Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes

Background: At later stages of folliculogenesis, the mammalian ovarian follicle contains layers of epithelial granulosa cells surrounding an antral cavity. During follicle development granulosa cells replicate, secrete hormones and support the growth of the oocyte. In cattle, the follicle needs to grow > 10 mm in diameter to allow an oocyte to ovulate, following which the granulosa cells cease dividing and differentiate into the specialised cells of the corpus luteum. To better understand the molecular basis of follicular growth and granulosa cell maturation, we undertook transcriptome profiling of granulosa cells from small ( 10 mm, n = 4) healthy bovine follicles using Affymetrix microarrays (24,128 probe sets).Results: Principal component analysis for the first two components and hierarchical clustering showed clustering into two groups, small and large, with the former being more heterogeneous. Size-frequency distributions of the coefficient of variation of the signal intensities of each probe set also revealed that small follicles were more heterogeneous than the large. IPA and GO enrichment analyses revealed that processes of axonal guidance, immune signalling and cell rearrangement were most affected in large follicles. The most important networks were associated with: (A) Notch, SLIT/ROBO and PI3K signalling, and (B) ITGB5 and extracellular matrix signalling through extracellular signal related kinases (ERKs). Upstream regulator genes which were predicted to be active in large follicles included STAT and XBP1. By comparison, developmental processes such as those stimulated by KIT, IHH and MEST were most active in small follicles. MGEA5 was identified as an upstream regulator in small follicles. It encodes an enzyme that modifies the activity of many target proteins, including those involved in energy sensing, by removal of N-acetylglucosamine from serine and threonine residues.Conclusions: Our data suggest that as follicles enlarge more genes and/or pathways are activated than are inactivated, and gene expression becomes more uniform. These findings could be interpreted that either the cells in large follicles are more uniform in their gene expression, or that follicles are more uniform or a combination of both and that additional factors, such as LH, are additionally controlling the granulosa cells. © 2014 Hatzirodos et al.; licensee BioMed Central Ltd.Nicholas Hatzirodos, Helen F Irving-Rodgers, Katja Hummitzsch, Margaret L Harland, Stephanie E Morris and Raymond J Rodger

Transcriptome profiling of granulosa cells from bovine ovarian follicles during atresia

Background: The major function of the ovary is to produce oocytes for fertilisation. Oocytes mature in follicles surrounded by nurturing granulosa cells and all are enclosed by a basal lamina. During growth, granulosa cells replicate and a large fluid-filled cavity (the antrum) develops in the centre. Only follicles that have enlarged to over 10 mm can ovulate in cows. In mammals, the number of primordial follicles far exceeds the numbers that ever ovulate and atresia or regression of follicles is a mechanism to regulate the number of oocytes ovulated and to contribute to the timing of ovulation. To better understand the molecular basis of follicular atresia, we undertook transcriptome profiling of granulosa cells from healthy (n = 10) and atretic (n = 5) bovine follicles at early antral stages (< 5 mm). Results: Principal Component Analysis (PCA) and hierarchical classification of the signal intensity plots for the arrays showed primary clustering into two groups, healthy and atretic. These analyses and size-frequency plots of coefficients of variation of signal intensities revealed that the healthy follicles were more heterogeneous. Examining the differentially-expressed genes the most significantly affected functions in atretic follicles were cell death, organ development, tissue development and embryonic development. The overall processes influenced by transcription factor gene TP53 were predicted to be activated, whereas those of MYC were inhibited on the basis of known interactions with the genes in our dataset. The top ranked canonical pathway contained signalling molecules common to various inflammatory/fibrotic pathways such as the transforming growth factor-beta and tumour necrosis factor-alpha pathways. The two most significant networks also reflect this pattern of tissue remodelling/fibrosis gene expression. These networks also contain molecules which are present in the canonical pathways of hepatic fibrosis/hepatic stellate cell activation and transforming growth factor-beta signalling and were up regulated. Conclusions: Small healthy antral follicles, which have a number of growth outcomes, exhibit greater variability in gene expression, particularly in genes associated with cell division and other growth-related functions. Atresia, on the other hand, not only involves cell death but clearly is an active process similar to wound healing.Nicholas Hatzirodos, Katja Hummitzsch, Helen F Irving-Rodgers, Margaret L Harland, Stephanie E Morris and Raymond J Rodger

The Partonic Nature of Instantons

In both Yang-Mills theories and sigma models, instantons are endowed with degrees of freedom associated to their scale size and orientation. It has long been conjectured that these degrees of freedom have a dual interpretation as the positions of partonic constituents of the instanton. These conjectures are usually framed in d=3+1 and d=1+1 dimensions respectively where the partons are supposed to be responsible for confinement and other strong coupling phenomena. We revisit this partonic interpretation of instantons in the context of d=4+1 and d=2+1 dimensions. Here the instantons are particle-like solitons and the theories are non-renormalizable. We present an explicit and calculable model in d=2+1 dimensions where the single soliton in the CP^N sigma-model can be shown to be a multi-particle state whose partons are identified with the ultra-violet degrees of freedom which render the theory well-defined at high energies. We introduce a number of methods which reveal the partons inside the soliton, including deforming the sigma model and a dual version of the Bogomolnyi equations. We conjecture that partons inside Yang-Mills instantons hold the key to understanding the ultra-violet completion of five-dimensional gauge theories.Comment: 28 pages. v3: extra references and comments. Mathematica notebooks for the figures can be downloaded from http://www.damtp.cam.ac.uk/user/dt281/parton.htm

Deformed Skyrme Crystals

The Skyrme crystal, a solution of the Skyrme model, is the lowest energy-per-charge configuration of skyrmions seen so far. Our numerical investigations show that, as the period in various space directions is changed, one obtains various other configurations, such as a double square wall, and parallel vortex-like solutions. We also show that there is a sudden "phase transition" between a Skyrme crystal and the charge 4 skyrmion with cubic symmetry as the period is gradually increased in all three space directions.Comment: 13 pages, 6 figures. To be published in JHE

Variation of receptor status in cancer of the breast.

One hundred and nineteen patients with breast cancer had 2 or more lesions removed for oestrogen (REc) or progesterone receptor (RPc) assay, either synchronously (on 38 occasions) or after an interval (on 91 occasions). In all but 7 both receptors were assayed for each lesion. The assays did not agree on the presence or absence of REc alone, RPc alone or the combination of both receptors in 11, 13 and 16% respectively of the synchronous samples, compared with 23, 30 and 43% of the asynchronous samples. The differences between the synchronous and asynchronous samples were significant for the combined receptors (P = 0.007) but not for REc (P = 0.176) or RPc alone (P = 0.077). Variation between asynchronous biopsies was greater when the earlier lesion contained RPc (18/37 disagreed) than when it did not (8/50) disagreed, P = 0.0023). This was not true for oestrogen receptor. In those remaining receptor positive there was only a weak correlation between the first and second values (Spearman rank correlation coefficient, rho = 0.39 for REc, P less than 0.02, and 0.45 for RPc, 0.05 less than P less than 0.1). Receptor levels and receptor status may change with time. Biopsy is most appropriate at the time when systemic treatment is proposed

Contact Manifolds, Contact Instantons, and Twistor Geometry

Recently, Kallen and Zabzine computed the partition function of a twisted supersymmetric Yang-Mills theory on the five-dimensional sphere using localisation techniques. Key to their construction is a five-dimensional generalisation of the instanton equation to which they refer as the contact instanton equation. Subject of this article is the twistor construction of this equation when formulated on K-contact manifolds and the discussion of its integrability properties. We also present certain extensions to higher dimensions and supersymmetric generalisations.Comment: v3: 28 pages, clarifications and references added, version to appear in JHE

A New Observational Upper Limit to the Low Redshift Ionizing Background Radiation

We report a new Fabry-Perot search for Halpha emission from the intergalactic cloud HI 1225+01 in an attempt to measure the low redshift ionizing background radiation. We set a new 2 sigma upper limit on Halpha emission of 8 mR (5 x 10^{-20} ergs cm^{-2} s^{-1} arcsec^{-2}). Conversion of this limit to limits on the strength of the ionizing background requires knowledge of the ratio of the projected to total surface area of this cloud, which is uncertain. We discuss the plausible range of this ratio, and within this range find that the strength of the ionizing backround is in the lower range of, but consistent with, previous observational and theoretical estimates.Comment: 46 pages including 9 figures (7 ps, 2 gif