Regulated Inositol‐Requiring Protein 1‐Dependent Decay as a Mechanism of Corin RNA and Protein Deficiency in Advanced Human Systolic Heart Failure

BACKGROUND: The compensatory actions of the endogenous natriuretic peptide system require adequate processing of natriuretic peptide pro‐hormones into biologically active, carboxyl‐terminal fragments. Natriuretic peptide pro‐peptide processing is accomplished by corin, a transmembrane serine protease expressed by cardiomyocytes. Brain natriuretic peptide (BNP) processing is inadequate in advanced heart failure and is independently associated with adverse outcomes; however, the molecular mechanisms causing impaired BNP processing are not understood. We hypothesized that the development of endoplasmic reticulum stress in cardiomyocytes in advanced heart failure triggers inositol‐requiring protein 1 (IRE1)‐dependent corin mRNA decay, which would favor a molecular substrate favoring impaired natriuretic peptide pro‐peptide processing. METHODS AND RESULTS: Two independent samples of hearts obtained from patients with advanced heart failure at transplant demonstrated that corin RNA was reduced as Atrial natriuretic peptide (ANP)/BNP RNA increased. Increases in spliced X‐box protein 1, a marker for IRE1‐endoribonuclease activity, were associated with decreased corin RNA. Moreover, ≈50% of the hearts demonstrated significant reductions in corin RNA and protein as compared to the nonfailing control sample. In vitro experiments demonstrated that induction of endoplasmic reticulum stress in cultured cardiomyocytes with thapsigargin activated IRE1s endoribonuclease activity and time‐dependent reductions in corin mRNA. In HL‐1 cells, overexpression of IRE1 activated IRE1 endoribonuclease activity and caused corin mRNA decay, whereas IRE1‐RNA interference with shRNA attenuated corin mRNA decay after induction of endoplasmic reticulum stress with thapsigargin. Pre‐treatment of cells with Actinomycin D to inhibit transcription did not alter the magnitude or time course of thapsigargin‐induced corin mRNA decline, supporting the hypothesis that this was the result of IRE1‐mediated corin mRNA degradation. CONCLUSIONS: These data support the hypothesis that endoplasmic reticulum stress‐mediated, IRE1‐dependent targeted corin mRNA decay is a mechanism leading to corin mRNA resulting in corresponding corin protein deficiency may contribute to the pathophysiology of impaired natriuretic peptide pro‐hormone processing in humans processing in humans with advanced systolic heart failure

Postoperative complications associated with external skeletal fixators in cats

OBJECTIVES: The objective of this study was to quantify complications associated with external skeletal fixators (ESFs) in cats and to identify potential risk factors. METHODS: A retrospective review of medical records and radiographs following ESF placement was performed. RESULTS: Case records of 140 cats were reviewed; fixator-associated complications (FACs) occurred in 19% of cats. The region of ESF placement was significantly associated with complication development. Complications developed most frequently in the femur (50%), tarsus (35%) and radius/ulna (33%). Superficial pin tract infection (SPTI) and implant failure accounted for 45% and 41% of all FACs, respectively. SPTI occurred more frequently in the femur, humerus and tibia, with implant failure more frequent in the tarsus. No association between breed, age, sex, weight, fracture type (open vs closed), ESF classification, number of pins per bone segment, degree of fracture load sharing, and the incidence or type of FAC was identified. No association between region of placement, breed, age, sex, weight, fracture type (open vs closed), ESF classification, number of pins per bone segment, fracture load sharing and the time to complication development was identified. CONCLUSIONS AND RELEVANCE: Complication development is not uncommon in cats following ESF placement. The higher complication rate in the femur, tarsus and radius/ulna should be considered when reviewing options for fracture management. However, cats appear to have a lower rate of pin tract infections than dogs

Resonance Raman study of the A-band short-time photodissociation dynamics of axial and equatorial conformers of iodocyclopentane

We have obtained resonance Raman spectra of iodocyclopentane in cyclohexane solution at three excitation wavelengths resonant with the A-band absorption. The A-band resonance Raman spectral bands can be assigned to fundamentals, overtones, and combination bands of seven axial conformer and eight equatorial conformer Franck-Condon active modes. The resonance Raman and absorption cross sections were simultaneously simulated using wave packet calculations and a simple model. The best fit parameters of the simulations and the normal mode descriptions were used to determine the A-band short-time photodissociation dynamics of the axial and equatorial conformers of iodocyclopentane. The axial and equatorial conformers exhibit noticeably different short-time photodissociation dynamics that suggest that the C-I bond cleavage process is conformation dependent. The axial conformer short-time photodissociation dynamics have larger changes in the carbon-carbon stretch and three carbon atom bending motions as well as the torsional motion about the α and β carbon atom bond. The CCI bending motions for the axial and equatorial conformers of iodocyclopentane as well as previously reported results for the equatorial conformer of iodocyclohexane are significantly smaller than CCI bending motions found for most noncyclic iodoalkanes examined so far. This suggests that the cyclic backbone restricts the initial motion of the C-I bond cleavage along the CCI bend in iodocycloalkanes compared to the noncyclic iodoalkanes. © 1999 American Institute of Physics.published_or_final_versio

Changes in host muscles induced by excretory/secretory products of larval Trichinella spiralis and Trichinella pseudospiralis

Excretory/secretory (ES) products obtained by in vitro culture of infective-stage larvae of Trichinella spiralis and T. pseudospiralis were injected intramuscularly at various intervals into mice. Mini-osmotic pumps containing T. spiralis ES products were also implanted subcutaneously and intraperitoneally into rats. The introduction of ES materials into muscles elicited extensive lesions which included dissolution of myofibres, mobilization of mononuclear and polymorphonuclear leucocytes, angiogenesis, hypertrophy of myonuclei, myotube formation, mitosis, muscle bundles becoming rounded and separated from each other, disappearance of Z, I and A bands of sarcomeres, increase in endoplasmic reticulum and Golgi complexes, decrease in glycogen and relocation of mitochondria. These are considered as degenerative/regenerative changes of muscles to injury. Immunodominant epitopes of specific 45-53 kDa glycoproteins in ES antigens of T. spiralis could not be detected in hypertrophic nuclei of injected muscles by using polyclonal and monoclonal antibodies and immunocytochemical methods. ES products of T. spiralis failed to stimulate unsensitized lymphocytes in the lymphocyte transformation test. Infective-stage larvae of T. spiralis released from muscles were found capable of forming nurse cells after injection subcutaneously into rats. It is postulated that the invasion of muscles by trichinellids elicits two independent events, i.e. a general degenerative/regenerative response of muscles and a specific change in genomic expression of myonuclei. The two events are probably mediated by different effector molecules.published_or_final_versio

A multicentre comparison of quantitative 90Y PET/CT for dosimetric purposes after radioembolization with resin microspheres

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Peer review and citation data in predicting university rankings, a large-scale analysis

Most Performance-based Research Funding Systems (PRFS) draw on peer review and bibliometric indicators, two different method- ologies which are sometimes combined. A common argument against the use of indicators in such research evaluation exercises is their low corre- lation at the article level with peer review judgments. In this study, we analyse 191,000 papers from 154 higher education institutes which were peer reviewed in a national research evaluation exercise. We combine these data with 6.95 million citations to the original papers. We show that when citation-based indicators are applied at the institutional or departmental level, rather than at the level of individual papers, surpris- ingly large correlations with peer review judgments can be observed, up to r <= 0.802, n = 37, p < 0.001 for some disciplines. In our evaluation of ranking prediction performance based on citation data, we show we can reduce the mean rank prediction error by 25% compared to previous work. This suggests that citation-based indicators are sufficiently aligned with peer review results at the institutional level to be used to lessen the overall burden of peer review on national evaluation exercises leading to considerable cost savings

Spin-lattice instability to a fractional magnetization state in the spinel HgCr2O4

Magnetic systems are fertile ground for the emergence of exotic states when the magnetic interactions cannot be satisfied simultaneously due to the topology of the lattice - a situation known as geometrical frustration. Spinels, AB2O4, can realize the most highly frustrated network of corner-sharing tetrahedra. Several novel states have been discovered in spinels, such as composite spin clusters and novel charge-ordered states. Here we use neutron and synchrotron X-ray scattering to characterize the fractional magnetization state of HgCr2O4 under an external magnetic field, H. When the field is applied in its Neel ground state, a phase transition occurs at H ~ 10 Tesla at which each tetrahedron changes from a canted Neel state to a fractional spin state with the total spin, Stet, of S/2 and the lattice undergoes orthorhombic to cubic symmetry change. Our results provide the microscopic one-to-one correspondence between the spin state and the lattice distortion

Transient resonance Raman spectroscopy and density functional theory investigation of iso-CHBr 2Cl and iso-CCl 3Br photoproducts produced following ultraviolet excitation of CHBr 2Cl and CCl 3Br

Two polyhalomethanes that contain bromine and chlorine atoms (CHBr 2Cl and CCl 2Br) were studied. Transient resonance Raman spectra were obtained for the photoproducts produced after ultraviolet excitation of CHBr 2Cl and CCl 3Br in room temperature solutions and density functional theory calculations for species proposed to be products of the photodissociation reactions in the solution phase. It was found that the iso-CHBrCl-Br and iso-CHClBr-Br species are formed following ultraviolet excitation of CHBr 2Cl and the iso-CCl 2Cl-Br species formed following ultraviolet excitation of CCl 3Br in the solution phase.published_or_final_versio

Unhealthy weight control behaviours in adolescent girls: a process model based on self-determination theory

This study used self-determination theory (Deci, E.L., & Ryan, R.M. (2000). The 'what' and 'why' of goal pursuits: Human needs and the self-determination of behavior. Psychological Inquiry, 11, 227-268.) to examine predictors of body image concerns and unhealthy weight control behaviours in a sample of 350 Greek adolescent girls. A process model was tested which proposed that perceptions of parental autonomy support and two life goals (health and image) would predict adolescents' degree of satisfaction of their basic psychological needs. In turn, psychological need satisfaction was hypothesised to negatively predict body image concerns (i.e. drive for thinness and body dissatisfaction) and, indirectly, unhealthy weight control behaviours. The predictions of the model were largely supported indicating that parental autonomy support and adaptive life goals can indirectly impact upon the extent to which female adolescents engage in unhealthy weight control behaviours via facilitating the latter's psychological need satisfaction