Association between APOC1 Polymorphism and Alzheimer’s Disease: A Case-Control Study and Meta-Analysis

Background

Previous association studies examining the relationship between the APOC1 polymorphism and susceptibility to Alzheimer’s disease (AD) have shown conflicting results, and it is not clear if an APOC1 variant acts as a genetic risk factor in AD etiology across multiple populations.

Methods

To confirm the risk association between APOC1 and AD, we designed a case-control study and also performed a meta-analysis of previously published studies.

Results

Seventy-nine patients with AD and one hundred fifty-six unrelated controls were included in case-control study. No association was found between the variation of APOC1 and AD in stage 1 of our study. However, our meta-analysis pooled a total of 2092 AD patients and 2685 controls. The APOC1 rs11568822 polymorphism was associated with increased AD risk in Caucasians, Asians and Caribbean Hispanics, but not in African Americans. APOE ε4 carriers harboring the APOC1 insertion allele, were more prevalent in AD patients than controls (χ² = 119.46, OR = 2.79, 95% CI = 2.31–3.36, P<0.01).

Conclusions

The APOC1 insertion allele, in combination with APOE ε4, likely serves as a potential risk factor for developing AD.     

Cytopathology of Tomato torrado virus Infection in Tomato and Nicotiana benthamiana

Electron microscopy studies were carried out to investigate the cytopathological changes induced in tomato leaves by Tomato torrado virus (ToTV) that infects tomato plants worldwide causing severe necrotic symptoms. Plants infected with one of the Polish isolates of ToTV were used for cytopathological research. The results revealed severe cellular alterations, especially in Solanum lycopersicum. Moreover, it was shown that crystalline aggregates of virions occurred not only within the phloem cells as it has been previously reported.     

House dust mite extract activates apical Cl− channels through protease‐activated receptor 2 in human airway epithelia

Adequate fluid secretion from airway mucosa is essential for maintaining mucociliary clearance, and fluid hypersecretion is a prominent feature of inflammatory airway diseases such as allergic rhinitis. House dust mite extract (HDM) has been reported to activate protease‐activated receptors (PARs), which play various roles in airway epithelia. However, the role of HDM in regulating ion transporters and fluid secretion has not been investigated. We examined the effect of HDM on ion transport in human primary nasal epithelial cells. The Ca²⁺‐sensitive dye Fura2‐AM was used to determine intracellular Ca²⁺ concentration ([Ca²⁺]_i) by means of spectrofluorometry in human normal nasal epithelial cells (NHNE). Short‐circuit current (Isc) was measured using Ussing chambers. Fluid secretion from porcine airway mucosa was observed by optical measurement. HDM extract (10 µg/Ml) effectively cleaved the PAR‐2 peptide and induced an increase of [Ca²⁺]_i that was abolished by desensitization with trypsin, but not with thrombin. Apical application of HDM‐induced Isc sensitive to both a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor and a Ca²⁺‐activated Cl^? channel (CaCC) inhibitor. HDM extract also stimulated fluid secretion from porcine airway mucosa. HDM extract activated PAR‐2 and apical Cl^? secretion via CaCC and CFTR, and HDM‐induced fluid secretion in porcine airway mucosa. Our results suggest a role for PAR‐2 in mucociliary clearance and fluid hypersecretion of airway mucosa in response to air‐borne allergens such as HDM. J. Cell. Biochem. 109: 1254–1263, 2010. © 2010 Wiley‐Liss, Inc.     

Structural insight into the bacterial mucinase StcE essential to adhesion and immune evasion during enterohemorrhagic E. coli infection

Mucin glycoproteins with large numbers of O-linked glycosylations comprise the mucosal barrier lining the mammalian gastrointestinal tract from mouth to gut. A critical biological function of mucins is to protect the underlying epithelium from infection. Enterohemorrhagic Escherichia coli (EHEC), the mediator of severe food- and water-borne disease, can breach this barrier and adhere to intestinal cells. StcE, a ～100 kDa metalloprotease secreted by EHEC, plays a pivotal role in remodeling the mucosal lining during infection. To obtain mechanistic insight into its function, we have determined the structure of StcE. Our data reveal a dynamic, multidomain architecture featuring an unusually large substrate-binding cleft and a prominent polarized surface charge distribution highly suggestive of an electrostatic role in substrate targeting. The observation of key conserved motifs in the active site allows us to propose the structural basis for the specific recognition of α-O-glycan-containing substrates. Complementary biochemical analysis provides further insight into its distinct substrate specificity and binding stoichiometry.     

妊娠相关脑卒中39 例临床分析

目的:探讨妊娠相关脑卒中的发病原因、临床表现、母婴结局、治疗及预防措施。方法:回顾性分析2001年1月-2013年12月我院共收治的妊娠相关脑卒中39例患者的临床资料。结果:39例患者中,发生在妊娠期21例,产褥期18例。经电子计算机断层扫描(CT)、磁共振成像(MRI)、磁共振动脉血管造影(MRA)、磁共振脑静脉血管成像(MRV)、数字减影血管造影术(DSA)和腰椎穿刺等检查明确诊断,诊断出血性脑卒中7例,脑梗死3例,脑静脉窦血栓(CVST)29例,均给予相应的抢救及治疗。16例早期、中期妊娠患者行人工流产术或利凡诺羊膜腔内注射穿刺引产终止妊娠,5例患者行剖宫产终止妊娠。患者治愈出院15例,6例死亡,14例遗留不同程度的肢体活动障碍或语言障碍,家属放弃治疗出院4例。结论:妊娠相关脑卒中危险因素主要包括子痫前期、心源性栓塞、脑血管畸形、脑动脉瘤、水电解质紊乱等代谢障碍性疾病及产褥感染等。其发病急、病死率高,故需提高对本病的认识,定期产前检查,及时发现高危因素,早诊断及时治疗,选择适当的时机及方式终止妊娠是改善妊娠相关脑卒中患者预后的关键。     

Features of expression of the <Emphasis Type="Italic">PsSst1</Emphasis> and <Emphasis Type="Italic">PsIgn1</Emphasis> genes in nodules of pea (<Emphasis Type="Italic">Pisum sativum</Emphasis> L.) symbiotic mutants

The sequences of the PsSst1 and PsIgn1 genes of pea (Pisum sativum L.) homologous to the symbiotic LjSST1 and LjIGN1 genes of Lotus japonicus (Regel.) K. Larsen are determined. The expression level of PsSst1 and PsIgn1 genes is determined by real-time PCR in nodules of several symbiotic mutants and original lines of pea. Lines with increased (Sprint-2Fix^– (Pssym31)) and decreased (P61 (Pssym25)) expression level of both genes are revealed along with the lines characterized by changes in the expression level of only one of these genes. The revealed features of the PsSst1 and PsIgn1 expression allow us to expand the phenotypic characterization of pea symbiotic mutants. In addition, PsSst1 and PsIgn1 cDNA is sequenced in selected mutant lines, characterized by a decreased expression level of these genes in nodules, but no mutations are found.     

Effects of ammonium treatment on the protein and chlorophyll contents and the number of ribosomes in Chlamydomonas reinhardtii cells

The effects of exogenous ammonium on total protein and chlorophyll contents and the number of ribosomes in Chlamydomonas reinhardtii (Sager) green alga cells were studied. The absence of ammonium from nutrient medium resulted in a twofold drop in the number of ribosomes in the cytoplasm. The chlorophyll content of the cells grown on ammonium-free nitrate-containing medium insignificantly increased. The increase in the ribosome number in the presence of exogenous ammonium was not accompanied by the elevation of total cellular protein and did not depend on the levels of mRNA of rps6, a small ribosome subunit protein, and the 18S rRNA. Possible reasons for the effect of exogenous ammonium during ribosome biogenesis are discussed.     

A registry for exposure and population health in the Altai region affected by fallout from the Semipalatinsk nuclear test site

A registry of the rural population in the Altai region exposed to fallout from nuclear tests at the Semipalatinsk test site (STS) was established more than four decades after the first Soviet nuclear explosion on August 29, 1949. Information about individuals living in an exposed and a control area was collected using all available local sources, such as kolkhoz documentation, school registries, medical treatment records and interviews with residents. As a result, a database comprising an exposed group of 39 179 individuals from 53 Altai region villages, 6769 external and 3303 internal controls was compiled. For several settlements, effective dose estimates reached the level of 1.5 Sv, while the average effective dose estimate in the exposed group was 340 mSv. Dosimetric data, vital status information and health records gathered at rayon and village medical facilities are held in the registry. Cause-of-death information for deceased residents is obtained from death registration forms archived at the Altai region vital statistics office. At present, a follow-up of approximately 40% of the population exposed in 1949 has been done. More will be added by searching for migrants to the larger towns of the Altai region, i.e. Barnaul, Rubtsovsk and Biisk. In order to assess the influence of radiation exposure, analytical studies with a case-control design for stomach and lung cancer are currently being prepared. The number of known cases is sufficient to detect an odds ratio of 1.5 at the 95% confidence level. Epidemiological studies in populations affected by fallout from STS may be equally important to the atomic bomb survivors’ study for the direct quantification of radiation effects. The range of exposure rates experienced will extend the acute high-dose-rate findings from Hiroshima/Nagasaki towards acute and protracted lower exposures, which are more relevant for radiation protection issues. Received: 3 March 1999 / Accepted in revised form: 8 June 1999