bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole‐exome sequencing identifies novel pathogenic variants across the ATP7B gene and some modifiers of Wilson's disease phenotype
Authors: Kluska Anna , Kulecka Maria , Litwin Tomasz , Dziezyc Karolina , Balabas Aneta , Piatkowska Magdalena , Paziewska Agnieszka , Dabrowska Michalina , Mikula Michal , Kaminska Diana , Wiernicka Anna , Socha Piotr , Czlonkowska Anna , Ostrowski Jerzy 
Published: September 2018

AbstractBackground & AimsWilson's disease (WD) is an autosomal recessive disorder associated with disease‐causing alterations across the ATP7B gene, with highly variable symptoms and age of onset. We aimed to assess whether the clinical variability of WD relates to modifier genes.MethodsA total of 248 WD patients were included, of whom 148 were diagnosed after age of 17. Human exome libraries were constructed using AmpliSeq technology and sequenced using the IonProton platform.ResultsATP7B p.His1069Gln mutation was present in 215 patients, with 112 homozygotes and 103 heterozygotes. Three other mutations: p.Gln1351Ter, p.Trp779Ter and c.3402delC were identified in >10 patients. Among patients, 117 had a homozygous mutation, 101 were compound heterozygotes, 27 had one heterozygous mutation, and 3 other patients had no identifiable pathogenic variant of ATP7B. Sixteen mutations were novel, found as part of a compound mutation or as a sole, homozygous mutation. For disease phenotype prediction, age at diagnosis was a deciding factor, while frameshift allelic variants of ATP7B and being male increased the odds of developing a neurological phenotype. Rare allelic variants in ESD and INO80 increased and decreased chances for the neurological phenotype, respectively, while rare variants in APOE and MBD6 decreased the chances of WD early manifestation. Compound mutations contributed to earlier age of onset.ConclusionsIn a Polish population, genetic screening for WD may help genotype for four variants (p.His1069Gln, p.Gln1351Ter, p.Trp779Ter and c.3402delC), with direct sequencing of all ATP7B amplicons as a second diagnostic step. We also identified some allelic variants that may modify a WD phenotype.
The adaptive significance of chromosomal inversion polymorphisms inDrosophila melanogaster
Authors: Kapun Martin , Flatt Thomas 
Published: September 2018

AbstractChromosomal inversions, structural mutations that reverse a segment of a chromosome, cause suppression of recombination in the heterozygous state. Several studies have shown that inversion polymorphisms can form clines or fluctuate predictably in frequency over seasonal time spans. These observations prompted the hypothesis that chromosomal rearrangements might be subject to spatially and/or temporally varying selection. Here, we review what has been learned about the adaptive significance of inversion polymorphisms in the vinegar flyDrosophila melanogaster, the species in which they were first discovered by Sturtevant in 1917. A large body of work provides compelling evidence that several inversions in this system are adaptive; however, the precise selective mechanisms that maintain them polymorphic in natural populations remain poorly understood. Recent advances in population genomics, modelling and functional genetics promise to greatly improve our understanding of this long‐standing and fundamental problem in the near future.
Genomic features of the Helicobacter pylori strain PMSS1 and its virulence attributes as deduced from its in vivo colonisation patterns
Authors: Dyer Victoria , Brüggemann Holger , Sörensen Meike , Kühl Anja A. , Hoffman Kirstin , Brinkmann Volker , Reines Maria del Mar , Zimmerman Stephanie , Meyer Thomas F. , Koch Manuel 
Published: September 2018

SummaryThe human gastric pathogen Helicobacter pylori occurs in two basic variants, either exhibiting a functional cagPAI‐encoded type‐4‐secretion‐system (T4SS) or not. Only a few cagPAI‐positive strains have been successfully adapted for long‐term infection of mice, including the pre‐mouse Sydney strain 1 (PMSS1). Here we confirm that PMSS1 induces gastric inflammation and neutrophil infiltration in mice, progressing to intestinal metaplasia. Complete genome analysis of PMSS1 revealed 1,423 coding sequences, encompassing the cagPAI gene cluster and, unusually, the location of the cytotoxin‐associated gene A (cagA) approximately 15 kb downstream of the island. PMSS1 harbours three genetically exchangeable loci that are occupied by the hopQ coding sequences. HopQ represents a critical co‐factor required for the translocation of CagA into the host cell and activation of NF‐κB via the T4SS. Long‐term colonisation of mice led to an impairment of cagPAI functionality. One of the bacterial clones re‐isolated at four months post‐infection revealed a mutation in the cagPAI gene cagW, resulting in a frame shift mutation, which prevented CagA translocation, possibly due to an impairment of T4SS function. Rescue of the mutant cagW re‐established CagA translocation. Our data reveal intriguing insights into the adaptive abilities of PMSS1, suggesting functional modulation of the H. pylori cagPAI virulence attribute.
Inorganic polyphosphate interacts with nucleolar and glycosomal proteins in trypanosomatids
Authors: Negreiros Raquel S. , Lander Noelia , Huang Guozhong , Cordeiro Ciro D. , Smith Stephanie A. , Morrissey James H. , Docampo Roberto 
Published: September 2018

SummaryInorganic polyphosphate (polyP) is a polymer of three to hundreds of phosphate units bound by high‐energy phosphoanhydride bonds and present from bacteria to humans. Most polyP in trypanosomatids is concentrated in acidocalcisomes, acidic calcium stores that possess a number of pumps, exchangers, and channels, and are important for their survival. In this work, using polyP as bait we identified > 25 putative protein targets in cell lysates of both Trypanosoma cruzi and Trypanosoma brucei. Gene ontology analysis of the binding partners found a significant over‐representation of nucleolar and glycosomal proteins. Using the polyphosphate‐binding domain (PPBD) of Escherichia coli exopolyphosphatase (PPX), we localized long‐chain polyP to the nucleoli and glycosomes of trypanosomes. A competitive assay based on the pre‐incubation of PPBD with exogenous polyP and subsequent immunofluorescence assay of procyclic forms (PCF) of T. brucei showed polyP concentration‐dependent and chain length‐dependent decrease in the fluorescence signal. Subcellular fractionation experiments confirmed the presence of polyP in glycosomes of T. brucei PCF. Targeting of yeast PPX to the glycosomes of PCF resulted in polyP hydrolysis, alteration in their glycolytic flux and increase in their susceptibility to oxidative stress.
Catalytic diversity and cell wall binding repeats in the phage‐encoded endolysins
Authors: Broendum Sebastian S. , Buckle Ashley M. , McGowan Sheena 
Published: September 2018

SummaryBacteriophage‐encoded endolysins can recognize and bind specific bacteria, and act to cleave the glycosidic and/or amide bonds in the peptidoglycan (PG) bacterial cell wall. Cleavage of the cell wall generally results in the death of the bacteria. Their utility as bacteriolytic agents could be exploited for human and veterinary medicines as well as various biotechnological applications. As interest grows in the commercial uses of these proteins, there has been much effort to successfully employ rational design and engineering to produce endolysins with bespoke properties. In this review, we interrogate the current structural data and identify structural features that would be of benefit to engineering the activity and specificity of phage endolysins. We show that the growing body of structural data can be used to predict catalytic residues and mechanism of action from sequences of hypothetical endolysins, and probe the importance of secondary structure repeats in bacterial cell wall‐binding domains.
Cell cycle‐dependent regulation of FtsZ in Escherichia coli in slow growth conditions
Authors: Männik Jaana , Walker Bryant E. , Männik Jaan 
Published: September 2018

SummaryFtsZ is the key regulator of bacterial cell division. It initiates division by forming a dynamic ring‐like structure, the Z‐ring, at the mid‐cell. What triggers the formation of the Z‐ring during the cell cycle is poorly understood. In Escherichia coli, the common view is that FtsZ concentration is constant throughout its doubling time and therefore regulation of assembly is controlled by some yet‐to‐be‐identified protein‐protein interactions. Using a newly developed functional, fluorescent FtsZ reporter, we performed a quantitative analysis of the FtsZ concentration throughout the cell cycle under slow growth conditions. In contrast to the common expectation, we show that FtsZ concentrations vary in a cell cycle‐dependent manner, and that upregulation of FtsZ synthesis correlates with the formation of the Z‐ring. The first half of the cell cycle shows an approximately fourfold upregulation of FtsZ synthesis, followed by its rapid degradation by ClpXP protease in the last 10% of the cell cycle. The initiation of rapid degradation coincides with the dissociation of FtsZ from the septum. Altogether, our data suggest that the Z‐ring formation in slow growth conditions in E. coli is partially controlled by a regulatory sequence wherein upregulation of an essential cell cycle factor is followed by its degradation.
Cine MRI assessment of motility in the unprepared small bowel in the fasting and fed state: Beyond the breath‐hold
Authors: Khalaf Asseel , Nowak Adam , Menys Alex , Marciani Luca , Taylor Stuart A. , Spiller Robin C. , Gowland Penny A. , Moran Gordon W. , Hoad Caroline L. 
Published: September 2018

AbstractBackgroundThe symptoms of functional bowel disorders are common in postprandial but investigations are generally undertaken in the fasted state using invasive procedures. MRI provides a noninvasive tool to study the gastrointestinal tract in an unperturbed, fed state. The aim of this study was to develop a technique to assess small bowel motility from cine MRI data in the unprepared bowel in fasting and fed states.MethodsFifteen healthy volunteers underwent a baseline MRI scan after which they consumed a 400 g soup. Subjects then underwent a postprandial scan followed by further scans at regular intervals. Small bowel motility was assessed using single‐slice bTFE cine MRI. An optimized processing technique was used to generate motility data based on power spectrum analysis of voxel‐signal changes with time. Interobserver variability (n = 15) and intra‐observer (n = 6) variability were assessed. Changes in the motility index were compared between fasted and immediate postprandial state.Key ResultsExcellent agreement between observers was seen across the range of motility measurements acquired, with intraclass correlation coefficient (ICC) of 0.979 (P < 0.0001) and Bland‐Altman limits of agreement 95% CI: −28.9 to 45.9 au. Intra‐observer variability was low with ICC of 0.992 and 0.960 (2 observers, P < 0.0001). Changes from the fasted to immediately postprandial state showed an average increase of 122.4% ± 98.7% (n = 15).Conclusions & InferencesThis optimized technique showed excellent inter and intra observer agreement. It was sensitive to changes in motility induced feeding. This technique will be useful to study contractile activity and regional patterns along the gastrointestinal tract under physiological conditions.
Hydrogen sulfide downregulates colonic afferent sensitivity by a nitric oxide synthase‐dependent mechanism in mice
Authors: Xu Xiaomeng , Li Shuang , Shi Yao , Tang Yan , Lu Wen , Han Ting , Xue Bing , Li Jingxin , Liu Chuanyong 
Published: September 2018

AbstractBackgroundThe effect of hydrogen sulfide (H2S) on visceral nociception is elusive. The conflicting evidence of its pro‐ and antinociceptive effects raises a series of questions with respect to the effect of H2S on colonic afferent activity and the underlying mechanism, which was further elucidated in this study.MethodsColonic mesenteric afferent nerve spikes of normal male C57BL/6J mice, Cbs+/− mice, and Wistar rats were recorded in vitro. The abdominal withdrawal reflex (AWR) induced by colorectal distension (CRD) was evaluated in Cbs+/− mice and WT littermates.Key ResultsSodium hydrosulfide (NaHS) significantly decreased colonic afferent spontaneous discharge, chemosensitivity to bradykinin, mechanosensitivity to ramp distention, and intraluminal pressure in mice. Reducing the relaxant action of NaHS on intestinal smooth muscle using the nonspecific K+ channel blocker TEA (10 mmol/L) did not block the inhibition of NaHS on afferent nerve activity. The inhibitory effects of NaHS (0.5 mmol/L) on colonic afferent sensitivity were largely eliminated by the pretreatment with nonspecific NOS inhibitor NG‐Methyl‐l‐arginine acetate salt (1 mmol/L), the specific nNOS inhibitor NPLA (1 μmol/L), or N‐type Ca2+ channel blocker ω‐conotoxin GVIA (1 μmol/L). Compared with WT mice, Cbs+/− mice showed increased mesenteric afferent sensitivity to colonic distention and enhanced hyperalgesic response to CRD. Intraperitoneal administration of NaHS (60 μmol/kg) alleviated the nociception response to CRD in both Cbs+/− and WT mice.Conclusions and InferencesH2S downregulates colonic mesenteric afferent sensitivity by a nNOS‐dependent mechanism in mice. Our findings may demonstrate a new mechanism for the antinociceptive effect of H2S in colon.
Variation in abundance of predicted resistance genes in the Brassica oleracea pangenome
Authors: Bayer Philipp E. , Golicz Agnieszka A. , Tirnaz Soodeh , Chan Chon‐Kit Kenneth , Edwards David , Batley Jacqueline 
Published: September 2018

SummaryBrassica oleracea is an important agricultural species encompassing many vegetable crops including cabbage, cauliflower, broccoli and kale; however, it can be susceptible to a variety of fungal diseases such as clubroot, blackleg, leaf spot and downy mildew. Resistance to these diseases is meditated by specific disease resistance genes analogs (RGAs) which are differently distributed across B. oleracea lines. The sequenced reference cultivar does not contain all B. oleracea genes due to gene presence/absence variation between individuals, which makes it necessary to search for RGA candidates in the B. oleracea pangenome. Here we present a comparative analysis of RGA candidates in the pangenome of B. oleracea. We show that the presence of RGA candidates differs between lines and suggests that in B. oleracea, SNPs and presence/absence variation drive RGA diversity using separate mechanisms. We identified 59 RGA candidates linked to Sclerotinia, clubroot, and Fusarium wilt resistance QTL, and these findings have implications for crop breeding in B. oleracea, which may also be applicable in other crops species.
Development and evaluation of novel salt‐tolerantEucalyptustrees by molecular breeding using anRNA‐Binding‐Proteingene derived from common ice plant (Mesembryanthemum crystallinumL.)
Authors: Tran Ngoc‐Ha Thi , Oguchi Taichi , Akatsuka Nobuhumi , Matsunaga Etsuko , Kawaoka Akiyoshi , Yamada Akiyo , Ozeki Yoshihiro , Watanabe Kazuo N. , Kikuchi Akira 
Published: September 2018

SummaryThe breeding of plantation forestry trees for the possible afforestation of marginal land would be one approach to addressing global warming issues. Here, we developed novel transgenicEucalyptustrees (Eucalyptus camaldulensisDehnh.) harbouring anRNA‐Binding‐Protein(McRBP) gene derived from a halophyte plant, common ice plant (Mesembryanthemum crystallinumL.). We conducted screened‐house trials of the transgenicEucalyptususing two different stringency salinity stress conditions to evaluate the plants’ acute and chronic salt stress tolerances. Treatment with 400 mM NaCl, as the high‐stringency salinity stress, resulted in soil electrical conductivity (EC) levels >20 mS/cm within 4 weeks. With the 400 mM NaCl treatment, >70% of the transgenic plants were intact, whereas >40% of the non‐transgenic plants were withered. Treatment with 70 mM NaCl, as the moderate‐stringency salinity stress, resulted in soilEClevels of approx. 9 mS/cm after 2 months, and these salinity levels were maintained for the next 4 months. All plants regardless of transgenic or non‐transgenic status survived the 70 mM NaCl treatment, but after 6‐month treatment the transgenic plants showed significantly higher growth and quantum yield of photosynthesis levels compared to the non‐transgenic plants. In addition, the salt accumulation in the leaves of the transgenic plants was 30% lower than that of non‐transgenic plants after 15‐week moderate salt stress treatment. There results suggest thatMcRBPexpression in the transgenicEucalyptusenhances their salt tolerance both acutely and chronically.
Stable and clumped isotopes in desert carbonate spring and lake deposits reveal palaeohydrology: A case study of the Lower Jurassic Navajo Sandstone, south‐western USA
Authors: Parrish Judith Totman , Hyland Ethan G. , Chan Marjorie A. , Hasiotis Stephen T. 
Published: September 2018

AbstractCarbon, oxygen and clumped isotope (Δ47) values were measured from lacustrine and tufa (spring)‐mound carbonate deposits in the Lower Jurassic Navajo Sandstone of southern Utah and northern Arizona in order to understand the palaeohydrology. These carbonate deposits are enriched in both 18O and 13C across the basin from east to west; neither isotope is strongly sensitive to the carbonate facies. However, 18O is enriched in lake carbonate deposits compared to the associated spring mounds. This is consistent with evaporation of the spring waters as they exited the mounds and were retained in interdune lakes. Clumped isotopes (Δ47) exhibit minor systematic differences between lake and tufa‐mound temperatures, suggesting that the rate of carbonate formation under ambient conditions was moderate. These clumped isotope values imply palaeotemperature elevated beyond reasonable surface temperatures (54 to 86°C), which indicates limited bond reordering at estimated burial depths of ca 4 to 5 km, consistent with independent estimates of sediment thickness and burial depth gradients across the basin. Although clumped isotopes do not provide surface temperature information in this case, they still provide useful burial information and support interpretations of the evolution of groundwater locally. The findings of this study significantly extend the utility of combining stable isotope and clumped isotope methods into aeolian environments.
High‐density electromyography activity in various hamstring exercises
Authors: Hegyi András , Csala Dániel , Péter Annamária , Finni Taija , Cronin Neil J 
Published: September 2018

AbstractProximal‐distal differences in muscle activity are rarely considered when defining the activity level of hamstring muscles. The aim of this study was to determine the inter‐muscular and proximal‐distal electromyography (EMG) activity patterns of hamstring muscles during common hamstring exercises. Nineteen amateur athletes without a history of hamstring injury performed 9 exercises, while EMG activity was recorded along the biceps femoris long head (BFlh) and semitendinosus (ST) muscles using 15‐channel high‐density electromyography (HD‐EMG) electrodes. EMG activity levels normalized to those of a maximal voluntary isometric contraction (%MVIC) were determined for the eccentric and concentric phase of each exercise and compared between different muscles and regions (proximal, middle, distal) within each muscle. Straight‐knee bridge, upright hip extension, and leg curls exhibited the highest hamstrings activity in both the eccentric (40%‐54%MVIC) and concentric phases (69%‐85%MVIC). Hip extension was the only BF‐dominant exercise (Cohen's d = 0.28 (eccentric) and 0.33 (concentric)). Within ST, lower distal than middle/proximal activity was found in the bent‐knee bridge and leg curl exercises (d range = 0.53‐1.20), which was not evident in other exercises. BFlh also displayed large regional differences across exercises (d range = 0.00‐1.28). This study demonstrates that inter‐muscular and proximal‐distal activity patterns are exercise‐dependent, and in some exercises are affected by the contraction mode. Knowledge of activity levels and relative activity of hamstring muscles in different exercises may assist exercise selection in hamstring injury management.
Peak oxygen uptake cut‐points to identify children at increased cardiometabolic risk – The PANIC Study
Authors: Agbaje Andrew O. , Haapala Eero A. , Lintu Niina , Viitasalo Anna , Barker Alan R. , Takken Tim , Tompuri Tuomo , Lindi Virpi , Lakka Timo A. 
Published: September 2018

We aimed to develop cut‐points for directly measured peak oxygen uptake () to identify boys and girls at increased cardiometabolic risk using different scaling methods to control for body size and composition. Altogether 352 children (186 boys, 166 girls) aged 9‐11 years were included in the analyses. We measured V̇O2peak directly during a maximal cycle ergometer exercise test and lean body mass (LM) by bioelectrical impedance. We computed a sex‐ and age‐specific cardiometabolic risk score (CRS) by summing important cardiometabolic risk factors and defined increased cardiometabolic risk as >1 standard deviation above the mean of CRS. Receiver operating characteristics curves were used to detect V̇O2peak cut‐points for increased cardiometabolic risk. Boys with V̇O2peak <45.8 mL kg body mass (BM)−1 min−1 (95% confidence interval [CI] = 45.1 to 54.6, area under the curve [AUC] = 0.86, P < 0.001) and <63.2 mL kg LM−1 min−1 (95% CI =52.4 to 67.5, AUC = 0.65, P = 0.006) had an increased CRS. Girls with V̇O2peak <44.1 mL kg BM−1 min−1 (95% CI = 44.0 to 58.6, AUC = 0.67, P = 0.013) had an increased CRS. V̇O2peak scaled by BM−0.49 and LM−0.77 derived from log‐linear allometric modeling poorly predicted increased cardiometabolic risk in boys and girls. In conclusion, directly measured <45.8 mL kg BM−1 min−1 among boys and <44.1 mL kg BM−1 min−1 among girls were cut‐points to identify those at increased cardiometabolic risk. Appropriately controlling for body size and composition reduced the ability of cardiorespiratory fitness to identify children at increased cardiometabolic risk.
How Increasing Party Diversity May Lead to Worsening Reported Racial Attitudes*
Authors: Stout Christopher T. , Baker Keith 
Published: September 2018

ObjectiveTo explore whether increases in diversity give partisans immunity from claims of racial prejudice. To assess when individuals are more likely to report racially progressive attitudes when their party is accused of racism and racial representation in the party varies.MethodWe implement a survey experiment where individuals are told their party harbors either racial or religious prejudice and then are asked to vote on a party primary election in which the race of the candidates varies.ResultsWe find that white Republicans modify their racial attitudes in response to accusations of racism. However, this effect disappears when white Republicans are presented with evidence of racial/ethnic diversity in their party.ConclusionOur results demonstrate that racial/ethnic diversity in one's political party may delegitimize claims of racial bias and minimize these accusations' ability to alter racial attitudes.