Taurine replacement attenuates hyperalgesia and abnormal calcium signaling in sensory neurons of STZ-D rats

The etiology of painful diabetic neuropathy is poorly understood, but may result from neuronal hyperexcitability secondary to alterations of Ca2+ signaling in sensory neurons. The naturally occurring amino acid taurine functions as an osmolyte, antioxidant, Ca2+ modulator, inhibitory neurotransmitter, and analgesic such that its depletion in diabetes may predispose one to neuronal hyperexcitability and pain. This study reports the effects of taurine replacement on hyperalgesia and sensory neuron Ca2+ homeostasis in streptozotocin-diabetic (STZ-D) rats. Nondiabetic and STZ-D rats were treated with a 2% taurine-supplemented diet for 6-12 wk. Thermal hyperalgesia and mechanical allodynia were determined by measuring hindpaw withdrawal latency to radiant heat and the withdrawal threshold to the von Frey anesthesiometer. Intracellular Ca2+ signaling was explored in neurons from L4-L6 dorsal root ganglia (DRG), using fura 2 fluorescence. Taurine replacement of diabetic rats attenuated deficits of nerve conduction and prevented reductions of mechanical and thermal withdrawal threshold and latency, respectively. In small DRG sensory neurons from diabetic rats, recovery of intracellular Ca2+ concentration ([Ca2+]i) in response to KCl was slowed and 73% corrected by taurine. The amplitudes of caffeine and ATP-induced [Ca2+]i transients were decreased by 47 and 27% (P < 0.05), respectively, in diabetic rat DRG sensory neurons and corrected by 74 and 93% (P < 0.05), respectively, by taurine replacement. These data indicate that taurine is important in the regulation of neuronal Ca2+ signaling and that taurine deficiency may predispose one to nerve hyperexcitability and pain, complicating diabetes.     

老年人认知训练的神经机制研究

伴随老化,老年人的认知和脑功能会表现出一定的下降趋势.尽管如此,人类的大脑到老年期都会保有一定的可塑性,认知训练的方式是延缓认知和脑功能衰退的有效手段.本文回顾了以往针对老年人不同类型的认知训练研究,探讨了认知训练的理论基础(包括放大观和补偿观),深入分析了老年人认知训练的神经机制,并在此基础上指出以往研究中理论基础冲突的不足和对未来研究老年人训练任务适配性的展望.     

Fertile plants regenerated from suspension culture-derived protoplasts of an indica type rice (Oryza sativa L.)

Calluses were induced from immature embryos of an indica type rice and finely dispersed cell suspension cultures were initiated from the callus using modified AA medium (S₁ medium). The suspension cultures were maintained alternatively (1–2 passages in each medium) in S₁ medium and S₂ medium, the latter containing KNO₃, NH₄NO₃, proline and glutamine as nitrogen source. Protoplasts of high quality were isolated form suspension cells cultured in S₂ medium supplemented with ABA. Embedding the protoplasts in agarose blocks containing NH₄NO₃-free modified KM8P(PM₁) medium and immersing the blocks in NH₄NO₃-containing modified KM8P(PM₃) medium were most effective for obtaining protoplast division and callus formation. The protoplast-derived calluses were precultured in potato extract-aand/or ABA-containing N₆(D₁, D₂ or D₃) media and many embryo-like structures were formed. These structures developed into plantlets after being transferred to N₆ differentiation (D₄) medium. The regenerated plantlets grew into mature plants and beard seeds normally.Abbreviations AA medium amino acids based medium - ABA abscisic acid - BA benzyladenine - 2,4-D 2,4-dichlorophenoxyacetic acid - DF division frequency - IAA indoleacetic acid - KIN kinetin - NAA naphthaleneacetic acid - PE planting efficiency     

糙叶败酱挥发油镇静作用的研究

本文观察了败酱科植物糙叶败酱(Patrinia scabra Bunge)根和根茎中制得的挥发油的镇静作用,井与黄花败酱挥发油做了比较。结果表明,此油灌胃给予数组小鼠,剂量0.45ml/kg,显示如下的作用:[1]能显著延长由于腹腔注射戊巴比妥钠(50mg/kg)引起的小鼠睡眠时间,但其作用强度弱于黄花败酱挥发油。(2)一次灌胃给予小鼠大剂量10.46g/kg的糙叶败酱挥发油,连续观察10天,动物外观正常,无一死亡,体重增加与对照组相似。     

Direct measurements of the kinematics and dynamics of bat flight

Experimental measurements and analysis of the flight of bats are presented, including kinematic analysis of high-speed stereo videography of straight and turning flight, and measurements of the wake velocity field behind the bat. The kinematic data reveal that, at relatively slow flight speeds, wing motion is quite complex, including a sharp retraction of the wing during the upstroke and a broad sweep of the partially extended wing during the downstroke. The data also indicate that the flight speed and elevation are not constant, but oscillate in synchrony with both the horizontal and vertical movements of the wing. PIV measurements in the transverse (Trefftz) plane of the wake indicate a complex 'wake vortex' structure dominated by a strong wing tip vortex shed from the wing tip during the downstroke and either the wing tip or a more proximal joint during the upstroke. Data synthesis of several discrete realizations suggests a 'cartoon' of the wake structure during the entire wing beat cycle. Considerable work remains to be done to confirm and amplify these results.     

Embryological Studies on Narcissus tazetta var. chinensis

Chinese narcissus (Narcissus tazetta var.chinensis Roem) blooms but has no seeds.Embryological studies on the species were conducted to discover the causes of its sterility.Its anther wall is composed of four layers of cells,and its tapetum is of the secretory type.The cytokinesis of microspore mother cells is of the successive type,and the tetrad is tetrahedral.During meiosis of microspore mother cells,some chromosomes lagged,and several micronuclei were found in tetrads.Only 27.7% of the pollen grains contained full cytoplasm,and 1.3% of them germinated in culture medium.No pollen grain,however,could germinate on the stigma.The ovary is trilocular with axile placenta,and the ovules are bitegmic,tenuinucellate,and anatropous.Its embryo sac is of the polygonum type.Most embryo sacs degenerated,and only about 4.5% of the ovules contained a normal embryo sac with an egg cell,two synergids,three antipodal,and a central cell containing two polar nuclei.One reason for the sterility of Chinese narcissus is the abnormality of microsporogenesis and megasporogenesis,in which only a few functional pollen grains and embryo sacs are produced.The other reason is that the pollen grains cannot germinate on the stigma.     

Proteinase-activated Receptor 2 Promotes Cancer Cell Migration through RNA Methylation-mediated Repression of miR-125b

Proteinase activated-receptor 2 (PAR₂) participates in cancer metastasis promoted by serine proteinases. The current study aimed to test the molecular mechanism by which PAR₂ promotes cancer cell migration. In different cancer cells, activation of PAR₂ by activating peptide (PAR₂-AP) dramatically increased cell migration, whereas knock down of PAR₂ inhibited cellular motility. The PAR₂ activation also repressed miR-125b expression while miR-125b mimic successfully blocked PAR₂-induced cell migration. Moreover, Grb associated-binding protein 2 (Gab2) was identified as a novel target gene of miR-125b and it mediated PAR₂-induced cell migration. The correlation of PAR₂ with miR-125b and Gab2 was further supported by the findings obtained from human colorectal carcinoma specimens. Remarkably, knock down of NOP2/Sun domain family, member 2 (NSun2), a RNA methyltransferase, blocked the reduction in miR-125b induced by PAR₂. Furthermore, PAR₂ activation increased the level of N⁶-methyladenosine (m⁶A)-containing pre-miR-125b in NSun2-dependent manner. Taken together, our results demonstrated that miR-125b mediates PAR₂-induced cancer cell migration by targeting Gab2 and that NSun2-dependent RNA methylation contributes to the down-regulation of miR-125b by PAR₂ signaling. These findings suggest a novel epigenetic mechanism by which microenvironment regulates cancer cell migration by altering miRNA expression.     

Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks

Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules). We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression.     

Thermal Stabilization of Dihydrofolate Reductase Using Monte Carlo Unfolding Simulations and Its Functional Consequences

Design of proteins with desired thermal properties is important for scientific and biotechnological applications. Here we developed a theoretical approach to predict the effect of mutations on protein stability from non-equilibrium unfolding simulations. We establish a relative measure based on apparent simulated melting temperatures that is independent of simulation length and, under certain assumptions, proportional to equilibrium stability, and we justify this theoretical development with extensive simulations and experimental data. Using our new method based on all-atom Monte-Carlo unfolding simulations, we carried out a saturating mutagenesis of Dihydrofolate Reductase (DHFR), a key target of antibiotics and chemotherapeutic drugs. The method predicted more than 500 stabilizing mutations, several of which were selected for detailed computational and experimental analysis. We find a highly significant correlation of r = 0.65–0.68 between predicted and experimentally determined melting temperatures and unfolding denaturant concentrations for WT DHFR and 42 mutants. The correlation between energy of the native state and experimental denaturation temperature was much weaker, indicating the important role of entropy in protein stability. The most stabilizing point mutation was D27F, which is located in the active site of the protein, rendering it inactive. However for the rest of mutations outside of the active site we observed a weak yet statistically significant positive correlation between thermal stability and catalytic activity indicating the lack of a stability-activity tradeoff for DHFR. By combining stabilizing mutations predicted by our method, we created a highly stable catalytically active E. coli DHFR mutant with measured denaturation temperature 7.2°C higher than WT. Prediction results for DHFR and several other proteins indicate that computational approaches based on unfolding simulations are useful as a general technique to discover stabilizing mutations.