BACKGROUND & AIMS: :Laminin 5/laminin 332 (LN332) is an adhesion substrate for epithelial cells. After secretion of LN332, a regulated cleavage occurs at the carboxy-terminus of its alpha3 subunit, which releases a tandem of two globular modules named LG4/5. We show that the presence of the LG4/5 domain in precursor LN332 decreases its integrin-mediated cell adhesion properties in comparison with mature LN332. Whereas cell adhesion to the recombinant LG4/5 fragment relies solely on the heparan sulfate proteoglycan (HSPG) receptor syndecan-1, we reveal that both syndecan-1 and the alpha3beta1 integrin bind to precursor LN332. We further demonstrate that syndecan-1 mediated cell adhesion to the LG4/5 fragment and pre-LN332 allows the formation of fascin-containing protrusions, depending on the GTPases Rac and Cdc42 activation. Reducing syndecan-1 expression in normal keratinocytes prevents cell protrusions on pre-LN332 with subsequent failure of the peripheral localization of the alpha3beta1 integrin. We finally show that cell migration on pre-LN332 requires syndecan-1. Therefore, the LG4/5 domain in precursor LN332 appears to trigger intracellular signaling events, which participate in keratinocyte motility.

背景与目标： ：层粘连蛋白5 /层粘连蛋白332（LN332）是上皮细胞的粘附底物。 LN332分泌后，在其alpha3亚基的羧基末端发生有规律的切割，释放出串联的两个球形模块LG4 / 5。我们显示，与成熟的LN332相比，前体LN332中LG4 / 5域的存在降低了其整合素介导的细胞粘附特性。尽管细胞对重组LG4 / 5片段的粘附仅依赖于硫酸乙酰肝素蛋白聚糖（HSPG）受体syndecan-1，但我们发现syndecan-1和alpha3beta1整联蛋白均与前体LN332结合。我们进一步证明了syndecan-1介导的细胞粘附到LG4 / 5片段和pre-LN332允许形成含有fascin的突起，具体取决于GTPa​​ses Rac和Cdc42的激活。减少正常角质形成细胞中syndecan-1的表达可以防止pre-LN332上的细胞突出，并随后导致alpha3beta1整联蛋白的外周定位失败。我们最终证明，前LN332上的细胞迁移需要syndecan-1。因此，前体LN332中的LG4 / 5结构域似乎触发了细胞内信号传导事件，该事件参与了角质形成细胞的运动。

BACKGROUND & AIMS: :By interrupting the integrity of the systemic and renal renin-angiotensin system, angiotensin-converting enzyme inhibitors have been shown, experimentally, to preferentially reduce postglomerular capillary arteriolar resistance, to reduce glomerular capillary pressure, and to increase the ultrafiltration coefficient. Under normal physiological conditions, angiotensin-converting enzyme inhibitors have little effect on glomerular filtration rate; however, they increase effective renal plasma flow at renal perfusion pressures within the normal autoregulatory range and renal vascular resistance is decreased. In contrast, calcium antagonists have been shown, experimentally, to preferentially reduce preglomerular capillary arteriolar resistance. Their effects on angiotensin II and postglomerular capillary arteriolar resistance (hence, glomerular capillary pressure and the ultrafiltration coefficient) are controversial. Under normal physiological conditions, calcium antagonists increase both glomerular filtration rate and effective renal plasma flow at renal perfusion pressures within the normal autoregulatory range and renal vascular resistance is decreased. In patients with essential hypertension, studies have demonstrated that angiotensin-converting enzyme inhibitors (as predicted) sustain glomerular filtration rate, increase effective renal plasma flow, and decrease renal vascular resistance. However, essential hypertensive patients with impaired glomerular filtration rate may demonstrate marked improvement in both glomerular filtration rate and effective renal plasma flow. Calcium antagonists (as predicted) may increase both glomerular filtration rate and effective renal plasma flow (at high renal perfusion pressures) and may decrease renal vascular resistance. Calcium antagonists may also improve both glomerular filtration rate and effective renal plasma flow in patients with impaired glomerular filtration rate. Long-term clinical trials comparing the renal effects of angiotensin-converting enzyme inhibitors with those of calcium antagonists in essential hypertensive patients have not been reported. It remains to be determined if the potentially different effects of these two classes of antihypertensive drugs on the renal microcirculation do or do not translate into different renal protective advantages to patients at risk for the development and/or progression of hypertensive nephrosclerosis.

背景与目标： 通过实验证明，通过破坏全身和肾脏的肾素-血管紧张素系统的完整性，血管紧张素转化酶抑制剂可优先降低肾小球毛细血管小动脉阻力，降低肾小球毛细血管压力，并增加超滤系数。在正常的生理条件下，血管紧张素转化酶抑制剂对肾小球滤过率的影响很小。但是，它们在正常自我调节范围内的肾脏灌注压力下会增加有效的肾脏血浆流量，并且肾血管阻力降低。相反，实验表明，钙拮抗剂可优先降低肾小球前毛细血管的阻力。它们对血管紧张素II和肾小球后毛细血管小动脉阻力（因此，肾小球毛细血管压力和超滤系数）的影响是有争议的。在正常生理条件下，钙拮抗剂在正常自动调节范围内的肾脏灌注压力下会增加肾小球滤过率和有效肾血浆流量，并且肾血管阻力降低。在原发性高血压患者中，研究表明，血管紧张素转化酶抑制剂（如预期的那样）可维持肾小球滤过率，增加有效肾血浆流量并降低肾血管阻力。然而，肾小球滤过率受损的原发性高血压患者可能表现出肾小球滤过率和有效肾血浆流量的明显改善。钙拮抗剂（如预期的那样）可能会增加肾小球滤过率和有效的肾血浆流量（在高肾灌注压力下），并且可能会降低肾血管阻力。对于肾小球滤过率受损的患者，钙拮抗剂还可以改善肾小球滤过率和有效的肾血浆流量。尚未有长期临床试验比较血管紧张素转化酶抑制剂与钙拮抗剂在基本高血压患者中的肾脏作用。这两类降压药对肾脏微循环的潜在不同作用是否会转化为对患有高血压肾硬化发展和/或进展风险的患者的不同肾脏保护优势，尚待确定。

BACKGROUND & AIMS: :Our previous studies have suggested a role for AMP-activated protein kinase (AMPK) in the induction of CYP2B6 by phenobarbital (PB) in hepatoma-derived cells (Rencurel et al., 2005). In this study, we showed in primary human hepatocytes that: 1) 5'-phosphoribosyl-5-aminoimidazol-4-carboxamide 1-beta-d-ribofuranoside and the biguanide metformin, known activators of AMPK, dose-dependently increase the expression of CYP2B6 and CYP3A4 to an extent similar to that of PB. 2) PB, but not the human nuclear receptor constitutive active/androstane receptor (CAR) ligand 6-(4-chlorophenyl)imidazol[2,1-6][1,3]thiazole-5-carbaldehyde, dose-dependently increase AMPK activity. 3) Pharmacological inhibition of AMPK activity with compound C or dominant-negative forms of AMPK blunt the inductive response to phenobarbital. Furthermore, in transgenic mice with a liver-specific deletion of both the alpha1 and alpha2 AMPK catalytic subunits, basal levels of Cyp2b10 and Cyp3a11 mRNA were increased but not in primary culture of mouse hepatocytes. However, phenobarbital or 1,4 bis[2-(3,5-dichloropyridyloxy)]benzene, a mouse CAR ligand, failed to induce the expression of these genes in the liver or cultured hepatocytes from mice lacking hepatic expression of the alpha1 and alpha2 subunits of AMPK. The distribution of CAR between the nucleus and cytosol was not altered in hepatocytes from mice lacking both AMPK catalytic subunits. These data highlight the essential role of AMPK in the CAR-mediated signal transduction pathway.

背景与目标： ：我们先前的研究表明，AMP激活的蛋白激酶（AMPK）在苯巴比妥（PB）诱导肝癌衍生细胞中诱导CYP2B6的作用（Rencurel et al。，2005）。在这项研究中，我们在原代人肝细胞中显示：1）5'-磷酸核糖基-5-氨基咪唑-4羧酰胺1-β-d-核呋喃糖苷和双胍二甲双胍（AMPK的已知激活剂）剂量依赖性地增加了AMPK的表达。 CYP2B6和CYP3A4的程度与PB相似。 2）PB，而不是人核受体组成型活性/雄烷受体（CAR）配体6-（4-氯苯基）咪唑[2,1-6] [1,3]噻唑-5-甲醛，剂量依赖性地增加AMPK活动。 3）用化合物C或显性阴性形式的AMPK抑制AMPK活性的药理作用减弱了对苯巴比妥的诱导反应。此外，在具有肝脏特异性α1和α2AMPK催化亚基缺失的转基因小鼠中，Cyp2b10和Cyp3a11 mRNA的基础水平增加了，但在小鼠肝细胞的原代培养中却没有。但是，苯巴比妥或小鼠CAR配体1,4双[2-（3,5-二氯吡啶氧基）]苯不能诱导这些基因在肝脏或培养的肝细胞中表达，而这些小鼠缺乏肝表达α1和α2的小鼠AMPK的亚基。在缺少两个AMPK催化亚基的小鼠的肝细胞中，CAR在细胞核和细胞质之间的分布没有改变。这些数据突出了AMPK在CAR介导的信号转导途径中的重要作用。

BACKGROUND & AIMS: :Piwi (P-element induced wimpy testis) is an important gene involved in stem cell maintenance and gametogenesis in vertebrates. However, in most invertebrates, especially mollusks, the function of Piwi during gametogenesis remains largely unclear. To further understand the function of Piwi during gametogenesis, full-length cDNA of Piwi1 from scallop Chlamys farreri (Cf-Piwi1) was characterized, which consisted of a 2,637 bp open reading frame encoding an 878-amino acid protein. Cf-Piwi1 mRNA was mainly localized in the spermatogonia, spermatocytes, oogonia, oocytes of early development and intra-gonadal somatic cells. Additionally, the knockdown of Cf-Piwi1 by injection of Cf-Piwi1-dsRNA (double-stranded RNA) into scallop adductor led to a loss of germ cells in C. farreri gonads. Apoptosis was observed mainly in spermatocytes and oocytes of early development, as well as in a small number of spermatogonia and oogonia. Our findings indicate that Cf-Piwi1 is essential for gametogenesis in the scallop C. farreri.

背景与目标： ：Piwi（P元素诱导的w弱睾丸）是一个重要的基因，参与脊椎动物的干细胞维持和配子发生。但是，在大多数无脊椎动物中，尤其是软体动物中，Piwi在配子发生过程中的功能仍然不清楚。为了进一步了解Piwi在配子发生过程中的功能，对扇贝衣原体（Cf-Piwi1）的Piwi1全长cDNA（Cf-Piwi1）进行了表征，该cDNA包含一个2,637 bp的开放阅读框，编码878个氨基酸。 Cf-Piwi1 mRNA主要位于精原细胞，精细胞，卵子，早期发育的卵母细胞和性腺内的体细胞中。此外，通过将Cf-Piwi1-dsRNA（双链RNA）注入扇贝加合物中来敲低Cf-Piwi1导致法氏梭菌性腺中生殖细胞的损失。细胞凋亡主要在早期发育的精母细胞和卵母细胞中观察到，在少数精原细胞和卵母细胞中也观察到。我们的发现表明，Cf-Piwi1对于扇贝C. farreri的配子发生至关重要。

BACKGROUND & AIMS: :The identification of essential proteins in protein-protein interaction (PPI) networks is of great significance for understanding cellular processes. With the increasing availability of large-scale PPI data, numerous centrality measures based on network topology have been proposed to detect essential proteins from PPI networks. However, most of the current approaches focus mainly on the topological structure of PPI networks, and largely ignore the gene ontology annotation information. In this paper, we propose a novel centrality measure, called TEO, for identifying essential proteins by combining network topology, gene expression profiles, and GO information. To evaluate the performance of the TEO method, we compare it with five other methods (degree, betweenness, NC, Pec, and CowEWC) in detecting essential proteins from two different yeast PPI datasets. The simulation results show that adding GO information can effectively improve the predicted precision and that our method outperforms the others in predicting essential proteins.

背景与目标： ：蛋白质-蛋白质相互作用（PPI）网络中必需蛋白质的鉴定对理解细胞过程具有重要意义。随着大规模PPI数据可用性的提高，已经提出了许多基于网络拓扑的集中度检测方法来检测PPI网络中的必需蛋白。但是，当前大多数方法主要集中在PPI网络的拓扑结构上，而在很大程度上忽略了基因本体注释信息。在本文中，我们提出了一种新的集中度度量，称为TEO，它通过结合网络拓扑，基因表达谱和GO信息来鉴定必需蛋白质。为了评估TEO方法的性能，我们将其与其他五种方法（度，中间性，NC，Pec和CowEWC）进行比较，以检测来自两个不同酵母PPI数据集的必需蛋白质。仿真结果表明，添加GO信息可以有效地提高预测精度，并且我们的方法在预测必需蛋白质方面优于其他方法。

BACKGROUND & AIMS: :For 17 years, the Blauth total knee prosthesis has been implanted with its basic constructional features remaining unchanged. While it is true that the prosthetic components are constrained by a mechanical hinge, load transmission is actually effected in accordance with the low-friction principle through the cup-shaped condylar surfaces. Packing of the prosthesis in the bone is ensured by large load-bearing surfaces and by specific elements intended for rotational stability. In a comprehensive follow-up review, 497 implants were studied over a period of one to 15 years (average, 45 months). Aseptic loosening occurred in only 1.2% of the prostheses, and deep infection was found in 3% of the patients in the follow-up review. According to survival statistics, the probability of finding prostheses without deep infection or loosening after more than ten years is 89%. The efficiency of total knee arthroplasty (TKA) by hinged prostheses should therefore not be judged by the results obtained with the pioneer implants, which date back to the beginnings of TKA. The clinical results obtained clearly demonstrate that there is 90 degrees knee flexion in more than 88% of the implants. A subjective appraisal demonstrated substantially less pain compared with the preoperative findings. Problems originating from the patella were recorded in less than 10%. However, in 1985, an improved prosthetic design was introduced that also provided for the replacement of the posterior surface of the patella and for a proximally extended patellar bearing. The position of the hinge and implant packing remained unchanged. The results obtained so far with the modified prosthetic design are very good.

背景与目标： ：17年来，Blauth全膝关节假体已被植入，其基本结构特征保持不变。虽然假肢部件确实受机械铰链约束，但实际上是根据低摩擦原理通过杯状con表面实现了载荷传递。假体在骨头中的堆积可通过较大的承重表面和用于旋转稳定性的特定元件来确保。在全面的随访评估中，在1至15年（平均45个月）的时间内对497个植入物进行了研究。在随访检查中，仅1.2％的假体发生了无菌性松动，而3％的患者中发现了深部感染。根据生存统计，超过十年后发现没有深层感染或松动的假体的可能性为89％。因此，不应通过先驱植入物获得的结果来判断铰接式假体进行的全膝关节置换术（TKA）的效率，这可以追溯到TKA的开始。获得的临床结果清楚地表明，超过88％的植入物有90度的膝盖弯曲。与术前相比，主观评估显示疼痛明显减轻。 recorded骨引起的问题少于10％。然而，在1985年，引入了改进的假体设计，该假体设计还提供了the骨后表面的替换和向近侧延伸的tell骨轴承。铰链和植入物填充物的位置保持不变。到目前为止，使用改良的假体设计所获得的结果非常好。

BACKGROUND & AIMS: :Brown adipose tissue (BAT) increases energy expenditure and is an attractive therapeutic target for obesity. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), an amplifier of local glucocorticoid activity, has been shown to modulate white adipose tissue (WAT) metabolism and function. In this study, we investigated the roles of 11β-HSD1 in regulating BAT function. We observed a significant increase in the expression of BAT-specific genes, including UCP1, Cidea, Cox7a1, and Cox8b, in BVT.2733 (a selective inhibitor of 11β-HSD1)-treated and 11β-HSD1-deficient primary brown adipocytes of mice. By contrast, a remarkable decrease in BAT-specific gene expression was detected in brown adipocytes when 11β-HSD1 was overexpressed, which effect was reversed by BVT.2733 treatment. Consistent with the in vitro results, expression of a range of genes related to brown fat function in high-fat diet-fed mice treated with BVT.2733. Our results indicate that 11β-HSD1 acts as a vital regulator that controls the expression of genes related to brown fat function and as such may become a potential target in preventing obesity.

背景与目标： ：棕色脂肪组织（BAT）增加能量消耗，并且是肥胖症的诱人治疗靶标。 11β-羟基类固醇脱氢酶1（11β-HSD1）是一种局部糖皮质激素活性的放大器，已被证明可调节白色脂肪组织（WAT）的代谢和功能。在这项研究中，我们调查了11β-HSD1在调节BAT功能中的作用。我们观察到在BVT.2733（11β-HSD1的选择性抑制剂）治疗和小鼠缺乏11β-HSD1的原代棕色脂肪细胞中，BAT特异性基因（包括UCP1，Cidea，Cox7a1和Cox8b）的表达显着增加。相比之下，当11β-HSD1过表达时，褐色脂肪细胞中BAT特异性基因表达显着下降，这种作用被BVT.2733处理所逆转。与体外结果一致，在用BVT.2733处理的高脂饮食喂养小鼠中，一系列与棕色脂肪功能有关的基因的表达。我们的结果表明，11β-HSD1可以作为重要的调节剂，控制与棕色脂肪功能相关的基因的表达，因此可能成为预防肥胖的潜在靶标。

BACKGROUND & AIMS: :Chronic administration of nadolol has been reported to reduce blood pressure either without or with a concomitant fall of renal blood flow. We therefore studied the effects of nadolol 80 mg once daily on ambulatory blood pressure, renal and systemic haemodynamics in patients with mild to moderate essential hypertension. Ten patients took part in this randomized, double-blind, placebo-controlled, crossover study, each phase of which lasted 4 weeks. Nadolol significantly reduced ambulatory blood pressure and heart rate, but had no effect on blood pressure variability. Cardiac output was significantly reduced by nadolol and total peripheral resistance increased but without reaching statistical significance. Despite the fall in blood pressure and cardiac output, renal blood flow and glomerular filtration rate remained unchanged. The fraction of cardiac output reaching the kidneys rose significantly and renal vascular resistance was significantly reduced. Body weight, urinary sodium excretion and urine flow rate remained unchanged. We conclude that nadolol 80 mg once daily lowers ambulatory blood pressure in patients with mild to moderate hypertension without impairment of renal blood flow, indicating a redistribution of cardiac output to the kidneys. The mechanism of the renal vasodilator effect of nadolol remains to be determined.

背景与目标： ：有报道称，长期服用萘多洛可降低血压，既不伴有肾血流下降，也可伴有肾血流下降。因此，我们研究了纳多洛尔80 mg每天一次对轻度至中度原发性高血压患者动态血压，肾脏和全身血流动力学的影响。十名患者参加了这项随机，双盲，安慰剂对照，交叉研究，其每个阶段持续4周。纳多洛尔显着降低了门诊血压和心率，但对血压变异性没有影响。萘多洛尔可显着降低心输出量，总外周阻力增加，但未达到统计学意义。尽管血压和心输出量下降，但肾血流量和肾小球滤过率保持不变。到达肾脏的心输出量比例显着上升，肾血管阻力显着降低。体重，尿钠排泄和尿流率保持不变。我们得出的结论是，纳多洛尔80 mg每天一次可降低轻度至中度高血压患者的门诊血压，而不会损害肾血流量，这表明心输出量会重新分配给肾脏。纳多洛尔的肾血管舒张作用机制尚待确定。

BACKGROUND & AIMS: OBJECTIVE:To assess whether the implementation of a package of activities through the joint action of the three international healthcare professionals associations (HCPAs) increased the use of intrapartum and postnatal essential interventions (EIs) in two hospitals in Uganda. METHODS:A non-controlled before-and-after study was undertaken to evaluate the effect of a package of activities designed to change practice relating to nine EIs among providers. Coverage of the EIs was measured in a 3-month pre-implementation period and a 3-month post-implementation period in 2014. Data were obtained for women older than 18 years who delivered vaginally or by cesarean. RESULTS:Overall, 4816 women were included. Level of use remained high for EIs used widely at baseline. Some EIs that had low use at baseline did not show improvement after the implementation. Promotion of breastfeeding showed a significant improvement in the Kampala hospital, from 8.5% (8/94) to 25.6% (30/117; P=0.001), whereas promotion of hygiene in cord care improved at the Mbarara hospital, from 0.1% (2/1592) to 46.0% (622/1351; P<0.001). CONCLUSION:These exploratory results show that a package delivered through the joint work of the three HCPAs was feasible to implement along with rigorous data collection. Although the data show disparities, trends suggest that improvement could be achieved.

背景与目标： 目的：评估通过三个国际卫生保健专业人员协会（HCPA）的联合行动实施一揽子活动是否增加了乌干达两所医院的产前和产后基本干预措施（EI）的使用。
方法：进行了一项非对照的前后研究，以评估旨在改变提供者之间与9个EI相关的实践的一揽子活动的效果。在2014年的实施前3个月和实施后3个月期间测量了EI的覆盖范围。获得了18岁以上通过阴道或剖宫产分娩的女性的数据。
结果：总共包括4816名女性。在基线广泛使用的EI的使用水平仍然很高。某些在基线使用量很少的EI在实施后并未显示出改善。促进母乳喂养在坎帕拉医院显示出显着改善，从8.5％（8/94）提高到25.6％（30/117； P = 0.001），而在姆巴拉拉医院改善了脐带护理的卫生，从0.1％（ 2/1592）至46.0％（622/1351； P <0.001）。
结论：这些探索性结果表明，通过三个HCPA的联合工作提供的一揽子计划与严格的数据收集一起是可行的。尽管数据显示出差异，但趋势表明可以实现改善。

BACKGROUND & AIMS: :Reports of randomized controlled trials (RCTs) inform the care of future patients and are especially important to clinicians and systematic reviewers. Readers should satisfy themselves that the study methods were sound. Clinicians should consider the relevance to their own patients, both benefits and harms, and absolute as well as relative effects. Trial reports should provide a clear, transparent, and complete report of what was done and what was found. Unfortunately, bad reporting of RCTs is common, which has serious consequences for clinical practice, research, policy making, and ultimately for patients. RCT reports should adhere to the CONSORT Statement, a minimum set of items that should be addressed. Authors, peer reviewers, and editors should all work to ensure that research reports maximize the value derived from the cost and effort of conducting a trial.

背景与目标： ：随机对照试验（RCT）的报告可为将来的患者提供护理，对临床医生和系统评价者尤为重要。读者应使自己满意，认为研究方法是正确的。临床医生应考虑与他们自己患者的相关性，既包括利弊，也包括绝对效果和相对效果。试用报告应提供有关所做的工作和发现的内容的清晰，透明和完整的报告。不幸的是，RCT的不良报告很常见，这对临床实践，研究，政策制定乃至最终对患者都有严重的后果。 RCT报告应遵守CONSORT声明，这是应处理的最低限度的一组项目。作者，同行审稿人和编辑都应努力确保研究报告从进行试验的成本和努力中获得最大的价值。

BACKGROUND & AIMS: :Integrin-linked kinase (ILK) has been implicated in the pathogenesis of proteinuria and congenital nephrotic syndrome. However, the function of ILK in glomerular podocyte in a physiologic setting remains unknown. In this study, a mouse model was generated in which ILK gene was selectively disrupted in podocytes by using the Cre-LoxP system. Podocyte-specific ablation of ILK resulted in heavy albuminuria, glomerulosclerosis, and kidney failure, which led to animal death beginning at 10 wk of age. Podocyte detachment and apoptosis were not observed at 4 wk of age, when albuminuria became prominent, indicating that they are not the initial cause of proteinuria. Electron microscopy revealed an early foot process effacement, as well as morphologic abnormality, in ILK-deficient podocytes. ILK deficiency caused an aberrant distribution of nephrin and alpha-actinin-4 in podocytes, whereas the localization of podocin and synaptopodin remained relatively intact. Co-immunoprecipitation demonstrated that ILK physically interacted with nephrin to form a ternary complex, and alpha-actinin-4 participated in ILK/nephrin complex formation. Therefore, ILK plays an essential role in specifying nephrin and alpha-actinin-4 distribution and in maintaining the slit diaphragm integrity and podocyte architecture. These results also illustrate that the integrin and slit diaphragm signals in podocytes are intrinsically coupled through an ILK-dependent mechanism.

背景与目标： 整联蛋白连接激酶（ILK）已被证明与蛋白尿和先天性肾病综合征的发病机制有关。然而，在生理环境中ILK在肾小球足细胞中的功能仍是未知的。在这项研究中，生成了小鼠模型，其中使用Cre-LoxP系统选择性地破坏了足细胞中的ILK基因。 ILK的足细胞特异性消融导致严重的蛋白尿，肾小球硬化和肾衰竭，从而导致动物从10周龄开始死亡。当蛋白尿变得突出时，在4周龄时未观察到足细胞脱离和凋亡，这表明它们不是蛋白尿的最初原因。电子显微镜检查显示，ILK缺陷足细胞有早期足突消失和形态异常。 ILK缺乏引起足细胞中nephrin和α-actinin-4的异常分布，而podocin和synaptopodin的定位仍然相对完整。免疫共沉淀表明ILK与nephrin物理相互作用形成三元复合物，而alpha-actinin-4参与了ILK / nephrin复合物的形成。因此，ILK在指定nephrin和α-actinin-4分布以及维持缝隙隔膜完整性和足细胞结构方面起着至关重要的作用。这些结果还表明，足细胞中的整联蛋白和裂膜信号是通过ILK依赖性机制固有地偶联的。

BACKGROUND & AIMS: :The aim of this work is to evaluate the stability and release of chitosan beads loaded with volatile molecules of Mentha piperita essential oil (E.O.) in a cosmetic formulation. The ability of the beads to quickly release Mentha piperita E.O. during use of a cosmetic formulation such as a bath foam is also assessed. The chitosan beads were produced with three different chitosan dispersions gelled with two different gelling solutions: (a) a 10% solution of sodium hydroxide (NaOH) and (b) a 4% solution of sodium tripolyphosphate (TPP). A few properties of six bead samples loaded with Mentha piperita E.O. are assessed. The properties are morphology, size, swelling ability, encapsulation efficiency, stability in time, and fast release of Mentha piperita E.O. during the use phase of the cosmetic formulation.

背景与目标： ：这项工作的目的是评估化妆品配方中负载有薄荷醇薄荷油（E.O.）挥发性分子的壳聚糖珠的稳定性和释放。珠子迅速释放薄荷薄荷E.O.的能力还评估了在使用化妆品配方（例如沐浴泡沫）的过程中。用三种不同的壳聚糖分散体和两种不同的胶凝溶液凝胶化制备了壳聚糖珠子：（a）10％的氢氧化钠（NaOH）溶液和（b）4％的三聚磷酸钠（TPP）溶液。负载有薄荷（Mentha piperita E.O.）的六个珠子样品的一些性能被评估。这些特性是薄荷醇（Mentha piperita E.O）的形态，大小，溶胀能力，包封效率，时间稳定性和快速释放性。在化妆品配方的使用阶段。

BACKGROUND & AIMS: :Much of the peripheral nervous system of the head is derived from ectodermal thickenings, called placodes, that delaminate or invaginate to form cranial ganglia and sense organs. The trigeminal ganglion, which arises lateral to the midbrain, forms via interactions between the neural tube and adjacent ectoderm. This induction triggers expression of Pax3, ingression of placode cells and their differentiation into neurons. However, the molecular nature of the underlying signals remains unknown. Here, we investigate the role of PDGF signaling in ophthalmic trigeminal placode induction. By in situ hybridization, PDGF receptor beta is expressed in the cranial ectoderm at the time of trigeminal placode formation, with the ligand PDGFD expressed in the midbrain neural folds. Blocking PDGF signaling in vitro results in a dose-dependent abrogation of Pax3 expression in recombinants of quail ectoderm with chick neural tube that recapitulate placode induction. In ovo microinjection of PDGF inhibitor causes a similar loss of Pax3 as well as the later placodal marker, CD151, and failure of neuronal differentiation. Conversely, microinjection of exogenous PDGFD increases the number of Pax3+ cells in the trigeminal placode and neurons in the condensing ganglia. Our results provide the first evidence for a signaling pathway involved in ophthalmic (opV) trigeminal placode induction.

背景与目标： ：头部的大部分周围神经系统来自表皮增厚，称为斑块，可分层或渐渐形成颅神经节和感觉器官。三叉神经节出现在中脑外侧，是通过神经管和相邻外胚层之间的相互作用而形成的。这种诱导触发Pax3的表达，placode细胞的进入及其分化为神经元。但是，基本信号的分子性质仍然未知。在这里，我们调查PDGF信号在眼科三叉戟斑块诱导中的作用。通过原位杂交，PDGF受体β在三叉神经板形成时在颅外胚层表达，配体PDGFD在中脑神经折叠处表达。在体外阻断PDGF信号传导会导致鹌鹑外胚层重组体与雏鸡神经管重现斑块诱导，Pax3表达呈剂量依赖性消除。在卵内，PDGF抑制剂的显微注射会导致Pax3以及以后的斑状标记物CD151的相似损失，并导致神经元分化失败。相反，显微注射外源性PDGFD会增加三叉戟斑节中Pax3细胞的数量，以及浓缩神经节中神经元的数量。我们的研究结果为涉及眼科（opV）三叉神经基板诱导信号通路的第一个证据。

BACKGROUND & AIMS: BACKGROUND:Harmane (1-methyl-9H-pyrido[3,4-b]indole), a neurotoxin, may be an environmental risk factor for essential tremor (ET). Harmane and related chemicals are toxic to the cerebellum. Whether it is through this mechanism (cerebellar toxicity) that harmane leads to ET is unknown. Impaired olfaction may be a feature of cerebellar disease. OBJECTIVE:To determine whether blood harmane concentrations correlate with olfactory test scores in patients with ET. METHODS:Blood harmane concentrations were quantified using high performance liquid chromatography. Odor identification testing was performed with the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS:In 83 ET cases, higher log blood harmane concentration was correlated with lower UPSIT score (rho=-0.46, p<0.001). 25/40 (62.5%) cases with high log blood harmane concentration (based on a median split) had low UPSIT scores (based on a median split) vs. 12/43 (27.9%) ET cases with low log blood harmane concentration (adjusted odd ratios (OR) 4.04, 95% confidence intervals (CI) 1.42-11.50, p=0.009). When compared with the low log blood harmane tertile, the odds of olfactory dysfunction were 2.64 times higher in cases in the middle tertile and 10.95 times higher in cases in the high tertile. In 69 control subjects, higher log blood harmane concentration was not correlated with lower UPSIT score (rho=0.12, p=0.32). CONCLUSIONS:Blood harmane concentrations were correlated with UPSIT scores in ET cases but not controls. These analyses set the stage for postmortem studies to further explore the role of harmane as a cerebellar toxin in ET.

背景与目标： 背景：Harmane（1-甲基-9H-吡啶并[3,4-b]吲哚）是一种神经毒素，可能是原发性震颤（ET）的环境危险因素。 Harmane和相关化学物质对小脑有毒。烷烃是否通过这种机制（小脑毒性）导致ET尚不清楚。嗅觉障碍可能是小脑疾病的特征。
目的：确定ET患者血液中的烷烃含量是否与嗅觉测试成绩相关。
方法：采用高效液相色谱法定量测定甲醛的血中烷烃浓度。气味识别测试是通过宾夕法尼亚大学气味识别测试（UPSIT）进行的。
结果：在83例ET患者中，较高的对数血液harmane浓度与较低的UPSIT评分相关（rho = -0.46，p <0.001）。 25/40（62.5％）的高对数血液harmane浓度（基于中位数拆分）病例的UPSIT得分较低（基于中位数的分裂），而12/43（27.9％）的ET血液血液harmane浓度较低的病例（27.9％）调整后的奇数比（OR）4.04，95％置信区间（CI）1.42-11.50，p = 0.009）。与低对数血液harmane三分位数相比，中三分位数的患者嗅觉功能障碍的几率高2.64倍，高三分位数的患者嗅觉功能障碍的几率高10.95倍。在69名对照受试者中，较高的log血液harmane浓度与较低的UPSIT得分无关（rho = 0.12，p = 0.32）。
结论：ET病例的血液中甲醛含量与UPSIT评分相关，而与对照组无关。这些分析为进行死后研究奠定了基础，以进一步探讨harmane作为ET中小脑毒素的作用。

BACKGROUND & AIMS: BACKGROUND:Many factors have been implicated in the pathogenesis of unexplained recurrent spontaneous abortion (URSA). The current study was conducted to determine the possible role of antioxidant status and tumor necrosis factor-alpha (TNF-alpha) in URSA. METHODS:Reduced glutathione (GSH), glutathione reductase (GSH-R), glutathione peroxidase (GSH-PX), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), malondialdehyde (MDA) and TNF-alpha were assayed in women suffering unexplained first-trimester abortions. Two groups were included, the first represented by 24 women with URSA (number of abortions 3-5) and the second included 16 women with URSA (number of abortions >5). The control group included 20 women within their first trimester of pregnancy and 20 non-pregnant healthy females within their follicular phase. RESULTS:We observed that the antioxidant levels measured were significantly lower in URSA groups than in the control group (p<0.05 for each comparison). Higher TNF-alpha, MDA and NO production were detected in URSA groups compared to controls (p<0.05 for each comparison). URSA 3-5 was associated with significantly higher levels of antioxidants and lower levels of TNF-alpha compared to levels in URSA >5. CONCLUSIONS:Impaired antioxidant defense and an increase in oxidative reactive species may be responsible for recurrent abortion due to possible damage produced by their generation. In addition, the level of TNF-alpha apparently contributes to the pathogenesis of URSA.

背景与目标： 背景：许多因素与无法解释的反复自然流产（URSA）的发病机制有关。进行当前的研究以确定抗氧化剂状态和肿瘤坏死因子-α（TNF-α）在URSA中的可能作用。
方法：还原型谷胱甘肽（GSH），谷胱甘肽还原酶（GSH-R），谷胱甘肽过氧化物酶（GSH-PX），过氧化氢酶（CAT），超氧化物歧化酶（SOD），一氧化氮（NO），丙二醛（MDA）和TNF-α在无法解释的早孕流产妇女中进行了检测。包括两组，第一组由24名URSA妇女（流产次数3-5）代表，第二组包括16名URSA妇女（流产次数> 5）。对照组包括20个在怀孕前三个月的妇女和20个在卵泡期未怀孕的健康女性。
结果：我们观察到，URSA组中测得的抗氧化剂水平明显低于对照组（每次比较，p <0.05）。与对照相比，URSA组中检测到更高的TNF-α，MDA和NO产生（每次比较，p <0.05）。与URSA> 5相比，URSA 3-5与抗氧化剂水平高和TNF-α水平低有关。
结论：抗氧化剂的防御能力下降和氧化反应性物质的增加可能是造成流产的原因，因为它们的产生可能会造成损害。此外，TNF-α的水平显然与URSA的发病机理有关。