Polymorphisms in DNA Repair Genes (APEX1, XPD,XRCC1 and XRCC3) and Risk of Preeclampsia in a Mexican Mestizo Population

Variations in genes involved in DNA repair systems have been proposed as risk factors for the development of preeclampsia (PE). We conducted a case-control study to investigate the association of Human apurinic/apyrimidinic (AP) endonuclease (APEX1) Asp148Glu (rs1130409), Xeroderma Pigmentosum group D (XPD) Lys751Gln (rs13181), X-ray repair cross-complementing group 1 (XRCC) Arg399Gln (rs25487) and X-ray repair cross-complementing group 3 (XRCC3) Thr241Met (rs861539) polymorphisms with PE in a Mexican population. Samples of 202 cases and 350 controls were genotyped using RTPCR. Association analyses based on a χ² test and binary logistic regression were performed to determine the odds ratio (OR) and a 95% confidence interval (95% CI) for each polymorphism. The allelic frequencies of APEX1 Asp148Glu polymorphism showed statistical significant differences between preeclamptic and normal women (p = 0.036). Although neither of the polymorphisms proved to be a risk factor for the disease, the APEX1 Asp148Glu polymorphism showed a tendency of association (OR: 1.74, 95% CI = 0.96–3.14) and a significant trend (p for trend = 0.048). A subgroup analyses revealed differences in the allelic frequencies of APEX1 Asp148Glu polymorphism between women with mild preeclampsia and severe preeclampsia (p = 0.035). In conclusion, our results reveal no association between XPD Lys751Gln, XRCC Arg399Gln and XRCC3 Thr241Met polymorphisms and the risk of PE in a Mexican mestizo population; however, the results in the APEX1 Asp148Glu polymorphism suggest the need for future studies using a larger sample size.     

Synthesis, 3D‐QSAR,and Structural Modeling of Benzolactam Derivatives with Binding Affinity for the D2 and D3 Receptors

A series of 37 benzolactam derivatives were synthesized, and their respective affinities for the dopamine D₂ and D₃ receptors evaluated. The relationships between structures and binding affinities were investigated using both ligand‐based (3D‐QSAR) and receptor‐based methods. The results revealed the importance of diverse structural features in explaining the differences in the observed affinities, such as the location of the benzolactam carbonyl oxygen, or the overall length of the compounds. The optimal values for such ligand properties are slightly different for the D₂ and D₃ receptors, even though the binding sites present a very high degree of homology. We explain these differences by the presence of a hydrogen bond network in the D₂ receptor which is absent in the D₃ receptor and limits the dimensions of the binding pocket, causing residues in helix 7 to become less accessible. The implications of these results for the design of more potent and selective benzolactam derivatives are presented and discussed.     

From Cancer Therapy to Winemaking: The Molecular Structure and Applications of β-Glucans and β-1, 3-Glucanases

β-glucans are a diverse group of polysaccharides composed of β-1,3 or β-(1,3-1,4) linked glucose monomers. They are mainly synthesized by fungi, plants, seaweed and bacteria, where they carry out structural, protective and energy storage roles. Because of their unique physicochemical properties, they have important applications in several industrial, biomedical and biotechnological processes. β-glucans are also major bioactive molecules with marked immunomodulatory and metabolic properties. As such, they have been the focus of many studies attesting to their ability to, among other roles, fight cancer, reduce the risk of cardiovascular diseases and control diabetes. The physicochemical and functional profiles of β-glucans are deeply influenced by their molecular structure. This structure governs β-glucan interaction with multiple β-glucan binding proteins, triggering myriad biological responses. It is then imperative to understand the structural properties of β-glucans to fully reveal their biological roles and potential applications. The deconstruction of β-glucans is a result of β-glucanase activity. In addition to being invaluable tools for the study of β-glucans, these enzymes have applications in numerous biotechnological and industrial processes, both alone and in conjunction with their natural substrates. Here, we review potential applications for β-glucans and β-glucanases, and explore how their functionalities are dictated by their structure.     

熔渗温度和熔渗相组成对三维互穿网络结构(Mo,Ti)Six-RSiC复合材料组成、微观结构、力学和热学性能的影响

以RSiC为基体,通过MoSi2-Si-Ti合金活化熔渗(AMMI)工艺来制备三维互穿网络结构的(Mo,Ti)Six-RSiC复合材料。采用XRD、SEM、力学性能、热膨胀测试等方法研究了熔渗温度和熔渗相组成对复合材料组成、微观结构,力学和热膨胀系数等性能的影响。结果表明:采用AAMI法可获得具有三维互穿网络结构的(Mo,Ti)XSi2-RSiC复合材料,材料的组成主要为SiC、Si、TiSi2和(Mo0.2Ti0.8)Si2;随预熔配方中MoSi2含量和熔渗温度的增加,复合材料的室温力学性能均先增大后减小,采用MoSiTi-2配方1700℃熔渗所得复合材料的力学性能最佳,其弯曲强度、弹性模量和断裂韧性分别为136.8MPa、217.3GPa和2.45MPa·m^1/2,相比基体分别提高约44%,158%和75%;MoSiTi-2-S2.6-1700在1200℃的热膨胀系数约为4.51×10^-6℃^-1,且基体密度对复合材料CTE的影响高于熔渗相组成;随温度升高,复合材料的弯曲强度增加,1400℃时,其弯曲强度为189.4MPa,比室温提高了约38%;随氧化时间增加,MoSiTi-2-S2.6-1700的室温力学性能先增加后降低,氧化60h时,材料的弯曲强度和弹性模量达到最大,分别为146.8MPa和212.08GPa,与未氧化试样相比提高了约16.2%和51.7%,即使氧化100h,材料的力学性能仍高于初始值。