bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Vitamin D Supplementation on 25(OH)D Status in Elite Athletes With Spinal Cord Injury
Authors: Pritchett Kelly , Pritchett Robert C. , Stark Lauren , Broad Elizabeth , LaCroix Melissa 
Published: May 2018

Recent studies suggest that a substantial proportion of athletes with spinal cord injury have insufficient 25(OH) vitamin D (25(OH)D) status, which may be associated with decreased muscle strength. This study consisted of two parts: (a) to examine the effects of a 12- to 16-week vitamin D3 supplementation protocol on 25(OH)D concentration and (b) to determine whether subsequent 25(OH)D status impacts muscle performance in elite athletes with spinal cord injury. Thirty-four members (age: 33 ± 15 years, weight: 69.6 ± 28.2 kg, and height: 170.2 ± 25.4 cm) of the U.S. and Canadian Paralympic program participated in the study. 25(OH)D concentrations and performance measures (handgrip strength and 20-m wheelchair sprint) were assessed pre- and postsupplementation. Participants were assigned a vitamin D3 supplementation protocol based on initial 25(OH)D concentrations. Participants with deficient 25(OH)D status (<50 nmol/L) received 50,000 IU/week for 8 weeks, and participants with insufficient status (50–75 nmol/L) received 35,000 IU/week for 4 weeks, after which both received a maintenance dose of 15,000 IU/week. Participants with sufficient status (>75 nmol/L) received the maintenance dose of 15,000 IU/week. 25(OH)D concentrations increased significantly (p < .001; 66.3 ± 24.3 nmol/L and 111.3 ± 30.8 nmol/L pre- and postsupplementation, respectively). About 26% of athletes had sufficient 25(OH)D concentrations presupplementation, and 91% had sufficient concentrations postsupplementation. About 62% of participants improved handgrip strength postsupplementation with no change in 20-m wheelchair sprint performance. The supplementation protocol was effective for achieving sufficient vitamin D concentrations in elite athletes with spinal cord injury.
Longitudinal Changes in Body Composition Assessed Using DXA and Surface Anthropometry Show Good Agreement in Elite Rugby Union Athletes
Authors: Zemski Adam J. , Keating Shelley E. , Broad Elizabeth M. , Slater Gary J. 
Published: May 2018

Rugby union athletes have divergent body composition based on the demands of their on-field playing position and ethnicity. With an established association between physique traits and positional requirements, body composition assessment is routinely undertaken. Surface anthropometry and dual-energy X-ray absorptiometry (DXA) are the most common assessment techniques used, often undertaken synchronously. This study aims to investigate the association between DXA and surface anthropometry when assessing longitudinal changes in fat-free mass (FFM) and fat mass (FM) in rugby union athletes. Thirty-nine elite male rugby union athletes (age: 25.7 ± 3.1 years, stature: 187.6 ± 7.7 cm, and mass: 104.1 ± 12.2 kg) underwent assessment via DXA and surface anthropometry multiple times over three consecutive international seasons. Changes in the lean mass index, an empirical measure to assess proportional variation in FFM, showed large agreement with changes in DXA FFM (r = .54, standard error of the estimate = 1.5%, p < .001); the strength of association was stronger among forwards (r = .63) compared with backs (r = .38). Changes in the sum of seven skinfolds showed very large agreement with changes in DXA FM (r = .73, standard error of the estimate = 5.8%, p < .001), with meaningful differences observed regardless of ethnicity (Whites: r = .75 and Polynesians: r = .62). The lean mass index and sum of seven skinfolds were able to predict the direction of change in FFM and FM 86% and 91% of the time, respectively, when DXA change was >1 kg. Surface anthropometry measures provide a robust indication of the direction of change in FFM and FM, although caution may need to be applied when interpreting magnitude of change, particularly with FM.
Whey Protein Augments Leucinemia and Postexercise p70S6K1 Activity Compared With a Hydrolyzed Collagen Blend When in Recovery From Training With Low Carbohydrate Availability
Authors: Impey Samuel G. , Hammond Kelly M. , Naughton Robert , Langan-Evans Carl , Shepherd Sam O. , Sharples Adam P. , Cegielski Jessica , Smith Kenneth , Jeromson Stewart , Hamilton David L. , Close Graeme L. , Morton James P. 
Published: May 2018

We examined the effects of whey versus collagen protein on skeletal muscle cell signaling responses associated with mitochondrial biogenesis and protein synthesis in recovery from an acute training session completed with low carbohydrate availability. In a repeated-measures design (after adhering to a 36-hr exercise–dietary intervention to standardize preexercise muscle glycogen), eight males completed a 75-min nonexhaustive cycling protocol and consumed 22 g of a hydrolyzed collagen blend (COLLAGEN) or whey (WHEY) protein 45 min prior to exercise, 22 g during exercise, and 22 g immediately postexercise. Exercise decreased (p < .05) muscle glycogen content by comparable levels from pre- to postexercise in both trials (≈300–150 mmol/kg·dry weight). WHEY protein induced greater increases in plasma branched chain amino acids (p = .03) and leucine (p = .02) than COLLAGEN. Exercise induced (p < .05) similar increases in PGC-1α (fivefold) mRNA at 1.5 hr postexercise between conditions, although no effect of exercise (p > .05) was observed for p53, Parkin, and Beclin1 mRNA. Exercise suppressed (p < .05) p70S6K1 activity in both conditions immediately postexercise (≈25 fmol·min−1·mg−1). Postexercise feeding increased p70S6K1 activity at 1.5 hr postexercise (p < .05), the magnitude of which was greater (p < .05) in WHEY (180 ± 105 fmol·min−1·mg−1) versus COLLAGEN (73 ± 42 fmol·min−1·mg−1). We conclude that protein composition does not modulate markers of mitochondrial biogenesis when in recovery from a training session deliberately completed with low carbohydrate availability. By contrast, whey protein augments postexercise p70S6K activity compared with hydrolyzed collagen, as likely mediated via increased leucine availability.
Preseason Body Composition Adaptations in Elite White and Polynesian Rugby Union Athletes
Authors: Zemski Adam J. , Keating Shelley E. , Broad Elizabeth M. , Marsh Damian J. , Hind Karen , Slater Gary J. 
Published: May 2018

During preseason training, rugby union (RU) athletes endeavor to enhance physical performance characteristics that are aligned with on-field success. Specific physique traits are associated with performance; therefore body composition assessment is routinely undertaken in elite environments. This study aimed to quantify preseason physique changes in elite RU athletes with unique morphology and divergent ethnicity. Twenty-two White and Polynesian professional RU athletes received dual-energy X-ray absorptiometry assessments at the beginning and conclusion of an 11-week preseason. Interactions between on-field playing position and ethnicity in body composition adaptations were explored, and the least significant change model was used to evaluate variations at the individual level. There were no combined interaction effects with the variables position and ethnicity and any body composition measure. After accounting for baseline body composition, Whites gained more lean mass during the preseason than Polynesians (2,425 ± 1,303 g vs. 1,115 ± 1,169 g; F = 5.4, p = .03). Significant main effects of time were found for whole body and all regional measures with fat mass decreasing (F = 31.1–52.0, p < .01), and lean mass increasing (F = 12.0–40.4, p < .01). Seventeen athletes (nine White and eight Polynesian) had a reduction in fat mass, and eight athletes (six White and two Polynesian) increased lean mass. This study describes significant and meaningful physique changes in elite RU athletes during a preseason period. Given the individualized approach applied to athletes in regard to nutrition and conditioning interventions, a similar approach to that used in this study is recommended to assess physique changes in this population.
Evolution of Antibiotic Resistance in Biofilm and Planktonic Pseudomonas aeruginosa Populations Exposed to Subinhibitory Levels of Ciprofloxacin
Authors: Ahmed Marwa N. , Porse Andreas , Sommer Morten Otto Alexander , Høiby Niels , Ciofu Oana 
Published: May 2018

ABSTRACT

The opportunistic Gram-negative pathogen
Pseudomonas aeruginosa
, known for its intrinsic and acquired antibiotic resistance, has a notorious ability to form biofilms, which often facilitate chronic infections. The evolutionary paths to antibiotic resistance have mainly been investigated in planktonic cultures and are less studied in biofilms. We experimentally evolved
P. aeruginosa
PAO1 colony biofilms and stationary-phase planktonic cultures for seven passages in the presence of subinhibitory levels (0.1 mg/liter) of ciprofloxacin (CIP) and performed a genotypic (whole-bacterial population sequencing) and phenotypic assessment of the populations. We observed a higher proportion of CIP resistance in the CIP-evolved biofilm populations than in planktonic populations exposed to the same drug concentrations. However, the MICs of ciprofloxacin were lower in CIP-resistant isolates selected from the biofilm population than the MICs of CIP-resistant isolates from the planktonic cultures. We found common evolutionary trajectories between the different lineages, with mutations in known CIP resistance determinants as well as growth condition-dependent adaptations. We observed a general trend toward a reduction in type IV-pilus-dependent motility (twitching) in CIP-evolved populations and a loss of virulence-associated traits in the populations evolved in the absence of antibiotic. In conclusion, our data indicate that biofilms facilitate the development of low-level mutational resistance, probably due to the lower effective drug exposure than in planktonic cultures. These results provide a framework for the selection process of resistant variants and the evolutionary mechanisms involved under the two different growth conditions.
Biological Roles Played by Sphingolipids in Dimorphic and Filamentous Fungi
Authors: Fernandes Caroline Mota , Goldman Gustavo H. , Del Poeta Maurizio 
Published: May 2018

ABSTRACTFilamentous and dimorphic fungi cause invasive mycoses associated with high mortality rates. Among the fungal determinants involved in the establishment of infection, glycosphingolipids (GSLs) have gained increased interest in the last few decades. GSLs are ubiquitous membrane components that have been isolated from both filamentous and dimorphic species and play a crucial role in polarized growth as well as hypha-to-yeast transition. In fungi, two major classes of GSLs are found: neutral and acidic GSLs. Neutral GSLs comprise glucosylceramide and galactosylceramide, which utilize Δ4-Δ8-9-methyl-sphingadienine as a sphingoid base, linked to a C16–18fatty acid chain, forming ceramide, and to a sugar residue, such as glucose or galactose. In contrast, acidic GSLs include glycosylinositol phosphorylceramides (GIPCs), composed of phytosphingosine attached to a long or very long fatty acid chain (C18–26) and to diverse and complex glycan groups via an inositol-phosphate linker. GIPCs are absent in mammalian cells, while fungal glucosylceramide and galactosylceramide are present but diverge structurally from their counterparts. Therefore, these compounds and their biosynthetic pathways represent potential targets for the development of selective therapeutic strategies. In this minireview, we discuss the enzymatic steps involved in the production of fungal GSLs, analyze their structure, and address the role of the currently characterized genes in the biology and pathogenesis of filamentous and dimorphic fungi.
Toward an Improved Meningococcal Serogroup B Assay
Authors: Poolman Jan 
Published: May 2018

ABSTRACT

Because of diverse sequences and differential expression of surface structures on individual invasive
Neisseria meningitidis
serogroup B (MenB) strains, predicting the efficacy of MenB vaccines using traditional human serum bactericidal assays (hSBA) is impractical. The meningococcal antigen surface expression (MEASURE) assay uses flow cytometry to quantitate the expression of factor H binding proteins (fHbp) contained in the bivalent rLP2086 MenB vaccine. To date, experience with MEASURE has been lacking, and in a long-awaited article, McNeil et al. (mBio 9:e00036-18,
https://doi.org/10.1128/mBio.00036-18
), provide detailed mapping of a cross-reactive antibody binding epitope and explore the potential utility of MEASURE in predicting the susceptibility of individual MenB strains to antibody-mediated killing. Remaining questions center around why some strains with high fHbp expression are nonsusceptible to anti-fHbp antibody killing. Consideration of alternative methods, such as a standardized enzyme-linked immunosorbent assay (ELISA), might offer a more readily available and reproducible assay for wider use.
CagY-Dependent Regulation of Type IV Secretion in Helicobacter pylori Is Associated with Alterations in Integrin Binding
Authors: Skoog Emma C. , Morikis Vasilios A. , Martin Miriam E. , Foster Greg A. , Cai Lucy P. , Hansen Lori M. , Li Beibei , Gaddy Jennifer A. , Simon Scott I. , Solnick Jay V. 
Published: May 2018

ABSTRACT

Strains of
Helicobacter pylori
that cause ulcer or gastric cancer typically express a type IV secretion system (T4SS) encoded by the
cag
pathogenicity island (
cag
PAI). CagY is an ortholog of VirB10 that, unlike other VirB10 orthologs, has a large middle repeat region (MRR) with extensive repetitive sequence motifs, which undergo CD4
+
T cell-dependent recombination during infection of mice. Recombination in the CagY MRR reduces T4SS function, diminishes the host inflammatory response, and enables the bacteria to colonize at a higher density. Since CagY is known to bind human α
5
β
1
integrin, we tested the hypothesis that recombination in the CagY MRR regulates T4SS function by modulating binding to α
5
β
1
integrin. Using a cell-free microfluidic assay, we found that
H. pylori
binding to α
5
β
1
integrin under shear flow is dependent on the CagY MRR, but independent of the presence of the T4SS pili, which are only formed when
H. pylori
is in contact with host cells. Similarly, expression of CagY in the absence of other T4SS genes was necessary and sufficient for whole bacterial cell binding to α
5
β
1
integrin. Bacteria with variant
cagY
alleles that reduced T4SS function showed comparable reduction in binding to α
5
β
1
integrin, although CagY was still expressed on the bacterial surface. We speculate that
cagY-
dependent modulation of
H. pylori
T4SS function is mediated by alterations in binding to α
5
β
1
integrin, which in turn regulates the host inflammatory response so as to maximize persistent infection.

IMPORTANCE
Infection with
H. pylori
can cause peptic ulcers and is the most important risk factor for gastric cancer, the third most common cause of cancer death worldwide. The major
H. pylori
virulence factor that determines whether infection causes disease or asymptomatic colonization is the type IV secretion system (T4SS), a sort of molecular syringe that injects bacterial products into gastric epithelial cells and alters host cell physiology. We previously showed that recombination in CagY, an essential T4SS component, modulates the function of the T4SS. Here we found that these recombination events produce parallel changes in specific binding to α
5
β
1
integrin, a host cell receptor that is essential for T4SS-dependent translocation of bacterial effectors. We propose that CagY-dependent binding to α
5
β
1
integrin acts like a molecular rheostat that alters T4SS function and modulates the host immune response to promote persistent infection.
SAMHD1 Phosphorylation Coordinates the Anti-HIV-1 Response by Diverse Interferons and Tyrosine Kinase Inhibition
Authors: Szaniawski Matthew A. , Spivak Adam M. , Cox James E. , Catrow Jonathan L. , Hanley Timothy , Williams Elizabeth S. C. P. , Tremblay Michel J. , Bosque Alberto , Planelles Vicente 
Published: May 2018

ABSTRACT
Macrophages are susceptible to human immunodeficiency virus type 1 (HIV-1) infection despite abundant expression of antiviral proteins. Perhaps the most important antiviral protein is the restriction factor sterile alpha motif domain and histidine/aspartic acid domain-containing protein 1 (SAMHD1). We investigated the role of SAMHD1 and its phospho-dependent regulation in the context of HIV-1 infection in primary human monocyte-derived macrophages and the ability of various interferons (IFNs) and pharmacologic agents to modulate SAMHD1. Here we show that stimulation by type I, type II, and to a lesser degree, type III interferons share activation of SAMHD1 via dephosphorylation at threonine-592 as a consequence of signaling. Cyclin-dependent kinase 1 (CDK1), a known effector kinase for SAMHD1, was downregulated at the protein level by all IFN types tested. Pharmacologic inhibition or small interfering RNA (siRNA)-mediated knockdown of CDK1 phenocopied the effects of IFN on SAMHD1. A panel of FDA-approved tyrosine kinase inhibitors potently induced activation of SAMHD1 and subsequent HIV-1 inhibition. The viral restriction imposed via IFNs or dasatinib could be overcome through depletion of SAMHD1, indicating that their effects are exerted primarily through this pathway. Our results demonstrate that SAMHD1 activation, but not transcriptional upregulation or protein induction, is the predominant mechanism of HIV-1 restriction induced by type I, type II, and type III IFN signaling in macrophages. Furthermore, SAMHD1 activation presents a pharmacologically actionable target through which HIV-1 infection can be subverted.

IMPORTANCE
Our experimental results demonstrate that SAMHD1 dephosphorylation at threonine-592 represents a central mechanism of HIV-1 restriction that is common to the three known families of IFNs. While IFN types I and II were potent inhibitors of HIV-1, type III IFN showed modest to undetectable activity. Regulation of SAMHD1 by IFNs involved changes in phosphorylation status but not in protein levels. Phosphorylation of SAMHD1 in macrophages occurred at least in part via CDK1. Tyrosine kinase inhibitors similarly induced SAMHD1 dephosphorylation, which protects macrophages from HIV-1 in a SAMHD1-dependent manner. SAMHD1 is a critical restriction factor regulating HIV-1 infection of macrophages.
Underutilisation of public access defibrillation is related to retrieval distance and time-dependent availability
Authors: Deakin Charles D , Anfield Steve , Hodgetts Gillian A 
Published: May 2018

IntroductionPublic access defibrillation doubles the chances of neurologically intact survival following out-of-hospital cardiac arrest (OHCA). Although there are increasing numbers of defibrillators (automated external defibrillator (AEDs)) available in the community, they are used infrequently, despite often being available. We aimed to match OHCAs with known AED locations in order to understand AED availability, the effects of reduced AED availability at night and the operational radius at which they can be effectively retrieved.MethodsAll emergency calls to South Central Ambulance Service from April 2014 to April 2016 were screened to identify cardiac arrests. Each was mapped to the nearest AED, according to the time of day. Mapping software was used to calculate the actual walking distance for a bystander between each OHCA and respective AED, when travelling at a brisk walking speed (4 mph).Results4012 cardiac arrests were identified and mapped to one of 2076 AEDs. All AEDs were available during daytime hours, but only 713 at night (34.3%). 5.91% of cardiac arrests were within a retrieval (walking) radius of 100 m during the day, falling to 1.59% out-of-hours. Distances to rural AEDs were greater than in urban areas (P<0.0001). An AED could potentially have been retrieved prior to actual ambulance arrival in 25.3% cases.ConclusionExisting AEDs are underused; 36.4% of OHCAs are located within 500 m of an AED. Although more AEDs will improve availability, greater use can be made of existing AEDs, particularly by ensuring they are all available on a 24/7 basis.
Novel genomic findings in multiple myeloma identified through routine diagnostic sequencing
Authors: Ryland Georgina L , Jones Kate , Chin Melody , Markham John , Aydogan Elle , Kankanige Yamuna , Caruso Marisa , Guinto Jerick , Dickinson Michael , Prince H Miles , Yong Kwee , Blombery Piers 
Published: May 2018

AimsMultiple myeloma is a genomically complex haematological malignancy with many genomic alterations recognised as important in diagnosis, prognosis and therapeutic decision making. Here, we provide a summary of genomic findings identified through routine diagnostic next-generation sequencing at our centre.MethodsA cohort of 86 patients with multiple myeloma underwent diagnostic sequencing using a custom hybridisation-based panel targeting 104 genes. Sequence variants, genome-wide copy number changes and structural rearrangements were detected using an inhouse-developed bioinformatics pipeline.ResultsAt least one mutation was found in 69 (80%) patients. Frequently mutated genes includedTP53(36%),KRAS(22.1%),NRAS(15.1%),FAM46C/DIS3(8.1%) andTET2/FGFR3(5.8%), including multiple mutations not previously described in myeloma. Importantly we observedTP53mutations in the absence of a 17 p deletion in 8% of the cohort, highlighting the need for sequencing-based assessment in addition to cytogenetics to identify these high-risk patients. Multiple novel copy number changes and immunoglobulin heavy chain translocations are also discussed.ConclusionsOur results demonstrate that many clinically relevant genomic findings remain in multiple myeloma which have not yet been identified through large-scale sequencing efforts, and provide important mechanistic insights into plasma cell pathobiology.
Severity of cerebral vasospasm associated with development of collaterals following aneurysmal subarachnoid hemorrhage
Authors: Al-Mufti Fawaz , Witsch Jens , Manning Nathan , Crimmins Michael , Amuluru Krishna , Agarwal Sachin , Park Soojin , Willey Joshua Z , Kamel Hooman , Connolly E Sander , Meyers Philip M , Claassen Jan 
Published: May 2018

IntroductionCerebral collateral circulation has been studied extensively in ischemic stroke where it has been shown to be a predictor of reperfusion, final infarct size, and outcome. Little is known about the significance of the collaterals in the setting of aneurysmal subarachnoid hemorrhage (aSAH). We sought to evaluate the effect of cerebral vasospasm on the development of cerebral collaterals following aneurysmal subarachnoid hemorrhage and the effects of the latter on delayed cerebral ischemia (DCI).MethodsWe retrospectively evaluated 64 aSAH patients with evidence of DCI between day 5 and 7, enrolled in a prospectively maintained observational cohort study. Angiograms were evaluated by four blinded neurointerventionalists. We compared good collateral grades to poor collateral grades, additionally we compared enrolled individuals with any collaterals versus patients who had no collaterals.ResultsInter-rater reliability for collateral grades was substantial (weighted kappa 0.632). Mild vasospasm was more frequent in patients with poor collateral grades compared with patients with good collateral grades (32% vs 4% P=0.012). There was no difference between the collateral groups with regards to DCI, functional, or cognitive outcome. Patients adjudicated to have any collaterals were more likely to have severe vasospasm (62% vs 33% P=0.023) and less likely to have mild vasospasm (37% vs 9% P=0.007). In a multivariable model, vasospasm severity remained associated with collateral status, while aneurysm location was not.ConclusionsThe severity of vasospasm following aSAH was associated with the development of collaterals. There was no difference between collateral grades with regards to DCI or outcome.