Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer

CpG island hypermethylation and global genomic hypomethylation are common epigenetic features of cancer cells. Less attention has been focused on histone modifications in cancer cells. We characterized post-translational modifications to histone H4 in a comprehensive panel of normal tissues, cancer cell lines and primary tumors. Using immunodetection, high-performance capillary electrophoresis and mass spectrometry, we found that cancer cells had a loss of monoacetylated and trimethylated forms of histone H4. These changes appeared early and accumulated during the tumorigenic process, as we showed in a mouse model of multistage skin carcinogenesis. The losses occurred predominantly at the acetylated Lys16 and trimethylated Lys20 residues of histone H4 and were associated with the hypomethylation of DNA repetitive sequences, a well-known characteristic of cancer cells. Our data suggest that the global loss of monoacetylation and trimethylation of histone H4 is a common hallmark of human tumor cells.     

Identification of common variants associated with human hippocampal and intracranial volumes

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).     

A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. We mapped FOP to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G --> A; R206H) in the glycine-serine (GS) activation domain of ACVR1, a BMP type I receptor, in all affected individuals examined. Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP.     

Comparative genome sequencing of Escherichia coli allows observation of bacterial evolution on a laboratory timescale

We applied whole-genome resequencing of Escherichia coli to monitor the acquisition and fixation of mutations that conveyed a selective growth advantage during adaptation to a glycerol-based growth medium. We identified 13 different de novo mutations in five different E. coli strains and monitored their fixation over a 44-d period of adaptation. We obtained proof that the observed spontaneous mutations were responsible for improved fitness by creating single, double and triple site-directed mutants that had growth rates matching those of the evolved strains. The success of this new genome-scale approach indicates that real-time evolution studies will now be practical in a wide variety of contexts.     

Modeling and forecasting municipal solid waste generation in the US energy supply

This paper describes an economic and statistical approach to modeling and forecasting municipal solid waste generation in the US energy supply. It begins with a discussion of the historical developments in the waste to energy industry over the last 25 years. Then a model is developed to provide energy policy makers with an analytical framework for understanding the relationships between the solid waste industry and the waste to energy industry. The model is tested empirically using data at the national level. The model's forecasts are compared with projections made by the US Environmental Protection Agency     

A History of the Surrey Institution

The Surrey Institution, Blackfriars, founded in 1808, was, after the Royal Institution and London Institution, the third establishment in London aimed at fostering and disseminating scientific, technical, and literary knowledge and understanding among a wider public. The Institution offered its proprietors and subscribers the use of an extensive reference library and reading rooms and, most importantly, the opportunity to attend courses of lectures on scientific, technological, and other subjects. Though popular in approach, the lectures conformed to high educational standards and were delivered by recognized authorities in their fields. In the Surrey Institution's celebrated auditorium, the 'Rotunda', there appeared over the years such notable scientists as Accum, Thomson, and Gurney on chemistry, Millington, Mason Good, and Woodward on natural philosophy, Bakewell on geology, and Shaw on natural history; literature was brilliantlyrepresented by Coleridge and Hazlitt. During its relatively brief life-span (1808-23)-cut short by financial stringencies-the Surrey Institution provided access to scientific knowledge and thinking to a wide and appreciative audience. As a meeting place fo scientists and men of business with mercantile and manufacturing interests, it performed an important function in cross-fertilizing and reinforcing ideas on innovation and enterprise against the background of the ongoing Industrial Revolution. The present article attempts to supply a historical account, so far lacking, of the foundation, activities and achievements of this significant Institution of the metropolis.     

William Hasledine Pepys FRS: A Life in Scientific Research,Learned Societies and Technical Enterprise

In a long and many-sided career, William Hasledine Pepys (1775-1856) contributed significantly to the advancement of the chemical and physical sciences during the first half of the nineteenth century. As an original investigator he determined, in collaboration with William Allen, the composition of carbon dioxide, and the density of ammonia, and elucidated the chemical phenomena of respiration in man, animals, and plants. The success of these researches was largely due to the use of ingenious apparatus of his own invention and design. In the field of experimental physics, he investigated several aspects of the recently discovered Voltaic electricity: his 'Voltaic coil', consisting of only two plates, but of very large dimensions, was particularly suited for investigating electromagnetic phenomena and was so used in Davy's researches. Pepys was one of the co-founders of the Mineralogical and Geological Societies, and was elected a Fellow of the Royal Society in 1808. As a prominent member of both the Royal and London Institutions, he held honorary office as Manager and Vice-President, contributing materially to the direction of the affairs of these bodies. Pepys was a friend of Humphry Davy and was acquainted with nearly all the leading scientists and medical men of the day. At the same time, he superintended a notable manufacture of surgical instruments in the City, and promoted by his active directorship the affairs of two public companies, both pioneers in their technological fields, namely the Imperial Continental Gas Association, which was active in introducing the new gas illumination to cities and towns across Europe, and the General Steam Navigation Company, which first maintained a regular passenger and cargo service to Continental ports by the exclusive use of steam-propelled vessels. Pepys' advice in scientific and technical matters was widely sought and freely given; he retained his mental powers to the end of his long life, fulfilling his professional commitments until a few days before his death.