Linking SNPs to CAG repeat length in Huntington's disease patients

Allele-specific silencing using small interfering RNAs targeting heterozygous single-nucleotide polymorphisms (SNPs) is a promising therapy for human trinucleotide repeat diseases such as Huntington's disease. Linking SNP identities to the two HTT alleles, normal and disease-causing, is a prerequisite for allele-specific RNA interference. Here we describe a method, SNP linkage by circularization (SLiC), to identify linkage between CAG repeat length and nucleotide identity of heterozygous SNPs using Huntington's disease patient peripheral blood samples.     

Light and scanning electron microscopic study of the tongue in the estuarine dolphin (Sotalia guianensis van Bénéden, 1864)

The importance of the tongue during feeding, and the limited information on the tongue of most aquatic mammals led us to investigate its morphological aspects in sexually immature and mature Sotalia guianensis. Six tongues were measured and photo-documented after their removal from the oral cavity. The samples were divided into rostral, middle, and caudal regions, and examined using light microscopy and scanning electron microscopy (S.E.M.). Sotalia guianensis tongue presented lateral grooves from the apex to the middle portion, while the anterolateral region presented marginal papillae. Histological characteristics revealed the presence of a keratinized stratified epithelium, salivary glands in the middle and caudal portions of the tongue, and filiform papillae in the caudal region. S.E.M. images revealed the presence of filiform papillae and ducts of salivary glands in the middle and caudal portions of the tongue. We can conclude that the characteristics found in this study may reflect an adaptation to changes in diet after weaning.     

Performance in working memory and attentional control is associated with the rs2180619 SNP in the CNR1 gene

Individual differences in cognitive performance are partly dependent, on genetic polymporhisms. One of the single‐nucleotide polymorphisms (SNP) of the CNR1 gene, which codes for cannabinoid receptor 1 (CB1R), is the rs2180619, located in a regulatory region of this gene (6q14–q15). The alleles of the rs2180619 are A > G; the G allele has been associated with addiction and high levels of anxiety (when the G allele interacts with the SS genotype of the 5‐HTTLPR gene). However, GG genotype is observed also in healthy subjects. Considering G allele as risk for ‘psychopathological conditions’, it is possible that GG healthy subjects do not be addicted or anxious, but would have reduced performance, compared to AA subjects, in attentional control and working memory processing. One hundred and sixty‐four healthy young Mexican‐Mestizo subjects (100 women and 64, men; mean age: 22.86 years, SD=2.72) participated in this study, solving a task where attentional control and working memory were required. GG subjects, compared to AA subjects showed: (1) a general lower performance in the task (P = 0.02); (2) lower performance only when a high load of information was held in working memory (P = 0.02); and (3) a higher vulnerability to distractors (P = 0.03). Our results suggest that, although the performance of GG subjects was at normal levels, a lower efficiency of the endocannabinoid system, probably due to a lowered expression of CB1R, produced a reduction in the performance of these subjects when attentional control and working memory processing is challenged .     

The Association between Individual and Combined Components of Metabolic Syndrome and Chronic Kidney Disease among African Americans: The Jackson Heart Study

Introduction

Approximately 26.3 million people in the United States have chronic kidney disease and many more are at risk of developing the condition. The association between specific metabolic syndrome components and chronic kidney disease in African American individuals is uncertain.

Methods

Baseline data from 4,933 participants of the Jackson Heart Study were analyzed. Logistic regression models were used to estimate the odds and 95% confidence intervals of chronic kidney disease associated with individual components, metabolic syndrome, the number of components, and specific combinations of metabolic syndrome components.

Results

Metabolic syndrome was common with a prevalence of 42.0%. Chronic kidney disease was present in 19.4% of participants. The prevalence of metabolic components was high: elevated blood pressure (71.8%), abdominal obesity (65.8%), low fasting high density lipoprotein cholesterol (37.3%), elevated fasting glucose (32.2%) and elevated triglycerides (16.2%). Elevated blood pressure, triglycerides, fasting blood glucose, and abdominal obesity were significantly associated with increased odds of chronic kidney disease. Participants with metabolic syndrome had a 2.22-fold (adjusted odds ratio (AOR) 2.22; 95% CI, 1.78–2.78) increase in the odds of chronic kidney disease compared to participants without metabolic syndrome. The combination of elevated fasting glucose, elevated triglycerides, and abdominal obesity was associated with the highest odds for chronic kidney disease (AOR 25.11; 95% CI, 6.94–90.90).

Conclusion

Metabolic syndrome as well as individual or combinations of metabolic syndrome components are independently associated with chronic kidney disease in African American adults.     

Transforming Growth Factor-β1 Downregulates Vascular Endothelial Growth Factor-D Expression in Human Lung Fibroblasts via the Jun NH2-Terminal Kinase Signaling Pathway

Vascular endothelial growth factor (VEGF)-D, a member of the VEGF family, induces both angiogenesis and lymphangiogenesis by activating VEGF receptor-2 (VEGFR-2) and VEGFR-3 on the surface of endothelial cells. Transforming growth factor (TGF)-β1 has been shown to stimulate VEGF-A expression in human lung fibroblast via the Smad3 signaling pathway and to induce VEGF-C in human proximal tubular epithelial cells. However, the effects of TGF-β1 on VEGF-D regulation are unknown. To investigate the regulation of VEGF-D, human lung fibroblasts were studied under pro-fibrotic conditions in vitro and in idiopathic pulmonary fibrosis (IPF) lung tissue. We demonstrate that TGF-β1 downregulates VEGF-D expression in a dose- and time-dependent manner in human lung fibroblasts. This TGF-β1 effect can be abolished by inhibitors of TGF-β type I receptor kinase and Jun NH₂-terminal kinase (JNK), but not by Smad3 knockdown. In addition, VEGF-D knockdown in human lung fibroblasts induces G1/S transition and promotes cell proliferation. Importantly, VEGF-D protein expression is decreased in lung homogenates from IPF patients compared with control lung. In IPF lung sections, fibroblastic foci show very weak VEGF-D immunoreactivity, whereas VEGF-D is abundantly expressed within alveolar interstitial cells in control lung. Taken together, our data identify a novel mechanism for downstream signal transduction induced by TGF-β1 in lung fibroblasts, through which they may mediate tissue remodeling in IPF.     

Environmentally induced variation in fecundity compensation in the morph-biased male-sterile distylous shrub Erythroxylum havanense (Erythroxylaceae)

The evolution of male-sterile individuals in hermaphroditic species represents the first step in the evolution of sex specialization. For male-sterile individuals to persist they must have some fitness advantage that compensates for their loss of the male function. Female fecundity also depends on environmental factors as those determining the likelihood of pollination and fertilization. Here we assessed the effects of both male sterility and reproductive synchrony (an environmentally affected trait) on the magnitude of female compensation of Erythroxylum havanense, a distylous shrub with morph-biased male sterility. In vitro measurements of pollen germination showed that thrums were more male sterile than pins. The compensatory advantage of thrums changed by a factor of five depending on flowering synchrony. Flowering in synchrony with the population increased fruit production in both morphs. However, because pins that flowered out of synchrony produced almost no fruits, the reproductive compensation of thrums was higher in these circumstances. Because the magnitude of compensation is frequently considered as a key factor in the evolution of sex specialization, the environmentally induced variation in the magnitude of the reproductive compensation of thrum plants may have profound effects on the evolutionary dynamics of the reproductive system of E. havanense.