El final de la guerra civil.

Sin resume

Modulation of mechanosensory vibrissal responses in the trigeminocervical complex by stimulation of the greater occipital nerve in a rat model of trigeminal neuropathic pain.

Background Stimulation of the occipital or trigeminal nerves has been successfully used to treat chronic refractory neurovascular headaches such as migraine or cluster headache, and painful neuropathies. Convergence of trigeminal and occipital sensory afferents in the ‘trigeminocervical complex’ (TCC) from cutaneous, muscular, dural, and visceral sources is a key mechanism for the input-induced central sensitization that may underlie the altered nociception. Both excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) mechanisms are involved in modulating nociception in the spinal and medullary dorsal horn neurons, but the mechanisms by which nerve stimulation effects occur are unclear. This study was aimed at investigating the acute effects of electrical stimulation of the greater occipital nerve (GON) on the responses of neurons in the TCC to the mechanical stimulation of the vibrissal pad. Methods Adult male Wistar rats were used. Neuronal recordings were obtained in laminae II-IV in the TCC in control, sham and infraorbital chronic constriction injury (CCI-IoN) animals. The GON was isolated and electrically stimulated. Responses to the stimulation of vibrissae by brief air pulses were analyzed before and after GON stimulation. In order to understand the role of the neurotransmitters involved, specific receptor blockers of NMDA (AP-5), GABAA (bicuculline, Bic) and Glycine (strychnine, Str) were applied locally. Results GON stimulation produced a facilitation of the response to light facial mechanical stimuli in controls, and an inhibition in CCI-IoN cases. AP-5 reduced responses to GON and vibrissal stimulation and blocked the facilitation of GON on vibrissal responses found in controls. The application of Bic or Str significantly reduced the facilitatory effect of GON stimulation on the response to vibrissal stimulation in controls. However, the opposite effect was found when GABAergic or Glycinergic transmission was prevented in CCI-IoN cases. Conclusions GON stimulation modulates the responses of TCC neurons to light mechanical input from the face in opposite directions in controls and under CCI-IoN. This modulation is mediated by GABAergic and Glycinergic mechanisms. These results will help to elucidate the neural mechanisms underlying the effectiveness of nerve stimulation in controlling painful craniofacial disorders, and may be instrumental in identifying new therapeutic targets for their prevention and treatment.post-print1932 K

Sulfate removal from mine-impacted water by electrocoagulation: statistical study, factorial design, and kinetics

This work aimed to remove sulfate and acidity from mine-impacted water (MIW) via electrocoagulation (EC), a technique which stands as an advanced alternative to chemical coagulation in pollutant removal from wastewaters. The multiple electrochemical reactions occurring in the aluminum anode and the stainless steel cathode surfaces can form unstable flakes of metal hydroxysulfate complexes, causing coagulation, flocculation, and floatation; or, adsorption of sulfate on sorbents originated from the electrochemical process can occur, depending on pH value. Batch experiments in the continuous mode of exposition using different current densities (35, 50, and 65 A m−2) were tested, and a statistical difference between their sulfate removals was detected. Furthermore, the intermittent mode of exposure was also tested by performing a 22-factorial design to verify the combination with different current densities, concluding that better efficiencies of sulfate removal were obtained in the continuous mode of exposition, even with lower current densities. After 5 h of electrocoagulation, sulfate could be removed from MIW with a mean efficiency of 70.95% (in continuous mode of exposition and 65 A m−2 current density), and this sulfate removal follows probable third-order decay kinetics in accordance with the quick drop in sulfate concentration until 3 h of exposure time, remaining virtually constant at longer times

Implication of type 4 NADPH oxidase (NOX4) in tauopathy.

Aggregates of the microtubule-associated protein tau are a common marker of neurodegenerative diseases collectively termed as tauopathies, such as Alzheimer’s disease (AD) and frontotemporal dementia. Therapeutic strategies based on tau have failed in late stage clinical trials, suggesting that tauopathy may be the consequence of upstream causal mechanisms. As increasing levels of reactive oxygen species (ROS) may trigger protein aggregation or modulate protein degradation and, we had previously shown that the ROS producing enzyme NADPH oxidase 4 (NOX4) is a major contributor to cellular autotoxicity, this study was designed to evaluate if NOX4 is implicated in tauopathy. Our results show that NOX4 is upregulated in patients with frontotemporal lobar degeneration and AD patients and, in a humanized mouse model of tauopathy induced by AVV-TauP301L brain delivery. Both, global knockout and neuronal knockdown of the Nox4 gene in mice, diminished the accumulation of pathological tau and positively modified established tauopathy by a mechanism that implicates modulation of the autophagy-lysosomal pathway (ALP) and, consequently, improving the macroautophagy flux. Moreover, neuronal-targeted NOX4 knockdown was sufficient to reduce neurotoxicity and prevent cognitive decline, even after induction of tauopathy, suggesting a direct and causal role for neuronal NOX4 in tauopathy. Thus, NOX4 is a previously unrecognized causative, mechanism-based target in tauopathies and blood-brain barrier permeable specific NOX4 inhibitors could have therapeutic potential even in established disease.post-print5895 K

Catalytic reductive N-alkylation of amines using carboxylic acids

We report a catalytic reductive alkylation reaction of primary or secondary amines with carboxylic acids. The two-phase process involves silane mediated direct amidation followed by catalytic reduction

Role of enzymatic activity inmuscle damage and cytotoxicity induced by Bothrops asper Asp49 phospholipase A2 myotoxins: are there additional effector mechanisms involved?

artículo (arbitrado) -- Universidad de Costa Rica, Instituto de Investigaciones Clodomiro Picado (ICP). 2014Viperid venoms often contain mixtures of Asp49 and Lys49 PLA2 myotoxin isoforms, relevant to development of myonecrosis. Given their difference in catalytic activity, mechanistic studies on each type require highly purified samples. Studies on Asp49 PLA2s have shown that enzyme inactivation using p-bromophenacyl bromide (p-BPB) drastically affects toxicity. However, based on the variable levels of residual toxicity observed in some studies, it has been suggested that effector mechanisms independent of catalysis may additionally be involved in the toxicity of these enzymes, possibly resembling those of the enzymatically inactive Lys49 myotoxins. A possibility that Lys49 isoforms could be present in Asp49 PLA2 preparations exists and, if undetected in previous studies, could explain the variable residual toxicity. This question is here addressed by using an enzyme preparation ascertained to be free of Lys49 myotoxins. In agreement with previous reports, inactivation of the catalytic activity of an Asp49 myotoxin preparation led to major inhibition of toxic effects in vitro and in vivo. The very low residual levels of myotoxicity (7%) and cytotoxicity (4%) observed can be attributed to the low, although detectable, enzyme remaining active after p-BPB treatment (2.7%), and would be difficult to reconcile with the proposed existence of additional catalytic-independent toxic mechanisms. These findings favor the concept that the effector mechanism of toxicity of Asp49 PLA2 myotoxins from viperids fundamentally relies on their ability to hydrolyze phospholipids, arguing against the proposal that membrane disruption may also be caused by additional mechanisms that are independent of catalysis.International Centre for Genetic Engineering and Biotechnology (ICGEB, Italy; CRP/COS13-01); Vicerrectorıa de Investigacion (UCR; 741-B4-100). Sistema de Estudios de Posgrado, Universidad de Costa Rica (SEP-UCR).UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

New reactions under homogeneous conditions

BDTBPMB has been proven to be an essential ligand in carbonylation chemistry. Its two tert-butyl groups and wide bite angle give it the ideal characteristics for this kind of chemistry, and leads to high activity and selectivity with use of its complexes. During this work the group of reactions where this ligand has been proven to be active has been extended with two new protocols for hydroxycarbonylation and aminocarbonylation. In the hydroxycarbonylation process, a large variety of unsaturated compounds were studied. Dioxane was found to be the ideal solvent, due to its properties in terms of coordinability, and miscibility with water. Using this solvent as the medium, a BDTBPMB complex of palladium was found to be highly active and selective under mild conditions. Initial attempts to address the aminocarbonylation of alkenes catalysed by the Pd/BDTBPMB system did not give high activity. This problem was overcome by the addition of an arylalcohol. Under those conditions, high selectivity and conversion was obtained in a wide variety of amides. However, attempts to address the aminocarbonylation of alkenes with ammonia gas to generate primary amides did not result in any conversion. The generation of these primary amides was obtained with transamidation of N-phenylnonamides which can be prepared by aminocarbonylation. Amides have been successfully hydrogenated to amines catalysed by a Ru/Triphos system. This system has been proven to be highly active in this reaction. High selectivities have been obtained in the generation of secondary amine. However, initial results of the hydrogenation of primary amides resulted in no formation of primary amines. A careful analysis of the mechanism of the formation of various products from the hydrogenation of primary amides allows the selective formation of primary amines by the ruthenium/Triphos system in the presence of ammonia. The possibility of the generation of primary amides in situ from acids under hydrogenation conditions, giving primary amines was explored with high conversion and moderate selectivities.To complete this work, a system based on a palladium complex for the decarboxylation of benzoic acids was developed. Usually, the decarboxylation reactions catalysed by copper require high temperatures. However, palladium complexes of highly electron donating ligands such as BDTBPMB or P(ᵗBu)₃ were found to be highly active under milder conditions. This catalytic system was proven to be active in desulfonation reactions giving high conversion