The X-linked chronic granulomatous disease gene codes for the beta-chain of cytochrome b-245

Chronic granulomatous disease (CGD) is a rare inherited disorder associated with a profound predisposition to infection due to the lack of a microbicidal oxidase system in the phagocytes of these patients. This syndrome is most commonly inherited through a defect on the X chromosome and the only clearly defined component of the oxidase system, the very unusual cytochrome b (b-245), has been shown to be missing from the cells of these patients. This cytochrome is a heterodimer composed of an alpha-chain of relative molecular mass (Mr) 23,000 (23K) and a 76-92K beta-chain; neither are detectable in neutrophils from X-linked CGD subjects. The defective X-CGD gene has recently been cloned by 'reverse genetics' but the protein predicted from the proposed complementary DNA sequence was not identified. We have purified the beta-chain of the cytochrome and sequenced 43 amino acids from the N terminus. Almost complete homology was obtained between this sequence and that of the complementary nucleotides 19-147 of the sequence of the X-CGD gene, originally designated as a non-coding region.     

Comment on “Low-frequency sea level variation and its correlation with climate events in the Pacific”

The tide gauge results exhibit strong multi-decadal oscillations with detected periodicities up to a quasi-60 years. This translates in the requirement of at least 60-70 years of continuously recorded data without any quality issue and the use of a procedure appropriate for time series with periodic components to infer the acceleration trend. This is not what is done in many recent papers where the oscillating behaviour is neglected and short or incomplete records arbitrarily extended or reconstructed are used to infer wrong accelerating trends. All the tide gauges of enough length and quality show the sea levels are oscillating with important multi-decadal periodicities but absolutely not positively accelerating. The satellite radar altimeter reconstruction of the global mean sea level only available since 1993 shows despite the many uncertainties of a still imperfect procedure a not positively accelerating behaviour. The presence of acceleration in the reconstructed or extended data sets and the lack of acceleration in all the individual tide gauge measurements of enough quality and length certainly deserve further discussion. This is a comment to a previously published original paper made on the basis of other previously published results and not a new original paper.     

Thiamine disulfide anhydride: A new fluorescent derivative of thiamine

Zusammenfassung Es wird die Isolierung eines neuen fluoreszierenden Thiaminderivates beschrieben.     

Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas

To identify somatic mutations in pediatric diffuse intrinsic pontine glioma (DIPG), we performed whole-genome sequencing of DNA from seven DIPGs and matched germline tissue and targeted sequencing of an additional 43 DIPGs and 36 non-brainstem pediatric glioblastomas (non-BS-PGs). We found that 78% of DIPGs and 22% of non-BS-PGs contained a mutation in H3F3A, encoding histone H3.3, or in the related HIST1H3B, encoding histone H3.1, that caused a p.Lys27Met amino acid substitution in each protein. An additional 14% of non-BS-PGs had somatic mutations in H3F3A causing a p.Gly34Arg alteration.     

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.     

Calcium transients in a crustacean motoneuron soma: Detection with arsenazo III

Summary Long lasting action potentials can be triggered in crayfish giant motor neurons by a short depolarizing pulse under different conditions. The concomitant increase in absorbance of the Ca indicator arsenazo III preloaded into the soma, confirms observations suggesting that these potential changes are related to a Ca inward current through the some membrane.     

Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex

RNA interference and related RNA silencing phenomena use short antisense guide RNA molecules to repress the expression of target genes. Argonaute proteins, containing amino-terminal PAZ (for PIWI/Argonaute/Zwille) domains and carboxy-terminal PIWI domains, are core components of these mechanisms. Here we show the crystal structure of a Piwi protein from Archaeoglobus fulgidus (AfPiwi) in complex with a small interfering RNA (siRNA)-like duplex, which mimics the 5' end of a guide RNA strand bound to an overhanging target messenger RNA. The structure contains a highly conserved metal-binding site that anchors the 5' nucleotide of the guide RNA. The first base pair of the duplex is unwound, separating the 5' nucleotide of the guide from the complementary nucleotide on the target strand, which exits with the 3' overhang through a short channel. The remaining base-paired nucleotides assume an A-form helix, accommodated within a channel in the PIWI domain, which can be extended to place the scissile phosphate of the target strand adjacent to the putative slicer catalytic site. This study provides insights into mechanisms of target mRNA recognition and cleavage by an Argonaute-siRNA guide complex.     

A soft solid surface on Titan as revealed by the Huygens Surface Science Package

The surface of Saturn's largest satellite--Titan--is largely obscured by an optically thick atmospheric haze, and so its nature has been the subject of considerable speculation and discussion. The Huygens probe entered Titan's atmosphere on 14 January 2005 and descended to the surface using a parachute system. Here we report measurements made just above and on the surface of Titan by the Huygens Surface Science Package. Acoustic sounding over the last 90 m above the surface reveals a relatively smooth, but not completely flat, surface surrounding the landing site. Penetrometry and accelerometry measurements during the probe impact event reveal that the surface was neither hard (like solid ice) nor very compressible (like a blanket of fluffy aerosol); rather, the Huygens probe landed on a relatively soft solid surface whose properties are analogous to wet clay, lightly packed snow and wet or dry sand. The probe settled gradually by a few millimetres after landing.