The Influence of Ubiquitin-Related Modifier Protein URM1 on Prion Formation

Prions are infectious proteins that are autocatalyzing (formed by altering a regular protein into the structurally different prion form), and are associated with many neurodegenerative diseases such as Alzheimer\u27s, Parkinson\u27s, Huntington\u27s, and Bovine Spongiform encephalopathy (or Mad Cow disease). This experiment tested the effect of three different plasmids—pH317, pER62, and pMP46—on prion formation in both wild-type and Urm1 deletion mutants in the yeast Saccharomyces cerevisiae. The proposed hypothesis was over-expression of the Ure2 prion forming protein would increase the frequency of prion formation, as well as yield less sustainable prion amyloids (or prion aggregations) that are easier to cure. Another purpose of this experiment was to investigate how the presence or absence of the URM1 gene affects the overall formation of prions. The data showed that over-expression of proteins was seen to increase prion formation, and that over-expression yielding prions were less sustainable across generations. Also shown was that deletion mutants yielded higher numbers of prions than their wild-type counterparts.Curing through use of over-expression and guanidine, which inhibits the chaperone proteins associated with dividing prions during cellular division, proved inconclusive because there was no visible difference between any of the three plasmids

The Influence of Ubiquitin-Related Modifier Protein URM1 on Prion Formation

Prions are infections proteins that are auto-catalyzing (form by altering a regular protein into the structurally different prion form), and are the cause of many common diseases such as Alzheimer\u27s, Parkinson\u27s, Huntington\u27s, and Bovine Spongiform encephalopathy (or Mad Cow disease). This experiment tested the effect of three different plasmids, pH317, pER62 and pmp46 on prion formation in both wild-type and Urm1 deletion mutants in the yeast Saccharomyces cerevisiae. The proposed hypothesis was overexpression of the prion forming protein would increase the frequency of prion formation, as well as yield less sustainable prion amyloids (or prion aggregations) that are easier to cure. Another purpose of this experiment is to investigate how the presence or absence of the URM1 gene, that can form a prion, affects the overall formation of prions. The data showed both that overexpression of proteins was seen to increase prion formation, and that overexpression yielded prions that were less sustainable across generations. Also shown was that deletion mutants yielded higher numbers of prions than their wild-type counterparts. Efforts to cure prions through use of overexpression and guanidine, which inhibits the chaperone proteins associated with dividing prions during cellular division, proved inconclusive because there was no visible difference between any of the three plasmids

The Curious Home

This book describes the work done by the Interaction Research Studio in the Equator Project. Equator was a six-year Interdisciplinary Research Collaboration, funded by the Engineering and Physical Sciences Research Council (EPSRC), that brought together researchers from eight British institutions and a variety of disciplines. The project ended in June 2007 and involved: University of Bristol University of Glasgow Lancaster University University of Nottingham Goldsmiths, University of London University of Southampton University of Sussex University College London The book was published to coincide with the opening of The Curious Home Exhibition at the Pacific Playhouse, London 2007

Evolution of Two Major Zika Virus Lineages: Implications for Pathology, Immune Response, and Vaccine Development

Zika virus (ZIKV) became a public health emergency of global concern in 2015 due to its rapid expansion from French Polynesia to Brazil, spreading quickly throughout the Americas. Its unexpected correlation to neurological impairments and defects, now known as congenital Zika syndrome, brought on an urgency to characterize the pathology and develop safe, effective vaccines. ZIKV genetic analyses have identified two major lineages, Asian and African, which have undergone substantial changes during the past 50 years. Although ZIKV infections have been circulating throughout Africa and Asia for the later part of the 20th century, the symptoms were mild and not associated with serious pathology until now. ZIKV evolution also took the form of novel modes of transmission, including maternal–fetal transmission, sexual transmission, and transmission through the eye. The African and Asian lineages have demonstrated differential pathogenesis and molecular responses in vitro and in vivo. The limited number of human infections prior to the 21st century restricted ZIKV research to in vitro studies, but current animal studies utilize mice deficient in type I interferon (IFN) signaling in order to invoke enhanced viral pathogenesis. This review examines ZIKV strain differences from an evolutionary perspective, discussing how these differentially impact pathogenesis via host immune responses that modulate IFN signaling, and how these differential effects dictate the future of ZIKV vaccine candidates

Threshold devices: looking out from the home

Threshold devices present information gathered from the home’s surroundings to give new views on the domestic situation. We built two prototypes of different threshold devices and studied them in field trials with participant households. The Local Barometer displays online text and images related to the home’s locality depending on the local wind conditions to give an impression of the sociocultural surroundings. The Plane Tracker tracks aircraft passing overhead and imagines their flights onscreen to resource an understanding of the home’s global links. Our studies indicated that the experiences they provided were compelling, that participants could and did interpret the devices in various ways, that their form designs were appropriate for domestic environments, that using ready- made information contributed to the richness of the experiences, and that situating the information they provided with respect to the home and its locality was important for the ways people engaged with them

Local Barometer (Overview)

Threshold devices present information gathered from the home’s surroundings to give new views on the domestic situation. The Local Barometer displays online text and images related to the home’s locality depending on the local wind conditions to give an impression of the sociocultural surroundings

The Plane Tracker (Overview)

The Plane Tracker is an example of a ‘threshold device’ that presents information gathered from the home’s surroundings to give new views on domestic circumstances. A focus on the home and its surroundings complements more traditional applications for domestic computing. Whereas conventional systems for the home focus on bringing placeless and generic content into the home, Threshold devices, in contrast, particularise content by linking it to the home’s physical location. Further examples of Threshold Devices include the ‘Drift Table’, the ‘Local Barometer’ and the ‘Video Window’

Analyst vs. Market Forecasts of Earnings Management to Avoid Small Losses

Burgstahler and Eames (2003) present evidence that analysts commonly anticipate earnings management to avoid small losses, but often incorrectly predict its occurrence. Here we consider whether the market\u27s behavior mimics that of analysts. Our results suggest that analysts exhibit more forecast optimism in their zero earnings forecasts than in their other small earnings forecast levels, and markets exhibit less relative optimism at this point. At the 271-360 day forecast horizon, we find a reduction in the earnings response coefficient at analysts\u27 zero earnings forecasts and interpret this as reflecting less optimism in market earnings forecasts than in analyst forecasts when analysts forecast zero earnings. This evidence is consistent with the market not following analysts in erroneously predicting earnings management to avoid small losses. We do not find similar evidence for shorter forecast horizons, suggesting that market and analyst forecasts converge towards the end of the year. Finding differences in market and analyst earnings forecasts in this loss avoidance environment raises the possibility of differences in a variety of earnings management and other environments, and sends a general note of caution in using analyst forecasts issued early in the year to proxy market expectations. JEL Classification: M41, G14, G24

Chemistry of hydrogen oxide radicals (HO_x) in the Arctic troposphere in spring

We use observations from the April 2008 NASA ARCTAS aircraft campaign to the North American Arctic, interpreted with a global 3-D chemical transport model (GEOS-Chem), to better understand the sources and cycling of hydrogen oxide radicals (HO_x≡H+OH+peroxy radicals) and their reservoirs (HO_y≡HO_x+peroxides) in the springtime Arctic atmosphere. We find that a standard gas-phase chemical mechanism overestimates the observed HO_2 and H_2O_2 concentrations. Computation of HO_x and HO_y gas-phase chemical budgets on the basis of the aircraft observations also indicates a large missing sink for both. We hypothesize that this could reflect HO_2 uptake by aerosols, favored by low temperatures and relatively high aerosol loadings, through a mechanism that does not produce H_2O_2. We implemented such an uptake of HO_2 by aerosol in the model using a standard reactive uptake coefficient parameterization with γ(HO_2) values ranging from 0.02 at 275 K to 0.5 at 220 K. This successfully reproduces the concentrations and vertical distributions of the different HO_x species and HO_y reservoirs. HO_2 uptake by aerosol is then a major HO_x and HO_y sink, decreasing mean OH and HO_2 concentrations in the Arctic troposphere by 32% and 31% respectively. Better rate and product data for HO_2 uptake by aerosol are needed to understand this role of aerosols in limiting the oxidizing power of the Arctic atmosphere

Freqüência de infecção por Toxocara em crianças atendidas em serviço público de Maringá, sul do Brasil

The lack of specific laboratorial diagnosis methods and precise symptoms makes the toxocariasis a neglected disease in Public Health Services. This study aims to determine the frequency of Toxocara spp. infection in children attended by the Health Public Service of Hospital Municipal de Maringá, South Brazil. To evaluate the association of epidemiological and clinical data, an observational and cross-section study was carried out. From 14,690 attended children/year aged from seven month to 12 years old, 450 serum samples were randomly collected from September/2004 to September/2005. A questionnaire was used to evaluate epidemiological, clinical and hematological data. An ELISA using Toxocara canis larval excretory-secretory products as antigen detected 130 (28.8%) positive sera, mainly between children from seven month to five years old (p = 0.0016). Significant correlation was observed between positive serology for Toxocara, and frequent playing in sandbox at school or daycare center (p = 0.011) and the presence of a cat at home (p = 0.056). From the families, 50% were dog owners which exposed soil backyards. Eosinophilia (p = 0.776), and signs and symptoms analyzed (fever p = 0.992, pneumonia p = 0.289, cold-like symptoms p = 0.277, cough p = 0.783, gastrointestinal problems p = 0.877, migraine p = 0.979, abdominal pain p = 0.965, joint pain p = 0.686 and skin rash p = 0.105) could not be related to the presence of anti-Toxocara antibodies. Therefore, two asthmatics children showed titles of 1:10,240 and accentuated eosinophilia (p = 0.0001). The authors emphasize the needs of prevention activities.A falta de métodos de diagnóstico laboratorial específico e sintomas específicos fazem da toxocaríase uma doença negligenciada nos serviços públicos de saúde. Este estudo teve por objetivo determinar a freqüência de infecção por Toxocara spp. em crianças atendidas no serviço público do Hospital Municipal de Maringá, sul do Brasil, e avaliar a associação com dados epidemiológicos e clínicos, em estudo observacional e transversal. De 14.690 crianças/ano atendidas, com idade entre sete meses a 12 anos, foram coletados 450 soros de setembro/2004 a setembro/2005. Um questionário foi utilizado para avaliar dados epidemiológicos, clínicos e hematológicos. Pelo teste ELISA, com antígeno de excreção/secreção de larvas de Toxocara canis, detectou-se 130 (28,8%) soros positivos, principalmente em crianças entre sete meses e cinco anos (p = 0,0016). Houve significante correlação entre sorologia positiva para Toxocara e freqüente recreação das crianças em caixas de areia da escola ou pré escola (p = 0,011) e presença do gato no domicilio (p = 0,056). Das famílias dessas crianças, 50% possuíam cachorros e o quintal com solo exposto. Eosinofilia (p = 0,776), sinais e sintomas (febre p = 0,992, pneumonia p = 0,289, resfriado p = 0,277, tosse p = 0,783, problema gastrointestinal p = 0877, dor de cabeça p = 0,979, dor abdominal p = 0,965, dores articulares p = 0,686, urticária p = 0,105) não se correlacionaram com a soropositividade. Todavia, duas crianças asmáticas apresentaram títulos de 1:10.240 (>; 1:320) e acentuada eosinofilia (p = 0.0001). Os autores enfatizam a necessidade de atividades preventivas