Targeted delivery of napabucasin with radiotherapy improves outcomes in diffuse midline glioma.

Background: Diffuse midline glioma (DMG) is the most aggressive primary brain tumor in children. All previous studies examining the role of systemic agents have failed to demonstrate a survival benefit; the only standard of care is radiation therapy (RT). Successful implementation of radiosensitization strategies in DMG remains an essential and promising avenue of investigation.

OGT prevents DNA demethylation and suppresses the expression of transposable elements in heterochromatin by restraining TET activity genome-wide.

The GlcNAc transferase OGT interacts robustly with all three mammalian TET methylcytosine dioxygenases. We show here that deletion of the gene in mouse embryonic stem cells (mESC) results in a widespread increase in the TET product 5-hydroxymethylcytosine (5hmC) in both euchromatic and heterochromatic compartments, with concomitant reduction of the TET substrate 5-methylcytosine (5mC) at the same genomic regions. mESC engineered to abolish the TET1-OGT interaction likewise displayed a genome-wide decrease of 5mC.

Acute deletion of TET enzymes results in aneuploidy in mouse embryonic stem cells through decreased expression of Khdc3.

TET (Ten-Eleven Translocation) dioxygenases effect DNA demethylation through successive oxidation of the methyl group of 5-methylcytosine (5mC) in DNA. In humans and in mouse models, TET loss-of-function has been linked to DNA damage, genome instability and oncogenesis. Here we show that acute deletion of all three Tet genes, after brief exposure of triple-floxed, Cre-ERT2-expressing mouse embryonic stem cells (mESC) to 4-hydroxytamoxifen, results in chromosome mis-segregation and aneuploidy; moreover, embryos lacking all three TET proteins showed striking variation in blastomere numbers and nuclear morphology at the 8-cell stage.

Tracing the Lineage of Two Traits Associated with the Coat Protein of the : Silencing Suppression and HR Elicitation in Species.

In this paper we have characterized the lineage of two traits associated with the coat proteins (CPs) of the tombusvirids: Silencing suppression and HR elicitation in species. We considered that the tombusvirid CPs might collectively be considered an effector, with the CP of each CP-encoding species comprising a structural variant within the family. Thus, a phylogenetic analysis of the CP could provide insight into the evolution of a pathogen effector.

The P1 gene of Cauliflower mosaic virus is responsible for breaking resistance in Arabidopsis thaliana ecotype Enkheim (En-2).

Arabidopsis thaliana ecotype En-2 is resistant to several strains of Cauliflower mosaic virus (CaMV), including strain W260, but is susceptible to strain NY8153. Resistance in En-2 is conditioned by a single, semi-dominant gene called CAR1. We constructed several recombinant infectious clones between W260 and NY8153 and evaluated their capability to infect En-2.

A model for intracellular movement of Cauliflower mosaic virus: the concept of the mobile virion factory.

The genomes of many plant viruses have a coding capacity limited to <10 proteins, yet it is becoming increasingly clear that individual plant virus proteins may interact with several targets in the host for establishment of infection. As new functions are uncovered for individual viral proteins, virologists have realized that the apparent simplicity of the virus genome is an illusion that belies the true impact that plant viruses have on host physiology. In this review, we discuss our evolving understanding of the function of the P6 protein of Cauliflower mosaic virus (CaMV), a process that was initiated nearly 35 years ago when the CaMV P6 protein was first described as the 'major inclusion body protein' (IB) present in infected plants.

Association of the P6 protein of Cauliflower mosaic virus with plasmodesmata and plasmodesmal proteins.

The P6 protein of Cauliflower mosaic virus (CaMV) is responsible for the formation of inclusion bodies (IBs), which are the sites for viral gene expression, replication, and virion assembly. Moreover, recent evidence indicates that ectopically expressed P6 inclusion-like bodies (I-LBs) move in association with actin microfilaments. Because CaMV virions accumulate preferentially in P6 IBs, we hypothesized that P6 IBs have a role in delivering CaMV virions to the plasmodesmata.

The P6 protein of Cauliflower mosaic virus interacts with CHUP1, a plant protein which moves chloroplasts on actin microfilaments.

The gene VI product, protein 6 (P6), of Cauliflower mosaic virus (CaMV) assembles into large, amorphous inclusion bodies (IBs) that are considered sites for viral protein synthesis and viral genome replication and encapsidation. P6 IBs align with microfilaments and require them for intracellular trafficking, a result implying that P6 IBs function to move virus complexes or virions within the cell to support virus physiology. Through a yeast two-hybrid screen we determined that CHUP1, a plant protein allowing chloroplast transport through an interaction with chloroplast and microfilament, interacts with P6.

A survey of resistance to Tomato bushy stunt virus in the genus Nicotiana reveals that the hypersensitive response is triggered by one of three different viral proteins.

In this study, we screened 22 Nicotiana spp. for resistance to the tombusviruses Tomato bushy stunt virus (TBSV), Cucumber necrosis virus, and Cymbidium ringspot virus. Eighteen species were resistant, and resistance was manifested in at least two different categories.

Pyloromyotomy: randomized control trial of laparoscopic vs open technique.

Purpose: Open pyloromyotomy remains as the criterion standard treatment for hypertrophic pyloric stenosis with the laparoscopic approach rapidly gaining adoption. We present a prospective, randomized trial between the 2 approaches.

Methods: After institutional review board approval, 98 patients with hypertrophic pyloric stenosis were consecutively randomized to either open or laparoscopic pyloromyotomy.

A mathematical model to predict length of stay in pediatric ATV accident victims.

Background: Children under age 12 y represent 15% of all-terrain vehicle (ATV)-related deaths, and those under 16 y old represent >36% of deaths nationwide. In recent years, this has accounted for an increasing proportion of pediatric trauma victims and longer hospitalizations secondary to worsened injuries. We believe it is possible to create a simple mathematical model that can be used to predict hospital length of stay.

Comparative analysis of the capacity of tombusvirus P22 and P19 proteins to function as avirulence determinants in Nicotiana species.

We have used an agroinfiltration assay for a comparative study of the roles of tombusvirus P22 and P19 proteins in elicitation of hypersensitive response (HR)-like necrosis and the role of P19 in silencing suppression in Nicotiana species. The advantage of agroinfiltration rather than expression in plant virus vectors is that putative viral avirulence proteins can be evaluated in isolation, eliminating the possibility of synergistic effects with other viral proteins. We found that tombusvirus P22 and P19 proteins elicited HR-like necrosis in certain Nicotiana species but, also, that Nicotiana species could recognize subtle differences in sequence between these proteins.

Human mitochondrial oxidative capacity is acutely impaired after burn trauma.

Background: Mitochondrial proteins and genes are damaged after burn injury in animals and are assessed in human burn patients in this study.

Methods: The rates of maximal muscle mitochondrial oxidative capacity (adenosine triphosphate production) and uncoupled oxidation (heat production) for both palmitate and pyruvate were measured in muscle biopsies from 40 children sustaining burns on more than 40% of their body surface area and from 13 healthy children controls.

Results: Maximal mitochondrial oxidation of pyruvate and palmitate were reduced in burn patients compared with controls (4.

Insulin sensitivity is related to fat oxidation and protein kinase C activity in children with acute burn injury.

Impaired fatty acid oxidation occurs with type 2 diabetes and is associated with accumulations of intracellular lipids, which may increase diacylglycerol (DAG), stimulate protein kinase C activity, and inactivate insulin signaling. Glucose and fat metabolism are altered in burn patients, but have never been related to intracellular lipids or insulin signaling. Thirty children sustaining >40% total body surface area burns were studied acutely with glucose and palmitate tracer infusions and a hyper-insulinemic euglycemic clamp.

Silencing of the N family of resistance genes in Nicotiana edwardsonii compromises the hypersensitive response to tombusviruses.

The nontarget effects associated with silencing of the N gene in Nicotiana edwardsonii, an amphidiploid species derived from N. glutinosa and N. clevelandii, have been characterized in this study.

Outcome of gastroschisis: a 20-year case review of infants with gastroschisis born in Galveston, Texas.

Background/purpose: In the past decade, the preferred method of closure of gastroschisis at our institution has been staged reduction using a silo with repair on an elective basis (SR) rather than primary surgical closure (PC). We performed a 20-year case review of infants with gastroschisis at a university hospital to compare these shifts in management and to determine factors affecting outcome.

Methods: Seventy-two cases were reviewed from 1983 to 2003.

Imaging of acute appendicitis: US as the primary imaging modality.

Background: The investigation of the acute abdomen in infants and children has evolved during the last two decades, placing imagers at the forefront of the evaluation and diagnosis of acute right lower quadrant abdominal problems. US and CT have recently been shown to be equally accurate in the diagnosis of acute appendicitis, but not everyone agrees.

Objective: To demonstrate the efficacy of triaging patients with acute abdominal problems that suggest appendicitis with US as the primary imaging modality.

Intestinal zygomycosis due to Absidia corymbifera mimicking necrotizing enterocolitis in a preterm neonate.

Zygomycosis is a rare fungal disease that occurs in compromised human hosts, including the preterm infant. The three clinical forms of zygomycosis are cellulitis, disseminated, and gastrointestinal, and the last often mimics necrotizing enterocolitis (NEC), complicating the diagnosis. This report details a case of primary gastrointestinal zygomycosis due to Absidia corymbifera, mimicking NEC, in a preterm infant, and emphasizes features that may lead to earlier diagnosis and treatment of future cases.

Severe ciprofloxacin-associated pseudomembranous colitis in an eight-year-old child.

Clostridium difficile is the principal cause of antibiotic-associated diarrhea and pseudomembranous enterocolitis in children. A case of severe pseudomembranous colitis developing in an 8-year-old child who had received oral ciprofloxacin therapy as part of an investigational protocol is presented. The safety and efficacy of fluoroquinolones in children has not yet been established.

Validity of plain films in intussusception.

The aim of this study was to re-evaluate the specificity of plain film findings in intussusception. The plain film findings in 80 cases of proven intussusception were reviewed. Findings documented were: (1) presence or absence of small bowel obstruction, (2) paucity of right lower quadrant gas, (3) presence of an intracolonic mass, (4) presence of a rim or target sign, and (5) presence of the classic triad of intestinal obstruction, intracolonic mass, and paucity of right lower quadrant gas.

Meconium obstruction in the very low birth weight premature infant.

Meconium obstruction of prematurity is a distinct clinical condition that occurs in very low birth weight infants, predisposing them to intestinal perforation and a prolonged hospitalization if not diagnosed and treated promptly. We report a series of 21 infants, including 2 detailed case reports, whose clinical course is indicative of meconium obstruction of prematurity. Specific risk factors are identified along with descriptions of clinical and radiologic findings, disease course, treatment, and outcome.

Genital and perineal burns in children: 10 years of experience at a major burn center.

Purpose: The aim of this report is to review a decade of experience in the management of perineal and genital burns at a major burn center.

Methods: Seventy-eight children who sustained perineal or genital burns admitted to the Shriners Hospitals for Children in Galveston are discussed.

Results: Genital and perineal burns occurred in the context of major burns and were rarely isolated.