Loss of ZnT8 function protects against diabetes by enhanced insulin secretion.

A rare loss-of-function allele p.Arg138* in SLC30A8 encoding the zinc transporter 8 (ZnT8), which is enriched in Western Finland, protects against type 2 diabetes (T2D). We recruited relatives of the identified carriers and showed that protection was associated with better insulin secretion due to enhanced glucose responsiveness and proinsulin conversion, particularly when compared with individuals matched for the genotype of a common T2D-risk allele in SLC30A8, p.Arg325. In genome-edited human induced pluripotent stem cell (iPSC)-derived β-like cells, we establish that the p.Arg138* allele results in reduced SLC30A8 expression due to haploinsufficiency. In human β cells, loss of SLC30A8 leads to increased glucose responsiveness and reduced KATP channel function similar to isolated islets from carriers of the T2D-protective allele p.Trp325. These data position ZnT8 as an appealing target for treatment aimed at maintaining insulin secretion capacity in T2D

Heavy genealogy: mapping the currents, contraflows and conflicts of the emergent field of metal studies, 1978-2010

What is metal studies? How can we define and characterize it? How has it emerged as a body of academic enquiry? What are its dominant disciplinary strands, theoretical concepts and preferred methodologies? Which studies have claimed most attention, defined the goals of scholarship, typical research strategies and values? How has the claim for the legitimacy or symbolic value of metal scholarship been achieved (if it has): over time and through gradual acceptance or through conflict and contestation? How can this process of formation, or strategy of legitimation, be mapped, examined and interrogated and which methods of historical, institutional and cultural analysis are best suited to this task? Working with the most complete bibliography to date of published research on heavy metal, music and culture (the MSBD), this article employs Foucault’s archaeological “method” to examine the institutional, cultural and political contexts and conflicts that inform the genealogy of this scholarship. Such analysis reveals a formative, largely negative account of heavy metal to be found in the “sociology of rock”; a large volume of psychology work, examining heavy metal music preference as an indicator of youth risk, deviance and delinquency; sociological work on youth and deviancy critical of the values of this research and its links to social policy and politics; culminating in the work of Weinstein and Walser, who advocate a perspective sympathetic to the values of heavy metal fans themselves. Following Bourdieu, I interpret such symbolic strategies as claims for expertise within the academic field that are high or low in symbolic capital to the extent they can attain disciplinary autonomy. I then go on to examine the most recent strands of research, within cultural studies and ethnomusicology, concerned with the global metal music diaspora, and consider to what extent such work is constitutive of a coherent subfield of metal studies that can be distinguished from earlier work and what the implications of this might be

Heritability and familiality of type 2 diabetes and related quantitative traits in the Botnia Study.

AIMS/HYPOTHESIS: To study the heritability and familiality of type 2 diabetes and related quantitative traits in families from the Botnia Study in Finland. METHODS: Heritability estimates for type 2 diabetes adjusted for sex, age and BMI are provided for different age groups of type 2 diabetes and for 34 clinical and metabolic traits in 5,810 individuals from 942 families using a variance component model (SOLAR). In addition, family means of these traits and their distribution across families are calculated. RESULTS: The strongest heritability for type 2 diabetes was seen in patients with age at onset 35-60 years (h (2) = 0.69). However, including patients with onset up to 75 years dropped the h (2) estimates to 0.31. Among quantitative traits, the highest h (2) estimates in all individuals and in non-diabetic individuals were seen for lean body mass (h (2) = 0.53-0.65), HDL-cholesterol (0.52-0.61) and suppression of NEFA during OGTT (0.63-0.76) followed by measures of insulin secretion (insulinogenic index [IG(30)] = 0.41-0.50) and insulin action (insulin sensitivity index [ISI] = 0.37-0.40). In contrast, physical activity showed rather low heritability (0.16-0.18), whereas smoking showed strong heritability (0.57-0.59). Family means of these traits differed two- to fivefold between families belonging to the lowest and highest quartile of the trait (p < 0.00001). CONCLUSIONS/INTERPRETATION: To detect stronger genetic effects in type 2 diabetes, it seems reasonable to restrict inclusion of patients to those with age at onset 35-60 years. Sequencing of families with extreme quantitative traits could be an important next step in the dissection of the genetics of type 2 diabetes