An essential role for transmembrane TNF in the resolution of the inflammatory lesion induced by Leishmania major infection

TNF is an essential player in infections with Leishmania major, contributing to the control of the inflammatory lesion and, to a lesser degree, to parasite killing. However, the relative contribution of the soluble and transmembrane forms of TNF in these processes is unknown. To investigate the role of transmembrane TNF (mTNF) in the control of L. major infections, mTNF-knock-in (mTNF(Delta/Delta)) mice, which express functional mTNF but do not release soluble TNF, were infected with L. major, and the development of the inflammatory lesion and the immune response was compared to that occurring in L. major-infected TNF(-/-) and wild-type mice. mTNF(Delta/Delta) mice controlled the infection and resolved their inflammatory lesion as well as wild-type mice, a process associated with the early clearance of neutrophils at the site of parasite infection. In contrast, L. major-infected TNF(-/-) mice developed non-healing lesions, characterized by an elevated presence of neutrophils at the site of infection and partial control of parasite number within the lesions. Altogether, the results presented here demonstrate that mTNF, in absence of soluble TNF, is sufficient to control infection due to L. major, enabling the regulation of inflammation, and the optimal killing of Leishmania parasites at the site of infection.

Improvement of γ-ray energy resolution of LaBr3:Ce3+ scintillation detectors by Sr2+ and Ca2+ co-doping

Commercially available LaBr3:5% Ce3+ scintillators show with photomultiplier tube readout about 2.7% energy resolution for the detection of 662 keV γ-rays. Here we will show that by co-doping LaBr3:Ce3+ with Sr2+ or Ca2+ the resolution is improved to 2.0%. Such an improvement is attributed to a strong reduction of the scintillation light losses that are due to radiationless recombination of free electrons and holes during the earliest stages (1–10 ps) inside the high free charge carrier density parts of the ionization track.

Proteomic identification of in vivo substrates for matrix metalloproteinases 2 and 9 reveals a mechanism for resolution of inflammation.

Clearance of allergic inflammatory cells from the lung through matrix metalloproteinases (MMPs) is necessary to prevent lethal asphyxiation, but mechanistic insight into this essential homeostatic process is lacking. In this study, we have used a proteomics approach to determine how MMPs promote egression of lung inflammatory cells through the airway. MMP2- and MMP9-dependent cleavage of individual Th2 chemokines modulated their chemotactic activity; however, the net effect of complementing bronchoalveolar lavage fluid of allergen-challenged MMP2(-/-)/MMP9(-/-) mice with active MMP2 and MMP9 was to markedly enhance its overall chemotactic activity. In the bronchoalveolar fluid of MMP2(-/-)/MMP9(-/-) allergic mice, we identified several chemotactic molecules that possessed putative MMP2 and MMP9 cleavage sites and were present as higher molecular mass species. In vitro cleavage assays and mass spectroscopy confirmed that three of the identified proteins, Ym1, S100A8, and S100A9, were substrates of MMP2, MMP9, or both. Function-blocking Abs to S100 proteins significantly altered allergic inflammatory cell migration into the alveolar space. Thus, an important effect of MMPs is to differentially modify chemotactic bioactivity through proteolytic processing of proteins present in the airway. These findings provide a molecular mechanism to explain the enhanced clearance of lung inflammatory cells through the airway and reveal a novel approach to target new therapies for asthma.

Muon reconstruction efficiency and momentum resolution of the ATLAS experiment in proton-proton collisions at √s = 7 TeV in 2010

This paper presents a study of the performance of the muon reconstruction in the analysis of proton–proton collisions at √s = 7TeV at theLHC, recorded by the ATLAS detector in 2010. This performance is described in terms of reconstruction and isolation efficiencies and momentum resolutions for different classes of reconstructed muons. The results are obtained from an analysis of J/ψ meson and Z boson decays to dimuons, reconstructed from a data sample corresponding to an integrated luminosity of 40 pb−1. The measured performance is compared to Monte Carlo predictions and deviations from the predicted performance are discussed.

Nazis by Kraut: A playful application of moral self-licensing

Doing something moral gives one a license to do something immoral. This form of moral compen-sation is called “moral self-licensing”. Interestingly, the moral behavior can take place in another domain than the subsequent immoral behavior. For example, buying eco-friendly products gives one a license to steal. This article is based on the idea that a healthy diet has a moral dimension. As a consequence, consuming a healthy product should give one a license for immoral behavior. This research supports this hypothesis on a playful study. This study shows that drinking sauerkraut juice contributes to a stronger support of Nazi-esque right wing ideology than drinking either nothing or a less-healthy beverage (Nestea).

DRUG METABOLISM IN LIVER TUMORS: PURIFICATION AND CHARACTERIZATION OF NADPH-CYTOCHROME-P450 REDUCTASE AND THE RESOLUTION OF MULTIPLE FORMS OF CYTOCHROME P-450

The hydroxylation of N- and O-methyl drugs and a polycyclic hydrocarbon has been demonstrated in microsomes prepared from two transplantable Morris hepatomas (i.e., 7288C. t.c. and 5123 t.c.(H). The hydroxylation rates of the drug benzphetamine and the polycyclic hydrocarbon benzo {(alpha)} pyrene by tumor microsomes were inducible 2 to 3-fold and 2-fold, respectively by pretreatment of rats with phenobarbital/hydrocortisone. Hepatoma 5123t.c.(h) microsomal hydroxylation activities were more inducible after these pretreatments than hepatoma 7288C.t.c. Two chemotherapeutic drugs (cyclophosphamide and isophosphamide) were shown to be mutagenic after activation by the tumor hemogenate with the TA100 strain of Salmonella typhimurium bacteria. NADPH-cytochrome P-450 was purified from phenobarbital/hydrocortisone treated rat hepatoma 5123t.c.(H) microsomes 353-fold with a specific activity 63.6 nmol of cytochrome c reduced per min per mg of protein. The purified enzyme, has an apparent molecular weight of 79,500 daltons, and contained an equal molar ratio of FMN and FAD, with a total flavin content of 16.4 nmol per mg of protein. The purified enzyme also catalyzed electron transfer to artificial electron acceptors with the K(,m) values of the hepatoma reductase similar to those of purified liver reductase. The K(,m) value of the hepatoma reductase (13 uM) for NADPH was similar to that of purified liver reductase (5.0 uM). In addition the purified hepatoma reductase was immunochemically similar to the liver reductase.^ Hepatoma cytochrome P-450, the hemeprotein component of the hepatoma microsomes of rats pretreated with phenobarbital/hydrocortisone. The resolution of the six forms was achieved by the DE-53 ion-exchange chromatography, and further purified by hydroxyapatite. The six different fractions that contained P-450 activity, had specific contents from 0.47 to 1.75 nmol of cytochrome P-450 per mg of protein, and indicated a 2 to 9-fold purification as compared to the original microsomes. In addition, difference spectra, molecular weights and immunological results suggest there are at least six different forms of cytochrome P-450 in hepatoma 5123 t.c.(H). ^

A study of nurses' perceptions of and participation in the resolution of treatment dilemmas for critically ill newborns

This study was an exploratory investigation of variables which are associated with neonatal intensive care nurses' perceptions of and participation in life-sustaining treatment decisions for critically ill newborns. The primary purpose of the research was to examine the extent to which assessment of infants' physical and mental prognoses, parents' preferences regarding treatment, and legal consequences of non-treatment influence nurses' recommendations about life-saving treatment decisions for handicapped newborns. Secondly, the research explored the extent and nature of nurses' reported participation in the resolution of treatment dilemmas for these critically ill newborns. The framework of the study draws upon the work of Crane (1977), Blum (1980), and Pearlman (1982) who have explored the sociological context of decision-making with critical care patients.^ Participants in the study were a volunteer sample of eighty-three registered nurses who were currently working in neonatal intensive care units in five large urban hospitals in Texas. Data were collected through the use of intensive interviews and case study questionnaires. Results from the study indicate that physical and mental prognoses as well as parent preferences and concerns about legal liability are related to nurses' treatment recommendations, but their levels of significance vary according to the type of handicapping condition and whether the treatment questions are posed in terms of initiating aggressive therapy or withdrawing aggressive therapy.^ The majority of nurses reported that the extent of their participation in formal decision-making regarding handicapped newborns was fairly minimal although they provide much of the definitive data used to make decisions by physicians and parents. There was substantial evidence that nurse respondents perceive their primary role as advocates for critically ill newborns, and believe that their involvement in the resolution of treatment dilemmas should be increased. ^