bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regular aerobic exercise is positively associated with hippocampal structure and function in young and middle-aged adults
Authors: Hendrikse Joshua , Chye Yann , Thompson Sarah , Rogasch Nigel C. , Suo Chao , Coxon James , Yücel Murat 
Published: August 2020

AbstractRegular exercise has numerous benefits for brain health, including the structure and function of the hippocampus. The hippocampus plays a critical role in memory function, and is altered in a number of psychiatric disorders associated with memory impairments (e.g. depression and schizophrenia), as well as healthy ageing. While many studies have focussed on how regular exercise may improve hippocampal integrity in older individuals, less is known about these effects in young to middle-aged adults. Therefore, we assessed the associations of regular exercise and cardiorespiratory fitness with hippocampal structure and function in these age groups. We recruited 40 healthy young to middle-aged adults, comprised of two groups (n = 20) who self-reported either high or low levels of exercise, according to World Health Organisation guidelines. We assessed cardiorespiratory fitness using a graded exercise test (VO2max) and hippocampal structure via manual tracing of T1-weighted magnetic resonance images. We also assessed hippocampal function using magnetic resonance spectroscopy to derive estimates of NAA concentration and hippocampal-dependent associative memory and pattern separation tasks. We observed evidence of increased N-acetyl-aspartate concentration and associative memory performance in individuals engaging in high levels of exercise. However, no differences in hippocampal volume or pattern separation capacity were observed between groups. Cardiorespiratory fitness was positively associated with hippocampal volume (left, right, and bilateral), N-acetyl-aspartate concentration, and pattern separation. However, no association was observed between cardiorespiratory fitness and associative memory. Therefore, we provide evidence that higher levels of exercise and cardiorespiratory fitness are associated with improved hippocampal structure and function. Exercise may provide a low-risk, effective method of improving hippocampal integrity in an early-to-mid-life stage.
Non-epigenetic mechanisms enable short memories of the environment for cell cycle commitment
Authors: Qu Yimiao , Jiang Jun , Liu Xiang , Yang Xiaojing , Tang Chao 
Published: August 2020

ABSTRACTCells continuously survey their environment in order to make fundamental decisions, including whether to divide, migrate, or differentiate. However, a fascinating phenomenon in biology is that cells often possess memory—they temporally integrate both past and present signals to make a reliable decision. Cellular memory manifests across different biological systems over different timescales, and a variety of underlying molecular mechanisms have been proposed. Here we investigate a non-epigenetic molecular mechanism underpinning how a single yeast cell can remember its recent environmental history to decide whether to enter the cell cycle. This “memories” is encoded by the phosphorylation level of the cell cycle inhibitor Whi5. G1 cyclin Cln3 senses environmental nutrient levels and promotes cell-cycle entry by phosphorylating and thus inactivating Whi5. We developed an optogenetic system whereby the nuclear localization of Cln3 can be rapidly and reversibly controlled by light. By monitoring cellular response to different temporal profiles of Cln3, we found that cell cycle entry requires the time duration of nuclear Cln3, supporting the model of “cellular memories”. Moreover, instead of the memory could last for the entire G1 phase as previously observed in glucose, we found Whi5 re-activates rapidly, with a similar half-time ∼ 12 min, in a variety of nutrient and stress conditions. Our results suggest yeast cell can shortly remember its recent environmental cues to decide whether to enter the cell cycle.
The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis
Authors: Démoulins Thomas , Brügger Melanie , Zumkehr Beatrice , Oliveira Esteves Blandina I. , Mehinagic Kemal , Fahmi Amal , Borcard Loïc , Taddeo Adriano , Posthaus Horst , Benarafa Charaf , Ruggli Nicolas , Alves Marco P. 
Published: August 2020

ABSTRACTThe human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the specific features of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a state-of-the-art model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4 and CD8 T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 responseper se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity.AUTHOR SUMMARYBy using a state-of-the-art translational model with full accessibility to the small airways at defined early life periods, we provide an unpreceded characterization of the developing T cell compartment in the distal lungs of healthy and RSV-infected neonates. This process is highly dynamic and tightly regulated, characterized by colonizing T-cell subsets that synergize towards a narrow pro-tolerogenic immunological window. We believe our work constitutes a solid basis to clarify the age dependency of RSV immunopathogenesis, and should be considered in vaccine design, which remains challenging after five decades of effort.
Sub-lethal pyrethroid exposure and ageing lead to pronounced changes in gene expression in insecticide resistanceAnopheles coluzzii
Authors: Ingham V A , Brown F , Ranson H 
Published: August 2020

AbstractBackgroundMalaria control is heavily reliant on the use of insecticides that target and kill the adult female Anopheline vector. The intensive use of insecticides of the pyrethroid class has led to widespread resistance in mosquito populations. The intensity of pyrethroid resistance in some settings in Africa means mosquitoes can contact bednets treated with this insecticide class multiple times with minimal mortality effects. However, the sublethal exposure may affect other traits controlling the vectorial capacity or fitness of the mosquito.ResultsHere we show that sublethal exposure of a highly resistantAnopheles coluzziipopulation originally from Burkina Faso to the pyrethroid deltamethrin results in large and sustained changes to transcript expression. We identify five clear patterns in the data showing changes to transcripts relating to: DNA repair, respiration, translation, ion transport and oxioreductase processes. Further, we highlight differential regulation of transcripts from detoxification families previously linked with insecticide resistance, in addition to clear down-regulation of the oxidative phosphorylation pathway both indicative of changes in metabolism post-exposure. Finally, we show that both ageing and diel cycle have major effects on known insecticide resistance related transcripts.ConclusionSub-lethal pyrethroid exposure, ageing and the diel cycle results in large-scale changes in the transcriptome of the major malaria vectorAnopheles coluzzii. Our data strongly supports further phenotypic studies on how transcriptional changes such as reduced expression of the oxidative phosphorylation pathway or pyrethroid induced changes to redox state might impact key mosquito traits, such as vectorial capacity and life history traits.
DeCompress: tissue compartment deconvolution of targeted mRNA expression panels using compressed sensing
Authors: Bhattacharya Arjun , Hamilton Alina M. , Troester Melissa A. , Love Michael I. 
Published: August 2020

ABSTRACTTargeted mRNA expression panels, measuring up to 800 genes, are used in academic and clinical settings due to low cost and high sensitivity for archived samples. Most samples assayed on targeted panels originate from bulk tissue comprised of many cell types, and cell-type heterogeneity confounds biological signals. Reference-free methods are used when cell-type-specific expression references are unavailable, but limited feature spaces render implementation challenging in targeted panels. Here, we presentDeCompress, a semi-reference-free deconvolution method for targeted panels.DeCompressleverages a reference RNA-seq or microarray dataset from similar tissue to expand the feature space of targeted panels using compressed sensing. Ensemble reference-free deconvolution is performed on this artificially expanded dataset to estimate cell-type proportions and gene signatures. In simulated mixtures, four public cell line mixtures, and a targeted panel (1199 samples; 406 genes) from the Carolina Breast Cancer Study,DeCompressrecapitulates cell-type proportions with less error than reference-free methods and finds biologically relevant compartments. We integrate compartment estimates intocis-eQTL mapping in breast cancer, identifying a tumor-specificcis-eQTL forCCR3(C-C Motif Chemokine Receptor 3) at a risk locus.DeCompressimproves upon reference-free methods without requiring expression profiles from pure cell populations, with applications in genomic analyses and clinical settings.
SARS-CoV-2 Infection And Longitudinal Fecal Screening In Malayan Tigers (Panthera tigris jacksoni), Amur Tigers (Panthera tigris altaica), And African Lions (Panthera leo krugeri) At The Bronx Zoo, New York, USA
Authors: Bartlett Susan L. , Diel Diego G. , Wang Leyi , Zec Stephanie , Laverack Melissa , Martins Mathias , Caserta Leonardo Cardia , Killian Mary Lea , Terio Karen , Olmstead Colleen , Delaney Martha A. , Stokol Tracy , Ivančić Marina , Jenkins-Moore Melinda , Ingerman Karen , Teegan Taryn , McCann Colleen , Thomas Patrick , McAloose Denise , Sykes John M. , Calle Paul P. 
Published: August 2020

AbstractSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) emerged as the cause of a global pandemic in 2019-2020. In March 2020 New York City became the USA epicenter for the pandemic. On March 27, 2020 a Malayan tiger (Panthera tigris jacksoni) at the Bronx Zoo in New York City developed a cough and wheezing with subsequent inappetence. Over the next week, an additional Malayan tiger and two Amur tigers (P. t. altaica) in the same building and three lions (Panthera leo krugeri) in a separate building also became ill. The index case was immobilized, and physical examination and bloodwork results were unremarkable. Thoracic radiography and ultrasonography revealed peribronchial cuffing with bronchiectasis, and mild lung consolidation with alveolar-interstitial syndrome, respectively. SARS-CoV-2 RNA was identified by real-time, reverse transcriptase PCR (rRT-PCR) on oropharyngeal and nasal swabs and tracheal wash fluid. Cytologic examination of tracheal wash fluid revealed necrosis, and viral RNA was detected in necrotic cells by in situ hybridization, confirming virus-associated tissue damage. SARS-CoV-2 was isolated from the tracheal wash fluid of the index case, as well as the feces from one Amur tiger and one lion. Fecal viral RNA shedding was confirmed in all seven clinical cases and an asymptomatic Amur tiger. Respiratory signs abated within 1-5 days for most animals, though persisted intermittently for 16 days in the index case. Fecal RNA shedding persisted for as long as 35 days beyond cessation of respiratory signs. This case series describes the clinical presentation, diagnostic evaluation, and management of tigers and lions infected with SARS-CoV-2, and describes the duration of viral RNA fecal shedding in these cases. This report documents the first known natural transmission of SARS-CoV-2 from humans to animals in the USA, and is the first report of SARS-CoV-2 in non-domestic felids.
Phosphorylation of Serine114 of the transcription factor ABSCISIC ACID INSENSITIVE 4 is essential for activity
Authors: Eisner Nadav , Maymon Tzofia , Sanchez Ester Cancho , Bar-Zvi Dana , Brodsky Sagie , Finkelstein Ruth , Bar-Zvi Dudy 
Published: August 2020

AbstractThe transcription factor ABA-INSENSITIVE(ABI)4 has diverse roles in regulating plant growth, including inhibiting germination and reserve mobilization in response to ABA and high salinity, inhibiting seedling growth in response to high sugars, inhibiting lateral root growth, and repressing light-induced gene expression. ABI4 activity is regulated at multiple levels, including gene expression, protein stability, and activation by phosphorylation. Although ABI4 can be phosphorylated at multiple residues by MAPKs, we found that S114 is the preferred site of MPK3. To examine the possible biological role of S114 phosphorylation, we transformedabi4-1mutant plants withABI4pro::ABI4constructs encoding wild type (114S), phosphorylation-null (S114A) or phosphomimetic (S114E) forms of ABI4. Phosphorylation of S114 is necessary for the response to ABA, glucose, salt stress, and lateral root development, where theabi4phenotype could be complemented by expressing ABI4(114S) or ABI4(S114E) but not ABI4(S114A). Comparison of root transcriptomes in ABA-treated roots ofabi4-1mutant plants transformed with constructs encoding the different phosphorylation-forms of S114 of ABI4 revealed that 85% of the ABI4-regulated genes whose expression pattern could be restored by expressing ABI4(114S) are down-regulated by ABI4. Over half of the ABI4-modulated genes were independent of the phosphorylation state of ABI4; these are enriched for stress responses. Phosphorylation of S114 was required for regulation of 35% of repressed genes, but only 17% of induced genes. The genes whose repression requires the phosphorylation of S114 are mainly involved in embryo and seedling development, growth and differentiation, and regulation of gene expression.HighlightsTranscription factor ABI4 is a substrate of MAP kinases.MPK3 preferentially phosphorylates Serine 114 of ABI4.Phosphorylated Serine 114 of ABI4 is required for the complementation of abi4 mutants.Phosphorylated ABI4 acts primarily as a repressor.
A novel compound that disrupts mitotic spindle poles in human cells
Authors: Jaunky Dilan , Husser Mathieu , Larocque Kevin , Liu Peter , Thampipillai Sajinth , Forgione Pat , Piekny Alisa 
Published: August 2020

ABSTRACTWe characterize the mechanism of action of a new microtubule-targeting compound in cells. Microtubule-targeting drugs are used as successful anti-cancer therapies. We synthesized a family of compounds that share a common scaffold and have several functional groups amenable to modifications. We found that one of the active derivatives, C75, reduces cell viability and prevents microtubule polymerizationin vitro. In this study, we explore the phenotypes caused by C75 in cells. It causes mitotic arrest and spindle phenotypes in several cancer cell lines in the nanomolar range. C75 can bind to the Colchicine-pocket on tubulinin vitro, but causes different effects on microtubules in cells. While Colchicine causes a decrease in microtubules and spindle pole collapse without re-growth, similar concentrations of C75 cause a rapid loss of microtubules and spindle pole fragmentation followed by microtubule re-growth to form multipolar spindles. In addition, C75 and Colchicine synergize for reduced viability and spindle phenotypes. Importantly, the phenotypes caused by C75 are similar to those caused by the depletion of ch-TOG, a microtubule polymerase, and tubulin and ch-TOG are displaced and oscillate in C75-treated cells. This suggests that C75 causes microtubule depolymerization in cells either directly or indirectly via inhibiting ch-TOG. This unique effect of C75 on microtubules warrants further exploration of its anti-cancer potential.
3D Bioprinting of Graphene Oxide-Incorporated Cell-laden Bone Mimicking Scaffolds for Promoting Scaffold Fidelity, Osteogenic Differentiation and Mineralization
Authors: Zhang Jianhua , Eyisoylu Hande , Qin Xiao-Hua , Rubert Marina , Müller Ralph 
Published: August 2020

AbstractBioprinting is a promising technique for facilitating the fabrication of engineered bone tissues for patient-specific defect repair and for developingin vitrotissue/organ models forex vivotests. However, polymer-based ink materials often result in insufficient mechanical strength, low scaffold fidelity and loss of osteogenesis induction because of the intrinsic swelling/shrinking and bioinert properties of most polymeric hydrogels. In this work, we developed a novel human mesenchymal stem cell (hMSC)-laden graphene oxide (GO)/alginate/gelatin composite bioink to form 3D bone mimicking scaffolds. Our results showed that the GO composite bioinks with higher GO concentrations improved the bioprintability, scaffold fidelity, compressive modulus and cell viability. The higher GO concentration increased the cell body size and DNA content. The 1GO group had the highest osteogenic differentiation of hMSC with the upregulation of osteogenic-related gene expression at day 42. To mimic critical-sized calvarial bone defects in mice, 3D cell-laden GO defect scaffolds with complex geometries were successfully bioprinted. 1GO maintained the best scaffold fidelity and had the highest mineral volume after culturing in the bioreactor for 42 days. Finally, the 1GO bioink has been demonstrated great potential for 3D bioprinting in applications of bone model and bone tissue engineering.
Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of Synaptotagmin-1
Authors: Huson Vincent , Meijer Marieke , Dekker Rien , ter Veer Mirelle , Ruiter Marvin , van Weering Jan , Verhage Matthijs , Cornelisse L. Niels 
Published: August 2020

AbstractPreviously, we showed that modulation of the energy barrier for synaptic vesicle fusion boosts release rates supralinearly (Schotten, 2015). Here we show that mouse hippocampal synapses employ this principle to trigger Ca2+-dependent vesicle release and post-tetanic potentiation (PTP). We assess energy barrier changes by fitting release kinetics in response to hypertonic sucrose. Mimicking activation of the C2A domain of the Ca2+-sensor Synaptotagmin-1 (Syt1), by adding a positive charge (Syt1D232N) or increasing its hydrophobicity (Syt14W), lowers the energy barrier. Removing Syt1 or impairing its release inhibitory function (Syt19Pro) increases spontaneous release without affecting the fusion barrier. Both phorbol esters and tetanic stimulation potentiate synaptic strength, and lower the energy barrier equally well in the presence and absence of Syt1. We propose a model where tetanic stimulation activates Syt1 dependent and independent mechanisms that lower the energy barrier independently in an additive manner to produce PTP by multiplication of release rates.
Molecular crowding in single eukaryotic cells: using cell environment biosensing and single-molecule optical microscopy to probe dependence on extracellular ionic strength, local glucose conditions, and sensor copy number
Authors: Shepherd Jack W , Lecinski Sarah , Wragg Jasmine , Shashkova Sviatlana , MacDonald Chris , Leake Mark C 
Published: August 2020

AbstractThe physical and chemical environment inside cells is of fundamental importance to all life but has traditionally been difficult to determine on a subcellular basis. Here we combine cutting-edge genomically integrated FRET biosensing to readout localized molecular crowding in single live yeast cells. Confocal microscopy allows us to build subcellular crowding heatmaps using ratiometric FRET, while whole-cell analysis demonstrates crowding is reduced when yeast is grown in elevated glucose concentrations. Simulations indicate that the cell membrane is largely inaccessible to these sensors and that cytosolic crowding is broadly uniform across each cell over a timescale of seconds. Millisecond single-molecule optical microscopy was used to track molecules and obtain brightness estimates that enabled calculation of crowding sensor copy numbers. The quantification of diffusing molecule trajectories paves the way for correlating subcellular processes and the physicochemical environment of cells under stress.
ELAV proteins bind and stabilize C/EBP mRNA in the induction of long-term memory in Aplysia
Authors: Mirisis Anastasios A. , Kopec Ashley M. , Carew Thomas J. 
Published: August 2020

AbstractLong-term memory (LTM) formation is a critical survival process by which an animal retains information about prior experiences in order to guide future behavior. In the experimentally advantageous marine mollusk Aplysia, LTM for sensitization can be induced by the presentation of two aversive shocks to the animal’s tail. Each of these training trials recruits distinct growth factor signaling systems that promote LTM formation. Specifically, whereas intact TrkB signaling during Trial 1 promotes an initial and transient increase of the immediate early gene apc/ebp mRNA, a prolonged increase in apc/ebp gene expression required for LTM formation requires the addition of TGFβ signaling during Trial 2. Here we explored the molecular mechanisms by which Trial 2 achieves the essential prolonged gene expression of apc/ebp. We find that this prolonged gene expression is not dependent on de novo transcription, but that apc/ebp mRNA synthesized by Trial 1 is post-transcriptionally stabilized by interacting with the RNA-binding protein ApELAV. This interaction is promoted by p38 MAPK activation initiated by TGFβ. We further demonstrate that blocking the interaction of ApELAV with its target mRNA during Trial 2 blocks both the prolonged increase in apc/ebp gene expression and the behavioral induction of LTM. Collectively, our findings elucidate both when and how ELAV proteins are recruited for the stabilization of mRNA in LTM formation.Significance StatementIn the present paper we significantly extend the general field of molecular processing in LTM by describing a novel form of pre-translational processing required for LTM which relies on the stabilization of a newly synthesized mRNA by a unique class of RNA binding proteins (ELAVs). In the broad field of molecular mechanisms of transcription-dependent LTM, there are now compelling data showing that important processing can occur after transcription of a gene, but before translation of the message into protein. Although the potential importance of ELAV proteins in LTM formation has previously been reported, to date there has been no mechanistic insight into the specific actions of ELAV proteins in stabilization of mRNAs known to be critical for LTM. Our new findings thus complement and extend this literature by demonstrating when and how this post-transcriptional gene regulation is mediated in the induction of LTM.