Characterization of the short neuropeptide F receptor from Drosophila melanogaster

A seven transmembrane G-protein coupled receptor has been cloned from Drosophila melanogaster. This receptor shows structural similarities to vertebrate Neuropeptide Y(2) receptors and is activated by endogenous Drosophila peptides, recently designated as short neuropeptide Fs (sNPFs). sNPFs have so far been found in neuroendocrine tissues of four other insect species and of the horseshoe crab. In locusts, they accelerate ovarian maturation, and in mosquitoes, they inhibit host-seeking behavior. Expression analysis by RT-PCR shows that the sNPF receptor (Drm-sNPF-R) is present in several tissues (brain, gut, Malpighian tubules and fat body) from Drosophila larvae as well as in ovaries of adult females. All 4 Drosophila sNPFs clearly elicited a calcium response in receptor expressing mammalian Chinese hamster ovary cells. The response is dose-dependent and appeared to be very specific. The short NPF receptor was not activated by any of the other tested arthropod peptides, not even by FMRFamide-related peptides (also ending in RFamide), indicating that the Arg residue at position 4 from the amidated C-terminus appears to be crucial for the response elicited by the sNPFs.     

多巴胺D1和D2受体拮抗剂对针刺镇痛的增强

在兔K~+透入测痛模型上,应用高选择性的D_1或D_2受体拮抗剂、观察其对针刺镇痛的影响。结果表明,iv.D_2受体拮抗剂氟哌啶醇和氯氮平加强针刺镇痛,且与剂量有关。icv.D_2受体拮抗剂domperidone和舒必利及D_1受体拮抗剂SCH23390,亦能加强针刺镇痛。本文对D_1和D_2受体拮抗剂在针刺镇痛中的作用进行了讨论。     

开窍醒神补虚通络针刺治疗对脑卒中后偏瘫患者血液流变学和Notch信号通路的影响

摘要 目的：探讨开窍醒神补虚通络针刺治疗对脑卒中后偏瘫患者血液流变学和Notch信号通路的影响。方法：选取东莞市中医院2020年12月至2022年7月期间收治的110例脑卒中后偏瘫患者,按照随机数字表法分为观察组（55例,脑卒中常规康复治疗结合开窍醒神补虚通络针刺治疗）和对照组（55例,脑卒中常规康复治疗）。对比两组各项量表评分[日常生活能力量表（ADL）、美国国立卫生研究院卒中量表（NIHSS）、Fugl-Meyer量表（FMA）]、平衡功能[前后倾斜角（F-BIA）、左右倾斜角（L-RIA）、Berg平衡量表（BBS）]、血液流变学和Notch信号通路相关指标。结果：与对照组相比,观察组干预4周后ADL、FMA评分更高,NIHSS评分更低（P<0.05）。与对照组相比,观察组干预4周后BBS、F-BIA、L-RIA更高（P<0.05）。与对照组相比,观察组干预4周后全血高切黏度、纤维蛋白原、血浆黏度、全血低切黏度更低（P<0.05）。与对照组相比,观察组干预4周后Notch1信使核糖核酸（mRNA）、Notch2 mRNA、Jagged1 mRNA、Jagged2 mRNA更低（P<0.05）。结论：开窍醒神补虚通络针刺治疗可有效改善脑卒中后偏瘫患者的日常活动能力、神经功能、运动功能和平衡功能,改善血液流变学和Notch信号通路。     

温针灸联合平衡针刀对椎动脉型颈椎病患者椎动脉血流、颈椎关节活动度及生活质量的影响

摘要 目的：探讨椎动脉型颈椎病（CSA）患者应用温针灸联合平衡针刀治疗对椎动脉血流、颈椎关节活动度及生活质量的影响。方法：选取首都医科大学附属北京中医医院于2020年1月-2023年1月收治的150例CSA患者,按治疗方案的不同进行分组,对照组（75例）行温针灸治疗,研究组（75例）行温针灸联合平衡针刀治疗,对比两组疗效、生活质量、颈椎关节活动度、颈椎功能、椎动脉血流指标。结果：研究组96.00%（72/75）治疗总有效率高于对照组81.33%（61/75）（P＜0.05）;研究组治疗后左椎动脉收缩期峰值血流速度、右椎动脉收缩期峰值血流速度高于对照组（P＜0.05）;研究组治疗后3周屈伸活动角度、旋转活动角度高于对照组（P＜0.05）;研究组治疗后1周、2周及3周NDI评分较对照组均更低（P＜0.05）;研究组治疗后健康调查简表（SF-36）各项评分高于对照组（P＜0.05）。结论：CSA应用温针灸联合平衡针刀治疗,可改善颈椎关节活动度,促进颈椎功能恢复,有利于椎动脉血流状况改善,并提高生活质量。     

Interpretation of metameric architecture in dominant shrubs of the Chilean matorral

Summary The seasonal progression of phenophases in 21 shrub species of the Chilean matorral was analyzed. Five modules or basic units that are responsible for the aboveground architecture of the plants were characterized. These modules appear to be organized in seven different spatial arrangements. In drought-deciduous species a module type with an absolute short shoot with limited apical growth, leafy or spiny, predominated. In evergreen species long shoot and temporal leafy short shoot module types were more frequent. The spatial arrangement of morphologically different modules and the temporal sequence of their formation allow a dynamic interpretation of the modular architecture of the plants.     

The MDMX Acidic Domain Uses Allovalency to Bind Both p53 and MDMX

Autoinhibition of p53 binding to MDMX requires two short-linear motifs (SLiMs) containing adjacent tryptophan (WW) and tryptophan-phenylalanine (WF) residues. NMR spectroscopy was used to show the WW and WF motifs directly compete for the p53 binding site on MDMX and circular dichroism spectroscopy was used to show the WW motif becomes helical when it is bound to the p53 binding domain (p53BD) of MDMX. Binding studies using isothermal titration calorimetry showed the WW motif is a stronger inhibitor of p53 binding than the WF motif when they are both tethered to p53BD by the natural disordered linker. We also investigated how the WW and WF motifs interact with the DNA binding domain (DBD) of p53. Both motifs bind independently to similar sites on DBD that overlap the DNA binding site. Taken together our work defines a model for complex formation between MDMX and p53 where a pair of disordered SLiMs bind overlapping sites on both proteins.     

Forces-induced pinpoint denaturation of short DNA

A method that can pinpoint control DNA denaturation is reported. In the single molecule experiment using spFRET, DNA adhered on a quartz surface is acted upon by both a weak laser field force and a fast temporal mechanical force. The experiment showed that increasing strengths of laser power result in increasing percentage of denatured DNA; different mechanical forces produce different numbers of DNA opening. Besides the method’s simplicity and convenience for DNA melting, its crucial advantage and potential application is the ability to denature DNA at specified locations, i.e., a weak laser and a fast temporal mechanical force can be used in pinpoint denaturation of short DNA.     

Proteasome modulating agents induce rAAV2-mediated transgene expression in human intestinal epithelial cells

Intestinal gene transfer offers promise as a therapeutic option for treatment of both intestinal and non-intestinal diseases. Recombinant adeno-associated virus serotype 2, rAAV2, based vectors have been utilized to transduce lung epithelial cells in culture and in human subjects. rAAV2 transduction of intestinal epithelial cells, however, is limited both in culture and in vivo. Proteasome-inhibiting agents have recently been shown to enhance rAAV2-mediated transgene expression in airway epithelial cells. We hypothesized that similar inhibition of proteasome-related cellular processes can function to induce rAAV2 transduction of intestinal epithelial cells. Our results demonstrate that combined treatment with proteasome-modulating agents MG101 (N-acetyl-L-leucyl-L-leucyl-L-norleucine) and Doxorubicin synergistically induces rAAV2-mediated luciferase transgene expression by >400-fold in undifferentiated Caco-2 cells. In differentiated Caco-2 monolayers, treatment with MG101 and Doxorubicin induces transduction preferentially from the basolateral cell surface. In addition to Caco-2 cells, treatment with MG101 and Doxorubicin also results in enhanced rAAV2 transduction of HT-29, T84, and HCT-116 human intestinal epithelial cell lines. We conclude that MG101 and Doxorubicin mediate generic effects on intestinal epithelial cells that result in enhanced rAAV2 transduction. Use of proteasome-modulating agents to enhance viral transduction may facilitate the development of more efficient intestinal gene transfer protocols.     

A novel method for the intracellular delivery of siRNA using microbubble-enhanced focused ultrasound

Short interfering RNA (siRNA) has attracted much attention for clinical use in various diseases. However, its delivery, especially through the cell membrane, continues to present a challenge. Advances in ultrasound- and ultrasound contrast-agent technologies have made it possible to change transiently the permeability of the cell membrane and, using a focused ultrasound transducer, to narrow and focus the ultrasound energy on a small target, thereby avoiding damage to surrounding tissue. In this in vitro study, we demonstrate that it is possible to deliver siRNA intracellularly via microbubble-enhanced focused ultrasound. Although further optimization is necessary, our novel method for siRNA transduction represents a powerful tool for using siRNA in vivo and possibly in the clinical setting.