bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adolescent Stress Confers Resilience to Traumatic Stress Later in Life: Role of the Prefrontal Cortex
Authors: Cotella E.M. , Nawreen N , Moloney R.D. , Martelle S.E. , Oshima K.M. , Lemen P. , NiBlack J. N. , Julakanti R. R. , Fitzgerald M. , Baccei M.L. , Herman J.P. 
Published: March 2021

ABSTRACTStress during adolescence is usually associated with psychopathology later in life. However, under certain circumstances, developmental stress can promote an adaptive phenotype, allowing individuals to cope better with adverse situations in adulthood, thereby contributing to resilience. The aim of the study was to understand how adolescent stress alters behavioral and physiological responses to traumatic stress in adulthood. Sprague Dawley rats were subjected to adolescent chronic variable stress (adol CVS) followed by single prolonged stress (SPS) in adulthood. One week after SPS, animals were tested for acquisition, extinction, extinction recall and reinstatement of auditory-cued fear conditioning, with neuronal recruitment during reinstatement assessed by Fos expression. Patch clamp electrophysiology was performed to examine physiological changes associated with resilience. We observed that adol CVS blocked SPS-induced impairment of extinction learning (males) and enhancement fear reinstatement (both sexes). SPS effects were associated with a reduction of infralimbic (IL) cortex neuronal recruitment after reinstatement in males and increased engagement of the central amygdala in females, both of which were also prevented by adol CVS. We explored the mechanism behind reduced IL recruitment in male rats by studying the intrinsic excitability of IL pyramidal neurons. SPS reduced excitability of IL neurons and prior adol CVS prevented this effect, indicating that adolescent stress can impart resilience to the effects of traumatic stress by modification of IL output in males. Overall, our study suggests that prior stress exposure can limit the impact of a subsequent severe stress exposure in adulthood, effects that are mediated by sex-specific modification of infralimbic and amygdala signaling.
The arrested state of processing bodies supports mRNA regulation in early development
Authors: Sankaranarayanan M. , Emenecker Ryan J. , Jahnel Marcus , Trussina Irmela R. E. A. , Wayland Matt , Alberti Simon , Holehouse Alex S. , Weil Timothy T. 
Published: March 2021

ABSTRACTBiomolecular condensates that form via liquid-liquid phase separation can exhibit diverse physical states. Despite considerable progress, the relevance of condensate physical states forin vivobiological function remains limited. Here, we investigated the physical properties ofin vivoprocessing bodies (P bodies) and their impact on mRNA storage in matureDrosophilaoocytes. We show that the conserved DEAD-box RNA helicase Me31B forms P body condensates which adopt a less dynamic, arrested physical state. We demonstrate that structurally distinct proteins and hydrophobic and electrostatic interactions, together with RNA and intrinsically disordered regions, regulate the physical properties of P bodies. Finally, using live imaging, we show that the arrested state of P bodies is required to prevent the premature release ofbicoid(bcd) mRNA, a body axis determinant, and that P body dissolution leads tobcdrelease. Together, this work establishes a role for arrested states of biomolecular condensates in regulating cellular function in a developing organism.
B cells imprint adoptively transferred CD8+T cells with enhanced tumor immunity
Authors: Smith Aubrey S. , Knochelmann Hannah M. , Wyatt Megan M. , Rivera Guillermo O. Rangel , Rivera-Reyes Amalia M. , Dwyer Connor J. , Neskey David M. , Rubinstein Mark P. , Liu Bei , Thaxton Jessica E. , Bartee Eric , Paulos Chrystal M. 
Published: March 2021

ABSTRACTHere we report a novel strategy to reverse the tolerant state of adoptively transferred CD8+T cells against melanoma throughex vivoexpansion with the TLR9 agonist CpG. T cells generated in the presence of CpG display potent anti-tumor efficacy withoutin vivoco-administration of high dose IL-2 or vaccination, which are classically required for effective treatment of solid tumors using adoptive cell therapies. CD8+T cells adopt a unique proteomic signature and are characterized by an IL-2RαhighICOShighCD39lowphenotype after CpG-mediated expansion. Surprisingly, we found that the presence of B cells, in the culture, was essential for imprinting CD8+T cells with this phenotype and moreover purified B cells were sufficient to mediate the CpG-associated changes in T cells. These findings reveal a vital role for B cells in the generation of effective antitumor CD8+T cells and have immediate implications for profoundly improving immunotherapy for patients.SUMMARY STATEMENTThe TLR9 agonist CpG allows B cells to license adoptively transferred CD8+ T cells with potent tumor immunity. These licensed T cells have a unique proteomic signature, are marked by low CD39 and high ICOS and IL-2Rα expression, and engraft robustlyin vivo.
An inconvenient association between granzyme A and Nicotinamide Nucleotide Transhydrogenase
Authors: Rawle Daniel J. , Le Thuy T. , Dumenil Troy , Bishop Cameron , Yan Kexin , Nakayama Eri , Bird Phillip I. , Suhrbier Andreas 
Published: March 2021

ABSTRACTGranzyme A (GzmA) is a serine protease secreted by cytotoxic lymphocytes, with GzmA-/-mouse studies informing our understanding of GzmA’s physiological function. We show herein that GzmA-/-mice have a mixed C57BL/6J and C57BL/6N background and retain the full length Nicotinamide Nucleotide Transhydrogenase (Nnt) gene, whereasNntis truncated in C57BL/6J mice. Chikungunya viral arthritis was substantially ameliorated in GzmA-/-mice; however, the presence ofNnt, rather than loss of GzmA, was responsible for this phenotype by constraining lymphocyte infiltration. A new CRISPR active site mutant C57BL/6J GzmAS211Amouse provided the first insights into GzmA’s bioactivity free of background issues, with circulating proteolytically active GzmA promoting immune-stimulating and pro-inflammatory signatures. Remarkably, k-mer mining of the Sequence Read Archive illustrated that ≈27% of Run Accessions and ≈38% of Bioprojects listing C57BL/6J as the mouse strain, hadNntsequencing reads inconsistent with a C57BL/6J background. TheNntissue has clearly complicated our understanding of GzmA and may similarly have influenced studies across a broad range of fields.
Structural analysis of the OC43 coronavirus 2′-O-RNA methyltransferase
Authors: Dostalik Pavel , Krafcikova Petra , Silhan Jan , Boura Evzen 
Published: March 2021

AbstractThe OC43 coronavirus is a human pathogen that usually causes only the common cold. One of its key enzymes, similar to other coronaviruses, is the 2′-O-RNA methyltransferase (MTase) that is essential for viral RNA stability and expression. Here, we report the crystal structure of the 2′-O-RNA MTase in a complex with the pan-methyltransferase inhibitor sinefungin solved at 2.2 Å resolution. The structure revealed an overall fold consistent with the fold observed in other coronaviral MTases. The major differences are in the conformation of the C-terminus of the nsp16 subunit and an additional helix in the N-terminus of the nsp10 subunits. The structural analysis also revealed very high conservation of the SAM binding pocket suggesting that the SAM pocket is a suitable spot for the design of antivirals effective against all human coronaviruses.ImportanceSome coronaviruses are dangerous pathogens while some cause only common colds. The reasons are not understood although the spike proteins probably play an important role. However, to understand the coronaviral biology in sufficient detail we need to compare the key enzymes from different coronaviruses. We solved the crystal structure of 2′-O-RNA methyltransferase of the OC43 coronavirus, a virus that usually causes mild colds. The structure revealed some differences in the overall fold but also revealed that the SAM binding site is conserved suggesting that development of antivirals against multiple coronaviruses is feasible.
B.1.1.7 became the dominant variant in Lebanon
Authors: Younes Mahmoud , Hamze Kassem , Carter Daniel P. , Osman Karen L. , Vipond Richard , Carroll Miles , Pullan Steven T. , Nassar Hassan , Mohamad Nada , Makki Mohamad , Ghadar Maysaa , Nguewa Paul , Sater Fadi Abdel 
Published: March 2021

ABSTRACTRecently, a new variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) designated VOC 202012/01 (or B.1.1.7 lineage) has become highly prevalent in several countries, after first being described in the United Kingdom (UK). Its rate of transmission has been estimated to be increased compared to other lineages. In the present study, we show the emergence, dominance and the rapid spread of the B.1.1.7 lineage in Lebanon.
Causal associations between fatty acid measures and schizophrenia – a two-sample Mendelian randomization study
Authors: Jones Hannah J , Borges Maria Carolina , Carnegie Rebecca , Mongan David , Rogers Peter J , Lewis Sarah J , Thompson Andrew D , Zammit Stanley 
Published: March 2021

AbstractObjectiveAlthough studies suggest that erythrocyte concentrations of omega-3 and omega-6 fatty acids are lower in individuals with schizophrenia, evidence of beneficial effects of omega-3 fatty acid supplementation is limited. This study therefore aimed to determine whether omega-3 and omega-6 fatty acid levels are causally related to schizophrenia.MethodsCausality was evaluated using the inverse variance weighted (IVW) 2-sample Mendelian randomization (MR) method using fatty acid levels and schizophrenia genome-wide association study results. Weighted median, weighted mode, and MR Egger regression methods were used as sensitivity analyses. To address the mechanism, analyses were performed using instruments within the FADS and ELOVL2 genes. Multivariable MR (MVMR) was used to estimate direct effects of omega-3 fatty acids on schizophrenia, independent of omega-6 fatty acids, lipoproteins and triglycerides.ResultsMR analyses indicated that long-chain omega-3 and omega-6 fatty acid levels were associated with lower risk of schizophrenia (docosahexaenoic acid [DHA] ORIVW: 0.83, 95% CI: 0.75-0.92). In contrast, short-chain fatty acids were associated with an increased risk of schizophrenia (alpha-linolenic acid ORIVW: 1.07, 95% CI: 0.98-1.18). Causal effects were consistent across sensitivity and FADS single-SNP analyses. MVMR indicated that the protective effect of DHA on schizophrenia persisted after conditioning on other lipids (ORIVW: 0.84, 95% CI: 0.71-1.01).ConclusionsResults are consistent with protective effects of long-chain omega-3 and omega-6 fatty acids on schizophrenia suggesting that people with schizophrenia may have difficulty converting short-chain to long-chain PUFAs. Long-chain PUFA supplementation or diet enrichment, particularly in higher risk individuals, might help prevent onset of disorder.
On the protective role of the blood vessels in glaucomatous damage: a transversal study
Authors: Cánovas-Serrano Yaiza , Vallés-San-Leandro Lorenzo , Rodríguez-Izquierdo Miguel Ángel , Lajara-Blesa Jerónimo , López-Serrano Rafael 
Published: March 2021

AbstractPurposeTo corroborate whether vessels on the surface of the optic nerve head can provide protection against the loss of underlying axons in subjects with manifest glaucoma.MethodsIn this pilot study, thirty-six glaucomatous eyes with a perimetric defect in the Bjerrum area were included. The retinal nerve fiber layer (RNFL) thickness was measured in each of the sectors of the clock-hour map obtained by Cirrus HD-OCT considering the presence or absence of blood vessels. These sectors were related with their corresponding areas of the retina examined in the visual field using a mathematical model of the retina introduced by Jansonius, in order to determine the values of threshold sensitivity in those areas in the presence or absence of vessels.ResultsWe corroborated the protective role of the blood vessel for peripapillary RNFL thickness of clock-hour 12 despite obtaining a p-value (p = 0.023; w = 228.5) close to the acceptance zone (p ≥ 0.05). The mean ± standard deviation with vessel and without vessel were 70.95 ± 24.35 and 88.46 ± 23.96, respectively. No differences were found between the mean values of threshold sensitivity to the presence or absence of blood vessels in each of the sectors considered.ConclusionsOur findings do not allow us to affirm that there is an association between the presence of a vessel and protection against glaucomatous damage in subjects with an advanced manifestation of the disease. In the future, more extensive studies are needed to study this relationship in subjects with early glaucoma.
Estimating occupancy dynamics and encounter rates with species misclassification: a semi-supervised individual-level approach
Authors: Spiers Anna I. , Royle J. Andrew , Torrens Christa L. , Joseph Maxwell B. 
Published: March 2021

AbstractLarge-scale, long-term biodiversity monitoring is essential to meeting conservation and land management goals and identifying threats to biodiversity. However, multispecies surveys are prone to various types of observation error, including false positive/negative detection, and misclassification, where a species is encountered but its species identity is not correctly identified. Previous methods assume an imperfect classifier produces species-level classifications, but in practice, particularly with human observers, we may end up with extraspecific classifications including “unknown”, morphospecies designations, and taxonomic identifications coarser than species. Disregarding these types of species misclassification in biodiversity monitoring datasets can bias estimates of ecologically important quantities such as demographic rates, occurrence, and species richness.Here we develop an occupancy model that accounts for species non-detection and misclassification. Our framework accommodates extinction and colonization dynamics, allows for additional uncertain ‘morphospecies’ designations in the imperfect species classifications, and makes use of individual specimen with known species identities in a semi-supervised setting. We compare the performance of our joint classification-occupancy model to a reduced classification model that discards information about occupancy and encounter rate on a withheld test set. We illustrate our model with an empirical case study of the carabid beetle (Carabidae) community at the National Ecological Observatory Network Niwot Ridge Mountain Research Station, west of Boulder, CO, USA, and quantify taxonomist identification error by accounting for classification probabilities.Species occupancy varied through time and across sites and species. The model yielded high probabilities (30 to 92% medians) of classification where the imperfect classifier matched the true species. The classification model informed by occupancy and encounter rates outperformed the classification that was not, and these differences were most pronounced for abundant species.Our probabilistic framework can be applied to datasets with imperfect species detection and classification. This model can identify commonly misclassified species, helping biodiversity monitoring organizations systematically prioritize which samples need validation by an expert. Our Bayesian approach propagates classification uncertainty to offer an alternative to making conservation decisions based on point estimates
Antibody elicited by HIV-1 immunogen vaccination in macaques displaces Env fusion peptide and destroys a neutralizing epitope
Authors: Abernathy Morgan E. , Gristick Harry B. , Vielmetter Jost , Keeffe Jennifer R. , Gnanapragasam Priyanthi NP , Lee Yu E. , Escolano Amelia , Gautam Rajeev , Seaman Michael S. , Martin Malcolm A. , Nussenzweig Michel C. , Bjorkman Pamela J. 
Published: March 2021

AbstractHIV-1 vaccine design aims to develop an immunogen that elicits broadly neutralizing antibodies against a desired epitope, while eliminating responses to off-target regions of HIV-1 Env. Here we report isolation and characterization of Ab1245, an off-target antibody against the Env gp120-gp41 interface, from V3-glycan patch immunogen-primed and boosted macaques. A 3.7Å cryo-EM structure of an Ab1245-Env complex reveals one Ab1245 Fab binding asymmetrically to Env trimer at the gp120-gp41 interface using its long CDRH3 to mimic regions of gp41. The mimicry includes positioning of a CDRH3 methionine into the gp41 tryptophan clasp, resulting in displacement of the fusion peptide and fusion peptide-proximal region. Despite fusion peptide displacement, Ab1245 is non-neutralizing even at high concentrations, implying that only two fusion peptides per trimer are required for viral–host membrane fusion. These structural analyses facilitate immunogen design to prevent elicitation of Ab1245-like antibodies that block neutralizing antibodies against the fusion peptide.
Dissecting the roles of MBD2 isoforms in regulating NuRD complex function during cellular differentiation
Authors: Schmolka Nina , Bhaskaran Jahnavi , Karemaker Ino D. , Baubec Tuncay 
Published: March 2021

AbstractThe Nucleosome Remodelling and Deacetylation (NuRD) complex is a crucial regulator of cellular differentiation. Two members of the Methyl-CpG-binding domain (MBD) protein family, MBD2 and MBD3, are known to be integral, but mutually exclusive subunits of the NuRD complex. Several MBD2 and MBD3 isoforms are present in mammalian cells, resulting in distinct MBD-NuRD complexes. If these different complexes serve distinct biochemical and/or functional activities during differentiation is not completely understood. Based on the essential role of MBD3 in lineage commitment, we systematically investigated a diverse set of MBD3 and MBD2 variants for their potential to rescue the differentiation block observed in mouse embryonic stem cells (ESCs) lacking MBD3. Our study reveals that while MBD3 is indeed crucial for ESC differentiation to neuronal cells, this function is independent of its MBD domain or binding to methylated DNA. While MBD3 isoforms are highly redundant, we identify that MBD2 isoforms vary in their potential to fully rescue the absence of MBD3 during lineage commitment. Full-length MBD2a only partially rescues the differentiation block; MBD2b, which lacks the N-terminal GR-rich repeat, fully rescues the differentiation block in MBD3 KO ES cells, and cells expressing the testis-specific isoform MBD2t that lacks the coiled-coil domain required for NuRD interactions are not able to generate any differentiated cells. In case of MBD2a, we further show that removing the m-CpG DNA binding capacity or the GR-rich repeat renders the protein fully redundant to MBD3, highlighting the requirements for these domains in diversifying NuRD complex function. In sum, our results highlight a partial redundancy of MBD2 and MBD3 during cellular differentiation and point to specific functions of distinct MBD2 isoforms and specific domains within the NuRD complex.
Implementation and acceleration of optimal control for systems biology
Authors: Sharp Jesse A , Burrage Kevin , Simpson Matthew J 
Published: March 2021

AbstractOptimal control theory provides insight into complex resource allocation decisions. The forward-backward sweep method (FBSM) is an iterative technique commonly implemented to solve two-point boundary value problems (TPBVPs) arising from the application of Pontryagin’s Maximum Principle (PMP) in optimal control. In this review we discuss the PMP approach to optimal control and the implementation of the FBSM. By conceptualising the FBSM as a fixed point iteration process, we leverage and adapt existing acceleration techniques to improve its rate of convergence. We show that convergence improvement is attainable without prohibitively costly tuning of the acceleration techniques. Further, we demonstrate that these methods can induce convergence where the underlying FBSM fails to converge. All code used in this work to implement the FBSM and acceleration techniques is available on GitHub athttps://github.com/Jesse-Sharp/Sharp2021.
A Phytosociological Classification of the Peruvian Vegetation
Authors: Galán-de-Mera Antonio , Campos-de-la-Cruz José , Linares-Perea Eliana , Montoya-Quino Juan , Torres-Marquina Iván , Vicente-Orellana José Alfredo 
Published: March 2021

AbstractThe present work is an update of the syntaxonomic scheme of Peru, with the results obtained to present. We currently recognize 218 phytosociological associations, of which 11 are novelties:Ageratino azangaroensis-Polylepidetum incarumass. nov.,Alchemillo pinnatae-Stipetum hans-meyeriass. nov.,Barnadesio dombeyanae-Polylepidetum racemosaeass. nov.,Eclipto prostratae-Echinochloetum crus-pavonisass. nov.,Geoffroeetum decorticantisass. nov.,Junellio arequipensis-Proustietum cuneifoliaeass. nov.,Lemnetum aequinoctialisass. nov.,Mutisio cochabambensis-Polylepidetum incarumass. nov.,Poo glaberrimae-Calamagrostietum eminentisass. nov.,Sarcocornietum andinaeass. nov., andSchino mollis-Prosopidetum calderensisass. nov. These 218 associations belong to 34 phytosociological classes, four of which are described here for the first time:Limoselletea australiscl. nov.,Mimulo glabrati-Plantaginetea australiscl. nov.,Tillandsietea latifolio-landbeckiicl. nov.,Woodsio montevidensis-Cheilanthetea pruinataecl. nov. In addition, 5 new orders (Alternanthero pungentis-Cynodontetalia dactylonisord. nov.,Coreopsietalia fasciculataeord. nov.,Echinopsio schoenii-Proustetalia cuneifoliaeord. nov.,Mimulo glabrati-Plantaginetalia australisord. nov.,Tillandsietalia latifolio-landbeckiiord. nov.), and 7 new alliances (Azollo filiculoidis-Lemnion gibbaeall. nov.,Ditricho submerse-Isoetion lechleriall. nov.,Echinopsio schoenii-Proustion cuneifoliaeall. nov.,Haageocerion acranthiall. nov.,Lepidio chichicarae-Cynodontion dactylonisall. nov.,Schoenoplection tatoraeall. nov., andTillandsion purpureo-latifoliaeall. nov.) are also described.
Prediction of burning performance and emissions indexes of a turboprop motor with artificial neural network
Authors: Kayaalp Kiyas , Metlek Sedat 
Published: March 2021

PurposeThe purpose of this paper is to estimate different air–fuel ratio motor shaft speed and fuel flow rates under the performance parameters depending on the indices of combustion efficiency and exhaust emission of the engine, a turboprop multilayer feed forward artificial neural network model. For this purpose, emissions data obtained experimentally from a T56-A-15 turboprop engine under various loads were used.Design/methodology/approachThe designed multilayer feed forward neural network models consist of two hidden layers. 75% of the experimental data used was allocated as training, 25% as test data and cross-referenced by the k-fold four value. Fuel flow, rotate per minute and air–fuel ratio data were used for the training of emission index input values on the designed models and EICO, EICO2, EINO2and EIUHCdata were used on the output. In the system trained for combustion efficiency, EICOand EIUHCdata were used at the input and fuel combustion efficiency data at the output.FindingsMean square error, normalized mean square error, absolute mean error functions were used to evaluate the error obtained from the system as a result of the test. As a result of modeling the system, absolute mean error values were 0.1473 for CO, 0.0442 for CO2, 0.0369 for UHC, 0.0028 for NO2, success for all exhaust emission data was 0.0266 and 7.6165e-10 for combustion efficiency, respectively.Originality/valueThis study has been added to the literature T56-A-15 turboprop engine for the current machine learning methods to multilayer feed forward neural network methods, exhaust emission and combustion efficiency index value calculation.