bluuebunny/crossref_metadata_2025 huggingface dataset:
Centenarian Hotspots in Denmark
Authors: Hansen Anne Vinkel , Mortensen Laust Hvas , Westendorp Rudi
Published: August 2017

Background:

The study of regions with high prevalence of centenarians is motivated by a desire to find determinants of healthy ageing. While existing research has focused on selected candidate geographical regions, we explore the existence of hotspots in the whole the Denmark, which is a small and homogeneous country.

Methods:

We performed a Kulldorff spatial scan across the whole of Denmark, searching for regions of birth, and regions of residence at age 71, where a significantly increased percentage of the cohort born 1906-1915 became centenarians. Next we compared mortality hazards for the identified regions to the rest of the country by sex and residence at age 71.

Results:

We found a birth hotspot of 222 centenarians, 1.37 times more than the expected number, centered on a group of fairly remote rural islands. Significantly lower mortality hazards from age 71 onwards were confined to those who were born within the hotspot and persisted over a period of at least 30 years. At age 71, we found two residence-based hotspots of 348 respectively 238 centenarians, equaling 1.46- and 1.44 times the expected number. One is located in the high-income suburbs of the Danish capital and here the lower mortality hazard was confined to those who moved into the hotspot. In the second residence-based hotspot, both those who were born, and those who moved into the hotspot, showed significant lower mortality hazards.

Conclusion:

Within the whole of Denmark, we identified several centenarian hotspots that have different biological underpinnings. These outcomes point to complex gene-environmental interactions explaining a variety of longevity trajectories.
Targeting Vaccinations for the Licensed Dengue Vaccine: Considerations for Serosurvey Design
Authors: Imai N , Ferguson NM
Published: August 2017

Objective

WHO recommends countries consider dengue vaccination in geographic settings only where epidemiological data indicate a high burden of disease. In defining target populations, WHO recommend that prior infection with any dengue serotype should be >70% seroprevalence. Here we address considerations for serosurvey design in the context of the newly licensed CYD-TDV vaccine.

Methods

To explore how the design of seroprevalence surveys (age range, survey size) would affect estimates of the force of infection, for every combination of age range, total survey size, transmission setting, and test sensitivity/specificity, 100 age-specific seroprevalence surveys were simulated using a beta-binomial distribution and a simple catalytic model. The transmission intensity was then re-estimated using a Metropolis-Hastings Markov Chain Monte-Carlo algorithm.

Findings

Sampling from a wide age range led to more accurate estimates than having a larger sample size. This finding was consistent across all transmission settings. The optimal age range to sample from differed by transmission intensity, with younger and older ages being important in high and low transmission settings respectively. The optimum test sensitivity and specificity given an imperfect test also differed by transmission setting with high sensitivity being important in high transmission settings and high specificity important in low transmission settings.

Conclusions

When assessing the suitability for vaccination by seroprevalence surveys, countries should ensure that an appropriate age range is sampled, taking into account epidemiological evidence about the local burden of dengue.
Regulation of mesenchymal stem cell function by TGFβ-1 on mast cell extracellular vesicles – role of endosomal retention
Authors: Yin Yanan , Shelke Ganesh Vilas , Jang Su Chul , Lässer Cecilia , Wennmalm Stefan , Hoffmann Hans Jürgen , Nilsson Jonas , Li Li , Gho Yong Song , Lötvall Jan
Published: August 2017

Extracellular vesicles (EVs) convey biological messages between cells, either by surface-to-surface interaction, or by shuttling of bioactive molecules to a recipient cell cytoplasm. Here we show that EVs released by human primary mast cells or transformed human mast cells (HMC1), carry TGFβ-1 on their surface. EV-associated TGFβ-1 enhance the migratory activity of human mesenchymal stem cells (MSCs) compared to free TGFβ-1, as both knockdown of TGFβ, or a TGFβ-antibody, attenuate the effect. The MSCs respond by increasing matrix metalloproteinase-2 and −9 (MMP) activity. Further, EVs given to MSCs are retained in the endosomal compartments at a time of biological function, prolonging EV-associated TGFβ-1 signaling vs free TGFβ-1. When exposed to EVs, MSCs home more toward allergen-exposed lung in a mouse allergen model, resulting in attenuated allergic inflammation. Our results show that mast cell-EVs are decorated with TGFb-1, are retained in endosomes, which influences both MSC phenotype and function.
Capture-based DNA methylation sequencing facilitates diagnosis and reveals potential pathogenic mechanisms in teratogenic diabetes exposure
Authors: Schulze Katharina V. , Bhatt Amit , Azamian Mahshid S. , Sundgren Nathan C. , Zapata Gladys , Hernandez Patricia , Fox Karin , Kaiser Jeffrey R. , Belmont John W. , Hanchard Neil A.
Published: August 2017

Diabetic embryopathy (DE) describes a spectrum of birth defects associated with a teratogenic exposure to maternal diabetesin utero.These defects strongly overlap the phenotypes of known genetic syndromes; however, the pathogenic mechanisms underlying DE remain uncertain and there are no definitive tests that distinguish the diagnosis. Here, we explore the potential of DNA methylation as both a diagnostic biomarker and a means of informing disease pathogenesis in DE. Capture-based bisulfite sequencing was used to compare patterns of DNA methylation at 2,800,516 sites genome-wide in seven DE neonates and 11 healthy neonates, including five within uterodiabetes exposure. DE infants had significantly lower global DNA methylation (ANOVA, Tukey HSDp=0.045) than diabetes-unexposed, healthy controls (UH), with multiple sites showing large (mean methylation difference = 16.6%) and significant (p<0.001) differential methylation between the two groups. We found that a subset of 237 highly differentially methylated loci could accurately distinguish DE infants from both UH and diabetes-exposed healthy infants (sensitivity 80% -100%). Differentially methylated sites were enriched in intergenic (p<3.52×10-15) and intronic (p<0.001) regions found proximal to genes either associated with Mendelian syndromes that overlap the DE phenotype (e.g.TRIO,ANKRD11), or known to influence early organ development (e.g.BRAX1,RASA3). Further, by integrating information oncis-sequence variation, we found that 39.3% of loci with evidence for allele-specific methylation also showed differential methylation between DE and controls. Our study suggests a role for aberrant DNA methylation andcis-sequence variation in the pathogenesis of DE, and highlights the diagnostic potential of DNA methylation for teratogenic birth defects.
Cortical interneurons ensure maintenance of frequency tuning following adaptation
Authors: Natan Ryan G. , Rao Winnie , Geffen Maria N.
Published: August 2017

Neurons throughout the sensory pathway are tuned to specific aspects of stimuli. This selectivity is shaped by feedforward and recurrent excitatory-inhibitory interactions. In the auditory cortex (AC), two large classes of interneurons, parvalbumin- (PVs) and somatostatin- positive (SOMs) interneurons, differentially modulate frequency-dependent responses across the frequency response function of excitatory neurons. At the same time, the responsiveness of neurons in AC to sounds is dependent on the temporal context, with the majority of neurons exhibiting adaptation to repeated sounds. Here, we asked whether and how inhibitory neurons shape the frequency response function of excitatory neurons as a function of adaptation to temporal repetition of tones. The effects of suppressing both SOMs and PVs diverged for responses to preferred versus non-preferred frequencies following adaptation. Prior to adaptation, suppressing either SOM or PV inhibition drove both increases and decreases in spiking activity among cortical neurons. After adaptation, suppressing SOM activity caused predominantly disinhibitory effects, whereas suppressing PV activity still evoked bi-directional changes. SOM, but not PV-driven inhibition dynamically modulated frequency tuning as a function of adaptation. Additionally, testing across frequency tuning revealed that, unlike PVs, SOM-driven inhibition exhibited gain-like increases reflective of adaptation. Our findings suggest that distinct cortical interneurons differentially shape tuning to sensory stimuli across the neuronal receptive field, maintaining frequency selectivity of excitatory neurons during adaptation.
Very high density EEG elucidates spatiotemporal aspects of early visual processing
Authors: Robinson Amanda K , Venkatesh Praveen , Boring Matthew J. , Tarr Michael J. , Grover Pulkit , Behrmann Marlene
Published: August 2017

Standard human EEG systems based on spatial Nyquist estimates suggest that 20-30 mm electrode spacing suffices to capture neural signals on the scalp, but recent studies posit that increasing sensor density can provide higher resolution neural information. Here, we compared “super-Nyquist” density EEG (“SND”) with Nyquist density (“ND”) arrays for assessing the spatiotemporal aspects of early visual processing. EEG was measured from 128 electrodes arranged over occipitotemporal brain regions (14 mm spacing) while participants viewed flickering checkerboard stimuli. Analyses compared SND with ND-equivalent subsets of the same electrodes. Frequency-tagged stimuli were classified more accurately with SND than ND arrays in both the time and the frequency domains. Representational similarity analysis revealed that a computational model of V1 correlated more highly with the SND than the ND array. Overall, SND EEG captured more neural information from visual cortex, arguing for increased development of this approach in basic and translational neuroscience.

Abbreviations

SND

“super-Nyquist” density EEG (smaller than 20-30 mm electrode spacing)

ND

Nyquist density EEG (20-30 mm electrode spacing)
Mixed Effects Association of Single Cells Identifies an Expanded Th1-Skewed Cytotoxic Effector CD4+ T Cell Subset in Rheumatoid Arthritis
Authors: Fonseka Chamith Y. , Rao Deepak A. , Teslovich Nikola C. , Hannes Susan K. , Slowikowsi Kamil , Gurish Michael F. , Donlin Laura T. , Weinblatt Michael E. , Massarotti Elena M. , Coblyn Jonathan S. , Helfgott Simon M. , Todd Derrick J. , Bykerk Vivian P. , Karlson Elizabeth W. , Ermann Joerg , Lee Yvonne C. , Brenner Michael B. , Raychaudhuri Soumya
Published: August 2017

Abstract

High dimensional single-cell analyses have dramatically improved the ability to resolve complex mixtures of cells from human disease samples; however, identifying disease-associated cell types or cell states in patient samples remains challenging due to technical and inter-individual variation. Here we present Mixed effects modeling of Associations of Single Cells (MASC), a novel reverse single cell association strategy for testing whether case-control status influences the membership of single cells in any of multiple cellular subsets while accounting for technical confounds and biological variation. Applying MASC to mass cytometry analyses of CD4+ T cells from blood of rheumatoid arthritis (RA) patients and controls revealed a significantly expanded population of CD4+ T cells, identified as CD27- HLA-DR+ effector memory cells, in RA patients (OR = 1.7; p = 1.1 × 10−3). The frequency of CD27- HLA-DR+ cells was similarly elevated in blood samples from a second RA patient cohort, and CD27- HLA-DR+ cell frequency decreased in RA patients who respond to immunosuppressive therapy. Compared to peripheral blood, synovial fluid and synovial tissue samples from RA patients contained ∼5-fold higher frequencies of CD27- HLA-DR+ cells, which comprised ∼10% of synovial CD4+ T cells. We find that CD27- HLA-DR+ cells are abundant producers of IFN-γ and also express perforin and granzyme A at elevated levels. Thus MASC identified the expansion of a unique Th1 skewed effector T cell population with cytotoxic capacity in RA. We propose that MASC is a broadly applicable method to identify disease-associated cell populations in high-dimensional single cell data.

OneSentenceSummary

Mixed-effects regression of single cells identifies a cytotoxic Th1-like CD4+ T cell subset while accounting for inter-individual and technical variation.
Domain-General and Domain-Specific Patterns of Activity Supporting Metacognition in Human Prefrontal Cortex
Authors: Morales Jorge , Lau Hakwan , Fleming Stephen M.
Published: August 2017

Abstract

Metacognition is the capacity to evaluate the success of one’s own cognitive processes in various domains, e.g. memory and perception. It remains controversial whether metacognition relies on a domain-general resource that is applied to different tasks, or whether self-evaluative processes are domain-specific. Here we directly investigated this issue by examining the neural substrates engaged when metacognitive judgments were made by human participants during perceptual and memory tasks matched for stimulus and performance characteristics. By comparing patterns of functional magnetic resonance imaging (fMRI) activity while subjects evaluated their performance, we revealed both domain-specific and domain-general metacognitive representations. Multi-voxel activity patterns in anterior prefrontal cortex predicted levels of confidence in a domain-specific fashion, whereas domain-general signals predicting confidence and accuracy were found in a widespread network in the frontal and posterior midline. The demonstration of domain-specific metacognitive representations suggests the presence of a content-rich mechanism available to introspection and cognitive control.

Significancestatement

We use human neuroimaging to investigate processes supporting memory and perceptual metacognition. It remains controversial whether metacognition relies on a global resource that is applied to different tasks, or whether self-evaluative processes are specific to particular tasks. Using multivariate decoding methods, we provide evidence that perceptual- and memory-specific metacognitive representations cortex co-exist with generic confidence signals. Our findings reconcile previously conflicting results on the domain-specificity/generality of metacognition, and lay the groundwork for a mechanistic understanding of metacognitive judgments.
Mineral analysis of complete dog and cat foods in the UK and compliance with European guidelines
Authors: M. Davies , L. Jones , R. Alborough , C. Davis , C. Williams , D.S. Gardner
Published: August 2017

The mineral content of complete pet food is regulated to ensure health of the companion animal population. A comprehensive analysis of adherence to these regulatory guidelines has not been conducted. We measured mineral composition of a range of complete wet (n=97) and dry (n=80) canine and feline pet food sold in the UK to assess compliance with EU guidelines. While a majority of foods complied with ≥8 of 11 guidelines (99% and 83% for dry and wet food, respectively), many failed to provide nutritional minimum (e.g. Cu, 20 % of wet food) or exceeded nutritional maximum (e.g. Se, 76% of wet food). Only 6% (6/97) of wet and 39% (34/80) of dry food were fully compliant. Some foods (20-30% of all analysed) had mineral imbalances such as not having the recommended balance of Ca:P (between 1:1 to 2:1). Foods with high fish content had high levels of undesirable metal elements such as arsenic. The study highlights broad non-compliance of a range of popular pet foods sold in the UK with EU guidelines (95% and 61% of wet and dry foods, respectively). If fed exclusively and over an extended period, a number of these pet foods could impact the general health of companion animals.
Cell-free prediction of protein expression costs for growing cells
Authors: Borkowski Olivier , Bricio Carlos , Murgiano Michaela , Stan Guy-Bart , Ellis Tom
Published: August 2017

Translating heterologous proteins places significant burden on host cells, consuming expression resources leading to slower cell growth and productivity. Yet predicting the cost of protein production for any gene is a major challenge, as multiple processes and factors determine translation efficiency. Here, to enable prediction of the cost of gene expression in bacteria, we describe a standard cell-free lysate assay that determines the relationship betweenin vivoand cell-free measurements and γ, a relative measure of the resource consumption when a given protein is expressed. When combined with a computational model of translation, this enables prediction of thein vivoburden placed on growingE. colicells for a variety of proteins of different functions and lengths. Using this approach, we can predict the burden of expressing multigene operons of different designs and differentiate between the fraction of burden related to gene expression compared to action of a metabolic pathway.
Integrator Subunit 4 is a ‘Symplekin-like’ Scaffold that Associates with INTS9/11 to Form the Integrator Cleavage Module
Authors: Albrecht Todd R. , Shevtsov Sergey P. , Mascibroda Lauren G. , Peart Natoya J. , Sawyer Iain A. , Dundr Miroslav , Wagner Eric J.
Published: August 2017

Integrator (INT) is a transcriptional regulatory complex associated with RNA polymerase II that is required for the 3’-end processing of both UsnRNAs and enhancer RNAs. Integrator subunits 9 (INTS9) and INTS11 constitute the catalytic core of INT and are paralogues of the cleavage and polyadenylation specificity factors CPSF100 and CPSF73. While CPSF73/100 are known to associate with a third protein called Symplekin, there is no paralog of Symplekin within INT raising the question of how INTS9/11 associate with the other INT subunits. Here, we have identified that INTS4 is a specific and conserved interaction partner of INTS9/11 that does not interact with either subunit individually. Although INTS4 has no significant homology with Symplekin, it possesses N-terminal HEAT repeats similar to Symplekin but also contains a β-sheet rich C-terminal region, both of which are important to bind INTS9/11. We assess three functions of INT including UsnRNA 3’-end processing, maintenance of Cajal body integrity, and formation of histone locus bodies to conclude that INTS4/9/11 are the most critical of the INT subunits for UsnRNA biogenesis. Altogether, these results indicate that INTS4/9/11 compose a heterotrimeric complex that likely represents the Integrator ‘cleavage module’ responsible for its endonucleolytic activity.
Nonconsumptive predator effects on prey demography: Dogwhelk cues decrease benthic mussel recruitment
Authors: Ehlers Sonja M. , Scrosati Ricardo A. , Ellrich Julius A.
Published: August 2017

Predators have often been shown to have nonconsumptive effects (NCEs) on prey behaviour, but the demographic consequences for prey remain poorly known. This is important to understand because demography influences the impact of a species in its community. We used an intertidal predator–prey system to investigate predator NCEs on prey recruitment, a key demographic process for population persistence. Pelagic mussel larvae are known to avoid waterborne cues from dogwhelks, which prey on intertidal mussels. Through a field experiment done in Atlantic Canada, we manipulated the presence of dogwhelks in intertidal habitats during the mussel recruitment season. We measured mussel recruitment in collectors that could be reached by waterborne dogwhelk cues but not by dogwhelks themselves. We found that the nearby presence of dogwhelks significantly decreased mussel recruit density. A previous study done in the same habitats under the same experimental conditions showed that dogwhelk cues also limit the recruitment of barnacles, another prey item for dogwhelks. However, such NCEs were four times stronger than those observed for mussel recruitment. This difference relates well to the higher ability of mussels to escape predation, as mussels can relocate while barnacles cannot. Therefore, basic features of natural history may be useful to predict predator NCEs on prey recruitment.
Integrative DNA copy number detection and genotyping from sequencing and array-based platforms
Authors: Zhou Zilu , Wang Weixin , Wang Li-San , Zhang Nancy Ruonan
Published: August 2017

Motivation

Copy number variations (CNVs) are gains and losses of DNA segments and have been associated with disease. Many large-scale genetic association studies are performing CNV analysis using whole exome sequencing (WES) and whole genome sequencing (WGS). In many of these studies, previous SNP-array data are available. An integrated cross-platform analysis is expected to improve resolution and accuracy, yet there is no tool for effectively combining data from sequencing and array platforms. The detection of CNVs using sequencing data alone can also be further improved by the utilization of allele-specific reads.

Results

We propose a statistical framework, integrated Copy Number Variation detection algorithm (iCNV), which can be applied to multiple study designs: WES only, WGS only, SNP array only, or any combination of SNP and sequencing data. iCNV applies platform specific normalization, utilizes allele specific reads from sequencing and integrates matched NGS and SNP-array data by a Hidden Markov Model (HMM). We compare integrated two-platform CNV detection using iCNV to naive intersection or union of platforms and show that iCNV increases sensitivity and robustness. We also assess the accuracy of iCNV on WGS data only, and show that the utilization of allele-specific reads improve CNV detection accuracy compared to existing methods.

Availability

https://github.com/zhouzilu/iCNV

Contact

nzh@wharton.upenn.edu,zhouzilu@mail.med.upenn.edu

Supplementary information

Supplementary data are available atBioinformaticsonline.
GTP Hydrolysis by eIF5B in the Last Step of Translation Initiation Is Activated by a Rotation of the Small Ribosomal Subunit
Authors: Fernández Israel S. , Ramakrishnan V.
Published: August 2017

Placement of an initiator aminoacyl-tRNA [(f)Met-tRNAi(f)Met] base paired with the AUG initiation codon of a messenger RNA (mRNA) is the first step of translation. The eukaryotic translation factor eIF5B or its bacerial homologue IF2 facilitate the correct positioning of initiator tRNA in the P site of the ribosome. We report the electron cryomicroscopy (cryoEM) structure of a stabilized intermediate state of a yeast 80S/tRNAiMet/eIF5B complex at 3.6 Å resolution. The structure shows how a universally conserved tyrosine couples the rotational state of the small ribosomal subunit with GTP hydrolysis.
Measuring treatment outcomes in gambling disorders: a systematic review
Authors: Pickering Dylan , Keen Brittany , Entwistle Gavin , Blaszczynski Alex
Published: August 2017

Background and Aims

Considerable variation of outcome variables used to measure recovery in the gambling treatment literature has precluded effective cross‐study evaluations and hindered the development of best‐practice treatment methodologies. The aim of this systematic review was to describe current diffuse concepts of recovery in the gambling field by mapping the range of outcomes and measurement strategies used to evaluate treatments, and to identify more commonly accepted indices of recovery.

Methods

A systematic search of six academic databases for studies evaluating treatments (psychological and pharmacological) for gambling disorders with a minimum 6‐month follow‐up. Data from eligible studies were tabulated and analysis conducted using a narrative approach. Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) were adhered to.

Results

Thirty‐four studies were reviewed systematically (RCTs = 17, comparative designs = 17). Sixty‐three different outcome measures were identified: 25 (39.7%) assessed gambling‐specific constructs, 36 (57.1%) assessed non‐gambling specific constructs, and two instruments were used across both categories (3.2%). Self‐report instruments ranged from psychometrically validated to ad‐hoc author‐designed questionnaires. Units of measurement were inconsistent, particularly in the assessment of gambling behaviour. All studies assessed indices of gambling behaviour and/or symptoms of gambling disorder. Almost all studies (n = 30; 88.2%) included secondary measures relating to psychiatric comorbidities, psychological processes linked to treatment approach, or global functioning and wellbeing.

Conclusions

In research on gambling disorders, the incorporation of broader outcome domains that extend beyond disorder‐specific symptoms and behaviours suggests a multi‐dimensional conceptualization of recovery. Development of a single comprehensive scale to measure all aspects of gambling recovery could help to facilitate uniform reporting practices across the field.
Observational study shows that nurses spend more time caring for mechanically ventilated preterm infants than those receiving noninvasive ventilation
Authors: Langhammer Kristina , Sülz Sandra , Becker‐Peth Michael , Roth Bernhard
Published: August 2017

Aim

This study analysed how nursing workloads in a neonatal intensive care unit (NICU) depended on the type of respiratory support provided, and how this relationship varied by the infant's postnatal age and weight.

Methods

We used a prospective study design in a NICU in a tertiary perinatal centre in Germany. This entailed collecting data on nursing activities by observing 41 nurses for 155 hours between June 2015 and November 2015 and measuring the average nursing capacity required for direct care. Regression analysis was used to test for differences in nursing workloads between respiratory support types.

Results

Mechanically ventilated infants each required an average of 60% of the time one nurse had available to spend on direct care during the periods observed. In contrast, those receiving noninvasive ventilation only required 34% and special care infants required 13%. After the first 72 hours of life, mechanically ventilated infants required an average nursing capacity of 40%, while infants receiving noninvasive ventilation required 32% and special care infants required 25%.

Conclusion

Invasive support was associated with higher workloads than noninvasive support. The differences were partially moderated by individual factors, such as the infant's age. The findings should be replicated within a multicentre design.
Gestational diabetes care and outcomes for refugee women: a population‐based cohort study
Authors: Khan S. , Yao Z. , Shah B. R.
Published: August 2017

Aim

To determine the prevalence of adverse clinical outcomes, the rates of healthcare utilization, and the incidence of post‐partum Type 2 diabetes in refugees with gestational diabetes (GDM), compared with other immigrants and non‐immigrants.

Methods

A population‐based cohort study was conducted using healthcare databases in Ontario, Canada. Over 40 000 women with GDM having singleton live births between 2002 and 2014 were identified. We identified GDM adverse outcomes such as macrosomia, pre‐eclampsia and respiratory distress syndrome. Antenatal and newborn healthcare utilization were ascertained. Women were then followed for diagnosis of diabetes post‐partum.

Results

Both refugees and other immigrants had a lower rate than non‐immigrants of many adverse GDM outcomes, including pre‐eclampsia [relative risk (RR) 0.65, 95% confidence interval (95% CI) 0.44–0.95 and 0.61, 95% CI 0.52–0.72, respectively], preterm birth (RR 0.87, 95% CI 0.75–0.995 and 0.85, 95% CI 0.80–0.91, respectively), and respiratory distress syndrome (RR 0.83, 95% CI 0.70–0.97 and 0.78, 95% CI 0.72–0.84, respectively). However, refugees were less likely to attend well‐baby care in time for the first routine vaccination (RR 0.92, 95% CI 0.88–0.95). Incidence of post‐partum diabetes was high in all groups, but refugee women were at increased risk (hazard ratio 1.23, 95% CI 1.11–1.37).

Conclusions

Despite different circumstances leading to migration, refugees have a similar ‘healthy immigrant effect’ to other immigrants, with respect to adverse GDM outcomes. However, newborns of refugees were less likely to have well‐baby care, and refugee women were also at especially high risk of developing diabetes post‐partum. These are both important public health issues.
Effect of multiparity and ethnicity on the risk of development of diabetes: a large population‐based cohort study
Authors: Almahmeed B. , Shah B. R. , Mukerji G. , Ling V. , Booth G. L. , Feig D. S.
Published: August 2017

Aims

To investigate the relationship between increasing parity and diabetes in a large, population‐based cohort, and to examine if this relationship is different among high‐risk ethnic groups.

Methods

A population‐based, retrospective cohort study was performed in 738 440 women aged 18–50 years, who delivered babies in Ontario between 1 April 2002 and 31 March 2011. Diabetes incidence postpartum was calculated for each parity and ethnic group. A multivariable analysis of the effect of parity and ethnicity on the incidence of diabetes was performed using a Cox proportional hazards model, adjusting for confounders.

Results

The diabetes incidence rate per 1000 person‐years was 3.69 in women with 1 delivery, 4.12 in women with 3 deliveries and 7.62 in women with ≥5 deliveries. Women with ≥3 deliveries had a higher risk of developing diabetes compared with women with 1 delivery [adjusted hazard ratios 1.06 (95% CI 1.01–1.11) for 3 deliveries, 1.33 (95% CI 1.25–1.43) for 4 deliveries and 1.53 (95% CI 1.41–1.66) for ≥5 deliveries). A similar rise in risk could be seen in Chinese and South‐Asian women, with the most influence in Chinese women [hazard ratio 4.59 (95% CI 2.36–8.92) for ≥5 deliveries].

Conclusions

There was a positive and graded relationship between increasing parity and risk of development of diabetes. The influence of parity was seen in all ethnicities. This association may be partly related to increasing weight gain and retention with increasing parity, or deterioration in β‐cell function. This merits further exploration.
Influence of structure and temperature on the thermal conductivity of molten CaO–B2O3
Authors: Kim Youngjae , Yanaba Yutaka , Morita Kazuki
Published: August 2017

The effect of the temperature and borate structure on the thermal conductivity of the molten CaO–B2O3 binary system was investigated. The thermal conductivity was measured from 1573 K to approximately the liquidus temperature using a transient hot‐wire method, and was found to decrease with increasing temperature. The temperature dependence of the thermal conductivity in the molten oxide system was interpreted in terms of the lifetime of phonon‐like excitations and Maxwell relaxation times. The short‐range order borate structure was investigated through magic angle spinning (MAS) and triple‐quantum MAS (3Q‐MAS) NMR. Although the content of 4‐coordinated boron was not significantly affected by the addition of CaO, structural changes associated with the fraction of 3‐coordinated boron in ring and non‐ring sites were observed. The Raman spectra showed that the intermediate range order borate structure was changed from boroxyl rings to chain‐type metaborate units at higher CaO concentrations. The thermal conductivity decreased with decreasing BO1.5/CaO ratio, owing to the depolymerization of the borate network.
Metabolomics window into diabetic complications
Authors: Wu Tao , Qiao Shuxuan , Shi Chenze , Wang Shuya , Ji Guang
Published: August 2017

Diabetes has become a major global health problem. The elucidation of characteristic metabolic alterations during the diabetic progression is critical for better understanding its pathogenesis, and identifying potential biomarkers and drug targets. Metabolomics is a promising tool to reveal the metabolic changes and the underlying mechanism involved in the pathogenesis of diabetic complications. The present review provides an update on the application of metabolomics in diabetic complications, including diabetic coronary artery disease, diabetic nephropathy, diabetic retinopathy and diabetic neuropathy, and this review provides notes on the prevention and prediction of diabetic complications.
Evolutionary analysis of Old World arenaviruses reveals a major adaptive contribution of the viral polymerase
Authors: Pontremoli Chiara , Forni Diego , Cagliani Rachele , Pozzoli Uberto , Riva Stefania , Bravo Ignacio G. , Clerici Mario , Sironi Manuela
Published: August 2017

The Old World (OW) arenavirus complex includes several species of rodent‐borne viruses, some of which (i.e., Lassa virus, LASV and Lymphocytic choriomeningitis virus, LCMV) cause human diseases. Most LCMV and LASV infections are caused by rodent‐to‐human transmissions. Thus, viral evolution is largely determined by events that occur in the wildlife reservoirs. We used a set of human‐ and rodent‐derived viral sequences to investigate the evolutionary history underlying OW arenavirus speciation, as well as the more recent selective events that accompanied LASV spread in West Africa. We show that the viral RNA polymerase (L protein) was a major positive selection target in OW arenaviruses and during LASV out‐of‐Nigeria migration. No evidence of selection was observed for the glycoprotein, whereas positive selection acted on the nucleoprotein (NP) during LCMV speciation. Positively selected sites in L and NP are surrounded by highly conserved residues, and the bulk of the viral genome evolves under purifying selection. Several positively selected sites are likely to modulate viral replication/transcription. In both L and NP, structural features (solvent exposed surface area) are important determinants of site‐wise evolutionary rate variation. By incorporating several rodent‐derived sequences, we also performed an analysis of OW arenavirus codon adaptation to the human host. Results do not support a previously hypothesized role of codon adaptation in disease severity for non‐Nigerian strains. In conclusion, L and NP represent the major selection targets and possible determinants of disease presentation; these results suggest that field surveys and experimental studies should primarily focus on these proteins.
Random mutagenesis screen shows that Phytophthora capsici CRN83_152‐mediated cell death is not required for its virulence function(s)
Authors: Amaro Tiago M. M. M. , Thilliez Gaëtan J. A. , Mcleod Rory A. , Huitema Edgar
Published: August 2017

With the increasing availability of plant pathogen genomes, secreted proteins that aid infection (effectors) have emerged as key factors that help to govern plant–microbe interactions. The conserved CRN (CRinkling and Necrosis) effector family was first described in oomycetes by their capacity to induce host cell death. Despite recent advances towards the elucidation of CRN virulence functions, the relevance of CRN‐induced cell death remains unclear. In planta over‐expression of PcCRN83_152, a CRN effector from Phytophthora capsici, causes host cell death and boosts P. capsici virulence. We used these features to ask whether PcCRN83_152‐induced cell death is linked to its virulence function. By randomly mutating this effector, we generated PcCRN83_152 variants with no cell death (NCD) phenotypes, which were subsequently tested for activity towards enhanced virulence. We showed that a subset of PcCRN83_152 NCD variants retained their ability to boost P. capsici virulence. Moreover, NCD variants were shown to have a suppressive effect on PcCRN83_152‐mediated cell death. Our work shows that PcCRN83_152‐induced cell death and virulence function can be separated. Moreover, if these findings hold true for other cell death‐inducing CRN effectors, this work, in turn, will provide a framework for studies aimed at unveiling the virulence functions of these effectors.
On the inconsistency of pollinator species traits for predicting either response to land‐use change or functional contribution
Authors: Bartomeus Ignasi , Cariveau Daniel P. , Harrison Tina , Winfree Rachael
Published: August 2017

The response and effect trait framework, if supported empirically, would provide for powerful and general predictions about how biodiversity loss leads to loss in ecosystem function. This framework proposes that species traits will explain how different species respond to disturbance (i.e. response traits) as well as their contribution to ecosystem function (i.e. effect traits). However, predictive response and effect traits remain elusive for most systems. Here, we use data on crop pollination services provided by native, wild bees to explore the role of six commonly used species traits in determining both species’ response to land‐use change and the subsequent effect on crop pollination. Analyses were conducted in parallel for three crop systems (watermelon, cranberry, and blueberry) located within the same geographical region (mid‐Atlantic USA). Bee species traits did not strongly predict species’ response to land‐use change, and the few traits that were weakly predictive were not consistent across crops. Similarly, no trait predicted species’ overall functional contribution in any of the three crop systems, although body size was a good predictor of per capita efficiency in two systems. Overall we were unable to make generalizable predictions regarding species responses to land‐use change and its effect on the delivery of crop pollination services. Pollinator traits may be useful for understanding ecological processes in some systems, but thus far the promise of traits‐based ecology has yet to be fulfilled for pollination ecology.
Modelling the niche space of desert annuals needs to include positive interactions
Authors: Filazzola Alessandro , Sotomayor Diego A. , Lortie Christopher J.
Published: August 2017

The niche is a necessary consideration when estimating habitable area and geographic range of a species. Modellers often examine the fundamental niche and the environmental requirements for plant species, ignoring interactions among species. In deserts, positive plant interactions are important drivers of biodiversity and structure communities through many mechanistic pathways including modifying environmental conditions. Thus, we tested the hypothesis that desert shrubs increase the geographical extent of some annual species because, through modifying the microclimate, they match the niche requirements of beneficiary species. We used the database of the Global Biodiversity Information Facility to construct MaxEnt species distribution models (SDM) with and without reported benefactor species within the Mojave Desert in California. We chose 20 annual species to be modeled including 10 species that had been previously reported in the literature as being facilitated (beneficiary) and 10 that had no record of being facilitated (unreported). Beneficiary annuals co‐occurred significantly more with benefactor shrubs than the unreported annual species. The inclusion of shrubs into SDMs significantly improved model predictability and geographic range for all the beneficiary annual species, but not for the unreported annual species. Thus, positive interactions are species specific and it is possible to determine annual species dependency on benefactor shrubs at the regional scale. The co‐occurrence of benefactor shrubs and annual species can be used as a proxy for facilitation and recent developments in SDM techniques encourage the inclusion of biotic interactions. Species distribution models should include estimates of facilitation because biotic interactions determine the niche of species and can have implications with a changing climate.
Effect of ES products from Anisakis (Nematoda: Anisakidae) on experimentally induced colitis in adult zebrafish
Authors: Haarder S. , Kania P. W. , Holm T. L. , von Gersdorff Jørgensen L. , Buchmann K.
Published: August 2017

Inflammatory bowel disease (IBD) in developed countries is linked with elevated hygienic standards. One of the several factors involved in this question may be reduced exposure to the immunomodulatory effects of parasitic helminths. Several investigations on treatment of mice and humans with helminth‐derived substances have supported this notion, but underlying mechanisms remain unclear. This study therefore dissects to what extent a series of immune‐related genes are modulated in zebrafish with experimentally induced colitis following exposure to excretory‐secretory (ES) products isolated from larval Anisakis, a widely distributed fish nematode. Adult zebrafish intrarectally exposed to the colitis‐inducing agent TNBS developed severe colitis leading to 80% severe morbidity, but if co‐injected (ip) with Anisakis ES products, the morbidity rate was 50% at the end of the experiment (48 hours post‐exposure). Gene expression studies of TNBS‐treated zebrafish showed clear upregulation of a range of genes encoding inflammatory cytokines and effector molecules and some induction of genes related to the adaptive response. A distinct innate‐driven immune response was seen in both TNBS and TNBS + ES groups, but expression values were significantly depressed for several important pro‐inflammatory genes in the TNBS + ES group, indicating protective mechanisms of Anisakis ES compounds on intestinal immunopathology in zebrafish.
Usefulness of a routine endoscopic assessment of laryngeal lesions after lung cancer surgery
Authors: Fourdrain Alex , De Dominicis Florence , Iquille Jules , Lafitte Sophie , Merlusca Geoni , Witte Pfister Alejandro , Bagan Patrick , Berna Pascal
Published: August 2017

ABSTRACT

Background and objective

Laryngeal pathology following lung cancer surgery is associated with post‐operative morbidity and mortality. The aim of our study was to evaluate the usefulness of routine endoscopic assessment.

Methods

We prospectively evaluated vocal cord pathology using laryngeal endoscopy within 24 h post‐surgery. Over 25 months, 276 patients underwent thoracic surgery. We excluded 26 patients with previous laryngectomy or vocal cord paralysis, early post‐operative reintubation or patients who did not consent to an endoscopy. Endoscopic data were reported using a standardized procedure, recording vocal cord paralysis, swallowing disorders with aspiration, detected using a blue‐coloured water test and vocal cord haematoma.

Results

Among 250 patients, vocal cord paralysis was diagnosed in 13 patients (5.2%) and was associated with a higher rate of post‐operative pneumonia (P = 0.03), post‐operative bronchoscopy (P = 0.01), reintubation (P = 0.007) and a trend towards an increased 90‐day mortality rate (P = 0.09). Swallowing disorders with aspiration were diagnosed in 18 patients (7.2%) and were associated with a higher rate of post‐operative pneumonia (P = 0.007), post‐operative bronchoscopy (P = 0.01), reintubation (P = 0.004) and 90‐day mortality (P = 0.03). Vocal cord haematomas were diagnosed in 28 patients (11.2%) and were not associated with an increased post‐operative morbidity or mortality.

Conclusion

Post‐operative endoscopic laryngeal assessment is effective for diagnosing laryngeal pathology following thoracic surgery. Routine laryngeal endoscopic assessment may detect clinically silent swallowing disorders early to allow prompt treatment, which may prevent respiratory complications.
Next‐generation sequencing (NGS)‐based identification of induced mutations in a doubly mutagenized tomato (Solanum lycopersicum) population
Authors: Gupta Prateek , Reddaiah Bodanapu , Salava Hymavathi , Upadhyaya Pallawi , Tyagi Kamal , Sarma Supriya , Datta Sneha , Malhotra Bharti , Thomas Sherinmol , Sunkum Anusha , Devulapalli Sameera , Till Bradley John , Sreelakshmi Yellamaraju , Sharma Rameshwar
Published: August 2017

The identification of mutations in targeted genes has been significantly simplified by the advent of TILLING (Targeting Induced Local Lesions In Genomes), speeding up the functional genomic analysis of animals and plants. Next‐generation sequencing (NGS) is gradually replacing classical TILLING for mutation detection, as it allows the analysis of a large number of amplicons in short durations. The NGS approach was used to identify mutations in a population of Solanum lycopersicum (tomato) that was doubly mutagenized by ethylmethane sulphonate (EMS). Twenty‐five genes belonging to carotenoids and folate metabolism were PCR‐amplified and screened to identify potentially beneficial alleles. To augment efficiency, the 600‐bp amplicons were directly sequenced in a non‐overlapping manner in Illumina MiSeq, obviating the need for a fragmentation step before library preparation. A comparison of the different pooling depths revealed that heterozygous mutations could be identified up to 128‐fold pooling. An evaluation of six different software programs (camba, crisp, gatk unified genotyper, lofreq, snver and vipr) revealed that no software program was robust enough to predict mutations with high fidelity. Among these, crisp and camba predicted mutations with lower false discovery rates. The false positives were largely eliminated by considering only mutations commonly predicted by two different software programs. The screening of 23.47 Mb of tomato genome yielded 75 predicted mutations, 64 of which were confirmed by Sanger sequencing with an average mutation density of 1/367 Kb. Our results indicate that NGS combined with multiple variant detection tools can reduce false positives and significantly speed up the mutation discovery rate.
Data-Driven Sizing Specification Utilizing Consumer Text Reviews
Authors: Chaklader Rushtin , Parkinson Matthew B.
Published: August 2017

The objective of this work is to introduce a new method for determining preliminary design specifications related to human-artifact interaction. This new method uses data mining of large numbers of consumer reviews. User opinion on specific product features can be time-consuming or expensive to obtain through traditional methods including surveys, experiments, and observational studies. Data mining review text of already released products may be a potentially less time consuming and costly method. Previously established methods of determining design for human variability information from consumer reviews, such as the frequency and accuracy summation (FAS) number and subsequent manual analysis, are explored. The weighted phrase rating (WPR), a new metric which can be an automated tool to quickly analyze consumer reviews, is also introduced. It does not require manual parsing of the reviews, which extends its applicability to larger review pools. This new method is shown to quickly and economically provide information useful to the establishment of design specifications.