A novel mechanism of thrombocytopenia by PS exposure through TMEM16F in sphingomyelin synthase 1 deficiency.

Sphingomyelin synthase 1 (SMS1) contributes to the generation of membrane sphingomyelin (SM) and affects SM-mediated physiological functions. Here, we describe the hematologic phenotypes, such as reduced circulating platelets and dysfunctional hemostasis, in SMS1-deficient (SMS1-KO) mice. SMS1-KO mice display pathologic manifestations related to idiopathic thrombocytopenia (ITP), including relatively high amounts of peripheral blood reticulated platelets, enhanced megakaryopoiesis in the bone marrow and spleen, and splenomegaly.

Effect of Dy substitution in the giant magnetocaloric properties of HoB.

Recently, a massive magnetocaloric effect near the liquefaction temperature of hydrogen has been reported in the ferromagnetic material HoB. Here we investigate the effects of Dy substitution in the magnetocaloric properties of Ho Dy B alloys ( = 0, 0.3, 0.

Pressure-induced superconductivity in SnSbTe.

Here we firstly report the pressure-induced superconductivity in phase change materials SnSbTe. Single crystals of SnSbTe were grown using a conventional melting-down method. The resistance under pressure was measured using an originally designed diamond anvil cell with boron-doped diamond electrodes.

Crystal Growth, Structural Analysis, and Pressure-Induced Superconductivity in a AgInSe Single Crystal Explored by a Data-Driven Approach.

A high-throughput first-principles calculation-assisted data-driven approach based on an inorganic materials database named AtomWork was performed to explore new superconducting materials. Specific band structures of a small band gap and flat band at band edges were used in a screening procedure. Among the candidates studied, we focused on AgInSe, which shows a high density of state at the Fermi level.

Data-driven exploration of new pressure-induced superconductivity in PbBiTe.

Candidate compounds for new thermoelectric and superconducting materials, which have narrow band gap and flat bands near band edges, were exhaustively searched by the high-throughput first-principles calculation from an inorganic materials database named AtomWork. We focused on PbBiTe which has the similar electronic band structure and the same crystal structure with those of a pressure-induced superconductor SnBiSe explored by the same data-driven approach. The PbBiTe was successfully synthesized as single crystals using a melt and slow cooling method.

Ionic-liquid-gating setup for stable measurements and reduced electronic inhomogeneity at low temperatures.

The ionic-liquid-gating technique can be applied to the search for novel physical phenomena at low temperatures because of its wide controllability of the charge carrier density. Ionic-liquid-gated field-effect transistors are often fragile upon cooling, however, because of the large difference between the thermal expansion coefficients of frozen ionic liquids and solid target materials. In this paper, we provide a practical technique for setting up ionic-liquid-gated field-effect transistors for low-temperature measurements.

Superconductivity in alkali-doped fullerene nanowhiskers.

Superconductivity in alkali metal-doped fullerene nanowhiskers (C60NWs) was observed in K3.3C60NWs, Rb3.0C60NWs and Cs2.

Glucose-induced abnormal egg-laying rate in Caenorhabditis elegans.

High glucose reduced the egg-laying rate of the nematode Caenorhabditis elegans and was dependent on serotonergic signaling. Antidiabetic drugs of the biguanide and thiazolidine classes ameliorated the detrimental effect of glucose on egg-laying rate, suggesting the possibility that this quick and easy assay system may be applicable to whole-animal screening for novel antidiabetic drugs, at least, of these classes.

Probing the electronic properties of ternary A MB ( = 1: A = Ca, Sr; M = Rh, Ir and = 3: A = Ca, Sr; M = Rh) phases: observation of superconductivity.

We follow the evolution of the electronic properties of the titled homologous series when as well as the atomic type of A and M are varied where for = 1, A = Ca, Sr and M = Rh, Ir while for = 3, A = Ca, Sr and M = Rh. The crystal structure of = 1 members is known to be CaRhB-type (), while that of = 3 is CaRhB-type (); the latter can be visualized as a stacking of structural fragments from AMB (6/) and AMB. The metallic properties of the = 1 and 3 members are distinctly different: on the one hand, the = 1 members are characterized by a linear coefficient of the electronic specific heat ≈ 3 mJ mol K, a Debye temperature ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe.

An induced pluripotent stem cell-mediated and integration-free factor VIII expression system.

Human artificial chromosome (HAC) has several advantages as a gene therapy vector, including stable episomal maintenance and the ability to carry large gene inserts. Induced pluripotent stem (iPS) cells also have a great potential for gene therapy, which can be generated from an individual's own tissues and contribute to any tissues when reintroduced. A Sendai virus (SeV) vector with reprogramming factors is a powerful tool for generating iPS cells because of the high infection efficiency without the risk of integration into host chromosomes.

Regulation of autophagy and its associated cell death by "sphingolipid rheostat": reciprocal role of ceramide and sphingosine 1-phosphate in the mammalian target of rapamycin pathway.

The role of "sphingolipid rheostat" by ceramide and sphingosine 1-phosphate (S1P) in the regulation of autophagy remains unclear. In human leukemia HL-60 cells, amino acid deprivation (AA(-)) caused autophagy with an increase in acid sphingomyleinase (SMase) activity and ceramide, which serves as an autophagy inducing lipid. Knockdown of acid SMase significantly suppressed the autophagy induction.

Regulation of cell migration by sphingomyelin synthases: sphingomyelin in lipid rafts decreases responsiveness to signaling by the CXCL12/CXCR4 pathway.

Sphingomyelin synthase (SMS) catalyzes the formation of sphingomyelin, a major component of the plasma membrane and lipid rafts. To investigate the role of SMS in cell signaling and migration induced by binding of the chemokine CXCL12 to CXCR4, we used mouse embryonic fibroblasts deficient in SMS1 and/or SMS2 and examined the effects of SMS deficiency on cell migration. SMS deficiency promoted cell migration through a CXCL12/CXCR4-dependent signaling pathway involving extracellular signal-regulated kinase (ERK) activation.

Superconducting fullerene nanowhiskers.

We synthesized superconducting fullerene nanowhiskers (C(60)NWs) by potassium (K) intercalation. They showed large superconducting volume fractions, as high as 80%. The superconducting transition temperature at 17 K was independent of the K content (x) in the range between 1.

Sphingomyelin synthase 1-generated sphingomyelin plays an important role in transferrin trafficking and cell proliferation.

Transferrin (Tf) endocytosis and recycling are essential for iron uptake and the regulation of cell proliferation. Tf and Tf receptor (TfR) complexes are internalized via clathrin-coated pits composed of a variety of proteins and lipids and pass through early endosomes to recycling endosomes. We investigated the role of sphingomyelin (SM) synthases (SMS1 and SMS2) in clathrin-dependent trafficking of Tf and cell proliferation.

Integration-free and stable expression of FVIII using a human artificial chromosome.

Human artificial chromosome (HAC) has several advantages as a gene therapy vector, including stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts. To examine the copy number effect on the gene expression levels and its stability for a long-term culture for a future application in gene therapy, we constructed a HAC vector carrying the human factor VIII (FVIII) complementary DNA, FVIII-HAC in Chinese hamster ovary (CHO) cells. One and more copies of FVIII gene on the HAC were expressed in the copy-number-dependent manner in the CHO cells.

Snake venom metalloproteinases: structure, function and relevance to the mammalian ADAM/ADAMTS family proteins.

Metalloproteinases are among the most abundant toxins in many Viperidae venoms. Snake venom metalloproteinases (SVMPs) are the primary factors responsible for hemorrhage and may also interfere with the hemostatic system, thus facilitating loss of blood from the vasculature of the prey. SVMPs are phylogenetically most closely related to mammalian ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin type-1 motif) family of proteins and, together with them, constitute the M12B clan of metalloendopeptidases.

Effect of dibutyryl cyclic adenosine monophosphate on the gene expression of plasminogen activator inhibitor-1 and tissue factor in adipocytes.

Introduction: Hypertrophic adipocytes in obese states express the elevated levels of plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF). An increase in the intracellular concentration of cyclic adenosine monophosphate (cAMP) promotes triglyceride hydrolysis and may improve dysregulation of adipocyte metabolism. Here, we investigate the effect of dibutyryl-cAMP (a phosphodiesterase-resistant analog of cAMP) on the gene expression of PAI-1 and TF in adipocytes.

Self-interaction of soluble and surface-bound beta2-glycoprotein I and its enhancement by lupus anticoagulants.

Antiphospholipid antibodies found in antiphospholipid syndrome are autoantibodies to phospholipid-binding proteins, such as beta2-glycoprotein I (beta2GPI). We have previously reported that among these antibodies, the so-called lupus anticoagulants (LAs) augment beta2GPI binding to the phospholipid membrane surface, which is associated with the pathological action of LAs. However, the molecular mechanisms underlying this augmentation are uncertain.

Intratracheal gene transfer of tissue factor pathway inhibitor attenuates pulmonary fibrosis.

Activation of the coagulation system and increased expression of tissue factor (TF) in pulmonary fibrosis associated with acute and chronic lung injury have been previously documented. In the present study, we evaluated the effect of TF inhibition with intratracheal gene transfer of tissue factor pathway inhibitor (TFPI), a potent and highly specific endogenous inhibitor of TF-dependent coagulation activation, in a rat model of bleomycin-induced lung fibrosis. Significant lung fibrotic changes as assessed by histologic findings and hydroxyproline content, and increased procoagulant activity and thrombin generation in bronchoalveolar lavage fluid were detected in rats after intratracheal injection of bleomycin.

['Vegetable wasps and plant worms' and G-protein-coupled receptors].

Following the discovery of an immunosuppressive substance isolated from one of the entomopathogenic fungi 'vegetable wasps and plant worms', FTY720, whose immunosuppressive action is more potent than that of cyclosporin, was developed. In contrast to classical immunosuppressants such as cyclosporin, FTY720 does not affect the growth, maturation and activation of lymphocytes, but causes a reduction in the number of circulating lymphocytes as a result of enhanced homing of lymphocytes to the secondary lymphoid organs. It has recently been reported that FTY720 is phosphorylated in vivo by sphingosine kinase, and the phosphorylated FTY720 is a ligand of the receptors of sphingosine 1-phosphate (S1P), which are G-protein-coupled receptors.

Synergistic effect of sphingosine 1-phosphate on thrombin-induced tissue factor expression in endothelial cells.

Sphingosine 1-phosphate (S1P), a bioactive lipid, is produced and stored in platelets and is released from activated platelets during blood coagulation activation. Thrombin, which is also generated during blood coagulation, has been shown to induce tissue factor (TF), the initiator of blood coagulation, in endothelial cells (ECs); however, the effect of S1P on this process is not evaluated. Here we demonstrated that S1P strongly potentiated thrombin-induced TF expression in ECs and that S1P itself did not induce TF expression.