287 research outputs found
Subtle pH differences trigger single residue motions for moderating conformations of calmodulin
This study reveals the essence of ligand recognition mechanisms by which calmodulin (CaM) controls a variety of Ca2+ signaling processes. We study eight forms of calcium-loaded CaM each with distinct conformational states. Reducing the structure to two degrees of freedom conveniently describes main features of the conformational changes of CaM via simultaneous twist-bend motions of the two lobes. We utilize perturbation-response scanning (PRS) technique, coupled with molecular dynamics simulations. PRS is based on linear response theory, comprising sequential application of directed forces on selected residues followed by recording the resulting protein coordinates. We analyze directional preferences of the perturbations and resulting conformational changes. Manipulation of a single residue reproduces the structural change more effectively than that of single/pairs/triplets of collective modes of motion. Our findings also give information on how the flexible linker acts as a transducer of binding information to distant parts of the protein. Furthermore, by perturbing residue E31 located in one of the EF hand motifs in a specific direction, it is possible to induce conformational change relevant to five target structures. Independently, using four different pKa calculation strategies, we find this particular residue to be the charged residue (out of a total of 52), whose ionization state is most sensitive to subtle pH variations in the physiological range. It is plausible that at relatively low pH, CaM structure is less flexible. By gaining charged states at specific sites at a pH value around 7, such as E31 found in the present study, local conformational changes in the protein will lead to shifts in the energy landscape, paving the way to other conformational states. These findings are in accordance with Fluorescence Resonance Energy Transfer (FRET) measured shifts in conformational distributions towards more compact forms with decreased pH. They also corroborate mutational studies and proteolysis results which point to the significant role of E31 in CaM dynamics
Genome sequence of Acetomicrobium hydrogeniformans OS1
Acetomicrobium hydrogeniformans, an obligate anaerobe of the phylum Synergistetes, was isolated from oil production water. It has the unusual ability to produce almost 4 molecules H2/molecule glucose. The draft genome of A. hydrogeniformans OS1 (DSM 22491T) is 2,123,925 bp, with 2,068 coding sequences and 60 RNA genes
The Extreme Behavior of the Radio-loud Narrow-line Seyfert 1 Galaxy J0849+5108
Simultaneous radio, optical (both photometry and polarimetry), X-ray, and γ-ray observations of the radio-loud narrow-line Seyfert 1 (RL-NLSy1) galaxy J0849+5108 are presented. A massive three-magnitude optical flare across five nights in 2013 April is detected, along with associated flux increases in the γ-ray, infrared, and radio regimes; no comparable event was detected in the X-rays, though this may be due to poor coverage. A spectral energy distribution (SED) for the object using quasi-simultaneous data centered on the optical flare is compared to the previously published SEDs for the object by D'Ammando et al. The flare event coincided with a high degree of optical polarization. High amplitude optical microvariability is clearly detected, and is found to be of comparable amplitude when the object is observed in both faint and bright states. The object is also seen to undergo rapid shifts in polarization in both degree and electric vector position angle within a single night. J0849+5108 appears to show even more extreme variability than that previously reported for the similar object J0948+0022. These observations appear to support the growing claim that some RL-NLSy1 galaxies constitute a sub-class of blazar-like active galactic nuclei
The Columbia, Missouri, Heat Island Experiment (COHIX) and the Influence of a Small City on the Local Climatology
The heat island effect is a well known feature in the microclimate of urban areas but only a few studies have addressed the effect for smaller urban areas. We examine here the impact of Columbia, Missouri and the University of Missouri campus on the microclimate (temperature and precipitation) of central Missouri. We purchased twenty Radio Shack® digital Max/Min thermometers and ten standard raised-edge rain gauges and these were given to students, staff, and faculty participants who were chosen for their reliability to provide daily data over the course of a year, site the instrument, and their location (in order to provide
reasonable coverage locally). We also included information provided by automated and cooperative weather stations, and the weather station at the regional airport located 11 km (7 miles) southeast of Columbia. Our results indicate that the city has no discernable impact on the distribution of monthly precipitation totals. We found a distinct urban influence on the local surface temperatures, and the inner city region and the urbanized area of south Columbia were approximately 2 - 3 oF (1.0 - 1.5 oC) warmer in the mean than the surrounding environment. This difference grows to 3 - 6 oF (1.5 - 3.5 oC) when comparing the mean of the warmest station in the city to that of coolest station outside Columbia. We also observed a seasonal influence, as the heat island effect was more evident in the mean monthly maximum
(minimum) temperatures during the warmest (coldest) months
Subtle pH differences trigger single residue motions for moderating conformations of calmodulin
This study reveals the essence of ligand recognition mechanisms by which
calmodulin (CaM) controls a variety of Ca2+ signaling processes. We study eight
forms of calcium-loaded CaM each with distinct conformational states. Reducing
the structure to two degrees of freedom conveniently describes main features of
conformational changes of CaM via simultaneous twist-bend motions of the two
lobes. We utilize perturbation-response scanning (PRS) technique, coupled with
molecular dynamics simulations to analyze conformational preferences of
calcium-loaded CaM, initially in extended form. PRS is comprised of sequential
application of directed forces on residues followed by recording the resulting
coordinates. We show that manipulation of a single residue, E31 located in one
of the EF hand motifs, reproduces structural changes to compact forms, and the
flexible linker acts as a transducer of binding information to distant parts of
the protein. Independently, using four different pKa calculation strategies, we
find E31 to be the charged residue (out of 52), whose ionization state is most
sensitive to subtle pH variations in the physiological range. It is proposed
that at relatively low pH, CaM structure is less flexible. By gaining charged
states at specific sites at a pH value around 7, local conformational changes
in the protein will lead to shifts in the energy landscape, paving the way to
other conformational states. These findings are in accordance with FRET
measured shifts in conformational distributions towards more compact forms with
decreased pH. They also corroborate mutational studies and proteolysis results
which point to the significant role of E31 in CaM dynamics.Comment: 47 pages, 4 figure
Valley-spin blockade and spin resonance in carbon nanotubes
Manipulation and readout of spin qubits in quantum dots made in III-V
materials successfully rely on Pauli blockade that forbids transitions between
spin-triplet and spin-singlet states. Quantum dots in group IV materials have
the advantage of avoiding decoherence from the hyperfine interaction by
purifying them with only zero-spin nuclei. Complications of group IV materials
arise from the valley degeneracies in the electronic bandstructure. These lead
to complicated multiplet states even for two-electron quantum dots thereby
significantly weakening the selection rules for Pauli blockade. Only recently
have spin qubits been realized in silicon devices where the valley degeneracy
is lifted by strain and spatial confinement. In carbon nanotubes Pauli blockade
can be observed by lifting valley degeneracy through disorder. In clean
nanotubes, quantum dots have to be made ultra-small to obtain a large energy
difference between the relevant multiplet states. Here we report on
low-disorder nanotubes and demonstrate Pauli blockade based on both valley and
spin selection rules. We exploit the bandgap of the nanotube to obtain a large
level spacing and thereby a robust blockade. Single-electron spin resonance is
detected using the blockade.Comment: 31 pages including supplementary informatio
The role of CC chemokine receptor 5 (CCR5) and RANTES/CCL5 during chronic fungal asthma in mice1
In the present study, we explored the role of CC chemokine receptor 5 (CCR5) in a murine model of chronic fungal asthma induced by an intrapulmonary challenge with Aspergillus fumigatus conidia (or spores). Airway hyperresponsiveness was significantly lower in A. fumigatus‐sensitized mice lacking CCR5 (CCR5‐/‐) compared with similarly sensitized wild‐type (CCR5+/+) control mice at days 2, 21, 30, and 40 after the conidia challenge. CCR5‐/‐ mice exhibited significantly less peribronchial T‐cell and eosinophil accumulation and airway‐remodeling features, such as goblet cell hyperplasia and peribronchial fibrosis, compared with CCR5+/+ mice at these times after conidia. However, both groups of mice exhibited similar allergic airway disease at day 12 after the conidia challenge. In CCR5‐/‐ mice at day 12, the allergic airway disease was associated with airway hyperresponsiveness, peribronchial allergic inflammation, and goblet cell hyperplasia. Immunoneutralization of RANTES/CCL5 in sensitized CCR5+/+ and CCR5‐/‐ mice for 12 days after the conidia challenge significantly reduced the peribronchial inflammation and airway hyperresponsiveness in comparison with control wild‐type and knockout mice at this time. These data demonstrate that functional CCR5 and RANTES/CCL5 are required for the persistence of chronic fungal asthma in mice.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154329/1/fsb2fj010528fje.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154329/2/fsb2fj010528fje-sup-0001.pd
An addressable quantum dot qubit with fault-tolerant control fidelity
Exciting progress towards spin-based quantum computing has recently been made
with qubits realized using nitrogen-vacancy (N-V) centers in diamond and
phosphorus atoms in silicon, including the demonstration of long coherence
times made possible by the presence of spin-free isotopes of carbon and
silicon. However, despite promising single-atom nanotechnologies, there remain
substantial challenges in coupling such qubits and addressing them
individually. Conversely, lithographically defined quantum dots have an
exchange coupling that can be precisely engineered, but strong coupling to
noise has severely limited their dephasing times and control fidelities. Here
we combine the best aspects of both spin qubit schemes and demonstrate a
gate-addressable quantum dot qubit in isotopically engineered silicon with a
control fidelity of 99.6%, obtained via Clifford based randomized benchmarking
and consistent with that required for fault-tolerant quantum computing. This
qubit has orders of magnitude improved coherence times compared with other
quantum dot qubits, with T_2* = 120 mus and T_2 = 28 ms. By gate-voltage tuning
of the electron g*-factor, we can Stark shift the electron spin resonance (ESR)
frequency by more than 3000 times the 2.4 kHz ESR linewidth, providing a direct
path to large-scale arrays of addressable high-fidelity qubits that are
compatible with existing manufacturing technologies
Quantum control of hybrid nuclear-electronic qubits
Pulsed magnetic resonance is a wide-reaching technology allowing the quantum
state of electronic and nuclear spins to be controlled on the timescale of
nanoseconds and microseconds respectively. The time required to flip either
dilute electronic or nuclear spins is orders of magnitude shorter than their
decoherence times, leading to several schemes for quantum information
processing with spin qubits. We investigate instead the novel regime where the
eigenstates approximate 50:50 superpositions of the electronic and nuclear spin
states forming "hybrid nuclear-electronic" qubits. Here we demonstrate quantum
control of these states for the first time, using bismuth-doped silicon, in
just 32 ns: this is orders of magnitude faster than previous experiments where
pure nuclear states were used. The coherence times of our states are five
orders of magnitude longer, reaching 4 ms, and are limited by the
naturally-occurring 29Si nuclear spin impurities. There is quantitative
agreement between our experiments and no-free-parameter analytical theory for
the resonance positions, as well as their relative intensities and relative
Rabi oscillation frequencies. In experiments where the slow manipulation of
some of the qubits is the rate limiting step, quantum computations would
benefit from faster operation in the hybrid regime.Comment: 20 pages, 8 figures, new data and simulation
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