Microorganisms seen by scanning and transmission electron microscopy in Legionnaires' disease from human lung

Summary In addition to several anomalous structures, other general forms of definitely rod-shaped microorganisms have been found by scanning and transmission electron microscopy in the lung tissue taken at autopsy from a patient who succumbed to confirmed Legionnaires' disease with extensive necrotizing lobar pneumonia. The microorganisms were greatly varied in size and shape. They were micrographed in the act of fission. These forms have been found to some extent throughout the tissue. No nickel was demonstrated, either in the lung tissue or in the microorganisms.This work has been supported in part by a Henry Ford Hospital institutional grant from the Ford Foundation and in part by the Veterans Administration Medical Center Research Funds.     

Becoming a Darwinian: the micro-politics of Sir Francis Galton's scientific career 1859-65

In 1865 Francis Galton (1822-1911) published 'Hereditary Talent and Character', an elaborate attempt to prove the heritability of intelligence on the basis of pedigree data. It was the start of Galton's lifelong commitment to investigating the statistical patterns and physiological mechanisms of hereditary transmission. Most existing attempts to explain Galton's fascination for heredity have argued that he was driven by a commitment to conservative political ideologies to seek means of naturalizing human inequality. However, this paper shows that another factor of at least equal importance has been overlooked by Galton scholars: his determination during the 1860s to be accepted among the ranks of the Darwinian inner circle. By hitching his career to the fortunes of what looked likely to emerge as a new scientific elite, Galton felt that he could bypass the typically slow and uncertain route to achieving scientific distinction. For this essentially strategic reason, between 1860 and 1865 he drifted away from a set of existing scientific concerns that were failing to deliver the approbation that he desired. Earnestly seeking to ingratiate himself with the Darwinian lobby, he then toyed with a variety of potential research projects relevant to Darwinian evolution. Yet Galton consistently failed to stimulate the enthusiasm of the Darwinians. Finally, however, after several months of ruminating, in 1864 he settled on a study of eminent pedigrees as a subject that was both germane and highly useful to the Darwinian enterprise. Galton's willingness to shift the direction of his scientific career during the 1860s underscores the importance of examining the micro-politics of scientific careers in addition to their broader social and political context. This account also emphasizes the limitations of class-based explanations even when considering scientists whose work seems so manifestly indicative of ideological motivation.     

Einstein’s Investigations of Galilean Covariant Electrodynamics Prior to 1905

Einstein learned from the magnet and conductor thought experiment how to use field transformation laws to extend the covariance of Maxwells electrodynamics. If he persisted in his use of this device, he would have found that the theory cleaves into two Galilean covariant parts, each with different field transformation laws. The tension between the two parts reflects a failure not mentioned by Einstein: that the relativity of motion manifested by observables in the magnet and conductor thought experiment does not extend to all observables in electrodynamics. An examination of Ritzs work shows that Einsteins early view could not have coincided with Ritzs on an emission theory of light, but only with that of a conveniently reconstructed Ritz. One Ritz-like emission theory, attributed by Pauli to Ritz, proves to be a natural extension of the Galilean covariant part of Maxwells theory that happens also to accommodate the magnet and conductor thought experiment. Einsteins famous chasing a light beam thought experiment fails as an objection to an ether-based, electrodynamical theory of light. However it would allow Einstein to formulate his general objections to all emission theories of light in a very sharp form. Einstein found two well known experimental results of 18th and 19th century optics compelling (Fizeaus experiment, stellar aberration), while the accomplished Michelson-Morley experiment played no memorable role. I suggest they owe their importance to their providing a direct experimental grounding for Lorentz local time, the precursor of Einsteins relativity of simultaneity, and doing it essentially independently of electrodynamical theory. I attribute Einsteins success to his determination to implement a principle of relativity in electrodynamics, but I urge that we not invest this stubbornness with any mystical prescience.I am grateful to Diana Buchwald, Olivier Darrigol, Allen Janis, Michel Janssen, Robert Rynasiewicz and John Stachel for helpful discussion and for assistance in accessing source materials.     

Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid

Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae).     

Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer

The identification of tumor-suppressor genes in solid tumors by classical cancer genetics methods is difficult and slow. We combined nonsense-mediated RNA decay microarrays and array-based comparative genomic hybridization for the genome-wide identification of genes with biallelic inactivation involving nonsense mutations and loss of the wild-type allele. This approach enabled us to identify previously unknown mutations in the receptor tyrosine kinase gene EPHB2. The DU 145 prostate cancer cell line, originating from a brain metastasis, carries a truncating mutation of EPHB2 and a deletion of the remaining allele. Additional frameshift, splice site, missense and nonsense mutations are present in clinical prostate cancer samples. Transfection of DU 145 cells, which lack functional EphB2, with wild-type EPHB2 suppresses clonogenic growth. Taken together with studies indicating that EphB2 may have an essential role in cell migration and maintenance of normal tissue architecture, our findings suggest that mutational inactivation of EPHB2 may be important in the progression and metastasis of prostate cancer.     

Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase cause childhood-onset severe retinal dystrophy

We identified three consanguineous Austrian kindreds with 15 members affected by autosomal recessive childhood-onset severe retinal dystrophy, a genetically heterogeneous group of disorders characterized by degeneration of the photoreceptor cells. A whole-genome scan by microarray analysis of single-nucleotide polymorphisms (ref. 2) identified a founder haplotype and defined a critical interval of 1.53 cM on chromosome 14q23.3-q24.1 that contains the gene associated with this form of retinal dystrophy. RDH12 maps in this region and encodes a retinol dehydrogenase proposed to function in the visual cycle. A homozygous 677A-->G transition (resulting in Y226C) in RDH12 was present in all affected family members studied, as well as in two Austrian individuals with sporadic retinal dystrophy. We identified additional mutations in RDH12 in 3 of 89 non-Austrian individuals with retinal dystrophy: a 5-nucleotide deletion (806delCCCTG) and the transition 565C-->T (resulting in Q189X), each in the homozygous state, and 146C-->T (resulting in T49M) and 184C-->T (resulting in R62X) in compound heterozygosity. When expressed in COS-7 cells, Cys226 and Met49 variants had diminished and aberrant activity, respectively, in interconverting isomers of retinol and retinal. The severe visual impairment of individuals with mutations in RDH12 is in marked contrast to the mild visual deficiency in individuals with fundus albipunctatus caused by mutations in RDH5, encoding another retinal dehydrogenase. Our studies show that RDH12 is associated with retinal dystrophy and encodes an enzyme with a unique, nonredundant role in the photoreceptor cells.