The Yeast GSK-3 Homologue Mck1 Is a Key Controller of Quiescence Entry and Chronological Lifespan.

Upon starvation for glucose or any other core nutrient, yeast cells exit from the mitotic cell cycle and acquire a set of G0-specific characteristics to ensure long-term survival. It is not well understood whether or how cell cycle progression is coordinated with the acquisition of different G0-related features during the transition to stationary phase (SP). Here, we identify the yeast GSK-3 homologue Mck1 as a key regulator of G0 entry and reveal that Mck1 acts in parallel to Rim15 to activate starvation-induced gene expression, the acquisition of stress resistance, the accumulation of storage carbohydrates, the ability of early SP cells to exit from quiescence, and their chronological lifespan. FACS and microscopy imaging analyses indicate that Mck1 promotes mother-daughter cell separation and together with Rim15, modulates cell size. This indicates that the two kinases coordinate the transition-phase cell cycle, cell size and the acquisition of different G0-specific features. Epistasis experiments place MCK1, like RIM15, downstream of RAS2 in antagonising cell growth and activating stress resistance and glycogen accumulation. Remarkably, in the ras2∆ cells, deletion of MCK1 and RIM15 together, compared to removal of either of them alone, compromises respiratory growth and enhances heat tolerance and glycogen accumulation. Our data indicate that the nutrient sensor Ras2 may prevent the acquisition of G0-specific features via at least two pathways. One involves the negative regulation of the effectors of G0 entry such as Mck1 and Rim15, while the other likely to involve its functions in promoting respiratory growth, a phenotype also contributed by Mck1 and Rim15.This work was funded by a scholarship from Lucy Cavendish College (ZQ) and a scholarship awarded by National University of Defense Technology of China (LC). This work was also supported by the UNICELLSYS Collaborative Project (No. 201142) of the European Commission awarded to SGO.This is the published version. It first appeared at http://dx.doi.org/10.1371/journal.pgen.100528

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Guidance Value of Marine Functional Zoning System to Allocation of China’s Marine Resources

The issue of marine resources is receiving closer and closer attention of national marine management authorities. For this issue, it is necessary to seek basic basis from legal institutions of marine functional zoning system. This paper analyzed basic connotation, development process and basic characteristics of marine functional zoning system, discussed internal relation between marine functional zoning system and marine resource allocation, and studied guidance value of marine functional zoning system to allocation of marine resources

The Heterogeneous Effects of Multilevel Location on Farmland Abandonment: A Village-Level Case Study in Tai&rsquo;an City, China

As a global phenomenon, farmland abandonment continues to challenge the sustainability of the agri-food supply and rural development. Investigating the heterogeneous effects of multilevel location on farmland abandonment is of great importance to understand the spatial disparity and the mechanism of farmland abandonment, which has significant policy implications for food security and rural revitalization. Taking Tai&rsquo;an City as a case, this study aims to explore the impact of multilevel location on farmland abandonment at the village level and its spatial heterogeneity. The results show that (1) high accessibility to regional centers and roads, rather than remoteness, leads to a high rate of farmland abandonment; (2) the effect of location varies depending on the level of location. High-level regional centers (city centers and county centers) and roads (national and provincial highways) exert a stronger impact on farmland abandonment than low-level town centers and county highways; (3) the effect of location is topographically heterogeneous due to the influence of terrain on the marginalization of farmland. In the plains, except for county highways, the distance to different levels of regional centers and roads is significantly negatively correlated with farmland abandonment. However, in mountainous areas, only high-level regional centers have significant negative impacts

Influence of the Spatial Resolution of Remote Sensing Images on Shoreline Spatio-temporal Variations Analysis: A case of Bohai Bay, China

The traditional medium-resolution satellite images cannot meet the need of small-scale shoreline variation monitoring. In addition, researches on the influences in spatial resolution on monitoring different types of shoreline changes are rarely found and discussed. Hence, in this study, based on high resolution remote sensing images from 2010 to 2020, such as SPOT5, GF-1/6 and ZY-3 satellite images the characteristics of shoreline changes were researched by the method of digital shoreline analysis system (DSAS) and fractal dimension. Moreover, the influences on shoreline variation velocity and fractal dimension based on satellite images with different spatial resolution were analyzed corresponding Landsat images. The outputs showed that the fractal dimensions of different types of shorelines were similar based on high-and low-resolution images, yet the difference of spatial resolution had obvious influence on shoreline variation velocities of different types of shorelines. Additionally, the trend of shoreline spatio-temporal variation transitioned from drastic change to a relatively stable state. The results could provide data support for the optimization of resource utilization in the Bohai Bay area and the protection of natural resources such as coastlines and tidal flats and wetlands

Impact of Argo Observation on the Regional Ocean Reanalysis of China Coastal Waters and Adjacent Seas: A Twin-Experiment Study

A regional ocean reanalysis system of China coastal waters and adjacent seas, called CORA (China ocean reanalysis), has been recently developed at the National Marine Data and Information Service (NMDIS). In this study, based on CORA, the impact of Argo profiles on the regional reanalysis is evaluated using a twin-experiment approach. It is found that, by assimilating Argo observations, the reanalysis quality is much improved: the root mean square (RMS) error of temperature and salinity can be further reduced by about 10% and the RMS error of current can be further reduced by 18%, compared to the case only assimilating conventional in situ temperature and salinity observations. Consistent with the unique feature of Argo observations, the temperature is improved in all levels and the largest improvement of salinity happens in the deep ocean. Argo profile data have a significant impact on the regional ocean reanalysis through improvements of both hydrographic and dynamic fields

The Concept of Ocean Dumping

曹英志，国家海洋信息中心助理研究员，国际法学硕士，主要从事海洋国际立法、海洋权益维护、海域使用管理等研宄工作。 范晓婷，国家海洋信息中心副研宄员，法学学士，主要从事海洋国际立法、海洋权益维护、海域使用管理等研究工作。【中文摘要】海洋在21世纪的人类生活中越来越重要，然而人类故意向海洋倾倒废弃物，海上或沿海操作性事故和自然灾害等使得海洋环境及海洋资源受到严重污染。受各种因素的影响，人类对海洋倾废的理解不尽相同，并存在一些片面的理解，正确揭示海洋倾废概念显得尤为迫切。人类对海洋倾废概念的理解，亦经历了从萌芽、发展到成熟的历史演变，这在世界各国的海洋倾废立法当中得到了充分的体现。《联合国海洋法公约》和《1972年伦敦倾废公约》对海洋倾废概念提出了新的内涵和外延。当前，我国的海洋倾废立法面临着重大修改，研究海洋倾废概念，对我国海洋倾废管理具有重大的理论与实践意义。 【Abstract】The twenty-first century has witnessed the increasingly important role played by the oceans in human lives. Yet, wastes are being dumped into oceans deliberately, and the marine environment and resources are seriously contaminated as a result of the oceanic and coastal operational accidents, as well as the natural disasters. Due to various factors, the understanding of the concept of ocean dumping differs from each other, some of which being lopsided, making it imperious to clarify the meaning of ocean dumping. The understanding on ocean dumping has experienced a historical transition from being embryonic，developing and mature stages, as is embodied in the domestic legislations on ocean dumping worldwide. In the United Nations Convention on the Law of the Sea and 1972 London Convention on the Prevention of Marine Pollution by Dumping of Wastes and Other Matter, the concept of ocean dumping is updated both in its content and boundary. Currently，China's legislations on ocean dumping are expecting tremendous modifications and therefore, it is of great theoretical and practical value to study the concept of ocean dumping

Spatiotemporal Patterns and Morphological Characteristics of <i>Ulva prolifera</i> Distribution in the Yellow Sea, China in 2016–2018

The world&#8217;s largest macroalgal blooms, Ulva prolifera, have appeared in the Yellow Sea every summer on different scales since 2007, causing great harm to the regional marine economy. In this study, the Normalized Difference of Vegetation Index (NDVI) index was used to extract the green tide of Ulva prolifera from MODIS images in the Yellow Sea in 2016&#8315;2018, to investigate its spatiotemporal patterns and to calculate its occurrence probability. Using the standard deviational ellipse (SDE), the morphological characteristics of the green tide, including directionality and regularity, were analyzed. The results showed that the largest distribution and coverage areas occurred in 2016, with 57,384 km2 and 2906 km2, respectively and that the total affected region during three years was 163,162 km2. The green tide drifted northward and died out near Qingdao, Shandong Province, which was found to be a high-risk region. The coast of Jiangsu Province was believed to be the source of Ulva prolifera, but it was probably not the only one. The regularity of the boundary shape of the distribution showed a change that was opposite to the variation of scale. Several sharp increases were found in the parameters of the SDE in all three years. In conclusion, the overall situation of Ulva prolifera was still severe in recent years, and the sea area near Qingdao became the worst hit area of the green tide event. It was also shown that the sea surface wind played an important part in its migration and morphological changes

Current Situation and Problems of Marine Fishery in China

Marine fishery plays an essential role in promoting the employment of labor force, ensuring food safety, promoting the construction of ecological civilization and safeguarding the maritime rights and interests. The development of marine fishery is of great significance. This paper analyzed the current situation and existing problems of marine fishery in China and came up with some pertinent recommendations and measures. The area of marine fishery with authentic right is increasing year by year, and pelagic fishery constantly grows and the industrial structure is becoming more and more reasonable. However, there are still problems such as serious pollution of marine environment, frequent occurrence of marine disasters, shrinking space of fishery development, which seriously affect healthy development of the marine fishery. In this situation, it came up with recommendations including strengthening monitoring of marine fishery resources and protection of marine environment, optimizing the industrial structure, and raising the scientific and technological level of marine fisheries, to protect the sustainable development of marine fishery. It is expected to provide references for the development of marine fishery in China

On the Application of the Principle that ”No One Should Be Punished Twice for the Same Cause" in Marine Administrative Punishment

曹英志，国家海洋信息中心助理研究员，中国海洋大学国际法学硕士。 张志华，国家海洋局海域管理司海域处副处长，北京大学法学硕士。 任洁，中国海洋大学国际法学硕士。【中文摘要】“一事不再罚”原则是国际上的一项重要责任制度，它直接来源于 “一事不再理”原则。我国《行政处罚法》确立的“一事不再罚”原则有其特殊的内涵， 本文对其特殊内涵作了积极探索。本文结合国内外法学的理论研究将“一事不再 罚”原则与我国海洋行政处罚实践相结合，对“一事不再罚”原则在我国海洋行政 处罚中的适用和例外作简要探讨，并论述“一事不再罚”原则给我国海洋行政处罚 带来的启示。 【Abstract】The principle that “no one should be punished twice for the same cause” is an important legal rule internationally, which derives directly from the principle of ne bis in idem. The principle that "no one should be punished twice for the same cause", as established in the Law of the People's Republic of China on Administrative Punishments, contains special meanings, which this paper will actively explore. The authors will take theoretical studies from both domestic and foreign law circles into consideration, and, by combining the principle that "no one should be punished twice for the same cause” and the practice in China’s marine administrative punishment, briefly discuss the application of and exceptions to the principle that “no one should be punished twice for the same cause” in China’s marine administrative punishment, as well as illustrate the enlightenment that the principle brings to China's marine administrative punishment