Drosophila nuclear lamin precursor Dm0 is translated from either of two developmentally regulated mRNA species apparently encoded by a single gene.

A cDNA clone encoding a portion of Drosophila nuclear lamins Dm1 and Dm2 has been identified by screening a lambda-gt11 cDNA expression library using Drosophila lamin-specific monoclonal antibodies. Two different developmentally regulated mRNA species were identified by Northern blot analysis using the initial cDNA as a probe, and full-length cDNA clones, apparently corresponding to each message, have been isolated. In vitro transcription of both full-length cDNA clones in a pT7 transcription vector followed by in vitro translation in wheat germ lysate suggests that both clones encode lamin Dm0, the polypeptide precursor of lamins Dm1 and Dm2. Nucleotide sequence analyses confirm the impression that both cDNA clones code for the identical polypeptide, which is highly homologous with human lamins A and C as well as with mammalian intermediate filament proteins. The two clones differ in their 3'-untranslated regions. In situ hybridization of lamin cDNA clones to Drosophila polytene chromosomes shows only a single locus of hybridization at or near position 25F on the left arm of chromosome 2. Southern blot analyses of genomic DNA are consistent with the notion that a single or only a few highly similar genes encoding Drosophila nuclear lamin Dm0 exist in the genome

The temperature dependence of FeRh's transport properties

The finite-temperature transport properties of FeRh compounds are investigated by first-principles Density Functional Theory-based calculations. The focus is on the behavior of the longitudinal resistivity with rising temperature, which exhibits an abrupt decrease at the metamagnetic transition point, $T = T_m$ between ferro- and antiferromagnetic phases. A detailed electronic structure investigation for $T \geq 0$ K explains this feature and demonstrates the important role of (i) the difference of the electronic structure at the Fermi level between the two magnetically ordered states and (ii) the different degree of thermally induced magnetic disorder in the vicinity of $T_m$, giving different contributions to the resistivity. To support these conclusions, we also describe the temperature dependence of the spin-orbit induced anomalous Hall resistivity and Gilbert damping parameter. For the various response quantities considered the impact of thermal lattice vibrations and spin fluctuations on their temperature dependence is investigated in detail. Comparison with corresponding experimental data finds in general a very good agreement

Generalized Bell Inequality Experiments and Computation

We consider general settings of Bell inequality experiments with many parties, where each party chooses from a finite number of measurement settings each with a finite number of outcomes. We investigate the constraints that Bell inequalities place upon the correlations possible in a local hidden variable theories using a geometrical picture of correlations. We show that local hidden variable theories can be characterized in terms of limited computational expressiveness, which allows us to characterize families of Bell inequalities. The limited computational expressiveness for many settings (each with many outcomes) generalizes previous results about the many-party situation each with a choice of two possible measurements (each with two outcomes). Using this computational picture we present generalizations of the Popescu-Rohrlich non-local box for many parties and non-binary inputs and outputs at each site. Finally, we comment on the effect of pre-processing on measurement data in our generalized setting and show that it becomes problematic outside of the binary setting, in that it allows local hidden variable theories to simulate maximally non-local correlations such as those of these generalised Popescu-Rohrlich non-local boxes.Comment: 16 pages, 2 figures, supplemental material available upon request. Typos corrected and references adde

A note on light velocity anisotropy

It is proved that in experiments on or near the Earth, no anisotropy in the one-way velocity of light may be detected. The very accurate experiments which have been performed to detect such an effect are to be considered significant tests of both special relativity and the equivalence principleComment: 8 pages, LaTex, Gen. Relat. Grav. accepte

The temperature dependence of FeRh’s transport properties

The finite-temperature transport properties of FeRh compounds are investigated by first-principles Density Functional Theory-based calculations. The focus is on the behavior of the longitudinal resistivity with rising temperature, which exhibits an abrupt decrease at the metamagnetic transition point, T = Tm between ferro- and antiferromagnetic phases. A detailed electronic structure investigation for T ≥ 0 K explains this feature and demonstrates the important role of (i) the difference of the electronic structure at the Fermi level between the two magnetically ordered states and (ii) the different degree of thermally induced magnetic disorder in the vicinity of Tm, giving different contributions to the resistivity. To support these conclusions, we also describe the temperature dependence of the spin-orbit induced anomalous Hall resistivity and Gilbert damping parameter. For the various response quantities considered the impact of thermal lattice vibrations and spin fluctuations on their temperature dependence is investigated in detail. Comparison with corresponding experimental data finds in general a very good agreement

SUN-domain proteins: 'Velcro' that links the nucleoskeleton to the cytoskeleton

The novel SUN-domain family of nuclear envelope proteins interacts with various KASH-domain partners to form SUN-domain-dependent 'bridges' across the inner and outer nuclear membranes. These bridges physically connect the nucleus to every major component of the cytoskeleton. SUN-domain proteins have diverse roles in nuclear positioning, centrosome localization, germ-cell development, telomere positioning and apoptosis. By serving both as mechanical adaptors and nuclear envelope receptors, we propose that SUN-domain proteins connect cytoplasmic and nucleoplasmic activities

Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications.

Methylation of cytosine deoxynucleotides generates 5-methylcytosine (m(5)dC), a well-established epigenetic mark. However, in higher eukaryotes much less is known about modifications affecting other deoxynucleotides. Here, we report the detection of N(6)-methyldeoxyadenosine (m(6)dA) in vertebrate DNA, specifically in Xenopus laevis but also in other species including mouse and human. Our methylome analysis reveals that m(6)dA is widely distributed across the eukaryotic genome and is present in different cell types but is commonly depleted from gene exons. Thus, direct DNA modifications might be more widespread than previously thought.M.J.K. was supported by the Long-Term Human Frontiers Fellowship (LT000149/2010-L), the Medical Research Council grant (G1001690), and by the Isaac Newton Trust Fellowship (R G76588). The work was sponsored by the Biotechnology and Biological Sciences Research Council grant BB/M022994/1 (J.B.G. and M.J.K.). The Gurdon laboratory is funded by the grant 101050/Z/13/Z (J.B.G.) from the Wellcome Trust, and is supported by the Gurdon Institute core grants, namely by the Wellcome Trust Core Grant (092096/Z/10/Z) and by the Cancer Research UK Grant (C6946/A14492). C.R.B. and G.E.A. are funded by the Wellcome Trust Core Grant. We are grateful to D. Simpson and R. Jones-Green for preparing X. laevis eggs and oocytes, F. Miller for providing us with M. musculus tissue, T. Dyl for X. laevis eggs and D. rerio samples, and to Gurdon laboratory members for their critical comments. We thank U. Ruether for providing us with M. musculus kidney DNA (Entwicklungs- und Molekularbiologie der Tiere, Heinrich Heine Universitaet Duesseldorf, Germany). We also thank J. Ahringer, S. Jackson, A. Bannister and T. Kouzarides for critical input and advice, M. Sciacovelli and E. Gaude for suggestions.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nsmb.314

Blood-Brain Barrier Breakdown in a Single Post-stroke Rodent Brain

Stroke is a major cause of global morbidity and mortality. Middle cerebral artery occlusion (MCAO) has historically been the most common animal model of simulating ischemic stroke. The extent of neurological injury after MCAO is typically measured by cerebral edema, infarct zone, and blood-brain barrier (BBB) permeability. A significant limitation of these methods is that separate sets of brains must be used for each measurement. Here we examine an alternative method of measuring cerebral edema, infarct zone and BBB permeability following MCAO in the same set of brain samples. Ninety-six rats were randomly divided into three experimental groups. Group 1 (n = 27) was used for the evaluation of infarct zone and brain edema in rats post-MCAO (n = 17) vs. sham-operated controls (n = 10). Group 2 (n = 27) was used for the evaluation of BBB breakdown in rats post-MCAO (n = 15) vs. sham-operated controls (n = 10). In Group 3 (n = 42), all three parameters were measured in the same set of brain slices in rats post-MCAO (n = 26) vs. sham-operated controls (n = 16). The effect of Evans blue on the accuracy of measuring infarct zone by 2,3,5-triphenyltetrazolium chloride (TTC) staining was determined by measuring infarct zone with and without an applied blue filter. The effects of various concentrations of TTC (0, 0.05, 0.35, 0.5, 1, and 2%) on the accuracy of measuring BBB permeability was also assessed. There was an increase in infarct volume (p < 0.01), brain edema (p < 0.01) and BBB breakdown (p < 0.01) in rats following MCAO compared to sham-operated controls, whether measured separately or together in the same set of brain samples. Evans blue had an effect on measuring infarct volume that was minimized by the application of a blue filter on scanned brain slices. There was no difference in the Evans blue extravasation index for the brain tissue samples without TTC compared to brain tissue samples incubated in TTC. Our results demonstrate that measuring cerebral edema, infarct zone and BBB permeability following MCAO can accurately be measured in the same set of brain samples

Lamin B1 regulates somatic mutations and progression of B-cell malignancies

Somatic hypermutation (SHM) is a pivotal process in adaptive immunity that occurs in the germinal centre and allows B cells to change their primary DNA sequence and diversify their antigen receptors. Here, we report that genome binding of Lamin B1, a component of the nuclear envelope involved in epigenetic chromatin regulation, is reduced during B-cell activation and formation of lymphoid germinal centres. Chromatin immunoprecipitation-Seq analysis showed that kappa and heavy variable immunoglobulin domains were released from the Lamin B1 suppressive environment when SHM was induced in B cells. RNA interference-mediated reduction of Lamin B1 resulted in spontaneous SHM as well as kappa-light chain aberrant surface expression. Finally, Lamin B1 expression level correlated with progression-free and overall survival in chronic lymphocytic leukaemia, and was strongly involved in the transformation of follicular lymphoma. In summary, here we report that Lamin B1 is a negative epigenetic regulator of SHM in normal B-cells and a 'mutational gatekeeper', suppressing the aberrant mutations that drive lymphoid malignancy