A perivascular origin for mesenchymal stem cells in multiple human organs

Mesenchymal stem cells (MSCs), the archetypal multipotent progenitor cells derived in cultures of developed organs, are of unknown identity and native distribution. We have prospectively identified perivascular cells, principally pericytes, in multiple human organs including skeletal muscle, pancreas, adipose tissue, and placenta, on CD146, NG2, and PDGF-Rbeta expression and absence of hematopoietic, endothelial, and myogenic cell markers. Perivascular cells purified from skeletal muscle or nonmuscle tissues were myogenic in culture and in vivo. Irrespective of their tissue origin, long-term cultured perivascular cells retained myogenicity; exhibited at the clonal level osteogenic, chondrogenic, and adipogenic potentials; expressed MSC markers; and migrated in a culture model of chemotaxis. Expression of MSC markers was also detected at the surface of native, noncultured perivascular cells. Thus, blood vessel walls harbor a reserve of progenitor cells that may be integral to the origin of the elusive MSCs and other related adult stem cells.     

Development of a RIVPACS-type predictive model for bioassessment of wadeable streams in Wyoming

RIVPACS models produce a community-level measure of biological condition known as O/E, which is derived from a comparison of the observed (O) biota with those expected (E) to occur in the absence of anthropogenic stress. We used benthic macroinvertebrate and environmental data collected at 925 stream monitoring stations, from 1993 to 2001, to develop, validate, and apply a RIVPACS model to assess the biological condition of wadeable streams in Wyoming. From this dataset, 296 samples were identified as reference, 157 of which were used to calibrate the model, 46 to validate it, and 93 to examine temporal variability in reference site O/E-values. We used cluster analyses to group the model development reference sites into biologically similar classes of streams and multiple discriminant function analysis to determine which environmental variables best discriminated among reference groups. A suite of 14 categorical and continuous environmental variables best discriminated among 15 reference groups and explained a large proportion of the natural variability in biota within the reference dataset. Eleven of the predictor variables were derived from GIS. As expected, mean O/E-values for reference sites used in model development and validation were near unity and statistically similar. Temporal variability in O/E-values for reference sites was low. Test site values ranged from 0 to 1.45 (mean = 0.73). The model was accurate in both space and time and precise enough (S.D. of O/E-values for calibration data = 0.17) to detect modest alteration in biota associated with anthropogenic stressors. Our model was comparable in performance to other RIVPACS models developed in the United States and can produce effective assessments of biological condition over a broad, ecologically diverse region. We also provide convincing evidence that RIVPACS models can be developed primarily with GIS-based predictor variables. This framework not only simplifies the extraction of predictor variable information while potentially reducing expenditures of time and money in the collection of predictor variable information, but opens the door for development and/or application of RIVPACS models in regions where there is a paucity of local-scale, abiotic information.     

Placebo Use in the United Kingdom: Results from a National Survey of Primary Care Practitioners

Objectives

Surveys in various countries suggest 17% to 80% of doctors prescribe ‘placebos’ in routine practice, but prevalence of placebo use in UK primary care is unknown.

Methods

We administered a web-based questionnaire to a representative sample of UK general practitioners. Following surveys conducted in other countries we divided placebos into ‘pure’ and ‘impure’. ‘Impure’ placebos are interventions with clear efficacy for certain conditions but are prescribed for ailments where their efficacy is unknown, such as antibiotics for suspected viral infections. ‘Pure’ placebos are interventions such as sugar pills or saline injections without direct pharmacologically active ingredients for the condition being treated. We initiated the survey in April 2012. Two reminders were sent and electronic data collection closed after 4 weeks.

Results

We surveyed 1715 general practitioners and 783 (46%) completed our questionnaire. Our respondents were similar to those of all registered UK doctors suggesting our results are generalizable. 12% (95% CI 10 to 15) of respondents used pure placebos while 97% (95% CI 96 to 98) used impure placebos at least once in their career. 1% of respondents used pure placebos, and 77% (95% CI 74 to 79) used impure placebos at least once per week. Most (66% for pure, 84% for impure) respondents stated placebos were ethical in some circumstances.

Conclusion and implications

Placebo use is common in primary care but questions remain about their benefits, harms, costs, and whether they can be delivered ethically. Further research is required to investigate ethically acceptable and cost-effective placebo interventions.     

Material Spiraling in Stream Corridors: A Telescoping Ecosystem Model

Stream ecosystems consist of several subsystems that are spatially distributed concentrically, analogous to the elements of a simple telescope. Subsystems include the central surface stream, vertically and laterally arrayed saturated sediments (hyporheic and parafluvial zones), and the most distal element, the riparian zone. These zones are hydrologically connected; thus water and its dissolved and suspended load move through all of these subsystems as it flows downstream. In any given subsystem, chemical transformations result in a change in the quantity of materials in transport. Processing length is the length of subsystem required to “process” an amount of substrate equal to advective input. Long processing lengths reflect low rates of material cycling. Processing length provides the length dimension of each cylindrical element of the telescope and is specific to subsystem (for example, the surface stream), substrate (for instance, nitrate), and process (denitrification, for example). Disturbance causes processing length to increase. Processing length decreases during succession following disturbance. The whole stream-corridor ecosystem consists of several nested cylindrical elements that extend and retract, much as would a telescope, in response to disturbance regime. This telescoping ecosystem model (TEM) can improve understanding of material retention in running water systems; that is, their “nutrient filtration” capacity. We hypothesize that disturbance by flooding alters this capacity in proportion to both intensity of disturbance and to the relative effect of disturbance on each subsystem. We would expect more distal subsystems (for example, the riparian zone) to show the highest resistance to floods. In contrast, we predict that postflood recovery of functions such as material processing (that is, resilience) will be highest in central elements and decrease laterally. Resistance and resilience of subsystems are thus both inversely correlated and spatially separated. We further hypothesize that cross-linkages between adjacent subsystems will enhance resilience of the system as a whole. Whole-ecosystem retention, transformation, and transport are thus viewed as a function of subsystem extent, lateral and vertical linkage, and disturbance regime. Received 15 April 1997; accepted 1 September 1997.     

Comparative analysis of microbiota along the length of the gastrointestinal tract of two tree squirrel species (Sciurus aberti and S. niger) living in sympatry

Microbiota inhabiting the gastrointestinal (GI) tract of animals has important impacts on many host physiological processes. Although host diet is a major factor influencing the composition of the gut micro‐organismal community, few comparative studies have considered how differences in diet influence community composition across the length of the GI tract. We used 16S sequencing to compare the microbiota along the length of the GI tract in Abert's (Sciurus aberti) and fox squirrels (S. niger) living in the same habitat. While fox squirrels are generalist omnivores, the diet of Abert's squirrels is unusually high in plant fiber, particularly in winter when they extensively consume fiber‐rich inner bark of ponderosa pine (Pinus ponderosa). Consistent with previous studies, microbiota of the upper GI tract of both species consisted primarily of facultative anaerobes and was less diverse than that of the lower GI tract, which included mainly obligate anaerobes. While we found relatively little differentiation between the species in the microbiota of the upper GI tract, the community composition of the lower GI tract was clearly delineated. Notably, the Abert's squirrel lower GI community was more stable in composition and enriched for microbes that play a role in the degradation of plant fiber. In contrast, overall microbial diversity was higher in fox squirrels. We hypothesize that these disparities reflect differences in diet quality and diet breadth between the species.     

Receptor-Mediated Stimulation and Inhibition of Nerve Growth Factor Secretion by Vascular Smooth Muscle

Nerve growth factor (NGF) is a potent neurotrophin signaling protein, the best-known member of a family of similar neurotrophins. Specific neuronal populations depend upon the neurotrophins for normal function and disturbances in NGF and neurotrophin supply have been implicated in neurodegenerative disease, diabetes, and hypertension. This report details experiments in which the hourly pattern of NGF secretion by cultured vascular smooth muscle cells is examined. Vascular smooth muscle cells are major innervation targets of the neuronal population first discovered to be NGF-dependent: the sympathetic principal neurons. The results show that arginine vasopressin (AVP), angiotensin II (AngII), and α-adrenergic receptor activation, all contractile stimuli, elevate NGF secretion. However, AVP dependably does so alone while AngII requires coactivation of adenosine receptors. Adenosine alone inhibits secretion and the α-adrenergic increase in NGF output can be antagonized by activation of β-adrenergic receptors. A change to fresh culture medium is also a potent stimulus to increased NGF output.     

The Role of Climatic Factors in the Expression of an Intrasexual Signal in the Paper Wasp Polistes dominulus

Within a species, variation in the use of sexual signals is observed between different populations. For intersexual traits, differences in the environmental conditions experienced by populations can play an important role in driving variation in male ornaments and female preferences. However, little is known about the factors maintaining variation in intrasexual traits used in competition. In this study, we investigate the role of climatic conditions in maintaining variation in the expression of an intrasexual signal in the paper wasp Polistes dominulus. The results of an experiment in which pupae were housed under different temperature and humidity conditions revealed a strong effect of temperature during pupal development on the expression of the signal. Furthermore, a comparison of survival and body weight between wasps reared at different temperatures indicates that signal expression exhibits phenotypic plasticity in response to developmental temperature. The effect of temperature on signal expression is consistent with patterns of signal expression observed across populations in the wild and suggests that climatic conditions may act to constrain signal expression in some populations but not in others, driving variation in signal use within P. dominulus. Environmental conditions may therefore be important in defining the scope for intrasexual signalling in animal populations and, in doing so, may play a role in maintaining variation in intrasexual traits in the face of sexual selection.     

Molecular Imaging Reveals a Progressive Pulmonary Inflammation in Lower Airways in Ferrets Infected with 2009 H1N1 Pandemic Influenza Virus

Molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics. Herein we used [¹⁸F]-2-deoxy-2-fluoro-D-glucose ([¹⁸F]-FDG) as a radiotracer for PET imaging coupled with CT (FDG-PET/CT) to gain insight into the spatiotemporal progression of the inflammatory response of ferrets infected with a clinical isolate of a pandemic influenza virus, H1N1 (H1N1pdm). The thoracic regions of mock- and H1N1pdm-infected ferrets were imaged prior to infection and at 1, 2, 3 and 6 days post-infection (DPI). On 1 DPI, FDG-PET/CT imaging revealed areas of consolidation in the right caudal lobe which corresponded with elevated [¹⁸F]-FDG uptake (maximum standardized uptake values (SUVMax), 4.7–7.0). By days 2 and 3, consolidation (CT) and inflammation ([¹⁸F]-FDG) appeared in the left caudal lobe. By 6 DPI, CT images showed extensive areas of patchy ground-glass opacities (GGO) and consolidations with the largest lesions having high SUVMax (6.0–7.6). Viral shedding and replication were detected in most nasal, throat and rectal swabs and nasal turbinates and lungs on 1, 2 and 3 DPI, but not on day 7, respectively. In conclusion, molecular imaging of infected ferrets revealed a progressive consolidation on CT with corresponding [¹⁸F]-FDG uptake. Strong positive correlations were measured between SUVMax and bronchiolitis-related pathologic scoring (Spearman’s ρ = 0.75). Importantly, the extensive areas of patchy GGO and consolidation seen on CT in the ferret model at 6 DPI are similar to that reported for human H1N1pdm infections. In summary, these first molecular imaging studies of lower respiratory infection with H1N1pdm show that FDG-PET can give insight into the spatiotemporal progression of the inflammation in real-time.