Search

Physalis peruviana L. (golden berry) fruit is attractive for its many health benefits, associated with the presence of anti-inflammatory and antioxidant compounds. High fruit consumption has been associated with a lower risk of developing chronic non-communicable diseases. This work evaluated the anti-inflammatory potential of ten fruits cultivated in Colombia, determining their capacity to inhibit ⋅NO production in LPS-activated RAW 264.7 macrophages. The most active extracts were evaluated for their effect on the production of IL-1β, IL-6, TNF-α, and PGE2. Golden berry was the most active extract, so its immunomodulatory effect was evaluated in a model of DSS-induced colitis in BALB/c mice. Dietary supplementation with golden berry attenuates the pathological symptoms of colitis. This effect may be associated with the inhibition of neutrophil infiltration and impacts on the production of IL-6, IL-1β, IL-10, TNF-α, and ROS. Our results suggest that consistently consuming golden berries could benefit intestinal inflammation.

Abstract Beyond the catastrophic environmental effects of large (>1 km3) volcanic landslides, their impact on underlying magmatic systems remains unclear. Chemical variations in post-collapse volcanic products, alongside dramatic eruptive behaviour transitions reported from several volcanoes, imply that surface unloading directly influences subsurface magmatic processes. By combining petrologic data with magma ascent models, we track the post-collapse (

Tinnitus is the phantom perception of sound that has no external source. A neurological signature of tinnitus, and the frequently associated hyperacusis, is an imbalance between excitatory and inhibitory activity in the central auditory system (CAS), leading to dysregulated network excitability. The large conductance, calcium-activated potassium (BK) channel is a key player in pre- and post-synaptic excitability through its mediation of K+ currents. Changes in BK channel activity are associated with aberrant network activity in sensory regions of the CNS, raising the possibility that BK channel modulation could regulate activity associated with tinnitus and hyperacusis. To test whether BK channel openers are able to suppress biomarkers of drug-induced tinnitus and hyperacusis, the 1,3,4 oxadiazole BMS-191011 was given to young adult CBA mice that had been administered 250 mg/kg sodium salicylate (SS). Systemic treatment with BMS-191011 reduced behavioral manifestations of SS-induced tinnitus, but not hyperacusis, probed via the gap-in-noise startle response method. Systemic BMS-191011 treatment did not influence SS-induced increases in auditory brainstem response functions, but local application at the inferior colliculus did reverse SS-suppressed spontaneous activity, particularly in the frequency region of the tinnitus percept. Thus, action of BMS-191011 in the inferior colliculus may contribute to the reduction in behaviorally measured tinnitus. Together, these findings support the utility of BK channel openers in reducing central auditory processing changes associated with the formation of the tinnitus percept.

BackgroundSince many of the risk factors for cognitive decline can be modified by diet, the study of nutrition and its relationships with cognitive status in aging has increased considerably in recent years. However, there are hardly any studies that have assessed cognitive status using a comprehensive set of neuropsychological tests along with measures of functional capacity and mood and that have related it to nutritional status measured from several nutritional parameters that have shown its relationships with cognitive function.ObjectiveTo test the differences in depressive symptomatology and in several measures of nutritional status between three groups classified according to their cognitive status (CS hereafter).MethodOne hundred thirteen participants from nursing homes in Galicia, Spain, underwent a comprehensive neuropsychological examination, including a general screening test (MMSE) and tests for different cognitive domains along with measures of activities of daily living (ADL) and assessment of depressive symptomatology (GDS-SF). According to established clinical criteria, participants were divided into three CS groups, Cognitively Intact (CI), Mild Cognitive Impairment (MCI), and All-Cause Dementia (ACD). Nutritional status was also examined using blood-derived measures, body mass index (BMI) and a nutritional screening test (MNA-SF). Differences between CS groups in all nutritional variables were studied by one-way ANOVAs with post-hoc Bonferroni correction or Kruskal-Wallis with Games-Howell post-hoc correction when appropriate. Multinomial logistic regression was also applied to test the association between nutritional variables and CS.ResultsDifferences between CS groups were statistically significant for depressive symptomatology, vitamin A and D, albumin, selenium (Se), uric acid (UA), and BMI. The results of multinomial logistic regression found positive associations between groups with better CS and higher concentrations of vitamins A and D, transthyretin (TTR), albumin, Se, and UA, while negative associations were found for BMI.ConclusionHigher serum levels of vitamin A, vitamin D, TTR, albumin, Se, and UA could act as protective factors against cognitive decline, whereas higher BMI could act as a risk factor.

Staphylococcus aureus remains a pathogen of high concern in public health programs worldwide due to antibiotic resistance and emergence of highly virulent strains. Many phytochemicals have demonstrated activity against S. aureus and other Gram-positive bacteria, but the minimum inhibitory concentration (MIC) values comparable to commonly used antibiotics are needed. In the present study, bio-guided fractionation of the ethanol extract of seeds of Mammea americana L. (Calophyllaceae) throughout the antibacterial activity, against S. aureus strains that are sensitive and resistant to methicillin, led to the isolation of four coumarins identified as mammea B/BA, mammea B/BC, mammea A/AA cyclo D and mammea A/AA cyclo F, and a mixture of mammea B/BA cyclo F plus mammea B/BD cyclo F. The extract inhibited the growth of S. aureus with MIC values of 2–4 μg/ml and Mammea B/BA (MaBBA) presented MIC values in a range between 0.5 and 1.0 μg/ml in six methicillin-sensitive strains and eight methicillin-resistant strains evaluated. We consider MaBBA the most potent of all mammea coumarins reported to date, according to the literature review carried out at the time of writing of this article. Toxicity assessment in vivo against the nematode Caenorhabditis elegans and in vitro against human fibroblasts of the extract and the compound MaBBA indicated that both had low toxicity.

The term moonlighting proteins refers to those proteins that present alternative functions performed by a single polypeptide chain acquired throughout evolution (called canonical and moonlighting, respectively). Over 78% of moonlighting proteins are involved in human diseases, 48% are targeted by current drugs, and over 25% of them are involved in the virulence of pathogenic microorganisms. These facts encouraged us to study the link between the functions of moonlighting proteins and disease. We found a large number of moonlighting functions activated by pathological conditions that are highly involved in disease development and progression. The factors that activate some moonlighting functions take place only in pathological conditions, such as specific cellular translocations or changes in protein structure. Some moonlighting functions are involved in disease promotion while others are involved in curbing it. The disease-impairing moonlighting functions attempt to restore the homeostasis, or to reduce the damage linked to the imbalance caused by the disease. The disease-promoting moonlighting functions primarily involve the immune system, mesenchyme cross-talk, or excessive tissue proliferation. We often find moonlighting functions linked to the canonical function in a pathological context. Moonlighting functions are especially coordinated in inflammation and cancer. Wound healing and epithelial to mesenchymal transition are very representative. They involve multiple moonlighting proteins with a different role in each phase of the process, contributing to the current-phase phenotype or promoting a phase switch, mitigating the damage or intensifying the remodeling. All of this implies a new level of complexity in the study of pathology genesis, progression, and treatment. The specific protein function involved in a patient’s progress or that is affected by a drug must be elucidated for the correct treatment of diseases.

Glacially- and magmatically-derived seismic events have been noted to heavily overlap in characteristics, thus there exists the potential for false-alarms or missed warnings at ice-covered volcanoes. Here we present the first study to specifically target icequakes at an ice-covered volcano in Southern Chile. Two months of broadband seismic data collected at Llaima volcano in 2015 were analyzed in order to quantify, characterize, and locate glacially-derived seismic events at one of the most active ice-covered volcanoes in the region. We find over 1,000 repeating seismic events across 11 families, the largest of which contains 397 events. Approximate locations and characteristics of the largest families lead us to conclude that these events were derived from persistent stick-slip motion along the ice-rock interface at the base of a glacier near the volcano summit. These results have implications for future seismic monitoring at Llaima volcano and other ice-covered active volcanoes in the region.

In this article two different controllers for the stabilization of a fractional-order discrete system in the left Caputo discrete delta operator sense are given. The first one acts by a fractional proportional pulse control, the second acts by a fractional feedback control. These controllers are applied to fractional-order chaotic discrete dynamical systems to obtain their stability and also we show a comparison with the integer order dynamical systems stability. Some simulations are presented for the fractional logistic map and the fractional Henon map.

Volcanic cones are frequently near their gravitational stability limit, which can lead to lateral collapse of the edifice, causing extensive environmental impact, property damage, and loss of life. Here, we examine lateral collapses in mafic arc volcanoes, which are relatively structurally simple edifices dominated by a narrow compositional range from basalts to basaltic andesites. This still encompasses a broad range of volcano dimensions, but the magma types erupted in these systems represent the most abundant type of volcanism on Earth and rocky planets. Their often high magma output rates can result in rapid construction of gravitationally unstable edifices susceptible both to small landslides but also to much larger-scale catastrophic lateral collapses. Although recent studies of basaltic shield volcanoes provide insights on the largest subaerial lateral collapses on Earth, the occurrence of lateral collapses in mafic arc volcanoes lacks a systematic description, and the features that make such structures susceptible to failure has not been treated in depth. In this review, we address whether distinct characteristics lead to the failure of mafic arc volcanoes, or whether their propensity to collapse is no different to failures in volcanoes dominated by intermediate (i.e., andesitic-dacitic) or silicic (i.e., rhyolitic) compositions? We provide a general overview on the stability of mafic arc edifices, their potential for lateral collapse, and the overall impact of large-scale sector collapse processes on the development of mafic magmatic systems, eruptive style and the surrounding landscape. Both historical accounts and geological evidence provide convincing proofs of recurrent (and even repetitive) large-scale (>0.5 km3) lateral failure of mafic arc volcanoes. The main factors contributing to edifice instability in these volcanoes are: (1) frequent sheet-like intrusions accompanied by intense deformation and seismicity; (2) shallow hydrothermal systems weakening basaltic rocks and reducing their overall strength; (3) large edifices with slopes near the critical angle; (4) distribution along fault systems, especially in transtensional settings, and; (5) susceptibility to other external forces such as climate change. These factors are not exclusive of mafic volcanoes, but probably enhanced by the rapid building of such edifices.

Volatile contents in melt inclusions can be used to unravel magma migration and degassing. Here, the authors use olivine chronometry and melt inclusion data from the 2008 Llaima eruption and find that magma intrusion occurred 4 years before the eruption and reached a depth of 3–4 km, 6 months before the eruption.

Resuming erupting activity at volcanoes that have been long quiescent poses a significant challenge to hazard assessment, as it require assessment of whether the change in activity is an isolated event or the beginning of a new eruptive sequence. Such inception is often poorly characterised as quiescent volcanoes tend to be poorly equipped and not extensively monitored, especially with respect to gas geochemistry. Here, we report gas composition and flux measurements from a newly opened vent at the very onset of eruptive activity at the Nevados de Chillán volcanic complex (Chile) in January-February 2016. The molar proportions of H2O, CO2, SO2, H2S and H2 gases are found to be 98.4, 0.97, 0.11, 0.01 and 0.5 mol% respectively. The mean SO2 flux recorded in early February 2016 during periods of eruptive discharge amounts to 0.4-0.6 kg s-1. Our results indicate that the new vent opening was propelled by magmatic gases, triggering repeated eruptions. Ash particles ejected by the first blast of 8 January are dominated by lithic fragments of dacitic composition. By contrast the ash ejected in a subsequent eruption contains both lithic fragments of dense dacite, and a fresher, sparsely vesicular material of basaltic andesite composition. By October 2017 the ejected ash is back to being dominated by the dense dacitic lithic material. Together with the seismic and deformation record, these observations point to the explosive activity resulting from a small intrusion of basaltic to andesitic magma at shallow level. The fate of this magma, whether stalling or eventually triggering a magmatic eruption, remains to be seen, but current observations suggest the former is most likely.

Acute pancreatitis is an inflammatory process of the pancreatic gland that may lead to dysregulation of the trans-sulfuration pathway. The aims of this work were firstly to study the methionine cycle as well as the trans-sulfuration pathway using metabolomic and proteomic approaches identifying the causes of this dysregulation in an experimental model of acute pancreatitis; and secondly to reveal the effects of S-adenosylmethionine administration on these pathways. Acute pancreatitis was induced by cerulein in mice, and a group of animals received S-adenosylmethionine treatment. Cerulein-induced acute pancreatitis rapidly caused marked depletion of methionine, S-adenosylmethionine, 5′-methylthioadenosine, cystathionine, cysteine, and glutathione levels in pancreas, but S-adenosylhomocysteine and homocysteine remained unchanged. Protein steady-state levels of S-adenosylhomocysteine-hydrolase and cystathionine gamma-lyase diminished but methylthioadenosine phosphorylase levels increased in pancreas with acute pancreatitis. Although cystathionine β-synthase protein levels did not change with acute pancreatitis, Nos2 mRNA and protein levels were markedly up-regulated and caused tyrosine nitration of cystathionine β-synthase in pancreas. S-adenosylmethionine administration enhanced Nos2 mRNA expression and cystathionine β-synthase nitration and triggered homocysteine accumulation in acute pancreatitis. Furthermore, S-adenosylmethionine administration promoted enrichment of the euchromatin marker H3K4me3 in the promoters of Tnf-α, Il-6, and Nos2 and enhanced the mRNA up-regulation of these genes. Accordingly, S-adenosylmethionine administration increased inflammatory infiltrate and edema in pancreas with acute pancreatitis. In conclusion, tyrosine-nitration of cystathionine β-synthase blockades the trans-sulfuration pathway in acute pancreatitis promoting homocysteine accumulation upon S-adenosylmethionine treatment. Keywords: Acute inflammation, S-adenosylmethionine, Homocysteine, Cystathionine β-synthase, Nitrosative stress

Moonlighting and multitasking proteins refer to proteins with two or more functions performed by a single polypeptide chain. An amazing example of the Gain of Function (GoF) phenomenon of these proteins is that 25% of the moonlighting functions of our Multitasking Proteins Database (MultitaskProtDB-II) are related to pathogen virulence activity. Moreover, they usually have a canonical function belonging to highly conserved ancestral key functions, and their moonlighting functions are often involved in inducing extracellular matrix (ECM) protein remodeling. There are three main questions in the context of moonlighting proteins in pathogen virulence: (A) Why are a high percentage of pathogen moonlighting proteins involved in virulence? (B) Why do most of the canonical functions of these moonlighting proteins belong to primary metabolism? Moreover, why are they common in many pathogen species? (C) How are these different protein sequences and structures able to bind the same set of host ECM protein targets, mainly plasminogen (PLG), and colonize host tissues? By means of an extensive bioinformatics analysis, we suggest answers and approaches to these questions. There are three main ideas derived from the work: first, moonlighting proteins are not good candidates for vaccines. Second, several motifs that might be important in the adhesion to the ECM were identified. Third, an overrepresentation of GO codes related with virulence in moonlighting proteins were seen.

Detecting pathogens and mounting immune responses upon infection is crucial for animal health. However, these responses come at a high metabolic price (McKean and Lazzaro, 2011, Kominsky et al., 2010), and avoiding pathogens before infection may be advantageous. The bacterial endotoxins lipopolysaccharides (LPS) are important immune system infection cues (Abbas et al., 2014), but it remains unknown whether animals possess sensory mechanisms to detect them prior to infection. Here we show that Drosophila melanogaster display strong aversive responses to LPS and that gustatory neurons expressing Gr66a bitter receptors mediate avoidance of LPS in feeding and egg laying assays. We found the expression of the chemosensory cation channel dTRPA1 in these cells to be necessary and sufficient for LPS avoidance. Furthermore, LPS stimulates Drosophila neurons in a TRPA1-dependent manner and activates exogenous dTRPA1 channels in human cells. Our findings demonstrate that flies detect bacterial endotoxins via a gustatory pathway through TRPA1 activation as conserved molecular mechanism.

Colorectal cancer (CRC) is a disease with high incidence and mortality, constituting the fourth most common cause of death from cancer worldwide. Naphthoquinones are attractive compounds due to their biological and structural properties. In this work, 36 naphthoquinone derivatives were synthesized and their activity evaluated against HT-29 cells. Overall, high to moderate anti-proliferative activity was observed in most members of the series, with 15 compounds classified as active (1.73 < IC50 < 18.11 μM). The naphtho[2,3-b]thiophene-4,9-dione analogs showed potent cytotoxicity, 8-hydroxy-2-(thiophen-2-ylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione being the compound with the highest potency and selectivity. Our results suggest that the toxicity is improved in molecules with tricyclic naphtho[2,3-b]furan-4,9-dione and naphtho[2,3-b]thiophene-4,9-dione systems 2-substituted with an electron-withdrawing group. A 3D-QSAR study of comparative molecular field analysis (CoMFA) was carried out, resulting in the generation of a reliable model (r2 = 0.99 and q2 = 0.625). This model allowed proposing five new compounds with two-fold higher theoretical anti-proliferative activity, which would be worthwhile to synthesize and evaluate. Further investigations will be needed to determine the mechanism involved in the effect of most active compounds which are potential candidates for new anticancer agents.

The prognosis of hepatocellular carcinoma patients is usually poor, the size of tumors being a limiting factor for surgical treatments. Present results suggest that the overexpression of Gas1 (growth arrest specific 1) gene reduces the size, proliferating activity and malignancy of liver tumors. Mice developing diethylnitrosamine-induced hepatocellular carcinoma were subjected to hydrodynamic gene delivery to overexpress Gas1 in liver. This treatment significantly (p < 0.05) reduced the number of large tumors, while the difference in the total number of lesions was not significant. Moreover, the number of carcinoma foci in the liver and the number of lung metastases were reduced. These results are related with the finding that overexpression of Gas1 in Hepa 1-6 cells arrests cell cycle before S phase, with a significant (p < 0.01) and concomitant reduction in the expression of cyclin E2 gene. In addition, a triangular analysis of microarray data shows that Gas1 overexpression restores the transcription levels of 150 genes whose expression was affected in the diethylnitrosamine-induced tumors, thirteen of which are involved in the hedgehog signaling pathway. Since the in vivo Gas1 gene delivery to livers of mice carrying hepatocellular carcinoma reduces the size and proliferating activity of tumors, partially restoring the transcriptional profile of the liver, the present study opens promising insights towards a therapeutic approach for hepatocellular carcinoma.

The development of periodontal disease and dental caries is influenced by several factors, such as microorganisms of bacterial biofilm or commensal bacteria in the mouth. These microorganisms trigger inflammatory and immune responses in the host. Currently, medicinal plants are treatment options for these oral diseases. Mammea americana extracts have reported antimicrobial effects against several microorganisms. Nevertheless, this effect is unknown against oral bacteria. Therefore, the aim of this study was to evaluate the antibacterial effect of M. americana extract against Porphyromonas gingivalis and Streptococcus mutans. For this, an experimental study was conducted. Ethanolic extract was obtained from seeds of M. americana (one oil phase and one ethanolic phase). The strains of Porphyromonas gingivalis ATCC 33277 and Streptococcus mutans ATCC 25175 were exposed to this extract to evaluate its antibacterial effect. Antibacterial activity was observed with the two phases of M. americana extract on P. gingivalis and S. mutans with lower MICs (minimum inhibitory concentration). Also, bactericidal and bacteriostatic activity was detected against S. mutans, depending on the concentration of the extract, while on M. americana extract presented only bacteriostatic activity against P. gingivalis. These findings provide important and promising information allowing for further exploration in the future.

In this paper the author examines the tools for environmental protection within the European Community (EC), dating from the Treaty of Rome (1957) through to the European Community’s Fifth Program of Environmental Action, which includes proposals for up till the end of the century. Thus, the study covers the development of the budding environmental policy for Europe- first outlined in the 60’s, then continued on through the enlargement of the legal means featured in the Single Act(1986). For the first time in the EC by such Act, policies demanding environmental and consumer protection are introduced. The paper places further emphasis on the progress which the signing of the the Treaty of the European Union (1992) meant for EC environmental policy. Indeed, this Treaty regulates economic growth, as long as growth is accompanied by environmental protection and favors the quality of life. The Treaty also outlines measures designed to face regional and worldwide problems. This article highlights the repercussions that these regulations have upon existing Spanish codes as well as upon Spain’s position towardsenvironmental policy. Finally, the paper deals with issues contained in the European Community’s Fifth Program of Environmental Action spanning the years 1993-2000; Program carried out under the watchwords of sustainable development, and whose objectives are in accordance with both the report completed by the Global Commision on the Environment and Development and the conclusions drawn from the World Summit on the Environment in Rio de Janeiro (1992). This paper’s conclusions show that Europe’s community environmental policies have not, as yet, yielded satisfactory results.

BACKGROUND: Gas1 (growth arrest-specific 1) gene is known to inhibit cell proliferation in a variety of models, but its possible implication in regulating quiescence in adult tissues has not been examined to date. The knowledge of how Gas1 is regulated in quiescence may contribute to understand the deregulation occurring in neoplastic diseases. METHODOLOGY/PRINCIPAL FINDINGS: Gas1 expression has been studied in quiescent murine liver and during the naturally synchronized cell proliferation after partial hepatectomy. Chromatin immunoprecipitation at nucleosomal resolution (Nuc-ChIP) has been used to carry out the study preserving the in vivo conditions. Transcription has been assessed at real time by quantifying the presence of RNA polymerase II in coding regions (RNApol-ChIP). It has been found that Gas1 is expressed not only in quiescent liver but also at the cell cycle G(1)/S transition. The latter expression peak had not been previously reported. Two nucleosomes, flanking a nucleosome-free region, are positioned close to the transcription start site. Both nucleosomes slide in going from the active to the inactive state and vice versa. Nuc-ChIP analysis of the acquisition of histone epigenetic marks show distinctive features in both active states: H3K9ac and H3K4me2 are characteristic of transcription in G(0) and H4R3me2 in G(1)/S transition. Sequential-ChIP analysis revealed that the "repressing" mark H3K9me2 colocalize with several "activating" marks at nucleosome N-1 when Gas1 is actively transcribed suggesting a greater plasticity of epigenetic marks than proposed until now. The recruitment of chromatin-remodeling or modifying complexes also displayed distinct characteristics in quiescence and the G(1)/S transition. CONCLUSIONS/SIGNIFICANCE: The finding that Gas1 is transcribed at the G(1)/S transition suggests that the gene may exert a novel function during cell proliferation. Transcription of this gene is modulated by specific "activating" and "repressing" epigenetic marks, and by chromatin remodeling and histone modifying complexes recruitment, at specific nucleosomes in Gas1 promoter.

This work analyzes the problem of fixing GPS ellipsoidal heights by geoidal undulation effects. It studies some correction models that some institutes use for that purpose, here in Venezuela; testing them on a previously selected test network. Analyzing the results obtained on the different tests, comparing them with the height values of the points in the DCN system, with special emphasis on the differences between them. Conclusions and recommendations are presented to GPS users with respect to the advantages and disadvantages of each geoidal correction model.

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)