Redução do forrageio do iguana-negro-de-cauda-espinhosa, Ctenosaura similis (Sauria: Iguanidae), na presença de estímulos do predador

The presence of a predator may have direct and indirect effects on the behavior of the prey. Although altered behavior may help prey avoid predators, it also can have a potential impact on critical activities such as foraging. Predator-prey interactions are routinely studied in laboratory-based experiments owing to the perceived difficulties of conducting such experiments in natural settings. We conducted an experimental study under field conditions in Palo Verde National Park in northwestern Costa Rica to assess behavioral responses of Black Spiny-tailed Iguanas (Ctenosaura similis) to the presence of predators and predator cues. Free-roaming iguanas were offered mango in designated areas in the presence of a predator (Boa constrictor), a predator cue (B. constrictor feces), and a control (no predator or predator cue). Results indicate that iguanas reduced their foraging efforts in the presence of both a predator and its cue.A presença de um predador pode exercer efeitos diretos e indiretos sobre o comportamento da presa. Embora a alteração do comportamento possa ajudar a presa a evitar predadores, pode também ter um impacto potencial sobre atividades críticas, como o forrageio. As interações predador-presa são comumente estudadas em experimentos de laboratório devido às dificuldades em conduzir experimentos sob condições naturais. Conduzimos um estudo experimental em campo no Parque Nacional Palo Verde, no noroeste da Costa Rica, para avaliar as respostas dos iguanas-negros-de-cauda-espinhosa (Ctenosaura similis) à presença de predadores e de seus estímulos. Oferecemos manga a iguanas livres em áreas pré-estabelecidas na presença de um predador (Boa constrictor), de um estímulo do predador (fezes de B. constrictor) e em uma áreacontrole (sem predador ou estímulo). Os resultados indicam que os iguanas reduziram seus esforços de forrageio tanto na presença do predador como de seu estímulo

Up All Night: The Shifting Roles of Home Media Formats as Transmedia Storytelling

In this age of convergence, where media platforms and industries are becoming increasingly connected and intertwined, ‘transmedia’ has become a buzzword that scholars and industry alike have come to perceive as the media production strategy of the future. When scholars theorise transmedia storytelling, they typically prioritise film, TV, videogames and websites. DVDs and Blu-Rays—physical formats that occupy a vital role in extending and repurposing media content across new terrains—are often overlooked. This chapter will question what specific roles they play in extending stories across media platforms. This chapter explores the specific case studies of Doctor Who and the Marvel Cinematic Universe

Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations1,2. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants3. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS4. Here we assessed the therapeutic potential of RMC-7977 in a comprehensive range of PDAC models. We observed broad and pronounced anti-tumour activity across models following direct RAS inhibition at exposures that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumour versus normal tissues. Treated tumours exhibited waves of apoptosis along with sustained proliferative arrest, whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. In the autochthonous KPC mouse model, RMC-7977 treatment resulted in a profound extension of survival followed by on-treatment relapse. Analysis of relapsed tumours identified Myc copy number gain as a prevalent candidate resistance mechanism, which could be overcome by combinatorial TEAD inhibition in vitro. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS-GTP inhibition in the setting of PDAC and identify a promising candidate combination therapeutic regimen to overcome monotherapy resistance

Towards advancing scientific knowledge of climate change impacts on short-duration rainfall extremes

A large number of recent studies have aimed at understanding short-duration rainfall extremes, due to their impacts on flash floods, landslides and debris flows and potential for these to worsen with global warming. This has been led in a concerted international effort by the INTENSE Crosscutting Project of the GEWEX (Global Energy and Water Exchanges) Hydroclimatology Panel. Here, we summarize the main findings so far and suggest future directions for research, including: the benefits of convection-permitting climate modelling; towards understanding mechanisms of change; the usefulness of temperature-scaling relations; towards detecting and attributing extreme rainfall change; and the need for international coordination and collaboration. Evidence suggests that the intensity of long-duration (1 day+) heavy precipitation increases with climate warming close to the Clausius–Clapeyron (CC) rate (6–7% K−1), although large-scale circulation changes affect this response regionally. However, rare events can scale at higher rates, and localized heavy short-duration (hourly and sub-hourly) intensities can respond more strongly (e.g. 2 × CC instead of CC). Day-to-day scaling of short-duration intensities supports a higher scaling, with mechanisms proposed for this related to local-scale dynamics of convective storms, but its relevance to climate change is not clear. Uncertainty in changes to precipitation extremes remains and is influenced by many factors, including large-scale circulation, convective storm dynamics andstratification. Despite this, recent research has increased confidence in both the detectability and understanding of changes in various aspects of intense short-duration rainfall. To make further progress, the international coordination of datasets, model experiments and evaluations will be required, with consistent and standardized comparison methods and metrics, and recommendations are made for these frameworks

Path dependence and the stabilization of strategic premises: how the funeral industry buries itself

Several studies have shown that path-dependent organizations may pathologically reproduce their paths even in times of crisis. The unchallenged retention of underlying strategic premises seems to play a key role in this selfdestructive process. Whereas the previous literature largely assumes that organizational crises provide sufficient impetus for updating strategic premises, recent empirical studies have highlighted that path-dependent organizations may find this highly difficult. In the present study, I explore how path-dependent organizations stabilize strategic premises even in times of crisis. Drawing on a case study of the funeral industry, I theoretically distill four mechanisms that stabilize strategic premises in path-dependent organizations despite the fierce pressures of organizational crises. While these mechanisms constitute either reflexive modes of processing feedback or generative modes of producing market outcomes, they all inhibit a disconfirmation and, thus, an update of strategic premises. Furthermore, the study presents indicative evidence of how this unchallenged retention of strategic premises leads to the pathological reproduction of the path

Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import

The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

Pharmacological Characterization of Novel Serotonin Transporter Inhibitors Identified Through Computational Structure-Based Virtual Screening

Depression is a mental health disorder affecting greater than 350 million people worldwide with roughly 7% of the United States population diagnosed as of 2017. The selective serotonin reuptake inhibitors (SSRIs) have been the mainstay of pharmacotherapies for depression for the last 40 years. The SSRIs target the serotonin transporter (SERT), a monoamine transporter (MAT) responsible for terminating serotonergic neurotransmission. The SSRIs are not perfect therapeutics and suffer from delayed response times, inconsistent efficacy among patients, and often produce intolerable side effects. Therefore, a strong need exists to develop new antidepressants that are more efficacious and have fewer adverse effects. The Surratt and Madura laboratories approached this problem through the application of computational chemistry and classical pharmacology to rationally identify novel MAT inhibitors and ligands. The work within this doctoral thesis encompasses a structure-based virtual screen targeting SERT and the pharmacological analysis of the compounds identified from the screen. Previous virtual screens utilized SERT homology models based on a bacterial leucine transporter as the structural template (Manepalli et al., 2011; Kortagere et al., 2013; Gabrielsen et al., 2014; Nolan et al., 2014). More recently, the human SERT crystal structure was published by the Eric Gouaux laboratory (Coleman et al., 2016) and used as the template for the present study. The Molecular Operating Environment software was chosen to target the orthosteric binding pocket S1 due to performance during benchmarking evaluations of the scoring function parameters. The HitDiscoverer chemical library was screened with the SERT computational model, and SERT ligand candidates were evaluated by predicted binding affinity, the Lipinski Rule of 5, and chemical uniqueness. Nine compounds were purchased and subjected to pharmacological analysis for binding, inhibition efficacy, and release potential. One compound bound to SERT with reasonable affinity; two compounds inhibited serotonin transport in in vitro assays. None of the compounds promoted the release of internal serotonin (i.e., efflux). In conclusion, computational modeling was successfully used to identify novel inhibitors of the human SERT in a time and cost-efficient manner demonstrating the applicability to academic research

Wireless Advances in the Monitoring of the Human Gastrointestinal Tract

Significant transducer, embedded, and wireless advancements on a novel system, AbStats, has led to the first non-hospital commercialization of a new system called, Wireless AbStats. The architecture for the Wireless AbStats system is presented. This thesis will cover the hardware and software design and implementation of the system, which includes the transducer properties of the acoustic sensor, an embedded node for local storage and wireless communication, a powerful, intermediate smartphone node for data collection, and a server enterprise for further integration with internet services. Additionally, we see improvements made to various aspects of the system, like design, manufacture, and deployment since the previous iteration. Overall, the new capabilities offered by the Wireless AbStats system, which include wireless support, smaller form-factor, and improved signal-to-noise ratio, can lead to new insights and solutions in high-impact and far-reaching problems and applications, such as veterinary care, animal husbandry, neonatal intensive care unit monitoring, and optimal athlete nutrition