bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple skeletal measurement effectively predicts climbing behaviour in a diverse clade of small mammals
Authors: Nations Jonathan A , Heaney Lawrence R , Demos Terrence C , Achmadi Anang S , Rowe Kevin C , Esselstyn Jacob A
Published: May 2019

Arboreal locomotion allows access to above-ground resources and might have fostered the diversification of mammals. Nevertheless, simple morphological measurements that consistently correlate with arboreality remain indefinable. As such, the climbing habits of many species of mammals, living and extinct, remain speculative. We collected quantitative data on the climbing tendencies of 20 species of murine rodents, an ecologically and morphologically diverse clade. We leveraged Bayesian phylogenetic mixed models (BPMMs), incorporating intraspecific variation and phylogenetic uncertainty, to determine which, if any, traits (17 skeletal indices) predict climbing frequency. We used ordinal BPMMs to test the ability of the indices to place 48 murine species that lack quantitative climbing data into three qualitative locomotor categories (terrestrial, general and arboreal). Only two indices (both measures of relative digit length) accurately predict locomotor styles, with manus digit length showing the best fit. Manus digit length has low phylogenetic signal, is largely explained by locomotor ecology and might effectively predict locomotion across a multitude of small mammals, including extinct species. Surprisingly, relative tail length, a common proxy for locomotion, was a poor predictor of climbing. In general, detailed, quantitative natural history data, such as those presented here, are needed to enhance our understanding of the evolutionary and ecological success of clades.
Novel HILIC-ESI-MS method for urinary profiling of MSUD and methylmalonic aciduria biomarkers
Authors: Mathew Elizabeth Mary , Lewis Leslie , Rao Pragna , Nalini K , Kamath Asha , Moorkoth Sudheer
Published: May 2019

Methyl malonic acid and branched-chain keto acids are important biomarkers for the diagnosis of cobalamin deficiencies and maple syrup urine disease. We report the development and validation of a HILIC-ESI-MS2 method for the quantification of these organic acids from neonatal urine. The samples were 100 times diluted and analyzed on a ZIC-HILIC column with 25-mM formic acid in water: 25-mM formic acid in acetonitrile (45:55) at a flow rate of 0.8 mL/min with a runtime of only 6 minutes. The method demonstrated a lower limit of detection of 10 ng/mL, Limit of Quantification (LOQ) of 50 ng/mL, linearity of r2 ≥ 0.990 and recoveries of 87–105% for all analytes. The intraday and interday precision CV’s were <10% and 12%, respectively. Extensive stability studies demonstrated the analytes to be stable in stock and in matrix with a percent change within ±15%. The Bland–Altman analysis of the developed method with the gold standard GCMS method demonstrated a bias of 0.44, 0.11, 0.009 and –0.19 for methyl malonic acid, 3-methyl-2-oxovaleric acid, 2-hydroxy-3methylbutyric acid and 4-methyl-2-oxovaleric acid, respectively, proving the methods are comparable. The newly developed method involves no derivatization and has a simple sample preparation and a low runtime, enabling it to be easily automated with a high sample throughput in a cost-effective manner.
Developing a High-Performance Liquid Chromatography (HPLC) Method for Simultaneous Determination of Oxytetracycline, Tinidazole and Esomeprazole in Human Plasma
Authors: Sebaiy Mahmoud M , Hassan Wafaa S , Elhennawy Mostafa E
Published: May 2019

A high performance liquid chromatography method had been developed and validated for rapid simultaneous separation and determination of three anti-helicobacter drugs, oxytetracycline (OXY), tinidazole (TIN) and esomeprazole (ESM) in human plasma within 6 minutes. Drugs extraction method from plasma was based on protein precipitation technique. Separation was carried out on a Equisil BDS C18 column (5 μm, 150 × 4.60 mm) using a mobile phase of acetonitrile: 0.025 M KH2PO4 (25: 75, v/v) adjusted to pH 3.50 with ortho-phosphoric acid at ambient temperature. The flow rate was 1 mL/min and maximum absorption was measured using Diode Array (DAD) detector at 285 nm. The retention times of OXY, TIN and ESM were recorded to be 2.68, 3.52 and 5.17 minutes, respectively, indicating a shorter analysis time. Limits of detection were also reported to be 0.10, 0.07 and 0.04 μg/mL for OXY, TIN and ESM, respectively, showing a high degree of the method sensitivity. The method was then validated according to FDA guidelines for the determination of the drugs clinically in human plasma specially regarding pharmacokinetic and bioequivalence studies.
Low hemoglobin at hemodialysis initiation: an international study of anemia management and mortality in the early dialysis period
Authors: Karaboyas Angelo , Morgenstern Hal , Waechter Sandra , Fleischer Nancy L , Vanholder Raymond , Jacobson Stefan H , Sood Manish M , Schaubel Douglas E , Inaba Masaaki , Pisoni Ronald L , Robinson Bruce M
Published: May 2019

Background

Anemia at hemodialysis (HD) initiation is common. Correcting low hemoglobin (Hgb) before HD initiation may improve survival by avoiding potential harms of chronic anemia, high doses of erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in the early HD period, and/or rapid Hgb rise.

Methods

We included 4604 incident HD patients from 21 countries in the Dialysis Outcomes and Practice Patterns Study Phases 4–5 (2009–15). Because low Hgb at HD start may reflect comorbidity or ESA hyporesponse, we restricted our analysis to the 80% of patients who achieved Hgb ≥10 g/dL 91–120 days after HD start (Month 4).

Results

About 53% of these patients had Hgb <10 g/dL in Month 1 (<30 days after HD start); they were younger with a similar comorbidity profile (versus Hgb ≥10 g/dL). Month 1 Hgb was associated with first-year HD mortality (adjusted hazard ratio for 1 g/dL higher Hgb was 0.89; 95% confidence interval: 0.81–0.97), despite minimal differences in Month 4 Hgb. Patients with lower Hgb in Month 1 received higher doses of ESA, but not IV iron, over the first 3 months of HD. Results were consistent when excluding catheter users or adjusting for IV iron and ESA dose over the first 3 months.

Conclusions

Even among patients with Hgb ≥10 g/dL 3 months later, anemia at HD initiation was common and associated with elevated mortality. A more proactive approach to anemia management in advanced chronic kidney disease (CKD) may thus improve survival on HD, though long-term prospective studies of non-dialysis CKD patients are needed.
A loosening prosthesis in a dialysis patient
Authors: Cailleaux Pierre-Emmanuel , Benarbia Seddik , Allard Guillaume , Ureña-Torres Pablo , Cohen-Solal Martine
Published: May 2019

A haemodialysis patient with periprosthetic fractures and a history of corticosteroid use was referred for assessment for bone mineral disorders. Mixed renal osteodystrophy was diagnosed following a bone biopsy. Correction for vitamin D insufficiency did not improve the clinical signs, which prompted a potential diagnosis of hypophosphataemic osteomalacia to be considered. No causes for hypophosphataemia were found, except for phosphate dietary restrictions. Phosphorus supplementation was administered, resulting in an upturn in bone biochemical and histological parameters and increased bone mineral density, thus confirming the diagnosis of hypophosphataemic osteomalacia due to low phosphate intake. Characteristic features related to this diagnosis are shown from three repeated bone biopsies performed during the course of patient follow-up.
Male courtship signal modality and female mate preference in the wolf spider Schizocosa ocreata: results of digital multimodal playback studies
Authors: Kozak Elizabeth C , Uetz George W
Published: May 2019

Females must be able to perceive and assess male signals, especially when they occur simultaneously with those of other males. Previous studies show female Schizocosa ocreata wolf spiders display receptivity to isolated visual or vibratory courtship signals, but increased receptivity to multimodal courtship. It is unknown whether this is true when females are presented with a choice between simultaneous multimodal and isolated unimodal male courtship. We used digital playback to present females with a choice simulating simultaneous male courtship in different sensory modes without variation in information content: 1) isolated unimodal visual versus vibratory signals; 2) multimodal versus vibratory signals; and 3) multimodal versus visual signals. When choosing between isolated unimodal signals (visual or vibratory), there were no significant differences in orientation latency and number of orientations, approaches or receptive displays directed to either signal. When given a choice between multimodal versus vibratory-only male courtship signals, females were more likely to orient to the multimodal stimulus, and directed significantly more orients, approaches and receptivity behaviors to the multimodal signal. When presented with a choice between multimodal and visual-only signals, there were significantly more orients and approaches to the multimodal signal, but no significant difference in female receptivity. Results suggest that signal modes are redundant and equivalent in terms of qualitative responses, but when combined, multimodal signals quantitatively enhance detection and/or reception. This study confirms the value of testing preference behavior using a choice paradigm, as female preferences may depend on the context (e.g., environmental context and social context) in which they are presented with male signals.
High human disturbance decreases individual variability in skink escape behavior
Authors: Williams Dana M , Nguyen Phat-Tan , Chan Kemal , Krohn Madeleine , Blumstein Daniel T
Published: May 2019

Animals living around people may modify their antipredator behavior as a function of proximity to humans, and this response has profound implications for whether or not a population can coexist with humans. We asked whether inland blue-tailed skinks Emoia impar modified their individual antipredator behavior as a function of differential exposure to humans. We conducted multiple consecutive flushes and recorded 2 measures of antipredator response: flight initiation distance (FID), the distance from a threatening stimulus at which an individual flees, and distance fled, the distance an individual fled after a flush. We used a multiple model comparison approach to quantify variation in individual escape behavior across multiple approaches and to test for differences in between-individual variation among populations. We found that individuals tolerated closer approach and fled shorter distances at locations with relatively less human disturbance than at locations with medium and high human disturbance, respectively. In addition, skinks living at high human disturbance sites had less variable FIDs than at low human disturbance sites. Two theories may explain these results. Selection against less favorable phenotypes has reduced behavioral variation in urban habitats and behavioral plasticity allows individuals to flexibly adjust their behavioral patterns in response to human disturbance. These results highlight the importance of studying variation within populations, at the individual level, which may better elucidate the impact that human disturbance has on the behavioral composition of populations.
Anatomy of mitral annulus insights from non-invasive imaging techniques
Authors: Faletra Francesco F , Leo Laura Anna , Paiocchi Vera Lucia , Caretta Alessandro , Viani Giacomo Maria , Schlossbauer Susanne Anna , Demertzis Stefanos , Ho Siew Yen
Published: May 2019

The mitral annulus (MA) is not a continuous ring of connective tissue from which are suspended mitral leaflets. Instead, it is a much more complex structure made up of a mix of fibrous, muscular, and adipose tissues. MA is a key structure in any type of mitral valve repair and recently it has been targeted for transcutaneous devices. Thus, a deep understanding of MA anatomy has never been more important. Traditionally, cardiac anatomy has been described using anatomic specimens. Currently, sophisticated non-invasive techniques allow imaging of MA with a richness of anatomical details unimaginable only two decades ago. The aim of this review is to provide a better understanding of the peculiar aspects of MA as they are revealed through these imaging techniques and discuss clinical implications related to this complex structure.
The Rosa Lee phenomenon and its consequences for fisheries advice on changes in fishing mortality or gear selectivity
Authors: Kraak Sarah B M , Haase Stefanie , Minto Cóilín , Santos Juan
Published: May 2019

When size-selective fishing removes faster-growing individuals at higher rates than slower-growing fish, the surviving populations will become dominated by slower-growing individuals. When this “Rosa Lee phenomenon” is ignored, bias may occur in catch and stock projections. In a length-and-age-based model we quantified the effects through simulations of a simplified fishery on a stock that resembles Western Baltic cod. We compared outcomes of runs with and without taking account of the Rosa Lee phenomenon in scenarios of changes in fishing mortality. We found that, when only fishing rate was changed, the biases in predictions of spawning-stock biomass (SSB), yield and catches of undersized fish were relatively small (<10% in absolute values). When the selectivity parameters of the gear were increased, the bias in the prediction of the catches of undersized fish was very substantial (+120 to 160%). When the selectivity parameters were decreased, the biases in the predictions of SSB, yield and catches of undersized fish, were substantial (25–50% in absolute values). With slower mean growth the biases became more pronounced. We conclude that in short-term forecasts, medium-term projections, and MSE simulations featuring selectivity changes, the Rosa Lee phenomenon should be accounted for, ideally by using length-based models.
Concealing Disease: Trade and Travel Barriers and the Timeliness of Outbreak Reporting
Authors: Worsnop Catherine Z
Published: May 2019

Slow outbreak reporting by states is a key challenge to effectively responding to global health emergencies like Zika, Ebola, and H1N1. Current policy focuses on improving domestic outbreak surveillance capacity globally in order to reduce reporting lags. However, governments also face economic and political incentives to conceal outbreaks, and these incentives largely are ignored in policy discussions. In spite of the policy implications for outbreak response, the “capacity” and “will” explanations have not been systematically examined. Analysis of a dataset coding the timeliness of outbreak reporting from 1996–2014 finds evidence that states’ unwillingness to report—rather than just their inability—leads to delayed reporting. The findings suggest that though building surveillance capacity is critical, doing so may not be sufficient to reduce reporting lags. Policy aimed at encouraging rapid reporting must also mitigate the associated economic and political costs.
Effect of gestation dietary methionine/lysine ratio on placental angiogenesis and reproductive performance of sows1
Authors: Xia Mao , Pan Ye , Guo Liangliang , Wei Xiaowei X , Xiong Jia , Wang Liu , Peng Jie , Wang Chao , Peng Jian , Wei H K
Published: May 2019

The current study aims to evaluate the effects of different gestation dietary Met/Lys (methionine, Met/lysine) ratios on the production performance of sows. Specifically, it measured the effect of Met on plasma urea and AA concentrations and placental vascular density of pregnant sows. A total of 325 multiparous sows (third parity, Large × White) were randomly allocated to five dietary treatments (n = 65) with five dietary Met/Lys ratios 0.27 (nutrient requirements of swine [NRC] 2012 level), 0.32, 0.37, 0.42, and 0.47). The litter size and weight at birth were measured and recorded. Blood samples were obtained on days 0, 40, 90, and 114 of gestation, and placenta samples were collected at parturition. The effects of different dietary Met/Lys ratios on the reproductive performance were evaluated based on the prolificacy of sows as either high (≥13 total piglets born) or low (<13 total piglets born). The results showed that dietary Met/Lys ratio had no significant effect on the reproductive performance of lower prolificacy sows (P > 0.05). However, for high-prolificacy sows, litter weight of born alive significantly increased in 0.37 Met/Lys ratios group compared with control group (P < 0.05). The gestation dietary Met/Lys ratio showed significant quadratic effects on the litter birth weight and percentage of piglets born with weight <0.9 kg (P < 0.05), and the Met/Lys ratios to achieve the best reproductive performance determined to be 0.37. Furthermore, plasma urea concentrations of sows also changed with Met/Lys ratios quadratically (P < 0.05). Increasing dietary Met/Lys ratios elevated the concentration of most plasma AA. Although the dietary Met/Lys ratio had no significant effect on the placental vascular density (P > 0.05), the gestation dietary Met/Lys ratio showed significant quadratic effects on the placental vascular density (P < 0.05). In addition, the birth weight of piglets of high-prolificacy sows was positively correlated with the placental vascular density (P < 0.01). Taken as a whole, the dietary Met/Lys ratio showed a quadratic curve relation with birth weight performance and placental angiogenesis performance, to which 0.37 ratio contributed to the best performance of high-prolificacy sows.
Holographic subregion complexity of a (1+1)-dimensional $p$-wave superconductor
Authors: Fujita Mitsutoshi
Published: May 2019

We analyze the holographic subregion complexity in a three-dimensional black hole with vector hair. This three-dimensional black hole is dual to a (1+1)-dimensional $p$-wave superconductor. We probe the black hole by changing the size of the interval and by fixing $q$ or $T$. We show that the universal part is finite across the superconductor phase transition and has competitive behaviors different from the finite part of the entanglement entropy. The behavior of the subregion complexity depends on the gravitational coupling constant divided by the gauge coupling constant. When this ratio is less than the critical value, the subregion complexity increases as temperature becomes low. This behavior is similar to that of the holographic (1+1)-dimensional $s$-wave superconductor [M. K. Zangeneh, Y. C. Ong, and B. Wang, Phys. Lett. B 771, 130 (2014)]. When the ratio is larger than the critical value, the subregion complexity has a non-monotonic behavior as a function of $q$ or $T$. We also find a discontinuous jump of the subregion complexity as a function of the size of the interval. The subregion complexity has a maximum when it wraps almost the entire spatial circle. Due to competitive behaviors between the normal and condensed phases, the universal term in the condensed phase becomes even smaller than that of the normal phase by probing the black hole horizon at a large interval. This implies that the condensate formed decreases the subregion complexity as in the case of the entanglement entropy.
Wassermann Before Wedding Bells: Premarital Examination Laws in the United States, 1937–1950
Authors: Doroshow Deborah B
Published: May 2019

In the late 1930s, states began to pass laws requiring men and women applying for marriage licences to demonstrate proof of a blood test showing that they did not harbour communicable syphilis. Advocates of the laws positioned marriage as a public health checkpoint to identify new cases of syphilis as part of a broader effort to approach the disease as a public health problem, rather than a moral one. Although the laws appeared to have broad popular support, in reality they were a failed public health intervention. Couples rushed to the altar before laws went into effect and border-hopped to marry in states without blood test laws. The blood tests used to detect syphilis were difficult to interpret and physicians could not agree on a standard definition of communicable disease. But for over 30 years, premarital examination laws represented a tangible government presence in the private lives of most Americans.
Adverse childhood experiences affect sleep duration for up to 50 years later
Authors: Sullivan Kelly , Rochani Haresh , Huang Li-Ting , Donley Diane K , Zhang Jian
Published: May 2019

Study Objectives

The main objective for this study was to assess the association of adverse childhood experiences (ACEs) and subsequent short sleep duration among adults.

Methods

This cross-sectional examination used data from the 2011 Behavioral Risk Factor Surveillance System, a nationwide telephone-administered survey. Participants completed a standardized questionnaire to report childhood experiences of abuse, neglect, household challenges, and sleep time. Multinominal logistic regression analyses included survey weighting procedures and adjusted for age, race, education, income, sex, and body mass index; associations were also examined by age strata, using age as a proxy for time since ACEs occurred.

Results

Complete data were available for 22 403 adults (mean age = 46.66 years) including 14 587 (65%) with optimum sleep duration (7–9 h/night) and 2069 (9%) with short sleep duration (<6 h/night). Compared with adults with optimum sleep duration, the number of ACEs was associated with the odds of short sleep duration (odds ratio [OR] = 1.22, 95% CI = 1.16 to 1.28), and the odds increased as the number of ACEs increased. The association held for each decade of age until the 60s, although the magnitude attenuated. Mental health challenges or poor physical health did not account for the association.

Conclusion

ACEs increased the odds of chronic short sleep duration during adulthood and showed both a time-dependent and dose–response nature. These associations were independent of self-reported mental health challenges or poor physical health. The association of ACEs with short sleep duration throughout the adult lifespan emphasizes the importance of child health and identifying underlying psychological challenges in adults with sleep difficulties.
Olfactory ensheathing cells from the nasal mucosa and olfactory bulb have distinct membrane properties
Authors: Smith Katie E. , Whitcroft Katherine , Law Stuart , Andrews Peter , Choi David , Jagger Daniel J.
Published: May 2019

Transplantation of Olfactory Ensheathing Cells (OECs) is a potential therapy for the regeneration of damaged neurons. While they maintain tissue homeostasis in the olfactory mucosa (OM) and olfactory bulb (OB), their regenerative properties also support the normal sense of smell by enabling continual turnover and axonal regrowth of olfactory sensory neurons (OSNs). However, the molecular physiology of OECs is not fully understood, especially that of OECs from the mucosa. Here, we carried out whole-cell patch clamp recordings from individual OECs cultured from the OM and OB of the adult rat, and from the human OM. A subset of OECs from the rat OM cultured 1-3 days in vitro (DIV) had large weakly rectifying K+ currents, which were sensitive to Ba2+ and desipramine, blockers of Kir4-family channels. Kir4.1 immunofluorescence was detectable in OM cells co-labelled for the OEC marker S100, and found adjacent to axons of OSNs. OECs cultured from rat OB had distinct properties though, displaying strongly rectifying inward currents at hyperpolarized membrane potentials and strongly rectifying outward currents at depolarized potentials. Kir4.1 immunofluorescence was not evident in OECs adjacent to axons of OSNs in the OB. A subset of human OECs cultured from the OM of adults had membrane properties comparable to those of the rat OM, i.e. dominated by Ba2+-sensitive weak inwardly rectifying currents. The membrane properties of peripheral OECs are different to those in central OECs, suggesting they may play distinct roles during olfaction.

Table of Contents Image

Main points

Peripheral and central OECs are functionally distinct

Peripheral OECs have large weak inward rectifier currents

Central OECs have strong inward and outward rectifier currents
Guided proposals for efficient weighted stochastic simulation
Authors: Gillespie Colin S. , Golightly Andrew
Published: May 2019

Rare event probabilities play an important role in the understanding of the behaviour of biochemical systems. Due to the intractability of the most natural Markov jump process representation of a system of interest, rare event probabilities are typically estimated using importance sampling. While the resulting algorithm is reasonably well developed, the problem of choosing a suitable importance density is far from straightforward. We therefore leverage recent developments on simulation of conditioned jump processes to propose an importance density that is simple to implement and requires no tuning. Our results demonstrate superior performance over some existing approaches.
Site-specific effects of online rTMS during a working memory task in healthy older adults
Authors: Beynel Lysianne , Davis Simon W. , Crowell Courtney A. , Dannhauer Moritz , Lim Wesley , Palmer Hannah , Hilbig Susan A. , Brito Alexandra , Hile Connor , Luber Bruce , Lisanby Sarah H. , Peterchev Angel V. , Cabeza Roberto , Appelbaum Lawrence G.
Published: May 2019

The process of manipulating information within working memory (WM) is central to many cognitive functions, but also declines rapidly in old age. Given the importance of WM manipulation for maintaining healthy cognition, improving this process could markedly enhance health-span in older adults. The current pre-registered study tested the potential of online repetitive transcranial magnetic stimulation (rTMS) to enhance WM manipulation in healthy elderly adults. Online 5Hz rTMS was applied over the left lateral parietal cortex of 15 subjects to test the hypothesis that active rTMS would significantly improve performance compared to sham stimulation, and that these effects would be most pronounced in conditions with the highest cognitive demand. rTMS was applied while participants performed a delayed-response alphabetization task with two individually-titrated levels of difficulty. Sham stimulation was applied using an electrical sham coil that produced similar clicking sounds and somatosensory sensation as active stimulation but induced negligible effects on the brain. A stimulation site in left lateral parietal cortex was identified from fMRI activation maps and was targeted using individualized electric field modeling, stereotactic neuronavigation, and real-time robotic positioning, allowing optimal coil placement during the stimulation. Contrary to the a priori hypothesis, active rTMS significantly decreased accuracy relative to sham, and only in the hardest difficulty level. These results, therefore, demonstrate engagement of cortical WM processing, but not the anticipated facilitation, and provide a prescription for future studies that may attempt to enhance memory through application of different stimulation parameters.

Highlights

This study is one of the first attempts to enhance WM manipulation with online rTMS

Online 5Hz rTMS and sham were applied over the left parietal cortex of older adults

Individualized fMRI and electric field modeling were used to optimize targeting

Contrary to expectations, rTMS disrupted working memory manipulation abilities

This demonstrates that parietal cortex is involved in WM and modifiable with rTMS
Microbial Food Safety in the Maryland Direct-to-Consumer Poultry Supply Chain
Authors: Baron Patrick A. , Love David C. , Ludwig Shanna , Dalton Kathryn , Larsen Jesper , Innes Gabriel K. , Davis Meghan F. , Heaney Christopher D.
Published: May 2019

Direct-to-consumer food marketing is a growing niche in the United States food supply chain. Food animal producers who use direct marketing may employ different production models and standard practices from producers selling animal products to the conventional food system. Direct-to-consumer food supply chains (generally and specifically regarding food animal products) are relatively unexplored in food safety and health research. We conducted a cross-sectional, market-basket analysis of the Maryland direct-to-consumer poultry supply chain to assess food safety. We analyzed 40 direct-to-consumer commercial poultry meat products (one product per farm) forEscherichia coli, Staphylococcus aureusandSalmonella spp.using culture-based methods. Isolates underwent antimicrobial susceptibility testing.E. coliandS. aureuswere recovered from 9/40 (23%) and 12/40 (30%) of poultry meat samples, respectively. Of interest for comparing direct-market and mainstream supply chains for food safety risks, noSalmonellaisolates were recovered from any direct-market sampled poultry products and no multidrug resistance was observed inE. coliandS. aureusisolates. Microbial outcomes were compared to a survey of poultry production and processing practices within the same study population.

Importance

This study demonstrates substantially lower rates of antimicrobial-resistant (AMR) microbial pathogens in the market-basket products from Maryland direct-market broiler poultry supply chain compared to rates of AMR in the conventional supply chain for similar retail meat products from NARMS. We further describe the landscape of the statewide supply chain for direct-market poultry, focusing on characteristics related to risk management strategies applied to microbial food safety. These findings are of public health significance for both the research and policy communities; these data provide an initial evidence base for more targeted research evaluating potential risk factors for microbial food safety in the direct-to-consumer supply chain. These data will also assist the Maryland Department of Agriculture and other state-level agencies with oversight of food safety issues to guide policy efforts for direct-market poultry production and sales.
Benchmarking workflows to assess performance and suitability of germline variant calling pipelines in clinical diagnostic assays
Authors: Krishnan Vandhana , Utiramerur Sowmi , Ng Zena , Datta Somalee , Snyder Michael P. , Ashley Euan A.
Published: May 2019

Benchmarking the performance of complex analytical pipelines is an essential part of developing Laboratory Developed Assays (LDT). Reference samples and benchmark calls published by Genome in a Bottle (GIAB) Consortium have enabled the evaluation of analytical methods. However, the performance of such methods is not uniform across the different regions of the genome/exome and different variant types and lengths. Here we present a scalable and reproducible, cloud-based benchmarking workflow that can be used by clinical laboratories to rapidly access and validate the performance of LDT assays, across their regions of interest and reportable range, using a broad set of benchmarking samples.
Genome-wide RNAi screen for context-dependent tumor suppressors identified using in vivo models for neoplasia in Drosophila
Authors: Groth Casper , Vaid Pooja , Khatpe Aditi , Prashali Nelchi , Ahiya Avantika , Andrejeva Diana , Chakladar Madhumita , Nagarkar Sanket , Paul Rachel , Eichenlaub Teresa , Herranz Hector , Sridhar TS , Cohen Stephen M. , Shashidhara LS
Published: May 2019

Genetic approaches in Drosophila have successfully identified many genes involved in regulation of growth control as well as genetic interactions relevant to the initiation and progression of cancer in vivo. Here, we report on large-scale RNAi-based screens to identify potential tumor suppressor genes that interact with known cancer-drivers: The Epidermal Growth Factor Receptor and the Hippo pathway transcriptional cofactor Yorkie. These screens were designed to identify genes whose depletion drove tissue expressing EGFR or Yki from a state of benign overgrowth into neoplastic transformation in vivo. We also report on an independent screen aimed to identify genes whose depletion suppressed formation of neoplastic tumors in an existing EGFR-dependent neoplasia model. Many of the positives identified here are known to be functional in growth control pathways. We also find a number of novel connections to Yki and EGFR driven tissue growth, mostly unique to one of the two. Thus, resources provided here would be useful to all researchers who study negative regulators of growth in the context of activated EGFR and/or Yki and positive regulators of growth in the context of activated EGFR.
Selection following gene duplication shapes recent genome evolution in the pea aphid Acyrthosiphon pisum
Authors: Fernández Rosa , Marcet-Houben Marina , Legeai Fabrice , Richard Gautier , Robin Stéphanie , Wucher Valentin , Pegueroles Cinta , Gabaldón Toni , Tagu Denis
Published: May 2019

Ecology of insects is as wide as their diversity, which reflects their high capacity of adaptation in most of the environments of our planet. Aphids, with over 4,000 species, have developed a series of adaptations including a high phenotypic plasticity and the ability to feed on the phloem-sap of plants, which is enriched in sugars derived from photosynthesis. Recent analyses of aphid genomes have indicated a high level of shared ancestral gene duplications that might represent a basis for genetic innovation and broad adaptations. In addition, there is a large number of recent, species-specific gene duplications whose role in adaptation remains poorly understood. Here, we tested whether duplicates specific to the pea aphid Acyrthosiphon pisum are related to genomic innovation by combining comparative genomics, transcriptomics, and chromatin accessibility analyses. Consistent with large levels of neofunctionalization, we found that most of the recent pairs of gene duplicates evolved asymmetrically, showing divergent patterns of positive selection and gene expression. Genes under selection involved a plethora of biological functions, suggesting that neofunctionalization and tissue specificity, among other evolutionary mechanisms, have orchestrated the evolution of recent paralogs in the pea aphid and may have facilitated host-symbiont cooperation. Our comprehensive phylogenomics analysis allowed to tackle the history of duplicated genes to pave the road towards understanding the role of gene duplication in ecological adaptation.
Is adaptation limited by mutation? A timescale-dependent effect of genetic diversity on the adaptive substitution rate in animals
Authors: Rousselle M , Simion P , Tilak MK , Figuet E , Nabholz B , Galtier N
Published: May 2019

Whether adaptation is limited by the beneficial mutation supply is a long-standing question of evolutionary genetics, which is more generally related to the determination of the adaptive substitution rate and its relationship with the effective population size Ne. Empirical evidence reported so far is equivocal, with some but not all studies supporting a higher adaptive substitution rate in large-Nethan in small-Nespecies.

We gathered coding sequence polymorphism data and estimated the adaptive amino-acid substitution rate ωa, in 50 species from ten distant groups of animals with markedly different population mutation rate θ. We reveal the existence of a complex, timescale dependent relationship between species adaptive substitution rate and genetic diversity. We find a positive relationship between ωaand θ among closely related species, indicating that adaptation is indeed limited by the mutation supply, but this was only true in relatively low-θ taxa. In contrast, we uncover a weak negative correlation between ωaand θ at a larger taxonomic scale. This result is consistent with Fisher’s geometrical model predictions and suggests that the proportion of beneficial mutations scales negatively with species’ long-term Ne.
Extracting T Cell Function and Differentiation Characteristics from the Biomedical Literature
Authors: Czech Eric , Hammerbacher Jeff
Published: May 2019

The role of many cytokines and transcription factors in the function and development of human T cells has been the subject of extensive research, however much of this work only demonstrates experimental findings for a relatively small portion of the molecular signaling network that enables the plasticity inherent to these cells. We apply recent advancements in methods for weak supervision and transfer learning for natural language models to aid in extracting these individual findings as 283k cell type, cytokine, and transcription factor relations from 64k relevant documents (53k full-text PMC articles and 11k PubMed abstracts). All data, results and source code available athttps://github.com/hammerlab/t-cell-relation-extraction.
A short review of machine learning methods for classifying the outcome of Gestational Diabetes
Authors: Banerji Shreeya
Published: May 2019

Diabetes mellitus is a growing problem, especially in developing countries. People suffering from diabetes have an increased risk of developing a number of serious health problems. Consistently high blood glucose levels can lead to serious diseases affecting the heart and blood vessels, eyes, kidney, etc. In addition, people with diabetes also have a higher risk of developing infections.

This paper aims to use suitable data mining and classification techniques which include the Logit model, the Probit model, the Classification tree technique, Artificial Neural Networks, Support Vector Machines, Ridge Regression technique and the Least Absolute Shrinkage and Selection Operator(LASSO) in order to determine the best method which can be used to classify the patients as suffering from gestational diabetes or not. The misclassification rate is calculated for different methods and the method having the least misclassification rate is said to be the most suitable to be applied to the given data, which is the PIMA Indians diabetes dataset.
The TFIIH subunits p44/p62 act as a damage sensor during nucleotide excision repair
Authors: Barnett JT , Kuper J , Koelmel W , Kisker C , Kad NM
Published: May 2019

Nucleotide excision repair (NER) protects the genome following exposure to diverse types of DNA damage, including UV light and chemotherapeutics. Mutations in mammalian NER genes lead to diseases such as xeroderma pigmentosum, trichothiodystrophy, and Cockayne syndrome. In eukaryotes, the major transcription factor TFIIH is the central hub of NER. The core components of TFIIH include the helicases XPB, XPD, and five ‘structural’ subunits. Two of these structural TFIIH proteins, p44 and p62 remain relatively unstudied; p44 is known to regulate the helicase activity of XPD during NER whereas p62’s role is thought to be structural. However, a recent cryo-EM structure shows that p44, p62, and XPD make extensive contacts within TFIIH, with part of p62 occupying XPD’s DNA binding site. This observation implies a more extensive role in DNA repair beyond the structural integrity of TFIIH. Here, we show that p44 stimulates XPD’s ATPase but upon encountering DNA damage, further stimulation is only observed when p62 is part of the ternary complex; suggesting a role for the p44/p62 heterodimer in TFIIH’s mechanism of damage detection. Using single molecule imaging, we demonstrate that p44/p62 independently interacts with DNA; it is seen to diffuse, however, in the presence of UV-induced DNA lesions the complex stalls. Combined with the analysis of a recent cryo-EM structure we suggest that p44/p62 acts as a novel DNA-binding entity within TFIIH that is capable of recognizing DNA damage. This revises our understanding of TFIIH and prompts more extensive investigation into the core subunits for an active role during both DNA repair and transcription.
gwasrapidd: an R package to query, download and wrangle GWAS Catalog data
Authors: Magno Ramiro , Maia Ana -Teresa
Published: May 2019

Motivation

The NHGRI Catalog of Published Genome-Wide Association Studies (GWAS) Catalog has collected, curated, and made available data from over 3 900 studies. The recently developed GWAS Catalog REST API is the only method allowing programmatic access to this resource.

Results

Here, we describe gwasrapidd, an R package that provides a client interface to the GWAS Catalog REST API, representing an important software counterpart to the server-side component. gwasrapidd enables users to quickly retrieve, filter and integrate data with comprehensive bioinformatics analysis tools, which is particularly critical for those looking into functional characterisation of risk loci.

Availability

gwasrapidd is freely available under an MIT License, and can be accessed from https://github.com/ramiromagno/gwasrapidd.
The evolutionary origins and diversity of the neuromuscular system of paired appendages in batoids
Authors: Turner Natalie , Mikalauskaite Deimante , Barone Krista , Flaherty Kathleen , Senevirathne Gayani , Adachi Noritaka , Shubin Neil H , Nakamura Tetsuya
Published: May 2019

Appendage patterning and evolution have been active areas of inquiry for the past two centuries. While most work has centered on the skeleton, particularly that of amniotes, the evolutionary origins and molecular underpinnings of the neuromuscular diversity of fish appendages have remained enigmatic. The fundamental pattern of segmentation in amniotes, for example, is that all muscle precursors and spinal nerves enter either the paired appendages or body wall at the same spinal level. The condition in finned vertebrates is not understood. To address this gap in knowledge, we investigated the development of muscles and nerves in unpaired and paired fins of skates and compared them to those of chain catsharks. During skate and shark embryogenesis, cell populations of muscle precursors and associated spinal nerves at the same axial level contribute to both appendages and body wall, perhaps representing an ancestral condition of gnathostome appendicular neuromuscular systems. Remarkably in skates, this neuromuscular bifurcation as well as colinearHoxexpression extend posteriorly to pattern a broad paired fin domain. In addition, we identified migratory muscle precursors (MMPs), which are known to develop into paired appendage muscles withPax3andLbx1gene expression, in the dorsal fins of skates. Our results suggest that muscles of paired fins have evolved via redeployment of the genetic program of MMPs that were already involved in dorsal fin development. Appendicular neuromuscular systems most likely have emerged as side branches of body wall neuromusculature and have been modified to adapt to distinct aquatic and terrestrial habitats.
Histone acetylome-wide association study of tuberculosis
Authors: del Rosario Ricardo C.H. , Poschmann Jeremie , Kumar Pavanish , Cheng Catherine Y. , Ong Seow Theng , Hajan Hajira Shreen , Kumar Dilip , Marzuki Mardiana , Lu Xiaohua , Lee Andrea , Tang Yanxia , Chee Cynthia Bin Eng , Lim Carey , Lee Bernett , Lum Josephine , Zolezzi Francesca , Poidinger Michael , Rotzschke Olaf , Khor Chiea Chuen , Wang Yee T. , Chandy K. George , De Libero Gennaro , Singhal Amit , Prabhakar Shyam
Published: May 2019

Host-cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here, we describe the first histone acetylome-wide association study (HAWAS) of an infectious disease, based on genome-wide H3K27 acetylation profiling of peripheral granulocytes and monocytes from subjects with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Chinese discovery cohort, which were validated in a subsequent multi-ethnic cohort, thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression in a third cohort. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulated Akt-mTOR signaling and promoted Mtb clearance in vitro. We performed histone acetylation QTL analysis on the dataset and identified candidate causal variants for immune phenotypes. Our study serves as proof-of-principle for HAWAS to infer mechanisms of host response to pathogens.
Exploring Contextual Interference in Implicit and Explicit Motor Learning
Authors: Dang Kristy V. , Parvin Darius E. , Ivry Richard B.
Published: May 2019

The classic advice given to anyone learning a new skill is “practice makes perfect.” While this provides a good general rule to follow, it lacks any detail on what form of practice will efficiently maximize learning. So when faced with the task of acquiring multiple skills, what is the optimal way to learn? Would it be more beneficial to master each skill separately or learn them all at once in an interleaved fashion? A concept known as contextual interference suggests that using a random practice schedule leads to better retention than a blocked one. There are some motor learning studies that are consistent with this hypothesis and some that are not. In order to explore these conflicting results, we applied contextual interference to a simple reaching task that could allow us to observe its effects to various components of motor learning. We had participants learn three different visuomotor rotations and manipulated interference by placing them in groups characterized by how training targets are ordered (blocked vs. random). Using reaction time and hand angle as our measures of performance, we found that participants who experienced a random practice schedule had significant improvements in their ability to retain information, which was manifest as higher levels of implicit adaptation and faster reaction times. However, this did not necessarily mean the information was executed accurately since hand angles did not differ between groups. These findings suggest contextual interference will be most advantageous in situations that require fast explicit recall of a motor plan to use rather than those that emphasize accuracy.
Inferring diploid 3D chromatin structures from Hi-C data
Authors: Cauer Alexandra Gesine , Yardimci Gürkan , Vert Jean-Philippe , Varoquaux Nelle , Noble William Stafford
Published: May 2019

The 3D organization of the genome plays a key role in many cellular processes, such as gene regulation, differentiation, and replication. Assays like Hi-C measure DNA-DNA contacts in a high-throughput fashion, and inferring accurate 3D models of chromosomes can yield insights hidden in the raw data. For example, structural inference can account for noise in the data, disambiguate the distinct structures of homologous chromosomes, orient genomic regions relative to nuclear landmarks, and serve as a framework for integrating other data types. Although many methods exist to infer the 3D structure of haploid genomes, inferring a diploid structure from Hi-C data is still an open problem. Indeed, the diploid case is very challenging, because Hi-C data typically does not distinguish between homologous chromosomes. We propose a method to infer 3D diploid genomes from Hi-C data. We demonstrate the accuarcy of the method on simulated data, and we also use the method to infer 3D structures for mouse chromosome X, confirming that the active homolog exhibits a bipartite structure, whereas the active homolog does not.