249 research outputs found
Unveiling the kinomes of leishmania infantum and L. braziliensis empowers the discovery of new kinase targets and antileishmanial compounds
Leishmaniasis is a neglected tropical disease caused by parasites of the genus Leishmania (NTD) endemic in 98 countries. Although some drugs are available, current treatments deal with issues such as toxicity, low efficacy, and emergence of resistance. Therefore, there is an urgent need to identify new targets for the development of new antileishmanial drugs. Protein kinases (PKs), which play an essential role in many biological processes, have become potential drug targets for many parasitic diseases. A refined bioinformatics pipeline was applied in order to define and compare the kinomes of L. infantum and L. braziliensis, species that cause cutaneous and visceral manifestations of leishmaniasis in the Americas, the latter being potentially fatal if untreated. Respectively, 224 and 221 PKs were identified in L. infantum and L. braziliensis overall. Almost all unclassified eukaryotic PKs were assigned to six of nine major kinase groups and, consequently, most have been classified into family and subfamily. Furthermore, revealing the kinomes for both Leishmania species allowed for the prioritization of potential drug targets that could be explored for discovering new drugs against leishmaniasis. Finally, we used a drug repurposing approach and prioritized seven approved drugs and investigational compounds to be experimentally tested against Leishmania. Trametinib and NMS-1286937 inhibited the growth of L. infantum and L. braziliensis promastigotes and amastigotes and therefore might be good candidates for the drug repurposing pipeline17352361FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE GOIÁS - FAPE
Trastuzumab-Induced Myocardiotoxicity Mimicking Acute Coronary Syndrome
Trastuzumab is an important biological agent in the treatment of HER2-positive breast cancer, with effects on response rates, progression-free survival, overall survival and quality of life. Although this drug is well tolerated in terms of adverse effects, trastuzumab-associated myocardiotoxicity has been described to have an incidence of 0.6–4.5% and in rare cases, the drug can trigger severe congestive heart failure with progression to death or even mimic acute coronary syndrome with complete left bundle branch blockade. In this paper is reported a case of trastuzumab-associated myocardiotoxicity manifesting as acute coronary syndrome in a 69-year-old female. The patient is currently undergoing a conservative clinical treatment that restricts overexertion
Order and nFl Behavior in UCu4Pd
We have studied the role of disorder in the non-Fermi liquid system UCu4Pd
using annealing as a control parameter. Measurement of the lattice parameter
indicates that this procedure increases the crystallographic order by
rearranging the Pd atoms from the 16e to the 4c sites. We find that the low
temperature properties depend strongly on annealing. Whereas the non-Fermi
liquid behavior in the specific heat can be observed over a larger temperature
range after annealing, the clear non-Fermi liquid behavior of the resistivity
of the unannealed sample below 10 K disappears. We come to the conclusion that
this argues against the Kondo disorder model as an explanation for the
non-Fermi liquid properties of both as-prepared and annealed UCu4Pd
On the synonymy of Stictocephala alta (Walker) and Thelia constans Walker (Hemiptera: Membracidae)
Anemia hemolítica causada por Indigofera suffruticosa (Leg. Papilionoideae) em bovinos
How does the electromagnetic field couple to gravity, in particular to metric, nonmetricity, torsion, and curvature?
The coupling of the electromagnetic field to gravity is an age-old problem.
Presently, there is a resurgence of interest in it, mainly for two reasons: (i)
Experimental investigations are under way with ever increasing precision, be it
in the laboratory or by observing outer space. (ii) One desires to test out
alternatives to Einstein's gravitational theory, in particular those of a
gauge-theoretical nature, like Einstein-Cartan theory or metric-affine gravity.
A clean discussion requires a reflection on the foundations of electrodynamics.
If one bases electrodynamics on the conservation laws of electric charge and
magnetic flux, one finds Maxwell's equations expressed in terms of the
excitation H=(D,H) and the field strength F=(E,B) without any intervention of
the metric or the linear connection of spacetime. In other words, there is
still no coupling to gravity. Only the constitutive law H= functional(F)
mediates such a coupling. We discuss the different ways of how metric,
nonmetricity, torsion, and curvature can come into play here. Along the way, we
touch on non-local laws (Mashhoon), non-linear ones (Born-Infeld,
Heisenberg-Euler, Plebanski), linear ones, including the Abelian axion (Ni),
and find a method for deriving the metric from linear electrodynamics (Toupin,
Schoenberg). Finally, we discuss possible non-minimal coupling schemes.Comment: Latex2e, 26 pages. Contribution to "Testing Relativistic Gravity in
Space: Gyroscopes, Clocks, Interferometers ...", Proceedings of the 220th
Heraeus-Seminar, 22 - 27 August 1999 in Bad Honnef, C. Laemmerzahl et al.
(eds.). Springer, Berlin (2000) to be published (Revised version uses
Springer Latex macros; Sec. 6 substantially rewritten; appendices removed;
the list of references updated
Action of mouthwashes on Staphylococcus spp: isolated in the saliva of community and hospitalized individuals
Caracterização e relacionamento antigênico de três novos Bunyavirus no grupo Anopheles A (Bunyaviridae) dos arbovirus
Intoxicação experimental pelas favas de Stryphnodendron obovatum (Leg. Mimosoideae) em bovinos. 1. Caracterização do quadro clínico
Ecologia de mosquitos (Diptera: Culicidae) em criadouros naturais e artificiais de área rural do Norte do Estado do Paraná, Brasil: l - Coletas ao longo do leito de ribeirão
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