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

Neonatal umbilical cord blood cardiac troponin as reflecting fetal growth, age and well being

Objectives: It has been proposed that an elevated concentration of cardiac troponin in umbilical cord blood may function as a surrogate marker of ischemic damage sustained in utero and/or during labour and delivery. The objective of this study is to document the umbilical cord blood concentrations of troponins I (cTnI) and T (cTnT) using high sensitivity assays and correlate these with maternal and fetal clinical history.Methods: Umbilical cord blood was collected immediately following delivery from 416 babies, including 12 sets of twins. Clinical history was obtained from clinical notes. Ethics permission was obtained from ACT Health Human Research and Ethics Committee for the study and consent was obtained from mothers for their participation. Cardiac troponins were assayed using hs- cTnI on Abbott Architect (LoD 1.0 ng/L) and hs-cTnT on Roche E4111 (LoD 5.0 ng/L). Data are expressed as median and 25th and 75th percentiles.Results: Umbilical cord blood consistently has higher median values of cTnT than cTnI such that the median ratios are 6.8 and 5.4 at <32 week gestation and 41 week babies respectively compared with T:I of 0.8 in adults. Babies of early gestation have higher concentrations of cTnT and cTnI as do babies with APGAR scores ≤4 at 1 min. Median cTn concentrations show a 50% decrease between babies born< 32 weeks and those at full term.Relationship of birth weight and umbilical cord cardiac troponin concentrations. Low Birth Weight babies have~50% higher cTn concentrationsConclusions: These findings are consistent with a differential expression of cTnT and cTnI in utero with potential contributions from growth and re-modelling of the heart in addition to “ectopic” production in less differentiated non-cardiac muscle. The effect of intermittent ischemia which occurs as part of normal labour and delivery may superimpose on this increments

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

Macro and micromechanics analysis of short fiber composites stiffness: The case of old newspaper fibers-polypropylene composites

Stiffness is one of the most relevant characteristics of composite materials. Natural wood fibers have demonstrated their ability to increase the Young's moduli of composite materials, and old newspapers are a potential source of reinforcing fibers for composite materials. There are some micromechanic models to predict the Young's modulus of composite materials, and one of the input data is the intrinsic modulus of their fibers. This intrinsic modulus is a value which is difficult or impossible to measure in the case of wood fibers, due to their measures. This paper evaluates the stiffening abilities of old newspaper fibers and the possibility to back calculate the value of the intrinsic Young's Modulus by means of micromechanic models. Different percentages of old newspaper fibers were compounded with polypropylene (PP). Micromechanics of the fibers were obtained using Hirsch model, Cox-Krenchel's model, Tsai-Pagano model and Halpin-Tsai equations. The most important results were the average intrinsic Young's modulus of the fibers, the mean orientation angle and the mean modulus efficiency factor.Serrano, A.; Espinach, FX.; Tresserras, J.; Rey Tormos, RMD.; Pellicer, N.; Mutje Pujol, P. (2014). Macro and micromechanics analysis of short fiber composites stiffness: The case of old newspaper fibers-polypropylene composites. Materials and Design. 55:319-324. doi:10.1016/j.matdes.2013.10.011S3193245

The Self Model and the Conception of Biological Identity in Immunology

The self/non-self model, first proposed by F.M. Burnet, has dominated immunology for sixty years now. According to this model, any foreign element will trigger an immune reaction in an organism, whereas endogenous elements will not, in normal circumstances, induce an immune reaction. In this paper we show that the self/non-self model is no longer an appropriate explanation of experimental data in immunology, and that this inadequacy may be rooted in an excessively strong metaphysical conception of biological identity. We suggest that another hypothesis, one based on the notion of continuity, gives a better account of immune phenomena. Finally, we underscore the mapping between this metaphysical deflation from self to continuity in immunology and the philosophical debate between substantialism and empiricism about identity