Biological properties of a CD4 immunoadhesin

Molecular fusions of CD4, the receptor for human immunodeficiency virus (HIV), with immunoglobulin (termed CD4 immunoadhesins) possess both the gp120-binding and HIV-blocking properties of recombinant soluble CD4, and certain properties of IgG, notably long plasma half-life and Fc receptor binding. Here we show that a CD4 immunoadhesin can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) towards HIV-infected cells, although, unlike natural anti-gp120 antibodies, it does not allow ADCC towards uninfected CD4-expressing cells that have bound soluble gp120 to the CD4 on their surface. In addition, CD4 immunoadhesin, like natural IgG molecules, is efficiently transferred across the placenta of a primate. These observations have implications for the therapeutic application of CD4 immunoadhesins, particularly in the area of perinatal transmission of HIV infection.     

Addition of human melanopsin renders mammalian cells photoresponsive

A small number of mammalian retinal ganglion cells act as photoreceptors for regulating certain non-image forming photoresponses. These intrinsically photosensitive retinal ganglion cells express the putative photopigment melanopsin. Ablation of the melanopsin gene renders these cells insensitive to light; however, the precise role of melanopsin in supporting cellular photosensitivity is unconfirmed. Here we show that heterologous expression of human melanopsin in a mouse paraneuronal cell line (Neuro-2a) is sufficient to render these cells photoreceptive. Under such conditions, melanopsin acts as a sensory photopigment, coupled to a native ion channel via a G-protein signalling cascade, to drive physiological light detection. The melanopsin photoresponse relies on the presence of cis-isoforms of retinaldehyde and is selectively sensitive to short-wavelength light. We also present evidence to show that melanopsin functions as a bistable pigment in this system, having an intrinsic photoisomerase regeneration function that is chromatically shifted to longer wavelengths.     

A circumstellar disk associated with a massive protostellar object

The formation process for stars with masses several times that of the Sun is still unclear. The two main theories are mergers of several low-mass young stellar objects, which requires a high stellar density, or mass accretion from circumstellar disks in the same way as low-mass stars are formed, accompanied by outflows during the process of gravitational infall. Although a number of disks have been discovered around low- and intermediate-mass young stellar objects, the presence of disks around massive young stellar objects is still uncertain and the mass of the disk system detected around one such object, M17, is disputed. Here we report near-infrared imaging polarimetry that reveals an outflow/disk system around the Becklin-Neugebauer protostellar object, which has a mass of at least seven solar masses (M(o)). This strongly supports the theory that stars with masses of at least 7M(o) form in the same way as lower mass stars.     

Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor

Neuropeptide Y (NPY) is believed to exert antinociceptive actions by inhibiting the release of substance P and other 'pain neurotransmitters' in the spinal cord dorsal horn. However, the physiological significance and potential therapeutic value of NPY remain obscure. It is also unclear which receptor subtype(s) are involved. To identify a possible physiological role for the NPY Y1 receptor in pain transmission, we generated NPY Y1 receptor null mutant (Y1-/-) mice by homologous recombination techniques. Here we show that Y1-/- mice develop hyperalgesia to acute thermal, cutaneous and visceral chemical pain, and exhibit mechanical hypersensitivity. Neuropathic pain is increased, and the mice show a complete absence of the pharmacological analgesic effects of NPY. In the periphery, Y1 receptor activation is sufficient and required for substance P release and the subsequent development of neurogenic inflammation and plasma leakage. We conclude that the Y1 receptor is required for central physiological and pharmacological NPY-induced analgesia and that its activation is both sufficient and required for the release of substance P and initiation of neurogenic inflammation.     

Ecological importance of trichromatic vision to primates

Trichromatic colour vision, characterized by three retinal photopigments tuned to peak wavelengths of approximately 430 nm, approximately 535 nm and approximately 562 nm (refs 1, 2), has evolved convergently in catarrhine primates and one genus of New World monkey, the howlers (genus Alouatta). This uniform capacity to discriminate red-green colours, which is not found in other mammals, has been proposed as advantageous for the long-range detection of either ripe fruits or young leaves (which frequently flush red in the tropics) against a background of mature foliage. Here we show that four trichromatic primate species in Kibale Forest, Uganda, eat leaves that are colour discriminated only by red-greenness, a colour axis correlated with high protein levels and low toughness. Despite their divergent digestive systems, these primates have no significant interspecific differences in leaf colour selection. In contrast, eaten fruits were generally discriminated from mature leaves on both red-green and yellow-blue channels and also by their luminance, with a significant difference between chimpanzees and monkeys in fruit colour choice. Our results implicate leaf consumption, a critical food resource when fruit is scarce, as having unique value in maintaining trichromacy in catarrhines.     

What are universities for?

Governments worldwide rightly regard universities as fundamental to the achievement of many national priorities. But it is the paper’s contention that many misunderstand their true benefit to society. Investments in universities are increasingly based on the belief that the science labs in particular of research-intensive universities can be the source of a continuous stream of people and ideas that will spawn innovative and fast growing companies to form the nexus of the knowledge-based economy. This belief is a source of misconceived policies that offer only ultimate disillusion. It is the totality of the university enterprise that is important, as the only place where that totality of ourselves and our world is brought together, and which makes it the strongest provider of the rational explanation and meaning that societies need. In research, universities create new possibilities; in teaching, they shape new people. Its graduates learn to seek the true meaning of things: to distinguish between the true and the merely seemingly true, to verify for themselves what is stable in that very unstable compound that often passes for knowledge. It is the complex, interacting whole of the university that is the source of the separate economic, social, cultural and utilitarian benefits valued by society. It needs to be understood, valued and managed as a whole. These perceptions are a direct challenge to not only to governments but to university administrators who have been either cowed or seduced into the slipshod thinking that is leading to demands that universities cannot satisfy, whilst obscuring their most important contributions. The challenge to both is to permit autonomy without oppressive accountability, and to give staff and students the freedom to think, speculate and research. These are the very conditions of the personal and collective creativity that are the sources of a university’s deepest benefits to its society.