382 research outputs found
A brain-infecting parasite impacts host metabolism both during exposure and after infection is established
Metabolic costs associated with parasites should not be limited to established infections. Even during initial exposure to questing and attacking parasites, hosts can enact behavioural and physiological responses that could also incur metabolic costs. However, few studies have measured these costs directly. Hence, little is known about metabolic costs arising from parasite exposure. Furthermore, no one has yet measured whether and how previous infection history modulates metabolic responses to parasite exposure. Here, using the California killifish Fundulus parvipinnis and its brainâinfecting parasite Euhaplorchis californiensis, we quantified how killifish metabolism, behaviour and osmoregulatory phenotype changed upon acute exposure to parasite infectious stages (i.e. cercariae), and with longâterm infection. Exposure to cercariae caused both naĂŻve and longâterm infected killifish to acutely increase their metabolic rate and activity, indicating detection and response to parasite infectious stages. Additionally, these metabolic and behavioural effects were moderately stronger in longâterm infected hosts than naĂŻve killifish, suggesting that hosts may develop learned behavioural responses, nociceptor sensitization and/or acute immune mechanisms to limit new infections. Although established infection altered the metabolic response to parasite exposure, established infection did not alter standard metabolic rate, routine metabolic rate, maximum metabolic rate, aerobic scope or citrate synthase enzyme activity. Unexpectedly, established infection reduced lactate dehydrogenase enzyme activity in killifish brains and relative Na+/K+âATPase abundance in gills, suggesting novel mechanisms by which E. californiensis may alter its hosts\u27 behaviour and osmoregulation. Thus, we provide empirical evidence that parasites can disrupt the metabolism of their host both during parasite exposure and after infection is established. This response may be modulated by previous infection history, with probable knockâon effects for host performance, brain energy metabolism, osmoregulation and ecology.
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Transcriptional profiling of degraded RNA in cryopreserved and fixed tissue samples obtained at autopsy
BACKGROUND: Traditional multiplexed gene expression methods require well preserved, intact RNA. Such specimens are difficult to acquire in clinical practice where formalin fixation is the standard procedure for processing tissue. Even when special handling methods are used to obtain frozen tissue, there may be RNA degradation; for example autopsy samples where degradation occurs both pre-mortem and during the interval between death and cryopreservation. Although specimens with partially degraded RNA can be analyzed by qRT-PCR, these analyses can only be done individually or at low levels of multiplexing and are laborious and expensive to run for large numbers of RNA targets. METHODS: We evaluated the ability of the cDNA-mediated Annealing, Selection, extension, and Ligation (DASL) assay to provide highly multiplexed analyses of cryopreserved and formalin fixed, paraffin embedded (FFPE) tissues obtained at autopsy. Each assay provides data on 1536 targets, and can be performed on specimens with RNA fragments as small as 60 bp. RESULTS: The DASL performed accurately and consistently with cryopreserved RNA obtained at autopsy as well as with RNA extracted from formalin-fixed paraffin embedded tissue that had a cryopreserved mirror image specimen with high quality RNA. In FFPE tissue where the cryopreserved mirror image specimen was of low quality the assay performed reproducibly on some but not all specimens. CONCLUSION: The DASL assay provides reproducible results from cryopreserved specimens and many FFPE specimens obtained at autopsy. Gene expression analyses of these specimens may be especially valuable for the study of non-cancer endpoints, where surgical specimens are rarely available
Fertility and economic instability: the role of unemployment and job displacement
In this paper, we study the separate effects of unemployment and job displacement on fertility in a sample of white collar women in Austria. Using an instrumental variable approach, we show that unemployment incidence as such has no negative effect on fertility decisions, but the very fact of being displaced from a career-oriented job has. Fertility rates for women affected by a firm closure are significantly below those of a control group, even after 6 years, and this is so irrespective of the incidence or the duration of the associated unemployment spell
"Which sexuality? Which service?" : bisexual young people\u27s experiences with youth, queer and mental health services in Australia
Gene expression profiling revealed novel mechanism of action of Taxotere and Furtulon in prostate cancer cells
BACKGROUND: Both Taxotere and Capecitabine have shown anti-cancer activity against various cancers including prostate cancer. In combination, Taxotere plus Capecitabine has demonstrated higher anti-cancer activity in advanced breast cancers. However, the molecular mechanisms of action of Taxotere and Capecitabine have not been fully elucidated in prostate cancer. METHODS: The total RNA from PC3 and LNCaP prostate cells untreated and treated with 2 nM Taxotere, 110 ÎŒM Furtulon (active metabolite of Capecitabine), or 1 nM Taxotere plus 50 ÎŒM Furtulon for 6, 36, and 72 hours, was subjected to Affymetrix Human Genome U133A Array analysis. Real-time PCR and Western Blot analysis were conducted to confirm microarray data. RESULTS: Taxotere and Furtulon down-regulated some genes critical for cell proliferation, cell cycle progression, transcription factor, cell signaling, and oncogenesis, and up-regulated some genes related to the induction of apoptosis, cell cycle arrest, and differentiation in both cell lines. Taxotere and Furtulon also up-regulated some genes responsible for chemotherapeutic resistance, suggesting the induction of cancer cell resistance to these agents. CONCLUSIONS: Taxotere and Furtulon caused the alternation of a large number of genes, many of which may contribute to the molecular mechanisms by which Taxotere and Furtulon inhibit the growth of prostate cancer cells. This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against prostate cancer
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