Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis.

We and others have previously shown that the SARS-CoV-2 accessory protein ORF6 is a powerful antagonist of the interferon (IFN) signaling pathway by directly interacting with Nup98-Rae1 at the nuclear pore complex (NPC) and disrupting bidirectional nucleo-cytoplasmic trafficking. In this study, we further assessed the role of ORF6 during infection using recombinant SARS-CoV-2 viruses carrying either a deletion or a well characterized M58R loss-of-function mutation in ORF6. We show that ORF6 plays a key role in the antagonism of IFN signaling and in viral pathogenesis by interfering with karyopherin(importin)-mediated nuclear import during SARS-CoV-2 infection both in vitro, and in the Syrian golden hamster model in vivo. In addition, we found that ORF6-Nup98 interaction also contributes to inhibition of cellular mRNA export during SARS-CoV-2 infection. As a result, ORF6 expression significantly remodels the host cell proteome upon infection. Importantly, we also unravel a previously unrecognized function of ORF6 in the modulation of viral protein expression, which is independent of its function at the nuclear pore. Lastly, we characterized the ORF6 D61L mutation that recently emerged in Omicron BA.2 and BA.4 and demonstrated that it is able to disrupt ORF6 protein functions at the NPC and to impair SARS-CoV-2 innate immune evasion strategies. Importantly, the now more abundant Omicron BA.5 lacks this loss-of-function polymorphism in ORF6. Altogether, our findings not only further highlight the key role of ORF6 in the antagonism of the antiviral innate immune response, but also emphasize the importance of studying the role of non-spike mutations to better understand the mechanisms governing differential pathogenicity and immune evasion strategies of SARS-CoV-2 and its evolving variants. ONE SENTENCE SUMMARYSARS-CoV-2 ORF6 subverts bidirectional nucleo-cytoplasmic trafficking to inhibit host gene expression and contribute to viral pathogenesis.

Beamforming and holography image formation methods: an analytic study.

Beamforming and holographic imaging procedures are widely used in many applications such as radar sensing, sonar, and in the area of microwave medical imaging. Nevertheless, an analytical comparison of the methods has not been done. In this paper, the Point Spread Functions pertaining to the two methods are analytically determined. This allows a formal comparison of the two techniques, and to easily highlight how the performance depends on the configuration parameters, including frequency range, number of scatterers, and data discretization. It is demonstrated that the beamforming and holography basically achieve the same resolution but beamforming requires a cheaper (less sensors) configuration..

[Rate of human papillomavirus infection in rural areas diagnosed by direct visualization with acetic acid and lugol]. / Tasa de infección por virus del papiloma humano diagnosticada mediante visualización directa con ácido acético y lugol (en pacientes del área rural).

BACKGROUND: Infection by HPV is a major global health problem and the main risk factor for cervical cancer with high morbidity and mortality. Simple diagnostic methods, such as visual inspection with the naked eye of the cervix with acetic acid application 5% (VAT) or solution of iodine (tincture of iodine) are simple to detect early lesions, sensitivity varies from 87 to 99% and specificity varies from 23 to 87%. OBJECTIVE: To find the proportion of infection by human papillomavirus in a population of extreme poverty. MATERIAL AND METHOD: Linear, observational and descriptive pilot study was done in patients of marginalized communities in extreme poverty in Chiapas (Mexico), from 1 to 30 November 2013. The existence of acetowhite lesions suggestive of virus was verified human papillomavirus, and medical history of all patients was formed for the incidence of risk factors. RESULTS: 214 women with age limits of 19 and 78 years, median age of 37 years were studied. Of the total, 66 (31%) had acetowhite lesions consistent with human papillomavirus at the time of the study. CONCLUSIONS: Marginalized populations have a higher risk of infection with human papillomavirus, consequently high rate of progression to cervical cancer due to sociodemographic characteristics, risk factors and lack of resources in health. Diagnostic tests like the simple display with acetic acid are ideal for people such as this.

Gemcitabine plus paclitaxel as first-line chemotherapy for patients with advanced breast cancer.

OBJECTIVES: To assess the efficacy and tolerability of gemcitabine and paclitaxel as first-line treatment in advanced breast cancer. METHODS: Patients with histologically confirmed metastatic or metastatic plus locally advanced breast cancer received gemcitabine 1,200 mg/m(2) on days 1 and 8 and paclitaxel 175 mg/m(2) on day 1 every 21 days for 8 cycles. RESULTS: From December 1999 to August 2001, 45 patients, with a median age of 53.5 years (range, 22-77), received a total of 260 cycles. All were assessable for response and toxicity. Twenty-seven patients had prior adjuvant therapy. Hormonal receptor status was positive in 31.1% and negative in 40.0% of patients. Main metastatic sites included soft tissue (62.2%) and lung (53.3%). The objective response rate was 66.7%; complete response, 22.2%; partial response, 44.4%; stable disease, 15.6%; progressive disease, 17.8%. Median duration of response was 18 months and median time to tumor progression was 11 months. Grade 3/4 leukopenia, neutropenia, and thrombocytopenia developed in 13.3% of patients, and 15.5% developed grade 3/4 mucositis. No treatment-related deaths occurred. Median overall survival was 19 months. CONCLUSIONS: Gemcitabine plus paclitaxel is an active combination with a favorable toxicity profile as first-line treatment for patients with advanced breast cancer.

Preparación de Tiras Reactivas para Análisis de Orina

De la investigación realizada en 100 muestras patológicas de orina empleando método químico diagnóstico, tira reactiva marca combi y tira reactiva elaborada por nosotras, se desprenden las siguientes deducciones: Se ha comprobado que las tiras reactivas preparadas por nosotras presentan un 90 por ciento de igual exactitud y precisión que las tiras combi. Las tiras combi, siendo más económicas por lo que están en condiciones de reemplazarlas. Las tiras reactivas de un solo parámetro. (glucosa) pueden ser destinadas al control de pacientes con glucosuria. Consideramos que el profesional químico farmacéutico está capacitado para elaborar reactivos químicos destinados a la fabricación de tiras reactivas para ser utilizadas en los análisis de orina.