Unraveling female communication through scent marks in the Norway rat.

Chemical communication by females remains poorly understood, with most attention focused on female advertisement of sexual receptivity to males or mother-offspring communication. However, in social species, scents are likely to be important for mediating competition and cooperation between females determining individual reproductive success. Here, we explore chemical signaling by female laboratory rats (Rattus norvegicus) to test i) whether females target their deployment of scent information differentially according to their sexual receptivity and the genetic identity of both female and male conspecifics signaling in the local environment and ii) whether females are attracted to gain the same or different information from female scents compared to males. Consistent with targeting of scent information to colony members of similar genetic background, female rats increased scent marking in response to scents from females of the same strain. Females also suppressed scent marking in response to male scent from a genetically foreign strain while sexually receptive. Proteomic analysis of female scent deposits revealed a complex protein profile, contributed from several sources but dominated by clitoral gland secretion. In particular, female scent marks contained a series of clitoral-derived hydrolases and proteolytically truncated major urinary proteins (MUPs). Manipulated blends of clitoral secretion and urine from estrus females were strongly attractive to both sexes, while voided urine alone stimulated no interest. Our study reveals that information about female receptive status is shared between females as well as with males, while clitoral secretions containing a complex set of truncated MUPs and other proteins play a key role in female communication.

Estimation of physical activity intensity cut-points using accelerometry in breast cancer survivors and age-matched controls.

OBJECTIVE: To examine the association between accelerometer activity counts and energy expenditure during walking in breast cancer survivors (BCS) compared with age-matched healthy controls, and differences in moderate-to-vigorous physical activity (MVPA) cut-points. METHODS: Using a case-control design, 19 BCS and 19 age-matched women completed 6 min of resting energy expenditure and 6-min periods of treadmill walking in Midwestern United States. Accelerometers and an open-circuit spirometry system were used to measure activity counts and energy expenditure (VO2 ). A mixed-factor analysis of variance was conducted on activity counts and VO2 . Independent samples t tests compared the magnitude of associations between groups. RESULTS: There were group by speed interactions on energy expenditure (p < 0.001) and counts (p < 0.001). The linear association did not differ between BCS and controls for the R2 (p = 0.62) nor the slope (p = 0.43), but there was a difference in the intercept (p = 0.01). This resulted in different MVPA cut-points between groups: 1,439 ± 761 counts·min-1 in BCS and 1,937 ± 639 counts·min-1 in controls. CONCLUSION: The findings support the use of different cut-points to quantify time spent in MVPA for BCS. Application of these cut-points is warranted to accurately assess physical activity (PA) patterns for better prescription and health outcomes in PA programmes for BCS.

Individual odour signatures that mice learn are shaped by involatile major urinary proteins (MUPs).

BACKGROUND: Reliable recognition of individuals requires phenotypic identity signatures that are both individually distinctive and appropriately stable over time. Individual-specific vocalisations or visual patterning are well documented among birds and some mammals, whilst odours play a key role in social recognition across many vertebrates and invertebrates. Less well understood, though, is whether individuals are recognised through variation in cues that arise incidentally from a wide variety of genetic and non-genetic differences between individuals, or whether animals evolve distinctive polymorphic signals to advertise identity reliably. As a bioassay to understand the derivation of individual-specific odour signatures, we use female attraction to the individual odours of male house mice (Mus musculus domesticus), learned on contact with a male's scent marks. RESULTS: Learned volatile odour signatures are determined predominantly by individual differences in involatile major urinary protein (MUP) signatures, a specialised set of communication proteins that mice secrete in their urine. Recognition of odour signatures in genetically distinct mice depended on differences in individual MUP genotype. Direct manipulation using recombinant MUPs confirmed predictable changes in volatile signature recognition according to the degree of matching between MUP profiles and the learned urine template. Both the relative amount of the male-specific MUP pheromone darcin, which induces odour learning, and other MUP isoforms influenced learned odour signatures. By contrast, odour recognition was not significantly influenced by individual major histocompatibility complex genotype. MUP profiles shape volatile odour signatures through isoform-specific differences in binding and release of urinary volatiles from scent deposits, such that volatile signatures were recognised from the urinary protein fraction alone. Manipulation using recombinant MUPs led to quantitative changes in the release of known MUP ligands from scent deposits, with MUP-specific and volatile-specific effects. CONCLUSIONS: Despite assumptions that many genes contribute to odours that can be used to recognise individuals, mice have evolved a polymorphic combinatorial MUP signature that shapes distinctive volatile signatures in their scent. Such specific signals may be more prevalent within complex body odours than previously realised, contributing to the evolution of phenotypic diversity within species. However, differences in selection may also result in species-specific constraints on the ability to recognise individuals through complex body scents.

Relationship between fruit and vegetable intake and interference control in breast cancer survivors.

PURPOSE: Nutrition plays an important role in brain structure and function, and the effects of diet may even be greater in those at greater risk of cognitive decline, such as individuals with cancer-related cognitive impairment. However, the relation of dietary components to cognitive function in cancer survivors is unknown. The objective of this study was to determine whether breast cancer survivors (BCS) evidenced impairments in interference control, a component of cognitive control, compared to age-matched women with no prior history of cancer, and to examine the moderating role of diet on cognitive function. METHODS: In this cross-sectional study, a modified flanker task was used to assess interference control in BCS (n = 31) and age-matched women with no prior history of cancer (n = 30). Diet was assessed with 3-day food records. Differences between BCS and age-matched controls were assessed using linear mixed models, and multilevel regression analyses were conducted to assess the moderating role of diet on cognitive performance. RESULTS: Cognitive performance was not different between groups. Fruit intake and vegetable intake were significantly associated with better performance on the incompatible condition of the flanker task (i.e., shorter reaction time and increased accuracy), independent of disease status. The association between dietary components and cognition was stronger for the incompatible incongruent condition, suggesting that fruit and vegetables may be important for the up-regulation of cognitive control when faced with higher cognitive demands. CONCLUSIONS: There was no difference in performance on an interference control task between BCS and age-matched controls. The data suggest that greater fruit intake and vegetable intake were positively associated with interference control in both BCS and age-matched controls.

Preliminary validation of the short physical performance battery in older adults with multiple sclerosis: secondary data analysis.

BACKGROUND: There are relatively few standard, objective measures for studying physical function among older adults with multiple sclerosis (MS), yet such measures are necessary considering the shift in prevalence and associated consequences of both MS and older age on physical function. We undertook a preliminary examination of the construct validity of Short Physical Performance Battery (SPPB) scores in older adults with MS based on an expected differential pattern of associations with measures of lower and upper extremity function. METHODS: The sample included 48 persons with MS aged 50 years and older who were enrolled in a pilot, randomized controlled trial of exercise training. Participants completed the SPPB and other objective and self-report measures of lower and upper extremity function as part of baseline testing. RESULTS: SPPB scores demonstrated strong associations with measures of lower extremity function (|r s| = .66-.79), and weak associations with measures of upper extremity function (|r s| = .03-.33). CONCLUSIONS: We provide preliminary evidence that supports the validity of scores from the SPPB as a measure of lower extremity function for inclusion in clinical research and practice involving older adults with MS.

Darcin: a male pheromone that stimulates female memory and sexual attraction to an individual male's odour.

BACKGROUND: Among invertebrates, specific pheromones elicit inherent (fixed) behavioural responses to coordinate social behaviours such as sexual recognition and attraction. By contrast, the much more complex social odours of mammals provide a broad range of information about the individual owner and stimulate individual-specific responses that are modulated by learning. How do mammals use such odours to coordinate important social interactions such as sexual attraction while allowing for individual-specific choice? We hypothesized that male mouse urine contains a specific pheromonal component that invokes inherent sexual attraction to the scent and which also stimulates female memory and conditions sexual attraction to the airborne odours of an individual scent owner associated with this pheromone. RESULTS: Using wild-stock house mice to ensure natural responses that generalize across individual genomes, we identify a single atypical male-specific major urinary protein (MUP) of mass 18893Da that invokes a female's inherent sexual attraction to male compared to female urinary scent. Attraction to this protein pheromone, which we named darcin, was as strong as the attraction to intact male urine. Importantly, contact with darcin also stimulated a strong learned attraction to the associated airborne urinary odour of an individual male, such that, subsequently, females were attracted to the airborne scent of that specific individual but not to that of other males. CONCLUSIONS: This involatile protein is a mammalian male sex pheromone that stimulates a flexible response to individual-specific odours through associative learning and memory, allowing female sexual attraction to be inherent but selective towards particular males. This 'darcin effect' offers a new system to investigate the neural basis of individual-specific memories in the brain and give new insights into the regulation of behaviour in complex social mammals.See associated Commentary http://www.biomedcentral.com/1741-7007/8/71.

Molecular complexity of the major urinary protein system of the Norway rat, Rattus norvegicus.

Major urinary proteins (MUP) are the major component of the urinary protein fraction in house mice (Mus spp.) and rats (Rattus spp.). The structure, polymorphism and functions of these lipocalins have been well described in the western European house mouse (Mus musculus domesticus), clarifying their role in semiochemical communication. The complexity of these roles in the mouse raises the question of similar functions in other rodents, including the Norway rat, Rattus norvegicus. Norway rats express MUPs in urine but information about specific MUP isoform sequences and functions is limited. In this study, we present a detailed molecular characterization of the MUP proteoforms expressed in the urine of two laboratory strains, Wistar Han and Brown Norway, and wild caught animals, using a combination of manual gene annotation, intact protein mass spectrometry and bottom-up mass spectrometry-based proteomic approaches. Cluster analysis shows the existence of only 10 predicted mup genes. Further, detailed sequencing of the urinary MUP isoforms reveals a less complex pattern of primary sequence polymorphism in the rat than the mouse. However, unlike the mouse, rat MUPs exhibit added complexity in the form of post-translational modifications, including the phosphorylation of Ser4 in some isoforms, and exoproteolytic trimming of specific isoforms. Our results raise the possibility that urinary MUPs may have different roles in rat chemical communication than those they play in the house mouse. Shotgun proteomics data are available via ProteomExchange with identifier PXD013986.

Molecular heterogeneity in major urinary proteins of Mus musculus subspecies: potential candidates involved in speciation.

When hybridisation carries a cost, natural selection is predicted to favour evolution of traits that allow assortative mating (reinforcement). Incipient speciation between the two European house mouse subspecies, Mus musculus domesticus and M.m.musculus, sharing a hybrid zone, provides an opportunity to understand evolution of assortative mating at a molecular level. Mouse urine odours allow subspecific mate discrimination, with assortative preferences evident in the hybrid zone but not in allopatry. Here we assess the potential of MUPs (major urinary proteins) as candidates for signal divergence by comparing MUP expression in urine samples from the Danish hybrid zone border (contact) and from allopatric populations. Mass spectrometric characterisation identified novel MUPs in both subspecies involving mostly new combinations of amino acid changes previously observed in M.m.domesticus. The subspecies expressed distinct MUP signatures, with most MUPs expressed by only one subspecies. Expression of at least eight MUPs showed significant subspecies divergence both in allopatry and contact zone. Another seven MUPs showed divergence in expression between the subspecies only in the contact zone, consistent with divergence by reinforcement. These proteins are candidates for the semiochemical barrier to hybridisation, providing an opportunity to characterise the nature and evolution of a putative species recognition signal.

Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors.

Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment.

Effects of a DVD-delivered exercise intervention on physical function in older adults with multiple sclerosis: A pilot randomized controlled trial.

BACKGROUND: Older adults with multiple sclerosis (MS) exhibit disease-related impairments such as compromised strength, balance, mobility, coordination, and quality of life (QOL). Exercise training as an intervention to reverse these conditions in older adults with MS is limited. OBJECTIVE: The objective of this pilot trial was to examine the effects of a DVD exercise intervention targeting flexibility, strength, and balance in older adults with MS in order to generate effect sizes to power a larger trial. METHODS: Participants were randomly assigned to a six-month DVD exercise intervention (n = 24) or a healthy aging DVD control condition (n = 24). Measures of physical function, physical activity, sedentary behavior, QOL and program satisfaction were assessed at baseline and at follow-up. RESULTS: The DVD exercise intervention was well received with no adverse events. Effects sizes ranged from small to modest reflecting improved function, increased physical activity, decreased sitting time, and improved QOL in the intervention condition compared to the control condition. CONCLUSION: This pilot randomized controlled trial suggests that older adults with MS are receptive to an exercise program via DVD, and the program results in modest but potentially important improvements in function and physical activity.

Improving physical functional and quality of life in older adults with multiple sclerosis via a DVD-delivered exercise intervention: a study protocol.

INTRODUCTION: There is a need to identify innovative, low-cost and broad-reaching strategies for promoting exercise and improving physical function in older adults with multiple sclerosis (MS). METHODS AND ANALYSIS: This randomised controlled pilot trial will test the efficacy of a 6-month, DVD-delivered exercise intervention to improve functional performance and quality of life in older adults with MS. Participants will be randomised either into a DVD-delivered exercise condition or an attentional control condition. This novel approach to programme delivery provides participants with detailed exercise instructions which are presented in a progressive manner and includes a variety of modifications to better meet varying levels of physical abilities. The targeted exercises focus on three critical elements of functional fitness: flexibility, strength and balance. It is hypothesised that participants who are randomised to the exercise DVD condition will demonstrate improvements in physical function compared with participants assigned to the attentional control condition. Data analysis will include a 2 (condition)×2 (time) mixed factor analysis of variance (ANOVA) that follows intent-to-treat principles, as well as an examination of effect sizes. Participants will take part in qualitative interviews about perspectives on physical activity and programme participation. ETHICS AND DISSEMINATION: The study protocol was approved by a university institutional review board and registered with a federal database. Participants will be asked to read and sign a detailed informed consent document and will be required to provide a physician's approval to participate in the study. The exercise DVDs include an overview of safety-related concerns and recommendations relative to exercise participation, as well as detailed instructions highlighting the proper execution of each exercise presented on screen. Following completion of this trial, data will be immediately analysed and results will be presented at scientific meetings and published in scholarly journals. TRIAL REGISTRATION NUMBER: Clinical Trials NCT01993095.

Pheromonal induction of spatial learning in mice.

Many mammals use scent marking for sexual and competitive advertisement, but little is known about the mechanism by which scents are used to locate mates and competitors. We show that darcin, an involatile protein sex pheromone in male mouse urine, can rapidly condition preference for its remembered location among females and competitor males so that animals prefer to spend time in the site even when scent is absent. Learned spatial preference is conditioned through contact with darcin in a single trial and remembered for approximately 14 days. This pheromone-induced learning allows animals to relocate sites of particular social relevance and provides proof that pheromones such as darcin can be highly potent stimuli for social learning.