318 research outputs found
Latin American Collaborative Research on Aplastic Anemia (LARAA): creating a regional registry
Aplastic anemia (AA) is a rare but serious disease that affects hematopoietic stem cells and is characterized by pancytopenia and a hypocellular bone marrow. It can be a hereditary or acquired condition. Acquired AA has an incidence of 2 per million per year in Europe, but the incidence is two to three times higher in Asia. In Latin America, there is little epidemiologic data on this disease. The most important treatments for AA are bone marrow transplantation and immunosuppressive treatment with antithymocyte globulin and cyclosporine. But access to these treatments is restricted in some areas of Latin America.
At the American Society of Hematology (ASH) Annual Meeting in 2016, representatives of the Hematology Societies of Latin America, with the support of the ASH International Program, met to discuss possible collaborative efforts. Everyone agreed that lack of reliable information is one of the main barriers to designing significant clinical trials for the region; therefore, starting a registry of hematologic diseases for the region has become a main goal of the group. In April 2017, at the ASH Highlights meeting in Latin America, AA was selected as the first disease that would be used to begin the collaborative action. National hematology societies of Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Paraguay, Peru, Uruguay, and Venezuela have made a commitment to help develop the Latin American Registry for Aplastic Anemia (LARAA)
Random graphs with arbitrary degree distributions and their applications
Recent work on the structure of social networks and the internet has focussed
attention on graphs with distributions of vertex degree that are significantly
different from the Poisson degree distributions that have been widely studied
in the past. In this paper we develop in detail the theory of random graphs
with arbitrary degree distributions. In addition to simple undirected,
unipartite graphs, we examine the properties of directed and bipartite graphs.
Among other results, we derive exact expressions for the position of the phase
transition at which a giant component first forms, the mean component size, the
size of the giant component if there is one, the mean number of vertices a
certain distance away from a randomly chosen vertex, and the average
vertex-vertex distance within a graph. We apply our theory to some real-world
graphs, including the world-wide web and collaboration graphs of scientists and
Fortune 1000 company directors. We demonstrate that in some cases random graphs
with appropriate distributions of vertex degree predict with surprising
accuracy the behavior of the real world, while in others there is a measurable
discrepancy between theory and reality, perhaps indicating the presence of
additional social structure in the network that is not captured by the random
graph.Comment: 19 pages, 11 figures, some new material added in this version along
with minor updates and correction
Identification and relative quantification of tyrosine nitration in a model peptide using two-dimensional infrared spectroscopy
Nitration of tyrosine in proteins and peptides is a post-translational modification that occurs under conditions of oxidative stress. It is implicated in a variety of medical conditions, including neurodegenerative and cardiovascular diseases. However, monitoring tyrosine nitration and understanding its role in modifying biological function remains a major challenge. In this work, we investigate the use of electron-vibration-vibration (EVV) two-dimensional infrared (2DIR) spectroscopy for the study of tyrosine nitration in model peptides. We demonstrate the ability of EVV 2DIR spectroscopy to differentiate between the neutral and deprotonated states of 3-nitrotyrosine, and we characterize their spectral signatures using information obtained from quantum chemistry calculations and simulated EVV 2DIR spectra. To test the sensitivity of the technique, we use mixed-peptide samples containing various levels of tyrosine nitration, and we use mass spectrometry to independently verify the level of nitration. We conclude that EVV 2DIR spectroscopy is able to provide detailed spectroscopic information on peptide side-chain modifications and to detect nitration levels down to 1%. We further propose that lower nitration levels could be detected by introducing a resonant Raman probe step to increase the detection sensitivity of EVV 2DIR spectroscopy. (Graph Presented)
An exceptionally well-preserved skeleton of Palaeothentes from the Early Miocene of Patagonia, Argentina: new insights into the anatomy of extinct paucituberculatan marsupials
International audienc
The genome sequencing of an albino Western lowland gorilla reveals inbreeding in the wild
Background The only known albino gorilla, named Snowflake, was a male wild born individual from Equatorial Guinea who lived at the Barcelona Zoo for almost 40 years. He was diagnosed with non-syndromic oculocutaneous albinism, i.e. white hair, light eyes, pink skin, photophobia and reduced visual acuity. Despite previous efforts to explain the genetic cause, this is still unknown. Here, we study the genetic cause of his albinism and making use of whole genome sequencing data we find a higher inbreeding coefficient compared to other gorillas. Results We successfully identified the causal genetic variant for Snowflake¿s albinism, a non-synonymous single nucleotide variant located in a transmembrane region of SLC45A2. This transporter is known to be involved in oculocutaneous albinism type 4 (OCA4) in humans. We provide experimental evidence that shows that this amino acid replacement alters the membrane spanning capability of this transmembrane region. Finally, we provide a comprehensive study of genome-wide patterns of autozygogosity revealing that Snowflake¿s parents were related, being this the first report of inbreeding in a wild born Western lowland gorilla. Conclusions In this study we demonstrate how the use of whole genome sequencing can be extended to link genotype and phenotype in non-model organisms and it can be a powerful tool in conservation genetics (e.g., inbreeding and genetic diversity) with the expected decrease in sequencing cost. Keywords: Gorilla; Albinism; Inbreeding; Genome; Conservatio
Raman Scattering in the Inorganic Spin-Peierls System alpha'-Na_{1-delta}V_2O_5
We have studied the spin-Peierls (SP) transition in alpha'-Na_{1-delta}V_2O_5
(delta = 0, 0.01 and 0.1) by means of Raman scattering. At room temperature, we
observe six A_1 and three A_2 phonon modes and a broad Raman band. Below
T_{SP}several new peaks and a new broad band appear. The new peak at 62 cm^{-1}
originates from the SP-gap excitation. The new peak at 128 cm^{-1} and the new
broad band between 130 and 400 cm^{-1} come from two magnetic excitations. The
new peaks at 102, 646 and 944 cm^{-1} are assigned to the folded phonon modes
and their Na^+-ion deficiency dependence shows that the defect of Na^+ ion
suppresses the SPtransition. The polarized Raman spectra below T_{SP} suggest
that the possible crystal symmetry is C_s^2(Pn) or C_1^1(P1). The asymmetric
lineshape of the 531-cm^{-1} peak superimposed on the electronic Raman band
from the d-d transition around 600 cm^{-1} is interpreted in terms of the Fano
resonance between the electronic continuous band and the phonon with a finite
lifetime. The defects of the Na^+ ions reduce the Fano effect because the life
time of the phonon and the phonon-continuum interaction are decreased.Comment: 24 pages, 10 Postscript figures,uses jpsj.sty and epsf.sty. in press
in J. Phys. Soc. Jp
Eruptive papules during efalizumab (anti-CD11a) therapy of psoriasis vulgaris: a case series
BACKGROUND: Newer biological therapies for moderate-to-severe psoriasis are being used more frequently, but unexpected effects may occur. CASE PRESENTATIONS: We present a group of 15 patients who developed inflammatory papules while on efalizumab therapy (Raptiva, Genentech Inc, anti-CD11a). Immunohistochemistry showed that there were increased CD11b(+), CD11c(+ )and iNOS(+ )cells (myeloid leukocytes) in the papules, with relatively few CD3(+ )T cells. While efalizumab caused a decreased expression of CD11a on T cells, other circulating leukocytes from patients receiving this therapy often showed increased CD11b and CD11c. In the setting of an additional stimulus such as skin trauma, this may predispose to increased trafficking into the skin using these alternative β2 integrins. In addition, there may be impaired immune synapse formation, limiting the development of these lesions to small papules. There is little evidence for these papular lesions being "allergic" in nature as there are few eosinophils on biopsy, and they respond to minimal or no therapy even if efalizumab is continued. CONCLUSION: We hypothesize that these papules may represent a unique type of "mechanistic" inflammatory reaction, seen only in the context of drug-induced CD11a blockade, and not during the natural disease process
Lattice vibrations of alpha'-NaV2O5
We have measured far infrared reflectance and transmittance spectra as well
as Raman scattering spectra of \alpha'-NaV2O5 single crystals for all the
principal polarizations. The temperature range above the phase transition
temperature T_c=35 K was investigated, mainly. On the basis of this
experimental study and of the lattice dynamics calculations we conclude that
the symmetry of NaV2O5 in the high temperature phase is described by the
centrosymmetric D_{2h}^{13} space group. The assignment of the observed phonons
is given. Values of dielectric constants are obtained from the infrared data.
Asymmetric shapes of several infrared lines as well as higher order infrared
vibrational spectra are discussed. The crystal field energy levels of the 3d
electron localized at the V^{4+} site have been calculated in the framework of
the exchange charge model using the values of effective charges obtained from
the lattice dynamics calculations. According to the results of these
calculations, the earlier observed broad optical bands in the region of 1 eV
can be interpreted as phonon assisted d-d transitions.Comment: 12 pages, 8 figures, 5 tables; submitted to PR
The Prosensory Function of Sox2 in the Chicken Inner Ear Relies on the Direct Regulation of Atoh1
The proneural gene Atoh1 is crucial for the development of inner ear hair cells and it requires the function of the transcription factor Sox2 through yet unknown mechanisms. In the present work, we used the chicken embryo and HEK293T cells to explore the regulation of Atoh1 by Sox2. The results show that hair cells derive from Sox2-positive otic progenitors and that Sox2 directly activates Atoh1 through a transcriptional activator function that requires the integrity of Sox2 DNA binding domain. Atoh1 activation depends on Sox transcription factor binding sites (SoxTFBS) present in the Atoh1 3′ enhancer where Sox2 directly binds, as shown by site directed mutagenesis and chromatin immunoprecipitation (ChIP). In the inner ear, Atoh1 enhancer activity is detected in the neurosensory domain and it depends on Sox2. Dominant negative competition (Sox2HMG-Engrailed) and mutation of the SoxTFBS abolish the reporter activity in vivo. Moreover, ChIP assay in isolated otic vesicles shows that Sox2 is bound to the Atoh1 enhancer in vivo. However, besides activating Atoh1, Sox2 also promotes the expression of Atoh1 negative regulators and the temporal profile of Atoh1 activation by Sox2 is transient suggesting that Sox2 triggers an incoherent feed-forward loop. These results provide a mechanism for the prosensory function of Sox2 in the inner ear. We suggest that sensory competence is established early in otic development through the activation of Atoh1 by Sox2, however, hair cell differentiation is prevented until later stages by the parallel activation of negative regulators of Atoh1 function
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