bluuebunny/crossref_metadata_2025 huggingface dataset:
Water soluble polysaccharides from Spirulina platensis exhibited cyto/DNA protection and suppress the growth of gastric cancer cells via modulation of galectin-3
Authors: Uppin Vinayak , Dharmesh Shylaja M , Sarada R
Published: December 2021

Polysaccharides from natural sources play a significant role in the management of different cancer types including gastric cancer. In this study, we reported the effect of spirulina polysaccharide (Sp) on galectin-3 modulatory activity on gastric cancer cells. The polysaccharide was isolated from the spirulina biomass, characterized, and the in silico, in vitro studies are carried out to assess the bioactivities. The isolated Sp possessed average molecular weight of 1457 kDa, and galactose (42%) as major sugar along with Rhamnose, Arabinose, Xylose, and Mannose. Further, characterization of Sp by FT-IR and NMR spectrum indicated the presence of (β1-4D) galactose sugar with galactoarabinorhamnoglycan backbone. Among the monosaccharides, galactose showed highest binding affinity with galectin-3 protein as evidenced by the in silico interaction study. The obtained Sp, inhibited the proliferation of AGS gastric cancer cells by 48 % without affecting normal NIH/3T3 cells as opposed to doxorubicin, a known anticancer drug. Also, Sp exhibited galectin-3 mediated haemagglutination inhibition with MIC of 9.37 μg/mL compared to galactose 6.25 μg/mL, sugar specific to galectin-3. The Sp treatment significantly (p<0.05) lowered the expression of galectin-3 by 32 % compared to untreated control cells. In addition, Sp exhibited the potent cytoprotection in RBCs, Buccal cells, and DNA exposed to oxidants. Thus, the findings suggest that the polysaccharide from spirulina offer a promising therapeutic strategy in the management of gastric cancer in addition to its currently known nutritional and pharmaceutical applications.
The probability of joint monophyly of all species in an arbitrary species tree
Authors: Mehta Rohan S. , Steel Mike , Rosenberg Noah A.
Published: December 2021

Monophyly is a feature of a set of genetic lineages in which every lineage in the set is more closely related to all other members of the set than it is to any lineage outside the set. Multiple sets of lineages that are separately monophyletic are said to be reciprocally monophyletic, or jointly monophyletic. The prevalence of reciprocal monophyly, or joint monophyly, has been used to evaluate phylogenetic and phylogeographic hypotheses, as well as to delimit species. These applications often make use of a probability of joint monophyly under models of gene lineage evolution. Studies in coalescent theory have computed this joint monophyly probability for small numbers of separate groups in arbitrary species trees, and for arbitrary numbers of separate groups in trivial species trees. Here, generalizing existing results on monophyly probabilities under the multispecies coalescent, we derive the probability of joint monophyly for arbitrary numbers of separate groups in arbitrary species trees. We illustrate how our result collapses to previously examined cases. We also study the effect of tree height, sample size, and number of species on the probability of joint monophyly. The result also enables computation of relatively simple lower and upper bounds on the joint monophyly probability. Our results expand the scope of joint monophyly calculations beyond small numbers of species, subsuming past formulas that have been used in simpler cases.
Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq
Authors: Replogle Joseph M. , Saunders Reuben A. , Pogson Angela N. , Hussmann Jeffrey A. , Lenail Alexander , Guna Alina , Mascibroda Lauren , Wagner Eric J. , Adelman Karen , Lithwick-Yanai Gila , Iremadze Nika , Oberstrass Florian , Lipson Doron , Bonnar Jessica L. , Jost Marco , Norman Thomas M. , Weissman Jonathan S.
Published: December 2021

A central goal of genetics is to define the relationships between genotypes and phenotypes. High-content phenotypic screens such as Perturb-seq (pooled CRISPR-based screens with single-cell RNA-sequencing readouts) enable massively parallel functional genomic mapping but, to date, have been used at limited scales. Here, we perform genome-scale Perturb-seq targeting all expressed genes with CRISPR interference (CRISPRi) across >2.5 million human cells and present a framework to power biological discovery with the resulting genotype-phenotype map. We use transcriptional phenotypes to predict the function of poorly-characterized genes, uncovering new regulators of ribosome biogenesis (includingCCDC86,ZNF236, andSPATA5L1), transcription (C7orf26), and mitochondrial respiration (TMEM242). In addition to assigning gene function, single-cell transcriptional phenotypes allow for in-depth dissection of complex cellular phenomena – from RNA processing to differentiation. We leverage this ability to systematically identify the genetic drivers and consequences of aneuploidy and to discover an unanticipated layer of stress-specific regulation of the mitochondrial genome. Our information-rich genotype-phenotype map reveals a multidimensional portrait of gene function and cellular behavior.
Auxin-driven ecophysiological diversification of leaves in domesticated tomato
Authors: Moreira Juliene d. R. , Rosa Bruno L. , Lira Bruno S. , Lima Joni E. , Souza Ludmila N. , Otoni Wagner C. , Figueira Antonio , Freschi Luciano , Sakamoto Tetsu , Peres Lázaro E. P. , Rossi Magdalena , Zsögön Agustin
Published: December 2021

Heterobaric leaves have bundle sheath extensions (BSEs) that compartmentalise the parenchyma, whereas homobaric leaves do not. The presence of BSEs affects leaf hydraulics and photosynthetic rate. The tomato (Solanum lycopersicum) obscuravenosa (obv) mutant lacks BSEs. Here we identify the obv gene and the causative mutation, a non-synonymous amino acid change that disrupts a C2H2 zinc finger motif in a putative transcription factor. This mutation exists as a rare polymorphism in the natural range of wild tomatoes, but has increased in frequency in domesticated tomatoes, suggesting that the latter diversified into heterobaric and homobaric leaf types. The obv mutant displays reduced vein density, leaf hydraulic conductance and photosynthetic assimilation rate. We show that these and other effects on plant development, including changes in leaf insertion angle, leaf margin serration, minor vein density and fruit shape, are controlled by OBV via changes in auxin signalling. Loss of function of the transcriptional regulator AUXIN RESPONSE FACTOR (ARF4) also results in defective BSE development, revealing an additional component of a novel genetic module controlling aspects of leaf development important for ecological adaptation and subject to breeding selection.

One sentence summary

distribution of tomato heterobaric and homobaric leaves is controlled by a single-nucleotide polymorphism in an auxin-related transcription factor
ICoRD: Iterative correlation-based ROI detection method for the extraction of neural signals in calcium imaging
Authors: Kang Seongtak , Park Jiho , Kim Kyungsoo , Lim Sung-Ho , Kim Samhwan , Choi Joon Ho , Rah Jong-Cheol , Choi Ji-Woong
Published: December 2021

In vivo calcium imaging is a standard neuroimaging technique that allows selective observation of target neuronal activities. In calcium imaging, neuron activation signals provide key information for the investigation of neural circuits. For efficient extraction of the calcium signals of neurons, selective detection of the region of interest (ROI) pixels corresponding to the active subcellular region of the target neuron is essential. However, current ROI detection methods for calcium imaging data exhibit a relatively low signal extraction performance from neurons with a low signal-to-noise power ratio (SNR). This is problematic because a low SNR is unavoidable in many biological experiments. Therefore, we propose an iterative correlation-based ROI detection (ICoRD) method that robustly extracts the calcium signal of the target neuron from a calcium imaging series with severe noise. ICoRD extracts calcium signals closer to the ground-truth calcium signal than the conventional method from simulated calcium imaging data in all low SNR ranges. Additionally, this study confirmed that ICoRD robustly extracts activation signals against noise, even within in vivo environments. ICoRD showed reliable detection from neurons with a low SNR and sparse activation, which were not detected by conventional methods. ICoRD will facilitate our understanding of neural circuit activity by providing significantly improved ROI detection in noisy images.
Nuclei function as wedges to pry open spaces and promote collective, confined cell migrationin vivo
Authors: Penfield Lauren , Montell Denise J.
Published: December 2021

Cells migrate collectively through confined environments during development and cancer metastasis. The nucleus, a stiff organelle, impedes single cells from squeezing into narrow channels within artificial environments, but how nuclei affect collective cell migration into compact tissuesin vivois unknown. Here, we use border cells in the fly ovary to study nuclear dynamics in collective, confinedin vivomigration. Border cells delaminate from the follicular epithelium and squeeze into tiny spaces between cells called nurse cells. The lead cell nucleus transiently deforms as it extends into the lead cell protrusion, which then widens. The nuclei of follower cells deform less. Depletion of theDrosophilaB-type lamin, Lam, compromises nuclear integrity, hinders expansion of a leading protrusion, and impedes border cell movement. Cortical myosin II accumulates behind the nucleus and moves it into the protrusion in wildtype but not Lam-depleted cells. These data suggest that the nucleus stabilizes lead cell protrusions to help cells wedge open spaces between nurse cells.

DuringDrosophilaborder cell migration, the B-type lamin Lam maintains nuclear envelope integrity, stabilizes the lead cell protrusion, and promotes cluster invasion between nurse cells. The nucleus may function as a wedge to prom collective, confinedin vivomovement.
Caveolae mediated endocytosis of VLDL particles in macrophages requires NPC1 and STARD3 for further lysosomal processing
Authors: Deng Lei , Vrieling Frank , Stienstra Rinke , Hooiveld Guido , Feitsma Anouk L. , Kersten Sander
Published: December 2021

Macrophages accumulate triglycerides under certain pathological conditions such as atherosclerosis. Triglycerides are carried in the bloodstream as part of very low-density lipoproteins (VLDL) and chylomicrons. How macrophages take up and process VLDL-lipids is not very well known. Here, using VLDL-sized triglyceride-rich emulsion particles, we aimed to study the mechanism by which VLDL-triglycerides are taken up, processed, and stored in macrophages. Our results show that macrophage uptake of emulsion particles mimicking VLDL (VLDLm) is dependent on lipoproteins lipase (LPL) and requires the lipoprotein-binding C-terminal domain of LPL but not the catalytic N-terminal domain. Subsequent internalization of VLDLm-triglycerides by macrophages is carried out by caveolae-mediated endocytosis, followed by triglyceride hydrolysis catalyzed by lysosomal acid lipase. Transfer of lysosomal fatty acids to the ER for subsequent storage as triglycerides is mediated by Stard3, whereas NPC1 was found to promote the extracellular efflux of fatty acids from lysosomes. Our data provide novel insights into how macrophages process VLDL-derived triglycerides and suggest that macrophages have the remarkable capacity to excrete part of the internalized triglycerides as fatty acids.
Amino acid substitutions in human growth hormone affect coiled-coil content and receptor binding
Authors: Rajkovic Andrei , Kanchugal Sandesh , Abdurakhmanov Eldar , Howard Rebecca , Gräslund Astrid , Wärmländer Sebastian , Erwin Joseph , Danielson Helena , Flores Samuel
Published: December 2021

The interaction between human Growth Hormone (hGH) and hGH Receptor (hGHR) has great relevance to human diseases such as acromegaly and cancer. HGH has been extensively engineered by other workers to improve binding and other properties. We used a computational screen to select substitutions at single hGH positions within the hGHR-binding site. We find that, while many successfully slow down dissociation of the hGH-hGHR complex once bound, they also slow down the association of hGH to hGHR. We are particularly interested in E174 which belongs to the hGH zinc-binding triad, and which spans coiled-coil helices and obeys the coiled-coil heptad pattern. Surprisingly, substituting E174 with A leads to substantial increase in an experimental measure of coiled-coil content. E174A is known to increase affinity of hGH against hGHR; here we show that this is simply because the off-rate is slowed down more than the on-rate, in line with what has been found for other affinity-improving mutations. For E174Y (and mutations at other sites) the slowdown in on-rate was greater, leading to decreased affinity. The results point to a link between coiled-coiling, zinc binding, and hGHR-binding affinity in hGH, and also suggest rules for choosing affinity-increasing substitutions.
Genomic characteristics of recently recognized Vibrio cholerae El Tor lineages associated with cholera in Bangladesh, 1991-2017
Authors: Monir Md Mamun , Hossain Talal , Morita Masatomo , Ohnishi Makoto , Johura Fatema-Tuz , Sultana Marzia , Monira Shirajum , Ahmed Tahmeed , Thomson Nicholas , Watanabe Haruo , Huq Anwar , Colwell Rita R. , Seed Kimberley , Alam Munirul
Published: December 2021

Comparative genomic analysis of Vibrio cholerae El Tor associated with endemic cholera in Asia revealed two distinct lineages, one dominant in Bangladesh and the other in India. An in depth whole genome study of V. cholerae El Tor clinical strains isolated during endemic cholera in Bangladesh (1991 – 2017) included reference genome sequence data obtained online. Core genome phylogeny established using single nucleotide polymorphisms (SNPs) showed V. cholerae El Tor strains comprised two lineages, BD-1 and BD-2, which, according to Bayesian phylodynamic analysis, originated from paraphyletic group BD-0 around 1981. BD-1 and BD-2 lineages overlapped temporally but were negatively associated as causative agents of cholera 2004-2017. Genome wide association study (GWAS) revealed 140 SNPs and 31 indels, resulting in gene alleles unique to BD-1 and BD-2. Regression analysis of root to tip distance and year of isolation indicated early BD-0 strains at the base, whereas BD-1 and BD-2 subsequently emerged and progressed by accumulating SNPs. Pangenome analysis provided evidence of gene acquisition by both BD-1 and BD-2, of which six crucial proteins of known function were predominant in BD-2. BD-1 and BD-2 diverged and have distinctively different genomic traits, namely heterogeneity in VSP-2, VPI-1, mobile elements, toxin encoding elements, and total gene abundance. In addition, the observed phage-inducible chromosomal island-like element (PLE1), and SXT ICE elements (ICETET) in BD-2 presumably provided a fitness advantage for the lineage to outcompete BD-1 as the etiological agent of the endemic cholera in Bangladesh, with implications for global cholera epidemiology.

Importance

Cholera is a global disease with specific reference to the Bay of Bengal Ganges Delta where Vibrio cholerae O1 El Tor, causative agent of the disease showed two circulating lineages, one dominant in Bangladesh and the other in India. Results of in-depth genomic study of V. cholerae associated with endemic cholera during the past 27 years (1991 – 2017) indicate emergence and succession of the two lineages, BD-1 and BD-2, arising from a common ancestral paraphylatic group, BD-0, comprising the early strains and short-term evolution of the bacterium in Bangladesh. Among the two V. cholerae lineages, BD-2 supersedes BD-1 and is predominant in the most recent endemic cholera in Bangladesh. The BD-2 lineage contained significantly more SNPs and indels, and showed richness in gene abundance, including antimicrobial resistance genes, gene cassettes, and PLE to fight against bacteriophage infection, acquired over time. These findings have important epidemic implications at a global scale.
Risk of SARS-CoV-2 testing, PCR-confirmed infections and COVID-19--related hospital admissions in children and young people: birth cohort study
Authors: Hardelid Pia , Favarato Graziella , Wijlaars Linda , Fenton Lynda , McMenamin Jim , Clemens Tom , Dibben Chris , Milojevic Ai , Macfarlane Alison , Taylor Jonathon , Cunningham Steven , Wood Rachael
Published: December 2021

Background

There have been no population-based studies of SARS-CoV-2 testing, PCR-confirmed infections and COVID-19-related hospital admissions across the full paediatric age range. We examine the epidemiology of SARS-CoV-2 in children and young people (CYP) aged <23 years.

Methods

We used a birth cohort of all children born in Scotland since 1997, constructed via linkage between vital statistics, hospital records and SARS-CoV-2 surveillance data. We calculated risks of tests and PCR-confirmed infections per 1000 CYP-years between August and December 2020, and COVID-19-related hospital admissions per 100,000 CYP-years between February and December 2020. We used Poisson and Cox proportional hazards regression models to determine risk factors.

Results

Among the 1226855 CYP in the cohort, there were 378402 tests, 19005 PCR confirmed infections and 346 admissions, corresponding to rates of 770.8/1000 (95% confidence interval 768.4-773.3), 179.4 (176.9-182.0) and 29.4/100,000 (26.3-32.8) CYP-years respectively. Infants had the highest COVID-19-related admission rates. Chronic conditions, particularly multiple types of conditions, was strongly associated with COVID-19-related admissions across all ages. The hazard ratio for >1 chronic condition type was 12.2 (7.9-18.82) compared to children with no chronic conditions. 89% of admitted children had no chronic conditions recorded.

Conclusions

Infants, and CYP with chronic conditions are at highest risk of admission with COVID-19, however the majority of admitted CYP have no chronic conditions. These results provide evidence to support risk/benefit analyses for paediatric COVID-19 vaccination programmes. Studies examining whether maternal vaccine during pregnancy prevents COVID-19 admissions in infants are urgently needed.

Funding

UK Research and Innovation-Medical Research Council
A dynamic model to estimate evolving risk of major bleeding after percutaneous coronary intervention
Authors: Hurley Nathan C , Desai Nihar , Dhruva Sanket S. , Khera Rohan , Schulz Wade , Huang Chenxi , Curtis Jeptha , Masoudi Frederick , Rumsfeld John , Negahban Sahand , Krumholz Harlan M. , Mortazavi Bobak J.
Published: December 2021

Background

Bleeding is a complication of percutaneous coronary intervention (PCI), leading to significant morbidity, mortality, and cost. Existing risk models produce a single estimate of bleeding risk anchored at a single point in time and do not update estimates as clinical information emerges, despite the dynamic nature of risk.

Objective

We sought to develop models that update estimates of bleeding risk over time, incorporating evolving clinical information, and to demonstrate updated predictive performance.

Methods

Using data available from the National Cardiovascular Data Registry (NCDR) CathPCI, we trained 6 different tree-based machine learning models to estimate the risk of bleeding at key decision points: 1) choice of access site, 2) prescription of medication prior to PCI, and 3) the choice of closure device.

Results

We included 2,868,808 PCIs; 2,314,446 (80.7%) prior to 2014 for training and 554,362 (19.3%) remaining for validation. Discrimination improved from an AUROC of 0.812 (95% Confidence Interval: 0.812-0.812) using only presentation variables to 0.845 (0.845-0.845) using all variables. Among 123,712 patients classified as low risk by the initial model, 14,441 were reclassified as moderate risk (1.4% experienced bleeds), while 723 were reclassified as high risk (12.5% experienced bleeds). Among 160,165 patients classified as high risk by the initial model, 40 were reclassified to low risk (0% experienced bleeds), and 43,265 to moderate risk (2.5% experienced bleeds).

Conclusion

Accounting for the time-varying nature of data and capturing the association between treatment decisions and changes in risk provide up-to-date information that may guide individualized care throughout a hospitalization.

Condensed Abstract

Existing risk models for bleeding with PCI produce a single estimate anchored at a single point in time. We developed models that update estimates of bleeding risk over time, incorporating evolving clinical information, using data available from the National Cardiovascular Data Registry (NCDR) CathPCI. We trained 6 different machine learning models to estimate the risk of bleeding at key decision points, improving discrimination from an AUROC of 0.812 to 0.845, over time. Accounting for the time-varying nature of data and capturing association between treatments and changes in risk provide up-to-date information that may guide individualized care throughout a hospitalization.
Resource Profile: The Regenstrief Institute COVID-19 Research Data Commons (CoRDaCo)
Authors: Allen Katie S. , Zidan Nader , Dey Vishal , Mendonca Eneida A. , Grannis Shaun , Kasturi Suranga , Khan Babar , Zappone Sarah , Haggstrom David , Ruppert Laura , Schleyer Titus , Ning Xia , Embi Peter , Tachinardi Umberto
Published: December 2021

The primary objective of the COVID-19 Research Data Commons (CoRDaCo) is to provide broad and efficient access to a large corpus of clinical data related to COVID-19 in Indiana, facilitating research and discovery. This curated collection of data elements provides information on a significant portion of COVID-19 positive patients in the State from the beginning of the pandemic, as well as two years of health information prior its onset. CoRDaCo combines data from multiple sources, including clinical data from a large, regional health information exchange, clinical data repositories of two health systems, and state laboratory reporting and vital records, as well as geographic-based social variables. Clinical data cover information such as healthcare encounters, vital measurements, laboratory orders and results, medications, diagnoses, the Charlson Comorbidity Index and Pediatric Early Warning Score, COVID-19 vaccinations, mechanical ventilation, restraint use, intensive care unit and ICU and hospital lengths of stay, and mortality. Interested researchers can visit ridata.org or email askrds@regenstrief.org to discuss access to CoRDaCo.

Key Features

CoRDaCo includes patient-level data on diagnosis and treatment, healthcare utilization, outcomes, and demographics. The level of detail available for each patient varies depending on the source of the clinical data.

CoRDaCo uses geographic identifiers to link patient-specific data to area-level social factors, such as census variables and social deprivation indices.

As of 4/30/21, the CoRDaCo cohort consists of over 776,000 cases, including granular data on over 15,000 patients who were admitted to an intensive care unit, and over 1,362,000 COVID-19-negative controls. Data is currently refreshed two times per month.

The most prevalent comorbidities in the data set include hypertension, diabetes, chronic pulmonary disease, renal disease, cancer, and congestive heart failure.
Syndromic Surveillance-Based Estimates of Vaccine Efficacy Against COVID-Like Illness from Emerging Omicron and COVID-19 Variants
Authors: Varrelman Tanner J. , Rader Benjamin , Astley Christina M. , Brownstein John S.
Published: December 2021

New infections from the omicron variant of SARS-CoV-2 have been increasing dramatically in South Africa since first identification in November 2021. Despite increasing uptake of COVID-19 vaccine, there are concerns vaccine protection against omicron may be reduced compared to other variants. We sought to characterize a surrogate measure of vaccine efficacy in Gauteng, South Africa by leveraging real-time syndromic surveillance data. The University of Maryland Global COVID Trends and Impact Survey (UMD-CTIS) is an online, cross-sectional survey conducted among users sampled from the Facebook active user base. We derived three COVID-like illness (CLI) definitions (stringent, classic, and broad) using combinations of self-reported symptoms (present or not in the prior 24 hours) that broadly tracked with reported COVID-19 cases during June 18, 2021 - December 14, 2021 (inclusive of the delta wave and up-trend of the omicron wave). We used syndromic-surveillance-based CLI prevalence measures among the vaccinated (PV) and unvaccinated (PU) respondents to estimate V ECLIP = 1 - (PV /PU), a proxy for vaccine efficacy, during the delta (June 18-July 18, N= 9,387 surveys) and omicron (December 4-14, N= 2,389 surveys) wave periods. We assume no waning immunity, CLI prevalence approximates incident infection with each variant, and vaccinated and unvaccinated survey respondents in the two variant wave periods are exchangeable. The vaccine appears to have consistently lower V ECLIP against omicron, compared to delta, regardless of the CLI definition used. Stringent CLI (i.e. anosmia plus fever, cough and/or myalgias) yielded a delta V ECLIP = 0.85 [0.54, 0.95] higher than omicron V ECLIP = 0.62 [0.46, 0.72]. Classic CLI (cough plus anosmia, fever, and/or myalgias) gave lower estimates (delta V ECLIP = 0.76 [0.54, 0.87], omicron V ECLIP = 0.51 [0.42, 0.59]), but omicron was still lower than delta. We acknowledge the potential for measurement, confounding, and selection bias, as well as limitations for generalizability for these self-reported, syndromic surveillance-based V ECLIP measures. Thus V ECLIP as estimates of true, population-level vaccine efficacy should therefore be taken with caution. Nevertheless, these preliminary findings demonstrating declining V ECLIP raise concern for a true decline in vaccine efficacy versus waning immunity as a potential contributor to the omicron variant taking hold in Gauteng and elsewhere.
Antibody Responses to 3rd Dose mRNA Vaccines in Nursing Home and Assisted Living Residents
Authors: Zhang Ali , Breznik Jessica A. , Clare Rumi , Nazy Ishac , Miller Matthew S. , Bowdish Dawn M. E. , Costa Andrew P.
Published: December 2021

A comparison of SARS-CoV-2 wild-type and the beta variant virus neutralization capacity between 2 and 3 mRNA vaccine series in nursing home residents, and between nursing home and assisted living residents strongly supports 3rd dose vaccine recommendations, and equivalent polices for nursing homes and assisted living settings. Findings suggest that residents mount a robust humoral response to a 3rd mRNA vaccination, and have greater neuralization capacity compared to a 2 dose series.
Fully Automatic Cell Segmentation with Fourier Descriptors
Authors: Hirling Dominik , Horvath Peter
Published: December 2021

Cell segmentation is a fundamental problem in biology for which convolutional neural networks yield the best results nowadays. In this paper, we present FourierDist, a network, which is a modification of the popular StarDist and SplineDist architectures. While StarDist and SplineDist describe an object by the lengths of equiangular rays and control points respectively, our network utilizes Fourier descriptors, predicting a coefficient vector for every pixel on the image, which implicitly define the resulting segmentation. We evaluate our model on three different datasets, and show that Fourier descriptors can achieve a high level of accuracy with a small number of coefficients. FourierDist is also capable of accurately segmenting objects that are not star-shaped, a case where StarDist performs suboptimally according to our experiments.
The aphid BCR4 structure and activity uncover a new defensin peptide superfamily
Authors: Loth Karine , Parisot Nicolas , Paquet Françoise , Sivignon Catherine , Rahioui Isabelle , Lopes Mélanie Ribeiro , Gaget Karen , Duport Gabrielle , Delmas Agnès F. , Aucagne Vincent , Heddi Abdelaziz , Calevro Federica , da Silva Pedro
Published: December 2021

Aphids (Hemiptera: Aphidoidea) are among the most injuring insects for agricultural plants and their management is a great challenge in agronomical research. A new class of proteins, called Bacteriocyte-specific Cysteine-Rich (BCR), provides an alternative to chemical insecticides for pest control. BCRs have been initially identified in the pea aphid Acyrthosiphon pisum. They are small disulfide bond-rich proteins expressed exclusively in aphid bacteriocytes, the insect derived cells that host intracellular symbiotic bacteria. Here, we show that one out of the A. pisum BCRs, BCR4, displays an outstanding insecticidal activity against the pea aphid, impairing insect survival and nymphal growth, providing evidence for its potential use as a new biopesticides. Our comparative genomics and phylogenetic analysis indicate that BCRs seem restricted to the aphid lineage. The 3D structure of the BCR4 reveals that this peptide belongs to a yet unknown structural class of peptides and defines a new superfamily of defensins.
Sibling rivalry among the ZBTB transcription factor family: homo vs. heterodimers
Authors: Piepoli Sofia , Nogay Liyne , Akkose Umit , Barakat Sarah , Taskiran Hakan , Tolay Nazife , Gezen Melike , Adebali Ogun , Atilgan Canan , Erman Batu
Published: December 2021

The BTB domain is an oligomerization domain found in over 200 proteins encoded in the human genome. In the family of BTB domain and Zinc Finger-containing (ZBTB) transcription factors, 49 members share the same protein architecture. The N-terminal BTB domain is structurally conserved among the family members and serves as the dimerization site while the C-terminal zinc finger motifs mediate DNA binding. The available BTB domain structures from this family reveal a natural inclination for homodimerization. In this study we investigated the potential for heterodimer formation in the cellular environment. We selected five BTB homodimers and four heterodimer structures. We performed in vitro binding assays with fluorescent protein-BTB domain fusions to assess dimer formation. We tested the binding of several BTB pairs, and we were able to confirm the heterodimeric physical interaction between the BTB domains of PATZ1 and PATZ2, previously reported only in an interactome mapping experiment. We also found this pair to be co-expressed in several immune system cell types. Finally, we used the available structures of BTB domain dimers and newly constructed models in extended molecular dynamics simulations (500 ns) to understand the energetic determinants of homo and heterodimer formation. We conclude that heterodimer formation, although frequently described as less preferred than homodimers, is a possible mechanism to increase the combinatorial specificity of this transcription factor family.
Drosophila hemocytes recognize lymph gland tumors of mxc mutants and activate the Toll pathway in reactive oxygen species-dependent manner
Authors: Kinoshita Suzuko , Takarada Kazuki , Inoue Yoshihiro H.
Published: December 2021

Mechanisms of cancer cell recognition and elimination by the innate immune system remains unclear. Circulating hemocytes are associated with the hematopoietic tumors in Drosophila mxcmbn1 mutant larvae. The innate immune signalling pathways are activated in the fat body to suppress the tumor growth by inducing antimicrobial peptides (AMP). Here, we investigated the regulatory mechanism underlying the activation in the mutant. Reactive oxygen species accumulated in the hemocytes due to induction of dual oxidase and its activator. The hemocytes were also localized on the fat body. These were essential for transmitting the information on tumors toward the fat body to induce AMP expression. Regarding to the tumor recognition, we found that matrix metalloproteinase 1 (MMP1) and MMP2 were highly expressed in the tumors. Ectopic expression of MMP2 was associated with AMP induction in the mutants. Furthermore, the basement membrane components in the tumors were reduced and ultimately lost. The hemocytes may recognize the disassembly in the tumors. Our findings highlight the underlying mechanism via which macrophage-like hemocytes recognize tumor cells and relay the information toward the fat body to induce AMPs. and contribute to uncover the immune system’s roles against cancer.

SUMMARY STATEMENT

Drosophila blood cells transmit information regarding the existence of tumor cells to the fat body and induce the production of anti-tumor peptides via the generation of reactive oxygen species.
Genome Assemblies of the Warthog and Kenyan Domestic Pig Provide Insights into Suidae Evolution and Candidate Genes for African Swine Fever Tolerance
Authors: Feng Wen , Zhou Lei , Zhao Pengju , Du Heng , Diao Chenguang , Zhang Yu , Liu Zhen , Jin Wenjiao , Yu Jian , Han Jianlin , Okoth Edward , Morode Raphael , Liu Jian-Feng
Published: December 2021

As warthog (Phacochoerus africanus) has innate immunity against African swine fever (ASF), it is critical to understand the evolutionary novelty of warthog to explain its specific ASF resistance. Here, we present two completed new genomes of one warthog and one Kenyan domestic pig, as the fundamental genomic references to decode the genetic mechanism on ASF tolerance. Our results indicated, multiple genomic variations, including gene losses, independent contraction and expansion of specific gene families, likely moulded warthog’s genome to adapt the environment. Importantly, the analysis of the presence and absence of genomic sequences revealed that, the warthog genome had a DNA sequence absence of the lactate dehydrogenase B (LDHB) gene on chromosome 2 compared to the reference genome. The overexpression and siRNA of LDHB indicated that its inhibition on the replication of ASFV. Combining with large-scale sequencing data of 123 pigs from all over the world, contraction and expansion of TRIM genes families revealed that TRIM family genes in the warthog genome were potentially responsible for its tolerance to ASF. Our results will help further improve the understanding of genetic resistance ASF in pigs.
CONGA: Copy number variation genotyping in ancient genomes and low-coverage sequencing data
Authors: Söylev Arda , Çokoglu Sevim Seda , Koptekin Dilek , Alkan Can , Somel Mehmet
Published: December 2021

Abstract

To date, ancient genome analyses have been largely confined to the study of single nucleotide polymorphisms (SNPs). Copy number variants (CNVs) are a major contributor of disease and of evolutionary adaptation, but identifying CNVs in ancient shotgun-sequenced genomes is hampered by typical low coverage (<1 ×) and short fragments (<80 bps), precluding standard CNV detection software to be effectively applied to ancient genomes. Here we present CONGA, tailored for genotyping CNVs at low coverage. Simulations and down-sampling experiments suggest that CONGA can genotype deletions >1 kbps with F-scores >0.75 at ≥1×, and distinguish between heterozygous and homozygous states. We applied CONGA to genotype 10,002 outgroup-ascertained deletions across a heterogenous set of 71 ancient human genomes spanning the last 50,000 years, produced using variable experimental protocols. A fraction of these (21/71) display divergent deletion profiles unrelated to their population origin, but attributable to technical factors such as coverage and read length. The majority of the sample (50/71), despite originating from nine different laboratories and having coverages 0.44×-26× (median 4×) and read lengths 52-121 bp (median 69), exhibit coherent deletion frequencies. Across these 50 genomes, inter-individual genetic diversity measured using SNPs and CONGA-genotyped deletions are strongly correlated. CONGA-genotyped deletions also display purifying selection signatures, as expected. CONGA thus paves the way for systematic CNV analyses in ancient genomes, despite the technical challenges posed by low and variable genome coverage.
Kismet/CHD7/CHD8 affects gut biomechanics, the gut microbiome, and gut-brain axis in Drosophila melanogaster
Authors: Niosi Angelo , Võ Nguyên Henry , Sundar Punithavathi , Welch Chloe , Penn Aliyah , Yuldasheva Yelena , Alfareh Adam , Rausch Kaitlin , Rukhsar Takhmina , Cavanaugh Jeffery , Yadav Prince , Peterson Stephanie , Brown Raina , Hu Alain , Ardon-Castro Any , Nguyen Darren , Crawford Robert , Lee Wendy , Jensen Mikkel Herholdt , Morris Eliza J. , Mulligan Kimberly
Published: December 2021

The gut-brain axis may contribute to the pathophysiology of neurodevelopmental disorders, yet it is often unclear how risk genes associated with these disorders affect gut physiology in a manner that could impact microbial colonization. We addressed this question using Drosophila melanogaster with a null mutation in kismet, the ortholog of chromodomain helicase DNA-binding protein (CHD) family members CHD7 and CHD8. In humans, CHD7 and CHD8 are risk genes for neurodevelopmental disorders with co-occurring gastrointestinal symptoms. We found kismet mutant flies have a significant increase in gastrointestinal transit time, indicating functional homology of kismet with CHD7/CHD8 in vertebrates. To measure gut tissue mechanics, we used a high-precision force transducer and length controller, capable of measuring forces to micro-Newton precision, which revealed significant changes in the mechanics of kismet mutant guts, in terms of elasticity, strain stiffening, and tensile strength.
Using 16S rRNA metagenomic sequencing, we also found kismet mutants have reduced diversity of gut microbiota at every taxonomic level and an increase in pathogenic taxa. To investigate the connection between the gut microbiome and behavior, we depleted gut microbiota in kismet mutant and control flies and measured courtship behavior. Depletion of gut microbiota rescued courtship defects of kismet mutant flies, indicating a connection between gut microbiota and behavior. In striking contrast, depletion of gut microbiome in the control strain reduced courtship activity. This result demonstrated that antibiotic treatment can have differential impacts on behavior that may depend on the status of microbial dysbiosis in the gut prior to depletion. We propose that Kismet influences multiple gastrointestinal phenotypes that contribute to the gut-brain axis to influence behavior. Based on our results, we also suggest that gut tissue mechanics should be considered as an element in the gut-brain communication loop, both influenced by and potentially influencing the gut microbiome and neuronal development.
Evolution of cities in Borneo: a kaleidoscope of urban landscapes for planning future resilient cities
Authors: Kozlowski Marek , Ibrahim Rahinah , Zaini Khairul Hazmi
Published: December 2021

Purpose

This study aims to examine the trajectory of the urban growth of Borneo by portraying its resilient settlements in the pre-colonial times, tropical sensitive colonial architecture, the built environment of the post–independence period and finally the contemporary city image. This is followed by a comparative study of its major urban centres and determining how globalisation and neoliberalism impact the traditional urban settlements of this island and poses a threat to its rich biodiversity.

Design/methodology/approach

This study uses case study research methodology involving selected cities on the Island of Borneo including Kota Kinabalu, Sandakan, Miri and Kuching (Sabah and Sarawak, Malaysia), Bandar Seri Begawan (Brunei), and major cities of the state of Kalimantan, Indonesia. Data collection includes a literature review, content analysis, field assessment and observations. The major research objectives would address past and current issues in the selected urban environment of Borneo. They address the historical evolution of major cities of Borneo, current urban development trends, the deterioration of the traditional urban fabric as a result of post–independence development and later globalisation.

Findings

This study found that the rich cultural tradition and climate-responsive architecture from the past have been discontinued to pave way for fast track and often speculative development. The results contribute in the convergence of existing shortcomings of cities from three nations on Borneo Island in guiding future sustainable urban planning agenda for achieving a resilient city status while reinstating the character and the sense of place. The study expects the recommendations to become prerequisites for future urban planning in sensitive tropical regions.

Originality/value

This research identified a new “Borneo approach” to urban development. The study strongly recommends top priorities for the central, state and local governments of Malaysia, Brunei and Indonesia allowing the planners and decision-makers to establish a new tropical urban planning initiative with the ample design practice for this unique region in Southeast Asia. The results of this study can serve as the guiding principles for other urban environments in fragile and sensitive tropical regions.
Effect of banana peel flour on rheological, physico-chemical, mineral content and sensory properties of chicken patties
Authors: Chappalwar Anita M. , Pathak Vikas , Goswami Meena , Verma Arun Kumar , Rajkumar V. , Singh Prashant
Published: December 2021

Purpose

The present study was conducted to evaluate the effect of banana peel flour as fat replacer on rheological, physico-chemical, textural, mineral content and sensory properties of chicken patties.

Design/methodology/approach

Ultra low fat chicken patties were prepared with incorporation of banana peel flour at 0% (C), 1% (BP1), 2% (BP2) and 3% (BP3) levels separately to replace 50% externally added vegetable fat in formulation and evaluated for various quality characteristics and sensory attributes.

Findings

Highest G' and G''? modulus were observed in banana peel powder incorporated emulsion. No cross-point was observed at all ranges of frequency in meat emulsions prepared with banana peel. Among physico-chemical properties, control had significantly (p < 0.05) higher emulsion pH, emulsion stability, product pH, water activity values, fat and cholesterol content; however, cooking yield, moisture and ash content, fat retention and moisture retention values increased significantly (p < 0.05) in treatment patties. Mineral, textural and colour parameters had a significant (p < 0.05) effect except on manganese content and a* values. Various sensory scores decreased significantly (p < 0.05) with increased level of banana peel flour.

Practical implications

Sensory scores of 3% banana peel powder incorporated patties were significantly (p < 0.05) lower than other treatments. There was no significant difference between 1 and 2% banana peel incorporated chicken patties. Therefore, an ultra low fat chicken patties incorporated with 2.0% banana peel flour to replace 50% vegetable fat were selected as the best treatment.

Originality/value

Present global trend and life style are currently driving ready-to-eat healthy meat products and factors include extended working hours, increasing number of single-person households and perception of food as reward. Fat is an important component of meat products and imparts tenderness, improving flavor and mouth feel to processed meat products, like chicken patties. However intake of excess energy in form of saturated and unsaturated fat may lead to various life style diseases in consumers. Hence development of ultra low fat chicken patties with incorporation of fruit waste without adverse effect on sensory properties may be a significant challenge.
Good soldier syndrome. Do organizational cynicism and work alienation matter?
Authors: Singh Sabia , Randhawa Gurpreet
Published: December 2021

Purpose

The purpose of this study is to examine the impact of organizational cynicism (OCyn) on organizational citizenship behavior (OCB) among bank employees with a focus on the role of work alienation (WA) as a potential mediator.

Design/methodology/approach

Using standardized questionnaire, data were collected from 381 employees working in the banking sector of Punjab, a northern state of India. Statistical techniques such as hierarchical multiple regression and confirmatory factor analysis along with PROCESS macro were used for data analysis.

Findings

Results reveal that OCyn has a significant negative effect on OCB. Further, WA is found to be significantly partially mediating the relationship between the aforementioned constructs.

Research limitations/implications

This study pertains to a single sector i.e., banking sector restricting the generalizability to other industrial and vocational settings. Further, it may be difficult to draw any causal inferences as the research design adopted for this study is cross-sectional in nature.

Practical implications

In order to promote OCBs among bank employees, the formation of negative workplace attitudes such as OCyn and WA needs to be regulated. This can be achieved through improving communications network, encouraging participative decision-making activities, conducting psychological counseling and stress management training sessions.

Originality/value

This study is one of the scarce empirical research works that have substantiated the direct impact along with the indirect impact of OCyn (through work alienation) on OCB among bank employees.
A matter of others' money: How cash holdings of other firms affect a firm’s cash holding?
Authors: Jinkrawee Jisaba , Lonkani Ravi , Suwanaphan Suchanphin
Published: December 2021

Purpose

This study examines the effects of comparable companies, within the same industry, on cash-holding (CH) levels of a specific firm in the Stock Exchange of Thailand (SET). Peer effects are hypothesized to affect a firm's average CH levels.

Design/methodology/approach

The authors use data of listed firms in the Thai stock markets from 1995 to 2018. The sample consists of 5,277 firm-year observations. The authors perform robustness tests by incorporating gross domestic product, economy and competitiveness.

Findings

Peer firms' CH levels correspond positively to the specific firm's CH. This strengthens further for firms with high cash flow volatility during periods of high competition. Unfavorable economic periods also motivate the association between a firm's CH and peer firms' CH.

Practical implications

A policy on CH should account for cash held by peer firms. Firms can justify their CH policy as compatible with peers' cash flows, especially during periods of competitiveness and an unfavorable economy.

Originality/value

The authors provide novel evidence on how emerging markets' CH levels differ from those in developed markets and propose adjusted explanations for the rivalry- and information-based theories. The findings add substantial knowledge to corporate finance by arguing that CH policies are based on peer firms' strategic moves.