211 research outputs found

    Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria.

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    Mycobacteria share with other actinomycetes the ability to produce large quantities of triacylglycerol (TAG), which accumulate as intracytoplasmic lipid inclusions (ILI) also known as lipid droplets (LD). Mycobacterium tuberculosis (M. tb), the etiologic agent of tuberculosis, acquires fatty acids from the human host which are utilized to synthesize TAG, subsequently stored in the form of ILI to meet the carbon and nutrient requirements of the bacterium during long periods of persistence. However, environmental factors governing mycobacterial ILI formation and degradation remain poorly understood. Herein, we demonstrated that in the absence of host cells, carbon excess and nitrogen starvation promote TAG accumulation in the form of ILI in M. smegmatis and M. abscessus, used as surrogate species of M. tb. Based on these findings, we developed a simple and reversible in vitro model to regulate ILI biosynthesis and hydrolysis in mycobacteria. We also showed that TAG formation is tgs1 dependent and that lipolytic enzymes mediate TAG breakdown. Moreover, we confirmed that the nitrogen-deprived and ILI-rich phenotype was associated with an increased tolerance towards several drugs used for treating mycobacterial infections. Importantly, we showed that the presence of ILI substantially enhanced the bacterial burden and granuloma abundance in zebrafish embryos infected with lipid-rich M. abscessus as compared to embryos infected with lipid-poor M. abscessus, suggesting that ILI are actively contributing to mycobacterial virulence and pathogenesis

    Effects of financial incentives for treatment supporters on tuberculosis treatment outcomes in Swaziland: a pragmatic interventional study

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    Background: Swaziland has the highest national incidence of tuberculosis (TB) in the world, with treatment success rates well below the 85 % international target. Treatment support as part of comprehensive TB services is a core component of the Stop TB Strategy. This study investigated the effects of financial incentives for treatment supporters on TB treatment outcomes in Swaziland. Methods: This was a controlled study that compared treatment outcomes for patients with a treatment supporter who received or did not receive a financial incentive. Results: The intervention group had a higher chance of treatment success as compared with the control group: 73 % (95 % confidence intervals [CIs] 66–80 %) versus 60 % (95 % CIs 57–64 %), respectively, p = 0.003. This improvement remained significant when treatment success rates were adjusted for differences in baseline characteristics, with the effect of incentivised treatment supporters on treatment outcomes having an odds ratio (OR) of 1.8. There was also a significant improvement in the death rate in the intervention group, as compared with the control group (10.6 versus 23.5 %, p = <0.001). Conclusion: Incentives provided to TB treatment supporters appear to significantly improve TB treatment outcomes. Incentivising treatment support may be appropriate as an effective addition to support and supervision measures (199 words)

    The Lantern Vol. 18, No. 1, Fall 1949

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    • Want, an Old Freedom Unused • Is History Bunk? • How Things Grow • A Real Gone Poem • Hish Proves Himself • Death? Not Yet! • On the Neglect of Victorian Literature • The Tradition Lives On • To the Other Side • Autumn\u27s Panorama • Autumn Treasure • A Walk • Leaves • The Moment • Dawn • Sentiments • Dustinghttps://digitalcommons.ursinus.edu/lantern/1049/thumbnail.jp

    Association between Chronotype and Nutritional, Clinical and Sociobehavioral Characteristics of Adults Assisted by a Public Health Care System in Brazil

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    Chronotype (CT) has been associated with predisposition to chronic noncommunicable diseases (CNCDs), such as diabetes mellitus and obesity. However, the effects of CT on individuals assisted by public health systems (PHSs) in middle-up economies are still poorly explored. The objective of this study was to evaluate the relationship between CT and clinical, sociobehavioral and nutritional aspects in adults assisted by a PHS in Brazil. This is a population-based cross-sectional study. The sample consisted of 380 individuals, selected through probabilistic sampling by clusters, in all health units in a city of approximately 100 thousand inhabitants. Data collection was performed during home visits, by means of general and nutritional interviews, anthropometric measurements and the Morningness–Eveningness Questionnaire (MEQ). Statistical analysis comprised chi-square test and principal component analysis (CPA) followed by Fisher’s discriminant analysis to determine aspects associated with each CT (morning, evening or intermediate). With the aim of explaining the variation in the CT scores, the consumption of micronutrients (corrected to the total energy intake) and other individual and sociodemographic variables were used as explanatory factors in the adjustment of a linear regression model. The morning group was characterized by older men, with less than eight years of schooling, with low body mass index (BMI) and with low intake of omega-6, omega-3, sodium, zinc, thiamine, pyridoxine and niacin. The evening group, on the other hand, was composed of younger individuals, with a high consumption of these same nutrients, with high BMI and a higher frequency of heart diseases (p < 0.05). It was concluded that most morning CT individuals were elderly thin males with lower consumption of omega-6 and -3, sodium, zinc, thiamine, pyridoxine and niacin, whereas evening individuals were younger, had higher BMI and had higher consumption of the studied micronutrients. The identification of circadian and behavioral risk groups can help to provide preventive and multidisciplinary health promotion measures

    The Lantern Vol. 18, No. 1, Fall 1949

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    • Want, an Old Freedom Unused • Is History Bunk? • How Things Grow • A Real Gone Poem • Hish Proves Himself • Death? Not Yet! • On the Neglect of Victorian Literature • The Tradition Lives On • To the Other Side • Autumn\u27s Panorama • Autumn Treasure • A Walk • Leaves • The Moment • Dawn • Sentiments • Dustinghttps://digitalcommons.ursinus.edu/lantern/1049/thumbnail.jp

    Time course analysis of the extracellular proteome of Aspergillus nidulans growing on sorghum stover

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    Background: Fungi are important players in the turnover of plant biomass because they produce a broad range of degradative enzymes. Aspergillus nidulans, a well-studied saprophyte and close homologue to industrially important species such as A. niger and A. oryzae, was selected for this study.Results: A. nidulans was grown on sorghum stover under solid-state culture conditions for 1, 2, 3, 5, 7 and 14 days. Based on analysis of chitin content, A. nidulans grew to be 4-5% of the total biomass in the culture after 2 days and then maintained a steady state of 4% of the total biomass for the next 12 days. A hyphal mat developed on the surface of the sorghum by day one and as seen by scanning electron microscopy the hyphae enmeshed the sorghum particles by day 5. After 14 days hyphae had penetrated the entire sorghum slurry. Analysis (1-D PAGE LC-MS/MS) of the secretome of A. nidulans, and analysis of the breakdown products from the sorghum stover showed a wide range of enzymes secreted. A total of 294 extracellular proteins were identified with hemicellulases, cellulases, polygalacturonases, chitinases, esterases and lipases predominating the secretome. Time course analysis revealed a total of 196, 166, 172 and 182 proteins on day 1, 3, 7 and 14 respectively. The fungus used 20% of the xylan and cellulose by day 7 and 30% by day 14. Cellobiose dehydrogenase, feruloyl esterases, and CAZy family 61 endoglucanases, all of which are thought to reduce the recalcitrance of biomass to hydrolysis, were found in high abundance.Conclusions: Our results show that A. nidulans secretes a wide array of enzymes to degrade the major polysaccharides and lipids (but probably not lignin) by 1 day of growth on sorghum. The data suggests simultaneous breakdown of hemicellulose, cellulose and pectin. Despite secretion of most of the enzymes on day 1, changes in the relative abundances of enzymes over the time course indicates that the set of enzymes secreted is tailored to the specific substrates available. Our findings reveal that A. nidulans is capable of degrading the major polysaccharides in sorghum without any chemical pre-treatment.Peer reviewedBiochemistry and Molecular BiologyMicrobiology and Molecular Genetic

    The co-operative university: Labour, property and pedagogy

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    I begin this article by discussing the recent work of academics and activists to identify the advantages and issues relating to co-operative forms of higher education, and then focus on the ‘worker co-operative’ organisational form and its applicability and suitability to the governance of and practices within higher educational institutions. Finally, I align the values and principles of worker co-ops with the critical pedagogic framework of ‘Student as Producer’. Throughout I employ the work of Karl Marx to theorise the role of labour and property in a ‘co-operative university’, drawing particularly on later Marxist writers who argue that Marx’s labour theory of value should be understood as a critique of labour under capitalism, rather than one developed from the standpoint of labour

    The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway

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    Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA). AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1. In addition, AIPL1 antagonised the NUB1-mediated degradation of the model FAT10 conjugate, FAT10-DHFR, and pathogenic mutations of AIPL1 were defective in inhibiting this degradation. While all AIPL1 mutants tested still bound FAT10-DHFR, there was a close correlation between the ability of the mutants to interact with NUB1 and their ability to prevent NUB1-mediated degradation. Interestingly, AIPL1 also co-immunoprecipitated the E1 activating enzyme for FAT10, UBA6, suggesting AIPL1 may have a role in directly regulating the FAT10 conjugation machinery. These studies are the first to implicate FAT10 in retinal cell biology and LCA pathogenesis, and reveal a new role of AIPL1 in regulating the FAT10 pathway

    Nurse led, primary care based antiretroviral treatment versus hospital care: a controlled prospective study in Swaziland

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    <p>Abstract</p> <p>Background</p> <p>Antiretroviral treatment services delivered in hospital settings in Africa increasingly lack capacity to meet demand and are difficult to access by patients. We evaluate the effectiveness of nurse led primary care based antiretroviral treatment by comparison with usual hospital care in a typical rural sub Saharan African setting.</p> <p>Methods</p> <p>We undertook a prospective, controlled evaluation of planned service change in Lubombo, Swaziland. Clinically stable adults with a CD4 count > 100 and on antiretroviral treatment for at least four weeks at the district hospital were assigned to either nurse led primary care based antiretroviral treatment care or usual hospital care. Assignment depended on the location of the nearest primary care clinic. The main outcome measures were clinic attendance and patient experience.</p> <p>Results</p> <p>Those receiving primary care based treatment were less likely to miss an appointment compared with those continuing to receive hospital care (RR 0·37, <it>p </it>< 0·0001). Average travel cost was half that of those receiving hospital care (<it>p </it>= 0·001). Those receiving primary care based, nurse led care were more likely to be satisfied in the ability of staff to manage their condition (RR 1·23, <it>p </it>= 0·003). There was no significant difference in loss to follow-up or other health related outcomes in modified intention to treat analysis. Multilevel, multivariable regression identified little inter-cluster variation.</p> <p>Conclusions</p> <p>Clinic attendance and patient experience are better with nurse led primary care based antiretroviral treatment care than with hospital care; health related outcomes appear equally good. This evidence supports efforts of the WHO to scale-up universal access to antiretroviral treatment in sub Saharan Africa.</p
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