bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of β-synuclein on secretory granules in chromaffin cells and the effects of α- and β-synuclein on BDNF discharge following fusion
Authors: Bittner Mary A. , Bohannon Kevin P. , Axelrod Daniel , Holz Ronald W. 
Published: July 2017

AbstractSynuclein is strongly implicated in the pathogenesis of Parkinson’s disease as well as in other neurodegenerative diseases. However, its normal function in cells is not understood. The N-termini of α-, β-, and γ-synuclein are comprised of seven 11-amino acid repeats that are predicted to form amphipathic helices. α-Synuclein binds to negatively charged lipids, especially small vesicles and tubulates and vesiculates lipids. The membrane-binding and membrane-curving abilities raise the possibility that synuclein could alter cellular processes that involve highly curved structures. In the present study we examined the localization of endogenous synuclein in bovine chromaffin cells by immunocytochemistry and its possible function to control protein discharge upon fusion of the granule with the plasma membrane by regulating the fusion pore. We found with quantitative immunocytochemistry that endogenous β-synuclein associates with secretory granules. Endogenous α-synuclein only rarely is found on secretory granules. Overexpression of α-synuclein but not β-synuclein quickened the median duration of the post-fusion discharge of BDNF-pHluorin by 30%, consistent with α-synuclein speeding fusion pore expansion.
Evolutionary Action ofde novoMissense Variants across Pathways Prioritizes Genes Linked to Autism and Predicts Patient Phenotypic Severity
Authors: Koire Amanda , Buchovecky Christie , Katsonis Panagiotis , Kim Young Won , Wilson Stephen J. , Lichtarge Olivier 
Published: July 2017

AbstractThe pathogenicity of individualde novomissense mutations in autism spectrum disorder remains difficult to validate. Here we asked in 2,384 probands whether these variants exhibited collective functional impact biases across pathways. As measured with Evolutionary Action (EA) in 368 gene groupings, we found significant biases in axonogenesis, synaptic transmission, and other neurodevelopmental pathways. Strikingly, bothde novoand inherited missense variants in prioritized genes correlated with patient IQ. This general integrative approach thus detects missense variants most likely to contribute to autism pathogenesis and is the first, to our knowledge, to link missense variant impact to autism phenotypic severity.
Pollen limitation, reproductive success and flowering frequency in single‐flowered plants
Authors: Sun Hai‐Qin , Huang Bao‐Qiang , Yu Xiao‐Hong , Tian Chang‐Bao , Peng Qi‐Xuan , An De‐Jun 
Published: July 2017

Abstract

Flowering plants exhibit striking interspecific and intraspecific variation in flower number, which strongly influences the reproductive success of animal‐pollinated plants. However, the reproductive consequences of producing a single flower are poorly understood.

Here, we test if plants producing a single flower have a reproductive disadvantage compared with plants producing multiple flowers by combining field investigation of five deceptive orchids and a survey of published literature. Pollen limitation was estimated by comparing fruit production between hand pollination and open pollination. Flowering frequency was monitored over years to assess the potential advantage of producing a single flower.

Both single‐ and multiple‐flowered species suffered strong pollen limitation. However, single‐flowered species had significantly lower fruit set and produced fewer seeds per individual, although they had a significantly higher pollen removal than species with multiple flowers. A phylogenetically independent contrast of 28 species representing four of the five subfamilies of Orchidaceae revealed that fruit set was significantly positively associated with flower number. Both pollen removal and fruit set had a positive relationship with flower number within the multiple‐flowered species.

Synthesis. Current data and phylogenetically independent contrast support the hypothesis that producing a single flower has reproductive disadvantages. Single‐flowered species may compensate for low female success through high flowering frequency over years. This study provides insight into costs and benefits of producing a single flower in deceptive orchids.
Austerity Policies, the UK State and the Energy Utilities: a Changing Paradigm or Business as Usual?
Authors: de Carvalho Lucie 
Published: July 2017

AbstractIn 2008, the economic downturn coincided with a major shift in the energy sector paradigm. This state of emergency forced the UK government to try to steer the objectives of its major energy players. This crisis put the UK state's capacity to influence its mostly privately‐owned energy sector to the test. Using the example of energy utilities, this article aims to explore whether the austerity agenda impacted the relationship between the UK state and its public services. The purpose is to determine whether current multiple crises have forced the UK state to adopt an exceptionally interventionist approach that doesn't tally with the austerity agenda, or whether these crises merely revealed dynamics which had been underlying in the management of its energy utilities since the beginning of the neo‐liberal era.
Scrutinizing key steps for reliable metabarcoding of environmental samples
Authors: Alberdi Antton , Aizpurua Ostaizka , Gilbert M. Thomas P. , Bohmann Kristine 
Published: July 2017

Abstract

Metabarcoding of environmental samples has many challenges and limitations that require carefully considered laboratory and analysis workflows to ensure reliable results. We explore how decisions regarding study design, laboratory set‐up, and bioinformatic processing affect the final results, and provide guidelines for reliable study of environmental samples.

We evaluate the performance of four primer sets targeting COI and 16S regions characterizing arthropod diversity in bat faecal samples, and investigate how metabarcoding results are affected by parameters including: (1) number of PCR replicates per sample, (2) sequencing depth, (3) PCR replicate processing strategy (i.e. either additively, by combining the sequences obtained from the PCR replicates, or restrictively, by only retaining sequences that occur in multiple PCR replicates for each sample), (4) minimum copy number for sequences to be retained, (5) chimera removal, and (6) similarity thresholds for Operational Taxonomic Unit (OTU) clustering. Lastly, we measure within‐ and between‐taxa dissimilarities when using sequences from public databases to determine the most appropriate thresholds for OTU clustering and taxonomy assignment.

Our results show that the use of multiple primer sets reduces taxonomic biases and increases taxonomic coverage. Taxonomic profiles resulting from each primer set are principally affected by how many PCR replicates are carried out per sample and how sequences are filtered across them, the sequence copy number threshold and the OTU clustering threshold. We also report considerable diversity differences between PCR replicates from each sample. Sequencing depth increases the dissimilarity between PCR replicates unless the bioinformatic strategies to remove allegedly artefactual sequences are adjusted according to the number of analysed sequences. Finally, we show that the appropriate identity thresholds for OTU clustering and taxonomy assignment differ between markers.

Metabarcoding of complex environmental samples ideally requires (1) investigation of whether more than one primer sets targeting the same taxonomic group is needed to offset primer biases, (2) more than one PCR replicate per sample, (3) bioinformatic processing of sequences that balance diversity detection with removal of artefactual sequences, and (4) empirical selection of OTU clustering and taxonomy assignment thresholds tailored to each marker and the obtained taxa.
Heavy alcohol consumption increases the risk of active tuberculosis in Taiwanese adults: a nation‐wide population‐based cohort study
Authors: Yen Yung‐Feng , Hu Hsiao‐Yun , Lee Ya‐Ling , Ku Po‐Wen , Chuang Pei‐Hung , Lai Yun‐Ju , Chu Dachen 
Published: July 2017

AbstractAimsTo investigate the impact of alcohol exposure on tuberculosis (TB) development in Taiwanese adults.DesignParticipants from the Taiwan National Health Interview Survey. Alcohol consumption and other covariates were collected by in‐person interviews at baseline. Incident cases of active TB were identified from the National Health Insurance database. A multivariable Cox regression model was used to estimate the association between alcohol consumption and active TB, with adjustment for age, sex, smoking, socio‐economic status and other covariates.SettingTaiwan National Health Interview Survey.ParticipantsA total of 46 196 adult participants aged ≥ 18 years from three rounds (2001, 2005, 2009) of the Taiwan National Health Interview Survey.MeasurementsAlcohol consumption was classified into never, social, regular or heavy alcohol use. Heavy alcohol consumption was defined as intoxication at least once/week.FindingsOf the 46 196 study subjects, 61.8, 24.2, 13.5 and 0.5% were classified as never, social, regular and heavy alcohol users, respectively. During the 398 443 person‐years of follow‐up, 279 (0.60%) subjects developed new‐onset active TB. After adjusting for the subject demographics and comorbidities, heavy [hazard ratio (HR) = 5.27; 95% confidence interval (CI) = 2.51–11.09] and regular alcohol users (HR = 1.80; 95% CI = 1.32–2.45) had increased risks of incident TB compared to never users. Moreover, a positive trend between increasing levels of alcohol consumption and the risk of active TB was noted (P < 0.001).ConclusionsIn Taiwan, heavy and regular alcohol consumption are associated with higher risks of active tuberculosis.
Hospitalization rates during potentially inappropriate medication use in a large population‐based cohort of older adults
Authors: Varga Stefan , Alcusky Matthew , Keith Scott W. , Hegarty Sarah E. , Del Canale Stefano , Lombardi Marco , Maio Vittorio 
Published: July 2017

Background and aimsThe temporal relationship between potentially inappropriate medication (PIM) use and hospitalization remains uncertain. We examined whether current PIM use increases the rate of hospitalization and estimated the rate of hospitalization during exposure to individual PIMs.MethodsA retrospective population‐based cohort study of 1 480 137 older adults was conducted using the 2003–2013 Italian Emilia‐Romagna Regional administrative healthcare database (~4.5 million residents), which includes demographic, hospital and outpatient prescription information. Each day of follow‐up was defined as exposed/unexposed to PIMs that ‘should always be avoided’, according to the Maio criteria, an Italian modified version of the Beers criteria. The study outcome was all‐cause hospitalizations. Crude PIM‐related hospitalization rates were calculated for individual PIMs. Repeated‐events Cox proportional hazards models with time‐dependent covariates estimated adjusted hazard ratios for hospitalization during PIM exposure, as defined by three versions of the Maio criteria (v2007, v2011, v2014).ResultsDuring >10 million person‐years of follow‐up, 54.2% of individuals used ≥1 PIM and 10.9% of all person‐time was exposed to v2014 PIMs. Among 1 604 901 hospitalizations, 15.6% occurred during v2014 PIM exposure. Crude hospitalization rates during v2014 PIM‐exposed and unexposed person‐time were 228.1 and 152.1 per 1000 person‐years, respectively. The PIM with the highest rate of hospitalization was ketorolac, while nonsteroidal anti‐inflammatory drugs had the most exposure time. The hazard of hospitalization was 16% greater (hazard ratio = 1.16; 95% confidence interval 1.14, 1.18) among patients exposed to v2014 PIMs. The v2007 and v2011 estimates were similar.ConclusionsIn this large population‐based cohort of older adults, we found a 16% increased hospitalization risk associated with PIM exposure.
Tuberous sclerosis complex: Recent advances in manifestations and therapy
Authors: Wataya‐Kaneda Mari , Uemura Motohide , Fujita Kazutoshi , Hirata Haruhiko , Osuga Keigo , Kagitani‐Shimono Kuriko , Nonomura Norio ,   the Tuberous Sclerosis Complex Board of Osaka University Hospital
Published: July 2017

AbstractTuberous sclerosis complex is an autosomal dominant inherited disorder characterized by generalized involvement and variable manifestations with a birth incidence of 1:6000. In a quarter of a century, significant progress in tuberous sclerosis complex has been made. Two responsible genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively, were discovered in the 1990s, and their functions were elucidated in the 2000s. Hamartin–Tuberin complex is involved in the phosphoinositide 3‐kinase–protein kinase B–mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex 1 activity, which is a center for various functions. Constitutive activation of mammalian target of rapamycin complex 1 causes variable manifestations in tuberous sclerosis complex. Recently, genetic tests were launched to diagnose tuberous sclerosis complex, and mammalian target of rapamycin complex 1 inhibitors are being used to treat tuberous sclerosis complex patients. As a result of these advances, new diagnostic criteria have been established and an indispensable new treatment method; that is, “a cross‐sectional medical examination system,” a system to involve many experts for tuberous sclerosis complex diagnosis and treatments, was also created. Simultaneously, the frequency of genetic tests and advances in diagnostic technology have resulted in new views on symptoms. The numbers of tuberous sclerosis complex patients without neural symptoms are increasing, and for these patients, renal manifestations and pulmonary lymphangioleiomyomatosis have become important manifestations. New concepts of tuberous sclerosis complex‐associated neuropsychiatric disorders or perivascular epithelioid cell tumors are being created. The present review contains a summary of recent advances, significant manifestations and therapy in tuberous sclerosis complex.
The functional variant rs34330 of CDKN1B is associated with risk of neuroblastoma
Authors: Capasso Mario , McDaniel Lee D. , Cimmino Flora , Cirino Andrea , Formicola Daniela , Russell Mike R. , Raman Pichai , Cole Kristina A. , Diskin Sharon J. 
Published: July 2017

AbstractThe genetic aetiology of sporadic neuroblastoma is still largely unknown. We have identified diverse neuroblastoma susceptibility loci by genomewide association studies (GWASs); however, additional SNPs that likely contribute to neuroblastoma susceptibility prompted this investigation for identification of additional variants that are likely hidden among signals discarded by the multiple testing corrections used in the analysis of genomewide data. There is evidence suggesting the CDKN1B, coding for the cycle inhibitor p27Kip1, is involved in neuroblastoma. We thus assess whether genetic variants of CDKN1B are associated with neuroblastoma. We imputed all possible genotypes across CDKN1B locus on a discovery case series of 2101 neuroblastoma patients and 4202 genetically matched controls of European ancestry. The most significantly associated rs34330 was analysed in an independent Italian cohort of 311 cases and 709 controls. In vitro functional analysis was carried out in HEK293T and in neuroblastoma cell line SHEP‐2, both transfected with pGL3‐CDKN1B‐CC or pGL3‐CDKN1B‐TT constructs. We identified an association of the rs34330 T allele (‐79C/T) with the neuroblastoma risk (Pcombined = 0.002; OR = 1.17). The risk allele (T) of this single nucleotide polymorphism led to a lower transcription rate in cells transfected with a luciferase reporter driven by the polymorphic p27Kip1 promoter (P < 0.05). Three independent sets of neuroblastoma tumours carrying ‐79TT genotype showed a tendency towards lower CDKN1B mRNA levels. Our study shows that a functional variant, associated with a reduced CDKN1B gene transcription, influences neuroblastoma susceptibility.
Genotypic diversity in root‐endophytic fungi reflects efficient dispersal and environmental adaptation
Authors: Glynou Kyriaki , Ali Tahir , Kia Sevda Haghi , Thines Marco , Maciá‐Vicente Jose G. 
Published: July 2017

AbstractStudying community structure and dynamics of plant‐associated fungi is the basis for unravelling their interactions with hosts and ecosystem functions. A recent sampling revealed that only a few fungal groups, as defined by internal transcribed spacer region (ITS) sequence similarity, dominate culturable root endophytic communities of nonmycorrhizal Microthlaspi spp. plants across Europe. Strains of these fungi display a broad phenotypic and functional diversity, which suggests a genetic variability masked by ITS clustering into operational taxonomic units (OTUs). The aims of this study were to identify how genetic similarity patterns of these fungi change across environments and to evaluate their ability to disperse and adapt to ecological conditions. A first ITS‐based haplotype analysis of ten widespread OTUs mostly showed a low to moderate genotypic differentiation, with the exception of a group identified as Cadophora sp. that was highly diverse. A multilocus phylogeny based on additional genetic loci (partial translation elongation factor 1α, beta‐tubulin and actin) and amplified fragment length polymorphism profiling of 185 strains representative of the five dominant OTUs revealed a weak association of genetic differences with geography and environmental conditions, including bioclimatic and soil factors. Our findings suggest that dominant culturable root endophytic fungi have efficient dispersal capabilities, and that their distribution is little affected by environmental filtering. Other processes, such as inter‐ and intraspecific biotic interactions, may be more important for the local assembly of their communities.
C reactive protein in healthy term newborns during the first 48 hours of life
Authors: Perrone Serafina , Lotti Federica , Longini Mariangela , Rossetti Annalisa , Bindi Ilaria , Bazzini Francesco , Belvisi Elisa , Sarnacchiaro Pasquale , Scapellato Carlo , Buonocore Giuseppe 
Published: July 2017

BackgroundEarly-onset neonatal sepsis (EOS) is a serious and potentially life-threatening disease in newborns. C reactive protein (CRP) is the most used laboratory biomarker for the detection of EOS. Little is known about normal reference values of CRP during the perinatal period as several factors are able to influence it.ObjectivesTo identify an appropriate range of CRP values in healthy term newborns during the first 48 hours of life.DesignCRP determination was performed in 859 term newborns at 12, 24 and 48 hours of life. Mode of delivery, maternal vaginal culture results, intrapartum antimicrobial prophylaxis (IAP) and other perinatal variables were recorded.ResultsCRP mean values were significantly higher at 48 hours (4.10 mg/L) than at both 24 (2.30 mg/L) and 12 hours of life (0.80 mg/L). CRP levels were affected by a number of perinatal proinflammatory variables. In particular, CRP mean values were significantly higher in babies born by vaginal delivery (3.80 mg/L) and emergency caesarean section (3.60 mg/L) than in babies born by elective caesarean section (2.10 mg/L). Completed course of IAP led to lower CRP mean values (2.90 mg/L) than IAP not completed (3.80 mg/L) or not performed (4.70 mg/L).ConclusionsPostnatal age and mode of delivery significantly influence CRP values. Reliable reference values are crucial in order to obtain an adequate diagnostic accuracy.
Listening panel agreement and characteristics of lung sounds digitally recorded from children aged 1–59 months enrolled in the Pneumonia Etiology Research for Child Health (PERCH) case–control study
Authors: McCollum Eric D , Park Daniel E , Watson Nora L , Buck W Chris , Bunthi Charatdao , Devendra Akash , Ebruke Bernard E , Elhilali Mounya , Emmanouilidou Dimitra , Garcia-Prats Anthony J , Githinji Leah , Hossain Lokman , Madhi Shabir A , Moore David P , Mulindwa Justin , Olson Dan , Awori Juliet O , Vandepitte Warunee P , Verwey Charl , West James E , Knoll Maria D , O'Brien Katherine L , Feikin Daniel R , Hammitt Laura L 
Published: July 2017

IntroductionPaediatric lung sound recordings can be systematically assessed, but methodological feasibility and validity is unknown, especially from developing countries. We examined the performance of acoustically interpreting recorded paediatric lung sounds and compared sound characteristics between cases and controls.MethodsPneumonia Etiology Research for Child Health staff in six African and Asian sites recorded lung sounds with a digital stethoscope in cases and controls. Cases aged 1–59 months had WHO severe or very severe pneumonia; age-matched community controls did not. A listening panel assigned examination results of normal, crackle, wheeze, crackle and wheeze or uninterpretable, with adjudication of discordant interpretations. Classifications were recategorised into any crackle, any wheeze or abnormal (any crackle or wheeze) and primary listener agreement (first two listeners) was analysed among interpretable examinations using the prevalence-adjusted, bias-adjusted kappa (PABAK). We examined predictors of disagreement with logistic regression and compared case and control lung sounds with descriptive statistics.ResultsPrimary listeners considered 89.5% of 792 case and 92.4% of 301 control recordings interpretable. Among interpretable recordings, listeners agreed on the presence or absence of any abnormality in 74.9% (PABAK 0.50) of cases and 69.8% (PABAK 0.40) of controls, presence/absence of crackles in 70.6% (PABAK 0.41) of cases and 82.4% (PABAK 0.65) of controls and presence/absence of wheeze in 72.6% (PABAK 0.45) of cases and 73.8% (PABAK 0.48) of controls. Controls, tachypnoea,>3 uninterpretable chest positions, crying, upper airway noises and study site predicted listener disagreement. Among all interpretable examinations, 38.0% of cases and 84.9% of controls were normal (p<0.0001); wheezing was the most common sound (49.9%) in cases.ConclusionsListening panel and case–control data suggests our methodology is feasible, likely valid and that small airway inflammation is common in WHO pneumonia. Digital auscultation may be an important future pneumonia diagnostic in developing countries.