100 research outputs found
Monetary Policy and Banking Supervision Functions on the Central Bank
This paper analyzes the advantages and disadvantages of maintaining the banking supervisory functions at the Banco Central do Brasil (BCB). First, these pros and cons are identified and listed using the economic literature, after a brief analysis of the ongoing debate and international experience regarding monetary policy, independence of the central bank and banking supervision. Then it is discussed the international tendencies as related to central bank reforms and the respective supervisory systems, including an annex panel of the experience of 40 different countries. The first and clearest tendency identified is to withdraw supervisory functions from the monetary authorities, normally seen as capable of strengthening the "central bank independence". The second trend - and one that seems to be gaining strength - is merger of the agencies charged with banking, securities and insurance supervision into a single agency, enhancing their capacity to perform the financial groups' consolidated supervision. There is no firm conclusion as the more effective institutional arrangement related to banking supervision under the control of the central bank or another institution.
Bancos Oficiais e CrĂ©dito Direcionado â o que diferencia o mercado de crĂ©dito brasileiro?
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O desequilĂbrio financeiro do setor pĂșblico: restrição externa, restrição orçamentĂĄria e restrição monetĂĄria - uma nota
O desequilĂbrio financeiro do setor pĂșblico Ă© hoje, sem dĂșvida, um dos maiores problemas a serem superados pelas autoridades governamentais, sem o qual se torna difĂcil uma redução nas taxas de juros domĂ©sticas (...
Hormone affinity and fibril formation of piscine transthyretin: the role of the N-terminal
Transthyretin (TTR) transports thyroid hormones (THs), thyroxine (T4) and
triiodothyronine (T3) in the blood of vertebrates. TH-binding sites are highly conserved in vertebrate TTR however, piscine TTR has a longer N-terminus which is thought to influence TH-binding affinity and may influence TTR stability. We produced
recombinant wild-type sea bream TTR (sbTTRWT) plus two mutants in which six
(sbTTRM6) and twelve (sbTTRM12) N-terminal residues were removed. Ligandbinding
studies revealed similar affinities for T3 (Kd=10.6±1.7nM) and T4 (Kd=9.8±0.97nM) binding to sbTTRWT. Affinity for THs was unaltered in sbTTRM12 but sbTTRM6 had poorer affinity for T4 (Kd=252.3±15.8nM) implying that some residues in the N-terminus can influence T4 binding. sbTTRM6 inhibited acid-mediated fibril formation in vitro as shown by fluorometric measurements using thioflavine-T.In contrast, fibril formation by sbTTRM12 was significant, probably due to decreased stability of the tetramer. Such studies also suggested that sbTTRWT is more resistant to fibril formation than human TTR
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Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases.
Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular and interorgan communication. The capability to modulate their stability, tissue-specific targeting and cargo render EVs as promising nanotherapeutics for treating heart, lung, blood and sleep (HLBS) diseases. However, current limitations in large-scale manufacturing of therapeutic-grade EVs, and knowledge gaps in EV biogenesis and heterogeneity pose significant challenges in their clinical application as diagnostics or therapeutics for HLBS diseases. To address these challenges, a strategic workshop with multidisciplinary experts in EV biology and U.S. Food and Drug Administration (USFDA) officials was convened by the National Heart, Lung and Blood Institute. The presentations and discussions were focused on summarizing the current state of science and technology for engineering therapeutic EVs for HLBS diseases, identifying critical knowledge gaps and regulatory challenges and suggesting potential solutions to promulgate translation of therapeutic EVs to the clinic. Benchmarks to meet the critical quality attributes set by the USFDA for other cell-based therapeutics were discussed. Development of novel strategies and approaches for scaling-up EV production and the quality control/quality analysis (QC/QA) of EV-based therapeutics were recognized as the necessary milestones for future investigations.Funding information:
National Heart, Lung, and Blood Institute,
Grant/Award Numbers: HL 122596, HL124021,
HL124074, HL128297, HL141080, HL155346-01,
R35HL150807, R56HL141206
Prithu Sundd was supported by NIH-NHLBI R01 grants (HL128297 and HL141080) and 18TPA34170588 from American Heart
Association. Stephen Y. Chan was supported by NIH grants R01 HL124021 and HL 122596 as well as AHA grant 18EIA33900027.
SuamyaDaswas supported by NIH grants R35HL150807, UH3 TR002878 andAHASFRN35120123. ZhenjiaWangwas supported
by NIH grant (R01EB027078). Pilar MartĂn was supported by MCIN-ISCIII-Fondo de InvestigaciĂłn Sanitaria grant PI22/01759.
KennethW.Witwer was supported in part by NIH grants R01AI144997, R01DA047807, R33MH118164 andUH3CA241694. Tianji
Chen was supported by AHA Career Development Award 18CDA34110301, Gilead Sciences Research Scholars Program in PAH,
NIH-NHLBI grant R56HL141206 and Chicago Biomedical ConsortiumCatalyst Award. EduardoMarbĂĄn was supported byNIH
R01 HL124074 and HL155346-01.S
Erythrocytes from patients with type 2 diabetes induce endothelial dysfunction via arginase I.
BACKGROUND: Cardiovascular complications are major clinical problems in type 2 diabetes mellitus (T2DM). The authors previously demonstrated a crucial role of red blood cells (RBCs) in control of cardiac function through arginase-dependent regulation of nitric oxide export from RBCs. There is alteration of RBC function, as well as an increase in arginase activity, in T2DM. OBJECTIVES: The authors hypothesized that RBCs from patients with T2DM induce endothelial dysfunction by up-regulation of arginase. METHODS: RBCs were isolated from patients with T2DM and age-matched healthy subjects and were incubated with rat aortas or human internal mammary arteries from nondiabetic patients for vascular reactivity and biochemical studies. RESULTS: Arginase activity and arginase I protein expression were elevated in RBCs from patients with T2DM (T2DM RBCs) through an effect induced by reactive oxygen species (ROS). Co-incubation of arterial segments with T2DM RBCs, but not RBCs from age-matched healthy subjects, significantly impaired endothelial function but not smooth muscle cell function in both healthy rat aortas and human internal mammary arteries. Endothelial dysfunction induced by T2DM RBCs was prevented by inhibition of arginase and ROS both at the RBC and vascular levels. T2DM RBCs induced increased vascular arginase I expression and activity through an ROS-dependent mechanism. CONCLUSIONS: This study demonstrates a novel mechanism behind endothelial dysfunction in T2DM that is induced by RBC arginase I and ROS. Targeting arginase I in RBCs may serve as a novel therapeutic tool for the treatment of endothelial dysfunction in T2DM
Genus Paracoccidioides: Species Recognition and Biogeographic Aspects
Background: Paracoccidioidomycosis is a systemic mycosis caused by Paracoccidioides brasiliensis (species S1, PS2, PS3), and Paracoccidioides lutzii. This work aimed to differentiate species within the genus Paracoccidioides, without applying multilocus sequencing, as well as to obtain knowledge of the possible speciation processes. Methodology/Principal Findings:
Single nucleotide polymorphism analysis on GP43, ARF and PRP8 intein genes successfully distinguished isolates into four different species. Morphological evaluation indicated that elongated conidia were observed exclusively in P. lutzii isolates, while all other species (S1, PS2 and PS3) were indistinguishable. To evaluate the biogeographic events that led to the current geographic distribution of Paracoccidioides species and their sister species, Nested Clade and Likelihood Analysis of Geographic Range Evolution (LAGRANGE) analyses were applied. The radiation of Paracoccidioides started in northwest South America, around 11â32 million years ago, as calculated on the basis of ARF substitution rate, in the BEAST program. Vicariance was responsible for the divergence among S1, PS2 and P. lutzii and a recent dispersal generated the PS3 species, restricted to Colombia. Taking into account the ancestral areas revealed by the LAGRANGE analysis and the major geographic distribution of L. loboi in the Amazon basin, a region strongly affected by the Andes uplift and marine incursions in the Cenozoic era, we also speculate about the effect of these geological events on the vicariance between Paracoccidioides and L. loboi. Conclusions/Significance: The use of at least 3 SNPs, but not morphological criteria, as markers allows us to distinguish among the four cryptic species of the genus Paracoccidioides. The work also presents a biogeographic study speculating on how these species might have diverged in South America, thus contributing to elucidating evolutionary aspects of the genus Paracoccidioides
Search for dark matter produced in association with bottom or top quarks in âs = 13 TeV pp collisions with the ATLAS detector
A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fbâ1 of protonâproton collision data recorded by the ATLAS experiment at âs = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
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