bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolution of recombination in self-fertilizing organisms
Authors: Stetsenko Roman , Roze Denis 
Published: February 2022

ABSTRACTCytological data from flowering plants suggest that the evolution of recombination rates is affected by the mating system of organisms, as higher chiasma frequencies are often observed in self-fertilizing species compared with their outcrossing relatives. Understanding the evolutionary cause of this effect is of particular interest, as it may shed light on the selective forces favoring recombination in natural populations. While previous models showed that inbreeding may have important effects on selection for recombination, existing analytical treatments are restricted to the case of loosely linked loci and weak selfing rates, and ignore the effect of genetic interference (Hill-Robertson effect), known to be an important component of selection for recombination in randomly mating populations. In this article, we derive general expressions quantifying the stochastic and deterministic components of selection acting on a mutation affecting the genetic map length of a whole chromosome along which deleterious mutations occur, valid for arbitrary selfing rates. The results show that selfing generally increases selection for recombination caused by interference among mutations as long as selection against deleterious alleles is sufficiently weak. While interference is often the main driver of selection for recombination under tight linkage or high selfing rates, deterministic effects can play a stronger role under intermediate selfing rates and high recombination, selecting against recombination in the absence of epistasis, but favoring recombination when epistasis is negative. Individual-based simulation results indicate that our analytical model often provides accurate predictions for the strength of selection on recombination under partial selfing.
Western diet unmasks transient low-level vinyl chloride exposure-induced tumorigenesis; potential role of the (epi-)transcriptome
Authors: Liu Silvia , He Liqing , Bannister Olivia B , Schnegelberger Regina D , Tao Junyan , Althouse Andrew D , Schopfer Francisco J , Wahlang Banrida , Cave Matthew C , Monga Satdarshan P , Zhang Xiang , Arteel Gavin E , Beier Juliane I 
Published: February 2022

AbstractBackground & AimsVinyl chloride (VC) monomer is a volatile organic compound commonly used in industry to produce polyvinyl chloride (PVC). At high exposure levels, VC causes liver cancer and toxicant-associated steatohepatitis. However, lower exposure levels (i.e., < regulatory exposure limits) that do not directly damage the liver, enhance injury caused by Western diet (WD). Although these lower exposure levels are considered ‘safe,’ it is unknown if the long-term impact of transient low-concentration VC enhances the risk of liver cancer development. Low-concentration VC is especially a concern given that fatty liver disease is in and of itself a risk factor for the development of liver cancer.MethodsC57Bl/6J mice were fed WD or control diet (CD) for 1 year. During the first 12 weeks of feeding only, mice were also exposed to VC via inhalation at sub-regulatory limit concentrations (<1 ppm) or air for 6 hours/day, 5 days/week.ResultsFeeding WD for 1 year caused significant hepatic injury, including steatohepatitis and moderate fibrosis, which was exacerbated by VC. Additionally, VC increased the number of tumors which ranged from moderately to poorly differentiated hepatocellular carcinoma (HCC). Transcriptomic analysis demonstrated VC-induced changes in metabolic but also ribosomal processes. Epitranscriptomic analysis showed a VC-induced shift of the modification pattern that has been associated with metabolic disease, mitochondrial dysfunction, and cancer.ConclusionsThese data indicate that VC sensitizes the liver to other stressors (e.g., WD), resulting in enhanced tumorigenesis. These data raise concerns about a potential interaction between VC exposure and WD. Furthermore, it also emphasizes that current safety restrictions may be insufficient to account for other factors that can influence hepatotoxicity.
StabMap: Mosaic single cell data integration using non-overlapping features
Authors: Ghazanfar Shila , Guibentif Carolina , Marioni John C. 
Published: February 2022

ABSTRACTCurrently available single cell -omics technologies capture many unique features with different biological information content. Data integration aims to place cells, captured with different technologies, onto a common embedding to facilitate downstream analytical tasks. Current horizontal data integration techniques use a set of common features, thereby ignoring non-overlapping features and losing information. Here we introduce StabMap, a mosaic data integration technique that stabilises mapping of single cell data by exploiting the non-overlapping features. StabMap is a flexible approach that first infers a mosaic data topology, then projects all cells onto supervised or unsupervised reference coordinates by traversing shortest paths along the topology. We show that StabMap performs well in various simulation contexts, facilitates disjoint mosaic data integration, and enables the use of novel spatial gene expression features for mapping dissociated single cell data onto a spatial transcriptomic reference.
An inosine triphosphate pyrophosphatase safeguards plant nucleic acids from aberrant purine nucleotides
Authors: Straube Henryk , Straube Jannis , Rinne Jannis , Niehaus Markus , Witte Claus-Peter , Herde Marco 
Published: February 2022

SUMMARY-In plants, inosine is enzymatically introduced in some tRNAs but not in other RNAs or DNA. Nonetheless, our data show that RNA and DNA fromArabidopsis thalianacontain (deoxy)inosine, probably derived from non-enzymatic adenosine deamination in nucleic acids and usage of (deoxy)inosine triphosphate (dITP and ITP) during nucleic acid synthesis.-We combined biochemical approaches, sample preparation and LC-MS, as well as RNA-Seq to characterize a plant INOSINE TRIPHOSPHATE PYROPHOSPHATASE (ITPA) fromArabidopsis thaliana, which is conserved in many organisms, and investigated the sources of deaminated purine nucleotides in plants.-ITPA dephosphorylates deaminated nucleoside di- and triphosphates to the respective monophosphates.ITPAloss-of-function causes inosine di- and triphosphate accumulationin vivoand an elevated (deoxy)inosine content in DNA and RNA, as well as salicylic acid (SA) accumulation, early senescence and upregulation of transcripts associated with immunity and senescence. Cadmium-induced oxidative stress leads to more ITP in the wildtype, and this effect is enhanced initpamutants, suggesting that ITP originates from ATP deamination.-ITPA is part of a molecular protection system, preventing accumulation of (d)ITP, its usage for nucleic acid synthesis, and probably nucleic acid stress leading to SA accumulation, stress gene induction and early senescence.
Brevican, Neurocan, Tenascin-C and Tenascin-R Act as Important Regulators of the Interplay between Perineuronal Nets, Synaptic Integrity, Inhibitory Interneurons and Otx2
Authors: Mueller-Buehl Cornelius , Reinhard Jacqueline , Roll Lars , Bader Verian , Winklhofer Konstanze F. , Faissner Andreas 
Published: February 2022

AbstractFast-spiking parvalbumin interneurons are critical for the function of mature cortical inhibitory circuits. Most of these neurons are enwrapped by a specialized extracellular matrix structure (ECM) called perineuronal net (PNN), which can regulate their synaptic input. In this study, we investigated the relationship between PNNs, parvalbumin interneurons and synaptic distribution on these cells in the adult primary visual cortex (V1) of quadruple knockout mice deficient for the ECM molecules brevican, neurocan, tenascin-C and tenascin-R. We used super-resolution structured illumination microscopy (SIM) to analyze PNN structure and associated synapses. Additionally, we examined parvalbumin and calretinin interneuron populations. We observed a reduction in the number of PNN-enwrapped cells and a clear disorganization of the PNN structure in the quadruple knockout V1. This was accompanied by an imbalance of inhibitory and excitatory synapses with a reduction of inhibitory and an increase of excitatory synaptic elements along the PNNs. Also, the number of parvalbumin interneurons was reduced in the quadruple knockout, while calretinin interneurons, which do not wear PNNs did not display differences in number. Interestingly, we found the transcription factor Otx2 homeoprotein positive cell population also reduced. Otx2 is crucial for parvalbumin and PNN maturation and a positive feedback loop between these parameters has been described. Collectively, these data indicate an important role of brevican, neurocan, tenascin-C and tenascin-R in regulating the interplay between PNNs, inhibitory interneurons, synaptic distribution as well as Otx2 in the V1.
Expanding the pulse-reserve paradigm to microorganisms on the basis of differential reserve management strategies
Authors: Garcia-Pichel Ferran , Sala Osvaldo 
Published: February 2022

AbstractThe pulse-reserve paradigm (PRP) is central in dryland ecology, although traits of microorganisms were not explicitly considered in its inception. We asked if the PRP could be reframed to encompass organisms both large and small. We used a synthetic review of recent advances in arid land microbial autoecology combined with a mathematically explicit theoretical model. Preserving the PRPs original core of adaptations by reserve building, the model considers differential organismal strategies to manage these reserves. It proposes a gradient of organisms according to their reserve strategies, from nimble responders (NIRs) to torpid responders (TORs). It predicts how organismal fitness depends on pulse regimes and reserve strategies thus explaining organismal diversification and distribution. After accounting for scaling phenomena and redefining the microscale meaning of aridity, it becomes patent that the PRP is applicable to microbes, and that this modified PRP represents an inclusive theoretical framework working across life-forms.
Cortical compensation for afferent loss in older adults: Associations with GABA and speech recognition in noise
Authors: Harris Kelly C. , Balken Brendan , Dias James W. , McClaskey Carolyn M. , Rumschlag Jeffrey , Prisciandaro James , Dubno Judy R. 
Published: February 2022

AbstractAge-related deficits in auditory nerve (AN) function reduce afferent input to the auditory cortex. The extent to which the auditory cortex in older adults compensates for this loss of afferent input, also known as central gain, and the mechanisms underlying this compensation are not well understood. We took a neural systems approach to estimate central gain, measuring AN and cortical evoked responses within 50 older and 27 younger adults. Amplitudes were significantly smaller for older than for younger adults for AN responses but not for cortical responses. We used the relationship between AN and cortical response amplitudes in younger adults to predict cortical response amplitudes for older adults from their AN responses. Central gain in older adults was thus defined as the difference between their observed cortical responses and those predicted from the parameter estimates of younger adults. More central gain was associated with decreased cortical levels of GABA measured with 1H-MRS and poorer speech recognition in noise (SIN). Effects of central gain and GABA on SIN occur in addition to, and independent from, effects attributed to elevated hearing thresholds. Our results are consistent with animal models of central gain and suggest that reduced AN afferent input in some older adults may result in changes in cortical encoding and inhibitory neurotransmission, which contribute to reduced SIN. An advancement in our understanding of the changes that occur throughout the auditory system in response to the gradual loss of input with increasing age may provide potential therapeutic targets for intervention.SignificanceAge-related hearing loss is one of the most common chronic conditions of aging, yet little is known about how the cortex compensates for this loss of sensory input. We measured AN and cortical responses to the same stimulus in younger and older adults. In older adults we found an increase in cortical activity following concomitant declines in afferent input that are consistent with central gain. Increased central gain was associated with lower levels of cortical GABA, an inhibitory neurotransmitter, which predicted poorer speech recognition in noise. The results suggest that the cortex in older adults can compensate for attenuated sensory input by reducing inhibition to amplify the cortical response, but this amplification may lead to poorer speech recognition in noise.
Quality assessment and refinement of chromatin accessibility data using a sequence-based predictive model
Authors: Han Seong Kyu , Muto Yoshiharu , Wilson Parker C. , Chakravarti Aravinda , Humphreys Benjamin D. , Sampson Matthew G. , Lee Dongwon 
Published: February 2022

AbstractChromatin accessibility assays are central to the genome-wide identification of gene regulatory elements associated with transcriptional regulation. However, the data have highly variable quality arising from several biological and technical factors. To surmount this problem, we use the predictability of open-chromatin peaks from DNA sequence-based machine-learning models to evaluate and refine chromatin accessibility data. Our framework, gapped k-mer SVM quality check (gkmQC), provides the quality metrics for a sample based on the prediction accuracy of the trained models. We tested 886 samples with DNase-seq from the ENCODE/Roadmap projects to demonstrate that gkmQC can effectively identify high-quality samples underperforming owing to marginal read depths. Peaks identified in high-quality samples by gkmQC are more accurately aligned at functional regulatory elements, show greater enrichment of regulatory elements harboring functional variants from genome-wide association studies (GWAS), and explain greater heritability of phenotypes from their relevant tissues. Moreover, gkmQC can optimize the peak-calling threshold to identify additional peaks, especially for single-cell chromatin accessibility data as well as bulk data. Here we provide a standalone open-source toolkit (https://github.com/Dongwon-Lee/gkmQC) for such analyses and share improved regulatory maps using gkmQC. These resources will contribute to the functional interpretation of disease-associated regulatory genetic variation.
FtsH Protease Inactivation Allows Accumulation of Aberrant Photosystem II in a Chlamydomonas Rubredoxin Mutant
Authors: Calderon Robert H. , de Vitry Catherine , Wollman Francis-André , Niyogi Krishna K. 
Published: February 2022

AbstractThe assembly of photosystem II (PSII) requires the participation of assembly proteins that facilitate the step-wise association of its protein and pigment components into a functional complex capable of oxidizing water and reducing plastoquinone. We previously identified one such factor, the membrane-bound rubredoxin RBD1, but its precise role remains unknown in part due to the inability of the 2pac mutant strain of Chlamydomonas reinhardtii, which lacks RBD1, to accumulate PSII. Here, we show that decreased PSII accumulation in 2pac is due to increased proteolytic degradation. Inactivating the thylakoid membrane FtsH protease in the 2pac mutant background led to an increase in the abundance of PSII subunits and their integration into higher molecular weight complexes, including PSII dimers, capable of sustaining photoautotrophic growth. Dark- and low light-grown 2pac ftsh1-1 both accumulated a 23-kD fragment of the D1 protein, a marker typically associated with structural changes resulting from photodamage or photoinhibition. We introduced a HIS-tagged version of the PsbH protein into the 2pac ftsh1-1 background to purify and examine PSII. We found no detectable changes with respect to cofactor composition relative to the wild-type, leading to us to propose a model in which RBD1 promotes the proper folding of D1, possibly via delivery or reduction of the non-heme iron during PSII assembly. Our results demonstrate that introduction of the ftsh1-1 mutation into mutants defective in the biogenesis of thylakoid membrane complexes can allow for the accumulation and study of aberrant complexes that would otherwise be degraded due to their high protease sensitivity.
Structure of IgG-Fc hexamer reveals a mutual lock-and-key mode of Fc-Fc interaction
Authors: Yuan Daopeng , Zhou Shuaixiang , Ni Haiqing , Yang Weixin , Fang Xiao , Gao Yarong , Shao Zhiyuan , Bai Dongmei , Wu Zhihai , Zou Jia , Liu Lu , Shi Jiahui , Zheng Nan , Yu Michael , Liu Yongjun , Xiao Xiaodong , Chen Bingliang , Gao Changshou 
Published: February 2022

AbstractIgG exists mainly as monomer, but recent studies suggest that IgG forms hexamer to mediate antibody functions. Although many structures of IgG monomer and its fragments are determined, there is no IgG hexamer structure at atomic level due to the weak Fc-Fc interactions. Here we engineered a hexameric IgG with IgM tailpiece fusion and determined the structure by cryo-EM. IgG-Fc hexamer forms hexagon symmetry with the six Fcs lie in a plane with Fc-Fc interaction in a mutual lock-and-key mode. This structure provides structural insights into Fc-Fc interaction of IgG and reveals molecular basis for its function.
GIFT: New method for the genetic analysis of small gene effects involving small sample sizes
Authors: Rauch Cyril , Kyratzi Panagiota , Blott Sarah , Bray Sian , Wattis Jonathan 
Published: February 2022

AbstractSmall gene effects involved in complex/omnigenic traits remain costly to analyse using current genome-wide association methods (GWAS) because of the number of individuals required to return meaningful association(s), a.k.a. study power. Inspired by field theory in physics, we provide a different method called Genomic Informational Field Theory (GIFT). In contrast to GWAS, GIFT assumes that the phenotype is measured precisely enough and/or the number of individuals in the population is too small to permit the creation of categories. To extract information, GIFT uses the information contained in the cumulative sums difference of gene microstates between two configurations: (i) when the individuals are taken at random without information on phenotype values, and (ii) when individuals are ranked as a function of their phenotypic value. The difference in the cumulative sum is then attributed to the emergence of phenotypic fields. We demonstrate that GIFT recovers GWAS, that is, Fisher’s theory, when the phenotypic fields are linear (first order). However, unlike GWAS, GIFT demonstrates how the variance of microstate distribution density functions can also be involved in genotype-phenotype associations when the phenotypic fields are quadratic (second order). Using genotype-phenotype simulations based on Fisher’s theory as a toy model, we illustrate the application of the method with a small sample size of 1000 individuals.
IRE1 RNase controls CD95-mediated cell death
Authors: Pelizzari-Raymundo D , Pineau R , Papaioannou A , Zhou XC , Martin S , Avril T , Le Gallo M , Chevet E , Lafont E 
Published: February 2022

AbstractSignalling by the Unfolded Protein Response (UPR) or by the Death Receptors (DR) represents cellular stress pathways frequently activated towards pro-tumoral outputs in cancer. Experimental evidence has highlighted functional links between the UPR and the DR TRAIL-R1/2. Herein, we demonstrate that the UPR sensor IRE1 controls the expression of CD95/Fas, another DR, and its cell death-inducing ability. Whereas CD95 is not a general determinant of ER stress-induced cell death, IRE1 RNase activity inhibition increased CD95 expression and exacerbated CD95L-induced cell death in glioblastoma (GB) and Triple-Negative Breast Cancer (TNBC) cell lines. In accordance, CD95 mRNA was identified as a target of Regulated IRE1-Dependent Decay of RNA (RIDD). Moreover, CD95 expression is elevated in TNBC and GB human tumours exhibiting low RIDD activity. Surprisingly, CD95 expression is also lower in XBP1s-low human tumour samples. We show that IRE1 RNase inhibition led to CD95 expression attenuation and reduced CD95-mediated hepatic toxicity in mice. In addition, overexpression of XBP1s increased CD95 expression and sensitized GB and TNBC cells to CD95L-induced cell death. Overall, these results demonstrate the tight IRE1-mediated control of CD95-dependent cell death signals in a dual manner through both RIDD and XBP1s, and they identify a novel, pharmacologically actionable link between IRE1 and CD95 signalling.
Congenital Rift Valley fever in Sprague Dawley rats is associated with diffuse infection and pathology of the placenta
Authors: McMillen Cynthia M. , Boyles Devin A. , Kostadinov Stefan G. , Hoehl Ryan M. , Schwarz Madeline M. , Albe Joseph R. , Demers Matthew J. , Hartman Amy L. 
Published: February 2022

AbstractRift Valley fever (RVF) is a disease of animals and humans associated with abortions in ruminants and, more recently, late-gestation miscarriages in African women. Here, we use a rat model of congenital RVF to identify cellular tropism, pathology, and local immune responses occurring in the placenta during vertical transmission. Infection of pregnant rats during late gestation (embryonic day 14) resulted in vertical transmission to the placenta and widespread viral infection throughout the decidua, basal zone, and labyrinth zone. Some pups delivered from infected dams appeared normal while others had gross signs of teratogenicity including fetal death. Histopathological lesions were detected in placenta from pups regardless of teratogenicity, while teratogenic pups had more widespread hemorrhage throughout multiple placenta layers. Teratogenic events were also associated with significant increases in pro-inflammatory cytokines, type I interferons, and chemokines within the placental tissue. Thus, we found that RVFV displays a high degree of tropism for all placental tissue layers, and that the degree of hemorrhage and inflammatory mediator production is highest in placenta from pups with adverse outcomes. This is the first detailed pathological study of the mechanisms of RVFV infection of placental tissue in a tractable rodent model of congenital RVF disease.