bluuebunny/crossref_metadata_2025 huggingface dataset:
Is strength‐training frequency a key factor to develop performance adaptations in young elite soccer players?
Authors: Otero‐Esquina Carlos , de Hoyo Lora Moisés , Gonzalo‐Skok Óliver , Domínguez‐Cobo Sergio , Sánchez Hugo
Published: September 2017

The aim of this study was to analyse the effects of a combined strength‐training programme (full‐back squat, YoYoTM leg curl, plyometrics and sled towing exercises) on performance in elite young soccer players and to examine the effects when this training programme was performed one or two days per week. Thirty‐six male soccer players (U‐17 to U‐19) were recruited and assigned to experimental groups (EXP1: 1 s w−1; EXP2: 2 s w−1) or a control group (CON). Performance was assessed through a countermovement jump (CMJ) test (relative peak power [CMJPP] and CMJ height [CMJH]), a 20‐m linear sprint test with split‐times at 10‐m, and a change of direction test (V‐cut test) 1 week before starting the training programme and also 1 week after performing such training programme. Within‐group analysis showed substantial improvements in CMJ variables (ES: 0.39–0.81) and COD (ES: 0.70 and 0.76) in EXP1 and EXP2, while EXP2 also showed substantial enhancements in all linear sprinting tests (ES: 0.43–0.52). Between‐group analysis showed substantially greater improvements in CMJ variables (ES: 0.39–0.68) in experimental groups in comparison to CON. Furthermore, EXP2 achieved a substantial better performance in 20‐m (ES: 0.48–0.64) than EXP1 and CON. Finally, EXP2 also showed greater enhancements in 10‐m (ES: 0.50) and V‐cut test (ES: 0.52) than EXP1. In conclusion, the combined strength‐training programme improved jumping ability, independently of training frequency, though the achievement of two sessions per week also enhanced sprinting abilities (linear and COD) in young soccer players.
Proxy Pasts: The Use of British Historical References in Spanish American Independence Rhetoric, 1808–1828
Authors: Racine Karen
Published: September 2017

In the independence era of the early nineteenth century, Spanish American patriot leaders hoped to find in Great Britain an ally not only in their fight for emancipation, but also in their efforts to become accepted into the family of nations. To do this, they not only cast their eyes across land and sea to study what contemporary Britain might offer as a political model, but they also ransacked the history books for material from its past. Although it is commonly assumed that the American and French Revolutions were the inspirations for Spanish American independence leaders, a strong case can be made for their attraction to the British model and historical experience. Their newspapers and congressional debates were filled with discussions of Magna Carta, the Tudors and Stuarts, the Armada, Oliver Cromwell and the English Civil War, all of which were deployed with great skill to inform contemporary debates on matters such as religious tolerance, the jury system, the relative merits of republics versus monarchies, and the role of strong women in public life. The extensive use of British historical references reveals much about a political model that was attracting serious consideration during the Spanish American independence period.
FACETS: using open data to measure community social determinants of health
Authors: Cantor Michael N , Chandras Rajan , Pulgarin Claudia
Published: September 2017

Objective

To develop a dataset based on open data sources reflective of community-level social determinants of health (SDH).

Materials and Methods

We created FACETS (Factors Affecting Communities and Enabling Targeted Services), an architecture that incorporates open data related to SDH into a single dataset mapped at the census-tract level for New York City.

Results

FACETS (https://github.com/mcantor2/FACETS) can be easily used to map individual addresses to their census-tract-level SDH. This dataset facilitates analysis across different determinants that are often not easily accessible.

Discussion

Wider access to open data from government agencies at the local, state, and national level would facilitate the aggregation and analysis of community-level determinants. Timeliness of updates to federal non-census data sources may limit their usefulness.

Conclusion

FACETS is an important first step in standardizing and compiling SDH-related data in an open architecture that can give context to a patient’s condition and enable better decision-making when developing a plan of care.
Reinforcing the Mucoperiosteal Pocket with the Scarpa Fascia Graft in Secondary Alveolar Bone Grafting: A Retrospective Controlled Outcome Study
Authors: Lonic Daniel , Yamaguchi Kazuaki , Chien-Jung Pai Betty , Lo Lun-Jou
Published: September 2017

Background:

Secondary alveolar bone grafting is the gold standard for the treatment of alveolar clefts in cleft lip and palate patients. The authors present a modified method using a Scarpa fascia graft that is placed deep into the mucoperiosteal pocket for watertight sealing of the bone graft chamber and limiting the graft position to the alveolar region for bony stability and tooth support. The outcome was assessed for clinical success in terms of bone graft stability and infection rate.

Methods:

Seventy-four unilateral complete cleft lip and palate patients were enrolled in this retrospective study consisting of equal-size Scarpa fascia and control groups of consecutive unilateral complete cleft lip and palate patients undergoing secondary alveolar bone grafting. Occlusal radiographs of the alveolar cleft taken at least 1 year postoperatively were evaluated for Spearman correlated Bergland and Witherow scales. Statistical evaluation was conducted using t test, chi-square test, and odds ratio.

Results:

The clinical success rate (Bergland types I and II) of the Scarpa fascia procedure was significantly higher (67.6 versus 94.6 percent, respectively), with a significantly lower infection rate (16.2 versus 2.7 percent, respectively) and a high correlation of Bergland and Witherow scales (0.964; p < 0.001). There was no wound dehiscence, fistula, bone graft exposure, or additional donor-site morbidity in the Scarpa fascia group.

Conclusion:

The authors’ new method of alveolar bone grafting with the Scarpa fascia graft is safe and effective, and has one of the highest documented success rates.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Olfactory sensation promotes social motivation in the mouse.
Authors: Kuo Tsung-Han , Dey Sandeepa , Koblesky Norah , Mukhopadhyay Sourish , Stowers Lisa
Published: September 2017

Previous experience within an environment can influence subsequent behavior; however, what makes one strive for social dominance or capitulate to subordinance in a novel environment? Here we find motor output of socially unequal participants in a new situation indistinguishable: with winners only differing by extending social motivation which depends on olfactory sensation. Our study provides a simple platform to identify the mechanisms underlying sensory processing and social motivation.
Unliganded Progesterone Receptor Governs Estrogen Receptor Gene Expression by Regulating DNA Methylation in Breast Cancer Cells
Authors: Verde Gaetano , De Llobet Lara I. , Wright Roni H.G. , Quilez Javier , Peiró Sandra , Dily François Le , Beato Miguel
Published: September 2017

Breast cancer prognosis and response to endocrine therapy strongly depends on the expression of the estrogen and progesterone receptors (ER and PR, respectively). Although much is known about ERαgene (ESR1) regulation after hormonal stimulation, how it is regulated in hormone-free condition is not fully understood. We used ER-/PR-positive breast cancer cells to investigate the role of PR inESR1regulation in the absence of hormones. We show that PR binds to the low-methylatedESR1promoter and maintains both gene expression and DNA methylation of the ESR1 locus in hormone-deprived breast cancer cells. Depletion of PR reducesESR1expression, with a concomitant increase in gene promoter methylation. The high amount of methylation in theESR1promoter of PR-depleted cells persists after the stable re-expression of PR and inhibits PR binding to this genomic region. As a consequence, the rescue of PR expression in PR-depleted cells is insufficient to restoreESR1expression. Consistently, DNA methylation impedes PR binding to consensus progesterone responsive elements. These findings contribute to understanding the complex crosstalk between PR and ER and suggest that the analysis ofESR1promoter methylation in breast cancer cells can help to design more appropriate targeted therapies for breast cancer patients.
Characterization and Validation of a Novel Group of Type V, Class 2 Nucleases forin vivoGenome Editing
Authors: Begemann Matthew B. , Gray Benjamin N. , January Emma , Singer Anna , Kesler Dylan C. , He Yonghua , Liu Haijun , Guo Hongjie , Jordan Alex , Brutnell Thomas P. , Mockler Todd C. , Oufattole Mohammed
Published: September 2017

CRISPR-based genome editing is an enabling technology with potential to dramatically transform multiple industries. Identification of additional editing tools will be imperative for broad adoption and application of this technology. A novel Type V, Class 2 CRISPR nuclease system was identified fromMicrogenomatesandSmithellabacterial species (CRISPR fromMicrogenomatesandSmithella, Cms1). This system was shown to efficiently generate indel mutations in the major crop plant rice (Oryza sativa). Cms1 are distinct from other Type V nucleases, are smaller than most other CRISPR nucleases, do not require a tracrRNA, and have an AT-rich protospacer-adjacent motif site requirement. A total of four novel Cms1 nucleases across multiple bacterial species were shown to be functional in a eukaryotic system. This is a major expansion of the Type V CRISPR effector protein toolbox and increases the diversity of options available to researchers.
Effective reserve: a latent variable to improve outcome prediction in stroke
Authors: Schirmer Markus D. , Etherton Mark R. , Dalca Adrian V. , Giese Anne-Katrin , Cloonan Lisa , Wu Ona , Golland Polina , Rost Natalia S.
Published: September 2017

Background

Prediction of functional outcome after stroke based on initial presentation remains an open challenge, suggesting that an important aspect is missing from these prediction models. There exists the notion of a protective mechanism called brain reserve, which may be utilized to understand variations in disease outcome. In this work we expand the concept of brain reserve (effective reserve) to improve prediction models of functional outcome after acute ischemic stroke (AIS).

Methods

Consecutive AIS patients with acute brain MRI (<48 hours) were eligible for this study. White matter hyperintensity and acute infarct volume were determined on T2 fluid attenuated inversion recovery and diffusion weighted images, respectively. Modified Rankin Scale scores (mRS) were obtained at 90 days post-stroke. Effective reserve (eR) was defined as a latent variable using structural equation modeling by including age, systolic blood pressure, and intracranial volume measurements.

Results

Of 453 AIS patients (mean age 66.6±14.7 years), 36% were male and 311 hypertensive. There was inverse association between eR and 90-day mRS (path coefficient -0.18±0.01, p<0.01). As compared to a model without eR, correlation between predicted mRS and observed mRS improved in the eR-based model (Spearman’s ρ 0.29±0.18 versus 0.15±0.17, p<0.001). Furthermore, hypertensive patients exhibited lower eR (p<10−6).

Conclusion

Using eR in prediction models of stroke outcome is feasible and leads to better model performance. Furthermore, higher eR is associated with more favorable functional post-stoke outcome and might correspond to an overall better vascular health.
Strelka2: Fast and accurate variant calling for clinical sequencing applications
Authors: Kim Sangtae , Scheffler Konrad , Halpern Aaron L , Bekritsky Mitchell A , Noh Eunho , Källberg Morten , Chen Xiaoyu , Beyter Doruk , Krusche Peter , Saunders Christopher T
Published: September 2017

We describe Strelka2 (https://github.com/Illumina/strelka), an open-source small variant calling method for clinical germline and somatic sequencing applications. Strelka2 introduces a novel mixture-model based estimation of indel error parameters from each sample, an efficient tiered haplotype modeling strategy and a normal sample contamination model to improve liquid tumor analysis. For both germline and somatic calling, Strelka2 substantially outperforms current leading tools on both variant calling accuracy and compute cost.
A plasmid-basedEscherichia coligene expression system with cell-to-cell variation below the extrinsic noise limit
Authors: Hensel Zach
Published: September 2017

Experiments in synthetic biology and microbiology can benefit from protein expression systems with low cell-to-cell variability (noise) and expression levels precisely tunable across a useful dynamic range. Despite advances in understanding the molecular biology of microbial gene regulation, many experiments employ protein-expression systems exhibiting high noise and nearly all-or-none responses to induction. I present an expression system that incorporates elements known to reduce gene expression noise: negative autoregulation and bicistronic transcription. I show by stochastic simulation that while negative autoregulation can produce a more gradual response to induction, bicistronic expression of a repressor and gene of interest can be necessary to reduce noise below the extrinsic limit. I synthesized a plasmid-based system incorporating these principles and studied its properties inEscherichia colicells, using flow cytometry and fluorescence microscopy to characterize induction dose-response, induction/repression kinetics and gene expression noise. By varying ribosome binding site strengths, expression levels from 55— 10,740 molecules/cell were achieved with noise below the extrinsic limit. Individual strains are inducible across a dynamic range greater than 20-fold. Experimental comparison of different regulatory networks confirmed that bicistronic autoregulation reduces noise, and revealed unexpectedly high noise for a conventional expression system with a constitutively expressed transcriptional repressor. I suggest a hybrid, low-noise expression system to increase the dynamic range.
Filling Gaps in Bacterial Amino Acid Biosynthesis Pathways with High-throughput Genetics
Authors: Price Morgan N. , Zane Grant M. , Kuehl Jennifer V. , Melnyk Ryan A. , Wall Judy D. , Deutschbauer Adam M. , Arkin Adam P.
Published: September 2017

For many bacteria with sequenced genomes, we do not understand how they synthesize some amino acids. This makes it challenging to reconstruct their metabolism, and has led to speculation that bacteria might be cross-feeding amino acids. We studied heterotrophic bacteria from 10 different genera that grow without added amino acids even though an automated tool predicts that the bacteria have gaps in their amino acid synthesis pathways. Across these bacteria, there were 11 gaps in their amino acid biosynthesis pathways that we could not fill using current knowledge. Using genome-wide mutant fitness data, we identified novel enzymes that fill 9 of the 11 gaps and hence explain the biosynthesis of methionine, threonine, serine, or histidine by bacteria from six genera. We also found that the sulfate-reducing bacteriumDesulfovibrio vulgarissynthesizes homocysteine (which is a precursor to methionine) by using DUF39, NIL/ferredoxin, and COG2122 proteins, and that homoserine is not an intermediate in this pathway. Our results suggest that most free-living bacteria can likely make all 20 amino acids and illustrate how high-throughput genetics can uncover previously-unknown amino acid biosynthesis genes.
Microglia from offspring of dams with allergic asthma exhibit epigenomic alterations in genes dysregulated in autism
Authors: Ciernia Annie Vogel , Careaga Milo , LaSalle Janine , Ashwood Paul
Published: September 2017

Dysregulation in immune responses during pregnancy increase the risk of a having a child with an autism spectrum disorder (ASD). Asthma is one of the most common chronic diseases among pregnant women, and symptoms often worsen during pregnancy. We recently developed a mouse model of maternal allergic asthma (MAA) that induces changes in sociability, repetitive and perseverative behaviors in the offspring. Since epigenetic changes help a static genome adapt to the maternal environment, activation of the immune system may epigenetically alter fetal microglia, the brain’s resident immune cells. We therefore tested the hypothesis that epigenomic alterations to microglia may be involved in behavioral abnormalities observed in MAA offspring. We used the genome-wide approaches of whole genome bisulfite sequencing to examine DNA methylation and RNA sequencing to examine gene expression in microglia from juvenile MAA offspring. Differentially methylated regions (DMRs) were enriched for immune signaling pathways and important microglial developmental transcription factor binding motifs. Differential expression analysis identified genes involved in controlling microglial sensitivity to the environment and shaping neuronal connections in the developing brain. Differentially expressed associated genes significantly overlapped genes with altered expression in human ASD cortex, supporting a role for microglia in the pathogenesis of ASD.

Main Points:

Maternal allergic asthma induces changes in DNA methylation and transcription in juvenile offspring microglia

Differentially methylated regions are enriched for functions and transcription factor binding motifs involved in inflammation and microglial development

Differentially expressed genes and differentially methylated regions are enriched for genes dysregulated in Autism Spectrum Disorders
Long-term cardiovascular re-programming by short-term perinatal exposure to nicotine‘s main metabolite cotinine
Authors: Bastianini Stefano , Martire Viviana Lo , Silvani Alessandro , Zoccoli Giovanna , Berteotti Chiara , Lagercrantz Hugo , Arner Anders , Cohen Gary
Published: September 2017

Background

Cotinine - a nicotine by-product and biomarker of passive perinatal tobacco smoke exposure - is historically considered to lack significant health effects. We challenged this notion and sought “proof-of-concept” evidence of the adverse developmental potential of exposure to this substance at real-life levels.

Methods

Pregnant C57 mice drank nicotine or cotinine-laced water for 6wks from conception (NPRE= 2% saccharin+100μg nicotine/ml; CPRE= 2% saccharin + 10μg cotinine/ml) or for 3wks after birth (CPOST= 2% saccharin + 30μg cotinine/ml). Controls drank 2% saccharin (CTRL). At 17±1weeks male pups (CTRL n=6; CPOSTn=6; CPREn=8; NPREn=9) were instrumented for EEG and blood pressure (BP) telemetry. We evaluated (i) cardiovascular control during sleep (at rest / during stress); (ii) arterial reactivity ex vivo; (iii) expression of genes involved in arterial constriction/dilation.

Results

Blood cotinine levels (ELISA) recapitulated passive smoker mothers-infants. Pups exposed only to cotinine exhibited (i) mild bradycardia - hypotension at rest (p<0.001); (ii) attenuated (CPRE, p<0.0001) or reverse (CPOST; p<0.0001) BP reactivity to asphyxia; (iii) pronounced adrenergic hypo-contractility (p<0.0003), low Protein Kinase C (p<0.001) and elevated adrenergic receptor mRNA (p<0.05) (all drug-treated arteries). NPREpups also exhibited endothelium-mediated dysfunction.

Conclusions

Cotinine has subtle, enduring developmental consequences. Some cardiovascular effects of nicotine can plausibly arise via conversion to cotinine. Low-level exposure to this metabolite may pose unrecognized perinatal risks. Adults must avoid inadvertently exposing a fetus or infant to cotinine as well as nicotine.
Genetic validation of bipolar disorder identified by automated phenotyping using electronic health records
Authors: Chen Chia-Yen , Lee Phil H. , Castro Victor M. , Minnier Jessica , Charney Alexander W. , Stahl Eli A. , Ruderfer Douglas M. , Murphy Shawn N. , Gainer Vivian , Cai Tianxi , Jones Ian , Pato Carlos , Pato Michele , Landén Mikael , Sklar Pamela , Perlis Roy H. , Smoller Jordan W.
Published: September 2017

Bipolar disorder (BD) is a heritable mood disorder characterized by episodes of mania and depression. Although genomewide association studies (GWAS) have successfully identified genetic loci contributing to BD risk, sample size has become a rate-limiting obstacle to genetic discovery. Electronic health records (EHRs) represent a vast but relatively untapped resource for high-throughput phenotyping. As part of the International Cohort Collection for Bipolar Disorder (ICCBD), we previously validated automated EHR-based phenotyping algorithms for BD against in-person diagnostic interviews (Castro et al. 2015). Here, we establish the genetic validity of these phenotypes by determining their genetic correlation with traditionally-ascertained samples. Case and control algorithms were derived from structured and narrative text in the Partners Healthcare system comprising more than 4.6 million patients over 20 years. Genomewide genotype data for 3,330 BD cases and 3,952 controls of European ancestry were used to estimate SNP-based heritability (h2g) and genetic correlation(rg) between EHR-based phenotype definitions and traditionally-ascertained BD cases in GWAS by the ICCBD and Psychiatric Genomics Consortium (PGC) using LD score regression. We evaluated BD cases identified using 4 EHR-based algorithms: an NLP-based algorithm (95-NLP) and 3 rule-based algorithms using codified EHR with decreasing levels of stringency - “coded-strict”, “coded-broad”, and “coded-broad based on a single clinical encounter” (coded-broad-SV). The analytic sample comprised 862 95-NLP, 1,968 coded-strict, 2,581 coded-broad, 408 coded-broad-SV BD cases, and 3,952 controls. The estimated h2gwere 0.24 (p=0.015), 0.09 (p=0.064), 0.13 (p=0.003), 0.00 (p=0.591) for 95-NLP, coded-strict, coded-broad and coded-broad-SV BD, respectively. The h2gfor all EHR-based cases combined except coded-broad-SV (excluded due to 0 h2g) was 0.12 (p=0.004). These h2gwere lower or similar to the h2gobserved by the ICCBD+PGCBD (0.23, p=3.17E-80, total N=33,181). However, the rgbetween ICCBD+PGCBD and the EHR-based cases were high for 95-NLP (0.66, p=3.69x10-5), coded-strict (1.00, p=2.40x10-4), and coded-broad (0.74, p=8.11x10-7). The rgbetween EHR-based BDs ranged from 0.90 to 0.98. These results provide the first genetic validation of automated EHR-based phenotyping for BD and suggest that this approach identifies cases that are highly genetically correlated with those ascertained through conventional methods. High throughput phenotyping using the large data resources available in EHRs represents a viable method for accelerating psychiatric genetic research.
Biosensor libraries harness large classes of binding domains for allosteric transcription regulators
Authors: Juárez Javier F. , Lecube-Azpeitia Begoña , Brown Stuart L. , Church George M.
Published: September 2017

Bacteria’s ability to specifically sense small molecules in their environment and trigger metabolic responses in accordance is an invaluable biotechnological resource. While many transcription factors (TFs) mediating these processes have been studied, only a handful has been leveraged for molecular biology applications. To expand this panel of biotechnologically important sensors here we present a strategy for the construction and testing of chimeric TF libraries, based on the fusion of highly soluble periplasmic binding proteins (PBPs) with DNA-binding domains (DBDs). We validated this strategy by constructing and functionally testing two unique sense-and-response regulators for benzoate, an environmentally and industrially relevant metabolite. This work will enable the development of tailored biosensors for synthetic regulatory circuits.
A common pattern of DNase-I footprinting throughout the human mtDNA unveils clues for a chromatin-like organization
Authors: Blumberg Amit , Danko Charles G. , Kundaje Anshul , Mishmar Dan
Published: September 2017

Human mitochondrial DNA (mtDNA) is believed to lack chromatin and histones. Instead, it is coated solely by the transcription factor TFAM, which binds the mtDNA without sequence specificity and packs it into a bacterial-like nucleoid in a dose-dependent fashion. We asked whether mtDNA packaging is more regulated than once thought. As a first step to address this question, we analyzed mtDNA DNase-I-seq experiments in 324 different human cell types and found, for the first time, a pattern of 29 Genomic footprinting (DGF) sites throughout the mtDNA shared by ∼90% of the tested samples. Low SNP density at the DGF sites, and their conservation in mouse DNase-seq experiments, reflect strong selective constraints. Co-localization of the DGFs with known mtDNA regulatory elements and with recently-discovered transcription pausing sites, suggest a role for such DGFs in mtDNA transcription. Altered mtDNA DGF pattern in IL-3 treated CD+34 cells offer first clue to their physiological importance. Taken together, human mtDNA has a conserved and regulated protein-DNA organization, which is likely involved in regulation of mtDNA gene expression.
Structure and function of the intermembrane space domain of mammalian FoF1ATP synthase
Authors: Fischer Niels , Beilsten-Edmands Victoria , Chorev Dror S. , Hauer Florian , Jiko Chimari , Shimada Satoru , Shinzawa-Itoh Kyoko , Robinson Carol V. , Stark Holger , Gerle Christoph
Published: September 2017

Mitochondrial FoF1ATP synthase is a membrane bound molecular machine central to cellular energy conversion and cristae architecture. Recently, a novel domain has been visualized in the intermembrane space region of mammalian ATP synthase. The complete three-dimensional (3D) structure, composition and function of this domain - which we term intermembrane space domain (IMD) - are unknown. Here, we present two distinct 3D structures of monomeric bovine FoF1ATP synthase by single particle cryo-electron microscopy (cryo-EM) that differ by the presence and absence of the IMD. Comparison of both structures reveals the IMD to be a bipartite and weakly associated domain of FoF1ATP synthase. The tubular sub-domain of the IMD appears to contact the rotor-ring region, its globular sub-domain is anchored in the membrane-bending kink of the ATP synthase. However, absence of the IMD does not impact the kink in the transmembrane region ruling out a functional role in membrane bending. By combining our structural analysis with chemical cross-linking and reported biochemical, genetic and structural data we identify 6.8PL and DAPIT as the subunits forming the intermembrane space domain. We compare the present structure of the mammalian IMD in the bovine FoF1ATP synthase monomer with structures of dimeric FoF1ATP synthase from yeast and ciliate showing that the IMD is a common, but structurally divergent feature of several mitochondrial ATP synthases. On the basis of our analysis we discuss potential functions of the novel domain in rotary catalysis, oligomerization and mitochondrial permeability transition.
miRNAgFree: prediction and profiling of novel microRNAs without genome assembly
Authors: Aparicio EL , Rueda A , Fromm B. , Gómez-Martín C , Lebrón R , Oliver JL , Marchal JA , Kotsyfakis M , Hackenberg M
Published: September 2017

The prediction of novel miRNA genes generally requires the availability of genome sequences in order to assess important properties such as the characteristic hairpin-shaped secondary structure. However, although the sequencing costs have decreased over the last years, still many important species lack an assembled genome of certain quality. We implemented an algorithm which for the first time exploits characteristic biogenesis features like the 5’ homogeneity that can be assessed without genome sequences. We used a phylogenetically broad spectrum of well annotated animal genomes for benchmarking. We found that between 90-100% of the most expressed miRNA candidates (top quartile) corresponded to known miRNA sequences.
Multi-platform discovery of haplotype-resolved structural variation in human genomes
Authors: Chaisson Mark J.P. , Sanders Ashley D. , Zhao Xuefang , Malhotra Ankit , Porubsky David , Rausch Tobias , Gardner Eugene J. , Rodriguez Oscar , Guo Li , Collins Ryan L. , Fan Xian , Wen Jia , Handsaker Robert E. , Fairley Susan , Kronenberg Zev N. , Kong Xiangmeng , Hormozdiari Fereydoun , Lee Dillon , Wenger Aaron M. , Hastie Alex , Antaki Danny , Audano Peter , Brand Harrison , Cantsilieris Stuart , Cao Han , Cerveira Eliza , Chen Chong , Chen Xintong , Chin Chen-Shan , Chong Zechen , Chuang Nelson T. , Lambert Christine C. , Church Deanna M. , Clarke Laura , Farrell Andrew , Flores Joey , Galeev Timur , Gorkin David , Gujral Madhusudan , Guryev Victor , Heaton William Haynes , Korlach Jonas , Kumar Sushant , Kwon Jee Young , Lee Jong Eun , Lee Joyce , Lee Wan-Ping , Lee Sau Peng , Li Shantao , Marks Patrick , Viaud-Martinez Karine , Meiers Sascha , Munson Katherine M. , Navarro Fabio , Nelson Bradley J. , Nodzak Conor , Noor Amina , Kyriazopoulou-Panagiotopoulou Sofia , Pang Andy , Qiu Yunjiang , Rosanio Gabriel , Ryan Mallory , Stütz Adrian , Spierings Diana C.J. , Ward Alistair , Welch AnneMarie E. , Xiao Ming , Xu Wei , Zhang Chengsheng , Zhu Qihui , Zheng-Bradley Xiangqun , Lowy Ernesto , Yakneen Sergei , McCarroll Steven , Jun Goo , Ding Li , Koh Chong Lek , Ren Bing , Flicek Paul , Chen Ken , Gerstein Mark B. , Kwok Pui-Yan , Lansdorp Peter M. , Marth Gabor , Sebat Jonathan , Shi Xinghua , Bashir Ali , Ye Kai , Devine Scott E. , Talkowski Michael , Mills Ryan E. , Marschall Tobias , Korbel Jan O. , Eichler Evan E. , Lee Charles
Published: September 2017

The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, and strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three human parent–child trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per human genome. We also discover 156 inversions per genome—most of which previously escaped detection. Fifty-eight of the inversions we discovered intersect with the critical regions of recurrent microdeletion and microduplication syndromes. Taken together, our SV callsets represent a sevenfold increase in SV detection compared to most standard high-throughput sequencing studies, including those from the 1000 Genomes Project. The method and the dataset serve as a gold standard for the scientific community and we make specific recommendations for maximizing structural variation sensitivity for future large-scale genome sequencing studies.
Predicting drug safety and communicating risk: benefits of a Bayesian approach
Authors: Lazic Stanley E , Edmunds Nicholas , Pollard Christopher E.
Published: September 2017

Drug toxicity is a major source of attrition in drug discovery and development. Pharmaceutical companies routinely use preclinical data to predict clinical outcomes and continue to invest in new assays to improve predictions. However, there are many open questions about how to make the best use of available data, combine diverse data, quantify risk, and communicate risk and uncertainty to enable good decisions. The costs of suboptimal decisions are clear: resources are wasted and patients may be put at risk. We argue that Bayesian methods provide answers to all of these problems and use hERG-mediated QT prolongation as a case study. Benefits of Bayesian machine learning models include intuitive probabilistic statements of risk that incorporate all sources of uncertainty, the option to include diverse data and external information, and visualisations that have a clear link between the output from a statistical model and what this means for risk. Furthermore, Bayesian methods are easy to use with modern software, making their adoption for safety screening straightforward. We include R and Python code to encourage the adoption of these methods.
Isomorphous rare-earth bis[bis(2,6-diisopropylphenyl)phosphate] complexes and their self-assembly into two-dimensional frameworks by intramolecular hydrogen bonds
Authors: Minyaev Mikhail E. , Nifant'ev Ilya E. , Tavtorkin Alexander N. , Korchagina Sof'ya A. , Zeynalova Shadana Sh. , Ananyev Ivan V. , Churakov Andrei V.
Published: September 2017

The crystal structures of rare-earth diaryl- or dialkylphosphate derivatives are poorly explored. Crystals of bis[bis(2,6-diisopropylphenyl)phosphato-κO]chloridotetrakis(methanol-κO)neodymium methanol disolvate, [Nd(C24H34O4P)Cl(CH4O)4]·2CH3OH, (1), and of the lutetium, [Lu(C24H34O4P)Cl(CH4O)4]·2CH3OH, (2), and yttrium, [Y(C24H34O4P)Cl(CH4O)4]·2CH3OH, (3), analogues have been obtained by reactions between lithium bis(2,6-diisopropylphenyl)phosphate and LnCl3(H2O)6 (in a 2:1 ratio) in methanol. Compounds (1)–(3) crystallize in the C2/c space group. Their crystal structures are isomorphous. The molecule possesses C
2 symmetry with a twofold crystallographic axis passing through the Ln and Cl atoms. The bis(2,6-diisopropylphenyl)phosphate ligands all display a κ1
O-monodentate coordination mode. The coordination polyhedron for the metal atom [coordination number (CN) = 7] is a distorted pentagonal bipyramid. Each [Ln{O2P(O-2,6-iPr2C6H3)2}2Cl(CH3OH)4] molecular unit exhibits two intramolecular O—H...O hydrogen bonds, forming six-membered rings, and two intramolecular O—H...Cl interactions, forming four-membered rings. Intermolecular O—H...O hydrogen bonds connect each unit via four noncoordinating methanol molecules with four other units, forming a two-dimensional hydrogen-bond network. Crystals of bis[bis(2,6-diisopropylphenyl)phosphato-κO]tetrakis(methanol-κO)(nitrato-κ2
O,O′)neodymium methanol disolvate, [Nd(C24H34O4P)(NO3)(CH4O)4]·2CH3OH, (4), have been obtained in an analogous manner from NdCl3(H2O)6. Compound (4) also crystalizes in the C2/c space group. Its crystal structure is similar to those of (1)–(3). The κ2
O,O′-bidentate nitrate anion is disordered over a twofold axis, being located nearly on it. Half of the molecule is crystallographically unique (CNNd = 8). Unlike (1)–(3), complex (4) exhibits disorder of all three methanol molecules, one isopropyl group of the phosphate ligand and the NO3
− ligand. The structure of (4) displays intra- and intermolecular O—H...O hydrogen bonds similar to those in (1)–(3). Compounds (1)–(4) represent the first reported mononuclear bis[bis(diaryl/dialkyl)phosphate] rare-earth complexes.
Different supramolecular architectures mediated by different weak interactions in the crystals of three N-aryl-2,5-dimethoxybenzenesulfonamides
Authors: Shakuntala K. , Naveen S. , Lokanath N. K. , Suchetan P. A. , Abdoh M.
Published: September 2017

The synthesis and evaluation of the pharmacological activities of molecules containing the sulfonamide moiety have attracted interest as these compounds are important pharmacophores. The crystal structures of three closely related N-aryl-2,5-dimethoxybenzenesulfonamides, namely N-(2,3-dichlorophenyl)-2,5-dimethoxybenzenesulfonamide, C14H13Cl2NO4S, (I), N-(2,4-dichlorophenyl)-2,5-dimethoxybenzenesulfonamide, C14H13Cl2NO4S, (II), and N-(2,4-dimethylphenyl)-2,5-dimethoxybenzenesulfonamide, C16H19NO4S, (III), are described. The asymmetric unit of (I) consists of two symmetry-independent molecules, while those of (II) and (III) contain one molecule each. The molecular conformations are stabilized by different intramolecular interactions, viz. C—H...O interactions in (I), N—H...Cl and C—H...O interactions in (II), and C—H...O interactions in (III). The crystals of the three compounds display different supramolecular architectures built by various weak intermolecular interactions of the types C—H...O, C—H...Cl, C—H...π(aryl), π(aryl)–π(aryl) and Cl...Cl. A detailed Hirshfeld surface analysis of these compounds has also been conducted in order to understand the relationship between the crystal structures. The d
norm and shape-index surfaces of (I)–(III) support the presence of various intermolecular interactions in the three structures. Analysis of the fingerprint plots reveals that the greatest contribution to the Hirshfeld surfaces is from H...H contacts, followed by H...O/O...H contacts. In addition, comparisons are made with the structures of some related compounds. Putative N—H...O hydrogen bonds are observed in 29 of the 30 reported structures, wherein the N—H...O hydrogen bonds form either C(4) chain motifs or R
2
2(8) rings. Further comparison reveals that the characteristics of the N—H...O hydrogen-bond motifs, the presence of other interactions and the resultant supramolecular architecture is largely decided by the position of the substituents on the benzenesulfonyl ring, with the nature and position of the substituents on the aniline ring exerting little effect. On the other hand, the crystal structures of (I)–(III) display several weak interactions other than the common N—H...O hydrogen bonds, resulting in supramolecular architectures varying from one- to three-dimensional depending on the nature and position of the substituents on the aniline ring.
Crystal structure of a new polymorph of di(thiophen-3-yl) ketone
Authors: Hübscher Jörg , Augustin André U. , Seichter Wilhelm , Weber Edwin
Published: September 2017

The crystal structure of the title compound, C9H6OS2, represents a new polymorph. The crystal structure was solved in the orthorhombic space groupPbcnwith one half of the molecule in the asymmetric unit. The thiophene rings are perfectly planar and twisted with respect to each other, showing the molecule to be in an S,O-trans/S,O-transconformation. In the crystal, C—H...O hydrogen bonds connect the molecules into layers extending parallel to theabplane. The crystal structure also features π–π interactions.
Residents’ perceptions of the impact of tourism in Abu Dhabi, United Arab Emirates
Authors: Hammad Nada , Ahmad Syed Zamberi , Papastathopoulos Avraam
Published: September 2017

Purpose

This paper aims to investigate residents’ perceptions of tourism’s impact on their support for tourism development in Abu Dhabi, United Arab Emirates (UAE).

Design/methodology/approach

Data were collected using self-administered questionnaires from Abu Dhabi residents (n= 407), who represented 30 nationalities residing in the emirate. Based on social exchange theory, structural equation modeling was used to test hypotheses.

Findings

Results suggest that Abu Dhabi residents perceive the impacts of tourism positively and are more sensitive to the environmental and economic influences of tourism than the social and cultural influences.

Research limitations/implications

This study was limited to Abu Dhabi residents; findings cannot be generalized to other emirates in the UAE, or other countries.

Originality/value

This study adds value to extant tourism literature by investigating residents’ perceptions of the influence of tourism in one of the richest cities worldwide, which aspires to be one of the fastest growing tourism destinations in the Middle East.
Vacation happiness bias
Authors: Chang Seohee
Published: September 2017

Purpose

The purpose of this paper is to theoretically formulate the plausibility of affective recalling through the analysis of different psychological theories and assumptions and develops the theory of vacation happiness bias on the emergence of some variations on affective recalling and forecasting intertwined with dispositional affect, affect regulation and types of situational affect.

Design/methodology/approach

This study uses a non-empirical method to find gaps in the literature and the existing theories and build a new theoretical model, vacation happiness bias.

Findings

The theory of vacation happiness bias accounts for how the modified focalism model that is expanded to affective recalling beyond affective forecasting works, and thus the modified model is better accounted particularly for the vacation field. In addition, the theory of vacation happiness bias explains how different types of affect and affect regulation are intertwined with one another within the modified focalism frame, thereby yielding some variation. Recalled vacation experiences are more positive than vacation experiences as of the present as a result of affect that is controlled through affect regulation merged with social desirability bias.

Originality/value

Research in tourism and psychology fields has not yet deemed affective recalling, even though affective recalling would likely be more salient in the vacation context that is different from the context of daily life.
Earnings management in interconnected networks: a perspective
Authors: Ozili Peterson K.
Published: September 2017

Purpose

The purpose of this paper is to examine how firms manage earnings when firms are in interconnected networks, that is, when firms are interconnected to each other in a way that the survival of one firm is crucial to the survival of other firms connected to it.

Design/methodology/approach

The paper employs network typology to provide some insight on the earnings management behaviour of firms in regulated and unregulated networks or systems.

Findings

The author shows that firms in the inner core of interconnected networks are more likely to rely on income-smoothing behaviour as a preferred form of earnings management because it stabilises the firm’s link with other firms in the network. In regulated networks, the author proposes a negative relationship between a firm’s network centrality and the number of earnings management strategies the manager can adopt. Also, the author proposes a positive relationship between a firm’s network centrality and the propensity to smooth earnings or income when firms are concerned about their reputation or regulatory scrutiny.

Originality/value

This paper is a brief note on earnings management, and is the first study to provide a perspective on how earnings management can be explained using a network typology.
Don't be so emotional! How tone of voice and service type affect the relationship between message valence and consumer responses to WOM in social media
Authors: De Keyzer Freya , Dens Nathalie , De Pelsmacker Patrick
Published: September 2017

Purpose

The purpose of this paper is to shed light on the boundary conditions of the effect of the valence of word-of-mouth on social networking sites (sWOM) on consumer responses (attitude toward the service provider, purchase intention and positive word-of-mouth intention). Specifically, the authors examine two moderators: the tone of voice (factual vs emotional) of the sWOM and service type (utilitarian vs hedonic) of the service that the sWOM is about.

Design/methodology/approach

A 2 (message valence: positive vs negative) × 2 (tone of voice: factual vs emotional) × 2 (service type: utilitarian vs hedonic) full-factorial between-subjects online experiment with 400 respondents was conducted and the data were analyzed using Hayes’ PROCESS macro.

Findings

The results show that message valence exerts a greater impact on consumer responses with factual sWOM messages compared to emotional ones. Furthermore, the impact of message valence is stronger for hedonic services compared to utilitarian services. In contrast to the authors’ expectations, there is no significant impact of matching the tone of voice to the service type.

Practical implications

First, for sWOM senders, factual messages are found to be more influential: backing an sWOM up with arguments and specific details increases the chance of it affecting consumers’ responses. As a result, marketers, especially of predominantly hedonic services, should encourage their followers and customers to spread positive factual sWOM about their service.

Originality/value

The study tests two previously unstudied moderating variables that affect the relationship between message valence and consumer responses to sWOM messages. Moreover, this study provides interesting insights for marketers and bloggers or reviewers.
miR‐181d‐5p promotes neurite outgrowth in PC12 Cells via PI3K/Akt pathway
Authors: Shen Li‐Ming , Song Zhi‐Wen , Hua Yin , Chao Xu , Liu Jin‐Bo
Published: September 2017

Introduction

miRNAs dysregulate in spinal cord injury (SCI) and have been demonstrated to play a crucial role in neurite outgrowth. However, the underlying mechanism remains elusive. In this study, we constructed a mouse model of SCI, extracted RNA from injured spinal cord tissue for the use of microarray assay. miR‐181d‐5p which is one of the most significantly expressed miRNAs in miRNA‐mRNA network, abundantly expressed in center system and highly conserved across different spices, was chosen for our further study.

Aims

To demonstrate whether miR‐181d‐5p can promote neurite outgrowth in PC12 cells via PI3K/Akt signaling pathway, we performed function analysis of miR‐181d‐5p with LV‐miR‐181d‐5p and LV‐sh‐GFP to infect PC12 cells.

Results

Through microarray assay analysis, we totally found 262 significantly expressed miRNAs and 2973 target genes in SCI and observed that their expression dynamically changed postinjury. Here, we provided enough evidences that the overexpression of miR181d‐5p significantly decreased the expression of PTEN, upregulated p‐Akt expression, increased neurite outgrowth‐related proteins (GAP‐43 and NF‐200) and synaptic vesicle‐related proteins (Synapsin and PSD95), and then promoted neurite outgrowth in PC12 cells. Furthermore, we confirmed that miR‐181d‐5p could directly target to the 3′‐UTR of PTEN mRNA through dual‐luciferase report assay.

Conclusions

Our study supports that aberrant expression of miRNAs is involved in the pathogenesis of SCI, miR‐181d‐5p plays an important role in neurite growth in PC12 cells via PI3K/Akt signaling pathway and may be a candidate target for the treatment of SCI in the future.
Differences in right ventricular morphology, not function, indicate the nature of increased afterload in pulmonary hypertensive subjects with normal left ventricular function
Authors: Raza Farhan , Dillane Catherine , Mirza Arslan , Brailovsky Yevgeniy , Weaver Sheila , Keane Martin G. , Forfia Paul
Published: September 2017

Background

The aim of study was to assess whether a specific morphology of the right ventricle (RV) by 2D echo predicts the hemodynamic nature of pulmonary hypertension (PH).

Methods

We reviewed clinical, 2D echo, and hemodynamic data of 100 patients with PH: divided into three groups: PH from pulmonary vascular disease (PHPVD; n = 34) with pulmonary vascular resistance (PVR) > 3 mm Hg/L/min (Wood unit [WU]) and pulmonary artery wedge pressure (PAWP) ≤ 15 mm Hg, pulmonary venous hypertension (PVH; n = 33) with PVR < 3 WU and PAWP > 15 mm Hg and PHMIXED (n = 33) with PVR > 3 WU and PAWP > 15 mm Hg. We analyzed several two‐dimensional parameters of right heart morphology and function, including the degree of tapering of the RV diameter from base (just above tricuspid annulus) to apex (level of moderator band) in the apical four‐chamber view. P = <.05.

Results

Baseline characteristics were similar in all three groups: age 62 ± 14.4 years, 69% females, 57% Caucasians. Hemodynamics and 2D echo data of PHPVD vs PVH vs PHMIXED were as follows: PVR 13 ± 6 vs 2 ± 1 vs 7 ± 2 WU, mean pulmonary artery pressure 53 ± 14 vs 34 ± 8 vs 49 ± 8 mm Hg and cardiac index 2.0 ± 0.5 vs 2.8 ± 0.7 vs 2.2 ± 0.7 L/m2, RV base/apex ratio during systole (sRVb/a) 1.3 ± 0.2 vs 2.6 ± 0.5 vs 1.5 ± 0.3. Thus, sRVb/a was twofold higher in the PVH vs PHPVD cohort. On ROC analysis, the AUC for sRVb/a for predicting PVR > 3 WU was 0.873, with optimal cutoff of 1.5.

Conclusion

Systolic RV base/apex ratio is a simple 2D index of RV shape that powerfully predicts a PVR > 3 WU and provides powerful discriminating ability between PVH and PHPVD.