A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL)

The importance of individual microRNAs (miRNAs) has been established in specific cancers. However, a comprehensive analysis of the contribution of miRNAs to the pathogenesis of any specific cancer is lacking. Here we show that in T-cell acute lymphoblastic leukemia (T-ALL), a small set of miRNAs is responsible for the cooperative suppression of several tumor suppressor genes. Cross-comparison of miRNA expression profiles in human T-ALL with the results of an unbiased miRNA library screen allowed us to identify five miRNAs (miR-19b, miR-20a, miR-26a, miR-92 and miR-223) that are capable of promoting T-ALL development in a mouse model and which account for the majority of miRNA expression in human T-ALL. Moreover, these miRNAs produce overlapping and cooperative effects on tumor suppressor genes implicated in the pathogenesis of T-ALL, including IKAROS (also known as IKZF1), PTEN, BIM, PHF6, NF1 and FBXW7. Thus, a comprehensive and unbiased analysis of miRNA action in T-ALL reveals a striking pattern of miRNA-tumor suppressor gene interactions in this cancer.     

Insect olfactory receptors are heteromeric ligand-gated ion channels

In insects, each olfactory sensory neuron expresses between one and three ligand-binding members of the olfactory receptor (OR) gene family, along with the highly conserved and broadly expressed Or83b co-receptor. The functional insect OR consists of a heteromeric complex of unknown stoichiometry but comprising at least one variable odorant-binding subunit and one constant Or83b family subunit. Insect ORs lack homology to G-protein-coupled chemosensory receptors in vertebrates and possess a distinct seven-transmembrane topology with the amino terminus located intracellularly. Here we provide evidence that heteromeric insect ORs comprise a new class of ligand-activated non-selective cation channels. Heterologous cells expressing silkmoth, fruitfly or mosquito heteromeric OR complexes showed extracellular Ca2+ influx and cation-non-selective ion conductance on stimulation with odorant. Odour-evoked OR currents are independent of known G-protein-coupled second messenger pathways. The fast response kinetics and OR-subunit-dependent K+ ion selectivity of the insect OR complex support the hypothesis that the complex between OR and Or83b itself confers channel activity. Direct evidence for odorant-gated channels was obtained by outside-out patch-clamp recording of Xenopus oocyte and HEK293T cell membranes expressing insect OR complexes. The ligand-gated ion channel formed by an insect OR complex seems to be the basis for a unique strategy that insects have acquired to respond to the olfactory environment.     

Influence of soil water availability on competition among leafy spurge ( Euphorbia Esula ) and grasses

Some perturbations differentially influence invasive plant and grass production. For example, growth regulator herbicides and biological control agents can dramatically reduce leafy spurge production while having little or no influence on grass production, and overgrazing can reduce grass production while not substantially influencing leafy spurge production because cattle typically ingest little or no leafy spurge. To predict how grass production will respond to a perturbation that influences only leafy spurge and to predict how leafy spurge production will respond to a perturbation that affects only grasses, competitive relationships must be understood. Seeding mixtures of leafy spurge and 2 grasses were planted in experiments and grown for 127 days to determine whether different water application regimes influenced competition among these 3 species. Competition became less intense as the number of water applications increased. If this finding holds true under field conditions, then it indicates that competition is less intense in years and locations with numerous precipitation events. Competitive interactions (i.e., competition coefficients) were less variable when water was applied more frequently, but the ability of models to account for variation in plant weight (i.e., r 2 ) was not influenced by the frequency of water application. This suggests that models will predict invasive plant and grass biomass with equal accuracy in years with few or many precipitation events. Competitive effects were similar regardless of grass species, which suggests that grasses might be considered collectively in predicting response to perturbations in the field.     

Geographic variation in pelage color of pi?on mice ( Peromyscus truei ) in the northern Great Basin and environs

Cluster analyses of values for hue, value, and chroma (based on Munsell soil-color charts) obtained at 6 points on pelages of 202 adult pion mice ( Peromyscus truei ) from the northern Great Basin and environs produced dendrograms with specimens grouped into 5 clusters. In most instances distribution of specimens forming clusters reflected those published for nominal races. In instances in which previous distributions of nominal races were not supported and for specimens previously unclassified, geographic distribution of groups of color morphs was logical and suggested avenues for additional research on geographic variation in the species.     

The case for open computer programs

Scientific communication relies on evidence that cannot be entirely included in publications, but the rise of computational science has added a new layer of inaccessibility. Although it is now accepted that data should be made available on request, the current regulations regarding the availability of software are inconsistent. We argue that, with some exceptions, anything less than the release of source programs is intolerable for results that depend on computation. The vagaries of hardware, software and natural language will always ensure that exact reproducibility remains uncertain, but withholding code increases the chances that efforts to reproduce results will fail.     

Wnt-Ryk signalling mediates medial-lateral retinotectal topographic mapping

Computational modelling has suggested that at least two counteracting forces are required for establishing topographic maps. Ephrin-family proteins are required for both anterior-posterior and medial-lateral topographic mapping, but the opposing forces have not been well characterized. Wnt-family proteins are recently discovered axon guidance cues. We find that Wnt3 is expressed in a medial-lateral decreasing gradient in chick optic tectum and mouse superior colliculus. Retinal ganglion cell (RGC) axons from different dorsal-ventral positions showed graded and biphasic response to Wnt3 in a concentration-dependent manner. Wnt3 repulsion is mediated by Ryk, expressed in a ventral-to-dorsal decreasing gradient, whereas attraction of dorsal axons at lower Wnt3 concentrations is mediated by Frizzled(s). Overexpression of Wnt3 in the lateral tectum repelled the termination zones of dorsal RGC axons in vivo. Expression of a dominant-negative Ryk in dorsal RGC axons caused a medial shift of the termination zones, promoting medially directed interstitial branches and eliminating laterally directed branches. Therefore, a classical morphogen, Wnt3, acting as an axon guidance molecule, plays a role in retinotectal mapping along the medial-lateral axis, counterbalancing the medial-directed EphrinB1-EphB activity.     

Spontaneous symmetry breaking in a quenched ferromagnetic spinor Bose-Einstein condensate

A central goal in condensed matter and modern atomic physics is the exploration of quantum phases of matter--in particular, how the universal characteristics of zero-temperature quantum phase transitions differ from those established for thermal phase transitions at non-zero temperature. Compared to conventional condensed matter systems, atomic gases provide a unique opportunity to explore quantum dynamics far from equilibrium. For example, gaseous spinor Bose-Einstein condensates (whose atoms have non-zero internal angular momentum) are quantum fluids that simultaneously realize superfluidity and magnetism, both of which are associated with symmetry breaking. Here we explore spontaneous symmetry breaking in 87Rb spinor condensates, rapidly quenched across a quantum phase transition to a ferromagnetic state. We observe the formation of spin textures, ferromagnetic domains and domain walls, and demonstrate phase-sensitive in situ detection of spin vortices. The latter are topological defects resulting from the symmetry breaking, containing non-zero spin current but no net mass current.     

Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1.

The underlying causes of obesity are poorly understood but probably involve complex interactions between many neurotransmitter and neuropeptide systems involved in the regulation of food intake and energy balance. Three pieces of evidence indicate that the neuropeptide melanin-concentrating hormone (MCH) is an important component of this system. First, MCH stimulates feeding when injected directly into rat brains; second, the messenger RNA for the MCH precursor is upregulated in the hypothalamus of genetically obese mice and in fasted animals; and third, mice lacking MCH eat less and are lean. MCH antagonists might, therefore, provide a treatment for obesity. However, the development of such molecules has been hampered because the identity of the MCH receptor has been unknown until now. Here we show that the 353-amino-acid human orphan G-protein-coupled receptor SLC-1 expressed in HEK293 cells binds MCH with sub-nanomolar affinity, and is stimulated by MCH to mobilize intracellular Ca2+ and reduce forskolin-elevated cyclic AMP levels. We also show that SLC-1 messenger RNA and protein is expressed in the ventromedial and dorsomedial nuclei of the hypothalamus, consistent with a role for SLC-1 in mediating the effects of MCH on feeding.     

论专家证人渎职责任

在传统的做法中，基于证人豁免原则的保护，作为专家证人出庭作证的专业人士在审判中所提供的证言不受追究。而专家证人玩忽职守责任的理论又非常具有说服力，因此在实际中，出现了对传统的背离。一种关于专家证人渎职责任的理论可能正在形成。