Enhanced expression of microrna-1273g-3p contributes to alzheimer’s disease pathogenesis by regulating the expression of mitochondrial genes

Alzheimer’s disease (AD) is the most common form of dementia in the elderly population, but its underlying cause has not been fully elucidated. Recent studies have shown that microRNAs (miRNAs) play important roles in regulating the expression levels of genes associated with AD development. In this study, we analyzed miRNAs in plasma and cerebrospinal fluid (CSF) from AD patients and cognitively normal (including amyloid positive) individuals. miR-1273g-3p was identified as an AD-associated miRNA and found to be elevated in the CSF of early-stage AD patients. The overexpression of miR-1273g-3p enhanced amyloid beta (Aβ) production by inducing oxidative stress and mitochondrial impairments in AD model cell lines. A biotin-streptavidin pull-down assay demonstrated that miR-1273g-3p primarily interacts with mitochondrial genes, and that their expression is downregulated by miR-1273g-3p. In particular, the miR-1273g-3p-target gene TIMM13 showed reduced expression in brain tissues from human AD patients. These results suggest that miR1273g-3p expression in an early stage of AD notably contributes to Aβ production and mitochondrial impairments. Thus, miR-1273g-3p might be a biomarker for early diagnosis of AD and a potential therapeutic target to prevent AD progression

Immunogenicity and Safety of Diphtheria-tetanus Vaccine in Adults

This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level (<0.1 U/mL). After the first dose of Td vaccine, 92.6% and 77.6% of subjects gained protective antibody concentrations (≥0.1 U/mL) for diphtheria and tetanus, with an increase to 99.6% and 100% after the third dose. Local and systemic adverse events occurred in 37.9% and 15.5% of the subjects. No serious adverse event requiring an unscheduled hospital visit occurred. In conclusion, three-doses of Td vaccination to unimmunized adults are safe and effective in inducing protective immunity against diphtheria and tetanus

Cystatin C as an Early Biomarker of Nephropathy in Patients with Type 2 Diabetes

This study was done to evaluate clinical usefulness of cystatin C levels of serum and urine in predicting renal impairment in normoalbuminuric patients with type 2 diabetes and to evaluate the association between albuminuria and serum/urine cystatin C. Type 2 diabetic patients (n = 332) with normoalbuminuria (n = 210), microalbuminuria (n = 83) and macroalbuminuria (n = 42) were enrolled. Creatinine, urinary albumin levels, serum/urine cystatin C and estimated glomerular filtration rate (eGFR by MDRD [Modification of Diet in Renal Disease] and CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equations) were determined. The cystatin C levels of serum and urine increased with increasing degree of albuminuria, reaching higher levels in macroalbuminuric patients (P < 0.001). In multiple regression analysis, serum cystatin C was affected by C-reactive protein (CRP), sex, albumin-creatinine ratio (ACR) and eGFR. Urine cystatin C was affected by triglyceride, age, eGFR and ACR. In multivariate logistic analysis, cystatin C levels of serum and urine were identified as independent factors associated with eGFR < 60 mL/min/1.73 m2 estimated by MDRD equation in patients with normoalbuminuria. On the other hand, eGFR < 60 mL/min/1.73 m2 estimated by CKD-EPI equation was independently associated with low level of high-density lipoprotein in normoalbuminuric patients. The cystatin C levels of serum and urine could be useful markers for renal dysfunction in type 2 diabetic patients with normoalbuminuria

IS6110-Restriction Fragment Length Polymorphism and Spoligotyping Analysis of Mycobacterium tuberculosis Clinical Isolates for Investigating Epidemiologic Distribution in Korea

The Beijing family of Mycobacterium tuberculosis has been emerging in the world. However, there are few nationwide data of genotypic distribution in Korea. This study aimed to identify the genotypic diversity of clinical isolates of M. tuberculosis and to demonstrate the population of Beijing family in Korea. We collected 96 clinical M. tuberculosis isolates from 11 university hospitals nationwide in Korea from 2008 to 2009. We observed 24 clusters in IS6110-RFLP analysis and 19 patterns in spoligotyping. Seventy-five isolates were confirmed to be Beijing family. Two isolates of the K strain and 12 isolates of the K family strain were also found. We found that drug resistance phenotypes were more strongly associated with Beijing family than non-Beijing family (P=0.003). This study gives an overview of the distribution of genotypes of M. tuberculosis in Korea. These findings indicate that we have to pay more attention to control of M. tuberculosis strains associated with the Beijing family

P130Cas Attenuates Epidermal Growth Factor (EGF) Receptor Internalization by Modulating EGF-Triggered Dynamin Phosphorylation

BACKGROUND: Endocytosis controls localization-specific signal transduction via epidermal growth factor receptor (EGFR), as well as downregulation of that receptor. Extracellular matrix (ECM)-integrin coupling induces formation of macromolecular complexes that include EGFR, integrin, Src kinase and p130Cas, resulting in EGFR activation. In addition, cell adhesion to ECM increases EGFR localization at the cell surface and reduces EGFR internalization. The molecular mechanisms involved are not yet well understood. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the molecular mechanism by which p130Cas affects the endocytic regulation of EGFR. Biochemical quantification revealed that cell adhesion to fibronectin (FN) increases total EGFR levels and its phosphorylation, and that p130Cas is required for this process. Measurements of Texas Red-labeled EGF uptake and cell surface EGFR revealed that p130Cas overexpression reduces EGF-induced EGFR internalization, while p130Cas depletion enhances it. In addition, both FN-mediated cell adhesion and p130Cas overexpression reduce EGF-stimulated dynamin phosphorylation, which is necessary for EGF-induced EGFR internalization. Coimmunoprecipitation and GST pull-down assays confirmed the interaction between p130Cas and dynamin. Moreover, a SH3-domain-deleted form of p130Cas, which shows diminished binding to dynamin, inhibits dynamin phosphorylation and EGF uptake less effectively than wild-type p130Cas. CONCLUSIONS/SIGNIFICANCE: Our results show that p130Cas plays an inhibitory role in EGFR internalization via its interaction with dynamin. Given that the EGFR internalization process determines signaling density and specificity in the EGFR pathway, these findings suggest that the interaction between p130Cas and dynamin may regulate EGFR trafficking and signaling in the same manner as other endocytic regulatory proteins related to EGFR endocytosis

Prevalence of Anti-Ganglioside Antibodies and Their Clinical Correlates with Guillain-Barre Syndrome in Korea: A Nationwide Multicenter Study

Background and Purpose No previous studies have investigated the relationship between various anti-ganglioside antibodies and the clinical characteristics of Guillain-Barre syndrome (GBS) in Korea. The aim of this study was to determine the prevalence and types of anti-ganglioside antibodies in Korean GBS patients, and to identify their clinical significance. Methods Serum was collected from patients during the acute phase of GBS at 20 university-based hospitals in Korea. The clinical and laboratory findings were reviewed and compared with the detected types of anti-ganglioside antibody. Results Among 119 patients, 60 were positive for immunoglobulin G (IgG) or immunoglobulin M antibodies against any type of ganglioside (50%). The most frequent type was IgG anti-GM1 antibody (47%), followed by IgG anti-GT1a (38%), IgG anti-GD1a (25%), and IgG anti-GQ1b (8%) antibodies. Anti-GM1-antibody positivity was strongly correlated with the presence of preceding gastrointestinal infection, absence of sensory symptoms or signs, and absence of cranial nerve involvement. Patients with anti-GD1a antibody were younger, predominantly male, and had more facial nerve involvement than the antibody-negative group. Anti-GT1a-antibody positivity was more frequently associated with bulbar weakness and was highly associated with ophthalmoplegia when coupled with the coexisting anti-GQ1b antibody. Despite the presence of clinical features of acute motor axonal neuropathy (AMAN), 68% of anti-GM1- or anti-GD1a-antibody-positive cases of GBS were diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (AMP) by a single electrophysiological study. Conclusions Anti-ganglioside antibodies were frequently found in the serum of Korean GBS patients, and each antibody was correlated strongly with the various clinical manifestations. Nevertheless, without an anti-ganglioside antibody assay, in Korea AMAN is frequently misdiagnosed as AIDP by single electrophysiological studies.OAIID:oai:osos.snu.ac.kr:snu2014-01/102/0000004487/14SEQ:14PERF_CD:SNU2014-01EVAL_ITEM_CD:102USER_ID:0000004487ADJUST_YN:YEMP_ID:A075641DEPT_CD:801CITE_RATE:1.807FILENAME:kimjk-anti ganlioside ab-gbs-j clin neurol-2014-10(2)94.pdfDEPT_NM:의학과SCOPUS_YN:YCONFIRM:

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong