Age-dependent female responses to a male ejaculate signal alter demographic opportunities for selection

A central tenet of evolutionary explanations for ageing is that the strength of selection wanes with age. However, data on age-specific expression and benefits of sexually selected traits are lacking—particularly for traits subject to sexual conflict. We addressed this by using as a model the responses of Drosophila melanogaster females of different ages to receipt of sex peptide (SP), a seminal fluid protein transferred with sperm during mating. SP can mediate sexual conflict, benefitting males while causing fitness costs in females. Virgin and mated females of all ages showed significantly reduced receptivity in response to SP. However, only young virgin females also showed increased egg laying; hence, there was a narrow demographic window of maximal responses to SP. Males gained significant ‘per mating’ fitness benefits only when mating with young females. The pattern completely reversed in matings with older females, where SP transfer was costly. The overall benefits of SP transfer (hence opportunity for selection) therefore reversed with female age. The data reveal a new example of demographic variation in the strength of selection, with convergence and conflicts of interest between males and ageing females occurring over different facets of responses to a sexually antagonistic trait

A novel approach to the design of a fully integrated clinically enhanced pharmacist independent prescribing course in the UK

Objective: The Five Year Forward View (FYFV) (NHS 2014) described new roles for pharmacists such as in urgent and emergency care. Pharmacists need advanced skills to competently manage patients with health assessment, diagnostic and clinical examination skills to fulfil these roles. UCL aimed to design a novel prescribing course with fully integrated physical assessment skills teaching that would develop pharmacists with the skills to take on these new roles. The course was designed for pharmacists by practicing pharmacists using advanced skills in these new roles. / Design: The course was uniquely developed through co-creation by a team of practicing and academic pharmacists using constructive alignment (Biggs, 2003). The course aimed to develop pharmacists with the skills to make an informed decision at each instance of prescribing. Co-creation enabled the team to understand what this meant in practice and to describe the skills pharmacists would require to achieve this, that go beyond those described by the General Pharmaceutical Council (GPhC, 2019). The course was designed utilising a blended learning approach (Garrision, 2004) with real life case studies and reflective questions to embed learning in practice. The course is currently being evaluated; the first cohort are due to complete in May 2019. Evaluation of the face to face study days was through on-line questionnaires containing open and closed questions. An end of course questionnaire and interviews with course representatives, together with a follow up questionnaire six months post completion, is planned. / Results: The course has successfully recruited to two cohorts. Initial evaluation of the face to face study days suggest that the case study approach is well-received by the students and that they are learning skills they can take into their practice. / Conclusion: Interim results suggest that using co-creation has developed a course that will develop pharmacists ready to take on new roles

Computations in the deep vs superficial layers of the cerebral cortex

A fundamental question is how the cerebral neocortex operates functionally, computationally. The cerebral neocortex with its superficial and deep layers and highly developed recurrent collateral systems that provide a basis for memory-related processing might perform somewhat different computations in the superficial and deep layers. Here we take into account the quantitative connectivity within and between laminae. Using integrate-and-fire neuronal network simulations that incorporate this connectivity, we first show that attractor networks implemented in the deep layers that are activated by the superficial layers could be partly independent in that the deep layers might have a different time course, which might because of adaptation be more transient and useful for outputs from the neocortex. In contrast the superficial layers could implement more prolonged firing, useful for slow learning and for short-term memory. Second, we show that a different type of computation could in principle be performed in the superficial and deep layers, by showing that the superficial layers could operate as a discrete attractor network useful for categorisation and feeding information forward up a cortical hierarchy, whereas the deep layers could operate as a continuous attractor network useful for providing a spatially and temporally smooth output to output systems in the brain. A key advance is that we draw attention to the functions of the recurrent collateral connections between cortical pyramidal cells, often omitted in canonical models of the neocortex, and address principles of operation of the neocortex by which the superficial and deep layers might be specialized for different types of attractor-related memory functions implemented by the recurrent collaterals. [Abstract copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

A contribution to understanding the complex nature of peisleyite

The type specimen of peisleyite has been reinvestigated by a combination of scanning electron microscopy, electron probe microanalysis (EPMA) and synchrotron powder X-ray diffraction. Morphological investigation showed that mats of peisleyite crystals, individually <3 μm across, are intergrown with wavellite veinlets to form the white cryptocrystalline material that is typical of 'peisleyite'. New EPMA data (mean of 12 analyses) gave the empirical formula of peisleyite as (Na_(1.69)Ca_(0.18))_(Σ1.87)(Al_(9.04)Fe_(0.03))_(Σ9.07)[(P_(6.28)S_(1.38)Si_(0.25))O_4]_(Σ7.91)(OH)_(6.66)·27.73H_2O, or ideally Na_2Al_9[(P,S)O_4]_8(OH)_6·28H_2O. The associated wavellite was found to be F-rich. Synchrotron powder data were indexed and refined and gave the following unit cell: P1, a = 9.280(19), b = 11.976(19), c = 13.250(18) Å, α = 91.3(1), β = 75.6(1), γ = 67.67(1)º, V = 1308(5) Å3 and Z = 4. These data are significantly different to those reported in the original description of peisleyite

Atomic spectral-product representations of molecular electronic structure: metric matrices and atomic-product composition of molecular eigenfunctions

Recent progress is reported in development of ab initio computational methods for the electronic structures of molecules employing the many-electron eigenstates of constituent atoms in spectral-product forms. The approach provides a universal atomic-product description of the electronic structure of matter as an alternative to more commonly employed valence-bond- or molecular-orbital-based representations. The Hamiltonian matrix in this representation is seen to comprise a sum over atomic energies and a pairwise sum over Coulombic interaction terms that depend only on the separations of the individual atomic pairs. Overall electron antisymmetry can be enforced by unitary transformation when appropriate, rather than as a possibly encumbering or unnecessary global constraint. The matrix representative of the antisymmetrizer in the spectral-product basis, which is equivalent to the metric matrix of the corresponding explicitly antisymmetric basis, provides the required transformation to antisymmetric or linearly independent states after Hamiltonian evaluation. Particular attention is focused in the present report on properties of the metric matrix and on the atomic-product compositions of molecular eigenstates as described in the spectral-product representations. Illustrative calculations are reported for simple but prototypically important diatomic (H_2, CH) and triatomic (H_3, CH_2) molecules employing algorithms and computer codes devised recently for this purpose. This particular implementation of the approach combines Slater-orbital-based one- and two-electron integral evaluations, valence-bond constructions of standard tableau functions and matrices, and transformations to atomic eigenstate-product representations. The calculated metric matrices and corresponding potential energy surfaces obtained in this way elucidate a number of aspects of the spectral-product development, including the nature of closure in the representation, the general redundancy or linear dependence of its explicitly antisymmetrized form, the convergence of the apparently disparate atomic-product and explicitly antisymmetrized atomic-product forms to a common invariant subspace, and the nature of a chemical bonding descriptor provided by the atomic-product compositions of molecular eigenstates. Concluding remarks indicate additional studies in progress and the prognosis for performing atomic spectral-product calculations more generally and efficiently

Magnon Mediated Electric Current Drag Across a Ferromagnetic Insulator Layer

In a semiconductor hererostructure, the Coulomb interaction is responsible for the electric current drag between two 2D electron gases across an electron impenetrable insulator. For two metallic layers separated by a ferromagnetic insulator (FI) layer, the electric current drag can be mediated by a nonequilibrium magnon current of the FI. We determine the drag current by using the semiclassical Boltzmann approach with proper boundary conditions of electrons and magnons at the metal-FI interface.Comment: 13 pages, 2 figures: to appear in PR

Tracking TCRß sequence clonotype expansions during antiviral therapy using high-throughput sequencing of the hypervariable region

To maintain a persistent infection viruses such as hepatitis C virus (HCV) employ a range of mechanisms that subvert protective T cell responses. The suppression of antigen-specific T cell responses by HCV hinders efforts to profile T cell responses during chronic infection and antiviral therapy. Conventional methods of detecting antigen-specific T cells utilize either antigen stimulation (e.g., ELISpot, proliferation assays, cytokine production) or antigen-loaded tetramer staining. This limits the ability to profile T cell responses during chronic infection due to suppressed effector function and the requirement for prior knowledge of antigenic viral peptide sequences. Recently, high-throughput sequencing (HTS) technologies have been developed for the analysis of T cell repertoires. In the present study, we have assessed the feasibility of HTS of the TCRβ complementarity determining region (CDR)3 to track T cell expansions in an antigen-independent manner. Using sequential blood samples from HCV-infected individuals undergoing antiviral therapy, we were able to measure the population frequencies of &gt;35,000 TCRβ sequence clonotypes in each individual over the course of 12 weeks. TRBV/TRBJ gene segment usage varied markedly between individuals but remained relatively constant within individuals across the course of therapy. Despite this stable TRBV/TRBJ gene segment usage, a number of TCRβ sequence clonotypes showed dramatic changes in read frequency. These changes could not be linked to therapy outcomes in the present study; however, the TCRβ CDR3 sequences with the largest fold changes did include sequences with identical TRBV/TRBJ gene segment usage and high junction region homology to previously published CDR3 sequences from HCV-specific T cells targeting the HLA-B*0801-restricted 1395HSKKKCDEL1403 and HLA-A*0101-restricted 1435ATDALMTGY1443 epitopes. The pipeline developed in this proof of concept study provides a platform for the design of future experiments to accurately address the question of whether T cell responses contribute to SVR upon antiviral therapy. This pipeline represents a novel technique to analyze T cell dynamics in situations where conventional antigen-dependent methods are limited due to suppression of T cell functions and highly diverse antigenic sequences