The vimentin-tubulin binding site peptide (Vim-TBS.58-81) crosses the plasma membrane and enters the nuclei of human glioma cells

Cell-penetrating peptides (CPPs) can translocate through the plasma membrane and localize in different cell compartments providing a promising delivery system for peptides, proteins, nucleic acids, and other products. Here we describe features of a novel cell-penetrating peptide derived from the intermediate filament protein vimentin, called Vim-TBS.58-81. We show that it enters cells from a glioblastoma line via endocytosis where it distributes throughout the cytoplasm and nucleus. Moreover, when coupled to the pro-apoptogenic peptide P10, it localizes to the nucleus inhibiting cell proliferation. Thus, the Vim-TBS.58-81 peptide represents an effective vector for delivery of peptides and potentially a broad range of cargos to the nucleus

Nouvelles données sur les caractéristiques morphologiques immatures du crâne chez les Homo erectus asiatiques

L’identification des spécimens immatures au sein de l’enregistrement fossile est primordial, aussi bien dans la perspective de déterminer la variabilité adulte des différents taxons, que pour aborder leurs caractéristiques ontogénétiques et phylogénétiques. En ce qui concerne les fossiles asiatiques attribués à Homo erectus, seulement quelques restes crâniens d’individus immatures ont été mis au jour et ces spécimens se distribuent sur une très grande période chronologique. Dans ce contexte, l’objectif de cette étude est, d’une part, de tester la validité des caractères généralement employés pour estimer le stade de développement de ces fossiles ; d’autre part, d’apporter des nouvelles données à notre connaissance des caractéristiques morphologiques immatures du squelette céphalique pour l’espèce Homo erectus. L’utilisation des standards de croissance définis chez l’Homme moderne n’apparaît pas appropriée pour étudier la croissance chez Homo erectus et les critères fréquemment utilisés pour discuter du stade de développement chez cette espèce fossile s’avèrent peu significatifs. En effet, les composantes osseuses internes se dissocient précocement et l’épaisseur crânienne peut atteindre la variabilité adulte à un stade de développement immature chez les fossiles asiatiques. Par ailleurs, les variations de forme et de conformation de l’endocrâne entre les spécimens non adultes et adultes chez Homo erectus suivraient une trajectoire différente de celle qui s’observe au cours de la croissance et du développement chez les Hommes modernes.It is critical to be able to recognize the juvenile specimens within the fossil record in order to determine the adult variability of the different taxa and to approach their ontogenetic and phylogenetic characteristics. Nevertheless, with regard to the Asian fossils assigned to Homo erectus, few cranial remains of juvenile individuals have been unearthed. Furthermore, these individuals are spread over a large chronological duration. Our purpose is to test the validity of the features generally used to estimate the developmental age of these fossils and to convey new information about the juvenile features of the cephalic skeleton in the species Homo erectus. Our results illustrate that growth standards defined for modern humans are not suitable to study the growth and development in Homo erectus. Moreover, the criteria frequently used to determine the development stage in Homo erectus would be barely meaningful. We show that the internal components of the cranial vault would differentiate at an early developmental age, as shown by the Mojokerto child. Similarly, cranial vault thickness would come within the adult range of variation early during growth, as shown for the frontal squama by Ngandong 2. The thickness of the frontal superstructures and of the occipital torus would increase later, but before the adult stage. This modification concerns all the internal components of the bone and principally the diploic layer. Moreover, our results suggest that the growth and development of the Homo erectus brain were different from those of modern humans. The transition from the endocranial shape of Mojokerto to the adult morphology for Homo erectus corresponds to a relative development of the frontal lobes, associated with an antero-posterior extension of the cerebral structures. Finally, the globularity of the brain and of the skull would persist late during the ontogenetic history in Homo erectus. The disappearance of these features would be due to an antero-posterior relative elongation of the endocast and of the cranial vault, as well as anterior enlargement of the frontal superstructures and posterior enlargement of the occipital superstructures

Shared Pattern of Endocranial Shape Asymmetries among Great Apes, Anatomically Modern Humans, and Fossil Hominins

Anatomical asymmetries of the human brain are a topic of major interest because of their link with handedness and cognitive functions. Their emergence and occurrence have been extensively explored in human fossil records to document the evolution of brain capacities and behaviour. We quantified for the first time antero-posterior endocranial shape asymmetries in large samples of great apes, modern humans and fossil hominins through analysis of “virtual” 3D models of skull and endocranial cavity and we statistically test for departures from symmetry. Once based on continuous variables, we show that the analysis of these brain asymmetries gives original results that build upon previous analysis based on discrete traits. In particular, it emerges that the degree of petalial asymmetries differs between great apes and hominins without modification of their pattern. We indeed demonstrate the presence of shape asymmetries in great apes, with a pattern similar to modern humans but with a lower variation and a lower degree of fluctuating asymmetry. More importantly, variations in the position of the frontal and occipital poles on the right and left hemispheres would be expected to show some degree of antisymmetry when population distribution is considered, but the observed pattern of variation among the samples is related to fluctuating asymmetry for most of the components of the petalias. Moreover, the presence of a common pattern of significant directional asymmetry for two components of the petalias in hominids implicates that the observed traits were probably inherited from the last common ancestor of extant African great apes and Homo sapiens

Use of a neurofilament peptide for the treatment of glioma

The present invention provides a new drug to treat malignant glioma, which is the most prevalent type of primary tumor of the central nervous system (CNS). The present invention indeed shows that the isolated NFL-TBS40-63 peptide is highly specific for glioma cells, in which it triggers apoptosis. It is therefore presented here for use in a method for treating malignant glioma. The present invention further relates to the use of the NFL-TBS40-63 peptide for detecting specifically glioma cells either in vivo, or in vitro, or for addressing chemical compounds to said tumor cells

Frontal sinus variation in large samples of extant species of the genera Pan, Gorilla and Homo

Frontal pneumatisation is not present in all primates, and among extant species, ethmoidally-derived frontal sinuses are present only in the genera Pan, Gorilla and Homo. A simple and repeatable method is described here to quantify variation in the shape, size and bilateral variation of the frontal sinuses. This has allowed the first large study of these variables, including analyses of large samples of P. paniscus, P. troglodytes, G. gorilla and of several geographically diverse populations of H. sapiens. Frontal sinus shape and size are potential phylogenetic markers in primate systematics. We suggest that, in contrast to an allometric relationship between endocranial and frontal sinus form in Pan and Gorilla, H. sapiens is autapomorphic in having highly variable, supero-inferiorly large frontal sinuses, whose size is unrestricted by variation in cranial form. However, we also describe differences in frontal pneumatisation between those taxa. H. sapiens differs from the other taxa in having relatively smaller frontal sinuses that are more variable in shape and size. In P. troglodytes, P. paniscus and G. gorilla, the shape and size of frontal pneumatisation correlates positively with the overall size of the braincase. This suggests that the large space available in the bone structures of the non-human primates analysed allows the sinuses to develop under only slight constraint (if any) from surrounding structures. In H. sapiens, a significant correlation is observed between the asymmetry in the anterior extension of the frontal lobes of the brain and the shape and extension of the frontal sinuses. We suggest that the more vertical orientation of the H. sapiens frontal bone, its reduced thickness, the reduction of the supraorbital tori and the increased influence of the frontal lobes appear to have modified the integration between the skull, brain and sinuses in the frontal region in our species compared to our nearest extant relatives. Our results reduce the possibility of a strong functional origin for the variation in size and shape of the frontal sinuses in the primates analysed

The internal cranial anatomy of the Middle Pleistocene Broken Hill 1 cranium

The cranium (Broken Hill 1 or BH1) from the site previously known as Broken Hill, Northern Rhodesia (now Kabwe, Zambia) is one of the best preserved hominin fossils from the mid-Pleistocene. Its distinctive combination of anatomical features, however, makes its taxonomic attribution ambiguous. High resolution microCT, which has not previously been employed for gross morphological studies of this important specimen, allows a precise description of the internal anatomical features of BH1, including the distribution of cranial vault thickness and its 2 internal composition, paranasal pneumatisation, pneumatisation of the temporal bone and endocranial anatomy. Relative to other chronologically and taxonomically relevant specimens, BH1 shows unusually marked paranasal pneumatisation and a fairly thick cranial vault. For many of the features analysed, this fossil does not exhibit the apomorphic conditions observed in either Neandertals or Homo sapiens. Its morphology and the general shape of the brain and of the skull may be partly explained by an allometric relationship relative to the features observed in Homo erectus s.l. However, further research is still necessary to better appreciate the cranial anatomy of BH1 and the role of Homo rhodesiensis/Homo heidelbergensis in the course of human evolution. This paper also deals with more general aspects of scientific practices in palaeoanthropology. In particular, we give precise descriptions of many internal anatomical features of Broken Hill 1, a specimen discovered in 1921. This important and unique dataset will allow independent comparative studies in the future. However, we were limited in our study by the very restricted amount of comparative information available for Homo fossils. In our view, scientific papers dealing with the anatomical description of hominin specimens, both in the case of announcements of new discoveries and of discussions of important specimens found decades ago, should always include qualitative and quantitative data that truly allow for further independent research.CBS and LTB thank the Calleva Foundation and the Human Origins Research Fund for funding

Brain tumour targeting strategies via coated ferrociphenol lipid nanocapsules

In this study, a new active targeting strategy to favour ferrociphenol (FcdiOH) internalisation into brain tumour cells was developed by the use of lipid nanocapsules (LNCs) coated with a cell-internalising peptide (NFL-TBS peptide) that interacts with tubulin-binding sites. In comparison, OX26 murine monoclonal antibodies (OX26-MAb) targeting transferrin receptors were also inserted onto LNC surface. The incorporation of OX26 or peptide did not influence the in vitro antiproliferative effect of FcdiOH-LNCs on the 9L cells since their IC50 values were found in the same range. In vivo, intracerebral administration of OX26-FcdiOH-LNCs or peptide-FcdiOH-LNCs by convection enhanced delivery did not enhance the animal median survival time in comparison with untreated rats (25days). Interestingly, intra-carotid treatment with peptide-FcdiOH-LNCs led to an ameliorated survival time of treated rats with the presence of animals surviving until days 35, 40 and 44. Such results were not obtained with OX26-MAbs, demonstrating the benefit of NFL-TBS peptide as an active ligand for peripheral drug delivery to the brain tumours

Frontal sinuses and human evolution

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species? holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of Homo erectus. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species. Variation in frontal sinus shape and dimensions has high potential for phylogenetic discussion when studying human evolution

Frontal sinuses and human evolution

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species’ holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of Homo erectus. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species