Quantifying the relationship between bone and soft tissue measures within the rhesus macaques of Cayo Santiago.

OBJECTIVES: Interpretations of the primate and human fossil record often rely on the estimation of somatic dimensions from bony measures. Both somatic and skeletal variation have been used to assess how primates respond to environmental change. However, it is unclear how well skeletal variation matches and predicts soft tissue. Here, we empirically test the relationship between tissues by comparing somatic and skeletal measures using paired measures of pre- and post-mortem rhesus macaques from Cayo Santiago, Puerto Rico. MATERIALS AND METHODS: Somatic measurements were matched with skeletal dimensions from 105 rhesus macaque individuals to investigate paired signals of variation (i.e., coefficients of variation, sexual dimorphism) and bivariate codependence (reduced major axis regression) in measures of: (1) limb length; (2) joint breadth; and (3) limb circumference. Predictive models for the estimation of soft tissue dimensions from skeletons were built from Ordinary Least Squares regressions. RESULTS: Somatic and skeletal measurements showed statistically equivalent coefficients of variation and sexual dimorphism as well as high epiphyses-present ordinary least square (OLS) correlations in limb lengths (R2 >0.78, 0.82), joint breadths (R2 >0.74, 0.83) and, to a lesser extent, limb circumference (R2 >0.53, 0.68). CONCLUSION: Skeletal measurements are good substitutions for somatic values based on population signals of variation. OLS regressions indicate that skeletal correlates are highly predictive of somatic dimensions. The protocols and regression equations established here provide a basis for reliable reconstruction of somatic dimension from catarrhine fossils and validate our ability to compare or combine results of studies based on population data of either hard or soft tissue proxies.

Mechanical and morphometric approaches to body mass estimation in rhesus macaques: A test of skeletal variables.

OBJECTIVES: Estimation of body mass from skeletal metrics can reveal important insights into the paleobiology of archeological or fossil remains. The standard approach constructs predictive equations from postcrania, but studies have questioned the reliability of traditional measures. Here, we examine several skeletal features to assess their accuracy in predicting body mass. MATERIALS AND METHODS: Antemortem mass measurements were compared with common skeletal dimensions from the same animals postmortem, using 115 rhesus macaques (male: n = 43; female: n = 72). Individuals were divided into training (n = 58) and test samples (n = 57) to build and assess Ordinary Least Squares or multivariate regressions by residual sum of squares (RSS) and AIC weights. A leave-one-out approach was implemented to formulate the best fit multivariate models, which were compared against a univariate and a previously published catarrhine body-mass estimation model. RESULTS: Femur circumference represented the best univariate model. The best model overall was composed of four variables (femur, tibia and fibula circumference and humerus length). By RSS and AICw, models built from rhesus macaque data (RSS = 26.91, AIC = -20.66) better predicted body mass than did the catarrhine model (RSS = 65.47, AIC = 20.24). CONCLUSION: Body mass in rhesus macaques is best predicted by a 4-variable equation composed of humerus length and hind limb midshaft circumferences. Comparison of models built from the macaque versus the catarrhine data highlight the importance of taxonomic specificity in predicting body mass. This paper provides a valuable dataset of combined somatic and skeletal data in a primate, which can be used to build body mass equations for fragmentary fossil evidence.

Covariation between the shape and mineralized tissues of the rib cross section in Homo sapiens, Pan troglodytes and Sts 14.

OBJECTIVES: Studying rib torsion is crucial for understanding the evolution of the hominid ribcage. Interestingly, there are variables of the rib cross section that could be associated with rib torsion and, consequently, with the morphology of the thorax. The aim of this research is to conduct a comparative study of the shape and mineralized tissues of the rib cross section in different hominids to test for significant differences and, if possible, associate them to different thoracic morphotypes. MATERIALS AND METHODS: The sample consists of the rib cross sections at the midshaft taken from 10 Homo sapiens and 10 Pan troglodytes adult individuals, as well as from A. africanus Sts 14. The shape of these rib cross sections was quantified using geometric morphometrics, while the mineralized tissues were evaluated using the compartmentalization index. Subsequently, covariation between both parameters was tested by a Spearman's ρ test, a permutation test and a linear regression. RESULTS: Generally, P. troglodytes individuals exhibit rib cross sections that are rounder and more mineralized compared to those of H. sapiens. However, the covariation between both parameters was only observed in typical ribs (levels 3-10). Although covariation was not found in the rib cross sections of Sts 14, their parameters are closer to P. troglodytes. DISCUSSION: On the one hand, the differences observed in the rib cross sections between H. sapiens and P. troglodytes might be related to different degrees of rib torsion and, consequently, to different thoracic 3D configurations. These findings can be functionally explained by considering their distinct modes of breathing and locomotion. On the other hand, although the rib cross sections belonging to Sts 14 are more similar to those of P. troglodytes, previous publications determined that their overall morphology is closer to modern humans. This discrepancy could reflect a diversity of post-cranial adaptations in Australopithecus.

Morphological and evolutionary insights into the keystone element of the human foot's medial longitudinal arch.

The evolution of the medial longitudinal arch (MLA) is one of the most impactful adaptations in the hominin foot that emerged with bipedalism. When and how it evolved in the human lineage is still unresolved. Complicating the issue, clinical definitions of flatfoot in living Homo sapiens have not reached a consensus. Here we digitally investigate the navicular morphology of H. sapiens (living, archaeological, and fossil), great apes, and fossil hominins and its correlation with the MLA. A distinctive navicular shape characterises living H. sapiens with adult acquired flexible flatfoot, while the congenital flexible flatfoot exhibits a 'normal' navicular shape. All H. sapiens groups differentiate from great apes independently from variations in the MLA, likely because of bipedalism. Most australopith, H. naledi, and H. floresiensis navicular shapes are closer to those of great apes, which is inconsistent with a human-like MLA and instead might suggest a certain degree of arboreality. Navicular shape of OH 8 and fossil H. sapiens falls within the normal living H. sapiens spectrum of variation of the MLA (including congenital flexible flatfoot and individuals with a well-developed MLA). At the same time, H. neanderthalensis seem to be characterised by a different expression of the MLA.

Evolution of vertebral numbers in primates, with a focus on hominoids and the last common ancestor of hominins and panins.

The primate vertebral column has been extensively studied, with a particular focus on hominoid primates and the last common ancestor of humans and chimpanzees. The number of vertebrae in hominoids-up to and including the last common ancestor of humans and chimpanzees-is subject to considerable debate. However, few formal ancestral state reconstructions exist, and none include a broad sample of primates or account for the correlated evolution of the vertebral column. Here, we conduct an ancestral state reconstruction using a model of evolution that accounts for both homeotic (changes of one type of vertebra to another) and meristic (addition or loss of a vertebra) changes. Our results suggest that ancestral primates were characterized by 29 precaudal vertebrae, with the most common formula being seven cervical, 13 thoracic, six lumbar, and three sacral vertebrae. Extant hominoids evolved tail loss and a reduced lumbar column via sacralization (homeotic transition at the last lumbar vertebra). Our results also indicate that the ancestral hylobatid had seven cervical, 13 thoracic, five lumbar, and four sacral vertebrae, and the ancestral hominid had seven cervical, 13 thoracic, four lumbar, and five sacral vertebrae. The last common ancestor of humans and chimpanzees likely either retained this ancestral hominid formula or was characterized by an additional sacral vertebra, possibly acquired through a homeotic shift at the sacrococcygeal border. Our results support the 'short-back' model of hominin vertebral evolution, which postulates that hominins evolved from an ancestor with an African ape-like numerical composition of the vertebral column.

Knuckle-walking in Sahelanthropus? Locomotor inferences from the ulnae of fossil hominins and other hominoids.

Because the ulna supports and transmits forces during movement, its morphology can signal aspects of functional adaptation. To test whether, like extant apes, some hominins habitually recruit the forelimb in locomotion, we separate the ulna shaft and ulna proximal complex for independent shape analyses via elliptical Fourier methods to identify functional signals. We examine the relative influence of locomotion, taxonomy, and body mass on ulna contours in Homo sapiens (n = 22), five species of extant apes (n = 33), two Miocene apes (Hispanopithecus and Danuvius), and 17 fossil hominin specimens including Sahelanthropus, Ardipithecus, Australopithecus, Paranthropus, and early Homo. Ulna proximal complex contours correlate with body mass but not locomotor patterns, while ulna shafts significantly correlate with locomotion. African apes' ulna shafts are more robust and curved than Asian apes and are unlike other terrestrial mammals (including other primates), curving ventrally rather than dorsally. Because this distinctive curvature is absent in orangutans and hylobatids, it is likely a function of powerful flexors engaged in wrist and hand stabilization during knuckle-walking, and not an adaptation to climbing or suspensory behavior. The OH 36 (purported Paranthropus boisei) and TM 266 (assigned to Sahelanthropus tchadensis) fossils differ from other hominins by falling within the knuckle-walking morphospace, and thus appear to show forelimb morphology consistent with terrestrial locomotion. Discriminant function analysis classifies both OH 36 and TM 266 with Pan and Gorilla with high posterior probability. Along with its associated femur, the TM 266 ulna shaft contours and its deep, keeled trochlear notch comprise a suite of traits signaling African ape-like quadrupedalism. While implications for the phylogenetic position and hominin status of S. tchadensis remain equivocal, this study supports the growing body of evidence indicating that S. tchadensis was not an obligate biped, but instead represents a late Miocene hominid with knuckle-walking adaptations.

Crocodile defensin (CpoBD13) antifungal activity via pH-dependent phospholipid targeting and membrane disruption.

Crocodilians are an order of ancient reptiles that thrive in pathogen-rich environments. The ability to inhabit these harsh environments is indicative of a resilient innate immune system. Defensins, a family of cysteine-rich cationic host defence peptides, are a major component of the innate immune systems of all plant and animal species, however crocodilian defensins are poorly characterised. We now show that the saltwater crocodile defensin CpoBD13 harbors potent antifungal activity that is mediated by a pH-dependent membrane-targeting action. CpoBD13 binds the phospholipid phosphatidic acid (PA) to form a large helical oligomeric complex, with specific histidine residues mediating PA binding. The utilisation of histidine residues for PA engagement allows CpoBD13 to exhibit differential activity at a range of environmental pH values, where CpoBD13 is optimally active in an acidic environment.

Novel Formulation of Undecylenic Acid induces Tumor Cell Apoptosis.

Undecylenic acid, a monounsaturated fatty acid, is currently in clinical use as a topical antifungal agent, however the potential for therapeutic application in other disease settings has not been investigated. In this study, we describe a novel platform for the solubilization of fatty acids using amino acids and utilize this approach to define a tumoricidal activity and underlying mechanism for undecylenic acid. We examined a novel formulation of undecylenic acid compounded with L-Arginine, called GS-1, that induced concentration-dependent tumor cell death, with undecylenic acid being the cytotoxic component. Further investigation revealed that GS-1-mediated cell death was caspase-dependent with a reduction in mitochondrial membrane potential, suggesting a pro-apoptotic mechanism of action. Additionally, GS-1 was found to localize intracellularly to lipid droplets. In contrast to previous studies where lipid droplets have been shown to be protective against fatty acid-induced cell death, we showed that lipid droplets could not protect against GS-1-induced cytotoxicity. We also found a role for Fatty Acid Transport Protein 2 (FATP2) in the uptake of this compound. Collectively, this study demonstrates that GS-1 has effective pro-apoptotic antitumor activity in vitro and, together with the novel platform of fatty acid solubilization, contributes to the re-emerging field of fatty acids as potential anti-cancer therapeutics.

The ontogeny of sexual dimorphism in free-ranging rhesus macaques.

Objective: Reconstructing the social lives of extinct primates is possible only through an understanding of the interplay between morphology, sexual selection pressures, and social behavior in extant species. Somatic sexual dimorphism is an important variable in primate evolution, in part because of the clear relationship between the strength and mechanisms of sexual selection and the degree of dimorphism. Here, we examine body size dimorphism across ontogeny in male and female rhesus macaques to assess whether it is primarily achieved via bimaturism as predicted by a polygynandrous mating system, faster male growth indicating polygyny, or both. Methods: We measured body mass in a cross-sectional sample of 364 free-ranging rhesus macaques from Cayo Santiago, Puerto Rico to investigate size dimorphism: 1) across the lifespan; and 2) as an outcome of sex-specific growth strategies, including: a) age of maturation; b) growth rate; and c) total growth duration, using regression models fit to sex-specific developmental curves. Results: Significant body size dimorphism was observed by prime reproductive age with males 1.51 times the size of females. Larger male size resulted from a later age of maturation (males: 6.8-7.8 years versus females: 5.5-6.5 years; logistic model) and elevated growth velocity through the pre-prime period (LOESS model). Though males grew to larger sizes overall, females maintained adult size for longer before senescence (quadratic model). Discussion: The ontogeny of size dimorphism in rhesus macaques is achieved by bimaturism and a faster male growth rate. Our results provide new data for understanding the development and complexities of primate dimorphism.

Human ß-Defensin 2 (HBD-2) Displays Oncolytic Activity but Does Not Affect Tumour Cell Migration.

Defensins form an integral part of the cationic host defence peptide (HDP) family, a key component of innate immunity. Apart from their antimicrobial and immunomodulatory activities, many HDPs exert multifaceted effects on tumour cells, notably direct oncolysis and/or inhibition of tumour cell migration. Therefore, HDPs have been explored as promising anticancer therapeutics. Human ß-defensin 2 (HBD-2) represents a prominent member of human HDPs, being well-characterised for its potent pathogen-killing, wound-healing, cytokine-inducing and leukocyte-chemoattracting functions. However, its anticancer effects remain largely unknown. Recently, we demonstrated that HBD-2 binds strongly to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), a key mediator of defensin-induced cell death and an instructional messenger during cell migration. Hence, in this study, we sought to investigate the lytic and anti-migratory effects of HBD-2 on tumour cells. Using various cell biological assays and confocal microscopy, we showed that HBD-2 killed tumour cells via acute lytic cell death rather than apoptosis. In addition, our data suggested that, despite the reported PI(4,5)P2 interaction, HBD-2 does not affect cytoskeletal-dependent tumour cell migration. Together, our findings provide further insights into defensin biology and informs future defensin-based drug development.

Inferring lumbar lordosis in Neandertals and other hominins.

Lumbar lordosis is a key adaptation to bipedal locomotion in the human lineage. Dorsoventral spinal curvatures enable the body's center of mass to be positioned above the hip, knee, and ankle joints, and minimize the muscular effort required for postural control and locomotion. Previous studies have suggested that Neandertals had less lordotic (ventrally convex) lumbar columns than modern humans, which contributed to historical perceptions of postural and locomotor differences between the two groups. Quantifying lower back curvature in extinct hominins is entirely reliant upon bony correlates of overall lordosis, since the latter is significantly influenced by soft tissue structures (e.g. intervertebral discs). Here, we investigate sexual dimorphism, ancestry, and lifestyle effects on lumbar vertebral body wedging and inferior articular facet angulation, two features previously shown to be significantly correlated with overall lordosis in living individuals, in a large sample of modern humans and Neandertals. Our results demonstrate significant differences between postindustrial cadaveric remains and archaeological samples of people that lived preindustrial lifestyles. We suggest these differences are related to activity and other aspects of lifestyle rather than innate population (ancestry) differences. Neandertal bony correlates of lumbar lordosis are significantly different from all human samples except preindustrial males. Therefore, although Neandertals demonstrate more bony kyphotic wedging than most modern humans, we cast doubt on proposed locomotor and postural differences between the two lineages based on inferred lumbar lordosis (or lack thereof), and we recommend future research compare fossils to modern humans from varied populations and not just recent, postindustrial samples.

New fossils of Australopithecus sediba reveal a nearly complete lower back.

Adaptations of the lower back to bipedalism are frequently discussed but infrequently demonstrated in early fossil hominins. Newly discovered lumbar vertebrae contribute to a near-complete lower back of Malapa Hominin 2 (MH2), offering additional insights into posture and locomotion in Australopithecus sediba. We show that MH2 possessed a lower back consistent with lumbar lordosis and other adaptations to bipedalism, including an increase in the width of intervertebral articular facets from the upper to lower lumbar column ('pyramidal configuration'). These results contrast with some recent work on lordosis in fossil hominins, where MH2 was argued to demonstrate no appreciable lordosis ('hypolordosis') similar to Neandertals. Our three-dimensional geometric morphometric (3D GM) analyses show that MH2's nearly complete middle lumbar vertebra is human-like in overall shape but its vertebral body is somewhat intermediate in shape between modern humans and great apes. Additionally, it bears long, cranially and ventrally oriented costal (transverse) processes, implying powerful trunk musculature. We interpret this combination of features to indicate that A. sediba used its lower back in both bipedal and arboreal positional behaviors, as previously suggested based on multiple lines of evidence from other parts of the skeleton and reconstructed paleobiology of A. sediba.

One of the defining features of humans is our ability to walk comfortably on two legs. To achieve this, our skeletons have evolved certain physical characteristics. For example, the lower part of the human spine has a forward curve that supports an upright posture; whereas the lower backs of chimpanzees and other apes ­ which walk around on four limbs and spend much of their time in trees ­ lack this curvature. Studying the fossilized back bones of ancient human remains can help us to understand how we evolved these features, and whether our ancestors moved in a similar way. Australopithecus sediba was a close-relative of modern humans that lived about two million years ago. In 2008, fossils from an adult female were discovered at a cave site in South Africa called Malapa. However, the fossils of the lower back region were incomplete, so it was unclear whether the female ­ referred to as Malapa Hominin 2 (MH2) ­ had a forward-curving spine and other adaptations needed to walk on two legs. Here, Williams et al. report the discovery of new A. sediba fossils from Malapa. The new fossils are mainly bones from the lower back, and they fit together with the previously discovered MH2 fossils, providing a nearly complete lower spine. Analysis of the fossils suggested that MH2 would have had an upright posture and comfortably walked on two legs, and the curvature of their lower back was similar to modern females. However, other aspects of the bones' shape suggest that as well as walking, A. sediba probably spent a significant amount of time climbing in trees. The findings of Williams et al. provide new insights in to our evolutionary history, and ultimately, our place in the natural world around us. Our lower back is prone to injury and pain associated with posture, pregnancy and exercise (or lack thereof). Therefore, understanding how the lower back evolved may help us to learn how to prevent injuries and maintain a healthy back.

Homeotic change in segment identity derives the human vertebral formula from a chimpanzee-like one.

OBJECTIVES: One of the most contentious issues in paleoanthropology is the nature of the last common ancestor of humans and our closest living relatives, chimpanzees and bonobos (panins). The numerical composition of the vertebral column has featured prominently, with multiple models predicting distinct patterns of evolution and contexts from which bipedalism evolved. Here, we study total numbers of vertebrae from a large sample of hominoids to quantify variation in and patterns of regional and total numbers of vertebrae in hominoids. MATERIALS AND METHODS: We compile and study a large sample (N = 893) of hominoid vertebral formulae (numbers of cervical, thoracic, lumbar, sacral, caudal segments in each specimen) and analyze full vertebral formulae, total numbers of vertebrae, and super-regional numbers of vertebrae: presacral (cervical, thoracic, lumbar) vertebrae and sacrococcygeal vertebrae. We quantify within- and between-taxon variation using heterogeneity and similarity measures derived from population genetics. RESULTS: We find that humans are most similar to African apes in total and super-regional numbers of vertebrae. Additionally, our analyses demonstrate that selection for bipedalism reduced variation in numbers of vertebrae relative to other hominoids. DISCUSSION: The only proposed ancestral vertebral configuration for the last common ancestor of hominins and panins that is consistent with our results is the modal formula demonstrated by chimpanzees and bonobos (7 cervical-13 thoracic-4 lumbar-6 sacral-3 coccygeal). Hox gene expression boundaries suggest that a rostral shift in Hox10/Hox11-mediated complexes could produce the human modal formula from the proposal ancestral and panin modal formula.

Homoplasy in the evolution of modern human-like joint proportions in Australopithecus afarensis.

The evolution of bipedalism and reduced reliance on arboreality in hominins resulted in larger lower limb joints relative to the joints of the upper limb. The pattern and timing of this transition, however, remains unresolved. Here, we find the limb joint proportions of Australopithecus afarensis, Homo erectus, and Homo naledi to resemble those of modern humans, whereas those of A. africanus, Australopithecus sediba, Paranthropus robustus, Paranthropus boisei, Homo habilis, and Homo floresiensis are more ape-like. The homology of limb joint proportions in A. afarensis and modern humans can only be explained by a series of evolutionary reversals irrespective of differing phylogenetic hypotheses. Thus, the independent evolution of modern human-like limb joint proportions in A. afarensis is a more parsimonious explanation. Overall, these results support an emerging perspective in hominin paleobiology that A. afarensis was the most terrestrially adapted australopith despite the importance of arboreality throughout much of early hominin evolution.

Ardipithecus hand provides evidence that humans and chimpanzees evolved from an ancestor with suspensory adaptations.

The morphology and positional behavior of the last common ancestor of humans and chimpanzees are critical for understanding the evolution of bipedalism. Early 20th century anatomical research supported the view that humans evolved from a suspensory ancestor bearing some resemblance to apes. However, the hand of the 4.4-million-year-old hominin Ardipithecus ramidus purportedly provides evidence that the hominin hand was derived from a more generalized form. Here, we use morphometric and phylogenetic comparative methods to show that Ardipithecus retains suspensory adapted hand morphologies shared with chimpanzees and bonobos. We identify an evolutionary shift in hand morphology between Ardipithecus and Australopithecus that renews questions about the coevolution of hominin manipulative capabilities and obligate bipedalism initially proposed by Darwin. Overall, our results suggest that early hominins evolved from an ancestor with a varied positional repertoire including suspension and vertical climbing, directly affecting the viable range of hypotheses for the origin of our lineage.

Rib cage anatomy in Homo erectus suggests a recent evolutionary origin of modern human body shape.

The tall and narrow body shape of anatomically modern humans (Homo sapiens) evolved via changes in the thorax, pelvis and limbs. It is debated, however, whether these modifications first evolved together in African Homo erectus, or whether H. erectus had a more primitive body shape that was distinct from both the more ape-like Australopithecus species and H. sapiens. Here we present the first quantitative three-dimensional reconstruction of the thorax of the juvenile H. erectus skeleton, KNM-WT 15000, from Nariokotome, Kenya, along with its estimated adult rib cage, for comparison with H. sapiens and the Kebara 2 Neanderthal. Our three-dimensional reconstruction demonstrates a short, mediolaterally wide and anteroposteriorly deep thorax in KNM-WT 15000 that differs considerably from the much shallower thorax of H. sapiens, pointing to a recent evolutionary origin of fully modern human body shape. The large respiratory capacity of KNM-WT 15000 is compatible with the relatively stocky, more primitive, body shape of H. erectus.

Variation in mouse pelvic morphology maps to locations enriched in Sox9 Class II and Pitx1 regulatory features.

Variation in pelvic morphology has a complex genetic basis and its patterning and specification is governed by conserved developmental pathways. Whether the mechanisms underlying the differentiation and specification of the pelvis also produce the morphological covariation on which natural selection may act, is still an open question in evolutionary developmental biology. We use high-resolution quantitative trait locus (QTL) mapping in the F34 generation of an advanced intercross experiment (LG,SM-G34 ) to characterize the genetic architecture of the mouse pelvis. We test the prediction that genomic features linked to developmental patterning and differentiation of the hind limb and pelvis and the regulation of chondrogenesis are overrepresented in QTL. We find 31 single QTL trait associations at the genome- or chromosome-wise significance level coalescing to 27 pleiotropic loci. We recover further QTL at a more relaxed significance threshold replicating locations found in a previous experiment in an earlier generation of the same population. QTL were more likely than chance to harbor Pitx1 and Sox9 Class II chromatin immunoprecipitation-seq features active during development of skeletal features. There was weak or no support for the enrichment of seven more categories of developmental features drawn from the literature. Our results suggest that genotypic variation is channeled through a subset of developmental processes involved in the generation of phenotypic variation in the pelvis. This finding indicates that the evolvability of complex traits may be subject to biases not evident from patterns of covariance among morphological features or developmental patterning when either is considered in isolation.

Growing up Tyrannosaurus rex: Osteohistology refutes the pygmy "Nanotyrannus" and supports ontogenetic niche partitioning in juvenile Tyrannosaurus.

Despite its iconic status as the king of dinosaurs, Tyrannosaurus rex biology is incompletely understood. Here, we examine femur and tibia bone microstructure from two half-grown T. rex specimens, permitting the assessments of age, growth rate, and maturity necessary for investigating the early life history of this giant theropod. Osteohistology reveals these were immature individuals 13 to 15 years of age, exhibiting growth rates similar to extant birds and mammals, and that annual growth was dependent on resource abundance. Together, our results support the synonomization of "Nanotyrannus" into Tyrannosaurus and fail to support the hypothesized presence of a sympatric tyrannosaurid species of markedly smaller adult body size. Our independent data contribute to mounting evidence for a rapid shift in body size associated with ontogenetic niche partitioning late in T. rex ontogeny and suggest that this species singularly exploited mid- to large-sized theropod niches at the end of the Cretaceous.

Combating Human Pathogens and Cancer by Targeting Phosphoinositides and Their Metabolism.

Pathogens and tumor cells have adopted various adept strategies to evade immunosurveillance and promote their growth and survival. There has been substantial evidence demonstrating phosphoinositide lipids and their modifying enzymes as essential host targets that are often hijacked by pathogens and tumor cells. The common dependence of pathogen virulence and tumor progression on phosphoinositides presents an exciting disease-combating potential, particularly combinatorial therapeutics. While traditional approaches to pharmacologically inhibit phosphoinositide-metabolizing enzymes has shown some promise, the direct targeting of phosphoinositides has recently emerged as a novel therapeutic strategy. Our review provides a current picture of the role of phosphoinositides during pathogen virulence and tumorigenesis as well as a thorough discussion on promises, challenges, and new perspectives of phosphoinositide-targeting drug development.