Depression-like behavior is dependent on age in male SAMP8 mice

Aging is associated with an increased risk of depression in humans. To elucidate the underlying mechanisms of depression and its dependence on aging, here we study signs of depression in male SAMP8 mice. For this purpose, we used the forced swimming test (FST). The total floating time in the FST was greater in SAMP8 than in SAMR1 mice at 9 months of age; however, this difference was not observed in 12-month-old mice, when both strains are considered elderly. Of the two strains, only the SAMP8 animals responded to imipramine treatment. We also applied the dexamethasone suppression test (DST) and studied changes in the dopamine and serotonin (5-HT) uptake systems, the 5-HT2a/2c receptor density in the cortex, and levels of TPH2. The DST showed a significant difference between SAMR1 and SAMP8 mice at old age. SAMP8 exhibits an increase in 5-HT transporter density, with slight changes in 5-HT2a/2c receptor density. In conclusion, SAMP8 mice presented depression-like behavior that is dependent on senescence process, because it differs from SAMR1, senescence resistant strain.

Effect of an 8-weeks aerobic training program in elderly on oxidative stress and HSP72 expression in leukocytes during antioxidant supplementation.

OBJECTIVE: To investigate the effect of aerobic training in the context of antioxidant supplementation on systemic oxidative stress and leukocytes heat shock protein (Hsp)72 expression in the elderly. DESIGN: Sixteen septuagenarians (8 males and 8 females, mean age 74.6) were supplemented with Vitamin C and E (respectively 500 and 100mg per day) and randomly assigned either to sedentary (AS) or individualized aerobically trained (AT) group for 8 weeks. METHODS: Plasma Vitamin C and E concentrations and aerobic fitness, as well as resting and post graded exercise (GXT) Hsp72 expression in leukocytes, plasma levels of thiobarbituric acid reactive substances (TBARS) and advanced oxidation protein product (AOPP) were measured pre and post training / supplementation. RESULTS: At the end of the intervention, the two groups showed a significant increase in resting plasma vitamin C and E (approximately 50 and 20% increase respectively) and a significant decrease in both resting and post GXT plasma TBARS and AOPP (approximately 25 and 20% decrease respectively). These changes were of similar magnitude in the two groups. The reduced oxidative stress was concomitant with a 15% decreased expression of Hsp72 in monocytes and granulocytes in both groups. CONCLUSION: This study provides evidence that in elderly, increased concentration of antioxidant vitamins C and E is associated with a reduction in oxidative stress and leukocytes Hsp72. In this context, 8 weeks of aerobic training has no impact on oxidative stress or leukocytes Hsp72 expression in elderly people.

Increased male offspring's risk of metabolic-neuroendocrine dysfunction and overweight after fructose-rich diet intake by the lactating mother.

An adverse endogenous environment during early life predisposes the organism to develop metabolic disorders. We evaluated the impact of intake of an iso-caloric fructose rich diet (FRD) by lactating mothers (LM) on several metabolic functions of their male offspring. On postnatal d 1, ad libitum eating, lactating Sprague-Dawley rats received either 10% F (wt/vol; FRD-LM) or tap water (controls, CTR-LM) to drink throughout lactation. Weaned male offspring were fed ad libitum a normal diet, and body weight (BW) and food intake were registered until experimentation (60 d of age). Basal circulating levels of metabolic markers were evaluated. Both iv glucose tolerance and hypothalamic leptin sensitivity tests were performed. The hypothalamus was dissected for isolation of total RNA and Western blot analysis. Retroperitoneal (RP) adipose tissue was dissected and either kept frozen for gene analysis or digested to isolate adipocytes or for histological studies. FRD rats showed increased BW and decreased hypothalamic sensitivity to exogenous leptin, enhanced food intake (between 49-60 d), and decreased hypothalamic expression of several anorexigenic signals. FRD rats developed increased insulin and leptin peripheral levels and decreased adiponectinemia; although FRD rats normally tolerated glucose excess, it was associated with enhanced insulin secretion. FRD RP adipocytes were enlarged and spontaneously released high leptin, although they were less sensitive to insulin-induced leptin release. Accordingly, RP fat leptin gene expression was high in FRD rats. Excessive fructose consumption by lactating mothers resulted in deep neuroendocrine-metabolic disorders of their male offspring, probably enhancing the susceptibility to develop overweight/obesity during adult life.

Male mutation bias and possible long-term effects of human activities.

The ability of a population to adapt to changing environments depends critically on the amount and kind of genetic variability it possesses. Mutations are an important source of new genetic variability and may lead to new adaptations, especially if the population size is large. Mutation rates are extremely variable between and within species, and males usually have higher mutation rates as a result of elevated rates of male germ cell division. This male bias affects the overall mutation rate. We examined the factors that influence male mutation bias, and focused on the effects of classical life-history parameters, such as the average age at reproduction and elevated rates of sperm production in response to sexual selection and sperm competition. We argue that human-induced changes in age at reproduction or in sexual selection will affect male mutation biases and hence overall mutation rates. Depending on the effective population size, these changes are likely to influence the long-term persistence of a population.

Depression-like behavior is dependent on age in male SAMP8 mice

Aging is associated with an increased risk of depression in humans. To elucidate the underlying mechanisms of depression and its dependence on aging, here we study signs of depression in male SAMP8 mice. For this purpose, we used the forced swimming test (FST). The total floating time in the FST was greater in SAMP8 than in SAMR1 mice at 9 months of age; however, this difference was not observed in 12-month-old mice, when both strains are considered elderly. Of the two strains, only the SAMP8 animals responded to imipramine treatment. We also applied the dexamethasone suppression test (DST) and studied changes in the dopamine and serotonin (5-HT) uptake systems, the 5-HT2a/2c receptor density in the cortex, and levels of TPH2. The DST showed a significant difference between SAMR1 and SAMP8 mice at old age. SAMP8 exhibits an increase in 5-HT transporter density, with slight changes in 5-HT2a/2c receptor density. In conclusion, SAMP8 mice presented depression-like behavior that is dependent on senescence process, because it differs from SAMR1, senescence resistant strain.

Altered nitrogen balance and decreased urea excretion in male rats fed cafeteria diet are related to arginine availability

Hyperlipidic diets limit glucose oxidation and favor amino acid preservation, hampering the elimination of excess dietary nitrogen and the catabolic utilization of amino acids.We analyzed whether reduced urea excretion was a consequence of higherNO ; (nitrite,nitrate, and other derivatives) availability caused by increased nitric oxide production in metabolic syndrome. Rats fed a cafeteria diet for 30 days had a higher intake and accumulation of amino acid nitrogen and lower urea excretion.There were no differences in plasma nitrate or nitrite. NO and creatinine excretion accounted for only a small part of total nitrogen excretion. Rats fed a cafeteria diet had higher plasma levels of glutamine, serine, threonine, glycine, and ornithinewhen comparedwith controls,whereas arginine was lower. Liver carbamoyl-phosphate synthetase I activity was higher in cafeteria diet-fed rats, but arginase I was lower. The high carbamoyl-phosphate synthetase activity and ornithine levels suggest activation of the urea cycle in cafeteria diet-fed rats, but low arginine levels point to a block in the urea cycle between ornithine and arginine, thereby preventing the elimination of excess nitrogen as urea. The ultimate consequence of this paradoxical block in the urea cycle seems to be the limitation of arginine production and/or availability.

Mate availability and male dispersal in the Argentine ant Linepithema humile (Mayr) (=Iridomyrmex humilis)

In the Argentine ant Linepithema humile (=Iridomyrmex humilis) only males disperse whereas female sexuals (unmated winged queens) stay in their mother nest where they mate. This study investigated (1) whether dispersing males are accepted into foreign colonies, (2) whether they can mate with resident female sexuals, and (3) whether the propensity of males to disperse is affected by the expectation of mating in their mother nest. Field experiments demonstrated that males were accepted into foreign colonies only when these colonies contained female sexuals or queen pupae. Before and after the time of (sic) female sexuals, workers attacked and killed most of the foreign males. Laboratory experiments snowed that males that successfully enter foreign colonies can mate with resident female sexuals. The propensity of males to disperse was significantly influenced by the presence of female sexuals in their nest. Males were more likely to fly out from colonies containing no female sexuals than from those with them. These results are consistent with males preferentially dispersing when there is little or no opportunity to mate in their mother nest. Thus there are two mating strategies available for males: staying in their mother nest when an opportunity to mate arises or dispersing and attempting to mate in a foreign nest when there are no female sexuals in their mother nest. This latter behaviour could mediate gene flow between colonies and account for the lack of significant inbreeding previously documented in this species.

Prevalence of frailty in middle-aged and older community-dwelling Europeans living in 10 countries.

BACKGROUND: Frailty is an indicator of health status in old age. Its frequency has been described mainly for North America; comparable data from other countries are lacking. Here we report on the prevalence of frailty in 10 European countries included in a population-based survey. METHODS: Cross-sectional analysis of 18,227 randomly selected community-dwelling individuals 50 years of age and older, enrolled in the Survey of Health, Aging and Retirement in Europe (SHARE) in 2004. Complete data for assessing a frailty phenotype (exhaustion, shrinking, weakness, slowness, and low physical activity) were available for 16,584 participants. Prevalences of frailty and prefrailty were estimated for individuals 50-64 years and 65 years of age and older from each country. The latter group was analyzed further after excluding disabled individuals. We estimated country effects in this subset using multivariate logistic regression models, controlling first for age, gender, and then demographics and education. RESULTS: The proportion of frailty (three to five criteria) or prefrailty (one to two criteria) was higher in southern than in northern Europe. International differences in the prevalences of frailty and prefrailty for 65 years and older group persisted after excluding the disabled. Demographic characteristics did not account for international differences; however, education was associated with frailty. Controlling for education, age and gender diminished the effects of residing in Italy and Spain. CONCLUSIONS: A higher prevalence of frailty in southern countries is consistent with previous findings of a north-south gradient for other health indicators in SHARE. Our data suggest that socioeconomic factors like education contribute to these differences in frailty and prefrailty.

Genetic variability of rice recurrent selection populations as affected by male sterility or manual recombination

The objective of this work was to determine the effect of male sterility or manual recombination on genetic variability of rice recurrent selection populations. The populations CNA-IRAT 4, with a gene for male sterility, and CNA 12, which was manually recombined, were evaluated. Genetic variability among selection cycles was estimated using14 simple sequence repeat (SSR) markers. A total of 926 plants were analyzed, including ten genitors and 180 individuals from each of the evaluated cycles (1, 2 and 5) of the population CNA-IRAT 4, and 16 genitors and 180 individuals from each of the cycles (1 and 2) of CNA 12. The analysis allowed the identification of alleles not present among the genitors for both populations, in all cycles, especially for the CNA-IRAT 4 population. These alleles resulted from unwanted fertilization with genotypes that were not originally part of the populations. The parameters of Wright's F-statistic (F IS and F IT) indicated that the manual recombination expands the genetic variability of the CNA 12 population, whereas male sterility reduces the one of CNA-IRAT 4.

Instruments for investigating fitness to drive - needs and expectations in primary care: a qualitative study

Background: Primary care physicians are often requested to assess their patients' fitness to drive. Little is however known on their needs to help them in this task. Aims: The aim of this study is to develop theories on needs, expectations, and barriers for clinical instruments helping physicians assess fitness to drive in primary care. Methods: This qualitative study used semi-structured interviews to investigate needs and expectations for instruments used to assess fitness to drive. From August 2011 to April 2013, we recorded opinions from five experts in traffic medicine, five primary care physicians, and five senior drivers. All interviews were integrally transcribed. Two independent researchers extracted, coded, and stratified categories relying on multi-grounded theory. All participants validated the final scheme. Results: Our theory suggests that for an instruments assessing fitness to drive to be implemented in primary care, it need to contribute to the decisional process. This requires at least five conditions: 1) it needs to reduce the range of uncertainty, 2) it needs to be adapted to local resources and possibilities, 3) it needs to be accepted by patients, 4) choices of tasks need to adaptable to clinical conditions, 5) and interpretation of results need to remain dependant of each patient's context. Discussion and conclusions: Most existing instruments assessing fitness to drive are not designed for primary care settings. Future instruments should also aim to support patient-centred dialogue, help anticipate driving cessation, and offer patients the opportunity to freely take their own decision on driving cessation as often as possible.

Fitness to drive and cannabis: Experimental and real-life case study validation of two blood THCCOOH thresholds to distinguish occasional users from heavy smokers

Introduction: THC-COOH has been proposed as a criterion to help to distinguish between occasional from regular cannabis users. However, to date this indicator has not been adequately assessed under experimental and real-life conditions. Methods: We carried out a controlled administration study of smoked cannabis with a placebo. Twenty-three heavy smokers and 25 occasional smokers, between 18 and 30 years of age, participated in this study [Battistella G et al., PloS one. 2013;8(1):e52545]. We collected data from a second real case study performed with 146 traffic offenders' cases in which the whole blood cannabinoid concentrations and the frequency of cannabis use were known. Cannabinoid levels were determined in whole blood using tandem mass spectrometry methods. Results: Significantly high differences in THC-COOH concentrations were found between the two groups when measured during the screening visit, prior to the smoking session, and throughout the day of the experiment. Receiver operating characteristic (ROC) curves were determined and two threshold criteria were proposed in order to distinguish between these groups: a free THC-COOH concentration below 3 μg/L suggested an occasional consumption (≤ 1 joint/week) while a concentration higher than 40 μg/L corresponded to a heavy use (≥ 10 joints/month). These thresholds were successfully tested with the second real case study. The two thresholds were not challenged by the presence of ethanol (40% of cases) and of other therapeutic and illegal drugs (24%). These thresholds were also found to be consistent with previously published experimental data. Conclusion: We propose the following procedure that can be very useful in the Swiss context but also in other countries with similar traffic policies: If the whole blood THC-COOH concentration is higher than 40 μg/L, traffic offenders must be directed first and foremost toward medical assessment of their fitness to drive. This evaluation is not recommended if the THC-COOH concentration is lower than 3 μg/L. A THC-COOH level between these two thresholds can't be reliably interpreted. In such a case, further medical assessment and follow up of the fitness to drive are also suggested, but with lower priority.

Avian Evolutionary Genomics: Studies of Ficedula Flycatchers

In this thesis, different genetic tools are used to investigate both natural variation and speciation in the Ficedula flycatcher system: pied (Ficedula hypoleuca) and collared (F. albicollis) flycatchers. The molecular evolution of a gene involved in postnatal body growth, GH, has shown high degree of conservation at the mature protein between birds and mammals, whereas the variation observed in its signal peptide seems to be adaptive in pied flycatcher (I & II). Speciation is the process by which reproductive barriers to gene flow evolve between populations, and understanding the mechanisms involved in pre- and post-zygotic isolation have been investigated in Ficedula flycatchers. The Z chromosome have been suggested to be the hotspot for genes involved in speciation, thus sequencing of 13 Z-linked coding genes from the two species in allopatry and sympatry have been conducted (III). Surprisingly, the majority of Z-linked genes seemed to be highly conserved, suggesting instead a potential involvement of regulatory regions. Previous studies have shown that genes involved in hybrid fitness, female preferences and male plumage colouration are sex-linked. Hence, three pigmentation genes have been investigated: MC1R, AGRP, and TYRP1. Of these three genes, TYRP1 was identified as a strong candidate to be associated with black-brown plumage variation in sympatric populations, and hence is a strong candidate for a gene contributing to pre-zygotic isolation (IV). In sympatric areas, where pied and collared flycatchers have overlapping breeding areas, hybridization sometimes occurs leading to the production of unfit hybrids. By using a proteomic approach a novel expression pattern in hybrids was revealed compared to the parental species (V) and differentially expressed proteins subsequently identified by sequence similarity (VI). In conclusion, the Z chromosome appears to play an important role in flycatcher speciation, but probably not at the coding level. In addition the novel expression patterns might give new insights into the maladaptive hybrids.

Genetic components to caste allocation in a multiple-queen ant species.

Reproductive division of labor and the coexistence of distinct castes are hallmarks of insect societies. In social insect species with multiple queens per colony, the fitness of nestmate queens directly depends on the process of caste allocation (i.e., the relative investment in queen, sterile worker and male production). The aim of this study is to investigate the genetic components to the process of caste allocation in a multiple-queen ant species. We conducted controlled crosses in the Argentine ant Linepithema humile and established single-queen colonies to identify maternal and paternal family effects on the relative production of new queens, workers, and males. There were significant effects of parental genetic backgrounds on various aspects of caste allocation: the paternal lineage affected the proportion of queens and workers produced whereas the proportions of queens and males, and females and males were influenced by the interaction between parental lineages. In addition to revealing nonadditive genetic effects on female caste determination in a multiple-queen ant species, this study reveals strong genetic compatibility effects between parental genomes on caste allocation components.