A connecter-like factor, CacA, links RssB/RpoS and the CpxR/CpxA two-component system in Salmonella

BACKGROUND: Bacteria integrate numerous environmental stimuli when generating cellular responses. Increasing numbers of examples describe how one two-component system (TCS) responds to signals detected by the sensor of another TCS. However, the molecular mechanisms underlying this phenomenon remain poorly defined. RESULTS: Here, we report a connector-like factor that affects the activity of the CpxR/CpxA two-component system in Salmonella enterica serovar Typhimurium. We isolated a clone that induced the expression of a cpxP-lac gene fusion from a high-copy-number plasmid pool of random Salmonella genomic fragments. A 63-amino acid protein, CacA, was responsible for the CpxA/CpxR-dependent activation of the cpxP gene. The CpxR-activated genes cpxP and spy exhibited approximately 30% and 50% reductions in transcription, respectively, in a clean cacA deletion mutant strain in comparison to wild-type. From 33 response regulator (RR) deletion mutants, we identified that the RssB regulator represses cacA transcription. Substitution mutations in a conserved -10 region harboring the RNA polymerase recognition sequence, which is well conserved with a known RpoS -10 region consensus sequence, rendered the cacA promoter RpoS-independent. The CacA-mediated induction of cpxP transcription was affected in a trxA deletion mutant, which encodes thioredoxin 1, suggesting a role for cysteine thiol-disulfide exchange(s) in CacA-dependent Cpx activation. CONCLUSIONS: We identified CacA as an activator of the CpxR/CpxA system in the plasmid clone. We propose that CacA may integrate the regulatory status of RssB/RpoS into the CpxR/CpxA system. Future investigations are necessary to thoroughly elucidate how CacA activates the CpxR/CpxA system

Trisomy 9 Mosaicism Diagnosed In Utero

We present three cases of trisomy 9 mosaicism diagnosed by amniocentesis with ongoing pregnancies after referral to our center due to fetal abnormalities. Two cases were associated with severe fetal growth restriction (FGR), each of which resulted in an intrauterine fetal demise (IUFD) in the third trimester. The other case involved mild FGR with a congenital diaphragmatic hernia and resulted in a live birth with severe development delay. A major prenatal finding of trisomy 9 mosaicism is FGR. Fetuses with trisomy 9 mosaicism can rarely survive in the case of severe FGR

Retrovirus Entry by Endocytosis and Cathepsin Proteases

Retroviruses include infectious agents inducing severe diseases in humans and animals. In addition, retroviruses are widely used as tools to transfer genes of interest to target cells. Understanding the entry mechanism of retroviruses contributes to developments of novel therapeutic approaches against retrovirus-induced diseases and efficient exploitation of retroviral vectors. Entry of enveloped viruses into host cell cytoplasm is achieved by fusion between the viral envelope and host cell membranes at either the cell surface or intracellular vesicles. Many animal retroviruses enter host cells through endosomes and require endosome acidification. Ecotropic murine leukemia virus entry requires cathepsin proteases activated by the endosome acidification. CD4-dependent human immunodeficiency virus (HIV) infection is thought to occur via endosomes, but endosome acidification is not necessary for the entry whereas entry of CD4-independent HIVs, which are thought to be prototypes of CD4-dependent viruses, is low pH dependent. There are several controversial results on the retroviral entry pathways. Because endocytosis and endosome acidification are complicatedly controlled by cellular mechanisms, the retrovirus entry pathways may be different in different cell lines

The effect of acotiamide on epigastric pain syndrome and postprandial distress syndrome in patients with functional dyspepsia

The effect of acotiamide on gastrointestinal symptoms is undefined. The aim of this study is to evaluate the effect of acotiamide on abdominal symptoms in patients with functional dyspepsia. We retrospectively reviewed 51 patients treated with acotiamide. We evaluated patient quality of life using the Izumo scale that detects changes in quality of life caused by abdominal symptoms. Acotiamide ameliorated the symptoms of functional dyspepsia at one and three months (improved : 61% vs 80%, p=0.029 and resolved : 17% vs 33%, p=0.069). We then evaluated the effect of acotiamide on epigastric pain syndrome (EPS) (n=33) and postprandial distress syndrome (PDS) (n=41). Acotiamide treatment showed an early effect on rates of improvement (63%) and resolution (42%) of EPS symptoms at one month, maintained up to three months (69% and 39%, respectively). Both rates of improvement and resolution of PDS symptoms showed a significant increase from one month to three months (56% vs 78%, p=0.021 and 17% vs 46%, p=0.004, respectively). The severity of functional dyspepsia symptoms before treatment was significantly associated with failed resolution of functional dyspepsia symptoms (p=0.013). Acotiamide improves and resolves EPS symptoms as well as PDS symptoms. PDS symptoms take longer to resolve than EPS symptoms

Clinical Study of the Efficacy and Safety of Liposomal Amphotericin B for the Treatment of Fungal Infections in Non-neutropenic Patients

Liposomal amphotericin B (L-AMB) is reported in Japan to be less effective and not as safe for treating severe fungal infections in non-neutropenic patients as in neutropenic patients. Therefore, we evaluated the clinical efficacy and safety of L-AMB as an antifungal agent in non-neutropenic patients. The efficacy of L-AMB administered intravenously in patients with severe fungal infections was retrospectively investigated by reviewing medical records from November 2007 to July 2010. The records of 18 eligible adult patients were analyzed according to the L-AMB dose they received: standard (2.5mg/kg/day; n=5) and high (>2.5mg/kg/day; n=13). The average age of the standard- and high-dosage group was 71.4 and 60.3 years, respectively. The 30-day survival rate in the standard- and high-dosage group was 20% (n=1) and 76.9% (n=10), respectively (P=0.047). A significant antipyretic effect was observed in the high-dosage group (P=0.001). There was no relationship between the dosage of L-AMB and any side effect. By carrying out the treatment according to the information provided at the time of administration, no cases were discontinued because of side effects. A high dosage of L-AMB is more effective than the standard dosage and both dosages are well-tolerated in non-neutropenic patients

Advanced Treatment and Imaging in Colonoscopy: The Pocket-Creation Method for Complete Resection and Linked Color Imaging for Better Detection of Early Neoplastic Lesions by Colonoscopy

Early detection and resection of neoplastic lesions are key objectives to diminish colorectal cancer mortality. Resection of superficial colorectal neoplasms, cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection have all been developed and used worldwide. The pocket-creation method facilitates the resection of tumors in difficult and routine locations. Early detection is the most important first step to maximize the benefits of recent advancements in endoscopic techniques. However, the detection of small, flat-shaped, or faded color lesions remains difficult. Linked color imaging, a novel multi-light technology, facilitates the recognition of minor differences in tissue by enhancing the color contrast between early colorectal neoplasms and surrounding normal mucosa in a bright field of view. The most striking feature of linked color imaging is its ability to display the color of early neoplastic lesions as distinct from inflammatory changes, both of which have similar “redness” when viewed using white light imaging. To increase the detection rate of neoplasms, linked color imaging should be used from the outset for endoscopic observation. Early detection of superficial colorectal tumors can result in decreased mortality from colorectal cancer and maintain a good quality of life for patients

学習管理システムの組織的な利活用のための教員の意識調査

学習管理システム(LMS)の全学的な利活用を進めている大学において，全教員を対象として実施したアンケート調査の結果について分析する．LMSを用いた教育の改善や効率化の組織的な取り組みが進められているが，利用者である教員の意識が必ずしも明らかにされているとはいえない．本稿では，2006年度からLMSを全学の教育基盤システムとして運用している理工系の大学を対象として，授業資料の公開に利用している教員，課題回収やオンラインテストなどの実施に活用している教員と，LMSを利用していない教員とを比較した．教員の利活用の状況および目的，今後利活用したい機能と課題に関する意識の違いを明らかにした