Induction of apoptosis and activation of NF-kappaB by CD95 require different signalling thresholds

Mutations in the death domain of the death receptor CD95 (APO-1/Fas) cause lymphoproliferation and autoimmune disease in both lpr(cg) mice and in patients with autoimmune lymphoproliferative syndrome (ALPS) type Ia. By testing lymphocytes from ALPS type Ia patients, comparing heterozygous with homozygous lpr(cg) mice and coexpressing wild-type and mutant CD95 receptors, we demonstrate that induction of apoptosis requires two wild-type alleles of CD95. By contrast, nuclear factor-kappaB (NF-kappaB) can be fully activated in cells expressing both a mutant and a wild-type CD95 allele, suggesting different thresholds to activate the two signalling pathways. This was confirmed by testing lymphocytes from heterozygous lpr mice, which showed reduced sensitivity to CD95-mediated apoptosis but normal activation of NF-kappaB when compared with wild-type mice. Mutations in CD95 may eliminate the tumour-suppressive function of CD95, at the same time allowing induction of survival or proliferative pathways, which could contribute to the increased risk for lymphoma seen in ALPS type Ia patients.     

Molecular Imaging Reveals a Progressive Pulmonary Inflammation in Lower Airways in Ferrets Infected with 2009 H1N1 Pandemic Influenza Virus

Molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics. Herein we used [¹⁸F]-2-deoxy-2-fluoro-D-glucose ([¹⁸F]-FDG) as a radiotracer for PET imaging coupled with CT (FDG-PET/CT) to gain insight into the spatiotemporal progression of the inflammatory response of ferrets infected with a clinical isolate of a pandemic influenza virus, H1N1 (H1N1pdm). The thoracic regions of mock- and H1N1pdm-infected ferrets were imaged prior to infection and at 1, 2, 3 and 6 days post-infection (DPI). On 1 DPI, FDG-PET/CT imaging revealed areas of consolidation in the right caudal lobe which corresponded with elevated [¹⁸F]-FDG uptake (maximum standardized uptake values (SUVMax), 4.7–7.0). By days 2 and 3, consolidation (CT) and inflammation ([¹⁸F]-FDG) appeared in the left caudal lobe. By 6 DPI, CT images showed extensive areas of patchy ground-glass opacities (GGO) and consolidations with the largest lesions having high SUVMax (6.0–7.6). Viral shedding and replication were detected in most nasal, throat and rectal swabs and nasal turbinates and lungs on 1, 2 and 3 DPI, but not on day 7, respectively. In conclusion, molecular imaging of infected ferrets revealed a progressive consolidation on CT with corresponding [¹⁸F]-FDG uptake. Strong positive correlations were measured between SUVMax and bronchiolitis-related pathologic scoring (Spearman’s ρ = 0.75). Importantly, the extensive areas of patchy GGO and consolidation seen on CT in the ferret model at 6 DPI are similar to that reported for human H1N1pdm infections. In summary, these first molecular imaging studies of lower respiratory infection with H1N1pdm show that FDG-PET can give insight into the spatiotemporal progression of the inflammation in real-time.     

Inferring Gene Regulatory Networks by Singular Value Decomposition and Gravitation Field Algorithm

Reconstruction of gene regulatory networks (GRNs) is of utmost interest and has become a challenge computational problem in system biology. However, every existing inference algorithm from gene expression profiles has its own advantages and disadvantages. In particular, the effectiveness and efficiency of every previous algorithm is not high enough. In this work, we proposed a novel inference algorithm from gene expression data based on differential equation model. In this algorithm, two methods were included for inferring GRNs. Before reconstructing GRNs, singular value decomposition method was used to decompose gene expression data, determine the algorithm solution space, and get all candidate solutions of GRNs. In these generated family of candidate solutions, gravitation field algorithm was modified to infer GRNs, used to optimize the criteria of differential equation model, and search the best network structure result. The proposed algorithm is validated on both the simulated scale-free network and real benchmark gene regulatory network in networks database. Both the Bayesian method and the traditional differential equation model were also used to infer GRNs, and the results were used to compare with the proposed algorithm in our work. And genetic algorithm and simulated annealing were also used to evaluate gravitation field algorithm. The cross-validation results confirmed the effectiveness of our algorithm, which outperforms significantly other previous algorithms.     

Chemical composition and antidiabetic activity of Opuntia Milpa Alta extracts

Three new compounds, 1 – 3 , and 20 known compounds were isolated from the AcOEt and BuOH extract of edible Opuntia Milpa Alta. The petroleum ether extract was examined by GC and MS. A total of 26 compounds were identified, representing 95.6% of the total extract, phytosterol (36.03%) being the most abundant component, and polyunsaturated fatty acids (18.57%) represented the second largest group, followed by phytol (12.28%), palmitic acid, palmitate (13.54%), vitamin E (4.51%), and other compounds (7.47%). The effects of various extracts from edible Opuntia Milpa Alta (petroleum ether extract, AcOEt extract, BuOH extract, aqueous extract, H₂O parts) and the positive control (received dimethylbiguanide) were tested on streptozotocin (STZ)‐induced diabetic mice. The results indicated that all the treatment groups could significantly decrease blood glucose levels in STZ‐induced diabetic mice compared to the model control group (P<0.01), except the aqueous extract group (P<0.05). Especially, the petroleum ether extract group and the positive control group showed remarkable decrease of blood glucose levels. Taken together, the results indicate that the petroleum ether extract is the major hypoglycemic part in edible Opuntia Milpa Alta, which may be developed to a potential natural hypoglycemic functional ingredient.     

Differences in metabolite profile between blood plasma and serum

In metabolomic research, blood plasma and serum have been considered to possess similar compositions and properties. Their perceived equivalence has resulted in researchers choosing arbitrarily between serum and plasma for analysis. Here, routine serum and plasma were prepared and their low-molecular-weight compounds were determined using gas chromatography/time-of-flight mass spectrometry. Principal components analysis was applied to process the acquired data, and marked differences in metabolite profiles were observed between serum and plasma. Of the 72 identified compounds, 36 (50%) discriminate serum from plasma, with 29 and 7 metabolites showing a significantly higher abundance (t test, P < 0.05) in serum and plasma, respectively. Incubation of blood had distinct effects on the analyte peak areas, with the effects being more pronounced for plasma than for serum and more pronounced for a shorter incubation than for a longer incubation. These results highlight the importance in choosing serum or plasma as the analytical sample and in stipulating the incubation time. Because incubation affected the analyte peak areas less in serum than in plasma, we recommend serum as the sample of choice in metabolomic studies.     

In Situ TEM Study of Volume Expansion in Porous Carbon Nanofiber/Sulfur Cathodes with Exceptional High‐Rate Performance

Although lithium sulfur batteries (LSBs) have attracted much interest owing to their high energy densities, synthesis of high‐rate cathodes and understanding their volume expansion behavior still remain challenging. Herein, electrospinning is used to prepare porous carbon nanofiber (PCNF) hosts, where both the pore volume and surface area are tailored by optimizing the sacrificial agent content and the activation temperature. Benefiting from the ameliorating functional features of high electrical conductivity, large pore volume, and Li ion permselective micropores, the PCNF/A550/S electrode activated at 550 °C exhibits a high sulfur loading of 71 wt%, a high capacity of 945 mA h g^?1 at 1 C, and excellent high‐rate capability. The in situ transmission electron microscope examination reveals that the lithiation product, Li₂S, is contained within the electrode with only ≈35% volume expansion and the carbon host remains intact without fracture. In contrast, the PCNF/A750/S electrode with damaged carbon spheres exhibits sulfur sublimation, a larger volume expansion of over 61%, and overflowing of Li₂S, a testament to its poor cyclic stability. These findings provide, for the first time, a new insight into the correlation between volume expansion and electrochemical performance of the electrode, offering a potential design strategy to synthesize high‐rate and stable LSB cathodes.     

Stretchable Lithium‐Ion Batteries Enabled by Device‐Scaled Wavy Structure and Elastic‐Sticky Separator

Fast developments and substantial achievements have been shaping the field of wearable electronic devices, resulting in the persistent requirement for stretchable lithium‐ion batteries (LIBs). Despite recent progress in stretchable electrodes, stretching full batteries, including electrodes, separator, and sealing material, remains a great challenge. Here, a simple design concept for stretchable LIBs via a wavy structure at the full battery device scale is reported. All components including the package are capable of being reversibly stretched by folding the entire pouch cell into a wavy shape with polydimethylsiloxane filled in each valley region. In addition, the stretchable, sticky, and porous polyurethane/poly(vinylidene fluoride) membrane is adopted as a separator for the first time, which can maintain intimate contact between electrodes and separator to continuously secure ion pathway under dynamic state. Commercial cathode, anode, and package can be utilized in this rationally designed wavy battery to enable stretchability. The results indicate good electrochemical performances and long‐term stability at repeatable release–stretch cycles. A high areal capacity of 3.6 mA h cm^?2 and energy density of up to 172 W h L^?1 can be achieved for the wavy battery. The promising results of the cost‐effective wavy battery with high stretchability shed light on the development of stretchable energy storages.     

The configuration,solvatochromism and metallo‐responses of two novel cyano‐containing oligo(phenylene‐vinylene) derivatives

Two novel cyano‐containing oligo(phenylenevinylene) (OPV) derivatives have been designed and synthesized. Photophysical and sensing properties of the two compounds were studied. Such studies reveal the intramolecular charge transfer process between cyano groups and OPV core. The results showed that the alkyl difference of substituted OPV leads to the changes of molecular configuration and metallo‐response of two compounds. Copyright © 2010 John Wiley & Sons, Ltd.