Soluble plasma thrombomodulin levels in patients with chronic myeloproliferative disorder.

The plasma levels of soluble thrombomodulin (TM) were measured in 44 patients with chronic myeloprolif erative disorder, 15 with polycythemia vera (PV), 29 with es sential thrombocythemia (ET), and a group of 62 matched healthy controls. The younger patients had significantly lower TM levels (mean: 15.6 ± 4.8 ng/mL) than the older patients (mean: 28.6 ± 8.2 ng/mL, p < .001). Moreover, a significant negative correlation between platelet counts and plasma TM levels in healthy persons was noted (r = 0.317, p < .05). The only significant difference we found in plasma TM levels be tween patients and controls or among patients was between the young patients with ET (mean: 29.0 ± 19.2 ng/mL) and young healthy controls (mean: 15.6 ± 4.8 ng/mL). It is possible that younger ET patients with more active platelets are more sus ceptible to earlier vascular damage. The lack of any significant difference compared with the older patient population supports this hypothesis. Key Words: Thrombomodulin—Essential thrombocythemia—Polycythemia vera

Charge-transfer energy in iridates: A hard x-ray photoelectron spectroscopy study

We have investigated the electronic structure of iridates in the double perovskite crystal structure containing either Ir4+ or Ir5+ using hard x-ray photoelectron spectroscopy. The experimental valence band spectra can be well reproduced using tight-binding calculations including only the Ir 5d, O 2p, and O 2s orbitals with parameters based on the downfolding of the density-functional band structure results. We found that, regardless of the A and B cations, the A2BIrO6 iridates have essentially zero O 2p to Ir 5d charge-transfer energies. Hence double perovskite iridates turn out to be extremely covalent systems with the consequence being that the magnetic exchange interactions become very long ranged, thereby hampering the materialization of the long-sought Kitaev physics. Nevertheless, it still would be possible to realize a spin-liquid system using the iridates with a proper tuning of the various competing exchange interactions

C/EBPβ-Thr217 Phosphorylation Signaling Contributes to the Development of Lung Injury and Fibrosis in Mice

mice are refractory to Bleomycin-induced lung fibrosis the molecular mechanisms remain unknown. Here we show that blocking the ribosomal S-6 kinase (RSK) phosphorylation of the CCAAT/Enhancer Binding Protein (C/EBP)-β on Thr217 (a RSK phosphoacceptor) with either a single point mutation (Ala217), dominant negative transgene or a blocking peptide containing the mutated phosphoacceptor ameliorates the progression of lung injury and fibrosis induced by Bleomycin in mice. mice with a cell permeant, C/EBPβ peptide that inhibits phosphorylation of C/EBPβ on Thr217 (40 µg instilled intracheally on day-2 and day-6 after the single Bleomycin dose) also blocked the progression of lung injury and fibrosis induced by Bleomycin. Phosphorylation of human C/EBPβ on Thr266 (human homologue phosphoacceptor) was induced in collagen-activated human lung fibroblasts in culture as well as in activated lung fibroblasts in situ in lungs of patients with severe lung fibrosis but not in control lungs, suggesting that this signaling pathway may be also relevant in human lung injury and fibrosis.These data suggest that the RSK-C/EBPβ phosphorylation pathway may contribute to the development of lung injury and fibrosis

The SSDC Role in the LICIACube Mission: Data Management and the MATISSE Tool

Light Italian Cubesat for Imaging of Asteroids (LICIACube) is an Italian mission managed by the Italian Space Agency (ASI) and part of the NASA Double Asteroid Redirection Test (DART) planetary defense mission. Its main goals are to document the effects of the DART impact on Dimorphos, the secondary member of the (65803) Didymos binary asteroid system, characterizing the shape of the target body and performing dedicated scientific investigations on it. Within this framework, the mission Science Operations Center will be managed by the Space Science Data Center (ASI-SSDC), which will have the responsibility of processing, archiving, and disseminating the data acquired by the two LICIACube onboard cameras. In order to better accomplish this task, SSDC also plans to use and modify its scientific webtool Multi-purpose Advanced Tool for Instruments for the solar system Exploration (MATISSE), making it the primary tool for the LICIACube data analysis, thanks to its advanced capabilities for searching and visualizing data, particularly useful for the irregular shapes common to several small bodies

Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection

Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV pathogenesis. We have shown that STAT1 plays an important role in the severity of SARS-CoV pathogenesis and that it is independent of the role of STAT1 in interferon signaling. Mice lacking STAT1 have greater weight loss, severe lung pathology with pre-pulmonary-fibrosis-like lesions, and an altered immune response following infection with SARS-CoV. We hypothesized that STAT1 plays a role in the polarization of the immune response, specifically in macrophages, resulting in a worsened outcome. To test this, we created bone marrow chimeras and cell-type-specific knockouts of STAT1 to identify which cell type(s) is critical to protection from severe lung disease after SARS-CoV infection. Bone marrow chimera experiments demonstrated that hematopoietic cells are responsible for the pathogenesis in STAT1(−/−) mice, and because of an induction of alternatively activated (AA) macrophages after infection, we hypothesized that the AA macrophages were critical for disease severity. Mice with STAT1 in either monocytes and macrophages (LysM/STAT1) or ciliated lung epithelial cells (FoxJ1/STAT1) deleted were created. Following infection, LysM/STAT1 mice display severe lung pathology, while FoxJ1/STAT1 mice display normal lung pathology. We hypothesized that AA macrophages were responsible for this STAT1-dependent pathology and therefore created STAT1/STAT6(−/−) double-knockout mice. STAT6 is essential for the development of AA macrophages. Infection of the double-knockout mice displayed a lack of lung disease and prefibrotic lesions, suggesting that AA macrophage production may be the cause of STAT1-dependent lung disease. We propose that the control of AA macrophages by STAT1 is critical to regulating immune pathologies and for protection from long-term progression to fibrotic lung disease in a mouse model of SARS-CoV infection

Role of host genetics in fibrosis

Fibrosis can occur in tissues in response to a variety of stimuli. Following tissue injury, cells undergo transformation or activation from a quiescent to an activated state resulting in tissue remodelling. The fibrogenic process creates a tissue environment that allows inflammatory and matrix-producing cells to invade and proliferate. While this process is important for normal wound healing, chronicity can lead to impaired tissue structure and function

Anticipated Geological Assessment of the (65803) Didymos–Dimorphos System, Target of the DART–LICIACube Mission

On 2022 September 26, the DART spacecraft will impact the surface of Dimorphos, the ∼160 m size satellite of the binary near-Earth asteroid (NEA) (65803) Didymos. What will be observed on the surfaces of both asteroids and at the DART impact site is largely unknown, beyond the details of Didymos revealed by previous Arecibo and Goldstone radar observations. We present here the expected DART and LICIACube observations of the Didymos system and discuss the planned mapping strategies. By searching similar geological features and processes identified on other NEAs, we constrain the impact conditions that DART might encounter at Dimorphos, assessing both the asteroid's surface and interior structure

ANALOGUE SAMPLES IN AN EUROPEAN SAMPLE CURATION FACILITY - THE EURO-CARES PROJECT.

The objective of the H2020-funded EURO-CARES project (grant agreement n° 640190) was to create a roadmap for the implementation of a European Extraterrestrial Sample Curation Facility (ESCF) that would be suitable for the curation of samples from all possible return missions likely over the next few decades, i.e. from the Moon, asteroids and Mars. The return of extraterrestrial samples brought to Earth will require specific storage conditions and handling procedures, in particular for those coming from Mars. For practical reasons and sterility concerns it might be necessary for such a facility to have its own collection of analogue samples permitting the testing of storage conditions, and to develop protocols for sample prepartion and analyses. Within the framework of the EURO-CARES project, we havecreated a list of the different types of samples that would be relevant for such a curation facility. The facility will be used for receiving and opening of the returned sample canisters, as well as for handling and preparation of the returned samples. Furthermore, it will provide some analysis of the returned samples, i.e. early sample characterisation, and is expected to provide longterm storage of the returned samples. Each of these basic functions requires special equipment. Equipment, handling protocols and long-term storage conditions will strongly depend on the characteristics of the materials, and on whether returned samples are from the Moon, Mars or an asteroidal body. Therefore the different types and aspects of analogue samples one need to be considered, i.e. the nature of the materials, which analogues are needed for what purpose, what mass is needed, and how should the analogue samples be stored within the facility. We distinguished five different types of anologue samples: analogue (s.s.), witness plate, voucher specimen, reference sample, and standard. Analogues are materials that have one or more physical or chemical properties similar to Earth-returned extraterrestrial samples. Reference samples are well-characterised materials with known physical and chemical properties used for testing. They may not necessarily be the same materials as the analogues defined above. Standards are internationally recognised, homogeneous materials with known physical and chemical properties that are used for calibration. They can also be used as reference samples in certain circumstances. They may be made of natural materials but are often produced artificially. A voucher specimen is a duplicate of materials used at any stage during sample acquisition, storage, transport, treatment etc., e.g. spacecraft materials (including solar panels), lubricants, glues, gloves, saws, drills, and others. In addition, Earth landing site samples (from the touch down site) would be necessary in case of doubtful analysis, even if normally this type of contamination is not expected. Finally, a witness plate is defined as material left in an area where work is being done to detect any biological, particulate, chemical, and/or organic contamination. It is a spatial and temporal document of what happens in the work area. Analogue materials could be solids (including ices), liquids or gases. These could contain biological (extant and/or exinct) and/or organic components. They could be natural materials, e.g. rocks or minerals, or could be manufactured, such as mixtures of different components, which may be biologically and/or organically doped. Analogues with appropriate sample size and nature will be well-suited for testing and training of sample handling procedures, and for transport protocols. The training of science and curation teams also requires reference samples and standards. Long-term storage needs special witness plates and voucher specimes. Developing and testing sample preparation protocols needs all sample types