Haploinsufficiency of the Notch Ligand DLL1 Causes Variable Neurodevelopmental Disorders.

Notch signaling is an established developmental pathway for brain morphogenesis. Given that Delta-like 1 (DLL1) is a ligand for the Notch receptor and that a few individuals with developmental delay, intellectual disability, and brain malformations have microdeletions encompassing DLL1, we hypothesized that insufficiency of DLL1 causes a human neurodevelopmental disorder. We performed exome sequencing in individuals with neurodevelopmental disorders.

Amyloid β perturbs elevated heme flux induced with neuronal development.

Introduction: Heme is a central molecule in mitochondrial respiration and ATP generation in neuronal cells. Thus, we assessed the importance of altered heme metabolism in Alzheimer's disease (AD) pathogenesis.

Methods: To investigate the role of altered heme metabolism in AD, we identified heme-related proteins whose expression is altered in AD patients and mouse models exhibiting amyloid pathology.

Cyclopamine tartrate, a modulator of hedgehog signaling and mitochondrial respiration, effectively arrests lung tumor growth and progression.

Lung cancer remains the leading cause of cancer-related death, despite the advent of targeted therapies and immunotherapies. Therefore, it is crucial to identify novel molecular features unique to lung tumors. Here, we show that cyclopamine tartrate (CycT) strongly suppresses the growth of subcutaneously implanted non-small cell lung cancer (NSCLC) xenografts and nearly eradicated orthotopically implanted NSCLC xenografts.

Essential roles of mitochondrial and heme function in lung cancer bioenergetics and tumorigenesis.

Contrary to Warburg's hypothesis, mitochondrial oxidative phosphorylation (OXPHOS) contributes significantly to fueling cancer cells. Several recent studies have demonstrated that radiotherapy-resistant and chemotherapy-resistant cancer cells depend on OXPHOS for survival and progression. Several cancers exhibit an increased risk in association with heme intake.

Correction to: A holistic view of cancer bioenergetics: mitochondrial function and respiration play fundamental roles in the development and progression of diverse tumors.

In this Correction, the authors would like to acknowledge that the original publication of the article "A holistic view of cancer bioenergetics: mitochondrial function and respiration play fundamental roles in the development and progression of diverse tumors" [1] was supported by CPRIT (Cancer Prevention & Research Institute of Texas) Grant RP160617.

The vascular disrupting agent combretastatin A-4 phosphate causes prolonged elevation of proteins involved in heme flux and function in resistant tumor cells.

Vascular disrupting agents (VDAs) represent a promising class of anti-cancer drugs for solid tumor treatment. Here, we aim to better understand the mechanisms underlying tumor reccurrence and treatment resistance following the administration of a VDA, combretastatin A-4 phosphate (CA4P). Firstly, we used photoacoustic tomography to noninvasively map the effect of CA4P on blood oxygen levels throughout subcutaneous non-small cell lung cancer (NSCLC) tumors in mice.

A holistic view of cancer bioenergetics: mitochondrial function and respiration play fundamental roles in the development and progression of diverse tumors.

Since Otto Warburg made the first observation that tumor cells exhibit altered metabolism and bioenergetics in the 1920s, many scientists have tried to further the understanding of tumor bioenergetics. Particularly, in the past decade, the application of the state-of the-art metabolomics and genomics technologies has revealed the remarkable plasticity of tumor metabolism and bioenergetics. Firstly, a wide array of tumor cells have been shown to be able to use not only glucose, but also glutamine for generating cellular energy, reducing power, and metabolic building blocks for biosynthesis.

Interval appendectomy after perforated appendicitis: what are the operative risks and luminal patency rates?

Background: The need for interval appendectomy after nonoperative management of a perforated appendicitis is being questioned owing to recent studies that estimated recurrence rates as low as 5% because of obliteration of the appendiceal lumen. We review our experience with interval appendectomy in this subset of patients to determine the postoperative outcomes and luminal patency rates.

Methods: A retrospective review was conducted of all children treated nonoperatively for a perforated appendicitis followed by elective interval appendectomy during the past 10 years.

Opioid consumption following outpatient upper extremity surgery.

Purpose: After elective outpatient upper extremity surgery, patients' need for opioid analgesic medication may be considerably less than typically dispensed. Our goal for this study was to evaluate pain control and quantify the amount of leftover pain medication.

Methods: We recruited patients scheduled for elective outpatient upper extremity surgery, who met the inclusion criteria, to participate in a phone interview 7 to 14 days after surgery.