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Funding: This work was supported by a University of Kent 50th Anniversary Scholarship, and a Cotutelle de thèse grant from swissuniversities to J.V. Optimal foraging theory has guided much of the research on foraging behaviour in the past five decades, with the notion of optimality deeply embedded in most models today. However, assuming that all foragers strive to maximize a certain predefined currency, such as amount of food per unit time, restricts what can be learned about the factors influencing foraging decisions. Here we applied a different approach: the discrete-choice model, which does not assume an optimal strategy as the starting point, but instead examines foraging decisions directly, modelling interpatch movements as the consequence of a choice of destination from a limited set of options. We analysed a set of foraging decisions by both adult male and female chimpanzees, Pan troglodytes, from two habituated communities in the Budongo forest, Uganda, to investigate the influence of foraging variables including food patch characteristics and interpatch distance on patch choice, with a view to identifying the strategy underlying these decisions. Despite differences in habitat between communities, we found that foraging strategies were remarkably similar across both communities and sexes, with chimpanzees exhibiting a clear preference for closer and novel (not previously visited) food patches. Individuals of both communities frequently chose to forage on food patches providing young leaves, highlighting the importance of this food type in their diet. Contrary to expectation, patch size did not predict foraging decisions, except for adult males of one community that chose larger patches, while both sexes aimed to minimize travel distance between consecutive patches. This study provides the first direct evidence that chimpanzees consider travel distance and whether they have recently visited a patch when choosing between potential foraging sites and demonstrates that new insights can be gained (even in a well-studied system) from integrating several important variables describing feeding ecology into a coherent model of patch choice. Publisher PDF

Funding: J.L.P. thanks the University of St Andrews for funding and the Carnegie Trust for a Research Incentive Grant (RIG008653). The authors also thank EPSRC for funding (EP/T019298/1, EP/R023751/1 and EP/V034138/1). L.K.J. thanks UKRI for a Future Leaders Fellowship (MR/T022094/1). One of the great advantages of organic–inorganic metal halides is that their structures and properties are highly tuneable and this is important when optimizing materials for photovoltaics or other optoelectronic devices. One of the most common and effective ways of tuning the electronic structure is through anion substitution. Here, we report the inclusion of bromine into the layered perovskite [H3N(CH2)6NH3]PbBr4 to form [H3N(CH2)6NH3]PbBr4·Br2, which contains molecular bromine (Br2) intercalated between the layers of corner-sharing PbBr6 octahedra. Bromine intercalation in [H3N(CH2)6NH3]PbBr4·Br2 results in a decrease in the band gap of 0.85 eV and induces a structural transition from a Ruddlesden–Popper-like to Dion–Jacobson-like phase, while also changing the conformation of the amine. Electronic structure calculations show that Br2 intercalation is accompanied by the formation of a new band in the electronic structure and a significant decrease in the effective masses of around two orders of magnitude. This is backed up by our resistivity measurements that show that [H3N(CH2)6NH3]PbBr4·Br2 has a resistivity value of one order of magnitude lower than [H3N(CH2)6NH3]PbBr4, suggesting that bromine inclusion significantly increases the mobility and/or carrier concentration in the material. This work highlights the possibility of using molecular inclusion as an alternative tool to tune the electronic properties of layered organic–inorganic perovskites, while also being the first example of molecular bromine inclusion in a layered lead halide perovskite. By using a combination of crystallography and computation, we show that the key to this manipulation of the electronic structure is the formation of halogen bonds between the Br2 and Br in the [PbBr4]∞ layers, which is likely to have important effects in a range of organic–inorganic metal halides. Publisher PDF

A key benefit of grouping in prey species is access to social information, including information about the presence of predators. Larger groups of prey animals respond both sooner and at greater distances from predators, increasing the likelihood that group members will successfully avoid capture. However, identifying predators in complex environments is a difficult task, and false alarms (alarm behaviours without genuine threat) appear surprisingly frequent across a range of taxa including insects, amphibians, fish, mammals, and birds. In some bird flocks, false alarms have been recorded to substantially outnumber true alarms. False alarms can be costly in terms of both the energetic costs of producing alarm behaviours as well as lost opportunity costs (e.g. abandoning a feeding patch which was in fact safe, losing sleep if an animal is resting/roosting, or losing mating opportunities). Models have shown that false alarms may be a substantial but underappreciated cost of group living, introducing an inherent risk to using social information and a vulnerability to the propagation of false information. This review will focus on false alarms, introducing a two-stage framework to categorise the different factors hypothesised to influence the propensity of animal groups to produce false alarms. A number of factors may affect false alarm rate, and this new framework splits these factors into two core processing stages: (i) individual perception and response; and (ii) group processing of predator information. In the first stage, individuals in the group monitor the environment for predator cues and respond. The factors highlighted in this stage influence the likelihood that an individual will misclassify stimuli and produce a false alarm (e.g. lower light levels can make predator identification more difficult and false alarms more common). In the second stage, alarm information from individuals is processed by the group. The factors highlighted in this stage influence the likelihood of alarm information being copied by group members and propagated through the group (e.g. some animals implement group processing mechanisms that regulate the spread of behavioural responses such as consensus decision making through the quorum response). This review follows the structure of this new framework, focussing on the causes of false alarms, factors that influence false alarm rate, the transmission of alarm information through animal groups, mechanisms to mitigate the spread of false alarms, and the consequences of false alarms. Publisher PDF

Funding: AG acknowledges the UK-MRBT-CDT funded by EPSRC (EP/J500045/1), BEB acknowledges the Wellcome Trust Institutional Strategic Support fund (204821/Z/16/Z), JET acknowledges the Leverhulme Trust (Early Career Fellowship; ECF-2014-005). Nitroxides are a unique class of persistent radicals finding a wide range of applications, from spin probes to polarizing agents, and recently bis-nitroxides have been used as proof-of-concept molecules for quantum information processing. Here we present the syntheses of pyrroline-based nitroxide (NO) radicals and give a comparision of two possible synthetic routes to form two key intermediates, namely 2,2,5,5-tetramethylpyrroline-1-oxyl-3-acetylene (TPA) and 1-oxyl-2,2,5,5-tetramethylpyrroline-3-carboxylic acid (TPC). TPC and TPA were then used as precursors for the synthesis of three model compounds featuring two distant NO groups with a variable degree of conjugation and thus electronic communication between them. Using relatively facile synthetic routes, we produced a number of mono- and bis-nitroxides with the structures of multiple compounds unambiguously characterized by X-ray crystallography, while Continuous Wave Electron Paramagnetic Resonance (CW-EPR) allowed us quantify the electronic communication in the bis-nitroxides. Our study expands the repertoire of mono- and bis-nitroxides with possibilities of exploiting them for studying quantum coherence effects and as polarizing agents. Publisher PDF

Funding: British Heart Foundation (BHF): Research Excellence Award RE/13/3/30183; Kidney Research UK: Innovation Grant IN_001_201703 Postdoctoral Fellowship PDF_008_20151127; Scottish Funding Council (SFC): St Andrews Restarting Research Funding Scheme; Society for Endocrinology (SFE): Early Career Grant. We report the transcriptomes associated with acute corticosteroid regulation of ENaC activity in polarised mCCDcl1 collecting duct cells. 9 genes were regulated by aldosterone (ALDO), 0 with corticosterone alone and 151 with corticosterone when 11βHSD2 activity was inhibited. We validated 3 novel ALDO-induced genes: Rasd1, Sult1d1 and Gm43305 in primary cells isolated from a novel collecting duct reporter mouse. Background Corticosteroids regulate distal nephron and collecting duct Na+ reabsorption, contributing to fluid-volume and blood pressure homeostasis. The transcriptional landscape underpinning the acute stimulation of the epithelial sodium channel (ENaC) by physiological concentrations of corticosteroids remains unclear. Methods Transcriptomic profiles underlying corticosteroid-stimulated ENaC activity in polarised mCCDcl1 cells were generated by coupling electrophysiological measurements of amiloride-sensitive currents with RNAseq. Generation of a collecting-duct specific reporter mouse line, mT/mG-Aqp2Cre, enabled isolation of primary collecting duct cells by FACS and ENaC activity was measured in cultured primary cells following acute application of corticosteroids. Expression of target genes was assessed by qRT-PCR in cultured cells or freshly isolated cells following acute elevation of steroid hormones in mT/mG-Aqp2Cre mice. Results Physiological relevance of the mCCDcl1 model was confirmed with aldosterone-specific stimulation of SGK1 and ENaC activity. Corticosterone only modulated these responses at supraphysiological concentrations or when 11βHSD2 was inhibited. When 11βHSD2 protection was intact, corticosterone caused no significant change in transcripts. We identified a small number of aldosterone-induced transcripts associated with stimulated ENaC activity in mCCDcl1 cells and a much larger number with corticosterone in the absence of 11βHSD2 activity. Cells isolated from mT/mG-Aqp2Cre mice were validated as collecting duct-specific and assessment of identified aldosterone-induced genes revealed that Sgk1, Zbtbt16, Sult1d1, Rasd1 and Gm43305 are acutely upregulated by corticosteroids both in vitro and in vivo. Conclusions This study reports the transcriptome of mCCDcl1 collecting duct cells and identifies a small number of aldosterone-induced genes associated with acute stimulation of ENaC, including 3 previously undescribed genes. Postprint

Authors thank the Royal Zoological Society Scotland for the core funding they provide to the Budongo Conservation Field Station. Associating with kin provides individual benefits but requires that these relationships be detectable. In humans, facial phenotype matching might help assess paternity; however, evidence for it is mixed. In chimpanzees, concealing visual cues of paternity may be beneficial due to their promiscuous mating system and the considerable risk of infanticide by males. On the other hand, detecting kin can also aid chimpanzees in avoiding inbreeding and in forming alliances that improve kin-mediated fitness. Although previous studies assessing relatedness based on facial resemblance in chimpanzees exist, they used images of captive populations in whom selection pressures and reproductive opportunities are controlled and only assessed maternity or paternity of adult offspring. In natural populations, the chances of infanticide are highest during early infancy, suggesting that young infants would benefit most from paternity concealment, whereas adults and subadults would benefit from the detection of all types of kin, including half-siblings. In our experiment, we conducted an online study with human participants, in which they had to assess the relatedness of chimpanzees based on facial similarity. To address previous methodological constraints, we used chimpanzee images across all ages, as well as maternal and paternal half-siblings. We found that kin status was detected above chance across all relatedness categories, with easier kin detection of father-offspring pairs, females, and older chimpanzees. Together, these findings support the existence of paternity confusion in infant chimpanzees and provide a possible mechanism for incest avoidance and kin-based social alliances in older individuals. Postprint

Funding: Systematics Research Fund 2019 to KV. John Templeton Foundation (Grant Number(s): #60501; Grant recipient(s): Kevin N Laland). 1. The size of a bird's nest can play a key role in ensuring reproductive success and is determined by a variety of factors. The primary function of the nest is to protect offspring from the environment and predators. Field studies in a number of passerine species have indicated that higher-latitude populations in colder habitats build larger nests with thicker walls compared to lower-latitude populations, but that these larger nests are more vulnerable to predation. Increases in nest size can also be driven by sexual selection, as nest size can act as a signal of parental quality and prompt differential investment in other aspects of care. It is unknown, however, how these microevolutionary patterns translate to a macroevolutionary scale. 2. Here, we investigate potential drivers of variation in the outer and inner volume of open cup nests using a large dataset of nest measurements from 1117 species of passerines breeding in a diverse range of environments. Our dataset is sourced primarily from the nest specimens at the Natural History Museum (UK), complemented with information from ornithological handbooks and online databases. 3. We use phylogenetic comparative methods to test long-standing hypotheses about potential macroevolutionary correlates of nest size, namely nest location, clutch size and variables relating to parental care, together with environmental and geographical factors such as temperature, rainfall, latitude and insularity. 4. After controlling for phylogeny and parental body size, we demonstrate that the outer volume of the nest is greater in colder climates, in island-dwelling species and in species that nest on cliffs or rocks. By contrast, the inner cup volume is associated solely with average clutch size, increasing with the number of chicks raised in the nest. We do not find evidence that nest size is related to the length of parental care for nestlings. 5. Our study reveals that the average temperature in the breeding range, along with several key life-history traits and proxies of predation threat, shapes the global interspecific variation in passerine cup nest size. We also showcase the utility of museum nest collections—a historically underused resource—for large-scale studies of trait evolution. Publisher PDF

Funding: RKH thanks the Perry Foundation and the University of St Andrews for funding. AJK is supported by the strategic research program funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division. Facultative endosymbionts can induce benefits and costs to their aphid hosts. In the pea aphid, Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae), infection with the γ-proteobacterium Hamiltonella defensa Moran et al. can confer resistance against parasitoids, but may also reduce the frequency of aggressive and escape behaviours exhibited in response to predators. In potato aphids, Macrosiphum euphorbiae (Thomas) (Hemiptera: Aphididae), H. defensa does not appear to influence susceptibility to parasitism, but its impact on anti-predator behaviours remains unexplored. Here we investigated defensive behaviours in two pea aphid lines (differing in H. defensa-infection status) and four potato aphid lines (that additionally differed in genotype-associated parasitism susceptibility) when faced with foraging ladybirds – Adalia bipunctata (L.) (Coleoptera: Coccinellidae) – and lacewings Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae). In response to ladybirds, symbiont-infected pea aphids exhibited proportionately fewer evasive defences (dropping and walking away) than non-infected (cured) pea aphids, but more frequent aggressive kicking. Ladybirds provoked more evasive, aggressive, and total defensive behaviours than lacewings. For potato aphids, symbiont status, predator type, and aphid genotype (i.e., assumed parasitism susceptibility) all influenced behavioural repertoires. Overall, infected lines showed greater differentiation in behaviours in response to the two predators than the uninfected lines. The presence of the symbiont H. defensa may be a key determinant of aphid anti-predator behaviours, but the fitness consequences of this are unresolved. In our study, neither symbiont infection status nor aphid genotype affected the number of aphids consumed by predators. Publisher PDF

Funding: This work was supported by Fisheries and Oceans Canada (DFO) Maritimes and National Geographic emerging explorer grant to L.J.F, with support by and Natural Sciences and Engineering Research Council of Canada (NSERC) and Killam Nova Scotia Doctoral Scholarships. Work was also supported by US Office of Naval Research and US Strategic Environmental Research and Development Program (SERDP), DFO, University of Windsor, Crown-Indigenous Relations and Northern Affairs Canada, Nunavut Fisheries Association, Government of Nunavut, and NSERC. Funding and resources for sequencing the northern bottlenose whale genome was supported by the CanSeq150 program of Canada’s Genomics Enterprise. Information on wildlife population structure, demographic history, and adaptations are fundamental to understanding species evolution and informing conservation strategies. To study this ecological context for a cetacean of conservation concern, we conducted the first genomic assessment of the northern bottlenose whale, Hyperoodon ampullatus, using whole-genome resequencing data (n = 37) from five regions across the North Atlantic Ocean. We found a range-wide pattern of isolation-by-distance with a genetic subdivision distinguishing three subgroups: the Scotian Shelf, western North Atlantic, and Jan Mayen regions. Signals of elevated levels of inbreeding in the Endangered Scotian Shelf population indicate this population may be more vulnerable than the other two subgroups. In addition to signatures of inbreeding, evidence of local adaptation in the Scotian Shelf was detected across the genome. We found a long-term decline in effective population size for the species, which poses risks to their genetic diversity and may be exacerbated by the isolating effects of population subdivision. Protecting important habitat and migratory corridors should be prioritized to rebuild population sizes that were diminished by commercial whaling, strengthen gene flow, and ensure animals can move across regions in response to environmental changes. Publisher PDF

Funding: This work was funded by the Office of Naval Research under award: N000141912464. 1. The assessment of behavioural disturbance in cetacean species (e.g., resulting from exposure to anthropogenic sources such as military sonar, seismic surveys, or pile driving) is important for effective conservation and management. Disturbance effects can be informed by Behavioural Response Studies (BRSs), involving either controlled exposure experiments (CEEs) where noise exposure conditions are presented deliberately to meet experimental objectives or in opportunistic contexts where ongoing activities are monitored in a strategic manner. In either context, animal-borne sensors or in-situ observations can provide information on individual exposure and disturbance responses. 2. The past 15 years of research have greatly expanded our understanding of behavioural responses to noise, including hundreds of experiments in nearly a dozen cetacean species. Many papers note limited sample sizes, required knowledge of baseline behaviour prior to exposure and the importance of contextual factors modulating behavioural responses, all of which in combination can lead to sampling biases, even for well-designed research programs. 3. It is critical to understand these biases to robustly identify responses. This ensures outcomes of BRSs help inform predictions of how anthropogenic disturbance impacts individuals and populations. Our approach leverages concepts from the animal behaviour literature focused on helping to avoid sampling bias by considering what shapes an animal's response. These factors include social, experience, genetic and natural changes in responsiveness. 4. We developed and applied a modified version of this framework to synthesize current knowledge on cetacean response in the context of effects observed across marine and terrestrial taxa. This new 'Sampling, Exposure, Receptor' framework (SERF) identifies 43 modulating factors, highlights potential biases, and assesses how these vary across selected focal species. 5. In contrast to studies that identified variation in 'Exposure' factors as a key concern, our analysis indicated that factors relating to 'Sampling' (e.g., deploying tags on less evasive individuals, which biases selection of subjects), and "Receptor" (e.g., health status or coping style) have the greatest potential for weakening the desired broad representativeness of BRSs. Our assessment also highlights how potential biases could be addressed with existing datasets or future developments. Publisher PDF

The study was funded by a St Leonard College Inter-University scholarship awarded to JC and KZ, the Swiss National Science Foundation awarded to KZ (310030_185324), and individual grants from Swiss universities and St Leonard Santander Mobility awarded to AS. Audience effects are key in studies of animal social cognition and are typically investigated during directed social interactions. Male chimpanzees regularly perform aggressive displays in the presence of others, often targeting a specific group member, and combine this agonistic behaviour with acoustic signals. Here, we were interested in whether the production and structure of pant hoots, a long-distance signal, were influenced by audience composition (i.e., presence and absence of specific individuals). We investigated pant hoots produced during displays by adult and sub-adult males of Budongo Forest, Uganda. We found that males overall called more often when their preferred social partners and females were absent from the party, as well as when more dominant males were present. We then separately analysed the four phases of pant hoots - introduction, build-up, climax, and let-down - and found that audience composition and social context could often explain the presence or absence of each phase. In addition, displays were often accompanied by drumming, especially by older males and when male audiences were small. Our study adds to the growing body of literature on audience effects and other social factors and shows their impact on the structure of a sophisticated vocal sequence, which enhances the communicative capacity in a species with limited vocal control. Publisher PDF

In the two-cup one-item task, subjects are shown a food item, which is then hidden inside one of two cups. Several species spontaneously select the baited cup above chance levels if shown that the other cup is empty. Although this response may indicate inference by exclusion (if not A, then B), another possibility is that subjects simply avoid choosing the empty cup, not because they expect the food to be in the other cup but because they have seen that cup to be empty. I tested whether this hypothesis explains great apes' responses in a three-cup one-item task. Subjects saw three opaque cups on a platform, with two of them located behind a barrier during baiting. After baiting one of the cups behind the barrier, I revealed the identity of the empty cup that had been located behind the barrier (Experiment 1) or revealed the contents of the center cup (baited in half of the trials), but always removed it before the subjects' choice (Experiment 2). In Experiment 1, subjects preferentially selected the baited cup even though one of the other two cups had not been shown to be empty. In Experiment 2, subjects' preference for the cup that had been located behind the barrier during baiting was modulated by the contents of the removed cup. These results suggest that expectations about the food's location, not just the sight of the empty cup, as postulated by the "avoid the empty cup" hypothesis, determine apes' responses in the three-cup one-item task. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Daphne Cortese, Amelia Munson and Shaun S. Kille are supported by Natural Environment Research Council Standard Grant NE/T008334/1 awarded to Shaun S. Killen. Libor Závorka was supported by Austrian Science Fund Stand Alone Project P35515-B. While studies on fish cognition are increasing, consideration of how methodological details influence the ability to detect and measure performance is lagging. Here, in two separate experiments we compared latency to leave the start position, latency to make a decision, levels of participation and success rates (whether fish entered the rewarded chamber as first choice) across different physical designs. Experiments compared fish performance across 1) two sizes of T-mazes, large and standard, and a plus-maze, and 2) open choice arenas with either two or four doors. Fish in T-mazes with longer arms took longer to leave the start chamber and were less likely to participate in a trial than fish in T-mazes with shorter arms. The number of options, or complexity, in a maze significantly impacted success, but did not necessarily impact behavioural measures, and did not impact the number of fish that reached a chamber. Fish in the plus-maze had similar latencies to leave the start box and time to reach any chamber as fish in the same sized T-maze but exhibited lower overall success. Similarly, in an open choice arena, increasing the number of options – doors to potential reward chambers- resulted in lower probability of success. There was an influence of reward position in the choice arena, with rewarded chambers closest to the sides of the arena resulting in lower latencies to enter and higher probability of decision success. Together our results allow us to offer practical suggestions towards optimal maze design for studies of fish cognition. Publisher PDF

Funding: Horizon 2020 FETOPEN, GRANT #(s) 863203; European Union FAMOS, GRANT #(s) 317744; UK Engineering and Physical Engineering and Physical Sciences Research Council (EPSRC) EP/M000869/1 and EP/P030017/1; Australian Research Council, FUNDREF 10.13039/501100000923, GRANT #(s) FL210100099; Horizon 2020 Framework Programme, FUNDREF 10.13039/100010661, GRANT #(s) 871212. The penetration depth of optical coherence tomography (OCT) reaches well beyond conventional microscopy; however, signal reduction with depth leads to rapid degradation of the signal below the noise level. The pursuit of imaging at depth has been largely approached by extinguishing multiple scattering. However, in OCT, multiple scattering substantially contributes to image formation at depth. Here, we investigate the role of multiple scattering in OCT image contrast and postulate that, in OCT, multiple scattering can enhance image contrast at depth. We introduce an original geometry that completely decouples the incident and collection fields by introducing a spatial offset between them, leading to preferential collection of multiply scattered light. A wave optics–based theoretical framework supports our experimentally demonstrated improvement in contrast. The effective signal attenuation can be reduced by more than 24 decibels. Notably, a ninefold enhancement in image contrast at depth is observed in scattering biological samples. This geometry enables a powerful capacity to dynamically tune for contrast at depth. Publisher PDF

The present paper provides an integrative theory of actions and motor programs for skill in tool use, construction, and language. We analyze preconditions for action as well as making their effects (postconditions) explicit, emphasizing the “how” of action details as well as the “what” of motor programs, aided by conceptual analysis of several brain modeling efforts. The theory is exemplified by analysis of the subtractive construction involved in percussive tooling by capuchin monkeys and Oldowan and Acheulean stone tool by protohumans making before turning to the additive construction of hafted tools. A complementary analysis focused on the construction of bird nests explores the notion of “image” and “stage” in construction. We offer a brief comparison with birdsong before arguing for a very different relation between communication and construction in humans. Pantomime lifts manipulation from practical to communicative action in protohumans, and we consider the role of pedagogy before offering hypotheses on the emergence of human language that suggest how language may have evolved from manual skills. We note that language provides an open-ended means for devising innovations in tool use and construction, but reiterate the importance of this framework for diverse future studies in ethology and comparative psychology. Publisher PDF

The Oticon Foundation and theOcean Futures/Free Willy Keiko Foundation provided funding and platforms for data collection in Vestmannaeyjar 2002. Funding for data collection in Vestmannaeyjar from 2008 onwards and in Breiðafjörður was provided by the BBC Natural History Unit, Fundaç ̃ao para a Ciência e a Tecnologia (grant number SFRH/BD/30303/2006), the Icelandic Centre for Research through a START Postdoctoral Fellowship (grant number 120248042) and Project Grant (grant number 163060), the National Geographic Global Exploration Fund (grant number GEFNE65-12), a Marie Curie International Incoming Fellowship (project number 297116), the Office of Naval Research (grant number N00014-08-1-0984), and a Russell Trust Award from the University of St Andrews. A.S. was supported by a Doctoral Student Grant (grant number 206808) from the Icelandic Centre for Research. V.B.D. was supported by a grant from the University of Cumbria's Research and Scholarship Development Fund. E.M. was supported by the Doctoral Grants of the University of Iceland Research Fund (grant number 200913) and the Conservation Fund of Pálmi Jonasson. This project was funded in part by the generous support of Earthwatch. Killer whales (Orcinus orca) have group-specific call repertoires that can be used to track groups and populations using passive acoustic monitoring. To provide a detailed description of the Icelandic killer whale repertoire and its variation, we analyzed acoustic data collected in five locations between 1985 and 2016. Calls were classified manually, and CART and random forest analyses were employed to validate the manual classification. A total of 91 call categories (including call types and subtypes) were defined. Most call categories were recorded in more than one location, with the highest proportion shared between herring grounds in Vestmannaeyjar (South) and Breiðafjörður (West). However, both locations included call categories that were not recorded elsewhere in Iceland. Recordings from past herring wintering grounds in eastern Iceland included few call categories that matched other locations. Sample sizes from Reykjanes (Southwest) and Skjálfandi (North) were small and did not include unique call categories. The relative occurrence of call categories in Vestmannaeyjar changed little over a 14-year period (2002-2016), although shorter-term changes between years were observed that appeared to correlate to changes in individuals identified. This comparison of acoustic repertoires provides valuable information on the social structure and movement patterns of herring-eating killer whales around Iceland. Publisher PDF

Funding: This work was supported by the Vienna Science and Technology Fund (WWTF) (10.47379/MA16061). C.K. received funding from the Royal Society (RG170315) and the Carnegie Trust (RIG007474). M.G.R. and R.R.S. have been supported by NERC (UK) grants NE/I014632/1 and NE/V001566/1. Bioinformatics analyses were performed on the computer cluster at the University of St Andrews Bioinformatics Unit, which is funded by Wellcome Trust ISSF awards 105621/Z/14/Z. Complementary data parsing was carried out with the computational resources provided by the Research/Scientific Computing teams at The James Hutton Institute and the National Institute of Agricultural Botany (NIAB)—UK’s Crop Diversity Bioinformatics HPC, BBSRC grant BB/S019669/1. Experimental evolution studies are powerful approaches to examine the evolutionary history of lab populations. Such studies have shed light on how selection changes phenotypes and genotypes. Most of these studies have not examined the time course of adaptation under sexual selection manipulation, by resequencing the populations’ genomes at multiple time points. Here, we analyze allele frequency trajectories in Drosophila pseudoobscura where we altered their sexual selection regime for 200 generations and sequenced pooled populations at 5 time points. The intensity of sexual selection was either relaxed in monogamous populations (M) or elevated in polyandrous lines (E). We present a comprehensive study of how selection alters population genetics parameters at the chromosome and gene level. We investigate differences in the effective population size—Ne—between the treatments, and perform a genome-wide scan to identify signatures of selection from the time-series data. We found genomic signatures of adaptation to both regimes in D. pseudoobscura. There are more significant variants in E lines as expected from stronger sexual selection. However, we found that the response on the X chromosome was substantial in both treatments, more pronounced in E and restricted to the more recently sex-linked chromosome arm XR in M. In the first generations of experimental evolution, we estimate Ne to be lower on the X in E lines, which might indicate a swift adaptive response at the onset of selection. Additionally, the third chromosome was affected by elevated polyandry whereby its distal end harbors a region showing a strong signal of adaptive evolution especially in E lines. Publisher PDF

Funding: PLT received support from ONR grants N00014-18-1-2062 and N00014-20-1-2709. Financial support for the whistle database project has come from the Protect Wild Dolphins fund at Harbor Branch Oceanographic Institute, Vulcan Machine Learning Center for Impact, Allen Institute for Artificial Intelligence, Adelaide M. & Charles B. Link Foundation, and Dolphin Quest, Inc. Human caregivers interacting with children typically modify their speech in ways that promote attention, bonding, and language acquisition. Although this “motherese,” or child-directed communication (CDC), occurs in a variety of human cultures, evidence among nonhuman species is very rare. We looked for its occurrence in a nonhuman mammalian species with long-term mother–offspring bonds that is capable of vocal production learning, the bottlenose dolphin (Tursiops truncatus). Dolphin signature whistles provide a unique opportunity to test for CDC in nonhuman animals, because we are able to quantify changes in the same vocalizations produced in the presence or absence of calves. We analyzed recordings made during brief catch-and-release events of wild bottlenose dolphins in waters near Sarasota Bay, Florida, United States, and found that females produced signature whistles with significantly higher maximum frequencies and wider frequency ranges when they were recorded with their own dependent calves vs. not with them. These differences align with the higher fundamental frequencies and wider pitch ranges seen in human CDC. Our results provide evidence in a nonhuman mammal for changes in the same vocalizations when produced in the presence vs. absence of offspring, and thus strongly support convergent evolution of motherese, or CDC, in bottlenose dolphins. CDC may function to enhance attention, bonding, and vocal learning in dolphin calves, as it does in human children. Our data add to the growing body of evidence that dolphins provide a powerful animal model for studying the evolution of vocal learning and language. Publisher PDF

Funding: CMC and CJH are funded by the Wellcome Trust (210486/Z/18/Z), additional funding was provided by the University of St Andrews Impact Innovation Fund. MB (Bergkessel) is funded by the University of Dundee/Wellcome Trust Institutional Strategic Support Fund [204816/Z/16/Z] and UKRI Future Leaders Fellowship (funded by the Medical Research Council) [MR/T041811/1]. Pseudomonas aeruginosa is an opportunistic pathogen that causes serious illness, especially in immunocompromised individuals. P. aeruginosa forms biofilms that contribute to growth and persistence in a wide range of environments. Here we investigated the aminopeptidase, P. aeruginosa aminopeptidase (PaAP) from P. aeruginosa, which is highly abundant in the biofilm matrix. PaAP is associated with biofilm development and contributes to nutrient recycling. We confirmed that post-translational processing was required for activation and PaAP is a promiscuous aminopeptidase acting on unstructured regions of peptides and proteins. Crystal structures of wild-type enzymes and variants revealed the mechanism of autoinhibition, whereby the C-terminal propeptide locks the protease-associated domain and the catalytic peptidase domain into a self-inhibited conformation. Inspired by this, we designed a highly potent small cyclic-peptide inhibitor that recapitulates the deleterious phenotype observed with a PaAP deletion variant in biofilm assays and present a path toward targeting secreted proteins in a biofilm context. Publisher PDF

This research would not have been possible without the generous EPSRC stipend; we are very grateful for the awarding of this studentship to Alan Scaramangas. Our understanding of aposematism (the conspicuous signalling of a defence for the deterrence of predators) has advanced notably since its first observation in the late nineteenth century. Indeed, it extends the scope of a well-established game-theoretical model of this very same process both from the analytical standpoint (by considering regimes of varying background mortality and colony size) and from the practical standpoint (by assessing its efficacy and limitations in predicting the evolution of prey traits in finite simulated populations). The nature of the manuscript at hand is more mathematical and it’s aim is two-fold: first, to determine the relationship between evolutionarily stable levels of defence and signal strength under various regimes of background mortality and colony size. Second, to compare these predictions with simulations of finite prey populations that are subject to random local mutation. We compare the roles of absolute resident fitness, mutant fitness and stochasticity in the evolution of prey traits and discuss the importance of population size in the above. Publisher PDF

Individuals with a history of depression have an increased risk for future episodes. This risk has been linked with impaired features of autobiographical memory retrieval that remain when depressive symptoms abate, including memory specificity, remoteness, valence, and vantage perspective. Rumination has been shown to influence these impairments and can be reduced via compassion training. We therefore investigated the effects of a self-compassion meditation on autobiographical memory retrieval in remitted depression. Baseline data were collected (n = 50) using an extended version of the Autobiographical Memory Test where participants with remitted depression retrieved specific memories from a remote time period (10 cues) and from any time period (10 cues). Valence and vantage perspective were rated. Participants were then randomly allocated to a self-compassion meditation or (control) colouring intervention group. Baseline measures were reassessed after four weeks of the intervention. Results revealed increased retrieval of specific memories in the self-compassion group in comparison to the colouring group, and an increase in positive and field memories across groups while no remoteness changes were observed. This self-compassion meditation demonstrated initial promise as an intervention to influence features of autobiographical memory retrieval in remitted depression. Improvements were shown in specificity, valence, and vantage perspective. Addressing these features with this type of intervention might reduce a cognitive vulnerability to depression and should be investigated in future studies. Publisher PDF

The causes of sex differences in human behaviour are contested, with ‘evolutionary’ and ‘social’ explanations often being pitted against each other in the literature. Recent work showing positive correlations between indices of gender equality and the size of sex differences in behaviour has been argued to show support for ‘evolutionary’ over ‘social’ approaches. This argument, however, neglects the potential for social learning to generate arbitrary gender segregation. In the current paper we simulate, using agent-based models, a population where agents exist as one of two ‘types’ and can use social information about which types of agents are performing which ‘roles’ within their environment. We find that agents self-segregate into different roles even where real differences in performance do not exist, if there is a common belief (modelled as priors) that group differences may exist in ‘innate’ competence. Facilitating role changes such that agents should move without cost to the predicted highest-rewards for their skills (i.e. fluidity of the labour market) reduced segregation, while forcing extended exploration of different roles eradicated gender segregation. These models are interpreted in terms of bio-cultural evolution, and the impact of social learning on the expression of gender roles. Publisher PDF

Funding: Matthias Waibel was funded by the University of Galway College of Science and the Irish Research Council under GOIPG/2016/1215. The James Hutton Institute receives funding support from the Rural and Environment Science and Analytical Services Division of the Scottish Government. Open access funding provided by IReL. Soil organic matter (SOM) is biologically, chemically, and physically complex. As a major store of nutrients within soil, it plays an important role in nutrient provision to plants. An enhanced understanding of SOM utilisation processes could underpin better fertiliser management for plant growth, with reduced environmental losses. Metaproteomics can allow the characterisation of protein profiles and could help gaining insights into SOM microbial decomposition mechanisms. Here, we applied three different extraction methods to two soil types to recover SOM with different characteristics. Specifically, water extractable organic matter, mineral associated organic matter and protein-bound organic matter were targeted with the aim to investigate the metaproteome enriched in those extractions. As a proof-of-concept replicated extracts from one soil were further analysed for peptide identification using liquid chromatography followed by tandem mass spectrometry. We employ a framework for mining mass spectra for both peptide assignment and fragmentation pattern characterisation. Different extracts were found to exhibit contrasting total protein and humic substance content for the two soils investigated. Overall, water extracts displayed the lowest humic substance content (in both soils) and the highest number of peptide identifications (in the soil investigated) with most frequent peptide hits associated with diverse substrate/ligand binding proteins of Proteobacteria and derived taxa. Our framework also highlighted a strong peptidic signal in unassigned and unmatched spectra, information that is currently not captured by the pipelines employed in this study. Taken together, this work points to specific areas for optimisation in chromatography and mass spectrometry to adequately characterise SOM associated metaproteomes. Publisher PDF

Some data are collected on circular (rather than linear) scales. Often researchers are interested in comparing two samples of such circular data to test the hypothesis that they came from the same underlying population. Recently, we compared 18 statistical approaches to testing such a hypothesis, and recommended two as particularly effective. A very recent publication introduced a novel statistical approach that was claimed to outperform the methods that we had indicated were highest performing. However, the evidence base for this claim was limited. Here we perform simulation studies to offer a more detailed comparison of the new “Angular Randomisation Test” (ART) with existing tests. We expand previous evaluations in two ways: exploring small and medium sized samples, and exploring a range of different shapes for the underlying distribution(s). We find that the ART controls type I error rates at the nominal level. The ART had greater power than established methods in detecting a difference in underlying distribution caused by a shift around the circle. Its performance advantage in this case was strongest when samples where small and unbalanced in size. When the difference between underlying unimodal distributions was in shape rather than central tendency, then the ART was at least as good (and sometimes considerably more powerful) than the established methods, except when distributions samples were small and uneven in size, and the smaller sample came from a more concentrated underlying distribution. In such cases its power could be markedly inferior to established alternatives. The ART was also inferior to alternatives in dealing with axially distributed data. We conclude that under widely-encountered circumstances the ART test can be recommended for its simplicity of implementation, but researchers should be aware of situations where it cannot be recommended. Grant Number: P32586 to LL. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. EPM receives funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 948728). EPM acknowledges the HPC facility at the Max Planck Institute for Neurobiology of Behavior—caesar.

Funding: This work was supported by the British Heart Foundation (grant code: PG/21/10468, FS/19/69/34639) and the Biotechnological and Biological Sciences Research Council (grant code: BB/V014684/1). Increasing evidence suggests that Zn2+ acts as a second messenger capable of transducing extracellular stimuli into intracellular signalling events. The importance of Zn2+ as a signalling molecule in cardiovascular functioning is gaining traction. In the heart, Zn2+ plays important roles in excitation-contraction (EC) coupling, excitation-transcription coupling, and cardiac ventricular morphogenesis. Zn2+ homeostasis in cardiac tissue is tightly regulated through the action of a combination of transporters, buffers and sensors. Zn2+-mishandling is a common feature of various cardiovascular diseases. However, the precise mechanisms controlling the intracellular distribution of Zn2+ and its variations during normal cardiac function and during pathological conditions are not fully understood. In this review we consider the major pathways by which the concentration of intracellular Zn2+ is regulated in the heart, the role of Zn2+ in EC coupling and discuss how Zn2+-dyshomeostasis resulting from altered expression levels and efficacy of Zn2+ regulatory proteins are key drivers in the progression of cardiac dysfunction. Publisher PDF

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Funding: This article is a contribution of the COVID-19 Bio-Logging Initiative, which is funded in part by the Gordon and Betty Moore Foundation (GBMF9881) and the National Geographic Society (NGS-82515R-20) (both grants to C.R.). COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals’ 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide. Postprint

Funding: This research was supported by a European Research Council Consolidator (grant no. 771387). Recent years have seen renewed interest in the role of religious systems as drivers of the evolution of cooperation in human societies. One suggestion is that a cultural tradition of ancestor worship might have evolved as a "descendant-leaving strategy" of ancestors by encouraging increased altruism particularly between distant kin. Specifically, Coe and others have suggested a mechanism of cultural transmission exploiting social learning biases, whereby ancestors have been able to establish parental manipulation of kin recognition and perceived relatedness as a traditional behavior, leading to increased altruism among co-descendants and thereby maximizing the ancestor’s long-term inclusive fitness. Here, we develop a demographically explicit model in order to quantify the resulting increase in altruism and concomitant “ancestor-descendant conflict”, and to determine the evolutionary feasibility of religiously motivated cultural norms that promote altruism among co-descendants. Our analysis reveals that such norms could indeed drive an overall increase in altruism with potential for ancestor-descendant conflict, particularly in low-dispersal settings. Moreover, we find that natural selection can favor traditions encouraging increased altruism towards co-descendants under a range of conditions, with the inclusive-fitness costs of enacting an inappropriately high level of altruism being offset by inclusive-fitness benefits derived from the cultural tradition facilitating kin recognition. Publisher PDF

When facing uncertainty, humans often build mental models of alternative outcomes. Considering diverging scenarios allows agents to respond adaptively to different actual worlds by developing contingency plans (covering one's bases). In a pre-registered experiment, we tested whether chimpanzees (Pan troglodytes) prepare for two mutually exclusive possibilities. Chimpanzees could access two pieces of food, but only if they successfully protected them from a human competitor. In one condition, chimpanzees could be certain about which piece of food the human experimenter would attempt to steal. In a second condition, either one of the food rewards was a potential target of the competitor. We found that chimpanzees were significantly more likely to protect both pieces of food in the second relative to the first condition, raising the possibility that chimpanzees represent and prepare effectively for different possible worlds. Postprint

Funding: Authors acknowledge the funding from UKRI Future Leaders Fellowship (MR/W007460/1). A.M. thanks the University of St Andrews (Impact & Innovation Fund) for funding. M.T. and J.C.T. thank the ERC Consolidator Grant (PROMOFS grant agreement 771575) for funding the research. ABN gratefully acknowledges funding from the EPSRC through grant numbers EP/L017008/1, EP/R023751/1 and EP/T019298/1. We report here the synthesis of polyureas from the dehydrogenative coupling of diamines and diformamides. The reaction is catalysed by a manganese pincer complex and releases H2 gas as the only by-product making the process atom-economic and sustainable. The reported method is greener in comparison to the current state-of-the-art production routes that involve diisocyanate and phosgene feedstock. We also report here the physical, morphological, and mechanical properties of synthesized polyureas. Based on our mechanistic studies, we suggest that the reaction proceeds via isocyanate intermediates formed by the manganese catalysed dehydrogenation of formamides. Publisher PDF

Funding: Engineering and Physical Sciences Research Council - EP/P030017/1, EP/R004854/1; Australian Research Council - FL210100099; National Health and Medical Research Council - APP2003786; Future Making Fellowship (University of Adelaide); Hospital Research Foundation (Mid-career fellowship C-MCF58-2019). Embryo quality is a crucial factor affecting live birth outcomes. However, an accurate diagnostic for embryo quality remains elusive in the in vitro fertilization clinic. Determining physical parameters of the embryo may offer key information for this purpose. Here, we demonstrate that digital holographic microscopy (DHM) can rapidly and non-invasively assess the refractive index of mouse embryos. Murine embryos were cultured in either low- or high-lipid containing media and digital holograms recorded at various stages of development. The phase of the recorded hologram was numerically retrieved, from which the refractive index of the embryo was calculated. We showed that DHM can detect spatio-temporal changes in refractive index during embryo development that are reflective of its lipid content. As accumulation of intracellular lipid is known to compromise embryo health, DHM may prove beneficial in developing an accurate, non-invasive, multimodal diagnostic. Publisher PDF

Funding: The authors gratefully acknowledge the China Scholarship Council for funding a PhD scholarship for D. W. This work was also funded by the Leverhulme Trust (grant no. RPG-2017-214). I. G. S., W. M. and M. G. were funded by NIH grant R01-GM132595 and Harrison Family Funds. M. P. C. acknowledges the support of a Robert R. Wagner Fellowship at the University of Virginia. R. F. was supported by the Biological and Biotechnological Sciences Research Council (grant no. BB/V014684/1). Serum albumin–Co2+ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are central to the albumin cobalt binding (ACB) assay for diagnosis of myocardial ischemia. To further understand these processes, a deeper understanding of albumin–Co2+ interactions is required. Here, we present the first crystallographic structures of human serum albumin (HSA; three structures) and equine serum albumin (ESA; one structure) in complex with Co2+. Amongst a total of sixteen sites bearing a cobalt ion across the structures, two locations were prominent, and they relate to metal-binding sites A and B. Site-directed mutagenesis and isothermal titration calorimetry (ITC) were employed to characterise sites on HSA. The results indicate that His9 and His67 contribute to the primary (putatively corresponding to site B) and secondary Co2+-binding sites (site A), respectively. The presence of additional multiple weak-affinity Co2+ binding sites on HSA was also supported by ITC studies. Furthermore, addition of 5 molar equivalents of the non-esterified fatty acid palmitate (C16:0) reduced the Co2+-binding affinity at both sites A and B. The presence of bound myristate (C14:0) in the HSA crystal structures provided insight into the fatty acid-mediated structural changes that diminish the affinity of the protein toward Co2+. Together, these data provide further support for the idea that ischemia-modified albumin corresponds to albumin with excessive fatty-acid loading. Collectively, our findings provide a comprehensive understanding of the molecular underpinnings governing Co2+ binding to serum albumin. Publisher PDF

Abstract Primates understand the meaning of their own and other species’ alarm calls, but little is known about how they acquire such knowledge. Here, we combined direct behavioural observations with playback experiments to investigate two key processes underlying vocal development: comprehension and usage. Especifically, we studied the development of con- and heterospecific alarm call recognition in free-ranging sooty mangabeys, Cercocebus atys, across three age groups: young juveniles (1–2y), old juveniles (3–4y) and adults (> 5y). We observed that, during natural predator encounters, juveniles alarm called to a significantly wider range of species than adults, with evidence of refinement during the first four years of life. In the experiments, we exposed subjects to leopard, eagle and snake alarm calls given by other group members or sympatric Diana monkeys. We found that young juveniles’ locomotor and vocal responses were least appropriate and that they engaged in more social referencing (look at adults when hearing an alarm call) than older individuals, suggesting that vocal competence is obtained via social learning. In conclusion, our results suggest that alarm call comprehension is socially learned during the juvenile stage, with comprehension preceding appropriate usage but no difference between learning their own or other species’ alarm calls. Significance statement Under natural conditions, animals do not just interact with members of their own species, but usually operate in a network of associated species. However, ontogenetic research on primate communication frequently ignores this significant element. We studied the development of con- and heterospecific alarm call recognition in wild sooty mangabeys. We found that communicative competence was acquired during the juvenile stages, with alarm call comprehension learning preceding appropriate vocal usage and with no clear difference in learning of con- and heterospecific signals. We also found that, during early stages of life, social referencing, a proactive form of social learning, was key in the acquisition of competent alarm call behaviour. Our results show that primates equally learn to interpret alarm calls from their own and other species during their early stages of life and that this learning process is refined as the animals mature.

Funding: This work was supported by a Royal Society Research Grant to SP (RG150108), Collaborative Research Grant funding by the Halle Institute for Global Research at Emory University and University of St Andrews to SP and AP, a Wellcome Trust Seed Award to SP (105621/Z/14/Z), a Emory Computational Neuroscience Fellowship stipend to OM, support from Emory University’s Graduate Division of Biological and Biomedical Sciences and from the George W. Woodruff Fellowship for LP, and VPASA Seed Grant funding at Georgia Gwinnett College awarded to CG. Sodium potassium ATPases (Na/K pumps) mediate long-lasting, dynamic cellular memories that can last tens of seconds. The mechanisms controlling the dynamics of this type of cellular memory are not well understood and can be counterintuitive. Here, we use computational modeling to examine how Na/K pumps and the ion concentration dynamics they influence shape cellular excitability. In a Drosophila larval motor neuron model, we incorporate a Na/K pump, a dynamic intracellular Na+ concentration, and a dynamic Na+ reversal potential. We probe neuronal excitability with a variety of stimuli, including step currents, ramp currents, and zap currents, then monitor the sub- and suprathreshold voltage responses on a range of time scales. We find that the interactions of a Na+-dependent pump current with a dynamic Na+ concentration and reversal potential endow the neuron with rich response properties that are absent when the role of the pump is reduced to the maintenance of constant ion concentration gradients. In particular, these dynamic pump-Na+ interactions contribute to spike rate adaptation and result in long-lasting excitability changes after spiking and even after sub-threshold voltage fluctuations on multiple time scales. We further show that modulation of pump properties can profoundly alter a neuron’s spontaneous activity and response to stimuli by providing a mechanism for bursting oscillations. Our work has implications for experimental studies and computational modeling of the role of Na/K pumps in neuronal activity, information processing in neural circuits, and the neural control of animal behavior. Publisher PDF

Funding: This work was supported by the Faraday Institution (grant number FIRG018). The authors would like to thank Dr David Rochester at Lancaster University for conducting the ICP-OES experiments. A.B.N. would like to acknowledge funding by the Engineering and Physical Sciences Research Council under grant numbers EP/L017008/1, EP/R023751/1 and EP/T019298/1 for the electron microscopy analysis. Sodium-ion batteries have attracted widespread interest due to the potential for providing safe and cheap energy storage. However, large scale use of Na-ion batteries is limited by insufficient performance from positive electrode materials, while also avoiding the use of expensive and toxic elements. Here, we present a bi-phasic sodium layered oxide material, O3/P2-Na0.75Mn0.35Fe0.35Ti0.1Al0.1Cu0.1O2, free of Li, Ni, and Co, which delivered high energy densities up to 420 Wh kg-1, discharge potential of 3.03 V, and high capacity retention of 80% over 70 cycles in half cells (292 Wh Kg-1 in full cells). Crucially, the high Na content is sufficient to provide high energy densities in full cell format. The intergrown nature of the material was confirmed by TEM and SAED analysis, while ex-situ XRD studies revealed the two phases undergo complementary c-parameter evolution, reducing overall volume change. These results demonstrate the potential for future commercialisation of bi-phasic materials utilising only Earth abundant elements. Publisher PDF

The authors would like to acknowledge the financial assistance of the UEA (CHE43.3.60), the EU Interreg Manche/Channel cross-border projects Innovative Synthesis: Chemistry and Entrepreneurship (IS:CE-chem: ref. 4061) and ‘Academy-Industry chemistry channel’ (AIcc: ref. 4196), Interreg, Ministry of Defence (R19648) and the EPSRC UK National Mass Spectrometry Facility at Swansea University. A unique, readily synthesised, upper-rim 1,3-difunctionalised calix[4]arene is reported; equipped with a fluorophore and an alkyne it mediates the efficient chemoselective detection of Au3+. Its ability to detect Au3+ is not perturbed by Au+ or excess competing and or contaminating metal e.g. platinum, cadmium, mercury, silver, sodium, magnesium or potassium cations. Publisher PDF

Funding: SERB-DST (Science and Engineering Research Board-Department of Science and Technology), Govt. of India, is duly acknowledged for financial assistance under Fast Track Scheme For Young Scientist (to Dr. Prabodh Chander Sharma) video file No.: SB/FT/CS-134/2012 dated: July 15, 2014. Cancer is one of the life-threatening diseases accountable for millions of demises globally. The inadequate effectiveness of the existing chemotherapy and its harmful effects has resulted in the necessity of developing innovative anticancer agents. Thiazolidin-4-one scaffold is among the most important chemical skeletons that illustrate anticancer activity. Thiazolidin-4-one derivatives have been the subject of extensive research and current scientific literature reveals that these compounds have shown significant anticancer activities. This manuscript is an earnest attempt to review novel thiazolidin-4-one derivatives demonstrating considerable potential as anticancer agents along with a brief discussion of medicinal chemistry-related aspects of these compounds and structural activity relationship studies in order to develop possible multi-target enzyme inhibitors. Most recently, various synthetic strategies have been developed by researchers to get various thiazolidin-4-one derivatives. In this review, the authors highlight the various synthetic, green, and nanomaterial-based synthesis routes of thiazolidin-4-ones as well as their role in anticancer activity by inhibition of various enzymes and cell lines. The detailed description of the existing modern standards in the field presented in this article may be interesting and beneficial to the scientists for further exploration of these heterocyclic compounds as possible anticancer agents. Publisher PDF

IntroductionThe ultimate deficit in amyotrophic lateral sclerosis (ALS) is neuromuscular junction (NMJ) loss, producing permanent paralysis, ultimately in respiratory muscles. However, understanding the functional and structural deficits at NMJs prior to this loss is crucial for therapeutic strategy design. Should early interventions focus on reversing denervation, or supporting largely intact NMJs that are functionally impaired? We therefore determined when functional and structural deficits appeared in diaphragmatic NMJs relative to the onset of hindlimb tremor (the first overt motor symptoms) in vivo in the SOD1-G93A mouse model of ALS.Materials and methodsWe employed electrophysiological recording of NMJ postsynaptic potentials for spontaneous and nerve stimulation-evoked responses. This was correlated with fluorescent imaging microscopy of the postsynaptic acetylcholine receptor (AChR) distribution throughout the postnatal developmental timecourse from 2 weeks to early symptomatic ages.ResultsSignificant reduction in the amplitudes of spontaneous miniature endplate potentials (mEPPs) and evoked EPPs emerged only at early symptomatic ages (in our colony, 18-22 weeks). Reductions in mEPP frequency, number of vesicles per EPP, and EPP rise time were seen earlier, at 16weeks, but this reversed by early symptomatic ages. However, the earliest and most striking impairment was an inability to maintain EPP amplitude during a 20 Hz stimulus train, which appeared 6 weeks before overt in vivo motor symptoms. Despite this, fluorescent α-bungarotoxin labelling revealed no systematic, progressive changes in 11 comprehensive NMJ morphological parameters (area, shape, compactness, number of acetylcholine receptor, AChR, regions, etc.) with disease progression. Rather, while NMJs were largely normally-shaped, from 16 weeks there was a progressive and substantial disruption in AChR concentration and distribution within the NMJ footprint.DiscussionThus, NMJ functional deficits appear at least 6 weeks before motor symptoms in vivo, while structural deficits occur 4 weeks later, and predominantly within NMJs. These data suggest initial therapies focused on rectifying suboptimal NMJ function could produce effective relief of symptoms of weakness.

This work was funded by a NERC Independent Research Fellowship (NE/K009370/1) and a Leverhulme Trust grant (RPG-2017-041 V) awarded to C.C.I. Of widespread interest in animal behavior and ecology is how animals search their environment for resources, and whether these search strategies are optimal. However, movement also affects predation risk through effects on encounter rates, the conspicuousness of prey, and the success of attacks. Here, we use predatory fish attacking a simulation of virtual prey to test whether predation risk is associated with movement behavior. Despite often being demonstrated to be a more efficient strategy for finding resources such as food, we find that prey displaying Lévy motion are twice as likely to be targeted by predators than prey utilizing Brownian motion. This can be explained by the predators, at the moment of the attack, preferentially targeting prey that were moving with straighter trajectories rather than prey that were turning more. Our results emphasize that costs of predation risk need to be considered alongside the foraging benefits when comparing different movement strategies. Publisher PDF

Funding: R.F. is supported by the Biological and Biotechnological Sciences Research Council. Magnesium (Mg2+) has many physiological functions within the body. These include important roles in maintaining cardiovascular functioning, where it contributes to the regulation of cardiac excitation–contraction coupling, endothelial functioning and haemostasis. The haemostatic roles of Mg2+ impact upon both the protein and cellular arms of coagulation. In this review, we examine how Mg2+ homeostasis is maintained within the body and highlight the various molecular roles attributed to Mg2+ in the cardiovascular system. In addition, we describe how nutritional and/or disease-associated magnesium deficiency, seen in some metabolic conditions, has the potential to influence cardiac and vascular outcomes. Finally, we also examine the potential for magnesium supplements to be employed in the prevention and treatment of cardiovascular disorders and in the management of cardiometabolic health. Publisher PDF

Funding: The St Andrews team would like to thank EPSRC (EP/P010482/1) and the Leverhulme Trust (RPG-2016-047) for financial support. Computational resources have been provided by the Consortium des Équipements de Calcul Intensif (CÉCI), funded by the Fonds de la Recherche Scientifiques de Belgique (F. R. S.-FNRS) under Grant no. 2.5020.11. Y. O. acknowledges funding by the Fonds de la Recherche Scientifique-FNRS under Grant no. F.4534.21 (MIS-IMAGINE). Two novel π-extended amine/carbonyl-based multi-resonance thermally activated delayed fluorescence (MR-TADF) emitters have been designed and synthesized. The two emitters are isomeric, composed of nine fused rings and show green-yellow emission. Sym-DiDiKTa and Asym-DiDiKTa possess tert-butyl groups distributed in a symmetrical and asymmetrical fashion, respectively, which significantly impact the single-crystal packing structure. The two compounds possess similar singlet–triplet energy gaps, ΔEST, of around 0.23 eV, narrowband emission characterized by a full-width at half-maximum, FWHM, of 29 nm and a photoluminescence quantum yield, ΦPL, of 70% and 53% for the symmetric and asymmetric counterparts, respectively, in toluene. Investigation in OLEDs demonstrated that the devices with Sym-DiDiKTa and Asym-DiDiKTa displayed electroluminescence maxima of 543 and 544 nm, and maximum external quantum efficiencies (EQEmax) of 9.8% and 10.5%, respectively. The maximum EQE was further improved to 19.9% by employing a hyperfluorescence strategy. We further present the first example of a neutral MR-TADF emitter incorporated in a LEC device where Sym-DiDiKTa acts as the emitter. The LEC shows a λEL at 551 nm and FWHM of 60 nm with luminance of 300 cd m−2 and a fast turn-on time of less than 2 s to 100 cd m−2. Publisher PDF

Funding: China Scholarship Council - 2019 06250199, 2020 06250026; Engineering and Physical Sciences Research Council - EP/L017008, EP/P010482/1. Multiresonant thermally activated delayed fluorescence (MR-TADF) compounds are attractive as emitters for organic light-emitting diodes (OLEDs) as they can simultaneously harvest both singlet and triplet excitons to produce light in the device and show very narrow emission spectra, which translates to excellent color purity. Here, we report the first example of an MR-TADF emitter (DOBDiKTa) that fuses together fragments from the two major classes of MR-TADF compounds, those containing boron (DOBNA) and those containing carbonyl groups (DiKTa) as acceptor fragments in the MR-TADF skeleton. The resulting molecular design, this compound shows desirable narrowband pure blue emission and efficient TADF character. The co-host OLED with DOBDiKTa as the emitter showed a maximum external quantum efficiency (EQEmax) of 17.4 %, an efficiency roll-off of 32 % at 100 cd m−2, and Commission Internationale de l’Éclairage (CIE) coordinates of (0.14, 0.12). Compared to DOBNA and DiKTa, DOBDiKTa shows higher device efficiency with reduced efficiency roll-off while maintaining a high color purity, which demonstrates the promise of the proposed molecular design. Publisher PDF

Funding: UK Engineering and Physical Sciences Research Council - EP/S019359/1; China Scholarship Council. The isothiourea-catalyzed regio- and enantioselective formal [2 + 2] cycloaddition of C(1)-alkyl and C(1)-unsubstituted ammonium enolates with β- and α,β-substituted trifluoromethylenones has been developed. In all cases, preferential [2 + 2]-cycloaddition over the alternative [4 + 2]-cycloaddition is observed, giving β-lactones with excellent diastereo- and enantioselectivity (34 examples, up to >95:5 dr, >99:1 er). The regioselectivity of the process was dictated by the nature of the substituents on both reaction components. Solely [2 + 2] cycloaddition products are observed when using α,β-substituted trifluoromethylenones or α-trialkylsilyl acetic acid derivatives; both [2 + 2] and [4 + 2] cycloaddition products are observed when using β-substituted trifluoromethylenones and α-alkyl-α-trialkylsilyl acetic acids as reactants, with the [2 + 2] cycloaddition as the major reaction product. The beneficial role of the α-silyl substituent within the acid component in this protocol has been demonstrated by control experiments. Publisher PDF

Contactin-associated protein-like 2 (CNTNAP2) gene encodes for CASPR2, a presynaptic type 1 transmembrane protein, involved in cell–cell adhesion and synaptic interactions. Biallelic CNTNAP2 loss has been associated with “Pitt-Hopkins-like syndrome-1” (MIM#610042), while the pathogenic role of heterozygous variants remains controversial. We report 22 novel patients harboring mono- (n = 2) and bi-allelic (n = 20) CNTNAP2 variants and carried out a literature review to characterize the genotype–phenotype correlation. Patients (M:F 14:8) were aged between 3 and 19 years and affected by global developmental delay (GDD) (n = 21), moderate to profound intellectual disability (n = 17) and epilepsy (n = 21). Seizures mainly started in the first two years of life (median 22.5 months). Antiseizure medications were successful in controlling the seizures in about two-thirds of the patients. Autism spectrum disorder (ASD) and/or other neuropsychiatric comorbidities were present in nine patients (40.9%). Nonspecific midline brain anomalies were noted in most patients while focal signal abnormalities in the temporal lobes were noted in three subjects. Genotype–phenotype correlation was performed by also including 50 previously published patients (15 mono- and 35 bi-allelic variants). Overall, GDD (p p p = 0.012), ASD (p = 0.009), language impairment (p = 0.020) and severe cognitive impairment (p = 0.031) were significantly associated with the presence of biallelic versus monoallelic variants. We have defined the main features associated with biallelic CNTNAP2 variants, as severe cognitive impairment, epilepsy and behavioral abnormalities. We propose CASPR2-deficiency neurodevelopmental disorder as an exclusively recessive disease while the contribution of heterozygous variants is less likely to follow an autosomal dominant inheritance pattern.

This project received funding from the European Union's 8th Framework Programme, Horizon 2020 (grant agreement number: 802719) and the St Andrews Restarting Research Funding Scheme (2020). 1. Studying animal behaviour allows us to understand how different species and individuals navigate their physical and social worlds. Video coding of behaviour is considered a gold standard: allowing researchers to extract rich nuanced behavioural datasets, validate their reliability, and for research to be replicated. However, in practice, videos are only useful if data can be efficiently extracted. Manually locating relevant footage in 10,000 s of hours is extremely time-consuming, as is the manual coding of animal behaviour, which requires extensive training to achieve reliability. 2. Machine learning approaches are used to automate the recognition of patterns within data, considerably reducing the time taken to extract data and improving reliability. However, tracking visual information to recognise nuanced behaviour is a challenging problem and, to date, the tracking and pose-estimation tools used to detect behaviour are typically applied where the visual environment is highly controlled. 3. Animal behaviour researchers are interested in applying these tools to the study of wild animals, but it is not clear to what extent doing so is currently possible, or which tools are most suited to particular problems. To address this gap in knowledge, we describe the new tools available in this rapidly evolving landscape, suggest guidance for tool selection, provide a worked demonstration of the use of machine learning to track movement in video data of wild apes, and make our base models available for use. 4. We use a pose-estimation tool, DeepLabCut, to demonstrate successful training of two pilot models of an extremely challenging pose estimate and tracking problem: multi-animal wild forest-living chimpanzees and bonobos across behavioural contexts from hand-held video footage. 5. With DeepWild we show that, without requiring specific expertise in machine learning, pose estimation and movement tracking of free-living wild primates in visually complex environments is an attainable goal for behavioural researchers. Publisher PDF

Funding: For the purpose of open access, the authors have applied a Creative Commons Attribution (CC BY) licence to any Accepted Author Manuscript version arising. The authors thank the StAnD (St Andrews and Dundee) EPR group for long-standing support and in particular Dr El Mkami for assistance with PDS experiments. J. L.W. acknowledges support by the BBSRC DTP Eastbio (BB/M010996/1). A. G. acknowledges the EPSRC-funded Centre for Doctoral Training in ‘integrated magnetic resonance’, iMR-CDT (EP/J500045/1) B. E. B. and K. A. acknowledge support by the Leverhulme Trust (RPG-2018-397). B. E. B. acknowledges equipment funding by BBSRC (BB/R013780/1 and BB/T017740/1). Pulse dipolar spectroscopy (PDS) measurements are an important complementary tool in structural biology and are increasingly applied to macromolecular assemblies implicated in human health and disease at physiological concentrations. This requires ever higher sensitivity, and recent advances have driven PDS measurements into the mid-nanomolar concentration regime, though optimization and acquisition of such measurements remains experimentally demanding and time expensive. One important consideration is that constant-time acquisition represents a hard limit for measurement sensitivity, depending on the maximum measured distance. Determining this distance a priori has been facilitated by machine-learning structure prediction (AlphaFold2 and RoseTTAFold) but is often confounded by non-representative behaviour in frozen solution that may mandate multiple rounds of optimization and acquisition. Herein, we endeavour to simultaneously enhance sensitivity and streamline PDS measurement optimization to one-step by benchmarking a variable-time acquisition RIDME experiment applied to CuII-nitroxide and CuII-CuII model systems. Results demonstrate marked sensitivity improvements of both 5- and 6-pulse variable-time RIDME of between 2- and 5-fold over the constant-time analogues. Publisher PDF

Funding: Horizon 2020 Framework Programme - 838885; Leverhulme Trust - RPG-2016-047; Engineering and Physical Sciences Research Council - EP/L017008, EP/P010482/1; Fonds de la Recherche Scientifiques de Belgique - 2.5020.11; Walloon Region - n1117545; Fonds De La Recherche Scientifique - FNRS - F.4534.21. Two multiresonant thermally activated delayed fluorescence (MR-TADF) emitters are presented and it is shown how further borylation of a deep-blue MR-TADF emitter, DIDOBNA-N, both blueshifts and narrows the emission producing a new near-UV MR-TADF emitter, MesB-DIDOBNA-N, are shown. DIDOBNA-N emits bright blue light (ΦPL = 444 nm, FWHM = 64 nm, ΦPL = 81%, τd = 23 ms, 1.5 wt% in TSPO1). The deep-blue organic light-emitting diode (OLED) based on this twisted MR-TADF compound shows a very high maximum external quantum efficiency (EQEmax) of 15.3% for a device with CIEy of 0.073. The fused planar MR-TADF emitter, MesB-DIDOBNA-N shows efficient and narrowband near-UV emission (λPL = 402 nm, FWHM = 19 nm, ΦPL = 74.7%, τd = 133 ms, 1.5 wt% in TSPO1). The best OLED with MesB-DIDOBNA-N, doped in a co-host, shows the highest efficiency reported for a near-UV OLED at 16.2%. With a CIEy coordinate of 0.049, this device also shows the bluest EL reported for a MR-TADF OLED to date. Publisher PDF

Funding: This work was supported by the Swiss National Science Foundation (PP00P3_163850 & PP00P3_198912) to S.W.T. and the NCCR Evolving Language (SNSF Agreement #51NF40_180888). Through syntax, i.e., the combination of words into larger phrases, language can express a limitless number of messages. Data in great apes, our closest-living relatives, are central to the reconstruction of syntax’s phylogenetic origins, yet are currently lacking. Here, we provide evidence for syntactic-like structuring in chimpanzee communication. Chimpanzees produce “alarm-huus” when surprised and “waa-barks” when potentially recruiting conspecifics during aggression or hunting. Anecdotal data suggested chimpanzees combine these calls specifically when encountering snakes. Using snake presentations, we confirm call combinations are produced when individuals encounter snakes and find that more individuals join the caller after hearing the combination. To test the meaning-bearing nature of the call combination, we use playbacks of artificially-constructed call combinations and both independent calls. Chimpanzees react most strongly to call combinations, showing longer looking responses, compared with both independent calls. We propose the “alarm-huu + waa-bark” represents a compositional syntactic-like structure, where the meaning of the call combination is derived from the meaning of its parts. Our work suggests that compositional structures may not have evolved de novo in the human lineage, but that the cognitive building-blocks facilitating syntax may have been present in our last common ancestor with chimpanzees. Publisher PDF

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This work was supported in part by the Netherlands Forensic Institute, Netherlands Genomics Initiative/Netherlands Organization for Scientific Research within the framework of the Forensic Genomics Consortium Netherlands, the 6th Framework project EUCLOCK (018741), and UK Biotechnology and Biological Sciences Research Council Grant BB/I019405/1. Additional funding was received from the Cancer Research UK Cancer Therapeutics Unit award (Ref: C2739/A22897) and a Cancer Therapeutics Centre award (Ref: C309/A25144 to FR), the NWO-STW Perspective Program grant ‘OnTime’ (project 12185 to TW and RAH). Circadian rhythms influence physiology, metabolism, and molecular processes in the human body. Estimation of individual body time (circadian phase) is therefore highly relevant for individual optimization of behavior (sleep, meals, sports), diagnostic sampling, medical treatment, and for treatment of circadian rhythm disorders. Here, we provide a partial least squares regression (PLSR) machine learning approach that uses plasma-derived metabolomics data in one or more samples to estimate dim light melatonin onset (DLMO) as a proxy for circadian phase of the human body. For this purpose, our protocol was aimed to stay close to real-life conditions. We found that a metabolomics approach optimized for either women or men under entrained conditions performed equally well or better than existing approaches using more labor-intensive RNA sequencing-based methods. Although estimation of circadian body time using blood-targeted metabolomics requires further validation in shift work and other real-world conditions, it currently may offer a robust, feasible technique with relatively high accuracy to aid personalized optimization of behavior and clinical treatment after appropriate validation in patient populations. Publisher PDF