Biology

Open AccessArticle

Virtual and In Vitro Screening of Natural Products Identifies Indole and Benzene Derivatives as Inhibitors of SARS-CoV-2 Main Protease (M^pro)

by

Dony Ang

,

Riley Kendall

and

Hagop S. Atamian

Biology 2023, 12(4), 519; https://doi.org/10.3390/biology12040519 (registering DOI) - 29 Mar 2023

Abstract

The rapid spread of the coronavirus disease 2019 (COVID-19) resulted in serious health, social, and economic consequences. While the development of effective vaccines substantially reduced the severity of symptoms and the associated deaths, we still urgently need effective drugs to further reduce the [...] Read more.

The rapid spread of the coronavirus disease 2019 (COVID-19) resulted in serious health, social, and economic consequences. While the development of effective vaccines substantially reduced the severity of symptoms and the associated deaths, we still urgently need effective drugs to further reduce the number of casualties associated with SARS-CoV-2 infections. Machine learning methods both improved and sped up all the different stages of the drug discovery processes by performing complex analyses with enormous datasets. Natural products (NPs) have been used for treating diseases and infections for thousands of years and represent a valuable resource for drug discovery when combined with the current computation advancements. Here, a dataset of 406,747 unique NPs was screened against the SARS-CoV-2 main protease (M^pro) crystal structure (6lu7) using a combination of ligand- and structural-based virtual screening. Based on 1) the predicted binding affinities of the NPs to the M^pro, 2) the types and number of interactions with the M^pro amino acids that are critical for its function, and 3) the desirable pharmacokinetic properties of the NPs, we identified the top 20 candidates that could potentially inhibit the M^pro protease function. A total of 7 of the 20 top candidates were subjected to in vitro protease inhibition assay and 4 of them (4/7; 57%), including two beta carbolines, one N-alkyl indole, and one Benzoic acid ester, had significant inhibitory activity against M^pro protease. These four NPs could be developed further for the treatment of COVID-19 symptoms. Full article

(This article belongs to the Section Pharmacology)

► Show Figures

Figure 1

Open AccessArticle

Inferring Gene Regulatory Networks from RNA-seq Data Using Kernel Classification

by

,

,

,

and

Biology 2023, 12(4), 518; https://doi.org/10.3390/biology12040518 (registering DOI) - 29 Mar 2023

Abstract

Gene expression profiling is one of the most recognized techniques for inferring gene regulators and their potential targets in gene regulatory networks (GRN). The purpose of this study is to build a regulatory network for the budding yeast Saccharomyces cerevisiae genome by incorporating [...] Read more.

Gene expression profiling is one of the most recognized techniques for inferring gene regulators and their potential targets in gene regulatory networks (GRN). The purpose of this study is to build a regulatory network for the budding yeast Saccharomyces cerevisiae genome by incorporating the use of RNA-seq and microarray data represented by a wide range of experimental conditions. We introduce a pipeline for data analysis, data preparation, and training models. Several kernel classification models; including one-class, two-class, and rare event classification methods, are used to categorize genes. We test the impact of the normalization techniques on the overall performance of RNA-seq. Our findings provide new insights into the interactions between genes in the yeast regulatory network. The conclusions of our study have significant importance since they highlight the effectiveness of classification and its contribution towards enhancing the present comprehension of the yeast regulatory network. When assessed, our pipeline demonstrates strong performance across different statistical metrics, such as a 99% recall rate and a 98% AUC score. Full article

(This article belongs to the Special Issue Multi-Omics Co-expression Network Analysis)

Open AccessCommunication

Overexpression of the Brassica rapa bZIP Transcription Factor, BrbZIP-S, Increases the Stress Tolerance in Nicotiana benthamiana

by

Seung Hee Eom

,

Heung Bin Lim

and

Tae Kyung Hyun

Biology 2023, 12(4), 517; https://doi.org/10.3390/biology12040517 (registering DOI) - 29 Mar 2023

Abstract

In higher plants, S₁-basic region-leucine zipper (S₁-bZIP) transcription factors fulfill crucial roles in the physiological homeostasis of carbon and amino acid metabolisms and stress responses. However, very little is known about the physiological role of S₁-bZIP in [...] Read more.

In higher plants, S₁-basic region-leucine zipper (S₁-bZIP) transcription factors fulfill crucial roles in the physiological homeostasis of carbon and amino acid metabolisms and stress responses. However, very little is known about the physiological role of S₁-bZIP in cruciferous vegetables. Here, we analyzed the physiological function of S₁-bZIP from Brassica rapa (BrbZIP-S) in modulating proline and sugar metabolism. Overexpression of BrbZIP-S in Nicotiana benthamiana resulted in delayed chlorophyll degradation during the response to dark conditions. Under heat stress or recovery conditions, the transgenic lines exhibited a lower accumulation of H₂O₂, malondialdehyde, and protein carbonyls compared to the levels in transgenic control plants. These results strongly indicate that BrbZIP-S regulates plant tolerance against dark and heat stress. We propose that BrbZIP-S is a modulator of proline and sugar metabolism, which are required for energy homeostasis in response to environmental stress conditions. Full article

(This article belongs to the Special Issue Abiotic Stress in Plants and Resilience: Recent Advances)

► Show Figures

Figure 1

Open AccessArticle

Comparative Study of Lingual Papillae, Lingual Glands and Lyssa of the Tongue of Selected Wild Felids (Carnivora, Felidae) in Biological Aspects

by

Karolina Goździewska-Harłajczuk

,

Karolina Barszcz

,

Joanna Klećkowska-Nawrot

,

,

,

and

Biology 2023, 12(4), 516; https://doi.org/10.3390/biology12040516 (registering DOI) - 29 Mar 2023

Abstract

Although much attention has been paid in the literature to the morphology of the tongue in various animal species, including some Felidae, it has not yet been described in detail in the vulnerable Neofelis nebulosa and Panthera leo bleyenberghi and the last concern [...] Read more.

Although much attention has been paid in the literature to the morphology of the tongue in various animal species, including some Felidae, it has not yet been described in detail in the vulnerable Neofelis nebulosa and Panthera leo bleyenberghi and the last concern Lynx lynx and Otocolobus manul. Therefore, the present study aimed to characterize the features of the tongue surface, lingual glands and lyssa in the above-mentioned four selected wild species of the Pantherinae and Felinae subfamilies. Macroscopic, histological, histochemical and ultrastructural analyzes were used in the present work. Comparative analyzes of the dorsal tongue surface showed the presence of mechanical lingual papillae on five subtypes of filiform papillae on the apex and body and conical papillae on the root of the tongue. Gustatory papillae in the four analyzed species were fungiform papillae and various numbers of vallate papillae. Foliate papillae were absent in P. leo bleyenberghi and L. lynx, while delicate smooth folds, which were separated by parallel grooves but without taste buds, were present in N. nebulosa. The vallate and foliate papillae were accompanied by lingual glands, which produced a serous secretion, whereas the mixed lingual glands of the lingual root were with a predominance of mucus secretions comparable to four captive Felidae species. In the median plane on the ventral surface of the apex under its epithelium and within the muscle fibers, the lyssa was also observed to a varying degree, with the least developed, and thought about the size of the entire tongue, was in P. leo bleyenberghi. The lyssa structure in the four species was dominated by adipose tissue. The obtained results contribute knowledge concerning the functional anatomy of the tongue in four selected Felidae species, especially in terms of comparative anatomy. Full article

(This article belongs to the Section Physiology)

Open AccessArticle

Effectiveness of Repetitive Transcranial Magnetic Stimulation Combined with Visual Feedback Training in Improving Neuroplasticity and Lower Limb Function after Chronic Stroke: A Pilot Study

by

,

,

,

and

Biology 2023, 12(4), 515; https://doi.org/10.3390/biology12040515 (registering DOI) - 29 Mar 2023

Abstract

After a stroke, sustained gait impairment can restrict participation in the activities listed in the International Classification of Functioning, Disability, and Health model and cause poor quality of life. The present study investigated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and visual [...] Read more.

After a stroke, sustained gait impairment can restrict participation in the activities listed in the International Classification of Functioning, Disability, and Health model and cause poor quality of life. The present study investigated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and visual feedback training (VF) training in improving lower limb motor performance, gait, and corticospinal excitability in patients with chronic stroke. Thirty patients were randomized into three groups that received either rTMS or sham stimulation over the contralesional leg region accompanied by VF training groups in addition to the conventional rehabilitation group. All participants underwent intervention sessions three times per week for four weeks. Outcome measures included the motor-evoked potential (MEP) of the anterior tibialis muscle, Berg Balance Scale (BBS) scores, Timed Up and Go (TUG) test scores, and Fugl–Meyer Assessment of Lower Extremity scores. After the intervention, the rTMS and VF group had significantly improved in MEP latency (p = 0.011), TUG scores (p = 0.008), and BBS scores (p = 0.011). The sham rTMS and VF group had improved MEP latency (p = 0.027). The rTMS and VF training may enhance the cortical excitability and walking ability of individuals with chronic stroke. The potential benefits encourage a larger trial to determine the efficacy in stroke patients. Full article

(This article belongs to the Special Issue Effects of Physical Exercise on Human Physiology and Pathology)

► Show Figures

Figure 1

Open AccessReview

Improving Dietary Zinc Bioavailability Using New Food Fortification Approaches: A Promising Tool to Boost Immunity in the Light of COVID-19

by

,

,

,

and

Biology 2023, 12(4), 514; https://doi.org/10.3390/biology12040514 (registering DOI) - 29 Mar 2023

Abstract

Zinc is a powerful immunomodulatory trace element, and its deficiency in the body is closely associated with changes in immune functions and viral infections, including SARS-CoV-2, the virus responsible for COVID-19. The creation of new forms of zinc delivery to target cells can [...] Read more.

Zinc is a powerful immunomodulatory trace element, and its deficiency in the body is closely associated with changes in immune functions and viral infections, including SARS-CoV-2, the virus responsible for COVID-19. The creation of new forms of zinc delivery to target cells can make it possible to obtain smart chains of food ingredients. Recent evidence supports the idea that the optimal intake of zinc or bioactive compounds in appropriate supplements should be considered as part of a strategy to generate an immune response in the human body. Therefore, controlling the amount of this element in the diet is especially important for populations at risk of zinc deficiency, who are more susceptible to the severe progression of viral infection and disease, such as COVID-19. Convergent approaches such as micro- and nano-encapsulation develop new ways to treat zinc deficiency and make zinc more bioavailable. Full article

(This article belongs to the Special Issue Essential Trace Elements in the Human Metabolism)

► Show Figures

Graphical abstract

Open AccessArticle

Transcriptome Analysis Reveals That C17 Mycosubtilin Antagonizes Verticillium dahliae by Interfering with Multiple Functional Pathways of Fungi

by

,

,

,

,

,

,

,

,

and

Biology 2023, 12(4), 513; https://doi.org/10.3390/biology12040513 (registering DOI) - 29 Mar 2023

Abstract

Verticillium wilt is a kind of soil-borne plant fungal disease caused by Verticillium dahliae (Vd). Vd 991 is a strong pathogen causing cotton Verticillium wilt. Previously, we isolated a compound from the secondary metabolites of Bacillus subtilis J15 (BS J15), which showed a [...] Read more.

Verticillium wilt is a kind of soil-borne plant fungal disease caused by Verticillium dahliae (Vd). Vd 991 is a strong pathogen causing cotton Verticillium wilt. Previously, we isolated a compound from the secondary metabolites of Bacillus subtilis J15 (BS J15), which showed a significant control effect on cotton Verticillium wilt and was identified as C17 mycosubtilin. However, the specific fungistatic mechanism by which C17 mycosubtilin antagonizes Vd 991 is not clear. Here, we first showed that C17 mycosubtilin inhibits the growth of Vd 991 and affects germination of spores at the minimum inhibitory concentration (MIC). Morphological observation showed that C17 mycosubtilin treatment caused shrinking, sinking, and even damage to spores; the hyphae became twisted and rough, the surface was sunken, and the contents were unevenly distributed, resulting in thinning and damage to the cell membrane and cell wall and swelling of mitochondria of fungi. Flow cytometry analysis with ANNEXINV-FITC/PI staining showed that C17 mycosubtilin induces necrosis of Vd 991 cells in a time-dependent manner. Differential transcription analysis showed that C17 mycosubtilin at a semi-inhibitory concentration (IC50) treated Vd 991 for 2 and 6 h and inhibited fungal growth mainly by destroying synthesis of the fungal cell membrane and cell wall, inhibiting its DNA replication and transcriptional translation process, blocking its cell cycle, destroying fungal energy and substance metabolism, and disrupting the redox process of fungi. These results directly showed the mechanism by which C17 mycosubtilin antagonizes Vd 991, providing clues for the mechanism of action of lipopeptides and useful information for development of more effective antimicrobials. Full article

(This article belongs to the Special Issue Beneficial Microorganisms for Plants)

► Show Figures

Figure 1

Open AccessArticle

Phylogenomics and Biogeography of the Mammilloid Clade Revealed an Intricate Evolutionary History Arose in the Mexican Plateau

by

,

,

,

and

Biology 2023, 12(4), 512; https://doi.org/10.3390/biology12040512 - 29 Mar 2023

Abstract

Mexico harbors ~45% of world’s cacti species richness. Their biogeography and phylogenomics were integrated to elucidate the evolutionary history of the genera Coryphantha, Escobaria, Mammillaria, Mammilloydia, Neolloydia, Ortegocactus, and Pelecyphora (Mammilloid Clade). We analyzed 52 orthologous loci [...] Read more.

Mexico harbors ~45% of world’s cacti species richness. Their biogeography and phylogenomics were integrated to elucidate the evolutionary history of the genera Coryphantha, Escobaria, Mammillaria, Mammilloydia, Neolloydia, Ortegocactus, and Pelecyphora (Mammilloid Clade). We analyzed 52 orthologous loci from 142 complete genomes of chloroplast (103 taxa) to generate a cladogram and a chronogram; in the latter, the ancestral distribution was reconstructed with the Dispersal-Extinction-Cladogenesis model. The ancestor of these genera arose ~7 Mya on the Mexican Plateau, from which nine evolutionary lineages evolved. This region was the site of 52% of all the biogeographical processes. The lineages 2, 3 and 6 were responsible for the colonization of the arid southern territories. In the last 4 Mya, the Baja California Peninsula has been a region of prolific evolution, particularly for lineages 8 and 9. Dispersal was the most frequent process and vicariance had relevance in the isolation of cacti distributed in the south of Mexico. The 70 taxa sampled as Mammillaria were distributed in six distinct lineages; one of these presumably corresponded to this genus, which likely had its center of origin in the southern part of the Mexican Plateau. We recommend detailed studies to further determine the taxonomic circumscription of the seven genera. Full article

(This article belongs to the Special Issue Advances in Plant Taxonomy and Systematics)

► Show Figures

Figure 1

Open AccessArticle

Leucine Repeat Rich Kinase 1 Controls Osteoclast Activity by Managing Lysosomal Trafficking and Secretion

by

,

,

,

,

,

,

,

and

Biology 2023, 12(4), 511; https://doi.org/10.3390/biology12040511 - 29 Mar 2023

Abstract

We previously demonstrated that mice with targeted deletion of the leucine repeat rich kinase 1 (Lrrk1) gene were osteopetrotic due to the failure of osteoclasts to resorb bone. To determine how LRRK1 regulates osteoclast activity, we examined the intracellular and extracellular [...] Read more.

We previously demonstrated that mice with targeted deletion of the leucine repeat rich kinase 1 (Lrrk1) gene were osteopetrotic due to the failure of osteoclasts to resorb bone. To determine how LRRK1 regulates osteoclast activity, we examined the intracellular and extracellular acidification with an acidotropic probe, acridine orange, in live osteoclasts on bone slices. We examined lysosome distribution in osteoclasts by localization of LAMP-2, cathepsin K, and v-ATPase by immunofluorescent staining with specific antibodies. We found that both vertical and horizontal cross-sectional images of the wild-type (WT) osteoclasts showed orange-staining of the intracellular acidic vacuoles/lysosomes dispersed to the ruffled border. By contrast, the LRRK1 deficient osteoclasts exhibited fluorescent orange staining in the cytoplasm away from the extracellular lacunae because of an altered distribution of the acidic vacuoles/lysosomes. In addition, WT osteoclasts displayed a peripheral distribution of LAMP-2 positive lysosomes with a typical actin ring. The clustered F-actin constitutes a peripheral sealing zone and a ruffled border which was stretched out into a resorption pit. The LAMP-2 positive lysosomes were also distributed to the sealing zone, and the cell was associated with a resorption pit. By contrast, LRRK1-deficient osteoclasts showed diffused F-actin throughout the cytoplasm. The sealing zone was weak and not associated with a resorption pit. LAMP-2 positive lysosomes were also diffuse in the cytoplasm and were not distributed to the ruffled border. Although the LRRK1-deficient osteoclast expressed normal levels of cathepsin K and v-ATPase, the lysosomal-associated cathepsin K and v-ATPase were not accumulated at the ruffled border in Lrrk1 KO osteoclasts. Our data indicate that LRRK1 controls osteoclast activity by regulating lysosomal distribution, acid secretion, and protease exocytosis. Full article

(This article belongs to the Section Cell Biology)

► Show Figures

Figure 1

Open AccessArticle

Identification and Functional Analysis of Known and New Mutations in the Transcription Factor KLF1 Linked with β-Thalassemia-like Phenotypes

by

,

,

,

,

,

,

and

Biology 2023, 12(4), 510; https://doi.org/10.3390/biology12040510 - 28 Mar 2023

Abstract

The erythroid transcriptional factor Krüppel-like factor 1 (KLF1) is a master regulator of erythropoiesis. Mutations that cause KLF1 haploinsufficiency have been linked to increased fetal hemoglobin (HbF) and hemoglobin A₂ (HbA₂) levels with ameliorative effects on the severity of β-thalassemia. [...] Read more.

The erythroid transcriptional factor Krüppel-like factor 1 (KLF1) is a master regulator of erythropoiesis. Mutations that cause KLF1 haploinsufficiency have been linked to increased fetal hemoglobin (HbF) and hemoglobin A₂ (HbA₂) levels with ameliorative effects on the severity of β-thalassemia. With the aim of determining if KLF1 gene variations might play a role in the modulation of β-thalassemia, in this study we screened 17 subjects showing a β-thalassemia-like phenotype with a slight or marked increase in HbA₂ and HbF levels. Overall, seven KLF1 gene variants were identified, of which two were novel. Functional studies were performed in K562 cells to clarify the pathogenic significance of these mutations. Our study confirmed the ameliorative effect on the thalassemia phenotype for some of these variants but also raised the notion that certain mutations may have deteriorating effects by increasing KLF1 expression levels or enhancing its transcriptional activity. Our results indicate that functional studies are required to evaluate the possible effects of KLF1 mutations, particularly in the case of the co-existence of two or more mutations that could differently contribute to KLF1 expression or transcriptional activity and consequently to the thalassemia phenotype. Full article

(This article belongs to the Special Issue Thalassemia Research: Focus on Novel Molecular Insights and Clinical Perspectives)

► Show Figures

Graphical abstract

Open AccessArticle

Assessing Global Efforts in the Selection of Vertebrates as Umbrella Species for Conservation

by

,

,

,

,

,

and

Biology 2023, 12(4), 509; https://doi.org/10.3390/biology12040509 - 28 Mar 2023

Abstract

The umbrella-species strategy has been proposed as an attainable tool to achieve multi-species and community conservation with limited investment. There have been many umbrella-related studies since the concept’s inception; thus, a summary of global study efforts and recommended umbrella species is important for [...] Read more.

The umbrella-species strategy has been proposed as an attainable tool to achieve multi-species and community conservation with limited investment. There have been many umbrella-related studies since the concept’s inception; thus, a summary of global study efforts and recommended umbrella species is important for understanding advances in the field and facilitating conservation applications. Here, we collated 213 recommended umbrella species of terrestrial vertebrates from 242 scientific articles published during 1984–2021 and analyzed their geographic patterns, biological features, and conservation statuses to identify global trends in the selection of umbrella species. We found a considerable geographic bias: most studies and, consequently, recommended umbrella species are from the Northern Hemisphere. There is also a strong taxonomic bias, with grouses (order Galliformes) and large carnivores being the most popular umbrella species and amphibians and reptiles being largely overlooked. In addition, wide-ranging and non-threatened species were frequently recommended as umbrella species. Given the observed biases and trends, we caution that appropriate species need to be chosen for each location, and it is important to confirm that popular, wide-ranging species are effective umbrella species. Moreover, amphibians and reptiles should be investigated for their potential as umbrella species. The umbrella-species strategy has many strengths and, if applied appropriately, may be one of the best options in today’s conservation research and funding landscape. Full article

(This article belongs to the Section Conservation Biology and Biodiversity)

► Show Figures

Figure 1

Open AccessReview

Inputs and Outputs of the Mammalian Circadian Clock

by

Ashley N. Starnes

and

Jeff R. Jones

Biology 2023, 12(4), 508; https://doi.org/10.3390/biology12040508 - 28 Mar 2023

Abstract

Circadian rhythms in mammals are coordinated by the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Light and other environmental inputs change the timing of the SCN neural network oscillator, which, in turn, sends output signals that entrain daily behavioral and physiological rhythms. While [...] Read more.

Circadian rhythms in mammals are coordinated by the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Light and other environmental inputs change the timing of the SCN neural network oscillator, which, in turn, sends output signals that entrain daily behavioral and physiological rhythms. While much is known about the molecular, neuronal, and network properties of the SCN itself, the circuits linking the outside world to the SCN and the SCN to rhythmic outputs are understudied. In this article, we review our current understanding of the synaptic and non-synaptic inputs onto and outputs from the SCN. We propose that a more complete description of SCN connectivity is needed to better explain how rhythms in nearly all behaviors and physiological processes are generated and to determine how, mechanistically, these rhythms are disrupted by disease or lifestyle. Full article

(This article belongs to the Special Issue Frontiers in Mammalian Circadian Biology)

► Show Figures

Figure 1

Open AccessArticle

Are Portuguese Cowpea Genotypes Adapted to Drought? Phenological Development and Grain Quality Evaluation

by

,

,

,

,

,

,

,

and

Biology 2023, 12(4), 507; https://doi.org/10.3390/biology12040507 - 27 Mar 2023

Abstract

Along with population growth, global climate change represents a critical threat to agricultural production, compromising the goal of achieving food and nutrition security for all. It is urgent to create sustainable and resilient agri-food systems capable of feeding the world without debilitating the [...] Read more.

Along with population growth, global climate change represents a critical threat to agricultural production, compromising the goal of achieving food and nutrition security for all. It is urgent to create sustainable and resilient agri-food systems capable of feeding the world without debilitating the planet. The Food and Agriculture Organization of the United Nations (FAO) refers to pulses as a superfood, as one of the most nutritious crops with high health benefits. Considered to be low-cost, many can be produced in arid lands and have an extended shelf-life. Their cultivation helps reduce greenhouse gases and increases carbon sequestration, also improving soil fertility. Cowpea, Vigna unguiculata (L.) Walp. is particularly drought tolerant, with a wide diversity of landraces adapted to different environments. Considering the importance of knowing and valuing the genetic variability of this species in Portugal, this study assessed the impact of drought on four landraces of cowpea (L1 to L4) from different regions of the country and a national commercial variety (CV) as a reference. The development and evaluation of morphological characteristics were monitored in response to terminal drought (imposed during the reproductive phase), and its effects were evaluated on the yield and quality of the produced grain, namely the weight of 100 grains, color, protein content, and soluble sugars. Under drought conditions, the landraces L1 and L2 showed early maturation as a strategy to avoid water deficit. Morphological alteration of the aerial part of the plants was evident in all genotypes, with a rapid reduction in the number of leaves and a reduction in the number of flowers and pods by between 44 and 72%. The parameters of grain quality, the weight of 100 grains, color, protein, and soluble sugars did not vary significantly, except for sugars of the raffinose family that is associated with the adaptive mechanisms of plants to drought. The performance and maintenance of the evaluated characteristics reflect the adaptation acquired in the past by exposure to the Mediterranean climate, highlighting the potential agronomic and genetic value, still little exploited, that could contribute to production stability, preserved nutritional value, and food safety under water stress. Full article

► Show Figures

Graphical abstract

Open AccessArticle

Kanamycin and Ofloxacin Activate the Intrinsic Resistance to Multiple Antibiotics in Mycobacterium smegmatis

by

,

,

,

,

,

and

Biology 2023, 12(4), 506; https://doi.org/10.3390/biology12040506 - 27 Mar 2023

Abstract

Drug resistance (DR) in Mycobacterium tuberculosis is the main problem in fighting tuberculosis (TB). This pathogenic bacterium has several types of DR implementation: acquired and intrinsic DR. Recent studies have shown that exposure to various antibiotics activates multiple genes, including genes responsible for [...] Read more.

Drug resistance (DR) in Mycobacterium tuberculosis is the main problem in fighting tuberculosis (TB). This pathogenic bacterium has several types of DR implementation: acquired and intrinsic DR. Recent studies have shown that exposure to various antibiotics activates multiple genes, including genes responsible for intrinsic DR. To date, there is evidence of the acquisition of resistance at concentrations well below the standard MICs. In this study, we aimed to investigate the mechanism of intrinsic drug cross-resistance induction by subinhibitory concentrations of antibiotics. We showed that pretreatment of M. smegmatis with low doses of antibiotics (kanamycin and ofloxacin) induced drug resistance. This effect may be caused by a change in the expression of transcriptional regulators of the mycobacterial resistome, in particular the main transcriptional regulator whiB7. Full article

(This article belongs to the Special Issue Antibiotic Resistance: Linking Phenotypes and Mechanisms)

► Show Figures

Figure 1

Open AccessReview

Molecular Mechanisms and Clinical Phenotypes of GJB2 Missense Variants

by

,

,

,

,

,

,

,

,

and

Biology 2023, 12(4), 505; https://doi.org/10.3390/biology12040505 - 27 Mar 2023

Abstract

The GJB2 gene is the most common gene responsible for hearing loss (HL) worldwide, and missense variants are the most abundant type. GJB2 pathogenic missense variants cause nonsyndromic HL (autosomal recessive and dominant) and syndromic HL combined with skin diseases. However, the mechanism [...] Read more.

The GJB2 gene is the most common gene responsible for hearing loss (HL) worldwide, and missense variants are the most abundant type. GJB2 pathogenic missense variants cause nonsyndromic HL (autosomal recessive and dominant) and syndromic HL combined with skin diseases. However, the mechanism by which these different missense variants cause the different phenotypes is unknown. Over 2/3 of the GJB2 missense variants have yet to be functionally studied and are currently classified as variants of uncertain significance (VUS). Based on these functionally determined missense variants, we reviewed the clinical phenotypes and investigated the molecular mechanisms that affected hemichannel and gap junction functions, including connexin biosynthesis, trafficking, oligomerization into connexons, permeability, and interactions between other coexpressed connexins. We predict that all possible GJB2 missense variants will be described in the future by deep mutational scanning technology and optimizing computational models. Therefore, the mechanisms by which different missense variants cause different phenotypes will be fully elucidated. Full article

(This article belongs to the Special Issue Gap Junctions and Connexins in Physiology, Pharmacology and Disease)

► Show Figures

Figure 1

Open AccessArticle

Diminishing the Pathogenesis of the Food-Borne Pathogen Serratia marcescens by Low Doses of Sodium Citrate

by

,

,

,

,

,

,

,

and

Biology 2023, 12(4), 504; https://doi.org/10.3390/biology12040504 - 26 Mar 2023

Abstract

Protecting food from bacterial contamination is crucial for ensuring its safety and avoiding foodborne illness. Serratia marcescens is one of the food bacterial contaminants that can form biofilms and pigments that spoil the food product and could cause infections and illness to the [...] Read more.

Protecting food from bacterial contamination is crucial for ensuring its safety and avoiding foodborne illness. Serratia marcescens is one of the food bacterial contaminants that can form biofilms and pigments that spoil the food product and could cause infections and illness to the consumer. Food preservation is essential to diminish such bacterial contaminants or at least reduce their pathogenesis; however, it should not affect food odor, taste, and consistency and must be safe. Sodium citrate is a well-known safe food additive and the current study aims to evaluate its anti-virulence and anti-biofilm activity at low concentrations against S. marcescens. The anti-virulence and antibiofilm activities of sodium citrate were evaluated phenotypically and genotypically. The results showed the significant effect of sodium citrate on decreasing the biofilm formation and other virulence factors, such as motility and the production of prodigiosin, protease, and hemolysins. This could be owed to its downregulating effect on the virulence-encoding genes. An in vivo investigation was conducted on mice and the histopathological examination of isolated tissues from the liver and kidney of mice confirmed the anti-virulence activity of sodium citrate. In addition, an in silico docking study was conducted to evaluate the sodium citrate binding ability to S. marcescens quorum sensing (QS) receptors that regulates its virulence. Sodium citrate showed a marked virtual ability to compete on QS proteins, which could explain sodium citrate’s anti-virulence effect. In conclusion, sodium citrate is a safe food additive and can be used at low concentrations to prevent contamination and biofilm formation by S. marcescens and other bacteria. Full article

(This article belongs to the Special Issue Microbial Contamination and Food Safety)

► Show Figures

Figure 1

Open AccessReview

Strategies for Improving Vascularization in Kidney Organoids: A Review of Current Trends

by

Ran Konoe

and

Ryuji Morizane

Biology 2023, 12(4), 503; https://doi.org/10.3390/biology12040503 - 26 Mar 2023

Abstract

Kidney organoids possess the potential to revolutionize the treatment of renal diseases. However, their growth and maturation are impeded by insufficient growth of blood vessels. Through a PubMed search, we have identified 34 studies that attempted to address this challenge. Researchers are exploring [...] Read more.

Kidney organoids possess the potential to revolutionize the treatment of renal diseases. However, their growth and maturation are impeded by insufficient growth of blood vessels. Through a PubMed search, we have identified 34 studies that attempted to address this challenge. Researchers are exploring various approaches including animal transplantation, organ-on-chips, and extracellular matrices (ECMs). The most prevalent method to promote the maturation and vascularization of organoids involves transplanting them into animals for in vivo culture, creating an optimal environment for organoid growth and the development of a chimeric vessel network between the host and organoids. Organ-on-chip technology permits the in vitro culture of organoids, enabling researchers to manipulate the microenvironment and investigate the key factors that influence organoid development. Lastly, ECMs have been discovered to aid the formation of blood vessels during organoid differentiation. ECMs from animal tissue have been particularly successful, although the underlying mechanisms require further research. Future research building upon these recent studies may enable the generation of functional kidney tissues for replacement therapies. Full article

(This article belongs to the Section Cell Biology)

► Show Figures

Figure 1

Open AccessReview

An Organismal Perspective on the Warburg Effect and Models for Proliferation Studies

by

Neil W. Blackstone

and

Weam S. El Rahmany

Biology 2023, 12(4), 502; https://doi.org/10.3390/biology12040502 - 26 Mar 2023

Abstract

Interest in the physiology of proliferation has been generated by human proliferative diseases, i.e., cancers. A vast literature exists on the Warburg effect, which is characterized by aerobic glycolysis, diminished oxygen uptake, and lactate secretion. While these features could be rationalized via the [...] Read more.

Interest in the physiology of proliferation has been generated by human proliferative diseases, i.e., cancers. A vast literature exists on the Warburg effect, which is characterized by aerobic glycolysis, diminished oxygen uptake, and lactate secretion. While these features could be rationalized via the production of biosynthetic precursors, lactate secretion does not fit this paradigm, as it wastes precursors. Forming lactate from pyruvate allows for reoxidizing cytosolic NADH, which is crucial for continued glycolysis and may allow for maintaining large pools of metabolic intermediates. Alternatively, lactate production may not be adaptive, but rather reflect metabolic constraints. A broader sampling of the physiology of proliferation, particularly in organisms that could reoxidize NADH using other pathways, may be necessary to understand the Warburg effect. The best-studied metazoans (e.g., worms, flies, and mice) may not be suitable, as they undergo limited proliferation before initiating meiosis. In contrast, some metazoans (e.g., colonial marine hydrozoans) exhibit a stage in the life cycle (the polyp stage) that only undergoes mitotic proliferation and never carries out meiosis (the medusa stage performs this). Such organisms are prime candidates for general studies of proliferation in multicellular organisms and could at least complement the short-generation models of modern biology. Full article

► Show Figures

Figure 1

Open AccessArticle

Effect of Rice Straw and Stubble Burning on Soil Physicochemical Properties and Bacterial Communities in Central Thailand

by

,

,

,

and

Biology 2023, 12(4), 501; https://doi.org/10.3390/biology12040501 - 26 Mar 2023

Abstract

Rice straw and stubble burning is widely practiced to clear fields for new crops. However, questions remain about the effects of fire on soil bacterial communities and soil properties in paddy fields. Here, five adjacent farmed fields were investigated in central Thailand to [...] Read more.

Rice straw and stubble burning is widely practiced to clear fields for new crops. However, questions remain about the effects of fire on soil bacterial communities and soil properties in paddy fields. Here, five adjacent farmed fields were investigated in central Thailand to assess changes in soil bacterial communities and soil properties after burning. Samples of soil prior to burning, immediately after burning, and 1 year after burning were obtained from depths of 0 to 5 cm. The results showed that the pH, electrical conductivity, NH₄-N, total nitrogen, and soil nutrients (available P, K, Ca, and Mg) significantly increased immediately after burning due to an increased ash content in the soil, whereas NO₃-N decreased significantly. However, these values returned to the initial values. Chloroflexi were the dominant bacteria, followed by Actinobacteria and Proteobacteria. At 1 year after burning, Chloroflexi abundance decreased remarkably, whereas Actinobacteria, Proteobacteria, Verrucomicrobia, and Gemmatimonadetes abundances significantly increased. Bacillus, HSB OF53-F07, Conexibacter, and Acidothermus abundances increased immediately after burning, but were lower 1 year after burning. These bacteria may be highly resistant to heat, but grow slowly. Anaeromyxobacter and Candidatus Udaeobacter dominated 1 year after burning, most likely because of their rapid growth and the fact that they occupy areas with increased soil nutrient levels after fires. Amidase, cellulase, and chitinase levels increased with increased organic matter levels, whereas β-glucosidase, chitinase, and urease levels positively correlated with the soil total nitrogen level. Although clay and soil moisture strongly correlated with the soil bacterial community’s composition, negative correlations were found for β-glucosidase, chitinase, and urease. In this study, rice straw and standing stubble were burnt under high soil moisture and within a very short time, suggesting that the fire was not severe enough to raise the soil temperature and change the soil microbial community immediately after burning. However, changes in soil properties due to ash significantly increased the diversity indices, which was noticeable 1 year after burning. Full article

(This article belongs to the Special Issue Biodiversity and Ecosystem Functioning in Naturally and Experimentally Assembled Communities)

► Show Figures

Figure 1

Journal Description

Biology

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI