Functional domains of the influenza A virus PB2 protein:identification of NP- and PB1-binding sites

AbstractInfluenza virus genomic RNA segments are packaged into ribonucleoprotein (RNP) structures by the PB1, PB2, and PA subunits of an RNA polymerase and a single-strand RNA-binding nucleoprotein (NP). Assembly and function of these ribonucleoproteins depend on a complex set of protein–protein and protein–RNA interactions. Here, we identify new functional domains of PB2. We show that PB2 contains two regions that bind NP and also identify a novel PB1 binding site. The regions of PB2 responsible for binding NP and PB1 show considerable overlap, and binding of NP to the PB2 fragments could be outcompeted by PB1. The binding domains of PB2 acted as trans-dominant inhibitors of viral gene expression, and consistent with the in vitro binding data, their inhibitory activity depended on the concentration of wild-type PB2, NP, and PB1. This provides evidence for functionally significant and potentially regulatory interactions between PB2 and NP

Managing change – can HR software help?

With the pace of change in the HR and wider business environment seemingly becoming ever-faster, Human Resources teams have a real challenge on their hands to manage any resulting disruption. Employee engagement and morale is at stake, not to mention the reputation of HR, and there is significant pressure to justify the financial implications of any change projects undertaken. In this white paper, HR thought leaders therefore focus on the subject of best-practice change management, whilst providing 'real world' examples from the UK's 11th largest housing association, Together Housing. The white paper also analyses the value of technology to help streamline the potentially disruptive change management process, before sharing tips and advice for those embarking upon their own change journey

Chemotherapy-induced nausea and vomiting: A narrative review to inform dietetics practice

Chemotherapy-induced nausea and vomiting (CINV) are common nutrition-impact symptoms experienced by cancer patients. They exert a detrimental effect on dietary intake, risk of malnutrition and quality of life. While CINV are primarily managed with medication, dietitians play an important role in the management of CINV-related complications such as reduced dietary intake. This review discusses the burden of nausea and vomiting which cancer patients can experience, including its effect on quality of life, nutrition status, and treatment outcomes. Implications for dietetic practice include the need to explore the nature of reported symptoms, identify predisposing risk factors, and to consider the use of a variety of interventions that are individualised to the patient’s symptoms. There are little clinical data regarding effective dietetic interventions for nausea and vomiting. In summary, this review discusses dietetic-related issues surrounding CINV including the pathophysiology, risk factors, prevalence, and both pharmacological and dietetic treatment options

Using Bacterial Nanocellulose as a Plasmonic Biosensor

From the Washington University Office of Undergraduate Research Digest (WUURD), Vol. 12, 05-01-2017. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor: Srikanth Sinamenen

Promoting Sustainable Pro-Poor Growth in Rwandan Agriculture: What are the Policy Options?

In 2000, as part of its strategy for growth and poverty reduction, the Government of Rwanda set a goal to increase per capita income from US$230 to US$900 and halve the incidence of poverty by 2020. Two years after those targets were established Rwanda's first Poverty Reduction Strategy Paper (PRSP) projected that GDP growth in the range of 6 to 7 percent would be needed over the long term for those targets to be realized. The principal sources of growth in the short to medium term were to be the agriculture and manufacturing sectors, with agricultural projected to start at 5.2 percent and accelerate over the period due to productivity improvements. Manufacturing growth was projected to rise sharply to 11.5 percent, based on the expansion of manufacturing capacity in agro-processing, and then slow to a more sustainable level of 7 percent. Between 1995 and 2005, real GDP grew at an average annual rate of 10 percent as the economy recovered from the effects of the 1994 genocide. Real GDP growth is now slowing, however. Between 2001 and 2005, average annual GDP growth averaged only 5.2 percent. If growth continues below 6 percent, this will be insufficient to reach Government's development targets. Government therefore needs to quickly put in place policies to accelerate growth. Transforming the agriculture sector will be a critical element of any growth strategy. Agriculture accounts for 35-40 percent of GDP, and employs around 80 percent of the population. It is also the main source of foreign exchange, and is the primary source of inputs for the manufacturing sector. Yet agricultural growth has been disappointing. Between 2001 and 2005, agricultural growth averaged 4.2 percent per year, below the target range of 5 to 8 percent set out in the PRSP. In recognition of the need to stimulate further sustained growth in agriculture, the government is now poised to identify and prioritize the key interventions. This paper aims to assist government in prioritizing the key measures by examining how the level of agricultural growth needed to achieve the government's policy objectives can be achieved. Some in Rwanda advocate the promotion of export crops, both traditional export crops (e.g., coffee, tea, pyrethrum, hides and skins) and non-traditional export crops (e.g., cut flowers, fruits, vegetables, essential oils, vanilla, silk, macadamia). Others argue that agricultural growth can best be stimulated in the short- to medium-term by increasing productivity in food staples, both crops and livestock. This debate mirrors those ongoing in many other developing countries, in sub-Saharan Africa and elsewhere. An economy-wide, multi-market model (REMM) was developed to test the likely payoffs to alternative agricultural development strategies. The REMM is disaggregated to the sub-national (provincial) level and includes 30 agricultural sectors (commodities) and two aggregate non-agricultural sectors. Eight household types are identified within each province according to size of landholding and gender of household head. The economy-wide model is linked to a micro-simulation model that includes all households sampled in a nationally representative survey (19992001 Household Living Condition Survey). The macro-micro linkage framework permits assessment of the likely impacts of alternative policy scenarios on growth, incomes and poverty, and food security at national, sub-national, and household group levels. The model was first used to simulate a base run scenario representing the "business as usual" option, under which agricultural and non-agricultural growth are assumed to continue along current trends. Alternative growth scenarios were later evaluated relative to this baseline. The modelling results show that business as usual is not an option if Rwanda is to meet its national development targets, including the Millennium Development Goals (MDGs) and the targets agreed to under the New Economic Partnership for Africa's Development (NEPAD). The base run scenario highlights that a continuation of current policies will bring about a modest reduction in the national poverty rate, but the absolute number of people living below the poverty line will increase because of population growth. Food self-sufficiency at the national level will be eroded in the face of demographic pressure and rising food imports. The simulations conducted using the REMM indicate that rapid and sustainable growth in Rwanda's agricultural sector is achievable only if the productivity, profitability, and competitiveness of agriculture is improved. Therefore, the priority measures identified focus on increasing investments in land and water resources, strengthening extension, promoting the performance of both domestic and export markets. Key to this will be strengthening support to producer organizations. The simulations produced a number of insights to inform policy design: - Agriculture has the potential to be a leading engine of growth for Rwanda's economy over the short to medium term - Within agriculture, the main drivers of growth will be food staples, including livestock. - Staple-led growth is more pro-poor than export-led growth. - Growth in staples will reduce the nation's food deficit, but it will not eliminate imports of all commodities. - Growth in agricultural exports will help to reduce the total trade deficit, but it will not be able to eliminate it completely. - Agricultural growth will contribute to the attainment of the first MDG of halving poverty by 2015, but agricultural growth alone will not to be sufficient. These findings from Rwanda are relevant for the many other developing countries, in sub-Saharan Africa and also in other regions, in which policy makers are struggling to unlock the power of agriculture to serve as a driver of growth and poverty reduction. In recent years, much attention has focused on boosting agricultural growth by promoting the development of high-value export crops. The REMM simulation results serve as a reminder that in agrarian economies in which a large proportion of rural households continue to engage in production of food staples destined for home consumption, investments aimed at raising the productivity of food staples are likely to have a much greater impact in the short to medium term in fostering broad-based, pro-poor growth.Environmental Economics and Policy, International Development,

Can the 12-item General Health Questionnaire be used to measure positive mental health?

Background. Well-being is an important determinant of health and social outcomes. Measures of positive mental health states are needed for population-based research. The 12-item General Health Questionnaire (GHQ-12) has been widely used in many settings and languages, and includes positively and negatively worded items. Our aim was to test the hypothesis that the GHQ-12 assesses both positive and negative mental health and that these domains are independent of one another. Method. Exploratory (EFA) and confirmatory (CFA) factor analyses were conducted using data from the British Household Panel Survey (BHPS) and the Health Survey for England (HSE). Regression models were used to assess whether associations with individual and household characteristics varied across positive and negative mental health dimensions. We also explored higher-level variance in these measures, between electoral wards. Results. We found a consistent, replicable factor structure in both datasets. EFA results indicated a two-factor solution, and CFA demonstrated that this was superior to a one-factor model. These factors correspond to ‘symptoms of mental disorder’ and ‘positive mental health’. Further analyses demonstrated independence of these factors in associations with age, gender, employment status, poor housing and household composition. Statistically significant ward-level variance was found for symptoms of mental disorder but not positive mental health. Conclusions. The GHQ-12 measures both positive and negative aspects of mental health, and although correlated, these dimensions have some independence. The GHQ-12 could be used to measure positive mental health in population-based research

Using BNC as Bioplasmonic Sensors

This study aimed to find a technique for using BNC (bacterial nanocellulose) as a plasmonic biosensor with a hot spot localized surface. A template protein (Hb) was imprinted on Au nanorods and was followed with the polymerization of APTMS and TMPS. The protein was then removed to leave an artificial receptor, which enabled protein rebinding. We were successful in developing a procedure for this study, and in the future we will be developing a technique that will allow multiple detection of proteins

Bohl-Perron type stability theorems for linear difference equations with infinite delay

Relation between two properties of linear difference equations with infinite delay is investigated: (i) exponential stability, (ii) \l^p-input \l^q-state stability (sometimes is called Perron's property). The latter means that solutions of the non-homogeneous equation with zero initial data belong to \l^q when non-homogeneous terms are in \l^p. It is assumed that at each moment the prehistory (the sequence of preceding states) belongs to some weighted \l^r-space with an exponentially fading weight (the phase space). Our main result states that (i) $\Leftrightarrow$ (ii) whenever $(p,q) \neq (1,\infty)$ and a certain boundedness condition on coefficients is fulfilled. This condition is sharp and ensures that, to some extent, exponential and \l^p-input \l^q-state stabilities does not depend on the choice of a phase space and parameters $p$ and $q$, respectively. \l^1-input \l^\infty-state stability corresponds to uniform stability. We provide some evidence that similar criteria should not be expected for non-fading memory spaces.Comment: To be published in Journal of Difference Equations and Application

Avoiding Negative Outcomes: Tracking the Mechanisms of Avoidance Learning in Humans During Fear Conditioning

Previous research across species has shown that the amygdala is critical for learning about aversive outcomes, while the striatum is involved in reward-related processing. Less is known, however, about the role of the amygdala and the striatum in learning how to exert control over emotions and avoid negative outcomes. One potential mechanism for active avoidance of stressful situations is postulated to involve amygdala–striatal interactions. The goal of this study was to investigate the physiological and neural correlates underlying avoidance learning in humans. Specifically, we used a classical conditioning paradigm where three different conditioned stimuli (CS) were presented. One stimulus predicted the delivery of a shock upon stimulus offset (CS+), while another predicted no negative consequences (CS−). A third conditioned cue also predicted delivery of a shock, but participants were instructed that upon seeing this stimulus, they could avoid the shock if they chose the correct action (AV+). After successful learning, participants could then easily terminate the shock during subsequent stimulus presentations (AV−). Physiological responses (as measured by skin conductance responses) confirmed a main effect of conditioning, particularly showing higher arousal responses during pre (AV+) compared to post (AV−) learning of an avoidance response. Consistent with animal models, amygdala–striatal interactions were observed to underlie the acquisition of an avoidance response. These results support a mechanism of active coping with conditioned fear that allows for the control over emotional responses such as fears that can become maladaptive and influence our decision-making