State Transitions and the Continuum Limit for a 2D Interacting, Self-Propelled Particle System

We study a class of swarming problems wherein particles evolve dynamically via pairwise interaction potentials and a velocity selection mechanism. We find that the swarming system undergoes various changes of state as a function of the self-propulsion and interaction potential parameters. In this paper, we utilize a procedure which, in a definitive way, connects a class of individual-based models to their continuum formulations and determine criteria for the validity of the latter. H-stability of the interaction potential plays a fundamental role in determining both the validity of the continuum approximation and the nature of the aggregation state transitions. We perform a linear stability analysis of the continuum model and compare the results to the simulations of the individual-based one

A new approach for identifying non-pathogenic mutations. An analysis of the cystic fibrosis transmembrane regulator gene in normal individuals

Given q as the global frequency of the alleles causing a disease, any allele with a frequency higher than q minus the cumulative frequency of the previously known disease-causing mutations (threshold) cannot be the cause of that disease. This principle was applied to the analysis of cystic fibrosis transmembrane conductance regulator (CFTR) mutations in order to decide whether they are the cause of cystic fibrosis. A total of 191 DNA samples fl-om random individuals from Italy, France, and Spain were investigated by DGGE (denaturing gradient gel electrophoresis) analysis of all the coding and proximal non-coding regions of the gene. The mutations detected by DGGE were identified by sequencing. The sample size was sufficient to select essentially all mutations with a frequency of at least 0.01. A total of 46 mutations was detected, 20 of which were missense mutations. Four new mutations were identified: 1341+28 C/T, 2082 C/T, L1096R, and I1131V. Thirteen mutations (125 G/C, 875+40 A/G, TTGAn, IVS8-6 5T, IVS8-6 9T, 1525-61 A/G, M470V, 2693 T/G, 3061-65 C/A, 4002 A/G, 4521 G/A, IVS8 TG10, IVS8 TG12) were classified as non-CF-causing alleles on the basis of their frequency. The remaining mutations have a cumulative frequency far exceeding q; therefore, most of them cannot be CF-causing mutations. This is the first random survey capable of detecting all the polymorphisms of the coding sequence of a gene

Silence Is Not Golden: Invisible Latinas Living with HIV in the Midwest

This qualitative study was conducted to better understand the health needs and concerns of immigrant HIV-infected Latinas residing in the Midwest United States. Individual interviews (n = 18) were conducted in Spanish with Latinas in Kansas, Oklahoma and Missouri. Women were at different stages of acceptance about their HIV diagnosis and four common themes emerged from the data: pregnancy as a death sentence, HIV is taboo, God as their only resource, and living in isolation. Silence was an over-arching theme present throughout all the narratives and many women had never shared their stories about HIV with anyone. Depressive symptoms and suicidal ideation were common. These findings have implications for strategies to address the HIV prevention and HIV-related healthcare needs of this population of women. Results from this study further suggest that efforts are needed to break the silence surrounding HIV and to reduce HIV-related stigma in smaller Midwestern Hispanic communities

Voltage-gated Na⁺ channel activity increases colon cancertranscriptional activity and invasion via persistent MAPK signaling

© 2015 Macmillan Publishers Limited. All rights reserved. Functional expression of voltage-gated Na+ channels (VGSCs) has been demonstrated in multiple cancer cell types where channel activity induces invasive activity. The signaling mechanisms by which VGSCs promote oncogenesis remain poorly understood. We explored the signal transduction process critical to VGSC-mediated invasion on the basis of reports linking channel activity to gene expression changes in excitable cells. Coincidentally, many genes transcriptionally regulated by the SCN5A isoform in colon cancer have an over-representation of cis-acting sites for transcription factors phosphorylated by ERK1/2 MAPK. We hypothesized that VGSC activity promotes MAPK activation to induce transcriptional changes in invasion-related genes. Using pharmacological inhibitors/activators and siRNA-mediated gene knockdowns, we correlated channel activity with Rap1-dependent persistent MAPK activation in the SW620 human colon cancer cell line. We further demonstrated that VGSC activity induces downstream changes in invasion-related gene expression via a PKA/ERK/c-JUN/ELK-1/ETS-1 transcriptional pathway. This is the first study illustrating a molecular mechanism linking functional activity of VGSCs to transcriptional activation of invasion-related genes

Veratridine produces distinct calcium response profiles in mouse Dorsal Root Ganglia neurons.

Nociceptors are a subpopulation of dorsal root ganglia (DRG) neurons that detect noxious stimuli and signal pain. Veratridine (VTD) is a voltage-gated sodium channel (VGSC) modifier that is used as an "agonist" in functional screens for VGSC blockers. However, there is very little information on VTD response profiles in DRG neurons and how they relate to neuronal subtypes. Here we characterised VTD-induced calcium responses in cultured mouse DRG neurons. Our data shows that the heterogeneity of VTD responses reflects distinct subpopulations of sensory neurons. About 70% of DRG neurons respond to 30-100 μM VTD. We classified VTD responses into four profiles based upon their response shape. VTD response profiles differed in their frequency of occurrence and correlated with neuronal size. Furthermore, VTD response profiles correlated with responses to the algesic markers capsaicin, AITC and α, β-methylene ATP. Since VTD response profiles integrate the action of several classes of ion channels and exchangers, they could act as functional "reporters" for the constellation of ion channels/exchangers expressed in each sensory neuron. Therefore our findings are relevant to studies and screens using VTD to activate DRG neurons

N-Terminal Arginines Modulate Plasma-Membrane Localization of Kv7.1/KCNE1 Channel Complexes

BACKGROUND AND OBJECTIVE: The slow delayed rectifier current (I(Ks)) is important for cardiac action potential termination. The underlying channel is composed of Kv7.1 α-subunits and KCNE1 β-subunits. While most evidence suggests a role of KCNE1 transmembrane domain and C-terminus for the interaction, the N-terminal KCNE1 polymorphism 38G is associated with reduced I(Ks) and atrial fibrillation (a human arrhythmia). Structure-function relationship of the KCNE1 N-terminus for I(Ks) modulation is poorly understood and was subject of this study. METHODS: We studied N-terminal KCNE1 constructs disrupting structurally important positively charged amino-acids (arginines) at positions 32, 33, 36 as well as KCNE1 constructs that modify position 38 including an N-terminal truncation mutation. Experimental procedures included molecular cloning, patch-clamp recording, protein biochemistry, real-time-PCR and confocal microscopy. RESULTS: All KCNE1 constructs physically interacted with Kv7.1. I(Ks) resulting from co-expression of Kv7.1 with non-atrial fibrillation '38S' was greater than with any other construct. Ionic currents resulting from co-transfection of a KCNE1 mutant with arginine substitutions ('38G-3xA') were comparable to currents evoked from cells transfected with an N-terminally truncated KCNE1-construct ('Δ1-38'). Western-blots from plasma-membrane preparations and confocal images consistently showed a greater amount of Kv7.1 protein at the plasma-membrane in cells co-transfected with the non-atrial fibrillation KCNE1-38S than with any other construct. CONCLUSIONS: The results of our study indicate that N-terminal arginines in positions 32, 33, 36 of KCNE1 are important for reconstitution of I(Ks). Furthermore, our results hint towards a role of these N-terminal amino-acids in membrane representation of the delayed rectifier channel complex

Flash Expansion Threshold in Whirligig Swarms

<div><p>In the selfish herd hypothesis, prey animals move toward each other to avoid the likelihood of being selected by a predator. However, many grouped animals move <i>away</i> from each other the moment before a predator attacks. Very little is known about this phenomenon, called flash expansion, such as whether it is triggered by one individual or a threshold and how information is transferred between group members. We performed a controlled experiment with whirligig beetles in which the ratio of sighted to unsighted individuals was systematically varied and emergent flash expansion was measured. Specifically, we examined: the percentage of individuals in a group that startled, the resulting group area, and the longevity of the flash expansion. We found that one or two sighted beetles in a group of 24 was not enough to cause a flash expansion after a predator stimulus, but four sighted beetles usually initiated a flash expansion. Also, the more beetles that were sighted the larger the resulting group area and the longer duration of the flash expansion. We conclude that flash expansion is best described as a threshold event whose adaptive value is to prevent energetically costly false alarms while quickly mobilizing an emergent predator avoidance response. This is one of the first controlled experiments of flash expansion, an important emergent property that has applications to understanding collective motion in swarms, schools, flocks, and human crowds. Also, our study is a convincing demonstration of social contagion, how the actions of one individual can pass through a group.</p></div

Scatterplot of Sighted vs. Startled beetles: Scatterplot of actual sighted whirligigs joining a group in a population of 24 on the mean percentage of whirligigs to startle after a predator stimulus (n = 105 groups, statistics are shown in Table 1).

<p>The fitted Sumpter-Pratt equation described in the data analysis section is shown (T = 1.704, K = 1.835).</p