Novel pharmacological actions of Trequinsin Hydrochloride improve human sperm cell motility and function

Background and purposeAsthenozoospermia is a leading cause of male infertility, but the development of pharmaceuticals to improve sperm motility has been hindered by the lack of effective screening platforms and knowledge of suitable molecular targets. We have demonstrated that a high throughput screening (HTS) strategy in conjunction with established in vitro tests can identify and characterise the action of compounds that improve sperm motility. The study aimed to apply HTS to identify new compounds from a novel small molecule library that increase intracellular calcium, [Ca2+]I, promote human sperm cell motility and systemically determine the mechanism of action. Experimental approach A validated HTS fluorometric [Ca2+]i assay was used to screen an in-house library of compounds. Trequinsin hydrochloride (a phosphodiesterase 3 inhibitor) was selected for detailed molecular (plate reader assays, electrophysiology and cyclic nucleotide measurement) and functional (motility and acrosome reaction) testing in sperm from healthy volunteer donors and, where possible, patients.   Key resultsThe fluorometric analysis identified Trequinsin as an efficacious agonist of [Ca2+]i, although less potent than progesterone (P4). Functionally, Trequinsin significantly increased cell hyperactivation and penetration into viscous medium in all donor sperm samples and cell hyperactivation in 22/25 (88%) patient sperm samples. The Trequinsin-induced [Ca2+]i response was cross-desensitised consistently by prostaglandin E1 but not with P4. Whole-cell patch clamp electrophysiology confirmed that Trequinsin activates CatSper and partially inhibits potassium channel activity. Trequinsin also increases intracellular cGMP.   Conclusion and Implications Trequinsin exhibits a novel pharmacological profile in human sperm and may be a suitable lead compound for the development of new pharmaceuticals to improve patient sperm function and fertilisation potential

Calculation of the emission power distribution of microstructured OLEDs using the reciprocity theorem

S. Zhang, E.R. Martins, G.A. Turnbull and I.D.W. Samuel are grateful to the Scottish Universities Physics Alliance (SUPA) and the Engineering and Physical Sciences Research Council (EPSRC) for financial support.Integrating photonic microstructures into organic light-emitting diodes (OLEDs) has been a widely used strategy to improve their light out-coupling efficiency. However, there is still a need for optical modelling methods which quantitatively characterise the spatial emission pattern of microstructured OLEDs. In this paper, we demonstrate such rigorous calculation using the reciprocity theorem. The calculation of the emission intensity at each direction in the far field can be simplified into only two simple calculations of an incident plane wave propagating from the far field into a single cell of the periodic structure. The emission from microstructured OLED devices with three different grating periods was calculated as a test of the approach, and the calculated results were in good agreement with experiment. This optical modelling method is a useful calculation tool to investigate and control the spatial emission pattern of microstructured OLEDs.PostprintPeer reviewe

Quasiparticles and c-axis coherent hopping in high T_c superconductors

We study the problem of the low-energy quasiparticle spectrum of the extended t-J model and analyze the coherent hopping between weakly coupled planes described by this model. Starting with a two-band model describing the Cu-O planes and the unoccupied bands associated to the metallic atoms located in between the planes, we obtain effective hopping matrix elements describing the c-axis charge transfer. A computational study of these processes shows an anomalously large charge anisotropy for doping concentrations around and below the optimal doping.Comment: 4 pages, 3 figure

Desenvolvimento comparado de três cultivares de caupi, Vigna unguiculata (L.) Walp

An experiment was carried out to establish the comparative growth of three Vigna unguiculata cultivars throught determination of leaf area, dry matter partition and growth analysis. Leaf area established throught the method of relationship between total dry matter of leaves and dry matter of discs with knowed area, and estimated by the product of length x maximum width of leaf x 1.75did not present differences. Cultivar Epace-1 showed higher leaf area duration in relation to Epace-6 and Epace-8 cowpea cultivars. Vigna unguiculata presented an initial exponential phase of dry matter accumulation and a sygmoid phase post-maturity. Accumulation of biomass in the reproductive part of cowpea 'Epace-1' was later and more effective in relation to Epace-6 and Epace-8 cultivars. Cultivar Epace-1 presented later development in relation to 'Epace.6' and 'Epace-8'. Epace-6 cultivar of cowpea showed higher growth on the second part of the plant life cycle in relation to Epace-8 and Epace-1 cultivars. Vigna unguiculata plants presented higher net assimilation rate and relative growth rate from 30 to 50 days after emergence. Cowpea snowed higher leaf area ratio and leaf weight ratio from 28 to 42 days after emergence.Realizou-se determinação comparada da área foliar, da partição de biomassa e da análise de crescimento em três cultivares de Vigna unguiculata (Epace-1, Epace-6 e Epace-8) mantidos em vasos sob condições naturais. Ométodo de estabelecimento da área foliar baseado na correlação entre o peso da matéria seca foliar com o peso de discos foliares de área conhecida mostrou-se equivalente a estimativa (c.1) 1,75, referente aos folíolos terminais. O cultivar Epace-1 apresentou maior número de folhas, maiores incrementos na área foliar e maior duração de área foliar em relação aos cultivares Epace-6 e Epace-8. Vigna unguiculata mostrou uma fase exponencial inicial no acúmulo de matéria seca e uma tendência sigmoidal após a maturidade. O acúmulo de biomassa na parte reprodutiva do caupi iniciou-se mais tardiamente no cultivar Epace-1, sendo que este cultivar alocou maior proporção de carboidratos no sistema radicular com relação aos cultivares Epace-6 e Epace-8. Verificou-se que o cultivar Epace-1 apresentou-se mais tardio do que os cultivares Epace-6 e Epace-8. O cultivar Epace-6 apresentou um incremento no crescimento na segunda fase do ciclo de desenvolvimento com relação aos cultivares Epace-8 e Epace-1. As plantas de caupi atingiram os valores mais altos de taxa assimilatória líquida e de taxa de crescimento relativo de 30 a 50 dias após a emergência. Vigna unguiculata apresentou incrementos na razão de área foliar e na razão de peso foliar de 28 a 42 dias após a emergência

Constraints on the CMB temperature redshift dependence from SZ and distance measurements

The relation between redshift and the CMB temperature, $T_{CMB}(z)=T_0(1+z)$ is a key prediction of standard cosmology, but is violated in many non-standard models. Constraining possible deviations to this law is an effective way to test the $\Lambda$CDM paradigm and search for hints of new physics. We present state-of-the-art constraints, using both direct and indirect measurements. In particular, we point out that in models where photons can be created or destroyed, not only does the temperature-redshift relation change, but so does the distance duality relation, and these departures from the standard behaviour are related, providing us with an opportunity to improve constraints. We show that current datasets limit possible deviations of the form $T_{CMB}(z)=T_0(1+z)^{1-\beta}$ to be $\beta=0.004\pm0.016$ up to a redshift $z\sim 3$. We also discuss how, with the next generation of space and ground-based experiments, these constraints can be improved by more than one order of magnitude.Comment: 27 pages, 11 figure

Evolution of electronic and ionic structure of Mg-clusters with the growth cluster size

The optimized structure and electronic properties of neutral and singly charged magnesium clusters have been investigated using ab initio theoretical methods based on density-functional theory and systematic post-Hartree-Fock many-body perturbation theory accounting for all electrons in the system. We have systematically calculated the optimized geometries of neutral and singly charged magnesium clusters consisting of up to 21 atoms, electronic shell closures, binding energies per atom, ionization potentials and the gap between the highest occupied and the lowest unoccupied molecular orbitals. We have investigated the transition to the hcp structure and metallic evolution of the magnesium clusters, as well as the stability of linear chains and rings of magnesium atoms. The results obtained are compared with the available experimental data and the results of other theoretical works.Comment: 30 pages, 10 figures, 3 table

Percolation on two- and three-dimensional lattices

In this work we apply a highly efficient Monte Carlo algorithm recently proposed by Newman and Ziff to treat percolation problems. The site and bond percolation are studied on a number of lattices in two and three dimensions. Quite good results for the wrapping probabilities, correlation length critical exponent and critical concentration are obtained for the square, simple cubic, HCP and hexagonal lattices by using relatively small systems. We also confirm the universal aspect of the wrapping probabilities regarding site and bond dilution.Comment: 15 pages, 6 figures, 3 table