How does evolutionary evaluation illuminate body size among canids?

In this review, we examine mammalian body size as it reflects life history and genomic composition, with a primary focus on canids and the domestication of the gray wolf. The range of variation in body size is greater among Carnivora than any other terrestrial order. In the Canidae, this range is some 2 orders of magnitude. Macroevolutionary patterns (eg, Bergmann's rule and Cope's rule) that have been proposed in the past often fail to comport with modern studies on this aspect of carnivoran evolution. Clades often begin with small to medium size (mesocarnivorans) and diversify mostly in a right-skewed (larger) direction. The observed variation in body size reflects phenotypic plasticity in response to life history. As with many Mammalia, historically high gene flow (hybridization and introgression) among canid lineages has been a crucial source of genomic variation (nuclear and mitochondrial), yielding the potential for high plasticity of phenotypes such as body size. In addition, epigenetic marks connect genetic expression with environmental conditions in the manifested phenotypes. Among Mammalia generally, a larger size is associated with a longer life span, reflecting the foregoing genomic composition and environmental influences over a long geological time. However, the larger modern domestic dog breeds trend toward shorter life spans. The latter appears to reflect genetically mediated phenotypes that emerged secondary to domestication but nonetheless against a background of broadly and deeply conserved developmental and physiological patterns and body plans.

Developmental features of the canid proximocaudal femur.

We continued direct morphological studies of the canid coxofemoral joint, considering early-life spatial relationships around the locus of the proximocaudal joint capsule insertion. Our primary goal was to elucidate the postnatal developmental gross anatomy of the proximocaudal femur, among juveniles across Canidae. From an original database of 267 independent (museum) specimens from 11 canid taxa and 1 hybrid taxon, we identified 29 ancient or modern candidate juvenile specimens (nine taxa and one hybrid taxon). Based on optimal ability to recognize landmarks, the best photographic data were categorized into five groups of four each (n = 20). The data groups approximated early juvenile, early-mid juvenile, mid-juvenile, mid-late juvenile; and young adult stages. In this descriptive photographic essay, we demonstrate the developmental spatial proximity among (a) the dorsal meeting of the respective lateral and medial extensions from the growth centers of the femoral head and greater trochanter; (b) the caudodorsal aspect of the coxofemoral joint capsule attachment; (c) a segment of the proximocaudal femoral shaft physis; and (d) an eventual associated mineralized prominence. The latter occurs frequently but not universally, suggesting natural population variability across taxa. Across taxa and juvenile age categories, the morphology thus supports developmental conservation among ancient and modern Canidae. The biomechanical and biological cause-effect implications are not yet clear. For zoological purposes, we apply the term postdevelopmental mineralized prominence to the residual caudolateral surface feature. We extend the original anatomical work of Morgan in zoological and phylogenic arenas, using direct observation of cleared skeletal specimens.

Morphology-based diagnostics of "protodogs." A commentary to Galeta et al., 2021, Anatomical Record, 304, 42-62, doi: 10.1002/ar.24500.

In a recent article in this journal, Galeta et al., (2020) discussed eight Pleistocene "protodogs" and seven Pleistocene wolves. Those "protodogs" had been diagnosed in earlier publications, based on skull morphology. We re-examined the Galeta et al. paper to offer comments on their observed outcomes, and the conclusion of presumed domestication. Of seven metrics that the authors used, five differed statistically between their two groups. However, from more elaborate studies, some of those same metrics had been rejected previously as not valid species-distinguishing traits. In this respect, we do accept cranium size and wider palate as species-distinguishing metrics. The physical size of their specimens was much larger than other archaeological specimens that have been accepted as dogs. Additionally, their sample size was small, compared to the number of available specimens, as shown from previous publications by the same group. Thus, we considered statistical differences that were found between groups in their study, and assessed whether the outcomes could have resulted from natural morphological variation. We examined a group of 73 dire wolves ((Aenocyon [Canis] dirus; Perri et al., 2021), using the same methods as used by Galeta et al., (2020). We could segregate two distinct morphological groups in our study, one having outcomes that were identical to the "protodogs" in Galeta et al. (2020). For the specimens of extinct dire wolves to segregate in the same way as the subjects from Galeta et al. indicates that natural variation probably was the driver of their observed outcomes, domestication being an unlikely assumption.

Osteoarthritis from evolutionary and mechanistic perspectives.

Developmental osteogenesis and the pathologies associated with tissues that normally are mineralized are active areas of research. All of the basic cell types of skeletal tissue evolved in early aquatic vertebrates. Their characteristics, transcription factors, and signaling pathways have been conserved, even as they adapted to the challenge imposed by gravity in the transition to terrestrial existence. The response to excess mechanical stress (among other factors) can be expressed in the pathologic phenotype described as osteoarthritis (OA). OA is mediated by epigenetic modification of the same conserved developmental gene networks, rather than by gene mutations or new chemical signaling pathways. Thus, these responses have their evolutionary roots in morphogenesis. Epigenetic channeling and heterochrony, orchestrated primarily by microRNAs, maintain the sequence of these responses, while allowing variation in their timing that depends at least partly on the life history of the individual.

A Long-Term Lens: Cumulative Impacts of Free-Roaming Cat Management Strategy and Intensity on Preventable Cat Mortalities.

This study used a previously developed stochastic simulation model (1) to estimate the impact of different management actions on free-roaming kitten and cat mortality over a 10-year period. These longer-term cumulative impacts have not been systematically examined to date. We examined seven management scenarios, including: (1) taking no action, (2) low-intensity removal, (3) high-intensity removal, (4) low-intensity episodic culling, (5) high-intensity episodic culling, (6) low-intensity trap-neuter-return (TNR), and (7) high-intensity TNR. For each scenario we tracked within the model the number of kittens born, the number of kittens surviving to adulthood, and the number of adults removed using lethal control over the entire 10-year simulation. We further defined all kitten deaths and lethal removal of adults as "preventable" deaths because they could potentially be reduced by certain management actions. Our simulation results suggested that the cumulative number of preventable deaths over 10 years for an initial population of 50 cats is highest for a "no-action" scenario, estimated at 1,000 deaths. It is lowest for a high-intensity TNR scenario, estimated at 32 deaths, a 31-fold difference. For all management scenarios tested, including removal and culling, the model predicted fewer preventable deaths than for a no-action scenario. For all management scenarios, the model predicted that the higher-intensity option (defined in terms of the proportion of animals sterilized or removed within a given time period) would result in fewer preventable deaths over time than the lower-intensity option. Based on these findings, we conclude that management intensity is important not only to reduce populations more quickly, but also to minimize the number of preventable deaths that occur over time. Accordingly, the lessons for the animal welfare community are both encouraging and cautionary. With sufficient intensity, management by TNR offers significant advantages in terms of combined lifesaving and population size reduction. At lower intensity levels, these advantages are greatly reduced or eliminated. We recommend that those who seek to minimize suffering and maximize lifesaving for free-roaming cats attempt to balance prospective goals (i.e., saving lives tomorrow) with proximate goals (i.e., saving lives today), and recognize that thoughtful choice of management strategies can ensure that both of these complementary goals are achieved.

Suspected hypertrophic osteopathy in an ancient canid: Differential diagnosis of possible etiologies.

Hypertrophic osteopathy (HO) has been reported in numerous mammalian species, but no reports address the range of conditions that can lead to HO, or the implications of those conditions, for archaeological diagnosis. We describe suspected HO from skeletal remains of an ancient large domestic dog recovered in Iowa, USA, at the Cherokee Sewer site. Canid remains from this site date 7430-7020calBP. The site is believed to have been a temporary, low-intensity campsite where bison were procured. Over 100 specimens from two small dogs, two large dogs, and a coyote, are present in the archaeofaunal assemblage. We document five pathological metapodials; an affected left ulna, radius, tuber calcaneus, accessory carpal, radial carpal; and an affected right central, second, and third tarsal within in a proliferative mass. HO was suspected based on gross morphology, radiography, and computed tomography. HO is a paraneoplastic syndrome with undetermined underlying pathogenesis; neuroendocrine complication of a number of neoplastic and non-neoplastic diseases is suspected. We review known disease associations of HO to provide a balanced field for considering differential diagnosis of suspect archaeological specimens, and suggest that definitive diagnosis of HO, or suspected HO, may be impossible in many instances where only skeletal remains are available for study.

Simulating free-roaming cat population management options in open demographic environments.

Large populations of free-roaming cats (FRCs) generate ongoing concerns for welfare of both individual animals and populations, for human public health, for viability of native wildlife populations, and for local ecological damage. Managing FRC populations is a complex task, without universal agreement on best practices. Previous analyses that use simulation modeling tools to evaluate alternative management methods have focused on relative efficacy of removal (or trap-return, TR), typically involving euthanasia, and sterilization (or trap-neuter-return, TNR) in demographically isolated populations. We used a stochastic demographic simulation approach to evaluate removal, permanent sterilization, and two postulated methods of temporary contraception for FRC population management. Our models include demographic connectivity to neighboring untreated cat populations through natural dispersal in a metapopulation context across urban and rural landscapes, and also feature abandonment of owned animals. Within population type, a given implementation rate of the TR strategy results in the most rapid rate of population decline and (when populations are isolated) the highest probability of population elimination, followed in order of decreasing efficacy by equivalent rates of implementation of TNR and temporary contraception. Even low levels of demographic connectivity significantly reduce the effectiveness of any management intervention, and continued abandonment is similarly problematic. This is the first demographic simulation analysis to consider the use of temporary contraception and account for the realities of FRC dispersal and owned cat abandonment.

Chronology of hip dysplasia development in a cohort of 48 Labrador retrievers followed for life.

OBJECTIVE: To determine the chronology of radiographic signs of canine hip dysplasia (CHD), specifically joint laxity and secondary osteoarthritis (OA). STUDY DESIGN: Longitudinal cohort study. ANIMALS: Paired littermates, 48 Labrador retrievers. METHODS: Conventional, ventrodorsal, hip-extended (HE) radiographs were evaluated yearly for CHD according to the subjective criteria of the Orthopedic Foundation for Animals (OFA). PennHIP screening was performed at 2 years of age to assess joint laxity by distraction index (DI). Histopathologic evaluation of coxofemoral joints was performed at the dogs' natural end of life. RESULTS: Coxofemoral subluxation, as identified on the HE radiograph occurred by 2 years of age and not thereafter. Accuracy of OFA-criteria scoring was poor: 55% of dogs scored "normal" at 2 years of age became radiographically dysplastic by the end of life (45% negative predictive value, NPV); 92% of the dogs scored as normal at 2 years of age had histopathologic OA of CHD (8% NPV). The DI predicted all 48 dogs to be susceptible to OA of CHD and 98% had radiographic or histopathologic OA by the end of life. CONCLUSION: OFA-criteria score was profoundly influenced by environmental factors, such as diet restriction and age, reducing its value as a selection criterion. DI measurements were not influenced by dietary treatment suggesting higher trait heritability.

Lessons from a non-domestic canid: joint disease in captive raccoon dogs (Nyctereutes procyonoides).

The purpose of this study was to describe pathological changes of the shoulder, elbow, hip and stifle joints of 16 museum skeletons of the raccoon dog (Nyctereutes procyonoides). The subjects had been held in long-term captivity and were probably used for fur farming or research, thus allowing sufficient longevity for joint disease to become recognisable. The prevalence of disorders that include osteochondrosis, osteoarthritis and changes compatible with hip dysplasia, was surprisingly high. Other changes that reflect near-normal or mild pathological conditions, including prominent articular margins and mild bony periarticular rim, were also prevalent. Our data form a basis for comparing joint pathology of captive raccoon dogs with other mammals and also suggest that contributing roles of captivity and genetic predisposition should be explored further in non-domestic canids.

The changing understanding of ageing. Part 1: Evaluating ageing theories and studies.

This is the first of three discussions on emerging views of ageing, its derivation, and ageing-related diseases. To offer a context for the series, this first report briefly reviews several major early and recent theoretical debates. Arguments for and against several well-known ageing theories are presented for their veterinary relevance, including mutation, pleiotropy, reproduction-longevity trade-offs, oxygen metabolism and ageing as a genomically programmed product of natural selection. Additionally, the author presents commonly encountered problems when reading to interpret laboratory and population studies of ageing, offering busy clinicians a perspective on evaluating complex papers that analyse ageing-related data. Included among these problems are categorising intrinsic and extrinsic diseases, contrasts between laboratory-based and population-based observations, over-generalising research outcomes, short-term and long-term studies, and theoretical treatises. Central ideas of these discussions include why post-reproductive life span is relatively common among animals, the nature of age-related diseases relative to stochastic or programmed origins and the disease-related implications.

The changing understanding of ageing. Part 2: Body composition, metabolism and cell death.

This second of three discussions about ageing biology and diseases continues at the level of the organism, examining the relationship among body composition, late life and diseases. One view of significant age-related mass loss in humans suggests that anabolic failure is associated with various precipitating factors that may share anorexia in common. Lean mass decline with even partial anorexia should alert clinicians to monitor patients for emergence of otherwise subclinical disease. Weight or mass loss and clinical disease also may be independent, thus creating an interwoven and complex view. Recent data from the Portuguese water dog genetics model suggest that heritable factors play a role in end of life body metrics and some histological changes, and that some metric and histological changes are themselves inter-related. While widespread inflammation and hyperplasia were less frequent than expected, there exists nonetheless a disease relationship to the growth hormone (GH)-insulin-like growth factor (IGF-1)-insulin axis that requires further exploration. Oxidative metabolism and apoptosis are reviewed briefly as examples at the cellular level that may be reflected in gross ageing phenotypes, further underscoring the complex nature of many late-life diseases.

The changing understanding of ageing. Part 3: Diseases of ageing.

This third and final paper in this series considers ageing mechanisms across species, with emphasis on conserved metabolic pathways that relate to disease. The growth hormone (GH)-insulin-like growth factor (IGF-1)-insulin axis continues as an example of how critical pathways might relate to longevity and senescence. Aligning theory, research outcomes and clinical investigations at the levels of the cell, organism and population, is suggested as a means by which to consider the many complexities of the ageing process in an orderly fashion. A contentious debate revolves around whether ageing is purely a combined effect of stochastic events on residual programming relating to reproductive robustness, or whether ageing itself is programmed by natural selection. Emerging data indicate that the influence of genetic programming on specific late-life diseases, and even individual tissue pathologies, will probably need to be reconsidered in the light of newer theoretical possibilities. In particular, the evidence that late life and its diseases are objects of considerable investment of energy challenges theory that couples longevity with reproduction. Furthermore, the author suggests that ageing may have evolved at least partly as a means of niche preservation for contemporaries and for progeny.

Age relationships of postmortem observations in Portuguese Water Dogs.

A dog model has been used to evaluate histological changes arising from senescence. Autopsies of 145 Portuguese Water Dogs have been used to evaluate the individual and group "state of health" at time of death. For each dog, weights or dimensions of organs or tissues were obtained, together with histological evaluation of tissues. Twenty-three morphological metrics correlated significantly to age at death. Many of these involved muscles; others were associated with derivatives of embryonic foregut. The latter included lengths of the small intestine and trachea as well as weights of the stomach and some lung lobes. Nearly all of the dogs examined had histological changes in multiple tissues, ranging from two to 12 per dog. Associations among pathologies included inflammatory bowel disease with osteoporosis and dental calculus/periodontitis with atherosclerosis and amyloidosis. In addition, two clusters of histological changes were correlated to aging: hyperplasia, frequency of adenomas, and hemosiderosis constituted one group; inflammation, plasmacytic and lymphocytic infiltration, fibrosis, and atrophy, another. Heritability analysis indicated that many of the changes in tissue/organ morphology or histology could be heritable and possibly associated with IGF1, but more autopsies will be required to substantiate these genetic relationships.

Un-united medial epicondyle of the humerus: radiographic prevalence and association with elbow osteoarthritis in a cohort of labrador retrievers.

OBJECTIVE: To longitudinally characterize the radiographic appearance of un-united medial epicondyle (UME) of the humerus, evaluate UME association with osteoarthritis (OA) and consider its relevance to the elbow dysplasia complex. STUDY DESIGN: Longitudinal cohort study. ANIMALS: Labrador retrievers (n=48) from 7 litters. METHODS: Forty-eight same-sex littermates were paired for this lifetime feeding study. One of each pair was control-fed; the pair mate was fed 25% less than the control each day. Elbows of 46 surviving dogs were radiographed at ages 6 and 8 years, and/or at end-of-life (EOL). Elbow histopathology was done EOL, although UME lesions were not evaluated histologically. RESULTS: Seven dogs (15%) had UME, representing 5 litters; 4 were control-fed, 3 diet-restricted. Six (86%) dogs had unilateral lesions; 1 was bilateral. UME was evident on craniocaudal (CrCd) radiographic projections by 8 years in all dogs. UME was detected in only 1 elbow by mediolateral radiographic projection. Elbow OA frequency in UME affected dogs was not significantly different from the remaining study population. Histopathologic lesions were bilateral in dogs with unilateral UME. CONCLUSIONS: UME may be more common than previously thought. Most cases were unilateral and diet restriction had no effect on frequency. The CrCd view was critical for diagnosis. Elbow OA was not directly associated with UME. CLINICAL RELEVANCE: Infrequent diagnosis of UME could result from infrequent radiography and use of only the flexed lateral radiographic projection required by the Orthopedic Foundation for Animals for elbow screening. Like hip evaluations, screening for UME should be continued for life, until genetics are better understood. Lack of association between UME and elbow OA suggests that UME is not likely a component of elbow dysplasia.

A longitudinal study of the influence of lifetime food restriction on development of osteoarthritis in the canine elbow.

OBJECTIVE: To report the effects of age and lifetime calorie restriction on development and progression of osteoarthritis (OA) in elbow joints of Labrador retrievers. STUDY DESIGN: Longitudinal cohort study. ANIMALS: Labrador retriever dogs (n=48). METHODS: Puppies from 7 litters were allotted to 2 groups of 24 dogs each. Diet-restricted (DR) dogs received 25% fewer calories than control-fed (CF) pair mates. Elbow radiographs were taken at 6 and 8 years of age and end of life (EOL). Gross and histopathologic evaluations for OA occurred at EOL. RESULTS: There was no statistical difference in radiographic OA frequency between groups at any of the time points. Radiographic OA severity was greater for CF dogs at 6 years only (P<.05). There was no significant difference between feeding groups for histopathologic prevalence or severity of OA. Similarly, there were no differences in gross OA lesions between the groups (P>.05). Fragmented medial coronoid process, un-united anconeal process, and osteochondrosis were not present in any elbow. CONCLUSION: No differences in prevalence or severity of radiographic and histopathologic elbow OA were found between feeding groups. Diet restriction resulted in a 1.8-year extension in median lifespan but no additional incremental worsening of elbow disease. Evaluation at time points <6 years may have revealed larger differences in OA prevalence and severity between the dietary groups. CLINICAL RELEVANCE: These findings support calorie restriction as a clinical tool to slow progression of elbow OA.

Exploring human/animal intersections: converging lines of evidence in comparative models of aging.

At a symposium convened on March 8, 2007 by the Institute on Aging at the University of Pennsylvania, researchers from the University's Schools of Medicine and Veterinary Medicine explored the convergence of aging research emerging from the two schools. Studies in human patients, animal models, and companion animals have revealed different but complementary aspects of the aging process, ranging from fundamental biologic aspects of aging to the treatment of age-related diseases, both experimentally and in clinical practice. Participants concluded that neither animal nor human research alone will provide answers to most questions about the aging process. Instead, an optimal translational research model supports a bidirectional flow of information from animal models to clinical research.