Density and reproductive characteristics of female brown bears in the Cantabrian Mountains, NW Spain

Here we present annual nearest-neighbour distances (as a proxy of density) between females with cubs-of-the-year (hereafter FCOY) and reproductive characteristics of brown bears Ursus arctos in the Cantabrian Mountains (NW Spain), from 1989 to 2017. FCOY nearest-neighbour distances and reproduction parameters of 19 focal females followed over several consecutive years (from 2004 to 2017) were obtained from bears inhabiting the western sector of the Cantabrian Mountains, where most of the bear population resides. In contrast, general reproductive characteristics were studied in the whole Cantabrian Mountains (western and eastern sectors together) on a sample of 362 litter sizes and 695 cubs. Mean nearest-neighbour distance between FCOY was 2559 ± 1222 m (range = 1305–4757 m). Mean litter size was significantly larger in the west (1.8 ± 0.2 cubs) than in the east (1.3 ± 0.6 cubs). Mean litter size for the whole of the Cantabrian Mountains was 1.6 ± 0.3 cubs. Litter sizes of one, two and three cubs represented 33.4, 56.1 and 10.5% of observed family groups, respectively. Interannual variations in litter size were not significant for both the western and the eastern areas. Mean cub mortality was 0.2 ± 0.5 cubs and did not vary among years. Cub mortality per litter size was 3.9% for one cub, 69.2% for two cubs and 26.9% for three cubs. Mean reproductive rate of the 19 focal females was 1.5 ± 0.6 cubs (n = 58 litters). Litter size of focal FCOY did not differ from the litter size obtained from systematic observations in the whole Cantabrian Mountains. During this period, cub mortality occurred in 24.1% of the 58 litters. Females usually bred every second year (average litter interval = 2.2 years). The estimated reproductive rate for the bear population was 0.7 young born/year/reproductive adult female

DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy

Natural killer (NK) cells are lymphocytes of the innate immune response characterized by their role in the destruction of tumor cells. Activation of NK cells depend on a fine balance between activating and inhibitory signals mediated by different receptors. In recent years, a family of paired receptors that interact with ligands of the Nectin/Nectin-like (Necl) family has attracted great interest. Two of these ligands, Necl-5 (usually termed CD155 or PVR) and Nectin-2 (CD112), frequently expressed on different types of tumor cells, are recognized by a group of receptors expressed on T and NK cells that exert opposite functions after interacting with their ligands. These receptors include DNAM-1 (CD226), TIGIT, TACTILE (CD96) and the recently described PVRIG. Whereas activation through DNAM-1 after recognition of CD155 or CD112 enhances NK cell-mediated cytotoxicity against a wide range of tumor cells, TIGIT recognition of these ligands exerts an inhibitory effect on NK cells by diminishing IFN-γ production, as well as NK cell-mediated cytotoxicity. PVRIG has also been identified as an inhibitory receptor that recognizes CD112 but not CD155. However, little is known about the role of TACTILE as modulator of immune responses in humans. TACTILE control of tumor growth and metastases has been reported in murine models, and it has been suggested that it negatively regulates the anti-tumor functions mediated by DNAM-1. In NK cells from patients with solid cancer and leukemia, it has been observed a decreased expression of DNAM-1 that may shift the balance in favor to the inhibitory receptors TIGIT or PVRIG, further contributing to the diminished NK cell-mediated cytotoxic capacity observed in these patients. Analysis of DNAM-1, TIGIT, TACTILE and PVRIG on human NK cells from solid cancer or leukemia patients will clarify the role of these receptors in cancer surveillance. Overall, it can be speculated that in cancer patients the TIGIT/PVRIG pathways are upregulated and represent novel targets for checkpoint blockade immunotherapy

Surface-charge-induced orientation of interfacial water suppresses heterogeneous ice nucleation on α-alumina (0001)

Surface charge is one of the surface properties of atmospheric aerosols, which has been linked to heterogeneous ice nucleation and hence cloud formation, microphysics, and optical properties. Despite the importance of surface charge for ice nucleation, many questions remain on the molecular-level mechanisms at work. Here, we combine droplet-freezing assay studies with vibrational sum frequency generation (SFG) spectroscopy to correlate interfacial water structure to surface nucleation strength. We study immersion freezing of aqueous solutions of various pHs on the atmospherically relevant aluminum oxide α-Al2O3 (0001) surface using an isolated droplet on the surface. The high-pH solutions freeze at temperatures higher than that of the low-pH solution, while the neutral pH has the highest freezing temperature. On the molecular level, the SFG spectrum of the interfacial water changes substantially upon freezing. At all pHs, crystallization leads to a reduction of intensity of the 3400 cm−1 water resonance, while the 3200 cm−1 intensity drops for low pH but increases for neutral and high pHs. We find that charge-induced surface templating suppresses nucleation, irrespective of the sign of the surface charge. Heterogeneous nucleation is most efficient for the nominally neutral surface

Correlating Antimicrobial activity and Structure in Montmorillonite modified with Hexadecyltrimethylammonium and Silver

The relationship between antimicrobial properties and structure of montmorillonite (MMT) containing hexadecyltrimethylammonium bromide (HDTMA-Br) and silver (Ag) was determined. HDTMA was adsorbed at the clay interlayer by a cation exchange, through the positive head of the ammonium group. At higher surfactant loadings (100 and 200% cation exchange capacity (CEC); MH1 and MH2 samples, respectively) the prevalence of weak adsorption (Van der Waals forces) was observed; whereas below the clay CEC (50%, MH0.5) strong interactions predominated (cation exchange). These different interactions impacted on antimicrobial activity, increasing bactericidal capacity when the surfactant was more available to diffuse. For organo-montmorillonites (OMMT) and all samples with Ag, zeta potential pointed out electrical charge changes on the outer surface, respect to MMT. XPS analyses showed peaks attributed to clusters formation, silver oxidation, and Ag0 in MMTAg and MH0.5-Ag. The Ag0 peak was also present in MH1-Ag and MH2-Ag, the later showing an extra peak associated with AgBr. HDMTA+ and Ag adsorbed on the MMT acted synergistically against Staphylococcus aureus. This effect was less noticeable for Escherichia coli and the result was attributed to both, E. coli outer envelope which might lower the efficacy of HDMTA+ adsorbed on the MMT, and decreasing silver proportions when the surfactant loading increased. MH1-Ag presented the best bactericidal properties, showing synergistic effects against S. aureus, while maintaining activity against E. coli compared to MMT-Ag. Understanding MMT-HDMTA-Ag efficacy contributes to the design of new antimicrobial materials for potential applications in health careFil: Fernández Solarte, Alejandra María. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; Argentina. Corporacion Universitaria Minuto de Dios.; ColombiaFil: Blanco Massani, Mariana Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Industrial; ArgentinaFil: Molina, Vanesa Magali. Instituto Nacional de Tecnología Industrial; ArgentinaFil: Benítez Guerrero, Mónica. Universidad de Malaga. Facultad de Ciencias; EspañaFil: Torres Sánchez, Rosa M.. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; Argentin

Role of plasma membrane lipid composition on cellular homeostasis: learning from cell line models expressing fatty acid desaturases

Experimental evidence has suggested that plasma membrane (PM)-associated signaling and hence cell metabolism and viability depend on lipid composition and organization. The aim of the present work is to develop a cell model to study the endogenous polyunsaturated fatty acids (PUFAs) effect on PM properties and analyze its influence on cholesterol (Chol) homeostasis. We have previously shown that by using a cell line over-expressing stearoyl-CoA-desaturase, membrane composition and organization coordinate cellular pathways involved in Chol efflux and cell viability by different mechanisms. Now, we expanded our studies to a cell model over-expressing both Δ5 and Δ6 desaturases, which resulted in a permanently higher PUFA content in PM. Furthermore, this cell line showed increased PM fluidity, Chol storage, and mitochondrial activity. In addition, human apolipoprotein A-I-mediated Chol removal was less efficient in these cells than in the corresponding control. Taken together, our results suggested that the cell functionality is preserved by regulating PM organization and Chol exportation and homeostasis.Instituto de Investigaciones Bioquímicas de La PlataFacultad de Ciencias Médica

Escuela y comunidad. La experiencia colombiana con los Proyectos de Servicio Social Estudiantil

One of the most difficult problems that the school is currently facing is that it generates encapsulated knowledge and learning processes that are disarticulated from the characteristics of the context which defines students. Against this background, it is proposed that learning- service can become an alternative that manages to articulate the knowledge of the school with the community in order to generate authentic learning processes. Based on these premises, this article presents a practical study on Student Social Service Projects (SSSP), as an alternative to overcome the dualistic school-community vision. The SSSP is a state requirement that every student from public or private education in Colombia must meet in the upper grades and which, from the theory, is recognized as a scenario of articulation between the school, the community, and the individual. However, the findings show a series of difficulties that have limited its educational scope and reveal a historically fragmented and lacking national educational system, from which the school needs to be rethought and re-signified to strengthen the learning and training processes of students.Uno de los grandes problemas a los se que enfrenta actualmente la escuela, es que se generan conocimientos y procesos de aprendizaje encapsulados y desarticulados de las características del contexto que definen a sus estudiantes. Frente a este panorama, se plantea que el aprendizaje por servicio puede erigirse como una alternativa que logra articular los saberes de la escuela con la comunidad en miras de generar procesos de aprendizaje auténtico. A partir de estas premisas, este artículo presenta un estudio práctico sobre los Proyectos de Servicio Social Estudiantil (PSSE), como alternativa para superar la visión dualista escuela-comunidad. Los PSSE son un requisito estatal que todo estudiante de educación pública o privada de Colombia debe cumplir en los grados superiores y que, desde la teoría, se reconoce como un escenario de articulación entre la escuela, la comunidad y el individuo. Sin embargo, los hallazgos evidencian una serie de dificultades que han limitado su alcance formativo y dejan entrever un sistema educativo nacional históricamente fragmentado y lleno de carencias, desde el que la escuela necesita ser repensada y resignificada para fortalecer los procesos de aprendizaje y formación de los estudiantes.Universidad Pablo de Olavid

Expression of placental glycans and its role in regulating peripheral blood NK cells during preeclampsia: a perspective

Preeclampsia is a pregnancy-related multisystem disorder characterized by altered trophoblast invasion, oxidative stress, exacerbation of systemic inflammatory response, and endothelial damage. The pathogenesis includes hypertension and mild-to-severe microangiopathy in the kidney, liver, placenta, and brain. The main mechanisms involved in its pathogenesis have been proposed to limit trophoblast invasion and increase the release of extracellular vesicles from the syncytiotrophoblast into the maternal circulation, exacerbating the systemic inflammatory response. The placenta expresses glycans as part of its development and maternal immune tolerance during gestation. The expression profile of glycans at the maternal–fetal interface may play a fundamental role in physiological pregnancy changes and disorders such as preeclampsia. It is unclear whether glycans and their lectin-like receptors are involved in the mechanisms of maternal–fetal recognition by immune cells during pregnancy homeostasis. The expression profile of glycans appears to be altered in hypertensive disorders of pregnancy, which could lead to alterations in the placental microenvironment and vascular endothelium in pregnancy conditions such as preeclampsia. Glycans with immunomodulatory properties at the maternal–fetal interface are altered in early-onset severe preeclampsia, implying that innate immune system components, such as NK cells, exacerbate the systemic inflammatory response observed in preeclampsia. In this article, we discuss the evidence for the role of glycans in gestational physiology and the perspective of glycobiology on the pathophysiology of hypertensive disorders in gestation

Mössbauer thermal scan study of a spin crossover system

Programmable Velocity equipment was used to perform a Mössbauer Thermal Scans to allow a quasi-continuous temperature study of the magnetic transition between the low-spin and a high-spin configurations in [Fe(Htrz)2(trz)](BF4) system. The material was studied both in bulk as in nanoparticles sample forms.Facultad de Ciencias ExactasInstituto de Física La PlataInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia

Background: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. Methods: We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. Results: NK cells, CD56− T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56− T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1−TIGIT+TACTILE+ NK cells and DNAM-1− TIGIT+TACTILE+ CD56− T cells were associated with a better survival of AML patients. Conclusions: The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade

Non-conservation of folding rates in the thioredoxin family reveals degradation of ancestral unassisted-folding

Evolution involves not only adaptation, but also the degradation of superfluous features. Many examples of degradation at the morphological level are known (vestigial organs, for instance). However, the impact of degradation on molecular evolution has been rarely addressed. Thioredoxins serve as general oxidoreductases in all cells. Here, we report extensive mutational analyses on the folding of modern and resurrected ancestral bacterial thioredoxins. Contrary to claims from recent literature, in vitro folding rates in the thioredoxin family are not evolutionarily conserved, but span at least a ∼100-fold range. Furthermore, modern thioredoxin folding is often substantially slower than ancestral thioredoxin folding. Unassisted folding, as probed in vitro, thus emerges as an ancestral vestigial feature that underwent degradation, plausibly upon the evolutionary emergence of efficient cellular folding assistance. More generally, our results provide evidence that degradation of ancestral features shapes, not only morphological evolution, but also the evolution of individual proteins.This research was supported by FEDER Funds, grant BIO2015-66426-R from the Spanish Ministry of Economy and Competitiveness ( J.M.S.-R.), grant RGP0041/2017 from the Human Frontier Science Program ( J.M.S.-R. and E.A.G.) and National Institutes of Health 1R01AR069137 (E.A.G.), Department of Defence MURI W911NF-16-1-0372 (E.A.G.)