Genes Encoding Structural Proteins of Epidermal Cornification and S100 Calcium-Binding Proteins Form a Gene Complex (“Epidermal Differentiation Complex”) on Human Chromosome 1q21

Chromosome 1 reveals in region 1q21 a most remarkable density of genes that fulfill important functions in terminal differentiation of the human epidermis. These genes encode the cornified envelope precursors loricrin, involucrin, and small proline-rich proteins (SPRR1, SPRR2, and SPRR3), the intermediate filament-associated proteins profilaggrin and trichohyalin, and several S100A calcium-binding proteins. Extending and refining our previous physical map of 1q21 we have now mapped two additional S100A genes as well as the three SPRR subfamilles and resolved the arrangement of involucrin, SPRRs, and loricrin. All genes are linked within 1.9 Mbp of human genomic DNA in the order: S100A10, trichohyalin, profilaggrin, involucrin, SPRR3, SPRR1B, SPRR2A, loricrin, S100A9, S100A8, S100A6. Co-localization of genes expressed late during maturation of epidermal cells together with genes encoding calcium-binding proteins is particularly intriguing since calcium levels tightly control the differentiation of epithelial cells and the expression of genes encoding epidermal structural proteins. Accounting for the close functional cooperation among these structurally and evolutionary related genes, we conclude that these loci constitute a gene complex, for which we propose the name epidermal differentiation complex

An immunohistochemical study of the tissue bridging adult spondylolytic defects—the presence and significance of fibrocartilaginous entheses

Introduction Spondylolytic spondylolisthesis is an osseous discontinuity of the vertebral arch that predominantly affects the fifth lumbar vertebra. Biomechanical factors are closely related to the condition. An immunohistochemical investigation of lysis-zone tissue obtained from patients with isthmic spondylolisthesis was performed to determine the molecular composition of the lysis-zone tissue and enable interpretation of the mechanical demands to which the tissue is subject. Methods: During surgery, the tissue filling the spondylytic defects was removed from 13 patients. Twelve spondylolistheses were at the L5/S1 level with slippage being less than Meyerding grade II. Samples were methanol fixed, decalcified and cryosectioned. Sections were labelled with a panel of monoclonal antibodies directed against collagens, glycosaminoglycans and proteoglycans. Results: The lysis-zone tissue had an ordered collagenous structure with distinct fibrocartilaginous entheses at both ends. Typically, these had zones of calcified and uncalcified fibrocartilage labelling strongly for type II collagen and aggrecan. Labelling was also detected around bony spurs that extended from the enthesis into the lysis-zone. The entheses also labelled for types I, III and VI collagens, chondroitin four and six sulfate, keratan and dermatan sulfate, link protein, versican and tenascin. Conclusions: Although the gap filled by the lysis tissue is a pathological feature, the tissue itself has hallmarks of a normal ligament—i.e. fibrocartilaginous entheses at either end of an ordered collagenous fibre structure. The fibrocartilage is believed to dissipate stress concentration at the hard/soft tissue boundary. The widespread occurrence of molecules typical of cartilage in the attachment of the lysis tissue, suggests that compressive and shear forces are present to which the enthesis is adapted, in addition to the expected tensile forces across the spondylolysis. Such a combination of tensile, shear and compressive forces must operate whenever there is any opening or closing of the spondylolytic ga

The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization

Circadian clocks are molecular timekeeping mechanisms that allow organisms to anticipate daily changes in their environment. The fundamental cellular basis of these clocks is delayed negative feedback gene regulation with PERIOD and CRYPTOCHROME containing protein complexes as main inhibitory elements. For a correct circadian period, it is essential that such clock protein complexes accumulate in the nucleus in a precisely timed manner, a mechanism that is poorly understood. We performed a systematic RNAi-mediated screen in human cells and identified 15 genes associated with the nucleo-cytoplasmic translocation machinery, whose expression is important for circadian clock dynamics. Among them was Transportin 1 (TNPO1), a non-classical nuclear import carrier, whose knockdown and knockout led to short circadian periods. TNPO1 was found in endogenous clock protein complexes and particularly binds to PER1 regulating its (but not PER2's) nuclear localization. While PER1 is also transported to the nucleus by the classical, Importin beta-mediated pathway, TNPO1 depletion slowed down PER1 nuclear import rate as revealed by fluorescence recovery after photobleaching (FRAP) experiments. In addition, we found that TNPO1-mediated nuclear import may constitute a novel input pathway of how cellular redox state signals to the clock, since redox stress increases binding of TNPO1 to PER1 and decreases its nuclear localization. Together, our RNAi screen knocking down import carriers (but also export carriers) results in short and long circadian periods indicating that the regulatory pathways that control the timing of clock protein subcellular localization are far more complex than previously assumed. TNPO1 is one of the novel players essential for normal circadian periods and potentially for redox regulation of the clock

Histological analysis of surgical lumbar intervertebral disc tissue provides evidence for an association between disc degeneration and increased body mass index

<p>Abstract</p> <p>Background</p> <p>Although histopathological grading systems for disc degeneration are frequently used in research, they are not yet integrated into daily care routine pathology of surgical samples. Therefore, data on histopathological changes in surgically excised disc material and their correlation to clinical parameters such as age, gender or body mass index (BMI) is limited to date. The current study was designed to correlate major physico-clinical parameters from a population of orthopaedic spine center patients (gender, age and BMI) with a quantitative histologic degeneration score (HDS).</p> <p>Methods</p> <p>Excised lumbar disc material from 854 patients (529 men/325 women/mean age 56 (15-96) yrs.) was graded based on a previously validated histologic degeneration score (HDS) in a cohort of surgical disc samples that had been obtained for the treatment of either disc herniation or discogenic back pain. Cases with obvious inflammation, tumor formation or congenital disc pathology were excluded. The degree of histological changes was correlated with sex, age and BMI.</p> <p>Results</p> <p>The HDS (0-15 points) showed significantly higher values in the nucleus pulposus (NP) than in the annulus fibrosus (AF) (Mean: NP 11.45/AF 7.87), with a significantly higher frequency of histomorphological alterations in men in comparison to women. Furthermore, the HDS revealed a positive significant correlation between the BMI and the extent of histological changes. No statistical age relation of the degenerative lesions was seen.</p> <p>Conclusions</p> <p>This study demonstrated that histological disc alterations in surgical specimens can be graded in a reliable manner based on a quantitative histologic degeneration score (HDS). Increased BMI was identified as a positive risk factor for the development of symptomatic, clinically significant disc degeneration.</p

Untersuchung der Eignung von formändernden begreifbaren Schnittstellen zur Kommunikation von Unsicherheit

Uncertainty is intrinsic to human nature, and in many real world scenarios it is unavoidable. On a daily basis, humans interact with a multitude of different devices, and the importance of uncertainty in data increases steadily. To name just a few, uncertainty can be found in machine learning or weather forecasts, but also in user inputs like calorie intake. While previous work has shown that people prefer the communication of uncertainty on output, it is still unclear if the same holds true for user input. Furthermore, the means of uncertain input communication is a field that has scarcely been explored yet. Nevertheless, to produce valid outputs containing uncertainty, the input uncertainty has to be quantified first. In this thesis we propose nine shape-changing tangible interfaces that support uncertain input. Based on the results of a preliminary study in form of a focus group, we have determined the most promising design and present an implementation of a shape-changing slider. In order to evaluate this design, we conducted an explorative user study. Results of the study show that users prefer to have the possibility of uncertain input. In addition, the prototype was rated to be very suitable for uncertain input with an average rating of 6.83 on a 7 point Likert scale. On a higher level, this provides evidence that shape-changing tangible interfaces fit the task of communicating uncertainty. Overall, the predominantly positive user feedback shows promise in uncertain input communication and encourages future exploration.Unsicherheit liegt in der Natur des Menschen und ist in vielen realen Szenarien unvermeidbar. Täglich interagieren Menschen mit einer Vielfalt von Geräten und Daten-Unsicherheit spielt dabei eine immer wichtigere Rolle. Diese Unsicherheit kann unter anderem im Maschinenlernen oder in Wettervorhersagen gefunden werden, aber auch in Nutzereingaben wie der Kalorienzufuhr. Obwohl bisherige Forschung für Ausgaben gezeigt hat, dass Menschen die Kommunikation von Unsicherheit bevorzugen, ist noch unklar, ob selbiges auch für Eingaben zutrifft. Ferner sind die Möglichkeiten für solche Eingaben mit Unsicherheit kaum erforscht. Um jedoch valide Ausgaben mit Unsicherheit produzieren zu können, muss zunächst die Eingabe-Unsicherheit quantifiziert werden. In dieser Arbeit schlagen wir neun formändernde, greifbare Nutzerschnittstellen vor, die Eingaben mit Unsicherheit unterstützen. Basierend auf den Ergebnissen einer Vorstudie haben wir das vielversprechendste Design ermittelt und präsentieren die Implementierung eines formändernden Sliders. Wir führten eine explorative Nutzerstudie durch, um dieses Design zu evaluieren. Die Ergebnisse zeigen, dass Nutzer die Möglichkeit für Eingaben mit Unsicherheit bevorzugen. Zudem wurde der Prototyp als geignet für Eingaben mit Unsicherheit befunden mit einerW ertung von 6,83 auf einer 7-punktigen Likert-Skala. Auf einer höheren Abstraktionsebene weist dies nach, dass formändernde, greifbare Schnittstellen für diese Aufgabe geeignet sind. Im Allgemeinen zeigt die vorwiegend positive Nutzerresonanz, dass die Kommunikation von Eingabe-Unsicherheit vielversprechend ist, und motiviert weitere Erforschung

Extending Input Space of Tangible Dials and Sliders for Uncertain Input

International audienceUncertainty is common when working with data and becomes more important as processing big data gains attention. However, no standard tangible interface element exists for inputting uncertain data. In this article, we extend the input space of two traditional TUIs: dial and slider. We present five designs that are based on dials and sliders and support uncertain input. We conduct focus group interviews to evaluate the designs. The interviews allow us to extend existing design requirements for parameter control UIs to support uncertain input

Clinical and Radiological Outcome of a new Total Cervical Disc Replacement Design

Study Design: Non-randomized prospective and single center clinical trial of the ProDisc Vivo prosthesis. Objective: Investigate the clinical and radiological results of a refined cTDR - the ProDisc Vivo - with two years of follow up (FU). The incidence of implant-related complications was recorded as a secondary outcome variable. Summary of Background Data: Previous generations of the ProDisc artificial cervical disc replacement generate high primary stability due to keel-based designs with opening of the anterior cortex during the implantation and subsequent high rates of heterotopic ossifications. Methods: Clinical outcome scores included the Neck Disability Index (NDI), Visual Analogue Scale (VAS), arm and neck pain self-assessment questionnaires. The radiological outcome included the range of motion (ROM) and the occurrence of heterotopic ossifications. The incidence of implant-related complications with new implant design was recorded as a secondary outcome variable. Results: A total of 55 patients received a single level treatment with the ProDisc Vivo cTDR between C3/4 and C6/7, with a follow up rate of 78%. The clinical outcome scores improved in all parameters significantly (p = 0.0001) (NDI: 68.3 → 17.4; VAS arm: 6.3 → 1.4; VAS neck: 4.9 → 1.6). The ROM of the index-segment didn't show a significant change (p = 0.26) (7.9° → 9.2°). Heterotopic ossifications at the index segment was found as grade 0 in 58%, grade 1 in 22%, grade 2 in 10%, grade 3 (with functional impairment of the prosthesis) in 7% and grade 4 in 3% of the cases. We observed three implant-related complications (5.5%), with two implant dislocations anteriorly and one low-grade infect. Conclusion: cTDR with ProDisc Vivo demonstrated a significant and sustained improvement of all clinical outcome parameters. A less-invasive implantation mechanism with lower primary stability of the cTDR might be a reason for a higher dislocation rate compared to the keel-based previous generation ProDisc C.ISSN:0362-2436ISSN:1528-115

An immunohistochemical study of the tissue bridging adult spondylolytic defects—the presence and significance of fibrocartilaginous entheses

Introduction Spondylolytic spondylolisthesis is an osseous discontinuity of the vertebral arch that predominantly affects the fifth lumbar vertebra. Biomechanical factors are closely related to the condition. An immunohistochemical investigation of lysis-zone tissue obtained from patients with isthmic spondylolisthesis was performed to determine the molecular composition of the lysis-zone tissue and enable interpretation of the mechanical demands to which the tissue is subject. Methods: During surgery, the tissue filling the spondylytic defects was removed from 13 patients. Twelve spondylolistheses were at the L5/S1 level with slippage being less than Meyerding grade II. Samples were methanol fixed, decalcified and cryosectioned. Sections were labelled with a panel of monoclonal antibodies directed against collagens, glycosaminoglycans and proteoglycans. Results: The lysis-zone tissue had an ordered collagenous structure with distinct fibrocartilaginous entheses at both ends. Typically, these had zones of calcified and uncalcified fibrocartilage labelling strongly for type II collagen and aggrecan. Labelling was also detected around bony spurs that extended from the enthesis into the lysis-zone. The entheses also labelled for types I, III and VI collagens, chondroitin four and six sulfate, keratan and dermatan sulfate, link protein, versican and tenascin. Conclusions: Although the gap filled by the lysis tissue is a pathological feature, the tissue itself has hallmarks of a normal ligament—i.e. fibrocartilaginous entheses at either end of an ordered collagenous fibre structure. The fibrocartilage is believed to dissipate stress concentration at the hard/soft tissue boundary. The widespread occurrence of molecules typical of cartilage in the attachment of the lysis tissue, suggests that compressive and shear forces are present to which the enthesis is adapted, in addition to the expected tensile forces across the spondylolysis. Such a combination of tensile, shear and compressive forces must operate whenever there is any opening or closing of the spondylolytic gap