Variation in the ovarian reserve Is linked to alterations in intrafollicular estradiol production and ovarian biomarkers of follicular differentiation and oocyte quality in cattle

The mechanisms whereby the high variation in numbers of morphologically healthy oocytes and follicles in ovaries (ovarian reserve) may have an impact onovarian function, oocyte quality, and fertility are poorly understood. The objective was to determine whether previously validated biomarkers for follicular differentiation and function, as well as oocyte quality differed between cattle with low versus a high antral follicle count (AFC). Ovaries were removed (n = 5 per group) near the beginning of the nonovulatory follicular wave, before follicles could be identified via ultrasonography as being dominant, from heifers with high versus a low AFC. The F1, F2, and F3 follicles were dissected and diameters determined. Follicular fluid and thecal, granulosal, and cumulus cells and the oocyte were isolated and subjected to biomarker analyses. Although the size and numerous biomarkers of differentiation, such as mRNAs for the gonadotropin receptors, were similar, intrafollicular concentrations of estradiol and the abundance of mRNAs for CYP19A1 in granulosal cells and ESR1, ESR2, and CTSB in cumulus cells were greater, whereas mRNAs for AMH in granulosal cells and TBC1D1 in thecal cells were lower for animals with low versus a high AFC during follicle waves. Hence, variation in the ovarian reserve may have an impact on follicular function and oocyte quality via alterations in intrafollicular estradiol production and expression of key genes involved in follicle-stimulating hormone action (AMH) and estradiol (CYP19A1) production by granulosal cells, function and survival of thecal cells (TBC1D1), responsiveness of cumulus cells to estradiol (ESR1, ESR2), and cumulus cell determinants of oocyte quality (CTSB).

A role for Notch signaling in human corneal epithelial cell differentiation and proliferation

PURPOSE. To identify the role of Notch signaling in the human corneal epithelium. METHODS. Localization of Notch1, Notch2, Delta1, and Jagged1 in the human corneal epithelium was observed with the use of indirect immunofluorescence microscopy. Gene and protein expression of Notch receptors and ligands in human corneal epithelial cells was determined by RT-PCR and Western blot analysis, respectively. The effects of Notch inhibition (by {gamma}-secretase inhibition) and activation (by recombinant Jagged1) on epithelial cell proliferation (Ki67) and differentiation (CK3) were analyzed after Western blotting and immunocytochemistry. RESULTS. Immunofluorescent labeling localized Notch1 and Notch2 to suprabasal epithelial cell layers, whereas Delta1 and Jagged1 were observed throughout the corneal epithelium. Notch1, Notch2, Delta1, and Jagged1 genes and proteins were expressed in human corneal epithelial cells. {gamma}-Secretase inhibition resulted in decreased Notch1 and Notch2 expression, with an accompanying decrease in Ki67 and increased CK3 expression. The activation of Notch by Jagged1 resulted in the upregulation of active forms of Notch1 and 2 proteins (P < 0.05), with a concurrent increase in Ki67 (P < 0.05) and a decrease in CK3 (P < 0.05) expression. Interestingly, {gamma}-secretase inhibition in a three-dimensional, stratified corneal epithelium equivalent had no effect on Ki67 or CK3 expression. In contrast, Jagged1 activation resulted in decreased CK3 expression (P < 0.05), though neither Notch activation nor inhibition affected cell proliferation in the 3D tissue equivalent. CONCLUSIONS. Notch family members and ligands are expressed in the human corneal epithelium and appear to play pivotal roles in corneal epithelial cell differentiation.

Think local, act local? Issues of co-ordination and integration in Local Agenda 21

The political response to the complex package of environmental problems which threaten the future of our planet has been to introduce a new agenda of environmental action based on the principles of sustainability and subsidiarity. This has been crystallised in world agreements signed at the Earth Summit in Rio. One of these, Agenda 21, calls for the governments and communities of the world to prepare action plans for their areas which can build consensus between the various stakeholder groups and feed the principles of sustainable development back into their policies and day-to-day practices. This paper explores the experience of Local Agenda 21 type processes at three levels in the South East of England: the regional, county (sub-regional) and local level. In particular it undertakes a critical appraisal of the success of these participatory and consensus-building exercises in developing an integrated and co-ordinated approach to environmental action planning. It concludes that, although much useful work has been done in raising awareness and modifying policy and practice, there are significant cultural and institutional barriers which are hindering progress.

The UK Department of National Heritage: a model for the development and integration of leisure policy in the new Europe?

Leisure is in the vanguard of a social and cultural revolution which is replacing the former East/West political bipolarity with a globalised economic system in which the new Europe has a central rôle. Within this revolution, leisure, including recreation, culture and tourism, is constructed as the epitome of successful capitalist development; the very legitimisation of the global transmogrification from a production to a consumption orientation. While acting as a direct encouragement to the political transformation in many eastern European states, it is uncertain how the issue of leisure policy is being handled, given its centrality to the new economic order. This paper therefore examines the experience of western Europe, considering in particular the degree to which the newly-created Department of National Heritage in the UK provides a potential model for leisure development and policy integration in the new Europe. Despite an official rhetoric of support and promotion of leisure activities, reflecting the growing economic significance of tourism and the positive relationship between leisure provision and regional economic development, the paper establishes that in the place of the traditional rôle of the state in promoting leisure interests, the introduction of the Department has signified a shift to the use of leisure to promote the Government's interests, particularly in regenerating citizen rights claims towards the market. While an institution such as the Department of National Heritage may have relevance to emerging states as a element in the maintenance of political hegemony, therefore, it is questionable how far it can be viewed as a promoter or protector of leisure as a signifier of a newly-won political, economic and cultural freedom throughout Europe.

TRIM32 regulates skeletal muscle stem cell differentiation and is necessary for normal adult muscle regeneration

Limb girdle muscular dystrophy type 2H (LGMD2H) is an inherited autosomal recessive disease of skeletal muscle caused by a mutation in the TRIM32 gene. Currently its pathogenesis is entirely unclear. Typically the regeneration process of adult skeletal muscle during growth or following injury is controlled by a tissue specific stem cell population termed satellite cells. Given that TRIM32 regulates the fate of mammalian neural progenitor cells through controlling their differentiation, we asked whether TRIM32 could also be essential for the regulation of myogenic stem cells. Here we demonstrate for the first time that TRIM32 is expressed in the skeletal muscle stem cell lineage of adult mice, and that in the absence of TRIM32, myogenic differentiation is disrupted. Moreover, we show that the ubiquitin ligase TRIM32 controls this process through the regulation of c-Myc, a similar mechanism to that previously observed in neural progenitors. Importantly we show that loss of TRIM32 function induces a LGMD2H-like phenotype and strongly affects muscle regeneration in vivo. Our studies implicate that the loss of TRIM32 results in dysfunctional muscle stem cells which could contribute to the development of LGMD2H.

Spectral theory of Toeplitz and Hankel operators on the Bergman space A1

The Fredholm properties of Toeplitz operators on the Bergman space A2 have been well-known for continuous symbols since the 1970s. We investigate the case p=1 with continuous symbols under a mild additional condition, namely that of the logarithmic vanishing mean oscillation in the Bergman metric. Most differences are related to boundedness properties of Toeplitz operators acting on Ap that arise when we no longer have 1operators on A1 were characterized completely very recently but only for bounded symbols. We also consider compactness of Hankel operators on A1.

Femtosecond pulse shaping using differential evolutionary algorithm and wavelet operators

Evolutionary meta-algorithms for pulse shaping of broadband femtosecond duration laser pulses are proposed. The genetic algorithm searching the evolutionary landscape for desired pulse shapes consists of a population of waveforms (genes), each made from two concatenated vectors, specifying phases and magnitudes, respectively, over a range of frequencies. Frequency domain operators such as mutation, two-point crossover average crossover, polynomial phase mutation, creep and three-point smoothing as well as a time-domain crossover are combined to produce fitter offsprings at each iteration step. The algorithm applies roulette wheel selection; elitists and linear fitness scaling to the gene population. A differential evolution (DE) operator that provides a source of directed mutation and new wavelet operators are proposed. Using properly tuned parameters for DE, the meta-algorithm is used to solve a waveform matching problem. Tuning allows either a greedy directed search near the best known solution or a robust search across the entire parameter space.

Casimirs and Lax operators from the structure of Lie algebras

This paper uses the structure of the Lie algebras to identify the Casimir invariant functions and Lax operators for matrix Lie groups. A novel mapping is found from the cotangent space to the dual Lie algebra which enables Lax operators to be found. The coordinate equations of motion are given in terms of the structure constants and the Hamiltonian.

Applying Jackson’s methodological ideal-types: problems of differentiation and classification

In The Conduct of Inquiry in International Relations, Patrick Jackson situates methodologies in International Relations in relation to their underlying philosophical assumptions. One of his aims is to map International Relations debates in a way that ‘capture[s] current controversies’ (p. 40). This ambition is overstated: whilst Jackson’s typology is useful as a clarificatory tool, (re)classifying existing scholarship in International Relations is more problematic. One problem with Jackson’s approach is that he tends to run together the philosophical assumptions which decisively differentiate his methodologies (by stipulating a distinctive warrant for knowledge claims) and the explanatory strategies that are employed to generate such knowledge claims, suggesting that the latter are entailed by the former. In fact, the explanatory strategies which Jackson associates with each methodology reflect conventional practice in International Relations just as much as they reflect philosophical assumptions. This makes it more difficult to identify each methodology at work than Jackson implies. I illustrate this point through a critical analysis of Jackson’s controversial reclassification of Waltz as an analyticist, showing that whilst Jackson’s typology helps to expose inconsistencies in Waltz’s approach, it does not fully support the proposed reclassification. The conventional aspect of methodologies in International Relations also raises questions about the limits of Jackson’s ‘engaged pluralism’.

Fractional order and non-linear system identification algorithms for biomedical applications

We discuss the modelling of dielectric responses of amorphous biological samples. Such samples are commonly encountered in impedance spectroscopy studies as well as in UV, IR, optical and THz transient spectroscopy experiments and in pump-probe studies. In many occasions, the samples may display quenched absorption bands. A systems identification framework may be developed to provide parsimonious representations of such responses. To achieve this, it is appropriate to augment the standard models found in the identification literature to incorporate fractional order dynamics. Extensions of models using the forward shift operator, state space models as well as their non-linear Hammerstein-Wiener counterpart models are highlighted. We also discuss the need to extend the theory of electromagnetically excited networks which can account for fractional order behaviour in the non-linear regime by incorporating nonlinear elements to account for the observed non-linearities. The proposed approach leads to the development of a range of new chemometrics tools for biomedical data analysis and classification.