Vector Mesons in Nuclear Medium

We summarize the current theoretical and experimental status of the spectral change of the vector mesons in dense matter.Comment: 4 pages, Latex, talk at Quark Matter '9

Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2

AbstractThe yeast UBC9 gene encodes a protein with homology to the E2 ubiquitin-conjugating enzymes that mediate the attachment of ubiquitin to substrate proteins [1]. Depletion of Ubc9p arrests cells in G2 or early M phase and stabilizes B-type cyclins [1]. p18Ubc9, the Xenopus homolog of Ubc9p, associates specifically with p88RanGAP1 and p340RanBP2[2]. Ran-binding protein 2 (p340RanBP2) is a nuclear pore protein [3,4], and p88RanGAP1 is a modified form of RanGAP1, a GTPase-activating protein for the small GTPase Ran [2]. It has recently been shown that mammalian RanGAP1 can be conjugated with SUMO-1, a small ubiquitin-related modifier [5–7], and that SUMO-1 conjugation promotes RanGAP1's interaction with RanBP2 [2,5,6]. Here we show that p18Ubc9 acts as an E2-like enzyme for SUMO-1 conjugation, but not for ubiquitin conjugation. This suggests that the SUMO-1 conjugation pathway is biochemically similar to the ubiquitin conjugation pathway but uses a distinct set of enzymes and regulatory mechanisms. We also show that p18Ubc9 interacts specifically with the internal repeat domain of RanBP2, which is a substrate for SUMO-1 conjugation in Xenopus egg extracts

QCD Sum Rules, Scattering Length and the Vector Mesons in Nuclear Medium

Critical examination is made on the relation between the mass shift of vector mesons in nuclear medium and the vector-meson $-$ nucleon scattering length. We give detailed comparison between the QCD sum rule approach by two of the present authors (Phys. Rev. {\bf C46} (1992) R34) and the scattering-length approach by Koike (Phys. Rev. {\bf C51} (1995) 1488). It is shown that the latter approach is mortally flawed both technically and conceptually.Comment: 16 pages, latex, 4 figures appended as uu-encoded fil

Characterization and validation of Entamoeba histolytica pantothenate kinase as a novel anti-amebic drug target

The Coenzyme A (CoA), as a cofactor involved in >100 metabolic reactions, is essential to the basic biochemistry of life. Here, we investigated the CoA biosynthetic pathway of Entamoeba histolytica (E. histolytica), an enteric protozoan parasite responsible for human amebiasis. We identified four key enzymes involved in the CoA pathway: pantothenate kinase (PanK, EC 2.7.1.33), bifunctional phosphopantothenate-cysteine ligase/decarboxylase (PPCS-PPCDC), phosphopantetheine adenylyltransferase (PPAT) and dephospho-CoA kinase (DPCK). Cytosolic enzyme PanK, was selected for further biochemical, genetic, and phylogenetic characterization. Since E. histolytica PanK (EhPanK) is physiologically important and sufficiently divergent from its human orthologs, this enzyme represents an attractive target for the development of novel anti-amebic chemotherapies. Epigenetic gene silencing of PanK resulted in a significant reduction of PanK activity, intracellular CoA concentrations, and growth retardation in vitro, reinforcing the importance of this gene in E. histolytica. Furthermore, we screened the Kitasato Natural Products Library for inhibitors of recombinant EhPanK, and identified 14 such compounds. One compound demonstrated moderate inhibition of PanK activity and cell growth at a low concentration, as well as differential toxicity towards E. histolytica and human cells

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

On an Autopsy Case of Osteogenic Sarcoma

A review of the literature shows that osteogenic sarcoma is not rare, but the pathologic changes of this disease have not clearly reported yet. It is the purpose of this report to describe the pathohistogenetic changes with the clinical aspects in an autopsy case of osteogenic sarcoma. An adult man, 23 years of age, was admitted to the Hiraki Modical Clinic of the Okayama University Hospital, on August 24, 1953, complaining of chest ache and haemoptoe. The x-ray examination of the chest at that time showed base ball-sized, hard, lobulated masses in the both lungs. The pathological diagnosis was osteogenic sarcoma metastasized in both lungs from the right hemural tumor which amputated in a lower third of the right hemur four years ago. The average size of the tumors in lungs was 5-4 cm in diameter. They were usually nonencapsulated, and the cut surface was solid, firm, and grayish-white. Microscopically, there were two types of the histogenetic origins in tumors of the lung. The first histologic form, which is designated here as the "osteogenic cell sarcoma", showed the following characteristics. Microscopically, the component cells were fairly uniform and generally identical with osteolytic cells in various stages of fetal histogenetic cycles of the bone. There were some areas wherein the neoplastic cells showed atypical orientation and the nuclei were large and slightly dark. Mitoses and neoplasmic giant cells were found occasionally. In many neoplasmic cells the various courses of hyalinisation, carcification and osification were recognized. The second histologic form, which is labeled here as the "chondroblastic cell sarcoma", showed the following characteristics. Microscopically, neoplasmic tissues exhibited the chondroblastic cells, which made it possible to translate to osteolytic cells occasionally in some neoplasmic circumstances, and they were consisted of pleomorphic giant cells with the polymorphic cytoplasmas and numerous mitotic figures. As mentioned above, hyalinisation, carcification and osification were also found graduately in the cytoplasmas of such chondroblastic cells as osteolytic cells. In result of histologic examination, this case was malignant osteogenic sarcoma which showed extensive metastases in both lungs within five years

Pre-rectal portal scintigraphy: Comparison between technetium-99m, thallium-201, and iodine-123-HIPDM

SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

Deoxyinosine triphosphate induces MLH1/PMS2- and p53-dependent cell growth arrest and DNA instability in mammalian cells.

Deoxyinosine (dI) occurs in DNA either by oxidative deamination of a previously incorporated deoxyadenosine residue or by misincorporation of deoxyinosine triphosphate (dITP) from the nucleotide pool during replication. To exclude dITP from the pool, mammals possess specific hydrolysing enzymes, such as inosine triphosphatase (ITPA). Previous studies have shown that deficiency in ITPA results in cell growth suppression and DNA instability. To explore the mechanisms of these phenotypes, we analysed ITPA-deficient human and mouse cells. We found that both growth suppression and accumulation of single-strand breaks in nuclear DNA of ITPA-deficient cells depended on MLH1/PMS2. The cell growth suppression of ITPA-deficient cells also depended on p53, but not on MPG, ENDOV or MSH2. ITPA deficiency significantly increased the levels of p53 protein and p21 mRNA/protein, a well-known target of p53, in an MLH1-dependent manner. Furthermore, MLH1 may also contribute to cell growth arrest by increasing the basal level of p53 activity