bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of GWAS and TWAS to elucidate the genetic architecture of natural variation for leaf cuticular conductance in maize
Authors: Lin Meng , Qiao Pengfei , Matschi Susanne , Vasquez Miguel , Ramstein Guillaume P. , Bourgault Richard , Mohammadi Marc , Scanlon Michael J. , Molina Isabel , Smith Laurie G. , Gore Michael A. 
Published: October 2021

AbstractThe cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed. Dissecting the genetic architecture of natural variation for maize leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we performed an integrated genome- and transcriptome-wide association study (GWAS/TWAS) to identify candidate genes putatively regulating variation in leafgc. Of the 22 plausible candidate genes identified, five were predicted to be involved in cuticle precursor biosynthesis and export, two in cell wall modification, nine in intracellular membrane trafficking, and seven in the regulation of cuticle development. A gene encoding an INCREASED SALT TOLERANCE1-LIKE1 (ISTL1) protein putatively involved in intracellular protein and membrane trafficking was identified in GWAS and TWAS as the strongest candidate causal gene. A set of maize nested near-isogenic lines that harbor theISTL1genomic region from eight donor parents were evaluated forgc, confirming the association betweengcandISTL1in a haplotype-based association analysis. The findings of this study provide novel insights into the role of regulatory variants in the development of the maize leaf cuticle, and will ultimately assist breeders to develop drought-tolerant maize for target environments.Sentence summaryWe performed an integrated GWAS/TWAS and identified 22 candidate genes putatively regulating variation in maize leafgc. The association betweengcand the strongest candidate causal gene,ISTL1, was validated with maize nested near-isogenic lines.
RCX – an R package adapting the Cytoscape Exchange format for biological networks
Authors: Auer Florian , Kramer Frank 
Published: October 2021

AbstractMotivationThe Cytoscape Exchange (CX) format is a JSON-based data structure designed for the transmission of biological networks using standard web technologies. It was developed by the network data exchange (NDEx), which itself serves as online commons to share and collaborate on biological networks. Furthermore, the Cytoscape software for the analysis and visualization of biological networks contributes structure elements to capture the visual layout within the CX format. However, there is a fundamental difference between data handling in web standards and R. A manual conversion requires detailed knowledge of the CX format to reproduce and work with the networks.ResultsHere we present a software package to create, handle, validate, visualize and convert networks in CX format to standard data types and objects within R. Networks in this format can serve as a source for biological knowledge, and also capture the results of the analysis of those while preserving the visual layout across all platforms. The RCX package connects the R environment for statistical computing with outside platforms for storage and collaboration, as well as further analysis and visualization of biological networks.AvailabilityRCX is a free and open-source R package, available on Bioconductor from release 3.15 (https://bioconductor.org/packages/RCX) and via GitHub (https://github.com/frankkramer-lab/RCX).Contactflorian.auer@informatik.uni-augsburg.deSupplementary informationSupplementary data are available at Bioinformatics Advances online.
Camel nanobodies broadly neutralize SARS-CoV-2 variants
Authors: Hong Jessica , Kwon Hyung Joon , Cachau Raul , Chen Catherine Z. , Butay Kevin John , Duan Zhijian , Li Dan , Ren Hua , Liang Tianyuzhou , Zhu Jianghai , Dandey Venkata P. , Martin Negin , Esposito Dominic , Ortega-Rodriguez Uriel , Xu Miao , Borgnia Mario J. , Xie Hang , Ho Mitchell 
Published: October 2021

AbstractWith the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two VHH nanobodies (7A3 and 8A2) from dromedary camels by phage display, which have high affinity for the receptor-binding domain (RBD) and broad neutralization activities against SARS-CoV-2 and its emerging variants. Cryo-EM complex structures reveal that 8A2 binds the RBD in its up mode and 7A3 inhibits receptor binding by uniquely targeting a highly conserved and deeply buried site in the spike regardless of the RBD conformational state. 7A3 at a dose of ≥5 mg/kg efficiently protects K18-hACE2 transgenic mice from the lethal challenge of B.1.351 or B.1.617.2, suggesting that the nanobody has promising therapeutic potentials to curb the COVID-19 surge with emerging SARS-CoV-2 variants.One-Sentence SummaryDromedary camel (Camelus dromedarius) VHH phage libraries were built for isolation of the nanobodies that broadly neutralize SARS-CoV-2 variants.
Major sex differences in allele frequencies for X chromosome variants in the 1000 Genomes Project data
Authors: Wang Zhong , Sun Lei , Paterson Andrew D. 
Published: October 2021

AbstractAn unexpectedly high proportion of SNPs on the X chromosome in the 1000 Genomes Project phase 3 data were identified with significant sex differences in minor allele frequencies (sdMAF). sdMAF persisted for many of these SNPs in the recently released high coverage whole genome sequence, and it was consistent between the five super-populations. Among the 245,825 common biallelic SNPs in phase 3 data presumed to be high quality, 2,039 have genome-wide significant sdMAF (p-value <5e-8). sdMAF varied by location: (NPR)=0.83%, pseudo-autosomal region (PAR1)=0.29%, PAR2=13.1%, and PAR3=0.85% of SNPs had sdMAF, and they were clustered at the NPR-PAR boundaries, among others. sdMAF at the NPR-PAR boundaries are biologically expected due to sex-linkage, but have generally been ignored in association studies. For comparison, similar analyses found only 6, 1 and 0 SNPs with significant sdMAF on chromosomes 1, 7 and 22, respectively. Future X chromosome analyses need to take sdMAF into account.
Of Biofilms and Beehives: An Analogy-Based Instructional Tool to Introduce Biofilms to High-School and Undergraduate Students
Authors: Kadam Snehal , Chattopadhyay Ankita , Kaushik Karishma S 
Published: October 2021

AbstractThe concept of biofilms and biofilm-based research is largely absent or minimally described in high school and undergraduate life science curriculum. While it is well-established that microbes, such as bacteria and fungi most often exist in multicellular biofilm communities, descriptions in standard biology textbooks continue to focus on the single-celled form of microbial life. We have developed an analogy-based instructional tool to introduce and explain biofilms to high school and undergraduate students. The module employs an analogy with beehives, given that biofilms and beehives are both ‘superorganism’ states, to explain key biofilm features such as development and structure, chemical communication, division of labor and emergent properties. We delivered this analogy based learning tool to a cohort of 49 high school and undergraduate students, and based on participant feedback and learnings, present a formal evaluation of the instructional tool. Further, we outline prerequisites and learning approaches that can enable the delivery of this module in classroom and virtual learning settings, including suggestions for pre-lesson reading, student-centred interactive activities, and specific learning objectives. Taken together, this instructional analogy holds potential to serve as an educational tool to introduce biofilms in high school and undergraduate curricula in a relatable and comprehensible manner.
Patient-derived endometrial organoids from MRKH patients: Insight in disease causing pathways
Authors: Brucker Sara Y. , Hentrich Thomas , Schulze-Hentrich Julia M. , Pietzsch Martin , Wajngarten Noel , Singh Anjali Ralhan , Rall Katharina , Koch André 
Published: October 2021

AbstractThe uterus is responsible for the nourishment and mechanical protection of the developing embryo and fetus and is an essential part in mammalian reproduction. The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. Although heavily studied, the cause of the disease is still enigmatic. Current research in the field of MRKH mainly focusses on DNA-sequencing efforts and, so far, failed to decipher the nature and heterogeneity of the disease, thereby holding back scientific and clinical progress. Here, we developed long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically, they share great similarity with healthy control organoids and are surprisingly fully hormone responsive. Transcriptome analyses, however, identified an array of dysregulated genes that point at potentially disease-causing pathways altered during the development of the female reproductive tract. We consider the endometrial organoid cultures to be a powerful research tool that promise to enable an array of studies into the pathogenic origins of MRKH syndrome and possible treatment opportunities to improve patient quality of life.
Climate-driven variation in biotic interactions provides a narrow and variable window of opportunity for an insect herbivore at its ecological margin
Authors: Stewart James E. , Maclean Ilya M.D. , Trujillo Gara , Bridle Jon , Wilson Robert J. 
Published: October 2021

AbstractClimate-driven geographic range shifts have been associated with transitions between dietary specialism and generalism at range margins. The mechanisms underpinning these often transient niche breadth modifications are poorly known, but utilisation of novel resources likely depends on phenological synchrony between the consumer and resource. We use a climate-driven range and host shift by the butterflyAricia agestisto test how climate-driven changes in host phenology and condition affect phenological synchrony, and consider implications for host use.Our data suggest that the perennial plant which was the primary host before range expansion is a more reliable resource than the annual Geraniaceae upon which the butterfly has become specialised in newly colonised parts of its range. In particular, climate-driven phenological variation in the novel hostGeranium dissectumgenerates a narrow and variable ‘window of opportunity’ for larval productivity in summer. Therefore, although climatic change may allow species to shift hosts and colonise novel environments, specialisation on phenologically-limited hosts may not persist at ecological margins as climate change continues. We highlight the potential role for phenological (a)synchrony in determining lability of consumer-resource associations at range margins, and the importance of considering causes of synchrony in biotic interactions when predicting range shifts.
Sex differences in migraine: A twin study
Authors: Morgan Fitzgerald , Saelzler Ursula G. , Panizzon Matthew S. 
Published: October 2021

AbstractMigraine is a neurological disorder with a prominent sex difference such that two thirds of sufferers are female. The mechanisms behind the preponderance of migraine in women have yet to be elucidated. With data on 51,872 participants from the Swedish Twin Registry, we report results from two distinct analyses intended to clarify the degree to which genetic and environmental factors contribute to sex differences in migraine. First, we fit a sex-limitation model to determine if quantitative genetic differences (i.e., is migraine equally heritable across men and women) and/or qualitative genetic differences (i.e., are different genes involved in migraine across men and women) were present. Next, we used a multilevel logistic regression model to compare the prevalence of migraine in individuals from opposite-sex and same-sex twin pairs to determine whether differences in the prenatal hormone environment contribute to migraine risk. In the final analytic sample, women were found to have a significantly higher rate of migraine without aura relative to men (17.6% vs 5.5%). The results from an ADE sex-limitation model indicate that migraine is equally heritable in men and women, with a broad sense heritability of .45, (95% CI = .40 - .50), while results from a reduced AE sex-limitation model provide subtle evidence for differences in the genes underlying migraine across men and women. The logistic regression analysis revealed a significant increase in migraine risk for females with a male co-twin relative to females with a female co-twin (OR = 1.51, 95% CI = 1.26 – 1.81). These results suggest that the prominent sex difference in migraine prevalence is not entirely accounted for by genetic factors, while demonstrating that masculinization of the prenatal environment may increase migraine risk for females. This effect points to a potential prenatal neuroendocrine factor in the development of migraine.
Visuomotor adaptation modulates the clustering of sleep spindles into trains
Authors: Solano Agustín , Riquelme Luis A. , Perez-Chada Daniel , Della-Maggiore Valeria 
Published: October 2021

ABSTRACTSleep spindles are thought to promote memory consolidation. Recently, we have shown that visuomotor adaptation (VMA) learning increases the density of spindles and promotes the coupling between spindles and slow oscillations, locally, with the level of spindle-SO synchrony predicting overnight memory retention. Yet, growing evidence suggests that the rhythmicity in spindle occurrence may also influence the stabilization of declarative and procedural memories. Here, we examined if VMA learning promotes the temporal organization of sleep spindles into trains. We found that VMA increased the proportion of spindles and spindle-SO couplings in trains. In agreement with our previous work, this modulation was observed over the contralateral hemisphere to the trained hand, and predicted overnight memory retention. Interestingly, spindles grouped in a cluster showed greater amplitude and duration than isolated spindles. The fact that these features increased as a function of train length, provides evidence supporting a biological advantage of this temporal arrangement. Our work opens the possibility that the periodicity of NREM oscillations may be relevant in the stabilization of procedural memories.CONTRIBUTION STATEMENTEver since the discovery of memory systems, the study of the mechanisms supporting the consolidation of declarative and procedural memories has progressed somewhat in parallel. We now know, however, that structures originally thought of as purely declarative such as the hippocampus, participate in the consolidation of procedural tasks. Recently, we showed that sleep predicts long-term motor memory through the local synchrony between fast sleep spindles and slow oscillations, a mechanism initially described for the consolidation of declarative memories. Novel evidence has linked the rhythmicity in the occurrence of spindles to memory stabilization. This framework proposes that temporally clustered spindles into trains of two or more separated by 3-6 seconds, may favor the reinstatement and subsequent reprocessing of previously acquired memories. This temporal arrangement may facilitate mnemonic replay and neocortical integration. In the present study, we show that motor learning promotes the organization of spindles into trains, locally, over the contralateral hemisphere, and that this modulation predicts overnight memory retention. Spindle grouping also augmented the proportion of spindle-SO couplings in trains. Importantly, spindles in a cluster increased their duration and amplitude as a function of train length, pointing to a physiological benefit of this temporal organization.
Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells from HIV+ Controllers and Non-Controllers
Authors: George Ashley F. , Luo Xiaoyu , Neidleman Jason , Hoh Rebecca , Vohra Poonam , Thomas Reuben , Shin Min-Gyoung , Lee Madeline J. , Blish Catherine A. , Deeks Steven G. , Greene Warner C. , Lee Sulggi A. , Roan Nadia R. 
Published: October 2021

AbstractT and natural killer (NK) cells are effector cells with key roles in anti-HIV immunity, including in lymphoid tissues, the major site of HIV persistence. In this study, we used 42-parameter CyTOF to conduct deep phenotyping of paired blood- and lymph node (LN)-derived T and NK cells from three groups of HIV+ aviremic individuals: elite controllers, and antiretroviral therapy (ART)-suppressed individuals who had started therapy during chronic vs. acute infection, the latter of which is associated with better outcomes. We found that acute-treated individuals are enriched for specific subsets of T and NK cells, including blood-derived CD56-CD16+ NK cells previously associated with HIV control, and LN-derived CD4+ T follicular helper cells with heightened expansion potential. An in-depth comparison of the features of the cells from blood vs. LNs of individuals from our cohort revealed that T cells from blood were more activated than those from LNs. By contrast, LNs were enriched for follicle-homing CXCR5+ CD8+ T cells, which expressed increased levels of inhibitory receptors and markers of survival and proliferation as compared to their CXCR5-counterparts. In addition, a subset of memory-like CD56brightTCF1+ NK cells was enriched in LNs relative to blood. These results together suggest unique T and NK cell features in acute-treated individuals, and highlight the importance of examining effector cells not only in blood but also the lymphoid tissue compartment, where the reservoir mostly persists, and where these cells take on distinct phenotypic features.
In vitro characterisation and clinical evaluation of the diagnostic accuracy of a new antigen test for SARS-CoV-2 detection
Authors: Montoya J.J. , Rubio J.M. , Ouahid Y. , Lopez A. , Madejon A. , Gil-Garcia A.I. , Hannam R.J. , Butler H.R.E. , Castan P. 
Published: October 2021

AbstractBackground and aimsQuick, user-friendly and sensitive diagnostic tools are the key to controlling the spread of the SARS-CoV-2 pandemic in the new epidemiologic landscape. The aim of this work is to characterise a new Covid-19 antigen test that uses an innovative chromatographic Affimer®-based technology designed for the qualitative detection of SARS-CoV-2 antigen. As rapid technology to detect Covid-19, the test was extensively characterised in vitro. Once the analytical parameters of performance were set, the test system was challenged in a test field study. The aim of this study was to evaluate its diagnostic accuracy, as compared by the gold standard RT-PCR and other existing lateral flow tests.
A Novel Indicator for COVID-19 Pandemic Assessment and Comparison
Authors: Mukherjee Kanchan 
Published: October 2021

AbstractIntroductionIn an increasingly globalized world, no country can remain immune to the effect of the COVID-19 pandemic. The pandemic has exposed the need for effective public health surveillance in the interest of global health security. However, current indicators are limited in doing a comparative intercountry assessment and comparison because of variation in testing rates and reporting standards. Hence, this study attempts at addressing this gap.MethodsThe study proposes incremental change in cases per testing rate (ICTR) as an indicator for doing cross country comparison of the pandemic progress. The equation for calculating this indicator is explained in this study. This is followed by measuring its strength of association and predictive power for determining change in SARS-CoV-2 cases in five countries (USA, UK, India, Pakistan and Bangladesh).Results and discussionICTR was found to have a significantly higher strength of association and predictive power (than the existing indicator-test positivity rate) for determining change in cases over different time periods. Using ICTR, cross country comparison was done for the five countries for15 months to draw deeper insights into the progress of the pandemic.ConclusionsThe study finds ICTR to be a suitable indicator for intercountry comparison and intracountry monitoring of the pandemic, which would be useful for global COVID-19 surveillance.
A Potential Novel COVID-19 Vaccine With RBD-HR1/HR2 Hexamer Structure
Authors: Liu Hongbo , Gao Xiang , Wang Guoyong , Zhang Jianjun , Zhou Jiajie , Wei Tingting , Zhang Yu , Liu Yujiao , Piao Jinhua , Zhang Qiulei , Wang Yayuan , Ma Xin , Zhu Xiaoting , Rao Yikun , Xia Wenjuan , Xie Heng , Zhang Wei 
Published: October 2021

ABSTRACTThe COVID-19 pandemic and the continued spreading of the SARS-CoV-2 variants have brought a grave public health consequence and severely devastated the global economy with recessions. Vaccination is considered as one of the most promising and efficient methods to end the COVID-19 pandemic and mitigate the disease conditions if infected. Although a few vaccines have been developed with an unprecedented speed, scientists around the world are continuing pursuing the best possible vaccines with innovations. Comparing to the expensive mRNA vaccines and attenuated/inactivated SARS-CoV-2 vaccines, recombinant protein vaccines have certain advantages, including their safety (non-virus components), potential stronger immunogenicity, broader protection, ease of scaling-up production, reduced cost, etc. In this study, we reported a novel COVID-19 vaccine generated with RBD-HR1/HR2 hexamer that was creatively fused with the RBD domain and heptad repeat 1 (HR1) or heptad repeat 2 (HR2) to form a dumbbell-shaped hexamer to target the spike S1 subunit. The novel hexamer COVID-19 vaccine induced high titers of neutralizing antibody in mouse studies (>100,000), and further experiments also showed that the vaccine also induced an alternative antibody to the HR1 region, which probably alleviated the drop of immunogenicity from the frequent mutations of SARS-CoV-2.
Tissue-resident memory T cells mediate mucosal immunity to recurrent urinary tract infection
Authors: Rousseau Matthieu , Mariano Livia Lacerda , Canton Tracy , Ingersoll Molly A 
Published: October 2021

AbstractUrinary tract infection (UTI) is one of the most prevalent human bacterial infections. New therapeutic approaches, including vaccination and immunotherapy, are urgently needed to combat the rapid global dissemination of multidrug-resistant uropathogens. Development of therapies is impeded by an incomplete understanding of memory development during UTI. Here, we found that reducing bacterial load early in infection, by reducing the inoculum or with antibiotics after infection, completely abrogated the protective memory response. We observed a mixed T helper cell polarization, comprised of Th1, Th2, and Th17 T cells, among T cells infiltrating the bladder during primary infection. Thus, we hypothesized that reducing antigen load altered T helper cell polarization leading to poor memory. Surprisingly, however, T helper cell polarization was unchanged in these scenarios. Instead, we uncovered a population of tissue resident memory (TRM) T cells that was significantly reduced in the absence of sufficient antigen. Demonstrating that TRMcells are necessary for immune memory, transfer of lymph node or spleen-derived infection-experienced T cells to naïve animals did not confer protection against infection. Supporting that TRMcells are sufficient to protect against recurrent UTI, animals depleted of systemic T cells, or treated with FTY720 to block memory lymphocyte migration from lymph nodes to infected tissue, were equally protected compared to unmanipulated mice against a second UTI. Thus, we uncovered an unappreciated key role for TRMcells in the memory response to bacterial infection in this mucosa, providing a target for non-antibiotic-based immunotherapy and/or new vaccine strategies to prevent recurrent UTI.One Sentence SummaryTRMare necessary and sufficient for memory to recurrent UTI