Причина возникновения нетравматических субарахноидальных кровоизлияний

СУБАРАХНОИДАЛЬНЫЕ КРОВОИЗЛИЯНИЯВНУТРИЧЕРЕПНЫЕ КРОВОИЗЛИЯНИЯГЕМОРРАГИИПАТОЛОГИЧЕСКИЕ ПРОЦЕССЫМОЗГОВОГО КРОВООБРАЩЕНИЯ РАССТРОЙСТВ

Conserving grey long-eared bats (Plecotus austriacus) in our landscape: a conservation management plan

The grey long-eared bat is one of the rarest bats in the UK, with a population estimated at 1,000 individuals and a distribution that is restricted mainly to the southern coast of England and Wales.Dr Orly Razgour's Conservation Management Plan outlines how the UK population is of high conservation concern because it appears to be declining and fragmented, and several maternity colonies have been lost in the past few decades.The decline of the grey long-eared bat in the UK is closely linked to the disappearance of lowland unimproved grasslands (meadows) its main foraging habitat. As such the grey long-eared bat is a good flagship species for the conservation of this threatened habitat

Pro-inflammatory cytokines in cystic glioblastoma: A quantitative study with a comparison with bacterial brain abscesses. With an MRI investigation of displacement and destruction of the brain tissue surrounding a glioblastoma

Cystic glioblastomas are aggressive primary brain tumors that may both destroy and displace the surrounding brain tissue as they grow. The mechanisms underlying these tumors’ destructive effect could include exposure of brain tissue to tumor-derived cytokines, but quantitative cytokine data are lacking. Here, we provide quantitative data on leukocyte markers and cytokines in the cyst fluid from 21 cystic glioblastomas, which we compare to values in 13 brain abscess pus samples. The concentration of macrophage/microglia markers sCD163 and MCP-1 was higher in glioblastoma cyst fluid than in brain abscess pus; lymphocyte marker sCD25 was similar in cyst fluid and pus, whereas neutrophil marker myeloperoxidase was higher in pus. Median cytokine levels in glioblastoma cyst fluid were high (pg/mL): TNF-α: 32, IL-6: 1064, IL-8: 23585, tissue factor: 28, the chemokine CXCL1: 639. These values were not significantly different from values in pus, pointing to a highly pro-inflammatory glioblastoma environment. In contrast, levels of IFN-γ, IL-1β, IL-2, IL-4, IL-10, IL-12, and IL-13 were higher in pus than in glioblastoma cyst fluid. Based on the quantitative data, we show for the first time that the concentrations of cytokines in glioblastoma cyst fluid correlate with blood leukocyte levels, suggesting an important interaction between glioblastomas and the circulation. Preoperative MRI of the cystic glioblastomas confirmed both destruction and displacement of brain tissue, but none of the cytokine levels correlated with degree of brain tissue displacement or peri-tumoral edema, as could be assessed by MRI. We conclude that cystic glioblastomas are highly pro-inflammatory environments that interact with the circulation and that they both displace and destroy brain tissue. These observations point to the need for neuroprotective strategies in glioblastoma therapy, which could include an anti-inflammatory approach

Genome-resolved metagenomics reveals role of iron metabolism in drought-induced rhizosphere microbiome dynamics

Recent studies have demonstrated that drought leads to dramatic, highly conserved shifts in the root microbiome. At present, the molecular mechanisms underlying these responses remain largely uncharacterized. Here we employ genome-resolved metagenomics and comparative genomics to demonstrate that carbohydrate and secondary metabolite transport functionalities are overrepresented within drought-enriched taxa. These data also reveal that bacterial iron transport and metabolism functionality is highly correlated with drought enrichment. Using time-series root RNA-Seq data, we demonstrate that iron homeostasis within the root is impacted by drought stress, and that loss of a plant phytosiderophore iron transporter impacts microbial community composition, leading to significant increases in the drought-enriched lineage, Actinobacteria. Finally, we show that exogenous application of iron disrupts the drought-induced enrichment of Actinobacteria, as well as their improvement in host phenotype during drought stress. Collectively, our findings implicate iron metabolism in the root microbiome’s response to drought and may inform efforts to improve plant drought tolerance to increase food security

Physical Properties of 7-Methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (mTBD)

7-Methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (mTBD) has useful catalytic properties and can form an ionic liquid when mixed with an acid. Despite its potential usefulness, no data on its thermodynamic and transport properties are currently available in the literature. Here we present the first reliable public data on the liquid vapor pressure (temperature from 318.23K to 451.2K and pressure from 11.1Pa to 10000Pa), liquid compressed density (293.15K to 473.15K and 0.092MPa to 15.788MPa), liquid isobaric heat capacity (312.48K to 391.50K), melting properties, liquid thermal conductivity (299.0K to 372.9K), liquid refractive index (293.15K to 343.15K), liquid viscosity (290.79K to 363.00K), liquid-vapor enthalpy of vaporization (318.23K to 451.2K), liquid thermal expansion coefficient (293.15K to 473.15K), and liquid isothermal compressibility of mTBD (293.15K to 473.15). The properties of mTBD were compared with those of other relevant compounds, including 1,5-diazabicyclo(4.3.0)non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and 1,1,3,3-tetramethylguanidine (TMG). We used the PC-SAFT equation of state to model the thermodynamic properties of mTBD, DBN, DBU, and TMG. The PC-SAFT parameters were optimized using experimental data.Peer reviewe

Brain metastases in patients with EGFR -mutated or ALK -rearranged non-small-cell lung cancers

Introduction—Brain metastases (BM) are common in non-small-cell lung cancer (NSCLC). However, the baseline incidence and evolution of BM over time in oncogene-driven NSCLCs are seldom reported. In this study, we evaluated the frequency of BM in patients with epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged NSCLC. Methods—The presence of BM, clinicopathologic data, and tumor genotype were retrospectively compiled and analyzed from a cohort of 381 patients. Results—We identified 86 EGFR-mutated (90.7% with metastatic disease; 85.9% received an EGFR inhibitor) and 23 ALK-rearranged (91.3% with metastatic disease; 85.7% received an ALK inhibitor) NSCLCs. BM were present in 24.4% of EGFR-mutated and 23.8% of ALK-rearranged NSCLCs at the time of diagnosis of advanced disease. This study did not demonstrate a difference in the cumulative incidence of BM over time between the two cohorts (EGFR/ALK cohort competing risk regression [CRR] coefficient of 0.78 [95% CI 0.44–1.39], p=0.41). In still living patients with advanced EGFR-mutated NSCLC, 34.2% had BM at 1 year, 38.4% at 2 years, 46.7% at 3 years, 48.7% at 4 years, and 52.9% at 5 years. In still living patients with advanced ALKrearranged NSCLC, 23.8% had BM at 1 year, 45.5% at 2 years, and 58.4% at 3 years. Conclusions—BM are frequent in advanced EGFR-mutated or ALK-rearranged NSCLCs, with an estimated >45% of patients with CNS involvement by three years of survival with the use of targeted therapies. These data point toward the CNS as an important unmet clinical need in the evolving schema for personalized care in NSCLC

The evolution of plasmid-carried antibiotic resistance

BACKGROUND: Antibiotic resistance represents a significant public health problem. When resistance genes are mobile, being carried on plasmids or phages, their spread can be greatly accelerated. Plasmids in particular have been implicated in the spread of antibiotic resistance genes. However, the selective pressures which favour plasmid-carried resistance genes have not been fully established. Here we address this issue with mathematical models of plasmid dynamics in response to different antibiotic treatment regimes. RESULTS: We show that transmission of plasmids is a key factor influencing plasmid-borne antibiotic resistance, but the dosage and interval between treatments is also important. Our results also hold when plasmids carrying the resistance gene are in competition with other plasmids that do not carry the resistance gene. By altering the interval between antibiotic treatments, and the dosage of antibiotic, we show that different treatment regimes can select for either plasmid-carried, or chromosome-carried, resistance. CONCLUSIONS: Our research addresses the effect of environmental variation on the evolution of plasmid-carried antibiotic resistance

The intramembrane protease Sppl2a is required for B cell and DC development and survival via cleavage of the invariant chain

The protease Sppl2a cleaves the N-terminal fragment of invariant chain (CD74) and is required for efficient B cell development and function.B cell development requires tight regulation to allow for the generation of a diverse repertoire while preventing the development of autoreactive cells. We report, using N-ethyl-N-nitrosourea (ENU)–induced mutagenesis, the identification of a mutant mouse (chompB) with a block in early B cell development. The blockade occurs after the transitional 1 (T1) stage and leads to a decrease in mature B cell subsets and deficits in T cell–dependent antibody responses. Additionally, chompB mice have decreases in myeloid dendritic cells (DCs). The mutation was mapped to the intramembrane protease signal peptide peptidase-like 2a (Sppl2a), a gene not previously implicated in immune cell development. Proteomic analysis identified the invariant chain (CD74) as a key substrate of Sppl2a and suggests that regulated intramembrane proteolysis of CD74 by Sppl2a contributes to B cell and DC survival. Moreover, these data suggest that modulation of Sppl2a may be a useful therapeutic strategy for treatment of B cell dependent autoimmune disorders