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CRISPR-Cas enzymes are increasingly entering clinical trials for gene therapies but can sometimes alter DNA off-target. We present an approach to modify the guide RNA to effectively eliminate off-target activity for target sequences of interest.
Protein-protein interaction networks of coronary artery disease (CAD) risk genes in human vascular cells are enriched for genetic variants associated with CAD and can be used to guide future research into the molecular pathogenesis of CAD.
Despite ample investigation on cis-regulatory alterations in evolution, the contribution of these effects to environmental adaptation is poorly understood. Ballinger and colleagues dissected the cis- and trans-regulatory impact on gene expression associated with the adaptation of house mice to temperate and tropical climates, highlighting potential mechanisms acting at a short evolutionary timescale.
Using an experimental evolution approach, this study provides direct evidence that herbivory-induced responses contribute to rapid adaptive evolution to herbivores in plants.
A sex chromosome identification method for ancient DNA revealed six individuals who lived with chromosomal aneuploidies in Britain from ~ 2,500 to 250 years ago. Genomic and osteological information was combined to shed light on their lives.
The subthalamic nucleus is a highly evolutionary conserved brain region. Emerging studies reveal spatio-molecular heterogeneity leading to improved understanding of the organization of the STN and targeting for specific neurological disorders.
Ex vivo electrophysiology reveals that vagus firing patterns differ between aged and young mice, and that the aminosterol, squalamine, changed aged neuronal firing to a younger neuron phenotype. Squalamine, but not sertraline, increased firing rates in the aged vagus.
The dengue viral protein NS5 interacts with human STAT2 in a conformational selection mechanism, and structural analysis reveals that subtle amino acid variation in NS5 proteins underpins their species-specific host interactions.
CCDC88B physically interacts with ARHGEF2 and RASAL3; defective mice show dampened neuroinflammation, altered susceptibility to colitis and altered DCs motility by modulating RHOA, with ARHGEF2 and RASAL3 acting in opposite regulatory fashions.
Autologous serum- and feeder-free cultured epithelium showcases comparable efficacy, increased safety over serum- and feeder-dependent epithelium, revealing the role of LAMB3+ keratinocytes and ZNF90+ fibroblasts in vitiligo.
The physical properties of the cells and proteins surrounding a tumor play a crucial role in determining the spread of the cancer. How they change cancer cells to suppress the immune response against them is an interesting question addressed in a recent study from Liu et al., which describes how increased stiffness of the tissue around the tumor decreases the amount of a protein—cyclic GMP-AMP synthase—in cancer cells, ultimately blocking the immune response to cancer.
As a monogamous species, the prairie vole is a common model for social neuroscience. Gustison and colleagues mapped a whole-brain histological atlas of the prairie vole and used this atlas to identify a neural network of pair-bonding behaviour. The study reveals coordinated neural networks in mated pairs and highlights the influence of social bonding on neural processing in the adult prairie vole brain.
Nanopores have the potential to revolutionize the field of protein sequencing, but due to the biochemical complexity of polypeptide sequences, they have remained mostly theoretical. In recent work, Sauciuc et al. engineer the protein nanopore CytK to produce an electroosmotic force capable of translocating unfolded polypeptides regardless of their charge distributions, an important step toward single-file protein nanopore sequencing.
Plant organs shift their directional growth in response to environmental stimuli through tropisms. Arabidopsis roots exhibit positive hydrotropism (towards water) and negative phototropism (away from light). In a recent study, Pang and colleagues demonstrated that root phototropism is regulated by the activity of two proteins in the elongation zone that also play essential roles in hydrotropism.
Applying MSBP to cryo-sample can protect particles from air-water interface, leading to an enhanced particle distribution and behavior. This simple approach offers an alternative strategy to optimize cryo-samples for single-particle cryo-EM studies
A combined colonic histomorphology, 16 S rRNA gene sequencing, and untargeted metabolomics analysis on D-ribose-fed mice suggest that oral D-ribose caused intestinal epithelial barrier impairment and microbiota-gut-brain axis dysbiosis.