Association between Antibodies to the MR 67,000 Isoform of Glutamate Decarboxylase (GAD) and Type 1 (Insulin-Dependent) Diabetes Mellitus with Coexisting Autoimmune Polyendocrine Syndrome Type II

By using an immunoprecipitation assay, we analysed reactivity of autoantibodies to human recombinant GAD65 and GAD67 in sera from patients with autoimmune polyendocrine syndrome Type II (APS II) with and without Type 1 (insulin-dependent) diabetes mellitus (IDDM) compared to patients with organ-specific autoimmunity. Overall antibodies to GAD65 were correlated with IDDM in all study groups, whereas GAD67 antibodies were associated with IDDM when APS II coexists. Antibodies to GAD65 and GAD67 were detected in 13 (44.8%) and 7 (24.1%) out of 29 APS II patients with IDDM, but in only 4 (13.8%) and 2 (6.9%) out of 29 APS II patients without IDDM, respectively (p < 0.05). In short-standing IDDM (< 1 year), antibodies to GAD67 were significantly more frequent in patients with APS II (5 of 9 [55.6%] subjects) compared to matched diabetic patients without coexisting polyendocrinopathy (1 of 18 [5.6%] subjects) (p < 0.02). The levels of GAD65 (142 ± 90 AU) and GAD67 antibodies (178 ± 95 AU) were significantly higher in patients with polyglandular disease than in patients with isolated IDDM (91 ± 85 AU and 93 ± 57 AU) (p < 0.02). Interestingly, all 11 GAD67 antibody positive subjects also had GAD65 antibodies (p < 0.0001), and in 10 of 11 anti-GAD67 positive sera the GAD67 antibodies could be blocked by either GAD67 or GAD65, suggesting the presence of cross-reactive autoantibodies. No correlation was observed between GAD antibodies and age, sex or any particular associated autoimmune disease, besides IDDM. GAD antibodies were present in only 1 of 6 (16.7%) patients with APS Type I, in 1 of 26 (3.9%) patients with autoimmune thyroid disease but in none of the patients with Addison's disease (n = 16), pernicious anaemia (n = 7) or normal controls (n = 50). Our data suggest distinct antibody specificities reactive to GAD isoforms in APS II and IDDM, which might reflect different mechanisms of autoimmune response in IDDM with coexisting autoimmune polyendocrine autoimmunity

Climate and land-use changes affecting river sediment and brown trout in alpine countries--a review

BACKGROUND, AIM, AND SCOPE: Catch decline of freshwater fish has been recorded in several countries. Among the possible causes, habitat change is discussed. This article focuses on potentially increased levels of fine sediments going to rivers and their effects on gravel-spawning brown trout. Indications of increased erosion rates are evident from land-use change in agriculture, changes in forest management practices, and from climate change. The latter induces an increase in air and river water temperatures, reduction in permafrost, changes in snow dynamics and an increase in heavy rain events. As a result, an increase in river sediment is likely. Suspended sediment may affect fish health and behaviour directly. Furthermore, sediment loads may clog gravel beds impeding fish such as brown trout from spawning and reducing recruitment rates. To assess the potential impact on fine sediments, knowledge of brown trout reproductive needs and the effects of sediment on brown trout health were evaluated. APPROACH: We critically reviewed the literature and included results from ongoing studies to answer the following questions, focusing on recent decades and rivers in alpine countries. Have climate change and land-use change increased erosion and sediment loads in rivers? Do we have indications of an increase in riverbed clogging? Are there indications of direct or indirect effects on brown trout from increased suspended sediment concentrations in rivers or from an increase in riverbed clogging? RESULTS: Rising air temperatures have led to more intensive precipitation in winter months, earlier snow melt in spring, and rising snow lines and hence to increased erosion. Intensification of land use has supported erosion in lowland and pre-alpine areas in the second half of the twentieth century. In the Alps, however, reforestation of abandoned land at high altitudes might reduce the erosion risk while intensification on the lower, more easily accessible slopes increases erosion risk. Data from laboratory experiments show that suspended sediments affect the health and behaviour of fish when available in high amounts. Point measurements in large rivers indicate no common lethal threat and suspended sediment is rarely measured continuously in small rivers. However, effects on fish can be expected under environmentally relevant conditions. River bed clogging impairs the reproductive performance of gravel-spawning fish. Discussion: Overall, higher erosion and increased levels of fine sediment going into rivers are expected in future. Additionally, sediment loads in rivers are suspected to have considerably impaired gravel bed structure and brown trout spawning is impeded. Timing of discharge is put forward and is now more likely to affect brown trout spawning than in previous decades. Conclusions: Reports on riverbed clogging from changes in erosion and fine sediment deposition patterns, caused by climate change and land-use change are rare. This review identifies both a risk of increases in climate erosive forces and fine sediment loads in rivers of alpine countries. Increased river discharge and sediment loads in winter and early spring could be especially harmful for brown trout reproduction and development of young life stages. Recently published studies indicate a decline in trout reproduction from riverbed clogging in many rivers in lowlands and alpine regions. However, the multitude of factors in natural complex ecosystems makes it difficult to address a single causative factor. Recommendations and perspectives: Further investigations into the consequences of climate change and land-use change on river systems are needed. Small rivers, of high importance for the recruitment of gravel-spawning fish, are often neglected. Studies on river bed clogging are rare and the few existing studies are not comparable. Thus, there is a strong need for the development of methods to assess sediment input and river bed clogging. As well, studies on the effects to fish from suspended sediments and consequences of gravel beds clogging under natural conditions are urgently needed

An Introduction to Synthetic Biology

Synthetic biology is a newly emerged discipline that came into light several years ago. It is an interdisciplinary field bringing together the expertise from science, engineering, and computing to create artificial parts or systems in the biological world. This chapter provides a concise overview of the background and developments in synthetic biology with focus on some of the latest research findings. It is believed that synthetic biology can open new doors for solutions to many existing daily life problems. However, there are still many challenges to be overcome due to the complex nature of biological systems. The discoveries and knowledge that will be gained from the ongoing studies in synthetic biology will enrich our understanding towards how life has been designed by nature and to what extent it can be altered or improved by artificial interference