Substituted indanylacetic acids as PPAR-alpha-gamma activators

A series of oxazole-substituted indanylacetic acids were prepared which show a spectrum of activity as ligands for PPAR nuclear receptor subtypes.     

An investigation into the acute effects of depth jumps on maximal strength performance

Research has demonstrated that high-load low-velocity (HLLV) exercises (≥85% 1 repetition maximum [1RM]) increase performance in subsequent low-load high-velocity (LLHV) exercises, when separated by a rest period ≥4 minutes. To date, few studies have investigated LLHV exercises on subsequent HLLV exercises. The purpose of this study was to compare the effects of 2, 4, or 6 depth jumps (DJs) on subsequent 1RM back squat performance. Fourteen subjects (age 22 ± 4 years, height 177 ± 10 cm, body mass 80.3 ± 14.4 kg) completed five 1RM back squat testing sessions, either control, retest, or 1 of 3 interventions (2, 4, or 6 DJs from a height of 33 cm, 4 minutes before the first 1RM attempt), in a counterbalanced order. Intraclass correlation coefficients demonstrated a high test-retest reliability for the 1RMs (r = 0.989, p < 0.001). Repeated-measures analysis of variance with Bonferroni post hoc analysis revealed significantly greater 1RM performance (140.71 ± 35.68 kg: p = 0.004, 140.50 ± 33.77 kg: p < 0.001, 141.43 ± 34.39 kg: p = 0.002, respectively) for each intervention (2, 4, or 6 repetitions, respectively) compared to the control condition (132.43 ± 34.56 kg). No significant differences were found between interventions (p > 0.05). The findings of this investigation demonstrate that the inclusion of 2, 4, or 6 DJs, 4 minutes before a maximal squat, enhances subsequent strength performance.     

Effects of sex,size and substrate on growth and mortality of trees in tropical wet forest

Summary Females and males of three tree species did not differ in growth or mortality over an interval of 9.5 years. Comparing between sexes and across species, there was no consistent pattern of effects of short-term (1 year) growth and fecundity on longer-term gorwth or mortality. Effects of size were significant (but minor) for growth in one species, and were significant for mortality in two species. Soil type affected mortality in one species, but affected growth in all three species. Sex and size are not consistently strong bases for predicting the performance of adult trees.     

A comparison of maximal squat strength and 5-, 10-, and 20-meter sprint times, in athletes and recreationally trained men

The purpose of this study was to identify whether there was a relationship between relative strength during a 1 repetition maximum (1RM) back squat and 5-, 10-, and 20-m sprint performances in both trained athletes and recreationally trained individuals. Professional rugby league players (n = 24) and recreationally trained individuals (n = 20) participated in this investigation. Twenty-meter sprint time and 1RM back squat strength, using free weights, were assessed on different days. There were no significant (p ≥ 0.05) differences between the well-trained and recreationally trained groups for 5-m sprint times. In contrast, the well-trained group's 10- and 20-m sprint times were significantly quicker (p = 0.004; p = 0.002) (1.78 + 0.06 seconds; 3.03 + 0.09 seconds) compared with the recreationally trained group (1.84 + 0.07 seconds; 3.13 + 0.11 seconds). The athletes were significantly stronger (170.63 + 21.43 kg) than the recreationally trained individuals (135.45 + 30.07 kg) (p = 0.01); however, there were no significant differences (p > 0.05) in relative strength between groups (1.78 + 0.27 kg/kg; 1.78 + 0.33 kg/kg, respectively). Significant negative correlations were found between 5-m sprint time and relative squat strength (r = -0.613, power = 0.96, p = 0.004) and between relative squat strength and 10- and 20-m sprint times in the recreationally trained group (r = -0.621, power = 0.51, p = 0.003; r = -0.604, power = 0.53, p = 0.005, respectively). These results, indicating that relative strength, are important for initial sprint acceleration in all athletes but more strongly related to sprint performance over greater distances in recreationally trained individuals.     

Shedding light on plant competition: modelling the influence of plant morphology on light capture (and vice versa)

A plant's morphology is both strongly influenced by local light availability and, simultaneously, strongly influences this local light availability. This reciprocal relationship is complex, but lies at the heart of understanding plant growth and competition. Here, we develop a sub-individual-based simulation model, cast at the level of interacting plant components. The model explicitly simulates growth, development and competition for light at the level of leaves, branches, etc., located in 3D space. In this way, we are able to explore the manner in which the low-level processes governing plant growth and development give rise to individual-, cohort-, and community-level phenomena. In particular, we show that individual-level trade-offs between growing up and growing out arise naturally in the model, and robustly give rise to cohort-level phenomena such as self-thinning, and community processes such as the effect of ecological disturbance on the maintenance of biodiversity. We conclude with a note on our methodology and how to interpret the results of simulation models such as this one.     

Postproduction Processing of Electrospun Fibres for Tissue Engineering

Electrospinning is a commonly used and versatile method to produce scaffolds (often biodegradable) for 3D tissue engineering.^{1, 2, 3} Many tissues in vivo undergo biaxial distension to varying extents such as skin, bladder, pelvic floor and even the hard palate as children grow. In producing scaffolds for these purposes there is a need to develop scaffolds of appropriate biomechanical properties (whether achieved without or with cells) and which are sterile for clinical use. The focus of this paper is not how to establish basic electrospinning parameters (as there is extensive literature on electrospinning) but on how to modify spun scaffolds post production to make them fit for tissue engineering purposes - here thickness, mechanical properties and sterilisation (required for clinical use) are considered and we also describe how cells can be cultured on scaffolds and subjected to biaxial strain to condition them for specific applications.Electrospinning tends to produce thin sheets; as the electrospinning collector becomes coated with insulating fibres it becomes a poor conductor such that fibres no longer deposit on it. Hence we describe approaches to produce thicker structures by heat or vapour annealing increasing the strength of scaffolds but not necessarily the elasticity. Sequential spinning of scaffolds of different polymers to achieve complex scaffolds is also described. Sterilisation methodologies can adversely affect strength and elasticity of scaffolds. We compare three methods for their effects on the biomechanical properties on electrospun scaffolds of poly lactic-co-glycolic acid (PLGA).Imaging of cells on scaffolds and assessment of production of extracellular matrix (ECM) proteins by cells on scaffolds is described. Culturing cells on scaffolds in vitro can improve scaffold strength and elasticity but the tissue engineering literature shows that cells often fail to produce appropriate ECM when cultured under static conditions. There are few commercial systems available that allow one to culture cells on scaffolds under dynamic conditioning regimes - one example is the Bose Electroforce 3100 which can be used to exert a conditioning programme on cells in scaffolds held using mechanical grips within a media filled chamber.⁴ An approach to a budget cell culture bioreactor for controlled distortion in 2 dimensions is described. We show that cells can be induced to produce elastin under these conditions. Finally assessment of the biomechanical properties of processed scaffolds cultured with or without cells is described.     

Induction of CD70 on dendritic cells through CD40 or TLR stimulation contributes to the development of CD8+ T cell responses in the absence of CD4+ T cells

The expansion of CD8(+) T cells in response to Ag can be characterized as either dependent or independent of CD4(+) T cells. The factors that influence this dichotomy are poorly understood but may be dependent upon the degree of inflammation associated with the Ag. Using dendritic cells derived from MHC class II-deficient mice to avoid interaction with CD4(+) T cells in vivo, we have compared the immunogenicity of peptide-pulsed dendritic cells stimulated with molecules associated with infection to those stimulated via CD40. In the absence of CD4(+) T cell help, the expansion of primary CD8(+) T cells after immunization with TNF-alpha- or poly(I:C)-stimulated dendritic cells was minimal. In comparison, LPS- or CpG-stimulated dendritic cells elicited substantial primary CD8(+) T cell responses, though not to the same magnitude generated by immunization with CD40L-stimulated dendritic cells. Remarkably, mice immunized with any stimulated dendritic cell population generated fully functional recall CD8(+) T cells without the aid of CD4(+) T cell help. The observed hierarchy of immunogenicity was closely correlated with the expression of CD70 (CD27L) on the stimulated dendritic cells, and Ab-mediated blockade of CD70 substantially prevented the CD4(+) T cell-independent expansion of primary CD8(+) T cells. These results indicate that the expression of CD70 on dendritic cells is an important determinant for helper-dependence of primary CD8(+) T cell expansion and provide an explanation for the ability of a variety of pathogens to stimulate primary CD8(+) T cell responses in the absence of CD4(+) T cells.     

Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin

The effects of feeding cholesterol, sitosterol, and lovastatin on cholesterol absorption, biosynthesis, esterification, and LDL receptor function were examined in the rat jejunal mucosa. Cholesterol absorption was measured by the dual-isotope plasma ratio method; the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, was measured as total and expressed enzyme activities (in the absence and presence of a phosphatase inhibitor, NaF, respectively); mucosal total and esterified cholesterol concentrations were determined by gas-liquid chromatography; LDL receptor function was assayed as receptor-mediated binding of (125)I-labeled LDL to mucosal membranes. Feeding 2% sitosterol or 0.04% lovastatin for 1 week significantly (P < 0.01) decreased the amounts of cholesterol absorbed per day (-85% and -63%, respectively). In contrast, feeding 2% cholesterol for 1 week increased the amounts of absorbed cholesterol 27-fold, even though the percent absorption significantly decreased. With all three treatments, there was a coordinate regulation of total HMG-CoA reductase activity and receptor-mediated LDL binding. Cholesterol feeding downregulated both total jejunal HMG-CoA reductase activity (P < 0.05) and receptor-mediated LDL binding (P < 0.01), whereas lovastatin- and sitosterol-supplemented diets significantly upregulated both of these parameters. In the control, cholesterol-fed, and sitosterol-fed animals, about half of the total jejunal HMG-CoA reductase activity was expressed (in functional dephosphorylated form). However, in the lovastatin-treated rats with 4-fold stimulation of HMG-CoA reductase, only 23% of the total enzyme activity was expressed. Changes in total HMG-CoA reductase activity and receptor-mediated LDL binding in all tested groups occurred with no change in total concentrations of mucosal cholesterol, and only cholesterol-fed animals had increased mucosal esterified cholesterol concentrations. Thus, in response to various fluxes of dietary or newly formed cholesterol, HMG-CoA reductase and receptor-mediated LDL binding are coordinately regulated to maintain constant cellular cholesterol concentrations in the jejunum.