The biological impact of mass-spectrometry-based proteomics

In the past decade, there have been remarkable advances in proteomic technologies. Mass spectrometry has emerged as the preferred method for in-depth characterization of the protein components of biological systems. Using mass spectrometry, key insights into the composition, regulation and function of molecular complexes and pathways have been gained. From these studies, it is clear that mass-spectrometry-based proteomics is now a powerful 'hypothesis-generating engine' that, when combined with complementary molecular, cellular and pharmacological techniques, provides a framework for translating large data sets into an understanding of complex biological processes.     

Identification of protein pheromones that promote aggressive behaviour

Mice use pheromones, compounds emitted and detected by members of the same species, as cues to regulate social behaviours such as pup suckling, aggression and mating. Neurons that detect pheromones are thought to reside in at least two separate organs within the nasal cavity: the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). Each pheromone ligand is thought to activate a dedicated subset of these sensory neurons. However, the nature of the pheromone cues and the identity of the responding neurons that regulate specific social behaviours are largely unknown. Here we show, by direct activation of sensory neurons and analysis of behaviour, that at least two chemically distinct ligands are sufficient to promote male-male aggression and stimulate VNO neurons. We have purified and analysed one of these classes of ligand and found its specific aggression-promoting activity to be dependent on the presence of the protein component of the major urinary protein (MUP) complex, which is known to comprise specialized lipocalin proteins bound to small organic molecules. Using calcium imaging of dissociated vomeronasal neurons (VNs), we have determined that the MUP protein activates a sensory neuron subfamily characterized by the expression of the G-protein Galpha(o) subunit (also known as Gnao) and Vmn2r putative pheromone receptors (V2Rs). Genomic analysis indicates species-specific co-expansions of MUPs and V2Rs, as would be expected among pheromone-signalling components. Finally, we show that the aggressive behaviour induced by the MUPs occurs exclusively through VNO neuronal circuits. Our results substantiate the idea of MUP proteins as pheromone ligands that mediate male-male aggression through the accessory olfactory neural pathway.     

Transformation of spin information into large electrical signals using carbon nanotubes

Spin electronics (spintronics) exploits the magnetic nature of electrons, and this principle is commercially applied in, for example, the spin valves of disk-drive read heads. There is currently widespread interest in developing new types of spintronic devices based on industrially relevant semiconductors, in which a spin-polarized current flows through a lateral channel between a spin-polarized source and drain. However, the transformation of spin information into large electrical signals is limited by spin relaxation, so that the magnetoresistive signals are below 1% (ref. 2). Here we report large magnetoresistance effects (61% at 5 K), which correspond to large output signals (65 mV), in devices where the non-magnetic channel is a multiwall carbon nanotube that spans a 1.5 microm gap between epitaxial electrodes of the highly spin polarized manganite La(0.7)Sr(0.3)MnO3. This spintronic system combines a number of favourable properties that enable this performance; the long spin lifetime in nanotubes due to the small spin-orbit coupling of carbon; the high Fermi velocity in nanotubes that limits the carrier dwell time; the high spin polarization in the manganite electrodes, which remains high right up to the manganite-nanotube interface; and the resistance of the interfacial barrier for spin injection. We support these conclusions regarding the interface using density functional theory calculations. The success of our experiments with such chemically and geometrically different materials should inspire new avenues in materials selection for future spintronics applications.     

The systematics of Crotaphytus wislizeni, the leopard lizards. Part III. the leopard lizards of the Great Basin and adjoining areas, with a description of a new subspecies from the Lahontan Basin

Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 st1\:*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} A general analysis of the populations of Crotaphytus wislizeni in the Great Basin is presented. A new subspecies, C. wislizeni maculosus, for the Lahontan Basin, Nevada, is described and comparisons of color pattern, some scale patterns, and skull measurements are presented.     

Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles

Trans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell type-specific cis and trans expression quantitative trait loci (eQTLs), including multi-locus trans associations to LYZ and KLF4 in monocytes and B cells, respectively. Additionally, we observe a B cell-specific trans association of rs11171739 at 12q13.2, a known autoimmune disease locus, with IP6K2 (P = 5.8 × 10(-15)), PRIC285 (P = 3.0 × 10(-10)) and an upstream region of CDKN1A (P = 2 × 10(-52)), suggesting roles for cell cycle regulation and peroxisome proliferator-activated receptor γ (PPARγ) signaling in autoimmune pathogenesis. We also find that specific human leukocyte antigen (HLA) alleles form trans associations with the expression of AOAH and ARHGAP24 in monocytes but not in B cells. In summary, we show that mapping gene expression in defined primary cell populations identifies new cell type-specific trans-regulated networks and provides insights into the genetic basis of disease susceptibility.