Systemic lupus erythematosus (SLE) is a complex, inflammatory autoimmune disease that affects multiple organ systems. We used global gene expression profiling of peripheral blood mononuclear cells to ...identify distinct patterns of gene expression that distinguish most SLE patients from healthy controls. Strikingly, about half of the patients studied showed dysregulated expression of genes in the IFN pathway. Furthermore, this IFN gene expression "signature" served as a marker for more severe disease involving the kidneys, hematopoetic cells, and/or the central nervous system. These results provide insights into the genetic pathways underlying SLE, and identify a subgroup of patients who may benefit from therapies targeting the IFN pathway.
Femtosecond pulses from X-ray free-electron lasers offer a powerful method for observing the coherent dynamic of phonons in crystalline materials, it is now shown. This time-resolved spectroscopic ...tool could provide insight into low-energy collective excitations in solids and how they interact at a microscopic level to determine the material's macroscopic properties.
Intense femtosecond laser excitation can produce transient states of matter that would otherwise be inaccessible to laboratory investigation. At high excitation densities, the interatomic forces that ...bind solids and determine many of their properties can be substantially altered. Here, we present the detailed mapping of the carrier density-dependent interatomic potential of bismuth approaching a solid-solid phase transition. Our experiments combine stroboscopic techniques that use a high-brightness linear electron accelerator-based x-ray source with pulse-by-pulse timing reconstruction for femtosecond resolution, allowing quantitative characterization of the interatomic potential energy surface of the highly excited solid.
In a genome-wide association study (GWAS) of individuals of European ancestry afflicted with systemic lupus erythematosus (SLE) the extensive utilization of imputation, step-wise multiple regression, ...lasso regularization and increasing study power by utilizing false discovery rate instead of a Bonferroni multiple test correction enabled us to identify 13 novel non-human leukocyte antigen (HLA) genes and confirmed the association of four genes previously reported to be associated. Novel genes associated with SLE susceptibility included two transcription factors (EHF and MED1), two components of the NF-κB pathway (RASSF2 and RNF114), one gene involved in adhesion and endothelial migration (CNTN6) and two genes involved in antigen presentation (BIN1 and SEC61G). In addition, the strongly significant association of multiple single-nucleotide polymorphisms (SNPs) in the HLA region was assigned to HLA alleles and serotypes and deconvoluted into four primary signals. The novel SLE-associated genes point to new directions for both the diagnosis and treatment of this debilitating autoimmune disease.
In this two-part study, we investigate the motion of rigid, active objects in shear Stokes flow, focusing on bodies that induce rapid rotation as part of their activity. In Part 2, we derive and ...analyse governing equations for rapidly spinning complex-shaped particles – general helicoidal objects with chirality. Using the multiscale framework that we develop in Part 1 (Dalwadi et al., J. Fluid Mech., vol. 979, 2024, A1), we systematically derive emergent equations of motion for the angular and translational dynamics of these chiral spinning objects. We show that the emergent dynamics due to rapid rotation can be described by effective generalised Jeffery's equations, which differ from the classic versions via the inclusion of additional terms that account for chirality and other asymmetries. Furthermore, we use our analytic results to characterise and quantify the explicit effect of rotation on the effective hydrodynamic shape of the chiral objects, expanding significantly the scope of Jeffery's seminal study.
The observed behaviour of passive objects in simple flows can be surprisingly intricate, and is complicated further by object activity. Inspired by the motility of bacterial swimmers, in this ...two-part study we examine the three-dimensional motion of rigid active particles in shear Stokes flow, focusing on bodies that induce rapid rotation as part of their activity. In Part 1 we develop a multiscale framework to investigate these emergent dynamics and apply it to simple spheroidal objects. In Part 2 (Dalwadi et al., J. Fluid Mech., vol. 979, 2024, A2) we apply our framework to understand the emergent dynamics of more complex shapes; helicoidal objects with chirality. Via a multiple scales asymptotic analysis for nonlinear systems, we systematically derive emergent equations of motion for long-term trajectories that explicitly account for the strong (leading-order) effects of fast spinning. Supported by numerical examples, we constructively link these effective dynamics to the well-known Jeffery's orbits for passive spheroids, deriving an explicit closed-form expression for the effective shape of the active particle, broadening the scope of Jeffery's seminal study to spinning spheroids.
A simple model for the motion of shape-changing swimmers in Poiseuille flow was recently proposed and numerically explored by Omori et al. (J. Fluid Mech., vol. 930, 2022, A30). These explorations ...hinted that a small number of interacting mechanics can drive long-time behaviours in this model, cast in the context of the well-studied alga Chlamydomonas and its rheotactic behaviours in such flows. Here, we explore this model analytically via a multiple-scale asymptotic analysis, seeking to formally identify the causal factors that shape the behaviour of these swimmers in Poiseuille flow. By capturing the evolution of a Hamiltonian-like quantity, we reveal the origins of the long-term drift in a single swimmer-dependent constant, whose sign determines the eventual behaviour of the swimmer. This constant captures the nonlinear interaction between the oscillatory speed and effective hydrodynamic shape of deforming swimmers, driving drift either towards or away from rheotaxis.
Summary
Background
Gestational diabetes mellitus (GDM) is associated+ with adverse pregnancy outcomes compared with women with normal glucose tolerance in pregnancy. The WHO recommends screening at ...24–28 weeks gestation for GDM. Women who are diagnosed before 24–28 weeks gestation have a longer intervention period which may impact positively on pregnancy outcomes.
Aim
This study aimed to examine pregnancy outcomes of women with GDM diagnosed <24 weeks gestation compared with those diagnosed at 24–28 weeks in a large Irish cohort.
Methods
A retrospective cohort study of 1471 pregnancies in women with GDM diagnosed using IADPSG criteria between September 2012 and April 2016 was conducted. At GDM diagnosis, women were classified as early GDM <24 weeks or standard GDM 24–28 weeks gestation.
Results
Women with early GDM had a significantly greater risk of pregnancy-induced hypertension (12.4% vs. 5.3%; P < 0.05), post-partum haemorrhage (8.7% vs. 2.4%; P < 0.05) and post-partum glucose abnormalities (32% vs. 15.6%; P < 0.05). Their offspring had a greater risk of pre-maturity (10.9% vs. 6.6%; P < 0.05), stillbirth (1.4% vs. 0.5%; P < 0.05), large for gestational age (19.1% vs. 13.4% P < 0.05) and need neonatal intensive care (30.7% vs. 22.1%; P < 0.05) compared with offspring of women with standard GDM. Rates of C-section and pre-maturity were still higher in the early GDM group when the two groups where compared based on their post-natal OGTT.
Conclusion
Early GDM women and their offspring are at greater risk of an adverse pregnancy outcome compared with those diagnosed at 24–28 weeks. In view of the abnormal post-natal glucose findings, early GDM may reflect a more advanced state in diabetes pathogenesis.
Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation ...within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies.
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