bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunogenicity and safety of a heterologous prime-boost COVID-19 vaccine schedule: ChAdOx1 vaccine Covishield followed by BBV152 Covaxin
Authors: Kant Rajni , Dwivedi Gaurav , Zaman Kamran , Sahay Rima R , Sapkal Gajanan , Kaushal Himanshu , Nyayanit Dimpal A , Yadav Pragya D , Deshpande Gururaj , Singh Rajeev , Chaowdhary Sandeep , Gupta Nivedita , Kumar Sanjay , Abraham Priya , Panda Samiran , Bhargava Balram
Published: October 2021

The evidence for effectiveness of heterologous priming of COVID-19 vaccine is very limited. Here, we studied eighteen participants who received heterologous vaccination regimen of AstraZeneca’s ChAdOx1-nCov-19 followed by inactivated whole virion BBV152. Heterologous group participant doesn’t report any adverse event following immunization and demonstrated high humoral and neutralizing antibody response.
The IUPHAR/BPS guide to PHARMACOLOGY in 2022: curating pharmacology for COVID-19, malaria and antibacterials
Authors: Harding Simon D , Armstrong Jane F , Faccenda Elena , Southan Christopher , Alexander Stephen P H , Davenport Anthony P , Pawson Adam J , Spedding Michael , Davies Jamie A ,   NC-IUPHAR
Published: October 2021

The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb; www.guidetopharmacology.org) is an open-access, expert-curated database of molecular interactions between ligands and their targets. We describe expansion in content over nine database releases made during the last two years, which has focussed on three main areas of infection. The COVID-19 pandemic continues to have a major impact on health worldwide. GtoPdb has sought to support the wider research community to understand the pharmacology of emerging drug targets for SARS-CoV-2 as well as potential targets in the host to block viral entry and reduce the adverse effects of infection in patients with COVID-19. We describe how the database rapidly evolved to include a new family of Coronavirus proteins. Malaria remains a global threat to half the population of the world. Our database content continues to be enhanced through our collaboration with Medicines for Malaria Venture (MMV) on the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY (www.guidetomalariapharmacology.org). Antibiotic resistance is also a growing threat to global health. In response, we have extended our coverage of antibacterials in partnership with AntibioticDB.
dbPTM in 2022: an updated database for exploring regulatory networks and functional associations of protein post-translational modifications
Authors: Li Zhongyan , Li Shangfu , Luo Mengqi , Jhong Jhih-Hua , Li Wenshuo , Yao Lantian , Pang Yuxuan , Wang Zhuo , Wang Rulan , Ma Renfei , Yu Jinhan , Huang Yuqi , Zhu Xiaoning , Cheng Qifan , Feng Hexiang , Zhang Jiahong , Wang Chunxuan , Hsu Justin Bo-Kai , Chang Wen-Chi , Wei Feng-Xiang , Huang Hsien-Da , Lee Tzong-Yi
Published: October 2021

Protein post-translational modifications (PTMs) play an important role in different cellular processes. In view of the importance of PTMs in cellular functions and the massive data accumulated by the rapid development of mass spectrometry (MS)-based proteomics, this paper presents an update of dbPTM with over 2 777 000 PTM substrate sites obtained from existing databases and manual curation of literature, of which more than 2 235 000 entries are experimentally verified. This update has manually curated over 42 new modification types that were not included in the previous version. Due to the increasing number of studies on the mechanism of PTMs in the past few years, a great deal of upstream regulatory proteins of PTM substrate sites have been revealed. The updated dbPTM thus collates regulatory information from databases and literature, and merges them into a protein-protein interaction network. To enhance the understanding of the association between PTMs and molecular functions/cellular processes, the functional annotations of PTMs are curated and integrated into the database. In addition, the existing PTM-related resources, including annotation databases and prediction tools are also renewed. Overall, in this update, we would like to provide users with the most abundant data and comprehensive annotations on PTMs of proteins. The updated dbPTM is now freely accessible at https://awi.cuhk.edu.cn/dbPTM/.
A Tale of Two Regions: An Analysis of Two Decades of Belgian Public Opinion
Authors: Hooghe Marc , Stiers Dieter
Published: October 2021

It has been assumed that a trend toward devolution within a federal country would be associated with a growing apart of public opinion, and the federal kingdom of Belgium is routinely cited as an obvious example in this regard. Since the publication of the seminal Billiet et al. article, more competences have been devolved toward the autonomous regions, and in this research note we update the expectation that this has led to a further growing apart of public opinion in the country. Based on both electoral studies (2009/2014/2019), and the European Social Survey (2002–2018) we investigate whether these institutional differences are associated with a growing apart of public opinion in the regions of Belgium. Our results suggest that while there are clear attitudinal differences between the two major groups in the country, these differences are stable throughout the three-decade observation period. Differences are becoming more outspoken, however, with regard to the preferred extent of federalism. Interestingly, however, the dynamics in public opinion in this regard do not follow the same pattern as electoral results would suggest.
Postoperative Evaluation and Management of Portomesenteric Venous Thrombosis in Patients With IBD
Authors: Patel Maitri , Hedrick Traci
Published: October 2021

CASE SUMMARY:

A 22-year-old woman with medically refractory ulcerative pancolitis underwent laparoscopic total proctocolectomy with IPAA and diverting ileostomy. She was discharged on postoperative day 4 feeling well. Because of the lack of risk factors for venous thromboembolism (including no family history or use of oral contraceptives), she was not discharged with prophylactic low-molecular-weight heparin, but she received low-molecular-weight heparin while in the hospital. The following day, she developed abdominal pain, nausea/vomiting, and decreased ostomy output. An abdominopelvic CT scan demonstrated a small amount of intraperitoneal free air felt to be postoperative in nature, small-bowel dilation consistent with ileus, and extensive portal and superior mesenteric vein thrombosis. She was started on low-molecular-weight heparin that resulted in rapid improvement. A subsequent repeat CT scan a few days later showed decreased clot burden.
Utility of bedside ultrasound derived hepatic and renal parenchymal flow patterns to guide management of acute kidney injury
Authors: Jury David , Shaw Andrew D.
Published: October 2021

Purpose of review

Ideal fluid management of critically ill patients is maintaining an adequate perfusion pressure but avoiding venous congestion. Venous excess ultrasound score (VExUS) quantifies venous congestion to guide the management of fluid balance.

Recent findings

VExUS of abdominal veins measures fluid tolerance and helps clinicians avoid congestion. VExUS scoring predicts the development of acute kidney injury (AKI) that is a common hospital problem resulting in higher mortality and morbidity. VExUS can predict patients at risk of developing AKI post cardiac surgery. VExUS has been associated with an increase in adverse outcomes in a general intensive care population. Hepatic vein ultrasound can manifest as a sequela of right heart failure and pulmonary hypertension. Intrarenal congestion suggests poorer prognosis in heart failure patients. VExUS score has been used in decision-making to remove fluid in patients with cardiorenal syndrome. VExUS scoring may help curtail overly aggressive fluid resuscitation for patients with septic shock and help avoid iatrogenic ‘salt water drowning’

We summarize the technique and clinical practice of VExUS to help guide fluid balance across different populations of critically ill patients.
Faecal microbiota replacement to eradicate antimicrobial resistant bacteria in the intestinal tract – a systematic review
Authors: Bilsen Manu P. , Lambregts Merel M.C. , van Prehn Joffrey , Kuijper Ed J.
Published: October 2021

Purpose of review

Antimicrobial resistance is a rising threat to global health and is associated with increased mortality. Intestinal colonisation with multidrug-resistant organisms (MDRO) can precede invasive infection and facilitates spread within communities and hospitals. Novel decolonisation strategies, such as faecal microbiota transplantation (FMT), are being explored. The purpose of this review is to provide an update on how the field of FMT for MDRO decolonisation has developed during the past year and to assess the efficacy of FMT for intestinal MDRO decolonisation.

Recent findings

Since 2020, seven highly heterogenous, small, nonrandomised cohort studies and five case reports have been published. In line with previous literature, decolonisation rates ranged from 20 to 90% between studies and were slightly higher for carbapenem-resistantEnterobacteriaceaethan vancomycin-resistantEnterococcus. Despite moderate decolonisation rates in two studies, a reduction in MDRO bloodstream and urinary tract infections was observed.

Summary and implications

Although a number of smaller cohort studies show some effect of FMT for MDRO decolonisation, questions remain regarding the true efficacy of FMT (taking spontaneous decolonisation into account), the optimal route of administration, the role of antibiotics pre and post-FMT and the efficacy in different patient populations. The observed decrease in MDRO infections post-FMT warrants further research.
Surgical Versus Nonsurgical Lower Face Contouring: Layperson Perceptions of Attractiveness and Personality Traits
Authors: Chen Jonlin , Abousy Mya , Chow Amanda , Girard Alisa , Jenny Hillary , Choi Jong-Woo , Yang Robin
Published: October 2021

Background:

Traditional approaches to lower face contouring involve ostectomy of the mandibular angle or body. More recently, nonsurgical techniques have gained popularity, including neurotoxin injection to the masseter muscle. This study aims to evaluate layperson perceptions of patient attractiveness and personality traits following lower face contouring using either surgical or nonsurgical treatment.

Methods:

In this survey study distributed via Amazon's Mechanical Turk, respondents viewed a series of 14 patient images obtained in clinic before and after surgical or nonsurgical jawline slimming, or without any facial aesthetic procedure. Respondents rated changes in attractiveness and personality trait scores between the before and after image (score: −50 to 50, with 50 representing the greatest posttreatment increase and 0 representing no change). We used descriptive statistics and multivariable regression to determine differences in respondent ratings between patient images.

Results:

A total of 415 respondents (mean age 38 years, 50.6% female) successfully completed the survey. Compared to patients who underwent nonsurgical treatment, those who received surgery had significantly greater increases in perceived attractiveness (P < 0.001), femininity (P < 0.001), friendliness (P < 0.001), intelligence (P < 0.001), trustworthiness (P < 0.001), financial wealthiness (P < 0.001), dominance (P < 0.01), and self-esteem (P < 0.001). Gonial angles increased and jaw widths decreased following both surgical and nonsurgical intervention, with no statistically significant difference between treatment groups.

Conclusions:

From the layperson perspective, surgical compared to nonsurgical jawline contouring offers greater improvements in perceptions of attractiveness and favorable personality traits.
Defence by demolition? Preserving and relocating the cloister of Segovia cathedral
Authors: Beltrami Costanza
Published: October 2021

In 1520, Segovia's rebel city council besieged the impregnable royal fortress located on a narrow stone outcrop at the far west of the city. The cathedral stood just in front of the fortress, and the rebels demolished part of the church's structure to use it as a secure stronghold. Beyond the physical damage, the revolt demonstrated the peril posed by the proximity of cathedral and castle. Unsurprisingly, it was soon decided that the cathedral would be relocated to the city's main square. Deserted by its canons and chaplains, the old church was a ruin by 1562, while its younger counterpart was slowly reaching completion. Neglect coexisted with preservation: the first step in the construction of a new cathedral was the decision to move the building's cloister—stone by stone—from the old to the new site. This paper discusses the relocation, exploring its denouement and contextualizing it within pre-modern perspectives on heritage and architecture.
Heavy metal pollution and the role of inorganic nanomaterials in environmental remediation
Authors: Mensah Michael B. , Lewis David J. , Boadi Nathaniel O. , Awudza Johannes A. M.
Published: October 2021

Contamination of water and soil with toxic heavy metals is a major threat to human health. Although extensive work has been performed on reporting heavy metal pollutions globally, there are limited review articles on addressing this pernicious phenomenon. This paper reviews inorganic nanoparticles and provides a framework for their qualities required as good nanoadsorbents for efficient removal of heavy metals from water. Different inorganic nanoparticles including metals, metal oxides and metal sulfides nanoparticles have been applied as nanoadsorbents to successfully treat water with high contaminations of heavy metals at concentrations greater than 100 mg l
−1
, achieving high adsorption capacities up to 3449 mg g
−1
. It has been identified that the synthesis method, selectivity, stability, regeneration and reusability, and adsorbent separation from solution are critical parameters in deciding on the quality of inorganic nanoadsorbents. Surface functionalized nanoadsorbents were found to possess high selectivity and capacity for heavy metals removal from water even at a very low adsorbent dosage of less than 2 g l
−1
, which makes them better than conventional adsorbents in environmental remediation.
Production optimization, stability and oil emulsifying potential of biosurfactants from selected bacteria isolated from oil-contaminated sites
Authors: Ali Ferdausi , Das Sharup , Hossain Tanim Jabid , Chowdhury Sumaiya Islam , Zedny Subrina Akter , Das Tuhin , Ahmed Chowdhury Mohammad Nazmul , Uddin Mohammad Seraj
Published: October 2021

Oil pollution is of increasing concern for environmental safety and the use of microbial surfactants in oil remediation has become inevitable for their efficacy and ecofriendly nature. In this work, biosurfactants of bacteria isolated from oil-contaminated soil have been characterized. Four potent biosurfactant-producing strains (SD4, SD11, SD12 and SD13) were selected from 27 isolates based on drop collapse assay and emulsification index, and identified as species belonging to
Bacillus
,
Burkholderia
,
Providencia
and
Klebsiella
, revealed from their 16S rRNA gene-based analysis. Detailed morphological and biochemical characteristics of each selected isolate were determined. Their growth conditions for maximum biosurfactant production were optimized and found quite similar among the four isolates with a pH of 3.0 and temperature 37°C after 6 or 7 days of growth on kerosene. The biosurfactants of SD4, SD11 and SD12 appeared to be glycolipids and that of SD13 a lipopeptide. Emulsification activity of most of the biosurfactants was stable at low and high temperatures (4–100°C), a wide range of pH (2–10) and salt concentrations (2–7% NaCl). Each biosurfactant showed antimicrobial activity against two or more pathogenic bacteria. The biosurfactants were well-capable of emulsifying kerosene, diesel and soya bean, and could efficiently degrade diesel.
Animal contests and microplastics: evidence of disrupted behaviour in hermit crabsPagurus bernhardus
Authors: Cunningham Eoghan M. , Mundye Amy , Kregting Louise , Dick Jaimie T. A. , Crump Andrew , Riddell Gillian , Arnott Gareth
Published: October 2021

Microplastics are ubiquitous in global marine systems and may have negative impacts on a vast range of species. Recently, microplastics were shown to impair shell selection assessments in hermit crabs, an essential behaviour for their survival. Hermit crabs also engage in ‘rapping’ contests over shells, based on cognitive assessments of shell quality and opponent fighting ability and, hence, are a useful model species for examining the effects of microplastics on fitness-relevant behaviour in marine systems. Here, we investigated how a 5-day microplastic exposure (25 microplastics/litre) affected the dynamics and outcome of 120 staged hermit crab contests. Using a 2 × 2 factorial design, we examined how microplastics (i.e. presence or absence) and contestant role (i.e. attacker or defender) affected various behavioural variables. Significantly higher raps per bout were needed to evict microplastic-treated defenders when attackers were pre-exposed to control conditions (i.e. no plastic). Also, significantly longer durations of rapping bouts were needed to evict control-treated defenders when attackers were pre-exposed to microplastics. We suggest that microplastics impaired defenders' ability to identify resource holding potential and also affected attackers’ rapping strength and intensity during contests. These impacts on animal contests indicate that microplastics have broader deleterious effects on marine biota than currently recognized.
Two-dimensional numerical studies of particle motion and deposition in the channel of diesel particulate filters
Authors: Wang Xiaolong , Deng Yangbo , Liu Yang
Published: October 2021

A numerical investigation on the soot laden flow of gas in a partial diesel particulate filter (PDPF) is presented based on solving the momentum equations for a continuous phase in the Euler frame and the motion equations for the dispersed phase in the Lagrangian frame. The interaction between the gas phase and the particles is considered as a one-way coupling for dilute particle concentration, while the interaction between particles and porous wall is implemented through user-definedsubroutines. To accurately track motion of nanoscale particles, the Brownian excitation and drag force as well as partial slip are taken into account in the particulate motion equation. Two methods are used to verify the gas flow model and reasonable agreements for both comparisons are observed. The effects of inlet velocity, wall permeability and particle size on the filtration efficiency and deposition distribution of the particles along with wall surface of inlet channel are quantitatively studied. The results show that (i) wall permeability plays the primary role in determining the filtration efficiency of PDPF, (ii) both upstream velocity and particle size have an effect on the initial deposition position of particles and (iii) filtration efficiency of PDPF is not markedly proportional to gas flow into inlet channels at a low wall permeability.
Re-assessing the phylogenetic status and evolutionary relationship of Forest Owlet [Athene blewitti(Hume 1873)] using genomic data
Authors: Vinay K.L , Natesh Meghana , Mehta Prachi , Jayapal Rajah , Mukherjee Shomita , Robin V.V.
Published: October 2021

Phylogenetic relationships are often challenging to resolve in recent/younger lineage when only a few loci are used. Ultra Conserved Elements (UCE) are highly conserved regions across taxa that help resolve shallow and deep divergences. We utilized UCEs harvested from whole genomes to assess the phylogenetic position and taxonomic affiliation of an endangered endemic owlet in the family Strigidae – the Forest OwletAthene blewitti. The taxonomic placement of this species has been revised multiple times. A multigene study attempted to address the question but showed a discrepancy across datasets in its placement of the species within genusAthene. We assembled a dataset of 5018 nuclear UCE loci with increased taxon sampling. Forest Owlet was found to be an early split from theAtheneclade but sister to otherAthene;and consistent across three approaches - maximum likelihood, bayesian, and the multispecies coalescence. Divergence dating using fossil calibrations suggest that theAthenelineage split from its ancestor about 7.6Mya, and the Forest Owlet diverged about 5.2Mya, consistent with previous multigene approaches. Despite osteological differences from otherAthene, we suggest the placement of the Forest Owlet as a member of theAtheneto emphasize its evolutionary relationship.

Graphical Abstract

HIGHLIGHTS

Phylogenomics using genome-wide nuclear markers yielded a well-supported topology forAtheneandGlaucidiumlineages.

Three different methods of phylogenetic tree construction showed that Forest Owlet is an early split from all otherAthenespecies.

Divergence dating in the bayesian framework puts the Forest Owlet age between 5.0my to 5.5my.
Cross-feeding shapes both competition and cooperation in microbial ecosystems
Authors: Mehta Pankaj , Marsland Robert
Published: October 2021

Recent work suggests that cross-feeding – the secretion and consumption of metabolic biproducts by microbes – is essential for understanding microbial ecology. Yet how cross-feeding and competition combine to give rise to ecosystem-level properties remains poorly understood. To address this question, we analytically analyze the Microbial Consumer Resource Model (MiCRM), a prominent ecological model commonly used to study microbial communities. Our mean-field solution exploits the fact that unlike replicas, the cavity method does not require the existence of a Lyapunov function. We use our solution to derive new species-packing bounds for diverse ecosystems in the presence of cross-feeding, as well as simple expressions for species richness and the abundance of secreted resources as a function of cross-feeding (metabolic leakage) and competition. Our results show how a complex interplay between competition for resources and cooperation resulting from metabolic exchange combine to shape the properties of microbial ecosystems.
phylogatR: Phylogeographic data aggregation and repurposing
Authors: Pelletier Tara A , Parsons Danielle J , Decker Sydney K , Crouch Stephanie , Franz Eric , Ohrstrom Jeffery , Carstens Bryan C
Published: October 2021

Patterns of genetic diversity within species contain information about the history of that species, including how they have responded to historical climate change and how easily the organism is able to disperse across its habitat. More than 40,000 phylogeographic and population genetic investigations have been published to date, each collecting genetic data from hundreds of samples. Despite these millions of data points, meta-analyses are challenging because the synthesis of results across hundreds of studies, each using different methods and forms of analysis, is a daunting and time-consuming task. It is more efficient to proceed by repurposing existing data and using automated data analysis. To facilitate data repurposing, we created a database (phylogatR)that aggregates data from different sources and conducts automated multiple sequence alignments and data curation to provide users with nearly ready-to-analyze sets of data for thousands of species. Two types of scientific research will be made easier byphylogatR, large meta-analyses of thousands of species that can address classic questions in evolutionary biology and ecology and student- or citizen-science based investigations that will introduce a broad range of people to the analysis of genetic data.phylogatRenhances the value of existing data via the creation of software and web-based tools that enable these data to be recycled and reanalyzed and increase accessibility to big data for research labs and classroom instructors with limited computational expertise and resources.
gJLS2: An R package for generalized joint location and scale analysis in X-inclusive genome-wide association studies
Authors: Deng Wei Q. , Sun Lei
Published: October 2021

A joint analysis of location and scale can be a powerful tool in genome-wide association studies to uncover previously overlooked markers that influence a quantitative trait through both mean and variance, as well as to prioritize candidates for gene-environment interactions. This approach has recently been generalized to handle related samples, dosage data, and the analytically challenging X-chromosome. We disseminate the latest advances in methodology through a user-friendly R software package with added functionalities to support genome-wide analysis on individual-level or summary-level data. The implemented R package can be called from PLINK or directly in a scripting environment, to enable a streamlined genome-wide analysis for biobank-scale data. Application results on individual-level and summary-level data highlight the advantage of the joint test to discover more genome-wide signals as compared to a location or scale test alone. We hope the availability of gJLS2 software package will encourage more scale and/or joint analyses in large-scale datasets, and promote the standardized reporting of their p-values to be shared with the scientific community.
Local adaptation and spatiotemporal patterns of genetic diversity revealed by repeated sampling of Caenorhabditis elegans across the Hawaiian Islands
Authors: Crombie Timothy A. , Battlay Paul , Tanny Robyn E. , Evans Kathryn S. , Buchanan Claire M. , Cook Daniel E. , Dilks Clayton M. , Stinson Loraina A. , Zdraljevic Stefan , Zhang Gaotian , Roberto Nicole M. , Lee Daehan , Ailion Michael , Hodgins Kathryn A. , Andersen Erik C.
Published: October 2021

The nematode Caenorhabditis elegans is among the most widely studied organisms, but relatively little is known about its natural ecology. Wild C. elegans have been isolated from both temperate and tropical climates, where they feed on bacteria associated with decomposing plant material. Genetic diversity is low across much of the globe but high in the Hawaiian Islands and across the Pacific Rim. The high genetic diversity found there suggests that: (1) the origin of the species lies in Hawaii or the surrounding Pacific Rim; and (2) the ancestral niche of the species is likely similar to the Hawaiian niche. A recent study of the Hawaiian niche found that genetically distinct groups appeared to correlate with elevation and temperature, but the study had a limited sample size. To better characterize the niche and genetic diversity of C. elegans on the Hawaiian Islands and to explore how genetic diversity might be influenced by local adaptation, we repeatedly sampled nematodes over a three-year period, measured various environmental parameters at each sampling site, and whole-genome sequenced the C. elegans isolates that we identified. We found that the typical Hawaiian C. elegans niche is moderately moist native forests at high elevations (500 to 1500 meters) where temperatures are cool (15 to 20°C). We measured levels of genetic diversity and differentiation among Hawaiian strains and found evidence of seven genetically distinct groups distributed across the islands. Then, we scanned these genomes for signatures of local adaptation and identified 18 distinct regions that overlap with hyperdivergent regions, which are likely maintained by balancing selection and enriched for genes related to environmental sensing, xenobiotic detoxification, and pathogen resistance. These results provide strong evidence of local adaptation among Hawaiian C. elegans and a possible genetic basis for this adaptation.
Non-micronized and micronized curcumin do not prevent the behavioral and neurochemical effects induced by acute stress in zebrafish
Authors: Sachett Adrieli , Gallas-Lopes Matheus , Benvenutti Radharani , Marcon Matheus , Linazzi Amanda M. , Aguiar Gean P. S. , Herrmann Ana P. , Oliveira J. Vladimir , Siebel Anna M. , Piato Angelo
Published: October 2021

Curcumin, a polyphenol extracted from the rhizome of Curcuma longa L. (Zingiberaceae), presents neuroprotective properties and can modulate neuronal pathways related to mental disorders. However, curcumin has low bioavailability, which can compromise its use. The micronization process can reduce the mean particle diameter and improve this compound’s bioavailability and therapeutic potential. In this study, we compared the behavioral (in the open tank test, OTT) and neurochemical (thiobarbituric acid reactive substances (TBARS) and non-protein thiols (NPSH) levels) effects of non-micronized curcumin (CUR, 10 mg/kg, i.p.) and micronized curcumin (MC, 10 mg/kg, i.p.) in adult zebrafish subjected to 90-minute acute restraint stress (ARS). ARS increased the time spent in the central area and the number of crossings and decreased the immobility time of the animals. These results suggest an increase in locomotor activity and a decrease in thigmotaxis behavior in the OTT. Furthermore, ARS also induced oxidative damage by increasing TBARS and decreasing NPSH levels. ARS-induced behavioral and biochemical effects were not blocked by any curcumin preparation. Therefore, we suppose that curcumin does not have anti-stress effects on the ARS in zebrafish.
Flagellin FLiC Enhances Resistance of Upland Cotton toVerticillium dahliae
Authors: Zhou Heng , Xie Yijing , Wang Yi , Zhu Heqin , Tang Canming
Published: October 2021

The mechanism by which flagellin induces an immune response in plants is still unclear. The purpose of this study is to reveal the effect and mechanism of flagellin in inducing plants to produce an immune response to increase the resistance toVerticillium dahliae(VD). The full-length flagellin gene C (FliC) was cloned from an endophytic bacteria (Pseudomonas) in the root of upland cotton cultivar Zhongmiansuo 41. The FliC protein purified in vitro has 47.50% and 32.42% biocontrol effects on resistant and susceptible cotton cultivars, respectively. FLiC can induce allergic reactions in tobacco leaf cells and immune responses in cotton plants. Smearing FLiC to cotton and performing RNA-seq analysis, it is significantly enriched in the activity of positive ion transporters such as potassium ions and calcium ions (Ca2+), diterpenoid biosynthesis, phenylpropane biosynthesis and other disease-resistant metabolic pathways. FLiC inhibits the expression of calcium antiporter activity gene (GhCAA) to accelerate intracellular Ca2+influx and stimulate the increase of intracellular hydrogen peroxide (H2O2) and nitric oxide (NO) content. The coordinated regulation of Ca2+, H2O2and NO enhances disease resistance. The resistance of transgenicFLiCgene Arabidopsis to VD was significantly improved. TheFLiCgene can be used as an anti-VD gene and as a regulator to improve resistance to VD.
Glycosuria alters uropathogenicEscherichia coliglobal gene expression and virulence
Authors: Islam Md. Jahirul , Bagale Kamal , John Preeti P , Kurtz Zachary , Kulkarni Ritwij
Published: October 2021

UropathogenicEscherichia coli(UPEC) is the principal etiology of more than half of urinary tract infections (UTI) in humans with diabetes mellitus. Epidemiological data and studies in mouse model of ascending UTI have elucidated various host factors responsible for increasing the susceptibility of diabetic hosts to UPEC-UTI. In contrast, the nature of alterations in UPEC physiology mediated by diabetic urinary microenvironment and the contributions of altered UPEC physiology in shaping UPEC-UTI pathogenesis in diabetes have not been examined. Our central hypothesis is that glycosuria directly induces urinary virulence of UPEC. We compared virulence characteristics and gene expression in human UPEC strains UTI89 (cystitis) and CFT073 (pyelonephritis) exposed for 2h,in vitroto human urine either in the presence or absence of glycosuria (600mg/dl glucose). Compared to control UPEC exposed to nutrient-rich culture medium LB, glycosuria-exposed UPEC exhibited significant increase in biofilm formation and reduction in the hemagglutination of Guinea pig erythrocytes (a surrogate measure of type 1 piliation). In addition, analysis of UTI89 transcriptome by RNA sequencing revealed that 2h-long,in vitroexposure to glycosuria also significantly alters expression of virulence and metabolic genes central to urinary virulence of UPEC. In summary, our results provide novel insights into how glycosuria-mediated early changes in UPEC fitness may facilitate UTI pathogenesis in the diabetic urinary microenvironment.

IMPORTANCE

UropathogenicEscherichia coli(UPEC) is an important causative agent of urinary tract infections in diabetic humans. We examined the effects ofin vitroexposure to glycosuria (presence of glucose in urine) on the virulence and gene expression by UPEC. Our results show that glycosuria rapidly (in 2h) alters UPEC gene expression, induces biofilm formation, and suppresses hemagglutination. These results offer a novel insight into the pathogenesis of UPEC in the urinary tract.
RNAi screen of RING/U-box domain ubiquitin ligases identifies critical regulators of tissue regeneration in planarians
Authors: Allen John M. , Balagtas Madison , Barajas Elizabeth , Macip Carolina Cano , Zepeda Sarai Alvarez , Iberkleid Ionit , Duncan Elizabeth M. , Zayas Ricardo M.
Published: October 2021

Regenerative processes depend on the interpretation of signals to coordinate cell behaviors. The role of ubiquitin-mediated signaling is known to be important in many cellular and biological contexts, but its role in regeneration is not well understood. To investigate how ubiquitylation impacts tissue regeneration in vivo, we are studying planarians that are capable of regenerating after nearly any injury using a population of stem cells. Here we used RNAi to screen RING/U-box E3 ubiquitin ligases that are highly expressed in planarian stem cells and stem cell progeny. RNAi screening identified nine genes with functions in regeneration, including the spliceosomal factor prpf19 and histone modifier rnf2; based on their known roles in developmental processes, we further investigated these two genes. We found that prpf19 was required for animal survival but not for stem cell maintenance, suggesting a role in promoting cell differentiation. Because RNF2 is the catalytic subunit of the Polycomb Repressive Complex 1 (PRC1), we also examined other putative members of this complex (CBX and PHC). We observed a striking phenotype of regional tissue misspecification in cbx and phc RNAi planarians. To identify genes regulated by PRC1, we performed RNA-seq after knocking down rnf2 or phc. Although these proteins are predicted to function in the same complex, we found that the set of genes differentially expressed in rnf2 versus phc RNAi were largely non-overlapping. Using in situ hybridization, we showed that rnf2 regulates gene expression levels within a tissue type, whereas phc is necessary for the spatial restriction of gene expression, findings consistent with their respective in vivo phenotypes. This work not only uncovered roles for RING/U-box E3 ligases in stem cell regulation and regeneration, but also identified differential gene targets for two putative PRC1 factors required for maintaining cell-type-specific gene expression in planarians.
Macrophage Innate Training Induced by IL-4 and IL-13 Activation Enhances OXPHOS Driven Anti-Mycobacterial Responses
Authors: Lundahl Mimmi L. E. , Mitermite Morgane , Ryan Dylan G. , Case Sarah , Williams Niamh C. , Yang Ming , Lynch Roisin I. , Lagan Eimear , Lebre Filipa , Gorman Aoife L. , Stojkovic Bojan , Bracken Adrian P. , Frezza Christian , Sheedy Fred J. , Scanlan Eoin M. , O’Neill Luke A. J. , Gordon Stephen V. , Lavelle Ed C.
Published: October 2021

Macrophages are a highly adaptive population of innate immune cells. Polarization with IFNγ and LPS into the “classically activated” M1 macrophage enhances pro-inflammatory and microbicidal responses, important for eradicating bacteria such as Mycobacterium tuberculosis. By contrast, “alternatively activated” M2 macrophages, polarized with IL-4, oppose bactericidal mechanisms and allow mycobacterial growth. These activation states are accompanied by distinct metabolic profiles, where M1 macrophages favor near exclusive use of glycolysis, whereas M2 macrophages up-regulate oxidative phosphorylation (OXPHOS). Here we demonstrate that activation with IL-4 and IL-13 counterintuitively induces protective innate memory against mycobacterial challenge. In human and murine models, prior activation with IL-4/13 enhances pro-inflammatory cytokine secretion in response to a secondary stimulation with mycobacterial ligands. In our murine model, enhanced killing capacity is also demonstrated. Despite this switch in phenotype, IL-4/13 trained murine macrophages do not demonstrate M1-typical metabolism, instead retaining heightened use of OXPHOS. Moreover, inhibition of OXPHOS with oligomycin, 2-deoxy glucose or BPTES all impeded heightened pro-inflammatory cytokine responses from IL-4/13 trained macrophages. Lastly, this work identifies that IL-10 attenuates protective IL-4/13 training, impeding pro-inflammatory and bactericidal mechanisms. In summary, this work provides new and unexpected insight into alternative macrophage activation states in the context of mycobacterial infection.
Aged human iPSC-RPE organoid cultures display hallmarks of drusen formation
Authors: Mesch Lena , Pashkovskaia Natalia , Cora Virginia , Pars Selin , Corti Serena , Cipriano Madalena , Loskill Peter , Koertvely Elod , Kustermann Stefan , Mesquida Marina , Kleger Alexander , Liebau Stefan , Achberger Kevin
Published: October 2021

Age-related macular degeneration (AMD) is among the most common causes of irreversible vision loss. Disease progression is strongly associated with age-related pathological changes of retinal pigment epithelial (RPE) cells, such as accumulation of intracellular lipid-containing cell debris, extracellular lipid-rich deposits (drusen) and collagen-rich basal laminar deposits. Current AMD models provide a limited understanding of the complex pathomechanisms, revealing the lack of adequate physiological human AMD models. In this study, we developed anin vitromodel applicable for the exploration of AMD pathomechanisms and risk factors for AMD progression and drusen formation. Advanced 3D culturing technologies allow long-term cultivation of hiPSC-derived RPE organoids (RPEorg) for up to 360 days, which is the time frame necessary for the development of an AMD-like phenotype. Aged RPEorg exhibit hallmarks of AMD and age-related alterations such as increased autofluorescence, accumulation of lipid droplets, calcification, and the formation of extracellular clusters of the drusen-associated proteins such as apolipoprotein E (APOE) and tissue inhibitor of metalloproteinases 3 (TIMP3). Electron microscopy further reveals drusen-like extracellular deposits mimicking the signs of late drusen formation and AMD progression. In summary, our results demonstrate that hiPSC-derived 3D RPEorg provide a promising model to study age-associated RPE pathology and drusen formation. We show here that RPEorg are applicable for disease modelling studies and early stages of drug development and provide the opportunity to uncover inter-individual genetic and epigenetic factors that alter the course of the disease.
Chemical inhibition of auxin inactivation pathway uncovers the metabolic turnover of auxin homeostasis
Authors: Fukui Kosuke , Arai Kazushi , Tanaka Yuka , Aoi Yuki , Kukshal Vandna , Jez Joseph M , Kubes Martin F , Napier Richard , Zhao Yunde , Kasahara Hiroyuki , Hayashi Ken-ichiro
Published: October 2021

The phytohormone auxin, specifically indole-3-acetic acid (IAA) plays a prominent role in plant development. Cellular auxin concentration is coordinately regulated by auxin synthesis, transport, and inactivation to maintain auxin homeostasis; however, the physiological contribution of auxin inactivation to auxin homeostasis has remained elusive. The GH3 genes encode auxin amino acid conjugating enzymes that perform a central role in auxin inactivation. The chemical inhibition of GH3s in planta is challenging because the inhibition of GH3 enzymes leads to IAA overaccumulation that rapidly induces GH3 expression. Here, we developed a potent GH3 inhibitor, designated as kakeimide (KKI), that selectively targets auxin-conjugating GH3s. Chemical knockdown of the auxin inactivation pathway demonstrates that auxin turnover is very rapid (about 10 min), indicating auxin biosynthesis and inactivation dynamically regulate auxin homeostasis.
High levels of origin licensing during Xenopus cleavage divisions ensures complete and timely genome duplication
Authors: Gillespie Peter J. , Kisielewska Jolanta , Mamun Mohammed Al , Khoudoli Guennadi , Creavin Kevin , Score Alan J. , Blow J. Julian
Published: October 2021

Cells face several challenges to completing genome duplication. One challenge is the irreversible stalling of converging replication forks (‘double fork stalls’). Cell types that cannot delay mitotic entry must also ensure that no replication origins are too far apart (the ‘random gap problem’). We show how these challenges can be met in early Xenopus embryos by the very abundant licensing of replication origins: one MCM2-7 double hexamer every ∼250 bp. Licensing does not change nucleosome spacing, consistent with MCM2-7 being assembled onto inter-nucleosomal linker DNA. We show that later embryonic development can occur successfully with a per-cell cycle failure rate of <0.2% in early embryos. The high density of licensed origins in the early embryo reduces cell cycle failures from random gaps and from double fork stalls to levels compatible with subsequent development, suggesting that Xenopus early embryonic cells can ensure complete genome duplication without requiring unconventional replication mechanisms.
CD20+T cells are associated with inflammatory responses in experimental arthritis
Authors: Pineda Miguel , Pan Piaopiao , Wang Yilin , Khan Aneesah , Nyirenda Mukanthu H.
Published: October 2021

CD20+T cells comprise a small but highly inflammatory subset that has been implicated in autoimmunity, including rheumatoid arthritis (RA). We sought to characterise the CD20+T cell subset at the site of inflammation in murine collagen-induced arthritis (CIA) model of RA and investigate the phenotype and functional relevance of CD3+CD20+T cells in the lymph nodes and arthritic joints using flow cytometry and immunohistochemistry. We demonstrate that CD3+CD4+CD20+and CD3+CD8+CD20+T cells are expanded in the draining lymph nodes of CIA mice. In addition, compared to naïve mice and those that did not develop clinical symptoms, CD20 expressing T cells of arthritic mice produced increased levels of pro-inflammatory cytokines (GM-CSF, TNF-a, IL-17, and INF-g). Notably, CD3+CD4+CD20+and CD3+CD8+CD20+T cells of disease mice were enriched with CXCR5+PD-1+T follicular helper cells and CXCR5-PD-1+peripheral T helper cells, subsets of T cells that have been implicated in promoting B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues in RA. Importantly, CD3+CD20+T cells were detected in the inflamed regions in the lymph nodes and paws of arthritic mice. Our findings suggest that CD20+T cells are associated with inflammatory responses in the arthritic joint and may exacerbate pathology by promoting inflammatory B cell responses.
Long-range migration of centrioles to the apical surface of the olfactory epithelium
Authors: Ching Kaitlin , Wang Jennifer T. , Stearns Tim
Published: October 2021

Olfactory sensory neurons (OSNs) in vertebrates detect odorants using multiple cilia, which protrude from the end of the dendrite and require centrioles for their formation. In mouse olfactory epithelium, the centrioles originate in progenitor cells near the basal lamina, often 50 to 100 μm from the apical surface. It is unknown how centrioles traverse this distance or mature to form cilia. Using high-resolution expansion microscopy, we found that centrioles migrate together, with multiple centrioles per group and multiple groups per OSN, during dendrite outgrowth. Centrioles were found by live imaging to migrate slowly, with a maximum rate of 0.18 μm/min. Centrioles in migrating groups were associated with microtubule nucleation factors, but acquired rootletin and appendages only in mature OSNs. The parental centriole had preexisting appendages, formed a single cilium prior to other centrioles, and retained its unique appendage configuration in the mature OSN. We developed an air-liquid interface explant culture system for OSNs and used it to show that centriole migration can be perturbed ex vivo by stabilizing microtubules. We consider these results in the context of a comprehensive model for centriole formation, migration, and maturation in this important sensory cell type.
STOICHIOMETRY OF THE SODIUM PUMP-PHOSPHOLEMMAN REGULATORY COMPLEX
Authors: Seflova Jaroslava , Habibi Nima R. , Yap John Q. , Cleary Sean R. , Fang Xuan , Kekenes-Huskey Peter M. , Espinoza-Fonseca L. Michel , Bossuyt Julie B. , Robia Seth L.
Published: October 2021

The sodium-potassium ATPase (NKA) establishes ion gradients that facilitate many physiological processes. In the heart, NKA activity is regulated by its interaction with phospholemman (PLM, FXYD1). Here we used a novel fluorescence lifetime-based assay to investigate the structure, stoichiometry, and affinity of the NKA-PLM regulatory complex. We observed concentration dependent association of the subunits of NKA-PLM regulatory complex, with avid association of the alpha subunit with the essential beta subunit followed by lower affinity alpha-alpha and alpha-PLM interactions. The data provide the first evidence that the regulatory complex is composed of two alpha subunits associated with two beta subunits, decorated with two PLM regulatory subunits in intact cells. Docking and molecular dynamics simulations generated a structural model of the complex that is consistent with our experimental observations. We propose that alpha-alpha subunit interactions support conformational coupling of the catalytic subunits, which may enhance NKA turnover rate. These observations provide insight into the pathophysiology of heart failure, wherein low NKA expression may be insufficient to support formation of the complete regulatory complex with stoichiometry (alpha-beta-PLM)2.
Topoisomerase II poisons inhibit vertebrate DNA replication through distinct mechanisms
Authors: Van Ravenstein Sabrina X. , Mehta Kavi P. , Kavlashvili Tamar , Byl Jo Ann , Zhao Runxiang , Osheroff Neil , Cortez David , Dewar James M.
Published: October 2021

Topoisomerase II (Top2) unlinks chromosomes during vertebrate DNA replication. Top2 ‘poisons’ are widely-used chemotherapeutics that stabilize Top2 complexes on DNA, leading to cytotoxic DNA breaks. However, it is unclear how these drugs affect DNA replication, which is a major target of Top2 poisons. Using Xenopus egg extracts, we show that the Top2 poisons etoposide and doxorubicin both inhibit DNA replication through different mechanisms. Etoposide induces Top2-dependent DNA breaks and induces Top2-dependent fork stalling by trapping Top2 behind replication forks. In contrast, doxorubicin does not lead to appreciable break formation and instead intercalates into parental DNA to inhibit replication fork progression. In human cells, etoposide stalls replication forks in a Top2-dependent manner, while doxorubicin stalls forks independently of Top2. However, both drugs exhibit Top2-dependent cytotoxicity. Thus, despite shared genetic requirements for cytotoxicity etoposide and doxorubicin inhibit DNA replication through distinct mechanisms.