UNC93B1 recruits syntenin-1 to dampen TLR7 signalling and prevent autoimmunity.

At least two members of the Toll-like receptor (TLR) family, TLR7 and TLR9, can recognize self-RNA and self-DNA, respectively. Despite the structural and functional similarities between these receptors, their contributions to autoimmune diseases such as systemic lupus erythematosus can differ. For example, TLR7 and TLR9 have opposing effects in mouse models of systemic lupus erythematosus-disease is exacerbated in TLR9-deficient mice but attenuated in TLR7-deficient mice1. However, the mechanisms of negative regulation that differentiate between TLR7 and TLR9 are unknown. Here we report a function for the TLR trafficking chaperone UNC93B1 that specifically limits signalling of TLR7, but not TLR9, and prevents TLR7-dependent autoimmunity in mice. Mutations in UNC93B1 that lead to enhanced TLR7 signalling also disrupt binding of UNC93B1 to syntenin-1, which has been implicated in the biogenesis of exosomes2. Both UNC93B1 and TLR7 can be detected in exosomes, suggesting that recruitment of syntenin-1 by UNC93B1 facilitates the sorting of TLR7 into intralumenal vesicles of multivesicular bodies, which terminates signalling. Binding of syntenin-1 requires phosphorylation of UNC93B1 and provides a mechanism for dynamic regulation of TLR7 activation and signalling. Thus, UNC93B1 not only enables the proper trafficking of nucleic acid-sensing TLRs, but also sets the activation threshold of potentially self-reactive TLR7

ShuffleDet: Real-Time Vehicle Detection Network in On-board Embedded UAV Imagery

On-board real-time vehicle detection is of great significance for UAVs and other embedded mobile platforms. We propose a computationally inexpensive detection network for vehicle detection in UAV imagery which we call ShuffleDet. In order to enhance the speed-wise performance, we construct our method primarily using channel shuffling and grouped convolutions. We apply inception modules and deformable modules to consider the size and geometric shape of the vehicles. ShuffleDet is evaluated on CARPK and PUCPR+ datasets and compared against the state-of-the-art real-time object detection networks. ShuffleDet achieves 3.8 GFLOPs while it provides competitive performance on test sets of both datasets. We show that our algorithm achieves real-time performance by running at the speed of 14 frames per second on NVIDIA Jetson TX2 showing high potential for this method for real-time processing in UAVs.Comment: Accepted in ECCV 2018, UAVision 201

Effects of qigong training on physical and psychosocial well-being of breast cancer survivors: a systematic review

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Bandit-based Random Mutation Hill-Climbing

The Random Mutation Hill-Climbing algorithm is a direct search technique mostly used in discrete domains. It repeats the process of randomly selecting a neighbour of a best-so-far solution and accepts the neighbour if it is better than or equal to it. In this work, we propose to use a novel method to select the neighbour solution using a set of independent multi-armed bandit-style selection units which results in a bandit-based Random Mutation Hill-Climbing algorithm. The new algorithm significantly outperforms Random Mutation Hill-Climbing in both OneMax (in noise-free and noisy cases) and Royal Road problems (in the noise-free case). The algorithm shows particular promise for discrete optimisation problems where each fitness evaluation is expensive

De novo assembly and characterization of Camelina sativa transcriptome by paired-end sequencing

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Mediation of short and longer term effects of an intervention program to enhance resilience in immigrants from Mainland China to Hong Kong

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Bifidobacterial Dominance of the Gut in Early Life and Acquisition of Antimicrobial Resistance.

Bifidobacterium species are important commensals capable of dominating the infant gut microbiome, in part by producing acids that suppress growth of other taxa. Bifidobacterium species are less prone to possessing antimicrobial resistance (AMR) genes (ARGs) than other taxa that may colonize infants. Given that AMR is a growing public health crisis and ARGs are present in the gut microbiome of humans from early life, this study examines the correlation between a Bifidobacterium-dominated infant gut microbiome and AMR levels, measured by a culture-independent metagenomic approach both in early life and as infants become toddlers. In general, Bifidobacterium dominance is associated with a significant reduction in AMR in a Bangladeshi cohort, both in the number of acquired AMR genes present and in the abundance of AMR genes. However, by year 2, Bangladeshi infants had no significant differences in AMR related to their early-life Bifidobacterium levels. A generalized linear model including all infants in a previously published Swedish cohort found a significant negative association between log-transformed total AMR and Bifidobacterium levels, thus confirming the relationship between Bifidobacterium levels and AMR. In both cohorts, there was no change between early-life and later-life AMR abundance in high-Bifidobacterium infants but a significant reduction in AMR abundance in low-Bifidobacterium infants. These results support the hypothesis that early Bifidobacterium dominance of the infant gut microbiome may help reduce colonization by taxa containing ARGs.IMPORTANCE Infants are vulnerable to an array of infectious diseases, and as the gut microbiome may serve as a reservoir of AMR for pathogens, reducing the levels of AMR in infants is important to infant health. This study demonstrates that high levels of Bifidobacterium are associated with reduced levels of AMR in early life and suggests that probiotic interventions to increase infant Bifidobacterium levels have the potential to reduce AMR in infants. However, this effect is not sustained at year 2 of age in Bangladeshi infants, underscoring the need for more detailed studies of the biogeography and timing of infant AMR acquisition

Rapid influx and death of plasmacytoid dendritic cells in lymph nodes mediate depletion in acute simian immunodeficiency virus infection

Plasmacytoid dendritic cells (pDC) are essential innate immune system cells that are lost from the circulation in human immunodeficiency virus (HIV)-infected individuals associated with CD4+ T cell decline and disease progression. pDC depletion is thought to be caused by migration to tissues or cell death, although few studies have addressed this directly. We used precise methods of enumeration and in vivo labeling with 5-bromo-2′-deoxyuridine to track recently divided pDC in blood and tissue compartments of monkeys with acute pathogenic simian immunodeficiency virus (SIV) infection. We show that pDC are lost from blood and peripheral lymph nodes within 14 days of infection, despite a normal frequency of pDC in bone marrow. Paradoxically, pDC loss masked a highly dynamic response characterized by rapid pDC mobilization into blood and a 10- to 20-fold increase in recruitment to lymph nodes relative to uninfected animals. Within lymph nodes, pDC had increased levels of apoptosis and necrosis, were uniformly activated, and were infected at frequencies similar to CD4+ T cells. Nevertheless, remaining pDC had essentially normal functional responses to stimulation through Toll-like receptor 7, with half of lymph node pDC producing both TNF-α and IFN-α. These findings reveal that cell migration and death both contribute to pDC depletion in acute SIV infection. We propose that the rapid recruitment of pDC to inflamed lymph nodes in lentivirus infection has a pathologic consequence, bringing cells into close contact with virus, virus-infected cells, and pro-apoptotic factors leading to pDC death. © 2009 Brown et al

Evolving Game Skill-Depth using General Video Game AI agents

Most games have, or can be generalised to have, a number of parameters that may be varied in order to provide instances of games that lead to very different player experiences. The space of possible parameter settings can be seen as a search space, and we can therefore use a Random Mutation Hill Climbing algorithm or other search methods to find the parameter settings that induce the best games. One of the hardest parts of this approach is defining a suitable fitness function. In this paper we explore the possibility of using one of a growing set of General Video Game AI agents to perform automatic play-testing. This enables a very general approach to game evaluation based on estimating the skill-depth of a game. Agent-based play-testing is computationally expensive, so we compare two simple but efficient optimisation algorithms: the Random Mutation Hill-Climber and the Multi-Armed Bandit Random Mutation Hill-Climber. For the test game we use a space-battle game in order to provide a suitable balance between simulation speed and potential skill-depth. Results show that both algorithms are able to rapidly evolve game versions with significant skill-depth, but that choosing a suitable resampling number is essential in order to combat the effects of noise

Global small RNA analysis in fast-growing Arabidopsis thaliana with elevated concentrations of ATP and sugars

BACKGROUND: In higher eukaryotes, small RNAs play a role in regulating gene expression. Overexpression (OE) lines of Arabidopsis thaliana purple acid phosphatase 2 (AtPAP2) were shown to grow faster and exhibit higher ATP and sugar contents. Leaf microarray studies showed that many genes involved in microRNAs (miRNAs) and trans-acting siRNAs (tasiRNAs) biogenesis were significantly changed in the fast-growing lines. In this study, the sRNA profiles of the leaf and the root of 20-day-old plants were sequenced and the impacts of high energy status on sRNA expression were analyzed. RESULTS: 9-13 million reads from each library were mapped to genome. miRNAs, tasiRNAs and natural antisense transcripts-generated small interfering RNAs (natsiRNAs) were identified and compared between libraries. In the leaf of OE lines, 15 known miRNAs increased in abundance and 9 miRNAs decreased in abundance, whereas in the root of OE lines, 2 known miRNAs increased in abundance and 9 miRNAs decreased in abundance. miRNAs with increased abundance in the leaf and root samples of both OE lines (miR158b and miR172a/b) were predicted to target mRNAs coding for Dof zinc finger protein and Apetala 2 (AP2) proteins, respectively. Furthermore, a significant change in the miR173-tasiRNAs-PPR/TPR network was observed in the leaves of both OE lines. CONCLUSION: In this study, the impact of high energy content on the sRNA profiles of Arabidopsis is reported. While the abundance of many stress-induced miRNAs is unaltered, the abundance of some miRNAs related to plant growth and development (miR172 and miR319) is elevated in the fast-growing lines. An induction of miR173-tasiRNAs-PPR/TPR network was also observed in the OE lines. In contrast, only few cis- and trans-natsiRNAs are altered in the fast-growing lines.published_or_final_versio