bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural ordering of thePlasmodium bergheicircumsporozoite protein repeats by inhibitory antibody 3D11
Authors: Kucharska Iga , Thai Elaine , Srivastava Ananya , Rubinstein John , Pomès Régis , Julien Jean-Philippe
Published: June 2020

Plasmodiumsporozoites express circumsporozoite protein (CSP) on their surface, an essential protein that contains central repeating motifs. Antibodies targeting this region can neutralize infection, and the partial efficacy of RTS,S/AS01 – the leading malaria vaccine againstP. falciparum(Pf) – has been associated with the humoral response against the repeats. Although structural details of antibody recognition of PfCSP have recently emerged, the molecular basis of antibody-mediated inhibition of otherPlasmodiumspecies via CSP binding remains unclear. Here, we analyze the structure and molecular interactions of potent monoclonal antibody (mAb) 3D11 binding toP. bergheiCSP (PbCSP) using molecular dynamics simulations, X-ray crystallography, and cryoEM. We reveal that mAb 3D11 can accommodate all subtle variances of the PbCSP repeating motifs, and, upon binding, induces structural ordering of PbCSP through homotypic interactions. Together, our findings uncover common mechanisms of antibody evolution in mammals against the CSP repeats ofPlasmodiumsporozoites.
The derlin Dfm1 promotes retrotranslocation of folded protein domains from the endoplasmic reticulum
Authors: Fonseca Daniel , Carvalho Pedro
Published: June 2020

Endoplasmic reticulum (ER) proteins are degraded by proteasomes in the cytosol through ER-associated degradation (ERAD). This process involves retrotranslocation of substrates across the ER membrane, their ubiquitination and subsequent membrane extraction by the Cdc48/Npl4/Ufd1 ATPase complex prior delivery to proteasomes for degradation. Recently a mechanism for the retrotranslocation of misfolded substrates by the Hrd1 ubiquitin ligase complex was described. However, how substrates with folded luminal domains are retrotranslocated remains unknown. Here, we identify Dfm1 as an essential membrane component for the retrotranslocation of proteins with folded luminal domains. Both Dfm1 intramembrane rhomboid-like and the cytosolic Cdc48-binding domains are essential for substrate retrotranslocation. Substrate processing by Dfm1 and Cdc48 complex requires the ubiquitin shuttle factors Rad23/Dsk2 and the multi-ubiquitination enzyme Ufd2. Our findings suggest a pathway in which a series of ubiquitin modifying factors recruit Dfm1 to resolve a stalled retrotranslocation intermediate due to the presence of a folded luminal domain.
A TRANSPARENT, OPEN-SOURCE SIRD MODEL FOR COVID19 DEATH PROJECTIONS IN INDIA
Authors: Agarwal Ananye , Tyagi Utkarsh
Published: June 2020

Abstract

As India emerges from the lockdown with ever higher COVID19 case counts and a mounting death toll, reliable projections of case numbers and deaths counts are critical in informing policy decisions. We examine various existing models and their shortcomings. Given the amount of uncertainty surrounding the disease we choose a simple SIRD model with minimal assumptions enabling us to make robust predictions. We employ publicly available mobility data from Google to estimate social distancing covariates which influence how fast the disease spreads. We further present a novel method for estimating the uncertainty in our predictions based on first principles. To demonstrate, we fit our model to three regions (Spain, Italy, NYC) where the peak has passed and obtain predictions for the Indian states of Delhi and Maharashtra where the peak is desperately awaited.
Viral load dynamics in transmissible symptomatic patients with COVID-19
Authors: Kawasuji Hitoshi , Takegoshi Yusuke , Kaneda Makito , Ueno Akitoshi , Miyajima Yuki , Kawago Koyomi , Fukui Yasutaka , Yoshida Yoshihiko , Kimura Miyuki , Yamada Hiroshi , Sakamaki Ippei , Tani Hideki , Morinaga Yoshitomo , Yamamoto Yoshihiro
Published: June 2020

To investigate the relationship between viral load and secondary transmission in novel coronavirus disease 2019 (COVID-19), we reviewed epidemiological and clinical data obtained from immunocompetent laboratory-confirmed patients with COVID-19 at Toyama University Hospital. In total, 28 patients were included in the analysis. Median viral load at the initial sample collection was significantly higher in adults than in children and in symptomatic than in asymptomatic patients. Among symptomatic patients, non-linear regression models showed that the estimated viral load at onset was higher in the index (patients who transmitted the disease to at least one other patient) than in the non-index patients (patients who were not the cause of secondary transmission; median [95% confidence interval]: 6.6 [5.2–8.2] vs. 3.1 [1.5–4.8] log copies/μL, respectively). High nasopharyngeal viral loads around onset may contribute to secondary transmission of COVID-19.

Article Summary Line

High nasopharyngeal viral load around the onset may contributes to secondary transmission of COVID-19.
Increased serum levels of sCD14 and sCD163 indicate a preponderant role for monocytes in COVID-19 immunopathology
Authors: Gómez-Rial J , Currás-Tuala MJ , Rivero-Calle I , Gómez-Carballa A , Cebey-López M , Rodríguez-Tenreiro C , Dacosta-Urbieta A , Rivero-Velasco C , Rodríguez-Núñez N , Trastoy-Pena R , Rodríguez-García J , Salas A , Martinón-Torres F
Published: June 2020

Background

Emerging evidence indicates a potential role for monocyte in COVID-19 immunopathology. We investigated two soluble markers of monocyte activation, sCD14 and sCD163, in covid19 patients with the aim of characterizing their potential role in monocyte-macrophage disease immunopathology. To the best of our knowledge, this is the first study of its kind.

Methods

Fifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group.

Results

sCD14 and sCD163 levels were significantly higher among COVID-19 patients, independently of ICU admission requirement, compared to the control group. We found a significant correlation between sCD14 levels and other inflammatory markers, particularly Interleukin-6, in the non-ICU patients’ group. sCD163 showed a moderate positive correlation with the time at sampling from admission, increasing its value over time, independently of severity group.

Conclusions

Monocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. These data suggest a potentially preponderant role for monocyte-macrophage activation in the development of immunopathology of covid19 patients.
An MRI-based, data-driven model of cortical laminar connectivity
Authors: Shamir Ittai , Assaf Yaniv
Published: June 2020

Over the past two centuries, great scientific efforts have been spent on deciphering the structure and function of the cerebral cortex using a wide variety of methods. Since the advent of MRI neuroimaging, significant progress has been made in imaging of global white matter connectivity (connectomics), followed by promising new studies regarding imaging of grey matter laminar compartments. Despite progress in both fields, there still lacks mesoscale information regarding cortical laminar connectivity that could potentially bridge the gap between the current resolution of connectomics and the relatively higher resolution of cortical laminar imaging. Here, we systematically review a sample of prominent published articles regarding cortical laminar connectivity, in order to offer a simplified data-driven model that integrates white and grey matter MRI datasets into a novel way of exploring whole-brain tissue-level connectivity. Although it has been widely accepted that the cortex is exceptionally organized and interconnected, studies on the subject display a variety of approaches towards its structural building blocks. Our model addresses three principal cortical building blocks: cortical layer definitions (laminar grouping), vertical connections (intraregional, within the cortical microcircuit and subcortex) and horizontal connections (interregional, including connections within and between the hemispheres). While cortical partitioning into layers is more widely accepted as common knowledge, certain aspects of others such as cortical columns or microcircuits are still being debated. This study offers a broad and simplified view of histological and microscopical knowledge in laminar research that is applicable to the limitations of MRI methodologies, primarily regarding specificity and resolution.
Climatic influence on the magnitude of COVID-19 outbreak: a stochastic model-based global analysis
Authors: Pramanik Malay , Chowdhury Koushik , Juel Rana Md , Bisht Praffulit , Pal Raghunath , Szabo Sylvia , Pal Indrajit , Behera Bhagirath , Liang Qiuhua , Padmadas Sabu S. , Udmale Parmeshwar
Published: June 2020

This study examines the association between community transmission of COVID-19 cases and climatic predictors, considering travel information and annual parasite index across the three climatic zones, i.e., tropical, subtropical, and temperate. A Boosted Regression Tree model has been employed to understand the association between the COVID-19 cases. The results show that average temperature and average relative humidity are the major contributors in explaining the differentials of COVID-19 transmission in temperate and subtropical regions whereas the mean diurnal temperature range and temperature seasonality are the most significant determinants in tropical regions. The average temperature is the most influential factor affecting the number of COVID-19 cases in France, Turkey, the US, the UK, and Germany, and the cases decrease sharply above 10°C. Among the tropical countries, India found to be most affected by mean diurnal temperature, and Brazil fazed by temperature seasonality. Most of the temperate countries like France, USA, Turkey, UK, and Germany with an average temperature between 5–12°C had high number of COVID-19 cases. The findings are expected to add to the ongoing debates on the influence of climatic factors influencing the number of COVID-19 cases and could help researchers and policymakers to make appropriate decisions for preventing the spread.

Highlights

Analyzed influence of climatic & bioclimatic factors on the spread of COVID-19

First to analyze COVID-19 cases in 228 cities globally across three climatic zones

Temperature & humidity influenced COVID-19 cases in temperate & sub-tropics

Mean diurnal temperature & temperature seasonality had effects in tropics

Low temperature elicits COVID-19 cases in France, Turkey, the US, the UK, & Germany

Graphical abstract
SARS-CoV-2 receptor is co-expressed with elements of the kinin-kallikrein, renin-angiotensin and coagulation systems in alveolar cells
Authors: Sidarta-Oliveira Davi , Jara Carlos Poblete , Ferruzzi Adriano J. , Skaf Munir S. , Velander William H. , Araujo Eliana P. , Velloso Licio A.
Published: June 2020

SARS-CoV-2, the pathogenic agent of COVID-19, employs angiotensin converting enzyme-2 (ACE2) as its cell entry receptor. Clinical data reveal that in severe COVID-19, SARS-CoV-2 infects the lung, leading to a frequently lethal triad of respiratory insufficiency, acute cardiovascular failure, and coagulopathy. Physiologically, ACE2 plays a role in the regulation of three systems that could potentially be involved in the pathogenesis of severe COVID-19: the kinin-kallikrein system, resulting in acute lung inflammatory edema; the renin-angiotensin system, promoting cardiovascular instability; and the coagulation system, leading to thromboembolism. Here we analyzed ~130,000 human lung single-cell transcriptomes and show that key elements of the kinin-kallikrein, renin-angiotensin and coagulation systems are co-expressed with ACE2 in alveolar cells, which could explain how changes in ACE2 promoted by SARS- CoV-2 cell entry result in the development of the three most severe clinical components of COVID-19.
Long-term SARS-CoV-2 RNA Shedding and its Temporal Association to IgG Seropositivity
Authors: Agarwal Vineet , Venkatakrishnan AJ , Puranik Arjun , Kirkup Christian , Lopez-Marquez Agustin , Challener Douglas W. , O’Horo John C. , Binnicker Matthew J. , Kremers Walter K. , Faubion William A. , Badley Andrew D. , Williams Amy W. , Gores Gregory J. , Halamka John D. , Morice William G. , Soundararajan Venky
Published: June 2020

Analysis of 851 COVID-19 patients with a SARS-CoV-2-positive PCR at follow-up shows 99 patients remained SARS-CoV-2-positive after four weeks from initial diagnosis. Surprisingly, a majority of these long-term viral RNA shedders were not hospitalized (61 of 99), with variable PCR Crossing point values over the month post diagnosis. For the 851-patient cohort, the mean lower bound of viral RNA shedding was 17.3 days (SD: 7.8), and the mean upper bound of viral RNA shedding from 668 patients transitioning to confirmed PCR-negative status was 22.7 days (SD: 11.8). Among 104 patients with an IgG test result, 90 patients were seropositive to date, with mean upper bound of time to seropositivity from initial diagnosis being 37.8 days (95%CI: 34.3-41.3). Juxtaposing IgG/PCR tests revealed that 14 of 90 patients are non-hospitalized and seropositive yet shed viral RNA. This study emphasizes the need for monitoring viral loads and neutralizing antibody titers in long-term shedders.
Infectivity of symptomatic malaria patients to Anopheles farauti colony mosquitoes in Papua New Guinea
Authors: Timinao Lincoln , Vinit Rebecca , Katusele Michelle , Koleala Tamarah , Nate Elma , Czeher Cyrille , Schofield Louis , Felger Ingrid , Mueller Ivo , Laman Moses , Robinson Leanne J. , Karl Stephan
Published: June 2020

Despite being a weak point in their life cycle, transmission of Plasmodium parasites from humans to mosquitoes is an understudied field of research. Direct membrane feeding assays (DMFA) are an important tool, allowing detailed mechanistic malaria transmission studies from humans to mosquitoes. Especially for Plasmodium vivax, which cannot be cultured long-term under laboratory conditions, implementation of DMFAs requires proximity to P. vivax endemic areas. In the present study, we investigated the infectivity of symptomatic Plasmodium infections to Anopheles farauti colony mosquitoes in Papua New Guinea (PNG), a country with one of the highest rates of Plasmodium vivax in the world. A total of 182 DMFAs were performed with venous blood collected from symptomatic malaria patients positive by rapid diagnostic test (RDT). DMFAs resulted in mosquito infection in 20.9% (38/182) of cases. The parasite species in the blood feeds were determined retrospectively by expert light microscopy and quantitative real-time qPCR. Based on light microscopy, 9.2% of P. falciparum and 42% of P. vivax human infections resulted in mosquito infections. Infections containing gametocytes detected by microscopy led to mosquito infections in 58.8% of P. vivax and 8.7% of P. falciparum infections. Based on qPCR, 10% of P. falciparum and 43.6% of P. vivax lead to a successful mosquito infection. Venous blood samples from symptomatic P. vivax patients were more infectious to An. farauti mosquitoes in DMFAs compared to P. falciparum infected patients. The capacity to perform DMFAs in a high-burden P. vivax setting creates a unique opportunity to address critical gaps in our understanding of P. vivax human-tomosquito transmission.
Decreased plasma levels of the survival factor renalase are associated with worse outcomes in COVID-19
Authors: Wang Melinda , Guo Xiaojia , Chun Hyung J , Lee Alfred Ian , Cha Charles , Gorelick Fred , Desir Gary V
Published: June 2020

Introduction

Renalase (RNLS), a novel secreted plasma flavoprotein, has anti-inflammatory effects in a variety of disease processes. Severe COVID-19 disease is associated with disordered inflammatory responses. We hypothesized that reduced plasma RNLS levels could be a marker of COVID-19 disease severity.

Methods

Plasma was collected from 51 hospitalized COVID-19 patients and 15 uninfected non-hospitalized controls. Plasma RNLS and cytokine levels were measured and sociodemographic and clinical data were collected from chart review. Data were analyzed using nonparametric analyses and Kaplan Meir curve log rank analysis.

Results

Plasma RNLs levels were negatively correlated with inflammatory markers, including IL-1β, IL-6, and TNFα (p = 0.04, p = 0.03, p = 0.01, respectively). Patients with COVID-19 disease had lower levels of RNLS than controls. Lower levels of RNLS were associated with more severe disease among COVID-19 patients. Low RNLS was also associated with worse survival among COVID-19 patients (HR = 4.54; 95% CI: 1.06-19.43; p = 0.005).

Conclusion

Low plasma RNLS levels are associated with severe COVID-19 disease and may be a useful additional biomarker when identifying patients with severe COVID-19 disease. Given RNLS’ antiinflammatory properties and negative correlation with inflammatory markers, these findings also suggest evidence of a potential pathophysiological mechanism for severe COVID-19 disease.
In situ measurement of intracellular thermal conductivity using heater-thermometer hybrid diamond nanosensor
Authors: Sotoma Shingo , Zhong Chongxia , Kah James Chen Yong , Yamashita Hayato , Plakhotnik Taras , Harada Yoshie , Suzuki Madoka
Published: June 2020

Understanding heat dissipation processes at nanoscale during cellular thermogenesis is essential to clarify the relationships between the heat and biological processes in cells and organisms. A key parameter determining the heat flux inside a cell is the local thermal conductivity, a factor poorly investigated both experimentally and theoretically. Here, using a nanoheater/nanothermometer hybrid based on a polydopamine shell encapsulating a fluorescent diamond nanocrystal, we measured the intracellular thermal conductivity of HeLa cell with a spatial resolution of about 200 nm. Its mean value of 0.11 Wm-1K-1 determined for the first time is significantly smaller than that of water. Bayesian analysis of the data strongly supports the existence of variation of the intracellular thermal conductivity of about 40%. These results present a major milestone towards understanding the intracellular heat transfer phenomena at nanoscale.
Asymmetric phospholipids impart novel biophysical properties to lipid bilayers allowing environmental adaptation
Authors: Smith Paul , Owen Dylan M. , Lorenz Christian D. , Makarova Maria
Published: June 2020

Phospholipids are a diverse group of biomolecules consisting of a hydrophilic head group and two hydrophobic acyl tails. The nature of the head and length and saturation of the acyl tails are important for defining the biophysical properties of lipid bilayers. It has recently been shown that the membranes of certain yeast species contain high levels of unusual asymmetric phospholipids, consisting of one long and one medium chain acyl moiety – a configuration not common in mammalian cells or other well studied model yeast species. This raises the possibility that structurally asymmetric phospholipids impart novel biophysical properties to the yeast membranes. Here, we use atomistic molecular dynamics simulations (MD) and environmentally-sensitive fluorescent membrane probes to characterize key biophysical parameters of membranes formed from asymmetric lipids for the first time. Interestingly, we show that saturated, but asymmetric phospholipids maintain membrane lipid order across a wider range of temperatures and do not require acyl tail unsaturation or sterols to maintain their properties. This may allow cells to maintain membrane fluidity even in environments which lack the oxygen required for the synthesis of unsaturated lipids and sterols.
SPOTlight: Seeded NMF regression to Deconvolute Spatial Transcriptomics Spots with Single-Cell Transcriptomes
Authors: Elosua Marc , Nieto Paula , Mereu Elisabetta , Gut Ivo , Heyn Holger
Published: June 2020

The integration of orthogonal data modalities greatly supports the interpretation of transcriptomic landscapes in complex tissues. In particular, spatially resolved gene expression profiles are key to understand tissue organization and function. However, spatial transcriptomics (ST) profiling techniques lack single-cell resolution and require a combination with single-cell RNA sequencing (scRNA-seq) information to deconvolute the spatially indexed datasets. Leveraging the strengths of both data types, we developed SPOTlight, a computational tool that enables the integration of ST with scRNA-seq data to infer the location of cell types and states within a complex tissue. SPOTlight is centered around a seeded non-negative matrix factorization (NMF) regression, initialized using cell-type marker genes, and non-negative least squares (NNLS) to subsequently deconvolute ST capture locations (spots). Using synthetic spots, simulating varying reference quantities and qualities, we confirmed high prediction accuracy also with shallowly sequenced or small-sized scRNA-seq reference datasets. We trained the NMF regression model with sample-matched or external datasets, resulting in accurate and sensitive spatial predictions. SPOTlight deconvolution of the mouse brain correctly mapped subtle neuronal cell states of the cortical layers and the defined architecture of the hippocampus. In human pancreatic cancer, we successfully segmented patient sections into healthy and cancerous areas, and further fine-mapped normal and neoplastic cell states. Trained on an external pancreatic tumor immune reference, we charted the localization of clinical-relevant and tumor-specific immune cell states. Using SPOTlight to detect regional enrichment of immune cells and their co-localization with tumor and adjacent stroma provides an illustrative example in its flexible application spectrum and future potential in digital pathology.
Leaf reflectance can surrogate foliar economics better than physiological traits across macrophyte species
Authors: Villa Paolo , Bolpagni Rossano , Pinardi Monica , Tóth Viktor R.
Published: June 2020

Macrophytes are key players in aquatic ecosystems diversity, but knowledge on variability of their functional traits, among and within species, is still limited. Remote sensing is a high-throughput, feasible option for characterizing plant traits at different scales, provided that reliable spectroscopy models are calibrated with congruous empirical data.

We sampled leaves from six floating and emergent macrophyte species common in temperate areas, covering different phenological stages, seasons, and environmental conditions, and measured leaf reflectance (400-2500 nm) and leaf traits (dealing with photophysiology, pigments and structure). We explored optimal spectral bands combinations and established non-parametric reflectance-based models for selected traits, eventually showing how airborne hyperspectral data can capture spatial-temporal macrophyte variability.

Our key finding is that structural - leaf dry matter content, leaf mass per area - and biochemical - chlorophyll-a content and chlorophylls to carotenoids ratio - traits can be surrogated by leaf reflectance with relative error under 20% across macrophyte species, while performance of reflectance-based models for photophysiological traits depends on species.

This finding shows the link between leaf reflectance and leaf economics (structure and biochemistry) for aquatic plants, thus supporting the use of remote sensing for enhancing the level of detail of macrophyte functional diversity analysis, to intra-site and intra-species scales.
Designer protein assemblies with tunable phase diagrams in living cells
Authors: Heidenreich Meta , Georgeson Joseph M. , Locatelli Emanuele , Rovigatti Lorenzo , Nandi Saroj Kumar , Steinberg Avital , Nadav Yotam , Shimoni Eyal , Safran Samuel A. , Doye Jonathan P. K. , Levy Emmanuel D.
Published: June 2020

The self-organization of proteins into specific assemblies is a hallmark of biological systems. Principles governing protein-protein interactions have long been known. However, principles by which such nanoscale interactions generate diverse phenotypes of mesoscale assemblies, including phase-separated compartments, remains challenging to characterize and understand. To illuminate such principles, we create a system of two proteins designed to interact and form mesh-like assemblies in living cells. We devise a novel strategy to map high-resolution phase diagramsin vivo, which provide mesoscale self-assembly signatures of our system. The structural modularity of the two protein components allows straightforward modification of their molecular properties, enabling us to characterize how point mutations that change their interaction affinity impact the phase diagram and material state of the assembliesin vivo. Both, the phase diagrams and their dependence on interaction affinity were captured by theory and simulations, including out-of-equilibrium effects seen in growing cells. Applying our system to interrogate biological mechanisms of self-assembly, we find that co-translational protein binding suffices to recruit an mRNA to the designed micron-scale structures.
MINTIE: identifying novel structural and splice variants in transcriptomes using RNA-seq data
Authors: Cmero Marek , Schmidt Breon , Majewski Ian J. , Ekert Paul G. , Oshlack Alicia , Davidson Nadia M.
Published: June 2020

Genomic rearrangements can modify gene function by altering transcript sequences, and have been shown to be drivers in both cancer and rare diseases. Although there are now many methods to detect structural variants from Whole Genome Sequencing (WGS), RNA sequencing (RNA-seq) remains under-utilised as a technology for the detection of gene altering structural variants. Calling fusion genes from RNA-seq data is well established, but other transcriptional variants such as fusions with novel sequence, tandem duplications, large insertions and deletions, and novel splicing are difficult to detect using existing approaches.

To identify all types of variants in transcriptomes, we developed MINTIE, an integrated pipeline for RNA-seq data. We take a reference free approach, which combines de novo assembly of transcripts with differential expression analysis, to identify up-regulated novel variants in a case sample.

We validated MINTIE on simulated and real data sets and compared it with eight other approaches for finding novel transcriptional variants. We found MINTIE was able to detect >85% of variants while no other method was able to achieve this.

We applied MINTIE to RNA-seq data from a cohort of acute lymphoblastic leukemia (ALL) patient samples and identified several clinically relevant variants, including a recurrent unpartnered fusion involving the tumour suppressor gene RB1, and variants in ALL-associated genes: tandem duplications in IKZF1 and PAX5, and novel splicing in ETV6. We further demonstrate the utility of MINTIE to identify rare disease variants using RNA-seq, including the discovery of an inter-chromosomal translocation in the DMD gene in a patient with muscular dystrophy. We posit that MINTIE will be able to identify new disease variants across a range of cancers and other disease types.
Genomic evidence of an early evolutionary divergence event in wildSaccharomyces cerevisiae
Authors: Bendixsen Devin P , Gettle Noah , Gilchrist Ciaran , Zhang Zebin , Stelkens Rike
Published: June 2020

Comparative genome analyses have suggested East Asia to be the cradle of the domesticated microbe Brewer’s yeast (Saccharomyces cerevisiae), used in the food and biotechnology industry worldwide. Here, we provide seven new, high quality long read genomes of non-domesticated yeast strains isolated from primeval forests and other natural environments in China and Taiwan. In a comprehensive analysis of our new genome assemblies, along with other long readSaccharomycetesgenomes available, we show that the newly sequenced East Asian strains are among the closest living relatives of the ancestors of the global diversity of Brewer’s yeast, confirming predictions made from short read genomic data. Three of these strains (termed the East Asian Clade IX Complex here) share a recent ancestry and evolutionary history suggesting an early divergence from otherS. cerevisiaestrains before the larger radiation of the species, and prior to its domestication. Our genomic analyses reveal that the wild East Asian strains contain elevated levels of structural variations. The new genomic resources provided here contribute to our understanding of the natural diversity ofS. cerevisiae, expand the intraspecific genetic variation found in this this heavily domesticated microbe, and provide a foundation for understanding its origin and global colonization history.

Significance statement

Brewer’s yeast (Saccharomyces cerevisiae) is a domesticated microbe and research model organism with a global distribution, and suspected origin in East Asia. So far only limited genomic resources are available from non-domesticated lineages. This study provides seven new, high quality long read genomes of strains isolated from primeval forests and other natural environments in China and Taiwan. Comparative genomics reveal elevated levels of structural variation in this group, and early phylogenetic branching prior to the global radiation of the species. These new genomic resources expand our understanding of the evolutionary history of Brewer’s yeast, and illustrate what the ancestors of this highly successful microbe may have looked like.
Behavioral, Biochemical and Histopathological effects of Standardised Pomegranate extract with Vinpocetine, Propolis or Cocoa in a rat model of Parkinson’s disease
Authors: Ali Azza A. , Kamal Mona M. , Khalil Mona G. , Ali Shimaa A. , Elariny Hemat A. , Bekhit Amany , Wahid Ahmed
Published: June 2020

Introduction

Parkinsonism is a neurodegenerative disorder. Pomegranate (POM) has been previously shown to have a dopaminergic neuroprotective effect against Parkinsonism.

Objective

The aim of the current study is to compare the efficacy of POM, vinpocetine, Propolis, Cocoa or L-dopa using RT-induced Parkinsonism rat model.

Methods

Rats were divided into seven groups; one normal and five RT model groups. One of the RT (2.5 mg/kg sc) groups served as non-treated parkinsonism model whereas the others were treated with either L-dopa (10 mg/kg PO) or with POM (150 mg/kg PO) together with each of the following; vinpocetine (VIN) (20 mg/kg PO), Propolis (300 mg/kg PO), Cocoa (24 mg/kg PO). Motor and cognitive performances were examined using three tests (catalepsy, open-field, Y-maze). Striatal dopamine, norepinephrine, serotonin, acetylcholinesterase, GABA, Glutamate, GSK 3B, BDNF levels were assessed as well as MDA, SOD, TAC, IL-1β, TNF-α, iNOs and caspase-3. Also, histopathological examinations of different brain regions were determined.

Results

Treatment with L-dopa alone or with all POM combination groups alleviated the deficits in locomotor activities, cognition, monoamine levels, acetylcholinesterase activity, oxidative stress, and inflammatory markers as well as caspase-3 expression induced by RT.

Conclusion

Combinations of POM with each of VIN, Propolis or Cocoa have a promising disease-modifying antiparkinsonian therapy even without being given as an adjuvant to L-dopa.
PeskAAS: A near-real-time, open-source monitoring and analytics system for small-scale fisheries
Authors: Tilley Alexander , Lopes Joctan Dos Reis , Wilkinson Shaun P.
Published: June 2020

Small-scale fisheries are responsible for landing half of world’s fish catch, yet there are very sparse data on these fishing activities and associated fisheries production in time and space. Fisheries-dependent data underpin scientific guidance of management and conservation of fisheries systems, but it is inherently difficult to generate robust and comprehensive data for small-scale fisheries, particularly given their dispersed and diverse nature. In tackling this challenge, we use open source software components including the Shiny R package to build PeskAAS; an adaptable and scalable digital application that enables the collation, classification, analysis and visualisation of small-scale fisheries catch and effort data. We piloted and refined this system in Timor-Leste; a small island developing nation. The features that make PeskAAS fit-for-purpose are that it is: (i) fully open-source and free to use (ii) component-based, flexible and able to integrate vessel tracking data with catch records; (iii) able to perform spatial and temporal filtering of fishing productivity by fishing method and habitat; (iv) integrated with species-specific length-weight parameters from FishBase; (v) controlled through a click-button dashboard, that was co-designed with fisheries scientists and government managers, that enables easy to read data summaries and interpretation of context-specific fisheries data. With limited training and code adaptation, the PeskAAS workflow has been used as a framework on which to build and adapt systematic, standardised data collection for small-scale fisheries in other contexts. Automated analytics of these data can provide fishers, managers and researchers with insights into a fisher’s experience of fishing efforts, fisheries status, catch rates, economic efficiency and geographic preferences and limits that can potentially guide management and livelihood investments.
In Silicodesign and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins
Authors: Kathwate Gunderao H
Published: June 2020

COVID 19 is disease caused by novel corona virus, SARS-CoV2 originated in China most probably of Bat origin. Till date, no specific vaccine or drug has been discovered to tackle the infections caused by SARS-CoV2. In response to this pandemic, we utilized bioinformatics knowledge to develop efficient vaccine candidate against SARS-CoV2. Designed vaccine was rich in effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Predicted BCR and TCR epitopes were antigenic in nature non-toxic and probably non-allergen. Modelled and refined tertiary structure was predicted as valid for further use. Protein-Protein interaction prediction of TLR2/4 and designed vaccine indicates promising binding. Designed multiepitope vaccine has induced cell mediated and humoral immunity along with increased interferon gamma response. Macrophages and dendritic cells were also found increased over the vaccine exposure.In silicocodon optimization and cloning in expression vector indicates that vaccine can be efficiently expressed inE. coli. In conclusion, predicted vaccine is a good antigen, probable no allergen and has potential to induce cellular and humoral immunity.
Examining and fine-tuning the selection of glycan compositions with GlyConnect Compozitor
Authors: Robin Thibault , Mariethoz Julien , Lisacek Frédérique
Published: June 2020

A key point in achieving accurate intact glycopeptide identification is the definition of the glycan composition file that is used to match experimental with theoretical masses by a glycoproteomics search engine. At present, these files are mainly built from searching the literature and/or querying data sources focused on posttranslational modifications. Most glycoproteomics search engines include a default composition file that is readily used when processing mass spectrometry data. We introduce here a glycan composition visualising and comparative tool associated with the GlyConnect database and called GlyConnect Compozitor. It has web interface through which the database can be queried to bring out contextual information relative to a set of glycan compositions. The tool takes advantage of compositions being related to one another through shared monosaccharide counts and outputs interactive graphs summarising information searched in the database. These results provide a guide for selecting or deselecting compositions in a file in order to reflect the context of a study as closely as possible. As part of the tool collection of the Glycomics@ExPASy initiative, Compozitor is hosted athttps://glyconnect.expasy.org/compozitor/where it can be run as a web application. It is also directly accessible from the GlyConnect database.
Denisovan ancestry and population history of early East Asians
Authors: Massilani Diyendo , Skov Laurits , Hajdinjak Mateja , Gunchinsuren Byambaa , Tseveendorj Damdinsuren , Yi Seonbok , Lee Jungeun , Nagel Sarah , Nickel Birgit , Devièse Thibaut , Higham Tom , Meyer Matthias , Kelso Janet , Peter Benjamin M. , Pääbo Svante
Published: June 2020

We present analyses of the genome of a ~34,000-year-old hominin skull cap discovered in the Salkhit Valley in North East Mongolia. We show that this individual was a female member of a modern human population that, following the split between East and West Eurasians, experienced substantial gene flow from West Eurasians. Both she and a 40,000-year-old individual from Tianyuan outside Beijing carried genomic segments of Denisovan ancestry. These segments derive from the same Denisovan admixture event(s) that contributed to present-day mainland Asians but are distinct from the Denisovan DNA segments in present-day Papuans and Aboriginal Australians.
Oocyte spindle assembly depends on multiple interactions between HP1 and the CPC
Authors: Wang Lin-Ing , DeFosse Tyler , Jang Janet K. , Battaglia Rachel A. , Wagner Victoria F. , McKim Kim S.
Published: June 2020

The chromosomes in the oocytes of many animals appear to promote bipolar spindle assembly. InDrosophilaoocytes, spindle assembly requires the chromosome passenger complex (CPC), which consists of INCENP, Borealin, Survivin and Aurora B. To determine what recruits the CPC to the chromosomes and its role in spindle assembly, we developed a strategy to manipulate the function and localization of INCENP, which is critical for recruiting the Aurora B kinase. We found that an interaction between Borealin and the chromatin is crucial for the recruitment of the CPC to the chromosomes and is sufficient to build kinetochores and recruit spindle microtubules. We also found that HP1 moves from the chromosomes to the spindle microtubules along with the CPC. We propose that the interaction with HP1 promotes the movement of the CPC from the chromosomes to the microtubules. In addition, within the central spindle, rather than at the centromeres, the CPC and HP1 are required for homologous chromosome bi-orientation.
Early phylodynamics analysis of the COVID-19 epidemic in France
Authors: Danesh Gonché , Elie Baptiste , Michalakis Yannis , Sofonea Mircea T , Bal Antonin , Behillil Sylvie , Destras Grégory , Boutolleau David , Burrel Sonia , Marcelin Anne-Geneviève , Plantier Jean-Christophe , Thibault Vincent , Simon-Loriere Etienne , van der Werf Sylvie , Lina Bruno , Josset Laurence , Enouf Vincent , Alizon Samuel ,   the COVID SMIT PSL group
Published: June 2020

France was one of the first countries to be reached by the COVID-19 pandemic. Here, we analyse 196 SARS-Cov-2 genomes collected between Jan 24 and Mar 24 2020, and perform a phylodynamics analysis. In particular, we analyse the doubling time, reproduction number (ℛt) and infection duration associated with the epidemic wave that was detected in incidence data starting from Feb 27. Different models suggest a slowing down of the epidemic in Mar, which would be consistent with the implementation of the national lock-down on Mar 17. The inferred distributions for the effective infection duration andℛtare in line with those estimated from contact tracing data. Finally, based on the available sequence data, we estimate that the French epidemic wave originated between mid-Jan and early Feb. Overall, this analysis shows the potential to use sequence genomic data to inform public health decisions in an epidemic crisis context and calls for further analyses with denser sampling.
Perfluoroalkyl Substances are increased in patients with Late-Onset Ulcerative colitis and induce Intestinal Barrier defects ex vivo in Murine Intestinal tissue
Authors: Fart Frida , Salihović Samira , McGlinchey Aidan , Gareau Melanie G. , Orešič Matej , Halfvarson Jonas , Hyötyläinen Tuulia , Schoultz Ida
Published: June 2020

Background

Environmental factors are strongly implicated in late-onset of inflammatory bowel disease. Here, we investigate whether high exposure to perfluoroalkyl substances correlates with (1) late-onset inflammatory bowel disease, and (2) disturbances of the bile acid pool. We further explore the effect of the specific perfluoroalkyl substance perfluoronoctanoic acid on intestinal barrier function in murine tissue.

Methods

Serum levels of perfluoroalkyl substances and bile acids were assessed by ultra-performance liquid chromatography coupled to a triple-quadrupole mass spectrometer in matched samples from patients with ulcerative colitis (n=20) and Crohn’s disease (n=20) diagnosed at the age of ≥55 years. Age and sex-matched blood donors (n=20), were used as healthy controls. Ex vivo Ussing chamber experiments were performed to assess the effect of perfluoronoctanoic acid on ileal and colonic murine tissue (n=9).

Results

The total amount of perfluoroalkyl substances was significantly increased in patients with ulcerative colitis compared to healthy controls and patients with Crohn’s disease (p<0.05). Ex vivo exposure to perfluoronoctanoic acid induced a significanlty altered ileal and colonic barrier function. The distribution of bile acids, as well as the correlation pattern between (1) perfluoroalkyl substances and (2) bile acids, differed between patient and control groups.

Conclusion

Our results demonstrate that perfluoroalkyl substances levels are increased in patients with late-onset ulcerative colitis and may contribute to the disease by inducing a dysfunctional intestinal barrier.
Microvascular blood flow changes of the abductor pollicis brevi muscle during sustained static exercise
Authors: Giovannella Martina , Urtane Evelina , Karadeniz Umut , Rubins Uldis , Weigel Udo M. , Marcinkevics Zbignevs , Durduran Turgut
Published: June 2020

A practical assessment of the health of the palm muscle, abductor pollicis brevis (APB), is important for diagnosis of different conditions. Here we have developed a protocol and a probe to utilize diffuse correlation spectroscopy (DCS) to characterize microvascular blood flow changes in the APB during and after sustained isometric exercise, during and after thumb abduction at at 55% of maximum voluntary contraction (MVC). Blood flow in the APB decreased during exercise in the subjects (n=13) with high MVC (n=7) and stayed constant in the ones with low MVC (n=6) suggesting that the mechanical occlusion due to increased intramuscular pressure exceeded the vasodilation elicited by the higher demand. Blood flow changes during exercise negatively correlated with the absolute force applied by each subject. Muscular blood flow increased after exercise compared to the values reached during exercise. In conclusion, DCS allows the study of the response of a small muscle to static exercise.
Genetic polymorphisms mediating behavioural and immune response to pathogens may moderate the impact of the COVID-19 pandemic: a pilot study
Authors: Rajkumar Ravi Philip
Published: June 2020

Background

The COVID-19 pandemic has affected the entire world, but there are wide variations in prevalence and mortality across nations. Genetic variants which influence behavioural or immune responses to pathogens, selected for by pathogen pressure, may influence this variability. Two relevant polymorphisms in this context are the s allele of the serotonin transporter promoter (5-HTTLPR) and the G allele of the interleukin-6 gene (IL-6 rs1800795).

Methods

The frequencies of the 5-HTTLPR s allele and IL-6 rs1800795 G allele were obtained from published data. The correlations between these allele frequencies and the prevalence and mortality rates of COVID-19 were examined across 44 nations.

Results

The IL-6 rs1800795 G allele was negatively correlated with COVID-19 prevalence (ρ = −0.466, p < 0.01) and mortality (ρ = −0.591, p<0.001) across nations. The 5-HTTLPR s allele was negatively correlated with COVID-19 mortality rates (ρ = −0.437, p = 0.023).

Conclusions

These results suggest that a significant relationship exists between genetic variants that influence behavioural and immune responses to pathogens and indices of the impact of COVID-19 across nations. Further investigation of these variants and their correlates may permit the development of better preventive or therapeutic strategies in the management of the COVID-19 pandemic.
Cytokeratin-18 has potential as a biomarker of drug-induced liver injury in European and African patients on treatment for tuberculosis
Authors: Rupprechter Sarah AE , Sloan Derek J , Oosthuyzen Wilna , Bachmann Till T , Hill Adam T , Dhaliwal Kevin , Templeton Kate , Matovu Joshua , Sekaggya-Wiltshire Christine , Dear James W
Published: June 2020

Patients on anti-tuberculosis (anti-TB) therapy are at risk of developing drug-induced liver injury (DILI). Cytokeratin-18 (K18) is an exploratory DILI biomarker that has been developed predominately in Caucasian populations and not African populations in whom TB is common. Our aim was to determine the K18 concentration in different populations with mycobacterial infection and investigate whether K18 has potential as a biomarker of anti-TB DILI.

European patients receiving anti-TB therapy were recruited at the Royal Infirmary of Edinburgh, UK (ALISTER - ClinicalTrials.gov Identifier: NCT03211208). African patients with HIV-TB coinfection, receiving anti-TB and anti-retroviral therapy (ART), were recruited at the Infectious Diseases Institute, Kampala, Uganda (SAEFRIF - NCT03982277). Serial blood samples, demographic and clinical data were collected. K18 was quantified using the M65 ELISA.

The study had 235 participants (healthy volunteers (n=28); ALISTER: active TB (n=30), latent TB (n=88), non-tuberculous mycobacterial infection (n=25); SAEFRIF: HIV-TB coinfection (n=64)). There was no difference in K18 across the groups and treatment did not affect K18 in the absence of DILI. Alanine transaminase activity (ALT) and K18 were correlated (r=0.42, 95%CI=0.34-0.49, P<0.0001). Variability was higher for K18 than ALT. There were two DILI cases: baseline ALT was 18 and 28 IU/1, peak ALT 431 and 194 IU/L; baseline K18 58 and 219 U/L, peak K18 1247 and 3490 U/L, respectively.

Circulating K18 was comparable in UK and Ugandan patients. K18 correlated with ALT and increased with DILI. Further work should determine the diagnostic and prognostic utility of K18 in this global context-of-use.
Competition between maturation and degradation drives human snRNA 3′ end quality control
Authors: Lardelli Rea M. , Lykke-Andersen Jens
Published: June 2020

Polymerases and exonucleases act on 3′ ends of nascent RNAs to promote their maturation or degradation but how the balance between these activities is controlled to dictate the fates of cellular RNAs remains poorly understood. Here, we identify a central role for the human DEDD deadenylase TOE1 in distinguishing the fates of small nuclear (sn)RNAs of the spliceosome from unstable genome-encoded snRNA variants. We found that TOE1 promotes maturation of all regular RNA polymerase II transcribed snRNAs of the major and minor spliceosomes by removing posttranscriptional oligo(A) tails, trimming 3′ ends, and preventing nuclear exosome targeting. In contrast, TOE1 promotes little to no maturation of tested U1 variant snRNAs, which are instead targeted by the nuclear exosome. These observations suggest that TOE1 is positioned at the center of a 3′ end quality control pathway that selectively promotes maturation and stability of regular snRNAs while leaving snRNA variants unprocessed and exposed to degradation in what could be a widespread mechanism of RNA quality control given the large number of noncoding RNAs processed by DEDD deadenylases.