Isotropic reconstruction of 3D fluorescence microscopy images using convolutional neural networks

Fluorescence microscopy images usually show severe anisotropy in axial versus lateral resolution. This hampers downstream processing, i.e. the automatic extraction of quantitative biological data. While deconvolution methods and other techniques to address this problem exist, they are either time consuming to apply or limited in their ability to remove anisotropy. We propose a method to recover isotropic resolution from readily acquired anisotropic data. We achieve this using a convolutional neural network that is trained end-to-end from the same anisotropic body of data we later apply the network to. The network effectively learns to restore the full isotropic resolution by restoring the image under a trained, sample specific image prior. We apply our method to $3$ synthetic and $3$ real datasets and show that our results improve on results from deconvolution and state-of-the-art super-resolution techniques. Finally, we demonstrate that a standard 3D segmentation pipeline performs on the output of our network with comparable accuracy as on the full isotropic data

Resilience of three-dimensional sinusoidal networks in liver tissue

Can three-dimensional, microvasculature networks still ensure blood supply if individual links fail? We address this question in the sinusoidal network, a plexus-like microvasculature network, which transports nutrient-rich blood to every hepatocyte in liver tissue, by building on recent advances in high-resolution imaging and digital reconstruction of adult mice liver tissue. We find that the topology of the three-dimensional sinusoidal network reflects its two design requirements of a space-filling network that connects all hepatocytes, while using shortest transport routes: sinusoidal networks are sub-graphs of the Delaunay graph of their set of branching points, and also contain the corresponding minimum spanning tree, both to good approximation. To overcome the spatial limitations of experimental samples and generate arbitrarily-sized networks, we developed a network generation algorithm that reproduces the statistical features of 0.3-mm-sized samples of sinusoidal networks, using multi-objective optimization for node degree and edge length distribution. Nematic order in these simulated networks implies anisotropic transport properties, characterized by an empirical linear relation between a nematic order parameter and the anisotropy of the permeability tensor. Under the assumption that all sinusoid tubes have a constant and equal flow resistance, we predict that the distribution of currents in the network is very inhomogeneous, with a small number of edges carrying a substantial part of the flow-a feature known for hierarchical networks, but unexpected for plexus-like networks. We quantify network resilience in terms of a permeability-at-risk, i.e., permeability as function of the fraction of removed edges. We find that sinusoidal networks are resilient to random removal of edges, but vulnerable to the removal of high-current edges. Our findings suggest the existence of a mechanism counteracting flow inhomogeneity to balance metabolic load on the liver

The High Mobility Group A1 (HMGA1) Chromatin Architectural Factor Modulates Nuclear Stiffness in Breast Cancer Cells

13siPlasticity is an essential condition for cancer cells to invade surrounding tissues. The nucleus is the most rigid cellular organelle and it undergoes substantial deformations to get through environmental constrictions. Nuclear stiffness mostly depends on the nuclear lamina and chromatin, which in turn might be affected by nuclear architectural proteins. Among these is the HMGA1 (High Mobility Group A1) protein, a factor that plays a causal role in neoplastic transformation and that is able to disentangle heterochromatic domains by H1 displacement. Here we made use of atomic force microscopy to analyze the stiffness of breast cancer cellular models in which we modulated HMGA1 expression to investigate its role in regulating nuclear plasticity. Since histone H1 is the main modulator of chromatin structure and HMGA1 is a well-established histone H1 competitor, we correlated HMGA1 expression and cellular stiffness with histone H1 expression level, post-translational modifications, and nuclear distribution. Our results showed that HMGA1 expression level correlates with nuclear stiffness, is associated to histone H1 phosphorylation status, and alters both histone H1 chromatin distribution and expression. These data suggest that HMGA1 might promote chromatin relaxation through a histone H1-mediated mechanism strongly impacting on the invasiveness of cancer cells-openopenSenigagliesi B, Penzo C, Severino LU, Maraspini R, Petrosino S, Morales-Navarrete H, Pobega E, Ambrosetti E, Parisse P, Pegoraro S, Manfioletti G, Casalis L, Sgarra RSenigagliesi, Beatrice; Penzo, C; Severino, Lu; Maraspini, R; Petrosino, Sara; Morales-Navarrete, H; Pobega, E; Ambrosetti, E; Parisse, P; Pegoraro, S; Manfioletti, G; Casalis, L; Sgarra,

Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads

Lumen morphogenesis results from the interplay between molecular pathways and mechanical forces. In several organs, epithelial cells share their apical surfaces to form a tubular lumen. In the liver, however, hepatocytes share the apical surface only between adjacent cells and form narrow lumina that grow anisotropically, generating a 3D network of bile canaliculi (BC). Here, by studying lumenogenesis in differentiating mouse hepatoblasts in vitro, we discovered that adjacent hepatocytes assemble a pattern of specific extensions of the apical membrane traversing the lumen and ensuring its anisotropic expansion. These previously unrecognized structures form a pattern, reminiscent of the bulkheads of boats, also present in the developing and adult liver. Silencing of Rab35 resulted in loss of apical bulkheads and lumen anisotropy, leading to cyst formation. Strikingly, we could reengineer hepatocyte polarity in embryonic liver tissue, converting BC into epithelial tubes. Our results suggest that apical bulkheads are cell-intrinsic anisotropic mechanical elements that determine the elongation of BC during liver tissue morphogenesis

Role of the employment status and education of mothers in the prevalence of intestinal parasitic infections in Mexican rural schoolchildren

<p><b>Background:</b> Intestinal parasitic infections are a public health problem in developing countries such as Mexico. As a result, two governmental programmes have been implemented: a) "National Deworming Campaign" and b) "Opportunities" aimed at maternal care. However, both programmes are developed separately and their impact is still unknown. We independently investigated whether a variety of socio-economic factors, including maternal education and employment levels, were associated with intestinal parasite infection in rural school children.</p> <p><b>Methods:</b> This cross-sectional study was conducted in 12 rural communities in two Mexican states. The study sites and populations were selected on the basis of the following traits: a) presence of activities by the national administration of albendazole, b) high rates of intestinal parasitism, c) little access to medical examination, and d) a population having less than 2,500 inhabitants. A total of 507 schoolchildren (mean age 8.2 years) were recruited and 1,521 stool samples collected (3 per child). Socio-economic information was obtained by an oral questionnaire. Regression modelling was used to determine the association of socio-economic indicators and intestinal parasitism.</p> <p><b>Results:</b> More than half of the schoolchildren showed poliparasitism (52%) and protozoan infections (65%). The prevalence of helminth infections was higher in children from Oaxaca (53%) than in those from Sinaloa (33%) (p < 0.0001). Giardia duodenalis and Hymenolepis nana showed a high prevalence in both states. Ascaris lumbricoides, Trichuris trichiura and Entamoeba hystolitica/dispar showed low prevalence. Children from lower-income families and with unemployed and less educated mothers showed higher risk of intestinal parasitism (odds ratio (OR) 6.0, 95% confidence interval (CI) 1.6–22.6; OR 4.5, 95% CI 2.5–8.2; OR 3.3, 95% CI 1.5–7.4 respectively). Defecation in open areas was also a high risk factor for infection (OR 2.4, 95% CI 2.0–3.0).</p> <p><b>Conclusion:</b> Intestinal parasitism remains an important public health problem in Sinaloa (north-western Mexico) and Oaxaca (south-eastern Mexico). Lower income, defecation in open areas, employment status and a lower education level of mothers were the significant factors related to these infections. We conclude that mothers should be involved in health initiatives to control intestinal parasitism in Mexico.</p&gt

Trends in eczema prevalence in children and adolescents: A Global Asthma Network Phase I Study

Background: Eczema (atopic dermatitis) is a major global public health issue with high prevalence and morbidity. Our goal was to evaluate eczema prevalence over time, using standardized methodology. Methods: The Global Asthma Network (GAN) Phase I study is an international collaborative study arising from the International Study of Asthma and Allergies in Children (ISAAC). Using surveys, we assessed eczema prevalence, severity, and lifetime prevalence, in global centres participating in GAN Phase I (2015–2020) and one/ both of ISAAC Phase I (1993–1995) and Phase III (2001–2003). We fitted linear mixed models to estimate 10-yearly prevalence trends, by age group, income, and region. Results: We analysed GAN Phase I data from 27 centres in 14 countries involving 74,361 adolescents aged 13–14 and 47,907 children aged 6–7 (response rate 90%, 79%). A median of 6% of children and adolescents had symptoms of current eczema, with 1.1% and 0.6% in adolescents and children, respectively, reporting symptoms of severe eczema. Over 27 years, after adjusting for world region and income, we estimated small overall 10-year increases in current eczema prevalence (adolescents: 0.98%, 95% CI 0.04%–1.92%; children: 1.21%, 95% CI 0.18%–2.24%), and severe eczema (adolescents: 0.26%, 95% CI 0.06%–0.46%; children: 0.23%, 95% CI 0.02%–0.45%) with larger increases in lifetime prevalence (adolescents: 2.71%, 95% CI 1.10%–4.32%; children: 3.91%, 95% CI 2.07%–5.75%). There was substantial heterogeneity in 10-year change between centres (standard deviations 2.40%, 0.58%, and 3.04%), and strong evidence that some of this heterogeneity was explained by region and income level, with increases in some outcomes in high-income children and middle-income adolescents. Conclusions: There is substantial variation in changes in eczema prevalence over time by income and region. Understanding reasons for increases in some regions and decreases in others will help inform prevention strategies

Cadophora margaritata sp. nov. and other fungi associated with the longhorn beetles Anoplophora glabripennis and Saperda carcharias in Finland

Symbiosis with microbes is crucial for survival and development of wood-inhabiting longhorn beetles (Coleoptera: Cerambycidae). Thus, knowledge of the endemic fungal associates of insects would facilitate risk assessment in cases where a new invasive pest occupies the same ecological niche. However, the diversity of fungi associated with insects remains poorly understood. The aim of this study was to investigate fungi associated with the native large poplar longhorn beetle (Saperda carcharias) and the recently introduced Asian longhorn beetle (Anoplophora glabripennis) infesting hardwood trees in Finland. We studied the cultivable fungal associates obtained from Populus tremula colonised by S. carcharias, and Betula pendula and Salix caprea infested by A. glabripennis, and compared these to the samples collected from intact wood material. This study detected a number of plant pathogenic and saprotrophic fungi, and species with known potential for enzymatic degradation of wood components. Phylogenetic analyses of the most commonly encountered fungi isolated from the longhorn beetles revealed an association with fungi residing in the Cadophora-Mollisia species complex. A commonly encountered fungus was Cadophora spadicis, a recently described fungus associated with wood-decay. In addition, a novel species of Cadophora, for which the name Cadophora margaritata sp. nov. is provided, was isolated from the colonised wood.Peer reviewe

Worldwide trends in the burden of asthma symptoms in school-aged children: Global Asthma Network Phase I cross-sectional study

Background: Asthma is the most common chronic disease in children globally. The Global Asthma Network (GAN) Phase I study aimed to determine if the worldwide burden of asthma symptoms is changing. Methods: This updated cross-sectional study used the same methods as the International study of Asthma and Allergies in Childhood (ISAAC) Phase III. Asthma symptoms were assessed from centres that completed GAN Phase I and ISAAC Phase I (1993–95), ISAAC Phase III (2001–03), or both. We included individuals from two age groups (children aged 6–7 years and adolescents aged 13–14 years) who self-completed written questionnaires at school. We estimated the 10-year rate of change in prevalence of current wheeze, severe asthma symptoms, ever having asthma, exercise wheeze, and night cough (defined by core questions in the questionnaire) for each centre, and we estimated trends across world regions and income levels using mixed-effects linear regression models with region and country income level as confounders. Findings: Overall, 119 795 participants from 27 centres in 14 countries were included: 74 361 adolescents (response rate 90%) and 45 434 children (response rate 79%). About one in ten individuals of both age groups had wheeze in the preceding year, of whom almost half had severe symptoms. Most centres showed a change in prevalence of 2 SE or more between ISAAC Phase III to GAN Phase I. Over the 27-year period (1993–2020), adolescents showed a significant decrease in percentage point prevalence per decade in severe asthma symptoms (–0·37, 95% CI –0·69 to –0·04) and an increase in ever having asthma (1·25, 0·67 to 1·83) and night cough (4·25, 3·06 to 5·44), which was also found in children (3·21, 1·80 to 4·62). The prevalence of current wheeze decreased in low-income countries (–1·37, –2·47 to –0·27], in children and –1·67, –2·70 to –0·64, in adolescents) and increased in lower-middle-income countries (1·99, 0·33 to 3·66, in children and 1·69, 0·13 to 3·25, in adolescents), but it was stable in upper-middle-income and high-income countries. Interpretation: Trends in prevalence and severity of asthma symptoms over the past three decades varied by age group, country income, region, and centre. The high worldwide burden of severe asthma symptoms would be mitigated by enabling access to effective therapies for asthma. Funding: International Union Against Tuberculosis and Lung Disease, Boehringer Ingelheim New Zealand, AstraZeneca Educational Grant, National Institute for Health Research, UK Medical Research Council, European Research Council, and Instituto de Salud Carlos III

The modulating effect of education on semantic interference during healthy aging

Aging has traditionally been related to impairments in name retrieval. These impairments have usually been explained by a phonological transmission deficit hypothesis or by an inhibitory deficit hypothesis. This decline can, however, be modulated by the educational level of the sample. This study analyzed the possible role of these approaches in explaining both object and face naming impairments during aging. Older adults with low and high educational level and young adults with high educational level were asked to repeatedly name objects or famous people using the semantic-blocking paradigm. We compared naming when exemplars were presented in a semantically homogeneous or in a semantically heterogeneous context. Results revealed significantly slower rates of both face and object naming in the homogeneous context (i.e., semantic interference), with a stronger effect for face naming. Interestingly, the group of older adults with a lower educational level showed an increased semantic interference effect during face naming. These findings suggest the joint work of the two mechanisms proposed to explain age-related naming difficulties, i.e., the inhibitory deficit and the transmission deficit hypothesis. Therefore, the stronger vulnerability to semantic interference in the lower educated older adult sample would possibly point to a failure in the inhibitory mechanisms in charge of interference resolution, as proposed by the inhibitory deficit hypothesis. In addition, the fact that this interference effect was mainly restricted to face naming and not to object naming would be consistent with the increased age-related difficulties during proper name retrieval, as suggested by the transmission deficit hypothesis.This research was supported by grants PSI2013-46033-P to A.M., PSI2015-65502-C2-1-P to M.T.B., PCIN-2015-165-C02-01 to D.P., PSI2017-89324-C2-1-P to DP from the Spanish Ministry of Economy and Competitiveness (http://www.mineco.gob.es/)

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015