The interactive effects of parasites, disturbance, and productivity on experimental adaptive radiations

Disturbance, productivity, and natural enemies are significant determinants of the evolution of diversity, but their interactive effect remains unresolved. We develop a simple, qualitative model assuming trade-offs between growth rate, competitive ability and parasite resistance, to address the interactive effects of these variables on the evolution of host diversity. Consistent with previous studies our model predicts maximum diversity at intermediate levels of disturbance and productivity in the absence of parasitism. However, parasites break down these unimodal diversity relationships with productivity and disturbance, as selection for parasite resistance reduces the importance of growth rate-competitive ability trade-offs. We tested these predictions using the bacterium Pseudomonas fluorescens, which undergoes an adaptive radiation into spatial niche specialists under laboratory conditions. This is the first study of adaptive radiation in response to experimental manipulation of the three-way interaction between productivity, disturbance, and natural enemies. As hypothesized, unimodal diversity relationships with disturbance and productivity were weakened or disappeared in the presence of parasitic phages. This was the result of phages increasing diversity at environmental extremes, by imposing selection for phage-resistant variants, but decreasing diversity in less stressful environments, probably through reductions in resource competition. Phages had a net effect of increasing host diversity. Parasites and other natural enemies are therefore likely to have a large effect in mitigating the influence of other environmental variables on the evolution and maintenance of diversity.     

Clinical and behavioural risk indicators for root caries in older people

Objective: To investigate the clinical and behavioural factors indicating root caries risk among older people. Desing: Cross sectional clinical and interview data from the National Diet and Nutrition Survey (aged 65 years and over) in Great Britain. Logistic regression models of the prevalence of root caries and linear regression models of the extent of root caries were constructed to quantify the role of a range of clinical and behavioural risk indicators, including sugars intake. Setting: A national sample of older British adults, free‐living and institutionalised. Participants: 462 dentate adults aged 65 years or over. Results: Nine or more intakes of sugars per day more than doubled the odds of root caries being present (OR 2.2–2.4). Other clinical and behavioural factors affecting root caries included wearing a partial denture in the presence of heavy plaque deposits (OR 2.1–2.6) and infrequent tooth brushing (OR 2.8 – 4.1). Linear regression models showed that, amongst those that had root caries, sucking sweets in the presence of a dry mouth, poor hygiene, partial dentures and living in an institution contributed to the extent of root caries, as measured by the RCI(d). Conclusions: Of the factors open to possible clinical or behavioural intervention, frequent sugars intake, poor hygiene and partial dentures were all associated with large increases in risk.     

Using plasma membrane nanoclusters to build better signaling circuits

Cellular signaling pathways do not simply transmit data; they integrate and process signals to operate as switches, oscillators, logic gates, memory modules and many other types of control system. These complex processing capabilities enable cells to respond appropriately to the myriad of external cues that direct growth and development. The idea that crosstalk and feedback loops are used as control systems in biological signaling networks is well established. Signaling networks are also subject to exquisite spatial regulation, yet how spatial control modulates signal outputs is less well understood. Here, we explore the spatial organization of two different signal transduction circuits: receptor tyrosine kinase activation of the mitogen-activated protein kinase module; and glycosylphosphatidylinositol-anchored receptor activation of phospholipase C. With regards to these pathways, recent results have refocused attention on the crucial role of lipid rafts and plasma membrane nanodomains in signal transmission. We identify common design principals that highlight how the spatial organization of signal transduction circuits can be used as a fundamental control mechanism to modulate system outputs in vivo.     

Validation of an EMG-driven, graphically based isometric musculoskeletal model of the cervical spine

EMG-driven musculoskeletal modeling is a method in which loading on the active and passive structures of the cervical spine may be investigated. A model of the cervical spine exists; however, it has yet to be criterion validated. Furthermore, neck muscle morphometry in this model was derived from elderly cadavers, threatening model validity. Therefore, the overall aim of this study was to modify and criterion validate this preexisting graphically based musculoskeletal model of the cervical spine. Five male subjects with no neck pain participated in this study. The study consisted of three parts. First, subject-specific neck muscle morphometry data were derived by using magnetic resonance imaging. Second, EMG drive for the model was generated from both surface (Drive 1: N=5) and surface and deep muscles (Drive 2: N=3). Finally, to criterion validate the modified model, net moments predicted by the model were compared against net moments measured by an isokinetic dynamometer in both maximal and submaximal isometric contractions with the head in the neutral posture, 20 deg of flexion, and 35 deg of extension. Neck muscle physiological cross sectional area values were greater in this study when compared to previously reported data. Predictions of neck torque by the model were better in flexion (18.2% coefficient of variation (CV)) when compared to extension (28.5% CV) and using indwelling EMG did not enhance model predictions. There were, however, large variations in predictions when all the contractions were compared. It is our belief that further work needs to be done to improve the validity of the modified EMG-driven neck model examined in this study. A number of factors could potentially improve the model with the most promising probably being optimizing various modeling parameters by using methods established by previous researchers investigating other joints of the body.     

Characterization of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) as an inhibitor of brain glycogen shunt activity

The pharmacological properties of 1,4-dideoxy-1,4-imino- d -arabinitol (DAB), a potent inhibitor of glycogen phosphorylase and synthase activity in liver preparations, were characterized in different brain tissue preparations as a prerequisite for using it as a tool to investigate brain glycogen metabolism. Its inhibitory effect on glycogen phosphorylase was studied in homogenates of brain tissue and astrocytes and IC₅₀-values close to 400 nM were found. However, the concentration of DAB needed for inhibition of glycogen shunt activity, i.e. glucose metabolism via glycogen, in intact astrocytes was almost three orders of magnitude higher. Additionally, such complete inhibition required a pre-incubation period, a finding possibly reflecting a limited permeability of the astrocytic membrane. DAB did not affect the accumulation of 2-deoxyglucose-6-phosphate indicating that the transport of DAB is not mediated by the glucose transporter. DAB had no effect on enzymes involving glucose-6-phosphate, i.e. glucose-6-phosphate dehydrogenase, phosphoglucoisomerase and hexokinase. Furthermore, DAB was evaluated in a functional preparation of the isolated mouse optic nerve, in which its presence severely reduced the ability to sustain evoked compound action potentials in the absence of glucose, a condition in which glycogen serves as an important energy substrate. Based on the experimental findings, DAB can be used to evaluate glycogen shunt activity and its functional importance in intact brain tissue and cells at a concentration of 300–1000 μM and a pre-incubation period of 1 h.     

Expression of Fc alpha/mu receptor by human mesangial cells: a candidate receptor for immune complex deposition in IgA nephropathy.

IgA nephropathy is characterized by the deposition of IgA immune complexes in the glomerular mesangium, but the mechanisms responsible for this are not well understood. Human mesangial cells (HMCs) can bind IgA but do not express known IgA receptors. We show here that primary HMCs express mRNA for a novel receptor, the Fc alpha/mu receptor (Fcalpha/muR), and that receptor expression is upregulated by IL-1. We also detected mRNA for a novel receptor variant in HMCs that may encode a soluble form of the receptor. Fcalpha/muR was expressed in a heterologous system which showed that the receptor was approximately 58 kDa in weight and was only minimally N-glycosylated. As predicted from the characteristics of the murine homologue, the expressed human Fcalpha/muR was able to bind IgA and IgM, but not IgG. These results suggest that Fcalpha/muR may be the receptor responsible for mesangial IgA deposition in IgA nephropathy.     

Escherichia coli O157:H7 colonization in small domestic ruminants

Enterohaemorrhagic Escherichia coli O157:H7 was first implicated in human disease in the early 1980s, with ruminants cited as the primary reservoirs. Preliminary studies indicated cattle to be the sole source of E. coli O157:H7 outbreaks in humans; however, further epidemiological studies soon demonstrated that E. coli O157:H7 was widespread in other food sources and that a number of transmission routes existed. More recently, small domestic ruminants (sheep and goats) have emerged as important sources of E. coli O157:H7 human infection, particularly with the widespread popularity of petting farms and the increased use of sheep and goat food products, including unpasteurized cheeses. Although the colonization and persistence characteristics of E. coli O157:H7 in the bovine host have been studied intensively, this is not the case for small ruminants. Despite many similarities to the bovine host, the pathobiology of E. coli O157:H7 in small domestic ruminants does appear to differ significantly from that described in cattle. This review aims to critically review the current knowledge regarding colonization and persistence of E. coli O157:H7 in small domestic ruminants, including comparisons with the bovine host where appropriate.