Τρίτη 27 Νοεμβρίου 2018

OCMA: Fast, Memory-Efficient Factorization of Prohibitively Large Relationship Matrices

Matrices representing genetic relatedness among individuals (i.e., Genomic Relationship Matrices, GRMs) play a central role in genetic analysis. The eigen-decomposition of GRMs (or its alternative that generates fewer top singular values using genotype matrices) is a necessary step for many analyses including estimation of SNP-heritability, Principal Component Analysis (PCA), and genomic prediction. However, the GRMs and genotype matrices provided by modern biobanks are too large to be stored in active memory. To accommodate the current and future "bigger-data", we develop a disk-based tool, Out-of-Core Matrices Analyzer (OCMA), using state-of-the-art computational techniques that can nimbly perform eigen and Singular Value Decomposition (SVD) analyses. By integrating memory mapping (mmap) and the latest matrix factorization libraries, our tool is fast and memory-efficient. To demonstrate the impressive performance of OCMA, we test it on a personal computer. For full eigen-decomposition, it solves an ordinary GRM (N=10,000) in 55 seconds. For SVD, a commonly used faster alternative of full eigen-decomposition in genomic analyses, OCMA solves the top 200 singular values (SVs) in half an hour, top 2,000 SVs in 0.95 hour, and all 5,000 SVs in 1.77 hours based on a very large genotype matrix (N=1,000,000, M=5,000) on the same personal computer. OCMA also supports multi-threading when running in a desktop or HPC cluster. Our OCMA tool can thus alleviate the computing bottleneck of classical analyses on large genomic matrices, and make it possible to scale up current and emerging analytical methods to big genomics data using lightweight computing resources.



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Dosage Compensation and Gene Expression of the X Chromosome in Sheep

Ohno's hypothesis predicts that the expression of the single X chromosome in males needs compensatory upregulation to balance its dosage with that of the diploid autosomes. Additionally, X chromosome inactivation ensures that quadruple expression of the two X chromosomes is avoided in females. These mechanisms have been actively studied in mice and humans but lag behind in domestic species. Using RNA sequencing data, we analyzed the X chromosome upregulation in sheep fetal tissues from day 135 of gestation under control, over or restricted maternal diets (100%, 140% and 60% of National Research Council Total Digestible Nutrients), and in conceptuses, juvenile, and adult somatic tissues. By computing the mean expression ratio of all X-linked genes to all autosomal genes (X:A), we found that all samples displayed some levels of X chromosome upregulation. The degrees of X upregulation were not significant (P-value = 0.74) between ovine females and males in the same somatic tissues. Brain, however, displayed complete X upregulation. Interestingly, the male and female reproduction-related tissues exhibited divergent X dosage upregulation. Moreover, expression upregulation of the X chromosome in fetal tissues was not affected by maternal diets. Maternal nutrition, however, did change expression levels of several X-linked genes, such as sex determination genes SOX3 and NR0B1. In summary, our results showed that X chromosome upregulation occurred in nearly all sheep somatic tissues analyzed, thus support Ohno's hypothesis in a new species. However, the levels of upregulation differed by different subgroups of genes such as those that are house-keeping and "dosage-sensitive".



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Medaka Population Genome Structure and Demographic History Described via Genotyping-by-Sequencing

Medaka is a model organism in medicine, genetics, developmental biology and population genetics. Lab stocks composed of more than 100 local wild populations are available for research in these fields. Thus, medaka represents a potentially excellent bioresource for screening disease-risk- and adaptation-related genes in genome-wide association studies. Although the genetic population structure should be known before performing such an analysis, a comprehensive study on the genome-wide diversity of wild medaka populations has not been performed. Here, we performed genotyping-by-sequencing (GBS) for 81 and 12 medakas captured from a bioresource and the wild, respectively. Based on the GBS data, we evaluated the genetic population structure and estimated the demographic parameters using an approximate Bayesian computation (ABC) framework. The genome-wide data confirmed that there were substantial differences between local populations and supported our previously proposed hypothesis on medaka dispersal based on mitochondrial genome (mtDNA) data. A new finding was that a local group that was thought to be a hybrid between the northern and the southern Japanese groups was actually an origin of the northern Japanese group. Thus, this paper presents the first population-genomic study of medaka and reveals its population structure and history based on chromosomal genetic diversity.



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High Efficiency Targeting of Non-coding Sequences Using CRISPR/Cas9 System in Tilapia

The CRISPR/Cas9 has been successfully applied for disruption of protein coding sequences in a variety of organisms. The majority of the animal genome is actually non-coding sequences, which are key regulators associated with various biological process. In this study, to understand the biological signifi­cance of these sequences, we used one or dual gRNA guided Cas9 nuclease to achieve specific deletion of non-coding sequences including microRNA and 3' untranslated region (UTR) in tilapia, which is an important fish for studying sex determination and evolution. Co-injection of fertilized eggs with single gRNA targeting seed region of miRNA and Cas9 mRNA resulted in indel mutations. Further, co-injection of fertilized eggs with dual gRNAs and Cas9 mRNA led to the removal of the fragment between the two target loci, yielding maximum efficiency of 11%. This highest genomic deletion efficiency was further improved up to 19% using short ssDNA as a donor. The deletions can be transmitted through the germline to the next generation at average efficiency of 8.7%. Cas9-vasa 3'-UTR was used to increase the efficiency of germline transmission of non-coding sequence deletion up to 14.9%. In addition, the 3'-UTR of the vasa gene was successfully deleted by dual gRNAs. Deletion of vasa 3'-UTR resulted in low expression level of vasa mRNA in the gonad when compared with the control. To summarize, the improved CRISPR/Cas9 system provided a powerful platform that can assist to easily generate desirable non-coding sequences mutants in non-model fish tilapia to discovery their functions.



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Simulation Training Improves Resuscitation Team Leadership Skills of Nurse Practitioners

In the current era of limited physician trainee work hours, limited nurse practitioner orientation times, and highly specialized care settings, frontline providers have limited opportunities for mentored resuscitation training in emergency situations. We aimed to evaluate the effectiveness of a pilot program to improve resuscitation team leadership skills of nurse practitioners using simulation-based training.

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Perceptions of Gastrostomy Buttons Among Caregivers of Children With Special Health Care Needs

Children with special health care needs (CSHCN) have chronic conditions that generally are classified as developmental disabilities. Children with developmental disabilities are at high risk of malnutrition. Gastrostomy buttons are frequently used to provide enteral nutrition for children with developmental disabilities.

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The Evaluation and Treatment of Tall Stature in Preadolescent Girls: A Case Report

Families may approach primary care providers for advice and treatment for tall stature (height more than two standard deviations above the mean height for a given age) in pre-pubertal children. The following case report describes an 11-year-old girl who was referred to an endocrinology specialist for familial tall stature. Potential pathological causes for tall stature are reviewed. The assessment, management, and risks and benefits of treatment for this condition are described. Finally, the role of the pediatric nurse practitioner in caring for youth with this chief complaint is discussed.

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Comparison of Pyogenic Postoperative and Native Vertebral Osteomyelitis

Postoperative vertebral osteomyelitis (PVO) after spinal surgery is a clinical challenge. However, there is a paucity of evidence regarding the most likely etiologic organisms to guide the choice of empirical antibiotic therapy, and previous reports of treatment outcomes for PVO are scarce.

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A web-based platform to accommodate symptoms of anxiety and depression by featuring social interaction and animated information in patients undergoing lumbar spine fusion: a randomized clinical trial

Approximately one-third of patients undergoing spine surgery have symptoms of anxiety and depression that correlate with pain, disability, and lower health-related quality of life. The use of web-based informative strategies before surgery and principles from cognitive behavioral therapy, have been applied in other patient groups, facilitating mobility and encouraging beneficial coping behavior.

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Staphylococcus aureus Infecting and Colonizing Experimental Animals, Macaques, in a Research Animal Facility

Microbial Drug Resistance, Ahead of Print.


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Messages from the auricle ‐ limiting progression of heart failure with preserved ejection fraction through transcutaneous nerve stimulation of nerves in the external ear



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Global impacts of chromosomal imbalance on gene expression in Arabidopsis and other taxa [Genetics]

Changes in dosage of part of the genome (aneuploidy) have long been known to produce much more severe phenotypic consequences than changes in the number of whole genomes (ploidy). To examine the basis of these differences, global gene expression in mature leaf tissue for all five trisomies and in diploids,...

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Associations between Symptoms of Temporomandibular Disorders, Quality of Life and Psychological States in Asian Military Personnel

Abstract

Background

Symptoms of Temporomandibular Disorders (TMD) could affect oral‐health related quality of life (OHRQoL) and psychological distress.

Objective

This study aims to determine the prevalence of TMD symptoms, and impact of type and number of TMD symptoms on OHRQoL and psychological states among Asian military personnel.

Method

The study was conducted across 12 military dental centres using self‐administered questionnaire comprising demographical data, DC/TMD symptom questionnaire, OHIP‐14 and DASS‐21. 3028 personnel, aged between 18‐65 years old, were invited to participate with an acceptance rate of 90.5%. Data analysis was done using non‐parametric tests, regression analysis and Spearman correlation (p< 0.05

Results

Out of 2043 subjects (1998 males; 45 females, mean age 24.18±7.18 years), 36.32% (n=742) reported at least one TMD symptom. Significant differences in summary OHIP‐14, depression, anxiety and stress scores were observed between subjects with and without TMD symptoms. Significant differences in OHIP‐14 and DASS‐21 scores were observed between dissimilar type and number of TMD symptoms in the TMD group. Those with headaches and 2‐3 symptoms have substantially poorer OHRQoL and greater psychological distress. Associations between number of TMD symptoms, quality of life, depression, anxiety and stress were significant but weak (r=0.19‐0.40).

Conclusions

TMD symptoms were prevalent among Asian military population. Significant differences in OHRQoL and psychological states were observed between subjects with and without TMD symptoms. Specific type and number of TMD symptoms impacted OHRQoL and psychological states differently. Associations between number of TMD symptoms and quality of life, depression, anxiety and stress were significant but weak.

This article is protected by copyright. All rights reserved.



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A novel ISLR2 -linked autosomal recessive syndrome of congenital hydrocephalus, arthrogryposis and abdominal distension

Abstract

ISLR2 (immunoglobulin superfamily containing leucine-rich repeat 2), encodes a protein involved in axon guidance in brain development (hence the other name leucine-rich repeat domain- and immunoglobulin domain-containing axon extension proteins; LINX). A recently described mouse knockout displays hydrocephalus. However, the corresponding phenotype in humans is unknown. Here, we describe a multiplex consanguineous family in which a homozygous truncating variant in ISLR2 segregates with severe congenital hydrocephalus, arthrogryposis multiplex congenita and abdominal distension. We suggest this syndrome may represent the human "knockout" phenotype for ISLR2.



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Clinical epigenetics: seizing opportunities for translation

Clinical epigenetics: seizing opportunities for translation

Clinical epigenetics: seizing opportunities for translation, Published online: 27 November 2018; doi:10.1038/s41576-018-0074-2

Disruptions to the epigenome occur during the pathogenesis of various human diseases. In this Review, Berdasco and Esteller describe the challenges and progress of harnessing epigenetic changes for clinical application, including for diagnostics, disease classification and therapeutics. They discuss applications to diverse diseases, such as cancer, neurological disease, immune disorders and viral infections.

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New fossils, systematics, and biogeography of the oldest known crown primate Teilhardina from the earliest Eocene of Asia, Europe, and North America

Publication date: Available online 27 November 2018

Source: Journal of Human Evolution

Author(s): Paul E. Morse, Stephen G.B. Chester, Doug M. Boyer, Thierry Smith, Richard Smith, Paul Gigase, Jonathan I. Bloch

Abstract

Omomyiform primates are among the most basal fossil haplorhines, with the oldest classified in the genus Teilhardina and known contemporaneously from Asia, Europe, and North America during the Paleocene–Eocene Thermal Maximum (PETM) ∼56 mya. Characterization of morphology in this genus has been limited by small sample sizes and fragmentary fossils. A new dental sample (n = 163) of the North American species Teilhardina brandti from PETM strata of the Bighorn Basin, Wyoming, documents previously unknown morphology and variation, prompting the need for a systematic revision of the genus. The P4 of T. brandti expresses a range of variation that encompasses that of the recently named, slightly younger North American species 'Teilhardina gingerichi,' which is here synonymized with T. brandti. A new partial dentary preserving the alveoli for P1-2 demonstrates that T. brandti variably expresses an unreduced, centrally-located P1, and in this regard is similar to that of T. asiatica from China. This observation, coupled with further documentation of variability in P1 alveolar size, position, and presence in the European type species T. belgica, indicates that the original diagnosis of T. asiatica is insufficient at distinguishing this species from either T. belgica or T. brandti. Likewise, the basal omomyiform 'Archicebus achilles' requires revision to be distinguished from Teilhardina. Results from a phylogenetic analysis of 1890 characters scored for omomyiforms, adapiforms, and other euarchontan mammals produces a novel clade including T. magnoliana, T. brandti, T. asiatica, and T. belgica to the exclusion of two species previously referred to Teilhardina, which are here classified in a new genus (Bownomomys americanus and Bownomomys crassidens). While hypotheses of relationships and inferred biogeographic patterns among species of Teilhardina could change with the discovery of more complete fossils, the results of these analyses indicate a similar probability that the genus originated in either Asia or North America.



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An overview of rice genetics research in China

Publication date: 20 November 2018

Source: Journal of Genetics and Genomics, Volume 45, Issue 11

Author(s): James A. Birchler



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Highlights of genetics research over the past four decades in China

Publication date: 20 November 2018

Source: Journal of Genetics and Genomics, Volume 45, Issue 11

Author(s): Yongbiao Xue, Yaping Zhang



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Clinical epigenetics: seizing opportunities for translation



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Association between cigarette smoking and alcohol consumption and sessile serrated polyps in subjects 30 to 49 years old

Clinical Gastroenterology and Hepatology

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Determinants of sporadic Campylobacter infections in Denmark: A nationwide case-control study among children and young adults

Clinical Epidemiology

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Gender Disparities in Trauma Care: How Sex Determines Treatment, Behavior, and Outcome

Publication date: Available online 27 November 2018

Source: Anesthesiology Clinics

Author(s): Evie G. Marcolini, Jennifer S. Albrecht, Kinjal N. Sethuraman, Lena M. Napolitano



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A Systematic Review and Narrative Synthesis on the histological and neurobehavioral long term effects of dexmedetomidine

Abstract

Background

Recent experimental studies suggest that currently used anesthetics have neurotoxic effects on young animals. Clinical studies are increasingly published about the effects of anesthesia on the long term outcome, providing contradictory results. The selective alpha‐2 adrenergic receptor agonist dexmedetomidine has been suggested as an alternative non‐toxic sedative agent.

Aim

The aim of this systematic review is to assess the potential neuroprotective and neurobehavioral effects of dexmedetomidine in young animals and children.

Methods

Systematic searches separately for preclinical and clinical studies were performed in Medline Ovid and Embase on February 14th 2018.

Results

The initial search found preclinical (n=661) and clinical (n=240) studies. A total of 20 preclinical studies were included. None of the clinical studies met the predefined eligibility criteria.

Histologic injury by dexmedetomidine was evaluated in 11 studies, and was confirmed in three of these studies (caspase‐3 activation or apoptosis). Decrease of injury caused by another anesthetic was evaluated in 16 studies and confirmed in 13 of these.

Neurobehavioral tests were performed in 7 out of the 20 studies. Of these 7 rodent studies, 3 studies tested the effects of dexmedetomidine alone on neurobehavioral outcome in animals (younger than P21). All 3 studies found no negative effect of dexmedetomidine on the outcome. In 6 studies outcome was evaluated when dexmedetomidine was administered following another anesthetic. Dexmedetomidine was found to lessen the negative effects of the anesthetic.

Conclusion

In animals, dexmedetomidine was found not to induce histologic injury and to show a beneficial effect when administered with another anesthetic. No clinical results on the long term effects in children have been identified yet.

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