bluuebunny/crossref_metadata_2025 huggingface dataset:
Violations of the Clausius–Duhem inequality in Couette flows of granular media
Authors: Ostoja-Starzewski Martin , Laudani Rossella
Published: December 2020

Spontaneous violations of the Clausius–Duhem (CD) inequality in Couette-type collisional flows of model granular media are studied. Planar systems of monosized circular discs (with disc numbers from 10 to 204, and disc diameters from 0.001 m to 1 m) with frictional-Hookean contacts are simulated under periodic boundary conditions by a molecular dynamics. The scale-dependent homogenization of micropolar media is used to determine the energy balances and mechanical entropy production. The dissipation function exhibits spontaneous negative entropy increments described by the fluctuation theorem. The boundary between violations and non-violations of the CD inequality is mapped in the parameter space, where the probability of such events diminishes with the disc diameter, the disc number and the area fraction increasing. The dissipation function is a random process, tending to Gaussian as the number of discs increases, and possessing non-trivial fractal and anti-persistent Hurst properties.
Familiarity breeds success: pairs that meet earlier experience increased breeding performance in a wild bird population
Authors: Culina Antica , Firth Josh A. , Hinde Camilla A.
Published: December 2020

In socially monogamous animals, including humans, pairs can meet and spend time together before they begin reproduction. However, the pre-breeding period has been challenging to study in natural populations, and thus remains largely unexplored. As such, our understanding of the benefits of mate familiarity is almost entirely limited to assessments of repeated breeding with a particular partner. Here, we used fine-scale tracking technology to gather 6 years of data on pre-breeding social associations of individually marked great tits in a wild population. We show that pairs which met earlier in the winter laid their eggs earlier in all years. Clutch size, number of hatched and fledged young, and hatching and fledging success were not influenced by parents' meeting time directly, but indirectly: earlier laying pairs had larger clutches (that also produce higher number of young), and higher hatching and fledging success. We did not detect a direct influence of the length of the initial pairing period on future mating decisions (stay with a partner or divorce). These findings suggest a selective advantage for a new pair to start associating earlier (or for individuals to mate with those they have known for longer). We call for more studies to explore the generality of fitness effects of pair familiarity prior to first breeding, and to elucidate the mechanisms underlying these effects.
Do sex hormones at birth predict later-life economic preferences? Evidence from a pregnancy birth cohort study
Authors: van Leeuwen Boris , Smeets Paul , Bovet Jeanne , Nave Gideon , Stieglitz Jonathan , Whitehouse Andrew
Published: December 2020

Economic preferences may be shaped by exposure to sex hormones around birth. Prior studies of economic preferences and numerous other phenotypic characteristics use digit ratios (2D : 4D), a purported proxy for prenatal testosterone exposure, whose validity has recently been questioned. We use
direct
measures of neonatal sex hormones (testosterone and oestrogen), measured from umbilical cord blood (
n
= 200) to investigate their association with later-life economic preferences (risk preferences, competitiveness, time preferences and social preferences) in an Australian cohort (Raine Study Gen2). We find no significant associations between testosterone at birth and preferences, except for competitiveness, where the effect runs opposite to the expected direction. Point estimates are between 0.05–0.09 percentage points (pp) and 0.003–0.14 s.d. We similarly find no significant associations between 2D : 4D and preferences (
n
= 533, point estimates 0.003–0.02 pp and 0.001–0.06 s.d.). Our sample size allows detecting effects larger than 0.11 pp or 0.22 s.d. for testosterone at birth, and 0.07 pp or 0.14 s.d. for 2D : 4D (
α
= 0.05 and power = 0.90). Equivalence tests show that most effects are unlikely to be larger than these bounds. Our results suggest a reinterpretation of prior findings relating 2D : 4D to economic preferences, and highlight the importance of future large-sample studies that permit detection of small effects.
How do developmental and parental exposures to predation affect personality and immediate behavioural plasticity in the snail
Physa acuta
?
Authors: Tariel Juliette , Plénet Sandrine , Luquet Emilien
Published: December 2020

Individuals differ in personality and immediate behavioural plasticity. While developmental environment may explain this group diversity, the effect of parental environment is still unexplored—a surprising observation since parental environment influences mean behaviour. We tested whether developmental and parental environments impacted personality and immediate plasticity. We raised two generations of
Physa acuta
snails in the laboratory with or without developmental exposure to predator cues. Escape behaviour was repeatedly assessed on adult snails with or without predator cues in the immediate environment. On average, snails were slower to escape if they or their parents had been exposed to predator cues during development. Snails were also less plastic in response to immediate predation risk on average if they or their parents had been exposed to predator cues. Group diversity in personality was greater in predator-exposed snails than unexposed snails, while parental environment did not influence it. Group diversity in immediate plasticity was not significant. Our results suggest that only developmental environment plays a key role in the emergence of group diversity in personality, but that parental environment influences mean behavioural responses to the environmental change. Consequently, although different, both developmental and parental cues may have evolutionary implications on behavioural responses.
When parasites persist: tapeworms survive host extinction and reveal waves of dispersal across Beringia
Authors: Galbreath Kurt E. , Toman Heather M. , Li Chenhong , Hoberg Eric P.
Published: December 2020

Investigations of intercontinental dispersal between Asia and North America reveal complex patterns of geographic expansion, retraction and isolation, yet historical reconstructions are largely limited by the depth of the record that is retained in patterns of extant diversity. Parasites offer a tool for recovering deep historical insights about the biosphere, improving the resolution of past community-level interactions. We explored biogeographic hypotheses regarding the history of dispersal across Beringia, the region intermittently linking Asia and North America, through large-scale multi-locus phylogenetic analyses of the genus
Schizorchis
, an assemblage of host-specific cestodes in pikas (Lagomorpha: Ochotonidae). Our genetic data support palaeontological evidence for two separate geographic expansions into North America by
Ochotona
in the late Tertiary, a history that genomic evidence from extant pikas does not record. Pikas descending from the first colonization of Miocene age persisted into the Pliocene, subsequently coming into contact with a second wave of Nearctic colonists from Eurasia before going extinct. Spatial and temporal overlap of historically independent pika populations provided a window for host colonization, allowing persistence of an early parasite lineage in the contemporary fauna following the extinction of its ancestral hosts. Empirical evidence for ancient ‘ghost assemblages' of hosts and parasites demonstrates how complex mosaic faunas are assembled in the biosphere through episodes of faunal mixing encompassing parasite lineages across deep and shallow time.
Landscape features predict the current and forecast the future geographic spread of Lyme disease
Authors: Gardner Allison M. , Pawlikowski Natalie C. , Hamer Sarah A. , Hickling Graham J. , Miller James R. , Schotthoefer Anna M. , Tsao Jean I. , Allan Brian F.
Published: December 2020

Lyme disease, the most prevalent vector-borne disease in North America, is increasing in incidence and geographic distribution as the tick vector,Ixodes scapularis, spreads to new regions. We re-construct the spatial-temporal invasion of the tick and human disease in the Midwestern US, a major focus of Lyme disease transmission, from 1967 to 2018, to analyse the influence of spatial factors on the geographic spread. A regression model indicates that three spatial factors—proximity to a previously invaded county, forest cover and adjacency to a river—collectively predict tick occurrence. Validation of the predictive capability of this model correctly predicts counties invaded or uninvaded with 90.6% and 98.5% accuracy, respectively. Reported incidence increases in counties after the first report of the tick; based on this modelled relationship, we identify 31 counties where we suspectI. scapularisalready occurs yet remains undetected. Finally, we apply the model to forecast tick establishment by 2021 and predict 42 additional counties whereI. scapulariswill probably be detected based upon historical drivers of geographic spread. Our findings leverage resources dedicated to tick and human disease reporting and provide the opportunity to take proactive steps (e.g. educational efforts) to prevent and limit transmission in areas of future geographic spread.
Application of ecological and evolutionary theory to microbiome community dynamics across systems
Authors: McDonald James E. , Marchesi Julian R. , Koskella Britt
Published: December 2020

A fundamental aim of microbiome research is to understand the factors that
influence the assembly and stability of host-associated microbiomes, and their
impact on host phenotype, ecology and evolution. However, ecological and
evolutionary theories applied to predict microbiome community dynamics are
largely based on macroorganisms and lack microbiome-centric hypotheses that
account for unique features of the microbiome. This special feature sets out to
drive advancements in the application of eco-evolutionary theory to microbiome
community dynamics through the development of microbiome-specific theoretical
and conceptual frameworks across plant, human and non-human animal systems. The
feature comprises 11 research and review articles that address: (i) the effects
of the microbiome on host phenotype, ecology and evolution; (ii) the application
and development of ecological and evolutionary theories to investigate
microbiome assembly, diversity and stability across broad taxonomic scales; and
(iii) general principles that underlie microbiome diversity and dynamics. This
cross-disciplinary synthesis of theoretical, conceptual, methodological and
analytical approaches to characterizing host–microbiome ecology and
evolution across systems addresses key research gaps in the field of microbiome
research and highlights future research priorities.
Efficacy and safety of TiNO-coated stents versus drug-eluting coronary stents. Systematic literature review and meta-analysis
Authors: Daoud Frederic C. , Létinier Louis , Moore Nicholas , Coste Pierre , Karjalainen Pasi P.
Published: December 2020

Objectives

To compare clinical outcomes after percutaneous coronary intervention (PCI) using titanium-nitride-oxide coated stents (TiNOS) versus drug-eluting stents (DES) in coronary artery disease (CAD) including acute coronary syndrome (ACS).

Design

Prospective systematic literature (SLR) conducted according to PRISMA. Medline, Embase, Cochrane, Web of Science were searched in March 2018 and updated.

Setting

Interventional cardiology.

Participants

Patients with CAD, including ACS, requiring PCI.

Interventions

All prospective randomized controlled trials (RCTs) that compared clinical outcomes after PCI with DES versus TiNOS.

Outcome measures

The pooled risk ratios (RR), TiNOS over DES, with 95% confidence intervals (CI) are computed for device-oriented Major Adverse Cardiac Events (MACE), non-fatal myocardial infarction (MI), cardiac death (CD), clinically driven target lesion revascularization (TLR), probable or definite stent thrombosis (ST), total mortality, at one to five years after PCI. Pooled RRs are stratified according to baseline ACS versus other CAD. Sensitivity analysis (SA) and certainty of the evidence are rated per GRADE.

Results

Five RCTs are eligible with 1,855 patients with TiNOS versus 1,363 with DES at 1-year follow-up and 783 versus 771 at 5-year. Three RCTs included patients with ACS only. One-year RRs in ACS are: MACE 0.93 [0.72, 1.20], MI 0.48 [0.31, 0.73], CD 0.66 [0.33, 1.31], TLR 1.55 [1.10, 2.19] and ST 0.35 [0.20, 0.64]. One-year MACE, MI, and ST are robust to SA. The certainty of the evidence is high in MACE, moderate in MI, and low or very low in the other endpoints. There are too few observations to conclude about other CAD and 5-year outcomes. However, 5-year interim results are consistent with 1-year conclusions.

Conclusions

A similar risk of MACE is found in TiNOS and DES, with potentially fewer MI and ST but more TLR in TiNOS. TiNOS are safe and effective in ACS at 1-year follow-up.

Registration

PROSPERO CRD42018090622

Strengths and limitations of this study

-

Strengths:

The level of certainty of the evidence is high for the primary endpoint at one-year follow-up in patients treated for acute coronary syndrome.

The primary endpoint and critical secondary endpoints are robust to sensitivity analysis.

-

Limitations:

Outcomes in patients treated for chronic coronary artery disease cannot be analyzed.

The level of certainty of the evidence of secondary endpoints is moderate or low.

Analysis of five-year outcomes is still at an interim stage.
When might Host Heterogeneity Drive the Evolution of Asymptomatic, Pandemic Coronaviruses?
Authors: Okamoto Kenichi W. , Ong Virakbott , Wallace Robert G. , Wallace Rodrick , Chaves Luis Fernando
Published: December 2020

For most emerging infectious diseases, including SARS-Coronavirus-2 (SARS-CoV-2), pharmaceutical intervensions such as drugs and vaccines are not available, and disease surveillance followed by isolating, contact-tracing and quarantining infectious individuals is critical for controlling outbreaks. These interventions often begin by identifying symptomatic individuals. However, by actively removing pathogen strains likely to be symptomatic, such interventions may inadvertently select for strains less likely to result in symptomatic infections. Additionally, the pathogen's fitness landscape is structured around a heterogeneous host pool. In particular, uneven surveillance efforts and distinct transmission risks across host classes can drastically alter selection pressures. Here we explore this interplay between evolution caused by disease control efforts, on the one hand, and host heterogeneity in the efficacy of public health interventions on the other, on the potential for a less symptomatic, but widespread, pathogen to evolve. We use an evolutionary epidemiology model parameterized for SARS-CoV-2, as the widespread potential for silent transmission by asymptomatic hosts has been hypothesized to account, in part, for its rapid global spread. We show that relying on symptoms-driven reporting for disease control ultimately shifts the pathogen's fitness landscape and can cause pandemics. We find such outcomes result when isolation and quarantine efforts are intense, but insufficient for suppression. We further show that when host removal depends on the prevalence of symptomatic infections, intense isolation efforts can select for the emergence and extensive spread of more asymptomatic strains. The severity of selection pressure on pathogens caused by these interventions likely lies somewhere between the extremes of no intervention and thoroughly successful eradication. Identifying the levels of public health responses that facilitate selection for asymptomatic pathogen strains is therefore critical for calibrating disease suppression and surveillance efforts and for sustainably managing emerging infectious diseases.
Nothing but hot air? – On the molecular ballistic analysis of backspatter generated by and the hazard potential of blank guns
Authors: Euteneuer Jan , Gosch Annica , Courts Cornelius
Published: December 2020

Blank cartridge guns are prevalent especially in countries with laws restricting access to conventional firearms and it is a common misconception that these weapons are harmless and only used as toys or for intimidation. However, although their harming potential is well documented by numerous reports of accidents, suicides, and homicides, a systematic molecular biological investigation of traces generated by shots from blank cartridges at biological targets has not been done so far.

Herein, we investigate the occurrence and analyzability of backspatter generated by shots of different types of blank cartridge guns firing different types of blank ammunition at ballistic gelatin model cubes doped with human blood and radiological contrast agent soaked into a spongious matrix and covered with three different variants of skin simulants.

All skin simulants were penetrated and backspatter was created in 100% of the shots in amounts sufficient for forensic STR typing that resulted in correct identification of the respective blood donor. Visible backspatter was documented on the muzzle and/or inside the barrel in all cases, and in 75% of cases also on the outer surfaces and on the shooter’s hand(s).Wound cavities were measured and ranged between 1 and 4.5 cm in depth.

Discussing our findings, we provide recommendations for finding, recovering and analyzing trace material from blank guns; and presenting a comprehensive overview of the pertinent literature on injuries inflicted by blank guns we emphasize the considerable hazard potential of these devices.
Preventing a cluster from becoming a new wave in settings with zero community COVID-19 cases
Authors: Abeysuriya Romesh G , Delport Dominic , Stuart Robyn M , Sacks-Davis Rachel , Kerr Cliff C , Mistry Dina , Klein Daniel J , Hellard Margaret , Scott Nick
Published: December 2020

In settings with zero community transmission, any new SARS-CoV-2 outbreaks are likely to be the result of random incursions. The level of restrictions in place at the time of the incursion is likely to considerably affect possible outbreak trajectories. We used an agent-based model to investigate the relationship between ongoing restrictions and behavioural factors, and the probability of an incursion causing an outbreak and the resulting growth rate. We applied our model to the state of Victoria, Australia, which has reached zero community transmission as of November 2020.

We found that a future incursion has a 45% probability of causing an outbreak (defined as a 7-day average of >5 new cases per day within 60 days) if no restrictions were in place, decreasing to 23% with a mandatory masks policy, density restrictions on venues such as restaurants, and if employees worked from home where possible. A drop in community symptomatic testing rates was associated with up to a 10-percentage point increase in outbreak probability, highlighting the importance of maintaining high testing rates as part of a suppression strategy.

Because the chance of an incursion occurring is closely related to border controls, outbreak risk management strategies require an integrated approaching spanning border controls, ongoing restrictions, and plans for response. Each individual restriction or control strategy reduces the risk of an outbreak. They can be traded off against each other, but if too many are removed there is a danger of accumulating an unsafe level of risk. The outbreak probabilities estimated in this study are of particular relevance in assessing the downstream risks associated with increased international travel.
Forecasting trachoma control and identifying transmission-hotspots
Authors: Blumberg Seth , Prada Joaquin M , Tedijanto Christine , Deiner Michael S , Godwin William W. , Emerson Paul M. , Hooper Pamela J , Borlase Anna , Hollingsworth T. Deirdre , Oldenburg Catherine E. , Porco Travis C , Arnold Benjamin F. , Lietman Thomas M ,   Trachoma survey collaborators
Published: December 2020

Background

Tremendous progress towards elimination of trachoma as a public health problem has been made. However, there are areas where the clinical indicator of disease, trachomatous inflammation—follicular (TF), remains prevalent. We quantify the progress that has been made, and forecast how TF prevalence will evolve with current interventions. We also determine the probability that a district is a transmission-hotspot based on its TF prevalence (i.e. reproduction number greater than one).

Methods

Data on trachoma prevalence comes from the GET2020 global repository organized by the World Health Organization and the International Trachoma Initiative. Forecasts of TF prevalence and the percent of districts achieving local control is achieved by regressing the coefficients of a fitted exponential distribution for the year-by-year distribution of TF prevalence. The probability of a district being a transmission-hotspot is extrapolated from the residuals of the regression.

Results

Forecasts suggest that with current interventions, 96.5% of surveyed districts will have TF prevalence among children aged 1-9 years <5% by 2030 (95% CI: 86.6-100.0%). Districts with TF prevalence < 20% appear unlikely to be transmission-hotspots. However, a district having TF prevalence of over 28% in 2016-2019 corresponds to at least 50% probability of being a transmission-hotspot.

Conclusions

Sustainable control of trachoma appears achievable. However there are transmission-hotspots that are not responding to annual mass drug administration of azithromycin and require enhanced treatment in order to reach local control
Identification of molecular candidates which regulate calcium-dependent CD8+T-cell cytotoxicity
Authors: Zöphel Sylvia , Schwär Gertrud , Nazarieh Maryam , Konetzki Verena , Hoxha Cora , Meese Eckart , Hoth Markus , Helms Volkhard , Hamed Mohamed , Schwarz Eva C.
Published: December 2020

Cytotoxic CD8+T lymphocytes (CTL) eliminate infected cells or transformed tumour cells by releasing perforin-containing cytotoxic granules at the immunological synapse. The secretion of such granules depends on Ca2+-influx through store operated Ca2+channels, formed by STIM-activated Orai proteins. Whereas molecular mechanisms of the secretion machinery are well understood, much less is known about the molecular machinery that regulates the efficiency of Ca2+-dependent target cell killing. Here, we isolated total RNA from natural killer (NK) cells, non-stimulated CD8+T-cells, and from Staphylococcus aureus enterotoxin A (SEA) stimulated CD8+T-cells (SEA-CTL) and conducted whole genome expression profiling by microarray experiments. Based on differential expression analysis of the transcriptome data and analysis of master regulator genes, we identified 31 candidates which potentially regulate Ca2+-homeostasis in CTL. To investigate a putative function of these candidates in CTL cytotoxicity, we transfected either SEA-stimulated CTL (SEA-CTL) or antigen specific CD8+T-cell clones (CTL-MART-1) with siRNAs specific against the identified candidates and analyzed the killing capacity using a real-time killing assay. In addition, we complemented the analysis by studying the effect of inhibitory substances acting on the candidate proteins if available. Finally, to unmask their involvement in Ca2+dependent cytotoxicity, candidates were also analyzed under Ca2+-limiting conditions. Overall, this strategy led to the identification of KCNN4, RCAN3, CCR5 and BCL2 as potential candidates to regulate the efficiency of Ca2+-dependent target cell killing.
In vitrocharacterisation and neurosteroid treatment of an N-Methyl-D-Aspartate receptor antibody-mediated seizure model
Authors: Wright Sukhvir K , Rosch Richard E , Wilson Max A , Upadhya Manoj A , Dhangar Divya R , Clarke-Bland Charlie , Wahid Tamara T , Barman Sumanta , Goebels Norbert , Kreye Jakob , Prüss Harald , Jacobson Leslie , Bassett Danielle S , Vincent Angela , Greenhill Stuart D , Woodhall Gavin L
Published: December 2020

Seizures are a prominent feature in N-Methyl-D-Aspartate receptor antibody (NMDAR-Ab) encephalitis, a distinct neuro-immunological disorder in which specific human autoantibodies bind and crosslink the surface of NMDAR proteins thereby causing internalization and a state of NMDAR hypofunction. To further understand ictogenesis in this disorder, and to test a novel treatment compound, we developed an NMDAR-Ab mediated rat seizure model that displays spontaneous epileptiform activityin vivoandin vitro. Using a combination of electrophysiological and dynamic causal modelling techniques we show that, contrary to expectation, reduction of synaptic excitatory, but not inhibitory, neurotransmission underlies the ictal events through alterations in the dynamical behaviour of microcircuits in brain tissue. Moreover,in vitroapplication of an NMDAR-specific neurosteroid, pregnenolone sulfate, that upregulates NMDARs, reduced established ictal activity. This proof-of-concept study highlights the complexity of circuit disturbances that may lead to seizures and the potential use of receptor-specific treatments in antibody-mediated seizures and epilepsy.
GABA relates to functional connectivity changes and retention in visuomotor adaptation
Authors: Nettekoven Caroline , Brady Sinead , Clarke William T , Emir Uzay , Levenstein Jacob , Petitet Pierre , Panouilleres Muriel T N , Bachtiar Velicia , O’Shea Jacinta , Johansen-Berg Heidi , Jenkinson Ned , Stagg Charlotte
Published: December 2020

Motor adaptation is fundamental to maintaining accurate movements under changing conditions, but the neurochemical basis of human motor adaptation is not well understood. Here, we used an ultra-high-field MR multimodal acquisition to address the hypothesis that M1 GABA and M1-Cerebellar functional connectivity would relate to retention of adaptation, but not acquisition of adaptation. As such, we demonstrate higher baseline M1 [GABA] relates to greater retention but does not relate to adaptation-acquisition. This relationship is mediated by change in M1-Cerebellar functional connectivity: higher M1 [GABA] relates to a decreased M1-Cerebellar connectivity, resulting in greater retention. These findings showed anatomical, neurochemical and behavioural specificity: As expected, no relationship was found between retention and a control metabolite, retention and connectivity change between control regions and between M1 [GABA] and behaviour in a control condition. The implication of a mechanistic link from neurochemistry to retention advances our understanding of population variability in retention and provides a step towards therapeutic interventions to restore motor abilities.
Unearthing the genes of plant-beneficial marine yeast -Wickerhamomyces anomalusstrain MSD1
Authors: Krishnan S Radhesh , Prabhakaran N , Ragunath K Sengali , Srinivasan R , Ponni K Keerthana , Balaji G , Gracy M , Brindha C , Narayanan Lakshmi , Latha K
Published: December 2020

Thede novogenome of unique marine yeast,Wickerhamomyces anomalusisolated from seaweed along Indian coast is presented. The genome assembly was carried out using MaSurCA assembler that generated a data size ∼14.3 mb from short and long reads obtained from Illumina Hiseq 4000 and GridION-X5 respectively. This assembled genome data were used for predicting genes using Augustus gene prediction tool that reported 6720 genes and proteins. The gene sequences were used to unravel the metabolic pathway analysis using KAAS database. The protein sequences were used for secondary analysis to predict the presence of signal peptides using SignalP tool, predicting protein family, domains using Pfam tool and prediction of transmembrane helices in proteins using TMHMM tool. Presence of genes involved in plant growth–promotion and regulation (PGPR) including siderophore and IAA production, iron and sulfur transformation, zinc and phosphate solubilization, nitrogen fixation, synthesis of anti-bacterial and volatile organic compound (VOCs), were assigned. Additionally, acid and alkaline phosphatases, ACC deaminases and lytic enzymes such as β-glucanases, proteases and chitinases involved in pathogen suppression, are also reported. The study elucidates comprehensive understanding of PGP attributes of MSD1 and its potential use in agriculture as bio-fertilizer /bio-stimulant.
scClassifR: Framework to accurately classify cell types in single-cell RNA-sequencing data
Authors: Nguyen Vy , Griss Johannes
Published: December 2020

Motivation

Automatic cell type identification in scRNA-seq datasets is an essential method to alleviate a key bottleneck in scRNA-seq data analysis. While most existing tools show good sensitivity and specificity in classifying cell types, they often fail to adequately not-classify cells that are not present in the used reference.

Results

scClassifR is a novel R package that provides a complete framework to automatically classify cells in scRNA-seq datasets. It supports both Seurat and Bioconductor’s SingleCellExperiment and is thereby compatible with the vast majority of R-based analysis workflows. scClassifR uses hierarchically organised SVMs to distinguish a specific cell type versus all others. It shows comparable or even superior sensitivity and specificity compared to existing tools while being robust in not-classifying unknown cell types. As a unique feature, it reports ambiguous cell assignments, including the respective probabilities. Finally, scClassifR provides dedicated functions to train and evaluate classifiers for additional cell types.

Availability and Implementation

scClassifR is freely available on GitHub (https://github.com/grisslab/scClassifR).
The evolutionary assembly of forest communities along environmental gradients: recent diversification or sorting of pre-adapted clades?
Authors: Linan Alexander G. , Myers Jonathan A. , Edwards Christine E. , Zanne Amy E. , Smith Stephen A. , Arellano Gabriel , Cayola Leslie , Farfan-Ríos William , Fuentes Alfredo F. , Garcia-Cabrera Karina , Gonzales-Caro Sebastián , Loza M. Isabel , Macía Manuel J. , Malhi Yadvinder , Nieto-Ariza Beatriz , Revilla Norma Salinas , Silman Miles , Tello J. Sebastián
Published: December 2020

Biogeographic events occurring in the deep past can contribute to the structure of modern ecological communities. However, little is known about how the emergence of environmental gradients shape the evolution of species that underlie community assembly. In this study, we address how the creation of novel environments lead to community assembly via two non-mutually exclusive processes: 1) the immigration and ecological sorting of pre-adapted clades (ISPC), and 2) recent adaptive diversification (RAD). We study these processes in the context of the elevational gradient created by the uplift of the Central Andes.

We develop a novel approach and method based on the decomposition of species turnover into within- and among-clade components, where clades correspond to lineages that originated before mountain uplift. Effects of ISPC and RAD can be inferred from how components of turnover change with elevation. We test our approach using data from over 500 Andean forest plots.

We found that species turnover between communities at different elevations is dominated by the replacement of clades that originated before the uplift of the Central Andes.

Our results suggest that immigration and sorting of clades pre-adapted to montane habitats is the primary mechanism shaping communities across elevations.
Elucidation of the molecular interactions that enable stable assembly and structural diversity in multicomponent immune receptors
Authors: Fong Lam-Kiu , Chalkley Matthew J. , Tan Sophia K. , Grabe Michael , DeGrado William F.
Published: December 2020

Multi-component immune receptors are essential complexes in which distinct ligand-recognition and signaling subunits are held together by interactions between acidic and basic residues of their transmembrane helices. A 2-to-1 acidic to basic motif in the transmembrane domains of the subunits is necessary and sufficient to assemble these receptor complexes. Here, we study a prototype for these receptors, a DAP12-NKG2C 2:1 heterotrimeric complex, in which the two DAP12 subunits each contribute a single transmembrane Asp residue, and the NKG2C subunit contributes a Lys to form the complex. DAP12 can also associate with 20 other subunits using a similar motif. Here we use molecular dynamics simulations to understand the basis for the high affinity and diversity of interactions in this group of receptors. Simulations of the transmembrane helices with differing protonation states of the Asp-Asp-Lys triad identified a structurally stable interaction in which a singly protonated Asp-Asp pair forms a hydrogen-bonded carboxyl-carboxylate clamp that clasps onto a charged Lys sidechain. This polar motif was also supported by density functional theory and a Protein Data Bank-wide search. In contrast, the helices are dynamic at sites distal to the stable carboxyl-carboxylate clamp motif. Such a locally stable but globally dynamic structure is well-suited to accommodate the sequence and structural variations in the transmembrane helices of multi-component receptors, which mix and match subunits to create combinatorial functional diversity from a limited number of subunits. It also supports a signaling mechanism based on multi-subunit clustering rather than propagation of rigid conformational changes through the membrane.

SIGNIFICANCE

Receptors that separate ligand recognition and intracellular signaling into separate protein subunits are ubiquitous in immunity. These subunits mix and match to create combinatorial functional diversity. The transmembrane domains of these receptors assemble through the interaction between two acidic and one basic residue on different helices. Using computational methods to study the DAP12-NKG2C receptor complex we identified a polar motif in which a singly protonated Asp-Asp pair forms a carboxyl-carboxylate clamp that clasps a charged Lys sidechain in the membrane. This local interaction allows dynamic variations in other regions of the helices that tolerate sequence diversity of the interacting subunits in this class of receptors, which signal through multi-subunit clustering rather than propagation of rigid conformational changes through the membrane.
Fructose 1,6-bisphosphate sensing by pyruvate kinase isozymes M2 (PKM2) controls MyoD stability and myogenic differentiation
Authors: Kim Minchul , Zhang Yao , Birchmeier Carmen
Published: December 2020

Glucose exerts beneficial effects on myogenesis and muscle physiology. However, the mechanisms by which glucose regulates myogenesis remain ill-defined or incompletely understood. Here, we show that low glycolysis destabilizes MyoD protein, a master myogenic transcription factor. Intriguingly, MyoD is not controlled by the cellular energy status per se, but by the level of fructose 1,6-bisphosphate, an intermediate metabolite of glycolysis. Fructose 1,6-bisphosphate is sensed by pyruvate kinase M2 (PKM2). In the presence of fructose 1,6-bisphosphate, PKM2 form tetramers that sequester the Huwe1 E3 ubiquitin ligase to the cytoplasm. Reduced fructose 1,6-bisphosphate levels dissociate the tetramer, releasing Huwe1 into the nucleus where it targets MyoD for degradation. Genetic or pharmacological modulation of PKM2-Huwe1 axis restores myogenic differentiation in glucose restricted conditions. Our results show that glucose metabolism directly regulates protein stability of a key myogenic factor and provide a rationale for enhancing myogenesis.
Cytosolic localization andin vitroassembly of humande novothymidylate synthesis complex
Authors: Spizzichino Sharon , Boi Dalila , Boumis Giovanna , Lucchi Roberta , Liberati Francesca Romana , Capelli Davide , Montanari Roberta , Pochetti Giorgio , Paone Alessio , Rinaldo Serena , Contestabile Roberto , Paiardini Alessandro , Tramonti Angela , Giardina Giorgio , Cutruzzolà Francesca
Published: December 2020

De novothymidylate synthesis is a crucial pathway for normal and cancer cells. Deoxythymidine monophosphate (dTMP) is synthesized by the combined action of three enzymes: serine hydroxymethyltransferase (SHMT), dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS), the latter two targets of widely used chemotherapeutics such as antifolates and 5-fluorouracil. These proteins translocate to the nucleus after SUMOylation and are suggested to assemble in this compartment into the thymidylate synthesis complex (dTMP-SC). We report the intracellular dynamics of the complex in lung cancer cells byin situproximity ligation assay, showing that it is also detected in the cytoplasm. This result strongly indicates that the role of the dTMP-SC assembly may go beyond dTMP synthesis. We have successfully assembled the dTMP synthesis complexin vitro, employing tetrameric SHMT1 and a bifunctional chimeric enzyme comprising human TYMS and DHFR. We show that the SHMT1 tetrameric state is required for efficient complex assembly, indicating that this aggregation state is evolutionary selected in eukaryotes to optimize protein-protein interactions. Lastly, our results on the activity of the complete thymidylate cyclein vitro, may provide a useful tool to develop drugs targeting the entire complex instead of the individual components.
Diffusion-controlled and `diffusionless' crystal growth: relation between liquid dynamics and growth kinetics of griseofulvin
Authors: Li Fang , Xin Junbo , Shi Qin
Published: December 2020

Understanding how liquid dynamics govern crystallization is critical for maintaining the physical stability of amorphous pharmaceutical formulations. In the present study, griseofulvin (GSF), a classic antifungal drug, was used as the model system to investigate the correlations between crystal growth kinetics and liquid dynamics. The temperature dependence of the kinetic part of the bulk crystal growth in a supercooled liquid of GSF was weaker than that of the structural relaxation time τα and scaled as τα
−0.69. In the glassy state, GSF exhibited the glass-to-crystal (GC) growth behavior, whose growth rate was too fast to be under the control of the α-relaxation process. Moreover, from the perspective of τα, the GC growth of GSF also satisfied the general condition for GC growth to exist: D/u < 7 pm, where D is the diffusion coefficient and u the speed of crystal growth. Also compared were the fast surface crystal growth rates u
s and surface relaxation times τsurface predicted by the random first-order transition theory. Here, the surface crystal growth rate u
s of GSF exhibited a power-law dependence upon the surface structural relaxation time: u
s ∝ τsurface
−0.71, which was similar to that of the bulk growth rate and τα. These findings are important for understanding and predicting the crystallization of amorphous pharmaceutical solids both in the bulk and at the surface.
µDrop: a system for high-throughput small-angle X-ray scattering measurements of microlitre samples
Authors: Haider Richard , Sartori Barbara , Radeticchio Andrea , Wolf Marcell , Dal Zilio Simone , Marmiroli Benedetta , Amenitsch Heinz
Published: December 2020

An automatic sample changer system for measurements of large numbers of liquid samples – the µDrop Sample Changer – is presented. It is based on a robotic arm equipped with a pipetting mechanism, which is combined with a novel drop-based sample holder. In this holder a drop of liquid is suspended between two parallel plates by surface tension. The absence of a transfer line benefits the cleaning, improving the background as well as making it faster and more efficient than most comparable capillary-based systems. The µDrop Sample Changer reaches cycle times below 35 s and can process up to 480 samples in a single run. Sample handling is very reliable, with a drop misplacement chance of about 0.2%. Very low sample volumes (<20 µl) are needed and repeatable measurements were performed down to 6 µl. Using measurements of bovine serum albumin and lysozyme, the performance of the instrument and quality of the gathered data of low and high concentrations of proteins are presented. The temperature of samples can also be controlled during storage and during measurement, which is demonstrated by observing a phase transition of a mesophase-forming lipid solution. The instrument has been developed for use in small-angle X-ray scattering experiments, which is a well established technique for measuring (macro-)molecules. It is commonly used in biological studies, where often large sets of rare samples have to be measured.
A multivariate grain size and orientation distribution function: derivation from electron backscatter diffraction data and applications
Authors: Galán López Jesús , Kestens Leo A. I.
Published: December 2020

Two of the microstructural parameters most influential in the properties of polycrystalline materials are grain size and crystallographic texture. Although both properties have been extensively studied and there are a wide range of analysis tools available, they are generally considered independently, without taking into account the possible correlations between them. However, there are reasons to assume that grain size and orientation are correlated microstructural state variables, as they are the result of single microstructural formation mechanisms occurring during material processing. In this work, the grain size distribution and orientation distribution functions are combined in a single multivariate grain size orientation distribution function (GSODF). In addition to the derivation of the function, several examples of practical applications to low carbon steels are presented, in which it is shown how the GSODF can be used in the analysis of 2D and 3D electron backscatter diffraction data, as well as in the generation of representative volume elements for full-field models and as input in simulations using mean-field methods.
Emissions prediction of an aero-piston gasoline engine during surveillance flight of an unmanned aerial vehicle
Authors: Dinc Ali , Otkur Murat
Published: December 2020

Purpose

The purpose of this study is to perform the preliminary design, flight performance and exhaust emissions calculations of a piston engine powered unmanned aerial vehicle (UAV) during a flight cycle which consists of multiple flight altitudes and airspeeds.

Design/methodology/approach

A genuine computer model in Matlab/Simulink was developed to predict the size and weight of UAV and piston engine (using Avgas 100LL fuel) performance together with exhaust emissions in an iterative process.

Findings

The amount of emitted exhaust gases including carbon dioxide, carbon monoxide, hydrocarbons and nitrogen oxides were calculated in a typical UAV mission profile as a whole and also divided into mission flight segments.

Research limitations/implications

Emissions were calculated based on fuel flow and engine speed inputs based on ground test data for emission indices. Test data for emission indices was very limited.

Practical implications

As UAV utilization has been increasing around the world, this study presents important and noticeable results on the emissions that need to be considered for environmental purposes.

Originality/value

In literature, emission prediction studies for UAVs are very rare. In fact, UAVs typically have quite different flight speeds and altitudes than regular manned aircraft and emissions change with speed and altitude. Additionally, unlike manned aircraft, UAVs can fly more than 24 h with different operation characteristics. The originality of this study presents the emission predictions of a piston engine UAV which flies with a significantly different mission profile than a manned aircraft.
Quality of gluten-free cookies made with rice flour of different levels of amylose and cowpea beans
Authors: Dierings de Souza Estefania Julia , Pereira Aline Machado , Fontana Mauro , Vanier Nathan Levien , Gularte Marcia Arocha
Published: December 2020

Purpose

The objective of this study was to evaluate the effects of rice flour obtained from rice grains with different levels of amylose on technological, nutritional and sensory properties of cookies made with a blend of rice and cowpea flour.

Design/methodology/approach

The cookies preparation was set at a ratio of rice flour and cowpea beans 70:30. The studied formulations were: LA: low amylose rice flour; MA: medium-amylose rice flour; HA: high amylose rice flour. The quality of the obtained cookies was analyzed for proximate composition, in vitro protein digestibility, thickness, diameter, dispersion factor, texture, color, amino acid profile and sensory properties.

Findings

Proximate composition and in vitro protein digestibility showed no differences between the three studied formulations. The medium and low amylose rice flour cookies showed the lowest hardness values. The combination of rice and beans allowed a good balance of essential amino acids. The cookies formulated with high amylose rice flour presented lighter coloration, low hardness and greater sensory preference.

Originality/value

Rice and cowpea flours are an alternative source for the preparation of gluten-free bakery products, such as cookies. The high amylose content of rice flour has less negative interference in the texture characteristics of the cookies. The combination of rice and beans flour provides a balance of essential amino acids.
Banking sector earnings management using loan loss provisions in the Fintech era
Authors: Ozili Peterson K.
Published: December 2020

Purpose

This paper analyzes banking sector earnings management using loan loss provisions (LLPs) in the Fintech era.

Design/methodology/approach

Regression methodology was used to examine earnings management in the Fintech era.

Findings

The findings show evidence for bank income smoothing using LLPs. There is greater income smoothing in the second-wave Fintech era compared to the first-wave Fintech era, and the presence of strong institutions did not lower income smoothing in the second-wave era. Bank income smoothing is also greater in (1) Bank of International Settlement (BIS) and EU countries than in non-EU countries and G7 countries, (2) well-capitalized banking sectors and (3) during economic booms in the second-wave Fintech era.

Practical implications

The competition for loans and deposits by banks and Fintech lenders in the second-wave Fintech era created additional incentives for banks to engage in income smoothing to report competitive and stable earnings.

Originality/value

The study uses a unique approach to detect country-level earnings management in the banking sector. Also, this study extends the bank earnings management literature by introducing the Fintech era as a determinant of the extent of bank earnings management.