Unique territorial and compartmental organization of chromosomes in the holocentric silkmoth.

The hallmarks of chromosome organization in multicellular eukaryotes are chromosome territories (CT), chromatin compartments, and insulated domains, including topologically associated domains (TADs). Yet, most of these elements of chromosome organization are derived from analyses of a limited set of model organisms, while large eukaryotic groups, including insects, remain mostly unexplored. Here we combine Hi-C, biophysical modeling, and microscopy to characterize the 3D genome architecture of the silkmoth, Bombyx mori. In contrast to other eukaryotes, B. mori chromosomes form highly separated territories. Similar to other eukaryotes, B. mori chromosomes segregate into active A and inactive B compartments, yet unlike in vertebrate systems, contacts between euchromatic A regions appear to be a strong driver of compartmentalization. Remarkably, we also identify a third compartment, called secluded "S," with a unique contact pattern. Each S region shows prominent short-range self-contacts and is remarkably devoid of contacts with the rest of the chromosome, including other S regions. Compartment S hosts a unique combination of genetic and epigenetic features, localizes towards the periphery of CTs, and shows developmental plasticity. Biophysical modeling reveals that the formation of such secluded domains requires highly localized loop extrusion within them, along with a low level of extrusion in A and B. Our Hi-C data supports predicted genome-wide and localized extrusion. Such a broad, non-uniform distribution of extruders has not been seen in other organisms. Overall, our analyses support loop extrusion in insects and highlight the evolutionary plasticity of 3D genome organization, driven by a new combination of known processes.

Unique territorial and sub-chromosomal organization revealed in the holocentric moth Bombyx mori.

The hallmarks of chromosome organization in multicellular eukaryotes are chromosome territories (CT), chromatin compartments, and different types of domains, including topologically associated domains (TADs). Yet, most of these concepts derive from analyses of organisms with monocentric chromosomes. Here we describe the 3D genome architecture of an organism with holocentric chromosomes, the silkworm Bombyx mori . At the genome-wide scale, B. mori chromosomes form highly separated territories and lack substantial trans contacts. As described in other eukaryotes, B. mori chromosomes segregate into an active A and an inactive B compartment. Remarkably, we also identify a third compartment, Secluded "S", with a unique contact pattern. Compartment S shows strong enrichment of short-range contacts and depletion of long-range contacts. It hosts a unique combination of genetic and epigenetic features, localizes at the periphery of CTs and shows developmental plasticity. Biophysical modeling shows that formation of such secluded domains requires a new mechanism - a high density of extruded loops within them along with low level of extrusion and compartmentalization of A and B. Together with other evidence of loop extrusion in interphase, this suggests SMC-mediated loop extrusion in this insect. Overall, our analyses highlight the evolutionary plasticity of 3D genome organization driven by a new combination of known processes.

Boost-HiC: computational enhancement of long-range contacts in chromosomal contact maps.

MOTIVATION: Genome-wide chromosomal contact maps are widely used to uncover the 3D organization of genomes. They rely on collecting millions of contacting pairs of genomic loci. Contacts at short range are usually well measured in experiments, while there is a lot of missing information about long-range contacts. RESULTS: We propose to use the sparse information contained in raw contact maps to infer high-confidence contact counts between all pairs of loci. Our algorithmic procedure, Boost-HiC, enables the detection of Hi-C patterns such as chromosomal compartments at a resolution that would be otherwise only attainable by sequencing a hundred times deeper the experimental Hi-C library. Boost-HiC can also be used to compare contact maps at an improved resolution. AVAILABILITY AND IMPLEMENTATION: Boost-HiC is available at https://github.com/LeopoldC/Boost-HiC. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Improving docking results via reranking of ensembles of ligand poses in multiple X-ray protein conformations with MM-GBSA.

There is a tendency in the literature to be critical of scoring functions when docking programs perform poorly. The assumption is that existing scoring functions need to be enhanced or new ones developed in order to improve the performance of docking programs for tasks such as pose prediction and virtual screening. However, failures can result from either sampling or scoring (or a combination of the two), although less emphasis tends to be given to the former. In this work, we use the programs GOLD and Glide on a high-quality data set to explore whether failures in pose prediction and binding affinity estimation can be attributable more to sampling or scoring. We show that identification of the correct pose (docking power) can be improved by incorporating ligand strain into the scoring function or rescoring an ensemble of diverse docking poses with MM-GBSA in a postprocessing step. We explore the use of nondefault docking settings and find that enhancing ligand sampling also improves docking power, again suggesting that sampling is more limiting than scoring for the docking programs investigated in this work. In cross-docking calculations (docking a ligand to a noncognate receptor structure) we observe a significant reduction in the accuracy of pose ranking, as expected and has been reported by others; however, we demonstrate that these alternate poses may in fact be more complementary between the ligand and the rigid receptor conformation, emphasizing that treating the receptor rigidly is an artificial constraint on the docking problem. We simulate protein flexibility by the use of multiple crystallographic conformations of a protein and demonstrate that docking results can be improved with this level of protein sampling. This work indicates the need for better sampling in docking programs, especially for the receptor. This study also highlights the variable descriptive value of RMSD as the sole arbiter of pose replication quality. It is shown that ligand poses within 2 Å of the crystallographic one can show dramatic differences in calculated relative protein-ligand energies. MM-GBSA rescoring of distinct poses overcomes some of the sensitivities of pose ranking experienced by the docking scoring functions due to protein preparation and binding site definition.

[Patient dose: implementation of a clinical practice assessment in medical imaging]. / La dosimétrie patient: exemple d'une démarche d'évaluation des pratiques en imagerie médicale.

PURPOSE: To describe our experience with the implementation of a clinical practice assessment (CPA) with regards to radiation exposure in CT. METHODS: Such a CPA requires that a reference level be available (DRL: diagnostic reference level) along with exposure data (CTDIvol and DLP) allowing for the evaluation of current practices, development of an action plan for improvement and future follow-up after implementation. RESULTS: The action plan for improvements was elaborated based on the review of 641 radiation exposure data points collected over 1 year (CTDIvol and DLP). These data were compared to DRL values of corresponding anatomical regions. The implementation of dose guidelines enabled continuous quality improvement as opposed to punctual radiation dose assessments. CONCLUSION: The requirement of recording patient exposure was an excellent opportunity to perform a CPA activity as described by the Haute Autorité de Santé (HAS) in its clinical audit process.

[Place of the radiation safety officer in the implementation of the ALARA principle through European directive 97-43 items]. / 6ôle de la personne compétente dans la sensibilisation au principe ALARA a travers l'application de la directive européenne 97-43.

The purpose of this article is to define the role of the radiation safety officer in raising the awareness of the radiology staff to the ALARA (As low as reasonable achievable) principle specified in European directive 97-43. The actions taken and the techniques used in our hospital, as well as the potential improvements that could be achieved with extra funding, will be presented. The didactic value of flow charts recording technical factors and fluoroscopy times for quality improvement will be demonstrated. In the future, a dosimeter incorporated on the new equipment could allow direct recording of the dose. The different items presented in this paper should allow routine implementation of the required elements described in the law 2003-270, i.e the French translation of European Directive 97-43.

[Sarcomatoid carcinoma of the bladder with major osseous metaplasia]. / Carcinome sarcomatoïde de la vessie avec métaplasie osseuse majeure.

The authors describe a case of sarcomatoid carcinoma of the bladder, in which the stroma presented marked calcified bone metaplasia. Mechanical lithotripsy of the tumor was necessary to allow transurethral resection.

[Pseudotumoral xanthogranulomatous pyelonephritis. A propos of 2 cases]. / Pyélonéphrite xanthogranulomateuse pseudotumorale. A propos de deux cas.

We report two cases of xanthogranulomatous pyelonephritis observed in elderly women. Diagnosis before surgery is difficult. CT is the best single examination.

[Ureteral stenosis caused by pelvic actinomycosis]. / Sténose urétérale par actinomycose pelvienne.

The authors report a case of pelvic actinomycosis causing ureteral obstruction in a 30-year-old woman. An intra-uterine device being in place for 6 years is considered as the main cause. The treatment, which included a laparotomy for abscess drainage, an indwelling double pigtail ureteral stent and a 9 month antibiotherapy led to recovery after an initial relapse.

[Colonic adenocarcinoma after Coffey's operation. A case]. / Adénocarcinome colique après intervention de Coffey. Un cas.

The authors describe a case of colonic adenocarcinoma in an 41-year-old woman who had undergone at age 3 an uretero-colic anastomosis because of bladder exstrophy. The tumor looked like an ovarian tumor and histology confirmed it was a Krûckenberg tumor of colonic origin. The authors review literature and insist on the necessity of a life long endoscopic follow-up of uretero-colic anastomosis.

[Choledochal cyst]. / Un kyste du cholédoque.

The persistence of recurrent abdominal pains in a 6 year-old girl without medical history lead to an ultrasonography being performed that showed a liquid formation, assigned to a dilated biliary duct. An oral cholecystography showed that this formation corresponded to a voluminous choledochal cyst. Surgical treatment consisted of a cyst excision with an hepatico-jejunostomy as biliary drainage.

[Calcification of the hip (circumscribed myositis ossificans of the tendon of the anterior rectus femoris)]. / Une calcification du toit du cotyle (myosite ossifiante circonscrite du tendon du droit antérieur de la cuisse).

For a young boy, without antecedent, the discovery of a calcification from the upper side of the hip is reported to an injury with extension of the thigh, six months before. The radiologic characteristics of the picture bring to the diagnostic of myositis circumscripta of the anterior muscle, which is confirmed by biopsy.