Mate-guarding constrains feeding activity but not energetic status of wild male long-tailed macaques (Macaca fascicularis).

Mate-guarding is an important determinant of male reproductive success in a number of species. Little is known however about the constraints of this behaviour, e.g. the associated energetic costs. We investigated these costs in long-tailed macaques where alpha males mate guard females to a lesser extent than predicted by the priority of access model. The study was carried out during two mating periods on three wild groups living in the Gunung Leuser National Park, Indonesia. We combined behavioural observations on males' locomotion and feeding activity, GPS records of distance travelled and non-invasive measurements of urinary C-peptide (UCP), a physiological indicator of male energetic status. Mate-guarding led to a decrease in feeding time and fruit consumption suggesting a reduced intake of energy. At the same time, vertical locomotion was reduced, which potentially saved energy. These findings, together with the fact that we did not find an effect of mate-guarding on UCP levels, suggest that energy intake and expenditure was balanced during mate-guarding in our study males. Mate-guarding thus seems to not be energetically costly under all circumstances. Given that in strictly seasonal rhesus macaques, high-ranking males lose physical condition over the mating period, we hypothesise that the energetic costs of mate-guarding vary inter-specifically depending on the degree of seasonality and that males of non-strictly seasonal species might be better adapted to maintain balanced energetic condition year-round. Finally, our results illustrate the importance of combining behavioural assessments of both energy intake and expenditure with physiological measures when investigating energetic costs of behavioural strategies

Heparan sulfate proteoglycans: structure, protein interactions and cell signaling

Heparan sulfate proteoglycans are ubiquitously found at the cell surface and extracellular matrix in all the animal species. This review will focus on the structural characteristics of the heparan sulfate proteoglycans related to protein interactions leading to cell signaling. The heparan sulfate chains due to their vast structural diversity are able to bind and interact with a wide variety of proteins, such as growth factors, chemokines, morphogens, extracellular matrix components, enzymes, among others. There is a specificity directing the interactions of heparan sulfates and target proteins, regarding both the fine structure of the polysaccharide chain as well precise protein motifs. Heparan sulfates play a role in cellular signaling either as receptor or co-receptor for different ligands, and the activation of downstream pathways is related to phosphorylation of different cytosolic proteins either directly or involving cytoskeleton interactions leading to gene regulation. The role of the heparan sulfate proteoglycans in cellular signaling and endocytic uptake pathways is also discussed.Proteoglicanos de heparam sulfato são encontrados tanto superfície celular quanto na matriz extracelular em todas as espécies animais. Esta revisão tem enfoque nas características estruturais dos proteoglicanos de heparam sulfato e nas interações destes proteoglicanos com proteínas que levam à sinalização celular. As cadeias de heparam sulfato, devido a sua variedade estrutural, são capazes de se ligar e interagir com ampla gama de proteínas, como fatores de crescimento, quimiocinas, morfógenos, componentes da matriz extracelular, enzimas, entreoutros. Existe uma especificidade estrutural que direciona as interações dos heparam sulfatos e proteínas alvo. Esta especificidade está relacionada com a estrutura da cadeia do polissacarídeo e os motivos conservados da cadeia polipeptídica das proteínas envolvidas nesta interação. Os heparam sulfatos possuem papel na sinalização celular como receptores ou coreceptores para diferentes ligantes. Esta ligação dispara vias de sinalização celular levam à fosforilação de diversas proteínas citosólicas ou com ou sem interações diretas com o citoesqueleto, culminando na regulação gênica. O papel dos proteoglicanos de heparam sulfato na sinalização celular e vias de captação endocítica também são discutidas nesta revisão.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Departamento de BioquímicaUniversidade Federal de São Paulo (UNIFESP) Departamento de OftalmologiaUNIFESP, Depto. de BioquímicaUNIFESP, Depto. de OftalmologiaSciEL

Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life.

BACKGROUND: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life. METHODS: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed. RESULTS: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life. CONCLUSIONS: These findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life

Cost-effectiveness of a structured progressive task-oriented circuit class training programme to enhance walking competency after stroke: The protocol of the FIT-Stroke trial

<p>Abstract</p> <p>Background</p> <p>Most patients who suffer a stroke experience reduced walking competency and health-related quality of life (HRQoL). A key factor in effective stroke rehabilitation is intensive, task-specific training. Recent studies suggest that intensive, patient-tailored training can be organized as a circuit with a series of task-oriented workstations.</p> <p>Primary aim of the FIT-Stroke trial is to evaluate the effects and cost-effectiveness of a structured, progressive task-oriented circuit class training (CCT) programme, compared to usual physiotherapeutic care during outpatient rehabilitation in a rehabilitation centre. The task-oriented CCT will be applied in groups of 4 to 6 patients. Outcome will be defined in terms of gait and gait-related ADLs after stroke. The trial will also investigate the generalizability of treatment effects of task-oriented CCT in terms of perceived fatigue, anxiety, depression and perceived HRQoL.</p> <p>Methods/design</p> <p>The multicentre single-blinded randomized trial will include 220 stroke patients discharged to the community from inpatient rehabilitation, who are able to communicate and walk at least 10 m without physical, hands-on assistance. After discharge from inpatient rehabilitation, patients in the experimental group will receive task-oriented CCT two times a week for 12 weeks at the physiotherapy department of the rehabilitation centre. Control group patients will receive usual individual, face-to-face, physiotherapy. Costs will be evaluated by having each patient keep a cost diary for the first 24 weeks after randomisation. Primary outcomes are the mobility part of the Stroke Impact Scale (SIS-3.0) and the EuroQol. Secondary outcomes are the other domains of SIS-3.0, lower limb muscle strength, walking endurance, gait speed, balance, confidence not to fall, instrumental ADL, fatigue, anxiety, depression and HRQoL.</p> <p>Discussion</p> <p>Based on assumptions about the effect of intensity of practice and specificity of treatment effects, FIT-Stroke will address two key aims. The first aim is to investigate the effects of task-oriented CCT on walking competency and HRQoL compared to usual face-to-face physiotherapy. The second aim is to reveal the cost-effectiveness of task-oriented CCT in the first 6 months post stroke. Both aims were recently recommended as priorities by the American Hearth Association and Stroke Council.</p> <p>Trial registration</p> <p>This study is registered in the Dutch Trial Register as NTR1534.</p

Lessons Learned from Creating a Mobile Version of an Educational Board Game to Increase Situational Awareness

This paper reports on an iterative design process for a serious game, which aims to raise situational awareness among different stakeholders in a logistics value chain by introducing multi-user role-playing games. It does so in several phases: After introducing the field of logistics as a problem domain for an educational challenge, it firstly describes the design of an educational board game for the field of disruption handling in logistics processes. Secondly, it de-scribes how the board game can be realized in an open-source mobile serious games platform and identifies lessons learned based on advantages and issues found. Thirdly, it derives requirements for a re-design of the mobile game and finally draws conclusions.SALOM

Retromer and Its Role in Regulating Signaling at Endosomes.

The retromer complex is a key element of the endosomal protein sorting machinery being involved in trafficking of proteins from endosomes to the Golgi and also endosomes to the cell surface. There is now accumulating evidence that retromer also has a prominent role in regulating the activity of many diverse signaling proteins that traffic through endosomes and this activity has profound implications for the functioning of many different cell and tissue types from neuronal cells to cells of the immune system to specialized polarized epithelial cells of the retina. In this review, the protein composition of the retromer complex will be described along with many of the accessory factors that facilitate retromer-mediated endosomal protein sorting to detail how retromer activity contributes to the regulation of several distinct signaling pathways

SNX3 controls Wingless/Wnt secretion through regulating retromer-dependent recycling of Wntless

Drosophila Wingless (Wg) acts as a morphogen during development. Wg secretion is controlled by a seven-pass transmembrane cargo Wntless (Wls). We have recently identified retromer as a key regulator involved in Wls trafficking. As sorting nexin (SNX) molecules are essential components of the retromer complex, we hypothesized that specific SNX(s) is required for retromer-mediated Wnt secretion. Here, we generated Drosophila mutants for all of the eight snx members, and identified Drosophila SNX3 (DSNX3) as an essential molecule required for Wg secretion. We show that Wg secretion and its signaling activity are defective in Dsnx3 mutant clones in wing discs. Wg levels in the culture medium of Dsnx3-depleted S2 cells are also markedly reduced. Importantly, Wls levels are strikingly reduced in Dsnx3 mutant cells, and overexpression of Wls can rescue the Wg secretion defect observed in Dsnx3 mutant cells. Moreover, DSNX3 can interact with the retromer component Vps35, and co-localize with Vps35 in early endosomes. These data indicate that DSNX3 regulates Wg secretion via retromer-dependent Wls recycling. In contrast, we found that Wg secretion is not defective in cells mutant for Drosophila snx1 and snx6, two components of the classical retromer complex. Ectopic expression of DSNX1 or DSNX6 fails to rescue the Wg secretion defect in Dsnx3 mutant wing discs and in Dsnx3 dsRNA-treated S2 cells. These data demonstrate the specificity of the DSNX3-retromer complex in Wls recycling. Together, our findings suggest that DSNX3 acts as a cargo-specific component of retromer, which is required for endocytic recycling of Wls and Wg/Wnt secretion

A Visual Metaphor Describing Neural Dynamics in Schizophrenia

Background: In many scientific disciplines the use of a metaphor as an heuristic aid is not uncommon. A well known example in somatic medicine is the 'defense army metaphor' used to characterize the immune system. In fact, probably a large part of the everyday work of doctors consists of 'translating' scientific and clinical information (i.e. causes of disease, percentage of succes versus risk of side-effects) into information tailored to the needs and capacities of the individual patient. The ability to do so in an effective way is at least partly what makes a clinician a good communicator. Schizophrenia is a severe psychiatric disorder which affects approximately 1% of the population. Over the last two decades a large amount of molecular-biological, imaging and genetic data have been accumulated regarding the biological underpinnings of schizophrenia. However, it remains difficult to understand how the characteristic symptoms of schizophrenia such as hallucinations and delusions are related to disturbances on the molecular-biological level. In general, psychiatry seems to lack a conceptual framework with sufficient explanatory power to link the mental- and molecular-biological domains. Methodology/Principal Findings: Here, we present an essay-like study in which we propose to use visualized concepts stemming from the theory on dynamical complex systems as a 'visual metaphor' to bridge the mental- and molecular-biological domains in schizophrenia. We first describe a computer model of neural information processing; we show how the information processing in this model can be visualized, using concepts from the theory on complex systems. We then describe two computer models which have been used to investigate the primary theory on schizophrenia, the neurodevelopmental model, and show how disturbed information processing in these two computer models can be presented in terms of the visual metaphor previously described. Finally, we describe the effects of dopamine neuromodulation, of which disturbances have been frequently described in schizophrenia, in terms of the same visualized metaphor. Conclusions/Significance: The conceptual framework and metaphor described offers a heuristic tool to understand the relationship between the mental- and molecular-biological domains in an intuitive way. The concepts we present may serve to facilitate communicatio

Mating first, mating more: Biological market fluctuation in a wild prosimian

In biology, economics, and politics, distributive power is the key for understanding asymmetrical relationships and it can be obtained by force (dominance) or trading (leverage). Whenever males cannot use force, they largely depend on females for breeding opportunities and the balance of power tilts in favour of females. Thus, males are expected not only to compete within their sex-class but also to exchange services with the opposite sex. Does this mating market, described for humans and apes, apply also to prosimians, the most ancestral primate group? To answer the question, we studied a scent-oriented and gregarious lemur, Propithecus verreauxi (sifaka), showing female dominance, promiscuous mating, and seasonal breeding. We collected 57 copulations involving 8 males and 4 females in the wild (Berenty Reserve, South Madagascar), and data (all occurrences) on grooming, aggressions, and marking behaviour. We performed the analyses via exact Spearman and matrix correlations. Male mating priority rank correlated with the frequency of male countermarking over female scents but not with the proportion of fights won by males over females. Thus, males competed in an olfactory tournament more than in an arena of aggressive encounters. The copulation frequency correlated neither with the proportion of fights won by males nor with the frequency of male countermarking on female scents. Male-to-female grooming correlated with female-to-male grooming only during premating. Instead, in the mating period male-to-female grooming correlated with the copulation frequency. In short, the biological market underwent seasonal fluctuations, since males bargained grooming for sex in the mating days and grooming for itself in the premating period. Top scent-releasers gained mating priority (they mated first) and top groomers ensured a higher number of renewed copulations (they mated more). In conclusion, males maximize their reproduction probability by adopting a double tactic and by following marketfluctuations