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The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress.

A real representation of complex polynomial matrices in the framework of conjugate product is first proposed, and some interesting properties of the proposed real representation are given. With the real representations as tools, alternative proofs for some properties of conjugate product are given. In addition, the concept of real determinant is proposed for complex polynomial matrices in the framework of conjugate product, and based on the real determinant the invertibility in the framework of conjugate product is investigated. These results imply that the proposed real representation has potential applications in the further investigation of conjugate product. [ABSTRACT FROM AUTHOR]

Shi, Hong, Hui-Zhen Wang, and Zhiguo Wang. Extracellular [Ba.sup.2+] blocks the cardiac transient outward [K.sup.+] current. Am. J. Physiol. Heart Circ. Physiol. 278: H295-H299, 2000.--[Ba.sup.2+] is widely used as a tool in patch-clamp studies because of its ability to block a variety of [K.sup.+] channels and to pass [Ca.sup.2+] channels. Its potential ability to block the cardiac transient outward [K.sup.+] current ([I.sub.to]) has not been clearly documented. We performed whole cell patch-clamp studies in canine ventricular and atrial myocytes. Extracellular application of [Ba.sup.2+] produced potent inhibition of [I.sub.to] with an [IC.sub.50] of ~40 [micro]M. The effects were voltage independent, and the inactivation kinetics were not altered by [Ba.sup.2+]. The potency of [Ba.sup.2+] was ~10 times higher than that of 4-aminopyridine (a selective [I.sub.to] blocker with an [IC.sub.50] of 430 [micro]M) under identical conditions. By comparison, [Ba.sup.2+] blockade of the inward rectifier [K.sup.+] current was voltage dependent; the [IC.sub.50] was ~20 times lower (2.5 [micro]M) than that for [I.sub.to] when determined at - 100 mV and was comparable to [i.sub.to] as determined at -60 mV ([IC.sub.50] = 26 [micro]M). [Ba.sup.2+] concentrations of [is less than or equal to] 1 mM or higher failed to block ultrarapid delayed rectifier [K.sup.+] current. Our data suggest that [Ba.sup.2+] can be considered a potent blocker of [I.sub.to]. patch clamp; cardiac myocytes; 4-aminopyridine; inward rectifier potassium current; ultrarapid delayed rectifier potassium current

Wang, Hui-Zhen, Hong Shi, Shu-Jie Liao, and Zhiguo Wang. Inactivation gating determines nicotine blockade of human HERG channels. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1081-H1088, 1999.--We have previously found that nicotine blocked multiple [K.sup.+] currents, including the rapid component of delayed rectifier [K.sup.+] currents ([I.sub.Kr]), by interacting directly with the channels. To shed some light on the mechanisms of interaction between nicotine and channels, we performed detailed analysis on the human ether-a-go-go-related gene (HERG) channels, which are believed to be equivalent to the native [I.sub.Kr] when expressed in Xenopus oocytes. Nicotine suppressed the HERG channels in a concentration-dependent manner with greater potency with voltage protocols, which favor channel inactivation. Nicotine caused dramatic shifts of the voltage-dependent inactivation curve to more negative potentials and accelerated the inactivation process. Conversely, maneuvers that weakened the channel inactivation gating considerably relieved the blockade. Elevating the extracellular [K.sup.+] concentration from 5 to 20 mM increased the nicotine concentration (by ~100-fold) needed to achieve the same degree of inhibition. Moreover, nicotine lost its ability to block the HERG channels when a single mutation was introduced to a residue located after transmembrane domain 6 (S631A) to remove the rapid channel inactivation. Our data suggest that the inactivation gating determines nicotine blockade of the HERG channels. Xenopus oocyte; voltage-clamp techniques

Maternally expressed gene 3 (MEG3), a long noncoding RNA (lncRNA) has been dysregulated in various tumors. However, the expression level and functional role of MEG3 in the progression of respiratory syncytial virus (RSV) infection remains to be elucidated. The present study quantified the expression level of MEG3 in the nasopharyngeal (NPA) samples of RSV‑infected patients and in BEAS‑2B cells infected with RSV. The findings of the present study demonstrated that the expression level of lncRNA MEG3 was reduced in the NPA samples of RSV‑infected patients and in BEAS‑2B cells infected with RSV. In vitro transfection revealed increased mRNA expression levels of toll‑like receptor 4 (TLR4), tumor necrosis factor‑α (TNFα) and interleukin (IL)‑8 following RSV infection in BEAS‑2B cells. Additionally, ectopic expression of MEG3 reduced the expression level of TLR4, subsequently suppressing the mRNA expression levels of TNFα and IL‑8, indicating the protective role of MEG3 in the process of RSV infection. It is of note, that RSV infection‑induced p38 mitogen activated protein kinase (MAPK) and nuclear factor‑κB (NF‑κB) activation was partly abolished by overexpression of MEG3. In conclusion, to the best of our knowledge, the present study provided the first evidence that lncRNA MEG3 expression level was reduced in the NPA samples of patients with RSV infection and RSV‑infected cells. Additionally, it was demonstrated that MEG3 protected human airway epithelial cells from RSV infection, primarily by suppressing TLR4‑dependent p38 MAPK and NF‑κB signaling. [ABSTRACT FROM AUTHOR]