The DNA helicase BRIP1 is defective in Fanconi anemia complementation group J

The protein predicted to be defective in individuals with Fanconi anemia complementation group J (FA-J), FANCJ, is a missing component in the Fanconi anemia pathway of genome maintenance. Here we identify pathogenic mutations in eight individuals with FA-J in the gene encoding the DEAH-box DNA helicase BRIP1, also called FANCJ. This finding is compelling evidence that the Fanconi anemia pathway functions through a direct physical interaction with DNA.     

Structural features of prions explored by sequence analysis¶I. Sequence data

Animal prion proteins (PrPs) form at the sequence level a very homogenous and 'closed' family. Therefore, few of their structural and functional features can be gleaned from sequence comparison as is now possible on a wide scale for other protein families. To detect putatively related proteins (at the structural and/or functional level), we used a battery of sequence analysis tools. This analysis resulted in (i) the identification of a putative 'prion-like' domain within the envelope of foamy retroviruses, (ii) the detection of putative similarities between prions and an interferon-inducible membrane protein, and (iii) the proposal that of the TATA-box-binding protein is a structural scaffold, which might allow understanding of a key event leading to the structural conversion from PrP(C) (normal cellular prion structure) towards PrP(Sc) (pathogenic structure).     

Discrete stages in the solvation and ionization of hydrogen chloride adsorbed on ice particles

Ionization and dissociation reactions play a fundamental role in aqueous chemistry. A basic and well-understood example is the reaction between hydrogen chloride (HCl) and water to form chloride ions (Cl(-)) and hydrated protons (H(3)O(+) or H(5)O(2)(+)). This acid ionization process also occurs in small water clusters and on ice surfaces, and recent attention has focused on the mechanism of this reaction in confined-water media and the extent of solvation needed for it to proceed. In fact, the transformation of HCl adsorbed on ice surfaces from a predominantly molecular form to ionic species during heating from 50 to 140 K has been observed. But the molecular details of this process remain poorly understood. Here we report infrared transmission spectroscopic signatures of distinct stages in the solvation and ionization of HCl adsorbed on ice nanoparticles kept at progressively higher temperatures. By using Monte Carlo and ab initio simulations to interpret the spectra, we are able to identify slightly stretched HCl molecules, strongly stretched molecules on the verge of ionization, contact ion pairs comprising H(3)O(+) and Cl(-), and an ionic surface phase rich in Zundel ions, H(5)O(2)(+).     

TRPV3 is a temperature-sensitive vanilloid receptor-like protein

Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin. Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception. This and other experiments--such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons--suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 degrees C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.     

General patterns of taxonomic and biomass partitioning in extant and fossil plant communities

A central goal of evolutionary ecology is to identify the general features maintaining the diversity of species assemblages. Understanding the taxonomic and ecological characteristics of ecological communities provides a means to develop and test theories about the processes that regulate species coexistence and diversity. Here, using data from woody plant communities from different biogeographic regions, continents and geologic time periods, we show that the number of higher taxa is a general power-function of species richness that is significantly different from randomized assemblages. In general, we find that local communities are characterized by fewer higher taxa than would be expected by chance. The degree of taxonomic diversity is influenced by modes of dispersal and potential biotic interactions. Further, changes in local diversity are accompanied by regular changes in the partitioning of community biomass between taxa that are also described by a power function. Our results indicate that local and regional processes have consistently regulated community diversity and biomass partitioning for millions of years.     

Structural features of prions explored by sequence analysis. II. A PrP<Superscript>Sc</Superscript> model

Prion diseases are neurodegenerative disorders associated with a conformational conversion of the prion PrP protein, in which the β-strand content increases and that of the α helix decreases. However, the structure of the pathogenous form PrP^Sc, occurring after conformational conversion of the normal cellular form PrP^C, is not yet known. From sequence analysis, we have previously proposed that helix H2 of the prion PrP^C structure might be a key region for this structural conversion. More recently, we identified the TATA box-binding protein fold as a putative scaffold that may locally satisfy the predicted secondary-structure organisation of PrP^Sc. In the present analysis, we detail the schematic construction of PrP^Sc monomeric and dimeric models, based on this hypothesis. These models are globally compatible with available data and therefore may provide further insights into the structurally and functionally elusive PrP protein. Some comments are also devoted to a comparison of the yeast Ure2p prion and animal prions. Received 29 July 2002; received after revision 24 October 2002; accepted 24 October 2002 RID="*" ID="*"Corresponding author.     

Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy

Mental retardation and epilepsy often occur together. They are both heterogeneous conditions with acquired and genetic causes. Where causes are primarily genetic, major advances have been made in unraveling their molecular basis. The human X chromosome alone is estimated to harbor more than 100 genes that, when mutated, cause mental retardation. At least eight autosomal genes involved in idiopathic epilepsy have been identified, and many more have been implicated in conditions where epilepsy is a feature. We have identified mutations in an X chromosome-linked, Aristaless-related, homeobox gene (ARX), in nine families with mental retardation (syndromic and nonspecific), various forms of epilepsy, including infantile spasms and myoclonic seizures, and dystonia. Two recurrent mutations, present in seven families, result in expansion of polyalanine tracts of the ARX protein. These probably cause protein aggregation, similar to other polyalanine and polyglutamine disorders. In addition, we have identified a missense mutation within the ARX homeodomain and a truncation mutation. Thus, it would seem that mutation of ARX is a major contributor to X-linked mental retardation and epilepsy.     

FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation

X-linked mental retardation (XLMR) is an inherited condition that causes failure to develop cognitive abilities, owing to mutations in a gene on the X chromosome. The latest XLMR update lists up to 136 conditions leading to 'syndromic', or 'specific', mental retardation (MRXS) and 66 entries leading to 'nonspecific' mental retardation (MRX). For 9 of the 66 MRX entries, the causative gene has been identified. Our recent discovery of the contiguous gene deletion syndrome ATS-MR (previously known as Alport syndrome, mental retardation, midface hypoplasia, elliptocytosis, OMIM #300194), characterized by Alport syndrome (ATS) and mental retardation (MR), indicated Xq22.3 as a region containing one mental retardation gene. Comparing the extent of deletion between individuals with ATS-MR and individuals with ATS alone allowed us to define a critical region for mental retardation of approximately 380 kb, containing four genes. Here we report the identification of two point mutations, one missense and one splice-site change, in the gene FACL4 in two families with nonspecific mental retardation. Analysis of enzymatic activity in lymphoblastoid cell lines from affected individuals of both families revealed low levels compared with normal cells, indicating that both mutations are null mutations. All carrier females with either point mutations or genomic deletions in FACL4 showed a completely skewed X-inactivation, suggesting that the gene influences survival advantage. FACL4 is the first gene shown to be involved in nonspecific mental retardation and fatty-acid metabolism.     

Plasmon-assisted transmission of entangled photons

The state of a two-particle system is said to be entangled when its quantum-mechanical wavefunction cannot be factorized into two single-particle wavefunctions. This leads to one of the strongest counter-intuitive features of quantum mechanics, namely non-locality. Experimental realization of quantum entanglement is relatively easy for photons; a starting photon can spontaneously split into a pair of entangled photons inside a nonlinear crystal. Here we investigate the effects of nanostructured metal optical elements on the properties of entangled photons. To this end, we place optically thick metal films perforated with a periodic array of subwavelength holes in the paths of the two entangled photons. Such arrays convert photons into surface-plasmon waves--optically excited compressive charge density waves--which tunnel through the holes before reradiating as photons at the far side. We address the question of whether the entanglement survives such a conversion process. Our coincidence counting measurements show that it does, so demonstrating that the surface plasmons have a true quantum nature. Focusing one of the photon beams on its array reduces the quality of the entanglement. The propagation of the surface plasmons makes the array effectively act as a 'which way' detector.