Showing papers by "Kumamoto University published in 2008"
TL;DR: It is proposed that cohesin functions as a transcriptional insulator, and it is speculated that subtle deficiencies in this function contribute to ‘cohesinopathies’ such as Cornelia de Lange syndrome.
Abstract: Cohesin complexes mediate sister-chromatid cohesion in dividing cells but may also contribute to gene regulation in postmitotic cells. How cohesin regulates gene expression is not known. Here we describe cohesin-binding sites in the human genome and show that most of these are associated with the CCCTC-binding factor (CTCF), a zinc-finger protein required for transcriptional insulation. CTCF is dispensable for cohesin loading onto DNA, but is needed to enrich cohesin at specific binding sites. Cohesin enables CTCF to insulate promoters from distant enhancers and controls transcription at the H19/IGF2 (insulin-like growth factor 2) locus. This role of cohesin seems to be independent of its role in cohesion. We propose that cohesin functions as a transcriptional insulator, and speculate that subtle deficiencies in this function contribute to 'cohesinopathies' such as Cornelia de Lange syndrome.
1,164 citations
TL;DR: In this study of patients with type 2 diabetes, low-dose aspirin as primary prevention did not reduce the risk of cardiovascular events.
Abstract: Context Previous trials have investigated the effects of low-dose aspirin on primary prevention of cardiovascular events, but not in patients with type 2 diabetes. Objective To examine the efficacy of low-dose aspirin for the primary prevention of atherosclerotic events in patients with type 2 diabetes. Design, Setting, and Participants Multicenter, prospective, randomized, open-label, blinded, end-point trial conducted from December 2002 through April 2008 at 163 institutions throughout Japan, which enrolled 2539 patients with type 2 diabetes without a history of atherosclerotic disease and had a median follow-up of 4.37 years. Interventions Patients were assigned to the low-dose aspirin group (81 or 100 mg per day) or the nonaspirin group. Main Outcome Measures Primary end points were atherosclerotic events, including fatal or nonfatal ischemic heart disease, fatal or nonfatal stroke, and peripheral arterial disease. Secondary end points included each primary end point and combinations of primary end points as well as death from any cause. Results A total of 154 atherosclerotic events occurred: 68 in the aspirin group (13.6 per 1000 person-years) and 86 in the nonaspirin group (17.0 per 1000 person-years) (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.58-1.10; log-rank test, P = .16). The combined end point of fatal coronary events and fatal cerebrovascular events occurred in 1 patient (stroke) in the aspirin group and 10 patients (5 fatal myocardial infarctions and 5 fatal strokes) in the nonaspirin group (HR, 0.10; 95% CI, 0.01-0.79; P = .0037). A total of 34 patients in the aspirin group and 38 patients in the nonaspirin group died from any cause (HR, 0.90; 95% CI, 0.57-1.14; log-rank test, P = .67). The composite of hemorrhagic stroke and significant gastrointestinal bleeding was not significantly different between the aspirin and nonaspirin groups. Conclusion In this study of patients with type 2 diabetes, low-dose aspirin as primary prevention did not reduce the risk of cardiovascular events. Trial Registration clinicaltrials.gov Identifier: NCT00110448Published online November 9, 2008 (doi: 10.1001/jama.2008.623).
701 citations
TL;DR: It is suggested that tumour‐derived M‐CSF induces a shift of microglia/macrophages towards the M2 phenotype, which influences tumour growth.
Abstract: Within tumours, many non-neoplastic cells such as fibroblasts, endothelial cells, and macrophages assist tumour growth by producing various growth factors and pro-angiogenic cytokines. Various tumour-derived molecules drive tumour-associated macrophages towards an anti-inflammatory phenotype (M2) and thus promoting tumour growth. Here we investigated microglia/macrophage differentiation in glioma tissues by means of immunostaining of paraffin-embedded glioma samples. The number of microglia/macrophages with positive staining for CD163 and CD204, which are believed to be markers for M2 macrophages, was correlated with the histological grade of the gliomas. The ratio of M2 macrophages in the tumour-associated microglia/macrophages was also associated with the histological grade. Culture supernatant from the glioma cell line can stimulate macrophages to develop into the M2 phenotype in vitro. Macrophage colony-stimulating factor (M-CSF), which strongly induces M2 polarization of macrophages, was significantly correlated with histological malignancy and with the proportion of M2 microglia/macrophages in vivo. In addition, the proportion of M2 microglia/macrophages and M-CSF expression in tumour cells correlated well with proliferation of glioblastoma cells. These results suggest that tumour-derived M-CSF induces a shift of microglia/macrophages towards the M2 phenotype, which influences tumour growth. Evaluation of the proportion of M2 microglia/macrophages and M-CSF expression in tumour tissue would be useful for assessment of microglia/macrophage proliferative activity and the prognosis of patients with gliomas.
657 citations
TL;DR: The results show that distinct subpopulations of macrophages can promote muscle injury or repair in muscular dystrophy, and that therapeutic interventions that affect the balance between M1 and M2 macrophage populations may influence the course of muscular Dystrophy.
Abstract: Duchenne muscular dystrophy (DMD) is the most common, lethal, muscle-wasting disease of childhood. Previous investigations have shown that muscle macrophages may play an important role in promoting the pathology in the mdx mouse model of DMD. In the present study, we investigate the mechanism through which macrophages promote mdx dystrophy and assess whether the phenotype of the macrophages changes between the stage of peak muscle necrosis (4 weeks of age) and muscle regeneration (12 weeks). We find that 4-week-old mdx muscles contain a population of pro-inflammatory, classically activated M1 macrophages that lyse muscle in vitro by NO-mediated mechanisms. Genetic ablation of the iNOS gene in mdx mice also significantly reduces muscle membrane lysis in 4-week-old mdx mice in vivo. However, 4-week mdx muscles also contain a population of alternatively activated, M2a macrophages that express arginase. In vitro assays show that M2a macrophages reduce lysis of muscle cells by M1 macrophages through the competition of arginase in M2a cells with iNOS in M1 cells for their common, enzymatic substrate, arginine. During the transition from the acute peak of mdx pathology to the regenerative stage, expression of IL-4 and IL-10 increases, either of which can deactivate the M1 phenotype and promote activation of a CD163+, M2c phenotype that can increase tissue repair. Our findings further show that IL-10 stimulation of macrophages activates their ability to promote satellite cell proliferation. Deactivation of the M1 phenotype is also associated with a reduced expression of iNOS, IL-6, MCP-1 and IP-10. Thus, these results show that distinct subpopulations of macrophages can promote muscle injury or repair in muscular dystrophy, and that therapeutic interventions that affect the balance between M1 and M2 macrophage populations may influence the course of muscular dystrophy.
465 citations
TL;DR: It is suggested that galectin-9 ameliorates CIA by suppressing the generation of Th17, promoting the induction of regulatory T cells, and it suppresses differentiation to Th17 cells in vitro.
419 citations
TL;DR: Several lines of evidence reveal differential roles of Angptl structural domains in both angiogenesis and metabolism, and what is currently known about Angptls function is reviewed.
315 citations
TL;DR: It is reported that a sugar transport facilitator family member protein GLUT9 (SLC2A9) functions as an efflux transporter of urate from the tubular cell and is proposed to be renamed URATv1 (voltage-driven urate transporter 1).
308 citations
TL;DR: The results suggested that SW could effectively be used to hydrolyze deoiled rice bran to produce useful protein and amino acids and was shown to be suitable for use as culture medium for yeast growth.
297 citations
TL;DR: In this paper, the authors have demonstrated the reasons why CeO2 becomes an active catalyst for diesel particulate (soot) abatement, which attracts recent worldwide attention in the development of clean diesel automobiles.
Abstract: The present work has demonstrated the reasons why CeO2 becomes an active catalyst for diesel particulate (soot) abatement, which attracts recent worldwide attention in the development of clean diesel automobiles. Four typical fluorite-type oxides, CeO2, ZrO2, Pr6O11, and a CeO2−ZrO2 solid solution have been studied as model catalysts for soot oxidation in conjunction with the redox property and the reactivity of solid oxygen species. It was found that the redox property measured in terms of oxygen storage/release capacity was not the sole determining factor for the observed catalytic activity decreasing in the order of CeO2 ≫ Pr6O11 ≈ CeO2−ZrO2 > ZrO2. The reactivity of oxygen species involved in the redox cycles would rather be important. The ESR measurement showed that admission of O2 to the pre-reduced CeO2 surface generated superoxide ions (O2−). Such reactive oxygen species were less abundant on CeO2−ZrO2 and were not detected on ZrO2 and Pr6O11. The labeled and unlabeled O2 pulse experiments demonst...
287 citations
TL;DR: In this article, the degradation of lignin was studied in near and supercritical water at temperatures 623 and 673 K using a batch type reactor, where the effects of temperature and reaction time were combined into a single severity parameter that was used to monitor the degradation.
Abstract: Lignin as a part of wood biomass has been proposed to be an alternative source of chemical compounds for industrial applications. The degradation of lignin was studied in near and supercritical water at temperatures 623 and 673 K using a batch type reactor. The effects of temperature and reaction time were combined into a single severity parameter that was used to monitor the degradation of lignin to liquid fraction. With an increase in the reaction time at the same conditions, higher molecular weight fractions decreased and the amount of lower molecular weight fractions increased. The chemical species in liquid products and solid residues (char) were analyzed using high performance liquid chromatography with a Jasco MD-2010 Plus and Fourier transform infrared spectrophotometer, respectively. The main products in methanol soluble fraction were catechol (28.37 wt%), phenol (7.53 wt%), m,p-cresol (7.87 wt%) and o-cresol (3.80 wt%). Based on the experimental results, a reaction mechanism for the degradation of lignin was proposed. Next, optimum-operating conditions for high yields of valuable chemicals could be explored.
285 citations
TL;DR: The present line of research focuses on the presumption that an inhibitor that can maximize interactions in the HIV-1 protease active site, particularly with the enzyme backbone atoms, will likely retain these interactions with mutant enzymes.
Abstract: The discovery of human immunodeficiency virus (HIV) protease inhibitors (PIs) and their utilization in highly active antiretroviral therapy (HAART) have been a major turning point in the management of HIV/acquired immune-deficiency syndrome (AIDS). However, despite the successes in disease management and the decrease of HIV/AIDS-related mortality, several drawbacks continue to hamper first-generation protease inhibitor therapies. The rapid emergence of drug resistance has become the most urgent concern because it renders current treatments ineffective and therefore compels the scientific community to continue efforts in the design of inhibitors that can efficiently combat drug resistance. The present line of research focuses on the presumption that an inhibitor that can maximize interactions in the HIV-1 protease active site, particularly with the enzyme backbone atoms, will likely retain these interactions with mutant enzymes. Our structure-based design of HIV PIs specifically targeting the protein backbone has led to exceedingly potent inhibitors with superb resistance profiles. We initially introduced new structural templates, particulary nonpeptidic conformationally constrained P 2 ligands that would efficiently mimic peptide binding in the S 2 subsite of the protease and provide enhanced bioavailability to the inhibitor. Cyclic ether derived ligands appeared as privileged structural features and allowed us to obtain a series of potent PIs. Following our structure-based design approach, we developed a high-affinity 3( R),3a( R),6a( R)-bis-tetrahydrofuranylurethane (bis-THF) ligand that maximizes hydrogen bonding and hyrophobic interactions in the protease S 2 subsite. Combination of this ligand with a range of different isosteres led to a series of exceedingly potent inhibitors. Darunavir, initially TMC-114, which combines the bis-THF ligand with a sulfonamide isostere, directly resulted from this line of research. This inhibitor displayed unprecedented enzyme inhibitory potency ( K i = 16 pM) and antiviral activity (IC 90 = 4.1 nM). Most importantly, it consistently retained is potency against highly drug-resistant HIV strains. Darunavir's IC 50 remained in the low nanomolar range against highly mutated HIV strains that displayed resistance to most available PIs. Our detailed crystal structure analyses of darunavir-bound protease complexes clearly demonstrated extensive hydrogen bonding between the inhibitor and the protease backbone. Most strikingly, these analyses provided ample evidence of the unique contribution of the bis-THF as a P 2-ligand. With numerous hydrogen bonds, bis-THF was shown to closely and tightly bind to the backbone atoms of the S 2 subsite of the protease. Such tight interactions were consistently observed with mutant proteases and might therefore account for the unusually high resistance profile of darunavir. Optimization attempts of the backbone binding in other subsites of the enzyme, through rational modifications of the isostere or tailor made P 2 ligands, led to equally impressive inhibitors with excellent resistance profiles. The concept of targeting the protein backbone in current structure-based drug design may offer a reliable strategy for combating drug resistance.
TL;DR: A weak-base anion exchange fiber named FVA with primary amino groups for selective and rapid removal of arsenate species was prepared by means of electron irradiation induced liquid phase graft polymerization of N-vinylformamide onto polyethylene coated polypropylene fibers and by the subsequent alkaline hydrolysis of amide group on the grafted polymer chains.
TL;DR: This work shows that Wnt5a and its receptor Ror2 are expressed in a graded manner along the AP axis of the palate, and reveals distinct regulatory roles for Wnt 5a in gene expression and cell proliferation and an essential role in the regulation of directional cell migration within the developing palate.
Abstract: Tissue and molecular heterogeneities are present in the developing
secondary palate along the anteroposterior (AP) axis in mice. Here, we show
that Wnt5a and its receptor Ror2 are expressed in a graded manner along the AP
axis of the palate. Wnt5a deficiency leads to a complete cleft of the
secondary palate, which exhibits distinct phenotypic alterations at
histological, cellular and molecular levels in the anterior and posterior
regions of the palate. We demonstrate that there is directional cell migration
within the developing palate. In the absence of Wnt5a, this
directional cell migration does not occur. Genetic studies and in vitro organ
culture assays further demonstrate a role for Ror2 in mediating Wnt5a
signaling in the regulation of cell proliferation and migration during palate
development. Our results reveal distinct regulatory roles for Wnt5a in gene
expression and cell proliferation along the AP axis of the developing palate,
and an essential role for Wnt5a in the regulation of directional cell
migration.
TL;DR: The coincidence of the excitation spectrum and the band gap absorbance indicates that the visible emission results from energy transfer within the nanosheet, which is a result of a two-step energy transfer cascade within the Nanosheet from the Ti-O network to Gd(3+) and then to Eu(3+).
Abstract: Luminescent perovskite nanosheets were prepared by exfoliation of single- or double- layered perovskite oxides, K2Ln2Ti3O10, KLnNb2O7, and RbLnTa2O7 (Ln: lanthanide ion) The thickness of the individual nanosheets corresponded to those of the perovskite block in the parent layered compounds Intense red and green emissions were observed in aqueous solutions with Gd14Eu06Ti3O10- and La07Tb03Ta2O7-nanosheets, respectively, under UV illumination with energies greater than the corresponding host oxide band gap The coincidence of the excitation spectrum and the band gap absorbance indicates that the visible emission results from energy transfer within the nanosheet The red emission intensity of the Gd14Eu06Ti3O10-nanosheets was much stronger than that of the La090Eu005Nb2O7-nanosheets reported previously The strong emission intensity is a result of a two-step energy transfer cascade within the nanosheet from the Ti−O network to Gd3+ and then to Eu3+ The emission intensities of the Gd14Eu06Ti3O10-
TL;DR: The nickel hydroxide nanosheets exhibited charge-discharge properties in strong alkaline electrolyte and the morphology of the nanosheet changed during the electrochemical reaction.
Abstract: One-nanometer-thick nickel hydroxide nanosheets were prepared by exfoliation of layered nickel hydroxides intercalated with dodecyl sulfate (DS) ions. The shape of the nanosheets was hexagonal, as was that of the layered nickel hydroxides intercalated with DS ions. The nickel hydroxide nanosheets exhibited charge-discharge properties in strong alkaline electrolyte. The morphology of the nanosheet changed during the electrochemical reaction.
TL;DR: It is found that cytoplasmic vacuoles induced in pancreatic acinar cells by experimental pancreatitis were autophagic in origin, as demonstrated by microtubule-associated protein 1 light chain 3 expression and electron microscopy experiments, and trypsinogen activation was greatly reduced in the absence of autophagy.
Abstract: Autophagy is mostly a nonselective bulk degradation system within cells. Recent reports indicate that autophagy can act both as a protector and killer of the cell depending on the stage of the disease or the surrounding cellular environment (for review see Cuervo, A.M. 2004. Trends Cell Biol. 14:70-77). We found that cytoplasmic vacuoles induced in pancreatic acinar cells by experimental pancreatitis were autophagic in origin, as demonstrated by microtubule-associated protein 1 light chain 3 expression and electron microscopy experiments. To analyze the role of macroautophagy in acute pancreatitis, we produced conditional knockout mice lacking the autophagy-related 5 gene in acinar cells. Acute pancreatitis was not observed, except for very mild edema in a restricted area, in conditional knockout mice. Unexpectedly, trypsinogen activation was greatly reduced in the absence of autophagy. These results suggest that autophagy exerts devastating effects in pancreatic acinar cells by activation of trypsinogen to trypsin in the early stage of acute pancreatitis through delivering trypsinogen to the lysosome.
TL;DR: A checklist of the 870 current valid species of squat lobsters of the world (families Chirostylidae, Galatheidae and Kiwaidae) is presented and includes the complete taxonomic synonymy and geographical distribution of each species.
Abstract: Taxonomic and ecological interest in squat lobsters has grown considerably over the last two decades. A checklist of the 870 current valid species of squat lobsters of the world (families Chirostylidae, Galatheidae and Kiwaidae) is presented. The compilation includes the complete taxonomic synonymy and geographical distribution of each species plus type information (type locality, repository and registration number). The numbers of described species in the world’s major ocean basins are summarised.
TL;DR: Partial nitritation using inhibition of free ammonia and free nitric acid is an effective technique for the treatment of high concentrations of ammonium in wastewaters and the stability of its long-term operation was investigated.
TL;DR: Data suggested that AOPPs might be new ligands of endothelial RAGE, which activates vascular ECs via RAGE-mediated signals.
Abstract: The accumulation of advanced oxidation protein products (AOPPs) has been linked to vascular lesions in diabetes, chronic renal insufficiency, and atherosclerosis. However, the signaling pathway involved in AOPPs-induced endothelial cells (ECs) perturbation is unknown and was investigated. AOPPs modified human serum albumin (AOPPs-HSA) bound to the receptor for advanced glycation end products (RAGE) in a dose-dependent and saturable manner. AOPPs-HSA competitively inhibited the binding of soluble RAGE (sRAGE) with its preferential ligands advanced glycation end products (AGEs). Incubation of AOPPs, either prepared in vitro or isolated from uremic serum, with human umbilical vein ECs induced superoxide generation, activation of NAD(P)H oxidase, ERK 1/2 and p38, and nuclear translocation of NF-kappaB. Activation of signaling pathway by AOPPs-ECs interaction resulted in overexpression of VCAM-1 and ICAM-1 at both gene and protein levels. This AOPPs-triggered biochemical cascade in ECs was prevented by blocking RAGE with either anti-RAGE IgG or excess sRAGE, but was not affected by the neutralizing anti-AGEs IgG. These data suggested that AOPPs might be new ligands of endothelial RAGE. AOPPs-HSA activates vascular ECs via RAGE-mediated signals.
TL;DR: The clinical result of S BRT for oligometastatic lung tumors in the institute was comparable to that after surgical metastasectomy; thus, SBRT could be an effective treatment of pulmonary oligometastsases.
Abstract: Purpose Since 1998, we have treated primary and oligometastatic lung tumors with stereotactic body radiotherapy (SBRT). The term "oligometastasis" is used to indicate a small number of metastases limited to an organ. We evaluated our clinical experience of SBRT for oligometastatic lung tumors. Methods and Materials A total of 34 patients with oligometastatic lung tumors were included in this study. The primary involved organs were the lung ( n = 15), colorectum ( n = 9), head and neck ( n = 5), kidney ( n = 3), breast ( n = 1), and bone ( n = 1). Five to seven, noncoplanar, static 6-MV photon beams were used to deliver 48 Gy ( n = 18) or 60 Gy ( n = 16) at the isocenter, with 12 Gy/fraction within 4–18 days (median, 12 days). Results The overall survival rate, local relapse-free rate, and progression-free rate at 2 years was 84.3%, 90.0%, and 34.8%, respectively. No local progression was observed in tumors irradiated with 60 Gy. SBRT-related pulmonary toxicities were observed in 4 (12%) Grade 2 cases and 1 (3%) Grade 3 case. Patients with a longer disease-free interval had a greater overall survival rate. Conclusion The clinical result of SBRT for oligometastatic lung tumors in our institute was comparable to that after surgical metastasectomy; thus, SBRT could be an effective treatment of pulmonary oligometastases.
TL;DR: The GSK3β/β-catenin signaling axis regulated by FGF and Wnt signals plays a pivotal role in the maintenance of neural stem/precursor cells by linking the cell proliferation to the inhibition of differentiation.
Abstract: The proliferation and differentiation of neural precursor cells are mutually exclusive during brain development. Despite its importance for precursor cell self renewal, the molecular linkage between these two events has remained unclear. Fibroblast growth factor 2 (FGF2) promotes neural precursor cell proliferation and concurrently inhibits their differentiation, suggesting a cross talk between proliferation and differentiation signaling pathways downstream of the FGF receptor. We demonstrate that FGF2 signaling through phosphatidylinositol 3 kinase activation inactivates glycogen synthase kinase 3beta (GSK3beta) and leads to the accumulation of beta-catenin in a manner different from that in the Wnt canonical pathway. The nuclear accumulated beta-catenin leads to cell proliferation by activating LEF/TCF transcription factors and concurrently inhibits neuronal differentiation by potentiating the Notch1-RBP-Jkappa signaling pathway. beta-Catenin and the Notch1 intracellular domain form a molecular complex with the promoter region of the antineurogenic hes1 gene, allowing its expression. This signaling interplay is especially essential for neural stem cell maintenance, since the misexpression of dominant-active GSK3beta completely inhibits the self renewal of neurosphere-forming stem cells and prompts their neuronal differentiation. Thus, the GSK3beta/beta-catenin signaling axis regulated by FGF and Wnt signals plays a pivotal role in the maintenance of neural stem/precursor cells by linking the cell proliferation to the inhibition of differentiation.
TL;DR: Soybean oil and olive oil were investigated as continuous co-solvents for supercritical carbon dioxide (SC-CO(2) extraction of astaxanthin from Haematococcus pluvialis and the extraction efficiency was enhanced, with the most appropriate level of soybean oil in the solvent mixture being 10% by volume.
TL;DR: The common SLCO1B3 GG/AA haplotype is associated with impaired testosterone transport and improved survival in patients with prostatic cancer.
Abstract: Purpose: The organic anion transporter OATP1B3, encoded by SLCO1B3, is involved in the transport of steroid hormones. However, its role in testosterone uptake and clinical outcome of prostatic cancer is unknown. This study examined (a) the SLCO1B3 genotype in cancer cells as well as the uptake of testosterone by cells transfected with genetic variants of SLCO1B3; (b) the expression of OATP1B3 in normal prostate, benign prostatic hyperplasia, and prostatic cancer; and (c) the role of SLCO1B3 haplotype on clinical outcome of Caucasian patients with androgen-independent prostatic cancer. Experimental Design:SLCO1B3 genotype was assessed in the NCI-60 panel of tumor cells by sequencing, whereas testosterone transport was analyzed in Cos-7 cells transfected with WT, 334G, and 699A SLCO1B3 variants. OATP1B3 expression in prostatic tissues was examined by fluorescence microscopy, and the relationship between SLCO1B3 haplotypes and survival was examined in patients. Results: Cells transfected with wild-type (334T/699G) SLCO1B3, or with a vector containing either the 334G or 699A variants, actively transported testosterone, whereas its uptake was impaired in cells transfected with a gene carrying both 334G and 699A single nucleotide polymorphisms. Prostatic cancer overexpresses OATP1B3 compared with normal or benign hyperplastic tissue; patients with SLCO1B3 334GG/699AA haplotype showed longer median survival (8.5 versus 6.4 years; P = 0.020) and improved survival probability at 10 years (42% versus 23%; P Conclusions: The common SLCO1B3 GG/AA haplotype is associated with impaired testosterone transport and improved survival in patients with prostatic cancer.
TL;DR: DWI may be able to be used in place of FDG-PET to distinguish malignant from benign pulmonary nodules/masses with fewer false-positive results compared with FDg-PET.
TL;DR: In this article, low energy ion measurements on the lunar orbit are realized more than 30 years after the Apollo period by low energy charged particle analyzers MAP-PACE on board SELENE(KAGUYA), which have found that 0.1%∼1% of the solar wind protons are reflected back from the Moon instead of being absorbed by the lunar surface.
Abstract: [1] Interaction between the solar wind and objects in the solar system varies largely according to the settings, such as the existence of a global intrinsic magnetic field and/or thick atmosphere. The Moon's case is characterized by the absence of both of them. Low energy ion measurements on the lunar orbit is realized more than 30 years after the Apollo period by low energy charged particle analyzers MAP-PACE on board SELENE(KAGUYA). MAP-PACE ion sensors have found that 0.1%∼1% of the solar wind protons are reflected back from the Moon instead of being absorbed by the lunar surface. Some of the reflected ions are accelerated above solar wind energy as they are picked-up by the solar wind convection electric field. The proton reflection that we have newly discovered around the Moon should be a universal process that characterizes the environment of an airless body.
TL;DR: Induction of 4E-BP1 induction contributes to the maintenance of beta cell homeostasis during ER stress and is a potential therapeutic target for diabetes.
TL;DR: It is demonstrated that inactivation of Fbxw7 in hematopoietic cells causes premature depletion of HSCs due to active cell cycling and p53-dependent apoptosis, and functions as a fail-safe mechanism against both premature HSC loss and leukemogenesis.
Abstract: Common molecular machineries between hematopoietic stem cell (HSC) maintenance and leukemia prevention have been highlighted. The tumor suppressor Fbxw7 (F-box and WD-40 domain protein 7), a subunit of an SCF-type ubiquitin ligase complex, induces the degradation of positive regulators of the cell cycle. We demonstrate that inactivation of Fbxw7 in hematopoietic cells causes premature depletion of HSCs due to active cell cycling and p53-dependent apoptosis. Interestingly, Fbxw7 deletion also confers a selective advantage to cells with suppressed p53 function, eventually leading to development of T-cell acute lymphoblastic leukemia (T-ALL). Thus, Fbxw7 functions as a fail-safe mechanism against both premature HSC loss and leukemogenesis.
TL;DR: Sensory evaluation of milk added with the hydrolysis product of deoiled rice bran indicated the potential use of the product as a nutritious drink and it was found to have antioxidant activity as tested by ABTS(.)(+) scavenging assay.
TL;DR: Phylogenetic analysis and genome organization of the chemokine genes showed that successive tandem duplication events generated the CX genes from the CC subfamily, which was generated in zebrafish.
Abstract: The chemokine family plays important roles in cell migration and activation. In humans, at least 44 members are known. Based on the arrangement of the four conserved cysteine residues, chemokines are now classified into four subfamilies, CXC, CC, XC and CX3C. Given that zebrafish is an important experimental model and teleost fishes constitute an evolutionarily diverse group that forms half the vertebrate species, it would be useful to compare the zebrafish chemokine system with those of mammals. Prior to this study, however, only incomplete lists of the zebrafish chemokine genes were reported. We systematically searched chemokine genes in the zebrafish genome and EST databases, and identified more than 100 chemokine genes. These genes were CXC, CC and XC subfamily members, while no CX3C gene was identified. We also searched chemokine genes in pufferfish fugu and Tetraodon, and found only 18 chemokine genes in each species. The majority of the identified chemokine genes are unique to zebrafish or teleost fishes. However, several groups of chemokines are moderately similar to human chemokines, and some chemokines are orthologous to human homeostatic chemokines CXCL12 and CXCL14. Zebrafish also possesses a novel species-specific subfamily consisting of five members, which we term the CX subfamily. The CX chemokines lack one of the two N-terminus conserved cysteine residues but retain the third and the fourth ones. (Note that the XC subfamily only retains the second and fourth of the signature cysteines residues.) Phylogenetic analysis and genome organization of the chemokine genes showed that successive tandem duplication events generated the CX genes from the CC subfamily. Recombinant CXL-chr24a, one of the CX subfamily members on chromosome 24, showed marked chemotactic activity for carp leukocytes. The mRNA was expressed mainly during a certain period of the embryogenesis, suggesting its role in the zebrafish development. The phylogenic and genomic organization analyses suggest that a substantial number of chemokine genes in zebrafish were generated by zebrafish-specific tandem duplication events. During such duplications, a novel chemokine subfamily termed CX was generated in zebrafish. Only two human chemokines CXCL12 and CXCL14 have the orthologous chemokines in zebrafish. The diversification observed in the numbers and sequences of chemokines in the fish may reflect the adaptation of the individual species to their respective biological environment.
TL;DR: It is demonstrated that other TLR signaling (TLR2, 3, 4, 7, and 9) is also suppressed by M UC1/Muc1, suggesting that MUC1/ Muc1 may play a crucial role during airway infection and inflammation by various pathogenic bacteria and viruses.
Abstract: MUC1 (MUC1 in humans and Muc1 in nonhuman species) is a transmembrane mucin-like glycoprotein expressed in epithelial cells lining various mucosal surfaces as well as hematopoietic cells. Recently, we showed that Muc1−/− mice exhibited greater inflammatory responses to Pseudomonas aeruginosa or its flagellin compared with their wild-type littermates, and our studies with cultured cells revealed that MUC1/Muc1 suppressed the Toll-like receptor (TLR) 5 signaling pathway, suggesting its anti-inflammatory role. Here we demonstrate that other TLR signaling (TLR2, 3, 4, 7, and 9) is also suppressed by MUC1/Muc1. The results from this study suggest that MUC1/Muc1 may play a crucial role during airway infection and inflammation by various pathogenic bacteria and viruses.