bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of High-Fat Diet on Carcinogen-Induced Pancreatic Cancer and Intestinal Microbiota in C57BL/6 Wild-Type Mice
Authors: Liu Beibei , Wang Furong , Chen Lina , Xin Yi , Liu Likun , Wu Dachang , Li Weiling
Published: May 2021

Objectives

High-fat diet has been considered a risk factor for the development of pancreatic cancer. It is also shown to significantly impact composition and dysbiosis of gut microbiota in both humans and animals. However, there is little information on the effect of high-fat diet on the development of pancreatic cancer or upon the gut microbiota of patients with pancreatic cancer in humans or animal models.

Methods

In this study, the effect of high-fat diet on cancer pathology and the gut microbiota was investigated by a carcinogen-induced pancreatic cancer mouse model.

Results

Compared with carcinogen alone, mice with high-fat diet and carcinogen showed more obvious pathological changes in pancreatic tissue; increased levels of proinflammatory cytokine tumor necrosis factor-α, interleukin-6, interleukin-10, and carbohydrate antigen 242; and increased expression of cancer-associated biomarkers mucin-4 and claudin-4 in pancreatic tissue. Moreover, there is a significant change in the gut microbiota between the carcinogen group and the carcinogen with high-fat diet group. We identified that Johnsonella ignava especially existed in the carcinogen with high-fat diet group, which may contribute to pancreatic cancer development.

Conclusions

Our results revealed that high-fat diet changed the composition of the gut microbiota and was involved in carcinogen-induced pancreatic cancer progression.
Froin Syndrome, a Rare Complication of Multiple Myeloma
Authors: Nizam Ahmad , Sivakumar Keithan , Yacoub Hussam
Published: May 2021

Introduction:

Froin syndrome is a rare condition that is defined as marked coagulability, elevated protein level, and xanthochromia of the cerebrospinal fluid (CSF). Froin syndrome more commonly occurs because of obstruction of CSF flow due to underlying inflammatory or neoplastic conditions.

Case Report:

We present a case of a 38-year-old man who was found to have Froin syndrome a year after he was diagnosed with multiple myeloma (MM). CSF analysis, laboratory work-up, and magnetic resonance imaging of the neuroaxis supported the diagnosis of Froin syndrome related to leptomeningeal myelomatosis. To our knowledge, this is the first reported case of FS due to MM.

Conclusion:

Leptomeningeal myelomatosis associated with MM can cause blockage of CSF circulation leading to Froin syndrome. Inflammatory or neoplastic conditions should be considered as an underlying etiology.
COVID-19–Associated Ischemic Stroke in a Patient on Therapeutic Anticoagulation
Authors: Scharpf William , Katsafanas Constance , Ng Kintin
Published: May 2021

Introduction:

The coronavirus disease 2019 (COVID-19) has been associated with a hypercoagulable state, increasing the risk for ischemic stroke. In select cases, patients are already on anticoagulation therapy. Such examples highlight the severity of COVID-19’s hyperthrombotic state, and raise questions regarding optimal stroke prevention in these patients.

Case Report:

An 84-year-ool male with past medical history of chronic obstructive pulmonary disease, hypertension, and paroxysmal atrial fibrillation was admitted for respiratory failure secondary to COVID-19 pneumonia. He was continued on his home apixaban 5 mg twice daily. On day 2 of admission, he developed a new aphasia, and right-sided facial droop. Computed tomography (CT) head was unrevealing. CT angiography did not show large vessel occlusion. CT perfusion demonstrated a left middle cerebral artery ischemic penumbra, without core. He was not eligible for thrombolysis or thrombectomy interventions. Later CT head confirmed L middle cerebral artery infarct. The patient’s D-dimer was 1,184 ng/mL on day 1 of admission, and increased to 111,574 by day 4. His hypoxia worsened, requiring intubation and transfer to the ICU. He experienced further clinical decline and eventual demise.

Conclusion:

Ischemic stroke in anticoagulated patients with COVID-19 has been previously reported. Such cases emphasize the severity of the coronavirus virus associated hypercoagulable state. A majority of reported cases have occurred in patients continuing their ambulatory therapy. Overall, such cases are likely underreported. There are current trials comparing therapeutic versus prophylactic dose anticoagulation in patients with COVID-19. There are no studies specifically addressing anticoagulation agent failure in these patients. Further research is required this area to determine the optimal therapy for patients with COVID-19.
Direct identification and molecular characterization of zoonotic hazards in raw milk by metagenomics using Brucella as a model pathogen
Authors: Grützke Josephine , Gwida Mayada , Deneke Carlus , Brendebach Holger , Projahn Michaela , Schattschneider Alexander , Hofreuter Dirk , El-Ashker Maged , Malorny Burkhard , Al Dahouk Sascha
Published: May 2021

Metagenomics is a valuable diagnostic tool for enhancing microbial food safety because (i) it enables the untargeted detection of pathogens, (ii) it is fast since primary isolation of micro-organisms is not required, and (iii) it has high discriminatory power allowing for a detailed molecular characterization of pathogens. For shotgun metagenomics, total nucleic acids (NAs) are isolated from complex samples such as foodstuff. Along with microbial NAs, high amounts of matrix NAs are extracted that might outcompete microbial NAs during next-generation sequencing and compromise sensitivity for the detection of low abundance micro-organisms. Sensitive laboratory methods are indispensable for detecting highly pathogenic foodborne bacteria like

Brucella

spp., because a low infectious dose is sufficient to cause human disease through the consumption of contaminated dairy or meat products. In our study, we applied shotgun metagenomic sequencing for the identification and characterization of

Brucella

spp. in artificially and naturally contaminated raw milk from various ruminant species. With the depletion of eukaryotic cells prior to DNA extraction,

Brucella

was detectable at 10 bacterial cells ml−1, while at the same time microbiological culture and isolation of the fastidious bacteria commonly failed. Moreover, we were able to retrieve the genotype of a

Brucella

isolate from a metagenomic dataset, indicating the potential of metagenomics for outbreak investigations using SNPs and core-genome multilocus sequence typing (cgMLST). To improve diagnostic applications, we developed a new bioinformatics approach for strain prediction based on SNPs to identify the correct species and define a certain strain with only low numbers of genus-specific reads per sample. This pipeline turned out to be more sensitive and specific than Mash Screen. In raw milk samples, we simultaneously detected numerous other zoonotic pathogens, antimicrobial resistance genes and virulence factors. Our study showed that metagenomics is a highly sensitive tool for biological risk assessment of foodstuffs, particularly when pathogen isolation is hazardous or challenging.
American older adults in COVID-19 Times:Vulnerability types, aging attitudes and emotional responses
Authors: Fu Mingqi , Guo Jing , Chen Xi , Zhang Qilin
Published: May 2021

Background

The coronavirus disease aroused challenges to the emotional well-being of vulnerable older adults in hard-hit areas. This study investigates different vulnerability types among American older adults and how modes of vulnerability are associated with aging attitudes and emotional responses.

Methods

Using Latent Class Analysis, we investigated 2003 respondents aged over 50 from HRS. Hierarchical linear regressions with the affective profile as cluster identity were used to examine the relationship between vulnerability type and positive aging attitudes with positive and negative emotional responses.

Results

We detected three vulnerability types among American older adults: the slight vulnerability (72%), the healthcare use vulnerability (19%), and the dual vulnerabilities (9%). No significant difference in positive emotions was found between vulnerability types. However, more negative emotions were found among older adults with healthcare use vulnerability (B=0.746, SE=0.759) and dual vulnerabilities (B=1.186, SE=0.274) than those with slight vulnerability. Positive aging attitudes associate with more positive emotions (B=0.266, SE=0.017) but less negative emotions (B=-0.183, SE=0.016) and had significant moderation effects on the relationship between vulnerability types and negative emotional responses (B=-0.118, SE=0.045).

Conclusion

Older adults’ emotional well-being should not be neglected as they deserve the support of prevention and intervention strategies, in particular when they have vulnerabilities in healthcare use and financial sustainment. Female, non-white races, and those aged below 65, been uncoupled, less educated, and with ADL difficulties should prioritize.
Germline RUNX1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia
Authors: Li Yizhen , Devidas Meenakshi , Yang Wentao , Winter Stuart S. , Yang Wenjian , Dunsmore Kimberly P. , Smith Colton , Qian Maoxiang , Zhao Xujie , Zhang Ranran , Gastier-Foster Julie M. , Raetz Elizabeth A. , Carroll William L. , Li Chunliang , Liu Paul P. , Rabin Karen R. , Sanda Takaomi , Mullighan Charles G. , Nichols Kim E. , Evans William E. , Pui Ching-Hon , Hunger Stephen P. , Teachey David T. , Relling Mary V. , Loh Mignon L. , Yang Jun J.
Published: May 2021

RUNX1 is a transcription factor critical for definitive hematopoiesis and genetic alterations in RUNX1 have been implicated in both benign and malignant blood disorders, particularly of the megakaryocyte and myeloid lineages. Somatic RUNX1 mutations are reported in B- and T-cell acute lymphoblastic leukemia (B-ALL and T-ALL), but germline genetic variation of RUNX1 in these lymphoid malignancies have not been comprehensively investigated. Sequencing 4,836 children with B-ALL and 1,354 cases of T-ALL, we identified 31 and 18 unique germline RUNX1 variants in these two ALL subtypes, respectively. RUNX1 variants in B-ALL were predicted to have minimal impact. By contrast, 54.5% of variants in T-ALL result in complete or partial loss of RUNX1 activity as a transcription activator in vitro, with dominant negative effects for 4 variants. Ectopic expression of dominant negative deleterious RUNX1 variants in human CD34+ cells repressed differentiation into erythroid, megakaryocytes, and T cells, while promoting differentiation towards myeloid cells. We then performed chromatin immunoprecipitation profiling in isogenic T-ALL models with variants introduced by genome editing of endogenous RUNX1. We observed highly distinctive patterns of DNA binding and target genomic loci by RUNX1 proteins encoded by the truncating vs missense variants. The p.G365R RUNX1 variant resulted in a novel methylation site in RUNX1 and alteration in its interaction with CBFβ. Further whole genome sequencing showed that JAK3 mutation was the most frequent somatic genomic abnormality in T-ALL with germline RUNX1 variants. Consistently, co-introduction of RUNX1 variant and JAK3 mutation in hematopoietic stem and progenitor cells in mouse gave rise to T-ALL with early T-cell precursor phenotype in vivo, compared to thymic T-ALL seen in mice with JAK3 mutation alone. Taken together, these results indicated that RUNX1 is an important predisposition gene for ALL, especially in T-ALL and also pointed to novel biology of RUNX1-mediated leukemogenesis in the lymphoid lineages.
Tracking the emergence of disparities in the subnational spread of COVID-19 in Brazil using an online application for real-time data visualisation: a longitudinal analysis
Authors: Mee Paul , Alexander Neal , Mayaud Philippe , Colon Gonzalez Felipe de Jesus , Abbott Sam , de Souza Santos Andreza Aruska , Acosta Andre Luis , Parag Kris V. , Pereira Rafael H. M. , Prete Carlos A. , Sabino Ester C. , Faria Nuno R. ,   LSHTM Centre for Mathematical Modelling of Infectious Disease COVID-19 working group, Brady Oliver J
Published: May 2021

Background

Brazil is one of the countries worst affected by the COVID-19 pandemic with over 20 million cases and 557,000 deaths reported. Comparison of real-time local COVID-19 data between areas is essential for understanding transmission, measuring the effects of interventions and predicting the course of the epidemic, but are often challenging due to different population sizes and structures.

Methods

We describe the development of a new app for the real-time visualisation of COVID-19 data in Brazil at the municipality level. In the CLIC-Brazil app, daily updates of case and death data are downloaded, age standardised and used to estimate reproduction number (Rt). We show how such platforms can perform real-time regression analyses to identify factors associated with the rate of initial spread and early reproduction number. We also use survival methods to predict the likelihood of occurrence of a new peak of COVID-19 incidence.

Findings

After an initial introduction in São Paulo and Rio de Janeiro states in early March 2020, the epidemic spread to Northern states and then to highly populated coastal regions and the Central-West. Municipalities with higher metrics of social development experienced earlier arrival of COVID-19 (decrease of 11·1 days [95% CI:13·2,8·9] in the time to arrival for each 10% increase in the social development index). Differences in the initial epidemic intensity (meanRt) were largely driven by geographic location and the date of local onset.

Interpretation

This study demonstrates that platforms that monitor, standardise and analyse the epidemiological data at a local level can give useful real-time insights into outbreak dynamics that can be used to better adapt responses to the current and future pandemics.

Funding

This project was supported by a Medical Research Council UK (MRC-UK) -São Paulo Research Foundation (FAPESP) CADDE partnership award (MR/S0195/1 and FAPESP 18/14389-0)
SARS-CoV-2 spike protein induces brain pericyte immunoreactivity in absence of productive viral infection
Authors: Khaddaj-Mallat Rayan , Aldib Natija , Paquette Anne-Sophie , Ferreira Aymeric , Lecordier Sarah , Bernard Maxime , Saghatelyan Armen , ElAli Ayman
Published: May 2021

COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 pathogenesis causes vascular-mediated neurological disorders via still elusive mechanisms. SARS-CoV-2 infects host cells by binding to angiotensin-converting enzyme 2 (ACE2), a transmembrane receptor that recognizes the viral spike (S) protein. Brain pericytes were recently shown to express ACE2 at the neurovascular interface, outlining their possible implication in microvasculature injury in COVID-19. Yet, pericyte responses to SARS-CoV-2 is still to be fully elucidated. Using cell-based assays, we report that ACE2 expression in human brain vascular pericytes is highly dynamic and is increased upon S protein stimulation. Pericytes exposed to S protein underwent profound phenotypic changes translated by increased expression of contractile and myofibrogenic proteins, namely α-smooth muscle actin (α-SMA), fibronectin, collagen I, and neurogenic locus notch homolog protein-3 (NOTCH3). These changes were associated to an altered intracellular calcium (Ca2+) dynamic. Furthermore, S protein induced lipid peroxidation, oxidative and nitrosative stress in pericytes as well as triggered an immune reaction translated by activation of nuclear factor-kappa-B (NF-κB) signalling pathway, which was potentiated by hypoxia, a condition associated to vascular comorbidities, which exacerbate COVID-19 pathogenesis. S protein exposure combined to hypoxia enhanced the production of pro-inflammatory cytokines involved in immune cell activation and trafficking, namely interleukin-8 (IL-8), IL-18, macrophage migration inhibitory factor (MIF), and stromal cell-derived factor-1 (SDF-1). Finally, we found that S protein could reach the mouse brain via the intranasal route and that reactive ACE2-expressing pericytes are recruited to the damaged tissue undergoing fibrotic scarring in a mouse model of cerebral multifocal micro-occlusions, a main reported vascular-mediated neurological condition associated to COVID-19. Our data demonstrate that the released S protein is sufficient to mediate pericyte immunoreactivity, which may contribute to microvasculature injury in absence of a productive viral infection. Our study provides a better understanding for the possible mechanisms underlying cerebrovascular disorders in COVID-19, paving the way to develop new therapeutic interventions.
Re-oxidation of cytosolic NADH is a major contributor to the high oxygen requirements of the thermotolerant yeastOgataea parapolymorphain oxygen-limited cultures
Authors: Dekker Wijbrand J. C. , Juergens Hannes , Ortiz-Merino Raúl A. , Mooiman Christiaan , van den Berg Remon , Kaljouw Astrid , Mans Robert , Pronk Jack T.
Published: May 2021

Thermotolerance is an attractive feature for yeast-based industrial ethanol production. However, incompletely understood oxygen requirements of known thermotolerant yeasts are incompatible with process requirements. To study the magnitude and molecular basis of these oxygen requirements in the facultatively fermentative, thermotolerant yeastOgataea parapolymorpha, chemostat studies were performed under defined oxygen-sufficient and oxygen-limited cultivation regimes. The minimum oxygen requirements ofO. parapolymorphawere found to be at least an order of magnitude larger than those of the thermotolerant yeastKluyveromyces marxianus. This high oxygen requirement coincided with absence of glycerol formation, which plays a key role in NADH reoxidation in oxygen-limited cultures of other facultatively fermentative yeasts. Co-feeding of acetoin, whose reduction to 2,3-butanediol can reoxidize cytosolic NADH, supported a 2.5-fold higher biomass concentration in oxygen-limited cultures. The apparent inability ofO. parapolymorphato produce glycerol correlated with absence of orthologs of theS. cerevisiaegenes encoding glycerol-3P phosphatase (ScGPP1, ScGPP2). Glycerol production was observed in aerobic batch cultures of a strain in which genes including key enzymes in mitochondrial reoxidation of NADH were deleted. However, transcriptome analysis did not identify a clear candidate for the responsible phosphatase. Expression of ScGPD2, encoding NAD+-dependent glycerol-3P dehydrogenase, and ScGPP1inO. parapolymorpharesulted in increased glycerol production in oxygen-limited chemostats, but glycerol production rates remained substantially lower than observed inS. cerevisiaeandK. marxianus. These results identify a dependency on aerobic respiration for reoxidation of NADH generated in biosynthesis as a key factor in the unexpectedly high oxygen requirements ofO. parapolymorpha.

Importance

Thermotolerant yeasts hold great potential for anaerobic fermentation processes but their application is so far hampered by incompletely understood oxygen requirements. Based on quantitative physiological studies in oxygen-limited chemostat cultures, this study shows that the thermotolerant yeastOgataea parapolymorphahas a much higher oxygen requirement than other, previously investigated facultatively fermentative yeasts. The large oxygen requirement ofO. parapolymorphawas linked to an inability of oxygen-limited cultures to efficiently reoxidize NADH formed in biosynthetic processes by glycerol formation. These results provide a basis for reducing the oxygen requirements ofO. parapolymorphaby targeted metabolic engineering. In addition, this study shows that diversity of oxygen requirements should be taken into account in selecting yeast species for application in anaerobic or oxygen-limited industrial processes.
Latest Generation Colonoscope Yields Improvements in Cecal Insertion Time and Adenoma Detection Rate: A Retrospective Comparison of Two Colonoscope Brands
Authors: Yasmeh Pauline , Vicari Joseph J. , Shiels Aaron J.
Published: May 2021

Background and Aims

High quality colonoscopy remains the cornerstone of colon cancer prevention. Studies have shown that generational advances in colonoscopes result in more favorable clinical outcomes. Performance of various endoscopes is determined using objective quality measures. The aim of this study was to compare these measures between two colonoscope platforms.

Methods

This study is a single center retrospective study of 3,761 patients undergoing initial screening colonoscopy between November 2013 and May 2020 using two different colonoscope platforms (Fujifilm EC-760R-V/L, n=2287 and Olympus CF and PCF 180 series, n= 1474). The primary outcomes measured were cecal insertion time, withdrawal time, and adenoma detection rate.

Results

Procedures completed with the Fujifilm colonoscope had mean cecal insertion times that were 2.01 minutes shorter than procedures completed with Olympus (p<.0001). Procedures completed with Olympus brand colonoscopes had prolonged cecal insertion times (≥10 minutes) nearly three times as often compared to those performed with Fujifilm colonoscopes (p<.0001). Cecal withdrawal times were slightly longer for females performed with Fujifilm colonoscopes, but there was no difference when all procedures were included (p=.09). Procedures completed with Fujifilm colonoscopes had higher adenoma detection rates compared to those completed with Olympus colonoscopes (p<0.001).

Conclusions

In this study, Fujifilm colonoscopes outperformed Olympus colonoscopes in screening colonoscopies with statistically and clinically significant shorter cecal insertion times and higher adenoma detection, though both platforms had similar withdrawal times.
Protective heterologous T cell immunity in COVID-19 induced by MMR and Tdap vaccine antigens
Authors: Mysore Vijayashree , Cullere Xavier , Settles Matthew L. , Ji Xinge , Kattan Michael W. , Desjardins Michaël , Durbin-Johnson Blythe , Gilboa Tal , Baden Lindsey R. , Walt David R. , Lichtman Andrew , Jehi Lara , Mayadas Tanya N.
Published: May 2021

T cells are critical for control of viral infection and effective vaccination. We investigated whether prior Measles-Mumps-Rubella (MMR) or Tetanus-Diphtheria-pertussis (Tdap) vaccination elicit cross-reactive T cells that mitigate COVID-19. Using co-cultures of antigen presenting cells (APC) loaded with antigens and autologous T cells, we found a high correlation between responses to SARS-CoV-2 (Spike-S1 and Nucleocapsid) and MMR and Tdap vaccine proteins in both SARS-CoV-2 infected individuals and individuals immunized with mRNA-based SARS-CoV-2 vaccines. The overlapping T cell population contained effector memory T cells (TEMRA) previously implicated in anti-viral immunity and their activation required APC-derived IL-15. TCR- and scRNA-sequencing detected cross-reactive clones with TEMRA features among the cells recognizing SARS-CoV-2, MMR and Tdap epitopes. A propensity-weighted analysis of 73,582 COVID-19 patients revealed that severe disease outcomes (hospitalization and transfer to intensive care unit or death) were reduced in MMR or Tdap vaccinated individuals by 38-32% and 23-20% respectively. In summary, SARS-CoV-2 re-activates memory T cells generated by Tdap and MMR vaccines, which may reduce disease severity.
Fabrication and Evaluation of Mechanical and Tribological Properties of ultra-high-molecular-weight polyethylene-based Nanocomposites Reinforced with Hydroxyapatite, Zirconia and Multi-walled Carbon Nanotubes
Authors: Nikbakht Alireza , Javadpour Jafar , Naimi-Jamal M. Reza , Rezaie Hamidreza
Published: May 2021

The unique properties of ultra-high-molecular-weight polyethylene (UHMWPE) have made composites based on this polymer the gold standard choice for articulating surfaces used in arthroplasty. However, wear debris released by prosthesis is still a major concern of the implants. In this study, we address the urgent need to revisit the current methodologies used in designing these biomaterials by fabricating UHMWPE-based nanocomposite with Hydroxyapatite (HA), Multi-walled Carbon Nanotubes (MWCNTs), and Zirconia as additives. We investigated how different combinations of these additives impact the nanocomposites’ hardness, plasticity index (PI), and friction coefficient. Our results show a constant increase in hardness by increasing Zirconia. The MTT assay test and Scanning Electron Microscopy (SEM) demonstrated an increase in cell attachment and cell viability. Examining various additives’ amounts, we can further explore the possibility of reaching an optimum proportion of the ingredients. Compared with other UHMWPE-based nanocomposites (UHMWPE-HA-MWCNT’s), the fabricated nanocomposite shows an improvement in tribological properties.
Minian an Open-source Miniscope Analysis Pipeline
Authors: Dong Zhe , Mau William , Feng Yu , Pennington Zachary T. , Chen Lingxuan , Zaki Yosif , Rajan Kanaka , Shuman Tristan , Aharoni Daniel , Cai Denise J.
Published: May 2021

Miniature microscopes have gained considerable traction forin vivocalcium imaging in freely behaving animals. However, extracting calcium signals from raw videos is a computationally complex problem and remains a bottleneck for many researchers utilizing single-photonin vivocalcium imaging. Despite the existence of many powerful analysis packages designed to detect and extract calcium dynamics, most have either key parameters that are hard-coded or insufficient step-by-step guidance and validations to help the users choose the best parameters. This makes it difficult to know whether the output is reliable and meets the assumptions necessary for proper analysis. Moreover, large memory demand is often a constraint for setting up these pipelines since it limits the choice of hardware to specialized computers. Given these difficulties, there is a need for a low memory demand, user-friendly tool offering interactive visualizations of how altering parameters at each step of the analysis affects data output. Our open-source analysis pipeline, Minian (Miniscope Analysis), facilitates the transparency and accessibility of single-photon calcium imaging analysis, permitting users with little computational experience to extract the location of cells and their corresponding calcium traces and deconvolved neural activities. Minian contains interactive visualization tools for every step of the analysis, as well as detailed documentation and tips on parameter exploration. Furthermore, Minian has relatively small memory demands and can be run on a laptop, making it available to labs that do not have access to specialized computational hardware. Minian has been validated to reliably and robustly extract calcium events across different brain regions and from different cell types. In practice, Minian provides an open-source calcium imaging analysis pipeline with user-friendly interactive visualizations to explore parameters and validate results.
Global Gene Expression Divergence in Spontaneous Mutation Accumulation Lines ofCaenorhabditis elegansunder Varying Efficiency of Selection
Authors: Deiss Thaddeus C. , Konrad Anke , Bergthorsson Ulfar , Katju Vaishali
Published: May 2021

To ascertain the effect of relaxation of selection on global gene expression,Caenorhabditis elegansmutation accumulation (MA) lines were propagated under varying degrees of efficiency of selection determined by their different population sizes (N= 1, 10 and 100). Both the mutational variance (Vm), and the residual variance (Vr) were greatest in MA lines with the lowest efficiency of natural selection. The results suggest that gene expression is under strong balancing selection. Furthermore, mutations resulting in increased transcriptional noise or sensitivity to microenvironmental variation accumulate most under extreme genetic drift. In contrast, theVm/Vrratio was lowest in theN=1 lines. Chromatin domains associated with broad gene silencing and active transcription exhibited the greatest and the smallest increase in transcriptional variation, respectively. Furthermore, the preponderance of overexpressed genes was especially pronounced in mitochondrial respiration, stress response, and immune system pathways, especially in low fitnessN= 1 lines.
High performance single-cell gene regulatory network inference at scale: The Inferelator 3.0
Authors: Gibbs Claudia Skok , Jackson Christopher A , Saldi Giuseppe-Antonio , Tjärnberg Andreas , Shah Aashna , Watters Aaron , De Veaux Nicholas , Tchourine Konstantine , Yi Ren , Hamamsy Tymor , Castro Dayanne M , Carriero Nicholas , Gorissen Bram L , Gresham David , Miraldi Emily R , Bonneau Richard
Published: May 2021

Motivation

Gene regulatory networks define regulatory relationships between transcription factors and target genes within a biological system, and reconstructing them is essential for understanding cellular growth and function. Methods for inferring and reconstructing networks from genomics data have evolved rapidly over the last decade in response to advances in sequencing technology and machine learning. The scale of data collection has increased dramatically; the largest genome-wide gene expression datasets have grown from thousands of measurements to millions of single cells, and new technologies are on the horizon to increase to tens of millions of cells and above.

Results

In this work, we present the Inferelator 3.0, which has been significantly updated to integrate data from distinct cell types to learn context-specific regulatory networks and aggregate them into a shared regulatory network, while retaining the functionality of the previous versions. The Inferelator is able to integrate the largest single-cell datasets and learn cell-type specific gene regulatory networks. Compared to other network inference methods, the Inferelator learns new and informativeSaccharomyces cerevisiaenetworks from single-cell gene expression data, measured by recovery of a known gold standard. We demonstrate its scaling capabilities by learning networks for multiple distinct neuronal and glial cell types in the developingMus musculusbrain at E18 from a large (1.3 million) single-cell gene expression dataset with paired single-cell chromatin accessibility data.

Availability

The inferelator software is available on GitHub (https://github.com/flatironinstitute/inferelator) under the MIT license and has been released as python packages with associated documentation (https://inferelator.readthedocs.io/).
Benefits and Limits of Phasing Alleles for Network Inference of Allopolyploid Complexes
Authors: Tiley George P. , Crowl Andrew A. , Manos Paul S. , Sessa Emily B. , Solís-Lemus Claudia , Yoder Anne D. , Burleigh J. Gordon
Published: May 2021

Accurately reconstructing the reticulate histories of polyploids remains a central challenge for understanding plant evolution. Although phylogenetic networks can provide insights into relationships among polyploid lineages, inferring networks may be hindered by the complexities of homology determination in polyploid taxa. We use simulations to show that phasing alleles from allopolyploid individuals can improve phylogenetic network inference under the multispecies coalescent by obtaining the true network with fewer loci compared to haplotype consensus sequences or sequences with heterozygous bases represented as ambiguity codes. Phased allelic data can also improve divergence time estimates for networks, which is helpful for evaluating allopolyploid speciation hypotheses and proposing mechanisms of speciation. To achieve these outcomes in empirical data, we present a novel pipeline that leverages a recently developed phasing algorithm to reliably phase alleles from polyploids. This pipeline is especially appropriate for target enrichment data, where depth of coverage is typically high enough to phase entire loci. We provide an empirical example in the North AmericanDryopterisfern complex that demonstrates insights from phased data as well as the challenges of network inference. We establish that our pipeline (PATÉ: Phased Alleles from Target Enrichment data) is capable of recovering a high proportion of phased loci from both diploids and polyploids. These data may improve network estimates compared to using haplotype consensus assemblies by accurately inferring the direction of gene flow, but statistical non-identifiability of phylogenetic networks poses a barrier to inferring the evolutionary history of reticulate complexes.
Time to fixation in changing environments
Authors: Kaushik Sachin , Jain Kavita
Published: May 2021

Although a large number of experimental and theoretical studies have been carried out in a constant environment, as natural environments vary in time, it is important to ask if and how these results are affected by a changing environment. Here, we study the properties of the conditional fixation time of a mutant in a finite, randomly mating diploid population which is evolving in a periodically changing environment. In a static environment, as the conditional mean fixation time of a co-dominant beneficial mutant is equal to that of a deleterious mutant with the same magnitude of selection coefficient, similar patterns for beneficial and deleterious sweeps may result. We find that this symmetry breaks even when the environment is changing slowly. Furthermore, for intermediate dominance, the conditional mean fixation time of a beneficial mutant in a slowly changing environment depends weakly on the dominance coefficient and is close to the corresponding results in the static environment; however, the fixation time for a deleterious mutant under moderate selection with a slowly varying selection coefficient differs substantially from that in the constant environment when the mutant is recessive. Our results thus suggest that the variability patterns and levels for beneficial sweeps are mildly affected by temporally varying environment but changing environment is likely to strongly impact those due to recessive deleterious sweeps.
Crystal structure of enoyl-CoA hydratase from Thermus thermophilus HB8
Authors: Padavattan Sivaraman , Jos Sneha , Gogoi Hemanga , Bagautdinov Bagautdin
Published: May 2021

Fatty-acid degradation is an oxidative process that involves four enzymatic steps and is referred to as the β-oxidation pathway. During this process, long-chain acyl-CoAs are broken down into acetyl-CoA, which enters the mitochondrial tricarboxylic acid (TCA) cycle, resulting in the production of energy in the form of ATP. Enoyl-CoA hydratase (ECH) catalyzes the second step of the β-oxidation pathway by the syn addition of water to the double bond between C2 and C3 of a 2-trans-enoyl-CoA, resulting in the formation of a 3-hydroxyacyl CoA. Here, the crystal structure of ECH from Thermus thermophilus HB8 (TtECH) is reported at 2.85 Å resolution. TtECH forms a hexamer as a dimer of trimers, and wide clefts are uniquely formed between the two trimers. Although the overall structure of TtECH is similar to that of a hexameric ECH from Rattus norvegicus (RnECH), there is a significant shift in the positions of the helices and loops around the active-site region, which includes the replacement of a longer α3 helix with a shorter α-helix and 310-helix in RnECH. Additionally, one of the catalytic residues of RnECH, Glu144 (numbering based on the RnECH enzyme), is replaced by a glycine in TtECH, while the other catalytic residue Glu164, as well as Ala98 and Gly141 that stabilize the enolate intermediate, is conserved. Their putative ligand-binding sites and active-site residue compositions are dissimilar.
From corporate social responsibility activities to financial performance: role of innovation and competitive advantage
Authors: Zahid Mahnoor , Naeem Hina , Aftab Iqra , Mughal Sajawal Ali
Published: May 2021

Purpose

The purpose of this study is to scrutinize the effect of corporate social responsibility activities (CSRA) of the firm on its financial performance (FP) and analyze the mediating role of innovation and competitive advantage (CA) in the relationship between CSRA and FP in the manufacturing sector of an emerging country, i.e. Pakistan.

Design/methodology/approach

Data has been collected through an electronic structured questionnaire from 300 middle-level and top-level managers by surveying different manufacturing firms of Gujranwala, Pakistan. The study’s hypotheses have been checked by analyzing the reliability and validity of data and applying confirmatory factor analysis and structural equation modeling through statistical package for the social sciences and analysis of moment structures.

Findings

Outcomes of this study supported the hypothesized model. It has been found that the CSRA plays a significant positive role in determining the FP of the firm. Furthermore, the CA and innovation have been proved as significant mediators between CSRA and FP.

Originality/value

The first time examining the intermediation of innovation and CA in the relationship between CSRA and FP is the primary input of this study to the literature. Practically, this study’s findings will help strategy makers of manufacturing firms in emerging countries develop better strategies for implementing CSRA, enhancing innovation, seeking CA and improving FP.
Numerical modeling for the effects of gravel permeability coefficient based on DEM and CFD method
Authors: Zhang Anan , Yang Jie , Ma Chunhui , Cheng Lin , Hu Liangcai
Published: May 2021

Purpose

The purpose of this paper is to form a numerical simulation method for permeability coefficient that can consider the characteristics of gravel gradation and further explore the effects of indoor test factors and gradation characteristics on the permeability coefficient of gravel.

Design/methodology/approach

The random point method is used to establish the polyhedral gravel particle model, the discrete element method (DEM) is used to construct the gravel permeability test sample with gradation characteristics and the finite element method is used to calculate the permeability coefficient to form a DEM-computational fluid dynamics combined method to simulate the gravel seepage characteristics. Then, verified by the indoor test results. Based on this method, the influence of sample size, treatment method of oversize particles and the content of fine particles on the permeability coefficient of gravel is studied.

Findings

For the gravel containing large particles, the larger size permeameter should be used as far as possible. When the permeameter size is limited, the equal weight substitution method is recommended for the treatment method of oversized particles. Compared with the porosity, the pore connectivity has a higher correlation with the permeability coefficient of the sample.

Research limitations/implications

Insufficient consideration of the movement of gravel particles in the seepage process is also an issue for further study.

Originality/value

The simulation method described in this paper is helpful for qualitative analysis, quantitative expression of pore size and makes up for the defect that the seepage characteristics in pores cannot be observed in laboratory tests.
Personality and eating behavior in a food festival: understanding visitors’ loyalty from the perspective of food-related personality traits
Authors: Hsu Li-Chun
Published: May 2021

Purpose

This study aims to investigate the effects of visitors’ dietary habits on their acceptance of local food from the perspective of positive (e.g. local food involvement) and negative (e.g. food neophobia) food-related personality traits.

Design/methodology/approach

A survey was conducted on visitors to the Slow Food Festival in Taitung, Taiwan. A total of 327 valid questionnaire responses were collected and structural equation modeling was used to conduct path analyzes.

Findings

The analysis results supported all hypotheses. Food neophobia plays a key factor in moderating roles.

Originality/value

This study contributes to the literature by integrating positive and negative perspectives of food-related personality traits. In addition, this study proposes that food neophobia plays a moderating role in food choice and behavioral decisions.
RHCC intervention: strengthening the delivery and coverage of sexual and reproductive health care during floods in Bangladesh
Authors: Ray-Bennett Nibedita Shankar , Corsel Denise Marsha Jeanor , Goswami Nimisha , Bhuiyan Maqbul Hossain
Published: May 2021

Purpose

The quality and availability of sexual and reproductive health care are key determinants to reducing maternal mortalities and morbidities in disaster settings; yet, these services are often lacking in developing countries. Reducing maternal mortality and morbidity is currently the main targets of the UN’s Sustainable Development Goal (SDG) 3. The purpose of this study was to develop an intervention package called RHCC (Reproductive Health Kit 8; Capacity building; Community awareness), and to implement and evaluate it in three primary health-care (PHC) facilities in Belkuchi, Bangladesh, in order to improve the quality and availability of post-abortion care (PAC) during the 2017 floods.

Design/methodology/approach

This research used both quantitative and qualitative methods to develop, implement and assess the RHCC in three flood-prone PHC facilities in Belkuchi.

Findings

The RHCC was implemented during the floods of 2017. The findings pre- and post-intervention suggest it led to an increase in skilled management among health workers, an increase in the quality of care for clients and the availability of PAC at three PHC facilities during floods.

Originality/value

Due to its geographic location, Bangladesh is exposed to recurrent floods and cyclones. Evidence-based integrated intervention packages, such as the RHCC, can improve the quality and availability of reproductive health care during disasters at PHC level and, in doing so, can promote the UN’s agenda on “disaster resilient health system” to achieve the SDG 3, and the WHO’s campaign on universal health coverage.
Management of the COVID-19 epidemic in a French immigration detention center
Authors: Soussy Nicolas , Dufayet Laurène , Ravault Etienne , Viron Sophie , Gorgiard Charlotte , Fournier Lionel
Published: May 2021

Purpose

The purpose of this paper is to give an overview of management of the COVID-19 epidemic in a French immigration detention center.

Design/methodology/approach

During containment in France because of COVID-19, the judicial authorities had to deal with the risk of contamination within immigration detention centers (IDC). In the Paris IDC, which can usually receive up to 240 individuals, measures have been taken to limit the risk of contamination by releasing individuals without prior judicial conviction and testing the others by a nasal swab.

Findings

The test was done for all the present individuals (48), except two who refused. Eight tests (17.4%) were positive and only one was symptomatic. Individuals testing positive for COVID-19 were transferred into COVID-centers specially created during this health crisis.

Originality/value

Management of the COVID-19 epidemic in this French IDC illustrates the necessity of good cooperation between judicial authorities and medical teams in charge of those centers and the difficulty of balancing public health actions with state security.
Mining and exploring electronic word-of-mouth from Twitter: case of the Java Jazz Festival
Authors: Saragih Harriman Samuel
Published: May 2021

Purpose

This paper aims to explore textual patterns in ten years of electronic word-of-mouth communications amongst social media (SM) users of the Java Jazz Festival.

Design/methodology/approach

This study uses a data-scraping technique to gather user-generated content from Twitter. Word-cloud and word-frequency analysis, along with descriptive coding and pattern matching, are used to categorise the initial findings. Trends and differences in terms of the number of tweets over a ten-year period were examined using analysis of variance and seasonality analysis.

Findings

From more than 1.3 million Twitter tweets between 2008 and 2018, this study identified six initial themes. Quantitative analysis revealed that the number of tweets differed significantly in the four quarters of the ten-year period.

Research limitations/implications

The results of this study contrast with the claim that digital media communication generally occurs before a festival begins and are least during the festival. Nevertheless, this study supports the notion that SM interaction results in positive consequences, drives conversations amongst users and increases engagement.

Practical implications

This study offers five practical implications for music festival organisers and related entities.

Originality/value

To the best of the author’s knowledge, this study is the first to provide a systematic and practical data mining and interpretation approach from Twitter within a ten-year period in the Asia Pacific context, through the case of the Java Jazz Festival.
Reforming state budgeting in the vortex of policy conditionality, political instability and technical support flux
Authors: Cohen Sandra , Karatzimas Sotirios
Published: May 2021

Purpose

Greece had to undertake several reforms under intense policy conditionality pressures – stemming from the three financial support programs agreed between the Greek Government and the Troika – and political instability. Within this context, this study aims to analyze the role of politicians and technical assistance staff in the administrative reform of the Greek state budget.

Design/methodology/approach

The study adopts the approach of an extreme country-case study which is analyzed through a theoretical framework with insights from the resource dependency theory and the concept of policy conditionality. The theoretical framework is supported by documents of the International Monetary Fund and the European Commission, including the technical Memoranda of Understanding (MoUs) and their progress reports and is informed by the outcome of interviews with General Accounting Office executives.

Findings

While the budget reform eventually met the MoU requirements, the frequent changes at the government level, the constant renegotiations with the Troika that initiated changes to the plan and the instability of the technical assistance teams formed to support the reform contributed to important implementation delays.

Originality/value

The study contributes to the research agenda on accounting reforms during periods of financial crises by providing evidence on the role of politicians’ level of ownership and technical assistance staff contribution.