Translocation of bighorn sheep in Arizona has positive genetic outcomes
(University of Wyoming) Research shows it is possible to re-establish bighorn sheep populations without a reduction of genetic diversity over a short period and without erosion of ancestral lineage. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - March 6, 2019 Category: International Medicine & Public Health Source Type: news

Immunometabolism regulates TCR recycling and iNKT cell functions
Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that express an invariant T cell receptor (TCR), which recognizes glycolipid antigens presented on CD1d molecules. These cells are phenotypically and functionally distinct from conventional T cells. When we characterized the metabolic activity of iNKT cells, consistent with their activated phenotype, we found that they had much less mitochondrial respiratory capacity but increased glycolytic activity in comparison to naïve conventional CD4+ T cells. After TCR engagement, iNKT cells further increased aerobic glycolysis, which was important for the expre...
Source: Signal Transduction Knowledge Environment - February 26, 2019 Category: Science Authors: Fu, S., Zhu, S., Tian, C., Bai, S., Zhang, J., Zhan, C., Xie, D., Wang, L., Li, Z., Li, J., Zhang, H., Zhou, R., Tian, Z., Xu, T., Bai, L. Tags: STKE Research Articles Source Type: news

Structure of the posttranslational Sec protein-translocation channel complex from yeast
The Sec61 protein-conducting channel mediates transport of many proteins, such as secretory proteins, across the endoplasmic reticulum (ER) membrane during or after translation. Posttranslational transport is enabled by two additional membrane proteins associated with the channel, Sec63 and Sec62, but its mechanism is poorly understood. We determined a structure of the Sec complex (Sec61-Sec63-Sec71-Sec72) from Saccharomyces cerevisiae by cryo–electron microscopy (cryo-EM). The structure shows that Sec63 tightly associates with Sec61 through interactions in cytosolic, transmembrane, and ER-luminal domains, prying ope...
Source: ScienceNOW - January 3, 2019 Category: Science Authors: Itskanov, S., Park, E. Tags: Biochemistry reports Source Type: news

Restricting mitochondrial GRK2 post-ischemia confers cardioprotection by reducing myocyte death and maintaining glucose oxidation
Increased abundance of GRK2 [G protein–coupled receptor (GPCR) kinase 2] is associated with poor cardiac function in heart failure patients. In animal models, GRK2 contributes to the pathogenesis of heart failure after ischemia-reperfusion (IR) injury. In addition to its role in down-regulating activated GPCRs, GRK2 also localizes to mitochondria both basally and post-IR injury, where it regulates cellular metabolism. We previously showed that phosphorylation of GRK2 at Ser670 is essential for the translocation of GRK2 to the mitochondria of cardiomyocytes post-IR injury in vitro and that this localization promotes c...
Source: Signal Transduction Knowledge Environment - December 11, 2018 Category: Science Authors: Sato, P. Y., Chuprun, J. K., Grisanti, L. A., Woodall, M. C., Brown, B. R., Roy, R., Traynham, C. J., Ibetti, J., Lucchese, A. M., Yuan, A., Drosatos, K., Tilley, D. G., Gao, E., Koch, W. J. Tags: STKE Research Articles Source Type: news

The {beta}4 subunit of Cav1.2 channels is required for an optimal interferon response in cardiac muscle cells
The auxiliary β4 subunit of the cardiac Cav1.2 channel plays a poorly understood role in gene transcription. Here, we characterized the regulatory effects of the β4 subunit in H9c2 rat cardiac cells on the abundances of Ifnb mRNA [which encodes interferon-β (IFN-β)] and of the IFN-β–related genes Ddx58, Ifitm3, Irf7, Stat2, Ifih1, and Mx1, as well as on the abundances of the antiviral proteins DDX58, IRF7, STAT2, and IFITM3. Knocking down the β4 subunit in H9c2 cells reduced the expression of IFN-β–stimulated genes. In response to inhibition of the kinase JAK1, the abundances ...
Source: Signal Transduction Knowledge Environment - December 11, 2018 Category: Science Authors: Tammineni, E. R., Carrillo, E. D., Soto-Acosta, R., Angel-Ambrocio, A. H., Garcia, M. C., Bautista-Carbajal, P., del Angel, R. M., Sanchez, J. A. Tags: STKE Research Articles Source Type: news

Substrate-engaged 26S proteasome structures reveal mechanisms for ATP-hydrolysis-driven translocation
The 26S proteasome is the primary eukaryotic degradation machine and thus is critically involved in numerous cellular processes. The heterohexameric adenosine triphosphatase (ATPase) motor of the proteasome unfolds and translocates targeted protein substrates into the open gate of a proteolytic core while a proteasomal deubiquitinase concomitantly removes substrate-attached ubiquitin chains. However, the mechanisms by which ATP hydrolysis drives the conformational changes responsible for these processes have remained elusive. Here we present the cryo–electron microscopy structures of four distinct conformational stat...
Source: ScienceNOW - November 29, 2018 Category: Science Authors: de la Pena, A. H., Goodall, E. A., Gates, S. N., Lander, G. C., Martin, A. Tags: Biochemistry, Online Only r-articles Source Type: news

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

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

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

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

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

Defining the physiological role of SRP in protein-targeting efficiency and specificity
The signal recognition particle (SRP) enables cotranslational delivery of proteins for translocation into the endoplasmic reticulum (ER), but its full in vivo role remains incompletely explored. We combined rapid auxin-induced SRP degradation with proximity-specific ribosome profiling to define SRP’s in vivo function in yeast. Despite the classic view that SRP recognizes amino-terminal signal sequences, we show that SRP was generally essential for targeting transmembrane domains regardless of their position relative to the amino terminus. By contrast, many proteins containing cleavable amino-terminal signal peptides ...
Source: ScienceNOW - February 8, 2018 Category: Science Authors: Costa, E. A., Subramanian, K., Nunnari, J., Weissman, J. S. Tags: Cell Biology reports Source Type: news

Factors affecting the success of grizzly bear translocations
(Wiley) The number of grizzly bear translocations has increased in recent years to protect the bears and reduce conflicts with humans. In a recent Journal of Wildlife Management analysis of translocations in Alberta, Canada, researchers found that the most important factors for translocation success were the level of human-caused mortality risk at the release site and the time of year when the translocation occurred. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - January 10, 2018 Category: Biology Source Type: news

Increased systemic microbial translocation is associated with depression during early pregnancy - Zhou Z, Guille C, Ogunrinde E, Liu R, Luo Z, Powell A, Jiang W.
Plasma level of microbial translocation is a marker of mucosal permeability. Increased mucosal permeability ignites elevated microbial translocation and as a consequence of systemic inflammation. Pregnant women with depression have higher levels of inflamm... (Source: SafetyLit)
Source: SafetyLit - December 1, 2017 Category: International Medicine & Public Health Tags: Ergonomics, Human Factors, Anthropometrics, Physiology Source Type: news

Nuclear hyaluronidase 2 drives alternative splicing of CD44 pre-mRNA to determine profibrotic or antifibrotic cell phenotype
The cell surface protein CD44 is involved in diverse physiological processes, and its aberrant function is linked to various pathologies such as cancer, immune dysregulation, and fibrosis. The diversity of CD44 biological activity is partly conferred by the generation of distinct CD44 isoforms through alternative splicing. We identified an unexpected function for the ubiquitous hyaluronan-degrading enzyme, hyaluronidase 2 (HYAL2), as a regulator of CD44 splicing. Standard CD44 is associated with fibrotic disease, and its production is promoted through serine-arginine–rich (SR) protein–mediated exon exclusion. H...
Source: Signal Transduction Knowledge Environment - November 21, 2017 Category: Science Authors: Midgley, A. C., Oltean, S., Hascall, V., Woods, E. L., Steadman, R., Phillips, A. O., Meran, S. Tags: STKE Research Articles Source Type: news

Atomic model for the dimeric FO region of mitochondrial ATP synthase
Mitochondrial adenosine triphosphate (ATP) synthase produces the majority of ATP in eukaryotic cells, and its dimerization is necessary to create the inner membrane folds, or cristae, characteristic of mitochondria. Proton translocation through the membrane-embedded FO region turns the rotor that drives ATP synthesis in the soluble F1 region. Although crystal structures of the F1 region have illustrated how this rotation leads to ATP synthesis, understanding how proton translocation produces the rotation has been impeded by the lack of an experimental atomic model for the FO region. Using cryo–electron microscopy, we...
Source: ScienceNOW - November 16, 2017 Category: Science Authors: Guo, H., Bueler, S. A., Rubinstein, J. L. Tags: Biochemistry reports Source Type: news

Structure of the mitochondrial inner membrane AAA+ protease YME1 gives insight into substrate processing
We present an atomic model of a substrate-bound inner mitochondrial membrane AAA+ quality control protease in yeast, YME1. Our ~3.4-angstrom cryo–electron microscopy structure reveals how the adenosine triphosphatases (ATPases) form a closed spiral staircase encircling an unfolded substrate, directing it toward the flat, symmetric protease ring. Three coexisting nucleotide states allosterically induce distinct positioning of tyrosines in the central channel, resulting in substrate engagement and translocation to the negatively charged proteolytic chamber. This tight coordination by a network of conserved residues def...
Source: ScienceNOW - November 2, 2017 Category: Science Authors: Puchades, C., Rampello, A. J., Shin, M., Giuliano, C. J., Wiseman, R. L., Glynn, S. E., Lander, G. C. Tags: Online Only r-articles Source Type: news

The condensin complex is a mechanochemical motor that translocates along DNA
Condensin plays crucial roles in chromosome organization and compaction, but the mechanistic basis for its functions remains obscure. We used single-molecule imaging to demonstrate that Saccharomyces cerevisiae condensin is a molecular motor capable of adenosine triphosphate hydrolysis–dependent translocation along double-stranded DNA. Condensin’s translocation activity is rapid and highly processive, with individual complexes traveling an average distance of ≥10 kilobases at a velocity of ~60 base pairs per second. Our results suggest that condensin may take steps comparable in length to its ~50-nanometer c...
Source: ScienceNOW - November 2, 2017 Category: Science Authors: Terakawa, T., Bisht, S., Eeftens, J. M., Dekker, C., Haering, C. H., Greene, E. C. Tags: Biochemistry, Molecular Biology reports Source Type: news

Two classes of GGAA-microsatellites in a Ewing sarcoma context
(Nationwide Children's Hospital) In a study published in PLOS ONE, researchers describe two types of GGAA-microsatellites and their roles in EWS/FLI binding and gene regulation in Ewing sarcoma. Ewing sarcoma is the second most common pediatric bone malignancy. It is initiated by chromosomal translocation t(11;22)(q24;q12), which creates the fusion protein and oncogenic driver EWS/FLI. (Source: EurekAlert! - Cancer)
Source: EurekAlert! - Cancer - November 1, 2017 Category: Cancer & Oncology Source Type: news

University of Seville researchers reveal the role of a DNA repair mechanism
(University of Seville) An important step forward in understanding more exactly what the mechanisms are that allow, if not correctly repaired, certain DNA breaks to be exchanged with others, so generating chromosomal translocation. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - October 31, 2017 Category: International Medicine & Public Health Source Type: news

Inhibition of the oncogenic fusion protein EWS-FLI1 causes G2-M cell cycle arrest and enhanced vincristine sensitivity in Ewings sarcoma
Ewing’s sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is implicated in driving most ES cases by modulation of transcription and alternative splicing. The small-molecule YK-4-279 inhibits EWS-FLI1 function and induces apoptosis in ES cells. We aimed to identify both the underlying mechanism of the drug and potential combination therapies that might enhance its...
Source: Signal Transduction Knowledge Environment - October 3, 2017 Category: Science Authors: Zöllner, S. K., Selvanathan, S. P., Graham, G. T., Commins, R. M. T., Hong, S. H., Moseley, E., Parks, S., Haladyna, J. N., Erkizan, H. V., Dirksen, U., Hogarty, M. D., Üren, A., Toretsky, J. A. Tags: STKE Research Articles Source Type: news

Translocation Renal Cell Carcinoma: An Update
Microphthalmia-associated transcription (MiT) family translocation renal cell carcinoma (tRCC) comprises Xp11 tRCC and t(6;11) RCC.08/29/2017 (Source: Kidney Cancer Association)
Source: Kidney Cancer Association - August 29, 2017 Category: Urology & Nephrology Source Type: news

Scientists map sex chromosome evolution in pathogenic fungi
(Duke University) Duke researchers recently mapped the evolutionary turning point that transformed the pathogenic Cryptococcus fungus from an organism with thousands of sexes to only two. They found that during evolution, a reshuffling of DNA known as translocation brought together separate chunks of sex-determining genes onto a single chromosome, essentially mimicking the human X or Y chromosome. Surprisingly, these translocations occurred at the chromosome's centromeres, regions so dense that they were once thought to suppress recombination. (Source: EurekAlert! - Infectious and Emerging Diseases)
Source: EurekAlert! - Infectious and Emerging Diseases - August 11, 2017 Category: Infectious Diseases Source Type: news

Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104
Hsp100 polypeptide translocases are conserved members of the AAA+ family (adenosine triphosphatases associated with diverse cellular activities) that maintain proteostasis by unfolding aberrant and toxic proteins for refolding or proteolytic degradation. The Hsp104 disaggregase from Saccharomyces cerevisiae solubilizes stress-induced amorphous aggregates and amyloids. The structural basis for substrate recognition and translocation is unknown. Using a model substrate (casein), we report cryo–electron microscopy structures at near-atomic resolution of Hsp104 in different translocation states. Substrate interactions ar...
Source: ScienceNOW - July 20, 2017 Category: Science Authors: Gates, S. N., Yokom, A. L., Lin, J., Jackrel, M. E., Rizo, A. N., Kendsersky, N. M., Buell, C. E., Sweeny, E. A., Mack, K. L., Chuang, E., Torrente, M. P., Su, M., Shorter, J., Southworth, D. R. Tags: Biochemistry r-articles Source Type: news

Bidirectional eukaryotic DNA replication is established by quasi-symmetrical helicase loading
Bidirectional replication from eukaryotic DNA replication origins requires the loading of two ring-shaped minichromosome maintenance (MCM) helicases around DNA in opposite orientations. MCM loading is orchestrated by binding of the origin recognition complex (ORC) to DNA, but how ORC coordinates symmetrical MCM loading is unclear. We used natural budding yeast DNA replication origins and synthetic DNA sequences to show that efficient MCM loading requires binding of two ORC molecules to two ORC binding sites. The relative orientation of these sites, but not the distance between them, was found to be critical for MCM loading...
Source: ScienceNOW - July 20, 2017 Category: Science Authors: Coster, G., Diffley, J. F. X. Tags: Biochemistry, Molecular Biology reports Source Type: news

'Overturning established fact' leads to new new target in MLL-rearranged leukemia
(University of Colorado Anschutz Medical Campus) A University of Colorado Cancer Center paper published today in the journal Cancer Cell challenges existing understanding of potential therapeutic targets in MLL-translocation leukemia. Specifically, the study shows that within the family of MLL-related proteins, MLL2 and not MLL is the most appropriate target for drugs challenging the disease. In other words, drug developers aiming at MLL may have been missing slightly to one side of the real target. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - June 13, 2017 Category: International Medicine & Public Health Source Type: news

Cytogenetic Abnormalities Do Not Affect Prognosis in Pediatric CML
Chromosomal abnormalities such as a variant t(9;22) translocation do not appear to have significant prognostic impact on children with chronic myeloid leukemia. (Source: CancerNetwork)
Source: CancerNetwork - May 22, 2017 Category: Cancer & Oncology Authors: Dave Levitan Tags: Chronic Myeloid Leukemia Hematologic Malignancies News Source Type: news

Tetraspanin microdomains control localized protein kinase C signaling in B cells
Activation of B cells by the binding of antigens to the B cell receptor (BCR) requires the protein kinase C (PKC) family member PKCβ. Because PKCs must translocate to the plasma membrane to become activated, we investigated the mechanisms regulating their spatial distribution in mouse and human B cells. Through live-cell imaging, we showed that BCR-stimulated production of the second messenger diacylglycerol (DAG) resulted in the translocation of PKCβ from the cytosol to plasma membrane regions containing the tetraspanin protein CD53. CD53 was specifically enriched at sites of BCR signaling, suggesting that BCR-d...
Source: Signal Transduction Knowledge Environment - May 9, 2017 Category: Science Authors: Zuidscherwoude, M., Dunlock, V.-M. E., van den Bogaart, G., van Deventer, S. J., van der Schaaf, A., van Oostrum, J., Goedhart, J., In 't Hout, J., Hämmerling, G. J., Tanaka, S., Nadler, A., Schultz, C., Wright, M. D., Adjobo-Hermans, M. J. W., va Tags: STKE Research Articles Source Type: news

Research questions effectiveness of translocation conservation method
A DNA study of endangered greater prairie chickens in Illinois indicates that supplementing the dwindling population with birds from out of state did not improve genetic diversity. (Source: ScienceDaily Headlines)
Source: ScienceDaily Headlines - March 22, 2017 Category: Science Source Type: news

[Research Article] Phosphorylation of the exocyst protein Exo84 by TBK1 promotes insulin-stimulated GLUT4 trafficking
An inflammation-associated kinase also stimulates glucose uptake through plasma membrane translocation of GLUT4 in response to insulin. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - March 21, 2017 Category: Science Authors: Maeran Uhm, Merlijn Bazuine, Peng Zhao, Shian-Huey Chiang, Tingting Xiong, Sheelarani Karunanithi, Louise Chang, Alan R. Saltiel Source Type: news

Abnormal development of the brain in an intractable disease, thanatophoric dysplasia
In this study, by combining ferrets, whose brain is rather similar to that of humans, and unique technique developed by the present researchers, neuronal translocation along radial glial fibers to the cerebral cortex during fetal brain development has been discovered to be aberrant, which suggests the cause underlying TD. (Source: ScienceDaily Headlines)
Source: ScienceDaily Headlines - March 17, 2017 Category: Science Source Type: news

Abnormal development of the brain in an intractable disease, thanatophoric dysplasia
In this study, by combining ferrets, whose brain is rather similar to that of humans, and unique technique developed by the present researchers, neuronal translocation along radial glial fibers to the cerebral cortex during fetal brain development has been discovered to be aberrant, which suggests the cause underlying TD. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - March 17, 2017 Category: Global & Universal Source Type: news

[Perspective] Hematopoietic stem cells gone rogue
Cardiovascular disease is considered to be an aging-related disease and is the leading cause of death in the elderly in developed countries (1). As of 2013, 65% of deaths attributed to cardiovascular disease occurred among patients 75 years and older. A hallmark of aging is the accumulation of somatic DNA mutations in proliferative tissue. Although somatic mutations in the hematopoietic (blood cell) system are frequently observed in patients with hematological cancers, there is also a close correlation between hematopoietic somatic mutations and increased incidence of diabetes, atherosclerosis, and cardiovascular disease-r...
Source: ScienceNOW - February 24, 2017 Category: Science Authors: Yanfang Peipei Zhu Tags: Cardiovascular Disease Source Type: news

Targeted sequencing of FKBP5 in suicide attempters with bipolar disorder - Breen ME, Gaynor SC, Monson ET, de Klerk K, Parsons MG, Braun TA, DeLuca AP, Zandi PP, Potash JB, Willour VL.
FKBP5 is a critical component of the Hypothalamic-Pituitary-Adrenal (HPA) axis, a system which regulates our response to stress. It forms part of a complex of chaperones, which inhibits binding of cortisol and glucocorticoid receptor translocation to the n... (Source: SafetyLit)
Source: SafetyLit - January 5, 2017 Category: Global & Universal Tags: Ergonomics, Human Factors, Anthropometrics, Physiology Source Type: news

[Research Article] The receptor tyrosine kinase AXL mediates nuclear translocation of the epidermal growth factor receptor
The kinase AXL promotes cetuximab resistance by promoting the nuclear accumulation of EGFR. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - January 3, 2017 Category: Science Authors: Toni M. Brand, Mari Iida, Kelsey L. Corrigan, Cara M. Braverman, John P. Coan, Bailey G. Flanigan, Andrew P. Stein, Ravi Salgia, Jana Rolff, Randall J. Kimple, Deric L. Wheeler Source Type: news

[Editors' Choice] NIK sends mitochondria to the periphery
The kinase NIK promotes tumor cell invasion by stimulating the translocation of mitochondria to the cell periphery. (Source: Signal Transduction Knowledge Environment)
Source: Signal Transduction Knowledge Environment - January 3, 2017 Category: Science Authors: Nancy Gough (mailto:ngough at Source Type: news

[Perspective] Spying on the neighbors' pool
The structure and properties of the proton in water are of fundamental importance in many areas of chemistry and biology. The high mobility of the proton in an aqueous solution is understood in terms of its “hopping” between neighboring water molecules, as suggested by the two-century-old Grotthuss mechanism. The barrier for this process intimately depends on the proton's surrounding environment, which is manifested by the connectivity of the immediate hydrogen-bonding network as well as its dynamics caused by thermal fluctuations. On page 1131 of this issue, Wolke et al. (1) shed new light on the role that the...
Source: ScienceNOW - December 2, 2016 Category: Science Authors: Sotiris S. Xantheas Tags: Chemical Physics Source Type: news

[Research Article] A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1
Inhibition or genetic deletion of poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) is protective against toxic insults in many organ systems. The molecular mechanisms underlying PARP-1–dependent cell death involve release of mitochondrial apoptosis-inducing factor (AIF) and its translocation to the nucleus, which results in chromatinolysis. We identified macrophage migration inhibitory factor (MIF) as a PARP-1–dependent AIF-associated nuclease (PAAN). AIF was required for recruitment of MIF to the nucleus, where MIF cleaves genomic DNA into large fragments. Depletion of MIF, disruption of the AIF-MIF interaction, o...
Source: ScienceNOW - October 6, 2016 Category: Science Authors: Yingfei Wang Source Type: news

Critical But Overlooked: ICU Patients' Gut Bacteria
Paul Wischmeyer Our bodies are full of bacteria, and when we get sick, those microbial populations change. Hospitals monitor patients' bloodwork and vitals, so why not track the makeup of their microbiomes too? Paul Wischmeyer and his collaborators are conducting research that could allow them to do just that, opening the door for microbiome diagnostic indicators and probiotic measures to restore patients' normal bacterial signatures. We asked him about the research, and what he's learned so far. This text was edited for length. Read the full interview on ResearchGate News. ResearchGate: How did you first get involve...
Source: Science - The Huffington Post - September 6, 2016 Category: Science Source Type: news

OriGene's ALK UltraMAB® Antibody (OTI1A4) Outperform D5F3...
Recent Studies Validate High performance and Accurate Results for OriGene's UltraMAB® OTI1A4 as an Effective Screening Tool for ALK Translocation in Lung Adenocarcinomas(PRWeb April 14, 2016)Read the full story at (Source: PRWeb: Medical Pharmaceuticals)
Source: PRWeb: Medical Pharmaceuticals - April 15, 2016 Category: Pharmaceuticals Source Type: news

[Report] Activation of proto-oncogenes by disruption of chromosome neighborhoods
Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control of key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these structures and whether oncogene activation can occur via disruption of insulated neighborhood boundaries in cancer cells. We mapped insulated neighborhoods in T cell acute lymphoblastic leukemia (T-ALL) and found that tumor cell genomes contain recurrent microdeletions that eliminate the boundary sites of insulated nei...
Source: ScienceNOW - March 25, 2016 Category: Science Authors: Denes Hnisz Source Type: news