Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease

AIM: To investigate the accuracy of fungal dysbiosis in mucosa and stool for predicting the diagnosis of Crohn’s disease (CD). METHODS: Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer’s protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve (AUC) was calculated. RESULTS: All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9 (range: 6.7-17.8) years for CD children and 13.9 (3.25-18.6) years for controls, and 10/15 (67%) of the CD and 13/20 (65%) of the control subjects were boys. CD locations at diagnosis were ileal (L1) in 4 and colonic (L3) in 11 children, while CD behavior was non-stricturing and non-penetrating (B1) in 12 and stricturing (B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools (AUC = 0.85 ± 0.057) than in mucosa (AUC = 0.71 ± 0.067) (P < 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for Saccharomyces cerevisiae and S. bayanus, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa. CONCLUSION: We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD. Key Words: Fungiome, Mycobiome, Crohn’s disease, Inflammation, Saudi children Core tip: We found high accuracy of fungal dysbiosis in predicting diagnosis of Crohn’s disease (CD), a finding similar to bacterial dysbiosis. However, the higher area under the curve for the fungal dysbiosis classifier in stool (0.85 ± 0.057) than in mucosa (0.71 ± 0.067) (P < 0.001), contrasts with bacterial studies, suggesting higher accuracy of stool samples. Although the clinical application of this finding is limited at present by the high cost of fungal analysis, such information is important from a scientific viewpoint, to increase the understanding of the role of fungal flora in CD and to stimulate further studies.The authors extend their appreciations to the Deanship of Scientific Research at King Saud University in Riyadh, Kingdom of Saudi Arabia for funding this work through Research Group No [RGP-1436-007]. This work was also supported by a grant from the Simons Foundation [No. 409704] to Kirill Korolev) and by the startup fund from Boston University to Kirill Korolev. Simulations were carried out on Shared Computing Cluster at Boston University. Rajita Menon was partially supported by a Hariri Graduate Fellowship from Boston University. Harland Winter, MD received support from Martin Schlaff and the Diane and Dorothy Brooks Foundation. (RGP-1436-007 - King Saud University in Riyadh, Kingdom of Saudi Arabia; 409704 - Simons Foundation; Boston University; Hariri Graduate Fellowship from Boston University; Diane and Dorothy Brooks Foundation)Published versio

Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data

&lt;p&gt;Purpose: DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.&lt;/p&gt; &lt;p&gt;Methods: The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.&lt;/p&gt; &lt;p&gt;Results: The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.&lt;/p&gt; &lt;p&gt;Conclusion: This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.&lt;/p&gt

Chromatin and epigenetics: current biophysical views

Recent advances in high-throughput sequencing experiments and their theoretical descriptions have determined fast dynamics of the "chromatin and epigenetics" field, with new concepts appearing at high rate. This field includes but is not limited to the study of DNA-protein-RNA interactions, chromatin packing properties at different scales, regulation of gene expression and protein trafficking in the cell nucleus, binding site search in the crowded chromatin environment and modulation of physical interactions by covalent chemical modifications of the binding partners. The current special issue does not pretend for the full coverage of the field, but it rather aims to capture its development and provide a snapshot of the most recent concepts and approaches. Eighteen open-access articles comprising this issue provide a delicate balance between current theoretical and experimental biophysical approaches to uncover chromatin structure and understand epigenetic regulation, allowing free flow of new ideas and preliminary results

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal

The role of dipole interactions in hyperthermia heating colloidal clusters of densely-packed superparamagnetic nanoparticles

This work aims to investigate the influence of inter-particle dipole interactions on hyperthermia heating colloidal clusters of densely-packed Fe3O4 nanoparticles at low field intensity. Emulsion droplet solvent evaporation method was used to assemble oleic acid modified Fe3O4 particles into compact clusters which were stabilized by surfactant in water. Both experimental and simulation works were conducted to study their heating performance at different cluster’s sizes. The dipole interactions improve the heating only when the clusters are small enough to bring an enhancement in clusters’ shape anisotropy. The shape anisotropy is reduced at greater clusters’ sizes, since the shapes of the clusters become more and more spherical. Consequently, the dipole interactions change to impair the heating efficiency at larger sizes. When the clusters are totally isotropic in shape, the heating efficiency is lower than that of non-interacting particles despite the cluster’s size, although the efficiency increases by a little bit at a particular size most likely due to the dipole couplings. In these situations, one has to use particles with higher magnetic anisotropy and/or saturation magnetization to improve the heating

The role of Allee effect in modelling post resection recurrence of glioblastoma

Resection of the bulk of a tumour often cannot eliminate all cancer cells, due to their infiltration into the surrounding healthy tissue. This may lead to recurrence of the tumour at a later time. We use a reaction-diffusion equation based model of tumour growth to investigate how the invasion front is delayed by resection, and how this depends on the density and behaviour of the remaining cancer cells. We show that the delay time is highly sensitive to qualitative details of the proliferation dynamics of the cancer cell population. The typically assumed logistic type proliferation leads to unrealistic results, predicting immediate recurrence. We find that in glioblastoma cell cultures the cell proliferation rate is an increasing function of the density at small cell densities. Our analysis suggests that cooperative behaviour of cancer cells, analogous to the Allee effect in ecology, can play a critical role in determining the time until tumour recurrence

Measurement of polarization amplitudes and CP asymmetries in B-0 -> phi K*(892)(0)

An angular analysis of the decay B (0) -> phi K (*)(892)(0) is reported based on a pp collision data sample, corresponding to an integrated luminosity of 1.0 fb(-1), collected at a centre-of-mass energy of root S = 7 TeV with the LHCb detector. The P-wave amplitudes and phases are measured with a greater precision than by previous experiments, and confirm about equal amounts of longitudinal and transverse polarization. The S-wave K+ pi(-) and K+ K- contributions are taken into account and found to be significant. A comparison of the B (0) -> phi K (*)(892)(0) and results shows no evidence for direct CP violation in the rate asymmetry, in the triple-product asymmetries or in the polarization amplitudes and phases

Search for the rare decay K0S→μ+μ−

A search for the decay K0S→μ+μ− is performed, based on a data sample of 1.0 fb−1 of pp collisions at &#8730;&lt;span style="text-decoration:overline"&gt;s&lt;/span&gt;=7 TeV collected by the LHCb experiment at the Large Hadron Collider. The observed number of candidates is consistent with the background-only hypothesis, yielding an upper limit of B(K0S→μ+μ−) &#60; 11(9) × 10−9 at 95 (90)% confidence level. This limit is a factor of thirty below the previous measurement