Diabetes mellitus in people with schizophrenia,bipolar disorder and major depressive disorder: a systematic review and large scale meta‐analysis

Type 2 diabetes mellitus (T2DM) is highly predictive of cardiovascular diseases and can have particularly deleterious health impacts in people with severe mental illness (SMI), i.e. schizophrenia, bipolar disorder or major depressive disorder. This meta‐analysis aimed: a) to describe pooled frequencies of T2DM in people with SMI; b) to analyze the influence of demographic, illness and treatment variables as well as T2DM assessment methods; and c) to describe T2DM prevalence in studies directly comparing persons with each specific SMI diagnosis to general population samples. The trim and fill adjusted pooled T2DM prevalence among 438,245 people with SMI was 11.3% (95% CI: 10.0%‐12.6%). In antipsychotic‐naïve participants, the prevalence of T2DM was 2.9% (95% CI: 1.7%‐4.8%). There were no significant diagnostic subgroup differences. A comparative meta‐analysis established that multi‐episode persons with SMI (N=133,470) were significantly more likely to have T2DM than matched controls (N=5,622,664): relative risk, RR=1.85, 95% CI: 1.45‐2.37, p<0.001. The T2DM prevalence was consistently elevated in each of the three major diagnostic subgroups compared to matched controls. Higher T2DM prevalences were observed in women with SMI compared to men (RR=1.43, 95% CI: 1.20‐1.69, p<0.001). Multi‐episode (versus first‐episode) status was the only significant predictor for T2DM in a multivariable meta‐regression analysis (r²=0.52, p<0.001). The T2DM prevalence was higher in patients prescribed antipsychotics, except for aripriprazole and amisulpride. Routine screening and multidisciplinary management of T2DM is needed. T2DM risks of individual antipsychotic medications should be considered when making treatment choices.     

Solar Radiation Induces Non-Nuclear Perturbations and a False Start to Regulated Exocytosis in Cryptosporidium parvum

Stratospheric ozone depletion, climate warming and acidification of aquatic ecosystems have resulted in elevated levels of solar radiation reaching many aquatic environments with an increased deleterious impact on a wide range of living organisms. While detrimental effects on living organisms are thought to occur primarily through DNA damage, solar UV can also damage cellular proteins, lipids and signalling pathways. Cryptosporidium, a member of the eukaryotic phylum Apicomplexa, contain numerous vesicular secretory organelles and their discharge via regulated exocytosis is essential for the successful establishment of infection. Using flow cytometric techniques we demonstrate that solar UV rapidly induces sporozoite exocytosis resulting in a significant reduction in the ability of sporozoites to attach and invade host cells. We found that solar UV induced sporozoite membrane depolarization, resulting in reduced cellular ATP and increased cytosolic calcium. These changes were accompanied by a reduction in the internal granularity of sporozoites, indicative of apical organelle discharge, which was confirmed by analysis of sporozoites with an exocytosis-sensitive dye. The precise timing of apical organelle discharge in the presence of a compatible host cell is critical for sporozoite attachment and invasion. Our results demonstrate for the first time how solar UV radiation can interfere with exocytosis, a fundamental cellular process in all eukaryotic cells. We contend that not only may the forecast increases in solar radiation in both aquatic and terrestrial environments significantly affect members of the Apicomplexa, solar UV-induced membrane depolarizations resulting in cytosolic calcium perturbation may affect a wider range of eukaryotic organisms through antagonistic effects on a myriad of calcium dependant cellular functions.     

Role of transmembrane segment 10 in efflux mediated by the staphylococcal multidrug transport protein QacA

The staphylococcal multidrug exporter QacA confers resistance to a wide range of structurally dissimilar monovalent and bivalent cationic antimicrobial compounds. To understand the functional importance of transmembrane segment 10, which is thought to be involved in substrate binding, cysteine-scanning mutagenesis was performed in which 35 amino acid residues in the putative transmembrane helix and its flanking regions were replaced in turn with cysteine. Solvent accessibility analysis of the introduced cysteine residues using fluorescein maleimide indicated that transmembrane segment 10 of QacA contains a 20-amino-acid hydrophobic core and may extend from Pro-309 to Ala-334. Phenotypic analysis and fluorimetric transport assays of these mutants showed that Gly-313 is important for the efflux of both monovalent and bivalent cationic substrates, whereas Asp-323 is only important for the efflux of bivalent substrates and probably forms part of the bivalent substrate-binding site(s) together with Met-319. Furthermore, the effects of N-ethyl-maleimide treatment on ethidium and 4',6-diamidino-2-phenylindole export mediated by the QacA mutants suggest that the face of transmembrane segment 10 that contains Asp-323 may also be close to the monovalent substrate-binding site(s), making this helix an integral component of the QacA multidrug-binding pocket.     

Dispersal of newly eclosed European corn borer adults (Lepidoptera: Crambidae) from corn into small-grain aggregation plots

Genetically modified, insecticidal Bacillus thuringiensis (Bt) corn, Zea mays L., hybrids are used throughout the Corn Belt for European corn borer, Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae), control. To slow development of Bt corn resistance, the Environmental Protection Agency requires growers to plant a refuge. Determining the appropriate distance between a refuge and Bt corn, and development of mitigation-remediation strategies such as mass releases of susceptible moths, requires an understanding of adult dispersal and mating behavior. However, much remains unknown about these behaviors. Because mating often occurs in grass near cornfields where adult O. nubilalis aggregate, we planted small-grain plots as aggregation sites in an attempt to retain mass-released adults. The objectives of this study were to examine influences of pheromone lure, plant density, and plant species on distributions of feral and newly emerged, laboratory-reared O. nubilalis among small-grain aggregation plots. Feral adults were collected in aggregation plots in relative abundance, indicating that small-grain plots were acceptable aggregation sites. In contrast, newly emerged adults that were released weekly as dye-marked pupae were rarely found in aggregation plots, with approximately 150-1,500-fold fewer adults captured than expected if all released adults had occupied the plots for > or = 1 d. The majority of newly emerged adults did not colonize the aggregation plots, suggesting that recently eclosed adults leave their natal field and do not colonize the first aggregation sites encountered. Plant species significantly influenced adult distributions among aggregation plots. Mass releases of laboratory-reared pupae in the field may not be a viable remediation tactic because almost all of the newly emerged adults dispersed beyond 300 m of the release point.     

Spike Inference from Calcium Imaging Using Sequential Monte Carlo Methods

As recent advances in calcium sensing technologies facilitate simultaneously imaging action potentials in neuronal populations, complementary analytical tools must also be developed to maximize the utility of this experimental paradigm. Although the observations here are fluorescence movies, the signals of interest—spike trains and/or time varying intracellular calcium concentrations—are hidden. Inferring these hidden signals is often problematic due to noise, nonlinearities, slow imaging rate, and unknown biophysical parameters. We overcome these difficulties by developing sequential Monte Carlo methods (particle filters) based on biophysical models of spiking, calcium dynamics, and fluorescence. We show that even in simple cases, the particle filters outperform the optimal linear (i.e., Wiener) filter, both by obtaining better estimates and by providing error bars. We then relax a number of our model assumptions to incorporate nonlinear saturation of the fluorescence signal, as well external stimulus and spike history dependence (e.g., refractoriness) of the spike trains. Using both simulations and in vitro fluorescence observations, we demonstrate temporal superresolution by inferring when within a frame each spike occurs. Furthermore, the model parameters may be estimated using expectation maximization with only a very limited amount of data (e.g., ∼5-10 s or 5-40 spikes), without the requirement of any simultaneous electrophysiology or imaging experiments.     

Optimized Expression of Full-Length IgG1 Antibody in a Common E. coli Strain

Multi-polypeptide proteins such as antibodies are difficult to express in prokaryotic systems such as E. coli due to the complexity of protein folding plus secretion. Thus far, proprietary strains or fermenter cultures have been required for appreciable yields. Previous studies have shown that expression of heterologous proteins in E. coli can be enhanced by the reduction of protein translation rates. In this paper, we demonstrate that useful quantities of full-length IgG can be expressed and purified from the common E. coli laboratory strain HB2151 in standard shaking culture using a simple strategy of reduced inducer concentration combined with delayed induction times to modulate translation rates. Purified IgG had only marginally reduced avidity compared to mammalian derived IgG. This indicates that this technique can be used to derive antibodies of potentially equal utility as those expressed in mammalian cell culture, particularly for applications where effector functions mediated by the glycosylated residues in the Fragment Crystallizable (Fc) portion of the immunoglobulin are not required.     

Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone

Bone isremoved or replaced in defined locations by targeting osteoclasts andosteoblasts in response to its local history of mechanical loading.There is increasing evidence that osteocytes modulate this targeting bytheir apoptosis, which is associated with locally increasedbone resorption. To investigate the role of osteocytes in the controlof loading-related modeling or remodeling, we studied the effects onosteocyte viability of short periods of mechanical loading applied tothe ulnae of rats. Loading, which produced peak compressive strains of0.003 or 0.004, was associated with a 78% reduction in theresorption surface at the midshaft. The same loading regimen resultedin a 40% relative reduction in osteocyte apoptosis at the samesite 3 days after loading compared with the contralateral side(P = 0.01). The proportion of osteocytes that wereapoptotic was inversely related to the estimated local strain(P < 0.02). In contrast, a single short period ofloading resulting in strains of 0.008 engendered both tissuemicrodamage and subsequent bone remodeling and was associated with aneightfold increase in the proportion of apoptotic osteocytes(P = 0.02) at 7 days. This increase in osteocyteapoptosis was transient and preceded both intracorticalremodeling and death of half of the osteocytes (P < 0.01). The data suggest that osteocytes might use their U-shapedsurvival response to strain as a mechanism to influence boneremodeling. We hypothesize that this relationship reflects a causalmechanism by which osteocyte apoptosis regulates bone'sstructural architecture.

     

Permian parallelisms: Reanalysis of †Tshekardocoleidae sheds light on the earliest evolution of the Coleoptera

The Coleoptera provides an excellent example of the value of fossils for understanding the evolutionary patterns of recent lineages. We reevaluate the morphology of the Early Permian †Tshekardocoleidae to test alternative phylogenetic hypotheses relating to the Palaeozoic evolution of the order. We discuss prior interpretations and revise an earlier data matrix. Both Bayesian and parsimony analyses support the monophyly of Coleoptera excluding †Tshekardocoleidae (= Mesocoleoptera), and of Coleoptera excluding †Tshekardocoleidae and †Permocupedidae (= Metacoleoptera). Plesiomorphies preserved in †Tshekardocoleidae are elytra, which rest over the body in a loose tent-like manner, with flat lateral flanges, projecting beyond the abdominal apex, and abdomens that are flexible and nearly cylindrical. Apomorphies of Mesocoleoptera include shortening of the elytra and a closer fit with the flattened and probably more rigid abdomen. A crucial synapomorphy of Metacoleoptera is the tightly sealed subelytral space, which may have been advantageous during the Permian aridification. Taxon exclusion experiments show that †Tshekardocoleidae is crucial for understanding the early evolution of Coleoptera and that its omission strongly affects ancestral state polarities as well as topology, including crown-group taxa. By constraining the relationships of extant taxa to match those supported by phylogenomic analysis, we demonstrate that features shared by Archostemata with Permian stem groups are most reasonably supported as plesiomorphic and that the smooth and simplified body forms of Polyphaga, Adephaga, Myxophaga, and Micromalthidae were derived in parallel. Our study highlights the reciprocal illumination of molecular, morphological, and paleontological data, and paves the way for tip-dating analysis across the order.     

Evaluation of intramolecular equilibria in complexes formed between substituted imidazole ligands and nickel (II), copper (II) or zinc (II)

The metal ion-binding properties of imidazole-4-acetate (ImA-), 4(5)-aminoimidazole-5(4)-carboxamide (AImC), 2,2'biimidazole(BiIm) (I. T?r?k et al., J. Inorg. Biochem. 71 (1998) 7-14), and bis (imidazol-2-yl)methane(BiImM) (K. Várnagy et al., J. Chem. Soc., Dalton Trans. (1994) 2939-2945) have been evaluated by using the recently published stability constants and by applying the recently established log K(ML)M versus pK(HL)H straight-line plots (L. E. Kapinos et al., Inorg. Chim. Acta 280 (1998) 50-56) which hold for simple imidazole-type ligands. The indicated analysis regarding the intramolecular equilibrium between a monodentatally imidazole-nitrogen-coordinated (open) species and a chelated isomer provides helpful insights, e.g., the formation degree of chelates is more favored if six-membered rings can be formed, as in the case with M(BiImM)2+ compared to M(BiIm)2+, though in both instances the formation degree of the chelates is large. The formation degree of chelates in the M(ImA)+ complexes increases in the series Zn(ImA)+ (87%)相似文献