Stranger to Familiar: Wild Strepsirhines Manage Xenophobia by Playing

The power of play in limiting xenophobia is a well-known phenomenon in humans. Yet, the evidence in social animals remains meager. Here, we aim to determine whether play promotes social tolerance toward strangers in one of the most basal group of primates, the strepsirhines. We observed two groups of wild lemurs (Propithecus verreauxi, Verreaux's sifaka) during the mating season. Data were also collected on nine visiting, outgroup males. We compared the distribution of play, grooming, and aggressive interactions across three conditions: OUT (resident/outgroup interactions), IN (resident/resident interactions in presence of outgroups) and BL-IN (baseline of resident/resident interactions in absence of outgroups). Play frequency between males was higher in OUT than in IN and BL-IN conditions; whereas, grooming was more frequent in IN than in OUT and BL-IN conditions. Aggression rates between resident and outgroup males were significantly higher than those between residents. However, aggressions between resident and outgroup males significantly decreased after the first play session and became comparable with resident-resident aggression levels. The presence of strangers in a well-established group implies the onset of novel social circumstances, which sifaka males cope with by two different tactics: grooming with ingroup males and playing with outgroup ones. The grooming peak, concurrently with the visit of outgroups, probably represents a social shield adopted by resident males to make their pre-existing affiliation more evident to the stranger “audience”. Being mostly restricted to unfamiliar males, adult play in sifaka appears to have a role in managing new social situations more than in maintaining old relationships. In particular, our results indicate not only that play is the interface between strangers but also that it has a specific function in reducing xenophobia. In conclusion, play appears to be an ice-breaker mechanism in the critical process that “upgrades” an individual from stranger to familiar

Sexual Signalling in Propithecus verreauxi: Male “Chest Badge” and Female Mate Choice

Communication, an essential prerequisite for sociality, involves the transmission of signals. A signal can be defined as any action or trait produced by one animal, the sender, that produces a change in the behaviour of another animal, the receiver. Secondary sexual signals are often used for mate choice because they may inform on a potential partner's quality. Verreaux's sifaka (Propithecus verreauxi) is characterized by the presence of two different morphs of males (bimorphism), which can show either a stained or clean chest. The chest becomes stained by secretions of the sternal gland during throat marking (rubbing throat and chest on a vertical substrate while smearing the scent deposition). The role of the chest staining in guiding female mate choice was previously hypothesized but never demonstrated probably due to the difficulty of observing sifaka copulations in the wild. Here we report that stained-chested males had a higher throat marking activity than clean-chested males during the mating season, but not during the birth season. We found that females copulated more frequently with stained-chested males than the clean-chested males. Finally, in agreement with the biological market theory, we found that clean-chested males, with a lower scent-releasing potential, offered more grooming to females. This “grooming for sex” tactic was not completely unsuccessful; in fact, half of the clean-chested males copulated with females, even though at low frequency. In conclusion, the chest stain, possibly correlated with different cues targeted by females, could be one of the parameters which help females in selecting mates

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 market fluctuations

Bioinformatics tools for cancer metabolomics

It is well known that significant metabolic change take place as cells are transformed from normal to malignant. This review focuses on the use of different bioinformatics tools in cancer metabolomics studies. The article begins by describing different metabolomics technologies and data generation techniques. Overview of the data pre-processing techniques is provided and multivariate data analysis techniques are discussed and illustrated with case studies, including principal component analysis, clustering techniques, self-organizing maps, partial least squares, and discriminant function analysis. Also included is a discussion of available software packages

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Biocuration - mapping resources and needs

Background: Biocuration involves a variety of teams and individuals across the globe. However, they may not self-identify as biocurators, as they may be unaware of biocuration as a career path or because biocuration is only part of their role. The lack of a clear, up-to-date profile of biocuration creates challenges for organisations like ELIXIR, the ISB and GOBLET to systematically support biocurators and for biocurators themselves to develop their own careers. Therefore, the ELIXIR Training Platform launched an Implementation Study in order to i) identify communities of biocurators, ii) map the type of curation work being done, iii) assess biocuration training, and iv) draw a picture of biocuration career development. Methods: To achieve the goals of the study, we carried out a global survey on the nature of biocuration work, the tools and resources that are used, training that has been received and additional training needs. To examine these topics in more detail we ran workshop-based discussions at ISB Biocuration Conference 2019 and the ELIXIR All Hands Meeting 2019. We also had guided conversations with selected people from the EMBL-European Bioinformatics Institute. Results: The study illustrates that biocurators have diverse job titles, are highly skilled, perform a variety of activities and use a wide range of tools and resources. The study emphasises the need for training in programming and coding skills, but also highlights the difficulties curators face in terms of career development and community building. Conclusion: Biocurators themselves, as well as organisations like ELIXIR, GOBLET and ISB must work together towards structural change to overcome these difficulties. In this article we discuss recommendations to ensure that biocuration as a role is visible and valued, thereby helping biocurators to proceed with their career.</p

Calmodulin expression distinguishes the smooth muscle cell population of human carotid plaque

Several observations suggest the expansion of a distinct medial smooth muscle cell (SMC) subset in atherosclerosis and restenosis. We characterized the phenotypic features of SMC subsets in cultures derived from human carotid endarterectomy specimens. Specimens comprised an undiseased portion (thin intimal thickening with the underlying media) and a diseased portion (atherosclerotic plaque with the underlying media). From plaque tissues of the diseased portion, only macrophage-derived foam cells were retrieved. From medial tissues, two SMC phenotypes were isolated: large SMCs (flat with a monolayered growth pattern, from the undiseased portion) and small SMCs (fusiform and growing in multilayers, from the undiseased and diseased portions after co-culture with macrophage-derived foam cells). Small SMCs displayed higher proliferative and migratory activities and were less differentiated than large SMCs. Proteomic analysis showed that calmodulin was predominant in small SMCs. Co-culture of large SMCs with macrophage-derived foam cells induced a transition to the small phenotype with increased calmodulin expression. The calmodulin inhibitor W-7 decreased the proliferation of small SMCs and prevented the large to small phenotypic transition. In vivo, calmodulin was markedly expressed in SMCs of atherosclerotic plaques and was barely detectable in the media. Macrophage-derived foam cells promote selective migration from the media of atheroma-prone SMCs characterized by calmodulin overexpression. Further studies of small SMCs could be instrumental in understanding atherosclerosis pathogenesis and in planning therapeutic strategies

Calmodulin Is a Marker of a Distinct Smooth Muscle Cell Population Recruited by Plaque-Derived Macrophages from the Human Carotid Artery Media

Background: Different experimental observations suggest the expansion of a distinct medial smooth muscle cell (SMC) subset during atheromatous plaque establishment and restenosis. Objectives: We investigated the presence and features of such SMC subset in cell cultures derived from human carotid endarterectomy (CEA) specimens; moreover, we aimed at finding markers that could play a role in SMC behavior. Methods and Results: CEA specimens comprised a grossly undiseased (UP) and a diseased portion (DP). The UP contained a thin intimal thickening with the underlying media and the DP an atherosclerotic plaque with the underlying media. Cell cultures were initiated by tissue explantation. From plaque tissues only macrophage-derived foam cells were retrieved. From medial tissues 2 distinct SMC phenotypes were identified: 1) large SMCs, flat with a monolayered growth pattern, isolated from the UP media; 2) small SMCs, fusiform and growing in multilayers, isolated from both the UP and DP media only when cocultured with plaque-derived macrophages. Small SMCs displayed higher proliferative and migratory activities and a poor level of differentiation compared with large SMCs. Two-dimensional polyacrylamide gel electrophoresis followed by tandem mass spectrometry showed that calmodulin (CaM), a calcium-binding protein involved in cell-cycle regulation, was mainly expressed in small SMCs. This result was confirmed using a specific CaM antibody. Coculture of large SMCs with plaque-derived macrophages induced a switch to the small phenotype and was associated with increased CaM expression. Consistently, the specific CaM inhibitor W-7 hampered the large-to-small switch and predominantly inhibited the proliferation of small SMCs. In vivo, CaM was markedly expressed in atherosclerotic plaques whereas it was barely detectable in the media. Conclusions: Plaque-derived macrophages promote the selective migration of a distinct SMC subpopulation exhibiting features of an "atheroma-prone" phenotype. CaM is a marker of small SMCs in vitro and of plaque SMCs in vivo, and plays a role in SMC phenotypic modulation. Further studies on these SMC populations can be instrumental in understanding and influencing the evolution of atherosclerosis