Principles of meiotic chromosome assembly revealed in S. cerevisiae

During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from a proteinaceous axis, but the mechanisms of assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked to genomic sequence. As cells enter meiosis, we observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent of mammalian interphase organisation, but with distinct regulation. Meiotic patterns agree with simulations of loop extrusion with growth limited by barriers, in which a heterogeneous population of expanding loops develop along the chromosome. Importantly, CTCF, the factor that imposes similar features in mammalian interphase, is absent in S. cerevisiae, suggesting alternative mechanisms of barrier formation. While grid-like interactions emerge independently of meiotic chromosome synapsis, synapsis itself generates additional compaction that matures differentially according to telomere proximity and chromosome size. Collectively, our results elucidate fundamental principles of chromosome assembly and demonstrate the essential role of cohesin within this evolutionarily conserved process

MRI-based radiomics for prognosis of pediatric diffuse intrinsic pontine glioma: an international study.

Background: Diffuse intrinsic pontine gliomas (DIPGs) are lethal pediatric brain tumors. Presently, MRI is the mainstay of disease diagnosis and surveillance. We identify clinically significant computational features from MRI and create a prognostic machine learning model. Methods: We isolated tumor volumes of T1-post-contrast (T1) and T2-weighted (T2) MRIs from 177 treatment-naïve DIPG patients from an international cohort for model training and testing. The Quantitative Image Feature Pipeline and PyRadiomics was used for feature extraction. Ten-fold cross-validation of least absolute shrinkage and selection operator Cox regression selected optimal features to predict overall survival in the training dataset and tested in the independent testing dataset. We analyzed model performance using clinical variables (age at diagnosis and sex) only, radiomics only, and radiomics plus clinical variables. Results: All selected features were intensity and texture-based on the wavelet-filtered images (3 T1 gray-level co-occurrence matrix (GLCM) texture features, T2 GLCM texture feature, and T2 first-order mean). This multivariable Cox model demonstrated a concordance of 0.68 (95% CI: 0.61-0.74) in the training dataset, significantly outperforming the clinical-only model (C = 0.57 [95% CI: 0.49-0.64]). Adding clinical features to radiomics slightly improved performance (C = 0.70 [95% CI: 0.64-0.77]). The combined radiomics and clinical model was validated in the independent testing dataset (C = 0.59 [95% CI: 0.51-0.67], Noether's test P = .02). Conclusions: In this international study, we demonstrate the use of radiomic signatures to create a machine learning model for DIPG prognostication. Standardized, quantitative approaches that objectively measure DIPG changes, including computational MRI evaluation, could offer new approaches to assessing tumor phenotype and serve a future role for optimizing clinical trial eligibility and tumor surveillance

Broadband random optoelectronic oscillator

[EN] Random scattering of light in transmission media has attracted a great deal of attention in the field of photonics over the past few decades. An optoelectronic oscillator (OEO) is a microwave photonic system offering unbeatable features for the generation of microwave oscillations with ultra-low phase noise. Here, we combine the unique features of random scattering and OEO technologies by proposing an OEO structure based on random distributed feedback. Thanks to the random distribution of Rayleigh scattering caused by inhomogeneities within the glass structure of the fiber, we demonstrate the generation of ultra-wideband (up to 40¿GHz from DC) random microwave signals in an open cavity OEO. The generated signals enjoy random characteristics, and their frequencies are not limited by a fixed cavity length figure. The proposed device has potential in many fields such as random bit generation, radar systems, electronic interference and countermeasures, and telecommunications.Thanks N. Shi and Y. Yang for comments and discussion. This work was supported by the National Key Research and Development Program of China under 2018YFB2201902 and the National Natural Science Foundation of China under 61925505. This work was also partly supported by the National Key Research and Development Program of China under 2018YFB2201901, 2018YFB2201903, and the National Natural Science Foundation of China under 61535012 and 61705217.Ge, Z.; Hao, T.; Capmany Francoy, J.; Li, W.; Zhu, N.; Li, M. (2020). Broadband random optoelectronic oscillator. Nature Communications. 11(1):1-8. https://doi.org/10.1038/s41467-020-19596-xS18111Feng, S., Kane, C., Lee, P. A. & Stone, A. D. Correlations and fluctuations of coherent wave transmission through disordered media. Phys. Rev. Lett. 61, 834 (1988).Wiersma, D. 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Breaking the limitation of mode building time in an optoelectronic oscillator. Nat. Commun. 9, 1839 (2018).Zhang, W. & Yao, J. Silicon photonic integrated optoelectronic oscillator for frequency-tunable microwave generation. J. Lightwave Technol. 36, 4655–4663 (2018).Hao, T. et al. Toward Monolithic Integration of OEOs: from systems to chips. J. Lightwave Technol. 36, 4565–4582 (2018).Zhang, J. & Yao, J. Parity-time–symmetric optoelectronic oscillator. Sci. Adv. 4, eaar6782 (2018).Liu, Y. et al. Observation of parity-time symmetry in microwave photonics. Light Sci. Appl. 7, 38 (2018).Nakazawa, M. Rayleigh backscattering theory for single-mode optical fibers. JOSA 73, 1175–1180 (1983).Hartog, A. & Gold, M. On the theory of backscattering in single-mode optical fibers. J. Lightwave Technol. 2, 76–82 (1984).Eickhoff, W., & Ulrich, R. Statistics of backscattering in single-mode fiber. In Optical Fiber Communication Conference. Optical Society of America (1981).Alekseev, A. E., Tezadov, Y. A. & Potapov, V. T. Statistical properties of backscattered semiconductor laser radiation with different degrees of coherence. Quantum Electron 42, 76–81 (2012).Gysel, P. & Staubli, R. K. Statistical properties of Rayleigh backscattering in single-mode fibers. J. Lightwave Technol. 8, 561–567 (1990).Staubli, R. K. & Gysel, P. Statistical properties of single-mode fiber rayleigh backscattered intensity and resulting detector current. IEEE Trans. Commun. 40, 1091–1097 (1992).Levy, E. C., Horowitz, M. & Menyuk, C. R. Modeling optoelectronic oscillators. JOSA B 26, 148–159 (2009).Yariv, A. Introduction to Optical Electronics 2nd edn. (Holt, Rinehart and Winston, New York, 1976).Aoki, Y., Tajima, K. & Mito, I. Input power limits of single-mode optical fibers due to stimulated Brillouin scattering in optical communication systems. J. Lightwave Technol. 6, 710–719 (1988).Song, H. J., Shimizu, N., Kukutsu, N., Nagatsuma, T. & Kado, Y. 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Broadband chaotic signals and breather oscillations in an optoelectronic oscillator incorporating a microwave photonic filter. J. Lightwave Technol. 32, 3933–3942 (2014)

How should we assess knowledge translation in research organizations; designing a knowledge translation self-assessment tool for research institutes (SATORI)

<p>Abstract</p> <p>Background</p> <p>The knowledge translation self-assessment tool for research institutes (SATORI) was designed to assess the status of knowledge translation in research institutes. The objective was, to identify the weaknesses and strengths of knowledge translation in research centres and faculties associated with Tehran University of Medical Sciences (TUMS).</p> <p>Methods</p> <p>The tool, consisting of 50 statements in four main domains, was used in 20 TUMS-affiliated research centres and departments after its reliability was established. It was completed in a group discussion by the members of the research council, researchers and research users' representatives from each centre and/or department.</p> <p>Results</p> <p>The mean score obtained in the four domains of 'The question of research', 'Knowledge production', 'Knowledge transfer' and 'Promoting the use of evidence' were 2.26, 2.92, 2 and 1.89 (out of 5) respectively.</p> <p>Nine out of 12 interventional priorities with the lowest quartile score were related to knowledge transfer resources and strategies, whereas eight of them were in the highest quartile and related to 'The question of research' and 'Knowledge production'.</p> <p>Conclusions</p> <p>The self-assessment tool identifies the gaps in capacity and infrastructure of knowledge translation support within research organizations. Assessment of research institutes using SATORI pointed out that strengthening knowledge translation through provision of financial support for knowledge translation activities, creating supportive and facilitating infrastructures, and facilitating interactions between researchers and target audiences to exchange questions and research findings are among the priorities of research centres and/or departments.</p

Helicobacter pylori infection might be responsible for the interconnection between type 1 diabetes and autoimmune thyroiditis

<p>Abstract</p> <p>Background</p> <p>Higher serological prevalence rates of helicobacter pylori (H. pylori) infection have been reported in patients with type 1 diabetes (T1DM) and autoimmune thyroiditis (AT). Patients with T1DM are at increased risk for developing other autoimmune diseases, most commonly AT. It is unknown whether H. pylori infection could explain the high prevalence of thyroid autoantibodies and AT in T1DM. The aim of the current study was to evaluate anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) autoantibodies in correlation with anti-H. pylori IgG and IgA in young patients with T1DM.</p> <p>Methods</p> <p>Anti-H. Pylori IgG, IgA, anti-TPO and anti-Tg antibodies titers were measured in 162 euthyroid patients with T1DM and 80 healthy controls matched for age, sex and socioeconomic status.</p> <p>Results</p> <p>Seroprevalence of H. pylori was significantly higher in patients with T1DM than in healthy controls; 79% vs. 51.2%, p < 0.001. Anti H. pylori IgG was positive in 61.1% of patients with T1DM and 30% of controls, p < 0.001, anti H. pylori IgA was positive in 74% of patients with T1DM and 32.5% of controls, p < 0.001. Thyroid autoimmunity was also significantly higher in patients with T1DM than in controls; 56.7% vs. 6.2%, p < 0.001. Anti-TPO was positive in 25.3% of patients with T1DM and 3.7% of controls, p < 0.001, anti-Tg was positive in 47.5% of patients with T1DM and 6.2% of controls, p < 0.001. With simple and multiple regression analysis anti-H. pylori IgG and IgA titers were positively and significantly correlated with Anti-TPO and anti-Tg titers in patients with T1DM.</p> <p>Conclusion</p> <p>our results support the idea of a connection between H. pylori infection and the occurrence of anti-TPO, anti-Tg autoantibodies and AT in young patients with T1DM. So, H. pylori infection could be considered as an environmental trigger for development of AT in T1DM. Young patients with T1DM should be screened for H. pylori infection.</p

Chromium removal from aqueous solution by a PEI-silica nanocomposite

It is essential and important to determine the adsorption mechanism as well as removal efficiency when using an adsorption technique to remove toxic heavy metals from wastewater. In this research, the removal efficiency and mechanism of chromium removal by a silica-based nanoparticle were investigated. A PEI-silica nanoparticle was synthesized by a one-pot technique and exhibited uniformly well-dispersed PEI polymers in silica particles. The adsorption capacity of chromium ions was determined by a batch adsorption test, with the PEI-silica nanoparticle having a value of 183.7 mg/g and monolayer sorption. Adsorption of chromium ions was affected by the solution pH and altered the nanoparticle surface chemically. First principles calculations of the adsorption energies for the relevant adsorption configurations and XPS peaks of Cr and N showed that Cr(VI), [HCrO4](-) is reduced to two species, Cr(III), CrOH2+ and Cr3+, by an amine group and that Cr(III) and Cr(VI) ions are adsorbed on different functional groups, oxidized N and NH3+

High-Anxious Individuals Show Increased Chronic Stress Burden, Decreased Protective Immunity, and Increased Cancer Progression in a Mouse Model of Squamous Cell Carcinoma

In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2–3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED), 3 times/week, 10-weeks). The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome), and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th), cytolytic (CTL), and regulatory (Treg) T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF) by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden), increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression), lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity), and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis). These results suggest that the deleterious effects of high trait anxiety could be: exacerbated by life-stressors, accentuated by the stress of cancer diagnosis/treatment, and mediate increased tumor progression and/or metastasis. Therefore, it may be beneficial to investigate the use of chemotherapy-compatible anxiolytic treatments immediately following cancer diagnosis, and during cancer treatment/survivorship

Varying constants, Gravitation and Cosmology

Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. It is thus of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We thus detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, Solar system observations, meteorites dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.Comment: 145 pages, 10 figures, Review for Living Reviews in Relativit