bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated prevalence of azole resistant Aspergillus fumigatus in urban versus rural environments in the United Kingdom
Authors: Sewell Thomas R , Zhang Yuyi , Brackin Amelie P , Shelton Jennifer MG , Rhodes Johanna , Fisher Matthew C 
Published: April 2019

AbstractAzole resistance in the opportunistic pathogen Aspergillus fumigatus is increasing, dominated primarily by two environmentally-associated resistance alleles: TR34/L98H and TR46/Y121F/T289A. Using an environmental sampling strategy across the South of England we assess the prevalence of azole resistant A. fumigatus (ARAf) in soil samples collected in both urban and rural locations. We characterise the susceptibility profiles of the resistant isolates to three medical azoles, identify the underlying genetic basis of resistance and investigate their genetic relationships. ARAf was detected in 6.7% of the soil samples, with a higher prevalence in urban (13.8%) compared to rural (1.1%) locations. Nineteen isolates were confirmed to exhibit clinical breakpoints for resistance to at least one of three medical azoles, with 18 isolates exhibiting resistance to itraconazole, four to voriconazole, with two also showing additional elevated minimum inhibitory concentration to posaconazole. Thirteen of the resistant isolates harboured the TR34/L98H resistance allele and six isolates carried TR46/Y121F/T289A allele. The 19 azole-resistant isolates were spread across five csp1 genetic subtypes, t01, t02, t04B, t09 and t18 with t02 the predominant subtype. Our study demonstrates that ARAf can be easily isolated in the South of England, especially in urban city centres, which appear to play an important role in the epidemiology of environmentally-linked drug resistant A. fumigatus.
Within-finger maps of tactile and nociceptive input in the human parietal cortex
Authors: Mancini Flavia , Sereno Martin I. , Lee Min-Ho , Iannetti Giandomenico D , Tracey Irene 
Published: April 2019

AbstractThe spatial representation of nociceptive input in the human parietal cortex is not fully understood. For instance, it is known that the primary somatosensory cortex (S1) contains a representation of nociceptive-selective input to different fingers, but it is unclear whether S1 subdivisions contain finer-grained, within-finger maps of nociceptive input. It is also unknown whether within-finger maps of somatosensory input exist in intraparietal regions. Therefore, we used high-field 7T functional MRI to reveal within-finger maps of nociceptive and tactile inputs in the human parietal cortex. Although we replicated the previous findings of between-finger maps of nociceptive input spanning S1 subdivisions, we found weak and inconsistent evidence for within-finger maps of nociceptive input in S1 subdivisions. In the same subjects, we found mirrored, within-finger maps of tactile input in areas 3a, 3b, and 1. Importantly, we discovered a within-finger map of nociceptive input, but not of tactile input, in the human intraparietal area 1 (hIP1). In conclusion, our study indicates that the spatial representation of nociceptive input in the parietal cortex partly differs from that of tactile input and reports the discovery of a within-finger map of nociceptive input in hIP1.New & NoteworthyWe report the discovery of a fine-grained map of nociceptive input to finger segments in the human intraparietal area 1.
Basal ganglia contributions during the learning of a visuomotor rotation: effect of dopamine, deep brain stimulation and reinforcement
Authors: Singh Puneet , Lenka Abhishek , Stezin Albert , Jhunjhunwala Ketan , Pal Pramod Kumar , Ghosal Ashitava , Murthy Aditya 
Published: April 2019

AbstractIt is commonly thought that visuomotor adaptation is mediated by the cerebellum while reinforcement learning is mediated by the basal ganglia. In contrast to this strict dichotomy, we demonstrate a role for the basal ganglia in visuomotor adaptation (error-based motor learning) in patients with Parkinson’s disease (PD) by comparing the degree of motor learning in the presence and absence of dopamine medication. We further show similar modulation of learning rates in the presence and absence of subthalamic deep brain stimulation. We also report that reinforcement is an essential component of visuomotor adaptation by demonstrating the lack of motor learning in patients with PD during the ON-dopamine state relative to the OFF-dopamine state in the absence of a reinforcement signal. Taken together, these results suggest that the basal ganglia modulate the gain of visuomotor adaptation based on the reinforcement received at the end of the trial.
Diminution of feeding response in Helicoverpa armigera by inhibition or silencing of sugar gustatory receptor
Authors: Agnihotri Aniruddha R. , Zunjarrao Sanyami S. , Nagare Mukta , Joshi Rakesh S. 
Published: April 2019

ABSTRACTGustatory receptor (GR) is one of the essential chemosensory molecules in Lepidopteran pests. GR is involved in sensing several canonical tastes which in turn regulate the diverse behavioral and physiological responses of these insects. In this article, we have evaluated the alteration in feeding response of Helicoverpa armigera by blocking and silencing of sugar-sensing gustatory receptor 9 (HarmGr9). Sf9 cells based assay showed that glucose analogue, Miglitol, can bind to the expressed HarmGr9. This binding might lead to an inhibition of receptor activation and downstream signaling, indicated by reduced intracellular Ca2+ fluorescence. Further, the in-vivo study illustrated the feeding rate reduced on a diet containing miglitol as compared to the larvae fed on the artificial diet. Reduction in feeding rate was prolonged in insects fed on the miglitol containing diet even after switching to the control glucose diet. Competitive cell-based assay and feeding assay, using equimolar glucose and miglitol, also showed an inhibitory effect on HarmGr-9 activation and insect feeding rate. We have observed similar feeding rate reduction in HarmGr9 knockdown in H. armigera larvae. We believe this unique approach of H. armigera feeding response inhibition by blocking the sugar receptor can be further used to develop a novel strategy for agricultural pest management.
A passive, camera-based head-tracking system for real-time, 3D estimate of head position and orientation in rodents
Authors: Vanzella Walter , Grion Natalia , Bertolini Daniele , Perissinotto Andrea , Zoccolan Davide 
Published: April 2019

AbstractTracking head’s position and orientation of small mammals is crucial in many behavioral neurophysiology studies. Yet, full reconstruction of the head’s pose in 3D is a challenging problem that typically requires implanting custom headsets made of multiple LEDs or inertial units. These assemblies need to be powered in order to operate, thus preventing wireless experiments, and, while suitable to study navigation in large arenas, their application is unpractical in the narrow operant boxes employed in perceptual studies. Here we propose an alternative approach, based on passively imaging a 3D-printed structure, painted with a pattern of black dots over a white background. We show that this method is highly precise and accurate and we demonstrate that, given its minimal weight and encumbrance, it can be used to study how rodents sample sensory stimuli during a perceptual discrimination task and how hippocampal place cells represent head position over extremely small spatial scales.
RNAi screen reveals a role for PACSIN2 and caveolins during bacterial cell-to-cell spread
Authors: Sanderlin Allen G. , Vondrak Cassandra , Scricco Arianna J. , Fedrigo Indro , Ahyong Vida , Lamason Rebecca L. 
Published: April 2019

AbstractListeria monocytogenes is a human bacterial pathogen that disseminates through host tissues using a process called cell-to-cell spread. This critical yet understudied virulence strategy resembles a vesicular form of intercellular trafficking that allows L. monocytogenes to move between host cells without escaping the cell. Interestingly, eukaryotic cells can also directly exchange cellular components via intercellular communication pathways (e.g. trans-endocytosis) using cell-cell adhesion, membrane trafficking, and membrane remodeling proteins. Therefore, we hypothesized that L. monocytogenes would hijack these types of host proteins during spread. Using a focused RNAi screen, we identified 22 host genes that are important for L. monocytogenes spread. We then found that caveolins (CAV1 and CAV2) and the membrane sculpting F-BAR protein PACSIN2 promote L. monocytogenes protrusion engulfment during spread, and that PACSIN2 specifically localized to protrusions. Overall, our study demonstrates that host intercellular communication pathways may be co-opted during bacterial spread and that specific trafficking and membrane remodeling proteins promote bacterial protrusion resolution.SummaryThe human bacterial pathogen Listeria monocytogenes disseminates through host tissues using a process called cell-to-cell spread. In this study, Sanderlin et al., discover that host proteins that normally regulate membrane trafficking and membrane remodeling in uninfected settings are also co-opted by Listeria to promote spread.
Negative Binomial Additive Model for RNA-Seq Data Analysis
Authors: Ren Xu , Kuan Pei Fen 
Published: April 2019

SUMMARYHigh-throughput sequencing experiments followed by differential expression analysis is a widely used approach for detecting genomic biomarkers. A fundamental step in differential expression analysis is to model the association between gene counts and co-variates of interest. Existing models assume linear effect of covariates, which is restrictive and may not be sufficient for some phenotypes. In this paper, we introduce NBAMSeq, a flexible statistical model based on the generalized additive model and allows for information sharing across genes in variance estimation. Specifically, we model the logarithm of mean gene counts as sums of smooth functions with the smoothing parameters and coefficients estimated simultaneously within a nested iterative method. The variance is estimated by the Bayesian shrinkage approach to fully exploit the information across all genes. Based on extensive simulation and case studies of RNA-Seq data, we show that NBAMSeq offers improved performance in detecting nonlinear effect and maintains equivalent performance in detecting linear effect compared to existing methods. Our proposed NBAMSeq is available for download athttps://github.com/reese3928/NBAMSeqand in submission to Bioconductor repository.
Quantifying the mechanics of locomotion of the schistosome pathogen with respect to changes in its physical environment
Authors: Zhang Shun , Skinner Danielle , Joshi Prateek , Criado-Hidalgo Ernesto , Yeh Yi-Ting , Lasheras Juan C. , Caffrey Conor R. , Alamo Juan C. del 
Published: April 2019

AbstractSchistosomiasis is a chronic and morbid disease of poverty affecting approximately 200 million people worldwide. Mature schistosome flatworms wander in the host’s hepatic portal and mesenteric venous system where they encounter a range of blood flow conditions and geometrical confinement. However, the mechanisms that support schistosome locomotion and underlie the pathogen’s adaptation to its physical environment are largely unknown. By combining microfabrication and traction force microscopy, we developed various in vitro assays to quantify the mechanics of locomotion of adult male S. mansoni in different physiologically relevant conditions. We show that in unconfined settings, the parasite undergoes two-anchor marching mediated by the coordinated action of its oral and ventral suckers. This mode of locomotion is maintained when the worm faces an external flow, to which it responds by adjusting the strength of its suckers. In geometrically confined conditions, S. mansoni switches to a different crawling modality by generating retrograde peristaltic waves along its body, a mechanism shared with terrestrial and marine worms. But while the surface of most worms has backward-pointing bristles that rectify peristaltic waves and facilitate forward locomotion, S mansoni has isotropically oriented tubercles. This requires tight coordination between muscle contraction and substrate friction but confers S. mansoni the ability to reverse its direction of locomotion without turning its body, which is likely advantageous to maneuver in narrow bore vessels. We show that the parasite can also coordinate the action of its suckers with its peristaltic body contractions to increase crawling speed. Throughout this study, we report on a number of biomechanical parameters to quantify the motility of adult schistosomes (e.g. sucker grabbing strength, rate of detachment under flow, peristaltic wave properties and traction stresses). The new series of in vitro assays make it possible to quantify key phenotypical aspects of S. mansoni motility that could guide the discovery of new drugs to treat schistosomiasis.
Associatively-mediated suppression of corticospinal excitability: A transcranial magnetic stimulation (TMS) study
Authors: Seet Manuel S. , Livesey Evan J. , Harris Justin A. 
Published: April 2019

AbstractResponse inhibition—the suppression of prepotent behaviours when they are inappropriate— has been thought to rely on executive control. Against this received wisdom, it has been argued that external cues repeatedly associated with response inhibition can come to trigger response inhibition automatically without top-down command. The current project endeavoured to provide evidence for associatively-mediated motor inhibition. We tested the hypothesis that stop-associated stimuli can, in a bottom-up fashion, directly activate inhibitory mechanisms in the motor cortex. Human subjects were first trained on a stop-signal task. Once trained, the subjects received transcranial magnetic stimulation applied over their primary motor cortex during passive observation of either the stop signal (i.e. without any need to stop a response) or an equally familiar control stimulus never associated with stopping. Analysis of motor-evoked potentials showed that corticospinal excitability was reduced during exposure to the stop signal, which likely involved stimulus-driven activation of intracortical GABAergic interneurons. This result offers evidence for the argument that, through associative learning, stop-associated stimuli can engage local inhibitory processes at the level of the motor cortex.
Linking molecular pathways and large-scale computational modeling to assess candidate disease mechanisms and pharmacodynamics in Alzheimer’s disease
Authors: Stefanovski Leon , Triebkorn Paul , Spiegler Andreas , Diaz-Cortes Margarita-Arimatea , Solodkin Ana , Jirsa Viktor , McIntosh Anthony Randal , Ritter Petra ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2019

AbstractIntroductionWhile the prevalence of neurodegenerative diseases associated with dementia such as Alzheimer’s disease (AD) increases, our knowledge on the underlying mechanisms, outcome predictors, or therapeutic targets is limited. In this work, we demonstrate how computational multi-scale brain modelling links phenomena of different scales and therefore identifies potential disease mechanisms leading the way to improved diagnostics and treatment.MethodsThe Virtual Brain (TVB; thevirtualbrain.org) neuroinformatics platform allows standardized large-scale structural connectivity-based simulations of whole brain dynamics. We provide proof of concept for a novel approach that quantitatively links the effects of altered molecular pathways onto neuronal population dynamics. As a novelty, we connect chemical compounds measured with positron emission tomography (PET) with neural function in TVB addressing the phenomenon of hyperexcitability in AD related to the protein amyloid beta (Abeta). We construct personalized virtual brains based on individual PET derived distributions of Abeta in patients with mild cognitive impairment (MCI, N=8) and Alzheimer’s Disease (AD, N=10) and in age-matched healthy controls (HC, N=15) using data from ADNI-3 data base (http://adni.lni.usc.edu). In the personalized virtual brains, individual Abeta burden modulates regional inhibition, leading to disinhibition and hyperexcitation with high Abeta loads. We analyze simulated regional neural activity and electroencephalograms (EEG).ResultsKnown empirical alterations of EEG in patients with AD compared to HCs were reproduced by simulations. The virtual AD group showed slower frequencies in simulated local field potentials and EEG compared to MCI and HC groups. The heterogeneity of the Abeta load is crucial for the virtual EEG slowing which is absent for control models with homogeneous Abeta distributions. Slowing phenomena primarily affect the network hubs, independent of the spatial distribution of Abeta. Modeling the N-methyl-D-aspartate (NMDA) receptor antagonism of memantine in local population models, reveals potential functional reversibility of the observed large-scale alterations (reflected by EEG slowing) in virtual AD brains.DiscussionWe demonstrate how TVB enables the simulation of systems effects caused by pathogenetic molecular candidate mechanisms in human virtual brains.
Mid-lateral Cerebellar Purkinje Cells Provide a Cognitive Error Signal When Monkeys Learn a New Visuomotor Association
Authors: Sendhilnathan Naveen , Ipata Anna E. , Goldberg Michael E. 
Published: April 2019

AbstractHow do we learn to establish associations between arbitrary visual cues (like a red light) and movements (like braking the car)? We investigated the neural correlates of visuomotor association learning in the monkey mid-lateral cerebellum. Here we show that, during learning but not when the associations were overlearned, individual Purkinje cells reported the outcome of the monkey’s most recent decision, an error signal, which was independent of changes in hand movement or reaction time. At the population level, Purkinje cells collectively maintained a memory of the most recent decision throughout the entire trial period, updating it after every decision. This error signal decreased as the performance improved. Our results suggest a role of mid-lateral cerebellum in visuomotor associative learning and provide evidence that cerebellum could be a generalized learning system, essential in non-motor learning as well as motor learning.
iRhom2 serves as a facilitator in obesity by enhancing adipose inflammation and insulin resistance
Authors: Minxuan Xu , Chenxu Ge , Yuting Qin , Deshuai Lou , Qiang Li , Jing Feng , Yekuan Wu , Linfeng Hu , Ping Huang , Jun Tan 
Published: April 2019

AbstractChronic inflammation of adipose tissues contributes to obesity-triggered insulin resistance. Unfortunately, the potential molecular mechanisms regarding obesity associated systemic inflammation and metabolic disorder remain complicated. Here we display that inactive rhomboid-like protein 2 (iRhom2) is increased in mice fat with adipose inflammation. After 16 weeks on a high fat diet (HFD), obesity, chronic inflammation in adipose tissues and insulin resistance are markedly mitigated in iRhom2-knockout (iRhom2 KO) mice, but exaggerated in iRhom2-overactivated mice. The adverse impressions of iRhom2 on adipose inflammation and associated pathologies are determined in db/db mice. Also, we further exhibit that in response to HFD, iRhom2 KO mice and mice with deletion only in myeloid cells showed less severe adipose inflammation and insulin resistance than the control groups. Conversely, transplantation of bone marrow cells from normal mice to iRhom2 KO mice unleashed the severity of systemic inflammation and metabolic dysfunction after HFD ingestion. In conclusion, we identify iRhom2 as a key regulator that promotes obesity-associated metabolic disorder. Loss of iRhom2 from macrophages in adipose tissues inhibited the inflammation and insulin resistance. iRhom2 might be a therapeutic target for obesity-induced metabolic dysfunction.SignificanceIncreased inactive rhomboid-like protein 2 signaling has recently been shown to trigger inflammation-associated activation of innate immune responses. Herein we investigate that this signal also plays a crucial role in obesity-triggered adipose tissue inflammation infiltration and metabolic disorder, beyond the well-known assignment in innate immune supervision. Also, we have reported the iRhom2 as a key promoter in regulating metabolic function, which enhances obesity-stimulated inflammation and systemic insulin resistance by up regulation of macrophages pro-inflammatory activation. Our current study indicates that targeting the iRhom2 signaling in adipose tissues could possibly be an efficient strategy to mitigating obesity-associated systemic inflammation and metabolic dysfunction.
BIM-based draft schedule generation in reinforced concrete-framed buildings
Authors: Wang Ziwei , Rezazadeh Azar Ehsan 
Published: April 2019

Purpose
Project schedules have a vital role in the effective management of time, cost, scope and resources in construction projects, and creating schedules requires schedulers with construction knowledge and experience. The increase in the complexity of building projects and the emergence of building information modeling (BIM) in the architecture, engineering and construction industry have encouraged researchers to explore BIM capabilities for automated schedule generation. The scope and capabilities of the developed systems, however, are limited and the link between design and scheduling is still underdeveloped. This paper aims to investigate methods to develop a BIM-based framework to automatically generate schedules for concrete-framed buildings.

Design/methodology/approach
This system first extracts the required data from the building information model, including elements’ dimensions, quantities, spatial information, materials and other related attributes. It then applies construction rules, prior knowledge and production rate data to create project work-packages, calculate their durations and determine their relationships. Finally, it organizes these results into a schedule using project management software.

Findings
This system provides an automated and easy-to-use approach to generate schedules for concrete-framed buildings that are modeled in a BIM platform. It provides two schedules for each project, both a sequential and an overlapped solution, which the schedulers can modify into a practical schedule based on conditions and available resources.

Originality/value
This research project presents an innovative approach to use BIM-based attributes of structural elements to develop list of work-packages and estimate their durations, and then it uses a combination of rule-based and case-based reasoning to generate the schedules.