Different behaviour of mouse-human chimeric antibody F(ab')2 fragments of IgG1, IgG2 and IgG4 sub-class in vivo.

Mouse-human chimeric monoclonal antibodies (MAbs) of 3 different human IgG sub-classes directed against carcinoembryonic antigen (CEA) have been produced in SP-0 cells transfected with genomic chimeric DNA. F(ab')2 fragments were obtained by pepsin digestion of the purified chimeric MAbs of human IgG1, IgG2 and IgG4 sub-class and of parental mouse MAb IgG1. The 4 F(ab')2 fragments exhibit similar molecular weight by SDS-PAGE. They were labelled with 125I or 131I and high binding (80 to 87%) to purified unsolubilized CEA was observed. In vivo, double labelling experiments indicate that the longest biological half-life and the highest tumour-localization capacity is obtained with F(ab')2 from chimeric MAb of human IgG2 sub-class, whereas F(ab')2 from chimeric MAb IgG4 give very low values for these 2 parameters. F(ab')2 from chimeric MAb IgG1 and from parental mouse MAb yield intermediate results in vivo. Our findings should help to select the appropriate human IgG sub-class to produce chimeric or reshaped MAb F(ab')2 to be used for tumour detection by immunoscintigraphy and for radioimmunotherapy.

Fertility discourse in parental leave policies' media coverage : a frame analysis of French-speaking Swiss press articles from 1999 to 2009

This paper analyses the media coverage of parental leave policies (parental and paternity leaves) in Swiss French-speaking press articles from 1999 to 2009. Switzerland is one of the rare European countries which has no statutory parental or paternity leave. The aim is to describe the mediatisation of these policies and to analyse the arguments in favour and against their implementation. We investigate the status of a fertility frame - the mobilisation of discourse relating to fertility issues - among the various arguments used to justify or reject parental leave policies. We proceed with a content analysis of 579 press articles, as well as a frame analysis on a subset in which parental leave policies are the central theme (N=206). Results show that paternity leave is the predominant public issue addressed in the dataset. A mediatisation peak was reached in 2007, following an initiative of a member of the Federal executive to implement a short paternity leave. Parental leave policies are predominantly represented in a positive light. The main positive frame is economic, in which leaves are represented as serving the interests of companies. Involved fatherhood and gender equality are also frequently mentioned as positive frames. The fertility frame is only moderately used in articles covering Swiss news on paternity leaves. Conversely, the fertility frame is largely mobilised in articles covering parental leave in other countries. We discuss some interpretations of this discrepancy and suggest future avenues of research on parental leave policies in Switzerland.

Assessment of parental discipline in daily life.

The use of ecological momentary assessment (EMA) for studying parenting has been rare. We examined the psychometric properties and structural validity of an EMA Parenting Scale based on 32 mothers' reports of their parenting over a period of 10 consecutive days, and explored the acceptance of the scale and compliance with the procedure. The results suggested that the EMA Parenting Scale was well accepted for the assessment of daily parenting, and that it consistently captured the overreactive and lax dimensions of parenting across different episodes of child misbehavior. Moreover, multilevel analyses suggested that the scale was sensitive to change across different parenting episodes, and that it reliably assessed the dimensions at both the personal and situational levels. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Low molecular weight carboxylic acids in oxidizing porphyry copper tailings

The distribution of low molecular weight carboxylic acids (LMWCA) was investigated in pore water profiles from two porphyry copper tailings impoundments in Chile (Piuquenes at La Andina and Cauquenes at El Teniente mine). The objectives of this study were (1) to determine the distribution of LMWCA, which are interpreted to be the metabolic byproducts of the autotroph microbial community in this low organic carbon system, and (2) to infer the potential role of these acids in cycling of Fe and other elements in the tailings impoundments. The speciation and mobility of iron, and potential for the release of H+ via hydrolysis of the ferric iron, are key factors in the formation of acid mine drainage in sulfidic mine wastes. In the low-pH oxidation zone of the Piuquenes tailings, Fe(III) is the dominant iron species and shows high mobility. LMWCA, which occur mainly between the oxidation front down to 300 cm below the tailings surface at both locations (e.g., max concentrations of 0.12 mmol/L formate, 0.17 mmol/L acetate, and 0.01 mmol/L pyruvate at Piuquenes and 0.14 mmol/L formate, 0.14 mmol/L acetate, and 0.006 mmol/L pyruvate at Cauquenes), are observed at the same location as high Fe concentrations (up to 71.2 mmol/L Fe(II) and 16.1 mmol/L Fe(III), respectively). In this zone, secondary Fe(111) hydroxides are depleted. Our data suggest that LMWCA may influence the mobility of iron in two ways. First, complexation of Fe(III), through formation of bidentate Fe(III)-LMWCA complexes (e.g., pyruvate, oxalate), may enhance the dissolution of Fe(III) (oxy)hydroxides or may prevent precipitation of Fe(III) (oxy)hydroxides. Soluble Fe(III) chelate complexes which may be mobilized downward and convert to Fe(II) by Fe(III) reducing bacteria. Second, monodentate LMWCA (e.g., acetate and formate) can be used by iron-reducing bacteria as electron donors (e.g., Acidophilum spp.), with ferric iron as the electron acceptor. These processes may, in part, explain the low abundances of secondary Fe(III) hydroxide precipitates below the oxidation front and the high concentrations of Fe(II) observed in the pore waters of some low-sulfide systems. The reduction of Fe(III) and the subsequent increase of iron mobility and potential acidity transfer (Fe(II) oxidation can result in the release of H+ in an oxic environment) should be taken in account in mine waste management strategies.

Seed-specific silencing of OsMRP5 reduces seed phytic acid and weight in rice.

Phytic acid (PA) is poorly digested by humans and monogastric animals and negatively affects human/animal nutrition and the environment. Rice mutants with reduced PA content have been developed but are often associated with reduced seed weight and viability, lacking breeding value. In the present study, a new approach was explored to reduce seed PA while attaining competitive yield. The OsMRP5 gene, of which mutations are known to reduce seed PA as well as seed yield and viability, was down-regulated specifically in rice seeds by using an artificial microRNA driven by the rice seed specific promoter Ole18. Seed PA contents were reduced by 35.8-71.9% in brown rice grains of transgenic plants compared to their respective null plants (non-transgenic plants derived from the same event). No consistent significant differences of plant height or number of tillers per plant were observed, but significantly lower seed weights (up to 17.8% reduction) were detected in all transgenic lines compared to null plants, accompanied by reductions of seed germination and seedling emergence. It was observed that the silencing of the OsMRP5 gene increased the inorganic P (Pi) levels (up to 7.5 times) in amounts more than the reduction of PA-P in brown rice. This indicates a reduction in P content in other cellular compounds, such as lipids and nucleic acids, which may affect overall seed development. Put together, the present study demonstrated that seed specific silencing of OsMRP5 could significantly reduce the PA content and increase Pi levels in seeds; however, it also significantly lowers seed weight in rice. Discussions were made regarding future directions towards producing agronomically competitive and nutritionally valuable low PA rice.

Association between foot growth and musculoskeletal loading in children with Prader-Willi syndrome before and during growth hormone treatment

OBJECTIVE: To explore how foot growth relates to musculoskeletal loading in children with Prader-Willi syndrome (PWS). STUDY DESIGN: In 37 children with PWS, foot length (FL) before and after 6 years of growth hormone therapy (GHT) was retrospectively evaluated with parental and sibling's FL, height, and factors reflecting musculoskeletal loading, such as weight for height (WfH), lean body mass (LBM; dual energy X-ray absorptiometry, deuterium labeled water), physical activity (accellerometry), and walk age. Because of the typically biphasic evolution of body mass and the late walk age in PWS, 2 age groups were separated (group 1, >2.5 years; group 2, < or =2.5 years). RESULTS: Children with PWS normalized height, but not FL after 6 years of GHT. Parental FL correlation with PWS's FL was lower than with sibling's FL. In group 1, FL positively correlated with WfH, LBM, and physical activity. In group 2, FL negatively correlated with age at onset of independent ambulation. Foot catch-up growth with GHT was slower in group 2 compared with group 1. CONCLUSION: In PWS, FL is positively associated with musculoskeletal loading. Small feet in children with PWS before and during long-term GHT may be more than just another dysmorphic feature, but may possibly reflect decreased musculoskeletal loading influencing foot growth and genetic and endocrine factors.

Psychotropic drug-induced weight gain and other metabolic complications in a Swiss psychiatric population.

PURPOSE: To describe the weight gain-related side-effects of psychotropic drugs and their consequences on metabolic complications (hypercholesterolemia, obesity) in a Swiss cohort of psychiatric patients. METHOD: This cross-sectional observational study was performed in an out-patient psychiatric division with patients having received for more than 3 months the following drugs: clozapine, olanzapine, quetiapine, risperidone, lithium, and/or valproate. Clinical measures and lifestyle information (smoking behaviour, physical activity) were recorded. RESULTS: 196 inclusions were completed. Weight gain (≥10% of initial weight) following drug treatment was reported in 47% of these patients. Prevalence of obesity (BMI ≥ 30), hypercholesterolemia (≥6.2 mmol/L) and low HDL-cholesterol (<1.0 mmol/L in men, <1.3 mmol/L in women) were present in 38%, 21%, and 27% of patients, respectively. A higher standardised dose, an increase of appetite following medication introduction, the type of medication (clozapine or olanzapine > quetiapine or risperidone > lithium or valproate), and the gender were shown to be significantly associated with evolution of BMI. CONCLUSION: High prevalence of obesity and hypercholesterolemia was found in an out-patient psychiatric population and confirms drug-induced weight gain complications during long-term treatment. The results support the recently published recommendations of monitoring of metabolic side-effects during treatment with atypical antipsychotics. Moreover, the weight gain predictors found in the present study could help to highlight patients with special health care management requirement.

Early parenteral lipids and growth velocity in extremely-low-birth-weight infants.

BACKGROUND & AIMS: Whether early parenteral lipids improve postnatal growth of preterm neonates remains unclear. We aimed to assess the effects of parenteral lipids on growth velocity in extremely-low-birth-weight infants. METHODS: This retrospective cohort study included 121 extremely-low-birth-weight infants. The associations between parenteral lipids (cumulative intakes during the first week and delays in their introduction) and growth velocities (weight, head circumference and length) up to 28 days of life and to 36 weeks of corrected age were analysed using uni- and multivariate linear regression. RESULTS: Univariate analyses showed a significant positive association between the cumulative intakes of parenteral lipids during the first week and i) weight gain up to day 28; ii) weight gain up to 36 weeks of corrected age; iii) head circumference growth up to day 28. There was a negative correlation between the delay in parenteral lipid introduction and weight gain up to day 28. In multivariate analyses, the association between the cumulative intakes of parenteral lipids and weight gain up to 28 days was independent of gestational age at birth, birth weight, sex, smallness for gestational age, and enteral intakes (regression coefficient: 0.19; 95% CI: 0.01-0.38) and, up to 36 weeks, independent of gestational age, birth weight, sex, smallness for gestational age and parenteral glucose and amino acids (0.16; 95% CI: 0.04-0.27). CONCLUSIONS: Parenteral lipids during the first week were positively associated with weight gain in extremely-low-birth-weight infants and could improve early nutritional support of preterm neonates.

MHC-genotype of progeny influenced by parental infection.

In a previous series of in vitro fertilization experiments with mice we found non-random combination of major histocompatibility complex (MHC) haplotypes in the very early embryos. Our results suggested that two selection mechanisms were operating: (i) the eggs selected specific sperm; and (ii) the second meiotic division in the eggs was influenced by the type of sperm that entered the egg. Furthermore, the proportion of MHC-heterozygous embryos varied over time, suggesting that non-random fertilization was dependent on an external factor that changed over time. As a higher frequency of heterozygous individuals correlated with an uncontrolled epidemic by MHV (mouse hepatitis virus), we suggested that MHV-infection might have influenced the outcome of fertilization. Here, we present an experiment that tests this hypothesis. We infected randomly chosen mice with MHV and sham-infected control mice five days before pairing. We recovered the two-cell embryos from the oviduct, cultured them until the blastocyst stage, and determined the genotype of each resulting blastocyst by polymerase chain reaction. We found the pattern that we expected from our previous experiments: virus-infected mice produced more MHC-heterozygous embryos than sham-infected ones. This suggests that parents are able to promote specific combinations of MHC-haplotypes during fertilization according to the presence or absence of a viral infection.

Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide.

AIMS/HYPOTHESIS: Intramyocellular lipids, including diacylglycerol (DAG) and ceramides, have been linked to insulin resistance. This randomised repeated-measures study examined the effects of diet-induced weight loss (DIWL) and aerobic exercise (EX) on insulin sensitivity and intramyocellular triacylglycerol (IMTG), DAG and ceramide. METHODS: Sixteen overweight to obese adults (BMI 30.6 ± 0.8; 67.2 ± 4.0 years of age) with either impaired fasting glucose, or impaired glucose tolerance completed one of two lifestyle interventions: DIWL (n = 8) or EX (n = 8). Insulin sensitivity was determined using hyperinsulinaemic-euglycaemic clamps. Intramyocellular lipids were measured in muscle biopsies using histochemistry and tandem mass spectrometry. RESULTS: Insulin sensitivity was improved with DIWL (20.6 ± 4.7%) and EX (19.2 ± 12.9%). Body weight and body fat were decreased by both interventions, with greater decreases in DIWL compared with EX. Muscle glycogen, IMTG content and oxidative capacity were all significantly (p < 0.05) decreased with DIWL and increased with EX. There were decreases in DAG with DIWL (-12.4 ± 14.6%) and EX (-40.9 ± 12.0%). Ceramide decreased with EX (-33.7 ± 11.2%), but not with DIWL. Dihydroceramide was decreased with both interventions. Sphingosine was decreased only with EX. Changes in total DAG, total ceramides and other sphingolipids did not correlate with changes in glucose disposal. Stearoyl-coenzyme A desaturase 1 (SCD1) content was decreased with DIWL (-19.5 ± 8.5%, p < 0.05), but increased with EX (19.6 ± 7.4%, p < 0.05). Diacylglycerol acyltransferase 1 (DGAT1) was unchanged with the interventions. CONCLUSIONS/INTERPRETATION: Diet-induced weight loss and exercise training both improved insulin resistance and decreased DAG, while only exercise decreased ceramides, despite the interventions having different effects on IMTG. These alterations may be mediated through differential changes in skeletal muscle capacity for oxidation and triacylglycerol synthesis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00766298.