Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

Drainage of central nervous system (CNS) antigens to the brain-draining cervical lymph nodes (CLN) is likely crucial in the initiation and control of autoimmune responses during multiple sclerosis (MS). We demonstrate neuronal antigens within CLN of MS patients. In monkeys and mice with experimental autoimmune encephalomyelitis (EAE) and in mouse models with non-inflammatory CNS damage, the type and extent of CNS damage was associated with the frequencies of CNS antigens within the cervical lymph nodes. In addition, CNS antigens drained to the spinal-cord-draining lumbar lymph nodes. In human MS CLN, neuronal antigens were present in pro-inflammatory antigen-presenting cells (APC), whereas the majority of myelin-containing cells were anti-inflammatory. This may reflect a different origin of the cells or different drainage mechanisms. Indeed, neuronal antigen-containing cells in human CLN did not express the lymph node homing receptor CCR7, whereas myelin antigen-containing cells in situ and in vitro did. Nevertheless, CLN from EAE-affected CCR7-deficient mice contained equal amounts of myelin and neuronal antigens as wild-type mice. We conclude that the type and frequencies of CNS antigens within the CLN are determined by the type and extent of CNS damage. Furthermore, the presence of myelin and neuronal antigens in functionally distinct APC populations within MS CLN suggests that differential immune responses can be evoked

Value of routine transpedicular biopsies in kyphoplasty and vertebroplasty for vertebral compression fractures: A survey among 250 spine surgeons

Zusammenfassung Hintergrund: Transpedikuläre Zementaugmentationen sind eine etablierte Therapieoption in der Behandlung pathologischer Kompressionsfrakturen der Wirbelsäule. Neben der Osteoporose sind auch immer wieder metastasierte Grundleiden oder seltener ein primärer Knochentumor Ursache für Wirbelkompressionsfrakturen ohne adäquates Trauma. Ziel: Erstellung eines aktuellen Meinungsbildes unter Wirbelsäulenchirurgen in Deutschland, der Schweiz und Österreich zum Stellenwert der transpedikulären Biopsie während Kypho- und Vertebroplastien von Wirbelkörperfrakturen. Material und Methoden: Es wurde ein webbasierter UmfrageOnline®-Fragebogen mit 11 Fragen erstellt und an die E‑Mail-Verteiler der Deutschen Wirbelsäulengesellschaft (DWG), der Österreichischen Gesellschaft für Wirbelsäulenchirurgie (spine.at) und der Schweizerischen Gesellschaft für spinale Chirurgie (SGS) sowie an den E‑Mail-Verteiler der Sektion Wirbelsäule der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie (DGOU) versendet. Ergebnisse: Von insgesamt kontaktierten 2675 Wirbelsäulenchirurgen beantworteten 250 (9,3 %) die Umfrage. Rund ein Drittel (29,8 %) der Befragten führt regelhaft bei jeder Kypho- oder Vertebroplastie eine transpedikuläre Biopsie durch. Genannte Gründe für eine Biopsie waren ein bildmorphologischer (79,7 %) oder anamnestischer Verdacht auf eine Tumorerkrankung (66,0 %) oder das Vorliegen einer solchen (71,4 %). Als Gründe gegen eine routinemäßige Biopsie wurden die damit verbundenen Kosten und die limitierte Aussagekraft der gewonnenen Biopsate genannt. Diskussion: Fast ein Drittel der befragten Wirbelsäulenchirurgen führt regelhaft bei jeder Kypho- oder Vertebroplastie eine transpedikuläre Biopsie durch. Fast alle Befragten führen Biopsien zumindest dann durch, wenn eine Tumorerkrankung bekannt ist bzw. aufgrund von Risikofaktoren vermutet wird. Zukünftige Studien müssen die Kosteneffizienz der transpedikulären Biopsie weiter abklären.Abstract Background: Transpedicular cement augmentation is an established therapeutic option in the treatment of pathologic compression fractures of the spine. In addition to osteoporosis, underlying metastatic diseases or, more rarely, a primary bone tumor are recurrent causes of vertebral compression fractures without adequate trauma. Objective: To obtain a current opinion among spine surgeons in Germany, Switzerland, and Austria on the value of transpedicular biopsy during kyphoplasty and vertebroplasty of vertebral body fractures. Material and methods: A web-based (UmfrageOnline®) questionnaire with 11 questions was created and sent to the email distribution lists of the German Spine Society (DWG), the Austrian Society for Spine Surgery (spine.at), and the Swiss Society for Spinal Surgery (SGS), as well as to the email distribution list of the Spine Section of the German Society for Orthopedics and Trauma Surgery (DGOU). Results: Of a total of 2675 spine surgeons contacted 250 (9.3%) responded to the survey. Approximately one third (29.8%) of respondents regularly perform a transpedicular biopsy with each kyphoplasty or vertebroplasty. Reasons cited for biopsy were image morphology (79.7%) or history of suspected (66.0%) or present (71.4%) tumor disease. Reasons cited against routine biopsy were the associated costs and the limited informative value of the biopsies obtained. Discussion: Nearly one third of the spine surgeons surveyed regularly perform a transpedicular biopsy with each kyphoplasty or vertebroplasty. Almost all respondents perform biopsies at least when there is an imaging morphologic suspicion of tumor disease or tumor disease is known or suspected based on risk factors. Future studies need to further clarify the cost-effectiveness of transpedicular biopsy

Impact and the reflexive imperative in criminal justice policy, practice and research

This chapter is a substantive editorial introduction to the book, Reflexivity and Criminal Justice: Intersections of Policy, Practice and Research. It develops and argues for an account of reflexivity in criminology beyond the researcher-researched relationship to the field of research itself. Universities are under increasing pressure to document the value of their work, often defined instrumentally in terms of immediate practical and commercial activities. This has led to increasing emphasis on ‘partnerships’ and knowledge exchange with organisations and actors outside of academia. While such relationships may be empowering and supportive of good research and thriving societies, they also raise critical questions about agenda setting and valuation of social science. These questions become especially acute in a discipline such as criminology, with its attention to crime control, surveillance and state punishment, topics which can be co-opted by particular interests. We address the potential and risks of reflexivity in this setting, concluding that it might offer a stance that assists researchers in exposing the complicated dynamics of the conditions of criminal justice research in contemporary times. The content of the chapters comprising the book are summarised and woven into the discussion throughout this introduction

What happens in the Lab: Applying Midstream Modulation to Enhance Critical Reflection in the Laboratory

In response to widespread policy prescriptions for responsible innovation, social scientists and engineering ethicists, among others, have sought to engage natural scientists and engineers at the ‘midstream’: building interdisciplinary collaborations to integrate social and ethical considerations with research and development processes. Two ‘laboratory engagement studies’ have explored how applying the framework of midstream modulation could enhance the reflections of natural scientists on the socio-ethical context of their work. The results of these interdisciplinary collaborations confirm the utility of midstream modulation in encouraging both first- and second-order reflective learning. The potential for second-order reflective learning, in which underlying value systems become the object of reflection, is particularly significant with respect to addressing social responsibility in research practices. Midstream modulation served to render the socio-ethical context of research visible in the laboratory and helped enable research participants to more critically reflect on this broader context. While lab-based collaborations would benefit from being carried out in concert with activities at institutional and policy levels, midstream modulation could prove a valuable asset in the toolbox of interdisciplinary methods aimed at responsible innovation

Comparative transcriptome profiling of amyloid precursor protein family members in the adult cortex

<p>Abstract</p> <p>Background</p> <p>The β-amyloid precursor protein (APP) and the related β-amyloid precursor-like proteins (APLPs) undergo complex proteolytic processing giving rise to several fragments. Whereas it is well established that Aβ accumulation is a central trigger for Alzheimer's disease, the physiological role of APP family members and their diverse proteolytic products is still largely unknown. The secreted APPsα ectodomain has been shown to be involved in neuroprotection and synaptic plasticity. The γ-secretase-generated APP intracellular domain (AICD) functions as a transcriptional regulator in heterologous reporter assays although its role for endogenous gene regulation has remained controversial.</p> <p>Results</p> <p>To gain further insight into the molecular changes associated with knockout phenotypes and to elucidate the physiological functions of APP family members including their proposed role as transcriptional regulators, we performed DNA microarray transcriptome profiling of prefrontal cortex of adult wild-type (WT), APP knockout (APP^-/-), APLP2 knockout (APLP2^-/-) and APPsα knockin mice (APP^α/α) expressing solely the secreted APPsα ectodomain. Biological pathways affected by the lack of APP family members included neurogenesis, transcription, and kinase activity. Comparative analysis of transcriptome changes between mutant and wild-type mice, followed by qPCR validation, identified co-regulated gene sets. Interestingly, these included heat shock proteins and plasticity-related genes that were both down-regulated in knockout cortices. In contrast, we failed to detect significant differences in expression of previously proposed AICD target genes including <it>Bace1</it>, <it>Kai1</it>, <it>Gsk3b</it>, <it>p53</it>, <it>Tip60</it>, and <it>Vglut2</it>. Only <it>Egfr </it>was slightly up-regulated in APLP2^-/-mice. Comparison of APP^-/-and APP^α/αwith wild-type mice revealed a high proportion of co-regulated genes indicating an important role of the C-terminus for cellular signaling. Finally, comparison of APLP2^-/-on different genetic backgrounds revealed that background-related transcriptome changes may dominate over changes due to the knockout of a single gene.</p> <p>Conclusion</p> <p>Shared transcriptome profiles corroborated closely related physiological functions of APP family members in the adult central nervous system. As expression of proposed AICD target genes was not altered in adult cortex, this may indicate that these genes are not affected by lack of APP under resting conditions or only in a small subset of cells.</p

Counteranion and Solvent Assistance in Ruthenium-Mediated Alkyne to Vinylidene Isomerizations

The complex [Cp*RuCl(iPr2PNHPy)] (1) reacts with 1-alkynes HC≡CR (R = COOMe, C6H4CF3) in dichloromethane furnishing the corresponding vinylidene complexes [Cp*Ru≡C≡CHR(iPr2PNHPy)]Cl (R = COOMe (2a- Cl), C6H4CF3 (2b-Cl)), whereas reaction of 1 with NaBPh4 in MeOH followed by addition of HC≡CR (R = COOMe, C6H4CF3) yields the metastable π-alkyne complexes [Cp*Ru(η2-HC≡CR)(iPr2PNHPy)][BPh4] (R = COOMe (3a-BPh4), C6H4CF3 (3b-BPh4)). The transformation of 3a-BPh4/3b-BPh4 into their respective vinylidene isomers in dichloromethane is very slow and requires hours to its completion. However, this process is accelerated by addition of LiCl in methanol solution. Reaction of 1 with HC≡CR (R = COOMe, C6H4CF3) in MeOH goes through the intermediacy of the π-alkyne complexes [Cp*Ru(η2-HC≡CR)(iPr2PNHPy)]Cl (R = COOMe (3a-Cl), C6H4CF3 (3b-Cl)), which rearrange to vinylidenes in minutes, i.e., much faster than their counterparts containing the [BPh4]− anion. The kinetics of these isomerizations has been studied in solution by NMR. With the help of DFT studies, these observations have been interpreted in terms of chloride- and methanolassisted hydrogen migrations. Calculations suggest participation of a hydrido−alkynyl intermediate in the process, in which the hydrogen atom can be transferred from the metal to the β-carbon by means of species with weak basic character acting as proton shuttles

Neuronal Chemokines: Versatile Messengers In Central Nervous System Cell Interaction

Whereas chemokines are well known for their ability to induce cell migration, only recently it became evident that chemokines also control a variety of other cell functions and are versatile messengers in the interaction between a diversity of cell types. In the central nervous system (CNS), chemokines are generally found under both physiological and pathological conditions. Whereas many reports describe chemokine expression in astrocytes and microglia and their role in the migration of leukocytes into the CNS, only few studies describe chemokine expression in neurons. Nevertheless, the expression of neuronal chemokines and the corresponding chemokine receptors in CNS cells under physiological and pathological conditions indicates that neuronal chemokines contribute to CNS cell interaction. In this study, we review recent studies describing neuronal chemokine expression and discuss potential roles of neuronal chemokines in neuron–astrocyte, neuron–microglia, and neuron–neuron interaction

The role of war in deep transitions: exploring mechanisms, imprints and rules in sociotechnical systems

This paper explores in what ways the two world wars influenced the development of sociotechnical systems underpinning the culmination of the first deep transition. The role of war is an underexplored aspect in both the Techno-Economic Paradigms (TEP) approach and the Multi-level perspective (MLP) which form the two key conceptual building blocks of the Deep Transitions (DT) framework. Thus, we develop a conceptual approach tailored to this particular topic which integrates accounts of total war and mechanisms of war from historical studies and imprinting from organisational studies with the DT framework’s attention towards rules and meta-rules. We explore in what ways the three sociotechnical systems of energy, food, and transport were affected by the emergence of new demand pressures and logistical challenges during conditions of total war; how war impacted the directionality of sociotechnical systems; the extent to which new national and international policy capacities emerged during wartime in the energy, food, and transport systems; and the extent to which these systems were influenced by cooperation and shared sacrifice under wartime conditions. We then explore what lasting changes were influenced by the two wars in the energy, food, and transport systems across the transatlantic zone. This paper seeks to open up a hitherto neglected area in analysis on sociotechnical transitions and we discuss the importance of further research that is attentive towards entanglements of warfare and the military particularly in the field of sustainability transitions