Predicting collapse of adaptive networked systems without knowing the network

The collapse of ecosystems, the extinction of species, and the breakdown of economic and financial networks usually hinges on topological properties of the underlying networks, such as the existence of self-sustaining (or autocatalytic) feedback cycles. Such collapses can be understood as a massive change of network topology, usually accompanied by the extinction of a macroscopic fraction of nodes and links. It is often related to the breakdown of the last relevant directed catalytic cycle within a dynamical system. Without detailed structural information it seems impossible to state, whether a network is robust or if it is likely to collapse in the near future. Here we show that it is nevertheless possible to predict collapse for a large class of systems that are governed by a linear (or linearized) dynamics. To compute the corresponding early warning signal, we require only non-structural information about the nodes’ states such as species abundances in ecosystems, or company revenues in economic networks. It is shown that the existence of a single directed cycle in the network can be detected by a “quantization effect” of node states, that exists as a direct consequence of a corollary of the Perron–Frobenius theorem. The proposed early warning signal for the collapse of networked systems captures their structural instability without relying on structural information. We illustrate the validity of the approach in a transparent model of co-evolutionary ecosystems and show this quantization in systems of species evolution, epidemiology, and population dynamics

ElaD, a Deubiquitinating Protease Expressed by E. Coli

Background: Ubiquitin and ubiquitin-like proteins (Ubl) are designed to modify polypeptides in eukaryotes. Covalent binding of ubiquitin or Ubls to substrate proteins can be reversed by specific hydrolases. One particular set of cysteine proteases, the CE clan, which targets ubiquitin and Ubls, has homologs in eukaryotes, prokaryotes, and viruses. Findings: We have cloned and analyzed the E. coli protein elaD, which is distantly related to eukaryotic CE clan members of the ULP/SENP protease family that are specific for SUMO and Nedd8. Previously misannotated as a putative sulfatase/phosphatase, elaD is an efficient and specific deubiquitinating enzyme in vitro. Interestingly, elaD is present in all intestinal pathogenic E. coli strains, but conspicuously absent from extraintestinal pathogenic strains (ExPECs). Further homologs of this protease can be found in Acanthamoeba Polyphaga Mimivirus, and in Alpha-, Beta-and Gammaproteobacteria. Conclusion: The expression of ULP/SENP-related hydrolases in bacteria therefore extends to plant pathogens and medically relevant strains of Escherichia coli, Legionella pneumophila, Rickettsiae, Chlamydiae, and Salmonellae, in which the elaD ortholog sseL has recently been identified as a virulence factor with deubiquitinating activity. As a counterpoint, our phylogenetic and functional examination reveals that ancient eukaryotic ULP/SENP proteases also have the potential of ubiquitin-specific hydrolysis, suggesting an early common origin of this peptidase clan

Screen for ISG15-crossreactive Deubiquitinases

Background: The family of ubiquitin-like molecules (UbLs) comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin. ISG15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type I interferon. ISG15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors. Specific proteases are able to reverse modification with ubiquitin or UbLs by hydrolyzing the covalent bond between their C-termini and substrate proteins. The tail regions of ubiquitin and ISG15 are identical and we therefore hypothesized that promiscuous deubiquitinating proteases (DUBs) might exist, capable of recognizing both ubiquitin and ISG15. Results: We have cloned and expressed 22 human DUBs, representing the major clades of the USP protease family. Utilizing suicide inhibitors based on ubiquitin and ISG15, we have identified USP2, USP5 (IsoT1), USP13 (IsoT3), and USP14 as ISG15-reactive proteases, in addition to the bona fide ISG15-specific protease USP18 (UBP43). USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome. Conclusions: By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin. Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 null mice

A dynamical approach to the spatiotemporal aspects of the Portevin-Le Chatelier effect: Chaos,turbulence and band propagation

Experimental time series obtained from single and poly-crystals subjected to a constant strain rate tests report an intriguing dynamical crossover from a low dimensional chaotic state at medium strain rates to an infinite dimensional power law state of stress drops at high strain rates. We present results of an extensive study of all aspects of the PLC effect within the context a model that reproduces this crossover. A study of the distribution of the Lyapunov exponents as a function of strain rate shows that it changes from a small set of positive exponents in the chaotic regime to a dense set of null exponents in the scaling regime. As the latter feature is similar to the GOY shell model for turbulence, we compare our results with the GOY model. Interestingly, the null exponents in our model themselves obey a power law. The configuration of dislocations is visualized through the slow manifold analysis. This shows that while a large proportion of dislocations are in the pinned state in the chaotic regime, most of them are at the threshold of unpinning in the scaling regime. The model qualitatively reproduces the different types of deformation bands seen in experiments. At high strain rates where propagating bands are seen, the model equations are reduced to the Fisher-Kolmogorov equation for propagative fronts. This shows that the velocity of the bands varies linearly with the strain rate and inversely with the dislocation density, consistent with the known experimental results. Thus, this simple dynamical model captures the complex spatio-temporal features of the PLC effect.Comment: 17 pages, 18 figure

Screen for ISG15-crossreactive deubiquitinases

Background. The family of ubiquitin-like molecules (UbLs) comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin. ISG15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type I interferon. ISG15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors. Specific proteases are able to reverse modification with ubiquitin or UbLs by hydrolyzing the covalent bond between their C-termini and substrate proteins. The tail regions of ubiquitin and ISG15 are identical and we therefore hypothesized that promiscuous deubiquitinating proteases (DUBs) might exist, capable of recognizing both ubiquitin and ISG15. Results. We have cloned and expressed 22 human DUBs, representing the major clades of the USP protease family. Utilizing suicide inhibitors based on ubiquitin and ISG15, we have identified USP2, USP5 (IsoT1), USP13 (IsoT3), and USP14 as ISG15-reactive proteases, in addition to the bona fide ISG15-specific protease USP18 (UBP43). USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome. Conclusions. By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin. Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 null mice. Citation: Catic A, Fiebiger E, Korbel GA, Blom D, Galardy PJ, et al (2007) Screen for ISG15-crossreactive Deubiquitinases. PLoS ONE 2(7): e679

Invertebrate traits, diversity and the vulnerability of groundwater ecosystems

Funding Information: This manuscript evolved from a workshop titled Trait‐based analyses in groundwater ecology and bioassessment held as part of the 24th International Conference on Subterranean Biology, 20–24th August 2018, University of Aveiro, Portugal. The workshop was supported by the conference organisers and the Macquarie University Species Spectrum Research Centre. Financial support was also provided to M.A.D. by the Portuguese government (Fundação para a Ciência e Tecnologia; FCT) through the research unit UIDB/04085/2020 (CENSE). A.S.P.S.R. was supported by the VILLUM FONDEN (research grant 15471) and by Portuguese National Funds through Fundação para a Ciência e a Tecnologia within the cE3c Unit funding UIDB/00329/2020. S.I.S. acknowledges funding through EU Operational Programme Research, Development and Education No. CZ.02.2.69/0.0/0.0/16_027/0008357, and by the Ministry of Education, Youth and Sports of the Czech Republic [grant number CZ.02.1.01/0.0/0.0/16 025/0007417]. K.L.K. was supported in part by Australian Research Council grant LP190100927. The comments of the Editor, Associate Editor and an anonymous reviewer greatly improved the MS. Open access publishing facilitated by Macquarie University, as part of the Wiley ‐ Macquarie University agreement via the Council of Australian University Librarians. Publisher Copyright: © 2022 The Authors. Functional Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.Groundwater comprises the largest freshwater ecosystem on the planet. It has a distinct regime of extreme, yet stable environmental conditions that have favoured the development of similar morphological and functional traits in the resident invertebrate fauna (stygofauna). The analysis of community traits is increasingly used as an alternative to taxonomy-based assessments of biodiversity, especially for monitoring ecosystem status and linking the functions of organisms to ecological processes, yet it has been rarely applied to stygofauna and groundwater ecosystems. In this paper, we review the variation in functional traits among the invertebrate fauna of this important ecosystem. We focus on the stygofauna and processes of alluvium and fractured rock aquifers that are typified by small voids and fissures that constrain the habitats and environmental conditions. As a first step, we compare trait variability between groundwater and surface water invertebrate communities and then examine the significance of the ranges of these traits to the vulnerability of the ecosystem to change. Fifteen potentially useful functional traits are recognised. Eight of these have narrower ranges (i.e. exhibit fewer states, or attributes, of a particular trait) in groundwater than they do in surface water. Two traits have wider ranges. Our synthesis suggests that the relative stability of groundwater environments has led to low trait variability. The low biomass and low reproductive rate of stygofauna suggest that recovery potential following disturbance is likely to be low. For the purposes of both improved understanding and effective management, further work is needed to document additional functional traits and their states in groundwater fauna, enabling a better understanding of the relationship between response and effect traits in these ecosystems. Read the free Plain Language Summary for this article on the Journal blog.publishersversionpublishe

High-Resolution Copy-Number Variation Map Reflects Human Olfactory Receptor Diversity and Evolution

Olfactory receptors (ORs), which are involved in odorant recognition, form the largest mammalian protein superfamily. The genomic content of OR genes is considerably reduced in humans, as reflected by the relatively small repertoire size and the high fraction (∼55%) of human pseudogenes. Since several recent low-resolution surveys suggested that OR genomic loci are frequently affected by copy-number variants (CNVs), we hypothesized that CNVs may play an important role in the evolution of the human olfactory repertoire. We used high-resolution oligonucleotide tiling microarrays to detect CNVs across 851 OR gene and pseudogene loci. Examining genomic DNA from 25 individuals with ancestry from three populations, we identified 93 OR gene loci and 151 pseudogene loci affected by CNVs, generating a mosaic of OR dosages across persons. Our data suggest that ∼50% of the CNVs involve more than one OR, with the largest CNV spanning 11 loci. In contrast to earlier reports, we observe that CNVs are more frequent among OR pseudogenes than among intact genes, presumably due to both selective constraints and CNV formation biases. Furthermore, our results show an enrichment of CNVs among ORs with a close human paralog or lacking a one-to-one ortholog in chimpanzee. Interestingly, among the latter we observed an enrichment in CNV losses over gains, a finding potentially related to the known diminution of the human OR repertoire. Quantitative PCR experiments performed for 122 sampled ORs agreed well with the microarray results and uncovered 23 additional CNVs. Importantly, these experiments allowed us to uncover nine common deletion alleles that affect 15 OR genes and five pseudogenes. Comparison to the chimpanzee reference genome revealed that all of the deletion alleles are human derived, therefore indicating a profound effect of human-specific deletions on the individual OR gene content. Furthermore, these deletion alleles may be used in future genetic association studies of olfactory inter-individual differences

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Systematic Inference of Copy-Number Genotypes from Personal Genome Sequencing Data Reveals Extensive Olfactory Receptor Gene Content Diversity

Copy-number variations (CNVs) are widespread in the human genome, but comprehensive assignments of integer locus copy-numbers (i.e., copy-number genotypes) that, for example, enable discrimination of homozygous from heterozygous CNVs, have remained challenging. Here we present CopySeq, a novel computational approach with an underlying statistical framework that analyzes the depth-of-coverage of high-throughput DNA sequencing reads, and can incorporate paired-end and breakpoint junction analysis based CNV-analysis approaches, to infer locus copy-number genotypes. We benchmarked CopySeq by genotyping 500 chromosome 1 CNV regions in 150 personal genomes sequenced at low-coverage. The assessed copy-number genotypes were highly concordant with our performed qPCR experiments (Pearson correlation coefficient 0.94), and with the published results of two microarray platforms (95–99% concordance). We further demonstrated the utility of CopySeq for analyzing gene regions enriched for segmental duplications by comprehensively inferring copy-number genotypes in the CNV-enriched >800 olfactory receptor (OR) human gene and pseudogene loci. CopySeq revealed that OR loci display an extensive range of locus copy-numbers across individuals, with zero to two copies in some OR loci, and two to nine copies in others. Among genetic variants affecting OR loci we identified deleterious variants including CNVs and SNPs affecting ∼15% and ∼20% of the human OR gene repertoire, respectively, implying that genetic variants with a possible impact on smell perception are widespread. Finally, we found that for several OR loci the reference genome appears to represent a minor-frequency variant, implying a necessary revision of the OR repertoire for future functional studies. CopySeq can ascertain genomic structural variation in specific gene families as well as at a genome-wide scale, where it may enable the quantitative evaluation of CNVs in genome-wide association studies involving high-throughput sequencing

Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.

Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity