Four commercially available samples of bacterial poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] containing from 6.5 to 21.8 mol % 3HV have been fractionated by chloroform/reheptane mixed solvent. They have been separated into several fractions with wide composition ranges. These results show that the composition distribution of as received bacterial P(3HB-co-3HV)s is extremely broad and/or has many peaks over a wide composition range. The effects of the complex composition distribution on physical properties have been analyzed through the comparison of melting and crystallization behavior between samples before and after fractionation. Three as received P(3HB-co-3HV)s show the behavior corresponding to the average composition in spite of their complex composition distribution. The melting temperature and spherulite growth rate correspond to the values expected from extrapolation of the data from the fractionated samples. In these copolyesters, cocrystallization of the chains within the wide composition range occurs. However, one as received P(3HB-co-3HV) has a higher melting temperature and faster growth rate than might be expected. The apparent crystallization behavior corresponds to that of P(3HB-co-3HV) with lower 3HV content. These data suggest that only the component chains of relatively low 3HV content are crystallized in this as received P(3HB-co-3HV). The crystallization of components of high 3HV content is significantly restricted. The extremely broad composition distribution of this copolyester affects the crystallization (melting) behavior.
Purpose To determine the prevalence and risk factors of epiretinal membranes (ERM) in a Japanese population. Patients and Methods The Funagata Study examined 1758 Japanese aged 35 years or older (42% of eligible) from June 2000 to June 2002. A total of 1723 (98.0%) participants had nonmydriatic fundus photographs of the right eye to grade the presence of ERM, using the Blue Mountains Eye Study (BMES) protocol. After age standardization, the prevalence of ERM in the right eyes of the participants included in this study was compared with that reported from right eyes of participants in the BMES and the Beaver Dam Eye Study (BDES). ERM detected in eyes with diabetic retinopathy and other retinal lesions were excluded from the analysis of associations. Multiple logistic regression models were used to determine risk factors for the presence of ERM, adjusting for age and gender. Results There were 84 right eyes with ERM, representing 5.44% of this sample. After age standardization, the prevalence rate (5.7%) was within the range reported in the BMES (3.5%) and the BDES (6.9%). Older age (genderadjusted odds ratio (OR) per 10 years: 1.72, 95% confidence interval (CI): 1.40-2.11) and diabetes (age-gender-adjusted OR: 1.84, 95% CI: 1.01-3.37) were the only two factors associated with ERM. Conclusions We found a similar prevalence of ERM in the Japanese as in mainly white populations. Increasing age and diabetes were risk factors for ERM in this adult Japanese population.
This community-based longitudinal study found that increased ABP variability was associated with SVD progression, particularly in individuals with SVD at baseline. Higher systolic ARV predicted SVD progression and cognitive decline.
Hepatocyte nuclear factor 1beta (HNF1beta) abnormalities have been recognized to cause congenital anomalies of the kidney and urinary tract (CAKUT), predominantly affecting bilateral renal malformations. To further understand the spectrum of HNF1beta related phenotypes, we performed HNF1B gene mutation and deletion analyses in Japanese patients with renal hypodysplasia (n = 31), unilateral multicystic dysplastic kidney (MCDK; n = 14) and others (n = 5). We identified HNF1B alterations in 5 out of 50 patients (10%). De novo heterozygous complete deletions of HNF1B were found in 3 patients with unilateral MCDK. Two of the patients showed contralateral hypodysplasia, whereas the other patient showed a radiologically normal contralateral kidney with normal renal function. Copy number variation analyses showed 1.4 Mb microdeletions involving the whole HNF1B gene with breakpoints in flanking segmental duplications. We also identified 1 novel truncated mutation (1007insC) and another missense mutation (226G>T) in patients with bilateral hypodysplasia. HNF1B alterations leading to haploinsufficiency affect a diverse spectrum of CAKUT. The existence of a patient with unilateral MCDK with normal renal function might provide genetic insight into the etiology of these substantial populations of only unilateral MCDK. The recurrent microdeletions encompassing HNF1B could have a significant impact on the mechanism of HNF1B deletions.
ABSTRACT:Crystallization and melting behavior of blends of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(HBco-HV)) copolyesters, which were prepared by compositional fractionation of bacterially synthesized P(HB-co-HV) and have a narrow composition distribution, have been investigated and compared to those of P(HB-co-HV) before fractionation. Analysis of DSC melting thermograms and spherulite growth rate indicates four situations that might arise from the blend. These are: (i) An isomorphous crystalline phase being formed from the miscible melt. (ii) Two crystalline phases observed in situations (i) and (iii) being formed from the miscible melt. (iii) A crystalline phase of the component polyester having the largest crystallization rate being partitioned from the miscible melt. (iv) Two crystalline phase similar to the pure components being formed from the immiscible melt. Most bacterial P(HB-co-HV) copolyesters are in situation (i) and are indistinguishable from P(HB-co-HV) having a narrow composition distribution. Some bacterial P(HB-co-HV) copolyesters, which have a extremely broad composition distribution, show behavior different from P(HB-co-HV) with a narrow one. We need to take account of the details of composition distribution of these P(HB-co-HV) samples. Especially in situation (iii), we are apt to mistake the properties of the partitioned crystals for those of the isomorphous crystals. An observation of a single Tm is not sufficient to confirm the isomorphous crystals.KEY WORDS Composition Distribution / Polymer Blend / Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) / Recently, productions of various hydroxyalkanoate copolymers (PHAs) by bacterial fermentation have been reported. The importance of this family owes to biodegradability combined with thermoplasticity. Poly(3-hydroxybutyrate) (PHB) and its copolyesters with 3-hydroxyvalerate (PHB-HV) are the best-known members of this family. 1 -3 A variety of properties 4 · 5 such as melting temperature, 6 -8 solid-state structure, 6 • 9 -10 -12 crystallization behavior, 11 • 13 mechanical properties, 14 · 1 5 and enzymatic degradation processes, 16 have been studied for this copolyester. Most of the studies focused on the dependence of these properties on the comonomer composition. These properties certainly vary with the HV content. In these studies, however, a narrow composition distribution was expected without any careful consideration.Every copolymer is considered to be a kind of polymer blends by its nature, that is, a copolymer material is composed of molecules over a range of comonomer compositions. In general, the range in a synthesized copolymer is believed to be very narrow. We can treat a copolymer material as a mass of identical macromolecules and the average composition as a composition of every molecule. In this study, we refer to only the copolymer with a narrow composition distribution as a pure copolymer. However, we found recently that bacterial PHB-HV copolyesters have a complex feature of composition distribution, i.e., their compo...
In the purple membrane of Halobacterium salinarium, bacteriorhodopsin trimers are arranged in a hexagonal lattice. When purple membrane sheets are incubated at high temperature with neutral detergent, membrane vesicularization takes place, yielding inside-out vesicles with a diameter of 50 nm. The vesicular structure becomes unstable at low temperature, where successive fusion of the vesicles yields a crystal which is composed of stacked planar membranes. X-ray crystallographic analysis reveals that the bacteriorhodopsin trimers are arranged in a honeycomb lattice in each membrane layer and that neighbouring membranes orient in opposite directions. The native structure of the trimeric unit is preserved in the honeycomb lattice, irrespective of alterations in the in-plane orientation of the trimer. One phospholipid tightly bound to a crevice between monomers in the trimeric unit is suggested to act as a glue in the formation of the trimer.
Midnolin (MIDN) was first discovered in embryonic stem cells, but its physiological and pathological roles are, to date, poorly understood. In the present study, we therefore examined the role of MIDN in detail. We found that in PC12 cells, a model of neuronal cells, MIDN localized primarily to the nucleus and intracellular membranes. Nerve growth factor promoted MIDN gene expression, which was attenuated by specific inhibitors of extracellular signal-regulated kinases 1/2 and 5. MIDN-deficient PC12 cells created using CRISPR/Cas9 technology displayed significantly impaired neurite outgrowth. Interestingly, a genetic approach revealed that 10.5% of patients with sporadic Parkinson’s disease (PD) had a lower MIDN gene copy number whereas no copy number variation was observed in healthy people, suggesting that MIDN is involved in PD pathogenesis. Furthermore, the expression of parkin, a major causative gene in PD, was significantly reduced by CRISPR/Cas9 knockout and siRNA knockdown of MIDN. Activating transcription factor 4 (ATF4) was also down-regulated, which binds to the cAMP response element (CRE) in the parkin core promoter region. The activity of CRE was reduced following MIDN loss. Overall, our data suggests that MIDN promotes the expression of parkin E3 ubiquitin ligase, and that MIDN loss can trigger PD-related pathogenic mechanisms.
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