“Die Reliquien der kuhköpfigen Göttin in Byblos”

Studie zur Überlieferung des Philo Byblius und seinen Schilderungen betreffs Insignien und Reliquien der Herrin von Byblos in Gbeil

Who Ate Whom? Adaptive Helicobacter Genomic Changes That Accompanied a Host Jump from Early Humans to Large Felines

Helicobacter pylori infection of humans is so old that its population genetic structure reflects that of ancient human migrations. A closely related species, Helicobacter acinonychis, is specific for large felines, including cheetahs, lions, and tigers, whereas hosts more closely related to humans harbor more distantly related Helicobacter species. This observation suggests a jump between host species. But who ate whom and when did it happen? In order to resolve this question, we determined the genomic sequence of H. acinonychis strain Sheeba and compared it to genomes from H. pylori. The conserved core genes between the genomes are so similar that the host jump probably occurred within the last 200,000 (range 50,000–400,000) years. However, the Sheeba genome also possesses unique features that indicate the direction of the host jump, namely from early humans to cats. Sheeba possesses an unusually large number of highly fragmented genes, many encoding outer membrane proteins, which may have been destroyed in order to bypass deleterious responses from the feline host immune system. In addition, the few Sheeba-specific genes that were found include a cluster of genes encoding sialylation of the bacterial cell surface carbohydrates, which were imported by horizontal genetic exchange and might also help to evade host immune defenses. These results provide a genomic basis for elucidating molecular events that allow bacteria to adapt to novel animal hosts

mlr3proba: An R Package for Machine Learning in Survival Analysis

As machine learning has become increasingly popular over the last few decades, so too has the number of machine learning interfaces for implementing these models. Whilst many R libraries exist for machine learning, very few offer extended support for survival analysis. This is problematic considering its importance in fields like medicine, bioinformatics, economics, engineering, and more. mlr3proba provides a comprehensive machine learning interface for survival analysis and connects with mlr3's general model tuning and benchmarking facilities to provide a systematic infrastructure for survival modeling and evaluation.Comment: Submitted to Bioinformatic

Gain and Loss of Multiple Genes During the Evolution of Helicobacter pylori

Sequence diversity and gene content distinguish most isolates of Helicobacter pylori. Even greater sequence differences differentiate distinct populations of H. pylori from different continents, but it was not clear whether these populations also differ in gene content. To address this question, we tested 56 globally representative strains of H. pylori and four strains of Helicobacter acinonychis with whole genome microarrays. Of the weighted average of 1,531 genes present in the two sequenced genomes, 25% are absent in at least one strain of H. pylori and 21% were absent or variable in H. acinonychis. We extrapolate that the core genome present in all isolates of H. pylori contains 1,111 genes. Variable genes tend to be small and possess unusual GC content; many of them have probably been imported by horizontal gene transfer. Phylogenetic trees based on the microarray data differ from those based on sequences of seven genes from the core genome. These discrepancies are due to homoplasies resulting from independent gene loss by deletion or recombination in multiple strains, which distort phylogenetic patterns. The patterns of these discrepancies versus population structure allow a reconstruction of the timing of the acquisition of variable genes within this species. Variable genes that are located within the cag pathogenicity island were apparently first acquired en bloc after speciation. In contrast, most other variable genes are of unknown function or encode restriction/modification enzymes, transposases, or outer membrane proteins. These seem to have been acquired prior to speciation of H. pylori and were subsequently lost by convergent evolution within individual strains. Thus, the use of microarrays can reveal patterns of gene gain or loss when examined within a phylogenetic context that is based on sequences of core genes

Evaluation of LLNL's Nuclear Accident Dosimeters at the CALIBAN Reactor September 2010

The Lawrence Livermore National Laboratory uses neutron activation elements in a Panasonic TLD holder as a personnel nuclear accident dosimeter (PNAD). The LLNL PNAD has periodically been tested using a Cf-252 neutron source, however until 2009, it was more than 25 years since the PNAD has been tested against a source of neutrons that arise from a reactor generated neutron spectrum that simulates a criticality. In October 2009, LLNL participated in an intercomparison of nuclear accident dosimeters at the CEA Valduc Silene reactor (Hickman, et.al. 2010). In September 2010, LLNL participated in a second intercomparison of nuclear accident dosimeters at CEA Valduc. The reactor generated neutron irradiations for the 2010 exercise were performed at the Caliban reactor. The Caliban results are described in this report. The procedure for measuring the nuclear accident dosimeters in the event of an accident has a solid foundation based on many experimental results and comparisons. The entire process, from receiving the activated NADs to collecting and storing them after counting was executed successfully in a field based operation. Under normal conditions at LLNL, detectors are ready and available 24/7 to perform the necessary measurement of nuclear accident components. Likewise LLNL maintains processing laboratories that are separated from the areas where measurements occur, but contained within the same facility for easy movement from processing area to measurement area. In the event of a loss of LLNL permanent facilities, the Caliban and previous Silene exercises have demonstrated that LLNL can establish field operations that will very good nuclear accident dosimetry results. There are still several aspects of LLNL's nuclear accident dosimetry program that have not been tested or confirmed. For instance, LLNL's method for using of biological samples (blood and hair) has not been verified since the method was first developed in the 1980's. Because LLNL and the other DOE participants were limited in what they were allowed to do at the Caliban and Silene exercises and testing of various elements of the nuclear accident dosimetry programs cannot always be performed as guests at other sites, it has become evident that DOE needs its own capability to test nuclear accident dosimeters. Angular dependence determination and correction factors for NADs desperately need testing as well as more evaluation regarding the correct determination of gamma doses. It will be critical to properly design any testing facility so that the necessary experiments can be performed by DOE laboratories as well as guest laboratories. Alternate methods of dose assessment such as using various metals commonly found in pockets and clothing have yet to be evaluated. The DOE is planning to utilize the Godiva or Flattop reactor for testing nuclear accident dosimeters. LLNL has been assigned the primary operational authority for such testing. Proper testing of nuclear accident dosimeters will require highly specific characterization of the pulse fields. Just as important as the characterization of the pulsed fields will be the design of facilities used to process the NADs. Appropriate facilities will be needed to allow for early access to dosimeters to test and develop quick sorting techniques. These facilities will need appropriate laboratory preparation space and an area for measurements. Finally, such a facility will allow greater numbers of LLNL and DOE laboratory personnel to train on the processing and interpretation of nuclear accident dosimeters and results. Until this facility is fully operational for test purposes, DOE laboratories may need to continue periodic testing as guests of other reactor facilities such as Silene and Caliban

The Helicobacter pylori HpyAXII restriction–modification system limits exogenous DNA uptake by targeting GTAC sites but shows asymmetric conservation of the DNA methyltransferase and restriction endonuclease components

The naturally competent organism Helicobacter pylori encodes a large number of restriction–modification (R–M) systems that consist of a restriction endonuclease and a DNA methyltransferase. R–M systems are not only believed to limit DNA exchange among bacteria but may also have other cellular functions. We report a previously uncharacterized H. pylori type II R–M system, M.HpyAXII/R.HpyAXII. We show that this system targets GTAC sites, which are rare in the H. pylori chromosome but numerous in ribosomal RNA genes. As predicted, this type II R–M system showed attributes of a selfish element. Deletion of the methyltransferase M.HpyAXII is lethal when associated with an active endonuclease R.HpyAXII unless compensated by adaptive mutation or gene amplification. R.HpyAXII effectively restricted both unmethylated plasmid and chromosomal DNA during natural transformation and was predicted to belong to the novel ‘half pipe’ structural family of endonucleases. Analysis of a panel of clinical isolates revealed that R.HpyAXII was functional in a small number of H. pylori strains (18.9%, n = 37), whereas the activity of M.HpyAXII was highly conserved (92%, n = 50), suggesting that GTAC methylation confers a selective advantage to H. pylori. However, M.HpyAXII activity did not enhance H. pylori fitness during stomach colonization of a mouse infection model