The aim of this study was to evaluate the Enterobacterial Repetitive Intergenic Consensus (ERIC-PCR) as a tool for molecular typing of C. pseudotuberculosis isolates from eight different hosts in ...twelve countries. Ninety-nine C. pseudotuberculosis field strains, one type strain (ATCC 19410T) and one vaccine strain (1002) were fingerprinted using the ERIC-1R and ERIC-2 primers, and the ERIC-1R+ERIC-2 primer pair. Twenty-nine different genotypes were generated by ERIC 1-PCR, 28 by ERIC 2-PCR and 35 by ERIC 1+2-PCR. The discriminatory index calculated for ERIC 1, ERIC 2, and ERIC 1+2-PCR was 0.89, 0.86, and 0.92, respectively. Epidemiological concordance was established for all ERIC-PCR assays. ERIC 1+2-PCR was defined as the best method based on suitability of the amplification patterns and discriminatory index. Minimal spanning tree for ERIC 1+2-PCR revealed three major clonal complexes and clustering around nitrate-positive (biovar Equi) and nitrate-negative (biovar Ovis) strains. Therefore, ERIC 1+2-PCR proved to be the best technique evaluated in this study for genotyping C. pseudotuberculosis strains, due to its usefulness for molecular epidemiology investigations.
Asthma is a chronic inflammatory disease that targeting lower airways, being characterized by bronchial smooth muscle hyper responsiveness and mucus hypersecretion. Asthma is considered the most ...common respiratory disease in the world, affecting approximately 235 million individuals. The main therapy sometimes fails to establish clinical improvement in patients, which leads to a constant search for new alternatives. Camphor is a transparent solid monoterpene with a strong aroma, which due to its high lipophilicity is insoluble in water. Nanostructured carrier systems have shown promise as a delivery system for lipophilic compounds such as monoterpenes. Therefore, the objective of this work was to evaluate the relaxant effect of nanoemulsified camphor (NEC), as well as the mechanism of action of that monoterpene, in isolated rat trachea. The results obtained demonstrated that NEC promote relaxation of the isolated rat trachea when smooth muscle contraction was induced by both carbachol (CCh) and KCl, presenting a pCE50 of 2.25 ± 0.27 and 3.30 ± 0.07, respectively. In the presence of dexamethasone (DEXA), tetraethylammonium (TEA), glibenclamide (GLIB), 1H-1,2,4-oxadiazole-4,3,-a-quinoxaline-1-one (ODQ) and ruthenium red (RR) there was a significant difference in at least one of the evaluated pharmacological parameters, such as concentration-response curves shape, Emax or pCE50.
As conclusion, NEC may be involved with β-adrenergic receptors, channels for K+ sensitive to ATP (KATP) or Channels for K+ opened by Ca2+ (KCa), increase in prostanoids and with receptor channel with transient potential (TRPv). In conclusion, β-adrenergic receptors, prostanoids, nitric oxide (NO), ATP-sensitive K+ channels (KATP), Ca2+-opened K+ channels (KCa), and transient receptor potential cation channel subfamily V (TRPV) are involved in the relaxing effect of NEC.
In addition, the mechanism of action of NEC may be involved with the signal transduction pathway Nitric Oxide/soluble guanylyl cyclase/cGMP/cGMP-activated protein kinase. NEC, therefore, demonstrates spasmolytic activity when presenting tracheal relaxation compared to CCh and KCl contracturants.
•Nanostructured carrier systems improve the water solubility for that monoterpenes.•Nanoemulsion loaded with camphor (NEC) allows the evaluation mechanism of action of insoluble compounds in in vitro studies.•Camphor has a relaxing effect on rat trachea.•The mechanism of action of camphor involves multiple cell signaling pathways and remains unknown.
ABSTRACT The Andromeda Galaxy recurrent nova M31N 2008-12a had been observed in eruption 10 times, including yearly eruptions from 2008 to 2014. With a measured recurrence period of days (we believe ...the true value to be half of this) and a white dwarf very close to the Chandrasekhar limit, M31N 2008-12a has become the leading pre-explosion supernova type Ia progenitor candidate. Following multi-wavelength follow-up observations of the 2013 and 2014 eruptions, we initiated a campaign to ensure early detection of the predicted 2015 eruption, which triggered ambitious ground- and space-based follow-up programs. In this paper we present the 2015 detection, visible to near-infrared photometry and visible spectroscopy, and ultraviolet and X-ray observations from the Swift observatory. The LCOGT 2 m (Hawaii) discovered the 2015 eruption, estimated to have commenced at August 28.28 0.12 UT. The 2013-2015 eruptions are remarkably similar at all wavelengths. New early spectroscopic observations reveal short-lived emission from material with velocities ∼13,000 km s−1, possibly collimated outflows. Photometric and spectroscopic observations of the eruption provide strong evidence supporting a red giant donor. An apparently stochastic variability during the early supersoft X-ray phase was comparable in amplitude and duration to past eruptions, but the 2013 and 2015 eruptions show evidence of a brief flux dip during this phase. The multi-eruption Swift/XRT spectra show tentative evidence of high-ionization emission lines above a high-temperature continuum. Following Henze et al. (2015a), the updated recurrence period based on all known eruptions is days, and we expect the next eruption of M31N 2008-12a to occur around 2016 mid-September.
The Carrington event is considered to be one of the most extreme space weather events in observational history within a series of magnetic storms caused by extreme interplanetary coronal mass ...ejections from a large and complex active region that emerged on the solar disk. In this article, we study the temporal and spatial evolutions of the source sunspot active region and visual aurorae and compare this storm with other extreme space weather events on the basis of their auroral spatial evolution. Sunspot drawings by Schwabe, Secchi, and Carrington describe the position and morphology of the source active region at that time. Visual auroral reports from the Russian Empire, Iberia, Ireland, Oceania, and Japan fill the spatial gap of auroral visibility and revise the time series of auroral visibility in middle to low magnetic latitudes. The reconstructed time series is compared with magnetic measurements and shows the correspondence between low‐latitude to mid‐latitude aurorae and the phase of magnetic storms. The spatial evolution of the auroral oval is compared with those of other extreme space weather events in 1872, 1909, 1921, and 1989 as well as their storm intensity and contextualizes the Carrington event, as one of the most extreme space weather events, but likely not unique.
Plain Language Summary
The Carrington event is considered to be one of the most extreme space weather events in observational history. In this article, we have studied the temporal and spatial evolutions of the source active region and visual low‐latitude aurorae. We have also compared this storm with other extreme space weather events on the basis of the spatial evolution. We have compared the available sunspot drawings to reconstruct the morphology and evolution of sunspot groups at that time. We have surveyed visual auroral reports in the Russian Empire, Ireland, Iberian Peninsula, Oceania, and Japan and fill the spatial gap of auroral visibility and revised its time series. We have compared this time series with magnetic measurements and shown the correspondence between low‐latitude to midlatitude aurorae and the phase of magnetic storms. We have compared the spatial evolution of the auroral oval with those of other extreme space weather events in 1872, 1909, 1921, and 1989 as well as their storm intensity and concluded that the Carrington event is one of the most extreme space weather events but is likely not unique.
Key Points
Original sunspot drawings during the 1859 storms are revealed and analyzed
New auroral reports from Eurasia and Oceania fill the spatial and temporal gaps of the auroral visibility during the 1859 storms
The 1859 storms are compared and contextualized with the other extreme space weather events
Constitutional genomic imbalances are known to cause malformations, disabilities, neurodevelopmental delay, and dysmorphia and can lead to dysfunctions in the cell cycle. In extremely rare genetic ...conditions such as small supernumerary marker chromosomes (sSMC), it is important to understand the cellular consequences of this extra marker, as well the factors that contribute to their maintenance or elimination through successive cell cycles and phenotypic impact. The study of chromosomal mosaicism provides a natural model to characterize the effect of aneuploidy on genome stability and compare cells with the same genetic background and environment exposure, but differing in the presence of sSMC. Here, we report the functional characterization of different cell lines from two familial patients with mosaic sSMC derived from chromosome 12. We performed studies of proliferation dynamics, stability, and variability of these cells using fluorescent in situ hybridization (FISH), sister chromatid exchanges (SCE), and conventional staining. We also quantified the telomere-related genomic instability of sSMC cells using 3D telomeric profile analysis by quantitative-FISH. sSMC cells exhibited differences in the cell cycle dynamics compared to normal cells. First, the sSMC cells exhibited lower proliferation index and higher frequency of SCE than normal cells, associated with a higher level of chromosomal instability. Second, sSMC cells exhibited more telomeric-related genomic instability. Lastly, the differences of sSMC cells distribution among tissues could explain different phenotypic repercussions observed in patients. These results will help in our understanding of the sSMC stability, maintenance during cell cycle, and the cell cycle variables involved in the different phenotypic manifestations. Key words: Small supernumerary marker chromosomes; Chromosomal instability; Molecular cytogenetics; Genotypephenotype correlation; Telomeres
Rheumatic heart disease remains an important preventable cause of cardiovascular death and disability, particularly in low-income and middle-income countries. We estimated global, regional, and ...national trends in the prevalence of and mortality due to rheumatic heart disease as part of the 2015 Global Burden of Disease study.
We systematically reviewed data on fatal and nonfatal rheumatic heart disease for the period from 1990 through 2015. Two Global Burden of Disease analytic tools, the Cause of Death Ensemble model and DisMod-MR 2.1, were used to produce estimates of mortality and prevalence, including estimates of uncertainty.
We estimated that there were 319,400 (95% uncertainty interval, 297,300 to 337,300) deaths due to rheumatic heart disease in 2015. Global age-standardized mortality due to rheumatic heart disease decreased by 47.8% (95% uncertainty interval, 44.7 to 50.9) from 1990 to 2015, but large differences were observed across regions. In 2015, the highest age-standardized mortality due to and prevalence of rheumatic heart disease were observed in Oceania, South Asia, and central sub-Saharan Africa. We estimated that in 2015 there were 33.4 million (95% uncertainty interval, 29.7 million to 43.1 million) cases of rheumatic heart disease and 10.5 million (95% uncertainty interval, 9.6 million to 11.5 million) disability-adjusted life-years due to rheumatic heart disease globally.
We estimated the global disease prevalence of and mortality due to rheumatic heart disease over a 25-year period. The health-related burden of rheumatic heart disease has declined worldwide, but high rates of disease persist in some of the poorest regions in the world. (Funded by the Bill and Melinda Gates Foundation and the Medtronic Foundation.).
The long-range and short-range WindScanner systems (LRWS and SRWS), multi-Doppler lidar instruments, when combined together can map the turbulent flow around a wind turbine and at the same time ...measure mean flow conditions over an entire region such as a wind farm. As the WindScanner technology is novel, performing field campaigns with the WindScanner systems requires a methodology that will maximize the benefits of conducting WindScanner-based experiments. Such a methodology, made up of 10 steps, is presented and discussed through its application in a pilot experiment that took place in a complex and forested site in Portugal, where for the first time the two WindScanner systems operated simultaneously. Overall, this resulted in a detailed site selection criteria, a well-thought-out experiment layout, novel flow mapping methods and high-quality flow observations, all of which are presented in this paper.
Excitotoxicity is a phenomenon that describes the toxic actions of excitatory neurotransmitters, primarily glutamate, where the exacerbated or prolonged activation of glutamate receptors starts a ...cascade of neurotoxicity that ultimately leads to the loss of neuronal function and cell death. In this process, the shift between normal physiological function and excitotoxicity is largely controlled by astrocytes since they can control the levels of glutamate on the synaptic cleft. This control is achieved through glutamate clearance from the synaptic cleft and its underlying recycling through the glutamate-glutamine cycle. The molecular mechanism that triggers excitotoxicity involves alterations in glutamate and calcium metabolism, dysfunction of glutamate transporters, and malfunction of glutamate receptors, particularly N-methyl-D-aspartic acid receptors (NMDAR). On the other hand, excitotoxicity can be regarded as a consequence of other cellular phenomena, such as mitochondrial dysfunction, physical neuronal damage, and oxidative stress. Regardless, it is known that the excessive activation of NMDAR results in the sustained influx of calcium into neurons and leads to several deleterious consequences, including mitochondrial dysfunction, reactive oxygen species (ROS) overproduction, impairment of calcium buffering, the release of pro-apoptotic factors, among others, that inevitably contribute to neuronal loss. A large body of evidence implicates NMDAR-mediated excitotoxicity as a central mechanism in the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and epilepsy. In this review article, we explore different causes and consequences of excitotoxicity, discuss the involvement of NMDAR-mediated excitotoxicity and its downstream effects on several neurodegenerative disorders, and identify possible strategies to study new aspects of these diseases that may lead to the discovery of new therapeutic approaches. With the understanding that excitotoxicity is a common denominator in neurodegenerative diseases and other disorders, a new perspective on therapy can be considered, where the targets are not specific symptoms, but the underlying cellular phenomena of the disease.
Seaweeds, such as Laminaria digitata, are a sustainable alternative to conventional feedstuffs for weaned piglet diets, improving their health and mitigating environmental impacts. L. digitata has a ...complex cell wall that can be difficult for monogastrics to digest. However, carbohydrate-active enzymes (CAZymes) such as Rovabio
Excel AP and alginate lyase can help break down these polysaccharides and render intracellular nutrients more accessible. This study aimed to evaluate the impact of 10% L. digitata feed inclusion and CAZyme supplementation on piglet blood cells, serum metabolites, liver lipid and mineral profiles. Forty weaned piglets were randomly assigned to one of four diets (n = 10 each): a control diet, 10% L. digitata (LA), 10% L. digitata + 0.005% Rovabio
Excel AP (LAR), and 10% L. digitata + 0.01% alginate lyase (LAL). After two weeks of trial, animals were slaughtered and liver and blood serum samples taken for analysis. The results showed that the LA and LAL diets increased blood lymphocytes, IgG and IgM, and decreased serum lipids, improving both cellular and humoral immune response and cardiovascular health. Dietary CAZymes reversed the anti-inflammatory and hematopoietic effects. Additionally, cortisol levels were reduced with seaweed inclusion compared to the control diet (P < 0.001). In the liver, total n-3 PUFA and n-6/n-3 ratio were increased and decreased, respectively, due to eicosapentaenoic acid and α-linolenic acid accumulation (P < 0.001). However, total liver mineral content was incorporated to a lesser extent with the combined seaweed and enzyme diets (P < 0.001), potentially indicating a negative effect on mineral bioavailability. Overall, results suggest that a 10% L. digitata inclusion can effectively improve piglet health by reducing stress during weaning, without the need for dietary CAZymes.
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