Project description:Bacterial infections can be aggravated by antibiotic treatment that induces SOS response and vesiculation. This leads to a hypothesis concerning association of SOS with vesiculation. To test it, we conducted multiple analyses of outer membrane vesicles (OMVs) produced from the Pseudomonas aeruginosa wild type in which SOS is induced by ciprofloxacin and from the LexA noncleavable (lexAN) strain in which SOS is repressed. The levels of OMV proteins, lipids, and cytotoxicity increased for both the treated strains, demonstrating vesiculation stimulation by the antibiotic treatment. However, the further increase was suppressed in the lexAN strains, suggesting the SOS involvement. Obviously, the stimulated vesiculation is attributed by both SOS-related and unrelated factors. OMV subproteomic analysis was performed to examine these factors, which reflected the OMV-mediated cytotoxicity and the physiology of the vesiculating cells under treatment and SOS. Thus, SOS plays a role in the vesiculation stimulation that contributes to cytotoxicity.
Project description:This study builds conceptual explanations and empirical examinations of the vulnerability response of networks under attack. Two quantities of "vulnerability" and "uncertainty in vulnerability" are defined by scrutinizing the performance loss trajectory of networks experiencing attacks. Both vulnerability and uncertainty in vulnerability quantities are a function of the network topology and size. This is tested on 16 distinct topologies appearing in infrastructure, social, and biological networks with 8 to 26 nodes under two percolation scenarios exemplifying benign and malicious attacks. The findings imply (i) crossing path, tree, and diverging tail are the most vulnerable topologies, (ii) complete and matching pairs are the least vulnerable topologies, (iii) complete grid and complete topologies show the most uncertainty for vulnerability, and (iv) hub-and-spoke and double u exhibit the least uncertainty in vulnerability. The findings also imply that both vulnerability and uncertainty in vulnerability increase with an increase in the size of the network. It is argued that in networks with no undirected cycle and one undirected cycle, the uncertainty in vulnerability is maximal earlier in the percolation process. With an increase in the number of cycles, the uncertainty in vulnerability is accumulated at the end of the percolation process. This emphasizes the role of tailoring preparedness, response, and recovery phases for networks with different topologies when they might experience disruption.
Project description:Taxonomy is essential to biological sciences and the priority field in face of the biodiversity crisis. The industry of scientific publications has made extensive promotion and display of bibliometric indexes, resulting in side effects such as the Journal Impact Factor™ (JIF) mania. Inadequacies of the widely used indexes to assess taxonomic publications are among the impediments for the progress of this field. Based on an unusually high proportion of self-citations, the mega-journal Zootaxa, focused on zoological taxonomy, was suppressed from the Journal Citation Reports (JCR, Clarivate™). A prompt reaction from the scientific community against this decision took place exposing myths and misuses of bibliometrics. Our goal is to shed light on the impact of misuse of bibliometrics to the production in taxonomy. We explored JCR's metrics for 2010-2018 of 123 zoological journals publishing taxonomic studies. Zootaxa, with around 15 000 citations, received 311% more citations than the second most cited journal, and shows higher levels of self-citations than similar journals. We consider Zootaxa's scope and the fact that it is a mega-journal are insufficient to explain its high level of self-citation. Instead, this result is related to the 'Zootaxa phenomenon', a sociological bias that includes visibility and potentially harmful misconceptions that portray the journal as the only one that publishes taxonomic studies. Menaces to taxonomy come from many sources and the low bibliometric indexes, including JIF, are only one factor among a range of threats. Instead of being focused on statistically illiterate journal metrics endorsing the villainy of policies imposed by profit-motivated companies, taxonomists should be engaged with renewed strength in actions directly connected to the promotion and practice of this science without regard for citation analysis.
Project description:Centronuclear myopathies are a group of congenital myopathies characterized by severe muscle weakness, genetic heterogeneity, and defects in the structural organization of muscle fibers. Their names are derived from the central position of nuclei on biopsies, while they are at the fiber periphery under normal conditions. No specific therapy exists yet for these debilitating diseases. Mutations in the myotubularin phosphoinositides phosphatase, the GTPase dynamin 2, or amphiphysin 2 have been identified to cause respectively X-linked centronuclear myopathies (also called myotubular myopathy) or autosomal dominant and recessive forms. Mutations in additional genes, as RYR1, TTN, SPEG or CACNA1S, were linked to phenotypes that can overlap with centronuclear myopathies. Numerous animal models of centronuclear myopathies have been studied over the last 15 years, ranging from invertebrate to large mammalian models. Their characterization led to a partial understanding of the pathomechanisms of these diseases and allowed the recent validation of therapeutic proof-of-concepts. Here, we review the different therapeutic strategies that have been tested so far for centronuclear myopathies, some of which may be translated to patients.
Project description:We introduce a compartmental model with age structure to study the dynamics of the SARS-COV-2 pandemic. The contagion matrix in the model is given by the product of a probability per contact with a contact matrix explicitly taking into account the contact structure among different age groups. The probability of contagion per contact is considered as time dependent to represent non-pharmaceutical interventions, and is fitted from the time series of deaths. The approach is used to study the evolution of the COVID-19 pandemic in the main Brazilian cities and compared to two good quality serological surveys. We also discuss with some detail the case of the city of Manaus which raised special attention due to a previous report of three-quarters attack rate by the end of 2020. We discuss estimates for Manaus and all Brazilian cities with a total population of more than one million. We also estimate the attack rate with respect to the total population, in each Brazilian state by January, 1 st 2021 and May, 23 2021.
Project description:From transportation networks to complex infrastructures, and to social and economic networks, a large variety of systems can be described in terms of multiplex networks formed by a set of nodes interacting through different network layers. Network robustness, as one of the most successful application areas of complex networks, has attracted great interest in a myriad of research realms. In this regard, how multiplex networks respond to potential attack is still an open issue. Here we study the robustness of multiplex networks under layer node-based random or targeted attack, which means that nodes just suffer attacks in a given layer yet no additional influence to their connections beyond this layer. A theoretical analysis framework is proposed to calculate the critical threshold and the size of giant component of multiplex networks when nodes are removed randomly or intentionally. Via numerous simulations, it is unveiled that the theoretical method can accurately predict the threshold and the size of giant component, irrespective of attack strategies. Moreover, we also compare the robustness of multiplex networks under multiplex node-based attack and layer node-based attack, and find that layer node-based attack makes multiplex networks more vulnerable, regardless of average degree and underlying topology.
Project description:Since plants lack specialized immune cells, each cell has to defend itself independently against a plethora of different pathogens. Therefore, successful plant defense strongly relies on precise and efficient regulation of intracellular processes in every single cell. Smooth trafficking within the plant endomembrane is a prerequisite for a diverse set of immune responses. Pathogen recognition, signaling into the nucleus, cell wall enforcement, secretion of antimicrobial proteins and compounds, as well as generation of reactive oxygen species, all heavily depend on vesicle transport. In contrast, pathogens have developed a variety of different means to manipulate vesicle trafficking to prevent detection or to inhibit specific plant responses. Intriguingly, the plant endomembrane system exhibits remarkable plasticity upon pathogen attack. Unconventional trafficking pathways such as the formation of endoplasmic reticulum (ER) bodies or fusion of the vacuole with the plasma membrane are initiated and enforced as the counteraction. Here, we review the recent findings on unconventional and defense-induced trafficking pathways as the plant´s measures in response to pathogen attack. In addition, we describe the endomembrane system manipulations by different pathogens, with a focus on tethering and fusion events during vesicle trafficking.
Project description:Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under herbivore attack is scarce, especially below ground. Here, we tested whether latex secondary metabolites produced by the common dandelion (Taraxacum officinale agg.) decrease the performance of its major native insect root herbivore, the larvae of the common cockchafer (Melolontha melolontha), and benefit plant vegetative and reproductive fitness under M. melolontha attack. Across 17 T. officinale genotypes screened by gas and liquid chromatography, latex concentrations of the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G) were negatively associated with M. melolontha larval growth. Adding purified TA-G to artificial diet at ecologically relevant concentrations reduced larval feeding. Silencing the germacrene A synthase ToGAS1, an enzyme that was identified to catalyze the first committed step of TA-G biosynthesis, resulted in a 90% reduction of TA-G levels and a pronounced increase in M. melolontha feeding. Transgenic, TA-G-deficient lines were preferred by M. melolontha and suffered three times more root biomass reduction than control lines. In a common garden experiment involving over 2,000 T. officinale individuals belonging to 17 different genotypes, high TA-G concentrations were associated with the maintenance of high vegetative and reproductive fitness under M. melolontha attack. Taken together, our study demonstrates that a latex secondary metabolite benefits plants under herbivore attack, a result that provides a mechanistic framework for root herbivore driven natural selection and evolution of plant defenses below ground.
Project description:UnlabelledThe SOS response is a transcriptional regulatory network governed by the LexA repressor that activates in response to DNA damage. In the Betaproteobacteria, LexA is known to target a palindromic sequence with the consensus sequence CTGT-N8-ACAG. We report the characterization of a LexA regulon in the iron-oxidizing betaproteobacterium Sideroxydans lithotrophicus. In silico and in vitro analyses show that LexA targets six genes by recognizing a binding motif with the consensus sequence GAACGaaCGTTC, which is strongly reminiscent of the Bacillus subtilis LexA-binding motif. We confirm that the closely related Gallionella capsiferriformans shares the same LexA-binding motif, and in silico analyses indicate that this motif is also conserved in the Nitrosomonadales and the Methylophilales. Phylogenetic analysis of LexA and the alpha subunit of DNA polymerase III (DnaE) reveal that the organisms harboring this noncanonical LexA form a compact taxonomic cluster within the Betaproteobacteria. However, their lexA gene is unrelated to the standard Betaproteobacteria lexA, and there is evidence of its spread through lateral gene transfer. In contrast to other reported cases of noncanonical LexA-binding motifs, the regulon of S. lithotrophicus is comparable in size and function to that of many other Betaproteobacteria, suggesting that a convergent SOS regulon has reevolved under the control of a new LexA protein. Analysis of the DNA-binding domain of S. lithotrophicus LexA reveals little sequence similarity with that of other LexA proteins targeting similar binding motifs, suggesting that network structure may limit site evolution or that structural constrains make the B. subtilis-type motif an optimal interface for multiple LexA sequences.ImportanceUnderstanding the evolution of transcriptional systems enables us to address important questions in microbiology, such as the emergence and transfer potential of different regulatory systems to regulate virulence or mediate responses to stress. The results reported here constitute the first characterization of a noncanonical LexA protein regulating a standard SOS regulon. This is significant because it illustrates how a complex transcriptional program can be put under the control of a novel transcriptional regulator. Our results also reveal a substantial degree of plasticity in the LexA recognition domain, raising intriguing questions about the space of protein-DNA interfaces and the specific evolutionary constrains faced by these elements.
Project description:RNA-seq libraries purified from rLCMV-Cre infected neurons using the Ribotag allele. Seq libraries are provided from STAT1 competent (Stat1+/+ x Rpl22HA/+) or STAT1-deficient (Stat1fl/fl x Rpl22HA/+) rLCMV-Cre carrier mice which have been challenged intravenously with LCMVwt at 5 weeks of age and then sacrificed after 9 days. These seq libraries represent the response of rLCMV-Cre infected neurons to CD8+ T cell attack following challenge with LCMVwt.