3,152 research outputs found
A Novel Nanoproteomic Approach for the Identification of Molecular Targets Associated with Thyroid Tumors
A thyroid nodule is the most common presentation of thyroid cancer; thus, it is extremely important to differentiate benign from malignant nodules. Within malignant lesions, classification of a thyroid tumor is the primary step in the assessment of the prognosis and selection of treatment. Currently, fine-needle aspiration biopsy (FNAB) is the preoperative test most commonly used for the initial thyroid nodule diagnosis. However, due to some limitations of FNAB, different high-throughput âomicsâ approaches have emerged that could further support diagnosis based on histopathological patterns. In the present work, formalin-fixed paraffin-embedded (FFPE) tissue specimens from normal (non-neoplastic) thyroid (normal controls (NCs)), benign tumors (follicular thyroid adenomas (FTAs)), and some common types of well-differentiated thyroid carcinoma (follicular thyroid carcinomas (FTCs), conventional or classical papillary thyroid carcinomas (CV-PTCs), and the follicular variant of papillary thyroid carcinomas (FV-PTCs)) were analyzed. For the first time, FFPE thyroid samples were deparaffinized using an easy, fast, and non-toxic method. Protein extracts from thyroid tissue samples were analyzed using a nanoparticle-assisted proteomics approach combined with shotgun LC-MS/MS. The differentially regulated proteins found to be specific for the FTA, FTC, CV-PTC, and FV-PTC subtypes were analyzed with the bioinformatic tools STRING and PANTHER showing a profile of proteins implicated in the thyroid cancer metabolic reprogramming, cancer progression, and metastasis. These proteins represent a new source of potential molecular targets related to thyroid tumorsThis work was supported by grants from the Instituto de Salud Carlos III (ISCIII), State Research Agency (AEI), and Ministry of Science and Innovation (Spain), with the participation of European FEDER funds, to C.N. (CP16/00139) and J.M.C.-T. (PI19/01316)S
European Mixed Forests: definition and research perspectives
peer-reviewedAim of study: We aim at (i) developing a reference definition of mixed forests in order to harmonize comparative research in mixed forests and (ii) briefly review the research perspectives in mixed forests.
Area of study: The definition is developed in Europe but can be tested worldwide.
Material and methods: Review of existent definitions of mixed forests based and literature review encompassing
dynamics, management and economic valuation of mixed forests.
Main results: A mixed forest is defined as a forest unit, excluding linear formations, where at least two tree species coexist at any developmental stage, sharing common resources (light, water, and/or soil nutrients). The presence of each of the component species is normally quantified as a proportion of the number of stems or of basal area, although volume, biomass or canopy cover as well as proportions by occupied stand area may be used for specific objectives. A variety of structures and patterns of mixtures can occur, and the interactions between the component species and their relative proportions may change over time. The research perspectives identified are (i) species interactions and responses to hazards, (ii) the concept of maximum density in mixed forests, (iii) conversion of monocultures to mixed-species forest and (iv) economic valuation of ecosystem services provided by mixed forests.
Research highlights: The definition is considered a high-level one which encompasses previous attempts to define mixed forests. Current fields of research indicate that gradient studies, experimental design approaches, and model simulations are key topics providing new research opportunities.The networking in this study has been supported by COST Action FP1206 EuMIXFOR
Research-based flow cytometry assays for pathogenic assessment in the human B-cell biology of gene variants revealed in the diagnosis of inborn errors of immunity: a Brutonâs tyrosine kinase case-study
IntroductionInborn errors of immunity (IEI) are an expanding group of rare diseases whose field has been boosted by next-generation sequencing (NGS), revealing several new entities, accelerating routine diagnoses, expanding the number of atypical presentations and generating uncertainties regarding the pathogenic relevance of several novel variants.MethodsResearch laboratories that diagnose and provide support for IEI require accurate, reproducible and sustainable phenotypic, cellular and molecular functional assays to explore the pathogenic consequences of human leukocyte gene variants and contribute to their assessment. We have implemented a set of advanced flow cytometry-based assays to better dissect human B-cell biology in a translational research laboratory. We illustrate the utility of these techniques for the in-depth characterization of a novel (c.1685G>A, p.R562Q) de novo gene variant predicted as probably pathogenic but with no previous insights into the protein and cellular effects, located in the tyrosine kinase domain of the Brutonâs tyrosine kinase (BTK) gene, in an apparently healthy 14-year-old male patient referred to our clinic for an incidental finding of low immunoglobulin (Ig) M levels with no history of recurrent infections.Results and discussionA phenotypic analysis of bone marrow (BM) revealed a slightly high percentage of pre-B-I subset in BM, with no blockage at this stage, as typically observed in classical X-linked agammaglobulinemia (XLA) patients. The phenotypic analysis in peripheral blood also revealed reduced absolute numbers of B cells, all pre-germinal center maturation stages, together with reduced but detectable numbers of different memory and plasma cell isotypes. The R562Q variant allows Btk expression and normal activation of anti-IgM-induced phosphorylation of Y551 but diminished autophosphorylation at Y223 after anti IgM and CXCL12 stimulation. Lastly, we explored the potential impact of the variant protein for downstream Btk signaling in B cells. Within the canonical nuclear factor kappa B (NF-ÎșB) activation pathway, normal IÎșBα degradation occurs after CD40L stimulation in patient and control cells. In contrast, disturbed IÎșBα degradation and reduced calcium ion (Ca2+) influx occurs on anti-IgM stimulation in the patientâs B cells, suggesting an enzymatic impairment of the mutated tyrosine kinase domain
Highlights from the Pierre Auger Observatory
The Pierre Auger Observatory is the world's largest cosmic ray observatory.
Our current exposure reaches nearly 40,000 km str and provides us with an
unprecedented quality data set. The performance and stability of the detectors
and their enhancements are described. Data analyses have led to a number of
major breakthroughs. Among these we discuss the energy spectrum and the
searches for large-scale anisotropies. We present analyses of our X
data and show how it can be interpreted in terms of mass composition. We also
describe some new analyses that extract mass sensitive parameters from the 100%
duty cycle SD data. A coherent interpretation of all these recent results opens
new directions. The consequences regarding the cosmic ray composition and the
properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray
Conference, Rio de Janeiro 201
A search for point sources of EeV photons
Measurements of air showers made using the hybrid technique developed with
the fluorescence and surface detectors of the Pierre Auger Observatory allow a
sensitive search for point sources of EeV photons anywhere in the exposed sky.
A multivariate analysis reduces the background of hadronic cosmic rays. The
search is sensitive to a declination band from -85{\deg} to +20{\deg}, in an
energy range from 10^17.3 eV to 10^18.5 eV. No photon point source has been
detected. An upper limit on the photon flux has been derived for every
direction. The mean value of the energy flux limit that results from this,
assuming a photon spectral index of -2, is 0.06 eV cm^-2 s^-1, and no celestial
direction exceeds 0.25 eV cm^-2 s^-1. These upper limits constrain scenarios in
which EeV cosmic ray protons are emitted by non-transient sources in the
Galaxy.Comment: 28 pages, 10 figures, accepted for publication in The Astrophysical
Journa
Reconstruction of inclined air showers detected with the Pierre Auger Observatory
We describe the method devised to reconstruct inclined cosmic-ray air showers
with zenith angles greater than detected with the surface array of
the Pierre Auger Observatory. The measured signals at the ground level are
fitted to muon density distributions predicted with atmospheric cascade models
to obtain the relative shower size as an overall normalization parameter. The
method is evaluated using simulated showers to test its performance. The energy
of the cosmic rays is calibrated using a sub-sample of events reconstructed
with both the fluorescence and surface array techniques. The reconstruction
method described here provides the basis of complementary analyses including an
independent measurement of the energy spectrum of ultra-high energy cosmic rays
using very inclined events collected by the Pierre Auger Observatory.Comment: 27 pages, 19 figures, accepted for publication in Journal of
Cosmology and Astroparticle Physics (JCAP
Operations of and Future Plans for the Pierre Auger Observatory
Technical reports on operations and features of the Pierre Auger Observatory,
including ongoing and planned enhancements and the status of the future
northern hemisphere portion of the Observatory. Contributions to the 31st
International Cosmic Ray Conference, Lodz, Poland, July 2009.Comment: Contributions to the 31st ICRC, Lodz, Poland, July 200
The Pierre Auger Observatory III: Other Astrophysical Observations
Astrophysical observations of ultra-high-energy cosmic rays with the Pierre
Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference,
Beijing, China, August 201
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