To evaluate the influence of breast-feeding on the body mass index (BMI) growth trajectory from birth through 13 years of age among offspring of diabetic pregnancies (ODP) and offspring of ...non-diabetic pregnancies (ONDP) participating in the Exploring Perinatal Outcomes Among Children Study.
There were 94 ODP and 399 ONDP who had multiple BMI measures obtained from birth throughout childhood. A measure of breast milk-months was derived from maternal self-report to categorize breast-feeding status as adequate (≥6 breast milk-months) or low (<6 breast milk-months). Mixed linear-effects models were constructed to assess the impact of breast-feeding on the BMI growth curves during infancy (birth to 27 months) and childhood (27 months to 13 years).
ODP who were adequately breast-fed had a slower BMI growth trajectory during childhood (P=0.047) and slower period-specific growth velocity with significant differences between 4 and 6 years of age (P=0.03) and 6 to 9 years of age (P=0.01) compared with ODP with low breast-feeding. A similar pattern was seen in the ONDP, with adequate breast-feeding associated with lower average BMI in infancy (P=0.03) and childhood (P=0.0002) and a slower growth trajectory in childhood (P=0.0002). Slower period-specific growth velocity was seen among the ONDP associated with adequate breast-feeding with significant differences between 12-26 months (P=0.02), 4-6 years (P=0.03), 6-9 years (P=0.0001) and 9-13 years of age (P<0.0001).
Our study provides novel evidence that breast-feeding is associated with long-term effects on childhood BMI growth that extend beyond infancy into early and late childhood. Importantly, these effects are also present in the high-risk offspring, exposed to overnutrition during pregnancy. Breast-feeding in the early postnatal period may represent a critical opportunity to reduce the risk of childhood obesity.
Aims/hypothesis To evaluate whether exposure to maternal gestational diabetes (GDM) is associated with adiposity and fat distribution in a multiethnic population of children. Methods Retrospective ...cohort study of 82 children exposed to maternal GDM and 379 unexposed youths 6-13 years of age with measured BMI, waist circumference, skinfold thickness, and visceral and subcutaneous abdominal fat. Results Exposure to maternal GDM was associated with higher BMI (p = 0.02), larger waist circumference (p = 0.004), more subcutaneous abdominal fat (p = 0.01) and increased subscapular to triceps skinfold thickness ratio (p = 0.01) in models adjusted for age, sex, race/ethnicity and Tanner stage. Adjustment for socioeconomic factors, birthweight and gestational age, maternal smoking during pregnancy and current diet and physical activity did not influence associations; however, adjustment for maternal pre-pregnancy BMI attenuated all associations. Conclusions/interpretation Exposure to maternal GDM is associated with increased overall and abdominal adiposity, and a more central fat distribution pattern in 6- to 13-year-old youths from a multi-ethnic population, providing further support for the fetal overnutrition hypothesis.
The importin‐alpha/beta heterodimer and the GTPase Ran play key roles in nuclear protein import. Importin binds the nuclear localization signal (NLS). Translocation of the resulting import ligand ...complex through the nuclear pore complex (NPC) requires Ran and is terminated at the nucleoplasmic side by its disassembly. The principal GTP exchange factor for Ran is the nuclear protein RCC1, whereas the major RanGAP is cytoplasmic, predicting that nuclear Ran is mainly in the GTP form and cytoplasmic Ran is in the GDP‐bound form. Here, we show that nuclear import depends on cytoplasmic RanGDP and free GTP, and that RanGDP binds to the NPC. Therefore, import might involve nucleotide exchange and GTP hydrolysis on NPC‐bound Ran. RanGDP binding to the NPC is not mediated by the Ran binding sites of importin‐beta, suggesting that translocation is not driven from these sites. Consistently, a mutant importin‐beta deficient in Ran binding can deliver its cargo up to the nucleoplasmic side of the NPC. However, the mutant is unable to release the import substrate into the nucleoplasm. Thus, binding of nucleoplasmic RanGTP to importin‐beta probably triggers termination, i.e. the dissociation of importin‐alpha from importin‐beta and the subsequent release of the import substrate into the nucleoplasm.
NLS proteins are transported into the nucleus by the importin α/β heterodimer. Importin α binds the NLS, while importin β mediates translocation through the nuclear pore complex. After translocation, ...RanGTP, whose predicted concentration is high in the nucleus and low in the cytoplasm, binds importin β and displaces importin α. Importin α must then be returned to the cytoplasm, leaving the NLS protein behind. Here, we report that the previously identified CAS protein mediates importin α re-export. CAS binds strongly to importin α only in the presence of RanGTP, forming an importin α/CAS/RanGTP complex. Importin α is released from this complex in the cytoplasm by the combined action of RanBP1 and RanGAP1. CAS binds preferentially to NLS-free importin α, explaining why import substrates stay in the nucleus.
RanGAP1 Induces GTPase Activity of Nuclear Ras-Related Ran Bischoff, F. Ralf; Klebe, Christian; Kretschmer, Jurgen ...
Proceedings of the National Academy of Sciences - PNAS,
03/1994, Volume:
91, Issue:
7
Journal Article, Conference Proceeding
Peer reviewed
Open access
The nuclear Ras-related protein Ran binds guanine nucleotide and is involved in cell cycle regulation. Models of the signal pathway predict Ran to be active as Ran-GTP at the initiation of S phase ...upon activation by the nucleotide exchange factor RCC1 and to be inactivated for the onset of mitosis by hydrolysis of bound GTP. Here a nuclear homodimeric 65-kDa protein, RanGAP1, is described, which we believe to be the immediate antagonist of RCC1. It was purified from HeLa cell lysates and induces GTPase activity of Ran, but not Ras, by more than 3 orders of magnitude. The Ran mutant Q69L, modeled after RasQ61L, which is unable to hydrolyze bound GTP, is insensitive to RanGAP1.
Microbial biomass, size and community structure along with an estimate of microbial activity and soil chemical parameters were determined at three depths in two soils (e.g. sandy loam Ultic Hapludalf ...and silt loam Mollic Hapludalf) replicated three times under one winter and summer season. Microbial biomass and community structure were estimated from phospholipid-PO
4 content and fatty acid methyl ester (FAME) measurements. Microbial activity and assimilative capacity were estimated using a
3
H
-acetate incorporation into phospholipids and by incubating the soil samples at the average winter and summer temperatures, 3 and 20
°C, respectively. We found that the size of the microbial biomass in both the surface and the subsurface soils was not significantly affected by the seasonal variation but activity increased by as much as 83% at the summer temperatures in the surface soil. We demonstrated using FAME analysis that for both soils seasonal changes in the subsurface microbial community occurred. These findings suggest that winter conditions will shift the population activity level in both the surface and subsurface systems and the biochemical structure of the community in the subsurface. In all cases, the inorganic chemical properties of the soil, as a function of season, remained constant. The greatly increased activity of microbial population at the higher temperature will favor the capacity of the system to utilize nutrients or organic materials that may enter soil. During low temperature seasons the capacity of either surface or subsurface soils to assimilate materials is generally diminished but the reduction reflects changes in metabolism and not a reduced biomass size.
A Novel Class of RanGTP Binding Proteins Görlich, Dirk; Dabrowski, Marylena; Bischoff, F. Ralf ...
The Journal of cell biology,
07/1997, Volume:
138, Issue:
1
Journal Article
Peer reviewed
Open access
The importin-α/β complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. Although Ran has been implicated also in a variety of other processes, ...such as cell cycle progression, a direct function of Ran has so far only been demonstrated for importin-mediated nuclear import. We have now identified an entire class of ∼20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-β. We have confirmed specific RanGTP binding for some of them, namely for two novel factors, RanBP7 and RanBP8, for CAS, Pse1p, and Msn5p, and for the cell cycle regulator Cse1p from Saccharomyces cerevisiae. We have studied RanBP7 in more detail. Similar to importin-β, it prevents the activation of Ran's GTPase by RanGAP1 and inhibits nucleotide exchange on RanGTP. RanBP7 binds directly to nuclear pore complexes where it competes for binding sites with importin-β, transportin, and apparently also with the mediators of mRNA and U snRNA export. Furthermore, we provide evidence for a Ran-dependent transport cycle of RanBP7 and demonstrate that RanBP7 can cross the nuclear envelope rapidly and in both directions. On the basis of these results, we propose that RanBP7 might represent a nuclear transport factor that carries an as yet unknown cargo, which could apply as well for this entire class of related RanGTP-binding proteins.
Highlights ► The fate of nanomaterials in soil is partially controlled by sorption to organic matter. ► Biological degradation of carbon nanomaterials may require abiotic surface activation. ► Solar ...radiation can alter the surface of C60 . ► Nanocomposites will be an important source of nanomaterials in the environment. ► Degradation patterns of nanocomposites are unknown.
Nucleocytoplasmic transport appears mediated by shuttling transport receptors that bind RanGTP as a means to regulate interactions with their cargoes. The receptor·RanGTP complexes are kinetically ...very stable with nucleotide exchange and GTP hydrolysis being blocked, predicting that a specific disassembly mechanism exists. Here we show in three cases receptor·RanGTP·RanBP1 complexes to be the key disassembly intermediates, where RanBP1 stimulates the off-rate at the receptor/RanGTP interface by more than two orders of magnitude. The transiently released RanGTP·RanBP1 complex is then induced by RanGAP to hydrolyse GTP, preventing the receptor to rebind RanGTP. The efficient release of importin β from RanGTP requires importin α, in addition to RanBP1.
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