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Новое в науке на 2023-04-02
The cryo-EM structure of a natural AlkB–AlkG fusion from Fontimonas thermophila reveals the mechanistic basis for its selectivity towards, and functionalization of, alkane terminal C–H groups. AlkB contains an alkane entry tunnel and a diiron active site, and AlkG docks through electrostatic interactions and transfers electrons to the diiron center for catalysis.
2023-03-31
The human microbiome plays a critical role in maintaining human health. Due to the recent advances in high-throughput sequencing technologies, the microbiome profiles present in the human body have become...
2023-03-31
Cluster analysis is utilized frequently in scientific theory and applications to separate data into groups. A key assumption in many clustering algorithms is that the data was generated from a population...
2023-03-31
Telomere length is an important determinant of cellular aging and disease risk, but the genetics of telomere length control in humans is unclear. A genome-wide CRISPR screen has now identified a central role for thymidine nucleotide metabolism in the regulation of telomere length, which has implications for the diagnosis and treatment of disease.
2023-03-30
Fluorine nuclear magnetic resonance spectroscopy of the stimulatory heterotrimeric G protein reveals a conformational landscape shaped by interactions with nucleotides, the lipid bilayer and a G-protein-coupled receptor.
2023-03-30
Here, using cryo-EM and biochemical methods, the authors demonstrate that second messenger (p)ppGpp regulates the bacterial RNA polymerase by binding to a site that is functionally relevant during transcriptional elongation but not initiation. Moreover, they demonstrate that binding to that site bears functional implications for nucleotide excision DNA repair and genome stability.
2023-03-30
Alkane monooxygenase (AlkB) enables diverse microorganisms to hydrolyze alkanes as their sole carbon and energy source. Liu and colleagues reveal how AlkB orients an alkane to its active site and performs a selective terminal C–H bond hydroxylation.
2023-03-30
Clinical utility of T cell engagers (TCEs) in cancer immunotherapy for solid tumors is hampered by on-target off-tumor activity and dose-limiting adverse events. A study now proposes a solution to tackle these challenges through the design and preclinical characterization of extended half-life TCEs that are conditionally activated in the tumor microenvironment.
2023-03-30
Schellenberger and colleagues engineer masked, conditionally active T-cell engagers targeting tumor antigens and CD3 and show potent, protease-dependent antitumor activity in mouse models, as well as safety in non-human primates.
2023-03-30
Automatic cell tracking methods enable practitioners to analyze cell behaviors efficiently. Notwithstanding the continuous development of relevant software, user-friendly visualization tools have room for...
2023-03-29
Although targeting cancer cells on the basis of tissue-specific expression of key factors is an important strategy in precision oncology, few such therapies exist. Chemical screening now identifies YC-1 as a tissue-specific anti-cancer compound that is activated in the liver by the sulfotransferase enzyme SULT1A1.
2023-03-28
Cancer biology is the cornerstone on which much of modern cancer research is based. Continuing to explore the intricacies of this multilayered foundational scientific area is essential.
2023-03-28
High-throughput and selective detection of organelles in immunofluorescence images is an important but demanding task in cell biology. The centriole organelle is critical for fundamental cellular processes,...
2023-03-28
A new study deciphers the origin and evolution of childhood neuroblastoma using genome sequencing data, mathematical models and statistical inference, showing how neuroblastoma evolution is an accurate predictor of outcome.
2023-03-27
How histone modifications are reprogrammed through germline development in plants is poorly understood. We found that H3K27me3 and H3K4me3 are extensively reprogrammed throughout the development of Arabidopsis male gametophyte. This reprogramming leads to widespread chromatin bivalency and selective removal of H3K27me3 marks from key developmental regulators in sperm.
2023-03-27
Analysis of multiple tumor types, cancer cell lines and adult tissues identifies tumor-specific transposable-element-chimeric transcripts. Mass spectrometry data confirm that many are translated and subsequently located on the extracellular surface of cancer cells, highlighting potential immunogenic therapies.
2023-03-27
Somatic evolutionary analysis of neuroblastoma, a pediatric tumor, proposes a common fetal time of origin. Notably, high-risk tumors exhibit early genomic instability and prolonged evolution, and this evolutionary duration predicts clinical outcomes.
2023-03-27
Gabapentinoid drugs are widely used for pain, epilepsy and mental disorders. Chen et al. report the structure of a gabapentin-bound brain and heart calcium channel, revealing the gabapentin binding site and isoform-selective binding determinants.
2023-03-27
Using atomic force microscopy, Pan et al. show that cyclic nucleotide-gated ion channel SthK, which can be differentially activated by cAMP and cGMP, binds both cyclic nucleotides but only cAMP can access a deep-bound state that could be essential for cAMP-dependent channel activation.
2023-03-27
Su et al. find that BACH1 specifically interacts with the p53 (R175H) hotspot mutant. This has double oncogenic effects, leading to increased expression of the pro-metastatic targets of BACH1 as well as blockage of its capacity to activate ferroptosis.
2023-03-27
Park et al. show that in the process of metastasis, dying tumor cells enhance the outgrowth of their surviving counterparts via nuclear expulsion, resulting in an extracellular DNA–protein complex that activates RAGE receptors on tumor cells.
2023-03-27
Genome-wide CRISPR screening identifies thymidine nucleotide metabolism as a key regulator of human telomere length. Thymidine supplementation promotes telomere elongation in cells derived from patients with telomere biology disorders.
2023-03-23
Genetic lineage tracing in mice shows that endocardium-derived fibroblasts preferentially proliferate in response to pressure overload. Ablation of these cells alleviates cardiac fibrosis and reduces functional decline after pressure overload injury.
2023-03-23
Adjusting for common variant polygenic scores improves yield in gene-based rare variant association tests for quantitative traits, particularly when using sparse mixed models or simple linear models as an alternative to dense mixed-model approaches.
2023-03-23
Tsirigotaki et al. unveil how adipokine Leptin induces trimerization of the Leptin receptor to form a cytokine-receptor assembly critical to body weight regulation, immunity, fertility and cancer.
2023-03-23
Zhang et al. describe structures, diverse function and subunit-specific pharmacology of three major GluN2C- and GluN2D-incorporated NMDA receptors known to exist in the brain.
2023-03-23
Saur and colleagues provide an overview of single-cell analyses in pancreatic cancer and discuss their implications for our understanding of heterogeneity and plasticity in the tumor and its microenvironment.
2023-03-23
A study of the immune microenvironment of estrogen receptor-positive (ER+) invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) identifies pro-tumor and anti-tumor macrophages as key players that can potentially influence disease outcome.
2023-03-21
