Intergroup Interactions in Crested Macaques (Macaca nigra): Factors Affecting Intergroup Encounter Outcome and Intensity

Between-group contest competition for access to resources and mates is widespread among social animals. These interactions can impact individual fitness influencing chances of survival and inter-birth interval lengths. Fitness benefits derived from intergroup contest competition are reaped by groups able to displace their opponents. Long and aggressive contests are costlier in terms of fitness than short and peaceful interactions. Therefore, net benefits from intergroup contests can depend on contest escalation. Factors affecting intergroup encounter outcomes and intensity may have an effect on individual fitness. However, we know relatively little about these factors. The aim of this thesis was to investigate what factors affect outcomes and intensity of intergroup encounters in crested macaques (Macaca nigra). Crested macaques have frequent between-group interactions, which makes of them a suitable model species to investigate this topic. My team and I collected data on 163 intergroup encounters between three neighbouring groups of habituated crested macaques in Tangkoko Nature Reserve (North Sulawesi, Indonesia) between November 2015 and July 2016. We also collected data on demography and use of space of these three groups. In my first study, I investigated whether between-group differences in group size and location-based payoffs could be used to infer the probability of intergroup encounter outcomes and intensity. Likelihood of draw and contact aggression were higher when group sizes were similar. Probability of winning an encounter was higher for groups bigger than their opponent and with higher location-based payoffs. Groups with higher location-based payoffs were able to displace groups bigger than themselves. In my second study, I explored whether models accounting for female and male reproductive strategies could be used to infer the probability of intergroup encounter outcome and intensity. I also assessed whether these models fitted the data better than those of the first study. Female and male reproductive strategies played important roles in determining outcome and intensity of intergroup encounters. I found evidence of female resource defence and male mate access defence via intergroup aggression and intragroup sexual coercion. Overall, accounting for reproductive strategies improved model fit. In my third study, I reported several cases of coalitionary attacks against members of other groups. These attacks resulted in injuries, loss of infants and death for the victims. The aggressions resembled, in several key aspects, intergroup coalitionary aggressions described in chimpanzee and human raids. Intergroup coalitionary attacks in crested macaques may improve the chances of the attacking groups to displace the victims’ groups in future encounters. My thesis provides the first in depth investigation on factors affecting outcome and intensity of intergroup encounters in crested macaques. These data might be useful in comparative studies on how intergroup relationships vary depending on socioecological factors such as resource abundance and social structure. This is also the first report pf repeated intergroup coalitionary aggressions with severe consequences for the victims in an Old World Monkey (Cercopithecidae) species. My findings highlight the role of reproductive strategies in intergroup encounter outcome and intensity and the need to consider female and male strategies together when investigating between-group contests

Cancer-associated fibroblasts in radiotherapy: Bystanders or protagonists?

Background - The primary goal of radiotherapy (RT) is to induce cellular damage on malignant cells; however, it is becoming increasingly recognized the important role played by the tumor microenvironment (TME) in therapy outcomes. Therapeutic irradiation of tumor lesions provokes profound cellular and biological reconfigurations within the TME that ultimately may influence the fate of the therapy. Main content - Cancer-associated fibroblasts (CAFs) are known to participate in all stages of cancer progression and are increasingly acknowledged to contribute to therapy resistance. Accumulated evidence suggests that, upon radiation, fibroblasts/CAFs avoid cell death but instead enter a permanent senescent state, which in turn may influence the behavior of tumor cells and other components of the TME. Despite the proposed participation of senescent fibroblasts on tumor radioprotection, it is still incompletely understood the impact that RT has on CAFs and the ultimate role that irradiated CAFs have on therapy outcomes. Some of the current controversies may emerge from generalizing observations obtained using normal fibroblasts and CAFs, which are different cell entities that may respond differently to radiation exposure. Conclusion - In this review we present current knowledge on the field of CAFs role in radiotherapy; we discuss the potential tumorigenic functions of radiation-induced senescent fibroblasts and CAFs and we make an effort to integrate the knowledge emerging from preclinical experimentation with observations from the clinics

A Universal Formulation for Multilevel Selective Harmonic Elimination - PWM with Half-Wave Symmetry

Selective harmonic elimination - pulse width modulation (SHE-PWM) can be utilized to improve the efficiency of multilevel voltage source converters due to its ability to provide low switching frequency and tight control of low-order harmonics. In addition, SHE-PWM with half-wave (HW) symmetry provides a higher number of solutions than quarter-wave (QW) symmetry and therefore, the waveform design can be improved. This work proposes a universal formulation, which can be utilized with HW symmetry, that provides a unique system of equations valid for any possible multilevel waveform. Thereby, without using predefined waveforms, this formulation provides the ability to search simultaneously both the firing angles and the switching patterns, simplifying significantly the search process and providing a high number of solutions. With the aim of selecting the optimum sets of firing angles, the solutions provided by HW and QW symmetries are compared, based on several metrics of harmonic performance, for particular test cases. Experimental results also validate the universal formulation with HW symmetry.Eusko Jaurlaritza; Secretaria de Estado de Investigacion Desarrollo e Innovacio

The Boomerang Effect: How Nurses' Regulation of Patients' Affect Associates With Their Own Emotional Exhaustion and Affective Experiences

Recent research has shown that the intentional regulation of others’ affect has effects not only on the target (e.g., a patient) of the regulation, but also on the agent (e.g., a nurse). In particular, the use of intentional interpersonal affect regulation strategies has been found to predict employees’ emotional exhaustion (EEx). Use of affect-worsening strategies is associated with an increase in EEx, whereas the effect of using affect-improving strategies is less clear. Another relevant consequence of interpersonal affect regulation is its effect on affective experiences, which is one of the main determinants of job attitudes. This study tests the relationships between the interpersonal affect regulation strategies that nurses use to regulate their patients’ affect and the nurses’ EEx and affective experiences. A longitudinal 2-wave field study was conducted in sample of nurses. Participants completed a questionnaire on 2 different occasions, 2 months apart (Time 1 [T1], Time 2 [T2]). Of the 141 participants at T1, 103 also completed the survey at T2. Longitudinal hierarchical regression analyses showed that using affect-worsening strategies was a significant predictor of nurse’s EEx, whereas using affect-improving strategies did not significantly predict their EEx. For affective experiences, use of affect-worsening strategies was related to nurses experiencing low-activation negative affect (e.g., feeling depressed); whereas affect-improving strategies was related to them experiencing low-activation positive affect (e.g., feeling calm). Results support the view that intentional regulation of patients’ affect needs to be considered not only in relation to the patients’ perception of service quality but also from the perspective of nurses’ well-being

Designing a generalised reward for Building Energy Management Reinforcement Learning agents

The reduction of the carbon footprint of buildings is a challenging task, partly due to the conflicting goals of maximising occupant comfort and minimising energy consumption. An intelligent management of Heating, Ventilation and Air Conditioning (HVAC) systems is creating a promising research line in which the creation of suitable algorithms could reduce energy consumption maintaining occupants' comfort. In this regard, Reinforcement Learning (RL) approaches are giving a good balance between data requirements and intelligent operations to control building systems. However, there is a gap concerning how to create a generalised reward signal that can train RL agents without delimiting the problem to a specific or controlled scenario. To tackle it, an analysis and discussion is presented about the necessary requirements for the creation of generalist rewards, with the objective of laying the foundations that allow the creation of generalist intelligent agents for building energy management.The work described in this paper was partially supported by the Basque Government under ELKARTEK project (LANTEGI4.0 KK-2020/00072)

Dynamic expression of VDR and 1-­alpha-­hydroxylase in differentiated and re-­differentiated human articular chondrocytes

Abstract of a presentation at a conference of the International Cartilage Repair Society.Purpose: The goal was to investigate potential roles played by vitamin D in the regulation of joint cartilage biology. We studied the expression of two central elements of vitamin D metabolism, namely the vitamin D receptor and its converting enzyme 1­α­hydroxylase in human knee cartilage and chondrocytes. Methods and Materials: Expression of receptor and enzyme was determined by immunohistochemistry/immunofluorescence, reversetranscriptase PCR and western blot on differentiated, de­differentiated and re­differentiated chondrocytes. Cartilage was harvested from a macroscopically healthy looking area of the lateral femoral condyle during knee replacement surgery in 4 otherwise healthy patients aged 50­70. Suspension cultures of differentiated chondrocytes were established by short enzymatic digestion of cartilage using Collagenase XI and further incubation in non­adherent vessels. De­differentiated cells were the result of serial expansion of chondrocytes during 4 weeks after isolation in monolayers cultures. Chondrocyte re­differentiation was achieved by propagating cell pellets for 3 weeks in the presence of chondro­inductive morphogens. Results: Both protein and gene expression of vitamin D receptor appear to be very low or undetectable in native cartilage and/or differentiated chondrocytes. In contrast, receptor expression was upregulated in dedifferentiated cells after monolayer expansion, however, this upregulation was lost when cells regained chondrogenic phenotype in 3D pellets. The expression of 1­α­hydroxylase was observed on the superficial layer of chondrocytes in native cartilage, which correlated with weak but detectable outcomes by PCR and western blot on differentiated cultures. Similarly, levels of the enzyme were increased after cell expansion in monolayers and decreased in 3D pellet cultures. Conclusion: Our study uncover a previously unknown regulation of vitamin D receptor between differentiated and redifferentiated phenotypes in cartilage cells. Furthermore, this study is pioneering on investigating the expression of 1­α­hydroxylase in cartilage tissue and chondrocytes. Further work is needed to ascertain if receptor and enzyme expression is regulated in disease conditions or affected by inflammatory environments

The effect of group size and individual characteristics on between-group encounters in primates

Between-group encounters are common in non-human primates and can vary from affiliative to aggressive. We extracted data from the literature to test five different hypotheses: 1) where there are group size differences between opposing groups, whether the larger group is more likely to win a between-group encounter than the smaller group; 2) whether the likelihood of a group engaging in aggressive between-group encounters increases with group size; and 3-5) whether dominant, older animals, and/or males are more likely to participate aggressively in between-group encounters than subordinate, younger animals and/or females. Our dataset comprised 52 studies on 31 primate species (3 lemur species, 5 New World monkeys, 19 Old World monkeys and 4 apes). We found that the larger group is more likely to win an encounter against a smaller group than vice-versa. We found no significant relationship between group size and propensity to be aggressive during between-group encounters. We found weak/no support for the effect of age, dominance rank and sex on the frequency of aggression displayed towards outgroup animals during between-group encounters. Species- and population-specific differences in between- and within-group competition and in the degree of the unequal distribution of resources across group members may explain why age, dominance rank and sex are not strong predictors of aggression during between-group encounters

Secretion rates and protein composition of extracellular vesicles released by cancer-associated fibroblasts after radiation

Reciprocal communication between the malignant and non-malignant cellular elements in tumors is essential for cancer sustainability and plays an important role in the response of cancers to treatments. Some of this cellular crosstalk takes place via secretion of vesicles that are actively released into the extracellular space by most cell types in tumors. Recent studies have demonstrated radiation-induced changes in the secretion rate and composition of extracellular vesicles (EVs), with impact on radiation-related cellular communication. However, little is known about the effects of different radiation regimens on the release of EVs by cells of the tumor microenvironment. In this study, we provide a comprehensive molecular characterization of EVs released by cultured primary lung tumor fibroblasts. We explore the quantitative and morphological changes triggered by ionizing radiation (IR), delivered as a single dose of 18 Gy or three consecutive daily medium-doses of 6 Gy. Cancer-associated fibroblasts (CAFs) secrete EVs with sizes ranging from 80 to 200 nm, expressing some of the classical exosome markers. Exposing CAFs to a single-high radiation dose (1 × 18 Gy) or fractionated medium-dose did not alter the release of CAF-EVs. The protein composition of CAF-EVs was analyzed by LC-MS/MS proteomics and revealed that CAF-EVs are enriched with heat shock proteins, integrins, tetraspanins, proteinases, collagens, growth factors and an array of molecules involved in the regulation of cell migration and the immune system. Quantitative proteomic analyses revealed minor changes in the protein composition of CAF-EVs after radiation exposure. Taken together, this study presents original data on lung tumor CAF-EV composition and reveals that release and protein cargo of CAF-EVs are largely unaltered after exposing CAFs to IR

Immunobiology of cancer-associated fibroblasts in the context of radiotherapy

Radiotherapy (RT) still represents a mainstay of treatment in clinical oncology. Traditionally, the effectiveness of radiotherapy has been attributed to the killing potential of ionizing radiation (IR) over malignant cells, however, it has become clear that therapeutic efficacy of RT also involves activation of innate and adaptive anti-tumor immune responses. Therapeutic irradiation of the tumor microenvironment (TME) provokes profound cellular and biological reconfigurations which ultimately may influence immune recognition. As one of the major constituents of the TME, cancer-associated fibroblasts (CAFs) play central roles in cancer development at all stages and are recognized contributors of tumor immune evasion. While some studies argue that RT affects CAFs negatively through growth arrest and impaired motility, others claim that exposure of fibroblasts to RT promotes their conversion into a more activated phenotype. Nevertheless, despite the well-described immunoregulatory functions assigned to CAFs, little is known about the interplay between CAFs and immune cells in the context of RT. In this review, we go over current literature on the effects of radiation on CAFs and the influence that CAFs have on radiotherapy outcomes, and we summarize present knowledge on the transformed cellular crosstalk between CAFs and immune cells after radiation

Expression and function of Leukotriene B4 receptors in human articular chondrocytes

Leukotriene B4 (LTB4) is linked to osteoarthritis (OA) development however the expression of LTB4 receptors in cartilage cells and the physiological effects of LTB4 on cartilage tissue remain unknown. In this study we find that human articular chondrocytes express LTB4 receptors and that these receptors are functional, however, LTB4 does not seem to affect importantly some primary chondrocyte functions