Improved induction of anti-melanoma T cells by adenovirus-5/3 fiber modification to target human DCs

To mount a strong anti-tumor immune response, non T cell inflamed (cold) tumors may require combination treatment encompassing vaccine strategies preceding checkpoint inhibition. In vivo targeted delivery of tumor-associated antigens (TAA) to dendritic cells (DCs), relying on the natural functions of primary DCs in situ, represents an attractive vaccination strategy. In this study we made use of a full-length MART-1 expressing C/B-chimeric adenoviral vector, consisting of the Ad5 capsid and the Ad3 knob (Ad5/3), which we previously showed to selectively transduce DCs in human skin and lymph nodes. Our data demonstrate that chimeric Ad5/3 vectors encoding TAA, and able to target human DCs in situ, can be used to efficiently induce expansion of functional tumor-specific CD8⁺ effector T cells, either from a naïve T cell pool or from previously primed T cells residing in the melanoma-draining sentinel lymph nodes (SLN). These data support the use of Ad3-knob containing viruses as vaccine vehicles for in vivo delivery. "Off-the-shelf" DC-targeted Ad vaccines encoding TAA could clearly benefit future immunotherapeutic approaches

The ecosystem carbon sink implications of mountain forest expansion into abandoned grazing land: The role of subsoil and climatic factors

Woody encroachment is a widespread phenomenon resulting from the abandonment of mountain agricultural and pastoral practices during the last century. As a result, forests have expanded, increasing biomass and necromass carbon (C) pools. However, the impact on soil organic carbon (SOC) is less clear. The main aim of this study was to investigate the effect of woody encroachment on SOC stocks and ecosystem C pools in six chronosequences located along the Italian peninsula, three in the Alps and three in the Apennines. Five stages along the chronosequences were identified in each site. Considering the topsoil (0 30 cm), subsoil (30 cm-bedrock) and whole soil profile, the temporal trend in SOC stocks was similar in all sites, with an initial increment and subsequent decrement in the intermediate phase. However, the final phase of the woody encroachment differed significantly between the Alps (mainly conifers) and the Apennines (broadleaf forests) sites, with a much more pronounced increment in the latter case. Compared to the previous pastures, after mature forest (>62 years old) establishment, SOC stocks increased by: 2.1(mean) ± 18.1(sd) and 50.1 ± 25.2 Mg C·ha -1 in the topsoil, 7.3 ± 17.4 and 93.2 ± 29.7 Mg C·ha -1 in the subsoil, and 9.4 ± 24.4 and 143.3 ± 51.0 Mg C·ha -1 in the whole soil profile in Alps and Apennines, respectively. Changes in SOC stocks increased with mean annual air temperature and average minimum winter temperature, and were negatively correlated with the sum of summer precipitation. At the same time, all other C pools (biomass and necromass) increased by 179.1 ± 51.3 and 304.2 ± 67.6 Mg C·ha -1 in the Alps and the Apennines sites, respectively. This study highlights the importance of considering both the subsoil, since deep soil layers contributed 38% to the observed variations in carbon stocks after land use change, and the possible repercussions for the carbon balance of large areas where forests are expanding, especially under pressing global warming scenarios. © 2019 Elsevier B.V.The project of this work is part of the research activities of the PhD in science, technology and biotechnology for sustainability. The first author received a fully founded scholarship partially by the University of Tuscia (Viterbo - Italy) and partially by the University of Molise . Tommaso Chiti participated in the project by conducting his work with the funding obtained through the LIFE MediNet project (grant number LIFE15 PRE IT/732295 ). Jorge Curiel Yuste was financed in part by the Basque Government through the BERC 2018-2021 (grant code) program and by Spanish Ministry of Economy and Competitiveness (MINECO) through BC3 María de Maeztu excellence accreditation MDM-2017-0714. I.C (grant code)

Peculiarities of the function of cardiomyocytes in patients with ischemic heart disease associated with diabetes mellitus type 2

The functional activity of myocardium in patients with type 2 diabetes mellitus(T2DM) and coronary heart disease (CAD) was studied. The study included patients with CAD with T2DM as representatives of the main group, the comparison group consisted of patients with univariant course of ischemic heart disease without violation of carbohydrate metabolism. Contractile activity of the myocardium was evaluated by the inotroic reaction of isolated trabeculae of patients according to the Protocol tests "Post-rest" and "Ekstrasistoliei test". As a result, it was found that rhythm-inotropic myocardial response in patients with comorbid pathology persists to a greater extent than in the one-dimensional flow of CAD

Looking deeper into the soil : biophysical controls and seasonal lags of soil CO2 production and efflux

Author Posting. © Ecological Society of America, 2010. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Ecological Applications 20 (2010): 1569–1582, doi:10.1890/09-0693.1.We seek to understand how biophysical factors such as soil temperature (Ts), soil moisture (θ), and gross primary production (GPP) influence CO2 fluxes across terrestrial ecosystems. Recent advancements in automated measurements and remote-sensing approaches have provided time series in which lags and relationships among variables can be explored. The purpose of this study is to present new applications of continuous measurements of soil CO2 efflux (F0) and soil CO2 concentrations measurements. Here we explore how variation in Ts, θ, and GPP (derived from NASA's moderate-resolution imaging spectroradiometer [MODIS]) influence F0 and soil CO2 production (Ps). We focused on seasonal variation and used continuous measurements at a daily timescale across four vegetation types at 13 study sites to quantify: (1) differences in seasonal lags between soil CO2 fluxes and Ts, θ, and GPP and (2) interactions and relationships between CO2 fluxes with Ts, θ, and GPP. Mean annual Ts did not explain annual F0 and Ps among vegetation types, but GPP explained 73% and 30% of the variation, respectively. We found evidence that lags between soil CO2 fluxes and Ts or GPP provide insights into the role of plant phenology and information relevant about possible timing of controls of autotrophic and heterotrophic processes. The influences of biophysical factors that regulate daily F0 and Ps are different among vegetation types, but GPP is a dominant variable for explaining soil CO2 fluxes. The emergence of long-term automated soil CO2 flux measurement networks provides a unique opportunity for extended investigations into F0 and Ps processes in the near future.Data collection was possible thanks to NASA, the NSF Center for Embedded Networked Sensing (CCR-0120778), DOE (DE-FG02-03ER63638), CONACyT, UCMEXUS, NSF (EF-0410408), NSF-LTER, KAKENHI (12878089 and 13480150), the Academy of Finland (213093), the Austrian Science Fund (FWF, P18756-B16), the Kearney Foundation, the Canadian Foundation for Climate and Atmospheric Sciences (CFCAS), and the Natural Science and Engineering Research Council of Canada (NSERC). R. Vargas was supported by grant DEB-0639235 during the preparation of this manuscript

High resolution AMI Large Array imaging of spinning dust sources: spatially correlated 8 micron emission and evidence of a stellar wind in L675

We present 25 arcsecond resolution radio images of five Lynds Dark Nebulae (L675, L944, L1103, L1111 & L1246) at 16 GHz made with the Arcminute Microkelvin Imager (AMI) Large Array. These objects were previously observed with the AMI Small Array to have an excess of emission at microwave frequencies relative to lower frequency radio data. In L675 we find a flat spectrum compact radio counterpart to the 850 micron emission seen with SCUBA and suggest that it is cm-wave emission from a previously unknown deeply embedded young protostar. In the case of L1246 the cm-wave emission is spatially correlated with 8 micron emission seen with Spitzer. Since the MIR emission is present only in Spitzer band 4 we suggest that it arises from a population of PAH molecules, which also give rise to the cm-wave emission through spinning dust emission.Comment: accepted MNRA

Realization of a fractional period adiabatic superlattice

We propose and realize a deeply sub-wavelength optical lattice for ultracold neutral atoms using $N$ resonantly Raman-coupled internal degrees of freedom. Although counter-propagating lasers with wavelength $\lambda$ provided two-photon Raman coupling, the resultant lattice-period was $\lambda/2N$, an $N$-fold reduction as compared to the conventional $\lambda/2$ lattice period. We experimentally demonstrated this lattice built from the three $F=1$ Zeeman states of a $^{87}{\rm Rb}$ Bose-Einstein condensate, and generated a lattice with a $\lambda/6= 132\ {\rm nm}$ period from $\lambda=790 \ {\rm nm}$ lasers. Lastly, we show that adding an additional RF coupling field converts this lattice into a superlattice with $N$ wells uniformly spaced within the original $\lambda/2$ unit cell.Comment: 5 pagesl 4 figure