Die UVB-abhängige Induktion des Vaskulären Endothelialen Wachstumsfaktors (VEGF) wird in epidermalen Zellen autokrin durch den Transformierenden Wachstumsfaktor alpha (TGF@) reguliert: Bedeutung für die UVB-induzierte

Ein Zusammenhang zwischen chronischer Sonnenexposition der Haut und vermehrter Bildung von Gefäßen bei der Photoalterung und Photokarzinogenese der Haut mit vorzeitiger Alterung und Ausbildung nicht-melanozytärer und melanozytärer Tumoren der Haut kann als wissenschaftlich gesichert angesehen werden. Teleangiektasien, die durch eine Zunahme und Vergrößerung kutaner Blutgefäße gekennzeichnet sind, und die Entwicklung stark vaskularisierter Hauttumoren sind charakteristische Endpunkte einer chronisch sonnenexponierten und sonnengeschädigten Haut. Die zugrundeliegenden molekularen Mechanismen der UV-induzierten pathophysiologischen Angiogenese sind weitgehend unbekannt. In der Tumorprogression sind Angiogenesefaktoren wie der vaskuläre endotheliale Wachstumsfaktor VEGF, ein multifunktionales Zytokin mit mitogener Aktivität für Endothelzellen, von zentraler Bedeutung, da Tumorwachstum und -metastasierung von der Ausbildung eines tumorversorgenden Blutgefäßsystems abhängig sind. In der vorliegenden Arbeit sollte mit molekularbiologischen und zellbiologischen Methoden untersucht werden, ob und in welcher Form solare UVB-Strahlung als schädigende Komponente des Sonnenlichts auf der Erdoberfläche die Regulation von VEGF beeinflußt. Es konnte gezeigt werden, daß UVB-Bestrahlung den Angiogenesefaktor VEGF in epidermalen Zellen auf Proteinebene mit biphasischer Expression nach 4 bzw. 24 h maximal induziert. In Untersuchungen der UVB-induzierten VEGF-Promotoraktivität wurde durch transiente Transfektionen von HaCaT-Zellen mit Deletionskonstrukten des humanen VEGF-Promotors und in Experimenten unter Verwendung neutralisierender Antikörper der transformierende Wachstumsfaktor alpha (TGF) als Mediator der sekundären VEGF-Expression nach UVBBestrahlung identifiziert. Die primäre Induktion von VEGF und die Synthese von TGF sind abhängig von der UVB-Aktivierung des EGF-Rezeptors (EGF-R) und konnten durch den EGF-R-spezifischen Tyrosinkinase-Inhibitor PD 153035 signifikant inhibiert werden. Die UVB-abhängige VEGF-Expression wurde in vivo in menschlicher Haut immunohistologisch bestätigt. Durch die signifikante Verminderung der UVB-abhängig gesteigerten Angiogenese in der Epidermis repetitiv bestrahlter haarloser Mäuse konnte nach intraperitonealer Injektion neutralisierender Antikörper gegen VEGF die kausale Bedeutung von VEGF in vivo im Mausmodell belegt werden. Zusammengefaßt konnten in dieser Arbeit in vitro und in vivo die Bedeutung von VEGF für angiogenetische Prozesse nach UVB-Exposition herausgearbeitet und wesentliche Wege seiner Signaltransduktion identifiziert werden

Subunits of the Histone Chaperone CAF1 Also Mediate Assembly of Protamine-Based Chromatin

One of the most dramatic forms of chromatin reorganization occurs during spermatogenesis, when the paternal genome is repackaged from a nucleosomal to a protamine-based structure. We assessed the role of the canonical histone chaperone CAF1 in Drosophila spermatogenesis. In this process, CAF1 does not behave as a complex, but its subunits display distinct chromatin dynamics. During histone-to-protamine replacement, CAF1-p180 dissociates from the DNA while CAF1-p75 binds and stays on as a component of sperm chromatin. Association of CAF1-p75 with the paternal genome depends on CAF1-p180 and protamines. Conversely, CAF1-p75 binds protamines and is required for their incorporation into sperm chromatin. Histone removal, however, occurs independently of CAF1 or protamines. Thus, CAF1-p180 and CAF1-p75 function in a temporal hierarchy during sperm chromatin assembly, with CAF1-p75 acting as a protamine-loading factor. These results show that CAF1 subunits mediate the assembly of two fundamentally different forms of chromatin

Evaluation of range of motion restriction within the hip joint

In Total Hip Arthroplasty, determining the impingement free range of motion requirement is a complex task. This is because in the native hip, motion is restricted by both impingement as well as soft tissue restraint. The aim of this study is to determine a range of motion benchmark which can identify motions which are at risk from impingement and those which are constrained due to soft tissue. Two experimental methodologies were used to determine motions which were limited by impingement and those motions which were limited by both impingement and soft tissue restraint. By comparing these two experimental results, motions which were limited by impingement were able to be separated from those motions which were limited by soft tissue restraint. The results show motions in extension as well as flexion combined with adduction are limited by soft tissue restraint. Motions in flexion, flexion combined with abduction and adduction are at risk from osseous impingement. Consequently, these motions represent where the maximum likely damage will occur in femoroacetabular impingement or at most risk of prosthetic impingement in Total Hip Arthroplasty

Comparison of Functional and Clinical Outcomes between Minimally-Invasive and Conventional Approaches after Total Hip Replacement

Background: Total Hip Arthroplasty (THA) is one of the most commonly performed and successful orthopaedic surgeries. At the same time, the issue about the best surgical approach for THA remains controversial. This systematic review aims to evaluate the current evidence for the use of Minimally-Invasive Surgery (MIS) in THA. Methods: A systematic literature search of PubMed, Medline and Embase was conducted. Randomised controlled trials, comparative studies, and cohort studies were included in this systematic review. Main outcome measurements included incision length, blood loss, operating time, length of stay, complications, postoperative pain on a Visual Analogue Scale (VAS), Short Form 36/12 Health Survey (SF 36/12), Harris Hip Score (HHS) and cup inclination. Results: A total of 30 studies met the inclusion criteria. There was no significant difference between MIS and conventional approaches for THA with regards to complication rates and implant inclination angle. The average operating time in 10/24 (41%) studies was significantly (p<0.05) longer in the MIS group. MIS THA lead to an improvement, patient-centered results with reduced blood loss in 9/16 (56%), reduced use of analgesics in 4/4 (100%) and reduced myoglobin correlated muscle trauma in 3/4 (75%) of the analysed studies. Additionally, 10/10 (100%) studies reported less postoperative pain after MIS THA, 16/19 (84%) studies detected an improved postoperative Harris Hip score and 7/7 (100%) studies an improved SF36/12 score respectively. This resulted a reduced length of stay in 10/10 (100%) of the studies when compared to THA utilizing a conventional approach. Conclusion: MIS in THA is nowadays no longer seen as just cosmetically attractive but rather as a real improvement for the clinical outcome. There is evidence for improved patient related outcome following MIS THA

CTCF induces histone variant incorporation, erases the H3K27me3 histone mark and opens chromatin

Insulators functionally separate active chromatin domains frominactive ones. The insulator factor, CTCF, has been found to bind to boundaries and to mediate insulator function. CTCF binding sites are depleted for the histone modification H3K27me3 and are enriched for the histone variant H3.3. In order to determine whether demethylation of H3K27me3 and H3.3 incorporation are a requirement for CTCF binding at domain boundaries or whether CTCF causes these changes, we made use of the LacI DNA binding domain to control CTCF binding by the Lac inducer IPTG. Here we show that, in contrast to the related factor CTCFL, the N-terminus plus zinc finger domain of CTCF is sufficient to open compact chromatin rapidly. This is preceded by incorporation of the histone variant H3.3, which thereby removes the H3K27me3 mark. This demonstrates the causal role for CTCF in generating the chromatin features found at insulators. Thereby, spreading of a histone modification from one domain through the insulator into the neighbouring domain is inhibited

Use of antagonist muscle EMG in the assessment of neuromuscular health of the low back

Background: Non-specific low back pain (LBP) has been one of the most frequently occurring musculoskeletal problems. Impairment in the mechanical stability of the lumbar spine has been known to lower the safety margin of the spine musculature and can result in the occurrence of pain symptoms of the low back area. Previously, changes in spinal stability have been identified by investigating recruitment patterns of low back and abdominal muscles in laboratory experiments with controlled postures and physical activities that were hard to conduct in daily life. The main objective of this study was to explore the possibility of developing a reliable spine stability assessment method using surface electromyography (EMG) of the low back and abdominal muscles in common physical activities. Methods: Twenty asymptomatic young participants conducted normal walking, plank, and isometric back extension activities prior to and immediately after maintaining a 10-min static upper body deep flexion on a flat bed. EMG data of the erector spinae, external oblique, and rectus abdominals were collected bilaterally, and their mean normalized amplitude values were compared between before and after the static deep flexion. Changes in the amplitude and co-contraction ratio values were evaluated to understand how muscle recruitment patterns have changed after the static deep flexion. Results: Mean normalized amplitude of antagonist muscles (erector spinae muscles while conducting plank; external oblique and rectus abdominal muscles while conducting isometric back extension) decreased significantly (P &lt; 0.05) after the 10-min static deep flexion. Normalized amplitude of agonist muscles did not vary significantly after deep flexion. Conclusions: Results of this study suggest the possibility of using surface EMG in the evaluation of spinal stability and low back health status in simple exercise postures that can be done in non-laboratory settings. Specifically, amplitude of antagonist muscles was found to be more sensitive than agonist muscles in identifying changes in the spinal stability associated with the 10-min static deep flexion. Further research with various loading conditions and physical activities need to be performed to improve the reliability and utility of the findings of the current study.open0

Choice of binding sites for CTCFL compared to CTCF is driven by chromatin and by sequence preference

The two paralogous zinc finger factors CTCF and CTCFL differ in expression such that CTCF is ubiquitously expressed, whereas CTCFL is found during spermatogenesis and in some cancer types in addition to other cell types. Both factors share the highly conserved DNA binding domain and are bound to DNA sequences with an identical consensus. In contrast, both factors differ substantially in the number of bound sites in the genome. Here, we addressed the molecular features for this binding specificity. In contrast to CTCF we found CTCFL highly enriched at 'open' chromatin marked by H3K27 acetylation, H3K4 di- and trimethylation, H3K79 dimethylation and H3K9 acetylation plus the histone variant H2A.Z. CTCFL is enriched at transcriptional start sites and regions bound by transcription factors. Consequently, genes deregulated by CTCFL are highly cell specific. In addition to a chromatin-driven choice of binding sites, we determined nucleotide positions critical for DNA binding by CTCFL, but not by CTCF