Neurites are the characteristic structural element of neurons that will initiate brain connectivity and elaborate information. Early in development, neurons are spherical cells but this symmetry is ...broken through the initial formation of neurites. This fundamental step is thought to rely on actin and microtubule dynamics. However, it is unclear which aspects of the complex actin behavior control neuritogenesis and which molecular mechanisms are involved. Here, we demonstrate that augmented actin retrograde flow and protrusion dynamics facilitate neurite formation. Our data indicate that a single family of actin regulatory proteins, ADF/Cofilin, provides the required control of actin retrograde flow and dynamics to form neurites. In particular, the F-actin severing activity of ADF/Cofilin organizes space for the protrusion and bundling of microtubules, the backbone of neurites. Our data reveal how ADF/Cofilin organizes the cytoskeleton to drive actin retrograde flow and thus break the spherical shape of neurons.
► Actin retrograde flow and dynamics direct neurite growth out of the neuronal sphere ► ADF/Cofilin is a key regulator of neuritogenesis during brain development ► ADF/Cofilin drives actin retrograde flow and dynamics ► ADF/Cofilin activity enables the growth of bundled microtubules to form neurites
Flynn et al. show that ADF/Cofilin regulates the actin turnover dynamics necessary for neurite formation in the developing brain. This work challenges the wide-held view that retrograde flow is primarily driven by the action of actin polymerization and myosin II.
ABSTRACT
Sulfate‐reducing bacteria (SRB) have been recognized as key players in the precipitation of calcium carbonate in lithifying microbial communities. These bacteria increase the alkalinity by ...reducing sulfate ions, and consuming organic acids. SRB also produce copious amounts of exopolymeric substances (EPS). All of these processes influence the morphology and mineralogy of the carbonate minerals. Interactions of EPS with metals, calcium in particular, are believed to be the main processes through which the extracellular matrix controls the precipitation of the carbonate minerals. SRB exopolymers were purified from lithifying mat and type cultures, and their potential role in CaCO3 precipitation was determined from acid‐base titrations and calcium‐binding experiments. Major EPS characteristics were established using infrared spectroscopy and gas chromatography to characterize the chemical functional groups and the sugar monomers composition. Our results demonstrate that all of the three SRB strains tested were able to produce large amounts of EPS. This EPS exhibited three main buffering capacities, which correspond to carboxylic acids (pKa = 3.0), sulfur‐containing groups (thiols, sulfonic and sulfinic acids – pKa = 7.0–7.1) and amino groups (pKa = 8.4–9.2). The calcium‐binding capacity of these exopolymers in solution at pH 9.0 ranged from 0.12gCa gEPS−1–0.15 gCa gEPS−1. These results suggest that SRB could play a critical role in the formation of CaCO3 in lithifying microbial mats. The unusually high sulfur content, which has not been reported for EPS before, indicates a possible strong interaction with iron. In addition to changing the saturation index through metabolic activity, our results imply that SRB affect the rock record through EPS production and its effect on the CaCO3 precipitation. Furthermore, EPS produced by SRB may account for the incorporation of metals (e.g. Sr, Fe, Mg) associated with carbonate minerals in the rock record.
Electronic or catalytic properties can be modified at the nanoscale level. Engineering efficient and specific nanomaterials requires the ability to study their complex structure–property ...relationships. Here, Bragg coherent diffraction imaging was used to measure the three‐dimensional shape and strain of platinum nanoparticles with a diameter smaller than 30 nm, i.e. significantly smaller than any previous study. This was made possible by the realization of the Extremely Brilliant Source of ESRF, The European Synchrotron. This work demonstrates the feasibility of imaging the complex structure of very small particles in three dimensions and paves the way towards the observation of realistic catalytic particles.
This work demonstrates three‐dimensional Bragg coherent diffraction imaging of single 20 nm Pt particles at the ID01‐EBS beamline of ESRF.
•Effective AES often require spatial coordination and collaboration.•In governance of AES, tasks can be distributed between actors, including farmer groups.•We analysed case studies in five EU member ...states: FR, BE, GE, EN and NL.•Spatial coordination is often done by professional organisations.•Learning from experiences is needed for adaptive governance of AES.
Several studies show that agri-environment schemes (AES) are likely to be more effective if they are designed at the landscape scale. However, this requires spatial coordination of environmental management across multiple farm holdings and collaboration among governmental and other actors, including, possibly, groups of farmers. In this study we analyse alternative approaches to spatial coordination and collaboration. Through case studies from five EU member states in North West Europe we analysed collaborative governance arrangements, from the perspective of the distribution of governance tasks among collaborating actors and changes to these over time. Of these governance tasks, spatial coordination had our particular interest. The collaborative governance arrangements were shaped in various ways. In four out of five case studies a group of farmers had become involved in the performance of more governance tasks over time. In all cases a professional(ized) organisation (governmental organisation or a group of farmers) was responsible for spatial coordination, possibly due to the complexities inherent to a landscape approach. In relation to the change of schemes over time, we argue that adaptive collaborative governance, incorporating learning, monitoring and evaluation in the governance arrangements, is key to effective agri- environmental management.
Innate immunity represents the first step of activation of the immune system and dictates the quality of adaptive immune responses. Studies have reported links between systemic inflammatory or innate ...immune markers and prognosis in patients with lung cancer. To our knowledge, the prospective and concomitant study of these systemic markers has never been performed.
Advanced treatment-naive non–small cell lung cancer (NSCLC) patients eligible for first-line platinum-based chemotherapy were prospectively included from December 2012 to July 2015 (N = 148). Blood samples of patients were collected before the first cycle for fresh NK cell phenotyping. Peripheral blood mononuclear cells were cryopreserved for natural cytotoxicity receptor (NCR) genotyping as well as sera for NCR's ligand quantification. Data on leukocytes, neutrophils and monocyte counts and lactate dehydrogenase (LDH) levels were extracted from electronic medical records.
Among all studied markers, monocytosis, neutrophilia, leucocytosis, high LDH and sBAG6 levels and reduced levels of NCR3 transcripts were associated with poor overall survival (OS) in univariate analysis. The levels of NCR3 transcripts was linked to age, number of metastatic sites, monocyte counts, LDH and sBAG6 levels. Neutrophilia was associated to high sBAG6 levels. NCR3 was the unique innate immune parameter that remained as an independent factor associated with both OS (P = 0.003) and progression-free survival (P = 0.009) in the multivariate analysis.
This study brought evidence that these biomarkers are entangled; parameters associated with an inflammatory process were related to reduced levels of NCR3 transcripts. Finally, the level of NCR3 transcripts was independently associated with outcomes in treatment-naive patients with advanced NSCLC.
•Natural killer and systemic innate immune markers are entangled in non–small cell lung cancer patients.•These markers have an impact on patient's clinical outcomes, mainly NKp30 receptor.•Higher NCR3 transcript (NKp30) is an independent prognostic factor of progression-free survival and overall survival.•Lower NCR3 is related to inflammatory status and is associated with poor outcomes.•Targeting these innate immune markers could represent a good therapeutic strategy.
•Modern morphometrics allows the recognition of close or cryptic forms of arthropods.•The landmark approach can hardly apply to unwinged arthropods or juvenile stages.•We show that the outline ...approach provides similar or higher discrimination scores.•Outline-based approach would allow the study of both more organs and more organisms.
Modern methods allow a geometric representation of forms, separating size and shape. In entomology, as well as in many other fields involving arthropod studies, shape variation has proved useful for species identification and population characterization. In medical entomology, it has been applied to very specific questions such as population structure, reinfestation of insecticide-treated areas and cryptic species recognition. For shape comparisons, great importance is given to the quality of landmarks in terms of comparability. Two conceptually and statistically separate approaches are: (i) landmark-based morphometrics, based on the relative position of a few anatomical “true” or “traditional” landmarks, and (ii) outline-based morphometrics, which captures the contour of forms through a sequence of close “pseudo-landmarks”.
Most of the studies on insects of medical, veterinary or economic importance make use of the landmark approach. The present survey makes a case for the outline method, here based on elliptic Fourier analysis. The collection of pseudo-landmarks may require the manual digitization of many points and, for this reason, might appear less attractive. It, however, has the ability to compare homologous organs or structures having no landmarks at all. This strength offers the possibility to study a wider range of anatomical structures and thus, a larger range of arthropods.
We present a few examples highlighting its interest for separating close or cryptic species, or characterizing conspecific geographic populations, in a series of different vector organisms. In this simple application, i.e. the recognition of close or cryptic forms, the outline approach provided similar scores as those obtained by the landmark-based approach.
A novel miniaturized biaxial deformation rig is presented. It allows one to apply in-plane biaxial stress states with arbitrary stress ratios and to perform strain path changes on thin-sheet metals. ...The device is optimized for
in situ
usage inside a scanning electron microscope and at synchrotron beam lines. The sample has a cruciform shape and the geometry is optimized with the aid of finite element simulations. A proof-of-principle experiment confirms the successful operation of this rig.
15q11.2 Deletions and duplications have been linked to autism spectrum disorder (ASD), schizophrenia, and intellectual disability (ID). Recent evidence suggests that dysfunctional Cytoplasmic FMR1 ...Interacting Protein 1 (CYFIP1) contributes to the clinical phenotypes observed in individuals with 15q11.2 deletion/duplication syndrome. CYFIP1 plays crucial roles in neuronal development and brain connectivity, promoting actin polymerization and regulating local protein synthesis. However, the impact of single nucleotide variants in CYFIP1 to neurodevelopmental disorders is limited.
Here, we report a family with two probands exhibiting ID, ASD, spastic tetraparesis, and brain morphology defects carrying biallelic missense point mutations in the CYFIP1 gene. We used skin fibroblasts from one of the proband, parents, and typically developing individuals to investigate the effect of the variants on the functionality of CYFIP1. In addition, we generated Drosophila knock-in mutants to address the effect of the variants in vivo and gain insight into the molecular mechanism underlying the clinical phenotype.
Our study revealed that the two missense variants are in protein domains responsible for maintaining the interaction within the wave regulatory complex (WRC). Molecular and cellular analyses in skin fibroblasts from one proband showed deficits in actin polymerization. The fly model for these mutations exhibited abnormal brain morphology and F-actin loss and recapitulated the core behavioral symptoms, such as deficits in social interaction and motor coordination.
Our findings suggest that the two CYFIP1 variants contribute to the clinical phenotype observed in the proband that reflects deficits in actin-mediated brain development processes.
ObjectivesTo measure the use of healthcare services and assistive devices by centenarians in five countries.DesignCross-sectional study using a survey questionnaire.SettingCommunity-dwelling and ...institutionalised centenarians living in Japan, France, Switzerland, Sweden and Denmark.Participants1253 participants aged 100 or in their 100th year of life, of whom 1004 (80.1%) were female and 596 (47.6%) lived in institutions.Main outcome measuresRecent use of medical visits, nursing care at home, home-delivered meals, acute care hospital stays overnight, professional assessments such as sight tests, mobility aids and other assistive devices. A set of national healthcare system indicators was collected to help interpret differences between countries.ResultsThere was considerable variability in the healthcare services and assistive devices used by centenarians depending on their country and whether they were community-dwelling or institutionalised. In contrast to the relatively homogeneous rates of hospitalisation in the past year (around 20%), community-dwelling centenarians reported widely ranging rates of medical visits in the past 3 months (at least one visit, from 32.2% in Japan to 86.6% in France). The proportion of community-dwellers using a mobility device to get around indoors (either a walking aid or a wheelchair) ranged from 48.3% in Japan to 79.2% in Sweden. Participants living in institutions and reporting the use of a mobility device ranged from 78.6% in Japan to 98.2% in Denmark.ConclusionsOur findings suggest major differences in care received by centenarians across countries. Some may result from the characteristics of national healthcare systems, especially types of healthcare insurance coverage and the amounts of specific resources available. However, unexplored factors also seem to be at stake and may be partly related to personal health and cultural differences.
Silvoarable agroforestry, the integration of trees and arable crops on the same area, has the potential to offer production, ecological, and societal benefits. However, the uptake of such systems in ...Europe has been limited by a combination of unsupportive policies and uncertainty concerning their productivity, profitability, and environmental impact. Faced with a lack of experimental data, the parameter-sparse Yield-SAFE model offers one method for generating plausible yield data and improving understanding of production in mixed tree–crop systems under European conditions. The applicability of the model was examined by: (i) selecting two contrasting sites in France and the UK with measured agricultural, silvoarable and/or forestry data, (ii) implementing the model in a software package, and (iii) inputting data and parameters on the climate, soils, management regime, and tree and crop types. Following calibration, Yield-SAFE provided credible descriptions of measured arable and tree (
Populus spp.) yields in the monoculture and silvoarable systems at the two sites. An examination of the response of the model to changes in model parameters and environmental and management data showed that silvoarable crop yields were most sensitive to variations in tree parameters. Increased soil depths increased timber yields, and increasing stand density increased stand volume whilst decreasing individual tree volume. In all the simulations, the model predicted greater efficiency in use of land, i.e. greater land equivalent ratios, when trees and crops were combined rather than grown as sole crops. These results, supported by the sparse experimental data available, indicate that agroforestry provides a method of increasing food, timber and biomass production from limited land resources in Europe.
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