Efficient marmoset genome engineering by autologous embryo transfer and CRISPR/Cas9 technology.

Genetic engineering of non-human primates, which are most closely related to humans, has been expected to generate ideal animal models for human genetic diseases. The common marmoset (Callithrix jacchus) is a non-human primate species adequate for the production of genetically modified animals because of their small body size and high reproductive capacity. Autologous embryo transfer (AET) is routinely utilized in assisted reproductive technologies for humans but not for experimental animals.

Atrophy of White Adipose Tissue Accompanied with Decreased Insulin-Stimulated Glucose Uptake in Mice Lacking the Small GTPase Rac1 Specifically in Adipocytes.

Insulin stimulates glucose uptake in adipose tissue and skeletal muscle by inducing plasma membrane translocation of the glucose transporter GLUT4. Although the small GTPase Rac1 is a key regulator downstream of phosphoinositide 3-kinase (PI3K) and the protein kinase Akt2 in skeletal muscle, it remains unclear whether Rac1 also regulates glucose uptake in white adipocytes. Herein, we investigated the physiological role of Rac1 in white adipocytes by employing adipocyte-specific knockout (adipo--KO) mice.

Scapular Angiomatoid Fibrous Histiocytoma with EWSR1-CREB1 Fusion in an Adult Patient.

Background: Angiomatoid fibrous histiocytoma (AFH) is a rare intermediate malignant tumor that arises mainly in soft tissues, especially in the superficial extremities of patients younger than 30 years. There have been a few reports of AFH arising from sites other than soft tissue, including bone, and unusual site and age make it difficult to diagnose this rare tumor. .

Claims-based algorithms for common chronic conditions were efficiently constructed using machine learning methods.

Identification of medical conditions using claims data is generally conducted with algorithms based on subject-matter knowledge. However, these claims-based algorithms (CBAs) are highly dependent on the knowledge level and not necessarily optimized for target conditions. We investigated whether machine learning methods can supplement researchers' knowledge of target conditions in building CBAs.

α-Tocopherol transfer protein (α-TTP).

α-Tocopherol transfer protein (α-TTP) is so far the only known protein that specifically recognizes α-tocopherol (α-Toc), the most abundant and most biologically active form of vitamin E, in higher animals. α-TTP is highly expressed in the liver where α-TTP selects α-Toc among vitamin E forms taken up via plasma lipoproteins and promotes its secretion to circulating lipoproteins. Thus, α-TTP is a major determinant of plasma α-Toc concentrations.

AIM/CD5L attenuates DAMPs in the injured brain and thereby ameliorates ischemic stroke.

The sterile inflammation caused by damage-associated molecular patterns (DAMPs) worsens the prognosis following primary injury such as ischemic stroke. However, there are no effective treatments to regulate DAMPs. Here, we report that AIM (or CD5L) protein reduces sterile inflammation by attenuating DAMPs and that AIM administration ameliorates the deleterious effects of ischemic stroke.

Mechanism of chromosome rearrangement arising from single-strand breaks.

Chromosome rearrangements, which are structural chromosomal abnormalities commonly found in human cancer, result from the misrejoining between two or more DNA double-strand breaks arising at different genomic regions. Consequently, chromosome rearrangements can generate fusion genes that promote tumorigenesis. The mechanisms of chromosome rearrangement have been studied using exogenous double-strand break inducers, such as radiation and nucleases.

Mast Cell-Specific Deletion of Group III Secreted Phospholipase A Impairs Mast Cell Maturation and Functions.

Tissue-resident mast cells (MCs) have important roles in IgE-associated and -independent allergic reactions. Although microenvironmental alterations in MC phenotypes affect the susceptibility to allergy, understanding of the regulation of MC maturation is still incomplete. We previously reported that group III secreted phospholipase A (sPLA-III) released from immature MCs is functionally coupled with lipocalin-type prostaglandin D (PGD) synthase in neighboring fibroblasts to supply a microenvironmental pool of PGD, which in turn acts on the PGD receptor DP1 on MCs to promote their proper maturation.

Mesenchymal stromal cells in the bone marrow niche consist of multi-populations with distinct transcriptional and epigenetic properties.

Although multiple studies have investigated the mesenchymal stem and progenitor cells (MSCs) that give rise to mature bone marrow, high heterogeneity in their morphologies and properties causes difficulties in molecular separation of their distinct populations. In this study, by taking advantage of the resolution of the single cell transcriptome, we analyzed Sca-1 and PDGFR-α fraction in the mouse bone marrow tissue. The single cell transcriptome enabled us to further classify the population into seven populations according to their gene expression profiles.

CRISPR/Cas9-based genetic screen of SCNT-reprogramming resistant genes identifies critical genes for male germ cell development in mice.

Male germ cells undergo complex developmental processes eventually producing spermatozoa through spermatogenesis, although the molecular mechanisms remain largely elusive. We have previously identified somatic cell nuclear transfer-reprogramming resistant genes (SRRGs) that are highly enriched for genes essential for spermatogenesis, although many of them remain uncharacterized in knockout (KO) mice. Here, we performed a CRISPR-based genetic screen using C57BL/6N mice for five uncharacterized SRRGs (Cox8c, Cox7b2, Tuba3a/3b, Faiml, and Gm773), together with meiosis essential gene Majin as a control.

Computational roles of intrinsic synaptic dynamics.

Conventional theories assume that long-term information storage in the brain is implemented by modifying synaptic efficacy. Recent experimental findings challenge this view by demonstrating that dendritic spine sizes, or their corresponding synaptic weights, are highly volatile even in the absence of neural activity. Here, we review previous computational works on the roles of these intrinsic synaptic dynamics.

Easy and quick (EQ) sperm freezing method for urgent preservation of mouse strains.

Cryopreservation of mouse spermatozoa is widely used for the efficient preservation and safe transport of valuable mouse strains. However, the current cryopreservation method requires special containers (plastic straws), undefined chemicals (e.g.

Impacts of chromatin dynamics and compartmentalization on DNA repair.

The proper spatial organization of DNA, RNA, and proteins is critical for a variety of cellular processes. The genome is organized into numerous functional units, such as topologically associating domains (TADs), the formation of which is regulated by both proteins and RNA. In addition, a group of chromatin-bound proteins with the ability to undergo liquid-liquid phase separation (LLPS) can affect the spatial organization and compartmentalization of chromatin, RNA, and proteins by forming condensates, conferring unique properties to specific chromosomal regions.

Positive and negative roles of lipids in mast cells and allergic responses.

Mast cells are a central immune cell population that are crucial in allergic responses. They secrete granule contents and cytokines and produce a panel of lipid mediators in response to FcεRI-dependent or independent stimuli. Leukotrienes and prostaglandins derived from ω6 arachidonic acid, or specialized pro-resolving lipid mediators derived from ω3 eicosapentaenoic and docosahexaenoic acids, exert pleiotropic effects on various cells in the tissue microenvironment, thereby positively or negatively regulating allergic responses.

mGluR1 signaling in cerebellar Purkinje cells: Subcellular organization and involvement in cerebellar function and disease.

The cerebellum is essential for the control, coordination, and learning of movements, and for certain aspects of cognitive function. Purkinje cells are the sole output neurons in the cerebellar cortex and therefore play crucial roles in the diverse functions of the cerebellum. The type 1 metabotropic glutamate receptor (mGluR1) is prominently enriched in Purkinje cells and triggers downstream signaling pathways that are required for functional and structural plasticity, and for synaptic responses.

Coronavirus-specific antibody production in middle-aged mice requires phospholipase A2G2D.

Worse outcomes occur in aged compared with young populations after infections with respiratory viruses, including pathogenic coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2), and are associated with a suboptimal lung milieu ("inflammaging"). We previously showed that a single inducible phospholipase, PLA2G2D, is associated with a proresolving/antiinflammatory response in the lungs, and increases with age. Survival was increased in naive Pla2g2d-/- mice infected with SARS-CoV resulting from augmented respiratory dendritic cell (rDC) activation and enhanced priming of virus-specific T cells.

Spine dynamics in the brain, mental disorders and artificial neural networks.

In the brain, most synapses are formed on minute protrusions known as dendritic spines. Unlike their artificial intelligence counterparts, spines are not merely tuneable memory elements: they also embody algorithms that implement the brain's ability to learn from experience and cope with new challenges. Importantly, they exhibit structural dynamics that depend on activity, excitatory input and inhibitory input (synaptic plasticity or 'extrinsic' dynamics) and dynamics independent of activity ('intrinsic' dynamics), both of which are subject to neuromodulatory influences and reinforcers such as dopamine.

Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia.

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing.

Automatic Classification of Electronic Nursing Narrative Records Based on Japanese Standard Terminology for Nursing.

In Japan, nursing records are not easily put to secondary use because nursing documentation is not standardized. In recent years, electronic health records have necessitated the creation of Japanese nursing terminology. The purpose of this study was to develop and evaluate an automatic classification system for narrative nursing records using natural language processing technology and machine learning.

Implications of the germline variants of DNA damage response genes detected by cancer precision medicine for radiological risk communication and cancer therapy decisions.

Large-scale cancer-associated gene testing is now being rapidly incorporated into clinical settings, and is leading to incidental identification of the germline variants present in cancer patients. Because many cancer susceptibility genes are related to DNA damage response and repair, the variants may reflect not only the susceptibility to cancer but also the genetically defined radiation sensitivity of the patients and their relatives. When the presence of a certain germline variant increases the risk for developing radiation toxicity or radiation-induced secondary cancers, it will greatly influence the clinical decision-making.

Neurons expressing the aryl hydrocarbon receptor in the locus coeruleus and island of Calleja major are novel targets of dioxin in the mouse brain.

The aryl hydrocarbon receptor (AhR) acts as a receptor that responds to ligands, including dioxin. The AhR-ligand complex translocates from the cytoplasm into the nucleus to induce gene expression. Because dioxin exposure impairs cognitive and neurobehavioral functions, AhR-expressing neurons need to be identified for elucidation of the dioxin neurotoxicity mechanism.