Molecular refinement of gibbon genome rearrangements

The gibbon karyotype is known to be extensively rearranged when compared to the human and to the ancestral primate karyotype. By combining a bioinformatics (paired-end sequence analysis) approach and a molecular cytogenetics approach, we have refined the synteny block arrangement of the white-cheeked gibbon (Nomascus leucogenys, NLE) with respect to the human genome. We provide the first detailed clone framework map of the gibbon genome and refine the location of 86 evolutionary breakpoints to <1 Mb resolution. An additional 12 breakpoints, mapping primarily to centromeric and telomeric regions, were mapped to approximately 5 Mb resolution. Our combined FISH and BES analysis indicates that we have effectively subcloned 49 of these breakpoints within NLE gibbon BAC clones, mapped to a median resolution of 79.7 kb. Interestingly, many of the intervals associated with translocations were gene-rich, including some genes associated with normal skeletal development. Comparisons of NLE breakpoints with those of other gibbon species reveal variability in the position, suggesting that chromosomal rearrangement has been a longstanding property of this particular ape lineage. Our data emphasize the synergistic effect of combining computational genomics and cytogenetics and provide a framework for ultimate sequence and assembly of the gibbon genome.     

Evolutionary descent of a human chromosome 6 neocentromere: A jump back to 17 million years ago

Molecular cytogenetics provides a visual, pictorial record of the tree of life, and in this respect the fusion origin of human chromosome 2 is a well-known paradigmatic example. Here we report on a variant chromosome 6 in which the centromere jumped to 6p22.1. ChIP-chip experiments with antibodies against the centromeric proteins CENP-A and CENP-C exactly defined the neocentromere as lying at chr6:26,407–26,491 kb. We investigated in detail the evolutionary history of chromosome 6 in primates and found that the primate ancestor had a homologous chromosome with the same marker order, but with the centromere located at 6p22.1. Sometime between 17 and 23 million years ago (Mya), in the common ancestor of humans and apes, the centromere of chromosome 6 moved from 6p22.1 to its current location. The neocentromere we discovered, consequently, has jumped back to the ancestral position, where a latent centromere-forming potentiality persisted for at least 17 Myr. Because all living organisms form a tree of life, as first conceived by Darwin, evolutionary perspectives can provide compelling underlying explicative grounds for contemporary genomic phenomena.One of the major tenets of Darwin''s theory of evolution is that all forms of life are connected by descent from common ancestors. Extant species represent the endpoint of branches on the tree of life. Paleontology, comparative anatomy, embryology, and more recently comparative genomics, drew trees in which, as in a million-pieces puzzle, each species was placed into a particular position. Bioinformatic sequence comparisons, which can evaluate billions of characters, are robust in scientific terms, but not very accessible to the general public. The molecular cytogenetic approach to the tree of life is more adapt for public viewing because it provides images “that speak.” The most renowned example in this respect is the fusion of two hominid ancestral chromosomes that generated human chromosome 2 and reduced the total number of human chromosomes from 48 found in great apes to 46 (Yunis and Prakash 1982).Between 17 and 23 million yeas ago (Mya) the centromere of chromosome 6 repositioned to its current location in a common ancestor of the Hominoids (lesser apes [gibbon and siamang], great apes [orangutan, gorilla, and chimpanzee], and humans). Its original position corresponded to human 6p22.1, which (we show here) is the ancestral centromere location for primates. In this report we demonstrate that a human variant chromosome 6, segregating in a three-generational family of normal individuals, has a centromere that repositioned back to the ancestral primate location. Knowledge of the evolutionary past provides compelling underlying explicative grounds for contemporary genomic phenomena.     

Improved reproducibility of right ventricular volumes and function estimation from cardiac magnetic resonance images using level-set models.

This study aims to assess whether an alternative method, that is based on volumetric surface detection (VoSD) without tracing and is totally free of geometric assumptions, can improve the reproducibility of right ventricular (RV) volume quantification from cardiac magnetic resonance (CMR) images, in comparison with a conventional disk-area technique. In a sample of 23 patients, with wide variability of RV end-diastolic volume (EDV: 47-131 ml), end-systolic volume (ESV: 20-76 ml), and ejection fraction (EF: 29-73%), using the standard method (Argus, Siemens) as the reference, the VoSD method showed good agreement for EDV, ESV, and EF estimations (correlation coefficient: 0.91, 0.94, and 0.94; Bland-Altman biases: 1 ml, 1 ml, and 0%; limits of agreement: +/-16 ml, +/-11 ml, and +/-11%, respectively). An analysis of the reproducibility of the two methods showed lower intraobserver variability for the VoSD method than for the conventional method, as evidenced by the coefficient of variability (CoV) values (2-6% vs. 8-15%; P < 0.05). In addition, the VoSD method showed improved interobserver reproducibility (7-10% vs. 8-15%), but the difference was statistically significant only for EF estimation variability (8 vs. 15%, P < 0.05). In conclusion, the newly developed VoSD technique allows accurate measurements of RV volumes and function, and appears to be more reproducible than the conventional methodology.     

Hysteroscopic Removal of Gauze Packing Inadvertently Sutured to the Uterine Cavity: Report of 2 Cases

We report on 2 cases of successful hysteroscopic removal of uterovaginal packing, inserted during cesarean sections after uterine hemorrhage resistant to medical therapy. The packing, in both cases, could not be removed vaginally with sponge forceps because the packing had been sutured to the uterine cavity. A hysteroscopic approach enabled identification and cutting with 5F scissors of the stitches fixing the packing to the uterine walls, allowing straightforward removal in an outpatient setting and avoiding a repeated laparotomy. Some useful techniques to handle such a situation are described.     

What does 'diagnostic hysteroscopy' mean today? The role of the new techniques

PURPOSE OF REVIEW: Visual examination of the uterine cavity and contextual operative facilities have provided the gynecologist with the perfect 'diagnostic' tool, making it possible to examine the cavity and biopsy suspected areas under direct visualization. RECENT FINDINGS: The approach used to insert the scope, together with the diameter of the hysteroscope and the distention of the uterine cavity, are of extreme importance in reducing patient discomfort to a minimum during an outpatient examination. The vaginoscopic approach (without speculum or tenaculum) has definitively eliminated patient discomfort related to the traditional approach to the uterus. One of the major problems for endoscopists is passing through the internal cervical os; the new generation of hysteroscopes, with an oval profile and a total diameter between 4 and 5 mm, are strictly correlated to the anatomy of the cervical canal. Miniaturized instruments have enabled the physician not only to perform targeted hysteroscopic biopsies, but also to treat benign intrauterine pathologies, such as polyps and sinechiae, without any premedication or anesthesia. This has been defined as a 'see & treat' procedure: there is no longer a distinction between the diagnostic and operative procedures, but a single procedure in which the operative part is perfectly integrated in the diagnostic work-up. SUMMARY: Diagnostic hysteroscopy has long paid the price of being a purely visual method of investigation. Today, thanks to recent advances in instrumentation and to modified techniques related to the simultaneous use of the scope and of instruments, hysteroscopy is finally achieving the full accuracy that has been awaited for the last 20 years.