bluuebunny/crossref_metadata_2025 huggingface dataset:
16GT: a fast and sensitive variant caller using a 16-genotype probabilistic model
Authors: Luo Ruibang , Schatz Michael C. , Salzberg Steven L.
Published: February 2017

16GT is a variant caller for Illumina WGS and WES germline data. It uses a new 16-genotype probabilistic model to unify SNP and indel calling in a single variant calling algorithm. In benchmark comparisons with five other widely used variant callers on a modern 36-core server, 16GT ran faster and demonstrated improved sensitivity in calling SNPs, and it provided comparable sensitivity and accuracy in calling indels as compared to the GATK HaplotypeCaller.

Availability and implementation

https://github.com/aquaskyline/16GT

Contact

rluo5@jhu.edu

Supplementary information

Supplementary tables and notes are available atBioinformaticsonline.
Beyond the limitation of randomized controlled trials (RCTs)-current drug repositioning by using human induced pluripotent stem (iPS) cells technology-
Authors: Midori Okabe M.D.
Published: February 2017

To ensure the clinical value of medical interventions, randomized controlled trials (RCTs) are necessary. However, the results of conventional RCTs cannot show individual therapeutic efficacy and safety for medical intervention to a targeted patient. It is the most important weak point of conventional RCTs. Here I show that the new clinical research method by using human induced pluripotent stem (iPS) cells technology will be able to complement the most important weak point of conventional RCTs.

As the representative examples, I show the new clinical values of statins (inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase) found by using human iPS cells technology in achondroplasia or hanatophoric dysplasia (type 1) case and hepatitis C virus (HCV) infection case. Furthermore, they are also important examples for drug repositioning.

Therefore, my article would be valuable as a scientific communication for physicians and/or scientists.
Conserved changes in secondary structure and aggregation properties ofin vitroevolved proteins for thermo stability
Authors: Kundharapu Satyamurthy
Published: February 2017

Most of the screening strategies of directed evolution involved in thermo stability deals with aggregation of proteins either directly or indirectly. Here in this work I investigated what happens in aggregation property and secondary structure of the protein when it improved its thermo stability by incorporating certain amino acid changes in the protein. To study these changes I picked randomly 12 different proteins and I analyzed their 25 different thermo stable mutants. I used open access online Software to get the aggregation propensity values and values for different secondary structure elements propensities of proteins. I compared the aggregation propensity and predicted secondary structure values of thermo stable mutants with their parent Wild type proteins. The stable mutants followed three different conserved patterns to improve their thermo stability.
Modern machine learning outperforms GLMs at predicting spikes
Authors: Benjamin Ari S. , Fernandes Hugo L. , Tomlinson Tucker , Ramkumar Pavan , VerSteeg Chris , Chowdhury Raeed , Miller Lee , Kording Konrad Paul
Published: February 2017

Neuroscience has long focused on finding encoding models that effectively ask “what predicts neural spiking?” and generalized linear models (GLMs) are a typical approach. It is often unknown how much of explainable neural activity is captured, or missed, when fitting a GLM. Here we compared the predictive performance of GLMs to three leading machine learning methods: feedforward neural networks, gradient boosted trees (using XGBoost), and stacked ensembles that combine the predictions of several methods. We predicted spike counts in macaque motor (M1) and somatosensory (S1) cortices from standard representations of reaching kinematics, and in rat hippocampal cells from open field location and orientation. In general, the modern methods (particularly XGBoost and the ensemble) produced more accurate spike predictions and were less sensitive to the preprocessing of features. This discrepancy in performance suggests that standard feature sets may often relate to neural activity in a nonlinear manner not captured by GLMs. Encoding models built with machine learning techniques, which can be largely automated, more accurately predict spikes and can offer meaningful benchmarks for simpler models.
Improved LC-MS chromatographic alignment increases the accuracy of label-free quantitative proteomics: Comparison of spectral counting versus ion intensity-based proteomic quantification strategies
Authors: Ng Daniel H.J. , Humphries Jonathan D. , Selley Julian N. , Warwood Stacey , Knight David , Byron Adam , Humphries Martin J.
Published: February 2017

The ability to provide an unbiased qualitative and quantitative description of the global changes to proteins in a cell or an organism would permit the systems-wide study of complex biological systems. Label-free quantitative shotgun proteomic strategies (including LC-MS ion intensity quantification and spectral counting) are attractive because of their relatively low cost, ease of implementation, and the lack of multiplexing restrictions when comparing multiple samples. Owing to improvements in the resolution and sensitivity of mass spectrometers, and the availability of analytical software packages, protein quantification by LC-MS ion intensity has increased in popularity. Here, we have addressed the importance of chromatographic alignment on protein quantification, and then assessed how spectral counting compares to ion intensity-based proteomic quantification. Using a spiked-in protein strategy, we analysed two situations that commonly arise in the application of proteomics to cell biology: (i) samples with a small number of proteins of differential abundance in a larger non-changing background, and (ii) samples with a larger number of proteins of differential abundance. To perform these assessments on biologically relevant samples, we used isolated integrin adhesion complexes (IACs). Technical replicate analysis of isolated IACs resulted in a range of alignment scores using the Progenesis QI software package and demonstrated that higher LC-MS chromatographic alignment scores increased the precision of protein quantification. Furthermore, implementation of a simple sample batch-running strategy enabled good chromatographic alignment for hundreds of samples over multiple batches. Finally, we applied the sample batch-running strategy and compared quantification by LC-MS ion intensity to spectral counting and found that quantification by LC-MS ion intensity was more accurate and precise. In summary, these results demonstrate that chromatographic alignment is important for precise and accurate protein quantification based on LC-MS ion intensity and accordingly we present a simple sample re-ordering strategy to facilitate improved alignment. These findings are not only relevant to label-free quantification using Progenesis QI but may be useful to the wide range of MS-based quantification strategies that rely on chromatographic alignment.
α-tubulin acetylation and detyrosination correlate with starvation-induced autophagy in tobacco cells
Authors: Lytvyn Dmytro I. , Yemets Alla I. , Blume Yaroslav B.
Published: February 2017

Recent data has enabled discovery of novel functions of microtubules (MTs) in the regulation of autophagy development under physiologic/stressful conditions in yeast and animal cells. MTs participate in maturation and traffic of autophagosomes through their dynamic state changes and post-translational modifications of tubulin, including acetylation. We demonstrated the involvement of tobacco cell MTs in the development of starvation-induced autophagy via tubulin acetylation and denitrotyrosination. Induced metabolic stress caused by prolonged cultivation of BY-2 suspension cells results in glucose depletion in the culture medium and following increased rates of protein hydrolysis and autophagy. Development of autophagy was strongly accompanied by α-tubulin acetylation and detyrosination. Both post-translational modifications were caused by changes in the molecular microenvironment of the tobacco cell MTs that was revealed via Co-IP assay. The termination of autophagy led to the development of programmed cell death that was characterised by nucleosomal DNA fragmentation and decreases in α-tubulin acetylation and detyrosination. Our data suggest the role of the functional state of MTs in the mediation of plant autophagy via changes in the tubulin microenvironment and in its post-translational modifications.

SUMMARY STATEMENT

The main findings cover a possible impact of plant microtubular cytoskeleton to starvation-induced autophagy development. It can be realized by means of tubulin post-translational modifications, acetylation in the first place.
Stable association of a Drosophila-derived microbiota with its animal partner and the nutritional environment upon transfer between populations and generations
Authors: Téfit Mélisandre A. , Gillet Benjamin , Joncour Pauline , Hughes Sandrine , Leulier François
Published: February 2017

In the past years, the fruit flyDrosophila melanogasterhas been extensively used to study the relationship between animals and their associated microbes. Compared to the one of wild populations, the microbiota of laboratory-reared flies is less diverse, and comprises fewer bacterial taxa; nevertheless, the main commensal bacteria found in fly microbiota always belong to theAcetobacteraceaeandLactobacillaceaefamilies. The bacterial communities associated with the fly are environmentally acquired, and the partners engage in a perpetual re-association process. Adult flies constantly ingest and excrete microbes from and onto their feeding substrate, which are then transmitted to the next generation developing within this shared habitat. We wanted to analyze the potential changes in the bacterial community during its reciprocal transfer between the two compartments of the niche (i.e. the fly and the diet). To address this question, we used a diverse, wild-derived microbial community and analyzed its relationship with the fly population and the nutritive substrate in a given habitat. Here we show that the community was overall well maintained upon transmission to a new niche, to a new fly population and to their progeny, illustrating the stable association of a Drosophila-derived microbiota with its fly partner and the nutritional environment. These results highlight the preponderant role of the nutritional substrate in the dynamics of Drosophila/microbiota interactions, and the need to fully integrate this variable when performing such studies.
Eelgrass leaf surface microbiomes are locally variable and highly correlated with epibiotic eukaryotes
Authors: Bengtsson Mia M. , Bühler Anton , Brauer Anne , Dahlke Sven , Schubert Hendrik , Blindow Irmgard
Published: February 2017

Eelgrass(Zostera marina)is a marine foundation species essential for coastal ecosystem services around the northern hemisphere. Like all macroscopic organisms, it possesses a microbiome which may play critical roles in modulating the interaction of eelgrass with its environment. For example, its leaf surface microbiome could inhibit or attract eukaryotic epibionts which may overgrow the eelgrass leading to reduced primary productivity and subsequent eelgrass meadow decline. We used amplicon sequencing of the 16S and 18S rRNA genes of prokaryotes and eukaryotes to assess the leaf surface microbiome (prokaryotes) as well as eukaryotic epibionts in-and outside lagoons on the German Baltic Sea coast. Bacterial microbiomes varied substantially both between sites inside lagoons and between open coastal and lagoon sites. Water depth, leaf area and biofilm chlorophyllaconcentration explained a large amount of variation in both bacterial and eukaryotic community composition. Communities of bacterial and eukaryotic epibionts were highly correlated, and network analysis revealed disproportionate co-occurrence between a limited number of eukaryotic taxa and several bacterial taxa. This suggests that eelgrass leaf surface biofilms are a mosaic of the microbiomes of several eukaryotes, in addition to that of the eelgrass itself, and underlines that eukaryotic microbial diversity should be taken into account in order to explain microbiome assembly and dynamics in aquatic environments.
PGC-1α coordinates with Bcl-2 to control cell cycle in U251 cells through reducing ROS
Authors: Yao Kun , Fu Xufeng , Xing Du , Li Yan , Han Bing , Zexi Chen , Yang Shanshan , Wei Ran , Zhou Jiaqi , Cui Qinghua
Published: February 2017

B-cell lymphoma 2 (Bcl-2) has a dual function, acting both as an oncogene and an anti-tumor gene. It is well known that Bcl-2 exerts its tumor promoting function through the mitochondrial pathway. However, the mechanism by which Bcl-2 suppresses tumor formation is not well understood. We have previously shown that Bcl-2 inhibits cell cycle progression from the G0/G1to the S phase after serum starvation, and that quiescent Bcl-2 expressing cells maintained a significant lower level of mitochondrial reactive oxygen species (ROS) than the control cells. Based on the fact that ROS mediate cell cycle progression, and are controlled by peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α), a key molecule induced by prolonged starvation and involved in mitochondrial metabolism, we hypothesized that PGC-1α might be related with the cell cycle function of Bcl-2. Here, we showed that PGC-1α was upregulated upon Bcl-2 overexpression and downregulated following Bcl-2 knockdown during serum starvation. Knockdown of PGC-1α activated Bcl-2 expression. Taken together, our results suggest that after serum depletion, PGC-la might coordinate with Bcl-2 to reduce ROS, which in turn delay cell cycle progression.

Summary statement

PGC-1α coordinate with Bcl-2 delay cell cycle progression to reduce ROS after serum depletion in human glioma U251 cells.
High-throughput live-imaging of embryos in microwell arrays using a modular, inexpensive specimen mounting system
Authors: Donoughe Seth , Kim Chiyoung , Extavour Cassandra G.
Published: February 2017

Live-imaging embryos in a high-throughput manner is essential for shedding light on a wide range of questions in developmental biology, but it is difficult and costly to mount and image embryos in consistent conditions. Here, we present OMMAwell, a simple, reusable device that makes it easy to mount up to hundreds of embryos in arrays of agarose microwells with customizable dimensions and spacing. OMMAwell can be configured to mount specimens for upright or inverted microscopes, and includes a reservoir to hold live-imaging medium to maintain constant moisture and osmolarity of specimens during time-lapse imaging. All device components can be cut from a sheet of acrylic using a laser cutter. Even a novice user will be able to cut the pieces and assemble the device in less than an hour. At the time of writing, the total materials cost is less than five US dollars. We include all device design files in a commonly used format, as well as complete instructions for its fabrication and use. We demonstrate a detailed workflow for designing a custom mold and employing it to simultaneously live-image dozens of embryos at a time for more than five days, using embryos of the cricketGryllus bimaculatusas an example. Further, we include descriptions, schematics, and design files for molds that can be used with 14 additional vertebrate and invertebrate species, including most major traditional laboratory models and a number of emerging model systems. Molds have been user-tested for embryos including zebrafish (Danio rerio), fruit fly (Drosophila melanogaster), coqui frog (Eleutherodactylus coqui), annelid worm (Capitella teleta), amphipod crustacean (Parhyale hawaiensis), red flour beetle (Tribolium castaneum), and three-banded panther worm (Hofstenia miamia), as well mouse organoids (Mus musculus). Finally, we provide instructions for researchers to customize OMMAwell inserts for embryos or tissues not described herein.

Summary Statement

ThisTechniques and Resourcesarticle describes an inexpensive, customizable device for mounting and live-imaging a wide range of tissues and species; complete design files and instructions for assembly are included.
CRL2Lrr1 promotes unloading of the vertebrate replisome from chromatin during replication termination
Authors: Dewar James M. , Low Emily , Mann Matthias , Räschle Markus , Walter Johannes C.
Published: February 2017

A key event during eukaryotic replication termination is the removal of the CMG helicase from chromatin. CMG unloading involves ubiquitylation of its Mcm7 subunit and the action of the p97 ATPase. Using a proteomic screen in Xenopus egg extracts, we identified factors that are enriched on chromatin when CMG unloading is blocked. This approach identified the E3 ubiquitin ligase CRL2Lrr1, a specific p97 complex, other potential regulators of termination, and many replisome components. We show that Mcm7 ubiquitylation and CRL2Lrr1 binding to chromatin are temporally linked and occur only during replication termination. In the absence of CRL2Lrr1, Mcm7 is not ubiquitylated, CMG unloading is inhibited, and a large subcomplex of the vertebrate replisome that includes DNA Pol ε is retained on DNA. Our data identify CRL2Lrr1 as a master regulator of replisome disassembly during vertebrate DNA replication termination.
One thousand somatic SNVs per skin fibroblast cell set baseline of mosaic mutational load with patterns that suggest proliferative origin
Authors: Abyzov Alexej , Tomasini Livia , Zhou Bo , Vasmatzis Nikolaos , Coppola Gianfilippo , Amenduni Mariangela , Pattni Reenal , Wilson Michael , Gerstein Mark , Weissman Sherman , Urban Alexander E. , Vaccarino Flora M.
Published: February 2017

Few studies have been conducted to understand post-zygotic accumulation of mutations in cells of the healthy human body. We reprogrammed 32 skin fibroblast cells from families of donors into human induced pluripotent stem cell (hiPSC) lines. The clonal nature of hiPSC lines allows a high-resolution analysis of the genomes of the founder fibroblast cells without being confounded by the artifacts of single-cell whole-genome amplification. We estimate that on average a fibroblast cell in children has 1035 mostly benign mosaic SNVs. On average, 235 SNVs could be directly confirmed in the original fibroblast population by ultradeep sequencing, down to an allele frequency (AF) of 0.1%. More sensitive droplet digital PCR experiments confirmed more SNVs as mosaic with AF as low as 0.01%, suggesting that 1035 mosaic SNVs per fibroblast cell is the true average. Similar analyses in adults revealed no significant increase in the number of SNVs per cell, suggesting that a major fraction of mosaic SNVs in fibroblasts arises during development. Mosaic SNVs were distributed uniformly across the genome and were enriched in a mutational signature previously observed in cancers and in de novo variants and which, we hypothesize, is a hallmark of normal cell proliferation. Finally, AF distribution of mosaic SNVs had distinct narrow peaks, which could be a characteristic of clonal cell selection, clonal expansion, or both. These findings reveal a large degree of somatic mosaicism in healthy human tissues, link de novo and cancer mutations to somatic mosaicism, and couple somatic mosaicism with cell proliferation.
Contesting lifestyle risk and gendering coronary candidacy: lay epidemiology of heart disease in Finland in the 1970s
Authors: Jauho Mikko
Published: February 2017

This study addresses two issues currently under critical discussion in the epidemiology of cardiovascular diseases (CVD), the relative neglect of women and the individualised nature of key risk factors. It focuses on the North Karelia project (NKP), a community programme aimed at coronary heart disease (CHD) prevention in a predominantly rural Finnish region in the early 1970s, that is, during a period when the epidemiological understanding of CVD still was relatively new and actively promoted. Adopting the notions of lay epidemiology and coronary candidacy, culturally mediated explanatory models lay people use to assess who is likely to develop heart disease and why, the study shows that locals targeted by the project critically engaged with both of these bias. Based on the rich materials resulting from project activities the study shows, first, how many locals subsumed the individualised and lifestyle‐based approach to CHD prevention promoted by NKP under a more general framework emphasising the health effects of ongoing structural changes in the area, and second, how women constructed themselves as viable coronary candidates. The case supports the position in the current discussions on lay expertise that wants to integrate lay experiences more firmly into epidemiological studies and public health.
Hyperemesis gravidarum and cardiometabolic risk factors in adolescents: a follow‐up of the Northern Finland Birth Cohort 1986
Authors: Koot MH , Grooten IJ , Sebert S , Koiranen M , Järvelin MR , Kajantie E , Painter RC , Roseboom TJ
Published: February 2017

Objective

To investigate the long‐term consequences of prenatal exposure to maternal hyperemesis gravidarum upon offspring cardiometabolic risk factors.

Design

This study is part of the prospective follow‐up of the Northern Finland Birth Cohort 1986.

Setting

Between 1 July 1985 and 30 June 1986 all pregnant women in two provinces of Finland were recruited at first antenatal visit (99% of eligible participated).

Population

A total of 8953 women with liveborn singleton offspring who consented to having their children followed‐up were included.

Methods

Hyperemesis gravidarum (HG) was defined as hospitalisation during pregnancy for HG based on the International Classification of Disease (ICD) code. Women who were not hospitalised for HG during pregnancy were used as a reference group. Data on pregnancy and birth outcomes were obtained via medical records and questionnaires; 6462 adolescents, aged 16 years, underwent anthropometric measurements (HG n = 42, reference n = 6420) and 5648 adolescents had a fasting blood sample taken (HG n = 36, reference n = 5612).

Main outcome measures

Body mass index (BMI), blood pressure, fasting glucose, and lipid levels in offspring.

Results

Multivariate regression analyses showed no differences in offspring BMI (kg/m2; adjusted percentage difference HG versus reference, 2.2; 95% CI −0.1, 4.6), systolic blood pressure (adjusted difference 2.1 mmHg; 95% CI −1.5, 5.6), and fasting blood glucose (mmol/l; adjusted percentage difference, 2.3; 95% CI −0.6, 5.4), between adolescents born to mothers with and without HG.

Conclusions

We found no evidence that prenatal exposure to HG has negative consequences for cardiometabolic health of offspring at the age of 16 years.

Tweetable abstract

Hyperemesis gravidarum does not affect cardiometabolic health in adolescent offspring.
Trends in operative vaginal delivery, 2005–2013: a population‐based study
Authors: Merriam AA , Ananth CV , Wright JD , Siddiq Z , D'Alton ME , Friedman AM
Published: February 2017

Objective

The objectives of this study were to determine temporal trends in forceps and vacuum delivery and factors associated with operative vaginal delivery.

Design

Retrospective cohort.

Setting

Population‐based study of US birth records.

Population

US births from 2005 to 2013.

Methods

This study evaluated forceps and vacuum extraction during vaginal delivery in live‐born, non‐anomalous singleton gestations from ≥ 36 to < 42 weeks of gestation. The primary outcomes were vacuum, forceps and overall operative delivery. Obstetric, medical and demographic characteristics associated with operative vaginal delivery were analysed. Multivariable logistic regression models were developed to determine factors associated with forceps/vacuum use.

Results

A total of 22 598 971 vaginal deliveries between 2005 and 2013 were included in the analysis. In all, 1 083 318 (4.8%) were vacuum‐assisted and 237 792 (1.1%) were by forceps. Both vacuum and forceps deliveries decreased over the study period; vacuum deliveries decreased from 5.8% in 2005 to 4.1% in 2013, and forceps deliveries decreased from 1.4% to 0.9% during the same period. The adjusted odds ratio for forceps delivery was 0.70 (95% CI 0.69–0.72) in 2013 with 2005 as a reference. For vacuum delivery the odds ratio was 0.68 (95% CI 0.67–0.69) comparing the same years.

Conclusion

Forceps and vacuum deliveries decreased during the study period. Low rates of operative delivery pose a challenge for resident education and may limit the degree to which women have access to alternatives to caesarean delivery. Initiatives that allow future generations of obstetricians to develop expertise in performing operative deliveries in the setting of decreased volume are an urgent resident education priority.

Tweetable abstract

Forceps and vacuum delivery decreased significantly in the USA from 2005 to 2013.
Spontaneous and indicated preterm delivery risk is increased among overweight and obese women without prepregnancy chronic disease
Authors: Kim SS , Mendola P , Zhu Y , Hwang BS , Grantz KL
Published: February 2017

Objective

To investigate the independent impact of prepregnancy obesity on preterm delivery among women without chronic diseases by gestational age, preterm category and parity.

Design

A retrospective cohort study.

Setting

Data from the Consortium on Safe Labor (CSL) in the USA (2002–08).

Population

Singleton deliveries at ≥23 weeks of gestation in the CSL (43 200 nulliparas and 63 129 multiparas) with a prepregnancy body mass index (BMI) ≥18.5 kg/m2 and without chronic diseases.

Methods

Association of prepregnancy BMI and the risk of preterm delivery was examined using Poisson regression with normal weight as reference.

Main outcome measures

Preterm deliveries were categorised by gestational age (extremely, very, moderate to late) and category (spontaneous, indicated, no recorded indication).

Results

Relative risk of spontaneous preterm delivery was increased for extremely preterm among obese nulliparas (1.26, 95% CI: 0.94–1.70 for overweight; 1.88, 95% CI: 1.30–2.71 for obese class I; 1.99, 95% CI: 1.32–3.01 for obese class II/III) and decreased for moderate to late preterm delivery among overweight and obese multiparas (0.90, 95% CI: 0.83–0.97 for overweight; 0.87, 95% CI: 0.78–0.97 for obese class I; 0.79, 95% CI: 0.69–0.90 for obese class II/III). Indicated preterm delivery risk was increased with prepregnancy BMI in a dose–response manner for extremely preterm and moderate to late preterm among nulliparas, as it was for moderate to late preterm delivery among multiparas.

Conclusions

Prepregnancy BMI was associated with increased risk of preterm delivery even in the absence of chronic diseases, but the association was heterogeneous by preterm categories, gestational age and parity.

Tweetable abstract

Obese nulliparas without chronic disease had higher risk for spontaneous delivery <28 weeks of gestation.
Cruciform position for trauma resuscitation
Authors: Mitra Biswadev , Fitzgerald Mark C , Olaussen Alexander , Thaveenthiran Prasanthan , Bade‐Boon Jordan , Martin Katherine , Smit De Villiers , Cameron Peter A
Published: February 2017

Multiply injured patients represent a particularly demanding subgroup of trauma patients as they require urgent simultaneous clinical assessments using physical examination, ultrasound and invasive monitoring together with critical management, including tracheal intubation, thoracostomies and central venous access. Concurrent access to multiple body regions is essential to facilitate the concept of ‘horizontal’ resuscitation. The current positioning of trauma patient, with arms adducted, restricts this approach. Instead, the therapeutic cruciform positioning, with arms abducted at 90°, allows planning and performing of multiple life‐saving interventions simultaneously. This positioning also provides a practical surgical field with improved sterility and procedural access.
Using a butterflyfish genome as a general tool for RAD‐Seq studies in specialized reef fish
Authors: DiBattista Joseph D. , Saenz‐Agudelo Pablo , Piatek Marek J. , Wang Xin , Aranda Manuel , Berumen Michael L.
Published: February 2017

Data from a large‐scale restriction site‐associated DNA sequencing (RAD‐Seq) study of nine butterflyfish species in the Red Sea and Arabian Sea provided a means to test the utility of a recently published draft genome (Chaetodon austriacus) and assess apparent bias in this method of isolating nuclear loci. We here processed double‐digest restriction site‐associated DNA (ddRAD) sequencing data to identify single nucleotide polymorphism (SNP) markers and their associated function with and without our reference genome to see whether it improves the quality of RAD‐Seq. Our analyses indicate (i) a modest gap between the number of nonannotated versus annotated SNPs across all species, (ii) an advantage of using genomic resources for closely related but not distantly related butterflyfish species based on the ability to assign putative gene function to SNPs and (iii) an enrichment of genes among sister butterflyfish taxa related to calcium transmembrane transport and binding. The latter result highlights the potential for this approach to reveal insights into adaptive mechanisms in populations inhabiting challenging coral reef environments such as the Red Sea, Arabian Sea and Arabian Gulf with further study.
The accuracy of timed maximum local anaesthetic dose calculations with an electronic calculator, nomogram, and pen and paper
Authors: Walker J. D. , Williams N. , Williams D. J.
Published: February 2017

Forty anaesthetists calculated maximum permissible doses of eight local anaesthetic formulations for simulated patients three times with three methods: an electronic calculator; nomogram; and pen and paper. Correct dose calculations with the nomogram (85/120) were more frequent than with the calculator (71/120) or pen and paper (57/120), Bayes Factor 4 and 287, p = 0.01 and p = 0.0003, respectively. The rates of calculations at least 120% the recommended dose with each method were different, Bayes Factor 7.9, p = 0.0007: 14/120 with the calculator; 5/120 with the nomogram; 13/120 with pen and paper. The median (IQR [range]) speed of calculation with pen and paper, 38.0 (25.0–56.3 [5–142]) s, was slower than with the calculator, 24.5 (17.8–37.5 [6–204]) s, p = 0.0001, or nomogram, 23.0 (18.0–29.0 [4–100]) s, p = 1 × 10−7. Local anaesthetic dose calculations with the nomogram were more accurate than with an electronic calculator or pen and paper and were faster than with pen and paper.
Antazoline—insights into drug‐induced electrocardiographic and hemodynamic effects: Results of the ELEPHANT II substudy
Authors: Piotrowski Roman , Giebułtowicz Joanna , Baran Jakub , Sikorska Agnieszka , Gralak‐Łachowska Dagmara , Soszyńska Małgorzata , Wroczyński Piotr , Kułakowski Piotr
Published: February 2017

Background

Antazoline is an old antihistaminic and new antiarrhythmic agent with unknown mechanisms of action which recently has been shown to effectively terminate atrial fibrillation. The aim of study was to examine the effects of antazoline on hemodynamic and ECG parameters.

Methods

Antazoline was given intravenously in three 100 mg boluses to 10 healthy volunteers (four males, mean age 40 + 11 years). Hemodynamic and ECG parameters were measured using impedance cardiography [systolic (sBP), diastolic (dBP), mean (mBP) blood pressure, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and heart rate (HR), P wave, PR interval, QRS complex, QT and corrected QT (QTcF) interval]. Plasma concentration of antazoline was also measured.

Results

Antazoline caused significant prolongation of P wave, QRS as well as QT and QTcF (101 ± 10 vs 110 ± 16 ms, p < .05, and 101 ± 12 vs 107 ± 12 ms, p < .05, 399 ± 27 vs 444 ± 23 ms, p < .05, and 403 ± 21 vs 448 ± 27 ms, p < .05, respectively). Also, a significant decrease in SV was noted (94.9 ± 21.8 vs 82.4 ± 19.6 ml, p < .05). A significant correlation between changes in plasma drug concentration and changes in CO, HR, and dBP was found.

Conclusions

Antazoline impairs slightly hemodynamics, significantly reducing SV. Significant prolongation of P wave and QRS duration corresponds to drug‐induced prolongation of conduction, whereas QT prolongation represents drug‐induced prolongation of repolarization.
Use of hormone replacement therapy after risk‐reducing salpingo‐oophorectomy
Authors: Johansen Nora , Liavaag Astrid H. , Iversen Ole‐Erik , Dørum Anne , Braaten Tonje , Michelsen Trond M.
Published: February 2017

Introduction

After premenopausal risk‐reducing salpingo‐oophorectomy (RRSO) to prevent ovarian cancer, the non‐cancer‐related morbidity and mortality may be increased if sex hormones are not replaced. Several guidelines recommend systemic hormone replacement therapy (HRT) to these women until the expected age of menopause. We aimed to study the use of HRT after RRSO.

Material and methods

Participants were 324 women after RRSO and 11 160 postmenopausal controls. A subsample of 950 controls had undergone bilateral salpingo‐oophorectomy (BSO). All participants completed the same questionnaire regarding HRT use. We compared HRT use in the RRSO group with the BSO controls using logistic regression.

Results

Among the women aged ≤52 years without a history of breast cancer, 51.7% of the RRSO group and 48.7% of the BSO controls reported current use of systemic HRT (odds ratio 1.13, 95% confidence interval 0.72–1.76). Among the HRT users, systemic estrogen was used by 35.1% and 58.7% in the RRSO and BSO control groups, respectively (p = 0.001). Among the women aged >52 years, 16.8% of the RRSO group and 38.4% of the BSO controls (p < 0.001) used systemic HRT.

Conclusions

Among the RRSO women and BSO controls ≤52 years old without a history of breast cancer, relatively few were current users. If there are no contraindications, these women would benefit from systemic HRT. Additionally, almost 40% of the BSO controls >52 years used systemic HRT. Doctors should be aware of this practice and prescribe systemic HRT when indicated.
Prevalence of kidney stones in China: an ultrasonography based cross‐sectional study
Authors: Zeng Guohua , Mai Zanlin , Xia Shujie , Wang Zhiping , Zhang Keqin , Wang Li , Long Yongfu , Ma Jinxiang , Li Yi , Wan Show P. , Wu Wenqi , Liu Yongda , Cui Zelin , Zhao Zhijian , Qin Jing , Zeng Tao , Liu Yang , Duan Xiaolu , Mai Xin , Yang Zhou , Kong Zhenzhen , Zhang Tao , Cai Chao , Shao Yi , Yue Zhongjin , Li Shujing , Ding Jiandong , Tang Shan , Ye Zhangqun
Published: February 2017

Objectives

To investigate the prevalence and associated factors of kidney stones among adults in China.

Subjects and Methods

A nationwide cross‐sectional survey was conducted among individuals aged ≥18 years across China, from May 2013 to July 2014. Participants underwent urinary tract ultrasonographic examinations, completed pre‐designed and standardised questionnaires, and provided blood and urine samples for analysis. Kidney stones were defined as particles of ≥4 mm. Prevalence was defined as the proportion of participants with kidney stones and binary logistic regression was used to estimate the associated factors.

Results

A total of 12 570 individuals (45.2% men) with a mean (sd, range) age of 48.8 (15.3, 18–96) years were selected and invited to participate in the study. In all, 9310 (40.7% men) participants completed the investigation, with a response rate of 74.1%. The prevalence of kidney stones was 6.4% [95% confidence interval (CI) 5.9, 6.9], and the age‐ and sex‐adjusted prevalence was 5.8% (95% CI 5.3, 6.3; 6.5% in men and 5.1% in women). Binary logistic regression analysis showed that male gender, rural residency, age, family history of urinary stones, concurrent diabetes mellitus and hyperuricaemia, increased consumption of meat, and excessive sweating were all statistically significantly associated with a greater risk of kidney stones. By contrast, consumption of more tea, legumes, and fermented vinegar was statistically significantly associated with a lesser risk of kidney stone formation.

Conclusion

Kidney stones are common among Chinese adults, with about one in 17 adults affected currently. Some Chinese dietary habits may lower the risk of kidney stone formation.
Influence of the Laurentide Ice Sheet and relative sea‐level changes on sediment dynamics in the Estuary and Gulf of St. Lawrence since the last deglaciation
Authors: Casse Marie , Montero‐Serrano Jean‐Carlos , St‐Onge Guillaume
Published: February 2017

Physical properties, grain size, bulk mineralogy, elemental geochemistry and magnetic parameters of three sediment piston cores recovered in the Laurentian Channel from its head to its mouth were investigated to reconstruct changes in detrital sediment provenance and transport related to climate variability since the last deglaciation. The comparison of the detrital proxies indicates the succession of two sedimentary regimes in the Estuary and Gulf of St. Lawrence (EGSL) during the Holocene, which are associated with the melting history of the Laurentide Ice Sheet (LIS) and relative sea‐level changes. During the early Holocene (10–8.5 cal. kaBP), high sedimentation rates together with mineralogical, geochemical and magnetic signatures indicate that sedimentation in theEGSLwas mainly controlled by meltwater discharges from the local retreat of the southeastern margin of theLISon the Canadian Shield. At this time, sediment‐laden meltwater plumes caused the accumulation of fine‐grained sediments in the ice‐distal zones. Since the mid‐Holocene, postglacial movements of the continental crust, related to the withdrawal of theLIS(c. 6 cal. kaBP), have triggered significant variations in relative sea level (RSL) in theEGSL. The significant correlation between theRSLcurves and the mineralogical, geochemical, magnetic and grain‐size data suggest that theRSLwas the dominant force acting on the sedimentary dynamics of theEGSLduring the mid‐to‐late Holocene. Beyond 6 cal. kaBP, characteristic mineralogical, geochemical, magnetic signatures and diffuse spectral reflectance data suggest that the Canadian Maritime Provinces and western Newfoundland coast are the primary sources for detrital sediments in the Gulf of St. Lawrence, with the Canadian Shield acting as a secondary source. Conversely, in the lower St. Lawrence Estuary, detrital sediments are mainly supplied by the Canadian Shield province. Finally, our results suggest that the modern sedimentation regime in theEGSLwas established during the mid‐Holocene.
Late‐Holocene wind‐field evolution at the southern Baltic coast as revealed by GPR data from the Mrzeżyno dunefield, NW Poland
Authors: Żuk Tomasz , Sydor Paweł , Sambrook Smith Gregory H.
Published: February 2017

All dunes within a dunefield usually show a similar response to the wind regime. However, in the late‐Holocene coastal dunefield in NW Poland the surface topography suggests that slipface orientation may vary significantly with distance from the coast, which is rarely reported in the literature. The dunefield was stabilized with forest in the mid‐19th century, preserving a unique record of atmospheric circulation in the South Baltic region at the end of the Little Ice Age. To elucidate the Holocene processes occurring along the study site a pseudo‐3D GPR data set was collected. Six grids of parallel GPR lines combined with 400 m of GPR profiles (2D) were collected across the dunefield and displayed using GOCAD for interpretation and geostatistical analysis. The geophysical data revealed that the larger dunes almost entirely consist of steeply laminated facies. Most importantly the pseudo‐3D data, supported by geostatistical estimates of strata dip directions, revealed the existence of three zones parallel to the coastline with the mean dip direction almost perpendicular to the coast in the northern coastal strip and almost parallel to it in the southern part. Spreads of the dip directions in pseudo‐3D GPR data sets recorded on the stoss slopes of dunes and crests suggested initial deposition on transverse dunes, which later were transformed into barchanoid dunes. This can probably be linked to changes in the wind regime, i.e. reduction in velocity of the northern and northwestern winds leading to reduced sediment supply from the coast. While the data provide a new interpretation of Holocene dunefield dynamics at this site, they also suggest that the minimum number of pseudo‐3D GPR grids required to establish general trends using geostatistical analysis should be at least 10, with even more data needed at larger, or more complex dunefields.
The distribution and utility of sea‐level indicators in Eurasian sub‐Arctic salt marshes (White Sea, Russia)
Authors: Kemp Andrew C. , Horton Benjamin P. , Nikitina Daria , Vane Christopher H. , Potapova Marina , Weber‐Bruya Elizabeth , Culver Stephen J. , Repkina Tatyana , Hill David F.
Published: February 2017

In support of efforts to reconstruct relative sea level (RSL), we investigated the utility of foraminifera, diatoms and bulk‐sediment geochemistry (δ13C, C:N and parameters measured by Rock‐Eval pyrolysis) as sea‐level indicators in Eurasian sub‐Arctic salt marshes. At three salt marshes (<15 km apart) in Dvina Bay (White Sea, Russia), we collected surface sediment samples along transects from subtidal to Taiga forest environments. Foraminifera at all sites formed bipartite assemblages, where elevations below mean high higher water (MHHW) were dominated by Miliammina spp. and elevations between MHHW and the highest occurrence of foraminifera were dominated by Jadammina macrescens and Balticammina pseudomacrescens. Five high‐diversity groups of diatoms were identified and they displayed pronounced variability amongst the study sites. Bulk‐sediment geochemistry recognized two groups (clastic‐dominated environments below MHHW and organic‐rich environments above MHHW). As one group included subtidal elevations and the other included supratidal elevations, we conclude that the measured geochemical parameters are not stand‐alone sea‐level indicators. Core JT2012 captured a regressive sediment succession of clastic, tidal‐flat sediment overlain by salt‐marsh organic silt and freshwater peat. The salt‐marsh sediment accumulated at 2804±52 years before present and preserved foraminifera (Jadammina macrescens and Balticammina pseudomacrescens) with good analogy to modern assemblages indicating that RSL was +2.60±0.47 m at this time. Diatoms confirm that marine influence decreased through time, but the lack of analogy between modern and core assemblages limited their utility as sea‐level indicators. Geochemical parameters also indicate a reduction in marine influence through time. We conclude that RSL reconstructions derived from salt‐marsh sediment preserved beneath Eurasian sub‐Arctic peatlands can provide valuable insight into the spatio‐temporal evolution of the Fennoscandian and Eurasian ice sheets.
Review of xanthomatous lesions of the sella
Authors: Kleinschmidt‐DeMasters B.K. , Lillehei Kevin O. , Hankinson Todd C.
Published: February 2017

Xanthomatous lesions of the sellar region have traditionally been divided into two separate categories, xanthomatous hypophysitis (XH) and xanthogranuloma (XG) of the sellar region. The seminal article on XH, a condition typified by foamy histiocytes and lymphoplasmacytic infiltrates in the pituitary gland/sellar region, but usually little or no hemosiderin pigment, detailed three patients. However, most reports since that time have been single cases, making understanding of the entity difficult. In contrast, the seminal report on XG, characterized by sellar region cholesterol clefts, lymphoplasmacytic infiltrates, marked hemosiderin deposits, fibrosis, multinucleated giant cells around cholesterol clefts, eosinophilic granular necrotic debris, and accumulation of macrophages, included 37 patients, allowing more insights into etiology. Few examples could be linked to adamantinomatous craniopharyngioma, and although ciliated epithelium similar to that of Rathke cleft cyst (RCC) was identified up to 35% of the 37 cases, it could not be proven that XG was related to hemorrhage into RCC. Case reports since that time, however, occasionally linked XG to RCC when an etiology could be identified at all, and a few recognized that a spectrum exists in xanthomatous lesions of the sella. They review literature, adding 23 cases from our own experience, to confirm that overlap occurs between XH and XG, and that the majority—but not all—can be linked to RCC leakage/rupture/hemorrhage. It was suggested that progressive accumulation of hemosiderin pigment in the lesion, possibly caused by the multiple episodes of bleeding, could account for the transition of at least some cases of XH to XG.
Adiponectin improves endothelial function in mesenteric arteries of rats fed a high‐fat diet: role of perivascular adipose tissue
Authors: Sena Cristina M , Pereira Ana , Fernandes Rosa , Letra Liliana , Seiça Raquel M
Published: February 2017

Background and Purpose

Adiponectin, the most abundant peptide secreted by adipocytes, is involved in the regulation of energy metabolism and vascular physiology. Here, we have investigated the effects of exogenous administration of adiponectin on metabolism, vascular reactivity and perivascular adipose tissue (PVAT) of mesenteric arteries in Wistar rats fed a high‐fat diet.

Experimental Approach

The effects of adiponectin on NO‐dependent and independent vasorelaxation were investigated in isolated mesenteric arteries from 12‐month‐old male Wistar rats (W12m) fed a high‐fat diet (HFD) for 4 months and compared with those from age‐matched rats given a control diet. Adiponectin ((96 μg·day−1) was administered by continuous infusion with a minipump, implanted subcutaneously, for 28 days.

Key Results

Chronic adiponectin treatment reduced body weight, total cholesterol, free fatty acids, fasting glucose and area under the curve of intraperitoneal glucose tolerance test, compared with HFD rats. It also normalized NO‐dependent vasorelaxation increasing endothelial NO synthase (eNOS) phosphorylation in mesenteric arteries of HFD rats. In PVAT from aged (W12m) and HFD rats there was increased expression of chemokines and pro‐inflammatory adipokines, the latter being important contributors to endothelial dysfunction. Infusion of adiponectin reduced these changes.

Conclusions and Implications

Adiponectin normalized endothelial cell function by a mechanism that involved increased eNOS phoshorylation and decreased PVAT inflammation. Detailed characterization of the adiponectin signalling pathway in the vasculature and perivascular fat is likely to provide novel approaches to the management of atherosclerosis and metabolic disease.

Linked Articles

This article is part of a themed section on Molecular Mechanisms Regulating Perivascular Adipose Tissue – Potential Pharmacological Targets? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc
The Interplay Among Children's Negative Family Representations, Visual Processing of Negative Emotions, and Externalizing Symptoms
Authors: Davies Patrick T. , Coe Jesse L. , Hentges Rochelle F. , Sturge‐Apple Melissa L. , van der Kloet Erika
Published: February 2017

This study examined the transactional interplay among children's negative family representations, visual processing of negative emotions, and externalizing symptoms in a sample of 243 preschool children (Mage = 4.60 years). Children participated in three annual measurement occasions. Cross‐lagged autoregressive models were conducted with multimethod, multi‐informant data to identify mediational pathways. Consistent with schema‐based top‐down models, negative family representations were associated with attention to negative faces in an eye‐tracking task and their externalizing symptoms. Children's negative representations of family relationships specifically predicted decreases in their attention to negative emotions, which, in turn, was associated with subsequent increases in their externalizing symptoms. Follow‐up analyses indicated that the mediational role of diminished attention to negative emotions was particularly pronounced for angry faces.