bluuebunny/crossref_metadata_2025 huggingface dataset:
Guild-level microbiome signature associated with COVID-19 severity and prognosis
Authors: Guo Mingquan , Wu Guojun , Tan Yun , Li Yan , Jin Xin , Qi Weiqiang , Guo XiaoKui , Zhang Chenhong , Zhu Zhaoqin , Zhao Liping
Published: September 2022

COVID-19 severity has been associated with alterations of the gut microbiota. However, the relationship between gut microbiome alterations and COVID-19 prognosis remains elusive. Here, we performed a genome-resolved metagenomic analysis on fecal samples collected from 300 in-hospital COVID-19 patients at time of admission. Among the 2,568 high quality metagenome-assembled genomes (HQMAGs), Redundancy Analysis identified 33 HQMAGs which showed differential distribution among mild, moderate, and severe/critical severity groups. Random Forest model based on these 33 HQMAGs classified patients from different severity groups (average AUC = 0.79). Co-abundance network analysis found that the 33 HQMAGs were organized as two competing guilds. Guild 1 harbored more genes for short-chain fatty acid biosynthesis, and fewer genes for virulence and antibiotic resistance, compared with Guild 2. Random Forest regression showed that these 33 HQMAGs at admission had the capacity to predict 8 clinical parameters, which are predictors for COVID-19 prognosis, at Day 7 in hospital. Moreover, the dominance of Guild 1 over Guild 2 at admission predicted the death/discharge outcome of the critical patients (AUC = 0.92). Random Forest models based on these 33 HQMAGs classified patients with different COVID-19 symptom severity, and differentiated COVID-19 patients from healthy subjects, non-COVID-19, and pneumonia controls in three independent datasets. Thus, this genome-based guild-level signature may facilitate early identification of hospitalized COVID-19 patients with high risk of more severe outcomes at time of admission.
A spatiotemporal map of the aging mouse brain reveals white matter tracts as vulnerable foci
Authors: Hahn Oliver , Foltz Aulden G , Atkins Micaiah , Kedir Blen , Moran-Losada Patricia , Guldner Ian H , Munson Christy , Kern Fabian , Pálovics Róbert , Lu Nannan , Zhang Hui , Kaur Achint , Hull Jacob , Huguenard John R , Grönke Sebastian , Lehallier Benoit , Partridge Linda , Keller Andreas , Wyss-Coray Tony
Published: September 2022

Aging is the key risk factor for cognitive decline, yet the molecular changes underlying brain aging remain poorly understood. Here, we conducted spatiotemporal RNA-seq of the mouse brain, profiling 1,076 samples from 15 regions across 7 ages and 2 rejuvenation interventions. Our analysis identified a brain-wide gene signature of aging in glial cells, which exhibited spatially defined changes in magnitude. By integrating spatial and single-nucleus transcriptomics, we found that glia aging was particularly accelerated in white matter compared to cortical regions, while specialized neuronal populations showed region-specific expression changes. Rejuvenation interventions, including young plasma injection and dietary restriction, exhibited distinct effects on gene expression in specific brain regions. Furthermore, we discovered differential gene expression patterns associated with three human neurodegenerative diseases, highlighting the importance of regional aging as a potential modulator of disease. Our findings identify molecular foci of brain aging, providing a foundation to target age-related cognitive decline.
Multi-modal Efficacy of a Chimeric Vesiculovirus Expressing the Morreton Glycoprotein in Sarcoma
Authors: Dumbauld Chelsae , Barro Oumar , Elliott Natalie M. , Zhou Yumei , Gabere Musa , Raupach Elizabeth , Baker Alexander T. , Barrett Michael T. , Buetow Kenneth H. , Jacobs Bertram , Seetharam Mahesh , Borad Mitesh J. , Nagalo Bolni Marius
Published: September 2022

Vesiculoviruses are attractive oncolytic virus (OV) platforms due to their rapid replication, genome with appreciable transgene capacity, broad tropism, limited pre-existing immunity, and type I interferon response gradient between malignant and normal cells. We developed a synthetic chimeric virus (VMG) expressing the glycoprotein (G) from Morreton virus (MorV) with remaining genes from vesicular stomatitis virus (VSV). VMG exhibited in vitro efficacy in cell proliferation and cell death assays across a broad range of sarcoma subtypes and across multiple species. Notably, all cell lines tested showed ability of VMG to yield productive infections with rapid replication kinetics. Pilot safety evaluations of VMG in immunocompetent, non-tumor bearing mice showed absence of toxicity with intranasal doses as high as 1e10 TCID50. VMG resulted in tumor reduction in vivo in an immunodeficient subcutaneous Ewing sarcoma model at doses as low as 2e5 TCID50. In the immune competent murine syngeneic fibrosarcoma model, while no tumor inhibition was achieved with VMG, there was a robust induction of CD8+ T cells suggestive of potential for combination approaches with immunomodulatory agents such as immune checkpoint inhibitors. The studies described herein establish the potential for VMG as a novel oncolytic virotherapy platform with multi-modal anti-tumor effects in sarcoma.
HCR Lateral Flow Assays for Amplified Instrument-Free At-Home SARS-CoV-2 Testing
Authors: Schulte Samuel J. , Huang Jining , Pierce Niles A.
Published: September 2022

The lateral flow assay format enables rapid, instrument-free, at-home testing for SARS-CoV-2. Due to the absence of signal amplification, this simplicity comes at a cost in sensitivity. Here, we enhance sensitivity by developing an amplified lateral flow assay that incorporates isothermal, enzyme-free signal amplification based on the mechanism of hybridization chain reaction (HCR). The simplicity of the user experience is maintained using a disposable 3-channel lateral flow device to automatically deliver reagents to the test region in three successive stages without user interaction. To perform a test, the user loads the sample, closes the device, and reads the result by eye after 60 minutes. Detecting gamma-irradiated SARS-CoV-2 virions in a mixture of saliva and extraction buffer, the current amplified HCR lateral flow assay achieves a limit of detection of 200 copies/μL using available antibodies to target the SARS-CoV-2 nucleocapsid protein. By comparison, five commercial unamplified lateral flow assays that use proprietary antibodies exhibit limits of detection of 500 copies/μL, 1000 copies/μL, 2000 copies/μL, 2000 copies/μL, and 20,000 copies/μL. By swapping out antibody probes to target different pathogens, amplified HCR lateral flow assays offer a platform for simple, rapid, and sensitive at-home testing for infectious disease. As an alternative to viral protein detection, we further introduce an HCR lateral flow assay for viral RNA detection.

HCR lateral flow assay

Amplified

Instrument-free

At-home

60 min

Naked eye

SARS-CoV-2

200 copies/μL
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

Purpose

Lamina 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.

Methods

The 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.

Results

Both 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.

Conclusions

Increasing 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 Relevance

Additional 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.

Precis

The 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

Antibiotic 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.

Importance

Rising 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

Class 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.

Significance

Although 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

The 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 abstract

Sources 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

To 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.
Loss of Rab8a in B cells leads to increased antibody responses and class-switch recombination
Authors: Hernández-Pérez Sara , Sarapulov Alexey V. , Balci M. Özge , Coffey Eleanor , Harada Akihiro , Mattila Pieta K.
Published: September 2022

Rab8a is a small GTPase with a wide range of reported functions in different cell types, including vesicle recycling, vesicle traffic to cilia, cell ruffling, migration, neurite outgrowth, Toll-like receptor signalling and T cell receptor docking at the immune synapse. However, the role of Rab8a in B lymphocytes has not been described to date. Here, using a conditional B cell-specific Rab8a knockout mouse model, we investigate the role of Rab8a bothin vivoandin vitro. Rab8a KO mice present enhanced antibody responses to both T-dependent and T-independent immunisations. Rab8a KO cells showed normal BCR trafficking and antigen processing and presentation but however, increased class-switch recombination. While the early BCR signalling responses, such as proximal kinase activation and calcium-flux, were normal, the signalling via AKT and ERK1/2 was decreased. We propose that the lack of Rab8a alters cellular signalling leading to enhanced antibody responses and increased class-switch recombination potentially via downmodulation of the PI3K/AKT/mTOR pathway.
Visual processing and collective motion-related decision-making in desert locusts
Authors: Bleichman Itay , Yadav Pratibha , Ayali Amir
Published: September 2022

Collectively 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

Alpha 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 Abstract

Pattern 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

Heterophylly 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

Reading 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 statement

Some 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

N-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

We 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

The 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.
Long-read powered viral metagenomics in the Oligotrophic Sargasso Sea
Authors: Warwick-Dugdale Joanna , Tian Funing , Michelsen Michelle , Cronin Dylan R , Moore Karen , Farbos Audrey , Chittick Lauren , Bell Ashley , Buchholz Holger H , Parsons Rachel J , Zayed Ahmed A , Allen Michael J , Sullivan Matthew B , Temperton Ben
Published: September 2022

In the summer months, the waters of the Sargasso Sea are nutrient-limited and strongly stratified, serving as a model system for the predicted warmer and nutrient-limited oceans of the Anthropocene. The dominant microorganisms of surface waters are key drivers of the global carbon cycle. However, the viruses of the Sargasso Sea that shape these host communities and influence host biogeochemical function are not well understood. Here, we apply a hybrid sequencing approach that combines short- and long reads to survey Sargasso Sea phage communities via metagenomics at the viral maximum (80m) and mesopelagic (200m) depths. Taxonomically, we identified 2,301 Sargasso Sea phage populations (~species-level taxonomy) across 186 genera. Over half of the phage populations lacked representation in other global ocean viral metagenomes, whilst 177 phage genera lacked representation in phage isolate databases. Viral fraction and cell-associated viral communities captured in short-read data were distinct and decoupled at both depths, possibly indicating low active lytic viral replication in the Sargasso Sea, with viral turnover occurring across periods longer than the sampling period of three days. Inclusion of long read data was critical for (1) the identification of 79 ecologically important and common viral genomes; (2) capturing the extent of viral genome microdiversity; and (3) enabling the recovery of hypervariable regions in viral genomes predicted to encode proteins involved in host recognition, DNA synthesis and DNA packaging. Host prediction was only possible for ~4% of viral populations. Genomes of phages known to infect Prochlorococcus and Pelagibacter were poorly represented in our data, supporting recent evidence of low infection levels in the dominant bacterial taxa of oligotrophic regions.

Subjects

Bioinformatics, Genomics, Marine Biology, Microbiology, Virology

Sequence data accession numbers

PRJNA767318
The assessment of cortical hemodynamic responses induced by tubuloglomerular feedback using in vivo imaging
Authors: Lee Blaire , Postnov Dmitry D. , Sørensen Charlotte M. , Sosnovtseva Olga
Published: September 2022

The tubuloglomerular feedback (TGF) mechanism is crucial in modulating renal hemodynamics and glomerular filtration rate in individual nephrons. Our study aimed to evaluate the TGF-induced vascular responses by comparing the effects of two transport inhibitors with different sites and mechanisms of action. We assessed cortical hemodynamics with high-resolution laser speckle contrast imaging, which enabled the evaluation of blood flow individual micro-vessels and analysis of their dynamical patterns in the time-frequency domain. We demonstrated that a systemic administration of a loop diuretic abolishes TGF-mediated hemodynamic responses. Furthermore, we showed that the local microcirculatory blood flow decreased, and the TGF reset in response to reduced proximal reabsorption elicited by systemic administration of a sodium-glucose co-transporter 2 inhibitor, phlorizin.
PIKfyve is required for phagosomal Rab7 acquisition and the delivery and fusion of early macropinosomes to phagosomes
Authors: Vines James H. , Buckley Catherine M. , King Jason S.
Published: September 2022

Phagosome maturation is tightly regulated to ensure efficient delivery of the complex arsenal of antimicrobial activities that kill and digest captured microbes. Like other endocytic pathways, phagosome maturation is regulated by a combination of Rab GTPases and phosphoinositide signalling lipids (PIPs) which define membrane identity and recruit specific effectors. PIKfyve is a PI-5 kinase, which converts PI(3)P to PI(3,5)P2on endosomes. Disruption of PIKfyve results in severe defects in phagosomal maturation but the underlying mechanism remains unclear. Here, we use the model professional phagocyte,Dictyostelium discoideumto dissect the role of PIKfyve in the crucial first steps of phagosome maturation. We find that, although early Rab5 dynamics are unaffected, loss of PIKfyve prevents phagosomes from acquiring Rab7 by fusion with a pool of Rab7 and V-ATPase positive endosomes. By following PIP dynamics using our recently characterised PI(3,5)P2-probe SnxA, we delineate multiple subpopulations of Rab7-positive endosomes that fuse sequentially with phagosomes. We identify one of these as PI(3,5)P2-positive macropinosomes, which dock and fuse with phagosomes in a PIKfyve-dependent manner. We therefore show thatDictyosteliumphagosomes primarily accumulate Rab7 by vesicular fusion rather than from a cytosolic pool, and that this requires PIKfyve. In particular PI(3,5)P2defines a specific subset of fusogenic macropinosomes, which we propose enables content mixing and the efficient bulk delivery of lysosomal components to phagosomes.
Single and Multi-trait Genomic Prediction for agronomic traits inEuterpe edulis
Authors: Canal Guilherme Bravim , Barreto Cynthia Aparecida Valiati , de Almeida Francine Alves Nogueira , Zaidan Iasmine Ramos , do Couto Diego Pereira , Azevedo Camila Ferreira , Nascimento Moysés , Ferreira Marcia Flores da Silva , Ferreira Adésio
Published: September 2022

Popularly known as juçaizeiro,Euterpe edulishas been gaining prominence in the fruit growing sector and has demanded the development of superior genetic materials. As it is a native species and still little studied, the application of more sophisticated techniques can result in higher gains with less time. Until now, there are no studies that apply genomic prediction for this crop, especially in multi-trait analysis. In this sense, this study aimed to apply new methods and breeding techniques for the juçaizeiro, to optimize this breeding program through the application of genomic selection. This data consisted of 275 juçaizeiro genotypes from a population of Rio Novo do Sul-ES, Brazil. The genomic prediction was performed using the multi-trait (G-BLUP MT) and single-trait (G-BLUP ST) models and the selection of superior matrices was based on the selection index of Mulamba and Mock. Similar results for predictive ability were observed for both models. However, the G-BLUP ST model provided greater selection gains when compared to the G-BLUP MT. For this reason, the genomic estimated breeding values (GEBVs) from the G-BLUP ST were used to select the six superior genotypes (UFES.A.RN.390, UFES.A.RN.386, UFES.A.RN.080, UFES.A.RN.383, UFES.S.RN.098, and UFES.S.RN.093), to provide superior genetic materials for the development of seedlings and implantation of productive orchards, which will meet the demands of the productive, industrial and consumer market.

Key message

In the first genomic selection study forEuterpe edulis, substantial gains for multiple traits of fruit production was reported. This is a key factor for the sustainable use of the species in the Atlantic Forest.
Drought adaptability of different subspecies of tetraploid wheat (Triticum turgidum) under contrasting moisture conditions: association with solvent retention capacity and quality-related traits
Authors: Saeidnia F. , Shoormij F. , Mirlohi A. , Soleimani Kartalaei E. , Mohammadi M. , Sabzalian M. R.
Published: September 2022

Few prior efforts have been made to investigate the genetic potential of different subspecies of Triticum turgidum for drought tolerance and their quality-related traits compared with common wheat (Triticum aestivum) and to identify the association among agronomic, micronutrients, and quality-related traits, especially under climate change conditions. In this research, grain quality, technological properties of flour, and some agronomic traits were studied in 33 wheat genotypes from six different subspecies of Triticum turgidum along with three cultivars of Triticum aestivum in the field, applying a well-watering (WW) and a water stress (WS) environment during two growing seasons. A high degree of variation was observed among genotypes for all evaluated traits, demonstrating that selection for these traits would be successful. Consequences of water stress were manifested as declined DM, TGW, GY, and LASRC; and significantly increased GPC, ZEL, GH, WAF, WSRC, SuSRC, and SCSRC compared to the well-watering condition. The reductions in the unextractable polymeric protein fraction and glutenin-to-gliadin ratio indicated a poorer grain yield quality, despite higher protein content. This study showed that the early-maturing genotypes had higher water absorption and pentosan, and therefore are more suitable for bread baking. In contrast, late-maturing genotypes are ideal for cookie and cracker production. Two subspecies of T. turgidum ssp. durum and T. turgidum ssp. dicoccum with high micronutrient densities and quality-related traits, and T. turgidum ssp. oriental due to having high values of grain protein content can be used to improve the quality of T. aestivum through cross-breeding programs. Based on the association of different traits with SRC values and other quality-related traits and PCA results, contrasting genotypes can be used to develop mapping populations for genome studies of grain quality and functional properties of flour in future studies.
The homeobox transcription factor DUXBL controls exit from totipotency
Authors: Vega-Sendino Maria , Olbrich Teresa , Stein Paula , Tillo Desiree , Carey Grace I. , Savy Virginia , Saykali Bechara , Domingo Catherine N. , Maity Tapan K. , Jenkins Lisa M. , Williams Carmen J. , Ruiz Sergio
Published: September 2022

Upon exit from the totipotent 2-cell (2C) embryo stage, the 2C-associated transcriptional program needs to be efficiently silenced. However, the molecular mechanisms involved in this process remain mostly unknown. Here, we demonstrate that the 2C-specific transcription factor DUX directly induces the expression of DUXBL to promote this silencing. Indeed, DUX expression in Duxbl-knockout ESC causes increased induction of the 2C-transcriptional program, whereas DUXBL overexpression impairs 2C-associated transcription. CUT&RUN analyses show that DUXBL gains accessibility to DUX-bound regions in DUX-induced ESC while it is unable to bind those regions in uninduced cells. Mechanistically, we determined that DUXBL interacts with TRIM24 and TRIM33, two members of the tripartite motif superfamily involved in gene silencing and co-localizes with them in nuclear foci upon DUX expression. Furthermore, DUXBL downregulation in mouse zygotes leads to a penetrant 2C-stage arrest. Our data reveals an unexpected role for DUXBL in controlling the exit from totipotency.
Expression of thioredoxin-1 in the ASJ neuron corresponds with and enhances intrinsic regenerative capacity under lesion conditioning inC. elegans
Authors: Grooms Noa W.F. , Fitzgerald Michael Q. , Zuckerman Binyamin , Ureña Samuel E. , Weinberger Leor S. , Chung Samuel H.
Published: September 2022

A conditioning lesion of the peripheral sensory axon triggers robust central axon regeneration in mammals. We trigger conditioned regeneration in theC. elegansASJ neuron by laser surgery or genetic disruption of sensory pathways. Conditioning upregulatestrx-1expression, as indicated bytrx-1promoter-driven green fluorescent protein and fluorescence in situ hybridization, suggestingtrx-1levels and associated fluorescence indicate regenerative capacity. Redox activity oftrx-1functionally enhances conditioned regeneration, but both redox-dependent and –independent activity inhibit non-conditioned regeneration. Six strains isolated in a forward genetic screen for reduced fluorescence, which suggests diminished regenerative potential, also show reduced axon outgrowth. We demonstrate an association betweentrx-1expression and the conditioned state that we leverage to rapidly assess regenerative capacity.
A neuron that regulates locomotion makes a potential sensory cilium lying over the C. elegans egg-laying apparatus
Authors: Christie Nakeirah T.M. , Koelle Michael R.
Published: September 2022

The neural circuit for C. elegans egg laying has been studied intensively for decades, yet it is not clear that its known components can account for how egg-laying and locomotion behaviors are coordinated. We found that the two PVP neurons, which release neuropeptides that promote roaming locomotion, make previously-undescribed branches that terminate in large wing-shaped endings directly over the egg-laying apparatus. The PVP branches occur in hermaphrodites but not males and develop during the L4 larval stage when the egg-laying system also develops. The PVP wing is located at the junction between the uterus and the vulva, adjacent to neurons that control egg laying, and surrounded by cells that we found label with a glial marker. The morphology of the PVP wing and its envelopment within possible glial cells are consistent with the hypothesis that the PVP wing is a sensory cilium. Although PVP is reported to express sensory receptor homologs, we have been unable to detect PVP expression of more specific markers of neural cilia, and we have also not detected strong PVP defects in the daf-19 mutant, which does show defects in known neural cilia. The PVPs are extraordinarily sensitive to expression of transgenes, which cause developmental and possibly functional defects in these neurons. This has prevented us from recording or manipulating PVP activity to determine its functional roles. Thus, the intriguing hypothesis that PVP is a sensory neuron that might coordinate egg laying and locomotion will remain speculative until better methods to manipulate PVP can be developed.
Analysis of polygenic selection in purebred and crossbred pig genomes using Generation Proxy Selection Mapping
Authors: Grohmann Caleb J. , Shull Caleb M. , Crum Tamar E. , Schwab Clint , Safranski Timothy J. , Decker Jared E.
Published: September 2022

Background

Artificial selection on quantitative traits using breeding values and selection indices in commercial livestock breeding populations causes changes in allele frequency over time, termed polygenic selection, at causal loci and the surrounding genomic regions. Researchers and managers of pig breeding programs are motivated to understand the genetic basis of phenotypic diversity across genetic lines, breeds, and populations using selection mapping analyses. Here, we applied Generation Proxy Selection Mapping (GPSM), a genome-wide association analysis of SNP genotype (38,294 to 46,458 SNPs) of birth date, in four pig populations (15,457, 15,772, 16,595 and 8,447 pigs per population) to identify loci responding to artificial selection over a span of five to ten years. Gene-drop simulation analyses were conducted to validate GPSM results. Selection signatures within and across each population of pigs were compared in the context of commercial pork production.

Results

Forty-nine to 854 loci were identified by GPSM as under selection (Q-values less than 0.10) across 15 subsets of pigs based on population combinations. The number of significant associations increased as populations of pigs were pooled. In addition, several significant associations were identified in more than one population. These results indicate concurrent selection objectives, similar genetic architectures, and shared causal variants responding to selection across populations. Negligible error rates (less than or equal to 0.02%) of false-positive associations were identified when testing GPSM on gene-drop simulated genotypes, suggesting that GPSM distinguishes selection from random genetic drift in actual pig populations.

Conclusions

This work confirms the efficacy and accuracy of the GPSM method in detecting selected loci in commercial pig populations. Our results suggest shared selection objectives and genetic architectures across swine populations. Identified polygenic selection highlights loci important to swine production.