Local roles of TGF-beta superfamily members in the control of ovarian follicle development

Members of the transforming growth factor-beta (TGF-beta) superfamily have wide-ranging influences on many tissue and organ systems including the ovary. Two recently discovered TGF-beta superfamily members, growth/differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15; also designated as GDF-9B) are expressed in an oocyte-specific manner from a very early stage and play a key role in promoting follicle growth beyond the primary stage. Follicle growth to the small antral stage does not require gonadotrophins but appears to be driven by local autocrine/paracrine signals from both somatic cell types (granulosa and theca) and from the oocyte. TGF-beta superfamily members expressed by follicular cells and implicated in this phase of follicle development include TGF-beta, activin, GDF-9/9B and several BMPs. Acquisition of follicle-stimulating hormone (FSH) responsiveness is a pre-requisite for growth beyond the small antral stage and evidence indicates an autocrine role for granulosa-derived activin in promoting granulosa cell proliferation, FSH receptor expression and aromatase activity. Indeed, some of the effects of FSH on granulosa cells may be mediated by endogenous activin. At the same time, activin may act on theca cells to attenuate luteinizing hormone (LH)-dependent androgen production in small to medium-size antral follicles. Dominant follicle selection appears to depend on differential FSH sensitivity amongst a growing cohort of small antral follicles. Activin may contribute to this selection process by sensitizing those follicles with the highest "activin tone" to FSH. Production of inhibin, like oestradiol, increases in selected dominant follicles, in an FSH- and insulin-like growth factor-dependent manner and may exert a paracrine action on theca cells to upregulate LH-induced secretion of androgen, an essential requirement for further oestradiol secretion by the pre-ovulatory follicle. Like activin, BMP-4 and -7 (mostly from theca), and BMP-6 (mostly from oocyte), can enhance oestradiol and inhibin secretion by bovine granulosa cells while suppressing progesterone secretion; this suggests a functional role in delaying follicle luteinization and/or atresia. Follistatin, on the other hand, may favor luteinization and/or atresia by bio-neutralizing intrafollicular activin and BMPs. Activin receptors are expressed by the oocyte and activin may have a further intrafollicular role in the terminal stages of follicle differentiation to promote oocyte maturation and developmental competence. In a reciprocal manner, oocyte-derived GDF-9/9B may act on the surrounding cumulus granulosa cells to attenuate oestradiol output and promote progesterone and hyaluronic acid production, mucification and cumulus expansion.(C) 2003 Elsevier Science B.V. All rights reserved.

Effects of copper on the antioxidant activity of olive polyphenols in bulk oil and oil-in-water emulsions

The antioxidant activity and interactions with copper of four olive oil phenolic compounds, namely oleuropein, hydroxytyrosol, 3,4- dihydroxyphenylethanol- elenolic acid ( 1), and 3,4- dihydroxyphenyl-ethanolelenolic acid dialdehyde ( 2), in olive oil and oil- in- water emulsions stored at 60 degrees C were studied. All four phenolic compounds significantly extended the induction time of lipid oxidation in olive oil with the order of activity being hydroxytyrosol > compound 1 > compound 2 > oleuropein > alpha- tocopherol; but in the presence of Cu( II), the stability of oil samples containing phenolic compounds decreased by at least 90%, and the antioxidant activity of hydroxytyrosol and compounds 1 and 2 became similar. In oil- in- water emulsions prepared from olive oil stripped of tocopherols, hydroxytyrosol enhanced the prooxidant effect of copper at pH 5.5 but not at pH 7.4. The stability of samples containing copper at pH 5.5 was not significantly different if oleuropein was present from that of the control. Oleuropein at pH 7.4, and compounds 1 and 2 at both pH values tested, reduced the prooxidant effect of copper. The lower stability and the higher reducing capacity of all compounds at pH 7.4 could not explain the higher stability of emulsions containing phenolic compounds at this pH value. However, mixtures containing hydroxytyrosol or oleuropein with copper showed higher 1,1-diphenyl- 2- picrylhydrazyl radical scavenging activity at pH 7.4 than at pH 5.5. Moreover, the compound 2- copper complex showed higher radical scavenging activity then the uncomplexed compound at pH 5.5. It can be concluded that the formation of a copper complex with radical scavenging activity is a key step in the antioxidant action of the olive oil phenolic compounds in an emulsion containing copper ions.

The effects of paeonol on the electrophysiological properties of cardiac ventricular myocytes

Previous studies have shown that "Mudanpi", a Chinese herbal medicine, has a significant cardioprotective effect against myocardial ischaemia. Based on these findings we hypothesised that paeonol, the main component of Mudanpi, might have an effect on the cellular electrophysiology of cardiac ventricular myocytes. The effects of paeonol on the action potential and ion channels of cardiac ventricular myocytes were studied using the standard whole-cell configuration of the patch-clamp technique. Ventricular myocytes were isolated from the hearts of adult guinea-pig by enzymic dispersion. The myocytes were continuously perfused with various experimental solutions at room temperature and paeonol applied in the perfusate. Action potentials and membrane currents were recorded using both current and voltage clamp modes of the patch-clamp technique. Paeonol, at concentrations 160 mu M and 640 mu M, decreased the action potential upstroke phase, an action associated with the blockade of the voltage-gated, fast sodium channel. The effects of paeonol on both action potential and Na+ current were concentration dependent. Paeonol had a high affinity for inactivated sodium channels. Paeonol also shortened the action potential duration, in a manner not associated with the blockade of the calcium current, or the enhancement of potassium currents. These findings suggest that paeonol, and therefore Mudanpi, may possess antiarrhythmic activity, which may confer its cardioprotective effects. (c) 2006 Elsevier B.V All rights reserved.

The role of visual and nonvisual information in the control of locomotion

During locomotion, retinal flow, gaze angle, and vestibular information can contribute to one's perception of self-motion. Their respective roles were investigated during active steering: Retinal flow and gaze angle were biased by altering the visual information during computer-simulated locomotion, and vestibular information was controlled through use of a motorized chair that rotated the participant around his or her vertical axis. Chair rotation was made appropriate for the steering response of the participant or made inappropriate by rotating a proportion of the veridical amount. Large steering errors resulted from selective manipulation of retinal flow and gaze angle, and the pattern of errors provided strong evidence for an additive model of combination. Vestibular information had little or no effect on steering performance, suggesting that vestibular signals are not integrated with visual information for the control of steering at these speeds.

For better or worse: the effect of levodopa on speech in Parkinson's disease

While the beneficial effect of levodopa on traditional motor control tasks have been well documented over the decades. its effect on speech motor control has rarely been objectively examined and the existing literature remains inconclusive. This paper aims to examine the effect of levodopa on speech in patients with Parkinson's disease. It was hypothesized that levodopa would improve preparatory motor set related activity and alleviate hypophonia. Patients fasted and abstained from levodopa overnight. Motor examination and speech testing was performed the following day, pre-levodopa during their "off' state, then at hourly intervals post-medication to obtain the best "on" state. All speech stimuli showed a consistent tendency for increased loudness and faster rate during the "on" state, but this was accompanied by a greater extent of intensity decay. Pitch and articulation remained unchanged. Levodopa effectively upscaled the overall gain setting of vocal amplitude and tempo, similar to its well-known effect on limb movement. However, unlike limb movement, this effect on the final acoustic product of speech may or may not be advantageous, depending on the existing speech profile of individual patients. (C) 2007 Movement Disorder Society.

Neural systems in the visual control of steering

Visual control of locomotion is essential for most mammals and requires coordination between perceptual processes and action systems. Previous research on the neural systems engaged by self-motion has focused on heading perception, which is only one perceptual subcomponent. For effective steering, it is necessary to perceive an appropriate future path and then bring about the required change to heading. Using function magnetic resonance imaging in humans, we reveal a role for the parietal eye fields (PEFs) in directing spatially selective processes relating to future path information. A parietal area close to PEFs appears to be specialized for processing the future path information itself. Furthermore, a separate parietal area responds to visual position error signals, which occur when steering adjustments are imprecise. A network of three areas, the cerebellum, the supplementary eye fields, and dorsal premotor cortex, was found to be involved in generating appropriate motor responses for steering adjustments. This may reflect the demands of integrating visual inputs with the output response for the control device.

Fusing data-mining and knowledge elicitation for the supervisory control of an aluminium plate mill

Knowledge-elicitation is a common technique used to produce rules about the operation of a plant from the knowledge that is available from human expertise. Similarly, data-mining is becoming a popular technique to extract rules from the data available from the operation of a plant. In the work reported here knowledge was required to enable the supervisory control of an aluminium hot strip mill by the determination of mill set-points. A method was developed to fuse knowledge-elicitation and data-mining to incorporate the best aspects of each technique, whilst avoiding known problems. Utilisation of the knowledge was through an expert system, which determined schedules of set-points and provided information to human operators. The results show that the method proposed in this paper was effective in producing rules for the on-line control of a complex industrial process.

In vitro examination of the effect of Orlistat on the ability of the faecal microbiota to utilize dietary lipids

Orlistat is an anti-obesity treatment with which several gastrointestinal (GI) side-effects are commonly associated in the initial stages of therapy. There is no physiological explanation as to why two-thirds of those who take the drug experience one or more side-effects. It has been hypothesized that the GI microbiota may protect from or contribute to these GI disturbances. Using in vitro batch culture and human gut model systems, studies were conducted to determine whether increased availability of dietary lipids and/or orlistat affect the composition and/or activity of the faecal microbiota. Results from 24-h batch culture fermentation experiments demonstrated no effect of orlistat in the presence or absence of a dietary lipid (olive oil) on the composition of bacterial communities [as determined by fluorescence in situ hybridization (FISH) and denaturing gradient gel electrophoresis (DGGE) analyses], but did show there was great variability in the lipolytic activities of the microbiotas of individuals, as determined by gas chromatography analysis of long-chain fatty acids in samples. Subsequent studies focused on the effect of orlistat in the presence and absence of lipid in in vitro human gut model systems. Systems were run for 14 days with gut model medium (GMM) only (to steady state, SS), then fed at 12-h intervals with 50 mg orlistat, 2 g olive oil or a mixture of both for 14 days. FISH and DGGE were used to monitor changes in bacterial populations. Bacteria were cultivated from the GMM only (control) systems at SS. All strains isolated were screened for lipolytic activity using tributyrin agar. FISH and DGGE demonstrated that none of the compounds (singly or in combination) added to the systems had any notable effect on microbial population dynamics for any of the donors, although Subdoligranulum populations appeared to be inhibited by orlistat in the presence or absence of lipid. Orlistat had little or no effect on the metabolism of indigenous and added lipids in the fermentation systems, but there was great variability in the way the faecal microbiotas of the donors were able to degrade added lipids. Variability in lipid degradation could be correlated with the number and activity of isolated lipolytic bacteria. The mechanism by which orlistat and the GI microbiota cause side-effects in individuals is unknown, but several hypotheses have been proposed to account for their manifestation. The demonstration of great variability in the lipolytic activity of microbiotas to degrade lipids led to a large-scale cultivation-based study of lipolytic/lipase-positive bacteria present in the human faecal microbiota. Of 4,000 colonies isolated from 15 donors using five different agars, 378 strains were identified that had lipase activity. Molecular identification of strains isolated from five donors demonstrated that lipase activity is more prevalent in the human GI microbiota than previously thought, with members of the phyla Firmicutes, Bacteroidetes and Actinobacteria identified. Molecular identification and characterization of the substrate specificities of the strains will be carried out as part of ongoing work.

A hyperstable neural network for the modelling and control of nonlinear systems

A multivariable hyperstable robust adaptive decoupling control algorithm based on a neural network is presented for the control of nonlinear multivariable coupled systems with unknown parameters and structure. The Popov theorem is used in the design of the controller. The modelling errors, coupling action and other uncertainties of the system are identified on-line by a neural network. The identified results are taken as compensation signals such that the robust adaptive control of nonlinear systems is realised. Simulation results are given.

Using self-organising feature maps for the control of artificial organisms

Variations on the standard Kohonen feature map can enable an ordering of the map state space by using only a limited subset of the complete input vector. Also it is possible to employ merely a local adaptation procedure to order the map, rather than having to rely on global variables and objectives. Such variations have been included as part of a hybrid learning system (HLS) which has arisen out of a genetic-based classifier system. In the paper a description of the modified feature map is given, which constitutes the HLSs long term memory, and results in the control of a simple maze running task are presented, thereby demonstrating the value of goal related feedback within the overall network.

The effect of the year of wheat variety release on productivity and stability of performance on two organic and two non-organic farms

Nineteen wheat cultivars, released from 1934 to 2000, were grown at two organic and two non-organic sites in each of 3 years. Assessments included grain yield, grain protein concentration, protein yield, disease incidence and green leaf area. The superiority of each cultivar (the sum of the squares of the differences between its mean in each environment and the mean of the best cultivar there, divided by twice the number of environments; CS) was calculated for yield, grain protein concentration and protein yield, and ranked in each environment. The yield and grain protein concentration CS were more closely correlated with cultivar release date at the non-organic sites than at organic sites. This difference may be attributed to higher yield levels with larger differences among cultivars at the non-organic sites, rather than to improved stability (i.e. similar ranks) across sites. The significant difference in the correlation of protein yield CS and cultivar age between organic and non-organic sites would support evidence that the ability to take up mineral nitrogen (N) compared to soil N has been a component of the selection conditions of more modern cultivars (released after 1989). This is supported by assessment of green leaf area (GLA), where more modern cultivars in the non-organic systems had greater late-season GLA, a trend that was not identified in organic conditions. This effect could explain the poor correlation between age and protein yield CS in organic compared to non-organic conditions where modern cultivars are selected to benefit from later nitrogen (N) availability which includes the spring nitrogen applications tailored to coincide with peak crop demand. Under organic management, N release is largely based on the breakdown of fertility-building crops incorporated (ploughed-in) in the previous autumn. The release of nutrients from these residues is dependent on the soil conditions, which includes temperature and microbial populations, in addition to the potential leaching effect of high winter rainfall in the UK. In organic cereal crops, early resource capture is a major advantage for maximizing the utilization of nutrients from residue breakdown. It is concluded that selection of cultivars under conditions of high agrochemical inputs selects for cultivars that yield well under maximal conditions in terms of nutrient availability and pest, disease and weed control. The selection conditions for breeding have a tendency to select cultivars which perform relatively better in non-organic compared to organic systems.

Modelling and control of Hammerstein system using B-spline approximation and the inverse of De Boor algorithm

In this article a simple and effective controller design is introduced for the Hammerstein systems that are identified based on observational input/output data. The nonlinear static function in the Hammerstein system is modelled using a B-spline neural network. The controller is composed by computing the inverse of the B-spline approximated nonlinear static function, and a linear pole assignment controller. The contribution of this article is the inverse of De Boor algorithm that computes the inverse efficiently. Mathematical analysis is provided to prove the convergence of the proposed algorithm. Numerical examples are utilised to demonstrate the efficacy of the proposed approach.

Internal model control of nonlinear systems through the inversion of recurrent neural networks

Recurrent neural networks can be used for both the identification and control of nonlinear systems. This paper takes a previously derived set of theoretical results about recurrent neural networks and applies them to the task of providing internal model control for a nonlinear plant. Using the theoretical results, we show how an inverse controller can be produced from a neural network model of the plant, without the need to train an additional network to perform the inverse control.

The control of dynamical systems by neural networks

In this paper the use of neural networks for the control of dynamical systems is considered. Both identification and feedback control aspects are discussed as well as the types of system for which neural networks can provide a useful technique. Multi-layer Perceptron and Radial Basis function neural network types are looked at, with an emphasis on the latter. It is shown how basis function centre selection is a critical part of the implementation process and that multivariate clustering algorithms can be an extremely useful tool for finding centres.

Detecting an impact of predation on bird populations depends on the methods used to assess the predators

Summary 1. In recent decades there have been population declines of many UK bird species, which have become the focus of intense research and debate. Recently, as the populations of potential predators have increased there is concern that increased rates of predation may be contributing to the declines. In this review, we assess the methodologies behind the current published science on the impacts of predators on avian prey in the UK. 2. We identified suitable studies, classified these according to study design (experimental ⁄observational) and assessed the quantity and quality of the data upon which any variation in predation rates was inferred. We then explored whether the underlying study methodology had implications for study outcome. 3. We reviewed 32 published studies and found that typically observational studies comprehensively monitored significantly fewer predator species than experimental studies. Data for a difference in predator abundance from targeted (i.e. bespoke) census techniques were available for less than half of the 32 predator species studied. 4. The probability of a study detecting an impact on prey abundance was strongly, positively related to the quality and quantity of data upon which the gradient in predation rates was inferred. 5. The findings suggest that if a study is based on good quality abundance data for a range of predator species then it is more likely to detect an effect than if it relies on opportunistic data for a smaller number of predators. 6. We recommend that the findings from studies which use opportunistic data, for a limited number of predator species, should be treated with caution and that future studies employ bespoke census techniques to monitor predator abundance for an appropriate suite of predators.