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In developing melanocytes and in melanoma cells, multiple paralogs of the Activating-enhancer-binding Protein 2 family of transcription factors (TFAP2) contribute to expression of genes encoding pigmentation regulators, but their interaction with Microphthalmia transcription factor (MITF), a master regulator of these cells, is unclear. Supporting the model that TFAP2 facilitates MITF’s ability to activate expression of pigmentation genes, single-cell seq analysis of zebrafish embryos revealed that pigmentation genes are only expressed in the subset of mitfa -expressing cells that also express tfap2 paralogs. To test this model in SK-MEL-28 melanoma cells we deleted the two TFAP2 paralogs with highest expression, TFAP2A and TFAP2C , creating TFAP2 knockout ( TFAP2 -KO) cells. We then assessed gene expression, chromatin accessibility, binding of TFAP2A and of MITF, and the chromatin marks H3K27Ac and H3K27Me3 which are characteristic of active enhancers and silenced chromatin, respectively. Integrated analyses of these datasets indicate TFAP2 paralogs directly activate enhancers near genes enriched for roles in pigmentation and proliferation, and directly repress enhancers near genes enriched for roles in cell adhesion. Consistently, compared to WT cells, TFAP2 -KO cells proliferate less and adhere to one another more. TFAP2 paralogs and MITF co-operatively activate a subset of enhancers, with the former necessary for MITF binding and chromatin accessibility. By contrast, TFAP2 paralogs and MITF do not appear to co-operatively inhibit enhancers. These studies reveal a mechanism by which TFAP2 profoundly influences the set of genes activated by MITF, and thereby the phenotype of pigment cells and melanoma cells.

Objective: Rodlet cells produce secretions of glycoproteins in nature. This study investigated the microscopic morphology, histochemical and immunohistochemical reactions, and distribution of the rodlet cells in the gut of Binni fish (Mesopotamichthys sharpeyi). Materials and Methods: Thirty samples were obtained from the cranial, middle, and caudal por¬tions of Binni intestine immediately after being euthanized, fixed in Bouin’s solution for 18 h at 24°C, and had undergone routine histological processing, different conventional histochemical stains, and immunostaining with TNF-α and S100 protein antibody. Results: The intestine of Binni fish showed different stages of rodlet cells classified into three distinctive forms: vesicular, granular, and mature cells. Rodlet cells are poorly stained with hema¬toxylin and eosin. Their secretory granules have a weak positive reaction with periodic acid-Schiff (PAS) and Alcian blue (AB), and react positively to combined AB and PAS. Rodlet cells were stained lightly with Safranin O, observed pink in color by Giemsa stain, and showed reactivity to Masson’s and Mallory trichrome stains. Rodlet cells were immunostained positively against TNF-α and S100 antibodies, indicating that they have an immune function. Conclusions: Rodlet cells, with their neutral glycoprotein secretions, play a crucial role in the immunity of Binni fish intestine.

Commonly used pharmaceutical drugs might alter the epigenetic state of cells, leading to varying degrees of long-term repercussions to human health. To test this hypothesis, we cultured HEK-293 cells in the presence of 50 μM citalopram, a common antidepressant, for 30 days and performed whole-genome DNA methylation analysis using the NimbleGen Human DNA Methylation 3x720K Promoter Plus CpG Island Array. A total of 626 gene promoters, out of a total of 25,437 queried genes on the array (2.46%), showed significant differential methylation (p<0.01); among these, 272 were hypomethylated and 354 were hypermethylated in treated versus control. Using Ingenuity Pathway Analysis, we found that the chief gene networks and signaling pathways that are differentially regulated include those involved in nervous system development and function and cellular growth and proliferation. Genes implicated in depression, as well as genetic networks involving nucleic acid metabolism, small molecule biochemistry, and cell cycle regulation were significantly modified. Involvement of upstream regulators such as BDNF, FSH, and NFκB was predicted based on differential methylation of their downstream targets. The study validates our hypothesis that pharmaceutical drugs can have off-target epigenetic effects and reveals affected networks and pathways. We view this study as a first step towards understanding the long-term epigenetic consequences of prescription drugs on human health.

Amaç: Bu çalışmanın amacı, sağlıklı yenidoğanların antropometrik ölçümlerini yapmak ve ölçümlerin serum leptin ve insulin benzeri büyüme faktörü 1(IGF-1) düzeyleriyle ilişkisini araştırmaktır.Yöntemler: Toplam 113(55 erkek, 58 kız) sağlıklı yenidoğanda, ekstremite uzunlukları, deri kıvrım kalınlığı, vücut çevre ölçümleri uygun yöntemler kullanılarak ölçüldü. Serum leptin ve IGF-1 seviyelerine bakıldı.Bulgular: Antropometrik ölçümlerden vücut kitle indeksi, vücut ağırlığı ve suprailiac deri kıvrım kalınlığı ile serum leptin seviyesi arasında orta düzeyde pozitif korelasyon saptandı (p0.05).Sonuç: Bebeklerin antropometrik ölçümleri gelecekteki büyüme ve gelişme düzeyleri konusunda rehberlik edecektir. Leptin büyüme üzerine etkili bir hormondur Objective: The aim of the present study is to determine anthropometric measurements of a group of healthy newborns and evaluate their association with the serum levels of leptin and insulin-like growth factor 1(IGF-1).Methods: Extremity lengths, skinfold thickness, body circumference measurements of 113 heathy newborns were taken by appropriate methods. Of the total 113 newborns, 55 were male and 58 were female. Serum leptin and IGF-1 levels were measured.Results: Leptin levels had moderately positive correlations with body mass index (BMI), weight and suprailiac skinfold thickness (p<0.05). There was no significant relationship between anthropometric measurements and IGF-1 levels (p>0.05).Conclusion: Anthropometric measurements of newborns will be of guidance for the growth and development of their future life. J Clin Exp Invest 2015; 6 (3): 214-219Key words: Anthropometry, newborn, leptin, insulin-like growth factor 1(IGF-1)

Background/Aims: Excessive lipid accumulation in hepatocytes is a critical cause of metabolic dysfunction-associated steatotic liver disease (MASLD) progression. Ankyrin repeat and SOCS box protein 3 (ASB3) is an E3 ubiquitin ligase that mediates diverse disease processes; however, the direct substrates of ASB3 in lipid metabolism and its role in MASLD remain unexplored.Methods: We generated ASB3 knockout mice fed a high-fat diet to induce MASLD. Oxygen consumption and fatty acid oxidation (FAO) were used to assess lipid metabolism. LC-MS/MS and IP were used to verify the ASB3 target protein. Correlation analysis was conducted on the cohort of MASLD patients vs. the control group.Results: Loss of the ASB3 E3 ubiquitin ligase in hepatocytes strengthens mitochondrial FAO, thereby influencing energy consumption to decrease triglyceride storage and lipid accumulation. Quantitative lysine ubiquitination proteomics revealed that ASB3 directly mediated the ubiquitin levels at two sites (K180 and K639) in carnitine palmitoyl transferase 1A (CPT1A), a rate-limiting enzyme of FAO, to induce CPT1A degradation. Moreover, both constitutive and hepatocyte-specific ASB3 knockout enhance FAO and delay lipid accumulation, liver steatosis, and MASLD progression in a CPT1A-dependent manner. Hepatic ASB3 deficiency also delays fibrosis in MASLD. Analysis of public databases and liver tissue samples from MASLD patients revealed that ASB3 was highly expressed in MASLD patients and was negatively correlated with CPT1A.Conclusions: Our study reveals the key roles of ASB3 in the development of MASLD and suggests a novel therapeutic potential for MASLD.

Specimen preservation is an essential factor in gross anatomical study of the brain and spinal cord. Forced impregnation of the specimen using polymer, or plastination, is to date one of the best specimen preparation procedures. This study aimed to study the possibility of staining whole brain specimen using Sudan Red III dye prior to plastination. Dog brains were divided into 3 groups each stained with the dye for 1, 2 and 3 months, respectively. The stained specimens were then dissected to reveal the staining of deep structures before undergoing the plastination procedure. After the experiment we found that Sudan Red clearly stained the fiber tracts making it differentiable from the gray matter. However, after the strong acetone dehydration steps during the plastination procedure, most of the dye were thinned down in some specimen whereas in a few it was enough to differentiate the gray from white matter although not as clearly as prior to the procedure. Hence, Sudan Red III may not be a reliable dye of choice when followed by plastination. [PUBLICATION ABSTRACT]

This study was carried out to observe morphological changes of swamp buffalo endometrium at follicular and mid-luteal phases. Uterine horns were collected from female buffaloes at a local abattoir and the selected estrous stages were categorized into the follicular (n = 10) and mid-luteal (n = 10) phases. General histology and histomorphometry were examined under light microscope (LM) whereas a scanning electron microscope (SEM) was used to study surface epithelial changes. The results showed that the height of the endometrial epithelium, the number of superficial endometrial glands and the number of capillaries were significantly greater (p < 0.05) at the follicular phase. By SEM examination, the ciliated and secretory cells with different patterns, i.e. abundant microvilli on the apical part or secretory protrusion in various degrees, distinctly increased at the follicular phase. In the meantime, numerous secretory cells with stubby microvilli were covered throughout the endometrial surface with secretory vesicles on endometrial glandular orifices at the mid-luteal phase in which the ciliated cells were sparsely seen. It was concluded that the swamp buffalo endometrium obviously revealed modifications during the estrous cycle for physiological events, i.e. sperm transport, early embryonic development and implantation. [PUBLICATION ABSTRACT]

A central paradigm in conservation biology is that population bottlenecks reduce genetic diversity and population viability. In an era of biodiversity loss and climate change, understanding the determinants and consequences of bottlenecks is therefore an important challenge. However, as most studies focus on single species, the multitude of potential drivers and the consequences of bottlenecks remain elusive. Here, we combined genetic data from over 11,000 individuals of 30 pinniped species with demographic, ecological and life history data to evaluate the consequences of commercial exploitation by 18th and 19th century sealers. We show that around one third of these species exhibit strong signatures of recent population declines. Bottleneck strength is associated with breeding habitat and mating system variation, and together with global abundance explains much of the variation in genetic diversity across species. Overall, bottleneck intensity is unrelated to IUCN status, although the three most heavily bottlenecked species are endangered. Our study reveals an unforeseen interplay between human exploitation, animal biology, demographic declines and genetic diversity.

Background - Sex determination relies on a hierarchically structured network of genes, and is one of the most plastic processes in evolution. The evolution of sex-determining genes within a network, by neo- or sub-functionalization, also requires the regulatory landscape to be rewired to accommodate these novel gene functions. We previously showed that in medaka fish, the regulatory landscape of the master male-determining gene dmrt1bY underwent a profound rearrangement, concomitantly with acquiring a dominant position within the sex-determining network. This rewiring was brought about by the exaptation of a transposable element (TE) called Izanagi, which is co-opted to act as a silencer to turn off the dmrt1bY gene after it performed its function in sex determination. Results - We now show that a second TE, Rex1, has been incorporated into Izanagi. The insertion of Rex1 brought in a preformed regulatory element for the transcription factor Sox5, which here functions in establishing the temporal and cell-type-specific expression pattern of dmrt1bY. Mutant analysis demonstrates the importance of Sox5 in the gonadal development of medaka, and possibly in mice, in a dmrt1bY-independent manner. Moreover, Sox5 medaka mutants have complete female-to-male sex reversal. Conclusions - Our work reveals an unexpected complexity in TE-mediated transcriptional rewiring, with the exaptation of a second TE into a network already rewired by a TE. We also show a dual role for Sox5 during sex determination: first, as an evolutionarily conserved regulator of germ-cell number in medaka, and second, by de novo regulation of dmrt1 transcriptional activity during primary sex determination due to exaptation of the Rex1 transposable element.