Metabolic Bypass Rescues Aberrant S-nitrosylation-Induced TCA Cycle Inhibition and Synapse Loss in Alzheimer's Disease Human Neurons.

In Alzheimer's disease (AD), dysfunctional mitochondrial metabolism is associated with synaptic loss, the major pathological correlate of cognitive decline. Mechanistic insight for this relationship, however, is still lacking. Here, comparing isogenic wild-type and AD mutant human induced pluripotent stem cell (hiPSC)-derived cerebrocortical neurons (hiN), evidence is found for compromised mitochondrial energy in AD using the Seahorse platform to analyze glycolysis and oxidative phosphorylation (OXPHOS).

Endogenous S-nitrosocysteine proteomic inventories identify a core of proteins in heart metabolic pathways.

Protein cysteine residues are essential for protein folding, participate in enzymatic catalysis, and coordinate the binding of metal ions to proteins. Enzymatically catalyzed and redox-dependent post-translational modifications of cysteine residues are also critical for signal transduction and regulation of protein function and localization. S-nitrosylation, the addition of a nitric oxide equivalent to a cysteine residue, is a redox-dependent modification.

International Classification of Retinopathy of Prematurity, Third Edition.

Purpose: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.

Author Correction: African-centric TP53 variant increases iron accumulation and bacterial pathogenesis but improves response to malaria toxin.

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

African-centric TP53 variant increases iron accumulation and bacterial pathogenesis but improves response to malaria toxin.

A variant at amino acid 47 in human TP53 exists predominantly in individuals of African descent. P47S human and mouse cells show increased cancer risk due to defective ferroptosis. Here, we show that this ferroptotic defect causes iron accumulation in P47S macrophages.

Diagnosis and Management of Mild Traumatic Brain Injury in Children: A Systematic Review.

Importance: In recent years, there has been an exponential increase in the research guiding pediatric mild traumatic brain injury (mTBI) clinical management, in large part because of heightened concerns about the consequences of mTBI, also known as concussion, in children. The CDC National Center for Injury Prevention and Control's (NCIPC) Board of Scientific Counselors (BSC), a federal advisory committee, established the Pediatric Mild TBI Guideline workgroup to complete this systematic review summarizing the first 25 years of literature in this field of study.

Objective: To conduct a systematic review of the pediatric mTBI literature to serve as the foundation for an evidence-based guideline with clinical recommendations associated with the diagnosis and management of pediatric mTBI.

Longitudinal study of the association between thrombocytopenia and retinopathy of prematurity.

Background: An association between thrombocytopenia and retinopathy of prematurity (ROP) has been suggested but not been studied longitudinally. We sought to identify the time period in postnatal development during which thrombocytopenia and the subsequent development of severe ROP are associated.

Methods: This was a retrospective case-control study of 100 subjects who received laser photocoagulation for type 1 ROP between 2005 and 2009 and 100 controls with no ROP or only stage 1 ROP.

A Randomized Controlled Study of Art Observation Training to Improve Medical Student Ophthalmology Skills.

Purpose: Observation and description are critical to the practice of medicine, and to ophthalmology in particular. However, medical education does not provide explicit training in these areas, and medical students are often criticized for deficiencies in these skills. We sought to evaluate the effects of formal observation training in the visual arts on the general and ophthalmologic observational skills of medical students.

Inhibition of stress-inducible HSP70 impairs mitochondrial proteostasis and function.

Protein quality control is an important component of survival for all cells. The use of proteasome inhibitors for cancer therapy derives from the fact that tumor cells generally exhibit greater levels of proteotoxic stress than do normal cells, and thus cancer cells tend to be more sensitive to proteasome inhibition. However, this approach has been limited in some cases by toxicity to normal cells.

Brain morphometric analysis predicts decline of intelligence quotient in children with sickle cell disease: A preliminary study.

Purpose: For children with sickle cell disease (SCD) and at low risk category of stroke, we aim to build a predictive model to differentiate those with decline of intelligence-quotient (IQ) from counterparts without decline, based on structural magnetic-resonance (MR) imaging volumetric analysis.

Materials And Methods: This preliminary prospective cohort study included 25 children with SCD, homozygous for hemoglobin S, with no history of stroke and transcranial Doppler mean velocities below 170cm/s at baseline. We administered the Kaufman Brief Intelligence Test (K-BIT) to each child at yearly intervals for 2-4 years.

Gunner Goggles: Implementing Augmented Reality into Medical Education.

There is evidence that both smartphone and tablet integration into medical education has been lacking. At the same time, there is a niche for augmented reality (AR) to improve this process through the enhancement of textbook learning. Gunner Goggles is an attempt to enhance textbook learning in shelf exam preparatory review with augmented reality.

Dynamic structural flexibility of α-synuclein.

α-Synuclein is a conserved, abundantly expressed protein that is partially localized in pre-synaptic terminals in the central nervous system. The precise biological function(s) and structure of α-synuclein are under investigation. Recently, the native conformation and the presence of naturally occurring multimeric assemblies have come under debate.

Microarray data reveal relationship between Jag1 and Ddr1 in mouse liver.

Alagille syndrome is an autosomal dominant disorder involving bile duct paucity and cholestasis in addition to cardiac, skeletal, ophthalmologic, renal and vascular manifestations. Mutations in JAG1, encoding a ligand in the Notch signaling pathway, are found in 95% of patients meeting clinical criteria for Alagille syndrome. In order to define the role of Jag1 in the bile duct developmental abnormalities seen in ALGS, we previously created a Jag1 conditional knockout mouse model.

Realizing the promise and importance of performance-based assessment.

Work-based assessment (WBA) is the assessment of trainees and physicians across the educational continuum of day-to-day competencies and practices in authentic, clinical environments. What distinguishes WBA from other assessment modalities is that it enables the evaluation of performance in context. In this perspective, we describe the growing importance, relevance, and evolution of WBA as it relates to competency-based medical education, supervision, and entrustment.

Regulation of protein function and signaling by reversible cysteine S-nitrosylation.

NO is a versatile free radical that mediates numerous biological functions within every major organ system. A molecular pathway by which NO accomplishes functional diversity is the selective modification of protein cysteine residues to form S-nitrosocysteine. This post-translational modification, S-nitrosylation, impacts protein function, stability, and location.

Nitric oxide regulates mitochondrial fatty acid metabolism through reversible protein S-nitrosylation.

Cysteine S-nitrosylation is a posttranslational modification by which nitric oxide regulates protein function and signaling. Studies of individual proteins have elucidated specific functional roles for S-nitrosylation, but knowledge of the extent of endogenous S-nitrosylation, the sites that are nitrosylated, and the regulatory consequences of S-nitrosylation remains limited. We used mass spectrometry-based methodologies to identify 1011 S-nitrosocysteine residues in 647 proteins in various mouse tissues.