A two-sample mendelian randomization study of atherosclerosis and dementia

The causality between atherosclerosis and dementia remains unclear. This study aimed to explore the causal effect of atherosclerosis related indicators on dementia risk based on two-sample Mendelian randomization (MR) using summary statistics of genome-wide association studies (GWASs). The inverse variance weighted (IVW) method was performed as the main analysis, supplemented by different sensitivity analyses. Suggestive evidence indicated that peripheral arterial disease (PAD) (odds ratio (OR): 0.864, 95% confidence interval (CI): 0.797–0.937), coronary atherosclerosis (CoAS) (OR: 0.927, 95% CI: 0.860–0.998) and atherosclerosis, excluding cerebral, coronary, and PAD (ATHSCLE) (OR: 0.812, 95% CI: 0.725–0.909) were inversely associated with the risk of AD. The sensitivity analysis confirmed a suggestive reverse effect of ATHSCLE on the risk of frontotemporal dementia (FTD) (OR, 0.812, 95% CI, 0.725–0.909). Findings provide suggestive evidence that PAD, CoAS, and ATHSCLE might be associated with the risk of AD or FTD, which requires further exploration in larger samples

Towards Target-Driven Visual Navigation in Indoor Scenes via Generative Imitation Learning

We present a target-driven navigation system to improve mapless visual navigation in indoor scenes. Our method takes a multi-view observation of a robot and a target as inputs at each time step to provide a sequence of actions that move the robot to the target without relying on odometry or GPS at runtime. The system is learned by optimizing a combinational objective encompassing three key designs. First, we propose that an agent conceives the next observation before making an action decision. This is achieved by learning a variational generative module from expert demonstrations. We then propose predicting static collision in advance, as an auxiliary task to improve safety during navigation. Moreover, to alleviate the training data imbalance problem of termination action prediction, we also introduce a target checking module to differentiate from augmenting navigation policy with a termination action. The three proposed designs all contribute to the improved training data efficiency, static collision avoidance, and navigation generalization performance, resulting in a novel target-driven mapless navigation system. Through experiments on a TurtleBot, we provide evidence that our model can be integrated into a robotic system and navigate in the real world. Videos and models can be found in the supplementary material.Comment: 11 pages, accepted by IEEE Robotics and Automation Letter

Reinforcement Learning-based Visual Navigation with Information-Theoretic Regularization

To enhance the cross-target and cross-scene generalization of target-driven visual navigation based on deep reinforcement learning (RL), we introduce an information-theoretic regularization term into the RL objective. The regularization maximizes the mutual information between navigation actions and visual observation transforms of an agent, thus promoting more informed navigation decisions. This way, the agent models the action-observation dynamics by learning a variational generative model. Based on the model, the agent generates (imagines) the next observation from its current observation and navigation target. This way, the agent learns to understand the causality between navigation actions and the changes in its observations, which allows the agent to predict the next action for navigation by comparing the current and the imagined next observations. Cross-target and cross-scene evaluations on the AI2-THOR framework show that our method attains at least a $10\%$ improvement of average success rate over some state-of-the-art models. We further evaluate our model in two real-world settings: navigation in unseen indoor scenes from a discrete Active Vision Dataset (AVD) and continuous real-world environments with a TurtleBot.We demonstrate that our navigation model is able to successfully achieve navigation tasks in these scenarios. Videos and models can be found in the supplementary material.Comment: 11 pages, corresponding author: Kai Xu ([email protected]) and Jun Wang ([email protected]

Arginine Alters miRNA Expression Involved in Development and Proliferation of Rat Mammary Tissue

This study was designed to determine the effects of dietary arginine on development and proliferation in rat mammary tissue through changes in miRNA profiles. Twelve pregnant Wistar rats were allocated randomly to two groups. A basal diet containing arginine or the control diet containing glutamate on an equal nitrogen basis as the arginine supplemented diet were used. The experiment included a pre-experimental period of four days before parturition and an experimental period of 17 days after parturition. Mammary tissue was collected for histology, RNA extraction and high-throughput sequencing analysis. The greater mammary acinar area indicated that arginine supplementation enhanced mammary tissue development (p < 0.01). MicroRNA profiling indicated that seven miRNA (miR-206-3p, miR-133a-5p, miR-133b-3p, miR-1-3p, miR-133a-3p, miR-1b and miR-486) were differentially expressed in response to Arginine when compared with the glutamate-based control group. In silico gene ontology enrichment and KEGG pathway analysis revealed between 240 and 535 putative target genes among the miRNA. Further verification by qPCR revealed concordance with the differential expression from the sequencing results: 17 of 28 target genes were differentially expressed (15 were highly expressed in arginine and 2 in control) and 11 target genes did not have significant difference in expression. In conclusion, our study suggests that arginine may potentially regulate the development of rat mammary glands through regulating miRNAs

MicroRNA-275 and its target vitellogenin-2 are crucial in ovary development and blood digestion of Haemaphysalis longicornis

Background: The hard tick Haemaphysalis longicornis is widely distributed in eastern Asia, New Zealand and Australia and is considered the major vector of Theileria and Babesia, harmful parasites to humans and animals. Female ticks need successful blood meals to complete the life-cycle. Therefore, elucidation of the underlying molecular mechanisms of H. longicornis development and reproduction is considered important for developing control strategies against the tick and tick-borne pathogens. Methods: Luciferase assays were used to identify the targets of micro RNA miR-275 in vitro. RNAi of Vitellogenin (Vg) was used in phenotype rescue experiments of ticks with miR-275 inhibition, and these analyses were used to identify the authentic target of miR-275 in vivo. The expression of miR-275 in different tissues and developmental stages of ticks was assessed by real-time PCR. To elucidate the functions of miR-275 in female ticks, we injected a miR-275 antagomir into female ticks and observed the phenotypic changes. Statistical analyses were performed with GraphPad5 using Student’s t-test. Results: In this study, we identified Vg-2 as an authentic target of miR-275 both in vitro and in vivo by luciferase assays and phenotype rescue experiments. miR-275 plays the regulatory role in a tissue-specific manner and differentially in developmental stages. Silencing of miR-275 resulted in blood digestion problems, substantially impaired ovary development and significantly reduced egg mass (P < 0.0001). Furthermore, RNAi silencing of Vg-2 not only impacted the blood meal uptake (P < 0.05) but also the egg mass (P < 0.05). Significant rescue was observed in miR-275 knockout ticks when RNAi was applied to Vg-2. Conclusion: To our knowledge, this study is the first demonstration that miR-275 targets Vg-2 in H. longicornis and regulates the functions of blood digestion and ovary development. These findings improve the molecular understanding of tick development and reproduction

Vascular endothelial growth factor and the risk of venous thromboembolism: A genetic correlation and two-sample Mendelian randomization study

Background: The relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE. Methods: Summary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score regression (LDSC) and five robust MR analytical approaches were conducted to estimate the genetic correlations and causal inference. The MR-Egger intercept, Cochran’s Q, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on outcomes. Notably, replication analyses were performed using different subgroups of VTE. Results: LDSC failed to identify genetic correlations between VEGF and VTE. Based on 9 SNPs, the circulating VEGF level was positively related to the risk of VTE using inverse variance weighting (IVW) method (odds ratio (OR) = 1.064, 95 % confidence interval (CI), 1.009 – 1.122). Reverse MR analyses showed that genetic liability for VTE was not associated with increased VEGF level (β = -0.021, 95 % CI, -0.087-0.045). Pleiotropy-robust methods indicated no bias in any estimates. Conclusions: Our findings failed to detect coheritability between VEGF and VTE. The suggestive positive effect of the higher VEGF level on the VTE risk may have clinical implications, suggesting that VEGF as a possible predictor and therapeutic target for VTE prevention need to be further warranted

Using Maxwell’s Theory to model and quantify the fracture evolution of cyclothymic deposition phosphate rock

The evolution and stability of fracturing in the cyclothymic deposition of phosphate rocks are strongly affected by the viscoelasticity and structural form of the rock-forming minerals. Presently, there is no standardized method that has been widely accepted to accurately quantify the elastic-plastic deformation and fracturing of such striped structural rock nor reflect the role of the different lithogenous minerals in phosphate rocks when subjected to viscoelastic strain loading. In this study, integrated mathematical equations were formulated for modelling the mechanical and fracture behaviour of cyclothymic deposition in structured phosphate rocks. These constitutive equations were developed based on Maxwell’s Theory after the elastic modulus and damping coefficient of the rock-forming mineral from the mechanical testing were substituted into the derived-equations. In these new models, the apatite stripes and dolomite stripes were incorporated into the transverse isotropic model through the analysis of structural characteristics of the phosphate rock. Through experimental validation, the response curves of the creep and stress relaxation tests were found to be consistent with the deformation curves generated by modelling using the mathematical equations. Overall, the formulated model along with the corresponding equations was found to exhibit good applicability properties to describe phosphate’s mechanical and fracture behaviour under low horizontal compressive stresses. In the study, the creep mechanism in phosphate rocks were satisfactorily analysed from the angles of microscopic morphology, cracks evolution, and inter-crystalline strength. The hard brittle apatite was found to be surrounded and separated by high creep variant dolomite. Furthermore, the analysis showed that dolomite crystals possessing high creep properties dominated the distribution and evolution of secondary structures in the phosphate rock, under the condition of long-term low-stress loading

Avian Influenza (H5N1) Virus in Waterfowl and Chickens, Central China

In 2004, 3 and 4 strains of avian influenza virus (subtype H5N1) were isolated from waterfowl and chickens, respectively, in central People’s Republic of China. Viral replication and pathogenicity were evaluated in chickens, quails, pigeons, and mice. We analyzed the sequences of the hemagglutinin and neuraminidase genes of the isolates and found broad diversity among them

In vitro expression and analysis of the 826 human G protein-coupled receptors

ABSTRACT G protein-coupled receptors (GPCRs) are involved in all human physiological systems where they are responsible for transducing extracellular signals into cells. GPCRs signal in response to a diverse array of stimuli including light, hormones, and lipids, where these signals affect downstream cascades to impact both health and disease states. Yet, despite their importance as therapeutic targets, detailed molecular structures of only 30 GPCRs have been determined to date. A key challenge to their structure determination is adequate protein expression. Here we report the quantification of protein expression in an insect cell expression system for all 826 human GPCRs using two different fusion constructs. Expression characteristics are analyzed in aggregate and among each of the five distinct subfamilies. These data can be used to identify trends related to GPCR expression between different fusion constructs and between different GPCR families, and to prioritize lead candidates for future structure determination feasibility