Irreducible pseudo 2-factor isomorphic cubic bipartite graphs

A bipartite graph is {\em pseudo 2--factor isomorphic} if all its 2--factors have the same parity of number of circuits. In \cite{ADJLS} we proved that the only essentially 4--edge-connected pseudo 2--factor isomorphic cubic bipartite graph of girth 4 is $K_{3,3}$, and conjectured \cite[Conjecture 3.6]{ADJLS} that the only essentially 4--edge-connected cubic bipartite graphs are $K_{3,3}$, the Heawood graph and the Pappus graph. There exists a characterization of symmetric configurations $n_3$ %{\bf decide notation and how to use it in the rest of the paper} due to Martinetti (1886) in which all symmetric configurations $n_3$ can be obtained from an infinite set of so called {\em irreducible} configurations \cite{VM}. The list of irreducible configurations has been completed by Boben \cite{B} in terms of their {\em irreducible Levi graphs}. In this paper we characterize irreducible pseudo 2--factor isomorphic cubic bipartite graphs proving that the only pseudo 2--factor isomorphic irreducible Levi graphs are the Heawood and Pappus graphs. Moreover, the obtained characterization allows us to partially prove the above Conjecture

Single-nucleotide polymorphism-based genetic risk score and patient age at prostate cancer diagnosis

Importance: Few studies have evaluated the association between a single-nucleotide polymorphism-based genetic risk score (GRS) and patient age at prostate cancer (PCa) diagnosis. Objectives: To test the association between a GRS and patient age at PCa diagnosis and to compare the performance of a GRS with that of family history (FH) in PCa risk stratification. Design, Setting, and Participants: A cohort study of 3225 white men was conducted as a secondary analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) chemoprevention trial, a 4-year, randomized, double-blind, placebo-controlled multicenter study conducted from March 2003 to April 2009 to evaluate the safety and efficacy of dutasteride in reducing PCa events. Participants were confirmed to be cancer free by prostate biopsy (6-12 cores) within 6 months prior to the study and underwent 10 core biopsies every 2 years per protocol. The dates for performing data analysis were from July 2016 to October 2019. Interventions: A well-established, population-standardized GRS was calculated for each participant based on 110 known PCa risk-associated single-nucleotide polymorphisms, which is a relative risk compared with the general population. Men were classified into 3 GRS risk groups based on predetermined cutoff values: low (\u3c0.50), average (0.50-1.49), and high (≥1.50). Main Outcomes and Measures: Prostate cancer diagnosis-free survival among men of different risk groups. Results: Among 3225 men (median age, 63 years [interquartile range, 58-67 years]) in the study, 683 (21%) were classified as low risk, 1937 (60%) as average risk, and 605 (19%) as high risk based on GRS alone. In comparison, 2789 (86%) were classified as low or average risk and 436 (14%) as high risk based on FH alone. Men in higher GRS risk groups had a PCa diagnosis-free survival rate that was worse than that of those in the lower GRS risk group (χ2 = 53.3; P \u3c .001 for trend) and in participants with a negative FH of PCa (χ2 = 45.5; P \u3c .001 for trend). Combining GRS and FH further stratified overall genetic risk, indicating that 957 men (30%) were at high genetic risk (either high GRS or positive FH), 1667 men (52%) were at average genetic risk (average GRS and negative FH), and 601 men (19%) were at low genetic risk (low GRS and negative FH). The median PCa diagnosis-free survival was 74 years (95% CI, 73-75 years) for men at high genetic risk, 77 years (95% CI, 75 to \u3e80 years) for men at average genetic risk, and more than 80 years (95% CI, \u3e80 to \u3e80 years) for men at low genetic risk. In contrast, the median PCa diagnosis-free survival was 73 years (95% CI, 71-76 years) for men with a positive FH and 77 years (95% CI, 76-79 years) for men with a negative FH. Conclusions and Relevance: This study suggests that a GRS is significantly associated with patient age at PCa diagnosis. Combining FH and GRS may better stratify inherited risk than FH alone for developing personalized PCa screening strategies

Bioremediation of mercury: not properly exploited in contaminated soils!

© 2017, Springer-Verlag Berlin Heidelberg. Contamination of land and water caused by heavy metal mercury (Hg) poses a serious threat to biota worldwide. The seriousness of toxicity of this neurotoxin is characterized by its ability to augment in food chains and bind to thiol groups in living tissue. Therefore, different remediation approaches have been implemented to rehabilitate Hg-contaminated sites. Bioremediation is considered as cheaper and greener technology than the conventional physico-chemical means. Large-scale use of Hg-volatilizing bacteria are used to clean up Hg-contaminated waters, but there is no such approach to remediate Hg-contaminated soils. This review focuses on recent uses of Hg-resistant bacteria in bioremediation of mercury-contaminated sites, limitation and advantages of this approach, and identifies the gaps in existing research

Targeting the master regulator mTOR: A new approach to prevent the neurological of consequences of parasitic infections?

© 2017 The Author(s). A systematic analysis of 240 causes of death in 2013 revealed that parasitic diseases were responsible for more than one million deaths. The vast majority of these fatalities resulted from protozoan infections presenting with neurological sequelae. In the absence of a vaccine, development of effective therapies is essential to improving global public health. In 2015, an intriguing strategy to prevent cerebral malaria was proposed by Gordon et al. 2015 mBio, 6:e00625. Their study suggested that inhibition of the mammalian target of rapamycin prevented experimental cerebral malaria by blocking the damage to the blood brain barrier and stopping the accumulation of parasitized red blood cells and T cells in the brain. Here, we hypothesize that the same therapeutic strategy could be adopted for other protozoan infections with a brain tropism, to prevent cerebral parasitosis by limiting pathogen replication and preventing immune mediated destruction of brain tissue

Gene cassette transcription in a large integron-associated array

<p>Abstract</p> <p>Background</p> <p>The integron/gene cassette system is a diverse and effective adaptive resource for prokaryotes. Short cassette arrays, with less than 10 cassettes adjacent to an integron, provide this resource through the expression of cassette-associated genes by an integron-borne promoter. However, the advantage provided by large arrays containing hundreds of cassettes is less obvious. In this work, using the 116-cassette array of <it>Vibrio </it>sp. DAT722 as a model, we investigated the theory that the majority of genes contained within large cassette arrays are widely expressed by intra-array promoters in addition to the integron-borne promoter.</p> <p>Results</p> <p>We demonstrated that the majority of the cassette-associated genes in the subject array were expressed. We further showed that cassette expression was conditional and that the conditionality varied across the array. We finally showed that this expression was mediated by a diversity of cassette-borne promoters within the array capable of responding to environmental stressors.</p> <p>Conclusions</p> <p>Widespread expression within large gene cassette arrays could provide an adaptive advantage to the host in proportion to the size of the array. Our findings explained the existence and maintenance of large cassette arrays within many prokaryotes. Further, we suggested that repeated rearrangement of cassettes containing genes and/or promoters within large arrays could result in the assembly of operon-like groups of co-expressed cassettes within an array. These findings add to our understanding of the adaptive repertoire of the integron/gene cassette system in prokaryotes and consequently, the evolutionary impact of this system.</p

Virulence not linked with vegetative compatibility groups in Australian cotton Verticillium dahliae isolates

Verticillium dahliae, the causal agent of Verticillium wilt, is a soil-borne ascomycete that infects numerous agriculturally important crops globally, including cotton. As a billion-dollar industry, cotton is economically important to Australia and the management of disease such as Verticillium wilt is key for the success of the industry. Internationally, defoliating V. dahliae isolates belonging to Vegetative Compatibility Group (VCG) 1A cause severe damage to cotton, while non-defoliating VCG2A isolates result in significantly less disease. However, in Australia, VCG2A is causing more severe damage to crops in the field than the defoliating VCG1A. This study aimed to replicate field observations in controlled greenhouse conditions. We examined and compared disease symptoms on a range of Australian commercial cotton varieties when inoculated with different V. dahliae VCGs. Seedlings were root dipped in conidial suspensions and assessed over seven weeks. The final disease score, disease over time and root length were analysed. Plant mortality resulted from both V. dahliae VCG1A and VCG2A isolates across all cotton varieties used, confirming that there are virulent VCG2A isolates present in Australia. To our knowledge, although virulent on other plant hosts, V. dahliae VCG2A has not previously been reported to be highly virulent in cotton. We infer that virulence cannot be defined solely by VCG in Australian V. dahliae isolates causing disease in cotton

Clinically Relevant Interactions between Newer Antidepressants and Second-Generation Antipsychotics

INTRODUCTION: Combinations of newer antidepressants and second-generation antipsychotics (SGAs) are frequently used by clinicians. Pharmacokinetic drug interaction (PK DI) and poorly understood pharmacodynamic (PD) drug interaction (PD DI) can occur between them. AREAS COVERED: This paper comprehensively reviews PD DI and PK DI studies. EXPERT OPINION: More PK DI studies are needed to better establish dose correction factors after adding fluoxetine and paroxetine to aripiprazole, iloperidone and risperidone. Further PK DI studies and case reports are also needed to better establish the need for dose correction factors after adding i) fluoxetine to clozapine, lurasidone, quetiapine and olanzapine; ii) paroxetine to olanzapine; iii) fluvoxamine to asenapine, aripiprazole, iloperidone, lurasidone, olanzapine, quetiapine and risperidone; iv) high sertraline doses to aripiprazole, clozapine, iloperidone and risperidone: v) bupropion and duloxetine to aripiprazole, clozapine, iloperidone and risperidone; and vi) asenapine to paroxetine and venlafaxine. Possible beneficial PD DI effects occur after adding SGAs to newer antidepressants for treatment-resistant major depressive and obsessive-compulsive disorders. The lack of studies combining newer antidepressants and SGAs in psychotic depression is worrisome. PD DIs between newer antidepressants and SGAs may be more likely for mirtazapine and bupropion. Adding selective serotonin reuptake inhibitors and SGAs may increase QTc interval and may very rarely contribute to torsades de pointes

Environmental DNA signatures distinguish between tsunami and storm deposition in overwash sand

AbstractSandy onshore deposits from tsunamis are difficult to distinguish from storm deposits, which makes it difficult to assess coastal hazards from the geological record. Here we analyse environmental DNA from microbial communities preserved in known tsunami and storm-deposited sediments and intercalating soils and non-marine sediments near Cuddalore, India, and Phra Thong Island, Thailand. Both sites were impacted by the 2004 Indian Ocean Tsunami and a subsequent storm flooding event (2011 Cyclone Thane at Cuddalore and a 2007 storm at Phra Thong Island). We show that the microbial communities in the overwash deposits are significantly different from soil and sediments that are not derived by overwash processes at both locations. Our method also successfully discriminates between modern tsunami deposits and storm deposits. We suggest molecular techniques have the potential to accurately discriminate overwash deposits from catastrophic natural events.</jats:p

Crystal Structure of an Integron Gene Cassette-Associated Protein from Vibrio cholerae Identifies a Cationic Drug-Binding Module

Background The direct isolation of integron gene cassettes from cultivated and environmental microbial sources allows an assessment of the impact of the integron/gene cassette system on the emergence of new phenotypes, such as drug resistance or virulence. A structural approach is being exploited to investigate the modularity and function of novel integron gene cassettes. Methodology/Principal Findings We report the 1.8 A crystal structure of Cass2, an integron-associated protein derived from an environmental V. cholerae. The structure defines a monomeric beta-barrel protein with a fold related to the effector-binding portion of AraC/XylS transcription activators. The closest homologs of Cass2 are multi-drug binding proteins, such as BmrR. Consistent with this, a binding pocket made up of hydrophobic residues and a single glutamate side chain is evident in Cass2, occupied in the crystal form by polyethylene glycol. Fluorescence assays demonstrate that Cass2 is capable of binding cationic drug compounds with submicromolar affinity. The Cass2 module possesses a protein interaction surface proximal to its drug-binding cavity with features homologous to those seen in multi-domain transcriptional regulators. Conclusions/Significance Genetic analysis identifies Cass2 to be representative of a larger family of independent effector-binding proteins associated with lateral gene transfer within Vibrio and closely-related species. We propose that the Cass2 family not only has capacity to form functional transcription regulator complexes, but represents possible evolutionary precursors to multi-domain regulators associated with cationic drug compounds.National Health and Medical Research Council (Australia) (NHMRC grant 488502)National Institutes of Health (U.S.) (Grant GM62414-0 )Ontario. Ministry of Revenue (Challenge Fund

Foreign Policy and the Ideology of Post-ideology: The Case of Matteo Renzi’s Partito Democratico

The post-communist Italian Left has experienced a long phase of ideational misalignment between ideas placed at different levels, as a qualified discursive institutionalist approach demonstrates. Background public philosophies have often clashed with post-communist political ideology, while foreign policy programmes have often contradicted specific policies. Under the leadership of Matteo Renzi, however, the PD is now experiencing a moment of remarkable ideational consistency. Rather than being founded on entirely new premises, this new consensus folds old elements into new ones and shows all the defining traits of post-ideology. Yet, by espousing post-ideology, Renzi is making an ultimately ideological move whose limitations may soon start to show