Ubiquitous LEA29Y Expression Blocks T Cell Co-Stimulation but Permits Sexual Reproduction in Genetically Modified Pigs

We have successfully established and characterized a genetically modified pig line with ubiquitous expression of LEA29Y, a human CTLA4-Ig derivate. LEA29Y binds human B7.1/CD80 and B7.2/CD86 with high affinity and is thus a potent inhibitor of T cell co-stimulation via this pathway. We have characterized the expression pattern and the biological function of the transgene as well as its impact on the porcine immune system and have evaluated the potential of these transgenic pigs to propagate via assisted breeding methods. The analysis of LEA29Y expression in serum and multiple organs of CAG-LEA transgenic pigs revealed that these animals produce a biologically active transgenic product at a considerable level. They present with an immune system affected by transgene expression, but can be maintained until sexual maturity and propagated by assisted reproduction techniques. Based on previous experience with pancreatic islets expressing LEA29Y, tissues from CAG-LEA29Y transgenic pigs should be protected against rejection by human T cells. Furthermore, their immune-compromised phenotype makes CAG-LEA29Y transgenic pigs an interesting large animal model for testing human cell therapies and will provide an important tool for further clarifying the LEA29Y mode of action

An integrative approach for building personalized gene regulatory networks for precision medicine

Only a small fraction of patients respond to the drug prescribed to treat their disease, which means that most are at risk of unnecessary exposure to side effects through ineffective drugs. This inter-individual variation in drug response is driven by differences in gene interactions caused by each patient's genetic background, environmental exposures, and the proportions of specific cell types involved in disease. These gene interactions can now be captured by building gene regulatory networks, by taking advantage of RNA velocity (the time derivative of the gene expression state), the ability to study hundreds of thousands of cells simultaneously, and the falling price of single-cell sequencing. Here, we propose an integrative approach that leverages these recent advances in single-cell data with the sensitivity of bulk data to enable the reconstruction of personalized, cell-type- and context-specific gene regulatory networks. We expect this approach will allow the prioritization of key driver genes for specific diseases and will provide knowledge that opens new avenues towards improved personalized healthcare

Fast decision in favor of the slow fission process

The fission probability P-f of highly excited targetlike nuclei produced in reactions of 2.5 GeV protons on Au, Bi, and U was studied as a function of excitation energy E-* whereby E-* is deduced eventwise from the multiplicity of evaporated light particles. At the highest E-* of 1000 MeV P-f amounts to approximate to 30% with all 3 target nuclei irrespective of the initial fissility. Statistical-model calculations satisfactorily reproduce the observed evolution of P-f with E-*-provided that no extra transient delay is introduced. Fission thus is decided upon very fast and early in the long deexcitation chain towards scission which comprises as much as approximate to 80% of all evaporated alpha particles

Study of ternary and quaternary spontaneous fission of sup 2 sup 5 sup 2 Cf with the NESSI detector

Ternary and quaternary spontaneous decay of sup 2 sup 5 sup 2 Cf was studied with the NESSI detector, a combination of two 4 pi detectors for charged particles, neutrons and gamma-rays. The applied method of particle identification by measuring the energies and relative time-of-flights of the decay products is shown to be very effective for the study of rare decay modes. The energy and angular distributions of the decay products, the associated neutron multiplicities, the total energy of the prompt gamma-radiation as well as correlations between the various observables were measured for the first time in a single full-scale experiment. The characteristics of ternary fission known from previous investigations are confirmed in the frame of a methodically independent experiment. Preliminary estimates of the quaternary fission yield are presented. An attempt is made to determine the mechanism of quaternary fission

Study of ternary and quaternary spontaneous fission of "2"5"2Cf with the NESSI detector

Ternary and quaternary spontaneous decay of "2"5"2Cf was studied with the NESSI detector, a combination of two 4#pi# detectors for charged particles, neutrons and #gamma#-rays. The applied method of particle identification by measuring the energies and relative time-of-flights of the decay products is shown to be very effective for the study of rare decay modes. The energy and angular distributions of the decay products, the associated neutron multiplicities, the total energy of the prompt #gamma#-radiation as well as correlations between the various observables were measured for the first time in a single full-scale experiment. The characteristics of ternary fission known from previous investigations are confirmed in the frame of a methodically independent experiment. Preliminary estimates of the quaternary fission yield are presented. An attempt is made to determine the mechanism of quaternary fission. (orig.)SIGLEAvailable from TIB Hannover: ZA 4746(588) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman