Karlssonclapp8844

Submesoscale structures fill the ocean surface, and recent numerical simulations and indirect observations suggest that they may extend to the ocean interior. It remains unclear, however, how far-reaching their impact may be-in both space and time, from weather to climate scales. Here transport pathways and the ultimate fate of the Irminger Current water from the continental slope to Labrador Sea interior are investigated through regional ocean simulations. Submesoscale processes modulate this transport and in turn the stratification of the Labrador Sea interior, by controlling the characteristics of the coherent vortices formed along West Greenland. Submesoscale circulations modify and control the Labrador Sea contribution to the global meridional overturning, with a linear relationship between time-averaged near surface vorticity and/or frontogenetic tendency along the west coast of Greenland, and volume of convected water. This research puts into contest the lesser role of the Labrador Sea in the overall control of the state of the MOC argued through the analysis of recent OSNAP (Overturning in the Subpolar North Atlantic Program) data with respect to estimates from climate models. It also confirms that submesoscale turbulence scales-up to climate relevance, pointing to the urgency of including its advective contribution in Earth systems models.Arthritis is a common manifestation of systemic lupus erythematosus (SLE) yet understanding of the underlying pathogenic mechanisms remains incomplete. We, therefore, interrogated gene expression profiles of SLE synovium to gain insight into the nature of lupus arthritis (LA), using osteoarthritis (OA) and rheumatoid arthritis (RA) as comparators. Knee synovia from SLE, OA, and RA patients were analyzed for differentially expressed genes (DEGs) and also by Weighted Gene Co-expression Network Analysis (WGCNA) to identify modules of highly co-expressed genes. Genes upregulated and/or co-expressed in LA revealed numerous immune/inflammatory cells dominated by a myeloid phenotype, in which pathogenic macrophages, myeloid-lineage cells, and their secreted products perpetuate inflammation, whereas OA was characterized by fibroblasts and RA of lymphocytes. Genes governing trafficking of immune cells into the synovium by chemokines were identified, but not in situ generation of germinal centers (GCs). Gene Set Variation Analysis (GSVA) confirmed activation of specific immune cell types in LA. Numerous therapies were predicted to target LA, including TNF, NFκB, MAPK, and CDK inhibitors. Detailed gene expression analysis identified a unique pattern of cellular components and physiologic pathways operative in LA, as well as drugs potentially able to target this common manifestation of SLE.Cryopreservation is a well-established method for bone storage. However, the ideal timing of mechanical testing after sacrificing the experimental animals is still under discussion and of significant importance to the presentation of accurate results. Therefore, the aim of this study was to investigate and compare different cryopreservation durations to native murine bone and whether there was an influence on mechanical bone testing. For this study the tibias of 57 female C57BL/6 mice-18-weeks of age-were harvested and randomly allocated to one of four groups with varying storage times (1) frozen at -80 °C for 3 months, (2) frozen at -80 °C for 6 months, (3) frozen at -80 °C for 12 months and (4) native group. MMAE datasheet The native group was immediately tested after harvesting. The comparison of the mean strength and load to failure rates demonstrated a significant difference between the storage groups compared to the native control (p = 0.007). However, there was no difference in the strength and the load to failure values of bones of all storage groups when compared against each other. link2 Once cryopreservation at -80 °C is performed, no differences of mechanical bone properties are seen up to 12 months of storage. When actual in vivo data is of close interest, immediate testing should be considered and is preferred. If comparison of groups is required and long-time storage is necessary, cryopreservation seems to be an accurate method at present.The mechanism of catalysis by the L-glutaminase-asparaginase from Pseudomonas 7A (PGA) was investigated using structural, mass spectrometry, and kinetic data. We had previously proposed mechanism of hydrolysis of L-Asn by the type II L-asparaginase from E. coli (EcAII), but that work was limited to just one enzyme. Based on results presented in this report, we postulate that all homotetrameric L-asparaginases from mesophilic bacteria utilize a common ping-pong mechanism of catalysis consisting of two subsequent nucleophilic substitutions. Several new structures of non-covalent complexes of PGA with different substrates, as well as structures of covalent acyl-enzyme intermediates of PGA with canonical substrates (L-Asp and L-Glu) and an opportunistic ligand, a citrate anion, were determined. The results of kinetic experiments monitored by high-resolution LC/MS, when combined with new structural data, clearly show that the reaction catalyzed by L-glutaminase-asparaginases proceeds through formation of a covalent intermediate, as observed previously for EcAII. Additionally, by showing that the same mechanism applies to L-Asn and L-Gln, we postulate that it is common for all these structurally related enzymes.All gibbon species (Primates Hylobatidae) are facing high extinction risk due to habitat loss and hunting. The Hainan gibbon Nomascus hainanus is the world's most critically endangered primate, and one of the priority conservation actions identified is to establish artificial canopy corridors to reconnect fragmented forests. The effectiveness of artificial canopy bridge as a conservation tool for wild gibbons has not been widely tested, and the results are rarely published. We constructed the first canopy bridge for Hainan gibbon in 2015 to facilitate passage at a natural landslide; mountaineering-grade ropes were tied to sturdy trees with the help of professional tree climbers and a camera trap was installed to monitor wildlife usage. Hainan gibbon started using the rope bridge after 176 days, and usage frequency increased with time. All members in the gibbon group crossed the 15.8 m rope bridge except adult male. Climbing was the predominant locomotor mode followed by brachiation. This study highlights the use and value of rope bridges to connect forest gaps for wild gibbons living in fragmented forests. While restoring natural forest corridors should be a priority conservation intervention, artificial canopy bridges may be a useful short-term solution.Since the end of the Little Ice Age, the west face of the Drus (Mont Blanc massif, France) has been affected by a retrogressive erosion dynamic marked by large rockfall events. From the 1950s onwards, the rock failure frequency gradually increased until the large rockfall event (292,680 m3) of June 2005, which made the Bonatti Pillar disappear. Aiming to characterize the rock failure activity following this major event, which may be related to permafrost warming, the granitic rock face was scanned each autumn between October 2005 and September 2016 using medium- and long-range terrestrial laser scanners. All the point clouds were successively compared to establish a rockfall source inventory and determine a volume-frequency relationship. Eleven years of monitoring revealed a phase of rock failure activity decay until September 2008, a destabilization phase between September 2008 and November 2011, and a new phase of rock failure activity decay from November 2011 to September 2016. The destabilization phase wack collapsed from the Drus west face, indicating a very high rock wall retreat rate of 14.4 mm year-1 over a surface of 266,700 m2. Averaged over a time window of 1000 years, the long-term retreat rate derived from the frequency density integration of rock failure volumes is 2.9 mm year-1. Despite difficulty in accessing and monitoring the site, our study demonstrates that long-term surveys of high-elevation rock faces are possible and provide valuable information that helps improve our understanding of landscape evolution in mountainous settings subject to permafrost warming.Spinal muscular atrophy (SMA) is a motor neuron disease, typically resulting from loss-of-function mutations in the survival motor neuron 1 (SMN1) gene. Nusinersen/SPINRAZA, a splice-switching oligonucleotide that modulates SMN2 (a paralog of SMN1) splicing and consequently increases SMN protein levels, has a therapeutic effect for SMA. link3 Previously reported small-molecule SMN2 splicing modulators such as risdiplam/EVRYSDI and its analog SMN-C3 modulate not only the splicing of SMN2 but also that of secondary splice targets, including forkhead box protein M1 (FOXM1). Through screening SMA patient-derived fibroblasts, a novel small molecule, designated TEC-1, was identified that selectively modulates SMN2 splicing over three secondary splice targets. TEC-1 did not strongly affect the splicing of FOXM1, and unlike risdiplam, did not induce micronucleus formation. In addition, TEC-1 showed higher selectively on galactosylceramidase and huntingtin gene expression compared to previously reported compounds (e.g., SMN-C3) due to off-target effects on cryptic exon inclusion and nonsense-mediated mRNA decay. Moreover, TEC-1 significantly ameliorated the disease phenotype in an SMA murine model in vivo. Thus, TEC-1 may have promising therapeutic potential for SMA, and our study demonstrates the feasibility of RNA-targeting small-molecule drug development with an improved tolerability profile.BNip1, which functions as a t-SNARE component of the syntaxin18 complex, is localized on the ER membrane and regulates retrograde transport from Golgi to the ER. BNip1 also has a BH3 domain, which generally releases pro-apoptotic proteins from Bcl2-mediated inhibition. Previously we reported that retinal photoreceptors undergo BNip1-dependent apoptosis in zebrafish β-snap1 mutants. Here, we investigated physiological roles of BNip1-dependent photoreceptor apoptosis. First, we examined the spatio-temporal profile of photoreceptor apoptosis in β-snap1 mutants, and found that apoptosis occurs only during a small developmental window, 2-4 days-post-fertilization (dpf), in which an apical photoreceptive membrane structure, called the outer segment (OS), grows rapidly. Transient expression of β-SNAP1 during this OS growing period prevents photoreceptor apoptosis in β-snap1 mutants, enabling cone to survive until at least 21 dpf. These observations suggest that BNip1-mediated apoptosis is linked to excessive activation of vesicular transport associated with rapid growth of the OS. Consistently, knockdown of Ift88 and Kif3b, which inhibits protein transport to the OS, rescued photoreceptor apoptosis in β-snap1 mutants. Treatment with rapamycin, which inhibits protein synthesis via the mTOR pathway, also rescued photoreceptor apoptosis in β-snap1 mutants. These data suggest that BNip1 performs risk assessment to detect excessive vesicular transport in photoreceptors.Impella CP is a percutaneously inserted left ventricular assist device indicated for temporary mechanical cardiac support during high risk percutaneous coronary interventions and for cardiogenic shock. The potential application of Impella has become particularly relevant during the current COVID-19 pandemic, for patients with acute severe heart failure complicating viral illness. Standard implantation of the Impella CP is performed under fluoroscopic guidance. Positioning of the Impella CP can be confirmed with transthoracic or transoesophageal echocardiography. We describe an alternative approach to guide intracardiac implantation of the Impella CP using two-dimensional and three-dimensional intracardiac echocardiography. This new technique can be useful in selected groups of patients when fluoroscopy, transthoracic and transoesophageal echocardiography is deemed inapplicable or limited for epidemiological or clinical reasons. Intracardiac three-dimensional echocardiography is a feasible alternative to the traditional techniques for implantation of an Impella CP device but careful consideration must be given to the potential limitations and complications of this technique.