Paracrine effects of oocyte secreted factors and stem cell factor on porcine granulosa and theca cells in vitro

Oocyte control of granulosa and theca cell function may be mediated by several growth factors via a local feedback loop(s) between these cell types. This study examined both the role of oocyte-secreted factors on granulosa and thecal cells, cultured independently and in co-culture, and the effect of stem cell factor (SCF); a granulosa cell derived peptide that appears to have multiple roles in follicle development. Granulosa and theca cells were isolated from 2–6 mm healthy follicles of mature porcine ovaries and cultured under serum-free conditions, supplemented with: 100 ng/ml LR3 IGF-1, 10 ng/ml insulin, 100 ng/ml testosterone, 0–10 ng/ml SCF, 1 ng/ml FSH (granulosa), 0.01 ng/ml LH (theca) or 1 ng/ml FSH and 0.01 ng/ml LH (co-culture) and with/without oocyte conditioned medium (OCM) or 5 oocytes. Cells were cultured in 96 well plates for 144 h, after which viable cell numbers were determined. Medium was replaced every 48 h and spent medium analysed for steroids. Oocyte secreted factors were shown to stimulate both granulosa cell proliferation (P < 0.001) and oestradiol production (P < 0.001) by granulosa cells throughout culture. In contrast, oocyte secreted factors suppressed granulosa cell progesterone production after both 48 and 144 hours (P < 0.001). Thecal cell numbers were increased by oocyte secreted factors (P = 0.02), together with a suppression in progesterone and androstenedione synthesis after 48 hours (P < 0.001) and after 144 hours (P = 0.02), respectively. Oocyte secreted factors also increased viable cell numbers (P < 0.001) in co-cultures together with suppression of progesterone (P < 0.001) and oestradiol (P < 0.001). In granulosa cell only cultures, SCF increased progesterone production in a dose dependent manner (P < 0.001), whereas progesterone synthesis by theca cells was reduced in a dose dependent manner (P = 0.002). Co-cultured cells demonstrated an increase in progesterone production with increasing SCF dose (P < 0.001) and an increase in oestradiol synthesis at the highest dose of SCF (100 ng/ml). In summary, these findings demonstrate the presence of a co-ordinated paracrine interaction between somatic cells and germ cells, whereby oocyte derived signals interact locally to mediate granulosa and theca cell function. SCF has a role in modulating this local interaction. In conclusion, the oocyte is an effective modulator of granulosa-theca interactions, one role being the inhibition of luteinization

Evolutionary ecomorphology of the Falkland Islands wolf Dusicyon australis

The Falkland Islands wolf Dusicyon australis is an extinct canid that was once the only endemic terrestrial mammal to inhabit the Falkland Islands. There is still a puzzling picture of the morphological adaptations of this wolf that quickly evolved from its mainland fossil ancestor: Dusicyon avus. We employ a geometric morphometric approach to identify patterns of skull shape variation in extant canids and Dusicyon spp. The Falkland Islands wolf and its fossil ancestor show a more carnivorous feeding morphology than other South American foxes, and they cluster morphologically with jackals. This supports convergence in skull shape between Dusicyon and Old World canids, although the convergence is not as strong as that exhibited by their sister hyper- and hypocarnivorous taxa

Infrared composition of the Large Magellanic Cloud

The evolution of galaxies and the history of star formation in the Universe are among the most important topics in today's astrophysics. Especially, the role of small, irregular galaxies in the star-formation history of the Universe is not yet clear. Using the data from the AKARI IRC survey of the Large Magellanic Cloud at 3.2, 7, 11, 15, and 24 {\mu}m wavelengths, i.e., at the mid- and near-infrared, we have constructed a multiwavelength catalog containing data from a cross-correlation with a number of other databases at different wavelengths. We present the separation of different classes of stars in the LMC in color-color, and color-magnitude, diagrams, and analyze their contribution to the total LMC flux, related to point sources at different infrared wavelengths

Coastal clustering of HEV; Cornwall, UK.

PublishedBACKGROUND AND AIMS: Autochthonous hepatitis E virus (HEV) infection is a porcine zoonosis and increasingly recognized in developed countries. In most cases the route of infection is uncertain. A previous study showed that HEV was associated geographically with pig farms and coastal areas. AIM: The aim of the present research was to study the geographical, environmental and social factors in autochthonous HEV infection. METHODS: Cases of HEV genotype 3 infection and controls were identified from 2047 consecutive patients attending a rapid-access hepatology clinic. For each case/control the following were recorded: distance from home to nearest pig farm, distance from home to coast, rainfall levels during the 8 weeks before presentation, and socioeconomic status. RESULTS: A total of 36 acute hepatitis E cases, 170 age/sex-matched controls and 53 hepatitis controls were identified. The geographical spread of hepatitis E cases was not even when compared with both control groups. Cases were more likely to live within 2000 m of the coast (odds ratio=2.32, 95% confidence interval=1.08-5.19, P=0.03). There was no regional difference in the incidence of cases and controls between west and central Cornwall. There was no difference between cases and controls in terms of distance from the nearest pig farm, socioeconomic status or rainfall during the 8 weeks before disease presentation. CONCLUSION: Cases of HEV infection in Cornwall are associated with coastal residence. The reason for this observation is uncertain, but might be related to recreational exposure to beach areas exposed to HEV-contaminated 'run-off' from pig farms. This hypothesis merits further study.The European Centre for the Environment and Human Health (part of the Peninsula College of Medicine and Dentistry which is a joint entity of the University of Exeter, the University of Plymouth and the NHS in the South West) is supported by investment from the European Regional Development Fund and the European Social Fund Convergence Programme for Cornwall and the Isles of Scilly

Properties of Galaxies in and around Voids

Two surveys for intrinsically faint galaxies towards nearby voids have been conducted at the MPI f\"ur Astronomie, Heidelberg. One selected targets from a new diameter limited ($\Phi \ge 5''$) catalog with morphological criteria while the other used digitized objective prism Schmidt plates to select mainly HII dwarf galaxies. For some 450 galaxies, redshifts and other optical data were obtained. We studied the spatial distribution of the sample objects, their luminosity function, and their intrinsic properties. Most of the galaxies belong to already well known sheets and filaments. But we found about a dozen highly isolated galaxies in each sample (nearest neighborhood distance $\ge 3 h_{75}^{-1} Mpc$). These tend to populate additional structures and are not distributed homogeneously throughout the voids. As our results on 'void galaxies' still suffer from small sample statistics, I also tried to combine similar existing surveys of nearby voids to get further hints on the larger structure and on the luminosity function of the isolated galaxies. No differences in the luminosity function of sheet and void galaxies could be found. The optical and infrared properties of both samples are in the normal range for samples dominated by late-type dwarfs. Follow-up HI studies show that the isolated dwarfs in both samples have unusual high amount of neutral gas for a given luminosity.Comment: 10 pages, 4 figures, latex, to appear in the proceedings of the 'Ringberg workshop on Large Scale Structure', hold Sep. 23-28, 199

The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts

The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al

Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc

Relationship between knee and ankle degeneration in a population of organ donors

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is a progressive degenerative condition of synovial joints in response to both internal and external factors. The relationship of OA in one joint of an extremity to another joint within the same extremity, or between extremities, has been a topic of interest in reference to the etiology and/or progression of the disease.</p> <p>Methods</p> <p>The prevalence of articular cartilage lesions and osteophytes, characteristic of OA, was evaluated through visual inspection and grading in 1060 adult knee/tali pairs from 545 cadaveric joint donors.</p> <p>Results</p> <p>Joint degeneration increased more rapidly with age for the knee joint, and significantly more knee joints displayed more severe degeneration than ankle joints from as early as the third decade. Women displayed more severe knee degeneration than did men. Severe ankle degeneration did not exist in the absence of severe knee degeneration. The effect of weight on joint degeneration was joint-specific whereby weight had a significantly greater effect on the knee. Ankle grades increasingly did not match within a donor as the grade of degeneration in either the left or the right knee increased.</p> <p>Conclusions</p> <p>Gender and body type have a greater effect on knee joint integrity as compared to the ankle, suggesting that knees are more prone to internal causative effects of degeneration. We hypothesize that the greater variability in joint health between joints within an individual as disease progresses from normal to early signs of degeneration may be a result of mismatched limb kinetics, which in turn might lead to joint disease progression.</p

The fate of steroid estrogens: Partitioning during wastewater treatment and onto river sediments

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Springer Science+Business Media B.V.The partitioning of steroid estrogens in wastewater treatment and receiving waters is likely to influence their discharge to, and persistence in, the environment. This study investigated the partitioning behaviour of steroid estrogens in both laboratory and field studies. Partitioning onto activated sludge from laboratory-scale Husmann units was rapid with equilibrium achieved after 1 h. Sorption isotherms and Kd values decreased in the order 17α-ethinyl estradiol > 17α-estradiol > estrone > estriol without a sorption limit being achieved (1/n >1). Samples from a wastewater treatment works indicated no accumulation of steroid estrogens in solids from primary or secondary biological treatment, however, a range of steroid estrogens were identified in sediment samples from the River Thames. This would indicate that partitioning in the environment may play a role in the long-term fate of estrogens, with an indication that they will be recalcitrant in anaerobic conditions.EPSR