bluuebunny/crossref_metadata_2025_split huggingface dataset:
The protein modifier SUMO is critical for Arabidopsis shoot meristem maintenance at warmer ambient temperatures
Authors: Hammoudi Valentin , Beerens Bas , Jonker Martijs J. , Helderman Tieme A. , Vlachakis Georgios , Giesbers Marcel , Kwaaitaal Mark , van den Burg Harrold A. 
Published: February 2021

AbstractShort heat waves (>37°C) are extremely damaging to non-acclimated plants and their capacity to recover from heat stress is key for their survival. To acclimate, the HEAT SHOCK TRANSCRIPTION FACTOR A1 (HSFA1) subfamily activates a transcriptional response that resolves incurred damages. In contrast, little is known how plants acclimate to sustained non-detrimental warm periods at 27-28°C. Plants respond to this condition with a thermomorphogenesis response. In addition, HSFA1 is critical for plant survival during these warm periods. We find that SUMO, a protein modification whose conjugate levels rise sharply during acute heat stress in eukaryotes, is critical too for plant longevity during warm periods, in particular for normal shoot meristem development. The known SUMO ligases were not essential to endure these warm periods, alone or in combination. Thermo-lethality was also not seen when plants lacked certain SUMO proteases or when SUMO chain formation was blocked. The SUMO-dependent thermo-resilience was as well independent of the autoimmune phenotype of the SUMO mutants. As acquired thermotolerance was normal in thesumo1/2knockdown mutant, our data thus reveal a role for SUMO in heat acclimation that differs from HSFA1 and SIZ1. We conclude that SUMO is critical for shoot meristem integrity during warm periods.HighlightThe protein modifier SUMO governs shoot meristem maintenance in Arabidopsis allowing sustained rosette development when plants endure a sustained warm non-detrimental period of 28 degrees Celsius.
Genomic regions associated withMycoplasma ovipneumoniaepresence in nasal secretions of domestic sheep
Authors: Mousel Michelle R. , White Stephen N. , Herndon Maria K. , Herndon David R. , Taylor J. Bret , Becker Gabrielle M. , Murdoch Brenda M. 
Published: February 2021

AbstractMycoplasma ovipneumoniaecontributes to polymicrobial pneumonia in domestic sheep. Elucidation of host genetic components toM. ovipneumoniaenasal detection would have the potential to reduce the incidence of pneumonia. Nasal mucosal secretions were collected from 647 sheep from a large US sheep flock. Ewes of three breeds (Polypay n=222, Rambouillet n=321, and Suffolk n=104) ranging in age from one to seven years, were sampled at three different times of the production cycle (February, April, and September/October) over four years (2015 to 2018). The presence and quantity ofM. ovipneumoniaewas determined using a species-specific qPCR with 3 to 10 sampling times per sheep. Breed (P<0.001), age (P<0.024), sampling time (P<0.001), and year (P<0.001) of collection affected log10transformedM. ovipneumoniaeDNA copy number, where Rambouillet had the lowest (P<0.0001) compared with both Polypay and Suffolk demonstrating a possible genetic component to detection. Samples from yearlings, April, and 2018 had the highest (P<0.046) detected DNA copy number mean. Sheep genomic DNA was genotyped with the Illumina OvineHD BeadChip. Principal component analysis identified most of the variation in the dataset was associated with breed. Therefore, genome wide association analysis was conducted with a mixed model (EMMAX), with principle components 1 to 6 as fixed and a kinship matrix as random effects. Genome-wide significant (P<9×10−8) SNPs were identified on chromosomes 6 and 7 in the all-breed analysis. Individual breed analysis had genome-wide significant (P<9×10−8) SNPs on chromosomes 3, 4, 7, 9, 10, 15, 17, and 22. Annotated genes near these SNPs are part of immune (ANAPC7, CUL5, TMEM229B, PTPN13), gene translation (PIWIL4), and chromatin organization (KDM2B) pathways. Immune genes are expected to have increased expression when leukocytes encounterM. ovipneumoniaewhich would lead to chromatin reorganization. Work is underway to narrow the range of these associated regions to identify the underlying causal mutations.
AlnC: An extensive database of long non-coding RNAs in Angiosperms
Authors: Singh Ajeet , Vivek AT , Kumar Shailesh 
Published: February 2021

AbstractLong non-coding RNAs (lncRNAs) play a major role in diverse biological processes that are contemplated to have diverse regulatory roles in plants. While lncRNAs have been described and annotated in major plant species, many of plant species lack annotated lncRNAs despite the availability of transcriptome data in public repositories. In this study, we have identified and annotated the lncRNAs in the transcriptomic data from the 1000 plant genome project (1KP), and developed a user-friendly, open-access database called AlnC. This can be used for the exploration of lncRNAs in 682 Angiosperm plants. The current version of AlnC offers 10,855,598 annotated lncRNA transcripts across 809 sample tissues of diverse flowering plants. To enhance the AlnC interface, we have provided the features for browsing, searching and downloading of lncRNA data, interactive graphics, and online BLAST service. In addition to these information, each lncRNA record is annotated with possible Short open reading frames (e.g. sORFs) to facilitate the study of peptides encoded within lncRNAs. With this user-friendly interface, we assume that AlnC will serve as a rich source of lncRNAs that will contribute to small-and large-scale studies in a wide range of flowering plants.
Limitations of bacterial culture, viral PCR, and tulathromycin susceptibility test methods from upper respiratory tract samples in predicting the outcome of tulathromycin control or treatment of bovine respiratory disease in high risk feeder heifers
Authors: Sarchet Jeffrey J. , Pollreisz John H. , Bechtol David T. , Blanding Mitch , Saltman Roger L. , Taube Patrick C. 
Published: February 2021

AbstractA cross-sectional prospective cohort study to correlate BRD clinical outcomes for tulathromycin metaphylaxis/treatment for bovine respiratory disease (BRD) with the results of bacterial culture and tulathromycin susceptibility from isolates of deep nasopharyngeal swabs (DNS) as well as viral polymerase chain reaction (PCR) results from nasal swabs revealed poor correlation of bacterial culture and tulathromycin susceptibility with response to tulathromycin metaphylaxis or treatment. 1031 heifers, assumed to be at high-risk (>40% expected BRD morbidity rates), were procured and transported to a research feedlot in Texas. Isolation rates from DNS collected on arrival and at first treatment respectively were:Mannheimia haemolytica(10.9% & 34.1%);Pasteurella multocida(10.4% & 7.4%);Mycoplasma bovis(1.0% & 36.6%); andHistophilus somni (0.7% & 6.3%). Prevalence of BRD viral nucleic acid on nasal swabs collected at first treatment were: PI-3V (34.1%); BVDV (26.3%); BoHV-1 (10.8%); and BRSV (54.1%). Increased relative risk of treatment failure was associated with positive viral PCR results, PI-3V (1.2644), BVDV (1.3917), BHV-1 (1.5156), and BRSV (1.3474) from nasal swabs collected at first pull and culture ofM. haemolytica(1.2284) from DNS collected at arrival; however, no other statistically predictable risk of treatment outcomes were measured from DNS for bacterial isolation or tulathromycin susceptibility forM. haemolyticaorP. multocidaat arrival or first treatment. Predictive values of bacterial culture and tulathromycin susceptibility were substantially lower than the 85% level expected with susceptibility testing. These results indicate tulathromycin susceptibility testing of isolates ofM. haemolyticaorP. multocidafrom DNS collected on arrival or at first pull unreliably predict clinical efficacy of tulathromycin for BRD control or treatment most likely due to impacts of unpredictable risk factors and other viral and/or bacterial BRD comorbidities.
ATP-dependent Clp protease subunit C1, HvClpC1, is a strong candidate gene for barley variegation mutantluteostriansas revealed by genetic mapping and genomic re-sequencing
Authors: Li Mingjiu , Guo Ganggang , Pidon Hélène , Melzer Michael , Prina Alberto R. , Börner Thomas , Stein Nils 
Published: February 2021

AbstractImplementation of next-generation sequencing in forward genetic screens greatly accelerated gene discovery in species with larger genomes, including many crop plants. In barley, extensive mutant collections are available, however, the causative mutations for many of the genes remains largely unknown. Here we demonstrate how a combination of low-resolution genetic mapping, whole-genome resequencing and comparative functional analyses provides a promising path towards candidate identification of genes involved in plastid biology and / or photosynthesis, even if genes are located in recombination poor regions of the genome. As a proof of concept, we simulated the prediction of a candidate gene for the recently cloned variegation mutantalbostrians(HvAST/HvCMF7) and adopted the approach for suggestingHvClpC1as candidate gene for the yellow-green variegation mutantluteostrians.Author SummaryForward genetics is an approach of identifying a causal gene for a mutant phenotype and has proven to be a powerful tool for dissecting the genetic control of biological processes in many species. A large number of barley mutants was generated in the 1940s to 1970s when mutation breeding programs flourished. Genetic dissection of the causative mutations responsible for the phenotype, however, lagged far behind, limited by lack of molecular markers and high-throughput genotyping platforms. Next-generation sequencing technologies have revolutionized genomics, facilitating the process of identifying mutations underlying a phenotype of interest. Multiple mapping-by-sequencing or cloning-by-sequencing strategies were established towards fast gene discovery. In this study, we used mapping-by-sequencing to identify candidate genes within coarsely delimited genetic intervals, for two variegation mutants in barley –luteostriansandalbostrians. After testing the approach using the example of the previously clonedalbostriansgeneHvAST, the geneHvClpC1could be delimited as candidate gene forluteostrians.The mapping-by-sequencing strategy implemented here is generally suited for surveying barley mutant collections for phenotypes affecting fundamental processes of plant morphology, physiology and development.
Genome-Wide CRISPR Screening Identifies BRD9 as a Druggable Component of Interferon-Stimulated Gene Expression and Antiviral Activity
Authors: Börold Jacob , Eletto Davide , Busnadiego Idoia , Mair Nina K. , Moritz Eva , Schiefer Samira , Schmidt Nora , Petric Philipp P. , Wong W. Wei-Lynn , Schwemmle Martin , Hale Benjamin G. 
Published: February 2021

ABSTRACTTransient interferon (IFN) induction of IFN-stimulated genes (ISGs) creates a formidable protective antiviral state. However, loss of appropriate control mechanisms can result in constitutive pathogenic ISG upregulation. Here, we used genome-wide loss-of-function screening to establish genes critical for IFN signaling, identifying all expected members of the JAK-STAT pathway and the previously unappreciated bromodomain-containing protein 9 (BRD9), a defining subunit of non-canonical BAF (ncBAF) chromatin remodeling complexes. Genetic knock-out or small-molecule mediated degradation of BRD9 limited IFN-induced expression of a subset of ISGs in multiple cell-types, and prevented IFN from exerting full antiviral activity against several RNA and DNA viruses. Mechanistically, BRD9 acts at the level of ISG transcription, exhibits a proximal association with STAT2 following IFN stimulation, and relies on its intact acetyl-binding bromodomain and unique ncBAF scaffolding function for activity. Given its druggability, BRD9 may be an attractive target for dampening constitutive ISG expression under certain pathogenic autoinflammatory conditions.
Microglia control cerebral blood flow and neurovascular coupling via P2Y12R-mediated actions
Authors: Császár Eszter , Lénárt Nikolett , Cserép Csaba , Környei Zsuzsanna , Fekete Rebeka , Pósfai Balázs , Balázsfi Diána , Hangya Balázs , Schwarcz Anett D. , Szöllősi Dávid , Szigeti Krisztián , Máthé Domokos , West Brian L. , Sviatkó Katalin , Brás Ana Rita , Mariani Jean-Charles , Kliewer Andrea , Lenkei Zsolt , Hricisák László , Benyó Zoltán , Baranyi Mária , Sperlágh Beáta , Menyhárt Ákos , Farkas Eszter , Dénes Ádám 
Published: February 2021

AbstractMicroglia, the main immunocompetent cells of the brain regulate neuronal function in health and disease, but their contribution to cerebral blood flow (CBF) remained elusive. Here we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. We show that microglia establish direct purinergic contacts with cells in the neurovascular unit that shape cerebral perfusion in both mice and humans. Surprisingly, the absence of microglia or blockade of microglial P2Y12 receptor (P2Y12R) substantially impairs neurovascular coupling in the barrel cortex after whisker stimulation. We also reveal that hypercapnia, which is associated with acidification, induces microglial adenosine production, while depletion of microglia reduces brain pH and impairs hypercapnia-induced vasodilation. Furthermore, the absence or dysfunction of microglia markedly impairs adaptation to hypoperfusion via P2Y12R after transient unilateral common carotid artery occlusion, which is also influenced by CX3CR1-mediated actions. Thus, our data reveal a previously unrecognized role for microglia in CBF regulation with broad implications for common neurological diseases.
Alpha-arrestins Aly1 and Aly2 regulate trafficking of the glycerophosphoinositol transporter Git1 and impact phospholipid homeostasis
Authors: Robinson Benjamin P. , Hawbaker Sarah , Chiang Annette , Jordahl Eric M. , Anaokar Sanket , Nikiforov Alexiy , Bowman Ray W. , Ziegler Philip , McAtee Ceara K. , Patton-Vogt Jana , O’Donnell Allyson F. 
Published: February 2021

AbstractPhosphatidylinositol (PI) is an essential phospholipid and critical component of membrane bilayers. The complete deacylation of PI by phospholipases of the B-type leads to the production of intracellular and extracellular glycerophosphoinositol (GPI), a water-soluble glycerophosphodiester. Extracellular GPI is transported into the cell via Git1, a member of the Major Facilitator Superfamily of transporters that resides at the plasma membrane in yeast. Once internalized, GPI can be degraded to produce inositol, phosphate and glycerol, thereby contributing to reserves of these building blocks. Not surprisingly,GIT1gene expression is controlled by nutrient balance, with limitation for phosphate or inositol each increasingGIT1expression to facilitate GPI uptake. Less is known about how Git1 protein levels or localization are controlled. Here we show that the α-arrestins, an important class of protein trafficking adaptor, regulate the localization of Git1 in a manner dependent upon their association with the ubiquitin ligase Rsp5. Specifically, α-arrestin Aly2 is needed for effective Git1 internalization from the plasma membrane under basal conditions. However, in response to GPI-treatment of cells, either Aly1 or Aly2 can promote Git1 trafficking to the vacuole. Retention of Git1 at the cell surface, as occurs inaly1Δaly2Δ cells, results in impaired growth in the presences of excess exogenous GPI and results in increased uptake of radiolabeled GPI, suggesting that accumulation of this metabolite or its downstream products leads to cellular toxicity. We further show that regulation of α-arrestin Aly1 by the protein phosphatase calcineurin improves both steady-state and ligand-induced trafficking of Git1 when a mutant allele of Aly1 that mimics the dephosphorylated state at calcineurin-regulated residues is employed. Thus, calcineurin regulation of Aly1 is important for the GPI-ligand induced trafficking of Git1 by this α-arrestin, however, the role of calcineurin in regulating Git1 trafficking is much broader than can simply be explained by regulation of the α-arrestins. Finally, we find that loss of Aly1 and Aly2 leads to an increase in phosphatidylinositol-3-phosphate on the limiting membrane of the vacuole and this alteration is further exacerbated by addition of GPI, suggesting that the effect is at least partially linked to Git1 function. Indeed, loss of Aly1 and Aly2 leads to increased incorporation of inositol label from3H-inositol-labelled GPI into PI, confirming that internalized GPI influences PI synthesis and indicating a role for the α-arrestins in regulating the process.
Bronchoalveolar lavage affects thorax computed tomography of healthy and SARS-CoV-2 infected rhesus macaques (Macaca mulatta)
Authors: Maaskant Annemiek , Meijer Lisette , Bakker Jaco , van Geest Leo , Zijlmans Dian G.M. , Langermans Jan A.M. , Verschoor Ernst J. , Stammes Marieke A. 
Published: February 2021

AbstractMedical imaging as method to assess the longitudinal process of a SARS-CoV-2 infection in non-human primates is commonly used in research settings. Bronchoalveolar lavage (BAL) is also regularly used to determine the local virus production and immune effects of SARS-CoV-2 in the lower respiratory tract. However, the potential interference of those two diagnostic modalities with each other is unknown in non-human primates. The current study investigated the effect and duration of BAL on computed tomography (CT) in both healthy and experimentally SARS-CoV-2-infected female rhesus macaques (Macaca mulatta). In addition, the effect of subsequent BALs was reviewed. Thorax CTs and BALs were obtained from four healthy animals and 11 experimentally SARS-CoV-2-infected animals. From all animals, CTs were obtained just before BAL, and 24 hours post-BAL. Additionally, from the healthy animals, CTs immediately after and four hours post-BAL were obtained. Thorax CTs were evaluated for alterations in lung density, measured in Hounsfield units, and a visual semi-quantitative scoring system. An increase in the lung density was observed on the immediately post-BAL CT but resolved within 24 hours in the healthy animals. In the infected animals, a significant difference in both the lung density and CT score was still found 24 hours after BAL. Furthermore, the differences between timepoints in CT score were increased for the second BAL. These results indicate that the effect of BAL on infected lungs is not completed within the first 24 hours. Therefore, it is of importance to acknowledge the interference between BAL and CT in rhesus macaques.
Modulation of SARS-CoV-2 Spike-induced Unfolded Protein Response (UPR) in HEK293T cells by selected small chemical molecules
Authors: Balakrishnan B , Lai K 
Published: February 2021

AbstractCoronaviruses (CoV) exploits the endoplasmic reticulum (ER) of the host cells for replication and in doing so, increases ER stress. evokes Unfolded Protein Response (UPR) and possibly autophagy, which could all attribute to the pathophysiology of the viral infections. To date, little is known about the roles of ER stress, UPR, and autophagy in SARS-CoV-2 infection. Here we over-expressed the viral Spike (S) protein in cultured HEK293T cells, as it has been shown that such protein is largely responsible for UPR activation in other CoV-infected cells. We noticed, in the transfected cells, heightened ER stress, activation of the PERK-eIF2α arm of the UPR, induction of autophagy and cell death. When we treated the transfected cells with Tauroursodeoxycholic acid (TUDCA), 4-phenyl butyric acid (PBA), Salubrinal, Trazadone hydrochloride, and Dibenzoylmethane (DBM), we saw reduced the BiP/GRP78 levels, but only PBA and TUDCA could significantly diminish the levels of peIF2α and autophagy expression.
Ventral hippocampus mediates the context-dependence of two-way signaled avoidance in male rats
Authors: Oleksiak Cecily R. , Ramanathan Karthik R. , Miles Olivia W. , Perry Sarah J. , Maren Stephen , Moscarello Justin M. 
Published: February 2021

AbstractConsiderable work indicates that instrumental responding is context-dependent, but the neural mechanisms underlying this phenomenon are poorly understood. Given the important role for the hippocampal formation in contextual processing, we hypothesized that reversible inactivation of the hippocampus would impair the context-dependence of active avoidance. To test this hypothesis, we used a two-way signaled active avoidance (SAA) task that requires rats to shuttle across a divided chamber during a tone CS in order to avoid a footshock US. After training, avoidance responding was assessed in an extinction test in both the training context and a novel context in a counterbalanced order. Rats performed significantly more avoidance responses in the training context than in the novel context, demonstrating the context-dependence of shuttle avoidance behavior. To examine the role of the hippocampus in the context-dependence of SAA, we reversibly inactivated either the dorsal (DH) or ventral hippocampus (VH) prior to testing. Inactivation of the VH eliminated the context-dependence of SAA and elevated avoidance responding in the novel context to levels similar to that expressed in the training context. In contrast, DH inactivation had no effect on avoidance in either context, and neither manipulation affected freezing behavior. Therefore, the integrity of the VH, but not DH, is required for the expression context-dependence of avoidance behavior.
High Affinity Chimeric Antigen Receptor with Cross-Reactive scFv to Clinically Relevant EGFR Oncogenic Isoforms
Authors: Thokala Radhika , Binder Zev A. , Yin Yibo , Zhang Logan , Zhang Jiasi Vicky , Zhang Daniel Y. , Milone Michael C. , Ming Guo-li , Song Hongjun , O’Rourke Donald M. 
Published: February 2021

AbstractTumor heterogeneity is a key reason for therapeutic failure and tumor recurrence in glioblastoma (GBM). Our chimeric antigen receptor (CAR) T cell (2173 CAR T cells) clinical trial (NCT02209376) against Epidermal growth factor receptor (EGFR) variant III (EGFRvIII) demonstrated successful trafficking of T cells across the blood brain barrier into GBM active tumor sites. However, CAR T cell infiltration was associated only with a selective loss of EGFRvIII+ tumor, demonstrating little to no effect on EGFRvIII-tumor cells. Post-CAR T treated tumor specimens showed continued presence of EGFR amplification and oncogenic EGFR extracellular domain (ECD) missense mutations, despite loss of EGFRvIII. To address tumor escape, we generated an EGFR-specific CAR by fusing monoclonal antibody (mAb) 806 to a 4-1BB co-stimulatory domain. The resulting construct was compared to 2173 CAR T cells in GBM, using in vitro and in vivo models. 806 CAR T cells specifically lysed tumor cells and secreted cytokines in response to amplified EGFR, EGFRvIII, and EGFR-ECD mutations in U87MG cells, GBM neurosphere-derived cell lines, and patient-derived GBM organoids. 806 CAR T cells did not lyse fetal brain astrocytes or primary keratinocytes to a significant degree. They also exhibited superior antitumor activity in vivo when compared to 2173 CAR T cells. The broad specificity of 806 CAR T cells to EGFR alterations gives us the potential to target multiple clones within a tumor and reduce opportunities for tumor escape via antigen loss.