A novel case of homozygous PAX1 mutation associated with hypoparathyroidism.

Unlabelled: The PAX1 gene plays an important role in the development of the parathyroid glands and the thymus. Mouse knockout models of PAX1, PAX3, and PAX9 have been found to have hypoplastic or absent parathyroid glands. To our knowledge, there are no reported cases of PAX1-associated hypoparathyroidism in humans.

Left-sided valvular heart disease and retinopathy in a 38-year-old woman with attenuated mucopolysaccharidosis: a case report.

Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by deficient levels and/or activity of glycosaminoglycan (GAG)-degradative enzymes. MPS are characterized by accumulation of the mucopolysaccharides heparan sulfate, dermatan sulfate, keratan sulfate, or chondroitin sulfate in tissues. We report the case of a 38-year-old woman with a history of joint restriction and retinitis pigmentosa who developed bivalvular heart failure requiring surgery.

Identification of dominant optic atrophy following reanalysis of clinical exome sequencing.

Purpose: To highlight the importance of the utility of clinical exome sequencing, and show how it led to the diagnosis of nonsyndromic autosomal dominant optic atrophy arising from an autosomal dominant variant in

Observations: A healthy father and daughter of East African heritage experienced the onset of vision loss in the first decade of life due to optic atrophy. No additional neurologic or neuroimaging abnormalities were detected. Clinical exome sequencing was initially performed and provided a negative result.

Update on Clinically Relevant Genetic Testing in Pediatric Dermatology.

Clinical genetic testing enables the detection of specific gene mutations and variants that predispose individuals and their family members to disease. In recent years, tremendous strides have been made in the variety of clinically useful tests. Targeted testing for specific mutations that cause well-known syndromes enables the efficient diagnosis of genetic diseases with cutaneous manifestations.

-2 Regulates Liver Fibrosis through the TGF-β Signaling Pathway.

Transforming growth factor-β (TGF-β) activates hepatic stellate cells (HSCs), which drive liver fibrosis via the production and deposition of extracellular matrix (ECM). We aimed to elucidate the mechanistic role of -2 (SULF2) in liver fibrosis. To this end, we induced liver fibrosis in wild-type (WT) and SULF2 knockout (-KO) mice (6-8 weeks-old) via bile duct ligation (BDL), intraperitoneal injection of carbon tetrachloride (CCl) or thioacetamide (TAA).

Knockout of sulfatase 2 is associated with decreased steatohepatitis and fibrosis in a mouse model of nonalcoholic fatty liver disease.

Sulfatase 2 (SULF2) is a heparan sulfate editing enzyme that regulates the milieu of growth factors and cytokines involved in a variety of cellular processes. We used a murine model of diet-induced steatohepatitis to assess the effect of SULF2 downregulation on the development of nonalcoholic steatohepatitis (NASH) and liver fibrosis. Wild-type B6;129 mice (WT) and -knockout B6;129P2-SULF2 mice (KO) were fed a fast-food diet (FFD) rich in saturated fats, cholesterol, and fructose or a standard chow diet (SC) ad libitum for 9 mo.

The extracellular sulfatase SULF2 promotes liver tumorigenesis by stimulating assembly of a promoter-looping GLI1-STAT3 transcriptional complex.

The expression of the extracellular sulfatase SULF2 has been associated with increased hepatocellular carcinoma (HCC) growth and poor patient survival. However, the molecular mechanisms underlying SULF2-associated tumor growth remain unclear. To address this gap, here we developed a transgenic mouse overexpressing in hepatocytes under the control of the transthyretin promoter.

Differentiation of hepatocyte-like cells from human pluripotent stem cells using small molecules.

A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells.

Age-associated changes in the ecological niche: implications for mesenchymal stem cell aging.

Adult stem cells are critical for organ-specific regeneration and self-renewal with advancing age. The prospect of being able to reverse tissue-specific post-injury sequelae by harvesting, culturing and transplanting a patient's own stem and progenitor cells is exciting. Mesenchymal stem cells have emerged as a reliable stem cell source for this treatment modality and are currently being tested in numerous ongoing clinical trials.

Nuclear cardiac troponin and tropomyosin are expressed early in cardiac differentiation of rat mesenchymal stem cells.

Nuclear actin - which is immunologically distinct from cytoplasmic actin - has been documented in a number of differentiated cell types, and cardiac isoforms of troponin I (cTnI) and troponin T (cTnT) have been detected in association with nuclei of adult human cardiac myocytes. It is not known whether these and related proteins are present in undifferentiated stem cells, or when they appear in cardiomyogenic cells following differentiation. We first tested the hypothesis that nuclear actin and cardiac isoforms of troponin C (cTnC) and tropomyosin (cTm) are present along with cTnI and cTnT in nuclei of isolated, neonatal rat cardiomyocytes in culture.

Age-related changes in rat bone-marrow mesenchymal stem cell plasticity.

Background: The efficacy of adult stem cells is known to be compromised as a function of age. This therefore raises questions about the effectiveness of autologous cell therapy in elderly patients.

Results: We demonstrated that the expression profile of stemness markers was altered in BM-MSCs derived from old rats.

Minority youth access to tobacco: a neighborhood analysis of underage tobacco sales.

The geographic and racial-ethnic inequities in health in the US are concerning, and their reduction is a priority for the national health initiative: Health People 2010. Though voluntary, life-style factors, such as smoking, are partially a cause of unevenness in health outcomes, targeting tobacco to minority youth raises questions about the extent to which behaviors are exacerbated by the local retail environment. In this case study, a GIS analysis of neighborhoods where businesses sold tobacco to minors was conducted with 2005 Florida Department of Health, and US census data, finding that in Miami, underage tobacco sales were significantly more concentrated in Hispanic majority neighborhoods.