The Role of Inflammation in Amyloid Diseases

Amyloid diseases are characterized by the abnormal accumulation of proteinaceous aggregates (amyloid fibrils or plaques) in tissues and organs. This class of diseases is also characterized by the presence of inflammation. Amyloid fibrils arise from the partial denaturing and unfolding of native proteins. The accumulation of amyloid fibrils causes tissue damage and elicits local and nonlocal immune cell infiltration into tissue and proinflammatory cytokine production. Moreover, these conditions fuel a vicious cycle that can increase amyloid production and create an environment of chronic inflammation. A chronically inflamed tissue rapidly deteriorates and loses its function. In this chapter, we will discuss important data gathered over the years describing the role of inflammation in amyloid diseases. We will describe how inflammation begins and how it affects disease progression for major amyloid diseases, such as Alzheimer’s disease (AD) and hereditary TTR amyloidosis (hATTR). Lastly, we will discuss the recent advancements in treatments for amyloid diseases and how they address inflammation in affected patients

Collider Bounds on Lee-Wick Higgs Bosons

We study the constraints on the Lee-Wick Higgs sector arising from direct collider searches. We work in an effective-field theory framework, where all of the Lee-Wick partners are integrated out, with the sole exception of the Lee-Wick Higgs bosons. The resulting theory is a two-Higgs doublet model where the second doublet has wrong-sign kinetic and mass terms. We include the bounds coming from direct Higgs searches at both LEP and Tevatron using the code HiggsBounds, and show the currently excluded parameter space. We also analyze the prospects of LHC Run-I, finding that with a total integrated luminosity of 5 fb $^{-1}$ and a center-of-mass energy of 7 TeV, most of the parameter space for the SM-like CP-even Higgs will be probed.Comment: 26 pages, 5 figures, matches version published by PR

Te veo desde mi ventana

El interés por la fotografía me ha llevado a los objetos y las atmósferas. Estoy atraída por la posibilidad de que en la creación de una imagen lo inerte sea capaz de suscitar sensaciones

Vibrational noise from wind energy-turbines negatively impacts earthworm abundance

Human activities often impact the sensory environment of organisms. Wind energy turbines are a fast-growing potential source of anthropogenic vibrational noise that can affect soil animals sensitive to vibrations and thereby alter soil community functioning. Larger soil animals, such as earthworms (macrofauna, &gt; 1 cm in size), are particularly likely to be impacted by the low-frequency turbine waves that can travel through soils over large distances. Here we examine the effect of wind turbine-induced vibrational noise on the abundance of soil animals. We measured vibrational noise generated by seven different turbines located in organically-farmed crop fields in the Netherlands. Vibratory noise levels dropped by an average of 23 ± 7 dB over a distance of 200 m away from the wind turbines. Earthworm abundance showed a strong decrease with increasing vibratory noise. When comparing the nearest sampling points in proximity of the wind energy turbines with the points furthest away, abundance dropped on average by 40% across all seven fields. The abundance of small-sized soil animals (mesofauna, &lt; 10 mm in size) differed between crop fields, but was not related to local noise levels. Our results suggest that anthropogenic vibratory noise levels can impact larger soil fauna, which has important consequences for soil functioning. Earthworms, for instance, are considered to be crucial ecosystem engineers and an impact on their abundance, survival and reproduction may have knock-on effects on important processes such as water filtration, nutrient cycling and carbon sequestration.</p

Study of the stability and persistence of commercial perfumes under different thermal and UV-Vis light conditions.

Motivation: Nowadays, the perfume industries need to be more and more competitive due to the broad offer existing in the market; For this reason they try to create quality products with optimisted compositions in order to reduce the fabrication costs.In particular, the persistence of the fragrance and stability of the color are the main challanges in the quality of perfumes fabricated by Saphir Laboratories .In this work, we have studied these two propierties in several perfums from this company, stored under diferent agresive conditions of light and temperature. These experiments have been done with different proportions of protective additives in order to optimized the current formulae.Methods: The chemical stability against external factors such as UV light and temperature in terms of the quality and behavior of the samples was study for several perfumes provided by the company (Saphir Laboratories). For these experiencies we have used a UV-Vis lamp( (LOT-Oriel) and a Cary 100 UV-VIs spectrophotometer (Agilent). Additionally, the study of the temperature was carried out by introducing the samples in a lab oven for different periods of time at different temperatures. Different proportions in the perfume composition (Natural essence,water, ethanol,antioxidant BHT,colorants and the UV filters Neosorb and Uvasorb) were used in the above experiments. Finally, the long lasting of the different perfums was analyzed by both human tasting and an electronic nose equipment (SACMI Imola).Results and conclusions: Each perfume has a different behavior,maintaining its identity from 4 to 15 hours exposed to UV depending on the perfum. Regarding the temperature, it can be concluded that at temperatures above 50 ° C the chemical stability of the sample is lost. Additionally, these conditions and even lower temperatures (40ºC) lead to an oxidation of the essential oils, producing rancidity of the essence, which is summarized in more intense olfactory notes with respect to the original perfumes

Influence of light and temperature on the stability of commercial perfumes

Motivation: The industrial sector of perfumes lives many moments of fierce competition among related companies. Survival in this world requires of make technological advances in order to develop products that eliminate unwanted effects, include novelty, and satisfy the customer.The way to achieve this is to do research in order to achieve added value with respect to competitors, such as image, color and design; persistence and anti-aging by oxidation of perfumes due to solar or thermal exposure.In our case, we have perfumes from Saphir Laboratories that present problems with degradation by color, oxidation by redox processes, and low persistence. Whereby, we need to look for optimization ways in order to improve the elaboration recipe at a reduced cost.Methods: Methods used are UV-Vis spectrophotometry using a cary 100 ( Agilent) as colorimeter for colour photodegradation and photoxidation of perfums irradiated with a LOT-Oriel UV-vis lamp. For the persistence studies we compare results of human tastings by non-expert people and measures of intensity by changes in resistance (conductimetric) in a electronic nose powered by an electronic olfactory system software.Results: We have studied four perfumes with color photodegradation problems with promising results. We have found the best proportion of the additives used in their composition . On the other hand, the electronic nose measurements indicate an increase of intensity of odor for samples strored at high temperatures (40ºC) that has been confirmed by human tasting tests . This behaviour has been attributed to a maceration process in pefumes after thermal treatment, simulating our warm climate, given that temperature conditions do not reach 50ºC at which a phase separation takes place.Conclusions: The studies carried out have confirmed that the essential oils of perfumes are the main cause of the loss in the effectiveness of the added UV filters, producing a photodegradation of its own color; we have also achieved favorable results in possible modifications in the proportions of additives to improve the stability. On the other hand, the measures resulting from the electonic nose indicate that thermal treatment of a reconstructed perfume with the addition of ambroxane as fixative reduce the loss of volatile compounds resulting in a greater signal to that of the commercial perfume without ambroxane

Study of SREBP1 and SERBP2 in peripheral blood mononuclear cells fron hypercholesterolemic rabbits

Peripheral blood mononuclear cells are a possible biomarker that could reveal molecular alterations before the development of the disease. Therefore, the objective of the present investigation is to study molecular and genetic changes that indicate metabolic modifications even with normal biochemical values. SERBP1 and SERBP2 are proteins involved in lipid metabolic. These molecules can be expressed in peripheral blood mononuclear cells. This allows study tissue changes without resorting to biopsies. In this study, one control group of New Zealand rabbits was fed with a balanced feed (C) and another group received the same balanced feed supplemented with 17% fat (F). These animals did not receive fructose overload, maintaining constant concentrations of carbohydrates and protein in both groups. In biochemical tests from both groups were observed similar levels of glucose (C group: 140.7 + 28.4 mg/dl / F group: 118.3 +12.0 mg/dl) and triglyceride (C group: 144.1 +15.5 mg/dl / F group: 135.6 +8.3 mg/dl), while F group showed increased levels of cholesterol (42.8 +21.6mg/dl) compared with C group (27.1 +4.5 mg/dl). However, there is variability in the cholesterol values because some animals of the F group do not experience significant increment despite the intake of fat. This interesting finding leads to the hypothesis that changes in lipid metabolism can be examined by the expression of different genes early. As preliminary results, we observed by immunohistochemistry the presence nuclear of SREBP1 and SREBP2 in lymphocytes of the F group, while in C group was not observed immunoreaction or cytoplasmic signal. This result is indicating an activation of the lipid metabolism before being able to observe changes at a biochemical level.Fil: Saez, Aldana. Universidad "Juan Agustín Maza"; ArgentinaFil: Mussi, Jesica. Universidad "Juan Agustín Maza"; ArgentinaFil: Funes, Abi Karenina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Regina Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Fornes, Miguel Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Saez Lancellotti, Tania Emilce Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Boarelli, P. Universidad "Juan Agustín Maza"; ArgentinaXXXVI Reunión Científica Anual de la Sociedad de Biología de CuyoMendozaArgentinaSociedad Argentina de Biologí

Multi-instrumental observations of the 2014 Ursid meteor outburst

The Ursid meteor shower is an annual shower that usually shows little activity. However, its Zenith hourly rate sometimes increases, usually either when its parent comet, 8P/Tuttle, is close to its perihelion or its aphelion. Outbursts when the comet is away from perihelion are not common and outbursts when the comet is close to aphelion are extremely rare. The most likely explanation offered to date is based on the orbital mean motion resonances. The study of the aphelion outburst of 2000 December provided a means of testing that hypothesis. A new aphelion outburst was predicted for 2014 December. The SPanish Meteor Network, in collaboration with the French Fireball Recovery and InterPlanetary Observation Network, set up a campaign to monitor this outburst and eventually retrieve orbital data that expand and confirm previous preliminary results and predictions. Despite unfavourable weather conditions over the south of Europe over the relevant time period, precise trajectories from multistation meteor data recorded over Spain were obtained, as well as orbital and radiant information for four Ursid meteors. The membership of these four meteors to the expected dust trails that were to provoke the outburst is discussed, and we characterize the origin of the outburst in the dust trail produced by the comet in the year AD 1392.Peer reviewe

Quaternary structure of a G-protein coupled receptor heterotetramer in complex with Gi and Gs

Background: G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties of heteromers remain unknown. Results: We used single-particle tracking experiments in cells expressing functional adenosine A1-A2A receptors fused to fluorescent proteins to show the loss of Brownian movement of the A1 receptor in the presence of the A2A receptor, and a preponderance of cell surface 2:2 receptor heteromers (dimer of dimers). Using computer modeling, aided by bioluminescence resonance energy transfer assays to monitor receptor homomerization and heteromerization and G-protein coupling, we predict the interacting interfaces and propose a quaternary structure of the GPCR tetramer in complex with two G proteins. Conclusions: The combination of results points to a molecular architecture formed by a rhombus-shaped heterotetramer, which is bound to two different interacting heterotrimeric G proteins (Gi and Gs). These novel results constitute an important advance in understanding the molecular intricacies involved in GPCR function

Ablation of C-type natriuretic peptide/cGMP signaling in fibroblasts exacerbates adverse cardiac remodeling in mice

Excessive activation of cardiac fibroblasts (CFs) in response to injury provokes cardiac fibrosis, stiffness, and failure. The local mediators counter-regulating this response remain unclear. Exogenous C-type natriuretic peptide (CNP) exerted antifibrotic effects in preclinical models. To unravel the role of the endogenous hormone, we generated mice with fibroblast-restricted deletion (KO) of guanylyl cyclase-B (GC-B), the cGMP-synthesizing CNP receptor.CNP activated GC-B/cGMP signaling in human and murine CFs, preventing proliferative and promigratory effects of AngiotensinII (AngII) and TGF-β. Fibroblast-specific GC-B-KO mice showed enhanced fibrosis in response to AngII infusions. Moreover, after two weeks of mild pressure-overload induced by transverse aortic constriction (TAC), such KO mice had augmented cardiac fibrosis and hypertrophy, together with systolic and diastolic contractile dysfunction. This was associated with increased expression of the profibrotic genes collagen I, III and periostin. Notably, such responses to AngII and TAC were greater in female as compared to male KO mice. Enhanced AngII-induced CNP expression in female hearts and augmented GC-B expression and activity in female CFs may contribute to this sex disparity.The results show that paracrine CNP signaling in CFs has antifibrotic and antihypertrophic effects. The CNP/GC-B/cGMP pathway might be a target for therapies combating pathological cardiac remodeling