Science Progress

Allergy, auto immunity and cancer are becoming more prevalent in the developed world. One explanation might be that the immune system required to protect us from such problems is being inadequately trained, perhaps due to our increased separation from the environment which has shaped our mutating genes since we emerged from the primaeval ooze. Those infections which were the essential primers of our immunity are being prevented and action is needed to refocus the immune response without exposing us to the diseases of the past. In this paper we assess our place in relation to the environment and consider ways in which the situation can be redressed. There are considerable similarities between the immune system and human consciousness. Both enter the world in considerable ignorance of the events awaiting them, yet with the genetic ability, endowed by millennia of selection and evolution, to experience the world, to interpret and act on the experiences and to retain memory of the experiences. In both systems, maternal influences and early environmental encounters have profound effects on determining the patterns of subsequent responses. Ideally the ‘learned’ responses will benefit or protect the individual but inappropriate responses may lead to self damage. As the environment has altered irrevocably, attention must be paid to regulating the balance of immunological responsiveness to that expected of the normal immunological learning process. This should be possible by novel vaccination strategies.

A special family of inhibitors, known as the serpins, has evolved an extraordinary mechanism to enable the control of the proteolytic pathways essential to life. The serpins undergo a profound change in conformation to entrap their target protease in an irreversible complex. The solving of the structure of this complex now completes a video depiction of the changes involved. The serpin, just like a mousetrap, is seen to change with a springlike movement from an initial metastable state to a final hyperstable form. The structure shows how this conformational shift not only inhibits the protease but also destroys it. A bonus from these structural insights is the realisation that a number of diseases, as diverse as thrombosis, cirrhosis and dementia, all share a common mechanism arising from similar mutations of different serpins.

Photochromic reactions of 2H-benzopyrans have been extensively studied to design new materials for commercial applications such as optical memories. Photochromism of 2H-benzopyrans proceeds from a C–O bond cleavage of the colorless closed form to give the colored open forms, which can thermally revert back to the original closed form. From time-resolved absorption spectroscopy, the ring opening of 2H-benzopyrans, 2,4-diphenyl-and 2,2,4-triphenyl-2H-benzopyran, is found to occur via the excited singlet state within 2 ps to produce vibrationally excited open forms in the ground electronic state. In the subnanosecond to submillisecond time domain, several decay components are observed. These components are assigned to respective stereoisomers with respect to two double bonds and one single bond of the open enone forms. As revealed from pump-laser power dependencies of the yields of the open forms, the photocleavage of the benzopyran molecules gives at first only the open forms revertible to the closed form by a single-bond rotation, and the photoexcitation of the first generated open forms gives rise to other open forms that need a double-bond rotation for reversion to the original closed form. Such a two-step two-photon photochromism can be expected to have a wide range of application.