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Life, Volume 11, Issue 2 (February 2021) – 105 articles

Cover Story (view full-size image): The HIV-1 capsid protein is an essential structural component that facilitates many crucial viral replication steps through interactions with numerous host cell factors. This review discusses the details of these interactions, their functional implications within the viral life cycle, and the potential of capsid as a therapeutic target. View this paper.
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Open AccessCommunication
Proteomic Insight into the Symbiotic Relationship of Pinus massoniana Lamb and Suillus luteus towards Developing Al-Stress Resistance
Life 2021, 11(2), 177; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020177 - 23 Feb 2021
Viewed by 383
Abstract
Global warming significantly impacts forest range areas by increasing soil acidification or aluminum toxicity. Aluminum (Al) toxicity retards plant growth by inhibiting the root development process, hindering water uptake, and limiting the bioavailability of other essential micronutrients. Pinus massoniana (masson pine), globally recognized [...] Read more.
Global warming significantly impacts forest range areas by increasing soil acidification or aluminum toxicity. Aluminum (Al) toxicity retards plant growth by inhibiting the root development process, hindering water uptake, and limiting the bioavailability of other essential micronutrients. Pinus massoniana (masson pine), globally recognized as a reforestation plant, is resistant to stress conditions including biotic and abiotic stresses. This resistance is linked to the symbiotic relationship with diverse ectomycorrhizal fungal species. In the present study, we investigated the genetic regulators as expressed proteins, conferring a symbiotic relationship between Al-stress resistance and Suillus luteus in masson pine. Multi-treatment trials resulted in the identification of 12 core Al-stress responsive proteins conserved between Al stress conditions with or without S. luteus inoculation. These proteins are involved in chaperonin CPN60-2, protein refolding and ATP-binding, Cu-Zn-superoxide dismutase precursor, oxidation-reduction process, and metal ion binding, phosphoglycerate kinase 1, glycolytic process, and metabolic process. Furthermore, 198 Al responsive proteins were identified specifically under S. luteus-inoculation and are involved in gene regulation, metabolic process, oxidation-reduction process, hydrolase activity, and peptide activity. Chlorophyll a-b binding protein, endoglucanase, putative spermidine synthase, NADH dehydrogenase, and glutathione-S-transferase were found with a significant positive expression under a combined Al and S. luteus treatment, further supported by the up-regulation of their corresponding genes. This study provides a theoretical foundation for exploiting the regulatory role of ectomycorrhizal inoculation and associated genetic changes in resistance against Al stress in masson pine. Full article
(This article belongs to the Special Issue Plant Proteomics)
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Open AccessArticle
Effects of Schlemm’s Canal Expansion: Biomechanics and MIGS Implications
Life 2021, 11(2), 176; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020176 - 23 Feb 2021
Viewed by 343
Abstract
Objective: To evaluate the change of biomechanical properties of the trabecular meshwork (TM) and configuration of collector channels (CC) by high-resolution optical coherence tomography (HR-OCT) induced by Schlemm’s canal (SC) dilation. Methods: The anterior segments of two human eyes were divided into four [...] Read more.
Objective: To evaluate the change of biomechanical properties of the trabecular meshwork (TM) and configuration of collector channels (CC) by high-resolution optical coherence tomography (HR-OCT) induced by Schlemm’s canal (SC) dilation. Methods: The anterior segments of two human eyes were divided into four quadrants. One end of a specially designed cannula was placed in SC and the other end connected to a perfusion reservoir. HR-OCT provided three-dimensional (3D) volumetric and two-dimensional (2D) cross-sectional imaging permitting assessment of the biomechanical properties of the TM. A large fluid bolus was introduced into SC. Same-sample, pre and post deformation and disruption of SC and CC lumen areas were analyzed. Results: Morphologic 3D reconstructions documented pressure-dependent changes in lumen dimension of SC, CC, and circumferential intrascleral channels. 2D imaging established volumetric stress-strain curves (elastance curves) of the TM in quadrants. The curves of TM elastance shift to the right with an increase in pressure-dependent steady-state SC area. After a bolus disruption, the SC area increased, while the CC area decreased. Conclusion: Our experimental setup permits the study of the biomechanical properties of TM by examining elastance, which differs segmentally and is altered by mechanical expansion of SC by a fluid bolus. The study may shed light on mechanisms of intraocular pressure control of some glaucoma surgery. Full article
(This article belongs to the Special Issue Biomechanical Imaging in Ophthalmology)
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Open AccessArticle
Metabolic Phenotypes and Chronic Kidney Disease: A Cross-Sectional Assessment of Patients from a Large Federally Qualified Health Center
Life 2021, 11(2), 175; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020175 - 23 Feb 2021
Viewed by 777
Abstract
The purpose of this study is to determine if renal function varies by metabolic phenotype. A total of 9599 patients from a large Federally Qualified Health Center (FQHC) were included in the analysis. Metabolic health was classified as the absence of metabolic abnormalities [...] Read more.
The purpose of this study is to determine if renal function varies by metabolic phenotype. A total of 9599 patients from a large Federally Qualified Health Center (FQHC) were included in the analysis. Metabolic health was classified as the absence of metabolic abnormalities defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, excluding waist circumference. Obesity was defined as body mass index >30 kg/m2 and renal health as an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2. Linear and logistic regressions were used to analyze the data. The metabolically healthy overweight (MHO) phenotype had the highest eGFR (104.86 ± 28.76 mL/min/1.72 m2) and lowest unadjusted odds of chronic kidney disease (CKD) (OR = 0.46, 95%CI = 0.168, 1.267, p = 0.133), while the metabolically unhealthy normal weight (MUN) phenotype demonstrated the lowest eGFR (91.34 ± 33.28 mL/min/1.72 m2) and the highest unadjusted odds of CKD (OR = 3.63, p < 0.0001). After controlling for age, sex, and smoking status, the metabolically unhealthy obese (MUO) (OR = 1.80, 95%CI = 1.08, 3.00, p = 0.024) was the only phenotype with significantly higher odds of CKD as compared to the reference. We demonstrate that the metabolically unhealthy phenotypes have the highest odds of CKD compared to metabolically healthy individuals. Full article
(This article belongs to the Special Issue Research Updates in Chronic Kidney Disease)
Open AccessArticle
Single Nucleotide Polymorphism in the IL17A Gene Is Associated with Interstitial Lung Disease Positive to Anti-Jo1 Antisynthetase Autoantibodies
Life 2021, 11(2), 174; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020174 - 23 Feb 2021
Viewed by 527
Abstract
Antisynthetase syndrome (ASSD) is a rare multisystemic connective tissue disease affecting the skin, joints, muscles, and lungs, characterized by anti-aminoacyl transfer-RNA-synthetases (anti-tRNA) autoantibodies production, being anti-Jo1 the most frequent. We included one-hundred twenty-one ASSD patients and 340 healthy subjects (HS), and also, we [...] Read more.
Antisynthetase syndrome (ASSD) is a rare multisystemic connective tissue disease affecting the skin, joints, muscles, and lungs, characterized by anti-aminoacyl transfer-RNA-synthetases (anti-tRNA) autoantibodies production, being anti-Jo1 the most frequent. We included one-hundred twenty-one ASSD patients and 340 healthy subjects (HS), and also, we divided the case group into anti-Jo1 and non-anti-Jo1. Two single nucleotide polymorphisms (SNPs) in the IL17A gene were evaluated. Anti-Jo1 was the most common anti-tRNA antibody in our cohort, and the most frequent tomographic pattern was non-specific interstitial pneumonia (NSIP). Anti-Jo1 ASSD patients had higher levels of creatine phosphokinase than the non-anti-Jo1 group. Significant differences in genotype frequencies with rs8193036/CC between anti-Jo1 vs. non-anti-Jo1 ASSD patients (p < 0.001), maintaining the association after Bonferroni correction (p = 0.002). Additionally, in the anti-Jo1 group vs. HS comparison, we found a statistically significant difference with the same SNP (p = 0.018, OR = 2.91, 95% CI = 1.15–7.35), maintaining the association after Bonferroni correction (p = 0.036). The rs8193036/CC genotype in IL17A is associated with ASSD patients with anti-Jo1. Also, anti-Jo1 and non-anti-Jo1 patients display differences in genotype frequencies. Full article
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Open AccessReview
Sarcopenia and Cognitive Function: Role of Myokines in Muscle Brain Cross-Talk
Life 2021, 11(2), 173; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020173 - 23 Feb 2021
Viewed by 1080
Abstract
Sarcopenia is a geriatric syndrome characterized by the progressive degeneration of muscle mass and function, and it is associated with severe complications, which are falls, functional decline, frailty, and mortality. Sarcopenia is associated with cognitive impairment, defined as a decline in one or [...] Read more.
Sarcopenia is a geriatric syndrome characterized by the progressive degeneration of muscle mass and function, and it is associated with severe complications, which are falls, functional decline, frailty, and mortality. Sarcopenia is associated with cognitive impairment, defined as a decline in one or more cognitive domains as language, memory, reasoning, social cognition, planning, making decisions, and solving problems. Although the exact mechanism relating to sarcopenia and cognitive function has not yet been defined, several studies have shown that skeletal muscle produces and secrete molecules, called myokines, that regulate brain functions, including mood, learning, locomotor activity, and neuronal injury protection, showing the existence of muscle-brain cross-talk. Moreover, studies conducted on physical exercise supported the existence of muscle-brain cross-talk, showing how physical activity, changing myokines' circulating levels, exerts beneficial effects on the brain. The review mainly focuses on describing the role of myokines on brain function and their involvement in cognitive impairment in sarcopenia. Full article
(This article belongs to the Special Issue Sarcopenia and Liver Disease: Current and Future Perspectives)
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Open AccessArticle
Integrative Analysis Identified Key Schizophrenia Risk Factors from an Abnormal Behavior Mouse Gene Set
Life 2021, 11(2), 172; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020172 - 23 Feb 2021
Viewed by 433
Abstract
Schizophrenia (SCZ) is a severe chronic psychiatric illness with heterogeneous symptoms. However, the pathogenesis of SCZ is unclear, and the number of well-defined SCZ risk factors is limited. We hypothesized that an abnormal behavior (AB) gene set verified by mouse model experiments can [...] Read more.
Schizophrenia (SCZ) is a severe chronic psychiatric illness with heterogeneous symptoms. However, the pathogenesis of SCZ is unclear, and the number of well-defined SCZ risk factors is limited. We hypothesized that an abnormal behavior (AB) gene set verified by mouse model experiments can be used to better understand SCZ risks. In this work, we carried out an integrative bioinformatics analysis to study two types of risk genes that are either differentially expressed (DEGs) in the case-control study data or carry reported SCZ genetic variants (MUTs). Next, we used RNA-Seq expression data from the hippocampus (HIPPO) and dorsolateral prefrontal cortex (DLPFC) to define the key genes affected by different types (DEGs and MUTs) in different brain regions (DLPFC and HIPPO): DLPFC-kDEG, DLPFC-kMUT, HIPPO-kDEG, and HIPPO-kMUT. The four hub genes (SHANK1, SHANK2, DLG4, and NLGN3) of the biological functionally enriched terms were strongly linked to SCZ via gene co-expression network analysis. Then, we observed that specific spatial expressions of DLPFC-kMUT and HIPPO-kMUT were convergent in the early stages and divergent in the later stages of development. In addition, all four types of key genes showed significantly larger average protein–protein interaction degrees than the background. Comparing the different cell types, the expression of four types of key genes showed specificity in different dimensions. Together, our results offer new insights into potential risk factors and help us understand the complexity and regional heterogeneity of SCZ. Full article
(This article belongs to the Special Issue Multi-Omics for the Understanding of Brain Diseases)
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Open AccessArticle
Management of Infants with Brief Resolved Unexplained Events (BRUE) and Apparent Life-Threatening Events (ALTE): A RAND/UCLA Appropriateness Approach
Life 2021, 11(2), 171; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020171 - 22 Feb 2021
Viewed by 515
Abstract
Unexpected events of breath, tone, and skin color change in infants are a cause of considerable distress to the caregiver and there is still debate on their appropriate management. The aim of this study is to survey the trend in prevention, decision-making, and [...] Read more.
Unexpected events of breath, tone, and skin color change in infants are a cause of considerable distress to the caregiver and there is still debate on their appropriate management. The aim of this study is to survey the trend in prevention, decision-making, and management of brief resolved unexplained events (BRUE)/apparent life-threatening events (ALTE) and to develop a shared protocol among hospitals and primary care pediatricians regarding hospital admission criteria, work-up and post-discharge monitoring of patients with BRUE/ALTE. For the study purpose, a panel of 54 experts was selected to achieve consensus using the RAND/UCLA appropriateness method. Twelve scenarios were developed: one addressed to primary prevention of ALTE and BRUE, and 11 focused on hospital management of BRUE and ALTE. For each scenario, participants were asked to rank each option from ‘1’ (extremely inappropriate) to ‘9’ (extremely appropriate). Results derived from panel meeting and discussion showed several points of agreement but also disagreement with different opinion emerged and the need of focused education on some areas. However, by combining previous recommendations with expert opinion, the application of the RAND/UCLA appropriateness permitted us to drive pediatricians to reasoned and informed decisions in term of evaluation, treatment and follow-up of infants with BRUE/ALTE, reducing inappropriate exams and hospitalisation and highlighting priorities for educational interventions. Full article
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Open AccessArticle
Radiomics Analysis for 177Lu-DOTAGA-(l-y)fk(Sub-KuE) Targeted Radioligand Therapy Dosimetry in Metastatic Prostate Cancer—A Model Based on Clinical Example
Life 2021, 11(2), 170; https://doi.org/10.3390/life11020170 - 22 Feb 2021
Viewed by 475
Abstract
177Lu-DOTAGA-(l-y)fk(Sub-KuE) a.k.a. 177Lu-PSMA I&T is currently used for radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) in several centers in Europe. Background: Dosimetry is mandatory according to EU guidelines, although routine methods for dosimetry, i.e., absorbed radiation dose calculations for [...] Read more.
177Lu-DOTAGA-(l-y)fk(Sub-KuE) a.k.a. 177Lu-PSMA I&T is currently used for radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) in several centers in Europe. Background: Dosimetry is mandatory according to EU guidelines, although routine methods for dosimetry, i.e., absorbed radiation dose calculations for radiopharmaceuticals, are missing. Methods: We created a model of dosimetric analysis utilizing voxel-based dosimetry and intra-lesion radiomics to assess their practicality in routine dosimetry. Results: As an example for the model, our patient with mCRPC had excellent therapy response; quantitatively more than 97% of the metastatic tumor burden in local and distant lymph nodes and skeleton was destroyed by four cycles of RLT. The absorbed radiation doses in metastases decreased towards later cycles of RLT. Besides the change of prostate-specific membrane antigen (PSMA) concentration and absorbed doses in the tumor, further response to RLT could be predicted from biomarker changes, such as LDH and PSA. Conclusions: Individual dosimetry is needed to understand large variations in tumor doses and mixed responses; for that purpose, routine tools should be developed. The Dosimetry Research Tool (DRT) fluently performed automated organ delineation and absorbed radiation dose calculations in normal organs, and the results in our patient were in good concordance with the published studies on 177Lu-PSMA dosimetry. At the same time, we experienced considerable challenges in voxel-based dosimetry of tumor lesions. Measurements of 177Lu-PSMA activity concentrations instead of absorbed radiation dose calculations could make routine dosimetry more flexible. The first cycle of RLT seems to have quantitatively the biggest impact on the therapy effect. Radiomics analyses could probably aid in the treatment optimization, but it should be tested in large patient populations. Full article
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Open AccessReview
HBV/HDV Co-Infection: Epidemiological and Clinical Changes, Recent Knowledge and Future Challenges
Life 2021, 11(2), 169; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020169 - 22 Feb 2021
Viewed by 493
Abstract
Several investigations have been published on Hepatitis Delta Virus (HDV) infection in recent years, from which we have drawn the salient data to provide readers with useful information to improve their knowledge on the subject. HDV genotypes 5–8 have been recently imported to [...] Read more.
Several investigations have been published on Hepatitis Delta Virus (HDV) infection in recent years, from which we have drawn the salient data to provide readers with useful information to improve their knowledge on the subject. HDV genotypes 5–8 have been recently imported to Western countries from central Africa, whose clinical relevance deserves further investigation. Ongoing HDV replication has been identified as an independent predictor of progression to cirrhosis and HCC for patients with HDV chronic hepatitis (HDV-CH). Long-term treatments of HDV-CH with standard or pegylated interferon alfa (peg-IFN-α) have all been unsatisfactory, leading to a sustained virological response (SVR) only in 20–30% of patients treated, faced with a poor tolerability and frequent serious adverse reactions; the addition of HBV nucleo(s)tide analogues to peg-IFN- α did not improve the rate of SVR. The improved knowledge of the HDV life cycle has allowed the development of direct acting agents towards key-points of the HDV life cycle, namely bulevirtide, lonafarnib and nucleic acid polymers. Preliminary data have shown that these drugs are more effective than interferon-based therapies, but adverse reactions are also common, which however seem toned down in combination therapy with other antivirals. Full article
(This article belongs to the Special Issue The New Challenges in Infectious Diseases)
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Open AccessArticle
RNase A Domain-Swapped Dimers Produced Through Different Methods: Structure–Catalytic Properties and Antitumor Activity
Life 2021, 11(2), 168; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020168 - 21 Feb 2021
Viewed by 358
Abstract
Upon oligomerization, RNase A can acquire important properties, such as cytotoxicity against leukemic cells. When lyophilized from 40% acetic acid solutions, the enzyme self-associates through the so-called three-dimensional domain swapping (3D-DS) mechanism involving both N- and/or C-terminals. The same species are formed if [...] Read more.
Upon oligomerization, RNase A can acquire important properties, such as cytotoxicity against leukemic cells. When lyophilized from 40% acetic acid solutions, the enzyme self-associates through the so-called three-dimensional domain swapping (3D-DS) mechanism involving both N- and/or C-terminals. The same species are formed if the enzyme is subjected to thermal incubation in various solvents, especially in 40% ethanol. We evaluated here if significant structural modifications might occur in RNase A N- or C-swapped dimers and/or in the residual monomer(s), as a function of the oligomerization protocol applied. We detected that the monomer activity vs. ss-RNA was partly affected by both protocols, although the protein does not suffer spectroscopic alterations. Instead, the two N-swapped dimers showed differences in the fluorescence emission spectra but almost identical enzymatic activities, while the C-swapped dimers displayed slightly different activities vs. both ss- or ds-RNA substrates together with not negligible fluorescence emission alterations within each other. Besides these results, we also discuss the reasons justifying the different relative enzymatic activities displayed by the N-dimers and C-dimers. Last, similarly with data previously registered in a mouse model, we found that both dimeric species significantly decrease human melanoma A375 cell viability, while only N-dimers reduce human melanoma MeWo cell growth. Full article
(This article belongs to the Special Issue Current Approaches in Molecular Enzymology)
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Open AccessReview
Post-Infectious Guillain–Barré Syndrome Related to SARS-CoV-2 Infection: A Systematic Review
Life 2021, 11(2), 167; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020167 - 21 Feb 2021
Viewed by 560
Abstract
Background. Guillain-Barré syndrome (GBS) is the most common cause of flaccid paralysis, with about 100,000 people developing the disorder every year worldwide. Recently, the incidence of GBS has increased during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemics. We reviewed the literature to [...] Read more.
Background. Guillain-Barré syndrome (GBS) is the most common cause of flaccid paralysis, with about 100,000 people developing the disorder every year worldwide. Recently, the incidence of GBS has increased during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemics. We reviewed the literature to give a comprehensive overview of the demographic characteristics, clinical features, diagnostic investigations, and outcome of SARS-CoV-2-related GBS patients. Methods. Embase, MEDLINE, Google Scholar, and Cochrane Central Trials Register were systematically searched on 24 September 2020 for studies reporting on GBS secondary to COVID-19. Results. We identified 63 articles; we included 32 studies in our review. A total of 41 GBS cases with a confirmed or probable COVID-19 infection were reported: 26 of them were single case reports and 6 case series. Published studies on SARS-CoV-2-related GBS typically report a classic sensorimotor type of GBS often with a demyelinating electrophysiological subtype. Miller Fisher syndrome was reported in a quarter of the cases. In 78.1% of the cases, the response to immunomodulating therapy is favourable. The disease course is frequently severe and about one-third of the patients with SARS-CoV-2-associated GBS requires mechanical ventilation and Intensive Care Unit (ICU) admission. Rarely the outcome is poor or even fatal (10.8% of the cases). Conclusion. Clinical presentation, course, response to treatment, and outcome are similar in SARS-CoV-2-associated GBS and GBS due to other triggers. Full article
(This article belongs to the Special Issue Ecology, Evolution and Epidemiology of Coronaviruses)
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Open AccessArticle
Status of Nutrition in Hemodialysis Patients Survey (SNIPS): Nutrition Intake in Obese and Overweight vs. Healthy Weight Patients
Life 2021, 11(2), 166; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020166 - 21 Feb 2021
Viewed by 452
Abstract
Elevated body mass index (BMI) has been associated with improved survival and fewer hospitalizations in hemodialysis patients; however, it is not clear that dietary intake is associated with increased BMI in hemodialysis patients. The present analysis was designed to compare energy and macronutrient [...] Read more.
Elevated body mass index (BMI) has been associated with improved survival and fewer hospitalizations in hemodialysis patients; however, it is not clear that dietary intake is associated with increased BMI in hemodialysis patients. The present analysis was designed to compare energy and macronutrient intake and distribution, as well as compliance with the International Society of Renal Nutrition and Metabolism (ISRNM) dietary guidelines, by body weight status (overweight/obese vs. normal weight) in hemodialysis patients. The status of nutrition in hemodialysis patients survey (SNIPS) cohort is a cross-sectional study including a representative sample of individuals on hemodialysis treated in hospital dialysis centers throughout Israel. Of the 375 patients eligible for the current analysis, 60.1% had BMI ≥ 25 kg/m2 (overweight/obese). For each participant, the following measures were recorded: dietary intake, blood biochemistry, anthropometric and hemodynamic measures. These were compared by body weight status. Compared to their normal-weight counterparts, overweight/obese hemodialysis patients did not differ by energy and macronutrient intake, distribution of these nutrients in the diet. Regardless of body weight status, hemodialysis patients have poor compliance with ISRNM dietary guidelines. Full article
(This article belongs to the Special Issue Research Updates in Chronic Kidney Disease)
Open AccessReview
Disturbance of Mitochondrial Dynamics and Mitochondrial Therapies in Atherosclerosis
Life 2021, 11(2), 165; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020165 - 20 Feb 2021
Viewed by 578
Abstract
Mitochondrial dysfunction is associated with a wide range of chronic human disorders, including atherosclerosis and diabetes mellitus. Mitochondria are dynamic organelles that undergo constant turnover in living cells. Through the processes of mitochondrial fission and fusion, a functional population of mitochondria is maintained, [...] Read more.
Mitochondrial dysfunction is associated with a wide range of chronic human disorders, including atherosclerosis and diabetes mellitus. Mitochondria are dynamic organelles that undergo constant turnover in living cells. Through the processes of mitochondrial fission and fusion, a functional population of mitochondria is maintained, that responds to the energy needs of the cell. Damaged or excessive mitochondria are degraded by mitophagy, a specialized type of autophagy. These processes are orchestrated by a number of proteins and genes, and are tightly regulated. When one or several of these processes are affected, it can lead to the accumulation of dysfunctional mitochondria, deficient energy production, increased oxidative stress and cell death—features that are described in many human disorders. While severe mitochondrial dysfunction is known to cause specific and mitochondrial disorders in humans, progressing damage of the mitochondria is also observed in a wide range of other chronic diseases, including cancer and atherosclerosis, and appears to play an important role in disease development. Therefore, correction of mitochondrial dynamics can help in developing new therapies for the treatment of these conditions. In this review, we summarize the recent knowledge on the processes of mitochondrial turnover and the proteins and genes involved in it. We provide a list of known mutations that affect mitochondrial function, and discuss the emerging therapeutic approaches. Full article
(This article belongs to the Section Physiology and Pathology)
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Open AccessArticle
Spatio-Temporal Expression Pattern of Ki-67, pRB, MMP-9 and Bax in Human Secondary Palate Development
Life 2021, 11(2), 164; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020164 - 20 Feb 2021
Viewed by 377
Abstract
We analyzed the immunohistochemical expression of Ki-67, pRb, Bax, and MMP-9 during the human secondary palate formation (7th to 12th developmental weeks (DWs). The most significant proliferation was observed in the seventh DW with 32% of Ki-67-positive cells in the epithelium, while loose [...] Read more.
We analyzed the immunohistochemical expression of Ki-67, pRb, Bax, and MMP-9 during the human secondary palate formation (7th to 12th developmental weeks (DWs). The most significant proliferation was observed in the seventh DW with 32% of Ki-67-positive cells in the epithelium, while loose ectomesenchyme condensations (lec) and loose non-condensing ectomesenchyme (lnc) had only 18 and 11%, respectively (Kruskal–Wallis, p < 0.001), and diminished afterwards. Contrarily, pRb-positive cells were mostly located in the lnc (67%), with significant difference in comparison to epithelium and lec in all investigated periods (Kruskal–Wallis, p < 0.001). Ki-67- and pRb-positive cells co-expressed occasionally in all investigated periods. MMP-9 displayed a strong expression pattern with the highest number of positive cells during the seventh DW in the epithelium, with significant difference in comparison to lec and lnc (Kruskal–Wallis, p < 0.0001). The ninth DW is particularly important for the Bax expression, especially in the epithelium (84%), in comparison to lec (58%) and lnc (47%) (Kruskal–Wallis, p < 0.001). The co-expression of Bax and MMP-9 was seen only in the epithelium during seventh and ninth DWs. Our study indicates the parallel persistence of proliferation (Ki-67, pRb) and remodeling (MMP-9) that enables growth and apoptotic activity (Bax) that enable the removal of the epithelial cells at the fusion point during secondary palate formation. Full article
(This article belongs to the Special Issue 2020: A 10 Years Journey—Advances in Life Sciences)
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Open AccessArticle
Transcriptome Analysis of the Anti-TGFβ Effect of Schisandra chinensis Fruit Extract and Schisandrin B in A7r5 Vascular Smooth Muscle Cells
Life 2021, 11(2), 163; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020163 - 20 Feb 2021
Viewed by 433
Abstract
Schisandra chinensis fruit extract (SCE) has been used as a traditional medicine for treating vascular diseases. However, little is known about how SCE and schisandrin B (SchB) affect transcriptional output-a crucial factor for shaping the fibrotic responses of the transforming growth factor β [...] Read more.
Schisandra chinensis fruit extract (SCE) has been used as a traditional medicine for treating vascular diseases. However, little is known about how SCE and schisandrin B (SchB) affect transcriptional output-a crucial factor for shaping the fibrotic responses of the transforming growth factor β (TGFβ) signaling pathways in in vascular smooth muscle cells (VSMC). In this study, to assess the pharmacological effect of SCE and SchB on TGFβ-induced transcriptional output, we performed DNA microarray experiments in A7r5 VSMCs. We found that TGFβ induced distinctive changes in the gene expression profile and that these changes were considerably reversed by SCE and SchB. Gene Set Enrichment Analysis (GSEA) with Hallmark signature suggested that SCE or SchB inhibits a range of fibrosis-associated biological processes, including inflammation, cell proliferation and migration. With our VSMC-specific transcriptional interactome network, master regulator analysis identified crucial transcription factors that regulate the expression of SCE- and SchB-effective genes (i.e., TGFβ-reactive genes whose expression are reversed by SCE and SchB). Our results provide novel perspective and insight into understanding the pharmacological action of SCE and SchB at the transcriptome level and will support further investigations to develop multitargeted strategies for the treatment of vascular fibrosis. Full article
(This article belongs to the Special Issue Vascular Smooth Muscle Cell (VSMC) Differentiation)
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Open AccessArticle
Effect of 7-Methylsulfinylheptyl Isothiocyanate on the Inhibition of Melanogenesis in B16-F1 Cells
Life 2021, 11(2), 162; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020162 - 20 Feb 2021
Viewed by 380
Abstract
Skin aging, characterized by hyperpigmentation, inflammation, wrinkles, and skin cancer, is influenced by intrinsic and extrinsic factors with synergistic effects. Autophagy maintains the homeostatic balance between the degradation, synthesis, and recycling of cellular proteins and organelles, and plays important roles in several cellular [...] Read more.
Skin aging, characterized by hyperpigmentation, inflammation, wrinkles, and skin cancer, is influenced by intrinsic and extrinsic factors with synergistic effects. Autophagy maintains the homeostatic balance between the degradation, synthesis, and recycling of cellular proteins and organelles, and plays important roles in several cellular and biological processes, including aging. The compound 7-methylsulfinylheptyl isothiocyanate (7-MSI) is a sulfur-containing phytochemical produced by various plants, particularly cruciferous vegetables, with reported anti-inflammatory properties and a role in pathogen defense; however, its effects on skin whitening have not been studied in detail. The purpose of this study was to observe the effects of 7-MSI on skin whitening and autophagy in cultured murine melanoma (B16-F1) cells. Western blotting was used to evaluate the impact of 7-MSI on melanogenesis-, tyrosinase-, and autophagy-associated proteins. The levels of the melanogenesis-associated protein’s microphthalmia-associated transcription factor (MITF) and tyrosinase and tyrosinase-related protein-1 were decreased by treatment with 7-MSI under melanogenesis induction. Melanin synthesis also decreased by approximately 63% after treatment with 7-MSI for 73 h, compared with that non-treated controls. In addition, autophagosome formation and the expression levels of the autophagy-related proteins mTOR, p-mTOR, Beclin-1, Atg12, and LC3 were higher in 7-MSI-treated B16-F1 cells than in non-treated cells. These results indicate that 7-MSI can inhibit melanin synthesis in B16-F1 cells by suppressing melanogenesis and autophagy activation and thus can potentially be used as a novel multifunctional cosmetic agent. Full article
(This article belongs to the Section Cell Biology and Tissue Engineering)
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Open AccessArticle
Revisiting the Instrumented Romberg Test: Can Today’s Technology Offer a Risk-of-Fall Screening Device for Senior Citizens? An Experience-Based Approach
Life 2021, 11(2), 161; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020161 - 20 Feb 2021
Viewed by 410
Abstract
Risk of fall (ROF) is a worldwide major concern for its prevalence and consequent dramatic outcomes in the elderly population. The growing age-related risk appears to be associated with increasing motor, sensory, and cognitive problems in the elderly population. There is a consensus [...] Read more.
Risk of fall (ROF) is a worldwide major concern for its prevalence and consequent dramatic outcomes in the elderly population. The growing age-related risk appears to be associated with increasing motor, sensory, and cognitive problems in the elderly population. There is a consensus on the need to screen for these balance dysfunctions, but the available methods are largely based on subjectively assessed performances. The instrumented Romberg test using a force plate represents a validated assessment process for the evaluation of balance performances. The purpose of this study is to propose an innovative instrumental method to identify balance deficits, assess their severity, and give an automated indication of the most likely etiology. The proposed new method was applied to the instrumented Romberg test, using force plate data recorded in a cohort of 551 females aged >65 participating in adapted physical activity courses. The method allowed us to identify 145 dysfunctional subjects and to determine the likely origin of their deficit: 21 central, 5 vestibular, 9 visual, 59 proprioceptive (musculoskeletal etiology), and 51 functional. Based on the preliminary findings of the study, this test could be an efficient and cost-effective mass screening tool for identifying subjects at risk of fall, since the procedure proves to be rapid, non-invasive, and apparently devoid of any contraindications. Full article
(This article belongs to the Section Medical Research)
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Open AccessArticle
Mechanisms of Cisplatin in Combination with Repurposed Drugs against Human Endometrial Carcinoma Cells
Life 2021, 11(2), 160; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020160 - 19 Feb 2021
Viewed by 459
Abstract
Although endometrial carcinoma is one of the most common gynecological malignancies worldwide, its precise etiology remains unknown. Moreover, no novel adjuvant and/or targeted therapies are currently being developed to achieve greater efficacy for endometrial cancer patients who develop chemotherapeutic drug resistance. In this [...] Read more.
Although endometrial carcinoma is one of the most common gynecological malignancies worldwide, its precise etiology remains unknown. Moreover, no novel adjuvant and/or targeted therapies are currently being developed to achieve greater efficacy for endometrial cancer patients who develop chemotherapeutic drug resistance. In this study, we used three human endometrial cancer cell lines, RL95-2, HEC-1-A, and KLE, to investigate the responsiveness of cisplatin alone and in combination with potential repurposed drugs. We first found that RL95-2 cells were more sensitive to cisplatin than HEC-1-A or KLE cells. The cytotoxicity of cisplatin in RL95-2 cells may reflect its ability to perturb the cell cycle, reactive oxygen species production and autophagy as well as to induce senescence and DNA damage. Similar effects, although not DNA damage, were also observed in HEC-1-A and KLE cells. In addition, downregulation of p53 and/or cyclin D1 may also impact the responsiveness of HEC-1-A and KLE cells to cisplatin. We also observed that resveratrol, trichostatin A (TSA), caffeine, or digoxin increased the apoptotic process of cisplatin toward RL95-2 cells, while amiodarone or TSA increased its apoptotic process toward HEC-1-A cells. The combination index supported the assertion that the combination of cisplatin with caffeine, amiodarone, resveratrol, metformin, digoxin, or TSA increases the cytotoxicity of cisplatin in HEC-1-A cells. These findings suggest potential strategies for enhancing the efficacy of cisplatin to overcome drug resistance in endometrial carcinoma patients. Full article
(This article belongs to the Section Pharmaceutical Science)
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Open AccessEditorial
Exercise Biomechanics and Physiology
Life 2021, 11(2), 159; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020159 - 19 Feb 2021
Viewed by 332
Abstract
Biomechanics was defined by Hatze in 1974 as the study of the movement of living things using the science of mechanics [...] Full article
(This article belongs to the Special Issue Exercise Biomechanics and Physiology)
Open AccessReview
A Novel 89Zr-labeled DDS Device Utilizing Human IgG Variant (scFv): “Lactosome” Nanoparticle-Based Theranostics for PET Imaging and Targeted Therapy
Life 2021, 11(2), 158; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020158 - 18 Feb 2021
Cited by 1 | Viewed by 648
Abstract
“Theranostics,” a new concept of medical advances featuring a fusion of therapeutic and diagnostic systems, provides promising prospects in personalized medicine, especially cancer. The theranostics system comprises a novel 89Zr-labeled drug delivery system (DDS), derived from the novel biodegradable polymeric micelle, “Lactosome” [...] Read more.
“Theranostics,” a new concept of medical advances featuring a fusion of therapeutic and diagnostic systems, provides promising prospects in personalized medicine, especially cancer. The theranostics system comprises a novel 89Zr-labeled drug delivery system (DDS), derived from the novel biodegradable polymeric micelle, “Lactosome” nanoparticles conjugated with specific shortened IgG variant, and aims to successfully deliver therapeutically effective molecules, such as the apoptosis-inducing small interfering RNA (siRNA) intracellularly while offering simultaneous tumor visualization via PET imaging. A 27 kDa-human single chain variable fragment (scFv) of IgG to establish clinically applicable PET imaging and theranostics in cancer medicine was fabricated to target mesothelin (MSLN), a 40 kDa-differentiation-related cell surface glycoprotein antigen, which is frequently and highly expressed by malignant tumors. This system coupled with the cell penetrating peptide (CPP)-modified and photosensitizer (e.g., 5, 10, 15, 20-tetrakis (4-aminophenyl) porphyrin (TPP))-loaded Lactosome particles for photochemical internalized (PCI) driven intracellular siRNA delivery and the combination of 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) offers a promising nano-theranostic-based cancer therapy via its targeted apoptosis-inducing feature. This review focuses on the combined advances in nanotechnology and material sciences utilizing the “89Zr-labeled CPP and TPP-loaded Lactosome particles” and future directions based on important milestones and recent developments in this platform. Full article
(This article belongs to the Special Issue Theranostics: Current and Future Perspectives)
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Open AccessArticle
Preliminary Evaluation of Protective Efficacy of Inactivated Senecavirus A on Pigs
Life 2021, 11(2), 157; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020157 - 18 Feb 2021
Viewed by 373
Abstract
Senecavirus A (SVA), formerly known as Seneca Valley virus (SVV), causes vesicular symptoms in adult pigs and acute death of neonatal piglets. This pathogen has emerged in major swine producing countries around the world and caused significant economic losses to the pig industry. [...] Read more.
Senecavirus A (SVA), formerly known as Seneca Valley virus (SVV), causes vesicular symptoms in adult pigs and acute death of neonatal piglets. This pathogen has emerged in major swine producing countries around the world and caused significant economic losses to the pig industry. Thus, it is necessary to develop strategies to prevent and control SVA infection. Herein, an SVA strain (named GD-ZYY02-2018) was isolated from a pig herd with vesicular symptoms in Guangdong province of China in 2018. The present study aimed to carry out the phylogenetic analysis of the GD-ZYY02-2018 strain, determine its pathogenicity in finishing pigs, and assess the protective efficacy of the inactivated GD-ZYY02-2018 strain against virus challenge. The results of phylogenetic analysis showed that the SVA GD-ZYY02-2018 strain belonged to the USA-like strains and had a close genetic relationship with recent Chinese SVA strains. Animal challenge experiment showed that 100-day-old pigs inoculated intranasally with SVA GD-ZYY02-2018 strain developed vesicular lesion, low fever, viremia, and virus shedding in feces. The immunization challenge experiment showed that pigs vaccinated with inactivated GD-ZYY02-2018 strain could produce a high titer of anti-SVA neutralizing antibody and no vesicular lesion, fever, viremia, and virus shedding in feces was observed in vaccinated pigs after challenge with GD-ZYY02-2018 strain, indicating that inactivated GD-ZYY02-2018 could protect finishing pigs against the challenge of homologous virus. In conclusion, preliminary results indicated that inactivated GD-ZYY02-2018 could be used as a candidate vaccine for in-depth research and might be conducive to the prevention and control of SVA infection. Full article
(This article belongs to the Section Animal Science)
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Open AccessArticle
Titanium and Platinum–Fluoroplastic Stapes Prostheses Visualization on Cone Beam Computed Tomography and High-Resolution Computed Tomography
Life 2021, 11(2), 156; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020156 - 17 Feb 2021
Viewed by 434
Abstract
Objective: The aim of this study was to evaluate whether stapes prostheses can be visualized with less metal artifacts and therefore more accurately on cone beam computed tomography in comparison to computed tomography imaging. Recent studies have shown that cone beam computed tomography [...] Read more.
Objective: The aim of this study was to evaluate whether stapes prostheses can be visualized with less metal artifacts and therefore more accurately on cone beam computed tomography in comparison to computed tomography imaging. Recent studies have shown that cone beam computed tomography has advantages when imaging metal artifacts. Patients with hearing loss or vertigo, who have undergone stapedotomy, often present a challenge for otologic surgeons. Imaging studies can deliver crucial additional information. Methods: A retrospective analysis of imaging studies and clinical data in a tertiary care center were carried out. Forty-one patients with forty-five implanted ears were evaluated in the study. All included patients had been implanted with a platinum–fluoroplastic (n = 19) or titanium (n = 26) piston and subsequently had undergone imaging months or years after surgery for various reasons. Patients underwent computed tomography or cone beam computed tomography of the temporal bone depending on availability. Piston visualization, prosthesis length, vestibular intrusion and audiologic results were compared between the groups. Piston position on imaging studies were compared to intraoperative findings. Results: Functional length measurements of all prostheses were carried out with a mean error of −0.17 mm (±0.20). Platinum–fluoroplastic protheses were significantly underestimated in length compared to titanium prostheses. To analyze the material-dependent difference in the measurement errors of the imaging techniques the interaction was tested in an ANOVA model and showed no statistically significant result (p = 0.24). The blinded neuroradiologist viewed two implants, both platinum–fluoroplastic pistons, as located outside of the vestibule due to an underestimation of the prothesis length and the missing radiodensity of the lower end of the prosthesis. Conclusion: Surgeons and radiologists should be aware of the different types and radiologic features of stapes prostheses and the missing radiodensity of some protheses parts. Cone beam computed tomography is an imaging alternative with a potential advantage of reduced radiation in patients after stapes surgery suffering from vertigo or hearing loss to evaluate piston position. Full article
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Open AccessArticle
Therapeutic Potentials of Syzygium fruticosum Fruit (Seed) Reflected into an Array of Pharmacological Assays and Prospective Receptors-Mediated Pathways
Life 2021, 11(2), 155; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020155 - 17 Feb 2021
Viewed by 603
Abstract
Syzygium fruticosum (SF), a valuable Bangladeshi fruit, is considered an alternative therapeutic agent. Mainly, seeds are used as nutritional phytotherapy to ease physical and mental status by preventing chronic diseases. Here, we scrutinized the S. fruticosum seed’s fundamental importance in traditional medicine by [...] Read more.
Syzygium fruticosum (SF), a valuable Bangladeshi fruit, is considered an alternative therapeutic agent. Mainly, seeds are used as nutritional phytotherapy to ease physical and mental status by preventing chronic diseases. Here, we scrutinized the S. fruticosum seed’s fundamental importance in traditional medicine by following an integrated approach combining in vivo, in vitro, and in silico studies. The SF was fractionated with different solvents, and the ethyl acetate fraction of SF (EaF-SF) was further studied. Mice treated with EaF-SF (200 and 400 mg/kg) manifested anxiolysis evidenced by higher exploration in elevated plus maze and hole board tests. Similarly, a dose-dependent drop of immobility time in a forced swimming test ensured significant anti-depressant activity. Moreover, higher dose treatment exposed reduced exploratory behaviour resembling decreased movement and prolonged sleeping latency with a quick onset of sleep during the open field and thiopental-induced sleeping tests, respectively. In parallel, EaF-SF significantly (p < 0.001) and dose-dependently suppressed acetic acid and formalin-induced pain in mice. Also, a noteworthy anti-inflammatory activity and a substantial (p < 0.01) clot lysis activity (thrombolytic) was observed. Gas chromatography-mass spectrometry (GC–MS) analysis resulted in 49 bioactive compounds. Among them, 12 bioactive compounds with Lipinski’s rule and safety confirmation showed strong binding affinity (molecular docking) against the receptors of each model used. To conclude, the S. fruticosum seed is a prospective source of health-promoting effects that can be an excellent candidate for preventing degenerative diseases. Full article
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Open AccessReview
Origin of Species before Origin of Life: The Role of Speciation in Chemical Evolution
Life 2021, 11(2), 154; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020154 - 17 Feb 2021
Viewed by 1137
Abstract
Speciation, an evolutionary process by which new species form, is ultimately responsible for the incredible biodiversity that we observe on Earth every day. Such biodiversity is one of the critical features which contributes to the survivability of biospheres and modern life. While speciation [...] Read more.
Speciation, an evolutionary process by which new species form, is ultimately responsible for the incredible biodiversity that we observe on Earth every day. Such biodiversity is one of the critical features which contributes to the survivability of biospheres and modern life. While speciation and biodiversity have been amply studied in organismic evolution and modern life, it has not yet been applied to a great extent to understanding the evolutionary dynamics of primitive life. In particular, one unanswered question is at what point in the history of life did speciation as a phenomenon emerge in the first place. Here, we discuss the mechanisms by which speciation could have occurred before the origins of life in the context of chemical evolution. Specifically, we discuss that primitive compartments formed before the emergence of the last universal common ancestor (LUCA) could have provided a mechanism by which primitive chemical systems underwent speciation. In particular, we introduce a variety of primitive compartment structures, and associated functions, that may have plausibly been present on early Earth, followed by examples of both discriminate and indiscriminate speciation affected by primitive modes of compartmentalization. Finally, we discuss modern technologies, in particular, droplet microfluidics, that can be applied to studying speciation phenomena in the laboratory over short timescales. We hope that this discussion highlights the current areas of need in further studies on primitive speciation phenomena while simultaneously proposing directions as important areas of study to the origins of life. Full article
(This article belongs to the Special Issue From Messy Chemistry to the Origin of Life)
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Open AccessReview
Evidence of the Cellular Senescence Stress Response in Mitotically Active Brain Cells—Implications for Cancer and Neurodegeneration
Life 2021, 11(2), 153; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020153 - 17 Feb 2021
Cited by 1 | Viewed by 740
Abstract
Cellular stress responses influence cell fate decisions. Apoptosis and proliferation represent opposing reactions to cellular stress or damage and may influence distinct health outcomes. Clinical and epidemiological studies consistently report inverse comorbidities between age-associated neurodegenerative diseases and cancer. This review discusses how one [...] Read more.
Cellular stress responses influence cell fate decisions. Apoptosis and proliferation represent opposing reactions to cellular stress or damage and may influence distinct health outcomes. Clinical and epidemiological studies consistently report inverse comorbidities between age-associated neurodegenerative diseases and cancer. This review discusses how one particular stress response, cellular senescence, may contribute to this inverse correlation. In mitotically competent cells, senescence is favorable over uncontrolled proliferation, i.e., cancer. However, senescent cells notoriously secrete deleterious molecules that drive disease, dysfunction and degeneration in surrounding tissue. In recent years, senescent cells have emerged as unexpected mediators of neurodegenerative diseases. The present review uses pre-defined criteria to evaluate evidence of cellular senescence in mitotically competent brain cells, highlights the discovery of novel molecular regulators and discusses how this single cell fate decision impacts cancer and degeneration in the brain. We also underscore methodological considerations required to appropriately evaluate the cellular senescence stress response in the brain. Full article
(This article belongs to the Special Issue Cellular Senescence in Health, Disease and Aging: Blessing or Curse?)
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Open AccessReview
Housekeeping in the Hydrosphere: Microbial Cooking, Cleaning, and Control under Stress
Life 2021, 11(2), 152; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020152 - 17 Feb 2021
Viewed by 1180
Abstract
Who’s cooking, who’s cleaning, and who’s got the remote control within the waters blanketing Earth? Anatomically tiny, numerically dominant microbes are the crucial “homemakers” of the watery household. Phytoplankton’s culinary abilities enable them to create food by absorbing sunlight to fix carbon and [...] Read more.
Who’s cooking, who’s cleaning, and who’s got the remote control within the waters blanketing Earth? Anatomically tiny, numerically dominant microbes are the crucial “homemakers” of the watery household. Phytoplankton’s culinary abilities enable them to create food by absorbing sunlight to fix carbon and release oxygen, making microbial autotrophs top-chefs in the aquatic kitchen. However, they are not the only bioengineers that balance this complex household. Ubiquitous heterotrophic microbes including prokaryotic bacteria and archaea (both “bacteria” henceforth), eukaryotic protists, and viruses, recycle organic matter and make inorganic nutrients available to primary producers. Grazing protists compete with viruses for bacterial biomass, whereas mixotrophic protists produce new organic matter as well as consume microbial biomass. When viruses press remote-control buttons, by modifying host genomes or lysing them, the outcome can reverberate throughout the microbial community and beyond. Despite recognition of the vital role of microbes in biosphere housekeeping, impacts of anthropogenic stressors and climate change on their biodiversity, evolution, and ecological function remain poorly understood. How trillions of the smallest organisms in Earth’s largest ecosystem respond will be hugely consequential. By making the study of ecology personal, the “housekeeping” perspective can provide better insights into changing ecosystem structure and function at all scales. Full article
(This article belongs to the Section Ecology)
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Open AccessArticle
Multidrug-Resistant Acinetobacter baumannii Genetic Characterization and Spread in Lithuania in 2014, 2016, and 2018
Life 2021, 11(2), 151; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020151 - 16 Feb 2021
Viewed by 466
Abstract
Bacterial resistance to antimicrobial agents plays an important role in the treatment of bacterial infections in healthcare institutions. The spread of multidrug-resistant bacteria can occur during inter- and intra-hospital transmissions among patients and hospital personnel. For this reason, more studies must be conducted [...] Read more.
Bacterial resistance to antimicrobial agents plays an important role in the treatment of bacterial infections in healthcare institutions. The spread of multidrug-resistant bacteria can occur during inter- and intra-hospital transmissions among patients and hospital personnel. For this reason, more studies must be conducted to understand how resistance occurs in bacteria and how it moves between hospitals by comparing data from different years and looking out for any patterns that might emerge. Multidrug-resistant (MDR) Acinetobacter spp. was studied at 14 healthcare institutions in Lithuania during 2014, 2016, and 2018 using samples from human bloodstream infections. In total, 194 isolates were collected and identified using MALDI-TOF and VITEK2 analyzers as Acinetobacter baumannii group bacteria. After that, the isolates were analyzed for the presence of different resistance genes (20 genes were analyzed) and characterized by using the Rep-PCR and MLVA (multiple-locus variable-number tandem repeat analysis) genotyping methods. The results of the study showed the relatedness of the different Acinetobacter spp. isolates and a possible circulation of resistance genes or profiles during the different years of the study. This study provides essential information, such as variability and diversity of resistance genes, genetic profiling, and clustering of isolates, to better understand the antimicrobial resistance patterns of Acinetobacter spp. These results can be used to strengthen the control of multidrug-resistant infections in healthcare institutions and to prevent potential outbreaks of this pathogen in the future. Full article
(This article belongs to the Special Issue Antimicrobial Resistance)
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Open AccessReview
Structures and Divergent Mechanisms in Capsid Maturation and Stabilization Following Genome Packaging of Human Cytomegalovirus and Herpesviruses
Life 2021, 11(2), 150; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020150 - 16 Feb 2021
Viewed by 708
Abstract
Herpesviruses are the causative agents of several diseases. Infections are generally mild or asymptomatic in immunocompetent individuals. In contrast, herpesvirus infections continue to contribute to significant morbidity and mortality in immunocompromised patients. Few drugs are available for the treatment of human herpesvirus infections, [...] Read more.
Herpesviruses are the causative agents of several diseases. Infections are generally mild or asymptomatic in immunocompetent individuals. In contrast, herpesvirus infections continue to contribute to significant morbidity and mortality in immunocompromised patients. Few drugs are available for the treatment of human herpesvirus infections, mainly targeting the viral DNA polymerase. Moreover, no successful therapeutic options are available for the Epstein–Barr virus or human herpesvirus 8. Most licensed drugs share the same mechanism of action of targeting the viral polymerase and thus blocking DNA polymerization. Resistances to antiviral drugs have been observed for human cytomegalovirus, herpes simplex virus and varicella-zoster virus. A new terminase inhibitor, letermovir, recently proved effective against human cytomegalovirus. However, the letermovir has no significant activity against other herpesviruses. New antivirals targeting other replication steps, such as capsid maturation or DNA packaging, and inducing fewer adverse effects are therefore needed. Targeting capsid assembly or DNA packaging provides additional options for the development of new drugs. In this review, we summarize recent findings on capsid assembly and DNA packaging. We also described what is known about the structure and function of capsid and terminase proteins to identify novels targets for the development of new therapeutic options. Full article
(This article belongs to the Special Issue Capsid Protein)
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Open AccessCommunication
Formation of Thiophene under Simulated Volcanic Hydrothermal Conditions on Earth—Implications for Early Life on Extraterrestrial Planets?
Life 2021, 11(2), 149; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020149 - 16 Feb 2021
Viewed by 548
Abstract
Thiophene was detected on Mars during the Curiosity mission in 2018. The compound was even suggested as a biomarker due to its possible origin from diagenesis or pyrolysis of biological material. In the laboratory, thiophene can be synthesized at 400 °C by reacting [...] Read more.
Thiophene was detected on Mars during the Curiosity mission in 2018. The compound was even suggested as a biomarker due to its possible origin from diagenesis or pyrolysis of biological material. In the laboratory, thiophene can be synthesized at 400 °C by reacting acetylene and hydrogen sulfide on alumina. We here show that thiophene and thiophene derivatives are also formed abiotically from acetylene and transition metal sulfides such as NiS, CoS and FeS under simulated volcanic, hydrothermal conditions on Early Earth. Exactly the same conditions were reported earlier to have yielded a plethora of organic molecules including fatty acids and other components of extant metabolism. It is therefore tempting to suggest that thiophenes from abiotic formation could indicate sites and conditions well-suited for the evolution of metabolism and potentially for the origin-of-life on extraterrestrial planets. Full article
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Open AccessReview
When a Neonate Is Born, So Is a Microbiota
Life 2021, 11(2), 148; https://0-doi-org.brum.beds.ac.uk/10.3390/life11020148 - 16 Feb 2021
Viewed by 476
Abstract
In recent years, the role of human microbiota as a short- and long-term health promoter and modulator has been affirmed and progressively strengthened. In the course of one’s life, each subject is colonized by a great number of bacteria, which constitute its specific [...] Read more.
In recent years, the role of human microbiota as a short- and long-term health promoter and modulator has been affirmed and progressively strengthened. In the course of one’s life, each subject is colonized by a great number of bacteria, which constitute its specific and individual microbiota. Human bacterial colonization starts during fetal life, in opposition to the previous paradigm of the “sterile womb”. Placenta, amniotic fluid, cord blood and fetal tissues each have their own specific microbiota, influenced by maternal health and habits and having a decisive influence on pregnancy outcome and offspring outcome. The maternal microbiota, especially that colonizing the genital system, starts to influence the outcome of pregnancy already before conception, modulating fertility and the success rate of fertilization, even in the case of assisted reproduction techniques. During the perinatal period, neonatal microbiota seems influenced by delivery mode, drug administration and many other conditions. Special attention must be reserved for early neonatal nutrition, because breastfeeding allows the transmission of a specific and unique lactobiome able to modulate and positively affect the neonatal gut microbiota. Our narrative review aims to investigate the currently identified pre- and peri-natal factors influencing neonatal microbiota, before conception, during pregnancy, pre- and post-delivery, since the early microbiota influences the whole life of each subject. Full article
(This article belongs to the Special Issue Pediatric Nutrition for a Healthy Life)
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