Stereotaxic Administration of 1-Methyl-4-Phenylpyridinium Ion (MPP+) Decreases Striatal Fructose 2,6-Bisphosphate in Rats

Abstract: The Stereotaxic administration of 1-methyl-4-phenylpyridinium ion (MPP⁺) into the neostriatum of male rats caused a lesion that resulted in a large dose-dependent loss of striatal fructose 2,6-bisphosphate; initial values were restored 5 days after the treatment. This effect was not protected by systemic administration of MK-801 or by nitroarginine. The content of hexose 6-phosphates and ATP was also reduced by MPP⁺ treatment, whereas lactate was increased. Biochemical and histological results suggested that MPP⁺ caused a nonselective cell death, followed by a pronounced astroglial response, parallel to fructose 2, 6-bisphosphate recovery. The Stereotaxic administration of rotenone showed a different time effect on fructose 2,6-bisphosphate cerebral content, with a significantly faster recovery. These results indicate that cerebral fructose 2,6-bisphosphate may be a sensitive metabolite related to brain damage caused by potent neurotoxins such as MPP⁺. On the other hand, they show that MPP⁺ acts in the brain through a quick, strong cytotoxic mechanism, which probably involves mechanisms other than mitochondria! chain blockage     

Lca certification according to iso 14.040: First experience

The International Journal of Life Cycle Assessment -     

Does measuring early basal serum follicular lutinising hormone assist in predicting In vitro fertilization (IVF)/Intracytoplasmic sperm injection (ICSI) outcome?

Background  

The aim was to examine the correlation of early follicular serum lutinising hormone (LH) and the clinical outcome of assisted reproduction technique (ART).     

A Paradigm of Uphill Running

The biomechanical management of bioenergetics of runners when running uphill was investigated. Several metabolic and mechanical variables have been studied simultaneously to spread light on the locomotory strategy operated by humans for effective locomotion. The studied variables were: heart rate, heart rate variability, oxygen intake and blood lactate, metabolic cost, kinematics, ground reaction force and muscular activity. 18 high-level competitive male runners ran at 70% VO_2max on different uphill slope conditions: 0%, 2% and 7%. Modifications were significant in almost all variables studied, and were more pronounced with increasing incline. Step frequency/length and ground reaction force are adjusted to cope with both the task of uphill progression and the available (limited) metabolic power. From 0% to 7% slope, step frequency and ground reaction force and metabolic cost increased concurrently by 4%, 12% and 53%, respectively (with a 4% step length decrease as well). It is hypothesised that this biomechanical management is allowed by an environment-body communication performed by means of specific muscular activity.     

The thiazole derivative CPTH6 impairs autophagy

We have previously demonstrated that the thiazole derivative 3-methylcyclopentylidene-[4-(4′-chlorophenyl)thiazol-2-yl]hydrazone (CPTH6) induces apoptosis and cell cycle arrest in human leukemia cells. The aim of this study was to evaluate whether CPTH6 is able to affect autophagy. By using several human tumor cell lines with different origins we demonstrated that CPTH6 treatment induced, in a dose-dependent manner, a significant increase in autophagic features, as imaged by electron microscopy, immunoblotting analysis of membrane-bound form of microtubule-associated protein 1 light chain 3 (LC3B-II) levels and by appearance of typical LC3B-II-associated autophagosomal puncta. To gain insights into the molecular mechanisms of elevated markers of autophagy induced by CPTH6 treatment, we silenced the expression of several proteins acting at different steps of autophagy. We found that the effect of CPTH6 on autophagy developed through a noncanonical mechanism that did not require beclin-1-dependent nucleation, but involved Atg-7-mediated elongation of autophagosomal membranes. Strikingly, a combined treatment of CPTH6 with late-stage autophagy inhibitors, such as chloroquine and bafilomycin A1, demonstrates that under basal condition CPTH6 reduces autophagosome turnover through an impairment of their degradation pathway, rather than enhancing autophagosome formation, as confirmed by immunofluorescence experiments. According to these results, CPTH6-induced enhancement of autophagy substrate p62 and NBR1 protein levels confirms a blockage of autophagic cargo degradation. In addition, CPTH6 inhibited autophagosome maturation and compounds having high structural similarities with CPTH6 produced similar effects on the autophagic pathway. Finally, the evidence that CPTH6 treatment decreased α-tubulin acetylation and failed to increase autophagic markers in cells in which acetyltransferase ATAT1 expression was silenced indicates a possible role of α-tubulin acetylation in CPTH6-induced alteration in autophagy. Overall, CPTH6 could be a valuable agent for the treatment of cancer and should be further studied as a possible antineoplastic agent.     

Computational Fact Checking from Knowledge Networks

Traditional fact checking by expert journalists cannot keep up with the enormous volume of information that is now generated online. Computational fact checking may significantly enhance our ability to evaluate the veracity of dubious information. Here we show that the complexities of human fact checking can be approximated quite well by finding the shortest path between concept nodes under properly defined semantic proximity metrics on knowledge graphs. Framed as a network problem this approach is feasible with efficient computational techniques. We evaluate this approach by examining tens of thousands of claims related to history, entertainment, geography, and biographical information using a public knowledge graph extracted from Wikipedia. Statements independently known to be true consistently receive higher support via our method than do false ones. These findings represent a significant step toward scalable computational fact-checking methods that may one day mitigate the spread of harmful misinformation.     

Connectivity and information transfer in flow networks: Two magic numbers in ecology?

An ecosystem can be visualized as a graph of certain preassigned trophic compartments; these nodes are then mutually connected through the internal exchanges of material and energy. The mathematical theory of information can be applied to such a graph in order to define two relevant indices: a measure of connectivity (the entropy H of the connections) and a measure of the degree of the “energetic” specialization (the internal transfer of informationI). The computation of these indices in stationary real cases suggests that the observed complexity of ecosystems is conditioned by two competing effects. The first can be interpreted as a “thermodynamical” principle related to the unavoidable irreversibility taking place inside the system, whereas the second can be taken as a “biological” principle concerned with the selection of some particular interactions: those which maximize the information circulating between the compartments.     

Chromosomal aberrations and micronuclei induced in rat and mouse bone marrow cells by sodium nitrate

The genotoxicity of several anthraquinone compounds metabolically related to aflatoxin B1 was examined by means of the hepatocyte primary culture (HPC)/DNA repair test and the Salmonella microsome mutagenesis test, and compared to versicolorins A and B which are potent mutagenic and genotoxic intermediates of the aflatoxin biosynthetic pathway. 6,8-O-Dimethyl-versicolorins A, B and 6-deoxyversicolorin A were found to be strongly mutagenic and genotoxic. Genotoxicity of versicolorin A and 6,8-O-dimethylversicolorin A was stronger than that of versicolorin B and 6,8-O-dimethylversicolorin B, respectively, in the HPC/DNA repair test. Nidurufin and norsolorinic acid, which do not possess a bisfuran ring, exhibited questionable activities for mutagenicity and no genotoxicity. It is suspected that 6,8-O-dimethylversicolorins A, B and 6-deoxyversicolorin A as well as versicolorins A and B are genotoxic carcinogens.