Prospección sísmica en el Glaciar Johnsons, Isla Livingston (Antártida). (campañas antárticas 1996-1997 y 1997-1998)

During two Antarctic summers (1996-97 and 1997-98), five seismic refraction (2.685 m long) and two reflection profiles (2.980 m long) were acquired on Johnsons Glacier (Livingston Island, Antarctica) in order to obtain information about the structure of the ice, characteristics of the ice-rock contact and the basement topography. Seismic refraction is an efficient method for calculating ice thickness and seismic waves velocity; whereas the seismic reflection is recommended because it leads us to a clear seismic image of bedrock topography and ice-bed contact. This study was completed using a raw data analysis (wavefront) which detected ice crevasses and delineated sectors with different glacier structures (accumulation and ablation zones). The information obtained from seismic data about the internal structure of the glacier constrains the glacial dynamics of Johnsons Glacier

Effectiveness of a pomegranate peel extract (PGE) in reducing Listeria monocytogenes in vitro and on fresh-cut pear, apple and melon

Pomegranate peel extract (PGE) is a new promising natural alternative control substance with large spectrum of activity against wide range of pathogenic microorganisms. In the present study, PGE was firstly investigated as natural antimicrobial against Listeria monocytogenes both in vitro and on fresh-cut fruits. The in vitro results showed quick and strong bactericidal and bacteriostatic activity against five different strains which were almost completely inhibited by the extract. Furthermore, it significantly decreased growth rate and maximum growth of all tested strains. In vivo trials, confirmed a strong antibacterial activity of the extract that significantly reduced the bacterial load on fresh-cut apple, melon and pear and maintained the population at low levels throughout the storage period (7 days). PGE at 12 g/l reduced L. monocytogenes by 1.24, 1.89, and 0.91 log units soon after treatment and by 3.81, 1.53, and 2.99 log units, after 7 days of storage on apple, pear and melon, respectively. This high antibacterial activity could be mainly related to the high content of polyphenols (ellagitannins) in the extract. Overall, results of this study suggest a potential industrial application of PGE to reduce the growth of the pathogenic microorganisms in fresh-cut fruit and ensure a microbial safety in case of contamination.info:eu-repo/semantics/acceptedVersio

Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer

EGFR-mutant non-small cell lung cancer are often resistant to EGFR tyrosine kinase inhibitor treatment. In this study, the authors show that resistant tumors display high Akt activation and that a combined treatment with AKT inhibitors causes synergistic tumour growth inhibition in vitro and in vivo

Usefulness of two independent DNA and rna tissue-based multiplex assays for the routine care of advanced NSCLC patients

Personalized medicine is nowadays a paradigm in lung cancer management, offering important benefits to patients. This study aimed to test the feasibility and utility of embedding two multiplexed genomic platforms as the routine workup of advanced non-squamous non-small cell lung cancer (NSCLC) patients. Two parallel multiplexed approaches were performed based on DNA sequencing and direct digital detection of RNA with nCounter® technology to evaluate gene mutations and fusions. The results were used to guide genotype-directed therapies and patient outcomes were collected. A total of 224 advanced non-squamous NSCLC patients were prospectively included in the study. Overall, 85% of samples were successfully characterized at DNA and RNA levels and oncogenic drivers were found in 68% of patients, with KRAS, EGFR, MET∆ex14, BRAF, and ALK being the most frequent (31%, 19%, 5%, 4%, and 4%, respectively). Among all patients with complete genotyping results and follow-up data (n = 156), the median overall survival (OS) was 1.90 years (confidence interval (CI) 95% 1.69-2.10) for individuals harbouring an actionable driver treated with a matched therapy, compared with 0.59 years (CI 95% 0.39-0.79) in those not eligible for any targeted therapy and 0.61 years (CI 95% 0.12-1.10) in patients with no drivers identified (p < 0.001). Integrating DNA and RNA multiplexing technologies into the routine molecular testing of advanced NSCLC patients is feasible and useful and highlights the necessity of widespread integrating comprehensive molecular diagnosis into lung cancer care

Amphiphilic Polymeric Nanoparticles Modified with a Protease-Resistant Peptide Shuttle for the Delivery of SN-38 in Diffuse Intrinsic Pontine Glioma

Diffuse intrinsic pontine glioma (DIPG) is a chemo-resistant, incurable pediatric tumor of the central nervous system (CNS). The blood–brain barrier (BBB) remains intact in the course of the disease, preventing drugs from entering the brain and resulting in therapeutic failure. The topoisomerase I inhibitor SN-38 shows strong anticancer activity in a patient-derived DIPG cell line in vitro, though a low CNS bioavailability and anti-DIPG efficacy in vivo. In this work, we produced SN-38-loaded polymeric nanoparticles of an amphiphilic chitosan (CS)-g-poly(methyl methacrylate)-poly(acrylic acid) copolymer that were surface-modified with a peptide shuttle that improves transport across the BBB. Drug-loaded nanoparticles displayed a size of ∼200 nm (intensity distribution) and a ζ-potential of +16 mV. The cytocompatibility and endocytosis assayed in DIPG cells (both attached and in suspension) indicated that the nanoparticles are compatible and mainly internalized by clathrin-mediated endocytosis and that the anticancer activity of SN-38 is preserved after nanoencapsulation. In addition, a tandem permeability/anticancer activity study utilizing a coculture model of BBB endothelial cells and DIPG cell spheroids demonstrated that the modified nanoparticles cross a BBB endothelial cell monolayer to a higher extent than the unmodified counterparts and are taken up by DIPG cells. After 72 h of exposure, both SN-38-loaded nanoparticles killed ∼84-88% of the DIPG cells in suspension, indicating that they reach a concentration above the inhibitory concentration 50 of the drug. Finally, the brain accumulation of the drug-loaded nanoparticles upon intravenous injection to Hsd:ICR mice was preliminarily characterized by light sheet fluorescence microscopy. As opposed to unmodified SN-38-loaded nanoparticles, the modified counterparts bind the brain blood vessels and accumulate in the cerebral parenchyma to a large extent. These results confirm the potential of this nanotechnology platform to deliver anticancer agents to the brain in DIPG and other brain tumors with fully conserved BBB.This work was funded by the Ministry of Health of Israel andthe 7th Framework Programme-European Commission (Proj-ect EuroNanoMed II Cure2DIPG), the Israel ScienceFoundation (Grant#269/15), and the Generalitat deCatalunya (XRB and 2017SGR0998). A.M.C. was supportedby grants from ISCIII-FEDER (CP13/00189 and CPII18/00009). IRB Barcelona is the recipient of a Severo OchoaAward of Excellence from MINECO (Government of Spain)and is supported by the CERCA Programme of the CatalanGovernment. The partial support of the Russell BerrieNanotechnology Institute (RBNI, Technion-Israel Instituteof Technology) is acknowledged. We thank Efrat Barak andNitzan Dahan (Life Sciences and Engineering InfrastructureCenter, Lorry I. Lokey Center, Technion-Israel Institute ofTechnology) for technical assistance with CLSM, LSFM, andimagingflow cytometryPeer reviewe

Anastral spindle assembly and γ-tubulin in Drosophila oocytes

<p>Abstract</p> <p>Background</p> <p>Anastral spindles assemble by a mechanism that involves microtubule nucleation and growth from chromatin. It is still uncertain whether γ-tubulin, a microtubule nucleator essential for mitotic spindle assembly and maintenance, plays a role. Not only is the requirement for γ-tubulin to form anastral <it>Drosophila </it>oocyte meiosis I spindles controversial, but its presence in oocyte meiosis I spindles has not been demonstrated and is uncertain.</p> <p>Results</p> <p>We show, for the first time, using a bright GFP fusion protein and live imaging, that the <it>Drosophila </it>maternally-expressed γTub37C is present at low levels in oocyte meiosis I spindles. Despite this, we find that formation of bipolar meiosis I spindles does not require functional γTub37C, extending previous findings by others. Fluorescence photobleaching assays show rapid recovery of γTub37C in the meiosis I spindle, similar to the cytoplasm, indicating weak binding by γTub37C to spindles, and fits of a new, potentially more accurate model for fluorescence recovery yield kinetic parameters consistent with transient, diffusional binding.</p> <p>Conclusions</p> <p>The FRAP results, together with its mutant effects late in meiosis I, indicate that γTub37C may perform a role subsequent to metaphase I, rather than nucleating microtubules for meiosis I spindle formation. Weak binding to the meiosis I spindle could stabilize pre-existing microtubules or position γ-tubulin for function during meiosis II spindle assembly, which follows rapidly upon oocyte activation and completion of the meiosis I division.</p

The Oncoprotein BCL11A Binds to Orphan Nuclear Receptor TLX and Potentiates its Transrepressive Function

Nuclear orphan receptor TLX (NR2E1) functions primarily as a transcriptional repressor and its pivotal role in brain development, glioblastoma, mental retardation and retinopathologies make it an attractive drug target. TLX is expressed in the neural stem cells (NSCs) of the subventricular zone and the hippocampus subgranular zone, regions with persistent neurogenesis in the adult brain, and functions as an essential regulator of NSCs maintenance and self-renewal. Little is known about the TLX social network of interactors and only few TLX coregulators are described. To identify and characterize novel TLX-binders and possible coregulators, we performed yeast-two-hybrid (Y2H) screens of a human adult brain cDNA library using different TLX constructs as baits. Our screens identified multiple clones of Atrophin-1 (ATN1), a previously described TLX interactor. In addition, we identified an interaction with the oncoprotein and zinc finger transcription factor BCL11A (CTIP1/Evi9), a key player in the hematopoietic system and in major blood-related malignancies. This interaction was validated by expression and coimmunoprecipitation in human cells. BCL11A potentiated the transrepressive function of TLX in an in vitro reporter gene assay. Our work suggests that BCL11A is a novel TLX coregulator that might be involved in TLX-dependent gene regulation in the brain

Selenomethionine Incorporation into Amyloid Sequences Regulates Fibrillogenesis and Toxicity

The capacity of a polypeptide chain to engage in an amyloid formation process and cause a conformational disease is contained in its sequence. Some of the sequences undergoing fibrillation contain critical methionine (Met) residues which in vivo can be synthetically substituted by selenomethionine (SeM) and alter their properties