Large, Single Institution Review of Prognostic Factors in Oligodendroglioma

Studies have demonstrated an association between loss of heterozygosity on chromosome 1p and chromosome 19q in oligodendrogliomas with both chemosensitivity and prolonged survival. This represents the first time genetic mutations have been utilized to guide clinical decision making. Studies have also found these genetic mutations to be associated with magnetic resonance imaging (MRI) features including indistinct tumor borders on T1-weighted imaging, susceptibility effect, and mixed signal intensity. However, no study has yet demonstrated an association between imaging features and survival. We seek to confirm the clinical utility of known prognostic factors such as age and tumor grade while investigating the potential importance of imaging characteristics in predicting survival. We conducted a large, single-institution retrospective chart review of patients with tissue diagnoses of oligodendroglioma. Pathology reports, allelic status studies, MR imaging, and survival information were reviewed. Survival curves, Two-sided chi-square tests, and generalized linear models failed to reveal an association between survival and gender, age, tumor grade, allelic status, or imaging characteristics. We found no association between imaging characteristics and allelic status. The failure to confirm even well-accepted prognostic factors suggests limitations in the study largely attributable to small sample size. This limitation was due to availability of necessary information, rarity of the tumor, and only recent availability of genetic testing. Further studies with larger populations need to be conducted to fully determine the prognostic utility of MRI features

Piezoelectric and optical setup to measure an electrical field: Application to the longitudinal near-field generated by a tapered coax

We propose a new setup to measure an electrical field in one direction. This setup is made of a piezoelectric sintered lead zinconate titanate film and an optical interferometric probe. We used this setup to investigate how the shape of the extremity of a coaxial cable influences the longitudinal electrical near-field generated by it. For this application, we designed our setup to have a spatial resolution of 100 um in the direction of the electrical field. Simulations and experiments are presented

Genome information processing by the INO80 chromatin remodeler positions nucleosomes [preprint]

The fundamental molecular determinants by which ATP-dependent chromatin remodelers organize nucleosomes across eukaryotic genomes remain largely elusive. Here, chromatin reconstitutions on physiological, whole-genome templates reveal how remodelers read and translate genomic information into nucleosome positions. Using the yeast genome and the multi-subunit INO80 remodeler as a paradigm, we identify DNA shape/mechanics encoded signature motifs as sufficient for nucleosome positioning and distinct from known DNA sequence preferences of histones. INO80 processes such information through an allosteric interplay between its core- and Arp8-modules that probes mechanical properties of nucleosomal and linker DNA. At promoters, INO80 integrates this readout of DNA shape/mechanics with a readout of co-evolved sequence motifs via interaction with general regulatory factors bound to these motifs. Our findings establish a molecular mechanism for robust and yet adjustable +1 nucleosome positioning and, more generally, remodelers as information processing hubs that enable active organization and allosteric regulation of the first level of chromatin

Characteristics of Patients Lost to Follow-up after Bariatric Surgery

After bariatric surgery lifelong follow-up is recommended. Evidence of the consequences and reasons for being lost to follow-up (LTFU) is sparse. In this prospective study follow-up data of all patients who underwent bariatric surgery between 2008 and 2017 at a certified obesity centre were investigated. LTFU patients were evaluated through a structured telephone interview. Overall, 573 patients (female/male 70.9%/29.1%), aged 44.1 ± 11.2 years, preoperative BMI 52.1 ± 8.4 kg/m2 underwent bariatric surgery. Out of these, 33.2% had type 2 diabetes mellitus and 74.4% had arterial hypertension. A total of 290 patients were LTFU, of those 82.1% could be reached. Baseline characteristics of patients in follow-up (IFU) and LTFU were comparable, but men were more often LTFU (p = 0.01). Reported postoperative total weight loss (%TWL) and improvements of comorbidities were comparable, but %TWL was higher in patients remaining in follow-up for at least 2 years (p = 0.013). Travel issues were mentioned as the main reason for being LTFU. A percentage of 77.6% of patients reported to regularly supplement micronutrients, while 71.0% stated regular monitoring of their micronutrient status, mostly by primary care physicians. Despite comparable reported outcomes of LTFU to IFU patients, the duration of the in-centre follow-up period affected %TWL. There is a lack of sufficient supplementation and monitoring of micronutrients in a considerable number of LTFU patients

Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement.

Eukaryotic DNA is packaged into nucleosome arrays, which are repositioned by chromatin remodeling complexes to control DNA accessibility. The Saccharomyces cerevisiae RSC (Remodeling the Structure of Chromatin) complex, a member of the SWI/SNF chromatin remodeler family, plays critical roles in genome maintenance, transcription, and DNA repair. Here, we report cryo-electron microscopy (cryo-EM) and crosslinking mass spectrometry (CLMS) studies of yeast RSC complex and show that RSC is composed of a rigid tripartite core and two flexible lobes. The core structure is scaffolded by an asymmetric Rsc8 dimer and built with the evolutionarily conserved subunits Sfh1, Rsc6, Rsc9 and Sth1. The flexible ATPase lobe, composed of helicase subunit Sth1, Arp7, Arp9 and Rtt102, is anchored to this core by the N-terminus of Sth1. Our cryo-EM analysis of RSC bound to a nucleosome core particle shows that in addition to the expected nucleosome-Sth1 interactions, RSC engages histones and nucleosomal DNA through one arm of the core structure, composed of the Rsc8 SWIRM domains, Sfh1 and Npl6. Our findings provide structural insights into the conserved assembly process for all members of the SWI/SNF family of remodelers, and illustrate how RSC selects, engages, and remodels nucleosomes

Systematic evaluation of chromosome conformation capture assays [preprint]

Chromosome conformation capture (3C)-based assays are used to map chromatin interactions genome-wide. Quantitative analyses of chromatin interaction maps can lead to insights into the spatial organization of chromosomes and the mechanisms by which they fold. A number of protocols such as in situ Hi-C and Micro-C are now widely used and these differ in key experimental parameters including cross-linking chemistry and chromatin fragmentation strategy. To understand how the choice of experimental protocol determines the ability to detect and quantify aspects of chromosome folding we have performed a systematic evaluation of experimental parameters of 3C-based protocols. We find that different protocols capture different 3D genome features with different efficiencies. First, the use of cross-linkers such as DSG in addition to formaldehyde improves signal-to-noise allowing detection of thousands of additional loops and strengthens the compartment signal. Second, fragmenting chromatin to the level of nucleosomes using MNase allows detection of more loops. On the other hand, protocols that generate larger multi-kb fragments produce stronger compartmentalization signals. We confirmed our results for multiple cell types and cell cycle stages. We find that cell type-specific quantitative differences in chromosome folding are not detected or underestimated by some protocols. Based on these insights we developed Hi-C 3.0, a single protocol that can be used to both efficiently detect chromatin loops and to quantify compartmentalization. Finally, this study produced ultra-deeply sequenced reference interaction maps using conventional Hi-C, Micro-C and Hi-C 3.0 for commonly used cell lines in the 4D Nucleome Project