Observations of ozone and related species in the northeast Pacific during the PHOBEA campaigns 2. Airborne observations

During late March and April of 1999 the University of Wyoming's King Air research aircraft measured atmospheric concentrations of NO, O3, peroxyacetyl nitrate (PAN), CO, CH4, VOCs, aerosols, and J(NO2) off the west coast of the United States. During 14 flights, measurements were made between 39°-48° N latitude, 125°-129° W longitude, and at altitudes from 0-8 km. These flights were part of the Photochemical Ozone Budget of the Eastern North Pacific Atmosphere (PHOBEA) experiment, which included both ground-based and airborne measurements. Flights were scheduled when meteorological conditions minimized the impact of local pollution sources. The resulting measurements were segregated by air mass source region as indicated by back isentropic trajectory analysis. The chemical composition of marine air masses whose 5-day back isentropic trajectories originated north of 40° N latitude or west of 180° W longitude (WNW) differed significantly from marine air masses whose 5-day back isentropic trajectories originated south of 40° N latitude and east of 180° W longitude (SW). Trajectory and chemical analyses indicated that the majority of all encountered air masses, both WNW and SW, likely originated from the northwestern Pacific and have characteristics of emissions from the East Asian continental region. However, air masses with WNW back trajectories contained higher mixing ratios of NO, NOx, O3, PAN, CO, CH4, various VOC pollution tracers, and aerosol number concentration, compared to those air masses with SW back trajectories. Calculations of air mass age using two separate methods, photochemical and back trajectory, are consistent with transport from the northwestern Pacific in 8-10 days for air masses with WNW back trajectories and 16-20 days for air masses with SW back trajectories. Correlations, trajectory analysis, and comparisons with measurements made in the northwestern Pacific during NASA's Pacific Exploritory Mission-West Phase B (PEM-West B) experiment in 1994 are used to investigate the data. These analyses provide evidence that anthropogenically influenced air masses from the northwestern Pacific affect the overall chemical composition of the northeastern Pacific troposphere. Copyright 2001 by the American Geophysical Union

Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5.

Pdr5, a member of the extensive ABC transporter superfamily, is representative of a clinically relevant subgroup involved in pleiotropic drug resistance. Pdr5 and its homologues drive drug efflux through uncoupled hydrolysis of nucleotides, enabling organisms such as baker's yeast and pathogenic fungi to survive in the presence of chemically diverse antifungal agents. Here, we present the molecular structure of Pdr5 solved with single particle cryo-EM, revealing details of an ATP-driven conformational cycle, which mechanically drives drug translocation through an amphipathic channel, and a clamping switch within a conserved linker loop that acts as a nucleotide sensor. One half of the transporter remains nearly invariant throughout the cycle, while its partner undergoes changes that are transmitted across inter-domain interfaces to support a peristaltic motion of the pumped molecule. The efflux model proposed here rationalises the pleiotropic impact of Pdr5 and opens new avenues for the development of effective antifungal compounds.Open Access funding enabled and organized by Projekt DEAL

Notch-induced T cell development requires phosphoinositide-dependent kinase 1

Phosphoinositide-dependent kinase l (PDK1) phosphorylates and activates multiple AGC serine kinases, including protein kinase B (PKB), p70Ribosomal S6 kinase (S6K) and p90Ribosomal S6 kinase (RSK). PDK1 is required for thymocyte differentiation and proliferation, and herein, we explore the molecular basis for these essential functions of PDK1 in T lymphocyte development. A key finding is that PDK1 is required for the expression of key nutrient receptors in T cell progenitors: CD71 the transferrin receptor and CD98 a subunit of L-amino acid transporters. PDK1 is also essential for Notch-mediated trophic and proliferative responses in thymocytes. A PDK1 mutant PDK1 L155E, which supports activation of PKB but no other AGC kinases, can restore CD71 and CD98 expression in pre-T cells and restore thymocyte differentiation. However, PDK1 L155E is insufficient for thymocyte proliferation. The role of PDK1 in thymus development thus extends beyond its ability to regulate PKB. In addition, PDK1 phosphorylation of AGC kinases such as S6K and RSK is also necessary for thymocyte development

Identification of a novel type of spacer element required for imprinting in fission yeast

Asymmetrical segregation of differentiated sister chromatids is thought to be important for cellular differentiation in higher eukaryotes. Similarly, in fission yeast, cellular differentiation involves the asymmetrical segregation of a chromosomal imprint. This imprint has been shown to consist of two ribonucleotides that are incorporated into the DNA during laggingstrand synthesis in response to a replication pause, but the underlying mechanism remains unknown. Here we present key novel discoveries important for unravelling this process. Our data show that cis-acting sequences within the mat1 cassette mediate pausing of replication forks at the proximity of the imprinting site, and the results suggest that this pause dictates specific priming at the position of imprinting in a sequence-independent manner. Also, we identify a novel type of cis-acting spacer region important for the imprinting process that affects where subsequent primers are put down after the replication fork is released from the pause. Thus, our data suggest that the imprint is formed by ligation of a not-fullyprocessed Okazaki fragment to the subsequent fragment. The presented work addresses how differentiated sister chromatids are established during DNA replication through the involvement of replication barriers

Stereotactic laser thermal ablation of mesial temporal lobe epilepsy with right hippocampal sclerosis—patient decision-making, realization and visualization of memory function

Zusammenfassung: Wir berichten über einen 30-jährigen Patienten, der mit 21 Jahren an einer fokalen Epilepsie mit epigastrischen Auren und nicht bewusst erlebten Anfällen sowie selten bilateralen tonisch-klonischen Anfällen mit Hippocampussklerose erkrankte. Dem Patienten wurde das resektive Standardverfahren (vordere Temporallappenresektion) sowie alternativ das neu in Europa zugelassene Verfahren der stereotaktischen Laserthermoablation angeboten. Der Patient entschied sich aufgrund der geringeren Invasivität für letzteres Verfahren. Im Folgenden werden der klinische Verlauf mit einer postoperativen Nachbeobachtungszeit von 9 Monaten berichtet. Zudem wird die Methode und die Ergebnisse einer funktionellen Gedächtnis-MRT Untersuchung beschrieben. / Abstract: This article reports about a 30-year-old male patient who had suffered from a focal epilepsy with epigastric auras, unaware seizures and rarely bilateral tonic clonic seizures due to hippocampal sclerosis since the age of 21 years. The patient was offered the standard anterior temporal lobe resection and alternatively stereotactic laser thermal ablation, which recently received approval with the European CE mark. The patient opted for stereotactic laser ablation because of its less invasive nature compared to standard craniotomy and resection. This article reports the clinical course over a 9-month follow-up period. Additionally, the method and the results of a functional magnetic resonance imaging (fMRI) memory examination are summarized

Lambda and Antilambda polarization from deep inelastic muon scattering

We report results of the first measurements of Lambda and Antilambda polarization produced in deep inelastic polarized muon scattering on the nucleon. The results are consistent with an expected trend towards positive polarization with increasing x_F. The polarizations of Lambda and Antilambda appear to have opposite signs. A large negative polarization for Lambda at low positive x_F is observed and is not explained by existing models.A possible interpretation is presented.Comment: 9 pages, 2 figure

Stromal Interferon-γ Signaling and Cross-Presentation Are Required to Eliminate Antigen-Loss Variants of B Cell Lymphomas in Mice

To study mechanisms of T cell-mediated rejection of B cell lymphomas, we developed a murine lymphoma model wherein three potential rejection antigens, human c-MYC, chicken ovalbumin (OVA), and GFP are expressed. After transfer into wild-type mice 60–70% of systemically growing lymphomas expressing all three antigens were rejected; lymphomas expressing only human c-MYC protein were not rejected. OVA expressing lymphomas were infiltrated by T cells, showed MHC class I and II upregulation, and lost antigen expression, indicating immune escape. In contrast to wild-type recipients, 80–100% of STAT1-, IFN-γ-, or IFN-γ receptor-deficient recipients died of lymphoma, indicating that host IFN-γ signaling is critical for rejection. Lymphomas arising in IFN-γ- and IFN-γ-receptor-deficient mice had invariably lost antigen expression, suggesting that poor overall survival of these recipients was due to inefficient elimination of antigen-negative lymphoma variants. Antigen-dependent eradication of lymphoma cells in wild-type animals was dependent on cross-presentation of antigen by cells of the tumor stroma. These findings provide first evidence for an important role of the tumor stroma in T cell-mediated control of hematologic neoplasias and highlight the importance of incorporating stroma-targeting strategies into future immunotherapeutic approaches

Old World Monkeys Compare to Apes in the Primate Cognition Test Battery

Understanding the evolution of intelligence rests on comparative analyses of brain sizes as well as the assessment of cognitive skills of different species in relation to potential selective pressures such as environmental conditions and social organization. Because of the strong interest in human cognition, much previous work has focused on the comparison of the cognitive skills of human toddlers to those of our closest living relatives, i.e. apes. Such analyses revealed that apes and children have relatively similar competencies in the physical domain, while human children excel in the socio-cognitive domain; in particular in terms of attention sharing, cooperation, and mental state attribution. To develop a full understanding of the evolutionary dynamics of primate intelligence, however, comparative data for monkeys are needed. We tested 18 Old World monkeys (long-tailed macaques and olive baboons) in the so-called Primate Cognition Test Battery (PCTB) (Herrmann et al. 2007, Science). Surprisingly, our tests revealed largely comparable results between Old World monkeys and the Great apes. Single comparisons showed that chimpanzees performed only better than the macaques in experiments on spatial understanding and tool use, but in none of the socio-cognitive tasks. These results question the clear-cut relationship between cognitive performance and brain size and – prima facie – support the view of an accelerated evolution of social intelligence in humans. One limitation, however, is that the initial experiments were devised to tap into human specific skills in the first place, thus potentially underestimating both true nonhuman primate competencies as well as species differences