79 research outputs found
Protein kinase A–induced myofilament desensitization to Ca2+ as a result of phosphorylation of cardiac myosin–binding protein C
In skinned myocardium, cyclic AMP–dependent protein kinase A (PKA)-catalyzed phosphorylation of cardiac myosin–binding protein C (cMyBP-C) and cardiac troponin I (cTnI) is associated with a reduction in the Ca2+ responsiveness of myofilaments and an acceleration in the kinetics of cross-bridge cycling, although the respective contribution of these two proteins remains controversial. To further examine the relative roles that cTnI and cMyBP-C phosphorylation play in altering myocardial function, we determined the Ca2+ sensitivity of force (pCa50) and the activation dependence of the rate of force redevelopment (ktr) in control and PKA-treated mouse myocardium (isolated in the presence of 2,3-butanedione monoxime) expressing: (a) phosphorylatable cTnI and cMyBP-C (wild type [WT]), (b) phosphorylatable cTnI on a cMyBP-C–null background (cMyBP-C−/−), (c) nonphosphorylatable cTnI with serines23/24/43/45 and threonine144 mutated to alanines (cTnIAla5), and (d) nonphosphorylatable cTnI on a cMyBP-C–null background (cTnIAla5/cMyBP-C−/−). Here, PKA treatment decreased pCa50 in WT, cTnIAla5, and cMyBP-C−/− myocardium by 0.13, 0.08, and 0.09 pCa units, respectively, but had no effect in cTnIAla5/cMyBP-C−/− myocardium. In WT and cTnIAla5 myocardium, PKA treatment also increased ktr at submaximal levels of activation; however, PKA treatment did not have an effect on ktr in cMyBP-C−/− or cTnIAla5/cMyBP-C−/− myocardium. In addition, reconstitution of cTnIAla5/cMyBP-C−/− myocardium with recombinant cMyBP-C restored the effects of PKA treatment on pCa50 and ktr reported in cTnIAla5 myocardium. Collectively, these results indicate that the attenuation in myofilament force response to PKA occurs as a result of both cTnI and cMyBP-C phosphorylation, and that the reduction in pCa50 mediated by cMyBP-C phosphorylation most likely arises from an accelerated cross-bridge cycling kinetics partly as a result of an increased rate constant of cross-bridge detachment
Hybrid SPECT/CT for the assessment of a painful hip after uncemented total hip arthroplasty
Background The diagnosis of hip pain after total hip replacement (THR)
represents a highly challenging question that is of increasing concern to
orthopedic surgeons. This retrospective study assesses bone scintigraphy with
Hybrid SPECT/CT for the diagnosis of painful THR in a selected cohort of
patients. Methods Bone SPECT/CT datasets of 23 patients (mean age 68.9 years)
with a painful hip after THR were evaluated. Selection of the patients
required an inconclusive radiograph, normal serum levels of inflammatory
parameters (CRP and ESR) or a negative aspiration of the hip joint prior to
the examination. The standard of reference was established by an
interdisciplinary adjudication-panel using all imaging data and clinical
follow-up data (>12 month). Pathological and physiological uptake patterns
were defined and applied. Results The cause of pain in this study group could
be determined in 18 out of 23 cases. Reasons were aseptic loosening (n = 5),
spine-related (n = 5), heterotopic ossification (n = 5), neuronal (n = 1),
septic loosening (n = 1) and periprosthetic stress fracture (n = 1). In (n =
5) cases the cause of hip pain could not be identified. SPECT/CT imaging
correctly identified the cause of pain in (n = 13) cases, in which the
integrated CT-information led to the correct diagnosis in (n = 4) cases,
mainly through superior anatomic correlation. Loosening was correctly assessed
in all cases with a definite diagnosis. Conclusions SPECT/CT of THA reliably
detects or rules out loosening and provides valuable information about
heterotopic ossifications. Furthermore differential diagnoses may be detected
with a whole-body scan and mechanical or osseous failure is covered by CT-
imaging. SPECT/CT holds great potential for imaging-based assessment of
painful prostheses
Optical and structural properties of polycrystalline CVD diamond films grown on fused silica optical fibres pre-treated by high-power sonication seeding
A stature-specific concept for uncemented, primary total hip arthroplasty: 10-year results in 155 patients using two stem shapes and modular necks
Multi-messenger observations of a binary neutron star merger
On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta
The role of bovine preserved peritoneum in rats ventral hernia: a histological evaluation
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The Electromagnetic Counterpart of the Binary Neutron Star Merger LIGO/Virgo GW170817. II. UV, Optical, and Near-infrared Light Curves and Comparison to Kilonova Models
We present UV, optical, and NIR photometry of the first electromagnetic
counterpart to a gravitational wave source from Advanced LIGO/Virgo, the binary
neutron star merger GW170817. Our data set extends from the discovery of the
optical counterpart at days to days post-merger, and includes
observations with the Dark Energy Camera (DECam), Gemini-South/FLAMINGOS-2
(GS/F2), and the {\it Hubble Space Telescope} ({\it HST}). The spectral energy
distribution (SED) inferred from this photometry at days is well
described by a blackbody model with K, a radius of cm (corresponding to an expansion velocity of ), and a bolometric luminosity of erg
s. At days we find a multi-component SED across the optical and
NIR, and subsequently we observe rapid fading in the UV and blue optical bands
and significant reddening of the optical/NIR colors. Modeling the entire data
set we find that models with heating from radioactive decay of Ni, or
those with only a single component of opacity from -process elements, fail
to capture the rapid optical decline and red optical/NIR colors. Instead,
models with two components consistent with lanthanide-poor and lanthanide-rich
ejecta provide a good fit to the data, the resulting "blue" component has
M and
c, and the "red" component has
M and
c. These ejecta masses are broadly
consistent with the estimated -process production rate required to explain
the Milky Way -process abundances, providing the first evidence that BNS
mergers can be a dominant site of -process enrichment
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