328 research outputs found
Interaction of Variable Bacterial Outer Membrane Lipoproteins with Brain Endothelium
Previously we reported that the variable outer membrane lipoprotein Vsp1 from the relapsing fever spirochete Borrelia turicatae disseminates from blood to brain better than the closely related Vsp2 [1]. Here we studied the interaction between Vsp1 and Vsp2 with brain endothelium in more detail.We compared Vsp1 to Vsp2 using human brain microvascular endothelial cell (HBMEC) association assays with aminoacid radiolabeled Vsp-expressing clones of recombinant Borrelia burgdorferi and lanthanide-labeled purified lipidated Vsp1 (LVsp1) and Vsp2 (LVsp2) and inoculations of the lanthanide-labeled proteins into mice. The results showed that heterologous expression of LVsp1 or LVsp2 in B. burgdorferi increased its association with HBMEC to a similar degree. Purified lanthanide-labeled lipidated Vsp1 (LVsp1) and LVsp2 by themselves were capable of associating with HBMEC. The association of LVsp1 with brain endothelium was time-dependent, saturable, and required the lipidation. The association of Vsp1 with HBMEC was inhibited by incubation at lower temperature or with excess unlabeled LVsp1 or LVsp2 but not with excess rVsp1 or mouse albumin or an anti Vsp1 monoclonal antibody. The association of LVsp2 with HBMEC and its movement from blood to brain parenchyma significantly increased in the presence of LVsp1.Variable bacterial outer membrane lipoproteins interact with brain endothelium differently; the lipidation and variable features at the protein dome region are key modulators of this interaction
Binding binding: Departure points for a different version of the perceptual retouch theory
In the perceptual retouch theory, masking and related microgenetic phenomena were
explained as a result of interaction between specific cortical representational
systems and the non-specific sub-cortical modulation system. Masking appears as
deprivation of sufficient modulation of the consciousness mechanism suffered by
the target-specific signals because of the temporal delay of non-specific
modulation (necessary for conscious representation), which explicates the
later-coming mask information instead of the already decayed target information.
The core of the model envisaged relative magnitudes of EPSPs of single cortical
cells driven by target and mask signals at the moment when the nonspecific,
presynaptic, excitatory input arrives from the thalamus. In the light of the
current evidence about the importance of synchronised activity of specific and
non-specific systems in generating consciousness, the retouch theory requires
perhaps a different view. This article presents some premises for modification
of the retouch theory, where instead of the cumulative presynaptic spike
activities and EPSPs of single cells, the oscillatory activity in the gamma
range of the participating systems is considered and shown to be consistent with
the basic ideas of the retouch theory. In this conceptualisation, O-binding
refers to specific encoding which is based on gamma-band synchronised
oscillations in the activity of specific cortical sensory modules that represent
features and objects; C-binding refers to the gamma-band oscillations in the
activity of the non-specific thalamic systems, which is necessary for the
O-binding based data to become consciously experienced
Circuit-based interrogation of sleep control.
Sleep is a fundamental biological process observed widely in the animal kingdom, but the neural circuits generating sleep remain poorly understood. Understanding the brain mechanisms controlling sleep requires the identification of key neurons in the control circuits and mapping of their synaptic connections. Technical innovations over the past decade have greatly facilitated dissection of the sleep circuits. This has set the stage for understanding how a variety of environmental and physiological factors influence sleep. The ability to initiate and terminate sleep on command will also help us to elucidate its functions within and beyond the brain
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