175 research outputs found
Neuroanatomical dysmorphology of the medial superior olivary nucleus in sudden fetal and infant death
doi: 10.3389/fnhum.2012.00322 Neuroanatomical dysmorphology of the medial superior olivary nucleus in sudden fetal and infant deat
The age, origin and emplacement of the Tsiknias Ophiolite, Tinos, Greece
The Tsiknias Ophiolite, exposed at the highest structural levels of Tinos, Greece, represents a thrust sheet of Tethyan oceanic crust and upper mantle emplaced onto the AtticâCycladic Massif. We present new field observations and a new geological map of Tinos, integrated with petrology, THERMOCALC phase diagram modelling, UâPb geochronology and whole rock geochemistry, resulting in a tectonoâthermal model that describes the formation and emplacement of the Tsiknias Ophiolite and newly identified underlying metamorphic sole. The ophiolite comprises a succession of partially dismembered and structurally repeated ultramafic and gabbroic rocks that represent the Moho Transition Zone. A plagiogranite dated by UâPb zircon at 161.9 ± 2.8 Ma, reveals that the Tsiknias Ophiolite formed in a supraâsubduction zone setting, comparable to the âEastâVardar Ophiolitesâ, and was intruded by gabbros at 144.4 ± 5.6 Ma. Strongly sheared metamorphic sole rocks show a condensed and inverted metamorphic gradient, from partially anatectic amphibolites at PâT conditions of ca. 8.5 kbar 850â600 °C, downâstructural section to greenschistâfacies oceanic metasediments over ~250 m. Leucosomes generated by partial melting of the uppermost sole amphibolite, yielded a UâPb zircon protolith age of ca. 190 Ma and a highâgrade metamorphicâanatectic age of 74.0 ± 3.5 Ma associated with ophiolite emplacement. The Tsiknias Ophiolite was therefore obducted ~90 Myrs after it formed during initiation of a NEâdipping intraâoceanic subduction zone to the northeast of the Cyclades that coincides with Africa's plate motion changing from transcurrent to convergent. Continued subduction resulted in highâpressure metamorphism of the Cycladic continental margin ~25 Myrs later
The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to
The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria
The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to
The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria
A metodologia de Lamarck
Neste artigo, o mĂ©todo cientĂfico de Jean-Baptiste Lamarck Ă© estudado sob o ponto de vista de seu discurso metodolĂłgico, bem como sob o ponto de vista de sua prĂĄtica cientĂfica. Essa metodologia Ă© comparada Ă preconizada por Condillac, assim como Ă dos "ideĂłlogos" (idĂ©ologues) grupo no qual se costuma incluir o prĂłprio Lamarck. Mostra-se que o discurso metodolĂłgico de Lamarck assemelha-se ao dos ideĂłlogos; no entanto, sua prĂĄtica cientĂfica nĂŁo se coaduna com esse enfoque. Em vez de seguir uma abordagem empirista, a obra de Lamarck se fundamenta em princĂpios metafĂsicos gerais sobre a natureza. Sob o ponto de vista dos ideĂłlogos, seu trabalho deveria ser rejeitado - o que de fato ocorreu - como um mero sistema (systĂšme) metafĂsico - no sentido pejorativo utilizado pelos seguidores de Condillac. No entanto, o presente artigo argumenta que esse Ă© justamente um importante e inovador aspecto da obra de Lamarck, que permitiu a eclosĂŁo do evolucionismo moderno
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