bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically diverse uropathogenicEscherichia coliadopt a common transcriptional program in patients with urinary tract infections
Authors: Sintsova Anna , Frick-Cheng Arwen , Smith Sara , Pirani Ali , Subashchandrabose Sargurunathan , Snitkin Evan , Mobley Harry L. T. 
Published: April 2019

AbstractUropathogenicEscherichia coli(UPEC) is the major causative agent of uncomplicated urinary tract infections (UTIs). A common virulence genotype of UPEC strains responsible for UTIs is yet to be defined, due to the large variation of virulence factors observed in UPEC strains. We hypothesized that studying UPEC functional responses in patients might reveal universal UPEC features that enable pathogenesis. Here we identify a transcriptional program shared by genetically diverse UPEC strains isolated from 14 patients during uncomplicated UTIs. Strikingly, thisin vivogene expression program is marked by upregulation of translational machinery, providing a mechanism for the rapid growth within the host. Our analysis indicates that switching to a more specialized catabolism and scavenging lifestyle in the host allows for the increased translational output. Our study identifies a common transcriptional program underlying UTIs and illuminates the molecular underpinnings that likely facilitate the fast growth rate of UPEC in infected patients.
CDK2 kinase activity is a regulator of male germ cell fate
Authors: Singh Priti , Patel Ravi K. , Palmer Nathan , Grenier Jennifer K. , Paduch Darius , Kaldis Philipp , Grimson Andrew , Schimenti John C. 
Published: April 2019

ABSTRACTThe ability of men to remain fertile throughout their lives depends upon establishment of a spermatogonial stem cell (SSC) pool from gonocyte progenitors, and also maintaining the proper balance between SSC renewal and spermatogenic differentiation throughout life. Depletion of SSCs causes infertility with a Sertoli Cell Only Syndrome (SCOS) phenotype. We previously created a mouse strain in which an inhibitory phosphorylation site (Tyr15) of Cyclin-dependent kinase 2 (Cdk2) was altered. Juvenile males homozygous for this allele (Cdk2Y15S) initiate the first round of spermatogenesis, which originates from prospermatogonia, but meiocytes arrest due to chromosomal defects resembling those inCdk2-/-mice. Subsequent waves of spermatogonial differentiation and meiosis were largely absent, leading to an SCOS-like phenotype. Here, we demonstrate thatCdk2Y15S/Y15Smice possess mitotically active GFRa1+SSC-like cells, but they are impaired in their ability to differentiate. Marker analysis and single cell RNA-seq revealed defective differentiation of gonocytes into SSCs. Biochemical and genetic data demonstrated thatCdk2Y15Sis a gain-of-function allele causing deregulated kinase activity, and its phenotypic effects could be reversed by mutating the Thr160 positive regulatory site incis. These results demonstrate that precise temporal regulation of CDK2 activity in male germ cell development and in the cell cycle is critical for long-term spermatogenic homeostasis.
A role for Hypoxia Inducible Factor 1a (HIF1a) in intermittent hypoxia-dependent changes to spatial memory and synaptic plasticity
Authors: Arias-Cavieres Alejandra , Khuu Maggie A. , Nwakudu Chinwendu U , Barnard Jasmine E. , Dalgin Gokhan , Garcia Alfredo J. 
Published: April 2019

AbstractIntermittent hypoxia (IH), a key feature of sleep apnea, increases the oxygen regulated transcription factor Hypoxia Inducible Factor 1a (HIF1a). Although recognized for its role in IH-dependent changes in cardio-respiratory physiology, it remains unclear how IH-dependent HIF1a signaling affects neurophysiology underlying learning and memory. This study examines how IH affects hippocampal associated learning and memory in wildtype mice and mice heterozygous for the HIF1a gene (HIF1a+/-). In wild-type mice, ten days of IH impaired performance in the Barnes maze increased hippocampal HIF1a and elevated protein carbonyls. These behavioral and biochemical effects of IH were accompanied by a decrease in the N-Methyl-D-Aspartate receptor (NMDAr) and an attenuation of long-term potentiation (LTP) in area CA1. In HIF1a+/-, IH did not impair Barnes maze performance, increase hippocampal HIF1a, or enhance protein carbonyl content. At the network level, IH neither led to a decrease in NMDAr nor impaired LTP. Concurrent antioxidant treatment during IH mitigated the IH-dependent effects on the Barnes maze performance and LTP in wildtype mice. Our findings indicate that IH-dependent HIF1a signaling leads to oxidative stress and reduces NMDAr to impair LTP in area CA1, which contributes to IH-dependent deficits in learning and memory associated with the hippocampus.SignificanceIntermittent Hypoxia is a hallmark of sleep apnea and decreases the threshold for cognitive deficit. We demonstrate that intermittent hypoxia-dependent HIF1a signaling contributes to impairments in hippocampal associated memory. This is co-incidental with HIF1a-mediated alternations in synaptic physiology and increased oxidative stress.Key pointsIntermittent hypoxia (IH) is a hallmark of sleep apnea and is known to cause learning and memory deficits.Hypoxia Inducible Factor 1a (HIF1a), is associated with IH-dependent changes in physiology.IH exposure causes increased hippocampal HIF1a in wild type mice and is associated with elevated oxidative stress, impairments to spatial memory, and suppression of long term potentiation (LTP).IH-dependent suppression of LTP is co-incidental with diminished NMDA receptor contribution to glutamatergic transmission.Following IH, mice heterozygous for HIF1a (HIF1a+/-) do not show an increase in HIF1a and oxidative stress, or changes in either behavior or glutamatergic transmission.
Combined effects of age and BMI are related to altered cortical thickness in adolescence and adulthood
Authors: Westwater Margaret L. , Vilar-López Raquel , Ziauddeen Hisham , Verdejo-García Antonio , Fletcher Paul C. 
Published: April 2019

AbstractOverweight and obesity are associated with functional and structural alterations in the brain, but how these associations change across critical developmental periods remains unknown. Here, we examined the relationship between age, body mass index (BMI) and cortical thickness (CT) in healthy adolescents (n=70; 14 – 19 y) and adults (n=75; 25 – 45 y). We also examined the relationship between adiposity, impulsivity, measured by delay discounting (DD), and CT of the inferior frontal gyrus (IFG), a region key to impulse control. A significant age-by-BMI interaction was observed in both adolescents and adults; however, the direction of this relationship differed between age groups. In adolescents, increased age-adjusted BMI Z-score attenuated age-related thinning globally and in the right superior frontal gyrus. In adults, increased BMI augmented age-related CT reductions, both globally and in bilateral parietal cortex. Although DD was unrelated to adiposity in both groups, increased DD and BMI were both associated with reduced IFG thickness in adults. Our findings suggest that the known age-related changes in CT in adolescence and adulthood are altered by adiposity. The impact of weight on cortical development and its functional implications would suggest that future studies of adolescent and adult brain development take adiposity into account.
Nasal and gut microbiota for sows of different health status within six commercial swine farms from one swine production system
Authors: Arruda Andréia Gonçalves , Deblais Loic , Hale Vanessa , Pairis-Garcia Monique , Srivastava Vishal , Kathayat Dipak , Kumar Anand , Rajashekara Gireesh 
Published: April 2019

AbstractSow culling is an essential practice in swine herds to optimize animal health and productivity; and cull sows represent a considerable proportion of the herd at any given time point. Even though recent studies have reported that the microbiome is associated with susceptibility to diseases, the microbiome in the cull sow population has not been explored. The main objective of this study was to investigate whether there were differences in abundance and diversity of microbes encountered in the gut and upper respiratory tract of sows of different health status (healthy, cull, and compromised cull sows) and different farms. Farms were visited once, 30 individual fecal and nasal swab samples were obtained per farm; and pooled across animals by health status and farm in pools of five. Genomic DNA was extracted and samples were subjected to MiSeq 16S rRNA sequencing using Illumina MiSeq. Diversity analyses were conducted using QIIME. Alpha diversity was analyzed using observed OTUs, PD Whole Tree, and Chao1; and beta diversity was assessed using weighted UniFrac. The mean number of OTUs was 3,846.97±9,078.87 and 28,747.92±14,090.50 for nasal and fecal pooled samples, respectively. Diversity of the nasal microbiota was low compared to the gut microbiota. For nasal samples, there was a difference in diversity between samples from farms 1-6 using the Chao1 metric (p = 0.0005); and weighted beta diversity values indicated clustering by health status. For fecal samples, there was no difference in diversity between compromised, cull, and healthy sows; or between samples from farms 1-6. Weighted PCoA analyses showed an influence of farm of origin on the diversity of pooled fecal samples. Finally, differences at the genus level were found in the fecal microbiota composition of sows of different health status and farm of origin; but not for nasal microbiota.
The anatomical boundary of the rat claustrum
Authors: Dillingham Christopher M , Mathiasen Mathias L , Frost Bethany E , Lambert Marie AC , Bubb Emma J , Jankowski Maciej M , Aggleton John P , O’Mara Shane M 
Published: April 2019

AbstractThe claustrum is a subcortical nucleus that exhibits dense connectivity across the neocortex. Considerable recent progress has been made in establishing its genetic and anatomical characteristics, however a core, contentious issue that regularly presents in the literature pertains to the rostral extent of its anatomical boundary. The present study addressed this issue in the rat brain.Using a combination of immunohistochemistry and neuronal tract tracing, we have examined the expression profiles of several genes that have previously been identified as exhibiting a differential expression profile in the claustrum relative to the surrounding cortex. The expression profiles of parvalbumin, crystallin mu (Crym), and guanine nucleotide binding protein (G protein), gamma 2 (Gng2) were assessed immunohistochemically alongside, or in combination with cortical anterograde, or retrograde tracer injections. Retrograde neuronal tracer injections into various thalamic nuclei were used to further establish the rostral border of the claustrum.Expression of all three markers delineated a nuclear boundary that extended considerably (~500 μm) beyond the anterior horn of the neostriatum. Cortical retrograde and anterograde neuronal tracer injections, respectively, revealed distributions of cortically-projecting claustral neurons and cortical efferent inputs to the claustrum that overlapped with the gene marker-derived claustrum boundary. Finally, retrograde tracer injections centred in nucleus reuniens, whilst including the rhomboid, mediodorsal and centromedial nuclei, revealed that insular cortico-thalamic projections encapsulated a claustral area, with strongly diminished cell label, that corresponded to the claustrum.
Spherical Spindle Shape Promotes Perpendicular Cortical Orientation by Preventing Isometric Cortical Pulling on both Spindle Poles during C. elegans Female Meiosis
Authors: Vargas Elizabeth , McNally Karen P. , Cortes Daniel B. , Panzica Michelle T. , Shaub-Maddox Amy , McNally Francis J. 
Published: April 2019

AbstractMeiotic spindles are positioned perpendicular to the oocyte cortex to facilitate segregation of chromosomes into a large egg and a tiny polar body. In C. elegans, spindles are initially ellipsoid and parallel to the cortex before shortening to a spherical shape and rotating to the perpendicular orientation by dynein-driven cortical pulling. The mechanistic connection between spindle shape and rotation has remained elusive. Here we used mutants of the microtubule-severing protein katanin to manipulate spindle shape without eliminating cortical pulling. In a katanin mutant, spindles remained ellipsoid, had pointed poles and became trapped in either a diagonal or a parallel orientation. Results indicated that astral microtubules emanating from both spindle poles initially engage in cortical pulling until microtubules emanating from one pole detach from the cortex allowing pivoting of the spindle. The lower viscous drag experienced by spherical spindles prevented recapture of the cortex by astral microtubules emanating from the detached pole. In addition, maximizing contact between pole dynein and cortical dynein stabilizes round poles in a perpendicular orientation. Spherical spindle shape can thus promote perpendicular orientation by two distinct mechanisms.
Conserved architecture of Tc toxins from human and insect pathogenic bacteria
Authors: Leidreiter Franziska , Roderer Daniel , Meusch Dominic , Gatsogiannis Christos , Benz Roland , Raunser Stefan 
Published: April 2019

AbstractTc toxin complexes use a syringe-like mechanism to penetrate the membrane and translocate a toxic enzyme into the host cytosol. They are composed of three components: TcA, TcB and TcC. Until recently, low-resolution structures of TcA from different bacteria suggested that Tc toxins differ considerably in their architecture and possibly in their mechanism of action. Here, we present high-resolution structures and functional studies of five TcAs from different insect and human pathogenic bacteria. Contrary to previous expectations, their overall composition and domain organization is almost identical. The TcAs assemble as a pentamer with a central α-helical channel surrounded by a shell composed of conserved α-helical domains and variable β-sheet domains. Essential structural features, including a conserved trefoil protein knot, are present in all five TcAs, suggesting a common mechanism of action. All TcAs form functional pores and can be combined with TcB-TcC subunits from other species resulting in chimeric holotoxins. We have identified a conserved ionic pair that stabilizes the shell, likely operating as a strong latch that only springs open after the destabilization of other regions. Our results lead to new insights into the architecture and host specificity of the Tc toxin family.
Tissue and cell-type specific expression of a splice variant in the II-III cytoplasmic loop ofCacna1b
Authors: Alexandra Bunda , Brianna LaCarubba , Marie Akiki , Arturo Andrade 
Published: April 2019

ABSTRACTPresynaptic CaV2.2 (N-type) channels are fundamental for transmitter release across the nervous system. The gene encoding CaV2.2 channels,Cacna1b, contains alternatively spliced exons that originate functionally distinct splice variants (e18a, e24a, e31a and 37a/37b). Alternative splicing of the cassette exon 18a generates two mRNA transcripts (+e18a-Cacna1band Δe18a-Cacna1b). In this study, using novel mouse genetic models and in situ hybridization (BaseScope™), we confirmed that +e18a-Cacna1bsplice variants are expressed in monoaminergic regions of midbrain. We expanded these studies and identified +e18a-Cacna1bmRNA in deep cerebellar cells and spinal cord motor neurons. Furthermore, we determined that +e18a-Cacna1bis enriched in cholecystokinin expressing interneurons. Our results provide key information to understand cell-specific functions of CaV2.2 channels.
Insights from Fisher’s geometric model on the likelihood of speciation under different histories of environmental change
Authors: Yamaguchi Ryo , Otto Sarah P. 
Published: April 2019

AbstractThe formation of new species via the accumulation of incompatible genetic changes is thought to result either from ecologically-based divergent natural selection or the order by which mutations happen to arise, leading to different evolutionary trajectories even under similar selection pressures. There is growing evidence in support of both ecological speciation and mutation-order speciation, but how different environmental scenarios affect the rate of species formation remains underexplored. We use a simple model of optimizing selection on multiple traits (“Fisher’s geometric model”) to determine the conditions that generate genetic incompatibilities in a changing environment. We find that incompatibilities are likely to accumulate in isolated populations adapting to different environments, consistent with ecological speciation. Incompatibilities also arise when isolated populations face a similar novel environment; these cases of mutation-order speciation are particularly likely when the environment changes rapidly and favors the accumulation of large-effect mutations. In addition, we find that homoploid hybrid speciation is likely to occur either when new environments arise in between the parental environments or when parental populations have accumulated large-effect mutations following a period of rapid adaptation. Our results indicate that periods of rapid environmental change are particularly conducive to speciation, especially mutation-order or hybrid speciation.
A discrete fireworks optimization algorithm to optimize multi-matching selective assembly problem with non-normal dimensional distribution
Authors: Liu Zhenyu , Nan Zhang , Qiu Chan , Tan Jianrong , Zhou Jingsong , Yao Yao 
Published: April 2019

Purpose
The purpose of this paper is to apply firework optimization algorithm to optimize multi-matching selective assembly problem with non-normal dimensional distribution.

Design/methodology/approach
In this paper, a multi-matching selective assembly approach based on discrete fireworks optimization (DFWO) algorithm is proposed to find the optimal combination of mating parts. The approach introduces new operator with the way of 3-opt and also uses a stochastic selection strategy, combines the discrete selective assembly problem with firework optimization algorithm properly and finds the best combination scheme of mating parts with non-normal dimensional distributions through powerful global search capability of the firework optimization algorithm.

Findings
The effects of different control parameters, including the number of initial fireworks and the coefficient controlling the total number of sparks generated by the fireworks on the evolution performance, are discussed, and a promising higher performance of the proposed selective assembly approach is verified through comparison with other selective assembly methods.

Practical implications
The best combination of mating parts is realized through the proposed selective assembly approach, and workers can select suitable mating parts under the guidance of the combination to increase the assembly efficiency and reduce the amount of surplus parts.

Originality/value
A DFWO algorithm is first designed to combine with multi-matching selective assembly method. For the case of an assembly product, the specific mapping rule and key technologies of DFWO algorithm are proposed.
An RFID and sensor technology-based warehouse center: assessment of new model on a superstore in China
Authors: Liu Hao , Yao Zhong , Zeng Li , Luan Jing 
Published: April 2019

PurposeLarge supermarkets, chain stores and enterprises with large-scale warehousing put forward higher standards and requirements for the automation and informatization of warehouses. As one of the fast-growing commercial supermarkets in China, the traditional warehouse management mode has restricted the rapid development of Yonghui Superstores to a certain extent. The purpose of this paper is to find out how the existing warehouse mode can be changed and to solve the existing problems of warehouse management of Yonghui Superstores.Design/methodology/approachThis research puts forward construction of warehouse center, which is based on radio frequency identification (RFID) and sensor technology, then designs the model for receiving, storage, operations management, distribution and outbound to solve the existing problems of warehouse management of Yonghui Superstores.FindingsWhat technologies should be adopted to meet storage requirements? How to monitor the storage environment in real time and improve the operation and management level of the warehouse? This study found that building a warehouse center based on RFID and sensor technology was a good solution.Research limitations/implicationsThe Yonghui Superstores warehouse center model lacks corresponding simulation experiments, and the investment and income are difficult to estimate quantitatively.Practical implicationsThis paper has designed and discussed the warehouse center model based on RFID and sensor technology, which provides a few references for the actual investment and construction of a warehouse center. In addition, the warehouse center model has strong generalized applicability and could be widely used in various enterprises.Social implicationsThe warehouse center could improve the warehouse management level of Yonghui Superstores and change the traditional warehouse management mode. To some extent, it improves the enterprise flexibility of the market, which will be of great significance to improve business efficiency and enhance brand image and competitiveness.Originality/valueThis study takes Yonghui Superstores as a case to analyze the problems of warehousing management in detail and then designs a warehouse center based on RFID and sensor technology. The study discusses the location and distribution, software and hardware selection, benefits evaluation, significances and return on investment, which makes the warehouse center model versatile, technically feasible and economically applicable.
How prevalent is mental ill-health in the workplace – and how can employers help workers who are suffering?
Authors: Sikafi Zain 
Published: April 2019

Purpose
This research was commissioned by Mynurva in October 2018. The independent, nationally representative survey was conducted among more than 2,000 UK adults to uncover the number of full-time workers who suffer from mental health problems, how many of them seek help for their issues, and the main barriers that hold them back from doing so.

Design/methodology/approach
A nationally representative sample of 2,003 adults in employment were surveyed about their mental health. Via an online survey, employees responding that they had experienced mental health problems were asked to respond further to a series of statements. Contingency tables were then produced, revealing what percentage of respondents agreed or disagreed with each statement that was presented to them.

Findings
Almost a third (32 per cent) of full-time employees have suffered from mental health problems in the workplace. More than one in three workers suffering from mental health symptoms have never sought any professional help, and at 42 per cent, male workers were more likely than female workers (32 per cent) not to seek help. In total, 44 per cent have never disclosed their issues to a manager at work. Of those struggling with their mental health, the authors found that 55 per cent of workers fear admitting their problems to a manager would hinder their chances of a promotion. A majority (59 per cent) also believe that if their mental health problems became common knowledge in the office, then it would negatively affect their relationships with colleagues. This figure rises to 71 per cent among workers of age 18-34. Confidentiality was cited as a key obstacle for employees, with 58 per cent worrying that their mental health problems would not remain confidential if they were to discuss them in the workplace. There was a significant rise among millennials, 68 per cent of which shared these sentiments.

Originality/value
The authors commissioned Opinium to conduct independent research in the UK.