The systemic inflammatory response observed during acute graft-versus-host disease (aGVHD) is driven by proinflammatory cytokines, a 'cytokine storm'. The function of plasmin in regulating the ...inflammatory response is not fully understood, and its role in the development of aGVHD remains unresolved. Here we show that plasmin is activated during the early phase of aGVHD in mice, and its activation correlated with aGVHD severity in humans. Pharmacological plasmin inhibition protected against aGVHD-associated lethality in mice. Mechanistically, plasmin inhibition impaired the infiltration of inflammatory cells, the release of membrane-associated proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and Fas-ligand directly, or indirectly via matrix metalloproteinases (MMPs) and alters monocyte chemoattractant protein-1 (MCP-1) signaling. We propose that plasmin and potentially MMP-9 inhibition offers a novel therapeutic strategy to control the deadly cytokine storm in patients with aGVHD, thereby preventing tissue destruction.
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a rare neurodegenerative disease resulting from mutations in the colony stimulating factor 1 receptor gene. Accurate ...diagnosis can be difficult because the associated clinical and MR imaging findings are nonspecific. We present 9 cases with intracranial calcifications distributed in 2 brain regions: the frontal white matter adjacent to the anterior horns of the lateral ventricles and the parietal subcortical white matter. Thin-section (1-mm) CT scans are particularly helpful in detection due to the small size of the calcifications. These calcifications had a symmetric "stepping stone appearance" in the frontal pericallosal regions, which was clearly visible on reconstructed sagittal CT images. Intrafamilial variability was seen in 2 of the families, and calcifications were seen at birth in a single individual. These characteristic calcification patterns may assist in making a correct diagnosis and may contribute to understanding of the pathogenesis of leukoencephalopathy.
N-cadherin is a homophilic cell adhesion molecule that stabilizes excitatory synapses, by connecting pre- and post-synaptic termini. Upon NMDA receptor (NMDAR) activation by glutamate, ...membrane-proximal domains of N-cadherin are cleaved serially by a-disintegrin-and-metalloprotease 10 (ADAM10) and then presenilin 1(PS1, catalytic subunit of the γ-secretase complex). To assess the physiological significance of the initial N-cadherin cleavage, we engineer the mouse genome to create a knock-in allele with tandem missense mutations in the mouse N-cadherin/Cadherin-2 gene (Cdh2
, or GD) that confers resistance on proteolysis by ADAM10 (GD mice). GD mice showed a better performance in the radial maze test, with significantly less revisiting errors after intervals of 30 and 300 s than WT, and a tendency for enhanced freezing in fear conditioning. Interestingly, GD mice reveal higher complexity in the tufts of thorny excrescence in the CA3 region of the hippocampus. Fine morphometry with serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstruction reveals significantly higher synaptic density, significantly smaller PSD area, and normal dendritic spine volume in GD mice. This knock-in mouse has provided in vivo evidence that ADAM10-mediated cleavage is a critical step in N-cadherin shedding and degradation and involved in the structure and function of glutamatergic synapses, which affect the memory function.
Although the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these ...conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions.
A retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes.
Asymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n = 14) were significantly younger than those who did not (p = 0.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (p = 0.032); however, none of the parameters were associated with histologically confirmed granuloma formation.
Genitourinary granulomas mimicking recurrence of carcinoma may develop in nearly 10% of patients after intravesical BCG therapy. Most patients can be managed without potentially toxic antituberculosis therapy.
Aunque las complicaciones de la terapia intravesical con BCG están bien descritas, pocas veces se ha comunicado la formación posterior de granulomas genitourinarios asintomáticos, y su estrategia de tratamiento sigue siendo controvertida. El objetivo de este estudio es evaluar la tasa de incidencia de la formación de granulomas genitourinarios asintomáticos que imitan la recurrencia del cáncer de vejiga tras el tratamiento intravesical con el bacilo de Calmette-Guérin (BCG), así como identificar las estrategias de diagnóstico y tratamiento según las características de los pacientes.
Se realizó una revisión retrospectiva de 162 pacientes sometidos a terapia intravesical con BCG. En los pacientes que desarrollaron granulomas, se evaluó el intervalo de tiempo entre la instilación de BCG y el desarrollo del granuloma, la presencia de bacterias acidorresistentes en las muestras de patología, los resultados del cultivo/reacción en cadena de la polimerasa, las estrategias de tratamiento de las lesiones y los resultados clínicos.
Se desarrollaron masas genitourinarias asintomáticas en 14 pacientes, de los cuales 5 se sometieron a evaluaciones histológicas confirmando en todos los casos una inflamación granulomatosa. Los órganos afectados fueron el riñón, la vejiga, la próstata y el pene. Aunque cuatro de los cinco pacientes no recibieron tratamiento para los granulomas, a uno de ellos se le administró medicación antituberculosa para evitar el empeoramiento de la lesión durante el periodo perioperatorio de la cistoprostatectomía programada. Ninguno de los pacientes experimentó empeoramiento o recurrencia de las lesiones granulomatosas. Los pacientes que desarrollaron masas asintomáticas (n = 14) eran significativamente más jóvenes que aquellos en los que no se produjeron (p = 0,0076), y el análisis multivariante también mostró que la edad más joven se asociaba de forma independiente con el desarrollo de lesiones clínicamente sospechosas (p = 0,032); sin embargo, ninguno de los parámetros se asoció con la formación de granulomas confirmados histológicamente.
Los granulomas genitourinarios que imitan la recurrencia del carcinoma pueden desarrollarse en cerca de un 10% de los pacientes sometidos a terapia intravesical con BCG. En la mayoría de los casos, el manejo de los pacientes puede realizarse sin una terapia antituberculosa potencialmente tóxica.
Bacteria show remarkable adaptability under several stressful conditions by shifting themselves into a dormant state. Less is known, however, about the mechanism underlying the cell transition to ...dormancy. Here, we report that the transition to dormant states is mediated by one of the major toxin-antitoxin systems, RelEB, in a cell density-dependent manner in Escherichia coli K-12 MG1655. We constructed a strain, IKA121, which expresses the toxin RelE in the presence of rhamnose and lacks chromosomal relBE and rhaBAD. With this strain, we demonstrated that RelE-mediated dormancy is enhanced at high cell densities compared to that at low cell densities. The initiation of expression of the antitoxin RelB from a plasmid, pCA24N, reversed RelE-mediated dormancy in bacterial cultures. The activation of RelE increased the appearance of persister cells against β-lactams, quinolones, and aminoglycosides, and more persister cells appeared at high cell densities than at low cell densities. Further analysis indicated that amino acid starvation and an uncharacterized extracellular heat-labile substance promote RelE-mediated dormancy. This is a first report on the induction of RelE-mediated dormancy by high cell density. This work establishes a population-based dormancy mechanism to help explain E. coli survival in stressful environments.
Enterococcus faecium QU 50, a novel thermophilic l-lactic acid (LA) producing strain, was used in this study to ferment sugar mixtures into LA. Under the optimal fermentation conditions (50 degree C, ...pH 6.5), strain QU 50 could ferment both mixed glucose/xylose sugars with relaxed CCR and mixed cellobiose/xylose sugars simultaneously without CCR to produce homo l-LA. The activity of enzymes related to xylose metabolism was also investigated. In the cells grown in a medium containing cellobiose/xylose, the activity of xylose isomerase and xylulose kinase, was 3.22 and 1.91 times higher, respectively, as compared to that of cells grown in a glucose/xylose medium. Strain QU 50 produced 70.8 g L-1 of l-LA with a yield of 1.04 g g-1 and a productivity of 2.95 g L-1 h-1 from simulated energy cane hydrolysate in batch fermentation. Immobilisation of strain QU 50 improved the operational stability of open repeated fermentation (three cycles), resulting in 61.1-64.3 g L-1 of l-LA with a yield of 1.01-1.02 g g-1 and a productivity of 3.22-3.82 g L-1 h-1. Thus, an efficient and cost-effective fermentation system was successfully established for l-LA production from sugar mixtures.
Dissolved iron (dFe) transported by the Amur River greatly contributes to phytoplankton growth in the Sea of Okhotsk. Nevertheless, there has been little research on the source of dFe to rivers, ...especially in the Amur‐Mid Basin, which is situated in a sporadic permafrost area. In the Amur‐Mid Basin, permafrost generally exists in wetlands in flat valleys, and these permafrost wetlands could be a source of dFe to rivers. To assess the importance of permafrost wetlands for dFe export, we conducted a local survey on land and soil characteristics of wetlands, and moreover analyzed the chemical composition (dFe, dissolved organic carbon DOC, pH, and electrical conductivity EC) of 24 rivers with different watershed sizes in summer. As a result of local survey, the thickly accumulated peat soils in the permafrost wetland were almost saturated and rich in organic matter from the surface to a greater depth near the permafrost table. In addition, the coverage of such permafrost wetlands in watersheds showed significant positive correlations with dFe (r2 = 0.67, p = 1.7e−6) and DOC (r2 = 0.48, p = 1.8e−4) and a negative correlation with EC (r2 = 0.52, p = 7.7e−5). The dFe concentration was also correlated well with DOC concentration (r2 = 0.68, p = 7.3e−7) but not correlated with pH and watershed area. These findings are the first to indicate that permafrost wetlands in the Amur‐Mid Basin considerably contribute to dFe and DOC export to rivers, and their coverage primarily determines riverine dFe and DOC concentrations in summer.
Plain Language Summary
Dissolved iron (dFe) is a key factor that limits phytoplankton growth in the ocean. In the Amur‐Okhotsk ecosystems, dFe transported by the Amur River greatly contributes to phytoplankton growth in the Sea of Okhotsk; however, there has been little research on the dFe source to rivers, especially in the Amur‐Mid Basin, which is situated in a sporadic permafrost area. In this study, we focused on permafrost wetlands in the Amur‐Mid Basin and investigated the soil characteristics and the relationship between wetland coverage and dFe concentrations in 24 watersheds. Permafrost wetlands contain waterlogged and organic‐rich peat soils, and more importantly, their coverage clearly shows strong positive relationships with riverine dFe and dissolved organic carbon (DOC) concentrations. This is the first study to show that permafrost wetlands impact water chemistry in the Amur‐Mid Basin, primarily as sources of dFe and DOC.
Key Points
We provide water chemistry data from 24 rivers with different watershed sizes in the Amur‐Mid Basin during summer
dFe and dissolved organic carbon concentrations showed a significant positive correlation with the coverage of the permafrost wetland in the watersheds
Permafrost was confirmed underneath wetlands, and thickly accumulated peat soils were rich in organic matter
Si wafers are widely used as a substrate material for fabricating ICs. The quality of ICs depends on the quality of Si wafers. The chemo-mechanical grinding (CMG) with soft abrasive grinding wheels ...(SAGW) has been recently found to be a great potential process for machining Si wafers to generate superior surface quality at low cost. However, there have been very few studies on observing variation of topography of scratch/texture and understanding basic eliminating process of scratch/texture on the ground Si wafer. Furthermore, few reports on the variation of surface roughness and material removal rate (MRR) during CMG process and relationship between MRR and surface roughness during CMG process are presented. In this paper, a series of CMG experiments have been conducted to study the elimination process of artificial scratches created on etched Si surfaces and residual textures induced by SD1500 diamond wheel in CMG process, and to understand the topography variations of Si surfaces and some basic grinding characteristics during CMG process.
Measurements of sound propagation in narrow tubes Yazaki, T; Tashiro, Y; Biwa, T
Proceedings of the Royal Society. A, Mathematical, physical, and engineering sciences,
11/2007, Letnik:
463, Številka:
2087
Journal Article
Recenzirano
The propagation of sound in hollow tubes is a fundamental theme common to many areas of classical acoustics. Kirchhoff's theory explaining the propagation of sound in a circular tube is now playing ...an important role as a starting point in studying sound in porous media. This paper reports on measurements of the phase velocity and attenuation coefficient in the narrow regions of tubes, where the sound undergoes anomalous dispersion and is seen to slow down remarkably to the extent that a runner can pass ahead of it. Kirchhoff's theory can be verified by experiment over a wide range of thermodynamical conditions, from isentropic to isothermal.
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