HEAT: a New Tool for Gene Set Enrichment Analysis Using Comprehensive Annotation of Human Genes in H-InvDB

H-InvDB Enrichment Analysis Tool (HEAT) is a new data-mining tool for gene set enrichment analysis based on comprehensive annotations of human genes in H-InvDB. HEAT searches for H-InvDB annotations that are significantly enriched in a user-defined gene set, as compared with the entire H-InvDB representative transcripts. The advantage of HEAT is the wide variety of annotation items used for its analysis: chromosomal bands, InterPro functional domains, Gene Ontology terms, KEGG pathways, H-InvDB gene families/groups, SCOP structural domains, subcellular localization predicted by using the Wolf-PSORT program, tissue-specific gene expression as defined in the H-ANGEL database, and transcription factor binding sites in promoter regions based on JASPAR. HEAT accepts lists of human gene identifiers (IDs) including HUGO gene symbols, accession numbers of INSD (DDBJ/EMBL/GenBank), UniProt accession numbers, Gene IDs, Ensembl Gene IDs, H-InvDB Transcript IDs (HIT) and Locus IDs (HIX), etc. Then, HEAT converts the accepted IDs into HIX using the ID Converter System ("http://biodb.jp/":http://biodb.jp/), collects various annotations of H-InvDB representative transcripts, and conducts statistical tests by using Fisher's exact probability. The output of HEAT is a simple report of annotations commonly found among the query genes, which is very useful to grasp the property of a particular gene set. HEAT is freely available at "http://hinv.jp/HEAT/":http://hinv.jp/HEAT/

Descendants of the first stars: the distinct chemical signature of second generation stars

Extremely metal-poor (EMP) stars in the Milky Way (MW) allow us to infer the properties of their progenitors by comparing their chemical composition to the metal yields of the first supernovae. This method is most powerful when applied to mono-enriched stars, i.e. stars that formed from gas that was enriched by only one previous supernova. We present a novel diagnostic to identify this subclass of EMP stars. We model the first generations of star formation semi-analytically, based on dark matter halo merger trees that yield MW-like halos at the present day. Radiative and chemical feedback are included self-consistently and we trace all elements up to zinc. Mono-enriched stars account for only $\sim 1\%$ of second generation stars in our fiducial model and we provide an analytical formula for this probability. We also present a novel analytical diagnostic to identify mono-enriched stars, based on the metal yields of the first supernovae. This new diagnostic allows us to derive our main results independently from the specific assumptions made regarding Pop III star formation, and we apply it to a set of observed EMP stars to demonstrate its strengths and limitations. Our results may provide selection criteria for current and future surveys and therefore contribute to a deeper understanding of EMP stars and their progenitors.Comment: 18 pages, 20 figures, published in MNRA

A Minimum Dilution Scenario for Supernovae and Consequences for Extremely Metal-Poor Stars

© 2020 The Author(s) 2020 Published by Oxford University Press on behalf of the Royal Astronomical Society.To date no metal-free stars have been identified by direct observations. The most common method of constraining their properties is searching the spectra of the most metal-poor stars for the chemical elements created in the first stars and their supernova (SN). In this approach, modelled SN yields are compared to the observed abundance patterns in extremely metal-poor stars. The method typically only uses the abundance ratios, i.e. the yields are diluted to the observed level. Following the usual assumption of spherical symmetry we compute a simple lower limit of the mass an SN can mix with and find that it is consistent with all published simulations of early chemical enrichment in the interstellar medium. For three different cases, we demonstrate that this dilution limit can change the conclusions from the abundance fitting. There is a large discrepancy between the dilution found in simulations of SN explosions in minihaloes and the dilution assumed in many abundance fits. Limiting the dilution can significantly alter the likelihood of which supernovae are possible progenitors of observed CEMP-no stars. In particular, some of the faint, very low yield SNe, which have been suggested as models for the abundance pattern of SMSS0313-6708, cannot explain the measured metal abundances, as their predicted metal yields are too small by two orders of magnitude. Altogether, the new dilution model presented here emphasizes the need to better understand the mixing and dilution behaviour of aspherical SNe.Peer reviewedFinal Accepted Versio

Comparative Proteomic Analysis of Methanothermobacter themautotrophicus ΔH in Pure Culture and in Co-Culture with a Butyrate-Oxidizing Bacterium

To understand the physiological basis of methanogenic archaea living on interspecies H2 transfer, the protein expression of a hydrogenotrophic methanogen, Methanothermobacter thermautotrophicus strain ΔH, was investigated in both pure culture and syntrophic coculture with an anaerobic butyrate oxidizer Syntrophothermus lipocalidus strain TGB-C1 as an H2 supplier. Comparative proteomic analysis showed that global protein expression of methanogen cells in the model coculture was substantially different from that of pure cultured cells. In brief, in syntrophic coculture, although methanogenesis-driven energy generation appeared to be maintained by shifting the pathway to the alternative methyl coenzyme M reductase isozyme I and cofactor F420-dependent process, the machinery proteins involved in carbon fixation, amino acid synthesis, and RNA/DNA metabolisms tended to be down-regulated, indicating restrained cell growth rather than vigorous proliferation. In addition, our proteome analysis revealed that α subunits of proteasome were differentially acetylated between the two culture conditions. Since the relevant modification has been suspected to regulate proteolytic activity of the proteasome, the global protein turnover rate could be controlled under syntrophic growth conditions. To our knowledge, the present study is the first report on N-acetylation of proteasome subunits in methanogenic archaea. These results clearly indicated that physiological adaptation of hydrogenotrophic methanogens to syntrophic growth is more complicated than that of hitherto proposed

Mitochondrial Genome Sequences Effectively Reveal the Phylogeny of Hylobates Gibbons

BACKGROUND: Uniquely among hominoids, gibbons exist as multiple geographically contiguous taxa exhibiting distinctive behavioral, morphological, and karyotypic characteristics. However, our understanding of the evolutionary relationships of the various gibbons, especially among Hylobates species, is still limited because previous studies used limited taxon sampling or short mitochondrial DNA (mtDNA) sequences. Here we use mtDNA genome sequences to reconstruct gibbon phylogenetic relationships and reveal the pattern and timing of divergence events in gibbon evolutionary history. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the mitochondrial genomes of 51 individuals representing 11 species belonging to three genera (Hylobates, Nomascus and Symphalangus) using the high-throughput 454 sequencing system with the parallel tagged sequencing approach. Three phylogenetic analyses (maximum likelihood, Bayesian analysis and neighbor-joining) depicted the gibbon phylogenetic relationships congruently and with strong support values. Most notably, we recover a well-supported phylogeny of the Hylobates gibbons. The estimation of divergence times using Bayesian analysis with relaxed clock model suggests a much more rapid speciation process in Hylobates than in Nomascus. CONCLUSIONS/SIGNIFICANCE: Use of more than 15 kb sequences of the mitochondrial genome provided more informative and robust data than previous studies of short mitochondrial segments (e.g., control region or cytochrome b) as shown by the reliable reconstruction of divergence patterns among Hylobates gibbons. Moreover, molecular dating of the mitogenomic divergence times implied that biogeographic change during the last five million years may be a factor promoting the speciation of Sundaland animals, including Hylobates species

Innovations for Sustainability: Pathways to an efficient and post-pandemic future

3rd Report prepared by The World in 2050 initiativ

Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice.

Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix. Transfection assays demonstrated that the gene mutations destabilize the molecule, dramatically reducing HYAL2 protein levels. Consistent with the clinical presentation in affected individuals, investigations of Hyal2-/- mice revealed craniofacial abnormalities, including submucosal cleft palate. In addition, cor triatriatum sinister and hearing loss, identified in a proportion of Hyal2-/- mice, were also found as incompletely penetrant features in affected humans. Taken together our findings identify a new genetic cause of orofacial clefting in humans and mice, and define the first molecular cause of human cor triatriatum sinister, illustrating the fundamental importance of HYAL2 and hyaluronan turnover for normal human and mouse development

Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines

This article discusses the definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis. Acute cholangitis and cholecystitis mostly originate from stones in the bile ducts and gallbladder. Acute cholecystitis also has other causes, such as ischemia; chemicals that enter biliary secretions; motility disorders associated with drugs; infections with microorganisms, protozoa, and parasites; collagen disease; and allergic reactions. Acute acalculous cholecystitis is associated with a recent operation, trauma, burns, multisystem organ failure, and parenteral nutrition. Factors associated with the onset of cholelithiasis include obesity, age, and drugs such as oral contraceptives. The reported mortality of less than 10% for acute cholecystitis gives an impression that it is not a fatal disease, except for the elderly and/or patients with acalculous disease. However, there are reports of high mortality for cholangitis, although the mortality differs greatly depending on the year of the report and the severity of the disease. Even reports published in and after the 1980s indicate high mortality, ranging from 10% to 30% in the patients, with multiorgan failure as a major cause of death. Because many of the reports on acute cholecystitis and cholangitis use different standards, comparisons are difficult. Variations in treatment and risk factors influencing the mortality rates indicate the necessity for standardized diagnostic, treatment, and severity assessment criteria

JPN Guidelines for the management of acute pancreatitis: epidemiology, etiology, natural history, and outcome predictors in acute pancreatitis

Acute pancreatitis is a common disease with an annual incidence of between 5 and 80 people per 100 000 of the population. The two major etiological factors responsible for acute pancreatitis are alcohol and cholelithiasis (gallstones). The proportion of patients with pancreatitis caused by alcohol or gallstones varies markedly in different countries and regions. The incidence of acute alcoholic pancreatitis is considered to be associated with high alcohol consumption. Although the incidence of alcoholic pancreatitis is much higher in men than in women, there is no difference in sexes in the risk involved after adjusting for alcohol intake. Other risk factors include endoscopic retrograde cholangiopancreatography, surgery, therapeutic drugs, HIV infection, hyperlipidemia, and biliary tract anomalies. Idiopathic acute pancreatitis is defined as acute pancreatitis in which the etiological factor cannot be specified. However, several studies have suggested that this entity includes cases caused by other specific disorders such as microlithiasis. Acute pancreatitis is a potentially fatal disease with an overall mortality of 2.1%–7.8%. The outcome of acute pancreatitis is determined by two factors that reflect the severity of the illness: organ failure and pancreatic necrosis. About half of the deaths in patients with acute pancreatitis occur within the first 1–2 weeks and are mainly attributable to multiple organ dysfunction syndrome (MODS). Depending on patient selection, necrotizing pancreatitis develops in approximately 10%–20% of patients and the mortality is high, ranging from 14% to 25% of these patients. Infected pancreatic necrosis develops in 30%–40% of patients with necrotizing pancreatitis and the incidence of MODS in such patients is high. The recurrence rate of acute pancreatitis is relatively high: almost half the patients with acute alcoholic pancreatitis experience a recurrence. When the gallstones are not treated, the risk of recurrence in gallstone pancreatitis ranges from 32% to 61%. After recovering from acute pancreatitis, about one-third to one-half of acute pancreatitis patients develop functional disorders, such as diabetes mellitus and fatty stool; the incidence of chronic pancreatitis after acute pancreatitis ranges from 3% to 13%. Nevertheless, many reports have shown that most patients who recover from acute pancreatitis regain good general health and return to their usual daily routine. Some authors have emphasized that endocrine function disorders are a common complication after severe acute pancreatitis has been treated by pancreatic resection