1,559 research outputs found
Electrostatic Steering Accelerates C3d:CR2 Association.
Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts
Minocycline protects against delayed cerebral ischemia after subarachnoid hemorrhage via matrix metalloproteinase-9 inhibition
Optical Dipole Structure and Orientation of GaN Defect Single-Photon Emitters
GaN has recently been shown to host bright, photostable, defect single photon
emitters in the 600-700 nm wavelength range that are promising for quantum
applications. The nature and origin of these defect emitters remain elusive. In
this work, we study the optical dipole structures and orientations of these
defect emitters using the defocused imaging technique. In this technique, the
far-field radiation pattern of an emitter in the Fourier plane is imaged to
obtain information about the structure of the optical dipole moment and its
orientation in 3D. Our experimental results, backed by numerical simulations,
show that these defect emitters in GaN exhibit a single dipole moment that is
oriented almost perpendicular to the wurtzite crystal c-axis. Data collected
from many different emitters shows that the angular orientation of the dipole
moment in the plane perpendicular to the c-axis exhibits a distribution that
shows peaks centered at the angles corresponding to the nearest Ga-N bonds and
also at the angles corresponding to the nearest Ga-Ga (or N-N) directions.
Moreover, the in-plane angular distribution shows little difference among
defect emitters with different emission wavelengths in the 600-700 nm range.
Our work sheds light on the nature and origin of these GaN defect emitters.Comment: 15 pages, 4 figure
Shear induced instabilities in layered liquids
Motivated by the experimentally observed shear-induced destabilization and
reorientation of smectic A like systems, we consider an extended formulation of
smectic A hydrodynamics. We include both, the smectic layering (via the layer
displacement u and the layer normal p) and the director n of the underlying
nematic order in our macroscopic hydrodynamic description and allow both
directions to differ in non equilibrium situations. In an homeotropically
aligned sample the nematic director does couple to an applied simple shear,
whereas the smectic layering stays unchanged. This difference leads to a finite
(but usually small) angle between n and p, which we find to be equivalent to an
effective dilatation of the layers. This effective dilatation leads, above a
certain threshold, to an undulation instability of the layers. We generalize
our earlier approach [Rheol. Acta, vol.39(3), 15] and include the cross
couplings with the velocity field and the order parameters for orientational
and positional order and show how the order parameters interact with the
undulation instability. We explore the influence of various material parameters
on the instability. Comparing our results to recent experiments and molecular
dynamic simulations, we find a good qualitative agreement.Comment: 15 pages, 12 figures, accepted for publication in PR
Osteopathology and insect traces in the Australopithecus africanus skeleton StW 431
We present the first application of high-resolution micro computed tomography in an analysis of both the internal and external morphology of the lumbar region of StW 431 – a hominin skeleton recovered from Member 4 infill of the Sterkfontein Caves (South Africa) in 1987. The lumbar vertebrae of the individual present a number of proliferative and erosive bony processes, which were investigated in this study. Investigations suggest a complex history of taphonomic alteration to pre-existing spinal degenerative joint disease (SDJD) as well as post-mortem modification by an unknown insect. This study is in agreement
with previous pathological diagnoses of SDJD which affected StW 431 and is the first time insect traces on this hominin are described. The results of this analysis attest to the complex series of post-mortem processes affecting the Sterkfontein site and its fossil assemblages
Conformational changes of calmodulin upon Ca2+ binding studied with a microfluidic mixer
A microfluidic mixer is applied to study the kinetics of calmodulin conformational changes upon Ca2+ binding. The device facilitates rapid, uniform mixing by decoupling hydrodynamic focusing from diffusive mixing and accesses time scales of tens of microseconds. The mixer is used in conjunction with multiphoton microscopy to examine the fast Ca2+-induced transitions of acrylodan-labeled calmodulin. We find that the kinetic rates of the conformational changes in two homologous globular domains differ by more than an order of magnitude. The characteristic time constants are ≈490 μs for the transitions in the C-terminal domain and ≈20 ms for those in the N-terminal domain of the protein. We discuss possible mechanisms for the two distinct events and the biological role of the stable intermediate, half-saturated calmodulin
- …