Homo bodoensis and why it matters.

In our original paper, we proposed a new species, Homo bodoensis, to replace the problematical taxa Homo heidelbergensis and Homo rhodesiensis, with the goal of streamlining communication about human evolution in the Chibanian. We received two independent responses. Given their substantial overlap, we provide one combined reply. In this response: (1) we are encouraged that the primary proposal in our paper, to discontinue the use of H. heidelbergensis (as a junior synonym to Homo neanderthalensis) due to its' nomenclatural problems, is acknowledged. (2) we provide additional clarification about the rules governing taxonomic nomenclature as outlined by the International Code of Zoological Nomenclature and join the growing calls for a revision to these rules. (3) we discuss further why H. rhodesiensis should be abandoned, particularly in light of the current sensitivity to using culturally inappropriate names. We conclude that H. bodoensis is a better solution than the proposed alternatives.

Evolution of cranial capacity revisited: A view from the late Middle Pleistocene cranium from Xujiayao, China.

The Late Middle Pleistocene hominin fossils from the Xujiayao site in northern China have been closely studied in light of their morphological variability. However, all previous studies have focused on separated cranial fragments. Here, we report the first reconstruction of a fairly complete posterior cranium, Xujiayao 6 (XJY 6), confidently dated to ∼200-160 ka, which facilitated an assessment of its overall cranial size. XJY 6 was reconstructed from three of the original fragments-the PA1486 (No.7/XJY 6a) occipital bone, PA1490 (No.10/XJY 6b) right parietal bone, and PA1498 (No.17/XJY 15) left temporal bone-which originated from the same young adult individual. The XJY 6 endocranial capacity, estimated by measuring endocranial volume, was estimated using multiple regression formulae derived from ectocranial and endocranial measurements on select samples of Pleistocene hominins and recent modern humans. The results indicate that the larger pooled sample of both Pleistocene and recent modern humans was more robust for the endocranial capacity estimate. Based on the pooled sample using the ectocranial and endocranial measurements, we conservatively estimate the XJY 6 endocranial volume to be ∼1700 cm3 with a 95% confidence interval of 1555-1781 cm3. This is close to Xuchang 1, which dates to 125-105 ka and whose endocranial volume is ∼1800 cm3. Thus, XJY 6 provides the earliest evidence of a brain size that falls in the upper range of Neanderthals and modern Homo sapiens. XJY 6, together with Xuchang 1, Homo floresiensis, Homo luzonensis, and Homo naledi, challenge the general pattern that brain size gradually increases over geological time. This study also finds that hominin brain size expansion occurred at different rates across time and space.

Resolving the "muddle in the middle": The case for Homo bodoensis sp. nov.

Recent developments in the field of palaeoanthropology necessitate the suppression of two hominin taxa and the introduction of a new species of hominins to help resolve the current nebulous state of Middle Pleistocene (Chibanian) hominin taxonomy. In particular, the poorly defined and variably understood hominin taxa Homo heidelbergensis (both sensu stricto and sensu lato) and Homo rhodesiensis need to be abandoned as they fail to reflect the full range of hominin variability in the Middle Pleistocene. Instead, we propose: (1) introduction of a new taxon, Homo bodoensis sp. nov., as an early Middle Pleistocene ancestor of the Homo sapiens lineage, with a pan-African distribution that extends into the eastern Mediterranean (Southeast Europe and the Levant); (2) that many of the fossils from Western Europe (e.g. Sima de los Huesos) currently assigned to H. heidelbergensis s.s. be reassigned to Homo neanderthalensis to reflect the early appearance of Neanderthal derived traits in the Middle Pleistocene in the region; and (3) that the Middle Pleistocene Asian fossils, particularly from China, likely represent a different lineage altogether.

TROAP regulates cell cycle and promotes tumor progression through Wnt/ß-Catenin signaling pathway in glioma cells.

AIMS: Experimental evidence demonstrated a crucial role of TROAP (Trophinin-associated protein) in regulating the cell proliferation of multiple tumors, while TROAP expression and function were largely unknown in glioma. We aimed to investigate the oncogenic role of TROAP and its potential mechanisms in gliomagenesis. METHODS: Four gene expression databases (GEO, TCGA, GTEx and CCLE) were enrolled in our study and used for TROAP expression and survival analysis. TROAP expression was quantified by qRT-PCR, western blot and immunohistochemistry assays in glioma tissues and cell lines. TROAP knockdown and overexpression vector were constructed and transfected into glioma cells. CCK-8, colony formation, transwell, and wound healing assays were used to evaluate cell viability, migration and invasion, flow cytometry to determine cell cycle arrest. Gene set enrichment analysis (GSEA) was conducted to screen the pathway involved in TROAP-high phenotype. The expression of cell cycle and Wnt/ß-Catenin signaling proteins were analyzed by immunofluorescence and western blot. RESULTS: Based on the bioinformatic analysis and a series of functional assays, we found the TROAP was enriched in glioma tissues and cell lines, its overexpression was correlated with the clinicopathologic characteristics and poor prognosis. TROAP knockdown inhibited cell proliferation, migration, invasion, and G1/S cell cycle arrest compared with control group in glioma. Mechanism analysis revealed that TROAP activated Wnt/ß-Catenin pathway and upregulated its downstream targets expression, while silencing ß-Catenin or Axin2 could reverse the tumor-promoting effects caused by TROAP, confirming that TROAP-induced malignant phenotype and tumorigenesis via Wnt/ß-Catenin signaling pathway. CONCLUSION: The present study found that TROAP accelerated the progression of gliomagenesis through Wnt/ß-Catenin pathway, and TROAP might be considered as a novel target for glioma therapy.

Middle Pleistocene human femoral diaphyses from Hualongdong, Anhui Province, China.

OBJECTIVES: The paleontological description and comparative analysis using discrete morphology, morphometrics (linear and geometric) and cross-sectional geometry of three femoral diaphyseal sections from the Middle Pleistocene site of Hualongdong, China. MATERIALS AND METHODS: The material consists of the original Hualongdong femoral fossils and available data on femoral diaphyses from Middle and Late Pleistocene archaic humans and Middle and earlier Upper Paleolithic modern humans. The methods include visual observation, diaphyseal diameters, cross-sectional parameters (transverse areas and second moments of area derived from micro-CT scans), and geometric morphometrics using semilandmark data. RESULTS: The Hualong 11 midshaft section is similar to other Middle and Late Pleistocene archaic humans in being transversely broad and lacking a pilaster despite a prominent linea aspera. It clusters principally with archaic human femora in all measured parameters. The Hualong 15 and 16 subtrochanteric pieces are similar to many Middle Pleistocene and early modern human femora in being transversely broad. In particular, Hualong 15 exhibits a prominent lateral (gluteal) buttress, similar to many Upper Paleolithic femora but also the Lazaret and Krapina archaic ones. In addition, Hualong 15 has a small third trochanter, a common Upper Paleolithic but rare earlier feature. DISCUSSION: The Hualong 11 femoral piece reinforces the general Middle Pleistocene pattern, especially for eastern Eurasia from which archaic human femora are rare. The subtrochanteric proportions of Hualong 15 and 16 reinforce the Early Pleistocene and (generally) Middle Pleistocene pattern of bone distributions, but their subperiosteal contours align them (along with those of the Lazaret and Krapina femora) with Upper Paleolithic ones. It is difficult to account for these proportions from the generally broad pelves of Pleistocene archaic humans.

Archaic human remains from Hualongdong, China, and Middle Pleistocene human continuity and variation.

Middle to Late Pleistocene human evolution in East Asia has remained controversial regarding the extent of morphological continuity through archaic humans and to modern humans. Newly found ∼300,000-y-old human remains from Hualongdong (HLD), China, including a largely complete skull (HLD 6), share East Asian Middle Pleistocene (MPl) human traits of a low vault with a frontal keel (but no parietal sagittal keel or angular torus), a low and wide nasal aperture, a pronounced supraorbital torus (especially medially), a nonlevel nasal floor, and small or absent third molars. It lacks a malar incisure but has a large superior medial pterygoid tubercle. HLD 6 also exhibits a relatively flat superior face, a more vertical mandibular symphysis, a pronounced mental trigone, and simple occlusal morphology, foreshadowing modern human morphology. The HLD human fossils thus variably resemble other later MPl East Asian remains, but add to the overall variation in the sample. Their configurations, with those of other Middle and early Late Pleistocene East Asian remains, support archaic human regional continuity and provide a background to the subsequent archaic-to-modern human transition in the region.

Tannic acid mediated induction of apoptosis in human glioma Hs 683 cells.

Tannic acid (TA), a natural plant compound, is known to induce the death of cancer cells in various types of cancer. The present study was designed with the aim of exploring the effects of tannic acid in vitro on HS 683, a glioma cell line, and to study the mechanism involved in the induction of cytotoxicity and apoptosis by TA. TA exhibited maximum cytotoxic activity against the Hs 683 cell line. Nuclear morphology, 4',6-diamidino-2-phenylindole staining and annexin V/propidium iodide apoptosis assaying of Hs 683 cells confirmed that cell death was due to the induction of apoptosis by TA. Further mechanistic study of TA on Hs 683 cells revealed that it decreased cell growth with increasing TA concentration, that resulted in the activation of pro-caspase 3 and caspase 9 and the cleavage of poly (ADP-ribose) polymerase, implying the induction of apoptosis cascades. Biochemical evidence of apoptosis resulted from the loss of mitochondrial membrane potential and increased intracellular reactive oxygen species production by TA in a dose-dependent manner. Based on this data, TA may be further investigated as a potential anticancer therapeutic lead.

External auditory exostoses in the Xuchang and Xujiayao human remains: Patterns and implications among eastern Eurasian Middle and Late Pleistocene crania.

In the context of Middle and Late Pleistocene eastern Eurasian human crania, the external auditory exostoses (EAE) of the late archaic Xuchang 1 and 2 and the Xujiayao 15 early Late Pleistocene human temporal bones are described. Xujiayao 15 has small EAE (Grade 1), Xuchang 1 presents bilateral medium EAE (Grade 2), and Xuchang 2 exhibits bilaterally large EAE (Grade 3), especially on the right side. These cranial remains join the other eastern Eurasian later Pleistocene humans in providing frequencies of 61% (N = 18) and 58% (N = 12) respectively for archaic and early modern human samples. These values are near the upper limits of recent human frequencies, and they imply frequent aquatic exposure among these Pleistocene humans. In addition, the medial extents of the Xuchang 1 and 2 EAE would have impinged on their tympanic membranes, and the large EAE of Xuchang 2 would have resulted in cerumen impaction. Both effects would have produced conductive hearing loss, a serious impairment in a Pleistocene foraging context.

Late Pleistocene archaic human crania from Xuchang, China.

Two early Late Pleistocene (~105,000- to 125,000-year-old) crania from Lingjing, Xuchang, China, exhibit a morphological mosaic with differences from and similarities to their western contemporaries. They share pan-Old World trends in encephalization and in supraorbital, neurocranial vault, and nuchal gracilization. They reflect eastern Eurasian ancestry in having low, sagittally flat, and inferiorly broad neurocrania. They share occipital (suprainiac and nuchal torus) and temporal labyrinthine (semicircular canal) morphology with the Neandertals. This morphological combination reflects Pleistocene human evolutionary patterns in general biology, as well as both regional continuity and interregional population dynamics.

The endocranial anatomy of maba 1.

OBJECTIVES: Maba 1, a partial cranium from Guandong Province (China) tentatively dated between 300 and 130 ka, has been suggested to display a mosaic of archaic and derived features, including facial affinities with Neandertals. This study aims to evaluate whether Maba 1 shows a derived endocranial phenotype, or if it displays a plesiomorphic braincase morphology. MATERIALS AND METHODS: We analyzed a set of metric variables on fossil and modern human endocasts using bivariate correlation, principal component analysis, and cluster analyses, to evaluate the morphological affinities of the Maba 1 endocast. RESULTS: The cranial capacity, estimated at around 1300 cc, and the endocranial proportions of Maba 1 are within the ranges of modern humans, Neandertals and Homo heidelbergensis. However, the frontal lobes are narrow and the parietal areas are short and flattened, as in H. heidelbergensis and H. erectus. Nonetheless, the position of the frontal lobes relative to the orbits, the morphology of the frontal sinus and the curve of the frontal squama are more derived, being similar to Neandertals and modern humans. CONCLUSIONS: The endocast displays a general archaic morphology, although with some derived features associated with the spatial relationships with the face. A similar admixture was described for other Middle Pleistocene samples, like Sima de los Huesos. Future phylogenetic studies must re-evaluate the facial skeleton to consider whether its features can be considered as related to the Neandertal lineage. Alternatively, they should be interpreted as the result of homoplasy and parallelism within the genus Homo, and may reflect a predominantly Asian variation. Am J Phys Anthropol 160:633-643, 2016. © 2016 Wiley Periodicals, Inc.

The earliest unequivocally modern humans in southern China.

The hominin record from southern Asia for the early Late Pleistocene epoch is scarce. Well-dated and well-preserved fossils older than ∼45,000 years that can be unequivocally attributed to Homo sapiens are lacking. Here we present evidence from the newly excavated Fuyan Cave in Daoxian (southern China). This site has provided 47 human teeth dated to more than 80,000 years old, and with an inferred maximum age of 120,000 years. The morphological and metric assessment of this sample supports its unequivocal assignment to H. sapiens. The Daoxian sample is more derived than any other anatomically modern humans, resembling middle-to-late Late Pleistocene specimens and even contemporary humans. Our study shows that fully modern morphologies were present in southern China 30,000-70,000 years earlier than in the Levant and Europe. Our data fill a chronological and geographical gap that is relevant for understanding when H. sapiens first appeared in southern Asia. The Daoxian teeth also support the hypothesis that during the same period, southern China was inhabited by more derived populations than central and northern China. This evidence is important for the study of dispersal routes of modern humans. Finally, our results are relevant to exploring the reasons for the relatively late entry of H. sapiens into Europe. Some studies have investigated how the competition with H. sapiens may have caused Neanderthals' extinction (see ref. 8 and references therein). Notably, although fully modern humans were already present in southern China at least as early as ∼80,000 years ago, there is no evidence that they entered Europe before ∼45,000 years ago. This could indicate that H. neanderthalensis was indeed an additional ecological barrier for modern humans, who could only enter Europe when the demise of Neanderthals had already started.

Temporal labyrinths of eastern Eurasian Pleistocene humans.

One of the morphological features that has been identified as uniquely derived for the western Eurasian Neandertals concerns the relative sizes and positions of their semicircular canals. In particular, they exhibit a relatively small anterior canal, a relatively larger lateral one, and a more inferior position of the posterior one relative to the lateral one. These discussions have not included full paleontological data on eastern Eurasian Pleistocene human temporal labyrinths, which have the potential to provide a broader context for assessing Pleistocene Homo trait polarities. We present the temporal labyrinths of four eastern Eurasian Pleistocene Homo, one each of Early (Lantian 1), Middle (Hexian 1), and Late (Xujiayao 15) Pleistocene archaic humans and one early modern human (Liujiang 1). The labyrinths of the two earlier specimens and the most recent one conform to the proportions seen among western early and recent modern humans, reinforcing the modern human pattern as generally ancestral for the genus Homo. The labyrinth of Xujiayao 15 is in the middle of the Neandertal variation and separate from the other samples. This eastern Eurasian labyrinthine dichotomy occurs in the context of none of the distinctive Neandertal external temporal or other cranial features. As such, it raises questions regarding possible cranial and postcranial morphological correlates of Homo labyrinthine variation, the use of individual "Neandertal" features for documenting population affinities, and the nature of late archaic human variation across Eurasia.

An enlarged parietal foramen in the late archaic Xujiayao 11 neurocranium from Northern China, and rare anomalies among Pleistocene Homo.

We report here a neurocranial abnormality previously undescribed in Pleistocene human fossils, an enlarged parietal foramen (EPF) in the early Late Pleistocene Xujiayao 11 parietal bones from the Xujiayao (Houjiayao) site, northern China. Xujiayao 11 is a pair of partial posteromedial parietal bones from an adult. It exhibits thick cranial vault bones, arachnoid granulations, a deviated posterior sagittal suture, and a unilateral (right) parietal lacuna with a posteriorly-directed and enlarged endocranial vascular sulcus. Differential diagnosis indicates that the perforation is a congenital defect, an enlarged parietal foramen, commonly associated with cerebral venous and cranial vault anomalies. It was not lethal given the individual's age-at-death, but it may have been associated with secondary neurological deficiencies. The fossil constitutes the oldest evidence in human evolution of this very rare condition (a single enlarged parietal foramen). In combination with developmental and degenerative abnormalities in other Pleistocene human remains, it suggests demographic and survival patterns among Pleistocene Homo that led to an elevated frequency of conditions unknown or rare among recent humans.

Dentoalveolar paleopathology of the early modern humans from Zhirendong, South China.

The fragmentary early Late Pleistocene, early modern human remains from Zhirendong, south China, present a suite of dentoalveolar pathologies and anomalies. The lesions include lower molar buccal alveolar resorption (Zhiren 1), massive dental caries in a mandibular molar associated with hypercementosis (Zhiren 2), and bilateral mesial premolar (P3) periapical lesions (granulomata with a probable left abscess) (Zhiren 3). The Zhiren 3 periapical lesions, given their bilaterality and the non-pathological incisor and canine alveoli, suggest dens evaginatus, although absence of the Zhiren 3 dentition prevents full evaluation of this diagnosis. These periodontal abnormalities join a number of similar lesions in Pleistocene humans, of varying severity. The carious lesion is noteworthy, given the rarity of them in the Pleistocene human fossil record. In addition, Zhiren 3 exhibits unilateral P3 rotation and bilateral I1 rotation (winging).

Antemortem trauma and survival in the late Middle Pleistocene human cranium from Maba, South China.

Paleopathological assessment of the late Middle Pleistocene archaic human cranium from Maba, South China, has documented a right frontal squamous exocranially concave and ridged lesion with endocranial protrusion. Differential diagnosis indicates that it resulted from localized blunt force trauma, due to an accident or, more probably, interhuman aggression. As such it joins a small sample of pre-last glacial maximum Pleistocene human remains with probable evidence of humanly induced trauma. Its remodeled condition also indicates survival of a serious pathological condition, a circumstance that is increasingly documented for archaic and modern Homo through the Pleistocene.

Human remains from Zhirendong, South China, and modern human emergence in East Asia.

The 2007 discovery of fragmentary human remains (two molars and an anterior mandible) at Zhirendong (Zhiren Cave) in South China provides insight in the processes involved in the establishment of modern humans in eastern Eurasia. The human remains are securely dated by U-series on overlying flowstones and a rich associated faunal sample to the initial Late Pleistocene, >100 kya. As such, they are the oldest modern human fossils in East Asia and predate by >60,000 y the oldest previously known modern human remains in the region. The Zhiren 3 mandible in particular presents derived modern human anterior symphyseal morphology, with a projecting tuber symphyseos, distinct mental fossae, modest lateral tubercles, and a vertical symphysis; it is separate from any known late archaic human mandible. However, it also exhibits a lingual symphyseal morphology and corpus robustness that place it close to later Pleistocene archaic humans. The age and morphology of the Zhiren Cave human remains support a modern human emergence scenario for East Asia involving dispersal with assimilation or populational continuity with gene flow. It also places the Late Pleistocene Asian emergence of modern humans in a pre-Upper Paleolithic context and raises issues concerning the long-term Late Pleistocene coexistence of late archaic and early modern humans across Eurasia.