36 research outputs found
The Secret Life of Translation Initiation in Prostate Cancer
Prostate cancer (PCa) is the second most prevalent cancer in men worldwide. Despite the advances understanding the molecular processes driving the onset and progression of this disease, as well as the continued implementation of screening programs, PCa still remains a significant cause of morbidity and mortality, in particular in low-income countries. It is only recently that defects of the translation process, i.e., the synthesis of proteins by the ribosome using a messenger (m)RNA as a template, have begun to gain attention as an important cause of cancer development in different human tissues, including prostate. In particular, the initiation step of translation has been established to play a key role in tumorigenesis. In this review, we discuss the state-of-the-art of three key aspects of protein synthesis in PCa, namely, misexpression of translation initiation factors, dysregulation of the major signaling cascades regulating translation, and the therapeutic strategies based on pharmacological compounds targeting translation as a novel alternative to those based on hormones controlling the androgen receptor pathway
Contribution of teaching in metacognitive processes and the resolution of mathematical problems
The present study evaluates the contribution of teaching from problem solving to metacognitive processes (Analysis, Planning, Local Monitoring and Global Monitoring) problem solving. The sample consisted of 41 second grade students from a public school in the department of Atlántico (Colombia). Observation was used as the main technique through video recordings of the classes, in addition the Teaching Practice Observation Format and a Semistructured Flexible Interview were used. The participants were selected by means of a nonprobabilistic sampling of intentional type. Regarding the results, the average scores in the metacognitive processes were examined, as well as their relationship at the bivariate level (Pearson's correlation) with the success in solving quantitative reasoning problems. Finally, the predictive variables of success were examined and 43.7% of the Local Monitoring variance was explained by practice at the Start of class and
39.4% of the Global Monitoring variance was explained by practice at Class Closing. . The results obtained in relation to the practice in the classroom are discussed and a series of final recommendations are suggested that contribute to the success in solving mathematical problems to make decisions directed towards the improvement of the curricular processes.El presente estudio evalúa la contribución de la enseñanza desde la resolución de problemas a los procesos Metacognitivos (Análisis, Planeación, Monitoreo Local y Monitoreo Global) de resolución de problemas. La muestra estuvo conformada por 41 estudiantes de segundo grado de un colegio público del departamento del Atlántico (Colombia). Se empleó la observación como técnica principal mediante videograbaciones de las clases, además se empleó el Formato de Observación de la Práctica Docente y se hizo una Entrevista Flexible Semiestructurada. Los participantes fueron seleccionados mediante un muestreo no probabilístico de tipo intencional. Respecto a los resultados, se examinaron las puntuaciones medias en los procesos Metacognitivos, así como su relación a nivel bivariado (correlación de Pearson) con el éxito en la resolución de problemas de razonamiento cuantitativo. Finalmente, se examinaron las variables predictoras del éxito y se comprobó el 43.7% de la varianza de Monitoreo Local fue explicada por la práctica al Inicio de clase y el 39.4% de la varianza de Monitoreo Global fue explicada por la práctica al Cierre de la Clase. Se discuten los resultados obtenidos en relación con la práctica en el aula y se sugiere una serie de recomendaciones finales que contribuyan al éxito en resolución de problemas matemáticos para tomar decisiones direccionadas hacia el mejoramiento de los procesos curriculares
A mutation in THREONINE SYNTHASE 1 uncouples proliferation and transition domains of the root apical meristem: experimental evidence and in silico proposed mechanism
A continuum from stem to transit-amplifying to a differentiated cell state is a common theme in multicellular organisms. In the plant root apical meristem (RAM), transit-amplifying cells are organized into two domains: cells from the proliferation domain (PD) are displaced to the transition domain (TD), suggesting that both domains are necessarily coupled. Here, we show that in the Arabidopsis thaliana mto2-2 mutant, in which threonine (Thr) synthesis is affected, the RAM lacks the PD. Through a combination of cell length profile analysis, mathematical modeling and molecular markers, we establish that the PD and TD can be uncoupled. Remarkably, although the RAM of mto2-2 is represented solely by the TD, the known factors of RAM maintenance and auxin signaling are expressed in the mutant. Mathematical modeling predicts that the stem cell niche depends on Thr metabolism and that, when disturbed, the normal continuum of cell states becomes aborted
A Molecular Characterization of the Allelic Expression of the BRCA1 Founder Δ9–12 Pathogenic Variant and Its Potential Clinical Relevance in Hereditary Cancer:International Journal of Molecular Sciences
Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of BRCA1 (BRCA1Δ9–12), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV BRCA1Δ9–12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT–qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9–12 alleles using nanopore long-sequencing. Using the Kruskal–Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous BRCA1 control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV BRCA1Δ9–12 and identifying which of them has developed cancer
Sex and gender differences in acute stroke care: metrics, access to treatment and outcome. A territorial analysis of the Stroke Code System of Catalonia
Introduction: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. Patients and methods: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. Results: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94–1.23; p = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97–1.22). Discussion and conclusion: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself
Emerging roles of chromatin in the maintenance of genome organization and function in plants
Detección de integrones clase I en cepas de enterobacterias productoras de β-lactamasas de espectro expandido tipo SHV y CTX-M grupo-2
The extended-spectrum-β-lactamases (ESβLs) are enzimes that
can hidrolize the amide ciclic bond of the oxyminos-β-lactamics
(cefotaxime, ceftazidime and aztreonam). These are encoded in
megaplasmids of more than 80 kDa, that generally posees others genes of
antimicrobial resistance. Recently, there have been described another
genetic structures, called integrons, through which different genes can
be stored and disseminated between strains. They posees the genetic
information requiered to express a protein (integrase), implied in the
capture and storing of antimicrobial resistance genes. In this
investigation we detected class 1 integrons in Enterobacterias that
produce ESβLs. We studied a sample of 51 Enterobacterias isolated
from seven hospitals of Caracas-Venezuela. The fenotipic and molecular
detection of ESβLs was realized, in the following, plasmids were
transfered by conjugation in a solid media and isolated from donor and
transconjugant strains. Finally class 1 integrons were detected by PCR,
employing primers for the class 1 integrase. The 68.6% of the strains
present ESβLs type SHV, 15.7% type CTX-M-group 2, and 7.8% carry
both types of ESβLs. From 36 conjugated strains, 81% transfered
plasmids carriers of genes that coded ESβLs. The analysis of the
plasmidic isolates, showed in all the transconjugant strains, a band of
25.000 pb and in a 80% a plasmidic band larger than 50.000 pb was
observed. The 27.5% (14) of donor strains and their respective
transconjugants are carriers of class 1 integrons asociated to
conjugative plasmids. The 32.4% of the strains with integrons produce
ESβLs type SHV, instead the 44.4% produce ESβLs type CTX-M