Mechanisms explaining transitions between tonic and phasic firing in neuronal populations as predicted by a low dimensional firing rate model

Several firing patterns experimentally observed in neural populations have been successfully correlated to animal behavior. Population bursting, hereby regarded as a period of high firing rate followed by a period of quiescence, is typically observed in groups of neurons during behavior. Biophysical membrane-potential models of single cell bursting involve at least three equations. Extending such models to study the collective behavior of neural populations involves thousands of equations and can be very expensive computationally. For this reason, low dimensional population models that capture biophysical aspects of networks are needed. \noindent The present paper uses a firing-rate model to study mechanisms that trigger and stop transitions between tonic and phasic population firing. These mechanisms are captured through a two-dimensional system, which can potentially be extended to include interactions between different areas of the nervous system with a small number of equations. The typical behavior of midbrain dopaminergic neurons in the rodent is used as an example to illustrate and interpret our results. \noindent The model presented here can be used as a building block to study interactions between networks of neurons. This theoretical approach may help contextualize and understand the factors involved in regulating burst firing in populations and how it may modulate distinct aspects of behavior.Comment: 25 pages (including references and appendices); 12 figures uploaded as separate file

Detailed phenotypic and genotypic characterization of bietti crystalline dystrophy

OBJECTIVE: To provide a detailed phenotype/genotype characterization of Bietti crystalline dystrophy (BCD). DESIGN: Observational case series. PARTICIPANTS: Twenty patients from 17 families recruited from a multiethnic British population. METHODS: Patients underwent color fundus photography, near-infrared (NIR) imaging, fundus autofluorescence (FAF) imaging, spectral domain optical coherence tomography (SD-OCT), and electroretinogram (ERG) assessment. The gene CYP4V2 was sequenced. MAIN OUTCOME MEASURES: Clinical, imaging, electrophysiologic, and molecular genetics findings. RESULTS: Patients ranged in age from 19 to 72 years (median, 40 years), with a visual acuity of 6/5 to perception of light (median, 6/12). There was wide intrafamilial and interfamilial variability in clinical severity. The FAF imaging showed well-defined areas of retinal pigment epithelium (RPE) loss that corresponded on SD-OCT to well-demarcated areas of outer retinal atrophy. Retinal crystals were not evident on FAF imaging and were best visualized with NIR imaging. Spectral domain OCT showed them to be principally located on or in the RPE/Bruch's membrane complex. Disappearance of the crystals, revealed by serial recording, was associated with severe disruption and thinning of the RPE/Bruch's membrane complex. Cases with extensive RPE degeneration (N = 5) had ERGs consistent with generalized rod and cone dysfunction, but those with more focal RPE atrophy showed amplitude reduction without delay (N = 3), consistent with restricted loss of function, or that was normal (N = 2). Likely disease-causing variants were identified in 34 chromosomes from 17 families. Seven were novel, including p.Met66Arg, found in all 11 patients from 8 families of South Asian descent. This mutation appears to be associated with earlier onset (median age, 30 years) compared with other substitutions (median age, 41 years). Deletions of exon 7 were associated with more severe disease. CONCLUSIONS: The phenotype is highly variable. Several novel variants are reported, including a highly prevalent substitution in patients of South Asian descent that is associated with earlier-onset disease. Autofluorescence showed sharply demarcated areas of RPE loss that coincided with abrupt edges of outer retinal atrophy on SD-OCT; crystals were generally situated on or in the RPE/Bruch's complex but could disappear over time with associated RPE disruption. These results support a role for the RPE in disease pathogenesis

Exploring the importance of within-canopy spatial temperature variation on transpiration predictions

Models seldom consider the effect of leaf-level biochemical acclimation to temperature when scaling forest water use. Therefore, the dependence of transpiration on temperature acclimation was investigated at the within-crown scale in climatically contrasting genotypes of Acer rubrum L., cv. October Glory (OG) and Summer Red (SR). The effects of temperature acclimation on intracanopy gradients in transpiration over a range of realistic forest growth temperatures were also assessed by simulation. Physiological parameters were applied, with or without adjustment for temperature acclimation, to account for transpiration responses to growth temperature. Both types of parameterization were scaled up to stand transpiration (expressed per unit leaf area) with an individual tree model (MAESTRA) to assess how transpiration might be affected by spatial and temporal distributions of foliage properties. The MAESTRA model performed well, but its reproducibility was dependent on physiological parameters acclimated to daytime temperature. Concordance correlation coefficients between measured and predicted transpiration were higher (0.95 and 0.98 versus 0.87 and 0.96) when model parameters reflected acclimated growth temperature. In response to temperature increases, the southern genotype (SR) transpiration responded more than the northern (OG). Conditions of elevated long-term temperature acclimation further separate their transpiration differences. Results demonstrate the importance of accounting for leaf-level physiological adjustments that are sensitive to microclimate changes and the use of provenance-, ecotype-, and/or genotype-specific parameter sets, two components likely to improve the accuracy of site-level and ecosystem-level estimates of transpiration flux

Large trees drive forest aboveground biomass variation in moist lowland forests accross the tropics

peer reviewedaudience: researcher, professional, studentAim Large trees (d.b.h. 70 cm) store large amounts of biomass. Several studies suggest that large trees may be vulnerable to changing climate, potentially leading to declining forest biomass storage. Here we determine the importance of large trees for tropical forest biomass storage and explore which intrinsic (species trait) and extrinsic (environment) variables are associated with the density of large trees and forest biomass at continental and pan-tropical scales. Location Pan-tropical. Methods Aboveground biomass (AGB) was calculated for 120 intact lowland moist forest locations. Linear regression was used to calculate variation in AGB explained by the density of large trees. Akaike information criterion weights (AICcwi) were used to calculate averaged correlation coefficients for all possible multiple regression models between AGB/density of large trees and environmental and species trait variables correcting for spatial autocorrelation. Results Density of large trees explained c. 70% of the variation in pan-tropical AGB and was also responsible for significantly lower AGB in Neotropical [287.8 (mean) 105.0 (SD) Mg ha-1] versus Palaeotropical forests (Africa 418.3 91.8 Mg ha-1; Asia 393.3 109.3 Mg ha-1). Pan-tropical variation in density of large trees and AGB was associated with soil coarseness (negative), soil fertility (positive), community wood density (positive) and dominance of wind dispersed species (positive), temperature in the coldest month (negative), temperature in the warmest month (negative) and rainfall in the wettest month (positive), but results were not always consistent among continents. Main conclusions Density of large trees and AGB were significantly associated with climatic variables, indicating that climate change will affect tropical forest biomass storage. Species trait composition will interact with these future biomass changes as they are also affected by a warmer climate. Given the importance of large trees for variation in AGB across the tropics, and their sensitivity to climate change, we emphasize the need for in-depth analyses of the community dynamics of large trees

Notch Ankyrin Repeat Domain Variation Influences Leukemogenesis and Myc Transactivation

, cell-based and structural analyses to compare the abilities of activated Notch1-4 to support T cell development, induce T cell acute lymphoblastic leukemia/lymphoma (T-ALL), and maintain T-ALL cell growth and survival., a direct Notch target that has an important role in Notch-associated T-ALL.We conclude that the leukemogenic potentials of Notch receptors vary, and that this functional difference stems in part from divergence among the highly conserved ankyrin repeats, which influence the transactivation of specific target genes involved in leukemogenesis

Pain in platin-induced neuropathies: A systematic review and meta-analysis

INTRODUCTION: Platin-induced peripheral neuropathy (PIPN) is a common cause of PN in cancer patients. The aim of this paper is to systematically review the current literature regarding PIPN, with a particular focus on epidemiological and clinical characteristics of painful PIPN, and to discuss relevant management strategies. METHODS: A systematic computer-based literature search was conducted on the PubMed database. RESULTS: This search strategy resulted in the identification of 353 articles. After the eligibility assessment, 282 articles were excluded. An additional 24 papers were identified by scanning the reference lists. In total, 95 papers met the inclusion criteria and were used for this review. The prevalence of neuropathic symptoms due to acute toxicity of oxaliplatin was estimated at 84.6%, whereas PN established after chemotherapy with platins was estimated at 74.9%. Specifically regarding pain, the reported prevalence of pain due to acute toxicity of oxaliplatin was estimated at 55.6%, whereas the reported prevalence of chronic peripheral neuropathic pain in PIPN was estimated at 49.2%. CONCLUSION: Peripheral neuropathy is a common complication in patients receiving platins and can be particularly painful. There is significant heterogeneity among studies regarding the method for diagnosing peripheral neuropathy. Nerve conduction studies are the gold standard and should be performed in patients receiving platins and complaining of neuropathic symptoms post-treatment

Targeted therapies in colorectal cancer: an integrative view by PPPM

In developed countries, colorectal cancer (CRC) is the third most common malignancy, but it is the second most frequent cause of cancer-related death. Clinicians are still faced with numerous challenges in the treatment of this disease, and future approaches which target the molecular features of the disorder will be critical for success in this disease setting. Genetic analyses of many solid tumours have shown that up to 100 protein-encoding genes are mutated. Within CRC, numerous genetic alterations have been identified in a number of pathways. Therefore, understanding the molecular pathology of CRC may present information on potential routes for treatment and may also provide valuable prognostic information. This will be particularly pertinent for molecularly targeted treatments, such as anti-vascular endothelial growth factor therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy. KRAS and BRAF mutations have been shown to predict response to anti-EGFR therapy. As EGFR can also signal via the phosphatidylinositol 3-kinase (PI3K) kinase pathway, there is considerable interest in the potential roles of members of this pathway (such as PI3K and PTEN) in predicting treatment response. Therefore, a combined approach of new techniques that allow identification of these biomarkers alongside interdisciplinary approaches to the treatment of advanced CRC will aid in the treatment decision-making process and may also serve to guide future therapeutic approaches

Large trees drive forest aboveground biomass variation in moist lowland forests across the tropics, Global

ABSTRACT Aim Large trees (d.b.h. Ն 70 cm) store large amounts of biomass. Several studies suggest that large trees may be vulnerable to changing climate, potentially leading to declining forest biomass storage. Here we determine the importance of large trees for tropical forest biomass storage and explore which intrinsic (species trait) and extrinsic (environment) variables are associated with the density of large trees and forest biomass at continental and pan-tropical scales. Location Pan-tropical. Methods Aboveground biomass (AGB) was calculated for 120 intact lowland moist forest locations. Linear regression was used to calculate variation in AGB explained by the density of large trees. Akaike information criterion weights (AICcwi) were used to calculate averaged correlation coefficients for all possible multiple regression models between AGB/density of large trees and environmental and species trait variables correcting for spatial autocorrelation. Results Density of large trees explained c. 70% of the variation in pan-tropical AGB and was also responsible for significantly lower AGB in Neotropical [287.8 (mean) Ϯ 105.0 (SD) Mg ha ). Pan-tropical variation in density of large trees and AGB was associated with soil coarseness (negative), soil fertility (positive), community wood density (positive) and dominance of wind dispersed species (positive), temperature in the coldest month (negative), temperature in the warmest month (negative) and rainfall in the wettest month (positive), but results were not always consistent among continents. Main conclusions Density of large trees and AGB were significantly associated with climatic variables, indicating that climate change will affect tropical forest biomass storage. Species trait composition will interact with these future biomass changes as they are also affected by a warmer climate. Given the importance of large trees for variation in AGB across the tropics, and their sensitivity to climate change, we emphasize the need for in-depth analyses of the community dynamics of large trees. bs_bs_banner Global Ecology and Biogeography, (Global Ecol. Biogeogr.