Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction

Dysfunction of the exocrine pancreas is observed in diabetes, but links between concurrent exocrine and endocrine pancreatic disease and contributing genetic factors are poorly characterized. We studied two families with diabetes and exocrine pancreatic dysfunction by genetic, physiological and in vitro functional studies. A genome-wide screen in Family 1 linked diabetes to chromosome 9q34 (maximal lod score 5.07). Using fecal elastase deficiency as a marker of exocrine pancreatic dysfunction refined the critical chromosomal region to 1.16 Mb (maximal lod score 11.6). Here, we identified a single-base deletion in the variable number of tandem repeats (VNTR)-containing exon 11 of the carboxyl ester lipase (CEL) gene, a major component of pancreatic juice and responsible for the duodenal hydrolysis of cholesterol esters. Screening subjects with maturity-onset diabetes of the young identified Family 2, with another single-base deletion in CEL and a similar phenotype with beta-cell failure and pancreatic exocrine disease. The in vitro catalytic activities of wild-type and mutant CEL protein were comparable. The mutant enzyme was, however, less stable and secreted at a lower rate. Furthermore, we found some evidence for an association between common insertions in the CEL VNTR and exocrine dysfunction in a group of 182 unrelated subjects with diabetes (odds ratio 4.2 (1.6, 11.5)). Our findings link diabetes to the disrupted function of a lipase in the pancreatic acinar cells.     

Pineal indols and testosterone affect exploratory activity of male rats

The testosterone level has an inverse relation to activity in the open-field test. This is more important in red light than in white light. Pineal indols do not disturb this action. Some of these results are consistent with the assumption that androgens play a role on the exploratory activity of adult subjects.     

Reversed flow of Atlantic deep water during the Last Glacial Maximum

The meridional overturning circulation (MOC) of the Atlantic Ocean is considered to be one of the most important components of the climate system. This is because its warm surface currents, such as the Gulf Stream, redistribute huge amounts of energy from tropical to high latitudes and influence regional weather and climate patterns, whereas its lower limb ventilates the deep ocean and affects the storage of carbon in the abyss, away from the atmosphere. Despite its significance for future climate, the operation of the MOC under contrasting climates of the past remains controversial. Nutrient-based proxies and recent model simulations indicate that during the Last Glacial Maximum the convective activity in the North Atlantic Ocean was much weaker than at present. In contrast, rate-sensitive radiogenic (231)Pa/(230)Th isotope ratios from the North Atlantic have been interpreted to indicate only minor changes in MOC strength. Here we show that the basin-scale abyssal circulation of the Atlantic Ocean was probably reversed during the Last Glacial Maximum and was dominated by northward water flow from the Southern Ocean. These conclusions are based on new high-resolution data from the South Atlantic Ocean that establish the basin-scale north to south gradient in (231)Pa/(230)Th, and thus the direction of the deep ocean circulation. Our findings are consistent with nutrient-based proxies and argue that further analysis of (231)Pa/(230)Th outside the North Atlantic basin will enhance our understanding of past ocean circulation, provided that spatial gradients are carefully considered. This broader perspective suggests that the modern pattern of the Atlantic MOC-with a prominent southerly flow of deep waters originating in the North Atlantic-arose only during the Holocene epoch.     

Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders

SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders.     

Pineal indols and testosterone affect exploratory activity of male rats

Summary The testosterone level has an inverse relation to activity in the open-field test. This is more important in red light than in white light. Pineal indols do not disturb this action. Some of these results are consistent with the assumption that androgens play a role on the exploratory activity of adult subjects.     

Effects of constant light exposure and blindness on the oxidative metabolism of selected brain areas in male rats

Summary Male rats were housed in continous illumination or blinded when 21 day-old and killed 69 days later. The continuous illumination exposure increased the weights of testes and sex accessory organs and reduced the pineal gland weight. Blindness decreased weights of testes, sex accessory organs and anterior pituitary. The oxygen consumption rate of the hypothalamus was higher in the blinded animals than in the controls and lower in the continuously illuminated rats. No one of such groups showed significant changes in the oxygen consumption by either the amygdata or the hippocampus.