Leaky gut biomarkers in depression and suicidal behavior - Ohlsson L, Gustafsson A, Lavant E, Suneson K, Brundin L, Westrin A, Ljunggren L, Lindqvist D.
OBJECTIVE: Inflammation is associated with major depressive disorder (MDD) and suicidal behavior. According to the "leaky gut hypothesis", increased intestinal permeability may contribute to this relationship via bacterial translocation across enterocytes.... (Source: SafetyLit)
Source: SafetyLit - October 27, 2018 Category: International Medicine & Public Health Tags: Suicide and Self-Harm Source Type: news
Translocation of a Stray Cat Infected with Rabies from North Carolina to a Terrestrial Rabies-Free County in Ohio, 2017
On July 24, 2017, the Ohio Department of Health was notified of a positive rabies test result from a domestic cat in Summit County, a county considered free from terrestrial rabies. (Source: CDC Morbidity and Mortality Weekly Report)
Source: CDC Morbidity and Mortality Weekly Report - October 25, 2018 Category: American Health Tags: MMWR Morbidity & Mortality Weekly Report Outbreaks Rabies Rabies Vaccine Swine Influenza Variant Influenza Source Type: news
Sphingosine 1-phosphate stimulates eyelid closure in the developing rat by stimulating EGFR signaling
In many mammals, the eyelids migrate over the eye and fuse during embryogenesis to protect the cornea from damage during birth and early life. Loss-of-function mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway cause an eyes-open-at-birth (EOB) phenotype in rodents. We identified an insertional mutation in Spinster homolog 2 (Spns2) in a strain of transgenic rats exhibiting the EOB phenotype. Spns2, a sphingosine 1-phosphate (S1P) transporter that releases S1P from cells, was enriched at the tip of developing eyelids in wild-type rat embryos. Spns2 expression or treatment with S1P or any one ...
Source: Signal Transduction Knowledge Environment - October 23, 2018 Category: Science Authors: Bian, G., Yu, C., Liu, L., Fang, C., Chen, K., Ren, P., Zhang, Q., Liu, F., Zhang, K., Xue, Q., Xiang, J., Guo, H., Song, J., Zhao, Y., Wu, W., Chung, S. K., Sun, R., Ju, G., Wang, J. Tags: STKE Research Articles Source Type: news
Heredity matters: Ancestral protease functions as protein import motor in chloroplasts
(Osaka University) Japanese researchers identified a large novel protein complex in the inner chloroplast membrane that functions as a motor to import proteins into the chloroplast. Components of the complex evolved from a protein of the endosymbiont cyanobacterium-like ancestor of chloroplasts that lost its protein-degrading function but retained its motor ability. These findings solve a longstanding mystery surrounding this protein translocation system that uniquely evolved in photosynthetic eukaryotes. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - October 22, 2018 Category: Biology Source Type: news
Structure and dynamics of the yeast SWR1-nucleosome complex
The yeast SWR1 complex exchanges histone H2A in nucleosomes with Htz1 (H2A.Z in humans). The cryo–electron microscopy structure of the SWR1 complex bound to a nucleosome at 3.6-angstrom resolution reveals details of the intricate interactions between components of the SWR1 complex and its nucleosome substrate. Interactions between the Swr1 motor domains and the DNA wrap at superhelical location 2 distort the DNA, causing a bulge with concomitant translocation of the DNA by one base pair, coupled to conformational changes of the histone core. Furthermore, partial unwrapping of the DNA from the histone core takes place...
Source: ScienceNOW - October 11, 2018 Category: Science Authors: Willhoft, O., Ghoneim, M., Lin, C.-L., Chua, E. Y. D., Wilkinson, M., Chaban, Y., Ayala, R., McCormack, E. A., Ocloo, L., Rueda, D. S., Wigley, D. B. Tags: Biochemistry, Online Only r-articles Source Type: news
Systemic control of legume susceptibility to rhizobial infection by a mobile microRNA
Nitrogen-fixing root nodules on legumes result from two developmental processes, bacterial infection and nodule organogenesis. To balance symbiosis and plant growth, legume hosts restrict nodule numbers through an inducible autoregulatory process. Here, we present a mechanism where repression of a negative regulator ensures symbiotic susceptibility of uninfected roots of the host Lotus japonicus. We show that microRNA miR2111 undergoes shoot-to-root translocation to control rhizobial infection through posttranscriptional regulation of the symbiosis suppressor TOO MUCH LOVE in roots. miR2111 maintains a susceptible default ...
Source: ScienceNOW - October 11, 2018 Category: Science Authors: Tsikou, D., Yan, Z., Holt, D. B., Abel, N. B., Reid, D. E., Madsen, L. H., Bhasin, H., Sexauer, M., Stougaard, J., Markmann, K. Tags: Botany, Cell Biology reports Source Type: news
Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations
G protein–coupled receptors (GPCRs) are the largest class of cell surface signaling proteins, participate in nearly all physiological processes, and are the targets of 30% of marketed drugs. Typically, nanomolar to micromolar concentrations of ligand are used to activate GPCRs in experimental systems. We detected GPCR responses to a wide range of ligand concentrations, from attomolar to millimolar, by measuring GPCR-stimulated production of cyclic adenosine monophosphate (cAMP) with high spatial and temporal resolution. Mathematical modeling showed that femtomolar concentrations of ligand activated, on average, 40% o...
Source: Signal Transduction Knowledge Environment - October 9, 2018 Category: Science Authors: Civciristov, S., Ellisdon, A. M., Suderman, R., Pon, C. K., Evans, B. A., Kleifeld, O., Charlton, S. J., Hlavacek, W. S., Canals, M., Halls, M. L. Tags: STKE Research Articles Source Type: news
CDK12-mediated transcriptional regulation of noncanonical NF-{kappa}B components is essential for signaling
Members of the family of nuclear factor B (NF-B) transcription factors are critical for multiple cellular processes, including regulating innate and adaptive immune responses, cell proliferation, and cell survival. Canonical NF-B complexes are retained in the cytoplasm by the inhibitory protein IBα, whereas noncanonical NF-B complexes are retained by p100. Although activation of canonical NF-B signaling through the IBα kinase complex is well studied, few regulators of the NF-B–inducing kinase (NIK)–dependent processing of noncanonical p100 to p52 and the subsequent nuclear translocation of p52 have ...
Source: Signal Transduction Knowledge Environment - July 31, 2018 Category: Science Authors: Henry, K. L., Kellner, D., Bajrami, B., Anderson, J. E., Beyna, M., Bhisetti, G., Cameron, T., Capacci, A. G., Bertolotti-Ciarlet, A., Feng, J., Gao, B., Hopkins, B., Jenkins, T., Li, K., May-Dracka, T., Murugan, P., Wei, R., Zeng, W., Allaire, N., Buckle Tags: STKE Research Articles Source Type: news
Regulation of thymocyte trafficking by Tagap, a GAP domain protein linked to human autoimmunity
Multiple autoimmune pathologies are associated with single-nucleotide polymorphisms of the human gene TAGAP, which encodes TAGAP, a guanosine triphosphatase (GTPase)–activating protein. We showed in mice that Tagap-mediated signaling by the sema3E/plexin-D1 ligand-receptor complex attenuates thymocytes’ adhesion to the cortex through their β1-containing integrins. By promoting thymocyte detachment within the cortex of the thymus, Tagap-mediated signaling enabled their translocation to the medulla, which is required for continued thymic selection. Tagap physically interacted with the cytoplasmic domain of p...
Source: Signal Transduction Knowledge Environment - June 12, 2018 Category: Science Authors: Duke-Cohan, J. S., Ishikawa, Y., Yoshizawa, A., Choi, Y.-I., Lee, C.-N., Acuto, O., Kissler, S., Reinherz, E. L. Tags: STKE Research Articles Source Type: news
High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane
Mitochondrial adenosine triphosphate (ATP) synthase comprises a membrane embedded Fo motor that rotates to drive ATP synthesis in the F1 subunit. We used single-particle cryo–electron microscopy (cryo-EM) to obtain structures of the full complex in a lipid bilayer in the absence or presence of the inhibitor oligomycin at 3.6- and 3.8-angstrom resolution, respectively. To limit conformational heterogeneity, we locked the rotor in a single conformation by fusing the F6 subunit of the stator with the subunit of the rotor. Assembly of the enzyme with the F6- fusion caused a twisting of the rotor and a 9° rotation of ...
Source: ScienceNOW - May 10, 2018 Category: Science Authors: Srivastava, A. P., Luo, M., Zhou, W., Symersky, J., Bai, D., Chambers, M. G., Faraldo-Gomez, J. D., Liao, M., Mueller, D. M. Tags: Biochemistry, Online Only r-articles Source Type: news
Erratum for the Report "Translocation of a gut pathobiont drives autoimmunity in mice and humans" by S. Manfredo Vieira, M. Hiltensperger, V. Kumar, D. Zegarra-Ruiz, C. Dehner, N. Khan, F. R. C. Costa, E. Tiniakou, T. Greiling, W. Ruff, A. Barbieri, C. Kriegel, S. S. Mehta, J. R. Knight, D. Jain, A. L. Goodman, M. A. Kriegel
(Source: ScienceNOW)
Source: ScienceNOW - May 3, 2018 Category: Science Tags: Errata Source Type: news
First steps of translocation elucidated
(Source: ScienceNOW)
Source: ScienceNOW - April 19, 2018 Category: Science Authors: Hurtley, S. M. Tags: Molecular Biology twis Source Type: news
The nuclear translocation of the kinases p38 and JNK promotes inflammation-induced cancer
The stimulated nuclear translocation of signaling proteins, such as MAPKs, is a necessity for the initiation and regulation of their physiological functions. Previously, we determined that nuclear translocation of the MAPKs p38 and JNK involves binding to heterodimers comprising importin 3 and either importin 7 or importin 9. Here, we identified the importin-binding region in p38 and JNK and developed a myristoylated peptide targeting this site that we called PERY. The PERY peptide specifically blocked the interaction of p38 and JNK with the importins, restricted their nuclear translocation, and inhibited phosphorylation o...
Source: Signal Transduction Knowledge Environment - April 10, 2018 Category: Science Authors: Maik-Rachline, G., Zehorai, E., Hanoch, T., Blenis, J., Seger, R. Tags: STKE Research Articles Source Type: news
Translocation of a gut pathobiont drives autoimmunity in mice and humans
Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells. Hepatocyte–E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice indu...
Source: ScienceNOW - March 8, 2018 Category: Science Authors: Manfredo Vieira, S., Hiltensperger, M., Kumar, V., Zegarra-Ruiz, D., Dehner, C., Khan, N., Costa, F. R. C., Tiniakou, E., Greiling, T., Ruff, W., Barbieri, A., Kriegel, C., Mehta, S. S., Knight, J. R., Jain, D., Goodman, A. L., Kriegel, M. A. Tags: Immunology, Medicine, Diseases reports Source Type: news
Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation
The multidrug transporter permeability (P)–glycoprotein is an adenosine triphosphate (ATP)–binding cassette exporter responsible for clinical resistance to chemotherapy. P-glycoprotein extrudes toxic molecules and drugs from cells through ATP-powered conformational changes. Despite decades of effort, only the structures of the inward-facing conformation of P-glycoprotein are available. Here we present the structure of human P-glycoprotein in the outward-facing conformation, determined by cryo–electron microscopy at 3.4-angstrom resolution. The two nucleotide-binding domains form a closed dimer occluding t...
Source: ScienceNOW - February 22, 2018 Category: Science Authors: Kim, Y., Chen, J. Tags: Biochemistry, Medicine, Diseases reports Source Type: news
