In vivo inhibition of TRPC6 by SH045 attenuates renal fibrosis in a New Zealand Obese (NZO) mouse model of metabolic syndrome

Metabolic syndrome is a significant worldwide public health challenge and is inextricably linked to adverse renal and cardiovascular outcomes. The inhibition of the transient receptor potential cation channel subfamily C member 6 (TRPC6) has been found to ameliorate renal outcomes in the unilateral ureteral obstruction (UUO) of accelerated renal fibrosis. Therefore, the pharmacological inhibition of TPRC6 could be a promising therapeutic intervention in the progressive tubulo-interstitial fibrosis in hypertension and metabolic syndrome. In the present study, we hypothesized that the novel selective TRPC6 inhibitor SH045 (larixyl N-methylcarbamate) ameliorates UUO-accelerated renal fibrosis in a New Zealand obese (NZO) mouse model, which is a polygenic model of metabolic syndrome. The in vivo inhibition of TRPC6 by SH045 markedly decreased the mRNA expression of pro-fibrotic markers (Col1α1, Col3α1, Col4α1, Acta2, Ccn2, Fn1) and chemokines (Cxcl1, Ccl5, Ccr2) in UUO kidneys of NZO mice compared to kidneys of vehicle-treated animals. Renal expressions of intercellular adhesion molecule 1 (ICAM-1) and α-smooth muscle actin (α-SMA) were diminished in SH045- versus vehicle-treated UUO mice. Furthermore, renal inflammatory cell infiltration (F4/80+ and CD4+) and tubulointerstitial fibrosis (Sirius red and fibronectin staining) were ameliorated in SH045-treated NZO mice. We conclude that the pharmacological inhibition of TRPC6 might be a promising antifibrotic therapeutic method to treat progressive tubulo-interstitial fibrosis in hypertension and metabolic syndrome

Semidiscrete biomass dynamic modeling: an improved approach for assessing fish stock responses to pulsed harvest events

Continuous harvest over an annual period is a common assumption of continuous biomass dynamics models (CBDMs); however, fish are frequently harvested in a discrete manner. We developed semidiscrete biomass dynamics models (SDBDMs) that allow discrete harvest events and evaluated differences between CBDMs and SDBDMs using an equilibrium yield analysis with varying levels of fishing mortality (F). Equilibrium fishery yields for CBDMs and SDBDMS were similar at low fishing mortalities and diverged as F approached and exceeded maximum sustained yield (FMSY). Discrete harvest resulted in lower equilibrium yields at high levels of Frelative to continuous harvest. The effect of applying harvest continuously when it was in fact discrete was evaluated by fitting CBDMs and SDBDMs to time series data generated from a hypothetical fish stock undergoing discrete harvest and evaluating parameter estimates bias. Violating the assumption of continuous harvest resulted in biased parameter estimates for CBDM while SDBDM parameter estimates were unbiased. Biased parameter estimates resulted in biased biological reference points derived from CBDMs. Semidiscrete BDMs outperformed continuous BDMs and should be used when harvest is discrete, when the time and magnitude of harvest are known, and when F is greater than FMSY.This article is from Canadian Journal of Fisheries and Aquatic Sciences 69 (2012): 1710, doi:10.1139/f2012-084.</p

Decomposition of operator semigroups on W*-algebras

We consider semigroups of operators on a W$^*$-algebra and prove, under appropriate assumptions, the existence of a Jacobs-DeLeeuw-Glicksberg type decomposition. This decomposition splits the algebra into a "stable" and "reversible" part with respect to the semigroup and yields, among others, a structural approach to the Perron-Frobenius spectral theory for completely positive operators on W$^*$-algebras.Comment: referee's comments incorporated. To appear in Semigroup Foru

Gravitational radiation from gamma-ray bursts as observational opportunities for LIGO and VIRGO

Gamma-ray bursts are believed to originate in core-collapse of massive stars. This produces an active nucleus containing a rapidly rotating Kerr black hole surrounded by a uniformly magnetized torus represented by two counter-oriented current rings. We quantify black hole spin-interactions with the torus and charged particles along open magnetic flux-tubes subtended by the event horizon. A major output of Egw=4e53 erg is radiated in gravitational waves of frequency fgw=500 Hz by a quadrupole mass-moment in the torus. Consistent with GRB-SNe, we find (i) Ts=90s (tens of s, Kouveliotou et al. 1993), (ii) aspherical SNe of kinetic energy Esn=2e51 erg (2e51 erg in SN1998bw, Hoeflich et al. 1999) and (iii) GRB-energies Egamma=2e50 erg (3e50erg in Frail et al. 2001). GRB-SNe occur perhaps about once a year within D=100Mpc. Correlating LIGO/Virgo detectors enables searches for nearby events and their spectral closure density 6e-9 around 250Hz in the stochastic background radiation in gravitational waves. At current sensitivity, LIGO-Hanford may place an upper bound around 150MSolar in GRB030329. Detection of Egw thus provides a method for identifying Kerr black holes by calorimetry.Comment: to appear in PRD, 49

Role of TRPC6 in kidney damage after acute ischemic kidney injury

Transient receptor potential channel subfamily C, member 6 (TRPC6), a non-selective cation channel that controls influx of Ca(2+) and other monovalent cations into cells, is widely expressed in the kidney. TRPC6 gene variations have been linked to chronic kidney disease but its role in acute kidney injury (AKI) is unknown. Here we aimed to investigate the putative role of TRPC6 channels in AKI. We used Trpc6(-/-) mice and pharmacological blockade (SH045 and BI-749327), to evaluate short-term AKI outcomes. Here, we demonstrate that neither Trpc6 deficiency nor pharmacological inhibition of TRPC6 influences the short-term outcomes of AKI. Serum markers, renal expression of epithelial damage markers, tubular injury, and renal inflammatory response assessed by the histological analysis were similar in wild-type mice compared to Trpc6(-/-) mice as well as in vehicle-treated versus SH045- or BI-749327-treated mice. In addition, we also found no effect of TRPC6 modulation on renal arterial myogenic tone by using blockers to perfuse isolated kidneys. Therefore, we conclude that TRPC6 does not play a role in the acute phase of AKI. Our results may have clinical implications for safety and health of humans with TRPC6 gene variations, with respect to mutated TRPC6 channels in the response of the kidney to acute ischemic stimuli

The SAMI Galaxy Survey: Spatially resolving the environmental quenching of star formation in GAMA galaxies

We use data from the Sydney-AAO Multi-Object Integral Field Spectrograph (SAMI) Galaxy Survey and the Galaxy And Mass Assembly (GAMA) survey to investigate the spatially-resolved signatures of the environmental quenching of star formation in galaxies. Using dust-corrected measurements of the distribution of Hα emission we measure the radial profiles of star formation in a sample of 201 star-forming galaxies covering three orders of magnitude in stellar mass (M∗M∗; 108.1-1010.95 M⊙) and in 5th nearest neighbour local environment density (Σ5; 10−1.3- 102.1 Mpc−2). We show that star formation rate gradients in galaxies are steeper in dense (log10(Σ5/Mpc2) > 0.5) environments by 0.58 ± 0.29 dex re−1 in galaxies with stellar masses in the range 1010 1.0). These lines of evidence strongly suggest that with increasing local environment density the star formation in galaxies is suppressed, and that this starts in their outskirts such that quenching occurs in an outside-in fashion in dense environments and is not instantaneous

Transcatheter aortic valve implantation in failed bioprosthetic surgical valves.

IMPORTANCE: Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed. OBJECTIVE: To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves. DESIGN, SETTING, AND PARTICIPANTS: Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 [SD, 9.8] years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% [interquartile range, 7.7%-16%]). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (&gt;21 and &lt;25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves. MAIN OUTCOMES AND MEASURES: Survival, stroke, and New York Heart Association functional class. RESULTS: Modes of bioprosthesis failure were stenosis (n = 181 [39.4%]), regurgitation (n = 139 [30.3%]), and combined (n = 139 [30.3%]). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% [95% CI, 66.2%-83.4%]; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008). CONCLUSIONS AND RELEVANCE: In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis

Surface effects in nucleation and growth of smectic B crystals in thin samples

We present an experimental study of the surface effects (interactions with the container walls) during the nucleation and growth of smectic B crystals from the nematic in free growth and directional solidification of a mesogenic molecule ($C_4H_9-(C_6H_{10})_2CN$) called CCH4 in thin (of thickness in the 10 $\mu$m range) samples. We follow the dynamics of the system in real time with a polarizing microscope. The inner surfaces of the glass-plate samples are coated with polymeric films, either rubbed polyimid (PI) films or monooriented poly(tetrafluoroethylene) (PTFE) films deposited by friction at high temperature. The orientation of the nematic and the smectic B is planar. In PI-coated samples, the orientation effect of SmB crystals is mediated by the nematic, whereas, in PTFE-coated samples, it results from a homoepitaxy phenomenon occurring for two degenerate orientations. A recrystallization phenomenon partly destroys the initial distribution of crystal orientations. In directional solidification of polycrystals in PTFE-coated samples, a particular dynamics of faceted grain boundary grooves is at the origin of a dynamical mechanism of grain selection. Surface effects also are responsible for the nucleation of misoriented terraces on facets and the generation of lattice defects in the solid.Comment: 15 pages, 24 figures, submitted to PR

New way of healing : experienced counsellors’ perceptions of the influence of ch’i-related exercises on counselling practice in Taiwan

This study examines how Taiwanese senior counsellors with substantial experience of ch’i-related exercise (CRE) perceived the influence of their regular CRE on their counselling practice. I am interested in the perceived influence of CRE on both self-care and professional practice. In this studyn this studyn this study n this study n this study n this study, CRE, CRE, CRE, CRE, CRE refers to any refers to any refers to any refers to any ch'i enhancing exercise that coordinates movement with breathing and inner concentration wherein ch'i is a first order concept used by practitioners and regarded by them as an embodiment of ideas related to human life and human existence and able to be experienced and refined through any ch'i related exercise. CRE is a set of practices and an intrinsic part of local culture in Taiwan which in recent years, has become popular practice in Taiwanese society. There are growing numbers of counselling professionals involved in regular CRE in recent years. Studies examining the effects of CRE indicate the benefits of CRE on practitioners' global health and personal growth. However, no previous study has investigated the influence of the long-term regular use of CRE on counsellors‟ self-care and counselling practice. The narrative research design for this study was developed from a post-structural theoretical perspective located in the domain of social constructivism. The data were co-constructed between the researcher and 12 senior Taiwanese counsellors with substantial CRE experience using a semi-structured in-depth interview approach. Interview data were analysed using the structure-based approach developed by William Labov in the field of socio-linguistics. The study reveals an overall benefit of regular involvement in CRE for practitioners' global wellbeing and personal growth counsellor' self-care. The research findings also reveals the potential of ch’i to be used as a way of expressing health and illness and a way of understanding in therapy and CRE to be lived out in therapy as an embodiment. I argue that collectively the narratives, as a whole, give evidence of an increasing integratin of the ideas and practices of ch’i into counselling practice in contemporary Taiwan. This might even make up a new form of integrated and culturally appropriate practice, what I term "a new way of healing." These are therapeutic practices which value the potential of CRE for counsellor's self-care and personal growth; recognize the integral whole of the human person; promote conscious use of the knowledge and experience of ch’i and CRE in therapy as an important aspect of the therapeutic use of self. Implications for practice such as the potential of CRE to be introduced into counsellor training programmes for counsellors' preparation or ongoing education are provided. Recommendations for future research such as the development of a new healing modality based on the research findings are offered