Modelling for the inheritance of multiple births and fertility in endangered equids: Determining risk factors and genetic parameters in donkeys (Equus asinus).

Multiple births or twinning in equids are dangerous, undesirable situations that compromise the life of the dam and resulting offspring. However, embryo vitrification and freezing techniques take advantage of individuals whose multiple ovulations allow flushing more fertilised embryos from the oviduct to be collected, increasing the productivity and profitability of reproductive techniques. Embryo preservation is especially important in highly endangered populations such as certain donkey (Equus asinus) breeds; for which conventional reproductive techniques have previously been deemed inefficient. For instance, becoming an effective alternative to artificial insemination with frozen semen to preserve the individuals' genetic material. The objective of this study was to examine the historical foaling records of Andalusian donkeys to estimate prevalence, risk factors, phenotypic and genetic parameters for multiple births, assessing the cumulative foal number born per animal, maximum foal number per birth and multiple birth number per animal. We designed a Bayesian General Animal Mixed Model with single records considering the 'fixed' effects of birth year, birth season, birth month, sex, farm, location, and husbandry system. Age was considered and included as a linear and quadratic covariate. Gibbs sampling reported heritability estimates ranging from 0.18 ± 0.101 to 0.24 ± 0.078. Genetic and phenotypic correlations ranged from 0.496 ± 0.298 to 0.846 ± 0.152 and 0.206 ± 0.063 to 0.607 ± 0.054, respectively. Predicted breeding values obtained enable the potential selection against/for these traits, offering a new perspective for donkey breeding and conservation

Variable order Mittag-Leffler fractional operators on isolated time scales and application to the calculus of variations

We introduce new fractional operators of variable order on isolated time scales with Mittag-Leffler kernels. This allows a general formulation of a class of fractional variational problems involving variable-order difference operators. Main results give fractional integration by parts formulas and necessary optimality conditions of Euler-Lagrange type.Comment: This is a preprint of a paper whose final and definite form is with Springe

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Role of computed tomography imaging for transcatheter valvular repair/insertion

During the last decade, the development of transcatheter based therapies has provided feasible therapeutic options for patients with symptomatic severe valvular heart disease who are deemed inoperable. The promising results of many nonrandomized series and recent landmark trials have increased the number of percutaneous transcatheter valve procedures in high operative risk patients. Pre-procedural imaging of the anatomy of the aortic or mitral valve and their spatial relationships is crucial to select the most appropriate device or prosthesis and to plan the percutaneous procedure. Multidetector row computed tomography provides 3-dimensional volumetric data sets allowing unlimited plane reconstructions and plays an important role in pre-procedural screening and procedural planning. This review will describe the evolving role of multidetector row computed tomography in patient selection and strategy planning of transcatheter aortic and mitral valve procedures

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Maharam-type kernel representation for operators with a trigonometric domination

[EN] Consider a linear and continuous operator T between Banach function spaces. We prove that under certain requirements an integral inequality for T is equivalent to a factorization of T through a specific kernel operator: in other words, the operator T has what we call a Maharam-type kernel representation. In the case that the inequality provides a domination involving trigonometric functions, a special factorization through the Fourier operator is given. We apply this result to study the problem that motivates the paper: the approximation of functions in L2[0, 1] by means of trigonometric series whose Fourier coefficients are given by weighted trigonometric integrals.This research has been supported by MTM2016-77054-C2-1-P (Ministerio de Economia, Industria y Competitividad, Spain).Sánchez Pérez, EA. (2017). Maharam-type kernel representation for operators with a trigonometric domination. Aequationes Mathematicae. 91(6):1073-1091. https://doi.org/10.1007/s00010-017-0507-6S10731091916Calabuig, J.M., Delgado, O., Sánchez Pérez, E.A.: Generalized perfect spaces. Indag. Math. 19(3), 359–378 (2008)Calabuig, J.M., Delgado, O., Sánchez Pérez, E.A.: Factorizing operators on Banach function spaces through spaces of multiplication operators. J. Math. Anal. Appl. 364, 88–103 (2010)Delgado, O., Sánchez Pérez, E.A.: Strong factorizations between couples of operators on Banach function spaces. J. Convex Anal. 20(3), 599–616 (2013)Dodds, P.G., Huijsmans, C.B., de Pagter, B.: Characterizations of conditional expectation type operators. Pacific J. Math. 141(1), 55–77 (1990)Flores, J., Hernández, F.L., Tradacete, P.: Domination problems for strictly singular operators and other related classes. Positivity 15(4), 595–616 (2011). 2011Fremlin, D.H.: Tensor products of Banach lattices. Math. Ann. 211, 87–106 (1974)Hu, G.: Weighted norm inequalities for bilinear Fourier multiplier operators. Math. Ineq. Appl. 18(4), 1409–1425 (2015)Halmos, P., Sunder, V.: Bounded Integral Operators on $$L^2$$ L 2 Spaces. Springer, Berlin (1978)Kantorovitch, L., Vulich, B.: Sur la représentation des opérations linéaires. Compositio Math. 5, 119–165 (1938)Kolwicz, P., Leśnik, K., Maligranda, L.: Pointwise multipliers of Calderón- Lozanovskii spaces. Math. Nachr. 286, 876–907 (2013)Kolwicz, P., Leśnik, K., Maligranda, L.: Pointwise products of some Banach function spaces and factorization. J. Funct. Anal. 266(2), 616–659 (2014)Kuo, W.-C., Labuschagne, C.C.A., Watson, B.A.: Conditional expectations on Riesz spaces. J. Math. Anal. Appl. 303, 509–521 (2005)Lindenstrauss, J., Tzafriri, L.: Classical Banach Spaces II. Springer, Berlin (1979)Maharam, D.: The representation of abstract integrals. Trans. Am. Math. Soc. 75, 154–184 (1953)Maharam, D.: On kernel representation of linear operators. Trans. Am. Math. Soc. 79, 229–255 (1955)Maligranda, L., Persson, L.E.: Generalized duality of some Banach function spaces. Indag. Math. 51, 323–338 (1989)Neugebauer, C.J.: Weighted norm inequalities for averaging operators of monotone functions. Publ. Mat. 35, 429–447 (1991)Okada, S., Ricker, W.J., Sánchez Pérez, E.A.: Optimal Domain and Integral Extension of Operators Acting in Function Spaces. Operator Theory: Adv. Appl., vol. 180. Birkhäuser, Basel (2008)Rota, G.C.: On the representation of averaging operators. Rend. Sem. Mat. Univ. Padova. 30, 52–64 (1960)Sánchez Pérez, E.A.: Factorization theorems for multiplication operators on Banach function spaces. Integr. Equ. Oper. Theory 80(1), 117–135 (2014)Schep, A.R.: Factorization of positive multilinear maps. Ill. J. Math. 28(4), 579–591 (1984)Schep, A.R.: Products and factors of Banach function spaces. Positivity 14(2), 301–319 (2010

The celiac ganglion modulates LH-induced inhibition of androstenedione release in late pregnant rat ovaries

BACKGROUND: Although the control of ovarian production of steroid hormones is mainly of endocrine nature, there is increasing evidence that the nervous system also influences ovarian steroidogenic output. The purpose of this work was to study whether the celiac ganglion modulates, via the superior ovarian nerve, the anti-steroidogenic effect of LH in the rat ovary. Using mid- and late-pregnant rats, we set up to study: 1) the influence of the noradrenergic stimulation of the celiac ganglion on the ovarian production of the luteotropic hormone androstenedione; 2) the modulatory effect of noradrenaline at the celiac ganglion on the anti-steroidogenic effect of LH in the ovary; and 3) the involvement of catecholaminergic neurotransmitters released in the ovary upon the combination of noradrenergic stimulation of the celiac ganglion and LH treatment of the ovary. METHODS: The ex vivo celiac ganglion-superior ovarian nerve-ovary integrated system was used. This model allows studying in vitro how direct neural connections from the celiac ganglion regulate ovarian steroidogenic output. The system was incubated in buffer solution with the ganglion and the ovary located in different compartments and linked by the superior ovarian nerve. Three experiments were designed with the addition of: 1) noradrenaline in the ganglion compartment; 2) LH in the ovarian compartment; and 3) noradrenaline and LH in the ganglion and ovarian compartments, respectively. Rats of 15, 19, 20 and 21 days of pregnancy were used, and, as an end point, the concentration of the luteotropic hormone androstenedione was measured in the ovarian compartment by RIA at various times of incubation. For some of the experimental paradigms the concentration of various catecholamines (dihydroxyphenylalanine, dopamine, noradrenaline and adrenaline) was also measured in the ovarian compartment by HPLC. RESULTS: The most relevant result concerning the action of noradrenaline in the celiac ganglion was found on day 21 of pregnancy resulting in the inhibition of androstenedione release from the ovarian compartment. In addition on day 15 of pregnancy, LH placed in the ovarian compartment led to an inhibition of the release of androstenedione, and this inhibitory effect was further reinforced by the joint action of noradrenaline in the celiac ganglion and LH in the ovary. The levels of catecholamines in the ovarian compartment showed differences among the experiments; of significance, the joint treatment of noradrenaline in the celiac ganglion and LH in the ovary resulted in a remarkable increase in the ovarian levels of noradrenaline and adrenaline when compared to the effect achieved by either one of the compounds added alone. CONCLUSION: Our results demonstrate that the noradrenergic stimulation of the celiac ganglion reinforces the LH-induced inhibition of androstenedione production by the ovary of late pregnant rats, and that this effect is associated with marked changes in the release of catecholamines in the ovary

Multimode fibre:Light-sheet microscopy at the tip of a needle

We also thank the UK Engineering and Physics Sciences Research Council for funding under grant EP/J01771X/1. Finally, we would like to thank EXCELLENT TEAMS (CZ.1.07/2.3.00/30.0005) from European Social Fund and CEITEC - Central European Institute of Technology (CZ.1.05/1.1.00/02.0068) from European Regional Development Fund for support.Light-sheet fluorescence microscopy has emerged as a powerful platform for 3-D volumetric imaging in the life sciences. Here, we introduce an important step towards its use deep inside biological tissue. Our new technique, based on digital holography, enables delivery of the light-sheet through a multimode optical fibre - an optical element with extremely small footprint, yet permitting complex control of light transport processes within. We show that this approach supports some of the most advanced methods in light-sheet microscopy: by taking advantage of the cylindrical symmetry of the fibre, we facilitate the wavefront engineering methods for generation of both Bessel and structured Bessel beam plane illumination. Finally, we assess the quality of imaging on a sample of fluorescent beads fixed in agarose gel and we conclude with a proof-of-principle imaging of a biological sample, namely the regenerating operculum prongs of Spirobranchus lamarcki.Publisher PDFPeer reviewe

PDEPT: polymer-directed enzyme prodrug therapy

Polymer-directed enzyme prodrug therapy (PDEPT) is a novel two-step antitumour approach using a combination of a polymeric prodrug and polymer-enzyme conjugate to generate cytotoxic drug selectively at the tumour site. In this study the polymeric prodrug N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-Gly-Phe-Leu-Gly-doxorubicin conjugate PK1 (currently under Phase II clinical evaluation) was selected as the model prodrug, and HPMA copolymer-cathepsin B as a model for the activating enzyme conjugate. Following polymer conjugation (yield of 30–35%) HPMA copolymer-cathepsin B retained ~20–25% enzymatic activity in vitro. To investigate pharmacokinetics in vivo,125I-labelled HPMA copolymer-cathepsin B was administered intravenously (i.v.) to B16F10 tumour-bearing mice. HPMA copolymer-cathespin B exhibited a longer plasma half-life (free cathepsin B t1/2α= 2.8 h; bound cathepsin B t1/2α= 3.2 h) and a 4.2-fold increase in tumour accumulation compared to the free enzyme. When PK1 (10 mg kg−1dox-equiv.) was injected i.v. into C57 mice bearing subcutaneously (s.c.) palpable B16F10 tumours followed after 5 h by HPMA copolymer-cathepsin B there was a rapid increase in the rate of dox release within the tumour (3.6-fold increase in the AUC compared to that seen for PK1 alone). When PK1 and the PDEPT combination were used to treat established B16F10 melanoma tumour (single dose; 10 mg kg−1dox-equiv.), the antitumour activity (T/C%) seen for the combination PDEPT was 168% compared to 152% seen for PK1 alone, and 144% for free dox. Also, the PDEPT combination showed activity against a COR-L23 xenograft whereas PK1 did not. PDEPT has certain advantages compared to ADEPT and GDEPT. The relatively short plasma residence time of the polymeric prodrug allows subsequent administration of polymer-enzyme without fear of prodrug activation in the circulation and polymer-enzyme conjugates have reduced immunogenicity. This study proves the concept of PDEPT and further optimisation is warranted. © 2001 Cancer Research Campaign   http://www.bjcancer.co