Plasmodium knowlesi: a superb in vivo nonhuman primate model of antigenic variation in malaria.

Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo. Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated. Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts. Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models. Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi - macaque model systems and summarizing exciting new progress in this area of research

A high-content, multiplexed screen in human breast cancer cells identifies profilin-1 inducers with anti-migratory activities

Profilin-1 (Pfn-1) is a ubiquitously expressed actin-binding protein that is essential for normal cell proliferation and migration. In breast cancer and several other adenocarcinomas, Pfn-1 expression is downregulated when compared to normal tissues. Previous studies from our laboratory have shown that genetically modulating Pfn-1 expression significantly impacts proliferation, migration, and invasion of breast cancer cells in vitro, and mammary tumor growth, dissemination, and metastatic colonization in vivo. Therefore, small molecules that can modulate Pfn-1 expression could have therapeutic potential in the treatment of metastatic breast cancer. The overall goal of this study was to perform a multiplexed phenotypic screen to identify compounds that inhibit cell motility through upregulation of Pfn-1. Screening of a test cassette of 1280 compounds with known biological activities on an Oris™ Pro 384 cell migration platform identified several agents that increased Pfn-1 expression greater than two-fold over vehicle controls and exerted anti-migratory effects in the absence of overt cytotoxicity in MDA-MB-231 human breast cancer cells. Concentration-response confirmation and orthogonal follow-up assays identified two bona fide inducers of Pfn-1, purvalanol and tyrphostin A9, that confirmed in single-cell motility assays and Western blot analyses. SiRNA-mediated knockdown of Pfn-1 abrogated the inhibitory effect of tyrphostin A9 on cell migration, suggesting Pfn-1 is mechanistically linked to tyrphostin A9's anti-migratory activity. The data illustrate the utility of the high-content cell motility assay to discover novel targeted anti-migratory agents by integrating functional phenotypic analyses with target-specific readouts in a single assay platform. © 2014 Joy et al

Investigating in-service failures of water pipes from a multiaxial notch fatigue point of view: A conceptual study

Many mechanisms and processes can cause deterioration and ultimately failure of water distribution pipes during in-service operation, amongst these is damage caused by metal fatigue. This paper summarises an attempt at formalising a novel methodology suitable for estimating the number of years taken for a through thickness fatigue crack to form in this complex scenario. The devised method is based on the so-called modified Wo¨hler curve method and can be applied to estimate fatigue damage of water pipes independently from the degree of multiaxiality and non-proportionality of the load history. The computational approach of the proposed fatigue life estimation technique makes full use of an incremental procedure: fatigue damage is evaluated year by year by assuming that all variable involved in the process can change over time. The detrimental effect of corrosion pits is directly accounted for by treating them as conventional notches whose size increases with time. Finally, by taking as reference information the number of years for a blowout hole to form, the proposed approach is used to show how the lifetime of grey cast iron pipes can be remarkably shortened by fatigue

Opposition as victimhood in newspaper debates about same-sex marriage

In this paper, we take a queer linguistics approach to the analysis of data from British newspaper articles which discuss the introduction of same-sex marriage. Drawing on methods from CDA and corpus linguistics, we focus on the construction of agency in relation to the government extending marriage to same-sex couples, and those resisting this. We show that opponents to same-sex marriage are represented and represent themselves as victims whose moral values, traditions, and civil liberties are being threatened by the state. Specifically, we argue that victimhood is invoked in a way that both enables and permits discourses of implicit homophobia

The Set of Measures on the Reduction of Agrarian Risks in the Conditions of Interstate Integration

Выполнен сравнительный анализ уровня самообеспеченности основными продуктами питания государств-участников ЕАЭС. Выявлены рискообразующие факторы в аграрной сфере и потенциальные угрозы продовольственной безопасности. Обоснована значимость производственных и финансовых аграрных рисков для целей производства необходимого количества сельскохозяйственного сырья и продовольствия в Республике Беларусь. Предложен комплекс мероприятий по снижению уровня аграрных рисков, реализация которых будет способствовать обеспечению необходимых параметров продовольственной безопасности.A comparative analysis of the level of self-provision with essential foods of the countries of Eurasian Economic Union is carried. Risk factors in the agrarian sphere and potential threats for the food security are revealed. The significance of production and financial agrarian risks for the purposes of producing necessary quantity of agricultural raw materials and food in the Republic of Belarus is justified. The set of measures for reducing the level of agrarian risks is proposed, the implementation of which will facilitate providing necessary parameters of food security

Examining the Moderating Role of Rational-Versus Emotional-Focused Websites: The Case of Boutique Hotels

This article examines whether emotional or rational advertising appeals are more effective for website hospitality services. Specifically, it considers how attitudes towards websites, service expectations and attitudes towards boutique hotels may influence the two different types of advertising appeals and purchase intention. Results show that websites using emotional appeals tend to show a positive relationship between attitude towards hotels and attitude towards websites and purchase intention. It also indicates that emotional advertisements are better at gaining and retaining interest and attention, and as such can be highly beneficial for small boutique hotels. This article provides several marketing and business policy implications to aid practitioners and strategists in making better decisions

Species' geographic distributions through time: Playing catchup with changing climates

This is the author's accepted manuscript.Species’ ranges are often treated as a rather fixed characteristic, rather than a fluid, ever-changing manifestation of their ecological requirements and dispersal abilities. Paleontologists generally have had a more flexible point of view on this issue than neontologists, but each perspective can improve by appreciating the other. Here, we provide an overview of paleontological and neontological perspectives on species’ geographic distributions, focusing on what can be learned about historical variations in distributions. The cross-disciplinary view, we hope, offers some novel perspectives on species-level biogeography

Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

<div><p>Background</p><p>In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats.</p><p>Methods</p><p>Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared.</p><p>Results</p><p>By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1–10.1mm) than diabetic (5.9mm, 4.2–9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1–6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0–29.5mm) than in diabetic (15.4mm, 11.2–20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6–17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray.</p><p>Conclusions</p><p>These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.</p></div

Non-opaque soft tissue foreign body: sonographic findings

<p>Abstract</p> <p>Background</p> <p>Soft tissue foreign bodies are a common cause of orthopedic consultation in emergency departments. It is difficult to confirm their existence because conventional radiology only detects radio-opaque foreign bodies. Sonography can be a useful diagnostic method. The aim of this study is to evaluate diagnostic accuracy of sonography in detection and localization of non-opaque foreign bodies.</p> <p>Methods</p> <p>We evaluated 47 patients with suspected foreign body retention in soft tissues by 10 MHz linear array transducer. A single radiologist performed all examinations with 6 years' experience in musculoskeletal Sonography. We detected and localized the presence of the foreign body in the soft tissue as guidance for facilitating the surgery.</p> <p>Results</p> <p>We detected soft tissue foreign body in 45 cases as hyperechoic foci. Posterior acoustic shadowing was seen in 36 cases and halo sign was seen in 5 cases due to abscess or granulation tissue formation. Surgery was performed in 39 patients and 44 foreign bodies were removed.</p> <p>Conclusion</p> <p>Sonography is a useful modality in detection and localization of radiolucent foreign bodies in soft tissue which can avoid misdiagnosis during primary emergency evaluation.</p

Internet-based medical education: a realist review of what works, for whom and in what circumstances

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