When Is Domestic Political Unrest Related to International Conflict? Diversionary Theory and Japanese Foreign Policy, 1890–19411

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146888/1/j.1468-2478.2010.00620.x.pd

Differential activity of innate defense antimicrobial peptides against Nocardia species

<p>Abstract</p> <p>Background</p> <p>Members of the genus <it>Nocardia </it>are ubiquitous environmental saprophytes capable to cause human pulmonary, disseminated and cutaneous nocardiosis or bovine mastitis. Innate immunity appears to play an important role in early defense against <it>Nocardia </it>species. To elucidate the contribution of antimicrobial peptides (AMPs) in innate defense against <it>Nocardia</it>, the activity of human α-defensins human neutrophil peptides (HNPs) 1-3, human β-defensin (hBD)-3 and cathelicidin LL-37 as well as bovine β-defensins lingual and tracheal antimicrobial peptides (LAP, TAP) and bovine neutrophil-derived indolicidin against four important <it>Nocardia </it>species was investigated.</p> <p>Results</p> <p>Whereas <it>N. farcinica </it>ATCC 3318 and <it>N. nova </it>ATCC 33726 were found to be susceptible to all investigated human and bovine AMPs, <it>N. asteroides </it>ATCC 19247 was killed exclusively by neutrophil-derived human α-defensins HNP 1-3 and bovine indolicidin. <it>N. brasiliensis </it>ATCC 19296 was found to exhibit complete resistance to investigated human AMPs and to be susceptible only to bovine indolicidin.</p> <p>Conclusion</p> <p>Selected AMPs are capable to contribute to the first line of defense against <it>Nocardia</it>, yet, susceptibility appears to vary across different <it>Nocardia </it>species. Obtained results of neutrophil-derived AMPs to possess the broadest antinocardial spectrum are remarkable, since nocardiosis is characterized by a neutrophil-rich infiltrate <it>in vivo</it>.</p

Connected subglacial lake drainage beneath Thwaites Glacier, West Antarctica

We present conventional and swath altimetry data from CryoSat-2, revealing a system of subglacial lakes that drained between June 2013 and January 2014 under the central part of Thwaites Glacier, West Antarctica (TWG). Much of the drainage happened in less than 6 months, with an apparent connection between three lakes spanning more than 130 km. Hydro-potential analysis of the glacier bed shows a large number of small closed basins that should trap water produced by subglacial melt, although the observed large-scale motion of water suggests that water can sometimes locally move against the apparent potential gradient, at least during lake-drainage events. This shows that there are important limitations in the ability of hydro-potential maps to predict subglacial water flow. An interpretation based on a map of the melt rate suggests that lake drainages of this type should take place every 20–80 years, depending on the connectivity of the water flow at the bed. Although we observed an acceleration in the downstream part of TWG immediately before the start of the lake drainage, there is no clear connection between the drainage and any speed change of the glacier

Simulating the processes controlling ice-shelf rift paths using damage mechanics

Rifts are full-thickness fractures that propagate laterally across an ice shelf. They cause ice-shelf weakening and calving of tabular icebergs, and control the initial size of calved icebergs. Here, we present a joint inverse and forward computational modeling framework to capture rifting by combining the vertically integrated momentum balance and anisotropic continuum damage mechanics formulations. We incorporate rift–flank boundary processes to investigate how the rift path is influenced by the pressure on rift–flank walls from seawater, contact between flanks, and ice mélange that may also transmit stress between flanks. To illustrate the viability of the framework, we simulate the final 2 years of rift propagation associated with the calving of tabular iceberg A68 in 2017. We find that the rift path can change with varying ice mélange conditions and the extent of contact between rift flanks. Combinations of parameters associated with slower rift widening rates yield simulated rift paths that best match observations. Our modeling framework lays the foundation for robust simulation of rifting and tabular calving processes, which can enable future studies on ice-sheet–climate interactions, and the effects of ice-shelf buttressing on land ice flow

Cross-linking of DNA through HMGA1 suggests a DNA scaffold

Binding of proteins to DNA is usually considered 1D with one protein bound to one DNA molecule. In principle, proteins with multiple DNA binding domains could also bind to and thereby cross-link different DNA molecules. We have investigated this possibility using high-mobility group A1 (HMGA1) proteins, which are architectural elements of chromatin and are involved in the regulation of multiple DNA-dependent processes. Using direct stochastic optical reconstruction microscopy (dSTORM), we could show that overexpression of HMGA1a-eGFP in Cos-7 cells leads to chromatin aggregation. To investigate if HMGA1a is directly responsible for this chromatin compaction we developed a DNA cross-linking assay. We were able to show for the first time that HMGA1a can cross-link DNA directly. Detailed analysis using point mutated proteins revealed a novel DNA cross-linking domain. Electron microscopy indicates that HMGA1 proteins are able to create DNA loops and supercoils in linearized DNA confirming the cross-linking ability of HMGA1a. This capacity has profound implications for the spatial organization of DNA in the cell nucleus and suggests cross-linking activities for additional nuclear proteins

Species-specific activity of antibacterial drug combinations

International audienceThe spread of antimicrobial resistance has become a serious public health concern, making once treatable diseases deadly again and undermining breakthrough achievements of modern medicine 1,2. Drug combinations can aid in fighting multi-drug resistant (MDR) bacterial infections, yet, are largely unexplored and rarely used in clinics. To identify general principles for antibacterial drug combinations and understand their potential, we profiled ~3,000 dose-resolved combinations of antibiotics, human-targeted drugs and food additives in 6 strains from three Gram-negative pathogens, Escherichia coli, Salmonella Typhimurium and Pseudomonas aeruginosa. Despite their phylogenetic relatedness, more than 70% of the detected drug-drug interactions are species-specific and 20% display strain specificity, revealing a large potential for narrow-spectrum therapies. Overall, antagonisms are more common than synergies and occur almost exclusively between drugs targeting different cellular processes, whereas synergies are more conserved and enriched in drugs targeting the same process. We elucidate mechanisms underlying this dichotomy and further use our resource to dissect the interactions of the food additive, vanillin. Finally, we demonstrate that several synergies are effective against MDR clinical isolates in vitro and during Galleria mellonella infections with one reverting resistance to the last-resort antibiotic, colistin

Early protein intake predicts functional connectivity and neurocognition in preterm born children

© 2021, The Author(s). Nutritional intake can promote early neonatal brain development in very preterm born neonates (\u3c 32 weeks’ gestation). In a group of 7-year-old very preterm born children followed since birth, we examined whether early nutrient intake in the first weeks of life would be associated with long-term brain function and neurocognitive skills at school age. Children underwent resting-state functional MRI (fMRI), intelligence testing (Wechsler Intelligence Scale for Children, 5th Ed) and visual-motor processing (Beery-Buktenica, 5th Ed) at 7 years. Relationships were assessed between neonatal macronutrient intakes, functional connectivity strength between thalamic and default mode networks (DMN), and neuro-cognitive function using multivariable regression. Greater functional connectivity strength between thalamic networks and DMN was associated with greater intake of protein in the first week (β = 0.17; 95% CI 0.11, 0.23, p \u3c 0.001) but lower intakes of fat (β = − 0.06; 95% CI − 0.09, − 0.02, p = 0.001) and carbohydrates (β = − 0.03; 95% CI − 0.04, − 0.01, p = 0.003). Connectivity strength was also associated with protein intake during the first month (β = 0.22; 95% CI 0.06, 0.37, p = 0.006). Importantly, greater thalamic-DMN connectivity strength was associated with higher processing speed indices (β = 26.9; 95% CI 4.21, 49.49, p = 0.02) and visual processing scores (β = 9.03; 95% CI 2.27, 15.79, p = 0.009). Optimizing early protein intake may contribute to promoting long-term brain health in preterm-born children