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Continents are formed by the amalgamation of numerous micro-terranes and island arcs, so they have spatially varying lithosphere strengths. The crème brûlée (CB) model and the jelly sandwich (JS) model have been commonly used to describe continental lithosphere strength–depth variations. Depending on the strength of the continental lower crust, the CB and JS models can be further subdivided into two subclasses in which the I subclass (CB-I and JS-I) and II subclass (CB-II and JS-II), respectively, have a strong or weak lower crust. During the continental collision, lithosphere deformation is the byproduct of the comprehensive interaction of multiple terranes. Here we used 2-D thermomechanical numerical models that contain three continental terranes to systematically explore the effects of terranes with various strengths on continental deformation and studied the effects of different rheological assumptions on terrane deformation. We found four types of lithosphere deformation patterns: collision, subduction, thickening and delamination, and replacement. These simulation patterns are seen in observed deformation patterns and structures in East Asia, suggesting they are likely to be naturally occurring modes of intracontinental orogenesis.

The acoustic repertoires of long-finned pilot whales (Globicephala melas) in the Mediterranean Sea are poorly understood. This study aims to create a catalogue of calls, analyse acoustic parameters, and propose a classification tree for future research. An acoustic database was compiled using recordings from the Alboran Sea, Gulf of Lion and Ligurian Sea (Western Mediterranean Basin) between 2008 and 2022, totalling 640 calls. Using a deep neural network, the calls were clustered based on frequency contour similarities, leading to the identification of 40 distinct call types defining the local population’s vocal repertoire. These categories encompass pulsed calls with varied complexities, from simplistic to highly intricate structures comprising multiple elements and segments. This study marks the initial documentation of the vocal catalogue of long-finned pilot whales in the Mediterranean Sea. Subsequent research should delve deeper into this multifaceted communication system and explore its potential linkages with social structures.

We report X-ray resonant magnetic scattering studies of a Permalloy artificial square ice nanomagnet array, focussing on the field-driven evolution of the sum Σ and difference Δ signals of left and right handed circularly polarized synchrotron X-rays at different lateral positions in reciprocal space Qx. We used X-rays tuned to the Fe L3 resonance energy, with the scattering plane aligned along a principal symmetry axis of the array. Details of the specular Δ hysteresis curve are discussed, following the system magnetization from an initial demagnetized state. The periodic structure gives rise to distinct peaks at in-plane reciprocal Bragg positions, as shown by fitting Σ(Qx) to a model based on a simple unit cell structure. Diffraction order-dependent hysteresis in Δ is observed, indicative of the reordering of magnetization on the system's two interpenetrating sublattices, which markedly deviates from an ideal Ising picture under strong applied fields.

The maintenance of cross-cultural variation and arbitrary traditions in human populations is a key question in cultural evolution. Conformist transmission, the tendency to follow the majority, was previously considered central to this phenomenon. However, recent theory indicates that cognitive biases can greatly reduce its ability to maintain traditions. Therefore, we expanded prior models to investigate two other ways that cultural variation can be sustained: payoff-biased transmission and norm reinforcement. Our findings predict that both payoff-biased transmission and reinforcement can enhance conformist transmission's ability to maintain traditions. However, payoff-biased transmission can only sustain cultural variation if it is functionally related to environmental factors. In contrast, norm reinforcement readily generates and maintains arbitrary cultural variation. Furthermore, reinforcement results in path-dependent cultural dynamics, meaning that historical traditions influence current practices, even though group behaviours have changed. We conclude that environmental variation probably plays a role in functional cultural traditions, but arbitrary cultural variation is more plausibly due to the reinforcement of norm compliance.

Gas isotope thermometry using the isotopes of molecular nitrogen and argon has been used extensively to reconstruct past surface temperature change from Greenland ice cores. The gas isotope ratios δ15N and δ40Ar in the ice core are each set by the amount of gravitational and thermal fractionation in the firn. The gravitational component of fractionation is proportional to the firn thickness, and the thermal component is proportional to the temperature difference between the top and bottom of the firn column, which can be related to surface temperature change. Compared to Greenland, Antarctic climate change is typically more gradual and smaller in magnitude, which results in smaller thermal fractionation signals that are harder to detect. This has hampered application of gas isotope thermometry to Antarctic ice cores. Here, we present an analytical method for measuring δ15N and δ40Ar with a precision of 0.002 ‰ per atomic mass unit, a two-fold improvement on previous work. This allows us to reconstruct changes in firn thickness and temperature difference at the South Pole between 30 and 5 kyr BP. We find that variability in firn thickness is controlled in part by changes in snow accumulation rate, which is, in turn, influenced strongly by the along-flowline topography upstream of the ice core site. Variability in our firn temperature difference record cannot be explained by annual-mean processes. We therefore propose that the ice core gas isotopes contain a seasonal bias due to rectification of seasonal signals in the upper firn. The strength of the rectification also appears to be linked to fluctuations in the upstream topography. As further evidence for the existence of rectification, we present new data from the Dome Fuji ice core that are also consistent with a seasonal bias throughout the Holocene. Our findings have important implications for the interpretation of ice core gas records. For example, we show that the effects of upstream topography on ice core records can be significant at flank sites like the South Pole – they are responsible for some of the largest signals in our record. Presumably upstream signals impact other flank-flow ice cores such as EDML, Vostok, and EGRIP similarly. Additionally, future work is required to confirm the existence of seasonal rectification in polar firn, to determine how spatially and temporally widespread rectifier effects are, and to incorporate the relevant physics into firn air models.

The variations of δO2/N2 and δAr/N2 in the Dome Fuji ice core were measured from 112 m (bubbly ice) to 2001 m (clathrate hydrate ice). Our method, combined with the low storage temperature of the samples (−50 ∘C), successfully excludes post-coring gas-loss fractionation signals from our data. From the bubbly ice to the middle of the bubble–clathrate transition zone (BCTZ) (112–800 m) and below the BCTZ (>1200 m), the δO2/N2 and δAr/N2 data exhibit orbital-scale variations similar to local summer insolation. The data in the lower BCTZ (800–1200 m) have large scatter, which may be caused by millimeter-scale inhomogeneity of air composition combined with finite sample lengths. The insolation signal originally recorded at the bubble close-off remains through the BCTZ, and the insolation signal may be reconstructed by analyzing long ice samples (more than 50 cm for the Dome Fuji core). In the clathrate hydrate zone, the scatter around the orbital-scale variability decreases with depth, indicating diffusive smoothing of δO2/N2 and δAr/N2. A simple gas diffusion model was used to reproduce the smoothing and thus constrain their permeation coefficients. The relationship between δAr/N2 and δO2/N2 is markedly different for the datasets representing bubble close-off (slope ∼ 0.5), bubble–clathrate hydrate transformation (∼1), and post-coring gas loss (∼0.2), suggesting that the contributions of the mass-independent and mass-dependent fractionation processes are different for those cases. The method and data presented here may be useful for improving the orbital dating of deep ice cores over the multiple glacial cycles and further studying non-insolation-driven signals (e.g., atmospheric composition) of these gases.

Abstract The generalized abundance index (GAI) provides a useful tool for estimating relative population sizes and trends of seasonal invertebrates from species' count data and offers potential for inferring which external factors may influence phenology and demography through parametric descriptions of seasonal variation. We provide an R package that extends previous software with the ability to include covariates when fitting parametric GAI models, where seasonal variation is described by either a mixture of Normal distributions or a stopover model which provides estimates of life span. The package also generalizes the models to allow any number of broods/generations in the target population within a defined season. The option to perform bootstrapping, either parametrically or nonparametrically, is also provided. The new package allows models to be far more flexible when describing seasonal variation, which may be dependent on site‐specific environmental factors or consist of many broods/generations which may overlap, as demonstrated by two case studies. Our open‐source software, available at https://github.com/calliste‐fagard‐jenkin/rGAI, makes these extensions widely and freely available, allowing the complexity of GAI models used by ecologists and applied statisticians to increase accordingly.

Abstract Prestige-biased social learning occurs when individuals preferentially learn from others who are highly respected, admired, copied, or attended to in their group. This form of social learning is argued to reflect novel forms of social hierarchy in human societies, and, by providing an efficient short-cut to acquiring adaptive information, underpin the cumulative cultural evolution that has contributed to our species’ ecological success. Despite these potentially important consequences, little empirical work to date has tested the basic predictions of prestige-biased social learning. Here we provide evidence supporting the key predictions that prestige-biased social learning is used when it constitutes an indirect cue of success, and when success-biased social learning is unavailable. We ran an online experiment (n = 269) in which participants could copy each other in real-time to score points on a general-knowledge quiz. Our implementation of ‘prestige’ was the number of times someone had previously been copied by others. Importantly, prestige was an emergent property of participants’ behaviour during the experiment; no deception or manipulation of prestige was employed at any time. We found that, as predicted, participants used prestige-biased social learning when the prestige cue was an indirect cue of success, and when direct success information was unavailable. This highlights how people flexibly and adaptively employ social learning strategies based on the reliability of the information that such strategies provide.

The authors here present a 3D model that simulates the formation of the Chicxulub impact crater. Based on asymmetries in the subsurface structure of the Chicxulub crater, the authors diagnose impact angle and direction and suggest a steeply inclined (60° to horizontal) impact from the northeast.

Background: The therapeutic benefits of ketamine have been demonstrated for a variety of psychiatric disorders. However, the role of ketamine induced psychoactive experiences in mediating the therapeutic effects is unclear. Despite the growing quantitative research on the efficacy of ketamine treatment, very few studies examined participant experiences of ketamine infusions in a treatment setting.Aims: The current study aimed to examine participant experiences of ketamine infusions and how these relate to therapeutic mechanisms in a clinical trial setting.Methods: We conducted semi-structured interviews with 12 participants who received up to three ketamine infusions (0.8 mg/kg) as part of a Phase II double blind, randomised controlled trial. The interviews explored participants' acute experiences of ketamine infusions, experiences of psychotherapy/education, and the lasting effects of the trial. The interviews were transcribed verbatim and analysed using thematic analysis.Results: Six key themes were identified. (1) Participants reported multifaceted motivations for trial participation. (2) The set and setting was found to be influential in determining acute ketamine experiences. The acute ketamine experiences included: (3) the inherent contradictions of the experience (e.g., dissociation vs feelings of connection), (4) rapidly fluctuating and changing experiences, (5) meaningful, mystical and spiritual experiences. Finally, the final theme (6) relates to the transformational effects of the infusions and the trial.Conclusion: Provided in a supportive and professional environment, ketamine treatment led to a significant change in relationship with alcohol. Ketamine induced ego dissolution and dissociation were reported to be related to the transformational effects on relationship with alcohol. The extent to which the acute psychoactive effects of ketamine mediate therapeutic effects on drinking outcomes remain to be investigated in the trial data. The acute effects of ketamine reported by our participants transcend its traditional conceptualisation as a “dissociative anaesthetic”; therefore, we suggest the development or use of new measures alongside ketamine infusions to fully capture the spectrum of these effects which may be crucial in its therapeutic and transformative effects.

Abstract Background Repeated outbreaks of emerging pathogens underscore the need for preparedness plans to prevent, detect, and respond. As countries develop and improve National Action Plans for Health Security, addressing subnational variation in preparedness is increasingly important. One facet of preparedness and mitigating disease transmission is health facility accessibility, linking infected persons with health systems and vice versa. Where potential patients can access care, local facilities must ensure they can appropriately diagnose, treat, and contain disease spread to prevent secondary transmission; where patients cannot readily access facilities, alternate plans must be developed. Here, we use travel time to link facilities and populations at risk of viral hemorrhagic fevers (VHFs) and identify spatial variation in these respective preparedness demands. Methods and findings We used geospatial resources of travel friction, pathogen environmental suitability, and health facilities to determine facility accessibility of any at-risk location within a country. We considered in-country and cross-border movements of exposed populations and highlighted vulnerable populations where current facilities are inaccessible and new infrastructure would reduce travel times. We developed profiles for 43 African countries. Resulting maps demonstrate gaps in health facility accessibility and highlight facilities closest to areas at risk for VHF spillover. For instance, in the Central African Republic, we identified travel times of over 24 h to access a health facility. Some countries had more uniformly short travel times, such as Nigeria, although regional disparities exist. For some populations, including many in Botswana, access to areas at risk for VHF nationally was low but proximity to suitable spillover areas in bordering countries was high. Additional analyses provide insights for considering future resource allocation. We provide a contemporary use case for these analyses for the ongoing Ebola outbreak. Conclusions These maps demonstrate the use of geospatial analytics for subnational preparedness, identifying facilities close to at-risk populations for prioritizing readiness to detect, treat, and respond to cases and highlighting where gaps in health facility accessibility exist. We identified cross-border threats for VHF exposure and demonstrate an opportunity to improve preparedness activities through the use of precision public health methods and data-driven insights for resource allocation as part of a country’s preparedness plans.

Context: Bauhinia L. species, including Bauhinia holophylla (Bong.) Steud. (Fabaceae), have traditionally been used to treat diabetes. Bauhinia is a complex botanical genus, and the indiscriminate use of the diverse Bauhinia species is reflected in the experimental divergence of their medicinal potential. Objective: The hypoglycaemic and hypolipidaemic effects, molecular mechanism of action and phytochemical properties of an authentic extract of B. holophylla leaves were evaluated. Materials and methods: A phytochemical study of a 70% EtOH extract was performed using FIA-ESI-IT-MS/MSn and HPLC-PAD-ESI-IT-MS. The extract (200 or 400 mg/kg b.w.) was administered for 14 days to streptozotocin-induced diabetic Swiss mice. Glucose tolerance and insulin sensitivity, blood parameters, gene and protein expression, and the in vivo and in vitro inhibition of intestinal glucosidases were assessed. Results: HPLC-PAD-ESI-IT-MS analysis identified flavonoid derivatives of quercetin, myricetin, luteolin and kaempferol. Treatment with 400 mg/kg of the extract reduced blood glucose (269.0 ± 32.4 mg/dL vs. 468.0 ± 32.2 mg/dL for diabetic animals), improved glucose tolerance, decreased cholesterol and triglyceride levels, and increased the mRNA expression of proteins involved in glucogenesis in the liver and muscle, such as PI3-K/Akt, GS, GSK3-β (ser-9), AMPK and Glut4. The activity of intestinal maltase was inhibited in vitro (IC50: 43.0 µg/mL for the extract compared to 516.4 µg/mL for acarbose) and in vivo. Discussion and conclusions: Treatment with B. holophylla was associated with a marked hypoglycaemic effect through the stimulation of glycogenesis and inhibition of gluconeogenesis and intestinal glucose absorption, without increasing basal insulinaemia.

Ayahuasca is a natural psychoactive brew, used in traditional ceremonies in the Amazon basin. Recent research has indicated that ayahuasca is pharmacologically safe and its use may be positively associated with improvements in psychiatric symptoms. The mechanistic effects of ayahuasca are yet to be fully established. In this prospective naturalistic study, 63 self-selected participants took part in ayahuasca ceremonies at a retreat centre in the Peruvian Amazon. Participants undertook the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), Self-compassion Scale (SCS), Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), as well as secondary measures, pre- and post-retreat and at 6-months. Participants also provided saliva samples for pre/post epigenetic analysis. Overall, a statistically significant decrease in BDI-II (13.9 vs. 6.1, p < 0.001), STAI (44.4 vs. 34.3 p < 0.001) scores, and CORE-OM scores were observed (37.3 vs. 22.3 p < 0.001) at post-retreat, as well as a concurrent increase in SCS (3.1 vs. 3.6, p < 0.001). Psychometric improvements were sustained, and on some measures values further decreased at 6-month follow-up, suggesting a potential for lasting therapeutic effects. Changes in memory valence were linked to the observed psychometric improvements. Epigenetic findings were equivocal, but indicated that further research in candidate genes, such as sigma non-opioid intracellular receptor 1 (SIGMAR1), is warranted. This data adds to the literature supporting ayahuasca's possible positive impact on mental health when conducted in a ceremonial context. Further investigation into clinical samples, as well as greater analyses into the mechanistic action of ayahuasca is advised.

Prestige-biased social learning (henceforth “prestige-bias”) occurs when individuals predominantly choose to learn from a prestigious member of their group, i.e. someone who has gained attention, respect and admiration for their success in some domain. Prestige-bias is proposed as an adaptive social-learning strategy as it provides a short-cut to identifying successful group members, without having to assess each person’s success individually. Previous work has documented prestige-bias and verified that it is used adaptively. However, the domain-specificity and generality of prestige-bias has not yet been explicitly addressed experimentally. By domain-specific prestige-bias we mean that individuals choose to learn from a prestigious model only within the domain of expertise in which the model acquired their prestige. By domain-general prestige-bias we mean that individuals choose to learn from prestigious models in general, regardless of the domain in which their prestige was earned. To distinguish between domain specific and domain general prestige we ran an online experiment (n = 397) in which participants could copy each other to score points on a general-knowledge quiz with varying topics (domains). Prestige in our task was an emergent property of participants’ copying behaviour. We found participants overwhelmingly preferred domain-specific (same topic) prestige cues to domain-general (across topic) prestige cues. However, when only domain-general or cross-domain (different topic) cues were available, participants overwhelmingly favoured domain-general cues. Finally, when given the choice between cross-domain prestige cues and randomly generated Player IDs, participants favoured cross-domain prestige cues. These results suggest participants were sensitive to the source of prestige, and that they preferred domain-specific cues even though these cues were based on fewer samples (being calculated from one topic) than the domain-general cues (being calculated from all topics). We suggest that the extent to which people employ a domain-specific or domain-general prestige-bias may depend on their experience and understanding of the relationships between domains.

Abstract An expanded sedimentary section provides an opportunity to elucidate conditions in the nascent Chicxulub crater during the hours to millennia after the Cretaceous‐Paleogene (K‐Pg) boundary impact. The sediments were deposited by tsunami followed by seiche waves as energy in the crater declined, culminating in a thin hemipelagic marlstone unit that contains atmospheric fallout. Seiche deposits are predominantly composed of calcite formed by decarbonation of the target limestone during impact followed by carbonation in the water column. Temperatures recorded by clumped isotopes of these carbonates are in excess of 70°C, with heat likely derived from the central impact melt pool. Yet, despite the turbidity and heat, waters within the nascent crater basin soon became a viable habitat for a remarkably diverse cross section of the food chain. The earliest seiche layers deposited with days or weeks of the impact contain earliest Danian nannoplankton and dinocyst survivors. The hemipelagic marlstone representing the subsequent years to a few millennia contains a nearly monogeneric calcareous dinoflagellate resting cyst assemblage suggesting deteriorating environmental conditions, with one interpretation involving low light levels in the impact aftermath. At the same horizon, microbial fossils indicate a thriving bacterial community and unique phosphatic fossils including appendages of pelagic crustaceans, coprolites and bacteria‐tunneled fish bone, suggesting that this rapid recovery of the base of the food chain may have supported the survival of larger, higher trophic‐level organisms. The extraordinarily diverse fossil assemblage indicates that the crater was a unique habitat in the immediate impact aftermath, possibly as a result of heat and nutrients supplied by hydrothermal activity.

Abstract Women appear to copy other women’s preferences for men’s faces. This ‘mate-choice copying’ is often taken as evidence of psychological adaptations for processing social information related to mate choice, for which facial information is assumed to be particularly salient. No experiment, however, has directly investigated whether women preferentially copy each other’s face preferences more than other preferences. Further, because prior experimental studies used artificial social information, the effect of real social information on attractiveness preferences is unknown. We collected attractiveness ratings of pictures of men’s faces, men’s hands, and abstract art given by heterosexual women, before and after they saw genuine social information gathered in real time from their peers. Ratings of faces were influenced by social information, but no more or less than were images of hands and abstract art. Our results suggest that evidence for domain-specific social learning mechanisms in humans is weaker than previously suggested.

Human cooperation, occurring without reciprocation and between unrelated individuals in large populations, represents an evolutionary puzzle. One potential explanation is that cooperative behaviour may be transmitted between individuals via social learning. Using an online social dilemma experiment, we find evidence that participants’ contributions were more consistent with payoff-biased transmission than prestige-biased transmission or conformity. We also found some evidence for lower cooperation (i) when exposed to social information about peer cooperation levels than without such information, and (ii) in the prisoners’ dilemma game compared to the snowdrift game. A simulation model established that the observed cooperation was more likely to be caused by participants’ general propensity to cooperate than by the effect of social learning strategies employed within the experiment, but that this cooperative propensity could be reduced through selection. Overall, our results support previous experimental evidence indicating the role of payoff-biased transmission in explaining cooperative behaviour, but we find that this effect was small and was overwhelmed by participants’ general propensity for cooperation.

Abstract Alcohol is known to facilitate memory if given after learning information in the laboratory; we aimed to investigate whether this effect can be found when alcohol is consumed in a naturalistic setting. Eighty-eight social drinkers were randomly allocated to either an alcohol self-dosing or a sober condition. The study assessed both retrograde facilitation and alcohol induced memory impairment using two independent tasks. In the retrograde task, participants learnt information in their own homes, and then consumed alcohol ad libitum. Participants then undertook an anterograde memory task of alcohol impairment when intoxicated. Both memory tasks were completed again the following day. Mean amount of alcohol consumed was 82.59 grams over the evening. For the retrograde task, as predicted, both conditions exhibited similar performance on the memory task immediately following learning (before intoxication) yet performance was better when tested the morning after encoding in the alcohol condition only. The anterograde task did not reveal significant differences in memory performance post-drinking. Units of alcohol drunk were positively correlated with the amount of retrograde facilitation the following morning. These findings demonstrate the retrograde facilitation effect in a naturalistic setting, and found it to be related to the self-administered grams of alcohol.

Cultural evolution is the product of the psychological mechanisms that underlie individual decision making. One commonly studied learning mechanism is a disproportionate preference for majority opinions, known as conformist transmission. While most theoretical and experimental work approaches the majority in terms of the number of individuals that perform a behaviour or hold a belief, some recent experimental studies approach the majority in terms of the number of instances a behaviour is performed. Here, we use a mathematical model to show that disagreement between these two notions of the majority can arise when behavioural variants are performed at different rates, with different salience or in different contexts (variant overrepresentation) and when a subset of the population act as demonstrators to the whole population (model biases). We also show that because conformist transmission changes the distribution of behaviours in a population, how observers approach the majority can cause populations to diverge, and that this can happen even when the two approaches to the majority agree with regards to which behaviour is in the majority. We discuss these results in light of existing findings, ranging from political extremism on twitter to studies of animal foraging behaviour. We conclude that the factors we considered (variant overrepresentation and model biases) are plausibly widespread. As such, it is important to understand how individuals approach the majority in order to understand the effects of majority influence in cultural evolution.

The biologically active lipopeptide kalkitoxin was previously isolated from the marine cyanobacterium Moorea producens (Lyngbya majuscula). Kalkitoxin exhibited N-methyl-d-aspartate (NMDA)-mediated neurotoxicity and acted as an inhibitory ligand for voltage-sensitive sodium channels in cultured rat cerebellar granule neurons. Subsequent studies revealed that kalkitoxin generated a delayed form of colon tumor cell cytotoxicity in 7-day clonogenic cell survival assays. Cell line- and exposure time-dependent cytostatic/cytotoxic effects were previously observed with mitochondria-targeted inhibitors of hypoxia-inducible factor-1 (HIF-1). The transcription factor HIF-1 functions as a key regulator of oxygen homeostasis. Therefore, we investigated the ability of kalkitoxin to inhibit hypoxic signaling in human tumor cell lines. Kalkitoxin potently and selectively inhibited hypoxia-induced activation of HIF-1 in T47D breast tumor cells (IC50 5.6 nM). Mechanistic studies revealed that kalkitoxin inhibits HIF-1 activation by suppressing mitochondrial oxygen consumption at electron transport chain (ETC) complex I (NADH-ubiquinone oxidoreductase). Further studies indicate that kalkitoxin targets tumor angiogenesis by blocking the induction of angiogenic factors (i.e., VEGF) in tumor cells.

Invasive arthropods pose unique management challenges in various environments, the first of which is correct identification. This apparently mundane task is particularly difficult if multiple species are morphologically indistinguishable but accurate identification can be determined with DNA barcoding provided an adequate reference set is available. Scirtothrips dorsalis is a highly polyphagous plant pest with a rapidly expanding global distribution and this species, as currently recognized, may be comprised of cryptic species. Here we report the development of a comprehensive DNA barcode library for S. dorsalis and seven nuclear markers via next-generation sequencing for identification use within the complex. We also report the delimitation of nine cryptic species and two morphologically distinguishable species comprising the S. dorsalis species complex using histogram analysis of DNA barcodes, Bayesian phylogenetics, and the multi-species coalescent. One member of the complex, here designated the South Asia 1 cryptic species, is highly invasive, polyphagous, and likely the species implicated in tospovirus transmission. Two other species, South Asia 2, and East Asia 1 are also highly polyphagous and appear to be at an earlier stage of global invasion. The remaining members of the complex are regionally endemic, varying in their pest status and degree of polyphagy. In addition to patterns of invasion and endemism, our results provide a framework both for identifying members of the complex based on their DNA barcode, and for future species delimiting efforts.

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a global human health problem causing infections in both hospitals and the community. Companion animals, such as cats, dogs, and horses, are also frequently colonized by MRSA and can become infected. We sequenced the genomes of 46 multilocus sequence type (ST) 22 MRSA isolates from cats and dogs in the United Kingdom and compared these to an extensive population framework of human isolates from the same lineage. Phylogenomic analyses showed that all companion animal isolates were interspersed throughout the epidemic MRSA-15 (EMRSA-15) pandemic clade and clustered with human isolates from the United Kingdom, with human isolates basal to those from companion animals, suggesting a human source for isolates infecting companion animals. A number of isolates from the same veterinary hospital clustered together, suggesting that as in human hospitals, EMRSA-15 isolates are readily transmitted in the veterinary hospital setting. Genome-wide association analysis did not identify any host-specific single nucleotide polymorphisms (SNPs) or virulence factors. However, isolates from companion animals were significantly less likely to harbor a plasmid encoding erythromycin resistance. When this plasmid was present in animal-associated isolates, it was more likely to contain mutations mediating resistance to clindamycin. This finding is consistent with the low levels of erythromycin and high levels of clindamycin used in veterinary medicine in the United Kingdom. This study furthers the “one health” view of infectious diseases that the pathogen pool of human and animal populations are intrinsically linked and provides evidence that antibiotic usage in animal medicine is shaping the population of a major human pathogen.IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is major problem in human medicine. Companion animals, such as cats, dogs, and horses, can also become colonized and infected by MRSA. Here, we demonstrate that a shared population of an important and globally disseminated lineage of MRSA can infect both humans and companion animals without undergoing host adaptation. This suggests that companion animals might act as a reservoir for human infections. We also show that the isolates from companion animals have differences in the presence of certain antibiotic resistance genes. This study furthers the “one health” view of infectious diseases by demonstrating that the pool of MRSA isolates in the human and animal populations are shared and highlights how different antibiotic usage patterns between human and veterinary medicine can shape the population of bacterial pathogens.

Intracellular replication within specialized vacuoles and cell-to-cell spread in the tissue are essential for the virulence of Salmonella enterica. By observing infection dynamics at the single-cell level in vivo, we have discovered that the Salmonella pathogenicity island 2 (SPI-2) type 3 secretory system (T3SS) is dispensable for growth to high intracellular densities. This challenges the concept that intracellular replication absolutely requires proteins delivered by SPI-2 T3SS, which has been derived largely by inference from in vitro cell experiments and from unrefined measurement of net growth in mouse organs. Furthermore, we infer from our data that the SPI-2 T3SS mediates exit from infected cells, with consequent formation of new infection foci resulting in bacterial spread in the tissues. This suggests a new role for SPI-2 in vivo as a mediator of bacterial spread in the body. In addition, we demonstrate that very similar net growth rates of attenuated salmonellae in organs can be derived from very different underlying intracellular growth dynamics.

Although there have been great advances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowledge of its importance to virulence. In this study we have explored the contribution of the bacterial cytoskeleton to the ability of Salmonella to express and assemble virulence factors and cause disease. The bacterial actin-like protein MreB polymerises into helical filaments and interacts with other cytoskeletal elements including MreC to control cell-shape. As mreB appears to be an essential gene, we have constructed a viable ΔmreC depletion mutant in Salmonella. Using a broad range of independent biochemical, fluorescence and phenotypic screens we provide evidence that the Salmonella pathogenicity island-1 type three secretion system (SPI1-T3SS) and flagella systems are down-regulated in the absence of MreC. In contrast the SPI-2 T3SS appears to remain functional. The phenotypes have been further validated using a chemical genetic approach to disrupt the functionality of MreB. Although the fitness of ΔmreC is reduced in vivo, we observed that this defect does not completely abrogate the ability of Salmonella to cause disease systemically. By forcing on expression of flagella and SPI-1 T3SS in trans with the master regulators FlhDC and HilA, it is clear that the cytoskeleton is dispensable for the assembly of these structures but essential for their expression. As two-component systems are involved in sensing and adapting to environmental and cell surface signals, we have constructed and screened a panel of such mutants and identified the sensor kinase RcsC as a key phenotypic regulator in ΔmreC. Further genetic analysis revealed the importance of the Rcs two-component system in modulating the expression of these virulence factors. Collectively, these results suggest that expression of virulence genes might be directly coordinated with cytoskeletal integrity, and this regulation is mediated by the two-component system sensor kinase RcsC.

Transplantation of disaggregated myoblasts from normal donor to the muscles of a diseased host, or reimplantation of genetically modified host myoblasts, has been suggested as a possible route to therapy for inherited myopathies such as Duchenne muscular dystrophy, or to supply missing proteins that are required systemically in diseases such as hemophilia. With two exceptions, studies of myoblast transfer in the mouse have involved transplantation of donor myoblasts isolated from adult or neonatal skeletal muscle satellite cells. In this study we present evidence that thymic myoid cells are capable of participating in the regeneration of postnatal skeletal muscle, resulting in the expression of donor-derived proteins such as dystrophin and retrovirally encoded proteins such as β-galactosidase within host muscles. This leads us to conclude that thymic myoid cells may provide an alternative to myoblasts derived from skeletal muscle as a source of myogenic cells for myoblast transfer.