Effects of simulated microgravity on the development and maturation of dissociated cortical neurons

Although a wealth of evidence supports the hypothesis that some functions of the nervous system may be altered during exposure to microgravity, the possible changes in basic neuronal physiology are not easy to assess. Indeed, few studies have examined whether microgravity affects the development of neurons in culture. In the present study, a suspension of dissociated cortical cells from rat embryos were exposed to 24 h of simulated microgravity before plating in a normal adherent culture system. Both preexposed and control cells were used after a period of 7-10 d in vitro. The vitality and the level of reactive oxygen species of cultures previously exposed did not differ from those of normal cultures. Cellular characterization by immunostaining with a specific antibody displayed normal neuronal phenotype in control cells, whereas pretreatment in simulated microgravity revealed an increase of glial fibrillary acidic protein fluorescence in the elongated stellate glial cells. Electrophysiological recording indicated that the electrical properties of neurons preexposed were comparable with those of controls. Overall, our results indicate that a short time of simulated microgravity preexposure does not affect dramatically the ability of dissociated neural cells to develop and differentiate in an adherent culture system.     

Drought stress increased survival and development of emerald ash borer larvae on coevolved Manchurian ash and implicates phloem‐based traits in resistance

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Pimarane diterpenes: Natural source,stereochemical configuration,and biological activity

Plants and fungi are seemingly inexhaustible sources of interesting natural products with remarkable structural and biological diversity. One of the most important groups is the terpenes, ubiquitous natural products that are generated by 2 now well‐established biosynthetic pathways: the older mevalonate and the more recently discovered 1‐deoxyxylulose‐5‐phosphate. Among the diterpenes, the pimarane diterpenes are a very representative subgroup with several and interesting biological activities resulting from different functional group modifications. In this review, we outline the method of their structure determination, mainly spectroscopic results, their absolute configuration, and structure‐activity relationships, were reported, as well as the mode of action for selected examples from plants, marine organisms, and fungi. The pimarane, isopimarane, and ent‐pimarane diterpenes covered in this review have a wide range of biological activities including antimicrobial, antifungal, antiviral, phytotoxic, phytoalexin, cytotoxicity, and antispasmodic and relaxant effects.     

Coinhibitory molecules in cancer biology and therapy

The adaptive immune response is controlled by checkpoints represented by coinhibitory molecules, which are crucial for maintaining self-tolerance and minimizing collateral tissue damage under physiological conditions. A growing body of preclinical evidence supports the hypothesis that unleashing this immunological break might be therapeutically beneficial in the fight against cancer, as it would elicit an effective antitumor immune response. Remarkably, recent clinical trials have demonstrated that this novel strategy can be highly effective in the treatment of patients with cancer, as shown by the paradigmatic case of ipilimumab (a monoclonal antibody blocking the coinhibitory molecule cytotoxic T lymphocyte associated antigen-4 [CTLA4]) that is opening a new era in the therapeutic approach to a chemoresistant tumor such as cutaneous melanoma. In this review we summarize the biology of coinhibitory molecules, overview the experimental and clinical attempts to interfere with these immune checkpoints to treat cancer and critically discuss the challenges posed by such a promising antitumor modality.     

The effects of stress induced by cortisol administration on the repeatability of swimming performance tests in the European sea bass (Dicentrarchus labrax L.)

The impact of stress induced by cortisol administration on the swimming performance of the European sea bass was tested measuring the fish recovery capability using a respirometer. The recovery test consisted of two exhaustive swimming exercises (U _crit) separated by a recovery period. Thirty-eight fish were subjected to this trial preceded or not (control group) by a cortisol (cortisol group) or saline (placebo) injection. For validation, the classical stress parameters (cortisol, glucose, lysozyme, Hct, Hb and RBCC) were monitored. During the recovery tests, only the cortisol group showed a significant reduction in the recovery capability that was interpreted as a sign of possible physiological impairment. Hct, Hb and RBCC did not show significant inter and intra-group differences, while cortisol and glucose increased as a response to fatigue in all the groups at the end of the trials. No immune (lysozyme) response was observed in control and placebo groups, while a reduction was evidenced in the cortisol group.     

Glycoform-Selective Prion Formation in Sporadic and Familial Forms of Prion Disease

The four glycoforms of the cellular prion protein (PrP^C) variably glycosylated at the two N-linked glycosylation sites are converted into their pathological forms (PrP^Sc) in most cases of sporadic prion diseases. However, a prominent molecular characteristic of PrP^Sc in the recently identified variably protease-sensitive prionopathy (VPSPr) is the absence of a diglycosylated form, also notable in familial Creutzfeldt-Jakob disease (fCJD), which is linked to mutations in PrP either from Val to Ile at residue 180 (fCJD^V180I) or from Thr to Ala at residue 183 (fCJD^T183A). Here we report that fCJD^V180I, but not fCJD^T183A, exhibits a proteinase K (PK)-resistant PrP (PrP^res) that is markedly similar to that observed in VPSPr, which exhibits a five-step ladder-like electrophoretic profile, a molecular hallmark of VPSPr. Remarkably, the absence of the diglycosylated PrP^res species in both fCJD^V180I and VPSPr is likewise attributable to the absence of PrP^res glycosylated at the first N-linked glycosylation site at residue 181, as in fCJD^T183A. In contrast to fCJD^T183A, both VPSPr and fCJD^V180I exhibit glycosylation at residue 181 on di- and monoglycosylated (mono181) PrP prior to PK-treatment. Furthermore, PrP^V180I with a typical glycoform profile from cultured cells generates detectable PrP^res that also contains the diglycosylated PrP in addition to mono- and unglycosylated forms upon PK-treatment. Taken together, our current in vivo and in vitro studies indicate that sporadic VPSPr and familial CJD^V180I share a unique glycoform-selective prion formation pathway in which the conversion of diglycosylated and mono181 PrP^C to PrP^Sc is inhibited, probably by a dominant-negative effect, or by other co-factors.