Noninvolvement of a rat intestinal folate binding protein in physiological folate absorption

Summary Folic acid and its derivatives are observed to be instantaneously bound to rat intestinal mucosal cell curface binding protein. Various parameters were measured such as the optimal pH for binding (6.5), the saturation kinetics observed for folate binding and the avid affinity with which polyglutamyl folates are preferentially bound to the binder. A comparison of the observed results with the conditions reported as favorable for intestinal folate absorption in the rat precludes the involvement of this folate-binding protein in the physiological absorption of folates.     

The x-phi(les): unusual insights into the nature of inquiry

Experimental philosophy is often regarded as a category mistake. Even those who reject that view typically see it as irrelevant to standard philosophical projects. We argue that neither of these claims can be sustained and illustrate our view with a sketch of the rich interconnections with philosophy of science.     

Androgen receptor in the thumb pads ofRana esculenta

Riassunto E' stato messo in evidenza un recettore per gli androgeni nel sopranatante a 105.000×g della callosità del pollice diRana esculenta. Si é visto che competono fortemente col testosterone-H³ il testosterone, il diidrotestosterone, l'11-chetotestosterone e l'acetato di ciproterone; mentre non competono l'estradiolo-17, il cortisolo ed il ciproterone libero. La costante di associazione varia tra 1,25 e 3,26×10⁹ M ed il numero di siti varia tra 1,15 e 3,01×10^–10 M.     

Degradation of [3H]thymidine by a pentosyltransferase (EC 2.4.2.4) in the plasma of man and different animals

Summary [³H]Thymidine is degraded by an enzyme (thymidine phosphorylase; EC 2.4.2.4) which we have identified in the plasma of man and some animals. The presence of this enzyme in plasma or sera used to supplement culture media may, under certain experimental conditions, limit the validity of measuring the uptake of radiolabeled thymidine as a means of defining DNA synthesis.Supported in part by United States Public Health Service grant CA-17658 from the National Cancer Institute, and grant RR-05648 from the National Institutes of Health.     

Postmodernity and systems science: An evaluation of J.-L. Le Moigne's contribution to the management of the present civilization

In this text, a French school of systems thought is evaluated with reference to its contribution to postmodernity. The main conclusion is that this system provides some pertinent contribution but that there are also some domains where it does not provide much help. Both these domains are identified and discussed. The text starts with a discussion of the postmodern challenge. This is followed by a presentation and critical evaluation of the theory under consideration. The latter gives rise to the Discussion and Conclusion.     

TLR4 mutations are associated with endotoxin hyporesponsiveness in humans

There is much variability between individuals in the response to inhaled toxins, but it is not known why certain people develop disease when challenged with environmental agents and others remain healthy. To address this, we investigated whether TLR4 (encoding the toll-like receptor-4), which has been shown to affect lipopolysaccharide (LPS) responsiveness in mice, underlies the variability in airway responsiveness to inhaled LPS in humans. Here we show that common, co-segregating missense mutations (Asp299Gly and Thr399Ile) affecting the extracellular domain of the TLR4 receptor are associated with a blunted response to inhaled LPS in humans. Transfection of THP-1 cells demonstrates that the Asp299Gly mutation (but not the Thr399Ile mutation) interrupts TLR4-mediated LPS signalling. Moreover, the wild-type allele of TLR4 rescues the LPS hyporesponsive phenotype in either primary airway epithelial cells or alveolar macrophages obtained from individuals with the TLR4 mutations. Our findings provide the first genetic evidence that common mutations in TLR4 are associated with differences in LPS responsiveness in humans, and demonstrate that gene-sequence changes can alter the ability of the host to respond to environmental stress.