2,342 research outputs found

    The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

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    The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway

    First Results from The GlueX Experiment

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    The GlueX experiment at Jefferson Lab ran with its first commissioning beam in late 2014 and the spring of 2015. Data were collected on both plastic and liquid hydrogen targets, and much of the detector has been commissioned. All of the detector systems are now performing at or near design specifications and events are being fully reconstructed, including exclusive production of π0\pi^{0}, η\eta and ω\omega mesons. Linearly-polarized photons were successfully produced through coherent bremsstrahlung and polarization transfer to the ρ\rho has been observed.Comment: 8 pages, 6 figures, Invited contribution to the Hadron 2015 Conference, Newport News VA, September 201

    Nutritive value of unconventional fibrous ingredients fed to Guinea pigs in the Democratic Republic of Congo

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    peer reviewedThe energy and protein value for Guinea pigs (GP) of 9 forages (7 dicots and 2 grasses) and 5 hay-based diets was determined. The apparent faecal digestibility of dry matter, organic matter, crude protein and energy was measured on GP housed in metabolic cages. The forages and the diets were digested in vitro using pepsin and pancreatin hydrolysis and gas fermentation test to simulate stomach, small intestine and large intestine, respectively. Most of the dicots had high digestible crude protein content (152–201 g/kg DM) and the 2 grasses showed lower values (80–85 g/kg DM). Digestible energy content of the forages ranged between 5.79 to 13.08 MJ/kg DM. None of the forage species or hay-based diets provided sufficient energy to supply the 11.7 MJ/kg metabolic energy requirements. The influence of intestinal fermentation on energy and protein values was highlighted by correlations (P<0.05) between in vivo and in vitro data, including gas fermentation. It is the first time that such relationships are reported in single-stomach animals

    The stigma of mental illness in Southern Ghana: attitudes of the urban population and patients’ views

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    PURPOSE: Stigma is a frequent accompaniment of mental illness leading to a number of detrimental consequences. Most research into the stigma connected to mental illness was conducted in the developed world. So far, few data exist on countries in sub-Saharan Africa and no data have been published on population attitudes towards mental illness in Ghana. Even less is known about the stigma actually perceived by the mentally ill persons themselves. METHOD: A convenience sample of 403 participants (210 men, mean age 32.4 ± 12.3 years) from urban regions in Accra, Cape Coast and Pantang filled in the Community Attitudes towards the Mentally Ill (CAMI) questionnaire. In addition, 105 patients (75 men, mean age 35.9 ± 11.0 years) of Ghana's three psychiatric hospitals (Accra Psychiatry Hospital, Ankaful Hospital, Pantang Hospital) answered the Perceived Stigma and Discrimination Scale. RESULTS: High levels of stigma prevailed in the population as shown by high proportions of assent to items expressing authoritarian and socially restrictive views, coexisting with agreement with more benevolent attitudes. A higher level of education was associated with more positive attitudes on all subscales (Authoritarianism, Social Restrictiveness, Benevolence and Acceptance of Community Based Mental Health Services). The patients reported a high degree of experienced stigma with secrecy concerning the illness as a widespread coping strategy. Perceived stigma was not associated with sex or age. DISCUSSION: The extent of stigmatising attitudes within the urban population of Southern Ghana is in line with the scant research in other countries in sub-Saharan Africa and mirrored by the experienced stigma reported by the patients. These results have to be seen in the context of the extreme scarcity of resources within the Ghanaian psychiatric system. Anti-stigma efforts should include interventions for mentally ill persons themselves and not exclusively focus on public attitudes

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
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