Lipodystrophy as a late effect after stem cell transplantation

Survivors of childhood cancer are at high risk of developing metabolic diseases in adulthood. Recently, several patients developing partial lipodystrophy following hematopoietic stem cell transplantation (HSCT) have been described. In this review, we summarize the cases described so far and discuss potential underlying mechanisms of the disease. The findings suggest that HSCT-associated lipodystrophies may be seen as a novel form of acquired lipodystrophy

Ultrasound Liver Fibrosis Diagnosis using Multi-indicator guided Deep Neural Networks

Accurate analysis of the fibrosis stage plays very important roles in follow-up of patients with chronic hepatitis B infection. In this paper, a deep learning framework is presented for automatically liver fibrosis prediction. On contrary of previous works, our approach can take use of the information provided by multiple ultrasound images. An indicator-guided learning mechanism is further proposed to ease the training of the proposed model. This follows the workflow of clinical diagnosis and make the prediction procedure interpretable. To support the training, a dataset is well-collected which contains the ultrasound videos/images, indicators and labels of 229 patients. As demonstrated in the experimental results, our proposed model shows its effectiveness by achieving the state-of-the-art performance, specifically, the accuracy is 65.6%(20% higher than previous best).Comment: Jiali Liu and Wenxuan Wang are equal contributio

Trace species detection in the near infrared using Fourier transform broadband cavity enhanced absorption spectroscopy: Initial studies on potential breath analytes

Cavity enhanced absorption measurements have been made of several species that absorb light between 1.5 and 1.7 µm using both a supercontinuum source and superluminescent light emitting diodes. A system based upon an optical enhancement cavity of relatively high finesse, consisting of mirrors of reflectivity ∼99.98%, and a Fourier transform spectrometer, is demonstrated. Spectra are recorded of isoprene, butadiene, acetone and methane, highlighting problems with spectral interference and unambiguous concentration determinations. Initial results are presented of acetone within a breath-like matrix indicating ppm precision at <∼10 ppm acetone levels. Instrument sensitivities are sufficiently enhanced to enable the detection of atmospheric levels of methane. Higher detection sensitivities are achieved using the supercontinuum source, with a minimum detectable absorption coefficient of ∼4 × 10(-9) cm(-1) reported within a 4 min acquisition time. Finally, two superluminescent light emitting diodes are coupled together to increase the wavelength coverage, and measurements are made simultaneously on acetylene, CO(2), and butadiene. The absorption cross-sections for acetone and isoprene have been measured with an instrumental resolution of 4 cm(-1) and are found to be 1.3 ± 0.1 × 10(-21) cm(2) at a wavelength of 1671.9 nm and 3.6 ± 0.2 × 10(-21) cm(2) at 1624.7 nm, respectively

A recurrent germline mutation in the 5’UTR of the androgen receptor causes complete androgen insensitivity by activating aberrant uORF translation

A subset of patients with monogenic disorders lacks disease causing mutations in the protein coding region of the corresponding gene. Here we describe a recurrent germline mutation found in two unrelated patients with complete androgen insensitivity syndrome (CAIS) generating an upstream open reading frame (uORF) in the 5' untranslated region (5'-UTR) of the androgen receptor (AR) gene. We show in patient derived primary genital skin fibroblasts as well as in cell-based reporter assays that this mutation severely impacts AR function by reducing AR protein levels without affecting AR mRNA levels. Importantly, the newly generated uORF translates into a polypeptide and the expression level of this polypeptide inversely correlates with protein translation from the primary ORF of the AR thereby providing a model for AR-5'UTR mediated translational repression. Our findings not only add a hitherto unrecognized genetic cause to complete androgen insensitivity but also underline the importance of 5'UTR mutations affecting uORFs for the pathogenesis of monogenic disorders in general

Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model

Exosomes are endosome-derived small membrane vesicles that are secreted by most cell types including tumor cells. Tumor-derived exosomes usually contain tumor antigens and have been used as a source of tumor antigens to stimulate anti-tumor immune responses. However, many reports also suggest that tumor-derived exosomes can facilitate tumor immune evasion through different mechanisms, most of which are antigen-independent. In the present study we used a mouse model of delayed-type hypersensitivity (DTH) and demonstrated that local administration of tumor-derived exosomes carrying the model antigen chicken ovalbumin (OVA) resulted in the suppression of DTH response in an antigen-specific manner. Analysis of exosome trafficking demonstrated that following local injection, tumor-derived exosomes were internalized by CD11c+ cells and transported to the draining LN. Exosome-mediated DTH suppression is associated with increased mRNA levels of TGF-β1 and IL-4 in the draining LN. The tumor-derived exosomes examined were also found to inhibit DC maturation. Taken together, our results suggest a role for tumor-derived exosomes in inducing tumor antigen-specific immunosuppression, possibly by modulating the function of APCs. © 2011 Yang et al

Recent Updates in Meat Color Research: Integrating Traditional and High-Throughput Approaches

Deviation from a bright cherry-red color of fresh meat results in less consumer acceptance and either discounted or discarded products in the value chain. Tissue homeostasis changes immediately after exsanguination, leading to acidification of muscle. Any alteration in pH drop can influence both muscle structure and enzymatic activity related to oxygen consumption and the redox state of myoglobin. This review focuses on both fundamental and applied approaches to under-stand the effects of pH on biochemical changes, oxygen diffusion, and its impact on meat color. Recent updates utilizing high-throughput “omics” approaches to elucidate the biochemical changes associated with high-pH meat are also dis-cussed. The fundamental aspects affecting fresh meat color are complex and highly interrelated with factors ranging from live animal production to preharvest environmental issues, muscle to meat conversion, and numerous facets along the merchandising chain of marketing meat to consumers

Scrapie-Specific Pathology of Sheep Lymphoid Tissues

Transmissible spongiform encephalopathies (TSEs) or prion diseases often result in accumulation of disease-associated PrP (PrPd) in the lymphoreticular system (LRS), specifically in association with follicular dendritic cells (FDCs) and tingible body macrophages (TBMs) of secondary follicles. We studied the effects of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and electron microscopy. FDCs of sheep were grouped according to morphology as immature, mature or regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrPd was located using immunogold labelling at the plasmalemma of FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph nodes, macrophages outside the follicle and a proportion of germinal centre TBMs accumulated PrPd within endosomes and lysosomes. In addition, TBMs showed PrPd in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin. These observations suggest that PrPd is internalised via the caveolin-mediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs and TBMs differs from those of scrapie infected neurones and glial cells suggesting that different PrPd/cell membrane interactions occur in different cell types

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes

Vesicle miR-195 derived from endothelial cells inhibits expression of serotonin transporter in vessel smooth muscle cells

Serotonin or 5-hydroxytryptamine (5-HT) has been shown to be essential in lots of physiological and pathological processes. It is well known that 5-HT and 5-HT transporter (5-HTT) play important roles in the pulmonary artery in pulmonary hypertension. However, little is known about the function of 5-HTT in other arteries. In this study we found that the expression of 5-HTT was elevated in injured carotid arteries and over-expression of 5-HTT induced proliferation of smooth muscle cells (SMCs); however, this phenotype could be reversed by knocking-down of 5-HTT or endothelial cells conditional medium (EC-CM). A 5-HTT inhibitor, fluoxetine, treated animals also exhibited reduced restenosis after injury. We identified that miR-195 was packaged in the extracellular vesicles from EC-CM. We further confirmed that extracellular vesicles could transfer miR-195 from ECs to SMCs to inhibit the expression of 5-HTT in SMCs and the proliferation of SMCs. These results provide the first evidence that ECs communicate with SMCs via micro-RNA195 in the regulation of the proliferation of SMCs through 5-HTT, which will contribute to a better understanding of communications between ECs and SMCs via micro-RNA. Our findings suggest a potential target for the control of vessel restenosis