Construction of the ACDE Ring System of Calyciphylline A-type Alkaloids via Intramolecular Diels-Alder Reaction of a Tetrasubstituted Olefin

A concise synthesis of the ACDE tetracyclic ring system of calyciphylline A-type alkaloids was investigated. The intramolecular Diels–Alder reaction of a tetrasubstituted olefin with furan enabled the construction of the ACD ring system bearing two contiguous quaternary carbons in one step, and subsequent intramolecular [3+2] cycloaddition successfully gave the E ring

Tsunami Evacuation Simulation Considering Building Collapse and Fire Spread

The objective of this study is to develop a tsunami evacuation simulation system that takes into account building collapse and fire spread. Road blockage is determined by calculating the road blockage probability due to building collapse, taking into account the size of the assumed earthquake, location of buildings, and type of building. For fire spread simulation, an existing simulator based on the fire spread rate equation is used. Under average wind direction and speed conditions for the target area, arbitrary fire points are set up and fire spread is represented using fire times for each building obtained from the simulation. The applicability of this system as a scenario is extended. The present system is applied to several examples to demonstrate the validity and effectiveness of the system

統合失調症患者が地域生活において対処できない問題とその対処に向けた訪問看護師の支援

目的:統合失調症患者が地域生活において対処できない問題とその対処に向けた訪問看護師の支援を明らかにする.方法:A県内の精神科病院および訪問看護ステーションにおいて統合失調症患者を支援している訪問看護師を対象として面接調査を行い,Berelson,B.の内容分析を参考にして分析した.結果:訪問看護師が語った統合失調症患者が地域生活において対処できない問題は,【服薬自己管理ができないため薬を正しく飲めない】【入浴・洗髪・行為をできないため清潔が保てない】など11コアカテゴリが抽出された.統合失調症患者が地域生活において対処できない問題の対処に向けた訪問看護師の支援は,《服薬自己管理ができるように服薬確認や声かけを行う》など17コアカテゴリであった.結論:訪問看護師は,患者が地域生活において対処できない服薬,清潔,金銭管理,熱中症予防などの問題に対して,患者の状態に合わせて段階的に継続的な支援を行っていた.Purpose: To elucidate the problems in community living that patients with schizophrenia are unable to manage and the support provided by visiting nurses to address these problems. Methods : Interviews were conducted with visiting nurses caring for patients with schizophrenia at a psychiatric hospital or a visiting nurse service provider in Prefecture A. Interview data were analyzed according to Berelson's method of content analysis. Results : Results : Analysis of interview data extracted 11 core categories of problems in community living experienced by patients with schizophrenia, such as "medication errors due to inability to self-manage medication" and "cleanliness problems due to inability to bathe, shampoo and change clothing". The analysis also extracted 17 core categories of support that visiting nurses provided to address the problems, such as "checking medication and providing reminders to help patients manage self-medication." Conclusion : Visiting nurses provided continuous support to patients with schizophrenia living in the community in problem areas such as taking medication,cleanliness,money management and heat stroke prevention according to the condition of the patient.報

Targeted reversion of induced pluripotent stem cells from patients with human cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect model

BackgroundRunt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Here, we investigated whether induced pluripotent stem cells (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2 mutation in iPSCs derived from CCD patients to establish normal iPSCs, and whether engraftment of osteoblasts derived from properly reverted iPSCs results in better regeneration in immunodeficient rat calvarial bone defect models.MethodsTwo cases of CCD patient-derived induced pluripotent stem cells (CCD-iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using programmable nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs. The mRNA expressions of osteoblast-specific markers were analyzed using quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived osteoblasts were transplanted into rat calvarial bone defects, and bone regeneration was evaluated using microcomputed tomography analysis and histological analysis.ResultsMutation analysis showed that both contained nonsense mutations: one at the very beginning of exon 1 and the other at the initial position of the nuclear matrix-targeting signal. The osteoblasts derived from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast differentiation markers, and transplantation of these osteoblasts into calvarial bone defects created in rats with severe combined immunodeficiency showed poor regeneration. However, reverted iPSCs improved the abnormal osteoblast differentiation which resulted in much better engraftment into the rat calvarial bone defect.ConclusionsTaken together, these results demonstrate that patient-specific iPSC technology can not only provide a useful disease model to elucidate the role of RUNX2 in osteoblastic differentiation but also raises the tantalizing prospect that reverted iPSCs might provide a practical medical treatment for CCD

Real-Time PCR Assay for the Diagnosis and Quantification of Co-infections by Diaporthe batatas and Diaporthe destruens in Sweet Potato

Foot rot disease caused by Diaporthe destruens (formerly Plenodomus destruens) has become a major concern for the production of sweet potato [Ipomoea batatas (L.) Lam.] in Japan. A related fungus Diaporthe batatas, which causes dry rot disease of sweet potato, is native and is widespread in fields in Japan. The similar characteristics of these two pathogens pose a challenge for conventional disease diagnosis. Currently, there are no effective molecular measures for identifying and distinguishing D. destruens and D. batatas. Here, we demonstrate a real-time PCR assay that distinguishes and quantifies D. batatas and D. destruens from co-infected sweet potato. The assay was performed with various simulated DNA combinations of D. batatas and D. destruens ranging from 1:1 to 1:100000. The assay was also used with the ratios of D. batatas: D. destruens: sweet potato DNA ranging from 1:1:1 to 1:1:100000. These assays produced a specific amplification product for each of the pathogens, and quantified the fungal biomass over the entire range tested without detecting false positives. The assay was validated by using infected sweet potato collected from various fields; it showed sufficient sensitivity and specificity to quantify and distinguish D. batatas and D. destruens from these field samples. Thus, our real-time PCR assay would be a useful tool for diagnosis of D. batatas and D. destruens and is expected to provide the foundation for the design of integrated disease management strategies for foot rot disease in sweet potato

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Enhancement of Both Long-Term Depression Induction and Optokinetic Response Adaptation in Mice Lacking Delphilin

In the cerebellum, Delphilin is expressed selectively in Purkinje cells (PCs) and is localized exclusively at parallel fiber (PF) synapses, where it interacts with glutamate receptor (GluR) δ2 that is essential for long-term depression (LTD), motor learning and cerebellar wiring. Delphilin ablation exerted little effect on the synaptic localization of GluRδ2. There were no detectable abnormalities in cerebellar histology, PC cytology and PC synapse formation in contrast to GluRδ2 mutant mice. However, LTD induction was facilitated at PF-PC synapses in Delphilin mutant mice. Intracellular Ca2+ required for the induction of LTD appeared to be reduced in the mutant mice, while Ca2+ influx through voltage-gated Ca2+ channels and metabotropic GluR1-mediated slow synaptic response were similar between wild-type and mutant mice. We further showed that the gain-increase adaptation of the optokinetic response (OKR) was enhanced in the mutant mice. These findings are compatible with the idea that LTD induction at PF-PC synapses is a crucial rate-limiting step in OKR gain-increase adaptation, a simple form of motor learning. As exemplified in this study, enhancing synaptic plasticity at a specific synaptic site of a neural network is a useful approach to understanding the roles of multiple plasticity mechanisms at various cerebellar synapses in motor control and learning

Concise Construction of the ACDE Ring System of Calyciphylline A Type Alkaloids by a [5+2] Cycloaddition

A concise route for construction of the ACDE ring skeleton in calyciphylline A type alkaloids was developed using an intramolecular [5+2] cycloaddition reaction of an oxidopyrylium species bearing a tetrasubstituted olefin. Key to the success of this reaction was the combination of acid and base, which accelerated the construction of this skeleton containing a spiro ring and vicinal quaternary carbon centers. The resultant tricyclic ADE ring compound was converted to an ACDE ring model through C−H oxidation and an aza‐Wittig reaction