GALNT2 mRNA levels are associated with serum triglycerides in humans

Atherogenic dyslipidemia, characterized by high triglycerides (TG) and low high density lipoprotein (HDL)-cholesterol levels, is a feature of patients with insulin resistance, obesity, and type 2 diabetes (T2D) [1] and plays a major role in shaping the risk of cardiovascular disease. Both TG and HDL-cholesterol serum concentrations are under the control of both environmental factors and up to 95 genetic loci, unraveled by a very large genome-wide association study (GWAs) in approximately 100,000 individuals [2]. Among these loci is GALNT2, which encode for ppGal-NAc-T2, involved in O-linked glycosylation. Similarly, studies in rodents have shown that liver GALNT2 expression modulates HDL-cholesterol concentrations [2]. Based on such studies, it is conceivable that GALNT2 expression changes play a role on TG and/or HDL-cholesterol levels. To gain further insights about this hypothesis, GALNT2 expression was measured in peripheral white blood cells (PWBC), from 224 individuals with a wide range of TG and HDL-cholesterol levels, as well as other metabolic parameters and clinical conditions

Colour variation of the Maltese wall lizards (Podarcis filfolensis) at population and individual levels in the Linosa island

AbstractThe research on animal colouration has always been of great interest for biologists but since the last decades it has grown exponentially thanks to multidisciplinary approaches. Animals have found several ways to deal with the camouflage/communication trade-off in colouration, leading to the evolution of alternative patterns of variation of colourations at different levels including signal partitioning and spatial resolution of colouration. In this paper we analyse the variability of dorsal and ventral colouration in males and females of Maltese wall lizards in three populations on Linosa. We collected high-resolution digital images of dorsal, ventral and throat colouration from 61 lizards (32 males and 29 females). We showed that the colouration differs among sexes and body regions within the same individual. Colourations are also variable among individuals within population, as well as among different populations across the Island. Finally, we detected a lizard's colouration shifts with increasing body size. Those result supports the hypothesis that colouration in this species evolved under the competing pressures of natural and sexual selection to promote signals that are visible to conspecifics while being less perceptible to avian predators. Graphic abstrac

Old Age and Women’s Identity

Female identity is a dynamic concept, and it has been a very discussed issue by contemporary cultural critic. How does old age affect identity construction and perception in elderly woman? Has feminine gender an impact in subjective well-being? Psychological changes of midlife women have been as conflicting as the idea that society has about them. Personality changes after young adulthood in women is a controversial matter. Erikson proposed that women might not develop identities in early adulthood as men do. In fact, he argued that women develop them later, in the context of an intimate relationship. Moreover, identity development appears to have important consequences for midlife well-being. For example, Vandewater et al. found that women’s midlife well-being was facilitated by earlier attainment of a well-articulated identity. In these situations accomplishment of developmentally earlier tasks (identity formation) sets the stage for later psychological health. Our work sheds additional light on how women live this period of life in terms of happiness and purpose of life

Serum Resistin and Kidney Function: A Family-Based Study in Non-Diabetic, Untreated Individuals

Background: High serum resistin levels have been associated with kidney dysfunction. Most of these studies have been carried out in individuals with severe kidney impairment, diabetes, cardiovascular disease and related treatments. Thus, the observed association might have been influenced by these confounders. Our aim was to study the relationship between serum resistin, urinary albumin/creatinine ratio (ACR) and glomerular filtration rate (GFR) in a family-based sample, the Gargano Family Study (GFS) of 635 non diabetic, untreated Whites. Methods: A linear mixed effects model and bivariate analyses were used to evaluate the phenotypic and genetic relations between serum resistin and both ACR and eGFR. All analyses were adjusted for sex, age, age squared, BMI, systolic blood pressure, smoking habits and physical exercise. Results: After adjustments, resistin levels were slightly positively associated with ACR ($\beta \pm$SE = 0.049$\pm$0.023, p = 0.035) and inversely related to eGFR ($\beta \pm$SE = −1.43$\pm$0.61, p = 0.018) levels. These associations remained significant when either eGFR or ACR were, reciprocally, added as covariates. A genetic correlation (ρg = −0.31$\pm$0.12; adjusted p = 0.013) was observed between resistin and eGFR (but not ACR) levels. Conclusion: Serum resistin levels are independently associated with ACR and eGFR in untreated non-diabetic individuals. Serum resistin and eGFR share also some common genetic background. Our data strongly suggest that resistin plays a role in modulating kidney function

Serum Resistin, Cardiovascular Disease and All-Cause Mortality in Patients with Type 2 Diabetes

Background: High serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have been reported, so far, in type 2 diabetes. We studied the role of serum resistin on coronary artery disease, major cardiovascular events and all-cause mortality in type 2 diabetes. Methods: We tested the association of circulating resistin concentrations with coronary artery disease, major cardiovascular events (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and all-cause mortality in 2,313 diabetic patients of European ancestry from two cross-sectional and two prospective studies. In addition, the expression of resistin gene (RETN) was measured in blood cells of 68 diabetic patients and correlated with their serum resistin levels. Results: In a model comprising age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies, serum resistin was associated with coronary artery disease in both cross-sectional studies: OR (95%CI) per SD increment = 1.35 (1.10–1.64) and 1.99 (1.55–2.55). Additionally, serum resistin predicted incident major cardiovascular events (HR per SD increment = 1.31; 1.10–1.56) and all-cause mortality (HR per SD increment = 1.16; 1.06–1.26). Adjusting also for fibrinogen levels affected the association with coronary artery disease and incident cardiovascular events, but not that with all cause-mortality. Finally, serum resistin was positively correlated with RETN mRNA expression (rho = 0.343). Conclusions: This is the first study showing that high serum resistin (a likely consequence, at least partly, of increased RETN expression) is a risk factor for cardiovascular disease and all-cause mortality in diabetic patients of European ancestry

The ENPP1 Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals: Evidence for Interaction With Obesity in Diabetic Patients

Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals

GALNT2 Expression Is Reduced in Patients with Type 2 Diabetes: Possible Role of Hyperglycemia

Impaired insulin action plays a major role in the pathogenesis of type 2 diabetes, a chronic metabolic disorder which imposes a tremendous burden to morbidity and mortality worldwide. Unraveling the molecular mechanisms underlying insulin resistance would improve setting up preventive and treatment strategies of type 2 diabetes. Down-regulation of GALNT2, an UDPN-acetyl-alpha-D-galactosamine polypeptideN-acetylgalactosaminyltransferase-2 (ppGalNAc-T2), causes impaired insulin signaling and action in cultured human liver cells. In addition, GALNT2 mRNA levels are down-regulated in liver of spontaneously insulin resistant, diabetic Goto-Kakizaki rats. To investigate the role of GALNT2 in human hyperglycemia, we measured GALNT2 mRNA expression levels in peripheral whole blood cells of 84 non-obese and 46 obese non-diabetic individuals as well as of 98 obese patients with type 2 diabetes. We also measured GALNT2 mRNA expression in human U937 cells cultured under different glucose concentrations. In vivo studies indicated that GALNT2 mRNA levels were significantly reduced from non obese control to obese non diabetic and to obese diabetic individuals (p<0.001). In vitro studies showed that GALNT2 mRNA levels was reduced in U937 cells exposed to high glucose concentrations (i.e. 25 mmol/l glucose) as compared to cells exposed to low glucose concentration (i.e. 5.5 mmol/l glucose +19.5 mmol/l mannitol). In conclusion, our data indicate that GALNT2 is down-regulated in patients with type 2 diabetes and suggest that this association is, at least partly, secondary to hyperglycemia. Further studies are needed to understand whether GALNT2 down-regulation plays a pathogenic role in maintaining and/or aggravating the metabolic abnormalities of diabetic milieu. © 2013 Marucci et al

Neurocognitive Disorders and Dehydration in Older Patients: Clinical Experience Supports the Hydromolecular Hypothesis of Dementia

Abnormalities of water homeostasis can be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and neurodegenerative disease. The aim of this study was to analyze the serum osmolality of subjects with cognitive impairment. One thousand and ninety-one consecutive patients attending the Alzheimer&rsquo;s Evaluation Unit were evaluated with the Mini-Mental State Examination (MMSE), 21-Item Hamilton Depression Rating Scale (HDRS-21), Activities of Daily Living (ADL), Instrumental-ADL (IADL), Mini Nutritional Assessment (MNA), Exton-Smith Scale (ESS), and Cumulative Illness Rating Scale (CIRS). For each patient, the equation for serum osmolality developed by Khajuria and Krahn was applied. Five hundred and seventy-one patients had cognitive decline and/or depression mood (CD-DM) and 520 did not have CD-DM (control group). Patients with CD-DM were less likely to be male (p &lt; 0.001), and were more likely to be older (p &lt; 0.001), have a significant clear cognitive impairment (MMSE: p &lt; 0.001), show the presence of a depressive mood (HDRS-21: p &lt; 0.001) and have major impairments in ADL (p &lt; 0.001), IADL (p &lt; 0.001), MNA (p &lt; 0.001), and ESS (p &lt; 0.001), compared to the control group. CD-DM patients had a higher electrolyte concentration (Na+: p &lt; 0.001; K+: p &lt; 0.001; Cl&minus;: p &lt; 0.001), risk of dehydration (osmolality p &lt; 0.001), and kidney damage (eGFR: p = 0.021), than the control group. Alzheimer&rsquo;s disease (AD) patients showed a major risk for current dehydration (p &le; 0.001), and dehydration was associated with the risk of developing a type of dementia, like AD or vascular dementia (VaD) (OR = 2.016, p &lt; 0.001). In the multivariate analysis, the presence of dehydration state was associated with ADL (p &lt; 0.001) and IADL (p &lt; 0.001), but independently associated with age (r2 = 0.0046, p = 0.77), ESS (r2 = 0.0052, p = 0.54) and MNA (r2 = 0.0004, p = 0.48). Moreover, younger patients with dementia were significantly more dehydrated than patients without dementia (65&ndash;75 years, p = 0.001; 76&ndash;85 years, p = 0.001; &ge;86 years, p = 0.293). The hydromolecular hypothesis intends to explain the relationship between dehydration and cognitive impairment in older patients as the result of protein misfolding and aggregation, in the presence of a low interstitial fluid volume, which is a defect of the microcirculation. Defective proteins were shown to impair the amount of information in brain biomolecular mechanisms, with consequent neuronal and synaptic damage

GALNT2 expression is reduced in patients with Type 2 diabetes: possible role of hyperglycemia.

Impaired insulin action plays a major role in the pathogenesis of type 2 diabetes, a chronic metabolic disorder which imposes a tremendous burden to morbidity and mortality worldwide. Unraveling the molecular mechanisms underlying insulin resistance would improve setting up preventive and treatment strategies of type 2 diabetes. Down-regulation of GALNT2, an UDPN-acetyl-alpha-D-galactosamine polypeptideN-acetylgalactosaminyltransferase-2 (ppGalNAc-T2), causes impaired insulin signaling and action in cultured human liver cells. In addition, GALNT2 mRNA levels are down-regulated in liver of spontaneously insulin resistant, diabetic Goto-Kakizaki rats. To investigate the role of GALNT2 in human hyperglycemia, we measured GALNT2 mRNA expression levels in peripheral whole blood cells of 84 non-obese and 46 obese non-diabetic individuals as well as of 98 obese patients with type 2 diabetes. We also measured GALNT2 mRNA expression in human U937 cells cultured under different glucose concentrations. In vivo studies indicated that GALNT2 mRNA levels were significantly reduced from non obese control to obese non diabetic and to obese diabetic individuals (p<0.001). In vitro studies showed that GALNT2 mRNA levels was reduced in U937 cells exposed to high glucose concentrations (i.e. 25 mmol/l glucose) as compared to cells exposed to low glucose concentration (i.e. 5.5 mmol/l glucose +19.5 mmol/l mannitol). In conclusion, our data indicate that GALNT2 is down-regulated in patients with type 2 diabetes and suggest that this association is, at least partly, secondary to hyperglycemia. Further studies are needed to understand whether GALNT2 down-regulation plays a pathogenic role in maintaining and/or aggravating the metabolic abnormalities of diabetic milieu