Network-Level Structural Abnormalities of Cerebral Cortex in Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) usually begins in childhood and adolescence and causes lifelong damage to several major organs including the brain. Despite increasing evidence of T1DM-induced structural deficits in cortical regions implicated in higher cognitive and emotional functions, little is known whether and how the structural connectivity between these regions is altered in the T1DM brain. Using inter-regional covariance of cortical thickness measurements from high-resolution T1-weighted magnetic resonance data, we examined the topological organizations of cortical structural networks in 81 T1DM patients and 38 healthy subjects. We found a relative absence of hierarchically high-level hubs in the prefrontal lobe of T1DM patients, which suggests ineffective top-down control of the prefrontal cortex in T1DM. Furthermore, inter-network connections between the strategic/executive control system and systems subserving other cortical functions including language and mnemonic/emotional processing were also less integrated in T1DM patients than in healthy individuals. The current results provide structural evidence for T1DM-related dysfunctional cortical organization, which specifically underlie the top-down cognitive control of language, memory, and emotion. © 2013 Lyoo et al

Seed-layer mediated orientation evolution in dielectric Bi-Zn-Ti-Nb-O thin films

Highly (hhh) -oriented pyrochlore Bi-Zn-Ti-Nb-O (BZTN) thin films were fabricated via metal-organic decomposition using orientation template layers. The preferred orientation was ascribed to the interfacial layer, the lattice parameter of which is similar to BZTN. High-resolution transmission electron microscopy supported that the interfacial layer consists of Bi and Pt. The (hhh) -oriented thin films exhibited a highly insulating nature enabling feasible applications in electronic devices, particularly voltage tunable application. The BZTN thin films did not show any apparent dielectric anisotropy and the slightly enhanced dielectric properties were discussed in connection to the internal stress and the grain boundary effect. © 2007 American Institute of Physics

Severity of Nonalcoholic Fatty Liver Disease is Associated with Development of Metabolic Syndrome: Results of a 5-Year Cohort Study

Aims: Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome (MS). However, a few studies have examined the effect of NAFLD on the development of MS. We evaluated the relationship between the development of MS and clinical severity of NAFLD according to alanine aminotransferase (ALT) levels. Methods: A retrospective cohort study was conducted. Participants who underwent abdominal ultrasonography and blood samplings for health check-ups both in 2005 and 2010 were recruited. NAFLD was diagnosed if a person showed fatty liver on ultrasonography without significant alcohol consumption. Subjects with MS at baseline were excluded. Results: A total of 2,728 subjects met the inclusion criteria. Fatty liver (FL) with normal ALT was found in 369 (13.5%) subjects and FL with elevated ALT in 328 (12.0%). During 5 years of follow up, 582 (21.3%) incident cases of MS developed between 2005 and 2010. The incidence of MS was higher in patients with NAFLD compared to control group (41.2% in FL with elevated ALT, 34.7% in FL with normal ALT and 15.7% in control, p<0.001). Multivariate analysis showed that odds ratio (OR) and 95% confidence interval (CI) for MS increased according to the severity of NAFLD [OR (95% CI), 1.29 (0.97−1.71) in FL with normal ALT and 1.54 (1.18−1.33) in FL with elevated ALT, p=0.01]. Conclusions: We have demonstrated that development of MS is significantly increased according to the clinical severity of NAFLD. These findings have implications in the clinical availability of NAFLD as a predictor of MS

High frequency plant regeneration from mature seedderived callus of Italian ryegrass (Lolium multiflorum) cultivars

In the present study, we have developed a high-frequency plant regeneration system for Italian ryegrass via callus culture using mature seeds as explants. Optimal embryogenic callus induction was found to occur in MS medium containing 5 mg l-1 2,4-D, 0.5 mg l-1 BA, 500 mg l-1 L-proline, 1 g l-1 casein hydrolysate, 30 g l-1 sucrose, 7 mg l-1 AgNO3, 2 mg l-1 CuSO4 and solidified with 3 g l-1 Gelrite. The highest regeneration rate was obtained in MS medium containing 1 mg l-1 2,4-D, 5 mg l-1 BA, 500 mg l-1 L-proline, 1 g l-1 casein hydrolysate, 1 mg l-1 thiamine-HCl, 30 g l-1 sucrose, 7 mg l-1 AgNO3, 2 mg l-1 CuSO4 and solidified with 3 g l-1 Gelrite. By using the most effective treatment determined for each parameter, the highest rates of embryogenic callus formation (48.9%) and regeneration (47.6%) were obtained with the Hwasan 101 cultivar. The overall plant regeneration rates of the examined cultivars ranged from 7.5 to 23.2%. Thus, optimization of regeneration frequency using mature seeds as explant material may offer a simple and efficient protocol for Italian ryegrass that may improve molecular breeding of this species

Molecular and genetic characterization of OSH6 (Oryza sativa Homeobox 6) using dissociation (Ds) insertion mutant rice

Genetic studies of dissociation (Ds) insertion mutant rice plants indicated that ectopic expression of truncated OSH6 (Oryza sativa Homeobox 6) mRNA may be responsible for the mutant phenotype of knotted leaf formation at the peduncle. Additionally, ectopic expression of truncated OSH6 mRNA in the OSH6-Ds mutant plant led to alteration of other homeobox genes including OSH15 in leaf tissues. The OSH6-Ds mutant plant exhibited altered expression of more than 118 genes on a 22K rice microarray in comparison with wild type plants. Of these genes, 20 were up- or down-regulated in both OSH6-Ds and OSH6-overexpressing (OSH6-35S) plants. Especially, OsDof3 was not expressed in floral organs, but was present in the panicles of both OSH6-Ds and OSH6-35S plants. It is assumed that truncated OSH6 transcript might be actively involved in the gene expression during organ development. The genetic relationship between OSH6-Ds and OSH15 suggested that the formation of the extra leaf is independent of OSH6-Ds or OSH15 expression. These results suggest that truncated OSH6 mRNA influences lateral organ growth and development by regulating the expression of specific gene groups.Key words: Oryza sativa Homeobox 6 (OSH6) genes, Ds insertion lines, OSH15 mutant

Glycosylation characterization of therapeutic mAbs by top- and middle-down mass spectrometry

A reference monoclonal antibody IgG1 and a fusion IgG protein were analyzed by top- and middle-down mass spectrometry with multiple fragmentation techniques including electron transfer dissociation (ETD) and matrix-assisted laser desorption ionization in-source decay (MALDI-ISD) to investigate heterogeneity of glycosylated protein species. Specifically, glycan structure, sites, relative abundance levels, and termini structural conformation were investigated by use of Fourier transform ion cyclotron resonance (FT-ICR) or high performance liquid chromatography electrospray ionization (HPLC-ESI) linked to an Orbitrap. Incorporating a limited enzymatic digestion by immunoglobulin G-degrading enzyme Streptococcus pyogenes (IdeS) with MALDI-ISD analysis extended sequence coverage of the internal region of the proteins without pre-fractionation. The data in this article is associated with the research article published in Journal of Proteomics (Tran et al., 2015)

Epigenetic memory in induced pluripotent stem cells.

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment