Eating patterns and prevalence of obesity. Lessons learned from the Malaysian Food Barometer.

The Malaysian society is experiencing and coping with a fast modernization process, which is characterized by a rapid urbanization and rural exodus, an important reduction of the size of households, and the emergence of a new middle class. The Malaysian Food Barometer launched in 2013 has provided better understanding how these macro issues have affected the lifestyles and especially the food habits of the Malaysians. The country has indeed undergone a transition period from under-nutrition to over-nutrition in a few decades, with the prevalence of overweight and obesity having markedly and rapidly increased. A quantitative survey (n = 2000), elaborated from a qualitative preliminary phase, was carried out with the aim of analyzing the transformation of food habits at the national level. The present article focuses on the BMI issue in Malaysia, and investigates its relationships with the socio-demographic variables of the population, as well as their eating patterns. The mean BMI is 23.64 kg/m2, with 9.5% of the sample being obese, and 22% overweight. Strong statistical associations have been identified between BMI and independent variables such as size of the living area, ethnicity, level of education, gender, and age. Contrary to general believe, overweight and obesity were neither associated with the number of food intakes taken per day (including snacks) nor with the frequency of eating out. Nonetheless, obesity is over-represented in people who have dissonant eating behaviors, i.e. who declare having fewer food intakes a day (food norms) than they do actually (food practices). This process testifies that the Malaysians are experiencing a "food transition", which is linked with socio-economic development.

Decreased STAT3 in human idiopathic fetal growth restriction contributes to trophoblast dysfunction.

Abnormal trophoblast function is associated with fetal growth restriction (FGR). The JAK-STAT pathway is one of the principal signalling mechanisms by which cytokines and growth factors modulate cell proliferation, differentiation, cell migration and apoptosis. The expression of placental JAK-STAT genes in human idiopathic FGR is unknown. In this study, we propose the hypothesis that JAK-STAT pathway genes are differentially expressed in idiopathic FGR-affected pregnancies and contribute to abnormal feto-placental growth by modulating the expression of the amino acid transporter SNAT2, differentiation marker CGB/human chorionic gonadotrophin beta-subunit (ß-hCG) and apoptosis markers caspases 3 and 8, and TP53. Expression profiling of FGR-affected placentae revealed that mRNA levels of STAT3, STAT2 and STAT5B decreased by 69, 52 and 50%, respectively, compared with gestational-age-matched controls. Further validation by real-time PCR and immunoblotting confirmed significantly lower STAT3 mRNA and STAT3 protein (total and phosphorylated) levels in FGR placentae. STAT3 protein was localised to the syncytiotrophoblast (ST) in both FGR and control placentae. ST differentiation was modelled by in vitro differentiation of primary villous trophoblast cells from first-trimester and term placentae, and by treating choriocarcinoma-derived BeWo cells with forskolin in cell culture. Differentiation in these models was associated with increased STAT3 mRNA and protein levels. In BeWo cells treated with siRNA targeting STAT3, the mRNA and protein levels of CGB/ß-hCG, caspases 3 and 8, and TP53 were significantly increased, while that of SNAT2 was significantly decreased compared with the negative control siRNA. In conclusion, we report that decreased STAT3 expression in placentae may contribute to abnormal trophoblast function in idiopathic FGR-affected pregnancies.

Reversibility of superconducting nb weak links driven by the proximity effect in a quantum interference device.

We demonstrate the role of the proximity effect in the thermal hysteresis of superconducting constrictions. From the analysis of successive thermal instabilities in the transport characteristics of micron-size superconducting quantum interference devices with a well-controlled geometry, we obtain a complete picture of the different thermal regimes. These determine whether or not the junctions are hysteretic. Below the superconductor critical temperature, the critical current switches from a classical weak-link behavior to one driven by the proximity effect. The associated small amplitude of the critical current makes it robust with respect to the heat generation by phase slips, leading to a nonhysteretic behavior.

Correlation of polarity and crystal structure with optoelectronic and transport properties of GaN/AlN/GaN nanowire sensors.

GaN nanowires (NWs) with an AlN insertion were studied by correlated optoelectronic and aberration-corrected scanning transmission electron microscopy (STEM) characterization on the same single NW. Using aberration-corrected annular bright field and high angle annular dark field STEM, we identify the NW growth axis to be the N-polar [000-1] direction. The electrical transport characteristics of the NWs are explained by the polarization-induced asymmetric potential profile and by the presence of an AlN/GaN shell around the GaN base of the wire. The AlN insertion blocks the electron flow through the GaN core, confining the current to the radial GaN outer shell, close to the NW sidewalls, which increases the sensitivity of the photocurrent to the environment and in particular to the presence of oxygen. The desorption of oxygen adatoms in vacuum leads to a reduction of the nonradiative surface trap density, increasing both dark current and photocurrent.

Comparative expression of hCG ß-genes in human trophoblast from early and late first-trimester placentas.

Human chorionic gonadotropin (hCG) displays a major role in pregnancy initiation and progression and is involved in trophoblast differentiation and fusion. However, the site and the type of dimeric hCG production during the first trimester of pregnancy is poorly known. At that time, trophoblastic plugs present in the uterine arteries disappear, allowing unrestricted flow of maternal blood to the intervillous space. The consequence is an important modification of the trophoblast environment, including a rise of oxygen levels from about 2.5% before 10 wk of amenorrhea (WA) to ∼8% after 12 WA. Two specific ß-hCG proteins that differ from three amino acids have been described: type 1 (CGB7) and type 2 (CGB3, -5, and -8). Here, we demonstrated in situ and ex vivo on placental villi and in vitro in primary cultures of human cytotrophoblasts that type 1 and 2 ß-hCG RNAs and proteins were expressed by trophoblasts and that these expressions were higher before blood enters in the intervillous space (8-9 vs. 12-14 WA). hCG was immunodetected in villous mononucleated cytotrophoblasts (VCT) and syncytiotrophoblast (ST) at 8-9 WA but only in ST at 12-14 WA. Furthermore, hCG secretion was fourfold higher in VCT cultures from 8-9 WA compared with 12-14 WA. Interestingly, VCT from 8-9 WA placentas were found to exhibit more fusion features. Taken together, we showed that type 1 and type 2 ß-hCG are highly expressed by VCT in the early first trimester, contributing to the high levels of hCG found in maternal serum at this term.

The THEMA study: a sociodemographic survey of hypercholesterolaemic individuals.

BACKGROUND: Hypercholesterolaemia is estimated to affect 20% of the population, although little sociodemographic information is available on affected individuals. The present study aimed to gather relevant information and investigate social determinants of dietary compliance. METHODS: A telephone survey was carried out on a representative population sample. Quotas were applied for gender, geography and degree of urbanisation. Individuals were eligible if they were hypercholesterolaemic, and were being followed by a doctor. Sociodemographic, socioeconomic and health data were collected, as well as information about the individuals' perception of the disease, their relationship and beliefs surrounding food, and their food behaviour (shopping, cooking, eating-out, deviation from prescribed diet). The association between compliance with diet and medication was investigated. RESULTS: Overall, 802 individuals were included, representing 8% of those contacted, as opposed to the expected 20%. Mean (SD) age was 60 (14.2) years, with 51% of individuals living as a couple; 48% had a good level of physical activity; 44% considered that the hypercholesterolaemia was inherited; 31% felt that the disease was normal beyond the age of 45 years. The functional and convivial aspects of eating were of more importance than that of health maintenance. Cheese was particularly likely to be eaten in dietary lapses. Of a subgroup of 729 individuals, 476 (65%) took medication; of these 476 individuals, 51% complied with dietary recommendations (P < 0.05). CONCLUSIONS: The key factors associated with dietary compliance in hypercholesterolaemic individuals were identified: age, sex, the perceptions of hypercholesterolaemia, and the sociocultural aspects of food. By contrast to general assumptions, both dietary and medicinal measures are practised fairly well by a large proportion of these individuals.

Mesoscopic size effects on the thermal conductance of silicon nanowire.

We report the measurement of thermal conductance of silicon nanowires at low temperature. It is demonstrated that the roughness at the nanometer scale plays a crucial role for the phonon transport in low-dimensional samples. To this end, using e-beam lithography, nanowires of size 200 nm by 100 nm and 10 microm long have been nanofabricated. Their thermal properties have been measured using the 3 omega method between 0.3 and 6 K. The change in the temperature behavior of the thermal conductance (quadratic temperature dependence of K(T)) is a signature of an intermediate regime lying between the classical Casimir regime and the quantum regime. The Casimir-Ziman model is used to show that this specific behavior originates in mesoscopic samples where the dominant phonon wavelength becomes commensurate to the characteristic length of the roughness of the nanowire surfaces.

Placental production of progestins is fully effective in villous cytotrophoblasts and increases with the syncytiotrophoblast formation.

Placental syncytiotrophoblast (ST) is considered as the main placental endocrine tissue secreting progesterone, a steroid essential for maintenance of pregnancy. However, each step of progestins production has been poorly investigated in villous cytotrophoblast (VCT) regarding ST formation. We aimed to characterize progestins production during human differentiation of VCT into ST. VCTs were isolated from term placenta and cultivated, with or without forskolin (FSK), to stimulate trophoblast differentiation. Secreted progestins concentrations were determined by immuno-assay and Gas Chromatography-tandem mass spectrometry. Intracellular expression of cholesterol transporter and enzymes involved in steroidogenesis were studied by immunofluorescence, western-blot, and RT-qPCR. Progesterone and pregnenolone are produced by VCT and their secretion increases with VCT differentiation while 17-hydroxyprogesterone concentration remains undetectable. HSD3B1 enzyme expression increases whereas MLN64, the cholesterol placental mitochondrial transporter and P450SCC expressions do not. FSK induces progestins production. Progestins placental synthesis is effective since VCT and increases with ST formation thanks to mitochondria.

Contacting individual Fe(110) dots in a single electron-beam lithography step.

We report on a new approach, entirely based on an electron-beam lithography technique, to contact electrically, in a four-probe scheme, single nanostructures obtained by self-assembly. In our procedure, nanostructures of interest are located and contacted in the same fabrication step. This technique has been developed to study the field-induced reversal of an internal component of an asymmetric Bloch domain wall observed in elongated structures such as Fe(110) dots. We have focused on the control, using an external magnetic field, of the magnetization orientation within Néel caps that terminate the domain wall at both interfaces. Preliminary magneto-transport measurements are discussed demonstrating that single Fe(110) dots have been contacted.

[Current debates on immunology of preeclampsia. Report of the sixth international workshop of Reunion Island (Indian Ocean, December 2008)]. / Débats actuels sur l'immunologie de la prééclampsie. Comptes rendus du sixième colloque international de La Réunion (décembre 2008).

Hypertensive disorders of pregnancy (HDP) represent globally 10% of human births and their major complication, preeclampsia, 3 to 5%. The etiology of these HDP remains still uncertain, however major advances have been made these last 25 years. The Sixth International Workshop on Reproductive Immunology, Immunological Tolerance and Immunology of Preeclampsia 2008 celebrated its 10th Anniversary in Reunion-island (French overseas Department in the Indian Ocean). Over this decade, these six workshops have contributed extensively to immunological, epidemiological, anthropological and even vascular debates. The defect of trophoblastic invasion encountered in preeclampsia, intra-uterine growth retardation and to some extend also preterm labour has been understood only at the end of the 1970's. On the other hand, clinical and epidemiological findings at the end of the 20th century permitted to apprehend that "preeclampsia disease of primiparae" may in fact well be the disease of first pregnancies at the level of human couples. Among the important advances, immunology of reproduction is certainly the topic where knowledge has literally exploded in the last decade. This paper relates some major steps in comprehension of this disease and focuses on the interest to follow these immunological works and their new concepts. It seems, at the beginning of the 21st century, that we are possibly closer than ever to understand the etiology of this obstetrical enigma. In this quest, the immunology of reproduction will certainly come out as one of the main players.

Steady-state expression of self-regulated genes.

MOTIVATION: Regulatory gene networks contain generic modules such as feedback loops that are essential for the regulation of many biological functions. The study of the stochastic mechanisms of gene regulation is instrumental for the understanding of how cells maintain their expression at levels commensurate with their biological role, as well as to engineer gene expression switches of appropriate behavior. The lack of precise knowledge on the steady-state distribution of gene expression requires the use of Gillespie algorithms and Monte-Carlo approximations. METHODOLOGY: In this study, we provide new exact formulas and efficient numerical algorithms for computing/modeling the steady-state of a class of self-regulated genes, and we use it to model/compute the stochastic expression of a gene of interest in an engineered network introduced in mammalian cells. The behavior of the genetic network is then analyzed experimentally in living cells. RESULTS: Stochastic models often reveal counter-intuitive experimental behaviors, and we find that this genetic architecture displays a unimodal behavior in mammalian cells, which was unexpected given its known bimodal response in unicellular organisms. We provide a molecular rationale for this behavior, and we implement it in the mathematical picture to explain the experimental results obtained from this network.

Avian influenza in Vietnam: chicken-hearted consumers?

This study, based on quantitative and qualitative surveys conducted from July 2004 to September 2005, examines the perceptions of Hanoi consumers and their reactions to the Avian Influenza epizootic (H5N1). Hanoi consumers clearly link the risk of human contamination by the virus to the preparation and ingestion of poultry. During the first crisis, consumers reacted quickly and intensely (74% of them had already stopped eating poultry in January 2004). Nevertheless, once the crisis abated, they quickly resumed their consumption of poultry. This behavior corresponds to the pattern described by empirical studies of other crises, such as BSE. What is more surprising is the speed with which the different steps of this common pattern succeeded one another. It may be explained by a rapid decrease in risk anxiety. A logit model shows that, soon after the beginning of the crisis, AI risk anxiety was tempered by confidence in the information and recommendations issued by the government concerning AI and, in the long term, by a high perceived self-efficiency to deal with AI. Indeed, not only has poultry consumption been affected in terms of the quantity consumed, but alternative ways of selecting and preparing poultry have also been adopted as anti-risk practices. Risk communication strategies should take this into account, and rely on a previous assessment of consumer practices adopted to deal with the risk.

[Pathophysiology of preeclampsia]. / Physiopathologie de la prééclampsie.

Preeclampsia is a human disease, usually occurring during the third trimester of pregnancy. The underlying pathogenetic mechanisms of preeclampsia are much debated. Current hypotheses include placental dysfunction, inflammatory disease, genetic predisposition and immune maladaptation. Recent studies highlight the role of vascular-mediated factors in the pathophysiology of preeclampsia and allow new hopes for screening and therapeutic approaches. This article describes pathophysiological mechanisms involved in the defective uteroplacental vascularization leading to placental and endothelial dysfunction.

Induction of diaphragmatic nitric oxide synthase after endotoxin administration in rats: role on diaphragmatic contractile dysfunction.

Nitric oxide (NO), a free radical that is negatively inotropic in the heart and skeletal muscle, is produced in large amounts during sepsis by an NO synthase inducible (iNOS) by LPS and/or cytokines. The aim of this study was to examine iNOS induction in the rat diaphragm after Escherichia Coli LPS inoculation (1.6 mg/kg i.p.), and its involvement in diaphragmatic contractile dysfunction. Inducible NOS protein and activity could be detected in the diaphragm as early as 6 h after LPS inoculation. 6 and 12 h after LPS, iNOS was expressed in inflammatory cells infiltrating the perivascular spaces of the diaphragm, whereas 12 and 24 h after LPS it was expressed in skeletal muscle fibers. Inducible NOS was also expressed in the left ventricular myocardium, whereas no expression was observed in the abdominal, intercostal, and peripheral skeletal muscles. Diaphragmatic force was significantly decreased 12 and 24 h after LPS. This decrease was prevented by inhibition of iNOS induction by dexamethasone or by inhibition of iNOS activity by N(G)-methyl-L-arginine. We conclude that iNOS was induced in the diaphragm after E. Coli LPS inoculation in rats, being involved in the decreased muscular force.

Involvement of PPARgamma in human trophoblast invasion.

The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the nuclear receptor superfamily that controls the expression of a large array of genes in a ligand-dependent manner. In the human placenta, PPARgamma is specifically expressed in the villous cytotrophoblast and syncytiotrophoblast as well as in the extravillous cytotrophoblastic cells (EVCT) along their invasive pathway. The present study used two cellular models, primary cultures of trophoblastic cells differentiated in vitro in extravillous trophoblastic cells and a cell line (HIPEC65), which was established from a primary culture of EVCT transformed by T-SV40. We observed that natural (15d-PGJ2) or synthetic ligands of PPARgamma (rosiglitazone) inhibit cell invasion in a concentration-dependent manner, with no effect on cell proliferation. This is associated with a modulation of the expression of trophoblastic genes described to be directly involved in the control of EVCT invasiveness, such as GH-V (-20%), TGFbeta2 (-30%), PAPP-A (-60%) and IL1beta (+300%.). In order to identify PPARgamma potential ligands at the fetomaternal interface, we purified LDL (low density lipoprotein) from human sera and oxidized them in vitro in the presence of copper. OxLDL inhibit in vitro extravillous trophoblast cell invasion, whereas native LDL have no effect. In situ OxLDL and their LOX-1 receptor, as well as PPARgamma are immunodetected in trophoblasts at the maternofetal interface.

PPARs and the placenta.

The discovery of the peroxisome proliferator-activated receptors (PPARs) in 1990s provided new insights in understanding the mechanisms involved in the control of energy homeostasis and in cell differentiation, proliferation, apoptosis and the inflammatory process. The PPARs became thus an exciting therapeutic target for diabetes, metabolic syndrome, atherosclerosis, and cancer. Unexpectedly, genetic studies performed in mice established that PPARgamma are essential for placental development. After a brief description of structural and functional features of PPARs, we will summarize in this review the most recent results concerning expression and the role of PPARs in placenta and of PPARgamma in human trophoblastic cells in particular.

Human chorionic gonadotropin expression in human trophoblasts from early placenta: comparative study between villous and extravillous trophoblastic cells.

Human trophoblast differentiates into two pathways: extravillous cytotrophoblasts (EVCT) that invade the uterus wall and villous cytotrophoblasts (VCT) that fuse to form the syncytiotrophoblast (ST) involved in placental exchanges and endocrine function. It is established that hCG is produced and secreted by the ST into the maternal compartment where it plays a key endocrine role and stimulates ST formation in an autocrine manner. Herein, we investigated hCG expression in early placentas by immunohistochemistry using different antibodies. We then compared hCG secretion by primary cultures of VCT and EVCT isolated from the same first trimester human chorionic villi. In situ hCG was immunodetected in EVCT all along their invasive differentiating pathway except in cells near the stromal core of the proximal column. hCG expression was confirmed in vitro by immunocytochemistry and hCG secretion quantified in cell supernatants. Interestingly, whereas hCG secretion increased during VCT differentiation into ST (from 60 to 350UI/L/microg DNA), EVCT secretion remained constant and at a high level during the same culture period (160UI/L/microg DNA). Our data demonstrated that in addition to the ST, invasive EVCT also expressed and secreted high levels of hCG, suggesting a specific paracrine and/or autocrine role for hCG from EVCT origin.

Electron and phonon cooling in a superconductor-normal-metal-superconductor tunnel junction.

We present evidence for the cooling of normal-metal phonons, in addition to the well-known electron cooling, by electron tunneling in a superconductor-normal-metal-superconductor tunnel junction. The normal-metal electron temperature is extracted by comparing the device current-voltage characteristics to the theoretical prediction. We use a quantitative model for the heat transfer that includes the electron-phonon coupling in the normal metal and the Kapitza resistance between the substrate and the metal. It gives a very good fit to the data and enables us to extract an effective phonon temperature in the normal metal.

The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase.

Stimulation of the hepatocyte growth factor (HGF) receptor tyrosine kinase, Met, induces mitogenesis, motility, invasion, and branching tubulogenesis of epithelial and endothelial cell lines in culture. We have previously shown that Gab1 is the major phosphorylated protein following stimulation of the Met receptor in epithelial cells that undergo a morphogenic program in response to HGF. Gab1 is a member of the family of IRS-1-like multisubstrate docking proteins and, like IRS-1, contains an amino-terminal pleckstrin homology domain, in addition to multiple tyrosine residues that are potential binding sites for proteins that contain SH2 or PTB domains. Following stimulation of epithelial cells with HGF, Gab1 associates with phosphatidylinositol 3-kinase and the tyrosine phosphatase SHP2. Met receptor mutants that are impaired in their association with Gab1 fail to induce branching tubulogenesis. Overexpression of Gab1 rescues the Met-dependent tubulogenic response in these cell lines. The ability of Gab1 to promote tubulogenesis is dependent on its pleckstrin homology domain. Whereas the wild-type Gab1 protein is localized to areas of cell-cell contact, a Gab1 protein lacking the pleckstrin homology domain is localized predominantly in the cytoplasm. Localization of Gab1 to areas of cell-cell contact is inhibited by LY294002, demonstrating that phosphatidylinositol 3-kinase activity is required. These data show that Gab1 is an important mediator of branching tubulogenesis downstream from the Met receptor and identify phosphatidylinositol 3-kinase and the Gab1 pleckstrin homology domain as crucial for subcellular localization of Gab1 and biological responses.

Cbl-transforming variants trigger a cascade of molecular alterations that lead to epithelial mesenchymal conversion.

Dispersal of epithelial cells is an important aspect of tumorigenesis, and invasion. Factors such as hepatocyte growth factor induce the breakdown of cell junctions and promote cell spreading and the dispersal of colonies of epithelial cells, providing a model system to investigate the biochemical signals that regulate these events. Multiple signaling proteins are phosphorylated in epithelial cells during hepatocyte growth factor-induced cell dispersal, including c-Cbl, a protooncogene docking protein with ubiquitin ligase activity. We have examined the role of c-Cbl and a transforming variant (70z-Cbl) in epithelial cell dispersal. We show that the expression of 70z-Cbl in Madin-Darby canine kidney epithelial cells resulted in the breakdown of cell-cell contacts and alterations in cell morphology characteristic of epithelial-mesenchymal transition. Structure-function studies revealed that the amino-terminal portion of c-Cbl, which corresponds to the Cbl phosphotyrosine-binding/Src homology domain 2, is sufficient to promote the morphological changes in cell shape. Moreover, a point mutation at Gly-306 abrogates the ability of the Cbl Src homology domain 2 to induce these morphological changes. Our results identify a role for Cbl in the regulation of epithelial-mesenchymal transition, including loss of adherens junctions, cell spreading, and the initiation of cell dispersal.