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Abstract Peroxiredoxin (Prx) is an important antioxidant defense enzyme that reduces hydrogen peroxide to molecular oxygen by using reducing equivalents from thioredoxin. We report that lung Prx I messenger RNA (mRNA) is specifically upregulated by oxygen. Throughout the third trimester, mRNA for Prx I was expressed constitutively at low levels in fetal baboon lung. However, after premature birth (125 or 140 d gestation), lung Prx I mRNA increased rapidly with the onset of oxygen exposure. Premature animals (140 d) breathing 100% O2 developed chronic lung disease within 7 to 14 d. These animals had greater lung Prx I mRNA after 1, 6, or 10 d of life than did fetal controls. In 140-d animals given lesser O2 concentrations (as needed) that did not develop chronic lung disease, lung Prx I mRNA also was increased on Days 1 and 6, but not Day 10. In fetal distal lung explant culture, Prx I mRNA was elevated in 95% O2, relative to 1% oxygen, and remained elevated at 24 h. Prx protein activity increased in 140-d premature baboons exposed to as-needed oxygen. By contrast, there was a decrease in Prx activity in 140-d premature baboons exposed to 100% oxygen. In the lung explants from prematures (140 d), there was no significant increase in Prx activity in response to 24 h exposure to hyperoxia, whereas exposure of explants to 48 h hyperoxia caused a nonsignificant decrease in Prx activity. Treatment of lung explants with actinomycin D inhibited Prx mRNA increases in 95% oxygen, indicating transcriptional regulation. In cellular signaling studies we demonstrated that protein kinase (PK) C activity increased when A549 cells were exposed to 95% oxygen, compared with 21% oxygen exposure. In lung explant cultures, specific PKC inhibitors calphostin C or GF109203X inhibited the increase in Prx I mRNA with 95% oxygen exposure, indicating PKC-mediated signaling. The acute increase in gene expression of Prx I in response to oxygen suggests an important role for this protein during the transition from relatively anaerobic fetal life to oxygen-breathing at birth.

A major goal of cancer chemotherapy is the identification of cytotoxic compounds that are highly selective for cancer cells. We describe here one such compound - a novel iron chelator, desferri-exochelin 772SM. This desferri-exochelin has unique chemical and pharmacological properties, including extremely high iron binding affinity, the capacity to block iron-mediated redox reactions, and lipid solubility which enables it to enter cells rapidly. At low concentrations, this desferri-exochelin kills T47D-YB and MCF-7 human breast cancer cells by inducing apoptosis, but only reversibly arrests the growth of normal human mammary epithelial cells without cytotoxicity. Since iron-loaded exochelin is ineffective, iron chelation accounts for the efficacy of desferri-exochelin. For both the killing of breast cancer cells and the growth arrest of normal breast epithelial cells, desferri-exochelin was effective at much lower concentrations than the lipid-insoluble iron chelator deferoxamine, which has shown only limited potential as an anti-cancer agent. Growth arrest of progesterone receptor positive T47D-YB cells with the progestin R5020 transiently protects them from the cytotoxic effects of desferri-exochelin, but the cells are killed after cell growth resumes. Similarly, MCF-7 cells arrested with the estrogen antagonist ICI182780 are transiently resistant to killing by desferri-exochelin. Thus the desferri-exochelin is cytotoxic only to actively growing tumor cells. Since desferri-exochelin 772SM can selectively and efficiently destroy proliferating cancer cells without damaging normal cells, it may prove useful for the treatment of cancer.

Cdc7p is a protein kinase that is G1/S transition and initiation of DNA replication in Saccharomyces cerevisiae. The mechanisms whereby Cdc7p and its substrates exerts their effects are unknown. We report bite the characterization in S. cerevisiae of a recessive mutation in a member of the MCM family MCM5/CDC46, which bypasses the requirement for Cdc7p and its interacting factor Dbf4p. Because the MCM family of evolutionarily conserved proteins have been implicated in restricting DNA replication to once per cell cycle, our studies suggest that Cdc7p is required late in G1 because in its absence the Mcm5p/Cdc46p blocks the initiation of DNA replication. Moreover, Mcm5p/Cdc46p may have both positive and negative effects on the ability of cell to initiate replication

Inclusive jet, dijet and trijet differential cross sections are measured in neutral current deep-inelastic scattering for exchanged boson virtualities ... using the H1 detector at HERA. The data were taken in the years 2003 to 2007 and correspond to an integrated luminosity of ... Double differential Jet cross sections are obtained using a regularised unfolding procedure. They are presented as a function of ... and the transverse momentum of the jet, ..., and as a function of ... and the proton's longitudinal momentum fraction, ..., carried by the parton participating in the hard interaction. In addition normalised double differential jet cross sections are measured as the ratio of the jet cross sections to the inclusive neutral current cross sections in the respective ... bins of the jet measurements. Compared to earlier work, the measurements benefit from an improved reconstruction and calibration of the hadronic final state. The cross sections are compared to perturbative QCD calculations in next-to-leading order and are used to determine the running coupling and the value of the strong coupling constant as ...

(ProQuest: ... denotes formulae and/or non-USASCII text omitted; see image) Inclusive ... double differential cross sections for neutral current deep inelastic scattering are measured with the H1 detector at HERA. The data were taken with a lepton beam energy of ... GeV and two proton beam energies of ... and 575 GeV corresponding to centre-of-mass energies of 225 and 252 GeV, respectively. The measurements cover the region of ... for ... GeV... up to ... The measurements are used together with previously published H1 data at ... GeV and lower ... data at ..., ... and ... GeV to extract the longitudinal proton structure function ... in the region ... GeV...

Inclusive ep double differential cross sections for neutral current deep inelastic scattering are measured with the H1 detector at HERA. The data were taken with a lepton beam energy of 27.6 GeV and two proton beam energies of Ep = 460 and 575 GeV corresponding to centre-of-mass energies of 225 and 252 GeV, respectively. The measurements cover the region of 6.5 *10⁻4<=x<= 0.65 for 35<=Q²<=800 GeV² up to y = 0.85. The measurements are used together with previously published H1 data at Ep = 920 GeV and lower Q2 data at Ep = 460, 575 and 920 GeV to extract the longitudinal proton structure function FL in the region 1.5<=Q² <=800 GeV².

(ProQuest: ... denotes formulae and/or non-USASCII text omitted; see image) Cross sections for elastic and proton-dissociative photoproduction of J/ψ mesons are measured with the H1 detector in positron-proton collisions at HERA. The data were collected at ep centre-of-mass energies ... and ..., corresponding to integrated luminosities of ... and ..., respectively. The cross sections are measured as a function of the photon-proton centre-of-mass energy in the range 25

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