bluuebunny/crossref_metadata_2025 huggingface dataset:
Source Imaging of Triphasic Waves and Other Encephalopathies
Authors: Zafar Muhammad S. , Rahman Shareena A. , Ehrenberg Joshua Andrew , Kaplan Peter W.
Published: December 2020

Purpose:

Triphasic waves (TWs) are defined as high-amplitude positive waveforms with preceding and after-going negative waves, typically seen in medically ill patients. TWs manifest in similar clinical presentations as other EEG encephalopathies; however, electrographically, they appear different. To better understand the difference, the authors used two different source localization software programs to find a reproducible and unique signature for TW.

Methods:

EEGs performed at Johns Hopkins Hospital and Duke University Hospital were retrospectively analyzed. EEG samples of TW, Delta, Theta-Delta, and Frontal Intermittent Rhythmic Delta Activity were selected. The authors did source localization via Commercial Curry 8 and open-source Brainstorm software. A minimum of 10 stereotypical waveforms per subject were selected. The authors used the Boundary Element Method for the head model, which was derived from the Montreal Neurological Institute averaged imaging data set. Dipole and current density analyses were performed.

Results:

Twenty-eight patients were selected (10 TW, 4 Frontal Intermittent Rhythmic Delta Activity, 6 Theta-Delta, and 8 Delta). The findings suggest the activation of anterior frontal and midline structures for TW. Frontal Intermittent Rhythmic Delta Activity had a similar localization but without a moving dipole. In comparison, the Delta and Delta-Theta appeared to have a more diffuse origin.

Conclusions:

Source analysis of TW via two different software suggests the anterior midline location of TW with anterior to posterior propagation. These findings correlate with the previous hypotheses of TW origin. Retrospective analysis, low number of recording electrodes, and difficult analysis of slow waves limit the interpretation of these results. Nonetheless, this article opens the prospect of future studies in this field.
Winogradskyella endarachnes sp. nov., a marine bacterium isolated from the brown alga Endarachne binghamiae
Authors: Xu Yan , Li Jin , Hu Yu , Li Haibin , Peng Tao , Zhong Mingqi , Hu Zhong
Published: December 2020

A Gram-negative, aerobic, rod-shaped, non-flagellated and motile by gliding bacterium HL2-2T, was isolated from the surface of the brown alga Endarachne binghamiae in China. The 16S rRNA gene sequence analysis showed that this strain was affiliated with the genus

Winogradskyella

in the family

Flavobacteriaceae

and presented great similarity with the type strain

Winogradskyella litoriviva

KMM 6491T (97.9 % sequence similarity). The whole genome of strain HL2-2T comprised 3.6 Mbp with a G+C content of 31.9 mol%. The average nucleotide identity between strain HL2-2T and

Winogradskyella litoriviva

KMM 6491T was 83.7 %. Growth of the isolated strain was observed from 20–40 °C (optimum, 30 °C), at pH ranged from 5.5 to 8.0 (optimum, pH 6.0) and in the presence of 0–5 % (w/v) NaCl (optimum, 0–2 %). The major fatty acids (>10 % of the total) were C16 : 0, iso-C15 : 0 and the predominant menaquinone was MK-6. The combined phylogenetic, physiological and chemotaxonomic analysis show that the strain HL2-2T represents a novel species belonging to the genus

Winogradskyella

, for which the name Winogradskyella endarachnes sp. nov. is proposed, and which the type strain is HL2-2T (=CICC 24857T=KCTC 72882T).
Kineobactrum salinum sp. nov., isolated from marine sediment
Authors: Kim Minji , Cha In-Tae , Lee Ki-Eun , Lee Byoung-Hee , Park Soo-Je
Published: December 2020

Strain M2T, isolated from marine sediment collected at Jeju Island, was an aerobic, Gram-stain-negative, oxidase- and catalase-positive, motile, rod-shaped bacterium that formed circular, raised, yellow colonies. Strain M2T grew at 15–42 °C, pH 5.5–9.0 and with 1–9 % (w/v) NaCl. Phylogenetic analysis based on its 16S rRNA gene sequences indicated that strain M2T was closely related to

Kineobactrum sediminis

F02T (98.0 % sequence similarity). Ubiquinone-8 was determined to be the sole respiratory quinone. Summed feature 3 (C16 : 1
 ω6c/C16 : 1
 ω7c) and summed feature 8 (C18 : 1
 ω7c/C18 : 1
 ω6c) were identified as the predominant fatty acids. The DNA G+C content and digital DNA–DNA relatedness between strain M2T and

K. sediminis

F02T were 60.7 mol% and 19.5 %, respectively. Phosphatidylglycerol and phosphatidylethanolamine were identified as the major polar lipids. Thus, polyphasic characterization revealed that strain M2T represents a novel species in the genus

Kineobactrum

, for which the name Kineobactrum salinum sp. nov. is proposed. The type strain is M2T (=KCTC 72815T=VTCC 910108T).
COVID-19 Trends in Florida K-12 Schools, August 10 – November 14, 2020
Authors: Jones Rebekah D.
Published: December 2020

Data collected from 38 states from August 3 – November 15, 2020 showed more than 250,000 confirmed student and staff cases of SARS-CoV-2 in K-12 schools1. Yet, analysis of COVID-19 case data in USA schools has been extremely limited2,3. To date, no large-scale or state-wide analyses by school level and grade has been published, opening a wide gap in understanding COVID-19 in American schools. A large-scale assessment of available data and trends could provide a baseline for understanding the virus in the K-12 learning environment and dispel misconceptions about the prevalence of COVID-19 in schools.

Table of Contents Summary

Using the most comprehensive database of K-12 COVID-19 case data in the country, Florida provides clues for understanding student and staff cases in schools.

What’s known on this subject

Florida schools began reopening to in-person instruction in August have reported more than 18,000 student and staff cases of COVID-19 as of November 14, 2020. Incidence of COVID-19 cases in K-12 students and staff is of urgent public health concern.

What this study adds

COVID-19 cases reported in Florida schools were most influenced by community case rates, district mask policies, and percent of students attending face-to-face. Student case rates were highest in high schools (12.5 per 1,000).
TAPER: Pinpointing errors in multiple sequence alignments despite varying rates of evolution
Authors: Zhang Chao , Zhao Yiming , Braun Edward L , Mirarab Siavash
Published: December 2020

Abstract

Erroneous data can creep into sequence datasets for reasons ranging from contamination to annotation and alignment mistakes. These errorscanreduce the accuracy of downstream analyses such as tree inference andwilldiminish the confidence of the community in the results even when they do not impact the analysis. As datasets keep getting larger, it has become difficult to visually check for errors, and thus, automatic error detection methods are needed more than ever before. Alignment masking methods, which are widely used, completely remove entire aligned sites. Therefore, theymayreduce signal as much as or more than they reduce the noise. An alternative is designing targeted methods that look for errors in small species-specific stretches of the alignment by detecting outliers. Crucially, such a method should attempt to distinguish the real heterogeneity, which includes signal, from errors. This type of error filtering is surprisingly under-explored. In this paper, we introduce TAPER, an automatic algorithm that looks for small stretches of error in sequence alignments. Our results show that TAPER removes very little data yet finds much of the error and cleans up the alignments.
Impact of COVID-19 restrictions on pre-school children’s eating, activity and sleep behaviours: a qualitative study
Authors: Clarke JL , Kipping R , Chambers S , Willis K , Taylor H , Brophy R , Hannam K , Simpson SA , Langford R
Published: December 2020

Background

In spring 2020, the COVID-19 lockdown placed unprecedented restrictions on the behaviour and movements of the UK population. Citizens were ordered to ‘stay at home’, only allowed to leave their houses to buy essential supplies, attend medical appointments or exercise once a day. This qualitative study explored how ‘lockdown’ and its subsequent easing changed young children’s everyday activities, eating and sleep habits to gain insight into the impact for health and wellbeing.

Methods

In summer 2020 we interviewed 20 parents of children due to start school in September 2020 (aged 3-5 years) by phone or video call to explore their experiences of lockdown and its easing. We recruited participants through nurseries and local Facebook community groups in the South West and West Midlands of England. Half the sample were from Black, Asian or Minority Ethnic backgrounds and half lived in the most deprived quintile. We analysed interviews using thematic analysis.

Results

Children’s activity, screen time, eating, and sleep routines had some level of disruption. Parents reported children ate more snacks during lockdown, but also spent more time preparing meals and eating as a family. Most parents reported a reduction in their children’s physical activity and an increase in screen time, which some linked to difficulties in getting their child to sleep. Parents sometimes expressed guilt about changes in activity, screen time and snacking over lockdown. Most felt these changes would be temporary with no lasting impact, though others worried about re-establishing healthy routines.

Conclusions

The spring COVID-19 lockdown negatively impacted on pre-school children’s eating, activity and sleep routines. While some positive changes were reported, there were wide-spread reports of lack of routines, habits and boundaries which, at least in the short-term, were likely to have been detrimental for child health and development. Guidance and support for families during times of COVID-19 restrictions could be valuable to help them maintain healthy activity, eating, screen-time and sleeping routines to protect child health and ensure unhealthy habits are not adopted.
Does living close to petrochemical complex increase the adverse psychological effects of COVID-19 lockdown?
Authors: Vicens Paloma , Heredia Luis , Bustamante Edgar , Pérez Yolanda , Domingo José L. , Torrente Margarita
Published: December 2020

The petrochemical industry has made possible the economic development of many local communities, increasing the employment opportunities and generating a complex network of secondary industries closely related to those. However, it is known that petrochemical industries emit air pollutants, which are related to different negative effects on mental health. In addition, many people around the world are being exposed to highly stressful situations derived from the COVID-19 pandemic and the lockdown adopted by the national and regional governments. The present study was aimed at analysing the possible differential effects on different psychological outcomes (stress, anxiety, depression and emotional regulation strategies) derived from the COVID-19 pandemic and the consequent lockdown in individuals living near an important petrochemical complex and subjects living in other areas, non-exposed to the characteristic environmental pollutants emitted by this kind of complexes. The sample was composed by 1607 subjects which respond a questionnaire developed ad hoc about the confinement conditions, the Perceived Stress Scale (PSS), the Hospital Anxiety and Depression Scale (HADS), the Barratt Impulsivity Scale (BIS) and the Emotional Regulation Questionnaire (ERQ). The results indicated that people living closer to petrochemical complexes reported greater risk perception. However, no significant relationships between psychological variables and proximity to the focus were detected when compared people living near to or far away from a chemical/petrochemical complex. Regarding the adverse psychological effects of the first lockdown due to COVID-19 on the general population in Catalonia, we can conclude that the lockdown conditions included in this survey were mainly related to changes in the impulsivity levels of participants. However, we can also suggest that the economic effects are going to be harder than those initially detected in this study. More studies are necessary to corroborate our results.

Author Contributions

Conceptualization: Paloma Vicens, Luis Heredia, José L. Domingo, Margarita Torrente

Funding Acquisition: José L. Domingo

Data Curation and Formal Analysis: Paloma Vicens, Luis Heredia, Edgar Bustamante, Yolanda Pérez, Margarita Torrente

Methodology: Paloma Vicens, Luis Heredia, Margarita Torrente

Writing-original draft: Paloma Vicens, Luis Heredia

Writing- review and editing: Paloma Vicens, Luis Heredia, Yolanda Pérez, José L. Domingo, Margarita Torrente
Is the end near? When the different countries will surmount COVID-19 pandemic: new approach applying physical, mathematical and game theory models
Authors: García de Alcañíz J. G. , López-Rodas V. , Costas E.
Published: December 2020

In the year 2020 COVID-19 pandemic was a global issue that changed mankinds lifestyle. Since then, when we will control the pandemic and recover our normal life has become the paramount question to be answered, and it needs to be solved. One problem is that there are wealthy countries, with very good health care systems and scientific resources while others barely dedicate 100 US $ per citizen per year, rich countries could cooperate at different levels with poorer ones. In such a diverse context classic epidemiology models, excellent for predicting short term evolution of the pandemic at a local level are not as suitable for long term predictions at a global scale specially if the data they use are of questionable accuracy. Alternatively, big data and AI approaches have been tried. There is an option that can be more effective. Physics applies predictive models about the duration of an event based on analysing the dynamics of the time evolution of the event itself. These models can be used alongside with probabilistic and game theory models that consider different degrees of cooperation. By means of the physics Delta-targument and a game theory model (cooperate versus defector) we calculate when different countries may control COVID-19 pandemic. In a non-cooperate model, those countries with more resources and best manage the pandemic will have it under control between May and September 2021, whereas those with no resources will suffer the pandemic until at least October 2023. On the other hand, a strong cooperative model will allow that the majority could control the COVID-19 pandemic between October 2021 and November 2022.
Transcriptional Landscape of Hepatocellular Carcinoma Reveals that Patient Ethnic-Origin Influences Patterns of Expression
Authors: Zayas Rachel , Sisson Artemio , Kuhnsman Ariana , Nagalo Bolni Marius , Roberts Lewis R. , Buetow Kenneth
Published: December 2020

The global incidence of hepatocellular carcinoma (HCC) has increased threefold in the last 30 years. In the United States, individuals with ancestry from Asia, Africa and Latin America have a significantly higher risk of developing HCC. However, the molecular mechanisms by which HCC disparities occur remain mostly understudied. Herein, we employed advanced bioinformatics analysis tools to identify genomic drivers that could explain the differences seen among HCC patients of distinct ethnicities (geographic origins). Data from TCGA and open-source software tools HiSTAT, StringTie, and Ballgown were used to map next-generation sequencing (NGS) reads from DNA and RNA, assemble transcripts, and quantify gene abundance. Differential genes/transcripts were mapped to known biomarkers and targets of systemic HCC therapeutics. Four overlapping transcripts were identified between each ethnicity group: FCN2, FCN3, COLEC10, and GDF2. However, we also found that multiple genes are expressed in an ethnicity-specific manner. Our models also revealed that both current and emerging biomarkers fail to capture heterogeneity between patients of different ethnicities. Finally, we have determined that first-line treatment, such as Sorafenib, may be better suited for Asian patients, while Lenvatinib may exhibit better efficacy for Caucasian patients. In conclusion, we have outlined that the pathways involved in early hepatocarcinogenesis may occur in an ethnicity-specific manner and that these distinct phenotypes should be taken into account for biomarker and therapeutic development.
Spatiotemporal analysis of glioma heterogeneity reveals Col1A1 as an actionable target to disrupt tumor mesenchymal differentiation, invasion and malignancy
Authors: Comba Andrea , Faisal Syed M. , Dunn Patrick J. , Argento Anna E. , Hollon Todd C. , Al-Holou Wajd N. , Varela Maria Luisa , Zamler Daniel B. , Quass Gunnar L , Apostolides Pierre F. , Abel Clifford , Brown Christine E. , Kish Phillip E. , Kahana Alon , Kleer Celina G. , Motsch Sebastien , Castro Maria G , Lowenstein Pedro R.
Published: December 2020

Intra-tumoral heterogeneity and diffuse infiltration are hallmarks of glioblastoma that challenge treatment efficacy. However, the mechanisms that set up both tumor heterogeneity and invasion remain poorly understood. Herein, we present a comprehensive spatiotemporal study that aligns distinctive intra-tumoral histopathological structures, oncostreams, with dynamic properties and a unique, actionable, spatial transcriptomic signature. Oncostreams are dynamic multicellular fascicles of spindle-like and aligned cells with mesenchymal properties, detected usingex vivoexplants andin vivointravital imaging. Their density correlates with tumor aggressiveness in genetically engineered mouse glioma models, and high-grade human gliomas. Oncostreams facilitate the intra-tumoral distribution of tumoral and non-tumoral cells, and the invasion of the normal brain. These fascicles are defined by a specific molecular signature that regulates their organization and function. Oncostreams structure and function depend on overexpression of COL1A1. COL1A1 is a central gene in the dynamic organization of glioma mesenchymal transformation, and a powerful regulator of glioma malignant behavior. Inhibition of COL1A1 eliminated oncostreams, reprogramed the malignant histopathological phenotype, reduced expression of the mesenchymal associated genes, induced changes in the tumor microenvironment and prolonged animal survival. Oncostreams represent a novel pathological marker of potential value for diagnosis, prognosis, and treatment.
Species-resolved sequencing of low-biomass microbiomes by 2bRAD-M
Authors: Sun Zheng , Huang Shi , Zhu Pengfei , Tzehau Lam , Zhao Helen , Lv Jia , Zhang Rongchao , Zhou Lisha , Niu Qianya , Wang Xiuping , Zhang Meng , Jing Gongchao , Bao Zhenmin , Liu Jiquan , Wang Shi , Xu Jian
Published: December 2020

Microbiome samples with low microbial biomass or severe DNA degradation remain challenging for amplicon-based (e.g., 16S/18S-rRNA) or whole-metagenome sequencing (WMS) approaches. Here, we introduce 2bRAD-M, a highly reduced and cost-effective metagenome-sequencing strategy which only sequences ~1% of metagenome and can simultaneously produce species-level bacterial, archaeal, and fungal profiles for low-biomass and highly degraded samples. For mock communities, 2bRAD-M can accurately generate species-level taxonomic profiles for otherwise hard-to-sequence samples with (i) low biomass of merely 1 pg of total DNA, (ii) high host DNA contamination (99%), and (iii) severely fragmented DNA (50-bp) from degraded samples. Tests of 2bRAD-M on stool, skin and environment-surface samples deliver successful reconstruction of comprehensive, high-resolution microbial profiles with agreement across 16S-rRNA, WMS and existing literature. In addition, it enables microbial profiling in formalin-fixed paraffin-embedded (FFPE) cervical tissue samples which were recalcitrant to conventional approaches due to the low amount and heavy degradation of microbial DNA, and discriminated healthy tissue, pre-invasive cancer and invasive cancer via species-level microbial profiles with 91.1% accuracy. Therefore, 2bRAD-M greatly expands the reach of microbiome sequencing.
New self-identities evolve via point mutation in an invertebrate allorecognition gene
Authors: Huene Aidan , Chen Traci , Nicotra Matthew L.
Published: December 2020

Many organisms use genetic self-recognition systems to distinguish themselves from other members of their species. To understand how new self-identities evolve, we studied Allorecognition 2 (Alr2), a self-recognition gene from the colonial cnidarian,Hydractinia symbiolongicarpus.Alr2encodes a highly polymorphic transmembrane protein that discriminates self from non-self by selectively binding across cell membranes to other Alr2 proteins with identical or very similar sequences. Here, we show that new Alr2 proteins evolve by amino acid substitutions that immediately create isoforms with entirely novel binding specificities, or through intermediates with relaxed binding specificities. Our results also suggest a topology for homophilic interactions between Alr2 proteins. These results provide direct evidence for the generation and maintenance of functional variation at an allorecognition locus and reveal that one-component and two-component self-recognition systems evolve via different mechanisms.
The Phosphorylation Status of NPH3 Affects Photosensory Adaptation During the Phototropic Response
Authors: Kimura Taro , Haga Ken , Nomura Yuko , Higaki Takumi , Nakagami Hirofumi , Sakai Tatsuya
Published: December 2020

Photosensory adaptation, which can be classified as sensor or effector adaptation, optimizes the light sensing of living organisms by tuning their sensitivity to changing light conditions. During the phototropic response in Arabidopsis (Arabidopsis thaliana), the light-dependent expression controls of blue-light photoreceptor phototropin1 (phot1) and its modulator ROOT PHOTOTROPISM2 (RPT2) are known as the molecular mechanisms underlying sensor adaptation. However, little is known about effector adaption in plant phototropism. Here we show that control of the phosphorylation status of NONPHOTOTROPIC HYPOCOTYL3 (NPH3) leads to effector adaptation in hypocotyl phototropism. We identified seven phosphorylation sites of NPH3 proteins in the etiolated seedlings of Arabidopsis and generated unphosphorable and phosphomimetic NPH3 proteins on those sites. Unphosphorable NPH3 showed a shortening of its subcellular localization in the cytosol and caused an inability to adapt to very low fluence rates of blue light (∼10−5µmol m−2s−1) during the phototropic response. In contrast, the phosphomimetic NPH3 proteins had a lengthened subcellular localization in the cytosol and could not lead to the adaptation for blue light at fluence rates of 10−3µmol m−2s−1or more. Our results suggest that the activation levels of phot1 and the corresponding phosphorylation levels of NPH3 determine the rate of plasma membrane-cytosol shuttling of NPH3, which moderately maintains the active state of phot1 signaling across a broad range of blue-light intensities and contributes to the photosensory adaptation of phot1 signaling during the phototropic response in hypocotyls.

One sentence summary

The phosphorylation status of NON-PHOTOTROPIC HYPOCOTYL3 proteins affects their subcellular localization and the photosensory adaptation of phot1 signaling.
A competition of critics in human decision-making
Authors: Enkhtaivan Enkhzaya , Nishimura Joel , Ly Cheng , Cochran Amy
Published: December 2020

Recent experiments and theories of human decision-making suggest positive and negative errors are processed and encoded differently by serotonin and dopamine, with serotonin possibly serving to oppose dopamine and protect against risky decisions. We introduce a temporal difference (TD) model of human decision-making to account for these features. Our model involves two critics, an optimistic learning system and a pessimistic learning system, whose predictions are integrated in time to control how potential decisions compete to be selected. Our model predicts that human decision-making can be decomposed along two dimensions: the degree to which the individual is sensitive to (1) risk and (2) uncertainty. In addition, we demonstrate that the model can learn about reward expectations and uncertainty, and provide information about reaction time despite not modeling these variables directly. Lastly, we simulate a recent experiment to show how updates of the two learning systems could relate to dopamine and serotonin transients, thereby providing a mathematical formalism to serotonin’s hypothesized role as an opponent to dopamine. This new model should be useful for future experiments on human decision-making.
COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types
Authors: Schmiedel Benjamin J. , Chandra Vivek , Rocha Job , Gonzalez-Colin Cristian , Bhattacharyya Sourya , Madrigal Ariel , Ottensmeier Christian H. , Ay Ferhat , Vijayanand Pandurangan
Published: December 2020

Common genetic polymorphisms associated with severity of COVID-19 illness can be utilized for discovering molecular pathways and cell types driving disease pathogenesis. Here, we assessed the effects of 679 COVID-19-risk variants on gene expression in a wide-range of immune cell types. Severe COVID-19-risk variants were significantly associated with the expression of 11 protein-coding genes, and overlapped with either target gene promoter orcis-regulatory regions that interact with target promoters in the cell types where their effects are most prominent. For example, we identified that the association between variants in the 3p21.31 risk locus and the expression ofCCR2in classical monocytes is likely mediated through an active cis-regulatory region that interacted withCCR2promoter specifically in monocytes. The expression of several other genes showed prominent genotype-dependent effects in non-classical monocytes, NK cells, B cells, or specific T cell subtypes, highlighting the potential of COVID-19 genetic risk variants to impact the function of diverse immune cell types and influence severe disease manifestations.
Strength in numbers: Large-scale integration of single-cell transcriptomic data reveals rare, transient muscle progenitor cell states in muscle regeneration
Authors: McKellar David W. , Walter Lauren D. , Song Leo T. , Mantri Madhav , Wang Michael F.Z. , De Vlaminck Iwijn , Cosgrove Benjamin D.
Published: December 2020

Skeletal muscle repair is driven by the coordinated self-renewal and fusion of myogenic stem and progenitor cells. Single-cell gene expression analyses of myogenesis have been hampered by the poor sampling of rare and transient cell states that are critical for muscle repair, and do not provide spatial information that is needed to understand the context in which myogenic differentiation occurs. Here, we demonstrate how large-scale integration of new and public single-cell and spatial transcriptomic data can overcome these limitations. We created a large-scale single-cell transcriptomic dataset of mouse skeletal muscle by integration, consensus annotation, and analysis of 23 newly collected scRNAseq datasets and 79 public single-cell (scRNAseq) and single-nucleus (snRNAseq) RNA-sequencing datasets. The resulting compendium includes nearly 350,000 cells and spans a wide range of ages, injury, and repair conditions. Combined, these data enabled identification of the predominant cell types in skeletal muscle with robust, consensus gene expression profiles, and resolved cell subtypes, including endothelial subtypes distinguished by vessel-type of origin, fibro/adipogenic progenitors marked by stem potential, and many distinct immune populations. The representation of different experimental conditions and the depth of transcriptome coverage enabled robust profiling of sparsely expressed genes. We built a densely sampled transcriptomic model of myogenesis, from stem-cell quiescence to myofiber maturation and identified rare, short-lived transitional states of progenitor commitment and fusion that are poorly represented in individual datasets. We performed spatial RNA sequencing of mouse muscle at three time points after injury and used the integrated dataset as a reference to achieve a high-resolution, local deconvolution of cell subtypes. This analysis identified the temporal variation in the colocalization of immune cell subtype interactions with myogenic progenitors during injury recovery. We provide a public web tool to enable interactive exploration and visualization of this rich single-cell transcriptomic resource. Our work supports the utility of large-scale integration of single-cell transcriptomic data as a tool for biological discovery.
Pan-genome analysis of Mycobacterium tuberculosis identifies accessory genome sequences deleted in modern Beijing lineage
Authors: Rufai Syed Beenish , Ozer Egon A. , Singh Sarman
Published: December 2020

Beijing sub-lineage of Mycobacterium tuberculosis has been reported to have increased transmissibility and drug resistance. This led us to get insights of genomic landscape of modern Beijing sub-lineages in comparison with other lineages of M. tuberculosis utilizing pan-genomics approach. Pangenome analysis was performed using software Spine (v0.2.3), AGEnt (v0.2.3) and ClustAGE (v0.7.6). The average pangenome size was 45,40,849 bp with 4,391 coding sequences (CDS), with a GC content of 65.4%. The size of the core genome was 36,83,161 bp, contained 3,698 CDS and had an average GC content of 65.1%. The average accessory genome size was 6,96,320.9 bp, with 539.4 CDS and GC content of 67.9%. Among the accessory elements complete deletion of CRISPR-associated endoribonuclease cas1 (Rv2817c), cas2 (Rv2816c), CRISPR type III-a/mtube-associated protein csm6 (Rv2818c), CRISPR type III-a/mtube-associated ramp protein csm5 (Rv2819c) and partial deletion (61.5%) CRISPR type III-a/mtube-associated ramp protein csm4 (Rv2820c) sequences was found specifically in modern Beijing lineages taken in assortment. The sequences were validated using conventional PCR method, which precisely amplified the corresponding targets of sequence elements with 100% sensitivity and specificity. Deletion of accessory CRISPR sequence elements amongst the modern Beijing sub-lineage of M. tuberculosis suggest more defective DNA-repair in these strains which may enhance virulence of the strains. Further, the developed conventional PCR approach for detection of virulent modern Beijing lineage may be of interest to public health and outbreak control organizations for rapid detection of modern Beijing lineage.
Climate change impacts on the phylogenetic diversity of the world’s terrestrial birds: more than species numbers
Authors: Voskamp Alke , Hof Christian , Biber Matthias F. , Hickler Thomas , Niamir Aidin , Willis Stephen G. , Fritz Susanne A.
Published: December 2020

Ongoing climate change is a major threat to biodiversity and impacts on species distributions and abundances are already evident. Heterogenous responses of species due to varying abiotic tolerances and dispersal abilities have the potential to further amplify or ameliorate these impacts through changes in species assemblages. Here we investigate the impacts of climate change on terrestrial bird distributions and, subsequently, on species richness as well as on different aspects of phylogenetic diversity of species assemblages across the globe. We go beyond previous work by disentangling the potential impacts on assemblage phylogenetic diversity of species gains vs. losses under climate change and compare the projected impacts to randomized assemblage changes.

We show that climate change might not only affect species numbers and composition of global species assemblages but could also have profound impacts on assemblage phylogenetic diversity, which, across extensive areas, differ significantly from random changes. Both the projected impacts on phylogenetic diversity and on phylogenetic structure vary greatly across the globe. Projected increases in the evolutionary history contained within species assemblages, associated with either increasing phylogenetic diversification or clustering, are most frequent at high northern latitudes. By contrast, projected declines in evolutionary history, associated with increasing phylogenetic over-dispersion or homogenisation, are projected across all continents.

The projected widespread changes in the phylogenetic structure of species assemblages show that changes in species richness do not fully reflect the potential threat from climate change to ecosystems. Our results indicate that the most severe changes to the phylogenetic diversity and structure of species assemblages are likely to be caused by species range shifts rather than range reductions and extinctions. Our findings highlight the importance of considering diverse measures in climate impact assessments and the value of integrating species-specific responses into assessments of entire community changes.
Alpha activity neuromodulation induced by individual alpha-based neurofeedback learning in ecological context: A double-blind randomized study
Authors: Grosselin Fanny , Breton Audrey , Yahia-Cherif Lydia , Wang Xi , Spinelli Giuseppe , Hugueville Laurent , Fossati Philippe , Attal Yohan , Navarro-Sune Xavier , Chavez Mario , George Nathalie
Published: December 2020

The neuromodulation induced by neurofeedback training (NFT) remains a matter of debate. Investigating the modulation of brain activity specifically associated with NF requires controlling for multiple factors, such as reward, performance, congruency between task and targeted brain activity. This can be achieved using sham feedback (FB) control condition, equating all aspects of the experiment but the link between brain activity and FB. We aimed at investigating the modulation of individual alpha EEG activity induced by NFT in a double-blind, randomized, sham-controlled study. Forty-eight healthy participants were assigned to either NF (n=25) or control (n=23) group and performed alpha upregulation training (over 12 weeks) with a wearable EEG device. Participants of the NF group received FB based on their individual alpha activity. The control group received the auditory FB of participants of the NF group. An increase of alpha activity across training sessions was observed in the NF group only (p<0.001). This neuromodulation was selective in that it was not observed for theta (4-8Hz) and low beta (13-18Hz) activities. While alpha upregulation was found in the NF group only, psychological outcome variables showed increased feeling of control, decreased anxiety level and increased relaxation feeling in both the NF and control groups, without any significant difference between groups. This is interpreted in terms of learning context and placebo effects. Our results pave the way to self-learnt, NF-based neuromodulation with light-weighted, wearable EEG systems.
Scalable production of tissue-like vascularised liver organoids from human PSCs
Authors: Harrison Sean P , Siller Richard , Tanaka Yoshiaki , Xiang Yangfei , Patterson Benjamin , Kempf Henning , Melum Espen , Åsrud Kathrine S , Chollet Maria E , Andersen Elisabeth , Sandset Per Morten , Baumgarten Saphira , Bonanini Flavio , Kurek Dorota , Mathapati Santosh , Almaas Runar , Sharma Kulbhushan , Wilson Steven R , Skottvoll Frøydis S , Boger Ida C , Bogen Inger L , Nyman Tuula A , Wu Jun J , Bezrouk Ales , Cizkova Dana , Mokry Jaroslav , Zweigerdt Robert , Park In-Hyun , Sullivan Gareth J
Published: December 2020

A lack of physiological parity between 2D cell culture andin vivo, has paved the way towards more organotypic models. Organoids exist for a number of tissues, including the liver. However, current approaches to generate hepatic organoids suffer drawbacks, including a reliance on extracellular matrices (ECM), the requirement to pattern in 2D culture, costly growth factors and a lack of cellular diversity, structure and organisation. Current hepatic organoid models are generally simplistic, composed of hepatocytes or cholangiocytes, which renders them less physiologically relevant when compared to native tissue. Here we aim to address these drawbacks. To address this, we have developed an approach that does not require 2D patterning, is ECM independent combined with small molecules to mimic embryonic liver development that produces massive quantities of liver like organoids. Using single-cell RNA sequencing and immunofluorescence we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, innervation and a population of resident macrophage – the Kupffer cells. The organoids exhibit key liver functions including drug metabolism, serum protein production, coagulation factor production, bilirubin uptake and urea synthesis. The organoids can be transplanted and maintained in mice producing human albumin long term. The organoids exhibit a complex cellular repertoire reflective of the organ, havede novovascularization and innervation, enhanced function and maturity. This is a pre-requisite for a myriad of applications from cellular therapy, tissue engineering, drug toxicity assessment, disease modeling, to basic developmental biology.
Cobamide sharing drives skin microbiome dynamics
Authors: Swaney Mary Hannah , Sandstrom Shelby , Kalan Lindsay R
Published: December 2020

The human skin microbiome is a key player in human health, with diverse functions ranging from defense against pathogens to education of the immune system. While recent studies have begun to shed light on the valuable role that skin microorganisms have in maintaining a healthy skin barrier, a detailed understanding of the complex interactions that shape healthy skin microbial communities is limited. Cobamides, the vitamin B12 class of cofactor, are essential for organisms across the tree of life. Because this vitamin is only produced by a limited fraction of prokaryotes, cobamide sharing has been shown to mediate community dynamics within microbial communities. Here, we provide the first large-scale unbiased metagenomic assessment of cobamide biosynthesis and utilization in the skin microbiome. We show that while numerous and diverse taxa across the major bacterial phyla on the skin are cobamide dependent, relatively few species encode for de novo cobamide biosynthesis. We find that cobamide sharing shapes the network structure in microbial communities across the different microenvironments of the skin and that changes in community structure and microbiome diversity are driven by the abundance of cobamide producers in the Corynebacterium genus, in both healthy and disease skin states. Lastly, we find that de novo cobamide biosynthesis is enriched only in host-associated Corynebacterium species, including those prevalent on human skin. We confirm that the cofactor is produced in excess through quantification of cobamide production by skin-associated species isolated in the laboratory. Taken together, our results support a role for cobamide sharing within skin microbial communities, which we predict stabilizes the microbiome and mediates host interactions.
Effect of Variations in the Conserved Residues E371 and S359 on the Structural Dynamics of Protein Z Dependent Protease Inhibitor (ZPI): A Molecular Dynamic Simulation Study
Authors: Subash Chellam Gayathri , Gupta Suchetana , Suresh Aravind , Senapati Sanjib , Sengupta Tanusree
Published: December 2020

Protein Z (PZ) dependent protease inhibitor (ZPI) is a natural anticoagulant inhibiting blood coagulation proteases fXa and fXIa. Despite being a member of the serpin superfamily, it possesses unique structural features such as activation by PZ that regulate its inhibitory function. It is well known that effecient protease inhibition by serpins is dependent on the dynamics of its reactive center loop (RCL). In order to understand the RCL dynamics of ZPI, we performed Molecular Dynamics (MD) simulation on ZPI and its E371 and S359 variants located at important conserved functional sites. Unexpectedly, the RCL of E371 variants, such as E371K, E371R, and E371Q, were shown to be very stable due to compensatory interactions at the proximal end of RCL. Interestingly, RCL flexibility was shown to be enhanced in the double mutant K318-E371 due to the repulsive effect of increased negative charge on top of the breach region. Principal component analysis (PCA) coupled with residue wise interaction network (RIN) revealed correlated motion between the RCL and the PZ binding regions in the WT. Whereas the analysis revealed a loss of regulation in correlated motion between RCL and PZ binding hotspot Tyr240 in the double mutant. Additionally, the S359F and S359I mutations also resulted in increased RCL flexibility owing to the disruption of stabilizing hydrogen bonding interaction at the N terminal end of S5A. Thus, the current study proposes that the overall stabilizing interactions of S5A is a major regulator of proper loop movement of ZPI for protease inhibition and therefore its activity. The results would be beneficial to engineer activity compromised ZPI mutants as a prophylactic agent for the treatment of hemophilia.
Mistakes can stabilise the dynamics of rock-paper-scissors games
Authors: Kleshnina Maria , Streipert Sabrina S. , Filar Jerzy A. , Chatterjee Krishnendu
Published: December 2020

A game of rock-paper-scissors is an interesting example of an interaction where none of the pure strategies strictly dominates all others, leading to a cyclic pattern. In this work, we consider an unstable version of rock-paper-scissors dynamics and allow individuals to make behavioural mistakes during the strategy execution. We show that such an assumption can break a cyclic relationship leading to a stable equilibrium emerging with only one strategy surviving. We consider two cases: completely random mistakes when individuals have no bias towards any strategy and a general form of mistakes. Then, we determine conditions for a strategy to dominate all other strategies. However, given that individuals who adopt a dominating strategy are still prone to behavioural mistakes in the observed behaviour, we may still observe extinct strategies. That is, behavioural mistakes in strategy execution stabilise evolutionary dynamics leading to an evolutionary stable and, potentially, mixed co-existence equilibrium.

Author summary

A game of rock-paper-scissors is more than just a children’s game. This type of interactions is often used to describe competition among animals or humans. A special feature of such an interaction is that none of the pure strategies dominates, resulting in a cyclic pattern. However, in wild communities such interactions are rarely observed by biologists. Our results suggest that this lack of cyclicity may stem from imperfectness of interacting individuals. In other words, we show analytically that heterogeneity in behavioural patterns may break a cyclic relationship and lead to a stable equilibrium in pure or mixed strategies.
Optimal CD8+T-cell memory formation following subcutaneous cytomegalovirus infection requires virus replication but not early dendritic cell responses
Authors: Dimonte Sandra , Gimeno-Brias Silvia , Marsden Morgan , Chapman Lucy , Sabberwal Pragati , Clement Mathew , Humphreys Ian R
Published: December 2020

Cytomegalovirus (CMV) induction of large frequencies of highly functional memory T-cells has attracted much interest in the utility of CMV-based vaccine vectors, with exciting preclinical data obtained in models of infectious diseases and cancer. However, pathogenesis of human CMV (HCMV) remains a concern. Attenuated CMV-based vectors, such as replication- or spread-deficient viruses potentially offer an alternative to fully replicating vectors. However, it is not well-understood how CMV attenuation impacts vector immunogenicity, in particularly when administered via relevant routes of immunization such as the skin. Herein we used the murine cytomegalovirus (MCMV) model to investigate the impact of vector attenuation on T-cell memory formation following subcutaneous administration. We found that the spread deficient virus (ΔgL-MCMV) was impaired in its ability to induce memory CD8+T-cells reactive to some (M38, IE1) but not all (IE3) viral antigens. Impaired memory T-cell development was associated with a preferential and pronounced loss of polyfunctional (IFN-γ+TNF-α+) T-cells, and was not rescued by increasing the dose of replication-defective MCMV. Finally, whilst vector attenuation reduced dendritic cell (DC) recruitment to skindraining lymph nodes, systematic depletion of multiple DC subsets during acute subcutaneous MCMV infection had a negligible impact on T-cell memory formation, implying that attenuated responses induced by replication-deficient vectors were likely not a consequence of impaired initial DC activation. Thus, overall, these data imply that the choice of antigen and/or cloning strategy of exogenous antigen in combination with the route of immunization may influence the ability of attenuated CMV vectors to induce robust functional T-cell memory.
Novel Mutations in NSP1 and PLPro of SARS-CoV-2 NIB-1 Genome Mount for Effective Therapeutics
Authors: Hossain Mohammad Uzzal , Bhattacharjee Arittra , Emon Md. Tabassum Hossain , Chowdhury Zeshan Mahmud , Mosaib Md. Golam , Moniruzzaman Md. , Rahman Md. Hadisur , Islam Md. Nazrul , Ahmed Irfan , Amin Md. Ruhul , Rashed Asif , Das Keshob Chandra , Keya Chaman Ara , Salimullah Md.
Published: December 2020

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiologic agent of Coronavirus Disease-2019 (COVID-19), is rapidly accumulating new mutations. Analysis of these mutations is necessary for gaining knowledge regarding different aspects of therapeutic development. Recently, we have reported a Sanger method based genome sequence of a viral isolate named SARS-CoV-2 NIB-1, circulating in Bangladesh. The genome has four novel mutations in V121D, V843F, A889V and G1691C positions. V121D substitution has the potential to destabilize the Non-Structural Protein (NSP-1) which inactivates the type-1 Interferon-induced antiviral system hence this mutant could be the basis of attenuated vaccines against SARS-CoV-V843F, A889V and G1691C are all located in NSP3. G1691C can decrease the flexibility of the protein while V843F and A889V changed the binding pattern of SARS-CoV-2 Papain-Like protease (PLPro) inhibitor GRL0617. V843F PLPro showed reduced affinity for Interferon Stimulating Gene-15 (ISG-15) protein whereas V843F+A889V double mutants exhibited the same binding affinity as wild type PLPro. Here, V843F is a conserved position of PLPro that damaged the structure but A889V, a less conserved residue, most probably neutralized that damage. Mutants of NSP1 could provide attenuated vaccines against coronavirus. Also, these mutations of PLPro could be targeted to develop anti-SARS therapeutics.