Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structural step forward for NHEJ.

ABSTRACT: In a recent paper published in Cell Research, a cryo-EM structure reveals the interface between DNA-PKcs and the Ku70/80:DNA complex, together forming the DNA-dependent protein kinase holoenzyme in non-homologous DNA end joining. Insight from this structure suggests how an allosteric rearrangement of DNA-PKcs driven by Ku70/80:DNA binding regulates kinase activity in this largest member of a family of structurally homologous phosphoinositide 3-kinase-related protein kinases that includes mTOR, ATR, and ATM.

SUBMITTER: Watanabe G

PROVIDER: S-EPMC5674156 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Structural step forward for NHEJ.

Watanabe Go G Lieber Michael R MR Williams Dewight D

Cell research 20170919 11

In a recent paper published in Cell Research, a cryo-EM structure reveals the interface between DNA-PKcs and the Ku70/80:DNA complex, together forming the DNA-dependent protein kinase holoenzyme in non-homologous DNA end joining. Insight from this structure suggests how an allosteric rearrangement of DNA-PKcs driven by Ku70/80:DNA binding regulates kinase activity in this largest member of a family of structurally homologous phosphoinositide 3-kinase-related protein kinases that includes mTOR, A ...[more]

PMID: 28925388

Similar Datasets

Blinding Assessment: One Step Forward.

Project description: Not available

| S-EPMC8754420 | biostudies-literature

One step forward to personalized medicine?

Project description: Not available

| S-EPMC10652033 | biostudies-literature

Molecular Imaging of Pulmonary Fibrosis: Another Step Forward.

Project description: Not available

| S-EPMC7781130 | biostudies-literature

Self-monitoring of blood glucose: one STeP forward?

Project description:IntroductionIn times of short health care budgets, reimbursement for self-monitoring of blood glucose (SMBG) in diabetes patients without insulin treatment is subject to debate. The Structured Testing Program (STeP) trial found a positive correlation of test frequency and improved hemoglobin A1c (HbA1c) levels in poorly controlled type 2 diabetes patients not treated with insulin.MethodsA structured literature search for other clinical studies reporting on SMBG frequency was performed.ResultsThere is scarce evidence: three trials, including STeP, noted a significant and relevant correlation between testing frequency and improved HbA1c levels (FA effect), whereas two studies did not. The comparability between the identified studies is problematic.ConclusionFuture research should consider correlations between testing frequency and level of glycemic control. More emphasis should be placed on a structured approach to use SMBG and to address adherence to testing and therapy.

| S-EPMC3440172 | biostudies-literature

Step-forward randomization in multicenter emergency treatment clinical trials.

Project description:The authors present a new centralized randomization method for multicenter emergency treatment clinical trials. With this step-forward method, treatment randomization for the next subject is performed immediately after the enrollment of the current subject. This design ensures the readiness of the treatment assignment for each subject at the point of study enrollment, and it simultaneously provides effective control on treatment assignments balance and distributions of covariates. The authors also discuss procedures of the step-forward randomization method along with its implementation for two National Institute of Neurological Disorders and Stroke-funded multicenter acute stroke trials, one double-blinded and one open-labeled. Advantages and limitations are presented based on experience gained in these two trials.

| S-EPMC3052925 | biostudies-literature

Genotype-phenotype correlation in Pompe disease, a step forward.

Project description:Pompe's disease is a progressive myopathy caused by mutations in the lysosomal enzyme acid alphaglucosidase gene (GAA). A wide clinical variability occurs also in patients sharing the same GAA mutations, even within the same family.For a large series of GSDII patients we collected some clinical data as age of onset of the disease, presence or absence of muscular pain, Walton score, 6-Minute Walking Test, Vital Capacity, and Creatine Kinase. DNA was extracted and tested for GAA mutations and some genetic polymorphisms able to influence muscle properties (ACE, ACTN3, AGT and PPAR? genes).We compared the polymorphisms analyzed in groups of patients with Pompe disease clustered for their homogeneous genotype.We have been able to identify four subgroups of patients completely homogeneous for their genotype, and two groups homogeneous as far as the second mutation is defined "very severe" or "potentially less severe". When disease free life was studied we observed a high significant difference between groups. The DD genotype in the ACE gene and the XX genotype in the ACTN3 gene were significantly associated to an earlier age of onset of the disease. The ACE DD genotype was also associated to the presence of muscle pain.We demonstrate that ACE and ACTN3 polymorphisms are genetic factors able to modulate the clinical phenotype of patients affected with Pompe disease.

| S-EPMC4249737 | biostudies-literature

Neogastropod (Mollusca, Gastropoda) phylogeny: A step forward with mitogenomes.

Project description:The Neogastropoda (Mollusca, Gastropoda) encompass more than 15,000 described species of marine predators, including several model organisms in toxinology, embryology and physiology. However, their phylogenetic relationships remain mostly unresolved and their classification unstable. We took advantage of the many mitogenomes published in GenBank to produce a new molecular phylogeny of the neogastropods. We completed the taxon sampling by using an in-house bioinformatic pipeline to retrieve mitochondrial genes from 13 transcriptomes, corresponding to five families not represented in GenBank, for a final dataset of 113 taxa. Because mitogenomic data are prone to reconstruction artefacts, eight different evolutionary models were applied to reconstruct phylogenetic trees with IQTREE, RAxML and MrBayes. If the over-parametrization of some models produced trees with aberrant internal long branches, the global topology of the trees remained stable over models and softwares, and several relationships were revealed or found supported here for the first time. However, even if our dataset encompasses 60% of the valid families of neogastropods, some key taxa are missing and should be added in the future before proposing a revision of the classification of the neogastropods. Our study also demonstrates that even complex models struggle to satisfactorily handle the evolutionary history of mitogenomes, still leading to long-branch attractions in phylogenetic trees. Other approaches, such as reduced-genome strategies, must be envisaged to fully resolve the neogastropod phylogeny.

| S-EPMC9544082 | biostudies-literature

Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward.

Project description:Gastrointestinal stromal tumor (GIST) represents a paradigm for clinically effective targeted inhibition of oncogenic driver mutations in cancer. Five drugs are currently positioned as the standard of care for the treatment of advanced or metastatic GIST patients. This is the result of continuous, deep understanding of KIT and PDGFRA GIST oncogenic drivers as well as the resistance mechanisms associated to tumor progression. However, the complexity of GIST molecular heterogeneity is an evolving field, and critical questions remain open. Specifically, the clinical benefit of approved and/or investigated targeted agents is strikingly modest at advanced stages of the disease when compared with the activity of first-line imatinib. Ripretinib is a novel switch-pocket inhibitor with broad activity against KIT and PDGFRA oncoproteins and has recently demonstrated antitumoral activity across phase I to phase III clinical trials. Therefore, ripretinib has emerged as a new standard of care for advanced, multi-resistant GIST patients. Based on this data, the Food and Drug Administration has granted in 2020 the approval of ripretinib for GIST patients after progression to imatinib, sunitinib and regorafenib. This, in turn, constitutes a major breakthrough in sarcoma drug development, as there have not been new treatment approvals in GIST for nearly a decade. Herein, we provide a critical review on the preclinical and clinical development of ripretinib in GIST. Furthermore, we seek to assess the biological and clinical impact of this new standard of care on the course of the disease, aiming to provide an insight on future treatments strategies for the next coming years.

| S-EPMC7797597 | biostudies-literature

MSF Paediatric Days: a step forward in operationalising 'Humanitarian Paediatrics'.

Project description:Around the world, one in four children live in a country affected by conflict, political insecurity and disaster. Healthcare in humanitarian and fragile settings is challenging and complex to provide, particularly for children. Furthermore, there is a distinct lack of medical literature from humanitarian settings to guide best practice in such specific and resource-limited contexts. In light of these challenges, Médecins Sans Frontières (MSF), an international medical humanitarian organisation, created the MSF Paediatric Days with the aim of uniting field staff, policymakers and academia to exchange ideas, align efforts, inspire and share frontline research and experiences to advance humanitarian paediatric and neonatal care. This 2-day event takes place regularly since 2016. The fourth edition of the MSF Paediatric Days in April 2021 covered five main topics: essential newborn care, community-based models of care, paediatric tuberculosis, antimicrobial resistance in neonatal and paediatric care and the collateral damage of COVID-19 on child health. In addition, eight virtual stands from internal MSF initiatives and external MSF collaborating partners were available, and 49 poster communications and five inspiring short talks referred to as 'PAEDTalks' were presented. In conclusion, the MSF Paediatric Days serves as a unique forum to advance knowledge on humanitarian paediatrics and creates opportunities for individual and collective learning, as well as networking spaces for interaction and exchange of ideas.

| S-EPMC8477328 | biostudies-literature

One Step Forward, Two Steps Back: Bronchial Thermoplasty for Asthma.

Project description: Not available

| S-EPMC7874433 | biostudies-literature