ruvA Mutants that resolve Holliday junctions but do not reverse replication forks

RuvAB and RuvABC complexes catalyze branch migration and resolution of Holliday junctions (HJs) respectively. In addition to their action in the last steps of homologous recombination, they process HJs made by replication fork reversal, a reaction which occurs at inactivated replication forks by the annealing of blocked leading and lagging strand ends. RuvAB was recently proposed to bind replication forks and directly catalyze their conversion into HJs. We report here the isolation and characterization of two separation-of-function ruvA mutants that resolve HJs, based on their capacity to promote conjugational recombination and recombinational repair of UV and mitomycin C lesions, but have lost the capacity to reverse forks. In vivo and in vitro evidence indicate that the ruvA mutations affect DNA binding and the stimulation of RuvB helicase activity. This work shows that RuvA's actions at forks and at HJs can be genetically separated, and that RuvA mutants compromised for fork reversal remain fully capable of homologous recombination

Crosstalk prediction on wire bundles by Kriging approach

A wide variety of interconnections among electronic devices are performed by means of randomly twisted bundle of wires, particularly for transport and industrial applications. This work examines the crosstalk analysis of such bundles. A new model based on fractals for describing the position of wires winding throughout a bundle is presented. It allows the wires' meandering degree to be tuned simply by means of a parameter (the fractal dimension). It also allows for a statistical analysis of crosstalk because it can simulate independent different realizations of the same interconnection. An efficient multifactor prediction method known as “Kriging” is applied in order to describe the crosstalk as a function of the input factors (cable loads, cable height above the ground plane, etc.) of the cable model. It allows for a drastic reduction in the simulation time insofar as it predicts the crosstalk at untried combinations of the input factors from a small base of input combinations. In comparing the crosstalk simulated using the fractal model with the experimental measurements good agreement was foun

Reconstitution de gestes funéraires

Lors de fouilles archéologiques de sépultures, il est rare de retrouver les restes d’un linceul, surtout sous un climat tempéré. En revanche, le climat très sec de Nubie explique la conservation exceptionnelle de la matière organique (peau, cheveux, muscle, fécès…) sur l’ensemble des nécropoles de l’île de Saï. Dans une tombe probablement de l’époque chrétienne (postérieure à la culture ballanéenne – appelée aussi Groupe X – et antérieure à la conquête ottomane) de la grande nécropole nord (SN), la fouille a mis au jour un jeune sujet entièrement enveloppé d’un linceul. Cela nous a permis de reconstituer une partie des gestes qui ont accompagné l’inhumation de cet enfant. À la suite de cette étude, nous pouvons avancer l’hypothèse que le linceul a été conçu pour faciliter une position spécifique du corps lors de son dépôt dans la tombe. Il avait donc une grande importance en ce qui concerne la position finale du cadavre.In a temperate environment, during the excavation of burials, it is very rare to find the remains of shroud pieces. At the opposite, the very dry climate of the Middle Nubia can explain by itself the exceptional conservation of soft parts of the human body (hair, nails, brain, muscular fibres, human coprolithes) as it is frequently found at the North necropolis (SN) of the Saï island (Northern Province, Sudan). In a post X-group and ante-Muslim burial (T. 176), the excavation has allowed the discovery of a very young individual still wrapped in a shroud. It has been possible to reconstruct the shape of the shroud, the way in which it was wrapped and fixed around the body. This has allowed us to present the hypothesis that the shape of the shroud and the way to attach it have had a voluntary influence in the final position of the child in the pit, i. e. a dorsal decubitus of the body with the head hyper-flexed on the top of the trunk. Then, even if one side of the tissue of the shroud has been tear without care, its final shape is voluntary and implies a well defined funeral practice for such a child. In a Nubian archaeological context, such a practice is described for the first time —for the post X Group period in Sudan— at the Saï Island. Moreover, the limited extension of the excavated archaeological surface of this necropolis has allowed the discovery of other individuals (adults, juveniles) with important and also well preserved pieces of tissues or shrouds. Then, the taphonomical as well as the paleobiological potentialities of this necropolis seem to be very important

Student politics, teaching politics, black politics: an interview with Ansel Wong

Ansel Wong is the quiet man of British black politics, rarely in the limelight and never seeking political office. And yet his ‘career’ here – from Black Power firebrand to managing a multimillion budget as head of the Greater London Council’s Ethnic Minority Unit in the 1980s – spells out some of the most important developments in black educational and cultural projects. In this interview, he discusses his identification with Pan-Africanism, his involvement in student politics, his role in the establishment of youth projects and supplementary schools in the late 1960s and 1970s, and his involvement in black radical politics in London in the same period, all of which took place against the background of revolutionary ferment in the Third World and the world of ideas, and were not without their own internal class and ethnic conflicts

Steinert's syndrome presenting as anal incontinence: a case report

<p>Abstract</p> <p>Introduction</p> <p>Myotonic dystrophy (MD) or Steinert's syndrome is a rare cause of chronic diarrhea and anal incontinence. In the presence of chronic diarrhea and fecal incontinence with muscle weakness, neuromuscular disorders such as myotonic dystrophy should be considered in the differential diagnosis.</p> <p>Case Presentation</p> <p>We present the case of a 45-year-old Turkish man with Steinert's syndrome, who was not diagnosed until the age of 45.</p> <p>Conclusions</p> <p>In clinical practice, the persistence of diarrhea and fecal incontinence with muscle weakness should suggest that the physician perform an anal manometric study and electromyography. Neuromuscular disorders such as myotonic dystrophy should be considered in the differential diagnosis.</p

Prediction of tissue-specific cis-regulatory modules using Bayesian networks and regression trees

<p>Abstract</p> <p>Background</p> <p>In vertebrates, a large part of gene transcriptional regulation is operated by cis-regulatory modules. These modules are believed to be regulating much of the tissue-specificity of gene expression.</p> <p>Results</p> <p>We develop a Bayesian network approach for identifying cis-regulatory modules likely to regulate tissue-specific expression. The network integrates predicted transcription factor binding site information, transcription factor expression data, and target gene expression data. At its core is a regression tree modeling the effect of combinations of transcription factors bound to a module. A new unsupervised EM-like algorithm is developed to learn the parameters of the network, including the regression tree structure.</p> <p>Conclusion</p> <p>Our approach is shown to accurately identify known human liver and erythroid-specific modules. When applied to the prediction of tissue-specific modules in 10 different tissues, the network predicts a number of important transcription factor combinations whose concerted binding is associated to specific expression.</p

Editing of misaligned 3′-termini by an intrinsic 3′–5′ exonuclease activity residing in the PHP domain of a family X DNA polymerase

Bacillus subtilis gene yshC encodes a family X DNA polymerase (PolXBs), whose biochemical features suggest that it plays a role during DNA repair processes. Here, we show that, in addition to the polymerization activity, PolXBs possesses an intrinsic 3′–5′ exonuclease activity specialized in resecting unannealed 3′-termini in a gapped DNA substrate. Biochemical analysis of a PolXBs deletion mutant lacking the C-terminal polymerase histidinol phosphatase (PHP) domain, present in most of the bacterial/archaeal PolXs, as well as of this separately expressed protein region, allow us to state that the 3′–5′ exonuclease activity of PolXBs resides in its PHP domain. Furthermore, site-directed mutagenesis of PolXBs His339 and His341 residues, evolutionary conserved in the PHP superfamily members, demonstrated that the predicted metal binding site is directly involved in catalysis of the exonucleolytic reaction. The implications of the unannealed 3′-termini resection by the 3′–5′ exonuclease activity of PolXBs in the DNA repair context are discussed

Irradiation-Induced Deinococcus radiodurans Genome Fragmentation Triggers Transposition of a Single Resident Insertion Sequence

Stress-induced transposition is an attractive notion since it is potentially important in creating diversity to facilitate adaptation of the host to severe environmental conditions. One common major stress is radiation-induced DNA damage. Deinococcus radiodurans has an exceptional ability to withstand the lethal effects of DNA–damaging agents (ionizing radiation, UV light, and desiccation). High radiation levels result in genome fragmentation and reassembly in a process which generates significant amounts of single-stranded DNA. This capacity of D. radiodurans to withstand irradiation raises important questions concerning its response to radiation-induced mutagenic lesions. A recent study analyzed the mutational profile in the thyA gene following irradiation. The majority of thyA mutants resulted from transposition of one particular Insertion Sequence (IS), ISDra2, of the many different ISs in the D. radiodurans genome. ISDra2 is a member of a newly recognised class of ISs, the IS200/IS605 family of insertion sequences

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings