Transcriptional Profiles of California Sea Lion Peripheral NK and CD+8 T Cells Reflect Ecological Regionalization and Infection by Oncogenic Viruses

The California sea lion is one of the few wild mammals prone to develop cancer, particularly urogenital carcinoma (UGC), whose prevalence is currently estimated at 25% of dead adult sea lions stranded along the California coastline. Genetic factors, viruses and organochlorines have been identified as factors that increase the risk of occurrence of this pathology. Given that no cases of UGC have as yet been reported for the species along its distribution in Mexican waters, the potential relevance of contaminants for the development of urogenital carcinoma is highlighted even more as blubber levels of organochlorines are more than two orders of magnitude lower in the Gulf of California and Mexican Pacific than in California. In vitro studies have shown that organochlorines can modulate anti-viral and tumor-surveillance activities of NK and cytotoxic T-cells of marine mammals, but little is known about the activity of these effectors in live, free-living sea lions. Here, we examine leukocyte transcriptional profiles of free-ranging adult California sea lions for eight genes (Eomes, Granzyme B, Perforin, Ly49, STAT1, Tbx21, GATA3, and FoxP3) selected for their key role in anti-viral and tumor-surveillance, and investigate patterns of transcription that could be indicative of differences in ecological variables and exposure to two oncogenic viruses: sea lion type one gammaherpesvirus (OtHV-1) and sea lion papillomavirus type 1 (ZcPV-1) and systemic inflammation. We observed regional differences in the expression of genes related to Th1 responses and immune modulation, and detected clear patterns of differential regulation of gene expression in sea lions infected by genital papillomavirus compared to those infected by genital gammaherpesvirus or for simultaneous infections, similar to what is known about herpesvirus and papillomavirus infections in humans. Our study is a first approach to profile the transcriptional patterns of key immune effectors of free-ranging California sea lions and their association with ecological regions and oncogenic viruses. The observed results add insight to our understanding of immune competence of marine mammals, and may help elucidate the marked difference in the number of cases of urogenital carcinoma in sea lions from US waters and other areas of their distribution

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Descripción: El curso International Business es un curso de línea de carrera de Administración y Negocios Internacionales de carácter teórico-práctico dirigido a los estudiantes del tercer ciclo con el objetivo de brindar una visión global y actual del entorno de los negocios el cual responde a un enfoque moderno de la administración estratégica de las empresas. Propósito: El curso International Business es relevante para los estudiantes porque busca desarrollar las capacidades que le permitirán al futuro profesional formular proyectos internacionales de negocios en un contexto global según las nuevas tendencias de Geomundo teniendo en cuenta los aspectos culturales, sociales, económicos, políticos, legales, jurídicos y financieros del dinámico entorno internacional los cuales impactan en el desempeño de las organizaciones donde ejercerá laboralmente, teniendo como prerrequisito el curso 1Introduction to International Business. El curso contribuye directamente al desarrollo de la competencia específica de Formulación de Proyectos Internacionales del nivel 1

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Climatic anomaly affects the immune competence of California sea lions

<div><p>The past decades have been characterized by a growing number of climatic anomalies. As these anomalies tend to occur suddenly and unexpectedly, it is often difficult to procure empirical evidence of their effects on natural populations. We analysed how the recent sea surface temperature (SST) anomaly in the northeastern Pacific Ocean affects body condition, nutritional status, and immune competence of California sea lion pups. We found that pup body condition and blood glucose levels of the pups were lower during high SST events, although other biomarkers of malnutrition remained unchanged, suggesting that pups were experiencing early stages of starvation. Glucose-dependent immune responses were affected by the SST anomaly; specifically, pups born during high SST events had lower serum concentrations of IgG and IgA, and were unable to respond to an immune challenge. This means that not only were pups that were born during the SST anomaly less able to synthesize protective antibodies; they were also limited in their ability to respond rapidly to nonspecific immune challenges. Our study provides empirical evidence that atypical climatic conditions can limit energetic reserves and compromise physiological responses that are essential for the survival of a marine top predator.</p></div

Sea surface temperature anomaly (°C) in the northeastern Pacific Ocean.

<p>Panels show the average of values recorded April 1^st to July 31^st for (<b>A</b>) 2012, (<b>B</b>) 2013, (<b>C</b>) 2014, and (<b>D</b>) 2015. The location of the San Benito Archipelago is indicated within the square. Images provided by the NOAA/ESRL Physical Sciences Division, Boulder Colorado from their Web site at <a href="http://www.esrl.noaa.gov/psd/" target="_blank">http://www.esrl.noaa.gov/psd/</a>. The plots were created by using data collected by the NCEP/NCAR Reanalysis Project [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179359#pone.0179359.ref033" target="_blank">33</a>].</p

White blood cell counts of California sea lion, <i>Zalophus californianus</i>, pups that differed between those born during normal (2012) and atypical (2014 and 2015) sea surface temperature conditions.

<p>A) Basophils, B) Band neutrophils, C) Hypersegmented neutrophils.</p

Skin-fold thickness in response to PHA challenge.

<p>Response to PHA in California sea lion, <i>Zalophus californianus</i>, pups born during normal (2012) and atypical (2015) sea surface temperature conditions.</p

Serum antibody levels of California sea lion, <i>Zalophus californianus</i>, pups born under normal (2012) and atypical (2014 and 2015) sea surface temperature conditions.

<p>A) IgG, B) IgA, C) IgM.</p