1,328 research outputs found

    Shorter Leukocyte Telomere Length in Relation to Presumed Nonalcoholic Fatty Liver Disease in Mexican-American Men in NHANES 1999-2002.

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    Leukocyte telomere length is shorter in response to chronic disease processes associated with inflammation such as diabetes mellitus and coronary artery disease. Data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002 was used to explore the relationship between leukocyte telomere length and presumed NAFLD, as indicated by elevated serum alanine aminotransferase (ALT) levels, obesity, or abdominal obesity. Logistic regression models were used to evaluate the relationship between telomere length and presumed markers of NAFLD adjusting for possible confounders. There was no relationship between elevated ALT levels, abdominal obesity, or obesity and telomere length in adjusted models in NHANES (OR 1.13, 95% CI 0.48-2.65; OR 1.17, 95% CI 0.52-2.62, resp.). Mexican-American men had shorter telomere length in relation to presumed NAFLD (OR 0.07, 95% CI 0.006-0.79) and using different indicators of NAFLD (OR 0.012, 95% CI 0.0006-0.24). Mexican origin with presumed NAFLD had shorter telomere length than men in other population groups. Longitudinal studies are necessary to evaluate the role of telomere length as a potential predictor to assess pathogenesis of NALFD in Mexicans

    Stereotactic guidance for navigated percutaneous sacroiliac joint fusion.

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    Arthrodesis of the sacroiliac joint (SIJ) for surgical treatment of SIJ dysfunction has regained interest among spine specialists. Current techniques described in the literature most often utilize intraoperative fluoroscopy to aid in implant placement; however, image guidance for SIJ fusion may allow for minimally invasive percutaneous instrumentation with more precise implant placement. In the following cases, we performed percutaneous stereotactic navigated sacroiliac instrumentation using O-arm® multidimensional surgical imaging with StealthStation® navigation (Medtronic, Inc. Minneapolis, MN). Patients were positioned prone and an image-guidance reference frame was placed contralateral to the surgical site. O-arm® integrated with StealthStation® allowed immediate auto-registration. The skin incision was planned with an image-guidance probe. An image-guided awl, drill and tap were utilized to choose a starting point and trajectory. Threaded titanium cage(s) packed with autograft and/or allograft were then placed. O-arm® image-guidance allowed for implant placement in the SIJ with a small skin incision. However, we could not track the cage depth position with our current system, and in one patient, the SIJ cage had to be revised secondary to the anterior breach of sacrum

    Functional Evaluation of Plasmodium Export Signals in Plasmodium berghei Suggests Multiple Modes of Protein Export

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    The erythrocytic stage development of malaria parasites occurs within the parasitophorous vacuole inside the infected-erythrocytes, and requires transport of several parasite-encoded proteins across the parasitophorous vacuole to several locations, including the cytosol and membrane of the infected cell. These proteins are called exported proteins; and a large number of such proteins have been predicted for Plasmodium falciparum based on the presence of an N-terminal motif known as the Plasmodium export element (PEXEL) or vacuolar transport signal (VTS), which has been shown to mediate export. The majority of exported proteins contain one or more transmembrane domains at the C-terminus and one of three types of N-terminus domain architectures. (1) The majority, including the knob-associated histidine rich protein (KAHRP), contain a signal/hydrophobic sequence preceding the PEXEL/VTS motif. (2) Other exported proteins, including the P. berghei variant antigen family bir and the P. falciparum skeleton binding protein-1, do not appear to contain a PEXEL/VTS motif. (3) The P. falciparum erythrocyte membrane protein-1 (PfEMP1) family lacks a signal/hydrophobic sequence before the motif. These different domain architectures suggest the presence of multiple export pathways in malaria parasites. To determine if export pathways are conserved in plasmodia and to develop an experimental system for studying these processes, we investigated export of GFP fused with N- and C-terminus putative export domains in the rodent malaria parasite P. berghei. Export was dependent on specific N- and C-terminal domains. Constructs with a KAHRP-like or bir N-terminus, but not the PfEMP1 N-terminus, exported GFP into the erythrocyte. The C-terminus of a P. falciparum variant antigen rifin prevented GFP export by the KAHRP-like N-terminus. In contrast, GFP chimeras containing KAHRP-like N-termini and the PfEMP1 C-terminus were exported to the surface of erythrocytes. Taken together, these results suggest that proteins with KAHRP-like architecture follow a common export pathway, but that PfEMP1s utilize an alternative pathway. Functional validation of common putative export domains of malaria parasites in P. berghei provides an alternative and simpler system to investigate export mechanisms

    Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity.

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    Falcipain-2 and falcipain-3 are critical hemoglobinases of Plasmodium falciparum, the most virulent human malaria parasite. We have determined the 2.9 A crystal structure of falcipain-2 in complex with the epoxysuccinate E64 and the 2.5 A crystal structure of falcipain-3 in complex with the aldehyde leupeptin. These complexes represent the first crystal structures of plasmodial cysteine proteases with small molecule inhibitors and the first reported crystal structure of falcipain-3. Our structural analyses indicate that the relative shape and flexibility of the S2 pocket are affected by a number of discrete amino acid substitutions. The cumulative effect of subtle differences, including those at "gatekeeper" positions, may explain the observed kinetic differences between these two closely related enzymes

    Private Credit Markets in Paris 1690-1840

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    Relying on a large sample of private and public loan contracts taken from Parisian notarial records, this article examines the private borrowers and lenders who participated in the credit market between 1690 and 1840. It explains the important role notaries played in the market, describes the types of loans available to borrowers and lenders, stresses the importance of the life cycle in explaining the recourse to indebtedness, and ends with a discussion of the difficulties lenders had in assessing creditworthiness

    Révolution et évolution: Les marchés du crédit notarié en France, 1780-1840

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    Cet article cherche à comprendre comment se créent (ou se détruisent) les techniques de savoir des marchés du crédit ainsi que les institutions auxquelles s'adosse ce capital social essentiel à leur fonctionnement. Il examine soixante-sept marchés locaux répartis dans toute la France en saisissant leur évolution à partir de trois coupes situées de part et d'autre de ce choc majeur qu'est la Révolution pour pouvoir en suivre les effets. Le crédit se réorganise alors non dans le cadre de petites régions ni dans un espace national unifié, mais plutôt en deux grands ensembles - l'un au Nord, l'autre au Sud - où des pratiques du crédit distinctes évoluent séparément. Comme chacun d'eux, loin d'être homogène, se hiérarchise entre ville et campagnes, il en résulte quatre systèmes qui se repèrent aussi bien si l'on observe les instruments de crédit, les intermédiaires ou les circuits de formation que ces derniers se donnent. Pour expliquer cette diversité, il faut accepter que les institutions formelles et informelles se déploient dans l'espace d'une façon qui dépend de l'activité des marchés mais aussi de l'inégale répartition de la richesse. This article seeks to explain how the information technology that is essential for the operation of credit markets is created or destroyed. Information technology of this sort is a form of social capital, and the article also seeks to understand how institutions linked to such social capital arise or disappear. It does so by looking at 67 different credit markets scattered throughout France and examining their evolution both before and after the French Revolution. The aim is to follow the consequences of the great changes that the Revolution brought about. It turns out that the institutions of credit markets were not uniformed across France, but they were not peculiar to each local market either. Rather, there were two distinct institutional patterns - one found in Northern France and the other typical of the South - and in each region the institutions of credit markets evolved in a different way. Institutions were also different in the city and in the countryside, and as a result there were really four distinct systems of credit, each with distinctive types of loans and financial intermediaries, who were trained in dissimilar ways. The existence of such differences implies that institutions depended on the volume of lending in each market and also on the level of inequality
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