Substrate translocation and inhibition in human dicarboxylate transporter NaDC3.

The human high-affinity sodium-dicarboxylate cotransporter (NaDC3) imports various substrates into the cell as tricarboxylate acid cycle intermediates, lipid biosynthesis precursors and signaling molecules. Understanding the cellular signaling process and developing inhibitors require knowledge of the structural basis of the dicarboxylate specificity and inhibition mechanism of NaDC3. To this end, we determined the cryo-electron microscopy structures of NaDC3 in various dimers, revealing the protomer in three conformations: outward-open C, outward-occluded C and inward-open C.

Racial, ethnic and neighborhood socioeconomic differences in incidence of dementia: A regional retrospective cohort study.

Background: Evidence on the effects of neighborhood socioeconomic disadvantage on dementia risk in racially and ethically diverse populations is limited. Our objective was to evaluate the relative extent to which neighborhood disadvantage accounts for racial/ethnic variation in dementia incidence rates. Secondarily, we evaluated the spatial relationship between neighborhood disadvantage and dementia risk.

Evaluating and Modeling Neighborhood Diversity and Health Using Electronic Health Records.

Background: Electronic health records (EHRs) provide researchers with abundant sample sizes, detailed clinical data, and other advantages for performing high-quality observational health research on diverse populations. We review and demonstrate strategies for the design and analysis of cohort studies on neighborhood diversity and health, including evaluation of the effects of race, ethnicity, and neighborhood socioeconomic position on disease prevalence and health outcomes, using localized EHR data.

Methods: Design strategies include integrating and harmonizing EHR data across multiple local health systems and defining the population(s) of interest and cohort extraction procedures for a given analysis based on the goal(s) of the study.

Biosynthesis of Largimycins in Involves Transient β-Alkylation and Cryptic Halogenation Steps Unprecedented in the Leinamycin Family.

Largimycins A1 and A2 are key members of a recently identified family of hybrid nonribosomal peptide polyketides belonging to the scarcely represented group of antitumor leinamycins. They are encoded by the gene cluster of . This cluster contains a halogenase gene and two sets of genes for the biosynthesis and incorporation of β branches at C3 and C9.

Lysosomal Storage and Albinism Due to Effects of a De Novo CLCN7 Variant on Lysosomal Acidification.

Optimal lysosome function requires maintenance of an acidic pH maintained by proton pumps in combination with a counterion transporter such as the Cl/H exchanger, CLCN7 (ClC-7), encoded by CLCN7. The role of ClC-7 in maintaining lysosomal pH has been controversial. In this paper, we performed clinical and genetic evaluations of two children of different ethnicities.

Uncovering production of specialized metabolites by Streptomyces argillaceus: Activation of cryptic biosynthesis gene clusters using nutritional and genetic approaches.

Sequencing of Streptomyces genomes has revealed they harbor a high number of biosynthesis gene cluster (BGC), which uncovered their enormous potentiality to encode specialized metabolites. However, these metabolites are not usually produced under standard laboratory conditions. In this manuscript we report the activation of BGCs for antimycins, carotenoids, germicidins and desferrioxamine compounds in Streptomyces argillaceus, and the identification of the encoded compounds.

Extended gamma-ray sources around pulsars constrain the origin of the positron flux at Earth.

The unexpectedly high flux of cosmic-ray positrons detected at Earth may originate from nearby astrophysical sources, dark matter, or unknown processes of cosmic-ray secondary production. We report the detection, using the High-Altitude Water Cherenkov Observatory (HAWC), of extended tera-electron volt gamma-ray emission coincident with the locations of two nearby middle-aged pulsars (Geminga and PSR B0656+14). The HAWC observations demonstrate that these pulsars are indeed local sources of accelerated leptons, but the measured tera-electron volt emission profile constrains the diffusion of particles away from these sources to be much slower than previously assumed.

Time-of-flight mass measurements for nuclear processes in neutron star crusts.

We present results from time-of-flight nuclear mass measurements at the National Superconducting Cyclotron Laboratory that are relevant for neutron star crust models. The masses of 16 neutron-rich nuclei in the scandium-nickel range were determined simultaneously, with the masses of (61)V, (63)Cr, (66)Mn, and (74)Ni measured for the first time with mass excesses of -30.510(890) MeV, -35.

Participation of NMDA-glutamatergic receptors in hippocampal neuronal damage caused by adult-onset hypothyroidism.

We analyzed the participation of N-methyl-d-aspartate (NMDA) receptors in the neuronal damage caused by adult-onset hypothyroidism. Wistar rats were randomly assigned into four groups. The euthyroid group received tap water.

Production and beta decay of rp-process nuclei 96Cd, 98In, and 100Sn.

The beta-decay properties of the N=Z nuclei 96Cd, 98In, and 100Sn have been studied. These nuclei were produced at the National Superconducting Cyclotron Laboratory by fragmenting a 120 MeV/nucleon 112Sn primary beam on a Be target. The resulting radioactive beam was filtered in the A1900 and the newly commissioned Radio Frequency Fragment Separator to achieve a purity level suitable for decay studies.

Z = 50 shell gap near 100Sn from intermediate-energy Coulomb excitations in even-mass 106-112Sn isotopes.

Rare isotope beams of neutron-deficient 106,108,110Sn from the fragmentation of 124Xe were employed in an intermediate-energy Coulomb excitation experiment. The measured B(E2,0(1)(+)-->2(1)(+)) values for 108Sn and 110Sn and the results obtained for the 106Sn show that the transition strengths for these nuclei are larger than predicted by current state-of-the-art shell-model calculations. This discrepancy might be explained by contributions of the protons from within the Z = 50 shell to the structure of low-energy excited states in this region.

Influence of high-calorie (cafeteria) diets on the population of Paneth cells in the small intestine of the rat.

A high-calorie (cafeteria) diet is known to cause changes in the intestinal morphology and functioning that seem to be related to calorie overfeeding. Among the cell lineages found in the small intestine epithelium, the Paneth cell (PC) population is known to be influenced by factors related mainly to the intestinal microbiota. The role of PCs in the intestinal cell concert remains unclear, because experimental evidence suggests PC involvement in local processes other than protection against pathogens.

Probing shell structure and shape changes in neutron-rich sulfur isotopes through transient-field g-factor measurements on fast radioactive beams of 38S and 40S.

The shell structure underlying shape changes in neutron-rich nuclei near N = 28 has been investigated by a novel application of the transient-field technique to measure the first-excited-state g factors in 38S and 40S produced as fast radioactive beams. There is a fine balance between proton and neutron contributions to the magnetic moments in both nuclei. The g factor of deformed 40S does not resemble that of a conventional collective nucleus because spin contributions are more important than usual.

Differential aromatase (CYP19) expression in human arteries from normal and neoplasic uterus: an immunohistochemical and in situ hybridization study.

Aromatase CYP19 catalyzes the synthesis of estrogen from androgens in a tissue-specific manner. This enzyme is present in several tissues, including gonads, brain and fatty tissue. More recently, its presence has been described in vessels.

Quadrupole deformation of the self-conjugate nucleus 72Kr.

We report on the first determination of the absolute B(E2;0+(1)-->2+(1)) excitation strength in the N=Z nucleus 72Kr. 72Kr is the heaviest N=Z nucleus for which this quantity has been measured and provides a benchmark in a region of the nuclear chart dominated by rapidly changing deformations and shapes mediated by the interplay of strongly oblate and prolate-driving orbitals. The deduced quadrupole deformation strength is in agreement with a variety of self-consistent models that predict an oblate shape for the ground state of 72Kr.

Transient expression of 5-HT1A receptor binding sites in some areas of the rat CNS during postnatal development.

The developmental evolution of 5-HT1A receptor binding sites was examined in the rat CNS during the early postnatal period using quantitative autoradiography and binding assays with 3H-8-OH-DPAT as the selective ligand. A progressive increase in the density of 5-HT1A sites was observed in the hippocampus, septum and cerebral cortex, up to adult levels which were reached around the third postnatal week. In contrast, complex biphasic (increase then decrease) changes were noted in other structures (for instance the nucleus of the lateral lemniscus), and even a progressive decrease in the density of 5-HT1A sites took place in the cerebellum during the first two postnatal weeks.