Conserved Non-Coding Regulatory Signatures in Arabidopsis Co-Expressed Gene Modules

Complex traits and other polygenic processes require coordinated gene expression. Co-expression networks model mRNA co-expression: the product of gene regulatory networks. To identify regulatory mechanisms underlying coordinated gene expression in a tissue-enriched context, ten Arabidopsis thaliana co-expression networks were constructed after manually sorting 4,566 RNA profiling datasets into aerial, flower, leaf, root, rosette, seedling, seed, shoot, whole plant, and global (all samples combined) groups. Collectively, the ten networks contained 30% of the measurable genes of Arabidopsis and were circumscribed into 5,491 modules. Modules were scrutinized for cis regulatory mechanisms putatively encoded in conserved non-coding sequences (CNSs) previously identified as remnants of a whole genome duplication event. We determined the non-random association of 1,361 unique CNSs to 1,904 co-expression network gene modules. Furthermore, the CNS elements were placed in the context of known gene regulatory networks (GRNs) by connecting 250 CNS motifs with known GRN cis elements. Our results provide support for a regulatory role of some CNS elements and suggest the functional consequences of CNS activation of co-expression in specific gene sets dispersed throughout the genome.     

铼-188标记生物分子在肿瘤治疗中的应用

目的：研究铼．188标记生物分子在肿瘤治疗中的应用。方法：选取小白鼠作为实验的研究对象,将荷瘤鼠的肉瘤切成小块接种到小白鼠身上,达到试验条件时使用,即将没有明显差异的小白鼠16只随机分为4组,每组4只,注射含有铼一188的药物后分别在不同的时间将其处死,之后取出重要器官进行测量分析,进而得出铼一188的应用效果。结果：瘤内注射的要去在不同时间放射性在瘤内的保持率分别为（90．5±7．7）D％（1h）,（92．2±8．6）D％（24h）,（88．3±10．9）D％（48h）和（91．5±7．6）D％（72h）,在荷瘤鼠内注入生理盐水、非放硫化铼和188Re．硫化铼混悬液,肿瘤质量分别为2885．3±1241.3、2839．9±1965．2和98．4±45．5mg。188Re-硫化铼混悬液在生理盐水、磷酸盐缓冲液和小牛血清中均可稳定72h,而且188W-188Re发生器的应用还可以降低188Re-硫化铼混悬液的价格。随着处死时间的延迟,小鼠肿瘤质量和体积逐渐减小,相临两组比较,后组测定值均明显小于前组,数据经统计学比较具有显著差异（P〈0．05）。结论：188Re-硫化铼混悬液是一种适宜的肿瘤治疗剂。     

First case of highly pathogenic H5N1 avian influenza virus in Spain

Background  

In August 2006 a major epidemic of bluetongue virus serotype 8 (BTV8) started off in North-West Europe. In the course of 2007 it became evident that BTV8 had survived the winter in North-West Europe, re-emerged and spread exponentially. Recently, the European Union decided to start vaccination against BTV8. In order to improve the understanding of the epidemiological situation, it was necessary to execute a cross-sectional serological study at the end of the BT vector season. Cattle were the target species for cross-sectional serological studies in Europe at the end of 2006 and 2007. However, there was no information on the BTV8-seroprevalence in sheep and goats.     

Efficient copackaging and cotransport yields postsynaptic colocalization of neuromodulators associated with synaptic plasticity

Recent data suggest that tissue plasminogen activator (tPA) influences long-term plasticity at hippocampal synapses by converting plasminogen into plasmin, which then generates mature brain-derived neurotrophic factor (mBDNF) from its precursor, proBDNF. Motivated by this hypothesis, we used fluorescent chimeras, expressed in hippocampal neurons, to elucidate (1) mechanisms underlying plasminogen secretion from hippocampal neurons, (2) if tPA, plasminogen, and proBDNF are copackaged and cotransported in hippocampal neurons, especially within dendritic spines, and (3) mechanisms mediating the transport of these neuromodulators to sites of release. We find that plasminogen chimeras traffic through the regulated secretory pathway of hippocampal neurons in dense-core granules (DCGs) and that tPA, plasminogen, and proBDNF chimeras are extensively copackaged in DCGs throughout hippocampal neurons. We also find that 80% of spines that contain DCGs contain chimeras of these neuromodulators in the same DCG. Finally, we demonstrate, for the first time, that neuromodulators undergo cotransport along dendrites in rapidly mobile DCGs, indicating that neuromodulators can be efficiently recruited into active spines. These results support the hypothesis that tPA mediates synaptic activation of BDNF by demonstrating that tPA, plasminogen, and proBDNF colocalize in DCGs in spines, where these neuromodulators can undergo activity-dependent release and then interact and/or mediate changes that influence synaptic efficacy. The results also raise the possibility that frequency-dependent changes in extents of neuromodulator release from DCGs influence the direction of plasticity at hippocampal synapses by altering the relative proportions of two proteins, mBDNF and proBDNF, that exert opposing effects on synaptic efficacy.     

A fluorimetric assay for real-time monitoring of adenylyl cyclase activity based on terbium norfloxacin

Adenylyl cyclases catalyze the production of the second messenger cyclic AMP from ATP. Until now, there has been no fluorescent adenylyl cyclase assay known that is applicable to high-throughput screening and kinetic determinations that can directly monitor the turnover of the unmodified substrate ATP. In this study, a fluorescence-based assay is described using the Ca(II)- and calmodulin-dependent adenylyl cyclase edema factor (EF) from Bacillus anthracis and Tb(III)-norfloxacin as probe for the enzyme activity. This assay can be used to study enzyme regulators, allows real-time monitoring of adenylyl cyclase activity, and does not substitute ATP by fluorescent derivatives. These derivatives must be judged critically due to their interference on the activity of enzymes. Furthermore, the new assay makes redundant the application of radioactively labeled substrates such as [α-³²P]ATP or fluorescently labeled antibodies such as anti-cyclic AMP. We determined the Michaelis-Menten constant (K_M), the v₀^max value of ATP turnover, and the IC₅₀ values for three inhibitors of EF by this newly developed fluorescent method.     

Use of Biochronology to Examine Interactions of Freshwater Drum, Walleye and Yellow Perch in the Red Lakes of Minnesota

Growth histories for freshwater drum, Aplodinotus grunniens, walleye, Stizostedion vitreum, and yellow perch, Perca flavescens, were constructed using calcified structures for the period 1947 through 1996 for the Red Lakes, Minnesota. Increased walleye growth and decreased yellow perch growth were observed over the period from 1983 to 1996, which are attributed to intensive fishing resulting in decreased intraspecific competition in walleye and increased intraspecific competition in yellow perch through release from predation. Strong year-classes of yellow perch were positively correlated with walleye growth (r=0.57, p-value=0.042). There was no evidence for interactions of walleye or yellow perch with freshwater drum. Freshwater drum growth (r=0.680, p-value=0.0001) was more highly correlated with temperature than were walleye (r=0.386, p-value=0.006) and yellow perch growth (r=0.303, p-value=0.036).     

Studies towards the next generation of antidepressants. Part 1: Indolylcyclohexylamines as potent serotonin reuptake inhibitors.

A series of indolylcyclohexylamines possessing potent and selective serotonin reuptake inhibition is reported. The most interesting compounds proved to have subnanomolar 5-HT transporter activity, and exhibited moderate 5-HT(1A) affinity.     

Portal vein insulin response of glucose intolerant Yucatan miniature swine to common secretogogues

A group of glucose intolerant miniature swine exhibiting an impaired portal vein insulin response to an IVGTT were examined with respect to their portal vein insulin response to the secretogogues: isoproterenol, arginine and leucine. Equivalent insulin responses to isoproterenol and leucine were noted on the part of the glucose intolerant animals when compared to control subjects. An impaired portal vein insulin response was evident during an infusion of 0.5 g/kg arginine and again when a pulse injection of .25 g/kg glucose was administered in the presence of isoproterenol (.05 microgram/kg . min). The close agreement of these results with those reported for human diabetics suggests that a similar pancreatic defect, most probably associated with the glucoreceptor, is present in this group of glucose intolerant miniature swine.     

45Ca and (14C)EDTA efflux from dialyzed barnacle muscle fibers.

45Ca and 14C-labeled ethylenediamine-N, N'-tetraacetic acid (EDTA) effluxes were measured in internally dialyzed barnacle muscle fibers. In 45Ca experiments the internal ionized 45Ca was fixed at 0.2 muM with ethyleneglycolbis-(beta-aminoethylether)-N, N'-tetraacetic acid(EGTA). The 45Ca efflux was found to increase with internal CaEGTA from 0.05 pmol/cm2.s(CaEGTA equal to 0.02 mM) to 5.0 pmol/cm2.s(CaEGTAequal to 9.6 mM). To determine whether or not most of this increase in efflux was due to the exit of undissociated CaEGTA, comparable experiments were performed with Ca-[14-C]EDTA. Over the same range of internal calcium as studied in the 45Ca experiments, the Ca-[14-C]EDTA efflux was no more than 12% of the 45Ca efflux. We conclude that the exit of undissociated 45Ca cannot account for most of the 45Ca efflux nor can it account for the dependence of 45Ca efflux on internal CaEGTA. The experiments also demonstrated the existence of an endogenous pool of calcium, of 0.43 mmol/kg (about half the total calcium), which remained unexchanged during dialysis.