Showing papers by "Hokkaido University published in 2008"

The Physcomitrella Genome Reveals Evolutionary Insights into the Conquest of Land by Plants

Abstract: We report the draft genome sequence of the model moss Physcomitrella patens and compare its features with those of flowering plants, from which it is separated by more than 400 million years, and unicellular aquatic algae. This comparison reveals genomic changes concomitant with the evolutionary movement to land, including a general increase in gene family complexity; loss of genes associated with aquatic environments (e.g., flagellar arms); acquisition of genes for tolerating terrestrial stresses (e.g., variation in temperature and water availability); and the development of the auxin and abscisic acid signaling pathways for coordinating multicellular growth and dehydration response. The Physcomitrella genome provides a resource for phylogenetic inferences about gene function and for experimental analysis of plant processes through this plant's unique facility for reverse genetics.

Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type

Abstract: Mesenchymal stem cells (MSCs) can differentiate not only into mesenchymal lineage cells but also into various other cell lineages. As MSCs can easily be isolated from bone marrow, they can be used in various tissue engineering strategies. In this study, we assessed whether MSCs can differentiate into multiple skin cell types including keratinocytes and contribute to wound repair. First, we found keratin 14-positive cells, presumed to be keratinocytes that transdifferentiated from MSCs in vitro. Next, we assessed whether MSCs can transdifferentiate into multiple skin cell types in vivo. At sites of mouse wounds that had been i.v. injected with MSCs derived from GFP transgenic mice, we detected GFP-positive cells associated with specific markers for keratinocytes, endothelial cells, and pericytes. Because MSCs are predominantly located in bone marrow, we investigated the main MSC recruitment mechanism. MSCs expressed several chemokine receptors; especially CCR7, which is a receptor of SLC/CCL21, that enhanced MSC migration. Finally, MSC-injected mice underwent rapid wound repaired. Furthermore, intradermal injection of SLC/CCL21 increased the migration of MSCs, which resulted in an even greater acceleration of wound repair. Taken together, we have demonstrated that MSCs contribute to wound repair via processes involving MSCs differentiation various cell components of the skin.

Moyamoya disease: current concepts and future perspectives

Abstract: Moyamoya disease is an uncommon cerebrovascular disease that is characterised by progressive stenosis of the terminal portion of the internal carotid artery and its main branches. The disease is associated with the development of dilated, fragile collateral vessels at the base of the brain, which are termed moyamoya vessels. The incidence of moyamoya disease is high in east Asia, and familial forms account for about 15% of patients with this disease. Moyamoya disease has several unique clinical features, which include two peaks of age distribution at 5 years and at about 40 years. Most paediatric patients have ischaemic attacks, whereas adult patients can have ischaemic attacks, intracranial bleeding, or both. Extracranial-intracranial arterial bypass, including anastomosis of the superficial temporal artery to the middle cerebral artery and indirect bypass, can help prevent further ischaemic attacks, although the beneficial effect on haemorrhagic stroke is still not clear. In this Review, we summarise the epidemiology, aetiology, clinical features, diagnosis, surgical treatment, and outcomes of moyamoya disease. Recent updates and future perspectives for moyamoya disease will also be discussed.

DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes

Abstract: Silencing of transposable elements occurs during fetal gametogenesis in males via de novo DNA methylation of their regulatory regions. The loss of MILI (miwi-like) and MIWI2 (mouse piwi 2), two mouse homologs of Drosophila Piwi, activates retrotransposon gene expression by impairing DNA methylation in the regulatory regions of the retrotransposons. However, as it is unclear whether the defective DNA methylation in the mutants is due to the impairment of de novo DNA methylation, we analyze DNA methylation and Piwi-interacting small RNA (piRNA) expression in wild-type, MILI-null, and MIWI2-null male fetal germ cells. We reveal that defective DNA methylation of the regulatory regions of the Line-1 (long interspersed nuclear elements) and IAP (intracisternal A particle) retrotransposons in the MILI-null and MIWI2-null male germ cells takes place at the level of de novo methylation. Comprehensive analysis shows that the piRNAs of fetal germ cells are distinct from those previously identified in neonatal and adult germ cells. The expression of piRNAs is reduced under MILI- and MIWI2-null conditions in fetal germ cells, although the extent of the reduction differs significantly between the two mutants. Our data strongly suggest that MILI and MIWI2 play essential roles in establishing de novo DNA methylation of retrotransposons in fetal male germ cells.

The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB.

Abstract: BACKGROUND: Since publication in 2000 of the Second International Consensus Report on Diagnosis and Classification of Epidermolysis Bullosa, many advances have been made to our understanding of this group of diseases, both clinically and molecularly. At the same time, new epidermolysis bullosa (EB) subtypes have been described and similarities with some other diseases have been identified. OBJECTIVE: We sought to arrive at a new consensus of the classification of EB subtypes. RESULTS: We now present a revised classification system that takes into account the new advances, as well as encompassing other inherited diseases that should also be included within the EB spectrum, based on the presence of blistering and mechanical fragility. Current recommendations are made on the use of specific diagnostic tests, with updates on the findings known to occur within each of the major EB subtypes. Electronic links are also provided to informational and laboratory resources of particular benefit to clinicians and their patients. LIMITATIONS: As more becomes known about this disease, future modifications may be needed. The classification system has been designed with sufficient flexibility for these modifications. CONCLUSION: This revised classification system should assist clinicians in accurately diagnosing and subclassifying patients with EB.

Pristine Simple Oxides as Visible Light Driven Photocatalysts: Highly Efficient Decomposition of Organic Compounds over Platinum-Loaded Tungsten Oxide

Abstract: Tungsten oxide loaded with nanoparticulate platinum is demonstrated to exhibit high activity for the decomposition of organic compounds both in liquid and gas phases; the activity was almost comparable to that of TiO2 under UV light irradiation and much higher than that of nitrogen-doped TiO2 under visible irradiation.

Regulation of oocyte maturation in fish.

Abstract: A period of oocyte growth is followed by a process called oocyte maturation (the resumption of meiosis) which occurs prior to ovulation and is a prerequisite for successful fertilization. Our studies using fish models have revealed that oocyte maturation is a three-step induction process involving gonadotropin (LH), maturation-inducing hormone (MIH), and maturation-promoting factor (MPF). LH acts on the ovarian follicle layer to produce MIH (17α, 20β-dihydroxy-4-pregnen-3-one, 17α, 20β-DP, in most fishes). The interaction of ovarian thecal and granulosa cell layers (two-cell type model), is required for the synthesis of 17α,20β-DP. The dramatic increase in the capacity of postvitellogenic follicles to produce 17α,20β-DP in response to LH is correlated with decreases in P450c17 (P450c17-I) and P450 aromatase (oP450arom) mRNA and increases in the novel form of P450c17 (P450c17-II) and 20β-hydroxysteroid dehydrogenase (20β-HSD) mRNA. Transcription factors such as Ad4BP/SF-1, Foxl2, and CREB may be involved in the regulation of expression of these steroidogenic enzymes. A distinct family of G-protein-coupled membrane-bound MIH receptors has been shown to mediate non-genomic actions of 17α, 20β-DP. The MIH signal induces the de novo synthesis of cyclin B from the stored mRNA, which activates a preexisting 35 kDa cdc2 kinase via phosphorylation of its threonine 161 by cyclin-dependent kinase activating kinase, thus producing the 34 kDa active cdc2 (active MPF). Upon egg activation, MPF is inactivated by degradation of cyclin B. This process is initiated by the 26S proteasome through the first cut in its NH2 terminus at lysine 57.

Bruxism physiology and pathology: an overview for clinicians*

Abstract: Awake bruxism is defined as the awareness of jaw clenching. Its prevalence is reported to be 20% among the adult population. Awake bruxism is mainly associated with nervous tic and reactions to stress. The physiology and pathology of awake bruxism is unknown, although stress and anxiety are considered to be risk factors. During sleep, awareness of tooth grinding (as noted by sleep partner or family members) is reported by 8% of the population. Sleep bruxism is a behaviour that was recently classified as a 'sleep-related movement disorder'. There is limited evidence to support the role of occlusal factors in the aetiology of sleep bruxism. Recent publications suggest that sleep bruxism is secondary to sleep-related micro-arousals (defined by a rise in autonomic cardiac and respiratory activity that tends to be repeated 8-14 times per hour of sleep). The putative roles of hereditary (genetic) factors and of upper airway resistance in the genesis of rhythmic masticatory muscle activity and of sleep bruxism are under investigation. Moreover, rhythmic masticatory muscle activity in sleep bruxism peaks in the minutes before rapid eye movement sleep, which suggests that some mechanism related to sleep stage transitions exerts an influence on the motor neurons that facilitate the onset of sleep bruxism. Finally, it remains to be clarified when bruxism, as a behaviour found in an otherwise healthy population, becomes a disorder, i.e. associated with consequences (e.g. tooth damage, pain and social/marital conflict) requires intervention by a clinician.

Influence of the Gulf Stream on the troposphere

Abstract: The Gulf Stream is a warm Atlantic current that transports heat northward, keeping Western Europe significantly warmer than North America in winter. It is known to influence short-term weather phenomena such as surface winds and cyclone formation, but its effects on longer-term climate and at higher levels in the atmosphere are poorly understood. Now a combination of weather analyses, satellite data and an atmospheric general circulation model reveals that the Gulf Stream's influence is felt well above the near-surface portion of the atmosphere. The current anchors a tall wall of atmospheric upward motion that penetrates into the upper troposphere and supports deep raining clouds. This provides a pathway by which the Gulf Stream can affect local climate, and possibly climate in remote regions via an effect on planetary wave propagation. The cover graphic represents surface current speeds in blue-white colours (white is the fastest) and upward wind velocities in yellow-red colours (red for stronger winds), along with land-surface topography in eastern North America. The Gulf Stream's influence on the atmosphere is examined using a combination of operational weather analyses and satellite observations. The results indicate that the Gulf Stream anchors a rain band in which upward motion of air penetrates deep into the upper troposphere, well above the near-surface portion of the atmosphere. These mechanisms provide a pathway by which the Gulf Stream can affect local climate, and possibly also climate in remote regions. The Gulf Stream transports large amounts of heat from the tropics to middle and high latitudes, and thereby affects weather phenomena such as cyclogenesis1,2 and low cloud formation3. But its climatic influence, on monthly and longer timescales, remains poorly understood. In particular, it is unclear how the warm current affects the free atmosphere above the marine atmospheric boundary layer. Here we consider the Gulf Stream’s influence on the troposphere, using a combination of operational weather analyses, satellite observations and an atmospheric general circulation model4. Our results reveal that the Gulf Stream affects the entire troposphere. In the marine boundary layer, atmospheric pressure adjustments to sharp sea surface temperature gradients lead to surface wind convergence, which anchors a narrow band of precipitation along the Gulf Stream. In this rain band, upward motion and cloud formation extend into the upper troposphere, as corroborated by the frequent occurrence of very low cloud-top temperatures. These mechanisms provide a pathway by which the Gulf Stream can affect the atmosphere locally, and possibly also in remote regions by forcing planetary waves5,6. The identification of this pathway may have implications for our understanding of the processes involved in climate change, because the Gulf Stream is the upper limb of the Atlantic meridional overturning circulation, which has varied in strength in the past7 and is predicted to weaken in response to human-induced global warming in the future8.

Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse

Abstract: Infection with cagA-positive Helicobacter pylori is associated with gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma of B cell origin. The cagA-encoded CagA protein is delivered into gastric epithelial cells via the bacterial type IV secretion system and, upon tyrosine phosphorylation by Src family kinases, specifically binds to and aberrantly activates SHP-2 tyrosine phosphatase, a bona fide oncoprotein in human malignancies. CagA also elicits junctional and polarity defects in epithelial cells by interacting with and inhibiting partitioning-defective 1 (PAR1)/microtubule affinity-regulating kinase (MARK) independently of CagA tyrosine phosphorylation. Despite these CagA activities that contribute to neoplastic transformation, a causal link between CagA and in vivo oncogenesis remains unknown. Here, we generated transgenic mice expressing wild-type or phosphorylation-resistant CagA throughout the body or predominantly in the stomach. Wild-type CagA transgenic mice showed gastric epithelial hyperplasia and some of the mice developed gastric polyps and adenocarcinomas of the stomach and small intestine. Systemic expression of wild-type CagA further induced leukocytosis with IL-3/GM-CSF hypersensitivity and some mice developed myeloid leukemias and B cell lymphomas, the hematological malignancies also caused by gain-of-function SHP-2 mutations. Such pathological abnormalities were not observed in transgenic mice expressing phosphorylation-resistant CagA. These results provide first direct evidence for the role of CagA as a bacterium-derived oncoprotein (bacterial oncoprotein) that acts in mammals and further indicate the importance of CagA tyrosine phosphorylation, which enables CagA to deregulate SHP-2, in the development of H. pylori-associated neoplasms.

Placing the face in context: cultural differences in the perception of facial emotion.

Abstract: Two studies tested the hypothesis that in judging people's emotions from their facial expressions, Japanese, more than Westerners, incorporate information from the social context. In Study 1, participants viewed cartoons depicting a happy, sad, angry, or neutral person surrounded by other people expressing the same emotion as the central person or a different one. The surrounding people's emotions influenced Japanese but not Westerners' perceptions of the central person. These differences reflect differences in attention, as indicated by eye-tracking data (Study 2): Japanese looked at the surrounding people more than did Westerners. Previous findings on East-West differences in contextual sensitivity generalize to social contexts, suggesting that Westerners see emotions as individual feelings, whereas Japanese see them as inseparable from the feelings of the group.

Reversible Mechanochromic Luminescence of [(C6F5Au)2(μ-1,4-Diisocyanobenzene)]

Abstract: Reversible mechanochromic luminescence of [(C6F5Au)2(mu-1,4-diisocyanobenzene)] is reported. Grinding of the complex induced a photoluminescent color change, which was restored by exposure to a solvent. This cycle was repeated 20 times with no color degradation in the emissions. Their optical properties, X-ray crystallographic analysis, IR, and XRD measurements strongly suggested that the change in the molecular arrangement is responsible for this mechanochromic property. Intermolecular aurophilic bondings presumably play a key role in the altered emission.

The amphioxus genome illuminates vertebrate origins and cephalochordate biology

Abstract: Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago To improve our understanding of chordate evolution and the origin of vertebrates, we intensively searched for particular genes, gene families, and conserved noncoding elements in the sequenced genome of the cephalochordate Branchiostoma floridae, commonly called amphioxus or lancelets Special attention was given to homeobox genes, opsin genes, genes involved in neural crest development, nuclear receptor genes, genes encoding components of the endocrine and immune systems, and conserved cis-regulatory enhancers The amphioxus genome contains a basic set of chordate genes involved in development and cell signaling, including a fifteenth Hox gene This set includes many genes that were co-opted in vertebrates for new roles in neural crest development and adaptive immunity However, where amphioxus has a single gene, vertebrates often have two, three, or four paralogs derived from two whole-genome duplication events In addition, several transcriptional enhancers are conserved between amphioxus and vertebrates--a very wide phylogenetic distance In contrast, urochordate genomes have lost many genes, including a diversity of homeobox families and genes involved in steroid hormone function The amphioxus genome also exhibits derived features, including duplications of opsins and genes proposed to function in innate immunity and endocrine systems Our results indicate that the amphioxus genome is elemental to an understanding of the biology and evolution of nonchordate deuterostomes, invertebrate chordates, and vertebrates

The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription

Abstract: The nuclear lamins function in the regulation of replication, transcription, and epigenetic modifications of chromatin. However, the mechanisms responsible for these lamin functions are poorly understood. We demonstrate that A- and B-type lamins form separate, but interacting, stable meshworks in the lamina and have different mobilities in the nucleoplasm as determined by fluorescence correlation spectroscopy (FCS). Silencing lamin B1 (LB1) expression dramatically increases the lamina meshwork size and the mobility of nucleoplasmic lamin A (LA). The changes in lamina mesh size are coupled to the formation of LA/C-rich nuclear envelope blebs deficient in LB2. Comparative genomic hybridization (CGH) analyses of microdissected blebs, fluorescence in situ hybridization (FISH), and immunofluorescence localization of modified histones demonstrate that gene-rich euchromatin associates with the LA/C blebs. Enrichment of hyperphosphorylated RNA polymerase II (Pol II) and histone marks for active transcription suggest that blebs are transcriptionally active. However, in vivo labeling of RNA indicates that transcription is decreased, suggesting that the LA/C-rich microenvironment induces promoter proximal stalling of Pol II. We propose that different lamins are organized into separate, but interacting, microdomains and that LB1 is essential for their organization. Our evidence suggests that the organization and regulation of chromatin are influenced by interconnections between these lamin microdomains.

Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus

Abstract: Our scientific knowledge of pemphigus has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in pemphigus. A major obstacle in comparing therapeutic outcomes between centers is the lack of generally accepted definitions and measurements for the clinical evaluation of patients with pemphigus. Common terms and end points of pemphigus are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. This consensus statement from the International Pemphigus Committee represents 2 years of collaborative efforts to attain mutually acceptable common definitions for pemphigus. These should assist in development of consistent reporting of outcomes in future studies.

Stellar Abundances for the Galactic Archeology (SAGA) Database — Compilation of the Characteristics of Known Extremely Metal-Poor Stars

Abstract: We describe the construction of a database of extremely metal-poor (EMP) stars in the Galaxy. Our database contains detailed elemental abundances, reported equivalent widths, atmospheric parameters, photometry, and binarity status, compiled from papers in the literature that report on studies of EMP halo stars with [Fe=H] �� 2.5. The compilation procedures for this database were designed to assemble data effectively from electronic tables available from online journals. We have also developed ad ata retrieval system that enables data searches by various criteria and illustrations to explore relationships between stored variables. Currently, our sample includes 1212 unique stars (many of which are studied by more than one group) with more than 15000 individual reported elemental abundances, covering relevant papers published by 2007 December. We discuss the global characteristics of the present database, as revealed by the EMP stars observed to date. For stars with [Fe=H] �� 2.5, the number of giants with reported abundances is larger than that of dwarfs by a factor of two. The fraction of carbon-rich stars (among the sample for which the carbon abundance is reported) amounts to � 30% for [Fe=H] �� 2.5. We find that known binaries exhibit different distributions of the orbital period, according to whether they are giants or dwarfs, and also as a function of the metallicity, although the total sample of such stars is still quite small.

Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart

Abstract: Understanding cellular response to environmental stress has broad implications for human disease AMP-activated protein kinase (AMPK) orchestrates the regulation of energy-generating and -consuming pathways, and protects the heart against ischaemic injury and apoptosis A role for circulating hormones such as adiponectin and leptin in the activation of AMPK has received recent attention Whether local autocrine and paracrine factors within target organs such as the heart modulate AMPK is unknown Here we show that macrophage migration inhibitory factor (MIF), an upstream regulator of inflammation, is released in the ischaemic heart, where it stimulates AMPK activation through CD74, promotes glucose uptake and protects the heart during ischaemia-reperfusion injury Germline deletion of the Mif gene impairs ischaemic AMPK signalling in the mouse heart Human fibroblasts with a low-activity MIF promoter polymorphism have diminished MIF release and AMPK activation during hypoxia Thus, MIF modulates the activation of the cardioprotective AMPK pathway during ischaemia, functionally linking inflammation and metabolism in the heart We anticipate that genetic variation in MIF expression may impact on the response of the human heart to ischaemia by the AMPK pathway, and that diagnostic MIF genotyping might predict risk in patients with coronary artery disease

The Stellar Abundances for Galactic Archeology (SAGA) Database - Compilation of the Characteristics of Known Extremely Metal-Poor Stars

Abstract: We describe the construction of a database of extremely metal-poor (EMP) stars in the Galactic halo whose elemental abundances have been determined. Our database contains detailed elemental abundances, reported equivalent widths, atmospheric parameters, photometry, and binarity status, compiled from papers in the recent literature that report studies of EMP halo stars with [Fe/H] < -2.5. The compilation procedures for this database have been designed to assemble the data effectively from electronic tables available from online journals. We have also developed a data retrieval system that enables data searches by various criteria, and permits the user to explore relationships between the stored variables graphically. Currently, our sample includes 1212 unique stars (many of which are studied by more than one group) with more than 15000 individual reported elemental abundances, covering all of the relevant papers published by December 2007. We discuss the global characteristics of the present database, as revealed by the EMP stars observed to date. For stars with [Fe/H] < -2.5, the number of giants with reported abundances is larger than that of dwarfs by a factor of two. The fraction of carbon-rich stars (among the sample for which the carbon abundance is reported) amount to ~30 % for [Fe/H] < -2.5. We find that known binaries exhibit different distributions of orbital period, according to whether they are giants or dwarfs, and also as a function of metallicity, although the total sample of such stars is still quite small.

Structural basis of target recognition by Atg8/LC3 during selective autophagy.

Abstract: Autophagy is a non-selective bulk degradation process in which isolation membranes enclose a portion of cytoplasm to form double-membrane vesicles, called autophagosomes, and deliver their inner constituents to the lytic compartments. Recent studies have also shed light on another mode of autophagy that selectively degrades various targets. Yeast Atg8 and its mammalian homologue LC3 are ubiquitin-like modifiers that are localized on isolation membranes and play crucial roles in the formation of autophagosomes. These proteins are also involved in selective incorporation of specific cargo molecules into autophagosomes, in which Atg8 and LC3 interact with Atg19 and p62, receptor proteins for vacuolar enzymes and disease-related protein aggregates, respectively. Using X-ray crystallography and NMR, we herein report the structural basis for Atg8–Atg19 and LC3–p62 interactions. Remarkably, Atg8 and LC3 were shown to interact with Atg19 and p62, respectively, in a quite similar manner: they recognized the side-chains of Trp and Leu in a four-amino acid motif, WXXL, in Atg19 and p62 using hydrophobic pockets conserved among Atg8 homologues. Together with mutational analyses, our results show the fundamental mechanism that allows Atg8 homologues, in association with WXXL-containing proteins, to capture specific cargo molecules, thereby endowing isolation membranes and/or their assembly machineries with target selectivity.

FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets

Abstract: White adipocytes are unique in that they contain large unilocular lipid droplets that occupy most of the cytoplasm. To identify genes involved in the maintenance of mature adipocytes, we expressed dominant-negative PPARγ in 3T3-L1 cells and performed a microarray screen. The fat-specific protein of 27 kDa (FSP27) was strongly downregulated in this context. FSP27 expression correlated with induction of differentiation in cultured preadipocytes, and the protein localized to lipid droplets in murine white adipocytes in vivo. Ablation of FSP27 in mice resulted in the formation of multilocular lipid droplets in these cells. Furthermore, FSP27-deficient mice were protected from diet-induced obesity and insulin resistance and displayed an increased metabolic rate due to increased mitochondrial biogenesis in white adipose tissue (WAT). Depletion of FSP27 by siRNA in murine cultured white adipocytes resulted in the formation of numerous small lipid droplets, increased lipolysis, and decreased triacylglycerol storage, while expression of FSP27 in COS cells promoted the formation of large lipid droplets. Our results suggest that FSP27 contributes to efficient energy storage in WAT by promoting the formation of unilocular lipid droplets, thereby restricting lipolysis. In addition, we found that the nature of lipid accumulation in WAT appears to be associated with maintenance of energy balance and insulin sensitivity.

Ubiquitous 8 and 29 kDa gold:alkanethiolate cluster compounds: mass-spectrometric determination of molecular formulas and structural implications.

Abstract: The molecular formulas and charge state distributions of thus-far known ubiquitous alkanethiolate-protected gold clusters with core-masses of 8 and 29 kDa were assessed using electrospray ionization mass spectrometry. The 8 and 29 kDa clusters were determined to be composed of single species, [Au38(SCn)24]z and [Au144(SCn)59]z, respectively, with charge states of z ≥ 0. Possible geometric structures for Au38(SCn)24 and Au144(SCn)59 are discussed, based on the structures of relevant systems that have been recently determined experimentally and theoretically: [Au25(SR)18]− and Au102(SR)44, in which the Au cores are protected by monomers [−SR−Au−SR−] and/or dimers [−SR−Au−SR−Au−SR−]. Their preferential formation and chemical robustness are proposed as being associated with high stability due to geometric factors, while the Au−thiolate interface takes on common motifs regardless of the underlying Au core.

Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis

Abstract: Objectives: A large-scale post-marketing surveillance (PMS) study was carried out to determine the safety profile of infliximab in Japanese patients with rheumatoid arthritis (RA). Methods: The PMS study was performed for all patients with RA who were treated with infliximab. They were consecutively registered in the PMS study at the initiation of infliximab treatment and were prospectively monitored with all adverse events noted for a period of 6 months. All case reports, which include safety-related events, were collected monthly. Results: Adverse drug reactions (ADRs) were assessed for 6 months in 5,000 patients who were consecutively enrolled in the PMS study. The incidence rates of total and serious ADRs were 28.0% and 6.2%, respectively. “Infections” or “respiratory disorders” were most commonly observed among serious ADRs. Bacterial pneumonia developed in 2.2%, tuberculosis in 0.3%, suspected Pneumocystis jiroveci pneumonia (PCP) in 0.4%, and interstitial pneumonitis in 0.5%. Bacterial pneumonia (for which individuals of male gender, of older age and those with advanced rheumatoid arthritis and comorbid respiratory disease were most at risk) began to develop immediately after the start of treatment, while tuberculosis, PCP and interstitial pneumonitis developed about one month later. Serious infusion reactions were observed in 0.5% and were more likely to occur in patients who had participated in previous clinical trials of infliximab. Conclusion: This post-marketing surveillance study of patients treated with infliximab showed that infliximab in combination with low dose MTX was well tolerated in Japanese patients with active RA.

Control of InAs Nanowire Growth Directions on Si

Abstract: We report on control of growth directions of InAs nanowires on Si substrate. We achieved to integrate vertical InAs nanowires on Si by modifying initial Si(111) surface in selective-area metal-organic vapor phase epitaxy with flow-rate modulation mode at low temperature. Cross-sectional transmission electron microscope and Raman scattering showed that misfit dislocation with local strains were accommodated in the interface.

Mitochondrial oxidative stress and dysfunction in myocardial remodelling.

Abstract: Recent experimental and clinical studies have suggested that oxidative stress is enhanced in myocardial remodelling and failure. The production of oxygen radicals is increased in the failing heart, whereas normal antioxidant enzyme activities are preserved. Mitochondrial electron transport is an enzymatic source of oxygen radical generation and can be a therapeutic target against oxidant-induced damage in the failing myocardium. Chronic increases in oxygen radical production in the mitochondria can lead to a catastrophic cycle of mitochondrial DNA (mtDNA) damage as well as functional decline, further oxygen radical generation, and cellular injury. Reactive oxygen species induce myocyte hypertrophy, apoptosis, and interstitial fibrosis by activating matrix metalloproteinases. These cellular events play an important role in the development and progression of maladaptive myocardial remodelling and failure. Therefore, oxidative stress and mtDNA damage are good therapeutic targets. Overexpression of the genes for peroxiredoxin-3 (Prx-3), a mitochondrial antioxidant, or mitochondrial transcription factor A (TFAM), could ameliorate the decline in mtDNA copy number in failing hearts. Consistent with alterations in mtDNA, the decrease in mitochondrial function was also prevented. Therefore, the activation of Prx-3 or TFAM gene expression could ameliorate the pathophysiological processes seen in mitochondrial dysfunction and myocardial remodelling. Inhibition of oxidative stress and mtDNA damage could be novel and effective treatment strategies for heart failure.