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News Article | February 20, 2013
Site: www.businessinsider.com

New York City is continuing to make its mark in the startup community. In the last year, big-name companies spent $8.3 billion on mergers and acquisition deals in 100 New York-based startups, according to a recent report by PrivCo. That tally put New York right behind the heart of the tech industry, Silicon Valley, where 226 deals totaled $21.5 billion. After speaking with VCs and entrepreneurs, and scoping out AngelList, we selected 25 early stage startups that are generating a lot of buzz in the tech community.

Shubin N.J.,University of Rhode Island | Monaghan S.F.,University of Rhode Island | Ayala A.,University of Rhode Island | Ayala A.,Surgical Research
Contributions to Microbiology | Year: 2011

Over the past two decades, it has become well accepted that sepsis exhibits two, oftentimes concomitant, inflammatory stages; a pro-inflammatory phase, referred to as the systemic inflammatory response syndrome (SIRS), and an anti-inflammatory phase, called the compensatory anti-inflammatory response syndrome (CARS). Considering that therapeutic interventions designed to attenuate the pro-inflammatory septic response have generally failed, much recent research has gone into understanding how and why septic patients display immunosuppressive characteristics, what the significance of septic immunosuppression may be and if there exists any therapeutic targets within the CARS. Herein, we describe the potential mechanisms of the immunosuppressive/CARS phase of sepsis by discussing what anti-inflammatory agents, receptors and cell populations are currently believed to contribute to CARS. Copyright © 2011 S. Karger AG, Basel. Source

Dehne N.,Goethe University Frankfurt | Kerkweg U.,Institute of Physiological Chemistry | Flohe S.B.,Surgical Research | Brune B.,Goethe University Frankfurt | Fandrey J.,University of Duisburg - Essen
Shock | Year: 2011

Skeletal muscle damage provokes complex repair mechanisms including recruitment of leukocytes as well as activation of myogenic precursor cells such as satellite cells. To study muscle cell repair mechanisms after muscle fiber damage, we used an in vitro model of scrape-injured myotubes. Exposing vital C2C12 myoblasts and myotubes to cell debris of damaged myotubes revealed mRNA upregulation of adrenomedullin (ADM), insulin-like growth factors 1 and 2, metallopeptidase 9, and monocyte chemoattractant protein11. When cell debris was treated with ultrasound, frozen in liquid nitrogen, or heat inactivated before addition to C2C12 cells, gene expression was drastically reduced or completely absent. Moreover, incubations of myoblasts with debris separated by transwell inserts indicated that direct cell contact is required for gene induction. Incubation with albumin and PolyIC ruled out that ADM induction by cell debris simply results from increased protein or nucleic acid concentrations in the supernatant. Because the genes, which were upregulated by cell debris, are potential target genes of hypoxia-inducible factor (HIF), cells were analyzed for HIF-1α expression. Western blot analysis showed accumulation of the α-subunit upon contact to cell debris. Knockdown of HIF-1α in C2C12 cells proved that activation of HIF-1 in response to cell debris was responsible for upregulating ADM and monocyte chemoattractant protein 1. Furthermore, by incubating cells on gas-permeable culture dishes, we excluded a reduced pericellular pO2 induced by cell debris as the cause for ADM upregulation. Our data suggest that damaged myofibers activate HIF-1 in neighboring myotubes and precursor myoblasts by direct contact, concomitantly upregulating factors necessary for angiogenesis, tissue regeneration, and phagocyte recruitment. Copyright © 2011 by the Shock Society. Source

Guo Y.,University of Pittsburgh | Guo Y.,Shanghai JiaoTong University | Hu B.,University of Pittsburgh | Hu B.,Sun Yat Sen University | And 10 more authors.
Journal of Biological Chemistry | Year: 2015

Estrogen sulfotransferase (EST) regulates estrogen homeostasis by sulfonating and deactivating estrogens. Liver ischemia and reperfusion (I/R) involves both hypoxia during the ischemic phase and oxidative damage during the reperfusion phase. In this report, we showed that the expression of EST was markedly induced by I/R. Mechanistically, oxidative stress-induced activation of Nrf2 was responsible for the EST induction, which was abolished in Nrf2-/- mice. EST is a direct transcriptional target of Nrf2. In female mice, the I/R-responsive induction of EST compromised estrogen activity. EST ablation attenuated I/R injury as a result of decreased estrogen deprivation, whereas this benefit was abolished upon ovariectomy. The effect of EST ablation was sex-specific because the EST-/- males showed heightened I/R injury. Reciprocally, both estrogens and EST regulate the expression and activity of Nrf2. Estrogen deprivation by ovariectomy abolished the I/R-responsive Nrf2 accumulation, whereas the compromised estrogen deprivation in EST-/- mice was associated with increased Nrf2 accumulation. Our results suggested a novel I/R-responsive feedback mechanism to limit the activity of Nrf2 in which Nrf2 induces the expression of EST, which subsequently increases estrogen deactivation and limits the estrogen-responsive activation of Nrf2. Inhibition of EST, at least in females, may represent an effective approach to manage hepatic I/R injury. Source

Sun Q.,University of Pittsburgh | Gao W.,University of Pittsburgh | Loughran P.,University of Pittsburgh | Shapiro R.,University of Pittsburgh | And 4 more authors.
Journal of Biological Chemistry | Year: 2013

Caspase 1 activation can be induced by oxidative stress, which leads to the release of the proinflammatory cytokines IL1β and IL18 in myeloid cells and a potentially damaging inflammatory response. However, little is known about the role of caspase 1 in non-immune cells, such as hepatocytes, that express and activate the inflammasome but do not produce a significant amount of IL1β/IL18. Here we demonstrate that caspase 1 activation protects against cell death after redox stress induced by hypoxia/reoxygenation in hepatocytes. Mechanistically, we show that caspase 1 reduces mitochondrial respiration and reactive oxygen species by increasing mitochondrial autophagy and subsequent clearance of mitochondria in hepatocytes after hypoxia/reoxygenation. Caspase 1 increases autophagic flux through up-regulating autophagy initiator beclin 1 during redox stress and is an important cell survival factor in hepatocytes. We find that during hemorrhagic shock with resuscitation, an in vivo mouse model associated with severe hepatic redox stress, caspase 1 activation is also protective against liver injury and excessive oxidative stress through the up-regulation of beclin 1. Our findings suggest an alternative role for caspase 1 activation in promoting adaptive responses to oxidative stress and, more specifically, in limiting reactive oxygen species production and damage in cells and tissues where IL1β/IL18 are not highly expressed. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Source

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