The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.

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This paper establishes six stylized facts about firms' export prices using detailed customs data on the universe of Chinese trade flows. First, across firms selling a given product, exporters that charge higher prices earn greater revenues in each destination, have bigger worldwide sales, and enter more markets. Second, firms that export more, that enter more markets and that charge higher export prices import more expensive inputs. Third, across destinations within a firm-product, firms set higher prices in richer, larger, bilaterally more distant and overall less remote countries. Fourth, across destinations within a firm-product, firms earn bigger revenues in markets where they set higher prices. Fifth, across firms within a product, exporters with more destinations offer a wider range of export prices. Finally, firms that export more, that enter more markets and that offer a wider range of export prices pay a wider range of input prices and source inputs from more origin countries. We propose that trade models should incorporate two features to rationalize these patterns in the data: more successful exporters use higher-quality inputs to produce higher-quality goods (stylized facts 1 and 2), and firms vary the quality of their products across destinations by using inputs of different quality levels (stylized facts 3, 4, 5 and 6).

KIM-1 (kidney injury molecule-1) is a type I transmembrane glycoprotein expressed on dedifferentiated renal proximal tubule epithelial cells undergoing regeneration after toxic or ischemic injury. The extracellular domain of KIM-1 is composed of an immunoglobulin-like domain topping a long mucin-like domain, a structure that points to a possible role in cell adhesion by homology to several known adhesion proteins. Two splice variants (a and b), of the human KIM-1 having identical extracellular domains, differ in their cytoplasmic domains and tissue distributions. In this study, we report that the KIM-1b transcript is expressed predominantly in adult human kidney. We describe the generation of 10 monoclonal antibodies against the extracellular domain of human KIM-1, the mapping of their binding sites, and their use in identifying various forms of the protein. We show that human KIM-1b is expressed in adult kidney cell lines, and we demonstrate that a soluble form of KIM-1 is shed constitutively into the culture medium of the cell lines expressing endogenous or recombinant KIM-1b by membrane-proximal cleavage. A monoclonal antibody that binds at or close to the proteolytic site can partially block the shedding of KIM-1. Release of soluble KIM-1 is enhanced by activating the cells with phorbol 12-myristate 13-acetate and can be inhibited with two metalloproteinase inhibitors, BB-94 (Batimastat) and GM6001 (Ilomastat), suggesting that the cleavage is mediated by a metalloproteinase. We propose that the shedding of KIM-1 in the kidney undergoing regeneration constitutes an active mechanism allowing dedifferentiated regenerating cells to scatter on denuded patches of the basement membrane and reconstitute a continuous epithelial layer.

Abstract. This paper provides firm-level evidence that credit constraints restrict international trade flows and affect the pattern of foreign direct investment. Using detailed data from China, we show that foreign-owned firms and joint ventures have better export performance than private domestic firms, and this advantage is systematically greater in sectors at higher levels of financial vulnerability measured in a variety of ways. This confirms that financial frictions restrict international trade and is consistent with foreign affiliates being less credit constrained because they can tap internal funding from their parent company. Our results imply that FDI can compensate for domestic financial market imperfections and alleviate their impact on aggregate growth, trade and private sector development. Credit constraints and host-country financial institutions thus offer a new explanation for the sectoral and spatial composition of MNC activity. F10, F14, F23, F36, G32. JEL Classification codes:

Cisplatin is a widely used antineoplastic agent that has nephrotoxicity as a major side effect. The underlying mechanism of this nephrotoxicity is still not well known. Iron has been implicated to play an important role in several models of tissue injury, presumably through the generation of hydroxyl radicals via the Haber-Weiss reaction or other highly toxic free radicals. In the present study we examined the catalytic iron content and the effect of iron chelators in an in vitro model of cisplatin-induced cytotoxicity in LLC-PK1 cells (renal tubular epithelial cells) and in an in vivo model of cisplatin-induced acute renal failure in rats. Exposure of LLC-PK1 cells to cisplatin resulted in a significant increase in bleomycin-detectable iron (iron capable of catalyzing free radical reactions) released into the medium. Concurrent incubation of LLC-PK1 cells with iron chelators including deferoxamine and 1,10-phenanthroline significantly attenuated cisplatin-induced cytotoxicity as measured by lactate dehydrogenase (LDH) release. Bleomycin-detectable iron content was also markedly increased in the kidney of rats treated with cisplatin. Similarly, administration of deferoxamine in rats provided marked functional (as measured by blood urea nitrogen and creatinine) and histological protection against cisplatin-induced acute renal failure. In a separate study, we examined the role of hydroxyl radical in cisplatin-induced nephrotoxicity. Incubation of LLC-PK1 cells with cisplatin caused an increase in hydroxyl radical formation. Hydroxyl radical scavengers, dimethyl sulfoxide, mannitol and benzoic acid, significantly reduced cisplatin-induced cytotoxicity and, treatment with dimethyl sulfoxide or dimethylthiourea provided significant protection against cisplatin-induced acute renal failure. Taken together, our data strongly support a critical role for iron in mediating tissue injury via hydroxyl radical (or a similar oxidant) in this model of nephrotoxicity.

Contrary to previous arguments for a sharp retention threshold for onset of treatment effects, we find smooth curves relating treatment duration to drug use improvements in methadone maintenance, out-patient non-methadone and long-term residential modalities. These relationships are effectively linear for durations typically observed in single treatment episodes, but unusually long retention in out-patient non-methadone and long-term residential units appear steadily less predictive of improvement.

Developing single-site catalysts featuring maximum atom utilization efficiency is urgently desired to improve oxidation-reduction efficiency and cycling capability of lithium-oxygen batteries. Here, we report a green method to synthesize isolated cobalt atoms embedded ultrathin nitrogen-rich carbon as a dual-catalyst for lithium-oxygen batteries. The achieved electrode with maximized exposed atomic active sites is beneficial for tailoring formation/decomposition mechanisms of uniformly distributed nano-sized lithium peroxide during oxygen reduction/evolution reactions due to abundant cobalt-nitrogen coordinate catalytic sites, thus demonstrating greatly enhanced redox kinetics and efficiently ameliorated over-potentials. Critically, theoretical simulations disclose that rich cobalt-nitrogen moieties as the driving force centers can drastically enhance the intrinsic affinity of intermediate species and thus fundamentally tune the evolution mechanism of the size and distribution of final lithium peroxide. In the lithium-oxygen battery, the electrode affords remarkably decreased charge/discharge polarization (0.40 V) and long-term cyclability (260 cycles at 400 mA g−1).