419 research outputs found
How to avoid potential pitfalls in recurrence plot based data analysis
Recurrence plots and recurrence quantification analysis have become popular
in the last two decades. Recurrence based methods have on the one hand a deep
foundation in the theory of dynamical systems and are on the other hand
powerful tools for the investigation of a variety of problems. The increasing
interest encompasses the growing risk of misuse and uncritical application of
these methods. Therefore, we point out potential problems and pitfalls related
to different aspects of the application of recurrence plots and recurrence
quantification analysis
Mitochondrial DNA Variability among Six South American Amerindian Villages from the Pano Linguistic Group
Metabolomics methods for the synthetic biology of secondary metabolism
Many microbial secondary metabolites are of high biotechnological value for medicine, agriculture, and the food industry. Bacterial genome mining has revealed numerous novel secondary metabolite biosynthetic gene clusters, which encode the potential to synthesize a large diversity of compounds that have never been observed before. The stimulation or “awakening” of this cryptic microbial secondary metabolism has naturally attracted the attention of synthetic microbiologists, who exploit recent advances in DNA sequencing and synthesis to achieve unprecedented control over metabolic pathways. One of the indispensable tools in the synthetic biology toolbox is metabolomics, the global quantification of small biomolecules. This review illustrates the pivotal role of metabolomics for the synthetic microbiology of secondary metabolism, including its crucial role in novel compound discovery in microbes, the examination of side products of engineered metabolic pathways, as well as the identification of major bottlenecks for the overproduction of compounds of interest, especially in combination with metabolic modeling. We conclude by highlighting remaining challenges and recent technological advances that will drive metabolomics towards fulfilling its potential as a cornerstone technology of synthetic microbiology
Mitochondrial echoes of first settlement and genetic continuity in El Salvador
Background: From Paleo-Indian times to recent historical episodes, the Mesoamerican isthmus played an important role in the distribution and patterns of variability all around the double American continent. However, the amount of genetic information currently available on Central American continental populations is very scarce. In order to shed light on the role of Mesoamerica in the peopling of the New World, the present study focuses on the analysis of the mtDNA variation in a population sample from El Salvador.
Methodology/Principal Findings: We have carried out DNA sequencing of the entire control region of the mitochondrial DNA (mtDNA) genome in 90 individuals from El Salvador. We have also compiled more than 3,985 control region profiles from the public domain and the literature in order to carry out inter-population comparisons. The results reveal a predominant Native American component in this region: by far, the most prevalent mtDNA haplogroup in this country (at ~90%) is A2, in contrast with other North, Meso- and South American populations. Haplogroup A2 shows a star-like phylogeny and is very diverse with a substantial proportion of mtDNAs (45%; sequence range 16090–16365) still unobserved in other American populations. Two different Bayesian approaches used to estimate admixture proportions in El Salvador shows that the majority of the mtDNAs observed come from North America. A preliminary founder analysis indicates that the settlement of El Salvador occurred about 13,400±5,200 Y.B.P.. The founder age of A2 in El Salvador is close to the overall age of A2 in America, which suggests that the colonization of this region occurred within a few thousand years of the initial expansion into the Americas.
Conclusions/Significance: As a whole, the results are compatible with the hypothesis that today's A2 variability in El Salvador represents to a large extent the indigenous component of the region. Concordant with this hypothesis is also the observation of a very limited contribution from European and African women (~5%). This implies that the Atlantic slave trade had a very small demographic impact in El Salvador in contrast to its transformation of the gene pool in neighbouring populations from the Caribbean facade
Enhanced acylcarnitine annotation in high-resolution mass spectrometry data:Fragmentation analysis for the classification and annotation of acylcarnitines
Metabolite annotation and identification are primary challenges in untargeted metabolomics experiments. Rigorous workflows for reliable annotation of mass features with chemical structures or compound classes are needed to enhance the power of untargeted mass spectrometry. High-resolution mass spectrometry considerably improves the confidence in assigning elemental formulas to mass features in comparison to nominal mass spectrometry, and embedding of fragmentation methods enables more reliable metabolite annotations and facilitates metabolite classification. However, the analysis of mass fragmentation spectra can be a time-consuming step and requires expert knowledge.<p></p>
This study demonstrates how characteristic fragmentations, specific to compound classes, can be used to systematically analyze their presence in complex biological extracts like urine that underwent untargeted mass spectrometry combined with data dependent or targeted fragmentation. Human urine extracts were analyzed using normal phase liquid chromatography (HILIC) coupled to an Ion Trap-Orbitrap hybrid instrument. Subsequently, mass chromatograms and CID and HCD fragments were annotated using the freely available MAGMa software.<p></p>
Acylcarnitines play a central role in energy metabolism by transporting fatty acids into the mitochondrial matrix. By filtering on a combination of a mass fragment and neutral loss designed based on the MAGMa fragment annotations, we were able to classify and annotate 50 acylcarnitines in human urine extracts, based on high-resolution mass spectrometry HCD fragmentation spectra at different energies for all of them. Of these annotated acylcarnitines, 31 are not described in HMDB yet and for only 4 annotated acylcarnitines the fragmentation spectra could be matched to reference spectra. Therefore, we conclude that the use of mass fragmentation filters within the context of untargeted metabolomics experiments is a valuable tool to enhance the annotation of small metabolites.<p></p>
Mitochondrial DNA Evidence for a Diversified Origin of Workers Building Mausoleum for First Emperor of China
Variant studies on ancient DNA have attempted to reveal individual origin. Here, based on cloning sequencing and polymerase chain reaction-restriction fragment length polymorphisms, we analyzed polymorphisms in the first hypervariable region and coding regions of mitochondrial DNA of 19 human bone remains which were excavated from a tomb near the Terra Cotta Warriors and dated some 2,200 years before present. With the aim of shedding light on origins of these samples who were supposed to be workers building the mausoleum for the First Emperor of China, we compared them with 2,164 mtDNA profiles from 32 contemporary Chinese populations at both population and individual levels. Our results showed that mausoleum-building workers may be derived from very diverse sources of origin
Search for astronomical neutrinos from blazar TXS 0506+056 in super-kamiokande
We report a search for astronomical neutrinos in the energy region from several GeV to TeV in the direction of the blazar TXS 0506+056 using the Super-Kamiokande detector following the detection of a 100 TeV neutrinos from the same location by the IceCube collaboration. Using Super-Kamiokande neutrino data across several data samples observed from 1996 April to 2018 February we have searched for both a total excess above known backgrounds across the entire period as well as localized excesses on smaller timescales in that interval. No significant excess nor significant variation in the observed event rate are found in the blazar direction. Upper limits are placed on the electron- and muon-neutrino fluxes at the 90% confidence level as 6.0 × 10−7 and 4.5 × 10−7–9.3 × 10−10 [erg cm−2 s−1], respectively
Upper mantle velocity-temperature conversion and composition determined from seismic refraction and heat flow
International audience[1] We compile upper mantle P n velocities from seismic refraction/wide-angle reflection surveys in the southern Superior Province of the Canadian Shield and compare them with temperatures at the Moho deduced from heat flow data. Calculated Moho temperatures and P n velocities correlate well, showing that in this area, P n depends primarily on temperature. The obtained values of @V(P n)/@T depend weakly on the assumed value of Moho heat flow and are on the order of À6.0 Â 10 À4 ± 10% km s À1 K À1 , within the range of temperature derivatives obtained in laboratory studies of ultramafic rocks. Comparison between observed P n velocities and predicted values for several mineralogical models at Moho temperatures allows constraints on both the Moho heat flow and the shallow mantle composition. For all Moho heat flows, undepleted (clinopyroxene-rich) mantle compositions do not allow a good fit to the data. For depleted mantle compositions, temperatures consistent with the observed P n velocities correspond to values of Moho heat flow larger than 12 mW m À2. For our preferred Moho heat flow of 15 mW m À2 , the best fit mantle composition is slightly less depleted than models for average Archean subcontinental lithospheric mantle. This may be due to rejuvenation by melt-related metasomatism during the Keweenawan rifting event. The similarity in P n À T conversion factors estimated from this empirical large-scale geophysical study and those from laboratory data provides confidence in the absolute temperature values deduced from heat flow measurements and seismic studies. Citation: Perry, H. K. C., C. Jaupart, J.-C. Mareschal, and N. M. Shapiro (2006), Upper mantle velocity-temperature conversion and composition determined from seismic refraction and heat flow
Metabolite profiling of Dioscorea (yam) species reveals underutilised biodiversity and renewable sources for high-value compounds
Yams (Dioscorea spp.) are a multispecies crop with production in over 50 countries generating ~50 MT of edible tubers annually. The long-term storage potential of these tubers is vital for food security in developing countries. Furthermore, many species are important sources of pharmaceutical precursors. Despite these attributes as staple food crops and sources of high-value chemicals, Dioscorea spp. remain largely neglected in comparison to other staple tuber crops of tropical agricultural systems such as cassava (Manihot esculenta) and sweet potato (Ipomoea batatas). To date, studies have focussed on the tubers or rhizomes of Dioscorea, neglecting the foliage as waste. In the present study metabolite profiling procedures, using GC-MS approaches, have been established to assess biochemical diversity across species. The robustness of the procedures was shown using material from the phylogenetic clades. The resultant data allowed separation of the genotypes into clades, species and morphological traits with a putative geographical origin. Additionally, we show the potential of foliage material as a renewable source of high-value compounds
Much Ado About the TPP’s Effect on Pharmaceuticals
Ocular antigens are sequestered behind the blood-retina barrier and the ocular environment protects ocular tissues from autoimmune attack. The signals required to activate autoreactive T cells and allow them to cause disease in the eye remain in part unclear. In particular, the consequences of peripheral presentation of ocular antigens are not fully understood. We examined peripheral expression and presentation of ocular neo-self-antigen in transgenic mice expressing hen egg lysozyme (HEL) under a retina-specific promoter. High levels of HEL were expressed in the eye compared to low expression throughout the lymphoid system. Adoptively transferred naïve HEL-specific CD4+ T cells proliferated in the eye draining lymph nodes, but did not induce uveitis. By contrast, systemic infection with a murine cytomegalovirus (MCMV) engineered to express HEL induced extensive proliferation of transferred naïve CD4+ T cells, and significant uveoretinitis. In this model, wild-type MCMV, lacking HEL, did not induce overt uveitis, suggesting that disease is mediated by antigen-specific peripherally activated CD4+ T cells that infiltrate the retina. Our results demonstrate that retinal antigen is presented to T cells in the periphery under physiological conditions. However, when the same antigen is presented during viral infection, antigen-specific T cells access the retina and autoimmune uveitis ensues
- …