Research frontiers for improving our understanding of drought-induced tree and forest mortality

Accumulating evidence highlights increased mortality risks for trees during severe drought, particularly under warmer temperatures and increasing vapour pressure deficit (VPD). Resulting forest die-off events have severe consequences for ecosystem services, biophysical and biogeochemical land–atmosphere processes. Despite advances in monitoring, modelling and experimental studies of the causes and consequences of tree death from individual tree to ecosystem and global scale, a general mechanistic understanding and realistic predictions of drought mortality under future climate conditions are still lacking. We update a global tree mortality map and present a roadmap to a more holistic understanding of forest mortality across scales. We highlight priority research frontiers that promote: (1) new avenues for research on key tree ecophysiological responses to drought; (2) scaling from the tree/plot level to the ecosystem and region; (3) improvements of mortality risk predictions based on both empirical and mechanistic insights; and (4) a global monitoring network of forest mortality. In light of recent and anticipated large forest die-off events such a research agenda is timely and needed to achieve scientific understanding for realistic predictions of drought-induced tree mortality. The implementation of a sustainable network will require support by stakeholders and political authorities at the international level

Fully spray-coated triple-cation perovskite solar cells

We use ultrasonic spray-coating to sequentially deposit thin films of tin oxide, a triple-cation perovskite and spiro-OMeTAD, allowing us fabricate perovskite solar cells (PSCs) with a champion reverse scan power conversion efficiency (PCE) of 19.4% on small-area substrates. We show that the use of spray-deposition permits us to rapidly (>80 mm s−1) coat 25 mm × 75 mm substrates that were divided into a series of devices each with an active area of 15.4 mm2, yielding an average PCE of 10.3% and a peak PCE of 16.3%. By connecting seven 15.4 mm2 devices in parallel on a single substrate, we create a device having an effective active area of 1.08 cm2 and a PCE of 12.7%. This work demonstrates the possibility for spray-coating to fabricate high efficiency and low-cost perovskite solar cells at speed

Rabies Situation in Cambodia

In Cambodia, rabies still elicits fear in the communities. Since 1998 the Institut Pasteur in Cambodia (IPC), Phnom Penh has been the only source of free post-exposure prophylaxis (PEP) and post mortem diagnosis. During 1998–2007, on average ∼12,400 patients received PEP annually at IPC (range 8,907–14,475) and 63 fatal human cases presenting with encephalitis following a dog bite were reported including 73% who tested positive by fluorescent-antibody test on brain samples or/and by reverse-transcriptase polymerase chain reaction on skin, cerebrospinal fluid, or urine. In 2007, 14,475 patients received PEP (100 PEP/100,000 people in Cambodia) including 95% who resided in Phnom Penh city (615 PEP/100,000) or five neighboring provinces. Using a step-by-step probability model, we estimated that 810 human rabies deaths would occur in 2007 (95% confidence interval [CI] 394–1,607); an incidence of 5.8/100,000 (95%CI 2.8–11.5). As a result, despite high attendance at the IPC's PEP center most Cambodians living in peripheral provinces in Cambodia may not have adequate access to PEP. Finally, the model generated one of the highest incidences of rabies worldwide. A national rabies control program is needed to improve surveillance and access to PEP, and to initiate vaccination campaigns in dogs

Hepatocyte Growth Factor Increases Osteopontin Expression in Human Osteoblasts through PI3K, Akt, c-Src, and AP-1 Signaling Pathway

BACKGROUND: Hepatocyte growth factor (HGF) has been demonstrated to stimulate osteoblast proliferation and participated bone remodeling. Osteopontin (OPN) is a secreted phosphoglycoprotein that belongs to the SIBLING family and is present during bone mineralization. However, the effects of HGF on OPN expression in human osteoblasts are large unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that HGF induced OPN expression in human osteoblasts dose-dependently. HGF-mediated OPN production was attenuated by c-Met inhibitor and siRNA. Pretreatment of osteoblasts with PI3K inhibitor (Ly294002), Akt inhibitor, c-Src inhibitor (PP2), or AP-1 inhibitor (curcumin) blocked the potentiating action of HGF. Stimulation of osteoblasts with HGF enhanced PI3K, Akt, and c-Src activation. In addition, incubation of cells with HGF also increased c-Jun phosphorylation, AP-1-luciferase activity, and c-Jun binding to the AP-1 element on the OPN promoter. HGF-mediated AP-1-luciferase activity and c-Jun binding to the AP-1 element was reduced by c-Met inhibitor, Ly294002, Akt inhibitor, and PP2. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the interaction between HGF and c-Met increases OPN expression in human osteoblasts via the PI3K, Akt, c-Src, c-Jun, and AP-1 signaling pathway

Epigenetic Silencing of IRF7 and/or IRF5 in Lung Cancer Cells Leads to Increased Sensitivity to Oncolytic Viruses

Defective IFN signaling results in loss of innate immunity and sensitizes cells to enhanced cytolytic killing after Vesticular Stomatitis Virus (VSV) infection. Examination of the innate immunity status of normal human bronchial epithelial cells Beas2B and 7 lung cancer cells revealed that the abrogation of IFN signaling in cancer cells is associated with greater sensitivity to VSV infection. The disruption of the IFN pathway in lung cancer cell lines and primary tumor tissues is caused by epigenetic silencing of critical interferon responsive transcription factors IRF7 and/or IRF5. Although 5-aza-2′-deoxycytidine treatment fails to reactivate IRF7 and IRF5 expression or protect cells from VSV infection, manipulating IFN signaling by altering IRF expression changes the viral susceptibility of these cells. Lung cancer cells can be partially protected from viral killing using IRF5+IRF7 overexpression, whereas IFN pathway disruption by transfection of siRNAs to IRF5+IRF7 increases cells' vulnerability to viral infection. Therefore, IRF5 and IRF7 are key transcription factors in IFN pathway that determine viral sensitivity of lung cancer cells; the epigenetically impaired IFN pathway in lung cancer tissues provides potential biomarkers for successful selective killing of cancer cells by oncolytic viral therapy

Cardiovascular Applications of Hyperpolarized MRI

Many applications of MRI are limited by an inherently low sensitivity. Previous attempts to overcome this insensitivity have focused on the use of MRI systems with stronger magnetic fields. However, the gains that can be achieved in this way are relatively small and increasing the magnetic field invariably leads to greater technical challenges. More recently, the development of a range of techniques, which can be gathered under the umbrella term of “hyperpolarization,” has offered potential solutions to the low sensitivity. Hyperpolarization techniques have been demonstrated to temporarily increase the signal available in an MRI experiment by as much as 100,000-fold. This article outlines the main hyperpolarization techniques that have been proposed and explains how they can increase MRI signals. With particular emphasis on the emerging technique of dynamic nuclear polarization, the existing preclinical cardiovascular applications are reviewed and the potential for clinical translation is discussed

Direct Binding of a Hepatitis C Virus Inhibitor to the Viral Capsid Protein

Over 130 million people are infected chronically with hepatitis C virus (HCV), which, together with HBV, is the leading cause of liver disease. Novel small molecule inhibitors of Hepatitis C virus (HCV) are needed to complement or replace current treatments based on pegylated interferon and ribavirin, which are only partially successful and plagued with side-effects. Assembly of the virion is initiated by the oligomerization of core, the capsid protein, followed by the interaction with NS5A and other HCV proteins. By screening for inhibitors of core dimerization, we previously discovered peptides and drug-like compounds that disrupt interactions between core and other HCV proteins, NS3 and NS5A, and block HCV production. Here we report that a biotinylated derivative of SL209, a prototype small molecule inhibitor of core dimerization (IC50 of 2.80 µM) that inhibits HCV production with an EC50 of 3.20 µM, is capable of penetrating HCV-infected cells and tracking with core. Interaction between the inhibitors, core and other viral proteins was demonstrated by SL209–mediated affinity-isolation of HCV proteins from lysates of infected cells, or of the corresponding recombinant HCV proteins. SL209-like inhibitors of HCV core may form the basis of novel treatments of Hepatitis C in combination with other target-specific HCV drugs such as inhibitors of the NS3 protease, the NS5B polymerase, or the NS5A regulatory protein. More generally, our work supports the hypothesis that inhibitors of viral capsid formation might constitute a new class of potent antiviral agents, as was recently also shown for HIV capsid inhibitors