Does toxoplasmosis cause DNA damage? An evaluation in isogenic mice under normal diet or dietary restriction

Toxoplasmosis is an anthropozoonotic widespread disease, caused by the coccidian protozoan parasite Toxoplasma gondii. Since there are no data regarding the genotoxicity of the parasite in vivo, this study was designed to evaluate the genotoxic potential of the toxoplasmosis on isogenic mice with normal diet or under dietary restriction and submitted to a treatment with sulfonamide (375 microg/kg per day). DNA damage was assessed in peripheral blood, liver and brain cells using the comet assay (tail moment). The results for leucocytes showed increases in the mean tail moment in mice under dietary restriction; in infected mice under normal diet; in infected, sulfonamide-treated mice under normal diet; in infected mice under dietary restriction and in infected sulfonamide-treated mice under dietary restriction. In liver and brain cells, no statistically significant difference was observed for the tail moment. These results indicated that dietary restriction and T. gondii were able to induce DNA damage in peripheral blood cells, as detected by the comet assay.     

Does sodium restriction lower blood pressure?

Data from 13 randomised trials on the effect of sodium restriction on blood pressure were analysed. The hypotensive effect of sodium restriction was found to be small and restricted largely to systolic blood pressure, which fell by an average of 3.6 mm Hg (range 0.5-10.0 mm Hg). The reduction increased with age and in those with higher blood pressure. Sodium restriction therefore seems to be of limited use in those who are most eligible for non-pharmacological treatment of high blood pressure--namely, young patients with mild hypertension.     

Does caffeine induce dominant lethal mutations in mice?

Summary The problem of mutagenic activity of caffeine (1-3-7-trimethylxanthine) in man became more and more urgent because it is; first, one of the most frequently used stimulants in beverages and drugs and; second, recently several contradictory reports have been published [37, 29, 1, 43] which were followed up in public with great interest. We, therefore, tested the spermatogenesis of mice with the method of induction of dominant lethal mutations [42] in order to find a mutagenic effect, and by fractionating the spermatogenesis in eight breeding groups to detect some sensitive stages after a single treatment with a high caffeine dose. The animals used were of the C3H inbred strain of mice, the dose just tolerated by these animals was 0.25 g caffeine/kg body weight. Two experiments were carried out under same conditions with 29 males treated and 10 males in the control group. 373 pregnant females fertilized by the treated males showed among their 3495 implants 15% dead implantations while 201 females fertilized by the control males had 2139 implants, 13.6% of which died during pregnancy. This slight difference does not indicate any mutagenic function of caffeine on the spermatogenesis of mice as a whole. The tested stages of spermatogenesis revealed no sensitivity. A slight increase in pseudopregnancy (P0.007) could be observed, which might be physiologically caused. Copulation frequency was considerably decreased, especially in the first week after treatment.With the support of the Deutsche Forschungsgemeinschaft.     

Does Rbmy have a role in sperm development in mice?

The Y(d1) deletion in mice removes most of the multi-copy Rbmy gene cluster that is located adjacent to the centromere on the Y short arm (Yp). XY(d1) mice develop as females because Sry is inactivated, probably because it is now juxtaposed to centromeric heterochromatin. We have previously produced XY(d1)Sry transgenic males and found that they have a substantially increased frequency of abnormal sperm. Staining of testis sections with a polyclonal anti-RBMY antibody appeared to show a marked decrease of RBMY protein in the spermatids of XY(d1)Sry males compared to control males, which led us to suggest that this may be responsible for the increase in sperm anomalies. In the current study we sought to determine whether augmenting Rbmy expression specifically in the spermatids of XY(d1)Sry males would ameliorate the sperm defects. An expressing Rbmy transgene driven by the spermatid-specific mouse protamine 1 promotor (mP1Rbmy) was therefore introduced into XY(d1)Sry males. This failed to reduce the frequency of abnormal sperm. In the course of this study, a new RBMY antibody was generated that, in contrast to the original antibody, failed to detect RBMY in spermatid stages by immunostaining. The lack of RBMY was confirmed by western blotting of lysates from purified round spermatids and elongating spermatids. The implications of these results for the proposed role for RBMY in sperm development are discussed.     

Prevention of mammary tumorigenesis by intermittent caloric restriction: does caloric intake during refeeding modulate the response?

Chronic caloric restriction (CCR) prevents mammary tumorigenesis in rodents, but a protective effect for intermittent caloric restriction (ICR) is less well documented. We recently reported that ICR reduced mammary tumor (MT) incidence of mouse mammary tumor virus-transforming growth factor (MMTV-TGF)-alpha mice to a greater extent than did CCR. Here, we repeated this protocol and obtained serum and tissue samples. Ad libitum (AL) MMTV-TGF-alpha mice were fed AIN-93M diet. Beginning at 10 weeks of age, ICR mice received isocaloric AIN-93M-mod diet (2-fold increases in protein, fat, vitamins, and minerals) at 50% of ad libitum for 3 weeks followed by 3 weeks refeeding with AIN-93M diet. CCR mice were pair-fed AIN-93M:AIN-93M-mod (2:1) matching intakes for restriction/refeeding cycles. Mice were sacrificed for MT size, at 79 (end of 12th restriction) or at 80 (1 week after 12th refeeding) weeks of age. AL and ICR-80 mice had heavier body weights than ICR-79 and CCR mice (P < 0.0001). Cumulative food intakes of ICR and CCR mice were reduced 12% and 15% versus AL mice (P < 0.0001). However, ICR mice consumed significantly (P < 0.0001) more food than did AL mice during refeeding. MT incidence was 84%, 13%, and 27% for AL, ICR, and CCR mice, respectively. MT weight (P < 0.0011) and number (P < 0.01) were higher for AL mice compared with ICR and CCR mice. AL and ICR-80 mice had similar serum IGF-I levels, but only AL values were higher than those of ICR-79 and CCR mice (P < 0.0017). ICR mice had more MT DNA breaks compared with AL and CCR mice, suggesting enhanced apoptosis (P < 0.02). AL mice had higher mammary fat pad ObR and ObRb leptin receptor mRNA expression than did ICR and CCR mice (P < 0.001), but there was no effect on MTs. These results confirm that ICR prevents development of MTs to a greater extent than does CCR, although "overeating" during refeeding may compromise this protection.     

Increasing longevity through caloric restriction or rapamycin feeding in mammals: common mechanisms for common outcomes?

Significant extension of lifespan in important mammalian species is bound to attract the attention not only of the aging research community, but also the media and the wider public. Two recent papers published by Harrison et al. (2009) in Nature and by Colman et al. (2009) in Science report increased longevity of mice fed with rapamycin and of rhesus monkeys undergoing caloric restriction, respectively. These papers have generated considerable debate in the aging community. Here we assess what is new about these findings, how they fit with our knowledge of lifespan extension from other studies and what prospects this new work holds out for improvements in human longevity and human health span.     

Does quantum mechanics play a non-trivial role in life?

There have been many claims that quantum mechanics plays a key role in the origin and/or operation of biological organisms, beyond merely providing the basis for the shapes and sizes of biological molecules and their chemical affinities. These range from Schr?dinger's suggestion that quantum fluctuations produce mutations, to Hameroff and Penrose's conjecture that quantum coherence in microtubules is linked to consciousness. I review some of these claims in this paper, and discuss the serious problem of decoherence. I advance some further conjectures about quantum information processing in bio-systems. Some possible experiments are suggested.     

Does wild boar rooting affect livestock grazing areas in alpine grasslands?

Interactions between traditional livestock management practices and wildlife activities are important in the conservation of many mountain ecosystems including the summer rangelands in the Spanish Central Pyrenees, where rooting by wild boar (Sus scrofa) is a large disturbance that can reduce the amount of area available to grazing livestock. This study explored the likely impact of wild boar rooting on Pyrenean grasslands. It quantified the extent of wild boar rooting in livestock grazing areas and determined whether wild boars selected or avoided areas depending on the type of livestock and stocking rates. Wild boar rooting affected 16% of livestock grazing area and occurred in sites that were grazed by cattle, rather than by sheep. In addition, a preference for areas that had intermediate stocking rates was found. The relationship between the increase in the number of wild boars and trends in livestock management suggests that the extent of wild boar rooting will increase especially in cattle grazing areas, and therefore, the area available for cattle grazing in Pyrenean mountain rangelands would decrease significantly.     

The thioredoxin system in aging muscle: key role of mitochondrial thioredoxin reductase in the protective effects of caloric restriction?

Cellular redox balance is maintained by various antioxidative systems. Among those is the thioredoxin system, consisting of thioredoxin, thioredoxin reductase, and NADPH. In the present study, we examined the effects of caloric restriction (2 mo) on the expression of the cytosolic and mitochondrial thioredoxin system in skeletal muscle and heart of senescent and young rats. Mitochondrial thioredoxin reductase (TrxR2) is significantly reduced in aging skeletal and cardiac muscle and renormalized after caloric restriction, while the cytosolic isoform remains unchanged. Thioredoxins (mitochondrial Trx2, cytosolic Trx1) are not influenced by caloric restriction. In skeletal and cardiac muscle of young rats, caloric restriction has no effect on the expression of thioredoxins or thioredoxin reductases. Enforced reduction of TrxR2 (small interfering RNA) in myoblasts under exposure to ceramide or TNF-alpha causes a dramatic enhancement of nucleosomal DNA cleavage, caspase 9 activation, and mitochondrial reactive oxygen species release, together with reduced cell viability, while this TrxR2 reduction is without effect in unstimulated myoblasts under basal conditions. Oxidative stress in vitro (H2O2 in C2C12 myoblasts and myotubes) results in different changes: TrxR2, Trx2, and Trx1 are induced without alterations in the cytosolic thioredoxin reductase isoforms. Thus aging is associated with a TrxR2 reduction in skeletal muscle and heart, which enhances susceptibility to apoptotic stimuli but is renormalized after short-term caloric restriction. Exogenous oxidative stress does not result in these age-related changes of TrxR2.     

Symbolic communication in wild chimpanzees?

The language abilities of captive chimpanzees give rise to the question of the existence and use of similar capabilities in wild chimpanzees. In Taï forest, wild chimpanzees seem to use drumming on buttressed trees to convey information an changes of travel direction, resting periods or both information combined. This communication system is iconic and relies on some arbitrariness. Emergence of symbol-like communication in wild chimpanzees seems mainly dependent on a low visibility environment, a high predation pressure and a large group of males.     

Does life consistently maximise energy intensity?

We propose that a basic biological imperative of all organisms is to maximise energy (E) intensity, defined as the average rate of energy use per unit area of the Earth's surface. The dominant organism in any given environment is predicted to be that exerting the greatest E intensity regardless of evolutionary origin. Our ‘theory of biological E intensity’ thus explains variation in life form in terms of adaptations as opposed to accidents of biological history. It defines the competitive criterion in all metabolic pathways and industrial processes as the average rate of kinetic energy use, excluding heating but including all directed biological kinesis at scales up to the whole organism. A suggested unit for E intensity is joules per square meter per year. Because catalysts are crucial to extremely rapid use of energy (and therefore maximisation of E intensity), catalytic nutrient elements can be viewed as the ultimate means of life. It follows that a common denominator of all dominant organisms would be the acquisition of an optimal catalytic formula as determined by concentrations and ratios of C, H, O, N, S, Na, Mg, P, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Se, Mo, Cd, I, W, and Hg. The likely local shortages of various of these elements can theoretically be alleviated by various changes in the size, shape, and/or behaviour of organisms, depending on the environment. Thus, the availability, and potential for supplementation, of catalytic elements would be the ultimate basis for adaptation, largely determining which life form dominates in any particular location. The theory predicts the following. (1) In nutrient‐rich environments offering the optimal catalytic formula, dominant organisms will be microbes. This is because microbes, and prokaryotes in particular, excel in E intensity through rapid biomolecular turnover, enabling them to usurp resources despite minimising biomass, complexity, and information. (2) Where the environment is catabolically dystrophic (i.e. scarce in certain nutrients required for catabolism), macrobes (e.g. humans and trees) will be superior competitors because they can collect and supplement nutrients and thereby approach the optimal catalytic formula. This enables macrobes, despite having considerably slower metabolism per unit body mass, to enhance E intensity relative to competing microbes constrained by catabolic dystrophy. Finally, (3) where the environment is anabolically dystrophic (i.e. scarce in certain nutrients required for anabolism) microbes will again dominate because biomolecular turnover can be relatively free from constraint given the limited fuel available. We suggest that an important and overlooked way to achieve power is to reuse energy, and that all organisms maximise E intensity by converting chemical potential energy (i.e. in fuel) into circuits of electromagnetic energy comprising electric charge, photons, and excited electrons. Because space and time merge subatomically, these electromagnetic circuits represent a concentration in spacetime of energy that (1) is concurrently kinetic and static, hence available for immediate use yet also conserved with minimal dissipation, and (2) ultimately promotes catalysis, which we assert is the primary biological tactic for maximising E intensity and thus fitness.     

Does feeding area restriction inhibit social learning of toxic weed ingestion in cattle?

Social learning from peers can trigger herd-wide intoxication with white locoweed (Oxytropis sericea), an alkaloid-synthesizing herbaceous legume that grows on rangelands of western North America. We conducted an experiment to test the hypothesis that restriction of the area allocated to animals to feed in would inhibit social facilitation of locoweed ingestion in yearling heifers. Eight heifers that avoided white locoweed (LA) and eight heifers that readily consumed it (LE) were selected from a pool of 40 cross-bred heifers and were randomly assigned to the social facilitation or social interference treatment groups. We conducted 200 10-min feeding trials in three 5-day phases (pre-treatment, treatment, post-treatment) during which animals were presented with a set of bowls arrayed in a test arena, some of which contained ground wheat straw and others contained air-dried ground white locoweed. During the pre-treatment (days 1 to 5) and the post-treatment phases (days 11 to 15) non-social trials were conducted in which the feeding behavior of individual animals was investigated in an 80 m² arena containing 12 feeding bowls. During the treatment phase (days 6 to 10) social learning trials were conducted in which LA + LE pairs from the social interference group were exposed to 12 bowls of food distributed in an 80 m² arena intended to induce social interference, and LA + LE pairs from the social facilitation group were exposed to 36 bowls of food distributed in a 240 m² arena intended to permit social facilitation. During pre-treatment phase, LA heifers consumed detectably less locoweed and wheat straw and exhibited lower preference for locoweed than LE (P ⩽ 0.05) although wheat straw preference of LA and LE was similar. During social learning trials (treatment phase), LA in the social interference group visited similar number of locoweed bowls (mean ± s.e.m.: 0.2 ± 0.12) as they had during non-social learning (0.2 ± 0.20). Conversely, LA heifers in the social facilitation group visited detectably more locoweed bowls during social learning trials (1.6 ± 0.46) compared with the pre-treatment phase (0.2 ± 0.16). Correlation between daily number of locoweed bowls visited by LA and LE during social learning trials was detected in the social facilitation (r = 0.70; P < 0.01), but not in the social interference group (r = 0.15; P = 0.52). During testing trials (post-treatment phase), locoweed and wheat straw intake and preference of LA and LE in both treatment groups was similar. Manipulation of the feeding environment delayed, but did not inhibit social learning of toxic weed ingestion in this study.