bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of FTLD: overview and what else we can expect from genetic studies
Authors: Pottier Cyril , Ravenscroft Thomas A. , Sanchez‐Contreras Monica , Rademakers Rosa 
Published: March 2016

AbstractFrontotemporal lobar degeneration (FTLD) comprises a highly heterogeneous group of disorders clinically associated with behavioral and personality changes, language impairment, and deficits in executive functioning, and pathologically associated with degeneration of frontal and temporal lobes. Some patients present with motor symptoms including amyotrophic lateral sclerosis. Genetic research over the past two decades in FTLD families led to the identification of three common FTLD genes (microtubule‐associated protein tau, progranulin, and chromosome 9 open reading frame 72) and a small number of rare FTLD genes, explaining the disease in almost all autosomal dominant FTLD families but only a minority of apparently sporadic patients or patients in whom the family history is less clear. Identification of additional FTLD (risk) genes is therefore highly anticipated, especially with the emerging use of next‐generation sequencing. Common variants in the transmembrane protein 106 B were identified as a genetic risk factor of FTLD and disease modifier in patients with known mutations. This review summarizes for each FTLD gene what we know about the type and frequency of mutations, their associated clinical and pathological features, and potential disease mechanisms. We also provide an overview of emerging disease pathways encompassing multiple FTLD genes. We further discuss how FTLD specific issues, such as disease heterogeneity, the presence of an unclear family history and the possible role of an oligogenic basis of FTLD, can pose challenges for future FTLD gene identification and risk assessment of specific variants. Finally, we highlight emerging clinical, genetic, and translational research opportunities that lie ahead.
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Genetic research led to the identification of three common FTLD genes with rare variants (MAPT, GRN, and C9orf72) and a small number of rare genes. Efforts are now ongoing, which aimed at the identification of rare variants with high risk and/or low frequency variants with intermediate effect. Common risk variants have also been identified, such as TMEM106B. This review discusses the current knowledge on FTLD genes and the emerging disease pathways encompassing multiple FTLD genes.This article is part of the Frontotemporal Dementia special issue.
Using Disability Law to expand Academic Freedom for Disabled Researchers in the United Kingdom
Authors: Kirkham Reuben , Webster Mary , Chen Ko‐Le , Vines John 
Published: March 2016

AbstractWe consider the findings of a study of the experiences of Postgraduate Researchers with Disabilities and explore how this relates to academic freedom. Drawing upon the provisions of the Public Sector Equality Duty and Indirect Discrimination within the Equality Act (2010), we note that a range of existing public policy practices, such as the operation of the REF, are likely to be in breach of these obligations. We recommend revisions to existing practice that speak more widely to the general concern of academic freedom, suggesting that a consideration of anti‐discrimination law – rather than a purely intellectually focussed agenda – represents a pragmatic means towards shaping the inclusivity of higher education policy going forwards.
An Indigenous Feminist's Take On The Ontological Turn: ‘Ontology’ Is Just Another Word For Colonialism
Authors: Todd Zoe 
Published: March 2016

AbstractIn this article, I ask how anthropology can adopt a decolonial approach that incorporates and acknowledges the critical scholarship of Indigenous thinkers whose work and labour informs many current trends in Euro‐Western scholarship, activism and socio‐political discourse. I also query how to address ongoing structural colonialism within the academy in order to ensure that marginalised voices are heard within academic discourses.
Incidence of hepatocellular carcinoma according to hepatitis B virus genotype in Alaska Native people
Authors: Ching Lance K. , Gounder Prabhu P. , Bulkow Lisa , Spradling Philip R. , Bruce Michael G. , Negus Susan , Snowball Mary , McMahon Brian J. 
Published: March 2016

AbstractBackground & AimsMost regions of the world have ≤3 co‐circulating hepatitis B virus (HBV) genotypes, which limits direct comparisons of hepatocellular carcinoma (HCC) risk among HBV‐infected persons by genotype. We evaluated HCC incidence by HBV genotype in a cohort of Alaska Native (AN) persons where five HBV genotypes (A, B, C, D, F) have been identified.MethodsOur cohort comprised AN persons with chronic HBV infection identified during 1983–2012 who consented to participate in this study. Cohort persons were offered annual hepatitis B e antigen (HBeAg) testing and semi‐annual HCC screening. We developed a logistic regression model to compare HCC risk by genotype, adjusting for age, sex, region and HBeAg status.ResultsAmong the 1235 consenting study participants, 711 (57.6%) were male, 510 (41.3%) were HBeAg positive at cohort entry and 43 (3.5%) developed HCC. The HBV genotype was known for 1142 (92.5%) persons (13.5% A, 3.9% B, 6.7% C, 56.9% D, 19.0% F). The HCC incidence/1000 person‐years of follow‐up for genotypes A, B, C, D and F was 1.3, 0, 5.5, 0.4 and 4.2 respectively. Compared with persons with HBV genotype B/D infection, the HCC risk was higher for persons with genotypes A [adjusted odds ratio (aOR): 3.9, 95% confidence interval (CI): 1.14–13.74], C (aOR: 16.3, 95% CI: 5.20–51.11) and F (aOR: 13.9, 95% CI: 5.30–36.69).ConclusionHBV genotype is independently associated with HCC risk. AN persons with genotypes A, C and F are at higher risk compared with genotypes B or D.
Coesite in suevites from the Chesapeake Bay impact structure
Authors: Jackson John C. , Horton J. Wright , Chou I‐Ming , Belkin Harvey E. 
Published: March 2016

AbstractThe occurrence of coesite in suevites from the Chesapeake Bay impact structure is confirmed within a variety of textural domains in situ by Raman spectroscopy for the first time and in mechanically separated grains by X‐ray diffraction. Microtextures of coesite identified in situ investigated under transmitted light and by scanning electron microscope reveal coesite as micrometer‐sized grains (1–3 μm) within amorphous silica of impact‐melt clasts and as submicrometer‐sized grains and polycrystalline aggregates within shocked quartz grains. Coesite‐bearing quartz grains are present both idiomorphically with original grain margins intact and as highly strained grains that underwent shock‐produced plastic deformation. Coesite commonly occurs in plastically deformed quartz grains within domains that appear brown (toasted) in transmitted light and rarely within quartz of spheroidal texture. The coesite likely developed by a mechanism of solid‐state transformation from precursor quartz. Raman spectroscopy also showed a series of unidentified peaks associated with shocked quartz grains that likely represent unidentified silica phases, possibly including a moganite‐like phase that has not previously been associated with coesite.
NapM, a new nucleoid‐associated protein, broadly regulates gene expression and affects mycobacterial resistance to anti‐tuberculosis drugs
Authors: Liu Yu , Wang Hongyang , Cui Tao , Zhou Xiling , Jia Yanxia , Zhang Hua , He Zheng‐Guo 
Published: March 2016

SummaryNucleoid‐associated proteins (NAPs) play important roles in the global organization of bacterial chromosomes. However, potential NAPs and their functions are barely characterized in mycobacteria. In this study, NapM, an alkaline protein, functions as a new NAP. NapM is conserved in all of the sequenced mycobacterial genomes, and can recognize DNA in a length‐dependent but sequence‐independent manner. It prefers AT‐rich DNA and binds to the major groove. NapM possesses a clear DNA‐bridging function, and can protect DNA from DNase I digestion. NapM globally regulates the expression of more than 150 genes and the resistance of Mycobacterium smegmatis to two anti‐tuberculosis drugs, namely, rifampicin and ethambutol. An ABC transporter operon was found to be specifically responsible for the napM‐dependent ethambutol resistance of M. smegmatis. NapM also presents a similar regulation of anti‐tuberculosis drug resistance in M. tuberculosis. These results suggest that NapM is a new member of the mycobacterial NAP family. Our findings expand the range of identified NAPs and improve the understanding on the relationship between NAPs with antibiotic resistance in mycobacteria.
L‐2,3‐diaminopropionate generates diverse metabolic stresses in Salmonella enterica
Authors: Ernst Dustin C. , Anderson Mary E. , Downs Diana M. 
Published: March 2016

SummaryUnchecked amino acid accumulation in living cells has the potential to cause stress by disrupting normal metabolic processes. Thus, many organisms have evolved degradation strategies that prevent endogenous accumulation of amino acids. L‐2,3‐diaminopropionate (Dap) is a non‐protein amino acid produced in nature where it serves as a precursor to siderophores, neurotoxins and antibiotics. Dap accumulation in Salmonella enterica was previously shown to inhibit growth by unknown mechanisms. The production of diaminopropionate ammonia‐lyase (DpaL) alleviated Dap toxicity in S. enterica by catalyzing the degradation of Dap to pyruvate and ammonia. Here, we demonstrate that Dap accumulation in S. enterica elicits a proline requirement for growth and specifically inhibits coenzyme A and isoleucine biosynthesis. Additionally, we establish that the DpaL‐dependent degradation of Dap to pyruvate proceeds through an unbound 2‐aminoacrylate (2AA) intermediate, thus contributing to 2AA stress inside the cell. The reactive intermediate deaminase, RidA, is shown to prevent 2AA damage caused by DpaL‐dependent Dap degradation by enhancing the rate of 2AA hydrolysis. The results presented herein inform our understanding of the effects Dap has on metabolism in S. enterica, and likely other organisms, and highlight the critical role played by RidA in preventing 2AA stress stemming from Dap detoxification.
Endothelial dysfunction biomarker, endothelial cell‐specific molecule‐1, and pediatric metabolic syndrome
Authors: Halici Iclal , Palabiyik Saziye Sezin , Guducu‐Tufekci Fatma , Ozbek‐Bilgin Asli , Cayir Atilla 
Published: March 2016

AbstractBackgroundThe aim of this study was to compare serum endothelial cell‐specific molecule‐1 (endocan) in pediatric patients with metabolic syndrome (MetS) and in healthy children, and to determine whether it can be used as an indicator of endothelium damage‐induced complications in pediatric MetS patients.MethodsThe study included 30 patients, aged 6–16 years, who were diagnosed with MetS. Another 30 children with no diseases were recruited as healthy controls. Endocan concentration was measured using enzyme‐linked immunosorbent assay.ResultsEndocan was increased almost threefold in the MetS group compared with the healthy group. Systolic arterial tension and diastolic arterial tension, serum triglyceride, total cholesterol, and low‐density lipoprotein cholesterol were higher, and high‐density lipoprotein cholesterol was lower, in the MetS children than in the healthy group. Fasting blood glucose (FBG), hemoglobin A1c (HBA1C), and homeostasis model assessment insulin resistance (HOMA‐IR) were also significantly increased in the children with MetS compared with the healthy group.ConclusionsSerum endocan level in pediatric MetS patients could be an important indicator of cardiovascular risk in adulthood.
Health‐related quality of life, comorbidities and mortality in pulmonary nontuberculous mycobacterial infections: A systematic review
Authors: Yeung Man Wah , Khoo Edwin , Brode Sarah K. , Jamieson Frances B. , Kamiya Hiroyuki , Kwong Jeffrey C. , Macdonald Liane , Marras Theodore K. , Morimoto Kozo , Sander Beate 
Published: March 2016

AbstractNontuberculous mycobacterial (NTM) infections are increasing in disease frequency worldwide. This systematic review examines health‐related quality of life (HRQOL), comorbidities and mortality associated with pulmonary NTM disease. We searched MEDLINE, EMBASE, CINAHL, Scopus Life Sciences, conference proceedings and Google (earliest date available to February 2015) for primary studies. Eligible studies compared populations with and without pulmonary NTM disease in high‐income jurisdictions. We excluded studies on HIV/AIDS. All languages were accepted. Two reviewers followed MOOSE and PRISMA reporting guidelines and independently appraised quality using STROBE. All studies were summarized qualitatively regardless of quality. Of 3193 citations screened, we included 17 studies mostly from Taiwan (n = 5) and the USA (n = 4). Two studies assessed HRQOL; one assessed comorbidities, 11 assessed mortality, and three assessed multiple outcomes. Populations with pulmonary NTM reported significantly worse or similar HRQOL than the general population, depending on the instruments used. Some suggested greater prevalence of having bronchiectasis (n = 2) and greater risk of developing pulmonary tuberculosis (n = 1). Most (n = 7) suggested no difference in mortality, although only one was age‐matched and gender‐matched to the general population. Four suggested NTM populations had higher mortality—two of which compared with the general population and were deemed of high quality, while two compared with non‐NTM patients from hospital. High clinical heterogeneity in study design may explain discordant results. Bias assessments and controlling for confounding were carried out poorly. No consistent trends were observed although there is suggestion of an increased health burden from respiratory diseases and increased mortality associated with pulmonary NTM disease.
Mechanics of Supplemental Drop Wire and Half‐Pin Fixation Elements in Single Ring Circular External Fixator Constructs
Authors: Lewis Ryan A. , Lewis Daniel D. , Anderson Christopher L. , Hudson Caleb C. , Coggeshall Jason D. , Iorgulescu Alex D. , Banks Scott A. 
Published: March 2016

ObjectiveEvaluate the effects of supplemental fixation elements on the mechanical properties of a single ring circular fixator construct.Study DesignIn vitro mechanical testing.Sample population: Five construct configurations (six replicates of each configuration) were used to stabilize a 1.6 cm diameter Delrin rod bone model.MethodsConstructs were assembled using 66 mm complete rings, 1.6 mm olive wires, and 3.2 mm diameter half‐pins. Construct configurations tested were a base single ring construct, constructs with 1 supplemental drop wire or constructs with 1, 2, or 3 supplemental half‐pins. Constructs were loaded in axial compression, caudocranial and mediolateral bending, and torsion. Strain was measured in individual fixation elements during axial loading.ResultsA supplemental drop wire or half‐pin significantly increased bending and torsional stiffness. The supplemental half‐pin increased caudocranial stiffness significantly more than placing a drop wire. Placing a 2nd or 3rd pin afforded significantly greater increases in construct stiffness in all modes of loading, with 3 half‐pin constructs having significantly greater axial and caudocranial stiffness than 2 half‐pin constructs. Placing a single supplemental pin induced cantilever bending resulting in angular displacement of the Delrin rod during axial loading and high strain in both the fixation wire secured distal to the ring and the pin. Supplemental half‐pins incrementally reduced strain in all fixation elements and resulted in linear displacement of the Delrin rod during axial loading.ConclusionIf using supplemental half‐pins as fixation elements, insertion of 2 or 3 pins is preferred over a single pin.
Diversity in neural firing dynamics supports both rigid and learned hippocampal sequences
Authors: Grosmark Andres D. , Buzsáki György 
Published: March 2016

Coding what is known and what is new
Do neural activity patterns during sleep reflect the replay of a novel experience or an invariant preexisting dynamic? Grosmark and Buzsáki observed that both familiar and novel aspects of learned information are replayed during synchronous bursts of activity in the hippocampus. Familiarity was encoded by fast-firing less-modifiable neurons that showed rate and sequence correlations that persisted into postlearning sleep. The novel features of an experience were represented by a different set of slowly firing and highly plastic cells.

Science
, this issue p.
1440
Pneumococcal Vaccination in High-Risk Individuals: Are We Doing It Right?
Authors: Papadatou Ioanna , Spoulou Vana 
Published: March 2016

ABSTRACT
Controversy exists regarding the optimal use of the 23-valent pneumococcal conjugate vaccine for the protection of high-risk individuals, such as children and adults with immunocompromising conditions and the elderly. The effectiveness and immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPV23) are limited in such high-risk populations compared to the healthy, with meta-analyses failing to provide robust evidence on vaccine efficacy against invasive pneumococcal disease (IPD) or pneumonia. Moreover, several studies have demonstrated a PPV23-induced state of immune tolerance or hyporesponsiveness to subsequent vaccination, where the response to revaccination does not reach the levels achieved with primary vaccination. The clinical significance of hyporesponsiveness is not yet clarified, but attenuated humoral and cellular response could lead to reduced levels of protection and increased susceptibility to pneumococcal disease. As disease epidemiology among high-risk groups shows that we are still in need of maximum serotype coverage, the optimal use of PPV23 in the context of combined conjugate/polysaccharide vaccine schedules is an important priority. In this minireview, we discuss PPV23-induced hyporesponsiveness and its implications in designing highly effective vaccination schedules for the optimal protection for high-risk individuals.
Performance Characteristics of FilmArray Respiratory Panel v1.7 for Detection of Adenovirus in a Large Cohort of Pediatric Nasopharyngeal Samples: One Test May Not Fit All
Authors: Song Eunkyung , Wang Huanyu , Salamon Doug , Jaggi Preeti , Leber Amy 
Published: March 2016

ABSTRACT
The FilmArray Respiratory Panel (RP) v1.7 assay has improved sensitivity for detection of human adenovirus (HAdV), compared to an earlier version (RP v1.6). RP v1.7 was designed for detection of species B, C, and E but may show variable detection of species A, D, and F. We sought to evaluate the clinical and analytical performance of RP v1.7 for detection of HAdV in a large pediatric cohort. Respiratory specimens obtained from a tertiary care children's hospital between February 2014 and February 2015 were tested for HAdV by RP v1.7. If the RP v1.7 results were negative for HAdV, then the specimens were reflexed to a HAdV-specific laboratory-developed PCR (LD-PCR) assay for confirmation. A subset of specimens underwent secondary confirmatory testing using another commercially available HAdV PCR assay and a molecular typing assay for species identification. Among 4,750 specimens, a total of 146 specimens (3.1%) were HAdV positive by RP v1.7. HAdV was detected by LD-PCR in an additional 220 specimens that were negative by RP v1.7. Overall, a nearly 5% increase in HAdV detection was observed when RP v1.7-negative specimens were reflexed to LD-PCR testing. RP v1.7 did not detect HAdV with either low viral burden (threshold cycle values of >30) or nonrespiratory species (species A, D, and F), as shown in both clinical and analytic data. While the level of sensitivity of RP v1.7 may be adequate for testing among otherwise healthy children, the decreased sensitivity may be problematic for immunocompromised patients, in whom low levels of HAdV in the respiratory tract may precede systemic infection and require early intervention.
A Method for Amplicon Deep Sequencing of Drug Resistance Genes in Plasmodium falciparum Clinical Isolates from India
Authors: Rao Pavitra N. , Uplekar Swapna , Kayal Sriti , Mallick Prashant K. , Bandyopadhyay Nabamita , Kale Sonal , Singh Om P. , Mohanty Akshaya , Mohanty Sanjib , Wassmer Samuel C. , Carlton Jane M. 
Published: March 2016

ABSTRACT

A major challenge to global malaria control and elimination is early detection and containment of emerging drug resistance. Next-generation sequencing (NGS) methods provide the resolution, scalability, and sensitivity required for high-throughput surveillance of molecular markers of drug resistance. We have developed an amplicon sequencing method on the Ion Torrent PGM platform for targeted resequencing of a panel of six
Plasmodium falciparum
genes implicated in resistance to first-line antimalarial therapy, including artemisinin combination therapy, chloroquine, and sulfadoxine-pyrimethamine. The protocol was optimized using 12 geographically diverse
P. falciparum
reference strains and successfully applied to multiplexed sequencing of 16 clinical isolates from India. The sequencing results from the reference strains showed 100% concordance with previously reported drug resistance-associated mutations. Single-nucleotide polymorphisms (SNPs) in clinical isolates revealed a number of known resistance-associated mutations and other nonsynonymous mutations that have not been implicated in drug resistance. SNP positions containing multiple allelic variants were used to identify three clinical samples containing mixed genotypes indicative of multiclonal infections. The amplicon sequencing protocol has been designed for the benchtop Ion Torrent PGM platform and can be operated with minimal bioinformatics infrastructure, making it ideal for use in countries that are endemic for the disease to facilitate routine large-scale surveillance of the emergence of drug resistance and to ensure continued success of the malaria treatment policy.
Role of Antifungal Susceptibility Testing in Non-Aspergillus Invasive Mold Infections
Authors: Lamoth Frédéric , Damonti Lauro , Alexander Barbara D. 
Published: March 2016

ABSTRACT

No clinical breakpoints are available to delineate antifungal drug efficacy in non-
Aspergillus
invasive mold infections (NAIMIs). In this analysis of 39 NAIMI episodes, the MIC of the first-line antifungal drug was the most important predictor of therapeutic response. For amphotericin B, an MIC of ≤0.5 μg/ml was significantly associated with better 6-week outcomes.