Specificity in V(D)J recombination: new lessons from biochemistry and genetics

Recent in vitro work on V(D)J recombination has helped to clarify its mechanism. The first stage of the reaction, which can be reproduced with the purified RAG1 and RAG2 proteins, is a site-specific cleavage that generates the same broken DNA species found in vivo. The cleavage reaction is closely related to known types of transpositional recombination, such as that of HIV integrase. All the site specificity of V(D)J recombination, including the 12/23 rule, is determined by the RAG proteins. The later steps largely overlap with the repair of radiation-induced DNA double-strand breaks, as indicated by the identity of several newly characterized factors involved in repair. These developments open the way for a thorough biochemical study of V(D)J recombination

The cholesterol-raising diterpenes from coffee beans increase serum lipid transfer protein activity levels in humans

Cafestol and kahweol–diterpenes present in unfiltered coffee— strongly raise serum VLDL and LDL cholesterol and slightly reduce HDL cholesterol in humans. The mechanism of action is unknown. We determined whether the coffee diterpenes may affect lipoprotein metabolism via effects on lipid transfer proteins and lecithin:cholesterol acyltransferase in a randomized, double-blind cross-over study with 10 healthy male volunteers. Either cafestol (61–64 mg/day) or a mixture of cafestol (60 mg/day) and kahweol (48–54 mg/day) was given for 28 days. Serum activity levels of cholesterylester transfer protein, phospholipid transfer protein and lecithin:cholesterol acyltransferase were measured using exogenous substrate assays. Relative to baseline values, cafestol raised the mean (±S.D.) activity of cholesterylester transfer protein by 18±12% and of phospholipid transfer protein by 21±14% (both P<0.001). Relative to cafestol alone, kahweol had no significant additional effects. Lecithin:cholesterol acyltransferase activity was reduced by 11±12% by cafestol plus kahweol (P=0.02). It is concluded that the effects of coffee diterpenes on plasma lipoproteins may be connected with changes in serum activity levels of lipid transfer proteins

Dilatant normal faulting in jointed cohesive rocks: a physical model study

Dilatant faults often form in rocks containing pre-existing joints, but the effects of joints on fault segment linkage and fracture connectivity are not well understood. We present an analogue modeling study using cohesive powder with pre-formed joint sets in the upper layer, varying the angle between joints and a rigid basement fault. We analyze interpreted map-view photographs at maximum displacement for damage zone width, number of connected joints, number of secondary fractures, degree of segmentation and area fraction of massively dilatant fractures. Particle imaging velocimetry provides insight into the deformation history of the experiments and illustrates the localization pattern of fault segments. Results show that with increasing angle between joint-set and basement-fault strike the number of secondary fractures and the number of connected joints increase, while the area fraction of massively dilatant fractures shows only a minor increase. Models without pre-existing joints show far lower area fractions of massively dilatant fractures while forming distinctly more secondary fractures

Evolution of a highly dilatant fault zone in the grabens of Canyonlands National Park, Utah, USA - Integrating fieldwork, ground-penetrating radar and airborne imagery analysis

Abstract. The grabens of Canyonlands National Park are a young and active system of sub-parallel, arcuate grabens, whose evolution is the result of salt movement in the subsurface and a slight regional tilt of the faulted strata. We present results of ground-penetrating radar (GPR) surveys in combination with field observations and analysis of high-resolution airborne imagery. GPR data show intense faulting of the Quaternary sediments at the flat graben floors, implying a more complex fault structure than visible at the surface. Direct measurements of heave and throw at several locations to infer fault dips at depth, combined with observations of primary joint surfaces in the upper 100 m, suggest a highly dilatant fault geometry. Sinkholes observed in the field as well as in airborne imagery give insights in local dilatancy and show where water and sediments are transported underground. Based on correlations of paleosols observed in outcrops and GPR profiles, we argue that either the grabens in Canyonlands National Park are older than previously assumed or that sedimentation rates were much higher in the Pleistocene. This is the final version of the article. It first appeared from Copernicus Publications via http://dx.doi.org/10.5194/se-6-839-2015 The supplement related to this article is available online at http://dx.doi.org/10.5194/se-6-839-2015-supplemen

Complete Genome Sequences of 11 Bordetella pertussis Strains Representing the Pandemic ptxP3 Lineage

Item does not contain fulltextPathogen adaptation has contributed to the resurgence of pertussis. To facilitate our understanding of this adaptation we report here 11 completely closed and annotated Bordetella pertussis genomes representing the pandemic ptxP3 lineage. Our analyses included six strains which do not produce the vaccine components pertactin and/or filamentous hemagglutinin