Muscular System Development Research Articles

Transcriptome analysis reveals the effects of Schizochytrium sp. on the meat quality attributes of Tan lambs

Schizochytrium sp., a feed additive, positively affects the quality of animal meat. In this study, the molecular mechanisms through which dietary Schizochytrium sp. affects the meat quality characteristics of Tan lambs were investigated using transcriptomic techniques. The findings demonstrate that the lambs supplemented with Schizochytrium sp. had a larger loin eye area and a higher average daily gain and intramuscular fat content (P < 0.05). They also had lower drip loss (at 24 and 48 h) and shear force (P < 0.05). Further, 745 genes were differentially expressed between lambs supplemented with Schizochytrium and the control group. Moreover, KEGG pathway analysis showed that the ECM-receptor interaction pathway, which is related to muscle generation and intramuscular fat deposition, was significantly enriched in the lambs administered a diet containing Schizochytrium sp. Herein, we identified some pivotal genes linked to muscular system development and lipid metabolism. Thus, using Schizochytrium sp. may boost the meat quality of Tan lambs by modifying the expression of genes related to hub pathways. The results supply a new basis to determine the molecular mechanisms through which Schizochytrium sp. supplementation regulates the meat quality characteristics of sheep.

Effects of Dietary Vitamin E on Intramuscular Fat Deposition and Transcriptome Profile of the Pectoral Muscle of Broilers.

Vitamin E is an essential micronutrient for animals. The aim of this study was to determine the effect of vitamin E on intramuscular fat (IMF) deposition and the transcriptome profile of the pectoral muscle in broiler chickens. Arbor Acres chickens were divided into five treatment groups fed a basal diet supplemented with 0, 20, 50, 75, and 100 IU/kg dietary DL-α-tocopheryl acetate (vitamin E), respectively. Body weight, carcass performance, and IMF content were recorded. Transcriptome profiles of the pectoral muscles of 35-day-old chickens in the control and treatment groups (100 IU/kg of vitamin E) were obtained by RNA sequencing. The results showed that diets supplemented with 100 IU/kg of vitamin E significantly increased IMF deposition in chickens on day 35. In total, 159 differentially expressed genes (DEGs), including 57 up-regulated and 102 down-regulated genes, were identified in the treatment (100 IU/kg vitamin E) group compared to the control group. These DEGs were significantly enriched in 13 Gene Ontology terms involved in muscle development and lipid metabolism; three signaling pathways, including the mitogen-activated protein kinase and FoxO signaling pathways, which play key roles in muscular and lipid metabolism; 28 biofunctional categories associated with skeletal and muscular system development; 17 lipid metabolism functional categories; and three lipid metabolism and muscle development-related networks. The DEGs, pathways, functional categories, and networks identified in this study provide new insights into the regulatory roles of vitamin E on IMF deposition in broilers. Therefore, diets supplemented with 100 IU/kg of vitamin E will be more beneficial to broiler production.

RESULTS OF EXPERIMENTAL VERIFICATION OF THE REALIZATION OF PEDAGOGICAL TECHNOLOGY OF PE TEACHERS’ SELF-IMPROVEMENT IN THE PROCESS OF PROFESSIONAL ACTIVITY AT VARIOUS STAGES OF PROFESSIONAL DEVELOPMENT

The article deals with the issue of professional development and peculiarities of self-improvement of teachers of physical education. The aim of the research is to define components of self-improvement of teachers of physical education at various stages of professional development, and to theoretically substantiate and experimentally check realization of pedagogical technology of teachers’ self-improvement in the process of professional activity. Teachers of physical education from higher educational establishments took part in the experiment. A number of methods were used: analysis, comparison, systematization, survey, discussion, teachers interviewing, questionnaire, pedagogical experiment, methods of mathematical statistics, and graphic display of results. Results of the stating experiment proved discrepancy of the actual state of components of PE teachers’ self-improvement in the process of activity of professional perfection guideline. &#x0D; In order to define physical state of PE teachers, tests aimed at physical preparedness have been selected; physiological indices have been defined with the help of functional tests; to characterize muscle component of PE teachers, muscular system development index has been used. For a good evaluation of indices of physical preparedness, physiological, and morphological indices, 9-grade evaluation charts have been developed. Analysis of the level of theoretical and methodological preparedness, pedagogical communication, and computer literacy of PE teachers was done with questionnaires developed by us. Definition of motivation to self-improvement of teachers of physical education in the process of professional activity was done on the basis of the “Motivation Sources Inventory” (J. Barbuto, R. Scholl).&#x0D; Also, results of practical experience allowed to elaborate the structure of self-improvement of teacher of physical education, which includes the following components: theoretical and methodological knowledge, pedagogical communication, physical self-improvement, computer literacy and personal view on self-improvement of teachers of physical education in the process of professional activity, which we define as an individual process of improvement of professionally-significant components of activity oriented on “Professional I-ideal”. “Professional I-ideal” is construed by us as a concept of professional qualities and features that a teacher must possess being oriented on professional requirements.

Long-term changes in plasma proteomic profiles in premenopausal and postmenopausal Black and White women: the Atherosclerosis Risk in Communities study.

The activity, localization, and turnover of proteins within cells and plasma may contribute to physiologic changes during menopause and may influence disease occurrence. We examined cross-sectional differences and long-term changes in plasma proteins between premenopausal and naturally postmenopausal women. We used data from 4,508 (19% Black) women enrolled in the Atherosclerosis Risk in Communities study. SOMAscan multiplexed aptamer technology was used to measure 4,697 plasma proteins. Linear regression models were used to compare differences in proteins at baseline (1993-1995) and 18-year change in proteins from baseline to 2011-2013. At baseline, 472 women reported being premenopausal and 4,036 women reported being postmenopausal, with average ages of 52.3 and 61.4 years, respectively. A greater proportion of postmenopausal women had diabetes (15 vs 9%), used hypertension (38 vs 27%) and lipid-lowering medications (10 vs 3%), and had elevated total cholesterol and waist girth. In multivariable adjusted models, 38 proteins differed significantly between premenopausal and postmenopausal women at baseline, with 29 of the proteins also showing significantly different changes between groups over the 18-year follow-up as the premenopausal women also reached menopause. These proteins were associated with various molecular/cellular functions (cellular development, growth, proliferation and maintenance), physiological system development (skeletal and muscular system development, and cardiovascular system development and function), and diseases/disorders (hematological and metabolic diseases and developmental disorders). We observed significantly different changes between premenopausal and postmenopausal women in several plasma proteins that reflect many biological processes. These processes may help to understand disease development during the postmenopausal period.

Octopamine signaling via OctαR is essential for a well-orchestrated climbing performance of adult Drosophila melanogaster

The biogenic amine octopamine (OA) orchestrates many behavioural processes in insects. OA mediates its function by binding to OA receptors belonging to the G protein-coupled receptors superfamily. Despite the potential relevance of OA, our knowledge about the role of each octopaminergic receptor and how signalling through these receptors controls locomotion still limited. In this study, RNA interference (RNAi) was used to knockdown each OA receptor type in almost all Drosophila melanogaster tissues using a tubP-GAL4 driver to investigate the loss of which receptor affects the climbing ability of adult flies. The results demonstrated that although all octopaminergic receptors are involved in normal negative geotaxis but OctαR-deficient flies had impaired climbing ability more than those deficient in other OA receptors. Mutation in OA receptors coding genes develop weak climbing behaviour. Directing knockdown of octαR either in muscular system or nervous system or when more specifically restricted to motor and gravity sensing neurons result in similar impaired climbing phenotype, indicating that within Drosophila legs, OA through OctαR orchestrated the nervous system control and muscular tissue responses. OctαR-deficient adult males showed morphometric changes in the length and width of leg parts. Leg parts morphometric changes were also observed in Drosophila mutant in OctαR. Transmission electron microscopy revealed that the leg muscles OctαR-deficient flies have severe ultrastructural changes compared to those of control flies indicating the role played by OctαR signalling in normal muscular system development. The severe impairment in the climbing performance of OctαR-deficient flies correlates well with the completely distorted leg muscle ultrastructure in these flies. Taken together, we could conclude that OA via OctαR plays an important multifactorial role in controlling locomotor activity of Drosophila.

Integrative analysis of transcriptomics and proteomics of longissimus thoracis of the Hu sheep compared with the Dorper sheep

Meat quality is becoming more important for sheep breeding programs. Meat quality is a complex trait affected by genetic and environmental factors. In the present study, an integrative analysis of the longissimus thoracis tissue transcriptome and proteome was conducted to identify genes, proteins, and pathways related to meat quality in sheep. The sheep breeds Hu and Dorper were considered. These breeds were compared for the differences in muscle fiber structure, chemical composition, and amino acid composition. In the Hu sheep vs. Dorper sheep comparison, 22 DEGs/DEPs showed the same mRNA and protein expression trends. These genes are associated with lipid transport, lipid metabolism, and muscular system development. Moreover, some pathways such as “lipid transport”, “lipoprotein metabolic process”, “Alanine, aspartate and glutamate metabolism”, and “Arginine biosynthesis” were significantly enriched in this study. The reliability of the RNA-Seq results was verified by qRT-PCR. These findings provide new insights into the molecular mechanisms of meat quality in sheep.

Використання дихальної гімнастики для дітей, які заїкаються.

The overcoming stuttering peculiarities from the integrated approach standpoint, where one of the means is breathing gymnastics, are highlighted in the article. Breathing gymnastics that provide correct speech breathing, exercises acquiring the correct full inhalation and exhalation skills, fixed exhalation with sound, emphasis on the breathing simulation gymnastics use for children with stuttering, breathing gymnastics with elements of phonation gymnastics and playful breathing are described. Emphasis is placed on physical exercises that promote the muscular system development and the coordinated movements education, improving lung function, heart rate, metabolism, create a good mood in children and stimulate them to certain activities. Corrective work has been carried out to improve respiratory gymnastics in children who stutter, it was found that breathing exercises, as an important component of a comprehensive system to overcome stuttering, aimed at maintaining and improving children's health, improving physical fitness and efficiency, which promotes the formation and normalization of speech, the development of positive personal qualities in children of this category. It is noted that mastering the complex of respiratory gymnastics should be done gradually. It is emphasized that performing breathing exercises with forcing stuttering children can lead to unpleasant subjective feelings. It is investigated that respiratory gymnastic exercises should be used in all periods of corrective action

Prenatal Bisphenol a Exposure, DNA Methylation, and Low Birth Weight: A Pilot Study in Taiwan.

Prenatal exposure to bisphenol A (BPA) may increase the risk of abnormal birth outcomes, and DNA methylation might mediate these adverse effects. This study aimed to investigate the effects of maternal BPA exposure on maternal and fetal DNA methylation levels and explore whether epigenetic changes are related to the associations between BPA and low birth weight. We collected urine and blood samples originating from 162 mother-infant pairs in a Taiwanese cohort study. We measured DNA methylation using the Illumina Infinium HumanMethylation 450 BeadChip in 34 maternal blood samples with high and low BPA levels based on the 75th percentile level (9.5 μg/g creatinine). Eighty-seven CpGs with the most differentially methylated probes possibly interacting with BPA exposure or birth weight were selected using two multiple regression models. Ingenuity pathway analysis (IPA) was utilized to narrow down 18 candidate CpGs related to disease categories, including developmental disorders, skeletal and muscular disorders, skeletal and muscular system development, metabolic diseases, and lipid metabolism. We then validated these genes by pyrosequencing, and 8 CpGs met the primer design score requirements in 82 cord blood samples. The associations among low birth weight, BPA exposure, and DNA methylation were analyzed. Exposure to BPA was associated with low birth weight. Analysis of the epigenome-wide findings did not show significant associations between BPA and DNA methylation in cord blood of the 8 CpGs. However, the adjusted odds ratio for the dehydrogenase/reductase member 9 (DHRS9) gene, at the 2nd CG site, in the hypermethylated group was significantly associated with low birth weight. These results support a role of BPA, and possibly DHRS9 methylation, in fetal growth. However, additional studies with larger sample sizes are warranted.

Intensity of muscular system growth in purebred and crossbred steers depending on functional loads

The intensity of muscular system growth is largely determined by functional loads on it, and the frequency of growth and development of muscular system is associated with successive differentiations and is largely due to age-related changes in the level of sex steroids. Since crossbreeding is one of the effective methods of expanding the slaughter contingent of cattle the study of the intensity of muscular system growth of carcasses in purebred and crossbred animals is relevant and has indisputable practical application. The results of researches devoted to the study of the influence of functional loads on the intensity of growth and development of muscular system in steers of Blackand-White breed and its hybrids with Aberdeen-Angus and Charolais have been presented in the article. Muscle mass of carcasses was the biggest in Charolais crossbreds at the age of 12, 15 and 18 months it was, respectively, 172,4; 213,8 and 253,6 kg, which is significantly more than in herdmates of the maternal breed and Aberdeen-Angus crossbreds. The periodicity of muscular system development in the anatomical parts of carcasses has been found that largely due to functional loads as a result of which there is a redistribution of the muscular component in them. The biggest intensity of growth is typical for the muscle mass of the abdominal part, the least-for the muscles of the forearm and lower leg. A quarter of all muscles of carcasses accounted for the thigh in which the largest and most valuable in the nutrient framework are the biceps, quadriceps, semimembranosus, semitendinous muscles. The relative weight of the muscles located in the anatomical regions of the axial part of the skeleton with the age of animals has being increased and the muscles of the peripheral part of the skeleton-naturally has being decreased.

MicroRNA-mRNA network model in patients with achalasia.

Achalasia is a rare idiopathic disease with a complex etio-pathogenesis still unknown. This study aimed to identify microRNA (miRNA)-mRNA regulatory networks underlying achalasia. The investigation was performed in tissue specimens from 11 patients and five controls using the microarray technology followed by an integrated bioinformatics analysis. One hundred and six miRNAs were significantly up-regulated and 64 were down-regulated in achalasia patients. The expression of the most 10 differential expressed miRNAs (miR-122-5p, miR-133a-3p, miR-504-5p, miR-187-3p, miR-133b, miR-200c-3p, miR-375, miR-200b-5p, miR-200b-3p, and miR203a) was confirmed by droplet digital PCR in an independent cohort. The interactions between the significant miRNAs and their targets uncovered 14 miRNA-mRNA interacting pairs with experimentally predicted genes (ie, FN1, ROCK2, DPYSL2), and 35 pairs with not experimentally target genes (ie, SULF1, MRVI1, PRKG1); all genes were involved in immune cell trafficking, skeletal and muscular system development, nervous system development macro-processes. The mRNA-miRNA regulatory networks described in this study provide new insights in the genetic background of the disease, suggesting further investigations in novel pathogenic mechanisms.

Understanding the Development, Variations, and Defects of the Muscular System in Normal Human Embryos, Fetuses, and Newborns

There has been, until now, a limited knowledge on the development of the human muscular system, as most textbooks and atlases on human development described in detail the development of the skeletal system and other structures such as the internal organs without mentioning ‐ or doing it in a very brief way ‐ the muscular system. Moreover, within the few published works that did focus on the ontogeny of human muscles, most of them were restricted to a single muscle, a muscle group, a region, or a specific period of time (e.g. before 7 weeks of gestation). This makes the study of muscle anomalies, as well as of variations, very difficult due to the lack of good comparative models about normal development. We recently dissected 17 phenotypically ‘normal’ human newborns, fetuses and embryos between 7 and 39 weeks of development, and compared our results with the scarce literature available on the normal development of the muscular system in humans. Importantly, in the individuals dissected by us there was an indirect relationship between the ages of the fetuses and the number of seemingly fused (i.e. undifferentiated) muscles. That is, muscle anlagen in the early embryonic development often give rise to several muscles even after 7 weeks of gestation. This would contradict what is often described in the literature that by end of week 7 of gestation, all muscles resemble those of the adults (i.e. are differentiated). In addition, the number of the variations (i.e. phenotypes that deviate from the norm, within the ‘normal’ human population) per upper limbs dissected is significantly higher than the number of variations per lower limb studied, a pattern that is strikingly similar to that often reported in the literature about birth defects. Therefore, these and other results support Alberch's (1989) ill‐named “logic of monsters” theory that predicts a parallel between the variant phenotypes of the ‘normal’ populations and the defective phenotypes of genetically ‘abnormal’ individual due to the strong internal constraints that limit the number of possible outcomes. Furthermore, we present, for the first time, detailed data about the development of each head and limb human muscle from late embryonic stages to newborn configuration, and discuss the broader implications of these new data within a broad comparative and developmental framework.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Value of Osteoblast-Derived Exosomes in Bone Diseases.

The authors' purpose is to reveal the value of osteoblast-derived exosomes in bone diseases. Microvesicles from supernatants of mouse Mc3t3 were isolated by ultracentrifugation and then the authors presented the protein profile by proteomics analysis. The authors detected a total number of 1536 proteins by mass spectrometry and found 172 proteins overlap with bone database. The Ingenuity Pathway Analysis shows network of "Skeletal and Muscular System Development and Function, Developmental Disorder, Hereditary Disorder" and pathway about osteogenesis. EFNB1 and transforming growth factor beta receptor 3 in the network, LRP6, bone morphogenetic protein receptor type-1, and SMURF1 in the pathway seemed to be valuable in the exosome research of related bone disease. The authors' study unveiled the content of osteoblast-derived exosome and discussed valuable protein in it which might provide novel prospective in bone diseases research.

Gene Expression Profile During the Repair Process in a Rat Calvarial Bone Critical Size Defect

Bone is a complex tissue, providing support and protection while also adapting to the body's mechanical needs. In response to injury or fracture, bone has a significant capability for self‐repair and regeneration that requires the regulated expression of diverse families of genes that coordinate complex interactions among various cell types. Studies on bone non‐union have led to the critical size defect (CSD) theory, which states that as bone defects increase in size, a point will be reached where bone union will not occur and the bone will not heal spontaneously during the lifetime of the animal. CSDs fail to heal and regenerate bone, while noncritical defects produce an acceptable repair after bone loss. To improve outcome following significant bone loss we sought to identify genes differentially expressed between an 8 mm (CSD) and 4 mm (non‐CSD) size defects in a rat calvarial bone defect model. Rat whole genome microarrays were used to measure gene expression over the course of bone healing, and analysis of differentially expressed genes (DEGs) with Cytoscape® software revealed multiple temporal patterns of fold differences for DEGs. The patterns indicated that greatest number of differences occur at the earliest time point post‐injury (day 1), and starting at day 7 and continuing through day 21. Gene ontology and functional classification of genes altered in expression between the CSD and non‐CSD was conducted using Ingenuity Pathway Analysis software®. During the earliest (day 1,3) and later (day 14,21) times post injury, multiple DEGs and gene networks related to cell death and survival, cancer, connective tissue development and function, DNA Replication/recombination/repair, skeletal and muscular system development and function, and others, were identified. At the early time points TGF‐β1 and VEGFα signaling pathways are down modulated in CSD relative to non‐CSD include. Pathways that regulate movement of lymphocytes and activation of antigen presenting cells, as well as NFk‐B signaling, are upregulated at later times post‐ injury in CSD compared to non‐CSD. We conclude that genes and signaling pathways that promote healing and tissue homeostasis are suppressed in the CSD, in favor of activation of pro‐inflammatory signaling.Disclaimer: Research was conducted in compliance with the Animal Welfare Act, and all other Federal requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.Support or Funding InformationThis work was supported by funding from the United States Army Medical Research and Material Command Combat Casualty Care and Clinical and Rehabilitative Medicine Research Programs

Long non-coding RNA analysis of muscular responses to testosterone deficiency in Huainan male pigs.

Long non-coding RNAs (lncRNAs) participated in growth and development of skeletal muscle; however, little is known about their response to testosterone deficiency in porcine skeletal muscle. We compared lean mass related carcass traits and lncRNAs expression files in Longissimus dorsi (LD) muscle between intact and castrated Huainan male pigs. The results showed that castration significantly reduced eye muscle area and lean meat percentage (P<0.05), but increased the fat mass weight (P<0.05). Meanwhile, 8946 lncRNAs, including 6743 intergenic lncRNAs (lincRNAs), 498 anti-sense lncRNAs, and 1705 intronic lncRNAs, were identified in porcine LD, among which, 385 lncRNAs were considered as the differentially expressed candidates between intact groups and castrated groups (q-value<0.05). Functional analysis indicated that these differently expressed lncRNAs and their target genes were involved in the estrogen receptor signaling pathway and skeletal and muscular system development and function. We first detect porcine muscular lncRNA response to castration, and the results suggested that lncRNAs and their target genes participated in the regulation of testosterone deficiency-related skeletal muscle growth.

MicroRNA-mRNA regulatory networking fine-tunes the porcine muscle fiber type, muscular mitochondrial respiratory and metabolic enzyme activities

BackgroundMicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in diverse biological processes via regulation of gene expression including in skeletal muscles. In the current study, miRNA expression profile was investigated in longissimus muscle biopsies of malignant hyperthermia syndrome-negative Duroc and Pietrain pigs with distinct muscle metabolic properties in order to explore the regulatory role of miRNAs related to mitochondrial respiratory activity and metabolic enzyme activity in skeletal muscle.ResultsA comparative analysis of the miRNA expression profile between Duroc and Pietrain pigs was performed, followed by integration with mRNA profiles based on their pairwise correlation and computational target prediction. The identified target genes were enriched in protein ubiquitination pathway, stem cell pluripotency and geranylgeranyl diphosphate biosynthesis, as well as skeletal and muscular system development. Next, we analyzed the correlation between individual miRNAs and phenotypical traits including muscle fiber type, mitochondrial respiratory activity, metabolic enzyme activity and adenosine phosphate concentrations, and constructed the regulatory miRNA-mRNA networks associated with energy metabolism. It is noteworthy that miR-25 targeting BMPR2 and IRS1, miR-363 targeting USP24, miR-28 targeting HECW2 and miR-210 targeting ATP5I, ME3, MTCH1 and CPT2 were highly associated with slow-twitch oxidative fibers, fast-twitch oxidative fibers, ADP and ATP concentration suggesting an essential role of the miRNA-mRNA regulatory networking in modulating the mitochondrial energy expenditure in the porcine muscle. In the identified miRNA-mRNA network, a tight relationship between mitochondrial and ubiquitin proteasome system at the level of gene expression was observed. It revealed a link between these two systems contributing to energy metabolism of skeletal muscle under physiological conditions.ConclusionsWe assembled miRNA-mRNA regulatory networks based on divergent muscle properties between different pig breeds and further with the correlation analysis of expressed genes and phenotypic measurements. These complex networks relate to muscle fiber type, metabolic enzyme activity and ATP production and may contribute to divergent muscle phenotypes by fine-tuning the expression of genes. Altogether, the results provide an insight into a regulatory role of miRNAs in muscular energy metabolisms and may have an implication on meat quality and production.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2850-8) contains supplementary material, which is available to authorized users.

Genome-Wide H3K4me3 Analysis in Angus Cattle with Divergent Tenderness

Tenderness is one of the most important properties of meat quality, which is influenced by genetic and environmental factors. As an intensively studied epigenetic marker, histone methylation, occurring on arginine and lysine residues, has pivotal regulatory functions on gene expression. To examine whether histone methylation involves in beef tenderness variation, we analyzed the transcriptome and H3K4me3 enrichment profiles of muscle strips obtained from the longissimus dorsi (LD) of Angus steers previously classify to the tender or tough group. We first plotted a global bovine H3K4me3 map on chromosomes and called peak-enriched regions and genes. We found that majorities of H3K4me3 on genes were occupying the first intron and intergenic regions and its maps displayed similar patterns in tender and tough groups, with high H3K4me3 enrichment surrounding the transcription start site (TSS). We also explored the relationship of H3K4me3 and gene expression. The results showed that H3K4me3 enrichment is highly positively correlated with gene expression across the whole genome. Cluster analysis results confirmed the relationship of H3K4me3 enrichment and gene expression. By using a pathway-based approach in genes with H3K4me3 enrichment in promoter regions from the tender cluster, we revealed that those genes involved in the development of different tissues–connective tissue, skeletal and muscular system and functional tissues–; while in tough group those genes engaged in cell death, lipid metabolism and small molecule biochemistry. The results from this study provide a deep insight into understanding of the mechanisms of epigenetic regulations in meat quality and beef tenderness.

Essential Role of the Zinc Finger Transcription Factor Casz1 for Mammalian Cardiac Morphogenesis and Development

Chromosome 1p36 deletion syndrome is one of the most common terminal deletions observed in humans and is related to congenital heart disease (CHD). However, the 1p36 genes that contribute to heart disease have not been clearly delineated. Human CASZ1 gene localizes to 1p36 and encodes a zinc finger transcription factor. Casz1 is required for Xenopus heart ventral midline progenitor cell differentiation. Whether Casz1 plays a role during mammalian heart development is unknown. Our aim is to determine 1p36 gene CASZ1 function at regulating heart development in mammals. We generated a Casz1 knock-out mouse using Casz1-trapped embryonic stem cells. Casz1 deletion in mice resulted in abnormal heart development including hypoplasia of myocardium, ventricular septal defect, and disorganized morphology. Hypoplasia of myocardium was caused by decreased cardiomyocyte proliferation. Comparative genome-wide RNA transcriptome analysis of Casz1 depleted embryonic hearts identifies abnormal expression of genes that are critical for muscular system development and function, such as muscle contraction genes TNNI2, TNNT1, and CKM; contractile fiber gene ACTA1; and cardiac arrhythmia associated ion channel coding genes ABCC9 and CACNA1D. The transcriptional regulation of some of these genes by Casz1 was also found in cellular models. Our results showed that loss of Casz1 during mouse development led to heart defect including cardiac noncompaction and ventricular septal defect, which phenocopies 1p36 deletion syndrome related CHD. This suggests that CASZ1 is a novel 1p36 CHD gene and that the abnormal expression of cardiac morphogenesis and contraction genes induced by loss of Casz1 contributes to the heart defect.

Genetic association analysis of radiographic hip osteoarthritis with established loci for bone mineral density: data from the osteoarthritis initiative

Genetic association analysis of radiographic hip osteoarthritis with established loci for bone mineral density: data from the osteoarthritis initiative

Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia

BackgroundDespite the advances in our understanding of aging-associated behavioral decline, relatively little is known about how aging affects neural circuits that regulate specific behaviors, particularly the expression of genes in specific neural circuits during aging. We have addressed this by exploring a peptidergic neuron R15, an identified neuron of the marine snail Aplysia californica. R15 is implicated in reproduction and osmoregulation and responds to neurotransmitters such as acetylcholine, serotonin and glutamate and is characterized by its action potential bursts.ResultsWe examined changes in gene expression in R15 neurons during aging by microarray analyses of RNAs from two different age groups, mature and old animals. Specifically we find that 1083 ESTs are differentially regulated in mature and old R15 neurons. Bioinformatics analyses of these genes have identified specific biological pathways that are up or downregulated in mature and old neurons. Comparison with human signaling networks using pathway analyses have identified three major networks [(1) cell signaling, cell morphology, and skeletal muscular system development (2) cell death and survival, cellular function maintenance and embryonic development and (3) neurological diseases, developmental and hereditary disorders] altered in old R15 neurons. Furthermore, qPCR analysis of single R15 neurons to quantify expression levels of candidate regulators involved in transcription (CREB1) and translation (S6K) showed that aging is associated with a decrease in expression of these regulators, and similar analysis in three other neurons (L7, L11 and R2) showed that gene expression change during aging could be bidirectional.ConclusionsWe find that aging is associated with bidirectional changes in gene expression. Detailed bioinformatics analyses and human homolog searches have identified specific biological processes and human-relevant signaling pathways in R15 that are affected during aging. Evaluation of gene expression changes in different neurons suggests specific transcriptomic signature of single neurons during aging.

Genes Responsive to Low-Intensity Pulsed Ultrasound in MC3T3-E1 Preosteoblast Cells

Although low-intensity pulsed ultrasound (LIPUS) has been shown to enhance bone fracture healing, the underlying mechanism of LIPUS remains to be fully elucidated. Here, to better understand the molecular mechanism underlying cellular responses to LIPUS, we investigated gene expression profiles in mouse MC3T3-E1 preosteoblast cells exposed to LIPUS using high-density oligonucleotide microarrays and computational gene expression analysis tools. Although treatment of the cells with a single 20-min LIPUS (1.5 MHz, 30 mW/cm2) did not affect the cell growth or alkaline phosphatase activity, the treatment significantly increased the mRNA level of Bglap. Microarray analysis demonstrated that 38 genes were upregulated and 37 genes were downregulated by 1.5-fold or more in the cells at 24-h post-treatment. Ingenuity pathway analysis demonstrated that the gene network U (up) contained many upregulated genes that were mainly associated with bone morphology in the category of biological functions of skeletal and muscular system development and function. Moreover, the biological function of the gene network D (down), which contained downregulated genes, was associated with gene expression, the cell cycle and connective tissue development and function. These results should help to further clarify the molecular basis of the mechanisms of the LIPUS response in osteoblast cells.