KDM2B/FBXL10 targets c-Fos for ubiquitylation and degradation in response to mitogenic stimulation.

KDM2B (also known as FBXL10) controls stem cell self-renewal, somatic cell reprogramming and senescence, and tumorigenesis. KDM2B contains multiple functional domains, including a JmjC domain that catalyzes H3K36 demethylation and a CxxC zinc-finger that recognizes CpG islands and recruits the polycomb repressive complex 1. Here, we report that KDM2B, via its F-box domain, functions as a subunit of the CUL1-RING ubiquitin ligase (CRL1/SCF(KDM2B)) complex. KDM2B targets c-Fos for polyubiquitylation and regulates c-Fos protein levels. Unlike the phosphorylation of other SCF (SKP1-CUL1-F-box)/CRL1 substrates that promotes substrates binding to F-box, epidermal growth factor (EGF)-induced c-Fos S374 phosphorylation dissociates c-Fos from KDM2B and stabilizes c-Fos protein. Non-phosphorylatable and phosphomimetic mutations at S374 result in c-Fos protein which cannot be induced by EGF or accumulates constitutively and lead to decreased or increased cell proliferation, respectively. Multiple tumor-derived KDM2B mutations impaired the function of KDM2B to target c-Fos degradation and to suppress cell proliferation. These results reveal a novel function of KDM2B in the negative regulation of cell proliferation by assembling an E3 ligase to targeting c-Fos protein degradation that is antagonized by mitogenic stimulations

Fiber Orientation Estimation Guided by a Deep Network

Diffusion magnetic resonance imaging (dMRI) is currently the only tool for noninvasively imaging the brain's white matter tracts. The fiber orientation (FO) is a key feature computed from dMRI for fiber tract reconstruction. Because the number of FOs in a voxel is usually small, dictionary-based sparse reconstruction has been used to estimate FOs with a relatively small number of diffusion gradients. However, accurate FO estimation in regions with complex FO configurations in the presence of noise can still be challenging. In this work we explore the use of a deep network for FO estimation in a dictionary-based framework and propose an algorithm named Fiber Orientation Reconstruction guided by a Deep Network (FORDN). FORDN consists of two steps. First, we use a smaller dictionary encoding coarse basis FOs to represent the diffusion signals. To estimate the mixture fractions of the dictionary atoms (and thus coarse FOs), a deep network is designed specifically for solving the sparse reconstruction problem. Here, the smaller dictionary is used to reduce the computational cost of training. Second, the coarse FOs inform the final FO estimation, where a larger dictionary encoding dense basis FOs is used and a weighted l1-norm regularized least squares problem is solved to encourage FOs that are consistent with the network output. FORDN was evaluated and compared with state-of-the-art algorithms that estimate FOs using sparse reconstruction on simulated and real dMRI data, and the results demonstrate the benefit of using a deep network for FO estimation.Comment: A shorter version is accepted by MICCAI 201

ΔFosB Regulates Gene Expression and Cognitive Dysfunction in a Mouse Model of Alzheimer\u27s Disease.

Alzheimer\u27s disease (AD) is characterized by cognitive decline and 5- to 10-fold increased seizure incidence. How seizures contribute to cognitive decline in AD or other disorders is unclear. We show that spontaneous seizures increase expression of ΔFosB, a highly stable Fos-family transcription factor, in the hippocampus of an AD mouse model. ΔFosB suppressed expression of the immediate early gene c-Fos, which is critical for plasticity and cognition, by binding its promoter and triggering histone deacetylation. Acute histone deacetylase (HDAC) inhibition or inhibition of ΔFosB activity restored c-Fos induction and improved cognition in AD mice. Administration of seizure-inducing agents to nontransgenic mice also resulted in ΔFosB-mediated suppression of c-Fos, suggesting that this mechanism is not confined to AD mice. These results explain observations that c-Fos expression increases after acute neuronal activity but decreases with chronic activity. Moreover, these results indicate a general mechanism by which seizures contribute to persistent cognitive deficits, even during seizure-free periods

Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine

Background: Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphorylation of extracellular signal-regulated kinases (ERK) to look for evidence that interneurons expressing GRP were activated following intradermal injection of chloroquine into the calf, in mice that express enhanced green fluorescent protein (EGFP) in these cells. Results: Injection of chloroquine resulted in numerous Fos- or phospho-ERK (pERK) positive cells in the somatotopically appropriate part of the superficial dorsal horn. The proportion of all neurons in this region that showed Fos or pERK was 18% and 21%, respectively. However, among the GRP–EGFP, only 7% were Fos-positive and 3% were pERK-positive. As such, GRP–EGFP cells were significantly less likely than other neurons to express Fos or to phosphorylate ERK. Conclusions: Both expression of Fos and phosphorylation of ERK can be used to identify dorsal horn neurons activated by chloroquine injection. However, these results do not support the hypothesis that interneurons expressing GRP are critical components in the itch pathway

Automated identification of Fos expression

The concentration of Fos, a protein encoded by the immediate-early gene c-fos, provides a measure of synaptic activity that may not parallel the electrical activity of neurons. Such a measure is important for the difficult problem of identifying dynamic properties of neuronal circuitries activated by a variety of stimuli and behaviours. We employ two-stage statistical pattern recognition to identify cellular nuclei that express Fos in two-dimensional sections of rat forebrain after administration of antipsychotic drugs. In stage one, we distinguish dark-stained candidate nuclei from image background by a thresholding algorithm and record size and shape measurements of these objects. In stage two, we compare performance of linear and quadratic discriminants, nearest-neighbour and artificial neural network classifiers that employ functions of these measurements to label candidate objects as either Fos nuclei, two touching Fos nuclei or irrelevant background material. New images of neighbouring brain tissue serve as test sets to assess generalizability of the best derived classification rule, as determined by lowest cross-validation misclassification rate. Three experts, two internal and one external, compare manual and automated results for accuracy assessment. Analyses of a subset of images on two separate occasions provide quantitative measures of inter- and intra-expert consistency. We conclude that our automated procedure yields results that compare favourably with those of the experts and thus has potential to remove much of the tedium, subjectivity and irreproducibility of current Fos identification methods in digital microscopy

La invasió verda

Plantes protagonistes de transtorns ambientals al territori valenci&agrave

First mission - towards a global harmonised in-situ data repository for forest biomass datasets validation

Global measurements of forest height, biomass are urgently needed as essential climate and ecosystem variables, but can benefit from greater co-operation between remote sensing (RS) and forest ecological communities. The Forest Observation System - FOS (https://forest-observation-system.net/ [https://forest-observation- system.net/]) is an international cooperation to establish a global in-situ forest biomass database to support earth observation and to encourage investment in relevant field-based observations and science. FOS aims to link the RS community with ecologists who measure forest biomass and estimating biodiversity in the field. The FOS aims to overcome data sharing issues and introduce a standard biomass data flow from tree-level measurement to the plot-level aggregation served in the most suitable form for the RS. Ecologists benefit from the FOS with improved access to global biomass information, data standards, gap identification and potentially improved funding opportunities to address the known gaps and deficiencies in the data. FOS closely collaborate with the CTFS-ForestGEO, the ForestPlots.net (incl. RAfNFOR, AfriTRON and T-FORCES), AusCover, TmFO and the llASA network. FOS is an open initiative with other networks and teams most welcome to join. The online database provides open access for forest plot location, canopy height and above-ground biomass. Plot size is 0.25ha or larger. Comparison of plot biomass data with available global and regional maps (incl. Kindermann et al., 2013; Thurner et al., 2013; Saatchi et al., 2011; Baccini et al., 2012; Avitabile et al., 2016; Hu et al., 2016; Santoro et al., 2018) shows wide range of uncertainties associated with biomass estimation

Immunohistochemical C-FOS expression and autoradiography to study galnin/neuropeptide y Y1 receptor-receptor interactions in the amygdala

We have shown Galanin(GAL)/Neuropeptide Y Y1 receptor(Y1) interactions in the nucleus tractus solitarius and the arcuate nucleus. Since both peptides play an important role in mood disorders, the aim of this work was to study GAL/Y1 interactions in the amygdala(AMY), key nucleus for fear, mood, and motivation. We have combined the analysis of the expression of c-Fos immunoreactivity(c-Fos IR) with an autoradiographic study in the AMY. Groups of anaesthetized rats (n=4) received intracerebroventricular injections(icv) of GAL(3nmol) and the Y1 agonist Leu31-Pro34NPY(3nmol) alone or in combination, and were sacrificed 90 minutes after the injections. Immunohistochemical detection of c-Fos protein(1:5000) in AMY sections and stereological analysis were performed in: Basal(BA), lateral(LA), Central [lateral capsular subdivision(CeC), lateral intermediate subdivision(CeI), medial subdivision(CeM)] and the medial paracapsular intercalated(ITC) subnuclei of the AMY. For Autoradiography, rats (n=6) were sacrificed 15 minutes after icv injections of GAL(3nmol) and AMY sections were incubated with Y1 agonist [125I]-Leu31-Pro34-PPY (25 pM). Autoradiograms were analyzed using the NIH image analysis system. Student’s unpaired t- test and ANOVA followed by Newman-Keuls were used, respectively. We observed within the AMY that GAL increased c-Fos IR in ITC and CeC; the Y1 agonist induced both, an increase of c-Fos IR in BA and CeC and a decrease of c-Fos IR in LA and ITC. The coadministration of both peptides induced a specific effect in the ITC, significantly decreasing the c-Fos expression (P<0,05) induced by GAL or the Y1 agonist alone. Moreover, we observed that GAL significantly increased (p<0,05) the Y1 receptor agonist binding [I125]Leu31Pro34-PYY in the AMY. These results demonstrate an interaction between GAL and Y1 at the cellular and receptor level in the AMY and suggest that endogenous GAL and NPY system might interact to regulate emotional behaviours.Spanish CVI6476, TV3-Marató 090130/31/32 and Universidad de Málaga (Campus de Excelencia Internacional Andalucía Tech

Enhancement of capacity of farmer organizations for sustainable irrigation systems in Anuradhapura and Kurunegala districts

Over the past decades public investment in major, medium and minor irrigation systems has not yielded the expected results. The solution to the growing water crisis lies in the institutional reform of existing social systems so as to manage the demand for water. In recent times, there has been an emphasis on capacity-building of farmer organizations (FO) in irrigation projects. This study focuses on investigating the institutional capacities of FOs in irrigation systems in the Anuradhapura and Kurunegala districts. Primary data was collected from a stratified random sample of 48 FOs selected from major, medium and minor irrigation systems in the Anuradhapura and Kunurnegala districts during 2008. The Group Dynamics Effectiveness Index (GDEI) of FOs was developed by weighing the significance of important parameters and employed in the calculation of the overall effectiveness of FOs. Most of the FO members in both districts were landowners and there was a powerful dominance from farmers. Generally, the marginal participation in FO activities was about 38 % in both districts. The most common causes for the low participation were the lack of accountability and transparency of the functions of FOs. Farmer organizations (FOs) in major and medium irrigation systems had 51 % and 29 % higher GDEI, respectively, than FOs in minor irrigation systems. The values of ‘Gini Coefficients’ in major, medium and minor irrigation systems were 0.38, 0.43 and 0.48, respectively, thus indicating that FOs play an important role in minimizing inequalities among farmers. There was no significant difference in water productivity (0.19–0.20 $/m3) between major and medium irrigation systems, but the water productivity was low (0.07$/m3) in minor irrigation systems. Farmer organizations (FOs) with medium size (30–40 members) and economically homogeneous members had better irrigation management. Chi-square results show that while the income equity had no significant effect on the overall GDEI, the participation rate and water productivity that reflects the success of operation and maintenance (O & M) had a significant impact of 5 % and 10 % probability levels to the GDEI of FOs. There is a need to establish strong linkages between the FOs and the Irrigation Department for successful irrigation management. The behavioral change that is required to facilitate the adoption of technology can be effected through institutional changes. It is recommended that FOs need a lot of capacity building in technical and institutional issues to sustain the irrigation systems.Length: pp.7-17Farmers organizationsCapacity buildingIrrigation systems