The hippocampal formation is considered essential for spatial navigation. In particular, subicular projections have been suggested to carry spatial information from the hippocampus to the ventral ...striatum. However, possible cross-structural communication between these two brain regions in memory formation has thus far been unknown. By selectively silencing the subiculum-ventral striatum pathway we found that its activity after learning is crucial for spatial memory consolidation and learning-induced plasticity. These results provide new insight into the neural circuits underlying memory consolidation and establish a critical role for off-line cross-regional communication between hippocampus and ventral striatum to promote the storage of complex information.
Background
Autologous blood transfusion is one of the illicit strategies, banned by the World Anti-Doping Agency, to increase the levels of hemoglobin, with a consequent improvement in the delivery ...of oxygen to tissues. At present, this practice is detectable exclusively by the individual, longitudinal monitoring of hematological biomarkers, as in the hematological module of the Athlete Biological Passport; but this indirect approach may suffer from different confounding factors. We are presenting a multi-parametric, analytical strategy to detect autologous blood transfusions by targeting the modification of the red blood cells during storage. We focused on the assessment of “storage lesions”, targeting (i) membrane proteins: Glycophorin-A and Band 3 complex, (ii) biomarkers of oxidative stress: Peroxiredoxin-2, (iii) biomarkers of senescence: CD47 and Phosphatidylserine, (iv) erythrocytes microparticles.
Results
All of the above markers were monitored, by immunological and flow cytofluorimetric methods, on samples of stored whole blood collected at different time intervals, and on fresh blood samples, collected for official doping control tests, mixed “ex vivo” to simulate an autotransfusion. Although anonymized before the delivery to the laboratory, it was possible to mix samples belonging to the same subject based on the “athlete biological passport” code. Our results showed that the irreversible alteration of RBCs morphology, the loss of membrane integrity, the occurrence of hemolysis phenomena, and, more in general, the “aging” of the erythrocytes during storage are closely related to: (i) the reduced concentration, on the erythrocyte membrane, of Band 3 protein (decrease of 19% and of 39% after 20 and 40 days of storage respectively) and of glycophorin A (− 47% and − 63% respectively); (ii) the externalization of phosphatidyl serine (with a five-fold increase after 20 days and a further 2× increase after 40 days); (iii) the reduced concentration of CD47; and (iv) increased levels of erythrocyte microparticles.
Conclusions
The most promising method to detect the presence of transfused blood in whole blood samples can be based on a multi-parametric strategy, considering jointly both protein expression on RBCs membranes and micro-vesiculation phenomena.
Key Points
Potential biomarkers of “blood storage” were specifically considered in this study to detect autologous blood transfusions in sport doping.
The irreversible alteration of RBCs morphology, the loss of membrane integrity, the occurrence of hemolysis phenomena, and, more in general, the “aging” of the erythrocytes during storage are closely related to: (i) the reduction, on the erythrocyte membrane, of Band 3 protein and of glycophorin A; (ii) the externalization of phosphatidyl serine; (iii) the reduced concentration of CD47; and (iv) the increased levels of erythrocyte microparticles.
Freshly collected samples showed differences from stored or mixed ones in terms of both protein expression on the RBCs membranes and micro-vesiculation phenomena.
Research projects in structural biology increasingly rely on combinations of heterogeneous sources of information, e.g. evolutionary information from multiple sequence alignments, experimental ...evidence in the form of density maps and proximity constraints from proteomics experiments. The OpenStructure software framework, which allows the seamless integration of information of different origin, has previously been introduced. The software consists of C++ libraries which are fully accessible from the Python programming language. Additionally, the framework provides a sophisticated graphics module that interactively displays molecular structures and density maps in three dimensions. In this work, the latest developments in the OpenStructure framework are outlined. The extensive capabilities of the framework will be illustrated using short code examples that show how information from molecular‐structure coordinates can be combined with sequence data and/or density maps. The framework has been released under the LGPL version 3 license and is available for download from http://www.openstructure.org.
Radioguided surgery (RGS) is a medical practice which thanks to a radiopharmaceutical tracer and a probe allows the surgeon to identify tumor residuals up to a millimetric resolution in real-time. ...The employment of β− emitters, instead of γ or β+, reduces background from healthy tissues, administered activity to the patient, and medical exposure. In a previous work the possibility of using a CMOS Imager (Aptina MT9V011), initially designed for visible light imaging, to detect β− from 90Y or 90Sr sources has been established. Because of its possible application as counting probe in RGS, the performances of MT9V011 in clinical-like conditions were studied.11This work financed by Istituto Nazionale Fisica Nucleare, Italy, project CHIR2, and partially supported by Universitá degli Studi di Perugia, Italy , Fondo Ricerca di Base 2017, project SEISIPO.
Through horizontal scans on a collimated 90Sr source of different sizes (1, 3, 5, 7 mm), we have determined relationships between scan fit parameters and the source dimension, namely A quadratic correlation and a linear dependency of, respectively, signal integrated over scan interval, and maximum signal against source diameter, are determined. Horizontal scan measurements on a source, interposing collimators of different size, aim to determine relationships or correlations between scan fit parameters and source dimension. A quadratic correlation and a linear dependency of, respectively, signal integrated over scan interval, and maximum signal against source diameter are determined.
In order to get closer to clinical conditions, agar–agar phantoms containing 90Y with different dimensions and activities were prepared. A 90Y phantom is characterized by a central spot and a ring all around, for simulating both signal (tumor) and background (surrounding healthy tissue). The relationship found between scan maximum and 90Sr source diameter is then exploited to extract the concentration ratio between spot and external ring of the 90Y phantom. This observable, defined as the ratio between the tumor and the nearby healthy tissues uptake simulates the Tumor-to-Non-tumor Ratio (TNR). With the aim of evaluating the sensor’s ability to discriminate signal from background relying on the significance parameter, a further 90Y phantom, featuring a well-known and clinical-like activity will mimic the signal only condition. This result is used to extrapolate to different source sizes, after having estimated the background for various TNR. The obtained significance values suggest that the MT9V011 sensor is capable of distinguishing a signal from an estimated background, depending on the interplay among TNR, acquisition time and tumor diameter.
•A CMOS imager has been used as sensor for beta- emission from isotopes (90Y) of interest in Radioguided surgery.•Using a position scan a correlation between the source dimension and the shape of the response has been found.•The sensitivity of the sensor to tumor detection has been determined by studying the interplay among TNR, acquisition time and tumor diameter.
Hematopoietic stem cells (HSC) are multipotent progenitor cells, resident primarily in human bone marrow. Their main function is the continuous renewal of all hematopoietic cells. A small fraction of ...HSC is also circulating in peripheral blood (cHSC) where they can be possibly detected thanks to the application of the new very sensitive flow cytometry methodologies.
In recent times it has been debated whether the utilization of several different types of stem cells can be abused by athletes for doping purposes. Moreover, there is growing knowledge that the dynamic and turnover of circulating HSC may reflect changes affecting the physiologic processes at the erythropoietic level; also, cHSC and other circulating hematopoietic progenitors (cHP) resulted to give different responses in athletes engaged in endurance and maximal exercise sports. If it is true that the use of stem cells (mainly mesenchymal stem cells) to allow a rapid recover from an injury is not considered a doping practice, it is also true that the 2022 WADA list of prohibited substances and methods forbids “the use of normal or genetically modified cells” as well as “any form of intravascular manipulation of the blood or blood components by physical or chemical means”. In this context, HSC and hematopoietic erythroid progenitors may be a potential threat and the possibility of their abuse needs to be exploited in sport antidoping.
In view of the above, we have preliminarily assessed the possibility of detecting circulating hematopoietic stem cells by flow cytofluorimetry. In details, we applied two flow cytofluorimetric protocols for the accurate and precise counting of circulating HSC, also discussing the potential applicability in a potential antidoping scenario. We concluded that i) flow cytofluorimetry is a pratical and rapid platform for the identification and the counting of cHSC and other erythroid progenitors in peripheral human whole blood, ii) the correlation between CD34+ circulating progenitors and standard haematological parameters may be an effective new tool to be exploited as in direct markers of blood doping and, iii) accurate baseline levels of HSC and erythroid progenitors need to be determined in order to identify abuses of HSC and/or conventional blood doping.
The CMS experiment at the Large Hadron Collider will have a large Silicon Strip Tracker. The status of the project is here reviewed. The detector layout is presented, and the main components are ...described. The construction of such a large scale detector requires an adequate organization in terms of production and quality assurance. Finally the tests performed on the system are presented.
The Fermi surface (FS) of URu2Si2 in the paramagnetic phase has been reinvestigated via the measurement of the two-dimensional angular correlation of the positron annihilation radiation. Unlike ...previous measurements our experiment provides evidence that density-functional theory gives a fair qualitative description of the FS, showing a large contribution from the 5f electrons, although the Fermi volume of electron and hole pockets determined experimentally is smaller than the theoretical description. Furthermore, we propose a method to investigate the nature of the hidden order responsible for the 17.5 K transition.
Measurement of the angular correlation of the electron-positron annihilation radiation complemented with ab initio calculations can provide decisive information about the character of f electrons in ...actinide compounds. Our studies of the antiferromagnet UGa3 in the paramagnetic phase produce substantial evidence that an unconstrained f-electron itinerant description applies.
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