Vasoconstriction in active skeletal muscles: a potential role for P2X purinergic receptors?

There is evidence that ATP acts as a neurotransmitter in vascular smooth muscle and is coreleased with norepinephrine from sympathetic nerves. We hypothesized that P2X-receptor stimulation with the selective P2X-receptor agonist alpha,beta-methylene ATP would produce vasoconstriction in resting and exercising skeletal muscle. Six mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. The selective P2X agonist alpha,beta-methylene ATP was infused as a bolus into the femoral artery catheter at rest and during mild, moderate, and heavy exercise. Intra-arterial infusions of alpha,beta-methylene ATP elicited reductions in vascular conductance of 54 +/- 5, 49 +/- 8, 39 +/- 8, and 30 +/- 6% at rest, 3 miles/h, 6 miles/h, and 6 miles/h at a 10% grade, respectively. The agonist infusions did not affect blood flow in the contralateral iliac artery. To examine whether nitric oxide is responsible for the attenuated vasoconstrictor response to P2X stimulation, the infusions were repeated in the presence of NG-nitro-l-arginine methyl ester. After nitric oxide synthase blockade, intra-arterial infusions of alpha,beta-methylene ATP elicited reductions in vascular conductance of 56 +/- 7, 61 +/- 8, 52 +/- 9, and 40 +/- 7% at rest, 3 miles/h, 6 miles/h, and 6 miles/h at a 10% grade, respectively. P2X-receptor responsiveness was attenuated during exercise compared with rest. Blockade of nitric oxide production did not affect the attenuation of P2X-receptor responsiveness during exercise. These data support the hypothesis that P2X purinergic receptors can produce vasoconstriction in exercising skeletal muscle.     

Imagining the Future of the Anthropology of Education if We Take Laura Nader Seriously

The large corpus of scholarship of cultural anthropologist Laura Nader is relevant to the contemporary practice of the anthropology of education. In particular, her work is relevant to contemporary debates about methodology and what constitutes "scientifically based" education research; to the prospect and need for more crossfertilization within the discipline of anthropology; and for the proud assertion of anthropology's distinctive suitability for understanding and responding to many contemporary educational challenges, including how to have anthropologically derived insights more favorably compete in the "marketplace of ideas" against less empirically grounded claims and strategies.     

Non-linearities, synergisms and plant extinctions in South African fynbos and Australian kwongan

This paper explores the determinants of extinction of endemic plant taxa in mediterranean-climate regions in South Africa and southwestern Australia. Major threats to biodiversity in these areas include agriculture, deforestation, fragmentation, invasive alien organisms and urbanization. Case studies from the two regions show that synergisms between factors can lead to discontinuous, or non-linear, responses that have increased extinction rates (or threaten to) beyond predictions based on simple deterministic processes.     

Relationship Between Substrate Concentration and Fermentation Product Ratios in Clostridium thermocellum Cultures

Growth of Clostridium thermocellum in batch cultures was studied over a broad range of cellobiose concentrations. Cultures displayed important differences in their substrate metabolism as determined by the end product yields. Bacterial growth was severely limited when the initial cellobiose concentration was 0.2 (wt/vol), was maximal at substrate concentrations between 0.5 and 2.0%, and did not occur at 5.0% cellobiose. Ethanol accumulated maximally (38.3 μmol/10⁹ cells) in cultures with an initial cellobiose concentration of 0.8%, whereas cultures in 2.0% cellobiose accumulated only 17.3 μmol, and substrate-limited cultures (0.2% cellobiose) accumulated little, if any, ethanol beyond that initially detected (8.3 μmol/10⁹ cells). In a medium with 0.8% cellobiose, ethanol was produced at a constant rate of approximately 1.1 μmol/10⁹ cells per h from late-logarithmic phase (16 h) of growth well into stationary phase (44 h). When ethanol was added exogenously at levels more than twice the maximum produced by the cultures themselves (0.5% [vol/vol]), neither the extent of growth (maximum Klett units, 150) nor the amounts of ethanol produced (~0.17%) by the culture was affected. The ratio of ethanol to acetate was highest (2.8) when cells were grown in 0.8% cellobiose and lowest (1.2) when cells were grown in 0.2% cellobiose.     

Isolation and characterization of the thymus-brain antigen (analogous to thy-1 antigen) from human brain.

1. The human thymus-brain antigen, which corresponds to the murine (mouse or rat) Thy-1 antigen complex, was isolated from brain after solubilization in deoxycholate by gel-permeation chromatography, wheat-germ-lectin affinity chromatography and ion-exchange chromatography. 2. The isolated antigen is a glycoprotein displaying an apparent molecular weight of 26 000-29 000 in sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. 3. No antigen activity was found with the lipid fraction from human brain. 4. The protein has a tendency for spontaneous self-association (dimerization), leading to aggregates resistant to dissociating and reducing agents on prolonged storage. 5. The antigen is microheterogeneous with respect to size, charge (approximate isoelectric points of the monomer 7.7, 7.0 and 6.5) and to lectin-binding affinity. 6. The antigen can be reconstituted to protein-lipid vesicles. The antigen activity of solubilized antigen is strongly increased by reconstitution and that of membranes decreased by solubilization with detergent.     

The heart of what's the matter The semantics of illness in Iran

Our understanding of the psychosocial and cultural dimensions of disease and illness is limited not merely by a lack of empirical knowledge but also by an inadequate medical semantics. The empiricist theories of medical language commonly employed both by comparative ethnosemantic studies and by medical theory are unable to account for the integration of illness and the language of high medical traditions into distinctive social and symbolic contexts. A semantic network analysis conceives the meaning of illness categories to be constituted not primarily as an ostensive relationship between signs and natural disease entities but as a syndrome of symbols and experiences which typically run together for the members of a society. Such analysis dirests our attention to the patterns of associations which provide meaning to elements of a medical lexicon and to the constitution of that meaning through the use of medical discourse to articulate distinctive configurations of social stress and to negotiate relief for the sufferer. This paper provides a critical discussion of medical semantics and develops a semantic network analysis of heart distress, a folk illness in Iran.     

Empirical choice of sampling procedures for optimal research design in the longitudinal study of primate behavior

A method is suggested to evaluate on an empirical basis sampling plans for the longitudinal study of primate behavior in those very common situations in which the mathematical structure of behavior is unknown. The method is based on a randomization procedure applied to a pilot sample of the behavior organized so that cost of implementation of a sampling plan can be evaluated vis á vis the sampling error intrinsic to the plan.     

Inferences about the conformation of somatostatin at a biologic receptor based on NMR studies

Examination of two diastereomeric analogs of somatostatin differing in stereochemistry at the tryptophan residue has revealed a high field resonance in the -Trp isomer which is assigned to the γ-methylene of Lys⁹. The extent of correlation of this shift with biologic activity for a series of analogs of somatostatin is discussed. From comparison of close analogs, it is suggested that the biologically active conformation of somatostatin at the receptor controlling insulin release is not the major conformation of this hormone in solution. It is suggested that the conformation of somatostatin at this receptor resembles more closely the solution conformation of analogs having tryptophan in the -configuration. This latter conformation places the Trp⁸-Lys⁹ side chains in close proximity, thus shifting the γ-methylene protons of Lys⁹ upfield.     

Activation of MAP kinases by calcium-dependent and calcium-independent pathways. Stimulation by thapsigargin and epidermal growth factor.

In order to determine the effect of calcium mobilization on mitogen-activated protein (MAP) kinase activation, we have treated human foreskin fibroblasts (HSWP cells) and human epidermal carcinoma (A431) cells with thapsigargin. Intracellular free calcium was monitored by single cell image analysis using fura-2 and correlated with MAP kinase stimulation as assessed by immunoprecipitation, kinase renaturation assays and immunoblotting. Thapsigargin stimulated the 44- and 42-kDa MAP kinase isozymes in both cell types with kinetics that were slightly delayed relative to enzyme stimulated by epidermal growth factor. Removal of external calcium did not significantly affect the activation of the MAP kinases by thapsigargin, indicating that intracellular calcium mobilization is sufficient to stimulate the enzymes. However, treatment of cells with EGTA under conditions which deplete both intra- and extracellular calcium inhibited stimulation by thapsigargin but not epidermal growth factor. Stimulation of the MAP kinases by the calcium ionophore ionomycin paralleled the activation observed with thapsigargin in both calcium-containing and calcium-free conditions. These results indicate that there are at least two independent pathways for stimulation of MAP kinase: one that is dependent on intracellular calcium mobilization, and one that is mediated by the tyrosine kinase epidermal growth factor receptor and is calcium-independent.