bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotyping heart failure using model-based analysis and physiology-informed machine learning
Authors: Jones Edith , Randall E. Benjamin , Hummel Scott L. , Cameron David , Beard Daniel A. , Carlson Brian E.
Published: March 2021

To determine the underlying mechanistic differences between diagnoses of Heart Failure (HF) and specifically heart failure with reduced and preserved ejection fraction (HFrEF & HFpEF), a closed loop model of the cardiovascular system coupled with patient specific transthoracic echocardiography (TTE) and right heart catheterization (RHC) measures was used to identify key parameters representing cardiovascular hemodynamics. Thirty-one patient records (10 HFrEF, 21 HFpEF) were obtained from the Cardiovascular Health Improvement Project (CHIP) database at the University of Michigan. Model simulations were tuned to match RHC and TTE pressure, volume and cardiac output measures in each patient with average error between data and model of 4.87 ± 2%. The underlying physiological model parameters were then plotted against model-based norms and compared between the HFrEF and HFpEF group. Our results confirm that the main mechanistic parameter driving HFrEF is reduced left ventricular contractility, while for HFpEF a much wider underlying phenotype is presented. Conducting principal component analysis (PCA),k-means, and hierarchical clustering on the optimized model parameters, but not on clinical measures, shows a distinct group of HFpEF patients sharing characteristics with the HFrEF cohort, a second group that is distinct as HFpEF and a group that exhibits characteristics of both. Significant differences are observed (p-value<.001) in left ventricular active contractility and left ventricular relaxation, when comparing HFpEF patients to those grouped as similar to HFrEF. These results suggest that cardiovascular system modeling of standard clinical data is able to phenotype and group HFpEF as different subdiagnoses, possibly elucidating patient-specific treatment strategies.
Large scale genomic rearrangements in selectedArabidopsis thalianaT-DNA lines are caused by T-DNA insertion mutagenesis
Authors: Pucker Boas , Kleinbölting Nils , Weisshaar Bernd
Published: March 2021

Background

Experimental proof of gene function assignments in plants is based on mutant analyses. T-DNA insertion lines provided an invaluable resource of mutants and enabled systematic reverse genetics-based investigation of the functions ofArabidopsis thalianagenes during the last decades.

Results

We sequenced the genomes of 14A. thalianaGABI-Kat T-DNA insertion lines, which eluded flanking sequence tag-based attempts to characterize their insertion loci, with Oxford Nanopore Technologies (ONT) long reads. Complex T-DNA insertions were resolved and 11 previously unknown T-DNA loci identified, resulting in about 2 T-DNA insertions per line and suggesting that this number was previously underestimated. T-DNA mutagenesis caused fusions of chromosomes along with compensating translocations to keep the gene set complete throughout meiosis. Also, an inverted duplication of 800 kbp was detected. About 10% of GABI-Kat lines might be affected by chromosomal rearrangements, some of which do not involve T-DNA. Local assembly of selected reads was shown to be a computationally effective method to resolve the structure of T-DNA insertion loci. We developed an automated workflow to support investigation of long read data from T-DNA insertion lines. All steps from DNA extraction to assembly of T-DNA loci can be completed within days.

Conclusion

Long read sequencing was demonstrated to be an effective way to resolve complex T-DNA insertions and chromosome fusions. Many T-DNA insertions comprise not just a single T-DNA, but complex arrays of multiple T-DNAs. It is becoming obvious that T-DNA insertion alleles must be characterized by exact identification of both T-DNA::genome junctions to generate clear genotype-to-phenotype relations.
Proteomic analysis identifies novel binding partners of BAP1
Authors: Baas Roy , van der Wal Fenna J. , Bleijerveld Onno B. , van Attikum Haico , Sixma Titia K.
Published: March 2021

BRCA1-associated protein 1 (BAP1) is a tumor suppressor and its loss can result in mesothelioma, uveal and cutaneous melanoma, clear cell renal cell carcinoma and bladder cancer. BAP1 is a deubiquitinating enzyme of the UCH class that has been implicated in various cellular processes like cell growth, cell cycle progression, ferroptosis and ER metabolic stress response. ASXL proteins activate BAP1 by forming the polycomb repressive deubiquitinase (PR-DUB) complex which acts on H2AK119ub1. Besides the ASXL proteins, BAP1 is known to interact with an established set of additional proteins.

Here, we identify novel BAP1 interacting proteins in the cytoplasm by expressing GFP-tagged BAP1 in an endogenous BAP1 deficient cell line using affinity purification followed by mass spectrometry (AP-MS) analysis. Among these novel interacting proteins are Histone acetyltransferase 1 (HAT1) and all subunits of the heptameric coat protein complex I (COPI) that is involved in vesicle formation and protein cargo binding and sorting. We validate that the HAT1 and COPI interactions occur at endogenous levels but find that this interaction with COPI is not mediated through the C-terminal KxKxx cargo sorting signals of the COPI complex.
Mechanistic insights into the success of xenobiotic degraders resolved from metagenomes of microbial enrichment cultures
Authors: Li Junhui , Jia Chongjian , Lu Qihong , Hungate Bruce A. , Dijkstra Paul , Wang Shanquan , Wu Cuiyu , Chen Shaohua , Li Deqiang , Shim Hojae
Published: March 2021

Even though microbial communities can be more effective at degrading xenobiotics than cultured micro-organisms, yet little is known about the microbial strategies that underpin xenobiotic biodegradation by microbial communities. Here, we employ metagenomic community sequencing to explore the mechanisms that drive the development of 49 xenobiotic-degrading microbial communities, which were enriched from 7 contaminated soils or sediments with a range of xenobiotic compounds. We show that multiple microbial strategies likely drive the development of xenobiotic degrading communities, notably (i) presence of genes encoding catabolic enzymes to degrade xenobiotics; (ii) presence of genes encoding efflux pumps; (iii) auxiliary catabolic genes on plasmids; and (iv) positive interactions dominate microbial communities with efficient degradation. Overall, the integrated analyses of microbial ecological strategies advance our understanding of microbial processes driving the biodegradation of xenobiotics and promote the design of bioremediation systems.
Comparative evaluation of plasma protein purification and 2-D gel electrophoresis protocols for analysis of HIV-1 infected human plasma proteins
Authors: Barik Sushanta Kumar , Varshney Deepika , Mohanty Keshar Kunja , Bisht Deepa , Patil Shripad A. , Singh Rananjay , Sharma Devesh , Tripathy SrikanthPrasad , Tandon Rekha , Singh Tej Pal , Jena Srikanta
Published: March 2021

Purification of proteins from human plasma is a herculean task to perform 2-D gel electrophoresis. Human plasma contains nearly 70% albumin and globulin. The removal of such high abundance high molecular weight proteins is very difficult before performing 2-D gel electrophoresis. It becomes more difficult when we intent to investigate in infectious diseases like HIV/AIDS. We tried to the best of our efforts adopting various organic and non-organic based protocols based on various published papers. After failure of these protocols in results of 2-D gel-electrophoresis Aurum serum mini kit (Bio-Rad, USA) was adopted for plasma protein purification for performing 2-D gel electrophoresis. The low-abundance proteins were better resolved by 10% SDS-PAGE in 2-D gel-electrophoresis. Then,we extended the MALDI-TOF/TOF analysis of low-abundance proteins in human plasma by adopting the Aurum serum mini kit (Bio-Rad, USA) for 2-D gel electrophoresis. Thus, we concluded that, depletion of high abundant proteins like albumin and globulin, the use of the Aurum serum mini kit (Bio-Rad, USA) is the protocol of choice to perform the 2-D gel electrophoresis of HIV-1 infected human plasma.
The enpp4 ectonucleotidase regulates kidney patterning signalling networks inXenopusembryos
Authors: Massé Karine , Bhamra Surinder , Paroissin Christian , Maneta-Peyret Lilly , Boué-Grabot Eric , Jones Elizabeth A.
Published: March 2021

The enpp ectonucleotidases regulate lipidic and purinergic signalling pathways by controlling the extracellular concentrations of purines and bioactive lipids. Although both pathways are key regulators of kidney physiology and linked to human renal pathologies, their roles during nephrogenesis remain poorly understood. We previously showed that the pronephros was a major site of enpp expression and now demonstrate an unsuspected role for the conserved vertebrate enpp4 protein during kidney formation inXenopus.Enpp4 over-expression results in ectopic renal tissues and, on rare occasion, complete mini-duplication of the entire kidney. Enpp4 is required and sufficient for expression of the pronephric markers and regulates the expression of RA, Notch and Wnt pathway members. Enpp4 is a membrane protein that binds, without hydrolyzing, phosphatidylserine and its effects are mediated by the receptor s1pr5, although not via the generation of S1P. Finally, we propose a novel and surprising non-catalytic mechanism by which lipidic signalling regulates nephrogenesis.
Mutation load decreases with haplotype age in wild Soay sheep
Authors: Stoffel M.A. , Johnston S.E. , Pilkington J.G. , Pemberton J.M
Published: March 2021

Runs of homozygosity (ROH) are pervasive in diploid genomes and expose the effects of deleterious recessive mutations, but how exactly these regions contribute to variation in fitness remains unclear. Here, we combined empirical analyses and simulations to explore the deleterious effects of ROH with varying genetic map lengths in wild Soay sheep. Using a long-term dataset of 4,592 individuals genotyped at 417K SNPs, we found that inbreeding depression increases with ROH length. A 1% genomic increase in long ROH (>12.5cM) reduced the odds of first-year survival by 12%, compared to only 7% for medium ROH (1.56-12.5cM), while short ROH (<1.56cM) had no effect on survival. We show by forward genetic simulations that this is predicted: compared with shorter ROH, long ROH will have higher densities of deleterious alleles, with larger average effects on fitness and lower population frequencies. Taken together, our results are consistent with the idea that the mutation load decreases in older haplotypes underlying shorter ROH, where purifying selection has had more time to purge deleterious mutations. Finally, our study demonstrates that strong inbreeding depression can persist despite ongoing purging in a historically small population.
Identification and predictability of soil quality factors and indicators from conventional soil and vegetation classifications
Authors: Simfukwe Paul , Hill Paul W. , Emmett Bridget A. , Jones Davey L.
Published: March 2021

Generally, the physical, chemical and biological attributes of a soil combined with abiotic factors (e.g. climate and topography) drive pedogenesis. However, biological indicators of soil quality play no direct role in traditional soil classification and surveys. To support their inclusion in classification schemes, previous studies have shown that soil type is a key factor determining microbial community composition in arable soils. This suggests that soil type could be used as proxy for soil biological function and vice versa. In this study we assessed the relationship between soil biological indicators with either vegetation cover or soil type. A wide range of soil attributes were measured on soils from across the UK to investigate whether; (1) appropriate soil quality factors (SQFs) and indicators (SQIs) can be identified, (2) soil classification can predict SQIs; (3) which soil quality indicators were more effectively predicted by soil types, and (4) to what extent do soil types and/ or aggregate vegetation classes (AVCs) act as major regulators of SQIs. Factor analysis was used to group 20 soil attributes into six SQFs namely;Soil organic matter,Organic matter humification,Soluble nitrogen,Microbial biomass,Reduced nitrogenandSoil humification index. Of these,Soil organic matterwas identified as the most important SQF in the discrimination of both soil types and AVCs. Among the measured soil attributes constituting theSoil organic matterfactor were, microbial quotient and bulk density were the most important attributes for the discrimination of both individual soil types and AVCs. TheSoil organic matterfactor discriminated three soil type groupings and four aggregate vegetation class groupings. Only the Peat soil and Heath and bog AVC were distinctly discriminated from other groups. All other groups overlapped with one another, making it practically impossible to define reference values for each soil type or AVC. We conclude that conventionally classified soil types cannot predict the SQIs (or SQFs), but can be used in conjunction with the conventional soil classifications to characterise the soil types. The two-way ANOVA showed that the AVCs were a better regulator of the SQIs than the soil types and that they (AVCs) presented a significant effect on the soil type differences in the measured soil attributes.
Scoping review of the applications of peptide microarrays on the fight against human infections
Authors: Vengesai Arthur , Kasambala Maritha , Mutandadzi Hamlet , Mduluza-Jokonya Tariro L. , Mduluza Takafira , Naicker Thajasvarie
Published: March 2021

Introduction

This scoping review explores the use of peptide microarrays in the fight against infectious diseases. The research domains explored included the use of peptide microarrays in the mapping of linear B-cell and T cell epitopes, antimicrobial peptide discovery, immunosignature characterisation and disease immunodiagnostics. This review also provides a short overview of peptide microarray synthesis.

Methods

Electronic databases were systematically searched to identify relevant studies. The review was conducted using the Joanna Briggs Institute methodology for scoping reviews and data charting was performed using a predefined form. The results were reported by narrative synthesis in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines.

Results

Eighty-six articles from 100 studies were included in the final data charting process. The majority (93%) of the articles were published during 2010–2020 and were mostly from Europe (44%) and North America (34 %). The findings were from the investigation of viral (44%), bacterial (30%), parasitic (25%) and fungal (2%) infections. Out of the serological studies, IgG was the most reported antibody type followed by IgM. The largest portion of the studies (78%) were related to mapping B-cell linear epitopes, 10% were on diagnostics, 9% reported on immunosignature characterisation and 6% reported on viral and bacterial cell binding assays. Two studies reported on T-cell epitope profiling.

Conclusion

The most important application of peptide microarrays was found to be B-cell epitope mapping or antibody profiling to identify diagnostic and vaccine targets. Immunosignatures identified by random peptide microarrays were found to be applied in the diagnosis of infections and interrogation of vaccine responses. The analysis of the interactions of random peptide microarrays with bacterial and viral cells using binding assays enabled the identification of antimicrobial peptides. Peptide microarray arrays were also used for T-cell linear epitope mapping which may provide more information for the design of peptide-based vaccines and for the development of diagnostic reagents.
NuA4 and SAGA acetyltransferase complexes cooperate for repair of DNA breaks by homologous recombination
Authors: Cheng Xue , Côté Valérie , Côté Jacques
Published: March 2021

Chromatin modifying complexes play important yet not fully defined roles in DNA repair processes. The essential NuA4 histone acetyltransferase (HAT) complex is recruited to double-strand break (DSB) sites and spreads along with DNA end resection. As predicted, NuA4 acetylates surrounding nucleosomes upon DSB induction and defects in its activity correlate with altered DNA end resection and Rad51 recombinase recruitment. Importantly, we show that NuA4 is also recruited to the donor sequence during recombination along with increased H4 acetylation, indicating a direct role during strand invasion/D-loop formation after resection. We found that NuA4 cooperates locally with another HAT, the SAGA complex, during DSB repair as their combined action is essential for DNA end resection to occur. This cooperation of NuA4 and SAGA is required for recruitment of ATP-dependent chromatin remodelers, targeted acetylation of repair factors and homologous recombination. Our work reveals a multifaceted and conserved cooperation mechanism between acetyltransferase complexes to allow repair of DNA breaks by homologous recombination.

Key Points

-NuA4-dependent acetylation modulates nucleosome dynamics to assist DNA end resection and strand invasion during homologous recombination.

-Combined recruitment and local action of NuA4 and SAGA acetyltransferase complexes is essential for DNA end resection.

-Cooperation between NuA4 and SAGA acetyltransferases is required for homologous recombination in eukaryotes.
Nonsterile immunity to cryptosporidiosis in infants is associated with mucosal IgA against the sporozoite and protection from malnutrition
Authors: Kabir Mamun , Alam Masud , Nayak Uma , Arju Tuhinur , Hossain Biplob , Tarannum Rubaiya , Khatun Amena , White Jennifer A. , Ma Jennie Z. , Haque Rashidul , Petri William A. , Gilchrist Carol A.
Published: March 2021

We conducted a longitudinal study of cryptosporidiosis from birth to three years of age in an urban slum of Dhaka Bangladesh. Fecal DNA was extracted from monthly surveillance samples and diarrheal stool samples collected from 392 infants from birth to three years. A pan-Cryptosporidium qPCR assay was used to identify sub-clinical and symptomatic cryptosporidiosis. Anthropometric measurements were collected quarterly to assess child nutritional status. 31% (121/392) of children experienced a single and 57% (222/392) multiple infections withCryptosporidium. Repeat infections had a lower burden of parasites in the stool (Cq slope = −1.85; p<0.0001) and were more likely to be sub-clinical (Chi square test for trend; p=0.01). Repeat infections were associated with the development of growth faltering (Pearson correlation = −0.18; p=0.0004). High levels of fecal IgA antibodies against theCryptosporidiumCp23 sporozoite protein at one year of life were associated with a delay in reinfection and amelioration of growth faltering through three years of life (HAZ IgA high responders −1.323 ± 0.932 versus HAZ −1.731 ± 0.984 p=0.0001). We concluded that nonsterile immunity to cryptosporidiosis in young children was associated with high levels of mucosal IgA anti-Cp23 and protection from diarrhea and growth faltering.

Authors Summary

Cryptosporidiumis one of the top causes of diarrhea and growth faltering in Bangladesh infants. We discovered that a prior infection resulted in incomplete immunity that protected from diarrhea and growth faltering but not infection and was associated with mucosal IgA against a sporozoite surface protein Cp23. The most important implication of these findings is that a cryptosporidiosis vaccine may not need to achieve complete protection from infection to have a beneficial impact on child health.
Constrained standardization of count data from massive parallel sequencing
Authors: Vanhoutven Joris , Cuypers Bart , Meysman Pieter , Hooyberghs Jef , Laukens Kris , Valkenborg Dirk
Published: March 2021

In high-throughput omics disciplines like transcriptomics, researchers face a need to assess the quality of an experiment prior to an in-depth statistical analysis. To efficiently analyze such voluminous collections of data, researchers need triage methods that are both quick and easy to use. Such a normalization method for relative quantitation, CONSTANd, was recently introduced for isobarically-labeled mass spectra in proteomics. It transforms the data matrix of abundances through an iterative, convergent process enforcing three constraints: (I) identical column sums; (II) each row sum is fixed (across matrices) and (III) identical to all other row sums. In this study, we investigate whether CONSTANd is suitable for count data from massively parallel sequencing, by qualitatively comparing its results to those of DESeq2. Further, we propose an adjustment of the method so that it may be applied to identically balanced but differently sized experiments for joint analysis. We find that CONSTANd can process large data sets with about 2 million count records in less than a second whilst removing unwanted systematic bias and thus quickly uncovering the underlying biological structure when combined with a PCA plot or hierarchical clustering. Moreover, it allows joint analysis of data sets obtained from different batches, with different protocols and from different labs but without exploiting information from the experimental setup other than the delineation of samples into identically processed sets (IPSs). CONSTANd’s simplicity and applicability to proteomics as well as transcriptomics data make it an interesting candidate for integration in multi-omics workflows.
Linguistic Analysis of the bioRxiv Preprint Landscape
Authors: Nicholson David N. , Rubinetti Vincent , Hu Dongbo , Thielk Marvin , Hunter Lawrence E. , Greene Casey S.
Published: March 2021

Preprints allow researchers to make their findings available to the scientific community before they have undergone peer review. Studies on preprints within bioRxiv have been largely focused on article metadata and how often these preprints are downloaded, cited, published, and discussed online. A missing element that has yet to be examined is the language contained within the bioRxiv preprint repository. We sought to compare and contrast linguistic features within bioRxiv preprints to published biomedical text as a whole as this is an excellent opportunity to examine how peer review changes these documents. The most prevalent features that changed appear to be associated with typesetting and mentions of supplementary sections or additional files. In addition to text comparison, we created document embeddings derived from a preprint-trained word2vec model. We found that these embeddings are able to parse out different scientific approaches and concepts, link unannotated preprint-peer reviewed article pairs, and identify journals that publish linguistically similar papers to a given preprint. We also used these embeddings to examine factors associated with the time elapsed between the posting of a first preprint and the appearance of a peer reviewed publication. We found that preprints with more versions posted and more textual changes took longer to publish. Lastly, we constructed a web application (https://greenelab.github.io/preprint-similarity-search/) that allows users to identify which journals and articles that are most linguistically similar to a bioRxiv or medRxiv preprint as well as observe where the preprint would be positioned within a published article landscape.
After migration into blood circulation, hematopoietic stem cells can stably self-renew and maintain bone marrow while being skewed toward myeloid lineage when submitted to serial transplantation
Authors: Even Yasmine , Yi Lin , Chang Chih-Kai , Rossi Fabio M.
Published: March 2021

Hematopoietic stem cells (HSCs) mainly reside in bone marrow (BM) within niches providing an appropriate environment for their survival and self-renewal. Although, small numbers of HSCs can quit their residing environment to migrate into blood circulation and re-engraft elsewhere in BM. Mobilizing agents such as granulocyte colony stimulating factor (G-CSF) can amplify this process by inducing massive HSC mobilization into blood circulation. This method is widely used in clinics to treat hematological disorders. However, in physiological conditions, the properties of HSCs after migration (called migratory HSCs) remain incompletely characterized. In this study, we investigated the capacity of migratory HSCs to self-renew, reconstitute and maintain BM. We show that after migration, HSCs can stably self-renew and maintain BM in homeostasis. However, while stably repopulating BM of irradiated recipients, migratory HSCs show a defect in lymphoid lineage reconstitution when subjected to serial transplantations. Our findings provide interesting knowledge on HSC properties after migration, which may benefits therapeutic research on HSC-based therapies to treat hematological disorders.
Underground Heterosis for Melons Yield
Authors: Dafna Asaf , Halperin Ilan , Oren Elad , Isaacson Tal , Tzuri Galil , Meir Ayala , Schaffer Arthur A , Burger Joseph , Tadmor Yaakov , Buckler Edward S. , Gur Amit
Published: March 2021

Heterosis, the superiority of hybrids over their parents, is a major genetic force associated with plant fitness and crop yield enhancement. Understanding and predicting heterosis is crucial for evolutionary biology, as well as for plant and animal breeding. We investigated root-mediated yield heterosis in melons (Cucumis melo) by characterizing common variety grafted onto 190 hybrid rootstocks resulting from crossing 20 diverse inbreds in a diallel-mating scheme. Hybrid rootstocks improved yield by more than 40% compared to their parents and the best hybrid outperformed the reference commercial variety by 65% under both optimal and minimal irrigation treatments. To characterize the genetics of the underground heterosis we conducted whole-genome re-sequencing of the 20 founder lines, and showed that parental genetic distance was no predictor for the level of heterosis. Through inference of the 190 hybrids genotypes from their parental genomes, followed by genome-wide association analysis, we mapped multiple root-mediated yield QTLs. The yield enhancement of the four best-performing hybrid rootstocks was validated in multiple experiments with four different scion varieties. While root biology is receiving increased attention, most of the research is conducted using plants not amenable to grafting and, as a result, it is difficult to separate root and shoot effects. Here, we use the rich genetic and genomic resources ofCucumis melo, where grafting is a common practice, to dissect a unique phenomenon of root-mediated yield heterosis, by directly evaluating in the field the contribution of the roots to fruit yield. Our grafting approach is inverted to the common roots genetics research path that focuses mainly on variation in root system architecture rather than the ultimate root-mediated whole-plant performance, and is a step towards discovery of candidate genes involved in root function and yield enhancement.

Highlight

We show that yield heterosis is significant in melon and controlled independently above and underground. Using common-scion grafting approach, we find that heritable rootstock-mediated variation in a diallel population is associated with substantial fruit yield heterosis.
Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2
Authors: Tayeb-Fligelman Einav , Cheng Xinyi , Tai Christen , Bowler Jeannette T. , Griner Sarah , Sawaya Michael R. , Seidler Paul M. , Jiang Yi Xiao , Lu Jiahui , Rosenberg Gregory M. , Salwinski Lukasz , Abskharon Romany , Zee Chih-Te , Hou Ke , Li Yan , Boyer David R. , Murray Kevin A. , Falcon Genesis , Anderson Daniel H. , Cascio Duilio , Saelices Lorena , Damoiseaux Robert , Guo Feng , Eisenberg David S.
Published: March 2021

The SARS-CoV-2 Nucleoprotein (NCAP) functions in RNA packaging during viral replication and assembly. Computational analysis of its amino acid sequence reveals a central low-complexity domain (LCD) having sequence features akin to LCDs in other proteins known to function in liquid–liquid phase separation. Here we show that in the presence of viral RNA, NCAP, and also its LCD segment alone, form amyloid-like fibrils when undergoing liquid–liquid phase separation. Within the LCD we identified three 6-residue segments that drive amyloid fibril formation. We determined atomic structures for fibrils formed by each of the three identified segments. These structures informed our design of peptide inhibitors of NCAP fibril formation and liquid–liquid phase separation, suggesting a therapeutic route for Covid-19.

One Sentence Summary

Atomic structures of amyloid-driving peptide segments from SARS-CoV-2 Nucleoprotein inform the development of Covid-19 therapeutics.
Multi–cell type gene coexpression network analysis reveals coordinated interferon response and cross–cell type correlations in systemic lupus erythematosus
Authors: Panwar Bharat , Schmiedel Benjamin J. , Liang Shu , White Brandie , Rodriguez Enrique , Kalunian Kenneth , McKnight Andrew J. , Soloff Rachel , Seumois Gregory , Vijayanand Pandurangan , Ay Ferhat
Published: March 2021

Systemic lupus erythematosus (SLE) is an incurable autoimmune disease disproportionately affecting women. A major obstacle in finding targeted therapies for SLE is its remarkable heterogeneity in clinical manifestations as well as in the involvement of distinct cell types. To identify cell-specific targets as well as cross-correlation relationships among expression programs of different cell types, we here analyze six major circulating immune cell types from SLE patient blood. Our results show that presence of an interferon response signature stratifies patients into two distinct groups (IFNneg vs. IFNpos). Comparing these two groups using differential gene expression and differential gene coexpression analysis, we prioritize a relatively small list of genes from classical monocytes including two known immune modulators:TNFSF13B/BAFF(target ofbelimumab, an approved therapeutic for SLE) andIL1RN(the basis ofanakinra,a therapeutic for rheumatoid arthritis). We then develop a multi–cell type extension of the weighted gene coexpression network analysis (WGCNA) framework, termed mWGCNA. Applying mWGCNA to RNA-seq data from six sorted immune cell populations (15 SLE, 10 healthy donors), we identify a coexpression module with interferon-stimulated genes (ISGs) among all cell types and a cross–cell type correlation linking expression of specific T helper cell markers to B cell response as well as toTNFSF13Bexpression from myeloid cells, all of which in turn correlates with disease severity of IFNpos patients. Our results demonstrate the power of a hypothesis-free and data-driven approach to discover drug targets and to reveal novel cross-correlation across cell types in SLE with implications for other autoimmune diseases.
AP-1 subunits converge promiscuously at enhancers to potentiate transcription
Authors: Seo Jungkyun , Koçak D. Dewran , Bartelt Luke C. , Williams Courtney A. , Barrera Alejandro , Gersbach Charles A. , Reddy Timothy E.
Published: March 2021

The AP-1 transcription factor (TF) dimer contributes to many biological processes and environmental responses. AP-1 can be composed of many interchangeable subunits. Unambiguously determining the binding locations of these subunits in the human genome is challenging because of variable antibody specificity and affinity. Here, we definitively establish the genome-wide binding patterns of five AP-1 subunits by using CRISPR to introduce a common antibody tag on each subunit. We find limited evidence for strong dimerization preferences between subunits at steady state and find that, under a stimulus, dimerization patterns reflect changes in the transcriptome. Further, our analysis suggests that canonical AP-1 motifs indiscriminately recruit all AP-1 subunits to genomic sites, which we term AP-1 hotspots. We find that AP-1 hotspots are predictive of cell type–specific gene expression and of genomic responses to glucocorticoid signaling (more so than super-enhancers) and are significantly enriched in disease-associated genetic variants. Together, these results support a model where promiscuous binding of many AP-1 subunits to the same genomic location play a key role in regulating cell type–specific gene expression and environmental responses.
Management accounting systems to support stressing events: evidence from the food sector
Authors: Truant Elisa , Broccardo Laura , Culasso Francesca , Vrontis Demetris
Published: March 2021

Purpose

This study analyses how family-run businesses operating in the Italian food sector faced the ongoing COVID-19 pandemic that affected the global economy, with the support of management accounting systems.

Design/methodology/approach

The methodology used is based on a survey questionnaire conducted on Italian family firms involved in food business. Both qualitative and quantitative data were collected and analysed.

Findings

This study categorised the companies into three groups, according to their long-term orientation and the use of management accounting tools. The results highlight proactive versus passive companies that emphasise various recovery paths from the perspective of performance.

Research limitations/implications

Limitations refer to the attention on a single country and the sample size.

Practical implications

The main practical implication refers to management at different levels that should better understand how a clear long-term orientation can maintain the competitive position and pre-crisis performance.

Originality/value

This study examines the measures launched by companies to address challenges originating from the COVID-19 pandemic.
Inulin enhances nutritional, sensorial and technological characteristics of synbiotic yogurt drink
Authors: Soh Joshua Ie Xin , Wilian Malvino , Yan See Wan
Published: March 2021

Purpose

In recent years, global demand for functional foods grew tremendously due to the rising trend of health-conscious consumers. Driven by increased awareness of probiotic products, consumption of yogurt drink is gaining popularity across all age groups. In the present study, the authors aimed to assess sensorial, nutritional and technological properties of synbiotic yogurt drink enriched with prebiotic inulin.

Design/methodology/approach

Sensory analysis, proximate compositions, viscosity, viable count and DPPH radical scavenging activity were examined in control (without inulin) and 3 variants of inulin-supplemented synbiotic yogurt drink, namely F1 (4%, inulin), F2 (4.5% inulin) and F3 (5% inulin).

Findings

Evaluated by 75 consumer panellists on 9-point hedonic scales, F3 showed significantly (p < 0.05) higher overall acceptability (5.79 ± 1.94) compared to control. In addition to lower calorie content (36.52 kcal/100 ml), nutritional and technological properties of F3 [total dietary fibre content (4.03 ± 0.04 g/100 ml), viscosity (28 ± 6.93 cP), viable count (87.00 ± 4.00 × 106 CFU/ml S. thermophilus; 14.67 ± 3.51 × 106 CFU/ml L. bulgaricus) and antioxidant activity (50.40 ± 1.80%)] were significantly (p < 0.05) improved compared to control. Remarkably, the new formulation complied with nutrient criteria for Healthier Choice Logo Malaysia in addition to meeting requirements for “low fat” and “high dietary fibre” contents according to Malaysia Guide to Nutrition Labelling and Claims. Hence, we conclude that 5% inulin improved nutritional and technological characteristic in synbiotic yogurt drink without compromising consumers' acceptance.

Originality/value

This novel study showcases the incorporation of prebiotic inulin in the development of synbiotic yogurt drink. Remarkably, this new formulation complied with the nutrient criteria for Healthier Choice Logo Malaysia in addition to meeting the requirements for “low fat” and “high dietary fibre” contents according to Malaysia Guide to Nutrition Labelling and Claims. More importantly, results have contributed knowledge to existing literature as well as benefits food manufacturers in creating healthy yogurt drinks to better meet the needs and expectations of health-conscious consumers without compromising hedonic perceptions.
ERP software selection using intuitionistic fuzzy and interval grey number-based MACBETH method
Authors: Yurtyapan Mustafa Said , Aydemir Erdal
Published: March 2021

Purpose

Enterprise Resource Planning (ERP) software which is a knowledge-based design on the interconnective communication of business units and information share, ensures that business processes such as finance, production, purchasing, sales, logistics and human resources, are integrated and gathered under one roof. This integrated system allows the company to make fast and accurate decisions and increases its competitiveness. Therefore, for an enterprise, choosing the suitable ERP software is extremely important. The aim of this study is to present new research on the ERP software selection process by clarifying the uncertainties and find suitable software in a computational way.

Design/methodology/approach

ERP selection problem design includes uncertainties on the expert opinions and the criteria values using intuitionistic fuzzy set theory and interval grey-numbers to MACBETH multi criteria decision making method. In this paper, a new interval grey MACBETH method approach is proposed, and the degree of greyness approach is used for clarifying the uncertainties. Using this new approach in which grey numbers are used, it is aimed to observe the changes in the importance of the alternatives. Moreover, the intuitionistic fuzzy set method is applied by considering the importance of expert opinions separately.

Findings

The proposed method is based on quantitative decision making derived from qualitative judgments. The results given under uncertain conditions are compared with the results obtained under crisp conditions of the same methods. With the qualitative levels of experts reflected in the decision process, it is clearly seen that ERP software selection problem area has more effective alternative decision solutions to the uncertain environment, and decision makers should not undervalue the unsteadiness of criteria during ERP software selection process.

Originality/value

This study contributes to the relevant literature by (1) utilizing the MACBETH method in the selection of the ERP software by optimization, and (2) validating the importance of expert opinions with uncertainties on a proper ERP software selection procedure. So, the findings of this study can help the decision-makers to evaluate the ERP selection in uncertain conditions.
Hybrid multibeam forming and multiuser detection technique for MU-MIMO system
Authors: Kumari D. Lalitha , Prasad M.N. Giri
Published: March 2021

Purpose

In recent years, multiuser-multiple-input multiple-output (MU-MIMO)-based wireless communication system has emerged as a prominent 5G technique that has several advantages over conventional MIMO systems such as high data rate and channel capacity. In this paper, the authors introduce a novel low-complexity radix factorization-based fast Fourier transform (FFT) as a multibeamformer and maximal likelihood-MU detection (ML-MUD) techniques as an optimal signal subdetector which results with considerable complexity reduction with intolerable error rate performance.

Design/methodology/approach

The proposed radix-factorized FFT-multibeamforming (RF-FFT-MBF) architectures have the potential to reduce both hardware complexity and energy consumptions as compared to its state-of-the-art methods while meeting the throughput requirements of emerging 5G devices. Here through simulation results, the efficiency of the scaled ML subdetector system is compared with the conventional ML detectors.

Findings

Here through simulation results, the efficiency of the scaled ML subdetector system is compared with the conventional ML detectors. Through experimental results, it is well proved that the proposed detector offers significant hardware and energy efficiency with the least possible error rate performance overhead.

Originality/value

Here through simulation results, the efficiency of the scaled ML subdetector system is compared with the conventional ML detectors. Through experimental results, it is well proved that the proposed detector offers significant hardware and energy efficiency with the least possible error rate performance overhead.
Decoding the dark shades of electronic human resource management
Authors: Gupta Manish , Hassan Yusuf , Pandey Jatin , Kushwaha Ankur
Published: March 2021

Purpose

While prior studies have highlighted the brighter side of technology adoption in improving human resource (HR) functions, the dark side pertaining to the adoption of technology in people management within organizations has gone relatively unnoticed. The current study tries to demystify the dark side of electronic human resource management (e-HRM) by examining banking institutions in India which are believed to have undergone several transformations in recent years.

Design/methodology/approach

This study adopts an inductive qualitative approach to examine the research problem. In total, 53 semi-structured interviews were conducted with the employees of eight public sector banks in India. The interviews were transcribed. The analysis of the data was done using the thematic analysis technique.

Findings

The findings of the study suggest that there is a stratification of the workplace in banking institutions into digital natives and digital migrants. This social stratification is based on technology adoption and usage which has further created problems in the form of knowledge hiding and perceived workplace conflicts.

Practical implications

The findings of the current study have important theoretical and managerial implications. It not only extends the current scholarship on the transtheoretical model of change but it also has strong managerial implications as it highlights the need for the adoption of customized e-HRM training curriculums for the workforce based on their age, education, work experience and expertise.

Originality/value

Current research on the dark side of e-HRM is inadequate. Furthermore, the evolution of banking institutions from being a typical bureaucratic organization into a hybrid one has not been examined in the context of e-HRM.
Host–microbial systems as glass cannons: Explaining microbiome stability in corals exposed to extrinsic perturbations
Authors: Dunphy Courtney M. , Vollmer Steven V. , Gouhier Tarik C.
Published: March 2021

Although stability is relatively well understood in macro‐organisms, much less is known about its drivers in host–microbial systems where processes operating at multiple levels of biological organisation jointly regulate the microbiome.

We conducted an experiment to examine the microbiome stability of three Caribbean corals (Acropora cervicornis, Pseudodiploria strigosa and Porites astreoides) by placing them in aquaria and exposing them to a pulse perturbation consisting of a large dose of broad‐spectrum antibiotics before transplanting them into the field.

We found that coral hosts harboured persistent, species‐specific microbiomes. Stability was generally high but variable across coral species, with A. cervicornis microbiomes displaying the lowest community turnover in both the non‐perturbed and the perturbed field transplants. Interestingly, the microbiome of P. astreoides was stable in the non‐perturbed field transplants, but unstable in the perturbed field transplants.

A mathematical model of host–microbial dynamics helped resolve this paradox by showing that when microbiome regulation is driven by host sanctioning, both resistance and resilience to invasion are low and can lead to instability despite the high direct costs bourne by corals. Conversely, when microbiome regulation is mainly associated with microbial processes, both resistance and resilience to invasion are high and promote stability at no direct cost to corals. We suggest that corals that are mainly regulated by microbial processes can be likened to ‘glass cannons’ because the high stability they exhibit in the field is due to their microbiome's potent suppression of invasive microbes. However, these corals are susceptible to destabilisation when exposed to perturbations that target the vulnerable members of their microbiomes who are responsible for mounting such powerful attacks against invasive microbes. The differential patterns of stability exhibited by P. astreoides across perturbed and non‐perturbed field transplants suggest it is a ‘glass cannon’ whose microbiome is regulated by microbial processes, whereas A. cervicornis’ consistent patterns of stability suggest that its microbiome is mainly regulated by host‐level processes.

Our results show that understanding how processes that operate at multiple levels of biological organisation interact to regulate microbiomes is critical for predicting the effects of environmental perturbations on host–microbial systems.
Why are the affluent better represented around the world?
Authors: LUPU NOAM , WARNER ZACH
Published: March 2021

Scholars have discovered remarkable inequalities in who gets represented in electoral democracies. Around the world, the preferences of the rich tend to be better represented than those of the less well‐off. In this paper, we use the most comprehensive comparative dataset of unequal representation available to answer why the poor are underrepresented. By leveraging variation over time and across countries, we study which factors explain why representation is more unequal in some places than in others. We compile a number of covariates examined in previous studies and use machine learning to describe which mechanisms best explain the data. Globally, we find that economic conditions and good governance are most important in determining the extent of unequal representation, and we find little support for hypotheses related to political institutions, interest groups or political behaviour, such as turnout. These results provide the first broadly comparative explanations for unequal representation.
Effect of hydrocolloid coatings (Basil seed gum, xanthan, and methyl cellulose) on the mass transfer kinetics and quality of fried potato strips
Authors: Zamani‐Ghalehshahi Atefeh , Farzaneh Parisa
Published: March 2021

In this research, the effect of different temperatures (160, 180, and 190 °C) and hydrocolloid coatings (Basil seed gum [BSG], xanthan gum [XG], methylcellulose [MC], BSG–XG, and BSG–MC mixtures) were investigated on the physicochemical properties (oil uptake, moisture loss, color, microscopic structure, activation energy, and texture), mass transfer kinetic of fried potato strips in deep‐fat frying, and oil partitions using frying and postfrying cooling phase. An increase in frying time reduced the moisture content and hardness of potato strips; however, the oil content and color difference increased. The oil content in the coated samples had lower rates than that in the noncoated ones. The treated samples using BSG–xanthan mixture (50:50) and BSG had the lowest oil uptake at 0.13% and 0.14% Dry basis (d.b.), respectively. The maximum and minimum values of effective moisture diffusivity were measured in control and samples coated with BSG–XG and BSG, respectively. As frying temperature increased, the specific rate of oil uptake increased and the equilibrium oil content decreased. Overall, BSG–XG mixture–coated potato strips can be used as a promising product due to absorbing the lowest oil rate and being similar to the control in terms of organoleptic properties.