Effect of Microgravity on the Contraction and Cytoskeletal Remodeling of A7r5 Smooth Muscle Cells

Smooth muscle presents several unique contractile properties when compared to striated muscle. Data suggests that differential remodeling of the alpha-actin and beta-actin and the regulation of such remodeling may play an essential role in smooth muscle contraction. At rest both alpha- and beta-actin both exhibit a cable-like appearance. During contraction, alpha-actin appears to undergo significant remodeling with dissolution on the majority of the cables and the formation of podosomes where it demonstrates co-localization with myosin while beta-actin retains a cable-like appearance. While the remodeling of the two actin domains has been characterized under normal gravity little is known regarding cytoskeletal dynamics in A7r5 smooth muscle cells. A7r5 cells will be subjected to the microgravity environment of the International Space Station. We speculate that the absence of gravity as an organizing force on biological structures may produce different effects than what is observed on Earth. In collaboration with SpaceTango Inc., a cell culturing module has been engineered that will allow the cells to ascend into space and maintain homeostasis while on orbit. The module will also administer phorbol ester, a contractile stimulant, followed by acetone to “fix” the cells in their contracted state so observations can be made about the aforementioned processes when they return from orbit

FUNCTION AND STRENGTH OF PHYSICALLY ACTIVE INDIVIDUALS WITH A UNILATERAL, SINGLE-AXIS KNEE REPLACEMENT

INTRODUCTION: Only recently could total knee replacement (TKR) individuals participate in many activities that place high stress on the knee region, e.g., golf. To enhance physical functioning, TKR components must be able to provide optimal leverage for the quadriceps to generate extensor torque, a-p stability when the cruciate ligaments are sacrificed, and varusvalgus stability via adequate medial and lateral collateral tension throughout the (Range of Motion) ROM. The use of a single flexion/extension (F/E) axis TKR design rather than a multiaxial TKR design has been theorized to accomplish these goals. Therefore, for this work in progress, it was of interest to determine for physically active individuals if the strength and function of the limb with a unilateral, single-axis TKR would be different to that of the intact limb

Methods for Assessing Child and Family Outcomes in Early Childhood Special Education Programs

Although many concerns have been raised about methods of assessing outcomes in early childhood special education programs, professionals in the field are nevertheless faced with the need to select appropriate instruments for evaluating child and family outcomes as the result of intervention. A conference to address the current assessment needs of professionals was convened. This paper summarizes this conference, in which five prominent individuals in the field of early childhood special education gave specific recommendations for one child and one family outcome measure which would be applicable to a range of handicapped children between birth and age 5 being served in typical early intervention programs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68510/2/10.1177_027112148600600202.pd

A Meta-Analysis and Genome-Wide Association Study of Platelet Count and Mean Platelet Volume in African Americans

Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p<5×10−8 of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value): 6p22 (rs12526480, LRRC16A, p = 9.1×10−9), 7q11 (rs13236689, CD36, p = 2.8×10−9), 10q21 (rs7896518, JMJD1C, p = 2.3×10−12), 11q13 (rs477895, BAD, p = 4.9×10−8), and 20q13 (rs151361, SLMO2, p = 9.4×10−9). Three of these loci (10q21, 11q13, and 20q13) were replicated in European Americans (N = 14,909) and one (11q13) in Hispanic Americans (N = 3,462). For MPV (N = 4,531), genetic variants in 3 regions were significant at p<5×10−8, two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24). Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic groups. In addition, we also found one region associated with platelet aggregation that may play a potential role in atherothrombosis

Food restriction reduces sympathetic support of blood pressure in spontaneously hypertensive rats

We tested the hypothesis that food restriction would attenuate the development of hypertension in spontaneously hypertensive rats (SHR). Furthermore, we hypothesized that food restriction would reduce the tonic sympathetic nervous system support of blood pressure in the SHR. Male SHR (Charles River, age 5 wk) were randomly assigned to ad libitum (ADLIB, n = 8) or food-restricted (FR, n = 9) groups. ADLIB rats were given free access to nonpurified diet and demineralized water. Food-restricted rats ate 60% of the amount of nonpurified diet consumed by rats in the ADLIB group. After 8 wk of treatment, ADLIB rats were heavier than FR rats (ADLIB = 318 ± 4 g; FR = 193 ± 5 g, P \u3c 0.05). Blood pressure and heart rate (HR) were measured after chronic implantation of iliac arterial and jugular venous catheters. Food-restricted rats had lower mean arterial blood pressure (MAP) than ADLIB rats, measured in conscious, unrestrained state 4–6 h after catheterization (ADLIB = 162 ± 3 mmHg; FR = 142 ± 3 mmHg, P \u3c 0.05) and measured on the day after surgery (ADLIB = 150 ± 6 mmHg; FR = 130 ± 3 mmHg, P \u3c 0.05). There were no significant differences in resting HR on either day. Food-restricted rats exhibited augmented cardiac baroreflex-mediated bradycardia (bolus phenylephrine, 0.5–4.0 μg/kg intravenously) as assessed by linear slope of the ΔHR/ΔMAP relationship (ADLIB = −0.73 beats/(min⋅mmHg); FR = −1.62 beats/(min⋅mmHg), P \u3c 0.05). Sympathetic support of blood pressure quantified by the depressor response to ganglionic blockade (hexamethonium 30 mg/kg; atropine 0.1 mg/kg intravenously), was greater in the ADLIB group (ADLIB: −59 ± 8 mmHg; FR: −36 ± 2 mmHg, P \u3c 0.05). The results support the hypotheses that chronic food restriction reduces the development of hypertension and sympathetic support of MAP in spontaneously hypertensive rats

Food restriction reduces sympathetic support of blood pressure in spontaneously hypertensive rats

We tested the hypothesis that food restriction would attenuate the development of hypertension in spontaneously hypertensive rats (SHR). Furthermore, we hypothesized that food restriction would reduce the tonic sympathetic nervous system support of blood pressure in the SHR. Male SHR (Charles River, age 5 wk) were randomly assigned to ad libitum (ADLIB, n = 8) or food-restricted (FR, n = 9) groups. ADLIB rats were given free access to nonpurified diet and demineralized water. Food-restricted rats ate 60% of the amount of nonpurified diet consumed by rats in the ADLIB group. After 8 wk of treatment, ADLIB rats were heavier than FR rats (ADLIB = 318 ± 4 g; FR = 193 ± 5 g, P \u3c 0.05). Blood pressure and heart rate (HR) were measured after chronic implantation of iliac arterial and jugular venous catheters. Food-restricted rats had lower mean arterial blood pressure (MAP) than ADLIB rats, measured in conscious, unrestrained state 4–6 h after catheterization (ADLIB = 162 ± 3 mmHg; FR = 142 ± 3 mmHg, P \u3c 0.05) and measured on the day after surgery (ADLIB = 150 ± 6 mmHg; FR = 130 ± 3 mmHg, P \u3c 0.05). There were no significant differences in resting HR on either day. Food-restricted rats exhibited augmented cardiac baroreflex-mediated bradycardia (bolus phenylephrine, 0.5–4.0 μg/kg intravenously) as assessed by linear slope of the ΔHR/ΔMAP relationship (ADLIB = −0.73 beats/(min⋅mmHg); FR = −1.62 beats/(min⋅mmHg), P \u3c 0.05). Sympathetic support of blood pressure quantified by the depressor response to ganglionic blockade (hexamethonium 30 mg/kg; atropine 0.1 mg/kg intravenously), was greater in the ADLIB group (ADLIB: −59 ± 8 mmHg; FR: −36 ± 2 mmHg, P \u3c 0.05). The results support the hypotheses that chronic food restriction reduces the development of hypertension and sympathetic support of MAP in spontaneously hypertensive rats

Food restriction lowers sympathetic support of blood pressure in aortic coarctation hypertension

The purpose of this study was to examine the effects of short-term food restriction on the development of aortic coarctation (AC)-induced hypertension. PC hypertension was induced in female Sprague-Dawley rats (251 ±6 g) by placing a suprarenal constricting ligature around the abdominal aorta using a blunt 21 gauge needle as a guide. Four days following AC, rats were assigned to an ad libitum fed (ADLIB; n=4) or food restricted (FR; n=5) group. FR rats received 60% of the food consumed by ADLIB rats. Following three weeks of food restriction, FR rats had significantly lower body weight (184 ±5 vs. 265 ± 5 g). Carotid and jugular catheters were implanted under halothane anaesthesia for measurement of pulsatile blood pressure and infusion of drugs in conscious rats. Food restriction resulted in a reduction in resting mean arterial pressure (145 ±9 vs. 177 ±14 mmHg), systolic blood pressure (163 ±11 vs. 213 ±22 rrmHg), diastolic blood pressure (127 ±9 vs. 147 ±9 mmHg), and heart rate (377 ±16 vs. 406 ±10 bpm) compared to ADLIB rats. There was also an attenuated depressor response to ganglionic blockade (hexamethoniunVatropine, i.V.) in FR animals (-51 ±6 vs. -88 ±5 mmHg). The cardiovascular responsiveness to graded doses of the alpha receptor agonist phenylephrine (in the ganglionic blocked rat) was not different between groups. The résulte indicate that 3 weeks of food restriction (60% of ADUB) significantly attenuates the rise in blood pressure following AC, and is accompanied by a decrease in sympathetic nervous system support of blood pressure. JMV is a Graduate Student Research Fellow, Amer. Heart Assoc., FL Affiliate