bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-specific distribution and classification ofWolbachiainfections and mitochondrial DNA haplogroups inAedes albopictusfrom the Indo-Pacific
Authors: Yang Qiong , Chung Jessica , Robinson Katie L. , Schmidt Thomas L. , Ross Perran A. , Liang Jiaxin , Hoffmann Ary A. 
Published: January 2022

AbstractThe arbovirus vectorAedes albopictus(Asian tiger mosquito) is common throughout the Indo-Pacific region, where most global dengue transmission occurs. We analysed population genomic data and tested for cryptic species in 160Ae. albopictussampled from 16 locations across this region. We found no evidence of crypticAe. albopictusbut found multiple intraspecific COI haplotypes partitioned into groups representing three Asian lineages: East Asia, Southeast Asia and Indonesia. Papua New Guinea (PNG), Vanuatu and Christmas Island shared recent coancestry, and Indonesia and Timor-Leste were likely invaded from East Asia. We used a machine learning trained on morphologically sexed samples to classify sexes using multiple genetic features and then characterized thewAlbA andwAlbBWolbachiainfections in 664 other samples. ThewAlbA andwAlbB infections as detected by qPCR showed markedly different patterns in the sexes. For females, most populations had a very high double infection incidence, with 67% being the lowest value (from Timor-Leste). For males, the incidence of double infections ranged from 100% (PNG) to 0% (Vanuatu). Only 6 females were infected solely by thewAlbA infection, while rare uninfected mosquitoes were found in both sexes. ThewAlbA andwAlbB densities varied significantly among populations. For mosquitoes from Torres Strait and Vietnam, thewAlbB density was similar in single-infected and superinfected (wAlbA andwAlbB) mosquitoes. There was a positive association betweenwAlbA andwAlbB infection densities in superinfectedAe. albopictus. Our findings provide no evidence of cryptic species ofAe. albopictusin the region and suggest site-specific factors influencing the incidence ofWolbachiainfections and their densities. We also demonstrate the usefulness of SNPs as sex-specific mosquito markers. The results provide baseline data for the exploitation ofWolbachia-induced cytoplasmic incompatibility (CI) in dengue control.
Toxoplasma ceramide synthases: a curious case of gene duplication, divergence and key functionality
Authors: Koutsogiannis Zisis , Mina John G. , Albus Christin A. , Kol Matthijs A. , Holthuis Joost C. M. , Pohl Ehmke , Denny Paul W. 
Published: January 2022

AbstractToxoplasma gondii is an obligate, intracellular eukaryotic apicomplexan protozoan parasite that can cause foetal damage and abortion in both animals and humans. Sphingolipids have indispensable functions as signaling molecules and are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Ceramide is the precursor for all sphingolipids, and here we report the identification, localisation and analyses of the Toxoplasma ceramide synthases TgCerS1 and TgCerS2 and, using a conditional gene regulation approach, establish their roles in pathogenicity and parasite fitness. Interestingly, we observed that whilst TgCerS1 was a fully functional orthologue of the yeast Lag1p capable of catalysing the conversion of sphinganine to ceramide, in contrast TgCerS2 was catalytically inactive. Furthermore, genomic deletion of TgCerS1 using CRISPR/Cas-9 led to viable but slow growing parasites indicating its importance but not indispensability. In contrast, genomic knock out of TgCerS2 was only accessible utilising the rapamycin-inducible Cre recombinase system. Surprisingly, the results demonstrated that this ‘pseudo’ ceramide synthase, TgCerS2, has an even greater role in parasite fitness than its catalytically active orthologue (TgCerS1). Phylogenetic analyses indicated that, as in humans and plants, the ceramide synthase isoforms found in Toxoplasma and other Apicomplexa arose through gene duplication. However, in the Apicomplexa the duplicated copy subsequently evolved into a non-functional ‘pseudo’ ceramide synthase. This arrangement is unique to the Apicomplexa and further illustrates the unusual biology that characterize these protozoan parasites, a feature that could potentially be exploited in the development of new antiprotozoals.Author SummarySphingolipids, essential and ubiquitous lipids in the Eukaryota, are both synthesized and scavenged by the parasitic apicomplexan protozoa, including Toxoplasma gondii. Ceramide is the precursor for all sphingolipids and here we report the identification, localisation and analyses of the Toxoplasma ceramide synthases TgCerS1 and TgCerS2. Surprisingly, whilst TgCerS1 was fully functional, catalysing the conversion of sphinganine to ceramide, TgCerS2 was catalytically inactive. However, we demonstrated that this ‘pseudo’ ceramide synthase has an even greater role in parasite fitness than the catalytically active TgCerS1. Phylogenetic analyses indicated that these isoforms arose through gene duplication and the duplicated copy subsequently evolved into the ‘pseudo’ ceramide synthase. This arrangement is unique to the Apicomplexa and further illustrates the highly unusual biology that characterizes these protozoan parasites, a feature that could potentially be exploited for the development of new antiprotozoals.
Prevalence and disease expression of pathogenic and likely pathogenic variants associated with inherited cardiomyopathies in the general population
Authors: Bourfiss Mimount , van Vugt Marion , Alasiri Abdulrahman I. , Ruijsink Bram , van Setten Jessica , Schmidt Amand F. , Dooijes Dennis , Puyol-Antón Esther , Velthuis Birgitta K. , van Tintelen J. Peter , te Riele Anneline S.J.M. , Baas Annette F. , Asselbergs Folkert W. 
Published: January 2022

AbstractBackgroundPathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are recommended to be reported as secondary findings in genome sequencing studies. This provides opportunities for early diagnosis, but also fuels uncertainty in variant carriers (G+), since disease penetrance is incomplete. We assessed the prevalence and disease expression of G+ in the general population.MethodsWe identified pathogenic and likely pathogenic variants associated with ARVC, DCM and/or HCM in 200,643 UK Biobank individuals, who underwent whole exome sequencing. We calculated the prevalence of G+ and analysed the frequency of cardiomyopathy/heart failure diagnosis. In undiagnosed individuals, we analysed early signs of disease expression using available electrocardiography and cardiac magnetic resonance imaging data.ResultsWe found a prevalence of 1:578, 1:251 and 1:149 for pathogenic and likely pathogenic variants associated with ARVC, DCM and HCM respectively. Compared to controls, cardiovascular mortality was higher in DCM G+ (OR 1.67 [95% CI 1.04;2.59], p=0.030), but similar in ARVC and HCM G+ (p≥0.100). Cardiomyopathy or heart failure diagnosis were more frequent in DCM G+ (OR 3.66 [95% CI 2.24;5.81], p=4.9×10−7) and HCM G+ (OR 3.03 [95% CI 1.98;4.56], p=5.8×10−7), but comparable in ARVC G+ (p=0.172). In contrast, ARVC G+ had more ventricular arrhythmias (p=3.3×10−4). In undiagnosed individuals, left ventricular ejection fraction was reduced in DCM G+ (p=0.009).ConclusionsIn the general population, pathogenic and likely pathogenic variants associated with ARVC, DCM or HCM are not uncommon. Although G+ have increased mortality and morbidity, disease penetrance in these carriers from the general population remains low (1.2-3.1%). Follow-up decisions in case of incidental findings should not be based solely on a variant, but on multiple factors, including family history and disease expression.
Effect of Vaccination on Household Transmission of SARS-CoV-2 Delta VOC
Authors: Lyngse Frederik Plesner , Mølbak Kåre , Denwood Matt , Christiansen Lasse Engbo , Møller Camilla Holten , Rasmussen Morten , Cohen Arieh Sierrah , Stegger Marc , Fonager Jannik , Sieber Raphael , Ellegaard Kirsten , Nielsen Claus , Kirkeby Carsten Thure 
Published: January 2022

1AbstractThe SARS-CoV-2 Delta variant of concern (VOC), which has shown increased transmission compared with previous variants, emerged rapidly globally during the first half of 2021, and became one of the most widespread SARS-CoV-2 variants worldwide. We utilized total population data from 24,693 Danish households with 53,584 potential secondary cases to estimate household transmission of the Delta VOC in relation to vaccination status. We found that the vaccine effectiveness against susceptibility (VES) was 61% (95%-CI: 59-63) and that the vaccine effectiveness against transmissibility (VET) was 42% (95%-CI: 39-45). We also found that unvaccinated individuals with an infection exhibited a higher viral load (one third of a standard deviation) compared to fully vaccinated individuals with a breakthrough infection. Our results imply that vaccinations reduce susceptibility as well as transmissibility. The results are important for policy makers to select strategies for reducing transmission of SARS-CoV-2.
Persistence of endogenous SARS-CoV-2 and pepper mild mottle virus RNA in wastewater settled solids
Authors: Roldan-Hernandez Laura , Graham Katherine E. , Duong Dorothea , Boehm Alexandria B. 
Published: January 2022

AbstractLimited information is available on the decay rate of endogenous SARS-CoV-2 and pepper mild mottle virus (PMMoV) RNA in wastewater and primary settled solids, potentially limiting an understanding of how transit or holding times within wastewater infrastructure might impact RNA measurements and their relationship to community COVID-19 infections. In this study, primary settled solids samples were collected from two wastewater treatment plants in the San Francisco Bay Area. Samples were thoroughly mixed, aliquoted into subsamples, and stored at 4°C, 22°C, and 37 °C for 10 days. The concentration of SARS-CoV-2 (N1 and N2 targets) and PMMoV RNA was measured using an RT-ddPCR. Limited decay (< 1 log10 reduction) was observed in the detection of viral RNA targets at all temperature conditions, suggesting that SARS-CoV-2 and PMMoV RNA can be highly persistent in solids. First-order decay rate constants ranged from 0.011 - 0.098 day-1 for SARS-CoV-2 RNA and 0.010 - 0.091 day-1 for PMMoV RNA, depending on temperature conditions. Slower decay was observed for SARS-CoV-2 RNA in primary settled solids compared to previously reported decay in wastewater influent. Further research is needed to understand if solid content and wastewater characteristics might influence the persistence of viral RNA targets.SynopsisSARS-CoV-2 and PMMoV genomic RNA is highly stable in wastewater settled solids over 10 days at several environmentally relevant temperatures.Abstract Figure
RETINOBLASTOMA RELATED (RBR) interaction with key factors of the RNA-directed DNA methylation (RdDM) pathway
Authors: Jesús León-Ruiz , Annie Espinal-Centeno , Ikram Blilou , Ben Scheres , Mario Arteaga-Vázquez , Alfredo Cruz-Ramírez 
Published: January 2022

SummaryTransposable elements and other repetitive elements are silenced by the RNA-directed DNA methylation pathway (RdDM). In RdDM, POLIV-derived transcripts are converted into double stranded RNA (dsRNA) by the activity of RDR2 and subsequently processed into 24 nucleotide short interfering RNAs (24 -nt siRNAs) by DCL3. 24-nt siRNAs are recruited by AGO4 and serve as guides to direct AGO4 - siRNA complexes to chromatin bound POLV-derived transcripts generated from the template/target DNA. The interaction between POLV, AGO4, DMS3, DRD1, RDM1 and DRM2 promotes DRM2-mediated de novo DNA methylation.The Arabidopsis Retinoblastoma protein homolog is a master regulator of cell cycle, stem cell maintenance and development. In silico exploration of RBR protein partners revealed that several members of the RdDM pathway contain a motif that confers high affinity binding to RBR, including the largest subunits of POLIV and POLV (NRPD1 and NRPE1), the shared second largest subunit of POLIV and POLV (NRPD/E2), RDR1, RDR2, DCL3, DRM2 and SUVR2. We demonstrate that RBR binds to DRM2, DRD1 and SUVR2. We also report that seedlings from loss -of-function mutants in RdDM and in RBR show similar phenotypes in the root apical meristem. Furthermore, we show that RdDM and SUVR2 targets are up-regulated in the 35S::AmiGO-RBR background.Our results suggest a novel mechanism for RBR function in transcriptional gene silencing based on the interaction with key players of the RdDM pathway and opens several new hypotheses, including the convergence of RBR-DRM2 on the transcriptional control of TEs and several cell/tissue and stage -specific target genes.
Machine learning-assisted identification of factors contributing to the technical variability between bulk and single-cell RNA-seq experiments
Authors: Lipnitskaya Sofya , Shen Yang , Legewie Stefan , Klein Holger , Becker Kolja 
Published: January 2022

AbstractBackgroundRecent studies in the area of transcriptomics performed on single-cell and population levels reveal noticeable variability in gene expression measurements provided by different RNA sequencing technologies. Due to increased noise and complexity of single-cell RNA-Seq (scRNA-Seq) data over the bulk experiment, there is a substantial number of variably-expressed genes and so-called dropouts, challenging the subsequent computational analysis and potentially leading to false positive discoveries. In order to investigate factors affecting technical variability between RNA sequencing experiments of different technologies, we performed a systematic assessment of single-cell and bulk RNA-Seq data, which have undergone the same pre-processing and sample preparation procedures.ResultsOur analysis indicates that variability between gene expression measurements as well as dropout events are not exclusively caused by biological variability, low expression levels, or random variation. Furthermore, we propose FAVSeq, a machine learning-assisted pipeline for detection of factors contributing to gene expression variability in matched RNA-Seq data provided by two technologies. Based on the analysis of the matched bulk and single-cell dataset, we found the 3’-UTR and transcript lengths as the most relevant effectors of the observed variation between RNA-Seq experiments, while the same factors together with cellular compartments were shown to be associated with dropouts.ConclusionsHere, we investigated the sources of variation in RNA-Seq profiles of matched single-cell and bulk experiments. In addition, we proposed the FAVSeq pipeline for analyzing multimodal RNA sequencing data, which allowed to identify factors affecting quantitative difference in gene expression measurements as well as the presence of dropouts. Hereby, the derived knowledge can be employed further in order to improve the interpretation of RNA-Seq data and identify genes that can be affected by assay-based deviations. Source code is available under the MIT license at https://github.com/slipnitskaya/FAVSeq.
Reconstructing Kinetic Models for Dynamical Studies of Metabolism using Generative Adversarial Networks
Authors: Choudhury Subham , Moret Michael , Salvy Pierre , Weilandt Daniel , Hatzimanikatis Vassily , Miskovic Ljubisa 
Published: January 2022

AbstractKinetic models of metabolic networks relate metabolic fluxes, metabolite concentrations, and enzyme levels through well-defined mechanistic relations rendering them an essential tool for systems biology studies aiming to capture and understand the behavior of living organisms. However, due to the lack of information about the kinetic properties of enzymes and the uncertainties associated with available experimental data, traditional kinetic modeling approaches often yield only a few or no kinetic models with desirable dynamical properties making the computational analysis unreliable and computationally inefficient. We present REKINDLE (REconstruction of KINetic models using Deep LEarning), a deep-learning-based framework for efficiently generating large-scale kinetic models with dynamic properties matching the ones observed in living organisms. We showcase REKINDLE’s efficiency and capabilities through three studies where we: (i) generate large populations of kinetic models that allow reliablein silicotesting of hypotheses and systems biology designs, (ii) navigate the phenotypic space by leveraging the transfer learning capability of generative adversarial networks, demonstrating that the generators trained for one physiology can be fine-tuned for another physiology using a low amount of data, and (iii) expand upon existing datasets, making them amenable to thorough computational biology and data-science analyses. The results show that data-driven neural networks assimilate implicit kinetic knowledge and structure of metabolic networks and generate novel kinetic models with tailored properties and statistical diversity. We anticipate that our framework will advance our understanding of metabolism and accelerate future research in health, biotechnology, and systems and synthetic biology. REKINDLE is available as an open-access tool.
HIGH FREQUENCY ROOT DYNAMICS: SAMPLING AND INTERPRETATION USING REPLICATED ROBOTIC MINIRHIZOTRONS
Authors: Nair Richard , Strube Martin , Hertel Martin , Kolle Olaf , Rolo Victor , Migliavacca Mirco 
Published: January 2022

ABSTRACTAutomating dynamic fine root data collection in the field is a longstanding challenge with multiple applications for co-interpretation and synthesis for ecosystem understanding. High frequency root data are only achievable with paired automated sampling and processing. However, automatic minirhizotron (root camera) instruments are still rare and data is often not collected in natural soils nor analysed at high temporal resolution. Instruments must also be affordable for replication and robust under variable natural conditions.Here, we show a system built with off-the-shelf parts which samples at sub-daily resolution. We paired this with a neural network to analyse all images collected. We performed two mesocosm studies and two field trials alongside ancillary data collection (soil CO2efflux, temperature and moisture content, and ‘PhenoCam’-derived above-ground dynamics. We produce robust daily time-series of root dynamics under all conditions. Temporal root changes were a stronger driver than absolute biomass on soil CO2efflux in mesocosm. Proximal sensed above ground dynamics and belowground from minirhizotron data were not synchronised. Root properties extracted were sensitive to soil moisture and occasionally to time of day (potentially relating to soil moisture). This may only affect high frequency imagery and should be considered in interpreting such data.HIGHLIGHTCompletely automatic root dynamics with method transferrable between field settings.
Chromosome-scale assembly of the highly heterozygous genome of red clover (Trifolium pratense L.), an allogamous forage crop species
Authors: Bickhart Derek M. , Koch Lisa M. , Smith Timothy P.L. , Riday Heathcliffe , Sullivan Michael L. 
Published: January 2022

AbstractRed clover (Trifolium pratense L.) is used as a forage crop due to a variety of favorable traits relative to other crops. Improved varieties have been developed through conventional breeding approaches, but progress could be accelerated and gene discovery facilitated using modern genomic methods. Existing short-read based genome assemblies of the ~420 Megabase (Mb) genome are fragmented into >135,000 contigs with numerous errors in order and orientation within scaffolds, likely due to the biology of the plant which displays gametophytic self-incompatibility resulting in inherent high heterozygosity. A high-quality long-read based assembly of red clover is presented that reduces the number of contigs by more than 500-fold, improves the per-base quality, and increases the contig N50 statistic by three orders of magnitude. The 413.5 Mb assembly is nearly 20% longer than the 350 Mb short read assembly, closer to the predicted genome size. Quality measures are presented and full-length isoform sequence of RNA transcripts reported for use in assessing accuracy and for future annotation of the genome. The assembly accurately represents the seven main linkage groups present in the genome of an allogamous (outcrossing), highly heterozygous plant species.
Estimating dynamic individual coactivation patterns based on densely sampled resting-state fMRI data and utilizing it for better subject identification
Authors: Yang Hang , Yao Xing , Zhang Hong , Meng Chun , Biswal Bharat 
Published: January 2022

AbstractAs a complex dynamic system, the brain exhibits spatially organized recurring patterns of activity over time. Coactivation patterns (CAPs), which analyzes data from each single frame, has been utilized to detect transient brain activity states recently. However, previous CAP analyses have been conducted at the group-level, which might neglect meaningful individual differences. Here, we estimate individual CAP states at both subject- and scan-level based on a densely-sampled dataset: Midnight Scan Club. We used differential identifiability, which measures the gap between intra- and intersubject similarity, to evaluate individual differences. We found individual CAPs at the subject-level achieved the best discrimination ability by maintaining high intra-subject similarity and enlarging inter-subject differences, and brain regions of association networks mainly contributed to the identifiability. On the other hand, scan-level CAP states were unstable across scans for the same participant. Expectedly, we found subject-specific CAPs became more reliable and discriminative with more data (i.e., longer duration). As the acquisition time of each participant is limited in practice, our results recommend a data collection strategy that collects more scans with appropriate duration (e.g., 12~15 mins/scan) to obtain more reliable subject-specific CAPs, when total acquisition time is fixed (e.g., 150 mins). Overall, this work has constructed reliable subject-specific CAP states with meaningful individual differences and provides a starting point for the subsequent applications of individual brain dynamics.
Ghost lineages can invalidate or even reverse findings regarding gene flow
Authors: Tricou Théo , Tannier Eric , de Vienne Damien M. 
Published: January 2022

AbstractIntrogression, endosymbiosis and gene transfer, i.e. Horizontal Gene Flow (HGF), are primordial sources of innovation in all domains of life. Our knowledge on HGF relies on detection methods that exploit some of its signatures left on extant genomes. One of them is the effect of HGF on branch lengths of constructed phylogenies. This signature has been formalized in statistical tests for HGF detection, and used for example to detect massive adaptive gene flows in malaria vectors or to order evolutionary events involved in eukaryogenesis. However these studies rely on the assumption that ghost lineages (all unsampled extant and extinct taxa) have little influence. We demonstrate here with simulations and data re-analysis, that when considering the more realistic condition that unsampled taxa are legion compared to sampled ones, the conclusion of these studies become unfounded or even reversed. This illustrates the necessity to recognize the existence of ghosts in evolutionary studies.