Role of the J-domain in the cooperation of Hsp40 with Hsp70

The Escherichia coli Hsp40 DnaJ and Hsp70 DnaK cooperate in the binding of proteins at intermediate stages of folding, assembly, and translocation across membranes. Binding of protein substrates to the DnaK C-terminal domain is controlled by ATP binding and hydrolysis in the N-terminal ATPase domain. The interaction of DnaJ with DnaK is mediated at least in part by the highly conserved N-terminal J-domain of DnaJ that includes residues 2–75. Heteronuclear NMR experiments with uniformly ¹⁵N-enriched DnaJ2–75 indicate that the chemical environment of residues located in helix II and the flanking loops is perturbed on interaction with DnaK or a truncated DnaK molecule, DnaK2–388. NMR signals corresponding to these residues broaden and exhibit changes in chemical shifts in the presence of DnaK(MgADP). Addition of MgATP largely reversed the broadening, indicating that NMR signals of DnaJ2–75 respond to ATP-dependent changes in DnaK. The J-domain interaction is localized to the ATPase domain of DnaK and is likely to be dominated by electrostatic interactions. The results suggest that the J-domain tethers DnaK to DnaJ-bound substrates, which DnaK then binds with its C-terminal peptide-binding domain.     

Preoperative Treatment Does Not Improve the Therapeutic Results of Abdominosacral Amputation of the Rectum

Background

This study reviewed the impact of preoperative chemoradiotherapy/short-term radiotherapy on abdominosacral amputations of the rectum (ASAR) for the treatment of low-rectum cancers in terms of postoperative morbidity, local recurrence rates, and survival.

Methods

A total of 198 patients with stage II and III tumors located within 6?cm of the anorectal junction underwent ASAR between 1998 and 2008 and were selected for further analysis. Patients were compared according to the following groups: those who had surgery only (Group A) and those who had preoperative chemoradiotherapy/short-term radiotherapy (Group B).

Results

There were 44 and 154 patients in Groups A and B, respectively, including 135 males. The median age of the subjects was 63?years (range?=?35–88). The median follow-up period was 81?months (range?=?23–138). Neither the local recurrence rates (6.8% in Group A vs. 4.6% in Group B, p?=?0.544) nor the 5-year relative survival rates (72.4% in Group A vs. 69.3% in Group B, p?=?0.127) differed significantly between the groups.

Conclusion

Preoperative therapy in low-rectum cancer does not improve the therapeutic results of ASAR.     

Skull Anatomy and Ontogeny of Legless Lizard Pseudopus apodus (Pallas, 1775): Heterochronic Influences on Form

Pseudopus apodus (Pallas, 1775) is the largest extant legless species of the subfamily Anguinae (Anguimorpha, Anguidae) living mostly in the sub‐arid territories ranging from the Balkan area in Europe to Kazakhstan in Asia. The species of other two genera live in North America, South‐East Asia and North Africa (Ophisaurus) and Europe and South‐West Asia (Anguis). The interrelationships of Anguinae are unresolved; this is in part the consequence of the insufficient knowledge of the cranial, postcranial and integumentary anatomy of the individual anguine species. The aim of this article is to fulfill this gap in our knowledge of the anguine anatomy. Now, in the first part of the project, the individual bones of the exocranium and visceral endocranium of the anguine legless lizard P. apodus are described in detail. In the present study, P. apodus is revealed to have autoapomorphic features of the skull which clearly distinguish it from Anguis and Ophisaurus. In addition, the study of posthatchling ontogeny of exocranium of P. apodus revealed some features, such as a nasal process of premaxilla being slightly widened in about its mid‐length, that are also typical for adults of the Ophisaurus and Anguis species as well as extinct species of Pseudopus. This strongly indicates that peramorphic heterochronic process played role in the evolution of the P. apodus skull. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:460–502, 2017. © 2016 Wiley Periodicals, Inc.     

Myoid (Muscular) Hamartoma of the Breast: Case Report and Review of the Literature

BACKGROUND: Myoid (muscular) hamartoma (MH) of the breast is a rare benign tumour-forming lesion composed of differentiated mammary glandular and stromal structures, fatty tissue, and areas of smooth muscle. It is considered to be a variant of mammary hamartoma. CASE REPORT: We report the case of a 46-year-old woman with MH, and provide a literature review explaining the origin of smooth muscle cells. Histologically, the tumour consisted of fibrolipomatous stroma containing ductal and lobular structures of the mammary gland located mainly at the tumour borders. The glandular structures showed signs of micro- and macrocystic changes, apocrine metaplasia, and adenosis. The dominant feature was the presence of a fascicular formation of spindle cells, predominantly in central parts, with incursion between glandular structures. Immunohistochemically, foci of smooth muscle tissue were positive for desmin, smooth muscle actin, and h-caldesmon. Oestrogen and progesterone receptors (PR) showed positive expression which was markedly higher for PR. There was negative expression of CD34, S-100 protein, and CD10. CONCLUSIONS: The origin of smooth muscle cells in MH is unknown. However, it is presumed to be derived from hormonally responsive breast stromal cells by smooth muscle metaplasia, based on evidence of hormone receptor expression in the lesion.     

Suite of finite element algorithms for accurate computation of soft tissue deformation for surgical simulation

Real time computation of soft tissue deformation is important for the use of augmented reality devices and for providing haptic feedback during operation or surgeon training. This requires algorithms that are fast, accurate and can handle material nonlinearities and large deformations. A set of such algorithms is presented in this paper, starting with the finite element formulation and the integration scheme used and addressing common problems such as hourglass control and locking. The computation examples presented prove that by using these algorithms, real time computations become possible without sacrificing the accuracy of the results. For a brain model having more than 7000 degrees of freedom, we computed the reaction forces due to indentation with frequency of around 1000 Hz using a standard dual core PC. Similarly, we conducted simulation of brain shift using a model with more than 50,000 degrees of freedom in less than one minute. The speed benefits of our models result from combining the Total Lagrangian formulation with explicit time integration and low order finite elements.     

One extraction tool for in vitro-in vivo extrapolation? SPME-based metabolomics of in vitro 2D, 3D,and in vivo mouse melanoma models

Solid phase microextraction (SPME) in combination with high-resolution mass spectrometry was employed for the determination of metabolomic profile of mouse melanoma growth within in vitro 2D, in vitro 3D, and in vivo models. Such multi-model approach had never been investigated before. Due to the low-invasiveness of SPME, it was possible to perform time-course analysis, which allowed building time profile of biochemical reactions in the studied material. Such approach does not require the multiplication of samples as subsequent analyses are performed from the very same cell culture or from the same individual. SPME already reduces the number of animals required for experiment; therefore, it is with good concordance with the 3Rs rule (replacement, reduction, and refinement). Among tested models, the largest number of compounds was found within the in vitro 2D cell culture model, while in vivo and in vitro 3D models had the lowest number of detected compounds. These results may be connected with a higher metabolic rate, as well as lower integrity of the in vitro 2D model compared to the in vitro 3D model resulting in a lower number of compounds released into medium in the latter model. In terms of in vitro-in vivo extrapolation, the in vitro 2D model performed more similar to in vivo model compared to in vitro 3D model; however, it might have been due to the fact that only compounds secreted to medium were investigated. Thus, in further experiments to obtain full metabolome information, the intraspheroidal assessment or spheroid dissociation would be necessary.