94 research outputs found

    National survey in Switzerland calls for improved diagnosis and treatment in children with scabies

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    AIM OF THE STUDY: The global prevalence of scabies is estimated to be up to 200 million cases annually, with young children particularly affected. In Europe, most cases are thought to originate in migrant populations. Scabies management is challenging in children. To identify knowledge gaps and research needs, we aimed to descriptively evaluate the management of children with scabies by different Swiss healthcare providers. METHODS: An invitation for an anonymous online survey (36 questions) was sent to members of Swiss societies of dermatologists, general practitioners, paediatricians, paediatric dermatologists, paediatric infectious diseases specialists, and tropical medicine specialists, inviting clinicians to participate from 25th May to 8th August 2020. One reminder invitation was sent. Hospital pharmacies and the distributor of permethrin were contacted to report consumption trends of scabicides in 2018 and 2019. RESULTS: The survey was completed by 248 clinicians: 146 (59%) paediatricians, 47 (19%) dermatologists, 28 (11%) general practitioners, 6 (2%) paediatric dermatologists, 13 (5%) paediatric infectious diseases specialists, and 8 (3%) tropical medicine specialists. Most consulted up to 10 scabies cases within a 16-month period, with similar numbers in migrant and Swiss children. Dermoscopy was used by 24% of non-dermatologists. Non-dermatologists did not consider co-treatment of close contacts in up to 59% of cases. While permethrin was the first-line treatment, treatment failures were frequently reported in children aged <5 years. Up to 67% of paediatric dermatologists regularly used oral ivermectin off-label in children weighing <15 kg. None of the paediatric dermatologists, 15% of the dermatologists, and 9% of the non-dermatologists used only one treatment cycle.Scabicide consumption increased. Treatment studies on ivermectin use in children weighing <15 kg had the highest research priority. CONCLUSION: In Switzerland, scabies is a frequent dermatosis in migrant and Swiss children. While accessible, optimal diagnostics are underutilised, and treatment is suboptimal. Permethrin resistance appears to be an increasing problem. Dermatologists regularly use ivermectin off-label in children weighing <15 kg. Treatment studies on ivermectin use in children weighing <15 kg, user-friendly diagnostic tools, new treatment protocols, and child-friendly dosage forms are needed to improve the diagnosis and treatment of children with scabies

    Mouse cytoplasmic dynein intermediate chains: identification of new isoforms, alternative splicing and tissue distribution of transcripts

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    BACKGROUND: Intracellular transport of cargoes including organelles, vesicles, signalling molecules, protein complexes, and RNAs, is essential for normal function of eukaryotic cells. The cytoplasmic dynein complex is an important motor that moves cargos along microtubule tracks within the cell. In mammals this multiprotein complex includes dynein intermediate chains 1 and 2 which are encoded by two genes, Dync1i1 and Dync1i2. These proteins are involved in dynein cargo binding and dynein complexes with different intermediate chains bind to specific cargoes, although the mechanisms to achieve this are not known. The DYNC1I1 and DYNC1I2 proteins are translated from different splice isoforms, and specific forms of each protein are essential for the function of different dynein complexes in neurons. METHODOLOGY/PRINCIPAL FINDINGS: Here we have undertaken a systematic survey of the dynein intermediate chain splice isoforms in mouse, basing our study on mRNA expression patterns in a range of tissues, and on bioinformatics analysis of mouse, rat and human genomic and cDNA sequences. We found a complex pattern of alternative splicing of both dynein intermediate chain genes, with maximum complexity in the embryonic and adult nervous system. We have found novel transcripts, including some with orthologues in human and rat, and a new promoter and alternative non-coding exon 1 for Dync1i2. CONCLUSIONS/SIGNIFICANCE: These data, including the cloned isoforms will be essential for understanding the role of intermediate chains in the cytoplasmic dynein complex, particularly their role in cargo binding within individual tissues including different brain regions

    CG2Real: Improving the Realism of Computer Generated Images using a Large Collection of Photographs

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    Computer Graphics (CG) has achieved a high level of realism, producing strikingly vivid images. This realism, however, comes at the cost of long and often expensive manual modeling, and most often humans can still distinguish between CG images and real images. We present a novel method to make CG images look more realistic that is simple and accessible to novice users. Our system uses a large collection of photographs gathered from online repositories. Given a CG image, we retrieve a small number of real images with similar global structure. We identify corresponding regions between the CG and real images using a novel mean-shift cosegmentation algorithm. The user can then automatically transfer color, tone, and texture from matching regions to the CG image. Our system only uses image processing operations and does not require a 3D model of the scene, making it fast and easy to integrate into digital content creation workflows. Results of a user study show that our improved CG images appear more realistic than the originals

    A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes

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    Cytoplasmic dynein is the multisubunit motor protein for retrograde movement of diverse cargoes to microtubule minus ends. Here, we investigate the function of dynein variants, defined by different intermediate chain (IC) isoforms, by expressing fluorescent ICs in neuronal cells. Green fluorescent protein (GFP)–IC incorporates into functional dynein complexes that copurify with membranous organelles. In living PC12 cell neurites, GFP–dynein puncta travel in both the anterograde and retrograde directions. In cultured hippocampal neurons, neurotrophin receptor tyrosine kinase B (TrkB) signaling endosomes are transported by cytoplasmic dynein containing the neuron-specific IC-1B isoform and not by dynein containing the ubiquitous IC-2C isoform. Similarly, organelles containing TrkB isolated from brain by immunoaffinity purification also contain dynein with IC-1 but not IC-2 isoforms. These data demonstrate that the IC isoforms define dynein populations that are selectively recruited to transport distinct cargoes

    Consensus nomenclature for dyneins and associated assembly factors.

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    Dyneins are highly complex, multicomponent, microtubule-based molecular motors. These enzymes are responsible for numerous motile behaviors in cytoplasm, mediate retrograde intraflagellar transport (IFT), and power ciliary and flagellar motility. Variants in multiple genes encoding dyneins, outer dynein arm (ODA) docking complex subunits, and cytoplasmic factors involved in axonemal dynein preassembly (DNAAFs) are associated with human ciliopathies and are of clinical interest. Therefore, clear communication within this field is particularly important. Standardizing gene nomenclature, and basing it on orthology where possible, facilitates discussion and genetic comparison across species. Here, we discuss how the human gene nomenclature for dyneins, ODA docking complex subunits, and DNAAFs has been updated to be more functionally informative and consistent with that of the unicellular green alga Chlamydomonas reinhardtii, a key model organism for studying dyneins and ciliary function. We also detail additional nomenclature updates for vertebrate-specific genes that encode dynein chains and other proteins involved in dynein complex assembly

    Phosphorylation regulates targeting of cytoplasmic dynein to kinetochores during mitosis

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    Cytoplasmic dynein functions at several sites during mitosis; however, the basis of targeting to each site remains unclear. Tandem mass spectrometry analysis of mitotic dynein revealed a phosphorylation site in the dynein intermediate chains (ICs) that mediates binding to kinetochores. IC phosphorylation directs binding to zw10 rather than dynactin, and this interaction is needed for kinetochore dynein localization. Phosphodynein associates with kinetochores from nuclear envelope breakdown to metaphase, but bioriented microtubule (MT) attachment and chromosome alignment induce IC dephosphorylation. IC dephosphorylation stimulates binding to dynactin and poleward streaming. MT depolymerization, release of kinetochore tension, and a PP1-Ξ³ mutant each inhibited IC dephosphorylation, leading to the retention of phosphodynein at kinetochores and reduced poleward streaming. The depletion of kinetochore dynactin by moderate levels of p50(dynamitin) expression disrupted the ability of dynein to remove checkpoint proteins by streaming at metaphase but not other aspects of kinetochore dynein activity. Together, these results suggest a new model for localization of kinetochore dynein and the contribution of kinetochore dynactin

    Cytoplasmic dynein nomenclature

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    A variety of names has been used in the literature for the subunits of cytoplasmic dynein complexes. Thus, there is a strong need for a more definitive consensus statement on nomenclature. This is especially important for mammalian cytoplasmic dyneins, many subunits of which are encoded by multiple genes. We propose names for the mammalian cytoplasmic dynein subunit genes and proteins that reflect the phylogenetic relationships of the genes and the published studies clarifying the functions of the polypeptides. This nomenclature recognizes the two distinct cytoplasmic dynein complexes and has the flexibility to accommodate the discovery of new subunits and isoforms

    Video face replacement

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    We present a method for replacing facial performances in video. Our approach accounts for differences in identity, visual appearance, speech, and timing between source and target videos. Unlike prior work, it does not require substantial manual operation or complex acquisition hardware, only single-camera video. We use a 3D multilinear model to track the facial performance in both videos. Using the corresponding 3D geometry, we warp the source to the target face and retime the source to match the target performance. We then compute an optimal seam through the video volume that maintains temporal consistency in the final composite. We showcase the use of our method on a variety of examples and present the result of a user study that suggests our results are difficult to distinguish from real video footage.National Science Foundation (U.S.) (Grant PHY-0835713)National Science Foundation (U.S.) (Grant DMS-0739255
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