scholarly journals Structure of Usutu virus SAAR-1776 displays fusion loop asymmetry

2021 ◽  
Vol 118 (34) ◽  
pp. e2107408118
Author(s):  
Baldeep Khare ◽  
Thomas Klose ◽  
Qianglin Fang ◽  
Michael G. Rossmann ◽  
Richard J. Kuhn
Keyword(s):  
Current Knowledge ◽  
Lipid Binding ◽  
Glycosylation Site ◽  
Usutu Virus ◽  
Host Interactions ◽  
M Proteins ◽  
Current Knowledge Base ◽  
Donated Blood ◽  
Key Residues ◽  
Fusion Loop

Usutu virus (USUV) is an emerging arbovirus in Europe that has been increasingly identified in asymptomatic humans and donated blood samples and is a cause of increased incidents of neuroinvasive human disease. Treatment or prevention options for USUV disease are currently nonexistent, the result of a lack of understanding of the fundamental elements of USUV pathogenesis. Here, we report two structures of the mature USUV virus, determined at a resolution of 2.4 Å, using single-particle cryogenic electron microscopy. Mature USUV is an icosahedral shell of 180 copies of envelope (E) and membrane (M) proteins arranged in the classic herringbone pattern. However, unlike previous reports of flavivirus structures, we observe virus subpopulations and differences in the fusion loop disulfide bond. Presence of a second, unique E glycosylation site could elucidate host interactions, contributing to the broad USUV tissue tropism. The structures provide a basis for exploring USUV interactions with glycosaminoglycans and lectins, the role of the RGD motif as a receptor, and the inability of West Nile virus therapeutic antibody E16 to neutralize the mature USUV strain SAAR-1776. Finally, we identify three lipid binding sites and predict key residues that likely participate in virus stability and flexibility during membrane fusion. Our findings provide a framework for the development of USUV therapeutics and expand the current knowledge base of flavivirus biology.

scholarly journals Factors Influencing the Private Involvement in Urban Rail Public-Private Partnership Projects in China

2017 ◽  
Vol 17 (1) ◽  
pp. 90-106 ◽  
Author(s):  
Yongjian Ke ◽  
Weiya Hao ◽  
Huiping Ding ◽  
Yingying Wang
Keyword(s):  
Influencing Factors ◽  
Current Knowledge ◽  
Group Discussion ◽  
Risk Allocation ◽  
Financial Model ◽  
Urban Rail ◽  
Current Knowledge Base ◽  
Private Investors ◽  
Fiscal Pressure

Private investors have been encouraged to participate in the development and operation of urban rail projects in China through Public-Private Partnerships (PPPs), given the fact that subnational governments are suffering from urgent development demands and severe fiscal pressure. However, there is no formal assessment to determine the private involvement in a PPP project. This problem is particularly critical in the sector of urban rail, in which the huge investment cannot rely on the private sector alone. This study hence aimed to uncover and identify the influencing factors. Multiple research methods, including content analysis, case study and focus group discussion were adopted to achieve the research purpose. Seven types of influencing factors were identified, including project financial model, government fiscal commitment, risk allocation, public accountability, efficiency considerations, policy and regulations, and organisational marketing strategies. The findings add to the current knowledge base by uncovering the drivers behind private involvement in a PPP project. They are also beneficial for industry practitioners as a basis/checklist to determine the private involvement.

Clinical Management of Obsessive-Compulsive and Related Disorders

2017 ◽  
Author(s):  
Samuel R Chamberlain
Keyword(s):  
Body Dysmorphic Disorder ◽  
Current Knowledge ◽  
Assessment Tools ◽  
Future Research ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Medical Issues ◽  
Evidence Based Treatments ◽  
Current Knowledge Base ◽  
Hair Pulling Disorder

Obsessive-compulsive and related disorders (OCRDs) now have their own category in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Disorders currently classified as OCRDs are obsessive-compulsive disorder, trichotillomania (hair pulling disorder), excoriation (skin picking) disorder, hoarding disorder, and body dysmorphic disorder. Collectively, the OCRDs are prevalent, cause considerable functional impairment, and are often overlooked by clinicians. This review surveys current definitions and diagnosis of OCRDs, highlighting recommended assessment tools, differential diagnoses, and medical issues. The heritability of OCRDs is examined, based on available twin data, along with implicated genetic factors. Neurobiological understanding of OCRDs is outlined, focusing on dysregulation of habit generation and top-down response control corticostriatal pathways. The review then highlights evidence-based treatments for OCRDs, which differ considerably between individual disorders. Treatment guidance includes descriptions of target medication doses and therapy content. Lastly, limitations in the current knowledge base for OCRDs are reviewed, with implications for future research directions. This review contains 1 figure, 7 tables, and 40 references. Key words: compulsivity, dopamine, glutamate, impulsivity, screening for OCD, serotonin 

Recruiting and Engaging Men as Fathers in Social Work Practice

2014 ◽  
pp. 235-260
Author(s):  
Joseph Fleming ◽  
Andrew King ◽  
Tara Hunt
Keyword(s):  
Social Work ◽  
Social Workers ◽  
Child Protection ◽  
Current Knowledge ◽  
Social Work Students ◽  
Work Practice ◽  
Social Work Practice ◽  
Research Literature ◽  
Engaging Men ◽  
Current Knowledge Base

Evidence in the research literature suggests that men are usually not engaged by social workers, particularly in child welfare and child protection settings. Mothers also tend to become the focus of intervention, even when there is growing evidence that men can take an active and important role in a child's development in addition to providing support to the mother and family. Whilst there have been some promising developments in including men in social work practice internationally, there remains a gap in the research regarding the engagement of men as fathers in Australia. Given the growing relevance of the topic of fathers, the purpose of this chapter is to add to the current knowledge base, to support social work students and practitioners to engage with men in their role as fathers, and to offer an evidence-based practice model that may assist social workers in their work with men as fathers.

The Important Role of Lipids in Cognitive Impairment

2011 ◽  
pp. 206-211
Author(s):  
Yu Jia ◽  
Zheng Chen ◽  
Jiangyang Lu ◽  
Liu Tingting ◽  
Zhou Liang ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Memory Function ◽  
Pyramidal Cells ◽  
Cholesterol Homeostasis ◽  
Neonatal Lethality ◽  
Somatic Gene ◽  
Current Knowledge Base ◽  
Somatic Gene Transfer ◽  
The Brain

The current knowledge base on circulating serum and plasma risk factors of the cognitive decline of degenerative Alzheimer’s Disease is linked to cholesterol homeostasis and lipoprotein disturbances (i.e., total cholesterol, 24S-hydroxy-cholesterol, lipoprotein(a), or apolipoprotein E. Lipoprotein lipase (LPL) is also expressed in the brain, with the highest levels found in the pyramidal cells of the hippocampus, suggesting a possible role for LPL in the regulation of cognitive function. Little is currently known, however, about the specific role of LPL in the brain. The authors of this chapter have generated an LPL-deficient mouse model that was rescued from neonatal lethality by somatic gene transfer. The levels of the presynaptic marker synaptophysin were reduced in the hippocampus while the levels of the post-synaptic marker PSD-95 remained unchanged in the LPL-deficient mice. The decreased frequency of mEPSC in LPL-deficient neurons indicated that the number of presynaptic vesicles was decreased, which was consistent with the decreases observed in the numbers of total vesicles and docking vesicles. These findings indicate that LPL plays an important role in learning and memory function, possibly by influencing presynaptic function.

scholarly journals Thyroid disorders in subfertility and early pregnancy

2020 ◽  
Vol 11 ◽  
pp. 204201882094585
Author(s):  
Samantha Anandappa ◽  
Mamta Joshi ◽  
Lukasz Polanski ◽  
Paul V. Carroll
Keyword(s):  
Pregnant Women ◽  
Thyroid Function ◽  
Current Knowledge ◽  
Thyroid Autoimmunity ◽  
Thyroid Disorders ◽  
Thyroid Function Tests ◽  
Increased Risk ◽  
Hormone Use ◽  
Current Knowledge Base ◽  
In Pregnancy

Disorders of thyroid function are common in pregnancy and have implications for foetal and maternal health. Thyroid autoimmunity, as evidenced by the presence of elevated levels of anti-thyroid antibodies (anti-TPO and anti-Tg antibodies) is associated with an increased risk of miscarriage, though the mechanism remains poorly understood. There has been considerable focus on the implications and optimal management of pregnant women with thyroid disease, especially those undergoing assisted reproduction. Pregnancy results in significant changes in thyroid physiology and these need to be understood by clinicians involved in the care of pregnant women. Guidelines for the use of thyroxine and target thyroid function tests have been produced by international bodies but it is recognised that these predominantly reflect expert opinion rather than established evidence-based practice. Importantly a number of key clinical trials have been performed to aid understanding, particularly of the consequences of hypothyroidism for mother and baby, and the effectiveness of thyroid hormone use in autoimmune and subclinical hypothyroidism. This review summarises the current knowledge base and guidance for practice relating to thyroid disorders in pregnancy and subfertility.

Predicting Return To Work After Workplace Injury: A Review of Current Literature

2005 ◽  
Vol 11 (2) ◽  
pp. 84-102
Author(s):  
Richard Hilton
Keyword(s):  
Return To Work ◽  
Living Arrangements ◽  
Current Knowledge ◽  
Secondary Analysis ◽  
Demographic Variables ◽  
Predictor Variables ◽  
Workplace Injury ◽  
Research Focus ◽  
Ongoing Research ◽  
Current Knowledge Base

Eighty-four predictor variables were identified from thirty-four studies that researched return to work after workplace injury. The six most studied variables were then critically reviewed. The variables were age, sex, living arrangements, employment maintenance, delay to rehabilitation, and employment type. Based on the number of statistical findings, and on review of the articles, age, employment maintenance, and delay to rehabilitation demonstrated strong relationships with return to work. The variables of sex, living arrangements and employment type did not demonstrate such relationships. While this research brought together the current knowledge base the inability to quantitatively analyse previous results was a major limitation. It was recommended that ongoing research in this area ensures that analysis and publication of results provides information that would allow such secondary analysis in the future. It was also recommended that the current research focus on demographic variables be shifted to more prospective intervention based research.

scholarly journals An Initial Model of Trust in Chatbots for Customer Service—Findings from a Questionnaire Study

2019 ◽  
Vol 31 (3) ◽  
pp. 317-335 ◽  
Author(s):  
Cecilie Bertinussen Nordheim ◽  
Asbjørn Følstad ◽  
Cato Alexander Bjørkli
Keyword(s):  
Customer Service ◽  
Current Knowledge ◽  
Interactive Systems ◽  
Questionnaire Study ◽  
Initial Model ◽  
Related Factors ◽  
Factors Affecting ◽  
Propensity To Trust ◽  
Brand Perception ◽  
Current Knowledge Base

Abstract Chatbots are predicted to play a key role in customer service. Users’ trust in such chatbots is critical for their uptake. However, there is a lack of knowledge concerning users’ trust in chatbots. To bridge this knowledge gap, we present a questionnaire study (N = 154) that investigated factors of relevance for trust in customer service chatbots. The study included two parts: an explanatory investigation of the relative importance of factors known to predict trust from the general literature on interactive systems and an exploratory identification of other factors of particular relevance for trust in chatbots. The participants were recruited as part of their dialogue with one of four chatbots for customer service. Based on the findings, we propose an initial model of trust in chatbots for customer service, including chatbot-related factors (perceived expertise and responsiveness), environment-related factors (risk and brand perceptions) and user-related factors (propensity to trust technology). RESEARCH HIGHLIGHTS We extend the current knowledge base on natural language interfaces by investigating factors affecting users’ trust in chatbots for customer service. Chatbot-related factors, specifically perceived expertise and responsiveness, are found particularly important to users’ trust in such chatbots, but also environment-related factors such as brand perception and user-related factors such as propensity to trust technology. On the basis of the findings, we propose an initial model of users’ trust chatbots for customer service.

Identification of Key Residues in the A-Raf Kinase Important for Phosphoinositide Lipid Binding Specificity

Biochemistry ◽  
2005 ◽  
Vol 44 (9) ◽  
pp. 3432-3440 ◽  
Author(s):  
Lindsey M. Johnson ◽  
Kristy M. James ◽  
M. Dean Chamberlain ◽  
Deborah H. Anderson
Keyword(s):  
Binding Specificity ◽  
Lipid Binding ◽  
Raf Kinase ◽  
Key Residues

scholarly journals Service-Sales Ambidexterity: Evidence, Practice, and Opportunities for Future Research

2019 ◽  
Vol 23 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Ko de Ruyter ◽  
Debbie Isobel Keeling ◽  
Ting Yu
Keyword(s):  
Service Delivery ◽  
Current Practice ◽  
Current Knowledge ◽  
Theoretical Development ◽  
Structural Knowledge ◽  
Future Research ◽  
Organizational Boundaries ◽  
Current Knowledge Base ◽  
Effective Service

Aligning the service-sales interface within and beyond organizational boundaries is worthwhile, yet many firms are not reaping the rewards of such practice. The managerial need for in-depth insights into the blending of selling and service delivery could be better informed through resolution of current open theoretical debates. This position article extends the current knowledge base on the service-sales interface in three ways. First, we offer a synopsis of current scholarly progress on blending service delivery with sales and identify contextual conditions that foster effective service-sales ambidexterity. Second, turning to current practice, we use an empirical case study to demonstrate how a multinational company strategically deploys online learning to bridge structural knowledge and skills gaps within its reseller network to build ambidextrous capacity in the channel and support solution selling. Complementing this human learning approach, we also explore recent advances in machine learning and their impact on the service-sales interface. Third, we blend these academic and practice perspectives to offer a service-sales interface agenda that identifies directions for future research in terms of both the theoretical development of ambidexterity and defining the effective blending of technologies at the service-sales interface that enables ambidexterity in practice.

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