bluuebunny/crossref_metadata_2025_split huggingface dataset:
Episodic memory encoding by a place cell sub-population
Authors: Ormond Jake , Serka Simon A. , Johansen Joshua P. 
Published: June 2019

ABSTRACTStudy of the hippocampal place cell system has greatly enhanced our understanding of memory encoding for distinct places, but how episodic memories for distinct experiences occurring within familiar environments are encoded is not clear. One possibility is that different place cell populations encode details of the novel experience or maintain the representation of the unchanged environment. We developed an aversive spatial decision making task which induced partial remapping in CA1, allowing us to identify both remapping and stable cell populations. We found that remapping cells exhibited distinct features not present in stable cells. During memory encoding, their theta phase preferences shifted to earlier phases, when CA3 inputs are strongest. Further, their recruitment into replay events increased during learning, unlike that of stable cells. Our demonstration of a sub-population of place cells identified on the basis of their degree of remapping and exhibiting unique changes in their spike firing properties with learning lend support to a model in which novel and familiar spatial/contextual information is encoded and maintained, respectively, by separate place cell populations.
Integrative analysis of proteome and transcriptome dynamics duringBacillus subtilisspore revival
Authors: Swarge Bhagyashree , Jonker Martijs , Abhyankar Wishwas , Hoefsloot Huub , de Koster Chris G. , Brul Stanley , de Koning Leo J. 
Published: June 2019

AbstractBacillus subtilisforms highly resistant, metabolically inactive dormant spores upon nutrient limitation. These endospores pose challenges to the food and medical sectors. Spores reactivate their metabolism upon contact with germinants and develop into vegetative cells. The activation of the molecular machinery that triggers the progress of germination and spore outgrowth is still unsettled. To gain further insight in spore germination and outgrowth processes, the transcriptome and proteome changeover during spore germination and outgrowth to vegetative cells, was analysed.B. subtilistranscriptome analysis allow us to trace the different functional groups of genes expressed. For each time-point sample, the change in the spore proteome was quantitatively monitored relative to the reference proteome of15N metabolically labelled vegetative cells. We observed until the phase transition, i.e. completion of germination, no significant change in the proteome. We have identified 36 transcripts present abundantly in the dormant spores. This number is in close agreement with the previous findings. These transcripts mainly belong to the genes encoding small acid soluble proteins (sspE, sspO, sspI, sspK, sspF) and proteins with uncharacterized functions. We observed in total 3152 differentially expressed genes, but ‘only’ 323 differentially expressed proteins (total 451 proteins identified and quantified). Our data shows that 173 proteins from dormant spores, both spore unique proteins and protein shared with vegetative cells, are lost during the phase transitioning period. This loss is in addition to the active protein degradation, undertaken by the spore proteases such as Gpr, as germination and outgrowth proceeds. Further analysis is required to functionally interpret the observed protein loss. The observed diverse timing of the synthesis of different protein sets reveals a putative core-strategy of the revival of ‘life’ starting from theB. subtilisspore.
Neonatal genetics of gene expression reveal the origins of autoimmune and allergic disease risk
Authors: Huang Qin Qin , Tang Howard H. F. , Teo Shu Mei , Ritchie Scott C. , Nath Artika P. , Brozynska Marta , Salim Agus , Bakshi Andrew , Holt Barbara J. , Mok Danny , Khor Chiea Chuen , Sly Peter D. , Holt Patrick G. , Holt Kathryn E. , Inouye Michael 
Published: June 2019

AbstractChronic immune-mediated diseases of adulthood often originate in early childhood. To investigate genetic associations between neonatal immunity and disease, we collected cord blood samples from a birth cohort and mapped expression quantitative trait loci (eQTLs) in resting monocytes and CD4+ T cells as well as in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) stimulation, respectively. Cis-eQTLs were largely specific to cell type or stimulation, and response eQTLs were identified for 31% of genes with cis-eQTLs (eGenes) in monocytes and 52% of eGenes in CD4+ T cells. We identified trans-eQTLs and mapped cis regulatory factors which act as mediators of trans effects. There was extensive colocalisation of causal variants for cell type- and stimulation-specific neonatal cis-eQTLs and those of autoimmune and allergic diseases, in particular CTSH (Cathepsin H) which showed widespread colocalisation across diseases. Mendelian randomisation showed causal neonatal gene transcription effects on disease risk for BTN3A2, HLA-C and many other genes. Our study elucidates the genetics of gene expression in neonatal conditions and cell types as well as the aetiological origins of autoimmune and allergic diseases.
The effects of losing sex on the molecular evolution of plant defense
Authors: Carmona Diego , Hollister Jesse D. , Greiner Stephan , Wright Stephen I. , Ness Rob W. , Johnson Marc T.J. 
Published: June 2019

AbstractIt is hypothesized that the loss of sexual reproduction and reduced recombination rates decrease the ability for hosts to evolve in response to selection by parasites. Using transcriptomes from 32 species, we test whether repeated losses of sex in the plant genusOenotherahas resulted in changes to the evolution of defense genes against herbivores and pathogens. To achieve this, the function of 2,431Oenotheraorthologous genes was determined based on GO annotations fromArabidopsis thaliana. Phylogenetic Analysis by Maximum Likelihood (PAML) was then used to examine how the patterns of molecular evolution in 721 defense and 1,710 non-defense genes differ between sexual (16 spp.) and asexual (16 spp.) taxa. We test whether the relative rates of nonsynonymous to synonymous substitutions (ω = dN/dS) in proteins with defensive function were higher in lineages with sexual reproduction (ωsexual> ωa-sexual), and we asked if such patterns were exclusive for defense genes or not. We detected variability in the rate of amino acid replacements of proteins in >50% of genes and positive selection on 3% of the genes examined. Nevertheless, our results clearly show that on average, signatures of positive and purifying selection on defense and non-defense genes are similar and only a small number of specific genes related to plant immune function may be affected by a loss of sex.
Chemogenetic Control of Nanobodies
Authors: Farrants Helen , Tarnawski Miroslaw , Müller Thorsten G. , Otsuka Shotaro , Hiblot Julien , Koch Birgit , Kueblbeck Moritz , Kräusslich Hans-Georg , Ellenberg Jan , Johnsson Kai 
Published: June 2019

ABSTRACTWe introduce an engineered nanobody whose affinity to green fluorescent protein (GFP) can be switched on and off with small molecules. By controlling the cellular localization of GFP fusion proteins, the engineered nanobody allows to study their role in basic biological processes, an approach that should be applicable to numerous previously described GFP fusions. We also outline how the binding affinities of other nanobodies can be controlled by small molecules.
The advantages of radial trajectories for vessel-selective dynamic angiography with arterial spin labeling
Authors: Berry Eleanor S. K. , Jezzard Peter , Okell Thomas W. 
Published: June 2019

AbstractObjectTo demonstrate the advantages of radial k-space trajectories over conventional Cartesian approaches for accelerating the acquisition of vessel-selective arterial spin labeling (ASL) dynamic angiograms, which are conventionally time-consuming to acquire.Materials and MethodsVessel-encoded pseudocontinuous ASL was combined with time-resolved balanced steady-state free precession (bSSFP) and spoiled gradient echo (SPGR) readouts to obtain dynamic vessel-selective angiograms arising from the four main brain-feeding arteries. Dynamic 2D protocols with acquisition times of one minute or less were achieved through radial undersampling or a Cartesian parallel imaging approach. For whole-brain dynamic 3D imaging, magnetic field inhomogeneity and the high acceleration factors required rule out the use of bSSFP and Cartesian trajectories, so the feasibility of acquiring 3D radial SPGR angiograms was tested.ResultsThe improved SNR efficiency of bSSFP over SPGR was confirmed for 2D dynamic imaging. Radial trajectories had considerable advantages over a Cartesian approach, including a factor of two improvement in the measured SNR (p<0.00001, N=6), improved distal vessel delineation and the lack of a need for calibration data. The 3D radial approach produced good quality angiograms with negligible artifacts despite the high acceleration factor (R=13).ConclusionRadial trajectories outperform conventional Cartesian techniques for accelerated vessel-selective ASL dynamic angiography.
Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in-vivo fetal and neonatal MRI assessment
Authors: Patkee Prachi A. , Baburamani Ana A. , Kyriakopoulou Vanessa , Davidson Alice , Avini Elhaam , Dimitrova Ralica , Allsop Joanna , Hughes Emer , Kangas Johanna , McAlonan Grainne , Rutherford Mary A. 
Published: June 2019

AbstractDown Syndrome (DS) is the most frequent genetic cause of intellectual disability with a wide spectrum of neurodevelopmental outcomes. At present, the relationship between structural brain morphology and the spectrum of cognitive phenotypes in DS, is not well understood. This study aimed to quantify development of the fetal and neonatal brain in DS using dedicated, optimised and motion-corrected in-vivo magnetic resonance imaging (MRI). We detected deviations in development and altered regional brain growth in the fetus with DS from 21 weeks’ gestation, when compared to age-matched controls. Reduced cerebellar volume was apparent in the second trimester with significant alteration in cortical growth becoming evident during the third trimester. Developmental abnormalities in the cortex and cerebellum are likely substrates for later neurocognitive impairment, and ongoing studies will allow us to confirm the role of antenatal MRI as an early biomarker for subsequent cognitive ability in DS. In the era of rapidly developing technologies, it is hoped that the results of this study will assist counselling for prospective parents.
Behavioral training of marmosets and electrophysiological recording from the cerebellum
Authors: Sedaghat-Nejad Ehsan , Herzfeld David J. , Hage Paul , Karbasi Kaveh , Palin Tara , Wang Xiaoqin , Shadmehr Reza 
Published: June 2019

AbstractThe common marmoset (Callithrix Jacchus) is a promising new model for study of neurophysiological basis of behavior in primates. Like other primates, it relies on saccadic eye movements to monitor and explore its environment. Previous reports have demonstrated some success in training marmosets to produce goal-directed actions in the laboratory. However, the number of trials per session has been relatively small, thus limiting the utility of marmosets as a model for behavioral and neurophysiological studies. Here, we report the results of a series of new behavioral training and neurophysiological protocols aimed at increasing the number of trials per session while recording from the cerebellum. To improve the training efficacy, we designed a precisely calibrated food regulation regime that motivated the subjects to perform saccade tasks, resulting in about a thousand reward-driven trials on a daily basis. We then developed a multi-channel recording system that used imaging to target a desired region of the cerebellum, allowing for simultaneous isolation of multiple Purkinje cells in the vermis. In this report, we describe (1) the design and surgical implantation of a CT guided, subject specific head-post, (2) the design of a CT and MRI guided alignment tool for trajectory guidance of electrodes mounted on an absolute encoder microdrive, (3) development of a protocol for behavioral training of subjects, and (4) simultaneous recordings from pairs of Purkinje cells during a saccade task.New and NoteworthyMarmosets present the opportunity to investigate genetically based neurological disease in primates; in particular, diseases that affect social behaviors, vocal communication, and eye movements. All of these behaviors depend on the integrity of the cerebellum. Here, we present training methods that better motivate the subjects, allowing for improved performance, and also present electrophysiological techniques that precisely target the subject’s cerebellum, allowing for simultaneous isolation of multiple Purkinje cells.In our parks, are there any trees more elegant and luxurious than the Purkinje cell from the cerebellum? Santiago Ramon y Cajal
Oropouche virus cases identified in Ecuador using an optimised rRT-PCR informed by metagenomic sequencing
Authors: Wise Emma L. , Márquez Sully , Mellors Jack , Paz Verónica , Atkinson Barry , Gutierrez Bernardo , Zapata Sonia , Coloma Josefina , Pybus Oliver G. , Jackson Simon K. , Trueba Gabriel , Fejer Gyorgy , Logue Christopher H. , Pullan Steven T. 
Published: June 2019

AbstractOropouche virus (OROV) is responsible for outbreaks of Oropouche fever in parts of South America. We recently identified and isolated OROV from a febrile Ecuadorian patient, however, a previously published rRT-PCR assay did not detect OROV in the patient sample. A primer mismatch to the Ecuadorian OROV lineage was identified from metagenomic sequencing data. We report the optimisation of an rRT-PCR assay for the Ecuadorian OROV lineage, which subsequently identified a further five cases in a cohort of 196 febrile patients. We isolated OROV via cell culture and developed an algorithmically-designed primer set for whole-genome amplification of the virus. Metagenomic sequencing of the patient samples provided OROV genome coverage ranging from 68 - 99%. The additional cases formed a single phylogenetic cluster together with the initial case. OROV should be considered as a differential diagnosis for Ecuadorian patients with febrile illness to avoid mis-diagnosis with other circulating pathogens.
Recovery of glutamatergic and GABAergic protein expression in visual cortex after monocular deprivation
Authors: Balsor Justin L. , Jones David G. , Murphy Kathryn M. 
Published: June 2019

AbstractA collection of glutamatergic and GABAergic proteins participate in regulating experience-dependent plasticity in the visual cortex (V1). Many studies have characterized changes to those proteins caused by monocular deprivation (MD) during the critical period (CP), but less is known about changes that occur when MD stops. We measured the effects of 3 types of visual experience after MD (n=24, 10 male and 14 female); reverse occlusion (RO), binocular deprivation (BD), or binocular vision, on the expression of synaptic proteins in V1 including glutamatergic and GABAergic receptor subunits. Synapsin expression was increased by RO but not affected by the other treatments. BD shifted the balance between glutamatergic and GABAergic receptor subunits to favor GABAAα1. In contrast, BV shifted expression to favor the glutamatergic mechanisms by increasing NMDAR and decreasing GABAAα1 subunits. None of the conditions returned normal expression levels to all of the proteins, but BV was the closest.
Variable Mutations at the p53-R273 Oncogenic Hotspot Position Leads to Altered Properties
Authors: Garg A , Hazra J P , Sannigrahi M K , Rakshit S , Sinha S 
Published: June 2019

AbstractMutations in p53 protein, especially in the DNA binding domain is one of the major hallmarks of cancer. The R273 position is a DNA contact position and has several oncogenic variants. Surprisingly, cancer patients carrying different mutant-variants of R273 in p53 have different survival rates indicating that the DNA contact inhibition may not be the sole reason for reduced survival with R273 variants. Here, we probed the structural properties of three major oncogenic variants of the R273: ([R273L], [R273H], and [R273C])p53. Using a series of biophysical, biochemical and theoretical simulation studies, we observe that these oncogenic variants of the p53 not only suffer a loss in DNA binding, but also show distinct structural stabilty, aggregation and toxicity profiles. [R273C]p53 shows maximum amyloidogenicity while [R273L]p53 shows maximum aggregation. Further probe in the aggregation mechanism show that [R273C]p53 aggregation is disulphide mediated whereas hydrophobic interactions dominate self-assembly in [R273L]p53. MD simulation studies clearly show that α-helical intermediates are observed in [R273C]p53 whereas β-sheets are observed for [R273L]p53. Our study indicates that each of the R273 variant has its own distinct property of stability and self-assembly, the molecular basis of which, may lead to different types of cancer pathogenesis in vivo. These studies will aid the design of therapeutic strategies for cancer using residue specific or process specific protein aggregation as target.Statement of significanceThe present work stems from an interesting observation that genetic mutations that results in switching of one amino acid to different variants at the same codon show different cancer cell progression. We are trying to understand the molecular reason behind the different gain-of-function opted by these variants. With the help of biophysical and biochemical experiments, and computational studies we have observed that the different thermal stability, unique mechanism of unfolding and self-assembly might be one of the crucial parameters for their different oncogenic effect. These studies thus call for the need of developing therapeutic strategies that consider the resultant mutant-variant as a target rather than mutation position. This is an important lead towards the understanding of cancer.
Label-free, real-time on-chip sensing of living cancer cell via grating-coupled surface plasmon resonance
Authors: Borile Giulia , Rossi Stefano , Filippi Andrea , Gazzola Enrico , Capaldo Pietro , Tregnago Claudia , Pigazzi Martina , Romanato Filippo 
Published: June 2019

ABSTRACTThe application of nanotechnologies to address biomedical questions is a key strategy for innovation in biomedical research. Among others, a key point consists in the availability of nanotechnologies for monitoring cellular processes in a real-time and label-free approach. Here, we focused on a grating-coupled Surface Plasmon Resonance (GC-SPR) sensor exploiting phase interrogation. This sensor can be integrated in a microfluidic chamber that ensures cell viability and avoids cell stress. We report the calibration of the sensor response as a function of cell number and its application to monitor cell adhesion kinetics as well as cell response to an external stimulus. Our results show that GC-SPR sensors can offer a valuable alternative to prism-coupled or imaging SPR devices, amenable for microfluidic implementation.
Microenvironment-contextual cell signaling is attenuated with age
Authors: Ertsås Henriette C. , LaBarge Mark A. , Lorens James B 
Published: June 2019

AbstractPost-menopausal women are more prone to breast cancer than younger women. The increased frequency of age-related breast cancers is likely due to interactions between acquired mutations and age-dependent epigenetic changes that affect mammary epithelial lineage fidelity. We hypothesized that the aging process fundamentally affects how human mammary epithelial cells (HMEC) respond to microenvironmental signals, resulting in increased susceptibility to oncogenic transformation. In order to measure microenvironmental cell signaling in normal finite lifespan HMEC, we applied a novel microsphere-based flow cytometry technology. The microsphere cytometry allows multiparametric single cell quantification of signaling pathway activity and lineage-specific marker expression in cells adhered to surface-functionalized microspheres that mimic specific microenvironments. Using this approach, we analyzed age-dependent changes in human mammary myoepithelial and luminal epithelial cells exposed to different ECM and growth factors. We found that ECM–mediated MAP kinase and PI3 kinase activation levels in HMEC were attenuated with age. Older luminal cells displayed higher surface integrin levels consistent with acquired basal identity, albeit with decreased integrin activation and increased Src-signaling relative to myoepithelial cells. We show that the diminished signaling magnitude in HMEC from older women correlated with reduced probability of activating oncogene-induced senescence. We propose that age-related changes in ECM-mediated epithelial cell regulation may impair protective tumor suppression mechanisms and increase breast cancer susceptibility.
Evaluating service quality in automobile maintenance and repair industry
Authors: Jain Nikunj Kumar , Singh Alok Kumar , Kaushik Kapil 
Published: June 2019

PurposeThe purpose of this paper is to analyse service quality in the automobile maintenance and repair industry. A conceptual structural model is developed to investigate the impact of service quality, perceived service fairness and convenience on customer service satisfaction. The impact of service satisfaction and brand trust on word of mouth (WOM) is also explored, and the study assesses the mediating effect of customer service satisfaction on the relationship between service quality and WOM.Design/methodology/approachData from a questionnaire-based survey of 259 users of automobile maintenance and repair centres were analysed using covariance-based structural equation modelling.FindingsThe findings indicate that service quality dimensions (reliability, responsiveness and empathy), perceived service fairness and convenience are positively associated with customer service satisfaction, and that service satisfaction and trust positively influence WOM. The findings support the mediating effect of service satisfaction on the relationship between reliability and responsiveness and WOM.Research limitations/implicationsThe study’s main limitation is the cross-sectional design, which limits the generalisability of the findings.Practical implicationsTo ensure customer satisfaction and generate trust and WOM, automobile maintenance and repair service centres should improve reliability, responsiveness and empathy, as well as perceived service fairness and convenience.Originality/valueThe study demonstrates that the reliability and responsiveness dimensions of service quality are the most significant predictors of customer service satisfaction in the automobile maintenance and repair industry.