1,163 research outputs found
The Brain Microvascular Endothelium Supports T Cell Proliferation and Has Potential for Alloantigen Presentation
Endothelial cells (EC) form the inner lining of blood vessels and are positioned between circulating lymphocytes and tissues. Hypotheses have formed that EC may act as antigen presenting cells based on the intimate interactions with T cells, which are seen in diseases like multiple sclerosis, cerebral malaria (CM) and viral neuropathologies. Here, we investigated how human brain microvascular EC (HBEC) interact with and support the proliferation of T cells. We found HBEC to express MHC II, CD40 and ICOSL, key molecules for antigen presentation and co-stimulation and to take up fluorescently labeled antigens via macropinocytosis. In co-cultures, we showed that HBEC support and promote the proliferation of CD4+ and CD8+ T cells, which both are key in CM pathogenesis, particularly following T cell receptor activation and co-stimulation. Our findings provide novel evidence that HBEC can trigger T cell activation, thereby providing a novel mechanism for neuroimmunological complications of infectious diseases. © 2013 Wheway et al
On the Orthogonal Stability of the Pexiderized Quadratic Equation
The Hyers--Ulam stability of the conditional quadratic functional equation of
Pexider type f(x+y)+f(x-y)=2g(x)+2h(y), x\perp y is established where \perp is
a symmetric orthogonality in the sense of Ratz and f is odd.Comment: 10 pages, Latex; Changed conten
Formation of the simplest amide in molecular clouds: formamide (NHCHO) and its derivatives in HO-rich and CO-rich interstellar ice analogs upon VUV irradiation
The astronomical detection of formamide (NHCHO) toward various
star-forming regions and in cometary material implies that the simplest amide
might have an early origin in dark molecular clouds at low temperatures.
Laboratory studies have proven the efficient NHCHO formation in
interstellar CO:NH ice analogs upon energetic processing. However, it is
still under debate, whether the proposed radical-radical recombination
reactions forming complex organic molecules remain valid in an abundant HO
environment. The aim of this work was to investigate the formation of NHCHO
in HO- and CO-rich ices under conditions prevailing in molecular clouds.
Therefore, different ice mixtures composed of HO:CO:NH (10:5:1),
CO:NH (4:1), and CO:NH (0.6:1) were exposed to vacuum ultraviolet
photons in an ultra-high vacuum chamber at 10 K. Fourier-transform infrared
spectroscopy was utilized to monitor in situ the initial and newly formed
species as a function of photon fluence. The infrared spectral identifications
are complementarily secured by a temperature-programmed desorption experiment
combined with a quadrupole mass spectrometer. The energetic processing of
CO:NH ice mixtures mainly leads to the NHCHO formation, along with its
chemical derivatives such as isocyanic acid (HNCO) and cyanate ion (OCN).
The formation kinetics of NHCHO shows an explicit dependency on ice ratios
and compositions; the highest yield is found in HO-rich ice. The
astronomical relevance of the resulting reaction network is discussed.Comment: 16 pages, 6 figures, 2 table
Cerebral malaria: Gamma-interferon redux
There are two theories that seek to explain the pathogenesis of cerebral malaria, the mechanical obstruction hypothesis and the immunopathology hypothesis. Evidence consistent with both ideas has accumulated from studies of the human disease and experimental models. Thus, some combination of these concepts seems necessary to explain the very complex pattern of changes seen in cerebral malaria. The interactions between malaria parasites, erythrocytes, the cerebral microvascular endothelium, brain parenchymal cells, platelets and microparticles need to be considered. One factor that seems able to knit together much of this complexity is the cytokine interferon-gamma (IFN-?). In this review we consider findings from the clinical disease, in vitro models and the murine counterpart of human cerebral malaria in order to evaluate the roles played by IFN-? in the pathogenesis of this often fatal and debilitating condition. © 2014 Hunt, Ball, Hansen, Khaw, Guo, Bakmiwewa, Mitchell, Combes and Grau
Phi-values in protein folding kinetics have energetic and structural components
Phi-values are experimental measures of how the kinetics of protein folding
is changed by single-site mutations. Phi-values measure energetic quantities,
but are often interpreted in terms of the structures of the transition state
ensemble. Here we describe a simple analytical model of the folding kinetics in
terms of the formation of protein substructures. The model shows that
Phi-values have both structural and energetic components. In addition, it
provides a natural and general interpretation of "nonclassical" Phi-values
(i.e., less than zero, or greater than one). The model reproduces the
Phi-values for 20 single-residue mutations in the alpha-helix of the protein
CI2, including several nonclassical Phi-values, in good agreement with
experiments.Comment: 15 pages, 3 figures, 1 tabl
Patient-Reported Outcomes in ATLAS and FLAIR Participants on Long-Acting Regimens of Cabotegravir and Rilpivirine Over 48 Weeks
The phase 3 ATLAS and FLAIR studies demonstrated that maintenance with Long-Acting (LA) intramuscular cabotegravir and rilpivirine is non-inferior in efficacy to current antiretroviral (CAR) oral therapy. Both studies utilized Patient-Reported Outcome instruments to measure treatment satisfaction (HIVTSQ) and acceptance (ACCEPT general domain), health status (SF-12), injection tolerability/acceptance (PIN), and treatment preference. In pooled analyses, LA-treated patients (n = 591) demonstrated greater mean improvements from baseline than the CAR group (n = 591) in treatment satisfaction (Week 44, + 3.9 vs. +0.5 HIVTSQs-points; p /= 97% of LA group participants with recorded data preferred LA treatment compared with prior oral therapy. These results further support the potential of a monthly injectable option for people living with HIV seeking an alternative to daily oral treatment
Environmental variability in aquatic ecosystems: avenues for future multifactorial experiments
The relevance of considering environmental variability for understanding and predicting biological responses to environmental changes has resulted in a recent surge in variability-focused ecological research. However, integration of findings that emerge across studies and identification of remaining knowledge gaps in aquatic ecosystems remain critical. Here, we address these aspects by: (1) summarizing relevant terms of variability research including the components (characteristics) of variability and key interactions when considering multiple environmental factors; (2) identifying conceptual frameworks for understanding the consequences of environmental variability in single and multi-factorial scenarios; (3) highlighting challenges for bridging theoretical and experimental studies involving transitioning from simple to more complex scenarios; (4) proposing improved approaches to overcome current mismatches between theoretical predictions and experimental observations; and (5) providing a guide for designing integrated experiments across multiple scales, degrees of control, and complexity in light of their specific strengths and limitations
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