Unique functional diversity during early Cenozoic mammal radiation of North America.

Mammals influence nearly all aspects of energy flow and habitat structure in modern terrestrial ecosystems. However, anthropogenic effects have probably altered mammalian community structure, raising the question of how past perturbations have done so. We used functional diversity (FD) to describe how the structure of North American mammal palaeocommunities changed over the past 66 Ma, an interval spanning the radiation following the K/Pg and several subsequent environmental disruptions including the Palaeocene-Eocene Thermal Maximum (PETM), the expansion of grassland, and the onset of Pleistocene glaciation. For 264 fossil communities, we examined three aspects of ecological function: functional evenness, functional richness and functional divergence. We found that shifts in FD were associated with major ecological and environmental transitions. All three measures of FD increased immediately following the extinction of the non-avian dinosaurs, suggesting that high degrees of ecological disturbance can lead to synchronous responses both locally and continentally. Otherwise, the components of FD were decoupled and responded differently to environmental changes over the last ~56 Myr.

Human disturbance increases spatiotemporal associations among mountain forest terrestrial mammal species.

Spatial and temporal associations between sympatric species underpin biotic interactions, structure ecological assemblages, and sustain ecosystem functioning and stability. However, the resilience of interspecific spatiotemporal associations to human activity remains poorly understood, particularly in mountain forests where anthropogenic impacts are often pervasive. Here, we applied context-dependent Joint Species Distribution Models to a systematic camera-trap survey dataset from a global biodiversity hotspot in eastern Himalayas to understand how prominent human activities in mountain forests influence species associations within terrestrial mammal communities. We obtained 10,388 independent detections of 17 focal species (12 carnivores and five ungulates) from 322 stations over 43,163 camera days of effort. We identified a higher incidence of positive associations in habitats with higher levels of human modification (87%) and human presence (83%) compared to those located in habitats with lower human modification (64%) and human presence (65%) levels. We also detected a significant reduction of pairwise encounter time at increasing levels of human disturbance, corresponding to more frequent encounters between pairs of species. Our findings indicate that human activities can push mammals together into more frequent encounters and associations, which likely influences the coexistence and persistence of wildlife, with potential far-ranging ecological consequences.

Where Do Core Thalamocortical Axons Terminate in Mammalian Neocortex When There Is No Cytoarchitecturally Distinct Layer 4?

Although the mammalian cerebral cortex is most often described as a hexalaminar structure, there are cortical areas (primary motor cortex) and species (elephants, cetaceans, and hippopotami), where a cytoarchitecturally indistinct, or absent, layer 4 is noted. Thalamocortical projections from the core, or first order, thalamic system terminate primarily in layers 4/inner 3. We explored the termination sites of core thalamocortical projections in cortical areas and in species where there is no cytoarchitecturally distinct layer 4 using the immunolocalization of vesicular glutamate transporter 2, a known marker of core thalamocortical axon terminals, in 31 mammal species spanning the eutherian radiation. Several variations from the canonical cortical column outline of layer 4 and core thalamocortical inputs were noted. In shrews/microchiropterans, layer 4 was present, but many core thalamocortical projections terminated in layer 1 in addition to layers 4 and inner 3. In primate primary visual cortex, the sublaminated layer 4 was associated with a specialized core thalamocortical projection pattern. In primate primary motor cortex, no cytoarchitecturally distinct layer 4 was evident and the core thalamocortical projections terminated throughout layer 3. In the African elephant, cetaceans, and river hippopotamus, no cytoarchitecturally distinct layer 4 was observed and core thalamocortical projections terminated primarily in inner layer 3 and less densely in outer layer 3. These findings are contextualized in terms of cortical processing, perception, and the evolutionary trajectory leading to an indistinct or absent cortical layer 4.

Andrea L. Graham.

Interview with Andrea Graham, who studies the ecological and evolutionary causes of immunological heterogeneity in mammals at Princeton University.

Predictability of ecological and evolutionary dynamics in a changing world.

Ecological and evolutionary predictions are being increasingly employed to inform decision-makers confronted with intensifying pressures on biodiversity. For these efforts to effectively guide conservation actions, knowing the limit of predictability is pivotal. In this study, we provide realistic expectations for the enterprise of predicting changes in ecological and evolutionary observations through time. We begin with an intuitive explanation of predictability (the extent to which predictions are possible) employing an easy-to-use metric, predictive power PP(t). To illustrate the challenge of forecasting, we then show that among insects, birds, fishes and mammals, (i) 50% of the populations are predictable at most 1 year in advance and (ii) the median 1-year-ahead predictive power corresponds to a prediction R 2 of only 20%. Predictability is not an immutable property of ecological systems. For example, different harvesting strategies can impact the predictability of exploited populations to varying degrees. Moreover, incorporating explanatory variables, accounting for time trends and considering multivariate time series can enhance predictability. To effectively address the challenge of biodiversity loss, researchers and practitioners must be aware of the information within the available data that can be used for prediction and explore efficient ways to leverage this knowledge for environmental stewardship.

Origins of mammalian vertebral function revealed through digital bending experiments.

Unravelling the functional steps that underlie major transitions in the fossil record is a significant challenge for biologists owing to the difficulties of interpreting functional capabilities of extinct organisms. New computational modelling approaches provide exciting avenues for testing function in the fossil record. Here, we conduct digital bending experiments to reconstruct vertebral function in non-mammalian synapsids, the extinct forerunners of mammals, to provide insights into the functional underpinnings of the synapsid-mammal transition. We estimate range of motion and stiffness of intervertebral joints in eight non-mammalian synapsid species alongside a comparative sample of extant tetrapods, including salamanders, reptiles and mammals. We show that several key aspects of mammalian vertebral function evolved outside crown Mammalia. Compared to early diverging non-mammalian synapsids, cynodonts stabilized the posterior trunk against lateroflexion, while evolving axial rotation in the anterior trunk. This was later accompanied by posterior sagittal bending in crown mammals, and perhaps even therians specifically. Our data also support the prior hypothesis that functional diversification of the mammalian trunk occurred via co-option of existing morphological regions in response to changing selective demands. Thus, multiple functional and evolutionary steps underlie the origin of remarkable complexity in the mammalian backbone.

Convergent evolution toward a slow pace of life predisposes insular endotherms to anthropogenic extinctions.

Island vertebrates have evolved a number of morphological, physiological, and life history characteristics that set them apart from their mainland relatives. However, to date, the evolution of metabolism and its impact on the vulnerability to extinction of insular vertebrates remains poorly understood. This study used metabolic data from 2813 species of tetrapod vertebrates, including 695 ectothermic and 2118 endothermic species, to reveal that island mammals and birds evolved convergent metabolic strategies toward a slow pace of life. Insularity was associated with shifts toward slower metabolic rates and greater generation lengths in endotherms, while insularity just drove the evolution of longer generation lengths in ectotherms. Notably, a slow pace of life has exacerbated the extinction of insular endemic species in the face of anthropogenic threats. These findings have important implications for understanding physiological adaptations associated with the island syndrome and formulating conservation strategies across taxonomic groups with different metabolic modes.

Absence of Leishmania spp. DNA in road-killed wild mammals in Southern Brazil.

Leishmaniasis are neglected diseases transmitted by vectors that affect domestic and wild animals, including humans. Due to its incidence and lethality, this zoonosis is a worrying public health problem, making it essential to identify all links in the transmission chain. Infection of wild mammals by Leishmania spp. remains poorly understood, especially in southern Brazil. Therefore, the objective was to research, using the PCR technique, the presence of Leishmania spp. DNA in road-killed wild mammals in Southern Brazil. Carcasses of 96 animals were collected from highways in the Pelotas microregion, Rio Grande do Sul, southern Brazil and subjected to necropsies. Tissue fragments (spleen, skin, liver, kidney, heart, lung, lymph nodes, bone marrow and blood) were collected and genomic DNA was extracted. PCR protocols targeting the ITS1, kDNA and 18S genes were tested. We found no evidence of Leishmania spp. circulation in the studied population. However, epidemiological studies like this one are of great relevance, as they allow monitoring of the occurrence of pathogens and help identify possible risk areas. As these animals act as epidemiological markers for the presence of the microorganism, studies must be carried out continuously to understand whether there are sources of infection in the region.

Hyperbolic discounting underpins response curves of mammalian avoidance behaviour.

As humans clear natural habitat, they are brought into increased conflict with wild animals. Some conflict is direct (e.g. elevated exposure of people to predators), some indirect (e.g. abandoning suitable habitat because of human activity). The magnitude of avoidance is expected to track frequency of human activity, but the type of response is an open question. We postulated that animals do not respond passively to increased disturbance nor does response follow a power law; instead, their ability to estimate magnitude leads to 'discounting' behaviour, as in classic time-to-reward economic models in which individuals discount larger value (or risk) in more distant time. We used a 10-year camera dataset from southern California to characterize response curves of seven mammal species. Bayesian regressions of two non-discounting models (exponential and inverse polynomial) and two discounting models (hyperbolic and harmonic) revealed that the latter better fit response curves. The Arps equation, from petroleum extraction modelling, was used to estimate a discount exponent, a taxon-specific 'sensitivity' to humans, yielding a general model across species. Although discounting can mean mammal activity recovers rapidly after disturbance, increased recreational pressure on reserves limits recovery potential, highlighting a need to strike a balance between animal conservation and human use.

Tetrapod sperm length evolution in relation to body mass is shaped by multiple trade-offs.

Sperm length is highly variable across species and many questions about its variation remain open. Although variation in body mass may affect sperm length evolution through its influence on multiple factors, the extent to which sperm length variation is linked to body mass remains elusive. Here, we use the Pareto multi-task evolution framework to investigate the relationship between sperm length and body mass across tetrapods. We find that tetrapods occupy a triangular Pareto front, indicating that trade-offs shape the evolution of sperm length in relation to body mass. By exploring the factors predicted to influence sperm length evolution, we find that sperm length evolution is mainly driven by sperm competition and clutch size, rather than by genome size. Moreover, the triangular Pareto front is maintained within endotherms, internal fertilizers, mammals and birds, suggesting similar evolutionary trade-offs within tetrapods. Finally, we demonstrate that the Pareto front is robust to phylogenetic dependencies and finite sampling bias. Our findings provide insights into the evolutionary mechanisms driving interspecific sperm length variation and highlight the importance of considering multiple trade-offs in optimizing reproductive traits.

The mechanism of mammalian proton-coupled peptide transporters.

Proton-coupled oligopeptide transporters (POTs) are of great pharmaceutical interest owing to their promiscuous substrate binding site that has been linked to improved oral bioavailability of several classes of drugs. Members of the POT family are conserved across all phylogenetic kingdoms and function by coupling peptide uptake to the proton electrochemical gradient. Cryo-EM structures and alphafold models have recently provided new insights into different conformational states of two mammalian POTs, SLC15A1, and SLC15A2. Nevertheless, these studies leave open important questions regarding the mechanism of proton and substrate coupling, while simultaneously providing a unique opportunity to investigate these processes using molecular dynamics (MD) simulations. Here, we employ extensive unbiased and enhanced-sampling MD to map out the full SLC15A2 conformational cycle and its thermodynamic driving forces. By computing conformational free energy landscapes in different protonation states and in the absence or presence of peptide substrate, we identify a likely sequence of intermediate protonation steps that drive inward-directed alternating access. These simulations identify key differences in the extracellular gate between mammalian and bacterial POTs, which we validate experimentally in cell-based transport assays. Our results from constant-PH MD and absolute binding free energy (ABFE) calculations also establish a mechanistic link between proton binding and peptide recognition, revealing key details underpining secondary active transport in POTs. This study provides a vital step forward in understanding proton-coupled peptide and drug transport in mammals and pave the way to integrate knowledge of solute carrier structural biology with enhanced drug design to target tissue and organ bioavailability.

The cells in our body are sealed by a surrounding membrane that allows them to control which molecules can enter or leave. Desired molecules are often imported via transport proteins that require a source of energy. One way that transporter proteins achieve this is by simultaneously moving positively charged particles called protons across the membrane. Proteins called POTs (short for proton-coupled oligopeptide transporters) use this mechanism to import small peptides and drugsin to the cells of the kidney and small intestine. Sitting in the centre of these transporters is a pocket that binds to the imported peptide which has a gate on either side: an outer gate that opens towards the outside of the cell, and an inner gate that opens towards the cell's interior. The movement of protons from the outer to the inner gate is thought to shift the shape of the transporter from an outwards to an inwards-facing state. However, the molecular details of this energetic coupling are not well understood. To explore this, Lichtinger et al. used computer simulations to pinpoint where protons bind on POTs to trigger the gates to open. The simulations proposed that two sites together make up the outward-facing gate, which opens upon proton binding. Lichtinger et al. then validated these sites experimentally in cultured human cells that produce mutant POTs. After the desired peptide/drug has attached to the binding pocket, the protons then move to two more sites further down the transporter. This triggers the inner gate to open, which ultimately allows the small molecule to move into the cell. These findings represent a significant step towards understanding how POTs transport their cargo. Since POTs can transport a range of drugs from the digestive tract into the body, these results could help researchers design molecules that are better absorbed. This could lead to more orally available medications, making it easier for patients to adhere to their treatment regimen.

Monitoring of Organochlorine Pesticides (OCP) in Hair Samples of Wild Herbivorous Mammals Living in Remote and Protected Areas of the Far East and Siberia of Russia.

Monitoring wildlife exposure to biological hazards is a critical component of the wildlife risk assessment. In this study 38 hair samples were collected from 8 different species from ten districts of Russian Far East and Siberia and analysed for the presence of organochlorine pesticides (OCP). 50% of the samples were contaminated with - p, p'-DDT, α-HCH and DDD. DDT was the main contaminant found in 13 sample at concentrations range of 14.3 to 369.5 pg/mg hair, mean 91.9 ± 89.7 pg/mg. α-HCH was detected in three samples with the concentrations range 29.9-180.2 pg/mg. The p, p'-DDD was found only in one hair sample of Siberian roe deer from Altai region at 52.6 pg/mg. The exposure level is depended on animals habitat location. The most contaminated region is Terney district which is in the proximity to the borders with China and North Korea where OCP are still in use.

The reverse TRBV30 gene of mammals: a defect or superiority in evolution?

At the 3' end of the C2 gene in the mammalian TRB locus, a distinct reverse TRBV30 gene (named TRBV31 in mice) has been conserved throughout evolution. In the fully annotated TRB locus of 14 mammals (including six orders), we observed noteworthy variations in the localization and quality of the reverse V30 genes and Recombination Signal Sequences (RSSs) in the gene trees of 13 mammals. Conversely, the forward V29 genes and RSSs were generally consistent with the species tree of their corresponding species. This finding suggested that the evolution of the reverse V30 gene was not synchronous and likely played a crucial role in regulating adaptive immune responses. To further investigate this possibility, we utilized single-cell TCR sequencing (scTCR-seq) and high-throughput sequencing (HTS) to analyze TCRß CDR3 repertoires from both central and peripheral tissues of Primates (Homo sapiens and Macaca mulatta), Rodentia (Mus musculus: BALB/c, C57BL/6, and Kunming mice), Artiodactyla (Bos taurus and Bubalus bubalis), and Chiroptera (Rhinolophus affinis and Hipposideros armige). Our investigation revealed several novel observations: (1) The reverse V30 gene exhibits classical rearrangement patterns adhering to the '12/23 rule' and the 'D-J rearrangement preceding the V-(D-J) rearrangement'. This results in the formation of rearranged V30-D2J2, V30-D1J1, and V30-D1J2. However, we also identified 'special rearrangement patterns' wherein V30-D rearrangement preceding D-J rearrangement, giving rise to rearranged V30-D2-J1 and forward Vx-D2-J. (2) Compared to the 'deletional rearrangement' (looping out) of forward V1-V29 genes, the reverse V30 gene exhibits preferential utilization with 'inversional rearrangement'. This may be attributed to the shorter distance between the V30 gene and D gene and the 'inversional rearrangement' modes. In summary, in the mammalian TRB locus, the reverse V30 gene has been uniquely preserved throughout evolution and preferentially utilized in V(D)J recombination, potentially serving a significant role in adaptive immunity. These results will pave the way for novel and specialized research into the mechanisms, efficiency, and function of V(D)J recombination in mammals.

Green spaces contribute to structural resilience of the gut microbiota in urban mammals.

The gut microbiome of wild animals is subject to various environmental influences, including those associated with human-induced alterations to the environment. We investigated how the gut microbiota of a synurbic rodent species, the striped field mouse (Apodemus agrarius), change in cities of varying sizes, seeking the urban microbiota signature for this species. Fecal samples for analysis were collected from animals living in non-urbanized areas and green spaces of different-sized cities (Poland). Metagenomic 16S rRNA gene sequencing and further bioinformatics analyses were conducted. Significant differences in the composition of gut microbiomes among the studied populations were found. However, the observed changes were dependent on local habitat conditions, without strong evidence of a correlation with the size of the urbanized area. The results suggest that ecological detachment from a more natural, non-urban environment does not automatically lead to the development of an "urban microbiome" model in the studied rodent. The exposure to the natural environment in green spaces may serve as a catalyst for microbiome transformations, providing a previously underestimated contribution to the maintenance of native gut microbial communities in urban mammals.

Spatially explicit predictions of food web structure from regional-level data.

Knowledge about how ecological networks vary across global scales is currently limited given the complexity of acquiring repeated spatial data for species interactions. Yet, recent developments in metawebs highlight efficient ways to first document possible interactions within regional species pools. Downscaling metawebs towards local network predictions is a promising approach to using the current data to investigate the variation of networks across space. However, issues remain in how to represent the spatial variability and uncertainty of species interactions, especially for large-scale food webs. Here, we present a probabilistic framework to downscale a metaweb based on the Canadian mammal metaweb and species occurrences from global databases. We investigated how our approach can be used to represent the variability of networks and communities between ecoregions in Canada. Species richness and interactions followed a similar latitudinal gradient across ecoregions but simultaneously identified contrasting diversity hotspots. Network motifs revealed additional areas of variation in network structure compared with species richness and number of links. Our method offers the potential to bring global predictions down to a more actionable local scale, and increases the diversity of ecological networks that can be projected in space. This article is part of the theme issue 'Connected interactions: enriching food web research by spatial and social interactions'.

Characterization of antimicrobial resistance profiles in Escherichia coli isolated from captive mammals in Ecuador.

BACKGROUND: This study focuses on the AMR profiles in E. coli isolated from captive mammals at EcoZoo San Martín, Baños de Agua Santa, Ecuador, highlighting the role of wildlife as reservoirs of resistant bacteria. AIMS: The aim of this research is to investigate the antimicrobial resistance profiles of E. coli strains isolated from various species of captive mammals, emphasizing the potential zoonotic risks and the necessity for integrated AMR management strategies. MATERIALS & METHODS: A total of 189 fecal samples were collected from 70 mammals across 27 species. These samples were screened for E. coli, resulting in 90 identified strains. The resistance profiles of these strains to 16 antibiotics, including 10 ß-lactams and 6 non-ß-lactams, were determined using the disk diffusion method. Additionally, the presence of Extended-Spectrum Beta-Lactamase (ESBL) genes and other resistance genes was analyzed using PCR. RESULTS: Significant resistance was observed, with 52.22% of isolates resistant to ampicillin, 42.22% to ceftriaxone and cefuroxime, and 27.78% identified as ESBL-producing E. coli. Multiresistance (resistance to more than three antibiotic groups) was found in 35.56% of isolates. Carnivorous and omnivorous animals, particularly those with prior antibiotic treatments, were more likely to harbor resistant strains. DISCUSSION: These findings underscore the role of captive mammals as indicators of environmental AMR. The high prevalence of resistant E. coli in these animals suggests that zoos could be significant reservoirs for the spread of antibiotic-resistant bacteria. The results align with other studies showing that diet and antibiotic treatment history influence resistance profiles. CONCLUSION: The study highlights the need for an integrated approach involving veterinary care, habitat management, and public awareness to prevent captive wildlife from becoming reservoirs of antibiotic-resistant bacteria. Improved waste management practices and responsible antibiotic use are crucial to mitigate the risks of AMR in zoo environments and reduce zoonotic threats.

Mammal responses to human recreation depend on landscape context.

Rapid growth in outdoor recreation may have important and varied effects on terrestrial mammal communities. Few studies have investigated factors influencing variation in observed responses of multiple mammal species to recreation. We used data from 155 camera traps, in western Alberta (Canada), and a hierarchical Bayesian community modelling framework to document 15 mammal species responses to recreation, test for differential responses between predators and prey, and evaluate the influence of local context. Factors characterizing context were trail designation (i.e., use by motorized vs non-motorized), management type, forest cover, landscape disturbance, and season. We used three measures to characterize variation in recreation pressure: distance to trail, trail density, and an index of recreation intensity derived from the platform Strava. We found limited evidence for strong or consistent effects of recreation on mammal space use. However, mammal space use was better explained by an interaction between recreation and the influencing factors than by either on their own. The strongest interaction was between trail density and management type; mammals were more likely to avoid sites near a higher density of trails in areas with more restrictive management. We found that responses to recreation varied with the trail designation, although there were not clear or consistent differences between responses to trails designated for motorized vs. non-motorized use. Overall, we found that responses were species- and context-dependent. Limiting the density of trails may be important for reducing negative impacts to mammals within conservation areas. We show that using multiple measures of recreation yields more insight into the varied effects of human disturbances on wildlife. We recommend investigating how different characteristics of recreation (noise, speed, and visibility) influence animal behaviors. Multispecies monitoring and modelling across multiple landscapes that vary in recreation pressure can lead to an adaptive management approach to ensuring outdoor recreation coexistence with wildlife.

Mechanisms of DNA Damage Response in Mammalian Oocytes.

DNA damage poses a significant challenge to all eukaryotic cells, leading to mutagenesis, genome instability and senescence. In somatic cells, the failure to repair damaged DNA can lead to cancer development, whereas, in oocytes, it can lead to ovarian dysfunction and infertility. The response of the cell to DNA damage entails a series of sequential and orchestrated events including sensing the DNA damage, activating DNA damage checkpoint, chromatin-related conformational changes, activating the DNA damage repair machinery and/or initiating the apoptotic cascade. This chapter focuses on how somatic cells and mammalian oocytes respond to DNA damage. Specifically, we will discuss how and why fully grown mammalian oocytes differ drastically from somatic cells and growing oocytes in their response to DNA damage.

Genome-Wide Profiling of Cis-regulatory Elements in Mammalian Skin.

The modulation of cis-regulatory elements (e.g., enhancers and promoters) is a major mechanism by which gene expression can be controlled in a temporal and spatially restricted manner. However, methods for both identifying these elements and inferring their activity are limited and often require a substantial investment of time, money, and resources. Here, using mammalian skin as a model, we demonstrate a streamlined protocol by which these hurdles can be overcome using a novel chromatin profiling technique (CUT&RUN) to map histone modifications genome-wide. This protocol can be used to map the location and activity of putative cis-regulatory elements, providing mechanistic insight into how differential gene expression is controlled in mammalian tissues.

Development of functional spermatozoa in mammalian spermiogenesis.

Infertility is a global health problem affecting one in six couples, with 50% of cases attributed to male infertility. Spermatozoa are male gametes, specialized cells that can be divided into two parts: the head and the flagellum. The head contains a vesicle called the acrosome that undergoes exocytosis and the flagellum is a motility apparatus that propels the spermatozoa forward and can be divided into two components, axonemes and accessory structures. For spermatozoa to fertilize oocytes, the acrosome and flagellum must be formed correctly. In this Review, we describe comprehensively how functional spermatozoa develop in mammals during spermiogenesis, including the formation of acrosomes, axonemes and accessory structures by focusing on analyses of mouse models.