Human Cytomegalovirus glycoprotein UL16 causes intracellular sequestration of NKG2D ligands, protecting against NK cell cytotoxicity.

The activating receptor, NKG2D, is expressed on a variety of immune effector cells and recognizes divergent families of major histocompatibility complex (MHC) class I-related ligands, including the MIC and ULBP proteins. Infection, stress, or transformation can induce NKG2D ligand expression, resulting in effector cell activation and killing of the ligand-expressing target cell. The human cytomegalovirus (HCMV) membrane glycoprotein, UL16, binds to three of the five known ligands for human NKG2D. UL16 is retained in the endoplasmic reticulum and cis-Golgi apparatus of cells and causes MICB to be similarly retained and stabilized within cells. Coexpression of UL16 markedly reduces cell surface levels of MICB, ULBP1, and ULBP2, and decreases susceptibility to natural killer cell-mediated cytotoxicity. Domain swapping experiments demonstrate that the transmembrane and cytoplasmic domains of UL16 are important for intracellular retention of UL16, whereas the ectodomain of UL16 participates in down-regulation of NKG2D ligands. The intracellular sequestration of NKG2D ligands by UL16 represents a novel HCMV immune evasion mechanism to add to the well-documented viral strategies directed against antigen presentation by classical MHC molecules

Improving the Longevity and Results of Mastopexy and Breast Reduction Procedures: Reconstructing an Internal Breast Support System with Biocompatible Mesh to Replace the Supporting Function of the Ligamentous Suspension

The original publication is available at http://www.springerlink.com/Publication of this article was funded by the Stellenbosch University Open Access Fund.The reasons for recurrent ptosis in mastopexy and breast reduction procedures are twofold. First, available surgical techniques do not reconstruct the normal breast anatomy responsible for maintaining breast shape. Second, in many instances the techniques rely on atrophied tissue to provide long-term support. The discovery in 1997 of the ligamentous suspension (the supporting system of the breast) gave rise to the concept that reconstruction of this anatomical structure was needed to ensure a sustained postoperative result. Applying the latest knowledge regarding the structural and vascular anatomy of the breast in the surgical technique and utilizing material other than atrophied breast tissue enabled us to prevent the recurrence of breast ptosis. Methods A surgical technique was developed to replace the supportive function of a failed ligamentous suspension in 112 patients with ptotic breasts. This was done by reconstructing an internal breast-supporting system (IBSS) with biocompatible mesh. Results Satisfactory breast shape, nipple projection, and upper breast fullness was obtained with this technique in mastopexy patients with moderate-sized ptotic breasts. In patients with larger breasts good results were obtained with a simultaneous breast reduction. The longest follow-up is 6 years 3 months. Conclusions With this technique recurrent breast ptosis can be prevented in mastopexy and breast reduction procedures. The results are such that it eliminates the need for silicone prostheses to obtain satisfactory upper-breast fullness. The surgical technique is especially indicated in patients with skin of poor quality or patients with high expectations.Stellenbosch University Open Access FundPublishers' Versio

Femoral artery thrombosis after internal fixation of a transverse acetabular fracture in a patient with osteogenesis imperfecta type I

Osteogenesis imperfecta is a genetic disorder characterized by increased susceptibility to fractures and vascular injuries due to connective tissue fragility. In this case report, we present a patient with osteogenesis imperfecta type I who sustained a transverse fracture of the right acetabulum while transferring from bed to chair. The fracture was repaired through an ilioinguinal approach. During the surgery, an iatrogenic injury to the femoral artery and vein occurred. This intraoperative complication was salvaged by immediate vascular repair. We discuss the possible causes of iatrogenic vascular injuries in patients with osteogenesis imperfecta. Orthopaedic surgeons should be aware of this potentially devastating complication in this particular patient cohort

Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats

The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

Deep generative modeling for single-cell transcriptomics.

Single-cell transcriptome measurements can reveal unexplored biological diversity, but they suffer from technical noise and bias that must be modeled to account for the resulting uncertainty in downstream analyses. Here we introduce single-cell variational inference (scVI), a ready-to-use scalable framework for the probabilistic representation and analysis of gene expression in single cells ( https://github.com/YosefLab/scVI ). scVI uses stochastic optimization and deep neural networks to aggregate information across similar cells and genes and to approximate the distributions that underlie observed expression values, while accounting for batch effects and limited sensitivity. We used scVI for a range of fundamental analysis tasks including batch correction, visualization, clustering, and differential expression, and achieved high accuracy for each task

A new interpretation of total column BrO during Arctic spring

Emission of bromine from sea-salt aerosol, frost flowers, ice leads, and snow results in the nearly complete removal of surface ozone during Arctic spring. Regions of enhanced total column BrO observed by satellites have traditionally been associated with these emissions. However, airborne measurements of BrO and O3 within the convective boundary layer (CBL) during the ARCTAS and ARCPAC field campaigns at times bear little relation to enhanced column BrO. We show that the locations of numerous satellite BrO "hotspots" during Arctic spring are consistent with observations of total column ozone and tropopause height, suggesting a stratospheric origin to these regions of elevated BrO. Tropospheric enhancements of BrO large enough to affect the column abundance are also observed, with important contributions originating from above the CBL. Closure of the budget for total column BrO, albeit with significant uncertainty, is achieved by summing observed tropospheric partial columns with calculated stratospheric partial columns provided that natural, short-lived biogenic bromocarbons supply between 5 and 10 ppt of bromine to the Arctic lowermost stratosphere. Proper understanding of bromine and its effects on atmospheric composition requires accurate treatment of geographic variations in column BrO originating from both the stratosphere and troposphere. Copyright 2010 by the American Geophysical Union

Anomalies and the chiral magnetic effect in the Sakai-Sugimoto model

In the chiral magnetic effect an imbalance in the number of left- and right-handed quarks gives rise to an electromagnetic current parallel to the magnetic field produced in noncentral heavy-ion collisions. The chiral imbalance may be induced by topologically nontrivial gluon configurations via the QCD axial anomaly, while the resulting electromagnetic current itself is a consequence of the QED anomaly. In the Sakai-Sugimoto model, which in a certain limit is dual to large-N_c QCD, we discuss the proper implementation of the QED axial anomaly, the (ambiguous) definition of chiral currents, and the calculation of the chiral magnetic effect. We show that this model correctly contains the so-called consistent anomaly, but requires the introduction of a (holographic) finite counterterm to yield the correct covariant anomaly. Introducing net chirality through an axial chemical potential, we find a nonvanishing vector current only before including this counterterm. This seems to imply the absence of the chiral magnetic effect in this model. On the other hand, for a conventional quark chemical potential and large magnetic field, which is of interest in the physics of compact stars, we obtain a nontrivial result for the axial current that is in agreement with previous calculations and known exact results for QCD.Comment: 35 pages, 4 figures, v2: added comments about frequency-dependent conductivity at the end of section 4; references added; version to appear in JHE

ChIPseqR: analysis of ChIP-seq experiments

<p>Abstract</p> <p>Background</p> <p>The use of high-throughput sequencing in combination with chromatin immunoprecipitation (ChIP-seq) has enabled the study of genome-wide protein binding at high resolution. While the amount of data generated from such experiments is steadily increasing, the methods available for their analysis remain limited. Although several algorithms for the analysis of ChIP-seq data have been published they focus almost exclusively on transcription factor studies and are usually not well suited for the analysis of other types of experiments.</p> <p>Results</p> <p>Here we present ChIPseqR, an algorithm for the analysis of nucleosome positioning and histone modification ChIP-seq experiments. The performance of this novel method is studied on short read sequencing data of <it>Arabidopsis thaliana </it>mononucleosomes as well as on simulated data.</p> <p>Conclusions</p> <p>ChIPseqR is shown to improve sensitivity and spatial resolution over existing methods while maintaining high specificity. Further analysis of predicted nucleosomes reveals characteristic patterns in nucleosome sequences and placement.</p

Automated and unsupervised detection of malarial parasites in microscopic images

<p>Abstract</p> <p>Background</p> <p>Malaria is a serious infectious disease. According to the World Health Organization, it is responsible for nearly one million deaths each year. There are various techniques to diagnose malaria of which manual microscopy is considered to be the gold standard. However due to the number of steps required in manual assessment, this diagnostic method is time consuming (leading to late diagnosis) and prone to human error (leading to erroneous diagnosis), even in experienced hands. The focus of this study is to develop a robust, unsupervised and sensitive malaria screening technique with low material cost and one that has an advantage over other techniques in that it minimizes human reliance and is, therefore, more consistent in applying diagnostic criteria.</p> <p>Method</p> <p>A method based on digital image processing of Giemsa-stained thin smear image is developed to facilitate the diagnostic process. The diagnosis procedure is divided into two parts; enumeration and identification. The image-based method presented here is designed to automate the process of enumeration and identification; with the main advantage being its ability to carry out the diagnosis in an unsupervised manner and yet have high sensitivity and thus reducing cases of false negatives.</p> <p>Results</p> <p>The image based method is tested over more than 500 images from two independent laboratories. The aim is to distinguish between positive and negative cases of malaria using thin smear blood slide images. Due to the unsupervised nature of method it requires minimal human intervention thus speeding up the whole process of diagnosis. Overall sensitivity to capture cases of malaria is 100% and specificity ranges from 50-88% for all species of malaria parasites.</p> <p>Conclusion</p> <p>Image based screening method will speed up the whole process of diagnosis and is more advantageous over laboratory procedures that are prone to errors and where pathological expertise is minimal. Further this method provides a consistent and robust way of generating the parasite clearance curves.</p