Telomeres cluster de novo before the initiation of synapsis: a three-dimensional spatial analysis of telomere positions before and during meiotic prophase.

We have analyzed the progressive changes in the spatial distribution of telomeres during meiosis using three-dimensional, high resolution fluorescence microscopy. Fixed meiotic cells of maize (Zea mays L.) were subjected to in situ hybridization under conditions that preserved chromosome structure, allowing identification of stage-dependent changes in telomere arrangements. We found that nuclei at the last somatic prophase before meiosis exhibit a nonrandom, polarized chromosome organization resulting in a loose grouping of telomeres. Quantitative measurements on the spatial arrangements of telomeres revealed that, as cells passed through premeiotic interphase and into leptotene, there was an increase in the frequency of large telomere-to-telomere distances and a decrease in the bias toward peripheral localization of telomeres. By leptotene, there was no obvious evidence of telomere grouping, and the large, singular nucleolus was internally located, nearly concentric with the nucleus. At the end of leptotene, telomeres clustered de novo at the nuclear periphery, coincident with a displacement of the nucleolus to one side. The telomere cluster persisted throughout zygotene and into early pachytene. The nucleolus was adjacent to the cluster at zygotene. At the pachytene stage, telomeres rearranged again by dispersing throughout the nuclear periphery. The stage-dependent changes in telomere arrangements are suggestive of specific, active telomere-associated motility processes with meiotic functions. Thus, the formation of the cluster itself is an early event in the nuclear reorganizations associated with meiosis and may reflect a control point in the initiation of synapsis or crossing over

A comparative framework: how broadly applicable is a 'rigorous' critical junctures framework?

The paper tests Hogan and Doyle's (2007, 2008) framework for examining critical junctures. This framework sought to incorporate the concept of ideational change in understanding critical junctures. Until its development, frameworks utilized in identifying critical junctures were subjective, seeking only to identify crisis, and subsequent policy changes, arguing that one invariably led to the other, as both occurred around the same time. Hogan and Doyle (2007, 2008) hypothesized ideational change as an intermediating variable in their framework, determining if, and when, a crisis leads to radical policy change. Here we test this framework on cases similar to, but different from, those employed in developing the exemplar. This will enable us determine whether the framework's relegation of ideational change to a condition of crisis holds, or, if ideational change has more importance than is ascribed to it by this framework. This will also enable us determined if the framework itself is robust, and fit for the purposes it was designed to perform — identifying the nature of policy change

Increasing the satisfaction of general practitioners with continuing medical education programs: A method for quality improvement through increasing teacher-learner interaction

BACKGROUND: Continuing medical education (CME) for general practitioners relies on specialist-based teaching methods in many settings. Formal lectures by specialists may not meet the learning needs of practitioners and may cause dissatisfaction with traditional CME. Increasing learner involvement in teaching programs may improve learner satisfaction. METHODS: A quality improvement program for CME for 18 general practitioners in the Tel Aviv region was designed as a result of dissatisfaction with traditional CME activities. A two-step strategy for change was developed. The CME participants first selected the study topics relevant to them from a needs assessment and prepared background material on the topics. In the second step, specialist teachers were invited to answer questions arising from the preparation of selected topics. Satisfaction with the traditional lecture program and the new participatory program were assessed by a questionnaire. The quality criteria included the relevance, importance and applicability of the CME topic chosen to the participant's practice, the clarity of the presentation and the effective use of teaching aids by the lecturer and the potential of the lecturer to serve as a consultant to the participant. RESULTS: The participatory model of CME significantly increased satisfaction with relevance, applicability and interest in CME topics compared to the traditional lecture format. CONCLUSIONS: Increased learner participation in the selection and preparation of CME topics, and increased interaction between CME teachers and learners results in increased satisfaction with teaching programs. Future study of the effect of this model on physician performance is required

Causes of industrial protein a column degradation, explored using Raman spectroscopy.

Monoclonal antibodies (mAbs) are used extensively as biotherapeutics for chronic and acute conditions. Production of mAbs is lengthy and expensive, with protein A affinity capture the most costly step, due both to the nature of the resin and its marked reduction in binding capacity with repeated use. Our previous studies using in situ ATR-FTIR spectroscopy indicated that loss in protein A binding capacity is not the result of leaching or degradation of protein A ligand, suggesting fouling is the principal cause. Here we explore binding behavior and resin capacity loss using Raman spectroscopy. Our data reveal a distinct Raman spectral fingerprint for mAb bound to the protein A ligand of MabSelect SuRe. The results show that the drop in static binding capacity (SBC) previously observed for used protein A resin is discernible by Raman spectroscopy in combination with partial least-squares regression. The SBC is lowest (35.76 mg mL-1) for used inlet resin compared to used outlet (40.17 mg mL-1) and unused resin samples (70.35 mg mL-1). Depth profiling by Raman spectroscopy indicates that at below saturating concentrations (∼18 mg mL-1), binding of mAb is not homogeneous through used resin beads with protein binding preferentially to the outer regions of the bead, in contrast to fully homogeneous distribution through unused control MabSelect SuRe resin beads. Analysis of the Raman spectra indicates that one foulant is irreversibly bound mAb. The presence of irreversibly bound mAb and host cell proteins was confirmed by mass spectrometric analysis of used resin beads

When the optimal is not the best: parameter estimation in complex biological models

Background: The vast computational resources that became available during the past decade enabled the development and simulation of increasingly complex mathematical models of cancer growth. These models typically involve many free parameters whose determination is a substantial obstacle to model development. Direct measurement of biochemical parameters in vivo is often difficult and sometimes impracticable, while fitting them under data-poor conditions may result in biologically implausible values. Results: We discuss different methodological approaches to estimate parameters in complex biological models. We make use of the high computational power of the Blue Gene technology to perform an extensive study of the parameter space in a model of avascular tumor growth. We explicitly show that the landscape of the cost function used to optimize the model to the data has a very rugged surface in parameter space. This cost function has many local minima with unrealistic solutions, including the global minimum corresponding to the best fit. Conclusions: The case studied in this paper shows one example in which model parameters that optimally fit the data are not necessarily the best ones from a biological point of view. To avoid force-fitting a model to a dataset, we propose that the best model parameters should be found by choosing, among suboptimal parameters, those that match criteria other than the ones used to fit the model. We also conclude that the model, data and optimization approach form a new complex system, and point to the need of a theory that addresses this problem more generally

Decreasing intensity of open-ocean convection in the Greenland and Iceland seas

The air–sea transfer of heat and fresh water plays a critical role in the global climate system. This is particularly true for the Greenland and Iceland seas, where these fluxes drive ocean convection that contributes to Denmark Strait overflow water, the densest component of the lower limb of the Atlantic Meridional Overturning Circulation (AMOC). Here we show that the wintertime retreat of sea ice in the region, combined with different rates of warming for the atmosphere and sea surface of the Greenland and Iceland seas, has resulted in statistically significant reductions of approximately 20% in the magnitude of the winter air–sea heat fluxes since 1979. We also show that modes of climate variability other than the North Atlantic Oscillation (NAO) are required to fully characterize the regional air–sea interaction. Mixed-layer model simulations imply that further decreases in atmospheric forcing will exceed a threshold for the Greenland Sea whereby convection will become depth limited, reducing the ventilation of mid-depth waters in the Nordic seas. In the Iceland Sea, further reductions have the potential to decrease the supply of the densest overflow waters to the AMOC

Thermoelastic properties of magnesiowustite, (Mg1-xFex)O: determination of the Anderson-Gruneisen parameter by time-of-flight neutron powder diffraction at simultaneous high pressures and temperatures

The ability to perform neutron diffraction studies at simultaneous high pressures and high temperatures is a relatively recent development. The suitability of this technique for determining P-V-T equations of state has been investigated by measuring the lattice parameters of Mg1-xFexO ( x = 0.2, 0.3, 0.4), in the range P < 10.3 GPa and 300 < T < 986 K, by time-of-flight neutron powder diffraction. Pressures were determined using metallic Fe as a marker and temperatures were measured by neutron absorption resonance radiography. Within the resolution of the experiment, no evidence was found for any change in the temperature derivative of the isothermal incompressibility, partial derivative K-T/partial derivative T, with composition. By assuming that the equation-of-state parameters either varied linearly or were invariant with composition, the 60 measured state points were fitted simultaneously to a P-V-T-x equation of state, leading to values of partial derivative K-T/partial derivative T = -0.024 (9) GPa K-1 and of the isothermal Anderson-Gruneisen parameter delta(T) = 4.0 (16) at 300 K. Two designs of simultaneous high-P/T cell were employed during this study. It appears that, by virtue of its extended pressure range, a design using toroidal gaskets is more suitable for equation-of-state studies than is the system described by Le Godec, Dove, Francis, Kohn, Marshall, Pawley, Price, Redfern, Rhodes, Ross, Schofield, Schooneveld, Syfosse, Tucker & Welch [Mineral. Mag. (2001), 65, 737-748]. (c) 2008 International Union of Crystallography Printed in Singapore - all rights reserved

MRSA model of learning and adaptation: a qualitative study among the general public

<p>Abstract</p> <p>Background</p> <p>More people in the US now die from Methicillin Resistant <it>Staphylococcus aureus </it>(MRSA) infections than from HIV/AIDS. Often acquired in healthcare facilities or during healthcare procedures, the extremely high incidence of MRSA infections and the dangerously low levels of literacy regarding antibiotic resistance in the general public are on a collision course. Traditional medical approaches to infection control and the conventional attitude healthcare practitioners adopt toward public education are no longer adequate to avoid this collision. This study helps us understand how people acquire and process new information and then adapt behaviours based on learning.</p> <p>Methods</p> <p>Using constructivist theory, semi-structured face-to-face and phone interviews were conducted to gather pertinent data. This allowed participants to tell their stories so their experiences could deepen our understanding of this crucial health issue. Interview transcripts were analysed using grounded theory and sensitizing concepts.</p> <p>Results</p> <p>Our findings were classified into two main categories, each of which in turn included three subthemes. First, in the category of <it>Learning</it>, we identified how individuals used their <it>Experiences with MRSA</it>, to answer the questions: <it>What was learned? </it>and, <it>How did learning occur? </it>The second category, <it>Adaptation </it>gave us insights into <it>Self-reliance, Reliance on others</it>, and <it>Reflections on the MRSA journey</it>.</p> <p>Conclusions</p> <p>This study underscores the critical importance of educational programs for patients, and improved continuing education for healthcare providers. Five specific results of this study can reduce the vacuum that currently exists between the knowledge and information available to healthcare professionals, and how that information is conveyed to the public. These points include: 1) a common model of MRSA learning and adaptation; 2) the self-directed nature of adult learning; 3) the focus on general MRSA information, care and prevention, and antibiotic resistance; 4) the interconnected nature of adaptation; and, 5) the need for a consistent step by step plan to deal with MRSA provided at the time of diagnosis.</p