Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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12 pages, 885 KiB  
Article
Acute Increase in Blood αCGRP at Maximal Exercise and Its Association to Cardiorespiratory Fitness, Carbohydrate Oxidation and Work Performed: An Exploratory Study in Young Men
by Adolfo Aracil-Marco, José Manuel Sarabia, Diego Pastor, Silvia Guillén, Raúl López-Grueso, Juana Gallar and Manuel Moya-Ramón
Biology 2021, 10(8), 783; https://doi.org/10.3390/biology10080783 - 17 Aug 2021
Cited by 2 | Viewed by 2562
Abstract
This study aimed to explore if the acute variations in plasma concentration of α-calcitonin gene-related peptide (αCGRP) induced by a single maximal exercise bout may be associated to cardiorespiratory fitness and carbohydrate oxidation in humans. Twelve young adult Caucasian men (24.3 ± 0.9 [...] Read more.
This study aimed to explore if the acute variations in plasma concentration of α-calcitonin gene-related peptide (αCGRP) induced by a single maximal exercise bout may be associated to cardiorespiratory fitness and carbohydrate oxidation in humans. Twelve young adult Caucasian men (24.3 ± 0.9 years-old; 179.2 ± 1.9 cm of height; 23.9 ± 0.6 kg·m−2 body mass index) performed a graded exercise test. A venous catheter was placed before testing, and blood samples were taken at baseline, maximal effort and recovery. αCGRP was measured in plasma using a commercial double-sandwich enzyme-linked-immunoassay. A two-way repeated measurements ANOVA was used to compare the values obtained at baseline, maximal effort and recovery. In the whole sample, αCGRP increased at maximal effort and its concentration correlated directly, albeit non-significantly, with the muscle mass normalised VO2, VCO2, carbohydrate oxidation and relative power. Two thirds of the participants showed an increase in αCGRP concentration at maximal effort. Post hoc analysis showed that in these individuals, the muscle mass normalised VO2, VCO2, carbohydrate oxidation rate and relative power were higher than in the participants lacking this molecular response. Therefore, our data suggest that (a) a majority of young men respond to exercise with an increase in blood αCGRP concentration; and (b) individuals exhibiting this response also show a higher cardiorespiratory fitness, carbohydrate oxidation and work performed. These findings suggest that this neuropeptide could act as an exerkine with potential effects on physical performance. Full article
(This article belongs to the Section Physiology)
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14 pages, 2777 KiB  
Article
Bcl-xL Is Required by Primary Hippocampal Neurons during Development to Support Local Energy Metabolism at Neurites
by Joseph Jansen, Madison Scott, Emma Amjad, Allison Stumpf, Kimberly H. Lackey, Kim A. Caldwell and Han-A Park
Biology 2021, 10(8), 772; https://doi.org/10.3390/biology10080772 - 13 Aug 2021
Cited by 1 | Viewed by 2564
Abstract
B-cell lymphoma-extra large (Bcl-xL) is a mitochondrial protein known to inhibit mitochondria-dependent intrinsic apoptotic pathways. An increasing number of studies have demonstrated that Bcl-xL is critical in regulating neuronal energy metabolism and has a protective role in pathologies associated with an energy deficit. [...] Read more.
B-cell lymphoma-extra large (Bcl-xL) is a mitochondrial protein known to inhibit mitochondria-dependent intrinsic apoptotic pathways. An increasing number of studies have demonstrated that Bcl-xL is critical in regulating neuronal energy metabolism and has a protective role in pathologies associated with an energy deficit. However, it is less known how Bcl-xL regulates physiological processes of the brain. In this study, we hypothesize that Bcl-xL is required for neurite branching and maturation during neuronal development by improving local energy metabolism. We found that the absence of Bcl-xL in rat primary hippocampal neurons resulted in mitochondrial dysfunction. Specifically, the ATP/ADP ratio was significantly decreased in the neurites of Bcl-xL depleted neurons. We further found that neurons transduced with Bcl-xL shRNA or neurons treated with ABT-263, a pharmacological inhibitor of Bcl-xL, showed impaired mitochondrial motility. Neurons lacking Bcl-xL had significantly decreased anterograde and retrograde movement of mitochondria and an increased stationary mitochondrial population when Bcl-xL was depleted by either means. These mitochondrial defects, including loss of ATP, impaired normal neurite development. Neurons lacking Bcl-xL showed significantly decreased neurite arborization, growth and complexity. Bcl-xL depleted neurons also showed impaired synapse formation. These neurons showed increased intracellular calcium concentration and were more susceptible to excitotoxic challenge. Bcl-xL may support positioning of mitochondria at metabolically demanding regions of neurites like branching points. Our findings suggest a role for Bcl-xL in physiological regulation of neuronal growth and development. Full article
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16 pages, 3005 KiB  
Article
Human Blood Serum Induces p38-MAPK- and Hsp27-Dependent Migration Dynamics of Adult Human Cardiac Stem Cells: Single-Cell Analysis via a Microfluidic-Based Cultivation Platform
by Anna L. Höving, Julian Schmitz, Kazuko E. Schmidt, Johannes F. W. Greiner, Cornelius Knabbe, Barbara Kaltschmidt, Alexander Grünberger and Christian Kaltschmidt
Biology 2021, 10(8), 708; https://doi.org/10.3390/biology10080708 - 24 Jul 2021
Cited by 11 | Viewed by 2829
Abstract
Migratory capabilities of adult human stem cells are vital for assuring endogenous tissue regeneration and stem cell-based clinical applications. Although human blood serum has been shown to be beneficial for cell migration and proliferation, little is known about its impact on the migratory [...] Read more.
Migratory capabilities of adult human stem cells are vital for assuring endogenous tissue regeneration and stem cell-based clinical applications. Although human blood serum has been shown to be beneficial for cell migration and proliferation, little is known about its impact on the migratory behavior of cardiac stem cells and underlying signaling pathways. Within this study, we investigated the effects of human blood serum on primary human cardiac stem cells (hCSCs) from the adult heart auricle. On a technical level, we took advantage of a microfluidic cultivation platform, which allowed us to characterize cell morphologies and track migration of single hCSCs via live cell imaging over a period of up to 48 h. Our findings showed a significantly increased migration distance and speed of hCSCs after treatment with human serum compared to control. Exposure of blood serum-stimulated hCSCs to the p38 mitogen-activated protein kinase (p38-MAPK) inhibitor SB239063 resulted in significantly decreased migration. Moreover, we revealed increased phosphorylation of heat shock protein 27 (Hsp27) upon serum treatment, which was diminished by p38-MAPK-inhibition. In summary, we demonstrate human blood serum as a strong inducer of adult human cardiac stem cell migration dependent on p38-MAPK/Hsp27-signalling. Our findings further emphasize the great potential of microfluidic cultivation devices for assessing spatio-temporal migration dynamics of adult human stem cells on a single-cell level. Full article
(This article belongs to the Special Issue Stem Cells for Cardiovascular Biology and Medicine)
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19 pages, 3445 KiB  
Article
Genomic Selection for End-Use Quality and Processing Traits in Soft White Winter Wheat Breeding Program with Machine and Deep Learning Models
by Karansher Singh Sandhu, Meriem Aoun, Craig F. Morris and Arron H. Carter
Biology 2021, 10(7), 689; https://doi.org/10.3390/biology10070689 - 20 Jul 2021
Cited by 29 | Viewed by 5386
Abstract
Breeding for grain yield, biotic and abiotic stress resistance, and end-use quality are important goals of wheat breeding programs. Screening for end-use quality traits is usually secondary to grain yield due to high labor needs, cost of testing, and large seed requirements for [...] Read more.
Breeding for grain yield, biotic and abiotic stress resistance, and end-use quality are important goals of wheat breeding programs. Screening for end-use quality traits is usually secondary to grain yield due to high labor needs, cost of testing, and large seed requirements for phenotyping. Genomic selection provides an alternative to predict performance using genome-wide markers under forward and across location predictions, where a previous year’s dataset can be used to build the models. Due to large datasets in breeding programs, we explored the potential of the machine and deep learning models to predict fourteen end-use quality traits in a winter wheat breeding program. The population used consisted of 666 wheat genotypes screened for five years (2015–19) at two locations (Pullman and Lind, WA, USA). Nine different models, including two machine learning (random forest and support vector machine) and two deep learning models (convolutional neural network and multilayer perceptron) were explored for cross-validation, forward, and across locations predictions. The prediction accuracies for different traits varied from 0.45–0.81, 0.29–0.55, and 0.27–0.50 under cross-validation, forward, and across location predictions. In general, forward prediction accuracies kept increasing over time due to increments in training data size and was more evident for machine and deep learning models. Deep learning models were superior over the traditional ridge regression best linear unbiased prediction (RRBLUP) and Bayesian models under all prediction scenarios. The high accuracy observed for end-use quality traits in this study support predicting them in early generations, leading to the advancement of superior genotypes to more extensive grain yield trails. Furthermore, the superior performance of machine and deep learning models strengthens the idea to include them in large scale breeding programs for predicting complex traits. Full article
(This article belongs to the Special Issue Genetic Improvement and Breeding of Wheat)
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14 pages, 1326 KiB  
Article
The Role of Monk Parakeets as Nest-Site Facilitators in Their Native and Invaded Areas
by Dailos Hernández-Brito, Martina Carrete, Guillermo Blanco, Pedro Romero-Vidal, Juan Carlos Senar, Emiliano Mori, Thomas H. White, Jr., Álvaro Luna and José L. Tella
Biology 2021, 10(7), 683; https://doi.org/10.3390/biology10070683 - 19 Jul 2021
Cited by 17 | Viewed by 21814
Abstract
While most of the knowledge on invasive species focuses on their impacts, little is known about their potential positive effects on other species. Invasive ecosystem engineers can disrupt recipient environments; however, they may also facilitate access to novel resources for native species. The [...] Read more.
While most of the knowledge on invasive species focuses on their impacts, little is known about their potential positive effects on other species. Invasive ecosystem engineers can disrupt recipient environments; however, they may also facilitate access to novel resources for native species. The monk parakeet (Myiopsitta monachus) is a worldwide invader and the only parrot that builds its own communal nests, which can be used by other species. However, the ecological effects of these interspecific interactions are barely known. We compared the role of the monk parakeet as a nest-site facilitator in different rural and urban areas, both invaded and native, across three continents and eight breeding seasons. A total of 2690 nests from 42 tenant species, mostly cavity-nesting birds, were recorded in 26% of 2595 monk parakeet nests. Rural and invaded areas showed the highest abundance and richness of tenant species. Multispecies communal nests triggered interspecific aggression between the monk parakeet host and its tenants, but also a cooperative defense against predators. Despite the positive effects for native species, monk parakeets also facilitate nesting opportunities to other non-native species and may also transmit diseases to tenants, highlighting the complexity of biotic interactions in biological invasions. Full article
(This article belongs to the Section Conservation Biology and Biodiversity)
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17 pages, 2254 KiB  
Article
Suspension of Amorphous Calcium Phosphate Nanoparticles Impact Commitment of Human Adipose-Derived Stem Cells In Vitro
by Petra Wolint, Lukas Näf, Désirée Schibler, Nora Hild, Wendelin J. Stark, Pietro Giovanoli, Maurizio Calcagni and Johanna Buschmann
Biology 2021, 10(7), 675; https://doi.org/10.3390/biology10070675 - 16 Jul 2021
Cited by 2 | Viewed by 2869
Abstract
Amorphous calcium phosphate (aCaP) nanoparticles may trigger the osteogenic commitment of adipose-derived stem cells (ASCs) in vitro. The ASCs of three human donors are investigated using basal culture medium DMEM to either 5 or 50 µg/mL aCaP nanoparticles suspension (control: no nanoparticles). After [...] Read more.
Amorphous calcium phosphate (aCaP) nanoparticles may trigger the osteogenic commitment of adipose-derived stem cells (ASCs) in vitro. The ASCs of three human donors are investigated using basal culture medium DMEM to either 5 or 50 µg/mL aCaP nanoparticles suspension (control: no nanoparticles). After 7 or 14 days, stem cell marker genes, as well as endothelial, osteogenic, chondrogenic, and adipogenic genes, are analyzed by qPCR. Free calcium and phosphate ion concentrations are assessed in the cell culture supernatant. After one week and 5 µg/mL aCaP, downregulation of osteogenic markers ALP and Runx2 is found, and averaged across the three donors. Our results show that after two weeks, ALP is further downregulated, but Runx2 is upregulated. Endothelial cell marker genes, such as CD31 and CD34, are upregulated with 50 µg/mL aCaP and a 2-week exposure. Inter-donor variability is high: Two out of three donors show a significant upregulation of ALP and Runx2 at day 14 with 50 µg/mL aCaP compared to 5 µg/mL aCaP. Notably, all changes in stem cell commitment are obtained in the absence of an osteogenic medium. While the chemical composition of the culture medium and the saturation status towards calcium phosphate phases remain approximately the same for all conditions, gene expression of ASCs changes considerably. Hence, aCaP nanoparticles show the potential to trigger osteogenic and endothelial commitment in ASCs. Full article
(This article belongs to the Section Cell Biology)
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15 pages, 27351 KiB  
Article
Male Differentiation in the Marine Copepod Oithona nana Reveals the Development of a New Nervous Ganglion and Lin12-Notch-Repeat Protein-Associated Proteolysis
by Kevin Sugier, Romuald Laso-Jadart, Benoît Vacherie, Jos Käfer, Laurie Bertrand, Karine Labadie, Nathalie Martins, Céline Orvain, Emmanuelle Petit, Patrick Wincker, Jean-Louis Jamet, Adriana Alberti and Mohammed-Amin Madoui
Biology 2021, 10(7), 657; https://doi.org/10.3390/biology10070657 - 13 Jul 2021
Cited by 1 | Viewed by 2586
Abstract
Copepods are among the most numerous animals, and they play an essential role in the marine trophic web and biogeochemical cycles. The genus Oithona is described as having the highest density of copepods. The Oithona male paradox describes the activity states of males, [...] Read more.
Copepods are among the most numerous animals, and they play an essential role in the marine trophic web and biogeochemical cycles. The genus Oithona is described as having the highest density of copepods. The Oithona male paradox describes the activity states of males, which are obliged to alternate between immobile and mobile phases for ambush feeding and mate searching, respectively, while the female is less mobile and feeds less. To characterize the molecular basis of this sexual dimorphism, we combined immunofluorescence, genomics, transcriptomics, and protein–protein interaction approaches and revealed the presence of a male-specific nervous ganglion. Transcriptomic analysis showed male-specific enrichment for nervous system development-related transcripts. Twenty-seven Lin12-Notch Repeat domain-containing protein coding genes (LDPGs) of the 75 LDPGs identified in the genome were specifically expressed in males. Furthermore, some LDPGs coded for proteins with predicted proteolytic activity, and proteases-associated transcripts showed a male-specific enrichment. Using yeast double–hybrid assays, we constructed a protein–protein interaction network involving two LDPs with proteases, extracellular matrix proteins, and neurogenesis-related proteins. We also hypothesized possible roles of the LDPGs in the development of the lateral ganglia through helping in extracellular matrix lysis, neurites growth guidance, and synapses genesis. Full article
(This article belongs to the Section Developmental Biology)
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11 pages, 2052 KiB  
Article
Third Molar Agenesis Is Associated with Facial Size
by Nikolaos Gkantidis, Manuel Tacchi, Elias S. Oeschger, Demetrios Halazonetis and Georgios Kanavakis
Biology 2021, 10(7), 650; https://doi.org/10.3390/biology10070650 - 12 Jul 2021
Cited by 9 | Viewed by 4019
Abstract
Individuals with congenitally missing permanent teeth, other than third molars, present smaller craniofacial configurations compared to normal controls. However, it is not known if agenesis of third molars is part of the same mechanism. Therefore, this study assessed individuals with and without isolated [...] Read more.
Individuals with congenitally missing permanent teeth, other than third molars, present smaller craniofacial configurations compared to normal controls. However, it is not known if agenesis of third molars is part of the same mechanism. Therefore, this study assessed individuals with and without isolated third molar agenesis and tested the relation of this condition to the size of their facial configurations, using geometric morphometric methods. We show that the absence of one or more third molars is associated with a smaller maxilla, smaller mandible and a smaller overall facial configuration. The effect was larger as the number of missing third molars increased. For example, the size of the mandibular centroids in five 16-year-old females with no, one, two, three or four missing third molars showed a size reduction of approximately 2.5 mm per missing third molar. In addition, in cases with third molar agenesis in one jaw only, the effect was also evident on the opposite jaw. Our findings suggest that isolated third molar agenesis is part of a developmental mechanism resulting also in craniofacial size reduction. This might be the effect of an evolutionary process observed in humans, leading to fewer and smaller teeth, as well as smaller facial structures. Full article
(This article belongs to the Section Developmental Biology)
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14 pages, 952 KiB  
Review
GSK-3β in Pancreatic Cancer: Spotlight on 9-ING-41, Its Therapeutic Potential and Immune Modulatory Properties
by Robin Park, Andrew L. Coveler, Ludimila Cavalcante and Anwaar Saeed
Biology 2021, 10(7), 610; https://doi.org/10.3390/biology10070610 - 01 Jul 2021
Cited by 12 | Viewed by 3168
Abstract
Glycogen synthase kinase-3 beta is a ubiquitously and constitutively expressed molecule with pleiotropic function. It acts as a protooncogene in the development of several solid tumors including pancreatic cancer through its involvement in various cellular processes including cell proliferation, survival, invasion and metastasis, [...] Read more.
Glycogen synthase kinase-3 beta is a ubiquitously and constitutively expressed molecule with pleiotropic function. It acts as a protooncogene in the development of several solid tumors including pancreatic cancer through its involvement in various cellular processes including cell proliferation, survival, invasion and metastasis, as well as autophagy. Furthermore, the level of aberrant glycogen synthase kinase-3 beta expression in the nucleus is inversely correlated with tumor differentiation and survival in both in vitro and in vivo models of pancreatic cancer. Small molecule inhibitors of glycogen synthase kinase-3 beta have demonstrated therapeutic potential in pre-clinical models and are currently being evaluated in early phase clinical trials involving pancreatic cancer patients with interim results showing favorable results. Moreover, recent studies support a rationale for the combination of glycogen synthase kinase-3 beta inhibitors with chemotherapy and immunotherapy, warranting the evaluation of novel combination regimens in the future. Full article
(This article belongs to the Special Issue Role and Function of GSK-3 in the Regulation of Immunity)
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18 pages, 5823 KiB  
Article
Biocompatibility and Antibiofilm Properties of Calcium Silicate-Based Cements: An In Vitro Evaluation and Report of Two Clinical Cases
by Maurizio Bossù, Patrizia Mancini, Erika Bruni, Daniela Uccelletti, Adele Preziosi, Marco Rulli, Michela Relucenti, Orlando Donfrancesco, Flavia Iaculli, Gianni Di Giorgio, Roberto Matassa, Alessandro Salucci and Antonella Polimeni
Biology 2021, 10(6), 470; https://doi.org/10.3390/biology10060470 - 26 May 2021
Cited by 13 | Viewed by 3182
Abstract
Calcium silicate-based cements have reached excellent levels of performance in endodontics, providing predictable and successful results. To better assess the properties of these bioactive materials, the present study aimed to compare the biocompatibility and antibiofilm properties of ProRoot MTA and Biodentine. Human osteogenic [...] Read more.
Calcium silicate-based cements have reached excellent levels of performance in endodontics, providing predictable and successful results. To better assess the properties of these bioactive materials, the present study aimed to compare the biocompatibility and antibiofilm properties of ProRoot MTA and Biodentine. Human osteogenic sarcoma (Saos-2) cells were cultured on ProRoot MTA and Biodentine samples or in the presence of both cement extracts. Cell viability assay, measurement of reactive oxygen species (ROS), immunofluorescence analysis, as well as morphological evaluations were conducted. Moreover, Streptococcus mutans was used to assess the biofilm forming ability on ProRoot MTA and Biodentine disks. Finally, both cements were applied in vivo to treat immature permanent teeth affected by reversible pulpitis. Results: Cell viability assay demonstrated that Saos-2 cells had a dose- and time-dependent cytotoxicity to both analyzed cements, although cells exposed to ProRoot MTA showed a better cell vitality than those exposed to Biodentine (p < 0.001). Both cements demonstrated ROS production while this was greater in the case of Biodentine than ProRoot MTA (p < 0.001). Immunofluorescence images of the cytoskeleton and focal adhesions showed no differences in Saos-2 cells grown in the presence of ProRoot MTA eluate; whereas in the Biodentine groups, cells showed a morphology and focal adhesions more similar to that of the control sample, as the eluate concentration decreased. Morphological analysis revealed that Saos-2 cells were more flattened and exhibited better spreading when attached to ProRoot MTA disks than to Biodentine ones. The antibiofilm properties showed a time-dependent powerful inhibition of S. mutans superficial colonization and an antibiofilm effect of both cements. Clinically, complete root formation of the treated elements was achieved using the two studied cements, showing stable results over time. ProRoot MTA and Biodentine was demonstrated to be biocompatible and to possess antibiofilm properties. Their clinical application in vital pulp therapy provided successful outcomes after 2 years of follow-up. Full article
(This article belongs to the Special Issue Tissue Engineering and Regenerative Medicine)
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15 pages, 1836 KiB  
Review
Towards a Structural Mechanism for Sister Chromatid Cohesion Establishment at the Eukaryotic Replication Fork
by Sarah S. Henrikus and Alessandro Costa
Biology 2021, 10(6), 466; https://doi.org/10.3390/biology10060466 - 26 May 2021
Cited by 1 | Viewed by 3418
Abstract
Cohesion between replicated chromosomes is essential for chromatin dynamics and equal segregation of duplicated genetic material. In the G1 phase, the ring-shaped cohesin complex is loaded onto duplex DNA, enriching at replication start sites, or “origins”. During the same phase of the cell [...] Read more.
Cohesion between replicated chromosomes is essential for chromatin dynamics and equal segregation of duplicated genetic material. In the G1 phase, the ring-shaped cohesin complex is loaded onto duplex DNA, enriching at replication start sites, or “origins”. During the same phase of the cell cycle, and also at the origin sites, two MCM helicases are loaded as symmetric double hexamers around duplex DNA. During the S phase, and through the action of replication factors, cohesin switches from encircling one parental duplex DNA to topologically enclosing the two duplicated DNA filaments, which are known as sister chromatids. Despite its vital importance, the structural mechanism leading to sister chromatid cohesion establishment at the replication fork is mostly elusive. Here we review the current understanding of the molecular interactions between the replication machinery and cohesin, which support sister chromatid cohesion establishment and cohesin function. In particular, we discuss how cryo-EM is shedding light on the mechanisms of DNA replication and cohesin loading processes. We further expound how frontier cryo-EM approaches, combined with biochemistry and single-molecule fluorescence assays, can lead to understanding the molecular basis of sister chromatid cohesion establishment at the replication fork. Full article
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21 pages, 14577 KiB  
Article
Expression Analysis of FGF/FGFR and FOX Family Proteins in Mucosal Tissue Obtained from Orofacial Cleft-Affected Children
by Māra Pilmane, Nityanand Jain and Zane Vitenberga-Verza
Biology 2021, 10(5), 423; https://doi.org/10.3390/biology10050423 - 10 May 2021
Cited by 5 | Viewed by 3056
Abstract
Orofacial clefts affect hundreds of thousands of children worldwide annually and are usually corrected by a series of surgeries extending to childhood. The underlying mechanisms that lead to clefts are still unknown, mainly because of the multifactorial etiology and the myriad of interactions [...] Read more.
Orofacial clefts affect hundreds of thousands of children worldwide annually and are usually corrected by a series of surgeries extending to childhood. The underlying mechanisms that lead to clefts are still unknown, mainly because of the multifactorial etiology and the myriad of interactions between genes and environmental factors. In the present study, we investigated the role and expression of candidate genes belonging to the FGF/FGFR signaling pathway and FOX family in tissue material obtained from 12 pediatric patients undergoing cleft correction surgery. The expression was investigated using immunohistochemistry (IHC) and chromogenic in-situ hybridization (CISH) in three cell/tissue types—epithelial cells, connective tissue, and endothelial cells. We found elevated expression of FGFR1 in epithelial cells while no expression was observed in endothelial cells. Further, our results elucidate the potential pathogenetic role of FGFR1 in cellular proliferation, local site inflammation, and fibrosis in cleft patients. Along with bFGF (also called FGF2), FGFR1 could play a pro-inflammatory role in clefts. Over-amplification of FGFR2 in some patients, along with bFGF, could potentially suggest roles for these genes in angiogenesis. Additionally, increased expression of FOXE1 (also called TTF2) contributes to local site inflammation. Finally, zero to low amplification of FOXO1 could suggest its potential role in inducing oxidative stress in the endothelium along with reduced epithelial apoptosis. Full article
(This article belongs to the Section Developmental Biology)
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9 pages, 279 KiB  
Article
Hair Testing for Classic Drugs of Abuse to Monitor Cocaine Use Disorder in Patients Following Transcranial Magnetic Stimulation Protocol Treatment
by Maria Concetta Rotolo, Roberta Pacifici, Manuela Pellegrini, Stefano Cardullo, Luis J. Gómez Pérez, Diego Cuppone, Luigi Gallimberti and Graziella Madeo
Biology 2021, 10(5), 403; https://doi.org/10.3390/biology10050403 - 05 May 2021
Cited by 8 | Viewed by 3801
Abstract
In recent years, hair has become an alternative biological specimen for drug testing in the fields of forensic and clinical toxicology. The advantages of hair testing include larger detection windows (months/years), depending on the length of the hair shaft, compared to those of [...] Read more.
In recent years, hair has become an alternative biological specimen for drug testing in the fields of forensic and clinical toxicology. The advantages of hair testing include larger detection windows (months/years), depending on the length of the hair shaft, compared to those of urine/blood (hours to 2–4 days for most drugs). Segmental hair analysis can disclose a month-to-month (considering 1 cm segment cuts) information of drug exposure (single or repeated) and potentially identify patterns of drug use/administration. Repetitive transcranial magnetic stimulation (rTMS) was recently proposed as a valid tool for therapeutic purposes in addictions, including cocaine use disorder (CocUD). Here, we proposed hair testing analyses of classic drugs of abuse in a clinical setting to monitor the clinical changes in treatment-seeker CocUD patients undergoing protocol treatments with rTMS stimulating the left dorsolateral prefrontal cortex (l-DLPFC). We collected hair samples from nine CocUD patients at different stages from the beginning of treatments. Hair sample analyses revealed significant changes in the patterns of cocaine use, according to the negativity of urine screening tests and the clinical reductions of craving. These data, albeit preliminary, suggest that hair testing analysis of classic drugs of abuse could be extended to clinical settings to monitor the clinical efficacy of innovative therapeutic interventions, such as rTMS. Full article
18 pages, 3706 KiB  
Article
Drinking Molecular Hydrogen Water Is Beneficial to Cardiovascular Function in Diet-Induced Obesity Mice
by Haruchika Masuda, Atsuko Sato, Kumiko Miyata, Tomoko Shizuno, Akira Oyamada, Kazuo Ishiwata, Yoshihiro Nakagawa and Takayuki Asahara
Biology 2021, 10(5), 364; https://doi.org/10.3390/biology10050364 - 23 Apr 2021
Cited by 6 | Viewed by 4739
Abstract
Molecular hydrogen (MH) reportedly exerts therapeutic effects against inflammatory diseases as a suppressor of free radical chain reactions. Here, the cardiovascular protective effects of the intake of molecular hydrogen water (MHW) were investigated using high-fat diet-induced obesity (DIO) mice. MHW was prepared using [...] Read more.
Molecular hydrogen (MH) reportedly exerts therapeutic effects against inflammatory diseases as a suppressor of free radical chain reactions. Here, the cardiovascular protective effects of the intake of molecular hydrogen water (MHW) were investigated using high-fat diet-induced obesity (DIO) mice. MHW was prepared using supplier sticks and degassed water as control. MHW intake for 2 weeks did not improve blood sugar or body weight but decreased heart weight in DIO mice. Moreover, MHW intake improved cardiac hypertrophy, shortened the width of cardiomyocytes, dilated the capillaries and arterioles, activated myocardial eNOS-Ser-1177 phosphorylation, and restored left ventricular function in DIO mice. MHW intake promoted the histological conversion of hypertrophy to hyperplasia in white and brown adipose tissues (WAT and BAT) with the upregulation of thermogenic and cardiovascular protective genes in BAT (i.e., Ucp-1, Vegf-a, and eNos). Furthermore, the results of a colony formation assay of bone-marrow-derived endothelial progenitor cells (EPCs) indicated that MHW activated the expansion, differentiation, and mobilization of EPCs to maintain vascular homeostasis. These findings indicate that the intake of MHW exerts cardiovascular protective effects in DIO mice. Hence, drinking MHW is a potential prophylactic strategy against cardiovascular disorders in metabolic syndrome. Full article
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14 pages, 666 KiB  
Review
Extracellular Vesicles as Biomarkers and Therapeutic Tools: From Pre-Clinical to Clinical Applications
by Maria Chiara Ciferri, Rodolfo Quarto and Roberta Tasso
Biology 2021, 10(5), 359; https://doi.org/10.3390/biology10050359 - 23 Apr 2021
Cited by 74 | Viewed by 5798
Abstract
Extracellular vesicles (EVs) are ubiquitous masters of intercellular communication, being detectable in tissues, circulation, and body fluids. Their complex cargo reflects the (patho)physiologic status of the cells from which they originate. Due to these properties, the potential of EVs, and in particular exosomes, [...] Read more.
Extracellular vesicles (EVs) are ubiquitous masters of intercellular communication, being detectable in tissues, circulation, and body fluids. Their complex cargo reflects the (patho)physiologic status of the cells from which they originate. Due to these properties, the potential of EVs, and in particular exosomes, to serve as biomarkers or therapeutics has grown exponentially over the past decade. On one side, numerous studies have demonstrated that EV-associated nucleic acids and proteins are implicated in cancer progression, as well as neurodegenerative, infectious, and autoimmune disorders. On the other, the therapeutic use of EVs secreted by various cell types, and in particular stem/progenitor cells, present significant advantages in comparison to the corresponding parental cells, such as the less complex production and storage conditions. In this review, we examine some of the major pre-clinical studies dealing with EVs and exosomes, that led to the development of numerous completed clinical trials. Full article
(This article belongs to the Collection Extracellular Vesicles: From Biomarkers to Therapeutic Tools)
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27 pages, 1579 KiB  
Review
Macronutrient Determinants of Obesity, Insulin Resistance and Metabolic Health
by Jibran A. Wali, Samantha M. Solon-Biet, Therese Freire and Amanda E. Brandon
Biology 2021, 10(4), 336; https://doi.org/10.3390/biology10040336 - 16 Apr 2021
Cited by 18 | Viewed by 6615
Abstract
Obesity caused by the overconsumption of calories has increased to epidemic proportions. Insulin resistance is often associated with an increased adiposity and is a precipitating factor in the development of cardiovascular disease, type 2 diabetes, and altered metabolic health. Of the various factors [...] Read more.
Obesity caused by the overconsumption of calories has increased to epidemic proportions. Insulin resistance is often associated with an increased adiposity and is a precipitating factor in the development of cardiovascular disease, type 2 diabetes, and altered metabolic health. Of the various factors contributing to metabolic impairments, nutrition is the major modifiable factor that can be targeted to counter the rising prevalence of obesity and metabolic diseases. However, the macronutrient composition of a nutritionally balanced “healthy diet” are unclear, and so far, no tested dietary intervention has been successful in achieving long-term compliance and reductions in body weight and associated beneficial health outcomes. In the current review, we briefly describe the role of the three major macronutrients, carbohydrates, fats, and proteins, and their role in metabolic health, and provide mechanistic insights. We also discuss how an integrated multi-dimensional approach to nutritional science could help in reconciling apparently conflicting findings. Full article
(This article belongs to the Special Issue Mechanistic Insights into the Pathogenesis of Type 2 Diabetes)
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14 pages, 1425 KiB  
Article
Oxygen Dependence of Flight Performance in Ageing Drosophila melanogaster
by Valeriya Privalova, Ewa Szlachcic, Łukasz Sobczyk, Natalia Szabla and Marcin Czarnoleski
Biology 2021, 10(4), 327; https://doi.org/10.3390/biology10040327 - 14 Apr 2021
Cited by 6 | Viewed by 3100
Abstract
Similar to humans, insects lose their physical and physiological capacities with age, which makes them a convenient study system for human ageing. Although insects have an efficient oxygen-transport system, we know little about how their flight capacity changes with age and environmental oxygen [...] Read more.
Similar to humans, insects lose their physical and physiological capacities with age, which makes them a convenient study system for human ageing. Although insects have an efficient oxygen-transport system, we know little about how their flight capacity changes with age and environmental oxygen conditions. We measured two types of locomotor performance in ageing Drosophila melanogaster flies: the frequency of wing beats and the capacity to climb vertical surfaces. Flight performance was measured under normoxia and hypoxia. As anticipated, ageing flies showed systematic deterioration of climbing performance, and low oxygen impeded flight performance. Against predictions, flight performance did not deteriorate with age, and younger and older flies showed similar levels of tolerance to low oxygen during flight. We suggest that among different insect locomotory activities, flight performance deteriorates slowly with age, which is surprising, given that insect flight is one of the most energy-demanding activities in animals. Apparently, the superior capacity of insects to rapidly deliver oxygen to flight muscles remains little altered by ageing, but we showed that insects can become oxygen limited in habitats with a poor oxygen supply (e.g., those at high elevations) during highly oxygen-demanding activities such as flight. Full article
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9 pages, 752 KiB  
Article
The Evolution of Molybdenum Dependent Nitrogenase in Cyanobacteria
by Tomoaki Watanabe and Tokumasa Horiike
Biology 2021, 10(4), 329; https://doi.org/10.3390/biology10040329 - 14 Apr 2021
Cited by 10 | Viewed by 3053
Abstract
Nitrogen fixation plays a crucial role in the nitrogen cycle by helping to convert nitrogen into a form usable by other organisms. Bacteria capable of fixing nitrogen are found in six phyla including Cyanobacteria. Molybdenum dependent nitrogenase (nif) genes are thought [...] Read more.
Nitrogen fixation plays a crucial role in the nitrogen cycle by helping to convert nitrogen into a form usable by other organisms. Bacteria capable of fixing nitrogen are found in six phyla including Cyanobacteria. Molybdenum dependent nitrogenase (nif) genes are thought to share a single origin as they have homologs in various phyla. However, diazotrophic bacteria have a mosaic distribution within the cyanobacterial lineage. Therefore, the aim of this study was to determine the cause of this mosaic distribution. We identified nif gene operon structures in the genomes of 85 of the 179 cyanobacterial strains for which whole genome sequences were available. Four nif operons were conserved in each diazotroph Cyanobacterium, although there were some gene translocations and insertions. Phylogenetic inference of these genes did not reveal horizontal gene transfer from outside the phylum Cyanobacteria. These results support the hypothesis that the mosaic distribution of diazotrophic bacteria in the cyanobacterial lineage is the result of the independent loss of nif genes inherited from common cyanobacterial ancestors in each lineage. Full article
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23 pages, 3398 KiB  
Article
Effects on Steroid 5-Alpha Reductase Gene Expression of Thai Rice Bran Extracts and Molecular Dynamics Study on SRD5A2
by Chiranan Khantham, Wipawadee Yooin, Korawan Sringarm, Sarana Rose Sommano, Supat Jiranusornkul, Francisco David Carmona, Wutigri Nimlamool, Pensak Jantrawut, Pornchai Rachtanapun and Warintorn Ruksiriwanich
Biology 2021, 10(4), 319; https://doi.org/10.3390/biology10040319 - 11 Apr 2021
Cited by 23 | Viewed by 7266
Abstract
Steroid 5-alpha reductases (SRD5As) are responsible for the conversion of testosterone to dihydrotestosterone, a potent androgen, which is the aetiologic factor of androgenetic alopecia. This study aimed to compare the SRD5A gene expression suppression activity exerted by Thai rice bran extracts and their [...] Read more.
Steroid 5-alpha reductases (SRD5As) are responsible for the conversion of testosterone to dihydrotestosterone, a potent androgen, which is the aetiologic factor of androgenetic alopecia. This study aimed to compare the SRD5A gene expression suppression activity exerted by Thai rice bran extracts and their components and investigate the interactional mechanism between bioactive compounds and SRD5A2 using molecular dynamics (MD) simulation. Bran of Oryza sativa cv. Tubtim Chumphae (TRB), Yamuechaebia Morchor (YRB), Riceberry (RRB), and Malinil Surin (MRB), all rice milling by-products, was solvent-extracted. The ethanolic extract of TRB had the highest sum of overall bioactive compounds (γ-oryzanol; α-, β-, and γ-tocopherol; phenolics; and flavonoids). Among all extracts, TRB greatly downregulated the expression of SRD5A1, SRD5A2, and SRD5A3; there were no significant differences between TRB and finasteride regarding SRD5A suppression. The linear relationship and principal component analysis supported that the α-tocopherol content was correlated with the SRD5A suppression exerted by TRB. Furthermore, MD simulation demonstrated that α-tocopherol had the highest binding affinity towards SRD5A2 by interacting with residues Phe118 and Trp201. Our findings indicate that α-tocopherol effectively downregulates the expression of SRD5A genes and inhibits SRD5A2 activity, actions that are comparable to standard finasteride. TRB, a source of α-tocopherol, could be developed as an anti-hair loss product. Full article
(This article belongs to the Special Issue Bioactivity of Medicinal Plants and Extracts)
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20 pages, 3354 KiB  
Article
A Duplicated Copy of the Meiotic Gene ZIP4 Preserves up to 50% Pollen Viability and Grain Number in Polyploid Wheat
by Abdul Kader Alabdullah, Graham Moore and Azahara C. Martín
Biology 2021, 10(4), 290; https://doi.org/10.3390/biology10040290 - 02 Apr 2021
Cited by 8 | Viewed by 4819
Abstract
Although most flowering plants are polyploid, little is known of how the meiotic process evolves after polyploidisation to stabilise and preserve fertility. On wheat polyploidisation, the major meiotic gene ZIP4 on chromosome 3B duplicated onto 5B and diverged (TaZIP4-B2). TaZIP4-B2 was [...] Read more.
Although most flowering plants are polyploid, little is known of how the meiotic process evolves after polyploidisation to stabilise and preserve fertility. On wheat polyploidisation, the major meiotic gene ZIP4 on chromosome 3B duplicated onto 5B and diverged (TaZIP4-B2). TaZIP4-B2 was recently shown to promote homologous pairing, synapsis and crossover, and suppress homoeologous crossover. We therefore suspected that these meiotic stabilising effects could be important for preserving wheat fertility. A CRISPR Tazip4-B2 mutant was exploited to assess the contribution of the 5B duplicated ZIP4 copy in maintaining pollen viability and grain setting. Analysis demonstrated abnormalities in 56% of meiocytes in the Tazip4-B2 mutant, with micronuclei in 50% of tetrads, reduced size in 48% of pollen grains and a near 50% reduction in grain number. Further studies showed that most of the reduced grain number occurred when Tazip4-B2 mutant plants were pollinated with the less viable Tazip4-B2 mutant pollen rather than with wild type pollen, suggesting that the stabilising effect of TaZIP4-B2 on meiosis has a greater consequence in subsequent male, rather than female gametogenesis. These studies reveal the extraordinary value of the wheat chromosome 5B TaZIP4-B2 duplication to agriculture and human nutrition. Future studies should further investigate the role of TaZIP4-B2 on female fertility and assess whether different TaZIP4-B2 alleles exhibit variable effects on meiotic stabilisation and/or resistance to temperature change. Full article
(This article belongs to the Special Issue Crop Improvement Now and Beyond)
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20 pages, 1284 KiB  
Review
Toward the Enhancement of Microalgal Metabolite Production through Microalgae–Bacteria Consortia
by Lina Maria González-González and Luz E. de-Bashan
Biology 2021, 10(4), 282; https://doi.org/10.3390/biology10040282 - 01 Apr 2021
Cited by 44 | Viewed by 6527
Abstract
Engineered mutualistic consortia of microalgae and bacteria may be a means of assembling a novel combination of metabolic capabilities with potential biotechnological advantages. Microalgae are promising organisms for the sustainable production of metabolites of commercial interest, such as lipids, carbohydrates, pigments, and proteins. [...] Read more.
Engineered mutualistic consortia of microalgae and bacteria may be a means of assembling a novel combination of metabolic capabilities with potential biotechnological advantages. Microalgae are promising organisms for the sustainable production of metabolites of commercial interest, such as lipids, carbohydrates, pigments, and proteins. Several studies reveal that microalgae growth and cellular storage of these metabolites can be enhanced significantly by co-cultivation with growth-promoting bacteria. This review summarizes the state of the art of microalgae–bacteria consortia for the production of microalgal metabolites. We discuss the current knowledge on microalgae–bacteria mutualism and the mechanisms of bacteria to enhance microalgae metabolism. Furthermore, the potential routes for a microalgae–bacteria biorefinery are outlined in an attempt to overcome the economic failures and negative energy balances of the existing production processes. Full article
(This article belongs to the Special Issue The Path to Sustainable Production and Application of Algae)
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16 pages, 859 KiB  
Review
Microbially Mediated Chemical Ecology of Animals: A Review of Its Role in Conspecific Communication, Parasitism and Predation
by Mónica Mazorra-Alonso, Gustavo Tomás and Juan José Soler
Biology 2021, 10(4), 274; https://doi.org/10.3390/biology10040274 - 27 Mar 2021
Cited by 11 | Viewed by 4933
Abstract
Microbial symbionts are nowadays considered of pivotal importance for animal life. Among the many processes where microorganisms are involved, an emerging research avenue focuses on their major role in driving the evolution of chemical communication in their hosts. Volatiles of bacterial origin may [...] Read more.
Microbial symbionts are nowadays considered of pivotal importance for animal life. Among the many processes where microorganisms are involved, an emerging research avenue focuses on their major role in driving the evolution of chemical communication in their hosts. Volatiles of bacterial origin may underlie chemical communication and the transfer of social information through signals, as well as inadvertent social information. We reviewed the role of microorganisms in animal communication between conspecifics, and, because the microbiome may cause beneficial as well as deleterious effects on their animal hosts, we also reviewed its role in determining the outcome of the interactions with parasites and predators. Finally, we paid special attention to the hypothetical role of predation and parasitism in driving the evolution of the animal microbiome. We highlighted the novelty of the theoretical framework derived from considering the microbiota of animals in scenarios of communication, parasitism, and predation. We aimed to encourage research in these areas, suggesting key predictions that need to be tested to better understand what is one of the main roles of bacteria in animal biology. Full article
(This article belongs to the Special Issue Cues Followed by Parasites and Predators in Detecting Their Victims)
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18 pages, 3162 KiB  
Article
PER2 Circadian Oscillation Sensitizes Esophageal Cancer Cells to Chemotherapy
by Juan Alfonso Redondo, Romain Bibes, Alizée Vercauteren Drubbel, Benjamin Dassy, Xavier Bisteau, Eleonore Maury and Benjamin Beck
Biology 2021, 10(4), 266; https://doi.org/10.3390/biology10040266 - 26 Mar 2021
Cited by 9 | Viewed by 3436
Abstract
Esophageal squamous cell carcinoma (eSCC) accounts for more than 85% cases of esophageal cancer worldwide and the 5-year survival rate associated with metastatic eSCC is poor. This low survival rate is the consequence of a complex mechanism of resistance to therapy and tumor [...] Read more.
Esophageal squamous cell carcinoma (eSCC) accounts for more than 85% cases of esophageal cancer worldwide and the 5-year survival rate associated with metastatic eSCC is poor. This low survival rate is the consequence of a complex mechanism of resistance to therapy and tumor relapse. To effectively reduce the mortality rate of this disease, we need to better understand the molecular mechanisms underlying the development of resistance to therapy and translate that knowledge into novel approaches for cancer treatment. The circadian clock orchestrates several physiological processes through the establishment and synchronization of circadian rhythms. Since cancer cells need to fuel rapid proliferation and increased metabolic demands, the escape from circadian rhythm is relevant in tumorigenesis. Although clock related genes may be globally repressed in human eSCC samples, PER2 expression still oscillates in some human eSCC cell lines. However, the consequences of this circadian rhythm are still unclear. In the present study, we confirm that PER2 oscillations still occur in human cancer cells in vitro in spite of a deregulated circadian clock gene expression. Profiling of eSCC cells by RNAseq reveals that when PER2 expression is low, several transcripts related to apoptosis are upregulated. Consistently, treating eSCC cells with cisplatin when PER2 expression is low enhances DNA damage and leads to a higher apoptosis rate. Interestingly, this process is conserved in a mouse model of chemically-induced eSCC ex vivo. These results therefore suggest that response to therapy might be enhanced in esophageal cancers using chronotherapy. Full article
(This article belongs to the Special Issue Circadian Disruption and Metabolic Disorders)
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9 pages, 7962 KiB  
Article
Structural and Ultrastructural Morphological Evaluation of Giant Anteater (Myrmecophaga tridactyla) Prostate Gland
by Fernanda Moura, Letícia Sampaio, Priscila Kobayashi, Renee Laufer-Amorim, João Carlos Ferreira, Tatiane Terumi Negrão Watanabe and Carlos E. Fonseca-Alves
Biology 2021, 10(3), 231; https://doi.org/10.3390/biology10030231 - 17 Mar 2021
Cited by 5 | Viewed by 4806
Abstract
The giant anteater (Myrmecophaga tridactyla) is a vulnerable species from Central and South America, and is considered possibly extinct in Belize, Guatemala, El Salvador, and Uruguay. Due to the species’ conservation and reproductive importance, this research aimed to characterize the morphology, [...] Read more.
The giant anteater (Myrmecophaga tridactyla) is a vulnerable species from Central and South America, and is considered possibly extinct in Belize, Guatemala, El Salvador, and Uruguay. Due to the species’ conservation and reproductive importance, this research aimed to characterize the morphology, histochemical, immunohistochemical, and ultrastructural feature of the giant anteater prostate gland. For this, we collected 11 giant anteater prostate glands and performed macroscopic, morphological, histochemical, immunohistochemical, and ultrastructural analysis. Nine prostate glands from an adult subject and two from young subjects were studied. Grossly, the adult giant anteater prostate gland is divided in two distinct zones; the central zones (composed mainly of ducts) and the peripheral zones (of acini formed by secretory cells). The secretory cells showed positive periodic acid–Schiff staining. Furthermore, the immunohistochemical characterization revealed a similar human prostate pattern, with p63 staining basal cells, uroplakin III (UPIII) superficial cells of prostatic urethra, androgen receptor (AR) expressing nucleus of secretory and stromal cells, and prostatic specific antigen (PSA) staining prostatic epithelial cells. Overall, our research provided an in-depth morphological description of the giant anteater’s prostate gland, providing valuable information for futures studies focused on giant anteater conservation. Full article
(This article belongs to the Section Developmental Biology)
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78 pages, 1614 KiB  
Systematic Review
Sirtuins-Mediated System-Level Regulation of Mammalian Tissues at the Interface between Metabolism and Cell Cycle: A Systematic Review
by Parcival Maissan, Eva J. Mooij and Matteo Barberis
Biology 2021, 10(3), 194; https://doi.org/10.3390/biology10030194 - 04 Mar 2021
Cited by 21 | Viewed by 4755
Abstract
Sirtuins are a family of highly conserved NAD+-dependent proteins and this dependency links Sirtuins directly to metabolism. Sirtuins’ activity has been shown to extend the lifespan of several organisms and mainly through the post-translational modification of their many target proteins, with deacetylation being [...] Read more.
Sirtuins are a family of highly conserved NAD+-dependent proteins and this dependency links Sirtuins directly to metabolism. Sirtuins’ activity has been shown to extend the lifespan of several organisms and mainly through the post-translational modification of their many target proteins, with deacetylation being the most common modification. The seven mammalian Sirtuins, SIRT1 through SIRT7, have been implicated in regulating physiological responses to metabolism and stress by acting as nutrient sensors, linking environmental and nutrient signals to mammalian metabolic homeostasis. Furthermore, mammalian Sirtuins have been implicated in playing major roles in mammalian pathophysiological conditions such as inflammation, obesity and cancer. Mammalian Sirtuins are expressed heterogeneously among different organs and tissues, and the same holds true for their substrates. Thus, the function of mammalian Sirtuins together with their substrates is expected to vary among tissues. Any therapy depending on Sirtuins could therefore have different local as well as systemic effects. Here, an introduction to processes relevant for the actions of Sirtuins, such as metabolism and cell cycle, will be followed by reasoning on the system-level function of Sirtuins and their substrates in different mammalian tissues. Their involvement in the healthy metabolism and metabolic disorders will be reviewed and critically discussed. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
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21 pages, 1755 KiB  
Review
Emerging Roles of Metallothioneins in Beta Cell Pathophysiology: Beyond and above Metal Homeostasis and Antioxidant Response
by Mohammed Bensellam, D. Ross Laybutt and Jean-Christophe Jonas
Biology 2021, 10(3), 176; https://doi.org/10.3390/biology10030176 - 26 Feb 2021
Cited by 8 | Viewed by 3485
Abstract
Metallothioneins (MTs) are low molecular weight, cysteine-rich, metal-binding proteins whose precise biological roles have not been fully characterized. Existing evidence implicated MTs in heavy metal detoxification, metal ion homeostasis and antioxidant defense. MTs were thus categorized as protective effectors that contribute to cellular [...] Read more.
Metallothioneins (MTs) are low molecular weight, cysteine-rich, metal-binding proteins whose precise biological roles have not been fully characterized. Existing evidence implicated MTs in heavy metal detoxification, metal ion homeostasis and antioxidant defense. MTs were thus categorized as protective effectors that contribute to cellular homeostasis and survival. This view has, however, been challenged by emerging evidence in different medical fields revealing novel pathophysiological roles of MTs, including inflammatory bowel disease, neurodegenerative disorders, carcinogenesis and diabetes. In the present focused review, we discuss the evidence for the role of MTs in pancreatic beta-cell biology and insulin secretion. We highlight the pattern of specific isoforms of MT gene expression in rodents and human beta-cells. We then discuss the mechanisms involved in the regulation of MTs in islets under physiological and pathological conditions, particularly type 2 diabetes, and analyze the evidence revealing adaptive and negative roles of MTs in beta-cells and the potential mechanisms involved. Finally, we underscore the unsettled questions in the field and propose some future research directions. Full article
(This article belongs to the Special Issue Mechanistic Insights into the Pathogenesis of Type 2 Diabetes)
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18 pages, 4507 KiB  
Article
In Vivo Hepatoprotective and Nephroprotective Activity of Acylated Iridoid Glycosides from Scrophularia hepericifolia
by Maged S. Abdel-Kader and Saleh I. Alqasoumi
Biology 2021, 10(2), 145; https://doi.org/10.3390/biology10020145 - 12 Feb 2021
Cited by 7 | Viewed by 2649
Abstract
Phytochemical investigation of the chloroform fraction obtained from Scrophularia hypericifolia aerial parts led to the isolation of nine acylated iridoid glycosides. The new compounds were identified as 6-O-α-L(2″-acetyl, 3″,4″-di-O-trans-cinnamoyl) rhamnopyranosyl-6′-acetyl catalpol (6′-acetyl hypericifolin A) (1), 6-O-α-L(2″, 4″-diacetyl, 3″-O-trans [...] Read more.
Phytochemical investigation of the chloroform fraction obtained from Scrophularia hypericifolia aerial parts led to the isolation of nine acylated iridoid glycosides. The new compounds were identified as 6-O-α-L(2″-acetyl, 3″,4″-di-O-trans-cinnamoyl) rhamnopyranosyl-6′-acetyl catalpol (6′-acetyl hypericifolin A) (1), 6-O-α-L(2″, 4″-diacetyl, 3″-O-trans-cinnamoyl) rhamnopyranosyl-6′-acetyl catalpol (6′-acetyl hypericifolin B) (2), 6-O-α-L(2″-acetyl, 3″,4″-di-O-trans-cinnamoyl) rhamnopyranosyl catalpol (hypericifolin A) (3) and 6-O-α-L(2″, 4″-diacetyl, 3″-O-trans-cinnamoyl) rhamnopyranosyl catalpol (hypericifolin B) (4). Previously reported compounds were identified as laterioside (5), 8-O-acetylharpagide (6), 6-O-α-L(4′-O-trans-cinnamoyl) rhamnopyranosyl catalpol (7), lagotisoside D (8) and harpagoside (9). Identification achieved via analyses of physical and spectral data including 1D, 2D NMR and High Resolution Electrospray Ionization Mass spectroscopy (HRESIMS). Compounds 24 and 6 were subjected to biological evaluation against paracetamol-induced toxicity. The biochemical parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) as well as total bilirubin were used to access the liver condition. Measurement of serum levels of urea, creatinine, sodium and potassium cations were indicators for kidney condition. Liver and kidney samples were subjected to histopathological study. The best protection was found in the group treated with 3 followed by 4 and 6, while 2 was almost inactive. Full article
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15 pages, 2084 KiB  
Article
Entropic Competition between Supercoiled and Torsionally Relaxed Chromatin Fibers Drives Loop Extrusion through Pseudo-Topologically Bound Cohesin
by Renáta Rusková and Dušan Račko
Biology 2021, 10(2), 130; https://doi.org/10.3390/biology10020130 - 07 Feb 2021
Cited by 7 | Viewed by 59903
Abstract
We propose a model for cohesin-mediated loop extrusion, where the loop extrusion is driven entropically by the energy difference between supercoiled and torsionally relaxed chromatin fibers. Different levels of negative supercoiling are controlled by varying imposed friction between the cohesin ring and the [...] Read more.
We propose a model for cohesin-mediated loop extrusion, where the loop extrusion is driven entropically by the energy difference between supercoiled and torsionally relaxed chromatin fibers. Different levels of negative supercoiling are controlled by varying imposed friction between the cohesin ring and the chromatin fiber. The speed of generation of negative supercoiling by RNA polymerase associated with TOP1 is kept constant and corresponds to 10 rotations per second. The model was tested by coarse-grained molecular simulations for a wide range of frictions between 2 to 200 folds of that of generic fiber and the surrounding medium. The higher friction allowed for the accumulation of higher levels of supercoiling, while the resulting extrusion rate also increased. The obtained extrusion rates for the given range of investigated frictions were between 1 and 10 kbps, but also a saturation of the rate at high frictions was observed. The calculated contact maps indicate a qualitative improvement obtained at lower levels of supercoiling. The fits of mathematical equations qualitatively reproduce the loop sizes and levels of supercoiling obtained from simulations and support the proposed mechanism of entropically driven extrusion. The cohesin ring is bound on the fibers pseudo-topologically, and the model suggests that the topological binding is not necessary. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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12 pages, 1550 KiB  
Review
Systematic Review of Effectiveness of Chitosan as a Biofunctionalizer of Titanium Implants
by Nansi López-Valverde, Antonio López-Valverde and Juan Manuel Ramírez
Biology 2021, 10(2), 102; https://doi.org/10.3390/biology10020102 - 01 Feb 2021
Cited by 14 | Viewed by 2470
Abstract
Chitosan is a natural polysaccharide extracted from the shells of crustaceans that has been proposed as a scaffold in tissue engineering. Certain studies have proven a greater osseointegration of titanium surfaces that are functionalized with chitosan. The MEDLINE, CENTRAL, PubMed, and Web of [...] Read more.
Chitosan is a natural polysaccharide extracted from the shells of crustaceans that has been proposed as a scaffold in tissue engineering. Certain studies have proven a greater osseointegration of titanium surfaces that are functionalized with chitosan. The MEDLINE, CENTRAL, PubMed, and Web of Science databases were electronically searched for in vivo studies. Seven studies met the inclusion criteria. Animal models, implant site, chitosan incorporation methods, and methods of analysis were emphasized. The selected studies were individually discussed regarding the coatings, osseointegration potential, and suitability of the experimental models used, analyzing their limitations. We concluded that chitosan-biofunctionalized titanium surfaces have greater osseointegration capacity that uncoated control titanium alloys. Full article
(This article belongs to the Special Issue New Trends in Bioengineering in Osseointegration and Dental Implants)
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16 pages, 3229 KiB  
Article
Identification of an RNA Silencing Suppressor Encoded by a Symptomless Fungal Hypovirus, Cryphonectria Hypovirus 4
by Annisa Aulia, Kiwamu Hyodo, Sakae Hisano, Hideki Kondo, Bradley I. Hillman and Nobuhiro Suzuki
Biology 2021, 10(2), 100; https://doi.org/10.3390/biology10020100 - 31 Jan 2021
Cited by 17 | Viewed by 3444
Abstract
Previously, we have reported the ability of a symptomless hypovirus Cryphonectria hypovirus 4 (CHV4) of the chestnut blight fungus to facilitate stable infection by a co-infecting mycoreovirus 2 (MyRV2)—likely through the inhibitory effect of CHV4 on RNA silencing (Aulia et al., Virology, 2019). [...] Read more.
Previously, we have reported the ability of a symptomless hypovirus Cryphonectria hypovirus 4 (CHV4) of the chestnut blight fungus to facilitate stable infection by a co-infecting mycoreovirus 2 (MyRV2)—likely through the inhibitory effect of CHV4 on RNA silencing (Aulia et al., Virology, 2019). In this study, the N-terminal portion of the CHV4 polyprotein, termed p24, is identified as an autocatalytic protease capable of suppressing host antiviral RNA silencing. Using a bacterial expression system, CHV4 p24 is shown to cleave autocatalytically at the di-glycine peptide (Gly214-Gly215) of the polyprotein through its protease activity. Transgenic expression of CHV4 p24 in Cryphonectria parasitica suppresses the induction of one of the key genes of the antiviral RNA silencing, dicer-like 2, and stabilizes the infection of RNA silencing-susceptible virus MyRV2. This study shows functional similarity between CHV4 p24 and its homolog p29, encoded by the symptomatic prototype hypovirus CHV1. Full article
(This article belongs to the Special Issue Biology of Hidden Partners: Fungi and Plants)
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13 pages, 1373 KiB  
Article
Plasma Concentrations of Extracellular Vesicles Are Decreased in Patients with Post-Infarct Cardiac Remodelling
by Aleksandra Gąsecka, Kinga Pluta, Katarzyna Solarska, Bartłomiej Rydz, Ceren Eyileten, Marek Postula, Edwin van der Pol, Rienk Nieuwland, Monika Budnik, Janusz Kochanowski, Miłosz J. Jaguszewski, Łukasz Szarpak, Tomasz Mazurek, Agnieszka Kapłon-Cieślicka, Grzegorz Opolski and Krzysztof J. Filipiak
Biology 2021, 10(2), 97; https://doi.org/10.3390/biology10020097 - 30 Jan 2021
Cited by 8 | Viewed by 2654
Abstract
Background, the mechanisms underlying left ventricular remodelling (LVR) after acute myocardial infarction (AMI) remain obscure. In the course of AMI, blood cells and endothelial cells release extracellular vesicles (EVs). We hypothesized that changes in EV concentrations after AMI may underlie LVR. Methods, plasma [...] Read more.
Background, the mechanisms underlying left ventricular remodelling (LVR) after acute myocardial infarction (AMI) remain obscure. In the course of AMI, blood cells and endothelial cells release extracellular vesicles (EVs). We hypothesized that changes in EV concentrations after AMI may underlie LVR. Methods, plasma concentrations of EVs from endothelial cells (CD146+), erythrocytes (CD235a+), leukocytes (CD45+), platelets (CD61+), activated platelets (P-selectin+), and EVs exposing phosphatidylserine after AMI were determined by flow cytometry in 55 patients with the first AMI. LVR was defined as an increase in left ventricular end-diastolic volume by 20% at 6 months after AMI, compared to baseline. Results, baseline concentrations of EVs from endothelial cells, erythrocytes and platelets were lower in patients who developed LVR (p ≤ 0.02 for all). Concentrations of EVs from endothelial cells and erythrocytes were independent LVR predictors (OR 8.2, CI 1.3–54.2 and OR 17.8, CI 2.3–138.6, respectively) in multivariate analysis. Combining the three EV subtypes allowed to predict LVR with 83% sensitivity and 87% specificity. Conclusions, decreased plasma concentrations of EVs from endothelial cells, erythrocytes and platelets predict LVR after AMI. Since EV release EVs contributes to cellular homeostasis by waste removal, decreased concentrations of EVs may indicate dysfunctional cardiac homeostasis after AMI, thus promoting LVR. Full article
(This article belongs to the Collection Extracellular Vesicles: From Biomarkers to Therapeutic Tools)
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27 pages, 6857 KiB  
Article
Plant Endemism Centres and Biodiversity Hotspots in Greece
by Konstantinos Kougioumoutzis, Ioannis P. Kokkoris, Maria Panitsa, Athanasios Kallimanis, Arne Strid and Panayotis Dimopoulos
Biology 2021, 10(2), 72; https://doi.org/10.3390/biology10020072 - 20 Jan 2021
Cited by 53 | Viewed by 9015
Abstract
Biodiversity hotspots (BH) cover a small fraction of the Earth’s surface, yet host numerous endemics. Human-induced biodiversity loss has been increasing worldwide, despite attempts to halt the extinction crisis. There is thus an urgent need to efficiently allocate the available conservation funds in [...] Read more.
Biodiversity hotspots (BH) cover a small fraction of the Earth’s surface, yet host numerous endemics. Human-induced biodiversity loss has been increasing worldwide, despite attempts to halt the extinction crisis. There is thus an urgent need to efficiently allocate the available conservation funds in an optimised conservation prioritization scheme. Identifying BH and endemism centres (EC) is therefore a valuable tool in conservation prioritization and planning. Even though Greece is one of the most plant species-rich European countries, few studies have dealt with the identification of BH or EC and none has ever incorporated phylogenetic information or extended to the national scale. Consequently, we are unaware of the extent that Special Areas of Conservation (SAC) of the Natura 2000 network efficiently protect Greek plant diversity. Here, we located for the first time at a national scale and in a phylogenetic framework, the areas serving as BH and EC, and assessed the effectiveness of the Greek SAC in safeguarding them. BH and EC are mainly located near mountainous areas, and in areas supposedly floristically impoverished, such as the central Aegean islands. A critical re-assessment of the Greek SAC might be needed to minimize the extinction risk of the Greek endemics, by focusing the conservation efforts also on the BH and EC that fall outside the established Greek SAC. Full article
(This article belongs to the Section Conservation Biology and Biodiversity)
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13 pages, 1825 KiB  
Article
Human Fatalities Caused by Hornet, Wasp and Bee Stings in Spain: Epidemiology at State and Sub-State Level from 1999 to 2018
by Xesús Feás
Biology 2021, 10(2), 73; https://doi.org/10.3390/biology10020073 - 20 Jan 2021
Cited by 24 | Viewed by 10108
Abstract
Epidemiology of fatalities in Spain due to hornet, wasp, and bee stings (Cause Code of Death: X23) is described. Over a 20-year period (1999–2018), a total of 78 fatalities were recorded, mostly occurring in males (85.9%), of 65 years and older (52.6%), at [...] Read more.
Epidemiology of fatalities in Spain due to hornet, wasp, and bee stings (Cause Code of Death: X23) is described. Over a 20-year period (1999–2018), a total of 78 fatalities were recorded, mostly occurring in males (85.9%), of 65 years and older (52.6%), at “unspecified places” (67.9%), and in the months of July and August (50%). The X23 mortality rates (X23MR) expressed in terms of annual rates and per million inhabitants, varied from 0.02 to 0.19 (mean value ± standard deviation = 0.09 ± 0.05), placing Spain at low levels in comparison with other countries. A more detailed and specific breakdown of the distribution of the yearly deaths at the sub-state level and across communities reveals some striking features. They were more concentrated in the communities of Galicia (35.8%), Andalucía (21.7%), and Castilla y León (12.8%). X23MR were estimated in Galicia at 1.82, 1.10, and 2.22 in 2014, 2016, and 2018, respectively; and in Asturias at 1.88 and 0.97, in 2014 and 2017, respectively. The role of the invasive species Vespa velutina (VV) is examined. Due to its habits, abundance, and broader distribution, the risk that VV represents to human health is unmatched by other Hymenoptera native species. Full article
(This article belongs to the Section Medical Biology)
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17 pages, 725 KiB  
Article
A Modelling Framework Linking Resource-Based Stochastic Translation to the Optimal Design of Synthetic Constructs
by Peter Sarvari, Duncan Ingram and Guy-Bart Stan
Biology 2021, 10(1), 37; https://doi.org/10.3390/biology10010037 - 07 Jan 2021
Cited by 4 | Viewed by 5117
Abstract
The effect of gene expression burden on engineered cells has motivated the use of “whole-cell models” (WCMs) that use shared cellular resources to predict how unnatural gene expression affects cell growth. A common problem with many WCMs is their inability to capture translation [...] Read more.
The effect of gene expression burden on engineered cells has motivated the use of “whole-cell models” (WCMs) that use shared cellular resources to predict how unnatural gene expression affects cell growth. A common problem with many WCMs is their inability to capture translation in sufficient detail to consider the impact of ribosomal queue formation on mRNA transcripts. To address this, we have built a “stochastic cell calculator” (StoCellAtor) that combines a modified TASEP with a stochastic implementation of an existing WCM. We show how our framework can be used to link a synthetic construct’s modular design (promoter, ribosome binding site (RBS) and codon composition) to protein yield during continuous culture, with a particular focus on the effects of low-efficiency codons and their impact on ribosomal queues. Through our analysis, we recover design principles previously established in our work on burden-sensing strategies, namely that changing promoter strength is often a more efficient way to increase protein yield than RBS strength. Importantly, however, we show how these design implications can change depending on both the duration of protein expression, and on the presence of ribosomal queues. Full article
(This article belongs to the Special Issue Computational Methods in Synthetic Biology)
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19 pages, 2130 KiB  
Article
Combined Impact of No-Till and Cover Crops with or without Short-Term Water Stress as Revealed by Physicochemical and Microbiological Indicators
by Eren Taskin, Roberta Boselli, Andrea Fiorini, Chiara Misci, Federico Ardenti, Francesca Bandini, Lorenzo Guzzetti, Davide Panzeri, Nicola Tommasi, Andrea Galimberti, Massimo Labra, Vincenzo Tabaglio and Edoardo Puglisi
Biology 2021, 10(1), 23; https://doi.org/10.3390/biology10010023 - 01 Jan 2021
Cited by 5 | Viewed by 2586
Abstract
Combining no-till and cover crops (NT + CC) as an alternative to conventional tillage (CT) is generating interest to build-up farming systems’ resilience while promoting climate change adaptation in agriculture. Our field study aimed to assess the impact of long-term NT + CC [...] Read more.
Combining no-till and cover crops (NT + CC) as an alternative to conventional tillage (CT) is generating interest to build-up farming systems’ resilience while promoting climate change adaptation in agriculture. Our field study aimed to assess the impact of long-term NT + CC management and short-term water stress on soil microbial communities, enzymatic activities, and the distribution of C and N within soil aggregates. High-throughput sequencing (HTS) revealed the positive impact of NT + CC on microbial biodiversity, especially under water stress conditions, with the presence of important rhizobacteria (e.g., Bradyrhizobium spp.). An alteration index based on soil enzymes confirmed soil depletion under CT. C and N pools within aggregates showed an enrichment under NT + CC mostly due to C and N-rich large macroaggregates (LM), accounting for 44% and 33% of the total soil C and N. Within LM, C and N pools were associated to microaggregates within macroaggregates (mM), which are beneficial for long-term C and N stabilization in soils. Water stress had detrimental effects on aggregate formation and limited C and N inclusion within aggregates. The microbiological and physicochemical parameters correlation supported the hypothesis that long-term NT + CC is a promising alternative to CT, due to the contribution to soil C and N stabilization while enhancing the biodiversity and enzymes. Full article
(This article belongs to the Special Issue Linking Soil Biology to Agro-Ecosystems Functional Sustainability)
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19 pages, 3503 KiB  
Article
Inhibition of FGF and TGF-β Pathways in hESCs Identify STOX2 as a Novel SMAD2/4 Cofactor
by Peter F. Renz, Daniel Spies, Panagiota Tsikrika, Anton Wutz, Tobias A. Beyer and Constance Ciaudo
Biology 2020, 9(12), 470; https://doi.org/10.3390/biology9120470 - 16 Dec 2020
Cited by 3 | Viewed by 3893
Abstract
The fibroblast growth factor (FGF) and the transforming growth factor-β (TGF-β) pathways are both involved in the maintenance of human embryonic stem cells (hESCs) and regulate the onset of their differentiation. Their converging functions have suggested that these pathways might share a wide [...] Read more.
The fibroblast growth factor (FGF) and the transforming growth factor-β (TGF-β) pathways are both involved in the maintenance of human embryonic stem cells (hESCs) and regulate the onset of their differentiation. Their converging functions have suggested that these pathways might share a wide range of overlapping targets. Published studies have focused on the long-term effects (24–48 h) of FGF and TGF-β inhibition in hESCs, identifying direct and indirect target genes. In this study, we focused on the earliest transcriptome changes occurring between 3 and 9 h after FGF and TGF-β inhibition to identify direct target genes only. Our analysis clearly shows that only a handful of target transcripts are common to both pathways. This is surprising in light of the previous literature, and has implications for models of cell signaling in human pluripotent cells. In addition, we identified STOX2 as a novel primary target of the TGF-β signaling pathway. We show that STOX2 might act as a novel SMAD2/4 cofactor. Taken together, our results provide insights into the effect of cell signaling on the transcription profile of human pluripotent cells Full article
(This article belongs to the Special Issue Pluripotent Stem Cells, Cell Reprogramming and Tissue Modelling)
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16 pages, 4758 KiB  
Article
The Cytoplasmic LIM Domain Protein Espinas Contributes to Photoreceptor Layer Selection in the Visual System
by Alejandra Fernández-Pineda, Martí Monge-Asensio, Martín Rios and Marta Morey
Biology 2020, 9(12), 466; https://doi.org/10.3390/biology9120466 - 14 Dec 2020
Viewed by 2068
Abstract
During circuit assembly it is essential that neurons connect with their specific synaptic partners. To facilitate this process, a common strategy in many organisms is the organization of brain regions, including the fly visual system, in layers and columns. The atypical-cadherin Flamingo (Fmi) [...] Read more.
During circuit assembly it is essential that neurons connect with their specific synaptic partners. To facilitate this process, a common strategy in many organisms is the organization of brain regions, including the fly visual system, in layers and columns. The atypical-cadherin Flamingo (Fmi) and the receptor Golden Goal (Gogo) were proposed to regulate both the temporary and final layer selection of the R8 photoreceptor, through the cytoplasmic domain of Gogo. Our data suggests that Fmi intracellular signaling is also relevant for R8 final layer selection. The LIM-domain cytoplasmic molecule Espinas (Esn) binds Fmi, and they cooperatively control dendritic self-avoidance in sensory neurons. We observed defects in R8 layer selection in esn mutants with axons overshooting the final target layer, and we demonstrated that the LIM domain is necessary for layer selection. fmi knockdown in photoreceptors results in most R8 axons stalling at the temporary layer, however, we also detected R8 axons projecting past the final-target layer, and showed that fmi and esn genetically interact. Based on the previously described physical and genetic interactions between Fmi/Esn and the findings presented here, we propose that Esn signals downstream of Fmi to stabilize R8 axons in their final target layer. Full article
(This article belongs to the Section Neuroscience)
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28 pages, 569 KiB  
Review
Cutaneous Manifestations in Confirmed COVID-19 Patients: A Systematic Review
by Claudio Conforti, Caterina Dianzani, Marina Agozzino, Roberta Giuffrida, Giovanni Francesco Marangi, Nicola di Meo, Silviu-Horia Morariu, Paolo Persichetti, Francesco Segreto, Iris Zalaudek and Nicoleta Neagu
Biology 2020, 9(12), 449; https://doi.org/10.3390/biology9120449 - 05 Dec 2020
Cited by 43 | Viewed by 6992
Abstract
There have been increasing reports of skin manifestations in COVID-19 patients. We conducted a systematic review and included manuscripts describing patients with positive RT-PCR coronavirus testing from nasopharyngeal swabs who also developed cutaneous manifestations. A total of 655 patients were selected, with different [...] Read more.
There have been increasing reports of skin manifestations in COVID-19 patients. We conducted a systematic review and included manuscripts describing patients with positive RT-PCR coronavirus testing from nasopharyngeal swabs who also developed cutaneous manifestations. A total of 655 patients were selected, with different types of skin rashes: Erythematous maculopapular (n = 250), vascular (n = 146), vesicular (n = 99), urticarial (n = 98), erythema multiforme/generalized pustular figurate erythema/Stevens-Johnson syndrome (n = 22), ocular/periocular (n = 14), polymorphic pattern (n = 9), generalized pruritus (n = 8), Kawasaki disease (n = 5), atypical erythema nodosum (n = 3), and atypical Sweet syndrome (n = 1). Chilblain-like lesions were more frequent in the younger population and were linked to a milder disease course, while fixed livedo racemosa and retiform purpura appeared in older patients and seemed to predict a more severe prognosis. For vesicular rashes, PCR determined the presence of herpesviruses in the vesicle fluid, which raised the possibility of herpesvirus co-infections. The erythema-multiforme-like pattern, generalized pustular figurate erythema and Stevens-Johnson syndrome were most frequently linked to hydroxychloroquine intake. A positive PCR determination of SARS-COV-2 from conjunctival swabs suggest that eye discharge can also be contagious. These cutaneous manifestations may aid in identifying otherwise asymptomatic COVID-19 carriers in some cases or predict a more severe evolution in others. Full article
(This article belongs to the Special Issue Coronavirus Disease 2019 (COVID-19))
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19 pages, 984 KiB  
Review
Imaging of the Intestinal Microcirculation during Acute and Chronic Inflammation
by Kayle Dickson, Hajer Malitan and Christian Lehmann
Biology 2020, 9(12), 418; https://doi.org/10.3390/biology9120418 - 26 Nov 2020
Cited by 9 | Viewed by 5413
Abstract
Because of its unique microvascular anatomy, the intestine is particularly vulnerable to microcirculatory disturbances. During inflammation, pathological changes in blood flow, vessel integrity and capillary density result in impaired tissue oxygenation. In severe cases, these changes can progress to multiorgan failure and possibly [...] Read more.
Because of its unique microvascular anatomy, the intestine is particularly vulnerable to microcirculatory disturbances. During inflammation, pathological changes in blood flow, vessel integrity and capillary density result in impaired tissue oxygenation. In severe cases, these changes can progress to multiorgan failure and possibly death. Microcirculation may be evaluated in superficial tissues in patients using video microscopy devices, but these techniques do not allow the assessment of intestinal microcirculation. The gold standard for the experimental evaluation of intestinal microcirculation is intravital microscopy, a technique that allows for the in vivo examination of many pathophysiological processes including leukocyte-endothelial interactions and capillary blood flow. This review provides an overview of changes in the intestinal microcirculation in various acute and chronic inflammatory conditions. Acute conditions discussed include local infections, severe acute pancreatitis, necrotizing enterocolitis and sepsis. Inflammatory bowel disease and irritable bowel syndrome are included as examples of chronic conditions of the intestine. Full article
(This article belongs to the Special Issue Microcirculation in Health and Disease)
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23 pages, 1309 KiB  
Review
Mediators of Host–Microbe Circadian Rhythms in Immunity and Metabolism
by Katya Frazier, Mary Frith, Dylan Harris and Vanessa A. Leone
Biology 2020, 9(12), 417; https://doi.org/10.3390/biology9120417 - 25 Nov 2020
Cited by 5 | Viewed by 3142
Abstract
Circadian rhythms are essential for nearly all life forms, mediated by a core molecular gene network that drives downstream molecular processes involved in immune function and metabolic regulation. These biological rhythms serve as the body’s metronome in response to the 24-h light:dark cycle [...] Read more.
Circadian rhythms are essential for nearly all life forms, mediated by a core molecular gene network that drives downstream molecular processes involved in immune function and metabolic regulation. These biological rhythms serve as the body’s metronome in response to the 24-h light:dark cycle and other timed stimuli. Disrupted circadian rhythms due to drastic lifestyle and environmental shifts appear to contribute to the pathogenesis of metabolic diseases, although the mechanisms remain elusive. Gut microbiota membership and function are also key mediators of metabolism and are highly sensitive to environmental perturbations. Recent evidence suggests rhythmicity of gut microbes is essential for host metabolic health. The key molecular mediators that transmit rhythmic signals between microbes and host metabolic networks remain unclear, but studies suggest the host immune system may serve as a conduit between these two systems, providing homeostatic signals to maintain overall metabolic health. Despite this knowledge, the precise mechanism and communication modalities that drive these rhythms remain unclear, especially in humans. Here, we review the current literature examining circadian dynamics of gut microbes, the immune system, and metabolism in the context of metabolic dysregulation and provide insights into gaps and challenges that remain. Full article
(This article belongs to the Special Issue Circadian Disruption and Metabolic Disorders)
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21 pages, 1656 KiB  
Review
Microbiota and Obesity: Where Are We Now?
by Andrea Ballini, Salvatore Scacco, Mariarosaria Boccellino, Luigi Santacroce and Roberto Arrigoni
Biology 2020, 9(12), 415; https://doi.org/10.3390/biology9120415 - 25 Nov 2020
Cited by 50 | Viewed by 5878
Abstract
Genetic and environmental factors are underlying causes of obesity and other metabolic diseases, so it is therefore difficult to find suitable and effective medical treatments. However, without a doubt, the gut microbiota—and also the bacteria present in the oral cavity—act as key factors [...] Read more.
Genetic and environmental factors are underlying causes of obesity and other metabolic diseases, so it is therefore difficult to find suitable and effective medical treatments. However, without a doubt, the gut microbiota—and also the bacteria present in the oral cavity—act as key factors in the development of these pathologies, yet the mechanisms have not been fully described. Certainly, a more detailed knowledge of the structure of the microbiota—composition, intra- and inter-species relationships, metabolic functions—could be of great help in counteracting the onset of obesity. Identifying key bacterial species will allow us to create a database of “healthy” bacteria, making it possible to manipulate the bacterial community according to metabolic and clinical needs. Targeting gut microbiota in clinical care as treatment for obesity and health-related complications—even just for weight loss has become a real possibility. In this topical review we provide an overview of the role of the microbiota on host energy homeostasis and obesity-related metabolic diseases, therefore addressing the therapeutic potential of novel and existing strategies (impact of nutrition/dietary modulation, and fecal microbiota transplantation) in the treatment of metabolic disease. Full article
(This article belongs to the Special Issue New Trends in Precision Medicine, Dentistry and Oral Health)
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17 pages, 971 KiB  
Review
Metabolic Cancer-Macrophage Crosstalk in the Tumor Microenvironment
by Kyra E. de Goede, Amber J. M. Driessen and Jan Van den Bossche
Biology 2020, 9(11), 380; https://doi.org/10.3390/biology9110380 - 07 Nov 2020
Cited by 26 | Viewed by 5168
Abstract
Tumors consist of a wide variety of cells, including immune cells, that affect tumor progression. Macrophages are abundant innate immune cells in the tumor microenvironment (TME) and are crucial in regulating tumorigenicity. Specific metabolic conditions in the TME can alter the phenotype of [...] Read more.
Tumors consist of a wide variety of cells, including immune cells, that affect tumor progression. Macrophages are abundant innate immune cells in the tumor microenvironment (TME) and are crucial in regulating tumorigenicity. Specific metabolic conditions in the TME can alter the phenotype of tumor-associated macrophages (TAMs) in a direction that supports their pro-tumor functions. One of these conditions is the accumulation of metabolites, also known as oncometabolites. Interactions of oncometabolites with TAMs can promote a pro-tumorigenic phenotype, thereby sustaining cancer cell growth and decreasing the chance of eradication. This review focuses on the metabolic cancer-macrophage crosstalk in the TME. We discuss how cancer cell metabolism and oncometabolites affect macrophage phenotype and function, and conversely how macrophage metabolism can impact tumor progression. Lastly, we propose tumor-secreted exosome-mediated metabolic signaling as a potential factor in tumorigenesis. Insight in these processes may contribute to the development of novel cancer therapies. Full article
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12 pages, 2230 KiB  
Article
Kin-Mediated Male Choice and Alternative Reproductive Tactics in Spider Mites
by Peter Schausberger and Yukie Sato
Biology 2020, 9(11), 360; https://doi.org/10.3390/biology9110360 - 26 Oct 2020
Cited by 5 | Viewed by 2557
Abstract
Optimal outbreeding and kin selection theories state that the degree of kinship is a fundamental determinant in any mating system. However, the role of kinship in male choice and alternative reproductive tactics (ARTs) is poorly known. We assessed the influence of kinship on [...] Read more.
Optimal outbreeding and kin selection theories state that the degree of kinship is a fundamental determinant in any mating system. However, the role of kinship in male choice and alternative reproductive tactics (ARTs) is poorly known. We assessed the influence of kinship on male choice and expression of ARTs in two populations of two-spotted spider mites Tetranychus urticae. Male spider mites guard premature females, which is an indicator of mate choice, and may conditionally adopt fighting or sneaking tactics to secure access to females. Males competing with kin or non-kin were offered one kin or non-kin female (experiment 1) and single males were presented a choice of kin and non-kin females (experiment 2). Under kin competition, males of both populations were more prone to guard non-kin than kin females at a 3:1 fighter:sneaker ratio. Under non-kin competition, all males were fighters. Under no-choice, males used novelty as indicator of genetic dissimilarity, serving as absolute decision rule for outbreeding. Under choice, comparative evaluation allowed males to preferentially guard females with higher reproductive potential. Overall, our study suggests that male spider mites can assess kinship of rivals and prospective mates. Kin discrimination allows adaptive, context-specific non-random mating preference and adjustment of ARTs. Full article
(This article belongs to the Section Behavioural Biology)
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15 pages, 2316 KiB  
Article
Cloning of Thalassiosira pseudonana’s Mitochondrial Genome in Saccharomyces cerevisiae and Escherichia coli
by Ryan R. Cochrane, Stephanie L. Brumwell, Arina Shrestha, Daniel J. Giguere, Samir Hamadache, Gregory B. Gloor, David R. Edgell and Bogumil J. Karas
Biology 2020, 9(11), 358; https://doi.org/10.3390/biology9110358 - 26 Oct 2020
Cited by 3 | Viewed by 3928
Abstract
Algae are attractive organisms for biotechnology applications such as the production of biofuels, medicines, and other high-value compounds due to their genetic diversity, varied physical characteristics, and metabolic processes. As new species are being domesticated, rapid nuclear and organelle genome engineering methods need [...] Read more.
Algae are attractive organisms for biotechnology applications such as the production of biofuels, medicines, and other high-value compounds due to their genetic diversity, varied physical characteristics, and metabolic processes. As new species are being domesticated, rapid nuclear and organelle genome engineering methods need to be developed or optimized. To that end, we have previously demonstrated that the mitochondrial genome of microalgae Phaeodactylum tricornutum can be cloned and engineered in Saccharomyces cerevisiae and Escherichia coli. Here, we show that the same approach can be used to clone mitochondrial genomes of another microalga, Thalassiosira pseudonana. We have demonstrated that these genomes can be cloned in S. cerevisiae as easily as those of P. tricornutum, but they are less stable when propagated in E. coli. Specifically, after approximately 60 generations of propagation in E. coli, 17% of cloned T. pseudonana mitochondrial genomes contained deletions compared to 0% of previously cloned P. tricornutum mitochondrial genomes. This genome instability is potentially due to the lower G+C DNA content of T. pseudonana (30%) compared to P. tricornutum (35%). Consequently, the previously established method can be applied to clone T. pseudonana’s mitochondrial genome, however, more frequent analyses of genome integrity will be required following propagation in E. coli prior to use in downstream applications. Full article
(This article belongs to the Special Issue Exploring and Designing Novel Microbes for Biotechnology)
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10 pages, 1593 KiB  
Article
The Effect of a 13-Valent Conjugate Pneumococcal Vaccine on Circulating Antibodies Against Oxidized LDL and Phosphorylcholine in Man, A Randomized Placebo-Controlled Clinical Trial
by Hendrika W. Grievink, Pim Gal, Maria Ozsvar Kozma, Erica S. Klaassen, Johan Kuiper, Jacobus Burggraaf, Christoph J. Binder and Matthijs Moerland
Biology 2020, 9(11), 345; https://doi.org/10.3390/biology9110345 - 22 Oct 2020
Cited by 7 | Viewed by 2373
Abstract
In mice vaccination with Streptococcus pneumoniae results in an increase in anti-oxLDL IgM antibodies due to mimicry of anti-phosphorylcholine (present in the cell wall of S. pneumoniae) and anti-oxLDL IgM. In this study we investigated the human translation of this molecular mimicry [...] Read more.
In mice vaccination with Streptococcus pneumoniae results in an increase in anti-oxLDL IgM antibodies due to mimicry of anti-phosphorylcholine (present in the cell wall of S. pneumoniae) and anti-oxLDL IgM. In this study we investigated the human translation of this molecular mimicry by vaccination against S. pneumoniae using the Prevenar-13 vaccine. Twenty-four healthy male volunteers were vaccinated with Prevenar-13, either three times, twice or once in a double-blind, placebo-controlled, randomized single center clinical study. Anti-pneumococcal wall, oxLDL and phosphorycholine antibody levels were measured at a fixed serum dilution, as well as circulating lipid levels over the course of 68 weeks. A significant increase in anti-oxLDL IgG and IgM was seen in the group receiving two doses six months apart compared to the placebo. However, these differences were not observed in the groups receiving a single dose, two doses one month apart, or three doses. This study shows that vaccination with Prevenar-13 does not result in robust anti-oxLDL IgM levels in humans. Further research would be required to test alternative pneumococcal-based vaccines, vaccination regimens or study populations, such as cardiovascular disease patients. Full article
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16 pages, 2531 KiB  
Article
Super-Resolution Fluorescence Microscopy Reveals Clustering Behaviour of Chlamydia pneumoniae’s Major Outer Membrane Protein
by Amy E. Danson, Alex McStea, Lin Wang, Alice Y. Pollitt, Marisa L. Martin-Fernandez, Isabel Moraes, Martin A. Walsh, Sheila MacIntyre and Kimberly A. Watson
Biology 2020, 9(10), 344; https://doi.org/10.3390/biology9100344 - 20 Oct 2020
Cited by 5 | Viewed by 4251
Abstract
Chlamydia pneumoniae is a Gram-negative bacterium responsible for a number of human respiratory diseases and linked to some chronic inflammatory diseases. The major outer membrane protein (MOMP) of Chlamydia is a conserved immunologically dominant protein located in the outer membrane, which, together with [...] Read more.
Chlamydia pneumoniae is a Gram-negative bacterium responsible for a number of human respiratory diseases and linked to some chronic inflammatory diseases. The major outer membrane protein (MOMP) of Chlamydia is a conserved immunologically dominant protein located in the outer membrane, which, together with its surface exposure and abundance, has led to MOMP being the main focus for vaccine and antimicrobial studies in recent decades. MOMP has a major role in the chlamydial outer membrane complex through the formation of intermolecular disulphide bonds, although the exact interactions formed are currently unknown. Here, it is proposed that due to the large number of cysteines available for disulphide bonding, interactions occur between cysteine-rich pockets as opposed to individual residues. Such pockets were identified using a MOMP homology model with a supporting low-resolution (~4 Å) crystal structure. The localisation of MOMP in the E. coli membrane was assessed using direct stochastic optical reconstruction microscopy (dSTORM), which showed a decrease in membrane clustering with cysteine-rich regions containing two mutations. These results indicate that disulphide bond formation was not disrupted by single mutants located in the cysteine-dense regions and was instead compensated by neighbouring cysteines within the pocket in support of this cysteine-rich pocket hypothesis. Full article
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16 pages, 3537 KiB  
Article
Coupling of the AQUATOX and EFDC Models for Ecological Impact Assessment of Chemical Spill Scenarios in the Jeonju River, Korea
by Jaehoon Yeom, Injeong Kim, Minjeong Kim, Kyunghwa Cho and Sang Don Kim
Biology 2020, 9(10), 340; https://doi.org/10.3390/biology9100340 - 19 Oct 2020
Cited by 2 | Viewed by 3207
Abstract
In this study, an ecological impact was assessed for the short-term leak scenario through the AQUATOX-EFDC model, which combines the proven ecological model AQUATOX with the hydrodynamic model EFDC. A case study of the coupled AQUATOX-EFDC model was conducted for 30–30,000 kg toluene [...] Read more.
In this study, an ecological impact was assessed for the short-term leak scenario through the AQUATOX-EFDC model, which combines the proven ecological model AQUATOX with the hydrodynamic model EFDC. A case study of the coupled AQUATOX-EFDC model was conducted for 30–30,000 kg toluene leak scenarios in the Jeonju River in South Korea. A 21-day scenario simulation was conducted, and the impact of the toluene spill accident was evaluated by comparing the biomass between the control simulation and the perturbed simulation. As a result of the simulation, it was found that in the scenario in which 3000 kg of toluene was leaked for a day, a substantial change was expected in the range of 0–640 m from the accident site. Additionally, for a 30,000 kg leak, a substantial change was expected in the range of 0–2300 m from the accident site, and the greatest damage was observed for the fish species group, the top predators. As a result, the AQUATOX-EFDC simulation showed a significant ecological impact, and the proposed model will be helpful to understand the ecological impact and establish the management strategy for the ecological risk of the chemical spill. Full article
(This article belongs to the Section Ecology)
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14 pages, 2420 KiB  
Review
Recommendations, Practices and Infrastructural Model for the Dental Radiology Set-up in Clinical and Academic Institutions in the COVID-19 Era
by Anu Sushanth. A, Kumar Chandan Srivastava, Deepti Shrivastava, Hala A. Hosni, Zafar Ali Khan, Khalid Al-Johani, Ibrahim A Alzoubi, Sasirekha B, Mohammed Ghazi Sghaireen and Mohammad Khursheed Alam
Biology 2020, 9(10), 334; https://doi.org/10.3390/biology9100334 - 13 Oct 2020
Cited by 10 | Viewed by 4577
Abstract
The pandemic of Coronavirus disease (COVID-19) has emerged as a global catastrophe that is plaguing mankind. In the past eight months since the world discovered about COVID-19, we learned a lot about server acute respiratory syndrome coronavirus 2 (SARS CoV-2) and perhaps there [...] Read more.
The pandemic of Coronavirus disease (COVID-19) has emerged as a global catastrophe that is plaguing mankind. In the past eight months since the world discovered about COVID-19, we learned a lot about server acute respiratory syndrome coronavirus 2 (SARS CoV-2) and perhaps there is much more to discover and understand about the virus. With the current understanding of the disease, we assume it will remain in an active state of transmission and progression among the community for a long time. Thus, it is advisable to adopt the disease’s prevention protocol in our daily and work routine. During this pandemic patient requiring dental treatment cannot be neglected and the role of dental imaging is crucial in delivering treatment. Hence, this article attempts to provide an evidence-based compilation about the mode of transmission and clinical features of COVID-19. It also throws light on the potential source of disease transmission in the dental radiology setting. In addition, it suggests preventive measures to curb the infection and infrastructural model of the clinical setting that will assist in achieving control over the disease transmission. This article intends to project a strategy about protocols, infrastructure, and daily activities in a dental radiology office that institutions can adopt with modifications according to their local scenario. Full article
(This article belongs to the Special Issue Coronavirus Disease 2019 (COVID-19))
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14 pages, 3420 KiB  
Article
Clinical Veterinary Boron Neutron Capture Therapy (BNCT) Studies in Dogs with Head and Neck Cancer: Bridging the Gap between Translational and Clinical Studies
by Amanda E. Schwint, Andrea Monti Hughes, Marcela A. Garabalino, Gustavo A. Santa Cruz, Sara J. González, Juan Longhino, Lucas Provenzano, Paulina Oña, Monica Rao, María de los Ángeles Cantarelli, Andrea Leiras, María Silvina Olivera, Verónica A. Trivillin, Paula Alessandrini, Fabricio Brollo, Esteban Boggio, Hernan Costa, Romina Ventimiglia, Sergio Binia, Emiliano C. C. Pozzi, Susana I. Nievas and Iara S. Santa Cruzadd Show full author list remove Hide full author list
Biology 2020, 9(10), 327; https://doi.org/10.3390/biology9100327 - 07 Oct 2020
Cited by 16 | Viewed by 3696
Abstract
Translational Boron Neutron Capture Therapy (BNCT) studies performed by our group and clinical BNCT studies worldwide have shown the therapeutic efficacy of BNCT for head and neck cancer. The present BNCT studies in veterinary patients with head and neck cancer were performed to [...] Read more.
Translational Boron Neutron Capture Therapy (BNCT) studies performed by our group and clinical BNCT studies worldwide have shown the therapeutic efficacy of BNCT for head and neck cancer. The present BNCT studies in veterinary patients with head and neck cancer were performed to optimize the therapeutic efficacy of BNCT, contribute towards exploring the role of BNCT in veterinary medicine, put in place technical aspects for an upcoming clinical trial of BNCT for head and neck cancer at the RA-6 Nuclear Reactor, and assess the feasibility of employing the existing B2 beam to treat large, deep-seated tumors. Five dogs with head and neck cancer with no other therapeutic option were treated with two applications of BNCT mediated by boronophenyl-alanine (BPA) separated by 3–5 weeks. Two to three portals per BNCT application were used to achieve a potentially therapeutic dose over the tumor without exceeding normal tissue tolerance. Clinical and Computed Tomography results evidenced partial tumor control in all cases, with slight-moderate mucositis, excellent life quality, and prolongation in the survival time estimated at recruitment. These exploratory studies show the potential value of BNCT in veterinary medicine and contribute towards initiating a clinical BNCT trial for head and neck cancer at the RA-6 clinical facility. Full article
(This article belongs to the Special Issue Boron Neutron Capture Therapy: From Nuclear Physics to Biomedicine)
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24 pages, 4313 KiB  
Article
Exogenous Abscisic Acid Can Influence Photosynthetic Processes in Peas through a Decrease in Activity of H+-ATP-ase in the Plasma Membrane
by Lyubov Yudina, Ekaterina Sukhova, Oksana Sherstneva, Marina Grinberg, Maria Ladeynova, Vladimir Vodeneev and Vladimir Sukhov
Biology 2020, 9(10), 324; https://doi.org/10.3390/biology9100324 - 04 Oct 2020
Cited by 19 | Viewed by 2804
Abstract
Abscisic acid (ABA) is an important hormone in plants that participates in their acclimation to the action of stressors. Treatment by exogenous ABA and its synthetic analogs are a potential way of controlling the tolerance of agricultural plants; however, the mechanisms of influence [...] Read more.
Abscisic acid (ABA) is an important hormone in plants that participates in their acclimation to the action of stressors. Treatment by exogenous ABA and its synthetic analogs are a potential way of controlling the tolerance of agricultural plants; however, the mechanisms of influence of the ABA treatment on photosynthetic processes require further investigations. The aim of our work was to investigate the participation of inactivation of the plasma membrane H+-ATP-ase on the influence of ABA treatment on photosynthetic processes and their regulation by electrical signals in peas. The ABA treatment of seedlings was performed by spraying them with aqueous solutions (10−5 M). The combination of a Dual-PAM-100 PAM fluorometer and GFS-3000 infrared gas analyzer was used for photosynthetic measurements; the patch clamp system on the basis of a SliceScope Pro 2000 microscope was used for measurements of electrical activity. It was shown that the ABA treatment stimulated the cyclic electron flow around photosystem I and decreased the photosynthetic CO2 assimilation, the amplitude of burning-induced electrical signals (variation potentials), and the magnitude of photosynthetic responses relating to these signals; in contrast, treatment with exogenous ABA increased the heat tolerance of photosynthesis. An investigation of the influence of ABA treatment on the metabolic component of the resting potential showed that this treatment decreased the activity of the H+-ATP-ase in the plasma membrane. Inhibitor analysis using sodium orthovanadate demonstrated that this decrease may be a mechanism of the ABA treatment-induced changes in photosynthetic processes, their heat tolerance, and regulation by electrical signals. Full article
(This article belongs to the Section Plant Science)
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