Cochlear shape distinguishes southern African early hominin taxa with unique auditory ecologies.

Insights into potential differences among the bony labyrinths of Plio-Pleistocene hominins may inform their evolutionary histories and sensory ecologies. We use four recently-discovered bony labyrinths from the site of Kromdraai to significantly expand the sample for Paranthropus robustus. Diffeomorphometry, which provides detailed information about cochlear shape, reveals size-independent differences in cochlear shape between P. robustus and Australopithecus africanus that exceed those among modern humans and the African apes. The cochlea of P. robustus is distinctive and relatively invariant, whereas cochlear shape in A. africanus is more variable, resembles that of early Homo, and shows a degree of morphological polymorphism comparable to that evinced by modern species. The curvature of the P. robustus cochlea is uniquely derived and is consistent with enhanced sensitivity to low-frequency sounds. Combined with evidence for selection, our findings suggest that sound perception shaped distinct ecological adaptations among southern African early hominins.

Direct detection and characterization of foot-and-mouth disease virus in East Africa using a field-ready real-time PCR platform.

Effective control and monitoring of foot-and-mouth disease (FMD) relies upon rapid and accurate disease confirmation. Currently, clinical samples are usually tested in reference laboratories using standardized assays recommended by The World Organisation for Animal Health (OIE). However, the requirements for prompt and serotype-specific diagnosis during FMD outbreaks, and the need to establish robust laboratory testing capacity in FMD-endemic countries have motivated the development of simple diagnostic platforms to support local decision-making. Using a portable thermocycler, the T-COR™ 8, this study describes the laboratory and field evaluation of a commercially available, lyophilized pan-serotype-specific real-time RT-PCR (rRT-PCR) assay and a newly available FMD virus (FMDV) typing assay (East Africa-specific for serotypes: O, A, Southern African Territories [SAT] 1 and 2). Analytical sensitivity, diagnostic sensitivity and specificity of the pan-serotype-specific lyophilized assay were comparable to that of an OIE-recommended laboratory-based rRT-PCR (determined using a panel of 57 FMDV-positive samples and six non-FMDV vesicular disease samples for differential diagnosis). The FMDV-typing assay was able to correctly identify the serotype of 33/36 FMDV-positive samples (no cross-reactivity between serotypes was evident). Furthermore, the assays were able to accurately detect and type FMDV RNA in multiple sample types, including epithelial tissue suspensions, serum, oesophageal-pharyngeal (OP) fluid and oral swabs, both with and without the use of nucleic acid extraction. When deployed in laboratory and field settings in Tanzania, Kenya and Ethiopia, both assays reliably detected and serotyped FMDV RNA in samples (n = 144) collected from pre-clinical, clinical and clinically recovered cattle. These data support the use of field-ready rRT-PCR platforms in endemic settings for simple, highly sensitive and rapid detection and/or characterization of FMDV.

Landscape scale heterogeneity in the East Turkana ecosystem during the Okote Member (1.56-1.38 Ma).

Placing the biological adaptations of Pleistocene hominins within a well-resolved ecological framework has been a longstanding goal of paleoanthropology. This effort, however, has been challenging due to the discontinuous nature of paleoecological data spanning many important periods in hominin evolution. Sediments from the Upper Burgi (1.98-1.87 Ma), KBS (1.87-1.56 Ma) and Okote (1.56-1.38 Ma) members of the Koobi Fora Formation at East Turkana in northern Kenya document an important time interval in the evolutionary history of the hominin genera Homo and Paranthropus. Although much attention has been paid to Upper Burgi and KBS member deposits, far less is known regarding the East Turkana paleoecosystem during Okote Member times. This study pairs spatially-resolved faunal abundance data with stable isotope geochemistry from mammalian enamel to investigate landscape-scale ecosystem variability during Okote Member times. We find that during this period 1) taxa within the East Turkana large mammal community were distributed heterogeneously across space, 2) the abundance of C3 and C4 vegetation varied between East Turkana subregions, and 3) the Karari subregion, an area with abundant evidence of hominin stone tool manufacture, had significantly more C3 vegetation than regions closer to the central axis of the Turkana Basin (i.e., Ileret and Koobi Fora). These findings indicate that the East Turkana paleoecosystem during the Okote Member was highly variable across space and provided a complex adaptive landscape for Pleistocene hominins.

Characterization of Foot-and-Mouth Disease Viruses Collected in Nigeria Between 2007 and 2014: Evidence for Epidemiological Links Between West and East Africa.

This study describes the molecular characterization of 47 foot-and-mouth disease (FMD) viruses recovered from field outbreaks in Nigeria between 2007 and 2014. Antigen ELISA of viral isolates was used to identify FMD virus serotypes O, A and SAT 2. Phylogenetic analyses of VP1 nucleotide sequences provide evidence for the presence of multiple sublineages of serotype SAT 2, and O/EAST AFRICA 3 (EA-3) and O/WEST AFRICA topotypes in the country. In contrast, for serotype A, a single monophyletic cluster of viruses has persisted within Nigeria (2009-2013). These results demonstrate the close genetic relatedness of viruses in Nigeria to those from other African countries, including the first formal characterization of serotype O/EA-3 viruses in Nigeria. The introductions and persistence of certain viral lineages in Nigeria may reflect transmission patterns via nomadic pastoralism and animal trade. Continuous monitoring of field outbreaks is necessary to dissect the complexity of FMD epidemiology in sub-Saharan Africa.

CD117 and CD43 are useful adjuncts in the distinction of adenoid cystic carcinoma from adenoid basal cell carcinoma.

Distinction of cutaneous adenoid cystic carcinoma (ACC) from adenoid basal cell carcinoma (BCC) is an occasional diagnostic dilemma in dermatopathology.We examined the immunohistochemical staining patterns with CD117 and CD43 in ACCs and BCCs, including BCCs with an adenoid growth pattern, to determine whether a combination of these markers can assist in the differential diagnosis.Fifteen cases each of ACC and BCC, including seven BCCs with a partial or entirely adenoid growth pattern were immunohistochemically stained for CD117 and CD43. The stains were interpreted semi-quantitatively.Staining for CD43 and CD117 was significantly more common in ACC than in BCC. Forty percent of ACCs showed staining for CD43, while no cases of BCC were positive. CD117 was positive in all cases of ACC, with 93% showing moderate or strong staining. BCC were less frequently positive, with only 20% of cases showing labelling of weak or moderate intensity.Immunohistochemical positivity for CD117 and CD43 are likely to be helpful adjuncts in the separation of cutaneous ACC from adenoid BCC.

Notch-induced transcription factors are predictive of survival and 5-fluorouracil response in colorectal cancer patients.

BACKGROUND: The purpose of this study was to evaluate the expression of Notch-induced transcription factors (NTFs) HEY1, HES1 and SOX9 in colorectal cancer (CRC) patients to determine their clinicopathologic and prognostic significance. METHODS: Levels of HEY1, HES1 and SOX9 protein were measured by immunohistochemistry in a nonmalignant and malignant tissue microarray of 441 CRC patients, and the findings correlated with pathologic, molecular and clinical variables. RESULTS: The NTFs HEY1, HES1 and SOX9 were overexpressed in tumours relative to colonic mucosa (OR=3.44, P<0.0001; OR=7.40, P<0.0001; OR=4.08 P<0.0001, respectively). HEY1 overexpression was a negative prognostic factor for all CRC patients (HR=1.29, P=0.023) and strongly correlated with perineural and vascular invasion and lymph node (LN) metastasis. In 5-fluorouracil (5-FU)-treated patients, the tumour overexpression of SOX9 correlated with markedly poorer survival (HR=8.72, P=0.034), but had no predictive effect in untreated patients (HR=0.70, P=0.29). When HEY1, HES1 and SOX9 expression were combined to predict survival with chemotherapy, in treated patients there was an additive increase in the risk of death with each NTF overexpressed (HR=2.09, P=0.01), but no prognostic import in the untreated patient group (HR=0.74, P=0.19). CONCLUSION: The present study is the first to discover that HEY1 overexpression correlates with poorer outcome in CRC, and NTF expression is predictive of CRC patient survival with 5-FU chemotherapy. If confirmed in future studies, testing of NTF expression has the potential to enter routine pathological practice for the selection of patients to undergo chemotherapy alone or in combination with Notch inhibitors.

Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer.

BACKGROUND: AT-101 (A), a small molecule oral inhibitor of the Bcl-2 family, has activity alone and in combination with docetaxel (Taxotere) and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC). A randomized, double-blind, placebo-controlled phase II trial compared DP combined with either AT-101 (A) or placebo in chemonaive mCRPC. PATIENTS AND METHODS: Men with progressive mCRPC despite androgen deprivation were eligible and randomized 1:1. Patients received docetaxel (75 mg/m2 day 1) and prednisone 5 mg orally twice daily every 21 days with either AT-101 (40 mg) or placebo twice daily orally on days 1-3. The primary end point was overall survival (OS). RESULTS: Two hundred and twenty-one patients were randomly assigned. Median OS for AT-101 plus docetaxel-prednisone (ADP) and placebo-DP was 18.1 versus 17.8 months [hazard ratio (HR) 1.07, 95% confidence interval 0.72-1.55, P=0.63]. Secondary end points were also not statistically different. Grade 3/4 toxic effects for ADP versus placebo-DP were cardiac events (5% versus 2%), lymphopenia (23% versus 16%), neutropenia (47% versus 40%), ileus (2% versus 0%) and pulmonary embolism (6% versus 2%). In a subgroup of high-risk mCRPC (n=34), outcomes appeared to favor ADP (median OS 19 versus 14 months). CONCLUSIONS: AT-101 was tolerable but did not extend OS when combined with DP in mCRPC; a potential benefit was observed in high-risk patients.

On the origin, homologies and evolution of primate facial muscles, with a particular focus on hominoids and a suggested unifying nomenclature for the facial muscles of the Mammalia.

The mammalian facial muscles are a subgroup of hyoid muscles (i.e. muscles innervated by cranial nerve VII). They are usually attached to freely movable skin and are responsible for facial expressions. In this study we provide an account of the origin, homologies and evolution of the primate facial muscles, based on dissections of various primate and non-primate taxa and a review of the literature. We provide data not previously reported, including photographs showing in detail the facial muscles of primates such as gibbons and orangutans. We show that the facial muscles usually present in strepsirhines are basically the same muscles that are present in non-primate mammals such as tree-shrews. The exceptions are that strepsirhines often have a muscle that is usually not differentiated in tree-shrews, the depressor supercilii, and lack two muscles that are usually differentiated in these mammals, the zygomatico-orbicularis and sphincter colli superficialis. Monkeys such as macaques usually lack two muscles that are often present in strepsirhines, the sphincter colli profundus and mandibulo-auricularis, but have some muscles that are usually absent as distinct structures in non-anthropoid primates, e.g. the levator labii superioris alaeque nasi, levator labii superioris, nasalis, depressor septi nasi, depressor anguli oris and depressor labii inferioris. In turn, macaques typically lack a risorius, auricularis anterior and temporoparietalis, which are found in hominoids such as humans, but have muscles that are usually not differentiated in members of some hominoid taxa, e.g. the platysma cervicale (usually not differentiated in orangutans, panins and humans) and auricularis posterior (usually not differentiated in orangutans). Based on our observations, comparisons and review of the literature, we propose a unifying, coherent nomenclature for the facial muscles of the Mammalia as a whole and provide a list of more than 300 synonyms that have been used in the literature to designate the facial muscles of primates and other mammals. A main advantage of this nomenclature is that it combines, and thus creates a bridge between, those names used by human anatomists and the names often employed in the literature dealing with non-human primates and non-primate mammals.

From fish to modern humans--comparative anatomy, homologies and evolution of the pectoral and forelimb musculature.

In a recent study Diogo & Abdala [(2007) J Morphol 268, 504-517] reported the results of the first part of a research project on the comparative anatomy, homologies and evolution of the pectoral muscles of osteichthyans (bony fish and tetrapods). That report mainly focused on actinopterygian fish but also compared these fish with certain non-mammalian sarcopterygians. This study, which reports the second part of the research project, focuses mainly on sarcopterygians and particularly on how the pectoral and forelimb muscles have evolved during the transitions from sarcopterygian fish and non-mammalian tetrapods to monotreme and therian mammals and humans. The data obtained by our own dissections of all the pectoral and forelimb muscles of representative members of groups as diverse as sarcopterygian fish, amphibians, reptiles, monotremes and therian mammals such as rodents, tree-shrews, colugos and primates, including humans, are compared with the information available in the literature. Our observations and comparisons clearly stress that, with regard to the number of pectoral and forelimb muscles, the most striking transition within sarcopterygian evolutionary history was that leading to the origin of tetrapods. Whereas extant sarcopterygian fish have an abductor and adductor of the fin and a largely undifferentiated hypaxial and epaxial musculature, extant salamanders such as Ambystoma have more than 40 pectoral and forelimb muscles. There is no clear increase in the number of pectoral and forelimb muscles within the evolutionary transition that led to the origin of mammals and surely not to that leading to the origin of primates and humans.

From fish to modern humans--comparative anatomy, homologies and evolution of the head and neck musculature.

In a recent paper Diogo (2008) reported the results of the first part of an investigation of the comparative anatomy, homologies and evolution of the head and neck muscles of osteichthyans (bony fish + tetrapods). That report mainly focused on actinopterygian fish, but also compared these fish with certain non-mammalian sarcopterygians. The present paper focuses mainly on sarcopterygians, and particularly on how the head and neck muscles have evolved during the transitions from sarcopterygian fish and non-mammalian tetrapods to monotreme and therian mammals, including modern humans. The data obtained from our dissections of the head and neck muscles of representative members of sarcopterygian fish, amphibians, reptiles, monotremes and therian mammals, such as rodents, tree-shrews, colugos and primates, including modern humans, are compared with the information available in the literature. Our observations and comparisons indicate that the number of mandibular and true branchial muscles (sensu this work) present in modern humans is smaller than that found in mammals such as tree-shrews, rats and monotremes, as well as in reptiles such as lizards. Regarding the pharyngeal musculature, there is an increase in the number of muscles at the time of the evolutionary transition leading to therian mammals, but there was no significant increase during the transition leading to the emergence of higher primates and modern humans. The number of hypobranchial muscles is relatively constant within the therian mammals we examined, although in this case modern humans have more muscles than other mammals. The number of laryngeal and facial muscles in modern humans is greater than that found in most other therian taxa. Interestingly, modern humans possess peculiar laryngeal and facial muscles that are not present in the majority of the other mammalian taxa; this seems to corroborate the crucial role played by vocal communication and by facial expressions in primate and especially in human evolution. It is hoped that by compiling, in one paper, data about the head and neck muscles of a wide range of sarcopterygians, the present work could be useful to comparative anatomists, evolutionary biologists and functional morphologists and to researchers working in other fields such as developmental biology, genetics and/or evolutionary developmental biology.

Early hominid biogeography.

We examined the biogeographic patterns implied by early hominid phylogenies and compared them to the known dispersal patterns of Plio-Pleistocene African mammals. All recent published phylogenies require between four and seven hominid dispersal events between southern Africa, eastern Africa, and the Malawi Rift, a greater number of dispersals than has previously been supposed. Most hominid species dispersed at the same time and in the same direction as other African mammals. However, depending on the ages of critical hominid specimens, many phylogenies identify at least one hominid species that dispersed in the direction opposite that of contemporaneous mammals. This suggests that those hominids may have possessed adaptations that allowed them to depart from continental patterns of mammalian dispersal.

Evolution of the gibbon subgenera inferred from cytochrome b DNA sequence data.

DNA sequences for the mitochondrial cytochrome b gene from the four extant gibbon subgenera are described. The data confirm that the gibbon subgenera evolved from a common hylobatid ancestor and suggest that they diverged from each other after the divergence of the extant African great ape species. The cytochrome b gene does not resolve the evolutionary relationships between the gibbon subgenera themselves.

Cranial variables as predictors of hominine body mass.

Body mass is a key variable in investigating the evolutionary biology of the hominines (Australopithecus, Paranthropus, and Homo). It is not only closely related to life-history parameters but also provides a necessary baseline for studies of encephalization or megadonty. Body mass estimates are normally based on the postcranial skeleton. However, the majority of hominid fossils are cranio-dental remains that are unassociated with post-cranial material. Only rarely can postcranial material be linked with cranio-dentally defined hominid taxa. This study responds to this problem by evaluating body mass estimates based on 15 cranial variables to determine whether they compare in reliability with estimates determined from postcranial variables. Results establish that some cranial variables, and particularly orbital area, orbital height, and biporionic breadth, are nearly as good mass predictors for hominoids as are some of the best postcranial predictors. For the hominines in particular, orbital height is the cranial variable which produces body mass estimates that are most in line with postcranially generated estimates. Both orbital area and biporionic breadth scale differently in the hominines than they do in the other hominoids. This difference in scaling results in unusually large estimates of body mass based on these variables for the larger-sized hominines, although the three cranial variables produce equivalent predicted masses for the smaller-bodied hominines.

Further analysis of mandibular molar crown and cusp areas in Pliocene and early Pleistocene hominids.

Crown and cusp areas of mandibular molars were measured and analyzed on a sample of 249 specimens attributed to Australopithecus afarensis, A. africanus, A. (Paranthropus) robustus, A. (P.) boisei, and early Homo. In addition to intertaxon comparisons, we compared data that had been collected independently by two of the authors using methods that differ slightly in technique of measurement. Interobserver differences were evaluated by the t-test of paired comparisons, method error statistic, percent differences, and principal component analysis. Results suggest that between-technique error of measurement of overall crown area is small. Error estimates for individual cusp area measurements were of larger relative magnitude. However, these were not sufficient to detract from the conclusions derived from comparative analyses. Our results are in general agreement with previous assessments of early hominid dental size. Crown areas of A. africanus, however, exhibit a mosaic pattern, with M1 similar in size to that of A. afarensis and early Homo, and M2 and M3 similar in size to that of A. robustus. Intertaxon comparisons of relative cusp area were undertaken by univariate statistics and principal component analysis. These analyses revealed that while A. (P.) robustus and A. (P.) boisei both possess mandibular molars with cusp proportions significantly different from the 'non-robust' taxa, these differences are substantially greater in A. (P.) boisei.

Comparison of medical-grade ultrahigh molecular weight polyethylene microstructure by atomic force microscopy and transmission electron microscopy.

Atomic force microscopy is used to image the topography of surfaces of bulk medical-grade ultrahigh molecular weight polyethylene (UHMWPE). Comparison with transmission electron microscopy images demonstrates that the AFM can resolve the plate-like stacks of crystalline lamellae characteristic of UHMWPE without aggressive surface treatment. Surface preparation for the AFM must be carried out by cryomicrotomy at extremely low temperatures to prevent smearing of surface features. Chemically-etched surfaces of UHMWPE require substantially less surface preparation for AFM imaging.

Intraspecific variation and sexual dimorphism in cranial and dental variables among higher primates and their bearing on the hominid fossil record.

The extent and nature of dental and cranial sexual dimorphisms in extant hominoids have been investigated using reliably sexed samples of Homo sapiens (n = 75), Pan troglodytes (n = 51), Gorilla gorilla (n = 64) and Pongo pygmaeus (n = 43). Seventy nine measurements (35 dental, 16 mandibular and 28 cranial) formed the basis of the study. The patterns of mean differences and dispersions between the taxa were compared across the anatomical regions and the group structures of the separate sex samples were analysed using multivariate (PCA and CVA) analysis. Within and between group variations were compared across the taxa to investigate whether any variables were consistently effective sex or taxonomic discriminators. The study confirmed that there were differences in degree and pattern of sexual dimorphism between the extant higher primates, but the results did not substantiate the distribution of patterns as suggested by Oxnard et al. (1985); in particular there was no evidence of the dispersion differences noted by those authors. There were sufficient consistencies in the behaviour of variables across the four taxa to suggest that all canine dimensions, postcanine crown buccolingual dimensions and mandibular and cranial breadths are generally good sex discriminators, whereas some incisor dimensions, postcanine crown mesiodistal dimensions and facial heights are more effective at discriminating between the four extant taxa included in this study.

Character phylogeny of the primate forelimb superficial venous system.

The ontogeny and comparative anatomy of the forelimb superficial veins were investigated in humans, non-human primates and other mammals. Adult humans and the orangutan (Pongo) possess two autonomous forelimb veins, one on the lateral (preaxial) margin of the limb, the other on the medial (postaxial) margin. All other adult primates and mammals examined possess a lateral vein alone. In African apes (Pan and Gorilla) and in 24% of human forelimbs the lateral vein is short, being essentially confined to the antebrachial region, whereas in other mammals and in 76% of human limbs the lateral vein runs from the carpus to the clavicular region. In humans the medial vein develops before the lateral vein, whereas in the rabbit and the pig the medial vein is present in early embryos but is subsequently lost. We propose that in humans, and probably also in the orangutan, the possession of a medial vein is a neotenic retention of a primitive tetrapod condition. These animals, which retain their medial vein, are united by losing a late stage in their ontogeny. Other animals subsequently pass through a stage in which the medial vein is lost, but Pongo and Homo retain this vein to adulthood. The loss of an ontogenetic stage can arise independently, and the presence of a medial vein therefore affords only weak evidence for a close phylogenetic relationship between humans and the orangutan. The polymorphic lateral vein of humans may be a character state that is intermediate between the derived (short) lateral vein of the African apes and the primitive long lateral vein of other non-human primates and mammals.

Position and orientation of the foramen magnum in higher primates.

The location of the foramen magnum, with respect to the longitudinal axis of the cranium, and its orientation with respect to the Frankfurt Horizontal, have been studied in a total of 328 modern human and Pan crania. The samples were chosen in order to examine the effect of overall size difference on foramen magnum disposition. Foramen position (expressed as three indices) and inclination are relatively invariant among the modern human samples, but the foramen magnum is consistently, and statistically significantly, more anteriorly located in Pan paniscus than in Pan troglodytes. Sexual dimorphism is virtually non-existent. There is an apparent allometric effect on foramen position, but not on inclination, so that larger crania in the modern human and Pan paniscus samples tend to have more posteriorly situated foramina. The disposition of the foramen is unrelated to cranial base angle or facial prognathism, except that in Pan paniscus its relative anterior location is linked with the more flexed cranial base in that species. These results provide a comparative context for the examination of differences in foramen magnum disposition in fossil hominids. Differences in foramen magnum position and orientation between KNM-ER 1813 and A. africanus are most unlikely to be due to within-taxon variability.