bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bone Health Intervention for Chinese Immigrants in Santa Clara County
Authors: Zou Joanne , Hampton Michelle DeCoux , Shade Kate , Kaku Leonard
Published: July 2017

BACKGROUND:

Among Chinese immigrants, osteoporosis is undertreated, misdiagnosed, and a leading cause of fragility fractures. In orthopaedic surgery departments, prevention education and health behavior change programs are necessary to improve their bone health.

PURPOSE:

The purpose of this study was to examine the effectiveness of an osteoporosis prevention education program on participants' self-efficacy with regard to exercise and nutrition when provided by an orthopaedic surgery team during an annual Chinese Health Fair in Santa Clara County, CA.

METHODS:

This pilot study used a single-group pretest and posttest design. Chinese immigrants at risk of osteoporosis were recruited during a 1-day health fair. The Bone Health Intervention (BHI) included orthopaedic surgeon consultation, visual aids including osteoporosis images and bone models, a video that included a discussion on calcium and vitamin D in the Chinese diet and culturally-acceptable exercise, and osteoporosis educational handouts. The Osteoporosis Self-Efficacy Scale (OSES) was utilized to measure participants' confidence in the ability to participate in self-care behaviors related to physical activity and calcium intake before and after the intervention. Paired t tests were used to compare participants' OSES scores pre- and postintervention.

RESULTS:

There was a significant increase in mean OSES scores postintervention, indicating that the intervention could be an effective method of increasing participants' self-efficacy regarding calcium intake and time spent in exercising.

CONCLUSION:

These results indicate that a culturally meaningful education program can potentially reduce fragility fracture risk. Orthopaedic health providers are ideal candidates to deliver preventive care education to improve outcomes for Chinese immigrants.
A Standardized Arabic Reading Acuity Chart: The Balsam Alabdulkader-Leat Chart
Authors: Alabdulkader Balsam , Leat Susan J.
Published: July 2017

PURPOSE

The aim of this study was to develop and validate the first standardized Arabic continuous text near-visual-acuity chart, the Balsam Alabdulkader-Leat (BAL) chart.

METHODS

Three versions of the BAL chart were created from previously validated sentences. Reading acuity (RA) and reading speed in standard-length words per minute (SLWPM) were measured for three versions of the BAL chart and three English charts (MNREAD, Colenbrander, and Radner) for 86 bilingual adults with normal vision aged 15 to 59 years. The RA and SLWPM were compared using analysis of variance. To analyze agreement between the charts, Bland-Altman plots were used. Normal visual acuity (0.00 logMAR [log minimum angle of resolution]) was calibrated for the BAL chart with linear regression analysis.

RESULTS

Average RAs for BAL1, BAL2, and BAL3 were 0.62, 0.64 and 0.65 log-point print, respectively, which were statistically significantly different (repeated-measures analysis of variance, P < .05), but not considered clinically significant. The coefficients of agreement for RA between the BAL charts were 0.054 (between 1 and 2), 0.061 (between 2 and 3), and 0.059 (between 1 and 3). Linear regression between the average RA for the BAL chart and the MNREAD and Radner charts showed that 0.7 log-point size at 40 cm is equivalent to 0.00 logMAR, and the new BAL chart was labeled accordingly. Mean SLWPM for the BAL charts was 201, 195, and 195 SLWPM, respectively, and for the Colenbrander, MNREAD, and Radner charts was 146, 171, and 146, respectively. The coefficients of agreement for log-SLWPM between BAL1 and BAL2, BAL2 and BAL3, and BAL1 and BAL3 were 0.063, 0.064, and 0.057 log-SLWPM, respectively.

CONCLUSIONS

The BAL chart showed high interchart agreement. It is recommended for accurate near performance measures in Arabic for both research and clinical settings.
Investing in Physicians Is Investing in Patients: Enhancing Patient Safety Through Physician Health and Well-Being Research
Authors: Brooks Elizabeth , Gundersen Doris C. , Gendel Michael H.
Published: July 2017

Keeping medical practitioners healthy is an important consideration for workforce satisfaction and retention, as well as public safety. However, there is limited evidence demonstrating how to best care for this group. The absence of data is related to the lack of available funding in this area of research. Supporting investigations that examine physician health often “fall through the cracks” of traditional funding opportunities, landing somewhere between patient safety and workforce development priorities. To address this, funders must extend the scope of current grant opportunities by broadening the scope of patient safety and its relationship to physician health. Other considerations are allocating a portion of doctors' licensing fees to support physician health research and encourage researchers to collaborate with interested stakeholders who can underwrite the costs of studies. Ultimately, funding studies of physician health benefits not only the community of doctors but also the millions of patients receiving care each year.
Oncologic Outcome and Morbidity in the Elderly Rectal Cancer Patients After Preoperative Chemoradiotherapy and Total Mesorectal Excision
Authors: Sung Soo-Y , Jang Hong S. , Kim Sung H. , Jeong Jae U. , Jeong Songmi , Song Jin H. , Chung Mi J. , Cho Hyeon M. , Kim Hyung J. , Kim Jun-Gi , Lee In K. , Lee Jong H.
Published: July 2017

Objective:

To determine the toxicity and oncologic outcome of neoadjuvant chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME) in the elderly (≥70 yrs) and younger (<70 yrs) rectal cancer patients.

Background:

Sufficient data for elderly rectal cancer patients who received definitive trimodality have not been accumulated yet.

Patients and Methods:

A total of 1232 rectal cancer patients who received neoadjuvant CRT and TME were enrolled in this study. After propensity-score matching, 310 younger patients and 310 elderly patients were matched with 1:1 manner. Treatment response, toxicity, surgical outcome, recurrence, and survival were assessed and compared between the 2 groups of patients.

Results:

The median age was 58 years for the younger patient group and 74 years for the elderly group. Pathologic complete response rates were not significantly different between the 2 groups (younger and elderly: 17.1% vs 14.8%, P = 0.443). The 5-year recurrence-free survival (younger and elderly: 67.7% vs 65.5%, P = 0.483) and overall survival (younger and elderly: 82.9% vs. 79.5%, P = 0.271) rates were not significantly different between the 2 groups either. Adjuvant chemotherapy after surgery was less frequently delivered to the elderly than that to younger patients (83.9% vs 69.0%). Grade 3 or higher acute hematologic toxicity was observed more frequently in the elderly than that in the younger group (9.0% vs 16.1%, P = 0.008). Late complication rate was higher in the elderly group compared with that in the younger group without statistical significance (2.6% vs 4.5%, P = 0.193).

Conclusions:

Although acute hematologic toxicity was observed more frequently in the elderly patients than that in the younger patients, elderly rectal cancer patients with good performance status who received preoperative CRT and TME showed favorable tumor response and recurrence-free survival similar to younger patients.
Long Exercise Test in the Interattack Period of Periodic Paralysis: A Useful and Sensitive Diagnostic Tool
Authors: Jin Jiaoting , Hu Fangfang , Li Min , Shang Suhang , Qin Xing , Cao Hongmei , Dang Jingxia
Published: July 2017

Purpose:

The reference values of long exercise test are inconsistent in previous studies. Our research aims to determine the reference values and improve diagnostic efficiency of long exercise test in periodic paralysis.

Methods:

In this study, 100 healthy controls, 35 non–periodic paralysis patients, and 47 patients with periodic paralysis were recruited. The procedures of long exercise test were conducted following McMannis(1986) method.

Results:

The decrease rate in compound muscle action potential amplitudes was correlated with gender, and it was not influenced by age, height, weight, and exercise. After analyzing receiver operating characteristic curves, the compound muscle action potential amplitude decrease rate was stratified by sex. The mean area under the curve, sensitivity, and specificity were higher in male and female than all pooled subjects. The reference values of compound muscle action potential amplitude decrease rate were 46.8% in male and 26.9% in female, respectively.

Conclusions:

The long exercise test is a useful and sensitive diagnostic tool for primary periodic paralysis and thyrotoxic periodic paralysis. However, the reference values should be set by sex, which has better diagnostic performance, sensitivity, and specificity.
The York Gospels: a one thousand year biological palimpsest
Authors: Teasdale Matthew D. , Fiddyment Sarah , Vnouček Jiří , Mattiangeli Valeria , Speller Camilla , Binois Annelise , Carver Martin , Dand Catherine , Newfield Timothy P. , Webb Christopher C. , Bradley Daniel G. , Collins Matthew J.
Published: July 2017

Medieval manuscripts, carefully curated and conserved, represent not only an irreplaceable documentary record but also a remarkable reservoir of biological information. Palaeographic and codicological investigation can often locate and date these documents with remarkable precision. The York Gospels (York Minster Ms. Add. 1) is one such codex, one of only a small collection of pre-conquest Gospel books to have survived the Reformation. By extending the non-invasive triboelectric (eraser-based) sampling technique eZooMS, to include the analysis of DNA we report a cost effective and simple-to-use biomolecular sampling technique. We apply this combined methodology to document for the first time a rich palimpsest of biological information contained within the York Gospels, which has accumulated over the 1,000 year lifespan of this cherished object that remains an active participant in the life of York Minster. This biological data provides insights into the decisions made in the selection of materials, the construction of the codex and the use history of the object.
Genome-wide transcription factor binding in leaves from C3and C4grasses
Authors: Burgess Steven J. , Reyna-Llorens Ivan , Stevenson Sean R. , Singh Pallavi , Jaeger Katja , Hibberd Julian M.
Published: July 2017

The majority of plants use C3photosynthesis, but over sixty independent lineages of angiosperms have evolved the C4pathway. In most C4species, photosynthesis gene expression is compartmented between mesophyll and bundle sheath cells. We performed DNaseI-SEQ to identify genome-wide profiles of transcription factor binding in leaves of the C4grassesZea mays,Sorghum bicolorandSetaria italicaas well as C3Brachypodium distachyon. In C4species, while bundle sheath strands and whole leaves shared similarity in the broad regions of DNA accessible to transcription factors, the short sequences bound varied. Transcription factor binding was prevalent in gene bodies as well as promoters, and many of these sites could represent duons that impact gene regulation in addition to amino acid sequence. Although globally there was little correlation between any individual DNaseI footprint and cell-specific gene expression, within individual species transcription factor binding to the same motifs in multiple genes provided evidence for shared mechanisms governing C4photosynthesis gene expression. Furthermore, interspecific comparisons identified a small number of highly conserved transcription factor binding sites associated with leaves from species that diverged around 60 million years ago. These data therefore provide insight into the architecture associated with C4photosynthesis gene expression in particular and characteristics of transcription factor binding in cereal crops in general.

One sentence summary

Genome-wide patterns of transcription factor bindingin vivodefined by DNaseI for leaves of C3and C4grasses
The effects of an 8-week mindful eating intervention on anticipatory reward responses in striatum and midbrain
Authors: Janssen Lieneke K , Duif Iris , Speckens Anne EM , van Loon Ilke , Wegman Joost , de Vries Jeanne HM , Cools Roshan , Aarts Esther
Published: July 2017

Obesity is a highly prevalent disease, usually resulting from chronic overeating. Accumulating evidence suggests that increased neural responses during the anticipation of high-calorie food play an important role in overeating. A promising method for counteracting enhanced food anticipation in overeating might be mindfulness-based interventions (MBIs). However, the neural mechanisms by which MBIs can affect food reward anticipation are unclear. In this randomized, actively controlled study, the primary objective was to investigate the effect of an 8-week mindful eating intervention on reward anticipation. On the neural level, we hypothesized that mindful eating would decrease striatal reward anticipation responses. Additionally, responses in the midbrain – from which the reward pathways originate – were explored. Using functional magnetic resonance imaging (fMRI), we tested 58 healthy participants with a wide body mass index range (BMI: 19-35 kg/m2), motivated to change their eating behavior. During scanning they performed an incentive delay task, measuring neural reward anticipation responses to caloric and monetary cues before and after 8 weeks of mindful eating or educational cooking (active control). Compared with the educational cooking intervention, mindful eating affected neural reward anticipation responses, with relatively reduced caloric versus monetary reward responses. This effect was, however, not seen in the striatum, but only in the midbrain. The secondary objective was to assess temporary and long-lasting (one year follow-up) intervention effects on self-reported eating behavior and anthropometric measures (BMI, waist circumference, waist-to-hip-ratio (WHR)). We did not observe effects of the mindful eating intervention on eating behavior. Instead, the control intervention showed temporary beneficial effects on BMI, waist circumference, and diet quality, but not on WHR or self-reported eating behavior, as well as long-lasting increases in knowledge about healthy eating. These results suggest that an 8-week mindful eating intervention may have decreased the relative salience of food cues by affecting midbrain but not striatal reward responses. However, these exploratory results should be verified in confirmatory research.

The primary and secondary objectives of the study were registered in the Dutch Trial Register (NTR): NL4923 (NTR5025).
Naked mole-rat acid-sensing ion channel 3 forms nonfunctional homomers, but functional heteromers
Authors: Schuhmacher Laura-Nadine , Callejo Gerard , Srivats Shyam , Smith Ewan St. John
Published: July 2017

Acid-sensing ion channels (ASICs) form both homotrimeric and heterotrimeric ion channels that are activated by extracellular protons and are involved in a wide range of physiological and pathophysiological processes, including pain and anxiety. ASIC proteins can form both homotrimeric and heterotrimeric ion channels. The ASIC3 subunit has been shown to be of particular importance in the peripheral nervous system with pharmacological and genetic manipulations demonstrating a role in pain. Naked mole-rats, despite having functional ASICs, are insensitive to acid as a noxious stimulus and show diminished avoidance of acidic fumes, ammonia and carbon dioxide. Here we cloned naked mole-rat ASIC3 (nmrASIC3) and used a cell surface biotinylation assay to demonstrate that it traffics to the plasma membrane, but using whole-cell patch-clamp electrophysiology we observed that nmrASIC3 is insensitive to both protons and the non-proton ASIC3 agonist 2-Guanidine-4-methylquinazoline (GMQ). However, in line with previous reports of ASIC3 mRNA expression in dorsal root ganglia (DRG) neurons, we found that the ASIC3 antagonist APETx2 reversibly inhibits ASIC-like currents in naked mole-rat DRG neurons. We further show that like the proton-insensitive ASIC2b and ASIC4, nmrASIC3 forms functional, proton sensitive heteromers with other ASIC subunits. An amino acid alignment of ASIC3s between 9 relevant rodent species and human identified unique sequence differences that might underlie the proton insensitivity of nmrASIC3. However, introducing nmrASIC3 differences into rat ASIC3 (rASIC3) produced only minor differences in channel function, and replacing nmrASIC3 sequence with that of rASIC3 did not produce a proton-sensitive ion channel. Our observation that nmrASIC3 forms nonfunctional homomers may reflect a further adaptation of the naked mole-rat to living in an environment with high-carbon dioxide levels.
Machine Learning for Large-Scale Quality Control of 3D Shape Models in Neuroimaging
Authors: Petrov Dmitry , Gutman Boris A. , (Julie) Yu Shih-Hua , van Erp Theo G.M. , Turner Jessica A. , Schmaal Lianne , Veltman Dick , Wang Lei , Alpert Kathryn , Isaev Dmitry , Zavaliangos-Petropulu Artemis , Ching Christopher R.K. , Calhoun Vince , Glahn David , Satterthwaite Ted , Andreasen Ole Andreas , Borgwardt Stefan , Howells Fleur , Groenewold Nynke , Voineskos Aristotle , Radua Joaquim , Potkin Steven G. , Crespo-Facorro Benedicto , Tordesillas-Gutiérrez Diana , Shen Li , Lebedeva Irina , Spalletta Gianfranco , Donohoe Gary , Kochunov Peter , Rosa Pedro G.P. , James Anthony , Dannlowski Udo , Baune Bernhard T. , Aleman André , Gotlib Ian H. , Walter Henrik , Walter Martin , Soares Jair C. , Gur Ruben C. , Doan N. Trung , Agartz Ingrid , Westlye Lars T. , Harrisberger Fabienne , Riecher-Rössler Anita , Uhlmann Anne , Stein Dan J. , Dickie Erin W. , Pomarol-Clotet Edith , Fuentes-Claramonte Paola , Canales-Rodríguez Erick Jorge , Salvador Raymond , Huang Alexander J. , Roiz-Santiañez Roberto , Cong Shan , Tomyshev Alexander , Piras Fabrizio , Vecchio Daniela , Banaj Nerisa , Ciullo Valentina , Hong Elliot , Busatto Geraldo , Zanetti Marcus V. , Serpa Mauricio H. , Cervenka Simon , Kelly Sinead , Grotegerd Dominik , Sacchet Matthew D. , Veer Ilya M. , Li Meng , Wu Mon-Ju , Irungu Benson , Thompson Paul M. ,   for the ENIGMA consortium
Published: July 2017

As very large studies of complex neuroimaging phenotypes become more common, human quality assessment of MRI-derived data remains one of the last major bottlenecks. Few attempts have so far been made to address this issue with machine learning. In this work, we optimize predictive models of quality for meshes representing deep brain structure shapes. We use standard vertex-wise and global shape features computed homologously across 19 cohorts and over 7500 human-rated subjects, training kernelized Support Vector Machine and Gradient Boosted Decision Trees classifiers to detect meshes of failing quality. Our models generalize across datasets and diseases, reducing human workload by 30-70%, or equivalently hundreds of human rater hours for datasets of comparable size, with recall rates approaching inter-rater reliability.
Temporal transitions of spontaneous brain activity
Authors: Ma Zhiwei , Zhang Nanyin
Published: July 2017

Spontaneous brain activity, typically investigated using resting-state fMRI (rsfMRI), provides a measure of inter-areal resting-state functional connectivity (RSFC). Previous rsfMRI studies mainly focused on spatial characteristics of RSFC, but the temporal relationship between RSFC patterns is still elusive. Particularly, it remains unknown whether separate RSFC patterns temporally fluctuate in a random manner, or transit in specific orders. Here we investigated temporal transitions between characteristic RSFC patterns in awake rats and humans. We found that transitions between RSFC patterns were reproducible and significantly above chance, suggesting that RSFC pattern transitions were nonrandom. The organization of RSFC pattern transitions in rats was analyzed using graph theory. Pivotal RSFC patterns in transitions were identified including hippocampal, thalamic and striatal networks. This study has revealed nonrandom temporal relationship between characteristic RSFC patterns in both rats and humans. It offers new insights into understanding the spatiotemporal dynamics of spontaneous activity in the mammalian brain.
Linguistically deprived children: meta-analysis of published research underlines the importance of early syntactic language use for normal brain development
Authors: Vyshedskiy Andrey , Shreyas Mahapatra , Dunn Rita
Published: July 2017

We analyzed all published reports of individuals not exposed to syntactic language until puberty: two feral children, who grew up without hearing any language, and eight deaf linguistic isolates, who grew up communicating to their families using homesign or kitchensign, a system of gestures which allows them to communicate simple commands but lacks much in the way of syntax. A common observation in these individuals is the lifelong difficulty understanding syntax and spatial prepositions, even after many years of rehabilitation. This debilitating condition stands in stark contrast to linguistic isolates’ performance on memory as well as semantic tests: they could easily remember hundreds of newly learned words and identify previously seen objects by name. The lack of syntactic language comprehension in linguistic isolates may stem from inability to understand words and/or grammar or inability to mentally synthesize known objects into novel configurations. We have previously shown that purposeful construction of novel mental images is the function of the lateral prefrontal cortex (LPFC) ability to dynamically control posterior cortex neurons1. Here we have ranked all tests performed on linguistic isolates by their reliance on the LPFC control of the posterior cortex: a) the amount of posterior cortex territory that needs to be recruited by the LPFC and b) the number of disparate objects that have to be combined together by the LPFC in order to answer the test question. According to our analysis, linguistic isolates performed well in all tests that did not involve the LPFC control of the posterior cortex, showed decreasing scores in tests that involved greater recruitment of the posterior cortex by the LPFC, and failed in tests that involved greatest recruitment of posterior cortex necessary for mental synthesis of multiple objects. This pattern is consistent with inadequate frontoposterior connections in linguistic isolates. We discuss implications of these findings for the importance of early syntactic language exposure in formation of frontoposterior connections.
Enhancing the Representational Similarity Between Execution and Imagination of Movement Using Network-Based Brain Computer Interfacing
Authors: Kordjazi Neda , Koravand Amineh , Sveistrup Heidi
Published: July 2017

Motor imagery-based brain computer interfacing (MI-BCI) as a neuro-rehabilitation tool aims at facilitating motor improvement using mental practice. However, the effectiveness of MI-BCI in producing clinically meaningful functional outcome is debated. Aside from computational shortcomings, a main limiting obstacle seems to be the substantial representational dissimilarity between movement imagination (MI) and movement execution (ME) on the level of engaged neural networks. This dissimilarity renders inducing functionally effective and long lasting changes in motor behavior through MI challenging. Moreover, the quality and intensity of imagination is highly prone to change on a trial-to-trial basis, based on the subject's state of mind and mental fatigue. This leads to an inconsistent profile of neural activity throughout training, limiting learning in a Hebbian sense. To address these issues, we propose a neuroconnectivity-based paradigm, as a systematic priming technique to be utilized pre-BCI training. In the proposed paradigm, ME-idle representational dissimilarity network (RDN) features are used to detect MI in real-time. This means that to drive the virtual environment, an ME-like activation pattern has to be learned and generated in the brain through MI. This contrasts with conventional BCIs which consider a successful MI, one that results in higher than a threshold change in the power of sensorimotor rhythms. Our results show that four out of five participants achieved a consistent session-to-session enhancement in their net MI-ME network-level similarity (mean change rate of 6.16% ± 4.64 per session). We suggest that the proposed paradigm, if utilized as a priming technique pre-BCI training, can potentially enhance the neural and functional effectiveness. This can be achieved through 1- shifting MI towards engaging ME-related networks to a higher extent, and 2- inducing consistency in MI quality by using the ME-related networks as the ground-truth and thus enhancing the robustness of the activity pattern in the brain. This would in turn lend to the clinical acceptability of BCI as a neurorehabilitation tool.
When the ostrich-algorithm fails: Blanking method affects spike train statistics
Authors: Mottaghi Soheil , Joseph Kevin , Christ Olaf , Feuerstein Thomas J. , Hofmann Ulrich G.
Published: July 2017

1.

Electrophysiological recordings of neuronal tissue face particular challenges when attempted during electrical stimulation, both in vivo and in vitro. Electrical stimulation may produce undesired electronic artifacts and thus render the recorded signal only partially useful. A commonly used remedy for these artifacts is to temporarily ground the input during the stimulation pulses. In the following study, we quantify the effects of this method on the spike train count, which is called "blanking". Starting a from theoretical standpoint, we deduce a loss of countable action potentials, depending on: width of the blanking window, Frequency of stimulation and neuronal activity. Calculations are corroborated by actual high SNR single cell recordings. We have to state, for therapeutically relevant frequencies of 130 Hz and realistic blanking windows of 2 ms, up to 27% of actual existing spikes are lost. We strongly advice careful and controlled use of blanking circuits when spike rate quantification is attempted.
PaSD-qc: Quality control for single cell whole-genome sequencing data using power spectral density estimation
Authors: Sherman Maxwell A. , Barton Alison R. , Lodato Michael , Vitzthum Carl , Coulter Michael E. , Walsh Christopher A. , Park Peter J.
Published: July 2017

Single cell whole-genome sequencing (scWGS) is providing novel insights into the nature of genetic heterogeneity in normal and diseased cells. However, scWGS introduces DNA amplification-related biases that can confound downstream analysis. Here we present a statistical method, with an accompanying package PaSD-qc (PowerSpectralDensity-qc), that evaluates the quality of single cell libraries. It uses a modified power spectral density to assess amplification uniformity, amplicon size distribution, autocovariance, and inter-sample consistency as well as identifies aberrantly amplified chromosomes. We demonstrate the usefulness of this tool in evaluating scWGS protocols and in selecting high-quality libraries from low-coverage data for deep sequencing.
Identification of 55,000 Replicated DNA Methylation QTL
Authors: McRae Allan F , Marioni Riccardo E , Shah Sonia , Yang Jian , Powell Joseph E. , Harris Sarah E , Gibson Jude , Henders Anjali K , Bowdler Lisa , Painter Jodie N. , Murphy Lee , Martin Nicholas G , Starr John M , Wray Naomi R , Deary Ian J , Visscher Peter M , Montgomery Grant W
Published: July 2017

DNA methylation plays an important role in the regulation of transcription. Genetic control of DNA methylation is a potential candidate for explaining the many identified SNP associations with disease that are not found in coding regions. We replicated 52,916cisand 2,025transDNA methylation quantitative trait loci (mQTL) using methylation measured on Illumina HumanMethylation450 arrays in the Brisbane Systems Genetics Study (n=614 from 177 families) and the Lothian Birth Cohorts of 1921 and 1936 (combined n = 1366). ThetransmQTL SNPs were found to be over-represented in 1Mbp subtelomeric regions, and on chromosomes 16 and 19. There was a significant increase intransmQTL DNA methylation sites in upstream and 5’ UTR regions. No association was observed between either the SNPs or DNA methylation sites oftransmQTL and telomere length. The genetic heritability of a number of complex traits and diseases was partitioned into components due to mQTL and the remainder of the genome. Significant enrichment was observed for height (p = 2.1x10−10), ulcerative colitis (p = 2x10−5), Crohn’s disease (p = 6x10−8) and coronary artery disease (p = 5.5x10−6) when compared to a random sample of SNPs with matched minor allele frequency, although this enrichment is explained by the genomic location of the mQTL SNPs.
Spatiotemporal DNA Methylome Dynamics of the Developing Mammalian Fetus
Authors: He Yupeng , Hariharan Manoj , Gorkin David U. , Dickel Diane E. , Luo Chongyuan , Castanon Rosa G. , Nery Joseph R. , Lee Ah Young , Williams Brian A. , Trout Diane , Amrhein Henry , Fang Rongxin , Chen Huaming , Li Bin , Visel Axel , Pennacchio Len A. , Ren Bing , Ecker Joseph R.
Published: July 2017

Genetic studies have revealed an essential role for cytosine DNA methylation in mammalian development. However, its spatiotemporal distribution in the developing embryo remains obscure. Here, we profiled the methylome landscapes of 12 mouse tissues/organs at 8 developmental stages spanning from early embryogenesis to birth. Indepth analysis of these spatiotemporal epigenome maps systematically delineated ~2 million methylation variant regions and uncovered widespread methylation dynamics at nearly one-half million tissue-specific enhancers, whose human counterparts were enriched for variants involved in genetic diseases. Strikingly, these predicted regulatory elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. Accumulation of non-CG methylation within gene bodies of key developmental transcription factors coincided with their transcriptional repression during later stages of fetal development. These spatiotemporal epigenomic maps provide a valuable resource for studying gene regulation during mammalian tissue/organ progression and for pinpointing regulatory elements involved in human developmental diseases.
Computational Foundations of Natural Intelligence
Authors: van Gerven Marcel
Published: July 2017

New developments in AI and neuroscience are revitalizing the quest to understanding natural intelligence, offering insight about how to equip machines with human-like capabilities. This paper reviews some of the computational principles relevant for understanding natural intelligence and, ultimately, achieving strong AI. After reviewing basic principles, a variety of computational modeling approaches is discussed. Subsequently, I concentrate on the use of artificial neural networks as a framework for modeling cognitive processes. This paper ends by outlining some of the challenges that remain to fulfill the promise of machines that show human-like intelligence.
Limited genetic variation for male mating success reveals low evolutionary potential for thermal plasticity inDrosophila melanogaster
Authors: Waller John T. , Kell Anna , Ballesta Mireia , Giraud Aude , Abbott Jessica K. , Svensson Erik I.
Published: July 2017

Populations respond to novel environmental challenges either through genetic changes, through adaptive phenotypic plasticity for the traits in question, or by a combination of these factors. Here, we investigated the evolutionary potential of phenotypic plasticity for male mating success, locomotory ability, and heating rate (a physiological performance trait) in the fruitflyDrosophila melanogaster, using isogenic male lines from the Drosophila Reference Genome Panel (DGRP) and hemi-clonal males. We quantified thermal reaction norms of how male mating success changed in relation to a temperate gradient, ranging from cold (18 °C) via optimal (24 °C) to hot and stressful environments (either 30 °C or 36 °C). We found significant differences in male mating success and locomotory performance between different lines, as well as significant main effects of temperature, but no significant genotype-by-environment interactions (GEI:s). A statistical power analysis revealed that the variance explained by GEI:s for thermal plasticity using this sample size is likely to be modest or very small, and represent only 4% of the total variation in male mating success. The lack of strong GEI:s for these two behavioral traits contrast with the presence of significant GEI:s for male heating rate, as measured by thermal imaging (infrared camera technology). These results suggest that sexual selection through male mating success is not likely to be efficient in mediating evolutionary rescue through changed plasticity in response to changing temperatures.
Fast and memory-efficient noisy read overlapping with KD-trees
Authors: Parkhomchuk Dmitri , Bremges Andreas , McHardy Alice C.
Published: July 2017

Motivation

Third-generation sequencing technologies produce long, but noisy reads with increasing sequencing throughput and decreasing per-base costs. Detecting read-to-read overlaps in such data is the most computationally intensive step inde novoassembly. Recently, efficient algorithms were developed for this task; nearly all of these utilize longk-mers (>10 bp) to compare reads, but vary in their approaches to indexing, hashing, filtering, and dimensionality reduction.

Results

We describe an algorithm for efficient overlap detection that directly compares the full spectrum of shortk-mers, namely tetramers, through geometric embedding and approximate nearest neighbor search in multidimensional KD-trees. A proof of concept implementation detected read-to-read overlaps in bacterial PacBio and ONT datasets with notably lower memory consumption than state-of-the-art approaches and allowed downstreamde novoassembly into single contigs. We also introduce a sequence-context dependent tagging scheme that contributes to memory and computational efficiency and could be used with other aligning and overlapping algorithms.

Availability

A C++14 implementation is available under the open source Apache License 2.0 at:https://github.com/dzif/kd-tree-overlapper
Chromatin loop anchors are associated with genome instability in cancer and recombination hotspots in the germline
Authors: Kaiser Vera B , Semple Colin A
Published: July 2017

Chromatin loops form a basic unit of interphase nuclear organisation, providing contacts between regulatory regions and target promoters, and forming higher level patterns defining self interacting domains. Recent studies have shown that mutations predicted to alter chromatin loops and domains are frequently observed in tumours and can result in the upregulation of oncogenes, but the combinations of selection and mutational bias underlying these observations remains unknown. Here, we explore the unusual mutational landscape associated with chromatin loop anchor points (LAPs), which are located at the base of chromatin loops and form a kinetic trap for cohesin. We show that LAPs are strongly depleted for single nucleotide variants (SNVs) in tumours, which is consistent with their relatively early replication timing. However, despite low SNV rates, LAPs emerge as sites of evolutionary innovation showing enrichment for structural variants (SVs). They harbour an excess of SV breakpoints in cancers, are prone to double strand breaks in somatic cells, and are bound by DNA repair complex proteins. Recurrently disrupted LAPs are often associated with genes annotated with functions in cell cycle transitions. An unexpectedly large fraction of LAPs (16%) also overlap known meiotic recombination hotspot (HSs), and are enriched for the core PRDM9 binding motif, suggesting that LAPs have been foci for diversity generated during recent human evolution. We suggest that the unusual chromatin structure at LAPs underlies the elevated SV rates observed, marking LAPs as sites of regulatory importance but also genomic fragility.
BAF chromatin remodeling complex subunit diversity promotes temporally distinct gene expression programs in cardiogenesis
Authors: Hota Swetansu K. , Johnson Jeffrey R. , Verschueren Erik , Thomas Reuben , Blotnick Aaron M. , Zhu Yiwen , Sun Xin , Pennacchio Len A. , Krogan Nevan J. , Bruneau Benoit G.
Published: July 2017

Chromatin remodeling complexes instruct cellular differentiation and lineage specific transcription. The BRG1/BRM associated factor (BAF) complexes are important for several aspects of differentiation. We show that the catalytic subunitBrg1has a specific role in cardiac precursors (CPs) to initiate cardiac gene expression programs and repress non-cardiac expression. Using immunoprecipitation with mass spectrometry (IP-MS), we determined the dynamic composition of BAF complexes during mammalian cardiac differentiation, and identified BAF60c (SMARCD3) and BAF170 (SMARCC2) as subunits enriched in CPs and cardiomyocytes (CM).Baf60candBaf170co-regulate gene expression withBrg1in CPs, but in CMs control different gene expression programs, although still promoting a cardiac-specific gene set. BRG1, BAF60, and BAF170 all modulate chromatin accessibility, to either promote accessibility at activated genes, while closing up chromatin at repressed genes. BAF60c and BAF170 are required for proper BAF complex composition and stoichiometry, and promote BRG1 occupancy in CM. Additionally, BAF170 facilitates expulsion of BRG1-containing complexes in the transition from CP to CM. Thus, dynamic interdependent BAF complex subunit assembly modulates chromatin states and thereby directs temporal gene expression programs in cardiogenesis.

Significance statement

BRG1/BRM associated factors (BAF) form multi-subunit protein complexes that reorganize chromatin and regulate transcription. Specific BAF complex subunits have important roles during cell differentiation and development. We systematically identify BAF subunit composition and find temporal enrichment of subunits during cardiomyocyte differentiation. We find the catalytic subunit BRG1 has important contributions in initiating gene expression programs in cardiac progenitors along with cardiac-enriched subunits BAF60c and BAF170. Both these proteins regulated BAF subunit composition and chromatin accessibility and prevent expression of non-cardiac developmental genes during precursor to cardiomyocyte differentiation. Mechanistically, we find BAF170 destabilizes the BRG1 complex and expels BRG1 from cardiomyocyte-specific genes. Thus, our data shows synergies between diverse BAF subunits in facilitating temporal gene expression programs during cardiogenesis.
Developmental transcriptomics of the brittle starAmphiura filiformisreveals gene regulatory network rewiring in echinoderm larval skeleton evolution
Authors: Dylus David , Blowes Liisa M. , Czarkwiani Anna , Elphick Maurice R. , Oliveri Paola
Published: July 2017

Amongst the echinoderms the class Ophiuroidea is of particular interest for its phylogenetic position, ecological importance, developmental and regenerative biology. However, compared to other echinoderms, notably echinoids (sea urchins), relatively little is known about developmental changes in gene expression in ophiuroids. To address this issue we have generated and assembled a large RNAseq data set of four key stages of development in the brittle starAmphiura filiformisand ade novoreference transcriptome of comparable quality to that of a model echinoderm - the sea urchinStrongyloncentrotus purpuratus. Furthermore, we provide access to the new data via a web interface:http://www.echinonet.eu/shiny/Amphiura_filiformis/. With a focus on skeleton development, we have identified highly conserved genes associated with the development of a biomineralized skeleton. We also identify important class-specific characters, including the independent duplication of themsp130class of genes in different echinoderm classes and the unique occurrence of spicule matrix (sm) genes in echinoids. Using a new quantification pipeline for ourde novotranscriptome, validated with other methodologies, we find major differences between brittle stars and sea urchins in the temporal expression of many transcription factor genes. This divergence in developmental regulatory states is more evident in early stages of development when cell specification begins, than when cells initiate differentiation. Our findings indicate that there has been a high degree of gene regulatory network rewiring in the evolution of echinoderm larval development.

Data Depositions

All sequence reads are available at Genbank SRR4436669 - SRR4436674. Any sequence alignments used are available by the corresponding author upon request.
Using MinION™to characterize dog skin microbiota through full-length 16S rRNA gene sequencing approach
Authors: Cuscó Anna , Viñes Joaquim , D’Andreano Sara , Riva Francesca , Casellas Joaquim , Sánchez Armand , Francino Olga
Published: July 2017

The most common strategy to assess microbiota is sequencing specific hypervariable regions of 16S rRNA gene using 2ndgeneration platforms (such as MiSeq or Ion Torrent PGM). Despite obtaining high-quality reads, many sequences fail to be classified at the genus or species levels due to their short length. This pitfall can be overcome sequencing the full-length 16S rRNA gene (1,500bp) by 3rdgeneration sequencers.

We aimed to assess the performance of nanopore sequencing using MinION™on characterizing microbiota complex samples. First set-up step was performed using a staggered mock community (HM-783D). Then, we sequenced a pool of several dog skin microbiota samples previously sequenced by Ion Torrent PGM. Sequences obtained for full-length 16S rRNA with degenerated primers retrieved increased richness estimates at high taxonomic level (Bacteria and Archaea) that were missed with short-reads. Besides, we were able to obtain taxonomic assignments down to species level, although it was not always feasible due to: i) incomplete database; ii) primer set chosen; iii) low taxonomic resolution of 16S rRNA gene within some genera; and/or iv) sequencing errors. Nanopore sequencing of the full-length 16S rRNA gene using MinION™with 1D sequencing kit allowed us inferring microbiota composition of a complex microbial community to lower taxonomic levels than short-reads from 2ndgeneration sequencers.
Multiple Geographical Origins of Environmental Sex Determination enhanced the diversification of Darwin’s Favourite Orchids
Authors: Pérez-Escobar Oscar Alejandro , Chomicki Guillaume , Condamine Fabien L. , de Vos Jurriaan M. , Martins Aline C. , Smidt Eric C. , Klitgård Bente , Gerlach Günter , Heinrichs Jochen
Published: July 2017

Environmental sex determination (ESD) – a change in sexual function during an individual life span driven by environmental cues – is an exceedingly rare sexual system among angiosperms. Because ESD can directly affect reproduction success, it could influence diversification rate as compared with lineages that have alternative mating systems. Here we test this hypothesis using a solid phylogenetic framework of Neotropical Catasetinae, the angiosperm lineage richest in taxa with ESD. We assess whether gains of ESD are associated with higher diversification rates compared to lineages with alternative systems while considering additional traits known to positively affect diversification rates in orchids. We found that ESD has evolved asynchronously three times during the last ~5 Myr. Lineages with ESD have consistently higher diversification rates than related lineages with other sexual systems. Habitat fragmentation due to mega-wetlands extinction, and climate instability are suggested as the driving forces for ESD evolution.
Understanding the dynamics of scaffold-mediated signaling
Authors: Suderman Ryan , Schauer Addison , Deeds Eric J.
Published: July 2017

Many signaling networks involve scaffold proteins that bind multiple kinases in kinase cascades. While scaffolds play a fundamental role in regulating signaling, few hypotheses regarding their function have been rigorously examined. Here, we used dynamical models of scaffold signaling to investigate the impact scaffolds have on network behavior. We considered two paradigms of scaffold assembly: as either the nucleation point for assembly of discrete multi-subunit proteins (the machine paradigm) or a platform upon which kinases independently associate (the ensemble paradigm). We found that several well-accepted hypotheses regarding the role of scaffolds in regulating signal response either do not hold or depend critically on the assembly paradigm employed. In addition to providing novel insights into the function of scaffold proteins, our work suggests experiments that could distinguish between assembly paradigms. Our findings should also inform attempts to target scaffold proteins for therapeutic intervention and the design of scaffolds for synthetic biology.
Distinct antibody-mediated selection in a narrow-source HIV-1 outbreak among Chinese former plasma donors
Authors: Andrews Sophie M. , Zhang Yonghong , Dong Tao , Rowland-Jones Sarah L. , Gupta Sunetra , ESBJÖRNSSON Joakim
Published: July 2017

The HIV-1 envelope protein mutates rapidly to evade recognition and killing, and is a major target of the humoral immune response and in vaccine development. Identification of common antibody epitopes for vaccine development have been complicated by large variations on both virus (different infecting founder strains) and host genetic levels. We studied HIV-1 envelopegp120evolution in 12 Chinese former plasma donors infected with a purportedly single founder virus, with the aim of identifying common antibody epitopes under immune selection. We found five amino acid sites to be under significant positive selection in ≥50% of the patients, and 22 sites housing mutations consistent with antibody-mediated selection. Despite strong selection pressure, some sites housed a limited repertoire of amino acids. Structural modelling revealed that most sites were located on the exposed distal edge of the Gp120 trimer, whilst wholly invariant sites clustered within the centre of the protein complex. Four sites, flanking the V3 hypervariable loop of the Gp120, represent novel antibody epitopes that may be suitable as vaccine candidates.