Abundance and dynamics of filamentous fungi in the complex ambrosia gardens of the primitively eusocial beetle Xyleborinus saxeseniiRatzeburg (Coleoptera: Curculionidae, Scolytinae)

Insect fungus gardens consist of a community of interacting microorganisms that can have either beneficial or detrimental effects to the farmers. In contrast to fungus-farming ants and termites, the fungal communities of ambrosia beetles and the effects of particular fungal species on the farmers are largely unknown. Here, we used a laboratory rearing technique for studying the filamentous fungal garden community of the ambrosia beetle, Xyleborinus saxesenii, which cultivates fungi in tunnels excavated within dead trees. Raffaelea sulfurea and Fusicolla acetilerea were transmitted in spore-carrying organs by gallery founding females and established first in new gardens. Raffaelea sulfurea had positive effects on egg-laying and larval numbers. Over time, four other fungal species emerged in the gardens. Prevalence of one of them, Paecilomyces variotii, correlated negatively with larval numbers and can be harmful to adults by forming biofilms on their bodies. It also comprised the main portion of garden material removed from galleries by adults. Our data suggest that two mutualistic, several commensalistic and one to two pathogenic filamentous fungi are associated with X. saxesenii. Fungal diversity in gardens of ambrosia beetles appears to be much lower than that in gardens of fungus-culturing ants, which seems to result from essential differences in substrates and behaviour

Computing Aggregate Properties of Preimages for 2D Cellular Automata

Computing properties of the set of precursors of a given configuration is a common problem underlying many important questions about cellular automata. Unfortunately, such computations quickly become intractable in dimension greater than one. This paper presents an algorithm --- incremental aggregation --- that can compute aggregate properties of the set of precursors exponentially faster than na{\"i}ve approaches. The incremental aggregation algorithm is demonstrated on two problems from the two-dimensional binary Game of Life cellular automaton: precursor count distributions and higher-order mean field theory coefficients. In both cases, incremental aggregation allows us to obtain new results that were previously beyond reach

Towards generalized measures grasping CA dynamics

In this paper we conceive Lyapunov exponents, measuring the rate of separation between two initially close configurations, and Jacobians, expressing the sensitivity of a CA's transition function to its inputs, for cellular automata (CA) based upon irregular tessellations of the n-dimensional Euclidean space. Further, we establish a relationship between both that enables us to derive a mean-field approximation of the upper bound of an irregular CA's maximum Lyapunov exponent. The soundness and usability of these measures is illustrated for a family of 2-state irregular totalistic CA

Selective Cholesterol Dynamics between Lipoproteins and Caveolae/Lipid Rafts

Although low-density lipoprotein (LDL) receptor-mediated cholesterol uptake through clathrin-coated pits is now well understood, the molecular details and organizing principles for selective cholesterol uptake/efflux (reverse cholesterol transport, RCT) from peripheral cells remain to be resolved. It is not yet completely clear whether RCT between serum lipoproteins and the plasma membrane occurs primarily through lipid rafts/caveolae or from non-raft domains. To begin to address these issues, lipid raft/caveolae-, caveolae-, and non-raft-enriched fractions were resolved from purified plasma membranes isolated from L-cell fibroblasts and MDCK cells by detergent-free affinity chromatography and compared with detergent-resistant membranes isolated from the same cells. Fluorescent sterol exchange assays between lipoproteins (VLDL, LDL, HDL, apoA1) and these enriched domains provided new insights into supporting the role of lipid rafts/caveolae and caveolae in plasma membrane/lipoprotein cholesterol dynamics:  (i) lipids known to be translocated through caveolae were detected (cholesteryl ester, triacylglycerol) and/or enriched (cholesterol, phospholipid) in lipid raft/caveolae fractions; (ii) lipoprotein-mediated sterol uptake/efflux from lipid rafts/caveolae and caveolae was rapid and lipoprotein specific, whereas that from non-rafts was very slow and independent of lipoprotein class; and (iii) the rate and lipoprotein specificity of sterol efflux from lipid rafts/caveolae or caveolae to lipoprotein acceptors in vitro was slower and differed in specificity from that in intact cellsconsistent with intracellular factors contributing significantly to cholesterol dynamics between the plasma membrane and lipoproteins

Feasibility of aspirin and/or vitamin D3 for men with prostate cancer on active surveillance with Prolaris® testing

OBJECTIVES: To test the feasibility of a randomised controlled trial (RCT) of aspirin and/or vitamin D3 in active surveillance (AS) low/favourable intermediate risk prostate cancer (PCa) patients with Prolaris® testing. PATIENTS AND METHODS: Newly-diagnosed low/favourable intermediate risk PCa patients (PSA ≤ 15 ng/ml, International Society of Urological Pathology (ISUP) Grade Group ≤2, maximum biopsy core length <10 mm, clinical stage ≤cT2c) were recruited into a multi-centre randomised, double-blind, placebo-controlled study (ISRCTN91422391, NCT03103152). Participants were randomised to oral low dose (100 mg), standard dose (300 mg) aspirin or placebo and/or vitamin D3 (4000 IU) versus placebo in a 3 × 2 factorial RCT design with biopsy tissue Prolaris® testing. The primary endpoint was trial acceptance/entry rates. Secondary endpoints included feasibility of Prolaris® testing, 12-month disease re-assessment (imaging/biochemical/histological), and 12-month treatment adherence/safety. Disease progression was defined as any of the following (i) 50% increase in baseline PSA, (ii) new Prostate Imaging-Reporting and Data System (PI-RADS) 4/5 lesion(s) on multi-parametric MRI where no previous lesion, (iii) 33% volume increase in lesion size, or radiological upstaging to ≥T3, (iv) ISUP Grade Group upgrade or (v) 50% increase in maximum cancer core length. RESULTS: Of 130 eligible patients, 104 (80%) accepted recruitment from seven sites over 12 months, of which 94 patients represented the per protocol population receiving treatment. Prolaris® testing was performed on 76/94 (81%) diagnostic biopsies. Twelve-month disease progression rate was 43.3%. Assessable 12-month treatment adherence in non-progressing patients to aspirin and vitamin D across all treatment arms was 91%. Two drug-attributable serious adverse events in 1 patient allocated to aspirin were identified. The study was not designed to determine differences between treatment arms. CONCLUSION: Recruitment of AS PCa patients into a multi-centre multi-arm placebo-controlled RCT of minimally-toxic adjunctive oral drug treatments with molecular biomarker profiling is acceptable and safe. A larger phase III study is needed to determine optimal agents, intervention efficacy, and outcome-associated biomarkers

Photo-antagonism of the GABAA receptor

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation

ANN multiscale model of anti-HIV Drugs activity vs AIDS prevalence in the US at county level based on information indices of molecular graphs and social networks

[Abstract] This work is aimed at describing the workflow for a methodology that combines chemoinformatics and pharmacoepidemiology methods and at reporting the first predictive model developed with this methodology. The new model is able to predict complex networks of AIDS prevalence in the US counties, taking into consideration the social determinants and activity/structure of anti-HIV drugs in preclinical assays. We trained different Artificial Neural Networks (ANNs) using as input information indices of social networks and molecular graphs. We used a Shannon information index based on the Gini coefficient to quantify the effect of income inequality in the social network. We obtained the data on AIDS prevalence and the Gini coefficient from the AIDSVu database of Emory University. We also used the Balaban information indices to quantify changes in the chemical structure of anti-HIV drugs. We obtained the data on anti-HIV drug activity and structure (SMILE codes) from the ChEMBL database. Last, we used Box-Jenkins moving average operators to quantify information about the deviations of drugs with respect to data subsets of reference (targets, organisms, experimental parameters, protocols). The best model found was a Linear Neural Network (LNN) with values of Accuracy, Specificity, and Sensitivity above 0.76 and AUROC > 0.80 in training and external validation series. This model generates a complex network of AIDS prevalence in the US at county level with respect to the preclinical activity of anti-HIV drugs in preclinical assays. To train/validate the model and predict the complex network we needed to analyze 43,249 data points including values of AIDS prevalence in 2,310 counties in the US vs ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4,856 protocols, and 10 possible experimental measures.Ministerio de Educación, Cultura y Deportes; AGL2011-30563-C03-0

Military maladaptation : counterinsurgency and the politics of failure

Tactical learning is critical to battlefield success, especially in a counterinsurgency. This article tests the existing model of military adaption against a ‘most-likely’ case: the British Army’s counterinsurgency in the Southern Cameroons (1960–61). Despite meeting all preconditions thought to enable adaptation – decentralization, leadership turnover, supportive leadership, poor organizational memory, feedback loops, and a clear threat – the British still failed to adapt. Archival evidence suggests politicians subverted bottom-up adaptation, because winning came at too high a price in terms of Britain’s broader strategic imperatives. Our finding identifies an important gap in the extant adaptation literature: it ignores politics.PostprintPeer reviewe

Insect threats and conservation through the lens of global experts

While several recent studies have focused on global insect population trends, all are limited in either space or taxonomic scope. As global monitoring programs for insects are currently not implemented, inherent biases exist within most data. Expert opinion, which is often widely available, proves to be a valuable tool where hard data are limited. Our aim is to use global expert opinion to provide insights on the root causes of potential insect declines worldwide, as well as on effective conservation strategies that could mitigate insect biodiversity loss. We obtained 753 responses from 413 respondents with a wide variety of spatial and taxonomic expertise. The most relevant threats identified through the survey were agriculture and climate change, followed by pollution, while land management and land protection were recognized as the most significant conservation measures. Nevertheless, there were differences across regions and insect groups, reflecting the variability within the most diverse class of eukaryotic organisms on our planet. Lack of answers for certain biogeographic regions or taxa also reflects the need for research in less investigated settings. Our results provide a novel step toward understanding global threats and conservation measures for insects.Peer reviewe