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Новое в науке на 2022-10-04
Recent structures of the three-way complex formed by the scaffold protein SHOC2, the small G protein M-RAS and protein phosphatase 1 (PP1) provide a tantalizing insight into the activation of RAF, the oncogenic kinase and downstream effector of RAS that drives cell proliferation and survival.
2022-10-03
We used a hybrid machine learning systems (HMLS) strategy that includes the extensive search for the discovery of the most optimal HMLSs, including feature selection algorithms, a feature extraction...
2022-10-01
Sequencing of thousands of samples provides genetic variants with allele frequencies spanning a very large spectrum and gives invaluable insight into genetic determinants of diseases. Protecting the genetic...
2022-10-01
Artificial intelligence (AI) and machine learning (ML) have resulted in significant enthusiasm for their promise in healthcare. Despite this, prospective randomized controlled trials and successful clinical...
2022-09-30
To date, there are no effective treatments for most neurodegenerative diseases. Knowledge graphs can provide comprehensive and semantic representation for heterogeneous data, and have been successfully...
2022-09-30
Bioinformatics has gained much attention as a fast growing interdisciplinary field. Several attempts have been conducted to explore the field of bioinformatics by bibliometric analysis, however, such works...
2022-09-30
The ion channel NALCN regulates cell shedding in mice and enhances metastasis in mouse models of cancer. Disseminated cells without oncogenic mutations form normal structures at secondary sites, suggesting that cell shedding is a physiological process that is hijacked during tumorigenesis.
2022-09-29
The sc-linker is an analysis framework that combines genome-wide association study summary statistics, epigenomics and single-cell transcriptomes to identify disease-critical cell types and cellular processes across tissues and states.
2022-09-29
The high-resolution crystal structure of the SHOC2–MRAS–PP1C complex provides insights into the complex assembly, RAF dephosphorylation, MRAS selectivity versus canonical RAS isoforms, and the impact of Noonan syndrome mutations on complex formation.
2022-09-29
Multi-modal single-cell sequencing enables mapping of mutant and wild-type human hematopoietic stem and progenitor cells within the same person, to define cellular phenotypic and epigenetic perturbations associated with clonal hematopoiesis.
2022-09-26
Cross-disorder genetic association analyses identify five loci differentiating attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Individuals diagnosed with both ADHD and ASD are double-loaded with genetic risk for both disorders.
2022-09-26
Analyses of population-level variation in gene and enhancer expression in the human brain characterize the gene–enhancer regulome and the regulatory mechanisms of transcribed enhancers in neuropsychiatric diseases.
2022-09-26
Single-cell DNA sequencing data are generated from human neurons using primary template-directed amplification and analyzed using SCAN2, an improved genotyping tool. Indels are enriched in neuronal regulatory elements and may be deleterious.
2022-09-26
Oncogenes commonly amplify on circular extrachromosomal DNA (ecDNA) molecules in cancer. We show that ecDNA shapes each of the foundational principles of Darwinian evolution — random inheritance by descent, enhanced variation through random segregation, and selection — and thereby promotes rapid genome change, treatment resistance and poor outcomes for patients with cancer.
2022-09-23
Clonal expansion of DNMT3A-mutant hematopoietic stem cells is a risk factor for myeloid malignancies and other morbidities. A new study uses multi-modal single-cell genomics to characterize the myeloid differentiation bias of DNMT3A-mutated clones, and finds preferential hypomethylation of binding motifs for key transcriptional regulators.
2022-09-22
Increasing evidence links RNA methyltransferases to DNA damage repair. METTL16 is now shown to antagonize homologous recombination by preventing DNA-end resection via MRE11. Thus, METTL16 may represent a cancer vulnerability that can be used to identify patients able to benefit from combination therapies with DNA-damaging agents.
2022-09-22
Deeper insights into context-specific cancer cell states and the mechanisms that underlie the phenotypic plasticity of different cancer types are key to tackling tumor formation, therapy resistance and recurrence after therapy.
2022-09-22
Therapeutic resistance in prostate cancer can be driven by lineage plasticity, but the mechanisms behind this are unclear, and therapies to prevent or reverse the process are nonexistent. A new study reveals the JAK/STAT signaling axis as a driver of lineage plasticity with tremendous therapeutic potential.
2022-09-22
The identification of tumor-reactive T cells using phenotypic markers is now well established in treatment-naive tumors. It is unclear, however, whether these markers can also be useful after immune checkpoint blockade (ICB). A new study finds that CXCL13 expression robustly identifies tumor-reactive T cells before and after ICB and is associated with treatment response.
2022-09-22
Zhang and colleagues analyze single-cell data from patients treated with immunotherapy in five cancer types and find that CXCL13-expressing subsets are implicated in response to treatment in the CD8+ and CD4+ T cell compartments.
2022-09-22
Lou and colleagues describe the role of METTL16 in homologous recombination repair and demonstrate that PARP inhibition may be beneficial in the treatment of PDAC that is characterized by high METTL16.
2022-09-22
Schmatko et al. review the application of artificial intelligence to digitized histopathology for cancer diagnosis, prognosis and classification and discuss its potential utility in the clinic and broader implications for cancer research and care.
2022-09-22
Sengupta et al. show that the mesenchymal cell state in neuroblastoma is associated with heightened immunogenicity and anti-tumor immune responses compared with the adrenergic state, which is linked to sensitivity to immunotherapy in preclinical models.
2022-09-22
The mechanisms by which translesion DNA polymerases mediate DNA repair are incompletely understood. A new study shows that Escherichia coli DNA polymerase IV is concentrated at the sites of arrested DNA synthesis by an interaction with SSB, the major single-stranded DNA-binding protein, specifically at stalled but not ongoing replication forks.
2022-09-20
Escherichia coli SSB enriches Pol IV polymerase at lesion-stalled replication forks, promoting translesion synthesis. Loss of this enrichment increases repriming of DNA synthesis, revealing a pivotal role of SSB in the pathway choice of stalled replication forks.
2022-09-20
The Braun lab shows that the conserved nuclear membrane protein Lem2 interacts with the MTREC complex of the nuclear-exosome pathway to promote recruitment and degradation of ncRNAs and meiotic transcripts at the nuclear periphery in Schizosaccharomyces pombe.
2022-09-19
