Measurement of the latent variable in latent trait analysis of binary data

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Behaviour of the likelihood function in latent trait analysis of binary data

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Analysis of the effects of K-RasG12V and K-RasG13D on the cell cycle

p21 Ras is small protein with GTPase activity that regulates proliferation, differentiation and apoptosis in all cell types. The three major isoforms of Ras (H-, K- and N-Ras) differing only for the last 24 aminoacids have different post-translational modifications that lead to localization in diverse plasma membrane microdomains and downstream activation of alternative pathways of signal transduction. This might explain, at least in part, the different biological effects of the Ras isoforms in the cells. Ras mutations are a common event in several tumours and in almost all cases they are point mutations in codons 12 or 13, and rarely in codon 61. These mutations lead to a constitutively active protein by inactivating the GTPase activity. However, data show in different primary and metastatic tumors that not only mutations of different isoforms of Ras, but also mutations in different codons or different mutations in the same codon of the same isoform of Ras have diverse biological consequences. In particular, in colorectal carcinomas (CRCs) Ras mutations are quite frequent and affect mainly K-Ras, usuallly already at a early stage of tumor development. To shed more light on the molecular mechanisms responsible for the different effects of Ras mutations, we have used stable clones of HT-29 (a human colorectal adenocarcinoma cell line in which the endogenous Ras genes are wild type) transfected with cDNAs codifying: K-RasG12V (clone K12) and K-RasG13D (clone K13) under the control of a Mifepristone-inducible promoter. We found that the expression of K-Ras mutated in two different codons (codon 12 or codon 13) induces specific and different effects on the growth rate. Cytofluorimetric analysis shows also a differential effect on the cell cycle. Finally, Western analysis shows a significant increase in the expression of the cell cycle inhibitor protein p21 in response to induction of K-RasG12V or K-RasG13D expression. Whether the regulation of the CDK inhibitor p21 expression occurs through MAPK or PI3K signalling pathways is presently under investigation

Advances in the genetics of primary torsion dystonia

Knowledge about the genetics of primary torsion dystonia (PTD) has been progressing at a very slow pace compared with other movement disorders. For many years, only one causative gene was known, DYT1/TOR1A, yet the recent identification of a second PTD causative gene (DYT6/THAP1), the detection of subclinical alterations caused by mutations in PTD genes in some healthy non-penetrant individuals, and functional studies on TOR1A and THAP1 protein products have significantly improved mutation detection, genotype-phenotype correlates, and our understanding of the cellular mechanisms underlying the development of dystonia

Polymiss : a computer program for fitting a one- or two-factor logit-probit latent variable model to polynomous data when observations may be missing

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Some permanence results of the Dunford-Pettis and Grothendieck properties in lcHs

We prove some permanence results with respect to quotient spaces and to projective and injective tensor products of the Dunford--Pettis and Grothendieck properties in the setting of locally convex Hausdorff spaces

Differential effects of Ha-RasG12V, Ki-RasG12V and Ki-RasG13D on cell proliferation

Although differing only for the last 24 aminoacids, the three major isoforms of p21 Ras (Ha-, Ki- and N –Ras) can trigger alternative pathways of signal transduction, at least in part as a consequence of different post-translational modifications and subcellular localization. Ras mutations are a common event in tumorigenesis. In colorectal carcinomas (CRCs) the mutations affect almost exclusively Ki-Ras, while Ha-Ras mutations are mostly found in bladder carcinomas and N-Ras mutations in leukemia cells. In almost all cases, the genetic alteration is a point mutation in codons 12 or 13, and less frequently in codon 61. By affecting the GTPase activity of the protein, they always lead to a constitutively active protein. However, data obtained in different experimental systems or by analysis of primary and metastatic tumors show that mutations in different codons, different mutations in the same codon, and mutations of different isoforms of Ras may have diverse biological consequences. To shed more light on the molecular mechanisms responsible for the different effects of Ras mutations, we have obtained stable clones of HT-29 (a human colorectal adenocarcinoma cell line in which the endogenous Ras genes are wild type) transfected with cDNAs codifying Ha-RasG12V, Ki-RasG12V and Ki-RasG13D, under the control of an hormone-inducible promoter. The expression of each of these mutated Ras isoforms induces specific, different effects on cell morphology and growth rate. FACS analysis shows also a differential effect on the cell cycle. H-RasG12V expression, in addition, seems to determine apoptosis. Despite these differences, all three mutated isoforms of Ras increase the expression of the CDK inhibitor p21. Preliminary data reveal epigenetic changes in the p21 promoter region upon induction of H-RasG12V expression

Oxidative stress: new insights on the association of nonalcoholic fatty liver disease and atherosclerosis

Non-alcoholic fatty liver disease (NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to non-alcoholic steatohepatitis (NASH), which may progress to fibrosis and more severe liver complications such as cirrhosis, hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity, insulin resistance, hypertension, and dyslipidaemia, and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and, to a lesser extent, to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus, oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed, with conflicting results. In particular, vitamin E supplementation has been suggested for the treatment of non-diabetic, non-cirrhotic adults with active NASH, although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol, silybin, L-carnitine and pentoxiphylline. No trial so far, has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New, large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed

Conservative Surgical Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw with Er,Cr:YSGG Laser and Platelet-Rich Plasma: A Longitudinal Study

Abstract Introduction: The management of bisphosphonate-related osteonecrosis of the jaw (BRONJ), with no evidence-based guidelines, remains controversial. We aimed to evaluate the efficiency of a conservative surgical treatment combining Er,Cr:YSGG laser and platelet-rich plasma (PRP) for the treatment of BRONJ in cancer patients.Methods:We performed a longitudinal cohort study. Inclusion criteria were (1) age 65 18 years; (2) cancer diagnosis; (3) treatment with NBP because of the underlying cancer. Results:We consecutively recruited ten patients diagnosed with BRONJ in stage I or II. These patients underwent a surgical laser-assisted therapy together with autologous PRP. At the latest follow-up at 12 months, clinical improvement was observed in eight patients. Registration Number is IRCT20180329039159N1. Conclusion:We could successfully manage the BRONJ utilizing this combined protocol to heal the 30% of surgically treated sites and to improve the 50% of patients' lesions clinically. Our findings suggest that a surgical approach combined with Er,Cr:YSGG laser and PRP benefit cancer patients with general health issues