Small molecules as geneticists

Stuart Schreiber and colleagues show how small molecule sensitivities can be used to probe the natural genetic variation present in populations of organisms.     

Ultrastructural chemistry of isolated molecules. Application to biological macromolecules. Study of metachromasia

The ultrastructural chemistry on isolated macromolecules enables to localize chemical function on spread molecules by means of reactions whose product is visible in electron microscopy (metal colloids, lectins, etc.). The reaction of linear polyanions with metachromatic dyes (bifunctional ligands) results in the formation of metachromatic complexes with a periodic structure : ligand molecules are intercalated between the polyanions arranged in parallel arrays; this structure is correlated with the metachromasy.     

Induced metachromasia in bull spermatozoa

Summary The availability of sequential DNA phosphates to bind toluidine blue molecules after acid hydrolysis was studied in normally shaped and misshaped spermatozoa from subfertile and highly fertile bulls. The aim was to associate induced spermatozoal metachromasia with infertility. Some few normally and abnormally shaped cells from highly fertile bulls exhibited an induced metachromasia after being treated with 4N HCl for 10–30 min at 25°C prior to staining. Subfertile bulls contained 12 times as many metachromatic spermatozoa as highly fertile animals. The induced toluidine blue metachromasia is suggested as a rapid and simple method for detecting bull spermatozoa bearing an anomalous DNA-protein complex. This nucleoprotein complex was found to be more frequent in subfertile bulls.     

Small molecules in an RNAi world

In this Opinion, we compare and contrast small molecules and RNAi. We discuss the advantages and disadvantages of both technologies focusing on timing, specificity, dose and therapeutic use.     

Small insecticidal molecules against crop pests

ABSTRACT

Previous decades have seen excessive use of chemical insecticides to control insect-mediated crop losses. However, toxicological and ecological concerns lead to the quest for more sustainable biological molecules as an alternative. Advent of Bt technology witnessed its supersession over chemical control measures and reinvigorated the potential of bioinsecticides as a commercially viable option. But the development of Bt-resistance in insect populations has raised concerns and entails the invention of alternate measures. In this review, we discuss the recent advancements in the field of Bt toxins and evaluate the potential of other insecticidal proteins and RNAi as the next generation insecticidal technologies.     

小分子物质对维持胚胎干细胞未分化状态的调控作用

胚胎干细胞作为一种具有多潜能和高度自我更新能力的种子细胞,己被广泛地应用于医学研究领域。在体外培养条件下,胚胎干细胞可被诱导分化为三个胚层来源的组织细胞,故被看作为最具有应用前景的种子细胞。近年来,对于在体外培养条件下如何维持胚胎干细胞的多能性即使其较长时期的处于未分化状态成为研究热点,其中一些天然存在或人工合成的小分子物质可通过作用于某些特定的靶信号通路,调控胚胎干细胞的分化命运。本文概述了几种小分子物质的最新研究进展,并对小分子物质在成体多分化潜能胚胎样干细胞分化调控方面的应用前景进行评述。     

小RNA分子与精子发生调控

近来研究发现小RNA(small RNAs)可作为转录后及翻译水平上基因表达调节的重要调节因子,利用小RNA来阐明调节精子发生的分子机制取得了显著进展。这些小RNA主要分为3类,即小干扰RNA(siRNA)、微小RNA(miRNA)以及与piwi蛋白相互作用的RNA(piRNA)。在减数分裂和精子发生过程中,小RNA具有多种生物学功能,如利用siRNA体外转染或体内注射来敲低特定基因从而研究该基因在精子发生过程中的作用;miRNA可能参与精子发生中有丝、减数及后减数分裂阶段的基因表达调节;piRNA主要参与调节雄性生殖细胞减数及后减数分裂的过程,在精子发生中起抑制反转录转座子(retrotransposons)的作用。文章对小RNAs合成、作用机制、功能及展望等最新进展进行了综述。     

Small molecules: the lexicon of biodiversity

The extent of microbial diversity in the Biosphere is not known (and probably never will be!). One aspect of this diversity is the production of biologically active small molecules; within the Streptomycetes alone this may be millions of compounds with an extraordinary diversity and complexity of structure. First recognised as pigments and later, in the 1950s, as antibiotics, it is now clear that the small molecules produced by microbes have many different functions in nature. This huge collection of biologically active compounds with various properties has been used as pharmaceuticals and agriculturals. They also interact with proteins and RNA with high specificity and have been shown to be regulators and effectors of diverse biochemical reactions. The use of small molecules (other than as pharmaceuticals) deserves to be explored in order to exploit microbial biotechnology to the full.     

Small molecules with potent osteogenic-inducing activity in osteoblast cells

A chemical screen of 45,000 compounds from a diverse collection led to the identification of two series of small molecules with potent osteogenic activity in mouse MC3T3-E1 osteoblast cells. The first chemical group was characterized by an amino benzothiazole core (AMG0892 series) and the second group by a naphthyl amide core (AMG0309 series). Using alkaline phosphatase (ALP), osteocalcin (OCL) and calcium as markers of osteoblast differentiation and mineralization, both chemical series showed EC₅₀s in the 0.01–0.2 μM range and were consistent for all three markers. Compounds inhibited cell proliferation, had no effect on apoptosis and showed evidence for CREB pathway activity. The present compounds represent some of the most potent osteogenic small molecules reported to date and provide new tools for elucidating signaling mechanisms in osteoblasts.