Novel functions of the polymeric Ig receptor: well beyond transport of immunoglobulins.

The polymeric Ig receptor (pIgR) ensures efficient secretion of polymeric IgA (pIgA) at mucosal surfaces. On basal to apical transport across epithelial cells, the pIgR extracellular domain is cleaved, releasing secretory component (SC) in association with pIgA. This finds its raison d'être in the recent observation that SC is directly involved in the protective function of secretory IgA. In addition, free SC exhibits scavenger properties with respect to enteric pathogens. However, although pIgR dedicates its life to mucosal protection, it also seems to permit pathogen entrance through the epithelial barrier. The multiple mechanisms that they are involved in make pIgR and SC instrumental to mucosal immunity.

Insights into shallow magmatic processes in large silicic magma bodies: the trace element record in the Fish Canyon magma body, Colorado

Highly evolved rhyolite glass plus near-solidus mineral assemblages in voluminous, dacitic, crystal-rich ignimbrites provide an opportunity to evaluate the late magmatic evolution of granodiorite batholiths. This study reports laser-ablation ICP-MS analyses of trace element concentrations in feldspars, hornblende, biotite, titanite, zircon, magnetite, and interstitial glass of the crystal-rich Fish Canyon Tuff. The high-silica rhyolite glass is characterized by relatively high concentrations of feldspar-compatible elements (e.g., 100 ppm Sr and 500 ppm Ba) and low concentrations of Y (< 7 ppm) and HREE (&SIM; 1 ppm Yb), hence high LREE/HREE (Ce/Yb > 40) compared to many well-studied high-silica rhyolite glasses and whole-rock compositions. Most minerals record some trace element heterogeneities, with, in particular, one large hornblende phenocryst showing four- to six-fold core-to-rim increases in Sr and Ba coupled with a decrease in Sc. The depletions of Y and HREE in the Fish Canyon glass relative to the whole-rock composition (concentrations in glass &SIM; 30% of those in whole rocks) reflect late crystallization of phases wherein these elements were compatible. As garnet is not stable at the low-P conditions at which the Fish Canyon magma crystallized, we show that a combination of modally abundant hornblende (&SIM; 4%) + titanite (&SIM; 0.5-1%) and the highly polymerized nature of the rhyolitic liquid led to Y and HREE depletions in melt. Relatively high Sr and Ba contents in glass and rimward Sr and Ba increases in euhedral, concentrically zoned hornblende suggest partial feldspar dissolution and a late release of these elements to the melt as hornblende was crystallizing, in agreement with textural evidence for feldspar (and quartz) resorption. Both observations are consistent with thermal rejuvenation of the magma body prior to eruption, during which the proportion of melt increased via feldspar and quartz dissolution, even as hydrous and accessory phases were crystallizing. Sr/Y in Fish Canyon glass (13-18) is lower than the typical ``adakitic'' value (> 40), confirming that high Sr/Y is a reliable indicator of high-pressure magma generation and/or differentiation wherein garnet is implicated.

A meta-analysis of the association of fracture risk and body mass index in women.

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m(2) ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25 kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m(2) was 0.87 (95% confidence interval [CI], 0.85-0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09-1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.

Body mass index, abdominal adiposity and blood pressure: consistency of their association across developing and developed countries.

BACKGROUND: Obesity is increasing worldwide because developing countries are adopting Western high-fat foods and sedentary lifestyles. In parallel, in many of them, hypertension is rising more rapidly, particularly with age, than in Western countries. OBJECTIVE: To assess the relationship between adiposity and blood pressure (BP) in a developing country with high average BP (The Seychelles, Indian Ocean, population mainly of African origin) in comparison to a developed country with low average BP (Switzerland, population mainly of Caucasian origin). DESIGN: Cross-sectional health examination surveys based on population random samples. SETTING: The main Seychelles island (Mahé) and two Swiss regions (Vaud-Fribourg and Ticino). SUBJECTS: Three thousand one hundred and sixteen adults (age range 35-64) untreated for hypertension. MEASUREMENTS: Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), systolic and diastolic blood pressure (SBP and DBP, mean of two measures). METHODS: Scatterplot smoothing techniques and gender-specific linear regression models. RESULTS: On average, SBP and DBP were found to increase linearly over the whole variation range of BMI, WHR and WC. A modest, but statistically significant linear association was found between each indicator of adiposity and BP levels in separate regression models controlling for age. The regression coefficients were not significantly different between the Seychelles and the two Swiss regions, but were generally higher in women than in men. For the latter, a gain of 1.7 kg/m(2) in BMI, of 4.5 cm in WC or of 3.4% in WHR corresponded to an elevation of 1 mmHg in SBP. For women, corresponding figures were 1.25 kg/m(2), 2.5 cm and 1.8% respectively. Regression coefficients for age reflected a higher effect of this variable on both SBP and DBP in the Seychelles than in Switzerland. CONCLUSION: These findings suggest a stable linear relation of adiposity with BP, independent of age and body fat distribution, across developed and developing countries. The more rapid increase of BP with age observed in the latter countries are likely to reflect higher genetic susceptibility and/or higher cumulative exposure to another risk factor than adiposity.

Inflammatory Markers and Incident Heart Failure Risk in Older Adults: The Health, Aging, and Body Composition Study

Background: Inflammation is associated with heart failure (HF) risk factors and also directly affects myocardial function. However, the association between inflammation and HF risk in older adults has not been adequately evaluated. Methods: The association of baseline serum concentrations of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF- ), and C-reactive protein (CRP) with incident HF was assessed with Cox proportional hazards models among 2610 older persons without prevalent HF enrolled in the Health, Aging, and Body Composition (Health ABC) Study (age, 73.6±2.9 years; 48.3% men; 59.6% white). Results: Median (interquartile range) baseline concentrations of IL-6, TNF- , and CRP were 1.80 (1.23, 2.76) pg/mL, 3.14 (2.41, 4.06) pg/mL, and 1.64 (0.99, 3.04) µg/mL, respectively. On follow-up (median, 9.4 years), 311 participants (11.9%) developed HF. In models controlling for clinical predictors of HF and incident coronary heart disease, doubling of IL-6, TNF- , and CRP concentrations was associated with 34% (95% CI, 18 -52%; P<.001), 33% (95% CI, 9 - 63%; P=.006), and 13% (95% CI, 3-24%; P=.01) increase in HF risk, respectively. In models including all 3 markers, IL-6 and TNF- , but not CRP, remained significant. Findings were similar across sex and race. Post-HF ejection fraction (EF) was available in 239 (76.8%) cases. When only cases with preserved EF were considered (n=105), IL-6 (HR per doubling, 1.57; 95% CI, 1.28 -1.94; P<.001), TNF- (HR per doubling, 1.59; 95% CI, 1.12-2.26; P=.01), and CRP (HR per doubling, 1.23; 95% CI, 1.05-1.44; P=.01) were all associated with HF risk in adjusted models. In contrast, when only cases with reduced EF (n=134) were considered, only IL-6 attained marginal significance in adjusted models (HR per doubling, 1.20; 95% CI, 0.99 -1.46; P=.06). Participants with 2 or 3 markers above median had pronounced HF risk in adjusted models (HR, 1.66; 95% CI, 1.12-2.46; P=.01; and HR, 1.76; 95% CI, 1.16 -2.65; P=.007, respectively). Addition of IL-6 to the clinical Health ABC HF model improved discrimination (C index from 0.717 to 0.734; P=.001) and fit (decreased Bayes information criterion by 17.8; P<.001). Conclusions: Inflammatory markers are associated with HF risk among older adults and may improve HF risk stratification.

Influences of body weight, body composition, and substrate oxidation rate on resting postabsorptive glucose production and gluconeogenesis.

OBJECTIVE: To determine the influence of body weight, fat mass, and fat distribution on resting endogenous glucose production in healthy lean and overweight individuals. DESIGN: measurements were performed in the resting postabsorptive state in individuals receiving an unrestricted diet. SETTING: Institute of Physiology of Lausanne University. MEASUREMENTS: resting post absorptive glucose production, glycogenolysis and gluconeogenesis; resting energy expenditure and net substrate oxidation. RESULTS: Endogenous glucose production was positively correlated with body weight, lean body mass, energy expenditure and carbohydrate oxidation. Gluconeogenesis was positively correlated with net lipid oxidation and energy expenditure, and negatively correlated with net carbohydrate oxidation. No correlation with body fat or fat distribution was observed. CONCLUSIONS: Gluconeogenesis shows a large interindividual variability. Net lipid oxidation and not body fat appears to be a major determinant of gluconeogenesis.

Standardisation of the waist circumference (WC) for each range of body mass index (BMI) in adult outpatients attended to in Endocrinology and Nutrition departments

By this study we seek the expectable range of waist circumference (WC) for every degree of body mass index (BMI), which will serve to studies targeting ascertaining the health risk. We studied 2,932 patients (39.6% men and 60.4% women, between 18 and 96 years ) of the same ethnic group who consecutively attended outpatient departments of our clinics between 2000 and 2004. BMI correlated linearly with the WC (cc: 0.85; p < 0.001). The men, the obese, and diabetics were older (p < 0.001). BMI was greater in women and WC in men. The women had a greater WC if they had diabetes (p < 0.01), being equal to diabetic males. The men had greater WC when they had diabetes (p < 0.001). Waist at risk was detected (men > or = 102 cm and women > or = 88 cm) in 94.3% of the obese, in 32.3% of overweight patients, in 3.8% of patients with BMI < 25, in 84.3% of diabetics, and in 72.6% of patients without diabetes. We made graphic standardisation of WC with regard to BMI, and we calculated the percentiles 10, 25, 50, 75 and 90, grouping in ranges of 2 kg/m(2) of BMI. The diabetic patients are grouped in ranges of 4 kg/m(2). As conclusion we present a standardisation of the WC measurement of patients attended to in our Endocrinology and Nutrition practices distributed in percentiles as a clinically usable tool to define the ranges of WC for every BMI value.

Intra-individual variation in body temperature and pectoral muscle size in nestling Alpine swifts Apus melba in response to an episode of inclement weather

The Alpine swift (Apus melba) forages on insects caught exclusively on the wing, implying that dependent nestlings face acute food shortage in periods of cold and rainy weather. Therefore, there should be strong selection on nestling swifts to evolve physiological strategies to cope with periods of undernutrition. We have investigated intra-individual changes in nestling pectoral muscle and body temperature in response to a 1-week period of inclement weather. The pectoral muscle is the largest reserves of proteins, and nestlings have to devote a large amount of energy in the maintenance of body temperature. The results show that nestling pectoral muscle size and body temperature were significantly reduced during the episode of inclement weather. Assuming that these physiological changes are adaptive, our study suggests that nestling swifts spare energy by a pronounced reduction (up to 18 degrees C) in body temperature and use proteins from the pectoral muscle as a source of extra energy to survive prolonged periods of fasting.

Synthesis and transport of creatine in the CNS: importance for cerebral functions.

J. Neurochem. (2010) 10.1111/j.1471-4159.2010.06935.x Abstract Apart of its well known function of 'energetic buffer' through the creatine/phosphocreatine/creatine kinase system allowing the regeneration of ATP, creatine has been recently suggested as a potential neuromodulator of even true neurotransmitter. Moreover, the recent discovery of primary creatine deficiency syndromes, due to deficiencies in l-arginine : glycine amidinotransferase or guanidinoacetate methyltransferase (the two enzymes allowing creatine synthesis) or in the creatine transporter, has shed new light on creatine synthesis, metabolism and transport, in particular in CNS which appears as the main tissue affected by these creatine deficiencies. Recent data suggest that creatine can cross blood-brain barrier but only with a poor efficiency, and that the brain must ensure parts of its needs in creatine by its own endogenous synthesis. Finally, the recent years have demonstrated the interest to use creatine as a neuroprotective agent in a growing number of neurodegenerative diseases, including Parkinson's and Huntington's diseases. This article aims at reviewing the latest data on creatine metabolism and transport in the brain, in relation to creatine deficiencies and to the potential use of creatine as neuroprotective molecule. Emphasis is also given to the importance of creatine for cerebral function.

Body context and posture affect mental imagery of hands.

Different visual stimuli have been shown to recruit different mental imagery strategies. However the role of specific visual stimuli properties related to body context and posture in mental imagery is still under debate. Aiming to dissociate the behavioural correlates of mental processing of visual stimuli characterized by different body context, in the present study we investigated whether the mental rotation of stimuli showing either hands as attached to a body (hands-on-body) or not (hands-only), would be based on different mechanisms. We further examined the effects of postural changes on the mental rotation of both stimuli. Thirty healthy volunteers verbally judged the laterality of rotated hands-only and hands-on-body stimuli presented from the dorsum- or the palm-view, while positioning their hands on their knees (front postural condition) or behind their back (back postural condition). Mental rotation of hands-only, but not of hands-on-body, was modulated by the stimulus view and orientation. Additionally, only the hands-only stimuli were mentally rotated at different speeds according to the postural conditions. This indicates that different stimulus-related mechanisms are recruited in mental rotation by changing the bodily context in which a particular body part is presented. The present data suggest that, with respect to hands-only, mental rotation of hands-on-body is less dependent on biomechanical constraints and proprioceptive input. We interpret our results as evidence for preferential processing of visual- rather than kinesthetic-based mechanisms during mental transformation of hands-on-body and hands-only, respectively.

Insights into the transcriptome of oenocytes from Aedes aegypti pupae

Oenocytes are ectodermic cells present in the fat body of several insect species and these cells are considered to be analogous to the mammalian liver, based on their role in lipid storage, metabolism and secretion. Although oenocytes were identified over a century ago, little is known about their messenger RNA expression profiles. In this study, we investigated the transcriptome of Aedes aegypti oenocytes. We constructed a cDNA library from Ae. aegypti MOYO-R strain oenocytes collected from pupae and randomly sequenced 687 clones. After sequences editing and assembly, 326 high-quality contigs were generated. The most abundant transcripts identified corresponded to the cytochrome P450 superfamily, whose members have roles primarily related to detoxification and lipid metabolism. In addition, we identified 18 other transcripts with putative functions associated with lipid metabolism. One such transcript, a fatty acid synthase, is highly represented in the cDNA library of oenocytes. Moreover, oenocytes expressed several immunity-related genes and the majority of these genes were lysozymes. The transcriptional profile suggests that oenocytes play diverse roles, such as detoxification and lipid metabolism, and increase our understanding of the importance of oenocytes in Ae. aegypti homeostasis and immune competence.

Characterization and binding affinities of SmLANP: a new Schistosoma mansoni member of the ANP32 family of regulatory proteins.

Members of the leucine-rich repeat protein family are involved in diverse functions including protein phosphatase 2-inhibition, cell cycle regulation, gene regulation and signalling pathways. A novel Schistosoma mansoni gene, called SmLANP, presenting homology to various genes coding for proteins that belong to the super family of leucine-rich repeat proteins, was characterized here. SmLANP was 1184bp in length as determined from cDNA and genomic sequences and encoded a 296 amino acid open reading frame that spanning from 6 to 894bp. The predicted amino acid sequence had a calculated molecular weight of 32kDa. Analysis of the predicted sequence indicated the presence of 3 leucine-rich domains (LRR) located in the N-terminal region and an aspartic acid rich region in the C-terminal end. SmLANP transcript is expressed in all stages of the S. mansoni life cycle analyzed, exhibiting the highest expression level in males. The SmLANP protein was expressed in a GST expression system and antibodies raised in mice against the recombinant protein. By immunolocalization assay, using adult worms, it was shown that the protein is mainly present in the cell nucleus through the whole body and strongly expressed along the tegument cell body nuclei of adult worms. As members of this family are usually involved in protein-protein interaction, a yeast two hybrid assay was conducted to identify putative binding partners for SmLANP. Thirty-six possible partners were identified, and a protein ATP synthase subunit alpha was confirmed by pull down assays, as a binding partner of the SmLANP protein.

A comparative study of fat body morphology in five mosquito species

The insect fat body plays major roles in the intermediary metabolism, in the storage and transport of haemolymph compounds and in the innate immunity. Here, the overall structure of the fat body of five species of mosquitoes (Aedes albopictus, Aedes fluviatilis, Culex quinquefasciatus, Anopheles aquasalis and Anopheles darlingi) was compared through light, scanning and transmission electron microscopy. Generally for mosquitoes, the fat body consists of lobes projecting into the haemocoel and is formed by great cell masses consisting of trophocytes and oenocytes. Trophocytes are rich in lipid droplets and protein granules. Interestingly, brown pigment granules, likely ommochromes, were found exclusively in the trophocytes located within the thorax and near the dorsal integument of Anopheles, which is suggestive of the role these cells play in detoxification via ommochrome storage. This study provides a detailed comparative analysis of the fat body in five different mosquito species and represents a significant contribution towards the understanding of the structural-functional relationships associated with this organ.

Determinants of non- response to a second assessment of lifestyle factors and body weight in the EPIC-PANACEA study.

BACKGROUND This paper discusses whether baseline demographic, socio-economic, health variables, length of follow-up and method of contacting the participants predict non-response to the invitation for a second assessment of lifestyle factors and body weight in the European multi-center EPIC-PANACEA study. METHODS Over 500.000 participants from several centers in ten European countries recruited between 1992 and 2000 were contacted 2-11 years later to update data on lifestyle and body weight. Length of follow-up as well as the method of approaching differed between the collaborating study centers. Non-responders were compared with responders using multivariate logistic regression analyses. RESULTS Overall response for the second assessment was high (81.6%). Compared to postal surveys, centers where the participants completed the questionnaire by phone attained a higher response. Response was also high in centers with a short follow-up period. Non-response was higher in participants who were male (odds ratio 1.09 (confidence interval 1.07; 1.11), aged under 40 years (1.96 (1.90; 2.02), living alone (1.40 (1.37; 1.43), less educated (1.35 (1.12; 1.19), of poorer health (1.33 (1.27; 1.39), reporting an unhealthy lifestyle and who had either a low (<18.5 kg/m2, 1.16 (1.09; 1.23)) or a high BMI (>25, 1.08 (1.06; 1.10); especially ≥30 kg/m2, 1.26 (1.23; 1.29)). CONCLUSIONS Cohort studies may enhance cohort maintenance by paying particular attention to the subgroups that are most unlikely to respond and by an active recruitment strategy using telephone interviews.