Aortic stiffness underlies systolic hypertension, promotes heart failure and is associated with increased cardiovascular morbidity and mortality. It is regarded as a primary driver of left ventricular hypertrophy and aortic aneurysms and is linked to the pathogenesis of cognitive impairment, stroke and renal failure. Like most cardiovascular traits, aortic stiffness is a complex trait and is moderately heritable, yet the precise molecular mechanisms that underpin the stiffening process remain poorly defined. This study aimed to employ multiple approaches to further identify the genetic basis of aortic stiffness in a large repository of human donor aortas that had undergone ex vivo pulse wave velocity (PWV) phenotyping. The first part of this work sought to investigate the molecular basis of Loeys-Dietz type 4 syndrome in a pedigree with multiple cases of aortic aneurysms and dissections. A missense variant p.(Arg320Cys) was identified in a highly evolutionary conserved region of TGFB2. There was striking upregulation of TGFB1, TGFB2 and pSMAD2/3 on imunocytochemical straining and western blotting of the aortic tissue from the index case confirming the functional importance of the variant. This case highlighted the striking paradox of predicted loss-of-function mutations in TGFB2 causing enhanced TGFβ signalling in this emerging familial aortopathy and underscored the significance of TGFβ signalling in aortic extracellular matrix biology. The second part of this work attempted to characterise the biological basis for the susceptibility locus identified in the most recent genome wide analysis of carotid-femoral PWV. While the locus lies within the 14q32.2 gene desert, it contains regulatory elements, with the transcriptional regulator B-cell CLL/lymphoma 11B (BCL11B) and non-coding RNA DB129663 representing potential targets for these enhancers. The association of five lead SNPs from the genome-wide association studies (GWAS) meta-analysis was examined for ex vivo aortic stiffness and BCL11B and DB129663 aortic mRNA expression. Three of the five SNPs associated significantly with PWV and showed allele-specific differences in BCL11B mRNA. The risk alleles associated with lower BCL11B suggesting a protective role for BCL11B. Despite the strong association, BCL11B protein was not detected in the human aorta; however, qPCR for CD markers showed that BCL11B transcript correlated strongly with markers for activated lymphocytes. In contrast, DB129663 transcripts were detected in 55% of the samples, and of the five SNPs only one showed allele-specific differences in aortic DB129663 transcripts. No significant differences were observed in PWV between samples expressing or lack- ing DB129663, and therefore the implication of this lncRNA in aortic stiffness remains elusive. The BCL11B transcript detected in the human aorta may reflect lymphocyte infiltration, suggesting that immune mechanisms contribute to the observed association with PWV. For the final part of this work genetic associations with aortic stiffness were explored in a candidate gene-based study utilising tagging SNPs to effectively capture the genetic information from linkage disequilibrium blocks. Association analyses were performed in young, healthy ENIGMA study par- ticipants selected for high and low PWV values then validated in the remaining ENIGMA cohorts. The association of four lead SNPs was then examined for ex vivo aortic stiffness in human donor aortas. The tissue expression of these SNPs and their encoded proteins was also explored. Neither the aggrecan nor the fibulin-1 SNPs showed significant associations with ex vivo PWV in the donor aortas. The exonic aggrecan tagSNP rs2882676 displayed differential transcript abundance between homozygous allele carriers but this did not translate at the protein level. Both aggrecan and fibulin-1 were found in the aortic wall, but with marked differences in the distribution and glycosylation of aggrecan, reflecting loss of chondroitin-sulphate binding domains. These differences were age-dependent but the striking finding was the acceleration of this process in stiff versus elastic young aortas. These findings suggest that aggrecan and fibulin-1 have critical roles in determining the biomechanics of the aorta and their modification with age could underpin age-related aortic stiffening.

Submitted by Reginaldo Soares de Freitas (reginaldo.freitas@ufv.br) on 2016-06-14T09:46:30Z No. of bitstreams: 1 texto completo.pdf: 930284 bytes, checksum: c53f457fa4116be5bc4e687ad459a112 (MD5) / Made available in DSpace on 2016-06-14T09:46:30Z (GMT). No. of bitstreams: 1 texto completo.pdf: 930284 bytes, checksum: c53f457fa4116be5bc4e687ad459a112 (MD5) Previous issue date: 2002-04-16 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / O vírus do endurecimento dos frutos do maracujazeiro (PWV) é membro da família Potyviridae, gênero Potyvirus. No Brasil a doença está presente relatada nos principais Estados produtores. Plantas de maracujá-amarelo (Passiflora edulis f. flavicarpa Degener) transformadas com uma construção não traduzível correspondente a 2/3 da região 3 do gene nib e 1/3 da região 5 do gene cp de PWV-isolado Minas Gerais (PWV-MG) foram propagadas por estaquia e desafiadas por inoculação mecânica via extrato foliar tamponado com os isolados PWV-MG e PWV-isolado Pernambuco (PWV-PE). O transformante (T10) foi resistente ao PWV-MG, mas suscetível ao PWV-PE. A ausência de vírus nestes transformantes foi confirmada por ELISA indireta. As demais plantas transgênicas desenvolveram sintomas evidentes quando inoculadas com ambos os isolados. Análises de expressão gênica por hibridização demonstraram que na linhagem T10 não ocorreu acúmulo de mRNA transgênico antes da inoculação. Após a inoculação, apenas em plantas inoculadas com o isolado PWV-PE foi detectado RNA viral. Estes resultados comprovam que o transformante T10 é resistente ao isolado PWV-MG, que o mecanismo de resistência envolvido é o silenciamento gênico pós- transcricional e que este mecanismo já está ativado nas plantas transgênicas antes da inoculação com o vírus. A linhagem T10 será propagada vegetativamente a testada para resistência ao PWV em condições naturais. / The passionfruit woodiness virus (PWV) is a member of the family Potyviridae, gender Potyvirus. In Brazil the disease is present in the principal States producers. Passionfruit yellow plants (Passiflora edulis f. flavicarpa Degener) were transformed with a non translatable construction corresponding to 2/3 of the area 3 ' of the gene nib and 1/3 of the 5 ' of the gene PWV-isolated cp Minas Gerais (PWV-MG). Trangenic plants were cloned by stem cuttings and challenged by sap inoculation with isolated PWV-MG and PWV-isolated Pernambuco (PWV-PE). The transgenic plant (T10) was resistant to PWV-MG, but susceptible to the PWV-PE. The virus absence in these plant was confirmed by ELISA indirect. The other transgenic plants developed evident symptoms when inoculated with both isolated ones. Northern blot analyses demonstrated that in the transgenic plant T10 did not accumulate transgenic mRNA before the inoculation. After the inoculation, viral RNA was detected just in plants inoculated with the isolated PWV-PE. These results proved that the transgenic plant T10 was resistant to isolated PWV-MG, that the resistance mechanism involved it was post-transcriptionaly gene silencing and that this mechanism was already activated in the transgenic plants before virus inoculation. The transgenic plant T10 will be vegetatively propagated and tested for resistance to PWV under natural conditions. / Não foi encontrado o currículo lattes do autor.

No description available.

This thesis deals with the methodology of use of whole-body impedance cardiography for evaluation of pulse wave velocity. The first three chapters explain selected hemodynamic properties of the arterial system related to the issue of pulse wave propagation. At the same time the ordinary methods for estimation, its disadvantages and merits has been summarized. Points at issue of whole-body impedance evaluation methodology for pulse wave velocity are researched in second part of this thesis. In order that analysis the procedure for correct methodology has been determined. Particularly determination of reference proximal point for calculation of transit time towards aortic valve, and design and accuracy of transit distance measurement were discussed. Based on the obtained data, a calculation of representative pulse wave velocity to eight limb locations was performed.

<p>The aim of the work was to investigate the possibility to combine information from PPG and bio-acoustic technology to extract information that is related to the blood pressure. The measurements have been carried out with several different configurations. First the relation between arterial sounds and the PPG-signal was studied. After those measurements with both PPG and the bio- acoustic technique was concluded on people in different positions and after riding a bike. The goal was to vary the blood pressure. The conclusion that can be drawn in this report is that the bio-acoustic and the PPG-signal in peripheral arteries have the same source. That implies that arterial sounds are a product of turbulence when the pulse wave passes by. Further it can be assumed that it is the first heart sound that is represented in the arterial sounds. The time before and after the arterial sound in one heart cycle vary whit the blood pressure. There relationship seems also to vary with the bloodpressure but it vary differently under different conditions.</p>

The aim of the work was to investigate the possibility to combine information from PPG and bio-acoustic technology to extract information that is related to the blood pressure. The measurements have been carried out with several different configurations. First the relation between arterial sounds and the PPG-signal was studied. After those measurements with both PPG and the bio- acoustic technique was concluded on people in different positions and after riding a bike. The goal was to vary the blood pressure. The conclusion that can be drawn in this report is that the bio-acoustic and the PPG-signal in peripheral arteries have the same source. That implies that arterial sounds are a product of turbulence when the pulse wave passes by. Further it can be assumed that it is the first heart sound that is represented in the arterial sounds. The time before and after the arterial sound in one heart cycle vary whit the blood pressure. There relationship seems also to vary with the bloodpressure but it vary differently under different conditions.

Submitted by Naira Barbosa (nairacsb@gmail.com) on 2016-04-06T19:43:23Z No. of bitstreams: 1 Anatomia foliar e diversidade genética (Dissertação) 2016.pdf: 1843568 bytes, checksum: 913521d732501d52121efcc41937185f (MD5) / Approved for entry into archive by Alda Lima da Silva (sivalda@ufba.br) on 2016-04-06T21:17:35Z (GMT) No. of bitstreams: 1 Anatomia foliar e diversidade genética (Dissertação) 2016.pdf: 1843568 bytes, checksum: 913521d732501d52121efcc41937185f (MD5) / Made available in DSpace on 2016-04-06T21:17:35Z (GMT). No. of bitstreams: 1 Anatomia foliar e diversidade genética (Dissertação) 2016.pdf: 1843568 bytes, checksum: 913521d732501d52121efcc41937185f (MD5) / CAPES, Fapesb, Embrapa Mandioca e Fruticultura. / O maracujá, Passiflora sp., possui grande importância econômica no Brasil, sendo o país o principal produtor mundial da fruta e importante centro de diversidade do gênero. As pragas são os principais problemas que afetam a cultura, e dentre estas destaca-se o endurecimento do fruto, causada, principalmente, pelo Cowpea aphid-borne mosaic virus, CABMV. Ainda não se conhece uma medida de controle efetiva para esta doença, de forma que são imprescindíveis técnicas alternativas para seu controle e manejo. Neste contexto, o melhoramento genético do maracujazeiro pode ser realizado a partir de espécies silvestres resistentes a pragas. Este trabalho teve como objetivos: a) avaliar as alterações anatômicas decorrentes da infecção com o CABMV em cinco espécies de Passiflora (P. edulis f. flavicarpa, P cincinnata, P. gibertii, P. maliformis e P. setacea) e b) avaliar a diversidade genética em populações da espécie com menores alterações anatômicas decorrentes da infecção. Para a avaliação anatômica foi estabelecido um ensaio biológico, constituído de seis plantas de cada espécie, das quais a metade foi inoculada mecanicamente com um isolado do CABMV e a outra metade inoculada somente com tampão de inoculação. Após 60 dias da inoculação, foram coletadas, como amostras, a quinta folha, do ápice para a base, de cada planta. As amostras foram fixadas em FAA e posteriormente conservadas em etanol 70%, posteriormente foram realizadas seções paradérmicas e transversais, à mão livre e em micrótomo rotativo. Para cada espécie foram realizadas comparações das plantas infectadas com as sadias através de análises qualitativas e quantitativas. As alterações anatômicas observadas nas plantas infectadas foram a hiperplasia e hipertrofia de células parenquimáticas, depressões no limbo e desorganização do sistema vascular. P. setacea foi a espécie que, quando infectada com o vírus, apresentou menos alterações anatômicas, sendo selecionada para o estudo de diversidade genética. Para tanto, foram coletadas folhas jovens de 18 populações no estado da Bahia, nas regiões do Centro-Sul e Chapada Diamantina, totalizando 147 indivíduos, e testados 55 loci de SSR, dos quais seis foram selecionados para as análises. Os resultados das análises bayesiana de estruturação genética e da análise fenética indicaram a existência de dois grupos genéticos no estado, que não apresentaram correlação significativa com as distâncias geográficas. A AMOVA mostrou grande diversidade interpopulacional (45%), apesar do maior percentual de variação intrapopulacional (55%). Foi encontrado um Gst médio de 0,221 indicando um alto nível de estruturação genética entre as populações. As populações de maior diversidade foram as de Licínio de Almeida e Caetité, com maior percentual de polimorfismo, além de pertencerem a grupos genéticos distintos, sendo, portanto, consideradas as mais promissoras para enriquecimento de bancos de germoplasma de P. setacea e utilização em programas de melhoramento genético do maracujá. / The passion fruit, Passiflora sp., has great economic importance in Brazil, the country the world's leading producer of fruit and important gender diversity center. Pests are the main problems affecting the culture, and among them stands out the passion fruit woodiness disease, caused mainly by the Cowpea aphid-borne mosaic virus, CABMV. An effective control measure for this disease has not yet known, so that they are indispensable alternative techniques for its control and management. In this context, the genetic improvement of passion fruit can be held from wild species that are resistant to diseases and pests. This work aimed: a) to evaluate the anatomical changes resulting from infection with CABMV in five species of Passiflora (P. edulis f. flavicarpa, P cincinnata, P. gibertii, P. maliformis and P. setacea) and b) to evaluate the genetic diversity in populations of species with smaller anatomical changes resulting from infection. For anatomical assessment was established a bioassay, consisting of six plants of each species, of which half were mechanically inoculated with an isolated characterized the CABMV and the other half only inoculated with inoculation buffer. After 60 days of inoculation, they were collected as samples, the fifth leaf from the apex to the base of each plant. Samples were fixed in FAA and later preserved in 70% ethanol, were subsequently held paradermic and cross sections, freehand and rotary microtome. For each species comparisons were made of plants infected with sound through qualitative and quantitative analysis. The anatomical changes observed in infected plants were hyperplasia and hypertrophy of parenchyma cells, depressions in limbo and disorganization of the vascular system. P. setacea was the kind that when infected with the virus, had fewer anatomical changes, being selected for the study of genetic diversity. To this end, young leaves of 18 populations were collected in the state of Bahia, in the regions of South-Central and Chapada Diamantina, totaling 147 individuals, and 55 tested loci SSR, of which six were selected for analysis. The results of bayesian analysis of genetic structure and phenetics analysis indicated the existence of two genetic groups in the state, which showed no significant correlation with the geographical distances. The AMOVA showed great inter-population diversity (45%), despite the higher percentage of intra-population variation (55%). An average Gst was found of 0.221 indicating a high level of genetic structure among populations. The populations of most diversity were Licinio de Almeida and Caetité, with the highest percentage of polymorphism, in addition to belonging to different genetic groups and they are therefore considered the most promising for enrichment of P. setacea genebanks and use in breeding programs of passion fruit.

High anxiety is associated with an increased risk of developing cardiovascular disease (CVD), in particular, atherosclerotic coronary artery disease. However, the mechanisms by which anxiety contributes to the development of CVD are unclear. Unlike other common psychiatric disorders such as depression, anxiety and its effects on CVD risk has not been studied extensively. Moreover, whether elevated anxiety is associated with arterial stiffness and vascular endothelial dysfunction, biomarkers of CVD risk, in healthy adults and whether a psychological intervention designed to lower anxiety levels in healthy adults with moderate to high baseline anxiety levels ameliorates vascular dysfunction remains unclear. The purpose of this study was twofold; first to determine the extent to which moderate to high anxiety levels are associated with vascular dysfunction including aortic stiffness as measured by carotid-femoral pulse wave velocity (cf-PWV), carotid artery stiffness via ultrasound-based β-stiffness index, and forearm resistance artery function measured as peak forearm blood flow using venous occlusion plethysmograph (VOP). Secondly, to determine whether the empirically validated Acceptance and Commitment Training (ACT) anxiety intervention improved vascular function after 12 weeks and if this was associated with reductions in anxiety in adults with moderate to high baseline anxiety levels. Our results indicated that there was no association between increased anxiety levels and any of the three vascular outcomes of interest. Conversely, there was an association between the ACT intervention participation and improvement in forearm resistance artery function independent of age, sex, education, race/ethnicity, BMI and STAI Trait anxiety. Taken together, these data suggest that although higher State and Trait anxiety was not associated with aortic stiffness, carotid stiffness or forearm resistance artery function, and the ACT intervention was associated with improved peripheral resistance artery function. Additional studies are needed to determine whether this effect occurs earlier than 12 weeks and sustained longer that 12 weeks, and whether it occurs in adults with CVD risk factors (i.e. atherosclerosis), non-white racial/ethnic backgrounds and in resistance vessel function in response to intra-arterial vasoactive agonists such as acetylcholine.

Radio signals from Global Navigation Satellite Systems (GNSS) satellites suffer delay as they propagate through the atmosphere (neutral and non-neutral) and this delay is partially driven by the water vapour content in the atmosphere. The delay component due to the non-neutral atmosphere (ionosphere) is removed through the use of dual frequency GNSS receivers. The main tropospheric parameter is the zenith tropospheric (or total) delay (ZTD), which is a widely accepted parameter with which to express the total delay in the signal from all satellites due to the neutral atmosphere. The ZTD is a measure of the integrated tropospheric condition over a GNSS receiver station. Accordingly, the integrated water vapour or precipitable water vapour (PWV) can be obtained from a portion of the ZTD, if the atmospheric pressure and temperature at the station are known through a concept often referred to as GNSS meteorology. A number of GNSS receivers have been deployed for mapping and geodetic services in Nigeria under the African reference frame initiative, but unfortunately most of these receivers do not have co-located meteorological sensors for pressure and temperature measurements. The prospect of incorporating GNSS meteorology into weather monitoring and climate analysis in Nigeria was investigated and is reported in this thesis. During the first task of this research, the technical basis for ground-based GNSS meteorology was reviewed and the potentials and challenges of the approach to meteorological activities in Africa (including Nigeria) were identified. Thereafter an in-depth analysis of the spatial and temporal variability of ZTD over Nigeria for the period of 2010-2014 was conducted; results revealed weak spatial dependence among the stations. Tidal oscillations (of the diurnal and semidiurnal components) were observed at the GNSS stations of which the diurnal ZTD cycles exhibited significant seasonal dependence, affirming the prospective relevance of ground-based GNSS data to atmospheric studies. Also in this research, the accuracy and suitability of using reanalysis datasets (ERA-Interim and NCEP/NCAR) and a GPT2 neutral model in retrieving PWV from GNSS observations over Nigeria were investigated; results showed that PWV can be retrieved to within a precision of about 1 mm, provided GNSS-derived ZTD is of high precision. A fundamental issue for GNSS meteorology in the West African region was yet again addressed in this research; this is the development of a weighted tropospheric mean temperature model for use in current and future GNSS meteorology activities in the region. A multitechnique comparison of PWV estimates showed good agreement between GNSS estimates and other techniques (i.e. the atmospheric infrared sounder, and ERAInterim reanalysis). This result is suggestive of the potential of assimilating GNSS atmospheric products into reanalysis and climate models. Diurnal and seasonal variability of GNSS PWV estimates exhibits strong correlation with weather events that influence the region (i.e. solar activity and rainfall events); this further demonstrated the immense contribution of the approach to efficient weather forecasting and climate monitoring for Nigeria. / Thesis (PhD)--University of Pretoria, 2017. / Geography, Geoinformatics and Meteorology / PhD / Unrestricted

<p>Arterial stiffness is a natural and inevitable process for an ageing artery. In adults and school-aged children, increased stiffness of the central arteries is associated with cardiovascular disease (CVD) and CVD risk factors. Arterial stiffness, and its relationship with adiposity and physical activity (PA), has not been studied in preschool-aged children (3-5 years) despite the high prevalence of obesity and inactivity in this age group. Ninety-eight healthy preschoolers (4.4 ± 0.9 years; 50% boys) participated in this thesis, completing baseline and follow up assessments 12.5 ± 1.1 months apart. Whole-body PWV (carotid to dorsalis pedis; m/s) was used to assess arterial stiffness, body mass index percentile (BMI%ile) was a surrogate measure of adiposity, and PA levels (total, TPA; moderate-to-vigorous, MVPA) were quantified objectively with accelerometers and expressed as a percent of wear time. In our cohort, PWV increased significantly from baseline (4.3 m/s) to follow up (4.8 m/s; p< .001). PWV also tracked fair-to-moderately well (κ=0.25, r=0.37) with no sex differences (χ²=.485, p=.785). Girls had a higher BMI%ile than boys, and the prevalence of overweight/obese preschoolers increased from 18.8% to 21.3% over the 1-year period. Boys were more active than girls and engaged in more MVPA. 75% of preschoolers at baseline, and 70% at follow up, met the current PA guidelines (3-hrs of TPA/day). PWV was not related to BMI%ile or PA at baseline; however, it was weakly related to TPA (r=-0.28, p=.013) and MVPA (r=-0.25, p=.024) at follow up. Furthermore, longitudinal and cross-sectional regression models of sex, age, BMI%ile and TPA or MVPA could not predict PWV. Our findings indicate that adiposity and PA do not influence arterial stiffness in healthy 3 to 5 year old children. Nevertheless, maintaining a healthy body composition and engaging in regular PA has other health benefits and should be encouraged.</p> / Master of Science (MSc)