Body fat distribution in white and black women: different patterns of intraabdominal and subcutaneous abdominal adipose tissue utilization with weight loss.

BACKGROUND: Intraabdominal adipose tissue (IAAT) is the body fat depot most strongly related to disease risk. Weight reduction is advocated for overweight people to reduce total body fat and IAAT, although little is known about the effect of weight loss on abdominal fat distribution in different races. OBJECTIVE: We compared the effects of diet-induced weight loss on changes in abdominal fat distribution in white and black women. DESIGN: We studied 23 white and 23 black women, similar in age and body composition, in the overweight state [mean body mass index (BMI; in kg/m(2)): 28.8] and the normal-weight state (mean BMI: 24.0) and 38 never-overweight control women (mean BMI: 23.4). We measured total body fat by using a 4-compartment model, trunk fat by using dual-energy X-ray absorptiometry, and cross-sectional areas of IAAT (at the fourth and fifth lumbar vertebrae) and subcutaneous abdominal adipose tissue (SAAT) by using computed tomography. RESULTS: Weight loss was similar in white and black women (13.1 and 12.6 kg, respectively), as were losses of total fat, trunk fat, and waist circumference. However, white women lost more IAAT (P < 0.001) and less SAAT (P < 0.03) than did black women. Fat patterns regressed toward those of their respective control groups. Changes in waist circumference correlated with changes in IAAT in white women (r = 0.54, P < 0.05) but not in black women (r = 0.19, NS). CONCLUSIONS: Despite comparable decreases in total and trunk fat, white women lost more IAAT and less SAAT than did black women. Waist circumference was not a suitable surrogate marker for tracking changes in the visceral fat compartment in black women.

The Ciliogenic Transcription Factor RFX3 Regulates Early Midline Distribution of Guidepost Neurons Required for Corpus Callosum Development.

The corpus callosum (CC) is the major commissure that bridges the cerebral hemispheres. Agenesis of the CC is associated with human ciliopathies, but the origin of this default is unclear. Regulatory Factor X3 (RFX3) is a transcription factor involved in the control of ciliogenesis, and Rfx3-deficient mice show several hallmarks of ciliopathies including left-right asymmetry defects and hydrocephalus. Here we show that Rfx3-deficient mice suffer from CC agenesis associated with a marked disorganisation of guidepost neurons required for axon pathfinding across the midline. Using transplantation assays, we demonstrate that abnormalities of the mutant midline region are primarily responsible for the CC malformation. Conditional genetic inactivation shows that RFX3 is not required in guidepost cells for proper CC formation, but is required before E12.5 for proper patterning of the cortical septal boundary and hence accurate distribution of guidepost neurons at later stages. We observe focused but consistent ectopic expression of Fibroblast growth factor 8 (Fgf8) at the rostro commissural plate associated with a reduced ratio of GLIoma-associated oncogene family zinc finger 3 (GLI3) repressor to activator forms. We demonstrate on brain explant cultures that ectopic FGF8 reproduces the guidepost neuronal defects observed in Rfx3 mutants. This study unravels a crucial role of RFX3 during early brain development by indirectly regulating GLI3 activity, which leads to FGF8 upregulation and ultimately to disturbed distribution of guidepost neurons required for CC morphogenesis. Hence, the RFX3 mutant mouse model brings novel understandings of the mechanisms that underlie CC agenesis in ciliopathies.

Monoclonal antibodies identify a CEA crossreacting antigen of 95 kD (NCA-95) distinct in antigenicity and tissue distribution from the previously described NCA of 55 kD.

During the selection of monoclonal antibodies (MAb) raised against purified carcinoembryonic antigen (CEA), two MAbs were identified which immunoprecipitated a glycoprotein of 95 kD present both in perchloric acid extracts of normal lung and on the surface of normal granulocytes. This antigen was distinct from the previously reported normal glycoprotein crossreacting with CEA (NCA) which had a molecular weight of 55 kD. The difference between the smaller and the larger crossreacting antigens termed NCA-55 and NCA-95, respectively, was demonstrated by SDS-polyacrylamide gel electrophoresis, by elution from Sephadex-G200 and by selective binding to a series of anti-CEA MAb. Out of six MAb which all bound CEA purified from colon carcinoma, three did not react with these two crossreacting antigens, one bound only NCA-95, one reacted only with NCA-55 and one reacted with both NCA-55 and NCA-95. Immunoadsorbent purified preparations of 125I labelled NCA-95 and NCA-55 were found useful for the screening of new anti-CEA MAb. In addition, when tested on frozen sections of colon carcinoma, normal spleen, normal lung and pancreas, each type of MAb gave a clearly different pattern of reactivity. The three anti-CEA MAb which did not bind any of the crossreacting antigens stained only the colon carcinoma cells; the MAb binding to either one of the two types of NCA gave a similar pattern of reactivity both on colon carcinoma cells and on granulocytes. However, on normal lung and pancreas, the MAb binding NCA-55 stained granulocytes as well as bronchiolar and alveolar epithelial cells in lung and inter- and intra-lobular duct epithelial cells in pancreas, whereas the MAb binding only NCA-95 stained only the granulocytes. Thus, the newly identified NCA-95 appears to differ from NCA-55 not only in terms of molecular size and antigenicity but also by the fact that in normal lung and pancreas it is found in granulocytes but not in epithelial cells.

Multifractal portrayal of the distribution of the Swiss population

The present research studies the spatial patterns of the distribution of the Swiss population (DSP). This description is carried out using a wide variety of global spatial structural analysis tools such as topological, statistical and fractal measures, which enable the estimation of the spatial degree of clustering of a point pattern. A particular attention is given to the analysis of the multifractality to characterize the spatial structure of the DSP at different scales. This will be achieved by measuring the generalized q-dimensions and the singularity spectrum. This research is based on high quality data of the Swiss Population Census of the Year 2000 at a hectometric resolution (grid 100 x 100 m) issued by the Swiss Federal Statistical Office (FSO).

Distribution of arm velocity and frequency of arm usage during daily activity: objective outcome evaluation after shoulder surgery.

In clinical settings, functional evaluation of shoulder movement is primarily based on what the patient thinks he/she is able to do rather than what he/she is actually performing. We proposed a new approach for shoulder assessment based on inertial sensors to monitor arm movement in the daily routine. The detection of movement of the humerus relative to the trunk was first validated in a laboratory setting (sensitivity>95%, specificity>97%). Then, 41 control subjects and 21 patients suffering from a rotator cuff tear were evaluated (before and after surgery) using clinical questionnaires and a one-day measurement of arm movement. The quantity of movement was estimated with the movement frequency and its symmetry index (SIFr). The quality of movement was assessed using the Kolmogorov-Smirnov distance (KS) between the cumulative distribution of the arm velocity for controls and the same distribution for each patient. SIFr presented differences between patients and controls at 3 month follow-up (p<0.05) while KS showed differences also after 6 months (p<0.01). SIFr illustrated a change in dominance due to the disorder whereas KS, which appeared independent of the dominance and occupation, showed a change in movement velocity. Both parameters were correlated to clinical scores (R(2) reaching 0.5). This approach provides clinicians with new objective parameters for evaluating the functional ability of the shoulder in daily conditions, which could be useful for outcome assessment after surgery.

Ambulatory assessment of 3D ground reaction force using plantar pressure distribution.

This study aimed to use the plantar pressure insole for estimating the three-dimensional ground reaction force (GRF) as well as the frictional torque (T(F)) during walking. Eleven subjects, six healthy and five patients with ankle disease participated in the study while wearing pressure insoles during several walking trials on a force-plate. The plantar pressure distribution was analyzed and 10 principal components of 24 regional pressure values with the stance time percentage (STP) were considered for GRF and T(F) estimation. Both linear and non-linear approximators were used for estimating the GRF and T(F) based on two learning strategies using intra-subject and inter-subjects data. The RMS error and the correlation coefficient between the approximators and the actual patterns obtained from force-plate were calculated. Our results showed better performance for non-linear approximation especially when the STP was considered as input. The least errors were observed for vertical force (4%) and anterior-posterior force (7.3%), while the medial-lateral force (11.3%) and frictional torque (14.7%) had higher errors. The result obtained for the patients showed higher error; nevertheless, when the data of the same patient were used for learning, the results were improved and in general slight differences with healthy subjects were observed. In conclusion, this study showed that ambulatory pressure insole with data normalization, an optimal choice of inputs and a well-trained nonlinear mapping function can estimate efficiently the three-dimensional ground reaction force and frictional torque in consecutive gait cycle without requiring a force-plate.

Atmospheric deposition and migration of artificial radionuclides in Alpine soils (Val Piora, Switzerland) compared to the distribution of selected major and trace elements.

Artificial radionuclides ((137)Cs, (90)Sr, Pu, and (241)Am) are present in soils because of Nuclear Weapon Tests and accidents in nuclear facilities. Their distribution in soil depth varies according to soil characteristics, their own chemical properties, and their deposition history. For this project, we studied the atmospheric deposition of (137)Cs, (90)Sr, Pu, (241)Am, (210)Pb, and stable Pb. We compared the distribution of these elements in soil profiles from different soil types from an alpine Valley (Val Piora, Switzerland) with the distribution of selected major and trace elements in the same soils. Our goals were to explain the distribution of the radioisotopes as a function of soil parameters and to identify stable elements with analogous behaviors. We found that Pu and (241)Am are relatively immobile and accumulate in the topsoil. In all soils, (90)Sr is more mobile and shows some accumulations at depth into Fe-Al rich horizons. This behavior is also observed for Cu and Zn, indicating that these elements may be used as chemical analogues for the migration of (90)Sr into the soil.

Integrating species distribution models (SDMs) and phylogeography for two species of Alpine Primula.

The major intention of the present study was to investigate whether an approach combining the use of niche-based palaeodistribution modeling and phylo-geography would support or modify hypotheses about the Quaternary distributional history derived from phylogeographic methods alone. Our study system comprised two closely related species of Alpine Primula. We used species distribution models based on the extant distribution of the species and last glacial maximum (LGM) climate models to predict the distribution of the two species during the LGM. Phylogeographic data were generated using amplified fragment length polymorphisms (AFLPs). In Primula hirsuta, models of past distribution and phylogeographic data are partly congruent and support the hypothesis of widespread nunatak survival in the Central Alps. Species distribution models (SDMs) allowed us to differentiate between alpine regions that harbor potential nunatak areas and regions that have been colonized from other areas. SDMs revealed that diversity is a good indicator for nunataks, while rarity is a good indicator for peripheral relict populations that were not source for the recolonization of the inner Alps. In P. daonensis, palaeo-distribution models and phylogeographic data are incongruent. Besides the uncertainty inherent to this type of modeling approach (e.g., relatively coarse 1-km grain size), disagreement of models and data may partly be caused by shifts of ecological niche in both species. Nevertheless, we demonstrate that the combination of palaeo-distribution modeling with phylogeographical approaches provides a more differentiated picture of the distributional history of species and partly supports (P. hirsuta) and partly modifies (P. daonensis and P. hirsuta) hypotheses of Quaternary distributional history. Some of the refugial area indicated by palaeodistribution models could not have been identified with phylogeographic data.

Effects of alternative sets of climatic predictors on species distribution models and associated estimates of extinction risk: a test with plants in an arid environment

Aim To evaluate the effects of using distinct alternative sets of climatic predictor variables on the performance, spatial predictions and future projections of species distribution models (SDMs) for rare plants in an arid environment. . Location Atacama and Peruvian Deserts, South America (18º30'S - 31º30'S, 0 - 3 000 m) Methods We modelled the present and future potential distributions of 13 species of Heliotropium sect. Cochranea, a plant group with a centre of diversity in the Atacama Desert. We developed and applied a sequential procedure, starting from climate monthly variables, to derive six alternative sets of climatic predictor variables. We used them to fit models with eight modelling techniques within an ensemble forecasting framework, and derived climate change projections for each of them. We evaluated the effects of using these alternative sets of predictor variables on performance, spatial predictions and projections of SDMs using Generalised Linear Mixed Models (GLMM). Results The use of distinct sets of climatic predictor variables did not have a significant effect on overall metrics of model performance, but had significant effects on present and future spatial predictions. Main conclusion Using different sets of climatic predictors can yield the same model fits but different spatial predictions of current and future species distributions. This represents a new form of uncertainty in model-based estimates of extinction risk that may need to be better acknowledged and quantified in future SDM studies.

Distribution of metals exposure and associations with cardiometabolic risk factors in the "Modeling the Epidemiologic Transition Study".

BACKGROUND: Metals are known endocrine disruptors and have been linked to cardiometabolic diseases via multiple potential mechanisms, yet few human studies have both the exposure variability and biologically-relevant phenotype data available. We sought to examine the distribution of metals exposure and potential associations with cardiometabolic risk factors in the "Modeling the Epidemiologic Transition Study" (METS), a prospective cohort study designed to assess energy balance and change in body weight, diabetes and cardiovascular disease risk in five countries at different stages of social and economic development. METHODS: Young adults (25-45 years) of African descent were enrolled (N = 500 from each site) in: Ghana, South Africa, Seychelles, Jamaica and the U.S.A. We randomly selected 150 blood samples (N = 30 from each site) to determine concentrations of selected metals (arsenic, cadmium, lead, mercury) in a subset of participants at baseline and to examine associations with cardiometabolic risk factors. RESULTS: Median (interquartile range) metal concentrations (μg/L) were: arsenic 8.5 (7.7); cadmium 0.01 (0.8); lead 16.6 (16.1); and mercury 1.5 (5.0). There were significant differences in metals concentrations by: site location, paid employment status, education, marital status, smoking, alcohol use, and fish intake. After adjusting for these covariates plus age and sex, arsenic (OR 4.1, 95% C.I. 1.2, 14.6) and lead (OR 4.0, 95% C.I. 1.6, 9.6) above the median values were significantly associated with elevated fasting glucose. These associations increased when models were further adjusted for percent body fat: arsenic (OR 5.6, 95% C.I. 1.5, 21.2) and lead (OR 5.0, 95% C.I. 2.0, 12.7). Cadmium and mercury were also related with increased odds of elevated fasting glucose, but the associations were not statistically significant. Arsenic was significantly associated with increased odds of low HDL cholesterol both with (OR 8.0, 95% C.I. 1.8, 35.0) and without (OR 5.9, 95% C.I. 1.5, 23.1) adjustment for percent body fat. CONCLUSIONS: While not consistent for all cardiometabolic disease markers, these results are suggestive of potentially important associations between metals exposure and cardiometabolic risk. Future studies will examine these associations in the larger cohort over time.

Distribution profile of zwitterions and hydrolysis of esters derived from N-benzylpiperazine

Résumé Les esters sont des agents thérapeutiques largement utilisés comme médicaments et prodrogues. Leurs dégradation est chimique et enzymatique. Le Chapitre IV de cette thèse a comme objet l'hydrolyse chimique de plusieurs dérivés esters du 2,3-dimethoxyphenol. Des composés modèles ont été synthétisés dans le but de déterminer leur mécanismes de dégradation. Les profils d'ionisation et d'hydrolyse de ces composés ont permis d'identifier la présence d'une catalyse intramoléculaire basique par un atome d'azote non-protoné. Les effets électroniques exercés par les groupes phenylethenyle et phenylcyclopropyle influencent également la vitesse d'hydrolyse des esters. La résolution des problèmes liés à l'adsorption et la perméation est devenue à nos jours l'étape limitante dans la conception de nouveaux médicaments car de trop nombreux candidats prometteurs ont échoué à cause d'une mauvaise biodisponibilité. La lipophilie décrit le partage d'un médicament entre une membrane lipidique et son environnement physiologique aqueux, et de ce fait elle influence sa pharmacocinétique. Des études récents ont mis en évidence l'importance de la détermination de la lipophilie des espèces ionisées vu leur considérable impact biologique. Le Chapitre V de cette thèse est centré sur une classe particulière de composés ionisables, les zwitterions. Plusieurs methoxybenzylpiperazines de nature zwitterionique ont été étudiées. Leurs profils d'ionisation ont montré que dans un large intervalle de pH, l'espèce prédominante est le zwitterion. Les profils de lipophilie ont montré que leur lipophilie est plus élevée que celles des zwitterions courants. Une interaction électrostatique entre l'oxygène du carboxylate et l'azote protoné est responsable de ce profil et rend la plupart des zwitterions non-donneurs de liaison hydrogène. Ces deux aspects peuvent favoriser le passage de la barrière hémato-éncephalique. Les données biologiques ont par la suite confirmé cette hypothèse pour un certain nombre de composés. Résumé large public Les esters sont des composés souvent rencontrés en chimie thérapeutique. Ils sont dégradés en milieu aqueux par une réaction d'hydrolyse, avec ou sans la participation d'enzymes. Dans ce travail de thèse, une série d'esters ont été étudiés dans le but d'établir une relation entre leur structure et les mécanismes responsables de leur dégradation chimique. Il a été prouvé que la dégradation est accélérée par un atome d'azote non-protoné. D'autres mécanismes peuvent intervenir en fonction du pH du milieu. La présence d'une liaison simple ou double ou d'un groupe phenylcyclopropyle peut également influencer la vitesse de dégradation. Il est essentiel, dans la conception de nouveaux médicaments, d'optimiser les étapes qui influencent leur distribution dans le corps. Ce dernier peut être visualisé comme une série infinie de compartiments aqueux séparés par des membranes lipidiques. La lipophilie est une propriété moléculaire importante qui décrit le passage des barrières rencontrées par les médicaments. Des études récentes ont mis en évidence l'importance de déterminer la lipophilie des espèces ionisées vu leur considérable impact biologique. Dans ce travail de thèse a été étudiée une série particulière de composés ionisables , les zwitterions. Une relation a été établie entre leur structure et leur proprietés physico-chimiques. Une lipophilie plus élevée par rapport à celle des zwitterions courants a été trouvée. Une interaction entre les groupes chargés des zwitterions étudiés est responsable de ce comportement inattendu et rend la plupart d'entre eux non-donneurs de liaison hydrogène. Ces deux facteurs peuvent favoriser la pénétration cérébrale. Les données biologiques ont confirmé cette hypothèse pour un certain nombre de composés. Summary Esters are often encountered in medicinal chemistry. Their hydrolysis may be chemical as well as enzymatic. Chapter IV of this manuscript provides a mechanistic insight into the chemical hydrolysis of a particular series of basic esters derived from 2,3-dimethoxyphenol. Their ionization and pH-rate profiles allowed to identify the presence of an intramolecular base catalysis by a non-protonated nitrogen atom. Electronic effects exerted by the phenylethenyl and phenylcyclopropyl groups that are present in the structure of the esters also influenced their rate of hydrolysis. Numerous works in the literature witness of the importance of lipophilicity in determining the fate of a drug. Most published partition coefficients are those of neutral species. In contrast, no exhaustive treatment of the lipophilicity of charged molecules is available at present, and a lack of information characterizes in particular zwitterions. Chapter V of this manuscript provides an insight into the physicochemical parameters of a series of zwitterionic methoxybenzylpiperazines. Their ionization profiles showed that they exist predominantly in the zwitterionic form in a broad pH-range. An electrostatic interaction between the oxygen of the carboxylate and the protonated nitrogen atom is increases the lipophilicity of the investigated zwitterions, and prevents the majority of them to express their hydrogen-bonding capacity. These two aspects may favor the crossing of the blood-brain barrier. The available ratios PSt/PSf measured in vitro have confirmed this point for a number of compounds.

Are niche-based species distribution models transferable in space?

Aim To assess the geographical transferability of niche-based species distribution models fitted with two modelling techniques. Location Two distinct geographical study areas in Switzerland and Austria, in the subalpine and alpine belts. Methods Generalized linear and generalized additive models (GLM and GAM) with a binomial probability distribution and a logit link were fitted for 54 plant species, based on topoclimatic predictor variables. These models were then evaluated quantitatively and used for spatially explicit predictions within (internal evaluation and prediction) and between (external evaluation and prediction) the two regions. Comparisons of evaluations and spatial predictions between regions and models were conducted in order to test if species and methods meet the criteria of full transferability. By full transferability, we mean that: (1) the internal evaluation of models fitted in region A and B must be similar; (2) a model fitted in region A must at least retain a comparable external evaluation when projected into region B, and vice-versa; and (3) internal and external spatial predictions have to match within both regions. Results The measures of model fit are, on average, 24% higher for GAMs than for GLMs in both regions. However, the differences between internal and external evaluations (AUC coefficient) are also higher for GAMs than for GLMs (a difference of 30% for models fitted in Switzerland and 54% for models fitted in Austria). Transferability, as measured with the AUC evaluation, fails for 68% of the species in Switzerland and 55% in Austria for GLMs (respectively for 67% and 53% of the species for GAMs). For both GAMs and GLMs, the agreement between internal and external predictions is rather weak on average (Kulczynski's coefficient in the range 0.3-0.4), but varies widely among individual species. The dominant pattern is an asymmetrical transferability between the two study regions (a mean decrease of 20% for the AUC coefficient when the models are transferred from Switzerland and 13% when they are transferred from Austria). Main conclusions The large inter-specific variability observed among the 54 study species underlines the need to consider more than a few species to test properly the transferability of species distribution models. The pronounced asymmetry in transferability between the two study regions may be due to peculiarities of these regions, such as differences in the ranges of environmental predictors or the varied impact of land-use history, or to species-specific reasons like differential phenotypic plasticity, existence of ecotypes or varied dependence on biotic interactions that are not properly incorporated into niche-based models. The lower variation between internal and external evaluation of GLMs compared to GAMs further suggests that overfitting may reduce transferability. Overall, a limited geographical transferability calls for caution when projecting niche-based models for assessing the fate of species in future environments.