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Objective To determine the health status and exercise capacity of COVID-19 survivors one year after hospital discharge. Methods This multicenter prospective study included COVID-19 survivors 12 months after hospital discharge. Participants were randomly selected from a large cohort of COVID-19 patients who had been hospitalized until 15th April 2020. They were interviewed about persistent symptoms, underwent a physical examination, chest X-ray, and a 6-minute walk test (6MWT). A multivariate analysis was performed to determine the risk factors for persistent dyspnea. Results Of the 150 patients included, 58% were male and the median age was 63 (IQR 54–72) years. About 82% reported ≥1 symptoms and 45% had not recovered their physical health. The multivariate regression analysis revealed that the female sex, chronic obstructive pulmonary disease, and smoking were independent risk factors for persistent dyspnea. Approximately 50% completed less than 80% of the theoretical distance on the 6MWT. Only 14% had an abnormal X-ray, showing mainly interstitial infiltrates. A third of them had been followed up in outpatient clinics and 6% had undergone physical rehabilitation. Conclusion Despite the high rate of survivors of the first wave of the COVID-19 pandemic with persistent symptomatology at 12 months, the follow-up and rehabilitation of these patients has been really poor. Studies focusing on the role of smoking in the persistence of COVID-19 symptoms are lacking.

Cystatin B (CSTB) acts as an inhibitor of cysteine proteases of the cathepsin family and loss-of-function mutations result in human brain diseases with a genotype-phenotype correlation. In the most severe case, CSTB-deficiency disrupts brain development, and yet the molecular basis of this mechanism is missing. Here, we establish CSTB as a regulator of chromatin structure during neural stem cell renewal and differentiation. Murine neural precursor cells (NPCs) undergo transient proteolytic cleavage of the N-terminal histone H3 tail by cathepsins B and L upon induction of differentiation into neurons and glia. In contrast, CSTB-deficiency triggers premature H3 tail cleavage in undifferentiated self-renewing NPCs and sustained H3 tail proteolysis in differentiating neural cells. This leads to significant transcriptional changes in NPCs, particularly of nuclear-encoded mitochondrial genes. In turn, these transcriptional alterations impair the enhanced mitochondrial respiration that is induced upon neural stem cell differentiation. Collectively, our findings reveal the basis of epigenetic regulation in the molecular pathogenesis of CSTB deficiency.

SUMMARY Nuclear import receptors, also called importins, mediate nuclear import of proteins and chaperone aggregation-prone cargoes (e.g., neurodegeneration-linked RNA-binding proteins [RBPs]) in the cytoplasm. Importins were identified as modulators of cellular toxicity elicited by arginine-rich dipeptide repeat proteins (DPRs), an aberrant protein species found in C9orf72-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mechanistically, the link between importins and arginine-rich DPRs remains unclear. Here, we show that arginine-rich DPRs (poly-GR and poly-PR) bind directly to multiple importins and, in excess, promote their insolubility and condensation. In cells, poly-GR impairs Impα/β-mediated nuclear import, including import of TDP-43, an RBP that aggregates in C9orf72-ALS/FTD patients. Arginine-rich DPRs promote phase separation and insolubility of TDP-43 in vitro and in cells, and this pathological interaction is suppressed by elevating importin concentrations. Our findings suggest that importins can decrease toxicity of arginine-rich DPRs by suppressing their pathological interactions., In Brief Hutten et al. show that arginine-rich dipeptide repeat proteins (DPRs) associated with the neurodegenerative diseases ALS and FTD bind directly to importins, promote their condensation, and interfere with importin function. Elevated importin levels can shield arginine-rich DPRs and suppress DPR-induced phase separation of TDP-43 and RNA., Graphical Abstract

We establish cystatin B (CSTB) as a regulator of histone H3 tail clipping in murine neural progenitor cells (NPCs) and provide evidence suggesting that epigenetic dysregulation contributes to the early pathogenesis in brain disorders associated with deficient CSTB function. We show that NPCs undergo regulated cleavage of the N-terminal tail of histone H3 at threonine 22 (H3T22) transiently upon induction of differentiation. CSTB-deficient NPCs present premature activation of H3T22 clipping during self-renewal mediated by increased activity of cathepsins L and B. During differentiation, the proportion of immature committed neurons undergoing H3T22 clipping is significantly higher in CSTB-deficient than in wild-type NPCs, with no observable decline within 12 days post-differentiation. CSTB-deficient NPCs exhibit significant transcriptional changes highlighting altered expression of nuclear-encoded mitochondrial genes. These changes are associated with significantly impaired respiratory capacity of differentiating NPCs devoid of CSTB. Our data expand the mechanistic understanding of diseases associated with CSTB deficiency.

Ovarian cancer (OC) is the most lethal gynecologic cancer characterized by an elevated apoptosis resistance that, potentially, leads to chemo-resistance in the recurrent disease. Mitochondrial oxidative phosphorylation was found altered in OC, and mitochondria were proposed as a target for therapy. Molecular evidence suggests that the deregulation of mitochondrial biogenesis, morphology, dynamics, and apoptosis is involved in carcinogenesis. However, these mitochondrial processes remain to be investigated in OC. Eighteen controls and 16 OC tissues (serous and mucinous) were collected. Enzymatic activities were performed spectrophotometrically, mitochondrial DNA (mtDNA) content was measured by real-time-PCR, protein levels were determined by Western blotting, and mitochondrial number and structure were measured by electron microscopy. Statistical analysis was performed using Student’s t-test, Mann-Whitney U test, and principal component analysis (PCA). We found, in OC, that increased mitochondrial number associated with increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and mitochondrial transcription factor A (TFAM) protein levels, as well as mtDNA content. The OC mitochondria presented an increased maximum length, as well as reduced cristae width and junction diameter, associated with increased optic atrophy 1 protein (OPA1) and prohibitin 2 (PHB2) protein levels. In addition, in OC tissues, augmented cAMP and sirtuin 3 (SIRT3) protein levels were observed. PCA of the 25 analyzed biochemical parameters classified OC patients in a distinct group from controls. We highlight a “mitochondrial signature” in OC that could result from cooperation of the cAMP pathway with the SIRT3, OPA1, and PHB2 proteins.

This work presents the latest results of new technological concepts for large aperture, lightweight telescopes using thin deployable active mirrors. The study is originally addressed to a spaceborne DIAL (Differential Absorption Lidar) at 935.5 nm for the measurement of water vapour profile in atmosphere, as an output of an ESA contract (whose preliminary results were presented at ICSO 2006). The high versatility of these concepts allows to exploit the presented technology for any project willing to consider large aperture, segmented lightweight telescopes. A possible scientific application is for Ultra High Energy Cosmic Rays detection through the fluorescence traces in atmosphere and diffused Cerenkov signals observation via a Schmidt-like spaceborne LEO telescope with large aperture, wide Field of View (FOV) and low f/#. A technology demonstrator has been manufactured and tested in order to investigate two project critical areas identified during the preliminary design: the performances of the long-stroke actuators used to implement the mirror active control and the mirror survivability to launch. In particular, this breadboard demonstrates at first that the mirror actuators are able to control with the adequate accuracy the surface shape and to recover a deployment error with their long stroke; secondly, the mirror survivability has been demonstrated using an electrostatic locking between mirror and backplane able to withstand without failure a vibration test representative of the launch environment.

This work presents a new technological concept for large aperture, lightweight, telescopes using thin deployable active mirrors, currently under a feasibility study for spaceborne Lidars. The study is mainly addressed to a DIAL (Differential Absorption Lidar) at 935.5 nm for the measurement of water vapour profile in atmosphere, to be part of a typical small ESA Earth Observation satellite to be launched with ROCKOT vehicle. A detailed telescope optical design will be presented, including the results of angular and spatial resolution, effective optical aperture and radiometric transmission, optical alignment tolerances, stray-light and baffling. Also the results of a complete thermo-mechanical model will be shown, discussing temporal and thermal stability, deployment technology and performances, overall mass budget, technological and operational risk and system complexity.

New technologies are proposed for large aperture and wide Field of View (FOV) space telescopes dedicated to detection of Ultra High Energy Cosmic Rays and Neutrinos flux, through observation of fluorescence traces in atmosphere and diffused Cerenkov signals. The presented advanced detection system is a spaceborne LEO telescope, with better performance than ground-based observatories, detecting up to 103 - 104 events/year. Different design approaches are implemented, all with very large FOV and focal surface detectors with sufficient segmentation and time resolution to allow precise reconstructions of the arrival direction. In particular, two Schmidt cameras are suggested as an appropriate solution to match most of the optical and technical requirements: large FOV, low f/#, reduction of stray light, optionally flat focal surface, already proven low-cost construction technologies. Finally, a preliminary proposal of a wideFOV retrofocus catadioptric telescope is explained.

Aim of this work is to propose an innovative star tracker, practically insensitive to the radiation coming from the sun or from other strong planetary sources out of (but near) the Field of View. These sources need to be stopped in some way. The classical solution to reject the unwanted radiation is to place a shadow (or baffle) before the star tracker objective. The shadow size depends on the Field of View and on the minimum angle subtended by the source (i.e. the sun) with respect to the optical axis of the star tracker. The lower is this angle the larger is the shadow. Requests for star trackers able to work with the sun as close as possible to the Field of View are increasing, due to the need of maximum mission flexibility. The innovation of this proposed star tracker is conceived by using spatial filtering with a concept complementary to that of coronagraph for sun corona observation, allowing to drastically reduce the size of the shadow. It can also work close to antennas and other part of the platform, which, when illuminated by the sun, become secondary sources capable to blind the star tracker. This kind of accommodation offers three main advantages: no cumbersome shadows (baffle), maximum flexibility in terms of mission profile, less platform location constraints. This new star sensor concept, dated 2007, is now patent pending. Galileo Avionica (now Selex Galileo) is the owner of the patent.

The increasing interest on space telescopes for scientific applications leads to implement the manufacturing technology of the most critical element, i.e. the primary mirror: being more suitable a large aperture, it must be lightweight and deployable. The presented topic was originally addressed to a spaceborne DIAL (Differential Absorption LIDAR) mission operating at 935.5 nm for the measurement of water vapour profile in atmosphere, whose results were presented at ICSO 2006 and 2008. Aim of this paper is to present the latest developments on the main issues related to the fabrication of a breadboard, covering two project critical areas identified during the preliminary studies: the design and performances of the long-stroke actuators used to implement the mirror active control and the mirror survivability to launch via Electrostatic Locking (EL) between mirror and backplane. The described work is developed under the ESA/ESTEC contract No. 22321/09/NL/RA. The lightweight mirror is structured as a central sector surrounded by petals, all of them actively controlled to reach the specified shape after initial deployment and then maintained within specs for the entire mission duration. The presented study concerns: a) testing the Carbon Fiber Reinforced Plastic (CFRP) backplane manufacturing and EL techniques, with production of suitable specimens; b) actuator design optimisation; c) design of the deployment mechanism including a high precision latch; d) the fabrication of thin mirrors mock-ups to validate the fabrication procedure for the large shells. The current activity aims to the construction of an optical breadboard capable of demonstrating the achievement of all these coupled critical aspects: optical quality of the thin shell mirror surface, actuators performances and back-plane - EL subsystem functionality.

The final optical design for a space-borne light detection and ranging (lidar) mission is presented, in response to the European Space Agency "Advanced lidar concepts" proposal for use of a differential absorption lidar system to measure water vapor distribution in atmosphere at 935.5 nm. The telescope adopts a double afocal concept (i.e., four reflections with two mirrors) using a lightweight and large aperture primary mirror. It is derived from a feasibility study that compares several different optical configurations, taking into account parameters such as cost, dimensions, complexity, and technological feasibility. The final telescope optical design is described in detail, highlighting a trade-off with other solutions and its optical tolerances.

This paper describes an innovative approach for a new generation of large aperture, deployable telescopes for advanced space LIDAR applications, using the thin active mirror technology. The overall telescope design is presented with a special attention to the optical performances analysis. The mechanical layout with details of the deployment and baffling technique is shown; the complete satellite thermo-elastic analysis mapping the primary mirror deformation due to the thermal loads is presented; the control system architecture is explained and the optical design including the angular and spatial resolution, effective optical aperture and radiometric transmission, optical alignment tolerances, straylight and baffling is deeply discussed. Finally an overview of different mission profiles that this technology can satisfy is presented; the imaging performances can be achieved using the shown technology tuning the surface control to higher performances.

This feasibility study compares several optical configurations for an orbiting high resolution (

Three kinds of spectrometers based on off-axis Schmidt and Schmidt-Cassegrain cameras are presented; they have been used for several instruments studies, mainly for European Space Agency and Agenzia Spaziale Italiana. Both dispersive prism and grating based configurations have interesting characteristics, such as: simplicity, low cost, high efficiency, small volume and weight, very low sensitivity to polarization and great flexibility also in multichannel (wavebands) configurations. The image quality is high, even with low relative apertures and great fields of view, allowing a very good correction of smile and keystone. The compensation of the slit curvature induced by a prism disperser is also demonstrated. This family of spectrometers was the topic of three patents, belonging to Selex-Galileo, while the intellectual property belongs to A. Romali et al. C (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).