bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lyb-2-4, a unique genomic region of hypervirulent carbapenem-resistant Acinetobacter baumannii
Authors: Zheng Chao , Zhang Jinyong , Zhang Min , Liu Zhou , Zhong Yuxin , Liu Shiyi , Cui Ruiqin , Deng Qiuyang , Xu Yanji , Shi Yun , Zeng Hao , Yang Xiyao , Lin Chuchu , Luo Yutian , Chen Huaisheng , Wu Weiyuan , Wu Jinsong , Zhang Tianle , Lu Yuemei , Liu Xueyan , Zou Quanming , Huang Wei 
Published: September 2019

ABSTRACTAcinetobacter baumannii is an important human pathogen due to its multi-drug resistance, but is usually with low-grade virulence. Although a mouse model revealed different virulence grades of clinical carbapenem-resistant A. baumannii (CRAB) strains, the genetic basis remains unknown. We collected 61 CRAB isolates from intensive care unit of Shenzhen People’s Hospital (Shenzhen, China), and analyzed them used whole genome sequencing (WGS), multilocus sequence typing (MLST) and core genome MLST (cgMLST), transmission chain reconstruction and Comparative genomic tools. A mouse pneumonia model was used to confirm the hypervirulent phenotype. Eleven complex types (CT) were identified based on core genome multilocus sequence typing scheme. CT512 showed higher transmissibility and bloodstream infection rates than other CTs. A genomic region Lyb-2-4 was shared by CT512 and CT2092 but not CT2085. The mortality rates of patient infected with CRAB harboring Lyb-2-4 was significantly higher than those infected with CRAB isolates without Lyb-2-4 (77.8% vs 24.5%, p < 0.01). In the mouse model, the survival rates of strains containing the Lyb-2-4 region (LAC-4, 5122 and 2092) were significantly lower than for strains without Lyb-2-4 (7152, 71517, 20859 and ATCC17978). One open reading frame (ORF) was a marker for the presence of Lyb-2-4, and PCR of a segment of this ORF, designated as hvcT, served as a tag for hypervirulent CRAB. Our study should be very useful in advising the clinician to implement medical intervention earlier, and also making the worldwide surveillance of these hypervirulent CRAB strains easier.IMPORTANCEHypervirulent CRAB strains are expected to pose a threat to human health because infection of these strains is associated with high mortality and multidrug resistance. The rapid hypervirulent CRAB identification assay will facilitate prompt medical intervention. Our findings should provoke surveillance for hypervirulent CRAB strains harboring Lyb-2-4 in other countries. Further research should focus on the mechanism of hypervirulence, the acquisition of this genomic region and the development of control measures to prevent further dissemination.
Intraspecific trait variability and community assembly in hawkmoths (Lepidoptera:Sphingidae) across an elevational gradient in the eastern Himalayas, India
Authors: Mungee Mansi , Athreya Ramana 
Published: September 2019

AbstractRecent progress in functional ecology has advanced our understanding of the role of intraspecific (ITV) and interspecific (STV) trait variation in community assembly across environmental gradients. Studies on plant communities have generally found STV as the main driver of community trait variation, whereas ITV plays an important role in determining species co-existence and community assembly. However, similar studies of faunal taxa, especially invertebrates, are very few in number.We investigated variation of hawkmoth (Lepidoptera:Sphingidae) traits along an environmental gradient spanning 2600 m in the eastern Himalayas and its role in community assembly, using the morpho-functional traits of body mass (BM), wing loading (WL) and wing aspect ratio (AR).We employ the recently proposedT-statisticsto test for non-random assembly of hawkmoth communities and the relative importance of the two opposing forces for trait divergence (internal filters) and convergence (external filters).Community-wide trait-overlap decreased for all three traits with increasing environmental distance, suggesting the presence of elevation specific optimum morphology (i.e. functional response traits). Community weighted mean of BM and AR increased with elevation. Overall, the variation was dominated by species turnover but ITV accounted for 25%, 23% and <1% variability of BM, WL and AR, respectively. T-statistics, which incorporates ITV, revealed that elevational communities had a non-random trait distribution, and that community assembly was dominated by internal filtering throughout the gradient.This study was carried out using easily measurable morpho-traits obtained from calibrated field images of a large number (3301) of individuals. That these also happened to be important environmental response traits resulted in a significant signal in the metrics that we investigated. Such studies of abundant and hyperdiverse invertebrate groups across large environmental gradients should considerably improve our understanding of community assembly processes.
Genetic correlations across genetically determined and developmentally plastic alternative reproductive tactics
Authors: Abbott Jessica K. , Rios-Cardenas Oscar , Morris Molly 
Published: September 2019

AbstractAlternative reproductive tactics occur when individuals of the same sex have a suite of morphological and/or behavioural traits that allow them to pursue different reproductive strategies. A common pattern is e.g. the existence of “courter” and “sneaker” tactics within males. We have previously argued that alternative reproductive tactics should be subject to genetic conflict over the phenotypic expression of traits, similar to sexual antagonism. In this process, which we called intra-locus tactical conflict, genetically determined tactics experience conflicting selection on a shared phenotypic trait, such as body size, but a positive genetic correlation between tactics in body size prevents either tactic from reaching its optimum. Recently, other authors have attempted to extend this idea to developmentally plastic alternative reproductive tactics, with mixed results. However, it is not clear whether we should expect intra-locus tactical conflict in developmentally plastic tactics or not. We have therefore run a series of simulation models investigating under what conditions we should expect to see positive estimates of the inter-tactical genetic correlation, since a positive genetic correlation is a prerequisite for the existence of intra-locus tactical conflict. We found that for autosomal, X-linked, and Y-linked genetically-determined tactics, estimated inter-tactical genetic correlations were generally high. However, for developmentally plastic tactics, the genetic correlation depends on the properties of the switching threshold between tactics. If it is fixed, then estimated genetic correlations are positive, but if there is genetic variation in the switch-point, then any sign and magnitude of estimated genetic correlation is possible, even for highly heritable traits where the true underlying correlation is perfect. This means that caution should be used when investigating genetic constraints in plastic phenotypes.
StemBond hydrogels optimise the mechanical microenvironment for embryonic stem cells
Authors: Labouesse Céline , Agley Chibeza C. , Tan Bao Xiu , Hofer Moritz , Winkel Alex , Stirparo Giuliano G. , Stuart Hannah T. , Verstreken Christophe M. , Mansfield William , Bertone Paul , Franze Kristian , Silva Jose C. R. , Chalut Kevin J. 
Published: September 2019

ABSTRACTStudies of mechanical signalling are typically performed by comparing cells cultured on soft and stiff hydrogel-based substrates. However, it is challenging to independently and robustly control both substrate stiffness and tethering of extracellular matrix (ECM) to substrates, making ECM tethering a potentially confounding variable in mechanical signalling investigations. Moreover, poor ECM tethering can lead to weak cell attachment. To address this, we developed StemBond hydrogels, a hydrogel formulation in which ECM tethering is stable and can be varied independently of stiffness. We show that soft StemBond hydrogels provide an optimal format for culturing embryonic stem (ES) cells. We find that soft StemBond substrates improve the homogeneity of ES cell populations, boost their self-renewal, and increase the efficiency of cellular reprogramming. Our findings underline how soft microenvironments impact mechanosensitive signalling pathways regulating self-renewal and differentiation, indicating that optimising the complete mechanical microenvironment will offer greater control over stem cell fate specification.
Will an outbreak exceed available resources for control? Estimating the risk from invading pathogens using practical definitions of a severe epidemic
Authors: Thompson R.N. , Gilligan C.A. , Cunniffe N.J. 
Published: September 2019

ABSTRACTForecasting whether or not initial reports of disease will be followed by a severe epidemic is an important component of disease management. Standard epidemic risk estimates involve assuming that infections occur according to a branching process and correspond to the probability that the outbreak persists beyond the initial stochastic phase. However, an alternative assessment is to predict whether or not initial cases will lead to a severe epidemic in which available control resources are exceeded. We show how this risk can be estimated by considering three practically relevant potential definitions of a severe epidemic; namely, an outbreak in which: i) a large number of hosts are infected simultaneously; ii) a large total number of infections occur; and iii) the pathogen remains in the population for a long period. We show that the probability of a severe epidemic under these definitions often coincides with the standard branching process estimate for the major epidemic probability. However, these practically relevant risk assessments can also be different from the major epidemic probability, as well as from each other. This holds in different epidemiological systems, highlighting that careful consideration of what constitutes a severe epidemic in an ongoing outbreak is vital for accurate risk quantification.
Rich polymorphic variants of alpha satellite 34mer higher order repeats in hg38 assembly of human chromosome Y
Authors: Vlahović Ines , Glunčić Matko , Paar Vladimir 
Published: September 2019

AbstractA challenging problem in human population genetics is related to the unique role of human Y chromosome, with properties that distinguish humans from other species. Centromeres in primate genomes are constituted of tandem repeats of ∼ 171 bp alpha satellite monomers, commonly organized into higher order repats (HORs). Because of gaps in DNA sequencing, HOR regions as genomic “black holes” have been understudied in spite of crucial importance. Only recently the sequencing of more complete satellite DNAs becomes accessible. In human Y chromosome the largest alpha satellite higher order repeat unit 34/36mer was found, but its polymorphic variants were not investigated. Here, we study the human Y chromosome centromeric genomic sequence from hg38 assembly using our novel ALPHAsub algorithm for simple identification of alpha satellite arrays and robust GRM algorithm for HOR identification in repeat sequences. We determine the monomer alignment scheme for alpha satellite HOR array based on canonical 34mer HOR, discovering a wealth of novel polymorphic variants which include the HOR-type monomer duplications, monomer deletions/insertions or rearrangements and non-HOR insertions.Author SummaryThe centromere is important for segregation of chromosomes during cell division in eukaryotes. Its destabilization results in chromosomal missegregation, aneuploidy, hallmarks of cancers and birth defects. In primate genomes centromeres contain tandem repeats of ∼ 171 bp alpha satellite DNA, commonly organized into higher order repeats (HORs). In this work, we used our bioinformatics algorithms to study the human Y chromosome centromeric genomic sequence and we discover a wealth of novel polymorphic variants which include the HOR-type monomer duplications, monomer deletions/insertions or rearrangements and non-HOR insertions. These results could help to understand the role of alpha satellites and alpha HOR structures in centromeric organization and function, in particular their role in creating a functional kinetochore that is crucial for chromosome segregation during cell division.
Activation of specific mushroom body output neurons inhibits proboscis extension and feeding behavior
Authors: Chia Justine , Scott Kristin 
Published: September 2019

AbstractThe ability to modify behavior based on prior experience is essential to an animal’s survival. For example, animals may become attracted to a previously neutral odor or reject a previously appetitive food source upon learning. In Drosophila, the mushroom bodies (MBs) are critical for olfactory associative learning and conditioned taste aversion, but how the output of the MBs affects specific behavioral responses is unresolved. In conditioned taste aversion, Drosophila shows a specific behavioral change upon learning: proboscis extension to sugar is reduced after a sugar stimulus is paired with an aversive stimulus. While studies have identified MB output neurons (MBONs) that drive approach or avoidance behavior, whether the same MBONs impact proboscis extension behavior is unknown. Here, we tested the role of MB pathways in modulating proboscis extension and identified 10 MBON split-GAL4 lines that upon activation significantly decreased proboscis extension to sugar. Activating several of these lines also decreased sugar consumption, revealing that these MBONs have a general role in modifying feeding behavior beyond proboscis extension. Although the MBONs that decreased proboscis extension and ingestion are different from those that drive avoidance behavior in another context, the diversity of their arborizations demonstrates that a distributed network influences proboscis extension behavior. These studies provide insight into how the MB flexibly alters the response to taste compounds and modifies feeding decisions.
Convergence of unisensory-evoked signals via multiple pathways to the cerebellum
Authors: Shimuta Misa , Sugihara Izumi , Ishikawa Taro 
Published: September 2019

SUMMARYThe cerebellum receives signals directly from peripheral sensory systems and indirectly from the neocortex. To reveal how these different types of signals are processed in the cerebellar cortex,in vivowhole-cell recordings from granule cells and unit recordings from Purkinje cells were performed in mice in which primary somatosensory cortex (S1) could be optogenetically inhibited. Tactile stimulation of the upper lip produced two-phase granule cell responses (with latencies of ∼ 8 ms and 28 ms), for which only the late phase was S1 dependent. Complex spikes and the late phase of simple spikes in Purkinje cells were also S1 dependent. These results indicate that individual granule cells integrate convergent inputs from the periphery and neocortex, and send their outputs to Purkinje cells, which then combine those signals with climbing fiber signals from the neocortex.
Longitudinal Changes of Resting-State Functional Connectivity of Amygdala Following Fear Learning and Extinction
Authors: Martynova Olga , Tetereva Alina , Balaev Vladislav , Portnova Galina , Ushakov Vadim , Ivanitsky Alexey 
Published: September 2019

AbstractAltered functional connectivity of the amygdala has been observed in a resting state immediately after fear learning, even one day after aversive exposure. The persistence of increased resting-state functional connectivity (rsFC) of the amygdala has been a critical finding in patients with stress and anxiety disorders. However, longitudinal changes in amygdala rsFC have rarely been explored in healthy participants. To address this issue, we studied the rsFC of the amygdala in two groups of healthy volunteers. The control group participated in three fMRI scanning sessions of their resting state at the first visit, one day, and one week later. The experimental group participated in three fMRI sessions on the first day: a resting state before fear conditioning, a fear extinction session, and a resting state immediately after fear extinction. Furthermore, this group experienced scanning after one day and week. The fear-conditioning paradigm consisted of visual stimuli with a distinct rate of partial reinforcement by electric shock. During the extinction, we presented the same stimuli in another sequence without aversive pairing. In the control group, rsFC maps were statistically similar between sessions for the left and right amygdala. However, in the experimental group, the increased rsFC mainly of the left amygdala was observed after extinction, one day, and one week. The between-group comparison also demonstrated an increase in the left amygdala rsFC in the experimental group. Our results indicate that functional connections of the left amygdala influenced by fear learning may persist for several hours and days in the human brain.
Physics-based predictive simulations to explore the differential effects of motor control and musculoskeletal deficits on gait dysfunction in cerebral palsy: a retrospective case study
Authors: Falisse Antoine , Pitto Lorenzo , Kainz Hans , Hoang Hoa , Wesseling Mariska , Van Rossom Sam , Papageorgiou Eirini , Bar-On Lynn , Hallemans Ann , Desloovere Kaat , Molenaers Guy , Van Campenhout Anja , De Groote Friedl , Jonkers Ilse 
Published: September 2019

ABSTRACTModel-based simulations of walking have the theoretical potential to support clinical decision making by predicting the functional outcome of treatments in terms of walking performance. Yet before using such simulations in clinical practice, their ability to identify the main treatment targets in specific patients needs to be demonstrated. In this study, we generated predictive simulations of walking with a medical imaging based neuro-musculoskeletal model of a child with cerebral palsy presenting crouch gait. We explored the influence of altered muscle-tendon properties, reduced neuromuscular control complexity, and spasticity on gait function in terms of joint kinematics, kinetics, muscle activity, and metabolic cost of transport. We modeled altered muscle-tendon properties by personalizing Hill-type muscle-tendon parameters based on data collected during functional movements, simpler neuromuscular control by reducing the number of independent muscle synergies, and spasticity through delayed muscle activity feedback from muscle force and force rate. Our simulations revealed that, in the presence of aberrant musculoskeletal geometries, altered muscle-tendon properties rather than reduced neuromuscular control complexity and spasticity were the primary cause of the crouch gait pattern observed for this child, which is in agreement with the clinical examination. These results suggest that muscle-tendon properties should be the primary target of interventions aiming to restore a more upright gait pattern for this child. This suggestion is in line with the gait analysis following muscle-tendon property and bone deformity corrections. The ability of our simulations to distinguish the contribution of different impairments on walking performance opens the door for identifying targeted treatment strategies with the aim of designing optimized interventions for neuro-musculoskeletal disorders.
Two faces of perceptual awareness during the attentional blink: Gradual and discrete
Authors: Karabay Aytaç , Wilhelm Sophia A. , de Jong Joost , Wang Jing , Martens Sander , Akyürek Elkan G. 
Published: September 2019

AbstractIn a series of experiments, the nature of perceptual awareness during the attentional blink was investigated. Previous work has considered the attentional blink as a discrete, all-or-none phenomenon, indicative of general access to conscious awareness. Using continuous report measures in combination with mixture modeling, the outcomes showed that perceptual awareness during the attentional blink can be a gradual phenomenon. Awareness was not exclusively discrete, but also exhibited a gradual characteristic whenever the spatial extent of attention induced by the first target spanned more than a single location. Under these circumstances, mental representations of blinked targets were impoverished, but did approach the actual identities of the targets. Conversely, when the focus of attention covered only a single location, there was no evidence for any partial knowledge of blinked targets. These two different faces of awareness during the attentional blink challenge current theories of both awareness and temporal attention, which cannot explain the existence of gradual awareness of targets during the attentional blink. To account for the current outcomes, an adaptive gating model is proposed that casts awareness on a continuum between gradual and discrete, rather than as being of either single kind.
The B. subtilis Rok protein compacts and organizes DNA by bridging
Authors: Qin L. , Erkelens A.M. , Markus D. , Dame R.T. 
Published: September 2019

AbstractRok from Bacillus subtilis is an abundant DNA binding protein similar in function to H-NS-like proteins found in many proteobacteria. Rok binds across the genome with a preference for A/T rich DNA. Such DNA often contains genes of foreign origin that are silenced due to Rok binding. Rok also has been implied in global organization of the B. subtilis genome. However, how Rok binds to DNA and how it represses transcription is unclear. Also, it is unknown whether Rok-mediated gene repression can be induced or relieved following changes in physico-chemical conditions, as noted for H-NS-like proteins. Here we investigate the DNA binding properties of Rok and determine the effects of physico-chemical conditions on these properties. We demonstrate that Rok is a DNA bridging protein similar to H-NS like proteins from E. coli (H-NS), Pseudomonas sp. (MvaT) and Mycobacteria (Lsr2). Strikingly, unlike these proteins, the ability of Rok to bridge DNA is not affected by changes in physico-chemical conditions. Not being a direct sensor of such changes sets Rok apart from other H-NS like proteins. It implies the existence of other (protein-mediated) mechanisms to relieve Rok-mediated gene silencing in response to changes in environmental conditions.
Polypyrimidine Tract Binding Proteins are essential for B cell development
Authors: Monzón-Casanova Elisa , Matheson Louise S. , Tabbada Kristina , Zarnack Kathi , Smith Christopher W. J. , Turner Martin 
Published: September 2019

AbstractPolypyrimidine Tract Binding Protein 1 (PTBP1) is a RNA-binding protein (RBP) expressed throughout B cell development. Deletion of Ptbp1 in mouse pro-B cells results in upregulation of PTBP2 and normal B cell development. We show that PTBP2 compensates for PTBP1 in B cell ontogeny as deletion of both Ptbp1 and Ptbp2 results in a complete block at the pro-B cell stage and a lack of mature B cells. In pro-B cells PTBP1 ensures precise synchronisation of the activity of cyclin dependent kinases at distinct stages of the cell cycle, suppresses S-phase entry and promotes progression into mitosis. PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CYCLIN-D2, c-MYC, p107 and CDC25B. Our results reveal a previously unrecognised mechanism mediated by a RBP that is essential for B cell ontogeny and integrates transcriptional and post-translational determinants of progression through the cell cycle.