Interaction of guanine nucleotides with adenylate cyclase in normal and spontaneously transformed RL-RP-C cloned rat hepatocytes

Spontaneous transformation of RL-PR-C hepatocytes leads to alterations in the adenylate cyclase complex which include a lower than normal basal level of activity, a loss of sensitivity to exogenous GTP, and a decreased sensitivity to isoproterenol. Both normal and transformed membranes possess substantial GTPase activity. Treatment of transformed hepatocyte membranes with either isoproterenol plus GMP or with cholera toxin, under conditions that displace tightly bound GDP, restored the GTP effect on adenylate cyclase, and eliminated the lag in the activation by guanyl-5'-yl-imidodiphosphate. Such pretreatment also enhanced guanine nucleotide effects on the adenylate cyclase of normal hepatocytes. These results are explainable on the basis that transformation increases adenylate cyclase-associated GTPase activity, and increases occupancy of nucleotide regulatory sites by inactive or inhibitory guanine nucleotides, e.g., GDP. Seemingly, both catecholamines and cholera toxin promote an exchange reaction at the regulatory sites, resulting in clearance of these sites of inhibitory nucleotides.     

Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site

Background  

Ricin is a potent toxin and known bioterrorism threat with no available antidote. The ricin A-chain (RTA) acts enzymatically to cleave a specific adenine base from ribosomal RNA, thereby blocking translation. To understand better the relationship between ligand binding and RTA active site conformational change, we used a fragment-based approach to find a minimal set of bonding interactions able to induce rearrangements in critical side-chain positions.     

Anaerobic Granular Sludge Bioreactor Technology

Anaerobic digestion is a mature wastewater treatment technology, with worldwide application. The predominantly applied bioreactor designs, such as the upflow anaerobic sludge blanket and expanded granular sludge bed, are based on the spontaneous formation of granular sludge. Despite the exploitation of granular reactors at full-scale for more than two decades, the mechanisms of granulation are not completely understood and numerous theories have been put forward to describe the process from a biological, ecological and engineering point of view. New technological opportunities are emerging for anaerobic digestion, aided by an improved understanding of microbiological and environmental factors affecting the formation and activity of anaerobic granular sludge.     

Mathematical Models of Cell Motility

Cell motility is an essential biological action in the creation, operation and maintenance of our bodies. Developing mathematical models elucidating cell motility will greatly advance our understanding of this fundamental biological process. With accurate models it is possible to explore many permutations of the same event and concisely investigate their outcome. While great advancements have been made in experimental studies of cell motility, it now has somewhat fallen on mathematical models to taking a leading role in future developments. The obvious reason for this is the complexity of cell motility. Employing the processing power of today’s computers will give researches the ability to run complex biophysical and biochemical scenarios, without the inherent difficulty and time associated with in vitro investigations. Before any great advancement can be made, the basics of cell motility will have to be well-defined. Without this, complicated mathematical models will be hindered by their inherent conjecture. This review will look at current mathematical investigations of cell motility, explore the reasoning behind such work and conclude with how best to advance this interesting and challenging research area.     

Occupancy and co-occurrence patterns of endemic mammals and introduced predators across a broad geographical gradient in eastern Australia

Biodiversity and Conservation - Invasive predators, land clearing and altered fire regimes have been implicated in species decline and extinction worldwide. Enhanced knowledge of how these factors...     

Long-chain Acylcarnitines Reduce Lung Function by Inhibiting Pulmonary Surfactant

The role of mitochondrial energy metabolism in maintaining lung function is not understood. We previously observed reduced lung function in mice lacking the fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase (LCAD). Here, we demonstrate that long-chain acylcarnitines, a class of lipids secreted by mitochondria when metabolism is inhibited, accumulate at the air-fluid interface in LCAD^−/− lungs. Acylcarnitine accumulation is exacerbated by stress such as influenza infection or by dietary supplementation with l-carnitine. Long-chain acylcarnitines co-localize with pulmonary surfactant, a unique film of phospholipids and proteins that reduces surface tension and prevents alveolar collapse during breathing. In vitro, the long-chain species palmitoylcarnitine directly inhibits the surface adsorption of pulmonary surfactant as well as its ability to reduce surface tension. Treatment of LCAD^−/− mice with mildronate, a drug that inhibits carnitine synthesis, eliminates acylcarnitines and improves lung function. Finally, acylcarnitines are detectable in normal human lavage fluid. Thus, long-chain acylcarnitines may represent a risk factor for lung injury in humans with dysfunctional fatty acid oxidation.     

Anaerobic treatment of 2,4,6-trichlorophenol in an expanded granular sludge bed-anaerobic filter (EGSB-AF) bioreactor at 15 degrees C

Expanded granular sludge bed-anaerobic filter (EGSB-AF) bioreactors were operated at 15 degrees C for the treatment of 2,4,6-trichlorophenol (TCP)-containing volatile fatty acid (VFA)-based wastewaters. The seed sludge used as inoculum for the control (no TCP) and test reactor was unexposed to chlorophenols (CPs) prior to the 425-day trial. TCP supplementation to the feed at 50 mg TCPl(-1) partially inhibited the anaerobic degradation of the VFA feed measured as COD removal efficiency. However, the withdrawal and subsequent application of stepwise increments to the TCP loading resulted in steady COD removal. Terminal restriction fragment length polymorphism analysis showed Methanosaeta-like Archaea in the control reactor over the experimental period. Different methanogenic populations were detected in the test reactor and responded to the changes in feed composition. Bacterial community analyses indicated changes in the community structure over time and suggested the presence of Campylobacter-like, Acidimicrobium-like and Heliophilum-like organisms in the samples. TCP mineralisation was by a reductive dechlorination pathway through 2,4-dichlorophenol (DCP) and 4-chlorophenol (4-CP) or 2-chlorophenol (2-CP). CP degradation rates in sludge granules from the lower chamber of the hybrid EGSB-AF reactor was in the order TCP > DCP > 4-CP > 2-CP. However, a biodegradability order of lower CPs > TCP was observed in fixed-film biomass taken from the upper reactor chamber, thus reflecting the role of this reactor section in the metabolism of residual lower CPs from the lower sludge-bed stage of operation.     

A prediction of cell differentiation and proliferation within a collagen–glycosaminoglycan scaffold subjected to mechanical strain and perfusive fluid flow

Mesenchymal stem cell (MSC) differentiation can be influenced by biophysical stimuli imparted by the host scaffold. Yet, causal relationships linking scaffold strain magnitudes and inlet fluid velocities to specific cell responses are thus far underdeveloped. This investigation attempted to simulate cell responses in a collagen–glycosaminoglycan (CG) scaffold within a bioreactor. CG scaffold deformation was simulated using μ-computed tomography (CT) and an in-house finite element solver (FEEBE/linear). Similarly, the internal fluid velocities were simulated using the afore-mentioned μCT dataset with a computational fluid dynamics solver (ANSYS/CFX). From the ensuing cell-level mechanics, albeit octahedral shear strain or fluid velocity, the proliferation and differentiation of the representative cells were predicted from deterministic functions. Cell proliferation patterns concurred with previous experiments. MSC differentiation was dependent on the level of CG scaffold strain and the inlet fluid velocity. Furthermore, MSC differentiation patterns indicated that specific combinations of scaffold strains and inlet fluid flows cause phenotype assemblies dominated by single cell types. Further to typical laboratory procedures, this predictive methodology demonstrated loading-specific differentiation lineages and proliferation patterns. It is hoped these results will enhance in-vitro tissue engineering procedures by providing a platform from which the scaffold loading applications can be tailored to suit the desired tissue.     

海南俄贤岭石灰岩山地海南大戟灌丛群落研究

根据样方调查,对海南俄贤岭自然保护区海南大戟灌丛群落的种类组成、外貌、结构特征和物种多样性进行分析。结果表明,在700m2样地中,有维管植物77种,隶属于47科70属。群落中乔木的个体数量很少,主要由灌木和草本组成,灌木层主要优势种为海南大戟等。群落外貌常绿,生活型以小高位芽为主,占22.08%;按照Raunkiaer的频度等级定律,属于B级的种类最多,频度值为43.42。整个群落的物种丰富度Magarlef指数为8.56,Shannon-Wiener指数为1.38,Simposon为0.90,均匀度指数为0.32。群落各层次的丰富度格局表现为灌木层>草本层>乔木层>藤本植物,多样性格局为灌木层>乔木层>草本层<(>)藤本植物,均匀度格局为乔木层>藤本植物>灌木层>草本层。