711 research outputs found

    Spatial and Temporal Changes of Tidal Inlet Using Object-Based Image Analysis of Multibeam Echosounder Measurements: A Case from the Lagoon of Venice, Italy

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    Scientific exploration of seabed substrata has significantly progressed in the last few years. Hydroacoustic methods of seafloor investigation, including multibeam echosounder measurements, allow us to map large areas of the seabed with unprecedented precision. Through time-series of hydroacoustic measurements, it was possible to determine areas with distinct characteristics in the inlets of the Lagoon of Venice, Italy. Their temporal variability was investigated. Monitoring the changes was particularly relevant, considering the presence at the channel inlets of mobile barriers of the Experimental Electromechanical Module (MoSE) project installed to protect the historical city of Venice from flooding. The detection of temporal and spatial changes was performed by comparing seafloor maps created using object-based image analysis and supervised classifiers. The analysis included extraction of 25 multibeam echosounder bathymetry and backscatter features. Their importance was estimated using an objective approach with two feature selection methods. Moreover, the study investigated how the accuracy of classification could be affected by the scale of object-based segmentation. The application of the classification method at the proper scale allowed us to observe habitat changes in the tidal inlet of the Venice Lagoon, showing that the sediment substrates located in the Chioggia inlet were subjected to very dynamic changes. In general, during the study period, the area was enriched in mixed and muddy sediments and was depleted in sandy deposits. This study presents a unique methodological approach to predictive seabed sediment composition mapping and change detection in a very shallow marine environment. A consistent, repeatable, logical site-specific workflow was designed, whose main assumptions could be applied to other seabed mapping case studies in both shallow and deep marine environments, all over the world

    Therapeutic efficacy of favipiravir against Bourbon virus in mice

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    Bourbon virus (BRBV) is an emerging tick-borne RNA virus in the orthomyxoviridae family that was discovered in 2014. Although fatal human cases of BRBV have been described, little is known about its pathogenesis, and no antiviral therapies or vaccines exist. We obtained serum from a fatal case in 2017 and successfully recovered the second human infectious isolate of BRBV. Next-generation sequencing of the St. Louis isolate of BRBV (BRBV-STL) showed >99% nucleotide identity to the original reference isolate. Using BRBV-STL, we developed a small animal model to study BRBV-STL tropism in vivo and evaluated the prophylactic and therapeutic efficacy of the experimental antiviral drug favipiravir against BRBV-induced disease. Infection of Ifnar1-/- mice lacking the type I interferon receptor, but not congenic wild-type animals, resulted in uniformly fatal disease 6 to 10 days after infection. RNA in situ hybridization and viral yield assays demonstrated a broad tropism of BRBV-STL with highest levels detected in liver and spleen. In vitro replication and polymerase activity of BRBV-STL were inhibited by favipiravir. Moreover, administration of favipiravir as a prophylaxis or as post-exposure therapy three days after infection prevented BRBV-STL-induced mortality in immunocompromised Ifnar1-/- mice. These results suggest that favipiravir may be a candidate treatment for humans who become infected with BRBV

    Mn-based methacrylated gellan gum hydrogels for MRI-guided cell delivery and imaging

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    This work aims to engineer a new stable injectable Mn-based methacrylated gellan gum (Mn/GG-MA) hydrogel for real-time monitored cell delivery into the central nervous system. To enable the hydrogel visualization under Magnetic Resonance Imaging (MRI), GG-MA solutions were supplemented with paramagnetic Mn2+ ions before its ionic crosslink with artificial cerebrospinal fluid (aCSF). The resulting formulations were stable, detectable by T1-weighted MRI scans and also injectable. Cell-laden hydrogels were prepared using the Mn/GG-MA formulations, extruded into aCSF for crosslink, and after 7 days of culture, the encapsulated human adipose-derived stem cells remained viable, as assessed by Live/Dead assay. In vivo tests, using double mutant MBPshi/shi/rag2 immunocompromised mice, showed that the injection of Mn/GG-MA solutions resulted in a continuous and traceable hydrogel, visible on MRI scans. Summing up, the developed formulations are suitable for both non-invasive cell delivery techniques and image-guided neurointerventions, paving the way for new therapeutic procedures.Sílvia Vieira acknowledges the FCT Ph.D. scholarship (SFRH/BD/102710/2014). J. Miguel Oliveira and J. Silva-Correia acknowledge the FCT grants under the Investigator FCT program (IF/01285/2015 and IF/00115/2015, respectively). The authors also acknowledge the funds provided under the project NanoTech4ALS, funded under the EU FP7 M-ERA.NET program, and ESF (POWR.03.02.00-00-I028/17-00)

    The cultural antiquity of rainforests: Human-plant associations during the mid-late Holocene in the interior highlands of Sarawak, Malaysian Borneo

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    © 2015 Elsevier Ltd and INQUA. Rainforests are often described as the world's last virgin landscapes; however hunter-gatherers may have been modifying these environments for over 50,000 years. Despite this, the antiquity of early tropical forest exploitation by hunter-gathers and the transition to farming are still poorly understood. Today globalization drives deforestation of rainforests at an unprecedented rate. The forest, the lives of its present-day inhabitants, and the archaeological evidence for their history are unlikely to survive for much longer in their present form. The 'Cultured Rainforest Project', an interdisciplinary project involving anthropologists, archaeologists and palaeoecologists, was set up in 2007 to investigate the long-term and present-day interactions between people and the rainforest in the Kelabit Highlands of central Borneo, so as to better understand past and present agricultural and hunter-gatherer lifestyles and landscapes. This paper examines the environmental evidence used to investigate initial signs of plant exploitation and the transition to agriculture, as well as to understand the wider significance of past plants in a changing cultural landscape. Results have shown that two pronounced cultural waves of human-plant interactions took place in the Kelabit Highlands during the late Holocene; although tentative marks may be present on the landscape ca.7000-6000 years ago. The first pronounced wave of human-plant interaction begins from at least 3000 cal BP. It seems to correspond with the appearance of stone mounds and open-air sites recorded in the archaeological record. The sago palm Eugeissona plays an important role during this period. A second wave of cultural activity, particularly in the last 450 years, is recorded in the southern Kelabit Highlands and is marked by rice becoming important. This may be linked to the construction of a wide range of different megaliths and earthworks, due to its inferred association with wealth and status in prehistoric and historic periods. It is perhaps also linked to a rise in trade between the coastal regions and highlands

    RecA-mediated strand invasion of DNA by oligonucleotides substituted with 2-aminoadenine and 2-thiothymine

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    Sequence-specific recognition of DNA is a critical step in gene targeting. Here we describe unique oligonucleotide (ON) hybrids that can stably pair to both strands of a linear DNA target in a RecA-dependent reaction with ATP or ATPγS. One strand of the hybrids is a 30-mer DNA ON that contains a 15-nt-long A/T-rich central core. The core sequence, which is substituted with 2-aminoadenine and 2-thiothymine, is weakly hybridized to complementary locked nucleic acid or 2′-OMe RNA ONs that are also substituted with the same base analogs. Robust targeting reactions took place in the presence of ATPγS and generated metastable double D-loop joints. Since the hybrids had pseudocomplementary character, the component ONs hybridized less strongly to each other than to complementary target DNA sequences composed of regular bases. This difference in pairing strength promoted the formation of joints capable of accommodating a single mismatch. If similar joints can form in vivo, virtually any A/T-rich site in genomic DNA could be selectively targeted. By designing the constructs so that the DNA ON is mismatched to its complementary sequence in DNA, joint formation might allow the ON to function as a template for targeted point mutation and gene correction

    Small RNAs Targeting Transcription Start Site Induce Heparanase Silencing through Interference with Transcription Initiation in Human Cancer Cells

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    Heparanase (HPA), an endo-h-D-glucuronidase that cleaves the heparan sulfate chain of heparan sulfate proteoglycans, is overexpressed in majority of human cancers. Recent evidence suggests that small interfering RNA (siRNA) induces transcriptional gene silencing (TGS) in human cells. In this study, transfection of siRNA against −9/+10 bp (siH3), but not −174/−155 bp (siH1) or −134/−115 bp (siH2) region relative to transcription start site (TSS) locating at 101 bp upstream of the translation start site, resulted in TGS of heparanase in human prostate cancer, bladder cancer, and gastric cancer cells in a sequence-specific manner. Methylation-specific PCR and bisulfite sequencing revealed no DNA methylation of CpG islands within heparanase promoter in siH3-transfected cells. The TGS of heparanase did not involve changes of epigenetic markers histone H3 lysine 9 dimethylation (H3K9me2), histone H3 lysine 27 trimethylation (H3K27me3) or active chromatin marker acetylated histone H3 (AcH3). The regulation of alternative splicing was not involved in siH3-mediated TGS. Instead, siH3 interfered with transcription initiation via decreasing the binding of both RNA polymerase II and transcription factor II B (TFIIB), but not the binding of transcription factors Sp1 or early growth response 1, on the heparanase promoter. Moreover, Argonaute 1 and Argonaute 2 facilitated the decreased binding of RNA polymerase II and TFIIB on heparanase promoter, and were necessary in siH3-induced TGS of heparanase. Stable transfection of the short hairpin RNA construct targeting heparanase TSS (−9/+10 bp) into cancer cells, resulted in decreased proliferation, invasion, metastasis and angiogenesis of cancer cells in vitro and in athymic mice models. These results suggest that small RNAs targeting TSS can induce TGS of heparanase via interference with transcription initiation, and significantly suppress the tumor growth, invasion, metastasis and angiogenesis of cancer cells

    Childhood brain tumors: A review of strategies to translate CNS drug delivery to clinical trials

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    Brain tumors account for over 20% of childhood cancers and are the biggest cancer killer in children and young adults. Several initiatives over the past 40 years have tried to identify more effective drug treatments, but with very limited success. This is largely due to the bloodâ brain barrier, which restricts the entry of many drugs into the brain. In this review, we describe the main techniques that are being developed to enhance brain tumor drug delivery and explore the preclinical brain tumor models that are essential for translational development of these techniques. We also identify existing approved drugs that, if coupled with an efficient delivery method, could have potential as brain tumor treatments. Bringing this information together is part of a funded initiative to highlight drug delivery as a research strategy to overcome the current challenges for children diagnosed with brain tumors
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