Transcription-replication conflicts: How they occur and how they are resolved

The frequent occurrence of transcription and DNA replication in cells results in many encounters, and thus conflicts, between the transcription and replication machineries. These conflicts constitute a major intrinsic source of genome instability, which is a hallmark of cancer cells. How the replication machinery progresses along a DNA molecule occupied by an RNA polymerase is an old question. Here we review recent data on the biological relevance of transcription-replication conflicts, and the factors and mechanisms that are involved in either preventing or resolving them, mainly in eukaryotes. On the basis of these data, we provide our current view of how transcription can generate obstacles to replication, including torsional stress and non-B DNA structures, and of the different cellular processes that have evolved to solve them

Role of B-cell receptors for B-cell development and antigen-induced differentiation

B-cell development is characterized by a number of tightly regulated selection processes. Signals through the B-cell receptor (BCR) guide and are required for B-cell maturation, survival, and fate decision. Here, we review the role of the BCR during B-cell development, leading to the emergence of B1, marginal zone, and peripheral follicular B cells. Furthermore, we discuss BCR-derived signals on activated B cells that lead to germinal center and plasma cell differentiation

FcγRIIb differentially regulates pre-immune and germinal center B cell tolerance in mouse and human.

Several tolerance “checkpoints” exist throughout B cell development to control autoreactive B cells and prevent the generation of pathogenic autoantibodies. FcγRIIb is an Fc receptor that inhibits B cell activation and, if defective, is associated with autoimmune disease. Its impact on specific B cell tolerance checkpoints is unknown. Here we show that reduced expression of FcγRIIb leads to increased deletion and anergy of autoreactive immature B cells, but despite this autoreactive B cells expand in the germinal center and serum autoantibodies are produced, even in response to exogenous non-self antigen. Thus, we show FcγRIIb has opposing effects on pre- and post-immune tolerance checkpoints, and suggest B cell tolerance requires the control of “bystander” germinal center B cells with low or no affinity for the immunization antigen.This work was funded by the Wellcome Trust (Programme Grant Number 083650/Z/07/Z to KGCS) and supported by the NIHR Cambridge Biomedical Research Centre. ME was funded by the Wellcome Trust (Programme Grant Number 083650/Z/07/Z), by a Junior Team Leader starting grant from the Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LabEx LERMIT) supported by a grant from ANR (ANR-10-LABX-33) under the program “Investissements d'Avenir” (ANR-11-IDEX-0003-01) and by an ANR @RAction starting grant (ANR-14-ACHN- 0008). KGCS is an NIHR Senior Clinical Investigator and a Distinguished Innovator of the Lupus Research Institute

First muon-neutrino disappearance study with an off-axis beam

We report a measurement of muon-neutrino disappearance in the T2K experiment. The 295-km muon-neutrino beam from Tokai to Kamioka is the first implementation of the off-axis technique in a long-baseline neutrino oscillation experiment

Morphological Characteristics, Genetic Diversity and Classification of Chrysanthemum Genotypes

Chrysanthemum is one of the most important ornamental plants. The genus chrysanthemum is a popular cut flower, medicinal and pot plant. Morphological traits such as cut rooting and leaf characteristics and genetic diversity among 50 genotypes of chrysanthemum morifolium were analyzed. Based on analysis of variance of data all traits in the studied genotypes showed significant differences at 1% level. The results of correlation coefficient indicated a positive and significant correlation between stem length, leaf length, leaf width and leaf serration number.The leaf length showed the highest correlation (r = +0.90**) with leaf width. Results showed that stem length and petiole length had the highest (h2>80%) heritability. Cluster analysis according to the morphological traits using the Ward method classified all the genotypes into six groups. In this classification, two genotypes (‘Takapo’ and ‘Poloneh’) were classified into one cluster that was characterized by tall stem and low branch number. In this study, canonical discriminant analysis of 20 morphological traits revealed that 3 canonical discriminant variables explained 89.6% of the total variation among genotypes. Results revealed that among the studied traits, number of cutting root, leaf size, petiol length, stem length, number of branches and number of offsets were the most important traits for discriminating among chrysanthemum genotypes. The results of this study indicate that these traits are useful for selecting and identify superior genotypes of chrysanthemum germplasm. Using some of the genotypes belonging to cluster A (with a small size of plant) and genotypes belonging to cluster E (with a large size of plant) as parents can be practiced as a criteria for breeding programs

Printable Nanophotonic Devices <i>via</i> Holographic Laser Ablation

Holography plays a significant role in applications such as data storage, light trapping, security, and biosensors. However, conventional fabrication methods remain time-consuming, costly, and complex, limiting the fabrication of holograms and their extensive use. Here, we demonstrate a single-pulse laser ablation technique to write parallel surface gratings and Fresnel zone plates. We utilized a 6 ns high-energy green laser pulse to form interference patterns to record a surface grating with 820 nm periodicity and asymmetric zone plate holograms on 4.5 nm gold-coated substrates. The holographic recording process was completed within seconds. The optical characteristics of the interference patterns have been computationally modeled, and well-ordered polychromatic diffraction was observed from the fabricated holograms. The zone plate showed a significant diffraction angle of 32° from the normal incident for the focal point. The nanosecond laser interference ablation for rapid hologram fabrication holds great potential in a vast range of optical devices