Loss of ADAM9 expression impairs beta 1 integrin endocytosis, focal adhesion formation and cancer cell migration

The transmembrane protease ADAM9 is frequently upregulated in human cancers, and it promotes tumour progression in mice. In vitro, ADAM9 regulates cancer cell adhesion and migration by interacting with integrins. However, how ADAM9 modulates integrin functions is not known. We here show that ADAM9 knockdown increases beta 1 integrin levels through mechanisms that are independent of its protease activity, in ADAM9-silenced cells, adhesion to collagen and fibronectin is reduced, suggesting an altered function of the accumulated integrins. Mechanistically, ADAM9 co-immunoprecipitates with beta 1 integrin, and both internalization and subsequent degradation of beta 1 integrin are significantly decreased in ADAM9-silenced cells, with no effect on beta 1 integrin recycling. Accordingly, the formation of focal adhesions and actin stress fibres in ADAM9-silenced cells is altered, possibly explaining the reduction in cell adhesion and migration in these cells. Taken together, our data provide mechanistic insight into the ADAM9-integrin interaction, demonstrating that ADAM9 regulates beta 1 integrin endocytosis. Moreover, our findings indicate that the reduced migration of ADAM9-silenced cells is, at least in part, caused by the accumulation and altered activity of beta 1 integrin at the cell surface

Low frequency radio properties of the z>5 quasar population

Optically luminous quasars at z > 5 are important probes of super-massive black hole (SMBH) formation. With new and future radio facilities, the discovery of the brightest low-frequency radio sources in this epoch would be an important new probe of cosmic reionization through 21-cm absorption experiments. In this work, we systematically study the low-frequency radio properties of a sample of 115 known spectroscopically confirmed z > 5 quasars using the second data release of the Low Frequency Array (LOFAR) Two Metre Sky survey (LoTSS-DR2), reaching noise levels of ∼80 µJy beam−1 (at 144 MHz) over an area of ∼ 5720 deg2 . We find that 41 sources (36%) are detected in LoTSS-DR2 at > 2σ significance and we explore the evolution of their radio properties (power, spectral index, and radio loudness) as a function of redshift and rest-frame ultra-violet properties. We obtain a median spectral index of −0.29+0.10 −0.09 by stacking 93 quasars using LoTSS-DR2 and Faint Images of the Radio Sky at Twenty Centimetres (FIRST) data at 1.4 GHz, in line with observations of quasars at z < 3. We compare the radio loudness of the high-z quasar sample to a lower-z quasar sample at z ∼ 2 and find that the two radio loudness distributions are consistent with no evolution, although the low number of high-z quasars means that we cannot rule out weak evolution. Furthermore, we make a first order empirical estimate of the z = 6 quasar radio luminosity function, which is used to derive the expected number of high-z sources that will be detected in the completed LoTSS survey. This work highlights the fact that new deep radio observations can be a valuable tool in selecting high-z quasar candidates for follow-up spectroscopic observations by decreasing contamination of stellar dwarfs and reducing possible selection biases introduced by strict colour cuts

Answer changing in multiple choice assessment change that answer when in doubt – and spread the word!

<p>Abstract</p> <p>Background</p> <p>Several studies during the last decades have shown that answer changing in multiple choice examinations is generally beneficial for examinees. In spite of this the common misbelief still prevails that answer changing in multiple choice examinations results in an increased number of wrong answers rather than an improved score. One suggested consequence of newer studies is that examinees should be informed about this misbelief in the hope that this prejudice might be eradicated. This study aims to confirm data from previous studies about the benefits of answer changing as well as pursue the question of whether students informed about the said advantageous effects of answer changing would indeed follow this advice and change significantly more answers. Furthermore a look is cast on how the overall examination performance and mean point increase of these students is affected.</p> <p>Methods</p> <p>The answer sheets to the end of term exams of 79 3^rdyear medical students at the University of Munich were analysed to confirm the benefits of answer changing. Students taking the test were randomized into two groups. Prior to taking the test 41 students were informed about the benefits of changing answers after careful reconsideration while 38 students did not receive such information. Both groups were instructed to mark all answer changes made during the test.</p> <p>Results</p> <p>Answer changes were predominantly from wrong to right in full accordance with existing literature resources. It was shown that students who had been informed about the benefits of answer changing when in doubt changed answers significantly more often than students who had not been informed. Though students instructed on the benefits of changing answers scored higher in their exams than those not instructed, the difference in point increase was not significant.</p> <p>Conclusion</p> <p>Students should be informed about the benefits of changing initial answers to multiple choice questions once when in reasonable doubt about these answers. Furthermore, reconsidering answers should be encouraged as students will heed the advice and change more answers than students not so instructed.</p

Effective Batalin--Vilkovisky theories, equivariant configuration spaces and cyclic chains

Kontsevich's formality theorem states that the differential graded Lie algebra of multidifferential operators on a manifold M is L-infinity-quasi-isomorphic to its cohomology. The construction of the L-infinity map is given in terms of integrals of differential forms on configuration spaces of points in the upper half-plane. Here we consider configuration spaces of points in the disk and work equivariantly with respect to the rotation group. This leads to considering the differential graded Lie algebra of multivector fields endowed with a divergence operator. In the case of R^d with standard volume form, we obtain an L-infinity morphism of modules over this differential graded Lie algebra from cyclic chains of the algebra of functions to multivector fields. As a first application we give a construction of traces on algebras of functions with star-products associated with unimodular Poisson structures. The construction is based on the Batalin--Vilkovisky quantization of the Poisson sigma model on the disk and in particular on the treatment of its zero modes.Comment: 27 page

Comparative study of single and multislice computed tomography for assessment of the mandibular canal

OBJECTIVE: The purpose of this study was to evaluate the accuracy of relative measurements from the roof of the mandibular canal to the alveolar crest in multislice (multidetector) computed tomography (MDCT) and single-slice computed tomography (SSCT). MATERIAL AND METHODS: The sample consisted of 26 printed CT films (7 SSCT and 19 MDCT) from the files of the LABI-3D (3D Imaging Laboratory) of the School of Dentistry of the University of São Paulo (FOUSP), which had been acquired using different protocols. Two observers analyzed in a randomized and independent order a series of 22 oblique CT reconstructions of each patient. Each observer analyzed the CT scans twice. The length of the mandibular canal and the distance between the mandibular canal roof and the crest of the alveolar ridge were obtained. Dahlberg test was used for statistical analysis. RESULTS: The mean error found for the mandibular canal length measurements obtained from SSCT was 0.53 mm in the interobserver analysis, and 0.38 mm for both observers. On MDCT images, the mean error was 0.0 mm in the interobserver analysis, and 0.0 and 0.23 mm in the intraobserver analysis. Regarding the distance between the mandibular canal roof and the alveolar bone crest, the SSCT images showed a mean error of 1.16 mm in the interobserver analysis and 0.66 and 0.59 mm in the intraobserver analysis. In the MDCT images, the mean error was 0.72 mm in the interobserver analysis and 0.50 and 0.54 mm in the intraobserver analysis. CONCLUSION: Multislice CT was demonstrated a more accurate method and demonstrated high reproducibility in the analysis of important anatomical landmarks for planning of mandibular dental implants, namely the mandibular canal pathway and alveolar crest height

Biocybernetic Adaptation Strategies: Machine awareness of human state for improved operational performance

Human operators interacting with machines or computers continually adapt to the needs of the system ideally resulting in optimal performance. In some cases, however, deteriorated performance is an outcome. Adaptation to the situation is a strength expected of the human operator which is often accomplished by the human through self-regulation of mental state. Adaptation is at the core of the human operator’s activity, and research has demonstrated that the implementation of a feedback loop can enhance this natural skill to improve training and human/machine interaction. Biocybernetic adaptation involves a “loop upon a loop,” which may be visualized as a superimposed loop which senses a physiological signal and influences the operator’s task at some point. Biocybernetic adaptation in, for example, physiologically adaptive automation employs the “steering” sense of “cybernetic,” and serves a transitory adaptive purpose – to better serve the human operator by more fully representing their responses to the system. The adaptation process usually makes use of an assessment of transient cognitive state to steer a functional aspect of a system that is external to the operator’s physiology from which the state assessment is derived. Therefore, the objective of this paper is to detail the structure of biocybernetic systems regarding the level of engagement of interest for adaptive systems, their processing pipeline, and the adaptation strategies employed for training purposes, in an effort to pave the way towards machine awareness of human state for self-regulation and improved operational performance

A profile of hospital-admitted paediatric burns patients in South Africa

<p>Abstract</p> <p>Background</p> <p>Injuries and deaths from burns are a serious, yet preventable health problem globally. This paper describes burns in a cohort of children admitted to the Red Cross Children's Hospital, in Cape Town, South Africa.</p> <p>This six month retrospective case note review looked at a sample of consecutively admitted patients from the 1 ^stApril 2007 to the 30 ^thSeptember 2007. Information was collected using a project-specific data capture sheet. Descriptive statistics (percentages, medians, means and standard deviations) were calculated, and data was compared between age groups. Spearman's correlation co-efficient was employed to look at the association between the total body surface area and the length of stay in hospital.</p> <p>Findings</p> <p>During the study period, 294 children were admitted (f= 115 (39.1%), m= 179 (60.9%)). Hot liquids caused 83.0% of the burns and 36.0% of these occurred in children aged two years or younger. Children over the age of five were equally susceptible to hot liquid burns, but the mechanism differed from that which caused burns in the younger child.</p> <p>Conclusion</p> <p>In South Africa, most hospitalised burnt children came from informal settlements where home safety is a low priority. Black babies and toddlers are most at risk for sustaining severe burns when their environment is disorganized with respect to safety. Burns injuries can be prevented by improving the home environment and socio-economic living conditions through the health, social welfare, education and housing departments.</p

Epidermal growth factor suppresses induction by progestin of the adhesion protein desmoplakin in T47D breast cancer cells

INTRODUCTION: Although the effects of progesterone on cell cycle progression are well known, its role in spreading and adhesion of breast cancer cells has not attracted much attention until recently. Indeed, by controlling cell adhesion proteins, progesterone may play a direct role in breast cancer invasion and metastasis. Progesterone has also been shown to modulate epidermal growth factor (EGF) effects in neoplasia, although EGF effects on progesterone pathways and targets are less well understood. In the present study we identify an effect of EGF on a progesterone target, namely desmoplakin. METHODS: Initially flow cytometry was used to establish the growing conditions and demonstrate that the T47D breast cancer cell line was responding to progesterone and EGF in a classical manner. Differential display RT-PCR was employed to identify differentially expressed genes affected by progesterone and EGF. Western and Northern blotting were used to verify interactions between EGF and progesterone in three breast cancer cell lines: T47D, MCF-7, and ZR-75. RESULTS: We found the cell adhesion protein desmoplakin to be upregulated by progesterone – a process that was suppressed by EGF. This appears to be a general but not universal effect in breast cancer cell lines. CONCLUSION: Our findings suggest that progesterone and EGF may play opposing roles in metastasis. They also suggest that desmoplakin may be a useful biomarker for mechanistic studies designed to analyze the crosstalk between EGF and progesterone dependent events. Our work may help to bridge the fields of metastasis and differentiation, and the mechanisms of steroid action