August Weismann on Germ-Plasm Variation

August Weismann is famous for having argued against the inheritance of acquired characters. However, an analysis of his work indicates that Weismann always held that changes in external conditions, acting during development, were the necessary causes of variation in the hereditary material. For much of his career he held that acquired germ-plasm variation was inherited. An irony, which is in tension with much of the standard twentieth-century history of biology, thus exists – Weismann was not a Weismannian. I distinguish three claims regarding the germ-plasm: (1) its continuity,(2) its morphological sequestration, and (3) its variational sequestration. With respect to changes in Weismann's views on the cause of variation, I divide his career into four stages. For each stage I analyze his beliefs on the relative importance of changes in external conditions and sexual reproduction as causes ofvariation in the hereditary material. Weismann believed, and Weismannism denies, that variation, heredity, and development were deeply intertwined processes. This article is part of a larger project comparing commitments regarding variation during the latter half of the nineteenth century. This revised version was published online in July 2006 with corrections to the Cover Date.     

Rhizopogon spore bank communities within and among California pine forests

In this study we examine the distribution of Rhizopogon species in spore banks from five California pine forests. Four of the forest sites were discontinuous populations of Pinus muricata and a fifth was a Pinus ponderosa stand in Sierra National Forest. Rhizopogon species were retrieved by bioassaying the soils with pine seedlings followed by isolation of axenic cultures from individual root tips with typical Rhizopogon ectomycorrhizal morphology. The cultures were screened by ITS-RFLP and all unique patterns were sequenced. These sequences then were compared with those derived from identified sporocarp material. Bioassaying proved to be an efficient way to bring Rhizopogon species into culture. Approximately 50% of the pots contained ectomycorrhizal tips with Rhizopogon-like morphology, and axenic Rhizopogon cultures were obtained from half these pots. Our results showed that Rhizopogon spores usually are well distributed within local forest areas, while there is significant structuring of species at the regional scale. Spore longevity and homogenization by soil and water movement might explain their distribution within local forest areas, while the regional pattern might be explained by limited long distance dispersal or climatic and edaphic differences.     

Linkage disequilibrium and inference of ancestral recombination in 538 single-nucleotide polymorphism clusters across the human genome

The prospect of using linkage disequilibrium (LD) for fine-scale mapping in humans has attracted considerable attention, and, during the validation of a set of single-nucleotide polymorphisms (SNPs) for linkage analysis, a set of data for 4,833 SNPs in 538 clusters was produced that provides a rich picture of local attributes of LD across the genome. LD estimates may be biased depending on the means by which SNPs are first identified, and a particular problem of ascertainment bias arises when SNPs identified in small heterogeneous panels are subsequently typed in larger population samples. Understanding and correcting ascertainment bias is essential for a useful quantitative assessment of the landscape of LD across the human genome. Heterogeneity in the population recombination rate, rho=4Nr, along the genome reflects how variable the density of markers will have to be for optimal coverage. We find that ascertainment-corrected rho varies along the genome by more than two orders of magnitude, implying great differences in the recombinational history of different portions of our genome. The distribution of rho is unimodal, and we show that this is compatible with a wide range of mixtures of hotspots in a background of variable recombination rate. Although rho is significantly correlated across the three population samples, some regions of the genome exhibit population-specific spikes or troughs in rho that are too large to be explained by sampling. This result is consistent with differences in the genealogical depth of local genomic regions, a finding that has direct bearing on the design and utility of LD mapping and on the National Institutes of Health HapMap project.     

Population coding in somatosensory cortex

Computational analyses have begun to elucidate which components of somatosensory cortical population activity may encode basic stimulus features. Recent results from rat barrel cortex suggest that the essence of this code is not synergistic spike patterns, but rather the precise timing of single neuron's first post-stimulus spikes. This may form the basis for a fast, robust population code.     

Dynamic localization of proteins and DNA during a bacterial cell cycle

A cellular differentiation programme that culminates in an asymmetric cell division is an integral part of the cell cycle in the bacterium Caulobacter crescentus. Recent work has uncovered mechanisms that ensure the execution of many events at different times during the cell cycle and at specific places in the cell. Surprisingly, in this one-micron bacterial cell, the dynamic spatial disposition of regulatory proteins, structural proteins and specific regions of the chromosome are important components of both cell-cycle progression and the generation of daughter cells with different cell fates.     

A critical assessment of different measures of the information carried by correlated neuronal firing

Information theoretic measures have been proposed as a quantitative framework to clarify the role of correlated neuronal activity in the brain. In this paper we review some recent methods that allow precise assessments of the role of correlation in stimulus coding and decoding by the nervous system. We present new results that make explicit links between types of encoding and decoding mechanisms based on correlations. We illustrate the concepts by showing that the spike trains of pairs of neurons in rat somatosensory cortex can be decoded almost perfectly without including knowledge of correlation in the read-out model, although in this neural system correlations between spike times contribute appreciably to stimulus encoding.     

Enhanced B-Cell Receptor Recognition of the Autoantigen Transglutaminase 2 by Efficient Catalytic Self-Multimerization

A hallmark of the gluten-driven enteropathy celiac disease is autoantibody production towards the enzyme transglutaminase 2 (TG2) that catalyzes the formation of covalent protein-protein cross-links. Activation of TG2-specific B cells likely involves gluten-specific CD4 T cells as production of the antibodies is dependent on disease-associated HLA-DQ allotypes and dietary intake of gluten. IgA plasma cells producing TG2 antibodies with few mutations are abundant in the celiac gut lesion. These plasma cells and serum antibodies to TG2 drop rapidly after initiation of a gluten-free diet, suggestive of extrafollicular responses or germinal center reactions of short duration. High antigen avidity is known to promote such responses, and is also important for breakage of self-tolerance. We here inquired whether TG2 avidity could be a feature relevant to celiac disease. Using recombinant enzyme we show by dynamic light scattering and gel electrophoresis that TG2 efficiently utilizes itself as a substrate due to conformation-dependent homotypic association, which involves the C-terminal domains of the enzyme. This leads to the formation of covalently linked TG2 multimers. The presence of exogenous substrate such as gluten peptide does not inhibit TG2 self-cross-linking, but rather results in formation of TG2-TG2-gluten complexes. The celiac disease autoantibody epitopes, clustered in the N-terminal part of TG2, are conserved in the TG2-multimers as determined by mass spectrometry and immunoprecipitation analysis. TG2 multimers are superior to TG2 monomer in activating A20 B cells transduced with TG2-specific B-cell receptor, and uptake of TG2-TG2-gluten multimers leads to efficient activation of gluten-specific T cells. Efficient catalytic self-multimerization of TG2 and generation of multivalent TG2 antigen decorated with gluten peptides suggest a mechanism by which self-reactive B cells are activated to give abundant numbers of plasma cells in celiac disease. Importantly, high avidity of the antigen could explain why TG2-specific plasma cells show signs of an extrafollicular generation pathway.     

Natural transformation of <Emphasis Type="Italic">Vibrio cholerae</Emphasis> as a tool - Optimizing the procedure

Background  

Vibrio cholerae gains natural competence upon growth on chitin. This allows the organism to take up free DNA from the environment and to incorporate it into its genome by homologous recombination.