bluuebunny/crossref_metadata_2025 huggingface dataset:
840 Myostatin Deficiency Inhibits Muscle Wasting and Improves Bacterial Clearance and Survival in Septic Mice
Authors: Kaneki Masao , Kobayashi Masayuki , Kasamatsu Shingo , Yasuhara Shingo , Shinozaki Shohei
Published: March 2020

Introduction

Sepsis is a leading cause of the mortality of burn patients. Muscle wasting is a major complication of sepsis and burn injury and negatively affects clinical outcomes of patients with sepsis and burn injury. Myostatin (MSTN) is a myokine that causes muscle atrophy by activating the activin type 2 receptor (ActRII) pathway and myostatin deficiency increases skeletal muscle mass. However, a role of myostatin in critical illness (e.g., sepsis, burn injury)-induced muscle wasting has not yet been investigated. Moreover, a role of muscle wasting in immune suppression and mortality in sepsis is unknown.

Methods

Sepsis was induced by cecum ligation and puncture (CLP) in male MSTN-deficient mice at 8 weeks of age and age- and body weight (BW)-matched wild type (WT) mice. Survival was monitored for 14 days. Bacterial clearance was evaluated at 16 h after CLP by measuring bacterial load in the peritoneal cavity and circulation. The weight of gastrocnemius (GC), tibialis anterior (TA) and soleus (SOL) muscle and cross-sectional areas of GC were measured before and at 14 days after CLP. To evaluate neutrophil organ infiltration, myeloperoxidase (MPO) activity was measured in the liver and kidney at 16 h after CLP. To evaluate liver dysfunction, acute kidney injury and inflammatory response, plasma levels of AST, ALT, NGAL and high mobility group box 1 (HMGB1) were measured at 16 h after CLP. Protein expression of Murf-1 and Atrogin-1, key players in muscle wasting, and ActRIIB was evaluated in GC muscle by immunoblotting at 3 days and 16 h after CLP, respectively.

Results

MSTN deficiency increased skeletal muscle mass and inhibited sepsis-induced muscle wasting compared with BW-matched WT mice. Sepsis-induced increase in Murf-1, but not Atrogin-1, expression in muscle was attenuated by MSTN deficiency. CLP increased protein expression of ActRIIB in muscle. Moreover, MSTN deficiency reduced mortality of septic mice compared with age- and BW-matched WT mice. MSTN deficiency improved bacterial clearance and ameliorated increases in MPO activity in the liver and kidney and plasma concentrations of AST, ALT, NGAL and HMGB1 in septic mice.

Conclusions

Our data showed that MSTN deficiency inhibited muscle wasting and improved bacterial clearance and survival in septic mice. These data indicate that MSTN plays an important role in sepsis-induced muscle wasting. Moreover, our findings suggest that muscle wasting may not be just a complication of sepsis but a driver of sepsis development contributing to mortality of septic mice. This study also raises the possibility that muscle wasting and/or activation of the MSTN-ActRII pathway may exacerbate sepsis-induced immune dysfunction.

Applicability of Research to Practice

Our study identifies the MSTN-ActRII pathway as a novel, potential molecular target to ameliorate muscle wasting and improve survival of septic burned patients.
862 Challenges and Lessons Learned from Opioid Pharmacogenetic Studies in Burn Patients
Authors: Grimsrud Kristin , Palmieri Tina L
Published: March 2020

Introduction

”One-size fits all” opioid dosing often results in a lack of efficacy or toxic consequences. Patients are heterogeneous; their drug sensitivity varies, potentially impacting therapeutic outcomes. Implementation of pharmacogenetic testing in the clinical setting is needed to improve precision dosing, especially in the critically ill (e.g. burns). However, due to the lack of comprehensive data addressing the functional impact of genetic variants, universal implementation of genetic screening is not yet possible. While animal models provide valuable data, they do not capture the vast heterogeneity and comorbidities of patients. Clinical pharmacogenetic studies are needed to advance our understanding of genetic variability and clinical impacts on opioid efficacy. The purpose of this report is to describe the challenges of clinical opioid pharmacogenetic studies in burn patients.

Methods

We performed two studies: 1) a pilot study evaluating CYP gene haplotypes in 13 adult burn patients receiving fentanyl using remnant samples and 2) a pediatric burn patient fentanyl pharmacogenetic study. In the pediatric study, we initially screened with a customized 18 gene panel (opioid pathway specific), and later expanded to whole exome analysis.

Results

We identified 3 adult slow-metabolizers, one with a CYP3A4 and two with CYP2D6 haplotypes and an average of 80+ variants identified in the 18 genes in preliminary analysis of pediatric patients. Multiple challenges were identified in conducting clinical observational studies. Although remnant samples can be hypothesis-generating, clinical data linkage is limited, decreasing the ability for covariate analysis to investigate clinical factors contributing to altered fentanyl metabolism. The use of a commercial haplotype panel, while convenient, only identifies known haplotypes and doesn’t identify all variants in patients. Research protocols must be tailored to clinical workflow. Repeated dosing of fentanyl, which is standard of care but may not be detailed in medical record charting, predisposes research analysis to inaccuracies. Sparse blood sampling, errors in blood draw methodology and loss of vascular access, particularly in pediatrics, can render data sets unanalyzable.

Conclusions

While we have faced many challenges, overall, these studies have produced valuable data to enable better future clinical research design. Educating bedside nurses on study goals, teaching investigators about clinical workflow, and trouble-shooting proper sample collection and charting are essential elements of a successful study. Finally, minimizing sample volume and optimizing sample time points allows for better study adherence and more accurate analysis.

Applicability of Research to Practice

Lessons learned from these studies will aid in the optimization of study design of future burns pharmacogenetic clinical studies.
Analysis of Fusarium graminearum Species Complex from Freshly Harvested Rice in Jiangsu Province (China)
Authors: Dong Fei , Zhang Xiao , Xu Jian Hong , Shi Jian Rong , Lee Yin-Won , Chen Xin Yuan , Li Yun Peng , Mokoena Mduduzi P. , Olaniran Ademola O.
Published: March 2020

Members of Fusarium graminearum species complex (FGSC) are the major pathogens that cause Fusarium head blight (FHB) in cereals worldwide. Symptoms of FHB on rice, including dark staining or browning of rice glumes, were recently observed in Jiangsu Province, China. To improve our understanding of the pathogens involved, 201 FGSC isolates were obtained from freshly harvested rice samples and identified by phylogenetic analyses. Among the 201 FGSC isolates, 196 were F. asiaticum and the remaining 5 were F. graminearum. Trichothecene chemotype and chemical analyses showed that 68.4% of the F. asiaticum isolates were the 3-acetyldeoxynivalenol (3ADON) chemotype and the remainder were the nivalenol (NIV) chemotype. All of the F. graminearum isolates were the 15-acetyldeoxynivalenol chemotype. Pathogenicity assays showed that both the 3ADON and NIV chemotypes of F. asiaticum could infect wheat and rice spikes. FHB severity and trichothecene toxin analysis revealed that F. asiaticum with the NIV chemotype was less aggressive than that with the 3ADON chemotype in wheat, while the NIV-producing strains were more virulent than the 3ADON-producing strains in rice. F. asiaticum isolates with different chemotypes did not show significant differences in mycelial growth, sporulation, conidial dimensions, or perithecial production. These findings would provide useful information for developing management strategies for the control of FHB in China.
Microstructure and crystallography of the wall plates of the giant barnacleAustromegabalanus psittacus: a material organized by crystal growth
Authors: Checa Antonio G. , González-Segura Alicia , Rodríguez-Navarro Alejandro B. , Lagos Nelson A.
Published: March 2020

In biomineralization, it is essential to know the microstructural and crystallographic organization of natural hard tissues. This knowledge is virtually absent in the case of barnacles. Here, we have examined the crystal morphology and orientation of the wall plates of the giant barnacleAustromegabalanus psittacusby means of optical and electron microscopy, and electron backscatter diffraction. The wall plates are made of calcite grains, which change in morphology from irregular to rhombohedral, except for the radii and alae, where fibrous calcite is produced. Both the grains and fibres arrange into bundles made of crystallographically co-oriented units, which grow onto each other epitaxially. We call these areas crystallographically coherent regions (CCRs). Each CCR elongates and disposes itsc-axis perpendicularly or at a high angle to the growth surfaces, whereas thea-axes of adjacent CCRs differ in orientation. In the absence of obvious organic matrices, this pattern of organization is interpreted to be produced by purely crystallographic processes. In particular, due to crystal competition, CCRs orient their fastest growth axes perpendicular to the growth surface. Since each CCR is an aggregate of grains, the fastest growth axis is that along which crystals stack up more rapidly, that is, the crystallographicc-axis in granular calcite. In summary, the material forming the wall plates of the studied barnacles is under very little biological control and the main role of the mantle cells is to provide the construction materials to the growth front.
A novel route to cyclic dominance in voluntary social dilemmas
Authors: Guo Hao , Song Zhao , Geček Sunčana , Li Xuelong , Jusup Marko , Perc Matjaž , Moreno Yamir , Boccaletti Stefano , Wang Zhen
Published: March 2020

Cooperation is the backbone of modern human societies, making it a priority to understand how successful cooperation-sustaining mechanisms operate. Cyclic dominance, a non-transitive set-up comprising at least three strategies wherein the first strategy overrules the second, which overrules the third, which, in turn, overrules the first strategy, is known to maintain biodiversity, drive competition between bacterial strains, and preserve cooperation in social dilemmas. Here, we present a novel route to cyclic dominance in voluntary social dilemmas by adding to the traditional mix of cooperators, defectors and loners, a fourth player type, risk-averse hedgers, who enact tit-for-tat upon paying a hedging cost to avoid being exploited. When this cost is sufficiently small, cooperators, defectors and hedgers enter a loop of cyclic dominance that preserves cooperation even under the most adverse conditions. By contrast, when the hedging cost is large, hedgers disappear, consequently reverting to the traditional interplay of cooperators, defectors, and loners. In the interim region of hedging costs, complex evolutionary dynamics ensues, prompting transitions between states with two, three or four competing strategies. Our results thus reveal that voluntary participation is but one pathway to sustained cooperation via cyclic dominance.
On the relations of phase separation and Hi-C maps to epigenetics
Authors: Singh Prim B. , Newman Andrew G.
Published: March 2020

The relationship between compartmentalization of the genome and epigenetics is long and hoary. In 1928, Heitz defined heterochromatin as the largest differentiated chromatin compartment in eukaryotic nuclei. Müller's discovery of position-effect variegation in 1930 went on to show that heterochromatin is a cytologically visible state of heritable (epigenetic) gene repression. Current insights into compartmentalization have come from a high-throughput top-down approach where contact frequency (Hi-C) maps revealed the presence of compartmental domains that segregate the genome into heterochromatin and euchromatin. It has been argued that the compartmentalization seen in Hi-C maps is owing to the physiochemical process of phase separation. Oddly, the insights provided by these experimental and conceptual advances have remained largely silent on how Hi-C maps and phase separation relate to epigenetics. Addressing this issue directly in mammals, we have made use of a bottom-up approach starting with the hallmarks of constitutive heterochromatin, heterochromatin protein 1 (HP1) and its binding partner the H3K9me2/3 determinant of the histone code. They are key epigenetic regulators in eukaryotes. Both hallmarks are also found outside mammalian constitutive heterochromatin as constituents of larger (0.1–5 Mb) heterochromatin-likedomains and smaller (less than 100 kb) complexes. The well-documented ability of HP1 proteins to function as bridges between H3K9me2/3-marked nucleosomes contributes to polymer–polymer phase separation that packages epigenetically heritable chromatin states during interphase. Contacts mediated by HP1 ‘bridging’ are likely to have been detected in Hi-C maps, as evidenced by the B4 heterochromatic subcompartment that emerges from contacts between large KRAB-ZNF heterochromatin-likedomains. Further, mutational analyses have revealed a finer, innate, compartmentalization in Hi-C experiments that probably reflect contacts involving smaller domains/complexes. Proteins that bridge (modified) DNA and histones in nucleosomal fibres—where the HP1–H3K9me2/3 interaction represents the most evolutionarily conserved paradigm—could drive and generate the fundamental compartmentalization of the interphase nucleus. This has implications for the mechanism(s) that maintains cellular identity, be it a terminally differentiated fibroblast or a pluripotent embryonic stem cell.
Explicit Cartesian oval as a superconic surface for stigmatic imaging optical systems with real or virtual source or image
Authors: Silva-Lora Alberto , Torres Rafael
Published: March 2020

Cartesian ovals, also known as rigorously stigmatic surfaces, are the simplest optical systems capable of producing a perfect point image. Exist both implicit and explicit expressions to represent these surfaces, but they treat both refractive and reflective surfaces independently. Because of the complexity of explicit expressions, the ray-tracing techniques for these surfaces are implemented using third-party software. In this paper, we express Cartesian ovals as a degenerated superconic curve and get a new explicit formulation for Cartesian ovals capable of treating image formation using both object and image points, either real or virtual, and in this formulation can deal with both reflective and refractive rigorously stigmatic surfaces. Finally, using the resultant expressions and the vector Snell–Descartes Law, we propose a self-contained analytical ray-tracing technique for all these surfaces.
Halomonas piezotolerans sp. nov., a multiple-stress-tolerant bacterium isolated from a deep-sea sediment sample of the New Britain Trench
Authors: Yan Fangfang , Fang Jiasong , Cao Junwei , Wei Yuli , Liu Rulong , Wang Li , Xie Zhe
Published: March 2020

A piezotolerant, H2O2-tolerant, heavy-metal-tolerant, slightly halophilic bacterium (strain NBT06E8T) was isolated from a deep-sea sediment sample collected from the New Britain Trench at depth of 8900 m. The strain was aerobic, motile, Gram-stain-negative, rod-shaped, oxidase-positive and catalase-positive. Growth of the strain was observed at 4–45 °C (optimum, 30 °C), at pH 5–11 (optimum, pH 8–9) and in 0.5–21 % (w/v) NaCl (optimum, 3–7 %). The optimum pressure for growth was 0.1–30 MPa with tolerance up to 60 MPa. Under optimum growth conditions, the strain could tolerate 15 mM H2O2. Resuls of 16S rRNA gene sequence analysis showed that strain NBT06E8T is closely related to

Halomonas aquamarina

DSM 30161T (99.5%),

Halomonas meridiana

DSM 5425T (99.43%) and

Halomonas axialensis

Althf1T (99.35%). The digital DNA–DNA hybridization values between strain NBT06E8T and the three related type strains,

H. aquamarina

,

H. meridiana

and

H. axialensis

, were 30.5±2.4 %, 30.7±2.5% and 31.5±2.5 %, respectively. The average nucleotide identity values between strain NBT06E8T and the three related type strains were 86.26, 86.26 and 83.63 %, respectively. The major fatty acids were summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c) and C16 : 0. The predominant respiratory quinone detected was ubiquinone-9 (Q-9). Based on its phenotypic and phylogenetic characteristics, we conclude that strain NBT06E8T represents a novel species of the genus

Halomonas

, for which the name Halomonas piezotolerans sp. nov. is proposed (type strain NBT06E8T= MCCC 1K04228T=KCTC 72680T).
A common gene drive language eases regulatory process and eco-evolutionary extensions
Authors: Verma Prateek , Reeves R. Guy , Gokhale Chaitanya S.
Published: March 2020

Synthetic gene drive technologies aim to spread transgenic constructs into wild populations even when they impose organismal fitness disadvantages. The extraordinary diversity of plausible drive mechanisms and the range of selective parameters they may encounter makes it very difficult to convey their relative predicted properties, particularly where multiple approaches are combined. The sheer number of published manuscripts in this field, experimental and theoretical, the numerous techniques resulting in an explosion in the gene drive vocabulary hinder the regulators’ point of view. We address this concern by defining a simplified parameter based language of synthetic drives. Employing the classical population dynamics approach, we show that different drive construct (replacement) mechanisms can be condensed and evaluated on an equal footing even where they incorporate multiple replacement drives approaches. Using a common language, it is then possible to compare various model properties, a task desired by regulators and policymakers. The generalization allows us to extend the study of the invasion dynamics of replacement drives analytically and, in a spatial setting, the resilience of the released drive constructs. The derived framework is available as a standalone tool. Besides comparing available drive constructs, our tool is also useful for educational purpose. Users can also explore the evolutionary dynamics of future hypothetical combination drive scenarios. Thus, our results appraise the properties and robustness of drives and provide an intuitive and objective way for risk assessment, informing policies, and enhancing public engagement with proposed and future gene drive approaches.
Integrated role of microRNA-30e-5p through targeting negative regulators of innate immune pathways during HBV infection and SLE
Authors: Mishra Richa , Bhattacharya Sanjana , Rawat Bhupendra S , Kumar Ashish , Kumar Akhilesh , Niraj Kavita , Chande Ajit , Gandhi Puneet , Khetan Dheeraj , Aggarwal Amita , Sato Seiichi , Tailor Prafullakumar , Takaoka Akinori , Kumar Himanshu
Published: March 2020

Precise regulation of innate immunity is crucial for the development of appropriate host immunity against microbial infections and the maintenance of immune homeostasis. The microRNAs are small non-coding RNA, post-transcriptional regulator of multiple genes and act as a rheostat for protein expression. Here, we identified microRNA(miR)-30e-5p (miR-30e) induced by the hepatitis B virus (HBV) and other viruses that act as a master regulator for innate immune responses. Moreover, pegylated type I interferons treatment to HBV patients for viral reduction also reduces the miRNA. Additionally, we have also shown the immuno-pathological effects of miR-30e in systemic lupus erythematous (SLE) patients and SLE mouse model. Mechanistically, the miR-30e targets multiple negative regulators namelyTRIM38, TANK, ATG5, ATG12, BECN1, SOCS1, SOCS3of innate immune signaling pathways and enhances innate immune responses. Furthermore, sequestering of endogenous miR-30e in PBMCs of SLE patients and SLE mouse model respectively by the introduction of antagomir and locked nucleic acid based inhibitor significantly reduces type I interferon and pro-inflammatory cytokines. Collectively, our study demonstrates the novel role of miR-30e in innate immunity and its prognostic and therapeutic potential in infectious and autoimmune diseases.
Dynamics of Gut Microbiome, IgA Response and Plasma Metabolome in Development of Pediatric Celiac Disease
Authors: Girdhar Khyati , Huang Qian , Dogru Yusuf Dogus , Yang Yi , Tolstikov Vladimir , Chrudinova Martina , Raisingani Amol , Ludvigsson Jonas F. , Kiebish Michael A. , Palm Noah W. , Ludvigsson Johnny , Altindis Emrah
Published: March 2020

Celiac disease (CD) is an autoimmune disorder triggered by gluten consumption. To identify the role of gut microbes in CD onset, we performed a longitudinal study focusing on two important phases of gut microbiota development at ages 2.5 and 5 (n=16). We obtained samples from children who developed CD during or after the study (CD progressors) and age, sex, and HLA-matched healthy controls. CD progressors had a distinct gut microbiota composition and IgA-sequencing identified unique IgA targets in the gut. Three cytokines, one chemokine, and 19 plasma metabolites were significantly altered in CD progressors at age 5. Feeding C57BL/6J mice with taurodeoxycholic acid (TDCA), a 2-fold increased microbiota-derived metabolite in CD progressors, caused villous atrophy, increased intraepithelial lymphocytes (IELs), CD4+ T-cells, Natural Killer cells, and Qa-1 expression on T-cells while decreasing T-regulatory cells in IELs. Thus, TDCA drives inflammation in the small intestines that potentially contribute to the CD onset.

Highlights

CD progressors have a distinct gut microbiome composition compared to healthy controls in two important phases of gut microbiota development (age 2.5 and 5 years)

CD progressors have more IgA-coated bacteria in their gut at age 5 compared to healthy controls. Further, IgA-sequencing identified unique bacterial targets in CD progressors.

Three plasma proinflammatory cytokines and a chemokine were increased in CD progressors years before diagnosis, indicating an early inflammatory response.

We identified 19 metabolites that are significantly altered in CD progress at age 5 and microbiota-derived TDCA increased two-fold.

TDCA treatment in B6 mice increased CD4+ cells and NK cells while decreasing CD8+ T-regulatory (Treg) cells. It also increased Qa-1 expression on immune cells.
Systematic Review of the Registered Clinical Trials of Coronavirus Disease 2019 (COVID-19)
Authors: Zhu Rui-fang , Gao Yu-lu , Robert Sue-Ho , Gao Jin-ping , Yang Shi-gui , Zhu Chang-tai
Published: March 2020

Background

Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have immediately carried out clinical research scheme of the COVID-19. But, there is still a lack of systematic review of registered clinical trials. Therefore, we conducted a systematic review of the clinical trials of COVID-19 to summarize the characteristics of the COVID-19 registered clinical trials.

Methods

This study is based on the recommendations of the PRISMA in the Cochrane handbook. The databases from the Chinese Clinical Registration Center and the ClinicalTrials.gov were searched to collect the registered clinical trials of COVID-19. The retrieval inception date is February 9, 2020. Two researchers independently selected the literature based on inclusion and exclusion criteria, extracted data and evaluated the risk of bias.

Results

A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) of COVID-19 were obtained. A majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials had been completed; 34 trials were early clinical exploratory trials or in a pre-experiment stage, 15 trials belonged to phrase III and 4 trials were phrase IV. The methods of intervention included traditional Chinese medicine involving 26 trials, Western medicine involving 30 trials, and integrated traditional Chinese medicine and Western medicine involving 19 trials. The subjects were mainly non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60 - 200), and the median execute time of the trials was 179 d (IQR: 94 - 366 d). The main outcomes were clinical observation and examinations. Overall, both the methodology quality of interventional trials and observational studies were low.

Conclusions

Disorderly and intensive clinical trials of COVID-19 using traditional Chinese medicine and western medicine are ongoing or will being carried out in China. However, based on the low methodology quality and small sample size and long studies execute time, we will not be able to obtain reliable, high-quality clinical evidence about COVID-19 treatment in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for the clinical trials of COVID-19 in China.
Mediator-Microorganism Interaction in Microbial Solar Cell: a Fluo-Electrochemical Insight
Authors: Beauzamy Léna , Delacotte Jérôme , Bailleul Benjamin , Tanaka Kenya , Nakanishi Shuji , Wollman Francis-André , Lemaître Frédéric
Published: March 2020

Microbial solar cells that mainly rely on the use of photosynthesic organisms are a promising alternative to photovoltaics for solar electricity production. In that way, we propose a new approach involving electrochemistry and fluorescence techniques. The coupled set-up Electro-Pulse-Amplitude-Modulation (“e-PAM”) enables the simultaneous recording of the produced photocurrent and fluorescence signals from the photosynthetic chain. This methodology was validated with a suspension of green algaChlamydomonas reinhardtiiin interaction with an exogenous redox mediatior (2,6-dichlorobenzoquinone; DCBQ). The balance between photosynthetic chain events (PSII photochemical yield, quenching) and the extracted electricity can be monitored overtime. More particularly, the non photochemical quenching induced by DCBQ mirrors the photocurrent. This set-up thus helps to distinguish the electron harvesting from some side effects due to quinones in real time. It therefore paves the way for future analyses devoted to the choice of the experimental conditions (redox mediator, photosynthetic organisms…) to find the best electron extraction.
Management implications based on diversity patterns under climate change scenarios in a continental island biodiversity hotspot
Authors: Kougioumoutzis Konstantinos , Kokkoris Ioannis P. , Panitsa Maria , Trigas Panayiotis , Strid Arne , Dimopoulos Panayotis
Published: March 2020

In the Anthropocene era, climate change poses a great challenge in environmental management and decision-making for species and habitat conservation. To support decision-making, many studies exist regarding the expected vegetation changes and the impacts of climate change on European plants, yet none has investigated how climate change will affect the extinction risk of the entire endemic flora of an island biodiversity hotspot, with intense human disturbance. Our aim is to assess, in an integrated manner, the impact of climate change on the biodiversity and biogeographical patterns of Crete and to provide a case-study upon which a cost-effective and climate-smart conservation planning strategy might be set. We employed a variety of macroecological analyses and estimated the current and future biodiversity, conservation and extinction hotspots in Crete, as well as the factors that may have shaped these distribution patterns. We also evaluated the effectiveness of climate refugia and the NATURA 2000 network (PAs) on protecting the most vulnerable species and identified the taxa that should be of conservation priority based on the Evolutionary Distinct and Globally Endangered (EDGE) index, during any environmental management process. The highlands of Cretan mountain massifs have served as both diversity cradles and museums, due to their stable climate and high topographical heterogeneity. They are also identified as biodiversity hotspots, as well as areas of high conservation and evolutionary value, due their high EDGE scores. Due to the ‘escalator to extinction’ phenomenon and the subsequent biotic homogenization, these areas are projected to become diversity ‘death-zones’ in the near future and should thus be prioritized in terms of conservation efforts and by decision makers. In-situ conservation focusing at micro-reserves and ex-situ conservation practices should be considered as an insurance policy against such biodiversity losses, which constitute cost-effective conservation measures. Scientists and authorities should aim the conservation effort at areas with overlaps among PAs and climate refugia, characterized by high diversity and EDGE scores. These areas may constitute Anthropocene refugia. Thus, this climate-smart, cost-effective conservation-prioritization planning will allow the preservation of evolutionary heritage, trait diversity and future services for human well-being and acts as a pilot for similar regions worldwide.
Resting state fluctuations underlie free and creative verbal behaviors in the human brain
Authors: Broday-Dvir Rotem , Malach Rafael
Published: March 2020

Internally generated (free) ideas and creative thoughts constitute a fundamentally important aspect of the human experience, yet the neuronal mechanism driving these behaviors remains elusive. Here we examined the hypothesis that the common mechanism underlying free verbal behaviors is the ultra-slow activity fluctuations (termed “resting state fluctuations”) that emerge spontaneously in the human brain. In our experiment, participants were asked to perform three voluntary verbal tasks: a verbal fluency task, a verbal creativity task (alternative uses of everyday objects) and a divergent thinking task (instances of common concepts), during fMRI scanning. BOLD-activity during these tasks was contrasted with a control-deterministic verbal task, in which the behavior was fully determined by external stimuli. Our results reveal that in all three voluntary tasks, the verbal-generation responses displayed a gradual anticipatory buildup that preceded the deterministic control-related responses by ∼2 seconds. Importantly, variance analysis ruled out a time-jittered step-function response confound. Critically, the waveforms of the anticipatory buildups, as reflected in their time-frequency dynamics, were significantly correlated to the dynamics of resting state fluctuations, measured during a rest period prior to the tasks. Specifically, the amplitude of low frequency fluctuations (fALFF) of the resting state time-course and the voluntary verbal responses in the left inferior frontal gyrus (LH IFG), a central hub engaged in these tasks, were correlated across individual participants. This correlation was not a general BOLD-related or verbal-response related result, as it was not found during the externally-determined verbal control condition. Furthermore, it was specific to brain regions known to be involved in language production. These results indicate that the slow buildup preceding voluntary behaviors is linked to resting state fluctuations. Thus, these ubiquitous brain fluctuations may constitute a common neural mechanism underlying the generation of free and creative behaviors in the human brain.
Natural variation in growth and physiology under salt stress in rice: QTL mapping in aHorkuch×IR29mapping population at seedling and reproductive stages
Authors: Haque Taslima , Elias Sabrina M , Razzaque Samsad , Biswas Sudip , Khan Sumaiya Farah , Azad Jewel G.M. Nurnabi , Rahman Md. Sazzadur , Juenger Thomas E. , Seraj Zeba I
Published: March 2020

Salinity has a significant negative impact on production of rice. To cope with the increased soil salinity due to climate change, we need to develop salt tolerant rice varieties that can maintain their high yield. Rice landraces indigenous to coastal Bangladesh can be a great resource to study the genetic basis of salt adaptation. In this study, we implemented a QTL analysis framework on a reciprocal mapping population between a salt tolerant landraceHorkuchand a high yieldingrice varietyIR29. Our aim was to detect genetic loci that contributes to the salt adaptive responses of the two different developmental stages of rice which are very sensitive to salinity stress. We identified 14 QTL for 9 traits and found that most are unique to the specific developmental stage. In addition, we detected a significant effect of the cytoplasmic genome on the QTL model for some traits such as leaf total potassium and filled grain weight. This underscores the importance of considering cytoplasm-nuclear interaction for breeding programs. Along with this, we identified QTL co-localization for multiple traits that highlights the possible constraint of multiple QTL selection for breeding programs due to different contributions of a donor allele for different traits.

Highlights

We identified genetic loci for the salt tolerance response of two different developmental stages of the rice plant and detected significant contribution of cytoplasm-nuclear genome interaction for a few traits.
The Vpu-interacting protein ATP6V0C regulates expression of tetherin and HIV-1 release
Authors: Waheed Abdul A. , Swiderski Maya , Khan Ali , Gitzen Ariana , Majadly Ahlam , Freed Eric O.
Published: March 2020

The HIV-1 accessory protein Vpu enhances virus release by down-regulating cell surface expression of the host restriction factor tetherin. To further understand the role of host proteins in Vpu function, we carried out yeast two-hybrid screening and identified the V0 subunit C of vacuolar ATPase (ATP6V0C) as a Vpu-binding protein. To examine the role of ATP6V0C in Vpu-mediated tetherin degradation and HIV-1 release, we knocked down ATP6V0C expression in HeLa cells and observed that ATP6V0C depletion impairs Vpu-mediated tetherin degradation, resulting in a defect in HIV-1 release. We also observed that overexpression of ATP6V0C stabilizes tetherin expression. This stabilization is specific to ATP6V0C, as overexpression of another subunit of the vacuolar ATPase, ATP6V0C”, had no effect on tetherin expression. ATP6V0C overexpression did not stabilize CD4, another target of Vpu-mediated degradation. Immunofluorescence localization studies showed that the ATP6V0C-stabilized tetherin is sequestered in a CD63- and LAMP1-positive intracellular compartment. These data demonstrate that the Vpu-interacting protein ATP6V0C plays a role in regulating tetherin expression and HIV-1 assembly and release.
Resolving widespread incomplete and uneven archaeal classifications based on a rank-normalized genome-based taxonomy
Authors: Rinke Christian , Chuvochina Maria , Mussig Aaron J. , Chaumeil Pierre-Alain , Davin Adrian A. , Waite David W. , Whitman William B , Parks Donovan H. , Hugenholtz Philip
Published: March 2020

An increasing wealth of genomic data from cultured and uncultured microorganisms provides the opportunity to develop a systematic taxonomy based on evolutionary relationships. Here we propose a standardized archaeal taxonomy, as part of the Genome Taxonomy Database (GTDB), derived from a 122 concatenated protein phylogeny that resolves polyphyletic groups and normalizes ranks based on relative evolutionary divergence (RED). The resulting archaeal taxonomy is stable under a range of phylogenetic variables, including marker genes, inference methods, corrections for rate heterogeneity and compositional bias, tree rooting scenarios, and expansion of the genome database. Rank normalization was shown to robustly correct for substitution rates varying up to 30-fold using simulated datasets. Taxonomic curation follows the rules of the International Code of Nomenclature of Prokaryotes (ICNP) while taking into account proposals to formally recognise the rank of phylum and to use genome sequences as type material. The taxonomy is based on 2,392 quality screened archaeal genomes, the great majority of which (93.3%) required one or more changes to their existing taxonomy, mostly as a result of incomplete classification. In total, 16 archaeal phyla are described, including reclassification of three major monophyletic units from the former Euryarchaeota and one phylum resulting from uniting the TACK superphylum into a single phylum. The taxonomy is publicly available at the GTDB website (https://gtdb.ecogenomic.org).
Clinical Characteristics of Patients with Severe Pneumonia Caused by the 2019 Novel Coronavirus in Wuhan, China
Authors: Wang Yafei , Zhou Ying , Yang Zhen , Xia Dongping , Geng Shuang
Published: March 2020

Background

A new virus broke out in Wuhan, Hubei, China, and was later named 2019 novel coronavirus (2019-nCoV). The clinical characteristics of severe pneumonia caused by 2019-nCoV are still not clear.

Objectives

The aim of this study was to explore the clinical characteristics and risk factors of the severe pneumonia caused by the 2019-nCoV in Wuhan, China.

Method

The study included patients hospitalized at the central hospital of Wuhan who had been diagnosed with a pneumonia caused by the novel coronavirus. Clinical features, chronic co-morbidities, demographic data, laboratory examinations, and chest computed tomography (CT) scans were reviewed through electronic medical records. SPSS was used for data analysis to explore the clinical characteristics and risk factors of the patients with the severe pneumonia.

Results

A total of 110 patients diagnosed with 2019 novel coronavirus pneumonia were included in the study, including 38 with severe pneumonia and 72 with non-severe pneumonia. Statistical analysis showed that advanced age, an increase of D-dimer, and a decrease of lymphocytes were characteristics of the patients with severe pneumonia. Moreover, in the early stage of the disease, chest CT scans of patients with the severe pneumonia showed the illness can progress rapidly.

Conclusions

Advanced age, lymphocyte decline, and D-dimer elevation are important characteristics of patients with severe pneumonia. Clinicians should focus on these characteristics to identify high-risk patients at an early stage.
Animal personality adds complexity to the processes of adaptive divergence and speciation
Authors: Horta-Lacueva Quentin J.B. , Benhaïm David , Morrissey Michael B. , Snorrason Sigurður S. , Kapralova Kalina H.
Published: March 2020

Divergent selection is a powerful driver of speciation and has been widely studied in relation to the physical characters of organisms. Because evolution of behavioural traits may contribute to evolutionary processes, we explored how consistent variation in behaviours may affect the process of adaptive divergence and speciation. We studied whether two sympatric morphs of Arctic charr (Salvelinus alpinus) have recently evolved genetically-based differences in personality that conform to their respective ecological niches, and whether these differences contribute to reproductive isolation by generating maladaptive hybrid behaviours. Studying three aspects of behavioural variation (average trait value, consistent individual differences and trait covariance), we assessed the sociality and risk-taking propensity of hybrid and pure-morph offspring reared in common conditions. Contrary to expectations, the two morphs did not differ in the average values of these traits but showed different behavioural syndromes (trait covariances). While the hybrids did not differ from either morph in their average behavioural responses, they showed less individual consistency in these behaviours and a different set of behavioural syndromes. Differences between morphs and their hybrids in other behavioural aspects than their average behavioural responses suggest that our understanding of speciation processes can benefit from an integrative view of behavioural variation.
Microbiological water quality of Managed Aquifer Recharge systems in the salinity-prone southwest coastal Bangladesh
Authors: Doza Solaiman , Naser Abu Mohd , Rahman Md Mahbubur , Mondol Momenul Haque , Khan Golam Kibria , Uddin Md. Nasir , Gazi Mohammed Shahid , Alam Gazi Raisul , Karim Mohammed Rabiul , Ahmed Kazi Matin , Luby Stephen P. , Clasen Thomas , Unicomb Leanne
Published: March 2020

Managed aquifer recharge (MAR), a hydro-geological intervention designed to dilute groundwater salinity, pumps pond water treated through a slow sand filter into the underground aquifers. We evaluated the microbiological safety of the resulting MAR water at sites from three districts in southwest coastal Bangladesh. We collected monthly paired pond-MAR water samples from July 2016-June 2017 and enumerated fecal coliforms andE. coliusing the IDEXX quanti-tray technique, by the most probable number (MPN) method. We used WHO risk categories for microbiological quality; no risk (<1 MPN), low risk (1-10 MPN) and moderate to high risk (>10 MPN per 100 mL water). We estimated the difference in mean log10MPN in pond and MAR water using linear mixed effect models with random intercepts and cluster adjusted robust standard error. Almost all pond water samples (292/299, 98%) had moderate- to high-risk level (>10 MPN) fecal coliforms andE. coli(283/299, 95%). In contrast, 81% (242/300) of MAR water samples had no or low risk level fecal coliforms (0-10 MPN), of which 60% (179/300) had no fecal coliforms. We detected no or low risk levelE. coliin 94% (283/300) of MAR water samples of these 80% (240/300) had noE. coli.MAR samples had lower mean log10MPN fecal coliforms (-2.37; 95% CI: -2.56, -2.19) andE. coli(-2.26; 95% CI: - 2.43, -2.09) than pond water; microbial reductions remained consistent during the wet (May-October) and dry seasons. MAR-systems provided water with reduced fecal indicator bacteria compared to infiltered pond water.
Uncovering microbial populations in the lumen of neonatal enteral feeding tubes utilising 16s rRNA sequencing
Authors: Winnard Christopher J , Green Sue , Baylay Alison , Johnson Mark J , Fader Mandy , Keevil Charles W , Wilks Sandra
Published: March 2020

Gastrointestinal microbiome is increasingly implicated in the morbidity associated with being born preterm. Enteral tubes (ET) are essential for the nutritional care of preterm infants. Limited culture-based studies have suggested they are colonised by high densities of microorganisms. Microbial DNA was extracted from 60 ETs retrieved from infants in a tertiary neonatal unit and analysed by16s rRNA sequencing of the V4 variable region. Relative abundance analysis on dominant microorganisms demonstrated that compared to breast milk, formula significantly increased abundance ofStreptococcus sppand significantly decreasedEnterococcus sppand Enterobacteriaceae Vaginal birth was also associated with significantly increased relative abundance ofStreptococcus. This study more accurately demonstrates the extent of microbial diversity in neonatal ETs, with feeding regime significantly influencing colonisation patterns. Colonisation with unwanted organisms, as a result of specific care regimes, could result in disruption of the fragile infant gut microbiome, with implications for long-term morbidity.
Stress induces the transcription of toxin-antitoxin systems but does not activate toxin
Authors: LeRoux Michele , Culviner Peter H. , Liu Yue J. , Littlehale Megan L. , Laub Michael T.
Published: March 2020

Toxin-antitoxin (TA) systems are ubiquitous genetic elements in bacterial genomes, but their functions are controversial. Although they are frequently postulated to regulate cell growth following stress, few null phenotypes for TA systems have been reported. Here, we show that TA transcript levels can increase substantially in response to stress, but toxin is not liberated. We find that the growth of anEscherichia colistrain lacking 10 TA systems encoding endoribonuclease toxins is not affected following exposure to six stresses that each trigger TA transcription. Additionally, using RNA-sequencing, we find no evidence of mRNA cleavage following stress. Stress-induced transcription arises from antitoxin degradation and relief of transcriptional autoregulation. Importantly, although free antitoxin is readily degradedin vivo, antitoxin bound to toxin is protected from proteolysis, preventing release of active toxin. Thus, transcription is not a reliable marker of TA activity, and TA systems likely do not strongly promote survival following stress.
A new role for histone demethylases in the maintenance of plant genome integrity
Authors: Antunez-Sanchez Javier , Naish Matthew , Ramirez-Prado Juan Sebastian , Ohno Sho , Huang Ying , Dawson Alexander , Manza-Mianza Deborah , Ariel Federico , Raynaud Cecile , Wilbowo Anjar , Daron Josquin , Ueda Minako , Latrasse David , Slotkin R. Keith , Weigel Detlef , Benhamed Moussa , Gutierrez-Marcos Jose
Published: March 2020

Histone modifications deposited by the Polycomb repressive complex 2 (PRC2) play a critical role in the control of growth, development and adaptation to environmental fluctuations in most multicellular eukaryotes. The catalytic activity of PRC2 is counteracted by Jumonji-type (JMJ) histone demethylases, which shapes the genomic distribution of H3K27me3. Here, we show that two JMJ histone demethylases in Arabidopsis, EARLY FLOWERING 6 (ELF6) and RELATIVE OF EARLY FLOWERING 6 (REF6), play distinct roles in H3K27me3 and H3K27me1 homeostasis. We show that failure to reset these chromatin marks during sexual reproduction results in the inheritance of epigenetic imprints, which cause a loss of DNA methylation at heterochromatic loci and transposon activation. Thus, Jumonji-type histone demethylases in plants contribute towards maintaining distinct transcriptional states during development and help safeguard genome integrity following sexual reproduction.
Defining totipotency using criteria of increasing stringency
Authors: Posfai Eszter , Schell John Paul , Janiszewski Adrian , Rovic Isidora , Murray Alexander , Bradshaw Brian , Pardon Tine , El Bakkali Mouna , Talon Irene , De Geest Natalie , Kumar Pankaj , To San Kit , Petropoulos Sophie , Jurisicova Andrea , Pasque Vincent , Lanner Fredrik , Rossant Janet
Published: March 2020

Totipotency is the ability of a single cell to give rise to all the differentiated cells that build the conceptus, yet how to capture this propertyin vitroremains incompletely understood. Defining totipotency relies upon a variety of assays of variable stringency. Here we describe criteria to define totipotency. We illustrate how distinct criteria of increasing stringency can be used to judge totipotency by evaluating candidate totipotent cell types in the mouse, including early blastomeres and expanded or extended pluripotent stem cells. Our data challenge the notion that expanded or extended pluripotent states harbor increased totipotent potential relative to conventional embryonic stem cells underin vivoconditions.