Germ cells enter meiosis in a rostro-caudal wave during development of the mouse ovary

Germ cells in the mouse embryo remain undifferentiated until about 13.5 days post-coitum (dpc), when male germ cells enter mitotic arrest and female germ cells enter meiosis. The molecular signals and transcriptional control mechanisms governing the differential fate of germ cells in males and females remain largely unknown. In order to gain insights into the behavior of germ cells around this period and into likely mechanisms controlling entry into meiosis, we have studied by wholemount in situ hybridization the expression pattern of two germ cell-specific markers, Oct4 and Sycp3, during mouse fetal gonad development. We observed a dynamic wave of expression of both genes in developing ovaries, with Oct4 expression being extinguished in a rostro-caudal wave and Sycp3 being upregulated in a corresponding wave, during the period 13.5-15.5 dpc. These results indicate that entry into meiosis proceeds in a rostro-caudal progression, in turn suggesting that somatically derived signals may contribute to the control of germ cell entry into meiosis in developing ovaries. (C) 2004 Wiley-Liss, Inc.

Novel strategies in feedforward adaptation to a position-dependent perturbation

To investigate the control mechanisms used in adapting to position-dependent forces, subjects performed 150 horizontal reaching movements over 25 cm in the presence of a position-dependent parabolic force field (PF). The PF acted only over the first 10 cm of the movement. On every fifth trial, a virtual mechanical guide (double wall) constrained subjects to move along a straight-line path between the start and target positions. Its purpose was to register lateral force to track formation of an internal model of the force field, and to look for evidence of possible alternative adaptive strategies. The force field produced a force to the right, which initially caused subjects to deviate in that direction. They reacted by producing deviations to the left, into the force field, as early as the second trial. Further adaptation resulted in rapid exponential reduction of kinematic error in the latter portion of the movement, where the greatest perturbation to the handpath was initially observed, whereas there was little modification of the handpath in the region where the PF was active. Significant force directed to counteract the PF was measured on the first guided trial, and was modified during the first half of the learning set. The total force impulse in the region of the PF increased throughout the learning trials, but it always remained less than that produced by the PF. The force profile did not resemble a mirror image of the PF in that it tended to be more trapezoidal than parabolic in shape. As in previous studies of force-field adaptation, we found that changes in muscle activation involved a general increase in the activity of all muscles, which increased arm stiffness, and selectively-greater increases in the activation of muscles which counteracted the PF. With training, activation was exponentially reduced, albeit more slowly than kinematic error. Progressive changes in kinematics and EMG occurred predominantly in the region of the workspace beyond the force field. We suggest that constraints on muscle mechanics limit the ability of the central nervous system to employ an inverse dynamics model to nullify impulse-like forces by generating mirror-image forces. Consequently, subjects adopted a strategy of slightly overcompensating for the first half of the force field, then allowing the force field to push them in the opposite direction. Muscle activity patterns in the region beyond the boundary of the force field were subsequently adjusted because of the relatively-slow response of the second-order mechanics of muscle impedance to the force impulse.

Characterization of a strong, constitutive mung bean (Vigna radiata L.) promoter with a complex mode of regulation in planta

We report the cloning and characterization in tobacco and Arabidopsis of a Vigna radiata L. (mung bean) promoter that controls the expression of VR-ACS1, an auxin-inducible ACC synthase gene. The VR-ACS1 promoter exhibits a very unusual behavior when studied in plants different from its original host, mung bean. GUS and luciferase in situ assays of transgenic plants containing VR-ACS1 promoter fusions show strong constitutive reporter gene expression throughout tobacco and Arabidopsis development. In vitro quantitative analyses show that transgenic plants harboring VR-ACS1 promoter-reporter constructs have on average 4-6 fold higher protein and activity levels of both reporter genes than plants transformed with comparable CaMV 35S promoter fusions. Similar transcript levels are present in VR-ACS1 and CaMV 35S promoter lines, suggesting that the high levels of gene product observed for the VR-ACS1 promoter are the combined result of transcriptional and translational activation. All tested deletion constructs retaining the core promoter region can drive strong constitutive promoter activity in transgenic plants. This is in contrast to mung bean, where expression of the native VR-ACS1 gene is almost undetectable in plants grown under normal conditions, but is rapidly and highly induced by a variety of stimuli. The constitutive behavior of the VR-ACS1 promoter in heterologous hosts is surprising, suggesting that the control mechanisms active in mung bean are impaired in tobacco and Arabidopsis. The 'aberrant' behavior of the VR-ACS1 promoter is further emphasized by its failure to respond to auxin and cycloheximide in heterologous hosts. VR-ACS1 promoter regulatory mechanisms seem to be different from all previously characterized auxin-inducible promoters.

Attentional changes in pre-stimulus oscillatory activity within early visual cortex are predictive of human visual performance

Physiological and neuroimaging studies provide evidence to suggest that attentional mechanisms operating within the fronto-parietal network may exert top–down control on early visual areas, priming them for forthcoming sensory events. The believed consequence of such priming is enhanced task performance. Using the technique of magnetoencephalography (MEG), we investigated this possibility by examining whether attention-driven changes in cortical activity are correlated with performance on a line-orientation judgment task. We observed that, approximately 200 ms after a covert attentional shift towards the impending visual stimulus, the level of phase-resetting (transient neural coherence) within the calcarine significantly increased for 2–10 Hz activity. This was followed by a suppression of alpha activity (near 10 Hz) which persisted until the onset of the stimulus. The levels of phase-resetting, alpha suppression and subsequent behavioral performance varied between subjects in a systematic fashion. The magnitudes of phase-resetting and alpha-band power were negatively correlated, with high levels of coherence associated with high levels of performance. We propose that top–down attentional control mechanisms exert their initial effects within the calcarine through a phase-resetting within the 2–10 Hz band, which in turn triggers a suppression of alpha activity, priming early visual areas for incoming information and enhancing behavioral performance.

Switching the mode of metabolism in the yeast Saccharomyces cerevisiae

The biochemistry of most metabolic pathways is conserved from bacteria to humans, although the control mechanisms are adapted to the needs of each cell type. Oxygen depletion commonly controls the switch from respiration to fermentation. However, Saccharomyces cerevisiae also controls that switch in response to the external glucose level. We have generated an S. cerevisiae strain in which glucose uptake is dependent on a chimeric hexose transporter mediating reduced sugar uptake. This strain shows a fully respiratory metabolism also at high glucose levels as seen for aerobic organisms, and switches to fermentation only when oxygen is lacking. These observations illustrate that manipulating a single step can alter the mode of metabolism. The novel yeast strain is an excellent tool to study the mechanisms underlying glucose-induced signal transduction. © 2004 European Molecular Biology Organization.

Implementing an adaptive TCP fairness while exploiting 802.11e over wireless mesh networks

Purpose: The purpose of this paper is to investigate the use of 802.11e MAC to resolve the transmission control protocol (TCP) unfairness. Design/methodology/approach: The paper shows how a TCP sender may adapt its transmission rate using the number of hops and the standard deviation of recently measured round-trip times to address the TCP unfairness. Findings: Simulation results show that the proposed techniques provide even throughput by providing TCP fairness as the number of hops increases over a wireless mesh network (WMN). Research limitations/implications: Future work will examine the performance of TCP over routing protocols, which use different routing metrics. Other future work is scalability over WMNs. Since scalability is a problem with communication in multi-hop, carrier sense multiple access (CSMA) will be compared with time division multiple access (TDMA) and a hybrid of TDMA and code division multiple access (CDMA) will be designed that works with TCP and other traffic. Finally, to further improve network performance and also increase network capacity of TCP for WMNs, the usage of multiple channels instead of only a single fixed channel will be exploited. Practical implications: By allowing the tuning of the 802.11e MAC parameters that have previously been constant in 802.11 MAC, the paper proposes the usage of 802.11e MAC on a per class basis by collecting the TCP ACK into a single class and a novel congestion control method for TCP over a WMN. The key feature of the proposed TCP algorithm is the detection of congestion by measuring the fluctuation of RTT of the TCP ACK samples via the standard deviation, plus the combined the 802.11e AIFS and CWmin allowing the TCP ACK to be prioritised which allows the TCP ACKs will match the volume of the TCP data packets. While 802.11e MAC provides flexibility and flow/congestion control mechanism, the challenge is to take advantage of these features in 802.11e MAC. Originality/value: With 802.11 MAC not having flexibility and flow/congestion control mechanisms implemented with TCP, these contribute to TCP unfairness with competing flows. © Emerald Group Publishing Limited.

An examination of the management of Russian civil society

This thesis begins by examining the concepts of civil society and social capital. Specifically, it outlines the role of health and education third sector organisations (TSOs) in building civil society and generating social capital which is conducive to democratisation. Following this, the thesis presents literature on civil society development in the context of the Russian Federation, highlighting a void in our understanding of health and education TSOs in this context. The literature review examines cultural-historic antecedents and their impact on civil society development. These antecedents result in three constraints which limit TSOs ability to establish civil society as an autonomous space. In light of these constraints, the thesis explores the present day realities faced by Russian TSOs and proposes that the all-dominant nature of the Russian state leads to managed civil society arrangements. Consequently the thesis addresses the question of how a managed civil society manifests itself in the context of the Russian Federation. Using a qualitative research design, the thesis investigates the control mechanisms created by legislative framework, the ability of third sector organisations to substitute for the state, and the organisational characteristics of TSOs within a managed civil society space. Based on interview data from 82 TSOs across three geographical regions, the empirical chapters explore these three aspects in-depth. Firstly, the thesis demonstrates how a specific legislative framework is used as a legally mandated method to manage civil society. Secondly, the thesis explores more subtle attempts by the state to manage civil society. And thirdly, the thesis highlights ways in which the state controls TSOs and coerces them to mimic marionette organisations. Overall, the evidence presented throughout the thesis highlights the idiosyncratic nature of managed civil society arrangements in Russia in which the state is able to control and direct civil society

Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to the development of pulmonary arterial hypertension

Aims: Pulmonary arterial hypertension [1] is a proliferative disorder associated with enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMCs). Reactive oxygen species (ROS) is implicated in the development of PAH and regulates the vascular tone and functions. However, which cellular signaling mechanisms are triggered by ROS in PAH is still unknown. Hence, here we wished to characterize the signaling mechanisms triggered by ROS. Methods and Results: By Western blots, we showed that increased intracellular ROS caused inhibition of the glycolytic pyruvate kinase M2 (PKM2) activity through promoting the phosphorylation of PKM2. Monocrotaline (MCT)-induced rats developed severe PAH and right ventricular hypertrophy, with a significant increase in the P-PKM2 and decrease in pyruvate kinase activity which could be attenuated with the treatments of PKM2 activators, FBP and l-serine. The antioxidant NAC, apocynin and MnTBAP had the similar protective effects in the development of PAH. In vitro assays confirmed that inhibition of PKM2 activity could modulate the flux of glycolytic intermediates in support of cell proliferation through the increased pentose phosphate pathway (PPP). Increased ROS and decreased PKM2 activity also promoted the Cav1.2 expression and intracellular calcium. Conclusion: Our data provide new evidence that PKM2 makes a critical regulatory contribution to the PAHs for the first time. Decreased pyruvate kinase M2 activity confers additional advantages to rat PASMCs by allowing them to sustain anti-oxidant responses and thereby support cell survival in PAH. It may become a novel treatment strategy in PAH by using of PKM2 activators.

Professionals' awareness of operational antibiotic prescribing controls in UK NHS hospitals

In recent years, there have been increasing recommendations for multidisciplinary collaboration between clinical pharmacists and medical microbiologists in an attempt to control the quality (and quantity) of antibiotic prescribing. A questionnaire addressing the utilization of antibiotic prescribing controls was sent to the chief pharmacist and medical microbiologist in UK NHS hospitals. Responses were received from both the chief pharmacist and the medical microbiologist employed in the same hospital from 83 hospitals (a 30% response rate from two independent studies). A high level of disagreement and poor awareness was identified between the interprofessional staff groups regarding the existence of antibiotic formulary (with disagreement between the two groups, or not known by one or both respondents, in 46% of the paired hospitals, N=38) and guideline documents (13%, N=11), performance of antibiotic prescribing audits (40%, N=33), and whether pharmacists (52%, N=43) and medical microbiologists (77%, N=64) monitored physician compliance with antibiotic prescribing control documents. This study has identified poor knowledge of the existence of basic antibiotic prescribing control mechanisms and the role of professional colleagues. It is suggested that there is some way to go before 'Agenda for Change' principles of flexible and collaborative roles are met. © 2004 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

Transglutaminases:nature's biological glues

Transglutaminases (Tgases) are a widely distributed group of enzymes that catalyse the post-translational modification of proteins by the formation of isopeptide bonds. This occurs either through protein cross-linking via epsilon-(gamma-glutamyl)lysine bonds or through incorporation of primary amines at selected peptide-bound glutamine residues. The cross-linked products, often of high molecular mass, are highly resistant to mechanical challenge and proteolytic degradation, and their accumulation is found in a number of tissues and processes where such properties are important, including skin, hair, blood clotting and wound healing. However, deregulation of enzyme activity generally associated with major disruptions in cellular homoeostatic mechanisms has resulted in these enzymes contributing to a number of human diseases, including chronic neurodegeneration, neoplastic diseases, autoimmune diseases, diseases involving progressive tissue fibrosis and diseases related to the epidermis of the skin. In the present review we detail the structural and regulatory features important in mammalian Tgases, with particular focus on the ubiquitous type 2 tissue enzyme. Physiological roles and substrates are discussed with a view to increasing and understanding the pathogenesis of the diseases associated with transglutaminases. Moreover the ability of these enzymes to modify proteins and act as biological glues has not gone unnoticed by the commercial sector. As a consequence, we have included some of the present and future biotechnological applications of this increasingly important group of enzymes.

Auctions with Untrustworthy Bidders

The paper analyzes auctions which are not completely enforceable. In such auctions, economic agents may fail to carry out their obligations, and parties involved cannot rely on external enforcement or control mechanisms for backing up a transaction. We propose two mechanisms that make bidders directly or indirectly reveal their trustworthiness. The first mechanism is based on discriminating bidding schedules that separate trustworthy from untrustworthy bidders. The second mechanism is a generalization of the Vickrey auction to the case of untrustworthy bidders. We prove that, if the winner is considered to have the trustworthiness of the second-highest bidder, truthfully declaring one's trustworthiness becomes a dominant strategy. We expect the proposed mechanisms to reduce the cost of trust management and to help agent designers avoid many market failures caused by lack of trust.

Access Rights Inheritance in Information Systems Controlled by Metadata

All information systems have to be protected. As the number of information objects and the number of users increase the task of information system’s protection becomes more difficult. One of the most difficult problems is access rights assignment. This paper describes the graph model of access rights inheritance. This model takes into account relations and dependences between different objects and between different users. The model can be implemented in the information systems controlled by the metadata, describing information objects and connections between them, such as the systems based on CASE-technology METAS.

The governance of online expression in a networked world:free-speech, surveillance and censorship

In recent years, we have witnessed the mushrooming of pro- democracy and protest movements not only in the Arab world, but also within Europe and the Americas. Such movements have ranged from popular upheavals, like in Tunisia and Egypt, to the organization of large- scale demonstrations against unpopular policies, as in Spain, Greece and Poland. What connects these different events are not only their democratic aspirations, but also their innovative forms of communication and organization through online means, which are sometimes considered to be outside of the State’s control. At the same time, however, it has become more and more apparent that countries are attempting to increase their understanding of, and control over, their citizens’ actions in the digital sphere. This involves striving to develop surveillance instruments, control mechanisms and processes engineered to dominate the digital public sphere, which necessitates the assistance and support of private actors such as Internet intermediaries. Examples include the growing use of Internet surveillance technology with which online data traffic is analysed, and the extensive monitoring of social networks. Despite increased media attention, academic debate on the ambivalence of these technologies, mechanisms and techniques remains relatively limited, as is discussion of the involvement of corporate actors. The purpose of this edited volume is to reflect on how Internet-related technologies, mechanisms and techniques may be used as a means to enable expression, but also to restrict speech, manipulate public debate and govern global populaces.

Potential Application of Phage Therapy Against Pseudomonas aeruginosa Biofilm Infection in Cystic Fibrosis Patients

Majority of the microbial activity in humans is in the form of biofilms i.e. an Exopolysaccharide-enclosed bacterial mass. Unlike planktonic cells and the cells on the surface of the biofilm, the biofilm-embedded cells are more resistant to the effects of the antibiotics and the host cellular defense mechanisms. A combination of biofilm growth and inherent resistance prevents effective antibiotics treatment of Pseudomonas aeruginosa infections including those in patients with cystic fibrosis. This has lead to an increasing interest in alternative modalities of treatment. Thus, phages that multiply in situ, only in the presence of susceptible hosts can be used as natural, self-limiting, and deeply penetrating antibacterial agents. The objective of this study is to identify effective phages against a collection of P. aeruginosa isolates (PCOR strains) including the prototype PAOl and the isogenic constitutively alginate-producing PD0300 strains.These PCOR strains were tested against six phages (P105, P134, P140, P168, P175B and P182). Analysis shows 69 % of the PCOR isolates are sensitive and the rest are resistant to all six phages. These phages were then tested for their ability to inhibit biofilm formation using a modified biofilm assay. The analysis demonstrated that the sensitive strains showed increased resistance but none of the sensitive strains from the initial screening were resistant. Using the minimum biofilm eradication concentration (MBEC) assay for biofilm formation, the biofilm eradication ability of the phages was tested. The data showed that a higher volume of phage was required to eradicate preformed biofilms than the volume required to prevent colonization of planktonic cells. This data supports the idea of phage therapy more as a prophylactic treatment.

Controle de mobilidade infraestruturado e orientado à qualidade para maximização de admissões em sistemas WiNeMO: uma abordagem definida por software

The spread of wireless networks and growing proliferation of mobile devices require the development of mobility control mechanisms to support the different demands of traffic in different network conditions. A major obstacle to developing this kind of technology is the complexity involved in handling all the information about the large number of Moving Objects (MO), as well as the entire signaling overhead required to manage these procedures in the network. Despite several initiatives have been proposed by the scientific community to address this issue they have not proved to be effective since they depend on the particular request of the MO that is responsible for triggering the mobility process. Moreover, they are often only guided by wireless medium statistics, such as Received Signal Strength Indicator (RSSI) of the candidate Point of Attachment (PoA). Thus, this work seeks to develop, evaluate and validate a sophisticated communication infrastructure for Wireless Networking for Moving Objects (WiNeMO) systems by making use of the flexibility provided by the Software-Defined Networking (SDN) paradigm, where network functions are easily and efficiently deployed by integrating OpenFlow and IEEE 802.21 standards. For purposes of benchmarking, the analysis was conducted in the control and data planes aspects, which demonstrate that the proposal significantly outperforms typical IPbased SDN and QoS-enabled capabilities, by allowing the network to handle the multimedia traffic with optimal Quality of Service (QoS) transport and acceptable Quality of Experience (QoE) over time.