315 research outputs found
Image Management in a Touristic Destination: A Qualitative Approach Analysis of the Border City of Ciudad Juarez, Mexico
This paper summarizes an academic experience. It has been made by the contributions of a group of experts from a Mexican university participating in a discussion panel called "Image of a Touristic Destination". This was done within the framework of the activities carried out during the 8va. Catedra Patrimonial "Sergio Molina" on October 19-21, 2016. The purpose of this paper is to analyze the process of image management of a border touristic destination through the experience of Ciudad Juárez, in order to obtain an improvement in it. The concept of image is analyzed from its components of responsibility and participation in management between Government (message), Society (context), and Universities (management). The methodological approach selected was exploratory. The grounded theory method was selected and thematic analysis with the support of the Atlas-ti software was made. Suggestions are offered for actions which seek to highlight the positive aspects of the city as a touristic destination. The importance of generating responsibility and participation within a social network was highlighted. It was recommended to take advantage of the economic and intellectual resources in education of the Juarez society so that they can know their culture and history
Selective Fractionation And Isolation Of Allelopathic Compounds From Helianthus Annuus L. Leaves By Means Of High-Pressure Techniques
The allelopathic potential of Helianthus annuus L. leaves was study based on bio-directed chemical fractionation approach. Aerial parts of H. annuus were extracted by means of SFE using supercritical carbon dioxide (scCO2) and ESE using CO2+50% EtOH/H2O (varying ethanol in water from 0 to 100%). Extractions were carried out at 400 bar, 55 °C, 20 g/min and for 4 h. Then, extracts were fractionated in three separators at the following conditions: S1: 200 bar/45 °C; S2: 90 bar/40 °C; and S3: 1 atm/30 °C. ESE obtained higher overall yields than scCO2 and the use of water as cosolvent (CO2+50% H2O) resulted in a S3 fraction free from chlorophylls and rich in bioactive compounds. 14 compounds, including fatty acids, terpenes, flavonoids and heliannuols, were isolated from this fraction. After performing the bioassay on pure compounds, heliannuol D, tambulin, pinoresinol and sesquiterpene 10-oxo-isodauc-3-en-15-al showed the most effective inhibitor profiles
Novel purine chemotypes with activity against Plasmodium 2 falciparum and Trypanosoma cruzi
Malaria and Chagas disease, caused by Plasmodium spp. and Trypanosoma cruzi parasites,
remain important global health problems. Available treatments for those diseases present several
limitations, such as lack of efficacy, toxic side effects, and drug resistance. Thus, new drugs are urgently needed. The discovery of new drugs may be benefited by considering the significant biological
differences between hosts and parasites. One of the most striking differences is found in the purine
metabolism, because most of the parasites are incapable of de novo purine biosynthesis. Herein,
we have analyzed the in vitro anti-P. falciparum and anti-T. cruzi activity of a collection of 81 purine
derivatives and pyrimidine analogs. We firstly used a primary screening at three fixed concentrations
(100, 10, and 1 µM) and progressed those compounds that kept the growth of the parasites < 30%
at 100 µM to dose–response assays. Then, we performed two different cytotoxicity assays on Vero
cells and human HepG2 cells. Finally, compounds specifically active against T. cruzi were tested
against intracellular amastigote forms. Purines 33 (IC50 = 19.19 µM) and 76 (IC50 = 18.27 µM) were
the most potent against P. falciparum. On the other hand, 6D (IC50 = 3.78 µM) and 34 (IC50 = 4.24 µM)
were identified as hit purines against T. cruzi amastigotes. Moreover, an in silico docking study
revealed that P. falciparum and T. cruzi hypoxanthine guanine phosphoribosyltransferase enzymes
could be the potential targets of those compounds. Our study identified two novel, purine-based
chemotypes that could be further optimized to generate potent and diversified anti-parasitic drugs
against both parasites.SAF2016-76080-R (Spanish Ministry of Economy
(AEI/FEDER, UE))PID2019-110810RB-I00 (Spanish Ministry of Science and Innovation)Generalitat of Catalonia Universities and Research
Department, Spain (AGAUR; 2017SGR00924)Carlos III Health Institute
(ISCIII)RICET Network for Cooperative Research in Tropical Diseases (ISCIII; RD12/0018/0010)Generalitat of Catalonia Department of Health (PERIS 2016–2010
SLT008/18/00132)Spanish Ministry of Education, Culture, and
Sports (FPU grant ref. 14/00818)Spanish Ministry of Science,
Innovation, and Universities through the “Centro de Excelencia Severo Ochoa 2019–2023” Program
(CEX2018-000806-S)CERCA Progra
Further Characterization of the Electrogenicity and pH Sensitivity of the Human Organic Anion-Transporting Polypeptides OATP1B1 and OATP1B3
Organic anion-transporting polypeptides (OATPs) are involved in the liver uptake of many endogenous and xenobiotic compounds, such as bile acids and drugs, respectively. Using Xenopus laevis oocytes and Chinese hamster ovary (CHO) cells expressing rat Oatp1a1, human OATP1B1, or OATP1B3, the sensitivity of these transporters to extracellular/intracellular pH (pHo/pHi) and changes in plasma membrane potential (ΔΨ) was investigated. In X. laevis oocytes, nonspecific plasma membrane permeability increased only at pHo below 4.5. Above this value, both using oocytes and CHO cells, extracellular acidification affected differently the specific transport of taurocholic acid (TCA) and estradiol 17β-d-glucuronide (E217βG) by Oatp1a1 (stimulation), OATP1B1 (inhibition), and OATP1B3 (stimulation). Changes in substrate uptake in the presence of valinomycin (K+-ionophore), carbonyl cyanide 3-chlorophenylhydrazone and nigericin (protonophores), and amiloride (Na+/H+-inhibitor) and cation replacement in the medium were studied with fluorescent probes for measuring substrate uptake (cholylglycyl amidofluorescein) and changes in pHi (SNARF-4F) and ΔΨ [DilC1(5)]. The results suggest that activity of these three carriers is sodium/potassium-independent and affected differently by changes in pHo and ΔΨ: Oatp1a1 was confirmed to be an electroneutral anion exchanger, whereas the function of both OATP1B1 and OATP1B3 was markedly affected by the magnitude of ΔΨ. Moreover, electrophysiological measurements revealed the existence of a net anion influx associated to OATP1B1/OATP1B3-mediated transport of TCA, E217βG, and estrone-3-sulfate. Furthermore, a leakage of Na+ through OATP1B1 and OATP1B3, which is not coupled to substrate transport, was found. In conclusion, these results suggest that OATP1B1 and OATP1B3 are electrogenic transporters whose activity may be strongly affected under circumstances of displacement of local pH
THz streak camera performance for single-shot characterization of XUV pulses with complex temporal structures
The THz-field-driven streak camera has proven to be a powerful diagnostic-technique that enables the shot-to-shot characterization of the duration and the arrival time jitter of free electron laser (FEL) pulses. Here we investigate the performance of three computational approaches capable to determine the duration of FEL pulses with complex temporal structures from single-shot measurements of up to three simultaneously recorded spectra. We use numerically simulated FEL pulses in order to validate the accuracy of the pulse length retrieval in average as well as in a single-shot mode. We discuss requirements for the THz field strength in order to achieve reliable results and compare our numerical study with the analysis of experimental data that were obtained at the FEL in Hamburg - FLASH. © 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen
Clinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions
Cholangiocarcinoma (CCA) is a malignant tumour arising from the biliary system. In Europe, this tumour frequently presents as a sporadic cancer in patients without defined risk factors and is usually diagnosed at advanced stages with a consequent poor prognosis. Therefore, the identification of biomarkers represents an utmost need for patients with CCA. Numerous studies proposed a wide spectrum of biomarkers at tissue and molecular levels. With the present paper, a multidisciplinary group of experts within the European Network for the Study of Cholangiocarcinoma discusses the clinical role of tissue biomarkers and provides a selection based on their current relevance and potential applications in the framework of CCA. Recent advances are proposed by dividing biomarkers based on their potential role in diagnosis, prognosis and therapy response. Limitations of current biomarkers are also identified, together with specific promising areas (ie, artificial intelligence, patient-derived organoids, targeted therapy) where research should be focused to develop future biomarkers
Multi-Messenger Astronomy with Extremely Large Telescopes
The field of time-domain astrophysics has entered the era of Multi-messenger
Astronomy (MMA). One key science goal for the next decade (and beyond) will be
to characterize gravitational wave (GW) and neutrino sources using the next
generation of Extremely Large Telescopes (ELTs). These studies will have a
broad impact across astrophysics, informing our knowledge of the production and
enrichment history of the heaviest chemical elements, constrain the dense
matter equation of state, provide independent constraints on cosmology,
increase our understanding of particle acceleration in shocks and jets, and
study the lives of black holes in the universe. Future GW detectors will
greatly improve their sensitivity during the coming decade, as will
near-infrared telescopes capable of independently finding kilonovae from
neutron star mergers. However, the electromagnetic counterparts to
high-frequency (LIGO/Virgo band) GW sources will be distant and faint and thus
demand ELT capabilities for characterization. ELTs will be important and
necessary contributors to an advanced and complete multi-messenger network.Comment: White paper submitted to the Astro2020 Decadal Surve
Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis
Cholangiocarcinoma (CCA) comprises a group of heterogeneous biliary cancers with
dismal prognosis. The etiologies of most CCAs are unknown, but primary sclerosing cholangitis
(PSC) is a risk factor. Non-invasive diagnosis of CCA is challenging and accurate biomarkers are
lacking. We aimed to characterize the transcriptomic profile of serum and urine extracellular
vesicles (EVs) from patients with CCA, PSC, ulcerative colitis (UC), and healthy individuals. Serum
and urine EVs were isolated by serial ultracentrifugations and characterized by nanoparticle
tracking analysis, transmission electron microscopy, and immunoblotting. EVs transcriptome was
determined by Illumina gene expression array [messenger RNAs (mRNA) and non-coding RNAs
(ncRNAs)]. Differential RNA profiles were found in serum and urine EVs from patients with CCA
compared to control groups (disease and healthy), showing high diagnostic capacity. The
comparison of the mRNA profiles of serum or urine EVs from patients with CCA with the
transcriptome of tumor tissues from two cohorts of patients, CCA cells in vitro, and CCA cellsderived EVs, identified 105 and 39 commonly-altered transcripts, respectively. Gene ontology
analysis indicated that most commonly-altered mRNAs participate in carcinogenic steps. Overall,
patients with CCA present specific RNA profiles in EVs mirroring the tumor, and constituting novel
promising liquid biopsy biomarkers
Frequency of Fabry disease in male and female haemodialysis patients in Spain
<p>Abstract</p> <p>Background</p> <p>Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by a reduced activity of the lysosomal enzyme α-galactosidase A. The disorder ultimately leads to organ damage (including renal failure) in males and females. However, heterozygous females usually present a milder phenotype with a later onset and a slower progression.</p> <p>Methods</p> <p>A combined enzymatic and genetic strategy was used, measuring the activity of α-galactosidase A and genotyping the α-galactosidase A gene (<it>GLA</it>) in dried blood samples (DBS) of 911 patients undergoing haemodialysis in centers across Spain.</p> <p>Results</p> <p><it>GLA </it>alterations were found in seven unrelated patients (4 males and 3 females). Two novel mutations (p.Gly346AlafsX347 and p.Val199GlyfsX203) were identified as well as a previously described mutation, R118C. The R118C mutation was present in 60% of unrelated patients with <it>GLA </it>causal mutations. The D313Y alteration, considered by some authors as a pseudo-deficiency allele, was also found in two out of seven patients.</p> <p>Conclusions</p> <p>Excluding the controversial D313Y alteration, FD presents a frequency of one in 182 individuals (0.55%) within this population of males and females undergoing haemodialysis. Moreover, our findings suggest that a number of patients with unexplained and atypical symptoms of renal disease may have FD. Screening programmes for FD in populations of individuals presenting severe kidney dysfunction, cardiac alterations or cerebrovascular disease may lead to the diagnosis of FD in those patients, the study of their families and eventually the implementation of a specific therapy.</p
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