Genome‑wide analysis of CCHC‑type zinc finger (ZCCHC) proteins in yeast, Arabidopsis, and humans

The diverse eukaryotic proteins that contain zinc fingers participate in many aspects of nucleic acid metabolism, from DNA transcription to RNA degradation, post-transcriptional gene silencing, and small RNA biogenesis. These proteins can be classified into at least 30 types based on structure. In this review, we focus on the CCHC-type zinc fingers (ZCCHC), which contain an 18-residue domain with the CX2CX4HX4C sequence, where C is cysteine, H is histidine, and X is any amino acid. This motif, also named the “zinc knuckle”, is characteristic of the retroviral Group Antigen protein and occurs alone or with other motifs. Many proteins containing zinc knuckles have been identified in eukaryotes, but only a few have been studied. Here, we review the available information on ZCCHC-containing factors from three evolutionarily distant eukaryotes—Saccharomyces cerevisiae, Arabidopsis thaliana, and Homo sapiens—representing fungi, plants, and metazoans, respectively. We performed systematic searches for proteins containing the CX2CX4HX4C sequence in organism-specific and generalist databases. Next, we analyzed the structural and functional information for all such proteins stored in UniProtKB. Excluding retrotransposon-encoded proteins and proteins harboring uncertain ZCCHC motifs, we found seven ZCCHC-containing proteins in yeast, 69 in Arabidopsis, and 34 in humans. ZCCHC-containing proteins mainly localize to the nucleus, but some are nuclear and cytoplasmic, or exclusively cytoplasmic, and one localizes to the chloroplast. Most of these factors participate in RNA metabolism, including transcriptional elongation, polyadenylation, translation, pre-messenger RNA splicing, RNA export, RNA degradation, microRNA and ribosomal RNA biogenesis, and post-transcriptional gene silencing. Several human ZCCHC-containing factors are derived from neofunctionalized retrotransposons and act as proto-oncogenes in diverse neoplastic processes. The conservation of ZCCHCs in orthologs of these three phylogenetically distant eukaryotes suggests that these domains have biologically relevant functions that are not well known at present

Missplicing suppressor alleles of Arabidopsis PRE-MRNA Processing factor 8 increase splicing fidelity by reducing the use of novel splice sites

El empalme eficiente requiere un equilibrio entre la selección del sitio de empalme (SS) de alta fidelidad y la velocidad. En Saccharomyces cerevisiae , el factor de procesamiento pre-ARNm 8 (Prp8) ayuda a equilibrar la selección precisa de SS y la escisión de intrones y la unión de exones rápida y eficiente. argonaute1-52 ( ago1-52 ) e incurvata13 ( icu13 ) son alelos hipomórficos de los genes de Arabidopsis thaliana ARGONAUTE1 ( AGO1 ) y AUXIN RESISTANT6 ( AXR6 ) que albergan mutaciones puntuales que crean nuevos 3′SS y 5′SS, respectivamente. El espliceosoma reconoce estos nuevos SS, así como los SS genuinos intactos, produciendo una mezcla de ARNm maduros aberrantes y de tipo salvaje. Aquí, caracterizamos cinco nuevos alelos mutantes de PRP8 (uno de los dos coortólogos de levadura Prp8 de Arabidopsis ), nombrando la morfología de estos alelos de ago1-52 suprimido5 ( mas5 ). En el fondo mas5-1 , el espliceosoma reconoce preferentemente el 3′SS genuino intacto de ago1-52 y el 5′SS de icu13 . Dado que las mutaciones puntuales que dañan los SS genuinos hacen que el espliceosoma sea propenso a reconocer SS crípticos, también analizamos los alelos de cuatro genes que portan SS genuinos dañados y descubrimos que mas5-1 no suprimió su error de empalme. Las mutaciones mas5-1 y mas5-3 representan una nueva clase de supresores de empalme incorrecto que aumentan la fidelidad del empalme al dificultar el uso de nuevos SS, pero no alteran el empalme general del pre-ARNm

Valoración del centro histórico del Rímac para el fortalecimiento de la identidad cultural en los estudiantes del tercer año de educación secundaria de la Institución Educativa María Parado de Bellido, año 2019

El presente trabajo tuvo como objetivo general determinar en qué medida el desarrollo de un Programa de Valoración del Centro Histórico del Rímac influye en el fortalecimiento de la identidad cultural en las estudiantes del tercer año de educación secundaria de la Institución Educativa María Parado de Bellido. Asimismo, la presente investigación ha sido diseñada desde un enfoque cuantitativo para lo cual se aplicó un Programa de Valoración del Centro Histórico del distrito del Rímac, dirigido a 32 estudiantes de la sección “A” (grupo experimental) del 3er año de secundaria del Colegio Público María Parado de Bellido, a fin de determinar la influencia del referido programa en el fortalecimiento de la identidad cultural de los estudiantes. El tipo de investigación según los objetivos planteados en el presente estudio corresponde al de una investigación aplicada. Se desarrolló un nivel de investigación mixto (descriptivo-correlacional). Con respecto al diseño de la investigación fue determinado como cuasi experimental de carácter transversal. Se ha concluido que la aplicación del Programa de Valoración del Centro Histórico del Rímac influye positiva y significativamente en el fortalecimiento de la Identidad Cultural en las alumnas de tercer año de educación secundaria de la Institución Educativa María Parado de Bellido

SMALL ORGAN4 Is a Ribosome Biogenesis Factor Involved in 5.8S Ribosomal RNA Maturation

Ribosome biogenesis is crucial for cellular metabolism and has important implications for disease and aging. Human (Homo sapiens) glioma tumor-suppressor candidate region gene2 (GLTSCR2) and yeast (Saccharomyces cerevisiae) Nucleolar protein53 (Nop53) are orthologous proteins with demonstrated roles as ribosome biogenesis factors; knockdown of GLTSCR2 impairs maturation of 18S and 5.8S ribosomal RNAs (rRNAs), and Nop53 is required for maturation of 5.8S and 25S rRNAs. Here, we characterized SMALL ORGAN4 (SMO4), the most likely ortholog of human GLTSCR2 and yeast Nop53 in Arabidopsis (Arabidopsis thaliana). Loss of function of SMO4 results in a mild morphological phenotype; however, we found that smo4 mutants exhibit strong cytological and molecular phenotypes: nucleolar hypertrophy and disorganization, overaccumulation of 5.8S and 18S rRNA precursors, and an imbalanced 40S:60S ribosome subunit ratio. Like yeast Nop53 and human GLTSCR2, Arabidopsis SMO4 participates in 5.8S rRNA maturation. In yeast, Nop53 cooperates with mRNA transport4 (Mtr4) for 5.8S rRNA maturation. In Arabidopsis, we found that SMO4 plays similar roles in the 5.8S rRNA maturation pathway than those described for MTR4. However, SMO4 seems not to participate in the degradation of by-products derived from the 5′-external transcribed spacer (ETS) of 45S pre-rRNA, as MTR4 does

¿Resistencia en el acné? Un metaanálisis a propósito de la controversia

ResumenAntecedentesEl acné es una de las afecciones dermatológicas con mayor incidencia a nivel mundial; su origen es multifactorial y, por lo tanto, su tratamiento puede ser complejo. Propionibacterium acnes tiene un papel primordial en la inflamación de esta dermatosis y para su tratamiento se usan antibióticos tópicos; entre los principales se encuentran eritromicina y clindamicina, en los que se ha documentado una amplia resistencia bacteriana, lo que genera controversia respecto a su uso. Por este motivo se presenta un metaanálisis de las publicaciones de los últimos 10 años para confirmar esta hipótesis.Material y métodosEn la literatura de los últimos 10 años se buscaron artículos sobre resultados de cultivos con antibiograma de pacientes con acné. Se realizaron búsquedas tipo MeSH con los términos «acne vulgaris», «Propionibacterium acnes», «topical administration», «treatment», «erythromycin», «clindamycin», «nadifloxacin», «antibacterial agent», «bacterial drug resistance», en los metabuscadores PubMed, Ovid, EBSCO, Cochrane, ScienceDirect y ClinicalKey.ResultadosSe encontraron 13 artículos que cumplieron con los criterios de inclusión. La razón de momios promedio (OR 1.24, IC 95%) de los artículos demostró una ligera tendencia hacia la resistencia de Propionibacterium acnes.ConclusionesSe confirma el aumento en la resistencia bacteriana de Propionibacterium acnés a eritromicina y clindamicina tópica, por lo que recomendamos el uso de estos antibióticos combinados en casos selectos por periodos cortos y en combinación con peróxido de benzoilo, para obtener el mejor resultado clínico en los pacientes con Acne vulgaris.AbstractBackgroundAcne is one of the dermatological pathologies with the highest incidence around the world. It is a multifactorial disease and its treatment can be complex. Propionibacterium acnes play a key role in the inflammation of this dermatosis. Topical antibiotics, including mainly erythromycin and clindamycin, have been used, but there is controversy over their use due to the widely documented bacterial resistance. For this reason a meta-analysis of the publications over the past 10 years is presented in order to confirm this hypothesis.Material and methodsA search was made of the publications over the past 10 years that included the results of antibiogams of patients with acne. MeSH type searches were performed with the terms “acne vulgaris”, “Propionibacterium acnes”, “topical administration”, “treatment”, “erythromycin”, “clindamycin”, “nadifloxacin”, “antibacterial agent”, “bacterial drug resistance” in PubMed, Ovid, EBSCO, Cochrane, ScienceDirect and ClinicalKey meta-searches.ResultsA total of 13 articles were found that met the inclusion criteria. The mean odds ratio (OR 1.24, 95% CI) of the articles showed a slight tendency toward resistance of Propionibacterium acnes.ConclusionsAn increase in bacterial resistance to topical erythromycin and clindamycin can be confirmed, thus the use of these antibiotics is recommended in selective cases for short periods, and in combination with benzoyl peroxide for the best clinical outcome in patients with acne vulgaris

The photophysics of nitrocarbazoles studied by using spectroscopic, photoacoustic and luminescence techniques

The photophysical behaviour of 1-nitrocarbazol and 3-nitrocarbazol in different organic solvents has been studied by using spectroscopic, luminescence and photoacoustic techniques. Absorption spectra and triplet state transient spectra were recorded and formation quantum yields and lifetimes determined. Phosphorescence emission at 77 K and laser induced luminescence in acetonitrile solution at 298 K for the nitrocarbazoles were studied. Results are discussed in terms of the optimized structure of 1-nitrocarbazole and 3-nitrocarbazole and compared with that of carbazole. The nitro group attached to the carbazole moiety induces important changes in the photophysical behavior of those compounds

Next-generation forward genetic screens: using simulated data to improve the design of mapping-by-sequencing experiments in Arabidopsis

Forward genetic screens have successfully identified many genes and continue to be powerful tools for dissecting biological processes in Arabidopsis and other model species. Next-generation sequencing technologies have revolutionized the time-consuming process of identifying the mutations that cause a phenotype of interest. However, due to the cost of such mapping-by-sequencing experiments, special attention should be paid to experimental design and technical decisions so that the read data allows to map the desired mutation. Here, we simulated different mapping-by-sequencing scenarios. We first evaluated which short-read technology was best suited for analyzing gene-rich genomic regions in Arabidopsis and determined the minimum sequencing depth required to confidently call single nucleotide variants. We also designed ways to discriminate mutagenesis-induced mutations from background Single Nucleotide Polymorphisms in mutants isolated in Arabidopsis non-reference lines. In addition, we simulated bulked segregant mapping populations for identifying point mutations and monitored how the size of the mapping population and the sequencing depth affect mapping precision. Finally, we provide the computational basis of a protocol that we already used to map T-DNA insertions with paired-end Illumina-like reads, using very low sequencing depths and pooling several mutants together; this approach can also be used with single-end reads as well as to map any other insertional mutagen. All these simulations proved useful for designing experiments that allowed us to map several mutations in Arabidopsis

A New Under-Sampling Method to Face Class Overlap and Imbalance

Class overlap and class imbalance are two data complexities that challenge the design of effective classifiers in Pattern Recognition and Data Mining as they may cause a significant loss in performance. Several solutions have been proposed to face both data difficulties, but most of these approaches tackle each problem separately. In this paper, we propose a two-stage under-sampling technique that combines the DBSCAN clustering algorithm to remove noisy samples and clean the decision boundary with a minimum spanning tree algorithm to face the class imbalance, thus handling class overlap and imbalance simultaneously with the aim of improving the performance of classifiers. An extensive experimental study shows a significantly better behavior of the new algorithm as compared to 12 state-of-the-art under-sampling methods using three standard classification models (nearest neighbor rule, J48 decision tree, and support vector machine with a linear kernel) on both real-life and synthetic databases

Loss of function of Arabidopsis microRNA-machinery genes impairs fertility, and has effects on homologous recombination and meiotic chromatin dynamics

MicroRNAs (miRNAs) are ~22-nt single-stranded noncoding RNAs with regulatory roles in a wide range of cellular functions by repressing eukaryotic gene expression at a post-transcriptional level. Here, we analyzed the effects on meiosis and fertility of hypomorphic or null alleles of the HYL1, HEN1, DCL1, HST and AGO1 genes, which encode miRNA-machinery components in Arabidopsis. Reduced pollen and megaspore mother cell number and fertility were shown by the mutants analyzed. These mutants also exhibited a relaxed chromatin conformation in male meiocytes at the first meiotic division, and increased chiasma frequency, which is likely to be due to increased levels of mRNAs from key genes involved in homologous recombination. The hen1-13 mutant was found to be hypersensitive to gamma irradiation, which mainly causes double-strand breaks susceptible to be repaired by homologous recombination. Our findings uncover a role for miRNA-machinery components in Arabidopsis meiosis, as well as in the repression of key genes required for homologous recombination. These genes seem to be indirect miRNA targets

Transformative learning experience among nursing students with patients acting as teachers: Mixed methods, non-randomized, single-arm study

Expert patient; Nursing education; People living with HIVPaciente experto; Educación en enfermería; Personas que viven con el VIHPacient expert; Educació en infermeria; Persones que viuen amb el VIHAim To examine the effects of expert HIV patients acting as teachers to Spanish nursing students both on their HIV-related knowledge, attitudes and practices and on their approach to the care model as well as to explore their learning experience. Design Non-randomized, single-arm study with quantitative before and after measurements and qualitative data. Methods The intervention consisted of five 90-min workshops led by two women living with HIV. Thirty-four nursing students participated, and quantitative and qualitative data were gathered from February to June 2018. We used the Patient-Practitioner Orientation Scale (PPOS) and the KAP questionnaire on HIV/AIDS to collect quantitative data. Results Statistically significant differences were found in the global score for care orientation and its two dimensions, caring and sharing. About the changes resulting from the workshops, the quantitative results—more patient-centred care perception and better attitudes towards people living with HIV—match the qualitative findings in all the aspects studied, except in sharing. Conclusion Incorporating expert patients as teachers in the nursing bachelor's degree resulted in more patient-centred care and improved knowledge, attitudes and practices. The workshops conducted by qualified expert patients showed transformative learning power, as the participants improved professional and personal aspects.This study was supported by a Community Grant ‘Cuidados de, por y para las personas que viven con VIH. personas que viven con VIH como docentes en la formación de estudiantes de enfermería’ from Gilead Sciences, S.L., Spain, in 2017 Community Grants & Donations Program