Mostrando ítems 41-60 de 13833

    Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter. 

    Recent cryoEM studies elucidated details of the structural basis for the substrate selectivity and translocation of heteromeric amino acid transporters. However, Asc1/CD98hc is the only neutral heteromeric amino acid transporter that can function through facilitated diffusion, and the only one that...

    Molecular architecture and oligomerization of Candida glabrata Cdc13 underpin its telomeric DNA-binding and unfolding activity. 

    The CST complex is a key player in telomere replication and stability, which in yeast comprises Cdc13, Stn1 and Ten1. While Stn1 and Ten1 are very well conserved across species, Cdc13 does not resemble its mammalian counterpart CTC1 either in sequence or domain organization, and Cdc13 but not CTC1 ...

    APLF and long non-coding RNA NIHCOLE promote stable DNA synapsis in non-homologous end joining. 

    The synapsis of DNA ends is a critical step for the repair of double-strand breaks by non-homologous end joining (NHEJ). This is performed by a multicomponent protein complex assembled around Ku70-Ku80 heterodimers and regulated by accessory factors, including long non-coding RNAs, through poorly u...

    Structural basis for substrate specificity of heteromeric transporters of neutral amino acids. 

    Despite having similar structures, each member of the heteromeric amino acid transporter (HAT) family shows exquisite preference for the exchange of certain amino acids. Substrate specificity determines the physiological function of each HAT and their role in human diseases. However, HAT transport ...

    Long Noncoding RNA NIHCOLE Promotes Ligation Efficiency of DNA Double-Strand Breaks in Hepatocellular Carcinoma. 

    Long noncoding RNAs (lncRNA) are emerging as key players in cancer as parts of poorly understood molecular mechanisms. Here, we investigated lncRNAs that play a role in hepatocellular carcinoma (HCC) and identified NIHCOLE, a novel lncRNA induced in HCC with oncogenic potential and a role in the li...

    PD-L1 and HIF-2α Upregulation in Head and Neck Paragangliomas after Embolization. 

    Hypoxia activates pathways associated with tumor progression, metastatic spread, and alterations in the immune microenvironment leading to an immunosuppressive phenotype. In particular, the upregulation of PD-L1, a target for therapy with checkpoint inhibitors, is well-studied in several tumors. Ho...

    Tackling the implementation gap for the uptake of NGS and advanced molecular diagnostics into healthcare systems. 

    Next-generation sequencing (NGS) and liquid biopsy (LB) showed positive results in the fight against different cancer types. This paper aims to assess the uptake of advanced molecular diagnostics/NGS for quick and efficient genetic profiles of tumour cells. For that purpose, the European Alliance f...

    Structural basis of Focal Adhesion Kinase activation on lipid membranes. 

    Focal adhesion kinase (FAK) is a key component of the membrane proximal signaling layer in focal adhesion complexes, regulating important cellular processes, including cell migration, proliferation, and survival. In the cytosol, FAK adopts an autoinhibited state but is activated upon recruitment in...

    Assembly of the asymmetric human γ-tubulin ring complex by RUVBL1-RUVBL2 AAA ATPase. 

    The microtubule nucleator γ-tubulin ring complex (γTuRC) is essential for the function of microtubule organizing centers such as the centrosome. Since its discovery over two decades ago, γTuRC has evaded in vitro reconstitution and thus detailed structure-function studies. Here, we show that a comp...

    RPAP3 C-Terminal Domain: A Conserved Domain for the Assembly of R2TP Co-Chaperone Complexes. 

    The Rvb1-Rvb2-Tah1-Pih1 (R2TP) complex is a co-chaperone complex that works together with HSP90 in the activation and assembly of several macromolecular complexes, including RNA polymerase II (Pol II) and complexes of the phosphatidylinositol-3-kinase-like family of kinases (PIKKs), such as mTORC1 ...

    Recurrent Germline DLST Mutations in Individuals with Multiple Pheochromocytomas and Paragangliomas. 

    Pheochromocytomas and paragangliomas (PPGLs) provide some of the clearest genetic evidence for the critical role of metabolism in the tumorigenesis process. Approximately 40% of PPGLs are caused by driver germline mutations in 16 known susceptibility genes, and approximately half of these genes enc...

    Self-Organization of FtsZ Polymers in Solution Reveals Spacer Role of the Disordered C-Terminal Tail. 

    FtsZ is a self-assembling GTPase that forms, below the inner membrane, the mid-cell Z-ring guiding bacterial division. FtsZ monomers polymerize head to tail forming tubulin-like dynamic protofilaments, whose organization in the Z-ring is an unresolved problem. Rather than forming a well-defined str...

    Structure of the TELO2-TTI1-TTI2 complex and its function in TOR recruitment to the R2TP chaperone. 

    The R2TP (RUVBL1-RUVBL2-RPAP3-PIH1D1) complex, in collaboration with heat shock protein 90 (HSP90), functions as a chaperone for the assembly and stability of protein complexes, including RNA polymerases, small nuclear ribonucleoprotein particles (snRNPs), and phosphatidylinositol 3-kinase (PI3K)-l...

    Energetics and geometry of FtsZ polymers: nucleated self-assembly of single protofilaments. 

    Essential cell division protein FtsZ is an assembling GTPase which directs the cytokinetic ring formation in dividing bacterial cells. FtsZ shares the structural fold of eukaryotic tubulin and assembles forming tubulin-like protofilaments, but does not form microtubules. Two puzzling problems in Ft...

    Serum Amyloid A3 Fuels a Feed-Forward Inflammatory Response to the Bacterial Amyloid Curli in the Enteric Nervous System. 

    BACKGROUND & AIMS Mounting evidence suggests the gastrointestinal microbiome is a determinant of peripheral immunity and central neurodegeneration, but the local disease mechanisms remain unknown. Given its potential relevance for early diagnosis and therapeutic intervention, we set out to map the...

    The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem cells. 

    OBJECTIVE Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades ...

    Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context. 

    We have targeted a K-ras allele in mouse embryonic stem (ES) cells to express a K-Ras(V12) oncoprotein along with a marker protein (beta-geo) from a single bicistronic transcript. Expression of this oncogenic allele requires removal of a knocked in STOP transcriptional cassette by Cre recombinase. ...

    Brown adipose tissue-specific insulin receptor knockout shows diabetic phenotype without insulin resistance. 

    Although insulin regulates metabolism in both brown and white adipocytes, the role of these tissues in energy storage and utilization is quite different. Recombination technology using the Cre-loxP approach allows inactivation of the insulin receptor in a tissue-specific manner. Mice lacking insuli...

    Synergistic gene interactions control the induction of the mitochondrial uncoupling protein (Ucp1) gene in white fat tissue. 

    Among a selected group of mouse strains susceptible to dietary obesity, those with an enhanced capacity for Ucp1 and brown adipocyte induction in white fat preferentially lost body weight following adrenergic stimulation. Based on the generality of this mechanism for reducing obesity, a genetic ana...

    Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. 

    The mRNA levels for the mitochondrial uncoupling protein (UCP1) in fat tissues of A/J and C57BL/6J inbred strains of mice varied in a regional-specific manner after stimulation of adrenergic signaling by cold exposure or treatment with a beta3-adrenergic agonist. While the differences between strai...