The pharmacological perturbation of brain zinc impairs BDNF-related signaling and the cognitive performances of young mice.

Zinc (Zn2+) is a pleiotropic modulator of the neuronal and brain activity. The disruption of intraneuronal Zn2+ levels triggers neurotoxic processes and affects neuronal functioning. In this study, we investigated how the pharmacological modulation of brain Zn2+ affects synaptic plasticity and cognition in wild-type mice. To manipulate brain Zn2+ levels, we employed the Zn2+ (and copper) chelator 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol, CQ). CQ was administered for two weeks to 2.5-month-old (m.o.) mice, and effects studied on BDNF-related signaling, metalloproteinase activity as well as learning and memory performances. CQ treatment was found to negatively affect short- and long-term memory performances. The CQ-driven perturbation of brain Zn2+ was found to reduce levels of BDNF, synaptic plasticity-related proteins and dendritic spine density in vivo. Our study highlights the importance of choosing "when", "where", and "how much" in the modulation of brain Zn2+ levels. Our findings confirm the importance of targeting Zn2+ as a therapeutic approach against neurodegenerative conditions but, at the same time, underscore the potential drawbacks of reducing brain Zn2+ availability upon the early stages of development

Epidemiology of hypertension in Yemen: effects of urbanization and geographical area

Although globalization can contribute to increased blood pressure by spreading unhealthy behaviors, it also provides powerful means to tackle hypertension. The dissemination of information about and advice on cardiovascular prevention and facilitated contact with health services are valuable resources. To investigate the effects of urbanization, geographical area, and air temperature on hypertension burden and kidney damage, a survey was performed in 2008 with a door-to-door approach among urban and rural adult dwellers of three geographic areas (capital, inland, coast) of Yemen. Subjects (n=10 242) received two visits several days apart to confirm the diagnosis of hypertension. Proteinuria (dipstick test ⩾+1) was used as a marker of kidney damage. Prevalence rates were weighted to represent the Yemen population aged 15–69 years in 2008. Rates of hypertension and proteinuria progressively increased from the capital (6.4% 95% confidence level (CI) 5.8–7.0 and 5.1% 4.4–5.9, respectively), to inland areas (7.9% 7.0–8.7 and 6.1% 5.1–7.1), to the coastal area (10.1% 8.9–11.4 and 8.9% 7.3–10.4). When compared with urban dwellers, rural dwellers had similar hypertension prevalence (adjusted odds ratios (ORs) 1.03; 95% CI 0.91–1.17) but higher proteinuria rates (adjusted ORs 1.55; 1.31–1.85). Overall, home temperature was associated with a lower hypertension rate (adjusted OR 0.98; 0.96–0.99). This large population study reveals that the highest burden of hypertension and kidney damage is detectable in remote areas of the country

Inhibition of de novo ceramide biosynthesis affects aging phenotype in an in vitro model of neuronal senescence.

Although aging is considered to be an unavoidable event, recent experimental evidence suggests that the process can be counteracted. Intracellular calcium (Ca2+i) dyshomeostasis, mitochondrial dysfunction, oxidative stress, and lipid dysregulation are critical factors that contribute to senescence-related processes. Ceramides, a pleiotropic class of sphingolipids, are important mediators of cellular senescence, but their role in neuronal aging is still largely unexplored. In this study, we investigated the effects of L-cycloserine (L-CS), an inhibitor of thede novoceramide biosynthesis, on the aging phenotype of cortical neurons cultured for 22 days, a setting employed as anin vitromodel of senescence. Our findings indicate that, compared to control cultures, 'aged' neurons display dysregulation of [Ca2+]ilevels, mitochondrial dysfunction, increased generation of reactive oxygen species (ROS), altered synaptic activity as well as the activation of neuronal death-related molecules. Treatment with L-CS positively affected the senescent phenotype, a result associated with recovery of neuronal [Ca2+]isignaling and reduction of mitochondrial dysfunction and ROS generation. The results suggest that thede novoceramide biosynthesis represents a critical intermediate in the molecular and functional cascade leading to neuronal senescence and identify ceramide biosynthesis inhibitors as promising pharmacological tools to decrease age-related neuronal dysfunctions

Planetary space weather: scientific aspects and future perspectives

International audienceIn this paper, we review the scientific aspects of planetary space weather at different regions of our Solar System, performing a comparative planetology analysis that includes a direct reference to the circum-terrestrial case. Through an interdisciplinary analysis of existing results based both on observational data and theoretical models, we review the nature of the interactions between the environment of a Solar System body other than the Earth and the impinging plasma/radiation, and we offer some considerations related to the planning of future space observations. We highlight the importance of such comparative studies for data interpretations in the context of future space missions (e.g. ESA JUICE; ESA/JAXA BEPI COLOMBO). Moreover, we discuss how the study of planetary space weather can provide feedback for better understanding the traditional circum-terrestrial space weather. Finally, a strategy for future global investigations related to this thematic is proposed

Investigation of the possible effects of comet Encke's meteoroid stream on the Ca exosphere of Mercury

The MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) observations of the seasonal variability of Mercury's Ca exosphere are consistent with the general idea that the Ca atoms originate from the bombardment of the surface by particles from comet 2P/Encke. The generating mechanism is believed to be a combination of different processes including the release of atomic and molecular surface particles and the photodissociation of exospheric molecules. Considering different generation and loss mechanisms, we perform simulations with a 3-D Monte Carlo model based on the exosphere generation model by Mura et al. (2009). We present for the first time the 3-D spatial distribution of the CaO and Ca exospheres generated through the process of micrometeoroid impact vaporization, and we show that the morphology of the latter is consistent with the available MESSENGER/Mercury Atmospheric and Surface Composition Spectrometer observations. The results presented in this paper can be useful in the exosphere observations planning for BepiColombo, the upcoming European Space Agency-Japanese Aerospace Exploration Agency mission to Mercury

Short-term observations of double-peaked Na emission from Mercury's exosphere

We report the analysis of short-term ground-based observations of the exospheric Na emission (D1 and D2 lines) from Mercury, which was characterized by two high-latitude peaks confined near the magnetospheric cusp footprints. During a series of scheduled observations from the Télescope Héliographique pour l'Etude du Magnétisme et des Instabilités Solaires (THEMIS) telescope, achieved by scanning the whole planet, we implemented a series of extra measurements by recording the Na emission from a narrow north-south strip only, centered above the two emission peaks. Our aim was to inspect the existence of short-term variations, which were never analyzed before from ground-based observations, and their possible correlation with interplanetary magnetic field variations. Though Mercury possesses a miniature magnetosphere, characterized by fast reconnection events that develop on a timescale of few minutes, ground-based observations show that the exospheric Na emission pattern can be globally stable for a prolonged period (some days) and also exhibits fluctuations in the time range of tens of minutes

Analytical model of Europa's O2 exosphere

The origin of the exosphere of Europa is its water ice surface. The existing exosphere models, assuming either a collisionless environment (simple Monte Carlo techniques) or a kinetic approach (Direct Monte Carlo Method) both predict that the major constituent of the exosphere is molecular oxygen. Specifically, O2 is generated at the surface through radiolysis and chemical interactions of the water dissociation products. The non-escaping O2 molecules circulate around the moon impacting the surface several times, due to their long lifetime and due to their non- sticking, suffering thermalization to the surface temperature after each impact. In fact, the HST observations of the O emission lines proved the presence of an asymmetric atomic Oxygen distribution, related to a thin asymmetric molecular Oxygen atmosphere. The existing Monte Carlo models are not easily applicable as input of simulations devoted to the study of the plasma interactions with the moon. On the other hand, the simple exponential density profiles cannot well depict the higher temperature/higher altitudes component originating by radiolysis. It would thus be important to have a suitable and user-friendly model able to describe the major exospheric characteristics to use as a tool. This study presents an analytical 3D model that is able to describe the molecular Oxygen exosphere by reproducing the two-component profiles and the asymmetries due to diverse configurations among Europa, Jupiter and the Sun. This model is obtained by a non-linear fit procedure of the EGEON Monte Carlo model (Plainaki et al. 2013) to a Chamberlain density profile. Different parameters of the model are able to describe various exosphere properties thus allowing a detailed investigation of the exospheric characteristics. As an example a discussion on the exospheric temperatures in different configurations and space regions is given

The H2O and O2 exospheres of Ganymede: The result of a complex interaction between the jovian magnetospheric ions and the icy moon

The H2O and O2 exospheres of Jupiter's moon Ganymede are simulated through the application of a 3D Monte Carlo modeling technique that takes into consideration the combined effect on the exosphere generation of the main surface release processes (i.e. sputtering, sublimation and radiolysis) and the surface precipitation of the energetic ions of Jupiter's magnetosphere. In order to model the magnetospheric ion precipitation to Ganymede's surface, we used as an input the electric and magnetic fields from the global MHD model of Ganymede's magnetosphere (Jia, X., Walker, R.J., Kivelson, M.G., Khurana, K.K., Linker, J.A. [2009]. J. Geophys. Res. 114, A09209). The exospheric model described in this paper is based on EGEON, a single-particle Monte Carlo model already applied for a Galilean satellite (Plainaki, C., Milillo, A., Mura, A., Orsini, S., Cassidy, T. [2010]. Icarus 210, 385-395; Plainaki, C., Milillo, A., Mura, A., Orsini, S., Massetti, S., Cassidy, T. [2012]. Icarus 218 (2), 956-966; Plainaki, C., Milillo, A., Mura, A., Orsini, S., Saur [2013]. Planet. Space Sci. 88, 42-52); nevertheless, significant modifications have been implemented in the current work in order to include the effect on the exosphere generation of the ion precipitation geometry determined strongly by Ganymede's intrinsic magnetic field (Kivelson, M.G. et al. [1996]. Nature 384, 537-541). The current simulation refers to a specific configuration between Jupiter, Ganymede and the Sun in which the Galilean moon is located close to the center of Jupiter's Plasma Sheet (JPS) with its leading hemisphere illuminated. Our results are summarized as follows: (a) at small altitudes above the moon's subsolar point the main contribution to the neutral environment comes from sublimated H2O; (b) plasma precipitation occurs in a region related to the open-closed magnetic field lines boundary and its extent depends on the assumption used to mimic the plasma mirroring in Jupiter's magnetosphere; (c) the spatial distribution of the directly sputtered-H2O molecules exhibits a close correspondence with the plasma precipitation region and extends at high altitudes, being, therefore, well differentiated from the sublimated water; (d) the O2 exosphere comprises two different regions: the first one is an homogeneous, relatively dense, close to the surface thermal-O2 region (extending to some 100s of km above the surface) whereas the second one is less homogeneous and consists of more energetic O2 molecules sputtered directly from the surface after water-dissociation by ions has taken place; the spatial distribution of the energetic surface-released O2 molecules depends both on the impacting plasma properties and the moon's surface temperature distribution (that determine the actual efficiency of the radiolysis process)

Exospheric Na distributions along the Mercury orbit with the THEMIS telescope

Abstract The Na exosphere of Mercury is characterized by the variability of the emission lines intensity and of its distribution in time scales from less than one hour to seasonal variations. While the faster variations, accounting for about 10–20% of fluctuations are probably linked to the planetary response to solar wind and Interplanetary Magnetic Field variability, the seasonal variations (up to about 80%) should be explained by complex mechanisms involving different surface release processes, loss, source and migrations of the exospheric Na atoms. Eventually, a Na annual cycle can be identified. In the past, ground-based observations and equatorial density from MESSENGER data have been analyzed. In this study, for a more extensive investigation of the exospheric Na features, we have studied the local time and latitudinal distributions of the exospheric Na column density as a function of the True Anomaly Angle (TAA) of Mercury by means of the extended dataset of images, collected from 2009 to 2013, by the THEMIS solar telescope. Our results show that the THEMIS images, in agreement with previous results, registered a strong general increase in sodium abundance at aphelion and a dawn ward emission predominance with respect to dusk ward and subsolar region between 90° and 150° TAA. This behavior can be explained by desorption of a sodium surface reservoir consisting of sodium that is pushed anti-sunward and condenses preferentially in the coldest regions. Our analyses show s a predominance of subsolar line-of-sight column density along the rest of Mercury's orbit. An unexpected relationship between Northward or Southward peak emission and both TAA and local time is also shown by our analysis. This result seems to contradict previous results obtained from different data sets and it is not easily explained, thus it requires further investigations

A Machine Learning-Based Holistic Approach to Predict the Clinical Course of Patients within the Alzheimer’s Disease Spectrum

Background: Alzheimer’s disease (AD) is a neurodegenerative condition driven by multifactorial etiology. Mild cognitive impairment (MCI) is a transitional condition between healthy aging and dementia. No reliable biomarkers are available to predict the conversion from MCI to AD. Objective: To evaluate the use of machine learning (ML) on a wealth of data offered by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Alzheimer’s Disease Metabolomics Consortium (ADMC) database in the prediction of the MCI to AD conversion. Methods: We implemented an ML-based Random Forest (RF) algorithm to predict conversion from MCI to AD. Data related to the study population (587 MCI subjects) were analyzed by RF as separate or combined features and assessed for classification power. Four classes of variables were considered: neuropsychological test scores, AD-related cerebrospinal fluid (CSF) biomarkers, peripheral biomarkers, and structural magnetic resonance imaging (MRI) variables. Results: The ML-based algorithm exhibited 86% accuracy in predicting the AD conversion of MCI subjects. When assessing the features that helped the most, neuropsychological test scores, MRI data, and CSF biomarkers were the most relevant in the MCI to AD prediction. Peripheral parameters were effective when employed in association with neuropsychological test scores. Age and sex differences modulated the prediction accuracy. AD conversion was more effectively predicted in females and younger subjects. Conclusion: Our findings support the notion that AD-related neurodegenerative processes result from the concerted activity of multiple pathological mechanisms and factors that act inside and outside the brain and are dynamically affected by age and sex