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

Autoantibodies against NMDA receptor 1 modify rather than cause encephalitis

The etiology and pathogenesis of “anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis” and the role of autoantibodies (AB) in this condition are still obscure. While NMDAR1-AB exert NMDAR-antagonistic properties by receptor internalization, no firm evidence exists to date that NMDAR1-AB by themselves induce brain inflammation/encephalitis. NMDAR1-AB of all immunoglobulin classes are highly frequent across mammals with multiple possible inducers and boosters. We hypothesized that “NMDAR encephalitis” results from any primary brain inflammation coinciding with the presence of NMDAR1-AB, which may shape the encephalitis phenotype. Thus, we tested whether following immunization with a “cocktail” of 4 NMDAR1 peptides, induction of a spatially and temporally defined sterile encephalitis by diphtheria toxin-mediated ablation of pyramidal neurons (“DTA” mice) would modify/aggravate the ensuing phenotype. In addition, we tried to replicate a recent report claiming that immunizing just against the NMDAR1-N368/G369 region induced brain inflammation. Mice after DTA induction revealed a syndrome comprising hyperactivity, hippocampal learning/memory deficits, prefrontal cortical network dysfunction, lasting blood brain-barrier impairment, brain inflammation, mainly in hippocampal and cortical regions with pyramidal neuronal death, microgliosis, astrogliosis, modest immune cell infiltration, regional atrophy, and relative increases in parvalbumin-positive interneurons. The presence of NMDAR1-AB enhanced the hyperactivity (psychosis-like) phenotype, whereas all other readouts were identical to control-immunized DTA mice. Non-DTA mice with or without NMDAR1-AB were free of any encephalitic signs. Replication of the reported NMDAR1-N368/G369-immunizing protocol in two large independent cohorts of wild-type mice completely failed. To conclude, while NMDAR1-AB can contribute to the behavioral phenotype of an underlying encephalitis, induction of an encephalitis by NMDAR1-AB themselves remains to be proven

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

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

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

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

Anesthesia triggers drug delivery to experimental glioma in mice by hijacking caveolar transport

Abstract Background: Pharmaceutical intervention in the CNS is hampered by the shielding function of the blood-brain barrier (BBB). To induce clinical anesthesia, general anesthetics such as isoflurane readily penetrate the BBB. Here, we investigated whether isoflurane can be utilized for therapeutic drug delivery. Methods: Barrier function in primary endothelial cells was evaluated by transepithelial/transendothelial electrical resistance, and nanoscale STED and SRRF microscopy. In mice, BBB permeability was quantified by extravasation of several fluorescent tracers. Mouse models including the GL261 glioma model were evaluated by MRI, immunohistochemistry, electron microscopy, western blot, and expression analysis. Results: Isoflurane enhances BBB permeability in a time- and concentration-dependent manner. We demonstrate that, mechanistically, isoflurane disturbs the organization of membrane lipid nanodomains and triggers caveolar transport in brain endothelial cells. BBB tightness re-establishes directly after termination of anesthesia, providing a defined window for drug delivery. In a therapeutic glioblastoma trial in mice, simultaneous exposure to isoflurane and cytotoxic agent improves efficacy of chemotherapy. Conclusions: Combination therapy, involving isoflurane-mediated BBB permeation with drug administration has far-reaching therapeutic implications for CNS malignancies

Platelet rich plasma injection grafts for musculoskeletal injuries: a review

In Europe and the United States, there is an increasing prevalence of the use of autologous blood products to facilitate healing in a variety of applications. Recently, we have learned more about specific growth factors, which play a crucial role in the healing process. With that knowledge there is abundant enthusiasm in the application of concentrated platelets, which release a supra-maximal quantity of these growth factors to stimulate recovery in non-healing injuries. For 20 years, the application of autologous PRP has been safely used and documented in many fields including; orthopedics, sports medicine, dentistry, ENT, neurosurgery, ophthalmology, urology, wound healing, cosmetic, cardiothoracic, and maxillofacial surgery. This article introduces the reader to PRP therapy and reviews the current literature on this emerging treatment modality. In summary, PRP provides a promising alternative to surgery by promoting safe and natural healing. However, there are few controlled trials, and mostly anecdotal or case reports. Additionally the sample sizes are frequently small, limiting the generalization of the findings. Recently, there is emerging literature on the beneficial effects of PRP for chronic non-healing tendon injuries including lateral epicondylitis and plantar fasciitis and cartilage degeneration (Mishra and Pavelko, The American Journal of Sports Medicine 10(10):1–5, 2006; Barrett and Erredge, Podiatry Today 17:37–42, 2004). However, as clinical use increases, more controlled studies are needed to further understand this treatment

Mite species inhabiting commercial bumblebee (Bombus terrestris) nests in Polish greenhouses

Nests of social insects are usually inhabited by various mite species that feed on pollen, other micro-arthropods or are parasitic. Well-known negative effects of worldwide economic importance are caused by mites parasitizing honeybee colonies. Lately, attention has focused on the endoparasitic mite Locustacarus buchneri that has been found in commercial bumblebees. However, little is known of other mites associated with commercial bumblebee nests. Transportation of commercial bumblebee colonies with unwanted residents may introduce foreign mite species to new localities. In this study, we assessed the prevalence and species composition of mites associated with commercial bumblebee nests and determined if the mites are foreign species for Poland and for Europe. The study was conducted on 37 commercial bumblebee nests from two companies (Dutch and Israeli), originating from two greenhouses in southern Poland, and on 20 commercial bumblebee colonies obtained directly from suppliers. The species composition and abundance of mites inhabiting commercial bumblebee nests were determined. Seven mite species from three families were found in nests after greenhouse exploitation. The predominant mite species was Tyrophagus putrescentiae (Acaridae) that was a 100-fold more numerous than representatives of the family Laelapidae (Hypoaspis marginepilosa, H. hyatti, H. bombicolens). Representatives of Parasitidae (Parasitellus fucorum, P. crinitus, P. ignotus) were least numerous. All identified mite species are common throughout Europe, foreign species were not found. Mites were not detected in nests obtained directly from suppliers. We conclude that probably bumblebee nests are invaded by local mite species during greenhouse exploitation