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The worst Ebola virus (EV) outbreak in history has hit Liberia, Sierra Leone and Guinea hardest and the trend lines in this crisis are grave, and now represents a global public health threat concern. Limited therapeutic and/or prophylactic options are available for people suffering from Ebola virus disease (EVD) and

The worst Ebola virus (EV) outbreak in history has hit Liberia, Sierra Leone and Guinea hardest and the trend lines in this crisis are grave, and now represents a global public health threat concern. Limited therapeutic and/or prophylactic options are available for people suffering from Ebola virus disease (EVD) and further complicate the situation. Previous studies suggested that the EV glycoprotein (GP) is the main determinant causing structural damage of endothelial cells that triggers the hemorrhagic diathesis, but molecular mechanisms underlying this phenomenon remains elusive. Using the informational spectrum method (ISM), a virtual spectroscopy method for analysis of the protein-protein interactions, the interaction of GP with endothelial extracellular matrix (ECM) was investigated. Presented results of this in silico study suggest that Elastin Microfibril Interface Located Proteins (EMILINs) are involved in interaction between GP and ECM. This finding could contribute to a better understanding of EV/endothelium interaction and its role in pathogenesis, prevention and therapy of EVD.

ContributorsVeljkovic, Veljko (Author) / Glisic, Sanja (Author) / Muller, Claude P. (Author) / Scotch, Matthew (Author) / Branch, Donald R. (Author) / Perovic, Vladimir R. (Author) / Sencanski, Milan (Author) / Veljkovic, Nevena (Author) / Colombatti, Alfonso (Author) / College of Health Solutions (Contributor)
Created2015-02-19
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Description

LL-37, a cationic antimicrobial peptide, has numerous immune-modulating effects. However, the identity of a receptor that mediates the responses in immune cells remains uncertain. We have recently demonstrated that LL-37 interacts with the αMI-domain of integrin αMβ2 (Mac-1), a major receptor on the surface of myeloid cells, and induces a

LL-37, a cationic antimicrobial peptide, has numerous immune-modulating effects. However, the identity of a receptor that mediates the responses in immune cells remains uncertain. We have recently demonstrated that LL-37 interacts with the αMI-domain of integrin αMβ2 (Mac-1), a major receptor on the surface of myeloid cells, and induces a migratory response in Mac-1-expressing monocyte/macrophages as well as activation of Mac-1 on neutrophils. Here, we show that LL-37 and its C-terminal derivative supported strong adhesion of various Mac-1-expressing cells, including human embryonic kidney cells stably transfected with Mac-1, human U937 monocytic cells, and murine IC-21 macrophages. The cell adhesion to LL-37 was partially inhibited by specific Mac-1 antagonists, including monoclonal antibody against the αM integrin subunit and neutrophil inhibitory factor, and completely blocked when anti-Mac-1 antibodies were combined with heparin, suggesting that cell surface heparan sulfate proteoglycans act cooperatively with integrin Mac-1. Coating both gram-negative and gram-positive bacteria with LL-37 significantly potentiated their phagocytosis by macrophages, and this process was blocked by a combination of anti-Mac-1 monoclonal antibody and heparin. Furthermore, phagocytosis by wild-type murine peritoneal macrophages of LL-37-coated latex beads, a model of foreign surfaces, was several fold higher than that of untreated beads. In contrast, LL-37 failed to augment phagocytosis of beads by Mac-1-deficient macrophages. These results identify LL-37 as a novel ligand for integrin Mac-1 and demonstrate that the interaction between Mac-1 on macrophages and bacteria-bound LL-37 promotes phagocytosis.

ContributorsLishko, Valeryi (Author) / Moreno, Benjamin (Author) / Podolnikova, Nataly (Author) / Ugarova, Tatiana (Author) / College of Health Solutions (Contributor)
Created2016-07-07
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Description

This manuscript explores the role of embodied views of language comprehension and production in bilingualism and specific language impairment. Reconceptualizing popular models of bilingual language processing, the embodied theory is first extended to this area. Issues such as semantic grounding in a second language and potential differences between early and

This manuscript explores the role of embodied views of language comprehension and production in bilingualism and specific language impairment. Reconceptualizing popular models of bilingual language processing, the embodied theory is first extended to this area. Issues such as semantic grounding in a second language and potential differences between early and late acquisition of a second language are discussed. Predictions are made about how this theory informs novel ways of thinking about teaching a second language. Secondly, the comorbidity of speech, language, and motor impairments and how embodiment theory informs the discussion of the etiology of these impairments is examined. A hypothesis is presented suggesting that what is often referred to as specific language impairment may not be so specific due to widespread subclinical motor deficits in this population. Predictions are made about how weaknesses and instabilities in speech motor control, even at a subclinical level, may disrupt the neural network that connects acoustic input, articulatory motor plans, and semantics. Finally, I make predictions about how this information informs clinical practice for professionals such as speech language pathologists and occupational and physical therapists. These new hypotheses are placed within the larger framework of the body of work pertaining to semantic grounding, action-based language acquisition, and action-perception links that underlie language learning and conceptual grounding.

ContributorsAdams, Ashley (Author) / College of Health Solutions (Contributor)
Created2016-08-17
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Description

We formulate an in silico model of pathogen avoidance mechanism and investigate its impact on defensive behavioural measures (e.g., spontaneous social exclusions and distancing, crowd avoidance and voluntary vaccination adaptation). In particular, we use SIR(B)S (e.g., susceptible-infected-recovered with additional behavioural component) model to investigate the impact of homo-psychologicus aspects of

We formulate an in silico model of pathogen avoidance mechanism and investigate its impact on defensive behavioural measures (e.g., spontaneous social exclusions and distancing, crowd avoidance and voluntary vaccination adaptation). In particular, we use SIR(B)S (e.g., susceptible-infected-recovered with additional behavioural component) model to investigate the impact of homo-psychologicus aspects of epidemics. We focus on reactionary behavioural changes, which apply to both social distancing and voluntary vaccination participations. Our analyses reveal complex relationships between spontaneous and uncoordinated behavioural changes, the emergence of its contagion properties, and mitigation of infectious diseases. We find that the presence of effective behavioural changes can impede the persistence of disease. Furthermore, it was found that under perfect effective behavioural change, there are three regions in the response factor (e.g., imitation and/or reactionary) and behavioural scale factor (e.g., global/local) factors ρ–α behavioural space. Mainly, (1) disease is always endemic even in the presence of behavioural change, (2) behavioural-prevalence plasticity is observed and disease can sometimes be eradication, and (3) elimination of endemic disease under permanence of permanent behavioural change is achieved. These results suggest that preventive behavioural changes (e.g., non-pharmaceutical prophylactic measures, social distancing and exclusion, crowd avoidance) are influenced by individual differences in perception of risks and are a salient feature of epidemics. Additionally, these findings indicates that care needs to be taken when considering the effect of adaptive behavioural change in predicting the course of epidemics, and as well as the interpretation and development of the public health measures that account for spontaneous behavioural changes.

Created2015-10-14
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Description

Tree-like structures are ubiquitous in nature. In particular, neuronal axons and dendrites have tree-like geometries that mediate electrical signaling within and between cells. Electrical activity in neuronal trees is typically modeled using coupled cable equations on multi-compartment representations, where each compartment represents a small segment of the neuronal membrane. The

Tree-like structures are ubiquitous in nature. In particular, neuronal axons and dendrites have tree-like geometries that mediate electrical signaling within and between cells. Electrical activity in neuronal trees is typically modeled using coupled cable equations on multi-compartment representations, where each compartment represents a small segment of the neuronal membrane. The geometry of each compartment is usually defined as a cylinder or, at best, a surface of revolution based on a linear approximation of the radial change in the neurite. The resulting geometry of the model neuron is coarse, with non-smooth or even discontinuous jumps at the boundaries between compartments. We propose a hyperbolic approximation to model the geometry of neurite compartments, a branched, multi-compartment extension, and a simple graphical approach to calculate steady-state solutions of an associated system of coupled cable equations. A simple case of transient solutions is also briefly discussed.

Created2014-07-09
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Description

A key factor in the effectiveness of the seasonal influenza vaccine is its immunological compatibility with the circulating viruses during the season. Here we propose a new bioinformatics approach for analysis of influenza viruses which could be used as an efficient tool for selection of vaccine viruses, assessment of the

A key factor in the effectiveness of the seasonal influenza vaccine is its immunological compatibility with the circulating viruses during the season. Here we propose a new bioinformatics approach for analysis of influenza viruses which could be used as an efficient tool for selection of vaccine viruses, assessment of the effectiveness of seasonal influenza vaccines, and prediction of the epidemic/pandemic potential of novel influenza viruses.

ContributorsVeljkovic, Veljko (Author) / Paessler, Slobodan (Author) / Glisic, Sanja (Author) / Prljic, Jelena (Author) / Perovic, Vladimir R. (Author) / Veljkovic, Nevena (Author) / Scotch, Matthew (Author) / College of Health Solutions (Contributor)
Created2015-12-22
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Description

Manual therapy has long been a component of physical rehabilitation programs, especially to treat those in pain. The mechanisms of manual therapy, however, are not fully understood, and it has been suggested that its pain modulatory effects are of neurophysiological origin and may be mediated by the descending modulatory circuit.

Manual therapy has long been a component of physical rehabilitation programs, especially to treat those in pain. The mechanisms of manual therapy, however, are not fully understood, and it has been suggested that its pain modulatory effects are of neurophysiological origin and may be mediated by the descending modulatory circuit. Therefore, the purpose of this review is to examine the neurophysiological response to different types of manual therapy, in order to better understand the neurophysiological mechanisms behind each therapy’s analgesic effects. It is concluded that different forms of manual therapy elicit analgesic effects via different mechanisms, and nearly all therapies appear to be at least partially mediated by descending modulation. Additionally, future avenues of mechanistic research pertaining to manual therapy are discussed.

ContributorsVigotsky, Andrew (Author) / Bruhns, Ryan P. (Author) / College of Health Solutions (Contributor)
Created2015-11-29
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Study Aim: This study examined the item difficulty and item discrimination scores for the HRFK PE Metrics cognitive assessment tool for 5th-grade students.

Materials and Methods: Ten elementary physical education teachers volunteered to participate. Based on convenience, participating teachers selected two 5th grade physical education classes. Teachers then gave students (N

Study Aim: This study examined the item difficulty and item discrimination scores for the HRFK PE Metrics cognitive assessment tool for 5th-grade students.

Materials and Methods: Ten elementary physical education teachers volunteered to participate. Based on convenience, participating teachers selected two 5th grade physical education classes. Teachers then gave students (N = 633) a 28-question paper and pencil HRFK exam using PE Metrics Standards 3 and 4. Item difficulty and discrimination analysis and Rasch Modeling were used data to determine underperforming items.

Results: Analysis suggests that at least three items are problematic. The Rasch Model confirmed this result and identified similar items with high outfit mean square values and low Point Biserial correlation values.

Conclusions: Teachers are in need of valid and reliable HRFK assessment tools. Without the removal of three items in the PE Metrics HRFK exam for 5th-grade students, complete use of the exam could offer incorrect conclusions.

ContributorsHodges, Michael (Author) / Lee, Chong (Author) / Lorenz, Kent (Author) / Cipriani, Daniel (Author) / College of Health Solutions (Contributor)
Created2015-09-08
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Description

We tested the hypothesis that motor planning and programming of speech articulation and verbal short-term memory (vSTM) depend on partially overlapping networks of neural regions. We evaluated this proposal by testing 76 individuals with acute ischemic stroke for impairment in motor planning of speech articulation (apraxia of speech, AOS) and

We tested the hypothesis that motor planning and programming of speech articulation and verbal short-term memory (vSTM) depend on partially overlapping networks of neural regions. We evaluated this proposal by testing 76 individuals with acute ischemic stroke for impairment in motor planning of speech articulation (apraxia of speech, AOS) and vSTM in the first day of stroke, before the opportunity for recovery or reorganization of structure-function relationships. We also evaluated areas of both infarct and low blood flow that might have contributed to AOS or impaired vSTM in each person. We found that AOS was associated with tissue dysfunction in motor-related areas (posterior primary motor cortex, pars opercularis; premotor cortex, insula) and sensory-related areas (primary somatosensory cortex, secondary somatosensory cortex, parietal operculum/auditory cortex); while impaired vSTM was associated with primarily motor-related areas (pars opercularis and pars triangularis, premotor cortex, and primary motor cortex). These results are consistent with the hypothesis, also supported by functional imaging data, that both speech praxis and vSTM rely on partially overlapping networks of brain regions.

ContributorsHickok, Gregory (Author) / Rogalsky, Corianne (Author) / Chen, Rong (Author) / Herskovits, Edward H. (Author) / Townsley, Sarah (Author) / Hillis, Argye E. (Author) / College of Health Solutions (Contributor)
Created2014-08-25
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Description

Primary biliary cirrhosis (PBC) is a chronic progressive liver disease that often leads to fibrosis, cirrhosis, and end-stage liver disease. The diagnosis is made when there is evidence of cholestasis and reactivity to the antimitochondrial antibody. The etiology of PBC is poorly understood; however, several lines of evidence suggest an

Primary biliary cirrhosis (PBC) is a chronic progressive liver disease that often leads to fibrosis, cirrhosis, and end-stage liver disease. The diagnosis is made when there is evidence of cholestasis and reactivity to the antimitochondrial antibody. The etiology of PBC is poorly understood; however, several lines of evidence suggest an environmental factor that triggers a series of immune-mediated inflammatory reactions in the bile ducts in a genetically susceptible individual. Fatigue and pruritus are the most common symptoms of PBC; however, many patients are diagnosed with PBC only based on laboratory abnormalities. The only pharmacological treatment approved for PBC is ursodeoxycholic acid (UDCA). Several controlled studies have shown that UDCA improves liver biochemistries and prolongs transplant-free survival in PBC patients. Nearly 40% of PBC patients do not respond to UDCA, and those patients are at high risk of serious adverse events, such as the development of liver failure. Therefore, newer alternative therapeutic options for PBC are needed. Obeticholic acid is a first-in-class farnesoid X receptor agonist that has been recently evaluated in PBC patients with inadequate response to UDCA, and demonstrated beneficial results in improving liver biochemistries. Several other agents (fibrates and glucocorticoids) have been previously examined in PBC patients with inadequate response to UDCA, and preliminary results showed biochemical improvement. However, large-scale controlled clinical trials are needed to determine the long-term effects of fibrates and glucocorticoids on the clinical outcomes of PBC. Clinical trials of NGM282 (a fibroblast growth factor-19 analog) and Abatacept (a fusion protein composed of the Fc portion of immunoglobulin G1 fused to CTLA4) are currently underway.

ContributorsAli, Ahmad H. (Author) / Byrne, Thomas J. (Author) / Lindor, Keith (Author) / College of Health Solutions (Contributor)
Created2015-09-10