Alveolar type I cells can give rise to KRAS-induced lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer and presents clinically with a high degree of biological heterogeneity and distinct clinical outcomes. The current paradigm of LUAD etiology posits alveolar epithelial type II (AT2) cells as the primary cell of origin, while the role of AT1 cells in LUAD oncogenesis remains unknown. Here, we examine oncogenic transformation in mouse Gram-domain containing 2 (Gramd2)+ AT1 cells via oncogenic KRASG12D. Activation of KRASG12D in AT1 cells induces multifocal LUAD, primarily of papillary histology. Furthermore, KRT8+ intermediate cell states were observed in both AT2- and AT1-derived LUAD, but SCGB3A2+, another intermediate cell marker, was primarily associated with AT1 cells, suggesting different mechanisms of tumor evolution. Collectively, our study reveals that Gramd2+ AT1 cells can serve as a cell of origin for LUAD and suggests that distinct subtypes of LUAD based on cell of origin be considered in the development of therapeutics.

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.

Effects of the energy balance transition on bone mass and strength.

Chronic positive energy balance has surged among societies worldwide due to increasing dietary energy intake and decreasing physical activity, a phenomenon called the energy balance transition. Here, we investigate the effects of this transition on bone mass and strength. We focus on the Indigenous peoples of New Mexico in the United States, a rare case of a group for which data can be compared between individuals living before and after the start of the transition. We show that since the transition began, bone strength in the leg has markedly decreased, even though bone mass has apparently increased. Decreased bone strength, coupled with a high prevalence of obesity, has resulted in many people today having weaker bones that must sustain excessively heavy loads, potentially heightening their risk of a bone fracture. These findings may provide insight into more widespread upward trends in bone fragility and fracture risk among societies undergoing the energy balance transition.

gp130/STAT3 signaling is required for homeostatic proliferation and anabolism in postnatal growth plate and articular chondrocytes.

Growth of long bones and vertebrae is maintained postnatally by a long-lasting pool of progenitor cells. Little is known about the molecular mechanisms that regulate the output and maintenance of the cells that give rise to mature cartilage. Here we demonstrate that postnatal chondrocyte-specific deletion of a transcription factor Stat3 results in severely reduced proliferation coupled with increased hypertrophy, growth plate fusion, stunting and signs of progressive dysfunction of the articular cartilage. This effect is dimorphic, with females more strongly affected than males. Chondrocyte-specific deletion of the IL-6 family cytokine receptor gp130, which activates Stat3, phenocopied Stat3-deletion; deletion of Lifr, one of many co-receptors that signals through gp130, resulted in a milder phenotype. These data define a molecular circuit that regulates chondrogenic cell maintenance and output and reveals a pivotal positive function of IL-6 family cytokines in the skeletal system with direct implications for skeletal development and regeneration.

Morphological description and evolutionary significance of 300 ka hominin facial bones from Hualongdong, China.

Late Middle Pleistocene hominins in Africa displaying key modern morphologies by 315 ka are claimed as the earliest Homo sapiens. Evolutionary relationships among East Asian hominins appear complex due to a growing fossil record of late Middle Pleistocene hominins from the region, reflecting mosaic morphologies that contribute to a lack of consensus on when and how the transition to modern humans transpired. Newly discovered 300 ka hominin fossils from Hualongdong, China, provide further evidence to clarify these relationships in the region. In this study, facial morphology of the juvenile partial cranium (HLD 6) is described and qualitatively and quantitatively compared with that of other key Early, Middle, and Late Pleistocene hominins from East Asia, Africa, West Asia, and Europe and with a sample of modern humans. Qualitatively, facial morphology of HLD 6 resembles that of Early and Middle Pleistocene hominins from Zhoukoudian, Nanjing, Dali, and Jinniushan in China, as well as others from Java, Africa, and Europe in some of these features (e.g., supraorbital and malar regions), and Late Pleistocene hominins and modern humans from East Asia, Africa, and Europe in other features (e.g., weak prognathism, flat face and features in nasal and hard plate regions). Comparisons of HLD 6 measurements to group means and multivariate analyses support close affinities of HLD 6 to Late Pleistocene hominins and modern humans. Expression of a mosaic morphological pattern in the HLD 6 facial skeleton further complicates evolutionary interpretations of regional morphological diversity in East Asia. The prevalence of modern features in HLD 6 suggests that the hominin population to which HLD 6 belonged may represent the earliest pre-modern humans in East Asia. Thus, the transition from archaic to modern morphology in East Asian hominins may have occurred at least by 300 ka, which is 80,000 to 100,000 years earlier than previously recognized.

StW 573 Australopithecus prometheus: Its Significance for an Australopith Bauplan.

The StW 573 skeleton of Australopithecus prometheus from Sterkfontein Member 2 is some 93% complete and thus by far the most complete member of that genus yet found. Firmly dated at 3.67 Ma, it is one of the earliest specimens of its genus. A crucial aspect of interpretation of locomotor behaviour from fossil remains is an understanding of the palaeoenvironment in which the individual lived and the manner in which it would have used it. While the value of this ecomorphological approach is largely accepted, it has not been widely used as a stable framework on which to build evolutionary biomechanical interpretations. Here, we collate the available evidence on StW 573's anatomy in order, as far as currently possible, to reconstruct what might have been this individual's realized and potential niche. We explore the concept of a common Australopithecus "bauplan" by comparing the morphology and ecological context of StW 573 to that of paenocontemporaneous australopiths including Australopithecus anamensis and KSD-VP-1/1 Australopithecus afarensis. Each was probably substantially arboreal and woodland-dwelling, relying substantially on arboreal resources. We use a hypothesis-driven approach, tested by: virtual experiments, in the case of extinct species; biomechanical analyses of the locomotor behaviour of living great ape species; and analogical experiments with human subjects. From these, we conclude that the habitual locomotor mode of all australopiths was upright bipedalism, whether on the ground or on branches. Some later australopiths such as Australopithecus sediba undoubtedly became more terrestrial, allowing sacrifice of arboreal stability in favour of manual dexterity. Indeed, modern humans retain arboreal climbing skills but have further sacrificed arboreal effectiveness for enhanced ability to sustain striding terrestrial bipedalism over much greater distances. We compare StW 573's locomotor adaptations to those of living great apes and protohominins, and agree with those earlier observers who suggest that the common panin-hominin last common ancestor was postcranially more like Gorilla than Pan.

The pectoral girdle of StW 573 ('Little Foot') and its implications for shoulder evolution in the Hominina.

The ca. 3.67 Ma adult skeleton known as 'Little Foot' (StW 573), recovered from Sterkfontein Member 2 breccia in the Silberberg Grotto, is remarkable for its morphology and completeness. Preservation of clavicles and scapulae, including essentially complete right-side elements, offers opportunities to assess morphological and functional aspects of a nearly complete Australopithecus pectoral girdle. Here we describe the StW 573 pectoral girdle and offer quantitative comparisons to those of extant hominoids and selected homininans. The StW 573 pectoral girdle combines features intermediate between those of humans and other apes: a long and curved clavicle, suggesting a relatively dorsally positioned scapula; an enlarged and uniquely proportioned supraspinous fossa; a relatively cranially oriented glenoid fossa; and ape-like reinforcement of the axillary margin by a stout ventral bar. StW 573 scapulae are as follows: smaller than those of some homininans (i.e., KSD-VP-1/1 and KNM-ER 47000A), larger than others (i.e., A.L. 288-1, Sts 7, and MH2), and most similar in size to another australopith from Sterkfontein, StW 431. Moreover, StW 573 and StW 431 exhibit similar structural features along their axillary margins and inferior angles. As the StW 573 pectoral girdle (e.g., scapular configuration) has a greater affinity to that of apes-Gorilla in particular-rather than modern humans, we suggest that the StW 573 morphological pattern appears to reflect adaptations to arboreal behaviors, especially those with the hand positioned above the head, more than human-like manipulatory capabilities. When compared with less complete pectoral girdles from middle/late Miocene apes and that of the penecontemporaneous KSD-VP-1/1 (Australopithecus afarensis), and mindful of consensus views on the adaptiveness of arboreal positional behaviors soliciting abducted glenohumeral joints in early Pliocene taxa, we propose that the StW 573 pectoral girdle is a reasonable model for hypothesizing pectoral girdle configuration of the crown hominin last common ancestor.

Mesenchymal stem cells and three-dimensional-osteoconductive scaffold regenerate calvarial bone in critical size defects in swine.

Craniofacial bones protect vital organs, perform important physiological functions, and shape facial identity. Critical-size defects (CSDs) in calvarial bones, which will not heal spontaneously, are caused by trauma, congenital defects, or tumor resections. They pose a great challenge for patients and physicians, and significantly compromise quality of life. Currently, calvarial CSDs are treated either by allogenic or autologous grafts, metal or other synthetic plates that are associated with considerable complications. While previous studies have explored tissue regeneration for calvarial defects, most have been done in small animal models with limited translational value. Here we define a swine calvarial CSD model and show a novel approach to regenerate high-quality bone in these defects by combining mesenchymal stem cells (MSCs) with a three-dimensional (3D)-printed osteoconductive HA/TCP scaffold. Specifically, we have compared the performance of dental pulp neural crest MSCs (DPNCCs) to bone marrow aspirate (BMA) combined with a 3D-printed HA/TCP scaffold to regenerate bone in a calvarial CSD (>7.0 cm2 ). Both DPNCCs and BMA loaded onto the 3D-printed osteoconductive scaffold support the regeneration of calvarial bone with density, compression strength, and trabecular structures similar to native bone. Our study demonstrates a novel application of an original scaffold design combined with DPNCCs or BMA to support regeneration of high-quality bone in a newly defined and clinically relevant swine calvarial CSD model. This discovery may have important impact on bone regeneration beyond the craniofacial region and will ultimately benefit patients who suffer from debilitating CSDs.

Pulsed electromagnetic field (PEMF) transiently stimulates the rate of mineralization in a 3-dimensional ring culture model of osteogenesis.

Pulsed Electromagnetic Field (PEMF) has shown efficacy in bone repair and yet the optimum characteristics of this modality and its molecular mechanism remain unclear. To determine the effects of timing of PEMF treatment, we present a novel three-dimensional culture model of osteogenesis that demonstrates strong de novo generation of collagen and mineral matrix and exhibits stimulation by PEMF in multiple stages over 62 days of culture. Mouse postnatal day 2 calvarial pre-osteoblasts were cast within and around Teflon rings by polymerization of fibrinogen and cultured suspended without contact with tissue culture plastic. Ring constructs were exposed to PEMF for 4h/day for the entire culture (Daily), or just during Day1-Day10, Day11-Day 27, or Day28-Day63 and cultured without PEMF for the preceding or remaining days, and compared to no-PEMF controls. PEMF was conducted as HF Physio, 40.85 kHz frequency with a 67 ms burst period and an amplitude of 1.19 mT. Osteogenesis was kinetically monitored by repeated fluorescence measurements of continuously present Alizarin Red S (ARS) and periodically confirmed by micro-CT. PEMF treatment induced early-onset and statistically significant transient stimulation (~4-fold) of the mineralization rate when PEMF was applied Daily, or during D1-D10 and D11-D27. Stimulation was apparent but not significant between D28-D63 by ARS but was significant at D63 by micro-CT. PEMF also shifted the micro-CT density profiles to higher densities in each PEMF treatment group. Ring culture generated tissue with a mineral:matrix ratio of 2.0 by thermogravimetric analysis (80% of the calvaria control), and the deposited crystal structure was 50% hydroxyapatite by X-ray diffraction (63% of the calvaria and femur controls), independent of PEMF. These results were consistent with backscatter, secondary electron, and elemental analysis by scanning electron microscopy. Thus, in a defined, strong osteogenic environment, PEMF applied at different times was capable of further stimulation of osteogenesis with the potential to enhance bone repair.

Combinations of trabecular and cortical bone properties distinguish various loading modalities between athletes and controls.

OBJECTIVES: Variation in trabecular and cortical bone properties is often used to infer habitual behavior in the past. However, the structures of both types of bone are rarely considered together and may even contradict each other in functional interpretations. We examine trabecular and cortical bone properties in various athletes and sedentary controls to clarify the associations between combinations of cortical and trabecular bone properties and various loading modalities. MATERIALS AND METHODS: We compare trabecular and cortical bone properties using peripheral quantitative computed tomography scans of the tibia between groups of 83 male athletes (running, hockey, swimming, cricket) and sedentary controls using Bayesian multilevel models. We quantify midshaft cortical bone rigidity and area (J, CA), midshaft shape index (Imax/Imin), and mean trabecular bone mineral density (BMD) in the distal tibia. RESULTS: All groups show unique combinations of biomechanical properties. Cortical bone rigidity is high in sports that involve impact loading (cricket, running, hockey) and low in nonimpact loaded swimmers and controls. Runners have more anteroposteriorly elliptical midshafts compared to other groups. Interestingly, all athletes have greater trabecular BMD compared to controls, but do not differ credibly among each other. DISCUSSION: Results suggest that cortical midshaft hypertrophy is associated with impact loading while trabecular BMD is positively associated with both impact and nonimpact loading. Midshaft shape is associated with directionality of loading. Individuals from the different categories overlap substantially, but group means differ credibly, suggesting that nuanced group-level inferences of habitual behavior are possible when combinations of trabecular and cortical bone are analyzed.

Automated resolution independent method for comparing in vivo and dry trabecular bone.

OBJECTIVES: Variation in human trabecular bone morphology can be linked to habitual behavior, but it is difficult to investigate in vivo due to the radiation required at high resolution. Consequently, functional interpretations of trabecular morphology remain inferential. Here we introduce a method to link low- and high-resolution CT data from dry and fresh bone, enabling bone functional adaptation to be studied in vivo and results compared to the fossil and archaeological record. MATERIALS AND METHODS: We examine 51 human dry bone distal tibiae from Nile Valley and UK and two pig tibiae containing soft tissues. We compare low-resolution peripheral quantitative computed tomography (pQCT) parameters and high-resolution micro CT (µCT) in homologous single slices at 4% bone length and compare results to our novel Bone Ratio Predictor (BRP) method. RESULTS: Regression slopes between linear attenuation coefficients of low-resolution pQCT images and bone area/total area (BA/TA) of high-resolution µCT scans differ substantially between geographical subsamples, presumably due to diagenesis. BRP accurately predicts BA/TA (R2 = .97) and eliminates the geographic clustering. BRP accurately estimates BA/TA in pigs containing soft tissues (R2 = 0.98) without requiring knowledge of true density or phantom calibration of the scans. DISCUSSION: BRP allows automated comparison of image data from different image modalities (pQCT, µCT) using different energy settings, in archeological bone and wet specimens. The method enables low-resolution data generated in vivo to be compared with the fossil and archaeological record. Such experimental approaches would substantially improve behavioral inferences based on trabecular bone microstructure.

The upper limb skeleton and behavioral lateralization of modern humans from Zhaoguo Cave, southwestern China.

OBJECTIVES: Aims of the study are to initially describe and comparatively evaluate the morphology of the new Zhaoguo M1 upper limb remains, and contextualize upper limb functional adaptations among those of other worldwide Upper Paleolithic (UP) humans to make inferences about subsistence-related activity patterns in southwestern China at the Pleistocene-Holocene boundary. MATERIALS AND METHODS: The preserved Zhaoguo M1 skeletal remains include paired humeri, ulnae, and radii, among others. These specimens were scanned using micro-computed tomography to evaluate internal structural properties, while external osteometric dimensions of the Zhaoguo M1 upper limb elements also were acquired. Both sets of measurements were compared to published data on Neandertals, and Middle and Upper Paleolithic modern humans. RESULTS: The upper limb elements of Zhaoguo M1 display a suite of characteristics that generally resemble those of other contemporary Late UP (LUP) modern humans, while robusticity indices generally fall within the upper range of LUP variation. The Zhaoguo M1 upper limb elements display fewer traits resembling those of late archaic humans. The Zhaoguo M1 individual exhibits diaphyseal asymmetry in several upper limb elements suggesting left hand dominance. When evaluating the full range of magnitudes of humeral bilateral asymmetry in the comparative sample, Zhaoguo M1 falls at the lower end overall, but yet is relatively higher than contemporary LUP modern humans specifically from East Eurasia. DISCUSSION: The Zhaoguo M1 individual suggests typical LUP modern human upper limb morphology persisted in southwest China until the end of the last glacial period. Upper limb bone asymmetry of Zhaoguo M1 also indicates that behavioral activities attributed to a hunter-gatherer tradition apparently extended through the Pleistocene-Holocene transition in this region.

Strength properties of extant hominoid hallucal and pollical metapodials.

Functional comparisons of cortical bone strength properties between hominoid hallucal and pollical metapodials (Mt1 and Mc1, respectively) are lacking. Determining which of these two elements is stronger, and by how much, could be informative because the hallux and pollex are used differently both within and among extant hominoids during locomotion and manipulation (i.e., functional differentiation between autopod pairs). Here, we compare Mt1 and Mc1 midshaft cortical area, polar section modulus, and polar second moment of area, calculated from high-resolution computed tomography images in humans (n = 21), chimpanzees (n = 47), gorillas (n = 24), orangutans (n = 20), siamangs (n = 8), and gibbons (n = 21). Intraindividual comparisons between bones within species were made using paired t-tests. Log10-transformed Mt1:Mc1 ratios were created to assess relative strength asymmetry between bones, and interspecific comparisons of these proportions were made using analyses of variance. Absolute strength differences between the Mt1 and Mc1 for all variables were significantly larger in the Mt1 for all species (p < 0.05). Significant differences across species in Mt1:Mc1 proportions were also found, thereby demonstrating that strength asymmetry between bones differs among taxa (p < 0.05); asymmetry was lowest in orangutans, intermediate in gorillas, and greatest in humans, chimpanzees, siamangs, and gibbons. These findings support the hypothesis that the Mt1 is better adapted structurally than the Mc1 for bearing mechanical loads during weight support of locomotion in all extant hominoids and that pedal hallucal grasping likely engenders higher loads than manual pollical grasping in nonhuman hominoids. Thus, functional differentiation in autopod use within and among hominoids is reflected in hallucal and pollical metapodial strength properties.

Morphometric analysis of the hominin talus: Evolutionary and functional implications.

The adoption of bipedalism is a key benchmark in human evolution that has impacted talar morphology. Here, we investigate talar morphological variability in extinct and extant hominins using a 3D geometric morphometric approach. The evolutionary timing and appearance of modern human-like features and their contributions to bipedal locomotion were evaluated on the talus as a whole, each articular facet separately, and multiple combinations of facets. Distinctive suites of features are consistently present in all fossil hominins, despite the presence of substantial interspecific variation, suggesting a potential connection of these suites to bipedal gait. A modern human-like condition evolved in navicular and lateral malleolar facets early in the hominin lineage compared with other facets, which demonstrate more complex morphological variation within Homininae. Interestingly, navicular facet morphology of Australopithecus afarensis is derived in the direction of Homo, whereas more recent hominin species such as Australopithecus africanus and Australopithecus sediba retain more primitive states in this facet. Combining the navicular facet with the trochlea and the posterior calcaneal facet as a functional suite, however, distinguishes Australopithecus from Homo in that the medial longitudinal arch had not fully developed in the former. Our results suggest that a more everted foot and stiffer medial midtarsal region are adaptations that coincide with the emergence of bipedalism, whereas a high medial longitudinal arch emerges later in time, within Homo. This study provides novel insights into the emergence of talar morphological traits linked to bipedalism and its transition from a facultative to an obligate condition.

The atlas of StW 573 and the late emergence of human-like head mobility and brain metabolism.

Functional morphology of the atlas reflects multiple aspects of an organism's biology. More specifically, its shape indicates patterns of head mobility, while the size of its vascular foramina reflects blood flow to the brain. Anatomy and function of the early hominin atlas, and thus, its evolutionary history, are poorly documented because of a paucity of fossilized material. Meticulous excavation, cleaning and high-resolution micro-CT scanning of the StW 573 ('Little Foot') skull has revealed the most complete early hominin atlas yet found, having been cemented by breccia in its displaced and flipped over position on the cranial base anterolateral to the foramen magnum. Description and landmark-free morphometric analyses of the StW 573 atlas, along with other less complete hominin atlases from Sterkfontein (StW 679) and Hadar (AL 333-83), confirm the presence of an arboreal component in the positional repertoire of Australopithecus. Finally, assessment of the cross-sectional areas of the transverse foramina of the atlas and the left carotid canal in StW 573 further suggests there may have been lower metabolic costs for cerebral tissues in this hominin than have been attributed to extant humans and may support the idea that blood perfusion of these tissues increased over the course of hominin evolution.

A Pre-clinical Animal Model of Secondary Head and Neck Lymphedema.

Head and neck lymphedema (HNL) is a disfiguring disease affecting over 90% of patients treated for head and neck cancer. Animal models of lymphedema are used to test pharmacologic and microsurgical therapies; however, no animal model for HNL is described in the literature to date. In this study we describe the first reproducible rat model for HNL. Animals were subjected to two surgical protocols: (1) lymphadenectomy plus irradiation; and (2) sham surgery and no irradiation. Head and neck expansion was measured on post-operative days 15, 30 and 60. Magnetic resonance imaging (MRI) was acquired at the same time points. Lymphatic drainage was measured at day 60 via indocyanine green (ICG) lymphography, after which animals were sacrificed for histological analysis. Postsurgical lymphedema was observed 100% of the time. Compared to sham-operated animals, lymphadenectomy animals experienced significantly more head and neck swelling at all timepoints (P < 0.01). Lymphadenectomy animals had significantly slower lymphatic drainage for 6 days post-ICG injection (P < 0.05). Histological analysis of lymphadenectomy animals revealed 83% greater subcutis thickness (P = 0.008), 22% greater collagen deposition (P = 0.001), 110% greater TGFß1+ cell density (P = 0.04), 1.7-fold increase in TGFß1 mRNA expression (P = 0.03), and 114% greater T-cell infiltration (P = 0.005) compared to sham-operated animals. In conclusion, animals subjected to complete lymph node dissection and irradiation developed changes consistent with human clinical postsurgical HNL. This was evidenced by significant increase in all head and neck measurements, slower lymphatic drainage, subcutaneous tissue expansion, increased fibrosis, and increased inflammation compared to sham-operated animals.

The long limb bones of the StW 573 Australopithecus skeleton from Sterkfontein Member 2: Descriptions and proportions.

Due to its completeness, the A.L. 288-1 ('Lucy') skeleton has long served as the archetypal bipedal Australopithecus. However, there remains considerable debate about its limb proportions. There are three competing, but not necessarily mutually exclusive, explanations for the high humerofemoral index of A.L. 288-1: (1) a retention of proportions from an Ardipithecus-like chimp/human last common ancestor (CLCA); (2) indication of some degree of climbing ability; (3) allometry. Recent discoveries of other partial skeletons of Australopithecus, such as those of Australopithecus sediba (MH1 and MH2) and Australopithecus afarensis (KSD-VP-1/1 and DIK-1/1), have provided new opportunities to test hypotheses of early hominin body size and limb proportions. Yet, no early hominin is as complete (>90%), as is the ∼3.67 Ma 'Little Foot' (StW 573) skeleton from Sterkfontein Member 2. Here, we provide the first descriptions of its upper and lower long limb bones, as well as a comparative context of its limb proportions. We found that StW 573 possesses absolutely longer limb lengths than A.L. 288-1, but both skeletons show similar limb proportions. This finding seems to argue against a purely allometric explanation for A.L. 288-1 limb proportions. In fact, our multivariate allometric analysis suggests that limb lengths of Australopithecus, as represented by StW 573 and A.L. 288-1, exhibit a significantly different (p < 0.001) allometric pattern than that which typifies modern humans and African apes. Like some previous analyses, our results also suggest that hominin limb evolution occurred in two stages with: first, a modest increase in lower limb length and a concurrent shortening of the antebrachium between Ardipithecus and Australopithecus, followed by a considerable lengthening of the lower limb along with a decrease of both upper limb elements occurring between Australopithecus and Homo sapiens.

A multiscale stratigraphic investigation of the context of StW 573 'Little Foot' and Member 2, Sterkfontein Caves, South Africa.

The Sterkfontein Caves is currently the world's richest Australopithecus-bearing site. Included in Sterkfontein's hominin assemblage is StW 573 ('Little Foot'), a near-complete Australopithecus skeleton discovered in Member 2 in the Silberberg Grotto. Because of its importance to the fossil hominin record, the geological age of StW 573 has been the subject of significant debate. Three main hypotheses have been proposed regarding the formation and age of Member 2 and by association StW 573. The first proposes that Member 2 (as originally defined in the type section in the Silberberg Grotto) started to accumulate at around 2.58 Ma and that the unit is contained within the Silberberg Grotto. The second proposes that Member 2 started forming before 3.67 ± 0.16 Ma and that the deposit extends into the Milner Hall and close to the base of the cave system. The third proposes a 'two-stage burial scenario', in which some sediments and StW 573 represent a secondary and mixed-age accumulation reworked from a higher cave. The stratigraphic and sedimentological implications of these hypotheses are tested here through the application of a multiscale investigation of Member 2, with reference to the taphonomy of the StW 573 skeleton. The complete infilling sequence of Member 2 is described across all exposures of the deposit in the Silberberg Grotto and into the Milner Hall. Sediments are generally stratified and conformably deposited in a sequence of silty sands eroded from well-developed lateritic soils on the landscape surface. Voids, clasts and bioclasts are organized consistently across and through Member 2 conforming with the underlying deposit geometry, indicating gradual deposit accretion with no distinct collapse facies evident and only localized intra-unit postdepositional modification. The stratigraphy and sedimentology of Member 2 support a simple single-stage accumulation process of Member 2 and a primary association between the sediments of Member 2 and the StW 573 'Little Foot' skeleton.

The bony labyrinth of StW 573 ("Little Foot"): Implications for early hominin evolution and paleobiology.

Because of its exceptional degree of preservation and its geological age of ∼3.67 Ma, StW 573 makes an invaluable contribution to our understanding of early hominin evolution and paleobiology. The morphology of the bony labyrinth has the potential to provide information about extinct primate taxonomic diversity, phylogenetic relationships and locomotor behaviour. In this context, we virtually reconstruct and comparatively assess the bony labyrinth morphology in StW 573. As comparative material, we investigate 17 southern African hominin specimens from Sterkfontein, Swartkrans and Makapansgat (plus published data from two specimens from Kromdraai B), attributed to Australopithecus, early Homo or Paranthropus, as well as 10 extant human and 10 extant chimpanzee specimens. We apply a landmark-based geometric morphometric method for quantitatively assessing labyrinthine morphology. Morphology of the inner ear in StW 573 most closely resembles that of another Australopithecus individual from Sterkfontein, StW 578, recovered from the Jacovec Cavern. Within the limits of our sample, we observe a certain degree of morphological variation in the Australopithecus assemblage of Sterkfontein Member 4. Cochlear morphology in StW 573 is similar to that of other Australopithecus as well as to Paranthropus specimens included in this study, but it is substantially different from early Homo. Interestingly, the configuration of semicircular canals in Paranthropus specimens from Swartkrans differs from other fossil hominins, including StW 573. Given the role of the cochlea in the sensory-driven interactions with the surrounding environment, our results offer new perspectives for interpreting early hominin behaviour and ecology. Finally, our study provides additional evidence for discussing the phylogenetic polarity of labyrinthine traits in southern African hominins.