A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation

Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium _Escherichia coli_, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the _in vivo_ MinDE localization dynamics by accounting for the established properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally

Development and implementation of an herbal and natural product elective in undergraduate medical education

<p>Abstract</p> <p>Background</p> <p>Medical students have consistently expressed interest in learning about alternative healing modalities, especially herbal and natural products. To fill this void in medical education at our institution, a novel elective was developed and implemented for fourth year medical students. This herbal/natural product course uses guest lecturers, classroom presentations, and active learning mechanisms that include experiential rotations, case-based learning, and team-based learning to increase student knowledge of herbal/natural product safety and efficacy.</p> <p>Methods</p> <p>Knowledge outcomes were evaluated via administration of a pre- and post-course test (paired student <it>t</it>-test). End-of-course evaluations (Likert-type questions and narrative responses) were used to assess student opinion of knowledge and skills imparted by the elective and overall course content (mean, standard deviation).</p> <p>Results</p> <p>Over three academic years, 23 students have enrolled in this elective. More than 60% of participants have been female and nearly half of the students (43%) have pursued residencies in primary care. Completion of the course significantly increased student knowledge of common herbal/natural product mechanisms, uses, adverse effects, and drug-interactions as determined by a pre- and post-course knowledge assessment (45% ± 10% versus 78% ± 6%; p < 0.0001). The course was highly rated by enrollees (overall course quality, 4.6 of 5.0 ± 0.48) who appreciated the variety of activities to which they were exposed and the open classroom discussions that resulted. While students tended to view some alternative medical systems with skepticism, they still believed it was valuable to learn what these modalities encompass.</p> <p>Conclusions</p> <p>Development and implementation of a herbal/natural product elective that engages undergraduate medical students through active learning mechanisms and critical analysis of the literature has proven effective in increasing knowledge outcomes and is deemed to be a valuable curricular addition by student participants. In the future, it will be of interest to explore mechanisms for expanding the course to reach a larger number of students within the time, financial, and logistical constraints that currently exist.</p

Signalling plasticity and energy saving in a tropical bushcricket

Males of the tropical bushcricket Mecopoda elongata synchronize their acoustic advertisement signals (chirps) in interactions with other males. However, synchrony is not perfect and distinct leader and follower roles are often maintained. In entrainment experiments in which conspecific signals were presented at various rates, chirps displayed as follower showed notable signal plasticity. Follower chirps were shortened by reducing the number and duration of syllables, especially those of low and medium amplitude. The degree of shortening depended on the time delay between leader and follower signals and the sound level of the entraining stimulus. The same signal plasticity was evident in male duets, with the effect that the last syllables of highest amplitude overlapped more strongly. Respiratory measurements showed that solo singing males producing higher chirp rates suffered from higher metabolic costs compared to males singing at lower rates. In contrast, respiratory rate was rather constant during a synchronous entrainment to a conspecific signal repeated at various rates. This allowed males to maintain a steady duty cycle, associated with a constant metabolic rate. Results are discussed with respect to the preference for leader signals in females and the possible benefits males may gain by overlapping their follower signals in a chorus

Treatment Outcome in Patients Receiving Assertive Community Treatment

In an observational study of severely mentally ill patients treated in assertive community treatment (ACT) teams, we investigated how treatment outcome was associated with demographic factors, clinical factors, and motivation for treatment. To determine psychosocial outcome, patients were routinely assessed using the Health of the Nation Outcome Scales (HoNOS). Trends over time were analyzed using a mixed model with repeated measures. The HoNOS total score was modeled as a function of treatment duration and patient-dependent covariates. Data comprised 637 assessments of 139 patients; mean duration of follow-up was 27.4 months (SD = 5.4). Substance abuse, higher age, problems with motivation, and lower educational level were associated with higher HoNOS total scores (i.e., worse outcome). To improve treatment outcome, we recommend better implementation of ACT, and also the implementation of additional programs targeting subgroups which seem to benefit less from ACT

Localisation of Human Papillomavirus 16 E7 Oncoprotein Changes with Cell Confluence

E7 is one of the best studied proteins of human papillomavirus type 16, largely because of its oncogenic potential linked to cervical cancer. Yet the sub-cellular location of E7 remains confounding, even though it has been shown to be able to shuttle between the nucleus and the cytoplasm. Here we show with immunocytochemistry that E7 proteins are located in the nucleus and cytoplasm in sub-confluent cells, but becomes cytoplasmic in confluent cells. The change in E7's location is independent of time in culture, cell division, cell cycle phase or cellular differentiation. Levels of E7 are also increased in confluent cells as determined by Western blotting. Our investigations have also uncovered how different analytical techniques influence the observation of where E7 is localised, highlighting the importance of technical choice in such analysis. Understanding the localisation of E7 will help us to better comprehend the function of E7 on its target proteins

Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides

BACKGROUND: The alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) is well known as a potent calcium ionophore that, in the brain, has been implicated in excitotoxicity and hence in the underlying mechanisms of neurodegenerative disorders such as Alzheimer's disease. Previous research implied that the activity of this receptor may be modified by exposure to a peptide fragment derived from the C-terminal region of the enzyme acetylcholinesterase. This investigation was undertaken to determine if the functional changes observed could be attributed to peptide binding interaction with the alpha7-nAChR, or peptide modulation of receptor expression. METHODOLOGY/PRINCIPAL FINDINGS: This study provides evidence that two peptides derived from the C-terminus of acetylcholinesterase, not only selectively displace specific bungarotoxin binding at the alpha7-nAChR, but also alter receptor binding properties for its familiar ligands, including the alternative endogenous agonist choline. Of more long-term significance, these peptides also induce upregulation of alpha7-nAChR mRNA and protein expression, as well as enhancing receptor trafficking to the plasma membrane. CONCLUSIONS/SIGNIFICANCE: The results reported here demonstrate a hitherto unknown relationship between the alpha7-nAChR and the non-enzymatic functions of acetylcholinesterase, mediated independently by its C-terminal domain. Such an interaction may prove valuable as a pharmacological tool, prompting new approaches for understanding, and combating, the process of neurodegeneration

Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides

BACKGROUND: The alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) is well known as a potent calcium ionophore that, in the brain, has been implicated in excitotoxicity and hence in the underlying mechanisms of neurodegenerative disorders such as Alzheimer's disease. Previous research implied that the activity of this receptor may be modified by exposure to a peptide fragment derived from the C-terminal region of the enzyme acetylcholinesterase. This investigation was undertaken to determine if the functional changes observed could be attributed to peptide binding interaction with the alpha7-nAChR, or peptide modulation of receptor expression. METHODOLOGY/PRINCIPAL FINDINGS: This study provides evidence that two peptides derived from the C-terminus of acetylcholinesterase, not only selectively displace specific bungarotoxin binding at the alpha7-nAChR, but also alter receptor binding properties for its familiar ligands, including the alternative endogenous agonist choline. Of more long-term significance, these peptides also induce upregulation of alpha7-nAChR mRNA and protein expression, as well as enhancing receptor trafficking to the plasma membrane. CONCLUSIONS/SIGNIFICANCE: The results reported here demonstrate a hitherto unknown relationship between the alpha7-nAChR and the non-enzymatic functions of acetylcholinesterase, mediated independently by its C-terminal domain. Such an interaction may prove valuable as a pharmacological tool, prompting new approaches for understanding, and combating, the process of neurodegeneration

The crossroads of evidence-based medicine and health policy: implications for urology

As healthcare spending in the United States continues to rise at an unsustainable rate, recent policy decisions introduced at the national level will rely on precepts of evidence-based medicine to promote the determination, dissemination, and delivery of “best practices” or quality care while simultaneously reducing cost. We discuss the influence of evidence-based medicine on policy and, in turn, the impact of policy on the developing clinical evidence base with an eye to the potential effects of these relationships on the practice and provision of urologic care

The relationship between literacy and multimorbidity in a primary care setting

<p>Abstract</p> <p>Background</p> <p>Multimorbidity is now acknowledged as a research priority in primary care. The identification of risk factors and people most at risk is an important step in guiding prevention and intervention strategies. The aim of this study was to examine the relationship between literacy and multimorbidity while controlling for potential confounders.</p> <p>Methods</p> <p>Participants were adult patients attending the family medicine clinic of a regional health centre in Saguenay (Quebec), Canada. Literacy was measured with the Newest Vital Sign (NVS). Multimorbidity was measured with the Disease Burden Morbidity Assessment (DBMA) by self-report. Information on potential confounders (age, sex, education and family income) was also collected. The association between literacy (independent variable) and multimorbidity was examined in bivariate and multivariate analyses. Two operational definitions of multimorbidity were used successively as the dependent variable; confounding variables were introduced into the model as potential predictors.</p> <p>Results</p> <p>One hundred three patients (36 men) 19–83 years old were recruited; 41.8% had completed 12 years of school or less. Forty-seven percent of patients provided fewer than four correct answers on the NVS (possible low literacy) whereas 53% had four correct responses or more. Literacy and multimorbidity were associated in bivariate analyses (p < 0.01) but not in multivariate analyses, including age and family income.</p> <p>Conclusion</p> <p>This study suggests that there is no relationship between literacy and multimorbidity when controlling for age and family income.</p