The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond

Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor’s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease.     

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.     

Crystallinity variations in kaolinite induced by grinding and pressure treatments

Kaolinite samples treated with uniaxial pressures higher than 0.1 GPa or grinding times greater than 0.3 h show changes in their crystallinity. These changes are easily detected by the X-ray diffraction (XRD) technique and can be quantified from Hinckley (HI), Lietard (R₂) and also reference intensity ratio (RIR) index studies. The sensitivity of these indices to the Crystallinity changes is; HI>RIR>R₂. In the range of pressures and grinding times considered, these values can be diminished by 50%. The variations in these indices with either the pressure or grinding time follow logarithmic laws whose correlation coefficients are closed to unity. Infrared (IR) spectroscopy and thermal analysis studies show low sensitivity to the changes introduced by grinding or pressure. Nevertheless, thermal gravimetric curves confirm the decrease in the dehydroxylation starting point of about 100°C for the pressed and ground samples. Transmission electron microscopy (TEM) reveals important changes in kaolinite particle morphologies after pressure and grinding treatments. The samples compressed at 0.1, 0.32, 0.85, 1.0 and 2.0 GPa show a large number of defects (fractures, bending, deformations and rolling of layers, glide and rotation of the shell). The ground samples show grain boundaries, dislocations, twins and rounded voids. These defects are responsible for the decrease in crystallinity of the kaolinite samples shown in the XRD and IR studies.     

Influence of Manufacturing and Ripening Conditions on the Survival of Enterobacteriaceae in Manchego Cheese

The effects of cooking temperature, time and temperature of brine-salting, and temperature of ripening on the behavior of Enterobacteriaceae in Manchego cheese were studied. Fifty lots of cheese from raw ewe's milk manufactured and ripened under different conditions were investigated throughout a 60-day ripening period. Differences in pH values due to temperature-dependent whey retention accounted for the effect of cooking temperature on coliform and fecal coliform counts. Temperature of brine-salting had no effect on Enterobacteriaceae counts, but a significant effect of salting time on Enterobacteriaceae and fecal coliform counts was detected. Ripening temperature was the manufacturing variable with greatest influence (P<.01) on Enterobacteriaceae and coliform counts during the whole curing period.     

Organic geochemistry of heavy/extra heavy oils from sidewall cores, Lower Lagunillas Member, Tia Juana Field, Maracaibo Basin, Venezuela

The study of 22 oils from sidewall cores taken at different depths in the Lower Lagunillas Member, well LSJ-AB, Tia Juana Field, Maracaibo Lake is presented, with the purpose of predicting the intervals that present the best crude oil quality. Differences were detected in the biodegradation levels of the studied samples, which are correlated with the depth at which the sidewall core was taken. The API gravity was considered for the oils from each sidewall core and it was found that toward the top of the sequence, the oils have an API gravity of 10.6-11.2°, while toward the base part of the sequence, the well produces extra heavy oils with an API gravity that varies between 8.2 and 8.7°.     

Evaluating the influence of multiplexing schemes and buffer implementation on perceived VoIP conversation quality

This work presents a study of RTP multiplexing schemes, which are compared with the normal use of RTP, in terms of experienced quality. Bandwidth saving, latency and packet loss for different options are studied, and some tests of Voice over IP (VoIP) traffic are carried out in order to compare the quality obtained using different implementations of the router buffer. Voice quality is calculated using ITU R-factor, which is a widely accepted quality estimator. The tests show the bandwidth savings of multiplexing, and also the importance of packet size for certain buffers, as latency and packet loss may be affected. The customer’s experience improvement is measured, showing that the use of multiplexing can be interesting in some scenarios, like an enterprise with different offices connected via the Internet. The system is also tested using different numbers of samples per packet, and the distribution of the flows into different tunnels is found to be an important factor in order to achieve an optimal perceived quality for each kind of buffer. Grouping all the flows into a single tunnel will not always be the best solution, as the increase of the number of flows does not improve bandwidth efficiency indefinitely. If the buffer penalizes big packets, it will be better to group the flows into a number of tunnels. The router processing capacity has to be taken into account too, as the limit of packets per second it can manage must not be exceeded. The obtained results show that multiplexing is a good way to improve customer’s experience of VoIP in scenarios where many RTP flows share the same path.     

Adenosine Signaling in Mast Cells and Allergic Diseases

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes.     

Synthesis,characterization, and metal complexation of poly(N‐phenylmaleimide‐co‐acrylic acid) and poly(N‐phenylmaleimide‐co‐acrylamide) as polychelatogens in aqueous solution

We carried out the free‐radical copolymerization of N‐phenylmaleimide with acrylic acid and acrylamide with an equimolar feed monomer ratio. We carried out the synthesis of the copolymers in dioxane at 70°C with benzoyl peroxide as the initiator and a total monomer concentration of 2.5M. The copolymer compositions were obtained by elemental analysis and ¹H‐NMR spectroscopy. The hydrophilic polymers were characterized by elemental analysis, Fourier transform infrared spectroscopy, ¹H‐NMR spectroscopy, and thermal analysis. Additionally, viscosimetric measurements of the copolymers were performed. Hydrophilic poly(N‐phenylmaleimide‐co‐acrylic acid) and poly(N‐phenylmaleimide‐co‐acrylamide) were used for the separation of a series of metal ions in the aqueous phase with the liquid‐phase polymer‐based retention method in the heterogeneous phase. The method is based on the retention of inorganic ions by the polymer in conjunction with membrane filtration and subsequent separation of low‐molecular‐mass species from the formed polymer/metal‐ion complex. The polymer could bind several metal ions, such as Cr(III), Co (II), Zn(II), Ni(II), Cu(II), Cd(II), and Fe(III) inorganic ions, in aqueous solution at pH values of 3, 5, and 7. The interaction of the inorganic ions with the hydrophilic polymer was determined as a function of pH and a filtration factor. Hydrophilic polymeric reagents with strong metal‐complexing properties were synthesized and used to separate those complexed from noncomplexed ions in the heterogeneous phase. The polymers exhibited a high retention capability at pH values of 5 and 7. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006