Photopolymerizable platelet lysate hydrogels for customizable 3D cell culture platforms

3D cell culture platforms have emerged as a setting that resembles in vivo environments replacing the traditional 2D platforms. Over the recent years, an extensive effort has been made on the development of more physiologically relevant 3D cell culture platforms. Extracellular matrix-based materials have been reported as a bioactive and biocompatible support for cell culture. For example, human plasma derivatives have been extensively used in cell culture. Despite all the promising results, in most cases these types of materials have poor mechanical properties and poor stability in vitro. Here plasma-based hydrogels with increased stability are proposed. Platelet lysates are modified by addition of methacryloyl groups (PLMA) that polymerize in controlled geometries upon UV light exposure. The hydrogels could also generate porous scaffolds after lyophilization. The results show that PLMA materials have increased mechanical properties that can be easily adjusted by changing PLMA concentration or modification degree. Cells readily adhere, proliferate, and migrate, exhibiting high viability when encapsulated in PLMA hydrogels. The innovation potential of PLMA materials is based on the fact that it is a complete xeno-free solution for human cell culture, thus an effective alternative to the current gold standards for 3D cell culture based on animal products.publishe

Inducing sterile pyramidal neuronal death in mice to model distinct aspects of gray matter encephalitis

Up to one person in a population of 10,000 is diagnosed once in lifetime with an encephalitis, in 50–70% of unknown origin. Recognized causes amount to 20–50% viral infections. Approximately one third of affected subjects develops moderate and severe subsequent damage. Several neurotropic viruses can directly infect pyramidal neurons and induce neuronal death in cortex and hippocampus. The resulting encephalitic syndromes are frequently associated with cognitive deterioration and dementia, but involve numerous parallel and downstream cellular and molecular events that make the interpretation of direct consequences of sudden pyramidal neuronal loss difficult. This, however, would be pivotal for understanding how neuroinflammatory processes initiate the development of neurodegeneration, and thus for targeted prophylactic and therapeutic interventions. Here we utilized adult male NexCre‑ ERT2xRosa26-eGFP-DTA (= ‘DTA’) mice for the induction of a sterile encephalitis by diphtheria toxin-mediated ablation of cortical and hippocampal pyramidal neurons which also recruits immune cells into gray matter. We report multifaceted aftereffects of this defined process, including the expected pathology of classical hippocampal behaviors, evaluated in Morris water maze, but also of (pre)frontal circuit function, assessed by prepulse inhibition. Importantly, we modelled in encephalitis mice novel translationally relevant sequelae, namely altered social interaction/cognition, accompanied by compromised thermoreaction to social stimuli as convenient readout of parallel autonomic nervous system (dys)function. High resolution magnetic resonance imaging disclosed distinct abnormalities in brain dimensions, including cortical and hippocampal layering, as well as of cerebral blood flow and volume. Fluorescent tracer injection, immunohistochemistry and brain flow cytometry revealed persistent blood–brain-barrier perturbance and chronic brain inflammation. Surprisingly, blood flow cytometry showed no abnormalities in circulating major immune cell subsets and plasma high-mobility group box 1 (HMGB1) as proinflammatory marker remained unchanged. The present experimental work, analyzing multidimensional outcomes of direct pyramidal neuronal loss, will open new avenues for urgently needed encephalitis research

Army imposters:diversification of army ant-mimicking beetles with their Eciton hosts

Colonies of neotropical army ants of the genus Eciton Latreille offer some of the most captivating examples of intricate interactions between species, with hundreds of associated species already described in colonies of Eciton burchellii Westwood. Among this plethora of species found with Eciton colonies, two genera of staphylinid beetles, Ecitomorpha Wasmann, and Ecitophya Wasmann, have evolved to mimic the appearance and parallel the colouration of the most abundant ant worker cast. Here, we study for the first time the association of these ant-mimicking beetles with their ant host in an evolutionary and population genetics framework. The central emphasis is on colonies of E. burchellii, the only Eciton species that harbours both genera of ant-mimicking beetles. Phylogenetic and population structure analyses using the same mtDNA COI region (802 bp) for ants and beetles indicated that speciation patterns of the myrmecophiles were congruent with specialization to a particular Eciton (sub)species. Therefore, current taxonomic treatments of Eciton and its Ecitomorpha and Ecitophya associates need revision. Molecular clock analyses suggested that diversification of the Eciton hosts pre-date that of their guests, with a possible earlier association of Ecitophya (found with a large number of Eciton species) than with Ecitomorpha (found only with E. burchellii colonies). Population-level analyses revealed that patterns of diversification for the myrmecophiles are also consistent with specialisation to a particular host across broad geographical areas but not at small geographical scales, with gene flow within each species found between host colonies, even across landscape features that are strong barriers for Eciton female-mediated gene flow

Large-scale database mining reveals hidden trends and future directions for cancer immunotherapy

LLC Cancer immunotherapy has fundamentally changed the landscape of oncology in recent years and significant resources are invested into immunotherapy research. It is in the interests of researchers and clinicians to identify promising and less promising trends in this field in order to rationally allocate resources. This requires a quantitative large-scale analysis of cancer immunotherapy related databases. We developed a novel tool for text mining, statistical analysis and data visualization of scientific literature data. We used this tool to analyze 72002 cancer immunotherapy publications and 1469 clinical trials from public databases. All source codes are available under an open access license. The contribution of specific topics within the cancer immunotherapy field has markedly shifted over the years. We show that the focus is moving from cell-based therapy and vaccination towards checkpoint inhibitors, with these trends reaching statistical significance. Rapidly growing subfields include the combination of chemotherapy with checkpoint blockade. Translational studies have shifted from hematological and skin neoplasms to gastrointestinal and lung cancer and from tumor antigens and angiogenesis to tumor stroma and apoptosis. This work highlights the importance of unbiased large-scale database mining to assess trends in cancer research and cancer immunotherapy in particular. Researchers, clinicians and funding agencies should be aware of quantitative trends in the immunotherapy field, allocate resources to the most promising areas and find new approaches for currently immature topics

Dietary cholesterol promotes repair of demyelinated lesions in the adult brain

Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes

Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP: a new disease entity?

BACKGROUND: Human prion diseases are a group of rare fatal neurodegenerative conditions with well-developed clinical and neuropathological diagnostic criteria. Recent observations have expanded the spectrum of prion diseases beyond the classically recognized forms. RESULTS: In the present study we report six patients with a novel, apparently sporadic disease characterised by thalamic degeneration and rapidly progressive dementia (duration of illness 2-12 months; age at death: 55-81 years). Light and electron microscopic immunostaining for the prion protein (PrP) revealed a peculiar intraneuritic distribution in neocortical regions. Proteinase K resistant PrP (PrPres) was undetectable by Western blotting in frontal cortex from the three cases with frozen tissue, even after enrichment for PrPres by centrifugation or by phosphotungstic acid precipitation. Conformation-dependent immunoassay analysis using a range of PK digestion conditions (and no PK digestion) produced only very limited evidence of meaningful D-N (denatured/native) values, indicative of the presence of disease-associated PrP (PrPSc) in these cases, when the results were compared with appropriate negative control groups. CONCLUSIONS: Our observation expands the spectrum of conditions associated with rapidly progressive dementia and may have implications for the understanding of the pathogenesis of prion diseases

Managerial power in the German model: the case of Bertelsmann and the antecedents of neoliberalism

Our article extends the research on authoritarian neoliberalism to Germany, through a history of the Bertelsmann media corporation – sponsor and namesake of Germany’s most influential neoliberal think-tank. Our article makes three conceptual moves. Firstly, we argue that conceptualizing German neoliberalism in terms of an ‘ordoliberal paradigm’ is of limited use in explaining the rise and fall of Germany’s distinctive socio-economic model (Modell Deutschland). Instead, we locate the origins of authoritarian tendencies in the corporate power exercised by managers rather than in the power of state-backed markets imagined by ordoliberals. Secondly, we focus on the managerial innovations of Bertelsmann as a key actor enmeshed with Modell Deutschland. We show that the adaptation of business management practices of an endogenous ‘Cologne School’ empowered Bertelsmann’s postwar managers to overcome existential crises and financial constraints despite being excluded from Germany’s corporate support network. Thirdly, we argue that their further development in the 1970s also enabled Bertelsmann to curtail and circumvent the forms of labour representation associated with Modell Deutschland. Inspired by cybernetic management theories that it used to limit and control rather than revive market competition among its workforce, Bertelsmann began to act and think outside the postwar settlement between capital and labour before the settlement’s hotly-debated demise since the 1990s

A λ-lemma for Normally Hyperbolic Invariant Manifolds

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Theory and simulation of quantum photovoltaic devices based on the non-equilibrium Green's function formalism

This article reviews the application of the non-equilibrium Green's function formalism to the simulation of novel photovoltaic devices utilizing quantum confinement effects in low dimensional absorber structures. It covers well-known aspects of the fundamental NEGF theory for a system of interacting electrons, photons and phonons with relevance for the simulation of optoelectronic devices and introduces at the same time new approaches to the theoretical description of the elementary processes of photovoltaic device operation, such as photogeneration via coherent excitonic absorption, phonon-mediated indirect optical transitions or non-radiative recombination via defect states. While the description of the theoretical framework is kept as general as possible, two specific prototypical quantum photovoltaic devices, a single quantum well photodiode and a silicon-oxide based superlattice absorber, are used to illustrated the kind of unique insight that numerical simulations based on the theory are able to provide.Comment: 20 pages, 10 figures; invited review pape

Effects of the Cryptochrome CryB from Rhodobacter sphaeroides on Global Gene Expression in the Dark or Blue Light or in the Presence of Singlet Oxygen

Several regulators are controlling the formation of the photosynthetic apparatus in the facultatively photosynthetic bacterium Rhodobacter sphaeroides. Among the proteins affecting photosynthesis gene expression is the blue light photoreceptor cryptochrome CryB. This study addresses the effect of CryB on global gene expression. The data reveal that CryB does not only influence photosynthesis gene expression but also genes for the non-photosynthetic energy metabolism like citric acid cycle and oxidative phosphorylation. In addition several genes involved in RNA processing and in transcriptional regulation are affected by a cryB deletion. Although CryB was shown to undergo a photocycle it does not only affect gene expression in response to blue light illumination but also in response to singlet oxygen stress conditions. While there is a large overlap in these responses, some CryB-dependent effects are specific for blue-light or photooxidative stress. In addition to protein-coding genes some genes for sRNAs show CryB-dependent expression. These findings give new insight into the function of bacterial cryptochromes and demonstrate for the first time a function in the oxidative stress response