Homodimeric Granzyme A Opsonizes Mycobacterium tuberculosis and Inhibits Its Intracellular Growth in Human Monocytes via Toll-Like Receptor 4 and CD14.

Mycobacterium tuberculosis (Mtb)-specific γ9δ2 T cells secrete granzyme A (GzmA) protective against intracellular Mtb growth. However, GzmA-enzymatic activity is unnecessary for pathogen inhibition, and the mechanisms of GzmA-mediated protection remain unknown. We show that GzmA homodimerization is essential for opsonization of mycobacteria, altered uptake into human monocytes, and subsequent pathogen clearance within the phagolysosome. Although monomeric and homodimeric GzmA bind mycobacteria, only homodimers also bind cluster of differentiation 14 (CD14) and Toll-like receptor 4 (TLR4). Without access to surface-expressed CD14 and TLR4, GzmA fails to inhibit intracellular Mtb. Upregulation of Rab11FIP1 was associated with inhibitory activity. Furthermore, GzmA colocalized with and was regulated by protein disulfide isomerase AI (PDIA1), which cleaves GzmA homodimers into monomers and prevents Mtb inhibitory activity. These studies identify a previously unrecognized role for homodimeric GzmA structure in opsonization, phagocytosis, and elimination of Mtb in human monocytes, and they highlight PDIA1 as a potential host-directed therapy for prevention and treatment of tuberculosis, a major human disease.

Hypoconulid loss in cercopithecins: Functional and developmental considerations.

Cercopithecins differ from papionins in lacking a M3 hypoconulid. Although this loss may be related to dietary differences, the functional and developmental ramifications of hypoconulid loss are currently unclear. The following makes use of dental topographic analysis to quantify shape variation in a sample of cercopithecin M3s, as well as in a sample of Macaca, which has a hypoconulid. To help understand the consequences of hypoconulid loss, Macaca M3s were virtually cropped to remove the hypoconulid and were also subjected to dental topographic analysis. The patterning cascade model and the inhibitory cascade model attempt to explain variation in cusp pattern and molar proportions, respectively. These models have both previously been used to explain patterns of variation in cercopithecines, but have not been examined in the context of hypoconulid loss. For example, previous work suggests that earlier developing cusps impact the development of later developing cusps (i.e., the hypoconulid) and that cercopithecines do not conform to the predictions of the inhibitory cascade model in that the size of the molars is not linear moving distally. Results of the current study suggest that the loss of the hypoconulid is associated with a reduction in dental topography among cercopithecins, which is potentially related to diet, although the connection to diet is not necessarily clear. Results also suggest that the loss of the hypoconulid can be explained by the patterning cascade model, and that hypoconulid loss explains the apparent lack of support for the inhibitory cascade model among cercopithecines. These findings highlight the importance of a holistic approach to studying variation in molar proportions and developmental models.

Mammalian molar complexity follows simple, predictable patterns.

Identifying developmental explanations for the evolution of complex structures like mammalian molars is fundamental to studying phenotypic variation. Previous study showed that a "morphogenetic gradient" of molar proportions was explained by a balance between inhibiting/activating activity from earlier developing molars, termed the inhibitory cascade model (ICM). Although this model provides an explanation for variation in molar proportions, what remains poorly understood is if molar shape, or specifically complexity (i.e., the number of cusps, crests), can be explained by the same developmental model. Here, we show that molar complexity conforms to the ICM, following a linear, morphogenetic gradient along the molar row. Moreover, differing levels of inhibiting/activating activity produce contrasting patterns of molar complexity depending on diet. This study corroborates a model for the evolution of molar complexity that is developmentally simple, where only small-scale developmental changes need to occur to produce change across the entire molar row, with this process being mediated by an animal's ecology. The ICM therefore provides a developmental framework for explaining variation in molar complexity and a means for testing developmental hypotheses in the broader context of mammalian evolution.

Metal Halide Superionic Conductors for All-Solid-State Batteries.

ConspectusRechargeable all-solid-state Li batteries (ASSLBs) are considered to be the next generation of electrochemical energy storage systems. The development of solid-state electrolytes (SSEs), which are key materials for ASSLBs, is therefore one of the most important subjects in modern energy storage chemistry. Various types of electrolytes such as polymer-, oxide-, and sulfide-based SSEs have been developed to date and the discovery of new superionic conductors is still ongoing. Metal-halide SSEs (Li-M-X, where M is a metal element and X is a halogen) are emerging as new candidates with a number of attractive properties and advantages such as wide electrochemical stability windows (0.36-6.71 V vs Li/Li+) and better chemical stability toward cathode materials compared to other SSEs. Furthermore, some of the metal-halide SSEs (such as the Li3InCl6 developed by our group) can be directly synthesized at large scales in a water solvent, removing the need for special apparatus or handling in an inert atmosphere. Based on the recent advances, herein we focus on the topic of metal-halide SSEs, aiming to provide a guidance toward further development of novel halide SSEs and push them forward to meet the multiple requirements of energy storage devices.In this Account, we describe our recent progress in developing metal halide SSEs and focus on some newly reported findings based on state-of-the-art publications on this topic. A discussion on the structure of metal-halide SSEs will be first explored. Subsequently, we will illustrate the effective approaches to enhance the ionic conductivities of metal halide SSEs including the effect of anion sublattice framework, the regulation of site occupation and disorder, and defect engineering. Specifically, we demonstrated that proper structural framework, balanced Li+/vacancy concentration, and reduced blocking effect can promote fast Li+ migration for metal halide SSEs. Moreover, humidity stability and degradation chemistry of metal halide SSEs have been summarized for the first time. Some examples of the application of metal halide SSEs with stability toward humidity have been demonstrated. Direct synthesis of halide SSEs on cathode materials by the water-mediated route has been used to eliminate the interfacial challenges of ASSLBs and has been shown to act as an interfacial modifier for high-performance all-solid-state Li-O2 batteries. Taken together, this Account on metal halide SSEs will provide an insightful perspective over the recent development and future research directions that can lead to advanced electrolytes.

A transient reduction in circulating corticosterone reduces object neophobia in male house sparrows.

Aversive reactions to novelty (or "neophobia") have been described in a wide variety of different animal species and can affect an individual's ability to exploit new resources and avoid potential dangers. However, despite its ecological importance, the proximate causes of neophobia are poorly understood. In this study, we tested the role of glucocorticoid hormones in neophobia in wild-caught house sparrows (Passer domesticus, n = 11 males) by giving an injection of the drug mitotane that reduced endogenous corticosterone for several days or a vehicle control, and then examined the latency to feed when the food dish was presented with or without a novel object in, on, or near the dish. Each sparrow was exposed to multiple novel object and control trials and received both vehicle control and mitotane treatments, with a week between treatments to allow the drug to wash out. As found previously, all novel objects significantly increased sparrows' latency to feed compared to no object present. Reducing corticosterone using mitotane significantly reduced the latency to feed in the presence of novel objects. In control trials without objects, mitotane had no significant effects on feeding time. Although we have shown that corticosterone affects neophobia, further studies using specific receptor agonists and antagonists will help clarify the neurobiological mechanisms involved and determine whether baseline or stress-induced corticosterone is driving this effect. These results suggest that increased glucocorticoids (e.g., due to human-induced stressors) could increase neophobia, affecting the ability of individuals to exploit novel resources, and, ultimately, to persist in human-altered environments.

Unveiling the Nature of Pt Single-Atom Catalyst during Electrocatalytic Hydrogen Evolution and Oxygen Reduction Reactions.

Single-atom catalysts (SACs) have attracted significant attention due to their superior catalytic activity and selectivity. However, the nature of active sites of SACs under realistic reaction conditions is ambiguous. In this work, high loading Pt single atoms on graphitic carbon nitride (g-C3 N4 )-derived N-doped carbon nanosheets (Pt1 /NCNS) is achieved through atomic layer deposition. Operando X-ray absorption spectroscopy (XAS) is performed on Pt single atoms and nanoparticles (NPs) in both the hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR). The operando results indicate that the total unoccupied density of states of Pt 5d orbitals of Pt1 atoms is higher than that of Pt NPs under HER condition, and that a stable Pt oxide is formed during ORR on Pt1 /NCNS, which may suppress the adsorption and activation of O2 . This work unveils the nature of Pt single atoms under realistic HER and ORR conditions, providing a deeper understanding for designing advanced SACs.

Cladogenesis and replacement in the fossil record of Microsyopidae (?Primates) from the southern Bighorn Basin, Wyoming.

The early Eocene of the southern Bighorn Basin, Wyoming, is notable for its nearly continuous record of mammalian fossils. Microsyopinae (?Primates) is one of several lineages that shows evidence of evolutionary change associated with an interval referred to as Biohorizon A. Arctodontomys wilsoni is replaced by a larger species, Arctodontomys nuptus, during the biohorizon interval in what is likely an immigration/emigration or immigration/local extinction event. The latter is then superseded by Microsyops angustidens after the end of the Biohorizon A interval. Although this pattern has been understood for some time, denser sampling has led to the identification of a specimen intermediate in morphology between A. nuptus and M. angustidens, located stratigraphically as the latter is appearing. Because specimens of A. nuptus have been recovered approximately 60 m above the appearance of M. angustidens, it is clear that A. nuptus did not suffer pseudoextinction. Instead, evidence suggests that M. angustidens branched off from a population of A. nuptus, but the latter species persisted. This represents possible evidence of cladogenesis, which has rarely been directly documented in the fossil record. The improved understanding of both evolutionary transitions with better sampling highlights the problem of interpreting gaps in the fossil record as punctuations.

The effect of high wear diets on the relative pulp volume of the lower molars.

OBJECTIVES: One role of dental pulp is in the upkeep and maintenance of dentine. Under wear, odontoblasts in the pulp deposit tertiary dentine to ensure the sensitive internal dental tissues are not exposed and vulnerable to infection. It follows that there may be an adaptive advantage for increasing molar pulp volume in anthropoid primate taxa that are prone to high levels of wear. The relative volume of dental pulp is therefore predicted to covary with dietary abrasiveness (in the sense of including foods that cause high degrees of wear). MATERIALS AND METHODS: We examined relatively unworn lower second molars in pairs of species of extant hominoids, cebids, and pitheciids that vary in the abrasiveness of their diet (n = 36). Using micro-CT scans, we measured the percent of tooth that is pulp (PTP) as the ratio of pulp volume to that of the total volume of the tooth. RESULTS: We found that in each pair of species, the taxa that consume a more abrasive diet had a significantly higher PTP than the closely related taxa that consume a softer diet. CONCLUSIONS: Our results point to an adaptive mechanism in the molars of taxa that consume abrasive diets and are thus subject to higher levels of wear. Our results provide additional understanding of the relationship between dental pulp and diet and may offer insight into the diet of extinct taxa such as Paranthropus boisei or into the adaptive context of the taurodont molars of Neanderthals.

Origin of Superionic Li3Y1-xInxCl6 Halide Solid Electrolytes with High Humidity Tolerance.

The high ionic conductivity, air/humidity tolerance, and related chemistry of Li3MX6 solid-state electrolytes (SSEs, M is a metal element, and X is a halogen) has recently gained significant interest. However, most of the halide SSEs suffer from irreversible chemical degradation when exposed to a humid atmosphere, which originates from hydrolysis. Herein, the function of the M atom in Li3MX6 was clarified by a series of Li3Y1-xInxCl6 (0 ≤ x < 1). When the ratio of In3+ was increased, a gradual structural conversion from the hexagonal-closed-packed (hcp) anion arrangement to cubic-closed-packed (ccp) anion arrangement has been traced. Compared to hcp anion sublattice, the Li3MX6 with ccp anion sublattice reveals faster Li+ migration. The tolerance of Li3Y1-xInxCl6 towards humidity is highly improved when the In3+ content is high enough due to the formation of hydrated intermediates. The correlations among composition, structure, Li+ migration, and humidity stability presented in this work provide insights for designing new halide-based SSEs.

Site-Occupation-Tuned Superionic LixScCl3+xHalide Solid Electrolytes for All-Solid-State Batteries.

The enabling of high energy density of all-solid-state lithium batteries (ASSLBs) requires the development of highly Li+-conductive solid-state electrolytes (SSEs) with good chemical and electrochemical stability. Recently, halide SSEs based on different material design principles have opened new opportunities for ASSLBs. Here, we discovered a series of LixScCl3+x SSEs (x = 2.5, 3, 3.5, and 4) based on the cubic close-packed anion sublattice with room-temperature ionic conductivities up to 3 × 10-3 S cm-1. Owing to the low eutectic temperature between LiCl and ScCl3, LixScCl3+x SSEs can be synthesized by a simple co-melting strategy. Preferred orientation is observed for all the samples. The influence of the value of x in LixScCl3+x on the structure and Li+ diffusivity were systematically explored. With increasing x value, higher Li+, lower vacancy concentration, and less blocking effects from Sc ions are achieved, enabling the ability to tune the Li+ migration. The electrochemical performance shows that Li3ScCl6 possesses a wide electrochemical window of 0.9-4.3 V vs Li+/Li, stable electrochemical plating/stripping of Li for over 2500 h, as well as good compatibility with LiCoO2. LiCoO2/Li3ScCl6/In ASSLB exhibits a reversible capacity of 104.5 mAh g-1 with good cycle life retention for 160 cycles. The observed changes in the ionic conductivity and tuning of the site occupations provide an additional approach toward the design of better SSEs.

A Novel Method for Assessing Enamel Thickness Distribution in the Anterior Dentition as a Signal for Gouging and Other Extractive Foraging Behaviors in Gummivorous Mammals.

Gummivory poses unique challenges to the dentition as gum acquisition may often require that the anterior teeth be adapted to retain a sharp edge and to resist loading because they sometimes must penetrate a highly obdurate substrate during gum extraction by means of gouging or scraping. It has been observed previously that the enamel on the labial surface of the teeth used for extraction is thicker relative to that on the lingual surface in taxa that extract gums, while enamel is more evenly distributed in the anterior teeth of taxa that do not regularly engage in extractive behaviors. This study presents a quantitative methodology for measuring the distribution of labial versus lingual enamel thickness among primate and marsupial taxa in the context of gummivory. Computed microtomography scans of 15 specimens representing 14 taxa were analyzed. Ten measurements were taken at 20% intervals starting from the base of the crown of the extractive tooth to the tip of the cutting edge across the lingual and labial enamel. A method for including worn or broken teeth is also presented. Mann-Whitney U tests, canonical variates analysis, and between-group principal components analysis were used to examine variation in enamel thickness across taxa. Our results suggest that the differential distribution of enamel thickness in the anterior dentition can serve as a signal for gouging behavior; this methodology distinguishes between gougers, scrapers, and nonextractive gummivores. Gouging taxa are characterized by significantly thicker labial enamel relative to the lingual enamel, particularly towards the crown tip. Examination of enamel thickness patterning in these taxa permits a better understanding of the adaptations for the extraction of gums in extant taxa and offers the potential to test hypotheses concerning the dietary adaptations of fossil taxa.

Highly Stable Lithium Metal Anode Interface via Molecular Layer Deposition Zircone Coatings for Long Life Next-Generation Battery Systems.

Herein, molecular layer deposition is used to form a nanoscale "zircone" protective layer on Li metal to achieve stable and long life Li metal anodes. The zircone-coated Li metal shows enhanced air stability, electrochemical performance and high rate capability in symmetrical cell testing. Moreover, as a proof of concept, the protected Li anode is used in a next-generation Li-O2 battery system and is shown to extend the lifetime by over 10-fold compared to the batteries with untreated Li metal. Furthermore, in-situ synchrotron X-ray absorption spectroscopy is used for the first time to study an artificial SEI on Li metal, revealing the electrochemical stability and lithiation of the zircone film. This work exemplifies significant progress towards the development and understanding of MLD thin films for high performance next-generation batteries.

Water-Mediated Synthesis of a Superionic Halide Solid Electrolyte.

To promote the development of solid-state batteries, polymer-, oxide-, and sulfide-based solid-state electrolytes (SSEs) have been extensively investigated. However, the disadvantages of these SSEs, such as high-temperature sintering of oxides, air instability of sulfides, and narrow electrochemical windows of polymers electrolytes, significantly hinder their practical application. Therefore, developing SSEs that have a high ionic conductivity (>10-3  S cm-1 ), good air stability, wide electrochemical window, excellent electrode interface stability, low-cost mass production is required. Herein we report a halide Li+ superionic conductor, Li3 InCl6 , that can be synthesized in water. Most importantly, the as-synthesized Li3 InCl6 shows a high ionic conductivity of 2.04×10-3  S cm-1 at 25 °C. Furthermore, the ionic conductivity can be recovered after dissolution in water. Combined with a LiNi0.8 Co0.1 Mn0.1 O2 cathode, the solid-state Li battery shows good cycling stability.

Structure of the 2,4'-dihydroxyacetophenone dioxygenase from Alcaligenes sp. 4HAP.

The enzyme 2,4'-dihydroxyacetophenone dioxygenase (DAD) catalyses the conversion of 2,4'-dihydroxyacetophenone to 4-hydroxybenzoic acid and formic acid with the incorporation of molecular oxygen. Whilst the vast majority of dioxygenases cleave within the aromatic ring of the substrate, DAD is very unusual in that it is involved in C-C bond cleavage in a substituent of the aromatic ring. There is evidence that the enzyme is a homotetramer of 20.3 kDa subunits, each containing nonhaem iron, and its sequence suggests that it belongs to the cupin family of dioxygenases. In this paper, the first X-ray structure of a DAD enzyme from the Gram-negative bacterium Alcaligenes sp. 4HAP is reported, at a resolution of 2.2 Å. The structure establishes that the enzyme adopts a cupin fold, forming dimers with a pronounced hydrophobic interface between the monomers. The catalytic iron is coordinated by three histidine residues (76, 78 and 114) within a buried active-site cavity. The iron also appears to be tightly coordinated by an additional ligand which was putatively assigned as a carbonate dianion since this fits the electron density optimally, although it might also be the product formate. The modelled carbonate is located in a position which is highly likely to be occupied by the α-hydroxyketone group of the bound substrate during catalysis. Modelling of a substrate molecule in this position indicates that it will interact with many conserved amino acids in the predominantly hydrophobic active-site pocket where it undergoes peroxide radical-mediated heterolysis.

Dental caries in living and extinct strepsirrhines with insights into diet.

Dental caries is one of the most common diseases afflicting modern humans and occurs in both living and extinct non-human primates, as well as other mammalian species. Compared to other primates, less is known about the etiology or frequency of caries among the Strepsirrhini. Given the link between caries and diet, caries frequency may be informative about the dietary ecology of a given animal. Understanding rates of caries in wild populations is also critical to assessing dental health in captive populations. Here, we examine caries frequency in a sample of 36 extant strepsirrhine species (n = 316 individuals) using odontological collections of wild-, non-captive animals housed at the American Museum of Natural History by counting the number of specimens characterized by the disease. Additionally, in the context of studying caries lesions in strepsirrhines, case studies were also conducted to test if similar lesions were found in their fossil relatives. In particular, two fossil strepsirrhine species were analyzed: the earliest Late Eocene Karanisia clarki, and the subfossil lemur Megaladapis madagascariensis. Our results suggest that caries affects 13.92% of the extant individuals we examined. The frugivorous and folivorous taxa were characterized by the highest overall frequency of caries, whereas the insectivores, gummivores, and omnivores had much lower caries frequencies. Our results suggest that caries may be common among wild populations of strepsirrhines, and in fact is more prevalent than in many catarrhines and platyrrhines. These findings have important implications for understanding caries, diet, and health in living and fossil taxa.

Effect of estradiol and predator cues on behavior and brain responses of captive female house sparrows (Passer domesticus).

The presence of predators can cause major changes in animal behavior, but how this interacts with hormonal state and brain activity is poorly understood. We gave female house sparrows (Passer domesticus) in post-molt condition an estradiol (n = 17) or empty implant (n = 16) for 1 week. Four weeks after implant removal, a time when female sparrows show large differences in neuronal activity to conspecific vs. heterospecific song, we exposed birds to either 30 min of conspecific song or predator calls, and video recorded their behavior. Females were then euthanized, and we examined neuronal activity using the expression of the immediate early gene (IEG) ZENK to identify how the acoustic stimuli affected neuronal activation. We predicted that if female sparrows with estradiol implants reduce neuronal activity in response to predator calls as they do to neutral tones and non-predatory heterospecifics, they would show less fear behavior and a decreased ZENK response in brain regions involved in auditory (e.g., caudomedial mesopallium) and threat perception functions (e.g., medial ventral arcopallium) compared to controls. Conversely, we predicted that if females maintain auditory and/or brain sensitivity towards predator calls, then female sparrows exposed to estradiol would not show any differences in ZENK response regardless of playback type. We found that female sparrows were less active during predator playbacks independent of hormone treatment and spent more time feeding during conspecific playback if they had previously been exposed to estradiol. We observed no effect of hormone or sound treatment on ZENK response in any region of interest. Our results suggest that female songbirds maintain vigilance towards predators even when in breeding condition.

Development of ELIP to Assess Physical Literacy for Emerging Adults: A Methodological and Epistemological Challenge.

Purpose: Following increased interest in physical literacy (PL), development of appropriate tools for assessment has become an important next step for its operationalization. To forward the development of such tools, the objective of this study was to build the foundations of the Évaluation de la Littératie Physique (ELIP), designed to help reduce existing tensions in approaches to PL assessment that may be resulting in a low uptake into applied settings. Methods: We followed two steps: (1) the development of the first version of ELIP by deploying a Delphi method (n = 30); and (2) the modification of items through cognitive interviews with emerging adults (n = 32). Results: The expert consensus highlighted four dimensions of PL to be assessed-physical; affective; cognitive; and social-with new perspectives, including a preference for broad motor tests over fitness. Conclusion: Results offer new insights into the assessment of emerging adults' PL, but ELIP still requires further work concerning validity, reliability, and sensitivity.

A qualitative exploration of stakeholder perspectives on a school-based multi-component health promotion nutrition programme.

BACKGROUND: Food for Fitness is an on-going multi-component health promotion programme, delivered in primary and secondary schools by community nutrition assistants. The programme uses nutritional interventions aimed at promoting healthier eating practices for children. This service evaluation investigated the receipt and delivery of the programme, as perceived by local stakeholders who had experienced and administered the service. METHODS: Semi-structured interviews and focus groups were carried out with three key stakeholder groups: health professionals (n = 9), school teachers (n = 10) and senior health officials (n = 3). Qualitative data were transcribed verbatim and received thematic analysis with deductive and inductive processes. RESULTS: Stakeholders reported that the programme contributed to the development of food education and healthy-eating practices of children in the local area. Stakeholders considered that the main concern was the limited capacity and size of the service. They described problems with long-term sustainability in supporting schools with maintaining nutritional interventions, highlighting issues regarding contact, planning and organisation of several interventions. CONCLUSIONS: The findings of the service evaluation inform service management, organisation and ground-level delivery. The use of stakeholder opinion provided contextualised information on the factors that impact on the implementation of the programme. The richness of the qualitative results can guide future planning and provision for similar health promotion nutrition programmes delivered in the school environment.

Novel objects alter immediate early gene expression globally for ZENK and regionally for c-Fos in neophobic and non-neophobic house sparrows.

Neophobia - an animal's reluctance to approach novel objects, try new foods, or explore unfamiliar environments - affects whether animals can adapt to new environments and exploit novel resources. However, despite its importance, the neurobiological mechanisms underlying this personality trait are poorly understood. In this study, we examined regional brain activity using the expression of two immediate early genes (IEGs), ZENK and c-Fos, in response to novel objects or control conditions in captive house sparrows (Passer domesticus, n = 22). When exposed to novel objects, we predicted that we would see differential IEG activity in brain regions involved in regulating stress and emotion (hippocampus, medial ventral arcopallium, lateral septum), reward and learning (striatum), and executive function (NCL) between neophobic and non-neophobic individuals. To classify birds by phenotype, we used behavior trials that tested willingness to approach a food dish in the presence of several different novel objects, habituation to one novel object, and willingness to try several different novel foods. We then exposed birds to a new novel object or a control condition and assessed protein expression of two IEGs in neophobic vs non-neophobic individuals after this final exposure. An analysis of average sparrow feeding times in the presence of novel objects showed a bimodal distribution of neophobia behavior. There was also high repeatability of individual novel object responses, and average responses to all three trial types (novel object, novel food, and habituation to a novel object) were significantly correlated. Although we saw no differences between neophobic and non-neophobic birds in IEG expression in response to novel objects in any of the 6 brain regions examined, there was a significant global decrease in ZENK expression and a significant increase in c-Fos expression in the medial ventral arcopallium and the caudal hippocampus in response to novel objects compared to controls, suggesting that these two regions may be important in novelty detection and threat perception. Additionally, there was no object effect in the rostral hippocampus, which supports the hypothesis that the avian hippocampus may have a rostrocaudal functional gradient similar to the septotemporal gradient in mammals.

The largest and earliest known sample of dental caries in an extinct mammal (Mammalia, Euarchonta, Microsyops latidens) and its ecological implications.

Dental cavities or caries is a common disease among modern humans, affecting almost every adult. Caries frequency has been used to study dietary change in humans over time, based on an inferred tie between the incidence of caries and a carbohydrate-rich diet. However, the disease is not unique to our species. Among non-human primates, there is also variation in caries frequency associated with diet, suggesting that this metric may provide a mechanism for studying diet in broader contexts, and across geological time. To date, very few studies have examined caries among fossil mammals, and none have done so among Eocene mammals. Here, we present our analysis of the largest sample to date of fossil caries in a single extinct mammal species, Microsyops latidens, a stem primate from the early Eocene, which is known from over a thousand specimens from the Southern Bighorn Basin of Wyoming (n = 1030). Our results show that Microsyops latidens is characterized by a high prevalence of dental caries (7.48% of individuals), with notable variation through time, reaching 17.24% of individuals from a particular interval. This interval is also associated with a change in overall dental form, as quantified by dental topographic analysis, which measures functional aspects of the chewing surface of teeth. These observations suggest that this species experienced a shift in their diet to include more fruit or other sugar rich-foods for a short period. Our analysis, therefore, suggests that the diet of M. latidens fluctuated over time, as well as providing a framework for assessing caries in other fossil taxa.