bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing acute IOP-induced lamina cribrosa deformations pre-mortem and post-mortem
Authors: Wei Junchao , Hua Yi , Yang Bin , Wang Bo , Schmitt Samantha E. , Wang Bingrui , Lucy Katie A. , Ishikawa Hiroshi , Schuman Joel S. , Smith Matthew A. , Wollstein Gadi , Sigal Ian A. 
Published: September 2022

AbstractPurposeLamina cribrosa (LC) deformations caused by elevated intraocular pressure (IOP) are believed to contribute to glaucomatous neuropathy and have therefore been extensively studied, in many conditions from in-vivo to ex-vivo. We compare acute IOP-induced global and local LC deformations immediately before (pre-mortem) and after (post-mortem) sacrifice by exsanguination.MethodsThe optic nerve heads of three healthy monkeys 12-15 years old were imaged with spectral-domain optical coherence tomography under controlled IOP pre-mortem and post-mortem. Volume scans were acquired at baseline IOP (8-10 mmHg) and at 15, 30, and 40 mmHg IOP. A digital volume correlation technique was used to determine the IOP-induced 3D LC deformations (strains) in regions visible pre-mortem and post-mortem.ResultsBoth conditions exhibited similar nonlinear relationships between IOP increases and LC deformations. Median effective and shear strains were, on average over all eyes and pressures, smaller post-mortem than pre-mortem, by 14% and 11%, respectively (P’s < 0.001). Locally, however, the differences in LC deformation between conditions were variable. Some regions were subjected pre-mortem to triple the strains observed post-mortem, and others suffered smaller deformations pre-mortem than post-mortem.ConclusionsIncreasing IOP acutely caused nonlinear LC deformations with an overall smaller effect post-mortem than pre-mortem. Locally, deformations pre-mortem and post-mortem were sometimes substantially different. We suggest that the differences may be due to weakened mechanical support from the unpressurized central retinal vessels post-mortem.Translational RelevanceAdditional to the important pre-mortem information, comparison with post-mortem provides a unique context essential to understand the translational relevance of all post-mortem biomechanics literature.PrecisThe authors compared in monkeys acute IOP-induced deformations of the lamina cribrosa pre-mortem and post-mortem. Deformation trends were similar pre-mortem and post-mortem, but deformations pre-mortem were generally smaller than those post-mortem, with substantial local variations. The differences are likely due to loss of vessel support post-mortem.
The Molecular Mechanism of Chloramphenicol and Thiamphenicol Resistance Mediated by a Novel Oxidase CmO in Sphingomonadaceae
Authors: Ma Xiaodan , Zhang Liying , Ren Yijun , Yun Hui , Cui Hanlin , Li Qian , Guo Yuanqiang , Gao Shuhong , Zhang Fengliang , Wang Aijie , Liang Bin 
Published: September 2022

AbstractAntibiotic resistance mediated by bacterial enzyme inactivation plays a mysterious and crucial role for antibiotic degradation and selection pressure reduction in the environment. The enzymatic inactivation of the antibiotic chloramphenicol (CAP) involves nitro reduction, amide bond hydrolysis and acetylation modification. However, the molecular mechanism of enzymatic oxidation of CAP remains unknown. Here, a novel oxidase gene cmO was identified and confirmed biochemically to catalyze the resistance process through the oxidative inactivation at the side chain C-3’ position of CAP and thiamphenicol (TAP) in Sphingomonadaceae. The oxidase CmO is highly conservative in Sphingomonadaceae and shares the highest amino acid homology of 41.05% with the biochemically identified glucose methanol choline (GMC) oxidoreductases. Molecular docking and site-directed mutagenesis analyses demonstrated that CAP was anchored inside the protein pocket of CmO with the hydrogen bonding of key residues glycine (G)99, asparagine (N)518, methionine (M)474 and tyrosine (Y)380. CAP sensitivity test demonstrated that the acetyltransferase and CmO showed higher resistance to CAP as compared with the amide bond-hydrolyzing esterase and nitroreductase. This study provides a better theoretical basis and a novel diagnostic gene for understanding and assessing the fate and resistance risk of CAP and TAP in the environment.ImportanceRising levels of antibiotic resistance undermines ecological and human health as a result of indiscriminate usage of antibiotics. Various resistance mechanisms have been revealed, for instance genes encoding proteins that degrade antibiotics, yet requiring further exploration. In this study, we reported a novel gene encoding an oxidase involved in the inactivation of typical amphenicol antibiotics (chloramphenicol and thiamphenicol), and the molecular mechanism was elucidated. The observation provides novel data to understand capabilities of bacteria to tackle antibiotic stress and suggests complex function of enzymes in the context of antibiotic resistance development and antibiotics removal. The reported gene can be further employed as an indicator to monitor amphenicols fate in the environment, benefiting the risk assessment in this era of antibiotic resistance.
HDAC7 controls anti-viral and anti-tumor immunity by CD8+ T cells
Authors: Yerinde Cansu , Keye Jacqueline , Durlanik Sibel , Freise Inka , Nowak Franziska , Hsiao Hsiang-Jung , Letizia Marilena , Schlickeiser Stephan , Obermayer Benedikt , Huck Adrian , Friedrich Marie , Wu Hao , Kunkel Désirée , Kühl Anja A. , Bauer Sebastian , Thiel Andreas , Siegmund Britta , Glauben Rainer , Weidinger Carl 
Published: September 2022

AbstractClass II histone deacetylases (HDAC) orchestrate T cell-dependent immune responses via the epigenetic control of genes and via the post-translational modification of cytoplasmic and nuclear proteins. However, the contribution of single HDAC family members to the differentiation and function of peripheral CD8+ T cells remains elusive. We here demonstrate that HDAC7-deficiency leads to the upregulation of immune checkpoint molecules, decreased calcium influx as well as increased apoptosis of peripheral murine CD8+ T cells, which we could link to a MEF2D-dependent induction of FasL expression ultimately deterring the survival of HDAC7-deficient CD8+ T cells. Likewise, we observed in mouse models of lymphoma, that mice with a T cell specific-deletion of Hdac7 harbor impaired anti-tumor immune responses in syngeneic transfer models of lymphoma and we found that HDAC7 is required for CD8+ T cell-dependent memory recall responses in models of lymphocytic choriomeningitis virus infection. Taken together, we identify HDAC7 as a central regulator of cellular exhaustion and apoptosis of peripheral CD8+ T cells, controlling CD8+ T cell dependent anti-tumor and anti-viral immunity in mice.SignificanceAlthough HDAC7 was identified as an important regulator of thymocyte development and survival, its role in the homeostasis and the functions of adult CD8+ T cells is not fully understood. Here, we identify HDAC7 as a critical regulator of peripheral CD8+ T cells since its deletion impairs anti-tumor and anti-viral immune responses in mouse models of LCMV infection and transfer models of lymphoma. We attribute this phenotype to impaired survival, calcium homeostasis as well as deterred memory function and increased exhaustion of HDAC7-deficient CD8+ T cells. Our findings are of clinical relevance regarding potential immune suppressive side effects of HDAC inhibitors that are currently under clinical trials for the treatment of autoimmune diseases and cancers.
Expansion and collapse of VEGF diversity in major clades of the animal kingdom
Authors: Rauniyar Khushbu , Bokharaie Honey , Jeltsch Michael 
Published: September 2022

ABSTRACTThe vascular endothelial growth factor (VEGF) family comprises in vertebrates five or six members: VEGF(-A), PlGF, VEGF-B, VEGF-C, VEGF-D, and – in venomous reptiles – VEGF-F. They fulfill mainly functions for the blood and lymphatic vascular systems. Together with the platelet-derived growth factors (PDGF-A to -D), they form the PDGF/VEGF subgroup among cystine-knot growth factors. Despite an absent vascular system in most invertebrates, PDGF/VEGF-like molecules have been found in, e.g.,Drosophila melanogasterandCaenorhabditis elegans. The evolutionary relationship between PDGF and VEGF growth factors has only been addressed by older analyses, which were limited by the sparse sequencing data at the time. Here we perform a comprehensive analysis of the occurrence of PDGF/VEGF-like growth factors (PVFs) throughout all animal phyla and propose a likely phylogenetic tree. The three major vertebrate whole genome duplications play a role in the expansion of PDGF/VEGF diversity, but several limited duplications are necessary to account for the temporal pattern of emergence. The phylogenetically oldest PVFs likely featured a C-terminus with a BR3P signature, a hallmark of the modern-day lymphangiogenic growth factors VEGF-C and VEGF-D. Some of the youngerVEGFgenes appeared completely absent in some clades, e.g., functionalVEGFBgenes in the clade Archosauria, which includes crocodiles, birds, and other dinosaurs, andpgfin amphibians. The lack of precise counterparts for human genes poses limitations but also offers opportunities for research using organisms that diverge considerably from humans if the goal is to understand human physiology.Graphical abstractSources for the graphical abstract:326 MYA and older [1]272-240 MYA [2]235-65 MYA [3]
saks-nf: A json solution for Nextflow pipeline construction
Authors: Zhuo Xinming , Renzette Nicholas , Omerza Gregory 
Published: September 2022

AbstractTo address the increasing complexity of data in scientific research, researchers have developed many workflow manager tools. Nextflow is one of the most widely used tools, enabling scalability and reproducibility of scientific workflows across various computational platforms through the implementation of domain-specific language (DSL) with a dataflow paradigm. We developed saks-nf, a JavaScript Object Notation (JSON) solution for constructing Nextflow pipelines. Our solution flattens the learning curve for Nextflow. Users can build and maintain a pipeline without prior programming experience by editing a JSON specification on any text editor. The saks-nf solution can be used to construct a multi-step pipeline with parallel and scatter-gather capacity in a computing platform of choice, such as a local machine, a high-performance cluster, or cloud computing. This solution allows users to focus on analysis, thereby increasing productivity.
Visual processing and collective motion-related decision-making in desert locusts
Authors: Bleichman Itay , Yadav Pratibha , Ayali Amir 
Published: September 2022

AbstractCollectively moving groups of animals rely on the decision-making of locally interacting individuals in order to maintain swarm cohesion. However, the complex and noisy visual environment poses a major challenge to the extraction and processing of relevant information. We addressed this challenge by studying swarming-related decision-making in desert locust last-instar nymphs. Controlled visual stimuli, in the form of random dot kinematograms, were presented to tethered locust nymphs in a trackball setup, while monitoring movement trajectory and walking parameters. In a complementary set of experiments, the neurophysiological basis of the observed behavioral responses was explored. Our results suggest that locusts utilize filtering and discrimination upon encountering multiple stimuli simultaneously. Specifically, we show that locusts are sensitive to differences in speed at the individual conspecific level, and to movement coherence at the group level, and may use these to filter out non-relevant stimuli. The locusts also discriminate and assign different weights to different stimuli, with an observed interactive effect of stimulus size, relative abundance, and motion direction. Our findings provide insights into the cognitive abilities of locusts in the domain of decision-making and visual-based collective motion, and support locusts as a model for investigating sensory-motor integration and motion-related decision-making in the intricate swarm environment.
Effect and mechanism of black soybean peptides alleviating oxidative damage in the celiac disease cell model
Authors: Cui Chenxu , Wang Na , Gao Enguang , Sun Xuefeng , Yu Qiuying , Hu Man , Xu Qian , Cui Ningnig , Zheng Yuru , Wang Chunfeng , Wang Fangyu 
Published: September 2022

AbstractAlpha gliadin peptide induces damage and apoptosis of intestinal cells and aggravates pathology of celiac disease (CD) by inducing oxidative stress. Therefore, inhibition or alleviation of oxidative stress in CD may be an effective approach to the adjunctive treatment of CD. Black soybean peptides (BSPs) have been shown to inhibit oxidative stress and inflammation. The effect of BSPs on CD remains unknown. In this paper, the effect and mechanism of BSPs on the α-gliadin peptide (p31-43)-induced Caco-2 cytotoxicity were studied. We identified BSPs that alleviated the cytotoxicity of p31-43 in the CD cell model: Caco-2 cells were pre-treated with bioactive peptides for 3 hours before the addition of p31-43 for treatment for 24 hours, and then cells were collected for subsequent experiments. Our results show that p31-43 can significantly increase the ROS and MDA levels of Caco-2 cells, disrupt the glutathione redox cycle, reduce the activity of the antioxidant enzyme, and inhibit the activation of antioxidant signaling pathways. BSPs pretreatment can inhibit the increase of Keap1 protein induced by p31-43, activate antioxidant genes through Nrf2 protein, improve the activity of the antioxidant enzyme, alleviates glutathione redox cycle imbalance, promote the expression of GCLC or GCLM, and reduce oxidative damage.Graphical AbstractPattern of BSPs against oxidative damage in CD cell mode.
Water wisteria genome reveals environmental adaptation and heterophylly regulation in amphibious plants
Authors: Li Gaojie , Zhao Xuyao , Yang Jingjing , Hu Shiqi , Ponnu Jathish , Kimura Seisuke , Hwang Inhwan , Torii Keiko U , Hou Hongwei 
Published: September 2022

AbstractHeterophylly is a phenomenon in which an individual plant dramatically changes its leaf shape in response to the surrounding environment.Hygrophila difformis(Acanthaceae), also known as water wisteria, has recently emerged as a model plant to study heterophylly because of its striking leaf shape variation in response to various ecological factors. Under submerged conditions,H. difformisdevelops complex leaves and in terrestrial conditions it develops simple leaves. Here, we sequenced and assembled the chromosome-level genome of triploidH. difformis(scaffold N50: 60.43 Mb, genome size: 871.92 Mb), which reveals 36,099 predicted protein-coding genes distributed over 15 pseudochromosomes.H. difformisdiverged from its relatives during the Oligocene climate-change period and expanded the gene families related to its amphibious lifestyle. Genes involved in environmental stimuli, leaf development, and other pathways are differentially expressed in submerged and terrestrial conditions, possibly modulating morphological and physiological acclimation to changing environments. We confirmed that auxin plays a role in the heterophylly ofH. difformis. Finally, we discovered candidate genes that respond to different environmental conditions and elucidated the role ofLATE MERISTEM IDENTITY 1(LMI1) in heterophylly. Our study establishesH. difformisas a model for studying the interconnections between ecological adaptation and plant morphological features.
Seeing speech: The cerebral substrate of tickertape synesthesia
Authors: Hauw Fabien , El Soudany Mohamed , Rosso Charlotte , Daunizeau Jean , Cohen Laurent 
Published: September 2022

AbstractReading acquisition is enabled by deep changes in the brain’s visual system and language areas, and in the links subtending their collaboration. Disruption of those plastic processes commonly results in developmental dyslexia. However, atypical development of reading mechanisms may occasionally result in ticker-tape synesthesia (TTS), a condition described by Francis Galton in 1883 wherein individuals “see mentally in print every word that is uttered (…) as from a long imaginary strip of paper”. While reading is the bottom-up translation of letters into speech, TTS may be viewed as its opposite, the top-down translation of speech into internally visualized letters. In a series of functional MRI experiments, we studied MK, a man with TTS. We showed that a set of left-hemispheric areas were more active in MK than in controls during the perception of normal than reversed speech, including frontoparietal areas involved in speech processing, and the Visual Word Form Area, an occipitotemporal region subtending orthography. Those areas were identical to those involved in reading, supporting the construal of TTS as upended reading. Using dynamic causal modeling, we further showed that, parallel to reading, TTS induced by spoken words and pseudowords relied on top-down flow of information along distinct lexical and phonological routes, involving the middle temporal and supramarginal gyri, respectively. Future studies of TTS should shed new light on the neurodevelopmental mechanisms of reading acquisition, their variability and their disorders.Significance statementSome individuals, whenever they are hearing speech, see vividly in their mind’s eye the corresponding words in written form, as mental subtitles. This unusual condition, termed ticker-tape synesthesia (TTS), far from being purely anecdotal, actually touches on the core of the brain mechanisms of normal and impaired reading acquisition. Through 3 fMRI experiments, plus brain connectivity analyses, we propose an in-depth study of a single individual with such ticker-tape synesthesia. We propose that TTS, a situation in some sense symmetrical to developmental dyslexia, reflects an inverted flow of information through the reading system, such that speech is automatically translated into internally visualized letters. Future studies of TTS should shed new light on the neurodevelopmental mechanisms of reading acquisition.
Non-targeted isomer-sensitive N-glycome analysis reveals new layers of organ-specific diversity in mice
Authors: Helm Johannes , Mereiter Stefan , Oliveira Tiago , Gattinger Anna , Markovitz David M. , Penninger Josef M. , Altmann Friedrich , Stadlmann Johannes 
Published: September 2022

SummaryN-glycosylation is one of the most common protein modifications in eukaryotes, with immense importance at the molecular, cellular, and organismal level. Accurate and reliable N-glycan analysis is essential to obtain a systems-wide understanding of fundamental biological processes. Due to the structural complexity of glycans, their analysis is still highly challenging. Here we make publicly available a consistent N-glycome dataset of 20 different mouse tissues and demonstrate a multimodal data analysis workflow that allows for unprecedented depth and coverage of N-glycome features. This highly scalable, LC-MS/MS data-driven method integrates the automated identification of N-glycan spectra, the application of non-targeted N-glycome profiling strategies and the isomer-sensitive analysis of glycan structures. Our delineation of critical sub-structural determinants and glycan isomers across the mouse N-glycome uncovered tissue-specific glycosylation patterns, the expression of non-canonical N-glycan structures and highlights multiple layers of N-glycome complexity that derive from organ-specific regulations of glycobiological pathways.
Genome-wide fixation under viability selection
Authors: Eldon Bjarki 
Published: September 2022

AbstractWe investigate through simulations the effect of random sweepstakes, recurrent bottlenecks, dominance, and epistasis on selection a diploid population when the phenotype is determined by the genotype at a number of unlinked sites. We assume there are two types at each site, the wild type and a type conferring selective advantage. The focus is on identifying main trends in how the stated elements impact selection when selection acts on at least two unlinked site. We give examples of fixation trajectories under an array of scenarios, and record corresponding numerical estimates of the probability of fixation of the fit type at all the sites in question each time, and the time to fixation conditional on fixation. The results suggest that joint fixation of the fit type at the sites can occur in a number of scenarios, despite starting with the fit type in a single copy at each site. Random sweepstakes generally reduce both the probability and the time to fixation (conditional on fixation). Recurrent strong bottlenecks generally reduce the probability of fixation, but the effect of bottlenecks on the time to fixation (conditional on fixation), depends on the dominance mechanism in question. We identify an example of epistasis where fixation can occur, when in the absence of epistasis fixation does not occur at all or with much lower probability. Our results, coupled with an extensive analysis of genomic data of Atlantic cod(4), is further evidence for pervasive strong positive selection as being a key driving force in the evolution at least of highly fecund populations.
Unlocking the hidden genetic diversity of varicosaviruses, the neglected plant rhabdoviruses
Authors: Bejerman Nicolás , Dietzgen Ralf G. , Debat Humberto 
Published: September 2022

AbstractThe genus Varicosavirus is one of six genera of plant-infecting rhabdoviruses. Varicosaviruses have nonenveloped flexuous rod-shaped virions and a negative-sense, single-stranded RNA genome. A distinguishing feature of varicosaviruses, that is shared with dichorhaviruses, is a bi-segmented genome. Before 2017, a sole varicosavirus was known and characterized, then two more varicosaviruses were identified through high-throughput sequencing in 2017 and 2018. More recently, the number of known varicosaviruses has substantially increased in concert with the extensive use of high-throughput sequencing platforms and data mining approaches. The novel varicosaviruses revealed not only sequence diversity but also plasticity in terms of genome architecture, including a virus with a tentatively unsegmented genome. Here, we report the discovery of 45 novel varicosavirus genomes, which were identified in publicly available metatranscriptomic data. Identification, assembly, and curation of raw Sequence Read Archive reads resulted in 39 viral genome sequences with full-length coding regions and 6 with nearly complete coding regions. Highlights of the obtained sequences include eight varicosaviruses with unsegmented genomes, linked to a phylogenetic clade associated with gymnosperms. These findings resulted in the most complete phylogeny of varicosaviruses to date and shed new light on the phylogenetic relationships and evolutionary landscape of this group of plant rhabdoviruses. Thus, the extensive use of sequence data mining for virus discovery has allowed unlocking of the hidden genetic diversity of varicosaviruses, the largely neglected plant rhabdoviruses.