bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long divergent haplotypes introgressed from wild sheep are associated with distinct morphological and adaptive characteristics in domestic sheep
Authors: Cheng Hong , Zhang Zhuangbiao , Wen Jiayue , Lenstra Johannes A. , Heller Rasmus , Cai Yudong , Guo Yingwei , Li Ming , Li Ran , Li Wenrong , He Sangang , Wang Jintao , Shao Junjie , Song Yuxuan , Zhang Lei , Billah Masum , Wang Xihong , Liu Mingjun , Jiang Yu 
Published: May 2022

AbstractThe worldwide sheep population comprises more than 1000 breeds. Together, these exhibit a considerable morphological diversity, which has not been extensively investigated at the molecular level. Here, we analyze whole-genome sequencing individuals of 1,098 domestic sheep from 154 breeds, and 69 wild sheep from seven Ovis species. On average, we detected 6.8%, 1.0% and 0.2% introgressed sequence in domestic sheep originating from Iranian mouflon, urial and argali, respectively, with rare introgressions from other wild species. Interestingly, several introgressed haplotypes contributed to the morphological differentiations across sheep breeds, such as a RXFP2 haplotype from Iranian mouflon conferring the spiral horn trait, a MSRB3 haplotype from argali strongly associated with ear morphology, and a VPS13B haplotype probably originating from urial and mouflon possibly associated with facial traits. Our results reveal that introgression events from wild Ovis species contributed to the high rate of morphological differentiation in sheep breeds, but also to individual variation within breeds. We propose that long divergent haplotypes are a ubiquitous source of phenotypic variation that allows adaptation to a variable environment, and that these remain intact in the receiving population due to reduced recombination.
The Proteomic Landscape of Genome-Wide Genetic Perturbations
Authors: Messner Christoph B. , Demichev Vadim , Muenzner Julia , Aulakh Simran , Röhl Annika , Herrera-Domínguez Lucía , Egger Anna-Sophia , Kamrad Stephan , Lemke Oliver , Calvani Enrica , Mülleder Michael , Lilley Kathryn S. , Kustatscher Georg , Ralser Markus 
Published: May 2022

SummaryFunctional genomic strategies help to address the genotype phenotype problem by annotating gene function and regulatory networks. Here, we demonstrate that combining functional genomics with proteomics uncovers general principles of protein expression, and provides new avenues to annotate protein function. We recorded precise proteomes for all non-essential gene knock-outs in Saccharomyces cerevisiae. We find that protein abundance is driven by a complex interplay of i) general biological properties, including translation rate, turnover, and copy number variations, and ii) their genetic, metabolic and physical interactions, including membership in protein complexes. We further show that combining genetic perturbation with proteomics provides complementary dimensions of functional annotation: proteomic profiling, reverse proteomic profiling, profile similarity and protein covariation analysis. Thus, our study generates a resource in which nine million protein quantities are linked to 79% of the yeast coding genome, and shows that functional proteomics reveals principles that govern protein expression.Highlights-Nine million protein quantities recorded in ~4,600 non-essential gene deletions in S. cerevisiae reveal principles of how the proteome responds to genetic perturbation-Genome-scale protein expression is determined by both functional relationships between proteins, as well as common biological responses-Broad protein expression profiles in slow-growing strains can be explained by chromosomal aneuploidies-Protein half-life and ribosome occupancy are predictable from protein abundance changes across knock-outs-Functional proteomics annotates missing gene function in four complementary dimensions
Identifying novel regulators of placental development using time series transcriptomic data and network analyses
Authors: Vu Ha T. H. , Kaur Haninder , Kies Kelby R. , Starks Rebekah R. , Tuteja Geetu 
Published: May 2022

AbstractThe placenta serves as a connection between the mother and the fetus during pregnancy, and provides the fetus with oxygen, nutrients, and growth hormones. However, the regulatory mechanisms and dynamic gene interaction networks underlying early placental development are understudied. Here, we generated RNA sequencing (RNA-seq) data from mouse fetal placenta tissues at embryonic day (e) 7.5, e8.5 and e9.5 to identify genes with timepoint-specific expression, then inferred gene interaction networks to analyze highly connected network modules. We determined that timepoint-specific gene network modules associated with distinct developmental processes, and with similar expression profiles to specific human placental cell populations. From each module, we obtained hub genes and their direct neighboring genes, which were predicted to govern placental functions. We confirmed that four novel candidate regulators identified through our analyses regulate cell migration in the HTR-8/SVneo cell line. Upon conclusion of this study, we were able to predict several novel regulators of placental development using network analysis of bulk RNA-seq data. Our findings and analysis approaches will be valuable for future studies investigating the transcriptional landscape of early placental development.
The Effects of Negative Periocular Pressure on Biomechanics of the Optic Nerve Head and Cornea: A Computational Modeling Study
Authors: Safa Babak N. , Bleeker Adam , Berdahl John P. , Ethier C. Ross 
Published: May 2022

AbstractPurposeTo evaluate the effects of negative periocular pressure (NPP), and concomitant intraocular pressure (IOP) lowering, on the biomechanics of the optic nerve head (ONH) and cornea.MethodsWe developed a validated finite element (FE) model of the eye to compute tissue biomechanical strains induced in response to NPP delivered using the Multi-Pressure Dial (MPD) system. The model was informed by clinical measurements of IOP lowering and was based on published tissue properties. We also conducted sensitivity analyses by changing pressure loads and tissue properties.ResultsApplication of -7.9 mmHg NPP decreased strain magnitudes in the ONH by c. 50% while increasing corneal strain magnitudes by c. 25%. Comparatively, a similar increase in corneal strain was predicted to occur due to an increase in IOP of 4 mmHg. Sensitivity studies indicated that NPP lowers strain in the ONH by reducing IOP and that these effects persisted over a range of tissue stiffnesses and spatial distributions of NPP.ConclusionsNPP is predicted to considerably decrease ONH strain magnitudes. It also increases corneal strain but to an extent expected to be clinically insignificant. Thus, using NPP to lower IOP and hence decrease ONH mechanical strain is likely biomechanically beneficial for glaucoma patients.Translational RelevanceThis study provides the first description of how NPP affects ONH biomechanics and explains the underlying mechanism of ONH strain reduction. It complements current empirical knowledge about the MPD system and guides future studies of NPP as a treatment for glaucoma.
Comparison of simple RNA extraction methods for molecular diagnosis of hepatitis C virus in plasma
Authors: Hongjaisee Sayamon , Jabjainai Yosita , Sakset Suthasinee , Preechasuth Kanya , Ngo-Giang-Huong Nicole , Khamduang Woottichai 
Published: May 2022

AbstractWe evaluated the efficacy of four simple RNA extraction methods for the detection of hepatitis C virus (HCV) in plasma samples: silica-membrane-based, magnetic beads-based, boiling with Diethyl Pyrocarbonate (DEPC)-treated distilled water or a commercial lysis buffer. HCV RNA was detected using both real time reverse transcription polymerase chain reaction (RT-PCR) and reverse transcription loop mediated isothermal amplification (RT-LAMP). The magnetic beads-based extraction can be used as an alternative RNA extraction method for on-site HCV detection. Boiling with DEPC-treated distilled water was not appropriate for low HCV load samples and boiling with a lysis buffer was not recommended.
Identification of Three Medically Important Mosquito Species Using Raman Spectroscopy
Authors: Omucheni Dickson L , Kaduki Kenneth A , Mukabana Wolfgang R 
Published: May 2022

AbstractAccurate identification of disease vector insects is crucial when collecting epidemiological data. Traditionally, mosquitoes that transmit diseases like malaria, yellow fever, chikungunya, and dengue fever have been identified by looking at their external morphological features at different life cycle stages. This process is tedious and labour intensive.In this paper, the potential of Raman spectroscopy in combination with Linear and Quadratic Discriminant Analysis to classify three mosquito species, namely:Aedes aegypti, Anopheles gambiaeandCulex quinquefasciatus, was explored. The classification was based on the mosquitoes’ cuticular melanin. The three mosquito species represented two subfamilies of medically important mosquitoes, i.e. the Anophelinae and the Culicinae. The housefly (Musca domestica) was included as a ‘control’ group to assess the discrimination ability of the classifiers. This study is the first to use Raman spectroscopy to classify mosquitoes. Fresh mosquitoes were anaesthetized with chloroform, and a dispersive Raman microscope was used to capture spectra from their legs. Broad melanin peaks centred around 1400 cm-1, 1590 cm-1, and 2060 cm-1dominated the spectra. Variance Threshold (VT) and Principal Component Analysis (PCA) were used for feature selection and feature extraction respectively from the preprocessed data. The extracted features were then used to train and test Linear Discriminant Analysis (LDA) and Quadratic Discriminant Analysis (QDA) classifiers.The VT/PCA/QDA classification model performed better than VT/PCA/LDA. VT/PCA/QDA achieved an overall accuracy of 94%, sensitivity of 87% and specificity of 96%, whereas VT/PCA/LDA attained an accuracy of 85%, a sensitivity of 69% and a specificity of 90%. The success of these relatively simple classification models on Raman spectroscopy data lays the groundwork for future development of models for discriminating morphologically indistinguishable insect species.
Long-term adaptation to galactose as a sole carbon source selects for mutations in nutrient signaling pathways
Authors: Martínez Artemiza A. , Conboy Andrew , Buskirk Sean W. , Marad Daniel A. , Lang Gregory I. 
Published: May 2022

ABSTRACTGalactose is a secondary fermentable sugar that requires specific regulatory and structural genes for its assimilation, which are under catabolite repression by glucose. When glucose is absent, the catabolic repression is attenuated, and the structuralGALgenes are fully activated. InSaccharomyces cerevisiae, theGALpathway is under selection in environments where galactose is present. However, it is unclear the adaptive strategies in response to long-term propagation in galactose as a sole carbon source in laboratory evolution experiments. Here, we performed a 4,000-generation evolution experiment using 48 diploidSaccharomyces cerevisiaepopulations to study adaptation in galactose. We show that fitness gains were greater in the galactose-evolved population than in identically evolved populations with glucose as a sole carbon source. Whole-genome sequencing of 96 evolved clones revealed recurrentde novosingle nucleotide mutations in candidate targets of selection, copy number variations, and ploidy changes. We find that most mutations that improve fitness in galactose lie outside of the canonicalGALpathway and are involved in nutrient signaling. Reconstruction of specific evolved alleles in candidate target of selection,SEC23andIRA1, showed a significant increase in fitness in galactose compared to glucose. In addition, most of our evolved populations (28/46; 61%) fixed aneuploidies on Chromosome VIII, suggesting a parallel adaptive amplification. Finally, we show greater loss of extrachromosomal elements in our glucose-evolved lineages compared with previous glucose evolution. Broadly, these data further our understanding of the evolutionary pressures that drive adaptation to less-preferred carbon sources.
Predictability shifts from local to global rules during bacterial adaptation
Authors: Couce Alejandro , Magnan Melanie , Lenski Richard E. , Tenaillon Olivier 
Published: May 2022

AbstractThe distribution of fitness effects of new mutations is central to predicting adaptive evolution, but observing how it changes as organisms adapt is challenging. Here we use saturated, genome-wide insertion libraries to quantify how the fitness effects of new mutations changed in twoE. colipopulations that adapted to a constant environment for 15,000 generations. The proportions of neutral and deleterious mutations remained constant, despite large fitness gains. In contrast, the beneficial fraction declined rapidly, approximating an exponential distribution, with strong epistasis profoundly changing the genetic identity of adaptive mutations. Despite this volatility, many important targets of selection were predictable from the ancestral distribution. This predictability occurs because genetic target size contributed to the fixation of beneficial mutations as much as or more than their effect sizes. Overall, our results demonstrate that short-term adaptation can be idiosyncratic but empirically predictable, and that long-term dynamics can be described by simple statistical principles.One-Sentence SummaryCouce et al. demonstrate that short-term bacterial adaptation is predictable at the scale of individual genes, while long-term adaptation is predictable at a global scale.
Improvement of sensory deficits in Fragile X mice by increasing cortical interneuron activity after the critical period
Authors: Kourdougli Nazim , Suresh Anand , Liu Benjamin , Juarez Pablo , Lin Ashley , Chung David T. , Graven Sams Anette , Gandal Michael , Martínez-Cerdeño Verónica , Buonomano Dean V. , Hall Benjamin J. , Mombereau Cédric , Portera-Cailliau Carlos 
Published: May 2022

SUMMARYChanges in the function of inhibitory interneurons (INs) during cortical development could contribute to the pathophysiology of neurodevelopmental disorders. Using all-optical in vivo approaches in postnatal mouse somatosensory cortex (S1), we find that parvalbumin (PV) IN precursors are hypoactive and decoupled from excitatory neurons in Fmr1−/− mice, a model of Fragile X Syndrome (FXS). This leads to a loss of PV-INs in both mice and humans with FXS. Increasing the activity of future PV-INs in neonatal Fmr1−/− mice restores PV density and ameliorates transcriptional dysregulation in S1, but not circuit dysfunction. Critically, administering a novel allosteric modulator of Kv3.1 channels after the S1 critical period does rescue circuit dynamics and tactile defensiveness. Symptoms in FXS and related disorders could be mitigated by targeting PV-INs.
Skewness in bee and flower phenological distributions
Authors: Stemkovski Michael , Dickson Rachel G. , Griffin Sean R. , Inouye Brian D. , Inouye David W. , Pardee Gabriella L. , Underwood Nora , Irwin Rebecca E. 
Published: May 2022

AbstractPhenological distributions are characterized by their central tendency, breadth, and shape, and all three determine the extent to which interacting species overlap in time. Pollination mutualisms rely on temporal co-occurrence of pollinators and their floral resources, and while much work has been done to characterize the shapes of flower phenological distributions, similar studies including pollinators are lacking. Here, we provide the first broad assessment of skewness, a component of distribution shape, for a bee community. We compare skewness in bees to that in flowers, related bee and flower skewness to other properties of their phenology, and quantify the potential consequences of differences in skewness between bees and flowers. Both bee and flower phenologies tend to be right-skewed, with a more exaggerated asymmetry in bees. Early-season species tend to be the most skewed, and this relationship is also stronger in bees than in flowers. Based on a simulation experiment, differences in bee and flower skewness could account for up to 14% of pair-wise overlap differences. Given the potential for interaction loss, we argue that difference in skewness of interacting species is an under-appreciated property of phenological change.
The Necrosis- and Ethylene-inducing peptide 1-like protein (NLP) gene family of the plant pathogen Corynespora cassiicola
Authors: Dal’Sasso Thaís Carolina da Silva , da Rocha Vinícius Delgado , Rody Hugo Vianna Silva , Costa Maximiller Dal-Bianco Lamas , de Oliveira Luiz Orlando 
Published: May 2022

ABSTRACTEffectors are secreted by plant-associated microorganisms in order to modify the host cell physiology. As effectors, the Necrosis- and Ethylene-inducing peptide 1-like proteins (NLPs) are involded in the early phases of plant infection and may trigger host immune responses. Corynespora cassiicola is a polyphagous plant-pathogen that causes target spot on many agriculturally important crops. Using genome assembly, gene prediction, and proteome annotation tools, we retrieved 135 NLP-encoding genes from proteomes of 44 isolates. We explored the evolutionary history of NLPs using Bayesian phylogeny, gene genealogies, and selection analyses. We accessed the expression profiles of the NLP genes during the early phase of C. cassiicola–soybean interaction. Three NLP effector genes (Cc_NLP1.1, Cc_NLP1.2A, and Cc_NLP1.2B) were maintained in the genomes of all isolates tested. A non-effector NLP gene (Cc_NLP1.3) was found in three isolates that had been originally obtained from soybean. NLP effectors were under different selective constraints: Cc_NLP1.1 was under stronger selective pressure, while Cc_NLP1.2A was under a more relaxed constraint. Meanwhile, Cc_NLP1.2B likely evolved under either positive or balancing selection. Despite highly divergent, the effector NLPs maintain conserved the residues necessary to trigger plant immune responses, suggesting they are potentially functional. Only the Cc_NLP1.1 effector gene was significantly expressed at the early hours of soybean colonization, while Cc_NLP1.2A and Cc_NLP1.2B showed much lower levels of gene expression.
Simulations of Pathogenic E1α Variants: Allostery and Impact on Pyruvate Dehydrogenase Complex-E1 Structure and Function
Authors: Gokcan Hatice , Bedoyan Jirair K. , Isayev Olexandr 
Published: May 2022

ABSTRACTPyruvate dehydrogenase complex (PDC) deficiency is a major cause of primary lactic acidemia resulting in high morbidity and mortality, with limited therapeutic options. The E1 component of the mitochondrial multienzyme PDC (PDC-E1) is a symmetric dimer of heterodimers (αβ/α’β’) encoded by the PDHA1 and PDHB genes, with two symmetric active sites each consisting of highly conserved phosphorylation loops A and B. PDHA1 mutations are responsible for 82-88% of cases. Greater than 85% of E1α residues with disease-causing missense mutations (DMMs) are solvent inaccessible, with ~30% among those involved in subunit-subunit interface contact (SSIC). We performed molecular dynamics simulations of wild-type (WT) PDC-E1 and E1 variants with E1α DMMs at R349 and W185 (residues involved in SSIC), to investigate their impact on human PDC-E1 structure. We evaluated the change in E1 structure and dynamics and examined their implications on E1 function with the specific DMMs. We found that the dynamics of phosphorylation Loop A which is crucial for E1 biological activity, changes with DMMs that are at least about 15 Å away. Because communication is essential for PDC-E1 activity (with alternating active sites), we also investigated the possible communication network within WT PDC-E1 via centrality analysis. We observed that DMMs altered/disrupted the communication network of PDC-E1. Collectively, these results indicate allosteric effect in PDC-E1, with implications for development of novel small molecule therapeutics for specific recurrent E1α DMMs such as replacements of R349 responsible for ~10% of PDC deficiency due to E1α DMMs.
COVID-19 lockdown reveals fish density may be much higher in marine reserves
Authors: Olán-González Manuel , Reyes-Bonilla Héctor , Arreola-Alarcon Isabel Montserrat , Uribe Regina Valdovinos , Olivier Damien 
Published: May 2022

AbstractMarine reserves generally allow ecotourism to offer an alternative income to fishing. However, we need to assess its impact on wildlife to make this activity sustainable. The COVID-19 lockdown provided a unique opportunity to evaluate wildlife diversity in the absence of human activity. In a Mexican reserve, we monitored fish assemblages before, during, and just after the lockdown. We show that ecotourism activities alter the behavior of fishes by finding a 2.5-fold density rise during the lockdown. We suggest that the noise pollution generated by the numerous recreational vessels is a significant factor of perturbation. In the absence of noise pollution, some fishes may be bolder (less hidden) and others can come back to the reserve from usually quieter areas (e.g., deeper waters). Our results represent a great worldwide incentive to improve the health of marine reserves by establishing concrete measures in managing plans to mitigate noise pollution.Open Research statementAll data and code necessary to reproduce the results of the paper are enclosed in the submission for review purposes, and will be published on Zenodo following the acceptance of the paper.
Voltage-Dependent Ca2+ Release Is Impaired in Hypokalemic Periodic Paralysis Caused by CaV1.1-R528H but not by NaV1.4-R669H
Authors: DiFranco Marino , Cannon Stephen C. 
Published: May 2022

ABSTRACTHypokalemic periodic paralysis (HypoPP) is a channelopathy of skeletal muscle caused by missense mutations in the voltage sensor domains (usually at an arginine of the S4 segment) of the CaV1.1 calcium channel or of the NaV1.4 sodium channel. The primary clinical manifestation is recurrent attacks of weakness, resulting from impaired excitability of anomalously depolarized fibers containing leaky mutant channels. While the ictal loss of fiber excitability is sufficient to explain the acute episodes of weakness, a deleterious change in voltage sensor function for CaV1.1 mutant channels may also compromise excitation-contraction coupling (EC-coupling).We used the low-affinity Ca2+ indicator OGN-5 to assess voltage-dependent Ca2+-release as a measure of EC-coupling for our knock-in mutant mouse models of HypoPP. The peak ΔF/F0 in fibers isolated from CaV1.1-R528H mice was about two-thirds of the amplitude observed in WT mice; whereas in HypoPP fibers from NaV1.4-R669H mice the ΔF/F0 was indistinguishable from WT. No difference in the voltage dependence of ΔF/F0 from WT was observed for fibers from either HypoPP mouse model. Because late-onset permanent muscle weakness is more severe for CaV1.1-associated HypoPP than for NaV1.4, we propose the reduced Ca2+-release for CaV1.1-R528H mutant channels may increase the susceptibility to fixed myopathic weakness. In contrast the episodes of transient weakness are similar for CaV1.1- and NaV1.4-associated HypoPP, consistent with the notion that acute attacks of weakness are primarily caused by leaky channels and are not a consequence of reduced Ca2+-release.