Substituents effects on activity of kynureninase from Homo sapiens and Pseudomonas fluorescens

A series of substituted kynurenines (3-bromo-dl, 3-chloro-dl, 3-fluoro-dl, 3-methyl-dl, 5-bromo-l, 5-chloro-l, 3,5-dibromo-l and 5-bromo-3-chloro-dl) have been synthesized and tested for their substrate activity with human and Pseudomonas fluorescens kynureninase. All of the substituted kynurenines examined have substrate activity with both human as well as P. fluorescens kynureninase. For the human enzyme, 3- and 5-substituted kynurenines have k_cat and k_cat/K_m values higher than l-kynurenine, but less than that of the physiological substrate, 3-hydroxykynurenine. However, 3,5-dibromo- and 5-bromo-3-chlorokynurenine have k_cat and k_cat/K_m values close to that of 3-hydroxykynurenine with human kynureninase. The effects of the 3-halo substituents on the reactivity with human kynureninase may be due to electronic effects and/or halogen bonding. In contrast, for the bacterial enzyme, 3-methyl, 3-halo and 3,5-dihalokynurenines are much poorer substrates, while 3-fluoro, 5-bromo, and 5-chlorokynurenine have k_cat and k_cat/K_m values comparable to that of its physiological substrate, l-kynurenine. Thus, 5-bromo and 5-chloro-l-kynurenine are good substrates for both human as well as bacterial enzyme, indicating that both enzymes have space for substituents in the active site near C-5. The increased activity of the 5-halokynurenines may be due to van der Waals contacts or hydrophobic effects. These results may be useful in the design of potent and/or selective inhibitors of human and bacterial kynureninase.     

Crystal structure of Homo sapiens PTD012 reveals a zinc-containing hydrolase fold

The human protein PTD012 is the longer product of an alternatively spliced gene and was described to be localized in the nucleus. The X-ray structure analysis at 1.7 A resolution of PTD012 through SAD phasing reveals a monomeric protein and a novel fold. The shorter splice form was also studied and appears to be unfolded and non-functional. The structure of PTD012 displays an alphabetabetaalpha four-layer topology. A metal ion residing between the central beta-sheets is partially coordinated by three histidine residues. X-ray absorption near-edge structure (XANES) analysis identifies the PTD012-bound ion as Zn(2+). Tetrahedral coordination of the ion is completed by the carboxylate oxygen atom of an acetate molecule taken up from the crystallization buffer. The binding of Zn(2+) to PTD012 is reminiscent of zinc-containing enzymes such as carboxypeptidase, carbonic anhydrase, and beta-lactamase. Biochemical assays failed to demonstrate any of these enzyme activities in PTD012. However, PTD012 exhibits ester hydrolase activity on the substrate p-nitrophenyl acetate.     

Becoming Modern Homo sapiens

Human beings are unusual in many ways but perhaps most strikingly in their unique symbolic form of processing information about the world around them. Although based on a long and essential evolutionary history, the modern human cognitive style is not predicted by that history: it is emergent rather than the product of an incremental process of refinement. Homo sapiens is physically very distinctive and is clearly the result of a significant developmental reorganization with ramifications throughout the skeleton and presumably beyond. It is reasonable to suppose that the neural underpinnings of symbolic thought were acquired in this reorganization. However, the fossil and archeological records indicate that the first anatomically recognizable members of the species substantially predated its first members who behaved in a demonstrably symbolic manner. Thus, while the biological potential for symbolic thinking most likely arose in the morphogenetic event that gave rise to H. sapiens as a distinctive anatomical entity, this new capacity was evidently exaptive, in the sense that it had to await its “discovery” and release through a cultural stimulus. Plausibly, this stimulus was the invention of language. One expression of symbolic reasoning is the adoption of technological change in response to environmental challenges, contrasting with earlier responses that typically involved using existing technologies in new ways. As climates changed at the end of the last Ice Age, the new technophile proclivity was expressed in a shift toward agriculture and sedentary lifestyles: a shift that precipitated a fundamentally new (and potentially self-destructive) relationship with nature. Thus, both of what are arguably the two most radical (and certainly the most fateful) evolutionary innovations in the history of life (symbolic thinking and sedentary lifestyles) were both very recent occurrences, well within the (so far rather short) tenure of H. sapiens.     

The rise and fall of Homo sapiens sapiens

Human beings have broken the ecological 'law' that says that big, predatory animals are rare. Two crucial innovations in particular have enabled us to alter the planet to suit ourselves and thus permit unparalleled expansion: speech (which implies instant transmission of an open-ended range of conscious thoughts) and agriculture (which causes the world to produce more human food than unaided nature would do). However, natural selection has not equipped us with a long-term sense of self-preservation. Our population cannot continue to expand at its present rate for much longer, and the examples of many other species suggests that expansion can end in catastrophic collapse. Survival beyond the next century in a tolerable state seems most unlikely unless all religions and economies begin to take account of the facts of biology. This, if it occurred, would be a step in cultural evolution that would compare in import with the birth of agriculture.     

Population structure and the evolution of Homo sapiens in Africa

It has been proposed that a multiregional model could describe how Homo sapiens evolved in Africa beginning 300,000 years ago. Multiregionalism would require enduring morphological or behavioral differences among African regions and morphological or behavioral continuity within each. African fossils, archeology, and genetics do not comply with either requirement and are unlikely to, because climatic change periodically disrupted continuity and reshuffled populations. As an alternative to multiregionalism, I suggest that reshuffling produced novel gene constellations, including one in which the additive or cumulative effect of newly associated genes enhanced cognitive or communicative potential. Eventual fixation of such a constellation in the lineage leading to modern H. sapiens would explain the abrupt appearance of the African Later Stone Age 50–45 thousand years ago, its nearly simultaneous expansion to Eurasia in the form of the Upper Paleolithic, and the ability of fully modern Upper Paleolithic people to swamp or replace non‐modern Eurasians.     

Tooth components of mandibular deciduous molars of Homo sapiens sapiens and Homo sapiens neanderthalensis: a radiographic study.

Tooth components of deciduous molars were measured from standardized radiographs of Homo sapiens sapiens and Homo sapiens neanderthalensis. Enamel height and width were greater in deciduous teeth of Homo sapiens sapiens than in Homo sapiens neanderthalensis and the differences were statistically significant (p less than 0.01). Dentin height showed no significant differences between the two groups, but enamel to floor of pulp chamber and pulp height and width dimensions were significantly greater in Homo sapiens neanderthalensis. Discriminant analysis carried out between groups, using deciduous tooth components, showed an accuracy of 98-100% for identification of Homo sapiens sapiens and 83-92% for identification of Homo sapiens neanderthalensis. The results obtained in this study on dental dimensions support the hypothesis of a distinct evolutionary line for Neanderthals.     

X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880

The human protein FLJ36880 belongs to the fumarylacetoacetate hydrolase family. The X-ray structure of FLJ36880 has been determined to 2.2 A resolution employing the semi-automated high-throughput structural genomics approach of the Protein Structure Factory. FLJ36880 adopts a mixed beta-sandwich roll fold and forms homodimers in crystals as well as in solution. One Mg2+ ion is bound to each subunit of the dimeric protein by coordination to three carboxylate oxygens and three water molecules. These metal binding sites are accessible from the same surface of the dimer, partly due to the disorder of the undecapeptide stretch D29 to L39. The overall structure and metal binding site of FLJ36880 bear clear similarities to the C-terminal domain of the bifunctional enzyme HpcE from Escherichia coli C, fumarylacetoacetate hydrolase from Mus musculus and to YcgM (Apc5008) from E. coli 1262. These similarities provide a framework for suggesting biochemical functions and evolutionary relationships of FLJ36880. It appears highly probable that the metal binding sites are involved in an enzymatic activity related to the catabolism of aromatic amino acids. Two point mutations in the active-site of FAH, responsible for the metabolic disease hereditary tyrosinemia type I (HTI) in humans, affect residues that are structurally conserved in FLJ36880 and located in the putative catalytic site.     

Evolution of nakedness in Homo sapiens

Homo sapiens L. is the only existing primate species lacking in functionally effective thermally insulating fur. As all other primates have considerable hair covering, it has always been accepted that our ancestors must once have had a respectable amount of body hair. Unfortunately, fossils cannot help us when it comes to differences in skin and hair. Recent DNA analysis, however, has given us some idea of when and where the great denudation took place. A number of hypotheses have been proposed to account for this feature, but none of these has gained general acceptance. In this paper, I present these hypotheses in the light of current empirical evidence and discussion.     

The Exploitation of Ungulate Bones in Homo neanderthalensis and Homo sapiens

Analysis of ungulate bones recovered from a number of Upper and Middle Palaeolithic sites in southern Italy revealed differences in the presence of anatomical elements. There is a lack of clear evidence of carnivore activities, and differences can be attributed to human activity. Indeed, these differences were probably due to different patterns of skeletal exploitation between Homo neanderthalensis and H. sapiens. Small limb bones (carpals, tarsals, sesamoids, long bone epiphyses and especially phalanges) are rarely found in Middle Palaeolithic deposits, but are abundant in the Upper Palaeolithic. The observation of unidentified bone fragments at these sites indicates that during the middle Palaeolithic, marrow extraction regarded essentially the treatment of long bones. First and second phalanges were not frequently used for this practice, but they were often fragmented by H. sapiens. Lack of these bones among the remains of meals of Neanderthal suggests that these bones were probably destroyed by their utilisation as fuel.     

Cranial capacity evolution in Homo erectus and early Homo sapiens.

This paper investigates patterns of cranial capacity evolution in Homo erectus, early Homo sapiens, and in regional subsamples of H. erectus. Specifically, models explaining evolution of cranial capacity in these taxa are evaluated with statistical techniques developed for the analysis of time series data. Regression estimates of rates of evolution in cranial capacity are also obtained. A non-parametric test for trend suggests that cranial capacity in both H. erectus and early H. sapiens may increase significantly through time. Cranial capacity in an Asian subsample of H. erectus (comprised of Chinese and Indonesian specimens) increases significantly through time. Other subsamples of H. erectus (African, Chinese, and Indonesian) do not appear to increase significantly through time. Regression results generally corroborate results of the test for trend. Spatial and temporal variation may characterize evolution of cranial capacity in H. erectus. Different patterns of cranial capacity evolution may distinguish H. erectus from early H. sapiens.     

Vigilance and Group Size in Homo sapiens

While eating, Homo sapiens frequently look up and visually scan their environment. As in many bird and mammal species studied, the frequency of looking up was negatively correlated with group size. Average duration of scanning the environment also correlated negatively with group size. At all group sizes studied (1–5), females spent less time scanning than did males. With increasing group size females reduced their rate of looking up more than did males.     

Solution structure of a membrane-anchored ubiquitin-fold (MUB) protein from Homo sapiens

The protein Bc059385, whose solution structure is reported here, is the human representative of a recently identified family of membrane-anchored ubiquitin-fold (MUB) proteins. Analysis of their similarity to ubiquitin indicates that homologous amino acid residues in MUBs form a hydrophobic surface very similar to the recognition patch surrounding Ile-44 in ubiquitin. This suggests that MUBs may interact with proteins containing an alpha-helical motif similar to those of some ubiquitin binding domains. A disordered loop common to MUBs may also provide a second protein interaction site. From the available data, it is probable that this protein is prenylated and associated with the membrane. With <20% identity to ubiquitin, the MUB family further expands the sequence space that maps to the beta-grasp fold, and adds membrane localization to its list of functional roles.     

Yawn contagion and empathy in Homo sapiens

The ability to share others' emotions, or empathy, is crucial for complex social interactions. Clinical, psychological, and neurobiological clues suggest a link between yawn contagion and empathy in humans (Homo sapiens). However, no behavioral evidence has been provided so far. We tested the effect of different variables (e.g., country of origin, sex, yawn characteristics) on yawn contagion by running mixed models applied to observational data collected over 1 year on adult (>16 years old) human subjects. Only social bonding predicted the occurrence, frequency, and latency of yawn contagion. As with other measures of empathy, the rate of contagion was greatest in response to kin, then friends, then acquaintances, and lastly strangers. Related individuals (r≥0.25) showed the greatest contagion, in terms of both occurrence of yawning and frequency of yawns. Strangers and acquaintances showed a longer delay in the yawn response (latency) compared to friends and kin. This outcome suggests that the neuronal activation magnitude related to yawn contagion can differ as a function of subject familiarity. In conclusion, our results demonstrate that yawn contagion is primarily driven by the emotional closeness between individuals and not by other variables, such as gender and nationality.     

Hypertrophy of the acetabulo-cristal buttress in Homo sapiens

In the early 1970s, excavation at the King site, a contact period Mississippian village in northwest Georgia, yielded the skeletal remains of a robust male (King 65) possessing marked hypertrophy of the acetabulo-cristal buttress. The buttress is morphologically similar to that of Plio-Pleistocene Homo but it is accompanied by an anatomically modern degree of thickening of the gluteal table of the ilium. Although the degree of cortical thickness of the gluteal table of the ilium is apparently species-specific, hypertrophy of the acetabulo-cristal buttress is developmental and may be expressed in all species of Homo. © 1993 Wiley-Liss, Inc.