FE65 as a link between VLDLR and APP to regulate their trafficking and processing

<p>Abstract</p> <p>Background</p> <p>Several studies found that FE65, a cytoplasmic adaptor protein, interacts with APP and LRP1, altering the trafficking and processing of APP. We have previously shown that FE65 interacts with the ApoE receptor, ApoER2, altering its trafficking and processing. Interestingly, it has been shown that FE65 can act as a linker between APP and LRP1 or ApoER2. In the present study, we tested whether FE65 can interact with another ApoE receptor, VLDLR, thereby altering its trafficking and processing, and whether FE65 can serve as a linker between APP and VLDLR.</p> <p>Results</p> <p>We found that FE65 interacted with VLDLR using GST pull-down and co-immunoprecipitation assays in COS7 cells and in brain lysates. This interaction occurs via the PTB1 domain of FE65. Co-transfection with FE65 and full length VLDLR increased secreted VLDLR (sVLDLR); however, the levels of VLDLR C-terminal fragment (CTF) were undetectable as a result of proteasomal degradation. Additionally, FE65 increased cell surface levels of VLDLR. Moreover, we identified a novel complex between VLDLR and APP, which altered trafficking and processing of both proteins. Furthermore, immunoprecipitation results demonstrated that the presence of FE65 increased the interaction between APP and VLDLR <it>in vitro </it>and <it>in vivo</it>.</p> <p>Conclusions</p> <p>These data suggest that FE65 can regulate VLDLR trafficking and processing. Additionally, the interaction between VLDLR and APP altered both protein's trafficking and processing. Finally, our data suggest that FE65 serves as a link between VLDLR and APP. This novel interaction adds to a growing body of literature indicating trimeric complexes with various ApoE Receptors and APP.</p

Arthroscopic treatment of a medial meniscal cyst using a posterior trans-septal approach: a case report

Arthroscopic partial menisectomy followed by cyst decompression is currently recommended for treatment of a meniscal cyst. However, it is doubtful whether partial menisectomy should be performed on cysts communicating with the joint in cases without a meniscal tear on its surface since meniscal function will be sacrificed. In this report, a meniscal cyst arising from the posterior horn of the medial meniscus without meniscal tear on its surface was resected using an arthroscopic posterior trans-septal approach. A 59 year-old male presented to our hospital with popliteal pain when standing up after squatting down. Magnetic resonance imaging revealed a multilobulated meniscal cyst arising from the posterior horn of the medial meniscus extending to the posterior septum with a grade 2 meniscal tear by Mink's classification. The medial meniscus was intact on the surface on arthroscopic examination. The meniscal cyst and posterior septum were successfully resected using a posterior trans-septal approach without harming the meniscus. This is the first report on a meniscal cyst being resected using an arthroscopic posterior trans-septal approach with a 9-month follow-up period

Ultraviolet Laser Action in Ferromagnetic Zn1−xFexO Nanoneedles

Fe-doped ZnO nanoneedles (NDs) were fabricated by an Ar+ ion sputtering technique operated at room temperature. The as-grown samples show both ferromagnetic and lasing properties. The saturated magnetization moment was measured from 0.307 to 0.659 emu cm−3 at the field of 10 kOe with various Fe concentrations. Intense ultraviolet random lasing emission was observed from Zn1 − xFexO NDs at room temperature. The X-ray photoelectron spectroscopy result reveals that the doped Fe atoms occupy the Zn sites and lead to a decrease in oxygen deficiency

Hepatitis B and C virus prevalence in a rural area of South Korea: the role of acupuncture

A cross-sectional study evaluated the prevalence of and the risk factors for hepatitis C and B viruses among 700 adults above the age of 40 years in a rural area of South Korea. Seropositivity for hepatitis C virus antibody (11.0%, 95% confidence interval: 8.7–13.6) was higher than that for hepatitis B surface antigen (4.4%, 95% confidence interval: 3.0–6.2). Anti-hepatitis C virus seropositivity was associated with a history of repeated acupuncture (odds ratio=2.1, 95% confidence interval: 1.1–4.0), and blood transfusion (odds ratio=5.5, 95% confidence interval: 1.6–19.3) before 1992 when hepatitis C virus screening in blood donors became mandatory. Hepatitis C virus 2a was the most prevalent genotype, followed by 1b. Hepatitis C virus risk attributable to acupuncture was 38% (9% for men and 55% for women). Safer acupuncture practice has become a priority for hepatitis C virus prevention in South Korea

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie

Quantitative assay for the detection of the V617F variant in the Janus kinase 2 (JAK2) gene using the Luminex xMAP technology

<p>Abstract</p> <p>Background</p> <p>The availability of clinically valid biomarkers contribute to improve the diagnosis and clinical management of diseases. A valine-to-phenylalanine substitution at position 617 (V617F) in the Janus kinase 2 (JAK2) gene has been recently associated with key signaling abnormalities in the transduction of haemopoietic growth-factor receptors and is now considered as a useful clinical marker of myeloproliferative neoplasms. Several methods have recently been reported to detect the JAK2 V617F point mutation and show variable sensitivity.</p> <p>Methods</p> <p>Using the Luminex xMAP technology, we developed a quantitative assay to detect the JAK2V617F variant. The method was based on polymerase chain reaction (PCR) followed by hybridization to specific probes coupled with internally dyed microspheres. The assay comprises 3 steps: genomic DNA extraction, end point PCR reaction, direct hybridization of PCR fragments and quantification. It has been tested with different sources of nucleic acid.</p> <p>Results</p> <p>Applied to whole blood samples, this quantitative assay showed a limit of detection of 2%. A highly sensitive allele-specific primer extension reaction performed in parallel allowed to validate the results and to identify the specimens with values below 2%.</p> <p>Conclusion</p> <p>Direct hybridization assay using the Luminex xMAP technology allows sensitive quantification of JAK2V617F from blood spots. It is simple and can be easily performed in a clinical setting.</p

Estimation of Ligament Loading and Anterior Tibial Translation in Healthy and ACL-Deficient Knees During Gait and the Influence of Increasing Tibial Slope Using EMG-Driven Approach

The purpose of this study was to develop a biomechanical model to estimate anterior tibial translation (ATT), anterior shear forces, and ligament loading in the healthy and anterior cruciate ligament (ACL)-deficient knee joint during gait. This model used electromyography (EMG), joint position, and force plate data as inputs to calculate ligament loading during stance phase. First, an EMG-driven model was used to calculate forces for the major muscles crossing the knee joint. The calculated muscle forces were used as inputs to a knee model that incorporated a knee–ligament model in order to solve for ATT and ligament forces. The model took advantage of using EMGs as inputs, and could account for the abnormal muscle activation patterns of ACL-deficient gait. We validated our model by comparing the calculated results with previous in vitro, in vivo, and numerical studies of healthy and ACL-deficient knees, and this gave us confidence on the accuracy of our model calculations. Our model predicted that ATT increased throughout stance phase for the ACL-deficient knee compared with the healthy knee. The medial collateral ligament functioned as the main passive restraint to anterior shear force in the ACL-deficient knee. Although strong co-contraction of knee flexors was found to help restrain ATT in the ACL-deficient knee, it did not counteract the effect of ACL rupture. Posterior inclination angle of the tibial plateau was found to be a crucial parameter in determining knee mechanics, and increasing the tibial slope inclination in our model would increase the resulting ATT and ligament forces in both healthy and ACL-deficient knees

The management of the painful bipartite patella: a systematic review

Purpose: This study aimed to identify the most effective method for the treatment of the symptomatic bipartite patella. Methods: A systematic review of the literature was completed, and all studies assessing the management of a bipartite patella were included. Owing to the paucity of randomised controlled trials, a narrative review of 22 studies was completed. A range of treatments were assessed: conservative measures, open and arthroscopic fixation or excision and soft tissue release and excision. Results: All of the methods provided results ranging from good to excellent, with acceptable complication rates. Conclusions: This is a poorly answered treatment question. No firm guidance can be given as to the most appropriate method of treating the symptomatic bipartite patella. This study suggests that there are a number of effective treatments with acceptable complication rates and it may be that treatments that conserve the patella are more appropriate for larger fragments

Automatic segmentation of meningioma from non-contrasted brain MRI integrating fuzzy clustering and region growing

<p>Abstract</p> <p>Background</p> <p>In recent years, magnetic resonance imaging (MRI) has become important in brain tumor diagnosis. Using this modality, physicians can locate specific pathologies by analyzing differences in tissue character presented in different types of MR images.</p> <p>This paper uses an algorithm integrating fuzzy-c-mean (FCM) and region growing techniques for automated tumor image segmentation from patients with menigioma. Only non-contrasted T1 and T2 -weighted MR images are included in the analysis. The study's aims are to correctly locate tumors in the images, and to detect those situated in the midline position of the brain.</p> <p>Methods</p> <p>The study used non-contrasted T1- and T2-weighted MR images from 29 patients with menigioma. After FCM clustering, 32 groups of images from each patient group were put through the region-growing procedure for pixels aggregation. Later, using knowledge-based information, the system selected tumor-containing images from these groups and merged them into one tumor image. An alternative semi-supervised method was added at this stage for comparison with the automatic method. Finally, the tumor image was optimized by a morphology operator. Results from automatic segmentation were compared to the "ground truth" (GT) on a pixel level. Overall data were then evaluated using a quantified system.</p> <p>Results</p> <p>The quantified parameters, including the "percent match" (PM) and "correlation ratio" (CR), suggested a high match between GT and the present study's system, as well as a fair level of correspondence. The results were compatible with those from other related studies. The system successfully detected all of the tumors situated at the midline of brain.</p> <p>Six cases failed in the automatic group. One also failed in the semi-supervised alternative. The remaining five cases presented noticeable edema inside the brain. In the 23 successful cases, the PM and CR values in the two groups were highly related.</p> <p>Conclusions</p> <p>Results indicated that, even when using only two sets of non-contrasted MR images, the system is a reliable and efficient method of brain-tumor detection. With further development the system demonstrates high potential for practical clinical use.</p

Toward a Detailed Description of the Thermally Induced Dynamics of the Core Promoter

Establishing the general and promoter-specific mechanistic features of gene transcription initiation requires improved understanding of the sequence-dependent structural/dynamic features of promoter DNA. Experimental data suggest that a spontaneous dsDNA strand separation at the transcriptional start site is likely to be a requirement for transcription initiation in several promoters. Here, we use Langevin molecular dynamic simulations based on the Peyrard-Bishop-Dauxois nonlinear model of DNA (PBD LMD) to analyze the strand separation (bubble) dynamics of 80-bp-long promoter DNA sequences. We derive three dynamic criteria, bubble probability, bubble lifetime, and average strand separation, to characterize bubble formation at the transcriptional start sites of eight mammalian gene promoters. We observe that the most stable dsDNA openings do not necessarily coincide with the most probable openings and the highest average strand displacement, underscoring the advantages of proper molecular dynamic simulations. The dynamic profiles of the tested mammalian promoters differ significantly in overall profile and bubble probability, but the transcriptional start site is often distinguished by large (longer than 10 bp) and long-lived transient openings in the double helix. In support of these results are our experimental transcription data demonstrating that an artificial bubble-containing DNA template is transcribed bidirectionally by human RNA polymerase alone in the absence of any other transcription factors