8 research outputs found
[Folder 01]: PrEP 1519
No full textO PrEP 1519 é um projeto de pesquisa que tem como objetivo a prevenção do HIV/AIDS entre adolescentes de 15 a 19 anos
[Folder 03]: PrEP 1519
No full textO PrEP 1519 é um projeto de pesquisa que tem como objetivo a prevenção do HIV/AIDS entre adolescentes de 15 a 19 anos
[Recomendações para gestão do processo de trabalho nos serviços de saúde]
No full textAs recomendações em relação à gestão do processo de trabalho nos serviços de Profilaxia Pré-Exposição para Adolescentes (PrEP)
Chauliopleona armata
No full textChauliopleona armata (Hansen 1913) (Figures 1B–G, 5–7, 18) Leptognathia armata Hansen, 1913: 80–81, pl. VIII figs. 1a–f Leptognathia armata: Nierstrasz 1913: 30; Stephensen 1932: 347; Stephensen 1943: 36, 63; Holdich and Bird 1985: 443 table 1; else, see Sieg 1983 Chauliopleona armata: Guerrero-Kommritz 2005: 1188–1191, figs. 5–6; else, see Anderson 2013 Diagnosis Cephalothorax 1.3–1.6 times ltb. Pereonites all shorter than broad; with parallel lateral margins. Pleon shorter than cephalothorax, without posteriodorsal protuberance; pleonites 1–4 sternite with subtriangular sternal process. Antennule article-1 (1.2 times) longer than rest of antennule. Maxilliped basis with long seta. Cheliped merus without inferior protuberance; carpus fairly stout, 1.6 times ltb, inferior shield shallow (aspect ratio ≈ 0.3), rounded, distal margin not angular; fixed finger with four teeth; dactylus superior margin smooth. Pereopods 1–3 basis margins smooth; propodus inferior spinules numerous, moderate or robust. Pereopods 2–3 carpus without distomedial seta. 1 Pereopods 4–6 ischium with two short setae. Uropod exopod about half as long as endopod segment-1; endopod> three times longer than peduncle. Material examined BIOICE stns. One non-ov. ♀, 2810; 21 non-ov. ♀♀ (one dissected on microslide), 18 prep. ♂♂, 2856; one non-ov. ♀, one prep. ♂, 2859; six non-ov. ♀♀, one ov. ♀, two prep. ♂♂, 2860; one non-ov. ♀, one prep. ♂, 2863; one prep. ♂, 3067; one prep. ♂, 3071; one non-ov. ♀, 3504; one non-ov. ♀, 3515. AFEN Stn. One individual, 54591#1; one non-ov. ♀, 54600#2. Co-type. Non-ov. ♀, Ingolf Stn 22. Other material. SMBA stns: one individual (ind.), ES105; four ind., ES218; two ind., SBC61; two ind., one ind., SBC68; SBC166; one ind., SBC216. INCAL stns: one ind., CP01; two ind., CP02; one ind., DS01. Size Non-ovigerous female. Body length 2.28–3.64 mm, cf. 3.6 mm as measured by Hansen (1913) or 3.8 mm by Guerrero-Kommritz (2005). Ovigerous female: body length 2.96 mm. Preparatory male. Body length 2.72–3.44 mm, cf. 3.3 mm Hansen (1913). Distribution records from the AFEN, BIOICE and BIOFAR area Eleven from AFEN: two from North Feni Ridge, 1600–2000 m, eight from the northern Rockall Trough, 1859–1871 m, and one from the Hebrides Slope, 1800 m. Ten records from BIOICE: all from the Iceland Basin, 1333–2400 m; with positive bottom temperatures 2.1–3.99°C and a variety of sediment types including ‘silty sand’, ‘shell debris’, ‘silt’ and ‘muddy gravel’. Distribution elsewhere The type locality is the Davis Strait, 2702 m, and southwest of Cape Farewell, 3474 m (Hansen 1913). I have 51 records from the northeast Atlantic, extending from the Iceland Basin (deeper and further south than the BIOICE area) to the southern Bay of Biscay, including the South Feni Ridge, Rockall Trough, Porcupine Seabight, Celtic and Armorican Slopes, and Biscay Abyssal Plain, 1180–4823 m (SMBA, IOS, COB, Chain-106). Some of these were reported by Holdich and Bird (1985). These data are available from the author on request. Remarks A significant problem in assessing any new records of C. armata is that the original type material consists of only two specimens (Figure 1B–G) and this shows some differences from the specimens illustrated here that have a slightly shorter cephalothorax and somewhat weaker propodal spinules on pereopods 1–3 (Figure 7A–C). If these new records are genuine, Chauliopleona armata appears to be a eurybathic species, inhabiting both bathyal (200–2000 m) and abyssal zones (2000–6000 m). However, it is almost certain that the records of C. armata outside of the Atlantic Margin study area (see above) refer to more than one species, and the material needs re-examination.Published as part of Bird, Graham John, 2015, Tanaidacea (Crustacea: Peracarida) of the northeast Atlantic: Chauliopleona Dojiri and Sieg, 1997 and Saurotipleona n. gen. from the ' Atlantic Margin', pp. 1507-1547 in Journal of Natural History 49 (25) on pages 1519-1524, DOI: 10.1080/00222933.2015.1005715, http://zenodo.org/record/399969
Identification of novel genetic and prognostic markers in hereditary and sporadic cancer: "two sides of the same coin"
No full textThis thesis has focused on the discovery and characterization of novel diagnostic and prognostic markers in various cancer entities, with a special emphasis on colorectal cancer (CRC).
In Switzerland the incidence of colorectal cancer ranks third in males and second in females, with about 4000 new patients diagnosed each year. Incidence trends over the last decades have remained constant in both sexes, whereas mortality rates have been decreasing. Decreasing mortality is thought to be related to improved treatment during the past years as well as generalisation of colorectal cancer screening in the Swiss population. About 80% of colorectal cancers are thought to have occurred by chance (sporadic) with the remainder displaying either familial aggregation (about 15%) or mendelian inheritance (about 5%).
In the first part of this work we identify and characterize a novel target gene locus for microsatellite instability (MSI) consisting of a mononucleotide (T/U)16 tract, EWS16T, located in the 3’ UTR of the Ewing sarcoma break point region 1 (EWSR1) gene in 319 patients with hereditary and sporadic CRC. We show that the EWS16T locus discriminates MMR proficient from deficient cancers with high diagnostic sensitivity (100%) and specificity (100%). It could thus substantially improve and facilitate MSI analysis in routine daily practice. In addition, biochemical analyses indicate that EWS16T contractions alter poly(A) site selection by promoting SFPQ-mediated distal poly(A) site usage in EWSR1 pre-mRNAs and result in decreased mRNA as well as EWS protein expression. Our findings thus directly implicate the RNA-/DNA-binding Ewing sarcoma protein in MSI-associated colorectal tumorigenesis.
In the second part we characterize a new tumour suppressor gene designated SH2D4A located on the short arm of chromosome 8. We demonstrate that SH2D4A physically interacts with the EGFR/STAT3 pathway and controls cell proliferation. Upon EGF signaling, SH2D4A recruits the serine/threonine phosphatase PP1β to the receptor complex and represses activated STAT3 via dephosphorylation. SH2D4A expression reduces anchorage-independent tumour cell growth and its loss promotes the expression of c-Myc, Cyclin D1 and Jun B. In addition we show that SH2D4A expression is partially lost in human colorectal cancers as a result of chromosomal instability, mutations and epigenetic changes. Finally, diminished SH2D4A protein expression was found to correlate with advanced disease stages and was associated with poor prognosis.
In the third part we investigate HGMA1/HGM2 protein expression 210 and 1202 patients with pancreatic and breast cancers, respectively. HMGA1 and HMGA2 over-expression was found in a significant number of breast and pancreatic carcinoma samples, and its over-expression positively correlated with grade and stage of the disease. Conversely, no HMGA1 and HMGA2 expression was observed in cancer-free breast and pancreas tissues. Taken together, our findings show that high expression levels of HMGA1 and HMGA2 are related to an unfavorable histological type and a poor prognosis in both, pancreatic and breast cancer. Moreover, these findings further support the notion that these proteins represent appropriate targets for the therapy of human cancer, as suggested by numerous in vitro and in vivo studies.
In the fourth part of the thesis we evaluate the potential role of the cancer stem cell (CSC) proteins EpCAM, CD44s, CD166 and CD133 in tumors of the ampulla of Vater. CSC expression was determined in 175 carcinoma, 111 adenoma and 152 cancer free-mucosa specimens arranged on a tissue microarray format. The expression of all evaluated marker proteins differed significantly between cancer-free mucosa, adenoma and carcinoma samples. EpCAM expression was significantly correlated with better patient survival. In contrast, increased expression of CD44s, CD166 and CD133 from normal mucosa samples to adenoma and carcinoma was linked to tumor progression but no statistically significant correlation with survival observed. Our findings therefore indicate that in ampullary carcinomas loss of EpCAM expression may be associated with a more aggressive tumor phenotype.
In the fifth part we develop a specific monoclonal antibody for the highly immunogenic member of the MAGE-A family of cancer/testis tumor-associated antigens (C/T TAAs). The antibody was used to stain a multi-tumor tissue microarray comprising more than 2,500 paraffin-embedded specimens of different histological origin. C/T TAA appears to be expressed in a high percentage (>50%) of cancer cells from different tumor types such as lung, skin, gynecological, stomach and gall bladder cancers. The future characterization of MAGE-A10-specific antibodies might set the stage for the development of targeted active immunotherapy by clarifying potential indications and by allowing the selection of patients eligible for treatment and monitoring of its effectiveness
The organizational and structural dimensions of hunter-gatherer lithic technology : theoretical perspectives from ethnography and ethnoarchaeology applied to the Mesolithic of mainland Britain with a case study from northern England.
No full textThe organizational (procurement, manufacture, maintenance/discard) and structural (composition, diversity, complexity) dimensions of contemporary hunter-gatherer technological strategies are discussed in terms of the selective advantages for limiting subsistence costs and/or risks. It is argued that where subsistence is primarily cost (energy) limited technological strategies differ from those employed where risk (time) is limiting. Anticipatory organizational strategies - embedded procurement and reduction, and curation - achieve their most significant role in time-stressed contexts where there are selective benefits in separating subsistence and technological schedules. Structural strategies-- function-specific tools, diverse tool-kits, complex tool design - offer selective benefits where the act of food procurement is time-stressed. If subsistence is time-stressed but cannot be effectively 'separated from technological schedules tools may be made both reliable (high component redundancy) and maintainable (readily repaired) - the latter being facilitated by limiting component design thereby enabling materials of varied quality to be employed. The implications of differing organizational and structural strategies for the formation of the archaeological record and for the lithic analyst are discussed. Evidence concerning the environment, chronology, economy, settlement and technology of the Mesolithic of mainland Britain is reviewed. For the Earlier Mesolithic an alternative to the Clark model of subsistence and mobility is developed, whilst multivariate analyses of stone tool inventories and evidence concerning the function, complexity and design of microlithic tools provides the basis for suggestions as to the character and significance of the Earlier-Later Mesolithic transition. Analyses of lithic debitage from sites in northern England provide evidence for embedded procurement and reduction strategies during the Earlier Mesolithic consistent with the expectations of a model where autumn was spent in upland valleys engaged in intercept hunting, winter was spent in lowland residences
Conditional strategies to study gene function during gonadal development in mammals.
No full textSexual development in mammals involves a complex cascade of genetic events. These begin with a cell fate decision, whether to make Sertoli or follicle cells, that gives rise to the development of a male or female gonad, which is controlled by the testis-determining gene Sry. Following the expression of Sry, genes involved in the male pathway act to reinforce and maintain testis-specific cell fate decisions, as well as to repress the female pathway. Sox9 becomes rapidly upregulated after the onset of Sry expression, and is expressed in Sertoli cells throughout life. From mutation studies, SOX9 is known to be essential for male development in humans and to initiate Sertoli cell differentiation in mice. However, the function of SOX9 after sex determination and the reason for its maintenance in Sertoli cells remains unknown. In order to understand the function of Sox9 in the fetal and adult mouse testis, new tools have been generated to control gene activity in a conditional manner. This thesis mainly describes strategies to control either deletion of misexpression of Sox9. To make the tools useful at different stages, the tamoxifen-inducible Cre/loxP system was employed. This involves the establishment of two elements: a "Cre-driver" and a ' Sox9-responder". Cre-driver transgenes were made under the control of several gonadal-specific regulatory elements, as well as a strong, ubiquitous promoter. Responder mice allow Cre activated conditional misexpression or deletion of Sox9. Analyses on gonad morphologies and gene expression levels were compared between animals that have altered Sox9 expression and those that have not. The results reveal that Sox9 is necessary and sufficient for the expression of Sfl in the Sertoli cells, and suggest that Sox9 is antagonistic to the ovarian- specific gene Foxl2. The newly established Cre-drivers can also be applied in functional studies involving other genes implicated in sexual development
Innovative approaches to monitor mutant huntingtin and to facilitate its degradation in Huntington's disease models
No full textHuntington’s disease (HD) is a dominant genetic neurodegenerative disease caused by a mutation in the exon 1 of the huntingtin gene. The clinical symptoms, such as motor disturbances (chorea), cognitive decline and psychiatric impairments are usually developed by the patients in mid-life. Mutant huntingtin protein presents an amplification of a polyglutamine repeat at its N-terminus, which induces conformational changes and leads to neurotoxicity, impairment of cell homeostasis and neuronal cell death. The neuropathology of HD is characterized by a progressive degeneration of the brain starting from the striatum and spreading to other regions such as cortex, hypothalamus and cerebellum. In addition to the diffused brain atrophy, HD patients are also affected by multiple peripheral symptoms which contribute to worsening disease progression and eventually lead to death approximately two decades after onset.
The mechanisms leading to the toxicity induced by mutant huntingtin are not well understood. However the acquisition of a misfolded conformation and the formation of intracellular inclusions constituted by shorter fragments of the mutant protein are considered important in the neurodegenerative process.
In my thesis project I have investigated mechanisms to enhance the cellular degradation of mutant huntingtin. A second focus was on the development of an immunoassay to detect and quantify aggregates in HD models.
I analyzed the data obtained form a high through-put screen aimed to identify small molecular weight compounds decreasing mutant huntingtin levels in cells. Among all compounds screened, only inhibitors of heat shock protein 90 (Hsp90) showed a significant effect on mutant huntingtin clearance. I therefore investigated the mechanisms of Hsp90 chaperone inhibition and the reduction of soluble mutant huntigtin levels. Data from biochemical assays demonstrated that mutant huntingtin degradation is enhanced upon compound treatment and that the protein is cleared through the ubiquitin-proteasome system. This was independent from the heat shock response induced after pharmacological Hsp90 inhibition. Co-immunoprecipitation experiments suggested that mutant huntingtin is a client protein of Hsp90. The results were replicated in different cellular models including full length mutant huntingtin expressed from the endogenous locus, thus highlighting the importance of Hsp90 in stabilizing soluble mutant huntingtin and suggesting the possible application of Hsp90 inhibitors as therapies in HD.
In the second project I developed a sensitive method to detect mutant protein aggregates in HD models. To this purpose I implemented the already established time resolved fluorescence resonance energy transfer (TR-FRET) based immunoassay for the detection of soluble mutant and wild-type huntingtin. A mixture of either donor or acceptor fluorophore labeled single monoclonal antibody directed against an epitope exposed on the huntingtin aggregate surface was used. This strategy allowed for energy transfer and therefore a measurable TR-FRET signal, only in presence of mutant aggregated protein. I could demonstrate the sensitivity of the bioassay on a microtiter set up both as a single assay and in a duplex combination with the previously developed TR-FRET assay for soluble huntingtin.
I applied the TR-FRET for aggregated huntingtin to samples from R6/2 and HdhQ150 mice, expressing exon 1 and full length mutant huntingtin, respectively. In brain homogenates from both models there was an age-dependent, inverse correlation between soluble and aggregated mutant huntingtin. These findings supported the importance of the relation between aggregated and soluble protein in disease progression. Furthermore, I detected the inverse correlation also in peripheral tissues of R6/2 mice where the presence of aggregates was previously demonstrated with other methods. An in-depth analysis of R6/2 samples in a combination of TR-FRET and size exclusion chromatography suggested a differential specificity of the two antibody combinations used for different aggregate populations. The TR-FRET method provides a new means to characterize the aggregation process as well as to test the efficacy of possible disease modifying treatments for HD
