Murine model for Fusarium oxysporum invasive fusariosis reveals organ-specific structures for dissemination and long-term persistence

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Drought impact on forest carbon dynamics and fluxes in Amazonia

In 2005 and 2010 the Amazon basin experienced two strong droughts, driven by shifts in the tropical hydrological regime possibly associated with global climate change, as predicted by some global models. Tree mortality increased after the 2005 drought, and regional atmospheric inversion modelling showed basin-wide decreases in CO2 uptake in 2010 compared with 2011 (ref. 5). But the response of tropical forest carbon cycling to these droughts is not fully understood and there has been no detailed multi-site investigation in situ. Here we use several years of data from a network of thirteen 1-ha forest plots spread throughout South America, where each component of net primary production (NPP), autotrophic respiration and heterotrophic respiration is measured separately, to develop a better mechanistic understanding of the impact of the 2010 drought on the Amazon forest. We find that total NPP remained constant throughout the drought. However, towards the end of the drought, autotrophic respiration, especially in roots and stems, declined significantly compared with measurements in 2009 made in the absence of drought, with extended decreases in autotrophic respiration in the three driest plots. In the year after the drought, total NPP remained constant but the allocation of carbon shifted towards canopy NPP and away from fine-root NPP. Both leaf-level and plot-level measurements indicate that severe drought suppresses photosynthesis. Scaling these measurements to the entire Amazon basin with rainfall data, we estimate that drought suppressed Amazon-wide photosynthesis in 2010 by 0.38 petagrams of carbon (0.23-0.53 petagrams of carbon). Overall, we find that during this drought, instead of reducing total NPP, trees prioritized growth by reducing autotrophic respiration that was unrelated to growth. This suggests that trees decrease investment in tissue maintenance and defence, in line with eco-evolutionary theories that trees are competitively disadvantaged in the absence of growth. We propose that weakened maintenance and defence investment may, in turn, cause the increase in post-drought tree mortality observed at our plots.Gordon and Betty Moore FoundationNatural Environment Research Council (NERC)EU FP7 Amazalert (282664) projectEU FP7GEOCARBON (283080) projectNational Council for Scientific and Technological Development (CNPq, Brazil)ARC - fellowship awardERC - Advanced Investigator AwardRoyal Society - Wolfson Research Merit AwardJackson FoundationJohn Fell Fun

Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure.

BackgroundIntra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well-established translational ovine model of intra-amniotic C. albicans infection. In addition, we tested whether these potential adverse outcomes of the fetal brain were improved in utero by antifungal treatment with fluconazole.MethodsPregnant ewes received an intra-amniotic injection of 10(7) colony-forming units C. albicans or saline (controls) at 3 or 5 days before preterm delivery at 0.8 of gestation (term ~ 150 days). Fetal intra-amniotic/intra-peritoneal injections of fluconazole or saline (controls) were administered 2 days after C. albicans exposure. Post mortem analyses for fungal burden, peripheral immune activation, neuroinflammation, and white matter/neuronal injury were performed to determine the effects of intra-amniotic C. albicans and fluconazole treatment.ResultsIntra-amniotic exposure to C. albicans caused a severe systemic inflammatory response, illustrated by a robust increase of plasma interleukin-6 concentrations. Cerebrospinal fluid cultures were positive for C. albicans in the majority of the 3-day C. albicans-exposed animals whereas no positive cultures were present in the 5-day C. albicans-exposed and fluconazole-treated animals. Although C. albicans was not detected in the brain parenchyma, a neuroinflammatory response in the hippocampus and white matter was seen which was characterized by increased microglial and astrocyte activation. These neuroinflammatory changes were accompanied by structural white matter injury. Intra-amniotic fluconazole reduced fetal mortality but did not attenuate neuroinflammation and white matter injury.ConclusionsIntra-amniotic C. albicans exposure provoked acute systemic and neuroinflammatory responses with concomitant white matter injury. Fluconazole treatment prevented systemic inflammation without attenuating cerebral inflammation and injury

Assessment of pain during rest and during activities in the postoperative period of cardiac surgery

OBJECTIVE: to assess the intensity and site of pain after Cardiac Surgery through sternotomy during rest and while performing five activities. METHOD: descriptive study with a prospective cohort design. A total of 48 individuals participated in the study. A Multidimensional Scale for Pain Assessment was used. RESULTS: postoperative pain from cardiac surgery was moderate during rest and decreased over time. Pain was also moderate during activities performed on the 1st and 2nd postoperative days and decreased from the 3rd postoperative day, with the exception of coughing, which diminished only on the 6th postoperative day. Coughing, turning over, deep breathing and rest are presented in decreased order of intensity. The region of the sternum was the most frequently reported site of pain. CONCLUSION: the assessment of pain in the individuals who underwent cardiac surgery during rest and during activities is extremely important to adapt management and avoid postoperative complications and delayed surgical recovery

Expression-Based In Silico Screening of Candidate Therapeutic Compounds for Lung Adenocarcinoma

BACKGROUND:Lung adenocarcinom (AC) is the most common form of lung cancer. Currently, the number of medical options to deal with lung cancer is very limited. In this study, we aimed to investigate potential therapeutic compounds for lung adenocarcinoma based on integrative analysis. METHODOLOGY/PRINCIPAL FINDINGS:The candidate therapeutic compounds were identified in a two-step process. First, a meta-analysis of two published microarray data was conducted to obtain a list of 343 differentially expressed genes specific to lung AC. In the next step, expression profiles of these genes were used to query the Connectivity-Map (C-MAP) database to identify a list of compounds whose treatment reverse expression direction in various cancer cells. Several compounds in the categories of HSP90 inhibitor, HDAC inhibitor, PPAR agonist, PI3K inhibitor, passed our screening to be the leading candidates. On top of the list, three HSP90 inhibitors, i.e. 17-AAG (also known as tanespimycin), monorden, and alvespimycin, showed significant negative enrichment scores. Cytotoxicity as well as effects on cell cycle regulation and apoptosis were evaluated experimentally in lung adenocarcinoma cell line (A549 or GLC-82) with or without treatment with 17-AAG. In vitro study demonstrated that 17-AAG alone or in combination with cisplatin (DDP) can significantly inhibit lung adenocarcinoma cell growth by inducing cell cycle arrest and apoptosis. CONCLUSIONS/SIGNIFICANCE:We have used an in silico screening to identify compounds for treating lung cancer. One such compound 17-AAG demonstrated its anti-lung AC activity by inhibiting cell growth and promoting apoptosis and cell cycle arrest

Gemcitabine based combination chemotherapy in advanced pancreatic cancer-indirect comparison

<p>Abstract</p> <p>Background</p> <p>Recent meta-analyses have found a survival advantage with gemcitabine based combinations over single agent gemcitabine in patients with advanced pancreatic cancer. There is paucity of evidence in the form of direct head-to-head randomised controlled trials to determine which combinations are to be preferred.</p> <p>Method</p> <p>Using the adjusted indirect comparison method proposed by Bucher et al, we have assessed randomised controlled trials of four gemcitabine based combinations namely gemcitabine plus a platinum compound or 5-fluorouracil or irinotecan or capecitabine.</p> <p>Results</p> <p>No particular combination was significantly superior to another, but the indirect evidence suggests some important trends.</p> <p>Conclusion</p> <p>The strongest trends on indirect comparison are towards favouring gemcitabine plus capecitabine or gemcitabine plus a platinum compound over gemcitabine plus irinotecan, and to a lesser degree, over gemcitabine plus 5-fluorouracil.</p