INTS6 (integrator complex subunit 6)

Review on INTS6 (integrator complex subunit 6), with data on DNA, on the protein encoded, and where the gene is implicated

Feed the Future Mali Livestock Technology Scaling Program (FtF-MLTSP) - Participatory assessment of animal health service delivery systems in Mali: Constraints and opportunities

United States Agency for International Developmen

A refined Razumov-Stroganov conjecture

We extend the Razumov-Stroganov conjecture relating the groundstate of the O(1) spin chain to alternating sign matrices, by relating the groundstate of the monodromy matrix of the O(1) model to the so-called refined alternating sign matrices, i.e. with prescribed configuration of their first row, as well as to refined fully-packed loop configurations on a square grid, keeping track both of the loop connectivity and of the configuration of their top row. We also conjecture a direct relation between this groundstate and refined totally symmetric self-complementary plane partitions, namely, in their formulation as sets of non-intersecting lattice paths, with prescribed last steps of all paths.Comment: 20 pages, 4 figures, uses epsf and harvmac macros a few typos correcte

Measurement of the reaction \gamma p \TO K^ + \Lambda(1520) at photon energies up to 2.65 GeV

The reaction \gamma p \TO K^+\Lambda(1520) was measured in the energy range from threshold to 2.65 GeV with the SAPHIR detector at the electron stretcher facility ELSA in Bonn. The $\Lambda(1520)$ production cross section was analyzed in the decay modes $pK^-$, $n \bar{K}^0$, $\Sigma^{\pm}\pi^{\mp}$, and $\Lambda\pi^+\pi^-$ as a function of the photon energy and the squared four-momentum transfer $t$. While the cross sections for the inclusive reactions rise steadily with energy, the cross section of the process \gamma p \TO K^+\Lambda(1520) peaks at a photon energy of about 2.0 GeV, falls off exponentially with $t$, and shows a slope flattening with increasing photon energy. The angular distributions in the $t$-channel helicity system indicate neither a $K$ nor a $K^\star$ exchange dominance. The interpretation of the $\Lambda(1520)$ as a $\Sigma(1385)\pi$ molecule is not supported.Comment: 11 pages, 16 figures, 4 table

Feed the Future Mali: Scaling up technological and institutional livestock innovations

United States Agency for International Developmen

The impact of CFNS-causing EFNB1 mutations on ephrin-B1 function

BACKGROUND: Mutations of EFNB1 cause the X-linked malformation syndrome craniofrontonasal syndrome (CFNS). CFNS is characterized by an unusual phenotypic pattern of inheritance, because it affects heterozygous females more severely than hemizygous males. This sex-dependent inheritance has been explained by random X-inactivation in heterozygous females and the consequences of cellular interference of wild type and mutant EFNB1-expressing cell populations. EFNB1 encodes the transmembrane protein ephrin-B1, that forms bi-directional signalling complexes with Eph receptor tyrosine kinases expressed on complementary cells. Here, we studied the effects of patient-derived EFNB1 mutations predicted to give rise to truncated ephrin-B1 protein or to disturb Eph/ephrin-B1 reverse ephrin-B1 signalling. Five mutations are investigated in this work: nonsense mutation c.196C > T/p.R66X, frameshift mutation c.614_615delCT, splice-site mutation c.406 + 2T > C and two missense mutations p.P54L and p.T111I. Both missense mutations are located in the extracellular ephrin domain involved in Eph-ephrin-B1 recognition and higher order complex formation. METHODS: Nonsense mutation c.196C > T/p.R66X, frameshift mutation c.614_615delCT and splice-site mutation c.406+2T > C were detected in the primary patient fibroblasts by direct sequencing of the DNA and were further analysed by RT-PCR and Western blot analyses.The impact of missense mutations p.P54L and p.T111I on cell behaviour and reverse ephrin-B1 cell signalling was analysed in a cell culture model using NIH 3T3 fibroblasts. These cells were transfected with the constructs generated by in vitro site-directed mutagenesis. Investigation of missense mutations was performed using the Western blot analysis and time-lapse microscopy. RESULTS AND DISCUSSION: Nonsense mutation c.196C > T/p.R66X and frameshift mutation c.614_615delCT escape nonsense-mediated RNA decay (NMD), splice-site mutation c.406+2T > C results in either retention of intron 2 or activation of a cryptic splice site in exon 2. However, c.614_615delCT and c.406+2T > C mutations were found to be not compatible with production of a soluble ephrin-B1 protein. Protein expression of the p.R66X mutation was predicted unlikely but has not been investigated.Ectopic expression of p.P54L ephrin-B1 resists Eph-receptor mediated cell cluster formation in tissue culture and intracellular ephrin-B1 Tyr324 and Tyr329 phosphorylation. Cells expressing p.T111I protein show similar responses as wild type expressing cells, however, phosphorylation of Tyr324 and Tyr329 is reduced. CONCLUSIONS: Pathogenic mechanisms in CFNS manifestation include impaired ephrin-B1 signalling combined with cellular interference

Nucleoside diphosphate kinase B is required for the formation of heterotrimeric G protein containing caveolae.

Caveolae are flask-shaped invaginations in the plasma membrane that serve to compartmentalize and organize signal transduction processes, including signals mediated by G protein-coupled receptors and heterotrimeric G proteins. Herein we report evidence for a close association of the nucleoside diphosphate kinase B (NDPK B) and caveolin proteins which is required for G protein scaffolding and caveolae formation. A concomitant loss of the proteins NDPK B, caveolin isoforms 1 (Cav1) and 3, and heterotrimeric G proteins occurred when one of these proteins was specifically depleted in zebrafish embryos. Co-immunoprecipitation of Cav1 with the G protein Gβ-subunit and NDPK B from zebrafish lysates corroborated the direct association of these proteins. Similarly, in embryonic fibroblasts from the respective knockout (KO) mice, the membrane content of the Cav1, Gβ, and NDPK B was found to be mutually dependent on one another. A redistribution of Cav1 and Gβ from the caveolae containing fractions of lower density to other membrane compartments with higher density could be detected by means of density gradient fractionation of membranes derived from NDPK A/B KO mouse embryonic fibroblasts (MEFs) and after shRNA-mediated NDPK B knockdown in H10 cardiomyocytes. This redistribution could be visualized by confocal microscopy analysis showing a decrease in the plasma membrane bound Cav1 in NDPK A/B KO cells and vice versa and a decrease in the plasma membrane pool of NDPK B in Cav1 KO cells. Consequently, ultrastructural analysis revealed a reduction of surface caveolae in the NDPK A/B KO cells. To prove that the disturbed subcellular localization of Cav1 in NDPK A/B KO MEFs as well as NDPK B in Cav1 KO MEFs is a result of the loss of NDPK B and Cav1, respectively, we performed rescue experiments. The adenoviral re-expression of NDPK B in NDPK A/B KO MEFs rescued the protein content and the plasma membrane localization of Cav1. The expression of an EGFP-Cav1 fusion protein in Cav1-KO cells induced a restoration of NDPK B expression levels and its appearance at the plasma membrane. We conclude from these findings that NDPK B, heterotrimeric G proteins, and caveolins are mutually dependent on each other for stabile localization and caveolae formation at the plasma membrane. The data point to a disturbed transport of caveolin/G protein/NDPK B complexes from intracellular membrane compartments if one of the components is missing

Population-Based Survey of Complementary and Alternative Medicine Usage, Patient Satisfaction, and Physician Involvement

Background. With an increasing proportion of Americans using complementary or alternative medicine (CAM), physicians need to know which patients are using CAM to effectively manage care. Methods. In this cross-sectional study, telephone interviews were conducted with 1,584 South Carolina adults (ages 18 and older); 66% responded to the survey of demographics, general health, frequency of CAM use, perceived CAM effectiveness, and physician knowledge of CAM use. Results. A total of 44% had used a CAM during the past year. Increasing age and higher education were significantly associated with CAM use. More than 60% perceived CAM therapy as very effective, and 89% said they would recommend CAM to others. Physicians were unaware of CAM use in 57% of their patients using CAM. Conclusion. Complementary or alternative medicine use in this rural Southern state is similar to national usage. Users view CAM as effective. Physicians are frequently unaware of patients\u27 CAM use. More research is needed to establish CAM effectiveness and how CAM affects medical care, training, and public health

Molecular architecture of Gαo and the structural basis for RGS16-mediated deactivation

Heterotrimeric G proteins relay extracellular cues from heptahelical transmembrane receptors to downstream effector molecules. Composed of an α subunit with intrinsic GTPase activity and a βγ heterodimer, the trimeric complex dissociates upon receptor-mediated nucleotide exchange on the α subunit, enabling each component to engage downstream effector targets for either activation or inhibition as dictated in a particular pathway. To mitigate excessive effector engagement and concomitant signal transmission, the Gα subunit's intrinsic activation timer (the rate of GTP hydrolysis) is regulated spatially and temporally by a class of GTPase accelerating proteins (GAPs) known as the regulator of G protein signaling (RGS) family. The array of G protein-coupled receptors, Gα subunits, RGS proteins and downstream effectors in mammalian systems is vast. Understanding the molecular determinants of specificity is critical for a comprehensive mapping of the G protein system. Here, we present the 2.9 Å crystal structure of the enigmatic, neuronal G protein Gαo in the GTP hydrolytic transition state, complexed with RGS16. Comparison with the 1.89 Å structure of apo-RGS16, also presented here, reveals plasticity upon Gαo binding, the determinants for GAP activity, and the structurally unique features of Gαo that likely distinguish it physiologically from other members of the larger Gαi family, affording insight to receptor, GAP and effector specificity

Studying the Key Intermediate of RNA Autohydrolysis by Cryogenic Gas-Phase Infrared Spectroscopy

Over the course of the COVID-19 pandemic, mRNA-based vaccines have gained tremendous importance. The development and analysis of modified RNA molecules benefit from advanced mass spectrometry and require sufficient understanding of fragmentation processes. Analogous to the degradation of RNA in solution by autohydrolysis, backbone cleavage of RNA strands was equally observed in the gas phase; however, the fragmentation mechanism remained elusive. In this work, autohydrolysis-like intermediates were generated from isolated RNA dinucleotides in the gas phase and investigated using cryogenic infrared spectroscopy in helium nanodroplets. Data from both experiment and density functional theory provide evidence for the formation of a five-membered cyclic phosphate intermediate and rule out linear or six-membered structures. Furthermore, the experiments show that another prominent condensed-phase reaction of RNA nucleotides can be induced in the gas phase: the tautomerization of cytosine. Both observed reactions are therefore highly universal and intrinsic properties of the investigated molecules