Localization of α-synuclein in teleost central nervous system: immunohistochemical and Western blot evidence by 3D5 monoclonal antibody in the common carp, Cyprinus carpio

Alpha synuclein (α-syn) is a 140 amino acid vertebrate-specific protein, highly expressed in the human nervous system and abnormally accumulated in Parkinson's disease and other neurodegenerative disorders, known as synucleinopathies. The common occurrence of α-syn aggregates suggested a role for α-syn in these disorders, although its biological activity remains poorly understood. Given the high degree of sequence similarity between vertebrate α-syns, we investigated this proteins in the CNS of the common carp Cyprinus carpio, with the aim of comparing its anatomical and cellular distribution with that of mammalian α-syn. The distribution of α-syn was analyzed by semiquantitative Western blot, immunohistochemistry and immunofluorescence by a novel monoclonal antibody (3D5) against a fully conserved epitope between carp and human α-syn. The distribution of 3D5 immunoreactivity was also compared with that of ChAT, TH and 5HT by double immunolabelings. Results show that α-syn-like protein of about 17 kDa is expressed to different levels in several brain regions and in the spinal cord. Immunoreactive materials were localized in neuronal perikarya and varicose fibers but not in the nucleus. Present findings indicate that α-syn-like proteins may be expressed in few subpopulations of catecholaminergic and serotoninergic neurons in the carp brain. However, evidence of cellular colocalization 3D5/TH or 3D5/5HT was rare. Differently, the same proteins appear to be co-expressed with ChAT by cholinergic neurons in several motor and reticular nuclei. These results sustain the functional conservation of the α-syn expression in cholinergic systems and suggest that α-syn modulates similar molecular pathways in phylogenetically distant vertebrates. This article is protected by copyright. All rights reserved

Neuropsychological changes in isolated REM sleep behavior disorder: A systematic review and meta-analysis of cross-sectional and longitudinal studies

The aim of this meta-analysis is twofold: (a) to assess cognitive impairments in isolated rapid eye movement (REM) sleep behavior disorder (iRBD) patients compared to healthy controls (HC); (b) to quantitatively estimate the risk of developing a neurodegenerative disease in iRBD patients according to baseline cognitive assessment. To address the first aim, cross-sectional studies including polysomnography-confirmed iRBD patients, HC, and reporting neuropsychological testing were included. To address the second aim, longitudinal studies including polysomnography-confirmed iRBD patients, reporting baseline neuropsychological testing for converted and still isolated patients separately were included. The literature search was conducted based on PRISMA guidelines and the protocol was registered at PROSPERO (CRD42021253427). Cross-sectional and longitudinal studies were searched from PubMed, Web of Science, Scopus, and Embase databases. Publication bias and statistical heterogeneity were assessed respectively by funnel plot asymmetry and using I2. Finally, a random-effect model was performed to pool the included studies. 75 cross-sectional (2,398 HC and 2,460 iRBD patients) and 11 longitudinal (495 iRBD patients) studies were selected. Cross-sectional studies showed that iRBD patients performed significantly worse in cognitive screening scores (random-effects (RE) model = –0.69), memory (RE model = –0.64), and executive function (RE model = –0.50) domains compared to HC. The survival analyses conducted for longitudinal studies revealed that lower executive function and language performance, as well as the presence of mild cognitive impairment (MCI), at baseline were associated with an increased risk of conversion at follow-up. Our study underlines the importance of a comprehensive neuropsychological assessment in the context of iRBD

Fluorescent Nanozeolite Receptors for the Highly Selective and Sensitive Detection of Neurotransmitters in Water and Biofluids

The design and preparation of synthetic binders (SBs) applicable for small biomolecule sensing in aqueous media remains very challenging. SBs designed by the lock-and-key principle can be selective for their target analyte but usually show an insufficient binding strength in water. In contrast, SBs based on symmetric macrocycles with a hydrophobic cavity can display high binding affinities but generally suffer from indiscriminate binding of many analytes. Herein, a completely new and modular receptor design strategy based on microporous hybrid materials is presented yielding zeolite-based artificial receptors (ZARs) which reversibly bind the neurotransmitters serotonin and dopamine with unprecedented affinity and selectivity even in saline biofluids. ZARs are thought to uniquely exploit both the non-classical hydrophobic effect and direct non-covalent recognition motifs, which is supported by in-depth photophysical, and calorimetric experiments combined with full atomistic modeling. ZARs are thermally and chemically robust and can be readily prepared at gram scales. Their applicability for the label-free monitoring of important enzymatic reactions, for (two-photon) fluorescence imaging, and for high-throughput diagnostics in biofluids is demonstrated. This study showcases that artificial receptor based on microporous hybrid materials can overcome standing limitations of synthetic chemosensors, paving the way towards personalized diagnostics and metabolomics

Thermoreversible hyaluronan-hydrogel and autologous nucleus pulposus cell delivery regenerates human intervertebral discs in an ex vivo, physiological organ culture model

Numerous studies show promise for cell-based tissue engineering strategies aiming to repair painful intervertebral disc (IVD) degeneration. However, clinical translation to human IVD repair is slow. In the present study, the regenerative potential of an autologous nucleus pulposus (NP)-cell-seeded thermoresponsive hyaluronic acid hydrogel in human lumbar IVDs was assessed under physiological conditions. First, agarose-encased in vitro constructs were developed, showing greater than 90 % NP cell viability and high proteoglycan deposition within HA-pNIPAM hydrogels following 3 weeks of dynamic loading. Second, a bovine-induced IVD degeneration model was used to optimise and validate T1ρ magnetic resonance imaging (MRI) for detection of changes in proteoglycan content in isolated intact IVDs. Finally, isolated intact human lumbar IVDs were pre-scanned using the established MRI sequence. Then, IVDs were injected with HA-pNIPAM hydrogel alone or autologous NP-cell-seeded. Next, the treated IVDs were cultured under cyclic dynamic loading for 5 weeks. Post-treatment T1ρ values were significantly higher as compared to pre-treatment scans within the same IVD and region of interest. Histological evaluation of treated human IVDs showed that the implanted hydrogel alone accumulated proteoglycans, while those that contained NP cells also displayed neo-matrix-surrounded cells within the gel. The study indicated a clinical potential for repairing early degenerative human IVDs using autologous cells/hydrogel suspensions. This unique IVD culture set-up, combined with the long-term physiological culture of intact human IVDs, allowed for a more clinically relevant evaluation of human tissue repair and regeneration, which otherwise could not be replicated using the available in vitro and in vivo models

Thrombolysis ImPlementation in Stroke (TIPS): evaluating the effectiveness of a strategy to increase the adoption of best evidence practice – protocol for a cluster randomised controlled trial in acute stroke care

BACKGROUND: Stroke is a leading cause of death and disability internationally. One of the three effective interventions in the acute phase of stroke care is thrombolytic therapy with tissue plasminogen activator (tPA), if given within 4.5 hours of onset to appropriate cases of ischaemic stroke. OBJECTIVES: To test the effectiveness of a multi-component multidisciplinary collaborative approach compared to usual care as a strategy for increasing thrombolysis rates for all stroke patients at intervention hospitals, while maintaining accepted benchmarks for low rates of intracranial haemorrhage and high rates of functional outcomes for both groups at three months. METHODS AND DESIGN: A cluster randomised controlled trial of 20 hospitals across 3 Australian states with 2 groups: multi- component multidisciplinary collaborative intervention as the experimental group and usual care as the control group. The intervention is based on behavioural theory and analysis of the steps, roles and barriers relating to rapid assessment for thrombolysis eligibility; it involves a comprehensive range of strategies addressing individual-level and system-level change at each site. The primary outcome is the difference in tPA rates between the two groups post-intervention. The secondary outcome is the proportion of tPA treated patients in both groups with good functional outcomes (modified Rankin Score (mRS <2) and the proportion with intracranial haemorrhage (mRS ≥2), compared to international benchmarks. DISCUSSION: TIPS will trial a comprehensive, multi-component and multidisciplinary collaborative approach to improving thrombolysis rates at multiple sites. The trial has the potential to identify methods for optimal care which can be implemented for stroke patients during the acute phase. Study findings will include barriers and solutions to effective thrombolysis implementation and trial outcomes will be published whether significant or not. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN1261300093979

Pain shared, pain halved? Cooperation as a coping strategy for innovation barriers

The paper analyses the relationship between the perception of barriers to innovation and the firm’s propensity to cooperate to mitigate their effect. First, we look at whether cooperation with research organizations or private firms is associated with experiencing different types of barriers, for example, financial constraints, lack of human capital or uncertain market demand. Second, we test whether experiencing several types of barriers simultaneously has a super-modular effect on the propensity to cooperate tout court, and the choice of cooperation partner. We find that having to face a single, specific constraint leads to firms ‘sharing the pain’ with cooperation partners—both research organization and other firms. However, the results of a super-modularity test show that having to cope with different barriers is a deterrent to establishing cooperation agreements, especially when firms lack finance, adequate skills and information on technology or markets. The paper adds to the innovation literature by identifying the factors associated with firms’ coping with different barriers by applying a selective cooperation strategy

Cycle-finite module categories

We describe the structure of module categories of finite dimensional algebras over an algebraically closed field for which the cycles of nonzero nonisomorphisms between indecomposable finite dimensional modules are finite (do not belong to the infinite Jacobson radical of the module category). Moreover, geometric and homological properties of these module categories are exhibited

Transferring research from a university to the United Kingdom National Health Service : The implications for impact

This is an Open Access article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.The aim of this article is to inform readers of the author's reflections on the experience of transferring universitybased research into the commercial sector, and of the processes and strategies employed when preparing for impact in so doing. Concepts for the transfer are illustrated by the author's reflection on aspects that arose during the birthing and subsequent start-up of a university spin-off, Pathways2Wellbeing, a form of reflection-on-action. This is the vehicle for the adaption required to transfer research into the delivery of a specialised clinic in the United Kingdom National Health Service for people with medically unexplained, persistent, bodily symptoms such as fibromyalgia, chronic fatigue and chronic pain. It is hoped that the article will provide readers with an insight into how knowledge transfer can take place through engagement with stakeholders to create an exchange of knowledges to result in impact on health service policy for service users, despite the challenges, and the enablers that facilitated this process. The reflections on the process of knowledge transfer and the implications for impact are underpinned by relevant theory.Peer reviewedFinal Published versio

Proximity Dimensions and Scientific Collaboration among Academic Institutions in Europe: The Closer, the Better?

The main objective of this paper is to examine the effect of various proximity dimensions (geographical, cognitive, institutional, organizational, social and economic) on academic scientific collaborations (SC). The data to capture SC consists of a set of co-authored articles published between 2006 and 2010 by universities located in EU-15, indexed by the Science Citation Index (SCI Expanded) of the ISI Web of Science database. We link this data to institution-level information provided by the EUMIDA dataset. Our final sample consists of 240,495 co-authored articles from 690 European universities that featured in both datasets. Additionally, we also retrieved data on regional R&D funding from Eurostat. Based on the gravital equation, we estimate several econometrics models using aggregated data from all disciplines as well as separated data for Chemistry & Chemical Engineering, Life Sciences and Physics & Astronomy. Our results provide evidence on the substantial role of geographical, cognitive, institutional, social and economic distance in shaping scientific collaboration, while the effect of organizational proximity seems to be weaker. Some differences on the relevance of these factors arise at discipline level

Born to be green: new insights into the economics and management of green entrepreneurship

While the number of green start-ups has steadily increased around the world in response to the environmental problems demanding immediate solutions, there are several unresolved questions on the behaviour and performance of such ventures. The papers in this special issue shed light on these issues by underscoring the role of several factors, such as industry life cycles, knowledge spillovers, institutions, and availability of external finance, in shaping decision-making and firm behaviour in green start-ups. This paper highlights the state-of-the art developments in the literature, discusses the key contributions of the papers put together in this special issue and presents a future research agenda for scholars interested in green entrepreneurship