Functional polymorphisms of HSPA5: possible association with bipolar disorder

Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of HSPA5 may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder.     

Beyond vasodilation: the antioxidant effect of adrenomedullin in Dahl salt-sensitive rat aorta

We have investigated the antioxidant effect of adrenomedullin (AM) on endothelial function in the Dahl salt-sensitive (DS) rat hypertension model. Dahl salt-resistant (DR) and DS rats were fed an 8% NaCl diet. In addition, the DS rats were subcutaneously infused with either saline or recombinant human AM for 4 weeks. Although systolic blood pressures measured weekly in AM- and saline-infused rats did not significantly differ, aortic O2*- levels were significantly (P<0.01) higher in the latter. Likewise, both endothelial nitric oxide synthase (eNOS) mRNA and protein were significantly higher in saline-infused DS rats. Infusion of AM reduced both O2*- and eNOS expression to levels comparable to those seen in DR rats. AM infusion also upregulated the gene expression of guanosine-5'-triphosphate cyclohydrolase I and downregulated the expression of p22(phox), suggesting that AM increased the NOS coupling and bioavailability of NO. AM possesses significant antioxidant properties that improve endothelial function.     

Role of microtubules and centrosomes in the eccentric relocation of the germinal vesicle upon meiosis reinitiation in sea-cucumber oocytes

In the oocytes of many animals, the germinal vesicle (GV) relocates from the center to the periphery of the oocyte upon meiosis reinitiation, which is a prerequisite to the formation of meiotic spindles beneath the cell surface in order for meiosis to succeed. In the present study, we have investigated nuclear positioning using sea-cucumber oocytes. Upon meiosis reinitiation, the GV relocates to the cell periphery beneath a surface protuberance. After GV breakdown, polar bodies were extruded from the top of the protuberance, which we therefore called the animal pole process. The GV relocation was inhibited by nocodazole but not by cytochalasin. Immunofluorescent staining and electron microscopy of microtubular arrays revealed that: (i) in immature oocytes, two centrosomes were situated beneath the animal pole process far apart from the GV, anchoring to the cortex via astral microtubules; (ii) upon meiosis reinitiation, microtubular bundles were newly formed between the centrosomes and the GV; and (iii) the microtubular bundles became short as GV migration proceeded. These observations suggest that microtubules and centrosomes participate in GV relocation. A very large mass of annulate lamellae, having a 20-microm diameter, was found in the vegetal pole of the oocytes.     

Preparation of aliphatic poly(thioester) by the lipase-catalyzed direct polycondensation of 11-mercaptoundecanoic acid

An aliphatic polythioester was enzymatically prepared by the direct polycondensation of mercaptoalkanoic acid using immobilized lipase of Candida antarctica (lipase CA) in bulk. The commercially available 11-mercaptoundecanoic acid was polymerized by lipase CA in bulk in the presence of molecular sieves 4A as a water absorbent at 110 degrees C for 48 h to produce poly(11-mercaptoundecanoate) with an M(w) of 34 000 in high yield. The 104.5 degrees C melting temperature (T(m)) of poly(11-mercaptoundecanoate) was about 20 degrees C higher than that of the corresponding polyoxyester, poly(11-hydroxyundecanoate). The polythioester was readily transformed by lipase into the corresponding cyclic oligomers mainly consisting of the dimer, which were readily repolymerized by the ring-opening polymerization using lipase as a sustainable chemical recycling.     

Maintenance of meiotic arrest and developmental potential of porcine oocytes after parthenogenetic activation and somatic cell nuclear transfer

Several studies report that meiotic maturation of porcine oocytes can be reversibly preserved. The present study examined how long meiotic maturation can be suppressed. The first experiment determined the preservation medium suitable for reversibly suppressing meiotic maturation of porcine oocytes. The second experiment examined the in vitro developmental potential of oocytes maintained in meiotic arrest after parthenogenetic activation and nuclear transfer of somatic cells. Preservation of cumulus-oocyte complexes with NCSU-37 medium containing 10% follicular fluid, 1 mM dibutyryl cyclic AMP, and follicular shell pieces for 24-96 h at 39 degrees C did not affect oocyte maturation compared with controls (94-98% vs. 98%). The potential of parthenogenetically activated and nuclear-transferred oocytes maintained in meiotic arrest for 24-48 h to develop into blastocysts was not significantly different from that of controls (20-25% vs. 18% and 8-11% vs. 9%, respectively). The present study demonstrated that meiotic maturation of porcine oocytes can be suppressed after preservation for 48 h at 39 degrees C without decreasing oocyte maturation competence or the ability of oocytes to develop to at least the blastocyst stage.     

Preparation and supramolecular properties of unadulterated glycosyl liposomes from a bis(alpha-D-mannopyranosyl)-[60]fullerene conjugate

The bis(alpha-D-mannopyranosyl)-[60]fullerene conjugate 3 was prepared by thermal coupling of C60 and either 2-azidoethyl 2,3,4,6-tetra-O-acetyl- or 2,3;4,6-di-O-isopropylidene-alpha-D-mannopyranoside (Scheme). Compound 3 was found to readily self-assemble. Dynamic-light-scattering (DLS) and atomic-force microscopy (AFM) experiments supported that the amphiphilic compound gives rise to nano-sized supramolecular structures during sugar deprotection (Ac-group removal) performed in MeOH/CH2Cl2 solution. Encapsulation studies with an aqueous suspension of 3 showed that the self-assembling structure envelopes Ba2+ and the fluorescent dye Acridine Red during its formation, which indicates that it resembles a bilayer vesicle or an unadulterated liposome with an inner hollow space. In addition to this notable property, the unique molecular geometry of the spatially arranged mannosyl surface residues of 3 gives rise to strong binding of the carbohydrate-recognizing lectin Con A. Hence, the polar amphiphilic end of 3 mimics the structure of 3,6-branched tri-alpha-D-mannoside (6; Fig. 3), a natural ligand of the Con A protein.     

<Emphasis Type="Italic">OsMADS22</Emphasis>, an <Emphasis Type="Italic">STMADS11</Emphasis>-like MADS-box gene of rice,is expressed in non-vegetative tissues and its ectopic expression induces spikelet meristem indeterminacy

We report the cDNA sequence and gene expression patterns of OsMADS22, a novel member of the STMADS11-like family of MADS-box genes, from rice. In contrast to previously reported STMADS11-like genes, whose expression is detected in vegetative tissues, OsMADS22 is mainly expressed during embryogenesis and flower development. In situ hybridization analysis revealed that OsMADS22 expression is localized in the L1 layer of embryos and in developing stamen primordia. Ectopic expression of OsMADS22 in transgenic rice plants resulted in aberrant floral morphogenesis, characterized by a disorganized palea, an elongated glume, and a two-floret spikelet. The results are discussed in terms of rice spikelet development and a novel non-vegetative role for a STMADS11-like gene.