Mutations in the cyclin family member FAM58A cause an X-linked dominant disorder characterized by syndactyly, telecanthus and anogenital and renal malformations

We identified four girls with a consistent constellation of facial dysmorphism and malformations previously reported in a single mother-daughter pair. Toe syndactyly, telecanthus and anogenital and renal malformations were present in all affected individuals; thus, we propose the name 'STAR syndrome' for this disorder. Using array CGH, qPCR and sequence analysis, we found causative mutations in FAM58A on Xq28 in all affected individuals, suggesting an X-linked dominant inheritance pattern for this recognizable syndrome.     

Methylazo and methylazoxy compounds; new types of antitumour agents

Zusammenfassung Die tumorhemmende Wirkung von Methylazo- und Methylazoxyverbindungen wird beschrieben. Der cytostatische Effekt dieser Substanzen geht meistens demjenigen der analogen Methylhydrazinderivate parallel. Die Aktivität ist geringer und die therapeutischen Indices der Azo- und Azoxyverbindungen sind ungünstiger als diejenigen der entsprechenden Methylhydrazinverbindungen.     

Microbial activity in the terrestrial subsurface

Summary Little is known about the layers under the earth's crust. Only in recent years have techniques for sampling the deeper subsurface been developed to permit investigation of the subsurface environment. Prevailing conditions in the subsurface habitat such as nutrient availability, soil composition, redox potential, permeability and a variety of other factors can influence the microflora that flourish in a given environment. Microbial diversity varies between geological formations, but in general sandy soils support growth better than soils rich in clay. Bacteria predominate in subsurface sediments, while eukaryotes constitute only 1–2% of the microorganisms. Recent investigations revealed that most uncontaminated subsurface soils support the growth of aerobic heteroorganotrophic bacteria, but obviously anaerobic microorganisms also exist in the deeper subsurface habitat. The microorganisms residing below the surface of the earth are capable of degrading both natural and xenobiotic contaminants and can thereby adapt to growth under polluted conditions.     

Real-time observation of trigger factor function on translating ribosomes

The contribution of co-translational chaperone functions to protein folding is poorly understood. Ribosome-associated trigger factor (TF) is the first molecular chaperone encountered by nascent polypeptides in bacteria. Here we show, using fluorescence spectroscopy to monitor TF function and structural rearrangements in real time, that TF interacts with ribosomes and translating polypeptides in a dynamic reaction cycle. Ribosome binding stabilizes TF in an open, activated conformation. Activated TF departs from the ribosome after a mean residence time of approximately 10 s, but may remain associated with the elongating nascent chain for up to 35 s, allowing entry of a new TF molecule at the ribosome docking site. The duration of nascent-chain interaction correlates with the occurrence of hydrophobic motifs in translating polypeptides, reflecting a high aggregation propensity. These findings can explain how TF prevents misfolding events during translation and may provide a paradigm for the regulation of nucleotide-independent chaperones.     

A dark jet dominates the power output of the stellar black hole Cygnus X-1

Black holes undergoing accretion are thought to emit the bulk of their power in the X-ray band by releasing the gravitational potential energy of the infalling matter. At the same time, they are capable of producing highly collimated jets of energy and particles flowing out of the system with relativistic velocities. Here we show that the 10-solar-mass (10M(o)) black hole in the X-ray binary Cygnus X-1 (refs 3-5) is surrounded by a large-scale (approximately 5 pc in diameter) ring-like structure that appears to be inflated by the inner radio jet. We estimate that in order to sustain the observed emission of the ring, the jet of Cygnus X-1 has to carry a kinetic power that can be as high as the bolometric X-ray luminosity of the binary system. This result may imply that low-luminosity stellar-mass black holes as a whole dissipate the bulk of the liberated accretion power in the form of 'dark', radiatively inefficient relativistic outflows, rather than locally in the X-ray-emitting inflow.     

The excitation of solar-like oscillations in a δSct star by efficient envelope convection

Delta Scuti (δSct) stars are opacity-driven pulsators with masses of 1.5-2.5 M⊙, their pulsations resulting from the varying ionization of helium. In less massive stars such as the Sun, convection transports mass and energy through the outer 30 per cent of the star and excites a rich spectrum of resonant acoustic modes. Based on the solar example, with no firm theoretical basis, models predict that the convective envelope in δSct stars extends only about 1 per cent of the radius, but with sufficient energy to excite solar-like oscillations. This was not observed before the Kepler mission, so the presence of a convective envelope in the models has been questioned. Here we report the detection of solar-like oscillations in the δSct star HD187547, implying that surface convection operates efficiently in stars about twice as massive as the Sun, as the ad hoc models predicted.     

Linear ubiquitination prevents inflammation and regulates immune signalling

Members of the tumour necrosis factor (TNF) receptor superfamily have important functions in immunity and inflammation. Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were implicated in TNF signalling, yet their relevance in vivo remained uncertain. Here we identify SHARPIN as a third component of the linear ubiquitin chain assembly complex, recruited to the CD40 and TNF receptor signalling complexes together with its other constituents, HOIL-1 and HOIP. Mass spectrometry of TNF signalling complexes revealed RIP1 (also known as RIPK1) and NEMO (also known as IKKγ or IKBKG) to be linearly ubiquitinated. Mutation of the Sharpin gene (Sharpin(cpdm/cpdm)) causes chronic proliferative dermatitis (cpdm) characterized by inflammatory skin lesions and defective lymphoid organogenesis. Gene induction by TNF, CD40 ligand and interleukin-1β was attenuated in cpdm-derived cells which were rendered sensitive to TNF-induced death. Importantly, Tnf gene deficiency prevented skin lesions in cpdm mice. We conclude that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation. Our results provide evidence for the relevance of linear ubiquitination in vivo in preventing inflammation and regulating immune signalling.