bluuebunny/crossref_metadata_2025 huggingface dataset:
Myosin V regulates spatial localization of different forms of neurotransmitter release in central synapses
Authors: Maschi Dario , Gramlich Michael W. , Klyachko Vitaly A.
Published: December 2020

Synaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicluar (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites (Maschi et al, 2018). Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center towards periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition of myosin V also reduces preferential utilization of central release sites during MVR, leading to more spatially distributed and temporally uniform MVR that occurs farther away from the AZ center. Thus myosin V regulates both temporal and spatial utilization of release sites during two main forms of synchronous release.
Waterbird abundance and diversity along a stretch of Ganga River, India modified by construction of a barrage
Authors: Vasudeva Vaishali , Garg J.K. , Badola Ruchi , Hussain Syed Ainul
Published: December 2020

Damming and diverting river water alters the channel characteristics and natural flow regime. The change in biotic and abiotic factors results in dissimilar habitat conditions upstream and downstream of the barrage. Given the habitat dissimilarity and therefore resource availability, we hypothesized the dissimilarity in waterbird abundance and species diversity in the river habitat upstream and downstream of the barrage. The study was conducted on a 24 km stretch of Ganga River at Narora, Uttar Pradesh, India. This stretch overlaps with a Ramsar site as well as an Important Bird and Biodiversity Area (IBA). Bird sampling was done using transect count method for summer and winter season in 2017. The abundance was studied in relation to three habitat variablesviz. channel depth, channel width and anthropogenic disturbances using Generalized Linear Model. A total of 140 species of birds were recorded. There was statistically significant difference in the abundance of waterbirds between upstream and downstream stretch in winter season (Mann-Whitney U,p< 0.05). During winters, migratory waterbirds especially ducks and geese occupied the deep water upstream of barrage, while the downstream was mostly occupied by terns and cormorants. Waterbird species diversity was higher in downstream during winters (Effective Number of Species=28; Shannon’s Index= 3.35) and higher in upstream during summer (Effective Number of Species=25, Shannon’s Index=2.87). Channel width, channel depth and anthropogenic disturbance influenced waterbird abundance in both the seasons (Generalized Linear Model;p< 0.05). The influence of channel depth varied with season for the upstream stretch.
Existence and Features of the Myodural Bridge in Gentoo Penguins: a morphological study
Authors: Chen Cheng , Yu Sheng-bo , Chi Yan-yan , Tan Guang-yuan , Yan Bao-cheng , Zheng Nan , Sui Hong-Jin
Published: December 2020

Recent studies have evidenced that the anatomical structure now known as the myodural bridge (MDB) connects the suboccipital musculature to the cervical spinal dura mater (SDM). In humans, the MDB passes through both the posterior atlanto-occipital and the posterior atlanto-axial interspaces. The present authors suggest that the MDB has important physiological functions in humans. The existence of the MDB in various mammals, including flying birds (Rock pigeons and Gallus domesticus) has been previously validated. Gentoo penguins are marine birds, able to make 450 dives per day, reaching depths of up to 660 feet. Gentoo penguins are also the world’s fastest diving birds. The present study was therefore carried out to investigate the existence and characteristics of the MDB in Gentoo penguin (Pygoscelis papua), a non-flying, marine bird that can dive. While foraging, this penguin is able to reach speeds of up to 22 miles per hour. For this study, six Gentoo penguin specimens were dissected to observe the existence and composition of their MDB. Histological staining was also performed to analyze the anatomic relationships and characteristic of the MDB in the Gentoo penguin. In this study, it was found that the suboccipital musculature in the Gentoo penguin consists of the rectus capitis dorsalis minor (RCDmi) muscle and rectus capitis dorsalis major (RCDma) muscle. Dense connective tissue fibers were observed connecting these two suboccipital muscles to the spinal dura mater (SDM). This dense connective tissue bridge consists of primarily type I collagen fibers. Thus, this penguin’s MDB appears to be analogous to the MDB previously observed in humans. The present study evidences that the MDB not only exists in penguins but it also has unique features that distinguishes it from that of flying birds. Thus, this study advances the understanding of the morphological characteristics of the MDB in flightless, marine birds.
Evaluation of the tyrosine and dopamine serum level in experimental infected BALB/c mice with chronic toxoplasmosis
Authors: Mirzaeipour Mehdi , Mikaeili Fattaneh , Asgari Qasem , Nohtani Mohammad , Rashidi Sajad , Bahreini Mohammad Saleh
Published: December 2020

Background

Toxoplasmaparasite alters the transduction of neurotransmitter signals and leads to changes in the level of brain neurotransmitters including tyrosine and dopamine, so, behavior changes can occur in infected hosts. Based on this concept, this study was conducted for evaluation of the tyrosine and dopamine serum level in infected mice with chronic toxoplasmosis.

Materials and methods

Toxoplasma gondii(Prugniaud strain II) was injected intra-peritoneal into BALB/c mice to induce chronic toxoplasmosis. Modified agglutination test (MAT), polymerase chain reaction (PCR), and microscopic methods were conducted to confirm the induction of chronic toxoplasmosis. The infected mice sera were separated at days 40, 50, 60, 70, and 80 for evaluation of tyrosine and dopamine serum level using High-performance Liquid Chromatography (HPLC).

Results

Microscopic methods confirmed the formation of theToxoplasmacysts in mice tissues. Inducing chronic toxoplasmosis is also confirmed by MAT, PCR and histological methods. HPLC results indicated a decrease in serum tyrosine level at days 40 in infected mice in comparison to control and the levels were too low to be measured at other times. However, a significantly high serum dopamine level was observed that gradually increased after parasite inoculation.

Conclusions

No detection of tyrosine level in most of the sample groups is probably related to the very low concentration of tyrosine in sera. However, low concentration of tyrosine at days 40 and increase of dopamine in most of the sample groups suggests the production of dopamine from tyrosine due to the presence ofToxoplasmain infected mice.
Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for dynamic inter-molecular interactions involved in viral genome replication
Authors: Loundras Eleni-Anna , Streetley James , Herod Morgan R. , Thompson Rebecca F. , Harris Mark , Bhella David , Stonehouse Nicola J.
Published: December 2020

Replication of many positive-sense RNA viruses occurs within intracellular membrane-associated compartments. These are believed to provide a favourable environment for replication to occur, concentrating essential viral structural and non-structural components, as well as protecting these components from host-cell pathogen recognition and innate immune responses. However, the details of the molecular interactions and dynamics within these structures is very limited. One of the key components of the replication machinery is the RNA-dependent RNA polymerase, RdRp. This enzyme has been shown to form higher-order fibrilsin vitro. Here, using the RdRp from foot-and-mouth disease virus (termed 3Dpol), we report fibril structures, solved at ~7-9 Å resolution by cryo-EM, revealing multiple conformations of a flexible assembly. Fitting high-resolution coordinates led to the definition of potential intermolecular interactions. We employed mutagenesis using a sub-genomic replicon system to probe the importance of these interactions for replication. We use these data to propose models for the role of higher order 3Dpolcomplexes as a dynamic scaffold within which RNA replication can occur.
NetGenes: A database of essential genes predicted using features from interaction networks
Authors: Senthamizhan Vimaladhasan , Ravindran Balaraman , Raman Karthik
Published: December 2020

Essential gene prediction models built so far are heavily reliant on sequence-based features and the scope of network-based features has been narrow. Previous work from our group demonstrated the importance of using network-based features for predicting essential genes with high accuracy. Here, we applied our approach for the prediction of essential genes to organisms from the STRING database and hosted the results in a standalone website. Our database, NetGenes, contains essential gene predictions for 2700+ bacteria predicted using features derived from STRING protein-protein functional association networks. Housing a total of 3.5M+ genes, NetGenes offers various features like essentiality scores, annotations and feature vectors for each gene. NetGenes is available athttps://rbc-dsai-iitm.github.io/NetGenes/
Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: a Longitudinal Study in a Macaque Model of Parkinson’s Disease
Authors: Wianny Florence , Dzahini Kwamivi , Fifel Karim , Wilson Charles R.E. , Bernat Agnieszka , Dolmazon Virginie , Misery Pierre , Lamy Camille , Cooper Howard M. , Procyk Emmanuel , Kennedy Henry , Savatier Pierre , Dehay Colette , Vezoli Julien
Published: December 2020

Parkinson’s disease (PD) evolves over an extended and variable period in humans; several years prior to the onset of classical motor symptoms, cognitive deficits as well as sleep and biological rhythm disorders develop and worsen with disease progression, significantly impacting the quality of life of patients. The gold standard MPTP macaque model of PD recapitulates the progression of motor and non-motor symptoms over contracted periods of time.

Here, this multidisciplinary and multiparametric study follows, in five animals, the steady progression of motor and non-motor symptoms and describes their reversal following bilateral grafts of neural precursors in diverse functional domains of the basal ganglia.

Results show unprecedented recovery from cognitive symptoms in addition to a strong clinical motor recuperation. Both motor and cognitive recovery and partial circadian rhythm recovery correlate with the degree of graft integration into the host environment as well as with in-vivo levels of striatal dopaminergic innervation and function.

Given inter-individuality of disease progression and recovery the present study underlines the importance of longitudinal multidisciplinary assessments in view of clinical translation and provides empirical evidence that integration of neural precursors following transplantation efficiently restores function at multiple levels in parkinsonian non-human primates.

One Sentence Summary

Empirical evidence that cell therapy efficiently reverts cognitive and clinical motor symptoms in the non-human primate model of Parkinson’s disease.
A human coronavirus evolves antigenically to escape antibody immunity
Authors: Eguia Rachel , Crawford Katharine H. D. , Stevens-Ayers Terry , Kelnhofer-Millevolte Laurel , Greninger Alexander L. , Englund Janet A. , Boeckh Michael J. , Bloom Jesse D.
Published: December 2020

There is intense interest in antibody immunity to coronaviruses. However, it is unknown if coronaviruses evolve to escape such immunity, and if so, how rapidly. Here we address this question by characterizing the historical evolution of human coronavirus 229E. We identify human sera from the 1980s and 1990s that have neutralizing titers against contemporaneous 229E that are comparable to the anti-SARS-CoV-2 titers induced by SARS-CoV-2 infection or vaccination. We test these sera against 229E strains isolated after sera collection, and find that neutralizing titers are lower against these “future” viruses. In some cases, sera that neutralize contemporaneous 229E viral strains with titers >1:100 do not detectably neutralize strains isolated 8–17 years later. The decreased neutralization of “future” viruses is due to antigenic evolution of the viral spike, especially in the receptor-binding domain. If these results extrapolate to other coronaviruses, then it may be advisable to periodically update SARS-CoV-2 vaccines.
Co-opting regulation bypass repair (CRBR) as a gene correction strategy for monogenic diseases
Authors: Hu Jingjie , Bourne Rebecca A. , McGrath Barbara C. , Lin Alice , Pei Zifei , Cavener Douglas R.
Published: December 2020

With the development of CRISPR/Cas9-mediated gene editing technologies, correction of disease- causing mutations has become possible. However, current gene correction strategies preclude mutation repair in post-mitotic cells of human tissues, and a unique repair strategy must be designed and tested for each and every mutation that may occur in a gene. We have developed a novel gene correction strategy, Co-opting Regulation Bypass Repair (CRBR), which can repair a spectrum of mutations in mitotic or post-mitotic cells and tissues. CRBR utilizes the non-homologous end-joining (NHEJ) pathway to insert a coding sequence (CDS) and transcription/translation terminators targeted upstream of any CDS mutation and downstream of the transcriptional promoter. CRBR gene repair results in simultaneous co-option of the endogenous regulatory region and bypass of the genetic defect. We demonstrated the potential of CRBR strategy for human gene therapy by rescuing a mouse model of the Wolcott-Rallison syndrome (WRS) with permanent neonatal diabetes caused by either large deletion or nonsense mutation in the PERK (EIF2AK3) gene. Additionally, we expressed a GFP CDS-terminator cassette that was integrated downstream of the human insulin promoter in cadaver pancreatic islets of Langerhans which paves the way for autologous cell-tissue replacement therapy for gene repair in beta cells.
Probiotic Supplementation Reduces Inflammatory Profiles But Does Not Prevent Oral Immune Perturbations During SIV Infection
Authors: Jones Rhianna , Kroll Kyle , Broedlow Courtney , Schifanella Luca , Smith Scott , Hueber Brady , Shah Spandan V. , Ram Daniel R. , Manickam Cordelia , Varner Valerie , Klatt Nichole R. , Reeves R. Keith
Published: December 2020

HIV/SIV infections lead to massive loss of mucosal CD4+ T cells and breakdown of the epithelial mucosa resulting in severe microbial dysbiosis and chronic immune activation that ultimately drive disease progression. Moreover, disruption of one of the most understudied mucosal environments, the oral cavity, during HIV-induced immunosuppression results in significant microbial and neoplastic co-morbidities and contributes to and predicts distal disease complications. In this study we evaluated the effects of oral probiotic supplementation (Pbx), which can stimulate and augment inflammatory or anti-inflammatory pathways, on early SIV infection of rhesus macaques. Our study revealed that similar to the GI mucosae, oral CD4+ T cells were rapidly depleted, and as one of the first comprehensive analyses of the oral microflora in SIV infection, we also observed significant modulation among two genera,PorphyromonasandActinobacillus,early after infection. Interestingly, although Pbx therapy did not substantially protect against oral dysbiosis or ameliorate cell loss, it did dampen inflammation and T cell activation. Collectively, these data provide one of the most comprehensive evaluations of SIV-induced changes in oral microbiome and CD4+ T cell populations, and also suggest that oral Pbx could be a simple therapy to improve anti-inflammatory states in addition to more traditional antivirals.
Honeybee genetics shape the strain-level structure of gut microbiota in social transmission
Authors: Wu Jiaqiang , Lang Haoyu , Mu Xiaohuan , Zhang Zijing , Su Qinzhi , Hu Xiaosong , Zheng Hao
Published: December 2020

Honeybee gut microbiota transmitted via social interactions are beneficial to the host health. Although the microbial community is relatively stable, individual variations and high strain-level diversity have been detected across honeybees. Although the bee gut microbiota structure is influenced by environmental factors, the heritability of the gut members and the contribution of the host genetics remains elusive. Considering bees within a colony are not readily genetically identical due to the polyandry of queen, we hypothesize that the microbiota structure can be shaped by host genetics. We used shotgun metagenomics to simultaneously profile the microbiota and host genotypes of individuals from hives of four different subspecies. Gut composition is more distant between genetically different bees at both phylotype- and “sequence-discrete population”-level. We then performed a successive passaging experiment within colonies of hybrid bees generated by artificial insemination, which revealed that the microbial composition dramatically shifts across batches of bees during the social transmission. Specifically, different strains from the phylotype ofSnodgrassella alviare preferentially selected by genetically varied hosts, and strains from different hosts show a remarkably biased distribution of single-nucleotide polymorphism in the Type IV pili loci. A genome-wide association analysis identified that the relative abundance of a cluster ofBifidobacteriumstrains is associated with the host glutamate receptor gene that is specifically expressed in the bee brain. Finally, mono-colonization ofBifidobacteriumwith a specific polysaccharide utilization locus impacts the expression and alternative splicing of thegluR-Bgene, which is associated with an altered circulating metabolomic profile. Our results indicated that host genetics influence the bee gut composition, and suggest a gut-brain connection implicated in the gut bacterial strain preference. Honeybees have been used extensively as a model organism for social behaviors, genetics, and gut microbiome. Further identification of host genetic function as shaping force of microbial structure will advance our understanding of the host-microbe interactions.
League of Brazilian Bioinformatics: a competition framework to promote scientific training
Authors: Carvalho L. M. , Coimbra N. A. R. , Neves M. R. C. , Fonseca N. J. , Costa M. A. , Horacio E. C. A. , Riyuzo R. , Aburjaile F. F. , Nagamatsu S. T.
Published: December 2020

Background

the scientific training to become a bioinformatician includes multidisciplinary abilities, which increase the challenges to professional development.

Competition framework

in order to improve and promote the ongoing training of the Brazilian bioinformatics community, we organize a national competition, with the main goal to develop human resources and abilities in Computational Biology at the national level. The competition framework was designed in three phases: 1) a one-day challenge composed of 60 multiple-choice questions covering Biology, Computer Science, and Bioinformatics knowledge; 2) five Computational Biology challenges to be solved in three days; and 3) development of an original project evaluated during the 15th X-meeting.

Results

the first edition of the League of Brazilian Bioinformatics (LBB) counted 168 competitors and 59 groups, distributed into undergraduate students (14.4%), graduate students (12.6% master and 16.8%, Ph.D.), and other professional fields. The first phase selected 46 teams to proceed in the competition, while the second phase selected the three top-performing teams.

Conclusion

during the competition, we were able to stimulate teamwork in the main areas of Bioinformatics, with the engagement of all research-level competitors. Furthermore, we identified opportunities to deliver and offer better training to the community and we intend to apply the acquired experience in the second edition of the LBB, which will occur in 2021.

Supplementary information

Supplementary data are available atBioinformatics
Is occupational physical activity associated with all-cause mortality in UK Biobank?
Authors: Pearce Matthew , Strain Tessa , Wijndaele Katrien , Sharp Stephen J. , Mok Alexander , Brage Soren
Published: December 2020

Objectives

To investigate associations between occupational physical activity (OPA) and all-cause mortality.

Methods

From baseline (2006-2010), 452,884 UK Biobank participants (aged 40-69 years) were followed for a median 11.1 (IQR: 10.4-11.8) years. OPA was categorised by cross-tabulating degree of manual work and walking/standing work amongst those in paid employment (n=264,424), whereas categories of occupational status were used for those not in paid employment (n=188,460). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality by occupational category, and for working hours/week and non-occupational physical activity stratified by occupational category.

Results

During 4,965,616 person-years of follow-up, 23,310 deaths occurred. Compared to those in sedentary jobs, retirement was associated with lower mortality in women (HR=0.74, CI:0.68-0.81) and men (HR=0.85, CI:0.79-0.92), whereas unemployment was associated with higher mortality in men (HR=1.26, CI:1.10-1.45). There was no evidence of mortality differences by OPA category within the working population. Working <35 hours/week versus 35-40 hours/week was associated with lower mortality in both women (HR=0.86, CI:0.79-0.93) and men (HR=0.81, CI:0.75-0.88), with no interaction by OPA. Non-occupational physical activity was associated with lower mortality in both women (HR=0.90 per 5 kJ/day/kg, CI:0.84-0.96) and men (HR=0.88 per 5 kJ/day/kg, CI:0.84-0.92), with no interaction by OPA.

Conclusion

Work classified as having higher levels of OPA may not be as active as reported, or the types of physical activity performed in those jobs are not health-enhancing. Irrespective of OPA category or employment status, non-occupational physical activity appears to provide health benefits.

SUMMARY BOX

What are the new findings?

Retirement was associated with lower all-cause mortality, compared to having a sedentary job in both men and women but unemployment was only associated with higher mortality in men.

There were no differences in mortality between categories with different levels of self-reported OPA

Physical activity outside of work was associated with lower hazard of all-cause mortality and there was no interaction with occupational physical activity, indicating similar benefits across different jobs types.

How might it impact on clinical practice in the future?

Health professionals should be aware that occupations assumed to involve more physical activity may not be as active as reported, or the types of physical activity performed in those jobs may not be health-enhancing.

Physical activity during leisure-time should continue to be recommended to adults of all paid and unpaid occupational categories.
Current evidence for COVID-19 therapies: a systematic literature review
Authors: Welte Tobias , Ambrose Lucy J. , Sibbring Gillian C. , Sheikh Shehla , Müllerová Hana , Sabir Ian
Published: December 2020

Effective therapeutic interventions for the treatment and prevention of COVID-19 are urgently needed. A systematic review was conducted to identify clinical trials of pharmacological interventions for COVID-19 published between 1 December 2019 and 14 October 2020. Data regarding efficacy of interventions, in terms of mortality, hospitalisation and need for ventilation, were extracted from identified studies and synthesised qualitatively.

In total, 42 clinical trials were included. Interventions assessed included antiviral, mucolytic, anti-malarial, anti-inflammatory and immunomodulatory therapies. Some reductions in mortality, hospitalisation and need for ventilation were seen with interferons and remdesivir, particularly when administered early, and with the mucolytic drug, bromhexine. Most studies of lopinavir/ritonavir and hydroxychloroquine did not show significant efficacy over standard care/placebo. Dexamethasone significantly reduced mortality, hospitalisation and need for ventilationversusstandard care, particularly in patients with severe disease. Evidence for other classes of interventions was limited. Many trials had a moderate-to-high risk of bias, particularly in terms of blinding; most were short-term; and some included low patient numbers.

This review highlights the need for well-designed clinical trials of therapeutic interventions for COVID-19 to increase the quality of available evidence. It also emphasises the importance of tailoring interventions to disease stage and severity for maximum efficacy.
Bias Reduction through Analysis of Competing Events (BRACE): A Novel Method to Mitigate Bias from Residual Confounding in Observational Data
Authors: Mell Loren K. , Nelson Tyler , Thompson Caroline A. , Williamson Casey W. , Vitzthum Lucas K. , Zou Jingjing
Published: December 2020

Purpose

To introduce a method to mitigate bias from residual confounding in non-randomized data and examine its performance under varying conditions using simulated data.

Methods

We developed a method called Bias Reduction through Analysis of Competing Events (BRACE) based on a proportional relative hazards model. We followed recommended guidelines (ADEMP) established for the conduct of simulation studies. The primary estimand of interest was the treatment effect on the composite hazard for a primary or competing event. We compared the BRACE method to a standard Cox proportional hazards regression model in the presence of an unmeasured confounder, using a parametric (Weibull) simulation model. We examined estimator distributions, bias, mean squared error (MSE), and coverage probability for both methods using ridge, box-and-whisker, forest, and zip plots, respectively. Comparisons with a hypothetical validation estimate treating the confounder as measurable were also performed.

Results

We presented 16 simulation scenarios under varying parameters. In simulations where residual confounding was present, the BRACE method uniformly reduced both bias and MSE compared to standard Cox models. In the scenario of moderate bias with an effective but non-toxic treatment, MSE was 3.51×10−2 with the standard model vs. 0.259×10−2 with the BRACE method. In the absence of bias, the BRACE method introduced bias toward the null (2.90 x10−2) compared to the standard method (0.331×10−2), albeit with lower MSE (0.341 x10−2 vs. 0.484 x10−2, respectively). Relative to the standard approach, the BRACE method markedly improved coverage probability, but with a tendency toward overcorrection in the case of the effective but non-toxic treatment. Conclusions were similar under different parameter assumptions.

Conclusion

The BRACE method can reduce bias and MSE in the setting of residual confounding.
Improved microbial community characterization of 16S rRNA via metagenome hybridization capture enrichment
Authors: Beaudry Megan Sarah , Wang Jincheng , Kieran Troy , Thomas Jesse , Bayona-Vasquez Natalia Juliana , Gao Bei , Devault Alison , Brunelle Brian , Lu Kun , Wang Jia-Sheng , Rhodes Olin E. , Glenn Travis C.
Published: December 2020

Environmental microbial diversity is often investigated from a molecular perspective using 16S ribosomal RNA (rRNA) gene amplicons and shotgun metagenomics. While amplicon methods are fast, low-cost, and have curated reference databases, they can suffer from amplification bias and are limited in genomic scope. In contrast, shotgun metagenomic methods sample more genomic regions with fewer sequence acquisition biases. However, shotgun metagenomic sequencing is much more expensive (even with moderate sequencing depth) and computationally challenging. Here, we develop a set of 16S rRNA sequence capture baits that offer a potential middle ground with the advantages from both approaches for investigating microbial communities. These baits cover the diversity of all 16S rRNA sequences available in the Greengenes (v. 13.5) database, with no sequence having < 80% sequence similarity to at least one bait for all segments of 16S. The use of our baits provide comparable results to 16S amplicon libraries and shotgun metagenomic libraries when assigning taxonomic units from 16S sequences within the metagenomic reads. We demonstrate that 16S rRNA capture baits can be used on a range of microbial samples (i.e., mock communities and rodent fecal samples) to increase the proportion of 16S rRNA sequences (average >400-fold) and decrease analysis time to obtain consistent community assessments. Furthermore, our study reveals that bioinformatic methods used to analyze sequencing data may have a greater influence on estimates of community composition than library preparation method used, likely in part to the extent and curation of the reference databases considered.
Glycyrrhizin effectively neutralizes SARS-CoV-2 in vitro by inhibiting the viral main protease
Authors: van de Sand L. , Bormann M. , Alt M. , Schipper L. , Heilingloh C.S. , Todt D. , Dittmer U. , Elsner C. , Witzke O. , Krawczyk A.
Published: December 2020

The newly emerged coronavirus, which was designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 disease. High effective and well-tolerated medication for hospitalized and non-hospitalized patients is urgently needed. Traditional herbal medicine substances were discussed as promising candidates for the complementary treatment of viral diseases and recently suggested for the treatment of COVID-19. In the present study, we investigated aqueous licorice root extract for its neutralizing activity against SARS-CoV-2in vitro, identified the active compound glycyrrhizin and uncovered the respective mechanism of viral neutralization. We demonstrated that glycyrrhizin, the primary active ingredient of the licorice root, potently neutralizes SARS-CoV-2 by inhibiting the viral main protease. Our experiments highlight glycyrrhizin as a potential antiviral compound that should be further investigated for the treatment of COVID-19.
Production, Reproduction and Adaptation characteristics of Boran cattle breed under changing climate: A systematic review and meta-analysis
Authors: Bayssa Merga , Yigrem Sintayehu , Betsa Simret , Tolera Adugna
Published: December 2020

Introduction

Climate change has devastating effects on livestock production and productivity, which could threaten livestock-based food security in pastoral and agro-pastoral production systems of the tropics and sub-tropics. Hence, to sustain livestock production in an environment challenged by climate change, the animals must have the ability to survive and produce under extreme conditions. Boran cattle breed is one of the hardiest Zebu cattle reared by Borana Oromo pastoralists for milk and meat production. This paper aims to compile the main production, reproduction and adaptation traits of Boran cattle based on systematic review amd meta-analysis of peer reviewed and published articles on the subject.

Methodology

Combination of systematic review and meta-analysis based on PRISMA guideline was employed. Accordingly, out of 646 recorded articles identified through database searching, 64 were found to be eligible for production, reproduction and adaptation characteristics of the Boran cattle, twenty-eight articles were included in qualitative systematic review while 36 articles were used for quantitative meta-analysis.

Result

Boran cattle have diversity of adaptation (morphological, physiological, biochemical, metabolic, cellular and molecular) responses to the effects of climate change induced challenges - notably high temperature and solar radiation, rangeland degradation, seasonal feed and water shortages and high incidences of tropical diseases. Meta-analysis using a random-effects model showed estimates of heritability and genetic correlations for reproduction and production traits. In addition, heritability and genetic-correlation estimates found in the present study suggest that there is high genetic variability for most traits in Boran cattle, and that genetic improvement is possible for all studied traits in this breed.

Conclusion

The review revealed that Boran cattle exhibit better reproduction, production and adaption potentials as compared to other indigenous zebu cattle breeds in Ethiopia under low-land, poor pasture and water conditions. On other hand, the breed is currently challenged by adverse effects of climate change and other management factors such as high rate of genetic dilution, reduced rangeland productivity, lack of organized breed improvement programs and discriminate selection of gene pool. Thus, we recommend strategic breed improvement and genetic conservation program of Boran cattle breed in collaboration with Borana pastoralists through proper quantification of important traits and estimation of the pure Boran cattle population while controlled cross breeding strategy could be used in urban and peri-urban areas for maximum utilization of adapataion and production pottential of this breed.
Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills
Authors: Caramaschi Doretta , Neumann Alexander , Cardenas Andres , Tindula Gwen , Alemany Silvia , Zillich Lea , Pesce Giancarlo , Lahti Jari M.T. , Havdahl Alexandra , Mulder Rosa , Felix Janine F. , Tiemeier Henning , Sirignano Lea , Frank Josef , Witt Stephanie H. , Rietschel Marcella , Deuschle Michael , Huen Karen , Eskenazi Brenda , Send Tabea Sarah , Ferrer Muriel , Gilles Maria , de Agostini Maria , Baïz Nour , Rifas-Shiman Sheryl L. , Kvist Tuomas , Czamara Darina , Tuominen Samuli T. , Relton Caroline L. , Rai Dheeraj , London Stephanie J. , Räikkönen Katri , Holland Nina , Annesi-Maesano Isabella , Streit Fabian , Hivert Marie-France , Oken Emily , Sunyer Jordi , Cecil Charlotte , Sharp Gemma
Published: December 2020

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts (N=2196-3798) within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall, verbal and non-verbal cognitive scores. The associations at single CpG sites were weak for all of the cognitive domains investigated. One region nearDUSP22on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that cord blood DNA methylation at single CpGs can predict cognitive skills and further studies are needed to confirm regional differences.
Urban fox squirrels exhibit tolerance to humans but respond to stimuli from natural predators
Authors: Kittendorf Anna , Dantzer Ben
Published: December 2020

Animals in urban areas that experience frequent exposure to humans often behave differently than those in less urban areas, such as exhibiting less vigilance or anti-predator behavior. These behavioral shifts may be an adaptive response to urbanization, but it may be costly if animals in urban areas also exhibit reduced anti-predator behavior in the presence of natural predators. In trials with only a human observer as the stimulus, urban squirrels exhibited reduced vigilance and anti-predator behavior compared to those in less urban areas. Next, we exposed squirrels in multiple urban and less urban sites to acoustic playbacks of a control stimulus (non-predatory bird calls), a natural predator (hawk), and dogs and recorded their vigilance and three different anti-predator behaviors when a human approached them while either broadcasting one of these three playbacks or no playbacks at all. Squirrels at urban sites also did not differ in their behavioral responses to the playbacks from possible predators (hawks or dogs) when they were compared to those at less urban sites exposed to these playbacks. Urban squirrels also exhibited increased vigilance and anti-predator behavior when exposed to a human paired with hawk playbacks compared to the control playbacks. Together, our results indicate that urban squirrels did perceive and assess risk to the natural predator appropriately despite exhibiting increased tolerance to humans. These results provide little support for the hypothesis that increased tolerance to humans causes animals to lose their fear of natural predators.
The plot thickens: haploid and triploid-like thalli, hybridization, and biased mating type ratios inLetharia
Authors: Ament-Velásquez S. Lorena , Tuovinen Veera , Bergström Linnea , Spribille Toby , Vanderpool Dan , Nascimbene Juri , Yamamoto Yoshikazu , Thor Göran , Johannesson Hanna
Published: December 2020

The study of the reproductive biology of lichen fungal symbionts has been traditionally challenging due to their complex and symbiotic lifestyles. Against the common belief of haploidy, a recent genomic study found a triploid-like signal inLetharia. Here, we used genomic data from a pure culture and from thalli, together with a PCR survey of the MAT locus, to infer the genome organization and reproduction inLetharia. We found that the read count variation in the fourLethariaspecimens, including the pure culture derived from a single sexual spore ofL. lupina, is consistent with haploidy. By contrast, theL. lupinaread counts from a thallus’ metagenome are triploid-like. Characterization of the mating-type locus revealed a conserved heterothallic configuration across the genus, along with auxiliary genes that we identified. We found that the mating-type distributions are balanced in North America forL. vulpinaandL. lupina, suggesting widespread sexual reproduction, but highly skewed in Europe forL. vulpina, consistent with predominant asexuality. Taken together, we propose thatLethariafungi are heterothallic and typically haploid, and provide evidence that triploid-like individuals are rare hybrids betweenL. lupinaand an unknownLetharialineage, reconciling classic systematic and genetic studies with recent genomic observations.
A highly conserved binding pocket on PP2A-B56 is required for shugoshin binding and cohesion protection
Authors: Ueki Yumi , Hadders Michael , Weisser Melanie B , Nasa Isha , Gupta Tanmay , Hertz Emil T , Kruse Thomas , Montoya Guillermo , Jeyaprakash A. Arockia , Kettenbach Arminja , Lens Susanne M.A. , Nilsson Jakob
Published: December 2020

The shugoshin proteins are universal protectors of centromeric cohesin during mitosis and meiosis. The binding of human Sgo1 to the PP2A-B56 phosphatase through a coiled coil (CC) region is believed to mediate cohesion protection during mitosis. Here we undertook a structure function analysis of the PP2A-B56-Sgo1 complex, revealing unanticipated aspects of complex formation and function. We establish that a highly conserved pocket of the B56 regulatory subunit is required for Sgo1 binding and cohesion protection. Consistent with this, we show that Sgo1 blocks the binding of PP2A-B56 substrates containing a canonical B56 binding motif. Surprisingly, we identify B56 and Sgo1 mutants that prevent complex formation yet support cohesion protection and normal mitotic progression. This suggests that Sgo1 and PP2A-B56 have cohesion protection activity independently of complex formation. Collectively our work provides important insight into cohesion protection during mitosis.
Neural heterogeneity promotes robust learning
Authors: Perez-Nieves Nicolas , Leung Vincent C. H. , Dragotti Pier Luigi , Goodman Dan F. M.
Published: December 2020

The brain has a hugely diverse, heterogeneous structure. Whether or not heterogeneity at the neural level plays a functional role remains unclear, and has been relatively little explored in models which are often highly homogeneous. We compared the performance of spiking neural networks trained to carry out tasks of real-world difficulty, with varying degrees of heterogeneity, and found that it substantially improved task performance. Learning was more stable and robust, particularly for tasks with a rich temporal structure. In addition, the distribution of neuronal parameters in the trained networks closely matches those observed experimentally. We suggest that the heterogeneity observed in the brain may be more than just the byproduct of noisy processes, but rather may serve an active and important role in allowing animals to learn in changing environments.

Neural heterogeneity is metabolically efficient for learning, and optimal parameter distribution matches experimental data.
Transformed notochordal cells trigger chronic wounds destabilizing the vertebral column and bone homeostasis
Authors: Lopez-Cuevas Paco , Deane Luke , Yang Yushi , Hammond Chrissy L , Kague Erika
Published: December 2020

Notochordal cells play a pivotal role in vertebral column patterning, contributing to the formation of the inner architecture of intervertebral discs (IVDs). Their disappearance during development has been associated with reduced repair capacity and IVD degeneration. Notochordal remnants are known to cause chordomas, a highly invasive bone cancer associated with late diagnosis. Understanding the impact of neoplastic cells during development and on the surrounding vertebral column could open avenues for earlier intervention and therapeutics. We investigated the impact of transformed notochord cells in the zebrafish skeleton using a RAS expressing line in the notochord under the control of the Kita promoter, with the advantage of adulthood endurance. Transformed cells caused damage in the notochord and destabilised the sheath layer triggering a wound repair mechanism, with enrolment of sheath cells (col9a2+) and expression of wt1b, similar to induced notochord wounds. Moreover, increased recruitment of neutrophils and macrophages, displaying abnormal behaviour in proximity to the notochord sheath and transformed cells, supported parallels between chordomas, wound and inflammation. Cancerous notochordal cells interfere with differentiation of sheath cells to form chordacentra domains leading to fusions and vertebral clefts during development. Adults displayed IVD irregularities reminiscent of degeneration; reduced bone mineral density, increased osteoclast activity; while disorganised osteoblasts and collagen indicate impaired bone homeostasis. By depleting inflammatory cells, we abrogated chordoma development and rescued the skeletal features of the vertebral column. Therefore, we showed that transformed notochord cells alter the skeleton during life, causing a wound-like phenotype and activating chronic wound response, suggesting parallels between chordoma, wound, IVD degeneration and inflammation, highlighting inflammation as a promising target for future therapeutics.
Alterations in excitatory and inhibitory synaptic development within the mesolimbic dopamine pathway in a mouse model of prenatal drug exposure
Authors: Boggess Taylor , Williamson James C. , Niebergall Ethan B. , Sexton Hannah , Mazur Anna , Egleton Richard D. , Grover Lawrence M. , Risher W. Christopher
Published: December 2020

The rise in rates of opioid abuse in recent years has led to an increase in the incidence of neonatal abstinence syndrome (NAS). Despite having a greater understanding of NAS and its symptoms, there still remains a lack of information surrounding the long-term effects of prenatal exposure to drugs of abuse on neurological development. One potential outcome of prenatal drug exposure that has been increasingly explored is disruption in normal synaptogenesis within the central nervous system. Both opioids and gabapentin, an antiepileptic drug commonly co-abused by opioid abuse disorder patients, have been shown to interfere with the normal functioning of astrocytes, non-neuronal glial cells known to serve many functions, including regulation of synaptic development. The goal of this study was to investigate the effects of prenatal drug exposure on synaptogenesis within brain regions associated with the mesolimbic dopamine pathway, the primary reward pathway within the brain associated with drug abuse and addiction, in a pregnant mouse model. Immunohistochemistry (IHC) and confocal fluorescence microscopy imaging studies on the brains of postnatal day 21 (P21) mouse pups revealed a significant increase in the mean number of excitatory synapses within the anterior cingulate cortex (ACC), nucleus accumbens (NAc), and prefrontal cortex (PFC) in mice that were prenatally exposed to either the opioid drug buprenorphine or gabapentin. These studies also revealed a significant decrease in the mean number of inhibitory synapses within the NAc and PFC of mice treated with buprenorphine. This observed net increase in excitatory signaling capability within the developing mesolimbic dopamine pathway suggests that exposure to drugs of abusein uterocan trigger maladaptive neuronal connectivity that persists beyond the earliest stages of life.
Haplotype Reconstruction in Connected Tetraploid F1 Populations
Authors: Zheng Chaozhi , Amadeu Rodrigo R. , Munoz Patricio R. , Endelman Jeffrey B.
Published: December 2020

In diploid species, many multi-parental populations have been developed to increase genetic diversity and quantitative trait loci (QTL) mapping resolution. In these populations, haplotype reconstruction has been used as a standard practice to increase QTL detection power in comparison with the marker-based association analysis. To realize similar benefits in tetraploid species (and eventually higher ploidy levels), a statistical framework for haplotype reconstruction has been developed and implemented in the software PolyOrigin for connected tetraploid F1 populations with shared parents. Haplotype reconstruction proceeds in two steps: first, parental genotypes are phased based on multi-locus linkage analysis; second, genotype probabilities for the parental alleles are inferred in the progeny. PolyOrigin can utilize genetic marker data from single nucleotide polymorphism (SNP) arrays or from sequence-based genotyping; in the latter case, bi-allelic read counts can be used (and are preferred) as input data to minimize the influence of genotype call errors at low depth. To account for errors in the input map, PolyOrigin includes functionality for filtering markers, inferring inter-marker distances, and refining local marker ordering. Simulation studies were used to investigate the effect of several variables on the accuracy of haplotype reconstruction, including the mating design, the number of parents, population size, and sequencing depth. PolyOrigin was further evaluated using an autotetraploid potato dataset with a 3×3 half-diallel mating design. In conclusion, PolyOrigin opens up exciting new possibilities for haplotype analysis in tetraploid breeding populations.