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Breaking an impasse in finding mechanism-based therapies of neuropsychiatric disorders requires a strategic shift towards alleviating individual symptoms. Here we present a symptom and circuit-specific approach to rescue deficits of reward learning in Fmr1 knockout mice, a model of Fragile X syndrome (FXS), the most common monogenetic cause of inherited mental disability and autism. We use high-throughput, ecologically-relevant automated tests of cognition and social behavior to assess effectiveness of the circuit-targeted injections of designer nanoparticles, loaded with TIMP metalloproteinase inhibitor 1 protein (TIMP-1). Further, to investigate the impact of our therapeutic strategy on neuronal plasticity we perform long-term potentiation recordings and high-resolution electron microscopy. We show that central amygdala-targeted delivery of TIMP-1 designer nanoparticles reverses impaired cognition in Fmr1 knockouts, while having no impact on deficits of social behavior, hence corroborating symptom-specificity of the proposed approach. Moreover, we elucidate the neural correlates of the highly specific behavioral rescue by showing that the applied therapeutic intervention restores functional synaptic plasticity and ultrastructure of neurons in the central amygdala. Thus, we present a targeted, symptom-specific and mechanism-based strategy to remedy cognitive deficits in Fragile X syndrome.

To evaluate individual variations in broccoli VOLTA F1 plants, the bioactive components of 15 florets that were cultivated in identical agricultural and climatic conditions were analyzed. Glucosinolates were analyzed by HPLC; total phenolic compounds, ascorbic and dehydroascorbic acids (vitamin C) and the DPPH[round bullet, filled] and OH[round bullet, filled] radical-scavenging activities of samples were also determined. Florets were characterized by particularly high glucoraphanin content, 17.95 μmol/g dry weight on average, which comprised about 50% of total glucosinolates. High individual variation was observed for several bioactive compounds, as well as for DPPH[round bullet, filled] and OH[round bullet, filled] radical-scavenging activity. Coefficients of variability (CVs) were high, and except for one case, exceeded 10%. Among glucosinolates, the highest CVs were noted for progoitrin (34.22%), 4-hydroxyglucobrassicin (27.32%) and neoglucobrassicin (24.44%). High CVs were also observed for vitamin C (29.11%), including dehydroascorbic acid (26.72%), and for OH[round bullet, filled] (25.76%) and DPPH[round bullet, filled] (21.77%) radical-scavenging activities. Smaller variations were found for glucoraphanin (CV = 14.84%) and polyphenols (CV = 14.95%).

Cardiovascular disease (CVD) is a major cause of morbidity and mortality throughout the world. The LIPIDOGRAM2015 study was performed to estimate the prevalence of risk factors for atherosclerotic diseases as well as cardiovascular and related disorders in the primary care setting in Poland. The LIPIDOGEN2015 sub-study was designed to include a random cohort of patients in order to analyse parameters related to lipid metabolism, oxidative stress, inflammatory responses, autoimmune disorders, and gene variants that confer susceptibility to cardiometabolic and atherosclerotic diseases. The recruitment was carried out by 438 primary care physicians in Poland. The expected number of patients recruited for the LIPIDOGRAM2015 study was 13,000-14,000 with 13-15% (1700-2000) also participating in the LIPIDOGEN2015 sub-study. Each patient had to complete a questionnaire concerning medical and family history, concomitant diseases, and pharmacotherapy. Anthropometric measurements were performed at the doctor's office. For the LIPIDOGEN2015 sub-study, saliva samples for DNA isolation and blood samples for measurement of glycated haemoglobin, oxidative stress parameters, autoantibody levels, and inflammatory cytokine profile and apolipoprotein profile were collected. Follow-up data will be obtained from the National Health Fund in Poland. The LIPIDOGRAM2015 and LIPIDOGEN2015 study cohort reflects the prevalence of cardiovascular risk factors and concomitant diseases, markers of oxidative stress, the presence of autoantibodies, inflammatory cytokine profile, and apolipoprotein profile, as well as genetic variants potentially conferring susceptibility to cardiometabolic and atherosclerotic diseases. This study presents the prevalence of different CV risk factors, with special emphasis on lipid disorders, and it assesses the relationship between inflammation, oxidative stress, and mutations in genes encoding proteins regulating lipid metabolism, as well as genes conferring susceptibility to cardiovascular, cardiometabolic, and related diseases.

Broccoli cooked in a convection steam oven at different temperatures and times was evaluated and compared with broccoli boiled in water. Broccoli was subjected to a sensory analysis, and its texture parameters were determined instrumentally. The effect of various thermal processing methods on pectic compounds was analysed. The application of different cooking methods led to significant variations in the analysed attributes. The majority of the observed differences were statistically significant (P < 0.05). Broccoli cooked in a convection steam oven at 125°C with 90% steam saturation for 8 min was characterised by the most desirable sensory attributes and scored 8.5 on a 10-cm unstructured line scale. The same samples had the greatest firmness and the highest protopectin content (72.9%). Broccoli boiled in water scored the lowest number of points, and it had the lowest protopectin content (51%).

Abstract Being a part of a social structure is key for survival and reproduction. Living with conspecifics boosts evolutionary fitness, by providing essential information about the environment. To examine how socially passed olfactory information about the reward affects behavior of individuals we used Eco-HAB, an automated system for tracing voluntary behavior of group-housed mice living under semi-naturalistic conditions. We show that presence of a scent of a rewarded individual has profound effects on social behavior of mice and their ability to find the reward in both familiar and novel environments. As a result, socially-conveyed information has different effects on individual mice. Further, we show that disrupting neuronal plasticity in the prelimbic cortex with nanoparticles gradually releasing TIMP metallopeptidase inhibitor 1, disrupts animals’ social behavior and results in decreased ability to adapt to environmental changes. The experimental paradigm we developed can be further used to study neuronal mechanisms of social learning. Competing Interest Statement The authors have declared no competing interest. Footnotes * https://drive.google.com/drive/folders/16RoSwbBwJ9XkN6mnLFLbCxvpee-AnaFn?usp=sharing

Recent observational efforts using imaging atmospheric Cherenkov telescopes (IACTs) have led to firm detections of very-high-energy (VHE) signals from bright gamma-ray bursts (GRBs), often at moderate redshifts. This work presents 15 years of H.E.S.S. GRB observations and examines their implications through population comparisons and selected modelling cases. GRBs are a key science target of the High Energy Stereoscopic System (H.E.S.S.). With a low-energy threshold (\\(\\lesssim\\)100 GeV) and rapid repointing capabilities, H.E.S.S. can begin follow-up observations within tens of seconds after a GRB trigger, covering the late prompt or early afterglow phases. We report GRB follow-up observations with H.E.S.S. from 2004 to 2019, which resulted in no significant VHE signals (aside from the detections of GRB~180720B and GRB~190829A). The resulting upper limits comprise the largest set available for GRBs at VHE. A subset of bursts with favourable conditions were selected for X-ray analysis and emission modelling. Population studies were performed to compare detected and non-detected GRBs. The results indicate that VHE-detected GRBs are not a distinct population, but tend to feature luminous X-ray emission and favourable redshift and observing conditions. This highlights the potential of next-generation IACTs such as the Cherenkov Telescope Array Observatory (CTAO), whose lower energy threshold will enhance the detection of fainter and more distant GRBs.

This research is aimed at determining the effect of different hydrothermal treatments of carrot on its organoleptic attributes and physical properties determining texture. A preliminary evaluation was performed on seven carrot varieties, of which the three were selected for study: Bangor, Fayette and Nektarina. In hydrothermally treated carrot, significant differences were observed in the intensity of sweet taste, cooked taste, uniformity and intensity of orange colour, and in physical properties including force and energy of extrusion and the extrudability index (p<0.05). These properties were found to be dependent on both carrot variety and the manner of hydrothermal treatment. Under the experimental conditions applied, hydrothermal treatment of the whole carrot root with steam was found to be optimal and the highest general sensation in terms of organoleptic attributes was reported for the Bangor variety.[PUBLICATION ABSTRACT]

Owing to their rapid cooling rate and hence loss-limited propagation distance, cosmic-ray electrons and positrons (CRe) at very high energies probe local cosmic-ray accelerators and provide constraints on exotic production mechanisms such as annihilation of dark matter particles. We present a high-statistics measurement of the spectrum of CRe candidate events from 0.3 to 40 TeV with the High Energy Stereoscopic System (H.E.S.S.), covering two orders of magnitude in energy and reaching a proton rejection power of better than \\(10^{4}\\). The measured spectrum is well described by a broken power law, with a break around 1 TeV, where the spectral index increases from \\(\\Gamma_1 = 3.25\\) \\(\\pm\\) 0.02 (stat) \\(\\pm\\) 0.2 (sys) to \\(\\Gamma_2 = 4.49\\) \\(\\pm\\) 0.04 (stat) \\(\\pm\\) 0.2 (sys). Apart from the break, the spectrum is featureless. The absence of distinct signatures at multi-TeV energies imposes constraints on the presence of nearby CRe accelerators and the local CRe propagation mechanisms.

HESS J1813\\(-\\)178 is a very-high-energy \\(\\gamma\\)-ray source spatially coincident with the young and energetic pulsar PSR J1813\\(-\\)1749 and thought to be associated with its pulsar wind nebula (PWN). Recently, evidence for extended high-energy emission in the vicinity of the pulsar has been revealed in the Fermi Large Area Telescope (LAT) data. This motivates revisiting the HESS J1813\\(-\\)178 region, taking advantage of improved analysis methods and an extended data set. Using data taken by the High Energy Stereoscopic System (H.E.S.S.) experiment and the Fermi-LAT, we aim to describe the \\(\\gamma\\)-ray emission in the region with a consistent model, to provide insights into its origin. We performed a likelihood-based analysis on 32 hours of H.E.S.S. data and 12 years of Fermi-LAT data and fit a spectro-morphological model to the combined datasets. These results allowed us to develop a physical model for the origin of the observed \\(\\gamma\\)-ray emission in the region. In addition to the compact very-high-energy \\(\\gamma\\)-ray emission centered on the pulsar, we find a significant yet previously undetected component along the Galactic plane. With Fermi-LAT data, we confirm extended high-energy emission consistent with the position and elongation of the extended emission observed with H.E.S.S. These results establish a consistent description of the emission in the region from GeV energies to several tens of TeV. This study suggests that HESS J1813\\(-\\)178 is associated with a \\(\\gamma\\)-ray PWN powered by PSR J1813\\(-\\)1749. A possible origin of the extended emission component is inverse Compton emission from electrons and positrons that have escaped the confines of the pulsar and form a halo around the PWN.