First-in-Human Phase 1 Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of DISC-0974, an Anti-Hemojuvelin Antibody, in Healthy Participants.

Pathologic elevations in hepcidin, a key regulator of iron homeostasis, contribute to anemia of inflammation in chronic disease. DISC-0974 is a monoclonal antibody that binds to hemojuvelin and blocks bone morphogenetic protein signaling, thereby suppressing hepcidin production. Reduction of systemic hepcidin levels is predicted to increase iron absorption and mobilize stored iron into circulation, where it may be utilized by red blood cell (RBC) precursors in the bone marrow to improve hemoglobin levels and to potentially alleviate anemia of inflammation.

ABO Genotyping finds more A to B kidney transplant opportunities than lectin-based subtyping.

ABO compatibility is important for kidney transplantation, with longer waitlist times for blood group B kidney transplant candidates. However, kidneys from non-A (eg, A) subtype donors, which express less A antigen, can be safely transplanted into group B recipients. ABO subtyping is routinely performed using anti-A lectin, but DNA-based genotyping is also possible.

A Phase IIb Randomized Clinical Study of an Anti-αβ Monoclonal Antibody in Idiopathic Pulmonary Fibrosis.

Treatment options for idiopathic pulmonary fibrosis (IPF) are limited. To evaluate the efficacy and safety of BG00011, an anti-αβ IgG1 monoclonal antibody, in the treatment of patients with IPF. In a phase IIb randomized, double-blind, placebo-controlled trial, patients with IPF (FVC ⩾50% predicted, on or off background therapy) were randomized 1:1 to once-weekly subcutaneous BG00011 56 mg or placebo.

Rates of Fentanyl Positivity in Neonatal Urine Following Maternal Analgesia During Labor and Delivery.

Background: Fentanyl is commonly given as an analgesic during labor and delivery. The extent of transplacental drug transfer and fetal exposure is not well studied. We analyzed the relationship between neonatal urine fentanyl results and various peripartum factors.

Utility of a Simple and Robust Flow Cytometry Assay for Rapid Clonality Testing in Mature Peripheral T-Cell Lymphomas.

Objectives: Flow cytometry immunophenotyping is limited by poor resolution of T-cell clones. A newly described antibody was recently used to distinguish normal peripheral blood T cells from malignant T-cell clones. Here, we evaluate this antibody as a new diagnostic tool for detecting T-cell clonality in mature peripheral T-cell lymphomas.

Unique developmental trajectories and genetic regulation of ventricular and outflow tract progenitors in the zebrafish second heart field.

During mammalian embryogenesis, cardiac progenitor cells constituting the second heart field (SHF) give rise to the right ventricle and primitive outflow tract (OFT). In zebrafish, previous lineage-tracing and mutant analyses suggested that SHF ventricular and OFT progenitors co-migrate to the arterial pole of the zebrafish heart tube soon after their specification in the field of anterior lateral plate mesoderm (ALPM). Using additional prospective lineage tracing, we demonstrate that while SHF ventricular progenitors migrate directly to the arterial pole, OFT progenitors become temporarily sequestered in the mesodermal cores of pharyngeal arch 2 (PA2), where they downregulate expression.

The AP-1 transcription factor component Fosl2 potentiates the rate of myocardial differentiation from the zebrafish second heart field.

The vertebrate heart forms through successive phases of cardiomyocyte differentiation. Initially, cardiomyocytes derived from first heart field (FHF) progenitors assemble the linear heart tube. Thereafter, second heart field (SHF) progenitors differentiate into cardiomyocytes that are accreted to the poles of the heart tube over a well-defined developmental window.

Tmem88a mediates GATA-dependent specification of cardiomyocyte progenitors by restricting WNT signaling.

Biphasic control of WNT signaling is essential during cardiogenesis, but how the pathway switches from promoting cardiac mesoderm to restricting cardiomyocyte progenitor fate is unknown. We identified genes expressed in lateral mesoderm that are dysregulated in zebrafish when both gata5 and gata6 are depleted, causing a block to cardiomyocyte specification. This screen identified tmem88a, which is expressed in the early cardiac progenitor field and was previously implicated in WNT modulation by overexpression studies.

Disruption of topoisomerase II perturbs pairing in drosophila cell culture.

Homolog pairing refers to the alignment and physical apposition of homologous chromosomal segments. Although commonly observed during meiosis, homolog pairing also occurs in nonmeiotic cells of several organisms, including humans and Drosophila. The mechanism underlying nonmeiotic pairing, however, remains largely unknown.