Structure of an SH2 domain of the p85 alpha subunit of phosphatidylinositol-3-OH kinase.

Receptor protein-tyrosine kinases, through phosphorylation of specific tyrosine residues, generate high-affinity binding sites which direct assembly of multienzyme signalling complexes. Many of these signalling proteins, including phospholipase C gamma, GTPase-activating protein and phosphatidylinositol-3-OH kinase, contain src-homology 2 (SH2) domains, which bind with high affinity and specificity to tyrosine-phosphorylated sequences. The critical role played by SH2 domains in signalling has been highlighted by recent studies showing that mutation of specific phosphorylation sites on the platelet-derived growth factor receptor impair its association with phosphatidylinositol-3-OH kinase, preventing growth factor-induced mitogenesis. Here we report the solution structure of an isolated SH2 domain from the 85K regulatory subunit of phosphatidylinositol-3-OH kinase, determined using multidimensional nuclear magnetic resonance spectroscopy. The structure is characterized by a central region of beta-sheet flanked by two alpha-helices, with a highly flexible loop close to functionally important residues previously identified by site-directed mutagenesis.     

Room-temperature solid-state maser

The invention of the laser has resulted in many innovations, and the device has become ubiquitous. However, the maser, which amplifies microwave radiation rather than visible light, has not had as large an impact, despite being instrumental in the laser's birth. The maser's relative obscurity has mainly been due to the inconvenience of the operating conditions needed for its various realizations: atomic and free-electron masers require vacuum chambers and pumping; and solid-state masers, although they excel as low-noise amplifiers and are occasionally incorporated in ultrastable oscillators, typically require cryogenic refrigeration. Most realizations of masers also require strong magnets, magnetic shielding or both. Overcoming these various obstacles would pave the way for improvements such as more-sensitive chemical assays, more-precise determinations of biomolecular structure and function, and more-accurate medical diagnostics (including tomography) based on enhanced magnetic resonance spectrometers incorporating maser amplifiers and oscillators. Here we report the experimental demonstration of a solid-state maser operating at room temperature in pulsed mode. It works on a laboratory bench, in air, in the terrestrial magnetic field and amplifies at around 1.45 gigahertz. In contrast to the cryogenic ruby maser, in our maser the gain medium is an organic mixed molecular crystal, p-terphenyl doped with pentacene, the latter being photo-excited by yellow light. The maser's pumping mechanism exploits spin-selective molecular intersystem crossing into pentacene's triplet ground state. When configured as an oscillator, the solid-state maser's measured output power of around -10 decibel milliwatts is approximately 100 million times greater than that of an atomic hydrogen maser, which oscillates at a similar frequency (about 1.42 gigahertz). By exploiting the high levels of spin polarization readily generated by intersystem crossing in photo-excited pentacene and other aromatic molecules, this new type of maser seems to be capable of amplifying with a residual noise temperature far below room temperature.     

Relaxin affects the central control of oxytocin release

In several species the myometrium is quiescent shortly before parturition. At this time high titres of relaxin are present in the plasma and there is evidence that the hormone has a direct inhibitory action on the uterine muscle. Relaxin could also contribute to uterine quiescence by inhibiting oxytocin release. To determine whether relaxin has a central action on the release of oxytocin, we have studied the effect of intravenous injections of porcine relaxin on milk ejection in the anaesthetized lactating rat. We report that reflex milk ejection was suppressed by relaxin in a dose-dependent manner, the onset of inhibition being rapid and lasting from 10 to 60 min. After the period of inhibition the normal temporal pattern of reflex milk ejection was resumed. Mammary sensitivity to exogenous or endogenous oxytocin was reduced by relaxin but not sufficiently to explain the effects observed. Furthermore, relaxin (1 microgram per rat) injected into the cerebral ventricles profoundly disturbed the pattern of reflex milk ejection without affecting the response of the mammary gland to oxytocin. These results suggest a novel role for relaxin within the central nervous system. The site in the brain at which the effects of relaxin are exerted remains unknown.