243 research outputs found

    Modulation of phosphofructokinase (PFK) from Setaria cervi, a bovine filarial parasite, by different effectors and its interaction with some antifilarials

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    <p>Abstract</p> <p>Background</p> <p>Phosphofructokinase (ATP: D-fructose-6-phosphate-1-phosphotransferase, EC 2.7.1.11, PFK) is of primary importance in the regulation of glycolytic flux. This enzyme has been extensively studied from mammalian sources but relatively less attention has been paid towards its characterization from filarial parasites. Furthermore, the information about the response of filarial PFK towards the anthelmintics/antifilarial compounds is lacking. In view of these facts, PFK from <it>Setaria cervi</it>, a bovine filarial parasite having similarity with that of human filarial worms, was isolated, purified and characterized.</p> <p>Results</p> <p>The <it>S. cervi </it>PFK was cytosolic in nature. The adult parasites (both female and male) contained more enzyme activity than the microfilarial (Mf) stage of <it>S. cervi</it>, which exhibited only 20% of total activity. The <it>S. cervi </it>PFK could be modulated by different nucleotides and the response of enzyme to these nucleotides was dependent on the concentrations of substrates (F-6-P and ATP). The enzyme possessed wide specificity towards utilization of the nucleotides as phosphate group donors. <it>S. cervi </it>PFK showed the presence of thiol group(s) at the active site of the enzyme, which could be protected from inhibitory action of para-chloromercuribenzoate (p-CMB) up to about 76% by pretreatment with cysteine or β-ME. The sensitivity of PFK from <it>S. cervi </it>towards antifilarials/anthelmintics was comparatively higher than that of mammalian PFK. With suramin, the Ki value for rat liver PFK was 40 times higher than PFK from <it>S. cervi</it>.</p> <p>Conclusions</p> <p>The results indicate that the activity of filarial PFK may be modified by different effectors (such as nucleotides, thiol group reactants and anthelmintics) in filarial worms depending on the presence of varying concentrations of substrates (F-6-P and ATP) in the cellular milieu. It may possess thiol group at its active site responsible for catalysis. Relatively, 40 times higher sensitivity of filarial PFK towards suramin as compared to the analogous enzyme from the mammalian system indicates that this enzyme could be exploited as a potential chemotherapeutic target against filariasis.</p

    Potential climatic transitions with profound impact on Europe

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    We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

    Mental distress, alcohol use and help-seeking among medical and business students: a cross-sectional comparative study

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    <p>Abstract</p> <p>Background</p> <p>Stress and distress among medical students are thoroughly studied and presumed to be particularly high, but comparative studies including other student groups are rare.</p> <p>Methods</p> <p>A web-based survey was distributed to 500 medical students and 500 business students. We compared levels of study stress (HESI), burnout (OLBI), alcohol habits (AUDIT) and depression (MDI), and analysed their relationship with self-assessed mental health problems by logistic regression, with respect to gender.</p> <p>Results</p> <p>Medical students' response rate was 81.6% and that of business students 69.4%. Business students scored higher on several study stress factors and on disengagement. Depression (OR 0.61, CI<sub>95 </sub>0.37;0.98) and harmful alcohol use (OR 0.55, CI<sub>95 </sub>0.37; 0.75) were both less common among medical students. However, harmful alcohol use was highly prevalent among male students in both groups (medical students 28.0%, business students 35.4%), and among female business students (25.0%). Mental health problems in need of treatment were equally common in both groups; 22.1% and 19.3%, respectively, and was associated with female sex (OR 2.01, CI<sub>95 </sub>1.32;3.04), exhaustion (OR 2.56, CI<sub>95 </sub>1.60;4.10), lower commitment to studies (OR 1.95, CI<sub>95 </sub>1.09;3.51) and financial concerns (OR 1.81 CI<sub>95 </sub>1.18;2.80)</p> <p>Conclusions</p> <p>Medical students may not be more stressed than other high achieving student populations. The more cohesive structure of medical school and a higher awareness of a healthy lifestyle may be beneficial factors.</p

    Burnout and psychiatric morbidity among medical students entering clinical training: a three year prospective questionnaire and interview-based study

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    BACKGROUND: Mental distress among medical students is often reported. Burnout has not been studied frequently and studies using interviewer-rated diagnoses as outcomes are rarely employed. The objective of this prospective study of medical students was to examine clinically significant psychiatric morbidity and burnout at 3(rd )year of medical school, considering personality and study conditions measured at 1(st )year. METHODS: Questionnaires were sent to 127 first year medical students who were then followed-up at 3(rd )year of medical school. Eighty-one of 3(rd )year respondents participated in a diagnostic interview. Personality (HP5-i) and Performance-based self-esteem (PBSE-scale) were assessed at first year, Study conditions (HESI), Burnout (OLBI), Depression (MDI) at 1(st )and 3(rd )years. Diagnostic interviews (MINI) were used at 3(rd )year to assess psychiatric morbidity. High and low burnout at 3(rd )year was defined by cluster analysis. Logistic regressions were used to identify predictors of high burnout and psychiatric morbidity, controlling for gender. RESULTS: 98 (77%) responded on both occasions, 80 (63%) of these were interviewed. High burnout was predicted by Impulsivity trait, Depressive symptoms at 1(st )year and Financial concerns at 1(st )year. When controlling for 3(rd )year study conditions, Impulsivity and concurrent Workload remained. Of the interviewed sample 21 (27%) had a psychiatric diagnosis, 6 of whom had sought help. Unadjusted analyses showed that psychiatric morbidity was predicted by high Performance-based self-esteem, Disengagement and Depression at 1(st )year, only the later remained significant in the adjusted analysis. CONCLUSION: Psychiatric morbidity is common in medical students but few seek help. Burnout has individual as well as environmental explanations and to avoid it, organisational as well as individual interventions may be needed. Early signs of depressive symptoms in medical students may be important to address. Students should be encouraged to seek help and adequate facilities should be available

    Adenoviruses in Lymphocytes of the Human Gastro-Intestinal Tract

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    Objective: Persistent adenoviral shedding in stools is known to occur past convalescence following acute adenoviral infections. We wished to establish the frequency with which adenoviruses may colonize the gut in normal human subjects. Methods: The presence of adenoviral DNA in intestinal specimens obtained at surgery or autopsy was tested using a nested PCR method. The amplified adenoviral DNA sequences were compared to each other and to known adenoviral species. Lamina propria lymphocytes (LPLs) were isolated from the specimens and the adenoviral copy numbers in the CD4+ and CD8+ fractions were determined by quantitative PCR. Adenoviral gene expression was tested by amplification of adenoviral mRNA. Results: Intestinal tissue from 21 of 58 donors and LPLs from 21 of 24 donors were positive for the presence of adenoviral DNA. The majority of the sequences could be assigned to adenoviral species E, although species B and C sequences were also common. Multiple sequences were often present in the same sample. Forty-one non-identical sequences were identified from 39 different tissue donors. Quantitative PCR for adenoviral DNA in CD4+ and CD8+ fractions of LPLs showed adenoviral DNA to be present in both cell types and ranged from a few hundred to several million copies per million cells on average. Active adenoviral gene expression as evidenced by the presence of adenoviral messenger RNA in intestinal lymphocytes was demonstrated in 9 of the 11 donors tested

    An siRNA Screen in Pancreatic Beta Cells Reveals a Role for Gpr27 in Insulin Production

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    The prevalence of type 2 diabetes in the United States is projected to double or triple by 2050. We reasoned that the genes that modulate insulin production might be new targets for diabetes therapeutics. Therefore, we developed an siRNA screening system to identify genes important for the activity of the insulin promoter in beta cells. We created a subclone of the MIN6 mouse pancreatic beta cell line that expresses destabilized GFP under the control of a 362 base pair fragment of the human insulin promoter and the mCherry red fluorescent protein under the control of the constitutively active rous sarcoma virus promoter. The ratio of the GFP to mCherry fluorescence of a cell indicates its insulin promoter activity. As G protein coupled receptors (GPCRs) have emerged as novel targets for diabetes therapies, we used this cell line to screen an siRNA library targeting all known mouse GPCRs. We identified several known GPCR regulators of insulin secretion as regulators of the insulin promoter. One of the top positive regulators was Gpr27, an orphan GPCR with no known role in beta cell function. We show that knockdown of Gpr27 reduces endogenous mouse insulin promoter activity and glucose stimulated insulin secretion. Furthermore, we show that Pdx1 is important for Gpr27's effect on the insulin promoter and insulin secretion. Finally, the over-expression of Gpr27 in 293T cells increases inositol phosphate levels, while knockdown of Gpr27 in MIN6 cells reduces inositol phosphate levels, suggesting this orphan GPCR might couple to Gq/11. In summary, we demonstrate a MIN6-based siRNA screening system that allows rapid identification of novel positive and negative regulators of the insulin promoter. Using this system, we identify Gpr27 as a positive regulator of insulin production

    Haemato-oncology and burnout: an Italian survey

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    This cross-sectional survey aimed to evaluate the prevalence of burnout and estimated psychiatric disorders among haemato-oncology healthcare professionals in Italy. The aspects of work that respondents perceive as stressful and satisfying have also been examined. The assessments were made using the Maslach Burnout Inventory (MBI), General Health Questionnaire and a study-specific questionnaire. Logistic regression models were applied to show associations between different sources of work-related stress and burnout. Three hundred and eighty-seven out of 440 (87.95%) returned their questionnaires. The scores on MBI subscales indicate a high level of emotional exhaustion in 32.2% of the physicians and 31.9% of the nurses; a high level of Depersonalisation in 29.8 and 23.6%, respectively; and a low level of personal accomplishment in 12.4 and 15.3% respectively. The estimated prevalence of psychiatric disorders was 36.4% in physicians and 28.8% in nurses. Statistical analysis confirmed age, sex, personal dissatisfaction, physical tiredness and working with demanding patients to be associated with burnout. In conclusion, haemato-oncology healthcare professionals report a level of burnout and estimated psychiatric morbidity comparable to other oncological areas. Knowledge of the mechanisms of burnout and preventing and dealing with them is therefore a fundamental requirement for the improvement of quality in health services and job satisfaction

    Natural Infection of the Ground Squirrel (Spermophilus spp.) with Echinococcus granulosus in China

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    Echinococcus granulosus and E. multilocularis are important zoonotic pathogens that cause serious disease in humans. E. granulosus can be transmitted through sylvatic cycles, involving wild carnivores and ungulates; or via domestic cycles, usually involving dogs and farm livestock. E. multilocularis is primarily maintained in a sylvatic life-cycle between foxes and rodents. As part of extensive investigations that we undertook to update available epidemiological data and to monitor the transmission patterns of both E. granulosus and E. mulilocularis in Ningxia Hui Autonomous Region (NHAR) in northwest China, we captured small mammals on the southern slopes of Yueliang Mountain, Xiji, an area co-endemic for human alveolar echinococcosis and cystic echinococcosis. Of 500 trapped small mammals (mainly ground squirrels; Spermophilus dauricus/alashanicus), macroscopic cyst-like lesions (size range 1–10 mm) were found on the liver surface of approximately 10% animals. One of the lesions was shown by DNA analysis to be caused by E. granulosus and by histology to contain viable protoscoleces. This is the first report of a natural infection of the ground squirrel with E. granulosus. We have no definitive proof of a cycle involving ground squirrels and dogs/foxes but it is evident that there is active E. granulosus transmission occurring in this area

    What lies between market and hierarchy? Insights from internalization theory and global value chain theory

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    In this paper, we suggest that internalization theory might be extended by incorporating complementary insights from GVC theory. More specifically, we argue that internalization theory can explain why lead firms might wish to externalize selected activities, but that it is largely silent on the mechanisms by which those lead firms might exercise control over the resultant externalized relationships with their GVC partners. We advance an explanation linking the choice of control mechanism to two factors: power asymmetries between the lead firms and their GVC partners, and the degree of codifiability of the information to be exchanged in the relationship
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