bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebrospinal Fluid and Plasma Procalcitonin for the Diagnosis of Neonatal Bacterial Meningitis
Authors: Dutta Sourabh , Sachdeva Naresh , Sanger Vilay , Pal Arnab , Ray Pallab 
Published: May 2021

AbstractObjectiveTo determine accuracy of cerebro-spinal fluid (CSF) procalcitonin (PCT) to diagnose neonatal bacterial meningitis (NBM) among septic neonates and compare with other index tests.DesignProspective, cross-sectional, single-gate studySettingLevel-3 neonatal unitPatientsNeonates with suspected sepsis undergoing lumbar punctureIndex testsCSF PCT, leukocyte count and biochemistry; plasma PCT and CSF:plasma PCT ratioReference standards“Definite meningitis” defined by positive CSF culture and/or gram stain and/or broad-based primer 16S rDNA polymerase chain reaction. “Definite or probable meningitis” defined by definite meningitis or probable meningitis (based on cytochemistry cut-offs).ResultsOf 216 eligible neonates, 18 had “definite meningitis” and 37 “definite or probable meningitis”. Median (Q1, Q3) CSF PCT level was higher in “definite meningitis” compared to “no definite meningitis” [0.429 (0.123, 1.300) vs. 0.181 (0.119, 0.286) ng/ml respectively, p=0.028]. Likewise, it was higher in “definite or probable meningitis” compared to no meningitis [0.245 (0.136, 0.675) vs. 0.170 (0.116, 0.28), p=0.01]. The area under ROC curve (AUC) of CSF PCT level for definite meningitis was 0.656 and for “definite or probable meningitis” 0.635. Paired comparisons of AUC of CSF PCT with other index tests were not significant. Based on a priori cut-off of 0.2 ng/ml, CSF PCT level had a sensitivity (95% CI) of 67% (50, 80), specificity 58% (54, 61), LR+ 1.6 (1.1, 2.0) and LR- 0.6 (0.3, 0.9).ConclusionsHigher values of CSF PCT are associated with NBM. CSF PCT cannot reliably discriminate between meningitis and no meningitis and is not superior to other CSF tests.
Lung Epithelial Cells Can Produce Antibodies Participating In Adaptive Humoral Immune Responses
Authors: Gao Erya , Shao Wenwei , Zhang Chi , Yu Meng , Dai Hui , Fan Tianrui , Zhu Zhu , Xu Weiyan , Huang Jing , Zhang Youhui , Qin Zhihai , Qiu Xiaoyan 
Published: May 2021

AbstractIt is generally believed that the main source of antibodies is B lymphocytes. In this study, our results first revealed that B cell-deficient mice could not produce antibodies specific for TI-Ags; however, mice with B cell deficiency could produce TD-Ag-specific antibodies, although antibody production was delayed compared with that in BALB/c mice after primary TD-Ag challenge. Subsequently, we identified that mouse lung epithelial cells could produce and secrete Ig, including IgM, IgA or IgG, which could display TD-Ag-specific antibody activity. Notably, the production of TD-Ag-specific antibodies by lung epithelial cells was found to be dependent on CD4+ T cells but not CD8+ T cells. Our findings indicate for the first time that B cells are not the only source of TD-Ag-specific antibodies but are essential for rapid TD-Ag-specific antibody production by non-B cells. This discovery may reveal a new mechanism for the production of specific antibodies.
Height, but not binding epitope, affects the potency of synthetic TCR agonists
Authors: Wilhelm Kiera B. , Morita Shumpei , McAffee Darren B. , Kim Sungi , O’Dair Mark K. , Groves Jay T. 
Published: May 2021

ABSTRACTUnder physiological conditions, peptide-MHC (pMHC) molecules can trigger T-cell receptors (TCRs) as monovalent ligands that are sparsely distributed on the plasma membrane of an antigen-presenting cell. TCR can also be activated by artificial clustering, such as with pMHC tetramers or antibodies; however, these strategies circumvent many of the natural ligand discrimination mechanisms of the T cell and can elicit non-physiological signaling activity. We have recently introduced a synthetic TCR agonist composed of an anti-TCRβ Fab’ antibody fragment covalently bound to a DNA oligonucleotide, which serves as a membrane anchor. This Fab’-DNA ligand efficiently activates TCR as a monomer when membrane-associated and exhibits a potency and activation profile resembling agonist pMHC. In this report, we explore the geometric requirements for effective TCR triggering and cellular activation by Fab’-DNA ligands. We find that T cells are insensitive to the ligand binding epitope on the TCR complex, but that length of the DNA tether is important. Increasing the intermembrane distance spanned by Fab’-DNA:TCR complexes decreases TCR triggering efficiency and T cell activation potency, consistent with the kinetic-segregation model of TCR triggering. These results establish design parameters for construction of synthetic TCR agonists that are able to activate polyclonal T cell populations, such as T cells from a human patient, in a similar manner as the native pMHC ligand.STATEMENT OF SIGNIFICANCEWe report geometric requirements for potent T cell activation by synthetic TCR ligands that mimic biophysical properties of the native pMHC ligand, but have the additional ability to activate polyclonal T cell populations. We find that increasing the space between apposed membranes at TCR binding events decreases ligand potency, but that changing the ligand’s binding epitope on the TCR has essentially no effect. The observed decrease in potency with increased ligand height is attributed to the longer ligands’ attenuated ability to trigger TCR at binding events.
High-Throughput Measurement and Machine Learning-Based Prediction of Collision Cross Sections for Drugs and Drug Metabolites
Authors: Ross Dylan H. , Seguin Ryan P. , Krinsky Allison M. , Xu Libin 
Published: May 2021

AbstractDrug metabolite identification is a bottleneck of drug metabolism studies. Ion mobility-mass spectrometry (IM-MS) enables the measurement of collision cross section (CCS), a unique physical property related to an ion’s gas-phase size and shape, which can be used to increase the confidence in the identification of unknowns. A current limitation to the application of IM-MS to the identification of drug metabolites is the lack of reference CCS values. In this work, we present the production of a large-scale database of drug and drug metabolite CCS values, assembled using high-throughputin vitrodrug metabolite generation and a rapid IM-MS analysis with automated data processing. Subsequently, we used this database to train a machine learning-based CCS prediction model, employing a combination of conventional 2D molecular descriptors and novel 3D descriptors. This novel prediction model enables the prediction of different CCS values for different protomers, conformers, and positional isomers for the first time.
Genes responsible for avoiding attack of a beetle, relating to the duration of death feigning
Authors: Tanaka Keisuke , Sasaki Ken , Matsumura Kentarou , Yajima Shunsuke , Miyatake Takahisa 
Published: May 2021

ABSTRACTPredator avoidance is an important behavior that affects the degree of adaptation of organisms. We compared the DNA variation of one of the predator-avoidance behaviors, the recently extensively studied “death-feigning behavior,” between the long strain bred for feigning death for a long time and the short strain bred for feigning death for a short time. To clarify how the difference in DNA sequences between the long and short strains corresponds to the physiological characteristics of the death-feigning duration at the transcriptome level, we performed comprehensive and comparative analyses of gene variants inTribolium castaneumstrains using DNA-re-sequence. The duration of death feigning involves many gene pathways, including caffeine metabolism, tyrosine metabolism, tryptophan metabolism, metabolism of xenobiotics by cytochrome P450, longevity regulating pathways, and circadian rhythm. Artificial selection based on the duration of death feigning results in the preservation of variants of genes in these pathways in the long strain. When an animal wake up from a near-death experience is closely related to its success in avoiding predation. This study suggests that many metabolic pathways and related genes may be involved in the decision-making process of anti-predator animal behavior by forming a network in addition to the tyrosine metabolic system, including dopamine, revealed in previous studies.
Distant water industrial fishing in developing countries: A case study of Madagascar
Authors: White Easton R. , Baker-Médard Merrill , Vakhitova Valeriia , Farquhar Samantha , Ramaharitra Tendro Tondrasoa 
Published: May 2021

AbstractAs industrial vessels continue to expand in both extractive capacity and spatial range, concerns have grown over foreign industrial fishing occurring within the marine territories of developing countries, both legally and illegally. Madagascar’s status as a “least developed country”, coupled with its high marine biodiversity, makes its waters particularly susceptible to fishing by distant water fishing nations (DWFNs). However, given constraints in management and research, it is unclear how foreign industrial fishing, both legal via foreign agreements and illegal, may impact local marine resources that many coastal communities depend on for food security, cultural meaning and livelihoods. We used satellite-derived fishing effort data from 2012-2020, via Global Fishing Watch, to analyze industrial fishing effort occurring within Madagascar’s Exclusive Economic Zone (EEZ). We documented 907,643 hours of industrial fishing within the Madagascar EEZ across 277 vessels from 17 different countries. We found that Taiwanease vessels (39.8%) using drifting longlines and Malagasy (17.2% shrimp trawlers were the most prevalent. Fishing effort was highly seasonal (68% of effort between October and February) and increased with higher global fish prices and the Indian Ocean Dipole, which is a measure of regional water temperature cycles. We also found a number of instances (17.6% of the fishing effort for 170,726 total hours) of foreign fishing vessels operating close to shore and within a number of marine protected areas. These results highlight the need for increased transparency surrounding foreign fishing agreements and unauthorized fishing within the waters of developing countries. Increases in industrial fishing effort and encroachment into near-shore areas has the potential to severely threaten current sustainable fisheries management initiatives by conservation organizations and coastal communities.HighlightsDistant water fishing nations dominated fishing efforts within Madagascar’s EEZ.Longlining by foreign nations was the dominant fishing mode and increased from October-February.Malagasy vessels focused on trawling for shrimp.Fishing effort increased during positive Indian Ocean Dipoles and with higher fish prices.Distant water fishing nations frequently fished close to shore and sometimes within MPAs.
Stable choice coding during changes of mind
Authors: Boyd-Meredith J Tyler , Piet Alex T , Dennis Emily Jane , Hady Ahmed El , Brody Carlos D 
Published: May 2021

AbstractHow do we choose the best action in a constantly-changing environment? Many natural decisions unfold in dynamic environments where newer observations carry better information about the present state of the world. Recent work has shown that rats can learn to optimally discount old evidence, updating their provisional decision when the environmental state changes. Provisional decisions are thought to be represented in the Frontal Orienting Fields (FOF), but this has only been tested in static environments where the provisional and final decisions are not easily dissociated. Here, we characterize the representation of accumulated evidence in rat FOF during decision-making in a dynamic environment. We find that FOF encodes evidence throughout decision formation with a temporal gain modulation that rises until the period when the animal may need to act. Using a behavioral model to predict the timing of changes of mind revealed that FOF neurons respond rapidly to these events, representing the new provisional decisions in their firing rates. Our results suggest that the FOF represents provisional decisions even in dynamic, uncertain environments, allowing for rapid motor execution when it is time to act.
Photoperiodic Flowering Response of Essential Oil, Grain, and Fiber Hemp (Cannabis sativaL.) Cultivars
Authors: Zhang Mengzi , Anderson Steven L. , Brym Zachary , Pearson Brian J. 
Published: May 2021

AbstractCultivation of hemp (Cannabis sativaL.) in tropical and subtropical regions can be challenging if flowering behavior of a given cultivar is unknown, poorly understood, or not accurately selected for the photoperiod. Identifying cultivars adapted to local environmental conditions is key to optimizing hemp vegetative and flowering performance. We investigated the effects of varying light cycles in regulating extension growth and flowering response of 15 essential oil and 12 fiber/grain hemp cultivars both in indoors and outdoors. Plants were subjected to eleven photoperiods in the controlled rooms ranging from 12 h to 18 h, and natural day length in the field. The critical photoperiod threshold was identified for seven essential oil cultivars and two fiber/grain cultivars. ‘Cherry Wine-CC’, ‘PUMA-3’, and ‘PUMA-4’ had the shortest critical day length between 13 h 45 min and 14 h. The flowering of essential oil cultivars was generally delayed by 1 to 2 d when photoperiod exceeded 13 h compared to 12 h, and flowering was further delayed by 7 to 8 d when photoperiod exceed 14 h. In fiber/grain cultivars, flowering was generally delayed by 1 to 3 d when day length exceeded 14 h. Flowering for most essential oil cultivars was delayed by 5 to 13 d under 14 h photoperiod compared to 13 h 45 min, suggesting a photoperiod difference as little as 15 min can significantly influence the floral initiation of some essential oil cultivars. Cultivars represented by the same name but acquired from different sources can perform differently under the same environmental conditions, suggesting genetic variation among cultivars with the same name. Average days to flower of fiber/grain cultivars was correlated with reported cultivar origin with faster flowering occurring among northern cultivars when compared to southern cultivars. Plant height generally increased as the day length increased in essential oil cultivars but was not affected in fiber/grain cultivars. In addition, civil twilight of approximately 2 µmol·m-2·s-1was discovered to be biologically effective in regulating hemp flowering. Collectively, we conclude that most of the essential oil cultivars and some southern fiber/grain cultivars tested express suitable photoperiods for tropical and sub-tropical region cultivation.
The FDA-approved drug apremilast suppresses alcohol intake: clinical and pre-clinical validation
Authors: Grigsby Kolter B. , Mangieri Regina A. , Roberts Amanda J. , Lopez Marcelo F. , Tran Alexander , Firsick Evan J. , Townsley Kayla G. , Beneze Alan , Bess Jessica , Eisenstein Toby K. , Meissler Joseph J. , Light John M. , Miller Jenny , Quello Susan , Shadan Farhad , Skinner Michael , Aziz Heather C. , Metten Pamela , Morissett Richard A. , Crabbe John C. , Roberto Marisa , Becker Howard C. , Mason Barbara J. , Ozburn Angela R. 
Published: May 2021

AbstractTreatment options for Alcohol Use Disorders (AUD) have minimally advanced since 2004, while the annual deaths and economic toll have become alarmingly high. Bringing potential therapeutics beyond the bench and into the clinic for AUD requires rigorous pharmacological screening across molecular, behavioral, pre-clinical, and clinical studies in neuroscience. The repurposing of FDA-approved compounds is an effective and expedited means of screening pharmacotherapies for AUD. Here, we demonstrate that apremilast, a phosphodiesterase type 4 inhibitor that is FDA approved for psoriasis and psoriatic arthritis, reduces binge-like alcohol intake and behavioral measures of motivation in unique, preclinical genetic risk models for drinking to intoxication and reduces excessive alcohol drinking in models of stress-facilitated drinking and alcohol dependence. In a double blind, placebo-controlled human laboratory study in non-treatment seeking individuals with AUD, apremilast significantly reduced the number of drinks per day. Lastly, using site-directed drug infusions and electrophysiology we determined that apremilast may act by increasing neural activity in the nucleus accumbens, an important alcohol-related brain region, to reduce alcohol intake in mice. These results demonstrate that apremilast reduces excessive alcohol drinking across a spectrum of AUD severity and support its importance as a potential therapeutic for AUD.
Novel Object Detection and Multiplexed Motion Representation in Retinal Bipolar Cells
Authors: Gaynes John A. , Budoff Samuel A. , Grybko Michael J. , Hunt Joshua B. , Poleg-Polsky Alon 
Published: May 2021

AbstractAntagonistic interactions between the center and surround receptive field (RF) components lie at the heart of the computations performed in the visual system. Center-surround RFs are thought to enhance responses to spatial contrasts (i.e., edges), but how they contribute to motion processing is unknown. Here, we addressed this question in retinal bipolar cells, the first visual neuron with classic center-surround interactions. We found that bipolar glutamate release emphasizes objects that emerge in the RF; their responses to continuous motion are smaller, slower, and cannot be predicted by signals elicited by stationary stimuli. The alteration in signal dynamics induced by novel objects dwarfs the enhancement of spatial edges and can be explained by priming of RF surround during continuous motion. These findings echo the salience of human visual perception and demonstrate an unappreciated capacity of the center-surround architecture to facilitate novel object detection and multiplexed encoding of distinct sensory modalities.
Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes
Authors: Gaudreau Marie-Claude , Gudi Radhika R. , Li Gongbo , Johnson Benjamin M. , Vasu Chenthamarakshan 
Published: May 2021

AbstractProgressive destruction of pancreatic islet β-cells by immune cells is a primary feature of type 1 diabetes (T1D) and therapies that can restore the functional β-cell mass are needed to alleviate disease progression. Here, we report the use of mesenchymal stromal/stem cells (MSCs) for the production and delivery of Gastrin, a peptide-hormone which is produced by intestinal cells and fetal islets and can increase β-Cell mass, to promote protection from T1D. A single injection of syngeneic MSCs that were engineered to express Gastrin (Gastrin-MSCs) caused a significant delay in hyperglycemia in non-obese diabetic (NOD) mice compared to engineered control-MSCs. Similar treatment of early-hyperglycemic mice caused the restoration of euglycemia for a considerable duration, and these therapeutic effects were associated with protection of, and/or higher frequencies of, insulin producing islets and less severe insulitis. While the overall immune cell phenotype was not affected profoundly upon treatment using Gastrin-MSCs or upon in vitro culture, pancreatic lymph node cells from Gastrin-MSC treated mice, upon ex vivo challenge with self-antigen, showed a Th2 and Th17 bias, and diminished the diabetogenic property in NOD-Rag1deficient mice suggesting a disease protective immune modulation under Gastrin-MSC treatment associated protection from hyperglycemia. Overall, this study shows the potential of production and delivery of Gastrin in vivo, by MSCs, in protecting insulin producing β-cells and ameliorating the disease progression in T1D.
Insularity forcing on plant persistence strategies in edaphic island systems
Authors: Conti Luisa , Méndez-Castro Francisco E. , Chytrý Milan , Götzenberger Lars , Hájek Michal , Horsák Michal , Jiménez-Alfaro Borja , Klimešová Jitka , Zelený David , Ottaviani Gianluigi 
Published: May 2021

AbstractAimTrait-based approaches are increasingly implemented in island biogeography, providing key insights into the eco-evolutionary dynamics of insular systems. However, what determines persistence of plant species once they have arrived and established in an island remains largely unexplored. Here, we examined links between non-acquisitive persistence strategies and insularity across three terrestrial edaphic island systems, hypothesising that insularity promotes strategies for local persistence.LocationEurope: Western Carpathians, Moravia, and Cantabrian Range.Time periodPresent.Major taxa studiedVascular plants.MethodsFor each system, we used linear models at the island scale to test whether persistence-related plant trait patterns (average trait values and diversity) depend on three insularity metrics (island size, isolation and target effect). We focused on patterns of edaphic island specialists because, in contrast to matrix-derived species, their presence is confined to the edaphic islands.ResultsWe found that insularity metrics explained large proportions in the variation of the average and diversity of persistence-related traits of edaphic island specialists. Insularity was associated with a decline in the proportion of island specialists that have clonal abilities, yet it affected trait values of specialists towards enhanced abilities to persist locally (e.g. more extensive lateral spread) while reducing trait variability. Higher degrees of insularity within the systems were translated to stronger effects on functional trait patterns.Main conclusionsInsularity affects plant species diversity, distribution and forms in terrestrial island-like systems, similarly as it is assumed for true islands. Insularity – measured using a single (island size, isolation) or combined (target effect) predictors – may operate selecting for enhanced and less diverse persistence strategies. Ultimately, this process, which we call insularity forcing, operates as a selective process to promote species ability to avoid local extinction and to persist on terrestrial islands.