Steroidogenic enzymes in the CP

Peripherally derived steroids affect steroid production in the brain via the blood–brain barrier. However, steroid concentrations are lower in the cerebrospinal fluid than those in the blood, indicating restricted influx of steroids because of their metabolization by choroid plexus (CP) epithelial cells. Here, we analyzed the gene expression of steroidogenic enzymes [cholesterol side-chain cleavage enzyme (P450scc), 17α-hydroxylase/C17-C20 lyase (P450c17), 3β-hydroxysteroid dehydrogenase (3β -HSD), 17β-hydroxysteroid dehydrogenase type 1 (17β -HSD1), aromatase (Cyp19a1), and 5α-reductase type 1 (5α -R1)]. These genes were expressed to a lesser extent in the CP than in the testis and to a similar extent in the cerebral cortex. However, P450scc levels were higher in the CP than in the cerebral cortex, whereas Cyp19a1 levels showed the opposite trend. We also evaluated the effects of orchiectomy and testosterone on the expression of these genes. P450c17 and 5α -R1 levels were unaffected by orchiectomy, whereas P450scc and 3β -HSD levels were increased and decreased, respectively. Cyp19a1 expression increased upon testosterone treatment, whereas that of 17β -HSD decreased upon orchiectomy or administration of testosterone. Immunohistochemistry analysis revealed that 17β -HSD was expressed in the cytoplasm of CP epithelial cells. These results indicate that CP epithelial cells synthesize and convert the certain types of steroids to contribute to the homeostasis of steroids in the brain

A case of giant urachal cyst in a neonate

AbstractWe report a case of giant urachal cyst in a neonate presenting characteristic features on fetal ultrasonography. A 28-year-old woman of 21 weeks gestation was referred to our hospital for evaluation of a cystic mass in the lower portion of the fetal abdomen. On fetal ultrasonography, at 23 weeks gestation, the two umbilical arteries in the base of the umbilical cord became separated from each other due to the fetal cyst. On fetal MRI, at 25 weeks gestation, the cyst was depicted as a unilocular serous cyst, independent of the surrounding organs such as the kidney, gallbladder and intestines. The cyst had no communication with the bladder or umbilical cord. A male infant was delivered at term. Although the infant was thriving and remained asymptomatic, an enhanced CT examination 13 days after birth showed the cyst was still present without any decrease in size. The infant underwent surgery to make a definite diagnosis and to prevent future complications. The cyst was excised without any complication and finally diagnosed as a urachal cyst based on morphological and pathological findings

Prompt and Long-term Prophylactic Effect of Closed Loop Stimulation against Paroxysmal Atrial Fibrillation in a Patient with Sick Sinus Syndrome

A 72-year-old woman with sick sinus syndrome (SSS), who had frequent paroxysmal atrial fibrillations (PAfs) and normal cardiac function, was admitted to our hospital due to syncope. PAfs frequently occurred during the first week after DDD pacemaker implantation (PMI), with closed loop stimulation (CLS) rate-adaptive mode off, but were completely suppressed during the second week, with CLS on, and had been well-controlled over three years thereafter. However, PAfs occasionally occurred under intense sympathetic activity during 6 months after PMI as well, and were effectively terminated by disopyramide which had anticholinergic effect. Thus, the development and maintenance of PAf were thought to be associated with destabilized cardiac autonomic activities, that is, sympathetic and parasympathetic dominance, respectively. Additionally, heart rate variability analyses after implementation of CLS revealed the restoration of sympathetic and parasympathetic components. Accordingly, CLS mode was considered to play a critical role in preventing PAf by reflecting autonomic activity in heart rhythm in this SSS patient

Transcriptome map of plant mitochondria reveals islands of unexpected transcribed regions

<p>Abstract</p> <p>Background</p> <p>Plant mitochondria contain a relatively large amount of genetic information, suggesting that their functional regulation may not be as straightforward as that of metazoans. We used a genomic tiling array to draw a transcriptomic atlas of <it>Oryza sativa japonica </it>(rice) mitochondria, which was predicted to be approximately 490-kb long.</p> <p>Results</p> <p>Whereas statistical analysis verified the transcription of all previously known functional genes such as the ones related to oxidative phosphorylation, a similar extent of RNA expression was frequently observed in the inter-genic regions where none of the previously annotated genes are located. The newly identified open reading frames (ORFs) predicted in these transcribed inter-genic regions were generally not conserved among flowering plant species, suggesting that these ORFs did not play a role in mitochondrial principal functions. We also identified two partial fragments of retrotransposon sequences as being transcribed in rice mitochondria.</p> <p>Conclusion</p> <p>The present study indicated the previously unexpected complexity of plant mitochondrial RNA metabolism. Our transcriptomic data (<it>Oryza sativa </it>Mitochondrial rna Expression Server: OsMES) is publicly accessible at [<url>http://bioinf.mind.meiji.ac.jp/cgi-bin/gbrowse/OsMes/#search</url>].</p

Dual-Matrix Domain-Wall: A Novel Technique for Generating Permutations by QUBO and Ising Models with Quadratic Sizes

The Ising model is defined by an objective function using a quadratic formula of qubit variables. The problem of an Ising model aims to determine the qubit values of the variables that minimize the objective function, and many optimization problems can be reduced to this problem. In this paper, we focus on optimization problems related to permutations, where the goal is to find the optimal permutation out of the $n!$ possible permutations of $n$ elements. To represent these problems as Ising models, a commonly employed approach is to use a kernel that utilizes one-hot encoding to find any one of the $n!$ permutations as the optimal solution. However, this kernel contains a large number of quadratic terms and high absolute coefficient values. The main contribution of this paper is the introduction of a novel permutation encoding technique called dual-matrix domain-wall, which significantly reduces the number of quadratic terms and the maximum absolute coefficient values in the kernel. Surprisingly, our dual-matrix domain-wall encoding reduces the quadratic term count and maximum absolute coefficient values from $n^3-n^2$ and $2n-4$ to $6n^2-12n+4$ and $2$, respectively. We also demonstrate the applicability of our encoding technique to partial permutations and Quadratic Unconstrained Binary Optimization (QUBO) models. Furthermore, we discuss a family of permutation problems that can be efficiently implemented using Ising/QUBO models with our dual-matrix domain-wall encoding.Comment: 26 pages, 9 figure

Resminostat in EGFR-mutated lung cancer

Drug-tolerant cells are mediators of acquired resistance. BIM-intron2 deletion polymorphism (BIM-del) is one of the mechanisms underlying the resistance to epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI)-mediated apoptosis that induces drug tolerance. Here, we investigated whether resminostat, a histone deacetylase inhibitor, circumvents BIM-del-associated apoptosis resistance. The human EGFR-mutated non-small cell lung cancer (NSCLC) cell line PC-9 and its homozygous BIM-del-positive variant (PC-9 BIMi2-/-), established by editing with zinc finger nuclease, were used. In comparison with PC-9 cells, PC-9 BIMi2-/- cells were less sensitive to apoptosis mediated by EGFR-TKIs such as gefitinib and osimertinib. The combined use of resminostat and an EGFR-TKI preferentially induced the expression of the pro-apoptotic BIM transcript containing exon 4 rather than that containing exon 3, increased the level of pro-apoptotic BIM protein (BIMEL), and stimulated apoptosis in vitro. In a subcutaneous tumor model derived from PC-9 BIMi2-/- cells, gefitinib monotherapy decreased tumor size but retained residual lesions, indicative of the presence of tolerant cells in tumors. The combined use of resminostat and gefitinib increased BIMEL protein level and induced apoptosis, subsequently leading to the remarkable shrinkage of tumor. These findings suggest the potential of resminostat to circumvent tolerance to EGFR-TKIs associated with BIM deletion polymorphism

Extreme hyperglycemia and diabetic ketoacidosis occurring in a patient on chronic dialysis

Department of Urology, North medical center, Kyoto prefectural university of medicine, Kyoto, Japan.Department of Nephrology and Urology, Nishijin Hospital, Kyoto, Japan.Department of Internal medicine, Nishijin Hospital, Kyoto, Japan.Diabetic ketoacidosis (DKA) is a complication that is rarely reported in patients on chronic dialysis. Herein, we describe the case of a patient on chronic hemodialysis who presented to us with acute onset diabetic ketoacidosis. A 50-year-old man with insulin-dependent diabetes mellitus, who was on hemodialysis for 2 years, presented to us with altered consciousness. Laboratory data revealed the following results: blood sugar, 110.1 mmol/L (1984 mg/dL); serum sodium, 107 mmol/L; β -hydroxybutyric acid, 1991 μ M; pH, 7.048. A diagnosis of diabetic ketoacidosis was made, and insulin therapy and hemodialysis were initiated, following which his parameters including blood glucose, and serum potassium and sodium improved. High osmotic dehydration was not observed in our patient owing to his renal dysfunction. The patient’s consciousness normalized following the correction of hyperglycemia and DKA. This case report highlights the importance of early diagnosis of DKA, and prompt initiation of insulin therapy and hemodialysis in patients on chronic dialysis. Therefore, in patients with end stage renal disease, the blood glucose correction should be followed by the restoration of sodium and osmolality, guided by corrected sodium concentration and effective osmolality, and by the appropriate adjustment of insulin and dialysis

Serum and urinary ferritin levels in patients with rheumatoid arthritis

The serum and urinary ferritin levels in 52 RA patients were measured by the 2-site immunoradiometric assay method. Serum ferritin levels in RA patients correlated with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) but not with serum iron levels and hemoglobin concentrations, although they were within the normal range. High serum ferritin levels were associated with sera with hyper gamma-globulin and rheumatoid factors. In sequential studies, serum ferritin changed in parallel with ESR, CRP and disease activity in a majority of the patients. The urinary ferritin levels and u/s ratios in some RA patients were higher than control values. Higher values were found particularly in the group of patients under gold therapy but not in groups under other treatments.</p

Genetics of symbiosis in Lotus japonicus: Recombinant inbred lines, comparative genetic maps, and map position of 35 symbiotic loci

Development of molecular tools for the analysis of the plant genetic contribution to rhizobial and mycorrhizal symbiosis has provided major advances in our understanding of plant-microbe interactions, and several key symbiotic genes have been identified and characterized. In order to increase the efficiency of genetic analysis in the model legume Lotus japonicus, we present here a selection of improved genetic tools. The two genetic linkage maps previously developed from an interspecific cross between L. japonicus Gifu and L. filicaulis, and an intraspecific cross between the two ecotypes L. japonicus Gifu and L. japonicus MG-20, were aligned through a set of anchor markers. Regions of linkage groups, where genetic resolution is obtained preferentially using one or the other parental combination, are highlighted. Additional genetic resolution and stabilized mapping populations were obtained in recombinant inbred lines derived by a single seed descent from the two populations. For faster mapping of new loci, a selection of reliable markers spread over the chromosome arms provides a common framework for more efficient identification of new alleles and new symbiotic loci among uncharacterized mutant lines. Combining resources from the Lotus community, map positions of a large collection of symbiotic loci are provided together with alleles and closely linked molecular markers. Altogether, this establishes a common genetic resource for Lotus spp. A web-based version will enable this resource to be curated and updated regularly.European Union HPRN-CT-2000-00086, MRTN-CT-2003-505227National Sciences and Engineering Research Council 3277A01Ministerio de Educación y Ciencia BFU2005-0312