Variation in Decision Making

publication-status: PublishedVariation in how organisms allocate their behavior over their lifetimes is key to determining Darwinian fitness, and thus the evolution of human and non-human decision making. In this chapter, we explore how decision making varies across biologically and societally significant scales and what role such variation plays when trying to understand decision making from an evolutionary perspective. In the process, we highlight the importance of explicitly considering variation both when attempting to predict economically and socially important patterns of behavior, and to obtain a deeper understanding of the fundamental biological processes involved. We conclude by identifying key elements of a framework for incorporating variation into a general theory of Darwinian decision making

Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH

Background Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. Methodology/Principal Findings Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)t​hiazole-4-carboxylateinhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism. Conclusions/Significance These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents

Pharmacists in Pharmacovigilance: Can Increased Diagnostic Opportunity in Community Settings Translate to Better Vigilance?

The pharmacy profession has undergone substantial change over the last two to three decades. Whilst medicine supply still remains a central function, pharmacist’s roles and responsibilities have become more clinic and patient focused. In the community (primary care), pharmacists have become important providers of healthcare as Western healthcare policy advocates patient self-care. This has resulted in pharmacists taking on greater responsibility in managing minor illness and the delivery of public health interventions. These roles require pharmacists to more fully use their clinical skills, and often involve diagnosis and therapeutic management. Community pharmacists are now, more than ever before, in a position to identify, record and report medication safety incidents. However, current research suggests that diagnostic ability of community pharmacists is questionable and they infrequently report to local or national schemes. The aim of this paper is to highlight current practice and suggest ways in which community pharmacy can more fully contribute to patient safety

AIDS-Related Mycoses: Current Progress in the Field and Future Priorities.

Opportunistic fungal infections continue to take an unacceptably heavy toll on the most disadvantaged living with HIV-AIDS, and are a major driver for HIV-related deaths. At the second EMBO Workshop on AIDS-Related Mycoses, clinicians and scientists from around the world reported current progress and key priorities for improving outcomes from HIV-related mycoses

Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.

Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required

Proteomic analysis of Artemisia annua – towards elucidating the biosynthetic pathways of the antimalarial pro-drug artemisinin

Background: MS-based proteomics was applied to the analysis of the medicinal plant Artemisia annua, exploiting a recently published contig sequence database (Graham et al. (2010) Science 327, 328–331) and other genomic and proteomic sequence databases for comparison. A. annua is the predominant natural source of artemisinin, the precursor for artemisinin-based combination therapies (ACTs), which are the WHO-recommended treatment for P. falciparum malaria. Results: The comparison of various databases containing A. annua sequences (NCBInr/viridiplantae, UniProt/ viridiplantae, UniProt/A. annua, an A. annua trichome Trinity contig database, the above contig database and another A. annua EST database) revealed significant differences in respect of their suitability for proteomic analysis, showing that an organism-specific database that has undergone extensive curation, leading to longer contig sequences, can greatly increase the number of true positive protein identifications, while reducing the number of false positives. Compared to previously published data an order-of-magnitude more proteins have been identified from trichome-enriched A. annua samples, including proteins which are known to be involved in the biosynthesis of artemisinin, as well as other highly abundant proteins, which suggest additional enzymatic processes occurring within the trichomes that are important for the biosynthesis of artemisinin. Conclusions: The newly gained information allows for the possibility of an enzymatic pathway, utilizing peroxidases, for the less well understood final stages of artemisinin’s biosynthesis, as an alternative to the known non-enzymatic in vitro conversion of dihydroartemisinic acid to artemisinin. Data are available via ProteomeXchange with identifier PXD000703

Medical mycology and fungal immunology : new research perspectives addressing a major world health challenge

N.A.R.G. is supported by grants from The Wellcome Trust and MRC. M.G.N. is supported by an ERC consolidator grant (no. 310372).Peer reviewedPublisher PD

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

On Classical Equivalence Between Noncritical and Einstein Gravity : The AdS/CFT Perspectives

We find that noncritical gravity, a special class of higher derivative gravity, is classically equivalent to Einstein gravity at the full nonlinear level. We obtain the viscosity-to-entropy ratio and the second order transport coefficients of the dual fluid of noncritical gravity to all orders in the coupling of higher derivative terms. We also compute the holographic entanglement entropy in the dual CFT of noncritical gravity. All these results confirm the nonlinear equivalence between noncritical gravity and Einstein gravity at the classical level.Comment: 19 pages, no figure

Evolution in the Cluster Early-type Galaxy Size-Surface Brightness Relation at z =~ 1

We investigate the evolution in the distribution of surface brightness, as a function of size, for elliptical and S0 galaxies in the two clusters RDCS J1252.9-2927, z=1.237 and RX J0152.7-1357, z=0.837. We use multi-color imaging with the Advanced Camera for Surveys on the Hubble Space Telescope to determine these sizes and surface brightnesses. Using three different estimates of the surface brightnesses, we find that we reliably estimate the surface brightness for the galaxies in our sample with a scatter of < 0.2 mag and with systematic shifts of \lesssim 0.05 mag. We construct samples of galaxies with early-type morphologies in both clusters. For each cluster, we use a magnitude limit in a band which closely corresponds to the rest-frame B, to magnitude limit of M_B = -18.8 at z=0, and select only those galaxies within the color-magnitude sequence of the cluster or by using our spectroscopic redshifts. We measure evolution in the rest-frame B surface brightness, and find -1.41 \+/- 0.14 mag from the Coma cluster of galaxies for RDCS J1252.9-2927 and -0.90 \+/- 0.12 mag of evolution for RX J0152.7-1357, or an average evolution of (-1.13 \+/- 0.15) z mag. Our statistical errors are dominated by the observed scatter in the size-surface brightness relation, sigma = 0.42 \+/- 0.05 mag for RX J0152.7-1357 and sigma = 0.76 \+/- 0.10 mag for RDCS J1252.9-2927. We find no statistically significant evolution in this scatter, though an increase in the scatter could be expected. Overall, the pace of luminosity evolution we measure agrees with that of the Fundamental Plane of early-type galaxies, implying that the majority of massive early-type galaxies observed at z =~ 1 formed at high redshifts.Comment: Accepted in ApJ, 16 pages in emulateapj format with 15 eps figures, 6 in colo