In vivo Kinetic Biodistribution of Nano‐Sized Outer Membrane Vesicles Derived from Bacteria

Evaluation of kinetic distribution and behaviors of nanoparticles in vivo provides crucial clues into their roles in living organisms. Extracellular vesicles are evolutionary conserved nanoparticles, known to play important biological functions in intercellular, inter‐species, and inter‐kingdom communication. In this study, the first kinetic analysis of the biodistribution of outer membrane vesicles (OMVs)—bacterial extracellular vesicles—with immune‐modulatory functions is performed. OMVs, injected intraperitoneally, spread to the whole mouse body and accumulate in the liver, lung, spleen, and kidney within 3 h of administration. As an early systemic inflammation response, increased levels of TNF‐α and IL‐6 are observed in serum and bronchoalveolar lavage fluid. In addition, the number of leukocytes and platelets in the blood is decreased. OMVs and cytokine concentrations, as well as body temperature are gradually decreased 6 h after OMV injection, in concomitance with the formation of eye exudates, and of an increase in ICAM‐1 levels in the lung. Following OMV elimination, most of the inflammatory signs are reverted, 12 h post‐injection. However, leukocytes in bronchoalveolar lavage fluid are increased as a late reaction. Taken together, these results suggest that OMVs are effective mediators of long distance communication in vivo.     

Structural Cues for Understanding eEF1A2 Moonlighting

Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades.     

Are all cognitive therapies alike? A comparison of cognitive and noncognitive therapy process and implications for the application of empirically supported treatments.

The definition of an empirically supported treatment (EST) arguably embodies 2 untested assumptions: (a) that different manualized renditions of the same therapy are functionally equivalent and (b) that therapies can be reliably applied independently of therapist, setting, and format. These assumptions were tested as applied to cognitive therapy (CT), using process data from a large multisite study (N=235) that included 3 cognitive and 6 alternative therapies. Although the non-CTs were more variable than the CTs on 2 of 4 dimensions studied (directiveness and emotional arousal), there was considerable variation among the 3 CTs, even when implemented in the current context of rigorous training, manualization, and adherence checks. Results are discussed as related to the assumptions underlying EST criteria. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Static and Dynamic Spins in Superconducting La2−x Sr x CuO4: The Risø Years

One important area of modern condensed matter research is the investigation of the nature of the superconducting cuprates. Much progress in this field has been obtained with the technique of neutron scattering. We here present a review of neutron scattering studies of the high-temperature superconductor La_2?xSr_xCuO₄, performed at Risø National Laboratory. We review the work on the mapping of the incommensurate spin fluctuations, the investigation of the gap in the fluctuation spectrum, the magnetic properties of the vortices appearing in an applied field, and the quantum critical behaviour of the system. We discuss our findings in the light of results of neutron scattering from other groups, on other cuprate systems, and results from other experimental methods, e.g. NMR, μSR, STM, X-ray diffraction, and ARPES. We end with a discussion on the implications of the experimental results for the progress in the general understanding of high-temperature superconductivity. PACS numbers: 61.12.Ex, 74.20.Mn, 74.72.Dn, 75.25.+z, 78.70.Nx.     

A quadruple well, quadruple polysilicon BiCMOS process for fast 16Mb SRAM's

An advanced, high-performance, quadruple well, quadruple polysilicon BiCMOS technology has been developed for fast 16 Mb SRAM's. A split word-line bitcell architecture, using four levels of polysilicon and two self-aligned contacts, achieves a cell area of 8.61 μm² with conventional I-line lithography and 7.32 μm² with I-line plus phase-shift or with deep UV lithography. The process features PELOX isolation to provide a 1.0 μm active pitch, MOSFET transistors designed for a 0.80 μm gate poly pitch, a double polysilicon bipolar transistor with aggressively scaled parasitics, and a thin-film polysilicon transistor to enhance bitcell stability. A quadruple-well structure improves soft error rate (SER) and allows simultaneous optimization of MOSFET and bipolar performance     

Is there a role for continuation phase cognitive therapy for depressed outpatients?

Two pilot studies evaluated the rate of relapse or recurrence (i.e., major depressive disorder) after cognitive therapy (CT). Two sequential cohorts included outpatients who responded to acute phase CT (A-CT) and who agreed to monthly, treatment-free follow-up. In Study 1, the Kaplan-Meier technique estimated relapse and recurrence rates of 40% at 6 months, 45% at 8 months, 50% at 12 months, 67% at 18 months, and 74% at 24 months. In Study 2, responders to A-CT received 8 months (10 sessions) of continuation phase CT (C-CT). In Study 2, relapse or recurrence was 20% at 6 and 8 months, 27% at 12 months, and 36% at 18 and 24 months after A-CT. An exploratory log-rank test showed that relapse or recurrence-free survival was greater in Study 2 than in Study 1. If replicated, this result suggests that C-CT can reduce depressive relapse or recurrence. Alternative explanations are presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A CCG repeat polymorphism adjacent to the CAG repeat in the Huntington disease gene: implications for diagnostic accuracy and predictive testing

STUDY HYPOTHESIS: Concentrated aqueous solutions of hydroxocobalamin (OHCob) are given intravenously for the treatment of cyanide poisoning. Because OHCob solutions are intensely red and have peak light absorptions at 352 nm and 525 nm, we investigated whether the presence of OHCob in serum would interfere with various automated, colorimetric chemistry measurements. DESIGN: Selected serum chemistry colorimetric measurements were compared in seven patients, using their own serum as control, with serum containing OHCob at the following concentrations: 100 mg/L, 500 mg/L, and 1,000 mg/L. These concentrations are in the range achieved with therapeutic doses of OHCob when given for cyanide poisoning. MEASUREMENTS AND MAIN RESULTS: Statistically significant alterations in serum values for aspartate aminotransferase, total bilirubin, creatinine, magnesium, and iron were seen in the presence of OHCob. CONCLUSION: The presence of OHCob in serum interferes with several chemistry methodologies, and such interference should be anticipated when this antidote is used.     

In Vitro Characterization of Human CD24hiCD38hi Regulatory B Cells Shows CD9 Is Not a Stable Breg Cell Marker

Regulatory B (Breg) cells are endowed with immune suppressive functions. Various human and murine Breg subtypes have been reported. While interleukin (IL)-10 intracellular staining remains the most reliable way to identify Breg cells, this technique hinders further essential functional studies. Recent findings suggest that CD9 is an effective surface marker of murine IL-10 competent Breg cells. However, the stability of CD9 and its relevance as a unique marker for human Breg cells, which have been widely characterized as CD24^hiCD38^hi, have not been investigated. Here, we demonstrate that CD9 expression is sensitive to in vitro B cell stimulations. CD9 expression could either be re-expressed or downregulated in purified CD9-negative B cells and CD9-positive B cells, respectively. We found no significant differences in the Breg differentiation capacity of the CD9-negative and CD9-positive B cells. Furthermore, CD9-positive B cells co-express CD40 and CD86, suggesting their nature as B cell activation or co-stimulatory molecules, rather than regulatory ones. Therefore, we report the relatively unstable CD9 as a distinct surface molecule, indicating the need for further research for a more reliable marker to purify human Breg cells.     

CHARACTERIZATION OF EVA-BASED ADHESIVES CONTAINING DIFFERENT AMOUNTS OF ROSIN ESTER OR POLYTERPENE TACKIFIER

Different amounts (50-170 php--parts per hundred parts of EVA, 33-63 wt%) of two tackifiers (hydrogenated rosin ester, polyterpene resin) were added to an ethylene vinyl acetate (EVA) copolymer containing 28 wt% vinyl acetate. The EVA and the tackifier were characterized using infrared (IR) spectroscopy, DSC measurements, and stress-controlled plate-plate rheology. The properties and compatibility of the EVA-tackifier mixtures were studied using DSC, DMTA, and stress-controlled plate-plate rheology. Immediate adhesion was measured as a quantification of tack, and the T-peel strength of roughened styrene-butadiene rubber/EVA-tackifier adhesive joints was also obtained. The increase in the amount of tackifier noticeably changed the crystallinity of polyethylene blocks in the EVA, and the temperature at the cross-over between the curves of the storage and loss moduli as a function of the temperature was displaced to a lower value. Whereas the hydrogenated rosin ester was compatible with the amorphous ethylene vinyl acetate copolymer regions of the EVA (Tg value increased) reducing its crystallinity, the polyterpene resin was compatible with the polyethylene blocks of the EVA (T g value was not modified), increasing its crystallinity. Immediate adhesion of the EVA-tackifier mixtures was improved by adding both hydrogenated rosin ester and polyterpene tackifiers. On the other hand, there was an optimum tackifier content at which the maximum T-peel strength value was obtained.