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Small Ruminant Lentiviruses (SRLVs) are widespread in many countries and cause economically relevant, slow, and persistent diseases in sheep and goats. Monitoring the genetic diversity of SRLVs is useful to improve the diagnostic tools used in the eradication programs. In this study, SRLVs detected in Spanish Assaf sheep with different grades of lymphoproliferative mastitis were sequenced. Genetic characterization showed that most samples belonged to type A and were closer to Spanish SRLV isolates previously classified as A2/A3. Four samples belonged to subtype B2 and showed higher homology with Italian B2 strains than with Spanish B2 isolates. Amino acid sequences of immuno-dominant epitopes in the gag region were very conserved while more alterations were found in the LTR sequences. No significant correlations were found between grades of mastitis and alterations in the sequences although samples with similar histological features were phylogenetically closer to each other. Broader genetic characterization surveys in samples with different grades of SRLV-lesions are required for evaluating potential correlations between SRLV sequences and the severity of diseases.

This work summarizes the mortality cases of twenty-five free-ranging Eurasian wild brown bears (Ursus arctos arctos) from the Cantabrian mountain range submitted for necropsy in Asturias and Castilla y León (northwestern Spain) from 1998 to 2018. Mortality cases were classified both caused by (i) “non-human intervention” or “human intervention” causes and based on (ii) “non-infectious” or “infectious” etiology. In four cases (16%) it was not possible to determine the cause of death due to the inadequate preservation of collected specimens or insufficient tissue availability. Based on “non-human intervention” or “human intervention” causes, fourteen of the 21 (66.7%) brown bears died as a consequence of “non-human intervention” due to traumatic lesions (fights, unknown traumas or infanticide), infectious canine hepatitis, neoplasia or mushroom poisoning. In contrast, seven (33.3%) brown bears died by “human intervention” due to illegal hunting (shooting or snare), handling (during transit in an attempt to reintroduce a bear back into the wild) or strychnine poisoning. Based on “non-infectious” or “infectious” etiology, twelve of the 21 (57.1%) brown bears died due to “non-infectious” causes, namely traumatic lesions such as shooting, snare, fighting or infanticide, handling, strychnine poisoning, mushroom poisoning or neoplasia. The remaining nine (42.9%) animals died due to “infectious” diseases which included gangrenous myositis, infectious canine hepatitis or septicemia. In six of those cases traumatic lesions caused by non-human or human activities were complicated with bacterial infection (clostridiosis and septicemia) which finally caused the death of those animals. Additionally, exertional myopathy was observed in the handled animal and in one bear found in a snare. In a free-ranging population of Eurasian brown bear from the Cantabrian mountain range, main causes of death are attributed to non-human related traumatic lesions and infectious diseases (primary developed such as infectious canine hepatitis or secondary developed such as clostridiosis or septicemia) which is in contrast to previously reported data for other bear populations. These data are valuable and may help in the conservation and management of this recovering population.

Small Ruminant Lentiviruses (SRLVs) are widespread in many countries and cause economically relevant, slow, and persistent diseases in sheep and goats. Monitoring the genetic diversity of SRLVs is useful to improve the diagnostic tools used in the eradication programs. In this study, SRLVs detected in Spanish Assaf sheep with different grades of lymphoproliferative mastitis were sequenced. Genetic characterization showed that most samples belonged to type A and were closer to Spanish SRLV isolates previously classified as A2/A3. Four samples belonged to subtype B2 and showed higher homology with Italian B2 strains than with Spanish B2 isolates. Amino acid sequences of immuno-dominant epitopes in the gag region were very conserved while more alterations were found in the LTR sequences. No significant correlations were found between grades of mastitis and alterations in the sequences although samples with similar histological features were phylogenetically closer to each other. Broader genetic characterization surveys in samples with different grades of SRLV-lesions are required for evaluating potential correlations between SRLV sequences and the severity of diseases.

Various investigations have revealed that the promotion of cognitive and metacognitive strategies can improve reading comprehension and that when readers receive this type of instruction, they can use monitoring processes and regulation strategies adequately. The goal of this work is to analyze the effects of strategic and metacognitive instruction on reading comprehension processes and strategies, using the \"Aprender a Comprender\" [Learning to Understand] program. Instruction was carried out in the classroom by two teachers during six months. Ninety-four students participated, 49 from 5th grade and 45 from 6th grade. A pretest-intervention-posttest-follow-up design was used with a comparison group by grade. The analysis of variance shows an impact of the intervention and its differential maintenance in each grade. The 5th-grade intervention group scored higher than the comparison group in the reading comprehension test, both at posttest and at follow-up. The 6th-grade intervention group scored higher than the comparison group in the Planning scale, both at posttest and at follow-up. Textual strategy instruction favors reading comprehension and the progressive development of planning, which is necessary for supervision and regulation, and its effects are maintained over time.

SARS-CoV-2 is responsible for the development of coronavirus disease 2019 (COVID-19) in infected individuals, who can either exhibit mild symptoms or progress toward a life-threatening acute respiratory distress syndrome (ARDS). Exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. Here, we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood and lung of COVID-19 patients with different clinical severity in comparison with healthy individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Our results indicate that inflammatory transitional and nonclassical monocytes and CD1c+ conventional dendritic cells preferentially migrate from blood to lungs in patients with severe COVID-19. Thus, this study increases the knowledge of specific myeloid subsets involved in the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies for fighting SARS-CoV-2 infection.

The Interferon-Stimulated Gene 15 (ISG15) has a key role during viral infections, since it can modify and regulate the expression of proteins from the host and from viruses. Isg15 −/− mice are more susceptible to infectious diseases. ISG15 is induced by type I Interferons (IFN-I) and apart from defense against pathogens, it can also play an important function in cancer or immune-mediated inflammatory diseases. Previous studies reported that ISG15 expression is increased in post-synaptic dendritic cells (DCs) upon interaction with CD4 + T cells. However, data regarding the role of ISG15 in DCs are scarce. The present study assesses the function of ISG15 in DCs activation, migration and ability to mediate T cell activation using bone marrow-derived DCs (BMDCs) and stimulation with lipopolysaccharide (LPS). Activation of DCs was not impaired but tended to be lower in Isg15 -deficient mice, as observed by reduced CD40 induction in Isg15 −/− BMDCs. Isg15 −/− BMDCs induced less proliferation and Granzyme B expression in co-cultured CD8 + T cells. Interestingly, Isg15 −/− BMDCs secreted reduced levels of the pro-inflammatory cytokines IL-1β and IL-12 upon LPS stimulation. Mechanistically, our data suggest that ISG15 regulates Caspase-1 activity in DCs leading to lower IL-1 β secretion. In conclusion, this study reveals an essential role for ISG15 modulating DCs inflammatory activity and raises new questions regarding the specific mechanisms of how this protein regulates innate immune responses.

Tyrosine kinase 2 (TYK2) is involved in type I interferon (IFN-I) signaling through IFN receptor 1 (IFNAR1). This signaling pathway is crucial in the early antiviral response and remains incompletely understood on B cells. Therefore, to understand the role of TYK2 in B cells, we studied these cells under homeostatic conditions and following in vitro activation using Tyk2 -deficient ( Tyk2 −/− ) mice. Splenic B cell subpopulations were altered in Tyk2 −/− compared to wild type (WT) mice. Marginal zone (MZ) cells were decreased and aged B cells (ABC) were increased, whereas follicular (FO) cells remained unchanged. Likewise, there was an imbalance in transitional B cells in juvenile Tyk2 −/− mice. RNA sequencing analysis of adult MZ and FO cells isolated from Tyk2 −/− and WT mice in homeostasis revealed altered expression of IFN-I and Toll-like receptor 7 (TLR7) signaling pathway genes. Flow cytometry assays corroborated a lower expression of TLR7 in MZ B cells from Tyk2 −/− mice. Splenic B cell cultures showed reduced proliferation and differentiation responses after activation with TLR7 ligands in Tyk2 −/− compared to WT mice, with a similar response to lipopolysaccharide (LPS) or anti-CD40 + IL-4. IgM, IgG, IL-10 and IL-6 secretion was also decreased in Tyk2 −/− B cell cultures. This reduced response of the TLR7 pathway in Tyk2 −/− mice was partially restored by IFNα addition. In conclusion, there is a crosstalk between TYK2 and TLR7 mediated by an IFN-I feedback loop, which contributes to the establishment of MZ B cells and to B cell proliferation and differentiation.

Increased recruitment of transitional and non-classical monocytes in the lung during SARS-CoV-2 infection is associated with COVID-19 severity. However, whether specific innate sensors mediate the activation or differentiation of monocytes in response to different SARS-CoV-2 proteins remain poorly characterized. Here, we show that SARS-CoV-2 Spike 1 but not nucleoprotein induce differentiation of monocytes into transitional or non-classical subsets from both peripheral blood and COVID-19 bronchoalveolar lavage samples in a NFκB-dependent manner, but this process does not require inflammasome activation. However, NLRP3 and NLRC4 differentially regulated CD86 expression in monocytes in response to Spike 1 and Nucleoprotein, respectively. Moreover, monocytes exposed to Spike 1 induce significantly higher proportions of Th1 and Th17 CD4 + T cells. In contrast, monocytes exposed to Nucleoprotein reduce the degranulation of CD8 + T cells from severe COVID-19 patients. Our study provides insights in the differential impact of innate sensors in regulating monocytes in response to different SARS-CoV-2 proteins, which might be useful to better understand COVID-19 immunopathology and identify therapeutic targets. The immunobiology regulating the contribution of monocytes to severe COVID-19 immunopathology are not fully understood. Here the authors show that SARS-CoV-2 S1 and NP proteins differentially promote NLRP3/NLRC4 inflammasome activity, differentiation, and T cell-priming function of monocytes.

Vegetable oils such as palm oil (enriched in saturated fatty acids, SFA) and high-oleic-acid sunflower oil (HOSO, containing mainly monounsaturated fatty acids, MUFA) have emerged as the most common replacements for trans-fats in the food industry. The aim of this study is to analyze the impact of SFA and MUFA-enriched high-fat (HF) diets on endothelial function, vascular remodeling, and arterial stiffness compared to commercial HF diets. Five-week-old male C57BL6J mice were fed a standard (SD), a HF diet enriched with SFA (saturated oil-enriched Food, SOLF), a HF diet enriched with MUFA (unsaturated oil-enriched Food, UOLF), or a commercial HF diet for 8 weeks. Vascular function was analyzed in the thoracic aorta. Structural and mechanical parameters were assessed in mesenteric arteries by pressure myography. SOLF, UOLF, and HF diet reduced contractile responses to phenylephrine and induced endothelial dysfunction in the thoracic aorta. A significant increase in the β-index, and thus in arterial stiffness, was also detected in mesenteric arteries from the three HF groups, due to enhanced deposition of collagen in the vascular wall. SOLF also induced hypotrophic inward remodeling. In conclusion, these data demonstrate a deleterious effect of HF feeding on obesity-related vascular alterations that is exacerbated by SFA.