FoxE1 is a thyroid-specific forkhead transcription factor essential for thyroid gland development, as well as for the maintenance of the thyroid differentiated state in adults. FoxE1 recognizes and ...binds to a short DNA sequence present in thyroglobulin (Tg) and thyroperoxidase (Tpo) promoters, but FoxE1 binding to regulatory regions other than Tg and Tpo promoters remains almost unexplored. Improving knowledge of the regulatory functions of FoxE1 is necessary to clarify its role in endocrine syndromes and cancer susceptibility.
In order to further investigate downstream FoxE1 targets, we performed a genome-wide expression screening after knocking-down FoxE1 and obtained new insights into FoxE1 transcriptional networks in thyroid follicular cells. After validation, we confirmed Adamts9, Cdh1, Duox2 and S100a4 as upregulated genes and Casp4, Creld2, Dusp5, Etv5, Hsp5a, Nr4a2 and Tm4sf1 as downregulated genes when FoxE1 was silenced. In promoter regions of putative FoxE1-regulated genes and also in the promoters of the classical thyroid genes Nis, Pax8 and Titf1, we performed an in silico search of the FoxE1 binding motif that was in close proximity to the NF1/CTF binding sequence, as previously described for other forkhead factors. Using chromatin immunoprecipitation we detected specific in vivo FoxE1 binding to novel regulatory regions in two relevant thyroid genes, Nis and Duox2. Moreover, we demonstrated simultaneous binding of FoxE1 and NF1/CTF to the Nis upstream enhancer region, as well as a clear functional activation of the Nis promoter by both transcription factors.
In search for potential downstream mediators of FoxE1 function in thyroid cells, we identified two novel direct FoxE1 target genes. To our knowledge, this is the first evidence regarding the implication of Nis and Duox2 in executing the transcriptional program triggered by FoxE1. Furthermore, this study points out the important role of FoxE1 in the regulation of a large number of genes in thyroid cells.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Climate change (CC) and sea level rise (SLR) are phenomena that could have severe impacts on the distribution of coastal dune vegetation. To explore this we modeled the climatic niches of six coastal ...dunes plant species that grow along the shoreline of the Gulf of Mexico and the Yucatan Peninsula, and projected climatic niches to future potential distributions based on two CC scenarios and SLR projections. Our analyses suggest that distribution of coastal plants will be severely limited, and more so in the case of local endemics (Chamaecrista chamaecristoides, Palafoxia lindenii, Cakile edentula). The possibilities of inland migration to the potential ‘new shoreline’ will be limited by human infrastructure and ecosystem alteration that will lead to a ‘coastal squeeze’ of the coastal habitats. Finally, we identified areas as future potential refuges for the six species in central Gulf of Mexico, and northern Yucatán Peninsula especially under CC and SLR scenarios.
Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of ...studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n = 90) or diagnosed with NAFLD (steatosis, n = 246; NASH, n = 131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC–MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual’s level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values = 0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention.
In this study, we aimed to develop and validate a quick, easy, and robust extraction method for the simultaneous determination of 30 organic contaminants of emerging concern (CECs) including some ...transformation products in soil samples. Three different extraction methods based on an ultrasonic cylindrical probe (UAE), a pressurized liquid extraction (PLE), and a QuEChERS method were compared. Ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry (LC-MS/MS) was used for identification and quantification of the target analytes. A modified QuEChERS method showed the best results in terms of extractability and accuracy. The extraction procedure developed provided adequate extraction performances (70% of the target analytes were recovered within a 70–99% range), with good repeatability and reproducibility (variations below 20%) and great sensitivity (LOQ < 0.1 ng/g in most cases). No matrix effects were observed for 70% of the compounds. Finally, the analytical methodology was applied in a pilot study where agricultural soil was irrigated with reclaimed water spiked with the contaminants under study. Of the 25 CECs added in irrigation water, a total of 13 pesticides and 5 pharmaceutical products were detected at concentration ranges from 0.1 to 1.2 ng/g (d.w) and from 0.1 to 2.0 ng/g (d.w), respectively.
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•Three different extraction methods were developed and compared.•All they affordable for routinely control laboratories•Sensitive quantification of 30 contaminants of emerging concern in agricultural soil•A modified QuEChERS method showed the best results.•A pilot study was carried out in real agronomic conditions in a greenhouse.
Background: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic ...women complete androgen insensitivity syndrome (CAIS) to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS).
Objective: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients.
Setting: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis.
Methods: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients.
Results: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4–8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel.
Conclusions: AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002–2009 were novel.
AR gene mutations detected during the period 2002–2009 and present in 59 index patients show that 60% of them are novel.
Dalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an ...interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related infection) treated with at least one dose of dalbavancin between 2016 and 2017 in 30 institutions in Spain. In order to evaluate the response, patients with or without an orthopedic implant were separated. A total of 64 patients were included.
and
were the most frequent microorganisms. The reasons for switching to dalbavancin were simplification (53.1%), adverse events (25%), or failure (21.9%). There were 7 adverse events, and no patient had to discontinue dalbavancin. In 45 cases, infection was related to an orthopedic implant. The implant material was retained in 23 cases, including that in 15 (65.2%) patients that were classified as cured and 8 (34.8%) that presented improvement. In 21 cases, the implants were removed, including those in 16 (76.2%) cases that were considered successes, 4 (19%) cases were considered improved, and 1 (4.8%) case that was considered a failure. Among the 19 cases without implants, 14 (73.7%) were considered cured, 3 (15.8%) were considered improved, and 2 (10.5%) were considered failures. The results show that dalbavancin is a well-tolerated antibiotic, even when >2 doses are administered, and is associated with a high cure rate. These are preliminary data with a short follow-up; therefore, it is necessary to gain more experience and, in the future, to establish the most appropriate dose and frequency.
Small-scale portable rainfall simulators are an essential research tool for investigating the process dynamics of soil erosion and surface hydrology. There is no standardisation of rainfall ...simulation and such rainfall simulators differ in design, rainfall intensities, rain spectra and research questions, which impede drawing a meaningful comparison between results. Nevertheless, these data become progressively important for soil erosion assessment and therefore, the basis for decision-makers in application-oriented erosion protection.
The artificially generated rainfall of the simulators used at the Universities Basel, La Rioja, Malaga, Trier, Tübingen, Valencia, Wageningen, Zaragoza, and at different CSIC (Spanish Scientific Research Council) institutes (Almeria, Cordoba, Granada, Murcia and Zaragoza) was measured with the same methods (Laser Precipitation Monitor for drop spectra and rain collectors for spatial distribution). Data are very beneficial for improvements of simulators and comparison of simulators and results. Furthermore, they can be used for comparative studies, e.g. with measured natural rainfall spectra. A broad range of rainfall data was measured (e.g. intensity: 37–360mmh−1; Christiansen Coefficient for spatial rainfall distribution: 61–98%; median volumetric drop diameter: 0.375–6.5mm; mean kinetic energy expenditure: 25–1322Jm−2h−1; mean kinetic energy per unit area and unit depth of rainfall: 0.77–50Jm−2mm−1). Similarities among the simulators could be found e.g. concerning drop size distributions (maximum drop numbers are reached within the smallest drop classes <1mm) and low fall velocities of bigger drops due to a general physical restriction. The comparison represents a good data-base for improvements and provides a consistent picture of the different parameters of the simulators that were tested.
•Small portable rainfall simulators in soil erosion and soil hydrology studies•Detailed investigation of simulated rainfall characteristics•Comparison of artificial rainfall generated by 13 rainfall simulators based in Europe•Identical methods in all simulations to ensure comparability•Methods: Laser Precipitation Monitor and rain collectors
Using reclaimed water for agricultural irrigation is increasing worldwide to compensate for water scarcity. The aim of this work was to evaluate the uptake of some of the most commonly detected ...organic contaminants of emerging concern (CECs) and pesticides in regenerated water in a field study. Furthermore, it was studied their distribution and accumulation in the different parts of a crop (soil, plant and fruit). Three crops (cucumber, pepper and melon) were grown under controlled agronomic conditions in a greenhouse. In order to make an accurate evaluation of the process, “regenerated blank water” was spiked with 70 chemicals (including antibiotics, anti-inflammatories, analgesics, anaesthetics, anxiolytics, anticonvulsants, pesticides) at environmental concentrations (∼1 μg/L) and used for continuous crop irrigation. After crop season, the average total concentration of contaminants detected in the soil samples ranged from 132 to 232 μg/kg d.w depending of the crops type. Between 7 and 10 different contaminants were found in the harvested fruits, up to levels of 27.8 μg/kg f.w. cucumber, 12.4 μg/kg f.w. melon and 7.8 μg/kg f.w pepper. In general, cucumber fruit showed higher accumulation levels of contaminants than pepper and melon for most target analytes. The accumulation rates followed the order: root (0.2 %) < stem/leaf (1–4 %) < fruit (1–6 %) < soil (17–30 %). The experimental data obtained in this study were also used to assess the risk associated with the reuse of reclaimed water for crop irrigation as well to identify those contaminants that, due to their physicochemical properties, show higher accumulation rates and environmental impact.
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•Three different crops under realistic field/environmental conditions were evaluated.•Cucumber showed the highest content of contaminants followed by melon and pepper.•Clonazepam exhibited the greatest accumulation rates in all fruits.•The results pointed to the importance of soil control when reclaimed water is used.•No human risk associated with the consumption of irrigated vegetables was observed.
The six most important cost-effective policies on tobacco control can be measured by the Tobacco Control Scale (TCS). The objective of our study was to describe the correlation between the TCS and ...smoking prevalence, self-reported exposure to secondhand smoke (SHS) and attitudes towards smoking restrictions in the 27 countries of the European Union (EU27).
Ecologic study in the EU27. We used data from the TCS in 2007 and from the Eurobarometer on Tobacco Survey in 2008. We analysed the relations between the TCS and prevalence of smoking, self-reported exposure to SHS (home and work), and attitudes towards smoking bans by means of scatter plots and Spearman rank-correlation coefficients (r(sp)). Among the EU27, smoking prevalence varied from 22.6% in Slovenia to 42.1% in Greece. Austria was the country with the lowest TCS score (35) and the UK had the highest one (93). The correlation between smoking prevalence and TCS score was negative (r(sp) = -0.42, p = 0.03) and the correlation between TCS score and support to smoking bans in all workplaces was positive (r(sp) = 0.47, p = 0.01 in restaurants; r(sp) = 0.5, p = 0.008 in bars, pubs, and clubs; and r(sp) = 0.31, p = 0.12 in other indoor workplaces). The correlation between TCS score and self-reported exposure to SHS was negative, but statistically non-significant.
Countries with a higher score in the TCS have higher support towards smoking bans in all workplaces (including restaurants, bars, pubs and clubs, and other indoor workplaces). TCS scores were strongly, but not statistically, associated with a lower prevalence of smokers and a lower self-reported exposure to SHS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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