Center and surround excitation in the receptive fields of frog retinal ganglion cells

We have reexamined the receptive fields of frog retinal ganglion cells focussing on their surround properties. Carefully excluding artifacts due to stimulation of the (Gaussian) RF center, we found that spiking responses can be elicited by step stimulation of any receptor type in the surrounds of all the classes 1–4 Maturana et al. (1960) (J. gen. Physiol. 43, 129–175). The surround responses are antagonized by the responsive center and suppressed by the inhibitory surround, but are seen because of their slower dynamics. The responsive surround differs spectrally from the center: in the latter, cones and green rods compete, in the former, their signals sum

Waterfalls as sources of small charged aerosol particles

In this study, we measured the mobility distributions of cluster and intermediate ions with an ion spectrometer near a waterfall. We observed that the concentration of negative 1.5–10 nm ions was one-hundred fold higher than a reference point 100 m away from the waterfall. Also, the concentration of positive intermediate ions was found to be higher than that at the reference point by a factor of ten. This difference was observed only at the smallest sizes; above 10 nm the difference was insignificant

Winter to spring transition and diurnal variation of VOCs in Finland at an urban background site and a rural site

Peer reviewe

Cognitive Effects of White Matter Pathology in Normal and Pathological Aging

We examined whether cerebrovascular white matter pathology is related to cognition as measured by the compound score of CERAD neuropsychological battery in cognitively normal older adults, patients with mild cognitive impairment, and patients with Alzheimer's disease (total n = 149), controlling for age and education. Trend-level effects of white matter pathology on cognition were only observed in patients with Alzheimer's disease (p = 0.062, eta(2) = 0.052), patients with severe frontal white matter pathology performed notably worse than those with milder pathology. This indicates that frontal cerebrovascular pathology may have an additive negative effect on cognition in Alzheimer's disease

A look at aerosol formation using data mining techniques

International audienceAtmospheric aerosol particle formation is frequently observed throughout the atmosphere, but despite various attempts of explanation, the processes behind it remain unclear. In this study data mining techniques were used to find the key parameters needed for atmospheric aerosol particle formation to occur. A dataset of 8 years of 80 variables collected at the boreal forest station (SMEAR II) in Southern Finland was used, incorporating variables such as radiation, humidity, SO2, ozone and present aerosol surface area. Data analysis were done using clustering and classification methods. The aim of this approach was to gain new parameters independent of any subjective interpretation. This resulted in two key parameters, relative humidity and preexisting aerosol particle surface (condensation sink), capable in explaining 88% of the nucleation events. The inclusion of any further parameters did not improve the results notably. Using these two variables it was possible to derive a nucleation probability function. Interestingly, the two most important variables are related to mechanisms that prevent the nucleation from starting and particles from growing, while parameters related to initiation of particle formation seemed to be less important. Nucleation occurs only with low relative humidity and condensation sink values. One possible explanation for the effect of high water content is that it prevents biogenic hydrocarbon ozonolysis reactions from producing sufficient amounts of low volatility compounds, which might be able to nucleate. Unfortunately the most important biogenic hydrocarbon compound emissions were not available for this study. Another effect of water vapour may be due to its linkage to cloudiness which may prevent the formation of nucleating and/or condensing vapours. A high number of preexisting particles will act as a sink for condensable vapours that otherwise would have been able to form sufficient supersaturation and initiate the nucleation process

Holistic evaluation of the environmental impacts of shipping in the sensitive region of Ria de Aveiro

© 2024 The Authors. Published by Elsevier B.V. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Shipping activity can be a substantial source of pollution and impact on the environment, including air, water and ecosystems, as well as adverse health and climatic effects. Due to the distribution of maritime transport activity routes in the EU, a large portion of the population is exposed to shipping pollution throughout Europe. The ongoing European project EMERGE aims to investigate and quantify these impacts over Europe, and in more detail, in specific case studies regions. The Aveiro lagoon region in Portugal is one of these case studies. This region is a Natura 2000 area, and also includes a medium-sized port. Both air quality and water modelling tools were applied to assess the impact of the emissions and discharges from shipping (to air and water) in the region in 2018. Additionally, ecotoxicological impacts were determined by bioassays to evaluate the impact of scrubber-water discharges on the most sensitive stages of marine invertebrates, and on the post-exposure feeding inhibition of crustacean and bivalve species. The results show that there was a substantial increase in atmospheric pollutant concentrations due to emissions attributed to shipping, which was most relevant for NOx and SO2 (up to a 30 % shipping contribution). There was no significant degradation of the water quality, mainly as the ships operating in this area did not have scrubber equipment. The ecotoxicological tests were performed with three samples of scrubber water, including one artificial sample and two samples collected on-board ships. If scrubber water would have been discharged in this area, the results indicated that the majority of the tested species would be exposed to lowest observed effect concentration (LOEC) for the different scrubber-water samples, as well as to substantial concentrations of metals, PAHs, and alkylated PAHs.Peer reviewe

New insights into nocturnal nucleation

Formation of new aerosol particles by nucleation and growth is a significant source of aerosols in the atmosphere. New particle formation events usually take place during daytime, but in some locations they have been observed also at night. In the present study we have combined chamber experiments, quantum chemical calculations and aerosol dynamics models to study nocturnal new particle formation. All our approaches demonstrate, in a consistent manner, that the oxidation products of monoterpenes play an important role in nocturnal nucleation events. By varying the conditions in our chamber experiments, we were able to reproduce the very different types of nocturnal events observed earlier in the atmosphere. The exact strength, duration and shape of the events appears to be sensitive to the type and concentration of reacting monoterpenes, as well as the extent to which the monoterpenes are exposed to ozone and potentially other atmospheric oxidants

A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines

Besides the isolation and identification of major histocompatibility complex I-restricted peptides from the surface of cancer cells, one of the challenges is eliciting an effective antitumor CD8+ T-cell-mediated response as part of therapeutic cancer vaccine. Therefore, the establishment of a solid pipeline for the downstream selection of clinically relevant peptides and the subsequent creation of therapeutic cancer vaccines are of utmost importance. Indeed, the use of peptides for eliciting specific antitumor adaptive immunity is hindered by two main limitations: the efficient selection of the most optimal candidate peptides and the use of a highly immunogenic platform to combine with the peptides to induce effective tumor-specific adaptive immune responses. Here, we describe for the first time a streamlined pipeline for the generation of personalized cancer vaccines starting from the isolation and selection of the most immunogenic peptide candidates expressed on the tumor cells and ending in the generation of efficient therapeutic oncolytic cancer vaccines. This immunopeptidomics-based pipeline was carefully validated in a murine colon tumor model CT26. Specifically, we used state-of-the-art immunoprecipitation and mass spectrometric methodologies to isolate > 8000 peptide targets from the CT26 tumor cell line. The selection of the target candidates was then based on two separate approaches: RNAseq analysis and HEX software. The latter is a tool previously developed by Jacopo, 2020, able to identify tumor antigens similar to pathogen antigens in order to exploit molecular mimicry and tumor pathogen cross-reactive T cells in cancer vaccine development. The generated list of candidates (26 in total) was further tested in a functional characterization assay using interferon-gamma enzyme-linked immunospot (ELISpot), reducing the number of candidates to six. These peptides were then tested in our previously described oncolytic cancer vaccine platform PeptiCRAd, a vaccine platform that combines an immunogenic oncolytic adenovirus (OAd) coated with tumor antigen peptides. In our work, PeptiCRAd was successfully used for the treatment of mice bearing CT26, controlling the primary malignant lesion and most importantly a secondary, nontreated, cancer lesion. These results confirmed the feasibility of applying the described pipeline for the selection of peptide candidates and generation of therapeutic oncolytic cancer vaccine, filling a gap in the field of cancer immunotherapy, and paving the way to translate our pipeline into human therapeutic approach.Peer reviewe

Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency

Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient's clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny.Peer reviewe

The impact of the duration of the palliative care period on cancer patients with regard to the use of hospital services and the place of death: a retrospective cohort study

Background: In order to avoid unnecessary use of hospital services at the end-of-life, palliative care should be initiated early enough in order to have sufficient time to initiate and carry out good quality advance care planning (ACP). This single center study assesses the impact of the PC decision and its timing on the use of hospital services at EOL and the place of death. Methods: A randomly chosen cohort of 992 cancer patients treated in a tertiary hospital between Jan 2013 -Dec 2014, who were deceased by the end of 2014, were selected from the total number of 2737 identified from the hospital database. The PC decision (the decision to terminate life-prolonging anticancer treatments and focus on symptom centered palliative care) and use of PC unit services were studied in relation to emergency department (ED) visits, hospital inpatient days and place of death. Results: A PC decision was defined for 82% of the patients and 37% visited a PC unit. The earlier the PC decision was made, the more often patients had an appointment at the PC unit (> 180 days prior to death 72% and Conclusions: The PC decision to initiate a palliative goal for the treatment had a distinct impact on the use of hospital services at the EOL. Contact with a PC unit further increased the likelihood of EOL care at primary care.</div