bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil microclimate changes affect soil fungal communities in a Mediterranean pine forest
Authors: Castaño Carles , Lindahl Björn D. , Alday Josu G. , Hagenbo Andreas , Martínez de Aragón Juan , Parladé Javier , Pera Joan , Bonet José Antonio
Published: May 2018

Soil microclimate is a potentially important regulator of the composition of plant‐associated fungal communities in climates with significant drought periods. Here, we investigated the spatio‐temporal dynamics of soil fungal communities in a Mediterranean Pinus pinaster forest in relation to soil moisture and temperature.

Fungal communities in 336 soil samples collected monthly over 1 year from 28 long‐term experimental plots were assessed by PacBio sequencing of ITS2 amplicons. Total fungal biomass was estimated by analysing ergosterol. Community changes were analysed in the context of functional traits.

Soil fungal biomass was lowest during summer and late winter and highest during autumn, concurrent with a greater relative abundance of mycorrhizal species. Intra‐annual spatio‐temporal changes in community composition correlated significantly with soil moisture and temperature. Mycorrhizal fungi were less affected by summer drought than free‐living fungi. In particular, mycorrhizal species of the short‐distance exploration type increased in relative abundance under dry conditions, whereas species of the long‐distance exploration type were more abundant under wetter conditions.

Our observations demonstrate a potential for compositional and functional shifts in fungal communities in response to changing climatic conditions. Free‐living fungi and mycorrhizal species with extensive mycelia may be negatively affected by increasing drought periods in Mediterranean forest ecosystems.
Pathophysiology and treatment of achalasia in a muscle mechanical perspective
Authors: Gregersen Hans , Lo Kar Man
Published: May 2018

This review provides a biomechanical perspective on the pathophysiology and treatment of achalasia. The esophagus is efficient in transporting ingested material to the stomach in healthy subjects. A fine balance exists between the peristaltic forces generated in the esophageal body (which herein is defined as the preload) and the resistance in the outlet, the esophago‐gastric junction (which is defined as the afterload). Achalasia is a rare esophageal disease that progressively over many years challenges esophageal efficacy. Clinical features and current literature are interpreted using well‐known muscle mechanics models and terms from cardiac mechanophysiology. The preload, afterload, length–tension, and strain softening concepts in particular are useful for understanding the remodeling induced by achalasia. The concepts are also useful in understanding the treatment that aim to reduce the lower esophageal sphincter pressure that does not relax sufficiently in achalasia. These treatments cover endoscopic or laparoscopic myotomy, pneumatic balloon dilation, and Botox injections. In addition to the intended reduction of the afterload for aboral transport of ingested materials, the treatments tend to induce gastroesophageal reflux in some patients because they obliterate an important component in the reflux barrier.
Pre‐dispersal context and presence of opposite sex modulate density dependence and sex bias of dispersal
Authors: Mishra Abhishek , Tung Sudipta , Sruti V. R. Shree , Sadiq Mohammed Aamir , Srivathsa Sahana , Dey Sutirth
Published: May 2018

Density‐dependent dispersal (DDD) has been observed across taxa, and is expected to affect phenomena such as population dynamics, biological invasions, range expansions, and community assembly. However, little is known about whether the patterns of DDD are robust to changes in the environment. For example, the pre‐dispersal context could affect the physiology of organisms, which in turn could alter their DDD. Similarly, in sexually reproducing organisms, males and females might be differentially affected by the environment, with possible changes in their dispersal properties. To investigate some of these issues, we performed three independent experiments using laboratory populations of Drosophila melanogaster, which tested the effects of pre‐dispersal context, sex of the dispersers and presence of mates on DDD. A two‐patch dispersal setup was used to estimate the dispersal propensity and temporal dispersal profile of adult fruit flies. Comparing the data from two different pre‐dispersal contexts (variable and uniform pre‐dispersal adult densities), we found that longer pre‐dispersal exposure to higher densities led to stronger negative DDD in both males and females. Surprisingly, this change in DDD strength was accompanied by a switch in the direction of sex‐biased dispersal: from female‐biased dispersal at a low density to male‐biased dispersal at a high density. Moreover, we found that patterns of both density dependence and sex bias were contingent upon the interaction of males and females, as neither sex exhibited DDD in the absence of the other. Taken together, these results suggest that DDD and sex‐biased dispersal can be labile and be driven by the environmental context. Finally, we discuss the potential implications of these findings in terms of various ecological and evolutionary processes.
Dehydration‐responsive nuclear proteome landscape of chickpea (Cicer arietinum L.) reveals phosphorylation‐mediated regulation of stress response
Authors: Barua Pragya , Lande Nilesh Vikram , Subba Pratigya , Gayen Dipak , Pinto Sneha , Keshava Prasad T.S. , Chakraborty Subhra , Chakraborty Niranjan
Published: May 2018

Nonavailability of water or dehydration remains recurring climatic disorder affecting yield of major food crops, legumes in particular. Nuclear proteins (NPs) and phosphoproteins (NPPs) execute crucial cellular functions that form the regulatory hub for coordinated stress response. Phosphoproteins hold enormous influence over cellular signalling. Four‐week‐old seedlings of a grain legume, chickpea, were subjected to gradual dehydration, and NPs were extracted from unstressed control and from 72‐ and 144‐hr stressed tissues. We identified 4,832 NPs and 478 phosphosites, corresponding to 299 unique NPPs involved in multivariate cellular processes including protein modification and gene expression regulation, among others. The identified proteins included several novel kinases, phosphatases, and transcription factors, besides 660 uncharacterized proteins. Spliceosome complex and splicing related proteins were dominant among differentially regulated NPPs, indicating their dehydration modulated regulation. Phospho‐motif analysis revealed stress‐induced enrichment of proline‐directed serine phosphorylation. Association mapping of NPPs revealed predominance of differential phosphorylation of spliceosome and splicing associated proteins. Also, regulatory proteins of key processes viz., protein degradation, regulation of flowering time, and circadian clock were observed to undergo dehydration‐induced dephosphorylation. The characterization of novel regulatory proteins would provide new insights into stress adaptation and enable directed genetic manipulations for developing climate‐resilient crops.
Effects of reward context on feedback processing as indexed by time‐frequency analysis
Authors: Watts Adreanna T. M. , Bernat Edward M.
Published: May 2018

The role of reward context has been investigated as an important factor in feedback processing. Previous work has demonstrated that the amplitude of the feedback negativity (FN) depends on the value of the outcome relative to the range of possible outcomes in a given context, not the objective value of the outcome. However, some research has shown that the FN does not scale with loss magnitude in loss‐only contexts, suggesting that some contexts do not show a pattern of context dependence. Methodologically, time‐frequency decomposition techniques have proven useful for isolating time‐domain ERP activity as separable processes indexed in delta (< 3 Hz) and theta (3–7 Hz). Thus, the current study assessed the role of context in a modified gambling feedback task using time‐frequency analysis to better isolate the underlying processes. Results revealed that theta was more context dependent and reflected a binary evaluation of bad versus good outcomes in the gain and even contexts. Delta was more context independent: good outcomes scaled linearly with reward magnitude and good‐bad differences scaled with context valence. Our findings reveal that theta and delta are differentially sensitive to context and that context valence may play a critical role in determining how the brain processes feedback.
Productivity and efficiency at english football clubs: a random coefficient approach
Authors: Feng Guohua , Jewell Todd
Published: May 2018

This paper analyzes productivity and efficiency of English professional football clubs from 1981–1982 to 2010–2011, using a random coefficient stochastic distance frontier (SDF) model. Our Bayes factor analysis indicates that this model is strongly favored over the commonly used fixed coefficient SDF model. Our empirical results show that clubs in our sample operate at different levels of technical efficiency and technical change. Our further analysis using ordered logistic regression suggests that technical efficiency is more important than technical change in predicting whether clubs in our sample are promoted or relegated.
Membrane trafficking in morphogenesis and planar polarity
Authors: Xie Yi , Miao Hui , Blankenship J. Todd
Published: May 2018

Our understanding of how membrane trafficking pathways function to direct morphogenetic movements and the planar polarization of developing tissues is a new and emerging field. While a central focus of developmental biology has been on how protein asymmetries and cytoskeletal force generation direct cell shaping, the role of membrane trafficking in these processes has been less clear. Here, we review recent advances in Drosophila and vertebrate systems in our understanding of how trafficking events are coordinated with planar cytoskeletal function to drive lasting changes in cell and tissue topologies. We additionally explore the function of trafficking pathways in guiding the complex interactions that initiate and maintain core PCP (planar cell polarity) asymmetries and drive the generation of systematically oriented cellular projections during development.
LARGE DIAMETER PILE LOAD TEST WITH A CASE STUDY USING OSTERBERG - CELL
Authors: Bagui S. K. , Dinesh B. C. , Md. Kamal Khan , Sharif Shajib Ahsan Ahmad , Wahid Ruso Inthaqab
Published: May 2018

Static loading test using single level bidirectional –Cell was tested in March 2017 atPaira bridge in Bangladesh for initial load testing. Soil consists of soft silt with traced clay from0.0 m to 10.5 m underlain by various layer with very dense silty sand at the toe level and below.Pile was constructed reverse circulation method. Drilling slurry was composed of bentonite sluryfor 2.5 m diameter pile. The load cells were attached to a reinforcing cage at 18 m above toe.Static load test was 28days of casting the pile and tested. Testing was carried as per ASTM 1143with load increment 7.5 % estimated ultimate load. It was observed that downward movement ofreaching 220 mm and locked downward movement and O-Cell was given force for upwardmovement to find out skin fraction. Detailed analysis was carried out and it was found thatultimate load consisted of 49 MN skin frication and 30 MN end bearing sand safe design loadwas calculated as 33 MN.
Peranan Estim Diri Sebagai Pengantara Antara Perapatan Ibu Bapa-anak dan Sikap Terhadap Tingkah Laku Seksual Dalam Kalangan Remaja Hamil Luar Nikah
Authors: Shahruddin Nor Jum'awaton , Mansor Mariani , Madon Zainal , Hamsan Hanina Halimatusaadiah
Published: May 2018

This study examined the mediating influence of self-esteem on the relationship between parent-child attachment and sexual attitude behavior among adolescent out of wedlock pregnancy in Peninsular Malaysia. Based on cross-sectional design, the sample of this study consisted of 130 teenagers pregnant out of wedlock aged between 14 years and 19 years from 4 welfare institutions in the states of Selangor, Perak, Johor and Kelantan participated in this research. Findings revealed that the level of parent-child attachmen is moderate, a hight of self esteem and  respondents indicated a high level of attitude sexual behavior. Results of Pearson’s correlation analysis revealed that there were significant relationships between parent-child attachment with attitudes toward sexual behaviour (r = -.220, p <.05) and a significant correlation between self esteem and attitude sexual behavior (r = .708, p <.05). In conclusion, the parent-child attachment and self esteem related to attitude sexual behavior. The findings of this study prove that parents should maximize time to ensure that youth do not feel isolated in the family. At the same time, this study also suggests several alternatives in order to curb sexual misconduct among the teenagers today.
Sex differences in diaphragmatic fatigue: the cardiovascular response to inspiratory resistance
Authors: Welch Joseph F. , Archiza Bruno , Guenette Jordan A. , West Christopher R. , Sheel A. William
Published: May 2018

Key points

Diaphragmatic fatigue (DF) elicits a sympathetically mediated metaboreflex resulting in increased heart rate, blood pressure and limb vascular resistance.

Women may be more resistant to DF compared to men, and therefore it was hypothesised that women would experience an attenuated inspiratory muscle metaboreflex during inspiratory pressure‐threshold loading (PTL) performed to task failure.

At the time of PTL task failure, the severity of DF was not different between sexes; however, inspiratory muscle endurance time was significantly longer in women than in men.

For a given cumulative diaphragmatic force output, the severity of DF was less in women than in men.

Women exhibited a blunted cardiovascular response to inspiratory resistance (i.e. metaboreflex) that may have implications for exercise tolerance.

Diaphragmatic fatigue (DF) elicits reflexive increases in sympathetic vasomotor outflow (i.e. metaboreflex). There is some evidence suggesting women may be more resistant to DF compared to men, and therefore may experience an attenuated inspiratory muscle metaboreflex. To this end, we sought to examine the cardiovascular response to inspiratory resistance in healthy young men (n = 9, age = 24 ± 3 years) and women (n = 9, age = 24 ± 3 years). Subjects performed isocapnic inspiratory pressure‐threshold loading (PTL, 60% maximal inspiratory mouth pressure) to task failure. Diaphragmatic fatigue was assessed by measuring transdiaphragmatic twitch pressure (Pdi,tw) using cervical magnetic stimulation. Heart rate (HR) and mean arterial pressure (MAP) were measured beat‐by‐beat throughout PTL via photoplethysmography, and low‐frequency systolic pressure (LFSBP; a surrogate for sympathetic vasomotor tone) calculated from arterial waveforms using power spectrum analysis. At PTL task failure, the degree of DF was similar between sexes (∼23% reduction in Pdi,tw; P = 0.33). However, time to task failure was significantly longer in women than in men (27 ± 11 vs. 16 ± 11 min, respectively; P = 0.02). Women exhibited less of an increase in HR (13 ± 8 vs. 19 ± 12 bpm; P = 0.02) and MAP (10 ± 8 vs. 14 ± 9 mmHg; P = 0.01), and significantly lower LFSBP (23 ± 11 vs. 34 ± 8 mmHg2; P = 0.04) during PTL compared to men. An attenuation of the inspiratory muscle metaboreflex may influence limb and respiratory muscle haemodynamics with implications for exercise performance.
Estimation of the pressure at a listener's ears in an active headrest system using the remote microphone technique
Authors: Jung Woomin , Elliott Stephen J. , Cheer Jordan
Published: May 2018

The remote microphone technique is considered in this paper as a way of estimating the error signals at a listener's ears in an active headrest system using remotely installed monitoring microphones. A least-squares formulation for the optimal observation filter is presented, including a regularization factor that is chosen to satisfy both the estimation accuracy and robustness to uncertainties. The accuracy of the nearfield estimation is first investigated for a diffuse field via simulations. Additionally, simulations of a free field are also used to investigate the effect of the spatial directivity of the primary field. Finally, experiments in an anechoic chamber are conducted with 24 monitoring microphones around a dummy head positioned in an active headrest system. When six loudspeakers driven by uncorrelated random disturbances are used to generate the primary field, the best arrangement of monitoring microphones is considered, taking into account both accuracy and robustness.
Effects of fundamental frequency contour on understanding Mandarin sentences in bimodal hearing simulations
Authors: Chen Fei , Chen Jing
Published: May 2018

Fundamental frequency (F0) contour carries important information for understanding a tonal language. The present work assessed the effects of F0 contour on understanding Mandarin sentences in bimodal hearing simulations, including three conditions of acoustic-only, electric-only, and combined stimulations. Test stimuli were synthesized Mandarin sentences, each word with a normal, flat, or randomly assigned lexical tone, and presented to normal-hearing Mandarin-speaking listeners to recognize. Experimental results showed that changing F0 contour significantly affected the perception of Mandarin sentences under all conditions of acoustic-only, electric-only, and combined stimulations. The combined-stimulation advantage was only observed for test stimuli with the normal F0 contour.
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

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.
RpoN-Dependent Direct Regulation of Quorum Sensing and the Type VI Secretion System in Pseudomonas aeruginosa PAO1
Authors: Shao Xiaolong , Zhang Xiaoning , Zhang Yingchao , Zhu Miao , Yang Pan , Yuan Jian , Xie Yingpeng , Zhou Tianhong , Wang Wei , Chen Sheng , Liang Haihua , Deng Xin
Published: May 2018

As a global regulator, RpoN controls a wide range of biological pathways, including virulence inP. aeruginosaPAO1. This work shows that RpoN plays critical and global roles in the regulation of bacterial pathogenicity and fitness. ChIP-seq provided a useful database to characterize additional functions and targets of RpoN in the future. The functional characterization of RpoN-mediated regulation will improve the current understanding of the regulatory network of quorum sensing and virulence inP. aeruginosaand other bacteria.
Microglia Are Critical in Host Defense against Prion Disease
Authors: Carroll James A. , Race Brent , Williams Katie , Striebel James , Chesebro Bruce
Published: May 2018

Microglia contribute to many aspects of health and disease. When activated, microglia can be beneficial by repairing damage in the central nervous system (CNS) or they can turn harmful by becoming neurotoxic. In prion and prionlike diseases, the involvement of microglia in disease is unclear. Previous studies suggest that microglia can either speed up or slow down disease. In this study, we infected mice with prions and depleted microglia from the brains of mice using PLX5622, an effective CSF-1R tyrosine kinase inhibitor. Microglia were markedly reduced in brains, and prion disease was accelerated, so that mice needed to be euthanized 20 to 33 days earlier than infected control mice due to advanced clinical disease. Similar results occurred when mice were treated with PLX5622 at 80 days after infection, which was just prior to the start of clinical signs. Thus, microglia are important for removing prions, and the disease is faster when microglia are depleted.
Biological Roles Played by Sphingolipids in Dimorphic and Filamentous Fungi
Authors: Fernandes Caroline Mota , Goldman Gustavo H. , Del Poeta Maurizio
Published: May 2018

Filamentous 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

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

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

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

Introduction

Public 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.

Methods

All 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).

Results

4012 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.

Conclusion

Existing 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

Aims

Multiple 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.

Methods

A 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.

Results

At 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.

Conclusions

Our 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.
Development of a Novel Clinical Staging Model for Cirrhosis Using the Nationwide Inpatient Sample
Authors: Haj Mona , Hart Mary , Rockey Don C
Published: May 2018

Scoring systems such as Model for End-stage Liver Disease (MELD) and Child-Pugh are often used by clinicians to determine prognosis in patients with cirrhosis. Since clinical complications are important in determining cirrhosis outcomes, our goal was to use these to develop a novel prognostic staging model. Data from the Nationwide Inpatient Sample (NIS), years 2003–2011, were queried for records of patients over the age of 18 with cirrhosis excluding patients with prior or inpatient liver transplantation. The primary outcome was inpatient mortality with focus on cirrhosis-related complications: non-bleeding esophageal varices, variceal hemorrhage, ascites, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS). Of 59 862 903 hospitalizations, 824 783 (1.4%) with cirrhosis were identified. Overall mortality was 7% with two-thirds (66%) of deaths occurring in patients with a decompensating event, defined as variceal hemorrhage, ascites, HE, SBP, and/or HRS. Overall mortality rates decreased from 2003 to 2011 (9.0–6.0%), in both compensated and decompensated groups. Mortality was higher in patients with variceal haemorrhage (OR 1.56; p<0.05), HE (OR 1.75; p<0.05), SBP (OR 2.64; p<0.05) and HRS (OR 9.10; p<0.05) compared with patients with no complications. HRS had the highest mortality, whether alone or in combination with another event such as HE (OR 12.40; p<0.05) or SBP (OR 12.64; p<0.05). Cirrhosis inpatient outcomes are related to the severity of liver disease, with more severe complications such as HE, SBP, and HRS having the most significant effect on inpatient mortality, and are utilised in this novel four-stage clinical model.
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

Introduction

Cerebral 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).

Methods

We 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.

Results

Inter-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.

Conclusions

The 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.
Agreement between core laboratory and study investigators for imaging scores in a thrombectomy trial
Authors: Fahed Robert , Ben Maacha Malek , Ducroux Célina , Khoury Naim , Blanc Raphaël , Piotin Michel , Lapergue Bertrand
Published: May 2018

Purpose

We aimed to assess the agreement between study investigators and the core laboratory (core lab) of a thrombectomy trial for imaging scores.

Methods

The Alberta Stroke Program Early CT Score (ASPECTS), the European Collaborative Acute Stroke Study (ECASS) hemorrhagic transformation (HT) classification, and the Thrombolysis In Cerebral Infarction (TICI) scores as recorded by study investigators were compared with the core lab scores in order to assess interrater agreement, using Cohen’s unweighted and weighted kappa statistics.

Results

There were frequent discrepancies between study sites and core lab for all the scores. Agreement for ASPECTS and ECASS HT classification was less than substantial, with disagreement occurring in more than one-third of cases. Agreement was higher on MRI-based scores than on CT, and was improved after dichotomization on both CT and MRI. Agreement for TICI scores was moderate (with disagreement occurring in more than 25% of patients), and went above the substantial level (less than 10% disagreement) after dichotomization (TICI 0/1/2a vs 2b/3).

Conclusion

Discrepancies between scores assessed by the imaging core lab and those reported by study sites occurred in a significant proportion of patients. Disagreement in the assessment of ASPECTS and day 1 HT scores was more frequent on CT than on MRI. The agreement for the dichotomized TICI score (the trial’s primary outcome) was substantial, with less than 10% of disagreement between study sites and core lab.

Trial registration number

NCT02523261, Post-results.