Clades of huge phages from across Earth's ecosystems.

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems

Closely related Lak megaphages replicate in the microbiomes of diverse animals.

Lak phages with alternatively coded ∼540 kbp genomes were recently reported to replicate in Prevotella in microbiomes of humans that consume a non-Western diet, baboons, and pigs. Here, we explore Lak phage diversity and broader distribution using diagnostic polymerase chain reaction and genome-resolved metagenomics. Lak phages were detected in 13 animal types, including reptiles, and are particularly prevalent in pigs. Tracking Lak through the pig gastrointestinal tract revealed significant enrichment in the hindgut compared to the foregut. We reconstructed 34 new Lak genomes, including six curated complete genomes, all of which are alternatively coded. An anomalously large (∼660 kbp) complete genome reconstructed for the most deeply branched Lak from a horse microbiome is also alternatively coded. From the Lak genomes, we identified proteins associated with specific animal species; notably, most have no functional predictions. The presence of closely related Lak phages in diverse animals indicates facile distribution coupled to host-specific adaptation

Mapping Webs of Information, Conversation, and Social Connections: Evaluating the Mechanics of Collaborative Adaptive Management in the Sierra Nevada Forests

Managing within social-ecological systems at the landscape scale, such as in the national forests of the Sierra Nevada of California, is challenging to natural resource managers (e.g. the U.S. Forest Service) due to the uncertainties in natural processes and the complexities in social dynamics. Collaborative adaptive management (CAM) has been recently adopted as a viable strategy to diminish uncertainties in natural processes through iterative policy experimentations and adaptations, as well as to overcome conflicting values and goals among diverse environmental stakeholders through fostering and facilitating collaborations. While many CAM studies have focused on evaluating the management impact on natural systems and processes, few have examined the social engagements and dynamics of management itself. To address this knowledge gap, I examined the various social engagements in CAM, particularly the flow of information products, dialogues in public meetings, and social connections among participants, based on my research case study—the Sierra Nevada Adaptive Management Project (SNAMP). SNAMP began in 2005 in response to the USDA National Forest Service's 2004 Sierra Nevada Forest Plan Amendment calls for managing the forest using the best information available to protect forests and homes. The participants in the project can be sorted into three primary categories of environmental stakeholders: federal and state environmental agencies, the public and environmental advocacy groups, and university scientists. The project studies the impact of forest fuel reduction treatment on forest health, fire mitigation and prevention, wildlife, and water quality and quantity at two study sites: Last Chance in the northern region of the Sierra forests at Sugar Pine in the southern region. The primary strategies and methods for fostering partnership and facilitating collaboration among the diverse participants are producing science information and making it transparent and publicly accessible, as well as facilitating discussions about such research and management results in public meetings. To evaluate the effectiveness of CAM in the case of SNAMP, I used a mixed-methods research approach (i.e. citation analysis, web analytics, content analysis, self-organizing maps, social network analysis), by leveraging available information technologies and tools, to characterize and analyze the flow of digital information products, the outcomes of facilitated discussions in SNAMP public meetings, and the resilience of the social networks in SNAMP. Some of the interesting findings include: 1) Scientific knowledge products, in the form of peer-reviewed journal publications, contributed to knowledge transfer between scientists and environmental managers; 2) facilitated discussions helped environmental stakeholders to stay engaged on the important administrative and research topics through time; 3) the social networks experienced turbulence but remained resilient due to the existence of a committed and consistent core group of environmental stakeholders that represent diverse backgrounds and interests. As the picture of how information, conversation, and social connections contributed to the success of CAM emerged, my dissertation provides recommendations to natural resource managers on how to improve in these areas for future implementations of CAM

Mapping Webs of Information, Conversation, and Social Connections: Evaluating the Mechanics of Collaborative Adaptive Management in the Sierra Nevada Forests

Managing within social-ecological systems at the landscape scale, such as in the national forests of the Sierra Nevada of California, is challenging to natural resource managers (e.g. the U.S. Forest Service) due to the uncertainties in natural processes and the complexities in social dynamics. Collaborative adaptive management (CAM) has been recently adopted as a viable strategy to diminish uncertainties in natural processes through iterative policy experimentations and adaptations, as well as to overcome conflicting values and goals among diverse environmental stakeholders through fostering and facilitating collaborations. While many CAM studies have focused on evaluating the management impact on natural systems and processes, few have examined the social engagements and dynamics of management itself. To address this knowledge gap, I examined the various social engagements in CAM, particularly the flow of information products, dialogues in public meetings, and social connections among participants, based on my research case study--the Sierra Nevada Adaptive Management Project (SNAMP).SNAMP began in 2005 in response to the USDA National Forest Service's 2004 Sierra Nevada Forest Plan Amendment calls for managing the forest using the best information available to protect forests and homes. The participants in the project can be sorted into three primary categories of environmental stakeholders: federal and state environmental agencies, the public and environmental advocacy groups, and university scientists. The project studies the impact of forest fuel reduction treatment on forest health, fire mitigation and prevention, wildlife, and water quality and quantity at two study sites: Last Chance in the northern region of the Sierra forests at Sugar Pine in the southern region. The primary strategies and methods for fostering partnership and facilitating collaboration among the diverse participants are producing science information and making it transparent and publicly accessible, as well as facilitating discussions about such research and management results in public meetings. To evaluate the effectiveness of CAM in the case of SNAMP, I used a mixed-methods research approach (i.e. citation analysis, web analytics, content analysis, self-organizing maps, social network analysis), by leveraging available information technologies and tools, to characterize and analyze the flow of digital information products, the outcomes of facilitated discussions in SNAMP public meetings, and the resilience of the social networks in SNAMP. Some of the interesting findings include: 1) Scientific knowledge products, in the form of peer-reviewed journal publications, contributed to knowledge transfer between scientists and environmental managers; 2) facilitated discussions helped environmental stakeholders to stay engaged on the important administrative and research topics through time; 3) the social networks experienced turbulence but remained resilient due to the existence of a committed and consistent core group of environmental stakeholders that represent diverse backgrounds and interests. As the picture of how information, conversation, and social connections contributed to the success of CAM emerged, my dissertation provides recommendations to natural resource managers on how to improve in these areas for future implementations of CAM

The Relationship Between Filial Expectations and Depressive Symptoms in Chinese Older Adults: The Mediating Role of Intergenerational Social Support

This study examined the relationship between filial expectations and depressive symptoms in Chinese older adults and the mediating role of intergenerational social support. A survey was administered to 310 people (age = 70.42 +/- 6.24 years; male/female = 174/136; years of schooling = 7.71 +/- 2.53) aged 60 years and above. The survey included the Geriatric Depression Scale, the Parent-Adult Child Social Support Questionnaire, and the Filial Piety Expectation Scale. (1) Filial expectations and intergenerational social support were negatively correlated with depressive symptoms, while intergenerational social support was positively correlated with filial expectations. (2) A mediation analysis showed that the impact of filial expectations on depressive symptoms was partly mediated by receiving intergenerational social support. (3) The indirect effects of filial expectations on depressive symptoms through receiving intergenerational social support were stronger when parents provided less intergenerational social support. Filial expectations of parents influenced depressive symptoms by affecting the intergenerational social support received from their adult children. This study has important implications for improving the physical and mental health of older adults

Energy and Operation Characteristics of Electric Excavator With Innovative Hydraulic-Electric Dual Power Drive Boom System

In the existing electric excavators, the energy efficiency of the hydraulic system is less than 30% due to a large amount of throttling loss and waste of potential energy. In order to improve excavator energy efficiency, an electric excavator scheme using a hydraulic-electric dual-power drive boom system is proposed. A linear actuator, including electro-mechanical unit and hydraulic unit, was adopted in the boom system. The boom velocity is controlled by the electro-mechanical unit instead of hydraulic valve to reduce throttling loss. The non-rod chamber of the linear actuator is connected to a hydraulic accumulator to reutilize boom gravitational potential energy. In addition, when the boom and other devices are operated together, the throttling loss caused by load difference of multi-actuators can be reduced because the linear actuator can compensate for the pump pressure. The working principle, control strategy, and characteristics of the proposed electric excavator were analyzed through theory and experiments. The results show that the proposed system can reduce throttling loss and efficiently reutilize the boom gravitational potential energy. During boom lifting and lowering process, the reutilization rate of the boom gravitational potential energy is 67.6%, and the energy consumption is reduced by 66.1%. During land levelling process, the throttling loss of the electric excavator is reduced by 49.6% and the energy consumption is reduced by 38.1%. The research results will provide new methods for the electrification of construction machinery

Cisplatin-resistant HepG2 cell-derived exosomes transfer cisplatin resistance to cisplatin-sensitive cells in HCC

Backgrounds Cancer cell resistance to chemotherapy drugs such as Gemcitabine, Oxaliplatin, Cisplatin, Doxorubicin, and 5-fluorouracil account for the main reason of chemotherapy failure for HCC patients, especially for those with advanced HCC or metastasis patients. This emerging resistance limits the effectiveness and clinical application of these chemotherapy drugs. Previous studies reported that drug-resistant tumor cell-derived exosomes could transfer their resistance property to tumor sensitive cells in some cancer, including lung and gastric cancer. This study sought to explore whether HepG2/DDP cell-derived exosomes transmit cisplatin (DDP) resistance to HepG2 and other HCC sensitive cells, and provide considerable guidance for HCC nursing with Cisplatin DDP clinically. Methods The HepG2 DDP-resistant cell line (HepG2/DDP) was established, and the exosomes from both HepG2/DDP and HepG2 cells were isolated and named ES-2, ES-1, respectively. HepG2 or SMMC-7721 or Huh7 cells were treated with DDP or DDP + ES-2, and HepG2/DDP cells were treated with ES-1. Then, the activation of drug resistance via HepG2/DDP exosomes transfer to HepG2, SMMC-7721 and Huh7 cells were assessed by cell viability assay and ROS formation. Moreover, the relative expression of P-glycoprotein (P-gp) was measured by western blot analysis. Results HepG2/DDP cell-derived exosomes were successfully isolated from cisplatin-resistant HepG2 cells, and named ES-2. Cell viability of HepG2 or SMMC-7721 or Huh7 cells treated with DDP + ES-2 was enhanced compared with that of DDP treatment group. Also, the concentration of ROS generated in cells under DDP or DDP + ES-2 treatment was strongly increased compared with that of control, although the concentration of ROS was clearly smaller in DDP + ES-2 treatment group compared with DDP treatment. At the same time, the expression of P-gp was upregulated on the ES-2 surface. Conclusion The results mentioned above clarified that HepG2/DDP cell-derived exosomes conferred cisplatin resistance to HepG2 and other HCC cell lines, and provided a new significance for improving the effectiveness of DDP in treating HCC

Diverse ATPase Proteins in Mobilomes Constitute a Large Potential Sink for Prokaryotic Host ATP.

Prokaryote mobilome genomes rely on host machineries for survival and replication. Given that mobile genetic elements (MGEs) derive their energy from host cells, we investigated the diversity of ATP-utilizing proteins in MGE genomes to determine whether they might be associated with proteins that could suppress related host proteins that consume energy. A comprehensive search of 353 huge phage genomes revealed that up to 9% of the proteins have ATPase domains. For example, ATPase proteins constitute ∼3% of the genomes of Lak phages with ∼550 kbp genomes that occur in the microbiomes of humans and other animals. Statistical analysis shows the number of ATPase proteins increases linearly with genome length, consistent with a large sink for host ATP during replication of megaphages. Using metagenomic data from diverse environments, we found 505 mobilome proteins with ATPase domains fused to diverse functional domains. Among these composite ATPase proteins, 61.6% have known functional domains that could contribute to host energy diversion during the mobilome infection cycle. As many have domains that are known to interact with nucleic acids and proteins, we infer that numerous ATPase proteins are used during replication and for protection from host immune systems. We found a set of uncharacterized ATPase proteins with nuclease and protease activities, displaying unique domain architectures that are energy intensive based on the presence of multiple ATPase domains. In many cases, these composite ATPase proteins genomically co-localize with small proteins in genomic contexts that are reminiscent of toxin-antitoxin systems and phage helicase-antibacterial helicase systems. Small proteins that function as inhibitors may be a common strategy for control of cellular processes, thus could inspire future biochemical experiments for the development of new nucleic acid and protein manipulation tools, with diverse biotechnological applications

An Overview of Meta-Analyses of Danhong Injection for Unstable Angina

Objective. To systematically collect evidence and evaluate the effects of Danhong injection (DHI) for unstable angina (UA). Methods. A comprehensive search was conducted in seven electronic databases up to January 2015. The methodological and reporting quality of included studies was assessed by using AMSTAR and PRISMA. Result. Five articles were included. The conclusions suggest that DHI plus conventional medicine treatment was effective for UA pectoris treatment, could alleviate symptoms of angina and ameliorate electrocardiograms. Flaws of the original studies and systematic reviews weaken the strength of evidence. Limitations of the methodology quality include performing an incomprehensive literature search, lacking detailed characteristics, ignoring clinical heterogeneity, and not assessing publication bias and other forms of bias. The flaws of reporting systematic reviews included the following: not providing a structured summary, no standardized search strategy. For the pooled findings, researchers took statistical heterogeneity into consideration, but clinical and methodology heterogeneity were ignored. Conclusion. DHI plus conventional medicine treatment generally appears to be effective for UA treatment. However, the evidence is not hard enough due to methodological flaws in original clinical trials and systematic reviews. Furthermore, rigorous designed randomized controlled trials are also needed. The methodology and reporting quality of systematic reviews should be improved

Vitamin interdependencies predicted by metagenomics-informed network analyses and validated in microbial community microcosms

Metagenomic or metabarcoding data are often used to predict microbial interactions in complex communities, but these predictions are rarely explored experimentally. Here, we use an organism abundance correlation network to investigate factors that control community organization in mine tailings-derived laboratory microbial consortia grown under dozens of conditions. The network is overlaid with metagenomic information about functional capacities to generate testable hypotheses. We develop a metric to predict the importance of each node within its local network environments relative to correlated vitamin auxotrophs, and predict that a Variovorax species is a hub as an important source of thiamine. Quantification of thiamine during the growth of Variovorax in minimal media show high levels of thiamine production, up to 100 mg/L. A few of the correlated thiamine auxotrophs are predicted to produce pantothenate, which we show is required for growth of Variovorax, supporting that a subset of vitamin-dependent interactions are mutualistic. A Cryptococcus yeast produces the B-vitamin pantothenate, and co-culturing with Variovorax leads to a 90-130-fold fitness increase for both organisms. Our study demonstrates the predictive power of metagenome-informed, microbial consortia-based network analyses for identifying microbial interactions that underpin the structure and functioning of microbial communities