How to dissect the pelvic nerves: from microanatomy to surgical rules. An evidence-based clinical review.

Background: Advanced gynaecological procedures often include extensive pelvic dissections, with the nervous structures involved in the disease. Nerve-sparing and preservation is a key factor in reducing postoperative morbidity. Objectives: The goal of this review is to describe in detail the structure of the pelvic nerves and to gather information from other surgical specialties to give recommendations for safe nerve dissection applied in different gynaecological subspecialties. Materials and Methods: An extensive literature review was carried out in PubMed and Google Scholar. The search included articles concerning peripheral nerve anatomy, mechanisms of injury and different dissection techniques, with the most exhaustive being analysed for the review. Articles from different fields of medicine like orthopaedics, plastic surgery, maxillofacial surgery dealing with peripheral nerve injuries and repair have been reviewed. Results: The following review demonstrates the in-depth anatomy and mechanism of injury of the peripheral nerves, describes the different techniques for neurolysis and proposes some directions for safe nerve dissection. Conclusion: When performing complex gynaecological surgeries, the surgeon should avoid unnecessary nerve handling, apply nerve-sparing techniques whenever possible and use the new devices to preserve the nervous structures. Advanced gynaecological surgeries should be performed in specialised centres by expert surgeons with comprehensive knowledge in neuropelveology. What is new?: To our knowledge, this is the first article focused on peripheral nerves that collects data from such a wide range of specialties in order to propose the most comprehensive recommendations that could be applied in pelvic surgery.

Protein refolding versus aggregation: computer simulations on an intermediate-resolution protein model.

Computer simulations are performed on a system of eight model peptide chains to study how the competition between protein refolding and aggregation affects the optimal conditions for refolding of four-helix bundles. The discontinuous molecular dynamics algorithm is utilized along with an intermediate-resolution protein model that we developed for this work. Physically, the model is much more detailed than any model used to date for simulations of protein aggregation. Each model residue consists of a detailed, three-bead backbone and a simplified, single-bead side-chain. Excluded volume, hydrogen bond, and hydrophobic interactions are modeled with discontinuous (i.e. hard-sphere and square-well) potentials. Simulations efficiently sample conformational space, and complete folding trajectories from random initial configurations to two four-helix bundles are possible within two days on a single processor workstation. Folding of the bundles follows two main pathways, one through a trimeric intermediate and the other through an intermediate with two dimers. The proportion of trajectories that follow each route is significantly different for the eight-peptide system in this work than in a previously studied four-peptide system, which yields one four-helix bundle, suggesting, as our previous simulations have, that protein folding properties are strongly influenced by the presence of other proteins. Folding of the bundles is optimal within a fixed temperature range, with the high-temperature boundary a function of the complexity of the protein (or oligomer) to be folded and the low-temperature boundary a function of the complexity of the protein's environment. Above the optimal temperature range for folding, the model chains tend to unfold; below the optimal range, the model chains tend to aggregate. As has been seen previously, aggregates have substantial levels of native secondary structure, suggesting that aggregates are composed largely of partially folded intermediates, not denatured chains.

Assembly of a tetrameric alpha-helical bundle: computer simulations on an intermediate-resolution protein model.

Discontinuous molecular dynamics (DMD) simulation on an intermediate-resolution protein model is used to study the folding of an isolated, small model peptide to an amphipathic alpha-helix and the assembly of four of these model peptides into a four-helix bundle. A total of 129 simulations were performed on the isolated peptide, and 50 simulations were performed on the four-peptide system. Simulations efficiently sample conformational space allowing complete folding trajectories from random initial configurations to be observed within 15 min for the one-peptide system and within 15 h for the four-peptide system on a 500-MHz workstation. The native structures of both the alpha-helix and the four-helix bundle are consistent with experimental characterization studies and with results from previous simulations on these model peptides. In both the one- and four-peptide systems, the native state is achieved during simulations within an optimal temperature range, a phenomenon also observed experimentally. The ease with which our simulations yield reasonable estimates of folded structures demonstrates the power of the intermediate-resolution model developed for this work and the DMD algorithm and suggests that simulations of very long times and of multiprotein systems may be possible with this model.

The regulation of the cell cycle during Drosophila embryogenesis: the transition to polyteny.

The process of polytenization plays a crucial role in Drosophila development, and most of the larval tissues are polytene. By analyzing the pattern of DNA replication in embryos pulse-labeled with BrdU, we show that many larval tissues undergo a transition to begin becoming polytene late in embryogenesis. Our results demonstrate that in these larval tissues polyteny results from a modified cell cycle, the endo cell cycle, in which there is only an S (synthesis) phase and a G (gap) phase. A key regulator of the mitotic cell cycle, the product of the string gene (the Drosophila homologue of cdc25), is not required for the endo cell cycle. The developmental regulation of the endo cell cycle is striking in that tissue-specific domains undergo polytene DNA replication in a dynamic pattern at defined times in embryogenesis. During subsequent rounds of the endo cell cycle in late embryogenesis and first instar larval development, the domains are subdivided and the temporal control is not as rigid. The length of the G phase varies among different tissues. By quantifying DNA content, we show that during the early polytene S phases the genome is not fully duplicated.

Changes in gene expression induced by a phorbol diester: expression of IL 2 receptor, T3, and T cell antigen receptor.

Phorbol esters cause an apparent differentiation of human T leukemic cell lines. It was shown previously that TPA induces the expression of the interleukin 2 (IL 2) receptor and the T3 complex on some T cell lines, including CCRF-CEM. We demonstrate that expression of the IL 2 receptor correlated with an induction of the 3.5 and 1.5 kb IL 2 receptor mRNA. In addition, the TPA-induced expression of the T3 polypeptides was found to be accompanied by induction of a putative T cell antigen receptor heterodimer on CEM cells. This was demonstrated by the co-precipitation of the T cell receptor with T3 from digitonin-solubilized cells. The cells expressed high levels of T3 delta- and T cell receptor beta-chain mRNA in the absence of TPA. The effect of TPA was to cause a rapid accumulation of T cell receptor alpha-chain mRNA. This suggested that the alpha-chain gene was rearranged before TPA induction and that expression of the T cell receptor/T3 complex on the cell surface was regulated by the level of alpha-chain expression. It was also shown that cloned sublines of CEM cells which expressed different T cell antigen phenotypes differed in their response to TPA.