bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic score omics regression and multi-trait meta-analysis detect widespread cis-regulatory effects shaping bovine complex traits
Authors: Xiang Ruidong , Fang Lingzhao , Liu Shuli , Liu George E. , Tenesa Albert , Gao Yahui ,   CattleGTEx Consortium, Mason Brett A , Chamberlain Amanda J. , Goddard Michael E.
Published: July 2022

To complete the genome-to-phenome map, transcriptome-wide association studies (TWAS) are performed to correlate genetically predicted gene expression with observed phenotypic measurements. However, the relatively small training population assayed with gene expression could limit the accuracy of TWAS. We propose Genetic Score Omics Regression (GSOR) correlating observed gene expression with genetically predicted phenotype, i.e., genetic score. The score, calculated using variants near genes with assayed expression, provides a powerful association test between cis-effects on gene expression and the trait. In simulated and real data, GSOR outperforms TWAS in detecting causal/informative genes. Applying GSOR to transcriptomes of 16 tissue (N∼5000) and 37 traits in ∼120,000 cattle, multi-trait meta-analyses of omics-associations (MTAO) found that, on average, each significant gene expression and splicing mediates cis-genetic effects on 8∼10 traits. Supported by Mendelian Randomisation, MTAO prioritised genes/splicing show increased evolutionary constraints. Many newly discovered genes/splicing regions underlie previously thought single-gene loci to influence multiple traits.
Molecular characterization of the intact muscle spindle using a multi-omics approach
Authors: Bornstein Bavat , Heinemann-Yerushalmi Lia , Krief Sharon , Adler Ruth , Dassa Bareket , Leshkowitz Dena , Kim Minchul , Bewick Guy , Banks Robert W. , Zelzer Elazar
Published: July 2022

The proprioceptive system is essential for the control of coordinated movement, posture and skeletal integrity. The sense of proprioception is produced in the brain using peripheral sensory input from receptors such as the muscle spindle, which detects changes in the length of skeletal muscles. Despite its importance, the molecular composition of the muscle spindle is largely unknown. In this study, we generated comprehensive transcriptomic and proteomic datasets of the entire muscle spindle. We then associated differentially expressed genes with the various tissues composing the spindle using bioinformatic analysis. Immunostaining verified these predictions, thus establishing new markers for the different spindle tissues. Utilizing these markers, we identified the differentiation stages the spindle capsule cells undergo during development. Together, these findings provide comprehensive molecular characterization of the intact spindle as well as new tools to study its development and function in health and disease.
Principal and Independent Genomic Components of Brain Structure and Function
Authors: Oblong Lennart M. , Soheili-Nezhad Sourena , Trevisan Nicolò , Shi Yingjie , Beckmann Christian F. , Sprooten Emma
Published: July 2022

Introduction

The highly polygenic and pleiotropic nature of behavioural traits, psychiatric disorders, and structural and functional brain phenotypes complicate mechanistic interpretation of related genome-wide association study (GWAS) signals, such that the underlying causal biological processes remain obscure. We propose the novel method of genomic principal and independent component analysis (PCA, ICA) to decompose a large set of univariate GWAS statistics of multimodal brain traits into more interpretable latent genomic components. Here we introduce this new method and evaluate its various analytic parameters and reproducibility across independent samples.

Methods

Two releases of GWAS summary statistics from the UK biobank (UKB), with 11,086 and 22,138 participants respectively, were retrieved from the Oxford BIG-40 server. GWAS summary statistics were clumped resulting in n=165,364 single nucleotide polymorphisms (SNP) and m=2,240 imaging derived phenotypes (IDPs). Both genome-wide beta-values and their corresponding, standard-error scaled z-values were decomposed using multivariate exploratory linear optimised decomposition into independent components (MELODIC). We evaluated variance explained at multiple dimensions up to 200. We tested the reproducibility of output of dimensions 5, 10, 25, and 50 by computing Pearson’s correlation between component loadings, and Fisher Exact tests on overlap of the top SNP loadings across samples. Reproducibility statistics of the original raw and z-transformed univariate GWAS served as benchmarks. We also inspected the clustering of genomic components across neuroimaging modalities using t-SNE.

Results

The first five PCs derived from z-transformed GWAS captured 31.9% of the variance across SNP effect sizes, while 200 PCs increased the variance explained to 79.6%. Reproducibility of 10-dimensional PCs and ICs showed the best balance between model complexity and robustness, and variance explained (PCs: |rz-max|=0.33, |rraw-max|=0.30; ICs: |rz-max|=0.23, |rraw-max|=0.19), with decreasing model stability and reproducibility at higher dimensions. Both genomic PC and IC reproducibilities improved substantially relative to mean univariate GWAS reproducibility up to a dimension of 10. Genomic components clustered along neuroimaging modalities.

Conclusion

Our results indicate that these novel methods of genomic ICA and PCA decompose genetic effects on IDPs from raw GWAS statistics with high reproducibility by taking advantage of the inherent pleiotropic patterns. These findings encourage further applications of genomic ICA and PCA as fully data-driven methods to effectively reduce the dimensionality, enhance the signal to noise ratio, and improve interpretability of high-dimensional multi-trait genome-wide analyses.
Audiovisual Integration in the Human Brain: A Coordinate-based Meta-analysis
Authors: Gao Chuanji , Green Jessica J. , Yang Xuan , Oh Sewon , Kim Jongwan , Shinkareva Svetlana V.
Published: July 2022

People can seamlessly integrate a vast array of information from what we see and hear in the noisy and uncertain world. However, the neural underpinnings of audiovisual integration continue to be the topic of debate. Using strict inclusion criteria, we performed activation likelihood estimation meta-analysis on 121 neuroimaging experiments with a total of 2,092 participants. We found that audiovisual integration is linked with the coexistence of multiple integration sites including early cortical, subcortical, and higher association areas. Although activity was consistently found within the superior temporal cortex, different portions of this cortical region were identified depending on the analytical contrast used, complexity of the stimuli, and modality within which attention was directed. The context-dependent neural activity related to audiovisual integration suggests a flexible rather than fixed neural pathway for audiovisual integration. Together, our findings highlight a flexible multiple pathways model for audiovisual integration, with superior temporal cortex as the central node in these neural assemblies.
Mental health of pregnant women during the SARS-CoV-2 pandemic in France: evolution of self-perceived psychological state during the first lockdown, and anxiety frequency two months after the lockdown ended
Authors: Doncarli Alexandra , Araujo-Chaveron Lucia , Crenn-Hebert Catherine , Vacheron Marie-Noëlle , Léon Christophe , Khireddine Imane , Chin Francis , Benachi Alexandra , Tebeka Sarah , Regnault Nolwenn
Published: July 2022

Previous pandemics and related lockdowns have had a deleterious impact on pregnant women’s mental health. We studied the impact of the SARS-CoV-2/Covid-19 pandemic and France’s first lockdown on pregnant women’s mental health.

A cross-sectional study was conducted in July 2020 using a web-questionnaire completed by 500 adult women who were pregnant during the first lockdown in France (March-May 2020). Questions focused on their self-perceived psychological state and affects they felt before and during the lockdown and anxiety symptomatology (HAD) two months after it ended. A robust variance Poisson regression model was used to estimate adjusted prevalence ratios (aPR) for anxiety and self-perceived psychological state evolution.

One in five respondents (21.1%) reported psychological deterioration during lockdown. Associated determinants were: i) little or no social support (self-perceived) (aRP=1.77, 95%CI[1.18-2.66]), ii) increased workload (1.65, [1.02-2.66]), and iii) poor/moderate knowledge about SARS-CoV-2 transmission (1.60, [1.09-2.35]). Seven percent of women reporting psychological deterioration had access to professional psychological support during lockdown, while 19% did not despite wanting it. Women reported heightened powerlessness (60.3%), frustration (64%) and fear (59.2%) during lockdown.

One in seven respondents (14.2%, 95%CI[10.9-18.2]) had anxiety symptoms. Determinants associated: i) at least one pregnancy-related pathology (aPR=1.82, 95%CI[1.15-2.88]), ii) overweightness or obesity (1.61, [1.07-2.43]), iii) one child under the age of six years in the household during the lockdown (3.26, [1.24-8.53]), iv) little or no social support (self-perceived) during the lockdown (1.66, [1.07-2.58]), v) friend or relatives diagnosed with Covid-19 or with symptoms of the disease (1.66; [1.06-2.60]), vi) no access to medication for psychological distress (2.86, [1.74-4.71]), and vii) unsuccessfully seeking exchanges with healthcare professionals about their pregnancy during the pandemic (1.66, [1.08-2.55]).

Our results can guide prevention and support policies for pregnant women during pandemics, current or future, with or without lockdowns. Preventing perinatal mental health problems is essential to ensure a supportive environment for the child’s development.
Variation in maternal mortality in Sidama Regional State, southern Ethiopia: A population based cross sectional household survey
Authors: Kea Aschenaki Zerihun , Lindtjorn Bernt , Gebretsadik Achamyelesh , Hinderaker Sven Gudmund
Published: July 2022

Introduction

Maternal mortality studies conducted at national level do not provide information needed for planning and monitoring health programs at lower administrative levels. The aim of this study was to measure maternal mortality, identify risk factors and district level variations in Sidama Regional State, southern Ethiopia.

Methods

A cross sectional population-based survey was carried in households where a woman reported pregnancy and birth outcomes in the past five year. The study was conducted in the Sidama Regional State, southern Ethiopia, from July 2019 to May 2020. Multi-stage cluster sampling technique was employed. The outcome variable of the study was maternal mortality. Complex sample logistic regression analysis was applied to assess variables independently associated with maternal mortality.

Results

We registered 10602 live births (LB) and 48 maternal deaths yielding the overall maternal mortality ratio (MMR) of 419; 95% CI: 260-577 per 100,000 LB. Aroresa districts had the highest MMR with 1142 (95% CI: 693-1591) per 100,000 LB. Leading causes of death were haemorrhage 21 (41%) and eclampsia 10 (27%). Thirty (59%) mothers died during labour or with 24 hours after delivery, 25 (47%) died at home and 17 (38%) at health facility. Mothers who did not have formal education had higher risk of maternal death (AOR: 4.3; 95% CI: 2.0 – 9.2). The risk of maternal death was higher in districts with low midwife to population ratio (AOR: 3.0; 95% CI: 1.2-7.9).

Conclusion

The high maternal mortality with district level variations in Sidama region highlights the importance of improving obstetric care and employing targeted interventions in areas with high mortality rates. Due attention should be given to improving access to female education. Additional midwives has to be trained and deployed to improve maternal health services and consequently save the life of mothers.
mergem: merging and comparing genome-scale metabolic models using universal identifiers
Authors: Hari Archana , Lobo Daniel
Published: July 2022

Numerous methods exist to produce and refine genome-scale metabolic models. However, due to the use of incompatible identifier systems for metabolites and reactions, computing and visualizing the metabolic differences and similarities of such models is a current challenge. Furthermore, there is a lack of automated tools that can combine the strengths of multiple reconstruction pipelines into a curated single comprehensive model by merging different drafts, which possibly use incompatible namespaces. Here we presentmergem, a novel method to compare and merge two or more metabolic models. Using a universal metabolic identifier mapping system constructed from multiple metabolic databases,mergemrobustly can compare models from different pipelines and merge their common elements.mergemis implemented as a command line tool, a Python package, and on the web-application Fluxer, which allows simulating and visually comparing multiple models with different interactive flux graphs. The ability to merge and compare diverse genome scale metabolic models can facilitate the curation of comprehensive reconstructions and the discovery of unique and common metabolic features among different organisms.
Vitamin C is an efficient natural product for prevention of SARS-CoV-2 infection by targeting ACE2 in both cell and in vivo mouse models
Authors: Zuo Yibo , Zheng Zhijin , Huang Yingkang , He Jiuyi , Zang Lichao , Ren Tengfei , Cao Xinhua , Miao Ying , Yuan Yukang , Liu Yanli , Ma Feng , Tian Sheng , Dai Jianfeng , Ding Qiang , Zheng Hui
Published: July 2022

ACE2 is a major receptor for cell entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2’s binding, how to efficiently and flexibly control ACE2 levels for prevention of SARS-CoV-2 infection has not been explored. Here, we revealed Vitamin C (VitC) administration as an effective strategy to prevent SARS-CoV-2 infection. VitC reduced ACE2 protein levels in a dose-dependent manner, while partial reduction of ACE2 can greatly restrict SARS-CoV-2 infection. Further studies uncovered that USP50 is a crucial regulator of ACE2 protein levels, and VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination at Lys788 and degradation of ACE2, without disrupting ACE2 transcriptional expression. Importantly, VitC administration reduced host ACE2 and largely blocked SARS-CoV-2 infection in mice. This study identified anin vivoACE2 balance controlled by both USP50 and an essential nutrient VitC, and revealed a critical role and application of VitC in daily protection from SARS-CoV-2 infection.

Highlights

VitC reduces ACE2 protein levels in a dose-dependent manner

VitC and USP50 regulate K48-linked ubiquitination at Lys788 of ACE2

VitC blocks the interaction between USP50 and ACE2

VitC administration lowers host ACE2 and prevents SARS-CoV-2 infectionin vivo

Abstract Figure

The deubiquitinase USP50 controls ACE2 protein stability and levels, while Vitamin C blocks the USP50-ACE2 interaction and therefore results in ACE2 degradation, offering a flexible and efficient approach to protection of the host from SARS-CoV-2 infection.
The SPARC complex defines RNAPII promoters in Trypanosoma brucei
Authors: Staneva Desislava P. , Bresson Stefan , Auchynnikava Tatsiana , Spanos Christos , Rappsilber Juri , Jeyaprakash A. Arockia , Tollervey David , Matthews Keith R. , Allshire Robin C.
Published: July 2022

Kinetoplastids are a highly divergent lineage of eukaryotes with unusual mechanisms for regulating gene expression. We previously surveyed 65 putative chromatin factors in the kinetoplastid Trypanosoma brucei. Our analyses revealed that the predicted histone methyltransferase SET27 and the Chromodomain protein CRD1 are tightly concentrated at RNAPII transcription start regions (TSRs). Here we report that SET27 and CRD1, together with four previously uncharacterized constituents, form the SET27 promoter-associated regulatory complex (SPARC), which is specifically enriched at TSRs. SET27 loss leads to aberrant RNAPII recruitment to promoter sites, accumulation of polyadenylated transcripts upstream of normal transcription start sites, and conversion of some normally unidirectional promoters to bidirectional promoters. Transcriptome analysis in the absence of SET27 revealed upregulated mRNA expression in the vicinity of SPARC peaks within the main body of chromosomes in addition to derepression of genes encoding variant surface glycoproteins (VSGs) located in subtelomeric regions. These analyses uncover a novel chromatin-associated complex required to establish accurate promoter position and directionality.
Fate Bias and Transcriptional Memory of human B cells
Authors: Swift Michael , Horns Felix , Quake Stephen R.
Published: July 2022

Lineage tracking offers a direct approach to study cell fate determination. In this work we combined single cell transcriptomics and lineage tracing to better understand fate-choice in human B cells. Using the antibody sequence to trace cell lineage during in vitro differentiation, we identified intrinsic proliferative and cell fate biases of B cell subtypes. Clonal analysis revealed that IgM memory B cells were more proliferative than any other B cell subtype, and that cells from the same clone had highly concordant fates. We found that transcriptional memory within clones varies across genes, with strongest persistence in genes related to cell fate determination. Similar persistent transcriptional programs were observed in human plasma cells from bone marrow, suggesting that these programs maintain long-term cell fate in vivo. These results show that cell-intrinsic fate bias influences human B cell differentiation and reveal molecular programs underpinning cell fate determination in B cells.
A zebrafish model of COVID-19-associated cytokine storm syndrome reveals that the Spike protein signals via TLR2
Authors: Tyrkalska Sylwia D. , Martínez-López Alicia , Pedoto Annamaria , Candel Sergio , Cayuela María L. , Mulero Victoriano
Published: July 2022

Understanding the mechanism of virulence of SARS-CoV-2 and host innate immune responses are essential to develop novel therapies. One of the most studied defense mechanisms against invading pathogens, including viruses, are Toll-like receptors (TLRs). Among them, TLR3, TLR7, TLR8 and TLR9 detect different forms of viral nucleic acids in endosomal compartments, whereas TLR2 and TLR4 recognize viral structural and nonstructural proteins outside the cell. Although many different TLRs have been shown to be involved in SARS-CoV-2 infection and detection of different structural proteins, most studies have been performed in vitro and the results obtained are rather contradictory. In this study, we report using the unique advantages of the zebrafish model for in vivo imaging and gene editing that the S1 domain of the Spike protein from the Wuhan strain (S1WT) induced hyperinflammation in zebrafish larvae via a Tlr2/Myd88 signaling pathway and independently of interleukin-1β production. In addition, S1WT also triggered emergency myelopoiesis, but in this case through a Tlr2/Myd88-independent signaling pathway. These results shed light on the mechanisms involved in the COVID-19-associated cytokine storm syndrome.
Degraded RNA from human anterior cruciate ligaments yields valid gene expression profiles
Authors: Strawn Matthew D. , Fisher Geoffrey D. , Perry Cody J. , Hashemi Javad , Mansouri Hossein , Ferguson Matthew P. , Zumwalt Mimi , Brindley George W. , Slauterbeck James R. , Hardy Daniel M.
Published: July 2022

Background

Correlating gene expression patterns with biomechanical properties of connective tissues provides insight into molecular processes underlying development and maintenance of the tissues’ physical characteristics. Cadaveric tissues such as human knees are widely considered suitable for biomechanical studies, but their usefulness for gene expression experiments is potentially limited by unavoidable, nuclease-mediated degradation of RNA.

Methods

We quantified mRNAs encoding 84 extracellular matrix components and five housekeeping proteins in intact and partially degraded RNA from human anterior cruciate ligaments (ACLs), and compared relative amounts of the individual mRNAs by regression analysis.

Results

Human ACL RNA degraded in vitro by limited ribonuclease digestion (N=6) resembled degraded RNA isolated from cadaveric tissue. PCR threshold cycle (Ct) values from degraded RNAs ranged variably higher than values obtained from their corresponding non-degraded RNAs, reflecting both the expected loss of target templates in the degraded preparations as well as differences in the extent of degradation. Relative Ct values obtained for mRNA targets in degraded preparations correlated strongly with the corresponding target levels in non-degraded RNA, both for each ACL as well as for pooled results from all six ACLs. Nuclease-mediated degradation produced similar, strongly correlated losses of housekeeping and non-housekeeping gene mRNAs. Expression profiling of RNA degraded in situ yielded comparable results, confirming that in vitro digestion suitably mimicked degradation by endogenous ribonucleases in frozen and thawed ACL.

Conclusion

PCR-based expression analyses can yield valid mRNA profiles from partially degraded RNA preparations such as those obtained from cadaveric knees and other skeletal motion segments used in biomechanical studies. Legitimate comparisons between variably degraded tissues can be made by normalizing quantitative data to an appropriate housekeeping transcript.
Population Structure and Ecology of the African elephant (Loxodonta africana, Blumenbach, 1797) in Chebera Churchura National Park, Ethiopia
Authors: Tsegaye Adane , Bekele Afework , Atikem Anagaw
Published: July 2022

An investigation on population structure and ecology of the African elephants (Loxodonta africana) was carried out in Chebera Churchura National Park, Ethiopia during the wet and dry seasons of 2020 –2021. Sample counts using distance sampling of the African elephants were carried out in an area of 1, 410 km2. The total population estimated was 756 individuals, and the mean population density estimated was 0.53/km2. Among these, females constituted 52.12% and males 36.07%. The remaining 11.8% of the population was young of both sexes. It was difficult to categorize the young into male and female in the field, as their primary sexual characteristics were not easily visible.

Male to female sex ratio was 1.00:-1.42. Age structure was dominated by adults, which constituted 53.83% of the total population. Sub-adults comprised 19.11%, juveniles contributed 15.18% and calves accounted for 12.11% of the population. The herd size ranged from 1 to 149 individuals and the mean herd size during wet and dry seasons were 16.5 and 50.25, respectively. The African elephants were distributed in four habitat types: grassland, woodland, montane forest and riverine habitats in the study area. They were observed more in the riverine vegetation types during the dry season. Relative abundance of food resources, green vegetation cover and water availability in the area were the major factors governing their distribution in the present study area.
A PAK kinase family member and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration
Authors: Doddihal Viraj , Mann Frederick G. , Ross Eric , McKinney Sean A. , Alvarado Alejandro Sánchez
Published: July 2022

Successful regeneration of missing tissues requires seamless integration of positional information along the body axes. Planarians, which regenerate from almost any injury, use conserved, developmentally important signaling pathways to pattern the body axes. However, the molecular mechanisms which facilitate crosstalk between these signaling pathways to integrate positional information remain poorly understood. Here, we report a p21-activated kinase (smed-pak1) which functionally integrates the anterior-posterior (AP) and the medio-lateral (ML) axes. pak1 inhibits WNT/β-catenin signaling along the AP axis and, functions synergistically with the β-catenin-independent WNT signaling of the ML axis. Furthermore, this functional integration is dependent on warts and merlin - the components of the Hippo/Yorkie (YKI) pathway. Hippo/YKI pathway is a critical regulator of body size in flies and mice, but our data suggest the pathway is required to pattern body axes in planarians. Our study provides a signaling network integrating positional information which can mediate coordinated growth and patterning during planarian regeneration.
Local fat content determines global and local stiffness in livers with simple steatosis
Authors: Li David , Janmey Paul A. , Wells Rebecca G.
Published: July 2022

Fat accumulation during liver steatosis precedes inflammation and fibrosis in fatty liver diseases, and is associated with disease progression. Despite a large body of evidence that liver mechanics play a major role in liver disease progression, the effect of fat accumulation by itself on liver mechanics remains unclear. Thus, we conducted ex vivo studies of liver mechanics in rodent models of simple steatosis to isolate and examine the mechanical effects of intrahepatic fat accumulation, and found that fat accumulation softens the liver. Using a novel adaptation of microindentation to permit association of local mechanics with microarchitectural features, we found evidence that the softening of fatty liver results from local softening of fatty regions rather than uniform softening of the liver. These results suggest that fat accumulation itself exerts a softening effect on liver tissue. This, along with the localized heterogeneity of softening within the liver, has implications in what mechanical mechanisms are involved in the progression of liver steatosis to more severe pathologies and disease. Finally, the ability to examine and associate local mechanics with microarchitectural features is potentially applicable to the study of the role of heterogeneous mechanical microenvironments in both other liver pathologies and other organ systems.
Heterogeneity of Tethered Agonist Signaling in Adhesion G Protein-Coupled Receptors
Authors: Dates Andrew N. , Jones Daniel T.D. , Smith Jeffrey S. , Skiba Meredith A. , Rich Maria F. , Burruss Maggie M. , Kruse Andrew C. , Blacklow Stephen C.
Published: July 2022

Adhesion G Protein-Coupled Receptor (aGPCR) signaling influences development and homeostasis in a wide range of tissues. In the current model for aGPCR signaling, ligand binding liberates or unmasks a highly conserved tethered agonist (TA) that acts as an intramolecular ligand to stimulate G protein coupling. However, a systematic, comprehensive examination of signaling has not been performed for all aGPCR family members. Here, we report a platform for profiling TA-dependent activities of aGPCRs in several different assays and apply it to all 33 human family members. Activity profiling identified a heterogeneity of responses among these aGPCRs, with only ∼50% showing robust, TA-dependent signals. AlphaFold2 predictions assessing TA engagement in the predicted intramolecular binding pocket aligned with the TA-dependence of the cellular responses. The signaling information in this dataset is a comprehensive resource relevant for the investigation of all human aGPCRs and for targeting aGPCRs therapeutically.
Low-cost platform for multi-animal chronic local field potential video monitoring with graphical user interface (GUI) for seizure detection and behavioral scoring
Authors: Tarcsay Gergely , Boublil Brittney Lee , Ewell Laura A.
Published: July 2022

Experiments employing chronic monitoring of neurophysiological signals and video are commonly used in studies of epilepsy to characterize behavioral correlates of seizures. Our objective was to design a low-cost platform that enables chronic monitoring of several animals simultaneously, synchronizes bilateral local field potential and video streams in real-time, and parses recorded data into manageable file sizes. We present a hardware solution leveraging Intan and Open Ephys acquisition systems and a software solution implemented in Bonsai. The platform was tested in 48-hour continuous recordings simultaneously from multiple mice (male and female) with chronic epilepsy. To enable seizure detection and scoring, we developed a graphical user interface (GUI) that reads the data produced by our workflow and allows a user with no coding expertise to analyze events. Our Bonsai workflow was designed to maximize flexibility for a wide variety of experimental applications, and our use of the Open Ephys acquisition board would allow for scaling recordings up to 128 channels per animal.

SIGNIFICANCE STATEMENT

We present a low-cost hardware and software solution intended for multi-animal chronic seizure monitoring, that prioritizes experimental freedom, and requires no coding expertise of the user. We provide details for using an Intan adapter board to enable user freedom regarding the type of electrodes used. Video and local field potential data streams are synchronized and parsed in Bonsai – an open-source visual programming language that has pre-written libraries that allow our workflow to be adapted to other data types or to integrate with open-source toolboxes. Finally, for those intending to use our platform for seizure monitoring, we provide an accessible GUI to aid in seizure detection and behavioral scoring.
Functional characterization of multidomain protein Vip3Aa from Bacillus thuringiensis reveals a strategy to increase its insecticidal potency
Authors: Jiang Kun , Chen Zhe , Shi Yiting , Jiao Xuyao , Cai Jun , Gao Xiang
Published: July 2022

Microbially derived, protein-based biopesticides offer a more sustainable pest management alternative to synthetic pesticides. Vegetative insecticidal proteins (Vip3), multidomain proteins secreted by Bacillus thuringiensis, represent a second-generation insecticidal toxin that have been used in transgenic crops. However, the molecular mechanism underlying Vip3’s toxicity is poorly understood. Here, we determine the distinct functions and contributions of the domains of the Vip3Aa protein to its toxicity against Spodoptera frugiperda larvae. Vip3Aa domains II and III (DII-DIII) bind the midgut epithelium, while DI maintains the tetrameric state of the Vip3Aa protoxin, which is essential for its stability and toxicity. DI-DIII can be activated by midgut proteases, and exhibits ex vivo cytotoxicity similar to full-length Vip3Aa. We also determine that DV binds the peritrophic matrix via its glycan-binding activity, which is essential for Vip3Aa insecticidal activity. We further show that Vip3Aa has multiple protease activation sites and that introducing additional cleavage sites between DI and DII can increase the proteolysis efficiency and boost Vip3Aa insecticidal potency. This study provides insights into Vip3Aa’s mode-of-action and demonstrates a proof-of-concept strategy to enhance the insecticidal potency of Vip3Aa, which should significantly improve its application and development as a biopesticide.
Pangenome analysis of SARS-CoV2 strains to Identify Potential vaccine targets by Reverse Vaccinology
Authors: Haseeb Muhammad , Amir Afreenish , Irshad Hamza
Published: July 2022

Background

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) leads to respiratory failure and obstructive alveolar damage, which may be fatal in immunocompromised individuals. COVID-19 pandemic has severe global implications badly, and the situation in the world is depreciating with the emergence of novel variants. The aim of our study is to explore the genome of SARS-CoV2 followed by in silico reverse vaccinology analysis. This will help to identify the most putative vaccine candidate against the virus in a robust manner and enables cost-effective development of vaccines compared with traditional strategies.

Methods

The genomic sequencing data is retrieved from NCBI (Reference Sequence Number NC_045512.2). The sequences are explored through comparative genomics approaches by GENOMICS to find out the core genome. The comprehensive set of proteins obtained was employed in computational vaccinology approaches for the prediction of the best possible B and T cell epitopes through ABCpred and IEDB Analysis Resource, respectively. The multi-epitopes were further tested against human toll-like receptor and cloned in E. coli plasmid vector.

Findings

The designed Multiepitope Subunit Vaccine was non-allergenic, antigenic (0.6543), & non-toxic, with significant connections with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 84.38%. It has 276 amino acids, consisting of an adjuvant with the aid of EAAAK linker, AAY linkers used to join the 4 CTL epitopes, GPGPG linkers used to join the 3 HTL epitopes and KK linkers used to join the 7 B-cell epitopes. MESV docking with human pathogenic toll-like receptors-3 (TLR3) exhibited a stable & high binding affinity. An in-silico codon optimization approach was used in the codon system of E. coli (strain K12) to obtain the GC-Content of Escherichia coli (strain K12): 50.7340272413779 and CAI-Value of the improved sequence: 0.9542834278823386. The multi-epitope vaccine’s optimized gene sequence was cloned in-silico in E. coli plasmid vector pET-30a (+), BamHI and HindIII restriction sites were added to the N and C-terminals of the sequence, respectively.

Conclusion

There is a pressing need to combat COVID-19 and we need quick and reliable approaches against Covid-19. By using In-silico approaches, we acquire an effective vaccine that could trigger adequate immune responses at the cellular and humoral level. The suggested sequences can be further validated through in vivo and in vitro experimentation.

Statement of Significance

Current developments in the immunological bioinformatics areas has resulted in different servers and tools that are cost and time efficient for the traditional vaccine development. Though for designing a multiple epitope vaccine the antigenic epitopes prediction of a relevant protein by immunoinformatic methods are very helpful.
Gwaihir: Jupyter Notebook graphical user interface for Bragg coherent diffraction imaging
Authors: Simonne David , Carnis Jérôme , Atlan Clément , Chatelier Corentin , Favre-Nicolin Vincent , Dupraz Maxime , Leake Steven J. , Zatterin Edoardo , Resta Andrea , Coati Alessandro , Richard Marie-Ingrid
Published: July 2022

Bragg coherent X-ray diffraction is a nondestructive method for probing material structure in three dimensions at the nanoscale, with unprecedented resolution in displacement and strain fields. This work presents Gwaihir, a user-friendly and open-source tool to process and analyze Bragg coherent X-ray diffraction data. It integrates the functionalities of the existing packages bcdi and PyNX in the same toolbox, creating a natural workflow and promoting data reproducibility. Its graphical interface, based on Jupyter Notebook widgets, combines an interactive approach for data analysis with a powerful environment designed to link large-scale facilities and scientists.
Neutron interference from a split-crystal interferometer
Authors: Lemmel H. , Jentschel M. , Abele H. , Lafont F. , Guerard B. , Sasso C. P. , Mana G. , Massa E.
Published: July 2022

The first successful operation of a neutron interferometer with a separate beam-recombining crystal is reported. This result was achieved at the neutron interferometry setup S18 at the ILL in Grenoble by a collaboration between TU Wien, ILL, Grenoble, and INRIM, Torino. While previous interferometers have been machined out of a single-crystal block, in this work two crystals were successfully aligned on nanoradian and picometre scales, as required to obtain neutron interference. As a decisive proof-of-principle demonstration, this opens the door to a new generation of neutron interferometers and exciting applications.
Self-transformation of solid CaCO3 microspheres into core-shell and hollow hierarchical structures revealed by coherent X-ray diffraction imaging
Authors: Beuvier Thomas , Chushkin Yuriy , Zontone Federico , Gibaud Alain , Cherkas Oxana , Da Silva Julio , Snigireva Irina
Published: July 2022

The self-transformation of solid microspheres into complex core-shell and hollow architectures cannot be explained by classical Ostwald ripening alone. Here, coherent X-ray diffraction imaging and 3D X-ray fluorescence were used to visualize in 3D the formation of hollow microparticles of calcium carbonate in the presence of polystyrene sulfonate (PSS). During the dissolution of the core made from 10–25 nm crystals, the shell developed a global spheroidal shape composed of an innermost layer of 30 nm particles containing high PSS content on which oriented vaterite crystals grew with their c axis mainly oriented along the meridians. The stabilizing role of PSS and the minimization of the intercrystal dipolar energy can explain in combination with Ostwald ripening the formation of these sophisticated structures as encountered in many systems such as ZnO, TiO2, Fe2O3, Co3O4, MnO2, Cu2O, ZnS, CaCO3 and Ca8H2(PO4)6·5H2O.
Organism-specific differences in the binding of ketoprofen to serum albumin
Authors: Czub Mateusz P. , Stewart Alan J. , Shabalin Ivan G. , Minor Wladek
Published: July 2022

Serum albumin is a circulatory transport protein that has a highly conserved sequence and structure across mammalian organisms. Its ligand-binding properties are of importance as albumin regulates the pharmacokinetics of many drugs. Due to the high degree of structural conservation between mammalian albumins, nonhuman albumins such as bovine serum albumin or animal models are often used to understand human albumin–drug interactions. Ketoprofen is a popular nonsteroidal anti-inflammatory drug that is transported by albumin. Here, it is revealed that ketoprofen exhibits different binding-site preferences when interacting with human serum albumin compared with other mammalian albumins, despite the conservation of binding sites across species. The reasons for the observed differences were explored, including identifying ketoprofen binding determinants at specific sites and the influence of fatty acids and other ligands on drug binding. The presented results reveal that the drug-binding properties of albumins cannot easily be predicted based only on a complex of albumin from another organism and the conservation of drug sites between species. This work shows that understanding organism-dependent differences is essential for assessing the suitability of particular albumins for structural or biochemical studies.
Effects of trace elements Hf and Si on oxidation behavior of Co-Ni-Al-W-based superalloys at 900°C
Authors: Zhou Fanjie , Ma Chunmei , Zhang Yuheng , Wang Jialu , Fu Huadong
Published: July 2022

Purpose

This study aims to control the oxidation resistance of Co-based deformed superalloys by adding trace elements Hf and Si.

Design/methodology/approach

The effects and mechanism of trace elements Hf and Si on the oxidation behavior of Co-Ni-Al-W-based forged superalloys were investigated by cyclic oxidation at 900°C.

Findings

The results show that the addition of trace elements Hf and Si does not affect the type of surface oxides of Co-Ni-based superalloys, and the oxidation layers of the alloys are TiO2, spinel, Cr2O3, TaTiO4, Al2O3 and TiN from outside to inside. However, the addition of elements can affect the activity of Cr and Ti elements; decrease the formation of TiO2 and TaTiO4 layers, which are harmful to the oxidation performance; and then improve the oxidation resistance of the alloy.

Originality/value

The relevant research results can not only optimize the microalloying element content of Co-Ni-Al-W-based superalloys, but also provide a new perspective for the composition optimization design of superalloys.
Examining the dark side of using gamification elements in online community engagement: an application of PLS-SEM and ANN modeling
Authors: Srivastava Gautam , Bag Surajit , Rahman Muhammad Sabbir , Pretorius Jan Harm Christiaan , Gani Mohammad Osman
Published: July 2022

Purpose

The negative influence of gamification on online communities has received little attention in the available literature. The study examines the adverse effects of gamification during engaging in online communities.

Design/methodology/approach

Gap-spotting methods were used to develop the research questions, followed by model development using the social exchange and social-network theories. Data were collected from 429 samples. The study applied partial least squares structural equation modeling to test the research hypotheses followed by ANN application.

Findings

The study identified five factors related to gamification that have a significant adverse effect on the mental and emotional well-being of the users. Furthermore, the results of PLS-SEM were then compared through an artificial neural network (ANN) analytic process, revealing consistency for the model. This research presents a theoretical contribution by providing critical insights into online gamers' mental and emotional health. It implies that gamification can even bring mental and emotional disturbance. The resulting situation might lead to undesirable social consequences.

Practical implications

The result highlights the managerial and social relevance from the perspective of a developing country. As respondents are becoming more engrossed in online gaming, managers and decision-makers need to take preventive measures to overcome the dark side of online gaming.

Originality/value

The present study shows that the dark side of gamification has some adverse effects on human mental and emotional health. The study's findings can be used to improve gamification strategies while engaging online communities.
Effectiveness of peer support to reduce depression, anxiety and stress among migrant construction workers in Singapore
Authors: Palaniappan Kavitha , Rajaraman Natarajan , Ghosh Santu
Published: July 2022

Purpose

The aim of this study was to determine the effectiveness of promoting peer support to reduce depression, anxiety and stress among migrant construction workers in Singapore.

Design/methodology/approach

This longitudinal study drew participants from migrant workers of various nationalities in the construction sector in Singapore. Baseline data pertaining to depression, anxiety and stress was established using the DASS-21 questionnaire, and salient covariates such as demographic factors and work environment factors recorded using suitable questionnaires. Intervention was training of participants on peer support techniques, supplemented by episodic support by trained counsellors. At the end of 6 months, DASS-21 was again deployed to obtain the post-results. Comparison of baseline with post-results data was performed to evaluate effectiveness of the peer support intervention.

Findings

Statistically significant reduction was observed in measures of all the three parameters studied, namely, depression, anxiety and stress. A decrease of 3.3 (95% CI:2.3 to 4.3) points in mean depression score, a decrease of 2.6 (95% CI: 1.6 to 3.7) points in mean anxiety score and a decrease of 2.7 (with 95% CI: 1.6 to 4.0) points in mean stress scores on the DASS-21 scale were recorded. Conclusions: Peer support is effective in improving mental health of migrant workers in the construction sector in Singapore. This intervention should be considered among other measures to improve their welfare.

Originality/value

This is the first paper that talks about the mental health of migrant workers pre-COVID and hence would be a strong paper for the future comparative studies for pre-and post-COVID periods. This is the first paper that addresses the benefits of peer-support among migrant workers to improve their mental wellbeing.
Providing antibacterial properties to denim and non-denim trousers with encapsulation technology
Authors: İvedi İsmail , Güneşoğlu Bahadır , Karavana Sinem Yaprak , Erkan Gökhan , Kartal Gülşah Ekin , Sariisik Ayse Merih
Published: July 2022

Purpose

The aim was to prepare antibacterial microcapsules and transferred to denim and non-denim (canvas) trousers.

Design/methodology/approach

For this purpose, lavender and sweet almond oil as active agents were encapsulated with ethylcellulose shell with a spray dryer method and carried out capsule optimization studies.

Findings

The particle diameter of the capsules ranged between 0.61 and 8.76 µm, SPAN value was 1.608 and the mean particle size was 4 µm. The mass yields of capsules ranged between 35.0 and 75.4 %w/w. Denim fabrics were treated with prepared capsules by exhaustion and spraying methods. It was seen that microcapsules provided a reduction of bacteria by over 97% against both Staphylococcus aureus and Escherichia coli and the fabrics still showed an antibacterial effect after five washing cycles.

Originality/value

When application methods were compared, the spraying method was found to be more sustainable process than exhaustion and could be used as an alternative for reducing energy consumption and capsules could provide antibacterial properties to the fabrics.
Secondary school organisation and home–school collaboration: a tale of two systems
Authors: Barnard Peter A.
Published: July 2022

Purpose

This conceptual paper explores the relationship between school structure, organisation, and home–school collaboration. It argues that the traditional and dominant secondary school model based on same-age organisation acts in ways that constrain home–school collaboration while claiming to value it. The paper proposes an alternative model (vertical tutoring), one that relies on home–school collaboration and developing the capacity to absorb the complexity that collaboration creates

Design/methodology/approach

Models of home–school collaboration abstracted from the research literature are set within a framework of organisational studies, complexity science, and systemic thinking, revealing incongruities between claimed values and operational practices. The paper contrasts the frailties endemic to same-age organisation with the advantages claimed by schools that have adopted a vertical tutoring (VT) system

Findings

The choice of organisational structure is a major influence on a school's capacity to develop the home–school collaboration needed to liberate individual and organisational learning. Same-age organisational structure has a reduced capacity for building the collaborative partnerships needed to engage parents in their child's learning process. Multi-age organisation matches capacity with learning demand, enabling agency and liberating management.

Research limitations/implications

Current approaches to modelling rarely consider same-age operative structure and so are destined to restrict rather than enable home–school collaboration. The adoption of VT by schools broadens the scope of organisational analysis, positing a need for multi-disciplinary research able to link the form of school organisation to individual and organisational learning.

Originality/value

VT is rarely mentioned in the research literature as an alternative to same-age structuration. This paper addresses this issue and draws upon complexity science, autopoietic theory, and systemic thinking to explain why current models of home–school collaboration are insufficiently situated in organisational practice.