Cytogenetic bands and sharp peaks of Alu underlie large-scale segmental regulation of nuclear genome architecture.

Cytogenetic bands reflect genomic organization in large blocks of DNA with similar properties. Because banding patterns are invariant, this organization may often be assumed unimportant for genome regulation. Results here challenge that view.

Differences in Alu vs L1-rich chromosome bands underpin architectural reorganization of the inactive-X chromosome and SAHFs.

The linear DNA sequence of mammalian chromosomes is organized in large blocks of DNA with similar sequence properties, producing a pattern of dark and light staining bands on mitotic chromosomes. Cytogenetic banding is essentially invariant between people and cell-types and thus may be assumed unrelated to genome regulation. We investigate whether large blocks of Alu-rich R-bands and L1-rich G-bands provide a framework upon which functional genome architecture is built.

ZNF146/OZF and ZNF507 target LINE-1 sequences.

Repetitive sequences including transposable elements and transposon-derived fragments account for nearly half of the human genome. While transposition-competent transposable elements must be repressed to maintain genomic stability, mutated and fragmented transposable elements comprising the bulk of repetitive sequences can also contribute to regulation of host gene expression and broader genome organization. Here, we analyzed published ChIP-seq data sets to identify proteins broadly enriched on transposable elements in the human genome.

Pediatric Hospitalist Resuscitation Skills Refresher Training With Pauses for Deliberate Practice.

Introduction Pediatric hospitalists are expected to lead resuscitative efforts for cardiopulmonary arrests, but the infrequency of these events and pediatric advanced life support (PALS) re-certifications are insufficient to maintain skill proficiency.We created a novel resuscitation refresher curriculum for pediatric hospitalists with strategic pauses during simulations for expert and peer coaching of procedural skills. Methods In a tertiary care academic pediatric hospital between September 2018 to June 2019, pediatric hospitalists and fellows voluntarily participated in a series of three quarterly two-hour training sessions taught by expert peer facilitators.

SAF-A mutants disrupt chromatin structure through dominant negative effects on RNAs associated with chromatin.

Here we provide a brief review of relevant background before presenting results of our investigation into the interplay between scaffold attachment factor A (SAF-A), chromatin-associated RNAs, and DNA condensation. SAF-A, also termed heterogenous nuclear protein U (hnRNP U), is a ubiquitous nuclear scaffold protein that was implicated in XIST RNA localization to the inactive X-chromosome (Xi) but also reported to maintain open DNA packaging in euchromatin. Here we use several means to perturb SAF-A and examine potential impacts on the broad association of RNAs on euchromatin, and on chromatin compaction.

Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction.

Nuclear chromosomes transcribe far more RNA than required to encode protein. Here we investigate whether non-coding RNA broadly contributes to cytological-scale chromosome territory architecture. We develop a procedure that depletes soluble proteins, chromatin, and most nuclear RNA from the nucleus but does not delocalize XIST, a known architectural RNA, from an insoluble chromosome "scaffold.

Pediatric Thoracic Trauma Mortality in Iraq and Afghanistan Compared to the United States National Trauma Data Bank.

Introduction: The authors compared pediatric thoracic patients in the Joint Theatre Trauma Registry (JTTR) to those in the National Trauma Data Bank (NTDB) to assess differences in patient mortality rates and mortality risk accounting for age, injury patterns, and injury severity.

Materials And Methods: Patients less than 19 years of age with thoracic trauma were identified in both the JTTR and NTDB. Multiple logistic regression, χ2, Student's t-test, or Mann-Whitney U test were used as indicated to compare the two groups.

Pediatric Thoracic Trauma in Iraq and Afghanistan.

Introduction: The objective of this study is to review available data on pediatric thoracic trauma seen at U.S. military treatment facilities in Iraq and Afghanistan and describe the scope of injuries, patterns seen, and associated mortality.

Abo1, a conserved bromodomain AAA-ATPase, maintains global nucleosome occupancy and organisation.

Maintenance of the correct level and organisation of nucleosomes is crucial for genome function. Here, we uncover a role for a conserved bromodomain AAA-ATPase, Abo1, in the maintenance of nucleosome architecture in fission yeast. Cells lacking abo1(+) experience both a reduction and mis-positioning of nucleosomes at transcribed sequences in addition to increased intragenic transcription, phenotypes that are hallmarks of defective chromatin re-establishment behind RNA polymerase II.

The effects of balanced blood component resuscitation and crystalloid administration in pediatric trauma patients requiring transfusion in Afghanistan and Iraq 2002 to 2012.

Background: Component balanced resuscitation and avoidance of crystalloids in traumatically injured adults requiring massive transfusion are beneficial. Evidence for children is lacking.

Methods: After institutional review board approval was obtained, the Department of Defense Trauma Database identified 1,311 injured children 14 years or younger requiring transfusion after an injury and admitted to a deployed US military hospital from 2002 to 2012.

The Mi-2 homolog Mit1 actively positions nucleosomes within heterochromatin to suppress transcription.

Mit1 is the putative chromatin remodeling subunit of the fission yeast Snf2/histone deacetylase (HDAC) repressor complex (SHREC) and is known to repress transcription at regions of heterochromatin. However, how Mit1 modifies chromatin to silence transcription is largely unknown. Here we report that Mit1 mobilizes histone octamers in vitro and requires ATP hydrolysis and conserved chromatin tethering domains, including a previously unrecognized chromodomain, to remodel nucleosomes and silence transcription.

Should I stay or should I go? Chromodomain proteins seal the fate of heterochromatic transcripts in fission yeast.

In this issue of Molecular Cell, Ishida et al. (2012) and Keller et al. (2012) show distinct outcomes for heterochromatic RNAs that bind different chromodomain proteins; Chp1 tethers transcripts to centromeres, whereas Swi6(HP1)-bound transcripts are evicted from chromatin and destroyed.

Cdk1 phosphorylation of the kinetochore protein Nsk1 prevents error-prone chromosome segregation.

Cdk1 controls many aspects of mitotic chromosome behavior and spindle microtubule (MT) dynamics to ensure accurate chromosome segregation. In this paper, we characterize a new kinetochore substrate of fission yeast Cdk1, Nsk1, which promotes proper kinetochore-MT (k-MT) interactions and chromosome movements in a phosphoregulated manner. Cdk1 phosphorylation of Nsk1 antagonizes Nsk1 kinetochore and spindle localization during early mitosis.

RITS-connecting transcription, RNA interference, and heterochromatin assembly in fission yeast.

In recent years, a bevy of evidence has been unearthed indicating that 'silent' heterochromatin is not as transcriptionally inert as once thought. In the unicellular yeast Schizosaccharomyces pombe, the processing of transcripts derived from centromeric repeats into homologous short interfering RNA (siRNA) is essential for the formation of centromeric heterochromatin. Deletion of genes required for siRNA biogenesis showed that core components of the canonical RNA interference (RNAi) pathway are essential for centromeric heterochromatin assembly as well as for centromere function.

Continuous requirement for the Clr4 complex but not RNAi for centromeric heterochromatin assembly in fission yeast harboring a disrupted RITS complex.

Formation of centromeric heterochromatin in fission yeast requires the combined action of chromatin modifying enzymes and small RNAs derived from centromeric transcripts. Positive feedback mechanisms that link the RNAi pathway and the Clr4/Suv39h1 histone H3K9 methyltransferase complex (Clr-C) result in requirements for H3K9 methylation for full siRNA production and for siRNA production to achieve full histone methylation. Nonetheless, it has been proposed that the Argonaute protein, Ago1, is the key initial trigger for heterochromatin assembly via its association with Dicer-independent "priRNAs.

Pediatric wartime admissions to US military combat support hospitals in Afghanistan and Iraq: learning from the first 2,000 admissions.

Background: Humanitarian and civilian emergency care accounts for up to one-third of US military combat support hospital (CSH) admissions. Almost half of these admissions are children. The purpose of this study is to describe the features of pediatric wartime admissions to deployed CSHs in Iraq and Afghanistan.

The U.S. military wartime pediatric trauma mission: how surgeons and pediatricians are adapting the system to address the need.

Purpose: Over 3,500 infants and children, many critically ill and injured, have been admitted to military combat support hospitals (CSH) in Afghanistan and Iraq, which are not doctrinally staffed or equipped to provide their care. This report details how the military medical system is adapting to create a data driven and comprehensive response to optimize the medical and surgical pediatric care being provided.

Methods: Information from multiple sources was used over time to craft the military medical response to the pediatric wartime mission.

Mediastinal Kaposiform hemangioendothelioma and Kasabach-Merritt phenomenon in an infant: treatment with interferon.

A 2-week-old infant developed respiratory failure due to a mediastinal Kaposiform hemangioendothelioma that was complicated by thrombocytopenia and consumptive coagulopathy. Initial surgery was unsuccessful at removing the tumorous infiltration of mediastinal structures. Multiple transfusions with fresh frozen plasma, platelets, and red blood cells were needed for the consumptive coagulopathy, and ventilatory support was required for 5 months.

Clinical utility of the bispectral index score when compared to the University of Michigan Sedation Scale in assessing the depth of outpatient pediatric sedation.

This single blinded observational study compared the bispectral index (BIS) monitor with a validated pediatric sedation scale, the University of Michigan Sedation Scale (UMSS), to evaluate whether the BIS score can be used to judge the depth of sedation in pediatric outpatients. Thirty-eight children, with a mean age of 5.8 years, undergoing routine sedation for both noninvasive and gastrointestinal procedures, had simultaneous BIS and UMSS scores recorded.

Sleep deprivation for pediatric sedated procedures: not worth the effort.

Objective: Sleep deprivation is commonly used to enhance the effectiveness of pediatric sedation and to decrease sedation failures. We reviewed our sedation database to evaluate the efficacy of sleep deprivation.

Methods: The entire pediatric sedation unit database (n = 5640) was reviewed retrospectively.

Tolerance of family presence during pediatric cardiopulmonary resuscitation: a snapshot of military and civilian pediatricians, nurses, and residents.

Background: Family presence during cardiopulmonary resuscitation is becoming a more common and accepted practice.

Objectives: We wanted to determine the views held by pediatricians on family presence during pediatric cardiopulmonary resuscitation. We hypothesized that physicians who had more experience with critical illness and death would be more willing to allow parental presence.