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Structural Mechanisms (structural + mechanism)
Selected AbstractsStructural mechanisms of multidrug recognition and regulation by bacterial multidrug transcription factorsMOLECULAR MICROBIOLOGY, Issue 4 2002Maria A. Schumacher Summary The increase in bacterial resistance to multiple drugs represents a serious and growing health risk. One component of multidrug resistance (MDR) is a group of multidrug transporters that are often regulated at the transcriptional level by repressors and/or activators. Some of these transcription factors are also multidrug-binding proteins, frequently recognizing the same array of drugs that are effluxed by the transporters that they regulate. How a single protein can recognize such chemically disparate compounds is an intriguing question from a structural standpoint and an important question in future drug development endeavours. Unlike the multidrug transporters, the cytosolic multidrug-binding regulatory proteins are more tractable systems for structural analyses. Here, we describe recent crystallographic studies on MarR, BmrR and QacR, three bacterial transcription regulators that are also multidrug-binding proteins. Although our understanding of multidrug binding and transcriptional regulation by MarR is in its initial stages, the structure of a BmrR,TPP+,DNA complex has revealed important insights into the novel transcription activation mechanism of the MerR family, and the structures of a QacR,DNA complex and QacR bound to six different drugs have revealed not only the mechanism of induction of this repressor but has afforded the first view of any MDR protein bound to multiple drugs. [source] On silver wings: a fragile structural mechanism increases plumage conspicuousnessJOURNAL OF AVIAN BIOLOGY, Issue 5 2009Ismael Galván We report for the first time the existence of a structural mechanism of feathers different from iridescence that makes plumage conspicuous. By using electron and light microscopy, we show that the mechanism consists of special lengthened and twisted distal barbules that are very susceptible to damage. The dorsal side of these barbules is translucent, which creates a distinctive sheen colouration to feathers that otherwise would be dark. When distal sheen barbules are broken, the black proximal barbules are exposed, thus generating a conspicuous difference between abraded and non-abraded areas. Total and ultraviolet reflectance of sheen (non-abraded) areas are strikingly higher than in abraded areas. We propose that this mechanism represents a case of convergent evolution in species that are limited in developing colourful plumage patches. Future studies should explore the potential of this colour mechanism to act as a signal of individual quality or identity. [source] Cyclosporine Induces Epileptiform Activity in an In Vitro Seizure ModelEPILEPSIA, Issue 3 2000Michael Wong Summary: Purpose: Cyclosporine (CSA) toxicity represents a common cause of seizures in transplant patients, but the specific mechanisms by which CSA induces seizures are unknown. Although CSA may promote seizure activity by various metabolic, toxic, vascular, or structural mechanisms, CSA also has been hypothesized to modulate neuronal excitability directly. The objective of this study was to determine if CSA exerts direct epileptogenic actions on neurons in an in vitro seizure model. Methods: Combined hippocampal-entorhinal cortex slices from juvenile rats were exposed directly to artificial cerebro-spinal fluid (ACSF) containing either (a) 1.0 mM magnesium sulfate (control), (b) 1.0 mM sodium sulfate (low-magnesium), or (c) 1.0 mM magnesium sulfate + CSA (1,000,10,000 ng/ml). Spontaneous and evoked extracellular field potentials were recorded simultaneously from the dentate gyrus (DG) and CA3 hippocampal regions. Evoked synaptic responses were elicited by stimulation of the entorhinal cortex/perforant pathway. Results: CSA elicited spontaneous or stimulation-induced epileptiform activity in the DG or CA3 region of ,40% of slices, consisting of brief repetitive "interictal" discharges or prolonged stereotypical "ictal" discharges. Mean latency to epileptiform activity was ,100 min after onset of CSA application. The interictal discharges were inhibited by the non-NMDA antagonist, NBQX. Similar epileptiform activity was observed in low-magnesium ACSF without CSA. In control ACSF alone, epileptiform activity was not seen, except for rare spontaneous potentials in the DG. Conclusions: Direct effects of CSA on neuronal excitability and synaptic transmission may contribute to seizures seen in clinical CSA neurotoxicity. [source] Are House Wren Troglodytes aedon eggs unusually strong?IBIS, Issue 2 2002Test of the predicted effect of intraspecific egg destruction As a result of opposing selective forces, the external strength of avian eggs should be near some size-specific optimum. However, in certain situations there should be selection on females to lay unusually strong eggs. According to one hypothesis, intraspecific egg destruction should favour increased egg strength as a means of defence against conspecific intruders. This hypothesis predicts that House Wrens Troglodytes aedon, a species well known for its tendency to destroy conspecific clutches, should be under selection for unusually strong eggs. However, the intensity of selection for strong eggs should also be modified by efficacy of nest defence against conspecific intruders in a given species (i.e. efficient nest defence by the breeding pair should weaken selection for unusually strong eggs). The goals of our study were: (1) to establish whether House Wren eggs are stronger than expected for their size; (2) to determine which structural mechanisms are responsible for their unusual strength; and (3) to test a hypothesis that, between wren species, the efficacy of nest defence and the intensity of egg-destroying behaviour affect the intensity of selection for unusually strong eggs. Our results demonstrated that: (1) House Wren eggs are 1.9 times stronger than expected for their size; (2) their unusual strength is achieved mostly by their unusually thick shells; and (3) eggs of the House Wren (extensive paternal nest defence; male egg-destroying behaviour suppressed during incubation) are significantly weaker structurally than eggs of the Marsh Wren Cistothorus palustris (reduced paternal nest defence; male egg-destroying behaviour present throughout incubation). These results are consistent with the hypothesis that the intraspecific egg-destroying behaviour and the efficacy of nest defence by the breeding adults have played a role in the evolution of strength of House Wren eggs. [source] Simultaneous measurement of resistance and viscoelastic responses of carbon black-filled high-density polyethylene subjected to dynamic torsionJOURNAL OF APPLIED POLYMER SCIENCE, Issue 4 2008Jianfeng Zhou Abstract The conduction and viscoelastic responses to temperature are measured simultaneously for carbon black (CB) filled high-density polyethylene (HDPE) subjected to dynamic torsion. PTC/NTC transition was correlated with the loss tangent peak and the quasi modulus plateau, which was ascribed to the filler network. The bond-bending model of elastic percolation networks was used to reveal the structural mechanisms for the cyclic resistance changes at different temperatures. The resistance changes at lower temperatures depended on the deformation of the polymer matrix, while the changes in melting state were mainly attributed to the rearrangement of the CB network. A simple scaling law is derived to relate resistance and dynamic storage modulus in the melting region. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Developing organizational learning in the NHSMEDICAL EDUCATION, Issue 1 2001Sandra M Nutley Learning has been identified as a central concern for a modernized NHS. Continuing professional development has an important role to play in improving learning but there is also a need to pay more attention to collective (organizational) learning. Such learning is concerned with the way organizations build and organize knowledge. Recent emphasis within the NHS has been on the codification of individual and collective knowledge , for example, guidelines and National Service Frameworks. This needs to be balanced by more personalized knowledge management strategies, especially when dealing with innovative services that rely on tacit knowledge to solve problems. Having robust systems for storing and communicating knowledge is only one part of the challenge. It is also important to consider how such knowledge gets used, and how routines become established within organizations that structure the way in which knowledge is deployed. In many organizations these routines favour the adaptive use of knowledge, which helps organizations to achieve incremental improvements to existing practices. However, the development of organizational learning in the NHS needs to move beyond adaptive (single loop) learning, to foster skills in generative (double loop) learning and meta-learning. Such learning leads to a redefinition of the organization's goals, norms, policies, procedures or even structures. This paper argues that moving the NHS in this direction will require attention to the cultural values and structural mechanisms that facilitate organizational learning. [source] Crystal structures of truncated alphaA and alphaB crystallins reveal structural mechanisms of polydispersity important for eye lens functionPROTEIN SCIENCE, Issue 5 2010Arthur Laganowsky Abstract Small heat shock proteins alphaA and alphaB crystallin form highly polydisperse oligomers that frustrate protein aggregation, crystallization, and amyloid formation. Here, we present the crystal structures of truncated forms of bovine alphaA crystallin (AAC59,163) and human alphaB crystallin (ABC68,162), both containing the C-terminal extension that functions in chaperone action and oligomeric assembly. In both structures, the C-terminal extensions swap into neighboring molecules, creating runaway domain swaps. This interface, termed DS, enables crystallin polydispersity because the C-terminal extension is palindromic and thereby allows the formation of equivalent residue interactions in both directions. That is, we observe that the extension binds in opposite directions at the DS interfaces of AAC59,163 and ABC68,162. A second dimeric interface, termed AP, also enables polydispersity by forming an antiparallel beta sheet with three distinct registration shifts. These two polymorphic interfaces enforce polydispersity of alpha crystallin. This evolved polydispersity suggests molecular mechanisms for chaperone action and for prevention of crystallization, both necessary for transparency of eye lenses. [source] | |||||||||||||