Role of endothelial microRNA-23 clusters in angiogenesis in vivo.

The capillary network is distributed throughout the body, and its reconstruction is induced under various pathophysiological conditions. MicroRNAs are small noncoding RNAs that regulate gene expression via posttranscriptional mechanisms and are involved in many biological functions, including angiogenesis. Previous studies have shown that each microRNA of miR-23 clusters, composed of the miR-23a cluster (miR-23a~27a~24-2) and miR-23b cluster (miR-23b~27b~24-1), regulates angiogenesis in vitro.

Does the prenatal bisphenol A exposure alter DNA methylation levels in the mouse hippocampus?: An analysis using a high-sensitivity methylome technique.

Background: There is still considerable debate about the effects of exposure to bisphenol A (BPA) an endocrine disrupter at low doses. Recently, many studies using animal models have shown that prenatal BPA exposure induces behavioral and neuronal disorders due to epigenetic changes in the brain. However, striking evidence of epigenomic changes has to be shown.

The anatomical pathway from the mesodiencephalic junction to the inferior olive relays perioral sensory signals to the cerebellum in the mouse.

Key Points: Perioral tactile signals are transmitted via the infraorbital nerve (ION) to trigeminal nuclei. Each cerebellar Purkinje cell (PC) receives this signal as complex spikes (CSs) via a climbing fibre (CF) emerging from the inferior olive (IO). The anatomical pathway from trigeminal nuclei to the IO is not clearly identified.

Small Delivery Vehicles of siRNA for Enhanced Cancer Targeting.

Small interfering RNA (siRNA) drugs have been considered to treat various diseases in major organs. However, siRNA drugs developed for cancer therapy are hindered from proceeding to the clinic. To date, various delivery formulations have been developed from cationic lipids, polymers, and/or inorganic nanoparticles for systemic siRNA delivery to solid tumors.

Development of human-derived hemoglobin-albumin microspheres as oxygen carriers using Shirasu porous glass membrane emulsification.

Novel hemoglobin-based artificial oxygen carriers are necessary in tissue engineering. We developed human hemoglobin (hHb) and albumin (HSA)-based microspheres using Shirasu porous glass (SPG) membrane emulsification. The obtained microspheres had a uniform size with an average diameter of 15.

Tuned Density of Anti-Tissue Factor Antibody Fragment onto siRNA-Loaded Polyion Complex Micelles for Optimizing Targetability into Pancreatic Cancer Cells.

Antibody fragment (Fab')-installed polyion complex (PIC) micelles were constructed to improve targetability of small interfering RNA (siRNA) delivery to pancreatic cancer cells. To this end, we synthesized a block copolymer of azide-functionalized poly(ethylene glycol) and poly(l-lysine) and prepared PIC micelles with siRNA. Then, a dibenzylcyclooctyne (DBCO)-modified antihuman tissue factor (TF) Fab' was conjugated to azido groups on the micellar surface.

Apolipoprotein M Protects Lipopolysaccharide-Treated Mice from Death and Organ Injury.

Objective: High-density lipoprotein (HDL) has been epidemiologically shown to be associated with the outcome of sepsis. One potential mechanism is that HDL possesses pleiotropic effects, such as anti-apoptosis, some of which can be ascribed to sphingosine 1-phosphate (S1P) carried on HDL via apolipoprotein M (apoM). Therefore, the aim of this study was to elucidate the roles of apoM/S1P in the consequent lethal conditions of sepsis, such as multiple organ failure caused by severe inflammation and/or disseminated intravascular coagulation.

XRCC3 polymorphism is associated with hypertension-induced left ventricular hypertrophy.

Deficiency of X-ray repair cross-complementing protein 3 (XRCC3), a DNA-damage repair molecule, and the 241Met variant of XRCC3 have been reported to increase endoreduplication, which induces polyploidy. The aims of this study were to determine the impact of the XRCC3 polymorphism on the incidence of hypertension-induced left ventricular hypertrophy (LVH) and to investigate the mechanisms underlying any potential relationship. Patients undergoing chronic hemodialysis (n = 77) were genotyped to assess for the XRCC3 Thr241Met polymorphism.

Preventive effect of on squamous cell carcinoma of mouse skin involving down-regulation of prostaglandin E synthetic pathway.

Hyperproduced prostaglandin E by cyclooxygenase-2 and microsomal prostaglandin E synthase-1 evokes several pathophysiological responses such as inflammation and carcinogenesis. Our recent study demonstrated that extract suppressed the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 and induced apoptosis in lung carcinoma A549 cells. In the present study, we investigated the effects of on squamous cell carcinoma of mouse skin.

Fabrication of calcium phosphate-loaded carboxymethyl cellulose non-woven sheets for bone regeneration.

Calcium phosphate-loaded carboxymethyl cellulose non-woven sheets (CMC/CaP sheet) were fabricated and their potential to induce in vitro osteoblast differentiation and in vivo bone regeneration were investigated. The CMC/CaP sheets were prepared by alternately soaking protonated-CMC non-woven sheets in CaCl and NaHPO aqueous solutions. Because of its slow water uptake rate, the protonated-CMC was successfully loaded with a mixed phase of brushite and hydroxyapatite.

An Ethylenediamine-based Switch to Render the Polyzwitterion Cationic at Tumorous pH for Effective Tumor Accumulation of Coated Nanomaterials.

Polyzwitterions are employed as coating polymers for biomaterials to induce an antifouling property on the surface. Fine-tuning the betaine structure switches the antifouling property to be interactive with anionic tissue constituents in response to a tumorous pH gradient. The ethylenediamine moiety in the carboxybetaine enabled stepwise protonation and initiated the di-protonation process around tumorous pH (6.

Oocyte-activating capacity of fresh and frozen-thawed spermatids in the common marmoset (Callithrix jacchus).

The common marmoset (Callithrix jacchus) represents a promising nonhuman primate model for the study of human diseases because of its small size, ease of handling, and availability of gene-modified animals. Here, we aimed to devise reproductive technology for marmoset spermatid injection using immature males for a possible rapid generational turnover. Spermatids at each step could be identified easily by their morphology under differential interference microscopy: thus, early round spermatids had a round nucleus with a few nucleolus-like structures and abundant cytoplasm, as in other mammals.

Vocalization as a novel endpoint of atypical attachment behavior in 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed infant mice.

Mammalian attachment behaviors, such as crying, are essential for infant survival by receiving food, protection, and warmth from caregivers. Ultrasonic vocalization (USV) of infant rodents functions to promote maternal proximity. Impaired USV emission has been reported in mouse models of autism spectrum disorder, suggesting that USV is associated with higher brain function.

Calcineurin knockout mice show a selective loss of small spines.

Calcineurin is required for long-term depression and activity-dependent spine shrinkage, and calcineurin mutations have been identified in patients with schizophrenia. Moreover, mice with conditional knockout of calcineurin B (CNB-KO) exhibit behavioral abnormalities suggestive of schizophrenia. Changes in the dendritic spines of these mice, however, have not been investigated.

AIM associated with the IgM pentamer: attackers on stand-by at aircraft carrier.

Circulating immunoglobulin M (IgM) exists in a pentameric form, possessing a polyreactive nature that responds not only to foreign antigens but also to autoantigens; thus, it is involved in both beneficial and detrimental immune responses, including protection from infection and the progression of autoimmunity. On the other hand, IgM also behaves as a carrier of the apoptosis inhibitor of macrophage (AIM) protein, storing a large amount of the inactivated form of AIM in the blood through this association. Under different disease conditions, AIM can dissociate from IgM locally or systemically to exert its function, inducing the removal of various biological debris such as excess fat, bacteria, cancer cells or dead cell debris.

Temporal requirement of dystroglycan glycosylation during brain development and rescue of severe cortical dysplasia via gene delivery in the fetal stage.

Congenital muscular dystrophies (CMDs) are characterized by progressive weakness and degeneration of skeletal muscle. In several forms of CMD, abnormal glycosylation of α-dystroglycan (α-DG) results in conditions collectively known as dystroglycanopathies, which are associated with central nervous system involvement. We recently demonstrated that fukutin, the gene responsible for Fukuyama congenital muscular dystrophy, encodes the ribitol-phosphate transferase essential for dystroglycan function.

Molecular characterization of feline melanocortin 4 receptor and melanocortin 2 receptor accessory protein 2.

Melanocortin 4 receptor (MC4R), which is a member of the G protein-coupled receptor (GPCR) family, mediates regulation of energy homeostasis upon the binding of α-melanocyte-stimulating hormone (α-MSH) in the central nervous system (CNS). Melanocortin 2 receptor accessory protein 2 (MRAP2) modulates the function of MC4R. We performed cDNA cloning of cat MC4R and MRAP2 and characterized their amino acid sequences, mRNA expression patterns in cat tissues, protein-protein interactions, and functions.

Direct cell-cell contact between mature osteoblasts and osteoclasts dynamically controls their functions in vivo.

Bone homeostasis is regulated by communication between bone-forming mature osteoblasts (mOBs) and bone-resorptive mature osteoclasts (mOCs). However, the spatial-temporal relationship and mode of interaction in vivo remain elusive. Here we show, by using an intravital imaging technique, that mOB and mOC functions are regulated via direct cell-cell contact between these cell types.

Detection of dioxin-induced demethylation of mouse gene promoter by a new labeling method for short DNA fragments possessing 5'-methylcytosine at the end.

Environmental factors stimulate alteration of DNA methylation level. Investigation of the genome-wide DNA methylation status is important for environmental health studies. We here designed a genomic DNA amplification and labeling protocol using a methylation-sensitive restriction enzyme I.

3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation.

DNA double-strand breaks (DSBs) induced by ionising radiation are considered the major cause of genotoxic mutations and cell death. While DSBs are dispersed throughout chromatin after X-rays or γ-irradiation, multiple types of DNA damage including DSBs, single-strand breaks and base damage can be generated within 1-2 helical DNA turns, defined as a complex DNA lesion, after high Linear Energy Transfer (LET) particle irradiation. In addition to the formation of complex DNA lesions, recent evidence suggests that multiple DSBs can be closely generated along the tracks of high LET particle irradiation.

The Impact of "Possible Patients" on Phenotyping Algorithms: Electronic Phenotype Algorithms Can Only Be Reproduced by Sharing Detailed Annotation Criteria.

Phenotyping is an automated technique for identifying patients diagnosed with a particular disease based on electronic health records (EHRs). To evaluate phenotyping algorithms, which should be reproducible, the annotation of EHRs as a gold standard is critical. However, we have found that the different types of EHRs cannot be definitively annotated into CASEs or CONTROLs.

Injectable Hydrogel with Slow Degradability Composed of Gelatin and Hyaluronic Acid Cross-Linked by Schiff's Base Formation.

We developed an injectable gelatin/hyaluronic acid hydrogel with slow degradability, which consisted of carbohydrazide-modified gelatin (Gel-CDH) and hyaluronic acid monoaldehyde (HA-mCHO). Gel-CDH/HA-mCHO hydrogels were degraded much more slowly in phosphate-buffered saline than the other Schiff's base cross-linked gelatin/hyaluronic acid hydrogels that were comprised of native gelatin, adipic acid dihydrazide-modified gelatin, or hyaluronic acid dialdehyde because of stable Schiff's base formation between aldehyde and carbohydrazide groups, and suppression of ring-opening oxidation by monoaldehyde modification. This prolonged degradation would be suitable for inducing angiogenesis.

Identification of quantitative trait loci associated with the susceptibility of mouse spermatozoa to cryopreservation.

Although it is known that the susceptibility of mouse spermatozoa to freezing-thawing varies greatly with genetic background, the underlying mechanisms remain to be elucidated. In this study, to map genetic regions responsible for the susceptibility of spermatozoa to freezing-thawing, we performed in vitro fertilization using spermatozoa from recombinant inbred mice derived from the C57BL/6J and DBA/2J strains, whose spermatozoa showed distinct fertilization abilities after freezing. Genome-wide interval mapping identified two suggestive quantitative trait loci (QTL) associated with fertilization on chromosomes 1 and 11.

Enhanced Intracellular Delivery of siRNA by Controlling ATP-Responsivity of Phenylboronic Acid-Functionalized Polyion Complex Micelles.

Intracellular delivery of small interfering RNA (siRNA) is a long-standing challenge in oligonucleotide therapeutics. Herein, adenosine triphosphate (ATP)-responsive polyion complex micelles assembled from poly(ethylene glycol)-block-poly(l-lysine) (PEG-PLys) bearing 4-carboxy-3-fluorophenylboronic acid (FPBA) moiety in the PLys side chains (FPBA micelle) for the delivery of cholesterol-modified siRNA (Chol-siRNA) are described. The pK of FPBA moiety is 7.