1,720,960 research outputs found
Levels of beta-secretase BACE and alpha-secretase ADAM10 mRNAs in Alzheimer hippocampus.
No full textInhibition of heme synthesis alters Amyloid Precursor Protein processing
No full textDecay of mitochondria, energy failure and increased oxidative stress are features commonly detected in brains from Alzheimer's disease (AD) patients. Recent findings indicate that neuronal heme deficiency may contribute to the appearance of those cytopathologies and potentially alter the course of AD. We repressed heme synthesis in cells by inhibiting ferrochelatase enzyme with small interfering RNA and N-methylprotoporphyrin IX. The treatments induced a severe perturbation of mitochondria and energy production, with decrease of the subunit II of Cytochrome c Oxidase, alteration of the membrane potential and a 50% reduction of intracellular ATP. The state and processing of the Amyloid Precursor Protein (APP) was also affected, with the appearance of APP aggregates and a significant decrease (30-40%) of sAPPα secretion, associated with perturbation of ADAM10 and TACE, enzymes involved in the α-secretase cleavage. The production of sAPPβ was increased, without augment of Amyloid β generation. Our findings strengthen the hypothesis that a reduced availability of heme may play a role in AD pathogenesis
Association analysis between anterior-pharynx defective-1 genes polymorphisms and Alzheimer's disease.
No full textPOLYMORPHISMS IN THE LOC387715/ARMS2 PUTATIVE GENE AND THE RISK FOR ALZHEIMER'S DISEASE.
No full textBackground: Age-related macular degeneration (ARMD) and Alzheimer’s disease (AD) are neurodegenerative disorders that share a high prevalence among elderly people, the extracellular deposition of amyloid beta, and the involvement of genetic factors in their aetiology. Genetic linkage with the chromosome regions 10q26 and 10q24-25 have been shown for ARMD and AD, respectively. The rs10490924 polymorphism, the major determinant of the 10q26 association with ARMD, determines the A69S substitution in the LOC387715/ARMS2 gene. Little information is available about the expression of the gene in humans. Methods: we analysed the expression of the gene by RT-PCR in the brain and we looked for nucleotide variations in the gene sequence by DHPLC. Results: We found specific gene transcripts in the hippocampus, cortex and cerebellum. The genetic analysis identified two other common variations, which determine the R3H change (rs10490923) and a premature stop codon (rs2736911), respectively. The analysis of their distribution in 213 AD patients and 149 controls revealed a trend for a reduced frequency of the variant allele of rs2736911 in AD patients (P = 0.038), with an Odds Ratio of 0.631. Conclusion: the LOC387715/ARMS2 gene is expressed in the human brain and it may concur to the individual risk for AD
DNA sequence variations in the prolyl isomerase Pin1 gene and Alzheimer's disease.
No full textSenile plaques and neurofibrillary tangles (NFT) are the prominent lesions in the brain of Alzheimer’s disease (AD) patients. NFT are mainly
composed of an abnormally phosphorylated form of tau protein, which has lost its function to bind microtubules and promote their assembly.
Tau hyperphosphorylation critically decreases tau function and precedes neurodegeneration. The majority of tau phosphorylation sites are
Ser/Thr-Pro motifs, which are known to exist in two distinct cis and trans conformations. The prolyl isomerase Pin1 catalyses the conversion
of those conformations. Pin1 binds to tau specifically at the Thr231-Pro site and restores tau function, either by inducing conformational
changes or facilitating dephosphorylation. It has been shown that Pin1 expression levels inversely correlate with the predicted vulnerability
of different brain areas to neurodegeneration and soluble Pin1 is depleted in neurons from AD brains; furthermore, Pin1 knock-out mice
develop signs and symptoms of tau-related pathologies late in life. It seems that Pin1 plays an important role in maintaining tau function,
thereby preserving neuronal homeostasis and preventing age-dependent neurodegeneration. DNA sequence variations in Pin1 gene may affect
its expression level or function and influence the individual risk for developing AD. We screened by denaturing high performance liquid
chromatography the genomic DNA of 120 AD subjects and 134 age-matched controls and we found very few and rare sequence variations
in the promoter region and in exons 2 and 3. We conclude that Pin1 is a very well conserved gene, whose rare nucleotide variations have no
effect on the individual genetic risk for AD
Frequency and role of HPV in the progression of epithelial dysplasia to oral cancer.
No full textBackground: Human papillomavirus DNA (HPV DNA) and p16 and p53 protein expressions were investigated for their role in transforming dysplasia into squamous cell carcinoma of the oral cavity in a non-smoker and non-drinker patient group. Materials and Methods: A total of 56 oral biopsies from non-smoker and non-drinker patients were analyzed. The specimens were grouped into three categories: group 1 included 31 cases of hyperplastic mucosa and mild dysplasia, group 2 included 14 cases of moderate and severe dysplasia, while group 3 comprised 11 cases of invasive squamous cell carcinomas. In all cases, immunohistochemical methods were performed to detect p16 and p53 protein expressions. The nested polymerase chain reaction for HPV (nested HPV-PCR) and the catalyzed signal-amplified colorimetric DNA in situ hybridization (CSAC-ISH) methods were applied for HPV DNA detection and typing of high-risk genotype. Results: P16 protein, absent from all specimens of group 1, was especially noted in group 2 (92.86%) and in group3 (54.55%). Five out of 14 of group 2 cases (35.71%) and 3/11 (27.27%) of group 3 were HPV DNA positive. The HPVs detected were of both high-risk and low-risk genotype. The analysis of the relationship between HPV and p16 protein expression revealed that all the group 2 and 3 samples with HPV DNA, overexpressed p16 protein. Conclusion: The results suggest that HPV could be a molecular marker in group 2 and 3 specimens in non-smoker and non-drinker patients. The virus may play an etiological role in carcinogenesis in the oral cavity. The association between HPV and p16 overexpression suggests a molecular mechanism similar to that found in cervical cancer
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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