The overexpression of GRASP might inhibit cell proliferation and invasion in hepatocellular carcinoma

This study aimed to validate the methylation of key genes in hepatocellular carcinoma (HCC) screened by bioinformatics analysis and explore whether they affected HCC cell proliferation, migration, and invasion. Using The Cancer Genome Atlas (TCGA) database, HCC-related differentially methylated positions (DMPs) were screened, genes corresponding to DMPs were selected, and prognosis-related genes were identified. A representative DMP was used to divide the DMPs into hyper- and hypomethylated groups. Expression of key genes in cell lines was detected using quantitative real-time polymerase chain reaction and western blot analysis. After treatment of HepG2 cells with 5-Aza-2′-deoxycytidine (5-Aza-DC), gene expression was observed. Bisulfite sequencing PCR assay was used to detect methylation frequency. Overexpressed GRASP lentiviral vectors were constructed to analyze their influence on cell proliferation, migration, and invasion using cell counting kit-8 and transwell assays. Forty-three HCC prognosis-related genes were screened using the TCGA database. cg00249511 (SCT) was used to divide the DMPs into hyper- and hypomethylated groups, distinguishing between high- and low-risk samples. The prognosis survival model constructed using 12 genes revealed the prognosis type. GRASP messenger RNA was downregulated in HepG2 and upregulated after 5-Aza-DC treatment. In HCC tissues, methylation frequency of GRASP was upregulated. GRASP overexpression inhibited HepG2 cell proliferation, invasion, and G-CSFR expression. Thus, GRASP might be a prognosis-related gene controlled by methylation.     

Stable isotope analysis reveals ontogenetic feeding shifts in Pacific blue marlin (Makaira nigricans) off eastern Taiwan

To gain a better understanding of the trophic ecology of Pacific blue marlin Makaira nigricans off eastern Taiwan, nitrogen and carbon stable isotopes (δ¹⁵N and δ¹³C) and Bayesian mixing models were used to explore trophic dynamics and potential ontogenetic feeding shifts across M. nigricans of different size classes. Makaira nigricans samples from east of Taiwan (n = 213) and Palau (n = 37), as well as their prey (n = 70), were collected during 2012 and 2013. Results indicated increases in δ¹⁵N with size, with values of larger size classes (> 200 cm eye-to-fork length; L_EF) significantly higher than those < 200 cm L_EF. Values of δ¹³C were negatively correlated with size. Makaira nigricans > 200 cm L_EF had the highest estimated trophic position (4.44) and also exhibited ontogenetic changes in trophic position. Large M. nigricans fed more on dolphinfish Coryphaena hippurus and hairtail Trichiurus lepturus, while smaller M. nigricans consumed smaller forage fish (e.g., moonfish Mene maculata) and cephalopods. These changes may relate to greater swimming speeds and vertical habitat use in larger M. nigricans, allowing capture and consumption of larger prey items at higher trophic positions. The high trophic level of M. nigricans east of Taiwan confirms its important role as an apex predator in marine food webs and how ecological role changes with size.     

Impacts of consumer–resource interaction transitions on persistence and long‐term interaction outcomes of random ecological networks

Despite the prevalence of context‐dependent interaction transitions in ecological systems, their impacts on persistence and interaction diversity have scarcely been explored in complex ecological networks. By using multispecies bi‐directional and unidirectional consumer–resource models, representing a continuum of interaction transitions (sign change of interaction outcomes), we investigated the effects of structural interaction transitions on persistence (the fraction of remaining species) and long‐term interaction outcomes in random ecological networks. We found that high interaction strength of exploiting resources generally decreased persistence, and high strength of providing resources increased persistence when the strength of exploiting resources was low in more complex networks; also, the networks with high persistence had a high proportion of mutualistic interactions relative to antagonistic interactions present initially and over the long term. The shifting of interaction strengths shaped the long‐term interaction compositions. Meanwhile, population dynamics, especially species extinction, affected the difference between initial and long‐term interactions. Based on classical consumer–resource theory, these results establish a transitional continuum of interaction outcomes in ecological networks and imply a theoretical association among interaction transition, community persistence and interaction diversity.     

Temperature‐dependence of minimum resource requirements alters competitive hierarchies in phytoplankton

Resource competition theory is a conceptual framework that provides mechanistic insights into competition and community assembly of species with different resource requirements. However, there has been little exploration of how resource requirements depend on other environmental factors, including temperature. Changes in resource requirements as influenced by environmental temperature would imply that climate warming can alter the outcomes of competition and community assembly. We experimentally demonstrate that environmental temperature alters the minimum light and nitrogen requirements – as well as other growth parameters – of six widespread phytoplankton species from distinct taxonomic groups. We found that species require the most nitrogen at the highest temperatures while light requirements tend to be lowest at intermediate temperatures, although there are substantial interspecific differences in the exact shape of this relationship. We also experimentally parameterize two competition models, which we use to illustrate how temperature, through its effects on species’ traits, alters competitive hierarchies in multispecies assemblages, determining community dynamics. Developing a mechanistic understanding of how temperature influences the ability to compete for limiting resources is a critical step towards improving forecasts of community dynamics under climate warming.     

The status and conservation of the Cape Gannet Morus capensis

The Cape Gannet Morus capensis is one of several seabird species endemic to the Benguela upwelling ecosystem (BUS) but whose population has recently decreased, leading to an unfavourable IUCN Red List assessment. Application of ‘JARA’ (‘Just Another Red-List Assessment,’ a Bayesian state-space tool used for IUCN Red List assessments) to updated information on the areas occupied by Cape Gannets and the nest densities of breeding birds at their six colonies, suggested that the species should be classified as Vulnerable. However, the rate of decrease of Cape Gannets in their most-recent generation exceeded that of the previous generation, primarily as a result of large decreases at Bird Island, Lambert’s Bay, and Malgas Island, off South Africa’s west coast (the western part of their range). Since the 1960s, there has been an ongoing redistribution of the species from northwest to southeast around southern Africa, and ～70% of the population now occurs on the south coast of South Africa, at Bird Island in Algoa Bay, on the eastern border of the BUS. Recruitment rather than adult survival may be limiting the present population; however, information on the seabird’s demographic parameters and mortality in fisheries is lacking for colonies in the northern part of the BUS. Presently, major threats to Cape Gannet include: substantially decreased availability of their preferred prey in the west; heavy mortalities of eggs, chicks and fledglings at and around colonies, inflicted by Cape Fur Seals Arctocephalus pusillus and other seabirds; substantial disturbance at colonies caused by Cape Fur Seals attacking adult gannets ashore; oiling; and disease.     

Exploring the antimalarial potential of the methoxy-thiazinoquinone scaffold: Identification of a new lead candidate

A small library of antiplasmodial methoxy-thiazinoquinones, rationally designed on the model of the previously identified hit 1, has been prepared by a simple and inexpensive procedure. The synthetic derivatives have been subjected to in vitro pharmacological screening, including antiplasmodial and toxicity assays. These studies afforded a new lead candidate, compound 9, endowed with higher antiplasmodial potency compared to 1, a good selectivity index when tested against a panel of mammalian cells, no toxicity against RBCs, a synergistic antiplasmodial action in combination with dihydroartemisinin, and a promising inhibitory activity on stage V gametocyte growth. Computational studies provided useful insights into the structural requirements needed for the antiplasmodial activity of thiazinoquinone compounds and on their putative mechanism of action.     

Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008–2019)

Cyclooxygenase-2 is a very important physiological enzyme playing key roles in various biological functions especially in the mechanism of pain and inflammation, among other roles, making it a molecule of high interest to the pharmaceutical community as a target. COX 2 enzyme is induced only during inflammatory processes or cancer and reflects no role in the guarding stomach lining. Thus, selective COX-2 inhibition can significantly reduce the adverse effects including GI tract damage and hepatotoxic effects of traditional NSAIDs like aspirin, ibuprofen, etc. Recent developments on COX-2 inhibitors is primarily focused on improving the selectivity index of the drug towards COX-2 along with enhancing the potency of the drug by modifying the scaffolds of Coxibs currently in the market like Celecoxib, Indomethacin, Oxaprozin, etc. We have reported the progress on new COX-2 inhibitors in the last decade (2008–2019) focussing on five heterocyclic rings- Pyrazole, Indole, Oxazole, Pyridine and Pyrrole. The addition of various moieties to these core rings and their structure-activity relationship along with their molecular modelling data have been explored in the article. This review aims to aid medicinal chemists in the design and discovery of better COX-2 inhibitors constructed on these five heterocyclic pharmacophores.     

Main stem and off‐channel habitat use by juvenile Chinook salmon in a sub‐Arctic riverscape

相似文献   

Computational models evaluating the impact of sieve plates and radial water exchange on phloem pressure gradients

The sugar conducting phloem in angiosperms is a high resistance pathway made up of sieve elements bounded by sieve plates. The high resistance generated by sieve plates may be a trade‐off for promoting quick sealing in the event of injury. However, previous modeling efforts have demonstrated a wide variation in the contribution of sieve plates towards total sieve tube resistance. In the current study, we generated high resolution scanning electron microscope images of sieve plates from balsam poplar and integrated them into a mathematical model using Comsol Multiphysics software. We found that sieve plates contribute upwards of 85% towards total sieve tube resistance. Utilizing the Navier–Stokes equations, we found that oblong pores may create over 50% more resistance in comparison with round pores of the same area. Although radial water flows in phloem sieve tubes have been previously considered, their impact on alleviating pressure gradients has not been fully studied. Our novel simulations find that radial water flow can reduce pressure requirements by half in comparison with modeled sieve tubes with no radial permeability. We discuss the implication that sieve tubes may alleviate pressure requirements to overcome high resistances by regulating their membrane permeability along the entire transport pathway.