Portrait of a molecule

The double helix is idealized for its aesthetic elegant structure, but the reality of DNA's physical existence is quite different. Most DNA in the cell is compressed into a tangled package that somehow still exposes itself to meticulous gene-regulatory control. Philip Ball holds a mirror up to what we truly know about the mysteries of DNA's life inside a cell.     

Spatial proximity of translocation-prone gene loci in human lymphomas

Cancer cells frequently have disease-specific chromosome rearrangements. It is poorly understood why translocations between chromosomes recur at specific breakpoints in the genome. Here we provide evidence that higher-order spatial genome organization is a contributing factor in the formation of recurrent translocations. We show that MYC, BCL and immunoglobulin loci, which are recurrently translocated in various B-cell lymphomas, are preferentially positioned in close spatial proximity relative to each other in normal B cells. Loci in spatial proximity are non-randomly positioned towards the nuclear interior in normal B cells. This locus proximity is the consequence of higher-order genome structure rather than a property of individual genes. Our results suggest that the formation of specific translocations in human lymphomas, and perhaps other tissues, is determined in part by higher-order spatial organization of the genome.     

A defective response to Hedgehog signaling in disorders of cholesterol biosynthesis

Smith-Lemli-Opitz syndrome (SLOS), desmosterolosis and lathosterolosis are human syndromes caused by defects in the final stages of cholesterol biosynthesis. Many of the developmental malformations in these syndromes occur in tissues and structures whose embryonic patterning depends on signaling by the Hedgehog (Hh) family of secreted proteins. Here we report that response to the Hh signal is compromised in mutant cells from mouse models of SLOS and lathosterolosis and in normal cells pharmacologically depleted of sterols. We show that decreasing levels of cellular sterols correlate with diminishing responsiveness to the Hh signal. This diminished response occurs at sterol levels sufficient for normal autoprocessing of Hh protein, which requires cholesterol as cofactor and covalent adduct. We further find that sterol depletion affects the activity of Smoothened (Smo), an essential component of the Hh signal transduction apparatus.     

Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy

Digital clubbing, recognized by Hippocrates in the fifth century BC, is the outward hallmark of pulmonary hypertrophic osteoarthropathy, a clinical constellation that develops secondary to various acquired diseases, especially intrathoracic neoplasm. The pathogenesis of clubbing and hypertrophic osteoarthropathy has hitherto been poorly understood, but a clinically indistinguishable primary (idiopathic) form of hypertrophic osteoarthropathy (PHO) is recognized. This familial disorder can cause diagnostic confusion, as well as significant disability. By autozygosity methods, we mapped PHO to chromosome 4q33-q34 and identified mutations in HPGD, encoding 15-hydroxyprostaglandin dehydrogenase, the main enzyme of prostaglandin degradation. Homozygous individuals develop PHO secondary to chronically elevated prostaglandin E(2) levels. Heterozygous relatives also show milder biochemical and clinical manifestations. These findings not only suggest therapies for PHO, but also imply that clubbing secondary to other pathologies may be prostaglandin mediated. Testing for HPGD mutations and biochemical testing for HPGD deficiency in patients with unexplained clubbing might help to obviate extensive searches for occult pathology.     

SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout

Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200-500 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.     

从服务中心到战略推动者:香港中文大学信息化建设的未来展望

香港中文大学历经半个世纪风雨,如今已发展成为世界知名研究型大学.与此同时,计算机和网络技术的日新月异,极大地改变着人们的生活、学习、工作和社交模式,也给大学提出了源源不断的新挑战.如今,IT已不再是实验室里高高在上的尖端科技,而是维持社会正常运作的基础设施和服务,并且拥有着巨大的潜力给生活带来更多的智慧.作为高等教育的IT部门,如何应对这业务格局的转变,如何了解和满足用户日益提升的服务需求,如何发挥IT技术的价值以推动大学战略发展,都是我们应当考虑的问题.本文将介绍香港中文大学的信息化管理与发展现状,讨论当前遇到的问题并分析应对方法,探索为实现大学信息化战略推动者之愿景应选择的未来道路.     

超冷的水

又发现了两种新水。要是没有水，我们原本不会来到这个世界。水的热容量在-45℃时应该变成无穷大。水的其它特性似乎也变得一团糟，就像水经历了某种灾变一样，为什么？如果想象在太平洋之下11公里处的马里亚那海沟中即在海洋最深之处的高压之下，人还能生活，便会看到这是一个寂静的、永远黑暗的世界，压力高达1000个大气压。那是一座相当于洋底每平方米承受1000吨压力的海水之增。在如此恶劣的条件下，生存必定不易。然而现在有些物理学家相信在这样高的压力下甚至水本身可能也难于保持不变。他们认为如果在以上压力下水若能保持不变即仍…