Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders

Elucidating the neural and genetic factors underlying psychiatric illness is hampered by current methods of clinical diagnosis. The identification and investigation of clinical endophenotypes may be one solution, but represents a considerable challenge in human subjects. Here we report that mice heterozygous for a null mutation of the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha-CaMKII+/-) have profoundly dysregulated behaviours and impaired neuronal development in the dentate gyrus (DG). The behavioral abnormalities include a severe working memory deficit and an exaggerated infradian rhythm, which are similar to symptoms seen in schizophrenia, bipolar mood disorder and other psychiatric disorders. Transcriptome analysis of the hippocampus of these mutants revealed that the expression levels of more than 2000 genes were significantly changed. Strikingly, among the 20 most downregulated genes, 5 had highly selective expression in the DG. Whereas BrdU incorporated cells in the mutant mouse DG was increased by more than 50 percent, the number of mature neurons in the DG was dramatically decreased. Morphological and physiological features of the DG neurons in the mutants were strikingly similar to those of immature DG neurons in normal rodents. Moreover, c-Fos expression in the DG after electric footshock was almost completely and selectively abolished in the mutants. Statistical clustering of human post-mortem brains using 10 genes differentially-expressed in the mutant mice were used to classify individuals into two clusters, one of which contained 16 of 18 schizophrenic patients. Nearly half of the differentially-expressed probes in the schizophrenia-enriched cluster encoded genes that are involved in neurogenesis or in neuronal migration/maturation, including calbindin, a marker for mature DG neurons. Based on these results, we propose that an "immature DG" in adulthood might induce alterations in behavior and serve as a promising candidate endophenotype of schizophrenia and other human psychiatric disorders

トウニョウビョウ ケア ノ リスク マネージメント

The number of diabetics has been increasing in recent years. The diabetics are under varioustreatments, including the improvement of life habit and the medication for diabetes with insulin.Our hospital set a team of diabetic care, which is composed of a diabetic specialist, certified diabeteseducators（CDEs）, nurses, dietricians and pharmacists. This team takes great care of the diabetics.For medical safety measures, the department of risk management was organized in our hospital.The department investigated the cases of Hiyari-Hatto within 1 year and 3 months, from 2005to 2006, and found that 3% of them was the diabetic case, which was caused by the nurses exceptCDEs. Therefore the department made the manual of diabetic therapy in cooperation with theCDEs. All the staffs in our hospital were educated by the seminars according to the manual. Theknowledge about the diabetic therapy proved to be mostly accurate one year after the last seminar.For the improvement of medical safety, the department of risk management helps the CDEswith holding the educational seminars by giving the informations after analyzing the cases of Hiyari-Hatto and the questionnaires following the seminars

Demand for family planning satisfied with modern methods and its associated factors among married women of reproductive age in rural Jordan: A cross-sectional study.

BACKGROUND:A novel indicator, 'percentage of women of reproductive age who are sexually active and who have their demands for FP satisfied with modern contraceptive methods (mDFPS)', was developed in 2012 to accelerate the reduction of unmet needs of family planning (FP). In Jordan, unmet needs for modern contraception remain high. To address this situation, this study measured the mDFPS and identified its associated factors in rural Jordan. METHODS:This cross-sectional study included married women of reproductive age (15-49 years) from ten villages in Irbid Governorate, Jordan, where advanced health facilities are difficult to reach. A two-stage stratified sampling with random sampling at the household stage was used for this field survey which was conducted between September and October 2016. Univariate analysis was used to assess the differences between mDFPS and unmet mDFPS groups. Logistic regression analysis was performed to identify the correlates of mDFPS. RESULTS:Of 1019 participants, 762 were identified as needing modern contraception. mDFPS coverage accounted for 54.7%. The most significant factors associated with mDFPS were the husband's agreement on FP (adjusted odds ratio [AOR]: 15.43, 95% confidence interval [CI]: 5.26-45.25), knowledge of modern contraceptives (AOR: 8.76, 95% CI: 5.72-13.40), and lack of awareness of the high risk of conception in the postpartum period (AOR: 2.21, 95% CI: 1.41-3.47). Duration of current residence, receipt of FP counselling at health centres and number of living children were also correlated. In addition, 95.3% of local women were aware of the presence of health centres that were mostly located in a 10-minute walking distance. CONCLUSION:To increase mDFPS, this study suggested that accelerating male involvement in FP decision-making is necessary through community-based health education. Furthermore, expanding FP services in village health centres and improving the quality of FP counselling in public health facilities are required to correct misconceptions about modern methods among rural women

Cupin Variants as Macromolecular Ligand Library for Stereoselective Michael Addition of Nitroalkanes

Cupin superfamily proteins (TM1459) work as a macromolecular ligand framework with a double-stranded beta-barrel structure ligating to a Cu ion through histidine side chains. Variegating the first coordination sphere of TM1459 revealed that H52A and H54A/H58A mutants effectively catalyzed the diastereo- and enantio-selective Michael addition reaction of nitroalkanes to an α,β-unsaturated ketone. Moreover, in silico substrate docking signified C106N and F104W single-point mutations, which inverted the diastereoselectivity of H52A and further improved the stereoselectivity of H54A/H58A, respectively

An Artificial Metallolyase with Pliable 2-His-1-Carboxylate Facial Triad for Stereoselective Michael Addition

We repurposed the metal-binding site of a cupin superfamily protein into the 2-his-1-carboxylate facial triad, which is one of the common motifs in natural non-heme enzymes, to construct artificial metalloenzymes that can catalyze new-to-nature reactions. Cu2+-H52A/H58E variant catalyzed the stereoselective Michael addition reaction and was found to bear a flexible metal-binding site in the high-resolution crystal structure. Furthermore, the H52A/H58E/F104W mutant accommodated a water molecule, which was supported by Glu58 and Trp104 residues via hydrogen bonding, presumably leading to high stereoselectivity. Thus, the 2-his-1-carboxylate facial triad was confirmed to be a versatile and promising metal-binding motif for abiological and canonical biological reactions

Synthesis and Properties of Polycarbosilanes Having 5‑Membered Cyclic Carbonate Groups as Solid Polymer Electrolytes

We conducted ring-opening polymerization of silacyclobutane monomers 1-[2-(2,4-dioxa-3-pentanoyl)­ethyl]-1-methylsilacyclobutane (SBMC) and 1,1-di­[2-(2,4-dioxa-3-pentanoyl)­ethyl]­silacyclobutane (SBDC) to obtain polySBMC and polySBDC, respectively, and measured their ionic conductivity with addition of lithium bis­(trifluoromethanesulfonyl)­imide (LiTFSI) or lithium trifluoromethanesulfonate (LiOTf). The ionic conductivity of both polySBMC and polySBDC increased with the increase in the amount of LiTFSI added. The ionic conductivity of polySBMC decreased with the increase in the amount of LiTOf, and that of polySBDC decreased after an increase. PolySBMC and polySBDC showed ionic conductivity of 6.1 × 10^–5 and 1.5 × 10^–4 S/cm at 30 °C, respectively, after the addition of 4 mol equiv of LiTFSI per cyclic carbonate. Differential scanning calorimetry analysis of the polymer revealed that the polymers with a high LiTFSI content formed a crystalline phase around room temperature, but the glass transition temperatures of the amorphous phases were kept low. Infrared analysis suggested the existence of a strong interaction between carbonate carbonyl groups and lithium cations