GPI transamidase complex is required for primordial germ cell migration and development in zebrafish.

Proteins without transmembrane domains could be anchored to the cell surface for regulating various biological processes when covalently linked to glycosylphosphatidylinositol (GPI) molecules by the GPI transamidase (GPIT) complex. However, it remains poorly understood whether and how the GPIT complex affects primordial germ cell (PGC) development. In this study, we report the important roles of GPI transamidase in PGC migration and development in zebrafish embryos.

DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection.

DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2.

CryoSeek II: Cryo-EM analysis of glycofibrils from freshwater reveals well-structured glycans coating linear tetrapeptide repeats.

Despite the recent breakthrough in structure determination and prediction of proteins, the structural investigation of carbohydrates remains a challenge. Here, we report the cryo-EM analysis of a glycofibril found in the freshwater in the Tsinghua Lotus Pond. The fibril, which we name TLP-4, is made of a linear chain of tetrapeptide repeats coated with >4 nm thick glycans.

Hypoxia drives the formation of lung micropapillary adenocarcinoma-like structure through hypoxia-inducible factor-1α.

Micropapillary adenocarcinoma (MPC) is an aggressive histological subtype of lung adenocarcinoma (LUAD). MPC is composed of small clusters of cancer cells exhibiting inverted polarity. However, the mechanism underlying its formation is poorly understood.

Cas12e orthologs evolve variable structural elements to facilitate dsDNA cleavage.

Exceptionally diverse type V CRISPR-Cas systems provide numerous RNA-guided nucleases as powerful tools for DNA manipulation. Two known Cas12e nucleases, DpbCas12e and PlmCas12e, are both effective in genome editing. However, many differences exist in their in vitro dsDNA cleavage activities, reflecting the diversity in Cas12e's enzymatic properties.

Downregulation of semaphorin 4A in keratinocytes reflects the features of non-lesional psoriasis.

Psoriasis is a multifactorial disorder mediated by IL-17-producing T cells, involving immune cells and skin-constituting cells. Semaphorin 4A (Sema4A), an immune semaphorin, is known to take part in T helper type 1/17 differentiation and activation. However, Sema4A is also crucial for maintaining peripheral tissue homeostasis and its involvement in skin remains unknown.

Dynamic properties of isotropic DMPC/DHPC bicelles: Insights from solution NMR and MD simulations.

Bicelles, an artificial disk-shaped lipid bilayer, are commonly used for the structural and functional characterization of membrane-bound proteins in an environment similar to that in intracellular membranes. Because the dynamics of the lipids that constitute bicelles exert a significant impact on the structure and function of the inserted proteins, we investigated the mobility of lipid molecules in bicelles composed of DMPC (14:0 PC) and DHPC (06:0 PC) using solution NMR and MD calculations. C R relaxation experiments for the acyl groups demonstrated that increasing bicelle sizes limit the rotational diffusion of acyl chain H-C bonds in DMPC.

An intermediate open structure reveals the gating transition of the mechanically activated PIEZO1 channel.

PIEZO1 is a mechanically activated cation channel that undergoes force-induced activation and inactivation. However, its distinct structural states remain undefined. Here, we employed an open-prone PIEZO1-S2472E mutant to capture an intermediate open structure.

A conserved human CD4+ T cell subset recognizing the mycobacterial adjuvant, trehalose monomycolate.

Mycobacterium tuberculosis causes human tuberculosis. As mycobacteria are protected by thick lipid cell wall, humans have developed immune responses against diverse mycobacterial lipids. Most of these immunostimulatory lipids are known as adjuvants acting through innate immune receptors, such as C-type lectin receptors.

Lipid mediator palmitoylethanolamide (PEA) inhibits pathogenic T cell differentiation in vitro and in vivo.

Lipid mediator, palmitoylethanolamide (PEA) has recently attracted attention as a potential therapeutic option for various inflammatory autoimmune diseases. It has been reported that PEA exerts an inhibitory effect on inflammation triggered by PRRs, particularly Toll-like receptors expressed on myeloid antigen-presenting cells. However, the precise role of PEA in T cell development and function has not yet been elucidated.

Novel Choline-Deficient and 0.1%-Methionine-Added High-Fat Diet Induces Burned-Out Metabolic-Dysfunction-Associated Steatohepatitis with Inflammation by Rapid Immune Cell Infiltration on Male Mice.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a progressive liver disorder that possesses metabolic dysfunction and shows steatohepatitis. Although the number of patients is globally increasing and many clinical studies have developed medicine for MASLD, most of the studies have failed due to low efficacy. One reason for this failure is the lack of appropriate animal disease models that reflect human MASLD to evaluate the potency of candidate drugs.

A Self-Cascading Catalytic Therapy and Antigen Capture Scaffold-Mediated T Cells Augments for Postoperative Brain Immunotherapy.

The recruitment of T lymphocytes holds great potential for suppressing the most aggressive glioblastoma (GBM) recurrence with immunotherapy. However, the phenomenon of immune privilege and the generally low immunogenicity of vaccines often reduce the presence of lymphocytes within brain tumors, especially in brain tumor recurrence clusters. In this study, an implantable self-cascading catalytic therapy and antigen capture scaffold (CAS) that can boost catalytic therapy efficiency at post-surgery brain tumor and capture the antigens via urethane-polyethylene glycol-polypropylene glycol (PU-EO-PO) segments are developed for postoperative brain immunotherapy.

Gum Arabic Enhances Hair Follicle-Targeting Drug Delivery of Minoxidil Nanocrystal Dispersions.

In this study, we attempted to enhance the delivery of minoxidil (MXD) nanocrystals into hair follicles for efficacious hair growth treatment. We applied a bead milling method and designed an MXD nanocrystal dispersion containing methylcellulose (MC) and gum arabic (GA), termed MG-MXD@NP, with a particle size of 110 nm. In vivo studies in C57BL/6 mice showed that MG-MXD@NP improved MXD delivery to the skin tissue, hair bulges, and hair bulbs, resulting in earlier and superior hair growth compared with a commercially available MXD lotion (Riup 5%, CA-MXD).

Lonidamine, a Novel Modulator for the BvgAS System of Bordetella Species.

The Gram-negative bacteria Bordetella pertussis, B. parapertussis, and B. bronchiseptica cause respiratory diseases in various mammals.

Ciliary length regulation by intraflagellar transport in zebrafish.

How cells regulate the size of their organelles remains a fundamental question in cell biology. Cilia, with their simple structure and surface localization, provide an ideal model for investigating organelle size control. However, most studies on cilia length regulation are primarily performed on several single-celled organisms.

Self-regulation of MGAT4A and MGAT4B activity toward glycoproteins through interaction of lectin domain with their own -glycans.

-Acetylglucosaminyltransferases-IVa (GnT-IVa or MGAT4A) and -IVb (MGAT4B) are glycosyltransferase isozymes synthesizing the β1,4-GlcNAc branch in -glycans, a glycan structure involved in diabetes. These enzymes uniquely have a non-catalytic lectin domain, which selectively recognizes the GnT-IV product -glycan branch, but the role of this lectin domain has remained unclear. Here, using UDP-Glo enzyme assays, we discovered that this domain is required for activity toward glycoprotein substrates but not toward free glycans.

Analysis of antigen specificity of Treg cell clonotypes expanded upon SARS-CoV-2 infection.

The pandemic outbreak of SARS-CoV-2 has threatened human health worldwide. Among protective immune reactions, T cell responses are diverse among individuals, which is related to the differences in severity. A T cell subset, regulatory T (Treg) cells, is crucial for limiting excessive immune responses.

Mechanical and thermodynamic routes to the liquid-liquid interfacial tension and mixing free energy by molecular dynamics.

In this study, we carried out equilibrium molecular dynamics (EMD) simulations of the liquid-liquid (LL) interface between two different Lennard-Jones components with varying miscibility, where we examined the relation between the interfacial tension and the free energy to completely isolate the two liquids using both a mechanical and thermodynamic approach. Using the mechanical approach, we obtained a stress distribution around a quasi-one-dimensional EMD system with a flat LL interface. From the stress distribution, we calculated the LL interfacial tension based on Bakker's equation, which uses the stress anisotropy around the interface, and measured how it varied with miscibility.

Structure and assembly of the dystrophin glycoprotein complex.

The dystrophin glycoprotein complex (DGC) has a crucial role in maintaining cell membrane stability and integrity by connecting the intracellular cytoskeleton with the surrounding extracellular matrix. Dysfunction of dystrophin and its associated proteins results in muscular dystrophy, a disorder characterized by progressive muscle weakness and degeneration. Despite the important roles of the DGC in physiology and pathology, its structural details remain largely unknown, hindering a comprehensive understanding of its assembly and function.

Raman microscopy of cryofixed biological specimens for high-resolution and high-sensitivity chemical imaging.

Raman microscopy is an emerging molecular imaging technology, yet its signal-to-noise ratio (SNR) in measurements of biological specimens is severely limited because of the small cross section of Raman scattering. Here, we present Raman imaging techniques of cryofixed specimens to overcome SNR limitations by enabling long exposure of specimens under highly stabilized low-temperature conditions. The observation of frozen specimens in a cryostat at a constant low temperature immediately after rapid freezing enabled the improvement of SNR and enhanced the spatial and spectral resolution.

CAR-NK cells derived from cord blood originate mainly from CD56CD7CD34HLA-DRLin NK progenitor cells.

Cord blood (CB)-derived chimeric antigen receptor (CAR)-natural killer (NK) cells targeting CD19 have been shown to be effective against B cell malignancies. While human CD56 NK cells can be expanded , NK cells can also be differentiated from hematopoietic progenitor cells. It is still unclear whether CAR-NK cells originate from mature NK cells or NK progenitor cells in CB.