A classical inflation-eruption-deflation cycle of a volcano is useful to conceptualize the time-evolving deformation of volcanic systems. Such a model predicts accelerated uplift during pre-eruptive ...periods, followed by subsidence during the co-eruptive stage. Some volcanoes show puzzling persistent uplift signals with minor or no other geophysical or geochemical variations, which are difficult to interpret. Such temporal behaviors are usually observed in large calderas (e.g., Yellowstone, Long Valley, Campi Flegrei, Rabaul), but less commonly for stratovolcanoes. Volcano deformation needs to be better understood during inter-eruptive stages, to assess its value as a tool for forecasting eruptions and to understand the processes governing the unrest behavior. Here, we analyze inter-eruptive uplift signals at Three Sisters, a complex stratovolcano in Oregon (United States), which in recent decades shows persistent inter-eruptive uplift signals without associated eruptive activity. Using a Bayesian inversion method, we re-assessed the source characteristics (magmatic system geometry and location) and its uncertainties. Furthermore, we evaluate the most recent evolution of the surface deformation signals combining both GPS and InSAR data through a new non-subjective linear regularization inversion procedure to estimate the 26 years-long time-series. Our results constrain the onset of the Three Sisters volcano inflation to be between October 1998 and August 1999. In the absence of new magmatic inputs, we estimate a continuous uplift signal, at diminishing but detectable rates, to last for few decades. The observed uplift decay observed at Three Sisters is consistent with a viscoelastic response of the crust, with viscosity of ∼10
18
Pa s around a magmatic source with a pressure change which increases in finite time to a constant value. Finally, we compare Three Sisters volcano time series with historical uplift at different volcanic systems. Proper modeling of scaled inflation time series indicates a unique and well-defined exponential decay in temporal behavior. Such evidence supports that this common temporal evolution of uplift rates could be a potential indicator of a rather reduced set of physical processes behind inter-eruptive uplift signals.
Pediatric brain tumors, including medulloblastoma (MB), represent a significant challenge in clinical oncology. Early diagnosis, accurate monitoring of therapeutic response, and the detection of ...minimal residual disease (MRD) are crucial for improving outcomes in these patients. This review aims to explore recent advancements in liquid biopsy techniques for monitoring pediatric brain tumors, with a specific focus on medulloblastoma. The primary research question is how liquid biopsy techniques can be effectively utilized for these purposes. Liquid biopsies, particularly the analysis of circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF), are investigated as promising noninvasive tools. This comprehensive review examines the components of liquid biopsies, including ctDNA, cell-free DNA (cfDNA), and microRNA (miRNA). Their applications in diagnosis, prognosis, and MRD assessment are critically assessed. The review also discusses the role of liquid biopsies in categorizing medulloblastoma subgroups, risk stratification, and the identification of therapeutic targets. Liquid biopsies have shown promising applications in the pediatric brain tumor field, particularly in medulloblastoma. They offer noninvasive means of diagnosis, monitoring treatment response, and detecting MRD. These biopsies have played a pivotal role in subgroup classification and risk stratification of medulloblastoma patients, aiding in the identification of therapeutic targets. However, challenges related to sensitivity and specificity are noted. In conclusion, this review highlights the growing importance of liquid biopsies, specifically ctDNA analysis in CSF, in pediatric brain tumor management, with a primary focus on medulloblastoma. Liquid biopsies have the potential to revolutionize patient care by enabling early diagnosis, accurate monitoring, and MRD detection. Nevertheless, further research is essential to validate their clinical utility fully. The evolving landscape of liquid biopsy applications underscores their promise in improving outcomes for pediatric brain tumor patients.
•Internal Market Orientation (IMO) has been empirically tested in hotel sector.•WFB (Work/Family Balance) has been included as a sub-dimension of IMO.•The presence of an IMO improves job satisfaction ...and employee commitment.
The study has three aims. First, to measure internal market orientation second, to analyze the relationships between IMO and two organizational consequences: job satisfaction and commitment; and third, to incorporate a new sub-dimension work/family balance. Empirical research has been done in a sample of Spanish hotels. Results show that IMO is a strategic determinant of both job satisfaction and employee commitment.
An early and accurate diagnosis of multiple sclerosis (MS) is very important, since it allows early treatment initiation, which reduces the activity of the disease. Oligoclonal IgG band (OCGB) ...detection is a good ancillary tool for MS diagnosis. However, it was argued that its usefulness was limited by the high interlaboratory variability. In the last years, different techniques for OCGB detection have appeared. We performed a blinded aleatorized multicenter study in 19 Spanish hospitals to assess the accuracy and reproducibility of OCGB detection in this new scenario. We studied cerebrospinal fluid (CSF) and serum samples from 114 neurological patients. Every hospital contributed to the study with triplicated pairs of CSF and serum samples of six patients and analyzed 18 different samples. Global analysis rendered a sensitivity of 92.1%, a specificity of 95.1% and a Kappa value of 0.81. This shows that current techniques for OCGB detection have good accuracy and a high interlaboratory reproducibility and thus, represent a good tool for MS diagnosis. When we analyzed separately the different techniques used for OCGB detection, the highest concordance was observed in western blot with alkaline phosphatase detection (kappa=0.91). This indicates that high sensitivity techniques improve the reproducibility of this assay.
► We conducted a multicentric study of new methods for oligoclonal band detection. ► We assessed the accuracy of these methods for MS diagnosis. ► They showed high sensitivity, specificity, and reproducibility. ► The use alkaline phosphatase detection showed the highest concordance. ► This method improves the reproducibility of oligoclonal band detection.
The question of how tourist destination image is generated is an issue of significant interest in the tourism management field. The present work analyzes the effect of the design of a tourist ...destination website, and the effect of the tourist's processing of information, on the destination image that the tourist creates. In order to achieve this objective, an experimental design was carried out, in which a destination website was specially created in order to manipulate message type and information-overload. The results demonstrate that destination image is more positive when emotional messages are employed on the website and when the individual does not experience overload. The work also demonstrates the moderating role of involvement, in the effect of the factors manipulated in the study (message type and information-overload) on tourist destination image. The conclusions reached in this study hold some interesting implications for practitioners working in tourist destination management.
•The effect of tourist destination website design on destination image is analyzed.•The destination image is more positive when emotional messages are employed.•The destination image is more positive when the individual does not feel overloaded.•The moderating effect of consumer involvement on message type is demonstrated.•The moderating effect of consumer involvement on overload is demonstrated.
Most eukaryotic messenger RNAs (mRNAs) are processed at their 3' end by the cleavage and polyadenylation specificity factor (CPF/CPSF). CPF mediates the endonucleolytic cleavage of the pre-mRNA and ...addition of a polyadenosine (poly(A)) tail, which together define the 3' end of the mature transcript. The activation of CPF is highly regulated to maintain the fidelity of RNA processing. Here, using cryo-EM of yeast CPF, we show that the Mpe1 subunit directly contacts the polyadenylation signal sequence in nascent pre-mRNA. The region of Mpe1 that contacts RNA also promotes the activation of CPF endonuclease activity and controls polyadenylation. The Cft2 subunit of CPF antagonizes the RNA-stabilized configuration of Mpe1. In vivo, the depletion or mutation of Mpe1 leads to widespread defects in transcription termination by RNA polymerase II, resulting in transcription interference on neighboring genes. Together, our data suggest that Mpe1 plays a major role in accurate 3' end processing, activating CPF, and ensuring timely transcription termination.
The search for voluminous stators that may accommodate large rotator units and speed rotational dynamics in the solid state led us to investigate a simple and efficient method for the synthesis of ...molecular rotors with tert-butyldiphenylsilyl-protected (TBDPS) triphenylmethyl stators. Additionally, solid state characterization of these systems with two-, four-, and six-TBDPS groups provided us with a description of their crystallinity and thermal stability. Among them, molecular rotor 7c with the largest and most symmetric stator resulting from six peripheral silyl groups showed the best tendency to crystallize, and the study of its isotopologue 7c-d 4 by solid state 2H NMR revealed a 2-fold motion of the 1,4-diethynylphenylene-d 4 rotator in the kHz regime.
: Infectious complication represents a significant source of morbidity and mortality in heart transplant recipients. To assess humoral immunity markers that can predict the development of infection, ...38 consecutive recipients of heart transplants performed at a single center were prospectively studied. Induction therapy included daclizumab. Immunoglobulin (IgG, IgA, IgM) and complement factors (C3, C4, and factor B) were performed by nephelometry in peripheral blood samples obtained before transplantation, and 7 days and 1 month after transplantation. During a mean follow‐up of 16.9 months, 13 patients had at least one episode of infection (34.2%). Eight of these were cytomegalovirus (CMV) infections treated with intravenous ganciclovir, 2 were bacterial pneumonia, 1 patient had bacterial septicemia, 1 patient had urinary tract infection, and 1 patient had pulmonary nocardiosis. No significant association was found between infection and age, sex, immunosuppression, CMV serostatus of donor and recipient, or treated rejection episodes. Pre‐transplant IgG (below median value=1140 mg/dL; relative risk RR 3.69; 95% confidence interval CI 1.01–13.54; P=0.04) and post‐transplant IgG levels at day 7 (below median value=679 mg/dL; RR 11.21; CI 1.04–89.48; P=0.022) were associated with an increase in the risk for developing infections. Early monitoring of immunoglobulin levels might help to identify the risk for developing infection in heart transplantation.
Craspase is a CRISPR RNA-guided, RNA-activated protease Hu, Chunyi; van Beljouw, Sam P B; Nam, Ki Hyun ...
Science (American Association for the Advancement of Science),
09/2022, Letnik:
377, Številka:
6612
Journal Article
Recenzirano
Odprti dostop
The CRISPR-Cas type III-E RNA-targeting effector complex gRAMP/Cas7-11 is associated with a caspase-like protein (TPR-CHAT/Csx29) to form Craspase (CRISPR-guided caspase). Here, we use cryo-electron ...microscopy snapshots of Craspase to explain its target RNA cleavage and protease activation mechanisms. Target-guide pairing extending into the 5' region of the guide RNA displaces a gating loop in gRAMP, which triggers an extensive conformational relay that allosterically aligns the protease catalytic dyad and opens an amino acid side-chain-binding pocket. We further define Csx30 as the endogenous protein substrate that is site-specifically proteolyzed by RNA-activated Craspase. This protease activity is switched off by target RNA cleavage by gRAMP and is not activated by RNA targets containing a matching protospacer flanking sequence. We thus conclude that Craspase is a target RNA-activated protease with self-regulatory capacity.
Type III CRISPR-Cas immunity is widespread in prokaryotes and is generally mediated by multisubunit effector complexes. These complexes recognize complementary viral transcripts and can activate ...ancillary immune proteins. Here, we describe a type III-E effector from
“Scalindua brodae” (
-gRAMP), which is natively encoded by a single gene with several type III domains fused together. This effector uses CRISPR RNA to guide target RNA recognition and cleaves single-stranded RNA at two defined positions six nucleotides apart.
-gRAMP physically combines with the caspase-like TPR-CHAT peptidase to form the CRISPR-guided caspase (Craspase) complex, suggesting a potential mechanism of target RNA–induced protease activity to gain viral immunity.
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