202 resultados para Late Endosomes
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BACKGROUND: Whether or not cognitive impairment and brain structure changes are trait characteristics of late-life depression is still disputed. Previous studies led to conflicting data possibly because of the difference in the age of depression onset. In fact, several lines of evidence suggest that late-onset depression (LOD) is more frequently associated with neuropsychological deficits and brain pathology than early-onset depression (EOD). To date, no study explored concomitantly the cognitive profile and brain magnetic resonance imaging (MRI) patterns in euthymic EOD and LOD patients. METHOD: Using a cross-sectional design, 41 remitted outpatients (30 with EOD and 11 with LOD) were compared to 30 healthy controls. Neuropsychological evaluation concerned working memory, episodic memory, processing speed, naming capacity and executive functions. Volumetric estimates of the amygdala, hippocampus, entorhinal and anterior cingulate cortex were obtained using both voxel-based and region of interest morphometric methods. White matter hyperintensities were assessed semiquantitatively. RESULTS: Both cognitive performance and brain volumes were preserved in euthymic EOD patients whereas LOD patients showed a significant reduction of episodic memory capacity and a higher rate of periventricular hyperintensities compared to both controls and EOD patients. CONCLUSION: Our results support the dissociation between EOD thought to be mainly related to psychosocial factors and LOD that is characterized by increasing vascular burden and episodic memory decline.
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ABSTRACT: The Late Oligocene first occurrence of Miogypsina gunteri Cole and Miogypsina tani Drooger is verified in the light of larger foraminiferal assemblages from Nosara (Nicoya Peninsula, Costa Rica) and Windward (Carriacou, Grenada, Lesser Antilles). At Windward, they co-occur with planktonic foraminifera and nannofossils studied by earlier workers. 87Sr/86Sr isotope ratios were measured in calcite of larger foraminifera at both sites to determine independent absolute ages of the two outcrops. Late Oligocene shallow water formations unconformably overlie Paleocene-Eocene distal turbidites and siliceous shales in the outcrops in Costa Rica. The shallow-water lithostratigraphy includes near shore volcanic sandstones that alternate with sandy bioclastic limestones. The latter have yielded rich assemblages of larger foraminifera that have been studied in oriented sections, SEM for split material and polished rock thin sections for transmitted light and cathodoluminescence (CL) observation. The association of larger foraminifera includes Heterostegina antillea Cushman, Miogypsina tani Drooger, Miogypsina gunteri Cole, Miogypsina c.f (Miolepidocyclina) panamensis (Cushman), Miogypsina sp., Lepidocyclina (nephrolepidina) vaughani Cushman, Lepidocyclina yurnagurensis Cushman, Lepidocyclina undosa Cushman. At Windward, scattered outcrops of the Belvedere Formation expose mass flow deposits rich in larger foraminifera associated with an early late Oligocene (NP24) planktonic foraminifa assemblage. Planktonic foraminifera and nanno-fossils recovered in rocks slightly downsection indicate an upper Middle Oligocene age. Larger foraminifera species collected just north of Windward include Lepidocyclina undosa Cushman and Miogypsina gunteri Cole. The 87Sr/86Sr ratio was measured in 11 specimens of megalosphaeric Lepidocyclina spp., mechanically extracted from 2 rock samples collected at Punta Peladas (Costa Rica) Ratios range from 0.709088 to 0.708196, which correspond to a model age of 27.4 to 24.94 Ma. Very similar ratios, ranging from 0.708150 to 0.708167 were obtained from Windward Village (Carriacou). All measured 87Sr/86Sr ratios fall within a Chattian (Late Oligocene) age. Nannofossils, planktonic foraminifera and identical 87Sr/86Sr ratios from Punta Peladas and Windward clearly indicate a Chattian (Upper Oligocene) first occurrence of Miogypsina gunteri and Miogypsina tani and confirm this age range for the other larger foraminifera cited above. The first occurrence of Miogypsina gunteri in the lower Athe upper Aquitanian as proposed by European workers cannot be confirmed.
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Thyroid hormone receptors (TRs) are members of the nuclear hormone receptor superfamily, which act as transcription factors upon binding to specific DNA sequences called thyroid hormone (T3) response elements (TREs). Such elements are found in the upstream regulatory region of promoters as well as in intragenic sequences of T3-responsive genes. In this report, we demonstrate that SV40 late (SVL) promoter activity is strongly down-regulated by TR in the absence of ligand. Addition of T3 releases this repression, but does not further induce SVL promoter activity. Electrophoretic mobility shift analyses reveal a TR binding element that overlaps with the SV40 major late transcription initiation site. This element closely fits the consensus TRE, formed of two hexanucleotides organized in a tandem repeat separated by 4 nt, and is able to confer T3 responsiveness on a heterologous promoter. We further show that, although the presence of TR leads to quantitatively modified expression of an SVL-driven reporter gene, neither displacement of the site of transcription initiation nor modification of the splicing pattern of the primary transcripts occur.
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Pour connaître le devenir à long terme des patients intubés pour état de mal asthmatique, nous avons recontacté en 1990 les 34 patients qui avaient présenté, entre 1978 et 1988, quarante épisodes de détresse respiratoire aiguë. Deux patients sont vivants mais ont été perdus de vue, 3 sont morts dont un seul d'état de mal asthmatique 6 mois après l'épisode initial. Des 29 patients restants (7 hommes et 22 femmes, âge moyen de 48,5 ans) représentant un suivi moyen de 9,6 ans, quinze n'ont jamais été réhospitalisés; des 14 autres, seuls 5 ont requis une intubation et une ventilation mécanique lors d'un épiode ultérieur. La majorité des hospitalisations ultérieures (81%) sont survenues dans les 6 ans suivant l'épiode initial
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Conjunctival nevi are lesions observed commonly occasionnally and can be found later in a life. Such a lesion was observed on the conjunctival semilunar fold in a 76-year-old female patient. It was oval in shape, pigmented, and was mainly visible when the affected eye was in abduction. As no accurate anterior clinical history was available, surgical resection was performed. Hitopathological study disclosed a subepithelial nevus, which was completely resected. Regular follow-up was recommended, as is usual after surgical resection of a conjunctival pigmented tumor.
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The identification of genetic causes for Mendelian disorders has been based on the collection of multi-incident families, linkage analysis, and sequencing of genes in candidate intervals. This study describes the application of next-generation sequencing technologies to a Swiss kindred presenting with autosomal-dominant, late-onset Parkinson disease (PD). The family has tremor-predominant dopa-responsive parkinsonism with a mean onset of 50.6 ± 7.3 years. Exome analysis suggests that an aspartic-acid-to-asparagine mutation within vacuolar protein sorting 35 (VPS35 c.1858G>A; p.Asp620Asn) is the genetic determinant of disease. VPS35 is a central component of the retromer cargo-recognition complex, is critical for endosome-trans-golgi trafficking and membrane-protein recycling, and is evolutionarily highly conserved. VPS35 c.1858G>A was found in all affected members of the Swiss kindred and in three more families and one patient with sporadic PD, but it was not observed in 3,309 controls. Further sequencing of familial affected probands revealed only one other missense variant, VPS35 c.946C>T; (p.Pro316Ser), in a pedigree with one unaffected and two affected carriers, and thus the pathogenicity of this mutation remains uncertain. Retromer-mediated sorting and transport is best characterized for acid hydrolase receptors. However, the complex has many types of cargo and is involved in a diverse array of biologic pathways from developmental Wnt signaling to lysosome biogenesis. Our study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.
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A new genus (Triassiphaeodina gen. nov.) and two new species (Medusetta japonica sp. nov. and Triassiphaeodina niyodoensis sp. nov.) of Late Triassic (Rhaetian) phaeodarian Radiolaria are described from a phosphatic nodule found in melange rocks of the Northern Chichibu Belt, Shikoku, Japan. The Rhaetian age of the nodule and of the phaeodarian new taxa is based on co-occurring Polycystina Radiolaria, including Bipedis acrostylus Bragin, Livarella densiporata Kozur and Mostler, Fontinella primitiva Carter, and Ferresium sp. A of Carter (1993). This finding shows that phaeodarian Radiolaria were already represented in Late Triassic oceans, with morphologies similar to those known in the Late Cretaceous and Cenozoic, from which they have previously been reported. The new taxa described herein represent the oldest known phaeodarian fossils.
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Mycoplasma hominis and Ureaplasma spp. may colonize the human genital tract and have been associated with adverse pregnancy outcomes such as preterm labour and preterm premature rupture of membranes. However, as these bacteria can reside in the normal vaginal flora, there are controversies regarding their true role during pregnancy and so the need to treat these organisms. We therefore conducted a retrospective analysis to evaluate the treatment of genital mycoplasma in 5377 pregnant patients showing symptoms of potential obstetric complications at 25-37 weeks of gestation. Women presenting with symptoms were routinely screened by culture for the presence of these bacteria and treated with clindamycin when positive. Compared with uninfected untreated patients, women treated for genital mycoplasma demonstrated lower rates of premature labour. Indeed preterm birth rates were, respectively, 40.9% and 37.7% in women colonized with Ureaplasma spp. and M. hominis, compared with 44.1% in uncolonized women (Ureaplasma spp., p 0.024; M. hominis, p 0.001). Moreover, a reduction of neonatal complications rates was observed, with 10.9% of newborns developing respiratory diseases in case of Ureaplasma spp. colonization and 5.9% in the presence of M. hominis, compared with 12.8% in the absence of those bacteria (Ureaplasma spp., p 0.050; M. hominis, p <0.001). Microbiological screening of Ureaplasma spp. and/or M. hominis and pre-emptive antibiotic therapy of symptomatic pregnant women in late pregnancy might represent a beneficial strategy to reduce premature labour and neonatal complications.
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Objective: The incidence of late-onset cytomegalovirus disease (i.e. disease appearing after discontinuation of antiviral prophylaxis) in solid-organ transplant recipients remains excessively high. This review will focus on describing the several strategies that could potentially reduce the incidence of late-onset cytomegalovirus disease. Methods: We reviewed the literature and presented our own clinical experience in the field. Results: The incidence of late-onset cytomegalovirus disease in recent trials can be as high as 36% in high-risk patients (donor positive/recipient negative for cytomegalovirus). The extension of antiviral prophylaxis to six months has recently proven in a prospective randomized controlled trial to be effective for reducing late-onset cytomegalovirus disease. The monitoring of cytomegalovirus viral load by PCR after the discontinuation of prophylaxis seems to be of moderate usefulness in low/intermediate-risk patients. The use of low-dose valganciclovir could reduce drug toxicity and costs while maintaining similar efficacy, but further studies are needed. A potentially interesting approach to predict the individual risk for development of cytomegalovirus disease appears to be the assessment of specific cell-mediated immune response. If cell-mediated immunity assays become widely available in transplant centers in the future, these assays may possibly be used to tailor the cytomegalovirus preventive strategy on an individual basis. Finally, recent prospective trials have evaluated novel cytomegalovirus vaccines that merit further evaluation in the transplant setting, although currently there is no cytomegalovirus vaccine that has been approved for routine clinical use. Conclusions: Several studies have recently evaluated novel strategies to reduce the incidence of late-onset cytomegalovirus disease. It is therefore expected that this improvement in preventive strategies will allow to further reduce the negative effects of cytomegalovirus disease after transplantation.