The effect of fight cost structure on fighting behaviour

A common feature of animal populations is the stealing by animals of resources such as food from other animals. This has previously been the subject of a range of modelling approaches, one of which is the so called "producer-scrounger" model. In this model a producer finds a resource that takes some time to be consumed, and some time later a (generally) conspecific scrounger discovers the producer with its resource and potentially attempts to steal it. In this paper we consider a variant of this scenario where each individual can choose to invest an amount of energy into this contest, and the level of investment of each individual determines the probability of it winning the contest, but also the additional cost it has to bear. We analyse the model for a specific set of cost functions and maximum investment levels and show how the evolutionarily stable behaviour depends upon them. In particular we see that for high levels of maximum investment, the producer keeps the resource without a fight for concave cost functions, but for convex functions the scrounger obtains the resource (albeit at some cost)

Perceptions, views and practices regarding antibiotic prescribing and stewardship among hospital physicians in Jakarta, Indonesia: a questionnaire-based survey

Objectives Antibiotic overuse is one of the main drivers of antimicrobial resistance (AMR), especially in low-income and middle-income countries. This study aimed to understand the perceptions and views towards AMR, antibiotic prescribing practice and antimicrobial stewardship (AMS) among hospital physicians in Jakarta, Indonesia. Design Cross-sectional, self-administered questionnaire-based survey, with descriptive statistics, exploratory factor analysis (EFA) to identify distinct underlying constructs in the dataset, and multivariable linear regression of factor scores to analyse physician subgroups. Setting Six public and private acute-care hospitals in Jakarta in 2019. Participants 1007 of 1896 (53.1% response rate) antibiotic prescribing physicians. Results Physicians acknowledged the significance of AMR and contributing factors, rational antibiotic prescribing, and purpose and usefulness of AMS. However, this conflicted with reported suboptimal local hospital practices, such as room cleaning, hand hygiene and staff education, and views regarding antibiotic decision making. These included insufficiently applying AMS principles and utilising microbiology, lack of confidence in prescribing decisions and defensive prescribing due to pervasive diagnostic uncertainty, fear of patient deterioration or because patients insisted. EFA identified six latent factors (overall Crohnbach’s α=0.85): awareness of AMS activities; awareness of AMS purpose; views regarding rational antibiotic prescribing; confidence in antibiotic prescribing decisions; perception of AMR as a significant problem; and immediate actions to contain AMR. Factor scores differed across hospitals, departments, work experience and medical hierarchy. Conclusions AMS implementation in Indonesian hospitals is challenged by institutional, contextual and diagnostic vulnerabilities, resulting in externalising AMR instead of recognising it as a local problem. Appropriate recognition of the contextual determinants of antibiotic prescribing decision making will be critical to change physicians’ attitudes and develop context-specific AMS interventions

Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration.

Amyotrophic lateral sclerosis (ALS) is a spontaneous, relentlessly progressive motor neuron disease, usually resulting in death from respiratory failure within 3 years. Variation in the genes SOD1 and TARDBP accounts for a small percentage of cases, and other genes have shown association in both candidate gene and genome-wide studies, but the genetic causes remain largely unknown. We have performed two independent parallel studies, both implicating the RNA polymerase II component, ELP3, in axonal biology and neuronal degeneration. In the first, an association study of 1884 microsatellite markers, allelic variants of ELP3 were associated with ALS in three human populations comprising 1483 people (P=1.96 x 10(-9)). In the second, an independent mutagenesis screen in Drosophila for genes important in neuronal communication and survival identified two different loss of function mutations, both in ELP3 (R475K and R456K). Furthermore, knock down of ELP3 protein levels using antisense morpholinos in zebrafish embryos resulted in dose-dependent motor axonal abnormalities [Pearson correlation: -0.49, P=1.83 x 10(-12) (start codon morpholino) and -0.46, P=4.05 x 10(-9) (splice-site morpholino), and in humans, risk-associated ELP3 genotypes correlated with reduced brain ELP3 expression (P=0.01). These findings add to the growing body of evidence implicating the RNA processing pathway in neurodegeneration and suggest a critical role for ELP3 in neuron biology and of ELP3 variants in ALS

ApoSOD1 lacking dismutase activity neuroprotects motor neurons exposed to beta-methylamino-L-alanine through the Ca(2+)/Akt/ERK1/2 prosurvival pathway

Amyotrophic lateral sclerosis (ALS) is a severe human adult-onset neurodegenerative disease affecting lower and upper motor neurons. In >20% of cases, the familial form of ALS is caused by mutations in the gene encoding Cu,Zn-superoxide dismutase (SOD1). Interestingly, administration of wild-type SOD1 to SOD1(G93A) transgenic rats ameliorates motor symptoms through an unknown mechanism. Here we investigated whether the neuroprotective effects of SOD1 are due to the Ca(2+)-dependent activation of such prosurvival signaling pathway and not to its catalytic activity. To this aim, we also examined the mechanism of neuroprotective action of ApoSOD1, the metal-depleted state of SOD1 that lacks dismutase activity, in differentiated motor neuron-like NSC-34 cells and in primary motor neurons exposed to the cycad neurotoxin beta-methylamino-L-alanine (L-BMAA). Preincubation of ApoSOD1 and SOD1, but not of human recombinant SOD1(G93A), prevented cell death in motor neurons exposed to L-BMAA. Moreover, ApoSOD1 elicited ERK1/2 and Akt phosphorylation in motor neurons through an early increase of intracellular Ca(2+) concentration ([Ca(2+)]i). Accordingly, inhibition of ERK1/2 by siMEK1 and PD98059 counteracted ApoSOD1- and SOD1-induced neuroprotection. Similarly, transfection of the dominant-negative form of Akt in NSC-34 motor neurons and treatment with the selective PI3K inhibitor LY294002 prevented ApoSOD1- and SOD1-mediated neuroprotective effects in L-BMAA-treated motor neurons. Furthermore, ApoSOD1 and SOD1 prevented the expression of the two markers of L-BMAA-induced ER stress GRP78 and caspase-12. Collectively, our data indicate that ApoSOD1, which is devoid of any catalytic dismutase activity, exerts a neuroprotective effect through an early activation of Ca(2+)/Akt/ERK1/2 pro-survival pathway that, in turn, prevents ER stress in a neurotoxic model of ALS