Effects of carbohydrate availability on lipogenesis in sheep

1. Lipogenesis in sheep liver and adipose tissue was investigated by incorporation studies in vitro with radioactive glucose and acetate and by assays of key enzymes. 2. Carbohydrate availability to sheep was increased by feeding on a diet containing 70% soluble carbohydrate, by infusing glucose into the abomasum or by direct intravenous infusion of glucose. 3. Under these conditions lipogenesis from glucose and acetate was increased from very low values in lìver and adipose tissue, especially in those animals where rumen fermentation was by-passed by glucose infusion. 4. Large increases in the activities of ATP citrate lyase (EC 4.1.3.8) and NADP-malate dehydrogenase (EC 1.1.1.40) occurred in both tissues when lipogenesis was increased. 5. No adaptations were found in the activities of pyruvate carboxylase (EC 6.4.1.1) in adipose tissue, glucokinase (EC 2.7.1.2) in liver or 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) in liver. It is proposed that the absence of these enzymes is not related to glucose availability. 6. The effect of glucose on liver lipogenesis was to increase conversion of acetate into lipid. 7. This effect also occurred in adipose tissue, but in this tissue glucose also became a quantitatively important precursor of triglyceride fatty acid.     

Non‐adaptive phenotypic plasticity: the effects of terrestrial and aquatic herbicides on larval salamander morphology and swim speed

Phenotypic plasticity, although ubiquitous, may not always be advantageous. Non‐adaptive plasticity is likely to occur in response to novel environmental stress. Anthropogenic contaminants, such as herbicides, are novel stressors that are not present in the evolutionary history of most species. We investigated the pattern and consequences of phenotypic plasticity induced by four glyphosate‐based herbicides (two terrestrial and two aquatic) in larvae of the spotted salamander, Ambystoma maculatum, by determining (1) whether the herbicides induced different morphologies; (2) if different morphologies translated to differences in burst swim performance; and (3) how induced individuals performed relative to non‐induced controls. Different herbicide formulations led to the production of significantly different head and tail morphologies, and tail morphology correlated with fastest escape speed. However, escape speed did not vary among treatments. In addition, three out of four herbicide treatments experienced accelerated growth rates, in terms of the lateral size of tails, although the tail shapes were either similar to preliminary controls or intermediate between preliminary and final controls. These observations suggest that herbicide‐induced morphology is a case of non‐adaptive phenotypic plasticity, and that there is potentially a trade‐off between growth and development for larvae exposed to different formulations. Understanding the functional significance of induced phenotypes is important for determining their importance in shaping an organism's ecological interactions and evolutionary trajectories. Furthermore, under different conditions, the morphological changes that we observed in response to exposure to herbicides might affect salamander fitness and influence population dynamics.     

The relationship between nernst equilibrium variability and the multifractality of interspike intervals in the hippocampus

Spatiotemporal patterns of action potentials are considered to be closely related to information processing in the brain. Auto-generating neurons contributing to these processing tasks are known to cause multifractal behavior in the inter-spike intervals of the output action potentials. In this paper we define a novel relationship between this multifractality and the adaptive Nernst equilibrium in hippocampal neurons. Using this relationship we are able to differentiate between various drugs at varying dosages. Conventional methods limit their ability to account for cellular charge depletion by not including these adaptive Nernst equilibria. Our results provide a new theoretical approach for measuring the effects which drugs have on single-cell dynamics.     

Short-Term Antiretroviral Treatment Recommendations Based on Sensitivity Analysis of a Mathematical Model for HIV Infection of CD4<Superscript>+</Superscript>T Cells

HIV infection is one of the most difficult infections to control and manage. The most recent recommendations to control this infection vary according to the guidelines used (US, European, WHO) and are not patient-specific. Unfortunately, no two individuals respond to infection and treatment quite the same way. The purpose of this paper is to make use of the uncertainty and sensitivity analysis to investigate possible short-term treatment options that are patient-specific. We are able to identify the most significant parameters that are responsible for ART outcome and to formulate some insights into the ART success.     

Thermoreversible hydrogels from RAFT-synthesized BAB triblock copolymers: steps toward biomimetic matrices for tissue regeneration

Narrowly dispersed, temperature-responsive BAB block copolymers capable of forming physical gels under physiological conditions were synthesized via aqueous reversible addition fragmentation chain transfer (RAFT) polymerization. The use of a difunctional trithiocarbonate facilitates the two-step synthesis of BAB copolymers with symmetrical outer blocks. The outer B blocks of the triblock copolymers consist of poly(N-isopropylacrylamide) (PNIPAM) and the inner A block consists of poly(N,N-dimethylacrylamide). The copolymers form reversible physical gels above the phase transition temperature of PNIPAM at concentrations as low as 7.5 wt % copolymer. Mechanical properties similar to collagen, a naturally occurring polypeptide used as a three-dimensional in vitro cell growth scaffold, have been achieved. Herein, we report the mechanical properties of the gels as a function of solvent, polymer concentration, and inner block length. Structural information about the gels was obtained through pulsed field gradient NMR experiments and confocal microscopy.     

Expression and function of T cell homing molecules in Hodgkin’s lymphoma

Circulating T lymphocytes enter a tissue if they express appropriate chemokine receptors and adhesion molecules to engage ligands presented at this site. To aid rational development of T cell-based therapies for Hodgkin's lymphoma (HL), we have assessed the expression and function of homing receptors on tumour-infiltrating T cells in HL and compared them with T cells from unaffected lymph nodes and colorectal cancer tissue. Chemokine receptors CXCR3, CXCR4 and CCR7 were expressed on a large proportion of T cells within HL tissue and mediated chemotaxis to purified chemokine. The corresponding ligands (CXCL10, CXCL12, CCL21) were expressed on the malignant cells and/or vascular endothelium. Adhesion molecules including CD62L were widely expressed on HL-derived T cells and their corresponding ligands were detected on vessels within the tumour. This homing phenotype was distinct from T cells isolated from colorectal cancer, but matched closely the phenotype of T cells from unaffected lymph nodes. Thus, T cell recruitment to HL resembles entry of na?ve/central memory T cells into normal lymph nodes. This has important implications for current approaches to treat HL using T cells activated and expanded in vitro that lack CCR7 and CD62L expression.