Dynamic behavior of cell-cell adhesion factors in collective cell migration.

Collective cell migration is a fundamental process underlying various biological phenomena, including embryonic development and cancer cell invasion. The cohesive yet flexible movement of cell collectives largely depends on the coordinated regulation of cell-cell and cell-substrate adhesions. In this review, we summarize the regulation of key cell-cell junction components, such as cadherins and zonula occludens proteins during collective cell migration, with a particular focus on the recently discovered multifaceted roles of ZO-1 in both cell-cell and cell-substrate interactions.

Thermal gradient ring for analysis of temperature-dependent behaviors involving TRP channels in mice.

There are a lot of temperature-sensitive proteins including transient receptor potential (TRP) channels. Some TRP channels are temperature receptors having specific activation temperatures in vitro that are within the physiological temperature range. Mice deficient in specific TRP channels show abnormal thermal behaviors, but the role of TRP channels in these behaviors is not fully understood.

The microcephaly-associated transcriptional regulator AUTS2 cooperates with Polycomb complex PRC2 to produce upper-layer neurons in mice.

AUTS2 syndrome is characterized by intellectual disability and microcephaly, and is often associated with autism spectrum disorder, but the underlying mechanisms, particularly concerning microcephaly, remain incompletely understood. Here, we analyze mice mutated for the transcriptional regulator AUTS2, which recapitulate microcephaly. Their brains exhibit reduced division of intermediate progenitor cells (IPCs), leading to fewer neurons and decreased thickness in the upper-layer cortex.

Titin fragment is a sensitive biomarker in Duchenne muscular dystrophy model mice carrying full-length human dystrophin gene on human artificial chromosome.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations of the dystrophin gene, which spans 2.4 Mb on the X chromosome. Creatine kinase (CK) activity in blood and titin fragment levels in urine have been identified as biomarkers in DMD to monitor disease progression and evaluate therapeutic intervention.

Mice carrying the full-length human immunoglobulin loci produce antigen-specific human antibodies with the lambda light chain.

The development of antibody drugs through animal immunization typically requires the humanization of host antibodies to address concerns about immunogenicity in humans. However, employing an animal model capable of producing human antibodies presents the opportunity to develop antibody drugs without the need for humanization. Despite the ratio of human immunoglobulin (Ig) κ to Igλ usage being approximately 60%:40%, the majority of approved antibody therapeutics are kappa antibodies, and the development of lambda antibodies as therapeutic agents has lagged behind.

Spatially ordered recruitment of fast muscles in accordance with movement strengths in larval zebrafish.

In vertebrates, skeletal muscle comprises fast and slow fibers. Slow and fast muscle cells in fish are spatially segregated; slow muscle cells are located only in a superficial region, and comprise a small fraction of the total muscle cell mass. Slow muscles support low-speed, low-force movements, while fast muscles are responsible for high-speed, high-force movements.

Genome-scale evolution in local populations of wild chimpanzees.

Analysis of genome-scale evolution has been difficult in large, endangered animals because opportunities to collect high-quality genetic samples are limited. There is a need for novel field-friendly, cost-effective genetic techniques. This study conducted an exome-wide analysis of a total of 42 chimpanzees (Pan troglodytes) across six African regions, providing insights into population discrimination techniques.

Cell cycle-dependent regulation of CRISPR-Cas9 repetitive activation by anti-CRISPR and Cdt1 fusion in the CRISPRa system.

CRISPR-Cas9 is a widely used genome-editing tool. We previously developed a method with improved homology-directed repair efficiency and reduced off-target effects by utilizing a fusion protein of AcrIIA4, a Cas9 inhibitor, and Cdt1, which accumulates in the G1 phase and activates Cas9 only in the S/G2 phase. However, it is unknown whether Cas9 inhibition by AcrIIA4 + Cdt1 occurs repeatedly in the G1 phase as the cell cycle progresses.

Molecular tag for promoting -glycan maturation in the cargo receptor-mediated secretion pathway.

MCFD2 and ERGIC-53 form a cargo receptor complex that plays a crucial role in transporting specific glycoproteins, including blood coagulation factor VIII, from the endoplasmic reticulum to the Golgi apparatus. We have demonstrated that MCFD2 recognizes a 10-amino-acid sequence in factor VIII, thereby facilitating its efficient transport. Moreover, the secretion of biopharmaceutical recombinant glycoproteins, such as erythropoietin, can be enhanced by tagging them with this sequence, which we have termed the "passport sequence" (PS).

Human artificial chromosome carrying R-spondin1 and IL-22 expression cassettes in rejuvenated MSCs enhances therapeutic efficacy in ulcerative colitis model mice.

Ulcerative colitis (UC) is an incurable intestinal disease, with current treatments mainly focused on inflammation control and, in severe cases, surgical resection. Recent studies have highlighted the need for new therapies that promote tissue regeneration. R-spondin-1 (RSPO1) and interleukin-22 (IL-22) have shown anti-inflammatory and regenerative effects in UC models, but have short half-lives and poor targeting abilities.

Novel role of zinc-finger protein 518 in heterochromatin formation on α-satellite DNA.

Aneuploidy is caused by chromosomal missegregation and is frequently observed in cancers and hematological diseases. Therefore, it is important to understand the molecular mechanisms underlying chromosomal segregation. The centromere's intricate structure is crucial for proper chromosome segregation, with heterochromatin at the pericentromeric α-satellites playing a key role.

Non-thermal atmospheric pressure plasma-irradiated cysteine protects cardiac ischemia/reperfusion injury by preserving supersulfides.

Ischemic heart disease is the main global cause of death in the world. Abnormal sulfide catabolism, especially hydrogen sulfide accumulation, impedes mitochondrial respiration and worsens the prognosis after ischemic insults, but the substantial therapeutic strategy has not been established. Non-thermal atmospheric pressure plasma irradiation therapy is attracted attention as it exerts beneficial effects by producing various reactive molecular species.

Generation of Monosomy 21q Human iPS Cells by CRISPR/Cas9-Mediated Interstitial Megabase Deletion.

Missing an entire chromosome or chromosome arm in normal diploid cells has a deleterious impact on cell viability, which may contribute to the development of specific birth defects. Nevertheless, the effects of chromosome loss in human cells have remained unexplored due to the lack of suitable model systems. Here, we developed an efficient, selection-free approach to generate partial monosomy in human induced pluripotent stem cells (iPSCs).

γ-Secretase Cleaves Bifunctional Fatty Acid-Conjugated Small Molecules with Amide Bonds in Mammalian Cells.

Connecting two small molecules, such as ligands, fluorophores, or lipids, together via a linker with amide bonds is a widely used strategy to generate synthetic bifunctional molecules for various biological and biomedical applications. Such bifunctional molecules have been used in live-cell experiments under the assumption that they should be stable in cells. However, we recently found that a membrane-targeting bifunctional molecule, composed of a lipopeptide and the small-molecule ligand trimethoprim, referred to as mgcTMP, underwent amide-bond cleavage in mammalian cells.

Possible roles of CAHS proteins from Tardigrade in osmotic stress tolerance in mammalian cells.

Anhydrobiosis, a phenomenon in which organisms survive extreme dehydration by entering a reversible ametabolic state, is a remarkable example of survival strategies. This study focuses on anhydrobiosis in tardigrades, which are known for their resilience to severe environmental conditions. Tardigrades utilize several protective mechanisms against desiccation, notably the constitutive expression of cytoplasmic abundant heat soluble (CAHS) proteins in Ramazzottius varieornatus.

Nonequilibrium Molecular Dynamics Method to Generate Poiseuille-Like Flow between Lipid Bilayers.

There are various flows inside and outside cells in vivo. Nonequilibrium molecular dynamics (NEMD) simulation is a useful tool for understanding the effects of these flows on the dynamics of biomolecules. We propose an NEMD method to generate a Poiseuille-like flow between lipid bilayers.

Physical Isolation of Single Protein Molecules within Well-Defined Coordination Cages to Enhance Their Stability.

Encapsulation of a single protein within a confined space can lead to distinct properties compared to bulk solutions, but controlling the number of encapsulated proteins and their environment remains challenging. This study demonstrates the encapsulation of single proteins within well-defined, tunable cavities of self-assembled coordination cages, thereby enhancing protein stability. Within uniform cavities of size-tunable coordination cages, 15 different proteins of varying sizes (3-6 nm in diameter) and properties (e.

Infrared laser-induced gene expression in single cells characterized by quantitative imaging in Physcomitrium patens.

A spatiotemporal understanding of gene function requires the precise control of gene expression in each cell. Here, we use an infrared laser-evoked gene operator (IR-LEGO) system to induce gene expression at the single-cell level in the moss Physcomitrium patens by heating a living cell with an IR laser and thereby activating the heat shock response. We identify the laser irradiation conditions that provide higher inducibility with lower invasiveness by changing the laser power and irradiation duration.

Spatiotemporal control of transgene expression using an infrared laser in the crustacean Daphnia magna.

The crustacean Daphnia magna is an emerging model for ecological and toxicological genomics. However, the lack of methods for spatial and temporal control of gene expression has impaired the elucidation of molecular mechanisms underlying responses to environments in vivo. Here we report local activation of the hsp70 promoter-driven gene cassette in D.

Single-Molecule Kinetic Observation of Antibody Interactions with Growing Amyloid β Fibrils.

Understanding the dynamic assembly process of amyloid β (Aβ) during fibril formation is essential for developing effective therapeutic strategies against Alzheimer's disease. Here, we employed high-speed atomic force microscopy to observe the growth of Aβ fibrils at the single-molecule level, focusing specifically on their interaction with anti-Aβ antibodies. Our findings show that fibril growth consists of intermittent periods of elongation and pausing, which are dictated by the alternating addition of Aβ monomers to protofilaments.