Controlled Synthesis of Up-Conversion NaYF4:Yb,Tm Nanoparticles for Drug Release under Near IR-Light Therapy

Up-Conversion materials have received great attention in drug delivery applications in recent years. A specifically emerging field includes the development of strategies focusing on photon processes that promote the development of novel platforms for the efficient transport and the controlled release of drug molecules in the harsh microenvironment. Here, modified reaction time, thermal treatment, and pH conditions were controlled in the synthesis of NaYF(4):Yb,Tm up-converted (UC) material to improve its photoluminescence properties. The best blue-emission performance was achieved for the UC3 sample prepared through 24 h-synthesis without thermal treatment at a pH of 5, which promotes the presence of the β-phase and smaller particle size. NaYF(4):Yb,Tm has resulted in a highly efficient blue emitter material for light-driven drug release under near-IR wavelength. Thus, NaYF(4):Yb,Tm up-converted material promotes the N-O bond cleavage of the oxime ester of Ciprofloxacin (prodrug) as a highly efficient photosensitized drug delivery process. HPLC chromatography and transient absorption spectroscopy measurements were performed to evaluate the drug release conversion rate. UC3 has resulted in a very stable and easily recovered material that can be used in several reaction cycles. This straightforward methodology can be extended to other drugs containing photoactive chromophores and is present as an alternative for drug release systems

RIAM-VASP module relays integrin complement receptors in outside-in signaling driving particle engulfment

The phagocytic integrins and complement receptors M 2/CR3 and X 2/CR4 are classically associated with the phagocytosis of iC3b-opsonized particles. The activation of this receptor is dependent on signals derived from other receptors (inside-out signaling) with the crucial involvement of the Rap1-RIAM-Talin-1 pathway. Here, we analyze the implication of RIAM and its binding partner VASP in the signaling events occurring downstream of 2 integrins (outside-in) during complement-mediated phagocytosis. To this end, we used HL-60 promyelocytic cell lines deficient in RIAM or VASP or overexpressing EGFP-tagged VASP to determine VASP dynamics at phagocytic cups. Our results indicate that RIAM-deficient HL-60 cells presented impaired particle internalization and altered integrin downstream signaling during complement-dependent phagocytosis. Similarly, VASP deficiency completely blocked phagocytosis, while VASP overexpression increased the random movement of phagocytic particles at the cell surface, with reduced internalization. Moreover, the recruitment of VASP to particle contact sites, amount of pSer157-VASP and formation of actin-rich phagocytic cups were dependent on RIAM expression. Our results suggested that RIAM worked as a relay for integrin complement receptors in outside-in signaling, coordinating integrin activation and cytoskeletal rearrangements via its interaction with VASPThis work has been supported by Ministerio Español de Economía y Competitividad (MINECO) grants: SAF2016-77096-R (ELD and CC), BIO2014:54164-R (PAR), BIO2017-86500-R (MY-M), EI/MICIU EXPLORA BIO2017-91272-EXP & FEDER (PI17/02303) (S.R.-P). AT-G is supported by a predoctoral fellowship from MINECO, JLS-T is supported by a predoctoral fellowship from Universidad Complutense de Madrid, RT-R is supported by a postdoctoral fellowship from Asociación Española Contra el Cáncer (AECC

Scaling laws in granular flow and pedestrian flow

We use particle-based simulations to examine the flow of particles through an exit. Simulations involve both gravity-driven particles (representing granular material) and velocity-driven particles (mimicking pedestrian dynamics). Contact forces between particles include elastic, viscous, and frictional forces; and simulations use bunker geometry. Power laws are observed in the relation between flow rate and exit width. Simulations of granular flow showed that the power law has little dependence on the coefficient of friction. Polydisperse granular systems produced higher flow rates than those produced by monodisperse ones. We extend the particle model to include the main features of pedestrian dynamics: thoracic shape, shoulder rotation, and desired velocity oriented towards the exit. Higher desired velocity resulted in higher flow rate. Granular simulations always give higher flow rate than pedestrian simulations, despite the values of aspect ratio of the particles. In terms of force distribution, pedestrians and granulates share similar properties with the non-democratic distribution of forces that poses high risks of injuries in a bottleneck situation

Identification of Altered Evoked and Non-Evoked Responses in a Heterologous Mouse Model of Endometriosis-Associated Pain

The aim of this study was to develop and refine a heterologous mouse model of endometriosis-associated pain in which non-evoked responses, more relevant to the patient experience, were evaluated. Immunodeficient female mice (N = 24) were each implanted with four endometriotic human lesions (N = 12) or control tissue fat (N = 12) on the abdominal wall using tissue glue. Evoked pain responses were measured biweekly using von Frey filaments. Non-evoked responses were recorded weekly for 8 weeks using a home cage analysis (HCA). Endpoints were distance traveled, social proximity, time spent in the center vs. outer areas of the cage, drinking, and climbing. Significant differences between groups for von Frey response, climbing, and drinking were detected on days 14, 21, and 35 post implanting surgery, respectively, and sustained for the duration of the experiment. In conclusion, a heterologous mouse model of endometriosis-associated evoked a non-evoked pain was developed to improve the relevance of preclinical models to patient experience as a platform for drug testing

Analysis of the discrepancies between the vertical reference frames of Argentina and Brazil

The vertical reference frames for Argentina and Brazil present discrepancies due to their different datums and realizations. Thus, since 2008, we have started a series of activities with the aim of unifying the Argentine and Brazilian national vertical networks (NVNs). To achieve this goal, we have connected the two NVNs at three border points by using the geodetic levelling approach. Additionally, the gravity field approach was also applied, based on a suitable representation of the geoid by considering the Earth GravitationalModel (EGM2008) in its full resolution. In this regard, 1266 co-located Global Positioning System (GPS) and levelling benchmarks regularly distributed over Argentina (612) and Brazil (654) were considered. The geodetic levelling approach shows an offset value of 54 cm, which implies that the Argentine vertical reference frame is above that of the Brazilian vertical reference frame. However, the result of the gravimetric approach shows an offset of 57 cm, which implies a difference of approximately 3 cm between both methods. Hence, since Brazil and Argentina represent a significant part of South America, the solution to the datum problem between both countries could point towards a common vertical reference frame for the Atlantic side.Facultad de Ciencias Agrarias y Forestale

Mining Virulence Genes Using Metagenomics

When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity. In free-living bacteria (for instance marine bacteria compared against the ocean metagenome) certain genomic regions are totally absent in recruitment plots, representing therefore genes unique to individual bacterial isolates. We show that these Metagenomic Islands (MIs) are also visible in bacteria living in human hosts when their genomes are compared to sequences from the human microbiome, despite the compartmentalized structure of human-related environments such as the gut. From an applied point of view, MIs of human pathogens (e.g. those identified in enterohaemorragic Escherichia coli against the gut metagenome or in pathogenic Neisseria meningitidis against the oral metagenome) include virulence genes that appear to be absent in related strains or species present in the microbiome of healthy individuals. We propose that this strategy (i.e. recruitment analysis of pathogenic bacteria against the metagenome of healthy subjects) can be used to detect pathogenicity regions in species where the genes involved in virulence are poorly characterized. Using this approach, we detect well-known pathogenicity islands and identify new potential virulence genes in several human pathogens

Impact of Neuroprotection on Incidence of Alzheimer's Disease

Converging evidence suggests that high levels of education and intellectual activity increase the cognitive reserve and reduce the risk of dementia. However, little is known about the impact that different neuroprotective strategies may have on the incidence of Alzheimer's disease. Using a simple mathematical regression model, it is shown here that age-specific counts of basic cognitive units (surrogate of neurons or synapses) in the normal population can be estimated from Alzheimer's incidence rates. Hence, the model can be used to test the effect of neuroprotection on Alzheimer's incidence. It was found that the number of basic cognitive units decreases with age, but levels off in older people. There were no gender differences after correcting for survival. The model shows that even modest neuroprotective effects on basic cognitive units can lead to dramatic reductions in the number of Alzheimer's cases. Most remarkably, a 5% increase in the cognitive reserve would prevent one third of Alzheimer's cases. These results suggest that public health policies aimed at increasing the cognitive reserve in the general population (e.g., implementing higher levels of education) are likely the most effective strategy for preventing Alzheimer's disease

Resonances from lattice QCD

The spectrum of hadron is mainly composed as shortly-lived states (resonance) that decay onto two or more hadrons. These resonances play an important role in a variety of phenomenologically significant processes. In this talk, I give an overview on the present status of a rigorous program for studying of resonances and their properties using lattice QCD. I explain the formalism needed for extracting resonant amplitudes from the finite-volume spectra. From these one can extract the masses and widths of resonances. I present some recent examples that illustrate the power of these ideas. I then explain similar formalism that allows for the determination of resonant electroweak amplitudes from finite-volume matrix elements. I use the recent calculation of the πγ* → ππ amplitude as an example illustrating the power of this formalism. From such amplitudes one can determine transition form factors of resonances. I close by reviewing on-going efforts to generalize these ideas to increasingly complex reactions and I then give a outlook of the field

Globally invariant metabolism but density-diversity mismatch in springtails.

Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy