Synthesis and Characterization of Ceramide-Containing Liposomes as Membrane Models for Different T Cell Subpopulations

A fine balance of regulatory (Treg) and conventional CD4+ T cells (Tconv) is required to prevent harmful immune responses, while at the same time ensuring the development of protective immunity against pathogens. As for many cellular processes, sphingolipid metabolism also crucially modulates the Treg/Tconv balance. However, our understanding of how sphingolipid metabolism is involved in T cell biology is still evolving and a better characterization of the tools at hand is required to advance the field. Therefore, we established a reductionist liposomal membrane model system to imitate the plasma membrane of mouse Treg and Tconv with regards to their ceramide content. We found that the capacity of membranes to incorporate externally added azide-functionalized ceramide positively correlated with the ceramide content of the liposomes. Moreover, we studied the impact of the different liposomal preparations on primary mouse splenocytes in vitro. The addition of liposomes to resting, but not activated, splenocytes maintained viability with liposomes containing high amounts of C16-ceramide being most efficient. Our data thus suggest that differences in ceramide post-incorporation into Treg and Tconv reflect differences in the ceramide content of cellular membranes

Phytic acid against clostridium perfringens type a: a food matrix study

This study evaluated the inhibitory effect of phytic acid (PA) on the spore germination and vegetative cells growth of Clostridium perfringens type A, as well as its effect in combination with maltodextrin (MD) in cooked sausages. The addition of 1% PA showed a satisfactory inhibition of spores’ germination and vegetative cells growth of C. perfringens in BHI media. The inhibitory effect of 1% PA on vegetative cells was similar to the additive sodium sorbate (SS) at 10%. Subsequently, a mixture of PA-MD (1:1; w/w) was evaluated for the inhibition of C. perfringens spores in cooked sausages. The PA-MD 1.5% and 2.5% had a similar performance to SS 10% and a similar or higher performance than 0.015% NO2 (p < 0.05). In an unprecedented way, the present study demonstrated that PA inhibited spore germination and vegetative cells growth of C. perfringens, highlighting its potential use as an alternative and natural preservative for the meat industry.This research was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES)-Finance Code 001, Conselho Nacional de Desenvolvimento Científico e Tecnológico-Brazil (CNPq), and Fundação Araucária-Brazil-Programa Universal Pesquisa Básica e Aplicada (Edital 05/2011, Agreement 346/2014). J.S. Amaral is grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support by national funds FCT/MCTES to CIMO (UIDB/00690/2020).info:eu-repo/semantics/publishedVersio

Peeling graphite layer by layer reveals the charge exchange dynamics of ions inside a solid

Over seventy years ago, Niels Bohr described how the charge state of an atomic ion moving through a solid changes dynamically as a result of electron capture and loss processes, eventually resulting in an equilibrium charge state. Although obvious, this process has so far eluded direct experimental observation. By peeling a solid, such as graphite, layer by layer, and studying the transmission of highly charged ions through single-, bi- and trilayer graphene, we can now observe dynamical changes in ion charge states with monolayer precision. In addition we present a first-principles approach based on the virtual photon model for interparticle energy transfer to corroborate our findings. Our model that uses a Gaussian shaped dynamic polarisability rather than a spatial delta function is a major step in providing a self-consistent description for interparticle de-excitation processes at the limit of small separations

Peeling graphite layer by layer reveals the charge exchange dynamics of ions inside a solid

Over seventy years ago, Niels Bohr described how the charge state of an atomic ion moving through a solid changes dynamically as a result of electron capture and loss processes, eventually resulting in an equilibrium charge state. Although obvious, this process has so far eluded direct experimental observation. By peeling a solid, such as graphite, layer by layer, and studying the transmission of highly charged ions through single-, bi- and trilayer graphene, we can now observe dynamical changes in ion charge states with monolayer precision. In addition we present a first-principles approach based on the virtual photon model for interparticle energy transfer to corroborate our findings. Our model that uses a Gaussian shaped dynamic polarisability rather than a spatial delta function is a major step in providing a self-consistent description for interparticle de-excitation processes at the limit of small separations

A taxonomy of online syndicates

Thesis: S.M., Massachusetts Institute of Technology, Sloan School of Management, 2015.Cataloged from PDF version of thesis.Includes bibliographical references (pages 73-76).New businesses financing has evolved over the years from closed-end funds to limited partnership financing, angel investing and the most current form of online syndication. While VC financing has been covered thoroughly from financing and behavioral perspectives in research, very little is known about online syndicates which have appeared in recent years with the creation of AngelList. This paper's objective is to establish a first taxonomy of the most active angel syndicates at the time this research was conducted. Based on characteristics related to work experience, education and reputation this paper presents a systematic overview of these syndicates' founders, where they have studied and worked, how well-known they are in social media and how their investments have performed. By dividing the data into quartiles according to total funding raised and number of backers attracted, I find astonishing differences across the quartiles for certain variables while others are rather inconclusive. Education and work experience (e.g. consulting, IB, VC, etc.) as well as years spent as entrepreneurs and investors do not show a clear relationship with the number of backers or total funding a lead is able to attain. Number of startups founded, number of acquisition exits, Twitter followers and Google search results, however, seem to explain 36% of the variation of total funding raised and 43% of the variation in the number of backers. The findings suggest that despite a large heterogeneity in syndicate lead characteristics, those successful at raising high amounts of funding and attracting many backers share common traits.by Sascha Jan Eder.S.M

Imitation of action-effects increases social affiliation

Imitating someone's actions influences social-affective evaluations and motor performance for the action model and the imitator alike. Both phenomena are explained by the similarity between the sensory and motor representations of the action. Importantly, however, theoretical accounts of action control hold that actions are represented in terms of their sensory effects, which encompass features of the movement but also features of an action's consequence in the outside world. This suggests that social-affective consequences of imitation should not be limited to situations in which the imitator copies the model's body movements. Rather, the present study tested whether copying the perceived action-effects of another person without imitating the eventual body movements increases the social-affective evaluation of this person. In three experiments, participants produced visual action-effects while observing videos of models who performed either the same or a different movement and produced either the same or a different action-effect. If instructions framed the action in terms of the movement, participants preferred models with similar movements (Experiment 1). However, if instructions framed the action in terms of the to-be produced action-effect in the environment, participants preferred models with similar action-effects (Experiments 2 and 3). These results extend effect-based accounts of action control like the ideomotor framework and suggest a close link between action control and affective processing in social interactions

Clinics / Experience in Intra-arterial Chemotherapy using Two Protocols for the Treatment of OSCC over Two Decades at the University Hospital Vienna

OBJECTIVES: This retrospective study performed a comprehensive analysis of the usage of intra-arterial chemotherapy (iaCh) for locally recurrent UICC stage IV oral squamous cell carcinoma (OSCC) over two decades at the Department of Cranio-Maxillofacial and Oral Surgery at the University Hospital Vienna to assess the utility of its future use. METHODS: Between 1994 and 2014, iaCh was indicated in 48 OSCC cases. In these, the two most frequent iaCh schemes, cisplatin/5-fluorouracil (Cis/5-FU) and methotrexate/bleomycin (MTX/Bleo), were chosen for further analysis. The effect on survival of two distinct intra-arterial protocols and their covariates were analyzed with the Kaplan-Meier method as well as univariate and multivariate Cox proportional hazard regression models. RESULTS: The mean follow-up period was 29.91 months. The two intra-arterial chemotherapy groups did not differ significantly in sample size, demographic data or therapeutic covariates. The Cis/5-FU iaCh regimen was associated with significantly better overall survival (median OS 2.6 years vs. 1.3 years; p=0.002) and had a beneficial effect on survival (HR=3.62, p=0.015). Side effects occurred at a frequency similar to that described in the literature for intravenous chemotherapy (ivCh). CONCLUSIONS: These results suggest a preference for administering Cis/5-FU for iaCh. Nevertheless, due to economic considerations in healthcare expenditures, there is no future for iaCh in the treatment of head and neck carcinomas because ivCh is known to be equivalent.(VLID)470944

Desipramine targets astrocytes to attenuate synaptic plasticity via modulation of the ephrinA3/EphA4 signalling

Long-term potentiation (LTP), a major cellular correlate of memory storage, depends on activation of the ERK/MAPK signalling pathway, but the cell type-specific localization of activated MAPKs remains unknown. We found that in the CM field of the hippocampus, shortly after LTP induction, an increase in the number of MAPK-positive cells occurred specifically among astrocytes of the stratum radiatum, suggesting a putative role of astrocytes for LTP. Desipramine (DMI) is an antidepressant which is used to treat major depressive disorder, but also other pathologies such as neuropathic pain or attention-deficit/hyperactivity disorder. Tricyclic antidepressants such as DMI may cause memory impairment as a side effect. However, biological underpinnings of this effect still remain unclear. Here, we show that DMI inhibited the astrocytic MAPK activation and thereby hindered synaptic potentiation. These effects correlated with a reduced neuronal activation in the stratum pyramidale, thereby prompting us to analyse a regulator of LTP located at the astrocyte-neuron interface in the stratum radiatum, namely the ephrinA3/EphA4 signalling pathway. DMI enhanced EphA4 clustering, which favoured an increased ephrinA3-mediated EphA4 phosphorylation and elevated EphA4 forward signalling. The co-administration of DMI with the Src inhibitor SU6656, which blocks EphA4 forward signalling, could partially reverse the LTP attenuation, further supporting the targeting of the ephrinA3/EphA4 pathway by DMI. Thus, our findings suggest a putative novel mechanism for DMI to modulate LTP through the regulation of the ephrinA3/EphA4 signalling pathway. A further exploration of the molecular and behavioral consequences of targeting ephrinA3/EphA4 might help to improve the clinical use of DMI. (C) 2016 Elsevier Ltd. All rights reserved

miR-125b regulates chemotaxis and survival of bone marrow derived granulocytes in vitro and in vivo.

The evolutionary conserved miR-125b is highly expressed in hematopoietic stem cells (HSC) enhancing self-renewal and survival. Accordingly, over-expression of miR-125b in HSC may induce myeloproliferative neoplasms and leukemia with long latency. During hematopoietic cell maturation miR-125b expression decreases, and the function of miR-125b in mature granulocytes is not yet known. We here use transplantation of miR-125b over-expressing HSC into syngeneic hosts to generate and analyse miR-125b over-expressing granulocytes. Under steady state conditions, miR-125b over-expression inhibits granulocytic chemotaxis and LPS- but not PMA- and TNFα- induced cell death. Inflammatory signals modulate the effects of miR-125b over-expression as demonstrated in a sterile peritonitis and a polymicrobial sepsis model. In particular, survival of mice with miR-125b over-expressing granulocytes is significantly reduced as compared to controls in the polymicrobial sepsis model. These data demonstrate inflammation dependent effects of miR-125b in granulocytes and may point to therapeutic intervention strategies in the future