Two‐Year Changes in Child Weight Status,Diet, and Activity by Neighborhood Nutrition and Physical Activity Environment

Objective

The aim of this study was to examine 2‐year changes in weight status and behaviors among children living in neighborhoods differing on nutrition and activity environments.

Methods

A prospective observational study, the Neighborhood Impact on Kids study, was conducted in King County, Washington, and San Diego County, California. Children 6 to 12 years old and a parent or caregiver completed Time 1 (n = 681) and Time 2 (n = 618) assessments. Children lived in neighborhoods characterized as “high/favorable” or “low/unfavorable” in nutrition and activity environments, respectively (four neighborhood types). Child BMI z score and overweight or obesity status were primary outcomes, with diet and activity behaviors as behavioral outcomes.

Results

After adjusting for sociodemographics and Time 1 values, children living in two of the three less environmentally supportive neighborhoods had significantly less favorable BMI z score changes (+0.11, 95% CI: 0.01‐0.21; + 0.12, 95% CI: 0.03‐0.21), and all three less supportive neighborhoods had higher overweight or obesity (relative risks, 1.41‐1.49; 95% CI: 1.13‐1.80) compared with children in the most environmentally supportive neighborhoods. Changes in daily energy intake and sedentary behavior by neighborhood type were consistent with observed weight status changes, with unexpected findings for physical activity.

Conclusions

More walkable and recreation‐supportive environments with better nutrition access were associated with better child weight outcomes and related behavior changes.     

Structural basis for inhibition of translation by the tumor suppressor Pdcd4

The tumor suppressor function of Programmed Cell Death 4 (Pdcd4) is achieved through interactions between Pdcd4 and components of the translation initiation complex, namely, the RNA helicase eIF4A and the scaffolding protein eIF4G. These interactions are mediated through two MA3 domains on the Pdcd4 molecule and result in inhibition of protein synthesis. We have solved the high-resolution crystal structure of the C-terminal MA3 (cMA3) domain of Pdcd4 in several crystal forms and demonstrated its similarity to the MA3 domain of eIF4G. As predicted by the structure, the cMA3 domain competes with eIF4Gc for binding to eIF4A and surprisingly is sufficient to inhibit translation initiation. Mutations that abolish eIF4A binding negate both functions of the cMA3. Interestingly mutations in the Akt phosphorylation site influenced neither cMA3 binding to eIF4A nor its ability to inhibit translation initiation. Finally, our structural analysis reveals MA3 domains to be a novel subfamily of VHS domains.     

Radioimmunoassay for prednisolone

A radioimmunoassay method for the measurement of prednisolone and its 20β-OH metabolite in peripheral serum is presented. The method is capable of detecting 10.0 picograms of prednisolone in 0.1 mls of diluted serum or 1 nanogram in 0. 1 ml of undiluted serum. Hydrocortisone was the only endogenous steroid tested that cross-reacted significantly with the prednisolone antibody. The specificity of the primary antibody is strongly influenced by the double bond at the 1-position and the hydroxyl group at the 11-position on the steroid nucleus.Measurement of serum concentrations of prednisolone was accomplished in man and dog following oral dosages of Delta-Cortef^® (prednisolone) and Deltasone^® (prednisone). It was possible to use prednisolone as an index of the latter compound because of its rapid metabolic conversion to prednisolone.The number of serum samples which may be processed each day is limited only by the capacity of the liquid scintillation counter used. As many as 200 samples per day may easily be processed by one skilled technician. This capability, aside from the greater sensitivity, precision and accuracy offered by this method, provides a distinct advantage in the analysis of large numbers of samples which are required in bioavailability studies.     

Transport of long-chain fatty acids in Escherichia coli. Evidence for role of fadL gene product as long-chain fatty acid receptor

Transport of long-chain fatty acids (LCFA) across the cytoplasmic membrane of Escherichia coli requires functional fadL and fadD genes. The fadD gene codes for an acyl-CoA synthetase (fatty acid: CoA ligase (AMP forming] which has broad chain length specificity and is loosely bound to the cytoplasmic membrane. The fadL gene codes for a 43,000-dalton cytoplasmic membrane protein which, acting by an unknown mechanism, is needed specifically for LCFA transport. As a first step to define the role of the fadL gene product, studies were performed to determine if it functions as a LCFA receptor. The LCFA-binding activity was quantitated in intact cells in the absence of LCFA transport by comparing the binding of LCFA in fadD fadL and fadD fadL+ strains. These studies revealed that (i) fadD fadL+ strains bind 6-fold more LCFA than fadD fadL strains; (ii) fadD fadL strains harboring a plasmid containing the fadL gene bind 16-fold more LCFA than fadD fadL strains harboring only the plasmid vector; and (iii) the fadL-specific LCFA-binding activity is regulated by the fadR gene and catabolite repression. Studies with fadL strains harboring fadL plasmids containing in vitro constructed deletions indicate that mutations which alter the physical properties of the 43,000-dalton fadL gene product also affect fadL gene product-specific LCFA-binding activity. Overall, these studies suggest that one role of the fadL gene product in the LCFA transport process is to sequester LCFA at sites in the cell membrane for transport.     

A transforming activity not detected by DNA transfer to NIH 3T3 cells is detected by JB6 mouse epidermal cells.

Transfection of four different mouse epidermal tumor cell DNAs into NIH 3T3 cells yielded neither morphologically altered foci nor anchorage independence. However, promotion-sensitive, but not promotion-insensitive, JB6 mouse epidermal cell lines were permissive for the expression of anchorage independence after transfection of DNA from three of these tumor cell lines. This transforming activity and the promotion-sensitive activity that confers sensitivity to promotion of transformation show differences in restriction enzyme sensitivity. In view of this difference and the differences in both recipient cells and 12-O-tetradecanoyl-phorbol-13-acetate dependence of expression, it appears that the transforming activity and the promotion-sensitive activity are specified by different genes. The JB6 promotion-sensitive cell lines may be useful for detecting and cloning transforming genes that escape detection in the NIH 3T3 cell focus assay.     

Activation mechanism of rabbit skeletal muscle myosin light chain kinase. 5'-p-fluorosulfonylbenzoyl adenosine as a probe of the MgATP-binding site of the calmodulin-bound and calmodulin-free enzyme

5'-p-fluorosulfonylbenzoyl adenosine (FSBA), an ATP-like affinity labelling reagent, reacted with rabbit skeletal muscle myosin light chain kinase (skMLCK) and its calmodulin complex in a site-specific manner. Reaction was dependent upon the presence of the adenosine moiety of FSBA, saturated with increasing FSBA, was inhibited by MgATP, and was accompanied by stoichiometric incorporation of [14C]FSBA. The kinetic constants describing the reaction were similar for skMLCK and its calmodulin complex: k3 = -0.040 min-1 and -0.038 min-1, and Ki = 0.18 mM and 0.40 mM, respectively. It is concluded that the MgATP-binding site on skMLCK remains accessible at all times and maintains a near constant conformation.     

Influence of ionophores which bind calcium on the release of norepinephrine from synaptosomes.

A preparation of synaptosomes isolated from rat brain was used as a model of nerve to study affects of drugs on uptake and release of biogenic amines. The influence of ionophores, which bind calcium, on the release of noripinephrine from synaptosomes was examined to determine their effect on the release of the amine. A23187 induced release of norepinephrine mainly as the amine and this action was enhanced by calcium and depressed by magnetism. X-537A however, released norepinephrine mostly as deaminated metabolites but acted independently of calcium or magnetism. A23187, therefore is thought to be associated at least in part, with exocytotic amine release, possibly by enhancing entry of calcium across the plasma membrane. X-537A on the other hand may act as a carrier of the amine across the vesicular membrane and expose the amine to intrasynaptosomal monoamine oxidase.