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

T cell receptor can be recruited to a subset of plasma membrane rafts, independently of cell signaling and attendantly to raft clustering.

The constitutive/inducible association of the T cell receptor (TCR) with isolated detergent-resistant, lipid raft-derived membranes has been studied in Jurkat T lymphocytes. Membranes resistant to 1% Triton X-100 contained virtually no CD3epsilon, part of the TCR complex, irrespective of cell stimulation. On the other hand, membranes resistant either to a lower Triton X-100 concentration (i.e. 0.2%) or to the less hydrophobic detergent Brij 58 (1%) contained (i) a low CD3epsilon amount (approximate 2.7% of total) in resting cells and (ii) a several times higher amount of the TCR component, after T cell stimulation with either antigen-presenting cells or with phytohemagglutinin. It appeared that CD3/TCR was constitutively associated with and recruited to a raft-derived membrane subset because (i) all three membrane preparations contained a similar amount of the raft marker tyrosine kinase Lck but no detectable amounts of the conventional membrane markers, CD45 phosphatase and transferrin receptor; (ii) a larger amount of particulate membranes were resistant to solubilization with 0.2% Triton X-100 and Brij 58 than to solubilization with 1% Triton X-100; and (iii) higher cholesterol levels were present in membranes resistant to either the lower Triton X-100 concentration or to Brij 58, as compared with those resistant to 1% Triton X-100. The recruitment of CD3 to the raft-derived membrane subset appeared (i) to occur independently of cell signaling events, such as protein-tyrosine phosphorylation and Ca(2+) mobilization/influx, and (ii) to be associated with clustering of plasma membrane rafts induced by multiple cross-linking of either TCR or the raft component, ganglioside GM(1). We suggest that during T cell stimulation a lateral reorganization of rafts into polarized larger domains can determine the recruitment of TCR into these domains, which favors a polarization of the signaling cascade

Bone marrow stromal cell antigen 2 is a specific marker of type I IFN-producing cells in the naive mouse, but a promiscuous cell surface antigen following IFN stimulation.

Type I IFN-producing cells (IPC) are sentinels of viral infections. Identification and functional characterization of these cells have been difficult because of their small numbers in blood and tissues and their complex cell surface phenotype. To overcome this problem in mice, mAbs recognizing IPC-specific cell surface molecules have been generated. In this study, we report the identification of new Abs specific for mouse IPC, which recognize the bone marrow stromal cell Ag 2 (BST2). Interestingly, previously reported IPC-specific Abs 120G8 and plasmacytoid dendritic cell Ag-1 also recognize BST2. BST2 is predominantly specific for mouse IPC in naive mice, but is up-regulated on most cell types following stimulation with type I IFNs and IFN-gamma. The activation-induced promiscuous expression of BST2 described in this study has important implications for the use of anti-BST2 Abs in identification and depletion of IPC. Finally, we show that BST2 resides within an intracellular compartment corresponding to the Golgi apparatus, and may be involved in trafficking secreted cytokines in IPC

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

Lipid rafts and T cell receptor signaling: a critical re-evaluation

The current model suggesting that raft integrity is required for T cell activation is mostly (but not exclusively) based on the use of drugs, such as methyl-beta-cyclodextrin (M beta CD), that disorganize rafts and inhibit T cell receptor (TCR)-induced Ca2+ influx. Here we show that conditions that disrupt lipid raft integrity do not inhibit TCR triggering in Jurkat cells and normal T lymphocytes. Indeed, we found that the reported inhibition of TCR-induced Ca2+ influx by M beta CD treatment is mainly due to (a) nonspecific depletion of intracellular Ca2+ stores and (b) plasma membrane depolarization of T cells. When these side-effects are taken into account, raft disorganization does not alter TCR-dependent Ca2+ signaling. In line with these results, also TCR-induced tyrosine phosphorylation is not inhibited by dispersion of lipid rafts. By contrast, in the same conditions, Ca2+ signaling via the glycosylphosphatidylinositol (GPI)-anchored protein CD59 is totally abolished. These results indicate that, while signaling through GPI-anchored proteins requires lipid raft integrity, CD3-dependent TCR activation occurs independently of cholesterol extraction

The Balance between T Cell Receptor Signaling and Degradation at the Center of the Immunological Synapse Is Determined by Antigen Quality.

The role of the center of the immunological synapse (the central supramolecular activation cluster or cSMAC) is controversial. One model suggests that the role of the cSMAC depends on antigen quality and can both enhance signaling and receptor downregulation, whereas a second model proposes that the sole function of the cSMAC is to downregulate signaling. An important distinction between the models is whether signaling occurs in the cSMAC. Here, we demonstrate that at early time points, signaling occurs outside the cSMAC, but occurs in the cSMAC at later time points. Additionally, we show that cSMAC formation enhances the stimulatory potency of weak agonists for the TCR. Combined with previous studies showing that cSMAC formation decreases the signaling by strong agonists, our data support a model proposing that signaling and receptor degradation both occur in the cSMAC and that the balance between signaling and degradation in the synapse is determined by antigen quality