bluuebunny/crossref_metadata_2025_split huggingface dataset:
A survey of lineage-specific genes in Triticeae reveals de novo gene evolution from genomic raw material
Authors: Poretti Manuel , Praz Coraline R. , Sotiropoulos Alexandros G. , Wicker Thomas 
Published: May 2022

AbstractPlant genomes typically contain ∼35,000 genes, almost all belonging to highly-conserved gene families. Only a small fraction are lineage-specific, which are found in only one or few closely related species. Little is known about how genes arise de novo in plant genomes and how often this occurs, however they are believed to be important for plants diversification and adaptation. We developed a pipeline to identify lineage-specific genes in Triticeae, using newly available genome assemblies of wheat, barley and rye. Applying a set of stringent criteria, we identified 5,942 candidate Triticeae-specific genes (TSGs), of which 2,337 were validated as protein-coding genes in wheat. Differential gene expression analyses revealed that stress-induced wheat TSGs are strongly enriched in secreted proteins. Some were previously described to be involved in Triticeae non-host resistance and cold adaptation. Additionally, we show that 1,079 TSGs have sequence homology to transposable elements (TEs), ∼68% of them deriving from regulatory non-coding regions of Gypsy retrotransposons. Most importantly, we demonstrate that these TSGs are enriched in transmembrane domains and are among the most highly expressed wheat genes overall. To summarize, we conclude that de novo gene formation is relatively rare and that Triticeae probably possess ∼779 lineage-specific genes per haploid genome. TSGs which respond to pathogen and environmental stresses, may be interesting candidates for future targeted resistance breeding in Triticeae. Finally, we propose that non-coding regions of TEs might provide important genetic raw material for the functional innovation of TM domains and the evolution of novel secreted proteins.
Development and Evaluation of a Colloidal Gold Immunofiltration Assay for Penside Diagnosis of Visceral Schistosomosis in Cattle
Authors: Mamane Shivani , Jeyathilakan N. , Latha Bhaskaran. Ravi. , Senthilkumar T. M. A. 
Published: May 2022

AbstractBackgroundVisceral schistosomosis caused by Schistosoma spindale is an economically important chronic wasting snail-borne trematode infection which often goes undiagnosed in field condition due to lack of efficient diagnostic assays. ELISA and Colloidal gold immunofiltration assay were used to evaluate the state of active visceral schistosomosis in cattle through detection of antibodies against S. spindale ES antigen.Methodology/Principle FindingsThe present study included development and evaluation of enzyme linked immunosorbent assay (ELISA) and colloidal gold immunofiltration assay (CGIFA) with conventionally prepared S. spindale excretory-secretory (ES) antigen using postmortem mesenteric examination as a reference standard. Statistical analysis was performed using Cochran Q test, Chi-square test and kappa statistics which showed no significant difference between the developed tests and strong agreement with the postmortem examination which was considered as gold standard test. CGIFA showed sensitivity, specificity and accuracy of 92.98 %, 96.74 % and 95.55 % respectively whereas that of ELISA was 94.73 %, 95.12 % and 95% respectively.Conclusion/SignificanceCGIFA was found to be simpler, rapid, effective, less expensive and required least expertise for interpretation of results. It can be used as portable diagnostic device for rapid diagnosis of S. spindale infection at field condition making it an ideal pen side diagnostic kit.
The H3K27me3 epigenetic mark is crucial for callus cell identity and for the acquisition of new fate during root and shoot regeneration
Authors: Mandel Tali , Landau Udi , Kaplan Tommy , Williams Leor Eshed 
Published: May 2022

AbstractWe combined molecular, genomic and genetic approaches to study the molecular mechanisms underlying cell totipotency and competency to regenerate in Arabidopsis.By performing comparative analysis of mRNA-seq and chromatin landscapes between leaf differentiated cells and callus totipotent cells and between WT callus and calli derived from theemf2mutant, exhibiting impaired regenerative capacity we revealed the following:1. That callus cells express numerous genes of many developmental pathways such as root, leaf, embryo, shoot, meristem and seed. This suggests a mechanism to allow rapid response to a signal by maintaining genes of all potential developmental pathways active, without the needs to release transcriptional silencing and to go through the intricate multistep process of transcription.2. That key transcription factors that are sufficient to derive differentiation or organogenesis are silenced and marked by the H3K27me3.3. That callus derived from theemf2mutant which is impaired in setting the H3K27methylation, lost the capacity to regenerate and that 78 transcription factors from which 18 regulate flower development, where up-regulated compared with WT callus.Altogether our results suggest that competency to regenerate is achieved by keeping the chromatin of developmental genes active, and that upon a signal for cell fate switch, a mechanism to repress those genes is required to allow the one desired developmental pathway to dominate. When this mechanism is impaired the capacity to regenerate is decline.
Locus cœruleus noradrenergic neurons phase-lock to prefrontal and hippocampal infra-slow rhythms that synchronize to behavioral events
Authors: Xiang Liyang , Harel Antoine , Todorova Ralitsa , Gao HongYing , Sara Susan J. , Wiener Sidney I. 
Published: May 2022

AbstractThe locus cœruleus (LC) is the primary source of noradrenergic projections to the forebrain, and, in prefrontal cortex, is implicated in decision-making and executive function. LC neurons phase-lock to cortical infra-slow wave oscillations during sleep. Such infra-slow rhythms are rarely reported in awake states, despite their interest, since they correspond to the time scale of behavior. Thus, we investigated LC neuronal synchrony with infra-slow rhythms in awake rats performing an attentional set-shifting task. Local field potential (LFP) oscillation cycles in prefrontal cortex and hippocampus on the order of 0.4 Hz phase-locked to task events at crucial maze locations. Indeed, successive cycles of the infra-slow rhythms showed different wavelengths, as if they are periodic oscillations that can reset phase relative to salient events.Simultaneously recorded infra-slow rhythms in prefrontal cortex and hippocampus could show different cycle durations as well suggesting independent control. Most LC neurons (including optogenetically identified noradrenergic neurons) recorded here were phase-locked to these infra-slow rhythms, as were hippocampal and prefrontal units recorded on the LFP probes. The infra-slow oscillations also phase-modulated gamma amplitude, linking these rhythms at the time scale of behavior to those coordinating neuronal synchrony. This would provide a potential mechanism where noradrenaline, released by LC neurons in concert with the infra-slow rhythm, would facilitate synchronization or reset of these brain networks, underlying behavioral adaptation.
Hypoxic memory of tumor intrinsic type I interferon suppression promotes breast cancer metastasis
Authors: Iriondo Oihana , Mecenas Desirea , Li Yilin , Chin Christopher R. , Thomas Amal , Amzaleg Yonatan , Moriarty Aidan , Ortiz Veronica , MacKay Matthew , Dickerson Amber , Lee Grace , Harotoonian Sevana , Benayoun Bérénice A. , Smith Andrew , Mason Christopher , Torres Evanthia T. Roussos , Klotz Remi , Yu Min 
Published: May 2022

AbstractHypoxia is a common feature of many solid tumors due to aberrant proliferation and angiogenesis and has been associated with tumor progression and metastasis. Most of the well-known hypoxia effects are mediated through hypoxia-inducible factors (HIFs), but the long-lasting effect of hypoxia beyond the immediate HIF regulation remains less understood. Here we show that hypoxia exerts a prolonged effect to promote metastasis. Using breast cancer patient-derived circulating tumor cell (CTC) lines and common breast cancer cell lines, we found that hypoxia downregulates tumor intrinsic type I interferon (IFN) signaling and its downstream antigen presentation (AP) machinery in luminal breast cancer cells, via both HIF-dependent and HIF-independent mechanisms. Hypoxia induced IFN/AP suppression can last longer than the hypoxic exposure, presenting a “hypoxic memory” phenotype. Hypoxic memory of IFN/AP downregulation is established by specific hypoxic priming, and cells with hypoxic memory have an enhanced ability for tumorigenesis and metastasis. The histone deacetylase inhibitor (HDACi) Entinostat can erase the hypoxic memory and improve the immune clearance of tumor cells when combined with checkpoint immunotherapies in a syngeneic breast cancer mouse model. These results point to a novel mechanism for hypoxia facilitated tumor progression, through a long-lasting memory that provides advantages for CTCs during the metastatic cascade.Significance:We revealed a novel hypoxic memory of prolonged suppression of tumor intrinsic type I IFN and AP signals that promote tumorigenesis and metastasis, suggesting novel mechanistic understanding of the immune evasive properties of CTCs.
Foxd1 dependent induction of temporal retinal character is required for visual function
Authors: Hernández-Bejarano María , Gestri Gaia , Monfries Clinton , Tucker Lisa , Dragomir Elena I. , Bianco Isaac H. , Bovolenta Paola , Wilson Stephen W. , Cavodeassi Florencia 
Published: May 2022

AbstractAppropriate patterning of the retina during embryonic development is assumed to underlie the establishment of spatially localised specialisations that mediate the perception of specific visual features. For instance, in zebrafish, an area involved in high acuity vision (HAA) is thought to be present in the ventro-temporal retina. Here we show that the interplay of the transcription factor Rx3 with Fibroblast Growth Factor and Hedgehog signals, initiates and restricts foxd1 expression to the prospective temporal retina, initiating naso-temporal regionalisation of the retina. Abrogation of FoxD1 results in the loss of temporal and expansion of nasal retinal character, and consequent absence of the HAA. These structural defects correlate with severe visual defects as assessed in optokinetic and optomotor response assays. In contrast, optokinetic responses are unaffected in the opposite condition in which nasal retinal character is lost at the expense of expanded temporal character. Our study indicates that the establishment of temporal retinal character during early retinal development is required for the specification of the HAA, and suggests a prominent role of the temporal retina in controlling specific visual functions.Summary statementThis study provides a mechanistic link between eye patterning and the establishment of functionally distinct retinal regions and reveals the temporal retina preferentially controls specific aspects of visual function.
DNAscan2: a versatile, scalable, and user-friendly analysis pipeline for next-generation sequencing data
Authors: Marriott Heather , Kabiljo Renata , Khleifat Ahmad Al , Dobson Richard J , Al-Chalabi Ammar , Iacoangeli Alfredo 
Published: May 2022

AbstractThe current widespread adoption of next-generation sequencing (NGS) in all branches of basic and clinical genetics fields means that users with highly variable informatics skills, computing facilities and application purposes need to process, analyse, and interpret NGS data. In this landscape, versatility, scalability, and user-friendliness are key characteristics for an NGS analysis tool. We developed DNAscan2, a highly flexible, end-to-end pipeline for the analysis of NGS data, which (i) can be used for the detection of multiple variant types, including SNVs, small indels, transposable elements, short tandem repeats and other large structural variants; (ii) covers all steps of the analysis, from quality control of raw data to the generation of html reports for the interpretation and prioritisation of results; (iii) is highly adaptable and scalable as it can be deployed and run via either a graphic user interface for non-bioinformaticians, a command line tool for personal computer usage, or as a Snakemake workflow that facilitates parallel multi-sample execution for high-performance computing environments; (iv) is computationally efficient by minimising RAM and CPU time requirements.Availability and ImplementationDNAscan2 is implemented in Python3 and is available to download as a command-line tool and graphical-user interface at https://github.com/KHP-Informatics/DNAscanv2 or a Snakemake workflow at https://github.com/KHP-Informatics/DNAscanv2_snakemake.
The wild life of ticks: using passive surveillance to determine the distribution and wildlife host range of ticks and the exoticHaemaphysalis longicornis, 2010-2021
Authors: Thompson Alec T. , White Seth A. , Doub Emily E. , Sharma Prisha , Frierson Kenna , Dominguez Kristen , Shaw David , Weaver Dustin , Vigil Stacey L. , Ruder Mark G. , Yabsley Michael J. 
Published: May 2022

AbstractBackgroundWe conducted a large-scale, passive regional survey of ticks associated with wildlife of the eastern U.S. Our primary goals were to better assess the current geographic distribution of exoticH. longicornisand to identify potential wild mammalian and avian host species. However, this large-scale survey also provided valuable information regarding the distribution and host associations for many other important tick species that utilize wildlife as hosts.MethodsTicks were opportunistically collected by cooperating state and federal wildlife agencies. All ticks were placed in the supplied vials and host information was recorded, including host species, age, sex, examination date, location (at least county and state), and estimated tick burden were recorded. All ticks were identified to species using morphology, suspectH. longicorniswere confirmed through molecular techniques.ResultsIn total, 1,940 hosts were examined from across 369 counties from 23 states in the eastern U.S. From these submissions, 20,626 ticks were collected and identified belonging to 11 different species. Our passive surveillance efforts detected exoticH. longicornisfrom nine host species from eight states. Notably, some of the earliest detections ofH. longicornisin the U.S. were collected from wildlife through this passive surveillance network. In addition, numerous new county reports were generated forAmblyomma americanum, A. maculatum, Dermacentor albipictus, D. variabilis, andIxodes scapularis.ConclusionsThis study provided data on ticks collected from animals from 23 different states in the eastern U.S. between 2010 – 2021 with the primary goal of better characterizing the distribution and host-associations of the exotic tickH. longicornis; however new distribution data on tick species of veterinary or medical importance was also obtained. Collectively, our passive surveillance has detected numerous new county reports forH. longicornisas well asI. scapularis. Our study utilizing passive wildlife surveillance for ticks across the eastern U.S. is an effective method for surveying a diversity of wildlife host species allowing us to better collect widespread data on current tick distributions relevant to human and animal health.
Cell-autonomous immune dysfunction driven by disrupted autophagy in C9orf72-ALS iPSC-derived microglia contributes to neurodegeneration
Authors: Banerjee Poulomi , Mehta Arpan R , Nirujogi Raja S , Cooper James , James Owen G , Nanda Jyoti , Longden James , Burr Karen , Salzinger Andrea , Paza Evdokia , Newton Judith , Story David , Pal Suvankar , Smith Colin , Alessi Dario R , Selvaraj Bhuvaneish T , Priller Josef , Chandran Siddharthan 
Published: May 2022

AbstractThe most common genetic mutation found in familial and sporadic amyotrophic lateral sclerosis (ALS), as well as fronto-temporal dementia (FTD), is a repeat expansion in the C9orf72 gene. C9orf72 is highly expressed in human myeloid cells, and although neuroinflammation and microglial pathology are widely found in ALS/FTD, the underlying mechanisms are poorly understood. Here, using human induced pluripotent stem cell-derived microglia-like cells (hiPSC-MG) harbouring C9orf72 mutation (mC9-MG) together with gene-corrected isogenic controls (isoC9-MG) and C9ORF72 knock-out hiPSC-MG (C9KO-MG), we show that reduced C9ORF72 protein is associated with impaired phagocytosis and an exaggerated inflammatory response upon stimulation with lipopolysaccharide, driven by sustained activation of NLRP3 inflammasome and NF-κB signalling. Analysis of the hiPSC-MG C9ORF72 interactome revealed an association of C9ORF72 with key regulators of autophagy, a process involved in the homeostatic regulation of the innate immune response. We found impaired initiation of autophagy in C9KO-MG and mC9-MG. Furthermore, through motor neuron-microglial (MN-MG) co-culture studies, we identified that autophagy deficit in mC9-MG led to increased vulnerability of C9 MNs to excitotoxic stimulus. Pharmacological activation of autophagy ameliorated the sustained activation of NLRP3 inflammasome and NF-κB signalling, reversed the phagocytic deficit found in mC9-MG and also reduced MN death in MN-MG co-cultures. We validated these findings in blood-derived macrophages from people with C9orf72 mutation. Our results reveal an important role for C9ORF72 in regulating microglial immune homeostasis and identify dysregulation in human myeloid cells as a contributor to neurodegeneration in ALS/FTD.TeaserDisrupted autophagy led immune activation in microglia results in enhanced motor neuronal death in C9orf72-ALS.
Systemic pesticides in a solitary bee pollen food store affect larval development and increase pupal mortality
Authors: Phan Ngoc T. , Joshi Neelendra K. , Rajotte Edwin G. , Zhu Fang , Peter Kari A. , López-Uribe Margarita M. , Biddinger David J. 
Published: May 2022

SummarySolitary bees are often exposed to various pesticides applied for pest control on farmland while providing pollination services to food crops1. Increasing evidence suggests that sublethal toxicity of agricultural pesticides affects solitary bees differently than the social bees used to determine regulatory thresholds like honey bees and bumblebees2–4. Studies on solitary bees are challenging because of the difficulties in obtaining large numbers of eggs or young larvae for bioassays. Here we show the toxic and sublethal developmental effects of four widely used plant systemic pesticides on the Japanese orchard bee (Osmia cornifrons). Pollen food stores of this solitary bee were treated with different concentrations of three insecticides (acetamiprid, flonicamid, and sulfoxaflor) and a fungicide (dodine). Eggs were transplanted to the treated pollen and larvae were allowed to feed on the pollen stores after egg hatch. The effects of chronic ingestion of contaminated pollen were measured until adult eclosion. This year-long study revealed that chronic exposure to all tested pesticides delayed larval development and lowered larval and adult body weights. Additionally, exposure to the systemic fungicide resulted in abnormal larval defecation and increased mortality at the pupal stage, indicating potential risk to bees from fungicide exposure. These findings demonstrate potential threats to solitary bees from systemic insecticides and fungicides and will help making policy decisions for mitigating these effects.
Mesenchymal Stromal Cells Donate Mitochondria to Articular Chondrocytes Exposed to Mitochondrial, Environmental, and Mechanical Stress
Authors: Fahey Megan J. , Bennett Maureen P. , Thomas Matthew , Vivancos-Koopman Irene , Browning Lindsay , Bonassar Lawrence J. , Delco Michelle L. 
Published: May 2022

AbstractAvascular soft tissues of the skeletal system, including articular cartilage, have limited healing capacity, in part due to their low metabolic activity. No drugs are available that can prevent or slow the development of osteoarthritis (OA) after joint injury. Therefore, mesenchymal stromal cell (MSC)-based regenerative therapies are increasingly common in the treatment of OA, but questions regarding their clinical efficacy and mechanisms of action remain unanswered. Our group recently reported that mitochondrial dysfunction is one of the earliest responses of cartilage to injury, resulting in chondrocyte death, extracellular matrix degeneration, and ultimately OA. MSCs have been found to rescue injured cells and improve healing by donating healthy mitochondria in highly metabolic tissues, but mitochondrial transfer has not been investigated in cartilage. Here, we demonstrate that MSCs transfer mitochondria to stressed chondrocytes in cell culture and in injured cartilage tissue. Conditions known induce chondrocyte mitochondrial dysfunction, including stimulation with rotenone/antimycin and hyperoxia, increased transfer. Stressed chondrocytes increased expression of genes related to inflammation and senescence, further supporting the link between mitochondrial dysfunction and transfer. MSC-chondrocyte mitochondrial transfer was blocked by non-specific and specific (connexin-43) gap-junction inhibition. When MSCs were exposed to mechanically injured cartilage they localized to areas of matrix damage and extended cellular processes deep into microcracks, delivering mitochondria to chondrocytes. This work provides insights into the chemical, environmental, and mechanical conditions that can elicit MSC-chondrocyte mitochondrial transfer in vitro and in situ, and our findings suggest a new potential role for MSC-based therapeutics after cartilage injury.Significance StatementRecent evidence suggests that although articular cartilage is avascular and relatively metabolically quiescent, acute injury induces chondrocyte mitochondrial dysfunction, driving cartilage degradation and OA. We present the first evidence that MSCs donate mitochondria to articular chondrocytes undergoing mitochondrial dysfunction in vitro and in situ. These findings support a new role for MSCs in the context of cartilage injury and OA, and intercellular mitochondrial transfer may represent a new biological approach to augment mitochondrial capacity in injured chondrocytes. This work establishes multiple experimental models to study MSC mitochondrial donation for the treatment of OA and related degenerative diseases of avascular orthopedic tissues.
petiteFinder: An automated computer vision tool to compute Petite colony frequencies in baker’s yeast
Authors: Nunn Christopher J. , Klyshko Eugene 
Published: May 2022

AbstractMitochondrial respiration is central to cellular and organismal health in eukaryotes. In baker’s yeast, however, respiration is dispensable under fermentation conditions. Because yeast are tolerant of this mitochondrial dysfunction, yeast are widely used by biologists as a model organism to ask a variety of questions about the integrity of mitochondrial respiration. Fortunately, baker’s yeast also display a visually identifiable Petite colony phenotype that indicates when cells are incapable of respiration. Petite colonies are smaller than their Grande (wild-type) counterparts, and their frequency can be used to infer the integrity of mitochondrial respiration in populations of cells. In this study, we introduce a deep learning enabled tool,petiteFinder, to leverage the Petite colony phenotype and increase the throughput of the Petite frequency assay. This automated computer vision tool detects Grande and Petite colonies and computes Petite colony frequencies from scanned images of Petri dishes. It addresses issues in scalability and reproducibility of the Petite colony assay which currently relies on laborious manual colony counting methods. Combined with the detailed experimental protocols we provide, we believe this study can serve as a foundation to standardize this assay. Finally, we comment on how Petite colony detection as a computer vision problem highlights ongoing difficulties with small object detection in existing object detection architectures.