bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose and lactate as metabolic constraints on presynaptic transmission at an excitatory synapse
Authors: Lucas Sarah J. , Michel Christophe B. , Marra Vincenzo , Smalley Joshua L. , Hennig Matthias H. , Graham Bruce P. , Forsythe Ian D. 
Published: February 2018

Key points
Synapses have high energy demands which increase during intense activity. We show that presynaptic terminals can utilise extracellular glucose or lactate to generate energy to maintain synaptic transmission.
Reducing energy substrates induces a metabolic stress: presynaptic ATP depletion impaired synaptic transmission through a reduction in the number of functional synaptic vesicle release sites and a slowing of vesicle pool replenishment, without a consistent change in release probability.
Metabolic function is compromised in many pathological conditions (e.g. stroke, traumatic brain injury and neurodegeneration). Knowledge of how synaptic transmission is constrained by metabolic stress, especially during intense brain activity, will provide insights to improve cognition following pathological insults.
AbstractThe synapse has high energy demands, which increase during intense activity. Presynaptic ATP production depends on substrate availability and usage will increase during activity, which in turn could influence transmitter release and information transmission. We investigated transmitter release at the mouse calyx of Held synapse using glucose or lactate (10, 1 or 0 mm) as the extracellular substrates while inducing metabolic stress. High‐frequency stimulation (HFS) and recovery paradigms evoked trains of EPSCs monitored under voltage‐clamp. Whilst postsynaptic intracellular ATP was stabilised by diffusion from the patch pipette, depletion of glucose increased EPSC depression during HFS and impaired subsequent recovery. Computational modelling of these data demonstrated a reduction in the number of functional release sites and slowed vesicle pool replenishment during metabolic stress, with little change in release probability. Directly depleting presynaptic terminal ATP impaired transmitter release in an analogous manner to glucose depletion. In the absence of glucose, presynaptic terminal metabolism could utilise lactate from the aCSF and this was blocked by inhibition of monocarboxylate transporters (MCTs). MCT inhibitors significantly suppressed transmission in low glucose, implying that lactate is a presynaptic substrate. Additionally, block of glycogenolysis accelerated synaptic transmission failure in the absence of extracellular glucose, consistent with supplemental supply of lactate by local astrocytes. We conclude that both glucose and lactate support presynaptic metabolism and that limited availability, exacerbated by high‐intensity firing, constrains presynaptic ATP, impeding transmission through a reduction in functional presynaptic release sites as vesicle recycling slows when ATP levels are low.
Effect of Exercise Duration on Subsequent Appetite and Energy Intake in Obese Adolescent Girls
Authors: Masurier Julie , Mathieu Marie-Eve , Fearnbach Stephanie Nicole , Cardenoux Charlotte , Julian Valérie , Lambert Céline , Pereira Bruno , Duclos Martine , Boirie Yves , Thivel David 
Published: February 2018

There is a growing interest regarding the effect of exercise on appetite and energy intake in youth. While the role of exercise intensity has been a primary focus of study, the effect of exercise duration on subsequent food intake has not been fully examined in obese adolescents. On three separate mornings in a randomly assigned order, obese adolescent girls (n = 20) aged 12–15 years old were asked to perform a rest session (control, CON) or two cycling sessions for 20 (EX20) or 40 min (EX40) set at their ventilatory threshold. Absolute and relative energy intake were measured from an ad libitum lunch meal 30 min after rest or exercise and appetite feelings assessed using visual analogue scales throughout the day. Hunger, satiety, and prospective food consumption were not significantly different between conditions. Absolute energy intake (kcal) did not differ between conditions, while relative energy intake on EX40 (571 ± 381 kcal) was significantly lower than during CON (702 ± 320 kcal; p < .05) and EX20 (736 ± 457 kcal; p < .05). Fat ingestion (in grams) was significantly lower on CON (7.8 ± 3.2 g) compared with EX20 (10.3 ± 4.6 g; p < .01). Protein intake (in grams) was higher on EX20 (37.0 ± 16.6 g) compared with both CON (29.5 ± 11.7 g; p < .01) and EX40 (33.1 ± 10.9 g; p < .05). However, the percentage of total energy derived from each macronutrient was not different between conditions. Obese adolescent girls do not compensate for an acute bout of exercise set at their ventilatory threshold by increasing energy intake, regardless of the exercise duration.
Enterococcus faecalis
Sex Pheromone cCF10 Enhances Conjugative Plasmid Transfer
In Vivo
Authors: Hirt Helmut , Greenwood-Quaintance Kerryl E. , Karau Melissa J. , Till Lisa M. , Kashyap Purna C. , Patel Robin , Dunny Gary M. 
Published: February 2018

ABSTRACT

Cell-cell communication mediated by peptide pheromones (cCF10 [CF]) is essential for high-frequency plasmid transfer
in vitro
in
Enterococcus faecalis
. To examine the role of pheromone signaling
in vivo
, we established either a CF-producing (CF+) recipient or a recipient producing a biologically inactive variant of CF (CF− recipient) in a germfree mouse model 3 days before donor inoculation and determined transfer frequencies of the pheromone-inducible plasmid pCF10. Plasmid transfer was detected in the upper and middle sections of the intestinal tract 5 h after donor inoculation and was highly efficient in the absence of antibiotic selection. The transconjugant/donor ratio reached a maximum level approaching 1 on day 4 in the upper intestinal tract. Plasmid transfer was significantly lower with the CF− recipient. While rescue of the CF− mating defect by coculture with CF+ recipients is easily accomplished
in vitro
, no extracellular complementation occurred
in vivo
. This suggests that most pheromone signaling in the gut occurs between recipient and donor cells in very close proximity. Plasmid-bearing cells (donors plus transconjugants) steadily increased in the population from 0.1% after donor inoculation to about 10% at the conclusion of the experiments. This suggests a selective advantage of pCF10 carriage distinct from antibiotic resistance or bacteriocin production. Our results demonstrate that pheromone signaling is required for efficient pCF10 transfer
in vivo
. In the absence of CF+ recipients, a low level of transfer to CF− recipients occurred in the gut. This may result from low-level host-mediated induction of the donors in the gastrointestinal (GI) tract, similar to that previously observed in serum.

IMPORTANCE
Horizontal gene transfer is a major factor in the biology of
Enterococcus faecalis
, an important nosocomial pathogen. Previous studies showing efficient conjugative plasmid transfer in the gastrointestinal (GI) tracts of experimental animals did not examine how the enterococcal sex pheromone response impacts the efficiency of transfer. Our study demonstrates for the first time pheromone-enhanced, high-frequency plasmid transfer of
E. faecalis
plasmid pCF10 in a mouse model in the absence of antibiotic or bacteriocin selection. Pheromone production by recipients dramatically increased plasmid transfer in germfree mice colonized initially with recipients, followed by donors. The presence of a coresident community of common gut microbes did not significantly reduce
in vivo
plasmid transfer between enterococcal donors and recipients. In mice colonized with enterococcal recipients, we detected plasmid transfer in the intestinal tract within 5 h of addition of donors, before transconjugants could be cultured from feces. Surprisingly, pCF10 carriage provided a competitive fitness advantage unrelated to antibiotic resistance or bacteriocin production.
Functional Analysis of Mating Type Genes and Transcriptome Analysis during Fruiting Body Development ofBotrytis cinerea
Authors: Rodenburg Sander Y. A. , Terhem Razak B. , Veloso Javier , Stassen Joost H. M. , van Kan Jan A. L. 
Published: February 2018

ABSTRACTBotrytis cinereais a plant-pathogenic fungus producing apothecia as sexual fruiting bodies. To study the function of mating type (MAT) genes, single-gene deletion mutants were generated in both genes of theMAT1-1locus and both genes of theMAT1-2locus. Deletion mutants in twoMATgenes were entirely sterile, while mutants in the other twoMATgenes were able to develop stipes but never formed an apothecial disk. Little was known about the reprogramming of gene expression during apothecium development. We analyzed transcriptomes of sclerotia, three stages of apothecium development (primordia, stipes, and apothecial disks), and ascospores by RNA sequencing. Ten secondary metabolite gene clusters were upregulated at the onset of sexual development and downregulated in ascospores released from apothecia. Notably, more than 3,900 genes were differentially expressed in ascospores compared to mature apothecial disks. Among the genes that were upregulated in ascospores were numerous genes encoding virulence factors, which reveals that ascospores are transcriptionally primed for infection prior to their arrival on a host plant. Strikingly, the massive transcriptional changes at the initiation and completion of the sexual cycle often affected clusters of genes, rather than randomly dispersed genes. Thirty-five clusters of genes were jointly upregulated during the onset of sexual reproduction, while 99 clusters of genes (comprising >900 genes) were jointly downregulated in ascospores. These transcriptional changes coincided with changes in expression of genes encoding enzymes participating in chromatin organization, hinting at the occurrence of massive epigenetic regulation of gene expression during sexual reproduction.IMPORTANCEFungal fruiting bodies are formed by sexual reproduction. We studied the development of fruiting bodies (“apothecia”) of the ubiquitous plant-pathogenic ascomyceteBotrytis cinerea. The role of mating type genes in apothecium development was investigated by targeted mutation. Two genes are essential for the initiation of sexual development; mutants in these genes are sterile. Two other genes were not essential for development of stipes; however, they were essential for stipes to develop a disk and produce sexual ascospores. We examined gene expression profiles during apothecium development, as well as in ascospores sampled from apothecia. We provide the first study ever of the transcriptome of pure ascospores in a filamentous fungus. The expression of numerous genes involved in plant infection was induced in the ascospores, implying that ascospores are developmentally primed for infection before their release from apothecia.
The ColM Family, Polymorphic Toxins Breaching the Bacterial Cell Wall
Authors: Ghequire Maarten G. K. , Buchanan Susan K. , De Mot René 
Published: February 2018

ABSTRACT
Bacteria host an arsenal of antagonism-mediating molecules to combat for ecologic space. Bacteriocins represent a pivotal group of secreted antibacterial peptides and proteins assisting in this fight, mainly eliminating relatives. Colicin M, a model for peptidoglycan-interfering bacteriocins in Gram-negative bacteria, appears to be part of a set of polymorphic toxins equipped with such a catalytic domain (ColM) targeting lipid II. Diversifying recombination has enabled parasitism of different receptors and has also given rise to hybrid bacteriocins in which ColM is associated with another toxin module. Remarkably, ColM toxins have recruited a diverse array of immunity partners, comprising cytoplasmic membrane-associated proteins with different topologies. Together, these findings suggest that different immunity mechanisms have evolved for ColM, in contrast to bacteriocins with nuclease activities.
An Autocrine Proliferation Repressor Regulates
Dictyostelium discoideum
Proliferation and Chemorepulsion Using the G Protein-Coupled Receptor GrlH
Authors: Tang Yu , Wu Yuantai , Herlihy Sarah E. , Brito-Aleman Francisco J. , Ting Jose H. , Janetopoulos Chris , Gomer Richard H. 
Published: February 2018

ABSTRACT

In eukaryotic microbes, little is known about signals that inhibit the proliferation of the cells that secrete the signal, and little is known about signals (chemorepellents) that cause cells to move away from the source of the signal. Autocrine proliferation repressor protein A (AprA) is a protein secreted by the eukaryotic microbe
Dictyostelium discoideum
. AprA is a chemorepellent for and inhibits the proliferation of
D. discoideum
. We previously found that cells sense AprA using G proteins, suggesting the existence of a G protein-coupled AprA receptor. To identify the AprA receptor, we screened mutants lacking putative G protein-coupled receptors. We found that, compared to the wild-type strain, cells lacking putative receptor GrlH (
grlH¯
cells) show rapid proliferation, do not have large numbers of cells moving away from the edges of colonies, are insensitive to AprA-induced proliferation inhibition and chemorepulsion, and have decreased AprA binding. Expression of GrlH in
grlH¯
cells (
grlH¯/grlH

OE

) rescues the phenotypes described above. These data indicate that AprA signaling may be mediated by GrlH in
D. discoideum
.

IMPORTANCE
Little is known about how eukaryotic cells can count themselves and thus regulate the size of a tissue or density of cells. In addition, little is known about how eukaryotic cells can sense a repellant signal and move away from the source of the repellant, for instance, to organize the movement of cells in a developing embryo or to move immune cells out of a tissue. In this study, we found that a eukaryotic microbe uses G protein-coupled receptors to mediate both cell density sensing and chemorepulsion.
Objectively measured physical activity, sedentary behaviour and all-cause mortality in older men: does volume of activity matter more than pattern of accumulation?
Authors: Jefferis Barbara J , Parsons Tessa J , Sartini Claudio , Ash Sarah , Lennon Lucy T , Papacosta Olia , Morris Richard W , Wannamethee S Goya , Lee I-Min , Whincup Peter H 
Published: February 2018

ObjectivesTo understand how device-measured sedentary behaviour and physical activity are related to all-cause mortality in older men, an age group with high levels of inactivity and sedentary behaviour.MethodsProspective population-based cohort study of men recruited from 24 UK General Practices in 1978–1980. In 2010–2012, 3137 surviving men were invited to a follow-up, 1655 (aged 71–92 years) agreed. Nurses measured height and weight, men completed health and demographic questionnaires and wore an ActiGraph GT3x accelerometer. All-cause mortality was collected through National Health Service central registers up to 1 June 2016.ResultsAfter median 5.0 years’ follow-up, 194 deaths occurred in 1181 men without pre-existing cardiovascular disease. For each additional 30 min in sedentary behaviour, or light physical activity (LIPA), or 10 min in moderate to vigorous physical activity (MVPA), HRs for mortality were 1.17 (95% CI 1.10 to 1.25), 0.83 (95% CI 0.77 to 0.90) and 0.90 (95% CI 0.84 to 0.96), respectively. Adjustments for confounders did not meaningfully change estimates. Only LIPA remained significant on mutual adjustment for all intensities. The HR for accumulating 150 min MVPA/week in sporadic minutes (achieved by 66% of men) was 0.59 (95% CI 0.43 to 0.81) and 0.58 (95% CI 0.33 to 1.00) for accumulating 150 min MVPA/week in bouts lasting ≥10 min (achieved by 16% of men). Sedentary breaks were not associated with mortality.ConclusionsIn older men, all activities (of light intensity upwards) were beneficial and accumulation of activity in bouts ≥10 min did not appear important beyond total volume of activity. Findings can inform physical activity guidelines for older adults.
Exploring the lived experience and chronic low back pain beliefs of English-speaking Punjabi and white British people: a qualitative study within the NHS
Authors: Singh Gurpreet , Newton Christopher , O’Sullivan Kieran , Soundy Andrew , Heneghan Nicola R 
Published: February 2018

IntroductionDisabling chronic low back pain (CLBP) is associated with negative beliefs and behaviours, which are influenced by culture, religion and interactions with healthcare practitioners (HCPs). In the UK, HCPs encounter people from different cultures and ethnic backgrounds, with South Asian Indians (including Punjabis) forming the largest ethnic minority group. Better understanding of the beliefs and experiences of ethnic minorities with CLBP might inform effective management.ObjectivesTo explore the CLBP beliefs and experiences of English-speaking Punjabi and white British people living with CLBP, explore how beliefs may influence the lived experience of CLBP and conduct cross-cultural comparisons between the two groups.DesignQualitative study using semistructured interviews set within an interpretive description framework and thematic analysis.SettingA National Health Service hospital physiotherapy department, Leicester, UK.Participants10 CLBP participants (5 English-speaking Punjabi and 5 white British) purposively recruited from physiotherapy waiting lists.ResultsParticipants from both groups held negative biomedical CLBP beliefs such as the ‘spine is weak’, experienced unfulfilling interactions with HCPs commonly due to a perceived lack of support and negative psychosocial dimensions of CLBP with most participants catastrophising about their CLBP. Specific findings to Punjabi participants included (1) disruption to cultural-religious well-being, as well as (2) a perceived lack of understanding and empathy regarding their CLBP from the Punjabi community. In contrast to their white British counterparts, Punjabi participants reported initially using passive coping strategies; however, all participants reported a transition towards active coping strategies.ConclusionCLBP beliefs and experiences, irrespective of ethnicity, were primarily biomedically orientated. However, cross-cultural differences included cultural-religious well-being, the community response to CLBP experienced by Punjabi participants and coping styles. These findings might help inform management of people with CLBP.
Pediatric dog bites: a population-based profile
Authors: Fein Jackson , Bogumil David , Upperman Jeffrey S , Burke Rita V 
Published: February 2018

BackgroundPrevious studies have identified risk factors for dog bites in children, but use data from individual trauma centers, with limited generalizability. This study identifies a population risk profile for pediatric dog bites using the National Trauma Data Bank. We hypothesized that the population at risk was younger boys, that such bites occur at home, are moderately severe, and are on the face or neck.MethodsFor this retrospective cross-sectional study, a sample of 7912 children 17 years old and younger with International Classification of Diseases (ICD)-9 event code E906.0, for dog bites, were identified. Datasets from 2007 to 2014 were used. Data included patient’s gender, age, ICD-9 primary and location E-codes, AIS body region and AIS severity.ResultsMost children were 6–12 years old and female, but a similar number fell into the narrower range of 0–2 years old. Injuries in the younger group frequently occurred at home, on the face and head, and with minor severity. Age of the child predicts the location of incident (P<0.001), the severity of injury (P<0.001) and the body region of the injury (P<0.001). Body region of the injury predicted its severity (P<0.001).DiscussionYounger children are more likely to receive dog bites, and bites incurred are likely of greater severity. Children this young cannot yet be taught how to properly interact with a dog.ConclusionsDog bites are a significant source of morbidity for children. Based on the population risk factors profile generated, this study recommends targeting live dog education towards the parents of young children.
Multiparametric MRI of intracranial aneurysms treated with the Woven EndoBridge (WEB): a case of Faraday’s cage?
Authors: Nawka Marie Teresa , Sedlacik Jan , Frölich Andreas , Bester Maxim , Fiehler Jens , Buhk Jan-Hendrik 
Published: February 2018

ObjectiveTo evaluate multiparametric MRI including non-contrast and contrast-enhanced morphological and angiographic techniques for intracranial aneurysms treated with the single-layer Woven EndoBridge (WEB) embolization system applying simultaneous digital subtraction angiography (DSA) as the reference of standard.Materials and methodsWe retrospectively identified all patients with incidental and acute ruptured intracranial aneurysms treated with a WEB device (WEB SL and WEB SLS) between March 2014 and June 2016 in our neurovascular center with early (within 7 days) postinterventional multiparametric MRI as well as mid-term (5–8 months) follow-up MRI and DSA available. Occlusion rates were recorded both in DSA and MR angiography (MRA). In MRI, signal intensities within the WEB as well as in the occluded dome distal to the WEB, if present, were measured by region-of-interest (ROI) analysis.ResultsTwenty-five patients fulfilled the inclusion criteria. Rates of complete/adequate occlusion at mid-term follow-up were 84% with both MRA and DSA. A strong signal loss within the WEB was observed in all MR sequences at initial and follow-up examinations. ROI analysis did not reveal significant differences in non-contrast (P=0.946) and contrast-enhanced imaging (P=0.377). A T1-hyperintense thrombus in the non-WEB-carrying dome was a frequent observation.ConclusionsSignal intensity measurements in multiparametric MRI suggest that neither contrast-enhanced MRA nor morphological sequences are capable of revealing reliable information on the WEB lumen, presumably due to radio frequency shielding. MRI is therefore not suitable for confirming complete thrombus formation within the WEB.