Variable threshold of trigeminal cold-thermosensitive neurons is determined by a balance between TRPM8 and Kv1 potassium channels

Molecular determinants of threshold differences among cold thermoreceptors are unknown. Here we show that such differences correlate with the relative expression of IKD, a current dependent on Shaker-like Kv1 channels that acts as an excitability brake, and ITRPM8, a cold-activated excitatory current. Neurons responding to small temperature changes have high functional expression of TRPM8 (transient receptor potential cation channel, subfamily M, member 8) and low expression of IKD. In contrast, neurons activated by lower temperatures have a lower expression of TRPM8 and a prominent IKD. Otherwise, both subpopulations have nearly identical membrane and firing properties, suggesting that they belong to the same neuronal pool. Blockade of IKD shins the threshold of cold-sensitive neurons to higher temperatures and augments cold-evoked nocifensive responses in mice. Similar behavioral effects of IKD blockade were observed in TRPA1-/- mice. Moreover, only a small percentage of trigeminal cold-sensitive neurons were activated by TRPA1 agonists, suggesting that TRPA1 does not play a major role in the detection of low temperatures by uninjured somatic cold-specific thermosensory neurons under physiological conditions. Collectively, these findings suggest that innocuous cooling sensations and cold discomfort are signaled by specific low- and high-threshold cold thermoreceptor neurons, differing primarily in their relative expression of two ion channels having antagonistic effects on neuronal excitability. Thus, although TRPM8 appears to function as a critical cold sensor in the majority of peripheral sensory neurons, the expression of Kv1 channels in the same terminals seem to play an important role in the peripheral gating of cold-evoked discomfort and pain. Copyright © 2009 Society for Neuroscience.This work was supported by funds from the Spanish Ministry of Education and Science: Projects BFU2007-61855 to F.V., and BFU2005-08741 and CONSOLIDER-INGENIO 2010 CSD2007-00023 to C.B., and the Spanish Fundación Marcelino BotínPeer Reviewe

Performance Testing of a Large-Format Reflection Grating Prototype for a Suborbital Rocket Payload

The soft X-ray grating spectrometer on board the Off-plane Grating Rocket Experiment (OGRE) hopes to achieve the highest resolution soft X-ray spectrum of an astrophysical object when it is launched via suborbital rocket. Paramount to the success of the spectrometer are the performance of the $>250$ reflection gratings populating its reflection grating assembly. To test current grating fabrication capabilities, a grating prototype for the payload was fabricated via electron-beam lithography at The Pennsylvania State University's Materials Research Institute and was subsequently tested for performance at Max Planck Institute for Extraterrestrial Physics' PANTER X-ray Test Facility. Bayesian modeling of the resulting data via Markov chain Monte Carlo (MCMC) sampling indicated that the grating achieved the OGRE single-grating resolution requirement of $R_{g}(\lambda/\Delta\lambda)>4500$ at the 94% confidence level. The resulting $R_g$ posterior probability distribution suggests that this confidence level is likely a conservative estimate though, since only a finite $R_g$ parameter space was sampled and the model could not constrain the upper bound of $R_g$ to less than infinity. Raytrace simulations of the system found that the observed data can be reproduced with a grating performing at $R_g=\infty$. It is therefore postulated that the behavior of the obtained $R_g$ posterior probability distribution can be explained by a finite measurement limit of the system and not a finite limit on $R_g$. Implications of these results and improvements to the test setup are discussed.Comment: 25 pages, 16 figures, preprint of an article accepted for publication in the Journal of Astronomical Instrumentation \copyright 2020 [copyright World Scientific Publishing Company] [https://www.worldscientific.com/worldscinet/jai

Genetic association of CDC2 with cerebrospinal fluid tau in Alzheimer's disease

We have recently reported that a polymorphism in the cell division cycle (CDC2) gene, designated Ex6 + 7I/D, is associated with Alzheimer's disease (AD). The CDC2 gene is located on chromosome 10q21.1 close to the marker D10S1225 linked to AD. Active cdc2 accumulates in neurons containing neurofibrillary tangles (NFT), a process that can precede the formation of NFT. Therefore, CDC2 is a promising candidate susceptibility gene for AD. We investigated the possible effects of the CDC2 polymorphism on cerebrospinal fluid (CSF) biomarkers in AD patients. CDC2 genotypes were evaluated in relation to CSF protein levels of total tau, phospho-tau and beta-amyloid (1-42) in AD patients and control individuals, and in relation to the amount of senile plaques and NFT in the frontal cortex and in the hippocampus in patients with autopsy-proven AD and controls. The CDC2 Ex6 + 7I allele was associated with a gene dose-dependent increase of CSF total tau levels (F-2,F- 626 = 7.0, p = 0.001) and the homozygous CDC2Ex6 +7II genotype was significantly more frequent among AD patients compared to controls (p = 0.006, OR = 1.57, 95% CI 1.13-2.17). Our results provide further evidence for an involvement of cdc2 in the pathogenesis of AD. Copyright (C) 2005 S. Karger AG, Basel

Advances in prevention and therapy of neonatal dairy calf diarrhoea : a systematical review with emphasis on colostrum management and fluid therapy

Neonatal calf diarrhoea remains the most common cause of morbidity and mortality in preweaned dairy calves worldwide. This complex disease can be triggered by both infectious and non-infectious causes. The four most important enteropathogens leading to neonatal dairy calf diarrhoea are Escherichia coli, rota-and coronavirus, and Cryptosporidium parvum. Besides treating diarrhoeic neonatal dairy calves, the veterinarian is the most obvious person to advise the dairy farmer on prevention and treatment of this disease. This review deals with prevention and treatment of neonatal dairy calf diarrhoea focusing on the importance of a good colostrum management and a correct fluid therapy

A Characterization of Scale Invariant Responses in Enzymatic Networks

An ubiquitous property of biological sensory systems is adaptation: a step increase in stimulus triggers an initial change in a biochemical or physiological response, followed by a more gradual relaxation toward a basal, pre-stimulus level. Adaptation helps maintain essential variables within acceptable bounds and allows organisms to readjust themselves to an optimum and non-saturating sensitivity range when faced with a prolonged change in their environment. Recently, it was shown theoretically and experimentally that many adapting systems, both at the organism and single-cell level, enjoy a remarkable additional feature: scale invariance, meaning that the initial, transient behavior remains (approximately) the same even when the background signal level is scaled. In this work, we set out to investigate under what conditions a broadly used model of biochemical enzymatic networks will exhibit scale-invariant behavior. An exhaustive computational study led us to discover a new property of surprising simplicity and generality, uniform linearizations with fast output (ULFO), whose validity we show is both necessary and sufficient for scale invariance of enzymatic networks. Based on this study, we go on to develop a mathematical explanation of how ULFO results in scale invariance. Our work provides a surprisingly consistent, simple, and general framework for understanding this phenomenon, and results in concrete experimental predictions

Primer registro de Sargocentron coruscum (Holocentridae) en el suroeste del golfo de México

El presente estudio reporta por primera vez la presencia del pez ardilla Sargocentron coruscum para el suroeste del golfo de México. El avistamiento se realizó en el arrecife Lobos durante un muestreo nocturno en la pendiente de sotavento a 3 m de profundidad. Se observó un individuo de aproximadamente 15 cm entre oquedades de rocas coralinas. Este registro amplía el ámbito de distribución de S. coruscum para el suroeste del golfo de México e incrementa el conocimiento de la riqueza ictiológica de la región, la cual continua en ascenso con nuevos hallazgos en los últimos años

LA HISTIDINA COMO UN POSIBLE PRECURSOR EN EL ORIGEN DE LA VIDA

Los procesos químicos que se dieron durante los primeros años de la evolución del planeta Tierra, -antes de la presencia de formas celulares-, han sido motivo continuo de estudios a nivel experimental en muchos laboratorios. Considerando ambientes prebióticos plausibles, se ha dado importancia y validez a la presencia de materiales, tales como minerales y arcillas, que pudieron aportar elementos químicos necesarios para catalizar reacciones químicas y estabilizar otro tipo de compuestos orgánicos. La estructura cristalina de algunas biomoléculas de importancia biológica, así como su estereoquímica pueden llevarnos a comprender algunas de las formas de compuestos descritos en el espacio; en particular los compuestos orgánicos mencionados en algunas meteoritas. Finalmente, aportar elementos que nos ayuden a dar nuevas evidencias sobre el ¿cómo? y el ¿por qué? de la existencia de algunas moléculas de importancia biológica, siempre enriquecen el campo científico, y en particular abren nuevos horizontes para entender la relevancia en los procesos fisicoquímicos y más tardíamente, los procesos metabólicos, que pudieron dar lugar a organismos vivos de tipo unicelular en la Tierra primitiva. En el presente trabajo se discute la importancia de la histidina como catalizador orgánico en los estudios sobre el origen de la vida. Se presentan los resultados preliminares sobre la formación de monocristales de histidina en una disolución acuosa y sus posibles implicaciones como aminoácido esencial para la formación de oligopéptidos. Además se plantea la posibilidad de que este aminoácido haya actuado en un momento dado, como catalizador de ciertas reacciones químicas vitales en muchos seres vivos, apoyando su potencial actividad como catalizador orgánico.//The chemical processes occurred during the first years of the evolution of the planet Earth, before the presence of cellular forms, have been continuous reason of studies at experimental level in many laboratories. Considering some possible prebiotic environments, the presence of materials such as clays-type minerals, which could provide chemical and structural elements such as their surfaces, have been given importance and validity to give protection and reactivity to the organic molecules existing in the surrounding environment. These catalytic processes, mediated by mineral surfaces, could give rise in the interstellar medium to a whole range of organic molecules. Many of these are low molecular weights, such as amino acids and carboxylic acids and sometimes molecular weights are much higher. Providing elements that help us to give new evidence about the origin of some molecules of biological importance in the interstellar medium, always enrich the scientific field related to the origin of life, and in particular open new horizons to understand the relevance of physicochemical processes that Could give rise to living organisms on primitive Earth. The present work discusses the possible abiotic synthesis of the amino acid histidine and its importance as an organic catalyst in the formation of oligopeptides in simulations of reactions at the origin of life. In this paper, we discuss the relevance of having histidine monocrystals, simulating a process of hydration-dehydration in shallow pools on the primitive Earth; A phenomenon that is essential for the formation of oligopeptides and, in turn, generate supramolecular assemblies before the appearance of life on our planet