bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin aging risk factors: A nationwide population study in Mongolia Risk factors of skin aging
Authors: Nanzadsuren Tuya , Myatav Tuul , Dorjkhuu Amgalanbaatar , Ganbat Mandukhai , Batbold Chuluunbileg , Batsuuri Baljinnyam , Byamba Khandsuren
Published: March 2021

The world population is aging and no country is immune to the consequences. We are not aware of any country-specific skin aging risk factors data for the Mongolian people. Thus, we aimed to study the risk factors associated with skin aging in the Mongolian population. A population-based cross-sectional study of 2720 study participants 18 years of age and older was performed evaluating the severity of skin aging based on cutaneous microtopography. Questionnaire data and skin physiological measurements were obtained. The odds ratios for skin aging grades associated with risk factors were estimated using ordinal logistic regression. Study participant’s mean age was 45 years, ranging from 18 to 87. After adjustment for known risk factors, skin aging was associated with demographic risk factors such as increasing age (aOR=1.19, 95% CI 1.18-1.20), living in an urban area (aOR=1.31, 95% CI 1.12-1.55) and working outside (aOR=1.44, 95% CI 0.88-2.39) and lifestyle factors including non-usage of sunscreen cream (aOR=1.09 95% CI 0.87-1.37), being a smoker (aOR=1.32, 95% CI 1.09-1.61), having a higher body mass index (BMI) (aOR=1.04, 95% CI 1.02-1.06) and higher levels of sun exposure time (aOR=1.03, 95% CI 1.00-1.06) were significantly associated with higher skin aging grades. Having dry (aOR=1.94, 95% CI 1.45-2.59) and combination skin (aOR=1.62, 95% CI 1.22-2.16) types were also independent risk factors associated with skin aging. Having very low skin surface moisture at the T-zone (aOR=2.10, 95% CI 1.42-3.11) and U-zone (aOR=1.25, 95% CI 0.95-1.65) were significantly related to skin aging. Older age, urban living, harsh working conditions, living in a ger district were independent demographic risk factors related to skin aging. Not using sunscreen cream, smoking, higher BMI, greater levels of sun exposure were significant lifestyle risk factors. Having a skin type other than normal was a physiologic risk factor for skin aging.
Neurexin and Frizzled intercept axonal-transport at microtubule minus-ends to control synapse formation
Authors: Balseiro-Gómez Santiago , Park Junhyun , Yue Yang , Ding Chen , Shao Lin , Ҫetinkaya Selim , Kuzoian Caroline , Hammarlund Marc , Verhey Kristen J , Yogev Shaul
Published: March 2021

Precise synaptic connectivity defines neuronal circuits. Synapse formation is locally determined by transmembrane proteins, yet synaptic material is synthesized remotely and undergoes processive transport in axons. How local synaptogenic signals intercept synaptic cargo in transport to promote its delivery and synapse formation is unknown. We found that control of synaptic cargo delivery at microtubule (MT) minus-ends mediates pro- and anti-synaptogenic activities of presynaptic Neurexin and Frizzled inC. elegans, and identified the atypical kinesin VAB-8/KIF26 as a key molecule in this process. VAB-8/KIF26 levels at synaptic MT minus-ends are controlled by Frizzled and Neurexin, its loss mimics neurexin mutants or Frizzled hyperactivation, and its overexpression can rescue synapse-loss in these backgrounds. VAB-8/KIF26 is required for the synaptic localization of other minus-end proteins and promotes pausing of retrograde transport to allow delivery to synapses. Consistently, reducing retrograde transport rescues synapse-loss invab-8and neurexin mutants. These results uncover an important mechanistic link between synaptogenic signaling and axonal transport.
Nanoscale Lubrication in Biosystems as Rationalized in Terms of Fractons and Spectral-Mechanical Properties of Networked Biopolymers in Ionic Solutions
Authors: Gadomski A. , Bełdowski P.
Published: March 2021

Articular cartilage is a natural tribochemical device just-designed by nature. Yet, a vivid debate goes on toward the mechanisms by which its nanoscopic viscoelastic properties facilitate lubrication in terms of ultralow static and kinetic friction coefficients. In this concisely conducted conceptual discussion, we wish to point out that a nanoscale tribomechanistic description based upon certain “viscoelastic quanta”, called fractons, expressing spectral-mechanical properties of viscoelastic nets under the influence of force/pressure factor(s), may contribute substantially to the elucidation of ultralow coefficients of friction in the articular cartilage of predictable relaxational response. Our example unveils a part of a mechanically responsive viscoelastic network, such as a tied piece of hyaluronan molecule, fit in an Edwards type tube, in which upon water–mediated interaction of lipids with the hyaluronan when subjected to loading at the nanoscale, consecutive stress-field and ion diffusion actions occur simultaneously. It results in a natural-logarithmic formula that interrelates a number of hyaluronan’s interactive residues,N, with certain molecular-elastic (an exponentγ) and surface-to-volume (nano-colloid type) characteristics of around 2/3 to emerge near thermodynamic equilibrium, that is to say after a frictional loading action performed. It enables to relate uniquely a value of the exponent 0 <γ< 1/2 with a virtual tribomicellization scenario of the nanoscale friction–lubrication event accompanied by inevitable tubular-milieu viscosity alterations at criticality when the quasi-static friction scenario shows up, preferably withγ→ 1/3 from above for large enoughN–s. A periodic vibrational super-biopolymer’s mode is exploited, leading to a change in the nanoscale friction-lubrication period from which an opportunity to involve an essential contribution to the (nanoscale) coefficient of friction arises.

PACS numbers

71.10.+x, 81.30.Fb, 05.70.Fh, 05.60.+w
Temporal filtering of luminance and chromaticity in macaque visual cortex
Authors: Horwitz Gregory D.
Published: March 2021

The visibility of a periodic light modulation depends on its temporal frequency and spectral properties. Contrast sensitivity is highest at 8–10 Hz for modulations of luminance but is substantially lower for modulations between equiluminant lights. This difference between luminance and chromatic contrast sensitivity is rooted in retinal filtering, but additional filtering occurs in the cerebral cortex. To measure the cortical contributions to luminance and chromatic temporal contrast sensitivity, signals in the lateral geniculate nucleus (LGN) were compared to the behavioral contrast sensitivity of macaque monkeys. Long wavelength-sensitive (L) and medium wavelength-sensitive (M) cones were modulated in phase, to produce a luminance modulation (L+M), or in counterphase, to produce a chromatic modulation (L-M). The sensitivity of LGN neurons was well matched to behavioral sensitivity at low temporal frequencies but was approximately 7 times greater at high temporal frequencies. Similar results were obtained for L+M and L-M modulations. These results show that differences in the shapes of the luminance and chromatic temporal contrast sensitivity functions are due almost entirely to pre-cortical mechanisms. Simulations of cone photoreceptor currents show that temporal information loss in the retina and at the retinogeniculate synapse exceeds cortical information loss under most of the conditions tested.
Broad decline and subsequent differential re-emergence of respiratory viruses during COVID-19 pandemic response measures, Singapore 2020
Authors: Wan Wei Yee , Thoon Koh Cheng , Loo Liat Hui , Chan Kian Sing , Oon Lynette L. E. , Ramasamy Adaikalavan , Maiwald Matthias
Published: March 2021

Importance

COVID-19 pandemic control measures affect the prevalence of other respiratory viruses. Effects on some viruses have been described; however, the broader impact and temporal relationship of control measures on virus decline and subsequent re-emergence have not been thoroughly documented. Understanding these phenomena may influence health policies.

Objective

To examine the prevalence of unrelated respiratory viruses in relation to population-wide pandemic response measures and phases in 2020 in Singapore.

Design, Setting, and Participants

Data from respiratory multiplex PCRs from 3 major hospitals (total 3700 beds) in Singapore were collated. The full dataset consisted of 42,558 test results, 19,898 from 2019 and 22,660 from 2020.

Main Outcomes and Measures

Weekly virus prevalence data were mapped onto prevailing pandemic response measures, in order to elucidate temporal relationships and differential virus responses. Pre-pandemic data from 2019 were compared with data from 2020.

Results

Early response measures, even before national lockdown, were followed by a dramatic reduction of influenza viruses and a more gradual decline of other respiratory viruses, including respiratory syncytial virus, parainfluenza viruses, endemic coronaviruses and metapneumovirus. Marked decline of enterovirus/rhinovirus and adenovirus, however, was only observed during lockdown. About 13 weeks into phased reopening, enterovirus/rhinovirus re-emerged, followed by adenovirus, the latter mainly in the pediatric population. All other viruses remained at low levels until the end of 2020.

Conclusions and Relevance

COVID-19 control measures in Singapore had a significant impact on a broad range of respiratory viruses. Effects of various control measures varied between phases and different viruses. Influenza viruses declined earliest and most dramatically; relaxation of measures was followed by re-emergence of enterovirus/rhinovirus and adenovirus. These patterns are presumably a result of different propensities for contact versus droplet and overall ease of transmission, and different virus reservoirs. Further studies into these phenomena are a matter of public health importance.

Key Points

Question

What were the effects of COVID-19 pandemic control measures in Singapore on the prevalence of other respiratory viruses?

Findings

Viruses responded differently to control measures. Influenza viruses declined rapidly after early control measures and remained near-absent during reopening after lockdown. Enterovirus/rhinovirus and adenovirus declined later and re-emerged earlier than other viruses during phased reopening.

Meaning

Population-wide interventions resulted in a broad decline and subsequent differential re-emergence of non-targeted respiratory viruses, corresponding to different patterns of virus response to control measures.
Overexpression-based detection of translatable circular RNAs is vulnerable to coexistent linear RNA byproducts
Authors: Jiang Yanyi , Chen Xiaofan , Zhang Wei
Published: March 2021

In RNA field, the demarcation between coding and non-coding has been negotiated by the recent discovery of occasionally translated circular RNAs (circRNAs). Although absent of 5’ cap structure, circRNAs can be translated cap-independently. Complementary intron-mediated overexpression is one of the most utilized methodologies for circRNA research but not without bearing echoing skepticism for its poorly defined mechanism and latent coexistent side products. In this study, leveraging such circRNA overexpression system, we have interrogated the protein-coding potential of 30 human circRNAs containing infinite open reading frames in HEK293T cells. Surprisingly, pervasive translation signals are detected by immunoblotting. However, intensive mutagenesis reveals that numerous translation signals are generated independently of circRNA synthesis. We have developed a dual tag strategy to isolate translation noise and directly demonstrate that the fallacious translation signals originate from cryptically spliced linear transcripts. The concomitant linear RNA byproducts, presumably concatemers, can be translated to allow pseudo rolling circle translation signals, and can involve backsplicing junction (BSJ) to disqualify the BSJ-based evidence for circRNA translation. We also find non-AUG start codons may engage in the translation initiation of circRNAs. Taken together, our systematic evaluation sheds light on heterogeneous translational outputs from circRNA overexpression vector and comes with a caveat that ectopic overexpression technique necessitates extremely rigorous control setup in circRNA translation and functional investigation.
On-off transition and ultrafast decay of amino acid luminescence driven by modulation of supramolecular packing
Authors: Arnon Zohar A. , Kreiser Topaz , Yakimov Boris , Brown Noam , Aizen Ruth , Shaham-Niv Shira , Makam Pandeeswar , Qaisrani Muhammad Nawaz , Poli Emiliano , Ruggiero Antonella , Slutsky Inna , Hassanali Ali , Shirshin Evgeny , Levy Davide , Gazit Ehud
Published: March 2021

It has been experimentally observed that various biomolecules exhibit clear luminescence in the visible upon aggregation, contrary their monomeric state. However, the physical basis for this phenomenon is still elusive. Here, we systematically examine all coded amino acids to provide non-biased insights into this phenomenon. Several amino acids, including non-aromatic, show intense visible luminescence. While lysine crystals display the highest signal, the very chemically similar non-coded ornithine does not, implying a role for molecular packing rather than the chemical characteristics of the molecule. Furthermore, cysteine show luminescence that is indeed crystal-packing-dependent as repeated rearrangements between two crystal structures result in a reversible on-off optical transition. In addition, ultrafast lifetime decay is experimentally validated, corroborating a recently raised hypothesis regarding the governing role of nπ* states in the emission formation. Collectively, our study supports the hypothesis that electronic interactions between molecules that are non-fluorescent and non-absorbing at the monomeric state may result in reversible optically-active states by the formation of supramolecular fluorophores.
Measuring splash-dispersal of a major wheat pathogen in the field
Authors: Karisto Petteri , Suffert Frédéric , Mikaberidze Alexey
Published: March 2021

Capacity for dispersal is a fundamental fitness component of plant pathogens. Empirical characterization of plant pathogen dispersal is of prime importance for understanding how plant pathogen populations change in time and space. We measured dispersal ofZymoseptoria triticiin natural environment. Primary disease gradients were produced by rain-splash driven dispersal and subsequent transmission via asexual pycnidiospores from infected source. To achieve this, we inoculated field plots of wheat (Triticum aestivum) with two distinctZ. triticistrains and a 50/50 mixture of the two strains. We measured effective dispersal of theZ. triticipopulation based on pycnidia counts using automated image analysis. The data were analyzed using a spatially-explicit mathematical model that takes into account the spatial extent of the source. We employed robust bootstrapping methods for statistical testing and adopted a two-dimensional hypotheses test based on the kernel density estimation of the bootstrap distribution of parameter values. Genotyping of re-isolated pathogen strains with strain-specific PCR-reaction further confirmed the conclusions drawn from the phenotypic data. The methodology presented here can be applied to other plant pathosystems.

We achieved the first estimates of the dispersal kernel of the pathogen in field conditions. The characteristic spatial scale of dispersal is tens of centimeters – consistent with previous studies in controlled conditions. Our estimation of the dispersal kernel can be used to parameterize epidemiological models that describe spatial-temporal disease dynamics within individual wheat fields. The results have the potential to inform spatially targeted control of crop diseases in the context of precision agriculture.
Decoding brain states on the intrinsic manifold of human brain dynamics across wakefulness and sleep
Authors: Rué-Queralt J. , Stevner A. , Tagliazucchi E. , Laufs H. , Kringelbach M. L. , Deco G. , Atasoy S.
Published: March 2021

Current state-of-the-art functional magnetic resonance imaging (fMRI) offers remarkable imaging quality and resolution, yet, theintrinsicdimensionality of brain dynamics in different states (wakefulness, light and deep sleep) remains unknown. Here we present a novel method to reveal the low dimensional intrinsic manifold underlying human brain dynamics, which is invariant of the high dimensional spatio-temporal representation of the neuroimaging technology. By applying this novelintrinsic manifoldframework to fMRI data acquired in wakefulness and sleep, we reveal the nonlinear differences between wakefulness and three different sleep stages, and successfully decode these different brain states with an average accuracy of 96%. Remarkably, a further group analysis shows that the intrinsic manifolds of all participants share a common topology. Overall, our results reveal the intrinsic manifold underlying the spatiotemporal dynamics of brain activity and demonstrate how this manifold enables the decoding of different brain states such as wakefulness and various sleep stages.
The unraveling of balanced complexes in metabolic networks
Authors: Langary Damoun , Küken Anika , Nikoloski Zoran
Published: March 2021

Balanced complexes in biochemical networks are at core of several theoretical and computational approaches that make statements about the properties of the steady states supported by the network. Recent computational approaches have employed balanced complexes to reduce metabolic networks, while ensuring preservation of particular steady-state properties; however, the underlying factors leading to the formation of balanced complexes have not been studied, yet. Here, we present a number of factorizations providing insights in mechanisms that lead to the origins of the corresponding balanced complexes. The proposed factorizations enable us to categorize balanced complexes into four distinct classes, each with specific origins and characteristics. They also provide the means to efficiently determine if a balanced complex in large-scale networks belongs to a particular class from the categorization. The results are obtained under very general conditions and irrespective of the network kinetics, rendering them broadly applicable across variety of network models. Application of the categorization shows that all classes of balanced complexes are present in large-scale metabolic models across all kingdoms of life, therefore paving the way to study their relevance with respect to different properties of steady states supported by these networks.

Highlights

Balanced complexes are ubiquitous in real-world networks, and facilitate insights in steady state flux phenotypes in large-scale metabolic networks.

Novel factorizations are proposed that explain the formation of balanced complexes and enable their categorization.

The results also provide a computationally-efficient tool for the identification of balanced complexes in large-scale networks.

Examination of metabolic network models across all kingdoms of life shows that all categories naturally arise in this type of networks.
Physical mechanisms of ESCRT-III-driven cell division in archaea
Authors: Harker-Kirschneck L. , Hafner A. E. , Yao T. , Pulschen A. , Hurtig F. , Vanhille-Campos C. , Hryniuk D. , Culley S. , Henriques R. , Baum B. , Šarić A.
Published: March 2021

Living systems propagate by undergoing rounds of cell growth and division. Cell division is at heart a physical process that requires mechanical forces, usually exerted by protein assemblies. Here we developed the first physical model for the division of archaeal cells, which despite their structural simplicity share machinery and evolutionary origins with eukaryotes. We show how active geometry changes of elastic ESCRT-III filaments, coupled to filament disassembly, are sufficient to efficiently split the cell. We explore how the non-equilibrium processes that govern the filament behaviour impact the resulting cell division. We show how a quantitative comparison between our simulations and dynamic data for ESCRTIII-mediated division inSulfolobus acidocaldarius, the closest archaeal relative to eukaryotic cells that can currently be cultured in the lab, and reveal the most likely physical mechanism behind its division.
Comparative genome analysis using sample-specific string detection in accurate long reads
Authors: Khorsand Parsoa , Denti Luca ,   Human Genome Structural Variant Consortium, Bonizzoni Paola , Chikhi Rayan , Hormozdiari Fereydoun
Published: March 2021

Motivation

Comparative genome analysis of two or more whole-genome sequenced (WGS) samples is at the core of most applications in genomics. These include discovery of genomic differences segregating in population, case-control analysis in common diseases, and rare disorders. With the current progress of accurate long-read sequencing technologies (e.g., circular consensus sequencing from PacBio sequencers) we can dive into studying repeat regions of genome (e.g., segmental duplications) and hard-to-detect variants (e.g., complex structural variants).

Results

We propose a novel framework for addressing the comparative genome analysis by discovery of strings that are specific to one genome (“samples-specific” strings). We have developed an accurate and efficient novel method for discovery of samples-specific strings between two groups of WGS samples. The proposed approach will give us the ability to perform comparative genome analysis without the need to map the reads and is not hindered by shortcomings of the reference genome. We show that the proposed approach is capable of accurately finding samples-specific strings representing nearly all variation (>98%) reported across pairs or trios of WGS samples using accurate long reads (e.g., PacBio HiFi data).

Availability

The proposed tool is publicly available athttps://github.com/Parsoa/PingPong.
Antimicrobial Resistance and Genomic Characterization of Salmonella Dublin Isolates in Cattle from the United States.
Authors: Srednik Mariela , Lantz Kristina , Hicks Jessica A , Morningstar-Shaw Brenda R , Mackie Tonya A , Schlater Linda K
Published: March 2021

Salmonella enterica subspecies enterica serovar Dublin is a host-adapted serotype in cattle, associated with enteritis and systemic disease. While rare in humans, it can cause severe illness, including bacteremia, with hospitalization and death. In the United States, S. Dublin has become one of the most multidrug-resistant serotypes . The objective of this study was to characterize S. Dublin isolates from sick cattle by analyzing phenotypic and genotypic antimicrobial resistance (AMR) profiles, the presence of plasmids, and phylogenetic relationships. S. Dublin isolates (n=140) were selected from submissions to the NVSL for Salmonella serotyping (2014 – 2017) from 21 states. Isolates were tested for susceptibility against 14 class-representative antimicrobial drugs. Resistance profiles were determined using the ABRicate with Resfinder and NCBI databases, AMRFinder and PointFinder. Plasmids were detected using ABRicate with PlasmidFinder. Phylogeny was determined using vSNP. We found 98% of the isolates were resistant to more than 4 antimicrobials . Only 1 isolate was pan-susceptible and had no predicted AMR genes. All S. Dublin isolates were susceptible to azithromycin and meropenem. They showed 96% resistance to sulfonamides, 97% to tetracyclines, 95% to aminoglycosides and 85% to beta-lactams . The most common AMR genes were: sulf2 and tetA (98.6%), aph(3'')-Ib and aph(6)-Id (96.4%), floR (94.3%), and blaCMY-2 (85.7%). All quinolone resistant isolates presented mutations in gyr A. Ten plasmid types were identified among all isolates with IncA/C2, IncX1, and IncFII(S) being the most frequent. The S. Dublin isolates show low genomic genetic diversity. This study provided antimicrobial susceptibility and genomic insight into S . Dublin clinical isolates from cattle in the U.S. Further sequence analysis integrating food and human origin S . Dublin isolates may provide valuable insight on increased virulence observed in humans.
Cell-to-cell and type-to-type heterogeneity of signaling networks: Insights from the crowd
Authors: Gabor Attila , Tognetti Marco , Driessen Alice , Tanevski Jovan , Guo Baosen , Cao Wencai , Shen He , Yu Thomas , Chung Verena ,   Single Cell Signaling in Breast Cancer DREAM Consortium members, Bodenmiller Bernd , Saez-Rodriguez Julio
Published: March 2021

Recent technological developments allow us to measure the status of dozens of proteins in individual cells. This opens the way to understand the heterogeneity of complex multi-signaling networks across cells and cell-types, with important implications to understand and treat diseases such as cancer. These technologies are however limited to proteins for which antibodies are available and are fairly costly, making predictions of new markers and of existing markers under new conditions a valuable alternative. To assess our capacity to make such predictions and boost further methodological development, we organised the Single Cell Signaling in Breast Cancer DREAM challenge. We used a mass cytometry data set, covering 36 markers in over 4,000 conditions totalling 80 million single cells across 67 breast cancer cell lines. Through four increasingly difficult subchallenges, the participants predicted missing markers, new conditions, and the time course response of single cells to stimuli in the presence and absence of kinase inhibitors. The challenge results show that despite the stochastic nature of signal transduction in single cells, the signaling events are tightly controlled and machine learning methods can accurately predict new experimental data.

Graphical Abstract

Key points

Over 80 million single-cell multiplexed measurements across 67 cell lines, 54 conditions and 10 time points to benchmark predictive models of single cell signaling

73 approaches from 27 teams for predicting response to kinase inhibitors on single cell level, and dynamic response from unperturbed basal omics data

Predictions of single marker models correlate with measurements with a correlation coefficient of 0.76

Top models of whole signaling response models perform almost as well as a biological replicate

Cell-line specific variation in dynamics can be predicted from basal omics
Pan-genomic Matching Statistics for Targeted Nanopore Sequencing
Authors: Ahmed Omar , Rossi Massimiliano , Kovaka Sam , Schatz Michael C. , Gagie Travis , Boucher Christina , Langmead Ben
Published: March 2021

Nanopore sequencing is an increasingly powerful tool for genomics. Recently, computational advances have allowed nanopores to sequence in a targeted fashion; as the sequencer emits data, software can analyze the data in real time and signal the sequencer to eject “non-target” DNA molecules. We present a novel method called SPUMONI, which enables rapid and accurate targeted sequencing with the help of efficient pangenome indexes. SPUMONI uses a compressed index to rapidly generate exact or approximate matching statistics (half-maximal exact matches) in a streaming fashion. When used to target a specific strain in a mock community, SPUMONI has similar accuracy as minimap2 when both are run against an index containing many strains per species. However SPUMONI is 12 times faster than minimap2. SPUMONI’s index and peak memory footprint are also 15 to 4 times smaller than minimap2, respectively. These improvements become even more pronounced with even larger reference databases; SPUMONI’s index size scales sublinearly with the number of reference genomes included. This could enable accurate targeted sequencing even in the case where the targeted strains have not necessarily been sequenced or assembled previously. SPUMONI is open source software available fromhttps://github.com/oma219/spumoni.
In vivotissue-specific chromatin profiling inDrosophila melanogasterusing GFP-tagged nuclei
Authors: Jauregui-Lozano Juan , Bakhle Kimaya , Weake Vikki M.
Published: March 2021

Abstract

The chromatin landscape defines cellular identity in multicellular organisms with unique patterns of DNA accessibility and histone marks decorating the genome of each cell type. Thus, profiling the chromatin state of different cell types in an intact organism under disease or physiological conditions can provide insight into how chromatin regulates cell homeostasisin vivo. To overcome the many challenges associated with characterizing chromatin state in specific cell types, we developed an improved approach to isolateDrosophilanuclei tagged with GFP expressed under Gal4/UAS control. Using this protocol, we profiled chromatin accessibility using Omni-ATAC, and examined the distribution of histone marks using ChIP-seq and CUT&Tag in adult photoreceptor neurons. We show that the chromatin landscape of photoreceptors reflects the transcriptional state of these cells, demonstrating the quality and reproducibility of our approach for profiling the transcriptome and epigenome of specific cell types inDrosophila.
Reward boosts reinforcement-based motor learning
Authors: Vassiliadis Pierre , Derosiere Gerard , Dubuc Cecile , Lete Aegryan , Crevecoeur Frederic , Hummel Friedhelm C , Duque Julie
Published: March 2021

Besides relying heavily on sensory and reinforcement feedback, motor skill learning may also depend on the level of motivation experienced during training. Yet, how motivation by reward modulates motor learning remains unclear. In 90 healthy subjects, we investigated the net effect of motivation by reward on motor learning while controlling for the sensory and reinforcement feedback received by the participants. Reward improved motor skill learning beyond performance-based reinforcement feedback. Importantly, the beneficial effect of reward involved a specific potentiation of reinforcement-related adjustments in motor commands, which concerned primarily the most relevant motor component for task success and persisted on the following day in the absence of reward. We propose that the long-lasting effects of motivation on motor learning may entail a form of associative learning resulting from the repetitive pairing of the reinforcement feedback and reward during training, a mechanism that may be exploited in future rehabilitation protocols.
BubbleGun: Enumerating Bubbles and Superbubbles in Genome Graphs
Authors: Dabbaghie Fawaz , Ebler Jana , Marschall Tobias
Published: March 2021

Motivation

With the fast development of third generation sequencing machines,de novogenome assembly is becoming a routine even for larger genomes. Graph-based representations of genomes arise both as part of the assembly process, but also in the context ofpangenomesrepresenting a population. In both cases, polymorphic loci lead tobubblestructures in such graphs. Detecting bubbles is hence an important task when working with genomic variants in the context of genome graphs.

Results

Here, we present a fast general-purpose tool, calledBubbleGun, for detecting bubbles and superbubbles in genome graphs. Furthermore,BubbleGundetects and outputs runs of linearly connected bubbles and superbubbles, which we callbubble chains. We showcase its utility on de Bruijn graphs and compare our results tovg’s snarl detection. We show thatBubbleGunis considerably faster thanvgespecially in bigger graphs, where it reports all bubbles in less than 30 minutes on a human sample de Bruijn graph of around 2 million nodes.

Availability

BubbleGunis available and documented athttps://github.com/fawaz-dabbaghieh/bubble_gununder MIT license.

Contact

fawaz@hhu.deortobias.marschall@hhu.de

Supplementary information

Supplementary data are available atBioinformaticsonline.
PIMBA: a PIpeline for MetaBarcoding Analysis
Authors: Oliveira Renato R. M. , Silva Raíssa , Nunes Gisele L. , Oliveira Guilherme
Published: March 2021

DNA metabarcoding is an emerging monitoring method capable of assessing biodiversity from environmental samples (eDNA). Advances in computational tools have been required due to the increase of Next-Generation Sequencing data. Tools for DNA metabarcoding analysis, such as MOTHUR, QIIME, Obitools, and mBRAVE have been widely used in ecological studies. However, some difficulties are encountered when there is a need to use custom databases. Here we present PIMBA, a PIpeline for MetaBarcoding Analysis, which allows the use of customized databases, as well as other reference databases used by the softwares mentioned here. PIMBA is an open-source and user-friendly pipeline that consolidates all analyses in just three command lines.

Availability and Implementation

https://github.com/reinator/pimba

Contact

renato.renison@gmail.comandguilherme.oliveira@pq.itv.org.
Mycobacterium tuberculosismodifies cell wall carbohydrates during biofilm growth with a concomitant reduction in complement activation
Authors: Keating Thomas , Lethbridge Samuel , Thomas Stephen R. , Alderwick Luke J. , Taylor Stephen C. , Bacon Joanna
Published: March 2021

There is an urgent need for drugs, new vaccines, and diagnostics for TB. It is recognised that research needed for the development of new vaccines for TB needs to be underpinned by understanding both the molecular and cellular mechanisms of host-pathogen interactions and how the immune response can be modulated to achieve protection with the use of a new vaccine for TB. Complement interacts with and orchestrates many aspects of the innate and adaptive immune responses and activation byMycobacterium tuberculosiscan be triggered by all three pathways. However, little is known about the contribution of each of these pathways during TB disease, particularly with respect to mycobacterial phenotype. There is strong evidence for extracellular communities ofM. tuberculosisduring TB disease (biofilms) that are found in the acellular rim of granulomas. These biofilms have been observed in cavities in lung resections from TB patients and are likely to be present in post-primary TB episodes in necrotic lesions. Our study aimed to understand more about the interactions betweenM. tuberculosisbiofilms and complement activation, to determine which mycobacterial cell wall components are altered during biofilm growth, and how their alteration contributes to modulation of the complement response. We show that the lectin pathway has a reduced role compared to the classical pathway in initiating complement activation in biofilm bacteria. Analyses of theM. tuberculosisbiofilm cell wall carbohydrate fractions revealed that there was reduced α-glucan compared to planktonically-grown bacteria. Reduced C3b/iC3b deposition directly onto biofilm carbohydrates was observed which was consistent with both the observed reduction of C3b/iC3b deposition on biofilm bacilli and a reduction in the contribution of the lectin pathway in initiating complement activation on whole bacteria from biofilms, compared to planktonically-grown bacteria.
PRSS2 stimulates tumor growth by remodeling the TME via repression of Tsp1
Authors: Sui Lufei , Wang Suming , Ganguly Debolina , El Rayes Tina , Askeland Cecilie , Børretzen Astrid , Sim Danielle , Halvorsen Ole Johan , Knutsvik Gøril , Aziz Sura , Haukaas Svein , Foulkes William D , Bielenberg Diane R. , Ziemys Arturas , Mittal Vivek , Brekken Rolf A. , Akslen Lars A. , Watnick Randolph S.
Published: March 2021

In the earliest stages of tumor development, epithelial tumors (carcinomas) are physically confined to the area of the tissue in which they form. These nascent lesions (carcinomas in situ) are sequestered from the tissue parenchyma by the basement membrane. Within the tissue parenchyma lie a myriad of cell types comprised of fibroblasts, immune and inflammatory cells and endothelial cells. Upon invasion across the basement membrane and into the tissue parenchyma, tumors must manipulate the expression of pro- and anti-tumorigenic proteins such that pro-tumorigenic factors are produced in excess to anti-tumorigenic proteins. One such anti-tumorigenic protein is Thrombospondin-1 (Tsp-1). We have previously demonstrated that stimulation of Tsp-1 in the tumor microenvironment (TME) potently inhibits tumor growth and progression and in some cases induces tumor regression. Here, we identify a novel tumor-mediated mechanism to repress the expression of Tsp-1 in the TME via secretion of the serine protease PRSS2. We demonstrate that PRSS2 represses Tsp-1, not via its enzymatic activity, but by binding to low-density lipoprotein receptor-related protein 1 (LRP1). These findings describe a novel activity for PRSS2 through binding to LRP1 and represent a potential therapeutic strategy to treat cancer by blocking the PRSS2-mediated repression of Tsp-1.
Capturing and analyzing pattern diversity: an example using the melanistic spotted patterns of leopard geckos
Authors: Glimm Tilmann , Kiskowski Maria , Moreno Nickolas , Chiari Ylenia
Published: March 2021

Animal color patterns are widely studied in ecology, evolution, and through mathematical modeling. Patterns may vary among distinct body parts such as the head, trunk or tail. As large amounts of photographic data is becoming more easily available, there is a growing need for general quantitative methods for capturing and analyzing the full complexity and details of pattern variation. Detailed information on variation in color pattern elements is necessary to understand how patterns are produced and established during development, and which evolutionary forces may constrain such a variation. Here, we develop an approach to capture and analyze variation in melanistic color pattern elements in leopard geckos. We use this data to study the variation among different body parts of leopard geckos and to draw inferences about their development. We compare patterns using 14 different indices such as the ratio of melanistic versus total area, the ellipticity of spots, and the size of spots and use these to define a composite distance between two patterns. Pattern presence/absence among the different body parts indicates a clear pathway of pattern establishment from the head to the back legs. Together with weak within-individual correlation between leg patterns and main body patterns, this suggests that pattern establishment in the head and tail may be independent from the rest of the body. We found that patterns vary greatest in size and density of the spots among body parts and individuals, but little in their average shapes. We also found a correlation between the melanistic patterns of the two front legs, as well as the two back legs, and also between the head, tail and trunk, especially for the density and size of the spots, but not their shape or inter-spot distance. Our data collection and analysis approach can be applied to other organisms to study variation in color patterns between body parts and to address questions on pattern formation and establishment in animals.
Anterior claustrum cells are responsive during behavior but not passive sensory stimulation
Authors: Ollerenshaw Douglas R , Davis Julianne , McBride Ethan G , Shelton Andrew , Koch Christof , Olsen Shawn R
Published: March 2021

The claustrum is uniquely positioned to communicate with almost all higher-order cortical areas through widespread and reciprocal anatomical projections, yet thein vivofunctional properties of claustrum neurons are not well understood. Here we use microendoscope imaging in mice to measure activity in populations of genetically-labelled Gnb4+ claustrum neurons. We find that only a small fraction of cells in the anterior claustrum are responsive to visual or auditory stimuli when delivered under passive yet wakeful conditions. In contrast, during a visual behavioral task, the majority of cells in the anterior claustrum are strongly modulated, with separate and spatially intermingled cell populations showing either increases or decreases in activity relative to spontaneous levels. Our results suggest that the Gnb4+ cells in the anterior claustrum do not represent passively presented sensory stimuli; rather, these cells are strongly engaged during behavior associated with sensory-motor transformations.
Condensin DC loads and spreads from recruitment sites to create loop-anchored TADs inC. elegans
Authors: Kim Jun , Jimenez David Sebastian , Ragipani Bhavana , Zhang Bo , Street Lena Annika , Kramer Maxwell , Albritton Sarah E , Winterkorn Lara , Morao Ana , Ercan Sevinç
Published: March 2021

Condensins are molecular motors that compact DNA via linear translocation. InC. elegans, the X-chromosome harbors a specialized condensin that participates in dosage compensation (DC). Condensin DC is recruited to and spreads from a small number ofrecruitelements on theX-chromosome (rex) and is required for the formation of topologically associating domains (TADs). We take advantage of autosomes that are largely devoid of condensin DC and TADs to address howrexsites and condensin DC give rise to the formation of TADs. When an autosome and X-chromosome are physically fused, despite the spreading of condensin DC into the autosome, no TAD was created. Insertion of a strongrexon the X-chromosome results in the TAD boundary formation regardless of sequence orientation. When the samerexis inserted on an autosome, despite condensin DC recruitment, there was no spreading or features of a TAD. On the other hand, when a“super rex”composed of sixrexsites or three separaterexsites are inserted on an autosome, recruitment and spreading of condensin DC led to formation of TADs. Therefore, recruitment to and spreading fromrexsites are necessary and sufficient for recapitulating loop-anchored TADs observed on the X-chromosome. Together our data suggest a model in whichrexsites are both loading sites and bidirectional barriers for condensin DC, a one-sided loop-extruder with movable inactive anchor.
miRador: a fast and precise tool for the prediction of plant miRNAs
Authors: Hammond Reza K. , Gupta Pallavi , Patel Parth , Meyers Blake C.
Published: March 2021

Plant microRNAs (miRNAs) are short, non-coding RNA molecules that restrict gene expression via post-transcriptional regulation and function in several essential pathways including development, growth, and stress responses. Accurately identifying miRNAs in populations of small RNA (sRNA) sequencing libraries is a computationally intensive process which has resulted in the misidentification of inaccurately annotated miRNA sequences. In recent years, criteria for miRNA annotation have been refined to reduce these misannotations. Here, we describemiRador, a novel miRNA identification tool that utilizes the most up-to-date, community-established criteria for accurate identification of miRNAs in plants. We combine target prediction and Parallel Analysis of RNA Ends (PARE) data to assess the precision of the miRNAs identified bymiRador. We comparemiRadorto other commonly used miRNA prediction tools and we find thatmiRadoris at least as precise as other prediction tools while being significantly faster than other tools.
Turning plants from passive to active material: FERONIA and microtubules independently contribute to mechanical feedback
Authors: Malivert Alice , Erguvan Özer , Chevallier Antoine , Dehem Antoine , Friaud Rodrigue , Liu Mengying , Martin Marjolaine , Peyraud Théophile , Hamant Olivier , Verger Stéphane
Published: March 2021

To survive, cells must constantly resist mechanical stress. In plants, this involves the reinforcement of cell walls, notably through microtubule-dependent cellulose deposition, and thus wall sensing. Several receptor-like kinases have been proposed to act as mechanosensors. Here we tested whether the microtubule response to stress acts downstream of known wall sensors. Using a multi-step screen with eleven mutant lines, we identify FERONIA as the primary candidate for controlling the microtubule response to stress. However, when performing mechanical perturbations, we show that the microtubule response to stress can be independent from FER. We reveal that theferoniaphenotype can be partially rescued by reducing tensile stress levels. Conversely, in the absence of both microtubules and FER, cells swell and burst like soap bubbles. Altogether, this shows that the microtubule response to stress acts as an independent pathway to resist stress, in parallel to FER. We propose that both pathways are key components to turn plant cells from passive to active material.
Online teaching benefits and challenges during pandemic COVID-19: a comparative study of Pakistan and Indonesia
Authors: Thaheem Sahib Khatoon , Zainol Abidin Mohamad Jafre , Mirza Quratulain , Pathan Habib Ullah
Published: March 2021

Purpose

The shift from physical class to online classes in the pandemic COVID-19 situation has posited opportunities as well as challenges for teachers and students. The primary purpose of this research is to investigate challenges faced and benefits availed by the teachers at the tertiary level in universities of Pakistan and Indonesia.

Design/methodology/approach

To achieve the purpose a mixed-method approach is employed to answer the three research questions of the present study. The quantitative data is obtained from the responses of 66 teachers, teaching online in Mehran UET Pakistan and 102 teachers from Indonesian university. The personal, technological, and pedagogical challenges were analyzed by descriptive statistics on SPSS. Thus, the independent-samples t-test was run to test for statistically significant differences faced by teachers in both countries.

Findings

The findings revealed that there were no statistically significant differences found in personal, and pedagogical challenges faced by both countries' teachers, whereas there is a significant difference in facing technological challenges between Pakistani and Indonesian teachers. The benefits of online teaching were investigated qualitatively by conducting semi-structured interviews with 10 teachers 5 from each country. There are very positive aspects of online teaching revealed in the interviews.

Research limitations/implications

The paper includes implications for the development of Computer Assisted Language Learning, the development of technology integrated courses, and for managing the balance between physical and online classes.

Practical implications

The findings of the study have implications on finding out the solutions of the derived challenges, further it suggests to concentrate on students of public and private universities in Pakistan and Indonesia so that a comparison of challenges faced by teachers and faced by students can be researched and evaluated and it can generate significantly different results.

Social implications

The implications on the research society and the teachers and designers' communities are very clear in this research because it paves the way forward towards the blending of technology in any way either synchronously/ asynchronously into education, further researches can be done on designing the new concepts, courses, instructional platforms for students and investigate the new dimensions and effects of them.

Originality/value

Findings have value, because two countries' context (developing countries) with respect to the comparison of the challenges and benefits is better understood, it would have different results if had done in the developed countries.