Alien Registration- Howlett, Edna E. (Augusta, Kennebec County)

https://digitalmaine.com/alien_docs/17340/thumbnail.jp

Age and Ovariectomy Abolish Beneficial Effects of Female Sex on Rat Ventricular Myocytes Exposed to Simulated Ischemia and Reperfusion

Sex differences in responses to myocardial ischemia have been described, but whether cardiomyocyte function is influenced by sex in the setting of ischemia and reperfusion has not been elucidated. This study compared contractions and intracellular Ca2+ in isolated ventricular myocytes exposed to ischemia and reperfusion. Cells were isolated from anesthetized 3-month-old male and female Fischer 344 rats, paced at 4 Hz (37°C), exposed to simulated ischemia (20 mins) and reperfused. Cell shortening (edge detector) and intracellular Ca2+ (fura-2) were measured simultaneously. Cell viability was assessed with Trypan blue. Ischemia reduced peak contractions and increased Ca2+ levels equally in myocytes from both sexes. However, contraction amplitudes were reduced in reperfusion in male myocytes, while contractions recovered to exceed control levels in females (62.6±5.1 vs. 140.1±15.8%; p<0.05). Only 60% of male myocytes excluded trypan blue dye after ischemia and reperfusion, while all female cardiomyocytes excluded the dye (p<0.05). Parallel experiments were conducted in myocytes from ∼24-month-old female rats or 5–6-month-old rats that had an ovariectomy at 3–4 weeks of age. Beneficial effects of female sex on myocyte viability and contractile dysfunction in reperfusion were abolished in cells from 24-month-old females. Aged female myocytes also exhibited elevated intracellular Ca2+ and alternans in ischemia. Cells from ovariectomized rats displayed increased Ca2+ transients and spontaneous activity in ischemia compared to sham-operated controls. None of the myocytes from ovariectomized rats were viable after 15 minutes of ischemia, while 75% of sham cells remained viable at end of reperfusion (p<0.05). These findings demonstrate that cardiomyocytes from young adult females are more resistant to ischemia and reperfusion injury than cells from males. Age and OVX abolish these beneficial effects and induce Ca2+ dysregulation at the level of the cardiomyocyte. Thus, beneficial effects of estrogen in ischemia and reperfusion are mediated, in part, by effects on cardiomyocytes

Herbivory on planted dipterocarp seedlings in secondary logged forests and primary forests of Sabah, Malaysia

Journal ArticleLeaf defences, leaf nutritional quality and leaf expansion rates may vary with resource availabilities to plants. Such variation could affect rates of leaf loss to herbivores, particularly along the steep resource gradients in disturbed forests. Intraspecific and interspecific variation in leaf damage and leaf expansion rates were measured on dipterocarp seedlings planted into secondary forests 1, 5 and 15 y after logging, and in adjacent primary forest of Sabah, Malaysia. Herbivory rates or amounts of leaf damage were compared across habitats and species for expanding, recently expanded, and mature leaves of Shorea leprosula and Dryobalanops lanceolata (Dipterocarpaceae). In all four habitats, leaves of the faster growing S. leprosula sustained higher rates and amounts of leaf-area loss than did the tougher leaves of slower growing D. lanceolata. Expanding leaves accumulated more leaf-area loss per week than did mature leaves. In all habitats and in both species, more than 25% of expanding leaves disappeared entirely. Rates of leaf-area loss per week differed among habitats for expanding leaves but not for mature leaves. In a relatively open, 1-y-old logged forest, faster leaf expansion reduced the time leaves spent in the most vulnerable stage; however, in S. leprosula a greater rate of leaf area loss countered the shorter expansion time. Thus, leaves accumulated similar total damages across habitats, and herbivory did not produce differences among habitats in seedling growth or mortality. High levels of resources may increase both leaf palatability and leaf expansion rates, with counteracting effects on herbivory

On the direct indecomposability of infinite irreducible Coxeter groups and the Isomorphism Problem of Coxeter groups

In this paper we prove, without the finite rank assumption, that any irreducible Coxeter group of infinite order is directly indecomposable as an abstract group. The key ingredient of the proof is that we can determine, for an irreducible Coxeter group, the centralizers of the normal subgroups that are generated by involutions. As a consequence, we show that the problem of deciding whether two general Coxeter groups are isomorphic, as abstract groups, is reduced to the case of irreducible Coxeter groups, without assuming the finiteness of the number of the irreducible components or their ranks. We also give a description of the automorphism group of a general Coxeter group in terms of those of its irreducible components.Comment: 30 page

Cannabinoid receptor interacting protein suppresses agonist-driven CB1 receptor internalization and regulates receptor replenishment in an agonist-biased manner

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown clones to investigate gene dose effects of CRIP1a on CB1R plasma membrane expression. Results indicate that CP55940 or WIN55212-2 (10 nM, 5 min) reduced cell surface CB1R by a dynamin-and clathrin-dependent process, and this was attenuated by CRIP1a over-expression. CP55940-mediated cell surface CB1R loss was followed by a cycloheximide-sensitive recovery of surface receptors (30120 min), suggesting the requirement for new protein synthesis. In contrast, WIN55212-2-mediated cell surface CB(1)Rs recovered only in CRIP1a knockdown cells. Changes in CRIP1a expression levels did not affect a transient rimonabant (10 nM)mediated increase in cell surface CB(1)Rs, which is postulated to be as a result of rimonabant effects on \u27non-agonist-driven\u27 internalization. These studies demonstrate a novel role for CRIP1a in agonist-driven CB1R cell surface regulation postulated to occur by two mechanisms: 1) attenuating internalization that is agonist-mediated, but not that in the absence of exogenous agonists, and 2) biased agonist-dependent trafficking of de novo synthesized receptor to the cell surface

The cross-pathway control system regulates production of the secondary metabolite toxin, sirodesmin PL, in the ascomycete, Leptosphaeria maculans

<p>Abstract</p> <p>Background</p> <p>Sirodesmin PL is a secondary metabolite toxin made by the ascomycetous plant pathogen, <it>Leptosphaeria maculans</it>. The sirodesmin biosynthetic genes are clustered in the genome. The key genes are a non-ribosomal peptide synthetase, <it>sirP</it>, and a pathway-specific transcription factor, <it>sirZ</it>. Little is known about regulation of sirodesmin production.</p> <p>Results</p> <p>Genes involved in regulation of sirodesmin PL in <it>L. maculans </it>have been identified. Two hundred random insertional T-DNA mutants were screened with an antibacterial assay for ones producing low levels of sirodesmin PL. Three such mutants were isolated and each transcribed <it>sirZ </it>at very low levels. One of the affected genes had high sequence similarity to <it>Aspergillus fumigatus cpcA</it>, which regulates the cross-pathway control system in response to amino acid availability. This gene was silenced in <it>L. maculans </it>and the resultant mutant characterised. When amino acid starvation was artificially-induced by addition of 3-aminotriazole for 5 h, transcript levels of <it>sirP </it>and <it>sirZ </it>did not change in the wild type. In contrast, levels of <it>sirP </it>and <it>sirZ </it>transcripts increased in the silenced <it>cpcA </it>mutant. After prolonged amino acid starvation the silenced <it>cpcA </it>mutant produced much higher amounts of sirodesmin PL than the wild type.</p> <p>Conclusions</p> <p>Production of sirodesmin PL in <it>L. maculans </it>is regulated by the cross pathway control gene, <it>cpcA</it>, either directly or indirectly via the pathway-specific transcription factor, <it>sirZ</it>.</p

Recent progress in understanding immune activation in the pathogenesis in HIV-TB coinfection

Purpose of review Tuberculosis is the leading infectious cause of death worldwide, and HIV-1 the best recognized risk factor for active TB. This review focuses on immune complex formation; the interplay of type I and II interferon signaling; and T-cell activation in HIV–TB pathogenesis. Recent findings Circulating immune complexes and complement, and Fcγ signaling in whole blood act as early markers of TB disease in HIV-1-infected persons. HIV-1 is associated with a type I interferon response in whole blood, reducing the specificity of TB biomarkers dependent on type I and II interferon genes. Type I and type II interferons are implicated in both protection and TB disease, a protective outcome may depend on modulating these pathways. Whilst M. tuberculosis-specific CD4 T cells are preferentially depleted during HIV-1 infection, activation markers on M. tuberculosis-specific CD4 T cells, in particular HLA-DR, reflect immune activation and have promise as biomarkers of M. tuberculosis disease activity in individuals with HIV-1. Summary TB pathogenesis in HIV-1 involves a complex interaction of underlying activation of both the innate and adaptive immune systems. Further research is required to understand whether biomarkers of activation could be used to predict or quantify TB disease in the context of HIV-1 infection