Exercise Training and Weight Gain in Obese Pregnant Women: A Randomized Controlled Trial (ETIP Trial)

BackgroundThe effectiveness of exercise training for preventing excessive gestational weight gain (GWG) and gestational diabetes mellitus (GDM) is still uncertain. As maternal obesity is associated with both GWG and GDM, there is a special need to assess whether prenatal exercise training programs provided to obese women reduce the risk of adverse pregnancy outcomes. Our primary aim was to assess whether regular supervised exercise training in pregnancy could reduce GWG in women with prepregnancy overweight/obesity. Secondary aims were to examine the effects of exercise in pregnancy on 30 outcomes including GDM incidence, blood pressure, blood measurements, skinfold thickness, and body composition.ConclusionsIn this trial we did not observe a reduction in GWG among overweight/obese women who received a supervised exercise training program during their pregnancy. The incidence of GDM in late pregnancy seemed to be lower in the women randomized to exercise training than in the women receiving standard maternity care only. Systolic blood pressure in late pregnancy was also apparently lower in the exercise group than in the control group. These results indicate that supervised exercise training might be beneficial as a part of standard pregnancy care for overweight/obese women.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01243554","term_id":"NCT01243554"}}NCT01243554     

H?henverbreitung der V?gel

Ohne Zusammenfassung     

First fungus gnats of genus Manota Williston (Diptera: Mycetophilidae) from Japan

The genus Manota is recorded from Japan for the first time. Three new species, Manota satoyamanis, Manota indahae and Manota tunoae spp. nov., are described, based on specimens collected in an ecological sampling program of arthropods in the “satoyama” landscape of Ishikawa Prefecture. “Satoyama” represents the traditional rural landscape of Japan, which is characterized by a mosaic of secondary forests, plantations, ponds and rice paddy fields. The new species raise the number of Palearctic Manota species from five to eight.     

Regulatory Properties of ADP Glucose Pyrophosphorylase Are Required for Adjustment of Leaf Starch Synthesis in Different Photoperiods

Arabidopsis (Arabidopsis thaliana) leaves synthesize starch faster in short days than in long days, but the mechanism that adjusts the rate of starch synthesis to daylength is unknown. To understand this mechanism, we first investigated whether adjustment occurs in mutants lacking components of the circadian clock or clock output pathways. Most mutants adjusted starch synthesis to daylength, but adjustment was compromised in plants lacking the GIGANTEA or FLAVIN-BINDING, KELCH REPEAT, F BOX1 components of the photoperiod-signaling pathway involved in flowering. We then examined whether the properties of the starch synthesis enzyme adenosine 5′-diphosphate-glucose pyrophosphorylase (AGPase) are important for adjustment of starch synthesis to daylength. Modulation of AGPase activity is known to bring about short-term adjustments of photosynthate partitioning between starch and sucrose (Suc) synthesis. We found that adjustment of starch synthesis to daylength was compromised in plants expressing a deregulated bacterial AGPase in place of the endogenous AGPase and in plants containing mutant forms of the endogenous AGPase with altered allosteric regulatory properties. We suggest that the rate of starch synthesis is in part determined by growth rate at the end of the preceding night. If growth at night is low, as in short days, there is a delay before growth recovers during the next day, leading to accumulation of Suc and stimulation of starch synthesis via activation of AGPase. If growth at night is fast, photosynthate is used for growth at the start of the day, Suc does not accumulate, and starch synthesis is not up-regulated.Many plants store starch as a product of photosynthesis in leaves during day then degrade it to provide sugar for continued metabolism and growth at night. It is well established that rates of starch synthesis adjust to changes in daylength. Adjustments occur in plants acclimated to different daylengths: the shorter the day, the greater the proportion of photosynthate allocated to starch and hence available for metabolism at night (Chatterton and Silvius, 1979; Baysdorfer and Robinson, 1985; Hewitt et al., 1985; Lorenzen and Ewing, 1992; Lu et al., 2005; Gibon et al., 2009; Sulpice et al., 2014). In Arabidopsis (Arabidopsis thaliana), starch synthesis is also accelerated in the light period following a single, unexpected extension of the night (Gibon et al., 2004a). The mechanisms that adjust the rate of starch synthesis to daylength are not known. Neither the nature of the signals from daylength nor the manner in which they influence starch synthesis are understood, and it is not known whether the acclimation of the rate of starch synthesis to different daylengths involves the same mechanisms as its immediate adjustment following an unexpected extension of the night.By contrast, the short-term control of starch synthesis is well understood. Partitioning of photosynthate into starch in the chloroplast is largely determined by the balance between the rate of photosynthetic carbon assimilation and the rate of Suc synthesis. Assimilate for Suc synthesis is exported from the chloroplast as triose phosphate, in exchange for inorganic phosphate (Pi) released during its cytosolic conversion to Suc. The rate of Suc synthesis is regulated via action of Fru 2,6-bisphosphate on the cytosolic Fru 1,6-bisphosphatase and allosteric and posttranslational regulation of Suc phosphate synthase (Stitt and Quick, 1989; Stitt et al., 2010). If the rate of Suc synthesis falls, for example in response to feedback from decreased utilization by sink organs, the amount of Pi available for exchange with triose phosphate is decreased, leading to retention of a larger proportion of the triose phosphate in the chloroplast and its use for starch synthesis. Conversely, if the rate of photosynthetic carbon assimilation falls, for example as a result of shading or stomatal closure, the concentration of triose phosphate in the chloroplast tends to fall, and the rate of starch synthesis decreases. Thus, a change in either the rate of photosynthetic carbon assimilation or the rate of Suc synthesis can rapidly bring about a change in the amount of photosynthate allocated to starch synthesis.These short-term adjustments of starch synthesis are brought about by modulation of the activity of adenosine 5′-diphosphate-glucose pyrophosphorylase (AGPase). This enzyme catalyzes the first committed step in starch biosynthesis: the synthesis of ADP-Glc and pyrophosphate from ATP and Glc 1-P. It is composed of large and small subunits and is subject to several levels of posttranslational regulation. The allosteric properties of the enzyme potentially allow it to regulate flux into starch in response to the rate of cytosolic Suc synthesis. High levels of triose phosphate in the chloroplast result in high 3-phosphoglyceraldehyde (3-PGA) levels, which activate the enzyme. Low levels of triose phosphate result in low 3-PGA and high Pi levels, which inhibit the enzyme (Heldt et al., 1977; Stitt et al., 1987). AGPase is also activated in the light and by sugars through reduction via NADP-thioredoxin reductase C and the thioredoxin Trx f1, which causes the loss of a disulfide bond between the two small subunits. Redox activation greatly increases the sensitivity of the enzyme to allosteric regulation by 3-PGA and Pi (Preiss, 1988; Kavakli et al., 2002; Tiessen et al., 2002; Hendriks et al., 2003; Michalska et al., 2009; Thormählen et al., 2013). Both large and small subunits are reported to be phosphorylated (Reiland et al., 2009, 2011; Nakagami et al., 2010; Umezawa et al., 2013; Wu et al., 2013), but the functional significance of these modifications is not known. Flux control analysis using Arabidopsis mutants with reduced activities of starch biosynthetic enzymes shows that AGPase can exert strong control over the rate of starch synthesis during photosynthesis, although the degree of control varies with environmental conditions (Neuhaus and Stitt, 1990; Sun et al., 1999; Hädrich et al., 2011). These mechanisms enable coordinated control of the use of Calvin-Benson cycle metabolites for starch and Suc synthesis, preventing the depletion of cycle intermediates and the inhibition of photosynthesis.It is not clear whether the mechanism that mediates short-term regulation of starch synthesis forms part of the unknown mechanism(s) by which starch synthesis is adjusted to daylength. One possibility is that a daylength-dependent signal sets an underlying default level of partitioning between Suc and starch or a target quantity of starch to be accumulated by the anticipated end of the day and that the short-term control described above operates on top of this default setting. We showed recently that the rate of starch degradation in leaves at night is controlled in part by the circadian clock (Graf et al., 2010; Scialdone et al., 2013): perhaps an analogous, clock-based mechanism ensures that sufficient starch is synthesized during the day to meet the carbon demands of the plant during the night. Daylength-dependent signals might affect partitioning through modulation of the abundance or properties of key enzymes of starch and/or Suc synthesis. Consistent with this idea, plants grown in short days have higher maximum catalytic activities of AGPase relative to Suc phosphate synthase than plants grown in long days (Gibon et al., 2009; Sulpice et al., 2014), due, in particular, to a rise of AGPase activity and protein before dawn in short but not in long days (Gibon et al., 2004b). Modulation of the redox sensitivity of AGPase can also affect partitioning: complementation of an AGPase-deficient Arabidopsis mutant with a mutagenized AGPase that is redox insensitive and mimics a constitutively redox-activated enzyme resulted in faster rates of starch accumulation in short days and low irradiance and the maintenance of slightly higher starch levels throughout the diel cycle in long day or high light regimes. However, these plants were still able to adjust the rate of starch synthesis in response to changes in daylength, indicating that redox modulation of activity is not essential for the response to photoperiod (Hädrich et al., 2012).A second possibility is that the general relationship between starch synthesis and daylength is determined indirectly by daylength-dependent variation in the demand for photosynthate for growth. We showed recently that the temporal pattern of growth varies with daylength (Sulpice et al., 2014): our data are consistent with growth rates at night and at the start of the day being high in long days but lower in short days. Differences in growth rate impose different demands for Suc, hence different rates of Suc synthesis at the start of the day. Such differences are expected to influence the rate of starch synthesis via the AGPase-dependent mechanism described above.To shed further light on mechanisms that gear the rate of starch synthesis to daylength in Arabidopsis, we first examined the importance for this relationship of components of the circadian clock and related photoperiod-signaling pathways. We then examined whether the properties of AGPase that are crucial for adjustment of starch synthesis over a single photoperiod are also important for the relationship between starch synthesis and the length of the photoperiod. This was achieved by replacing the endogenous Arabidopsis AGPase with a deregulated bacterial AGPase and examining the impact upon the response of starch synthesis to daylength and to an unexpected extension of the night.     

Arabidopsis Coordinates the Diurnal Regulation of Carbon Allocation and Growth across a Wide Range of Photoperiods

In short photoperiods, plants accumulate starch more rapidly in the light and degrade it more slowly at night, ensuring that their starch reserves last until dawn. To investigate the accompanying changes in the timing of growth, Arabidopsis was grown in a range of photoperiods and analyzed for rosette biomass, photosynthesis, respiration, ribosome abundance, polysome loading, starch, and over 40 metabolites at dawn and dusk. The data set was used to model growth rates in the daytime and night, and to identify metabolites that correlate with growth. Modeled growth rates and polysome loading were high in the daytime and at night in long photoperiods, but decreased at night in short photoperiods. Ribosome abundance was similar in all photoperiods. It is discussed how the amount of starch accumulated in the light period, the length of the night, and maintenance costs interact to constrain growth at night in short photoperiods, and alter the strategy for optimizing ribosome use. Significant correlations were found in the day- time and the night between growth rates and the levels of the sugar-signal trehalose 6-phosphate and the amino acid biosynthesis intermediate shikimate, identifying these metabolites as hubs in a network that coordinates growth with diurnal changes in the carbon supply.     

Manufacturing and <Emphasis Type="Italic">in vivo</Emphasis> inner ear visualization of MRI traceable liposome nanoparticles encapsulating gadolinium

Background  

Treatment of inner ear diseases remains a problem because of limited passage through the blood-inner ear barriers and lack of control with the delivery of treatment agents by intravenous or oral administration. As a minimally-invasive approach, intratympanic delivery of multifunctional nanoparticles (MFNPs) carrying genes or drugs to the inner ear is a future therapy for treating inner ear diseases, including sensorineural hearing loss (SNHL) and Meniere's disease. In an attempt to track the dynamics and distribution of nanoparticles in vivo, here we describe manufacturing MRI traceable liposome nanoparticles by encapsulating gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) (abbreviated as LPS+Gd-DOTA) and their distribution in the inner ear after either intratympanic or intracochlear administration.     

Effect of iodine on early stage thyroid autonomy

Thyroid autonomy is a frequent cause of thyrotoxicosis in regions with iodine deficiency. Epidemiological data suggest that iodide may influence the course of pre-existing thyroid autonomy. Making use of FRTL-5 cells stably expressing a constitutively activating TSH receptor mutation as an in vitro model of thyroid autonomy, we investigated the impact of iodide on proliferation, function and changes in global gene expression. We demonstrate that iodine inhibits growth in TSHR WT and L629F mutant FRTL-5 cells and downregulates e.g. protocadherin cluster (Pcdha1-13) and thyroid responsive element (Thrsp). In addition functional genes e.g. iodotyrosine deiodinase (iyd) and oncogen junB are upregulated, while sodium-iodide-symporter (Nis) and thyroid peroxidase (Tpo) are downregulated by iodide. Iodide tunes down the biological activity of autonomous thyrocytes and may thus be of therapeutic benefit not only to prevent the occurrence of somatic TSHR mutations, causing thyroid autonomy, but also to slow down the development of clinically relevant disease.     

Solid-state circular dichroism and hydrogen bonding: absolute configuration of massarigenin A from Microsphaeropsis sp

Massarigenin A (1) and papyracillic acids A (2) and B (3) were isolated from the endophytic fungus Microsphaeropsis sp. Their structures were elucidated by multidimensional nuclear magnetic resonance spectroscopy; the structure of massarigenin A (1) was also confirmed by X-ray crystallography. The absolute configuration of massarigenin A (1) was established by means of circular dichroism (CD) spectroscopy and time-dependent density functional theory (TDDFT) calculations. The impact of intermolecular hydrogen bonds detected in the crystal packing of 1 on CD spectra measured in the solid state was also investigated.     

A comparison of exogenous promoter activity at the ROSA26 locus using a ΦiC31 integrase mediated cassette exchange approach in mouse ES cells

The activities of nine ubiquitous promoters (ROSA26, CAG, CMV, CMVd1, UbC, EF1α, PGK, chicken β-actin and MC1) have been quantified and compared in mouse embryonic stem cells. To avoid the high variation in transgene expression which results from uncontrolled copy number and chromosomal position effects when using random insertion based transgenic approaches, we have adopted a PhiC31 integrase mediated cassette exchange method for the efficient insertion of transgenes at single copy within a defined and well characterized chromosomal position, ROSA26. This has enabled the direct comparison of constructs from within the same genomic context and allows a systematic and quantitative assessment of the strengths of the promoters in comparison with the endogenous ROSA26 promoter. The behavior of these exogenous promoters, when integrated at ROSA26 in both sense and antisense orientations, reveals a large variation in their levels of activity. In addition, a subset of promoters, EF1α, UbC and CAG, show an increased activity in the sense orientation as a consequence of integration. Transient transfection experiments confirmed these observations to reflect integration dependent effects and also revealed significant differences in the behaviour of these promoters when delivered transiently or stably. As well as providing an important reference which will facilitate the choice of an appropriate promoter to achieve the desired level of expression for a specific research question, this study also demonstrates the suitability of the cassette exchange methodology for the robust and reliable expression of multiple variant transgenes in ES cells.     

Bioactive briarane diterpenoids from the South China Sea gorgonian Dichotella gemmacea

Six new briarane diterpenoids, gemmacolides T-Y (1-6), were isolated together with three known analogs, juncenolide J (7), praelolide (8), and junceellolide C (9), from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configuration was suggested based on biosynthetic considerations. In an in vitro bioassay, compounds 3 and 6 showed potent growth inhibition towards tumor cell lines of A549 and MG63, being stronger than the positive control of adriamycin. These compounds also exhibited weak antimicrobial activity against the bacterium Escherichia coli and the fungi Microbotryum violaceum and Septoria tritici.