Sex-specific selection drives the evolution of alternative splicing in birds

Males and females of the same species share the majority of their genomes, yet they are frequently exposed to conflicting selection pressures. Gene regulation is widely assumed to resolve these conflicting sex-specific selection pressures, and although there has been considerable focus on elucidating the role of gene expression level in sex-specific adaptation, other regulatory mechanisms have been overlooked. Alternative splicing enables different transcripts to be generated from the same gene, meaning that exons which have sex-specific beneficial effects can in theory be retained in the gene product, while exons with detrimental effects can be skipped. However, at present, little is known about how sex-specific selection acts on broad patterns of alternative splicing. Here we investigate alternative splicing across males and females of multiple bird species. We identify hundreds of genes that have sex-specific patterns of splicing, and establish that sex differences in splicing are correlated with phenotypic sex differences. Additionally, we find that alternatively spliced genes have evolved rapidly as a result of sex-specific selection, and suggest that sex differences in splicing offer another route to sex-specific adaptation when gene expression level changes are limited by functional constraints. Overall, our results shed light on how a diverse transcriptional framework can give rise to the evolution of phenotypic sexual dimorphism

Far-infrared electrodynamics of superconducting Nb: comparison of theory and experiment

Complex conductivity spectra of superconducting Nb are calculated from the first principles in the frequency region around the energy gap and compared to the experimental results. The row experimental data obtained on thin films can be precisely described by these calculations.Comment: 4 pages, 3 eps figures incl. Accepted to Solid State Commu

Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord

The existence of multipotent progenitor populations in the adult forebrain has been widely studied. To extend this knowledge to the adult spinal cord we have examined the proliferation, distribution, and phenotypic fate of dividing cells in the adult rat spinal cord. Bromodeoxyuridine (BrdU) was used to label dividing cells in 13- to 14-week-old, intact Fischer rats. Single daily injections of BrdU were administered over a 12 d period. Animals were killed either 1 d or 4 weeks after the last injection of BrdU. We observed frequent cell division throughout the adult rodent spinal cord, particularly in white matter tracts (5-7% of all nuclei). The majority of BrdU-labeled cells colocalized with markers of immature glial cells. At 4 weeks, 10% of dividing cells expressed mature astrocyte and oligodendroglial markers. These data predict that 0.75% of all astrocytes and 0.82% of all oligodendrocytes are derived from a dividing population over a 4 week period. To determine the migratory nature of dividing cells, a single BrdU injection was given to animals that were killed 1 hr after the injection. In these tissues, the distribution and incidence of BrdU labeling matched those of the 4 week post injection (pi) groups, suggesting that proliferating cells divide in situ rather than migrate from the ependymal zone. These data suggest a higher level of cellular plasticity for the intact spinal cord than has previously been observed and that glial progenitors exist in the outer circumference of the spinal cord that can give rise to both astrocytes and oligodendrocytes

Simulations of cubic-tetragonal ferroelastics

We study domain patterns in cubic-tetragonal ferroelastics by solving numerically equations of motion derived from a Landau model of the phase transition, including dissipative stresses. Our system sizes, of up to 256^3 points, are large enough to reveal many structures observed experimentally. Most patterns found at late stages in the relaxation are multiply banded; all three tetragonal variants appear, but inequivalently. Two of the variants form broad primary bands; the third intrudes into the others to form narrow secondary bands with the hosts. On colliding with walls between the primary variants, the third either terminates or forms a chevron. The multipy banded patterns, with the two domain sizes, the chevrons and the terminations, are seen in the microscopy of zirconia and other cubic-tetragonal ferroelastics. We examine also transient structures obtained much earlier in the relaxation; these show the above features and others also observed in experiment.Comment: 7 pages, 6 colour figures not embedded in text. Major revisions in conten

Solvent viscosity dependence for enzymatic reactions

A mechanism for relationship of solvent viscosity with reaction rate constant at enzyme action is suggested. It is based on fluctuations of electric field in enzyme active site produced by thermally equilibrium rocking (cranckshaft motion) of the rigid plane (in which the dipole moment $\approx 3.6 D$ lies) of a favourably located and oriented peptide group (or may be a few of them). Thus the rocking of the plane leads to fluctuations of the electric field of the dipole moment. These fluctuations can interact with the reaction coordinate because the latter in its turn has transition dipole moment due to separation of charges at movement of the reacting system along it. The rocking of the plane of the peptide group is sensitive to the microviscosity of its environment in protein interior and the latter is a function of the solvent viscosity. Thus we obtain an additional factor of interrelationship for these characteristics with the reaction rate constant. We argue that due to the properties of the cranckshaft motion the frequency spectrum of the electric field fluctuations has a sharp resonance peak at some frequency and the corresponding Fourier mode can be approximated as oscillations. We employ a known result from the theory of thermally activated escape with periodic driving to obtain the reaction rate constant and argue that it yields reliable description of the preexponent where the dependence on solvent viscosity manifests itself. The suggested mechanism is shown to grasp the main feature of this dependence known from the experiment and satisfactorily yields the upper limit of the fractional index of a power in it.Comment: 36 LaTex pages, 9 Eps figures, final versio

Quantum disorder in the two-dimensional pyrochlore Heisenberg antiferromagnet

We present the results of an exact diagonalization study of the spin-1/2 Heisenberg antiferromagnet on a two-dimensional version of the pyrochlore lattice, also known as the square lattice with crossings or the checkerboard lattice. Examining the low energy spectra for systems of up to 24 spins, we find that all clusters studied have non-degenerate ground states with total spin zero, and big energy gaps to states with higher total spin. We also find a large number of non-magnetic excitations at energies within this spin gap. Spin-spin and spin-Peierls correlation functions appear to be short-ranged, and we suggest that the ground state is a spin liquid.Comment: 7 pages, 11 figures, RevTeX minor changes made, Figure 6 correcte

Topological Orthoalgebras

We define topological orthoalgebras (TOAs) and study their properties. While every topological orthomodular lattice is a TOA, the lattice of projections of a Hilbert space is an example of a lattice-ordered TOA that is not a toplogical lattice. On the other hand, we show that every compact Boolean TOA is a topological Boolean algebra. We also show that a compact TOA in which 0 is an isolated point is atomic and of finite height. We identify and study a particularly tractable class of TOAs, which we call {\em stably ordered}: those in which the upper-set generated by an open set is open. This includes all topological OMLs, and also the projection lattices of Hilbert spaces. Finally, we obtain a topological version of the Foulis-Randall representation theory for stably ordered TOAsComment: 16 pp, LaTex. Minor changes and corrections in sections 1; more substantial corrections in section

The detection of germline and somatic BRCA1/2 genetic variants through parallel testing of patients with high-grade serous ovarian cancer: a national retrospective audit

Objective To determine the frequency of germline and somatic pathogenic BRCA1 and BRCA2 variants in patients with high-grade serous ovarian cancer tested by next-generation sequencing (NGS), with the aim of defining the best strategy to be implemented in future routine testing. Design National retrospective audit. Setting The All Wales Medical Genomics Service (AWMGS). Population Patients with high-grade serous ovarian/fallopian tube/peritoneal cancer referred by oncologists to the AWMGS between February 2015 and February 2021 for germline and/or tumour testing of the BRCA1 and BRCA2 genes by NGS. Methods Analysis of NGS data from germline and/or tumour testing. Main outcome measures Frequency of BRCA1 and BRCA2 pathogenic variants. Results The overall observed germline/somatic pathogenic variant detection rate was 11.6% in the 844 patients included in this study, with a 9.2% (73/791) germline pathogenic variant detection rate. Parallel tumour and germline testing was carried out for 169 patients and the overall pathogenic variant detection rate for this cohort was 14.8%, with 6.5% (11/169) shown to have a somatic pathogenic variant. Two BRCA1 dosage variants were found during germline screens, representing 2.0% (2/98) of patients with a pathogenic variant that would have been missed through tumour testing alone. Conclusions Parallel germline and tumour BRCA1 and BRCA2 testing maximises the detection of pathogenic variants in patients with high-grade serous ovarian cancer

Search for CP violation in D0 and D+ decays

A high statistics sample of photoproduced charm particles from the FOCUS (E831) experiment at Fermilab has been used to search for CP violation in the Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/- 0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) = +0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second error is systematic. These asymmetries are consistent with zero with smaller errors than previous measurements.Comment: 12 pages, 4 figure