Anaplastic gliomas, the most common and malignant of primary brain tumors, frequently contain activating mutations and amplifications in promigratory signal transduction pathways. However, targeting ...these pathways with individual signal transduction inhibitors does not appreciably reduce tumor invasion, because these pathways are redundant; blockade of any one pathway can be overcome by stimulation of another. This implies that a more effective approach would be to target a component at which these pathways converge. In this study, we have investigated whether the molecular motor myosin II represents such a target by examining glioma invasion in a series of increasingly complex models that are sensitive to platelet-derived growth factor, epidermal growth factor, or both. Our results lead to two conclusions. First, malignant glioma cells are stimulated to invade brain through the activation of multiple signaling cascades not accounted for in simple in vitro assays. Second, even though there is a high degree of redundancy in promigratory signaling cascades in gliomas, blocking tumor invasion by directly targeting myosin II remains effective. Our results thus support our hypothesis that myosin II represents a point of convergence for signal transduction pathways that drive glioma invasion and that its inhibition cannot be overcome by other motility mechanisms.
•The effect of UHPH on the bioactive compounds of soymilk was studied.•Phytosterol and isoflavone extractability increased with the UHPH treatments.•Tocopherols were affected by the effect of UHPH ...treatment.•Polyamines were stable with the combinations of pressure and temperature applied.
Ultra high pressure homogenization (UHPH) is a useful novel technology to obtain safe and high-quality liquid foods. The effect of UHPH at 200 and 300MPa in combination with different inlet temperatures (Tin) (55, 65 and 75°C) on the bioactive compounds of soya milk was studied. Total phytosterols increased with the higher combination of pressure and temperature. The main phytosterol was β-sitosterol, followed by stigmasterol and campesterol. Total tocopherols in UHPH-treated soya milks decreased as the temperature and pressure increased. UHPH treatment also affected the different chemical forms of tocopherols. No biogenic amines were detected in any of the analyzed soya milks. Meanwhile, the polyamines SPD and SPM were found in all soya milks, being stable to the UHPH treatment. Total isoflavones increased with the higher combination of pressure and temperature. No differences in the isoflavone profile were found, with β-glucoside conjugates being the predominant form.
Abstract
Motivation
Combining multiple layers of information underlying biological complexity into a structured framework represent a challenge in systems biology. A key task is the formalization of ...such information in models describing how biological entities interact to mediate the response to external and internal signals. Several databases with signalling information, focus on capturing, organizing and displaying signalling interactions by representing them as binary, causal relationships between biological entities. The curation efforts that build these individual databases demand a concerted effort to ensure interoperability among resources.
Results
Aware of the enormous benefits of standardization efforts in the molecular interaction research field, representatives of the signalling network community agreed to extend the PSI-MI controlled vocabulary to include additional terms representing aspects of causal interactions. Here, we present a common standard for the representation and dissemination of signalling information: the PSI Causal Interaction tabular format (CausalTAB) which is an extension of the existing PSI-MI tab-delimited format, now designated PSI-MITAB 2.8. We define the new term ‘causal interaction’, and related child terms, which are children of the PSI-MI ‘molecular interaction’ term. The new vocabulary terms in this extended PSI-MI format will enable systems biologists to model large-scale signalling networks more precisely and with higher coverage than before.
Availability and implementation
PSI-MITAB 2.8 format and the new reference implementation of PSICQUIC are available online (https://psicquic.github.io/ and https://psicquic.github.io/MITAB28Format.html).
Supplementary information
Supplementary data are available at Bioinformatics online.
Electron scattering and neutrino physics Ankowski, A M; Ashkenazi, A; Bacca, S ...
Journal of physics. G, Nuclear and particle physics,
12/2023, Letnik:
50, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Abstract
A thorough understanding of neutrino–nucleus scattering physics is crucial for the successful execution of the entire US neutrino physics program. Neutrino–nucleus interaction constitutes ...one of the biggest systematic uncertainties in neutrino experiments—both at intermediate energies affecting long-baseline deep underground neutrino experiment, as well as at low energies affecting coherent scattering neutrino program—and could well be the difference between achieving or missing discovery level precision. To this end, electron–nucleus scattering experiments provide vital information to test, assess and validate different nuclear models and event generators intended to test, assess and validate different nuclear models and event generators intended to be used in neutrino experiments. Similarly, for the low-energy neutrino program revolving around the coherent elastic neutrino–nucleus scattering (CEvNS) physics at stopped pion sources, such as at ORNL, the main source of uncertainty in the evaluation of the CEvNS cross section is driven by the underlying nuclear structure, embedded in the weak form factor, of the target nucleus. To this end, parity-violating electron scattering (PVES) experiments, utilizing polarized electron beams, provide vital model-independent information in determining weak form factors. This information is vital in achieving a percent level precision needed to disentangle new physics signals from the standard model expected CEvNS rate. In this white paper, we highlight connections between electron- and neutrino–nucleus scattering physics at energies ranging from 10 s of MeV to a few GeV, review the status of ongoing and planned electron scattering experiments, identify gaps, and lay out a path forward that benefits the neutrino community. We also highlight the systemic challenges with respect to the divide between the nuclear and high-energy physics communities and funding that presents additional hurdles in mobilizing these connections to the benefit of neutrino programs.
► This study validated a UHPLC–UV method for the determination of soymilk isoflavones. ► Chromatographic analysis allowed complete separation of 12 isoflavones in 8min. ► The method requires lower ...amounts of solvents than conventional HPLC approaches.
Ultra high pressure liquid chromatography (UHPLC) has become a widely used technique in separation science as it can shorten analysis time while maintaining resolution and increasing sensitivity. Here we developed a UHPLC method with UV detection for the simultaneous determination of isoflavone aglycones (daidzein, glycitein and genistein), their corresponding glycoside forms (daidzin, glycitin and genistin), and acetyl and malonyl conjugate forms of glycosides (malonyldaidzin, malonylglycitin, malonylgenistin, acetyldaidzin, acetylglycitin, acetylgenistin) in soy milk. The method allowed reliable determinations of 12 isoflavones in less than 8min of chromatographic elution. It provided a satisfactory linearity ranging from 0.1 to 5mg/L, except for daidzin and genistin, for which it ranged from 0.1 to 10mg/L. In addition, it showed acceptable chromatographic sensitivity, with a detection limit lower than 0.05mg/L and a determination limit below 0.2mg/L. The precision, in terms of relative standard deviation, was lower than 5% and the accuracy, as mean recovery, was greater than 95%. Total isoflavone content in commercial soy milk samples (n=8) ranged from 1805.22 to 3195.59mg/kg dw. Genistin and Daidzin were the major isoflavones in all samples. The proportion of aglycones, ß-glucosides, and acetyl and malonyl glucosides differed among the samples. ß-Glucosides were identified as the predominant forms.
A number of different molecular interactions data download formats now exist, designed to allow access to these valuable data by diverse user groups. These formats include the PSI-XML and MITAB ...standard interchange formats developed by Molecular Interaction workgroup of the HUPO-PSI in addition to other, use-specific downloads produced by other resources. The onus is currently on the user to ensure that a piece of software is capable of read/writing all necessary versions of each format. This problem may increase, as data providers strive to meet ever more sophisticated user demands and data types.
A collaboration between EMBL-EBI and the University of Cambridge has produced JAMI, a single library to unify standard molecular interaction data formats such as PSI-MI XML and PSI-MITAB. The JAMI free, open-source library enables the development of molecular interaction computational tools and pipelines without the need to produce different versions of software to read different versions of the data formats.
Software and tools developed on top of the JAMI framework are able to integrate and support both PSI-MI XML and PSI-MITAB. The use of JAMI avoids the requirement to chain conversions between formats in order to reach a desired output format and prevents code and unit test duplication as the code becomes more modular. JAMI's model interfaces are abstracted from the underlying format, hiding the complexity and requirements of each data format from developers using JAMI as a library.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The current coronavirus disease of 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2, has spurred a wave of research of nearly unprecedented ...scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions can provide fine-grained resolution of the mechanisms behind the virus biology and the human organism response. We present a curated dataset of physical molecular interactions focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family that has been manually extracted by International Molecular Exchange (IMEx) Consortium curators. Currently, the dataset comprises over 4400 binarized interactions extracted from 151 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website (https://www.ebi.ac.uk/intact) and will be continuously updated as research on COVID-19 progresses.
Systems biologists study interaction data to understand the behaviour of whole cell systems, and their environment, at a molecular level. In order to effectively achieve this goal, it is critical ...that researchers have high quality interaction datasets available to them, in a standard data format, and also a suite of tools with which to analyse such data and form experimentally testable hypotheses from them. The PSI-MI XML standard interchange format was initially published in 2004, and expanded in 2007 to enable the download and interchange of molecular interaction data. PSI-XML2.5 was designed to describe experimental data and to date has fulfilled this basic requirement. However, new use cases have arisen that the format cannot properly accommodate. These include data abstracted from more than one publication such as allosteric/cooperative interactions and protein complexes, dynamic interactions and the need to link kinetic and affinity data to specific mutational changes.
The Molecular Interaction workgroup of the HUPO-PSI has extended the existing, well-used XML interchange format for molecular interaction data to meet new use cases and enable the capture of new data types, following extensive community consultation. PSI-MI XML3.0 expands the capabilities of the format beyond simple experimental data, with a concomitant update of the tool suite which serves this format. The format has been implemented by key data producers such as the International Molecular Exchange (IMEx) Consortium of protein interaction databases and the Complex Portal.
PSI-MI XML3.0 has been developed by the data producers, data users, tool developers and database providers who constitute the PSI-MI workgroup. This group now actively supports PSI-MI XML2.5 as the main interchange format for experimental data, PSI-MI XML3.0 which additionally handles more complex data types, and the simpler, tab-delimited MITAB2.5, 2.6 and 2.7 for rapid parsing and download.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is an increasing evidence that populations of ectotherms can diverge genetically in response to different climatic conditions, both within their native range and (in the case of invasive ...species) in their new range. Here, we test for such divergence in invasive whitefly Bemisia tabaci populations in tropical Colombia, by considering heritable variation within and between populations in survival and fecundity under temperature stress, and by comparing population differences with patterns established from putatively neutral microsatellite markers. We detected significant differences among populations linked to mean temperature (for survival) and temperature variation (for fecundity) in local environments. A QST − FST analysis indicated that phenotypic divergence was often larger than neutral expectations (QST > FST). Particularly, for survival after a sublethal heat shock, this divergence remained linked to the local mean temperature after controlling for neutral divergence. These findings point to rapid adaptation in invasive whitefly likely to contribute to its success as a pest species. Ongoing evolutionary divergence also provides challenges in predicting the likely impact of Bemisia in invaded regions.
Group II introns are self-splicing catalytic RNAs that act as mobile retroelements. In bacteria, they are thought to be tolerated to some extent because they self-splice and home preferentially to ...sites outside of functional genes, generally within intergenic regions or in other mobile genetic elements, by mechanisms including the divergence of DNA target specificity to prevent target site saturation. RmInt1 is a mobile group II intron that is widespread in natural populations of Sinorhizobium meliloti and was first described in the GR4 strain. Like other bacterial group II introns, RmInt1 tends to evolve toward an inactive form by fragmentation, with loss of the 3' terminus. We identified genomic evidence of a fragmented intron closely related to RmInt1 buried in the genome of the extant S. meliloti/S. medicae species. By studying this intron, we obtained evidence for the occurrence of intron insertion before the divergence of ancient rhizobial species. This fragmented group II intron has thus existed for a long time and has provided sequence variation, on which selection can act, contributing to diverse genetic rearrangements, and to generate pan-genome divergence after strain differentiation. The data presented here suggest that fragmented group II introns within intergenic regions closed to functionally important neighboring genes may have been microevolutionary forces driving adaptive evolution of these rhizobial species.