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)

The effect of fight cost structure on fighting behaviour involving simultaneous decisions and variable investment levels

In the “producer–scrounger” model, a producer discovers a resource and is in turn discovered by a second individual, the scrounger, who attempts to steal it. This resource can be food or a territory, and in some situations, potentially divisible. In a previous paper we considered a producer and scrounger competing for an indivisible resource, where each individual could choose the level of energy that they would invest in the contest. The higher the investment, the higher the probability of success, but also the higher the costs incurred in the contest. In that paper decisions were sequential with the scrounger choosing their strategy before the producer. In this paper we consider a version of the game where decisions are made simultaneously. For the same cost functions as before, we analyse this case in detail, and then make comparisons between the two cases. Finally we discuss some real examples with potentially variable and asymmetric energetic investments, including intraspecific contests amongst spiders and amongst parasitoid wasps. In the case of the spiders, detailed estimates of energetic expenditure are available which demonstrate the asymmetric values assumed in our models. For the wasps the value of the resource can affect the probabilities of success of the defender and attacker, and differential energetic investment can be inferred. In general for real populations energy usage varies markedly depending upon crucial parameters extrinsic to the individual such as resource value and intrinsic ones such as age, and is thus an important factor to consider when modelling

β-Amyloid 25-35 Peptide Reduces the Expression of Glutamine Transporter SAT1 in Cultured Cortical Neurons

β-Amyloid (Aβ) peptides may cause malfunction and death of neurons in Alzheimer’s disease. We investigated the effect of Aβ on key transporters of amino acid neurotransmission in cells cultured from rat cerebral cortex. The cultures were treated with Aβ(25-35) at 3 and 10 μM for 12 and 24 h followed by quantitative analysis of immunofluorescence intensity. In mixed neuronal–glial cell cultures (from P1 rats), Aβ reduced the concentration of system A glutamine transporter 1 (SAT1), by up to 50% expressed relative to the neuronal marker microtubule-associated protein 2 (MAP2) in the same cell. No significant effects were detected on vesicular glutamate transporters VGLUT1 or VGLUT2 in neurons, or on glial system N glutamine transporter 1 (SN1). In neuronal cell cultures (from E18 rats), Aβ(25-35) did not reduce SAT1 immunoreactivity, suggesting that the observed effect depends on the presence of astroglia. The results indicate that Aβ may impair neuronal function and transmitter synthesis, and perhaps reduce excitotoxicity, through a reduction in neuronal glutamine uptake

iTRAQ Analysis of Complex Proteome Alterations in 3xTgAD Alzheimer's Mice: Understanding the Interface between Physiology and Disease

Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with accumulation of amyloid β-peptide, synaptic degeneration and the death of neurons in the hippocampus, and temporal, parietal and frontal lobes of the cerebral cortex. Analysis of postmortem brain tissue from AD patients can provide information on molecular alterations present at the end of the disease process, but cannot discriminate between changes that are specifically involved in AD versus those that are simply a consequence of neuronal degeneration. Animal models of AD provide the opportunity to elucidate the molecular changes that occur in brain cells as the disease process is initiated and progresses. To this end, we used the 3xTgAD mouse model of AD to gain insight into the complex alterations in proteins that occur in the hippocampus and cortex in AD. The 3xTgAD mice express mutant presenilin-1, amyloid precursor protein and tau, and exhibit AD-like amyloid and tau pathology in the hippocampus and cortex, and associated cognitive impairment. Using the iTRAQ stable-isotope-based quantitative proteomic technique, we performed an in-depth proteomic analysis of hippocampal and cortical tissue from 16 month old 3xTgAD and non-transgenic control mice. We found that the most important groups of significantly altered proteins included those involved in synaptic plasticity, neurite outgrowth and microtubule dynamics. Our findings have elucidated some of the complex proteome changes that occur in a mouse model of AD, which could potentially illuminate novel therapeutic avenues for the treatment of AD and other neurodegenerative disorders

Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease The DIAN-TU-001 Randomized Clinical Trial

IMPORTANCE Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD). OBJECTIVE To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment. DESIGN, SETTING, AND PARTICIPANTS From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD. Carriers of gene variants were assigned 3:1 to either drug or placebo. The present analysis was conducted from April to June 2023. DIAN-TU-001 spans 25 study sites in 7 countries. Biofluids and neuroimaging from carriers of DIAD gene variants in the gantenerumab, solanezumab, and placebo groups were analyzed. INTERVENTIONS In 2016, initial dosing of gantenerumab, 225 mg (subcutaneously every 4 weeks) was increased every 8 weeks up to 1200 mg. In 2017, initial dosing of solanezumab, 400 mg (intravenously every 4 weeks) was increased up to 1600 mg every 4 weeks. MAIN OUTCOMES AND MEASURES Longitudinal changes in CSF levels of neurogranin, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3–like 1 protein (YKL-40), glial fibrillary acidic protein (GFAP), neurofilament light protein (NfL), and plasma levels of GFAP and NfL. RESULTS Of 236 eligible participants screened, 43 were excluded. A total of 142 participants (mean [SD] age, 44 [10] years; 72 female [51%]) were included in the study (gantenerumab, 52 [37%]; solanezumab, 50 [35%]; placebo, 40 [28%]). Relative to placebo, gantenerumab significantly reduced CSF neurogranin level at year 4 (mean [SD] β = −242.43 [48.04] pg/mL; P < .001); reduced plasma GFAP level at year 1 (mean [SD] β = −0.02 [0.01] ng/mL; P = .02), year 2 (mean [SD] β = −0.03 [0.01] ng/mL; P = .002), and year 4 (mean [SD] β = −0.06 [0.02] ng/mL; P < .001); and increased CSF sTREM2 level at year 2 (mean [SD] β = 1.12 [0.43] ng/mL; P = .01) and year 4 (mean [SD] β = 1.06 [0.52] ng/mL; P = .04). Solanezumab significantly increased CSF NfL (log) at year 4 (mean [SD] β = 0.14 [0.06]; P = .02). Correlation analysis for rates of change found stronger correlations between CSF markers and fluid markers with Pittsburgh compound B positron emission tomography for solanezumab and placebo. CONCLUSIONS AND RELEVANCE This randomized clinical trial supports the importance of fibrillar amyloid reduction in multiple AD-related processes of neuroinflammation and neurodegeneration in CSF and plasma in DIAD. Additional studies of antiaggregated amyloid therapies in sporadic AD and DIAD are needed to determine the utility of nonamyloid biomarkers in determining disease modification

Analysis of Epitopes on Dengue Virus Envelope Protein Recognized by Monoclonal Antibodies and Polyclonal Human Sera by a High Throughput Assay

Dengue virus is the leading cause of arboviral diseases worldwide. The envelope protein is the major target of neutralizing antibodies and vaccine development. While previous studies have reported several epitopes on envelope protein, the possibility of interdomain epitopes and the relationship of epitopes to neutralizing potency remain unexplored. We developed a high throughput dot blot assay by using 67 alanine mutants of surface-exposed envelope residues as a systematic approach to identify epitopes recognized by mouse monoclonal antibodies and polyclonal human sera. Our results suggested the presence of interdomain epitopes more frequent than previously appreciated. Compared with monoclonal antibodies generated by traditional protocol, the potent neutralizing monoclonal antibodies generated by a new protocol showed several unique features of their epitopes. Moreover, the predominant epitopes of antibodies against envelope protein in polyclonal sera can be identified by this assay. These findings have implications for future development of epitope-specific diagnostics and epitope-based dengue vaccine, and add to our understanding of humoral immune responses to dengue virus at the epitope level

Factors Relating to Managerial Stereotypes: The Role of Gender of the Employee and the Manager and Management Gender Ratio

Several studies have shown that the traditional stereotype of a "good" manager being masculine and male still exists. The recent changes in the proportion of women and female managers in organizations could affect these two managerial stereotypes, leading to a stronger preference for feminine characteristics and female leaders. This study examines if the gender of an employee, the gender of the manager, and the management gender ratio in an organization are related to employees' managerial stereotypes. 3229 respondents working in various organizations completed an electronic questionnaire. The results confirm our hypotheses that, although the general stereotype of a manager is masculine and although most prefer a man as a manager, female employees, employees with a female manager, and employees working in an organization with a high percentage of female managers, have a stronger preference for feminine characteristics of managers and for female managers. Moreover, we find that proximal variables are much stronger predictors of these preferences than more distal variables. Our study suggests that managerial stereotypes could change as a result of personal experiences and changes in the organizational context. The results imply that increasing the proportion of female managers is an effective way to overcome managerial stereotyping. This study examines the influence on managerial stereotypes of various proximal and distal factors derived from theory among a large group of employees (in contrast to students)

SPT clusters with des and HST weak lensing. I. Cluster lensing and Bayesian population modeling of multiwavelength cluster datasets

We present a Bayesian population modeling method to analyze the abundance of galaxy clusters identified by the South Pole Telescope (SPT) with a simultaneous mass calibration using weak gravitational lensing data from the Dark Energy Survey (DES) and the Hubble Space Telescope (HST). We discuss and validate the modeling choices with a particular focus on a robust, weak-lensing-based mass calibration using DES data. For the DES Year 3 data, we report a systematic uncertainty in weak-lensing mass calibration that increases from 1% at z=0.25 to 10% at z=0.95, to which we add 2% in quadrature to account for uncertainties in the impact of baryonic effects. We implement an analysis pipeline that joins the cluster abundance likelihood with a multiobservable likelihood for the Sunyaev-Zel'dovich effect, optical richness, and weak-lensing measurements for each individual cluster. We validate that our analysis pipeline can recover unbiased cosmological constraints by analyzing mocks that closely resemble the cluster sample extracted from the SPT-SZ, SPTpol ECS, and SPTpol 500d surveys and the DES Year 3 and HST-39 weak-lensing datasets. This work represents a crucial prerequisite for the subsequent cosmological analysis of the real dataset

SPT clusters with DES and HST weak lensing. I. Cluster lensing and Bayesian population modeling of multiwavelength cluster datasets

We present a Bayesian population modeling method to analyze the abundance of galaxy clusters identified by the South Pole Telescope (SPT) with a simultaneous mass calibration using weak gravitational lensing data from the Dark Energy Survey (DES) and the Hubble Space Telescope (HST). We discuss and validate the modeling choices with a particular focus on a robust, weak-lensing-based mass calibration using DES data. For the DES Year 3 data, we report a systematic uncertainty in weak-lensing mass calibration that increases from 1% at z=0.25 to 10% at z=0.95, to which we add 2% in quadrature to account for uncertainties in the impact of baryonic effects. We implement an analysis pipeline that joins the cluster abundance likelihood with a multiobservable likelihood for the Sunyaev-Zel'dovich effect, optical richness, and weak-lensing measurements for each individual cluster. We validate that our analysis pipeline can recover unbiased cosmological constraints by analyzing mocks that closely resemble the cluster sample extracted from the SPT-SZ, SPTpol ECS, and SPTpol 500d surveys and the DES Year 3 and HST-39 weak-lensing datasets. This work represents a crucial prerequisite for the subsequent cosmological analysis of the real dataset