Mechanical strain induced phospho-proteomic signaling in uterine smooth muscle cells

Mechanical strain associated with the expanding uterus correlates with increased preterm birth rates. Mechanical signals result in a cascading network of protein phosphorylation events. These signals direct cellular activities and may lead to changes in contractile phenotype and calcium signaling. In this study, the complete phospho-proteome of uterine smooth muscle cells subjected to mechanical strain for 5 min was compared to un-strained controls. Statistically significant, differential phosphorylation events were annotated by Ingenuity Pathway Analysis to elucidate mechanically induced phosphorylation networks. Mechanical strain leads to the direct activation of ERK1/2, HSPB1, and MYL9, in addition to phosphorylation of PAK2, vimentin, DOCK1, PPP1R12A, and PTPN11 at previously unannotated sites. These results suggest a novel network reaction to mechanical strain and reveal proteins that participate in the activation of contractile mechanisms leading to preterm labor.     

单胎头位初产妇产程图分析

目的：探讨存在难产因素初产妇产程图的临床意义。方法：对2009年6月至2010年6月在济南军区总医院住院分娩的326例单胎头位初产妇的产程图进行回顾性分析。结果：产程图异常组中难产因素的构成比和剖宫产率均高于产程图正常组;存在难产因素的组别（胎方位异常组、宫缩乏力组、巨大儿组）产程中各阶段时限均较正常产妇组长,宫颈扩张速度均较正常组慢,胎头位置均高于正常组,以上差异均有统计学意义（P〈0．05）。结论：在产程中对产程图中各阶段时限、宫颈扩张速度及胎头位置等指标进行监测,来预测和及时发现头位难产因素的存在,及时给予处理,改善母儿预后。     

单胎头位初产妇产程图分析

目的:探讨存在难产因素初产妇产程图的临床意义。方法:对2009年6月至2010年6月在济南军区总医院住院分娩的326例单胎头位初产妇的产程图进行回顾性分析。结果:产程图异常组中难产因素的构成比和剖宫产率均高于产程图正常组;存在难产因素的组别(胎方位异常组、宫缩乏力组、巨大儿组)产程中各阶段时限均较正常产妇组长,宫颈扩张速度均较正常组慢,胎头位置均高于正常组,以上差异均有统计学意义(P<0.05)。结论:在产程中对产程图中各阶段时限、宫颈扩张速度及胎头位置等指标进行监测,来预测和及时发现头位难产因素的存在,及时给予处理,改善母儿预后。     

罗哌卡因复合舒芬太尼在潜伏期分娩镇痛中的应用效果

目的:探讨罗哌卡因复合舒芬太尼在潜伏期分娩镇痛中的应用效果。方法:择取2015年1月~2016年1月我院收治的产妇102例,随机分为A、B、C组,各组34例,A组产妇宫口开至1 cm时采取罗哌卡因复合舒芬太尼硬膜外自控分娩镇痛,B组产妇宫口开至3 cm时采取罗哌卡因复合舒芬太尼硬膜外自控分娩镇痛,C组产妇未采取分娩镇痛,比较两组第一产程潜伏期、活跃期及第二产程持续时间及宫缩时视觉模拟评分(VAS)评分,比较各组产妇出血量、新生儿体质量及胎儿娩出后1 min、5 min Apgar评分,记录各组治疗30 d后不良反应。结果:A组、B组第一产程潜伏期持续时间明显较C组延长,活跃期持续时间较C组明显缩短,差异有统计学意义(P0.05);A组产妇宫颈口开至2 cm和cm时VAS评分低于B组和C组,差异有统计学意义(P0.05);A组、B组产妇在活跃期、第二产程时VAS评分低于C组,差异有统计学意义(P0.05);各组产妇出血量、新生儿体质量、Apgar评分比较均无统计学意义(P0.05);C组抑郁症发生率均高于较A组和B组,差异有统计学意义(P0.05)。结论:从产妇潜伏期开始应用罗哌卡因复合舒芬太尼进行分娩镇痛的效果较好,具有良好的应用价值。     

Nrk, an X-linked protein kinase in the germinal center kinase family, is required for placental development and fetoplacental induction of labor

The complete mechanism of labor induction in eutherian mammals remains unclear. Although important roles for the fetus and placenta in triggering labor have been proposed, no gene has been shown to be required in the fetus/placenta for labor induction. Here we show that Nrk, an X-linked gene encoding a Ser/Thr kinase of the germinal center kinase family, is essential in the fetus/placenta for labor in mice. Nrk was specifically expressed in the spongiotrophoblast layer, a fetus-derived region of the placenta, and Nrk disruption caused dysregulated overgrowth of the layer. Due to preferential inactivation of the paternally derived X chromosome in placenta, Nrk heterozygous mutant placentas exhibited a similar defect to that in Nrk-null tissues when the wild-type allele was paternally derived. However, the phenotype was weaker than in Nrk-null placentas due to leaky Nrk expression from the inactivated X chromosome. Crossing of Nrk-null females to wild-type and Nrk-null males, as well as uterine transfer of Nrk-null fetuses to wild-type females, revealed that pregnant mice exhibit a severe defect in delivery when all fetuses/placentas are Nrk-null. In addition, Nrk was not expressed in female reproductive tissues such as the uterus and ovary, as well as the fetal amnion and yolk sac, in pregnant mice. Progesterone and estrogen levels in the maternal circulation and placenta, which control the timing of labor, were unaffected upon Nrk disruption. We thus provide evidence for a novel labor-inducing fetoplacental signal that depends on the X chromosome and possibly arises from the placenta.     

Our better nature: Does resource stress predict beyond-household sharing?

Food sharing and (to a lesser extent) labor sharing play central roles in the evolution of cooperation literature. One popular explanation for sharing beyond the family is that it reduces the likelihood of shortages by pooling risk across households. However, the frequency and scope of sharing have never been systematically documented across nonindustrial societies, and the literature is driven by theoretical models, experimental games, and case studies among a few extensively-studied populations. Here we explore the cross-cultural context, frequency, and scope of food and labor sharing customs in relation to resource stress. Using ethnographic data from a worldwide sample of 98 societies in the Standard Cross-Cultural Sample (SCCS), we test the following hypotheses: 1) customary sharing of food and labor beyond the household are cultural universals, 2) societies subject to more resource stress (including unpredictable food-destroying natural hazards) will share more frequently, and 3) the more frequent the resource stress, the broader the geographic and social scope of sharing customs. Hypotheses 1 and 2 are generally supported and are consistent with the theory that extensive beyond-household sharing is adaptive in societies that are subject to more resource stress. Hypothesis 3 was not supported and, contrary to our predictions, there is suggestive evidence that sharing beyond-relatives may be attenuated when resource stress is high. In light of these findings, we consider how resource stress may constitute an important selection pressure for maintaining extensive cooperation and help to explain the ubiquity of beyond-household sharing.     

腰硬联合蛛网膜下腔注射芬太尼用于分娩镇痛的半数有效剂量的临床研究

目的:确定腰硬联合蛛网膜下腔注射芬太尼用于分娩镇痛的半数有效剂量(ED50),观察蛛网膜下腔注射半数有效剂量芬太尼的效果和副作用,并与蛛网膜下腔注射半数有效剂量的布比卡因进行对比。方法:首先,确定芬太尼用于分娩镇痛的半数有效剂量,筛选50例符合的产妇行腰硬联合分娩镇痛,蛛网膜下腔注射芬太尼的剂量始于25μg,如果镇痛有效,下一病例减少2.5μg芬太尼;如果无效则下一病例增加2.5μg芬太尼。用Probit回归分析计算芬太尼蛛网膜下腔注射行分娩镇痛的半数有效剂量和95%可信区间(95%CI)。第二步,筛选100例需要进行分娩镇痛的产妇,随机分入ED50芬太尼组(F组)和ED50布比卡因组(B组),比较两组药物镇痛效果及起效时间、产妇下肢运动阻滞程度及血压心率变化、胎心变化和镇痛全程药物追加次数。结果:芬太尼蛛网膜下腔注射分娩镇痛的ED50为11.5μg,95%CI为3.5-15.4μg。F组镇痛的平均起效时间为(12.0±3.8)min,两组镇痛的成功率没有统计学差异(P=0.218),F组需要追加PCA的病例百分率明显少于B组(P=0.018)。F组下肢运动阻滞程度轻于B组(P=0.018)。两组镇痛方法对产妇的血压、心率均无明显影响。两组胎心下降的发生率没有明显差异(P0.05)。F组皮肤瘙痒的发生率明显增加(P=0.000)。结论:腰硬联合分娩镇痛蛛网膜下腔注射芬太尼的ED50为11.5μg,95%CI为3.5-15.4μg。蛛网膜下腔注射半数有效剂量的芬太尼可以提供简便、持久、满意和安全的镇痛效果,并且对下肢运动阻滞程度较小,但其所致皮肤瘙痒的发生率升高。     

“A carnival of promiscuous carnal indulgence”: bureaucrats’ ambivalence in reconciling capitalist production with native American habitus

In 1921 the U.S. Office of Indian Affairs (OIA) attempted to suppress ritual public performances in the Southwestern Pueblos. Several reams of documenting text were used to support this authorizing text. These documenting texts were affidavits purporting to describe “degrading tendencies” and “immoral relations” in the Puebloan habitus. The OIA used these sensationalized representations of the habitus of Native Americans’ communities to promote and justify the policy of forced acculturation in the waning days of its implementation. What is perplexing is that these supporting texts were trotted out so late, decades after the major thrusts of the forced acculturation program had first been put into play. My purpose is to analyze the place of these texts in the forced acculturation program. I suggest, following Anne McClintock (1995) that the obsessive fascination that the public performances seem to have held for those who reported on and condemned them, represent a layered and complex intertwining of ambivalence about domestic social relations and gender with confusion about culture and labor. Examining a slice of the U.S. Government’s policy of forced acculturation in a corner of the Native American world reveals a potentially implosive anxiety of reconciling the imposition of a desired mode of production with the persistence of a habitus perceived as celebrating the violation of appropriate domesticity.

A Novel Biased Allosteric Compound Inhibitor of Parturition Selectively Impedes the Prostaglandin F2α-mediated Rho/ROCK Signaling Pathway

The prostaglandin F2α (PGF2α) receptor (FP) is a key regulator of parturition and a target for pharmacological management of preterm labor. However, an incomplete understanding of signaling pathways regulating myometrial contraction hinders the development of improved therapeutics. Here we used a peptidomimetic inhibitor of parturition in mice, PDC113.824, whose structure was based on the NH₂-terminal region of the second extracellular loop of FP receptor, to gain mechanistic insight underlying FP receptor-mediated cell responses in the context of parturition. We show that PDC113.824 not only delayed normal parturition in mice but also that it inhibited both PGF2α- and lipopolysaccharide-induced preterm labor. PDC113.824 inhibited PGF2α-mediated, Gα₁₂-dependent activation of the Rho/ROCK signaling pathways, actin remodeling, and contraction of human myometrial cells likely by acting as a non-competitive, allosteric modulator of PGF2α binding. In contrast to its negative allosteric modulating effects on Rho/ROCK signaling, PDC113.824 acted as a positive allosteric modulator on PGF2α-mediated protein kinase C and ERK1/2 signaling. This bias in receptor-dependent signaling was explained by an increase in FP receptor coupling to Gα_q, at the expense of coupling to Gα₁₂. Our findings regarding the allosteric and biased nature of PDC113.824 offer new mechanistic insights into FP receptor signaling relevant to parturition and suggest novel therapeutic opportunities for the development of new tocolytic drugs.