Association analysis of monoamine oxidase A gene and bipolar affective disorder in Han Chinese

<p>Abstract</p> <p>Background</p> <p>Monoamine oxidase A (MAOA) is a mitochondrial enzyme involved in degrading several different biological amines, including serotonin. Although several pieces of evidence suggested that MAOA is important in the etiology of bipolar affective disorder (BPD), associations for markers of the MAOA gene with BPD were not conclusive and the association has not been investigated in Taiwanese population. This study was designed to illustrate the role of MAOA in the etiology of BPD in Han Chinese.</p> <p>Methods</p> <p>Two markers, a dinucleotide polymorphism in exon 2 and a functional uVNTR on the promoter of the <it>MAOA </it>gene, were used to study the genetic association in 108 unrelated patients with BPD and 103 healthy controls. Allelic distributions of two polymorphisms were analyzed and, caused the MAOA located at X chromosome, haplotype association was performed using haplotype unambiguously assigned in male participants.</p> <p>Results</p> <p>While no difference in allelic distributions of two MAOA polymorphisms was found, the risk haplotype 114S was associated with BPD in male patients (<it>P </it>= 0.03). The significance, however, was not found in female patients with 114S haplotype.</p> <p>Conclusion</p> <p>Results from this study suggest that MAOA may have a gender-specific and small effect on the etiology of BPD in Taiwan. Due to the limited sample size, results from this study need to be confirmed in replicates.</p

Clinicopathologic Evaluation of Prognostic Factors for Squamous Cell Carcinoma of the Buccal Mucosa

BackgroundThe purpose of this research was to evaluate the prognostic significance of clinicopathologic variables on the survival rate for squamous cell carcinoma of the buccal mucosa (BMSCC). We analyzed the outcomes of surgical therapy for this aggressive cancer and compared these results with those in the literature.MethodsWe reviewed the medical charts of 172 patients treated in our institution between 1990 and 2005. There were 22 patients excluded from our studies: 20 patients with advanced tumors who received no treatment or palliative treatment, and 2 patients who had received preoperative radiotherapy (RT). The remaining 150 patients were treated with surgeries and among them, 56 patients had undergone postoperative RT. The influence of clinicopathologic factors on the survival rate was analyzed with the Kaplan-Meier method and log-rank test. Multivariate analysis was assessed with Cox's regression model.ResultsThere were 148 males and 2 females, with a mean age of 53.5 years. The prevalence rate of habitual betel quid chewing documented in charts among 113 patients was 75%. The 5-year overall survival rate and disease-specific survival rate for all patients were 64% and 69%, respectively. For patients with stages I, II, III, and IV disease, the 5-year disease-specific survival rates were 90%, 77%, 52%, and 47%, respectively (p< 0.001). According to the multivariate analysis, the pathologic staging and histologic grading of the tumor were independently the important prognostic factors affecting survival rate. There were 80 patients who developed locoregional recurrence in lymph nodes in the follow-up diagnoses. Distant metastases occurred in 14 patients, with 11 of them also having locoregional recurrence. The distant metastases were found in the lungs (8/14), T-spine (3/14), liver (2/14) and brain (1/14).ConclusionPathologic stage and histologic grade are the most important prognostic factors

Integrin-mediated membrane blebbing is dependent on the NHE1 and NCX1 activities.

Integrin-mediated signal transduction and membrane blebbing have been well studied to modulate cell adhesion, spreading and migration^1-6^. However, the relationship between membrane blebbing and integrin signaling has not been explored. Here we show that integrin-ligand interaction induces membrane blebbing and membrane permeability change. We found that sodium-proton exchanger 1 (NHE1) and sodium-calcium exchanger 1 (NCX1) are located in the membrane blebbing sites and inhibition of NHE1 disrupts membrane blebbing and decreases membrane permeability change. However, inhibition of NCX1 enhances cell blebbing to cause cell swelling which is correlated with an intracellular sodium accumulation induced by NHE17. These data suggest that sodium influx induced by NHE1 is a driving force for membrane blebbing growth, while sodium efflux induced by NCX1 in a reverse mode causes membrane blebbing retraction. Together, these data reveal a novel function of NHE1 and NCX1 in membrane permeability change and blebbing and provide the link for integrin signaling and membrane blebbing

CFTR Mutation Analysis of a Caucasian Father with Congenital Bilateral Absence of Vas Deferens, a Taiwanese Mother, and Twins Resulting from ICSI Procedure

Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is one of the most common autosomal recessive diseases in Caucasians. We screened for the CFTR gene mutation in a Caucasian father with congenital bilateral absence of the vas deferens (CBAVD), a Taiwanese mother, and twins resulting from an intracytoplasmic single sperm injection (ICSI) procedure. DNA fragments that showed abnormal banding patterns on temporal temperature gradient gel electrophoresis analysis followed by analysis of DNA sequence was used. The Caucasian father with CBAVD had ΔF508 and p.L375F mutations. The two children were heterozygous for the ΔF508 and p.L375F mutations, respectively. Mutation analysis of the CFTR gene should always be recommended for infertile couples seeking ICSI. The possibility of the children resulting from ICSI being a victim or carrier of CBAVD or CF, especially when the father is Caucasian with CBAVD, should be discussed during genetic counseling

Impaired post-stroke collateral circulation in sickle cell anemia mice

Patients with sickle cell anemia (SCA) have a high incidence of ischemic stroke, but are usually excluded from thrombolytic therapy due to concerns for cerebral hemorrhage. Maladaptation to cerebral ischemia may also contribute to the stroke propensity in SCA. Here we compared post-stroke cortical collateral circulation in transgenic sickle (SS) mice, bone marrow grafting-derived SS-chimera, and wildtype (AA) controls, because collateral circulation is a critical factor for cell survival within the ischemic penumbra. Further, it has been shown that SS mice develop poorer neo-collateral perfusion after limb ischemia. We used the middle cerebral artery (MCA)-targeted photothrombosis model in this study, since it is better tolerated by SS mice and creates a clear infarct core versus peri-infarct area. Compared to AA mice, SS mice showed enlarged infarction and lesser endothelial proliferation after photothrombosis. SS-chimera showed anemia, hypoxia-induced erythrocyte sickling, and attenuated recovery of blood flow in the ipsilateral cortex after photothrombosis. In AA chimera, cerebral blood flow in the border area between MCA and the anterior cerebral artery (ACA) and posterior cerebral artery (PCA) trees improved from 44% of contralateral level after stroke to 78% at 7 d recovery. In contrast, blood flow in the MCA-ACA and MCA-PCA border areas only increased from 35 to 43% at 7 d post-stroke in SS chimera. These findings suggest deficits of post-stroke collateral circulation in SCA. Better understanding of the underpinnings may suggest novel stroke therapies for SCA patients

Nanowrinkled Carbon Aerogels Embedded with FeN x Sites as Effective Oxygen Electrodes for Rechargeable Zinc-Air Battery.

Rational design of single-metal atom sites in carbon substrates by a flexible strategy is highly desired for the preparation of high-performance catalysts for metal-air batteries. In this study, biomass hydrogel reactors are utilized as structural templates to prepare carbon aerogels embedded with single iron atoms by controlled pyrolysis. The tortuous and interlaced hydrogel chains lead to the formation of abundant nanowrinkles in the porous carbon aerogels, and single iron atoms are dispersed and stabilized within the defective carbon skeletons. X-ray absorption spectroscopy measurements indicate that the iron centers are mostly involved in the coordination structure of FeN4, with a minor fraction (ca. 1/5) in the form of FeN3C. First-principles calculations show that the FeN x sites in the Stone-Wales configurations induced by the nanowrinkles of the hierarchically porous carbon aerogels show a much lower free energy than the normal counterparts. The resulting iron and nitrogen-codoped carbon aerogels exhibit excellent and reversible oxygen electrocatalytic activity, and can be used as bifunctional cathode catalysts in rechargeable Zn-air batteries, with a performance even better than that based on commercial Pt/C and RuO2 catalysts. Results from this study highlight the significance of structural distortions of the metal sites in carbon matrices in the design and engineering of highly active single-atom catalysts

The microtubule-associated protein, EB1, links AIM2 inflammasomes with autophagy-dependent secretion

Inflammasomes are multi-protein complexes that regulate chronic inflammation-associated diseases by inducing interleukin-1 β (IL-1β) secretion. Numerous components involved in inflammasome activation have been identified, but the mechanisms of inflammasome-mediated IL-1β secretion have not yet been fully explored. Here, we demonstrate that end-binding protein 1 (EB1), which is required for activation of AIM2 inflammasome complex, links the AIM2 inflammasome to autophagy-dependent secretion. Imaging studies revealed that AIM2 inflammasomes colocalize with microtubule organizing centers and autophagosomes. Biochemical analyses showed that poly(dA-dT)-activated AIM2 inflammasomes induce autophagy and IL-1β secretion in an LC3-dependent fashion. Furthermore, depletion of EB1 decreases autophagic shedding and intracellular trafficking. Finally, we found that the 5′-AMP activated protein kinase may regulate this EB1-mediated autophagy-based inflammasome-induced secretion of IL-1β. These findings reveal a novel EB1-mediated pathway for the secretion of IL-1β