REACTIN: Regulatory Activity Inference of Transcription Factors Underlying Human Diseases with Application to Breast Cancer

Genetic alterations of transcription factors (TFs) have been implicated in the tumorigenesis of cancers. In many cancers, alteration of TFs results in aberrant activity of them without changing their gene expression level. Gene expression data from microarray or RNA-seq experiments can capture the expression change of genes, however, it is still challenge to reveal the activity change of TFs. Here we propose a method, called REACTIN (REgulatory ACTivity INference), which integrates TF binding data with gene expression data to identify TFs with significantly differential activity between disease and normal samples. REACTIN successfully detect differential activity of estrogen receptor (ER) between ER+ and ER- samples in 10 breast cancer datasets. When applied to compare tumor and normal breast samples, it reveals TFs that are critical for carcinogenesis of breast cancer. Moreover, Reaction can be utilized to identify transcriptional programs that are predictive to patient survival time of breast cancer patients

Deferoxamine retinopathy: spectral domain-optical coherence tomography findings

Al-Djamiʿ li Ibn al-BaïtharNumérisation effectuée à partir d'un document de substitution

Deferoxamine retinopathy: spectral domain-optical coherence tomography findings

BACKGROUND: To describe the spectral domain optical coherence tomography (SD-OCT) findings of a patient who developed pigmentary retinopathy following high-dose deferoxamine administration. CASE PRESENTATION: A 34-year-old man with thalassemia major complained of nyctalopia and decreased vision following high-dose intravenous deferoxamine to treat systemic iron overload. Fundus examination revealed multiple discrete hypo-pigmented lesions at the posterior pole and mid-peripheral retina. Recovery was partial following cessation of desferrioxamine six weeks later. A follow-up SD-OCT showed multiple accumulated hyper-reflective deposits primarily in the choroid, retina pigment epithelium (RPE), and inner segment and outer segment (IS/OS) junction. CONCLUSION: Deferoxamine retinopathy primarily targets the RPE–Bruch membrane–photoreceptor complex, extending from the peri-fovea to the peripheral retina with foveola sparing. An SD-OCT examination can serve as a simple, noninvasive tool for early detection and long-term follow-up

Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors.

IntroductionThe interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.MethodsHuman CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-kappaB ligand (RANKL). Osteoclast differentiation was evaluated by gene expression, flow cytometry, tartrate-resistant acid phosphatase staining, fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type (Wt) and IL-17A-/- mice using micro-computer tomography and serum RANKL/osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A-/- and Wt mice.ResultsIL-17A upregulates the receptor activator for NF-kappaB receptor on human osteoclast precursors in vitro, leading to increased sensitivity to RANKL signalling, osteoclast differentiation and bone loss. IL-17A-/- mice have physiological bone homeostasis indistinguishable from Wt mice, and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts.ConclusionsCollectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases

Paper-Based ELISA: A Novel Diagnostic Approach for Monitoring Aqueous Humour VEGF Level in Ocular Diseases

We commonly diagnose ocular diseases via both morphological changes and symptoms. It is necessary to develop biochemically based assays for early or follow-up diagnosis of these diseases with a focus on robustness and ease of handling. To lay out a prospective path toward this goal, we describe and propose the use of ultrahigh sensitive paper-based ELISA (p-ELISA), which uses a treated piece of filter paper to monitor the activity of ocular diseases (i.e., detecting the vascular endothelial growth factor (VEGF) concentration in aqueous humour for proliferative diabetic retinopathy or age-related macular degeneration diagnosis). The advantages of p-ELISA include the following: (1) the capacity to directly measure biomarker concentrations in aqueous humour using only a tiny sample volume (as little as 2 μL); (2) significantly increased sensitivity compared to conventional ELISA (fg/mL levels); and (3) inexpensive materials and a short operation duration. P-ELISA is a novel point-of-care diagnostic tool with the significant potential to advance ophthalmological treatment guidelines by facilitating early detection and routinely monitoring therapeutic response

Field-Free Switching in Symmetry Breaking Multilayers: The Critical Role of Interlayer Chiral Exchange

It is crucial to realize field-free, deterministic, current-induced switching in spin-orbit torque magnetic random-access memory (SOT-MRAM) with perpendicular magnetic anisotropy (PMA). A tentative solution has emerged recently, which employs the interlayer chiral exchange coupling or the interlayer Dzyaloshinskii-Moriya interaction (i-DMI) to achieve symmetry breaking. We hereby investigate the interlayer DMI in a Pt/Co multilayer system with orthogonally magnetized layers, using repeatedly stacked [Pt/Co]n structure with PMA, and a thick Co layer with in-plane magnetic anisotropy (IMA). We clarify the origin and the direction of such symmetry breaking with relation to the i-DMI effective field, and show a decreasing trend of the said effective field magnitude to the stacking number (n). By comparing the current-induced field-free switching behavior for both PMA and IMA layers, we confirm the dominating role of i-DMI in such field-free switching, excluding other possible mechanisms such as tilted-anisotropy and unconventional spin currents that may have arisen from the symmetry breaking