The angular distribution of vertebral trabeculae in modern humans,chimpanzees and the Kebara 2 Neanderthal

Bone is known to remodel to optimize its structure according to its mechanical environment. In particular trabecular arcades are thought to align with the orientations of components of principal strain. This paper presents the application of a novel method for quantifying trabecular orientation to test the hypothesis that hominoid posture and locomotion are reflected in trabecular architecture. Lateral radiographs were taken of vertebrae from the entire thoracolumbar spines of eight modern humans, seven Pan troglodytes and one Neanderthal. The radiographs were digitized and a square region of interest located at the centre of each vertebral body selected. Fourier transforms of the regions of interest were performed and the relative magnitude of the transform in each of 16 angular segments calculated. The simple indices of external vertebral body morphology, wedge angle and aspect ratio, were also calculated from the radiographs.All three species exhibit the same pattern, with the majority of trabeculae oriented either axially or dorsoventrally. This suggests that vertebral mechanical loading is similar in chimpanzees and humans, despite their apparent postural and locomotor differences. Significant differences between the magnitudes of the Fourier transform in the 78.75 degrees and 135 degrees orientations of chimpanzee and human vertebrae were observed in all but the upper thoracic spine. As the magnitudes at these orientations in the Neanderthal correspond more closely to that in the human and the orientational features were unrelated to the external vertebral morphology, the difference between the two magnitudes may well prove to be a useful parameter in future phylogenetic analysis. Modern human spines were found to show a greater variation in the proportions of axial and dorsoventral trabeculae with spinal level than chimpanzees, with the greatest differences observed in the upper thoracic spine and thoracolumbar junction, suggesting an association with postural spinal curves.     

Epistasis and Its Implications for Personal Genetics

The widespread availability of high-throughput genotyping technology has opened the door to the era of personal genetics, which brings to consumers the promise of using genetic variations to predict individual susceptibility to common diseases. Despite easy access to commercial personal genetics services, our knowledge of the genetic architecture of common diseases is still very limited and has not yet fulfilled the promise of accurately predicting most people at risk. This is partly because of the complexity of the mapping relationship between genotype and phenotype that is a consequence of epistasis (gene-gene interaction) and other phenomena such as gene-environment interaction and locus heterogeneity. Unfortunately, these aspects of genetic architecture have not been addressed in most of the genetic association studies that provide the knowledge base for interpreting large-scale genetic association results. We provide here an introductory review of how epistasis can affect human health and disease and how it can be detected in population-based studies. We provide some thoughts on the implications of epistasis for personal genetics and some recommendations for improving personal genetics in light of this complexity.     

Allelic Diversity and Its Implications for the Rate of Adaptation

Genetic variation is usually estimated empirically from statistics based on population gene frequencies, but alternative statistics based on allelic diversity (number of allelic types) can provide complementary information. There is a lack of knowledge, however, on the evolutionary implications attached to allelic-diversity measures, particularly in structured populations. In this article we simulated multiple scenarios of single and structured populations in which a quantitative trait subject to stabilizing selection is adapted to different fitness optima. By forcing a global change in the optima we evaluated which diversity variables are more strongly correlated with both short- and long-term adaptation to the new optima. We found that quantitative genetic variance components for the trait and gene-frequency-diversity measures are generally more strongly correlated with short-term response to selection, whereas allelic-diversity measures are more correlated with long-term and total response to selection. Thus, allelic-diversity variables are better predictors of long-term adaptation than gene-frequency variables. This observation is also extended to unlinked neutral markers as a result of the information they convey on the demographic population history. Diffusion approximations for the allelic-diversity measures in a finite island model under the infinite-allele neutral mutation model are also provided.     

Facial ontogeny in Neanderthals and modern humans

One hundred and fifty years after the discovery of Neanderthals, it is held that this morphologically and genetically distinct human species does not differ from modern Homo sapiens in its craniofacial ontogenetic trajectory after the early post-natal period. This is striking given the evident morphological differences between these species, since it implies that all of the major differences are established by the early post-natal period and carried into adulthood through identical trajectories, despite the extent to which mechanical and spatial factors are thought to influence craniofacial ontogeny. Here, we present statistical and morphological analyses demonstrating that the spatio-temporal processes responsible for craniofacial ontogenetic transformations differ. The findings emphasize that pre-natal as well as post-natal ontogeny are both important in establishing the cranial morphological differences between adult Neanderthals and modern humans.     

Bitter taste perception in Neanderthals through the analysis of the TAS2R38 gene

The bitter taste perception (associated with the ability or inability to taste phenylthiocarbamide) is mediated by the TAS2R38 gene. Most of the variation in this gene is explained by three common amino-acid polymorphisms at positions 49 (encoding proline or alanine), 262 (alanine or valine) and 296 (valine or isoleucine) that determine two common isoforms: proline–alanine–valine (PAV) and alanine–valine–isoleucine (AVI). PAV is the major taster haplotype (heterozygote and homozygote) and AVI is the major non-taster haplotype (homozygote). Amino acid 49 has the major effect on the distinction between tasters and non-tasters of all three variants. The sense of bitter taste protects us from ingesting toxic substances, present in some vegetables, that can affect the thyroid when ingested in large quantities. Balancing selection has been used to explain the current high non-taster frequency, by maintaining divergent TAS2R38 alleles in humans. We have amplified and sequenced the TAS2R38 amino acid 49 in the virtually uncontaminated Neanderthal sample of El Sidrón 1253 and have determined that it was heterozygous. Thus, this Neanderthal was a taster individual, although probably slightly less than a PAV homozygote. This indicates that variation in bitter taste perception pre-dates the divergence of the lineages leading to Neanderthals and modern humans.     

Young Children Understand the Normative Implications of Future-Directed Speech Acts

Much recent research has shown that the capacity for mental time travel and temporal reasoning emerges during the preschool years. Nothing is known so far, however, about young children''s grasp of the normative dimension of future-directed thought and speech. The present study is the first to show that children from age 4 understand the normative outreach of such future-directed speech acts: subjects at time 1 witnessed a speaker make future-directed speech acts about/towards an actor A, either in imperative mode (“A, do X!”) or as a prediction (“the actor A will do X”). When at time 2 the actor A performed an action that did not match the content of the speech act at time 1, children identified the speaker as the source of a mistake in the prediction case, and the actor as the source of the mistake in the imperative case and leveled criticism accordingly. These findings add to our knowledge about the emergence and development of temporal cognition in revealing an early sensitivity to the normative aspects of future-orientation.     

Visual Speech Perception in Foveal and Extrafoveal Vision: Further Implications for Divisions in Hemispheric Projections

When observing a talking face, it has often been argued that visual speech to the left and right of fixation may produce differences in performance due to divided projections to the two cerebral hemispheres. However, while it seems likely that such a division in hemispheric projections exists for areas away from fixation, the nature and existence of a functional division in visual speech perception at the foveal midline remains to be determined. We investigated this issue by presenting visual speech in matched hemiface displays to the left and right of a central fixation point, either exactly abutting the foveal midline or else located away from the midline in extrafoveal vision. The location of displays relative to the foveal midline was controlled precisely using an automated, gaze-contingent eye-tracking procedure. Visual speech perception showed a clear right hemifield advantage when presented in extrafoveal locations but no hemifield advantage (left or right) when presented abutting the foveal midline. Thus, while visual speech observed in extrafoveal vision appears to benefit from unilateral projections to left-hemisphere processes, no evidence was obtained to indicate that a functional division exists when visual speech is observed around the point of fixation. Implications of these findings for understanding visual speech perception and the nature of functional divisions in hemispheric projection are discussed.     

Browridge structure and function in extant primates and Neanderthals

The structural characteristics of the supraorbital ridge in three extent primate species and fossil Neanderthals are described in this study. Surface morphology and patterns of trabecular organization as observed in cross-sectional collections of Papio, Macaca and Pan are compared with similar traits encountered in the Pech de l'Aze infant, Gibraltar child, and La Quina 5, La Chapelle-aux-Saints, Broken Hill, Skhul V, Skhul IX, Tabun I and Gibraltar adult Neanderthals. Periods of rapid appositional growth of the browridges by means of fine cancellous bone formation and its subsequent remodeling and consolidation are temporally correlated with dental development and eruption sequences.     

Purine Metabolism in Pigs and Humans and Its Implications for Xenotransplantation

We compared concentrations of nucleotide substrates and activities of enzymes of nucleotide metabolism in pig and human blood, heart, and kidney. The most important difference was lower ecto-5′-nucleotidase (E5′N) activity in both pig hearts and kidney. Furthermore, higher hypoxanthine, inosine, adenine, and uracil, but lower uridine and uric acid concentrations were observed in pig blood as compared to human. A twofold increase in UTP concentration has been observed in pig hearts following 4 h perfusion with human blood. Purine metabolism is an important target for genetic and pharmacological manipulation during xenotransplantations.     

Bacteriology of the Gut and Its Clinical Implications

The bacteriology of the gastrointestinal tract is rapidly changing in laboratory techniques and clinical correlations. The flora is found to be very complex, predominantly anaerobic, and importantly dependent on diet. An etiologic role for colon bacteria in colon cancer is suggested by correlations between epidemiologic data and prevalent dietary patterns and stool culture findings. Cultures from aspiration pneumonia, subphrenic abscess, and other intra-abdominal sepsis all yield anaerobes, and for best results antibiotic therapy should combat them as well as aerobes.     

Microbial Iron Oxidation in the Arctic Tundra and Its Implications for Biogeochemical Cycling

The role that neutrophilic iron-oxidizing bacteria play in the Arctic tundra is unknown. This study surveyed chemosynthetic iron-oxidizing communities at the North Slope of Alaska near Toolik Field Station (TFS) at Toolik Lake (lat 68.63, long −149.60). Microbial iron mats were common in submerged habitats with stationary or slowly flowing water, and their greatest areal extent is in coating plant stems and sediments in wet sedge meadows. Some Fe-oxidizing bacteria (FeOB) produce easily recognized sheath or stalk morphotypes that were present and dominant in all the mats we observed. The cool water temperatures (9 to 11°C) and reduced pH (5.0 to 6.6) at all sites kinetically favor microbial iron oxidation. A microbial survey of five sites based on 16S rRNA genes found a predominance of Proteobacteria, with Betaproteobacteria and members of the family Comamonadaceae being the most prevalent operational taxonomic units (OTUs). In relative abundance, clades of lithotrophic FeOB composed 5 to 10% of the communities. OTUs related to cyanobacteria and chloroplasts accounted for 3 to 25% of the communities. Oxygen profiles showed evidence for oxygenic photosynthesis at the surface of some mats, indicating the coexistence of photosynthetic and FeOB populations. The relative abundance of OTUs belonging to putative Fe-reducing bacteria (FeRB) averaged around 11% in the sampled iron mats. Mats incubated anaerobically with 10 mM acetate rapidly initiated Fe reduction, indicating that active iron cycling is likely. The prevalence of iron mats on the tundra might impact the carbon cycle through lithoautotrophic chemosynthesis, anaerobic respiration of organic carbon coupled to iron reduction, and the suppression of methanogenesis, and it potentially influences phosphorus dynamics through the adsorption of phosphorus to iron oxides.     

The Regulation of the Autophagic Network and Its Implications for Human Disease

Autophagy has attracted a lot of attention in recent years. More and more proteins and signaling pathways have been discovered that somehow feed into the autophagy regulatory pathways. Regulation of autophagy is complex and condition-specific, and in several diseases, autophagic fluxes are changed. Here, we review the most well-established concepts in this field as well as the reported signaling pathways or components which steer the autophagy machinery. Furthermore, we will highlight how autophagic fluxes are changed in various diseases either as cause for or as response to deal with an altered cellular homeostasis and how modulation of autophagy might be used as potential therapy for such diseases.     

The Discovery of Human of GLUD2 Glutamate Dehydrogenase and Its Implications for Cell Function in Health and Disease

While the evolutionary changes that led to traits unique to humans remain unclear, there is increasing evidence that enrichment of the human genome through DNA duplication processes may have contributed to traits such as bipedal locomotion, higher cognitive abilities and language. Among the genes that arose through duplication in primates during the period of increased brain development was GLUD2, which encodes the hGDH2 isoform of glutamate dehydrogenase expressed in neural and other tissues. Glutamate dehydrogenase GDH is an enzyme central to the metabolism of glutamate, the main excitatory neurotransmitter in mammalian brain involved in a multitude of CNS functions, including cognitive processes. In nerve tissue GDH is expressed in astrocytes that wrap excitatory synapses, where it is thought to play a role in the metabolic fate of glutamate removed from the synaptic cleft during excitatory transmission. Expression of GDH rises sharply during postnatal brain development, coinciding with nerve terminal sprouting and synaptogenesis. Compared to the original hGDH1 (encoded by the GLUD1 gene), which is potently inhibited by GTP generated by the Krebs cycle, hGDH2 can function independently of this energy switch. In addition, hGDH2 can operate efficiently in the relatively acidic environment that prevails in astrocytes following glutamate uptake. This adaptation is thought to provide a biological advantage by enabling enhanced enzyme catalysis under intense excitatory neurotransmission. While the novel protein may help astrocytes to handle increased loads of transmitter glutamate, dissociation of hGDH2 from GTP control may render humans vulnerable to deregulation of this enzyme’s function. Here we will retrace the cloning and characterization of the novel GLUD2 gene and the potential implications of this discovery in the understanding of mechanisms that permitted the brain and other organs that express hGDH2 to fine-tune their functions in order to meet new challenging demands. In addition, the potential role of gain-of-function of hGDH2 variants in human neurodegenerative processes will be considered.     

Variation in Lithic Technological Strategies among the Neanderthals of Gibraltar

The evidence for Neanderthal lithic technology is reviewed and summarized for four caves on The Rock of Gibraltar: Vanguard, Beefsteak, Ibex and Gorham’s. Some of the observed patterns in technology are statistically tested including raw material selection, platform preparation, and the use of formal and expedient technological schemas. The main parameters of technological variation are examined through detailed analysis of the Gibraltar cores and comparison with samples from the classic Mousterian sites of Le Moustier and Tabun C. The Gibraltar Mousterian, including the youngest assemblage from Layer IV of Gorham’s Cave, spans the typical Middle Palaeolithic range of variation from radial Levallois to unidirectional and multi-platform flaking schemas, with characteristic emphasis on the former. A diachronic pattern of change in the Gorham’s Cave sequence is documented, with the younger assemblages utilising more localized raw material and less formal flaking procedures. We attribute this change to a reduction in residential mobility as the climate deteriorated during Marine Isotope Stage 3 and the Neanderthal population contracted into a refugium.     

Examining the Extinction of the Barbary Lion and Its Implications for Felid Conservation

Estimations of species extinction dates are rarely definitive, yet declarations of extinction or extirpation are important as they define when conservation efforts may cease. Erroneous declarations of extinctions not only destabilize conservation efforts but also corrode local community support. Mismatches in perceptions by the scientific and local communities risk undermining sensitive, but important partnerships. We examine observations relating to the decline and extinction of Barbary lions in North Africa. Whilst the extinction predates the era of the scientific conservation movement, the decline is relatively well documented in historical records. Recently unearthed accounts suggest Barbary lions survived later than previously assumed. We use probabilistic methods to estimate a more recent extinction date for the subspecies. The evidence presented for a much later persistence of lions in North Africa, including generations when sightings were nil, suggests caution when considering felid populations as extinct in the wild. The case raises the possibility that captive animals descended from the Moroccan royal collection are closer contemporaries to wild Barbary lions. Furthermore, our results highlight the vulnerability of very small lion populations and the significance of continued conservation of remnant lion populations in Central and West Africa.