We made use of the two latest sets of rotation measures (RMs) of extragalactic radio sources, namely the NRAO VLA Sky Survey rotation measures catalog and a compilation by Kronberg and Newton-McGee, ...to infer the global structure of the Galactic magnetic field (GMF). We have checked that these two data sets are mutually consistent. Given the existence of clear patterns in the all-sky RM distributions we considered GMF models consisting of two components: disk (spiral or ring) and halo. The parameters of these components were determined by fitting different model field geometries to the observed RMs. We found that the model consisting of a symmetric (with respect to the Galactic plane) spiral disk and antisymmetric halo fits the data best and reproduces the observed distribution of RMs over the sky very well. We confirm that ring disk models are disfavored. Our results favor small pitch angles around ~ -- 5? and an increased vertical scale of electron distribution, in agreement with some recent studies. Based on our fits, we select two benchmark models suitable for studies of cosmic ray propagation, including cosmic rays at ultrahigh energies.
Isolated linear carbon chains (LCCs) encapsulated by multiwalled carbon nanotubes are studied under hydrostatic pressure (P) via resonance Raman scattering. The LCCs' spectroscopic signature C band ...around 1850 cm^{-1} softens linearly with increasing P. A simple anharmonic force-constant model not only describes such softening but also shows that the LCCs' Young's modulus (E), Grüneisen parameter (γ), and strain (ϵ) follow universal P^{-1} and P^{2} laws, respectively. In particular, γ also presents a unified behavior for all LCCs. To the best of our knowledge, these are the first results reported on such isolated systems and the first work to explore universal P-dependent responses for LCCs' E, ϵ, and γ.
Summary
Glioblastoma (GBM) is an aggressive cancer with a very poor prognosis. Generally viewed as weakly immunogenic, GBM responds poorly to current immunotherapies. To understand this problem more ...clearly we used a combination of natural killer (NK) cell functional assays together with gene and protein expression profiling to define the NK cell response to GBM and explore immunosuppression in the GBM microenvironment. In addition, we used transcriptome data from patient cohorts to classify GBM according to immunological profiles. We show that glioma stem‐like cells, a source of post‐treatment tumour recurrence, express multiple immunomodulatory cell surface molecules and are targeted in preference to normal neural progenitor cells by natural killer (NK) cells ex vivo. In contrast, GBM‐infiltrating NK cells express reduced levels of activation receptors within the tumour microenvironment, with hallmarks of transforming growth factor (TGF)‐β‐mediated inhibition. This NK cell inhibition is accompanied by expression of multiple immune checkpoint molecules on T cells. Single‐cell transcriptomics demonstrated that both tumour and haematopoietic‐derived cells in GBM express multiple, diverse mediators of immune evasion. Despite this, immunome analysis across a patient cohort identifies a spectrum of immunological activity in GBM, with active immunity marked by co‐expression of immune effector molecules and feedback inhibitory mechanisms. Our data show that GBM is recognized by the immune system but that anti‐tumour immunity is restrained by multiple immunosuppressive pathways, some of which operate in the healthy brain. The presence of immune activity in a subset of patients suggests that these patients will more probably benefit from combination immunotherapies directed against multiple immunosuppressive pathways.
Our manuscript challenges the current paradigm that Glioblastoma (GBM) is a poor candidate for immunotherapy, therefore impacting on clinical approaches. We identify NK cells as a target for immunosuppression in GBM, with multiple suppressive pathways within GBM human tumours. We also identify a group of GBM patients with higher immunological activity, who will benefit from immunotherapies that target these immunosuppressive pathways.
The 260-million-year-old Emeishan volcanic province of southwest China overlies and is interbedded with Middle Permian carbonates that contain a record of the Guadalupian mass extinction. Sections in ...the region thus provide an opportunity to directly monitor the relative timing of extinction and volcanism within the same locations. These show that the onset of volcanism was marked by both large phreatomagmatic eruptions and extinctions amongst fusulinacean foraminifers and calcareous algae. The temporal coincidence of these two phenomena supports the idea of a cause-and-effect relationship. The crisis predates the onset of a major negative carbon isotope excursion that points to subsequent severe disturbance of the ocean-atmosphere carbon cycle.
Photodynamic antimicrobial chemotherapy (PACT) combines light, a light-absorbing molecule that initiates a photochemical or photophysical reaction, and oxygen. The combined action of these three ...components originates reactive oxygen species that lead to microorganisms' destruction. The aim was to evaluate the efficiency of PACT on Vibrio fischeri: 1) with buffer solution, varying temperature, pH, salinity and oxygen concentration values; 2) with aquaculture water, to reproduce photoinactivation (PI) conditions in situ.
To monitor the PI kinetics, the bioluminescence of V. fischeri was measured during the experiments. A tricationic meso-substituted porphyrin (Tri-Py(+)-Me-PF) was used as photosensitizer (5 µM in the studies with buffer solution and 10-50 µM in the studies with aquaculture water); artificial white light (4 mW cm(-2)) and solar irradiation (40 mW cm(-2)) were used as light sources; and the bacterial concentration used for all experiments was ≈10(7) CFU mL(-1) (corresponding to a bioluminescence level of 10(5) relative light units--RLU). The variations in pH (6.5-8.5), temperature (10-25°C), salinity (20-40 g L(-1)) and oxygen concentration did not significantly affect the PI of V. fischeri, once in all tested conditions the bioluminescent signal decreased to the detection limit of the method (≈7 log reduction). The assays using aquaculture water showed that the efficiency of the process is affected by the suspended matter. Total PI of V. fischeri in aquaculture water was achieved under solar light in the presence of 20 µM of Tri-Py(+)-Me-PF.
If PACT is to be used in environmental applications, the matrix containing target microbial communities should be previously characterized in order to establish an efficient protocol having into account the photosensitizer concentration, the light source and the total light dose delivered. The possibility of using solar light in PACT to treat aquaculture water makes this technology cost-effective and attractive.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Antimicrobial photodynamic therapy (aPDT) has emerged in the clinical field as a potential alternative to antibiotics to treat microbial infections. No cases of microbial viability recovery or any ...resistance mechanisms against it are yet known. 5,10,15-tris(1-Methylpyridinium-4-yl)-20-(pentafluorophenyl)-porphyrin triiodide (Tri-Py(+)-Me-PF) was used as photosensitizer. Vibrio fischeri and recombinant Escherichia coli were the studied bacteria. To determine the bacterial recovery after treatment, Tri-Py(+)-Me-PF (5.0 microM) was added to bacterial suspensions and the samples were irradiated with white light (40 W m(-2)) for 270 minutes. Then, the samples were protected from light, aliquots collected at different intervals and the bioluminescence measured. To assess the development of resistance after treatment, bacterial suspensions were exposed to white light (25 minutes), in presence of 5.0 microM of Tri-Py(+)-Me-PF (99.99% of inactivation) and plated. After the first irradiation period, surviving colonies were collected from the plate and resuspended in PBS. Then, an identical protocol was used and repeated ten times for each bacterium. The results suggest that aPDT using Tri-Py(+)-Me-PF represents a promising approach to efficiently destroy bacteria since after a single treatment these microorganisms do not recover their viability and after ten generations of partially photosensitized cells neither of the bacteria develop resistance to the photodynamic process.
Crop yields are significantly reduced by aluminum toxicity on highly acidic soils, which comprise up to 50% of the world's arable land. Candidate aluminum tolerance proteins include organic acid ...efflux transporters, with the organic acids forming non-toxic complexes with rhizosphere aluminum. In this study, we used positional cloning to identify the gene encoding a member of the multidrug and toxic compound extrusion (MATE) family, an aluminum-activated citrate transporter, as responsible for the major sorghum (Sorghum bicolor) aluminum tolerance locus, AltSB. Polymorphisms in regulatory regions of AltSB are likely to contribute to large allelic effects, acting to increase AltSB expression in the root apex of tolerant genotypes. Furthermore, aluminum-inducible AltSB expression is associated with induction of aluminum tolerance via enhanced root citrate exudation. These findings will allow us to identify superior AltSB haplotypes that can be incorporated via molecular breeding and biotechnology into acid soil breeding programs, thus helping to increase crop yields in developing countries where acidic soils predominate.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary These guidelines for the management of cutaneous melanoma present an evidence-based guidance for treatment, with identification of the strength of evidence available at the time of ...preparation of the guidelines, and a brief overview of epidemiology, diagnosis, investigation, and follow-up.
► Tri-Py
+-Me-PF effectively photoinactivate T4-like phages. ► Phages after aPDT do not recover their viability and do not develop resistance after 10 successive treatments.
Nowadays, the emergence ...of drug resistant microorganisms is a public health concern. The antimicrobial photodynamic therapy (aPDT) has an efficient action against a wide range of microorganisms and can be viewed as an alternative approach for treating microbial infections. The aim of this study was to determine if a model target virus (T4-like bacteriophage), in the presence of the tricationic porphyrin 5,10,15-tris(1-methylpyridinium-4-yl)-20-(pentafluorophenyl)porphyrin tri-iodide (Tri-Py
+-Me-PF), can develop resistance to aPDT and recover its viability after photodynamic treatments. To assess the development of aPDT resistance after repeated treatments, a suspension of T4-like bacteriophage was irradiated with white light (40
W
m
−2) for 120
min in the presence of 5.0
μM of Tri-Py
+-Me-PF (99.99% of inactivation) and new phage suspensions were produced from the surviving phages, after each cycle of light exposure. The procedure was repeated ten times. To evaluate the recovery of viral viability after photoinactivation, a suspension of T4-like bacteriophage was irradiated with white light for 120
min in the presence of 5.0
μM of Tri-Py
+-Me-PF on five consecutive days. In each day, an aliquot of the irradiated suspension was plated and the number of lysis plaques was counted after 24, 48, 72, 96 and 120
h of dark incubation at 37
°C. The profile of bacteriophage photoinactivation did not change after ten consecutive cycles and no recovery of viability was detected after five accumulated cycles of photodynamic treatment. The results suggest that aPDT represents a valuable and promising alternative therapy to treat viral infections, overcoming the problem of microbial resistance.