In vitro synthesis of heparosan using recombinant Pasteurella multocida heparosan synthase PmHS2

In vertebrates and bacteria, heparosan the precursor of heparin is synthesized by glycosyltransferases via the stepwise addition of UDP-N-acetylglucosamine and UDP-glucuronic acid. As heparin-like molecules represent a great interest in the pharmaceutical area, the cryptic Pasteurella multocida heparosan synthase PmHS2 found to catalyze heparosan synthesis using substrate analogs has been studied. In this paper, we report an efficient way to purify PmHS2 and to maintain its activity stable during 6 months storage at −80 °C using His-tag purification and a desalting step. In the presence of 1 mM of each nucleotide sugar, purified PmHS2 synthesized polymers up to an average molecular weight of 130 kDa. With 5 mM of UDP-GlcUA and 5 mM of UDP-GlcNAc, an optimal specific activity, from 3 to 6 h of incubation, was found to be about 0.145 nmol/μg/min, and polymers up to an average of 102 kDa were synthesized in 24 h. In this study, we show that the chain length distribution of heparosan polymers can be controlled by change of the initial nucleotide sugar concentration. It was observed that low substrate concentration favors the formation of high molecular weight heparosan polymer with a low polydispersity while high substrate concentration did the opposite. Similarities in the polymerization mechanism between PmHS2, PmHS1, and PmHAS are discussed

Stochastic population growth in spatially heterogeneous environments

Classical ecological theory predicts that environmental stochasticity increases extinction risk by reducing the average per-capita growth rate of populations. To understand the interactive effects of environmental stochasticity, spatial heterogeneity, and dispersal on population growth, we study the following model for population abundances in $n$ patches: the conditional law of $X_{t+dt}$ given $X_t=x$ is such that when $dt$ is small the conditional mean of $X_{t+dt}^i-X_t^i$ is approximately $[x^i\mu_i+\sum_j(x^j D_{ji}-x^i D_{ij})]dt$, where $X_t^i$ and $\mu_i$ are the abundance and per capita growth rate in the $i$-th patch respectivly, and $D_{ij}$ is the dispersal rate from the $i$-th to the $j$-th patch, and the conditional covariance of $X_{t+dt}^i-X_t^i$ and $X_{t+dt}^j-X_t^j$ is approximately $x^i x^j \sigma_{ij}dt$. We show for such a spatially extended population that if $S_t=(X_t^1+...+X_t^n)$ is the total population abundance, then $Y_t=X_t/S_t$, the vector of patch proportions, converges in law to a random vector $Y_\infty$ as $t\to\infty$, and the stochastic growth rate $\lim_{t\to\infty}t^{-1}\log S_t$ equals the space-time average per-capita growth rate \sum_i\mu_i\E[Y_\infty^i] experienced by the population minus half of the space-time average temporal variation \E[\sum_{i,j}\sigma_{ij}Y_\infty^i Y_\infty^j] experienced by the population. We derive analytic results for the law of $Y_\infty$, find which choice of the dispersal mechanism $D$ produces an optimal stochastic growth rate for a freely dispersing population, and investigate the effect on the stochastic growth rate of constraints on dispersal rates. Our results provide fundamental insights into "ideal free" movement in the face of uncertainty, the persistence of coupled sink populations, the evolution of dispersal rates, and the single large or several small (SLOSS) debate in conservation biology.Comment: 47 pages, 4 figure

How predation and landscape fragmentation affect vole population dynamics

Background: Microtine species in Fennoscandia display a distinct north-south gradient from regular cycles to stable populations. The gradient has often been attributed to changes in the interactions between microtines and their predators. Although the spatial structure of the environment is known to influence predator-prey dynamics of a wide range of species, it has scarcely been considered in relation to the Fennoscandian gradient. Furthermore, the length of microtine breeding season also displays a north-south gradient. However, little consideration has been given to its role in shaping or generating population cycles. Because these factors covary along the gradient it is difficult to distinguish their effects experimentally in the field. The distinction is here attempted using realistic agent-based modelling. Methodology/Principal Findings: By using a spatially explicit computer simulation model based on behavioural and ecological data from the field vole (Microtus agrestis), we generated a number of repeated time series of vole densities whose mean population size and amplitude were measured. Subsequently, these time series were subjected to statistical autoregressive modelling, to investigate the effects on vole population dynamics of making predators more specialised, of altering the breeding season, and increasing the level of habitat fragmentation. We found that fragmentation as well as the presence of specialist predators are necessary for the occurrence of population cycles. Habitat fragmentation and predator assembly jointly determined cycle length and amplitude. Length of vole breeding season had little impact on the oscillations. Significance: There is good agreement between our results and the experimental work from Fennoscandia, but our results allow distinction of causation that is hard to unravel in field experiments. We hope our results will help understand the reasons for cycle gradients observed in other areas. Our results clearly demonstrate the importance of landscape fragmentation for population cycling and we recommend that the degree of fragmentation be more fully considered in future analyses of vole dynamics

Observational measure of implementation progress in community based settings: The Stages of implementation completion (SIC)

<p>Abstract</p> <p>Background</p> <p>An increasingly large body of research is focused on designing and testing strategies to improve knowledge about how to embed evidence-based programs (EBP) into community settings. Development of strategies for overcoming barriers and increasing the effectiveness and pace of implementation is a high priority. Yet, there are few research tools that measure the implementation process itself. The Stages of Implementation Completion (SIC) is an observation-based measure that is used to track the time to achievement of key implementation milestones in an EBP being implemented in 51 counties in 53 sites (two counties have two sites) in two states in the United States.</p> <p>Methods</p> <p>The SIC was developed in the context of a randomized trial comparing the effectiveness of two implementation strategies: community development teams (experimental condition) and individualized implementation (control condition). Fifty-one counties were randomized to experimental or control conditions for implementation of multidimensional treatment foster care (MTFC), an alternative to group/residential care placement for children and adolescents. Progress through eight implementation stages was tracked by noting dates of completion of specific activities in each stage. Activities were tailored to the strategies for implementing the specific EBP.</p> <p>Results</p> <p>Preliminary data showed that several counties ceased progress during pre-implementation and that there was a high degree of variability among sites in the duration scores per stage and on the proportion of activities that were completed in each stage. Progress through activities and stages for three example counties is shown.</p> <p>Conclusions</p> <p>By assessing the attainment time of each stage and the proportion of activities completed, the SIC measure can be used to track and compare the effectiveness of various implementation strategies. Data from the SIC will provide sites with relevant information on the time and resources needed to implement MTFC during various phases of implementation. With some modifications, the SIC could be appropriate for use in evaluating implementation strategies in head-to-head randomized implementation trials and as a monitoring tool for rolling out other EBPs.</p

A Multi-Stage Model for Fundamental Functional Properties in Primary Visual Cortex

Many neurons in mammalian primary visual cortex have properties such as sharp tuning for contour orientation, strong selectivity for motion direction, and insensitivity to stimulus polarity, that are not shared with their sub-cortical counterparts. Successful models have been developed for a number of these properties but in one case, direction selectivity, there is no consensus about underlying mechanisms. We here define a model that accounts for many of the empirical observations concerning direction selectivity. The model describes a single column of cat primary visual cortex and comprises a series of processing stages. Each neuron in the first cortical stage receives input from a small number of on-centre and off-centre relay cells in the lateral geniculate nucleus. Consistent with recent physiological evidence, the off-centre inputs to cortex precede the on-centre inputs by a small (∼4 ms) interval, and it is this difference that confers direction selectivity on model neurons. We show that the resulting model successfully matches the following empirical data: the proportion of cells that are direction selective; tilted spatiotemporal receptive fields; phase advance in the response to a stationary contrast-reversing grating stepped across the receptive field. The model also accounts for several other fundamental properties. Receptive fields have elongated subregions, orientation selectivity is strong, and the distribution of orientation tuning bandwidth across neurons is similar to that seen in the laboratory. Finally, neurons in the first stage have properties corresponding to simple cells, and more complex-like cells emerge in later stages. The results therefore show that a simple feed-forward model can account for a number of the fundamental properties of primary visual cortex

Demographic Diversity and Sustainable Fisheries

Fish species are diverse. For example, some exhibit early maturation while others delay maturation, some adopt semelparous reproductive strategies while others are iteroparous, and some are long-lived and others short-lived. The diversity is likely to have profound effects on fish population dynamics, which in turn has implications for fisheries management. In this study, a simple density-dependent stage-structured population model was used to investigate the effect of life history traits on sustainable yield, population resilience, and the coefficient of variation (CV) of the adult abundance. The study showed that semelparous fish can produce very high sustainable yields, near or above 50% of the carrying capacity, whereas long-lived iteroparous fish can produce very low sustainable yields, which are often much less than 10% of the carrying capacity. The difference is not because of different levels of sustainable fishing mortality rate, but because of difference in the sensitivity of the equilibrium abundance to fishing mortality. On the other hand, the resilience of fish stocks increases from delayed maturation to early maturation strategies but remains almost unchanged from semelparous to long-lived iteroparous. The CV of the adult abundance increases with increased fishing mortality, not because more individuals are recruited into the adult stage (as previous speculated), but because the mean abundance is more sensitive to fishing mortality than its standard deviation. The magnitudes of these effects vary depending on the life history strategies of the fish species involved. It is evident that any past high yield of long-lived iteroparous fish is a transient yield level, and future commercial fisheries should focus more on fish that are short-lived (including semelparous species) with high compensatory capacity

More mentoring needed? A cross-sectional study of mentoring programs for medical students in Germany

<p>Abstract</p> <p>Background</p> <p>Despite increasing recognition that mentoring is essential early in medical careers, little is known about the prevalence of mentoring programs for medical students. We conducted this study to survey all medical schools in Germany regarding the prevalence of mentoring programs for medical students as well as the characteristics, goals and effectiveness of these programs.</p> <p>Methods</p> <p>A definition of mentoring was established and program inclusion criteria were determined based on a review of the literature. The literature defined mentoring as a steady, long-lasting relationship designed to promote the mentee's overall development. We developed a questionnaire to assess key characteristics of mentoring programs: the advocated mentoring model, the number of participating mentees and mentors, funding and staff, and characteristics of mentees and mentors (e.g., level of training). In addition, the survey characterized the mentee-mentor relationship regarding the frequency of meetings, forms of communication, incentives for mentors, the mode of matching mentors and mentees, and results of program evaluations. Furthermore, participants were asked to characterize the aims of their programs. The questionnaire consisted of 34 questions total, in multiple-choice (17), numeric (7) and free-text (10) format. This questionnaire was sent to deans and medical education faculty in Germany between June and September 2009. For numeric answers, mean, median, and standard deviation were determined. For free-text items, responses were coded into categories using qualitative free text analysis.</p> <p>Results</p> <p>We received responses from all 36 medical schools in Germany. We found that 20 out of 36 medical schools in Germany offer 22 active mentoring programs with a median of 125 and a total of 5,843 medical students (6.9 - 7.4% of all German medical students) enrolled as mentees at the time of the survey. 14 out of 22 programs (63%) have been established within the last 2 years. Six programs (27%) offer mentoring in a one-on-one setting. 18 programs (82%) feature faculty physicians as mentors. Nine programs (41%) involve students as mentors in a peer-mentoring setting. The most commonly reported goals of the mentoring programs include: establishing the mentee's professional network (13 programs, 59%), enhancement of academic performance (11 programs, 50%) and counseling students in difficulties (10 programs, 45%).</p> <p>Conclusions</p> <p>Despite a clear upsurge of mentoring programs for German medical students over recent years, the overall availability of mentoring is still limited. The mentoring models and goals of the existing programs vary considerably. Outcome data from controlled studies are needed to compare the efficiency and effectiveness of different forms of mentoring for medical students.</p

Efficient Sparse Coding in Early Sensory Processing: Lessons from Signal Recovery

Sensory representations are not only sparse, but often overcomplete: coding units significantly outnumber the input units. For models of neural coding this overcompleteness poses a computational challenge for shaping the signal processing channels as well as for using the large and sparse representations in an efficient way. We argue that higher level overcompleteness becomes computationally tractable by imposing sparsity on synaptic activity and we also show that such structural sparsity can be facilitated by statistics based decomposition of the stimuli into typical and atypical parts prior to sparse coding. Typical parts represent large-scale correlations, thus they can be significantly compressed. Atypical parts, on the other hand, represent local features and are the subjects of actual sparse coding. When applied on natural images, our decomposition based sparse coding model can efficiently form overcomplete codes and both center-surround and oriented filters are obtained similar to those observed in the retina and the primary visual cortex, respectively. Therefore we hypothesize that the proposed computational architecture can be seen as a coherent functional model of the first stages of sensory coding in early vision