The Effect of Brief or Prolonged Bouts of Winning or Losing Male-Male Contests on Plasticity in Sexually Selected Traits.

AbstractFight outcomes often affect male fitness by determining their access to mates. Thus, "winner-loser" effects, where winners often win their next contest while losers tend to lose, can influence how males allocate resources toward pre- and postcopulatory traits. We experimentally manipulated the winning/losing experiences of pairs of size-matched male Gambusia holbrooki for 1 day, 1 week, or 3 weeks to test whether prior winning/losing experiences differentially affect the plasticity of male investment into either mating effort (precopulatory) or ejaculates (postcopulatory). When winner/loser pairs directly competed for a female, winners had better precopulatory outcomes than losers for three of the four traits we measured: mating attempts, successful attempts, and time spent with the female (but not aggression). However, winners and losers did not differ in either total sperm counts or sperm velocity. Interestingly, absolute male size, an important predictor of fighting success, mediated winner-loser effects on how long males then spent near a female. Compared with losers, smaller winners spent more time with the female than did larger winners, suggesting that how males respond to prior social experiences is size dependent. We discuss the general importance of controlling for inherent male condition when comparing male investment into condition-dependent traits.

A meta-analysis of sex differences in animal personality: no evidence for the greater male variability hypothesis.

The notion that men are more variable than women has become embedded into scientific thinking. For mental traits like personality, greater male variability has been partly attributed to biology, underpinned by claims that there is generally greater variation among males than females in non-human animals due to stronger sexual selection on males. However, evidence for greater male variability is limited to morphological traits, and there is little information regarding sex differences in personality-like behaviours for non-human animals. Here, we meta-analysed sex differences in means and variances for over 2100 effects (204 studies) from 220 species (covering five broad taxonomic groups) across five personality traits: boldness, aggression, activity, sociality and exploration. We also tested if sexual size dimorphism, a proxy for sex-specific sexual selection, explains variation in the magnitude of sex differences in personality. We found no significant differences in personality between the sexes. In addition, sexual size dimorphism did not explain variation in the magnitude of the observed sex differences in the mean or variance in personality for any taxonomic group. In sum, we find no evidence for widespread sex differences in variability in non-human animal personality.

Does the winner-loser effect determine male mating success?

Winning or losing a fight can have lasting effects on competitors. Controlling for inherent fighting ability and other factors, a history of winning often makes individuals more likely to win future contests, while the opposite is true for losers (the 'winner-loser effect'). But does the winner-loser effect also influence a male's mating success? We experimentally staged contests between male mosquitofish (Gambusia holbrooki) such that focal males either won or lost three successive encounters with stimulus males. We then placed a size-matched (to control for inherent fighting ability) winner and loser with a female and monitored their behaviour (n = 63 trios). Winners spent significantly more time associating with the female. Winners did not make more copulation attempts, nor have a greater number of successful attempts. There was, however, a significant effect of male size on the number of successful copulation attempts: success decreased with male size for losers, but size had no effect on the success rate of winners.

Stage-Specific MicroRNAs and Their Role in the Anticancer Effects of Calorie Restriction in a Rat Model of ER-Positive Luminal Breast Cancer.

MicroRNAs have emerged as ubiquitous post-transcriptional regulators that coordinate many fundamental processes within cells, including those commonly linked to cancer when dysregulated. Profiling microRNAs across stages of cancer progression provides focus as to which microRNAs are key players in cancer development and are therefore important to manipulate with interventions to delay cancer onset and progression. Calorie restriction is one of the most effective preventive interventions across many types of cancer, although its effects on microRNAs have not been well characterized. We used the dimethylbenz[a]-anthracene-induced model of luminal mammary cancer in Sprague Dawley rats to elucidate which microRNAs are linked to progression in this type of cancer and, subsequently, to study how calorie restriction affects such microRNAs. We identified eight microRNAs (miR-10a, miR-10b, miR-21, miR-124, miR-125b, miR-126, miR-145 and miR-200a) to be associated with DMBA-induced mammary tumor progression. Calorie restriction, which greatly increased tumor-free survival and decreased the overall size of tumors that did develop, significantly decreased the expression of one microRNA, miR-200a, which was positively associated with tumor progression. We further showed that inhibition of miR-200a function, mimicking the effect of calorie restriction on this microRNA, inhibited proliferation in both rat (LA7) and human (MCF7) luminal mammary cancer cell lines. These findings present, for the first time, a stage-specific profile of microRNAs in a rodent model of luminal mammary cancer. Furthermore, we have identified the regulation of miR-200a, a microRNA that is positively associated with progression in this model, as a possible mechanism contributing to the anticancer effects of calorie restriction.

Calorie restriction decreases murine and human pancreatic tumor cell growth, nuclear factor-κB activation, and inflammation-related gene expression in an insulin-like growth factor-1-dependent manner.

Calorie restriction (CR) prevents obesity and has potent anticancer effects that may be mediated through its ability to reduce serum growth and inflammatory factors, particularly insulin-like growth factor (IGF)-1 and protumorigenic cytokines. IGF-1 is a nutrient-responsive growth factor that activates the inflammatory regulator nuclear factor (NF)-κB, which is linked to many types of cancers, including pancreatic cancer. We hypothesized that CR would inhibit pancreatic tumor growth through modulation of IGF-1-stimulated NF-κB activation and protumorigenic gene expression. To test this, 30 male C57BL/6 mice were randomized to either a control diet consumed ad libitum or a 30% CR diet administered in daily aliquots for 21 weeks, then were subcutaneously injected with syngeneic mouse pancreatic cancer cells (Panc02) and tumor growth was monitored for 5 weeks. Relative to controls, CR mice weighed less and had decreased serum IGF-1 levels and smaller tumors. Also, CR tumors demonstrated a 70% decrease in the expression of genes encoding the pro-inflammatory factors S100a9 and F4/80, and a 56% decrease in the macrophage chemoattractant, Ccl2. Similar CR effects on tumor growth and NF-κB-related gene expression were observed in a separate study of transplanted MiaPaCa-2 human pancreatic tumor cell growth in nude mice. In vitro analyses in Panc02 cells showed that IGF-1 treatment promoted NF-κB nuclear localization, increased DNA-binding of p65 and transcriptional activation, and increased expression of NF-κB downstream genes. Finally, the IGF-1-induced increase in expression of genes downstream of NF-κB (Ccdn1, Vegf, Birc5, and Ptgs2) was decreased significantly in the context of silenced p65. These findings suggest that the inhibitory effects of CR on Panc02 pancreatic tumor growth are associated with reduced IGF-1-dependent NF-κB activation.

Dietary energy balance modulation of Kras- and Ink4a/Arf+/--driven pancreatic cancer: the role of insulin-like growth factor-I.

New molecular targets and intervention strategies for breaking the obesity-pancreatic cancer link are urgently needed. Using relevant spontaneous and orthotopically transplanted murine models of pancreatic cancer, we tested the hypothesis that dietary energy balance modulation impacts pancreatic cancer development and progression through an insulin-like growth factor (IGF)-I-dependent mechanism. In LSL-Kras(G12D)/Pdx-1-Cre/Ink4a/Arf(lox/+) mice, calorie restriction versus overweight- or obesity-inducing diet regimens decreased serum IGF-I, tumoral Akt/mTOR signaling, pancreatic desmoplasia, and progression to pancreatic ductal adenocarcinoma (PDAC), and increased pancreatic tumor-free survival. Serum IGF-I, Akt/mTOR signaling, and orthotopically transplanted PDAC growth were decreased in liver-specific IGF-I-deficient mice (vs. wild-type mice), and rescued with IGF-I infusion. Thus, dietary energy balance modulation impacts spontaneous pancreatic tumorigenesis induced by mutant Kras and Ink4a deficiency, the most common genetic alterations in human pancreatic cancer. Furthermore, IGF-I and components of its downstream signaling pathway are promising mechanistic targets for breaking the obesity-pancreatic cancer link.