Sp7 Action in the Skeleton: Its Mode of Action, Functions, and Relevance to Skeletal Diseases.

Osteoblast differentiation is a tightly regulated process in which key transcription factors (TFs) and their target genes constitute gene regulatory networks (GRNs) under the control of osteogenic signaling pathways. Among these TFs, Sp7 works as an osteoblast determinant critical for osteoblast differentiation. Following the identification of Sp7 and a large number of its functional studies, recent genome-scale analyses have made a major contribution to the identification of a "non-canonical" mode of Sp7 action as well as "canonical" ones.

Molecular encoding and synaptic decoding of context during salt chemotaxis in C. elegans.

Animals navigate toward favorable locations using various environmental cues. However, the mechanism of how the goal information is encoded and decoded to generate migration toward the appropriate direction has not been clarified. Here, we describe the mechanism of migration towards a learned concentration of NaCl in Caenorhabditis elegans.

Single-cell RNA sequencing unravels heterogeneity of skeletal progenitors and cell-cell interactions underlying the bone repair process.

Introduction: Activation of skeletal progenitors upon tissue injury and the subsequent cell fate specification are tightly coordinated in the bone repair process. Although known osteoimmunological signaling networks play important roles in the microenvironment of the bone defect sites, the molecular mechanism underlying the bone repair process has not been fully understood.

Methods: To better understand the behavior of the skeletal progenitors and the heterogeneity of the cells during bone repair at the microenvironmental level, we performed a combinatorial analysis consisting of lineage tracing for skeletal progenitors using the mouse line followed by single-cell RNA sequencing (scRNA-seq) analysis using a mouse model of calvarial bone repair.

DNA damage promotes HLA class I presentation by stimulating a pioneer round of translation-associated antigen production.

Antigen presentation by the human leukocyte antigen (HLA) on the cell surface is critical for the transduction of the immune signal toward cytotoxic T lymphocytes. DNA damage upregulates HLA class I presentation; however, the mechanism is unclear. Here, we show that DNA-damage-induced HLA (di-HLA) presentation requires an immunoproteasome, PSMB8/9/10, and antigen-transporter, TAP1/2, demonstrating that antigen production is essential.

Experimental Comparison of Bond Lifetime and Viscoelastic Relaxation in Transient Networks with Well-Controlled Structures.

We demonstrate an experimental comparison of the bond lifetime, estimated using surface plasmon resonance (SPR), and the viscoelastic relaxation time of transient networks with well-controlled structures (dynamically cross-linked Tetra-PEG gel). SPR and viscoelastic measurements revealed that the temperature dependences of the two characteristic times are in agreement, while the viscoelastic response is delayed with respect to the lifetime by a factor of 2-3, dependent on the network strand length. Polymers cross-linked by temporary interactions form transient networks, which show fascinating viscoelasticity with a single relaxation mode.

[Practical Education Program in Precision Cancer Medicine].

To train medical staffs capable of practicing precision cancer medicine, The University of Tokyo and 5 universities in the Kanto area planned the education program consisting of a variety of scientific fields including genomic science and have offered educational opportunities to graduate school students. The program aiming to facilitate students' knowledge and practical skills in this field is closely connected with the expert panel of cancer genomic medicine in which multidisciplinary medical staffs discuss novel therapeutic choices based on patients' genomic information in the incurable cases lacking standard treatments. Education programs focusing on the treatment of rare cancers as well as childhood and adolescent cancers are also based on multidisciplinary collaborations.

Sleep Satisfaction May Modify the Association between Metabolic Syndrome and BMI, Respectively, and Occupational Stress in Japanese Office Workers.

The association between obesity and psychological stress is ambiguous. The aim is to investigate the association between metabolic syndrome (MetS) and body mass index (BMI), respectively, with occupational stress among Japanese office workers. The study is a secondary analysis of the intervention group from a randomized controlled trial.

Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish.

Phospholipids in the membrane consist of diverse pairs of fatty acids bound to a glycerol backbone. The biological significance of the diversity, however, remains mostly unclear. Part of this diversity is due to lysophospholipid acyltransferases (LPLATs), which introduce a fatty acid into lysophospholipids.

Noncanonical imprinting sustains embryonic development and restrains placental overgrowth.

Genomic imprinting regulates parental origin-dependent monoallelic gene expression. It is mediated by either germline differential methylation of DNA (canonical imprinting) or oocyte-derived H3K27me3 (noncanonical imprinting) in mice. Depletion of Eed, an essential component of Polycomb repressive complex 2, results in genome-wide loss of H3K27me3 in oocytes, which causes loss of noncanonical imprinting (LOI) in embryos.

On-demand retrieval of cells three-dimensionally seeded in injectable thioester-based hydrogels.

Scaffold systems that can easily encapsulate cells and safely retrieve them at the desired time are important for the advancement of cell-based medicine. In this study, we designed and fabricated thioester-based poly(ethylene glycol) (PEG) hydrogels with injectability and on-demand degradability as new scaffold materials for cells. Hydrogels can be formed within minutes thioester cross-linking between PEG molecules and can be degraded under mild conditions in response to l-cysteine molecules through thiol exchange occurring at the thioester linkage.

Group IVE cytosolic phospholipase A limits psoriatic inflammation by mobilizing the anti-inflammatory lipid N-acylethanolamine.

Psoriasis is an inflammatory disorder characterized by keratinocyte hyper-proliferation and Th17-type immune responses. However, the roles of bioactive lipids and the regulation of their biosynthesis in this chronic skin disease are not fully understood. Herein, we show that group IVE cytosolic phospholipase A (cPLA ε/PLA2G4E) plays a counterregulatory role against psoriatic inflammation by producing the anti-inflammatory lipid N-acylethanolamine (NAE).

Old but New: Group IIA Phospholipase A as a Modulator of Gut Microbiota.

Among the phospholipase A (PLA) superfamily, the secreted PLA (sPLA) family contains 11 mammalian isoforms that exhibit unique tissue or cellular distributions and enzymatic properties. Current studies using sPLA-deficient or -overexpressed mouse strains, along with mass spectrometric lipidomics to determine sPLA-driven lipid pathways, have revealed the diverse pathophysiological roles of sPLAs in various biological events. In general, individual sPLAs exert their specific functions within tissue microenvironments, where they are intrinsically expressed through hydrolysis of extracellular phospholipids.

Transcription Factor Hematopoietically Expressed Homeobox Protein (Hhex) Negatively Regulates Osteoclast Differentiation by Controlling Cyclin-Dependent Kinase Inhibitors.

We investigated the role of hematopoietically expressed homeobox protein (Hhex) in osteoclast development. Trimethylation of lysine 27 of histone H3 at the -regulatory element of was maintained and that of lysine 4 was reduced during receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis, which was associated with a reduction of expression. Overexpression of in bone marrow-derived macrophages inhibited, whereas suppression promoted, RANKL-induced osteoclastogenesis in vitro.

Molecular connections between circadian clock and health/ageing.

For decades, considerable efforts have been expended for solving the molecular mechanisms of disease progression. An important clue to tackle this question is the circadian clock. Recent findings have uncovered previously unknown molecular connections between circadian clock and disease incidence, consequently causing the ageing process.

Use of anti-inhibin monoclonal antibody for increasing the litter size of mouse strains and its application to in vivo-genome editing technology†.

The litter size of mouse strains is determined by the number of oocytes naturally ovulated. Many attempts have been made to increase litter sizes by conventional superovulation regimens (e.g.

Silver-loaded carboxymethyl cellulose nonwoven sheet with controlled counterions for infected wound healing.

Carboxymethyl cellulose (CMC) is a promising material for moist wound healing, and silver loading onto CMC has been examined for anti-bacterial activity. In this study, we developed silver-loaded CMC nonwoven sheets with different counterions, namely sodium CMC (CMC-Na/Ag) and partially protonated CMC (CMC-H/Ag), to examine their anti-bacterial and wound-healing properties. Owing to the presence of counter protons, CMC-H/Ag showed slower water adsorption, dissolution, and Ag release than CMC-Na/Ag.

Eicosanoid signalling blockade protects middle-aged mice from severe COVID-19.

Coronavirus disease 2019 (COVID-19) is especially severe in aged populations. Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective, but vaccine efficacy is partly compromised by the emergence of SARS-CoV-2 variants with enhanced transmissibility. The emergence of these variants emphasizes the need for further development of anti-SARS-CoV-2 therapies, especially for aged populations.

Statistical Methods for Item Reduction in a Representative Lifestyle Questionnaire: Pilot Questionnaire Study.

Background: Reducing the number of items in a questionnaire while maintaining relevant information is important as it is associated with advantages such as higher respondent engagement and reduced response error. However, in health care, after the original design, an a posteriori check of the included items in a questionnaire is often overlooked or considered to be of minor importance. When conducted, this is often based on a single selected method.

Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics.

Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that causes millions of deaths every year. With the new understanding of the molecular mechanism(s) of disease progression, our knowledge about the disease is snowballing, leading to the evolution of many new therapeutic regimes and their successive trials. In the past few decades, various combinations of therapies have been proposed and are presently employed in the treatment of diverse cancers.

Secreted phospholipase A modifies extracellular vesicles and accelerates B cell lymphoma.

Extracellular vesicles (EVs) including exosomes act as intercellular communicators by transferring protein and microRNA cargoes, yet the role of EV lipids remains unclear. Here, we show that the pro-tumorigenic action of lymphoma-derived EVs is augmented via secreted phospholipase A (sPLA)-driven lipid metabolism. Hydrolysis of EV phospholipids by group X sPLA, which was induced in macrophages of Epstein-Barr virus (EBV) lymphoma, increased the production of fatty acids, lysophospholipids, and their metabolites.

Loss of calsyntenin paralogs disrupts interneuron stability and mouse behavior.

Calsyntenins (CLSTNs) are important synaptic molecules whose molecular functions are not fully understood. Although mutations in calsyntenin (CLSTN) genes have been associated with psychiatric disorders in humans, their function is still unclear. One of the reasons why the function of CLSTNs in the nervous system has not been clarified is the functional redundancy among the three paralogs.

Genetic diagnosis of pseudomyxoma peritonei originating from mucinous borderline tumor inside an ovarian teratoma.

Background: Pseudomyxoma peritonei is a rare disease condition mainly caused by primary mucinous tumors from the appendix and rarely from the ovary, such as when mucinous ovarian tumors arise from within a teratoma. Molecular analyses of pseudomyxoma from the appendix showed that KRAS and GNAS pathogenic variants are common genetic features of pseudomyxoma peritonei. However, the origin of the tumors is difficult to be identified via genetic variants alone.

Composite Clonal Analysis Reveals Transition of NSCLC Subtypes Through Accumulation of Gene Mutations: A Case Report.

We analyzed an EGFR-mutated lung cancer with a pathologic diagnosis of combined large cell neuroendocrine carcinoma with mixed adenocarcinoma subtypes. Targeted next-generation sequencing of each component suggested that mutations in , and and apparent loss of heterozygosity of and accompanied the transition of different adenocarcinoma subtypes. Additional gene mutations including , , and were noted during transdifferentiation from acinar adenocarcinoma to large cell neuroendocrine carcinoma.