Tetrad analysis in plants and fungi finds large differences in gene conversion rates but no GC bias

GC-favouring gene conversion enables fixation of deleterious alleles, disturbs tests of natural selection and potentially explains both the evolution of recombination as well as the commonly reported intragenomic correlation between G+C content and recombination rate. In addition, gene conversion disturbs linkage disequilibrium, potentially affecting the ability to detect causative variants. However, the importance and generality of these effects is unresolved, not simply because direct analyses are technically challenging but also because previous within- and between-species discrepant results can be hard to appraise owing to methodological differences. Here we report results of methodologically uniform whole-genome sequencing of all tetrad products in Saccharomyces, Neurospora, Chlamydomonas and Arabidopsis. The proportion of polymorphic markers converted varies over three orders of magnitude between species (from 2% of markers converted in yeast to only ~0.005% in the two plants) with at least 87.5% of the variance in per tetrad conversion rates being between species. This is largely due to differences in recombination rate and median tract length. Despite three of the species showing a positive GC-recombination correlation, there is no significant net AT→GC conversion bias in any of the species, despite relatively high resolution in the two taxa (Saccharomyces and Neurospora) with relatively common gene conversion. The absence of a GC bias means that: (1) there should be no presumption that gene conversion is GC biased, or (2) that a GC-recombination correlation necessarily implies biased gene conversion, (3) K a/K s tests should be unaffected in these species and (4) it is unlikely that gene conversion explains the evolution of recombination. </p

An Edge Caching Strategy Based on User Speed and Content Popularity for Mobile Video Streaming

Mobile users’ demands to delay-sensitive video streaming media put forward new requirements for mobile networks, such as architecture optimization. Edge caching as a new paradigm is proposed to enhance the quality of service (QoS) for mobile users at the network edge. Due to the limited coverage of edge cache nodes, the frequent handoffs between base stations would aggravate network traffic overhead, resulting in a bad experience of high latency and service interruption when mobile users browse videos. This paper first proposes a three-layer mobile edge network architecture and applied edge caching to video streams to build an efficient caching system. Given the user’s mobility and low latency of mobile video streaming, we propose an edge caching strategy based on user speed and content popularity. Horizontally, the user’s speed affects the spanning area and the buffer size of the cache on edge; vertically, content popularity determines the priority of cached videos. Experimental results demonstrate that our caching strategy outperforms other schemes in terms of the average delay and the cache hit ratio in mobile video streaming scenes compared with the other three classic caching methods

A Threshold Proxy Re-Encryption Scheme for Secure IoT Data Sharing Based on Blockchain

The IoT devices deployed in various application scenarios will generate massive data with immeasurable value every day. These data often contain the user’s personal privacy information, so there is an imperative need to guarantee the reliability and security of IoT data sharing. We proposed a new encrypted data storing and sharing architecture by combining proxy re-encryption with blockchain technology. The consensus mechanism based on threshold proxy re-encryption eliminates dependence on the third-party central service providers. Multiple consensus nodes in the blockchain network act as proxy service nodes to re-encrypt data and combine converted ciphertext, and personal information will not be disclosed in the whole procedure. That eliminates the restrictions of using decentralized network to store and distribute private encrypted data safely. We implemented a lot of simulated experiments to evaluate the performance of the proposed framework. The results show that the proposed architecture can meet the extensive data access demands and increase a tolerable time latency. Our scheme is one of the essays to utilize the threshold proxy re-encryption and blockchain consensus algorithm to support IoT data sharing

Student perceptions toward virtual reality training in dental implant education

Objectives Both the shortage of professional teaching resources and the expensive dental implant supplies impede the effective training of dental undergraduate in implantology. Virtual reality (VR) technology may provide solutions to solve these problems. This pilot study was implemented to explore the usability and acceptance of a VR application in the training of dental implant among dental students at the Jinan University School of Stomatology. Methods We designed and developed a VR system with head-mounted displays (HMDs) to assist dental implant training. Undergraduate dental students were invited to experience a 30-minute “Introduction to dental implants” VR-HMDs training module. A total of 119 dental students participated the training. Firstly, the VR interactive training on dental implant was described, illustrated and practiced. Next, a system usability scale (SUS) survey was used to verify the usability and feasibility of the VR application on training dental students. Finally, the participants were given a questionnaire to provide their perceptions and feedback of the usefulness of the VR application for training dental implant skills. Results The SUS score was 82.00 ± 10.79, indicating a top 10 percentage ranking of the system’s usabilitys. The participants’ answers to the questionnaire reflected most of them exhibited strong interests in the VR system, with a tendency that the female students were more confident than the male in manipulating the VR system. The participants generally acknowledged the usefulness of VR dental implants, ranking VR value above the traditional laboratory operations, and a preference for using the VR system on learning other skills. They also gave valuable suggestions on VR dental implants for substantial improvement. However, some students were not strongly positive about the VR training in this study, the reason might lie in a more theoretical module was selected for testing, which impacted the students’ ratings. Conclusions In this study we revealed the feasibility and usability of VR applications on training dental implant among undergraduate dental students. This pilot study showed that the participants benefited from the dental implant VR training by practicing the skills repeatedly. The feedback from student participants affirmed the advantages and their acceptance of the VR application in dental education. Especially, the VR-based technology is highly conducive to clinical operating skills and surgical procedures-focused training in medical education, indicating that the VR system should be combined with the traditional practice approach in improving dental students’ practical abilities

Delayed wet season increases soil net N mineralization in a seasonally tropical forest

Seasonal precipitation regime plays a vital role in regulating nutrient dynamics in seasonally dry tropical forests. Present evidence suggests that not only wet season precipitation is increasing in the tropics of South China, but also that the wet season is occurring later. However, it is unclear how nutrient dynamics will respond to the projected precipitation regime changes. We assessed the impacts of altered seasonal precipitation on soil net N mineralization in a secondary tropical forest. Since 2013, by reducing throughfall and/or irrigating experimental plots, we delayed the wet season by two months from April–September to June–November (DW treatment) or increased mean annual precipitation by 25% in July and August (WW treatment). We measured soil net N mineralization rates and assessed soil microbial communities in January, April, August and November in 2015 and 2017. We found that a wetter wet season did not significantly affect soil microbes or net N mineralization rates, even in the mid-wet season (August) when soil water content in the WW treatment increased significantly. By contrast, a delayed wet season enhanced soil microbial biomass and altered microbial community structure, resulting in a two-fold increase in net N mineralization rates relative to controls in the early dry season (November). Structural equation modeling showed that the changes in net N mineralization during the early dry season were associated with altered soil microbial communities, dissolved organic N, and litterfall, which were all affected by enhanced soil water content. Our findings suggest that a delayed wet season could have a greater impact on N dynamics than increased precipitation during the wet season. Changes in the seasonal timing of rainfall might therefore influence the functioning of seasonally dry tropical forests

Redox-Responsive Polymer–Drug Conjugates Based on Doxorubicin and Chitosan Oligosaccharide‑<i>g</i>‑stearic Acid for Cancer Therapy

Here, a biodegradable polymer–drug conjugate of doxorubicin (DOX) conjugated with a stearic acid-grafted chitosan oligosaccharide (CSO-SA) was synthesized via disulfide linkers. The obtained polymer–drug conjugate DOX-SS-CSO-SA could self-assemble into nanosized micelles in aqueous medium with a low critical micelle concentration. The size of the micelles was 62.8 nm with a narrow size distribution. In reducing environments, the DOX-SS-CSO-SA could rapidly disassemble result from the cleavage of the disulfide linkers and release the DOX. DOX-SS-CSO-SA had high efficiency for cellular uptake and rapidly released DOX in reductive intracellular environments. <i>In vitro</i> antitumor activity tests showed that the DOX-SS-CSO-SA had higher cytotoxicity against DOX-resistant cells than free DOX, with reversal ability up to 34.8-fold. DOX-SS-CSO-SA altered the drug distribution <i>in vivo</i>, which showed selectively accumulation in tumor and reduced nonspecific accumulation in hearts. <i>In vivo</i> antitumor studies demonstrated that DOX-SS-CSO-SA showed efficient suppression on tumor growth and relieved the DOX-induced cardiac injury. Therefore, DOX-SS-CSO-SA is a potential drug delivery system for safe and effective cancer therapy

Combining Calcitonin and Procalcitonin and Rheumatoid Arthritis-Related Biomarkers Improve Diagnostic Outcomes in Early Rheumatoid Arthritis

Objective. To demonstrate whether procalcitonin (PCT) combined with calcitonin (CT) could provide additional diagnostic value to other clinically available rheumatoid arthritis- (RA-) related biomarkers in the early diagnosis of RA. Method. The blood samples aseptically collected by venipuncture were centrifuged within 1 hour and frozen at -80°C. PCT and CT levels were measured using electrochemiluminescence immunoassay (ECLIA) in 260 subjects (48 patients with early RA, 34 patients with established RA, 37 patients with systemic lupus erythematosus, 30 with osteoarthritis, 31 with gouty arthritis, and 80 healthy participants). Anti-cyclic citrullinated peptide (Anti-CCP) and anti-RA33 antibodies (Anti-RA33) were analyzed by ELISA. RF was detected by transmission immunoturbidimetry. Mann–Whitney U tests and Kruskal-Wallis tests compared differences among groups. Spearman’s rank correlation analysis determined the relationship between biomarkers. Receiver-operator characteristic (ROC) curves were generated, and diagnostic performance was assessed by area under the curve (AUC), as well as specificity, sensitivity, likelihood ratios (LR). Results. Median serum PCT concentrations were significantly higher (p<0.0001) in patients with early RA (0.065 ng/ml) when compared with healthy controls (0.024 ng/ml), and patients with osteoarthritis (0.025 ng/ml). When compared with gouty arthritis (GA) controls (0.072 ng/ml) and systemic lupus erythematosus (SLE) controls (0.093 ng/ml), median serum PCT concentrations were not significant in patients with early RA (0.065 ng/ml). Median serum CT concentrations were significantly lower (p<0.0001) in patients with early RA (0.880 pg/ml) compared with healthy controls (3.159 pg/ml), patients with SLE (2.480 pg/ml), and patients with GA (2.550 pg/ml). When compared with osteoarthritis controls (0.586 pg/ml), median serum CT concentrations were not significant in patients with early RA (0.880 pg/ml). ROC curve analysis comparing early RA with healthy controls demonstrated that the AUC of RF, anti-CCP, and anti-RA33 were 0.66, 0.73, and 0.64, respectively; the additions of PCT and CT further improved the diagnostic ability of early RA with the AUC of 0.97, 0.98, and 0.97, respectively (p<0.01). The sensitivities of RF, anti-CCP, and anti-RA33 for early RA were 33.33%, 44.74%, and 58.33%, respectively, and the additions of PCT and CT showed very high sensitivities of 83.33%, 92.11%, and 87.50%. The high-value groups of PCT moderately correlated with the anti-RA33 levels (r=0.417, p<0.05). CT had no significant correlation with disease duration, radiographic progression, or clinical/serological variables, such as ESR levels, CRP levels, RF, anti-CCP, and anti-RA33 levels in early RA. Conclusions. Serum PCT and CT combined with clinically available RA-related biomarkers could further improve the diagnostic efficiency of early RA

The architecture of intra-organism mutation rate variation in plants.

Given the disposability of somatic tissue, selection can favor a higher mutation rate in the early segregating soma than in germline, as seen in some animals. Although in plants intra-organismic mutation rate heterogeneity is poorly resolved, the same selectionist logic can predict a lower rate in shoot than in root and in longer-lived terminal tissues (e.g., leaves) than in ontogenetically similar short-lived ones (e.g., petals), and that mutation rate heterogeneity should be deterministic with no significant differences between biological replicates. To address these expectations, we sequenced 754 genomes from various tissues of eight plant species. Consistent with a selectionist model, the rate of mutation accumulation per unit time in shoot apical meristem is lower than that in root apical tissues in perennials, in which a high proportion of mutations in shoots are themselves transmissible, but not in annuals, in which somatic mutations tend not to be transmissible. Similarly, the number of mutations accumulated in leaves is commonly lower than that within a petal of the same plant, and there is no more heterogeneity in accumulation rates between replicate branches than expected by chance. High mutation accumulation in runners of strawberry is, we argue, the exception that proves the rule, as mutation transmission patterns indicate that runner has a restricted germline. However, we also find that in vitro callus tissue has a higher mutation rate (per unit time) than the wild-grown comparator, suggesting nonadaptive mutational "fragility". As mutational fragility does not obviously explain why the shoot-root difference varies with plant longevity, we conclude that some mutation rate variation between tissues is consistent with selectionist theory but that a mechanistic null of mutational fragility should be considered

Hesperetin, a Promising Dietary Supplement for Preventing the Development of Calcific Aortic Valve Disease

Background: No effective therapeutic agents for calcific aortic valve disease (CAVD) are available currently. Dietary supplementation has been proposed as a novel treatment modality for various diseases. As a flavanone, hesperetin is widely abundant in citrus fruits and has been proven to exert protective effects in multiple diseases. However, the role of hesperetin in CAVD remains unclear. Methods: Human aortic valve interstitial cells (VICs) were isolated from aortic valve leaflets. A mouse model of aortic valve stenosis was constructed by direct wire injury (DWI). Immunoblotting, immunofluorescence staining, and flow cytometry were used to investigate the roles of sirtuin 7 (Sirt7) and nuclear factor erythroid 2-related factor 2 (Nrf2) in hesperetin-mediated protective effects in VICs. Results: Hesperetin supplementation protected the mice from wire-injury-induced aortic valve stenosis; in vitro, hesperetin inhibited the lipopolysaccharide (LPS)-induced activation of NF-&kappa;B inflammatory cytokine secretion and osteogenic factors expression, reduced ROS production and apoptosis, and abrogated LPS-mediated injury to the mitochondrial membrane potential and the decline in the antioxidant levels in VICs. These benefits of hesperetin may have been obtained by activating Nrf2&ndash;ARE signaling, which corrected the dysfunctional mitochondria. Furthermore, we found that hesperetin could directly bind to Sirt7 and that the silencing of Sirt7 decreased the effects of hesperetin in VICs and potently abolished the ability of hesperetin to increase Nrf2 transcriptional activation. Conclusions: Our work demonstrates that hesperetin plays protective roles in the aortic valve through the Sirt7&ndash;Nrf2&ndash;ARE axis; thus, hesperetin might be a potential dietary supplement that could prevent the development of CAVD

Genomic analysis, trajectory tracking, and field surveys reveal sources and long-distance dispersal routes of wheat stripe rust pathogen in China

Identifying sources of phytopathogen inoculum and determining their contributions to disease outbreaks are essential for predicting disease development and establishing control strategies. Puccinia striiformis f. sp. tritici (Pst), the causal agent of wheat stripe rust, is an airborne fungal pathogen with rapid virulence variation that threatens wheat production through its long-distance migration. Because of wide variation in geographic features, climatic conditions, and wheat production systems, Pst sources and related dispersal routes in China are largely unclear. In the present study, we performed genomic analyses of 154 Pst isolates from all major wheat-growing regions in China to determine Pst population structure and diversity. Through trajectory tracking, historical migration studies, genetic introgression analyses, and field surveys, we investigated Pst sources and their contributions to wheat stripe rust epidemics. We identified Longnan, the Himalayan region, and the Guizhou Plateau, which contain the highest population genetic diversities, as the Pst sources in China. Pst from Longnan disseminates mainly to eastern Liupan Mountain, the Sichuan Basin, and eastern Qinghai; that from the Himalayan region spreads mainly to the Sichuan Basin and eastern Qinghai; and that from the Guizhou Plateau migrates mainly to the Sichuan Basin and the Cen-tral Plain. These findings improve our current understanding of wheat stripe rust epidemics in China and emphasize the need for managing stripe rust on a national scale