Dynamics of Sparsely Connected Networks of Excitatory and Inhibitory Spiking Neurons

The dynamics of networks of sparsely connected excitatory and inhibitory integrate-and-fire neurons are studied analytically. The analysis reveals a rich repertoire of states, including synchronous states in which neurons fire regularly; asynchronous states with stationary global activity and very irregular individual cell activity; and states in which the global activity oscillates but individual cells fire irregularly, typically at rates lower than the global oscillation frequency. The network can switch between these states, provided the external frequency, or the balance between excitation and inhibition, is varied. Two types of network oscillations are observed. In the fast oscillatory state, the network frequency is almost fully controlled by the synaptic time scale. In the slow oscillatory state, the network frequency depends mostly on the membrane time constant. Finite size effects in the asynchronous state are also discussed.     

Recovery of Dynamics and Function in Spiking Neural Networks with Closed-Loop Control

There is a growing interest in developing novel brain stimulation methods to control disease-related aberrant neural activity and to address basic neuroscience questions. Conventional methods for manipulating brain activity rely on open-loop approaches that usually lead to excessive stimulation and, crucially, do not restore the original computations performed by the network. Thus, they are often accompanied by undesired side-effects. Here, we introduce delayed feedback control (DFC), a conceptually simple but effective method, to control pathological oscillations in spiking neural networks (SNNs). Using mathematical analysis and numerical simulations we show that DFC can restore a wide range of aberrant network dynamics either by suppressing or enhancing synchronous irregular activity. Importantly, DFC, besides steering the system back to a healthy state, also recovers the computations performed by the underlying network. Finally, using our theory we identify the role of single neuron and synapse properties in determining the stability of the closed-loop system.     

Posture Affects How Robots and Infants Map Words to Objects

For infants, the first problem in learning a word is to map the word to its referent; a second problem is to remember that mapping when the word and/or referent are again encountered. Recent infant studies suggest that spatial location plays a key role in how infants solve both problems. Here we provide a new theoretical model and new empirical evidence on how the body – and its momentary posture – may be central to these processes. The present study uses a name-object mapping task in which names are either encountered in the absence of their target (experiments 1–3, 6 & 7), or when their target is present but in a location previously associated with a foil (experiments 4, 5, 8 & 9). A humanoid robot model (experiments 1–5) is used to instantiate and test the hypothesis that body-centric spatial location, and thus the bodies’ momentary posture, is used to centrally bind the multimodal features of heard names and visual objects. The robot model is shown to replicate existing infant data and then to generate novel predictions, which are tested in new infant studies (experiments 6–9). Despite spatial location being task-irrelevant in this second set of experiments, infants use body-centric spatial contingency over temporal contingency to map the name to object. Both infants and the robot remember the name-object mapping even in new spatial locations. However, the robot model shows how this memory can emerge –not from separating bodily information from the word-object mapping as proposed in previous models of the role of space in word-object mapping – but through the body’s momentary disposition in space.     

Orientation Selectivity in Inhibition-Dominated Networks of Spiking Neurons: Effect of Single Neuron Properties and Network Dynamics

The neuronal mechanisms underlying the emergence of orientation selectivity in the primary visual cortex of mammals are still elusive. In rodents, visual neurons show highly selective responses to oriented stimuli, but neighboring neurons do not necessarily have similar preferences. Instead of a smooth map, one observes a salt-and-pepper organization of orientation selectivity. Modeling studies have recently confirmed that balanced random networks are indeed capable of amplifying weakly tuned inputs and generating highly selective output responses, even in absence of feature-selective recurrent connectivity. Here we seek to elucidate the neuronal mechanisms underlying this phenomenon by resorting to networks of integrate-and-fire neurons, which are amenable to analytic treatment. Specifically, in networks of perfect integrate-and-fire neurons, we observe that highly selective and contrast invariant output responses emerge, very similar to networks of leaky integrate-and-fire neurons. We then demonstrate that a theory based on mean firing rates and the detailed network topology predicts the output responses, and explains the mechanisms underlying the suppression of the common-mode, amplification of modulation, and contrast invariance. Increasing inhibition dominance in our networks makes the rectifying nonlinearity more prominent, which in turn adds some distortions to the otherwise essentially linear prediction. An extension of the linear theory can account for all the distortions, enabling us to compute the exact shape of every individual tuning curve in our networks. We show that this simple form of nonlinearity adds two important properties to orientation selectivity in the network, namely sharpening of tuning curves and extra suppression of the modulation. The theory can be further extended to account for the nonlinearity of the leaky model by replacing the rectifier by the appropriate smooth input-output transfer function. These results are robust and do not depend on the state of network dynamics, and hold equally well for mean-driven and fluctuation-driven regimes of activity.     

Dynamics of HIV-Containing Compartments in Macrophages Reveal Sequestration of Virions and Transient Surface Connections

During HIV pathogenesis, infected macrophages behave as “viral reservoirs” that accumulate and retain virions within dedicated internal Virus-Containing Compartments (VCCs). The nature of VCCs remains ill characterized and controversial. Using wild-type HIV-1 and a replication-competent HIV-1 carrying GFP internal to the Gag precursor, we analyzed the biogenesis and evolution of VCCs in primary human macrophages. VCCs appear roughly 14 hours after viral protein synthesis is detected, initially contain few motile viral particles, and then mature to fill up with virions that become packed and immobile. The amount of intracellular Gag, the proportion of dense VCCs, and the density of viral particles in their lumen increased with time post-infection. In contrast, the secretion of virions, their infectivity and their transmission to T cells decreased overtime, suggesting that HIV-infected macrophages tend to pack and retain newly formed virions into dense compartments. A minor proportion of VCCs remains connected to the plasma membrane overtime. Surprisingly, live cell imaging combined with correlative light and electron microscopy revealed that such connections can be transient, highlighting their dynamic nature. Together, our results shed light on the late phases of the HIV-1 cycle and reveal some of its macrophage specific features.     

The Genome of Thermosipho africanus TCF52B: Lateral Genetic Connections to the Firmicutes and Archaea

Lateral gene transfers (LGT) (also called horizontal gene transfers) have been a major force shaping the Thermosipho africanus TCF52B genome, whose sequence we describe here. Firmicutes emerge as the principal LGT partner. Twenty-six percent of phylogenetic trees suggest LGT with this group, while 13% of the open reading frames indicate LGT with Archaea.Thermosipho africanus TCF52B was isolated from produced fluids of a high-temperature oil reservoir in the North Sea using fish waste as the only substrate (4). Phylogenetic analyses based on the 16S rRNA gene sequence and DNA-DNA hybridization placed it as a strain of Thermosipho africanus, which was first isolated from a shallow marine hydrothermal system in Djibouti, Africa (8, 21).The complete genome sequence of this strain was determined by the conventional whole-genome shotgun strategy. Genomic libraries containing 1- to 4-kb and 40-kb fragments were constructed, and sequence chromatograms were produced using a MegaBACE 1000 capillary DNA sequencer (GE Healthcare). Nucleotide skews were computed as described previously (11). Automated open reading frame (ORF) identification and annotation were performed using the annotation software Manatee made available by TIGR (23). Pseudogenes were identified by doing BLAST searches of neighboring ORFs with the same or similar annotations and by using the program Psi-phi (9, 10), and clustered regularly interspaced short palindromic repeat loci (CRISPRs) were identified using the web site http://crispr.u-psud.fr/crispr/CRISPRHomePage.php with the default parameters (6). Maximum-likelihood (ML) trees (WAG [Γ+Ι model, four categories]) were constructed from protein-coding ORFs using PHYML and the PhyloGenie package (5). Recently, several Thermotogales genomes have become available in GenBank. As these genomes had not been published yet, we did not include them in any “genome-scale” analyses (i.e., the phylogenetic analyses). We did, however, include them in the BLAST analyses of mobile Thermosipho africanus genes.The genome of Thermosipho africanus strain TCF52B is a single circular chromosome consisting of 2,016,657 bp with an average G+C content of 30.8%. Strand asymmetries, such as GC skew and tetramer skews, are pronounced and show two clear singularity points, located at roughly 8 kb and 1033 kb from the +1 site (see Fig. S1 in the supplemental material). Since these two points are diametrically opposed on the circular chromosome, dividing it into two halves with opposite compositional skews, they make good candidates for the putative origin and termination of replication. The 1,033-kb region is likely to harbor the origin, since GC skew becomes positive past this location, as in most bacterial genomes with a known origin.The genome contains 2,000 potential coding sequences, of which 1913 are putative protein-coding ORFs, 30 are putatively assigned as pseudogenes, and 57 encode RNA. A comparison to the genome of Thermotoga maritima is given in Table ​Table1.1. The Thermosipho africanus genome is about 156 kb larger than the Thermotoga maritima genome and carries 36 more ORFs. The genome contains duplicated regions comprising paralogous gene copies, CRISPRs, and mobile genetic elements, which collectively provide considerable indirect evidence for genomic instability and acquisition of exogenous genetic information.

TABLE 1.

General features of the Thermosipho africanus genome, with a comparison to Thermotoga maritima

The Drosophila Planar Polarity Proteins Inturned and Multiple Wing Hairs Interact Physically and Function Together

The conserved frizzled (fz) pathway regulates planar cell polarity in both vertebrate and invertebrate animals. This pathway has been most intensively studied in the wing of Drosophila, where the proteins encoded by pathway genes all accumulate asymmetrically. Upstream members of the pathway accumulate on the proximal, distal, or both cell edges in the vicinity of the adherens junction. More downstream components including Inturned and Multiple Wing Hairs accumulate on the proximal side of wing cells prior to hair initiation. The Mwh protein differs from other members of the pathway in also accumulating in growing hairs. Here we show that the two Mwh accumulation patterns are under different genetic control with the early proximal accumulation being regulated by the fz pathway and the latter hair accumulation being largely independent of the pathway. We also establish recruitment by proximally localized Inturned to be a putative mechanism for the localization of Mwh to the proximal side of wing cells. Genetically inturned (in) acts upstream of mwh (mwh) and is required for the proximal localization of Mwh. We show that Mwh can bind to and co-immunoprecipitate with Inturned. We also show that these two proteins can function in close juxtaposition in vivo. An In∷Mwh fusion protein provided complete rescue activity for both in and mwh mutations. The fusion protein localized to the proximal side of wing cells prior to hair formation and in growing hairs as expected if protein localization is a key for the function of these proteins.THE frizzled (fz) signaling pathway regulates tissue planar cell polarity (PCP) in the epidermis of both vertebrate and invertebrate animals (Lawrence et al. 2007; Montcouquiol 2007; Wang and Nathans 2007; Zallen 2007). PCP is dramatic in the cuticle of insects such as Drosophila, which is decorated with arrays of hairs and sensory bristles.The genetic basis for tissue polarity has been most extensively studied in the fly wing (Wong and Adler 1993). The Planar Polarity (PCP) genes of the fz pathway (also known as the core PCP genes), the planar polarity effector (PPE) genes and the multiple wing hairs (mwh) gene encode key components that regulate planar polarity in the wing. fz, disheveled (dsh), prickle/spiny leg (pk/sple), Van Gogh (Vang) (aka strabismus), starry night (stan) (aka flamingo) and diego (dgo) are members of the PCP group (Vinson and Adler 1987; Wong and Adler 1993; Taylor et al. 1998; Wolff and Rubin 1998; Chae et al. 1999; Gubb et al. 1999; Usui et al. 1999). A distinctive feature of these genes is that their protein products accumulate asymmetrically on the distal (Fz, Dsh, and Dgo) (Axelrod 2001; Feiguin et al. 2001; Shimada et al. 2001; Strutt 2001), proximal (Vang, Pk)(Tree et al. 2002; Bastock et al. 2003), or both distal and proximal (Stan) (Usui et al. 1999) sides of wing cells. These genes/proteins act as a functional group and are corequirements for the asymmetric accumulation of the others.The PPE includes inturned (in), fuzzy (fy), and fritz (frtz) (Park et al. 1996; Collier and Gubb 1997; Collier et al. 2005). These genes are thought to function downstream of the PCP genes and the proteins encoded by these genes also accumulate asymmetrically in wing cells (Adler et al. 2004; Strutt and Warrington 2008). As is the case for the PCP genes, the PPE genes/proteins also appear to be a functional group and to be corequirements for the asymmetric accumulation of the others. Several observations support the hypothesis that the PPE genes are essential downstream effectors of the PCP genes. The earliest appreciation of this came from careful observations of the mutant phenotypes. A common feature of mutations in all of these genes is that they do not result in a randomization of hair polarity, but rather in a similar complicated and abnormal stereotypic pattern (Gubb and Garcia-Bellido 1982; Adler et al. 2000). That the abnormal patterns were so similar suggested that these genes all functioned in the same process (Wong and Adler 1993). The mutant phenotypes differed in that the vast majority of PCP mutant wing cells form a single hair, while many PPE mutant wing cells form two or three hairs. Mutations in PPE genes are epistatic to both loss- and gain-of-function mutations in PCP genes (Wong and Adler 1993; Lee and Adler 2002). Further evidence that the PPE genes function downstream of the PCP genes comes from the analysis of protein localization. PPE gene function is not needed for the proper asymmetric localization of PCP proteins (Usui et al. 1999; Strutt 2001; Tree et al. 2002; Collier et al. 2005) but in contrast PCP gene function is essential for the asymmetric accumulation of PPE proteins (Adler et al. 2004; Strutt and Warrington 2008). Further, the PCP genes/proteins instruct the localization of the PPE proteins (Adler et al. 2004).The multiple-wing-hairs (mwh) gene is thought to function downstream of both the PCP and PPE genes (Wong and Adler 1993). This conclusion comes from analyses that are similar to those that established that the PPE genes function downstream of the PCP genes. The overall hair polarity pattern of mwh mutant wings shares the same complicated and abnormal stereotypic hair polarity pattern seen in PCP and PPE mutants. However, mwh cells differ by producing a larger number of hairs (typically three to four hairs) (Wong and Adler 1993). mwh mutations are epistatic to mutations in both the PCP and PPE genes and mwh is not required for the asymmetric accumulation of either PCP or PPE proteins (Usui et al. 1999; Strutt 2001; Adler et al. 2004; Strutt and Warrington 2008).The mwh gene was recently determined to encode a novel G protein binding–formin homology 3 (GBD-FH3) protein with a complex accumulation pattern in wing cells (Strutt and Warrington 2008; Yan et al. 2008). Prior to hair initiation Mwh accumulates along the proximal side of wing cells and during hair growth Mwh accumulates in the growing hair. Temperature-shift experiments with a temperature-sensitive allele provided evidence for two temporally separate mwh functions and it was proposed that the two accumulation patterns were associated with the two temporal functions (Yan et al. 2008). Here we show that the early proximal accumulation of Mwh requires the function of the PCP and PPE genes (a result also seen previously in Strutt and Warrington 2008), while the hair accumulation of Mwh is largely independent of these two groups of genes providing further genetic evidence for Mwh having two independent functions.How does the Mwh protein accumulate proximally? An obvious possibility is that Mwh interacts directly with one or more of the upstream proteins and in this way is recruited to the proximal side. The PPE proteins are strong candidates to interact directly with Mwh, as they function genetically in between the PCP gene and Mwh (Wong and Adler 1993). Consistent with this possibility we found that In and Mwh interacted in the yeast two-hybrid system and that these two proteins co-immunoprecipated from wing cells. This interaction was found not to be dependent on the function of the PCP genes consistent with the data from genetic studies that both in and mwh retain at least partial function in a fz mutant wing (Wong and Adler 1993). The hypothesis that Mwh is recruited to the proximal side by interacting with In predicts that these two proteins function in close proximity to one another. Consistent with these expectations we found that an In∷Mwh fusion protein provided both In and Mwh function.     

How Entorhinal Grid Cells May Learn Multiple Spatial Scales from a Dorsoventral Gradient of Cell Response Rates in a Self-organizing Map

Place cells in the hippocampus of higher mammals are critical for spatial navigation. Recent modeling clarifies how this may be achieved by how grid cells in the medial entorhinal cortex (MEC) input to place cells. Grid cells exhibit hexagonal grid firing patterns across space in multiple spatial scales along the MEC dorsoventral axis. Signals from grid cells of multiple scales combine adaptively to activate place cells that represent much larger spaces than grid cells. But how do grid cells learn to fire at multiple positions that form a hexagonal grid, and with spatial scales that increase along the dorsoventral axis? In vitro recordings of medial entorhinal layer II stellate cells have revealed subthreshold membrane potential oscillations (MPOs) whose temporal periods, and time constants of excitatory postsynaptic potentials (EPSPs), both increase along this axis. Slower (faster) subthreshold MPOs and slower (faster) EPSPs correlate with larger (smaller) grid spacings and field widths. A self-organizing map neural model explains how the anatomical gradient of grid spatial scales can be learned by cells that respond more slowly along the gradient to their inputs from stripe cells of multiple scales, which perform linear velocity path integration. The model cells also exhibit MPO frequencies that covary with their response rates. The gradient in intrinsic rhythmicity is thus not compelling evidence for oscillatory interference as a mechanism of grid cell firing. A response rate gradient combined with input stripe cells that have normalized receptive fields can reproduce all known spatial and temporal properties of grid cells along the MEC dorsoventral axis. This spatial gradient mechanism is homologous to a gradient mechanism for temporal learning in the lateral entorhinal cortex and its hippocampal projections. Spatial and temporal representations may hereby arise from homologous mechanisms, thereby embodying a mechanistic “neural relativity” that may clarify how episodic memories are learned.     

Thresholds and Multiple Stable States in Coral Reef Community Dynamics

Multiple stable states occur when more than one type of communitycan stably persist in a single environmental regime. Simpletheoretical analyses predict multiple stable states for (1)single species dynamics via the Allee effect, (2) two-speciescompetitive interactions characterized by unstable coexistence,(3) some predator-prey interactions, and (4) some systems combiningpredation and competition. Potential examples of transitionsbetween stable states on reefs include the failure of Diademaantillarum and Acropora cervicornis to recover following catastrophicmortality, and the replacement of microalgal turf by unpalatablemacroalgae after rapid increase in the amount of substratumavailable for colonization by algae. Subtidal marine ecosystemsin general, and reefs in particular, have several attributeswhich favor the existence of multiple stable states. Studiesof transitions between states often need to rely upon poorlycontrolled, unreplicated natural "experiments," as transitionstypically require pulses of disturbance over very large spatialscales. The stability of a state must often be inferred fromanalyses of the dynamics of participants at that state, as generationtimes and the potential for further extrinsic disturbance precludethe use of persistence as an indicator of stability. The potentialfor multiple stable states strongly influences our interpretationof variability in space and time and our ability to predictreef responses to natural and man-made environmental change.     

Rostrocaudal Somatotopy in the Neural Connections Between the Lateral Hypothalamus and the Dorsal Periaqueductal Gray of the Rat Brain

Summary 1. The lateral hypothalamus (LH) and the dorsal periaqueductal gray area (dPAG) are two important brain structures involved in central cardiovascular control.2. In the present study, we searched for possible rostrocaudal somatotopy in the neural connections from the three subdivisions of the LH (anterior—LHa; tuberal—LHt and posterior—LHp) to the different rostrocaudal portions of the dPAG.3. The bidirectional neuronal tracer biotinylated-dextran-amine (BDA) was microinjected into different rostrocaudal coordinates of the dPAG (AP 3.4–2.7 mm) of male Wistar rats. One week later, animals were sacrificed and brain slices were processed and analyzed to detect neuronal efferent projections from the LH to the dPAG.4. Neuronal cell body staining was observed along all the rostrocaudal axis of the LH when BDA was microinjected in more rostral dPAG coordinates. When the BDA was microinjected into more caudal dPAG regions, labeled neurons were observed only in the caudal portion of the LH.5. Efferent projections from the LHa were directed only to the rostral portion of the dPAG. Projections from the rostral and medial portions of the LHt were also directed to the rostral dPAG, whereas both rostral and caudal dPAG received projections from the caudal portion of the LHt. Efferent projections from the anterior portion of the LHp were directed to both rostral and caudal dPAG, whereas projections from the caudal LHp were only directed to the rostral portion of the dPAG.6. The results suggest a somatotopic correlation in LH projections to the dPAG with main connections to the rostral dPAG, which are efferent from the three divisions of the LH. More caudal regions of the dPAG received afferents only from posterior sites in the LH.7. Moreover, the results point out to extensive and complex neural somatotopic projections from all LH subdivisions to different rostrocaudal portions of the dPAG, reinforcing the idea of significant functional interactions between the brain structures.     

DNA Methylation Changes Separate Allergic Patients from Healthy Controls and May Reflect Altered CD4+ T-Cell Population Structure

Altered DNA methylation patterns in CD4⁺ T-cells indicate the importance of epigenetic mechanisms in inflammatory diseases. However, the identification of these alterations is complicated by the heterogeneity of most inflammatory diseases. Seasonal allergic rhinitis (SAR) is an optimal disease model for the study of DNA methylation because of its well-defined phenotype and etiology. We generated genome-wide DNA methylation (N_patients = 8, N_controls = 8) and gene expression (N_patients = 9, N_controls = 10) profiles of CD4⁺ T-cells from SAR patients and healthy controls using Illumina''s HumanMethylation450 and HT-12 microarrays, respectively. DNA methylation profiles clearly and robustly distinguished SAR patients from controls, during and outside the pollen season. In agreement with previously published studies, gene expression profiles of the same samples failed to separate patients and controls. Separation by methylation (N_patients = 12, N_controls = 12), but not by gene expression (N_patients = 21, N_controls = 21) was also observed in an in vitro model system in which purified PBMCs from patients and healthy controls were challenged with allergen. We observed changes in the proportions of memory T-cell populations between patients (N_patients = 35) and controls (N_controls = 12), which could explain the observed difference in DNA methylation. Our data highlight the potential of epigenomics in the stratification of immune disease and represents the first successful molecular classification of SAR using CD4⁺ T cells.     

The Pyrimidine Nucleoside Phosphorylase of Mycoplasma hyorhinis and How It May Affect Nucleoside-Based Therapy

Mycoplasmas are opportunistic parasites and some species are suggested to preferentially colonize tumor tissue in cancer patients. We could demonstrate that the annotated thymidine phosphorylase (TP) gene in the genome of Mycoplasma hyorhinis encodes a pyrimidine nucleoside phosphorylase (PyNP_Hyor) that not only efficiently catalyzes thymidine but also uridine phosphorolysis. The kinetic characteristics of PyNP_Hyor-catalyzed nucleoside and nucleoside analogue (NA) phosphorolysis were determined. We demonstrated that the expression of such an enzyme in mycoplasma-infected cell cultures dramatically alters the activity of various anticancer/antiviral NAs such as 5-halogenated pyrimidine nucleosides, including 5-trifluorothymidine (TFT). Due to their close association with human cancers, the presence of mycoplasmas may markedly influence the therapeutic efficiency of nucleoside-based drugs.     

How the Dynamics and Structure of Sexual Contact Networks Shape Pathogen Phylogenies

The characteristics of the host contact network over which a pathogen is transmitted affect both epidemic spread and the projected effectiveness of control strategies. Given the importance of understanding these contact networks, it is unfortunate that they are very difficult to measure directly. This challenge has led to an interest in methods to infer information about host contact networks from pathogen phylogenies, because in shaping a pathogen''s opportunities for reproduction, contact networks also shape pathogen evolution. Host networks influence pathogen phylogenies both directly, through governing opportunities for evolution, and indirectly by changing the prevalence and incidence. Here, we aim to separate these two effects by comparing pathogen evolution on different host networks that share similar epidemic trajectories. This approach allows use to examine the direct effects of network structure on pathogen phylogenies, largely controlling for confounding differences arising from population dynamics. We find that networks with more heterogeneous degree distributions yield pathogen phylogenies with more variable cluster numbers, smaller mean cluster sizes, shorter mean branch lengths, and somewhat higher tree imbalance than networks with relatively homogeneous degree distributions. However, in particular for dynamic networks, we find that these direct effects are relatively modest. These findings suggest that the role of the epidemic trajectory, the dynamics of the network and the inherent variability of metrics such as cluster size must each be taken into account when trying to use pathogen phylogenies to understand characteristics about the underlying host contact network.     

Bridging the Gap between Single Molecule and Ensemble Methods for Measuring Lateral Dynamics in the Plasma Membrane

The lateral dynamics of proteins and lipids in the mammalian plasma membrane are heterogeneous likely reflecting both a complex molecular organization and interactions with other macromolecules that reside outside the plane of the membrane. Several methods are commonly used for characterizing the lateral dynamics of lipids and proteins. These experimental and data analysis methods differ in equipment requirements, labeling complexities, and further oftentimes give different results. It would therefore be very convenient to have a single method that is flexible in the choice of fluorescent label and labeling densities from single molecules to ensemble measurements, that can be performed on a conventional wide-field microscope, and that is suitable for fast and accurate analysis. In this work we show that k-space image correlation spectroscopy (kICS) analysis, a technique which was originally developed for analyzing lateral dynamics in samples that are labeled at high densities, can also be used for fast and accurate analysis of single molecule density data of lipids and proteins labeled with quantum dots (QDs). We have further used kICS to investigate the effect of the label size and by comparing the results for a biotinylated lipid labeled at high densities with Atto647N-strepatvidin (sAv) or sparse densities with sAv-QDs. In this latter case, we see that the recovered diffusion rate is two-fold greater for the same lipid and in the same cell-type when labeled with Atto647N-sAv as compared to sAv-QDs. This data demonstrates that kICS can be used for analysis of single molecule data and furthermore can bridge between samples with a labeling densities ranging from single molecule to ensemble level measurements.     

A P300-based Brain-Computer Interface with Stimuli on Moving Objects: Four-Session Single-Trial and Triple-Trial Tests with a Game-Like Task Design

Brain-computer interfaces (BCIs) are tools for controlling computers and other devices without using muscular activity, employing user-controlled variations in signals recorded from the user’s brain. One of the most efficient noninvasive BCIs is based on the P300 wave of the brain’s response to stimuli and is therefore referred to as the P300 BCI. Many modifications of this BCI have been proposed to further improve the BCI’s characteristics or to better adapt the BCI to various applications. However, in the original P300 BCI and in all of its modifications, the spatial positions of stimuli were fixed relative to each other, which can impose constraints on designing applications controlled by this BCI. We designed and tested a P300 BCI with stimuli presented on objects that were freely moving on a screen at a speed of 5.4°/s. Healthy participants practiced a game-like task with this BCI in either single-trial or triple-trial mode within four sessions. At each step, the participants were required to select one of nine moving objects. The mean online accuracy of BCI-based selection was 81% in the triple-trial mode and 65% in the single-trial mode. A relatively high P300 amplitude was observed in response to targets in most participants. Self-rated interest in the task was high and stable over the four sessions (the medians in the 1st/4th sessions were 79/84% and 76/71% in the groups practicing in the single-trial and triple-trial modes, respectively). We conclude that the movement of stimulus positions relative to each other may not prevent the efficient use of the P300 BCI by people controlling their gaze, e.g., in robotic devices and in video games.     

Influence of Pollen Transport Dynamics on Sire Profiles and Multiple Paternity in Flowering Plants

In many flowering plants individual fruits contain a mixture of half- and full- siblings, reflecting pollination by several fathers. To better understand the mechanisms generating multiple paternity within fruits we present a theoretical framework linking pollen carryover with patterns of pollinator movement. This ‘sire profile’ model predicts that species with more extensive pollen carryover will have a greater number of mates. It also predicts that flowers on large displays, which are often probed consecutively during a single pollinator visitation sequence, will have a lower effective number of mates. We compared these predictions with observed values for bumble bee-pollinated Mimulus ringens, which has restricted carryover, and hummingbird-pollinated Ipomopsis aggregata, which has extensive carryover. The model correctly predicted that the effective number of mates is much higher in the species with more extensive carryover. This work extends our knowledge of plant mating systems by highlighting mechanisms influencing the genetic composition of sibships.     

How Fitness Reduced,Antimicrobial Resistant Bacteria Survive and Spread: A Multiple Pig - Multiple Bacterial Strain Model

More than 30% of E. coli strains sampled from pig farms in Denmark over the last five years were resistant to the commonly used antimicrobial tetracycline. This raises a number of questions: How is this high level sustained if resistant bacteria have reduced growth rates? Given that there are multiple susceptible and resistant bacterial strains in the pig intestines, how can we describe their coexistence? To what extent does the composition of these multiple strains in individual pigs influence the total bacterial population of the pig pen? What happens to a complex population when antimicrobials are used? To investigate these questions, we created a model where multiple strains of bacteria coexist in the intestines of pigs sharing a pen, and explored the parameter limits of a stable system; both with and without an antimicrobial treatment. The approach taken is a deterministic bacterial population model with stochastic elements of bacterial distributions and transmission. The rates that govern the model are process-oriented to represent growth, excretion, and uptake from environment, independent of herd and meta-population structures. Furthermore, an entry barrier and elimination process for the individual strains in each pig were implemented. We demonstrate how competitive growth between multiple bacterial strains in individual pigs, and the transmission between pigs in a pen allow for strains of antimicrobial resistant bacteria to persist in a pig population to different extents, and how quickly they can become dominant if antimicrobial treatment is initiated. The level of spread depends in a non-linear way of the parameters that govern excretion and uptake. Furthermore, the sampling of initial distributions of strains and stochastic transmission events give rise to large variation in how homogenous and how resistant the bacterial population becomes. Most important: resistant bacteria are demonstrated to survive with a disadvantage in growth rate of well over 10%.