Regulation of [3H]D-Aspartate Release by the 5-F2t-Isoprostane and Its 5-Epimer in Isolated Bovine Retina

We have evidence that 15-F?-isoprostanes (15-F?-IsoPs) regulate excitatory neurotransmitter release in ocular tissues. Although 5-F?-IsoPs are abundantly produced in mammals, their pharmacological actions on neurotransmitter release remain unknown. In the present study, we compared the effect of the 5-F?-IsoP epimer pair, 5-F(2t)-IsoP (C5-OH in β-position) and 5-epi-5-F(2t)-IsoP (C5-OH in α-position), on K?-evoked [3H]D-aspartate release in isolated bovine retina. We further examined the role of prostanoid receptors on the inhibitory action of 5-epi-5-F(2t)-IsoP on [3H]D-aspartate overflow. Isolated bovine retina were prepared for studies of K?-evoked release of [3H]D-aspartate using the superfusion method. 5-epi-5-F(2t)-IsoP (0.01 nM to 1 μM), attenuated K?-evoked [3H]D-aspartate release in a concentration-dependent manner, with the inhibitory effect of 26.9% (P < 0.001; IC?? = 0.2 μM) being achieved at 1 μM concentration. Its 5-(S)-OH-epimer, 5-F(2t)-IsoP (0.1 nM-1 μM), exhibited an inhibitory biphasic action, yielding a maximal response of 35.7% (P < 0.001) at 10 nM concentration of the drug (IC?? value of 3 nM). Although the prostanoid-receptor antagonists, AH 6809 (10 μM; EP???/DP) and BAY-u3405 (10 μM; DP/Tx) exhibited no effect on 5-epi-5-F(2t)-IsoP (10 nM-1 μM)-mediated inhibition, SC-19220 (1 μM; EP?) completely reversed 5-epi-5-F(2t)-IsoP (0.1 μM and 1 μM)-induced attenuation of K?-evoked [3H]D-aspartate release. Similarly, both SC-51322 (10 μM; EP? and AH 23848 (1 μM; EP?) reversed the inhibitory action elicited by 5-epi-5-F(2t)-IsoP (0.1 μM) on the neurotransmitter release. We conclude that the 5-F?-IsoP epimer pair, 5-F(2t)-IsoP and 5-epi-5-F(2t)-IsoP, attenuate K?-induced [3H]D-aspartate release in isolated bovine retina presumably via prostanoid receptor dependent mechanisms. The trans-orientation of the allylic hydroxyl group at position C5 accounts for the apparent biphasic response exhibited by 5-F(2t)-IsoP on excitatory neurotransmitter release.     

Incidence of dsRNA Mycoviruses in a Collection of Aspergillus fumigatus Isolates

A collection of clinical and environmental isolates of the opportunistic human pathogen, Aspergillus fumigatus, were screened for the presence of mycoviruses and 6.6?% of 366 isolates contained dsRNA segments ranging in size from ~1.0 to 4.0?kbp. The dsRNAs were categorised into three different groups comprising bipartite dsRNAs, quadripartite dsRNAs, representative isolates of which have both been sequenced, and an uncharacterised mycovirus, whose genome apparently consists of four dsRNAs 1-2.5?kbp in size. Here, we describe dsRNA incidence in the A. fumigatus isolates examined, their provenance and also note that on occasion individual isolates were infected with two groups of different dsRNAs.     

The Roles of Neutral Sphingomyelinases in Neurological Pathologies

The neutral sphingomyelinases (N-SMases) are a group of Mg²⁺-dependent enzymes with a pH optimum in the neutral range. N-SMases catalyze the conversion of sphingomyelin to ceramide and have been found particularly enriched in brain tissue. N-SMase activity has been implicated in many physiological and pathological processes affecting the brain and nervous system. In this review, we discuss the proposed functions of N-SMase with a particular emphasis on its role in neurological disorders, such as age-related neurodegeneration, Alzheimer’s disease, HIV-associated dementia, atherosclerosis, ischemia–reperfusion injury, and cancer.     

In vitro cytotoxic potential of Solanum nigrum against human cancer cell lines

Plants have natural products which use to possess antiproliferative potential against many cancers. In the present study, six isolated fractions (ethyl acetate, petroleum ether, chloroform, n-butanol, ethanol and aqueous) from Solanum nigrum were evaluated for their cytotoxic effect on different cell lines. Hepatic carcinoma cell line (HepG2), cervical cancer cell line (HeLa) and baby hamster kidney (BHK) used as normal non-cancerous cells were evaluated for cytotoxicity against isolated fractions. Cell viability assay was performed to evaluate the cytotoxicity of all fractions on different cell lines followed by the lactate dehydrogenase and vascular endothelial growth factor assays of most active fraction among all screened for cytotoxic analysis. HPLC analysis of most active fractions against cytotoxicity was performed to check the biological activity of compounds. Results displayed the potent cytotoxic activity of ethyl acetate fraction of S. nigrum against HepG2 cells with IC₅₀ value of 7.89 μg/ml. Other fractions exhibited potent anticancer activity against HepG2 cells followed by HeLa cells. Fractions in our study showed no cytotoxicity in BHK cells. Cytotoxic activity observed in our current study exposed high antiproliferative potential and activity of ethyl acetate fraction against HepG2 cells. The results demonstrated that S. nigrum fractions exhibited anticancer activity against hepatic and cervical cancer cell lines with non-toxic effect in normal cells. These results reveal significant potential of S. nigrum for the therapeutic of cancers across the globe in future.     

Geminivirus disease complexes: an emerging threat

Small circular single-stranded DNA satellites have recently been isolated from plants infected with whitefly-transmitted monopartite begomoviruses. The satellites, named DNA beta, depend on the helper viruses for their proliferation and, in turn, are required for helper virus accumulation and symptom expression. They are highly diverse yet retain an overall conserved structure with respect to potential coding regions and regulatory elements. The begomovirus-satellite disease complexes are associated with economically important diseases, and have been isolated from vegetable and fibre crops, ornamental plants and weeds throughout Africa and Asia. Their widespread distribution and diversity, coupled to the global movement of plant material and the dissemination of the whitefly vector, suggests that these disease complexes pose a serious threat to tropical and sub-tropical agro-ecosystems worldwide.     

Physiological responses and time-motion characteristics of 4-a-side small-sided game in young soccer players: the influence of different team formation methods

ABSTRACT: K?klü, Y, Ers?z, G, Alemdaro?lu, U, A???, A, and ?zkan, A. Physiological responses and time-motion characteristics of 4-A-side small-sided game in young soccer players: The influence of different team formation methods. J Strength Cond Res 26(11): 3118-3123, 2012-The purpose of this study was to examine the influence of different team formation methods on the physiological responses to and time-motion characteristics of 4-a-side small-sided games (SSG4) in young soccer players. Thirty-two young soccer players (age 16.2 ± 0.7 years; height 172.9 ± 6.1 cm; body mass 64.1 ± 7.7 kg) voluntarily participated in this study. Anthropometric measurements, technical tests, and maximum oxygen uptake (V[Combining Dot Above]O2max) tests were carried out on the players. The SSG4 teams were then created using 4 different methods: according to the coaches' subjective evaluation (CE), technical scores (TS), V[Combining Dot Above]O2max (AP), and V[Combining Dot Above]O2max multiplied by TSs (CG). The teams thus created played 4 bouts of SSG4 at 2-day intervals. During the SSG4, heart rate (HR) responses, distance covered, and time spent in HRmax zones were recorded. In addition, rating of perceived exertion (RPE) and blood lactate level (La) were determined at the end of the last bout of each SSG4. Percent of HRmax (%HRmax), La, and RPE responses during SSG4 were significantly higher for teams chosen according to AP and CG compared with that according to CE and TS (p < 0.05). In addition, teams chosen by AP and CG spent significantly more time in zone 4 (>90% HRmax ) and covered a greater distance in the high-intensity running zone (>18 km·h) than did teams formed according to TS. Moreover, AP teams covered significantly greater total distance than TS teams did (p < 0.05). In conclusion, to spend more time in both the high-intensity HR zone and the high-intensity running zone, the teams in SSG4 should be formed according to the players' V[Combining Dot Above]O2max values or the values calculated using both the V[Combining Dot Above]O2max and technique scores.     

Map-invariant spectral analysis for the identification of DNA periodicities

Many signal processing based methods for finding hidden periodicities in DNA sequences have primarily focused on assigning numerical values to the symbolic DNA sequence and then applying spectral analysis tools such as the short-time discrete Fourier transform (ST-DFT) to locate these repeats. The key results pertaining to this approach are however obtained using a very specific symbolic to numerical map, namely the so-called Voss representation. An important research problem is to therefore quantify the sensitivity of these results to the choice of the symbolic to numerical map. In this article, a novel algebraic approach to the periodicity detection problem is presented and provides a natural framework for studying the role of the symbolic to numerical map in finding these repeats. More specifically, we derive a new matrix-based expression of the DNA spectrum that comprises most of the widely used mappings in the literature as special cases, shows that the DNA spectrum is in fact invariable under all these mappings, and generates a necessary and sufficient condition for the invariance of the DNA spectrum to the symbolic to numerical map. Furthermore, the new algebraic framework decomposes the periodicity detection problem into several fundamental building blocks that are totally independent of each other. Sophisticated digital filters and/or alternate fast data transforms such as the discrete cosine and sine transforms can therefore be always incorporated in the periodicity detection scheme regardless of the choice of the symbolic to numerical map. Although the newly proposed framework is matrix based, identification of these periodicities can be achieved at a low computational cost.     

Why homocysteine-lowering therapy does not have beneficial effects on patients with cardiovascular disease?

Homocysteine is a sulfur-containing amino acid produced during the metabolism of methionine and elevated plasma levels of homocysteine have been linked to an increased risk of atherosclerosis and cardiovascular ischemic events by numerous authors. Several mechanisms by which elevated homocysteine impairs vascular function have been proposed including impairment of endothelial function and at least some of those mechanisms are induced via homocysteine-associated DNA hypomethylation. Oral administration of folic acid and B vitamins, required for remethylation of homocysteine to methionine, decreased plasma total homocysteine levels but clinical trials using folic acid and B vitamins did not confirm that the decreased plasma levels of homocysteine through diet or drugs may be paralleled by a reduction in cardiovascular risk. In our view a plausible explanation for the discordance between the epidemiologic studies and the results of the clinical trials may be related to the homocysteine-associated global DNA hypomethylation which cannot easily be reversed by homocysteine-lowering therapy.