192 research outputs found

    Palaeoanthropology - Sahelanthropus or 'Sahelpithecus'?

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62951/1/419581a.pd

    Early Origin for Human-Like Precision Grasping: A Comparative Study of Pollical Distal Phalanges in Fossil Hominins

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    Altres ajuts: Generalitat de Catalunya 2006 FI 00065 i beca de viatge 2008 BE1 00370Background: The morphology of human pollical distal phalanges (PDP) closely reflects the adaptation of human hands for refined precision grip with pad-to-pad contact. The presence of these precision grip-related traits in the PDP of fossil hominins has been related to human-like hand proportions (i.e. short hands with a long thumb) enabling the thumb and finger pads to contact. Although this has been traditionally linked to the appearance of stone tool-making, the alternative hypothesis of an earlier origin-related to the freeing of the hands thanks to the advent of terrestrial bipedalism-is also possible given the human-like intrinsic hand proportion found in australopiths. - Methodology/Principal Findings: We perform morphofunctional and morphometric (bivariate and multivariate) analyses of most available hominin pollical distal phalanges, including Orrorin, Australopithecus, Paranthropous and fossil Homo, in order to investigate their morphological affinities. Our results indicate that the thumb morphology of the early biped Orrorin is more human-like than that of australopiths, in spite of its ancient chronology (ca. 6 Ma). Moreover, Orrorin already displays typical human-like features related to precision grasping. - Conclusions: These results reinforce previous hypotheses relating the origin of refined manipulation of natural objects-not stone tool-making-with the relaxation of locomotor selection pressures on the forelimbs. This suggests that human hand length proportions are largely plesiomorphic, in the sense that they more closely resemble the relatively short-handed Miocene apes than the elongated hand pattern of extant hominoids. With the advent of terrestrial bipedalism, these hand proportions may have been co-opted by early hominins for enhanced manipulative capabilities that, in turn, would have been later co-opted for stone tool-making in the genus Homo, more encephalized than the previous australopiths. This hypothesis remains may be further tested by the finding of more complete hands of unequivocally biped early hominins

    Activation of p38MAPK Contributes to Expanded Polyglutamine-Induced Cytotoxicity

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    The signaling pathways that may modulate the pathogenesis of diseases induced by expanded polyglutamine proteins are not well understood.Herein we demonstrate that expanded polyglutamine protein cytotoxicity is mediated primarily through activation of p38MAPK and that the atypical PKC iota (PKCiota) enzyme antagonizes polyglutamine-induced cell death through induction of the ERK signaling pathway. We show that pharmacological blockade of p38MAPK rescues cells from polyglutamine-induced cell death whereas inhibition of ERK recapitulates the sensitivity observed in cells depleted of PKCiota by RNA interference. We provide evidence that two unrelated proteins with expanded polyglutamine repeats induce p38MAPK in cultured cells, and demonstrate induction of p38MAPK in an in vivo model of neurodegeneration (spinocerebellar ataxia 1, or SCA-1).Taken together, our data implicate activated p38MAPK in disease progression and suggest that its inhibition may represent a rational strategy for therapeutic intervention in the polyglutamine disorders

    †Kenyaichthyidae fam. nov and †Kenyaichthys gen. nov - First Record of a Fossil Aplocheiloid Killifish (Teleostei, Cyprinodontiformes)

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    The extant Cyprinodontiformes (killifishes) with their two suborders Cyprinodontoidei and Aplocheiloidei represent a diverse and well-studied group of fishes. However, their fossil record is comparatively sparse and has so far yielded members of the Cyprinodontoidei only. Here we report on cyprinodontiform fossils from the upper Miocene Lukeino Formation in the Tugen Hills of the Central Rift Valley of Kenya, which represent the first fossil record of an aplocheiloid killifish. A total of 169 specimens - mostly extraordinarily well preserved and a sample of ten extant cyprinodontiform species were studied on the basis of morphometrics, meristics and osteology. A phylogenetic analysis using PAUP was also conducted for the fossils. Both the osteological data and the phylogenetic analysis provide strong evidence for the assignment of the fossils to the Aplocheiloidei, and justify the definition of the new family dagger Kenyaichthyidae, the new genus dagger Kenyaichthys and the new species dagger K. kipkechi sp. nov. The phylogenetic analysis unexpectedly places dagger Kenyaichthys gen. nov. in a sister relationship to the Rivulidae (a purely Neotropical group),a probable explanation might be lack of available synapomorphies for the Rivulidae, Nothobranchiidae and Aplocheilidae. The specimens of dagger K. kipkechi sp. nov. show several polymorphic characters and large overlap in meristic traits, which justifies their interpretation as a species flock in statu nascendi. Patterns of variation in neural and haemal spine dimensions in the caudal vertebrae of dagger Kenyaichthys gen. nov. and the extant species studied indicate that some previously suggested synapomorphies of the Cyprinodontoidei and Aplocheiloidei need to be revised

    Designer Gene Delivery Vectors: Molecular Engineering and Evolution of Adeno-Associated Viral Vectors for Enhanced Gene Transfer

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    Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells, and sustained maintenance of the viral genome. However, several problems should be addressed to enhance the utility of AAV vectors, particularly those based on AAV2, the best characterized AAV serotype. First, altering viral tropism would be advantageous for broadening its utility in various tissue or cell types. In response to this need, vector pseudotyping, mosaic capsids, and targeting ligand insertion into the capsid have shown promise for altering AAV specificity. In addition, library selection and directed evolution have recently emerged as promising approaches to modulate AAV tropism despite limited knowledge of viral structure–function relationships. Second, pre-existing immunity to AAV must be addressed for successful clinical application of AAV vectors. “Shielding” polymers, site-directed mutagenesis, and alternative AAV serotypes have shown success in avoiding immune neutralization. Furthermore, directed evolution of the AAV capsid is a high throughput approach that has yielded vectors with substantial resistance to neutralizing antibodies. Molecular engineering and directed evolution of AAV vectors therefore offer promise for generating ‘designer’ gene delivery vectors with enhanced properties

    First Early Hominin from Central Africa (Ishango, Democratic Republic of Congo)

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    Despite uncontested evidence for fossils belonging to the early hominin genus Australopithecus in East Africa from at least 4.2 million years ago (Ma), and from Chad by 3.5 Ma, thus far there has been no convincing evidence of Australopithecus, Paranthropus or early Homo from the western (Albertine) branch of the Rift Valley. Here we report the discovery of an isolated upper molar (#Ish25) from the Western Rift Valley site of Ishango in Central Africa in a derived context, overlying beds dated to between ca. 2.6 to 2.0 Ma. We used µCT imaging to compare its external and internal macro-morphology to upper molars of australopiths, and fossil and recent Homo. We show that the size and shape of the enamel-dentine junction (EDJ) surface discriminate between Plio-Pleistocene and post-Lower Pleistocene hominins, and that the Ishango molar clusters with australopiths and early Homo from East and southern Africa. A reassessment of the archaeological context of the specimen is consistent with the morphological evidence and suggest that early hominins were occupying this region by at least 2 Ma

    Evidence of a chimpanzee-sized ancestor of humans but a gibbon-sized ancestor of apes

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    Body mass directly affects how an animal relates to its environment and has a wide range of biological implications. However, little is known about the mass of the last common ancestor (LCA) of humans and chimpanzees, hominids (great apes and humans), or hominoids (all apes and humans), which is needed to evaluate numerous paleobiological hypotheses at and prior to the root of our lineage. Here we use phylogenetic comparative methods and data from primates including humans, fossil hominins, and a wide sample of fossil primates including Miocene apes from Africa, Europe, and Asia to test alternative hypotheses of body mass evolution. Our results suggest, contrary to previous suggestions, that the LCA of all hominoids lived in an environment that favored a gibbon-like size, but a series of selective regime shifts, possibly due to resource availability, led to a decrease and then increase in body mass in early hominins from a chimpanzee-sized LCA
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