Peak oxygen uptake (VO2PEAK) in endurance exercise trained (ET =8) subjects (VO2PEAK = 61.7 1.6 ml 02.kg.min-1) was compared to the V02 PEAK of untrained (UT = 8) subjects (V02 PEAK = 38.4 1.7 ml 02 -kg.min1) after four hours of -6* head-down rest (HDR).Although both groups showed a reduction in blood volume (BV) following HDR, this decrement was greater for ET subjects (delta BV = -3.23 0.46 mi/kg; P <0.05). The ET subjects had a greater decrease in VO2=(delta 02E -5.58 1.05 ml 02-kg.min-1; P <0.05) than their UT peers (VO2PEAK = -2.44 0.79 ml02-kg.min-1). These data suggest that the greater reductions in VO2PE, observed for the ET group were associated with a greater BV loss resulting from 4 h of HDR prior to exercise.

Magister Public Health - MPH / The aim of the study was to explore the challenges to uptake of cervical cancer screening among women accessing maternal and child health services at Nsambya Hospital in Kampala, Uganda.

Master of Science / Department of Agronomy / Ignacio Ciampitti / Soybean [Glycine max (L.) Merr.] yields have continuously increased over time. Seed yields are determined by the genotype, environment, and management practices (G × E × M) interaction. Closing yield gaps require a continuous improvement in the use of the available resources, which must be attained via implementation of better management decisions. Linear relationships between seed yield and nitrogen (N) demand are reported in the scientific literature. Main sources of N to the plant are the biological N fixation (BNF) and the soil mineralization processes. On overall, only 50-60% of soybean N demand is met by the BNF process. An unanswered scientific knowledge is still related to the ability of the BNF to satisfy soybean N demand at varying yield levels. Seed N demand not met by N fixation plus soil mineral N, is then fulfilled by the remobilization of N from vegetative organs during the seed filling period. An early remobilization process reduces the photosynthetic activity (leaves) and can limit seed yield. The objectives of this project were to: i) study yield improvements and contribution of N via utilization of contrasting N conditions under historical and modern soybean genotypes, and ii) quantify main seed N sources during the seed filling period. For objective one, four field experiments were conducted during the 2016 and 2017 growing seasons in Kansas, United States (US) and Santa Fe Province, Argentina (ARG). Those experiments investigated twenty-one historical and modern soybean genotypes with release decades from 1980s to 2010s. As for objective two, three field experiments were conducted during the 2015 and 2016 growing seasons in Kansas, US, studying three soybean genotypes: non-roundup ready (RR), released in 1997; RR-1, released in 2009; and RR-2, released in 2014. Across all studies, seeds were inoculated and tested under three N management strategies: i) control without N application (Zero-N); ii) 56 kg N ha-1 applied at reproductive growth stages (Late-N); and iii) 670 kg ha-1 equally split at three timings (Full-N). As for yield improvements and N limitation, soybean yield improvements from the 1980s to 2010s were documented, representing 29% increases in the US and 21% in ARG. Regarding N management, the Full-N fertilization produced a 12% increase in seed yields in the US and 4% in ARG. As for main seed N sources in objective two, remobilization accounted for 59% of seed N demand, and was negatively related to new N uptake occurring during the seed filling period. Seed N demand for greater yields was dependent on both, N remobilization and new N uptake, while for lower yields, seed N demand was mainly supported by the N remobilization process. These results suggest that: a) high seed yields are somehow limited by the availability of N to express their potential, although the question about N application still remains to be fully investigated, as related to the timing and the environment by plant interactions that could promote a N limitation in soybeans; b) remobilization accounts for majority (59%) of N sourced to the seed, and c) high yielding soybean (modern genotypes) rely on diverse N sources: the N remobilization process plus new uptake of N.

Depuis leur découverte en 1975 par Köhler et Milstein, le monde des Ac monoclonaux a beaucoup évolué. Ils occupent actuellement une place prépondérante dans la prise en charge de nombreux cancers. De nos jours, les Ac monoclonaux, ayant une AMM ou en essai clinique, sont tous de classe IgG voire IgG1. Cette classe d’Ac a cependant montré des limites à son utilisation, et l’étude d’autres isotypes d’Ac, comme les IgA, pourrait être intéressante. Les IgA, isotype d’Ac particulier en raison notamment de leur hétérogénéité dans les formes moléculaires, demeurent peu étudiées à l’instar des IgG. Dans ce travail, nous proposons un radiomarquage des IgA monomériques, polymériques et sécrétoires, avec le 99mTc par une méthode indirecte impliquant le 2-iminothiolane et le cœur tricarbonyl. Par le biais de ce radiomarquage, la biodistribution des IgA monomériques et polymériques après administration i.v. a été évaluée chez l’animal sain et chez l’animal porteur de tumeur à localisation muqueuse. Ces études nous ont permis d’entrevoir le potentiel diagnostique des IgA, mais aussi leur intérêt en thérapie ciblée de tumeurs à localisation muqueuse. D’autre part, grâce à leur résistance enzymatique et au phénomène de retranscytose, une nouvelle voie d’administration des Ac monoclonaux pourrait être développée. Dans cette optique, des IgA sécrétoires ont été administrées par voie orale lors d’études préliminaires de biodistribution. / Since their discovery in 1975, by Köhler and Milstein, monoclonal antibodies (mAbs) world has significantly evolved and they currently hold a prominent place in cancers care. Today, the mAbs, having a marketing authorization or in clinical trial, are all IgG class (IgG1). However, this Ab class showed limitations on its use, and the study of other isotypes, such as IgA, could be interesting. Unlike IgG, IgA, original isotype particularly because of their heterogeneity in molecular forms, remains understudied. In this work, we propose a radiolabeling of monomeric, polymeric and secretory IgA with 99mTc by an indirect method, involving 2-iminothiolane and tricarbonyl core. Biodistribution of radiolabeled monomeric and polymeric IgA was evaluated, after intravenous administration, in healthy animals and in mucosal tumor-bearing animals. These studies have allowed us to glimpse the IgA diagnostic potential, but also their interest in targeted therapy of tumors with mucosal localization. Moreover, thanks to their enzymatic strength and retranscytosis, a new administration route of mAbs could be developed. In this context, secretory IgA were administered orally in preliminary biodistribution studies.

Introduction: The participation profile of patients with chronic obstructive pulmonary disease (COPD) in pulmonary rehabilitation (PR) and the effectiveness of a video-based home exercise programme (VBHEP) were investigated using various research methods. Methods: The content analysis of the Move-On-Up exercise video against NICE guidelines and published research was performed. The video was evaluated for its suitability for use in VBHEP through focus groups involving UK population of patients with COPD and respiratory clinicians. Using the data from the content analysis and the focus groups, questionnaire items were synthesised for a national survey of both patients and clinicians. A study examined the relationship between participation in outpatient PR and patient measures of depression (Brief Assessment Depression Card), social support (Duke Social Support Index), multidimensional health locus of control (MHLC) and COPD severity (Medical Research Council dyspnea score). A randomised control trial (RCT) evaluated the effect of combining VBHEP and conventional outpatient PR on walking ability and PR benefit maintenance. The intervention arm received VBHEP concurrently with outpatient PR, while the control arm received only outpatient PR. Outcome measures included: the endurance shuttle walk test (ESWT), quality of life (QoL) (St George's Respiratory Questionnaire- SGRQ), MHLC and a modified Follick's activity diary. Measures were taken before PR, at the fourth and eighth weeks of PR and at six months post-PR. Focus groups were conducted between six and 20 months post-PR to evaluate patients' experience of and adherence to the use of VBHEP. Results: Critical review of 46 RCTs aided evaluation of the video demonstrating that the video content was consistent with both NICE recommendations and published research. The six focus groups that were part of the initial evaluation of the video involved 14 patients and 14 clinicians. The national survey generated responses from 60 patients and 62 clinicians; between 79 and 100% of respondents in each domain of the questionnaire indicated that the video is suitable for use. Fifty-one patients completed the study investigating the profile of patients participating in PR. The results indicated that depression has a moderate and negative statistically significant association with the uptake of PR (p < 0.05). Fifty-seven patients participated in the RCT [mean age 66.51 years (SD 9.96), mean FEV1% predicted 54.51% (SD 10.47)]. The results indicated that the use of VBHEP with outpatient PR has no significant additive effect in improving or maintaining the benefits of walking ability following PR (p<0.05). Seven patients participated in the follow-up focus groups where findings suggested that patients were still participating in VBHEP up to 20 months after it was first prescribed, though the frequency of its use appeared to diminish after PR ended. Conclusion: The Move-On-Up exercise video is suitable for VBHEP in patients with COPD. Patients with COPD and depression are less likely to take up a referral to PR compared to those without depression. The use of VBHEP concurrently with PR has no additive effect in improving or maintaining benefits of walking ability following PR. Adverse social circumstances and disease severity reduce the duration of participation in VBHEP.

No description available.

Avec une prévalence de 1% dans la population générale, le trouble bipolaire (TB) est une maladie psychiatrique commune, chronique et sévère. Les études familiales réalisées pour cette affection ont montré une contribution génétique forte dans la prédisposition au TB, plus particulièrement pour les formes à début précoce de la maladie (TBDP). Malgré tout, les mécanismes moléculaires à l'origine de la maladie restent mal connus. Ainsi, suivant une étude de liaison génétique, nous avons pu identifier des variations rares dans un gène codant la protéine activatrice de l'exocytose dépendante du calcium (CADPS for Calcium- dependant activator protein for secretion) chez des patients avec un TBDP. CADPS est une protéine essentielle pour la régulation de l'exocytose et du chargement vésiculaire des monoamines dans les cellules neuronales et neuroendocrines. Nous avons étudié l'impact de ces mutations sur la fonction de ce gène, et montré que plusieurs d'entre elles altéraient son expression ainsi que ses fonctions. D'autre part, nous nous sommes intéressés au modèle murin privé d'un allèle de Caps (Caps1+/-) et montré que celles-ci décrivaient des comportements hyperactifs ainsi qu'une réponse au stress variable comparée aux souris sauvages.L'ensemble de nos résultats suggèrent pour la première fois que ce gène pourrait jouer un rôle dans les formes à début précoce de trouble bipolaire et ouvrent de nouvelles voies de recherche pour comprendre les mécanismes moléculaires qui sont altérés chez les sujets atteints. / Summary not transmitted

The use of nanomaterials (NMs) in orally ingestible products raises concerns about potential hazards. Titanium dioxide (TiO2) particles (of which some are incidentally produced at the nanoscale) are used in cosmetics, biological remediation (photo-catalysis), toothpastes, ingestible pharmaceuticals and food products. The increased surface area to mass ratio of nanoparticles (NPs) potentially makes them more biologically reactive than their coarser (bulk) material counterparts. There is limited data available on the uptake kinetics across the mammalian gastrointestinal tract, and the potential hazard posed to humans. In this study, the uptake and accumulation of TiO2 (nano and bulk) into and across the human intestinal cell line, the isolated perfused rat jejunum and the whole rat were evaluated. Caco-2 monolayers exhibited time-dependent, accumulation, uptake and transport of Ti/TiO2 from TiO2 exposures of 1 mg L-1 over 24 h, which was influenced by the crystal type, irrespective of cell maturity and growth substrate (Chapters 2-3). Electron micrographs of the Caco-2 monolayer showed the presence of particles inside the cells within vesicles and energy dispersive spectroscopy (EDS) confirmed the composition as TiO2. Addition of pharmacological inhibitors altered the Ti concentration in the cells suggesting diffusion is not the primary mechanism of uptake, rather, an active process is responsible (Chapter 2). Whole gut sacs exposures of 1 mg L-1 bulk or nano TiO2 demonstrated the primary regions of the gut associated with accumulation are the small and large intestine, with 70 % or more of the TiO2 accumulating in the mucosa rather than the underlying muscularis. Perfused intestines exposed to 1 mg L-1 bulk or nano TiO2 for 4 h showed a time-dependent accumulation of Ti in the serosal perfusate with the initial rates of Ti flux from the nano exposures being 5 fold higher than the bulk form. Addition of pharmacological inhibitors caused increases in tissue Ti concentration and significantly reduced Ti serosal flux rates for NP exposures. Overall, the data suggests an active absorption mechanism is responsible for Ti uptake from both bulk and nano TiO2 exposures across the perfused rat intestine that is drug sensitive (Chapter 4). In vivo work demonstrated feed status and rat age effected Ti tissue concentrations. Critically, Ti tissue concentrations reduced with increasing age and removal of Ti containing feed caused transient decreases in Ti tissue concentrations in 23 day old rats. Transient decreases in Ti tissue concentration following feed removal were not observed in older rats suggesting young rats may be more sensitive to the uptake hazards presented by titanium (Chapter 5). Overall, the findings presented in this thesis demonstrate Ti/TiO2 from both bulk and nano TiO2 exposures are accumulated and transported across intestinal epithelium and these processes are drug sensitive and affected by crystal structure and particle size. The results in this thesis have contributed to a better understanding of the uptake kinetics and sub-lethal hazards presented by bulk and nano forms of TiO2 exposed to intestinal epithelium which could be used to partially inform policy makers on human dietary risk assessments.

The increasing emergence and spread of antibiotic-resistant bacteria is a serious threat to public health. Of particular concern are Gram-negative bacteria such as Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae or Pseudomonas aeruginosa. Some of these strains are resistant to a large number of antibiotics and thus our treatment options are rapidly declining. In addition to the increasing number of antibiotic-resistant bacteria, a major problem is that many of the antibiotics at our disposal are ineffective against Gram-negative bacteria. This is partly due to the properties of the outer membrane (OM) which prevents efficient uptake. The overarching goal of this thesis was to investigate how the OM of the Gram-negative bacterium E. coli could be weakened to improve the activity of antibiotics. In the first two papers of my thesis (paper I + II), I investigated the periplasmic chaperone network which consists of the two parallel pathways SurA and Skp/DegP. This network is essential for the integrity of the OM and strains lacking either SurA or Skp are defective in the assembly of the OM, which results in an increased sensitivity towards vancomycin and other antimicrobials. We identified a novel component of the periplasmic chaperone network, namely YfgM, and showed that it operates in the same network as Skp and SurA/DegP. In particular, we demonstrated that deletion of YfgM in strains with either a ΔsurA or Δskp background further compromised the integrity of the OM, as evidenced by an increased sensitivity towards vancomycin. In the remaining two papers of my thesis (paper III + IV), the goal was to characterize small molecules that permeabilize the OM and thus could be used to improve the activity of antibiotics. Towards this goal, we performed a high-throughput screen and identified an inhibitor of the periplasmic chaperone LolA, namely MAC-13243, and showed that it can be used to permeabilize the OM of E. coli (paper III). We further demonstrated that MAC-13243 can be used to potentiate the activity of antibiotics which are normally ineffective against E. coli. In the last paper of my thesis (paper IV), we undertook a more specific approach and wanted to identify an inhibitor against the glycosyltransferase WaaG. This enzyme is involved in the synthesis of LPS and genetic inactivation of WaaG results in a defect in the OM, which leads to an increased sensitivity to various antibiotics. In this paper, we identified a small molecular fragment (compound L1) and showed that it can be used to inhibit the activity of WaaG in vitro. To summarize, this thesis provides novel insights into how the OM of the Gram-negative bacterium E. coli can be weakened by using small molecules. We believe that the two identified small molecules represent important first steps towards the design of more potent inhibitors that could be used in clinics to enhance the activity of antibiotics. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p>

Phytoplankton dynamics and chemical characteristics of the euphotic zone were measured from 1998-2000 (an El Niño/La Niña cycle) at the 5 major stations along Line P. Near-shelf and offshore stations exhibited low seasonality in chlorophyll and moderate seasonality in particulate organic carbon (POC) production. During the 1998 El Niño, June was characterized by low chlorophyll and POC productivity due to nitrate depletion. In contrast, during the 1999 La Niña, and in 2000, higher POC productivity and nitrate occurred in June. During 1999, chlorophyll and POC productivity were similar to 1998 in late summer. Near-shelf biomass was highest in June and lowest in Feb. for the near-shelf stations. High nitrate, low chlorophyll (HNLC) stations had the highest chlorophyll in Feb. followed by June. The coccolithophore assemblage was usually numerically dominated by Emiliania huxleyi, particularly in June. Along the transect, coccolithophore abundance was much higher in June during the 1998 El Niño than in the 1999 La Niña, with Aug./Sept. abundance of both years being very low. Higher abundances were measured along the transect in June and the late summer of 2000 with sporadic ‘blooms’ of >1000 cells ml⁻¹ at some stations. Particulate inorganic carbon (PIC) production was high along the transect during June 1998, and low during both winters, June 1999 and during late summers of 1998 and 1999. There was an increase in diatom biomass and >20 µm POC production during the 1998 El Niño, specifically in the farthest offshore HNLC stations, yet diatoms were rarely found to dominate total phytoplankton biomass or production. However, there were some sporadic examples of anomalously high diatom biomass (carbon and abundance) as well as >20 µm POC production, specifically at P12 in Aug./Sept 2000. The same major diatom species were found throughout Line P (near-shelf, P16, and HNLC). Integrated silica production measured by ³²Si ranged from 0.2 to 4.7 mmol Si m⁻² d⁻¹ between 1999-2000. Silicic acid and nitrate were never limiting at all stations in Feb. and generally increased in concentration along Line P during all seasons. / Science, Faculty of / Botany, Department of / Graduate