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ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family is known to play an important role in the pathogenesis of osteoarthritis ( OA), working on aggrecan degradation or altering the integrity of extracellular matrix ( ECM). Thus, the main purpose of our study was to define the role of vasoactive intestinal peptide ( VIP) and corticotrophin-releasing factor ( CRF), as immunoregulatory neuropeptides, on ADAMTS production in synovial fibroblasts ( SF) from OA patients and healthy donors ( HD). OA- and HD- SF were stimulated with pro-inflammatory mediators and treated with VIP or CRF. Both neuropeptides decreased ADAMTS-4, -5, -7 and -12 expressions, aggrecanase activity, glycosaminoglycans ( GAG), and cartilage oligomeric matrix protein ( COMP) degradation after stimulation with fibronectin fragments (Fn-fs) in OA- SF. After stimulation with interleukin-1β, VIP reduced ADAMTS-4 and -5, and both neuropeptides decreased ADAMTS-7 production and COMP degradation. Moreover, VIP and CRF reduced Runx2 and β-catenin activation in OA- SF. Our data suggest that the role of VIP and CRF on ADAMTS expression and cartilage degradation could be related to the OA pathology since scarce effects were produced in HD- SF. In addition, their effects might be greater when a degradation loop has been established, given that they were higher after stimulation with Fn-fs. Our results point to novel OA therapies based on the use of neuropeptides, since VIP and CRF are able to stop the first critical step, the loss of cartilage aggrecan and the ECM destabilization during joint degradation. [ABSTRACT FROM AUTHOR]

Multisensory convergence of visual and vestibular signals has been observed within a network of cortical areas involved in representing heading. Vestibular-dominant heading tuning has been found in the macaque parietoinsular vestibular cortex (PIVC) and the adjacent visual posterior sylvian (VPS) area, whereas relatively balanced visual/vestibular tuning was encountered in the ventral intraparietal (VIP) area and visual-dominant tuning was found in the dorsal medial superior temporal (MSTd) area. Although the respective functional roles of these areas remain unclear, perceptual deficits in heading discrimination following reversible chemical inactivation of area MSTd area suggested that areas with vestibular-dominant heading tuning also contribute to behavior. To explore the roles of other areas in heading perception, muscimol injections were used to reversibly inactivate either the PIVC or the VIP area bilaterally in macaques. Inactivation of the anterior PIVC increased psychophysical thresholds when heading judgments were based on either optic flow or vestibular cues, although effects were stronger for vestibular stimuli. All behavioral deficits recovered within 36 h. Visual deficits were larger following inactivation of the posterior portion of the PIVC, likely because these injections encroached upon the VPS area, which contains neurons with optic flow tuning (unlike the PIVC). In contrast, VIP inactivation led to no behavioral deficits, despite the fact that VIP neurons show much stronger choice-related activity than MSTd neurons. These results suggest that the VIP area either provides a parallel and partially redundant pathway for this task, or does not participate in heading discrimination. In contrast, the PIVC/VPS area, along with the MSTd area, make causal contributions to heading perception based on either vestibular or visual signals. [ABSTRACT FROM AUTHOR]

Inhibitory interneurons in the neocortex often connect in a promiscuous and extensive fashion, extending a "blanket of inhibition" on the circuit. This raises the problem of how can excitatory activity propagate in the midst of this widespread inhibition. One solution to this problem could be the vasoactive intestinal peptide (VIP) interneurons, which disinhibit other interneurons. To explore how VIP interneurons affect the local circuits, we use two-photon optogenetics to activate them individually in mouse visual cortex in vivo while measuring their output with two-photon calcium imaging. We find that VIP interneurons have narrow axons and inhibit nearby somatostatin interneurons, which themselves inhibit pyramidal cells. Moreover, via this lateral disinhibition, VIP cells in vivo make local and transient "holes" in the inhibitory blanket extended by SOM cells. VIP interneurons, themselves regulated by neuromodulators, may therefore enable selective patterns of activity to propagate through the cortex, by generating a "spotlight of attention". [ABSTRACT FROM AUTHOR]

In Swedish district heating networks, around 10% of the supplied thermal energy is lost in the distribution system. One solution to decrease the losses is to use hybrid insulation district heating pipes, a concept where the innermost part of the thermal insulation consists of vacuum insulation panels, held in place by polyurethane foam. One problem with vacuum insulation panels are their sensitivity to high temperatures. This paper presents field measurements on a hybrid insulation district heating pipe where the temperatures have been measured continuously at various positions of a pipe section. The measurements show consistency and a large difference between hybrid insulation parts and reference parts without vacuum insulation panels. A superposition model has been used to calculate the temperature in a point and compare it to the measurement. The results are compared to the same calculation on the results from finite element simulations. The results show clearly that the vacuum panels in the pipes have not collapsed. A slow deterioration of the panels is harder to find with this model. Changes in the system, such as a return temperature which decreases over time, can give a larger impact, concealing the change in the panel performance. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor (Fgf) 8 is essential for the development of multiple brain regions. Previous studies from our laboratory showed that reduced Fgf8 signaling led to the developmental alterations of neuroendocrine nuclei that originated within the diencephalon, including the paraventricular (PVN) and supraoptic (SON) nuclei. To further understand the role of Fgf8 in the development of other hypothalamic nuclei, we examined if Fgf8 and its cognate receptor, Fgfr1, also impact the integrity of the suprachiasmatic nuclei (SCN). The SCN control an organism's circadian rhythm and contain vasoactive intestinal peptide (VIP)-producing neurons as the main input neurons. Mice hypomorphic for Fgf8, Fgfr1, or both were examined for their SCN volume and the number of VIP neurons on postnatal day (PN) 0; adult hypomorphic mice were further examined for SCN function by quantifying SCN neuronal activation using cFos as a marker. On PN0, mice homozygous for Fgf8 hypomorphy displayed the most severe reduction of the SCN volume and VIP neurons. Those heterozygous for Fgf8 hypomorphy alone or Fgf8 combined with Fgfr1 hypomorphy, called double heterozygotes (DH), showed normal SCN volume but significantly reduced VIP neurons, albeit less severely than the homozygotes. Adult wild type, heterozygous Fgf8 hypomorphs (F8 Het), and DH mice were also examined for SCN cFos activation at three time points: 1 h (morning), 6 h (afternoon), and 11 h (evening) after light onset. In F8 Het mice, a significant change in the pattern of cFos immunostaining that may reflect delayed morning SCN activation was observed. Overall, our studies provide evidence supporting that deficiencies in Fgf8 not only impact the structural integrity of the SCN but also the pattern of SCN activation in response to light. [ABSTRACT FROM AUTHOR]

The care of Very Important Patients (VIPs) is different from other patients because they may receive greater access, attention, and resources from health care staff. Although the term VIP is used regularly in the medical literature and is implicitly understood, in practice it constitutes a wide and heterogeneous group of patients that have a strong effect on health care providers. We define a VIP as a very influential patient whose individual attributes and characteristics (eg, social status, occupation, position), coupled with their behavior, have the potential to significantly influence a clinician's judgment or behavior. Physicians, celebrities, the politically powerful, and philanthropists, may all become VIPs in the appropriate context. The quality of care may be inferior because health care professionals may deviate from standard practices when caring for them. Understanding the common features among what may otherwise be very different groups of patients can help health care providers manage ethical concerns when they arise. We use a series of vignettes to demonstrate how VIPs behavior and status can influence a clinician's judgment or actions. Appreciating the ethical principles in these varied circumstances provides health care professionals with the tools to manage ethical conflicts that arise in the care of VIPs. We conclude each vignette with guidance for how health care providers and administrators can manage the ethical concern. [ABSTRACT FROM AUTHOR]

Vacuum Insulation Panels (VIPs) are characterised by very low thermal conductivity, compared to traditional insulating materials. For this reason, they represent a promising solution to improve the thermal behaviour of buildings, especially in the case of energy retrofitting (where a higher performance and less thickness is desirable). VIPs are insulating components in which a core material is surrounded by an air tight envelope which allows a high degree of internal vacuum to be maintained. Such features, on the one hand, allow excellent thermal insulation properties to be achieved, but, on the other, require the manufacturing of prefabricated panels of fixed shape/size. This means that the use of these super insulating materials in the building envelope involves the problem of joining the panels to each other and of fixing them onto additional supporting elements. As a result, purposely studied supporting structures or systems are required. However, these structures and systems cause thermal bridging effects. The overall energy performance of the resulting insulation package can therefore be affected to a great extent by these additional elements, and can become significantly lower than that of the VIP panel alone. In order to verify the incidence of thermal bridges on the overall energy performance of an insulation system that makes use of VIP panels, an experimental campaign has been carried out using a heat flux metre apparatus and analysing different joint materials/typologies. First, a measurement method was proposed, tested and verified on the basis of data from the available literature. A series of measurements on different samples was then performed. The experimental results were then used to calibrate and verify a numerical model that allows the performance of various “VIP packages” to be predicted and the performance of the overall package to be optimised. [ABSTRACT FROM AUTHOR]

It is now recognized that G protein-coupled receptors (GPCRs), once considered largely independent functional units, have a far more diverse molecular architecture. Receptor activity-modifying proteins (RAMPs) provide an important example of proteins that interact with GPCRs to modify their function. RAMPs are able to act as pharmacological switches and chaperones, and they can regulate signaling and/or trafficking in a receptor-dependent manner. This review covers recent discoveries in the RAMP field and summarizes the known GPCR partners and functions of RAMPs. We also discuss the first peptide-bound structures of RAMP-GPCR complexes, which give insight into the molecular mechanisms that enable RAMPs to alter the pharmacology and signaling of GPCRs. [ABSTRACT FROM AUTHOR]

Costa Rican natural ecosystems are among the most diverse in the world. For this reason, we isolated strains of the entomopathogenic bacteria Bacillus thuringiensis (Bt ) to determine their diversity, distribution and abundance. A total of 146 Bt strains were obtained from environmental samples collected from diverse natural ecosystems and life zones of Costa Rica. We recovered Bt strains from 71%, 63%, 61% and 54% of soil samples, fresh leaves, other substrates and leaf litter respectively. Bt was isolated in 65%of the samples collected in the humid tropical forest in national parks (Braulio Carrillo, Gandoca Manzanillo, Sierpe, Hitoy Cerere, and Cahuita), and in 59% of the samples collected in the dry tropical forest (Parque Nacional Marino las Baulas, Palo Verde and Santa Rosa). In the very humid tropical forest (Tortuguero) Bt was isolated in 75% of the samples and in the very humid tropical forest transition perhumid (Carara)it was found in 69% of the samples. The strains exhibit a diverse number, size and morphology of parasporal inclusion bodies: irregular (47%),oval (20%), bipyramidal (3%), bipyramidal and cubic (1%), bipyramidal, oval and irregular (5%) and bipyramidal, oval and cubic crystals (2%). Strains isolated from Braulio Carrillo, Tortuguero and Cahuita, presented predominantly irregular crystals. On the other hand, more than 60% of the isolates from Térraba-Sierpe and Hitoy-Cerere had medium oval crystals. Strains from Gandoca-Manzanillo, Palo Verde and Carara presented mainly combinations of oval and irregular crystals. Nevertheless, the greatest diversity in crystal morphology was observed in those from Santa Rosa, Llanos del Río Medio Queso and Parque Marino las Baulas. Protein analyses of the crystal-spore preparations showed ä -endotoxin with diverse electrophoretic patterns, with molecular weights in the range of 20 to 160 kDa. Fifty six percent of the strains amplified with the cry2 primer, 54% with vip3, 20% with cry1, 9% with cry3-cry7 and 8% with cry8. The cry 11 and cyt genes were found in 8% and 7% of the strains, respectively. When analyzed with specific primers for the cry1 subfamily, 13 different genetic profiles were obtained. In addition, twenty-four strains did not amplify with any of the primers used, suggesting they contain novel cry genes. The diversity of Bt genes found in this collection indicates it could have great potential for the control of different species of insect pests. The toxicological characterization of the strains by bioassays against important insect pests will provide useful information about their potential use for the formulation of biological insecticides and their respective cry and vip genes for the transformation of crops to confer resistance to insects. Rev. Biol. Trop. 54(1):13-27.Epub 2006 Mar 31.Como los ecosistemas naturales de Costa Rica figuran entre los más diversos del mundo, se propuso aislar la bacteria entomopatógena Bacillus thuringiensis (Bt ) con el fin de conformar una colección de cepas y caracterizarlas molecularmente. Se obtuvieron 146 cepas a partir de muestras ambientales de diversas áreas protegidas, que incluían 9 de las 12 zonas de vida de Costa Rica. Se recobraron cepas del 71%, 63%, 61%y 54% de las muestras de suelo, hojas frescas, otros sustratos y hojarasca respectivamente. Se aisló Bt del 65% de las muestras del bosque tropical húmedo, un 59% de las muestras del bosque tropical seco. Del bosque tropical muy húmedo se aisló Bt del 75% de las muestras y finalmente del bosque tropical muy húmedo transición perhúmedo se encontró en el 69% de las muestras. Las cepas se caracterizaron según la morfología de los cuerpos paraesporales de inclusión, el peso molecular de las ä -endotoxinas y de genes cry,cyt y vip que contenían. Las cepas exhibieron cristales de diferente morfología, tamaño y número: irregulares, ovales, bipiramidales, cúbicos o mezclas de uno u otro. No se encontró correlación al comparar la forma de los cristales con el sitio de origen de la cepa. El análisis proteico de las mezclas de esporas y cristales mostró que las cepas contenían ä -endotoxinas de 20 a 160 kDa.El 66 por ciento de las cepas amplificaron con los imprimadores específicos para el gen cry2,54% con vip3, 20% con el cry1, 9% con el cry3-cry7 y 8% con el gen cry8. Los genes cry11 y cyt se encontraron en el 8%y 7% de las cepas respectivamente. Veinticuato cepas no amplificaron con los imprimadores utilizados por lo que podrían contener genes novedosos. Las cepas que contenían el gen cry1 se amplificaron posteriormente con imprimadores específicos para la subfamilia de dicho gen, obteniéndose 13 perfiles diferentes. En síntesis, la diversidad genética de las cepas sugiere que la colección tiene un gran potencial para el control de diferentes especies de insectos de importancia económica en la agricultura y en salud pública. El análisis toxicológico de las cepas mediante bioensayos con insectos plaga proveerá información muy útil acerca del uso potencial de estas cepas para la formulación de bioinsecticida. Asimismo, lo genes cry y vip podrían utilizarse para, mediante ingeniería genética, conferir resistencia a los cultivos.

Vasoactive intestinal peptide (VIP) mediates a broad range of biological responses by activating two related receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2). Although the use of native VIP facilitates neuroprotection, clinical application of the hormone is limited due to VIP's rapid metabolism and inability to distinguish between VIPR1 and VIPR2 receptors. In addition, activation of both receptors by therapeutics may increase adverse secondary toxicities. Therefore, we developed metabolically stable and receptor-selective agonists for VIPR1 and VIPR2 to improve pharmacokinetic and pharmacodynamic therapeutic end points. Selective agonists were investigated for their abilities to protect mice against MPTP-induced neurodegeneration used to model Parkinson's disease (PD). Survival of tyrosine hydroxylase neurons in the substantia nigra was determined by stereological tests after MPTP intoxication in mice pretreated with either VIPR1 or VIPR2 agonist or after adoptive transfer of splenic cell populations from agonist-treated mice administered to MPTP-intoxicated animals. Treatment with VIPR2 agonist or splenocytes from agonist-treated mice resulted in increased neuronal sparing. Immunohistochemical tests showed that agonist-treated mice displayed reductions in microglial responses, with the most pronounced effects in VIPR2 agonist-treated, MPTP-intoxicated mice. In parallel studies, we observed reductions in proinflammatory cytokine release that included IL-17A, IL-6, and IFN-α and increases in GM-CSF transcripts in CD4+ T cells recovered from VIPR2 agonist-treated animals. Moreover, a phenotypic shift of effector to regulatory T cells was observed. These results support the use of VIPR2-selective agonists as neuroprotective agents for PD treatment. [ABSTRACT FROM AUTHOR]

The capital concept has proliferated in studies of culture and stratification, usually depicting individual assets as personal advantages within given fields. Because this approach sidesteps issues of ownership, it obscures how unequal value can be generated through the appropriation of someone else's capital. Based on fieldwork in the global VIP party circuit from New York to Cannes, as well as 84 interviews with party organizers and patrons, I document the uses of women's bodily capital by men who appropriate women as a symbolic resource to generate profit, status, and social ties in an exclusive world of businessmen. I argue that women are unable to capitalize on their bodily capital as effectively through participation in the VIP scene because codes of sexual morality penalize women for strategic intimacy. By shifting the analysis of capital from individual advantages to systemic extra-individual advantages, this article brings appropriation into the study of culture and class. Further, this article genders the elite by documenting the cultural incompatibilities of femininity in elite men's social spaces. [ABSTRACT FROM AUTHOR]

Various tumor cells express significantly higher amounts of VIP receptors (VIPR) that provided the basis for the clinical use of radiolabeled VIP for the in vivo localization of tumors. This work studied the labeling of VIP and VIP10-28 with iodine-131 to compare the biological distribution of the labeled compounds in Nuce mice and the affinity for tumor cells. Both VIP and VIP10-28 peptides contain two tyrosine residues, in positions 10 and 22, that are theoretically equally susceptible to radioiodination employing oxidative electrophilic substitution using oxidizing agents like Chloramine T. Radiochemical purity of the reaction mixture was determined by electrophoresis and HPLC. The VIP peptide and the fragment were labeled with radioiodine with good radiochemical yield (above 96%). Suitable, but important differences can be observed in biological distribution studies. Comparatively, blood clearance was faster for labeled VIP and perhaps because of this, the uptake in tumor was lower, especially during the first hour. These differences observed in the biological distribution of the compounds can be related to the lipophilicity of the labeled compounds.Várias células tumorais expressam significantemente uma alta quantidade de receptores VIP (VIPR) que determinam a base para o uso clínico de VIP radiomarcado para localização de tumores in vivo. Foi estudado neste trabalho a marcação do VIP e do fragmento VIP10-28 com iodo-131 comparando a distribuição biológica dos compostos marcados em camundongos Nude e sua afinidade pelas células tumorais. Ambos os peptídeos, VIP e VIP10-28. contém dois resíduos de tirosina nas posições 10 e 22, que teoricamente são igualmente susceptíveis pela substituição eletrofílica oxidativa do radioiodo utilizando Cloramina T como agente oxidante. A pureza radioquímica da mistura de reação foi determinada por eletroforese e cromatografia líquida de alta eficiência (CLAE). O VIP e fragmento foram marcados com radioiodo com bom rendimento radioquímico (superior a 96%). Importantes diferenças foram observadas nos estudos de distribuição biológica. Comparativamente, o clareamento sanguíneo foi mais rápido para VIP marcado e por esta razão, a captação no tumor foi inferior, especialmente na primeira hora. Estas diferenças observadas na distribuição biológica dos compostos podem estar relacionadas com a lipofilicidade dos compostos marcados.

The effect of the treatment with acetyl-L-carnitine (ALC) on neurons releasing the vasoactive intestinal polypeptide (VIP) of the submucous plexus in the jejunum of diabetic rats was the purpose of our investigation. Diabetes (DM) was induced by injecting streptozotocin endovenously (35mg/kg). After sacrificing the animals, the jejunum was collected and processed for VIP detection. Four groups were used: C (non-diabetic), CC (non-diabetic treated with ALC), D (diabetic), DC (diabetes treated with ALC). We analyzed the immunoreactivity and the cellular profile of 126 cell bodies. The treatment with ALC improved some aspects of DM. However, it promoted a small increase in the area of neurons from group CC, suggesting a possible neurotrophic effect. Neurons from groups D and DC showed a large increase in their cellular profile and immunoreactivity when compared to C and CC, suggesting a larger concentration of this neurotransmitter within the neurons that produce it. This observation constitutes a recurrent finding in diabetic animals, suggesting that ALC doesnot interfere in the pathophysiological mechanisms that unchain a higher production and/or neurotransmitter accumulation and increase the profile of the VIP-ergic neurons.

VIP binding sites are upregulated in mesial temporal lobe epilepsy (MTLE) patients, also suffering from severe cognitive deficits. Although altered VIP and VIP receptor levels were described in rodent models of epilepsy, the VIP receptor subtype(s) were never identified. We now investigated how VPAC 1 and VPAC 2 receptor levels change in the Li2+-pilocarpine rat model of MTLE. Cognitive decline and altered synaptic plasticity as estimated from phosphorylation of AMPA GluA1 subunit on Ser831 and Ser845 and AMPA GluA1/GluA2 ratio was also probed. Animals showing spontaneous recurrent seizures (SRSs) for at least 4 weeks showed impaired learning in the radial arm maze (RAM) and presented decreased VPAC 1 and increased VPAC 2 receptor levels. In addition, SRSs rats showed increased AMPA GluA1 phosphorylation in Ser831 and Ser845, marked decrease in GluA1 levels and a milder decrease in GluA2 levels. Consequently, the GluA1/GluA2 ratio was also decreased in SRSs rats. Altered VIP receptor levels may differentially prevent or contribute to MTLE pathology, since VPAC 1 receptors promote the endogenous control of LTP, mediate endogenous VIP neuroprotection against altered synaptic plasticity following epileptiform activity, and mediate anti-inflammatory actions in microglia, while VPAC 2 receptors mediate VIP endogenous neuroprotection against neonatal excitotoxicity and prevent reactive astrogliosis. This discovery imposes a different mindset for considering VIP receptors as therapeutic targets in MTLE, allowing a differential targeting of the cellular events contributing to epileptogenesis. • Hippocampal VIP VPAC 1 receptors are downregulated and VPAC 2 receptors upregulated in the Li2+-pilocarpine model of MTLE. • Spatial memory impairment and altered AMPA R structure and GluA1 phosphorylation preclude altered synaptic plasticity. • Diminished VPAC 1 receptors may contribute to LTP saturation and inflammation in MTLE. • Enhanced VPAC 2 receptors may lessen excitotoxicity, increase neuronal survival, and prevent reactive astrogliosis in MTLE. [ABSTRACT FROM AUTHOR]

A genetic basis for the anatomic master circadian clock in mammals has been found.

The robustness and limited plasticity of the master circadian clock in the suprachiasmatic nucleus (SCN) is attributed to strong intercellular communication among its constituent neurons. However, factors that specify this characteristic feature of the SCN are unknown. Here, we identified Lhx1 as a regulator of SCN coupling. A phase-shifting light pulse causes acute reduction in Lhx1 expression and of its target genes that participate in SCN coupling. Mice lacking Lhx1 in the SCN have intact circadian oscillators, but reduced levels of coupling factors. Consequently, the mice rapidly phase shift under a jet lag paradigm and their behavior rhythms gradually deteriorate under constant condition. Ex vivo recordings of the SCN from these mice showed rapid desynchronization of unit oscillators. Therefore, by regulating expression of genes mediating intercellular communication, Lhx1 imparts synchrony among SCN neurons and ensures consolidated rhythms of activity and rest that is resistant to photic noise.

We examined some of the mechanisms by which the aspirin metabolite and the naturally occurring metabolite gentisic acid induced relaxation of the guinea pig trachea in vitro. In preparations with or without epithelium and contracted by histamine, gentisic acid caused concentration-dependent and reproducible relaxation, with mean EC50 values of 18 µM and Emax of 100% (N = 10) or 20 µM and Emax of 92% (N = 10), respectively. The relaxation caused by gentisic acid was of slow onset in comparison to that caused by norepinephrine, theophylline or vasoactive intestinal peptide (VIP). The relative rank order of potency was: salbutamol 7.9 > VIP 7.0 > gentisic acid 4.7 > theophylline 3.7. Gentisic acid-induced relaxation was markedly reduced (24 ± 7.0, 43 ± 3.9 and 78 ± 5.6%) in preparations with elevated potassium concentration in the medium (20, 40 or 80 mM, respectively). Tetraethylammonium (100 µM), a nonselective blocker of the potassium channels, partially inhibited the relaxation response to gentisic acid, while 4-AP (10 µM), a blocker of the voltage potassium channel, inhibited gentisic acid-induced relaxation by 41 ± 12%. Glibenclamide (1 or 3 µM), at a concentration which markedly inhibited the relaxation induced by the opener of ATP-sensitive K+ channels, levcromakalim, had no effect on the relaxation induced by gentisic acid. Charybdotoxin (0.1 or 0.3 µM), a selective blocker of the large-conductance Ca2+-activated K+ channels, caused rightward shifts (6- and 7-fold) of the gentisic acid concentration-relaxation curve. L-N G-nitroarginine (100 µM), a NO synthase inhibitor, had no effect on the relaxant effect of gentisic acid, and caused a slight displacement to the right in the relaxant effect of the gentisic acid curve at 300 µM, while methylene blue (10 or 30 µM) or ODQ (1 µM), the inhibitors of soluble guanylate cyclase, all failed to affect gentisic acid-induced relaxation. D-P-Cl-Phe6,Leu17[VIP] (0.1 µM), a VIP receptor antagonist, significantly inhibited (37 ± 7%) relaxation induced by gentisic acid, whereas CGRP (8-37) (0.1 µM), a CGRP antagonist, only slightly enhanced the action of gentisic acid. Taken together, these results provide functional evidence for the direct activation of voltage and large-conductance Ca+2-activated K+ channels, or indirect modulation of potassium channels induced by VIP receptors and accounts for the predominant relaxation response caused by gentisic acid in the guinea pig trachea.

Many studies have reported obvious seasonal differences in the intestinal flora of rats, and this stable distribution of the seasonal flora helps in maintaining the normal physiological function of the host. However, the mechanism underlying these seasonal differences in intestinal flora remains unclear. To explore the correlation among seasonal factors and intestinal water metabolism and intestinal flora, 20 Sprague Dawley (SD) rats were divided into spring, summer, autumn, and winter groups. The environment for the four seasons was simulated using the Balanced Temperature and Humidity Control system. The intestinal water metabolism was evaluated by determining the intestinal transmission function, fecal water content, water content of colonic tissue, and the colonic expression levels of AQP3, AQP4, and AQP8. The composition and relative abundance of intestinal microflora in rats in each season were assessed through 16S rDNA amplifier sequencing, and the relationship between the dominant flora and intestinal water metabolism in each season was analyzed using Spearman correlation analysis. The high temperature and humidity season could lead to an increase in intestinal water metabolism and intestinal water content in rats, whereas the low temperature and humidity season could lead to a decrease, which was closely related to the change in microflora. To explore the molecular mechanism of seasonal changes in intestinal water metabolism, the concentration of colonic 5-HT, VIP, cAMP, and PKA associated with intestinal water metabolism in rats were also examined. Seasonal changes could affect the concentration of colonic 5-HT and VIP in rats, and then regulate AQPs through cAMP/PKA pathway to affect the intestinal water metabolism. These results suggest that seasonal factors affect the level of intestinal water metabolism in rats and result in seasonal differences in intestinal flora., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Sun, Wang, Ma, Shi, Wang, Zhang, Wang and Liu.)

Background: Gastrointestinal (GI) functions are controlled by the enteric nervous system (ENS) in vertebrates, but data on snakes are scarce, as most studies were done in mammals. However, the feeding of many snakes, including Crotalus atrox, is in strong contrast with mammals, as it consumes an immense, intact prey that is forwarded, stored, and processed by the GI tract. We performed immunohistochemistry in different regions of the GI tract to assess the neuronal density and to quantify cholinergic, nitrergic, and VIPergic enteric neurons. We recorded motility patterns and determined the role of different neurotransmitters in the control of motility. Neuroimaging experiments complemented motility findings., Results: A well-developed ganglionated myenteric plexus (MP) was found in the oesophagus, stomach, and small and large intestines. In the submucous plexus (SMP) most neurons were scattered individually without forming ganglia. The lowest number of neurons was present in the SMP of the proximal colon, while the highest was in the MP of the oesophagus. The total number of neurons in the ENS was estimated to be approx. 1.5 million. In all regions of the SMP except for the oesophagus more nitric oxide synthase+ than choline-acetyltransferase (ChAT)+ neurons were counted, while in the MP ChAT+ neurons dominated. In the SMP most nerve cells were VIP+, contrary to the MP, where numerous VIP+ nerve fibers but hardly any VIP+ neuronal cell bodies were seen. Regular contractions were observed in muscle strips from the distal stomach, but not from the proximal stomach or the colon. We identified acetylcholine as the main excitatory and nitric oxide as the main inhibitory neurotransmitter. Furthermore, 5-HT and dopamine stimulated, while VIP and the ß-receptor-agonist isoproterenol inhibited motility. ATP had only a minor inhibitory effect. Nerve-evoked contractile responses were sodium-dependent, insensitive to tetrodotoxin (TTX), but sensitive to lidocaine, supported by neuroimaging experiments., Conclusions: The structure of the ENS, and patterns of gastric and colonic contractile activity of Crotalus atrox are strikingly different from mammalian models. However, the main excitatory and inhibitory pathways appear to be conserved. Future studies have to explore how the observed differences are an adaptation to the particular feeding strategy of the snake., (© 2023. The Author(s).)

Plant viral nanoparticles (VNPs) have become an attractive platform for the development of novel nanotools in the last years because of their safety, inexpensive production, and straightforward functionalization. Turnip mosaic virus (TuMV) is one example of a plant-based VNP used as a nanobiotechnological platform either as virions or as virus-like particles (VLPs). Their functionalization mainly consists of coating their surface with the molecules of interest via chemical conjugation or genetic fusion. However, because of their limitations, these two methods sometimes result in non-viable constructs. In this paper, we applied the SpyTag/SpyCatcher technology as an alternative for the functionalization of TuMV VLPs with peptides and proteins. We chose as molecules of interest the green fluorescent protein (GFP) because of its good traceability, as well as the vasoactive intestinal peptide (VIP), given the previous unsuccessful attempts to functionalize TuMV VNPs by other methods. The successful conjugation of VLPs to GFP and VIP using SpyTag/SpyCatcher was confirmed through Western blot and electron microscopy. Moreover, the isopeptide bond between SpyTag and SpyCatcher occurred in vivo in co-agroinfiltrated Nicotiana benthamiana plants. These results demonstrated that SpyTag/SpyCatcher improves TuMV functionalization compared with previous approaches, thus implying the expansion of the application of the technology to elongated flexuous VNPs.

In this review, we discuss sympathetic regulation in normal and diabetic wound healing. Experimental denervation studies have confirmed that sympathetic nerve endings in skin have an important and complex role in wound healing. Vasoconstrictor neurons secrete norepinephrine (NE) and neuropeptide Y (NPY). Both mediators decrease blood flow and interact with inflammatory cells and keratinocytes. NE acts in an ambiguous way depending on receptor type. Beta2-adrenoceptors could be activated near sympathetic endings; they suppress inflammation and re-epithelialization. Alpha1- and alpha2-adrenoceptors induce inflammation and activate keratinocytes. Sudomotor neurons secrete acetylcholine (ACh) and vasoactive intestinal peptide (VIP). Both induce vasodilatation, angiogenesis, inflammation, keratinocytes proliferation and migration. In healthy skin, all effects are important for successful healing. In treatment of diabetic ulcers, mediator balance could be shifted in different ways. Beta2-adrenoceptors blockade and nicotinic ACh receptors activation are the most promising directions in treatment of diabetic ulcers with neuropathy, but they require further research.

Introduction: The available literature provides relatively little information on the morphology of the autonomic head ganglia in rodents including their neurochemical codding., Material and Methods: Morphological investigations of the otic ganglion of the chinchilla were performed using the modified acetylcholinesterase method. The cellular structure was investigated with histological techniques and neurochemical properties were studied with the double-labelling immunofluorescence method., Results: Macromorphological investigations allowed the otic ganglion to be identified as a compact, oval agglomeration of neurons and nerve fibers. Multidimensional cross-sections revealed densely arranged neuronal perikarya and two populations of nerve cells differing in size were distinguished. The large cells (40-50 μm) accounted for about 80% of the neurons in the cross-sections. Moreover, a small number of intraganglionic nerve fibers was observed. Immunohistochemical staining revealed that over 85% of the neuronal cell bodies in the otic ganglion contained immunoreactivity to VAChT or ChAT. VIP-immunoreactive perikarya comprised approximately 10% of the ganglionic cells. Double staining revealed the presence of VAChT+ and NOS+ neurons which amounted to about 45% of the nerve cells in the otic ganglion. NOS+ only perikarya comprised approx. 15% of all the neurons. Immunoreactivity to enkephalins, substance P, somatostatin, and galanin was expressed in single nerve cell bodies and nerve fibers except numerous substance P+ intraganglionic nerve fibers. Some of them were stained also for CGRP. Single neurons stained for tyroxine hydroxylase., Conclusions: Our results, compared with findings in other rodent species suggest the existence of interspecies differences in the morphology, cellular structure, and immunohistochemical properties of the head autonomic ganglia in mammals.

A high-performance insulation solution, such as vacuum insulation panel (VIP) reduces heat losses in a retrofitted building envelope. However, discontinuity of insulation material causes thermal bridges. A significant thermal bridge effect at the edge of VIP must be taken into account in the overall heat transfer coefficient ( U -value) calculation; but is often omitted due to difficulties especially with numerical calculations. This study describes a modeling approach used to accurately evaluate the effect of thermal bridges on the overall U -value of building envelope. The thermal bridge and U -value were modeled and computed respectively using DesignBuilder which is based on EnergyPlus dynamic simulation engine. Correlation was drawn between experimentally determined U -value of VIP retrofitted building walls and the principal computation parameter. [ABSTRACT FROM AUTHOR]

The present study reports the use Mg n Co (n = 1–10) hybrid nanoclusters as hydrogen storage using density functional theory (DFT) calculation method. From the variation of the thermodynamic parameters of the clusters Mg 4 Co and Mg 6 Co are found stable in the series, whereas, after absorption of hydrogen, the higher stability shifted to H 2 -Mg 5 Co. It is found that after reaction with the cluster, hydrogen atoms adsorbed with Co atom in Mg n Co clusters to form Mg n CoH 2 that gives a better option in hydrogen catalysis. By the calculated values of chemisorptions and physisorptions energies; VIP and VEA parameters, we found Mg 5 Co can be used as effective hydrogen catalysis. Calculated chemisorptions energy of the H 2 -Mg 5 Co cluster is found maximum in the series. The calculated activation barrier energy of H 2 -Mg 5 Co has been verified by the study of intrinsic reaction coordinates (IRC) pathway between Mg 5 Co and H 2 . [ABSTRACT FROM AUTHOR]

Amacrine cells (ACs) are the most diverse class of neurons in the retina. The variety of signals provided by ACs allows the retina to encode a wide range of visual features. Of the 30–50 AC types in mammalian species, few have been studied in detail. Here, we combine genetic and viral strategies to identify and to characterize morphologically three vasoactive intestinal polypeptide-expressing GABAergic AC types (VIP1-, VIP2-, and VIP3-ACs) in mice. Somata of VIP1- and VIP2-ACs reside in the inner nuclear layer and somata of VIP3-ACs in the ganglion cell layer, and they show asymmetric distributions along the dorsoventral axis of the retina. Neurite arbors of VIP-ACs differ in size (VIP1-ACs ≈ VIP3-ACs > VIP2-ACs) and stratify in distinct sublaminae of the inner plexiform layer. To analyze light responses and underlying synaptic inputs, we target VIP-ACs under 2-photon guidance for patch-clamp recordings. VIP1-ACs depolarize strongly to light increments (ON) over a wide range of stimulus sizes but show size-selective responses to light decrements (OFF), depolarizing to small and hyperpolarizing to large stimuli. The switch in polarity of OFF responses is caused by pre- and postsynaptic surround inhibition. VIP2- and VIP3-ACs both show small depolarizations to ON stimuli and large hyperpolarizations to OFF stimuli but differ in their spatial response profiles. Depolarizations are caused by ON excitation outweighing ON inhibition, whereas hyperpolarizations result from pre- and postsynaptic OFF-ON crossover inhibition. VIP1-, VIP2-, and VIP3-ACs thus differ in response polarity and spatial tuning and contribute to the diversity of inhibitory and neuromodulatory signals in the retina. [ABSTRACT FROM AUTHOR]

Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties. [ABSTRACT FROM AUTHOR]

We compared the effect of VIP on human blood monocytes infected with Salmonella typhimurium 4/74 or stimulated with LPS. VIP (10 −7 M) increased monocyte viability by 24% and 9% when cultured for 24 h with 4/74 or Salmonella LPS (100 ng/ml), respectively. Significantly increased ( P < 0.05) numbers of 4/74 were also recovered from monocytes co-cultured with VIP after 6 h post-infection (pi) and this remained high after 24 h pi. Both 4/74 and LPS increased ( P < 0.05) the concentration of TNF-α, IL-1β and IL-6 measured in monocyte supernatants. However, LPS induced this effect more rapidly while, with the exception of IL-6, 4/74 induced higher concentrations ( P < 0.05). VIP significantly decreased ( P < 0.05) TNF-α and IL-1β production by 4/74-infected monocytes after 6 pi, but only after 24 h in LPS-cultured monocytes. This trend was reversed for IL-6 production. However, TNF-α and IL-1β production by 4/74-infected monocytes, cultured with VIP, still remained higher ( P < 0.05) than concentrations measured in supernatants cultured only with LPS. VIP also increased ( P < 0.05) production of anti-inflammatory IL-10 in both 4/74 and LPS cultures after 24 h. We also show a differential effect of VIP on the expression of TNFα and IL-6 receptors, since VIP was only able to decreased expression in LPS-stimulated monocytes but not in 4/74-infected monocytes. In conclusion, we show a differential effect of VIP on human monocytes infected with virulent Salmonella or stimulated with LPS. Our study suggests that the use of VIP in bacteraemia and/or sepsis may be limited to an adjunctive therapy to antibiotic treatment. [ABSTRACT FROM AUTHOR]

Recently a new parameter to infer variable importance in orthogonal projections to latent structures (OPLS) was presented. Called OPLS-VIP (variable influence on projection), this parameter is here applied in multivariate time series analysis to achieve an improved diagnosis of process dynamics. To this end, OPLS-VIP has been tested in three real-world industrial data sets; the first data set corresponds to a pulp manufacturing process using a continuous digester, the second one involves data from an industrial heater that experienced problems, and the third data set contains measures of the chemical oxygen demand into the effluent of a newsprint mill. The outcomes obtained using OPLS-VIP are benchmarked against classical PLS-VIP results. It is demonstrated how OPLS-VIP provides a better diagnosis and understanding of the time series behavior than PLS-VIP. [ABSTRACT FROM AUTHOR]

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As a way to understand vegetation changes, trend analysis on NDVI (normalized difference vegetation index) time series data have been widely performed at regional to global scales. However, most long-term NDVI datasets are based upon multiple sensor systems and unsuccessful corrections related to sensor shifts potentially introduce substantial uncertainties and artifacts in the analysis of trends. The temporal consistency of NDVI datasets should therefore be evaluated before performing trend analysis to obtain reliable results. In this study we analyze the temporal consistency of multi-sensor NDVI time series by analyzing the co-occurrence between breaks in the NDVI time series and sensor shifts from GIMMS3g (Global Inventory Modeling and Mapping Studies 3rd generation), VIP3 (Vegetation Index and Phenology version 3), LTDR4 (Long Term Data Record version 4) and SPOT-VGT (Système Pour l'Observation de la Terre VEGETATION). Single sensor time series from MODIS (MODerate Resolution Imaging Spectroradiometer) Terra and Aqua are used as reference datasets. The global land surface is divided into six regions according to the world humidity zones and averaged NDVI time series in each region are analyzed separately using a multiple structural change detection approach. We find that artifacts exist in the VIP3 and LTDR4 NDVI datasets with an abrupt shift detected in all humidity zones coinciding with the shift from NOAA-9 to NOAA-11 in 1988 and that orbital drift effects are evident in arid regions, potentially introducing uncertainties in NDVI trend analysis. Platform/sensor change from VGT-1 to VGT-2 is found to cause a significant positive break in the SPOT-VGT NDVI time series. Potential artifacts exist in humid, dry-subhumid, semi-arid and hyper-arid regions of GIMMS3g NDVI, whereas no signs of artifacts are found in the arid region. Although temporal consistency throughout all examined datasets increases after 2000 due to the usage of advanced platforms and sensors, variations in NDVI values from 2010 to 2011 still result in different trends at global and regional scales. [ABSTRACT FROM AUTHOR]

Disturbances in the sleep/wake cycle are prevalent in patients with Rett syndrome (RTT). We sought to determine whether the circadian system is disrupted in a RTT model, Mecp2 −/y mice. We found that MeCP2 mutants showed decreased strength and precision of daily rhythms of activity coupled with extremely fragmented sleep. The central circadian clock (suprachiasmatic nucleus) exhibited significant reduction in the number of neurons expressing vasoactive intestinal peptide (VIP) as well as compromised spontaneous neural activity. The molecular clockwork was disrupted both centrally in the SCN and in peripheral organs, indicating a general disorganization of the circadian system. Disruption of the molecular clockwork was observed in fibroblasts of RTT patients. Finally, MeCP2 mutant mice were vulnerable to circadian disruption as chronic jet lag accelerated mortality. Our finds suggest an integral role of MeCP2 in the circadian timing system and provides a possible mechanistic explanation for the sleep/wake distrubances observed in RTT patients. The work raises the possibility that RTT patients may benefit from a temporally structured environment. [ABSTRACT FROM AUTHOR]

Two experiments examined the expression of gonadotrophin-releasing and inhibiting hormones (Gn RH-I, Gn RH- II and Gn IH), neuropeptide Y ( NPY) and vasoactive intestinal peptide ( VIP) in subtropical Indian weaver birds, which demonstrate relative photorefractoriness. Experiment 1 measured peptide expression levels in the form of immunoreactive (-IR) cells, percentage cell area and cell optical density in the preoptic area (Gn RH-I), midbrain (Gn RH- II), paraventricular nucleus (Gn IH), mediobasal hypothalamus [dorsomedial hypothalamus ( DMH), infundibular complex ( INc), NPY and VIP] and lateral septal organ ( VIP) during the progressive, breeding, regressive and nonbreeding phases of the annual reproductive cycle. Gn RH-I was decreased in the nonbreeding and VIP was increased in INc in the breeding and regressive states. Gn RH- II and NPY levels did not differ between the testicular phases. Double-labelled immunohistochemistry (IHC) revealed a close association between the Gn RH/Gn IH, Gn RH/ NPY, Gn RH/ VIP and Gn IH/ NPY peptide systems, implicating them interacting and playing roles in the reproductive regulation in weaver birds. Experiment 2 further measured these peptide levels in the middle of day and night in weaver birds that were maintained under short days (8 : 16 h light /dark cycle; photosensitive), exposed to ten long days (16 : 8 h light /dark cycle; photostimulated) or maintained for approximately 2 years on a 16 : 8 h light /dark cycle (photorefractory). Reproductively immature testes in these groups precluded the possible effect of an enhanced gonadal feedback on the hypothalamic peptide expression. There were group differences in the Gn RH-I (not Gn RH- II), Gn IH, NPY and VIP immunoreactivity, albeit with variations in immunoreactivity measures in the present study. These results, which are consistent with those reported in birds with relative photorefractoriness, show the distribution and possibly a complex interaction of key neuropeptides in the regulation of the annual reproductive cycle in Indian weaver birds. [ABSTRACT FROM AUTHOR]

Abstract Aim: The aim of this article is to determine vasoactive intestinal peptide (VIP) levels outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine (CM). Methods:Women older than 17 and diagnosed as CM were recruited. Matched healthy women with no headache history and women with episodic migraine (EM) served as control groups, together with a series of patients with episodic cluster headache in a pain-free period. VIP levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack, the patients having taken no symptomatic medication the day before. For ethical reasons, preventives were not stopped. Results: We assessed plasma samples from 119 women with CM, 33 healthy women, 51 matched women with EM and 18 patients (16 males) with cluster headache matched for age. VIP levels were significantly increased in CM (165.1 pg/ml) as compared to control healthy women (88.5 pg/ml) and episodic cluster headache patients (101.1 pg/ml). VIP levels in EM (134.9 pg/ml) were significantly higher compared to controls and numerically lower than those of CM. Thresholds of 71.8 and 164.5 pg/ml optimized the sensitivity and specificity to differentiate CM from healthy controls and EM, respectively. Variables such as age, CM duration, the presence of aura, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption or kind of preventive treatment did not significantly influence VIP levels. Conclusion: Increased interictal VIP level measured in peripheral blood could be a biomarker helping in CM diagnosis, though it does not clearly differentiate between EM and CM. [ABSTRACT FROM AUTHOR]