Backbone assignment of human proliferating cell nuclear antigen

PCNA is an essential factor for DNA replication, repair, chromatin metabolism, and effector of cell-cycle regulatory signals. The assignment of backbone ¹H_N, ¹³C_α, ¹³CO, and ¹⁵N, and sidechain ¹³C_β resonances of the human PCNA homotrimeric ring (∼90 kDa, 261 residues) is reported here.     

How to evaluate the risk-benefit ratio of the low-dose hormone replacement therapy?

Since the results of the women health initiative study showing an overall negative risk-benefit ratio with 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate, the use of the lowest effective dose of steroids in hormone replacement therapy (HRT) is recommended.

A low-dose regimen appears to induce less side effects such as breast tenderness or leg pain than do higher dose preparations.

The decrease in hot flashes with low-dose estrogens, range 60–70%, is less than the 80–90% reduction with standard dosing. But this mean that 60–70% of menopausal women do not need higher doses.

The same applies to bone preservation which is dose dependent: the number of non-respondant women will be higher than with standard doses. However, randomized double-blind, placebo controls trials have defined positive effects on bone of low doses of HRT with adequate calcium and Vitamin D in elderly women. The use of bone densitometry and of biochemical markers of bone turnover is mandatory in women using low or ultra-low-dose preparations.

In spite of the lack of trials conducted with low-dose HRT, this treatment seems to be safer:

• the plasma levels of estradiol are lower; as far as breast cancer risk is concerned, the decrease of this subrogate marker is considered as favourable;

• the increase in breast density is less pronounced;

• the nurses's health study found a dose relationship for stroke, with no increase in risk with low-dose of estrogens;

• the effects on subrogate markers of cardiovascular risk seem to be more favourable.

Beside the low-dose HRT, one must consider some other facts:

• the “critical window” theory: it is biologically plausible that HRT, if started early after the menopause can slow the progression of coronary atherosclerosis;

• the way of administration of HRT: some observational studies have shown no increase in the risk of venous thromboembolism risk among women treated with transdermal estrogens;

• the progestogen used: a French cohort study recently performed found no increase in breast cancer risk with the use of micronized progesterone meanwhile the increase in risk observed with other progestogens was similar to the findings of the WHI study.

In the future, it is conceivable that more comprehensive pharmacogenomic studies will lead to effective algorithms for individualizing the right dose of steroids to be used in HRT.     

靶向α-酮戊二酸脱氢酶增强纳米银的抗菌作用

【目的】纳米银(silver nanoparticles,Ag NPs)的生物安全性一直受业界诟病,扩大纳米银的治疗窗将为治疗人和动物多耐药性细菌感染提供有效的备选药物。本研究拟用三羧酸循环的重要成员α-酮戊二酸(alpha-ketoglutaric acid,AKG)对纳米银进行表面修饰以提高其抗菌的生物安全性。【方法】芦丁在常温下合成纳米银,用全波长分光光度计、粒度仪及透射电镜进行表征。加1 mmol/L聚乙烯吡咯烷酮(polyvinylpyrrolidone,PVP)作为稳定剂(PVP-Ag NPs),另加10 mmol/L AKG作为封端剂(PVP-Ag NPs@AKG),比较2种纳米银的抗菌性及对人正常宫颈上皮细胞(human cervical epithelial cells,HCer Epic)的毒性作用,再分析2种纳米银对大肠杆菌(Escherichia coli) BW25113能量代谢、抗氧化应激和无氧呼吸相关基因表达等的影响。【结果】PVP-Ag NPs@AKG对多株革兰阳性细菌和革兰阴性细菌的最小抑菌浓度(minimal inhibit concentration,MIC)和最低杀菌浓度(minimum bactericidal concentration,MBC)均比PVP-Ag NPs低50%或50%以上,而对HCer Epic细胞的毒性无显著差异。与PVP-Ag NPs相比,PVP-Ag NPs@AKG在MIC浓度下对E.coli α-酮戊二酸脱氢酶活性的抑制作用增强,AKG蓄积,ATP水平显著降低,同时活性氧(reactive oxygen species,ROS)的水平显著升高,sox S表达上调,但是,厌氧呼吸相关的arc A、fnr、fdn H基因表达上调的程度显著降低。【结论】AKG修饰纳米银能通过靶向α-酮戊二酸脱氢酶抑制细菌的能量代谢,使其对氧化损伤更敏感,从而获得更强的抗菌能力,是一种扩大纳米银治疗窗的有效手段。     

自复寄生蜂的生殖特性及其对生物防治的影响

自复寄生蜂营雌雄异律发育,雌蜂为初级寄生蜂,雄蜂为复寄生蜂。依据寄主类型产下的相应性别的后代,其性比受到寄主数量、初级寄主与二级寄主的相对丰度等因素影响。自复寄生蜂能够寄生和取食初级寄主,抑制有害昆虫的种群数量,同时能够寄生和取食同种和异种寄生蜂幼虫,产生致死干扰竞争作用。复寄生二级寄主时,易感时间窗口主要集中在老熟幼虫至预蛹阶段。与同种二级寄主相比,自复寄生蜂更倾向于寄生异种二级寄主或无选择倾向性,取食时,更倾向于异种二级寄主。自复寄生蜂特殊的生殖方式使其对生物防治的影响备受争议。在评价其生物防治价值时,应对其正面影响和负面影响做出全面权衡。本文对自复寄生蜂的生殖特性、对同种和其他种类寄生蜂产生的致死干扰竞争作用及其对生物防治的影响等问题的国内外研究进展进行了综述,以期为利用这种天敌资源开展有害生物综合治理提供依据。