Brain tissue properties differentiate between motor and limbic basal ganglia circuits

Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcom

GIADA performance during Rosetta mission scientific operations at comet 67P

The Grain Impact Analyser and Dust Accumulator (GIADA) instrument onboard Rosetta studied the dust environment of comet 67P/Churyumov–Gerasimenko from 3.7 au inbound, through perihelion, to 3.8 au outbound, measuring the dust flow and the dynamic properties of individual particles. GIADA is composed of three subsystems: 1) Grain Detection System (GDS); 2) Impact Sensor (IS); and 3) Micro-Balances System (MBS). Monitoring the subsystems’ performance during operations is an important element for the correct calibration of scientific measurements. In this paper, we analyse the GIADA inflight calibration data obtained by internal calibration devices for the three subsystems during the period from 1 August 2014 to 31 October 2015. The calibration data testify a nominal behaviour of the instrument during these fifteen months of mission; the only exception is a minor loss of sensitivity for one of the two GDS receivers, attributed to dust contamination

The dust-to-ices ratio in comets and Kuiper belt objects

Comet 67P/Churyumov-Gerasimenko (67P hereinafter) is characterized by a dust transfer from the southern hemi-nucleus to the night-side northern dust deposits, which constrains the dust-to-ices mass ratio inside the nucleus to values a factor of 2 larger than that provided by the lost mass of gas and non-volatiles. This applies to all comets because the gas density in all night comae cannot prevent the dust fallback. Taking into account Grain Impact Analyser and Dust Accumulator (GIADA) data collected during the entire Rosetta mission, we update the average dust bulk density to ρD=785 +520/−115 $\rho {}{}_{\rm D} = 785_{-115}^{+520}$ kg m$^-3$ that, coupled to the 67P nucleus bulk density, confirms an average dust-to-ices mass ratio δ = 7.5 inside 67P. The improved dust densities are consistent with a mixture of (20 ± 8) per cent of ices, (4 ± 1) per cent of Fe sulphides, (22 ± 2) per cent of silicates and (54 ± 5) per cent of hydrocarbons, on average volume abundances. These values correspond to solar chemical abundances, as suggested by the elemental C/Fe ratio observed in 67P. The ice content in 67P matches that inferred in Kuiper belt objects, (20 ± 12) per cent on average volume abundance and suggests a water content in all trans-Neptunian objects lower than in CI chondrites. The 67P icy pebbles and the dust collected by GIADA have a microporosity of (49 ± 5) and (59 ± 8) per cent, respectively

Mucosal immune response after the booster dose of the BNT162b2 COVID-19 vaccine

Background: To date, only a few studies reported data regarding the development of mucosal immune response after the BNT162b2-booster vaccination. Methods: Samples of both serum and saliva of 50 healthcare workers were collected at the day of the booster dose (T3) and after two weeks (T4). Anti-S1-protein IgG and IgA antibody titres and the neutralizing antibodies against the Wuhan wild-type Receptor-Binding Domain in both serum and saliva were measured by quantitative and competitive ELISA, respectively. Data were compared with those recorded after the primary vaccination cycle (T2). Neutralizing antibodies against the variants of concern were measured in those individuals with anti-Wuhan neutralizing antibodies in their saliva. Findings: After eight months from the second dose, IgG decreased in both serum (T2GMC: 23,838.5 ng/ml; T3GMC: 1473.8 ng/ml) and saliva (T2GMC: 12.9 ng/ml; T3GMC: 0.3 ng/ml). Consistently, serum IgA decreased (T2GMC: 48.6 ng/ml; T3GMC: 6.4 ng/ml); however, salivary IgA showed a different behaviour and increased (T2GMC: 0.06 ng/ml; T3GMC: 0.41 ng/ml), indicating a delayed activation of mucosal immunity. The booster elicited higher titres of both IgG and IgA when compared with the primary cycle, in both serum (IgG T4GMC: 98,493.9 ng/ml; IgA T4GMC: 187.5 ng/ml) and saliva (IgG T4GMC: 21.9 ng/ml; IgA T4GMC: 0.65 ng/ml). Moreover, the booster re-established the neutralizing activity in the serum of all individuals, not only against the Wuhan wild-type antigen (N = 50; INH: 91.6%) but also against the variants (Delta INH: 91.3%; Delta Plus INH: 89.8%; Omicron BA.1 INH: 85.1%). By contrast, the salivary neutralizing activity was high against the Wuhan antigen in 72% of individuals (N = 36, INH: 62.2%), but decreased against the variants, especially against the Omicron BA.1 variant (Delta N = 27, INH: 43.1%; Delta Plus N = 24, INH: 35.2%; Omicron BA.1 N = 4; INH: 4.7%). This was suggestive for a different behaviour of systemic immunity observed in serum with respect to mucosal immunity described in saliva (Wald chi-square test, 3 df of interaction between variants and sample type = 308.2, p < 0.0001). Interpretation: The BNT162b2-booster vaccination elicits a strong systemic immune response but fails in activating an effective mucosal immunity against the Omicron BA.1 variant. Funding: This work was funded by the Department of Medicine and Surgery, University of Insubria, and supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020), Italy

Comet 67P/Churyumov-Gerasimenko preserved the pebbles that formed planetesimals

Solar System formation models predict that the building-blocks of planetesimals were mm- to cm-sized pebbles, aggregates of ices and non-volatile materials, consistent with the compact particles ejected by comet 67P/Churyumov-Gerasimenko (67P hereafter) and detected by GIADA (Grain Impact Analyzer and Dust Accumulator) on-board the Rosetta spacecraft. Planetesimals were formed by the gentle gravitational accretion of pebbles, so that they have an internal macroporosity of 40%. We measure the average dust bulk density ${\rho}D = 795 _{-65}^{+840} kg m^{-3}$ that, coupled to the 67P nucleus bulk density, provides the average dust-to-ices mass ratio δ = 8.5. We find that the measured densities of the 67P pebbles are consistent with a mixture of (15 ± 6)% of ices, (5 ± 2)% of Fe-sulfides, (28 ± 5)% of silicates, and (52 ± 12)% of hydrocarbons, in average volume abundances. This composition matches both the solar and CI-chondritic chemical abundances, thus showing that GIADA has sampled the typical non-volatile composition of the pebbles that formed all planetesimals. The GIADA data do not constrain the abundance of amorphous silicates vs. crystalline Mg,Fe- olivines and pyroxenes. We find that the pebbles have a microporosity of (52 ± 8)% (internal volume filling factor φP = 0.48±0.08), implying an average porosity for the 67P nucleus of (71 ± 8)%, lower than previously estimated

Optimal MHC-II-restricted tumor antigen presentation to CD4+ T helper cells: the key issue for development of anti-tumor vaccines

Present immunoprevention and immunotherapeutic approaches against cancer suffer from the limitation of being not “sterilizing” procedures, as very poor protection against the tumor is obtained. Thus newly conceived anti-tumor vaccination strategies are urgently needed. In this review we will focus on ways to provide optimal MHC class II-restricted tumor antigen presentation to CD4+ T helper cells as a crucial parameter to get optimal and protective adaptive immune response against tumor. Through the description of successful preventive or therapeutic experimental approaches to vaccinate the host against the tumor we will show that optimal activation of MHC class II-restricted tumor specific CD4+ T helper cells can be achieved in various ways. Interestingly, the success in tumor eradication and/or growth arrest generated by classical therapies such as radiotherapy and chemotherapy in some instances can be re-interpreted on the basis of an adaptive immune response induced by providing suitable access of tumor-associated antigens to MHC class II molecules. Therefore, focussing on strategies to generate better and suitable MHC class II–restricted activation of tumor specific CD4+ T helper cells may have an important impact on fighting and defeating cancer