Numb Suppresses Notch-Dependent Activation of during Lateral Inhibition in the Embryonic Nervous System.

The role of in regulating Notch signaling and neurogenesis has been extensively studied, with a particular focus on its effects on the peripheral nervous system (PNS). Previous studies based on a single loss-of-function allele of , , showed an antineurogenic effect on the peripheral nervous system (PNS), which revealed that the wild-type suppresses Notch signaling. In the current study, we examined whether this phenotype is consistently observed in loss-of-function mutations of Two more alleles, and , were shown to have an antineurogenic phenotype in the PNS.

Nutrient-driven dedifferentiation of enteroendocrine cells promotes adaptive intestinal growth in Drosophila.

Post-developmental organ resizing improves organismal fitness under constantly changing nutrient environments. Although stem cell abundance is a fundamental determinant of adaptive resizing, our understanding of its underlying mechanisms remains primarily limited to the regulation of stem cell division. Here, we demonstrate that nutrient fluctuation induces dedifferentiation in the Drosophila adult midgut to drive adaptive intestinal growth.

Estimation of crossbridge-state during cardiomyocyte beating using second harmonic generation.

Estimation of dynamic change of crossbridge formation in living cardiomyocytes is expected to provide crucial information for elucidating cardiomyopathy mechanisms, efficacy of an intervention, and others. Here, we established an assay system to dynamically measure second harmonic generation (SHG) anisotropy derived from myosin filaments depended on their crossbridge status in pulsating cardiomyocytes. Experiments utilizing an inheritable mutation that induces excessive myosin-actin interactions revealed that the correlation between sarcomere length and SHG anisotropy represents crossbridge formation ratio during pulsation.

Sample Preparation and Imaging of the Pupal Drosophila Abdominal Epidermis.

The epithelium is one of the best studied tissues for morphogenesis, pattern formation, cell polarity, cell division, cell competition, tumorigenesis, and metastatic behaviors. However, it has been challenging to analyze real-time cell interactions or cell dynamics within the epithelia under physiological conditions. The Drosophila pupal abdominal epidermis is a model system that allows to combine long-term real-time imaging under physiological conditions with the use of powerful Drosophila genetics tools.

Protocol design and synopsis: Omalizumab as Monotherapy and as Adjunct Therapy to Multiallergen OIT in Children and Adults with Food Allergy (OUtMATCH).

Background: Food allergy is common and causes substantial morbidity and even mortality. Safe and effective treatments for food allergy would therefore be highly desirable, especially for individuals with multiple food allergies.

Objectives: Our aim was to describe a phase 3 study on treatment of patients with multiple food allergies with omalizumab.

Cell mechanics and cell-cell recognition controls by Toll-like receptors in tissue morphogenesis and homeostasis.

Signal transduction by the Toll-like receptors (TLRs) is conserved and essential for innate immunity in metazoans. The founding member of the TLR family, Toll-1, was initially identified for its role in dorsoventral axis formation in early embryogenesis. The genome encodes nine TLRs that display dynamic expression patterns during development, suggesting their involvement in tissue morphogenesis and homeostasis.

High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy.

Peanut allergy can result in life-threatening reactions and is a major public health concern. Oral immunotherapy (OIT) induces desensitization to food allergens through administration of increasing amounts of allergen. To dissect peanut-specific immunoglobulin E (IgE) and IgG responses in subjects undergoing OIT, we have developed AllerScan, a method that leverages phage-display and next-generation sequencing to identify the epitope targets of peanut-specific antibodies.

Differential cell adhesion implemented by Drosophila Toll corrects local distortions of the anterior-posterior compartment boundary.

Maintaining lineage restriction boundaries in proliferating tissues is vital to animal development. A long-standing thermodynamics theory, the differential adhesion hypothesis, attributes cell sorting phenomena to differentially expressed adhesion molecules. However, the contribution of the differential adhesion system during tissue morphogenesis has been unsubstantiated despite substantial theoretical support.

Reduction of endocytic activity accelerates cell elimination during tissue remodeling of the epidermal epithelium.

Epithelial tissues undergo cell turnover both during development and for homeostatic maintenance. Cells that are no longer needed are quickly removed without compromising the barrier function of the tissue. During metamorphosis, insects undergo developmentally programmed tissue remodeling.

Author Correction: Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy.

The role of dysbiosis in food allergy (FA) remains unclear. We found that dysbiotic fecal microbiota in FA infants evolved compositionally over time and failed to protect against FA in mice. Infants and mice with FA had decreased IgA and increased IgE binding to fecal bacteria, indicative of a broader breakdown of oral tolerance than hitherto appreciated.

Blockade of RGMb inhibits allergen-induced airways disease.

Background: Allergic asthma causes morbidity in many subjects, and novel precision-directed treatments would be valuable.

Objective: We sought to examine the role of a novel innate molecule, repulsive guidance molecule b (RGMb), in murine models of allergic asthma.

Methods: In models of allergic asthma using ovalbumin or cockroach allergen, mice were treated with anti-RGMb or control mAb and examined for airway inflammation and airway hyperreactivity (AHR), a cardinal feature of asthma.

Long-Term Outcome of Peanut Oral Immunotherapy Facilitated Initially by Omalizumab.

Background: We successfully used omalizumab to facilitate peanut oral immunotherapy (OIT) in children with reactivity to ≤50mg peanut protein and with high peanut IgE (median, 229 kU/L).

Objective: We report on long-term OIT outcomes in these patients, including dosing changes, adverse events, peanut immunoglobulin changes, and quality of life (QoL).

Methods: Patients were followed for up to 72 months (67 months of maintenance).

Competition for Space Is Controlled by Apoptosis-Induced Change of Local Epithelial Topology.

During the initial stage of tumor progression, oncogenic cells spread despite spatial confinement imposed by surrounding normal tissue. This spread of oncogenic cells (winners) is thought to be governed by selective killing of surrounding normal cells (losers) through a phenomenon called "cell competition" (i.e.

A natural killer T-cell subset that protects against airway hyperreactivity.

Background: Infection of suckling mice with influenza virus expands a CD4CD8 double-negative (DN) natural killer T (NKT) cell subpopulation that protects the mice as adults against allergen-induced airway hyperreactivity (AHR). However, this NKT cell subset has not been characterized, and the underlying mechanisms of protection remain unknown.

Objective: We characterized this specific NKT cell subpopulation that developed during influenza infection in neonatal mice and that suppressed the subsequent development of AHR.

Oral immunotherapy with omalizumab reverses the Th2 cell-like programme of regulatory T cells and restores their function.

Background: Oral immunotherapy (OIT) successfully desensitizes patients with food allergies, but the immune mechanisms mediating its efficacy remain obscure.

Objectives: We tested the hypothesis that allergen-specific regulatory T (Treg) cell function is impaired in food allergy and is restored by anti-IgE antibody (omalizumab)-supplemented OIT.

Methods: Peanut-specific T effector (Teff) and Treg cell proliferative responses, activation markers and cytokine expression were analysed by flow cytometry in 13 peanut-allergic subjects before the start of omalizumab-supplemented OIT and periodically in some subjects thereafter for up to 2 years.

Inference of Cell Mechanics in Heterogeneous Epithelial Tissue Based on Multivariate Clone Shape Quantification.

Cell populations in multicellular organisms show genetic and non-genetic heterogeneity, even in undifferentiated tissues of multipotent cells during development and tumorigenesis. The heterogeneity causes difference of mechanical properties, such as, cell bond tension or adhesion, at the cell-cell interface, which determine the shape of clonal population boundaries via cell sorting or mixing. The boundary shape could alter the degree of cell-cell contacts and thus influence the physiological consequences of sorting or mixing at the boundary (e.

Planar polarized contractile actomyosin networks in dynamic tissue morphogenesis.

The complex shapes of animal bodies are constructed through a sequence of simple physical interactions of constituent cells. Mechanical forces generated by cellular activities, such as division, death, shape change and rearrangement, drive tissue morphogenesis. By confining assembly or disassembly of actomyosin networks within the three-dimensional space of the cell, cells can localize forces to induce tissue deformation.

Omalizumab facilitates rapid oral desensitization for peanut allergy.

Background: Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions.

Objective: We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients.