Browse Articles

TaTCP6 is required for efficient and balanced utilization of nitrate and phosphorus in wheat

Kosmotropic aqueous processing solution for green lithium battery cathode manufacturing

Two dimensional MoS2 accelerates mechanically controlled polymerization and remodeling of hydrogel

Topological identification and interpretation for single-cell epigenetic regulation elucidation in multi-tasks using scAGDE

Structural insights into the in situ assembly of clustered protocadherin γB4

Abstract Clustered protocadherins (cPcdhs) belong to the cadherin superfamily and play important roles in neural development. cPcdhs mediate homophilic adhesion and lead to self-avoidance and tiling by giving neurons specific identities in vertebrates. Structures and functions of cPcdhs have been studied extensively in past decades, but the mechanisms behind have not been fully understood. Here we investigate the in situ assembly of cPcdh-γB4, a member in the γ subfamily of cPcdhs, by electron tomography and find that the full length cPcdh-γB4 does not show regular organization at the adhesion interfaces. By contrast, cPcdh-γB4 lacking the intracellular domain can generate an ordered zigzag pattern between cells and the cis-interacting mode is different from the crystal packing of the ectodomain. We also identify the residues on the ectodomain that might be important for the zigzag pattern formation by mutagenesis. Furthermore, truncation mutants of the intracellular domain reveal different assembly patterns between cell membranes, suggesting that the intracellular domain plays a crucial role in the intermembrane organization of cPcdh-γB4. Taken together, these results suggest that both ectodomain and intracellular domain regulate the in situ assembly of cPcdh-γB4 for homophilic cell adhesion, thereby providing mechanistic insights into the functional roles of cPcdhs during neuronal wiring.

Anoctamin-1 is a core component of a mechanosensory anion channel complex in C. elegans

Abstract Mechanotransduction channels are widely expressed in both vertebrates and invertebrates, mediating various physiological processes such as touch, hearing and blood-pressure sensing. While previously known mechanotransduction channels in metazoans are primarily cation-selective, we identified Anoctamin-1 (ANOH-1), the C. elegans homolog of mammalian calcium-activated chloride channel ANO1/TMEM16A, as an essential component of a mechanosensory channel complex that contributes to the nose touch mechanosensation in C. elegans. Ectopic expression of either C. elegans or human Anoctamin-1 confers mechanosensitivity to touch-insensitive neurons, suggesting a cell-autonomous role of ANOH-1/ANO1 in mechanotransduction. Additionally, we demonstrated that the mechanosensory function of ANOH-1/ANO1 relies on CIB (calcium- and integrin- binding) proteins. Thus, our results reveal an evolutionarily conserved chloride channel involved in mechanosensory transduction in metazoans, highlighting the importance of anion channels in mechanosensory processes.

SRBD1 facilitates chromosome segregation by promoting topoisomerase IIα localization to mitotic chromosomes

Abstract Accurate sister chromatid segregation requires remodeling chromosome architecture, decatenation, and attachment to the mitotic spindle. Some of these events are initiated during S-phase, but they accelerate and conclude during mitosis. Here we describe SRBD1 as a histone and nucleic acid binding protein that prevents DNA damage in interphase cells, localizes to nascent DNA during replication and the chromosome scaffold in mitosis, and is required for chromosome segregation. SRBD1 inactivation causes micronuclei, chromatin bridges, and cell death. Inactivating SRBD1 immediately prior to mitotic entry causes anaphase failure, with a reduction in topoisomerase IIα localization to mitotic chromosomes and defects in properly condensing and decatenating chromosomes. In contrast, SRBD1 is not required to complete cell division after chromosomes are condensed. Strikingly, depleting condensin II reduces the severity of the anaphase defects in SRBD1-deficient cells by restoring topoisomerase IIα localization. Thus, SRBD1 is an essential genome maintenance protein required for mitotic chromosome organization and segregation.

Melanocortin 3 receptor regulates hepatic autophagy and systemic adiposity

Abstract Systemic lipid homeostasis requires hepatic autophagy, a major cellular program for intracellular fat recycling. Here, we find melanocortin 3 receptor (MC3R) regulates hepatic autophagy in addition to its previously established CNS role in systemic energy partitioning and puberty. Mice with Mc3r deficiency develop obesity with hepatic triglyceride accumulation and disrupted hepatocellular autophagosome turnover. Mice with partially inactive human MC3R due to obesogenic variants demonstrate similar hepatic autophagic dysfunction. In vitro and in vivo activation of hepatic MC3R upregulates autophagy through LC3II activation, TFEB cytoplasmic-to-nuclear translocation, and subsequent downstream gene activation. MC3R-deficient hepatocytes had blunted autophagosome-lysosome docking and lipid droplet clearance. Finally, the liver-specific rescue of Mc3r was sufficient to restore hepatocellular autophagy, improve hepatocyte mitochondrial function and systemic energy expenditures, reduce adipose tissue lipid accumulation, and partially restore body weight in both male and female mice. We thus report a role for MC3R in regulating hepatic autophagy and systemic adiposity.

Bioactive nanomotor enabling efficient intestinal barrier penetration for colorectal cancer therapy

Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity

Identification and characterization of cell niches in tissue from spatial omics data at single-cell resolution

Structure of an F-type phage tail-like bacteriocin from Listeria monocytogenes

Rhizobacteria protective hydrogel to promote plant growth and adaption to acidic soil

Digital aberration correction for enhanced thick tissue imaging exploiting aberration matrix and tilt-tilt correlation from the optical memory effect

Abstract Optical aberrations significantly impair microscopic image quality across various domains, including cell biology and histopathology diagnostics. Traditional adaptive optics techniques, such as wavefront shaping and guide star utilization, face challenges, especially in imaging biological tissues. Here, we introduce a computational adaptive optics approach tailored for optically thick samples. Utilizing the tilt-tilt correlation from the optical memory effect, our method detects phase differences in aberrations caused by small tilts in the incident waves. Experimental validation demonstrates our technique’s capacity to enhance imaging of thick human tissues under substantial aberration conditions using a transmission-mode holotomography setup. Remarkably, our approach works robustly against sample movement, which is essential for enhanced imaging accuracy in critical biomedical applications.

The anti-distortive polaron as an alternative mechanism for lattice-mediated charge trapping

Genetic regulation of TERT splicing affects cancer risk by altering cellular longevity and replicative potential

Abstract The chromosome 5p15.33 region, which encodes telomerase reverse transcriptase (TERT), harbors multiple germline variants identified by genome-wide association studies (GWAS) as risk for some cancers but protective for others. Here, we characterize a variable number tandem repeat within TERT intron 6, VNTR6-1 (38-bp repeat unit), and detect a strong link between VNTR6-1 alleles (Short: 24-27 repeats, Long: 40.5-66.5 repeats) and GWAS signals rs2242652 and rs10069690 within TERT intron 4. Bioinformatics analyses reveal that rs10069690-T allele increases intron 4 retention while VNTR6-1-Long allele expands a polymorphic G-quadruplex (G4, 35-113 copies) within intron 6, with both variants contributing to variable TERT expression through alternative splicing and nonsense-mediated decay. In two cell lines, CRISPR/Cas9 deletion of VNTR6-1 increases the ratio of TERT-full-length (FL) to the alternative TERT-β isoform, promoting apoptosis and reducing cell proliferation. In contrast, treatment with G4-stabilizing ligands shifts splicing from TERT-FL to TERT-β isoform, implicating VNTR6-1 as a splicing switch. We associate the functional variants VNTR6-1, rs10069690, and their haplotypes with multi-cancer risk and age-related telomere shortening. By regulating TERT splicing, these variants may contribute to fine-tuning cellular longevity and replicative potential in the context of stress due to tissue-specific endogenous and exogenous exposures, thereby influencing the cancer risk conferred by this locus.

Tissue factor-dependent colitogenic CD4+ T cell thrombogenicity is regulated by activated protein C signalling

Abstract Patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism (VTE), but the underlying mechanistic basis remains poorly defined. Here, we find that colitogenic CD4 + T cells express tissue factor (TF) and promote rapid TF-dependent plasma thrombin generation. TF + CD3 + CD4 + T cells are present in both the colons of mice with experimental colitis and blood and colonic tissue from patients with IBD. Expression of genes involved in regulating coagulation, including Protein C (PC; encoded by PROC) and its receptor ( PROCR) , are dysregulated in IBD patient gut biopsy tissues. Moreover, activated PC signalling reduces the procoagulant activity mediated by TF + CD4 + T cells. Our data thus identify TF-induced, colitogenic T cell-mediated thrombogenicity, and also demonstrate a new function for activated PC signalling in regulating T cell thrombo-inflammatory activity.

Unmasking the halide effect in diastereoselective Grignard reactions applied to C4´ modified nucleoside synthesis

Chiral plasmonic superlattices from template-assisted assembly of achiral nanoparticles

Abstract The creation of chiral plasmonic architectures combining templates with achiral plasmonic particles leads to strong chiroptical responses that can be finely tuned via the characteristics of the colloidal building blocks. Here we show how elastomeric molds, pre-patterned with a hexagonal array of triskelia motifs, can guide the assembly of ordinary noble metal colloids into chiral plasmonic architectures with strong dichroism values. Under normal incidence, the chiral arrays made with gold and silver colloids showed g-factors of 0.18 and 0.4, respectively. In all cases, increasing the size of the colloid allows tuning the optical properties of the structure in the VIS-NIR range. When a superstrate layer is deposited onto the structures, the extrinsic chirality response of the 2D superlattice is revealed and strongly amplified by the chiral motifs under oblique inspection, leading to g-factors of ± 1.2 at ± 14°. Finally, these chiral plasmonic resonances sustained by the triskelion array are used to produce circularly polarized photoluminescence from achiral organic dyes placed on top with up to 20% of dissymmetry.

Learning and actioning general principles of cancer cell drug sensitivity