bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear modeling of forced magnetic reconnection in slab geometry with NIMROD
Authors: Beidler M. T. , Callen J. D. , Hegna C. C. , Sovinec C. R.
Published: May 2017

The nonlinear, extended-magnetohydrodynamic (MHD) code NIMROD is benchmarked with the theory of time-dependent forced magnetic reconnection induced by small resonant fields in slab geometry in the context of visco-resistive MHD modeling. Linear computations agree with time-asymptotic, linear theory of flow screening of externally applied fields. The inclusion of flow in nonlinear computations can result in mode penetration due to the balance between electromagnetic and viscous forces in the time-asymptotic state, which produces bifurcations from a high-slip state to a low-slip state as the external field is slowly increased. We reproduce mode penetration and unlocking transitions by employing time-dependent externally applied magnetic fields. Mode penetration and unlocking exhibit hysteresis and occur at different magnitudes of applied field. We also establish how nonlinearly determined flow screening of the resonant field is affected by the square of the magnitude of the externally applied field. These results emphasize that the inclusion of nonlinear physics is essential for accurate prediction of the reconnected field in a flowing plasma.
‘Cyber hate’ vs. ‘cyber deliberation’
Authors: Dorostkar Niku , Preisinger Alexander
Published: May 2017

Our contribution deals with an Austrian case study on racist discourse strategies in the forums of the Austrian online newspaper derStandard.at. First, we will consider forums as a communicative form characterised by specific linguistic features as well as its technical and functional design. Furthermore, we will present an analysis of the reader’s postings from a critical-discursive perspective following the discourse-historical approach, where the readers’ comments on articles on migration and language are investigated against the background of online-specific communication. Another subject of discussion will be areas of conflict between freedom of expression, deliberation and the ‘censorship’ of the forums by the editorial staff with the help of semi-automated tools for filtering out explicit racist postings. Finally, we discuss chances and risks of the investigated forums regarding discursive and social practices within democratically constituted societies and address the question which actions can be taken to improve the quality of such forums.
Characterization and gene cloning of l-xylulose reductase involved in l-arabinose catabolism from the pentose-fermenting fungus Rhizomucor pusillus
Authors: Yamasaki-Yashiki Shino , Komeda Hidenobu , Hoshino Kazuhiro , Asano Yasuhisa
Published: May 2017

l-Xylulose reductase (LXR) catalyzes the reduction of l-xylulose to xylitol in the fungal l-arabinose catabolic pathway. LXR (RpLXR) was purified from the pentose-fermenting zygomycetous fungus Rhizomucor pusillus NBRC 4578. The native RpLXR is a homotetramer composed of 29 kDa subunits and preferred NADPH as a coenzyme. The Km values were 8.71 mM for l-xylulose and 3.89 mM for dihydroxyacetone. The lxr3 (Rplxr3) gene encoding RpLXR consists of 792 bp and encodes a putative 263 amino acid protein (Mr = 28,341). The amino acid sequence of RpLXR showed high similarity to 3-oxoacyl-(acyl-carrier-protein) reductase. The Rplxr3 gene was expressed in Escherichia coli and the recombinant RpLXR exhibited properties similar to those of native RpLXR. Transcription of the Rplxr3 gene in R. pusillus NBRC 4578 was induced in the presence of l-arabinose and inhibited in the presence of d-glucose, d-xylose, and d-mannitol, indicating that RpLXR is involved in the l-arabinose catabolic pathway.
Structural feature of N-glycans of bamboo shoot glycoproteins: useful source of plant antigenic N-glycans
Authors: Tanabe Chinatsu , Furuta Kaori , Maeda Megumi , Kimura Yoshinobu
Published: May 2017

An effective method to prepare plant complex type (PCT) N-glycans in large amounts has been required to evaluate their immunological activity. In this study, we found that glycoproteins in bamboo shoots predominantly carry PCT N-glycans including the Lewis a epitope-containing ones, suggesting that bamboo shoot is an excellent source for the plant antigenic glycans to synthesize immunoactive neoglycopolymers.
Relative role of heredity or training for music perception in children
Authors: Jain Saransh , H. S. Harshan Kumar
Published: May 2017

The effect of familial inheritance and/or environment on human behaviour has long been investigated. In the area of auditory processing, researchers have demonstrated the relative role of heredity or training in music perception for children, but both the factors were seldom been investigated simultaneously. The present study aimed to identify the factors important for music perception in children. Young children (age = 5–7 years) were selected and divided into four groups. First group of children had familial inheritance of music and also received formal music training. The second and third group had either familial inheritance of music or received music training, respectively, whereas the last group had neither of the two advantages. Tests including melody mistuning detection, timbre change detection, pitch discrimination and pitch change detection were administered. Results revealed that both familial inheritance of music expertise and music training significantly improves the music perception abilities. These findings were discussed in terms of relative role of both heredity and music training in the music perception in children. This information may be helpful designing therapeutic protocol for children with auditory processing disorders and in understanding the perceptual processes underlying music perception in children.
Genetic screening revealed usher syndrome in a paediatric Chinese patient
Authors: Qu Chunyan , Liang Fenghe , Long Qin , Zhao Min , Shang Haiqiong , Fan Lynn , Wang Li , Yan Denise , Liu Xuezhong
Published: May 2017

Introduction:

Usher syndrome (USH) is the most common cause of hereditary deaf-blindness. Three clinical subtypes have been classified. USH type I is the most severe subtype characterized by congenital severe-to-profound hearing loss, retinitis pigmentosa and vestibular dysfunction.

Methods:

One family was analyzed and the analysis included the combination of a custom capture/next-generation sequencing panel of 180 known deafness gene, Sanger sequencing and bioinformatics approaches.

Results:

Compound heterozygous mutations in the MYO7A gene: a known missense mutation c.494C > T (p.Thr165Met) and a novel missense mutation c.6113G > A (p.Gly2038Glu) were identified in a proband. This Chinese hearing-impaired child was misdiagnosed as non-syndromic hearing loss which was later changed to the diagnosis of USH type I after comprehensive audiometric, vestibular and ophthalmological examinations at 9 years old.

Conclusions:

Due to the features of genetic heterogeneity and variation in clinical manifestation, molecular diagnosis and ophthalmological examinations by skilled ophthalmologists with knowledge of USH should be suggested as a routine assessment which may improve the accuracy and reliability of etiological diagnosis for hearing loss.
WASP and SCAR are evolutionarily conserved in actin-filled pseudopod-based motility
Authors: Fritz-Laylin Lillian K. , Lord Samuel J. , Mullins R. Dyche
Published: May 2017

Diverse eukaryotic cells crawl through complex environments using distinct modes of migration. To understand the underlying mechanisms and their evolutionary relationships, we must define each mode and identify its phenotypic and molecular markers. In this study, we focus on a widely dispersed migration mode characterized by dynamic actin-filled pseudopods that we call “α-motility.” Mining genomic data reveals a clear trend: only organisms with both WASP and SCAR/WAVE—activators of branched actin assembly—make actin-filled pseudopods. Although SCAR has been shown to drive pseudopod formation, WASP’s role in this process is controversial. We hypothesize that these genes collectively represent a genetic signature of α-motility because both are used for pseudopod formation. WASP depletion from human neutrophils confirms that both proteins are involved in explosive actin polymerization, pseudopod formation, and cell migration. WASP and WAVE also colocalize to dynamic signaling structures. Moreover, retention of WASP together with SCAR correctly predicts α-motility in disease-causing chytrid fungi, which we show crawl at >30 µm/min with actin-filled pseudopods. By focusing on one migration mode in many eukaryotes, we identify a genetic marker of pseudopod formation, the morphological feature of α-motility, providing evidence for a widely distributed mode of cell crawling with a single evolutionary origin.
CCQM-K103 key comparison melanine in milk powder
Authors: Li Xiuqin , Zhang Qinghe , Li Hongmei , Li Mengwan , Wong Siu-kay , Lee Foo-Wing , Kakoulides Elias , Naujaus Evaldas , Fernandes-Whaley Maria , Prevoo-Franzsen Des , Quinn Laura , Pookrod Preeyaporn , Konopelko Leonid
Published: May 2017

Under the Comité Consultatif pour la Quantité de Matière (CCQM), a key comparison, CCQM-K103, was coordinated by the National Institute of Metrology (NIM) and Government Laboratory, Hong Kong, China (GLHK). The comparison was designed to demonstrate NMIs/DIs ability to analyze traces of melamine in milk and milk powder at concentration levels resulting from requirements for food safety. Seven NMIs or DIs participated in the comparison. Final reference value (KCRV) is 0.286 mg/kg, with standard uncertainty of the median as 0.011 mg/kg (3.8 %). The k-factor for the estimation of the expanded uncertainty was chosen as k = 2.57 ( t (0.05;5) ), thus the expanded uncertainty is 0.028 mg/kg (9.8%). The degrees of equivalence with melamine in milk powder KCRV for each participant were reported. The measurement results and degrees of equivalence should be indicative of the performance of a laboratory's measurement capability for IDMS in determining mass fractions in the range from 0.1 to 5.0 mg/kg of analytes with low molar mass (range 50-300 Da) with high polarity (pKow > -2.0) in milk and milk products. Extension to other analytes and matrices should be applied with care since there is a close linkage to other relevant parameters as e.g. sample preparation procedures (liquid/liquid extraction, SPE clean-up) and analytical separation techniques (e.g., GC-MS, LC-MS/MS etc).

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Effects of substrate stiffness and actomyosin contractility on coupling between force transmission and vinculin–paxillin recruitment at single focal adhesions
Authors: Zhou Dennis W. , Lee Ted T. , Weng Shinuo , Fu Jianping , García Andrés J.
Published: May 2017

Focal adhesions (FAs) regulate force transfer between the cytoskeleton and ECM–integrin complexes. We previously showed that vinculin regulates force transmission at FAs. Vinculin residence time in FAs correlated with applied force, supporting a mechanosensitive model in which forces stabilize vinculin’s active conformation to promote force transfer. In the present study, we examined the relationship between traction force and vinculin–paxillin localization to single FAs in the context of substrate stiffness and actomyosin contractility. We found that vinculin and paxillin FA area did not correlate with traction force magnitudes at single FAs, and this was consistent across different ECM stiffness and cytoskeletal tension states. However, vinculin residence time at FAs varied linearly with applied force for stiff substrates, and this was disrupted on soft substrates and after contractility inhibition. In contrast, paxillin residence time at FAs was independent of local applied force and substrate stiffness. Paxillin recruitment and residence time at FAs, however, were dependent on cytoskeletal contractility on lower substrate stiffness values. Finally, substrate stiffness and cytoskeletal contractility regulated whether vinculin and paxillin turnover dynamics are correlated to each other at single FAs. This analysis sheds new insights on the coupling among force, substrate stiffness, and FA dynamics.
Increased lateral microtubule contact at the cell cortex is sufficient to drive mammalian spindle elongation
Authors: Guild Joshua , Ginzberg Miriam B. , Hueschen Christina L. , Mitchison Timothy J. , Dumont Sophie
Published: May 2017

The spindle is a dynamic structure that changes its architecture and size in response to biochemical and physical cues. For example, a simple physical change, cell confinement, can trigger centrosome separation and increase spindle steady-state length at metaphase. How this occurs is not understood, and is the question we pose here. We find that metaphase and anaphase spindles elongate at the same rate when confined, suggesting that similar elongation forces can be generated independent of biochemical and spindle structural differences. Furthermore, this elongation does not require bipolar spindle architecture or dynamic microtubules. Rather, confinement increases numbers of astral microtubules laterally contacting the cortex, shifting contact geometry from “end-on” to “side-on.” Astral microtubules engage cortically anchored motors along their length, as demonstrated by outward sliding and buckling after ablation-mediated release from the centrosome. We show that dynein is required for confinement-induced spindle elongation, and both chemical and physical centrosome removal demonstrate that astral microtubules are required for such spindle elongation and its maintenance. Together the data suggest that promoting lateral cortex–microtubule contacts increases dynein-mediated force generation and is sufficient to drive spindle elongation. More broadly, changes in microtubule-to-cortex contact geometry could offer a mechanism for translating changes in cell shape into dramatic intracellular remodeling.
Coriolanus
Authors: Wells Stanley
Published: May 2017

For what is believed to be his last tragedy, Shakespeare turned once again to Ancient Rome. He chose to write a political and personal drama about a great Roman warrior of the 5th century bc whose personal fate is bound up with that of his nation. Shakespeare depicts a unique, psychologically complex individual caught up in a web of difficult personal relationships that reflect basic human situations. ‘Coriolanus’ describes the play as knotty, harsh, austere, intellectually rigorous, and resolutely unlyrical, where the dialogue is leavened with humour, sometimes conscious on the part of the speakers, but no less frequently oblique and ironical.
MarDRe: efficient MapReduce-based removal of duplicate DNA reads in the cloud
Authors: Expósito Roberto R , Veiga Jorge , González-Domínguez Jorge , Touriño Juan
Published: May 2017

This article presents MarDRe, a de novo cloud-ready duplicate and near-duplicate removal tool that can process single- and paired-end reads from FASTQ/FASTA datasets. MarDRe takes advantage of the widely adopted MapReduce programming model to fully exploit Big Data technologies on cloud-based infrastructures. Written in Java to maximize cross-platform compatibility, MarDRe is built upon the open-source Apache Hadoop project, the most popular distributed computing framework for scalable Big Data processing. On a 16-node cluster deployed on the Amazon EC2 cloud platform, MarDRe is up to 8.52 times faster than a representative state-of-the-art tool.

Availability and implementation

Source code in Java and Hadoop as well as a user’s guide are freely available under the GNU GPLv3 license at http://mardre.des.udc.es.
Sixteen lessons from a 40-year quest to understand the mysterious life of the grey triggerfish
Authors: Gerlotto François
Published: May 2017

Fish stock assessments based solely on energy flow through the ecosystem are not good predictors of population dynamics. To accurately forecast the response of populations within one or more ecological regimes, consideration must be given to non-trophic mechanisms allowing interactions inside the system, and fish behaviour in response to changes in their habitats. The example of the grey triggerfish (Balistes capriscus) in West Africa shows that fisheries biology is unable to model satisfactorily the life of a fish population. The Ecosystem Approach to Fisheries improves the models but does not overcome this fundamental limitation. Data from direct observations of fish biology and behaviour must be added to the catch and environmental data to help to design energetic-cybernetic models in order to anticipate non-linear and chaotic dynamics. This requires adding data collected by fishers (e.g. underwater acoustics) to scientific data bases, conceiving environmental indicators (e.g. habitat), and using scenarios to anticipate the reactions of populations to regime shifts. It also requires a good understanding of the population structures and strategies. We developed the concept of “pelagic metapopulation” which, through comparative analysis with the jack mackerel (Trachurus murphyi), allowed us to propose a hypothesis explaining the history of the grey triggerfish population.
Antimicrobial Stewardship Lessons From Mupirocin Use and Resistance in Methicillin-Resitant Staphylococcus Aureus
Authors: Peterson Lance R. , Samia Noelle I. , Skinner Andrew M , Chopra Amit , Smith Becky
Published: May 2017

Background

The quantitative relationship between antimicrobial agent consumption and rise or fall of antibiotic resistance has rarely been studied. We began all admission surveillance testing for methicillin-resistant Staphylococcus aureus (MRSA) in August 2005 with subsequent contact isolation and decolonization using nasally applied mupirocin ointment for those colonized. In October 2012, we discontinued decolonization of medical (nonsurgical service) patients.

Methods

We conducted a retrospective study from 2007 through 2014 of 445680 patients; 35235 were assessed because of mupirocin therapy and positive test results for MRSA. We collected data on those patients receiving 2% mupirocin ointment for decolonization to determine the defined daily doses (DDDs). A nonparametric regression technique was used to quantitate the effect of mupirocin consumption on drug resistance in MRSA.

Results

Using regressive modeling, we found that, when consumption was consistently >25 DDD/1000 patient-days, there was a statistically significant increase in mupirocin resistance with a correlating positive rate of change. When consumption was ≤25 DDD/1000 patient-days, there was a statistically significant decrease in mupirocin resistance with a correlating negative rate of change. The scatter plot of fitted versus observed mupirocin resistance values showed an R2 value of 0.89—a high correlation between mupirocin use and resistance.

Conclusions

Use of the antimicrobial agent mupirocin for decolonization had a threshold of approximately 25 DDD/1000 patient-days that separated a rise and fall of resistance within the acute-care setting. This has implications for how widely mupirocin can be used for decolonization, as well as for setting consumption thresholds when prescribing antimicrobials as part of stewardship programs.
Reference-Dependent Job Search: Evidence from Hungary*
Authors: DellaVigna Stefano , Lindner Attila , Reizer Balázs , Schmieder Johannes F.
Published: May 2017

We propose a model of job search with reference-dependent preferences, with loss aversion relative to recent income (the reference point). In this model, newly unemployed individuals search hard since consumption is below their reference point. Over time, though, they get used to lower income and thus reduce their search effort. In anticipation of a benefit cut, their search effort rises again, then declines once they get accustomed to the lower postcut benefit level. The model fits the typical pattern of exit from unemployment, even with no unobserved heterogeneity. To distinguish between this and other models, we use a unique reform in the unemployment insurance (UI) benefit path. In 2005, Hungary switched from a single-step UI system to a two-step system, with overall generosity unchanged. The system generated increased hazard rates in anticipation of, and especially following, benefit cuts in ways the standard model has a hard time explaining. We estimate a model with optimal consumption, endogenous search effort, and unobserved heterogeneity. The reference-dependent model fits the hazard rates substantially better than plausible versions of the standard model, including habit formation. Our estimates indicate a slow-adjusting reference point and substantial impatience, likely reflecting present-bias.
Evaluation of Probabilistic Disease Forecasts
Authors: Hughes Gareth , Burnett Fiona J.
Published: May 2017

The statistical evaluation of probabilistic disease forecasts often involves calculation of metrics defined conditionally on disease status, such as sensitivity and specificity. However, for the purpose of disease management decision making, metrics defined conditionally on the result of the forecast—predictive values—are also important, although less frequently reported. In this context, the application of scoring rules in the evaluation of probabilistic disease forecasts is discussed. An index of separation with application in the evaluation of probabilistic disease forecasts, described in the clinical literature, is also considered and its relation to scoring rules illustrated. Scoring rules provide a principled basis for the evaluation of probabilistic forecasts used in plant disease management. In particular, the decomposition of scoring rules into interpretable components is an advantageous feature of their application in the evaluation of disease forecasts.
Mycoplasma Pneumoniae: A Cross-sectional Population-based Comparison of Disease Severity in Preschool and School-age Children
Authors: Inchley Christopher Stephen , Berg Are Stuwitz , Vahdani Benam Afsaneh , Kvissel Anne Katrine , Leegaard Truls Michael , Nakstad Britt
Published: May 2017

Background:

Mycoplasma pneumoniae causes epidemics of upper respiratory disease and pneumonia. It is thought that M. pneumoniae usually causes milder upper respiratory disease in preschool children, with a greater chance of pneumonia in school-age children. In this population-based cross-sectional study, we present evidence that severe M. pneumoniae infection is more common in preschool children than previously thought.

Methods:

During an M. pneumoniae epidemic in our area, widespread health service and public awareness lead to extensive testing for M. pneumoniae. Medical records of hospital-referred M. pneumoniae–positive children were assessed retrospectively for respiratory disease and chest radiographic results. Severe disease was defined as supplementary oxygen or fluid requirement, mechanical ventilatory support or neurologic disease. Age-specific population figures were used to calculate incidence during the study period. Those who were 0–5-year-olds were considered preschool, whereas 6–17-year-olds were considered school-aged.

Results:

Thirty-seven preschool and 55 school-age children were referred to the hospital and tested positive for M. pneumoniae. Twenty-two (60%) preschool and 23 (42%) school-age children had severe disease [incidence 56 vs. 29 per 100,000; relative risk: 1.9; 95% confidence interval (CI): 1.06–3.4; P = 0.03]. Twenty (54%) preschool and 19 (35%) school-age children had severe pneumonia (incidence 51 vs. 24 per 100,000; relative risk: 2.1; 95% CI: 1.1–3.9; P = 0.03).

Conclusions:

During an M. pneumoniae epidemic in Akershus and North Oslo in 2011–2012, preschool children infected with M. pneumoniae had significantly higher risk of severe disease, particularly severe pneumonia, when compared with school-age children. M. pneumoniae should be considered a potential pathogen in younger children with respiratory distress, particularly during an epidemic period.
T-cell Responses to HSV-1 in Persons Who Have Survived Childhood Herpes Simplex Encephalitis
Authors: Ott Mariliis , Jing Lichen , Lorenzo Lazaro , Casanova Jean-Laurent , Zhang Shen-Ying , Koelle David M.
Published: May 2017

Background:

Herpes simplex encephalitis (HSE) after primary herpes simplex virus (HSV)-1 infection can occur in children due to inborn errors of cell-intrinsic immunity in the central nervous system. Paradoxically, symptomatic mucocutaneous HSV-1 recurrences are rare survivors of childhood HSE. T-cell–acquired immunity is thought to be involved in control of recurrent mucocutaneous HSV infection. We thus tested HSV-1–specific immunity in HSE survivors.

Methods:

We obtained serum and peripheral blood mononuclear cells (PBMCs) from participants a median of 13.5 years after HSE. HSV-1 and HSV-2 IgG was detected by type-specific immunoblot. PBMCs from subjects passing quality control criteria were tested using enzyme-linked immunospot assay for CD4 interferon-γ responses with an HSV-1 lysate and for CD8 responses using pooled synthetic HSV-1 peptide CD8 T-cell epitopes. Healthy adult PBMCs were used to standardize assays and as comparators.

Results:

All participants were HSV-1 seropositive. Most (23/24) HSE survivors had human leukocyte antigen class I types matching the human leukocyte antigen restriction of the pooled peptides. We detected HSV-specific CD8 T-cell responses in 14 of 24 (58%) HSE survivors and in 9 of 9 healthy HSV-1 seropositive adults. HSV-specific CD4 T-cell responses were present in all 5 HSE subjects tested and in 8 of 9 healthy adults. Response magnitudes were overlapping between subject groups.

Conclusions:

The defects in cell-intrinsic immunity leading to failure to control primary central nervous system HSV-1 infection do not preclude the acquisition of specific immunity or the control of recurrent mucocutaneous HSV infections. The rarity and lack of severe or recurrent mucocutaneous HSV infection in survivors of childhood HSE corresponds with intact adaptive T-cell immunity.
Advancing the Science of Myocardial Recovery with Mechanical Circulatory Support: A Working Group of the National, Heart, Lung, and Blood Institute
Authors: Drakos Stavros G. , Pagani Francis D. , Lundberg Martha S. , Baldwin J. Timothy
Published: May 2017

The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts from June 2–3, 2016, in Bethesda, MD, to develop NHLBI recommendations aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). Mechanical circulatory support devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling. Research in this field could be innovative in many ways, and the Working Group specifically discussed opportunities associated with genome–phenome systems biology approaches; genetic epidemiology; bioinformatics and precision medicine at the population level; advanced imaging modalities, including molecular and metabolic imaging; and the development of minimally invasive surgical and percutaneous bioengineering approaches. These new avenues of investigations could lead to new treatments that target phylogenetically conserved pathways involved in cardiac reparative mechanisms. A central point that emerged from the NHLBI Working Group meeting was that the lessons learned from the MCS investigational setting can be extrapolated to the broader HF population. With the precedents set by the significant effect of studies of other well-controlled and tractable subsets on larger populations, such as the genetic work in both cancer and cardiovascular disease, the work to improve our understanding of cardiac recovery and resilience in MCS patients could be transformational for the greater HF population.
Magnesium Supplementation in Vitamin D Deficiency
Authors: Reddy Pramod , Edwards Linda R.
Published: May 2017

Background:

Vitamin D and magnesium (Mg) are some of the most studied topics in medicine with enormous implications for human health and disease. Majority of the adults are deficient in both vitamin D and magnesium but continue to go unrecognized by many health care professionals.

Areas of Uncertainty:

Mg and vitamin D are used by all the organs in the body, and their deficiency states may lead to several chronic medical conditions. Studies described in the literature regarding these disease associations are contradictory, and reversal of any of these conditions may not occur for several years after adequate replacement. One should consider the supplementation therapy to be preventative rather than curative at this time.

Data Sources:

PubMed search of several reported associations between vitamin D and Mg with diseases.

Results:

Vitamin D and Mg replacement therapy in elderly patients is known to reduce the nonvertebral fractures, overall mortality, and the incidence of Alzheimer dementia.

Conclusions:

Vitamin D screening assay is readily available, but the reported lower limit of the normal range is totally inadequate for disease prevention. Based on the epidemiologic studies, ∼75% of all adults worldwide have serum 25(OH)D levels of <30 ng/mL. Because of the recent increase in global awareness, vitamin D supplementation has become a common practice, but Mg deficiency still remains unaddressed. Screening for chronic magnesium deficiency is difficult because a normal serum level may still be associated with moderate to severe deficiency. To date, there is no simple and accurate laboratory test to determine the total body magnesium status in humans. Mg is essential in the metabolism of vitamin D, and taking large doses of vitamin D can induce severe depletion of Mg. Adequate magnesium supplementation should be considered as an important aspect of vitamin D therapy.
Are global hotspots of endemic richness shaped by plate tectonics?
Authors: Loïc Pellissier , Heine Christian , Albouy Camille
Published: May 2017

Singular regions of the globe harbour a disproportionally large fraction of extant biodiversity. Spatial biodiversity gradients are frequently associated to extant ecological conditions using statistical models, but more rarely to paleo-environmental conditions, especially beyond the Quaternary. On one hand the role of plate tectonics in shaping the extant diversity of lineages is supported by numerous phylogenetic and fossil evidences, and on the other hand the spatial variation of biodiversity across the globe is rarely associated to geodynamic variables. In this study, we propose that plate tectonics explain the current location of hotspots of endemic richness across the globe. As an illustration, we used paleogeographies in a model, which quantifies through time and for each cell the potential dispersal across disconnected habitat patches. Rare events of dispersal across dynamic straits of unsuitable habitats allows species colonisation and that a subsequent absence of gene flow could lead to in-situ speciation. We evaluated whether this process could pinpoint the locations of hotspots of endemic richness computed from the ranges of 181,603 species across 14 taxonomic groups. The significant congruence between the regions highlighted by the model and the endemic richness provides evidences of the contribution of plate tectonics in shaping global biodiversity gradients. Places with high tectonic complexity, predominantly located at the confluence of major lithospheric plates such as the Mediterranean basin, Central America, Madagascar and South East Asia likely provided favourable circumstances for allopatric speciation and the emergence of new species across straits. While our illustration supports the role of plate tectonics, accounting for deep time geological events in spatial models of extant biodiversity is not straightforward. Future research should develop quantitative spatial models of biodiversity including the dynamic of ancient habitats.
Spatial distribution of extensively drug-resistant tuberculosis (XDR-TB) patients in KwaZulu-Natal, South Africa
Authors: Kapwata Thandi , Morris Natashia , Gandhi Neel R. , Campbell Angela , Mthiyane Thuli , Mpangase Primrose , Nelson Kristin N. , Allana Salim , Brust James C.M. , Moodley Pravi , Mlisana Koleka , Sarita Shah N.
Published: May 2017

Background

KwaZulu-Natal province, South Africa, has among the highest burden of XDR-TB worldwide with the majority of cases occurring due to transmission. Poor access to health facilities can be a barrier to timely diagnosis and treatment of TB, which can contribute to ongoing transmission. We sought to determine the geographic distribution of XDR-TB patients and proximity to health facilities in KwaZulu-Natal.

Methods

We recruited adults and children with XDR-TB diagnosed in KwaZulu-Natal. We calculated distance and time from participants’ home to the closest hospital or clinic, as well as to the actual facility that diagnosed XDR-TB, using tools within ArcGIS Network analyst. Speed of travel was assigned to road classes based on Department of Transport regulations. Results were compared to guidelines for the provision of social facilities in South Africa: 5km to a clinic and 30km to a hospital.

Results

During 2011–2014, 1027 new XDR-TB cases were diagnosed throughout all 11 districts of KwaZulu-Natal, of whom 404 (39%) were enrolled and had geospatial data collected. Participants would have had to travel a mean distance of 2.9 km (CI 95%: 1.8-4.1) to the nearest clinic and 17.6 km (CI 95%: 11.4-23.8) to the nearest hospital. Actual distances that participants travelled to the health facility that diagnosed XDR-TB ranged from <10 km (n=143, 36%) to >50 km (n=109, 27%). The majority (77%) of participants travelled farther than the recommended distance to a clinic (5 km) and 39% travelled farther than the recommended distance to a hospital (30 km). Nearly half (46%) of participants were diagnosed at a health facility in eThekwini district, of whom, 36% resided outside the Durban metropolitan area.

Conclusions

XDR-TB cases are widely distributed throughout KwaZulu-Natal province with a denser focus in eThekwini district. Patients travelled long distances to the health facility where they were diagnosed with XDR-TB, suggesting a potential role for migration or transportation in the XDR-TB epidemic.
An efficient platform for astrocyte differentiation from human induced pluripotent stem cells
Authors: Julia TCW , Wang Minghui , Pimenova Anna A. , Bowles Kathryn R. , Hartley Brigham J. , Lacin Emre , Machlovi Saima , Abdelaal Rawan , Karch Celeste M. , Phetnani Hemali , Slesinger Paul A. , Zhang Bin , Goate Alison M. , Brennand Kristen J.
Published: May 2017

Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. Using this method, we generated hiPSC-derived astrocyte populations (hiPSC-astrocytes) from 42 NPC lines (derived from 30 individuals) with an average of ∼90% S100β-positive cells. Transcriptomic analysis demonstrated that the hiPSC-astrocytes are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our novel protocol is a reproducible, straightforward (single media) and rapid (<30 days) method to generate homogenous populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders.

ABBREVIATIONS

hiPSC

human induced pluripotent stem cell

NPC

neural progenitor cell
Fronto-Parietal Interactions with Task-Evoked Functional Connectivity During Cognitive Control
Authors: Hwang Kai , Shine James M. , D’Esposito Mark
Published: May 2017

Flexible interaction between brain regions enables neural systems to transfer and process information adaptively for goal-directed behaviors. In the current study, we investigated neural substrates that interact with task-evoked functional connectivity during cognitive control. We conducted a human fMRI study where participants selectively attended to a category of visual stimuli in the presence of competing distractors from another stimulus category. To study flexible interactions between brain regions, we performed a dynamic functional connectivity analysis to estimate temporal changes in connectivity strength between brain regions under different levels of cognitive control. Consistent with theoretical predictions, we found that cognitive control selectively enhances functional connectivity for prioritizing the processing of task-relevant information. By regressing temporal changes in connectivity strength against activity patterns elsewhere in the brain, we localized frontal and parietal regions that potentially provide top-down biasing signals for influencing, or reading information out from, task-evoked functional connectivity. Our results suggest that in addition to modulating local activity, fronto-parietal regions could also exert top-down biasing signals to influence functional connectivity between distributed brain regions.
The floral homeotic protein SEPALLATA3 recognizes target DNA sequences by shape readout involving a conserved arginine residue in the MADS-domain
Authors: Gusewski Sandra , Melzer Rainer , Rüempler Florian , Gafert Christian , Theiβen Güenter
Published: May 2017

SEPALLATA3 ofArabidopsis thalianais a MADS-domain transcription factor and a central player in flower development. MADS-domain proteins bind as dimers to AT-rich sequences termed ‘CArG-boxes’ which share the consensus 5’-CC(A/T)6GG-3’. Since only a fraction of the abundant CArG-boxes in theArabidopsisgenome are bound by SEPALLATA3, more elaborate principles have to be discovered to better understand which features turn CArG-box sequences into genuine recognition sites. Here, we investigated to which extent the shape of the DNA contributes to the DNA-binding specificity of SEPALLATA3. We determinedin vitrobinding affinities of SEPALLATA3 to a variety of DNA probes which all contain the CArG-box motif, but differ in their DNA shape characteristics. We found that binding affinity correlates well with certain DNA shape features associated with ‘A-tracts’. Analysis of SEPALLATA3 proteins with single amino acid substitutions in the DNA-binding MADS-domain further revealed that a highly conserved arginine residue, which is expected to contact the DNA minor groove, contributes significantly to the shape readout. Our studies show that the specific recognition ofcis-regulatory elements by plant MADS-domain transcription factors heavily depend on shape readout mechanisms and that the absence of a critical arginine residue in the MADS-domain impairs binding specificity.
A critical re-evaluation of multilocus sequence typing (MLST) efforts inWolbachia
Authors: Bleidorn Christoph , Gerth Michael
Published: May 2017

Wolbachia(Alphaproteobacteria, Rickettsiales) is the most common, and arguably one of the most important inherited symbionts. Molecular differentiation ofWolbachiastrains is routinely performed with a set of five multilocus sequence typing (MLST) markers. However, since its inception in 2006, the performance of MLST inWolbachiastrain typing has not been assessed objectively. Here, we evaluate the properties ofWolbachiaMLST markers and compare it to 252 other single copy loci present in the genome of mostWolbachiastrains. Specifically, we investigated how well MLST performs at strain differentiation, at reflecting genetic diversity of strains, and as phylogenetic marker. We find that MLST loci are outperformed by other loci at all tasks they are currently employed for, and thus that they do not reflect the properties of aWolbachiastrain very well. We argue that whole genome typing approaches should be used forWolbachiatyping in the future. Alternatively, if few-loci-approaches are necessary, we provide a characterization of 252 single copy loci for a number a criteria, which may assist in designing specific typing systems or phylogenetic studies.
ATR is required to complete meiotic recombination in mice
Authors: Pacheco Sarai , Maldonado-Linares Andros , Marcet-Ortega Marina , Rojas Cristina , Martínez-Marchal Ana , Fuentes-Lazaro Judit , Lange Julian , Jasin Maria , Keeney Scott , Fernández-Capetillo Oscar , Garcia-Caldès Montserrat , Roig Ignasi
Published: May 2017

Precise execution of recombination during meiosis is essential for forming chromosomally balanced gametes. Meiotic recombination initiates with the formation and resection of DNA double-strand breaks (DSBs). Binding of replication protein A (RPA) at resected DSBs fosters association of RAD51 and DMC1, the primary effectors of homology search. It is well appreciated that cellular responses to meiotic DSBs are critical for efficient repair and quality control, but molecular features of these responses remain poorly understood, particularly in mammals. Here we provide evidence that the DNA damage response protein kinase ATR is crucial for meiotic recombination and completion of meiotic prophase in mice. Using a hypomorphicAtrmutation and pharmacological inhibition of ATRin vivoand in cultured spermatocytes, we show that ATR, through its effector kinase CHK1, promotes efficient RAD51 and DMC1 assembly at RPA-coated DSB sites and establishment of interhomolog connections during meiosis. Furthermore, our findings suggest that ATR promotes local accumulation of recombination markers on unsynapsed axes during meiotic prophase to favor homologous chromosome synapsis. These data reveal that ATR plays multiple roles in mammalian meiotic recombination.
ADAM17 is the main sheddase for the generation of human triggering receptor expressed in myeloid cells (hTREM2) ectodomain and cleaves TREM2 after histidine 157
Authors: Feuerbach Dominik , Schindler Patrick , Barske Carmen , Joller Stefanie , Beng-Louka Edwige , Worringer Katie A , Kommineni Sravya , Kaykas Ajamete , Ho Daniel J , Ye Chaoyang , Welzenbach Karl , Elain Gaelle , Klein Laurent , Brzak Irena , Mir Anis K , Farady Christopher J , Aichholz Reiner , Popp Simone , George Nathalie , Hsieh Christine L , Nakamura Mary C , Neumann Ulf
Published: May 2017

Triggering receptor expressed in myeloid cells (TREM2) is a member of the immunoglobulin superfamily and is expressed in macrophages, dendritic cells, microglia, and osteoclasts. TREM2 plays a role in phagocytosis, regulates release of cytokine, contributes to microglia maintenance, and its ectodomain is shed from the cell surface. Using both pharmacological and genetic approaches we report here that the main protease contributing to the release of TREM2 ectodomain is ADAM17, (a disintegrin and metalloproteinase domain containing protein, also called TACE, TNFα converting enzyme) while ADAM10 plays a minor role. Using mutational analysis, we demonstrate that the main cleavage site of the sheddases is located within the stalk region of TREM2 proximal to the plasma membrane. Complementary biochemical experiments reveal that cleavage occurs between histidine 157 and serine 158. Shedding is not altered for the R47H-mutated TREM2 protein that confers an increased risk for the development of Alzheimers disease. O-glycosylation is detected within the stalk region, but distant to the cleavage site. These findings reveal a link between shedding of TREM2 and its regulation during inflammatory conditions or chronic neurodegenerative disease like AD in which activity or expression of sheddases might be altered.
Model-averaged regression coefficients have a straightforward interpretation using causal conditioning
Authors: Walker Jeffrey A.
Published: May 2017

Model-averaged regression coefficients have been criticized for averaging over a set of models with parameters that have different meanings from model to model. This criticism arises because of confusion between two different parameters estimated by the coefficients of a statistical model.

Ever since Fisher, the textbook definition of a coefficient (a “differences in conditional means”) takes its meaning from probabilistic conditioning (P(Y|X)). Because the parameter estimated with probabilistic conditioning is conditional on a specific set of covariates, its meaning varies from model to model.

The coefficients in many applied statistical models, however, take their meaning from causal conditioning (P(Y|do(X))) and these coefficients estimate causal effect parameters (or simply, causal effects or Average Treatment Effects). Causal effect parameters are also differences in conditional expectations, but the event conditioned on is not the set of covariates in a statistical model but a hypothetical intervention. Because an effect parameter takes its meaning from causal and not probabilistic conditioning, it is the same from model to model, and an averaged coefficient has a straightforward interpretation as an estimate of a causal effect.

Because an effect parameter is the same from model to model, the estimates of the parameter will generally be biased. By contrast, with probabilistic conditioning, the coefficients are consistent estimates of their parameter in every model, but the parameter differs from model to model. Confounding and omitted variable bias, which are central to explanatory modeling, are meaningless in statistical modeling as mere description.

The argument developed here only addresses the “different parameters” criticism of model-averaged coefficients and is not advocating model averaging more generally.
Single molecule sequencing of M13 virus genome without amplification
Authors: Zhao Luyang , Deng Liwei , Li Gailing , Jin Huan , Cai Jinsen , Shang Huan , Li Yan , Wu Haomin , Xu Weibin , Zeng Lidong , Zhang Renli , Zhao Huan , Wu Ping , Zhou Zhiliang , Zheng Jiao , Ezanno Pierre , Yan Qin , Deem Michael , He Jiankui
Published: May 2017

Third generation sequencing is a direct measurement of DNA/RNA sequences at the single molecule level without amplification. In this study, we report sequencing of the genome of the M13 virus by a new single molecule sequencing platform. Our platform detects single molecule fluorescence by the total internal reflection microscope technique, with sequencing-by-synthesis chemistry. We sequenced the genome of M13 to a depth of 316x and 100% coverage. The consensus sequence accuracy is 100%. We demonstrated that single molecule sequencing has no significant GC bias.
Spike discharge prediction based on Neuro-fuzzy system
Authors: Zarei Mahdi
Published: May 2017

This paper presents the development and evaluation of different versions of Neuro-Fuzzy model for prediction of spike discharge patterns. We aim to predict the spike discharge variation using first spike latency and frequency-following interval. In order to study the spike discharge dynamics, we analyzed the Cerebral Cortex data of the cat from [29]. Adaptive Neuro-Fuzzy Inference Systems (ANFIS), Wang and Mendel (WM), Dynamic evolving neural-fuzzy inference system (DENFIS), Hybrid neural Fuzzy Inference System (HyFIS), genetic for lateral tuning and rule selection of linguistic fuzzy system (GFS.LT.RS) and subtractive clustering and fuzzy c-means (SBC) algorithms are applied for data. Among these algorithms, ANFIS and GFS.LT.RS models have better performance. On the other hand, ANFIS and GFS.LT.RS algorithms can be used to predict the spike discharge dynamics as a function of first spike latency and frequency with a higher accuracy compared to other algorithms.