Nitric oxide/Caveolin-1/MMP pathway: a novel therapeutic strategy for drug discovery from herbal medicine targeting blood-brain-barrier disruption during cerebral Ischemia-reperfusion injury

Symposium 1 - Permeability: no. S1-2AIMS: Blood-brain-barrier (BBB) disruption is a crucial process in stroke, but no effective drug is available. Thus, drug discovery targeting BBB permeability becomes timely important. In this study, we hypothesized that Nitric oxide (NO)/Cav-1/Matrix metalloproteinase (MMP) pathway is important therapeutic targets in preventing BBB disruption. Following, we investigated the effects of CG, an active compound isolated from Astragali Radix on regulating this pathway and protecting BBB permeability and brain damage during cerebral ischemia-reperfusion injury. METHODS: SD rats were subject to ...postprin

Planning with Information-Processing Constraints and Model Uncertainty in Markov Decision Processes

Information-theoretic principles for learning and acting have been proposed to solve particular classes of Markov Decision Problems. Mathematically, such approaches are governed by a variational free energy principle and allow solving MDP planning problems with information-processing constraints expressed in terms of a Kullback-Leibler divergence with respect to a reference distribution. Here we consider a generalization of such MDP planners by taking model uncertainty into account. As model uncertainty can also be formalized as an information-processing constraint, we can derive a unified solution from a single generalized variational principle. We provide a generalized value iteration scheme together with a convergence proof. As limit cases, this generalized scheme includes standard value iteration with a known model, Bayesian MDP planning, and robust planning. We demonstrate the benefits of this approach in a grid world simulation.Comment: 16 pages, 3 figure

Supernova Remnants as Clues to Their Progenitors

Supernovae shape the interstellar medium, chemically enrich their host galaxies, and generate powerful interstellar shocks that drive future generations of star formation. The shock produced by a supernova event acts as a type of time machine, probing the mass loss history of the progenitor system back to ages of $\sim$ 10 000 years before the explosion, whereas supernova remnants probe a much earlier stage of stellar evolution, interacting with material expelled during the progenitor's much earlier evolution. In this chapter we will review how observations of supernova remnants allow us to infer fundamental properties of the progenitor system. We will provide detailed examples of how bulk characteristics of a remnant, such as its chemical composition and dynamics, allow us to infer properties of the progenitor evolution. In the latter half of this chapter, we will show how this exercise may be extended from individual objects to SNR as classes of objects, and how there are clear bifurcations in the dynamics and spectral characteristics of core collapse and thermonuclear supernova remnants. We will finish the chapter by touching on recent advances in the modeling of massive stars, and the implications for observable properties of supernovae and their remnants.Comment: A chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin (18 pages, 6 figures

Harnessing Surface-Functionalized Metal-Organic Frameworks for Selective Tumor Cell Capture

A platform based on a metal-organic framework (MOF) bearing free carboxylic acid groups has been developed for tumor cell capture and potential drug screening applications. A zinc-based MOF expressing uncoordinated carboxylic acids (ZnMOF-COOH) was grown on a ZnO substrate. Post-synthetic modification (PSM) of the acid groups gave a composite material that expressed peptide linkages and allowed the immobilization of anti-epithelial cell adhesion molecule (anti-EpCAM) antibody. This strategy offers a universal method for the controllable immobilization of antibodies and even enzymes on the surface of a MOF. The resulting immunotrapper exhibited excellent capture ability, demonstrating high efficiency and selectivity towards EpCAM-positive tumor cells. The promotion of tumor cell adhesion is attributed to the 3-dimentional (3D) structure of the composite, which revealed spine-like microstructures.This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 21527809 and 21575007), the China Scholarship Council and the UK EPSRC (EP/J500380/1)

Overdiagnosis in breast cancer screening: the importance of length of observation period and lead time

PMCID: PMC3706885This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Solvothermal Synthesis of Ternary Sulfides of Sb2 − xBixS3(x = 0.4, 1) with 3D Flower-Like Architectures

Flower-like nanostructures of Sb2 − xBixS3(x = 0.4, 1.0) were successfully prepared using both antimony diethyldithiocarbamate [Sb(DDTC)3] and bismuth diethyldithiocarbamate [Bi(DDTC)3] as precursors under solvothermal conditions at 180 °C. The prepared Sb2 − xBixS3 with flower-like 3D architectures were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), high-resolution transmission electron microscopy (HRTEM), and selected area electron diffraction (SAED). The flower-like architectures, with an average diameter of ~4 μm, were composed of single-crystalline nanorods with orthorhombic structures. The optical absorption properties of the Sb2 − xBixS3 nanostructures were investigated by UV–Visible spectroscopy, and the results indicate that the Sb2 − xBixS3 compounds are semiconducting with direct band gaps of 1.32 and 1.30 eV for x = 0.4 and 1.0, respectively. On the basis of the experimental results, a possible growth mechanism for the flower-like Sb2 − xBixS3 nanostructures is suggested

Biological diversification linked to environmental stabilization following the Sturtian Snowball glaciation

The body fossil and biomarker records hint at an increase in biotic complexity between the two Cryogenian Snowball Earth episodes (ca. 661 million to ≤650 million years ago). Oxygen and nutrient availability can promote biotic complexity, but nutrient (particularly phosphorus) and redox dynamics across this interval remain poorly understood. Here, we present high-resolution paleoredox and phosphorus phase association data from multiple globally distributed drill core records through the non-glacial interval. These data are first correlated regionally by litho- and chemostratigraphy, and then calibrated within a series of global chronostratigraphic frameworks. The combined data show that regional differences in postglacial redox stabilization were partly controlled by the intensity of phosphorus recycling from marine sediments. The apparent increase in biotic complexity followed a global transition to more stable and less reducing conditions in shallow to mid-depth marine environments and occurred within a tolerable climatic window during progressive cooling after post-Snowball super-greenhouse conditions

Acclimation of methane emissions from rice paddy fields to straw addition

This is the final version. Available on open access from AAAS via the DOI in this recordData and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.Straw incorporation is a common long-term practice to improve soil fertility in croplands worldwide. However, straw amendments often increase methane (CH4) emissions from rice paddies, one of the main sources of anthropogenic CH4. Intergovernmental Panel on Climate Change (IPCC) methodologies to estimate CH4 emissions from rice agriculture assume that the effect of straw addition remains constant over time. Here, we show through a series of experiments and meta-analysis that these CH4 emissions acclimate. Effects of long-term (>5 years) straw application on CH4 emissions were, on average, 48% lower than IPCC estimates. Long-term straw incorporation increased soil methanotrophic abundance and rice root size, suggesting an increase in CH4 oxidation rates through improved O2 transport into the rhizosphere. Our results suggest that recent model projections may have overestimated CH4 emissions from rice agriculture and that CH4 emission estimates can be improved by considering the duration of straw incorporation and other management practices.National Key Research and Development Program of ChinaSpecial Fund for Agro-scientific Research in the Public InterestChina Agriculture Research System–Green ManureCentral Public-interest Scientific Institution Basal Research Fund of Institute of Crop ScienceInnovation Program of CAASGEF Project of Climate Smart Staple Crop Production in Chin

Adaptive Evolution of the Myo6 Gene in Old World Fruit Bats (Family: Pteropodidae)

PMCID: PMC3631194This 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

Deficiency and Also Transgenic Overexpression of Timp-3 Both Lead to Compromised Bone Mass and Architecture In Vivo

Tissue inhibitor of metalloproteinases-3 (TIMP-3) regulates extracellular matrix via its inhibition of matrix metalloproteinases and membrane-bound sheddases. Timp-3 is expressed at multiple sites of extensive tissue remodelling. This extends to bone where its role, however, remains largely unresolved. In this study, we have used Micro-CT to assess bone mass and architecture, histological and histochemical evaluation to characterise the skeletal phenotype of Timp-3 KO mice and have complemented this by also examining similar indices in mice harbouring a Timp-3 transgene driven via a Col-2a-driven promoter to specifically target overexpression to chondrocytes. Our data show that Timp-3 deficiency compromises tibial bone mass and structure in both cortical and trabecular compartments, with corresponding increases in osteoclasts. Transgenic overexpression also generates defects in tibial structure predominantly in the cortical bone along the entire shaft without significant increases in osteoclasts. These alterations in cortical mass significantly compromise predicted tibial load-bearing resistance to torsion in both genotypes. Neither Timp-3 KO nor transgenic mouse growth plates are significantly affected. The impact of Timp-3 deficiency and of transgenic overexpression extends to produce modification in craniofacial bones of both endochondral and intramembranous origins. These data indicate that the levels of Timp-3 are crucial in the attainment of functionally-appropriate bone mass and architecture and that this arises from chondrogenic and osteogenic lineages