SUNSTORM 1/X-ray Flux Monitor for CubeSats (XFM-CS) : Instrument characterization and first results

SUNSTORM 1 CubeSat was launched to Sun-synchronous low Earth orbit on August 17 2021. The primary purpose of the mission is an in-orbit demonstration of X-ray Flux Monitor (XFM) instrument. XFM is an innovative solar X-ray spectrometer for measuring and characterizing solar flares, which are known to be linked to a variety of space weather phenomena. XFM represents a next generation of solar X-ray flux monitors. It is based on silicon drift detector technology, which provides several notable performance improvements over its predecessors, which are based on Si PIN detectors. Transversal electric field and lower output capacitance allow operation at much faster pulse processing shaping times, allowing the system to achieve about 10 times higher throughput without saturation while also making it less sensitive to the increase of leakage current due to high temperature and/or radiation damage. Thus, XFM instruments can cover a very wide dynamic range of solar X-ray emission from the most quiescent conditions to the strongest X-class solar flares, while maintaining good spectral resolution (Peer reviewe

Targeting the MAPK7/MMP9 axis for metastasis in primary bone cancer

Metastasis is the leading cause of cancer related death. This multistage process involves contribution from both tumour cells and the tumour stroma to release metastatic cells into the circulation. Circulating tumour cells (CTCs) survive circulatory cytotoxicity, extravasate and colonise secondary sites effecting metastatic outcome. Reprogramming the transcriptomic landscape is a metastatic hallmark but detecting underlying master regulators that drive pathological gene expression is a key challenge, especially in childhood cancer. Here we used whole tumour plus single cell RNA sequencing in primary bone cancer and CTCs to perform weighted gene co-expression network analysis to systematically detect coordinated changes in metastatic transcript expression. This approach with comparisons applied to data collected from cell line models, clinical samples and xenograft mouse models revealed MAPK7/MMP9 signalling as a driver for primary bone cancer metastasis. RNAi knockdown of MAPK7 reduces proliferation, colony formation, migration, tumour growth, macrophage residency/polarisation and lung metastasis. Parallel to these observations were reduction of activated interleukins IL1B, IL6, IL8 plus mesenchymal markers VIM and VEGF in response to MAPK7 loss. Our results implicate a newly discovered, multidimensional MAPK7/MMP9 signalling hub in primary bone cancer metastasis that is clinically actionable

Defective spermatogenesis and testosterone levels in kinase suppressor of Ras1 (KSR1)-deficient mice

The aim of this study was to clarify the role of the protein kinase suppressor of Ras1 (KSR1) in spermatogenesis. Spermatogenesis in ksr1 -/- mice was studied in testicular tissue and epididymal spermatozoa by light and transmission electron microscopy and by immunofluorescence using antibodies to ghrelin and 3β-hydroxysteroid dehydrogenase (3β-HSD). Blood testosterone levels were also assessed. ksr1 -/- mice showed reduced epididymal sperm concentration and motility as compared with wild-type (wt) mice. Testis tissue from ksr1 -/- mice revealed a prevalent spermatogenetic arrest at the spermatocyte stage; the interstitial tissue was hypertrophic and the cytoplasm of the Leydig cells was full of lipid droplets. Ghrelin signal was present in the seminiferous tubules and, particularly, in the interstitial tissue of wt mice; however, in ksr1 -/- mice ghrelin expression was very weak in both the interstitial tissue and tubules. On the contrary, the signal of 3β-HSD was weak in the interstitial tissue of wt and strong in ksr1 -/- mice. Testosterone levels were significantly increased in the blood of ksr1 -/- mice (P < 0.05) as compared with wt. The results obtained reveal the importance of the KSR scaffold proteins in the spermatogenetic process. The study of the molecular mechanisms associated with spermatogenetic defects in a mouse model is essential to understand the factors involved in human spermatogenesis

Chlamidia Psittaci nel colombo da città: aspetti anatomo-patologici, sierologici e biomolecolari

In this study we evaluate the prevalence of Chlamydiaceae, especially C. psittaci, in synanthropic birds such as urban pigeons in some areas of Venice. Innovative molecular tools, such as microarray and MLVA (Multilocus VNTR Assay), were applied in order to evaluate the genotypes of C. psittaci and the other species of Chlamydia present in this avian population to assess the risk of zoonosis posed by pigeons in this urban area. Moreover, we classified and correlated the gross- pathological lesions with the pathogen. Our results showed the presence of C. psittaci in urban population of pigeons in Venice, with a prevalence of 10%. We also demonstrated an atypical strain of C. psittaci not yet classified with the available laboratory techniques. Genotyping revealed the presence of genotypes B, E and E/B that could be considered less frequently involved in cases of human infection. Additionally, we found other Chlamydia strains suggesting the presence of a new Chlamydia genotype. Finally, the elaboration of the data, collected during the first and second sampling phase, revealed a correlation between C. psittaci and adult females pigeons, presenting hepatomegaly. Based on this results we develop and adopted a diagnostic protocol during necropsy that allows to select pigeons, which have a higher probability to be infected, and a better organization and management of interests samples, containing the economic costs and maintaining high-level of the diagnostic standards

Diacylglycerol activates the influx of extracellular cations in T lymphocytes independently of intracellular calcium store depletion and possibly involving endogenous TRP6 gene products

n Jurkat and human peripheral blood T-lymphocytes, 1-oleoyl-2-acetyl-sn-glycerol (OAG), a membrane-permeant analogue of diacylglycerol, activated the influx of Ca(2+), Ba(2+) and Sr(2+). OAG also caused plasma-membrane depolarization in Ca(2+)-free media that was recovered by the addition of bivalent cation, indicating the activation of Na(+) influx. OAG-induced cation influx was (i) mimicked by the natural dacylglycerol 1-stearoyl-2-arachidonyl-sn-glycerol, (ii) not blocked by inhibiting protein kinase C or in the absence of phospholipase C activity and (iii) blocked by La(3+) and Gd(3+). Differently from OAG, both thapsigargin and phytohaemagglutinin activated a potent influx of Ca(2+), but little influx of Ba(2+) and Sr(2+). Moreover, the influx of Ca(2+) activated by thapsigargin and that activated by OAG were additive. Furthermore, several drugs (i.e. econazole, SKF96365, carbonyl cyanide p-trifluoromethoxyphenylhydrazone, 2-aminoethoxy diphenylborate and calyculin-A), while inhibiting the influx of Ca(2+) induced by both thapsigargin and phytohaemagglutinin, did not affect OAG-stimulated cation influx. Transient receptor potential (TRP) 3 and TRP6 proteins have been shown previously to be activated by diacylglycerol when expressed heterologously in animal cells [Hofmann, Obukhov, Schaefer, Harteneck, Gudermann and Schultz (1999) Nature (London) 397, 259-263]. In both Jurkat and peripheral blood T-lymphocytes, mRNA encoding TRP proteins 1, 3, 4 and 6 was detected by reverse transcriptase PCR, and the TRP6 protein was detected by Western blotting in a purified plasma-membrane fraction. We conclude that T-cells express a diacylglycerol-activated cation channel, unrelated to the channel involved in capacitative Ca(2+) entry, and associated with the expression of TRP6 protein

The KSR2-calcineurin complex regulates STIM1-ORAI1 dynamics and store-operated calcium entry (SOCE)

Store-operated calcium entry (SOCE) is the predominant Ca2+ entry mechanism in nonexcitable cells and controls a variety of physiological and pathological processes. Although significant progress has been made in identifying the components required for SOCE, the molecular mechanisms underlying it are elusive. The present study provides evidence for a direct involvement of kinase suppressor of Ras 2 (KSR2) in SOCE. Using lymphocytes and fibroblasts from ksr2 12/ 12 mice and shKSR2-depleted cells, we find that KSR2 is critical for the elevation of cytosolic Ca2+ concentration. Specifically, our results show that although it is dispensable for Ca2+-store depletion, KSR2 is required for optimal calcium entry. We observe that KSR2 deficiency affects stromal interaction molecule 1 (STIM1)/ORAI1 puncta formation, which is correlated with cytoskeleton disorganization. Of interest, we find that KSR2-associated calcineurin is crucial for SOCE. Blocking calcineurin activity impairs STIM1/ORAI1 puncta-like formation and cytoskeleton organization. In addition, we observe that calcineurin activity and its role in SOCE are both KSR2 dependent

Immune-Privileged Sites within Skeletal Muscle: Apoptosis of FasL-Transfected Myoblasts Prevents the Formation of FasL-Expressing Muscle Fibers In Vivo

It has been suggested that over-expression of FasL could provide immune-privileged sites where transfected genes or/and grafted cells could exert their therapeutic action without inducing an immune response. Given the good transfectability of skeletal muscle, such tissue has been considered as a prime candidate for FasL engineerization. However, attempts to create FasL-expressing myoblasts have so far generated conflicting results. In this paper we set out to further investigate such approach, both in vitro and in vivo. We have designed a chimeric expression plasmid in which the addition of a GFP moiety to the C-terminal of FasL coding sequence rendered the final protein incapable of inducing apoptosis. Such construct has then been used for in vitro and in vivo transfection of rat muscle cells and its effects were compared with those obtained with a plasmid expressing normal FasL. The vast majority of primary myoblasts transfected in vitro with the FasL-expressing plasmid underwent apoptosis within the first 48 hours. Conversely, transfections with the FasL-GFP plasmid failed to induce cell death and allowed the formation of FasL-GFP positive myotubes, thereby demonstrating the inability of the chimeric product to activate the FasL-Fas pathway. In vivo, muscles co-injected with LacZ- and FasL-encoding plasmids developed a leukocytes infiltrate and transfected fibers were rapidly cleared out. When muscles were injected with a mixture of FasL-GFP and LacZ plasmids, transfected fibers persisted for at least two weeks. The results presented here demonstrate that Fas-FasL interaction is responsible for both the apoptosis of FasL transfected myoblasts in vitro and disappearance of FasL-engineered muscle fibers in vivo when transfections are carried out in regenerating muscles. However, our findings also suggest that it might be possible to obtain FasL-engineered mature muscle fibers by appropriately regulating the expression of the exogenous DNA during muscle differentiation

The KSR2-calcineurin complex regulates STIM1-ORAI1 dynamics and Store-Operated Calcium Entry (SOCE).

Store-Operated Calcium Entry (SOCE) is the predominant Ca2+ entry mechanism in nonexcitable cells and controls a variety of physiological and pathological processes. Although significant progress has been made to identify the components required for SOCE, the molecular mechanisms underlying SOCE are still elusive. The present study provides evidence for a direct involvement of Kinase Suppressor of Ras 2 (KSR2) in SOCE. Using lymphocytes and fibroblasts from ksr2-/- mice and shKSR2 depleted cells we found that KSR2 is critical for the elevation of [Ca2+]i. Specifically, our results show that while it is dispensable for Ca2+ store depletion, KSR2 is required for optimal calcium entry. We observed that KSR2 deficiency affects STIM1/ORAI1 puncta formation, which is correlated to cytoskeleton disorganization. Interestingly, we found that KSR2-associated calcineurin is crucial for SOCE. Blocking calcineurin activity impaired STIM1/ORAI1 puncta-like formation and cytoskeleton organization. In addition, we observed that calcineurin activity and its role on SOCE were both KSR2-dependent.These findings identify KSR2 as a regulator of SOCE and reveal a new mechanism whereby the KSR2-calcineurin complex is crucial in the store dependent STIM1-ORAI1 dynamics