Long Term Use of HU210 Adversely Affects Spermatogenesis in Rats by modulating the Endocannabinoid System

Recent societal acceptance of cannabinoids as recreational and therapeutic drugs has posed a potential hazard to male reproductive health. Mammals have a highly sophisticated endogenous cannabinoid (ECS) system that regulates male (and female) reproduction and exo-cannabinoids may influence it adversely. Therefore it is imperative to determine their effects on male reproduction so that men can make informed choices as to their use. Here, an animal model was used to administer HU210, a synthetic analogue of ?9-tetrahydrocannabinol (THC) and potent cannabinoid receptor (CB) agonist to determine its effects on reproductive organ weights, spermatogenesis, testicular histology and sperm motility. Its effects on the physiological endocannabinoid system were also investigated. Spermatogenesis was markedly impaired with reductions in total sperm count after 2 weeks of exposure. Spermatogenic efficiency was depleted, and Sertoli cell number decreased as exposure time increased with seminiferous tubules showing germ cell depletion developing into atrophy in some cases. Sperm motility was also adversely affected with marked reductions from 2 weeks on. HU210 also acted on the sperm’s endocannabinoid system. Long term use of exo-cannabinoids has adverse effects on both spermatogenesis and sperm function. These findings highlight the urgent need for studies evaluating the fertility potential of male recreational drug users.

Measurement and modelling of perceived slant in surfaces represented by freely viewed line drawings

Simple pictures under everyday viewing conditions evoke impressions of surfaces oriented in depth. These impressions have been studied by measuring the slants of perceived surfaces, with probes (rotating arrowheads) designed to respect the distinctive character of depicted scenes. Converging arguments indicated that the perceived orientation of the probes was near theoretical values. A series of experiments showed that subjects formed well-defined impressions of depicted surface orientation. The literature suggests that perceived objects might be flattened', but that was not the general rule. Instead, both mean slant and uncertainty fitted models in which slant estimates are derived in a relatively straightforward way from local relations in the picture. Simplifying pictures tended to make orientation estimates less certain, particularly away from the natural anchor points (vertical and horizontal). The shape of the object affected all aspects of the observed-object/percept relationship. Individual differences were large, and suggest that different individuals used different relationships as a basis for their estimates. Overall, data suggest that everyday picture perception is strongly selective and weakly integrative. In particular, depicted slant is estimated by finding a picture feature which will be strongly related to it if the object contains a particular regularity, not by additive integration of evidence from multiple directly and indirectly relevant sources.

Change in UK construction: Moving towards supply chain collaboration

There has been an increasing highlight of supply chain collaboration in UK construction. However, few studies have provided evidence for the current status. Based on the analysis of over 100 questionnaire responses in this research, it is found that the UK construction industry as a whole is experiencing an important change and moving towards supply chain collaboration. On the other hand, an unbalance is found for the change movement. In addition to the questionnaire survey, a series of expert interviews help to explore the specific characteristics of supply chain collaboration in construction and provide practical implications for collaboration strategy implementation.

The Sound of Becoming: Moving Towards a Virtual Music

In 1985 Jacques Attali proposed a new modality for music. He suggests that there be “not a new music, but a new way of making music... a radically new form of the insertion of music into communication” (Attali 134). What Attali foretold has become a firm reality in contemporary musical practice. One has only to look at any current musical activity to encounter work that relies heavily on real-time interaction and dynamic generation and/or modification of materials. But why is this ontologically different ‘mode of essentially interactive and transformative existence’ (Ziarek 195), this ‘new way of making music’, so attractive to contemporary artists? What is motivating artists to abandon a production model in favor of a model of real-time interactive exploration? I will argue that at the foundation of this new artistic ontology lies Deleuze’s concept of the virtual. It is a recognition of the virtual power of music, that music making can be an act of invention, a process where one can discover something never before experienced.

Activation of extracellular signal-regulated kinase in proliferative glomerulonephritis in rats

Multiple extracellular mitogens are involved in the pathogenesis of proliferative forms of glomerulonephritis (GN), In vitro studies demonstrate the pivotal role of extracellular signal-regulated kinase (ERK) in the regulation of cellular proliferation in response to extracellular mitogens. In this study, we examined whether this kinase, as a convergence point of mitogenic stimuli, is activated in proliferative GN in vivo, Two different proliferative forms of anti-glomerular basal membrane (GEM) GN in rats were induced and whole cortical tissue as well as isolated glomeruli examined using kinase activity assays and Western blot analysis, Administration of rabbit anti-rat GEM serum to rats, preimmunized with rabbit IgG, induced an accelerated crescentic anti-GEM GN. A significant increase in cortical, and more dramatically glomerular ERK activity was detected at 1, 3, and 7 d after induction of GN, Immunization of Wistar-Kyoto rats with bovine GEM also induced a crescentic anti-GBM GN with an increase of renal cortical ERK activity after 4, 6, and 8 wk, ERK is phosphorylated and activated by the MAP kinase/ERK kinase (MEK), We detected a significant increase in the expression of glomerular MEK in the accelerated form of anti-GEM CN, providing a possible mechanism of long-term activation of ERK in this disease model, In contrast to ERK, activation of stress-activated protein kinase was only detectable at early stages of proliferative GN, indicating these related kinases to serve distinct roles in the pathogenesis of GN, Our observations point to ERK as a putative mediator of the proliferative response to immune injury in GN and suggest that upregulation of MEK is involved in the long-term regulation of ERK in vivo.

Vitamin B-6 deficiency in rats reduces hepatic serine hydroxymethyltransferase and cystathionine beta-synthase activities and rates of in vivo protein turnover, homocysteine remethylation and transsulfuration

Vitamin B-6 deficiency causes mild elevation in plasma homocysteine, but the mechanism has not been clearly established. Serine is a substrate in one-carbon metabolism and in the transsulfuration pathway of homocysteine catabolism, and pyridoxal phosphate (PLP) plays a key role as coenzyme for serine hydroxymethyltransferase (SHMT) and enzymes of transsulfuration. In this study we used [H-2(3)]serine as a primary tracer to examine the remethylation pathway in adequately nourished and vitamin B-6-deficient rats pi and 0.1 mg pyridoxine (PN)/kg diet]. [H-2(3)]Leucine and [1-C-13]methionine were also used to examine turnover of protein and methionine pools, respectively, All tracers were injected intraperitoneally as a bolus dose, and then rats were killed (n = 4/time point) after 30, 60 and 120 min. Rats fed the low-PN diet had significantly lower growth and plasma and liver PLP concentrations, reduced liver SHMT activity, greater plasma and liver total homocysteine concentration, and reduced liver S-adenosylmethionine concentration. Hepatic and whole body protein turnover were reduced in vitamin B-6-deficient rats as evidenced by greater isotopic enrichment of [H-2(3)]leucine. Hepatic [H-2(2)]methionine production from [H-2(3)]serine via cytosolic SHMT and the remethylation pathway was reduced by 80.6% in vitamin B-6 deficiency. The deficiency did not significantly reduce hepatic cystathionine-beta-synthase activity, and in vivo hepatic transsulfuration flux shown by production of [H-2(3)]cysteine from the [H-2(3)]serine increased over twofold. In contrast, plasma appearance of [H-2(3)]cysteine was decreased by 89% in vitamin B-6 deficiency. The rate of hepatic homocysteine production shown by the ratio of [1-C-13]homocysteine/[1-C-13]methionine areas under enrichment vs. time curves was not affected by vitamin B-6 deficiency. Overall, these results indicate that vitamin B-6 deficiency substantially affects one-carbon metabolism by impairing both methyl group production for homocysteine remethylation and flux through whole-body transsulfuration.