365 research outputs found
In vitro Evaluation of a hydroxypropyl cellulose gel system for transdermal delivery of timolol
Protein folding kinetics: barrier effects in chemical and thermal denaturation experiments
10 pages, 5 figures.-- PMID: 17419630 [PubMed].-- PMCID: PMC2527040.-- Author manuscript available in PMC: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17419630Printed version published on May 2, 2007.Recent experimental work on fast protein folding brings about an intriguing paradox. Microsecond-folding proteins are supposed to fold near or at the folding speed limit (downhill folding), but yet their folding behavior seems to comply with classical two-state analyses, which imply the crossing of high free energy barriers. However, close inspection of chemical and thermal denaturation kinetic experiments in fast-folding proteins reveals systematic deviations from two-state behavior. Using a simple one-dimensional free energy surface approach we find that such deviations are indeed diagnostic of marginal folding barriers. Furthermore, the quantitative analysis of available fast-kinetic data indicates that many microsecond-folding proteins fold downhill in native conditions. All of these proteins are then promising candidates for an atom-by-atom analysis of protein folding using nuclear magnetic resonance. We also find that the diffusion coefficient for protein folding is strongly temperature dependent, corresponding to an activation energy of ~1 kJ·mol-1 per protein residue. As a consequence, the folding speed limit at room temperature is about an order of magnitude slower than the ~ 1 μs estimates from high-temperature T-jump experiments. Our analysis is quantitatively consistent with the available thermodynamic and kinetic data on slow two-state folding proteins and provides a straightforward explanation for the apparent fast-folding paradox.This research has been supported by NIH grant GM066800-1 and NSF grant MCB-0317294.Peer reviewe
Detection and quantification of classic and emerging viruses by skimmed-milk flocculation and PCR in river water from two geographical areas
Molecular techniques and virus concentration methods have shown that previously unknown viruses are shed by humans and animals, and may be transmitted by sewage-contaminated water. In the present study, river water from urban areas in Barcelona, Spain and Rio de Janeiro, Brazil, were analyzed to evaluate the dissemination of human viruses, while simultaneously optimizing and validating a low-cost concentration method for virus quantification in fresh water. The following three viral groups were analyzed. (i) Recently described viruses: klassevirus (KV), asfarvirus-like virus (ASFLV), and the polyomaviruses Merkel cell, KI and WU (MCPyV/KIPyV/WUPyV). (ii) Gastroenteritis agents: noroviruses (NoV) and rotaviruses (RV). (iii) Human fecal viral indicators in water: human adenoviruses (HAdV) and JC polyomaviruses (JCPyV). Virus detection was based on nested and quantitative PCR assays. Nested PCR assays were developed for KV and ASFLV. The method applied for virus concentration in water samples was a one-step procedure based on a skimmed milk flocculation procedure described previously for seawater. Using spiked river water samples, inter- and intra-laboratory assays showed a viral recovery rate of about 50% for HAdV, JCPyV, NoV and RV with a coefficient of variation ≤ 50%. HAdV and JCPyV were detected in 100% of the river samples from Barcelona and Rio de Janeiro. Moreover, NoV GGII was detected in 100% and MCPyV in 50% of the samples from Barcelona, whereas none of the other viruses analyzed were detected. NoV GGII was detected in 33%, KV in 33%, ASFLV in 17% and MCPyV in 50% of the samples from Rio de Janeiro, whereas KIPyV and WUPyV were not detected. RV were only tested for in Rio de Janeiro and resulted positive in 67% of the samples. The procedure applied here to river water represents a useful, straightforward and cost-effective method that could be applied in routine water quality testing. The results of the assays expand our understanding of the global distribution of the viral pathogens studied here and their persistence in the environment. Fil: Calgua, B.. Universidad de Barcelona; España;Fil: Fumian, T.. Ministerio de Salud de Brasil. Fundacion Oswaldo Cruz; Brasil;Fil: Rusinol, M.. Universidad de Barcelona; España;Fil: Rodríguez Manzano, J.. Universidad de Barcelona; España;Fil: Mbayed, Viviana Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Bofill Mas, S.. Universidad de Barcelona; España;Fil: Miagostovich, M.. Ministerio de Salud de Brasil. Fundacion Oswaldo Cruz; Brasil;Fil: Girones, R.. Universidad de Barcelona; España
Accumulation of Flavonols over Hydroxycinnamic Acids Favors Oxidative Damage Protection under Abiotic Stress
Efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Although multiple pathways, enzymes, and antioxidants are present in plants, their exact roles during different stress responses remain unclear. Here, we report on the characterization of the different antioxidant mechanisms of tomato plants subjected to heat stress, salinity stress, or a combination of both stresses. All the treatments applied induced an increase of oxidative stress, with the salinity treatment being the most aggressive, resulting in plants with the lowest biomass, and the highest levels of H2O2 accumulation, lipid peroxidation, and protein oxidation. However, the results obtained from the transcript expression study and enzymatic activities related to the ascorbate-glutathione pathway did not fully explain the differences in the oxidative damage observed between salinity and the combination of salinity and heat. An exhaustive metabolomics study revealed the differential accumulation of phenolic compounds depending on the type of abiotic stress applied. An analysis at gene and enzyme levels of the phenylpropanoid metabolism concluded that under conditions where flavonols accumulated to a greater degree as compared to hydroxycinnamic acids, the oxidative damage was lower, highlighting the importance of flavonols as powerful antioxidants, and their role in abiotic stress tolerance.This work was supported by the Ministry of Economy and Competitiveness from Spain (GrantNo. AGL2015-66033-R), and Seneca Foundation from Region of Murcia, Spain (Grant no.15288/ PI/10).Peer reviewedPeer Reviewe
Klassevirus 1, a previously undescribed member of the family Picornaviridae, is globally widespread
Background Diarrhea is the third leading infectious cause of death worldwide and is estimated to be responsible for approximately 2 million deaths a year. While many infectious causes of diarrhea have been established, approximately 40% of all diarrhea cases are of unknown etiology. In an effort to identify novel viruses that may be causal agents of diarrhea, we used high throughput mass sequencing to analyze stool samples collected from patients with acute diarrhea. Results Sequences with limited similarity to known picornaviruses were detected in a stool sample collected in Australia from a child with acute diarrhea. Using a combination of mass sequencing, RT-PCR, 5' RACE and 3' RACE, a 6383 bp fragment of the viral genome was sequenced. Phylogenetic analysis demonstrated that this virus was highly divergent from, but most closely related to, members of the genus Kobuvirus. We have tentatively named this novel virus klassevirus 1. We also detected klassevirus 1 by RT-PCR in a diarrhea specimen collected from a patient in St. Louis, United States as well as in untreated sewage collected in Barcelona, Spain. Conclusion Klassevirus 1 is a previously undescribed picornavirus that is globally widespread and present on at least three continents. Further investigations to determine whether klassevirus 1 is a human pathogen are needed
Revealing patterns of local species richness along environmental gradients with a novel network tool
How species richness relates to environmental gradients at large extents is commonly investigatedaggregating local site data to coarser grains. However, such relationships often change with the grainof analysis, potentially hiding the local signal. Here we show that a novel network technique, the"method of reflections", could unveil the relationships between species richness and climate withoutsuch drawbacks. We introduced a new index related to potential species richness, which revealedlarge scale patterns by including at the local community level information about species distributionthroughout the dataset (i.e., the network). The method effectively removed noise, identifying howfar site richness was from potential. When applying it to study woody species richness patterns inSpain, we observed that annual precipitation and mean annual temperature explained large parts ofthe variance of the newly defined species richness, highlighting that, at the local scale, communitiesin drier and warmer areas were potentially the species richest. Our method went far beyond whatgeographical upscaling of the data could unfold, and the insights obtained strongly suggested that itis a powerful instrument to detect key factors underlying species richness patterns, and that it couldhave numerous applications in ecology and other fields.Comunidad de MadridMinisterio de Economía y Competitivida
Raw Sewage Harbors Diverse Viral Populations
At this time, about 3,000 different viruses are recognized, but metagenomic studies suggest that these viruses are a small fraction of the viruses that exist in nature. We have explored viral diversity by deep sequencing nucleic acids obtained from virion populations enriched from raw sewage. We identified 234 known viruses, including 17 that infect humans. Plant, insect, and algal viruses as well as bacteriophages were also present. These viruses represented 26 taxonomic families and included viruses with single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), positive-sense ssRNA [ssRNA(+)], and dsRNA genomes. Novel viruses that could be placed in specific taxa represented 51 different families, making untreated wastewater the most diverse viral metagenome (genetic material recovered directly from environmental samples) examined thus far. However, the vast majority of sequence reads bore little or no sequence relation to known viruses and thus could not be placed into specific taxa. These results show that the vast majority of the viruses on Earth have not yet been characterized. Untreated wastewater provides a rich matrix for identifying novel viruses and for studying virus diversity
The Miniaturized Moessbauer Spectrometers MIMOS II on MER: Four Years of Operation - A Summary
The two Miniaturized Moessbauer Spectrometers (MIMOS II) on board the two Mars Exploration Rovers Spirit and Opportunity have now been collecting important scientific data for more than four years. The spectrometers provide information about Fe-bearing mineral phases and determine Fe oxidation states. The total amount of targets analized exceeds 600, the total integration time exceeds 260 days for both rovers. Since landing, more than five half-lives of the Co-57 MB sources have past (intensity at the time of landing approx. 150 mCi). Current integration times are about 50 hours in order to achieve reasonable statistics as opposed to 8 hours at the beginning of the mission. In total, 13 different mineral phases were detected: Olivine, pyroxene, hematite, magnetite and nanophase ferric oxide were detected at both landing sites. At Gusev, ilmenite, goethite, a ferric sulfate phase and a yet unassigned phase (in the rock Fuzzy Smith) were detected. At Meridiani, jarosite, metallic iron in meteoritic samples (kamacite), troilite, and an unassigned ferric phase were detected. Jarosite and goethite are of special interest, as these minerals are indicators for water activity. In this abstract, an overview of Moessbauer results will be given, with a focus on data obtained since the last martian winter. The MER mission has proven that Moessbauer spectroscopy is a valuable tool for the in situ exploration of extraterrestrial bodies and for the study of Febearing samples. The experience gained through the MER mission makes MIMOS II a obvious choice for future missions to Mars and other targets. Currently, MIMOS II is on the scientific payload of two approved future missions: Phobos Grunt (Russian Space Agency; 2009) and ExoMars (European Space Agency; 2013)
The PAU survey: classifying low-z SEDs using Machine Learning clustering
This is a pre-copyedited, author-produced PDF of an article accepted for publication in Monthly Notices of the Royal Astronomical Society following peer review. The version of record Monthly Notices of the Royal Astronomical Society 524.3 (2023): 3569-3581
is available online at: https://academic.oup.com/mnras/article-abstract/524/3/3569/7225529?redirectedFrom=fulltextWe present an application of unsupervised Machine Learning clustering to the PAU survey of galaxy spectral energy distribution (SED) within the COSMOS field. The clustering algorithm is implemented and optimized to get the relevant groups in the data SEDs. We find 12 groups from a total number of 5234 targets in the survey at 0.01 < z < 0.28. Among the groups, 3545 galaxies (68 per cent) show emission lines in the SEDs. These groups also include 1689 old galaxies with no active star formation. We have fitted the SED to every single galaxy in each group with CIGALE. The mass, age, and specific star formation rates (sSFR) of the galaxies range from 0.15 < age/Gyr <11; 6 < log (M/M⊙) <11.26, and -14.67 < log (sSFR/yr-1) <-8. The groups are well-defined in their properties with galaxies having clear emission lines also having lower mass, are younger and have higher sSFR than those with elliptical like patterns. The characteristic values of galaxies showing clear emission lines are in agreement with the literature for starburst galaxies in COSMOS and GOODS-N fields at low redshift. The star-forming main sequence, sSFR versus stellar mass and UVJ diagram show clearly that different groups fall into different regions with some overlap among groups. Our main result is that the joint of low- resolution (R ∼50) photometric spectra provided by the PAU survey together with the unsupervised classification provides an excellent way to classify galaxies. Moreover, it helps to find and extend the analysis of extreme ELGs to lower masses and lower SFRs in the local UniverseThis work has been supported by the Ministry of Science and Innovation of Spain, project PID2019-107408GB-C43 (ESTALLIDOS), and the Government of the Canary Islands through EU FEDER funding, projects PID2020010050 and PID2021010077. This article is based on observations made in the Observatorios de Canarias of the Instituto de Astrofísica de Canarias (IAC) with the WHT operated on the island of La Palma by the Isaac Newton Group of Telescopes (ING) in the Observatorio del Roque de los Muchachos. The PAU Survey is partially supported by MINECO under grants CSD2007-00060, AYA2015-71825, ESP2017-89838, PGC2018-094773, PGC2018-102021, PID2019-111317GB, SEV-2016-0588, SEV-2016-0597, MDM-2015-0509 and Juan de la Cierva fellowship and LACEGAL and EWC Marie Sklodowska-Curie grant No 734374 and no.776247 with ERDF funds from the EU Horizon 2020 Programme, some of which include ERDF funds from the European Union. IEEC and IFAE are partially funded by the CERCA and Beatriu de Pinos program of the Generalitat de Catalunya. Funding for PAUS has also been provided by Durham Univer sity (via the ERC StG DEGAS-259586), ETH Zurich, Leiden University (via ERC StG ADULT-279396 and Netherlands Organisation for Scientific Research (NWO) Vici grant 639.043.512), University College London and from the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 776247 EWC. The PAU data center is hosted by the Port d’Información Científica (PIC), maintained through a collaboration of CIEMAT and IFAE, with additional support from Universitat Autónoma de Barcelona and ERDF. We acknowledge the PIC services department team for their support and fruitful discussion
Characterization of the selectivity of microsieves using a cross-flow microfiltration system
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