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Synthetic maps of human gene frequencies in Europeans.

Multivarate techniques can be used to condense the information for a large number of loci and alleles into one or a few synthetic variables. The geographic distribution of synthetic variables can be plotted by the same technique used in mapping the gene frequency of a single allele. Synthetic maps were constructed for Europe and the Near East, with the use of principal components to condense the information of 38 independent alleles from ten loci. The first principal component summarizes close to 30% of the total information and shows gradients. Maps thus constructed show clines in remarkable agreement with those expected on the basis of the spread of early farming in Europe, thus supporting the hypothesis that this spread was a demic spread rather than a cultural diffusion of farming technology.

Agriculture↗

Selection by consequences.

Selection by consequences is a causal mode found only in living things, or in machines made by living things. It was first recognized in natural selection, but it also accounts for the shaping and maintenance of the behavior of the individual and the evolution of cultures. In al three of these fields, it replaces explanations based on the causal modes of classical mechanics. The replacement is strongly resisted. Natural selection has now made its case, but similar delays in recognizing the role of selection in the other fields could deprive us of valuable help in solving the problems which confront us.

Behavior↗

PAK paradox: Paramecium appears to have more K(+)-channel genes than humans.

K(+)-selective ion channels (K(+) channels) have been found in bacteria, archaea, eucarya, and viruses. In Paramecium and other ciliates, K(+) currents play an essential role in cilia-based motility. We have retrieved and sequenced seven closely related Paramecium K(+)-channel gene (PAK) sequences by using previously reported fragments. An additional eight unique K(+)-channel sequences were retrieved from an indexed library recently used in a pilot genome sequencing project. Alignments of these protein translations indicate that while these 15 genes have diverged at different times, they all maintain many characteristics associated with just one subclass of metazoan K(+) channels (CNG/ERG type). Our results indicate that most of the genes are expressed, because all predicted frameshifts and several gaps in the homolog alignments contain Paramecium intron sequences deleted from reverse transcription-PCR products. Some of the variations in the 15 genomic nucleotide sequences involve an absence of introns, even between very closely related sequences, suggesting a potential occurrence of reverse transcription in the past. Extrapolation from the available genome sequence indicates that Paramecium harbors as many as several hundred of this one type of K(+)-channel gene. This quantity is far more numerous than those of K(+)-channel genes of all types known in any metazoan (e.g., approximately 80 in humans, approximately 30 in flies, and approximately 15 in Arabidopsis). In an effort to understand this plurality, we discuss several possible reasons for their maintenance, including variations in expression levels in response to changes in the freshwater environment, like that seen with other major plasma membrane proteins in Paramecium.

Alternative Splicing↗

Temperature-dependent utilization of meso-inositol: a useful biotyping marker in the genealogy of Salmonella typhimurium.

Salmonella typhimurium strains from natural sources either ferment or do not ferment meso-inositol in peptone water in 24 hr at 37 C. Ninety-five percent of the strains that are designated inositol-nonfermenting on the basis of their phenotype at 37 C ferment inositol when incubated at 25 C. Two classes of temperature-sensitive mutants were detected among the 712 strains of S. typhimurium examined. The occurrence of low-temperature fermentation of inositol among wild-type strains of S. typhimurium from biotypes 10 through 13 and FIRN suggested a genealogical relationship between these two groups, and that FIRN strains (fim(-)inl(ts)rha(-)) might have descended from ancestral types like biotype 10 through 13 strains (fim(+)inl(ts)rha(+)).

Biological Evolution↗

Diversity and origin of Desulfovibrio species: phylogenetic definition of a family.

The different nutritional properties of several Desulfovibrio desulfuricans strains suggest that either the strains are misclassified or there is a high degree of phenotypic diversity within the genus Desulfovibrio. The results of partial 16S rRNA and 23S rRNA sequence determinations demonstrated that Desulfovibrio desulfuricans ATCC 27774 and "Desulfovibrio multispirans" are closely related to the type strain (strain Essex 6) and that strains ATCC 7757, Norway 4, and El Agheila Z are not. Therefore, these latter three strains of Desulfovibrio desulfuricans are apparently misclassified. A comparative analysis of nearly complete 16S rRNA sequences in which we used a least-squares analysis method for evolutionary distances, an unweighted pair group method, a signature analysis method, and maximum parsimony was undertaken to further investigate the phylogeny of Desulfovibrio species. The species analyzed were resolved into two branches with origins deep within the delta subdivision of the purple photosynthetic bacteria. One branch contained five deep lineages, which were represented by (i) Desulfovibrio salexigens and Desulfovibrio desulfuricans El Agheila Z; (ii) Desulfovibrio africanus; (iii) Desulfovibrio desulfuricans ATCC 27774, Desulfomonas pigra, and Desulfovibrio vulgaris; (iv) Desulfovibrio gigas; and (v) Desulfomicrobium baculatus (Desulfovibrio baculatus) and Desulfovibrio desulfuricans Norway 4. A correlation between 16S rRNA sequence similarity and percentage of DNA relatedness showed that these five deep lineages are related at levels below the minimum genus level suggested by Johnson (in Bergey's Manual of Systematic Bacteriology, vol. 1, 1984). We propose that this branch should be grouped into a single family, the Desulfovibrionaceae. The other branch includes other genera of sulfate-reducing bacteria (e.g., Desulfobacter and Desulfococcus) and contains Desulfovibrio sapovorans and Desulfovibrio baarsii as separate, distantly related lineages.

Base Sequence↗

A novel domain in adenovirus L4-100K is required for stable binding and efficient inhibition of human granzyme B: possible interaction with a species-specific exosite.

Lymphocyte granule serine proteases (granzymes) play a critical role in protecting higher organisms against intracellular infections and cellular transformation. The proteases have also been implicated in the generation of tissue damage in a variety of chronic human conditions, including autoimmunity and transplant rejection. Granzyme B (GrB), one cytotoxic member of this family, achieves its effect through cleavage and activation of caspases as well as through caspase-independent proteolysis of cellular substrates. The 100,000-molecular-weight (100K) assembly protein of human adenovirus type 5 (Ad5-100K) was previously defined as a potent and specific inhibitor of human GrB. We now show that although human, mouse, and rat GrB proteases are well conserved in terms of structure, substrate specificity, and function, Ad5-100K inhibitory activity is directed exclusively against the human protease. Biochemical analysis demonstrates that the specificity of the 100K protein for human GrB resides in two distinct interactions with the protease: (i) a unique sequence within the reactive site loop (P(1))Asp(48)-(P(1'))Pro(49) in Ad5-100K which interacts with the active site and (ii) the presence of an additional inhibitor-enzyme interaction likely outside the enzyme catalytic site (i.e., an exosite). We have located this extended macromolecular interaction site in Ad5-100K within amino acids 688 to 781, and we have demonstrated that this region is essential for stable inhibitor-enzyme complex formation as well as efficient inhibition of human GrB. This novel component of the inhibitory mechanism of the 100K protein identifies a distinct target for selective inhibitor design, a finding which may be of benefit for diseases in which GrB plays a pathogenic role.

Adenoviruses, Human↗

The cultural heritage shapes the pattern of tumour profiles in Europe: a correlation study.

STUDY OBJECTIVE: This study investigates the spatial pattern of tumours in Europe to check the feasibility of a large scale ecological epidemiology approach to cancer in Europe. SETTING: The tumour types relative frequencies and cancer incidence (for men and women) reported in the European cancer registries were investigated by exploratory data analysis techniques. Socioeconomical descriptors of the female condition were considered as well. MAIN RESULTS: The classification of the European regional areas covered by the cancer registries followed almost exactly the boundaries set by the long and intermingled European history in terms of life styles and cultural heritage. This result supports the notion of a predominant role of environmental factors in cancer induction. Further support to the above result was given by the finding of a correlation between differential male-female cancer incidence, and socioeconomic descriptors of the female condition. CONCLUSIONS: From a methodological point of view, the consistency of these results pointed to the feasibility of an ecological approach to tumour epidemiology.

Cultural Diversity↗

Human gene therapy and slippery slope arguments.

Any suggestion of altering the genetic makeup of human beings through gene therapy is quite likely to provoke a response involving some reference to a 'slippery slope'. In this article the author examines the topography of two different types of slippery slope argument, the logical slippery slope and the rhetorical slippery slope argument. The logical form of the argument suggests that if we permit somatic cell gene therapy then we are committed to accepting germ line gene therapy in the future because there is no logically sustainable distinction between them. The rhetorical form posits that allowing somatic cell therapy now will be taking the first step on a slippery slope which will ultimately lead to the type of genocide perpetrated by the Nazis. The author tests the validity of these lines of argument against the facts of human gene therapy and concludes that because of their dependence on probabilities that cannot be empirically proven they should be largely disregarded in the much more important debate on moral line-drawing in gene therapy.

Advisory Committees↗

New frontiers in the future of aging: from successful aging of the young old to the dilemmas of the fourth age.

We review research findings on the oldest old that demonstrate that the fourth age entails a level of biocultural incompleteness, vulnerability and unpredictability that is distinct from the positive views of the third age (young old). The oldest old are at the limits of their functional capacity and science and social policy are constrained in terms of intervention. New theoretical and practical endeavors are required to deal with the challenges of increased numbers of the oldest old and the associated prevalence of frailty and forms of psychological mortality (e.g., loss of identity, psychological autonomy and a sense of control). Investigation of the fourth age is a new and challenging interdisciplinary research territory. Future study and discussion should focus on the critical question of whether the continuing major investments into extending the life span into the fourth age actually reduce the opportunities of an increasing number of people to live and die in dignity.

Aged↗

Agent-based computational economics: growing economies from the bottom up.

Agent-based computational economics (ACE) is the computational study of economies modeled as evolving systems of autonomous interacting agents. Thus, ACE is a specialization of economics of the basic complex adaptive systems paradigm. This study outlines the main objectives and defining characteristics of the ACE methodology and discusses similarities and distinctions between ACE and artificial life research. Eight ACE research areas are identified, and a number of publications in each area are highlighted for concrete illustration. Open questions and directions for future ACE research are also considered. The study concludes with a discussion of the potential benefits associated with ACE modeling, as well as some potential difficulties.

Computer Simulation↗

Precipitating factors of neurotic reactions in middle and upper-middle class Persian women (Iran).

In search of the socio-cultural factors contributing to the development of neurotic reactions in Persian women, the author has examined the records of two hundred and eighty five (285) patients from his private practice in Tehran. Factors to marital conflicts superceded the others by a wide margin. The content of marital conflicts seems to be related to the cultural confusion that has come out of the meeting of the cultural values of the West and the East. The author stresses the role of the communication media in the development of this confusion. In conclusion, implications and limitations of the paper were discussed.

Adult↗