Detection of sequences in the cerebellar cortex: numerical estimate of the possible number of tidal-wave inducing sequences represented

The two major cortices of the brain--the cerebral and cerebellar cortex--are massively connected through intercalated nuclei (pontine, cerebellar and thalamic nuclei). We suggest that the two cortices co-operate by generating precise temporal patterns in the cerebral cortex that are detected in the cerebellar cortex as temporal patterns assembled spatially in the mossy fibers. We will begin by showing that the tidal-wave mechanism works in the cerebellar cortex as a read-out mechanism for such spatio-temporal patterns due to the synchronous activity they generate in the parallel fiber system which drives the Purkinje cells--the output neurons of the cerebellar cortex--to fire action potentials. We will review the anatomy of the mossy fibers and show that within a "beam", or "row" of cerebellar cortex the mossy fibers in principle could embed a vast number of tidal-wave generating sequences. Based on anatomical data we will argue that the cerebellar mossy fiber-granule cell-Purkinje cell system can potentially detect and--through learning--select from an enormous number of spatio-temporal patterns.     

Patterns of Allelic Diversity in Spring Wheat Populations by SSR-Markers

Precise assessment of diversity in available breeding germplasm helps to preempt epidemics and abrupt environmental changes. Spring wheat germplasm consisting of 84 accessions including cultivars, breeding lines and landraces from various origins was scanned with 44 SSRs. For allele frequencies, allelic patterns, heterozygosity and polymorphism the selected population was divided in three subpopulations: (i) pre-green revolution (pre-1965), (ii) post-green revolution (post-1965), (iii) post-veery (post-2000). Alleles produced in pre-1965, post-1965 and post-2000 subpopulations were 115, 144 and 131, respectively. Mean PIC values for pre-1965, post-1965 and post-2000 subpopulations were 0.48, 0.52 and 051, respectively. Allelic patterns showed no locally common alleles in any of the subpopulation. The pre-1965 subpopulation had also no private allele, however, average number of private alleles decreased from post-1965 to post-2000 subpopulation. In case of effective alleles and Shannon’s information index trend was increasing from pre-1965 to post-1965 and then decreasing from post-1965 to post-2000. The decreasing trend alarms the reduced genetic diversity in wheat varieties developed after 2000. PCA and cluster analysis didn’t clearly differentiated subpopulations, though pre-1965 genotypes showed higher genetic distance from post-1965 and post-2000 subpopulations. The decreasing measures of genetic diversity in post-2000 wheat genotypes should be a concern for wheat breeders, therefore, all sources of broadening genetic diversity should be exploited.     

短毛柽柳不同部位中总黄酮含量及稳定性研究

目的：比较短毛柽柳中不同部位总黄酮的含量差异,研究黄酮化合物保存的条件,方法：采用超声波乙醇浸提法,在正交优先的最佳条件（料液比为1∶15,超声处理时间为40min,乙醇浓度为45%,超声温度50℃,提取3次）下提取不同部位总黄酮,并测定不同条件下其吸光度的变化。结果：柽柳花、叶、茎中总黄酮得率分别为24.585mg/g、25.623mg/g、41.726mg/g,柽柳中提取的黄酮溶液在光照、高温、高浓度蔗糖溶液和Na＋存在条件下不稳定;pH 4~7条件下较稳定;氧化剂对其稳定性的影响不大。结论：柽柳茎中总黄酮含量明显高于其他两个部位。柽柳黄酮保存时应避免接触碳水化合物和盐离子,在避光、常温、中性条件下保存。     

Diagnostic Value of a Rec-ELISA Using Toxoplasma gondii Recombinant SporoSAG,BAG1, and GRA1 Proteins in Murine Models Infected Orally with Tissue Cysts and Oocysts

Toxoplasma gondii causes congenital toxoplasmosis in newborns resulting with fetal anomalies. Determining the initiation time of infection is very important for pregnant women and current serological assays have drawbacks in distinguishing the recently acute toxoplasmosis. Diagnosis of recently acute infection may be improved by using stage specific antigens in serological assays. In the present study, the diagnostic value of sporozoite specific SporoSAG, bradyzoite specific BAG1 proteins and GRA1 protein expressed by all forms of the parasite have been evaluated ELISA using sera systematically collected from mice administered orally with tissue cyst and oocysts. The anti-SporoSAG IgM antibodies in sera obtained from mice infected with oocysts peaked significantly at days 1, 10, and 15 (P<0.01). The anti-BAG1 IgM antibodies in sera obtained from mice infected with tissue cysts peaked significantly at days 15, 40, and 120 (P<0.05). The anti-GRA1 IgM antibodies in sera obtained from mice infected with oocysts peaked significantly at days 2, 10, and 40 (P<0.01). The anti-GRA1 IgM antibodies in sera obtained from mice infected with tissue cysts peaked significantly only at day 40 (P<0.05). The anti-SporoSAG, anti-BAG1, and anti-GRA1 IgG titers of mice showed significant increases at day 40 (P<0.05) and decrement started for only anti-GRA1 IgG at day 120. The presence of anti-SporoSAG IgM and IgG antibodies can be interpreted as recently acute infection between days 10–40 because IgM decreases at day 40. Similarly, presence of anti-BAG1 IgM and absence of IgG can be evaluated as a recently acute infection that occurred 40 days before because IgG peaks at day 40. A peak in anti-GRA1 antibody level at first testing and reduction in consecutive sample can be considered as an infection approximately around day 40 or prior. Overall, recombinant SporoSAG, BAG1 and GRA1 proteins can be accepted as valuable diagnostic markers of recently acute toxoplasmosis.     

Discovery of new 3-methylquinoxalines as potential anti-cancer agents and apoptosis inducers targeting VEGFR-2: design,synthesis, and in silico studies

There is an urgent need to design new anticancer agents that can prevent cancer cell proliferation even with minimal side effects. Accordingly, two new series of 3-methylquinoxalin-2(1H)-one and 3-methylquinoxaline-2-thiol derivatives were designed to act as VEGFR-2 inhibitors. The designed derivatives were synthesised and evaluated in vitro as cytotoxic agents against two human cancer cell lines namely, HepG-2 and MCF-7. Also, the synthesised derivatives were assessed for their VEGFR-2inhibitory effect. The most promising member 11e were further investigated to reach a valuable insight about its apoptotic effect through cell cycle and apoptosis analyses. Moreover, deep investigations were carried out for compound 11e using western-plot analyses to detect its effect against some apoptotic and apoptotic parameters including caspase-9, caspase-3, BAX, and Bcl-2. Many in silico investigations including docking, ADMET, toxicity studies were performed to predict binding affinity, pharmacokinetic, drug likeness, and toxicity of the synthesised compounds. The results revealed that compounds 11e, 11g, 12e, 12g, and 12k exhibited promising cytotoxic activities (IC₅₀ range is 2.1 − 9.8 µM), comparing to sorafenib (IC₅₀ = 3.4 and 2.2 µM against MCF-7 and HepG2, respectively). Moreover, 11b, 11f, 11g, 12e, 12f, 12g, and 12k showed the highest VEGFR-2 inhibitory activities (IC₅₀ range is 2.9 − 5.4 µM), comparing to sorafenib (IC₅₀ = 3.07 nM). Additionally, compound 11e had good potential to arrest the HepG2 cell growth at G2/M phase and to induce apoptosis by 49.14% compared to the control cells (9.71%). As well, such compound showed a significant increase in the level of caspase-3 (2.34-fold), caspase-9 (2.34-fold), and BAX (3.14-fold), and a significant decrease in Bcl-2 level (3.13-fold). For in silico studies, the synthesised compounds showed binding mode similar to that of the reference compound (sorafenib).     

Microbial transformation of 17alpha-ethynyl- and 17alpha-ethylsteroids, and tyrosinase inhibitory activity of transformed products

The microbial transformation of the 17alpha-ethynyl-17beta-hydroxyandrost-4-en-3-one (1) (ethisterone) and 17alpha-ethyl-17beta-hydroxyandrost-4-en-3-one (2) by the fungi Cephalosporium aphidicola and Cunninghamella elegans were investigated. Incubation of compound 1 with C. aphidicola afforded oxidized derivative, 17alpha-ethynyl-17beta-hydroxyandrosta-1,4-dien-3-one (3), while with C. elegans afforded a new hydroxy derivative, 17alpha-ethynyl-11alpha,17beta-dihydroxyandrost-4-en-3-one (4). On the other hand, the incubation of compound 2 with the fungus C. aphidicola afforded 17alpha-ethyl-17beta-hydroxyandrosta-1,4-dien-3-one (5). Two new hydroxylated derivatives, 17alpha-ethyl-11alpha,17beta-dihydroxyandrost-4-en-3-one (6) and 17alpha-ethyl-6alpha,17beta-dihydroxy-5alpha-androstan-3-one (7) were obtained from the incubation of compound 2 with C. elegans. Compounds 1-6 exhibited tyrosinase inhibitory activity, with compound 6 being the most potent member (IC(50)=1.72 microM).     

Protease‐activated receptor‐1 modulates hippocampal memory formation and synaptic plasticity

Protease‐activated receptor‐1 (PAR1) is an unusual G‐protein coupled receptor (GPCR) that is activated through proteolytic cleavage by extracellular serine proteases. Although previous work has shown that inhibiting PAR1 activation is neuroprotective in models of ischemia, traumatic injury, and neurotoxicity, surprisingly little is known about PAR1's contribution to normal brain function. Here, we used PAR1?/? mice to investigate the contribution of PAR1 function to memory formation and synaptic function. We demonstrate that PAR1?/? mice have deficits in hippocampus‐dependent memory. We also show that while PAR1?/? mice have normal baseline synaptic transmission at Schaffer collateral‐CA1 synapses, they exhibit severe deficits in N‐methyl‐d ‐aspartate receptor (NMDAR)‐dependent long‐term potentiation (LTP). Mounting evidence indicates that activation of PAR1 leads to potentiation of NMDAR‐mediated responses in CA1 pyramidal cells. Taken together, this evidence and our data suggest an important role for PAR1 function in NMDAR‐dependent processes subserving memory formation and synaptic plasticity.     

肉苁蓉总黄酮含量的测定

目的：从肉苁蓉中提取并测定总黄酮含量,选择最佳提取工艺条件。方法：以芦丁为对照品,用分光光度法在最大吸收波长510nm对其含量进行测定。结果：测得样品中总黄酮含量C=9．33％,最佳提取工艺：乙醇浓度为70％、料液比1：40、回流时间2h、回流温度70℃。结论：选用芦丁为对照品应用于紫外分光光度法测定肉苁蓉总黄酮含量准确度较高,方法简单,是切实可行含量测定方法。     

Cytotoxic and genotoxic effects of <Emphasis Type="Italic">Lavandula stoechas</Emphasis> aqueous extracts

Lavandula genus is an important member of Labiatae (Lamiaceae) family. People use commonly Lavandula stoechas as a medicinal plant for various diseases around the world and also in Turkey. The aim of this study was to investigate cytotoxic and genotoxic effects of aqueous extracts (40, 80 and 120 g/L) from L. stoechas flowers on Allium cepa root tip meristem cells. For this purpose, A. cepa onion bulbs were treated with the above-mentioned L. stoechas flower extracts for 72 h. Spring water (pH 7.3) was used as a control. The result of this study sowed that aqueous extracts reduced mitotic index, but induced chromosome aberrations and mitotic aberrations in comparison with control, significantly (p < 0.05). Aqueous extracts induced breaks, stickiness, pole deviations and micronuclei. Furthermore, these effects were related to extract concentrations. These results showed that L. stoechas aqueous extracts have cytotoxic and genotoxic effects.