Slowly cycling Rho kinase-dependent actomyosin cross-bridge slippage explains intrinsic high compliance of detrusor smooth muscle

Biological soft tissues are viscoelastic because they display timeindependent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+ -containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as slipping cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically

Measurement of the static Stark Shift of the 7s 2S1/27s \ ^2S_{1/2} level in atomic cesium

We report a new precision measurement of the dc Stark shift of the 6s\hspace{1mm} ^2S_{1/2} \rightarrow 7s\hspace{1mm}^2S_{1/2} transition in atomic cesium-133. Our result is 0.72246 (29) $\textrm{Hz}(\textrm{V}/\textrm{cm})^{-2}$. This result differs from a previous measurement of the Stark shift by $\sim$0.5\%. We use this value to recalculate the magnitude of the reduced dipole matrix elements $\langle7s ||r||7p_{j}\rangle$, as well as the vector transition polarizability for the $6s \rightarrow 7s$ transition, $\tilde{\beta} = 27.043 \: (36) \ a_0^3$. This determination helps resolve a critical discrepancy between two techniques for determining the vector polarizability.Comment: 5 pages, 3 figures, 3 table

Experience Improves the Reliability of Subjective Measurements of Temperament in Beef Cattle

Reliability of experienced and inexperienced observers when assessing the behavior of cattle when restrained in a squeeze chute (chute score), and when exiting the chute (exit score), was compared. Overall, experienced observers had higher reliability than inexperienced observers. Increasing the number of individuals scoring an animal decreased the degree of agreement. However, within an acceptable tolerance for difference in scores, such disagreement may be beneficial; it allows for subtlety in interpretations of temperament, which when averaged, may better reflect docility. Reliabilities were higher for exit score than chute score. This may reflect the complexity of the trait being evaluated, with fewer behaviors observed when cattle exit as compared to when restrained in a chute. Producers may profitably use chute and exit score to quantify docility in cattle. However, it may be worthwhile to gain experience in using the scoring system before implementing it for selection decisions

Experience Improves the Reliability of Subjective Measurements of Temperament in Beef Cattle

Reliability of experienced and inexperienced observers when assessing the behavior of cattle when restrained in a squeeze chute (chute score), and when exiting the chute (exit score), was compared. Overall, experienced observers had higher reliability than inexperienced observers. Increasing the number of individuals scoring an animal decreased the degree of agreement. However, within an acceptable tolerance for difference in scores, such disagreement may be beneficial; it allows for subtlety in interpretations of temperament, which when averaged, may better reflect docility. Reliabilities were higher for exit score than chute score. This may reflect the complexity of the trait being evaluated, with fewer behaviors observed when cattle exit as compared to when restrained in a chute. Producers may profitably use chute and exit score to quantify docility in cattle. However, it may be worthwhile to gain experience in using the scoring system before implementing it for selection decisions

Repeated Calm Handling Can Lead to More Docile Cattle

Changes in temperament in heifers when handled either frequently or infrequently were evaluated subjectively based on their behavior when restrained in (chute score) and exiting from (exit score) a squeeze chute. Chute scores decreased over time–a favorable direction–with more dramatic declines in heifers handled more frequently. Heifers with higher chute scores on the first day of handling had the largest reduction in score. Exit scores changed less over time. Chute score therefore may be more indicative of acclimation to a novel environment than exit score. Both scores appear to offer a fast, easy and inexpensive way to quantify docility in cattle. Heifers became calmer with repeated gentle handling. Producers therefore may benefit from allowing cattle a few days to acclimate to new working facilities before assessing docility

Presenting features and long-term effects of growth hormone treatment of children with optic nerve hypoplasia/septo-optic dysplasia

<p>Abstract</p> <p>Background</p> <p>Optic nerve hypoplasia (ONH) with/or without septo-optic dysplasia (SOD) is a known concomitant of congenital growth hormone deficiency (CGHD).</p> <p>Methods</p> <p>Demographic and longitudinal data from KIGS, the Pfizer International Growth Database, were compared between 395 subjects with ONH/SOD and CGHD and 158 controls with CGHD without midline pathology.</p> <p>Results</p> <p>ONH/SOD subjects had higher birth length/weight, and mid-parental height SDS. At GH start, height, weight, and BMI SDS were higher in the ONH/SOD group. After 1 year of GH, both groups showed similar changes in height SDS, while weight and BMI SDS remained higher in the ONH/SOD group. The initial height responses of the two groups were similar to those predicted using the KIGS-derived prediction model for children with idiopathic GHD. At near-adult height, ONH/SOD and controls had similar height, weight, and BMI SDS.</p> <p>Conclusions</p> <p>Compared to children with CGHD without midline defects, those with ONH/SOD presented with greater height, weight, and BMI SDS. These differences persisted at 1 year of GH therapy, but appeared to be overcome by long-term GH treatment.</p

Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease

Objective: To determine the motor phenotype of LRRK2 G2019S mutation carriers. LRRK2 mutation carriers were previously reported to manifest the tremor dominant motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared with the postural instability and gait difficulty (PIGD) phenotype. Design: Cross-sectional observational study. Setting: Thirteen movement disorders centers. Participants: Nine hundred twenty-five early-onset Parkinson disease cases defined as age at onset younger than 51 years. Main Outcome Measures: LRRK2 mutation status and Parkinson disease motor phenotype: tremor dominant or PIGD. Demographic information, family history of Parkinson disease, and the Unified Parkinson's Disease Rating Scale score were collected on all participants. DNA samples were genotyped for LRRK2 mutations (G2019S, I2020T, R1441C, and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish ancestry, levodopa dose, and family history of Parkinson disease. Results: Thirty-four cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be Ashkenazi Jewish (55.9% vs 11.9%; P < .001) but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (P = .03) and were more likely to have a PIGD phenotype (92.3% vs 58.9%; P = .003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and Ashkenazi Jewish ancestry (odds ratio, 17.7; P < .001). Conclusion: Early-onset Parkinson disease G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course

Pharmacogenetic Associations of MMP9 and MMP12 Variants with Cardiovascular Disease in Patients with Hypertension

MMP-9 and -12 function in tissue remodeling and may play roles in cardiovascular disease (CVD). We assessed associations of four MMP polymorphisms and three antihypertensive drugs with cardiovascular outcomes.Hypertensives (n = 42,418) from a double-blind, randomized, clinical trial were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatment (mean follow up, 4.9 years). The primary outcome was coronary heart disease (CHD). Secondary outcomes included combined CHD, all CVD outcomes combined, stroke, heart failure (HF), and mortality. Genotype-treatment interactions were tested. = 0.015). for CHD and composite CVD. The data suggest that these genes may provide useful clinical information with respect to treatment decisions