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81.
Duyilemi C. Ajonijebu Oualid Abboussi Vivienne A. Russell Musa V. Mabandla William M. U. Daniels 《Cellular and molecular life sciences : CMLS》2017,74(15):2735-2747
The detrimental effects of drug abuse are apparently not limited to individuals but may also impact the vulnerability of their progenies to develop addictive behaviours. Epigenetic signatures, early life experience and environmental factors, converge to influence gene expression patterns in addiction phenotypes and consequently may serve as mediators of behavioural trait transmission between generations. The majority of studies investigating the role of epigenetics in addiction do not consider the influence of social interactions. This shortcoming in current experimental approaches necessitates developing social models that reflect the addictive behaviour in a free-living social environment. Furthermore, this review also reports on the advancement of interventions for drug addiction and takes into account the emerging roles of histone deacetylase (HDAC) inhibitors in the etiology of drug addiction and that HDAC may be a potential therapeutic target at nucleosomal level to improve treatment outcomes. 相似文献
82.
Apolipoprotein M (apoM) is a novel apolipoprotein found mainly in high-density lipoproteins (HDL). Its function is yet to
be defined. ApoM (25 kDa) has a typical lipocalin ?-barrel fold and a hydrophobic pocket. Retinoids bind apoM but with low
affinity and may not be the natural ligands. ApoM retains its signal peptide, which serves as a hydrophobic anchor to the
lipoproteins. This prevents apoM from being lost in the urine. Approximately 5% of HDL carries an apoM molecule. ApoM in plasma
(1 μM) correlates strongly with both low-density lipoprotein (LDL) and HDL cholesterol, suggesting a link to cholesterol metabolism.
However, in casecontrol studies, apoM levels in patients with coronary heart disease (CHD) and controls were similar, suggesting
apoM levels not to affect the risk for CHD in humans. Experiments in transgenic mice suggested apoM to have antiatherogenic
properties; possible mechanisms include increased formation of pre-? HDL, enhanced cholesterol mobilization from foam cells,
and increased antioxidant properties.
Received 28 November 2008; received after revision 15 December 2008; accepted 16 December 2008 相似文献
83.
Large conductance, Ca2+-activated potassium (BK) channels are widely expressed throughout the animal kingdom and play important roles in many physiological
processes, such as muscle contraction, neural transmission and hearing. These physiological roles derive from the ability
of BK channels to be synergistically activated by membrane voltage, intracellular Ca2+ and other ligands. Similar to voltage-gated K+ channels, BK channels possess a pore-gate domain (S5–S6 transmembrane segments) and a voltage-sensor domain (S1–S4). In addition,
BK channels contain a large cytoplasmic C-terminal domain that serves as the primary ligand sensor. The voltage sensor and
the ligand sensor allosterically control K+ flux through the pore-gate domain in response to various stimuli, thereby linking cellular metabolism and membrane excitability.
This review summarizes the current understanding of these structural domains and their mutual interactions in voltage-, Ca2+ - and Mg2+ -dependent activation of the channel.
Received 25 September 2008; received after revision 23 October 2008; accepted 24 October 2008 相似文献
84.
Dynamic protein methylation in chromatin biology 总被引:1,自引:1,他引:0
85.
为了提高分布式多输入多输出(multiple input multiple output,MIMO)雷达的目标定位精度,分析了阵元、发射功率和信号带宽对定位精度的影响,进而提出一种将三者联合优化的资源分配算法。首先,以最小化目标的平方位置误差下限(squared position error bound,SPEB)为目标函数,建立了包含阵元、功率和带宽3个变量的优化模型;然后,通过推导最优功率分配矢量和带宽分配矢量的关系简化模型;最后利用凸松弛和循环最小化算法将优化问题转化成二阶锥形式,求解得到最优的资源分配策略。仿真结果表明,利用所提出的算法进行资源分配能明显提高目标的定位精度;信号有效带宽对目标定位精度的影响大于发射功率。 相似文献
86.
P. Huber S. Bouillot S. Elsen I. Attrée 《Cellular and molecular life sciences : CMLS》2014,71(10):1927-1941
Pseudomonas aeruginosa is a major human opportunistic pathogen and one of the most important causal agents of bacteremia. For non-blood-borne infection, bacterial dissemination requires the crossing of the vascular endothelium, the main barrier between blood and the surrounding tissues. Here, we investigated the effects of P. aeruginosa type 3 secretion effectors, namely ExoS, ExoT, and ExoY, on regulators of actin cytoskeleton dynamics in primary endothelial cells. ExoS and ExoT similarly affected the Lim kinase-cofilin pathway, thereby promoting actin filament severing. Cofilin activation was also observed in a mouse model of P. aeruginosa-induced acute pneumonia. Rho, Rac, and Cdc42 GTPases were sequentially inactivated, leading to inhibition of membrane ruffling, filopodia, and stress fiber collapse, and focal adhesion disruption. At the end of the process, ExoS and ExoT produced a dramatic retraction in all primary endothelial cell types tested and thus a rupture of the endothelial monolayer. ExoY alone had no effect in this context. Cell retraction could be counteracted by overexpression of actin cytoskeleton regulators. In addition, our data suggest that moesin is neither a direct exotoxin target nor an important player in this process. We conclude that any action leading to inhibition of actin filament breakdown will improve the barrier function of the endothelium during P. aeruginosa infection. 相似文献
87.
88.
Kärt Varendi Anmol Kumar Mari-Anne Härma Jaan-Olle Andressoo 《Cellular and molecular life sciences : CMLS》2014,71(22):4443-4456
Brain-derived neurotrophic factor (BDNF) is a secreted protein of the neurotrophin family that regulates brain development, synaptogenesis, memory and learning, as well as development of peripheral organs, such as angiogenesis in the heart and postnatal growth and repair of skeletal muscle. However, while precise regulation of BDNF levels is an important determinant in defining the biological outcome, the role of microRNAs (miRs) in modulating BDNF expression has not been extensively analyzed. Using in silico approaches, reporter systems, and analysis of endogenous BDNF, we show that miR-1, miR-10b, miR-155, and miR-191 directly repress BDNF through binding to their predicted sites in BDNF 3′UTR. We find that the overexpression of miR-1 and miR-10b suppresses endogenous BDNF protein levels and that silencing endogenous miR-10b increases BDNF mRNA and protein levels. Furthermore, we show that miR-1/206 binding sites within BDNF 3′UTR are used in differentiated myotubes but not in undifferentiated myoblasts. Finally, our data from two cell lines suggest that endogenous miR-1/206 and miR-10 family miRs act cooperatively in suppressing BDNF through their predicted sites in BDNF 3′UTR. In conclusion, our results highlight miR-1, miR-10b, miR-155, and miR-191 as novel regulators of BDNF long and short 3′UTR isoforms, supporting future research in different physiological and pathological contexts. 相似文献
89.
90.