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Late Pleistocene human population bottlenecks, volcanic winter, and differentiation of modern humans.

The "Weak Garden of Eden" model for the origin and dispersal of modern humans (Harpending et al., 1993) posits that modern humans spread into separate regions from a restricted source, around 100 ka (thousand years ago), then passed through population bottlenecks. Around 50 ka, dramatic growth occurred within dispersed populations that were genetically isolated from each other. Population growth began earliest in Africa and later in Eurasia and is hypothesized to have been caused by the invention and spread of a more efficient Later Stone Age/Upper Paleolithic technology, which developed in equatorial Africa. Climatic and geological evidence suggest an alternative hypothesis for Late Pleistocene population bottlenecks and releases. The last glacial period was preceded by one thousand years of the coldest temperatures of the Later Pleistocene (approximately 71-70 ka), apparently caused by the eruption of Toba, Sumatra. Toba was the largest known explosive eruption of the Quaternary. Toba's volcanic winter could have decimated most modern human populations, especially outside of isolated tropical refugia. Release from the bottleneck could have occurred either at the end of this hypercold phase, or 10,000 years later, at the transition from cold oxygen isotope stage 4 to warmer stage 3. The largest populations surviving through the bottleneck should have been found in the largest tropical refugia, and thus in equatorial Africa. High genetic diversity in modern Africans may thus reflect a less severe bottleneck rather than earlier population growth. Volcanic winter may have reduced populations to levels low enough for founder effects, genetic drift and local adaptations to produce rapid population differentiation. If Toba caused the bottlenecks, then modern human races may have differentiated abruptly, only 70 thousand years ago.

Animals↗

High copy display of large proteins on phage for functional selections.

We have isolated mutations in the major coat protein P8 of M13 phage that greatly increase the surface display of monomeric or oligomeric proteins. The monomeric protein, human growth hormone (hGH), was fused to the N terminus of P8; libraries of P8 variants were constructed and variants that increased hGH display were selected by binding to the extracellular domain of the hGH receptor. The hGH-P8 fusion protein was found to be extremely tolerant of mutations, and a number of P8 variants were found that increased display to levels that improved detection of the hGH-P8 fusion by almost 100-fold. The increased display likely results from better accommodation of the hGH-P8 fusion protein in the phage coat. Using this high copy display format, it was possible for the first time to detect variants of hGH with very weak affinities for the hGHbp (K(d)>1 microM). The display of a tetrameric protein, streptavidin (approximately 50 kDa), was also increased, suggesting the approach may be general to many proteins. The initial product of a natural or invented selection from a naive library is often a weakly functioning protein. These improvements in high copy display should facilitate the broader goal for selection of proteins with novel functions.

Amino Acid Sequence↗

Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains.

Central cellular functions such as metabolism, solute transport and signal transduction are regulated, in part, via binding of small molecules by specialized domains. Using sensitive methods for sequence profile analysis and protein structure comparison, we exhaustively surveyed the protein sets from completely sequenced genomes for all occurrences of 21 intracellular small-molecule-binding domains (SMBDs) that are represented in at least two of the three major divisions of life (bacteria, archaea and eukaryotes). These included previously characterized domains such as PAS, GAF, ACT and ferredoxins, as well as three newly predicted SMBDs, namely the 4-vinyl reductase (4VR) domain, the NIFX domain and the 3-histidines (3H) domain. Although there are only a limited number of different superfamilies of these ancient SMBDs, they are present in numerous distinct proteins combined with various enzymatic, transport and signal-transducing domains. Most of the SMBDs show considerable evolutionary mobility and are involved in the generation of many lineage-specific domain architectures. Frequent re-invention of analogous architectures involving functionally related, but not homologous, domains was detected, such as, fusion of different SMBDs to several types of DNA-binding domains to form diverse transcription regulators in prokaryotes and eukaryotes. This is suggestive of similar selective forces affecting the diverse SMBDs and resulting in the formation of multidomain proteins that fit a limited number of functional stereotypes. Using the "guilt by association approach", the identification of SMBDs allowed prediction of functions and mode of regulation for a variety of previously uncharacterized proteins.

Amino Acid Sequence↗

Domain combinations in archaeal, eubacterial and eukaryotic proteomes.

There is a limited repertoire of domain families that are duplicated and combined in different ways to form the set of proteins in a genome. Proteins are gene products, and at the level of genes, duplication, recombination, fusion and fission are the processes that produce new genes. We attempt to gain an overview of these processes by studying the evolutionary units in proteins, domains, in the protein sequences of 40 genomes. The domain and superfamily definitions in the Structural Classification of Proteins Database are used, so that we can view all pairs of adjacent domains in genome sequences in terms of their superfamily combinations. We find 783 out of the 859 superfamilies in SCOP in these genomes, and the 783 families occur in 1307 pairwise combinations. Most families are observed in combination with one or two other families, while a few families are very versatile in their combinatorial behaviour; 209 families do not make combinations with other families. This type of pattern can be described as a scale-free network. We also study the N to C-terminal orientation of domain pairs and domain repeats. The phylogenetic distribution of domain combinations is surveyed, to establish the extent of common and kingdom-specific combinations. Of the kingdom-specific combinations, significantly more combinations consist of families present in all three kingdoms than of families present in one or two kingdoms. Hence, we are led to conclude that recombination between common families, as compared to the invention of new families and recombination among these, has also been a major contribution to the evolution of kingdom-specific and species-specific functions in organisms in all three kingdoms. Finally, we compare the set of the domain combinations in the genomes to those in the RCSB Protein Data Bank, and discuss the implications for structural genomics.

Animals↗

Longitudinally detected EPR: improved instrumentation and new pulse schemes.

A new setup for longitudinal detection (LOD) of EPR signals based on a commercial pulse EPR spectrometer equipped with an ENDOR probehead is presented. The design is suited for pulse LOD EPR and amplitude-modulated cw LOD EPR experiments. The sensitivity is substantially increased compared with earlier designs. Two new pulse schemes that take full advantage of the special properties of the setup are invented. In transient-nutation longitudinally detected EPR (TN-LOD EPR), the nutation of magnetization during a microwave pulse is used to measure the EPR signal. In pulse-train excited longitudinally detected EPR (PT-LOD EPR), a train of microwave pulses that periodically inverts the magnetization is applied. First experimental results on radicals and metal complexes at room temperature are presented.

Journal Article↗

"Living" under the challenge of information decay: the stochastic corrector model vs. hypercycles.

The combined problem of having a large genome size when the accuracy of replication was a limiting factor is probably the most difficult transition to explain at the late stages of RNA world. One solution has been to suggest the existence of a cyclically coupled system of autocatalytic and cross-catalytic molecular mutualists, where each member helps the following member and receives help from the preceding one (i.e., a "hypercycle"). However, such a system is evolutionarily unstable when mutations are taken into account because it lacks individuality. In time, the cooperating networks of genes should have been encapsulated in a cell-like structure. But once the cell was invented, it closely aligned genes' common interests and helped to reduce gene selfishness, so there was no need for hypercycles. A simple package of competing genes, described by the "stochastic corrector model" (SCM), could have provided the solution. Until now, there is no clear demonstration that the proposed mechanisms (compartmentalized hypercycles and the stochastic corrector model) do in fact solve the error threshold problem. Here, we present a Monte Carlo model to test the viability of protocell populations that enclose a hypercyclic (HPC) or a non-hypercyclic (SCM) system when faced with realistic mutation rates before the evolution of efficient enzymic machinery for replication. The numerical results indicate that both systems are efficient information integrators and are able to overcome the danger of information decay in the absence of accurate replication. However, a population of SCM protocells can tolerate higher deleterious mutation rates and reaches an equilibrium mutational load lower than that in a population of HPC protocells.

Animals↗

Antibody-Defined Epitope Mapping Using the Multipin Method of Peptide Synthesis

The multipin method for peptide synthesis was developed for antibody epitope mapping. From its initial invention as a method for testing many short peptides on the solid surface used for their synthesis, it has evolved into a method for producing solutions of peptides of a wide range of lengths in many "formats," such as tagged (biotinylated) peptides for binding studies or affinity chromatography. The power of the multipin technique lies in the large number and variety of peptides that can be rapidly made and efficiently tested.

Journal Article↗

The mitochondrial cytochrome oxidase II gene in Bacillus stick insects: ancestry of hybrids, androgenesis, and phylogenetic relationships.

Sequencing of a cytochrome oxidase II (COII) gene fragment in Bacillus taxa provided evidence that the bisexual B. rossius is the maternal ancestor of the hybridogenetic B. rossius-grandii strains and revealed the same ancestry for both parthenogenetic hybrids: the diploid B. whitei (B. rossius/grandii grandii) and the triploid B. lynceorum (B. rossius/grandii grandii/atticus). Present data clearly demonstrate that all Bacillus unisexuals arose through asymmetrical hybridization events and realized a paraphyletic derivation from the B. rossius redtenbacheri subspecies. The invention of B. rossius mitochondrial DNA haplotypes in specimens with B. grandii grandii nuclear genomes revealed the occurrence of androgenesis in nature. Natural androgens represent a peculiar escape from hybridity and can help maintain the hybridogenetic system through the production of the fathering taxon via hybrid females. Results from the COII gene support the phyletic relationships among taxa suggested by previous taxonomical approaches, but also indicate a departure of B. grandii subspecies from the established taxonomy. Assuming the existence of a molecular clock, the evaluated substitution rate brings the splitting between B. rossius and B. grandii/B. atticus back to 22.79 +/- 2.65 myr before present, while the origin of hybrids appears to be much more recent (1.06 +/- 0.53 myr).

Androgens↗

The rise and fall of great class I genes.

Class I major histocompatibility complex molecules are components of the vertebrate immune system. Polymorphic classical class I molecules determine the specificity of cytolytic T cell and natural killer cell responses and are found in all species. During the timeframe of mammalian evolution, the lifetimes of a functional class I locus are short and those of individual alleles even shorter. In this seminar the role of heterozygote advantage frequency-dependent selection, disease-specific selection and drift in driving this rapid evolution is discussed. The other, non-classical genes, perform other functions within the immune system. They are of more recent invention than the classical class I genes and appear to have evolved from classical class I alleles.

Antigen Presentation↗

Evolution of the Archaea.

Archaea, members of the third domain of life, are bacterial-looking prokaryotes that harbour many unique genotypic and phenotypic properties, testifying for their peculiar evolutionary status. The archaeal ancestor was probably a hyperthermophilic anaerobe. Two archaeal phyla are presently recognized, the Euryarchaeota and the Crenarchaeota. Methanogenesis was the main invention that occurred in the euryarchaeal phylum and is now shared by several archaeal groups. Adaptation to aerobic conditions occurred several times independently in both Euryarchaeota and Crenarchaeota. Recently, many new groups of Archaea that have not yet been cultured have been detected by PCR amplification of 16S ribosomal RNA from environmental samples. The phenotypic and genotypic characterization of these new groups is now a top priority for further studies on archaeal evolution.

Archaea↗

A quest for cytoplasmic factors that control the cell cycle.

Between 1966 and 1986 the author and his former students carried out an investigation into the cytoplasmic factors that regulate nuclear behaviour during meiotic maturation of oocytes. This anecdotal chronicle traces the development of the problems and the direction in which their solutions were attempted in the course of this investigation. The author examines why he decided to study oocyte maturation, how he discovered progesterone as a maturation-inducing hormone and maturation promoting factor (MPF) and cytostatic factor (CSF) as meiosis-controlling factors, how the idea of the cell cycle without the cell occurred to him, and how it was materialised by invention of a cell-free system.

Animals↗

Nucleic acid based sensors.

Nucleic acids may be analyte or molecular recognition elements in biosensors. Both aspects merge in the genosensor approach, where detection of special sequences is facilitated by hybridization of a target nucleic acid to a complementary immobilized template. All three roles of nucleic acids in biosensors are discussed and the state of sensor development reviewed. With the invention of evolutionary synthesis strategies applied to nucleic acids new types of biomolecular receptors are accessible. The impact of aptamers and ribozymes on biosensor development is discussed.

Adsorption↗

The history of pediatric surgery in France.

In 1741, Nicolas Andry, counsellor of King Louis XV, published a book about "orthopedics," inventing this word. The book is interesting as the author refers to beliefs and habits of the time. In 1864, Guersant published Notes About Pediatric Surgery, a real textbook which was translated into English and German and dealt with the importance of children's psychological training, anesthesia, and water or mother's milk after the operation, and also described tracheotomy, draining of cervical adenitis, and lithotrity. The classification of bone affections was still very confused. Tuberculosis and syphilis have an important place; hypospadias is not treated by surgery. In 1905, Froehlich published Pediatric Surgery Studies dealing exclusively with visceral surgery and demonstrating progress compared to Guersant's study. In 1906, Kirmisson published Pediatric Surgical Textbook, containing the first discussion of radiology and the description of the pathology of the omphalomesenteric duct and of other congenital malformations. Osteomyelitis was given its proper name, and cervical fistulas were explained. In 1914, A. Broca achieved further progress describing treatments of megacolon, intussusception, and the operation of Fredet Ramstedt. The book by Ombredanne, already out of date at the time of its publication, showed that he was not aware of the wartime, progress achieved by Ladd and Gross in the USA. French publications have diminished since then, and French pediatric surgery is still trying to find a precise identity.

France↗

Denis Browne: surgeon.

Denis Browne was the first surgeon in England to confine his practice entirely to children. The methods of treatment devised by him were new and often revolutionary and were frequently attacked and criticized, but they worked. He regarded his research into the aetiology of congenital deformities as his most important single scientific contribution. In 1931, he published his first article on talipes equinovarus. He further enlarged his theory of the mechanical origin of congenital deformities in a study published in 1936. The mechanical theory led him to search for treatment by use of selectively applied pressures and controlled movements. He did not like open corrections. When confronted by a surgical problem he would invariably start by studying the anatomy of the region involved. He was the first to describe the superficial inguinal pouch. His anatomical studies eventually enabled him to perfect the operation for inguinal hernia in infancy and childhood and formed the basis of his operation for cleft palate and of his work on the surgical anatomy of the tonsil. He was the first pediatric surgeon to routinely employ transverse abdominal incisions. He preferred immediate anastomosis to the temporary enterostomies. He introduced the end-to-back anastomosis. He helped rationalizing and perfecting the operative technique for pyloric stenosis. Malformations of the perineum were the subject of many studies. His operation for hypospadias is also well known. His other advances in paediatric surgery, such as treatment of various infective conditions and cardiovascular surgery, were at the time original and important. His inventive genius was best seen in his development of numerous instruments and appliances.(ABSTRACT TRUNCATED AT 250 WORDS)

England↗

Trends and challenges in enzyme technology.

Several major developments took place in the field of biocatalysis over the past few years. These include the invention of directed evolution as an extremely useful method for biocatalyst improvement on the molecular level in combination with high-throughput screening systems, methods for accessing "nonculturable" biodiversity using metagenome approaches and progress in sequence-based biocatalyst discovery. In addition, new carriers and tools for immobilization of enzymes have been developed. For the synthesis of optically active compounds impressive examples using new enzymes and major progress in dynamic kinetic resolutions of racemates took place. These achievements are summarized in this review.

Biotechnology↗

Ethnocentricity and the social construction of 'mass hysteria'.

This study provides a critical historical review and analysis of the variety of human expressions which have been erroneously labeled under the grandiose category "mass hysteria". It is argued that Western science reductionist approaches to the classification of "mass hysteria" treat it as an entity to be discovered transculturally, and in their self-fulfilling search for universals systematically exclude what does not fit within the autonomous parameters of its Western-biased culture model, exemplifying what Kleinman (1977) terms a "category fallacy." As a result of objectivist methodologies, the etiology of actions labeled as "mass hysteria" is typically viewed as deviant, irrational or abnormal behavior resulting from a malfunctioning 'proper' social order. However, what constitutes 'the' correct social order is a function of a researcher's historical sociocultural and/or scientific milieu. This study reviews the problem, advocating Geertz's (1973) culturally relativistic approach to understanding various cross-cultural behavior that is sensitive to and tolerant of the unique context and milieu of participants. "Mass" or "epidemic hysteria" is viewed as an invention of Western psychiatry and should be abandoned and replaced with the term collective exaggerated emotions. Instead of attempting to 'discover' a neatly packaged, unitary external disease entity, the focus of a meaning-oriented approach emphasizes the deciphering of foreign realities, semantic networks and symbol systems.

Anthropology, Cultural↗

A case for sharing.

Unlike in other branches of science and technology, computer programs and algorithms are generally not fully disclosed. This leads to duplication of effort, and prevents building new knowledge rapidly on existing knowledge. To remedy this, effective patents on computer programs and algorithms should be granted. The community of authors and inventors, along with expert advice from patent attorneys, have to arrive at effective and equitable definitions of obviousness and novelty, so that the boundaries of protection on one side, and free progress on the other, can be defined. The same reasons exist for patenting and disclosing computer software knowledge as for chemistry, electrical and mechanical inventions. Patenting has protected inventors and assured progress for many decades successfully in these fields.

Documentation↗

Christoph Scheiner's eye studies.

Christoph Scheiner was born in 1573 or 1575. In 1595 he entered into the Order of the Jesuits; he died in 1650. In 1619 his book Oculus, dealing with the optics of the eye, appeared in Innsbruck. The invention of the telescope was of utmost importance for progress in astronomical and physical research. Scheiner himself built telescopes and discovered the sunspots. As a result, an unpleasant priority dispute with Galilei ensued. From 1624 onwards, Scheiner was in Rome, where his main work Rosa Ursina was published in 1630. A part of this book deals with the physiological optics of the eye as well. Some of his discoveries and experiments are taken from these two books: determination of the radius of curvature of the cornea, discovery of the nasal exit of the optic nerve, increase in the radius of curvature of the lens in case of accommodation, Scheiner's procedure (double images with ametropia), refractive indices of various parts of the eye, Scheiner's experiment. Without any doubt, Christoph Scheiner belongs to the foremost scientists of the first half of the 17th century.

Germany↗