Differential patterns of functional and structural plasticity within and between inferior frontal gyri support training-induced improvements in inhibitory control proficiency.

Ample evidence indicates that inhibitory control (IC), a key executive component referring to the ability to suppress cognitive or motor processes, relies on a right-lateralized fronto-basal brain network. However, whether and how IC can be improved with training and the underlying neuroplastic mechanisms remains largely unresolved. We used functional and structural magnetic resonance imaging to measure the effects of 2 weeks of training with a Go/NoGo task specifically designed to improve frontal top-down IC mechanisms. The training-induced behavioral improvements were accompanied by a decrease in neural activity to inhibition trials within the right pars opercularis and triangularis, and in the left pars orbitalis of the inferior frontal gyri. Analyses of changes in brain anatomy induced by the IC training revealed increases in grey matter volume in the right pars orbitalis and modulations of white matter microstructure in the right pars triangularis. The task-specificity of the effects of training was confirmed by an absence of change in neural activity to a control working memory task. Our combined anatomical and functional findings indicate that differential patterns of functional and structural plasticity between and within inferior frontal gyri enhanced the speed of top-down inhibition processes and in turn IC proficiency. The results suggest that training-based interventions might help overcoming the anatomic and functional deficits of inferior frontal gyri manifesting in inhibition-related clinical conditions. More generally, we demonstrate how multimodal neuroimaging investigations of training-induced neuroplasticity enable revealing novel anatomo-functional dissociations within frontal executive brain networks. Hum Brain Mapp 36:2527-2543, 2015. © 2015 Wiley Periodicals, Inc.

Fluctuation-Driven Neural Dynamics Reproduce Drosophila Locomotor Patterns.

The neural mechanisms determining the timing of even simple actions, such as when to walk or rest, are largely mysterious. One intriguing, but untested, hypothesis posits a role for ongoing activity fluctuations in neurons of central action selection circuits that drive animal behavior from moment to moment. To examine how fluctuating activity can contribute to action timing, we paired high-resolution measurements of freely walking Drosophila melanogaster with data-driven neural network modeling and dynamical systems analysis. We generated fluctuation-driven network models whose outputs-locomotor bouts-matched those measured from sensory-deprived Drosophila. From these models, we identified those that could also reproduce a second, unrelated dataset: the complex time-course of odor-evoked walking for genetically diverse Drosophila strains. Dynamical models that best reproduced both Drosophila basal and odor-evoked locomotor patterns exhibited specific characteristics. First, ongoing fluctuations were required. In a stochastic resonance-like manner, these fluctuations allowed neural activity to escape stable equilibria and to exceed a threshold for locomotion. Second, odor-induced shifts of equilibria in these models caused a depression in locomotor frequency following olfactory stimulation. Our models predict that activity fluctuations in action selection circuits cause behavioral output to more closely match sensory drive and may therefore enhance navigation in complex sensory environments. Together these data reveal how simple neural dynamics, when coupled with activity fluctuations, can give rise to complex patterns of animal behavior.

Patterns of care in recurrent glioblastoma in Switzerland: a multicentre national approach based on diagnostic nodes.

Despite moderate improvements in outcome of glioblastoma after first-line treatment with chemoradiation recent clinical trials failed to improve the prognosis of recurrent glioblastoma. In the absence of a standard of care we aimed to investigate institutional treatment strategies to identify similarities and differences in the pattern of care for recurrent glioblastoma. We investigated re-treatment criteria and therapeutic pathways for recurrent glioblastoma of eight neuro-oncology centres in Switzerland having an established multidisciplinary tumour-board conference. Decision algorithms, differences and consensus were analysed using the objective consensus methodology. A total of 16 different treatment recommendations were identified based on combinations of eight different decision criteria. The set of criteria implemented as well as the set of treatments offered was different in each centre. For specific situations, up to 6 different treatment recommendations were provided by the eight centres. The only wide-range consensus identified was to offer best supportive care to unfit patients. A majority recommendation was identified for non-operable large early recurrence with unmethylated MGMT promoter status in the fit patients: here bevacizumab was offered. In fit patients with late recurrent non-operable MGMT promoter methylated glioblastoma temozolomide was recommended by most. No other majority recommendations were present. In the absence of strong evidence we identified few consensus recommendations in the treatment of recurrent glioblastoma. This contrasts the limited availability of single drugs and treatment modalities. Clinical situations of greatest heterogeneity may be suitable to be addressed in clinical trials and second opinion referrals are likely to yield diverging recommendations.

How to describe species richness patterns for bryophyte conservation?

A large amount of data for inconspicuous taxa is stored in natural history collections; however, this information is often neglected for biodiversity patterns studies. Here, we evaluate the performance of direct interpolation of museum collections data, equivalent to the traditional approach used in bryophyte conservation planning, and stacked species distribution models (S-SDMs) to produce reliable reconstructions of species richness patterns, given that differences between these methods have been insufficiently evaluated for inconspicuous taxa. Our objective was to contrast if species distribution models produce better inferences of diversity richness than simply selecting areas with the higher species numbers. As model species, we selected Iberian species of the genus Grimmia (Bryophyta), and we used four well-collected areas to compare and validate the following models: 1) four Maxent richness models, each generated without the data from one of the four areas, and a reference model created using all of the data and 2) four richness models obtained through direct spatial interpolation, each generated without the data from one area, and a reference model created with all of the data. The correlations between the partial and reference Maxent models were higher in all cases (0.45 to 0.99), whereas the correlations between the spatial interpolation models were negative and weak (-0.3 to -0.06). Our results demonstrate for the first time that S-SDMs offer a useful tool for identifying detailed richness patterns for inconspicuous taxa such as bryophytes and improving incomplete distributions by assessing the potential richness of under-surveyed areas, filling major gaps in the available data. In addition, the proposed strategy would enhance the value of the vast number of specimens housed in biological collections.

Phylogeography of competing sexual and parthenogenetic forms of a freshwater flatworm: patterns and explanations

Background: Models of the maintenance of sex predict that one reproductive strategy, sexual or parthenogenetic, should outcompete the other. Distribution patterns may reflect the outcome of this competition as well as the effect of chance and historical events. We review the distribution data of sexual and parthenogenetic biotypes of the planarian Schmidtea polychroa. Results: S. polychroa lives in allopatry or sympatry across Europe except for Central and North-Western Europe, where sexual individuals have never been reported. A phylogenetic relationship between 36 populations based on a 385 bp fragment of the mitochondrial cytochrome oxidase I gene revealed that haplotypes were often similar over large geographic distances. In North Italian lakes, however, diversity was extreme, with sequence differences of up to 5% within the same lake in both sexuals and parthenogens. Mixed populations showed "endemic" parthenogenetic lineages that presumably originated from coexisting sexuals, and distantly related ones that probably result from colonization by parthenogens independent from sexuals. Conclusions: Parthenogens originated repeatedly from sexuals, mainly in Italy, but the same may apply to other Mediterranean regions (Spain, Greece). The degree of divergence between populations suggests that S. polychroa survived the ice ages in separate ice-free areas in Central, Eastern and Southern Europe and re-colonised Europe after the retreat of the major glaciers. Combining these results with those based on nuclear markers, the data suggest that repeated hybridisation between sexuals and parthenogenetic lineages in mixed populations maintains high levels of genetic diversity in parthenogens. This can explain why parthenogens persist in populations that were originally sexual. Exclusive parthenogenesis in central and western populations suggests better colonisation capacity, possibly because of inbreeding costs as well

Identification of imaging selection patterns in acute ischemic stroke patients and the influence on treatment and clinical trial enrollment decision making.

BACKGROUND AND PURPOSE: For the STroke Imaging Research (STIR) and VISTA-Imaging Investigators The purpose of this study was to collect precise information on the typical imaging decisions given specific clinical acute stroke scenarios. Stroke centers worldwide were surveyed regarding typical imaging used to work up representative acute stroke patients, make treatment decisions, and willingness to enroll in clinical trials. METHODS: STroke Imaging Research and Virtual International Stroke Trials Archive-Imaging circulated an online survey of clinical case vignettes through its website, the websites of national professional societies from multiple countries as well as through email distribution lists from STroke Imaging Research and participating societies. Survey responders were asked to select the typical imaging work-up for each clinical vignette presented. Actual images were not presented to the survey responders. Instead, the survey then displayed several types of imaging findings offered by the imaging strategy, and the responders selected the appropriate therapy and whether to enroll into a clinical trial considering time from onset, clinical presentation, and imaging findings. A follow-up survey focusing on 6 h from onset was conducted after the release of the positive endovascular trials. RESULTS: We received 548 responses from 35 countries including 282 individual centers; 78% of the centers originating from Australia, Brazil, France, Germany, Spain, United Kingdom, and United States. The specific onset windows presented influenced the type of imaging work-up selected more than the clinical scenario. Magnetic Resonance Imaging usage (27-28%) was substantial, in particular for wake-up stroke. Following the release of the positive trials, selection of perfusion imaging significantly increased for imaging strategy. CONCLUSIONS: Usage of vascular or perfusion imaging by Computed Tomography or Magnetic Resonance Imaging beyond just parenchymal imaging was the primary work-up (62-87%) across all clinical vignettes and time windows. Perfusion imaging with Computed Tomography or Magnetic Resonance Imaging was associated with increased probability of enrollment into clinical trials for 0-3 h. Following the release of the positive endovascular trials, selection of endovascular only treatment for 6 h increased across all clinical vignettes.

Geographic patterns of genetic variation in a broadly distributed marine vertebrate: new insights into loggerhead turtle stock structure from expanded mitochondrial DNA sequences

Previous genetic studies have demonstrated that natal homing shapes the stock structure of marine turtle nesting populations. However, widespread sharing of common haplotypes based on short segments of the mitochondrial control region often limits resolution of the demographic connectivity of populations. Recent studies employing longer control region sequences to resolve haplotype sharing have focused on regional assessments of genetic structure and phylogeography. Here we synthesize available control region sequences for loggerhead turtles from the Mediterranean Sea, Atlantic, and western Indian Ocean basins. These data represent six of the nine globally significant regional management units (RMUs) for the species and include novel sequence data from Brazil, Cape Verde, South Africa and Oman. Genetic tests of differentiation among 42 rookeries represented by short sequences (380 bp haplotypes from 3,486 samples) and 40 rookeries represented by long sequences (~800 bp haplotypes from 3,434 samples) supported the distinction of the six RMUs analyzed as well as recognition of at least 18 demographically independent management units (MUs) with respect to female natal homing. A total of 59 haplotypes were resolved. These haplotypes belonged to two highly divergent global lineages, with haplogroup I represented primarily by CC-A1, CC-A4, and CC-A11 variants and haplogroup II represented by CC-A2 and derived variants. Geographic distribution patterns of haplogroup II haplotypes and the nested position of CC-A11.6 from Oman among the Atlantic haplotypes invoke recent colonization of the Indian Ocean from the Atlantic for both global lineages. The haplotypes we confirmed for western Indian Ocean RMUs allow reinterpretation of previous mixed stock analysis and further suggest that contemporary migratory connectivity between the Indian and Atlantic Oceans occurs on a broader scale than previously hypothesized. This study represents a valuable model for conducting comprehensive international cooperative data management and research in marine ecology.

Degradación de T-patterns en estudios observacionales: Un estudio sobre la eficacia en el ataque de fútbol sala

Una de las técnicas analíticas más novedosas en el ámbito de la metodología observacional es la que permite la detección de T-patterns (estructuras regulares de conducta) mediante el software THEME, que analiza datos observacionales en búsqueda de relaciones de intervalo crítico en sentido ascendente (desde T-pattern simples, dos eventos que se relacionan en un primer nivel, a T-patterns complejos constituidos por diferentes eventos relacionados en distintos niveles). En el presente artículo se analiza esta cuestión, la degradación de los T-patterns, que hasta el momento ha sido puntualmente estudiada. Para ello, se utiliza el muestreo observacional constituido por el conjunto de las secuencias que acaban en gol (n= 23) protagonizadas por el F.C. Barcelona durante el Play Off Final de la liga española 2012-13 de fútbol sala. De esta forma este trabajo satisface un segundo objetivo, en este caso disciplinar, de analizar la e'cacia en la construcción de la fase ofensiva en el fútbol sala; habiéndose tipi'cado que las secuencias que 'nalizan en gol se caracterizan por conseguir, mediante juego combinativo, un lanzamiento desde sector de'nición-corredor central.

Detection of Horizontal Two-Phase Flow Patterns Through a Neural Network Model

One of the main problems related to the transport and manipulation of multiphase fluids concerns the existence of characteristic flow patterns and its strong influence on important operation parameters. A good example of this occurs in gas-liquid chemical reactors in which maximum efficiencies can be achieved by maintaining a finely dispersed bubbly flow to maximize the total interfacial area. Thus, the ability to automatically detect flow patterns is of crucial importance, especially for the adequate operation of multiphase systems. This work describes the application of a neural model to process the signals delivered by a direct imaging probe to produce a diagnostic of the corresponding flow pattern. The neural model is constituted of six independent neural modules, each of which trained to detect one of the main horizontal flow patterns, and a last winner-take-all layer responsible for resolving when two or more patterns are simultaneously detected. Experimental signals representing different bubbly, intermittent, annular and stratified flow patterns were used to validate the neural model.

Low pH and calcium effects on net Na+ and K+ fluxes in two catfish species from the Amazon River (Corydoras: Callichthyidae)

The present study analyzes Na+ and K+ disturbances caused by low pH in two catfish species from the Amazon River. Corydoras adolfoi inhabits ion-poor, black-stained, low pH (3.5-4.0) waters, while C. schwartzi is native to ion-rich waters at circumneutral pH. Fish were exposed to pH 3.5 Ca2+-free, and Ca2+-enriched (~500 µmol/l) water to determine the protective effects of calcium. Net Na+ and K+ fluxes were measured in the water collected from the fish experimental chambers. C. adolfoi was unable to control the Na+ efflux at low pH, exhibiting Na+ loss up to -594 ± 84 nmol g-1 h-1 during the first hour. After 3 and 6 h, net Na+ flux increased by 7- and 23-fold, respectively. In C. schwartzi, at pH 3.5, the initial high Na+ loss (-1,063 ± 73 nmol g-1 h-1) was gradually attenuated. A K+ loss occurred in both species, but remained relatively constant throughout exposure. High [Ca2+] affected ion losses in both species. C. adolfoi had 70% loss attenuation, indicating incapacity to control Na+ efflux. In C. schwartzi, elevated [Ca2+] completely prevented the Na+ losses caused by exposure to low pH. Rather different patterns were seen for K+ fluxes, with C. adolfoi showing no K+ disruption when exposed to low pH/high [Ca2+]. Thus, C. adolfoi loses Na+ during acid exposure, but has the ability to control K+ loss, while C. schwartzi controls diffusive Na+ loss but exhibits a slightly higher K+ loss. Ion balance was influenced by [Ca2+] at low pH in C. schwartzi but not in C. adolfoi.

Patterns of intracellular cytokines in CD4 and CD8 T cells from patients with mycobacterial infections

Using a short-term bulk culture protocol designed for an intracellular-staining method based on a flow cytometry approach to the frequencies of cytokine-producing cells from tuberculosis and leprosy patients, we found distinct patterns of T cell subset expression. The method also reveals the profile of peak cytokine production and can provide simultaneous information about the phenotype of cytokine-producing cells, providing a reliable assay for monitoring the immunity of these patients. The immune response of Mycobacterium leprae and purified protein derivative (PPD) in vitro to a panel of mycobacteria-infected patients from an endemic area was assessed in primary mononuclear cell cultures. The kinetics and source of the cytokine pattern were measured at the single-cell level. IFN-gamma-, TNF-alpha-, IL-4- and IL-10-secreting T cells were intracytoplasmic evaluated in an attempt to identify M. leprae- and PPD-specific cells directly from the peripheral blood. The analysis by this approach indicated that TNF-alpha was the first (8 h) to be produced, followed by IFN-gamma (16 h), IL-10 (20 h) and IL-4 (24 h), and double-staining experiments confirmed that CD4+ were a greater source of TNF-alpha than of CD8+ T cells (P < 0.05). Both T cell subsets secreted similar amounts of IFN-gamma. We conclude that the protocol permits rapid evaluation of cytokine production by different T cell populations. The method can also be used to define immune status in non-infected and contact individuals.

Evaluation of anti-Wnt/β-catenin signaling agents by pGL4-TOP transfected stable cells with a luciferase reporter system

Refractory and relapsed leukemia is a major problem during cancer therapy, which is due to the aberrant activation of Wnt/β-catenin signaling pathway. Activation of this pathway is promoted by wingless (Wnt) proteins and induces co-activator β-catenin binding to lymphoid enhancer factor (LEF)/T-cell factor protein (TCF). To provide a convenient system for the screening of anti-Wnt/β-catenin agents, we designed a bi-functional pGL4-TOP reporter plasmid that contained 3X β-catenin/LEF/TCF binding sites and a selectable marker. After transfection and hygromycin B selection, HEK 293-TOP and Jurkat-TOP stable clones were established. The luciferase activity in the stable clone was enhanced by the recombinant Wnt-3A (rWnt-3A; 100-400 ng/mL) and GSK3β inhibitor (2’Z,3’E)-6-bromoindirubin-3’-oxime (BIO; 5 µM) but was inhibited by aspirin (5 mM). Using this reporter model, we found that norcantharidin (NCTD; 100 µM) reduced 80% of rWnt-3A-induced luciferase activity. Furthermore, 50 µM NCTD inhibited 38% of BIO-induced luciferase activity in Jurkat-TOP stable cells. Employing ³H-thymidine uptake assay and Western blot analysis, we confirmed that NCTD (50 µM) significantly inhibited proliferation of Jurkat cells by 64%, which are the dominant β-catenin signaling cells and decreased β-catenin protein in a concentration-dependent manner. Thus, we established a stable HEK 293-TOP clone and successfully used it to identify the Wnt/β-catenin signaling inhibitor NCTD.

Relationships between dendritic morphology, spatial distribution and firing patterns in rat layer 1 neurons

The cortical layer 1 contains mainly small interneurons, which have traditionally been classified according to their axonal morphology. The dendritic morphology of these cells, however, has received little attention and remains ill defined. Very little is known about how the dendritic morphology and spatial distribution of these cells may relate to functional neuronal properties. We used biocytin labeling and whole cell patch clamp recordings, associated with digital reconstruction and quantitative morphological analysis, to assess correlations between dendritic morphology, spatial distribution and membrane properties of rat layer 1 neurons. A total of 106 cells were recorded, labeled and subjected to morphological analysis. Based on the quantitative patterns of their dendritic arbor, cells were divided into four major morphotypes: horizontal, radial, ascendant, and descendant cells. Descendant cells exhibited a highly distinct spatial distribution in relation to other morphotypes, suggesting that they may have a distinct function in these cortical circuits. A significant difference was also found in the distribution of firing patterns between each morphotype and between the neuronal populations of each sublayer. Passive membrane properties were, however, statistically homogeneous among all subgroups. We speculate that the differences observed in active membrane properties might be related to differences in the synaptic input of specific types of afferent fibers and to differences in the computational roles of each morphotype in layer 1 circuits. Our findings provide new insights into dendritic morphology and neuronal spatial distribution in layer 1 circuits, indicating that variations in these properties may be correlated with distinct physiological functions.