17 research outputs found
Evaluation of the copper and zinc contents of soils in the vineyards of La Rioja (Spain)
The aim of this study was to determine the concentrations of Cu and Zn in soils in the vineyards of La Rioja and to calculate reference values for the two elements. Samples were taken from the surface horizon (0â20 cm) and the subsurface horizon (40â60 cm) in 106 locations. Some physico-chemical properties were analyzed along with the total and bioavailable contents of these elements. Various statistical parameters were calculated, and distribution maps were then created using the ordinary-Kriging method. The Cu content was in the range of 2.46â121.52 mg kgâ1, and the Zn content was 9.05â125.67 mg kgâ1. These values fell within the normal ranges in comparison with other areas of Spain and the rest of Europe. The concentrations in the surface and in the subsurface were compared; in the case of Cu, the concentration was higher at the surface, whereas significant differences in the vertical distribution of Zn were not observed. Both metals had a heterogeneous distribution across the entire area of study. In the case of Zn, the similarity of the maps between surface and depth was verified, while the case of Cu was different. The main source of these metals was the parent material from which the soil had been formed, but in the case of Cu, maps showed increased Cu at the surface, which was especially marked at certain points and seemed to indicate the presence of an exogenous contribution at these locations. That means that the copper concentrations in the topsoil resulted from the yearlong grapevine protection with copper-based agents. Reference values were calculated to be 85.28 and 48.88 mg kgâ1 of Cu and 83.69 and 72.05 mg kgâ1 for Zn at the surface and at depth, respectivelyThis Research was funded by Regional Government of La Rioja (Gobierno de La Rioja, Spain
SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade
Cancer therapyTerĂ pia del cĂ ncerTerapia del cĂĄncerDespite the genetic inactivation of SMARCA4, a core component of the SWI/SNF-complex commonly found in cancer, there are no therapies that effectively target SMARCA4-deficient tumours. Here, we show that, unlike the cells with activated MYC oncogene, cells with SMARCA4 inactivation are refractory to the histone deacetylase inhibitor, SAHA, leading to the aberrant accumulation of H3K27me3. SMARCA4-mutant cells also show an impaired transactivation and significantly reduced levels of the histone demethylases KDM6A/UTX and KDM6B/JMJD3, and a strong dependency on these histone demethylases, so that its inhibition compromises cell viability. Administering the KDM6 inhibitor GSK-J4 to mice orthotopically implanted with SMARCA4-mutant lung cancer cells or primary small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), had strong anti-tumour effects. In this work we highlight the vulnerability of KDM6 inhibitors as a characteristic that could be exploited for treating SMARCA4-mutant cancer patients
BCL7A is silenced by hypermethylation to promote acute myeloid leukemia
The online version contains supplementary material available at https:// doi.
org/ 10. 1186/ s40364â 023â 00472âx.
Additional file 1: Supplementary Figure 1. Diagram displaying CpGâ
methylation status around the BCL7A TSS. Genomic DNA from the NB4 cell
line was subjected to bisulfite conversion and used for subsequent TAâ
cloning. Supplementary Figure 2. Schematic representation of the differâ
ent lentiviral plasmids used in the experimental procedures. The specific
region of the long isoform of BCL7A is colored in blue. Supplementary
Figure 3. Western blot including the Decitabine (DAC) treatment over the
NB4 cell line shown in Fig. 2c. Supplementary Figure 4. Proteinâprotein
interactions between BCL7A and SMARCA4 as determined by Mashtalir
et al (2020). Supplementary Figure 5. DepMap AML cell lines collection
data showing BCL7A Methylation Fraction (1kb upstream TSS) vs BCL7Aexâ
pression level. NB4 and M07e are marked. Supplementary Figure 6.
Competition cell growth effect of BCL7A expression restoration on in vitro
proliferation. Supplementary Table 1.
Additional file 2: Supplementary Table 2. Differential expression
analysis resultsP.P.M.âs laboratory is funded by ConsejerĂa de Universidad, InvestigaciĂłn e InnovaciĂłn de la Junta de AndalucĂa and FEDER (P20â00688), Aula de InvestigaciĂłn sobre la Leucemia infantil: Heroes contra la Leucemia, the Ministry of Science and Innovation of Spain (grant PID2021â126111OBâI00), Junta de AndalucĂa (grants PIGEâ0440â2019, PIâ0135â2020), the University of Granada (grants BâCTSâ126âUGR18, BâCTSâ480âUGR20, and EâCTSâ304âUGR20), and the Spanish Association for Cancer Research (LABORATORYâAECCâ2018). J.R.PâM, A.A, and M.S.BâC were supported by fellowships FPU18/03709, FPU17/00067, and FPU19/00576 respectively funded by the Spanish Ministry of Science, Innovation and UniversitiesBackground Recent massive sequencing studies have revealed that SWI/SNF complexes are among the most freâ
quently altered functional entities in solid tumors. However, the role of SWI/SNF in acute myeloid leukemia is poorly
understood. To date, SWI/SNF complexes are thought to be oncogenic in AML or, at least, necessary to support leukeâ
mogenesis. However, mutation patterns in SWI/SNF genes in AML are consistent with a tumor suppressor role. Here,
we study the SWI/SNF subunit BCL7A, which has been found to be recurrently mutated in lymphomas, but whose
role in acute myeloid malignancies is currently unknown.
Methods Data mining and bioinformatic approaches were used to study the mutational status of BCL7A and the
correlation between BCL7A expression and promoter hypermethylation. Methylationâspecific PCR, bisulfite sequencâ
ing, and 5âazaâ2ââdeoxycytidine treatment assays were used to determine if BCL7A expression was silenced due to
promoter hypermethylation. Cell competition assays after BCL7A expression restoration were used to assess the role
of BCL7A in AML cell line models. Differential expression analysis was performed to determine pathways and genes
altered after BCL7A expression restoration. To establish the role of BCL7A in tumor development in vivo, tumor growth
was compared between BCL7Aâexpressing and nonâexpressing mouse xenografts using in vivo fluorescence imaging.
Results BCL7A expression was inversely correlated with promoter methylation in three external cohorts: TCGAâLAML
(N = 160), TARGETâAML (N = 188), and Glass et al. (2017) (N = 111). The AMLâderived cell line NB4 silenced the BCL7A
expression via promoter hypermethylation. Ectopic BCL7A expression in AML cells decreased their competitive ability
compared to control cells. Additionally, restoration of BCL7A expression reduced tumor growth in an NB4 mouse
xenograft model. Also, differential expression analysis found that BCL7A restoration altered cell cycle pathways and
modified significantly the expression of genes like HMGCS1, H1-0, and IRF7 which can help to explain its tumor supâ
pressor role in AML.
Conclusions BCL7A expression is silenced in AML by promoter methylation. In addition, restoration of BCL7A expresâ
sion exerts tumor suppressor activity in AML cell lines and xenograft models.ConsejerĂa de Universidad, InvestigaciĂłn e InnovaciĂłn de la Junta de AndalucĂa and FEDER (P20â00688)Ministry of Science and Innovation of Spain (grant PID2021â126111OBâI00)Junta de AndalucĂa (grants PIGEâ0440â2019, PIâ0135â2020)University of Granada (BâCTSâ126âUGR18, BâCTSâ480âUGR20, EâCTSâ304âUGR20)Spanish Association for Cancer Research (LABORATORYâAECCâ2018)Spanish Ministry of Science, Innovation and Universities FPU18/03709, FPU17/00067, FPU19/0057
Estado del arte de la medición de la productividad y la eficiencia técnica en América Latina: Caso Nicaragua
En este artĂculo se plasman los resultados de una revisiĂłn bibliogrĂĄfica de textos y artĂculos cientĂficos que abordan la teorĂa de la âProductividadâ y de la âEficiencia tĂ©cnicaâ como dos magnitudes econĂłmicas claves para determinar el crecimiento econĂłmico de una unidad productiva, un sector econĂłmico o de una naciĂłn. En el estudio se encontrĂł que los paĂses donde se registrĂł una mayor contribuciĂłn del progreso tĂ©cnico a la variaciĂłn de la productividad en el perĂodo de 50 años (de 1960-2010) analizado fueron la Argentina, el Brasil, Colombia y el Ecuador, con Ăndices de alrededor del 0,3%. AdemĂĄs, se evidencia que los 19 paĂses analizados en este trabajo registraron una eficiencia tĂ©cnica decreciente, que supone que el aporte de dicha eficiencia a la PTF fue negativo en todos los paĂses.  En el caso de Nicaragua se notĂł que la PTF algunos autores la estimaron entre un 0.08 y 0.016 de ritmo de crecimiento interanual.Palabras Claves: Productividad, Eficiencia TĂ©cnica, Cambio tecnolĂłgico, Fronteras de producciĂłn.Jel Classification:  F:64; P:28; Q:54
The use of intra-SMAS absorbable barbed sutures to reinforce a high-vector pull during rhytidectomy
The Use of Intra-SMAS Absorbable Barbed Sutures to Reinforce a High-Vector Pull during Rhytidectomy
Multi-omic alterations of the SWI/SNF complex define a clinical subgroup in lung adenocarcinoma.
SWI/SNF complexes are major targets of mutations in cancer. Here, we combined multiple "-omics" methods to assess SWI/SNF composition and aberrations in LUAD. Mutations in lung SWI/SNF subunits were highly recurrent in our LUAD cohort (41.4%), and over 70% of the mutations were predicted to have functional impact. Furthermore, SWI/SNF expression in LUAD suffered an overall repression that could not be explained exclusively by genetic alterations. Finally, SWI/SNF mutations were associated with poorer overall survival in TCGA-LUAD. We propose SWI/SNF-mutant LUAD as a separate clinical subgroup with practical implications