Does prothymosin alpha affect the phosphorylation of elongation factor 2?

Prothymosin alpha is a small, acidic, essential nuclear protein that plays a poorly defined role in the proliferation and survival of mammalian cells. Recently, Vega et al. proposed that exogenous prothymosin alpha can specifically increase the phosphorylation of eukaryotic elongation factor 2 (eEF-2) in extracts of NIH3T3 cells (Vega, F. V., Vidal, A., Hellman, U., Wernstedt, C., and Domínguez, F. (1998) J. Biol. Chem. 273, 10147-10152). Using similar lysates prepared by four methods (detergent lysis, Dounce homogenization, digitonin permeabilization, and sonication) and three preparations of prothymosin alpha, one of which was purified by gentle means (the native protein, and a histidine-tagged recombinant prothymosin alpha expressed either in bacteria or in COS cells), we failed to find a response. A reconstituted system composed of eEF-2, recombinant eEF-2 kinase, calmodulin, and calcium was also unaffected by prothymosin alpha. However, unlike our optimized buffer, Vega's system included a phosphatase inhibitor, 50 mM fluoride, which when evaluated in our laboratories severely reduced phosphorylation of all species. Under these conditions, any procedure that decreases the effective fluoride concentration will relieve the inhibition and appear to activate. Our data do not support a direct relationship between the function of prothymosin alpha and the phosphorylation of eEF-2.     

Does antinerve growth factor affect isolated ileal contractility in rat?

This study investigates the effects of antinerve growth factor (anti-NGF) application on isolated ileal contractility in the rat. For this purpose, rats were divided into four groups. The control animals (n=8) received only intraperitoneal injection of an isotonic NaCl solution (i.p). Anti-NGF was daily administered intraperitoneally at the dose of 1 ng/g level in the first experimental group (n=8), and at doses of 10 ng/g (n=7) and 40 ng/g (n=7) in the second and third experimental groups, respectively. Seven days after the injections rats were sacrificed and ileum segments were isolated. Responses to acetylcholine (ACh) were evaluated by using standard Tyrode, double-calcium Tyrode and calcium-free Tyrode solutions. The average peak amplitude of ACh-induced contractions recorded in standard Tyrode solution was significantly decreased in all three experimental groups as compared to the control group (p 0.05). When double-calcium Tyrode solution was used as the perfusion medium, the responses to ACh were also lower in all anti-NGF applied groups as compared to its control group (p 0.05). Our results showed that the application of anti-NGF reduced the contractile responses of the rat isolated ileum apparently by decreasing the calcium influx from the extracellular medium.     

Does the circadian system regulate lactation?

Environmental variables such as photoperiod, heat, stress, nutrition and other external factors have profound effects on quality and quantity of a dairy cow's milk. The way in which the environment interacts with genotype to impact milk production is unknown; however, evidence from our laboratory suggests that circadian clocks play a role. Daily and seasonal endocrine rhythms are coordinated in mammals by the master circadian clock in the hypothalamus. Peripheral clocks are distributed in every organ and coordinated by signals from the master clock. We and others have shown that there is a circadian clock in the mammary gland. Approximately 7% of the genes expressed during lactation had circadian patterns including core clock and metabolic genes. Amplitude changes occurred in the core mammary clock genes during the transition from pregnancy to lactation and were coordinated with changes in molecular clocks among multiple tissues. In vitro studies using a bovine mammary cell line showed that external stimulation synchronized mammary clocks, and expression of the core clock gene, BMAL1, was induced by lactogens. Female clock/clock mutant mice, which have disrupted circadian rhythms, have impaired mammary development and their offspring failed to thrive suggesting that the dam's milk production was not adequate enough to nourish their young. We envision that, in mammals, during the transition from pregnancy to lactation the master clock is modified by environmental and physiological cues that it receives, including photoperiod length. In turn, the master clock coordinates changes in endocrine milieu that signals peripheral tissues. In dairy cows, it is clear that changes in photoperiod during the dry period and/or during lactation influences milk production. We believe that the photoperiod effect on milk production is mediated, in part by the 'setting' of the master clock with light, which modifies peripheral circadian clocks including the mammary core clock and subsequently impacts milk yield and may impact milk composition.     

Does salicylic acid regulate antioxidant defense system, cell death, cadmium uptake and partitioning to acquire cadmium tolerance in rice?

Salicylic acid (SA) may accelerate the cell death of cadmium-stressed roots to avoid cadmium (Cd) uptake by plants or may play positive roles in protecting the stressed roots from Cd-induced damage. To test these hypotheses, we performed a series of split-root hydroponic experiments with one-half of rice (Oryza sativa L. cv. Jiahua 1) roots exposed to 50 microM Cd and the other half not exposed. The objectives were to elucidate the effects of SA pretreatment on the time-dependent changes of H(2)O(2) levels in roots, antioxidant defense system in different organs, root cell death and the dynamic distribution of Cd in the plants. In the split-root system, a higher Cd uptake rate was observed in the Cd-stressed portions of roots compared with the treatment with the whole roots exposed to Cd. Furthermore, an appreciable amount of Cd was translocated from the Cd-exposed roots to the unexposed roots and trace amounts of Cd were released into the external solution. The split-root method also caused the two root portions to respond differently to Cd stress. The activities of major antioxidant enzymes (superoxide dismutase, SOD; peroxidase, POD; and catalase, CAT) were significantly suppressed in the Cd-treated roots, hence leading to H(2)O(2) burst, lipid peroxidation, cell death and growth inhibition. By contrast, in the non-Cd-treated roots, the activities of enzymes (SOD, CAT, and POD) and root growth were persistently stimulated during the experimental period. The H(2)O(2) accumulation and lipid peroxidation were also induced in the non-Cd-treated roots, but they were significantly lower than those of the Cd-treated roots. The concentrations of glutathione (GSH) and non-protein thiols (NPT) in the Cd-treated roots were significantly higher than those of the untreated roots. SA pretreatment elevated enzymatic and non-enzymatic antioxidants, and the concentrations of GSH and NPT in roots and shoots, hence leading to alleviation of the oxidative damage as indicated by the lowered H(2)O(2) and MDA levels. Furthermore, SA pretreatment mitigated the Cd-induced growth inhibition in both roots and shoots and increased transpiration compared with non-SA-pretreatment under Cd exposure. It is concluded that Cd can be partly transferred from the Cd-exposed roots to Cd-unexposed roots and that cell death can be accelerated in the Cd-stressed roots in response to Cd stress. The SA-enhanced Cd tolerance in rice can be attributed to SA-elevated enzymatic and non-enzymatic antioxidants and NPT, and to SA-regulated Cd uptake, transport and distribution in plant organs.     

Does the insulin-like growth factor system interact with prostaglandins and proinflammatory cytokines during neurodegeneration?

Prostaglandins and proinflammatory cytokines are implicated in the etiology of neurodegenerative diseases, such as Alzheimer's disease. Signaling cascades initiated by these factors may result in reactive oxygen species generation and cell death. The insulin-like growth factors (IGF) are ubiquitous polypeptides involved in all aspects of growth and development. Additionally, the IGF are regarded as survival factors that display potent antiapoptotic activity. Interfering with IGF production, distribution, or signaling may result in greater susceptibility to apoptotic stimuli. In neurodegenerative conditions, the IGF appear to be antagonized by prostaglandins and proinflammatory cytokines. In this review, the relationship among specific prostaglandins, the proinflammatory factors, tumor necrosis factor, interleukin-1, and interleukin-6, and the IGF system will be investigated.     

Does the intestinal bifidobacterial colonisation affect bacterial translocation?

The aim of this work was to investigate the possible role of the intestinal anaerobic flora (especially bifidobacteria) in regulating bacterial translocation (BT) which can be defined as the passage of intestinal microbes through the mucosa to internal organs. Default in BT regulation concurs with pathogenesis of sepsis in various human conditions, such as acute pancreatitis, cirrhosis, necrotising enterocolitis or multiple organ failure. The intestinal flora was studied in human flora associated mice (HF mice) and BT was quantified in Peyer's patches (PP), blood, spleen, liver and lungs. HF mice displayed a heterogenic intestinal colonisation with bifidobacteria. High colonisation of both caecum and colon by bifidobacteria led to a poorer bacterial contamination of blood, liver and lungs. Moreover, ileal, caecal and colonic bifidobacterial counts negatively correlated with the bacterial dissemination (number of contaminated organs per mouse). In contrast, Bacteroides fragilis group counts positively correlated with bacteraemia, lungs contamination or bacterial dissemination. Additionally, clostridia localised in the colon affected bacterial uptake by PP and lungs contamination as indicated by positive correlations between bacterial populations in these respective locations. These results indicate that bifidobacteria, when established in high counts, reduced BT to liver, blood and lungs, whereas B. fragilis group favoured the bacterial passage. Clostridia established in the distal ileum also seemed to favour BT to lungs. The manipulation of the bacterial flora to optimise the regulatory effect on BT should therefore focus on the selective promotion of bifidobacteria and avoid an increase in potentially detrimental populations such as B. fragilis group and clostridia.     

Does androstenol affect emotion?

Men and women read an erotic literary passage while being exposed to the odor of androstenol, rose water, or a control. Subjects then rated the intensity of eleven different emotions. Little evidence was found to support the hypothesis that androstenol affects emotional responsiveness in either men or women.     

Microbe-induced T cell apoptosis: subversion of the host defense system?

Cells of multicellular organisms are equipped with a self destruction program called apoptosis to ensure homeostasis of the organism. Contraction of the lymphocyte compartment following recovery from an infection is controlled by this mechanism. But apoptosis of lymphocytes might be an Achilles tendon accessible to microbes to subvert the immune system. Evidence is cumulating that microbes use this mechanism to destroy microbe-specific T cells. We present an overview of microbe-induced T cell apoptosis discussing the consequences for the pathogenesis of microbial infection. The conventional role of lymphocytes during infection is to impose apoptotic threat to infected cells, the subject of this review highlights the opposite, lymphocytes as targets of microbe-induced death.     

Does carnosine possess direct antioxidant activity?

• 1.1. A brief review of development of ideas of the antioxidant activity of carnosine and related compounds is presented.
• 2.2. An analysis of the behaviour of carnosine in different models of free radical chain reactions shows that carnosine is a potent hydrophylic antioxidant of a direct non-enzymatic action.
• 3.3. It is characteristic of the higher activity of interaction with active hydroxyl radical.
• 4.4. However the known biological effects of carnosine cannot be explained only by its anti-oxidant properties.

     

Does sphingomyelin inhibit the erythrocyte anion transport system?

The anion transport protein of the human erythrocyte membrane, band 3, was incorporated into unilamellar sphingomyelin vesicles. The vesicles showed a rapid sulfate efflux which could be inhibited by specific inhibitors of the erythrocyte anion transport system. All band 3 molecules contributing to the inhibitor-sensitive flux component were arranged 'right-side-out'. The turnover number of the transport protein for sulfate transport was virtually identical to that in phosphatidylcholine bilayers and around 6 times larger than in human erythrocyte membranes. Thus, in contrast to other claims, sphingomyelin does not inhibit the erythrocyte anion transport system.     

Does neonatal gonadectomy affect the sexual differentiation of quail?

This experiment was designed to determine the contribution, if any, of posthatching gonadal hormones to sexual differentiation of behavior in Japanese quail (Coturnix coturnix japonica). Males and females were gonadectomized or sham-operated (controls) prior to age 7 days posthatching. At age 4-9 weeks controls were gonadectomized. All birds were then given 2 weeks of testosterone propionate injections and tested for sexual behavior with female partners. Neonatally gonadectomized females exhibited more male-typical copulatory behavior than control females, but this effect was not statistically significant. Neonatal gonadectomy had no effect on males, and neonatally gonadectomized males exhibited significantly more male-typical copulatory behavior than neonatally gonadectomized females. Although the process of sexual differentiation may extend to a minor degree into the posthatching period in females, nonetheless it is largely complete at hatching in this species.     

Does the fetal genotype affect maternal physiology during pregnancy?

Conventional wisdom states that associations between fetal growth and diseases in pregnancy, such as pregnancy-induced hypertension (PIH) and gestational diabetes (GDM), result from effects of the mother's genotype or environment acting on her physiology which subsequently affect the fetus. However, recent evidence from human mothers carrying macrosomic offspring with Beckwith Wiedemann syndrome and pregnant mice carrying p57(kip2)-null offspring suggest that variation in the fetal genome can modify maternal physiology to increase fetal nutrient delivery and optimise growth. These are some of the first documented examples of such effects, whereby the genome of one individual directly affects the physiology of another related individual from the same species. We propose that this mechanism is involved in the aetiology of PIH and GDM.     

Efficacy of DL-α lipoic acid against systemic inflammation-induced mice: antioxidant defense system

Inflammation can activate macrophages or monocytes and sequentially release several inflammatory cytokines and reactive oxygen species (ROS). Oxidative stress-induced acute inflammatory response plays an important role in several diseases. This study was designed to investigate the prophylactic effect of the antioxidant lipoic acid (LA) during inflammation-induced mice. Mice were divided in to three groups (n = 8 in each): control, systemic inflammation, and LA treated mice with systemic inflammation. Results show that ROS was significantly higher in lymphocytes, hepatocytes, and astrocytes (P < 0.05) of inflammation induced mice when compared with control but no significant changes were observed in the LA treated group. Increased levels of lipid peroxidation (LPO) and decreased activities of oxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione, and ATPase were observed in the inflammation-induced mice, which returned to near normalcy following LA therapy. In vitro study has shown that LA treatment not only suppresses the increased LPO levels but also inhibits the lipid break down resulting from autoxidation. In addition, increased immunoreactivity of the astrocyte marker glial fibrillary acidic protein (GFAP) was observed in the neocortex region of inflammation-induced mice, whereas nuclear factor kappa B p65 (NFkappaB) immunoreactivity was observed in both the neocortex and liver of the same group which were effectively controlled by LA therapy suggesting that LA can efficiently manage systemic inflammation.