⁰B in the tumor but also on the organs at risk. It is not yet possible to determine the ¹⁰B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the ¹⁰B concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake of ¹⁰B from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine the ¹⁰B concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach. Full article

(This article belongs to the Special Issue Theranostics: Current and Future Perspectives)

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9 pages, 1134 KiB

Open AccessEditor’s ChoiceArticle

Long Noncoding RNA NEAT1 as a Potential Candidate Biomarker for Prostate Cancer

by Diana Nitusca, Anca Marcu, Alis Dema, Loredana Balacescu, Ovidiu Balacescu, Razvan Bardan, Alin Adrian Cumpanas, Ioan Ovidiu Sirbu, Bogdan Petrut, Edward Seclaman and Catalin Marian

Life 2021, 11(4), 320; https://doi.org/10.3390/life11040320 - 06 Apr 2021

Cited by 9 | Viewed by 2414

Abstract

Background: Prostate cancer (PCa) remains one of the leading causes of cancer-related mortality in men worldwide, mainly due to unsatisfactory diagnostic methods used at present, which lead to overdiagnosis, unnecessary biopsies and treatment, or misdiagnosis in early asymptomatic stages. New diagnostic biomarkers are [...] Read more.

Background: Prostate cancer (PCa) remains one of the leading causes of cancer-related mortality in men worldwide, mainly due to unsatisfactory diagnostic methods used at present, which lead to overdiagnosis, unnecessary biopsies and treatment, or misdiagnosis in early asymptomatic stages. New diagnostic biomarkers are needed for a correct and early diagnosis. Long noncoding RNAs (lncRNAs) have been broadly studied for their involvement in PCa biology, as well as for their potential role as diagnostic biomarkers. Methods: We conducted lncRNA profiling in plasma and microdissected formalin-fixed paraffin-embedded (FFPE) tissues of PCa patients and attempted validation for commonly dysregulated individual lncRNAs. Results: Plasma profiling revealed eight dysregulated lncRNAs, while microarray analysis revealed 717 significantly dysregulated lncRNAs, out of which only nuclear-enriched abundant transcript 1 (NEAT1) was commonly upregulated in plasma samples and FFPE tissues. NEAT1’s individual validation revealed statistically significant upregulation (FC = 2.101, p = 0.009). Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) value of 0.7298 for NEAT1 (95% CI = 0.5812–0.8785), suggesting a relatively high diagnostic value, thus having a potential biomarker role for this malignancy. Conclusions: We present herein data suggesting that NEAT1 could serve as a diagnostic biomarker for PCa. Additional studies of larger cohorts are needed to confirm our findings, as well as the oncogenic mechanism of NEAT1 in the development of PCa. Full article

(This article belongs to the Special Issue Prostate Cancer)

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12 pages, 1809 KiB

Open AccessEditor’s ChoiceArticle

Transcription Factor Activity Inference in Systemic Lupus Erythematosus

by Raul Lopez-Dominguez, Daniel Toro-Dominguez, Jordi Martorell-Marugan, Adrian Garcia-Moreno, Christian H. Holland, Julio Saez-Rodriguez, Daniel Goldman, Michelle A. Petri, Marta E. Alarcon-Riquelme and Pedro Carmona-Saez

Life 2021, 11(4), 299; https://doi.org/10.3390/life11040299 - 01 Apr 2021

Cited by 5 | Viewed by 3287

Abstract

Background: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with diverse clinical manifestations. Although most of the SLE-associated loci are located in regulatory regions, there is a lack of global information about transcription factor (TFs) activities, the mode of regulation of the [...] Read more.

Background: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with diverse clinical manifestations. Although most of the SLE-associated loci are located in regulatory regions, there is a lack of global information about transcription factor (TFs) activities, the mode of regulation of the TFs, or the cell or sample-specific regulatory circuits. The aim of this work is to decipher TFs implicated in SLE. Methods: In order to decipher regulatory mechanisms in SLE, we have inferred TF activities from transcriptomic data for almost all human TFs, defined clusters of SLE patients based on the estimated TF activities and analyzed the differential activity patterns among SLE and healthy samples in two different cohorts. The Transcription Factor activity matrix was used to stratify SLE patients and define sets of TFs with statistically significant differential activity among the disease and control samples. Results: TF activities were able to identify two main subgroups of patients characterized by distinct neutrophil-to-lymphocyte ratio (NLR), with consistent patterns in two independent datasets—one from pediatric patients and other from adults. Furthermore, after contrasting all subgroups of patients and controls, we obtained a significant and robust list of 14 TFs implicated in the dysregulation of SLE by different mechanisms and pathways. Among them, well-known regulators of SLE, such as STAT or IRF, were found, but others suggest new pathways that might have important roles in SLE. Conclusions: These results provide a foundation to comprehend the regulatory mechanism underlying SLE and the established regulatory factors behind SLE heterogeneity that could be potential therapeutic targets. Full article

(This article belongs to the Special Issue Genomics and Epigenomics of Human Complex Diseases)

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21 pages, 3019 KiB

Open AccessEditor’s ChoiceArticle

Priming by High Temperature Stress Induces MicroRNA Regulated Heat Shock Modules Indicating Their Involvement in Thermopriming Response in Rice

by Akhilesh Kumar Kushawaha, Ambreen Khan, Sudhir Kumar Sopory and Neeti Sanan-Mishra

Life 2021, 11(4), 291; https://doi.org/10.3390/life11040291 - 29 Mar 2021

Cited by 20 | Viewed by 4109

Abstract

Rice plants often encounter high temperature stress, but the associated coping strategies are poorly understood. It is known that a prior shorter exposure to high temperature, called thermo-priming, generally results in better adaptation of the plants to subsequent exposure to high temperature stress. [...] Read more.

Rice plants often encounter high temperature stress, but the associated coping strategies are poorly understood. It is known that a prior shorter exposure to high temperature, called thermo-priming, generally results in better adaptation of the plants to subsequent exposure to high temperature stress. High throughput sequencing of transcript and small RNA libraries of rice seedlings primed with short exposure to high temperature followed by high temperature stress and from plants exposed to high temperature without priming was performed. This identified a number of transcripts and microRNAs (miRs) that are induced or down regulated. Among them osa-miR531b, osa-miR5149, osa-miR168a-5p, osa-miR1846d-5p, osa-miR5077, osa-miR156b-3p, osa-miR167e-3p and their respective targets, coding for heat shock activators and repressors, showed differential expression between primed and non-primed plants. These findings were further validated by qRT-PCR. The results indicate that the miR-regulated heat shock proteins (HSPs)/heat shock transcription factors (HSFs) may serve as important regulatory nodes which are induced during thermo-priming for plant survival and development under high temperatures. Full article

(This article belongs to the Special Issue Research Advances in Plant Genomics)

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21 pages, 2371 KiB

Open AccessEditor’s ChoiceReview

MicroRNAs: Potential Targets for Developing Stress-Tolerant Crops

by Saurabh Chaudhary, Atul Grover and Prakash Chand Sharma

Life 2021, 11(4), 289; https://doi.org/10.3390/life11040289 - 28 Mar 2021

Cited by 21 | Viewed by 7548

Abstract

Crop yield is challenged every year worldwide by changing climatic conditions. The forecasted climatic scenario urgently demands stress-tolerant crop varieties to feed the ever-increasing global population. Molecular breeding and genetic engineering approaches have been frequently exploited for developing crops with desired agronomic traits. [...] Read more.

Crop yield is challenged every year worldwide by changing climatic conditions. The forecasted climatic scenario urgently demands stress-tolerant crop varieties to feed the ever-increasing global population. Molecular breeding and genetic engineering approaches have been frequently exploited for developing crops with desired agronomic traits. Recently, microRNAs (miRNAs) have emerged as powerful molecules, which potentially serve as expression markers during stress conditions. The miRNAs are small non-coding endogenous RNAs, usually 20–24 nucleotides long, which mediate post-transcriptional gene silencing and fine-tune the regulation of many abiotic- and biotic-stress responsive genes in plants. The miRNAs usually function by specifically pairing with the target mRNAs, inducing their cleavage or repressing their translation. This review focuses on the exploration of the functional role of miRNAs in regulating plant responses to abiotic and biotic stresses. Moreover, a methodology is also discussed to mine stress-responsive miRNAs from the enormous amount of transcriptome data available in the public domain generated using next-generation sequencing (NGS). Considering the functional role of miRNAs in mediating stress responses, these molecules may be explored as novel targets for engineering stress-tolerant crop varieties. Full article

(This article belongs to the Special Issue Metabolism of Photosynthetic Organisms)

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15 pages, 2586 KiB

Open AccessEditor’s ChoiceArticle

SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma

by Marius-Alexandru Beleaua, Ioan Jung, Cornelia Braicu, Doina Milutin and Simona Gurzu

Life 2021, 11(4), 281; https://doi.org/10.3390/life11040281 - 27 Mar 2021

Cited by 8 | Viewed by 2858

Abstract

Malignant melanoma (MM) is a highly heterogenic tumor whose histological diagnosis might be difficult. This study aimed to investigate the diagnostic and prognostic utility of the conventional pan-melanoma cocktail members (HMB-45, melan-A and tyrosinase), in conjunction with SOX10 and SOX11 immunohistochemical (IHC) expression. [...] Read more.

Malignant melanoma (MM) is a highly heterogenic tumor whose histological diagnosis might be difficult. This study aimed to investigate the diagnostic and prognostic utility of the conventional pan-melanoma cocktail members (HMB-45, melan-A and tyrosinase), in conjunction with SOX10 and SOX11 immunohistochemical (IHC) expression. In 105 consecutive cases of MMs and 44 of naevi, the IHC examination was performed using the five-abovementioned markers, along with microphthalmia transcription factor (MITF), S100, and Ki67. Correlation with the clinicopathological factors and a long-term follow-up was also done. Survival analysis was performed with Kaplan–Meier curves and compared with TCGA public datasets. None of the 44 naevi expressed SOX11, but its positivity was seen in 52 MMs (49.52%), being directly correlated with lymphovascular invasion, the Ki67 index, and SOX10 expression. HMB-45, SOX10, and tyrosinase, but not melan-A, proved to differentiate the naevi from MMs successfully, with high specificity. Triple MITF/SOX10/SOX11 co-expression was seen in 9 out of 15 negative conventional pan-melanoma-cocktail cases. The independent prognostic value was proved for the conventional pan-melanoma cocktail (triple positivity for HMB-45, melan-A, and tyrosinase) and, independently for HMB-45 and tyrosinase, but not for melan-A, SOX10, or SOX11. As consequence, to differentiate MMs from benign naevi, melan-A should be substituted by SOX10 in the conventional cocktail. Although the conventional pan-melanoma cocktail, along with S100 can be used for the identification of melanocytic origin of tumor cells and predicting prognosis of MMs, the conventional-adapted cocktail (triple positivity for HMB-45, SOX10, and tyrosinase) has a slightly higher diagnostic specificity. SOX11 can be added to identify the aggressive MMs with risk for lymphatic dissemination and the presence of circulating tumor cells. Full article

(This article belongs to the Special Issue Serum and Tissue Biomarkers in Cancer: A Translational Approach)

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20 pages, 20644 KiB

Open AccessEditor’s ChoiceArticle

Stability and Robustness of Unbalanced Genetic Toggle Switches in the Presence of Scarce Resources

by Chentao Yong and Andras Gyorgy

Life 2021, 11(4), 271; https://doi.org/10.3390/life11040271 - 24 Mar 2021

Cited by 4 | Viewed by 3124

Abstract

While the vision of synthetic biology is to create complex genetic systems in a rational fashion, system-level behaviors are often perplexing due to the context-dependent dynamics of modules. One major source of context-dependence emerges due to the limited availability of shared resources, coupling [...] Read more.

While the vision of synthetic biology is to create complex genetic systems in a rational fashion, system-level behaviors are often perplexing due to the context-dependent dynamics of modules. One major source of context-dependence emerges due to the limited availability of shared resources, coupling the behavior of disconnected components. Motivated by the ubiquitous role of toggle switches in genetic circuits ranging from controlling cell fate differentiation to optimizing cellular performance, here we reveal how their fundamental dynamic properties are affected by competition for scarce resources. Combining a mechanistic model with nullcline-based stability analysis and potential landscape-based robustness analysis, we uncover not only the detrimental impacts of resource competition, but also how the unbalancedness of the switch further exacerbates them. While in general both of these factors undermine the performance of the switch (by pushing the dynamics toward monostability and increased sensitivity to noise), we also demonstrate that some of the unwanted effects can be alleviated by strategically optimized resource competition. Our results provide explicit guidelines for the context-aware rational design of toggle switches to mitigate our reliance on lengthy and expensive trial-and-error processes, and can be seamlessly integrated into the computer-aided synthesis of complex genetic systems. Full article

(This article belongs to the Special Issue Trends and Outlooks in Synthetic Biology: A Special Issue for Celebrating 10 Years of Life and Its Landmarks)

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11 pages, 1597 KiB

Open AccessEditor’s ChoiceArticle

A Relationship between NTP and Cell Extract Concentration for Cell-Free Protein Expression

by Katsuki Takahashi, Gaku Sato, Nobuhide Doi and Kei Fujiwara

Life 2021, 11(3), 237; https://doi.org/10.3390/life11030237 - 13 Mar 2021

Cited by 9 | Viewed by 3211

Abstract

The cell-free protein synthesis (CFPS) that synthesizes mRNA and protein from a template DNA has been featured as an important tool to emulate living systems in vitro. However, an obstacle to emulate living cells by CFPS is the loss of activity in the [...] Read more.

The cell-free protein synthesis (CFPS) that synthesizes mRNA and protein from a template DNA has been featured as an important tool to emulate living systems in vitro. However, an obstacle to emulate living cells by CFPS is the loss of activity in the case of usage of high concentration cell extracts. In this study, we found that a high concentration of NTP which inhibits in the case of lower concentration cell extract restored the loss of CFPS activity using high concentration cell extracts. The NTP restoration was independent of the energy regeneration system used, and NTP derivatives also restored the levels of CFPS using a high concentration cell extract. Experiments using dialysis mode of CFPS showed that continuous exchange of small molecule reduced levels of NTP requirement and improved reaction speed of CFPS using the high concentration of cell extract. These findings contribute to the development of a method to understand the condition of living cells by in vitro emulation, and are expected to lead to the achievement of the reconstitution of living cells from biomolecule mixtures. Full article

(This article belongs to the Special Issue Trends and Outlooks in Synthetic Biology: A Special Issue for Celebrating 10 Years of Life and Its Landmarks)

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11 pages, 740 KiB

Open AccessEditor’s ChoiceArticle

Pro-Oxidant/Antioxidant Balance during a Prolonged Exposure to Moderate Altitude in Athletes Exhibiting Exercise-Induced Hypoxemia at Sea-Level

by Antoine Raberin, Elie Nader, Jorge Lopez Ayerbe, Gauthier Alfonsi, Patrick Mucci, Chantal L. Rytz, Vincent Pialoux and Fabienne Durand

Life 2021, 11(3), 228; https://doi.org/10.3390/life11030228 - 11 Mar 2021

Cited by 4 | Viewed by 2276

Abstract

This study examined to what extent athletes exhibiting exercise-induced hypoxemia (EIH) possess an altered redox status at rest, in response to exercise at sea level (SL) and during moderate altitude exposure. EIH was defined as a fall in arterial O₂ saturation of [...] Read more.

This study examined to what extent athletes exhibiting exercise-induced hypoxemia (EIH) possess an altered redox status at rest, in response to exercise at sea level (SL) and during moderate altitude exposure. EIH was defined as a fall in arterial O₂ saturation of at least 4% during exercise. Nine endurance athletes with EIH and ten without (NEIH) performed a maximal incremental test under three conditions: SL, one (H1) and five (H2) days after arrival to 2400 m. Gas exchange and peripheral capillary oxygen saturation (SpO₂) were continuously monitored. Blood was sampled before exercise and after exercise cessation. Advanced oxidation protein products (AOPP), catalase, ferric-reducing antioxidant power, glutathione peroxidase, superoxide dismutase (SOD) and nitric oxide metabolites (NOx) were measured in plasma by spectrophotometry. EIH athletes had higher AOPP and NOx concentrations at pre- and post-exercise stages compared to NEIH at SL, H2 but not at H1. Only the EIH group experienced increased SOD activity between pre- and post-exercise exercise at SL and H2 but not at H1. EIH athletes had exacerbated oxidative stress compared to the NEIH athletes at SL and H2. These differences were blunted at H1. Oxidative stress did not alter the EIH groups’ aerobic performance and could lead to higher minute ventilation at H2. These results suggest that higher oxidative stress response EIH athletes could be involved in improved aerobic muscle functionality and a greater ventilatory acclimatization during prolonged hypoxia. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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19 pages, 2501 KiB

Open AccessEditor’s ChoiceArticle

The Mitochondrial Genome of a Plant Fungal Pathogen Pseudocercospora fijiensis (Mycosphaerellaceae), Comparative Analysis and Diversification Times of the Sigatoka Disease Complex Using Fossil Calibrated Phylogenies

by Juliana E. Arcila-Galvis, Rafael E. Arango, Javier M. Torres-Bonilla and Tatiana Arias

Life 2021, 11(3), 215; https://doi.org/10.3390/life11030215 - 09 Mar 2021

Cited by 6 | Viewed by 2806

Abstract

Mycosphaerellaceae is a highly diverse fungal family containing a variety of pathogens affecting many economically important crops. Mitochondria play a crucial role in fungal metabolism and in the study of fungal evolution. This study aims to: (i) describe the mitochondrial genome of Pseudocercospora [...] Read more.

Mycosphaerellaceae is a highly diverse fungal family containing a variety of pathogens affecting many economically important crops. Mitochondria play a crucial role in fungal metabolism and in the study of fungal evolution. This study aims to: (i) describe the mitochondrial genome of Pseudocercospora fijiensis, and (ii) compare it with closely related species (Sphaerulina musiva, S. populicola, P. musae and P. eumusae) available online, paying particular attention to the Sigatoka disease’s complex causal agents. The mitochondrial genome of P. fijiensis is a circular molecule of 74,089 bp containing typical genes coding for the 14 proteins related to oxidative phosphorylation, 2 rRNA genes and a set of 38 tRNAs. P. fijiensis mitogenome has two truncated cox1 copies, and bicistronic transcription of nad2-nad3 and atp6-atp8 confirmed experimentally. Comparative analysis revealed high variability in size and gene order among selected Mycosphaerellaceae mitogenomes likely to be due to rearrangements caused by mobile intron invasion. Using fossil calibrated Bayesian phylogenies, we found later diversification times for Mycosphaerellaceae (66.6 MYA) and the Sigatoka disease complex causal agents, compared to previous strict molecular clock studies. An early divergent Pseudocercospora fijiensis split from the sister species P. musae + P. eumusae 13.31 MYA while their sister group, the sister species P. eumusae and P. musae, split from their shared common ancestor in the late Miocene 8.22 MYA. This newly dated phylogeny suggests that species belonging to the Sigatoka disease complex originated after wild relatives of domesticated bananas (section Eumusae; 27.9 MYA). During this time frame, mitochondrial genomes expanded significantly, possibly due to invasions of introns into different electron transport chain genes. Full article

(This article belongs to the Special Issue Molecular Phylogenetics and Mitochondrial Evolution)

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18 pages, 1796 KiB

Open AccessEditor’s ChoiceReview

Biosensors: A Sneak Peek into Plant Cell’s Immunity

by Valentina Levak, Tjaša Lukan, Kristina Gruden and Anna Coll

Life 2021, 11(3), 209; https://doi.org/10.3390/life11030209 - 07 Mar 2021

Cited by 3 | Viewed by 3364

Abstract

Biosensors are indispensable tools to understand a plant’s immunity as its spatiotemporal dimension is key in withstanding complex plant immune signaling. The diversity of genetically encoded biosensors in plants is expanding, covering new analytes with ever higher sensitivity and robustness, but their assortment [...] Read more.

Biosensors are indispensable tools to understand a plant’s immunity as its spatiotemporal dimension is key in withstanding complex plant immune signaling. The diversity of genetically encoded biosensors in plants is expanding, covering new analytes with ever higher sensitivity and robustness, but their assortment is limited in some respects, such as their use in following biotic stress response, employing more than one biosensor in the same chassis, and their implementation into crops. In this review, we focused on the available biosensors that encompass these aspects. We show that in vivo imaging of calcium and reactive oxygen species is satisfactorily covered with the available genetically encoded biosensors, while on the other hand they are still underrepresented when it comes to imaging of the main three hormonal players in the immune response: salicylic acid, ethylene and jasmonic acid. Following more than one analyte in the same chassis, upon one or more conditions, has so far been possible by using the most advanced genetically encoded biosensors in plants which allow the monitoring of calcium and the two main hormonal pathways involved in plant development, auxin and cytokinin. These kinds of biosensor are also the most evolved in crops. In the last section, we examine the challenges in the use of biosensors and demonstrate some strategies to overcome them. Full article

(This article belongs to the Special Issue Plant Synthetic Biology)

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17 pages, 5829 KiB

Open AccessEditor’s ChoiceArticle

Chronological Incongruences between Mitochondrial and Nuclear Phylogenies of Aedes Mosquitoes

by Nicola Zadra, Annapaola Rizzoli and Omar Rota-Stabelli

Life 2021, 11(3), 181; https://doi.org/10.3390/life11030181 - 25 Feb 2021

Cited by 12 | Viewed by 3053

Abstract

One-third of all mosquitoes belong to the Aedini, a tribe comprising common vectors of viral zoonoses such as Aedes aegypti and Aedes albopictus. To improve our understanding of their evolution, we present an updated multigene estimate of Aedini phylogeny and divergence, focusing [...] Read more.

One-third of all mosquitoes belong to the Aedini, a tribe comprising common vectors of viral zoonoses such as Aedes aegypti and Aedes albopictus. To improve our understanding of their evolution, we present an updated multigene estimate of Aedini phylogeny and divergence, focusing on the disentanglement between nuclear and mitochondrial phylogenetic signals. We first show that there are some phylogenetic discrepancies between nuclear and mitochondrial markers which may be caused by wrong taxa assignment in samples collections or by some stochastic effect due to small gene samples. We indeed show that the concatenated dataset is model and framework dependent, indicating a general paucity of signal. Our Bayesian calibrated divergence estimates point toward a mosquito radiation in the mid-Jurassic and an Aedes radiation from the mid-Cretaceous on. We observe, however a strong chronological incongruence between mitochondrial and nuclear data, the latter providing divergence times within the Aedini significantly younger than the former. We show that this incongruence is consistent over different datasets and taxon sampling and that may be explained by either peculiar evolutionary event such as different levels of saturation in certain lineages or a past history of hybridization throughout the genus. Overall, our updated picture of Aedini phylogeny, reveal a strong nuclear-mitochondrial incongruence which may be of help in setting the research agenda for future phylogenomic studies of Aedini mosquitoes. Full article

(This article belongs to the Special Issue Molecular Phylogenetics and Mitochondrial Evolution)

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9 pages, 263 KiB

Open AccessEditor’s ChoiceArticle

Metabolic Phenotypes and Chronic Kidney Disease: A Cross-Sectional Assessment of Patients from a Large Federally Qualified Health Center

by Kathleen E. Adair, Nicholas von Waaden, Matthew Rafalski, Burritt W. Hess, Sally P. Weaver and Rodney G. Bowden

Life 2021, 11(2), 175; https://doi.org/10.3390/life11020175 - 23 Feb 2021

Cited by 7 | Viewed by 2411

Abstract

The purpose of this study is to determine if renal function varies by metabolic phenotype. A total of 9599 patients from a large Federally Qualified Health Center (FQHC) were included in the analysis. Metabolic health was classified as the absence of metabolic abnormalities [...] Read more.

The purpose of this study is to determine if renal function varies by metabolic phenotype. A total of 9599 patients from a large Federally Qualified Health Center (FQHC) were included in the analysis. Metabolic health was classified as the absence of metabolic abnormalities defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, excluding waist circumference. Obesity was defined as body mass index >30 kg/m² and renal health as an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m². Linear and logistic regressions were used to analyze the data. The metabolically healthy overweight (MHO) phenotype had the highest eGFR (104.86 ± 28.76 mL/min/1.72 m²) and lowest unadjusted odds of chronic kidney disease (CKD) (OR = 0.46, 95%CI = 0.168, 1.267, p = 0.133), while the metabolically unhealthy normal weight (MUN) phenotype demonstrated the lowest eGFR (91.34 ± 33.28 mL/min/1.72 m²) and the highest unadjusted odds of CKD (OR = 3.63, p < 0.0001). After controlling for age, sex, and smoking status, the metabolically unhealthy obese (MUO) (OR = 1.80, 95%CI = 1.08, 3.00, p = 0.024) was the only phenotype with significantly higher odds of CKD as compared to the reference. We demonstrate that the metabolically unhealthy phenotypes have the highest odds of CKD compared to metabolically healthy individuals. Full article

(This article belongs to the Collection Research Updates in Chronic Kidney Disease)

16 pages, 1354 KiB

Open AccessEditor’s ChoiceReview

Post-Infectious Guillain–Barré Syndrome Related to SARS-CoV-2 Infection: A Systematic Review

by Pasquale Sansone, Luca Gregorio Giaccari, Caterina Aurilio, Francesco Coppolino, Valentina Esposito, Marco Fiore, Antonella Paladini, Maria Beatrice Passavanti, Vincenzo Pota and Maria Caterina Pace

Life 2021, 11(2), 167; https://doi.org/10.3390/life11020167 - 21 Feb 2021

Cited by 27 | Viewed by 3620

Abstract

Background. Guillain-Barré syndrome (GBS) is the most common cause of flaccid paralysis, with about 100,000 people developing the disorder every year worldwide. Recently, the incidence of GBS has increased during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemics. We reviewed the literature to [...] Read more.

Background. Guillain-Barré syndrome (GBS) is the most common cause of flaccid paralysis, with about 100,000 people developing the disorder every year worldwide. Recently, the incidence of GBS has increased during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemics. We reviewed the literature to give a comprehensive overview of the demographic characteristics, clinical features, diagnostic investigations, and outcome of SARS-CoV-2-related GBS patients. Methods. Embase, MEDLINE, Google Scholar, and Cochrane Central Trials Register were systematically searched on 24 September 2020 for studies reporting on GBS secondary to COVID-19. Results. We identified 63 articles; we included 32 studies in our review. A total of 41 GBS cases with a confirmed or probable COVID-19 infection were reported: 26 of them were single case reports and 6 case series. Published studies on SARS-CoV-2-related GBS typically report a classic sensorimotor type of GBS often with a demyelinating electrophysiological subtype. Miller Fisher syndrome was reported in a quarter of the cases. In 78.1% of the cases, the response to immunomodulating therapy is favourable. The disease course is frequently severe and about one-third of the patients with SARS-CoV-2-associated GBS requires mechanical ventilation and Intensive Care Unit (ICU) admission. Rarely the outcome is poor or even fatal (10.8% of the cases). Conclusion. Clinical presentation, course, response to treatment, and outcome are similar in SARS-CoV-2-associated GBS and GBS due to other triggers. Full article

(This article belongs to the Special Issue Ecology, Evolution and Epidemiology of Coronaviruses)

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15 pages, 339 KiB

Open AccessEditor’s ChoiceReview

Immune Reconstitution after Haploidentical Donor and Umbilical Cord Blood Allogeneic Hematopoietic Cell Transplantation

by Hany Elmariah, Claudio G. Brunstein and Nelli Bejanyan

Life 2021, 11(2), 102; https://doi.org/10.3390/life11020102 - 29 Jan 2021

Cited by 8 | Viewed by 2712

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for a variety of hematologic diseases. However, this therapeutic platform is limited by an initial period when patients are profoundly immunocompromised. There is gradual immune recovery over time, that varies by transplant [...] Read more.

Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for a variety of hematologic diseases. However, this therapeutic platform is limited by an initial period when patients are profoundly immunocompromised. There is gradual immune recovery over time, that varies by transplant platform. Here, we review immune reconstitution after allogeneic HCT with a specific focus on two alternative donor platforms that have dramatically improved access to allogeneic HCT for patients who lack an HLA-matched related or unrelated donor: haploidentical and umbilical cord blood HCT. Despite challenges, interventions are available to mitigate the risks during the immunocompromised period including antimicrobial prophylaxis, modified immune suppression strategies, graft manipulation, and emerging adoptive cell therapies. Such interventions can improve the potential for long-term overall survival after allogeneic HCT. Full article

(This article belongs to the Special Issue Immune Reconstitution Disorders)

18 pages, 389 KiB

Open AccessEditor’s ChoiceReview

Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Blood and Cerebrospinal Fluid Biomarkers to Treatment Approaches

by Vânia Maria Sabadoto Brienze, Júlio César André, Elisabete Liso and Irina Vlasova-St. Louis

Life 2021, 11(2), 95; https://doi.org/10.3390/life11020095 - 27 Jan 2021

Cited by 9 | Viewed by 3144

Abstract

Immune reconstitution inflammatory syndrome (IRIS) presents as an exaggerated immune reaction that occurs during dysregulated immune restoration in immunocompromised patients in late-stage human immunodeficiency virus (HIV) infection who have commenced antiretroviral treatments (ART). Virtually any opportunistic pathogen can provoke this type of immune [...] Read more.

Immune reconstitution inflammatory syndrome (IRIS) presents as an exaggerated immune reaction that occurs during dysregulated immune restoration in immunocompromised patients in late-stage human immunodeficiency virus (HIV) infection who have commenced antiretroviral treatments (ART). Virtually any opportunistic pathogen can provoke this type of immune restoration disorder. In this review, we focus on recent developments in the identification of risk factors for Cryptococcal IRIS and on advancements in our understanding of C-IRIS immunopathogenesis. We overview new findings in blood and cerebrospinal fluid which can potentially be useful in the prediction and diagnosis of cryptococcal meningitis IRIS (CM-IRIS). We assess current therapeutic regimens and novel treatment approaches to combat CM-IRIS. We discuss the utility of biomarkers for clinical monitoring and adjusting treatment modalities in acquired immunodeficiency syndrome (AIDS) patients co-infected with Cryptococcus who have initiated ART. Full article

(This article belongs to the Special Issue Immune Reconstitution Disorders)

12 pages, 710 KiB

Open AccessEditor’s ChoiceReview

The Emerging Role of BDNF/TrkB Signaling in Cardiovascular Diseases

by Peng-Zhou Hang, Hua Zhu, Pei-Feng Li, Jie Liu, Feng-Qin Ge, Jing Zhao and Zhi-Min Du

Life 2021, 11(1), 70; https://doi.org/10.3390/life11010070 - 19 Jan 2021

Cited by 25 | Viewed by 3709

Abstract

Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the central nervous system. Numerous studies suggest that BDNF has extensive roles by binding to its specific receptor, tropomyosin-related kinase receptor B (TrkB), and thereby triggering downstream signaling pathways. Recently, growing [...] Read more.

Brain-derived neurotrophic factor (BDNF) is one of the most abundant neurotrophins in the central nervous system. Numerous studies suggest that BDNF has extensive roles by binding to its specific receptor, tropomyosin-related kinase receptor B (TrkB), and thereby triggering downstream signaling pathways. Recently, growing evidence highlights that the BDNF/TrkB pathway is expressed in the cardiovascular system and closely associated with the development and outcome of cardiovascular diseases (CVD), including coronary artery disease, heart failure, cardiomyopathy, hypertension, and metabolic diseases. Furthermore, circulating BDNF has also been revealed as a new potential biomarker for both diagnosis and prognosis of CVD. In this review, we discuss the current evidence of the emerging role of BDNF/TrkB signaling and address the challenges that remain in translating these discoveries to novel therapeutic strategies for CVD. Full article

(This article belongs to the Special Issue Regulating Energy Balance: Uncovering the Involvement of Neurotrophins)

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13 pages, 1362 KiB

Open AccessEditor’s ChoiceArticle

Effect of Chlorination on Microbiological Quality of Effluent of a Full-Scale Wastewater Treatment Plant

by Ioanna Zerva, Nikolaos Remmas, Ifigeneia Kagalou, Paraschos Melidis, Marina Ariantsi, Georgios Sylaios and Spyridon Ntougias

Life 2021, 11(1), 68; https://doi.org/10.3390/life11010068 - 19 Jan 2021

Cited by 15 | Viewed by 3480

Abstract

The evaluation of effluent wastewater quality mainly relies on the assessment of conventional bacterial indicators, such as fecal coliforms and enterococci; however, little is known about opportunistic pathogens, which can resist chlorination and may be transmitted in aquatic environments. In contrast to conventional [...] Read more.

The evaluation of effluent wastewater quality mainly relies on the assessment of conventional bacterial indicators, such as fecal coliforms and enterococci; however, little is known about opportunistic pathogens, which can resist chlorination and may be transmitted in aquatic environments. In contrast to conventional microbiological methods, high-throughput molecular techniques can provide an accurate evaluation of effluent quality, although a limited number of studies have been performed in this direction. In this work, high-throughput amplicon sequencing was employed to assess the effectiveness of chlorination as a disinfection method for secondary effluents. Common inhabitants of the intestinal tract, such as Bacteroides, Arcobacter and Clostridium, and activated sludge denitrifiers capable of forming biofilms, such as Acidovorax, Pseudomonas and Thauera, were identified in the chlorinated effluent. Chloroflexi with dechlorination capability and the bacteria involved in enhanced biological phosphorus removal, i.e., Candidatus Accumulibacter and Candidatus Competibacter, were also found to resist chlorination. No detection of Escherichia indicates the lack of fecal coliform contamination. Mycobacterium spp. were absent in the chlorinated effluent, whereas toxin-producing cyanobacteria of the genera Anabaena and Microcystis were identified in low abundances. Chlorination significantly affected the filamentous bacteria Nocardioides and Gordonia, whereas Zoogloea proliferated in the disinfected effluent. Moreover, perchlorate/chlorate- and organochlorine-reducing bacteria resisted chlorination. Full article

(This article belongs to the Special Issue Microbial Degradation and Biosorbents)

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17 pages, 3438 KiB

Open AccessEditor’s ChoiceReview

Cancer, Retrogenes, and Evolution

by Klaudia Staszak and Izabela Makałowska

Life 2021, 11(1), 72; https://doi.org/10.3390/life11010072 - 19 Jan 2021

Cited by 5 | Viewed by 3801

Abstract

This review summarizes the knowledge about retrogenes in the context of cancer and evolution. The retroposition, in which the processed mRNA from parental genes undergoes reverse transcription and the resulting cDNA is integrated back into the genome, results in additional copies of existing [...] Read more.

This review summarizes the knowledge about retrogenes in the context of cancer and evolution. The retroposition, in which the processed mRNA from parental genes undergoes reverse transcription and the resulting cDNA is integrated back into the genome, results in additional copies of existing genes. Despite the initial misconception, retroposition-derived copies can become functional, and due to their role in the molecular evolution of genomes, they have been named the “seeds of evolution”. It is convincing that retrogenes, as important elements involved in the evolution of species, also take part in the evolution of neoplastic tumors at the cell and species levels. The occurrence of specific “resistance mechanisms” to neoplastic transformation in some species has been noted. This phenomenon has been related to additional gene copies, including retrogenes. In addition, the role of retrogenes in the evolution of tumors has been described. Retrogene expression correlates with the occurrence of specific cancer subtypes, their stages, and their response to therapy. Phylogenetic insights into retrogenes show that most cancer-related retrocopies arose in the lineage of primates, and the number of identified cancer-related retrogenes demonstrates that these duplicates are quite important players in human carcinogenesis. Full article

(This article belongs to the Section Evolutionary Biology)

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8 pages, 1279 KiB

Open AccessEditor’s ChoiceCommunication

Dysfunction of Mitochondrial Dynamics in Drosophila Model of Diabetic Nephropathy

by Kiyoung Kim, Sun Joo Cha, Hyun-Jun Choi, Jeong Suk Kang and Eun Young Lee

Life 2021, 11(1), 67; https://doi.org/10.3390/life11010067 - 18 Jan 2021

Cited by 6 | Viewed by 3021

Abstract

Although mitochondrial dysfunction is associated with the development and progression of diabetic nephropathy (DN), its mechanisms are poorly understood, and it remains debatable whether mitochondrial morphological change is a cause of DN. In this study, a Drosophila DN model was established by treating [...] Read more.

Although mitochondrial dysfunction is associated with the development and progression of diabetic nephropathy (DN), its mechanisms are poorly understood, and it remains debatable whether mitochondrial morphological change is a cause of DN. In this study, a Drosophila DN model was established by treating a chronic high-sucrose diet that exhibits similar phenotypes in animals. Results showed that flies fed a chronic high-sucrose diet exhibited a reduction in lifespan, as well as increased lipid droplets in fat body tissue. Furthermore, the chronic high-sucrose diet effectively induced the morphological abnormalities of nephrocytes in Drosophila. High-sucrose diet induced mitochondria fusion in nephrocytes by increasing Opa1 and Marf expression. These findings establish Drosophila as a useful model for studying novel regulators and molecular mechanisms for imbalanced mitochondrial dynamics in the pathogenesis of DN. Furthermore, understanding the pathology of mitochondrial dysfunction regarding morphological changes in DN would facilitate the development of novel therapeutics. Full article

(This article belongs to the Collection Research Updates in Chronic Kidney Disease)

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14 pages, 11167 KiB

Open AccessEditor’s ChoiceArticle

Efficient Production of Chimeric Hepatitis B Virus-Like Particles Bearing an Epitope of Hepatitis E Virus Capsid by Transient Expression in Nicotiana benthamiana

by Gergana Zahmanova, Milena Mazalovska, Katerina Takova, Valentina Toneva, Ivan Minkov, Hadrien Peyret and George Lomonossoff

Life 2021, 11(1), 64; https://doi.org/10.3390/life11010064 - 17 Jan 2021

Cited by 15 | Viewed by 4050

Abstract

The core antigen of hepatitis B virus (HBcAg) is capable of self-assembly into virus-like particles (VLPs) when expressed in a number of heterologous systems. Such VLPs are potential carriers of foreign antigenic sequences for vaccine design. In this study, we evaluated the production [...] Read more.

The core antigen of hepatitis B virus (HBcAg) is capable of self-assembly into virus-like particles (VLPs) when expressed in a number of heterologous systems. Such VLPs are potential carriers of foreign antigenic sequences for vaccine design. In this study, we evaluated the production of chimeric HBcAg VLPs presenting a foreign epitope on their surface, the 551–607 amino acids (aa) immunological epitope of the ORF2 capsid protein of hepatitis E virus. A chimeric construct was made by the insertion of 56 aa into the immunodominant loop of the HBcAg. The sequences encoding the chimera were inserted into the pEAQ-HT vector and infiltrated into Nicotiana benthamiana leaves. The plant-expressed chimeric HBcHEV ORF2 551–607 protein was recognized by an anti-HBcAg mAb and anti-HEV IgG positive swine serum. Electron microscopy showed that plant-produced chimeric protein spontaneously assembled into “knobbly” ~34 nm diameter VLPs. This study shows that HBcAg is a promising carrier platform for the neutralizing epitopes of hepatitis E virus (HEV) and the chimeric HBcAg/HEV VLPs could be a candidate for a bivalent vaccine. Full article

(This article belongs to the Special Issue Capsid Protein)

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9 pages, 246 KiB

Open AccessEditor’s ChoiceArticle

Obstructive Sleep Apnea as a Risk Factor of Insulin Resistance in Nondiabetic Adults

by Monika Michalek-Zrabkowska, Piotr Macek, Helena Martynowicz, Pawel Gac, Grzegorz Mazur, Magda Grzeda and Rafal Poreba

Life 2021, 11(1), 50; https://doi.org/10.3390/life11010050 - 13 Jan 2021

Cited by 15 | Viewed by 2330

Abstract

Objective: The aim of this research was to assess the relationship between prevalence and severity of obstructive sleep apnea (OSA) and insulin resistance among patients with increased risk of OSA without diabetes mellitus. Method and materials: our study group involved 102 individuals with [...] Read more.

Objective: The aim of this research was to assess the relationship between prevalence and severity of obstructive sleep apnea (OSA) and insulin resistance among patients with increased risk of OSA without diabetes mellitus. Method and materials: our study group involved 102 individuals with suspected OSA, mean age 53.02 ± 12.37 years. Data on medical history, medication usage, sleep habits, sleep quality and daytime sleepiness, were obtained using questionnaires. All patients underwent standardized full night polysomnography. Serum fasting insulin and glucose concentration were analyzed, the homeostatic model assessment-insulin resistance (HOMA-IR) index was calculated. Results: polysomnographic study indicated that in the group with OSA mean values of apnea–hypopnea index (AHI), oxygen desaturation index (ODI), duration of SpO₂ < 90% and average desaturation drop were significantly higher compared to the group without OSA, while the minimum SpO2 was significantly lower. The carbohydrate metabolism parameters did not differ within those groups. Significantly higher fasting insulin concentration and HOMA-IR index were found in the group with AHI ≥ 15 compared to the group with AHI < 15 and in the group with AHI ≥ 30 compared to the group with AHI < 30. Higher AHI and ODI were independent risk factors for higher fasting insulin concentration and higher HOMA-IR index. Increased duration of SpO2 < 90% was an independent risk factor for higher fasting glucose concentration. Conclusions: Individuals with moderate to severe OSA without diabetes mellitus had a higher prevalence of insulin resistance. Full article

(This article belongs to the Special Issue New Radiological, Electrocardiographic and Biochemical Cardiovascular Risk Factors)

15 pages, 3009 KiB

Open AccessEditor’s ChoiceArticle

Downregulation of miR-17-92 Cluster by PERK Fine-Tunes Unfolded Protein Response Mediated Apoptosis

by Danielle E. Read, Ananya Gupta, Karen Cawley, Laura Fontana, Patrizia Agostinis, Afshin Samali and Sanjeev Gupta

Life 2021, 11(1), 30; https://doi.org/10.3390/life11010030 - 06 Jan 2021

Cited by 5 | Viewed by 2307

Abstract

An important event in the unfolded protein response (UPR) is activation of the endoplasmic reticulum (ER) kinase PERK. The PERK signalling branch initially mediates a prosurvival response, which progresses to a proapoptotic response upon prolonged ER stress. However, the molecular mechanisms of PERK-mediated [...] Read more.

An important event in the unfolded protein response (UPR) is activation of the endoplasmic reticulum (ER) kinase PERK. The PERK signalling branch initially mediates a prosurvival response, which progresses to a proapoptotic response upon prolonged ER stress. However, the molecular mechanisms of PERK-mediated cell death are not well understood. Here we show that expression of the primary miR-17-92 transcript and mature miRNAs belonging to the miR-17-92 cluster are decreased during UPR. We found that miR-17-92 promoter reporter activity was reduced during UPR in a PERK-dependent manner. Furthermore, we show that activity of the miR-17-92 promoter is repressed by ectopic expression of ATF4 and NRF2. Promoter deletion analysis mapped the region responding to UPR-mediated repression to a site in the proximal region of the miR-17-92 promoter. Hypericin-mediated photo-oxidative ER damage reduced the expression of miRNAs belonging to the miR-17-92 cluster in wild-type but not in PERK-deficient cells. Importantly, ER stress-induced apoptosis was inhibited upon miR-17-92 overexpression in SH-SY5Y and H9c2 cells. Our results reveal a novel function for ATF4 and NRF2, where repression of the miR-17-92 cluster plays an important role in ER stress-mediated apoptosis. Mechanistic details are provided for the potentiation of cell death via sustained PERK signalling mediated repression of the miR-17-92 cluster. Full article

(This article belongs to the Special Issue UPR Regulated Noncoding RNAs in Diseases)

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16 pages, 1572 KiB

Open AccessEditor’s ChoiceArticle

Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus

by Vladimir Grubelnik, Jan Zmazek, Rene Markovič, Marko Gosak and Marko Marhl

Life 2020, 10(12), 348; https://doi.org/10.3390/life10120348 - 14 Dec 2020

Cited by 16 | Viewed by 4783

Abstract

Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different [...] Read more.

Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different tissues have a central role in the pathogenesis of type 2 diabetes mellitus. In the present study, we explore how mitochondrial dysfunction impairs the coupling between metabolism and exocytosis in the pancreatic alpha and beta cells. We demonstrate that reduced mitochondrial ATP production is linked with the observed defects in insulin and glucagon secretion by utilizing computational modeling approach. Specifically, a 30–40% reduction in alpha cells’ mitochondrial function leads to a pathological shift of glucagon secretion, characterized by oversecretion at high glucose concentrations and insufficient secretion in hypoglycemia. In beta cells, the impaired mitochondrial energy metabolism is accompanied by reduced insulin secretion at all glucose levels, but the differences, compared to a normal beta cell, are the most pronounced in hyperglycemia. These findings improve our understanding of metabolic pathways and mitochondrial bioenergetics in the pathology of type 2 diabetes mellitus and might help drive the development of innovative therapies to treat various metabolic diseases. Full article

(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)

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11 pages, 2041 KiB

Open AccessEditor’s ChoiceArticle

Independent Evolution of Sex Chromosomes in Eublepharid Geckos, A Lineage with Environmental and Genotypic Sex Determination

by Eleonora Pensabene, Lukáš Kratochvíl and Michail Rovatsos

Life 2020, 10(12), 342; https://doi.org/10.3390/life10120342 - 10 Dec 2020

Cited by 16 | Viewed by 3440

Abstract

Geckos demonstrate a remarkable variability in sex determination systems, but our limited knowledge prohibits accurate conclusions on the evolution of sex determination in this group. Eyelid geckos (Eublepharidae) are of particular interest, as they encompass species with both environmental and genotypic sex determination. [...] Read more.

Geckos demonstrate a remarkable variability in sex determination systems, but our limited knowledge prohibits accurate conclusions on the evolution of sex determination in this group. Eyelid geckos (Eublepharidae) are of particular interest, as they encompass species with both environmental and genotypic sex determination. We identified for the first time the X-specific gene content in the Yucatán banded gecko, Coleonyx elegans, possessing X₁X₁X₂X₂/X₁X₂Y multiple sex chromosomes by comparative genome coverage analysis between sexes. The X-specific gene content of Coleonyx elegans was revealed to be partially homologous to genomic regions linked to the chicken autosomes 1, 6 and 11. A qPCR-based test was applied to validate a subset of X-specific genes by comparing the difference in gene copy numbers between sexes, and to explore the homology of sex chromosomes across eleven eublepharid, two phyllodactylid and one sphaerodactylid species. Homologous sex chromosomes are shared between Coleonyx elegans and Coleonyx mitratus, two species diverged approximately 34 million years ago, but not with other tested species. As far as we know, the X-specific gene content of Coleonyx elegans / Coleonyx mitratus was never involved in the sex chromosomes of other gecko lineages, indicating that the sex chromosomes in this clade of eublepharid geckos evolved independently. Full article

(This article belongs to the Section Evolutionary Biology)

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13 pages, 1725 KiB

Open AccessEditor’s ChoiceBrief Report

Sex-Specific Differences in Extracellular Vesicle Protein Cargo in Synovial Fluid of Patients with Osteoarthritis

by Ravindra Kolhe, Virgenal Owens, Ashok Sharma, Tae Jin Lee, Wenbo Zhi, Umar Ghilzai, Ashis K. Mondal, Yutao Liu, Carlos M. Isales, Mark W. Hamrick, Monte Hunter and Sadanand Fulzele

Life 2020, 10(12), 337; https://doi.org/10.3390/life10120337 - 10 Dec 2020

Cited by 22 | Viewed by 3279

Abstract

Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of [...] Read more.

Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of age-related diseases via paracrine signaling. Molecular profiling of the synovial fluid-derived EVs cargo in women may help in the discovery of novel biomarkers and therapeutics for the treatment of OA in women. Previously, we reported that synovial fluid-derived EV miRNA cargo differs in a sex-specific manner. This study aims to characterize synovial fluid-derived EV protein cargo in OA patients. Our data showed sex-specific EVs protein content in OA. We found haptoglobin, orosomucoid, and ceruloplasmin significantly up-regulated, whereas apolipoprotein down-regulated in female OA EVs. In males, we discovered β-2-glycoprotein, and complement component 5 proteins significantly up-regulated and Spt-Ada-Gcn5 acetyltransferase (SAGA)-associated factor 29 down-regulated in male OA EVs. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analysis revealed OA-specific protein involvement in several biological, molecular, and cellular pathways, specifically in inflammatory processes. In conclusion, synovial fluid EV protein content is altered in a sex-specific manner with OA, explaining the increased prevalence and severity of OA in women. Full article

(This article belongs to the Special Issue Osteoarthritis Pathology and Treatment)

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25 pages, 25235 KiB

Open AccessEditor’s ChoiceArticle

Any Role of PIK3CA and PTEN Biomarkers in the Prognosis in Oral Squamous Cell Carcinoma?

by Anna Starzyńska, Paulina Adamska, Aleksandra Sejda, Monika Sakowicz-Burkiewicz, Łukasz Jan Adamski, Giulia Marvaso, Piotr Wychowański and Barbara Alicja Jereczek-Fossa

Life 2020, 10(12), 325; https://doi.org/10.3390/life10120325 - 03 Dec 2020

Cited by 8 | Viewed by 2022

Abstract

Oral squamous cell carcinoma (OSCC) accounts for 95% of the lesions in the oral cavity. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new therapies in OSCC is urgently needed. One objective of such treatment may be a signaling [...] Read more.

Oral squamous cell carcinoma (OSCC) accounts for 95% of the lesions in the oral cavity. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new therapies in OSCC is urgently needed. One objective of such treatment may be a signaling pathway of phosphatidylinositol 3-kinase. The study group included 92 patients treated for OSCC at the University Clinical Centre in Gdańsk, Poland. Study was performed on formalin-fixed paraffin-embedded samples from primary OSCC. Phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) and phosphatase and tensin homolog encoded on chromosome 10 (PTEN) protein expression was assessed by immunohistochemistry (IHC). PIK3CA gene copy number was analyzed using chromogenic and silver in situ hybridization where molecular probes are marked by chromogens and silver ions. PIK3CA IHC H-score ≥ 70 was found in 51.65% patients, and loss of PTEN protein was noticed in 31.46% cases. PIK3CA amplification was detected in 5 tumors. In the case of PTEN protein expression, there was an inverse correlation with the T stage of the primary tumor (r = −0.243) and positive correlation with a 5-year survival (r = 0.235). The number of copies of the PIK3CA gene was associated with the tumor grading (r = 0.208). The present study shows that loss of PTEN protein and the grading (p = 0.040), distant metastases (p = 0.033), smoking (p = 0.016), and alcohol abuse (p = 0.042) were prognostic factors for the survival of patients with OSCC. In contrast, the presence of amplification and OSCC on the floor of the mouth resulted in a nearly six-fold increase in the risk of shortening survival (p = 0.037). Our finding suggests a potential prognostic significance of PTEN loss and PIK3CA amplification in OSCC. Future studies are needed to confirm our results. Full article

(This article belongs to the Special Issue Oral Cancer—Diagnosis and Therapeutics 2020)

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11 pages, 4206 KiB

Open AccessEditor’s ChoiceArticle

AFM Images of Viroid-Sized Rings That Self-Assemble from Mononucleotides through Wet–Dry Cycling: Implications for the Origin of Life

by Tue Hassenkam, Bruce Damer, Gabriel Mednick and David Deamer

Life 2020, 10(12), 321; https://doi.org/10.3390/life10120321 - 30 Nov 2020

Cited by 17 | Viewed by 2876

Abstract

It is possible that early life relied on RNA polymers that served as ribozyme-like catalysts and for storing genetic information. The source of such polymers is uncertain, but previous investigations reported that wet–dry cycles simulating prebiotic hot springs provide sufficient energy to drive [...] Read more.

It is possible that early life relied on RNA polymers that served as ribozyme-like catalysts and for storing genetic information. The source of such polymers is uncertain, but previous investigations reported that wet–dry cycles simulating prebiotic hot springs provide sufficient energy to drive condensation reactions of mononucleotides to form oligomers. The aim of the study reported here was to visualize the products by atomic force microscopy. In addition to globular oligomers, ring-like structures ranging from 10–200 nm in diameter, with an average around 30–40 nm, were abundant, particularly when nucleotides capable of base pairing were present. The thickness of the rings was consistent with single stranded products, but some had thicknesses indicating base pair stacking. Others had more complex structures in the form of short polymer attachments and pairing of rings. These observations suggest the possibility that base-pairing may promote polymerization during wet–dry cycling followed by solvation of the rings. We conclude that RNA-like rings and structures could have been synthesized non-enzymatically on the prebiotic Earth, with sizes sufficient to fold into ribozymes and genetic molecules required for life to begin. Full article

(This article belongs to the Collection Experimentally Testing Origin of Life Hypotheses in the Laboratory, at Field Analogs and Computationally)

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12 pages, 2004 KiB

Open AccessEditor’s ChoiceArticle

Numerical Investigation on the Role of Mechanical Factors Contributing to Globe Flattening in States of Elevated Intracranial Pressure

by Jafar A. Mehr, Heather E. Moss and Hamed Hatami-Marbini

Life 2020, 10(12), 316; https://doi.org/10.3390/life10120316 - 28 Nov 2020

Cited by 6 | Viewed by 3220

Abstract

Flattening of the posterior eye globe in the magnetic resonance (MR) images is a sign associated with elevated intracranial pressure (ICP), often seen in people with idiopathic intracranial hypertension (IIH). The exact underlying mechanisms of globe flattening (GF) are not fully known but [...] Read more.

Flattening of the posterior eye globe in the magnetic resonance (MR) images is a sign associated with elevated intracranial pressure (ICP), often seen in people with idiopathic intracranial hypertension (IIH). The exact underlying mechanisms of globe flattening (GF) are not fully known but mechanical factors are believed to play a role. In the present study, we investigated the effects of material properties and pressure loads on GF. For this purpose, we used a generic finite element model to investigate the deformation of the posterior eyeball. The degree of GF in numerical models and the significance of different mechanical factors on GF were characterized using an automated angle-slope technique and a statistical measure. From the numerical models, we found that ICP had the most important role in GF. We also showed that the angle-slope graphs pertaining to MR images from five people with high ICP can be represented numerically by manipulating the parameters of the finite element model. This numerical study suggests that GF observed in IIH patients can be accounted for by the forces caused by elevation of ICP from its normal level, while material properties of ocular tissues, such as sclera (SC), peripapillary sclera (PSC), and optic nerve (ON), would impact its severity. Full article

(This article belongs to the Special Issue Idiopathic Intracranial Hypertension)

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21 pages, 1274 KiB

Open AccessEditor’s ChoiceReview

Genome Editing by CRISPR-Cas: A Game Change in the Genetic Manipulation of Chlamydomonas

by Manel Ghribi, Serge Basile Nouemssi, Fatma Meddeb-Mouelhi and Isabel Desgagné-Penix

Life 2020, 10(11), 295; https://doi.org/10.3390/life10110295 - 20 Nov 2020

Cited by 29 | Viewed by 5857

Abstract

Microalgae are promising photosynthetic unicellular eukaryotes among the most abundant on the planet and are considered as alternative sustainable resources for various industrial applications. Chlamydomonas is an emerging model for microalgae to be manipulated by multiple biotechnological tools in order to produce high-value [...] Read more.

Microalgae are promising photosynthetic unicellular eukaryotes among the most abundant on the planet and are considered as alternative sustainable resources for various industrial applications. Chlamydomonas is an emerging model for microalgae to be manipulated by multiple biotechnological tools in order to produce high-value bioproducts such as biofuels, bioactive peptides, pigments, nutraceuticals, and medicines. Specifically, Chlamydomonas reinhardtii has become a subject of different genetic-editing techniques adapted to modulate the production of microalgal metabolites. The main nuclear genome-editing tools available today include zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and more recently discovered the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein (Cas) nuclease system. The latter, shown to have an interesting editing capacity, has become an essential tool for genome editing. In this review, we highlight the available literature on the methods and the applications of CRISPR-Cas for C. reinhardtii genetic engineering, including recent transformation methods, most used bioinformatic tools, best strategies for the expression of Cas protein and sgRNA, the CRISPR-Cas mediated gene knock-in/knock-out strategies, and finally the literature related to CRISPR expression and modification approaches. Full article

(This article belongs to the Special Issue Plant Synthetic Biology)

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