Control by Ca2+ of mitochondrial structure and function in pancreatic β-cells

Mitochondria play a central role in glucose metabolism and the stimulation of insulin secretion from pancreatic β-cells. In this review, we discuss firstly the regulation and roles of mitochondrial Ca2+ transport in glucose-regulated insulin secretion, and the molecular machinery involved. Next, we discuss the evidence that mitochondrial dysfunction in β-cells is associated with type 2 diabetes, from a genetic, functional and structural point of view, and then the possibility that these changes may in part be mediated by dysregulation of cytosolic Ca2+. Finally, we review the importance of preserved mitochondrial structure and dynamics for mitochondrial gene expression and their possible relevance to the pathogenesis of type 2 diabetes

Distribution, Abundance, and Age Structure of a Population of the Burrowing Mayfly, Hexagenia Limbata, in an Ohio Pond

Author Institution: Department of Zoology, Miami UniversityRUTTER, ROBERT P., AND THOMAS E. WISSING, Distribution, Abundance and Age Structure of a Population of the Burrowing Mayfly, Hexagenia limbata, in an Ohio Pond. Ohio J. Sci. 75(1): 7, 1975

Olanzapine Attenuates Cue-elicited Craving for Tobacco

Rationale: Recent biological conceptualizations of craving and addiction have implicated mesolimbic dopamine activity as a central feature of the process of addiction. Imaging, and pharmacological studies have supported a role for dopaminergic structures in cue-elicited craving for tobacco. Objective: If mesolimbic dopamine activity is associated with cue-elicited craving for tobacco, a dopamine antagonist should attenuate cueelicited craving for tobacco. Thus, the aim of the present study was to determine whether an atypical antipsychotic (olanzapine, 5 mg) decreased cue-elicited craving for tobacco. Method: Participants were randomly assigned to 5 days of pretreatment with olanzapine (5 mg; n=31) or were randomly assigned to 5 days of a matching placebo (n=28). Approximately 8 h after the last dose, participants were exposed to a control cue (pencil) followed by exposure to smoking cues. Participants subsequently smoked either nicotine cigarettes or de-nicotinized cigarettes. Results: Olanzapine attenuated cue-elicited craving for tobacco but did not moderate the subjective effects of smoking. Discussion: This study represents one of the first investigations of the effect of atypical antipsychotics on cue-elicited craving for tobacco. The results suggest that medications with similar profiles may reduce cue-elicited craving, which in turn, may partially explain recent observations that atypical antipsychotics may reduce substance use

The Effect of Olanzapine on Craving and Alcohol Consumption

Previous studies have indicated that olanzapine decreases craving after a priming dose of alcohol, that craving after a priming dose of alcohol is greater among individuals with the seven-repeat allele of the DRD4 variable number of tandem repeats (VNTR) polymorphism, and that the effect of olanzapine (a D2/D4 antagonist) is more pronounced among individuals with this allele. The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving and differentially effective as a treatment for alcohol dependence over the course of a 12-week, randomized, placebo-controlled trial among individuals with and without the seven-repeat allele. Participants who met DSM IV criteria for alcohol dependence were randomly assigned to receive olanzapine (5 mg) or a placebo over the course of the trial. After 2 weeks of treatment, participants completed a cue reactivity assessment. The results suggested that participants who were homozygous or heterozygous for the seven (or longer)-repeat allele of the DRD4 VNTR responded to olanzapine with reductions in cue-elicited craving as well as reductions in alcohol consumption over the course of the 12-week trial, whereas individuals with the shorter alleles did not respond favorably to olanzapine

Human alpha cell transcriptomic signatures of types 1 and 2 diabetes highlight disease-specific dysfunction pathways

Although glucagon secretion is perturbed in both T1D and T2D, the pathophysiological changes in individual pancreatic alpha cells are still obscure. Using recently curated single-cell RNASeq data from T1D or T2D donors and their controls, we identified alpha cell transcriptomic alterations consistent with both common and discrete pathways. Although alterations in alpha cell identity gene (ARX, MAFB) expression were conserved, cytokine-regulated genes and genes involved in glucagon biosynthesis and processing were up-regulated in T1D. Conversely, mitochondrial genes associated with ROS (COX7B, NQO2) were dysregulated in T2D. Additionally, T1D alpha cells displayed altered expression of autoimmune-induced ER stress genes (ERLEC1, HSP90), whilst those from T2D subjects showed modified glycolytic and citrate cycle gene (LDHA?, PDHB, PDK4) expression. Thus, despite conserved alterations related to loss of function, alpha cells display disease-specific gene signatures which may be secondary to the main pathogenic events in each disease, namely immune- or metabolism-mediated-stress, in T1D and T2D, respectively

Water Availability and Deformation Processes in Smectite-Rich Gouges During Seismic Slip

Smectite clays occur in subduction zone fault cores at shallow depth (approximately 1 km; e.g., Japan Trench) and landslide d\ue9collements (e.g., Vajont, Italy, 1963). The availability of pore fluids affects the likelihood that seismic slip propagates from deeper to shallow fault depths or that a landslide accelerates to its final collapse. To investigate the deformation processes active during seismic faulting we performed friction experiments with a rotary machine on 2-mm-thick smectite-rich gouge layers (70/30 wt % Ca-montmorillonite/opal) sheared at 5-MPa normal stress, at slip rates of 0.001, 0.01, 0.1, and 1.3 m/s, and total displacement of 3 m. Experiments were performed on predried gouges under vacuum, under room humidity and under partly saturated conditions. The fault shear strength measured in the experiments was included in a one-dimensional numerical model incorporating frictional heating, thermal, and thermochemical pressurization. Quantitative X-ray powder diffraction and scanning electron microscopy investigations were performed on pristine and deformed smectite-rich gouges. Under dry conditions, cataclasis and amorphization dominated at slip rates of 0.001\u20130.1 m/s, whereas grain size sensitive flow and, under vacuum, frictional melting occurred at fast slip rates (1.3 m/s). Under partly saturated conditions, frictional slip in a smectite foliation occurred in combination with pressurization of water by shear-enhanced compaction and, for V = 0.01\u20131.3 m/s, with thermal pressurization. Pseudotachylytes, the only reliable microstructural markers for seismic slip, formed only with large frictional power (>2 MW/m2), which could be achieved at shallow depth with high slip rates, or, at depth, with high shear stress in dehydrated smectites