Graph theoretic network analysis reveals protein pathways underlying cell death following neurotropic viral infection

Complex protein networks underlie any cellular function. Certain proteins play a pivotal role in many network configurations, disruption of whose expression proves fatal to the cell. An efficient method to tease out such key proteins in a network is still unavailable. Here, we used graph-theoretic measures on protein-protein interaction data (interactome) to extract biophysically relevant information about individual protein regulation and network properties such as formation of function specific modules (sub-networks) of proteins. We took 5 major proteins that are involved in neuronal apoptosis post Chandipura Virus (CHPV) infection as seed proteins in a database to create a meta-network of immediately interacting proteins (1st order network). Graph theoretic measures were employed to rank the proteins in terms of their connectivity and the degree upto which they can be organized into smaller modules (hubs). We repeated the analysis on 2nd order interactome that includes proteins connected directly with proteins of 1st order. FADD and Casp-3 were connected maximally to other proteins in both analyses, thus indicating their importance in neuronal apoptosis. Thus, our analysis provides a blueprint for the detection and validation of protein networks disrupted by viral infections

Dysregulation in Subcellular Localization of Myelin Basic Protein mRNA Does Not Result in Altered Myelination in Amyotrophic Lateral Sclerosis

Pathological hallmarks of amyotrophic lateral sclerosis (ALS), including protein misfolding, are well established in oligodendrocytes. More recently, an RNA trafficking deficit of key myelin proteins has been suggested in oligodendrocytes in ALS but the extent to which this affects myelination and the relative contribution of this to disease pathogenesis is unclear. ALS autopsy research findings showing demyelination contrasts with the routine clinical-pathological workup of ALS cases where it is rare to see white matter abnormalities other than simple Wallerian degeneration secondary to widespread neuronal loss. To begin to address this apparent variance, we undertook a comprehensive evaluation of myelination at an RNA, protein and structural level using human pathological material from sporadic ALS patients, genetic ALS patients (harboring C9orf72 mutation) and age- and sex-matched non-neurological controls. We performed (i) quantitative spatial profiling of the mRNA transcript encoding myelin basic protein (MBP), (ii) quantification of MBP protein and (iii) the first quantitative structural assessment of myelination in ALS post-mortem specimens by electron microscopy. We show no differences in MBP protein levels or ultrastructural myelination, despite a significant dysregulation in the subcellular trafficking of MBP mRNA in ALS patients compared to controls. We therefore confirm that whilst there are cell autonomous mRNA trafficking deficits affecting oligodendrocytes in ALS, this has no effect on myelin structure

Dysregulation in Subcellular Localization of Myelin Basic Protein mRNA Does Not Result in Altered Myelination in Amyotrophic Lateral Sclerosis

Pathological hallmarks of amyotrophic lateral sclerosis (ALS), including protein misfolding, are well established in oligodendrocytes. More recently, an RNA trafficking deficit of key myelin proteins has been suggested in oligodendrocytes in ALS but the extent to which this affects myelination and the relative contribution of this to disease pathogenesis is unclear. ALS autopsy research findings showing demyelination contrasts with the routine clinical-pathological workup of ALS cases where it is rare to see white matter abnormalities other than simple Wallerian degeneration secondary to widespread neuronal loss. To begin to address this apparent variance, we undertook a comprehensive evaluation of myelination at an RNA, protein and structural level using human pathological material from sporadic ALS patients, genetic ALS patients (harboring C9orf72 mutation) and age- and sex-matched non-neurological controls. We performed (i) quantitative spatial profiling of the mRNA transcript encoding myelin basic protein (MBP), (ii) quantification of MBP protein and (iii) the first quantitative structural assessment of myelination in ALS post-mortem specimens by electron microscopy. We show no differences in MBP protein levels or ultrastructural myelination, despite a significant dysregulation in the subcellular trafficking of MBP mRNA in ALS patients compared to controls. We therefore confirm that whilst there are cell autonomous mRNA trafficking deficits affecting oligodendrocytes in ALS, this has no effect on myelin structure.</p

Environmental filtering controls soil biodiversity in wet tropical ecosystems

9 páginas..- 4 figuras.- referencias.- Supplementary data to this article can be found online at https://doi. org/10.1016/j.soilbio.2022.108571The environmental factors controlling soil biodiversity along resource gradients remain poorly understood in wet tropical ecosystems. Aboveground biodiversity is expected to be driven by changes in nutrient availability in these ecosystems, however, much less is known about the importance of nutrient availability in driving soil biodiversity. Here, we combined a cross-continental soil survey across tropical regions with a three decades' field experiment adding nitrogen (N) and phosphorus (P) (100 kg N ha(-1)y(-1) and 100 kg P ha(-1)y(-1)) to Hawai'ian tropical forests with contrasting substrate ages (300 and 4,100,000 years) to investigate the influence of nutrient availability to explain the biodiversity of soil bacteria, fungi, protists, invertebrates and key functional genes. We found that soil biodiversity was driven by soil acidification during long-term pedogenesis and across environmental gradients, rather than by nutrient limitations. In fact, our results showed that experimental N additions caused substantial acidification in soils from Hawai'i. These declines in pH were related to large decreases in soil biodiversity from tropical ecosystems in four continents. Moreover, the microbial activity did not change in response to long-term N and P additions. We concluded that environmental filtering drives the biodiversity of multiple soil organisms, and that the acidification effects associated with N additions can further create substantial undesired net negative effects on overall soil biodiversity in naturally tropical acid soils. This knowledge is integral for the understanding and management of soil biodiversity in tropical ecosystems globally.Supported by a Ramón y Cajal grant (RYC2018-025483-I), a “Ayuda P.P. 2020. Desarrollo Lineas Investigación Propias (UPO), a project from the Spanish Ministry of Science and Innovation (PID2020-115813RA-I00), and a project PAIDI 2020 from the Junta de Andalucía (P20_00879). H.Y.C. is supported by National Natural Science Foundation of China (32101335), China Postdoctoral Science Foundation (2021M690589), Innovation Project of Young Technological Talents in Changchun City (21QC07), and Fundamental Research Funds for the Central Universities (2412021QD014). J.P.V. is thankful to DST and SERB (Science and Engineering Research Board), India for financial support for plant-microbe interaction research. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government.Peer reviewe

Imaging of bronchial pathology in antibody deficiency: Data from the European Chest CT Group

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease

Global hotspots for soil nature conservation

19 páginas.- 5 figuras.- 98 referencias.- Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41586-022-05292-xSoils are the foundation of all terrestrial ecosystems1. However, unlike for plants and animals, a global assessment of hotspots for soil nature conservation is still lacking2. This hampers our ability to establish nature conservation priorities for the multiple dimensions that support the soil system: from soil biodiversity to ecosystem services. Here, to identify global hotspots for soil nature conservation, we performed a global field survey that includes observations of biodiversity (archaea, bacteria, fungi, protists and invertebrates) and functions (critical for six ecosystem services) in 615 composite samples of topsoil from a standardized survey in all continents. We found that each of the different ecological dimensions of soils—that is, species richness (alpha diversity, measured as amplicon sequence variants), community dissimilarity and ecosystem services—peaked in contrasting regions of the planet, and were associated with different environmental factors. Temperate ecosystems showed the highest species richness, whereas community dissimilarity peaked in the tropics, and colder high-latitudinal ecosystems were identified as hotspots of ecosystem services. These findings highlight the complexities that are involved in simultaneously protecting multiple ecological dimensions of soil. We further show that most of these hotspots are not adequately covered by protected areas (more than 70%), and are vulnerable in the context of several scenarios of global change. Our global estimation of priorities for soil nature conservation highlights the importance of accounting for the multidimensionality of soil biodiversity and ecosystem services to conserve soils for future generations.This project received funding from the British Ecological Society (agreement LRA17\1193; MUSGONET). C.A.G. and N.E. were funded by DFG–FZT 118, 202548816; C.A.G. was supported by FCT-PTDC/BIA-CBI/2340/2020; M.D.-B. was supported by RYC2018-025483-I, PID2020-115813RA-I00\MCIN/AEI/10.13039/501100011033 and P20_00879. M.A.M.-M. and S.A. were funded by FONDECYT 1181034 and ANID-PIA-Anillo INACH ACT192057. J.D. and A.R. acknowledge support from IF/00950/2014, 2020.03670.CEECIND, SFRH/BDP/108913/2015 and UIDB/04004/2020. Y.-R.L. was supported by 2662019PY010 from the FRFCU. L.T. was supported by the ESF grant PRG632. F.B. and J.L.M. were supported by i-LINK+2018 (LINKA20069) funded by CSIC. C.T.-D. was supported by the Grupo de Biodibersidad & Cambio Global UBB–GI 170509/EF. C.P. was supported by the EU H2020 grant agreement 101000224. H.C. was supported by NSFC32101335, FRFCU2412021QD014 and CPSF2021M690589. J.P.V. was supported by DST (DST/INT/SL/P-31/2021) SERB (EEQ/2021/001083) and BHU-IoE (6031).Peer reviewe

Publisher Correction: Soil contamination in nearby natural areas mirrors that in urban greenspaces worldwide

Correction to: Nature Communications, published online 27 March 2023 In the version of this article originally published, the current affiliation 25, “CEAZA, Universidad Católica del Norte, Coquimbo, Chile,” initially appeared as the last affiliation, offsetting all author footnotes from 25-39. The affiliation order has been restored in the article.Peer reviewe