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The recent pandemic was caused by the emergence of a new human pathogen, SARS-CoV-2. While the rapid development of many vaccines provided an end to the immediate crisis, there remains an urgent need to understand more about this new virus and what constitutes a beneficial immune response in terms of successful resolution of infection. Indeed, this is key for development of vaccines that provide long lasting protective immunity. The interferon lambda (IFNL) family of cytokines are produced early in response to infection and are generally considered anti-viral and beneficial. However, data regarding production of IFNL cytokines in COVID-19 patients is highly variable, and generally from underpowered studies. In this study, we measured all three IFNL1, IFNL2 and IFNL3 cytokines in plasma from a well characterised, large COVID-19 cohort (n=399) that included good representation from patients with a more indolent disease progression, and hence a beneficial immune response. While all three cytokines were produced, they differed in both the frequency of expression in patients, and the levels produced. IFNL3 was produced in almost all patients but neither protein level nor IFNL3/IFNL4 SNPs were associated with clinical outcome. In contrast, both IFNL1 and IFNL2 levels were significantly lower, or absent, in plasma of patients that had a more severe disease outcome. These data are consistent with the concept that early IFNL1 and IFNL2 cytokine production is protective against SARS-CoV-2 infection.

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Translation of mRNAs that encode peptide sequences with consecutive prolines (polyproline) requires the conserved and essential elongation factor eIF5A to facilitate the formation of peptide bonds. It has been shown that, upon eIF5A depletion, yeast ribosomes stall in polyproline motifs, but also in tripeptide sequences that combine proline with glycine and charged amino acids. Mammalian collagens are enriched in putative eIF5A-dependent Pro-Gly-containing tripeptides. Here, we show that depletion of active eIF5A in mouse fibroblasts reduced collagen type I α1 chain (Col1a1) content, which concentrated around the nuclei. Moreover, it provoked the upregulation of endoplasmic reticulum (ER) stress markers, suggesting retention of partially synthesized collagen 1 (Col1) in the ER. We confirmed that eIF5A is needed for heterologous collagen synthesis in yeast and, using a double luciferase reporter system, showed that eIF5A depletion interrupts translation at Pro-Gly collagenic motifs. A dramatically lower level of Col1a1 protein was also observed in functional eIF5A-depleted human hepatic stellate cells treated with the profibrotic cytokine TGF-ß1. In sum, our results show that collagen expression requires eIF5A and imply its potential as a target for regulating collagen production in fibrotic diseases.

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The adjustment of transcription and translation rates to the changing needs of cells is of utmost importance for their fitness and survival. We have previously shown that the global transcription rate for RNA polymerase II in budding yeast Saccharomyces cerevisiae is regulated in relation to cell volume. Total mRNA concentration is constant with cell volume since global RNApol II-dependent nascent transcription rate (nTR) also keeps constant but mRNA stability increases with cell size. In this paper, we focus on the case of rRNA and RNA polymerase I. Contrarily to that found for RNA pol II, we detected that RNA polymerase I nTR increases proportionally to genome copies and cell size in polyploid cells. In haploid mutant cells with larger cell sizes, the rDNA repeat copy number rises. By combining mathematical modeling and experimental work with the large-size cln3 strain, we observed that the increasing repeat copy number is based on a feedback mechanism in which Sir2 histone deacetylase homeostatically controls the amplification of rDNA repeats in a volume-dependent manner. This amplification is paralleled with an increase in rRNA nTR, which indicates a control of the RNA pol I synthesis rate by cell volume.

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El fibroma perifolicular es una entidad benigna poco frecuente: se caracteriza por ser una lesión proliferante deribada de la vaina perifolicular. Topográficamente es usual su aparición en la cabeza, presentándose como pápulas o nódulos de aspecto cupular único o múltiples. El diagnóstico recae en el estudio histopatológico, donde se observa tejido fibroso alrededor del folículo piloso. Se presenta un caso inusual en un paciente de 6 años con múltiples pápulas asintomáticas en cuello, motivo por el cual acudió a la consulta.

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Most cells divide symmetrically into two approximately identical cells. There are many examples, however, of asymmetric cell division that can generate sibling cell size differences. Whereas physical asymmetric division mechanisms and cell fate consequences have been investigated, the specific problem caused by asymmetric division at the transcription level has not yet been addressed. In symmetrically dividing cells the nascent transcription rate increases in parallel to cell volume to compensate it by keeping the actual mRNA synthesis rate constant. This cannot apply to the yeast Saccharomyces cerevisiae, where this mechanism would provoke a never-ending increasing mRNA synthesis rate in smaller daughter cells. We show here that, contrarily to other eukaryotes with symmetric division, budding yeast keeps the nascent transcription rates of its RNA polymerases constant and increases mRNA stability. This control on RNA pol II-dependent transcription rate is obtained by controlling the cellular concentration of this enzyme.

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Although an increasing number of horizontal gene transfers have been reported in eukaryotes, experimental evidence for their adaptive value is lacking. Here, we report the recent transfer of a 158-kb genomic region between Torulaspora microellipsoides and Saccharomyces cerevisiae wine yeasts or closely related strains. This genomic region has undergone several rearrangements in S. cerevisiae strains, including gene loss and gene conversion between two tandemly duplicated FOT genes encoding oligopeptide transporters. We show that FOT genes confer a strong competitive advantage during grape must fermentation by increasing the number and diversity of oligopeptides that yeast can utilize as a source of nitrogen, thereby improving biomass formation, fermentation efficiency, and cell viability. Thus, the acquisition of FOT genes has favored yeast adaptation to the nitrogen-limited wine fermentation environment. This finding indicates that anthropic environments offer substantial ecological opportunity for evolutionary diversification through gene exchange between distant yeast species.

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Antecedentes. La blastomicosis es una enfermedad infecciosa granulomatosa, causada por el hongo dimorfo Blastomyces dermatitidis. Predomina en Estados Unidos de América, y en México solo se han reportado 2 casos sistémicos importados. La forma primaria cutánea es la presentación clínica menos frecuente de la enfermedad y ocurre después de la inoculación del hongo por traumatismo. Objetivos. Se presenta el caso de un hombre de 54 años de edad, originario de Guadalajara, México, y residente en Chicago, Estados Unidos. Presentaba en la región frontal y surco nasogeniano derecho 2 nódulos verrugosos de 8mm de diámetro de 4 semanas de evolución. Métodos. Se realizó un estudio histopatológico (tinciones de hematoxilina-eosina, Gomori-Grocott y ácido peryódico de Schiff), además, estudio micológico (directo con KOH y cultivos en agar Sabouraud y micobiótico). Además, se realizaron otros estudios que descartaron afección sistémica. Resultados. La biopsia mostró una dermis con infiltrado inflamatorio compuesto por linfocitos, neutrófilos, histiocitos y células gigantes multinucleadas, y escasas levaduras monogemantes con base ancha y rodeadas por un halo. Al examen directo con KOH, se observaron levaduras monogemantes de 8 a 10mm de diámetro de B. dermatitidis. En el cultivo a 35°C creció una colonia blanca, plegada que, con el tiempo, se tornó amarillenta y cerebriforme. Resultados. Se indicó tratamiento con itraconazol a dosis de 200mg/d durante 2 meses con curación clínica y micológica. Conclusiones. El caso presentado podría ser el primero importado en México donde la blastomicosis se presenta solo con lesiones cutáneas y sin compromiso sistémico(AU)

Background. Blastomycosis is a granulomatous infectious disease. It is caused by the dimorphus fungus Blastomyces dermatitidis. It predominates in the United States of America, but in Mexico two systemic imported cases have been reported. Cutaneous primary blastomycosis is a rare clinical presentation, which occurs after traumatic inoculation of the fungus. Objectives. We present a case of a 54 year old male, born in Guadalajara, Mexico, and living in Chicago, USA, who had two verrucous nodules (8mm in diameter) on the forehead and right nasogenian fold, of 4 weeks progression. Methods. We made a histopathological study (hematoxylin and eosin, Gomori Groccot and periodic acid-Schiff stains) and mycology studies (direct microscopic examination, Sabouraud and mycobiotic agar cultures). Multiple studies were made with no evidence of systemic spread. Results. Biopsy showed a dermal inflammatory infiltrate made up of lymphocytes, neutrophils, histiocytes and multinucleated giant cells. A few large, haloed, broad-based budding yeasts were also observed. Direct examination with KOH revealed broad-based budding yeasts, 10ìm in diameter. Culture at 35°C yielded a white, pleated colony, which changed into a yellowish cerebriform. Multiple studies were made with no evidence of systemic spread. Results. Itraconazole 200mg qd PO was given over a 2 month period, with a complete clinical and mycological response. Conclusions. This is the first imported case in Mexico of blastomycosis with cutaneous lesions without systemic involvement(AU)

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BACKGROUND: Blastomycosis is a granulomatous infectious disease. It is caused by the dimorphus fungus Blastomyces dermatitidis. It predominates in the United States of America, but in Mexico two systemic imported cases have been reported. Cutaneous primary blastomycosis is a rare clinical presentation, which occurs after traumatic inoculation of the fungus. OBJECTIVES: We present a case of a 54 year old male, born in Guadalajara, Mexico, and living in Chicago, USA, who had two verrucous nodules (8mm in diameter) on the forehead and right nasogenian fold, of 4 weeks progression. METHODS: We made a histopathological study (hematoxylin and eosin, Gomori Groccot and periodic acid-Schiff stains) and mycology studies (direct microscopic examination, Sabouraud and mycobiotic agar cultures). Multiple studies were made with no evidence of systemic spread. RESULTS: Biopsy showed a dermal inflammatory infiltrate made up of lymphocytes, neutrophils, histiocytes and multinucleated giant cells. A few large, haloed, broad-based budding yeasts were also observed. Direct examination with KOH revealed broad-based budding yeasts, 10µm in diameter. Culture at 35°C yielded a white, pleated colony, which changed into a yellowish cerebriform. Multiple studies were made with no evidence of systemic spread. Itraconazole 200mg qd PO was given over a 2 month period, with a complete clinical and mycological response. CONCLUSIONS: This is the first imported case in Mexico of blastomycosis with cutaneous lesions without systemic involvement.

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El propósito de este estudio fue investigar si la profilaxis antibiótica en cirugía de terceros molares incluidos es efectiva para el control de la infección postquirúgica asociada a estos procedimientos. En la literatura se encuentran una gran variedad de opiniones acerca del uso de antibióticos. El antibiótico seleccionado para profilaxis fue amoxacilina utilizando una dosis de 1 gr. por vía oral, una hora antes del procedimienlo y 1 gr. seis horas después, en dos grupos de pacientes, uno de los cuales recibió el antibiótico y el otro un placebo. Se usaron los protocolos convencionales para la asepsia, antisepsia y esterilización del instrumental, así también como para el procedimiento quirúrgico, el cual fue efectuado por un cirujano maxilofacial. Los pacientes seleccionados fueron ASA I (Asociación americana de anestesiología), que no tuvieran ningún proceso infeccioso en cavidad oral y con aceptable higiene oral. El estudio fue triple ciego controlado; en donde el cirujano, el paciente ni el estadístico conocieron que medicamento se le dio al paciente. Todos los pacientes fueron controlados al quinto y décimo día del posoperatorio y tuvieron instrucciones de informar inmediatamente cualquier complicación. En caso de presentarse una infección se tomaría un cultivo con antibiograma para organismos aerobios y anaerobios y mientras se reciben los resultados se iniciaría tratamiento con clindamicina 300mg. vía oral cada 6 horas. Esta investigación fue aprobada por el comité de ética en humanos de la facultad de salud de la Universidad del Valle y todos los pacientes llenaron un formato de consentimiento.

The purpose of this study was to investigate if antibiotic prevention in surgery of third molars included is effective for the control of postsurgery infection. ln the literature, there are a great variety of opinions about the use of antibiotics. In this study, the selected antibiotic was amoxacilina 1 gr. orally given one hour before the procedure and six hours later. There were two groups of patients, one of those which received the antibiotic and the other the placebo. Conventional protocols were used for the asepsis, antisepsis and sterilization of the instrumental, likewise for the surgical procedure made by a maxillofacial surgeon. Selected patients were classified ASA I (American Association of anaesthesiology) that don't have any infectious process in oral cavity and acceptable oral hygiene. The study design was a triple blind controlled where the surgeon, the patient or the statisticon knew wich medication was given to the patient. All the patients were controlled to the fifth and tenth day possurgery. Patients were instructed to inform the doctor arised any complication immediately. In the event of being presented an infection, it was recomended cultivation and antibiogram for aerobic and anaerobic and while the results are received treatment with clindamicina. The investigation was approved by the ethics committee in human health at the University of Valley and all the patients filled a consent formal. 102 patients were studied (49 received antibiotic and 53 placebo) in a period from September 1, 1.998 to September 1, 2.000. No patient resulted infected. The conclusion of the investigation therefore was that the use of antibiotics is not required for the surgery of third included molars.

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