Constitutive expression of the pre-TCR enables development of mature T cells

Expression and signalling through the pre-TCR and the TCRαβ resemble two critical checkpoints during T cell development. We investigated to which extent a pre-TCR can functionally replace mature TCRα chains during T cell development. For this purpose, transgenic mice were generated expressing the pre-TCRα (pTα) under the transcriptional control of TCRβ regulatory elements. We report here on the interesting finding that constitutive pTα expression allows complete T cell maturation. The pre-TCR complex permits a subset of β-selected thymocytes to mature in the absence of TCRα into peripheral T cells (βT cells) comprising up to 10% of all lymphocytes. Lymphopenia-driven proliferation of these βT cells is similar to that of conventional αβT cells. Furthermore, βT cells proliferated and acquired effector function upon stimulation with allogeneic MH

How does transverse (hydrodynamic) flow affect jet-broadening and jet-quenching ?

We give the modification of formulas for $p_{\perp}$-broadening and energy loss which are necessary to calculate parton interactions in a medium with flow. Arguments are presented leading to the conclusion that for large $p_{\perp}$-spectra observed in heavy ion collisions at RHIC, the influence of transverse flow on the determination of the "quenching power" of the produced medium is small. This leaves open the question of the interpretation of data in a consistent perturbative framework.Comment: 8 pages and 4 figures; version v2 includes more consistent notations and correction of fig.2; version v3 contains a misprint correction, an added sentence in section 3C and in the Introduction as well as in section 4 a rephrasing of comments about references [31,32,35

Strange Messages: Chemical and Thermal Freeze-out in Nuclear Collisions

Thermal models are commonly used to interpret heavy-ion data on particle yields and spectra and to extract the conditions of chemical and thermal freeze-out in heavy-ion collisions. I discuss the usefulness and limitations of such thermal model analyses and review the experimental and theoretical evidence for thermalization in nuclear collisions. The crucial role of correlating strangeness production data with single particle spectra and two-particle correlation measurements is pointed out. A consistent dynamical picture for the heavy-ion data from the CERN SPS involves an initial prehadronic stage with deconfined color and with an appreciable isotropic pressure component. This requires an early onset of thermalization.Comment: 15 pages, 2 figures, talk given at Strange Quark Matter '98, Padova, Italy, 20-24 July 1998, to be published in J. Phys. G 25; final version with updated reference

PCNA Ubiquitination Is Important, But Not Essential for Translesion DNA Synthesis in Mammalian Cells

Translesion DNA synthesis (TLS) is a DNA damage tolerance mechanism in which specialized low-fidelity DNA polymerases bypass replication-blocking lesions, and it is usually associated with mutagenesis. In Saccharomyces cerevisiae a key event in TLS is the monoubiquitination of PCNA, which enables recruitment of the specialized polymerases to the damaged site through their ubiquitin-binding domain. In mammals, however, there is a debate on the requirement for ubiquitinated PCNA (PCNA-Ub) in TLS. We show that UV-induced Rpa foci, indicative of single-stranded DNA (ssDNA) regions caused by UV, accumulate faster and disappear more slowly in Pcna(K164R/K164R) cells, which are resistant to PCNA ubiquitination, compared to Pcna(+/+) cells, consistent with a TLS defect. Direct analysis of TLS in these cells, using gapped plasmids with site-specific lesions, showed that TLS is strongly reduced across UV lesions and the cisplatin-induced intrastrand GG crosslink. A similar effect was obtained in cells lacking Rad18, the E3 ubiquitin ligase which monoubiquitinates PCNA. Consistently, cells lacking Usp1, the enzyme that de-ubiquitinates PCNA exhibited increased TLS across a UV lesion and the cisplatin adduct. In contrast, cells lacking the Rad5-homologs Shprh and Hltf, which polyubiquitinate PCNA, exhibited normal TLS. Knocking down the expression of the TLS genes Rev3L, PolH, or Rev1 in Pcna(K164R/K164R) mouse embryo fibroblasts caused each an increased sensitivity to UV radiation, indicating the existence of TLS pathways that are independent of PCNA-Ub. Taken together these results indicate that PCNA-Ub is required for maximal TLS. However, TLS polymerases can be recruited to damaged DNA also in the absence of PCNA-Ub, and perform TLS, albeit at a significantly lower efficiency and altered mutagenic specificity

DNA Double Strand Breaks Occur Independent of AID in Hypermutating Ig Genes

Somatic hypermutation (SHM) and class switch recombination (CSR) take place in B cells of the germinal center (GC) and are associated with DNA double-strand breaks (DNA-DSBs). Transcription favors the generation of DNA-DSBs in the V-regions and switch regions of Ig genes. Both SHM and CSR are controlled by the Activation Induced Cytidine Deaminase (AID), an enzyme exclusively expressed in B cells of the GC. Because AID is capable of deaminating deoxy-cytidine (dC) to deoxy-uracil (dU), it might directly induce nicks (single strand DNA breaks) and also DNA-DSBs via a U-DNA glycosylase mediated base excision repair pathway ('DNA-substrate model'). Alternatively, AID could function like its closest homologue Apobec-1 as a catalytic subunit of a RNA editing holoenzyme ('RNA-substrate model'). To determine whether AID lies upstream or downstream of the DNA lesions found in hypermutating Ig genes, we have analysed the Vλ locus of AID proficient and AID deficient GC B cells for the presence of DNA-DSBs. Although rearranged Vλ genes are preferred targets of SHM we find that AID-proficient and -deficient Vλ1/2-expressing GC B cells display a similar frequency, distribution and sequence preference of DNA-DSBs in rearranged and germline Vλ genes, favoring the idea that AID acts downstream of the DNA lesions to mediate error prone processing

Thoughts on opportunities in high-energy nuclear collisions

This document reflects thoughts on opportunities from high-energy nuclear collisions in the 2020s.Comment: 10 pages, pd

DISTO data on Kpp

The data from the DISTO Collaboration on the exclusive pp -> p K+ Lambda production acquired at T_p = 2.85 GeV have been re-analysed in order to search for a deeply bound K- pp (= X) state, to be formed in the binary process pp -> K+ X. The preliminary spectra of the DeltaM_{K+} missing-mass and of the M_{p Lambda} invariant-mass show, for large transverse-momenta of protons and kaons, a distinct broad peak with a mass M_X = 2265 +- 2 MeV/c^2 and a width Gamma_X = 118 +- 8 MeV/c^2.Comment: 8 pages, 4 figures. Talk presented at the "10th International Conference on Hypernuclear and Strange Particle Physics" (HYP-X), Tokai, Ibaraki, Japan, September 14th-18th, 2009. To appear in the proceeding

Parton energy loss in an expanding quark-gluon plasma: Radiative vs collisional

We perform a comparison of the radiative and collisional parton energy losses in an expanding quark-gluon plasma. The radiative energy loss is calculated within the light-cone path integral approach. The collisional energy loss is calculated using the Bjorken method with an accurate treatment of the binary collision kinematics. Our numerical results demonstrate that for RHIC and LHC conditions the collisional energy loss is relatively small in comparison to the radiative one. We find an enhancement of the heavy quark radiative energy loss as compared to that of the light quarks at high energies.Comment: 13 pages, 3 figure