The receptors and cells for mammalian taste

The emerging picture of taste coding at the periphery is one of elegant simplicity. Contrary to what was generally believed, it is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes: sweet, sour, bitter, salty and umami. Importantly, receptor cells for each taste quality function as dedicated sensors wired to elicit stereotypic responses.     

Using the fossil record to estimate the age of the last common ancestor of extant primates

Divergence times estimated from molecular data often considerably predate the earliest known fossil representatives of the groups studied. For the order Primates, molecular data calibrated with various external fossil dates uniformly suggest a mid-Cretaceous divergence from other placental mammals, some 90 million years (Myr) ago, whereas the oldest known fossil primates are from the basal Eocene epoch (54-55 Myr ago). The common ancestor of primates should be earlier than the oldest known fossils, but adequate quantification is needed to interpret possible discrepancies between molecular and palaeontological estimates. Here we present a new statistical method, based on an estimate of species preservation derived from a model of the diversification pattern, that suggests a Cretaceous last common ancestor of primates, approximately 81.5 Myr ago, close to the initial divergence time inferred from molecular data. It also suggests that no more than 7% of all primate species that have ever existed are known from fossils. The approach unites all the available palaeontological methods of timing evolutionary events: the fossil record, extant species and clade diversification models.     

Biasing reaction pathways with mechanical force

During the course of chemical reactions, reactant molecules need to surmount an energy barrier to allow their transformation into products. The energy needed for this process is usually provided by heat, light, pressure or electrical potential, which act either by changing the distribution of the reactants on their ground-state potential energy surface or by moving them onto an excited-state potential energy surface and thereby facilitate movement over the energy barrier. A fundamentally different way of initiating or accelerating a reaction is the use of force to deform reacting molecules along a specific direction of the reaction coordinate. Mechanical force has indeed been shown to activate covalent bonds in polymers, but the usual result is chain scission. Here we show that mechanically sensitive chemical groups make it possible to harness the mechanical forces generated when exposing polymer solutions to ultrasound, and that this allows us to accelerate rearrangement reactions and bias reaction pathways to yield products not obtainable from purely thermal or light-induced reactions. We find that when placed within long polymer strands, the trans and cis isomers of a 1,2-disubstituted benzocyclobutene undergo an ultrasound-induced electrocyclic ring opening in a formally conrotatory and formally disrotatory process, respectively, that yield identical products. This contrasts with reaction initiation by light or heat alone, in which case the isomers follow mutually exclusive pathways to different products. Mechanical forces associated with ultrasound can thus clearly alter the shape of potential energy surfaces so that otherwise forbidden or slow processes proceed under mild conditions, with the directionally specific nature of mechanical forces providing a reaction control that is fundamentally different from that achieved by adjusting chemical or physical parameters. Because rearrangement in our system occurs before chain scission, the effect we describe might allow the development of materials that are activated by mechanical stress fields.     

Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia

Chromosomal aberrations are a hallmark of acute lymphoblastic leukaemia (ALL) but alone fail to induce leukaemia. To identify cooperating oncogenic lesions, we performed a genome-wide analysis of leukaemic cells from 242 paediatric ALL patients using high-resolution, single-nucleotide polymorphism arrays and genomic DNA sequencing. Our analyses revealed deletion, amplification, point mutation and structural rearrangement in genes encoding principal regulators of B lymphocyte development and differentiation in 40% of B-progenitor ALL cases. The PAX5 gene was the most frequent target of somatic mutation, being altered in 31.7% of cases. The identified PAX5 mutations resulted in reduced levels of PAX5 protein or the generation of hypomorphic alleles. Deletions were also detected in TCF3 (also known as E2A), EBF1, LEF1, IKZF1 (IKAROS) and IKZF3 (AIOLOS). These findings suggest that direct disruption of pathways controlling B-cell development and differentiation contributes to B-progenitor ALL pathogenesis. Moreover, these data demonstrate the power of high-resolution, genome-wide approaches to identify new molecular lesions in cancer.     

欧拉应用分析于数论研究综述

扼要而又系统地综述了欧拉应用分析于数论研究的早期工作.其中有许多激动人心的数论公式与定理.例如,关于自然数方幂倒数的无穷和公式、关于Zeta函数的欧拉乘积公式、欧拉对4平方数定理的思考与证明,及其欧拉在解决这些问题的同时所创造的有关数论函数、分拆函数和理想数的概念等等.这些概念、定理或公式都是欧拉首先发现并加以精确论证的.与众不同的是,他善于把一个纯数论问题变换为一个分析问题,事实上欧拉的想法更具一般性.它足以展示欧拉的数学工作的深刻与广博.最后我们引述了欧拉发现的数论中几个著名的级数公式和二次互反性定律,它们都是欧拉在数论文库中留给我们的宝贵遗产.