118 research outputs found
Selective Blockade of Trypanosomatid Protein Synthesis by a Recombinant Antibody Anti-Trypanosoma cruzi P2ÎČ Protein
The ribosomal P proteins are located on the stalk of the ribosomal large subunit and play a critical role during the elongation step of protein synthesis. The single chain recombinant antibody C5 (scFv C5) directed against the C-terminal region of the Trypanosoma cruzi P2ÎČ protein (TcP2ÎČ) recognizes the conserved C-terminal end of all T. cruzi ribosomal P proteins. Although this region is highly conserved among different species, surface plasmon resonance analysis showed that the scFv C5 possesses very low affinity for the corresponding mammalian epitope, despite having only one single amino-acid change. Crystallographic analysis, in silico modelization and NMR assays support the analysis, increasing our understanding on the structural basis of epitope specificity. In vitro protein synthesis experiments showed that scFv C5 was able to specifically block translation by T. cruzi and Crithidia fasciculata ribosomes, but virtually had no effect on Rattus norvegicus ribosomes. Therefore, we used the scFv C5 coding sequence to make inducible intrabodies in Trypanosoma brucei. Transgenic parasites showed a strong decrease in their growth rate after induction. These results strengthen the importance of the P protein C terminal regions for ribosomal translation activity and suggest that trypanosomatid ribosomal P proteins could be a possible target for selective therapeutic agents that could be derived from structural analysis of the scFv C5 antibody paratope
El Acuerdo Bruselas 2017 para Latinoamérica: una iniciativa de la GARD y SLaai
Abstract The Global Alliance against Chronic Respiratory Diseases (GARD) is a network of organizations coordinated by the World Health Organization. It is a voluntary alliance of national and international organizations, institutions and agencies with global scope that are committed with actions to improve access to prevention, care and essential medications. On its last annual meeting, celebrated in Brussels (Belgium) in September 2017, the need for actions and representation to be grouped by geographic regions was discussed. There are several successful programs regarding morbidity and mortality control of these diseases, and others that improve cost-beneïŹ t and quality of life. Thus, SLaai proposes to contribute to the diïŹ usion and knowledge of chronic respiratory diseases magnitude and risk factors, to identify successful programs in Latin America in order for them to be replicated in the region and to generate strategic alliances for the strengthening of joint actions.
Keywords: Alliance; Respiratory diseases; Programs; Action
SoluciĂłn de problemas
7. Las sumas 1 +1/2+1/3.......+1/n         (n = 2, 3, 4, ... ) no son jamĂĄs nĂșmeros entero
The Role of Native Language and the Fundamental Design of the Auditory System in Detecting Rhythm Changes
Accepted December 13, 2018Purpose: We investigated whether rhythm discrimination
is mainly driven by the native language of the listener or
by the fundamental design of the human auditory system
and universal cognitive mechanisms shared by all people
irrespective of rhythmic patterns in their native language.
Method: In multiple experiments, we asked participants to
listen to 2 continuous acoustic sequences and to determine
whether their rhythms were the same or different (AX
discrimination). Participants were native speakers of
4 languages with different rhythmic properties (Spanish,
French, English, and German) to understand whether the
predominant rhythmic patterns of a native language affect
sensitivity, bias, and reaction time in detecting rhythmic
changes in linguistic (Experiment 2) and in nonlinguistic
(Experiments 1 and 2) acoustic sequences. We examined
sensitivity and bias measures, as well as reaction times.
We also computed Bayes factors in order to assess the
effect of native language.
Results: All listeners performed better (i.e., responded
faster and manifested higher sensitivity and accuracy)
when detecting the presence or absence of a rhythm
change when the 1st stimulus in an AX test pair exhibited
regular rhythm (i.e., a syllable-timed rhythmic pattern)
than when the 1st stimulus exhibited irregular rhythm (i.e.,
stress-timed rhythmic pattern). This result pattern was
observed both on linguistic and nonlinguistic stimuli
and was not modulated by the native language of the
participant.
Conclusion: We conclude that rhythm change detection is
a fundamental function of a processing system that relies
on general auditory mechanisms and is not modulated by
linguistic experience.The authors acknowledge support from Spanish Ministry of Economy and Competitiveness Grant PSI2017-82563-P (awarded to A. G. S.), the âSevero Ochoaâ Programme for Centres/Units of Excellence in R&D Grant SEV-2015-490 (BCBL), and the Basque Foundation for Science Grant IKERBASQUE (awarded to A. G. S. and M. O.). D. M. G. was supported by Grant PIA/Basal FB0003 from the Chilean Research Council. L. P. was supported by the Spanish Ministry of Economy and Competitiveness via Juan de la Cierva fellowship
Towards a Combined Use of Geophysics and Remote Sensing Techniques for the Characterization of a Singular Building: âEl TorreĂłnâ (the Tower) at Ulaca Oppidum (Solosancho, Ăvila, Spain)
This research focuses on the study of the ruins of a large building known as âEl TorreĂłnâ (the Tower), belonging to the Ulaca oppidum (Solosancho, Province of Ăvila, Spain). Different remote sensing and geophysical approaches have been used to fulfil this objective, providing a better understanding of the buildingâs functionality in this town, which belongs to the Late Iron Age (ca. 300â50 BCE). In this sense, the outer limits of the ruins have been identified using photogrammetry and convergent drone flights. An additional drone flight was conducted in the surrounding area to find additional data that could be used for more global interpretations. Magnetometry was used to analyze the underground bedrock structure and ground penetrating radar (GPR) was employed to evaluate the internal layout of the ruins. The combination of these digital methodologies (surface and underground) has provided a new perspective for the improved interpretation of âEl TorreĂłnâ and its characteristics. Research of this type presents additional guidelines for better understanding of the role of this structure with regards to other buildings in the Ulaca oppidum. The results of these studies will additionally allow archaeologists to better plan future interventions while presenting new data that can be used for the interpretation of this archaeological complex on a larger scale
Latin American anaphylaxis registry
Background: Recent data about clinical features, triggers and management of anaphylaxis in Latin America is lacking. Objective: To provide updated and extended data on anaphylaxis in this region. Method: An online questionnaire was used, with 67 allergy units involved from 12 Latin-American countries and Spain. Among data recorded, demographic information, clinical features, severity, triggering agents, and treatment were received. Results: Eight hundred and seventeen anaphylactic reactions were recorded. No difference in severity, regardless of pre-existing allergy or asthma history was found. Drug induced anaphylaxis (DIA) was most frequent (40.6%), followed by food induced anaphylaxis (FIA) (32.9%) and venom induced anaphylaxis (VIA) (12%). FIA and VIA were more common in children-adolescents. Non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibiotics (BLA) were the most frequent drugs involved. Milk (61.1% of FIA) and egg (15.4% of FIA) in children, and shellfish (25.5% of FIA), fresh fruits (14.2% of FIA), and fish (11.3% of FIA) in adults were the most common FIA triggers. Fire ants were the most frequent insect triggers, and they induced more severe reactions than triggers of FIA and DIA (p < 0.0001). Epinephrine was used in 43.8% of anaphylaxis episodes. After Emergency Department treatment, epinephrine was prescribed to 13% of patients. Conclusions: Drugs (NSAIDs and BLA), foods (milk and egg in children and shellfish, fruits and fish in adults) and fire ants were the most common inducers of anaphylaxis. Epinephrine was used in less than half of the episodes emphasizing the urgent need to improve dissemination and implementation of anaphylaxis guidelines.RevisiĂłn por pare
Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper
The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano-technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in-depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody- (I-III), cell-mediated (IVa-c), tissue-driven mechanisms (V-VI) and direct response to chemicals (VII). Types I-III are linked to classical and newly described clinical conditions. Type IVa-c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V-VI involve epithelial barrier defects and metabolic-induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime
IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper
Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen
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