Maternal immune activation transgenerationally modulates maternal care and offspring depression-like behavior

AbstractGestational infection is increasingly being recognized for its involvement as causative mechanism in severe developmental brain abnormalities and its contribution to the pathogenesis of psychopathologies later in life. First observations in the widely accepted maternal immune activation (MIA) model based upon the systemic administration of the viral mimetic Polyinosinic:polycytidylic acid (poly(I:C)) have recently suggested a transmission of behavioral and transcriptional traits across generations. Although maternal care behavior (MCB) is known as essential mediator of the transgenerational effects of environmental challenges on offspring brain function and behavior, the possible propagation of alterations of MCB resulting from MIA to following generations has not yet been examined. Here we show that poly(I:C) stimulation at embryonic day 12.5 (E12.5) leads to aberrant MCB and that this effect is transmitted to the female F1 offspring. The transgenerational effects on MCB are paralleled by enhanced depression-like behavior in the second generation F2 offspring with contributions of both maternal and paternal heritages. Examination of offspring hippocampal expression of genes known as targets of MCB and relevant for ensuing non-genetic transmission of altered brain function and behavior revealed transgenerationally conserved and modified expressional patterns in the F1 and F2 generation.Collectively these data firstly demonstrate the transgenerational transmission of the impact of gestational immune activation on the reproductive care behavior of the mother. Behavioral and molecular characteristics of first and second generation offspring suggest transgenerationally imprinted consequences of gestational infection on psychopathological traits related to mood disorders which remain to be examined in future cross-fostering experiments

Evaluation of the diagnostic accuracy of two point-of-care tests for COVID-19 when used in symptomatic patients in community settings in the UK primary care COVID diagnostic accuracy platform trial (RAPTOR-C19)

Background and objective Point-of-care lateral flow device antigen testing has been used extensively to identify individuals with active SARS-CoV-2 infection in the community. This study aimed to evaluate the diagnostic accuracy of two point-of-care tests (POCTs) for SARS-CoV-2 in routine community care. Methods Adults and children with symptoms consistent with suspected current COVID-19 infection were prospectively recruited from 19 UK general practices and two COVID-19 testing centres between October 2020 and October 2021. Participants were tested by trained healthcare workers using at least one of two index POCTs (Roche-branded SD Biosensor Standard™ Q SARS-CoV-2 Rapid Antigen Test and/or BD Veritor™ System for Rapid Detection of SARS-CoV-2). The reference standard was laboratory triplex reverse transcription quantitative PCR (RT-PCR) using a combined nasal/oropharyngeal swab. Diagnostic accuracy parameters were estimated, with 95% confidence intervals (CIs), overall, in relation to RT-PCR cycle threshold and in pre-specified subgroups. Results Of 663 participants included in the primary analysis, 39.2% (260/663, 95% CI 35.5% to 43.0%) had a positive RT-PCR result. The SD Biosensor POCT had sensitivity 84.0% (178/212, 78.3% to 88.6%) and specificity 98.5% (328/333, 96.5% to 99.5%), and the BD Veritor POCT had sensitivity 76.5% (127/166, 69.3% to 82.7%) and specificity 98.8% (249/252, 96.6% to 99.8%) compared with RT-PCR. Sensitivity of both devices dropped substantially at cycle thresholds ≥30 and in participants more than 7 days after onset of symptoms. Conclusions Both POCTs assessed exceed the Medicines and Healthcare products Regulatory Agency target product profile’s minimum acceptable specificity of 95%. Confidence intervals for both tests include the minimum acceptable sensitivity of 80%. In symptomatic patients, negative results on these two POCTs do not preclude the possibility of infection. Tests should not be expected to reliably detect disease more than a week after symptom onset, when viral load may be reduced. Registration ISRCTN142269

Ganymede from 2D to 3D: A multidisciplinary approach in preparation for JUICE. Preliminary results

The research project: "Ganimede from 2D to 3D: A multidisciplinary approach in preparation for JUICE", was selected in 2019 in the framework of an "INAF Mainstream" call. This work aims to show the potential of a multidisciplinary data analysis approach in anticipation of the JUICE mission.We focus on three instruments carried onboard the ESA JUICE mission, where Italy's National Institute for Astrophysics (INAF) is involved: the optical camera (JANUS), sensitive to the 0.4-1.0 µm spectral region [1], the VIS-NIR imaging spectrometer (MAJIS), operating in the overall 0.5-5.54 µm spectral domain [2], and the radar sounder (RIME), operating at 9 MHz (33.3 m) [3]. This project is important to prepare combined analysis techniques and models that could be applied to a larger number of regions of interest that will be observed by JUICE in the 2030s, when data of the icy Galilean moons will be finally acquired. Here we show regions of interest on Ganymede that are most promising for a multi-sensor data analysis, first of all by combining optical images acquired by the Galileo/SSI framing camera and by the Galileo/NIMS imaging spectrometer with good spatial resolution. Unfortunately, topographic information is currently not available for most of the Ganymede's surface. However, we built a synthetic topographic dataset for the Nippur Sulcus region based on the existing high-resolution optical images, which could be representative of topographic models that will be obtained in the future by means of JUICE data. We process such a synthetic topographic dataset with a self-similar clustering method [e.g., 4] able to model how the fractures are distributed not only on the surface, but also inside the icy crust.In the near future, this synthetic topographic dataset will also be used to apply a code able to simulate radar echoes coming from the radio waves investigation of Ganymede's subsurface, which was successfully tested on Mars by means of the MARSIS radar data [5].Among other things, the study of specific regions of interest on Ganymede is key to drive the planning and prioritization of the observations to be carried out by multiple JUICE instruments, especially during the dedicated Ganymede orbit phase, which will be the final and salient phase of the entire mission. References [1] Della Corte, V., Noci, G., Turella, A., Paolinetti R., et al. (2019). Scientific objectives of JANUS Instrument onboard JUICE mission and key technical solutions for its Optical Head. Proceedings of the 2019 IEEE 5th International Workshop on Metrology for AeroSpace, Turin (Italy), 19-21 June 2019. Doi: 10.1109/MetroAeroSpace.2019.8869584. [2] Piccioni, G., Tommasi, L., Langevin, Y., Filacchione, G., et al. (2019). Scientific goals and technical challenges of the MAJIS imaging spectrometer for the JUICE mission. Proceedings of the 2019 IEEE 5th International Workshop on Metrology for AeroSpace, Turin (Italy), 19-21 June 2019. Doi: 10.1109/MetroAeroSpace.2019.8869566. [3] Bruzzone, L., Croci, R. (2019). Radar for Icy Moon Exploration (RIME). Proceedings of the 2019 IEEE 5th International Workshop on Metrology for AeroSpace, Turin (Italy), 19-21 June 2019. Doi: 10.1109/MetroAeroSpace.2019.8869624. [4] Lucchetti, A., Pozzobon, R., Mazzarini, F., Cremonese, G., Massironi, M. (2017). Brittle ice shell thickness of Enceladus from fracture distribution analysis. Icarus 297, 252-264. Doi: 10.1016/j.icarus.2017.07.009. [5] Orosei, R., Rossi, A. P., Cantini, F., Caprarelli, et al. (2017). Radar sounding of Lucus Planum, Mars, by MARSIS. Journal of Geophysical Research (Planets) 122 (7), 1405-1418. Doi: 10.1002/2016JE005232

Nippur Sulcus from 2D to 3D: A Multidisciplinary approach in preparation for JUICE

Summary. We focus on a portion of the Nippur Sulcus region on Ganymede, which is currently promising for a multisensor data analysis. We first combine data acquired by the Galileo/SSI framing camera and by the Galileo/NIMS imaging spectrometer. We then apply a self-similar clustering technique able to explain how the grooves visible on the surface are distributed inside the icy crust. Finally, we apply a simple model to obtain a synthetic topographic dataset based on the existing optical dataset, which is used to simulate radar echoes coming from the RIME instrument with the goal of evaluating the magnitude of clutter noise.Geological and compositional context. We first focus on optical images obtained by the Galileo/SSI framing camera on a portion of Nippur Sulcus bordering Galileo Regio to the east and Marius Regio to the west (167.4°E-193.5°E and 16.8°N-38.2°N) (Fig. 1). This region includes different terrain units, such as dark terrains, grooved terrains, and the palimpsest crater Epigeus [1].Fig. 1. Overview of the Nippur Sulcus region of inter-est used for our case study, from Ganymede's optical basemap (1 km/px). The violet contours highlight the regions for which high-resolution optical imagery is available, while the green contour highlights the region covered by hyperspectral, near-infrared (NIMS) data (see Fig. 2).The coverage obtained by the Galileo/NIMS imaging spectrometer [2] allows for the combination of geologic and compositional information, using specific spectral indices such as an IR slope, the 2-μm band depth, and a IR ratio, which can account for the distribution of contaminants, water ice, and grain size, respectively (Fig. 2).Fig. 2. NIMS Color composite map covering the Nip-pur Sulcus region at a spatial resolution of 6.7 km/px (R: IR slope 1.10-2.25 µm, G: 2-µm band depth, B: IR ratio between 3.6 µm and 1.82 µm). In the adopted color scheme, green marks high albedo, large (100s µm) regolith grains and stronger water ice band, while magenta is associated with dark terrain where the 2-µm water ice band is shallower and the grain size is smaller (10s of µm).Grooves' length and fractal analysis. On the selected region of interest within Nippur, we establish a link between geology and geophysics, namely between what is seen on the surface at visible to infrared wavelengths, and Ganymede's shallow subsurface, which is still largely unknown today. To do so, we analyse the grooves' length and spatial distribution to estimate the potential thickness of the icy crust above the deep ocean required to develop the grooves. A fractal approach, namely a self-similar clustering method, allows us to determine the maximum depth at which grooves can penetrate the icy subsurface [3, 4]. As a result, the grooves mapped in the Nippur Sulcus region in principle could penetrate the ice crust up to 130-145 km (Fig. 3).Fig. 3. A self-similar clustering method allows us to determine the maximum depth up to which grooves can penetrate the icy subsurface. To do this, we calcu-late an integral correlation coefficient within certain length ranges. In this plot, the x axis is the logarithm of these threshold lengths, while the y axis represents the logarithm of the correlation coefficient (on the left) and what is called the local slope (on the right, which is the point-by-point measurement of the slope of the tangent to the curve). As a result, the grooves mapped in the Nippur Sulcus region in principle could pene-trate the ice crust up to 130-145 km, which is in agreement with independent estimates of the average thickness of the icy shell.Simulation of radar surface scattering at RIME frequencies. The Radar for Icy Moon Exploration (RIME) is one of the payload instruments aboard the JUICE spacecraft [5]. Operating at a central frequency of 9 MHz, and transmitting either a 3-MHz or a 1-MHz bandwidth (corresponding to a range resolution in water ice of about 30 m and 90 m respectively), RIME is tasked to explore the subsurface of Ganymede, Europa and Callisto down to a depth of several kilometres. However, clutter noise from rougher terrains is a limiting factor in the detectability of deeper, weaker reflections from the subsurface. The application of a coherent model of surface scattering to a roughness model of Nippur Sulcus demonstrates that clutter decays much slower than on Mars for a Ganymede-like topography (Fig. 4), which creates a challenge for the scientific interpretation of future RIME data.Fig. 4. Radargram of simulated surface echoes pro-duced for a subset of Nippur Sulcus, for a 3-MHz bandwith pulse. The time delay of echoes has been converted to the depth in water ice from which a radar echo would have the same time delay. The radargrams have been cropped to show only the part of the echoes that is unaffected by the finite size of the pseudo-topographic model.Conclusions. The case of Nippur Sulcus is well suited to test what could be closely observed in the future by different instruments onboard the JUICE mission, combining remote sensing data probing the surface and theoretical modeling aimed at the geophysical study of the satellite's subsurface. The merits and issues brought to light by our study should be taken into account to achieve a broader understanding of the physical processes linking Ganymede's surface and subsurface. Acknowledgements: We acknowledge support from the research project: "Ganymede from 2D to 3D: A multidisciplinary approach in preparation for JUICE", selected in 2019 in the framework of an "INAF Mainstream" call.References: [1] Collins G. C., et al., Global geologic map of Ganymede: U.S. Geological Survey Scientific Investigations Map 3237, pamphlet 4 p., 1 sheet, scale 1:15,000,000 (2013). [2] Carlson R. W, et al., Space Sci. Rev. 60, 457-502 (1992). [3] Lucchetti A., Pozzobon R., Mazzarini F., Cremonese G., Massironi M. (2017). Icarus 297, 252-264. [4] Lucchetti A., Rossi C., Mazzarini F., Pajola M., Pozzobon R., Massironi M., Cremonese G. (2021). Planet. Space Sci. 195, article id. 105140. [5] Bruzzone L., Croci R. (2019). Proceedings of the 2019 IEEE 5th International Workshop on Metrology for AeroSpace, Turin (Italy), 19-21 June 2019

Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants

Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporters to heighten neurotransmitter availability extracellularly. Exacerbated dopamine signaling is particularly considered as a key determinant of psychostimulant action. Much less is known about possible adverse effects of these drugs on peripheral organs, and if in utero exposure induces lifelong pathologies. Here, we addressed this question by combining human RNA-seq data with cellular and mouse models of neuroendocrine development. We show that episodic maternal exposure to psychostimulants during pregnancy coincident with the intrauterine specification of pancreatic beta cells permanently impairs their ability of insulin production, leading to glucose intolerance in adult female but not male offspring. We link psychostimulant action specifically to serotonin signaling and implicate the sex-specific epigenetic reprogramming of serotonin-related gene regulatory networks upstream from the transcription factor Pet1/Fev as determinants of reduced insulin production.Peer reviewe

Forecasting the 2017/2018 seasonal influenza epidemic in England using multiple dynamic transmission models: a case study.

BACKGROUND: Since the 2009 A/H1N1 pandemic, Public Health England have developed a suite of real-time statistical models utilising enhanced pandemic surveillance data to nowcast and forecast a future pandemic. Their ability to track seasonal influenza and predict heightened winter healthcare burden in the light of high activity in Australia in 2017 was untested. METHODS: Four transmission models were used in forecasting the 2017/2018 seasonal influenza epidemic in England: a stratified primary care model using daily, region-specific, counts and virological swab positivity of influenza-like illness consultations in general practice (GP); a strain-specific (SS) model using weekly, national GP ILI and virological data; an intensive care model (ICU) using reports of ICU influenza admissions; and a synthesis model that included all data sources. For the first 12 weeks of 2018, each model was applied to the latest data to provide estimates of epidemic parameters and short-term influenza forecasts. The added value of pre-season population susceptibility data was explored. RESULTS: The combined results provided valuable nowcasts of the state of the epidemic. Short-term predictions of burden on primary and secondary health services were initially highly variable before reaching consensus beyond the observed peaks in activity between weeks 3-4 of 2018. Estimates for R0 were consistent over time for three of the four models until week 12 of 2018, and there was consistency in the estimation of R0 across the SPC and SS models, and in the ICU attack rates estimated by the ICU and the synthesis model. Estimation and predictions varied according to the assumed levels of pre-season immunity. CONCLUSIONS: This exercise successfully applied a range of pandemic models to seasonal influenza. Forecasting early in the season remains challenging but represents a crucially important activity to inform planning. Improved knowledge of pre-existing levels of immunity would be valuable

Characterization of the Surfaces and Near-Surface Atmospheres of Ganymede, Europa and Callisto by JUICE.

We present the state of the art on the study of surfaces and tenuous atmospheres of the icy Galilean satellites Ganymede, Europa and Callisto, from past and ongoing space exploration conducted with several spacecraft to recent telescopic observations, and we show how the ESA JUICE mission plans to explore these surfaces and atmospheres in detail with its scientific payload. The surface geology of the moons is the main evidence of their evolution and reflects the internal heating provided by tidal interactions. Surface composition is the result of endogenous and exogenous processes, with the former providing valuable information about the potential composition of shallow subsurface liquid pockets, possibly connected to deeper oceans. Finally, the icy Galilean moons have tenuous atmospheres that arise from charged particle sputtering affecting their surfaces. In the case of Europa, plumes of water vapour have also been reported, whose phenomenology at present is poorly understood and requires future close exploration. In the three main sections of the article, we discuss these topics, highlighting the key scientific objectives and investigations to be achieved by JUICE. Based on a recent predicted trajectory, we also show potential coverage maps and other examples of reference measurements. The scientific discussion and observation planning presented here are the outcome of the JUICE Working Group 2 (WG2): "Surfaces and Near-surface Exospheres of the Satellites, dust and rings"

Rationale for BepiColombo Studies of Mercury's Surface and Composition

BepiColombo has a larger and in many ways more capable suite of instruments relevant for determination of the topographic, physical, chemical and mineralogical properties of Mercury's surface than the suite carried by NASA's MESSENGER spacecraft. Moreover, BepiColombo's data rate is substantially higher. This equips it to confirm, elaborate upon, and go beyond many of MESSENGER's remarkable achievements. Furthermore, the geometry of BepiColombo's orbital science campaign, beginning in 2026, will enable it to make uniformly resolved observations of both northern and southern hemispheres. This will offer more detailed and complete imaging and topographic mapping, element mapping with better sensitivity and improved spatial resolution, and totally new mineralogical mapping. We discuss MESSENGER data in the context of preparing for BepiColombo, and describe the contributions that we expect BepiColombo to make towards increased knowledge and understanding of Mercury's surface and its composition. Much current work, including analysis of analogue materials, is directed towards better preparing ourselves to understand what BepiColombo might reveal. Some of MESSENGER's more remarkable observations were obtained under unique or extreme conditions. BepiColombo should be able to confirm the validity of these observations and reveal the extent to which they are representative of the planet as a whole. It will also make new observations to clarify geological processes governing and reflecting crustal origin and evolution. We anticipate that the insights gained into Mercury's geological history and its current space weathering environment will enable us to better understand the relationships of surface chemistry, morphologies and structures with the composition of crustal types, including the nature and mobility of volatile species. This will enable estimation of the composition of the mantle from which the crust was derived, and lead to tighter constraints on models for Mercury's origin including the nature and original heliocentric distance of the material from which it formed.Peer reviewe

Exploring the association between Alzheimer’s disease, oral health, microbial endocrinology and nutrition

Longitudinal monitoring of patients suggests a causal link between chronic periodontitis and the development of Alzheimer’s disease (AD). However, the explanation of how periodontitis can lead to dementia remains unclear. A working hypothesis links extrinsic inflammation as a secondary cause of AD. This hypothesis suggests a compromised oral hygiene leads to a dysbiotic oral microbiome whereby Porphyromonas gingivalis, a keystone periodontal pathogen, with its companion species, orchestrates immune subversion in the host. Brushing and chewing on teeth supported by already injured soft tissues leads to bacteraemias. As a result, a persistent systemic inflammatory response develops to periodontal pathogens. The pathogens, and the host’s inflammatory response, subsequently lead to the initiation and progression of multiple metabolic and inflammatory co-morbidities, including AD. Insufficient levels of essential micronutrients can lead to microbial dysbiosis through the growth of periodontal pathogens such as demonstrated for P. gingivalis under low hemin bioavailability. An individual’s diet also defines the consortium of microbial communities that take up residency in the oral and gastrointestinal (GI) tract microbiomes. Their imbalance can lead to behavioural changes. For example, probiotics enriched in Lactobacillus genus of bacteria, when ingested, exert some anti-inflammatory influence through common host/bacterial neurochemicals, both locally, and through sensory signalling back to the brain. Early life dietary behaviours may cause an imbalance in the host/microbial endocrinology through a dietary intake incompatible with a healthy GI tract microbiome later in life. This imbalance in host/microbial endocrinology may have a lasting impact on mental health. This observation opens up an opportunity to explore the mechanisms, which may underlie the previously detected relationship between diet, oral/GI microbial communities, to anxiety, cognition and sleep patterns. This review suggests healthy diet based interventions that together with improved life style/behavioural changes may reduce and/or delay the incidence of AD