Einstein＇s Third Paradise

Historians of moden science have good reasons to be grateful to Paul Arthur Schilpp, professor of philosophy and Methodist clergyman but better known as the editor of a series of volumes on “Living Philosophers,” including several on scientist - philosophers. His motto was:“The asking of questions about a philosopher‘s meaning while he is alive.” And to his everlasting credit,     

Constitutional 11p15 abnormalities, including heritable imprinting center mutations, cause nonsyndromic Wilms tumor

Constitutional abnormalities at the imprinted 11p15 growth regulatory region cause syndromes characterized by disordered growth, some of which include a risk of Wilms tumor. We explored their possible contribution to nonsyndromic Wilms tumor and identified constitutional 11p15 abnormalities in genomic lymphocyte DNA from 13 of 437 individuals (3%) with sporadic Wilms tumor without features of growth disorders, including 12% of bilateral cases (P = 0.001) and in one familial Wilms tumor pedigree. No abnormality was detected in 220 controls (P = 0.006). Abnormalities identified included H19 DMR epimutations, uniparental disomy 11p15 and H19 DMR imprinting center mutations (one microinsertion and one microdeletion), thus identifying microinsertion as a new class of imprinting center mutation. Our data identify constitutional 11p15 defects as one of the most common known causes of Wilms tumor, provide mechanistic insights into imprinting disruption and reveal clinically important epigenotype-phenotype associations. The impact on clinical management dictates that constitutional 11p15 analysis should be considered in all individuals with Wilms tumor.     

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.     

Effects of habitat fragmentation and differing mobility on the population structures of a Great Basin dragonfly ( Sympetrum corruptum ) and damselfly ( Enallagma carunculatum )

The population structure of 2 Great Basin odonate species was assessed using protein electrophoresis. Analyses included 7 populations of Sympetrum corruptum (suborder Anisoptera), a migratory and highly mobile dragonfly, and 8 populations of Enallagma carunculatum (suborder Zygoptera), a weak flier that is not known to migrate far from natal water sources. Though we expected the damselfly ( E. carunculatum ) to show greater genetic isolation than the dragonfly ( S. corruptum ), both species apparently had high levels of gene flow (theta = 0.0604 for S. corruptum , theta = 0.0485 for E. carunculatum ) and showed no evidence for isolation by distance. These results suggest that both species are highly vagile and that the most important factors affecting population structure of these odonates may be ecological conditions such as habitat patchiness and the ephemerality of water sources.     

What distinguishes cosmopolitan and endemicDrosophila species?

Summary CosmopolitanDrosophila species can survive wide ecological tolerances measured by resistance to desiccation/temperature extremes compared with endemic rain forest species. This, rather than any genetic features, is important in helping to explain the widespread distributions of cosmopolitan species.We thank Dr Lee Ehrman for cultures ofD. paulistorum, and the Australian Research Grants Committee for financial support.     

Suppression of immunization to tuberculosis and diphtheria by an extract of lymphoid tissue

Zusammenfassung Dank einer neuen Anwendung von Lymphknotenextrakten (statt Röntgenextrakten, Corticosteroiden, Antilymphozytenserum usw.) wird eine erhebliche Reduktion der immunologischen Reaktion erzielt, wenn die Tiere mit diesen Extrakten vorbehandelt und gleichzeitig mit Antigenen behandelt werden.

---

---

This investigation was supported in part by U.S.P.H.S. Research Grant No. CA-02624 from National Cancer Institute; and in part by an institutional grant to Detroit Institute of Cancer Research from United Foundation of greater Detroit allocated through Michigan Cancer Foundation and the Detroit General Hospital Research Corporation, and Newaygo County Cancer Society.     

The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria

Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis.     

A histochemical study of immune destruction of the lymphopoietic system

Zusammenfassung Eine auffallende Zunahme von -Galactosidase kommt im lymphoetischen Säuger-Gewebe im Zusammenhang mit der immunologischen Auflösung dieses Systems vor. Die hernach auftretende Proliferation retikulärer Zellen steht im Zusammenhang mit der Regeneration dieses Organs. Diese Zellen enthalten eine reichliche Anzahl lysosomatischer Enzyme (z.B. -Galactosidase).

---

---

This investigation was supported in part by Public Health Service Research Grants Nos. Ca 02624 and CA 02903 from the National Cancer Institute and in part by an institutional grant to the Detroit Institute of Cancer Research Division of the Michigan Cancer Foundation from the United Foundation of Greater Detroit, and Detroit General Hospital Research Corporation. Newaygo County Cancer Association. We wish to express our gratitude for stenographic assistance to Mrs.Connie Malucusky and MissPatricia Warzocha.     

A potent non-steroidal anti-inflammatory agent: 2-[3-chloro-4(3-pyrrolinyl)phenyl]propionic acid

Zusammenfassung Die Synthese und biologische Prüfung von 2-[3-Chlor-4(3-pyrrolinyl)phenyl]-propionsäure als neuer entzündungshemmender Stoff wird beschrieben.