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Life, Volume 10, Issue 11 (November 2020) – 57 articles

Cover Story (view full-size image): Type IV pili (T4P) are cell-surface proteinaceous filaments found in many prokaryotic organisms and convey twitching motility through their extension/retraction cycles, moving cells across surfaces. In cyanobacteria, twitching motility is the sole mode of motility characterised to date and is how cells perform phototaxis, the movement towards and away from directional light sources. Wavelength and intensity of light determine the direction of movement and signal for some cyanobacteria to form multicellular assemblages. Formation of such aggregates allows for acclimation to unfavourable environmental conditions and stresses. T4P also enable natural transformation and secretion processes. Thus, cyanobacteria respond to external stimuli by escaping unfavourable environmental conditions via phototaxis, exchanging genetic material, or modifying their surroundings to better fit their needs. [...] Read more.
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Article
Prognostic Role of FGFR3 Expression Status and Tumor-Related MicroRNAs Level in Association with PD-L1 Expression in Primary Luminal Non-Muscular Invasive Bladder Carcinoma
Life 2020, 10(11), 305; https://doi.org/10.3390/life10110305 - 23 Nov 2020
Cited by 1 | Viewed by 730
Abstract
Background: bladder cancer is one of the most common urinary tract malignancies. Establishment of robust predictors of disease progression and outcome is important for personalizing treatment of non-muscular invasive bladder carcinoma (NMIBC). In this study we evaluated association of PD-L1 expression with other [...] Read more.
Background: bladder cancer is one of the most common urinary tract malignancies. Establishment of robust predictors of disease progression and outcome is important for personalizing treatment of non-muscular invasive bladder carcinoma (NMIBC). In this study we evaluated association of PD-L1 expression with other prognostic biomarkers, such as expression of miRNA-145 and miRNA-200a, FGFR3 gene expression, and mutation status in tissue specimens of the luminal subtype of newly diagnosed high and low grade NMIBC. Methods: twenty patients with primary luminal NMIBC were enrolled in the study. Tumor grade and risk level were determined in accordance with European Organization for Research and Treatment of Cancer (EORTC) guidelines and World Health Organization (WHO) classification. Neoplasm molecular subtype and PD-L1 expression level were assessed by immunohistochemistry. We used real-time PCR to evaluate the expression of microRNAs and FGFR3. We detected FGFR3 hotspot mutations in codons 248 and 249 by Sanger sequencing. Results: high grade primary luminal NMIBC showed comparatively higher expression of PD-L1 and microRNA-145 than a low grade tumor, whereas the latter had a higher FGFR3 expression and hotspot mutation rate. The tumor grade (HR = 571.72 [11.03–2.96] p = 0.002), PD-L1 expression (HR = 2.33 [0.92–1.92] p = 0.012), and FGFR3 expression (HR = 0.08 [0.17–0.42] p = 0.003) were associated with relapse-free survival. Conclusions: tumor grade in association with PD-L1 and FGFR3 expression can be considered as a complex predictor for primary luminal NMIBC progression. Full article
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Review
Human Mitochondrial Pathologies of the Respiratory Chain and ATP Synthase: Contributions from Studies of Saccharomyces cerevisiae
Life 2020, 10(11), 304; https://doi.org/10.3390/life10110304 - 23 Nov 2020
Cited by 1 | Viewed by 842
Abstract
The ease with which the unicellular yeast Saccharomyces cerevisiae can be manipulated genetically and biochemically has established this organism as a good model for the study of human mitochondrial diseases. The combined use of biochemical and molecular genetic tools has been instrumental in [...] Read more.
The ease with which the unicellular yeast Saccharomyces cerevisiae can be manipulated genetically and biochemically has established this organism as a good model for the study of human mitochondrial diseases. The combined use of biochemical and molecular genetic tools has been instrumental in elucidating the functions of numerous yeast nuclear gene products with human homologs that affect a large number of metabolic and biological processes, including those housed in mitochondria. These include structural and catalytic subunits of enzymes and protein factors that impinge on the biogenesis of the respiratory chain. This article will review what is currently known about the genetics and clinical phenotypes of mitochondrial diseases of the respiratory chain and ATP synthase, with special emphasis on the contribution of information gained from pet mutants with mutations in nuclear genes that impair mitochondrial respiration. Our intent is to provide the yeast mitochondrial specialist with basic knowledge of human mitochondrial pathologies and the human specialist with information on how genes that directly and indirectly affect respiration were identified and characterized in yeast. Full article
(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)
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Article
Effect of Acetaminophen (APAP) on Physiological Indicators in Lactuca sativa
Life 2020, 10(11), 303; https://doi.org/10.3390/life10110303 - 23 Nov 2020
Cited by 1 | Viewed by 763
Abstract
This study analyzes the effects of acetaminophen (APAP) as a contaminant on physiological characteristics of lettuce plants (Lactuca sativa L.). Experiments were provided in an experimental greenhouse with semi-controlled conditions. The effect of different amounts of contaminant was evaluated by using regression [...] Read more.
This study analyzes the effects of acetaminophen (APAP) as a contaminant on physiological characteristics of lettuce plants (Lactuca sativa L.). Experiments were provided in an experimental greenhouse with semi-controlled conditions. The effect of different amounts of contaminant was evaluated by using regression analysis. Plants were grown in five concentrations of APAP: 0 µM, 5 µM, 50 µM, 500 µM, and 5 mM for 14 days in two variants, acute and chronic. The obtained results show that the monitored parameters were demonstrably influenced by the experimental variant. Plants are more sensitive to chronic contamination compared to acute. Significant (p < 0.05) deviation in photosynthesis and fluorescence was observed compared to the control in different variants. The highest doses of APAP reduced the intensity of photosynthesis by a maximum of more than 31% compared to the control. A reduction of 18% was observed for the fluorescence parameters. Pronounced correlation was described between chlorophyll fluorescence parameters and yield mainly under APAP conditions. The amount of chlorophyll was influenced by exposure to APAP. Full article
(This article belongs to the Special Issue Metabolism of Photosynthetic Organisms)
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Case Report
Long-Term SARS-CoV-2 Infection Associated with Viral Dissemination in Different Body Fluids Including Bile in Two Patients with Acute Cholecystitis
Life 2020, 10(11), 302; https://doi.org/10.3390/life10110302 - 23 Nov 2020
Cited by 4 | Viewed by 649
Abstract
Our study aimed to investigate the kinetics of SARS-CoV-2 RNA in bile and in different body fluids of two SARS-CoV-2 positive patients with acute cholecystitis by innovative droplet digital PCR (ddPCR) assays. For each patient, nasopharyngeal- and rectal swabs, bile, urine, and plasma [...] Read more.
Our study aimed to investigate the kinetics of SARS-CoV-2 RNA in bile and in different body fluids of two SARS-CoV-2 positive patients with acute cholecystitis by innovative droplet digital PCR (ddPCR) assays. For each patient, nasopharyngeal- and rectal swabs, bile, urine, and plasma samples were collected at different time points for SARS-CoV-2 RNA quantification by two ddPCR assays. For both patients, ddPCR revealed persistent and prolonged detection of viral RNA in the nasopharyngeal swab despite triple-negative or single-positive results by qRT-PCR. In Patient 1, SARS-CoV-2 RNA dropped more rapidly in bile and rectal-swab and declined slowly in nasopharyngeal swab and plasma, becoming undetectable in all compartments 97 days after symptoms started. Conversely, in patient 2, SARS-CoV-2 RNA was detected, even if at low copies, in all body samples (with the exception of urine) up to 75 days after the onset of symptoms. This study highlights that SARS-CoV-2 RNA can persist for a prolonged time in respiratory samples and in several biological samples despite negativity to qRT-PCR, supporting SARS-CoV-2’s ability to provoke persistent and disseminated infection and therefore to contribute to extra-pulmonary clinical manifestations. Full article
(This article belongs to the Special Issue The New Challenges in Infectious Diseases)
Article
Red Blood Cell Distribution Width Is Associated with Deterioration of Renal Function and Cardiovascular Morbidity and Mortality in Patients with Diabetic Kidney Disease
Life 2020, 10(11), 301; https://doi.org/10.3390/life10110301 - 22 Nov 2020
Cited by 2 | Viewed by 654
Abstract
We sought to investigate the possible association between Red Blood Cell Distribution Width (RDW), vascular calcification, oxidative stress and renal function and all-cause/cardiovascular (CV) mortality, CV events and progression of kidney disease in a cohort of patients with Diabetic Kidney Disease (DKD). Carotid [...] Read more.
We sought to investigate the possible association between Red Blood Cell Distribution Width (RDW), vascular calcification, oxidative stress and renal function and all-cause/cardiovascular (CV) mortality, CV events and progression of kidney disease in a cohort of patients with Diabetic Kidney Disease (DKD). Carotid intima media thickness (cIMT) and oxidized low-density cholesterol were measured in 104 Type 2 Diabetes Mellitus (T2DM) patients with established DKD, distributed in all five stages of kidney disease and 38 diabetics with normal renal function. All patients were followed for 7 years with end-points all-cause and CV mortality, CV events and progression to End-Stage Renal Disease (ESRD). RDW was positively correlated with diabetes duration (r = 0.19, p = 0.023) and albuminuria (r = 0.29, p = 0.002). Multivariate regression analysis revealed that RDW was a strong, independent predictor of cIMT value (β = 0.031, p = 0.012). Kaplan-Meier curves and Cox proportional hazard models revealed that after adjustment for several cofounders, RDW was a significant and independent predictor for all-cause mortality, CV mortality, CV event and progression to ESRD (HR 1.75, p = 0.001, HR 2.03, p = 0.001, HR = 1.66, p < 0.0001 and HR 2.14, p = 0.001 respectively). RDW predicts mortality, CV events and deterioration of renal function in DKD, probably reflecting atherosclerosis. Full article
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Article
Regulatory Potential of Long Non-Coding RNAs (lncRNAs) in Boar Spermatozoa with Good and Poor Freezability
Life 2020, 10(11), 300; https://doi.org/10.3390/life10110300 - 21 Nov 2020
Viewed by 780
Abstract
Long non-coding RNAs (lncRNAs) are suggested to play an important role in the sperm biological processes. We performed de novo transcriptome assembly to characterize lncRNAs in spermatozoa, and to investigate the role of the potential target genes of the differentially expressed lncRNAs (DElncRNAs) [...] Read more.
Long non-coding RNAs (lncRNAs) are suggested to play an important role in the sperm biological processes. We performed de novo transcriptome assembly to characterize lncRNAs in spermatozoa, and to investigate the role of the potential target genes of the differentially expressed lncRNAs (DElncRNAs) in sperm freezability. We detected approximately 4007 DElncRNAs, which were differentially expressed in spermatozoa from boars classified as having good and poor semen freezability (GSF and PSF, respectively). Most of the DElncRNAs were upregulated in boars of the PSF group and appeared to significantly affect the sperm’s response to the cryopreservation conditions. Furthermore, we predicted that the potential target genes were regulated by DElncRNAs in cis or trans. It was found that DElncRNAs of both freezability groups had potential cis- and trans-regulatory effects on different protein-coding genes, such as COX7A2L, TXNDC8 and SOX-7. Gene Ontology (GO) enrichment revealed that the DElncRNA target genes are associated with numerous biological processes, including signal transduction, response to stress, cell death (apoptosis), motility and embryo development. Significant differences in the de novo assembled transcriptome expression profiles of the DElncRNAs between the freezability groups were confirmed by quantitative real-time PCR analysis. This study reveals the potential effects of protein-coding genes of DElncRNAs on sperm functions, which could contribute to further research on their relevance in semen freezability. Full article
(This article belongs to the Section Animal Science)
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Review
The Model System Saccharomyces cerevisiae Versus Emerging Non-Model Yeasts for the Production of Biofuels
Life 2020, 10(11), 299; https://doi.org/10.3390/life10110299 - 21 Nov 2020
Cited by 4 | Viewed by 806
Abstract
Microorganisms are effective platforms for the production of a variety of chemicals including biofuels, commodity chemicals, polymers and other natural products. However, deep cellular understanding is required for improvement of current biofuel cell factories to truly transform the Bioeconomy. Modifications in microbial metabolic [...] Read more.
Microorganisms are effective platforms for the production of a variety of chemicals including biofuels, commodity chemicals, polymers and other natural products. However, deep cellular understanding is required for improvement of current biofuel cell factories to truly transform the Bioeconomy. Modifications in microbial metabolic pathways and increased resistance to various types of stress caused by the production of these chemicals are crucial in the generation of robust and efficient production hosts. Recent advances in systems and synthetic biology provide new tools for metabolic engineering to design strategies and construct optimal biocatalysts for the sustainable production of desired chemicals, especially in the case of ethanol and fatty acid production. Yeast is an efficient producer of bioethanol and most of the available synthetic biology tools have been developed for the industrial yeast Saccharomyces cerevisiae. Non-conventional yeast systems have several advantageous characteristics that are not easily engineered such as ethanol tolerance, low pH tolerance, thermotolerance, inhibitor tolerance, genetic diversity and so forth. Currently, synthetic biology is still in its initial steps for studies in non-conventional yeasts such as Yarrowia lipolytica, Kluyveromyces marxianus, Issatchenkia orientalis and Pichia pastoris. Therefore, the development and application of advanced synthetic engineering tools must also focus on these underexploited, non-conventional yeast species. Herein, we review the basic synthetic biology tools that can be applied to the standard S. cerevisiae model strain, as well as those that have been developed for non-conventional yeasts. In addition, we will discuss the recent advances employed to develop non-conventional yeast strains that are efficient for the production of a variety of chemicals through the use of metabolic engineering and synthetic biology. Full article
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Review
Relative Biological Effectiveness of High LET Particles on the Reproductive System and Fetal Development
Life 2020, 10(11), 298; https://doi.org/10.3390/life10110298 - 20 Nov 2020
Cited by 1 | Viewed by 570
Abstract
During a space mission, astronauts are inevitably exposed to space radiation, mainly composed of the particles having high values of linear energy transfer (LET), such as protons, helium nuclei, and other heavier ions. Those high-LET particles could induce severer health damages than low-LET [...] Read more.
During a space mission, astronauts are inevitably exposed to space radiation, mainly composed of the particles having high values of linear energy transfer (LET), such as protons, helium nuclei, and other heavier ions. Those high-LET particles could induce severer health damages than low-LET particles such as photons and electrons. While it is known that the biological effectiveness of a specified type of radiation depends on the distribution of dose in time, type of the cell, and the biological endpoint in respect, there are still large uncertainties regarding the effects of high-LET particles on the reproductive system, gamete, embryo, and fetal development because of the limitation of relevant data from epidemiological and experimental studies. To safely achieve the planned deep space missions to the moon and Mars that would involve young astronauts having reproductive functions, it is crucial to know exactly the relevant radiological effects, such as infertility of the parent and various diseases of the child, and then to conduct proper countermeasures. Thus, in this review, the authors present currently available information regarding the relative biological effectiveness (RBE) of high-LET particles on the deterministic effects related to the reproductive system and embryonic/fetal development for further discussions about the safety of being pregnant after or during a long-term interplanetary mission. Full article
(This article belongs to the Special Issue Radiobiology in Space)
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Article
Rapid Transcriptional Reprogramming Triggered by Alteration of the Carbon/Nitrogen Balance Has an Impact on Energy Metabolism in Nostoc sp. PCC 7120
Life 2020, 10(11), 297; https://doi.org/10.3390/life10110297 - 20 Nov 2020
Cited by 2 | Viewed by 832
Abstract
Nostoc (Anabaena) sp. PCC 7120 is a filamentous cyanobacterial species that fixes N2 to nitrogenous compounds using specialised heterocyst cells. Changes in the intracellular ratio of carbon to nitrogen (C/N balance) is known to trigger major transcriptional reprogramming of the [...] Read more.
Nostoc (Anabaena) sp. PCC 7120 is a filamentous cyanobacterial species that fixes N2 to nitrogenous compounds using specialised heterocyst cells. Changes in the intracellular ratio of carbon to nitrogen (C/N balance) is known to trigger major transcriptional reprogramming of the cell, including initiating the differentiation of vegetative cells to heterocysts. Substantial transcriptional analysis has been performed on Nostoc sp. PCC 7120 during N stepdown (low to high C/N), but not during C stepdown (high to low C/N). In the current study, we shifted the metabolic balance of Nostoc sp. PCC 7120 cultures grown at 3% CO2 by introducing them to atmospheric conditions containing 0.04% CO2 for 1 h, after which the changes in gene expression were measured using RNAseq transcriptomics. This analysis revealed strong upregulation of carbon uptake, while nitrogen uptake and metabolism and early stages of heterocyst development were downregulated in response to the shift to low CO2. Furthermore, gene expression changes revealed a decrease in photosynthetic electron transport and increased photoprotection and reactive oxygen metabolism, as well a decrease in iron uptake and metabolism. Differential gene expression was largely attributed to change in the abundances of the metabolites 2-phosphoglycolate and 2-oxoglutarate, which signal a rapid shift from fluent photoassimilation to glycolytic metabolism of carbon after transition to low CO2. This work shows that the C/N balance in Nostoc sp. PCC 7120 rapidly adjusts the metabolic strategy through transcriptional reprogramming, enabling survival in the fluctuating environment. Full article
(This article belongs to the Special Issue Cellular and Molecular Strategies in Cyanobacterial Survival)
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Review
Analysis of Human Mutations in the Supernumerary Subunits of Complex I
Life 2020, 10(11), 296; https://doi.org/10.3390/life10110296 - 20 Nov 2020
Cited by 1 | Viewed by 840
Abstract
Complex I is the largest member of the electron transport chain in human mitochondria. It comprises 45 subunits and requires at least 15 assembly factors. The subunits can be divided into 14 “core” subunits that carry out oxidation–reduction reactions and proton translocation, as [...] Read more.
Complex I is the largest member of the electron transport chain in human mitochondria. It comprises 45 subunits and requires at least 15 assembly factors. The subunits can be divided into 14 “core” subunits that carry out oxidation–reduction reactions and proton translocation, as well as 31 additional supernumerary (or accessory) subunits whose functions are less well known. Diminished levels of complex I activity are seen in many mitochondrial disease states. This review seeks to tabulate mutations in the supernumerary subunits of humans that appear to cause disease. Mutations in 20 of the supernumerary subunits have been identified. The mutations were analyzed in light of the tertiary and quaternary structure of human complex I (PDB id = 5xtd). Mutations were found that might disrupt the folding of that subunit or that would weaken binding to another subunit. In some cases, it appeared that no protein was made or, at least, could not be detected. A very common outcome is the lack of assembly of complex I when supernumerary subunits are mutated or missing. We suggest that poor assembly is the result of disrupting the large network of subunit interactions that the supernumerary subunits typically engage in. Full article
(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)
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Review
Genome Editing by CRISPR-Cas: A Game Change in the Genetic Manipulation of Chlamydomonas
Life 2020, 10(11), 295; https://doi.org/10.3390/life10110295 - 20 Nov 2020
Cited by 1 | Viewed by 1664
Abstract
Microalgae are promising photosynthetic unicellular eukaryotes among the most abundant on the planet and are considered as alternative sustainable resources for various industrial applications. Chlamydomonas is an emerging model for microalgae to be manipulated by multiple biotechnological tools in order to produce high-value [...] Read more.
Microalgae are promising photosynthetic unicellular eukaryotes among the most abundant on the planet and are considered as alternative sustainable resources for various industrial applications. Chlamydomonas is an emerging model for microalgae to be manipulated by multiple biotechnological tools in order to produce high-value bioproducts such as biofuels, bioactive peptides, pigments, nutraceuticals, and medicines. Specifically, Chlamydomonas reinhardtii has become a subject of different genetic-editing techniques adapted to modulate the production of microalgal metabolites. The main nuclear genome-editing tools available today include zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and more recently discovered the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein (Cas) nuclease system. The latter, shown to have an interesting editing capacity, has become an essential tool for genome editing. In this review, we highlight the available literature on the methods and the applications of CRISPR-Cas for C. reinhardtii genetic engineering, including recent transformation methods, most used bioinformatic tools, best strategies for the expression of Cas protein and sgRNA, the CRISPR-Cas mediated gene knock-in/knock-out strategies, and finally the literature related to CRISPR expression and modification approaches. Full article
(This article belongs to the Special Issue Plant Synthetic Biology)
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Article
Mouthguard Use Effect on the Biomechanical Response of an Ankylosed Maxillary Central Incisor during a Traumatic Impact: A 3-Dimensional Finite Element Analysis
Life 2020, 10(11), 294; https://doi.org/10.3390/life10110294 - 20 Nov 2020
Cited by 2 | Viewed by 587
Abstract
(1) Background: Trauma is a very common experience in contact sports; however, there is an absence of data regarding the effect of athletes wearing mouthguards (MG) associated with ankylosed maxillary central incisor during a traumatic impact. (2) Methods: To evaluate the stress distribution [...] Read more.
(1) Background: Trauma is a very common experience in contact sports; however, there is an absence of data regarding the effect of athletes wearing mouthguards (MG) associated with ankylosed maxillary central incisor during a traumatic impact. (2) Methods: To evaluate the stress distribution in the bone and teeth in this situation, models of maxillary central incisor were created containing cortical bone, trabecular bone, soft tissue, root dentin, enamel, periodontal ligament, and antagonist teeth were modeled. One model received a MG with 4-mm thickness. Both models were subdivided into finite elements. The frictionless contacts were used and a nonlinear dynamic impact analysis was performed in which a rigid object hit the model at 1 m·s−1. For each model, an ankylosed periodontal ligament was simulated totaling 4 different situations. The results were presented in von-Mises stress maps. (3) Results: A higher stress concentration in teeth and bone was observed for the model without a MG and with ankylosed tooth (19.5 and 37.3 MPa, respectively); the most promising mechanical response was calculated for patients with healthy periodontal ligament and MG in position (1.8 and 7.8 MPa, respectively). (4) Conclusions: The MG’s use is beneficial for healthy and ankylosed teeth, since it acts by dampening the generated stresses in bone, dentin, enamel and periodontal ligament. However, patients with ankylosed tooth are more prone to root fracture even when the MG is in position compared to a healthy tooth. Full article
(This article belongs to the Special Issue Exercise Biomechanics and Physiology)
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Article
Anti-Inflammatory Effects of Fermented Lotus Root and Linoleic Acid in Lipopolysaccharide-Induced RAW 264.7 Cells
Life 2020, 10(11), 293; https://doi.org/10.3390/life10110293 - 19 Nov 2020
Cited by 2 | Viewed by 606
Abstract
Inflammation is a protective response of the innate immune system. However, aberrant inflammatory responses lead to various diseases. Lotus root, the edible rhizome of Nelumbo nucifera, is a popular traditional herbal medicine in East Asia. In a previous study, we reported that [...] Read more.
Inflammation is a protective response of the innate immune system. However, aberrant inflammatory responses lead to various diseases. Lotus root, the edible rhizome of Nelumbo nucifera, is a popular traditional herbal medicine in East Asia. In a previous study, we reported that fermented lotus root (FLR) alleviated ethanol/HCl-induced gastric ulcers in rats by modulating inflammation-related genes. However, the mechanisms underlying the anti-inflammatory effects of FLR and its major constituent, linoleic acid (LA), are still largely unknown. In this study, we investigated the anti-inflammatory effects of FLR and LA on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 murine macrophages. We found that FLR inhibited LPS-induced expression of inflammatory mediators through down-regulation of NF-κB activity. Similarly, LA also attenuated LPS-induced inflammatory responses and reduced LPS-induced phosphorylation of proteins associated with NF-κB signaling, such as ERK, JNK, and p38. Overall, our results suggested that FLR and LA may effectively ameliorate inflammatory diseases. Full article
(This article belongs to the Section Pharmaceutical Science)
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Review
The Mycobiota of the Deep Sea: What Omics Can Offer
Life 2020, 10(11), 292; https://doi.org/10.3390/life10110292 - 19 Nov 2020
Cited by 1 | Viewed by 1012
Abstract
The deep sea (>1000 m below sea level) represents one of the most extreme environments of the ocean. Despite exhibiting harsh abiotic conditions such as low temperatures, high hydrostatic pressure, high salinity concentrations, a low input of organic matter, and absence of light, [...] Read more.
The deep sea (>1000 m below sea level) represents one of the most extreme environments of the ocean. Despite exhibiting harsh abiotic conditions such as low temperatures, high hydrostatic pressure, high salinity concentrations, a low input of organic matter, and absence of light, the deep sea encompasses a great fungal diversity. For decades, most knowledge on the fungal diversity of the deep sea was obtained through culture-dependent techniques. More recently, with the latest advances of high-throughput next generation sequencing platforms, there has been a rapid increment in the number of studies using culture-independent techniques. This review brings into the spotlight the progress of the techniques used to assess the diversity and ecological role of the deep-sea mycobiota and provides an overview on how the omics technologies have contributed to gaining knowledge about fungi and their activity in poorly explored marine environments. Finally, current challenges and suggested coordinated efforts to overcome them are discussed. Full article
(This article belongs to the Special Issue Advances in Fungal -Omics)
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Article
Six ‘Must-Have’ Minerals for Life’s Emergence: Olivine, Pyrrhotite, Bridgmanite, Serpentine, Fougerite and Mackinawite
Life 2020, 10(11), 291; https://doi.org/10.3390/life10110291 - 19 Nov 2020
Cited by 4 | Viewed by 1219
Abstract
Life cannot emerge on a planet or moon without the appropriate electrochemical disequilibria and the minerals that mediate energy-dissipative processes. Here, it is argued that four minerals, olivine ([Mg>Fe]2SiO4), bridgmanite ([Mg,Fe]SiO3), serpentine ([Mg,Fe,]2-3Si2O [...] Read more.
Life cannot emerge on a planet or moon without the appropriate electrochemical disequilibria and the minerals that mediate energy-dissipative processes. Here, it is argued that four minerals, olivine ([Mg>Fe]2SiO4), bridgmanite ([Mg,Fe]SiO3), serpentine ([Mg,Fe,]2-3Si2O5[OH)]4), and pyrrhotite (Fe(1−x)S), are an essential requirement in planetary bodies to produce such disequilibria and, thereby, life. Yet only two minerals, fougerite ([Fe2+6xFe3+6(x−1)O12H2(7−3x)]2+·[(CO2−)·3H2O]2−) and mackinawite (Fe[Ni]S), are vital—comprising precipitate membranes—as initial “free energy” conductors and converters of such disequilibria, i.e., as the initiators of a CO2-reducing metabolism. The fact that wet and rocky bodies in the solar system much smaller than Earth or Venus do not reach the internal pressure (≥23 GPa) requirements in their mantles sufficient for producing bridgmanite and, therefore, are too reduced to stabilize and emit CO2—the staple of life—may explain the apparent absence or negligible concentrations of that gas on these bodies, and thereby serves as a constraint in the search for extraterrestrial life. The astrobiological challenge then is to search for worlds that (i) are large enough to generate internal pressures such as to produce bridgmanite or (ii) boast electron acceptors, including imported CO2, from extraterrestrial sources in their hydrospheres. Full article
(This article belongs to the Special Issue Frontiers of Astrobiology)
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Review
Methodologies of Primary HPV Testing Currently Applied for Cervical Cancer Screening
Life 2020, 10(11), 290; https://doi.org/10.3390/life10110290 - 19 Nov 2020
Cited by 1 | Viewed by 720
Abstract
The human papillomavirus is one of the most common sexually transmitted viruses, and an infection from this virus may become persistent, leading to diseases such as cervical cancer. In the past, cytology-based methods such as the Papanicolaou (Pap) test were imperative to identify [...] Read more.
The human papillomavirus is one of the most common sexually transmitted viruses, and an infection from this virus may become persistent, leading to diseases such as cervical cancer. In the past, cytology-based methods such as the Papanicolaou (Pap) test were imperative to identify the disease at a stage where it can be treated. However, since the 1980s where the etiological association of HPV and cervical cancer was identified, new tests began emerging directed towards identifying the virus. Furthermore, as the biology of HPV along with the relationships with its host are elucidated, these tests and treatments further advance. Recently in Europe, there is a movement towards the implementation of HPV testing methodologies in national screening programs to precede cytological testing. These screening strategies are recommended by the European guidelines and the World Health Organization. This review presents the current HPV testing methodologies, their application in organized population-based cervical cancer screening programs based on the most recent European guidelines, and their implementation status in countries in Europe. Full article
(This article belongs to the Section Medical Research)
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Review
Keeping α-Synuclein at Bay: A More Active Role of Molecular Chaperones in Preventing Mitochondrial Interactions and Transition to Pathological States?
Life 2020, 10(11), 289; https://doi.org/10.3390/life10110289 - 19 Nov 2020
Cited by 2 | Viewed by 738
Abstract
The property of molecular chaperones to dissolve protein aggregates of Parkinson-related α-synuclein has been known for some time. Recent findings point to an even more active role of molecular chaperones preventing the transformation of α-synuclein into pathological states subsequently leading to the formation [...] Read more.
The property of molecular chaperones to dissolve protein aggregates of Parkinson-related α-synuclein has been known for some time. Recent findings point to an even more active role of molecular chaperones preventing the transformation of α-synuclein into pathological states subsequently leading to the formation of Lewy bodies, intracellular inclusions containing protein aggregates as well as broken organelles found in the brains of Parkinson’s patients. In parallel, a short motif around Tyr39 was identified as being crucial for the aggregation of α-synuclein. Interestingly, this region is also one of the main segments in contact with a diverse pool of molecular chaperones. Further, it could be shown that the inhibition of the chaperone:α-synuclein interaction leads to a binding of α-synuclein to mitochondria, which could also be shown to lead to mitochondrial membrane disruption as well as the possible proteolytic processing of α-synuclein by mitochondrial proteases. Here, we will review the current knowledge on the role of molecular chaperones in the regulation of physiological functions as well as the direct consequences of impairing these interactions—i.e., leading to enhanced mitochondrial interaction and consequential mitochondrial breakage, which might mark the initial stages of the structural transition of α-synuclein towards its pathological states. Full article
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Review
Functional Roles of RNA-Binding Proteins in Plant Signaling
Life 2020, 10(11), 288; https://doi.org/10.3390/life10110288 - 18 Nov 2020
Cited by 1 | Viewed by 772
Abstract
RNA-binding proteins (RBPs) are typical proteins that bind RNA through single or multiple RNA-binding domains (RBDs). These proteins have a functional role in determining the fate or function of the bound RNAs. A few hundred RBPs were known through in silico prediction based [...] Read more.
RNA-binding proteins (RBPs) are typical proteins that bind RNA through single or multiple RNA-binding domains (RBDs). These proteins have a functional role in determining the fate or function of the bound RNAs. A few hundred RBPs were known through in silico prediction based on computational assignment informed by structural similarity and the presence of classical RBDs. However, RBPs lacking such conventional RBDs were omitted. Owing to the recent mRNA interactome capture technology based on UV-crosslinking and fixing proteins to their mRNA targets followed by affinity capture purification and identification of RBPs by tandem mass spectrometry, several hundreds of RBPs have recently been discovered. These proteome-wide studies have colossally increased the number of proteins implicated in RNA binding and unearthed hundreds of novel RBPs lacking classical RBDs, such as proteins involved in intermediary metabolism. These discoveries provide wide insights into the post-transcriptional gene regulation players and their role in plant signaling, such as environmental stress conditions. In this review, novel discoveries of RBPs are explored, particularly on the evolving knowledge of their role in stress responses. The molecular functions of these RBPs, particularly focusing on those that do not have classical RBDs, are also elucidated at the systems level. Full article
(This article belongs to the Special Issue Plant Proteomics)
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Article
Otoacoustic Emissions in Children with Long-Term Middle Ear Disease
Life 2020, 10(11), 287; https://doi.org/10.3390/life10110287 - 18 Nov 2020
Viewed by 653
Abstract
Introduction: Otoacoustic emissions (OAEs) evaluate the functional status of the cochlea. Repeated otitis media (OM) can cause changes in the peripheral structures of the auditory system, and, in this way, middle ear infection may irreversibly damage the middle ear, or even the cochlea. [...] Read more.
Introduction: Otoacoustic emissions (OAEs) evaluate the functional status of the cochlea. Repeated otitis media (OM) can cause changes in the peripheral structures of the auditory system, and, in this way, middle ear infection may irreversibly damage the middle ear, or even the cochlea. Objectives: To analyze the results of transiently evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) in individuals with a history of OM. Method: Participants with 8 to 16 years of schooling were split into two groups: a control group (CG) of 50 subjects who had no history of otological disease and an experimental group (EG) of 50 subjects who had a history of recurrent otitis in childhood and had consequently undergone myringotomy to insert bilateral ventilation tubes. All children underwent basic audiological assessment (tonal audiometry, speech audiometry, and immittance testing) and otoacoustic emission testing (TEOAEs and DPOAEs). Results: There were no significant differences between the groups when audiometrically tested via air and bone conduction. OAEs were found in all CG subjects. For the EG, there were no TEOAE responses in 17 ears and no DPOAEs in nine ears; response amplitudes were lower at all frequencies. The emission level and the signal-to-noise ratio were statistically different between the two groups, and OAEs in the EG were statistically smaller compared to the GC. Conclusion: In the EG, responses were more likely to be absent and were of statistically smaller amplitude compared to the CG. A history of repeated OM apparently interferes with the generation and transmission of TEOAEs and DPOAEs. Full article
Review
Hydrogen-Deuterium Exchange Mass Spectrometry: A Novel Structural Biology Approach to Structure, Dynamics and Interactions of Proteins and Their Complexes
Life 2020, 10(11), 286; https://doi.org/10.3390/life10110286 - 15 Nov 2020
Viewed by 1139
Abstract
Hydrogen/Deuterium eXchange Mass Spectrometry (HDX-MS) is a rapidly evolving technique for analyzing structural features and dynamic properties of proteins. It may stand alone or serve as a complementary method to cryo-electron-microscopy (EM) or other structural biology approaches. HDX-MS is capable of providing information [...] Read more.
Hydrogen/Deuterium eXchange Mass Spectrometry (HDX-MS) is a rapidly evolving technique for analyzing structural features and dynamic properties of proteins. It may stand alone or serve as a complementary method to cryo-electron-microscopy (EM) or other structural biology approaches. HDX-MS is capable of providing information on individual proteins as well as large protein complexes. Owing to recent methodological advancements and improving availability of instrumentation, HDX-MS is becoming a routine technique for some applications. When dealing with samples of low to medium complexity and sizes of less than 150 kDa, conformation and ligand interaction analyses by HDX-MS are already almost routine applications. This is also well supported by the rapid evolution of the computational (software) background that facilitates the analysis of the obtained experimental data. HDX-MS can cope at times with analytes that are difficult to tackle by any other approach. Large complexes like viral capsids as well as disordered proteins can also be analyzed by this method. HDX-MS has recently become an established tool in the drug discovery process and biopharmaceutical development, as it is now also capable of dissecting post-translational modifications and membrane proteins. This mini review provides the reader with an introduction to the technique and a brief overview of the most common applications. Furthermore, the most challenging likely applications, the analyses of glycosylated and membrane proteins, are also highlighted. Full article
(This article belongs to the Special Issue Current Approaches in Molecular Enzymology)
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Article
Efficacy of Applying Hyaluronic Acid Gels in the Primary Prevention of Intrauterine Adhesion after Hysteroscopic Myomectomy: A Meta-Analysis of Randomized Controlled Trials
Life 2020, 10(11), 285; https://doi.org/10.3390/life10110285 - 15 Nov 2020
Cited by 5 | Viewed by 782
Abstract
Intrauterine adhesion (IUA), which mainly occurs after intrauterine surgery or an inflammatory process, is an important but often neglected condition in women of reproductive age. The presentation of IUA varies greatly, ranging from symptom-free to severe, with amenorrhea or infertility. With much advanced [...] Read more.
Intrauterine adhesion (IUA), which mainly occurs after intrauterine surgery or an inflammatory process, is an important but often neglected condition in women of reproductive age. The presentation of IUA varies greatly, ranging from symptom-free to severe, with amenorrhea or infertility. With much advanced development of intrauterine instruments, more intrauterine diseases can be successfully cured by hysteroscopic surgery. Among these, submucosal myoma is one of the best examples. Submucosal myomas are often related to abnormal bleeding, anemia, and possible infertility or miscarriage. However, submucosal myoma after hysteroscopic myomectomy may be complicated by IUA in various grades of severity, and its incidence and prevalence might be nearly one-quarter to one-third of patients, suggesting an urgent need for efforts to decrease the risk of developing IUA after hysteroscopic myomectomy. Many strategies have been reported to be useful for this purpose, and intrauterine application of anti-adhesive gels, such as polyethylene oxide–sodium carboxymethylcellulose (PEO-NaCMC) or auto-crosslinked hyaluronic acid (ACHA), has become increasingly popular in routine clinical practice. This meta-analysis is aimed at investigating the effect of ACHA on the primary prevention of IUA formation after hysteroscopic myomectomy. A pooled analysis of three studies (hysteroscopic surgeries for fibroids, polyps, and septum) including 242 women showed that using PEO-NaCMC or ACHA gel decreased the IUA rate with an odds ratio (OR) of 0.364 (95% confidence interval (CI) 0.189–0.703, p = 0.03). Pooled analysis of two studies that limited the use of ACHA in 119 women showed that the application of ACHA gel for the primary prevention of IUA in patients after hysteroscopic myomectomy led to a statistically significant reduction of the development of IUA postoperatively (OR 0.285, 95% CI 0.116–0.701, p = 0.006). All of this suggests that the use of ACHA gel in patients after hysteroscopic myomectomy could significantly reduce de novo IUA, although more evidence is needed. Full article
(This article belongs to the Special Issue Reproductive Health Concerns for Women)
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Review
Effects of Resistance Exercise on Balance Ability: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Life 2020, 10(11), 284; https://doi.org/10.3390/life10110284 - 15 Nov 2020
Cited by 1 | Viewed by 1289
Abstract
With this systematic review, we explored whether resistance exercise (RE) could be used to improve balance in addition to muscular strength and power. Scientific databases were searched for randomized controlled trials that investigated the effects of RE on the performance of various balance [...] Read more.
With this systematic review, we explored whether resistance exercise (RE) could be used to improve balance in addition to muscular strength and power. Scientific databases were searched for randomized controlled trials that investigated the effects of RE on the performance of various balance tests. Studies were considered if they involved healthy participants of any age group. Thirteen studies were included in the meta-analysis. The results showed moderate to large improvements in balance ability following RE in older adults, as reflected in functional reach test (mean difference (MD): +4.22 cm, p < 0.001), single-leg standing test (MD: +1.9–37.6 s, p < 0.001) and timed-up-and-go test (MD: −0.55 s; p = 0.002). Moderate to large improvements following RE were seen in adults in star excursion balance test (MD: +4.09–5.17 cm; p = 0.001–0.020), but not for Y-balance test score (MD: +4.94%, p = 0.14). The results implicate that RE interventions may significantly improve balance ability in adults and older adults. Therefore, RE could be used to improve balance in these populations, while further studies are needed to investigate children populations. Performing RE alone could be a time-efficient compromise for individuals who are unwilling or unable to perform large volumes of exercise or different exercise modalities. Full article
(This article belongs to the Special Issue Exercise Biomechanics and Physiology)
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Article
Effect of Hyperbaric Oxygen Therapy on Acute Liver Injury and Survival in a Rat Cecal Slurry Peritonitis Model
Life 2020, 10(11), 283; https://doi.org/10.3390/life10110283 - 15 Nov 2020
Viewed by 596
Abstract
Background: The effects of hyperbaric oxygen therapy (HBOT) in sepsis remain unclear. This study evaluated its effects on acute liver injury and survival in a rat model. Methods: Cecal slurry peritonitis was induced in male rats, which were then randomly allocated into the [...] Read more.
Background: The effects of hyperbaric oxygen therapy (HBOT) in sepsis remain unclear. This study evaluated its effects on acute liver injury and survival in a rat model. Methods: Cecal slurry peritonitis was induced in male rats, which were then randomly allocated into the HBOT and control groups. In the survival experiment, six 90 min HBOT sessions (2.6 atmospheres absolute 100% oxygen) were performed over 48 h; the survival rate was determined 14 days after sepsis induction. In the acute liver injury experiment, three HBOT sessions were performed, followed by liver and plasma harvesting, 24 h after sepsis induction. Serum levels of alanine aminotransferase (ALT), interleukin (IL)-6, and IL-10 were measured, and the hepatic injury scores were determined. Reactive oxygen species (ROS) generation was detected by 2′,7′-dihydrodichlorofluorescein diacetate (H2DCF-DA) assay. Western blot assays assessed protein kinase B (Akt), phosphorylated-Akt (p-Akt), glycogen synthase kinase (GSK)-3β, phosphorylated-GSK-3β, and cleaved caspase-3 levels. Results: Survival in the HBOT group (57.1%) was significantly higher than that in the controls (12.5%, p = 0.029), whereas IL-6, IL-10, and ALT levels were significantly lower in the HBOT group. The ROS generation was significantly inhibited to a greater extent in the HBOT group than in the control group. Additionally, in the HBOT group, the p-Akt and p-GSK-3β increased significantly and cleaved caspase-3 levels decreased significantly. Conclusions: HBOT showed a beneficial effect on acute liver injury and rat survival by enhancing the Akt signaling pathway and decreasing apoptosis. Full article
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Article
Kinematics and Kinetics of Bulgarian-Bag-Overloaded Sprints in Young Athletes
Life 2020, 10(11), 282; https://doi.org/10.3390/life10110282 - 15 Nov 2020
Cited by 1 | Viewed by 824
Abstract
Background: Effective sprinting requires large acceleration capabilities. To accelerate, large amount of force must be produced and applied effectively. The use of different implements such as sleds and vests can increase the amount of force produced and alter sprinting effectiveness. We propose the [...] Read more.
Background: Effective sprinting requires large acceleration capabilities. To accelerate, large amount of force must be produced and applied effectively. The use of different implements such as sleds and vests can increase the amount of force produced and alter sprinting effectiveness. We propose the use of increasing overload via the Bulgarian Bag (BB) as a means to modify athletes’ sprint and acutely increase force and power production. Methods: 24 young athletes performed three sprints over 20 m in three different conditions: unloaded (BW) and loaded with BB weighing 2.5% (BB2.5) and 5% (BB5) of the athlete’s body mass. Sprint times at 2.5, 5, 10, 15, and 20 m were acquired and used to compute the force–velocity relationship for the sprints. Maximal velocity (V0), peak force (F0), peak power (PP), and decrease in ratio of force (DRF) were computed. Results: the additional load caused a decrease in sprint times (p < 0.05) and V0 (p = 0.028), conversely no differences were found for F0 (p = 0.21), PP (p = 0.50), and DRF (p = 0.83). Conclusions: Based on those findings, BB can be an alternative method to effectively overload sprint training toward improving sprinting performance. Full article
(This article belongs to the Special Issue Exercise Biomechanics and Physiology)
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Article
Paleozoic–Mesozoic Eustatic Changes and Mass Extinctions: New Insights from Event Interpretation
Life 2020, 10(11), 281; https://doi.org/10.3390/life10110281 - 14 Nov 2020
Viewed by 775
Abstract
Recent eustatic reconstructions allow for reconsidering the relationships between the fifteen Paleozoic–Mesozoic mass extinctions (mid-Cambrian, end-Ordovician, Llandovery/Wenlock, Late Devonian, Devonian/Carboniferous, mid-Carboniferous, end-Guadalupian, end-Permian, two mid-Triassic, end-Triassic, Early Jurassic, Jurassic/Cretaceous, Late Cretaceous, and end-Cretaceous extinctions) and global sea-level changes. The relationships between eustatic rises/falls [...] Read more.
Recent eustatic reconstructions allow for reconsidering the relationships between the fifteen Paleozoic–Mesozoic mass extinctions (mid-Cambrian, end-Ordovician, Llandovery/Wenlock, Late Devonian, Devonian/Carboniferous, mid-Carboniferous, end-Guadalupian, end-Permian, two mid-Triassic, end-Triassic, Early Jurassic, Jurassic/Cretaceous, Late Cretaceous, and end-Cretaceous extinctions) and global sea-level changes. The relationships between eustatic rises/falls and period-long eustatic trends are examined. Many eustatic events at the mass extinction intervals were not anomalous. Nonetheless, the majority of the considered mass extinctions coincided with either interruptions or changes in the ongoing eustatic trends. It cannot be excluded that such interruptions and changes could have facilitated or even triggered biodiversity losses in the marine realm. Full article
(This article belongs to the Section Paleontology)
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Article
Dual RNase and β-lactamase Activity of a Single Enzyme Encoded in Archaea
Life 2020, 10(11), 280; https://doi.org/10.3390/life10110280 - 14 Nov 2020
Cited by 2 | Viewed by 760
Abstract
β-lactam antibiotics have a well-known activity which disturbs the bacterial cell wall biosynthesis and may be cleaved by β-lactamases. However, these drugs are not active on archaea microorganisms, which are naturally resistant because of the lack of β-lactam target in their cell wall. [...] Read more.
β-lactam antibiotics have a well-known activity which disturbs the bacterial cell wall biosynthesis and may be cleaved by β-lactamases. However, these drugs are not active on archaea microorganisms, which are naturally resistant because of the lack of β-lactam target in their cell wall. Here, we describe that annotation of genes as β-lactamases in Archaea on the basis of homologous genes is a remnant of identification of the original activities of this group of enzymes, which in fact have multiple functions, including nuclease, ribonuclease, β-lactamase, or glyoxalase, which may specialized over time. We expressed class B β-lactamase enzyme from Methanosarcina barkeri that digest penicillin G. Moreover, while weak glyoxalase activity was detected, a significant ribonuclease activity on bacterial and synthetic RNAs was demonstrated. The β-lactamase activity was inhibited by β-lactamase inhibitor (sulbactam), but its RNAse activity was not. This gene appears to have been transferred to the Flavobacteriaceae group especially the Elizabethkingia genus, in which the expressed gene shows a more specialized activity on thienamycin, but no glyoxalase activity. The expressed class C-like β-lactamase gene, from Methanosarcina sp., also shows hydrolysis activity on nitrocefin and is more closely related to DD-peptidase enzymes. Our findings highlight the need to redefine the nomenclature of β-lactamase enzymes and the specification of multipotent enzymes in different ways in Archaea and bacteria over time. Full article
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Article
Heterocyst Development and Diazotrophic Growth of Anabaena variabilis under Different Nitrogen Availability
Life 2020, 10(11), 279; https://doi.org/10.3390/life10110279 - 13 Nov 2020
Cited by 2 | Viewed by 605
Abstract
Nitrogen is globally limiting primary production in the ocean, but some species of cyanobacteria can carry out nitrogen (N) fixation using specialized cells known as heterocysts. However, the effect of N sources and their availability on heterocyst development is not yet fully understood. [...] Read more.
Nitrogen is globally limiting primary production in the ocean, but some species of cyanobacteria can carry out nitrogen (N) fixation using specialized cells known as heterocysts. However, the effect of N sources and their availability on heterocyst development is not yet fully understood. This study aimed to evaluate the effect of various inorganic N sources on the heterocyst development and cellular growth in an N-fixing cyanobacterium, Anabaena variabilis. Growth rate, heterocyst development, and cellular N content of the cyanobacteria were examined under varying nitrate and ammonium concentrations. A. variabilis exhibited high growth rate both in the presence and absence of N sources regardless of their concentration. Ammonium was the primary source of N in A. variabilis. Even the highest concentrations of both nitrate (1.5 g L−1 as NaNO3) and ammonium (0.006 g L−1 as Fe-NH4-citrate) did not exhibit an inhibitory effect on heterocyst development. Heterocyst production positively correlated with the cell N quota and negatively correlated with vegetative cell growth, indicating that both of the processes were interdependent. Taken together, N deprivation triggers heterocyst production for N fixation. This study outlines the difference in heterocyst development and growth in A. variabilis under different N sources. Full article
(This article belongs to the Special Issue Cellular and Molecular Strategies in Cyanobacterial Survival)
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Article
Macrobiont: Cradle for the Origin of Life and Creation of a Biosphere
Life 2020, 10(11), 278; https://doi.org/10.3390/life10110278 - 12 Nov 2020
Cited by 3 | Viewed by 988
Abstract
Although the cellular microorganism is the fundamental unit of biology, the origin of life (OoL) itself is unlikely to have occurred in a microscale environment. The macrobiont (MB) is the macro-scale setting where life originated. Guided by the methodologies of Systems Analysis, we [...] Read more.
Although the cellular microorganism is the fundamental unit of biology, the origin of life (OoL) itself is unlikely to have occurred in a microscale environment. The macrobiont (MB) is the macro-scale setting where life originated. Guided by the methodologies of Systems Analysis, we focus on subaerial ponds of scale 3 to 300 m diameter. Within such ponds, there can be substantial heterogeneity, on the vertical, horizontal, and temporal scales, which enable multi-pot prebiotic chemical evolution. Pond size-sensitivities for several figures of merit are mathematically formulated, leading to the expectation that the optimum pond size for the OoL is intermediate, but biased toward smaller sizes. Sensitivities include relative access to nutrients, energy sources, and catalysts, as sourced from geological, atmospheric, hydrospheric, and astronomical contributors. Foreshores, especially with mudcracks, are identified as a favorable component for the success of the macrobiont. To bridge the gap between inanimate matter and a planetary-scale biosphere, five stages of evolution within the macrobiont are hypothesized: prebiotic chemistry → molecular replicator → protocell → macrobiont cell → colonizer cell. Comparison of ponds with other macrobionts, including hydrothermal and meteorite settings, allows a conclusion that more than one possible macrobiont locale could enable an OoL. Full article
(This article belongs to the Special Issue Frontiers of Astrobiology)
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Review
Metabolic Alterations Caused by Defective Cardiolipin Remodeling in Inherited Cardiomyopathies
Life 2020, 10(11), 277; https://doi.org/10.3390/life10110277 - 11 Nov 2020
Cited by 3 | Viewed by 881
Abstract
The heart is the most energy-consuming organ in the human body. In heart failure, the homeostasis of energy supply and demand is endangered by an increase in cardiomyocyte workload, or by an insufficiency in energy-providing processes. Energy metabolism is directly associated with mitochondrial [...] Read more.
The heart is the most energy-consuming organ in the human body. In heart failure, the homeostasis of energy supply and demand is endangered by an increase in cardiomyocyte workload, or by an insufficiency in energy-providing processes. Energy metabolism is directly associated with mitochondrial redox homeostasis. The production of toxic reactive oxygen species (ROS) may overwhelm mitochondrial and cellular ROS defense mechanisms in case of heart failure. Mitochondria are essential cell organelles and provide 95% of the required energy in the heart. Metabolic remodeling, changes in mitochondrial structure or function, and alterations in mitochondrial calcium signaling diminish mitochondrial energy provision in many forms of cardiomyopathy. The mitochondrial respiratory chain creates a proton gradient across the inner mitochondrial membrane, which couples respiration with oxidative phosphorylation and the preservation of energy in the chemical bonds of ATP. Akin to other mitochondrial enzymes, the respiratory chain is integrated into the inner mitochondrial membrane. The tight association with the mitochondrial phospholipid cardiolipin (CL) ensures its structural integrity and coordinates enzymatic activity. This review focuses on how changes in mitochondrial CL may be associated with heart failure. Dysfunctional CL has been found in diabetic cardiomyopathy, ischemia reperfusion injury and the aging heart. Barth syndrome (BTHS) is caused by an inherited defect in the biosynthesis of cardiolipin. Moreover, a dysfunctional CL pool causes other types of rare inherited cardiomyopathies, such as Sengers syndrome and Dilated Cardiomyopathy with Ataxia (DCMA). Here we review the impact of cardiolipin deficiency on mitochondrial functions in cellular and animal models. We describe the molecular mechanisms concerning mitochondrial dysfunction as an incitement of cardiomyopathy and discuss potential therapeutic strategies. Full article
(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)
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Article
Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis
Life 2020, 10(11), 276; https://doi.org/10.3390/life10110276 - 08 Nov 2020
Cited by 2 | Viewed by 762
Abstract
Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although their predictive tools have not yet completely developed. Here, we aimed to exam the role of 70-gene chromosomal instability signature (CIN70) in cancers, and its association with previous predictors, [...] Read more.
Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although their predictive tools have not yet completely developed. Here, we aimed to exam the role of 70-gene chromosomal instability signature (CIN70) in cancers, and its association with previous predictors, tumor mutation burden (TMB), and microsatellite instability (MSI), for patients undergoing ICIs, as well as the possible predictive value for ICIs. We examined the association of CIN70 with TMB and MSI, as well as the impact of these biomarkers on the survival of 33 cancer cohorts from The Cancer Genome Atlas (TCGA) databank. The predictive value of the ICIs of CIN70 in previously published reports was also validated. Using the TCGA dataset, CIN70 scores were frequently (either positively or negatively) associated with TMB, but were only significantly associated with MSI status in three types of cancer. In addition, our current study showed that all TMB, MSI, and CIN70 had their own prognostic values for survival in patients with various cancers, and that they could be cancer type-specific. In two validation cohorts (melanoma by Hugo et al. and urothelial cancer by Snyder et al.), no significant difference of CIN70 scores was found between responders and non-responders (p-value = 0.226 and 0.108, respectively). In addition, no overall survival difference was noted between patients with a high CIN70 and those with a low CIN70 (p-value = 0.106 and 0.222, respectively). In conclusion, the current study, through a comprehensive bioinformatics analysis, demonstrated a correlation between CIN70 and TMB, but CIN70 is not the predictor for cancer patients undergoing ICIs. Future prospective studies are warranted to validate these findings. Full article
(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)
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