Yolk proteins of Caenorhabditis elegans

A group of proteins judged on several criteria to be yolk proteins have been isolated from a homogenate of the nematode Caenorhabditis elegans. Comparison of partial proteolysis fragments indicates that the two bands of a 170,000-dalton doublet (yp170) are closely related; bands observed at 115,000 daltons (yp115) and 88,000 daltons (yp88) appear to be structurally distinct. All three yolk protein species are glycoproteins, as judged by binding of the lectin concanavalin A. The yp170 doublet has been purified by gel filtration in the presence of sodium dodecyl sulfate. An antiserum obtained by immunization with the purified yp170 doublet does not bind either of the two smaller proteins. Staining of C. elegans eggs by indirect immunofluorescence with the anti-yp170 serum indicates a dispersed cytoplasmic location for the antigen throughout embryogenesis, with apparent segregation to the intestine immediately prior to hatching.     

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.     

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.     

The complete complement of C1q-domain-containing proteins in Homo sapiens

The C-terminal domains of the A, B, C chains of C1q subcomponent of C1 complex represent a common structural motif, the C1q domain, that is found in a diverse range of proteins. We analyzed the human genome for the complete complement of this family and have identified a total of 31 independent gene sequences. The predominant organization of C1q-domain-containing (C1qDC) proteins includes a leading signal peptide, a collagen-like region of variable length, and a C-terminal C1q domain. There are 15 highly conserved residues within the C1q domain, among which 8 are invariant within the human gene set and these are predicted to cluster within the hydrophobic core of the protein. We suggest a 3-subfamily classification based on sequence homology. For some C1qDC-encoding genes, strict orthology has been retained throughout vertebrate evolution and these examples suggest a highly specific functional role for C1qDC proteins that has been under significant selective pressure. Alternatively, individual species have co-opted C1qDC proteins for roles that are highly specific to their biology, suggesting an evolutionary strategy of gene duplication and functional diversification. A more extensive analysis of the evolutionary relationship of C1qDC proteins reveals an ancient rooting, with clear members found in eubacterial species. Curiously, we have been unable to identify C1qDC-encoding genes in many eukaryotic genomcs, such as Sacchromyces cerivisae and C. elegans, suggesting that the retention or loss of this gene family throughout evolution has been sporadic.     

N-Glycans of Caenorhabditis elegans are specific to developmental stages

We have examined the N-glycans present during the developmental stages of Caenorhabditis elegans using two approaches, 1) a combination of permethylation followed by MALDI-TOF mass spectrometry (MS) and 2) derivatization with 2-aminobenzamide followed by separation by high-performance liquid chromatography and analyses by MALDI-TOF MS, post source decay (PSD) MS, and MALDI-QoTOF MS/MS. The N-glycan profile of each developmental stage (Larva 1, Larva 2, Larva 3, Larva 4, and Dauer and adult) appears to be unique. The pattern of complex N-glycans was stage-specific with the general trend of number and abundance of glycans being Dauer approximately = L1 > adult approximately = L4 > L3 approximately = L2. Dauer larvae contained complex N-glycans with higher molecular masses than those seen in other stages. MALDI-QoTOF MS/MS of Hex4HexNAc4 showed an N-acetyllac-tosamine substitution not previously observed in C. elegans. Phosphorylcholine (Pc)-substituted glycans were also found to be stage-specific. Higher molecular weight Pc-containing glycans, including fucose-containing ones such as difucosyl Pc-glycan (Pc1dHex2Hex5HexNAc6) seen in Dauer larvae, have not been observed in any organism. Pc2Hex4HexNAc3, from Dauer larvae, when subjected to PSD MS analyses, showed Pc may substitute both core and terminally linked GlcNAc; no such structure has previously been reported in any organism. C. elegans-specific fucosyl and native methylated glycans were found in all developmental stages. Taken together, the above results demonstrate that in-depth investigation of the role of the above N-glycans during C. elegans development should lead to a better understanding of their significance and the ways that they may govern interactions, both within the organism during development and between the mobile nematode and its pathogens.     

LB1 and LB6 Homo floresiensis are not modern human (Homo sapiens) cretins

Excavations in the late Pleistocene deposits at Liang Bua cave, Flores, have uncovered the skeletal remains of several small-bodied and small-brained hominins in association with stone artefacts and the bones of Stegodon. Due to their combination of plesiomorphic, unique and derived traits, they were ascribed to a new species, Homo floresiensis, which, along with Stegodon, appears to have become extinct ∼17 ka (thousand years ago). However, recently it has been argued that several characteristics of H. floresiensis were consistent with dwarfism and evidence of delayed development in modern human (Homo sapiens) myxoedematous endemic (ME) cretins. This research compares the skeletal and dental morphology in H. floresiensis with the clinical and osteological indicators of cretinism, and the traits that have been argued to be associated with ME cretinism in LB1 and LB6. Contrary to published claims, morphological and statistical comparisons did not identify the distinctive skeletal and dental indicators of cretinism in LB1 or LB6 H. floresiensis. Brain mass, skeletal proportions, epiphyseal union, orofacial morphology, dental development, size of the pituitary fossa and development of the paranasal sinuses, vault bone thickness and dimensions of the hands and feet all distinguish H. floresiensis from modern humans with ME cretinism. The research team responsible for the diagnosis of ME cretinism had not examined the original H. floresiensis skeletal materials, and perhaps, as a result, their research confused taphonomic damage with evidence of disease, and thus contained critical errors of fact and interpretation. Behavioural scenarios attempting to explain the presence of cretinous H. sapiens in the Liang Bua Pleistocene deposits, but not unaffected H. sapiens, are both unnecessary and not supported by the available archaeological and geochronological evidence from Flores.     

Bundle sheath proteins are more sensitive to oxidative damage than those of the mesophyll in maize leaves exposed to paraquat or low temperatures

In maize leaves growth at low temperatures causes decreases in maximum catalytic activities of photosynthetic enzymes and reduced amounts of proteins, rather than effects on regulation or co-ordination of the photosynthetic processes. To test the hypothesis that differential localization of antioxidants between the different types of photosynthetic cell in maize leaves is a major determinant of the extreme sensitivity of maize leaves to chilling damage, oxidative damage to proteins, induced by incubation of maize leaves with paraquat, has been measured and compared with the effects incurred by growth at low temperatures. While the increase in protein carbonyl groups caused by paraquat treatment was much greater than that caused by low temperature growth conditions, most carbonyl groups were detected on bundle sheath proteins in both stress conditions. With one or two exceptions proteins located in the mesophyll tissues were free of protein carbonyl groups in both situations. Paraquat treatment caused a complete loss of the psaA gene products, modified the photosystem II reaction centre polypeptide, D1, and increased the number of peptides arising from breakdown of ribulose 1,5-bisphosphate carboxylase oxygenase (Rubisco). In contrast, growth at 15 degrees C increased the abundance (but not number) of Rubisco breakdown products and decreased that of the psaB gene product while the psaA gene product and PEP carboxylase were largely unaffected. Since bundle sheath proteins are more susceptible to oxidative damage than those located in the mesophyll cells, strategies for achieving a more balanced system of antioxidant defence may be effective in improving chilling tolerance in maize.     

Crystal structure of Homo sapiens kynureninase

Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.     

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.     

Tissue-specific synthesis of yolk proteins in Caenorhabditis elegans

The primary site of yolk protein synthesis in the nematode, Caenorhabditis elegans, has been determined. In animals containing no gonadal cells (obtained by laser ablation of the gonadal precursor cells early in development), yolk proteins are present in abundance. This demonstrates that yolk proteins are made outside the gonad. An examination of proteins present in tissues isolated by dissection, and a comparison of proteins synthesized by isolated tissues incubated in vitro have identified the intestine as the major site of yolk protein synthesis. We propose that yolk proteins are synthesized in the intestine, secreted from the intestine into the body cavity, and taken up from the body cavity by the gonad to reach oocytes. The site of yolk protein synthesis has also been examined in four mutants that have largely male somatic tissues, but a hermaphrodite germ line. Here again, yolk proteins are produced by intestines in a hermaphrodite-specific manner. This suggests that sex determination is coordinately regulated in intestinal and germ line tissues.     

Old World monkeys are more similar to humans than New World monkeys when playing a coordination game

There is much debate about how humans' decision-making compares with that of other primates. One way to explore this is to compare species' performance using identical methodologies in games with strategical interactions. We presented a computerized Assurance Game, which was either functionally simultaneous or sequential, to investigate how humans, rhesus monkeys and capuchin monkeys used information in decision-making. All species coordinated via sequential play on the payoff-dominant Nash equilibrium, indicating that information about the partner's choice improved decisions. Furthermore, some humans and rhesus monkeys found the payoff-dominant Nash equilibrium in the simultaneous game, even when it was the first condition presented. Thus, Old World primates solved the task without any external cues to their partner's choice. Finally, when not explicitly prohibited, humans spontaneously used language to coordinate on the payoff-dominant Nash equilibrium, indicating an alternative mechanism for converting a simultaneous move game into a sequential move game. This phylogenetic distribution implies that no single mechanism drives coordination decisions across the primates, while humans' ability to spontaneously use language to change the structure of the game emphasizes that multiple mechanisms may be used even within the same species. These results provide insight into the evolution of decision-making strategies across the primates.     

Accessible surfaces of beta proteins increase with increasing protein molecular mass more rapidly than those of other proteins

Here we present a systematic analysis of accessible surface areas and hydrogen bonds of 2554 globular proteins from four structural classes (all-α, all-β, α/β and α+β proteins) that is aimed to learn in which structural class the accessible surface area increases with increasing protein molecular mass more rapidly than in other classes, and what structural peculiarities are responsible for this effect. The beta structural class of proteins was found to be the leader, with the following possible explanations of this fact. First, in beta structural proteins, the fraction of residues not included in the regular secondary structure is the largest, and second, the accessible surface area of packaged elements of the beta-structure increases more rapidly with increasing molecular mass in comparison with the alpha-structure. Moreover, in the beta structure, the probability of formation of backbone hydrogen bonds is higher than that in the alpha helix for all residues of α+β proteins (the average probability is 0.73±0.01 for the beta-structure and 0.60±0.01 for the alpha-structure without proline) and α/β proteins, except for asparagine, aspartic acid, glycine, threonine, and serine (0.70±0.01 for the beta-structure and 0.60±0.01 for the alpha-structure without the proline residue). There is a linear relationship between the number of hydrogen bonds and the number of amino acid residues in the protein (Number of hydrogen bonds=0.678·number of residues-3.350).     

Caenorhabditis elegans has a single pathway to target matrix proteins to peroxisomes

All eukaryotes so far studied, including animals, plants, yeasts and trypanosomes, have two pathways to target proteins to peroxisomes. These two pathways are specific for the two types of peroxisome targeting signal (PTS) present on peroxisomal matrix proteins. Remarkably, the complete genome sequence of Caenorhabditis elegans lacks the genes encoding proteins specific for the PTS2 targeting pathway. Here we show, by expression of green fluorescent protein (GFP) reporters for both pathways, that the PTS2 pathway is indeed absent in C. elegans. Lack of this pathway in man causes severe disease due to mislocalization of PTS2-containing proteins. This raises the question as to how C. elegans has accommodated the absence of the PTS2 pathway. We found by in silico analysis that C. elegans orthologues of PTS2-containing proteins have acquired a PTS1. We propose that switching of targeting signals has allowed the PTS2 pathway to be lost in the phylogenetic lineage leading to C. elegans.     

Caenorhabditis elegans body wall muscles are simple actuators

Over the past four decades, one of the simplest nervous systems across the animal kingdom, that of the nematode worm Caenorhabditis elegans, has drawn increasing attention. This system is the subject of an intensive concerted effort to understand the behaviour of an entire living animal, from the bottom up and the top down. C. elegans locomotion, in particular, has been the subject of a number of models, but there is as yet no general agreement about the key (rhythm generating) elements. In this paper we investigate the role of one component of the locomotion subsystem, namely the body wall muscles, with a focus on the role of inter-muscular gap junctions. We construct a detailed electrophysiological model which suggests that these muscles function, to a first approximation, as mere actuators and have no obvious rhythm generating role. Furthermore, we show that within our model inter-muscular coupling is too weak to have a significant electrical effect. These results rule out muscles as key generators of locomotion, pointing instead to neural activity patterns. More specifically, the results imply that the reduced locomotion velocity observed in unc-9 mutants is likely to be due to reduced neuronal rather than inter-muscular coupling.