Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

We have sequenced and compared DNA from the ends of three human chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub- domains with entirely different patterns of homology to other chromosome ends. The distal regions contain numerous, short (<2 kb) segments of interrupted homology to many other human telomeric regions. The proximal regions show much longer (approximately 10-40 kb) uninterrupted homology to a few chromosome ends. A comparison of all yeast subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG repeats into distal and proximal sub-domains with similarly different patterns of identity to other non-homologous chromosome ends. Sequence comparisons indicate that the distal and proximal sub-domains do not interact with each other and that they interact quite differently with the corresponding regions on other, non- homologous, chromosomes. These findings suggest that the degenerate TTAGGG repeats identify a previously unrecognized, evolutionarily conserved boundary between remarkably different subtelomeric domains.      

Digital peer‐to‐peer information seeking and sharing: Opportunities for education and collaboration in newborn screening

Parents use the internet to connect with their peers and access information about a multitude of health topics, including newborn screening (NBS). As the NBS system evolves, education about NBS must be evaluated and updated to remain accessible and beneficial to parents. In this article, we aim to describe parents' current NBS educational needs and highlight areas to improve newborn screening education by detailing an analysis of NBS posts on an online parenting discussion platform. We analyzed a total of 317 discussion posts on BabyCenter®, finding that parents had questions about and desired support around many aspects of NBS including processes, results, and follow‐up. As a result of this analysis, three recommendations to improve NBS education were developed. Through collaboration and by leveraging technology, we can provide parents with accessible, timely, and desired NBS informational and social support.     

A 3 year retrospective review of intrauterine insemination, using cryopreserved donor spermatozoa and cycle monitoring by urinary or serum luteinizing hormone measurements

Insemination with donor spermatozoa is an integral part of infertility treatment. For the last 3 years in our unit, intrauterine insemination with donor spermatozoa (IUID) has been used in preference to vaginal insemination. In this retrospective study, patients were offered an initial course of five single intrauterine inseminations with cryopreserved donor spermatozoa and treatment was then reviewed. A total of 389 patients received 1465 inseminations. In all, 1119 cycles were monitored using luteinizing hormone serum analyses and 346 cycles using the urine home test kits. The clinical pregnancy rate per insemination for the cycles monitored by the serum assay was 18.0% (202/1119) compared with the urine cycles (13.7%, 46/346) (P <05). The pregnancy loss rate was not significantly different (14.4%, 29/202 and 21.7%, 10/46) (serum and urine cycles respectively). The viable clinical pregnancy rate was significantly higher (P <03) for the serum cycles than for the cycles using the urinary monitoring (15.5%, 173/1119 and 10.4%, 36/346 respectively). The cycles monitored by serum assay had a significantly higher cumulative viable clinical pregnancy rate (P <0001) of 70.2% after nine inseminations compared with the urine monitored cycles of 54.8%. The majority of patients opted for the serum cycles, with a minority self-selecting the urine cycles mainly for travelling convenience. The explanation for the significant differences between the viable clinical pregnancy rates per insemination and the cumulative viable clinical pregnancy rates may be due to the sensitivity of the urine home test kit or the patients' interpretation of the result.      

Comparison of the intensity and duration of effects of inhaled bitolterol and albuterol on airway caliber and airway responsiveness to histamine

Inhaled beta-agonists can produce bronchodilatation and reduce airway hyperreactivity in patients with asthma. Using these two measures, we compared inhaled bitolterol (three puffs, 1110 micrograms), albuterol (two puffs, 180 micrograms), and placebo administered by metered-dose inhaler in a blinded, crossover study of 40 subjects with chronic asthma. On each study day, subjects underwent histamine challenges at 1 1/2 hours before, and 1/2, 2, 4, 6, and 8 hours after inhaling one of the three test-drug treatments. Both drugs produced significant bronchodilatation at 30 minutes through 4 hours and significant effects on airway reactivity at 30 minutes through 2 hours (p less than 0.05). Bitolterol also produced small but significant bronchodilator effects at 6 hours and effects on airway reactivity at 4 hours (p less than 0.05). Effects of bitolterol on airway reactivity diminished significantly more slowly than effects of albuterol in subjects with baseline provocative concentration causing a 20% fall in FEV1 greater than or equal to 1.0 mg/ml of histamine (half-life of biologic effect 1.37 versus 0.92 hours; p less than 0.05) but not in subjects with baseline provocative concentration causing a 20% fall in FEV1 less than or equal to 1.0 mg/ml (half-life of biologic effect of 1.01 versus 1.00 hours; p greater than 0.05).     

肝细胞核因子6在小鼠肝内胆管发育过程中的表达

目的 探讨肝细胞核因子6(HNF6)在肝内胆管发育过程中的作用. 方法 用RT-PCR及免疫组织化学等方法 检测HNF6在小鼠胚胎发育的各个阶段以及成年肝中的表达. 结果 RT-PCR结果 显示,HNF6 mRNA的表达在E9d开始出现,与肝芽形成的时间吻合,E13d HNF6 mRNA的表达消失,E15d又重新出现,并一直维持到出生.免疫组织化学显示,CK19免疫反应在E13d开始出现,此时免疫反应阳性细胞在肝索内散在分布.E15d时在近肝门处的门管区丌始出现由单层的、CK19阳性细胞组成的胆管板,之后,阳性细胞反应主要分布于胆管板和小叶间胆管.E9～11d,多数肝索细胞呈HNF6阳性反应,E13d的肝索中未观察剑HNF6的表达.E15～17d,HNF6阳性反应的分布与CK19相似,成年小鼠肝的胆管上皮细胞仍呈HNF6阳性反应. 结论 HNF6可能与肝干细胞的特化关系不大,而与肝发育的启动、肝干细胞向胆管上皮细胞的分化及其分化状态的维持有关.     

细胞外信号调节激酶在TPPB促进PC12产生可溶性淀粉样前体蛋白中的作用

目的：观察在蛋白激酶C(PKC)激动剂TPPB促进可溶性淀粉样前体蛋白(sAPPα)释放过程中参与的信号转导通路。方法:以1 μmol/L的TPPB作用于PC12细胞3 h，同时加入信号转导通路的抑制剂，Western印迹法检测上清液内sAPPα的含量和细胞外信号调节激酶(p42/44MAPK)及磷酸化的p42/44MAPK的表达。结果:1 μmol/L的TPPB作用于PC12细胞3 h可以显著增加上清液内sAPPα的含量，细胞外信号调节激酶抑制剂U0126、c-Jun氨基末端激酶抑制剂SP600125和蛋白酪氨酸激酶抑制剂genistein可以部分消除此作用；而p38MAPK抑制剂SB203580对sAPPα的含量无显著影响。1 μmol/L的TPPB可以使磷酸化的p42/44MAPK表达增加，而对总的p42/44MAPK无显著影响。结论:细胞外信号调节激酶、c-Jun氨基末端激酶和蛋白酪氨酸激酶可能参与TPPB促进sAPPα生成的过程。     

不同栓塞范围的急性肺栓塞动物模型建立

目的：制备不同栓塞范围的急性肺栓塞动物模型,研究血流动力学变化与肺栓塞范围的相关性。方法:经导管注入犬自体血栓选择性栓塞肺动脉，通过控制注入血栓数量、速度，分别建立不同栓塞范围的急性肺栓塞动物模型；比较栓前、栓后15 min、30 min、1 h及2 h血流动力学指标变化，同时观察心脏超声影像学变化。结果:自体血栓均按要求阻塞相应肺动脉，肺栓塞形成后心输出量下降，肺动脉压力及肺毛细血管楔压显著增高，并在0.5 -1 h达到峰值，各血流动力学指标随肺栓塞范围增大而变化更显著。结论:此急性肺栓塞动物模型制作方法确切可行。