14-3-3 Proteins Regulate Exonuclease 1–Dependent Processing of Stalled Replication Forks

Replication fork integrity, which is essential for the maintenance of genome stability, is monitored by checkpoint-mediated phosphorylation events. 14-3-3 proteins are able to bind phosphorylated proteins and were shown to play an undefined role under DNA replication stress. Exonuclease 1 (Exo1) processes stalled replication forks in checkpoint-defective yeast cells. We now identify 14-3-3 proteins as in vivo interaction partners of Exo1, both in yeast and mammalian cells. Yeast 14-3-3–deficient cells fail to induce Mec1–dependent Exo1 hyperphosphorylation and accumulate Exo1–dependent ssDNA gaps at stalled forks, as revealed by electron microscopy. This leads to persistent checkpoint activation and exacerbated recovery defects. Moreover, using DNA bi-dimensional electrophoresis, we show that 14-3-3 proteins promote fork progression under limiting nucleotide concentrations. We propose that 14-3-3 proteins assist in controlling the phosphorylation status of Exo1 and additional unknown targets, promoting fork progression, stability, and restart in response to DNA replication stress

Cancer-Specific Mortality, Cure Fraction, and Noncancer Causes of Death Among Diffuse Large B-cell Lymphoma Patients in the Immunochemotherapy Era.

BACKGROUND Survival after the diagnosis of diffuse large B-cell lymphoma (DLBCL) has been increasing since 2002 because of improved therapies; however, long-term outcomes for these patients in the modern treatment era are still unknown. METHODS Using Surveillance, Epidemiology, and End Results data, this study first assessed factors associated with DLBCL-specific mortality during 2002-2012. An epidemiologic risk profile, based on clinical and demographic characteristics, was used to stratify DLBCL cases into low-, medium-, and high-risk groups. The proportions of DLBCL cases that might be considered cured in these 3 risk groups was estimated. Risks of death due to various noncancer causes among DLBCL cases versus the general population were also calculated with standardized mortality ratios (SMRs). RESULTS Overall, 8274 deaths were recorded among 18,047 DLBCL cases; 76% of the total deaths were attributed to DLBCL, and 24% were attributed to noncancer causes. The 10-year survival rates for the low-, medium-, and high-risk groups were 80%, 60%, and 36%, respectively. The estimated cure proportions for the low-, medium-, and high-risk groups were 73%, 49%, and 27%, respectively; however, these cure estimates were uncertain because of the need to extrapolate the survival curves beyond the follow-up time. Mortality risks calculated with SMRs were elevated for conditions including vascular diseases (SMR, 1.3), infections (SMR, 3.1), gastrointestinal diseases (SMR, 2.5), and blood diseases (SMR, 4.6). These mortality risks were especially high within the initial 5 years after the diagnosis and declined after 5 years. CONCLUSIONS Some DLBCL patients may be cured of their cancer, but they continue to experience excess mortality from lymphoma and other noncancer causes. Cancer 2017. © 2017 American Cancer Society

Symmetric Versus Nonsymmetric Structure of the Phosphorus Vacancy on InP(110)

The atomic and electronic structure of positively charged P vacancies on InP(110) surfaces is determined by combining scanning tunneling microscopy, photoelectron spectroscopy, and density-functional theory calculations. The vacancy exhibits a nonsymmetric rebonded atomic configuration with a charge transfer level 0.75+-0.1 eV above the valence band maximum. The scanning tunneling microscopy (STM) images show only a time average of two degenerate geometries, due to a thermal flip motion between the mirror configurations. This leads to an apparently symmetric STM image, although the ground state atomic structure is nonsymmetric.Comment: 5 pages including 3 figures. related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Evidence for the tensor meson exchange in the kaon photoproduction

The contribution of the tensor meson $K_2^*(1430)$ exchange in the process $\gamma p\to K^+\Lambda(\Sigma^0)$ is investigated within the Regge framework. Inclusion of the $K_2^*$ exchange in the $K(494)+K^*(892)$ exchanges with the coupling constants chosen from the SU(3) symmetry leads to a better description of the production mechanism without referring to any fitting procedure. This shows the significance of the role of the tensor meson exchange to have the Regge theory basically free of parameters with the SU(3) symmetry a good approximation for the meson-baryon couplings.Comment: 5 pages, 4 figures, 2 table

Evaporation and Condensation of Clusters

Influence of surrounding matter on the properties of clusters is considered by an approach combining the methods of statistical and quantum mechanics. A cluster is treated as a bound N-particle system and surrounding matter as thermostat. It is shown that, despite arbitrary strong interactions between particles, cluster energy can be calculated by using the controlled perturbation theory. The accuracy of the latter is found to be much higher than that of the quasiclassical approximation. Spectral distribution is obtained by minimizing conditional entropy. Increasing the thermostat temperature leads to the depletion of bound states. The characteristic temperature when bound states become essentially depleated defines the temperature of cluster evaporation. The inverse process of lowering the thermostate temperature, yielding the filling of bound states, corresponds to cluster condensation.Comment: 1 file, 15 pages, RevTex, 4 table

A Polymerase-chain-reaction Assay for the Specific Identification of Transcripts Encoded by Individual Carcinoembryonic Antigen (CEA)-gene-family Members

Carcinoembryonic antigen (CEA) is a tumor marker that belongs to a family of closely related molecules with variable expression patterns. We have developed sets of oligonucleotide primers for the specific amplification of transcripts from individual CEA-family members using the reverse transcriptase/ polymerase chain reaction (RT/PCR). Specific primer sets were designed for CEA, non-specific cross-reacting antigen (NCA), biliary glycoprotein (BGP), carcinoembryonic antigen gene-family members 1, 6 and 7 (CGMI, CGM6 and CGM7), and one set for all pregnancy-specific glycoprotein (PSG) transcripts. Primers were first tested for their specificity against individual cDNA clones and product-hybridization with internal, transcript-specific oligonucleotides. Total RNA from 12 brain and 63 gynecological tumors were then tested for expression of CEA-related transcripts. None were found in tumors located in the brain, including various mesenchymal and neuro-epithelial tumors. CEA and NCA transcripts were, however, present in an adenocarcinoma located in the nasal sinuses. In ovarian mucinous adenocarcinomas, we always found co-expression of CEA and NCA transcripts, and occasionally BGP mRNA. CEA-related transcripts were also found in some serous, endometrioid and clear-cell ovarian carcinomas. CEA, NCA and BGP transcripts were present in endometrial carcinomas of the uterus and cervical carcinomas, whereas uterine leiomyomas were completely negative. No transcripts were found from CGM 1, CGM6, CGM7 or from PSG genes in any of the tumors tested. The PCR data were compared with immunohistochemical investigations of ovarian tumors at the protein level using CEA (26/3/13)-, NCA-50/90 (9A6FR) and NCA-95 (80H3)-specific monoclonal antibodies

Dual Targeting of Cell Wall Precursors by Teixobactin Leads to Cell Lysis

ABSTRACT Teixobactin represents the first member of a newly discovered class of antibiotics that act through inhibition of cell wall synthesis. Teixobactin binds multiple bactoprenol-coupled cell wall precursors, inhibiting both peptidoglycan and teichoic acid synthesis. Here, we show that the impressive bactericidal activity of teixobactin is due to the synergistic inhibition of both targets, resulting in cell wall damage, delocalization of autolysins, and subsequent cell lysis. We also find that teixobactin does not bind mature peptidoglycan, further increasing its activity at high cell densities and against vancomycin-intermediate Staphylococcus aureus (VISA) isolates with thickened peptidoglycan layers. These findings add to the attractiveness of teixobactin as a potential therapeutic agent for the treatment of infection caused by antibiotic-resistant Gram-positive pathogens

Cross-lagged associations between depressive symptoms and response style in adolescents

Depressive disorders are highly prevalent during adolescence and they are a major concern for individuals and society. The Response Style Theory and the Scar Theory both suggest a relationship between response styles and depressive symptoms, but the theories differ in the order of the development of depressive symptoms. Longitudinal reciprocal prospective relationships between depressive symptoms and response styles were examined in a community sample of 1343 adolescents. Additionally, response style was constructed with the traditional approach, which involves examining three response styles separately without considering the possible relations between them, and with the ratio approach, which accounts for all three response styles simultaneously. No reciprocal relationships between depressive symptoms and response style were found over time. Only longitudinal relationships between response style and depressive symptoms were significant. This study found that only depressive symptoms predicted response style, whereas the response style did not emerge as an important underlying mechanism responsible for developing and maintaining depressive symptoms in adolescents. These findings imply that prevention and intervention programs for adolescents with low depressive symptoms should not focus on adaptive and maladaptive response style strategies to decrease depressive symptoms, but should focus more on behavioral interventions

Mycobacterium tuberculosis ClpP Proteases Are Co-transcribed but Exhibit Different Substrate Specificities

PMCID: PMC3613350This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Thermodynamics of lattice QCD with two light quark flavours on a 16^3 x 8 lattice II

We have extended our earlier simulations of the high temperature behaviour of lattice QCD with two light flavours of staggered quarks on a $16^3 \times 8$ lattice to lower quark mass (m_q=0.00625). The transition from hadronic matter to a quark-gluon plasma is observed at $6/g^2=5.49(2)$ corresponding to a temperature of $T_c \approx 140$MeV. We present measurements of observables which probe the nature of the quark-gluon plasma and serve to distinguish it from hadronic matter. Although the transition is quite abrupt, we have seen no indications that it is first order.Comment: 23 pages, RevteX, 6 encapsulated postscript figure