Peptide-Gold Nanoparticle Conjugates as Artificial Carbonic Anhydrase Mimics

We herein describe the design and synthesis of a catalytically active peptide–gold nanoparticle conjugate (Pep-Au-NP) that binds Zn(II) within its peptide monolayer and develops carbonic anhydrase activity. Specifically, a modified variant of the β-sheet forming IHIHIQI-peptide (IHQ), which forms an interstrand 3-His Zn(II)-binding site, was used as a ligand for spherical gold nanoparticles (Au-NPs). The resulting immobilized peptide maintains its ability to form β-sheets, as determined by circular dichroism (CD)-spectroscopy and, thus, maintains its ability to form Zn(II)-binding sites. The addition of Zn(II)-ions to the peptide–gold nanoparticle conjugates (Au@IHQ-NP) resulted in significant improvements in rates of ester hydrolysis of 4-nitrophenyl acetate (4-NPA) and the hydration of CO2 compared to the unconjugated peptide variants. Recycling of the catalyst revealed that Au@IHQ-NP remains intact with at least 94% of its initial activity after five rounds of CO2 hydration. The herein reported results reveal that Pep-Au-NPs are able to perform reactions catalyzed by natural metalloenzymes and open up new possibilities for the implementation of these conjugates

Catalytically active peptide–gold nanoparticle conjugates: Prospecting for artificial enzymes

The self‐assembly of peptides onto the surface of gold nanoparticles has emerged as a promising strategy towards the creation of artificial enzymes. The resulting high local peptide density surrounding the nanoparticle leads to cooperative and synergistic effects, which result in rate accelerations and distinct catalytic properties compared to the unconjugated peptide. This Minireview summarizes contributions to and progress made in the field of catalytically active peptide–gold nanoparticle conjugates. The origin of distinct properties, as well as potential applications, are also discussed

Factors affecting outcomes of EU-supported investments in innovation among SMEs in the Greater Poland (Wielkopolska) region, Poland

Purpose The European Union offers support mechanisms to help small and medium sized enterprises (SMEs) to innovate and grow. Given the substantial contribution of SMEs to national economies, the present paper explores what factors tend to be associated with the success of EU-supported innovation by SMEs in Poland during its early post-accession period. Design/methodology/approach A conceptual model relating the type of innovation, investment purpose, funding type and financial readiness, location and collaboration possibilities, company size and sector of operation to changes in the capital base, employment, unit price and revenue is proposed. This model is operationalised and estimated as a structural equations model and estimated using a sample of 110 SMEs surveyed in 2008 in the Greater Poland (Wielkopolska) region in Poland. Findings Two approaches to the successful use of innovation support have been observed among the studied companies. The first approach implements market innovations to establish a presence in foreign markets and to move the product or service up the value chain. The second approach uses the funding to de-risk workforce expansion and increase production capacity. Originality/value The paper provides the first systematic disaggregate level analysis of an early post-accession context where impacts of EU support for SME innovation are decomposed into effects of specific investment conditions and innovation type on changes in capital base, employment, unit price and ultimately revenue. The insights provided here are valuable for managers developing business and innovation strategies on the one hand, but also for policymakers responsible for creating an entrepreneurship friendly environment in emerging economies

What is the ability emotional intelligence test (MSCEIT) good for? An evaluation using item response theory.

The ability approach has been indicated as promising for advancing research in emotional intelligence (EI). However, there is scarcity of tests measuring EI as a form of intelligence. The Mayer Salovey Caruso Emotional Intelligence Test, or MSCEIT, is among the few available and the most widespread measure of EI as an ability. This implies that conclusions about the value of EI as a meaningful construct and about its utility in predicting various outcomes mainly rely on the properties of this test. We tested whether individuals who have the highest probability of choosing the most correct response on any item of the test are also those who have the strongest EI ability. Results showed that this is not the case for most items: The answer indicated by experts as the most correct in several cases was not associated with the highest ability; furthermore, items appeared too easy to challenge individuals high in EI. Overall results suggest that the MSCEIT is best suited to discriminate persons at the low end of the trait. Results are discussed in light of applied and theoretical considerations. © 2014 Fiori et al

Visual dysfunction, but not retinal thinning, following anti-NMDA receptor encephalitis

Objective: To assess structural and functional changes in the afferent visual system following anti-NMDA receptor (NMDAR) encephalitis. Methods: In this cross-sectional study including 31 patients after acute NMDAR encephalitis and matched healthy controls, visual function was assessed as high-contrast visual acuity using Early Treatment Diabetic Retinopathy Study charts and low-contrast sensitivity using Functional Acuity Contrast Test. Retinal changes were measured using optical coherence tomography with assessment of peripapillary retinal nerve fiber layer (pRNFL) and macular intraretinal layer thicknesses. Residual clinical impairment was described using the modified Rankin Scale. Results: High-contrast (logMAR 0.02 ± 0.14 vs −0.09 ± 0.14, p < 0.001) and low-contrast (area under the curve 1.89 ± 0.21 vs 2.00 ± 0.26, p = 0.039) visual acuity were reduced in patients in comparison to healthy controls. More severely affected patients performed worse in visual acuity testing than patients with good recovery (logMAR −0.02 ± 0.11 vs 0.08 ± 0.17, p = 0.030). In contrast, patients did not differ from matched healthy controls in pRNFL or in thickness of intraretinal layers, including the ganglion cell complex, the inner nuclear layer, the outer nuclear and plexiform layers, and the photoreceptor layer. Conclusions: After acute NMDAR encephalitis, patients have mild visual dysfunction in comparison to matched healthy controls, while retinal structure appears unaltered. These observations could point to an impairment of anterior or posterior visual pathway NMDAR function that is similar to dysfunction of NMDAR in cerebral cortex and subcortical structures. Alternatively, residual cognitive impairment might reduce visual function

Temporal visual resolution and disease severity in MS

OBJECTIVE: To examine temporal visual resolution assessed as critical flicker frequency (CFF) in patients with MS and to investigate associations with visual system damage and general disability and cognitive function. METHODS: Thirty-nine patients with MS and 31 healthy controls (HCs) were enrolled in this cross-sectional study and underwent CFF testing, high- and low-contrast visual acuity, alertness and information processing speed using the paced auditory serial addition task (PASAT), and retinal optical coherence tomography (OCT). In patients with MS, visual evoked potentials (VEPs) and Expanded Disability Status Scale (EDSS) scores were assessed. RESULTS: CFF in patients with MS (mean ± SD: 40.9 ± 4.4 Hz) was lower than in HCs (44.8 ± 4.4 Hz, p < 0.001). There was no significant CFF difference between eyes with and without previous optic neuritis (ON). CFF was not associated with visual acuity, VEP latency, the peripapillary retinal nerve fiber layer thickness, and the combined ganglion cell and inner plexiform layer volume. Instead, reduced CFF was associated with worse EDSS scores (r(2) = 0.26, p < 0.001) and alertness (r(2) = 0.42, p = 0.00042) but not with PASAT (p = 0.33). CONCLUSION: CFF reduction in MS occurs independently of ON and structural visual system damage. Its association with the EDSS score and alertness suggests that CFF reflects global disease processes and higher cortical processing rather than focal optic nerve or retinal damage

The Modulation of CD40 Ligand Signaling by Transmembrane CD28 Splice Variant in Human T Cells

The role of CD40 ligand (CD40L)/CD40 signaling in T cell–dependent B cell differentiation and maturation has been amply documented. The mechanism of CD40 signaling in B cells has been well established, whereas the signaling mechanism of CD40L in T cell costimulation remains unknown. In this study we show that CD28i, a transmembrane splice variant of CD28 costimulatory receptor, complexes with CD40L in human T cells. The cross-linking of CD40L resulted in the coendocytosis of CD28i with CD40L. The tyrosine phosphorylation of CD28i followed the cross-linking of CD40L, and the overexpression of CD28i augmented the c-Jun NH2-terminal kinase, p21-activated kinase 2, and nuclear factor κB activation. These data indicate that CD28i, by functioning as a signaling adaptor, transduces CD40L signaling as well as CD28 signaling in human T cells

Development and validation of PozQoL: A scale to assess quality of life of PLHIV

Background: Advances in medical treatment for HIV are driving major changes in HIV policy and practice, including the encouragement of intake and adherence to HIV antiretroviral treatment (ART) by people living with HIV (PLHIV) for both personal and public health benefits. However, there is increasing recognition that achieving these goals will require a concurrent focus on the broader psychological and social wellbeing of PLHIV. Increasingly calls are being been made to incorporate a stronger focus on quality of life (QoL) of PLHIV into HIV prevention policy. In order to achieve this goal, HIV community, support and healthcare services need a valid, short and practical way to evaluate QoL of PLHIV accessing their programs. Current QoL measures are either long, complex, restricted in their use, or expensive. To address these shortcomings, the PozQoL study aimed to develop, test and validate a short and freely available scale assessing QoL among PLHIV. Methods: Drawing on a literature review, the prioritisation of domains and development of the initial pool of items was conducted in consultation with PLHIV community organisations in Australia. The items covered health concerns, psychological, social, and functional wellbeing. Testing involved a baseline and a follow-up survey of 465 adult Australians living with HIV. Participants were recruited through social media and various community organizations nationwide. The survey included the pilot PozQoL scale and other validated measures of health and wellbeing. Results: Guided by an Exploratory Factor Analysis and conceptual considerations, a 13-item scale was developed. The PozQoL scale demonstrated high levels of fit in a Confirmatory Factor Analysis, very good internal consistency, test-retest reliability, and concurrent validity with other measures that approximated different aspects of QoL. Conclusion: The PozQoL scale has been tested in a diverse sample of adult PLHIV living in Australia, demonstrating very good reliability and validity. The insights from PLHIV and other stakeholders supported the balancing of statistical rigour and conceptual accuracy. The scale is now ready to be implemented and field-tested across a range of community, support and healthcare programs for PLHIV. This will make a significant contribution to the evaluation and enhancement of programs for PLHIV

No evidence for retinal damage evolving from reduced retinal blood flow in carotid artery disease

Introduction. Carotid artery disease (CAD) comprising high-grade internal carotid artery stenosis (CAS) or carotid artery occlusion (CAO) may lead to ipsilateral impaired cerebral blood flow and reduced retinal blood supply. Objective. To examine the influence of chronic CAD on retinal blood flow, retinal morphology, and visual function. Methods. Patients with unilateral CAS ≥ 50% (ECST criteria) or CAO were grouped according to the grade of the stenosis and to the flow direction of the ophthalmic artery (OA). Retinal perfusion was measured by transorbital duplex ultrasound, assessing central retinal artery (CRA) blood flow velocities. In addition, optic nerve and optic nerve sheath diameter were measured. Optical coherence tomography (OCT) was performed to study retinal morphology. Visual function was assessed using high- and low-contrast visual paradigms. Results. Twenty-seven patients were enrolled. Eyes with CAS ≥ 80%/CAO and retrograde OA blood flow showed a significant reduction in CRA peak systolic velocity (no-CAD side: 0.130 ± 0.035 m/s, CAS/CAO side: 0.098 ± 0.028; p = 0.005; n = 12). OCT, optic nerve thicknesses, and visual functional parameters did not show a significant difference. Conclusion. Despite assessable hemodynamic effects, chronic high-grade CAD does not lead to gaugeable morphological or functional changes of the retina