Glutathione increase by the n-butanoyl glutathione derivative (GSH-C4) inhibits viral replication and induces a predominant Th1 immune profile in old mice infected with influenza virus

During aging, glutathione (GSH) content declines and the immune system undergoes a deficiency in the induction of Th1 response. Reduced secretion of Th1 cytokines, which is associated with GSH depletion, could weaken the host defenses against viral infections. We first evaluated the concentration of GSH and cysteine in organs of old mice; then, the effect of the administration of the N-butanoyl GSH derivative (GSH-C4) on the response of aged mice infected with influenza A PR8/H1N1 virus was studied through the determination of GSH concentration in organs, lung viral titer, IgA and IgG1/IgG2a production and Th1/Th2 cytokine profile. Old mice had lower GSH than young mice in organs. Also the gene expression of endoplasmic reticulum (ER) stress markers involved in GSH metabolism and folding of proteins, i.e. Nrf2 and PDI, was reduced. Following infection, GSH content remained low and neither infection nor GSH-C4 treatment affected Nrf2 expression. In contrast, PDI expression was upregulated during infection and appeared counterbalanced by GSH-C4. Moreover, the treatment with GSH-C4 increased GSH content in organs, reduced viral replication and induced a predominant Th1 response. In conclusion, GSH-C4 treatment could be used in the elderly to contrast influenza virus infection by inducing immune response, in particular the Th1 profile

Ubiquitin-proteasome signaling in lung injury

Cell homeostasis requires precise coordination of cellular proteins function. Ubiquitination is a post-translational modification that modulates protein half-life and function and is tightly regulated by ubiquitin E3 ligases and deubiquitinating enzymes. Lung injury can progress to acute respiratory distress syndrome that is characterized by an inflammatory response and disruption of the alveolocapillary barrier resulting in alveolar edema accumulation and hypoxemia. Ubiquitination plays an important role in the pathobiology of acute lung injury as it regulates the proteins modulating the alveolocapillary barrier and the inflammatory response. Better understanding of the signaling pathways regulated by ubiquitination may lead to novel therapeutic approaches by targeting specific elements of the ubiquitination pathways.Fil: Magnani, Natalia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; Argentina. Northwestern University; Estados UnidosFil: Dada, Laura Andrea. Northwestern University; Estados UnidosFil: Sznajder, Jacob I.. Northwestern University; Estados Unido

Efficiency of transient transformation in tobacco protoplasts is independent of plasmid amount

An optimized protocol for the transient transformation of tobacco protoplasts mediated by polyethylene\u2013glycol (PEG) is here described. As expected, the quantitative b\u2013glucuronidase (Gus) activity driven by pCaMVGus was dependent on the amount of plasmid used. Nevertheless, we demonstrate by an immunodetection method that transformation efficiency did not depend on the amount of plasmid used but on the limitation imposed by cell competence. In fact, we obtained the same percentage of transformed cells (about 60%) using a wide range of plasmid concentrations (0.1\u201310 mg per test). Finally, we show that, when we used two plasmid types in a mixture at a concentration ranging from 0.1 to 10 mg for each, all transformed cells expressed proteins encoded by both plasmids. Transient expression and co-transformation experiments are routinely used methods and, probably, the major results from this work were assumed by many researchers in this field, but our data experimentally support this assumption

Asbestos and cancer: An overview of current trends in Europe.

This review assesses the contribution of occupational asbestos exposure to the occurrence of mesothelioma and lung cancer in Europe. Available information on national asbestos consumption, proportions of the population exposed, and exposure levels is summarized. Population-based studies from various European regions on occupational asbestos exposure, mesothelioma, and lung cancer are reviewed. Asbestos consumption in 1994 ranged, per capita, between 0. 004 kg in northern Europe and 2.4 kg in the former Soviet Union. Population surveys from northern Europe indicate that 15 to 30% of the male (and a few percent of the female) population has ever had occupational exposure to asbestos, mainly in construction (75% in Finland) or in shipyards. Studies on mesothelioma combining occupational history with biologic exposure indices indicate occupational asbestos exposure in 62 to 85% of the cases. Population attributable risks for lung cancer among males range between 2 and 50% for definite asbestos exposure. After exclusion of the most extreme values because of methodologic aspects, most of the remaining estimates are within the range of 10 to 20%. Estimates of women are lower. Extrapolation of the results to national figures would decrease the estimates. Norwegian estimates indicate that one-third of expected asbestos-related lung cancers might be avoided if former asbestos workers quit smoking. The combination of a current high asbestos consumption per capita, high exposure levels, and high underlying lung cancer rates in Central Europe and the former Soviet Union suggests that the lung cancers will arise from the smoking-asbestos interaction should be a major concern

Structural, electronic, and magnetic characteristics of Np_2Co_(17)

A previously unknown neptunium-transition-metal binary compound Np_2Co_(17) has been synthesized and characterized by means of powder x-ray diffraction, ^(237)Np Mössbauer spectroscopy, superconducting-quantum-interference-device magnetometry, and x-ray magnetic circular dichroism (XMCD). The compound crystallizes in a Th_2Ni_(17)-type hexagonal structure with room-temperature lattice parameters α=8.3107(1) Å and c=8.1058(1) Å. Magnetization curves indicate the occurrence of ferromagnetic order below T_C>350 K. Mössbauer spectra suggest a Np^(3+) oxidation state and give an ordered moment of μ_(Np)=1.57(4) μ_B and μ_(Np)=1.63(4) μ_B for the Np atoms located, respectively, at the 2b and 2d crystallographic positions of the P6_3/mmc space group. Combining these values with a sum-rule analysis of the XMCD spectra measured at the neptunium M_(4,5) absorption edges, one obtains the spin and orbital contributions to the site-averaged Np moment [μ_S=−1.88(9) μ_B, μ_L=3.48(9) μ_B]. The ratio between the expectation value of the magnetic-dipole moment and the spin magnetic moment (m_(md)/μS=+1.36) is positive as predicted for localized 5f electrons and lies between the values calculated in intermediate-coupling (IC) and jj approximations. The expectation value of the angular part of the spin-orbit-interaction operator is in excellent agreement with the IC estimate. The ordered moment averaged over the four inequivalent Co sites, as obtained from the saturation value of the magnetization, is μ_(Co)≃1.6 μ_B. The experimental results are discussed against the predictions of first-principles electronic-structure calculations based on the spin-polarized local-spin-density approximation plus the Hubbard interaction

Integration of remote-sensing based metrics and econometric models to assess the socio-economic contributions of carbon sequestration in unmanaged tropical dry forests

Carbon sequestration by forests is one of the vital ecosystem services regulating the global climate. Equally important are the socio-economic co-benefits of carbon sequestration, given their implications for designing policies focused on conservation or restoration of tropical forests. Much debate has been around how to account for, and maximize, the co-benefits of carbon sequestration. Prior research suggests that a better understanding of the spatial relationship between carbon sequestration potential and forest types and dynamics - as a function of geographical context and time - is needed to better estimate their socio-economic benefits. Hence, this paper uses the Tropical Dry Forests of Central and South America to propose a new approach to quantify carbon sequestration of this biome, and its efficiency, using time series of the Terra-MODIS satellite. Our estimations of carbon sequestration are then coupled with a benefit transfer approach to infer carbon sequestration's monetary cost. Results reveal that these tropical forests sequester an annual average of 22.3 ​± ​3.3 tCO2 ha-1 yr-1 or in total, 1.16 GtCO2. The associated social cost of carbon, calculated using three econometric models, ranges from USD 489 ​ha-1 ​yr-1 to USD 2828 ​ha-1 ​yr-1. These results can open new perspectives regarding the benefits of carbon sequestration against the costs of the negative impacts of climate change for national welfare accounts, their relevance for environmental policy-making, and the implementation or monitoring of carbon-based incentive programs (e.g., WAVES)

Targeting Neutrophil Adhesive Events to Address Vaso-Occlusive Crisis in Sickle Cell Patients

Neutrophils are essential to protect the host against invading pathogens but can promote disease progression in sickle cell disease (SCD) by becoming adherent to inflamed microvascular networks in peripheral tissue throughout the body. During the inflammatory response, leukocytes extravasate from the bloodstream using selectin adhesion molecules and migrate to sites of tissue insult through activation of integrins that are essential for combating pathogens. However, during vaso-occlusion associated with SCD, neutrophils are activated during tethering and rolling on selectins upregulated on activated endothelium that line blood vessels. Recently, we reported that recognition of sLex on L-selectin by E-selectin during neutrophil rolling initiates shear force resistant catch-bonds that facilitate tethering to endothelium and activation of integrin bond clusters that anchor cells to the vessel wall. Evidence indicates that blocking this important signaling cascade prevents the congestion and ischemia in microvasculature that occurs from neutrophil capture of sickled red blood cells, which are normally deformable ellipses that flow easily through small blood vessels. Two recently completed clinical trials of therapies targeting selectins and their effect on neutrophil activation in small blood vessels reveal the importance of mechanoregulation that in health is an immune adaption facilitating rapid and proportional leukocyte adhesion, while sustaining tissue perfusion. We provide a timely perspective on the mechanism underlying vaso-occlusive crisis (VOC) with a focus on new drugs that target selectin mediated integrin adhesive bond formation

Accessing and assessing lunar resources with PROSPECT

PROSPECT is a package in development by ESA to assess the in-situ resource potential of lunar regolith. PROSPECT will: obtain sub-surface regolith samples, extract volatiles, identify chemical species, quantify abundances, and characterize isotopes

Subacute pericardial abscess after aortic valve replacement: a case report

BACKGROUND: Purulent pericarditis is an infectious disease, frequently caused by gram-positive bacteria, that is rarely observed in healthy individuals, and is often associated with predisposing conditions. CASE PRESENTATION: Here, we present the case of an Escherichia coli post-surgical localized purulent pericarditis complicated by transient constrictive pericarditis and its diagnostic and therapeutic management. CONCLUSIONS: Our case report focuses on the importance of imaging-guided treatment of purulent pericardial diseases, in particular on the emerging role of 18\u2009F-labelled 2-fluoro-2-deoxy-D-glucose Positron Emission Tomography/Computed Tomography in pericardial diseases and on the management of transient constrictive pericarditis, often seen after thoracic surgery