Glycosaminoglycan profile in macrophages exposed to Candida albicans and interleukins

Glycosaminoglycans (GAG), are extracellular matrix macromolecules that affect the phagocytic properties of macrophages. In order to assess whether the interaction between macrophages and Candida albicans (iCa) provokes changes in the phenotype, we analyzed the GAG profiles in two macrophage lines, ANA-1 (from murine bone-marrow) and BV-2 (from murine brain). We also investigated GAG modulation by interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6). During iCa treatment and even after the addition of ILs, ANA-1 accumulated less total GAG compared to controls. IL-1 treatment, combined with iCa exposure, induced a decrease in heparan sulfate and chondroitin sulfate chains, and an increase in the hyaluronic acid percentage. IL-6 treatment, with or without iCa, decreased the hyaluronic acid/sulfated GAG ratio. The GAG pattern in BV-2 appears to be different to ANA-1 and iCa exposure does not induce any difference in total GAG. The inhibitory effect induced by ILs on GAG synthesis is less than that observed in ANA-1 and the GAG elution profile is modulated to a lesser extent by treatment with ILs and/or iCa compared to the ANA-1. We suggest that the observed changes in the expression of the individual GAG classes may be responsible for the macrophage functional heterogeneity

Spin Stabilization of an Air Ambulance Litter

This paper proposes a new approach to stabilize the spin of a suspended litter during air ambulance rescue hoist operations. Complex forces generated by the helicopter’s downwash may cause a patient suspended in a rescue litter to spin violently. In severe cases, the spin destabilizes the suspended load, risks injury to the patient, and jeopardizes the safety of the aircrew. The presented design employs an anti-torque device to arrest the spin that is safer and faster than a tagline and is without the tactical constraints of the tagline. The device follows tailored control laws to accelerate a flywheel attached to the litter, thereby generating sufficient angular momentum to counteract the spin and stabilize the suspended litter. An inertial measurement unit (IMU) measures the position, angular velocity, and angular acceleration of the litter and delivers this information to a microcontroller. The research and prototype design were developed under the support of the U.S. Army 160th Special Operations Aviation Regiment (SOAR)

Geraniol Treatment for Irritable Bowel Syndrome: A Double-Blind Randomized Clinical Trial

Geraniol is an acyclic monoterpene alcohol with well-known anti-inflammatory and antimicrobial properties which has shown eubiotic activity towards gut microbiota (GM) in patients with irritable bowel syndrome (IBS). Methods: Fifty-six IBS patients diagnosed according to Rome III criteria were enrolled in an interventional, prospective, multicentric, randomized, double-blinded, placebo-controlled trial. In the treatment arm, patients received a low-absorbable geraniol food supplement (LAGS) once daily for four weeks. Results: Patients treated with LAGS showed a significant reduction in their IBS symptoms severity score (IBS-SSS) compared to the placebo (195 vs. 265, p = 0.001). The rate of responders according to IBS-SSS (reduction ≥ 50 points) was significantly higher in the geraniol vs placebo group (52.0% vs. 16.7%, p = 0.009) mainly due to the IBS mixed subtype. There were notable differences in the microbiota composition after geraniol administration, particularly a significant decrease in a genus of Ruminococcaceae, Oscillospira (p = 0.01), a decreasing trend for the Erysipelotrichaceae and Clostridiaceae families (p = 0.1), and an increasing trend for other Ruminococcaceae taxa, specifically Faecalibacterium (p = 0.09). The main circulating proinflammatory cytokines showed no differences between placebo and geraniol arms. Conclusion: LAGS was effective in treating overall IBS symptoms, together with an improvement in the gut microbiota profile, especially for the IBS mixed subtype

Visual Localization in the Presence of Appearance Changes Using the Partial Order Kernel

Visual localization across seasons and under varying weather and lighting conditions is a challenging task in robotics. In this paper, we present a new sequence-based approach to visual localization using the Partial Order Kernel (POKer), a convolution kernel for string comparison, that is able to handle appearance changes and is robust to speed variations. We use multiple sequence alignment to construct directed acyclic graph representations of the database image sequences, where sequences of images of the same place acquired at different times are represented as alternative paths in a graph. We then use the POKer to compute the pairwise similarities between these graphs and the query image sequences obtained in a subsequent traversal of the environment, and match the corresponding locations. We evaluated our approach on a dataset which features extreme appearance variations due to seasonal changes. The results demonstrate the effectiveness of our approach, where it achieves higher precision and recall than two state-of-the-art baseline method

Genetic susceptibility to aspergillosis in allogeneic stem-cell transplantation

Invasive aspergillosis (IA) is a major threat to positive outcomes for allogeneic stem-cell transplantation (allo-SCT) patients. Despite presenting similar degrees of immunosuppression, not all individuals at-risk ultimately develop infection. Therefore, the traditional view of neutropenia as a key risk factor for aspergillosis needs to be accommodated within new conceptual advances on host immunity and its relationship to infection. Polymorphisms in innate immune genes, such as those encoding TLRs, cytokines and cytokine receptors, have recently been associated with susceptibility to IA in allo-SCT recipients. This suggests that understanding host-pathogen interactions at the level of host genetic susceptibility will allow the formulation of new targeted and patient-tailored antifungal therapeutics, including improved donor screening.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/65962/2009, SFRH/BPD/46292/2008Specific Targeted Research Projects MANASP (LSHE-CT-2006), contract number 037899 (FP6), Italian Project PRIN2007KLCKP8_004

Control of a hippocampal recurrent excitatory circuit by cannabinoid receptor-interacting protein Gap43

The type-1 cannabinoid receptor (CB1R) is widely expressed in excitatory and inhibitory nerve terminals, and by suppressing neurotransmitter release, its activation modulates neural circuits and brain function. While the interaction of CB1R with various intracellular proteins is thought to alter receptor signaling, the identity and role of these proteins are poorly understood.Using a highthroughput proteomic analysis complemented with an array of in vitro and in vivo approaches in the mouse brain, we report that the C-terminal, intracellular domain of CB1R interacts specifically with growth-associated protein of 43 kDa (GAP43). The CB1R-GAP43 interaction occurs selectively at mossy cell axon boutons, which establish excitatory synapses with dentate granule cells in the hippocampus. This interaction impairs CB1R-mediated suppression of mossy cell to granule cell transmission, thereby inhibiting cannabinoidmediated anti-convulsant activity inmice. Thus, GAP43 acts as a synapse typespecific regulatory partner of CB1R that hampers CB1R-mediated effects on hippocampal circuit function

The endocannabinoid system controls food intake via olfactory processes

Comment in Sensory systems: the hungry sense. [Nat Rev Neurosci. 2014] Inhaling: endocannabinoids and food intake. [Nat Neurosci. 2014]; International audience; Hunger arouses sensory perception, eventually leading to an increase in food intake, but the underlying mechanisms remain poorly understood. We found that cannabinoid type-1 (CB1) receptors promote food intake in fasted mice by increasing odor detection. CB1 receptors were abundantly expressed on axon terminals of centrifugal cortical glutamatergic neurons that project to inhibitory granule cells of the main olfactory bulb (MOB). Local pharmacological and genetic manipulations revealed that endocannabinoids and exogenous cannabinoids increased odor detection and food intake in fasted mice by decreasing excitatory drive from olfactory cortex areas to the MOB. Consistently, cannabinoid agonists dampened in vivo optogenetically stimulated excitatory transmission in the same circuit. Our data indicate that cortical feedback projections to the MOB crucially regulate food intake via CB1 receptor signaling, linking the feeling of hunger to stronger odor processing. Thus, CB1 receptor-dependent control of cortical feedback projections in olfactory circuits couples internal states to perception and behavior

CB1 Signaling in Forebrain and Sympathetic Neurons Is a Key Determinant of Endocannabinoid Actions on Energy Balance

SummaryThe endocannabinoid system (ECS) plays a critical role in obesity development. The pharmacological blockade of cannabinoid receptor type 1 (CB1) has been shown to reduce body weight and to alleviate obesity-related metabolic disorders. An unsolved question is at which anatomical level CB1 modulates energy balance and the mechanisms involved in its action. Here, we demonstrate that CB1 receptors expressed in forebrain and sympathetic neurons play a key role in the pathophysiological development of diet-induced obesity. Conditional mutant mice lacking CB1 expression in neurons known to control energy balance, but not in nonneuronal peripheral organs, displayed a lean phenotype and resistance to diet-induced obesity. This phenotype results from an increase in lipid oxidation and thermogenesis as a consequence of an enhanced sympathetic tone and a decrease in energy absorption. In conclusion, CB1 signaling in the forebrain and sympathetic neurons is a key determinant of the ECS control of energy balance

Presence of extracellular DNA in the Candida albicans biofilm matrix and its contribution to biofilms

DNA has been described as a structural component of the extracellular matrix (ECM) in bacterial biofilms. In Candida albicans, there is a scarce knowledge concerning the contribution of extracellular DNA (eDNA) to biofilm matrix and overall structure. This work examined the presence and quantified the amount of eDNA in C. albicans biofilm ECM and the effect of DNase treatment and the addition of exogenous DNA on C. albicans biofilm development as indicators of a role for eDNA in biofilm development. We were able to detect the accumulation of eDNA in biofilm ECM extracted from C. albicans biofilms formed under conditions of flow, although the quantity of eDNA detected differed according to growth conditions, in particular with regards to the medium used to grow the biofilms. Experiments with C. albicans biofilms formed statically using a microtiter plate model indicated that the addition of exogenous DNA (>160 ng/ml) increases biofilm biomass and, conversely, DNase treatment (>0.03 mg/ml) decreases biofilm biomass at later time points of biofilm development. We present evidence for the role of eDNA in C. albicans biofilm structure and formation, consistent with eDNA being a key element of the ECM in mature C. albicans biofilms and playing a predominant role in biofilm structural integrity and maintenance.National Institute of Dental & Craniofacial ResearchFundação para a Ciência e Tecnologia (FCT) - SFRH/BD/28222/2006National Institute of Allergy and Infectious Disease