Association of the jets of Enceladus with the warmest regions on its south-polar fractures

Jets of material have been seen emanating from the south-polar terrain of Saturn's satellite Enceladus. Observations have shown that this region is anomalously warm, with the hottest measured temperatures coinciding with the four 'tiger stripe' fractures, named Alexandria, Cairo, Baghdad and Damascus, that straddle the region. Here we use Cassini images taken from a variety of viewing directions over two years to triangulate the source locations for the most prominent jets, and compare these with the infrared hotspot locations and the predictions from a recent model of tidally induced shear heating within the fractures. We find that the jets emanate from the four tiger stripes, with the strongest sources on Baghdad and Damascus. All the jets from each fracture seem to lie in the same nearly vertical plane. There is a strong spatial coincidence between our geographical sources and the locations of increased temperature revealed by the infrared experiment. Comparison with the shear heating model shows broad agreement; the exception is the prediction that Baghdad is the least active lineament, whereas we find it to be the most active. We predict that several new hotspots remain to be discovered by future thermal observations.     

A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse

In horses, graying with age is an autosomal dominant trait associated with a high incidence of melanoma and vitiligo-like depigmentation. Here we show that the Gray phenotype is caused by a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation. Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses. Gray horses carrying a loss-of-function mutation in ASIP (agouti signaling protein) had a higher incidence of melanoma, implying that increased melanocortin-1 receptor signaling promotes melanoma development in Gray horses. The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals.     

TCR signaling requirements for activating T cells and for generating memory

Over the last two decades the molecular and cellular mechanisms underlying T cell activation, expansion, differentiation, and memory formation have been intensively investigated. These studies revealed that the generation of memory T cells is critically impacted by a number of factors, including the magnitude of the inflammatory response and cytokine production, the type of dendritic cell [DC] that presents the pathogen derived antigen, their maturation status, and the concomitant provision of costimulation. Nevertheless, the primary stimulus leading to T cell activation is generated through the T cell receptor [TCR] following its engagement with a peptide MHC ligand [pMHC]. The purpose of this review is to highlight classical and recent findings on how antigen recognition, the degree of TCR stimulation, and intracellular signal transduction pathways impact the formation of effector and memory T cells.     

Chemical remodelling of cell surfaces in living animals

Cell surfaces are endowed with biological functionality designed to mediate extracellular communication. The cell-surface repertoire can be expanded to include abiotic functionality through the biosynthetic introduction of unnatural sugars into cellular glycans, a process termed metabolic oligosaccharide engineering. This technique has been exploited in fundamental studies of glycan-dependent cell-cell and virus-cell interactions and also provides an avenue for the chemical remodelling of living cells. Unique chemical functional groups can be delivered to cell-surface glycans by metabolism of the corresponding unnatural precursor sugars. These functional groups can then undergo covalent reaction with exogenous agents bearing complementary functionality. The exquisite chemical selectivity required of this process is supplied by the Staudinger ligation of azides and phosphines, a reaction that has been performed on cultured cells without detriment to their physiology. Here we demonstrate that the Staudinger ligation can be executed in living animals, enabling the chemical modification of cells within their native environment. The ability to tag cell-surface glycans in vivo may enable therapeutic targeting and non-invasive imaging of changes in glycosylation during disease progression.     

Increased relative growth rate of normal rat cells in vitro with crocetin

Summary The carotenoid crocetin (earlier found to increase relative growth of Walker 256 tumor cells and their radiosensitivity), is shown to increase the relative growth of normal Sprague-Dawley rat muscle derived cells in vitro, presumably by increasing oxygen transport.     

The high activity of fluorohydroxybenzylbenzimidazoles against some small RNA-viruses

Zusammenfassung Fluorierte Derivate des 2-(-Oxybenzyl)-benzimidazol hemmen die Vermehrung des Poliovirus, 1, 2 und 3, sowie diejenige des Coxsackievirus A9 und A21.     

Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites

Inhibitory neurotransmission mediated by GABA(A) receptors can be modulated by the endogenous neurosteroids, allopregnanolone and tetrahydro-deoxycorticosterone. Neurosteroids are synthesized de novo in the brain during stress, pregnancyand after ethanol consumption, and disrupted steroid regulation of GABAergic transmission is strongly implicated in several debilitating conditions such as panic disorder, major depression, schizophrenia, alcohol dependence and catamenial epilepsy. Determining how neurosteroids interact with the GABA(A) receptor is a prerequisite for understanding their physiological and pathophysiological roles in the brain. Here we identify two discrete binding sites in the receptor's transmembrane domains that mediate the potentiating and direct activation effects of neurosteroids. They potentiate GABA responses from a cavity formed by the alpha-subunit transmembrane domains, whereas direct receptor activation is initiated by interfacial residues between alpha and beta subunits and is enhanced by steroid binding to the potentiation site. Thus, significant receptor activation by neurosteroids relies on occupancy of both the activation and potentiation sites. These sites are highly conserved throughout the GABA(A )receptor family, and their identification provides a unique opportunity for the development of new therapeutic, neurosteroid-based ligands and transgenic disease models of neurosteroid dysfunction.