A woman in her 30s who was being treated for a mental illness with several psychotropic drugs was admitted to the hospital after being found in a state of unconsciousness and respiratory arrest at ...home. She was pronounced dead 12 hours after she was discovered. Her autopsy revealed symmetrical hemorrhagic necrosis in the putamen on both sides of her cerebrum. Although many drugs were detected in her blood, all of those other than dextromethorphan (DXM) were within or below the therapeutic range. Her blood DXM was 1.73 μg/ml at admission and 1.61 μg/ml at autopsy, which were within the toxic range or coma-to-death range. The cause of death was diagnosed as DXM poisoning. DXM can cause hallucinations and euphoria if taken in excess, but since it is available as an over-the-counter drug at general pharmacies, an increasing number of young people are overdosing on it, mistakenly believing it to be a safe drug with few side effects. We believe that further social measures against DXM are necessary in Japan, such as disseminating correct knowledge in society and regulating over-the-counter sales.
Biomass-derived biodegradable fibers have attracted considerable attention as sustainable alternatives to petroleum-derived non-biodegradable synthetic fibers. Curdlan, a linear β-1,3-glucan, is a ...promising renewable resource that exhibits unique physicochemical properties owing to its triple-helical crystalline structure. The regenerated fibers of curdlan can be fabricated by wet spinning; these fibers exhibit excellent ductility but poor mechanical strength compared to other polysaccharides such as cellulose. In this study, a new post-treatment was developed to enhance the mechanical properties of regenerated curdlan fibers by exploiting their high ductility when swollen with water. Curdlan was dry-jet wet spun using an ionic liquid as the solvent and water as the coagulant. The regenerated fibers were subsequently post-drawn in water to a maximum of four times the original fiber length, followed by air-drying. The resultant fiber showed a 1.4-fold increase in the briefringence (Δn) value, which represents the orientation degree; moreover, the tensile strength was two times higher (20 cN tex‒1; 300 MPa) than that of the untreated fiber. It was also observed that an increase in the degree of post-drawing was more effective in enhancing the regenerated curdlan fiber than an increase in the initial draw ratio from 10 to 20 during wet spinning.
Abstract
Variability in the heat delivery by Circumpolar Deep Water (CDW) is responsible for modulating the basal melting of the Amundsen Sea ice shelves. However, the mechanisms controlling the CDW ...inflow to the region’s continental shelf remain little understood. Here, a high-resolution regional model is used to assess the processes governing heat delivery to the Amundsen Sea. The key mechanisms are identified by decomposing CDW temperature variability into two components associated with 1) changes in the depth of isopycnals heave (HVE), and 2) changes in the temperature of isopycnals water mass property changes (WMP). In the Dotson–Getz trough, CDW temperature variability is primarily associated with WMP. The deeper thermocline and shallower shelf break hinder CDW access to that trough, and CDW inflow is regulated by the uplift of isopycnals at the shelf break—which is itself controlled by wind-driven variations in the speed of an undercurrent flowing eastward along the continental slope. In contrast, CDW temperature variability in the Pine Island–Thwaites trough is mainly linked to HVE. The shallower thermocline and deeper shelf break there permit CDW to persistently access the continental shelf. CDW temperature in the area responds to wind-driven modulation of the water mass on-shelf volume by changes in the rate of inflow across the shelf break and in Ekman pumping-induced vertical displacement of isopycnals within the shelf. The western and eastern Amundsen Sea thus represent distinct regimes, in which wind forcing governs CDW-mediated heat delivery via different dynamics.
Ice shelves play a vital role in regulating loss of grounded ice and in supplying freshwater to coastal seas. However, melt variability within ice shelves is poorly constrained and may be ...instrumental in driving ice shelf imbalance and collapse. High‐resolution altimetry measurements from 2010 to 2016 show that Dotson Ice Shelf (DIS), West Antarctica, thins in response to basal melting focused along a single 5 km‐wide and 60 km‐long channel extending from the ice shelf's grounding zone to its calving front. If focused thinning continues at present rates, the channel will melt through, and the ice shelf collapse, within 40–50 years, almost two centuries before collapse is projected from the average thinning rate. Our findings provide evidence of basal melt‐driven sub‐ice shelf channel formation and its potential for accelerating the weakening of ice shelves.
Plain Language Summary
Ice shelves act as safety bands around the Antarctic ice sheet. Many ice shelves are currently thinning, leading to acceleration of the grounded ice behind. Here we show that ice shelves' thinning is stronger along a channel structure formed by the ocean circulation under the ice shelf. The thinning is 3 times higher than the ice shelf's average, hence leading to a more rapid weakening of the ice shelf. This study provides evidence of basal melt‐driven sub‐ice shelf channel formation and its potential for accelerating the weakening of ice shelves.
Key Points
High‐resolution surface elevation change shows channelized thinning, unabated from the grounding line up to the calving front
Thinning is related to channelized basal melting controlled by ocean circulation and cavity geometry
Process has been ongoing for over 25 years, thinning the shelf to 3 quarter of its original height, making it more vulnerable to collapse
The pathogenesis of sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) has not yet been fully elucidated. Growth arrest-specific 6 (Gas6) has marked effects on ...hemostasis and reduces inflammation through its interaction with receptor tyrosine kinases of the TAM family: Tyro3, Axl, and Mer. Here, we found that plasma concentrations of Gas6 and soluble Mer were greater in patients with severe sepsis or septic ALI/ARDS compared with those in normal healthy donors. To determine whether the Gas6-Mer axis was critical in the pathogenesis of ALI/ARDS, we investigated the effects of intravenous administration of the selective Mer inhibitor UNC2250 on lipopolysaccharide (LPS)-induced ALI in mouse models subjected to inhalation of LPS. UNC2250 markedly inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of Gas6 and Mer proteins, severe lung damage, and increased amounts of reactive oxygen species (ROS) in LPS-induced ALI in mice. In human pulmonary aortic endothelial cells, LPS induced decreases in the amounts of endothelial nitric oxide synthase, thrombomodulin, and vascular endothelial-cadherin, which was blocked by treatment with UNC2250. UNC2250 also inhibited the LPS-dependent increases in cell proliferation and enhanced apoptosis in HL-60 cells, a human neutrophil-like cell line, and RAW264.7 cells, a mouse monocyte/macrophage cell line. These data provide insights into the potential multiple beneficial effects of the Mer inhibitor UNC2250 as a therapeutic reagent to treat inflammatory responses in ALI/ARDS.
In this study, enzymatic synthesis was conducted using cellodextrin phosphorylase (CDP), sucrose phosphorylase (SP), and sucrose with 1-azido-1-deoxy-β-glucoside (β-glucosyl azide) as the acceptor in ...phosphate buffer at pH 7.0. This yielded cellulose oligomers (degree of polymerization, DP ≈ 10) with azido groups at the reducing end as a white precipitate. A suspension of cellulose microcrystals with exposed azido groups on the surface was obtained via dissolution and recrystallization of the synthetic products dispersed in water by heating. The flat, ribbon-like cellulose microcrystals were a crystalline form of cellulose II and were several micrometers in length and several hundred nanometers in width. The microcrystals were 5.1–5.2 nm thick, which is equivalent to the chain length of cellulose oligomers with DP ≈ 10. When the cellulose II microcrystal suspensions were dried under a horizontal static magnetic field of 8 T, oriented films were obtained, wherein the microcrystals were aligned three-dimensionally. Synchrotron X-ray diffraction studies of the films revealed that the easy and intermediate axes (
χ
1
and
χ
2
, respectively) of the cellulose II crystals corresponded approximately to the 1 1 0 and 1
1
¯
0 directions, respectively.
Post-transcriptional RNA editing modulates gene expression in a condition-dependent fashion. We recently discovered C-to-Ψ editing in Vibrio cholerae tRNA. Here, we characterize the biogenesis, ...regulation, and functions of this previously undescribed RNA editing process. We show that an enzyme, TrcP, mediates the editing of C-to-U followed by the conversion of U to Ψ, consecutively. AlphaFold-2 predicts that TrcP consists of two globular domains (cytidine deaminase and pseudouridylase) and a long helical domain. The latter domain tethers tRNA substrates during both the C-to-U editing and pseudouridylation, likely enabling a substrate channeling mechanism for efficient catalysis all the way to the terminal product. C-to-Ψ editing both requires and suppresses other modifications, creating an interdependent network of modifications in the tRNA anticodon loop that facilitates coupling of tRNA modification states to iron availability. Our findings provide mechanistic insights into an RNA editing process that likely promotes environmental adaptation.
α-1,3-glucan is a linear homopolymer produced through the enzymatic polymerization of sucrose using recombinant glucosyl transferase J (GtfJ) enzyme. Two series of α-1,3-glucan short- and long-chain ...mixed esters, namely α-1,3-glucan acetate hexanoate and α-1,3-glucan propionate hexanoate, with different ratios of short to long sidechains were synthesized via heterogeneous chemical esterification. α-1,3-glucan propionate hexanoate, with a stable crystalline structure, had a significantly higher melting temperature than α-1,3-glucan acetate hexanoate. Melt-spun fibers of both series of esters were successfully prepared at lower temperatures than those required for conventional α-1,3-glucan homo esters, without decreases in molecular weights. The tensile strength of melt-spun fibers increased as the proportion of the short sidechain increased, reaching 367 MPa (ratio of acetate to hexanoate groups of 2.2:0.8), which was much higher than α-1,3-glucan tripropionate with a tensile strength of 115 MPa. X-ray diffraction analyses indicate that this high tensile strength is due to the high orientation of the molecular chains.
Intranuclear proteins, including high mobility group box 1 (HMGB1) and histone H3, released from inflammatory cells activate platelets and the coagulation systems, leading to development of ...disseminated intravascular coagulation (DIC) in individuals with sepsis. These observations prompted us to hypothesize that HMGB1 and histone H3 liberated from leukemia cells undergoing apoptosis after chemotherapy might play a role in development of DIC. To test this hypothesis, we prospectively measured plasma levels of coagulation markers and intranuclear proteins in patients with newly diagnosed acute leukemia (
n
= 17) before and after chemotherapy. Ten of 17 patients were diagnosed with DIC at the time of diagnosis of leukemia. Serum levels of HMGB1 and histone H3 were significantly higher in patients with DIC than in non-DIC patients. Of note, seven patients developed DIC or experienced exacerbation of coagulopathy after administration of anti-leukemic agents. Intriguingly, an increase in levels of HMGB1 and histone H3 were detected in five of seven patients. These findings suggest that intranuclear proteins spontaneously released from leukemia cells may play a role in development of leukemia-related DIC. Additionally, remission induction chemotherapy causes apoptosis of leukemia cells, leading to forced release of intranuclear proteins, which may exacerbate coagulopathy.
The instability and accelerated melting of the Antarctic Ice Sheet are among the foremost elements of contemporary global climate change. The increased freshwater output from Antarctica is important ...in determining sea level rise, the fate of Antarctic sea ice and its effect on the Earth's albedo, ongoing changes in global deep-ocean ventilation, and the evolution of Southern Ocean ecosystems and carbon cycling. A key uncertainty in assessing and predicting the impacts of Antarctic Ice Sheet melting concerns the vertical distribution of the exported meltwater. This is usually represented by climate-scale models as a near-surface freshwater input to the ocean, yet measurements around Antarctica reveal the meltwater to be concentrated at deeper levels. Here we use observations of the turbulent properties of the meltwater outflows from beneath a rapidly melting Antarctic ice shelf to identify the mechanism responsible for the depth of the meltwater. We show that the initial ascent of the meltwater outflow from the ice shelf cavity triggers a centrifugal overturning instability that grows by extracting kinetic energy from the lateral shear of the background oceanic flow. The instability promotes vigorous lateral export, rapid dilution by turbulent mixing, and finally settling of meltwater at depth. We use an idealized ocean circulation model to show that this mechanism is relevant to a broad spectrum of Antarctic ice shelves. Our findings demonstrate that the mechanism producing meltwater at depth is a dynamically robust feature of Antarctic melting that should be incorporated into climate-scale models.
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