Metagenomic insight into the global dissemination of the antibiotic resistome

The global crisis in antimicrobial resistance continues to grow. Estimating the risks of antibiotic resistance transmission across habitats is hindered by the lack of data on mobility and habitat-specificity. Metagenomic samples of 6092 are analyzed to delineate the unique core resistomes from human feces and seven other habitats. This is found that most resistance genes (≈85%) are transmitted between external habitats and human feces. This suggests that human feces are broadly representative of the global resistome and are potentially a hub for accumulating and disseminating resistance genes. The analysis found that resistance genes with ancient horizontal gene transfer (HGT) events have a higher efficiency of transfer across habitats, suggesting that HGT may be the main driver for forming unique but partly shared resistomes in all habitats. Importantly, the human fecal resistome is historically different and influenced by HGT and age. The most important routes of cross-transmission of resistance are from the atmosphere, buildings, and animals to humans. These habitats should receive more attention for future prevention of antimicrobial resistance. The study will disentangle transmission routes of resistance genes between humans and other habitats in a One Health framework and can identify strategies for controlling the ongoing dissemination and antibiotic resistance

Ponatinib Activates an Inflammatory Response in Endothelial Cells via ERK5 SUMOylation

Ponatinib is a multi-targeted third generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukemia (CML) patients harboring the Abelson (Abl)-breakpoint cluster region (Bcr) T315I mutation. In spite of having superb clinical efficacy, ponatinib triggers severe vascular adverse events (VAEs) that significantly limit its therapeutic potential. On vascular endothelial cells (ECs), ponatinib promotes EC dysfunction and apoptosis, and inhibits angiogenesis. Furthermore, ponatinib-mediated anti-angiogenic effect has been suggested to play a partial role in systemic and pulmonary hypertension via inhibition of vascular endothelial growth factor receptor 2 (VEGFR2). Even though ponatinib-associated VAEs are well documented, their etiology remains largely unknown, making it difficult to efficiently counteract treatment-related adversities. Therefore, a better understanding of the mechanisms by which ponatinib mediates VAEs is critical. In cultured human aortic ECs (HAECs) treated with ponatinib, we found an increase in nuclear factor NF-kB/p65 phosphorylation and NF-kB activity, inflammatory gene expression, cell permeability, and cell apoptosis. Mechanistically, ponatinib abolished extracellular signal-regulated kinase 5 (ERK5) transcriptional activity even under activation by its upstream kinase mitogen-activated protein kinase kinase 5α (CA-MEK5α). Ponatinib also diminished expression of ERK5 responsive genes such as Krüppel-like Factor 2/4 (klf2/4) and eNOS. Because ERK5 SUMOylation counteracts its transcriptional activity, we examined the effect of ponatinib on ERK5 SUMOylation, and found that ERK5 SUMOylation is increased by ponatinib. We also found that ponatibib-mediated increased inflammatory gene expression and decreased anti-inflammatory gene expression were reversed when ERK5 SUMOylation was inhibited endogenously or exogenously. Overall, we propose a novel mechanism by which ponatinib up-regulates endothelial ERK5 SUMOylation and shifts ECs to an inflammatory phenotype, disrupting vascular homeostasis

Revisiting the concentration observations and source apportionment of atmospheric ammonia

While China’s Air Pollution Prevention and Control Action Plan on particulate matter since 2013 has reduced sulfate significantly, aerosol ammonium nitrate remains high in East China. As the high nitrate abundances are strongly linked with ammonia, reducing ammonia emissions is becoming increasingly important to improve the air quality of China. Although satellite data provide evidence of substantial increases in atmospheric ammonia concentrations over major agricultural regions, long-term surface observation of ammonia concentrations are sparse. In addition, there is still no consensus on whether agricultural or non-agricultural emissions dominate the urban ammonia budget. Identifying the ammonia source by nitrogen isotope helps in designing a mitigation strategy for policymakers, but existing methods have not been well validated. Revisiting the concentration measurements and identifying source apportionment of atmospheric ammonia is thus an essential step towards reducing ammonia emissions

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.We thank W. Liu and L. Xu from the Huazhen Laboratory Animal Breeding Centre for helping in the collection of monkey tissues, D. Zhu and H. Li from the Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) for technical help, G. Guo and H. Sun from Zhejiang University for providing HCL and MCA gene expression data matrices, G. Dong and C. Liu from BGI Research, and X. Zhang, P. Li and C. Qi from the Guangzhou Institutes of Biomedicine and Health for experimental advice or providing reagents. This work was supported by the Shenzhen Basic Research Project for Excellent Young Scholars (RCYX20200714114644191), Shenzhen Key Laboratory of Single-Cell Omics (ZDSYS20190902093613831), Shenzhen Bay Laboratory (SZBL2019062801012) and Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011). In addition, L.L. was supported by the National Natural Science Foundation of China (31900466), Y. Hou was supported by the Natural Science Foundation of Guangdong Province (2018A030313379) and M.A.E. was supported by a Changbai Mountain Scholar award (419020201252), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030502), a Chinese Academy of Sciences–Japan Society for the Promotion of Science joint research project (GJHZ2093), the National Natural Science Foundation of China (92068106, U20A2015) and the Guangdong Basic and Applied Basic Research Foundation (2021B1515120075). M.L. was supported by the National Key Research and Development Program of China (2021YFC2600200).S

Health impacts of parental migration on left-behind children and adolescents: a systematic review and meta-analysis.

BACKGROUND: Globally, a growing number of children and adolescents are left behind when parents migrate. We investigated the effect of parental migration on the health of left behind-children and adolescents in low-income and middle-income countries (LMICs). METHODS: For this systematic review and meta-analysis we searched MEDLINE, Embase, CINAHL, the Cochrane Library, Web of Science, PsychINFO, Global Index Medicus, Scopus, and Popline from inception to April 27, 2017, without language restrictions, for observational studies investigating the effects of parental migration on nutrition, mental health, unintentional injuries, infectious disease, substance use, unprotected sex, early pregnancy, and abuse in left-behind children (aged 0-19 years) in LMICs. We excluded studies in which less than 50% of participants were aged 0-19 years, the mean or median age of participants was more than 19 years, fewer than 50% of parents had migrated for more than 6 months, or the mean or median duration of migration was less than 6 months. We screened studies using systematic review software and extracted summary estimates from published reports independently. The main outcomes were risk and prevalence of health outcomes, including nutrition (stunting, wasting, underweight, overweight and obesity, low birthweight, and anaemia), mental health (depressive disorder, anxiety disorder, conduct disorders, self-harm, and suicide), unintentional injuries, substance use, abuse, and infectious disease. We calculated pooled risk ratios (RRs) and standardised mean differences (SMDs) using random-effects models. This study is registered with PROSPERO, number CRD42017064871. FINDINGS: Our search identified 10 284 records, of which 111 studies were included for analysis, including a total of 264 967 children (n=106 167 left-behind children and adolescents; n=158 800 children and adolescents of non-migrant parents). 91 studies were done in China and focused on effects of internal labour migration. Compared with children of non-migrants, left-behind children had increased risk of depression and higher depression scores (RR 1·52 [95% CI 1·27-1·82]; SMD 0·16 [0·10-0·21]), anxiety (RR 1·85 [1·36-2·53]; SMD 0·18 [0·11-0·26]), suicidal ideation (RR 1·70 [1·28-2·26]), conduct disorder (SMD 0·16 [0·04-0·28]), substance use (RR 1·24 [1·00-1·52]), wasting (RR 1·13 [1·02-1·24]) and stunting (RR 1·12 [1·00-1·26]). No differences were identified between left-behind children and children of non-migrants for other nutrition outcomes, unintentional injury, abuse, or diarrhoea. No studies reported outcomes for other infectious diseases, self-harm, unprotected sex, or early pregnancy. Study quality varied across the included studies, with 43% of studies at high or unclear risk of bias across five or more domains. INTERPRETATION: Parental migration is detrimental to the health of left-behind children and adolescents, with no evidence of any benefit. Policy makers and health-care professionals need to take action to improve the health of these young people. FUNDING: Wellcome Trust

A Method for Long-Term Target Anti-Interference Tracking Combining Deep Learning and CKF for LARS Tracking and Capturing

Autonomous underwater vehicles (AUV) recycling in an underwater environment is particularly challenging due to the continuous exploitation of marine resources. AUV recycling via visual technology is the primary method. However, the current visual technology is limited by harsh sea conditions and has problems, such as poor tracking and detection. To solve these problems, we propose a long-term target anti-interference tracking (LTAT) method, which integrates Siamese networks, You Only Look Once (YOLO) networks and online learning ideas. Meanwhile, we propose using the cubature Kalman filter (CKF) for optimization and prediction of the position. We constructed a launch and recovery system (LARS) tracking and capturing the AUV. The system consists of the following parts: First, images are acquired via binocular cameras. Next, the relative position between the AUV and the end of the LARS was estimated based on the pixel positions of the tracking AUV feature points and binocular camera data. Finally, using a discrete proportion integration differentiation (PID) method, the LARS is controlled to capture the moving AUV via a CKF-optimized position. To verify the feasibility of our proposed system, we used the robot operating system (ROS) platform and Gazebo software to simulate the system for experiments and visualization. The experiment demonstrates that in the tracking process when the AUV makes a sinusoidal motion with an amplitude of 0.2 m in the three-dimensional space and the relative distance between the AUV and LARS is no more than 1 m, the estimated position error of the AUV does not exceed 0.03 m. In the capturing process, the final capturing error is about 28 mm. Our results verify that our proposed system has high robustness and accuracy, providing the foundation for future AUV recycling research

Effect of Cold Pressor Test on Reaction Time

An article that appeared in JASS, issue 2014The purpose of this study was to examine variation in reaction time when a Cold Pressor Test (CPT) was administered. The three minute CPT was conducted in attempt to increase a person’s sympathetic response. Heart rate and blood pressure measurements were recorded throughout the test to accurately monitor participant’s response. In the study, the CPT was paired with an audio reaction time test conducted during the first and third minute of the experiment. The recorded measurements were then compared to the subjects’ baseline heart rate, blood pressure, and reaction time to determine statistical significance. It was found that average initial heart rate increased (n=37, p=6.14E-7<0.05), however the average mean arterial blood pressure (MABP) showed no significant change, thus leading to inconclusiveness in the degree of sympathetic activation due to the CPT. Compared to the average reaction time in room temperature water, the average reaction time during the cold pressor test decreased (n=37, p=0.0307<0.05), suggesting that the CPT had an effect on the reaction time of the individual. Further studies that also increase the sympathetic response could be conducted in order to allow for a better comparison between sympathetic response and reaction time

Secure Cloud-Aided Approximate Nearest Neighbor Search on High-Dimensional Data

As one fundamental data-mining problem, ANN (approximate nearest neighbor search) is widely used in many industries including computer vision, information retrieval, and recommendation system. $LSH$ (Local sensitive hashing) is one of the most popular hash-based approaches to solve ANN problems. However, the efficiency of operating $LSH$ needs to be improved, as the operations of $LSH$ often involve resource-consuming matrix operations and high-dimensional large-scale datasets. Meanwhile, for resource-constrained devices, this problem becomes more serious. One way to handle this problem is to outsource the heavy computing of high-dimensional large-scale data to cloud servers. However, when a cloud server responsible for computing tasks is untrustworthy, some security issues may arise. In this study, we proposed a cloud server-aided $LSH$ scheme and the application model. This scheme can perform the $LSH$ efficiently with the help of a cloud server and guarantee the privacy of the client&#x2019;s information. And, in order to identify the improper behavior of the cloud server, we also provide a verification method to check the results returned from the cloud server. Meanwhile, for the implementation of this scheme on resource-constrained devices, we proposed a model for the real application of this scheme. To verify the efficiency and correctness of the proposed scheme, theoretical analysis and experiments are conducted. The results of experiments and theoretical analysis indicate that the proposed scheme is correct, verifiable, secure and efficient