4,648 research outputs found
Novel Biomarkers in Sinonasal Cancers: from Bench to Bedside
Purpose of Review: Sinonasal cancers are a heterogenous group of rare cancers for which histopathological diagnosis can be very challenging and treatment options are limited for advanced disease in particular. Here, we review the candidacy of novel diagnostic and prognostic biomarkers, and therapeutic targets for sinonasal cancers. / Recent Findings: Molecular multidimensional analyses of sinonasal cancers have been lagging behind other major cancers, but there are numerous publications describing the discovery of novel candidate biomarkers, e.g. the methylation classifier, originally developed for brain cancers, and gene expression panels for the prediction of response to induction chemotherapy in sinonasal undifferentiated carcinoma. The most promising biomarkers are summarized and discussed further with regard to their clinical applicability and future potential. /Summary: Many of the described novel biomarkers for sinonasal cancers will eventually overcome the pitfalls associated with the frequently non-specific immunohistological tests. With comprehensive, multidimensional molecular testing of these tumours in collaborative consortia projects, our better understanding of the molecular mechanisms of sinonasal cancers and their carcinogenesis will determine the most useful diagnostic and prognostic biomarkers, allow stringent multi-institutional validation and guide trials on targeted therapies
Whole-Body Barometric Plethysmography Characterizes Upper Airway Obstruction in 3 Brachycephalic Breeds of Dogs.
BACKGROUND: A novel test using whole-body barometric plethysmography (WBBP) was developed recently to diagnose brachycephalic obstructive airway syndrome (BOAS) in unsedated French bulldogs. HYPOTHESIS/OBJECTIVES: The hypotheses of this study were: (1) respiratory characteristics are different between healthy nonbrachycephalic dogs and brachycephalic dogs; and among pugs, French bulldogs, and bulldogs; and (2) obesity and stenotic nares are risk factors for BOAS. The main objective was to establish a diagnostic test for BOAS in these 3 breeds. ANIMALS: A total of 266 brachycephalic dogs (100 pugs, 100 French bulldogs, and 66 bulldogs) and 28 nonbrachycephalic dogs. METHODS: Prospective study. Exercise tolerance tests with respiratory functional grading, and WBBP were performed on all dogs. Data from WBBP were associated with functional grades to train quadratic discriminant analysis tools to assign dogs to BOAS+ and BOAS- groups. A BOAS index (0-100%) was calculated for each dog. Receiver operating characteristic (ROC) curves were used to evaluate classification ability. RESULTS: Minute volume was decreased significantly in asymptomatic pugs (P = .009), French bulldogs (P = .026), and bulldogs (P < .0001) when compared to nonbrachycephalic controls. Respiratory characteristics were different among breeds and affected dogs had a significant increase in trace variation. The BOAS index predicted BOAS status for each breed with 94-97% (95% confidence interval [CI], 88.9-100%) accuracy (area under the ROC curve). Both obesity (P = .04) and stenotic nares (P = .004) were significantly associated with BOAS. CONCLUSIONS AND CLINICAL IMPORTANCE: The WBBP can be used as a clinical tool to diagnose BOAS noninvasively and objectively.This study is supported by a grant from the Kennel Club Charitable Trust (KCCT), no. RG71960.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/jvim.1393
The carbon cycle in Mexico: past, present and future of C stocks and fluxes
PublishedThe Supplement related to this article is available online
at doi:10.5194/bg-13-223-2016-supplement.We modeled the carbon (C) cycle in Mexico with a process-based approach. We used different available products (satellite data, field measurements, models and flux towers) to estimate C stocks and fluxes in the country at three different time frames: present (defined as the period 2000–2005), the past century (1901–2000) and the remainder of this century (2010–2100). Our estimate of the gross primary productivity (GPP) for the country was 2137 ± 1023 TgC yr−1 and a total C stock of 34 506 ± 7483 TgC, with 20 347 ± 4622 TgC in vegetation and 14 159 ± 3861 in the soil.
Contrary to other current estimates for recent decades, our results showed that Mexico was a C sink over the period 1990–2009 (+31 TgC yr−1) and that C accumulation over the last century amounted to 1210 ± 1040 TgC. We attributed this sink to the CO2 fertilization effect on GPP, which led to an increase of 3408 ± 1060 TgC, while both climate and land use reduced the country C stocks by −458 ± 1001 and −1740 ± 878 TgC, respectively. Under different future scenarios, the C sink will likely continue over the 21st century, with decreasing C uptake as the climate forcing becomes more extreme. Our work provides valuable insights on relevant driving processes of the C cycle such as the role of drought in drylands (e.g., grasslands and shrublands) and the impact of climate change on the mean residence time of soil C in tropical ecosystems.The lead author (G. Murray-Tortarolo) thanks
CONACYT-CECTI, the University of Exeter and Secretaría de
Educación Pública (SEP) for their funding of this project. The
authors extend their thanks to Carlos Ortiz Solorio and to the
Colegio de Posgraduados for the field soil data and to the Alianza
Redd+ Mexico for the field biomass data. This project would not
have been possible without the valuable data from the CMIP5
models. A. Arneth, G. Murray-Tortarolo, A. Wiltshire and S. Sitch
acknowledge the support of the European Commission-funded
project LULCC4C (grant no. 603542). A. Wiltshire was partsupported
by the Joint UK DECC/Defra Met Office Hadley Centre
Climate Programme (GA01101)
Respiratory viral infections in exacerbation of chronic airway inflammatory diseases: novel mechanisms and insights from the upper airway epithelium.
Respiratory virus infection is one of the major sources of exacerbation of chronic airway inflammatory diseases. These exacerbations are associated with high morbidity and even mortality worldwide. The current understanding on viral-induced exacerbations is that viral infection increases airway inflammation which aggravates disease symptoms. Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models have evoked new understandings as to the mechanisms of viral exacerbations. In this review, we will focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. First, we reviewed the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases. Subsequently we also summarized how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations. Further we highlighted the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection. This review consolidates the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases
Pretreatment with a novel aquaporin 4 inhibitor, TGN-020, significantly reduces ischemic cerebral edema
We investigated the in vivo effects of a novel aquaporin 4 (AQP4) inhibitor 2-(nicotinamide)-1,3,4-thiadiazole, TGN-020, in a mouse model of focal cerebral ischemia using 7.0-T magnetic resonance imaging (MRI). Pretreatment with TGN-020 significantly reduced brain edema associated with brain ischemia, as reflected by percentage of brain swelling volume (%BSV), 12.1 ± 6.3% in the treated group, compared to (20.8 ± 5.9%) in the control group (p < 0.05), and in the size of cortical infarction as reflected by the percentage of hemispheric lesion volume (%HLV), 20.0 ± 7.6% in the treated group, compared to 30.0 ± 9.1% in the control group (p < 0.05). The study indicated the potential pharmacological use of AQP4 inhibition in reducing brain edema associated with focal ischemia
Outlier Edge Detection Using Random Graph Generation Models and Applications
Outliers are samples that are generated by different mechanisms from other
normal data samples. Graphs, in particular social network graphs, may contain
nodes and edges that are made by scammers, malicious programs or mistakenly by
normal users. Detecting outlier nodes and edges is important for data mining
and graph analytics. However, previous research in the field has merely focused
on detecting outlier nodes. In this article, we study the properties of edges
and propose outlier edge detection algorithms using two random graph generation
models. We found that the edge-ego-network, which can be defined as the induced
graph that contains two end nodes of an edge, their neighboring nodes and the
edges that link these nodes, contains critical information to detect outlier
edges. We evaluated the proposed algorithms by injecting outlier edges into
some real-world graph data. Experiment results show that the proposed
algorithms can effectively detect outlier edges. In particular, the algorithm
based on the Preferential Attachment Random Graph Generation model consistently
gives good performance regardless of the test graph data. Further more, the
proposed algorithms are not limited in the area of outlier edge detection. We
demonstrate three different applications that benefit from the proposed
algorithms: 1) a preprocessing tool that improves the performance of graph
clustering algorithms; 2) an outlier node detection algorithm; and 3) a novel
noisy data clustering algorithm. These applications show the great potential of
the proposed outlier edge detection techniques.Comment: 14 pages, 5 figures, journal pape
Early growth response gene-2 (Egr-2) regulates the development of B and T cells
The study was supported by Arthritis Research UK.
Copyright @ 2011 Li et al.BACKGROUND: Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development. METHODS AND FINDINGS: The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2+ lymphocytes resulted in a severe reduction of CD4+CD8+ (DP) cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP) T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow. CONCLUSIONS: Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.This article is provided by the Brunel Open Access publishing fund
Ultrathin 2 nm gold as ideal impedance-matched absorber for infrared light
Thermal detectors are a cornerstone of infrared (IR) and terahertz (THz)
technology due to their broad spectral range. These detectors call for suitable
broad spectral absorbers with minimalthermal mass. Often this is realized by
plasmonic absorbers, which ensure a high absorptivity butonly for a narrow
spectral band. Alternativly, a common approach is based on impedance-matching
the sheet resistance of a thin metallic film to half the free-space impedance.
Thereby, it is possible to achieve a wavelength-independent absorptivity of up
to 50 %, depending on the dielectric properties of the underlying substrate.
However, existing absorber films typicallyrequire a thickness of the order of
tens of nanometers, such as titanium nitride (14 nm), whichcan significantly
deteriorate the response of a thermal transducers. Here, we present the
application of ultrathin gold (2 nm) on top of a 1.2 nm copper oxide seed layer
as an effective IR absorber. An almost wavelength-independent and long-time
stable absorptivity of 47(3) %, ranging from 2 m to 20 m, could be
obtained and is further discussed. The presented gold thin-film represents
analmost ideal impedance-matched IR absorber that allows a significant
improvement of state-of-the-art thermal detector technology
Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism
The Autism Genome Project has assembled two large datasets originally designed for linkage analysis and genome-wide association analysis, respectively: 1,069 multiplex families genotyped on the Affymetrix 10 K platform, and 1,129 autism trios genotyped on the Illumina 1 M platform. We set out to exploit this unique pair of resources by analyzing the combined data with a novel statistical method, based on the PPL statistical framework, simultaneously searching for linkage and association to loci involved in autism spectrum disorders (ASD). Our analysis also allowed for potential differences in genetic architecture for ASD in the presence or absence of lower IQ, an important clinical indicator of ASD subtypes. We found strong evidence of multiple linked loci; however, association evidence implicating specific genes was low even under the linkage peaks. Distinct loci were found in the lower IQ families, and these families showed stronger and more numerous linkage peaks, while the normal IQ group yielded the strongest association evidence. It appears that presence/absence of lower IQ (LIQ) demarcates more genetically homogeneous subgroups of ASD patients, with not just different sets of loci acting in the two groups, but possibly distinct genetic architecture between them, such that the LIQ group involves more major gene effects (amenable to linkage mapping), while the normal IQ group potentially involves more common alleles with lower penetrances. The possibility of distinct genetic architecture across subtypes of ASD has implications for further research and perhaps for research approaches to other complex disorders as well
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