Smyd3 Is Required for the Development of Cardiac and Skeletal Muscle in Zebrafish

Modifications of histone tails are involved in the regulation of a wide range of biological processes including cell cycle, cell survival, cell division, and cell differentiation. Among the modifications, histone methylation plays a critical role in cardiac and skeletal muscle differentiation. In our earlier studies, we found that SMYD3 has methyltransferase activity to histone H3 lysine 4, and that its up-regulation is involved in the tumorigenesis of human colon, liver, and breast. To clarify the role of Smyd3 in development, we have studied its expression patterns in zebrafish embryos and the effect of its suppression on development using Smyd3-specific antisense morpholino-oligonucleotides. We here show that transcripts of smyd3 were expressed in zebrafish embryos at all developmental stages examined and that knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure. In addition, these phenotypes were associated with abnormal expression of three heart-chamber markers including cmlc2, amhc and vmhc, and abnormal expression of myogenic regulatory factors including myod and myog. These data suggest that Smyd3 plays an important role in the development of heart and skeletal muscle

Stochastic Models of Lymphocyte Proliferation and Death

Quantitative understanding of the kinetics of lymphocyte proliferation and death upon activation with an antigen is crucial for elucidating factors determining the magnitude, duration and efficiency of the immune response. Recent advances in quantitative experimental techniques, in particular intracellular labeling and multi-channel flow cytometry, allow one to measure the population structure of proliferating and dying lymphocytes for several generations with high precision. These new experimental techniques require novel quantitative methods of analysis. We review several recent mathematical approaches used to describe and analyze cell proliferation data. Using a rigorous mathematical framework, we show that two commonly used models that are based on the theories of age-structured cell populations and of branching processes, are mathematically identical. We provide several simple analytical solutions for a model in which the distribution of inter-division times follows a gamma distribution and show that this model can fit both simulated and experimental data. We also show that the estimates of some critical kinetic parameters, such as the average inter-division time, obtained by fitting models to data may depend on the assumed distribution of inter-division times, highlighting the challenges in quantitative understanding of cell kinetics

Hypovitaminosis D is associated with negative outcome in dogs with protein losing enteropathy: a retrospective study of 43 cases

Abstract Background Hypovitaminosis D has previously been shown to be prevalent amongst dogs with protein losing enteropathy (PLE). The hypothesis of this study was that Low 25-hydroxyvitamin D (25(OH) D) serum concentrations could be a risk factor for negative outcome in dogs with PLE. Forty-three dogs diagnosed with PLE (2005–2014) and which serum Vitamin D serum concentrations were collected and archived at −80 Degrees C were analyzed. Post-diagnostic communication with referring veterinarians was made to determine outcome of PLE dogss: Dogs which died due to PLE within 4 months after diagnosis (negative outcome group, n = 22) and dogs alive or which died due to another disease at the end point of the study (1 year after diagnosis, good outcome group, n = 21). Serum samples taken at the time of diagnosis were analysed for ionized calcium (iCa) concentrations and serum 25(OH) D concentration. Results Clinical (CCECAI) scores, age at PLE diagnosis, and iCa concentrations were not significantly different between dog groups. A significantly greater (p < 0.001) number of PLE dogs treated with hydrolyzed or elimination diet alone showed good outcome as compared to the PLE negative outcome group. Median serum 25(OH) D concentration was significantly (p = 0.017) lower in dogs with negative outcome versus PLE dogs with good outcome. Using logistic regression analysis, 25(OH) D serum concentration was shown to be a statistically significant factor for outcome determination. Cox regression analysis yielded a hazard ratio of 0.974 (95% CI 0.949, 0.999) per each one nmol/l increase in serum 25(OH) D concentration. Conclusions Low serum 25(OH) D concentration in PLE dogs was significantly associated with poor outcome. Further studies are required to investigate the clinical efficacy of Vitamin D (cholecalciferol) as a potential therapeutic agent for dogs with PLE

Exploring the Caffeine-Induced Teratogenicity on Neurodevelopment Using Early Chick Embryo

Caffeine consumption is worldwide. It has been part of our diet for many centuries; indwelled in our foods, drinks, and medicines. It is often perceived as a “legal drug”, and though it is known to have detrimental effects on our health, more specifically, disrupt the normal fetal development following excessive maternal intake, much ambiguity still surrounds the precise mechanisms and consequences of caffeine-induced toxicity. Here, we employed early chick embryos as a developmental model to assess the effects of caffeine on the development of the fetal nervous system. We found that administration of caffeine led to defective neural tube closures and expression of several abnormal morphological phenotypes, which included thickening of the cephalic mesenchymal tissues and scattering of somites. Immunocytochemistry of caffeine-treated embryos using neural crest cell markers also demonstrated uncharacteristic features; HNK1 labeled migratory crest cells exhibited an incontinuous dorsal-ventral migration trajectory, though Pax7 positive cells of the caffeine-treated groups were comparatively similar to the control. Furthermore, the number of neurons expressing neurofilament and the degree of neuronal branching were both significantly reduced following caffeine administration. The extent of these effects was dose-dependent. In conclusion, caffeine exposure can result in malformations of the neural tube and induce other teratogenic effects on neurodevelopment, although the exact mechanism of these effects requires further investigation

Functional Analysis of Conserved Non-Coding Regions Around the Short Stature hox Gene (shox) in Whole Zebrafish Embryos

Background: Mutations in the SHOX gene are responsible for Leri-Weill Dyschondrosteosis, a disorder characterised by mesomelic limb shortening. Recent investigations into regulatory elements surrounding SHOX have shown that deletions of conserved non-coding elements (CNEs) downstream of the SHOX gene produce a phenotype indistinguishable from Leri-Weill Dyschondrosteosis. As this gene is not found in rodents, we used zebrafish as a model to characterise the expression pattern of the shox gene across the whole embryo and characterise the enhancer domains of different CNEs associated with this gene. Methodology/Principal Findings: Expression of the shox gene in zebrafish was identified using in situ hybridization, with embryos showing expression in the blood, putative heart, hatching gland, brain pharyngeal arch, olfactory epithelium, and fin bud apical ectodermal ridge. By identifying sequences showing 65% identity over at least 40 nucleotides between Fugu, human, dog and opossum we uncovered 35 CNEs around the shox gene. These CNEs were compared with CNEs previously discovered by Sabherwal et al. ,resulting in the identification of smaller more deeply conserved sub-sequence. Sabherwal et al.’s CNEs were assayed for regulatory function in whole zebrafish embryos resulting in the identification of additional tissues under the regulatory control of these CNEs. Conclusion/Significance: Our results using whole zebrafish embryos have provided a more comprehensive picture of the expression pattern of the shox gene, and a better understanding of its regulation via deeply conserved noncoding elements. In particular, we identify additional tissues under the regulatory control of previously identified SHOX CNEs. We also demonstrate the importance of these CNEs in evolution by identifying duplicated shox CNEs and more deeply conserved sub-sequences within already identified CNEs

FishNet: an online database of zebrafish anatomy

Background: Over the last two decades, zebrafish have been established as a genetically versatile model system for investigating many different aspects of vertebrate developmental biology. With the credentials of zebrafish as a developmental model now well recognized, the emerging new opportunity is the wider application of zebrafish biology to aspects of human disease modelling. This rapidly increasing use of zebrafish as a model for human disease has necessarily generated interest in the anatomy of later developmental phases such as the larval, juvenile, and adult stages, during which many of the key aspects of organ morphogenesis and maturation take place. Anatomical resources and references that encompass these stages are non-existent in zebrafish and there is therefore an urgent need to understand how different organ systems and anatomical structures develop throughout the life of the fish. Results: To overcome this deficit we have utilized the technique of optical projection tomography to produce three-dimensional (3D) models of larval fish. In order to view and display these models we have created FishNet http://www.fishnet.org.au, an interactive reference of zebrafish anatomy spanning the range of zebrafish development from 24 h until adulthood. Conclusion: FishNet contains more than 36 000 images of larval zebrafish, with more than 1 500 of these being annotated. The 3D models can be manipulated on screen or virtually sectioned. This resource represents the first complete embryo to adult atlas for any species in 3D

Lbx2 regulates formation of myofibrils

<p>Abstract</p> <p>Background</p> <p>Skeletal muscle differentiation requires assembly of contractile proteins into organized myofibrils. The <it>Drosophila ladybird homeobox </it>gene (<it>lad</it>) functions in founder cells of the segmental border muscle to promote myoblast fusion and muscle shaping. Tetrapods have two homologous genes (<it>Lbx</it>). Lbx1 functions in migration and/or proliferation of hypaxial myoblasts, whereas the function of Lbx2 is poorly understood.</p> <p>Results</p> <p>To elucidate the role of Lbx in vertebrate myogenesis, we examined Lbx function in zebrafish. Zebrafish <it>lbx2 </it>transcripts appear in newly formed paraxial mesoderm and become restricted to adaxial cells, precursors of slow muscle. Slow muscles lose <it>lbx2 </it>expression as they differentiate, while a subset of differentiating fast muscle cells transiently expresses <it>lbx2</it>. Fin and hyoid muscle express <it>lbx2 </it>later. In contrast, <it>lbx1b </it>expression first appears lateral to the somites at late segmentation stages and is later restricted to fin muscle. Morpholino knockdown of Lbx1b and Lbx2 suppresses hypaxial muscle development. Moreover, knockdown of Lbx2 results in malformation of muscle fibers and reduced fusion of fast precursors, although no obvious effects on induction or specification are observed. Expression of myofilament genes, including <it>actin </it>and <it>myosin</it>, requires the engrailed repressor domain of Lbx2.</p> <p>Conclusion</p> <p>Our results elucidate a new function of Lbx2 as a regulator of myofibril formation.</p

Visible and Invisible Trends in Black Men's Health: Pitfalls and Promises for Addressing Racial, Ethnic, and Gender Inequities in Health

Over the past two decades, there has been growing interest in improving black men's health and the health disparities affecting them. Yet, the health of black men consistently ranks lowest across nearly all groups in the United States. Evidence on the health and social causes of morbidity and mortality among black men has been narrowly concentrated on public health problems (e.g., violence, prostate cancer, and HIV/AIDS) and determinants of health (e.g., education and male gender socialization). This limited focus omits age-specific leading causes of death and other social determinants of health, such as discrimination, segregation, access to health care, employment, and income. This review discusses the leading causes of death for black men and the associated risk factors, as well as identifies gaps in the literature and presents a racialized and gendered framework to guide efforts to address the persistent inequities in health affecting black men

Animal abuse and intimate partner violence: researching the link and its significance in Ireland - a veterinary perspective

Research on domestic violence has established a substantial association between intimate partner abuse and the abuse of children within the home. It is only recently however, that researchers have demonstrated the correlation between non-accidental injury in animals, and abuse of women by their intimate male partners. A growing body of evidence suggests that animal abuse can be an early indicator for other forms of violent behaviour. This research includes the responses of a sample of 23 women using refuge services in the Republic of Ireland. It investigates the connection between domestic violence and animal abuse, and ascertains if there is sufficient support service for animals and people relevant to domestic abuse. In the survey population, 57% of women reported witnessing one or more forms of abuse, or threats of abuse, of their pets. Five of which were reported to have resulted in the death of the pet. Eighty seven per cent of women felt a facility to accommodate pets would have made their decision to leave the family home easier. Four women disclosed that lack of such a service and concern for the welfare of their companion animals caused them to remain in their abusive relationships for longer than they felt appropriate. Nine families placed pets in the care of family or friends, one woman is unaware of the fate of her pet, while the pets of six families remained with the abusive male after his partner entered a refuge. The majority of women felt unable to talk to anyone about their fears for their pets' welfare. Many felt that there is no service which can provide temporary accommodation for womens' pets while they are in refuge. The results obtained support those found elsewhere in larger studies in the USA and UK, and demonstrate an association of animal abuse in households where there is reported domestic violence

Structure and phase stability of nanocrystalline Ce1−xLnxO2−x/2−δ (Ln = Yb, Lu) in oxidizing and reducing atmosphere

The structure and phase evolution of nanocrystalline Ce1−xLnxO2−x/2−δ (Ln = Yb, Lu, x = 0 − 1) oxides upon heating in H2 was studied for the first time. Up to 950 °C the samples were single-phase, with structure changing smoothly with x from fluorite type (F) to bixbyite type (C). For the Lu-doped samples heated at 1100 °C in the air and H2, phase separation into coexisting F- and C-type structures was observed for ~0.40 < x < ~0.70 and ~0.25 < x < ~0.70, respectively. It was found also that addition of Lu3+ and Yb3+ strongly hinders the crystallite growth of ceria during heat treatment at 800 and 950 °C in both atmospheres. Valency of Ce and Yb in Ce0.1Lu0.9O1.55−δ and Ce0.95Yb0.05O1.975−δ samples heated at 1100 °C was studied by XANES and magnetic measurements. In the former Ce was dominated by Ce4+, with small contribution of Ce3+ after heating in H2. In the latter, Yb existed exclusively as 3+ in both O2 and H2