Electrostatic trapping of ammonia molecules

The ability to cool and slow atoms with light for subsequent trapping allows investigations of the properties and interactions of the trapped atoms in unprecedented detail. By contrast, the complex structure of molecules prohibits this type of manipulation, but magnetic trapping of calcium hydride molecules thermalized in ultra-cold buffer gas and optical trapping of caesium dimers generated from ultra-cold caesium atoms have been reported. However, these methods depend on the target molecules being paramagnetic or able to form through the association of atoms amenable to laser cooling, respectively, thus restricting the range of species that can be studied. Here we describe the slowing of an adiabatically cooled beam of deuterated ammonia molecules by time-varying inhomogeneous electric fields and subsequent loading into an electrostatic trap. We are able to trap state-selected ammonia molecules with a density of 10(6) cm(-3) in a volume of 0.25 cm3 at temperatures below 0.35 K. We observe pronounced density oscillations caused by the rapid switching of the electric fields during loading of the trap. Our findings illustrate that polar molecules can be efficiently cooled and trapped, thus providing an opportunity to study collisions and collective quantum effects in a wide range of ultra-cold molecular systems.     

Haem homeostasis is regulated by the conserved and concerted functions of HRG-1 proteins

Haems are metalloporphyrins that serve as prosthetic groups for various biological processes including respiration, gas sensing, xenobiotic detoxification, cell differentiation, circadian clock control, metabolic reprogramming and microRNA processing. With a few exceptions, haem is synthesized by a multistep biosynthetic pathway comprising defined intermediates that are highly conserved throughout evolution. Despite our extensive knowledge of haem biosynthesis and degradation, the cellular pathways and molecules that mediate intracellular haem trafficking are unknown. The experimental setback in identifying haem trafficking pathways has been the inability to dissociate the highly regulated cellular synthesis and degradation of haem from intracellular trafficking events. Caenorhabditis elegans and related helminths are natural haem auxotrophs that acquire environmental haem for incorporation into haemoproteins, which have vertebrate orthologues. Here we show, by exploiting this auxotrophy to identify HRG-1 proteins in C. elegans, that these proteins are essential for haem homeostasis and normal development in worms and vertebrates. Depletion of hrg-1, or its paralogue hrg-4, in worms results in the disruption of organismal haem sensing and an abnormal response to haem analogues. HRG-1 and HRG-4 are previously unknown transmembrane proteins, which reside in distinct intracellular compartments. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations and, most strikingly, profound defects in erythropoiesis-phenotypes that are fully rescued by worm HRG-1. Human and worm proteins localize together, and bind and transport haem, thus establishing an evolutionarily conserved function for HRG-1. These findings reveal conserved pathways for cellular haem trafficking in animals that define the model for eukaryotic haem transport. Thus, uncovering the mechanisms of haem transport in C. elegans may provide insights into human disorders of haem metabolism and reveal new drug targets for developing anthelminthics to combat worm infestations.     

Evaluation and characterization of an endosperm-specific sbeⅡa promoter in wheat

Starch,the main component of the wheat grain,is the product of a complex biochemical pathway. The sbeⅡα gene plays a key role in controlling the synthesis of starch, in particular, the biosynthesis of amylopectin,in maturing wheat grain.To investigate its regulatory mechanisms and endosperm-specific expression pattern, the sbeⅡα promoter (3094 bp in length) was cloned using APCR and sequenced.The effect of a series of deletions was studied using a GUS transient assay system. Results showed that the 3094 bp sequence (sbe.g construct) exhibited full stable promoting activity and that the activities of 5′ or 3′ deletions reduced levels of GUS expression. Some constructs with internal deletions showed only weak activity, however,sbe.e, with a deletion from -1579—--1210 bp resulted in higher levels of expression than the full-length promoter sequence, sbe.g. This indicates that motifs such as the -300 bp element, G-box and/or P-box act as positive elements and are necessary in determining the promoter‘s endosperm-specific pattern and that negative repressor elements or motifs may also be present within the -1579—-1210 bp sequence. The age of wheate ndosperm tissue used in the GUS-transient assay system is shown to be of significant importance.     

Chromatin remodelling at a DNA double-strand break site in Saccharomyces cerevisiae

The repair of DNA double-strand breaks (DSBs) is crucial for maintaining genome stability. Eukaryotic cells repair DSBs by both non-homologous end joining and homologous recombination. How chromatin structure is altered in response to DSBs and how such alterations influence DSB repair processes are important issues. In vertebrates, phosphorylation of the histone variant H2A.X occurs rapidly after DSB formation, spreads over megabase chromatin domains, and is required for stable accumulation of repair proteins at damage foci. In Saccharomyces cerevisiae, phosphorylation of the two principal H2A species is also signalled by DSB formation, which spreads approximately 40 kb in either direction from the DSB. Here we show that near a DSB phosphorylation of H2A is followed by loss of histones H2B and H3 and increased sensitivity of chromatin to digestion by micrococcal nuclease; however, phosphorylation of H2A and nucleosome loss occur independently. The DNA damage sensor MRX is required for histone loss, which also depends on INO80, a nucleosome remodelling complex. The repair protein Rad51 (ref. 6) shows delayed recruitment to DSBs in the absence of histone loss, suggesting that MRX-dependent nucleosome remodelling regulates the accessibility of factors directly involved in DNA repair by homologous recombination. Thus, MRX may regulate two pathways of chromatin changes: nucleosome displacement for efficient recruitment of homologous recombination proteins; and phosphorylation of H2A, which modulates checkpoint responses to DNA damage.     

Atrial natriuretic peptide causes pre-glomerular vasodilatation and post-glomerular vasoconstriction in rat kidney

Atrial natriuretic peptide (ANP) can be extracted from rat hearts, and is found to increase fluid excretion by the kidneys when injected into test animals. The mechanism of ANP action is still unclear. ANP may reduce sodium reabsorption in the renal tubules, but it is also known that it increases the rate of glomerular filtration in the kidney, and relaxes preparations of smooth muscle, including one made from arteries that supply the kidney. To clarify its mode of action, we have studied directly the effects of semi-purified and synthetic ANP on blood vessels in the kidney of anaesthetized rats. We found that ANP causes a vasodilatation of the blood vessels which supply the glomeruli and a vasoconstriction of the arterioles which drain them. This substantiates the finding that increased filtration pressure participates in the natriuretic response.     

DNA sequence and analysis of human chromosome 9

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.     

Effects of alanine,glycine and glutamic acid on nitrogenous excretion byAmphiuma means liver in organ culture

Summary High concentrations (10 mM) of alanine, glycine, and glutamic acid in the culture medium had no effect on urea production inAmphiuma means liver in organ culture. Ammonia production was increased in media containing added alanine and glycine, but reduced in medium with added glutamic acid.We gratefully acknowledge the support of The Wellcome Trust.     

Newton,Gases, and Daltonian chemistry: The foundations of combination in definite proportion

This study deals with the relationship between Newton's gas model in the Principia (Book II, Proposition xxiii) and Dalton's theorizing. Dalton's first theory of mixed gases is an elegant extension of the Newtonian gas model which, in turn, led Dalton to a general model of chemical combination. The views on combination are contrasted with those of Arnold Thackray. Interestingly, the model of combination was knowingly based on a falsified theory.