Trypanosoma cruzi mitochondrial maxicircles display species- and strain-specific variation and a conserved element in the non-coding region

BACKGROUND: The mitochondrial DNA of kinetoplastid flagellates is distinctive in the eukaryotic world due to its massive size, complex form and large sequence content. Comprised of catenated maxicircles that contain rRNA and protein-coding genes and thousands of heterogeneous minicircles encoding small guide RNAs, the kinetoplast network has evolved along with an extreme form of mRNA processing in the form of uridine insertion and deletion RNA editing. Many maxicircle-encoded mRNAs cannot be translated without this post-transcriptional sequence modification. RESULTS: We present the complete sequence and annotation of the Trypanosoma cruzi maxicircles for the CL Brener and Esmeraldo strains. Gene order is syntenic with Trypanosoma brucei and Leishmania tarentolae maxicircles. The non-coding components have strain-specific repetitive regions and a variable region that is unique for each strain with the exception of a conserved sequence element that may serve as an origin of replication, but shows no sequence identity with L. tarentolae or T. brucei. Alternative assemblies of the variable region demonstrate intra-strain heterogeneity of the maxicircle population. The extent of mRNA editing required for particular genes approximates that seen in T. brucei. Extensively edited genes were more divergent among the genera than non-edited and rRNA genes. Esmeraldo contains a unique 236-bp deletion that removes the 5'-ends of ND4 and CR4 and the intergenic region. Esmeraldo shows additional insertions and deletions outside of areas edited in other species in ND5, MURF1, and MURF2, while CL Brener has a distinct insertion in MURF2. CONCLUSION: The CL Brener and Esmeraldo maxicircles represent two of three previously defined maxicircle clades and promise utility as taxonomic markers. Restoration of the disrupted reading frames might be accomplished by strain-specific RNA editing. Elements in the non-coding region may be important for replication, transcription, and anchoring of the maxicircle within the kinetoplast network

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

Infrared Emission of Normal Galaxies from 2.5 to 12 Microns: ISO Spectra, Near-Infrared Continuum and Mid-Infrared Emission Features

We present ISO-PHOT spectra of the regions 2.5-4.9um and 5.8-11.6um for a sample of 45 disk galaxies from the U.S. ISO Key Project on Normal Galaxies. The spectra can be decomposed into three spectral components: (1) continuum emission from stellar photospheres, which dominates the near-infrared (2.5- 4.9um; NIR) spectral region; (2) a weak NIR excess continuum, which has a color temperature of ~ 1000K, carries a luminosity of a few percent of the total far-infrared luminosity L(FIR), and most likely arises from the ISM; and (3) the well-known broad emission features at 6.2, 7.7, 8.6 and 11.3 um, which are generally attributed to aromatic carbon particles. These aromatic features in emission (AFEs) dominate the mid-infrared (5.8-11.6 um; MIR) part of the spectrum, and resemble the so-called Type-A spectra observed in many non-stellar sources and the diffuse ISM in our own Galaxy. The relative strengths of the AFEs vary by 15-25% among the galaxies. However, little correlation is seen between these variations and either IRAS 60um-to-100um flux density ratio R(60/100) or the FIR-to-blue luminosity ratio L(FIR)/L(B), suggesting that the observed variations are not a direct consequence of the radiation field differences among the galaxies. We demonstrate that the NIR excess continuum and AFE emission are correlated, suggesting that they are produced by similar mechanisms and similar (or the same) material. On the other hand, as the current star-formation activity increases, the overall strengths of the AFEs and the NIR excess continuum drop significantly with respect to that of the far-infrared emission from large dust grains. This is likely a consequence of the preferential destruction in intense radiation fields of the small carriers responsible for the NIR/AFE emission.Comment: With 8 tables and 12 figures; to appear in the Astrophysical Journa