Unimodal relationship between three-dimensional soil heterogeneity and plant species diversity in experimental mesocosms

Abstract

Aims

Soil heterogeneity is a primary mechanism explaining plant species diversity. Yet, controlled experiments yield inconsistent soil heterogeneity-diversity (SHD) relationships, ranging from positive, neutral to negative.

Methods

Here we investigated the SHD relationship by experimentally alternating nutrient-rich and nutrient-poor substrate in three dimensions, creating four levels of soil configurational heterogeneity (cell sizes 0, 12, 24 and 48 cm). Across each mesocosm, a mixture of species with high and low nitrogen requirements was evenly sown.

Results

Contrary to earlier experimental findings, this approach yielded a unimodal SHD relationship, peaking at cell size 12 cm. This pattern originated mainly from increased plant diversity of species with high nitrogen requirement. Diversity increases with configurational heterogeneity were not due to greater variation in light niches, and diversity decreases were not due to success of fast growing species. Strikingly, plant density increased monotonically with increasing configurational heterogeneity, indicating that not only more species but also more individuals could coexist.

Conclusions

This study provides experimental evidence for unimodal SHD curves in plant communities, which has hitherto only been predicted by models. Our results carry a striking similarity with other unimodal response patterns of plant species diversity, notably in diversity–disturbance and diversity–productivity relationships.

from Energy Ecology Environment Ambio via Terpsi Hori on Inoreader http://bit.ly/2Ft7itm

Levels, distributions, and ecological risk assessments of polybrominated diphenyl ethers and alternative flame retardants in river sediments from Vaal River, South Africa

Abstract

Sediments are known to be the ultimate sink for most pollutants in the aquatic environment. In this study, the concentrations of both legacy polybrominated diphenyl ethers (PBDEs) and alternative halogenated flame retardants (AHFRs) were measured in sediments samples from the Vaal River catchment. The concentrations of Σ₇BDE-congeners ranged from 20 to 78 ng g⁻¹ dry weight (dw) with BDE-209, -99, and -153 as the dominant congeners. The concentrations observed ranged from 9.4–56, 4–32, and 1–10.6 ng g⁻¹ for BDE-209, -99, and -153, respectively. The concentrations of AHFRs, mainly contributed by decabromodiphenyl ethane (DBDPE) at approximately 95% of total AHFRs, ranged from 64 to 359 ng g⁻¹ dw while the concentration of polybrominated biphenyls (PBBs), mainly PBB-209, ranged from 3.3–7.1 ng g⁻¹ dw. The ratios of AHFRs to PBDEs observed in this study were 0.76, 1.17, and 7.3 for 2-ethyl-1-hexyl-2,3,4,5-tetrabromobenzoate and bis-(2-ethylhexyl)-tetrabromophthalate (EH-TBB & BEH-TEBP)/penta-BDE; 1,2-bis-(2,4,6-tribromophenoxy) ethane (BTBPE)/octa-BDE; and DBDPE/BDE209, respectively. These results indicate dominance of some AHFRs compared to PBDEs. Our results indicates that BDE-99 poses high risk (RQ > 1) while BDE-209 posed medium risk (0.1 < RQ < 1). Though the concentration of DBDPE was several orders of magnitude higher than BDE209, its ecological risk was found to be negligible (RQ < 0.01). Thus, more attention is required to regulate the input (especially the e-waste recycling sites) of brominated flame retardants into the environment.

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Activation of c-Met in cancer cells mediates growth-promoting signals against oxidative stress through Nrf2-HO-1

Activation of c-Met in cancer cells mediates growth-promoting signals against oxidative stress through Nrf2-HO-1

Activation of c-Met in cancer cells mediates growth-promoting signals against oxidative stress through Nrf2-HO-1, Published online: 15 January 2019; doi:10.1038/s41389-018-0116-9

Activation of c-Met in cancer cells mediates growth-promoting signals against oxidative stress through Nrf2-HO-1

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[ASAP] 11-Step Total Synthesis of Teleocidins B-1–B-4

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b13697

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Measures to improve wine malolactic fermentation

Abstract

This review focuses on the considerable amount of research that has been directed towards the improvement of efficiency and reliability of malolactic fermentation (MLF), which is important in winemaking. From this large body of work, it is clear that reliable MLF is essential for process efficiency and prevention of spoilage in the final product. Impediments to successful MLF in wine, the impact of grape and wine ecology and how this may affect MLF outcome are discussed. Further focus is given to how MLF success may be enhanced, via alternative inoculation strategies, MLF progress sensing technologies and the use of different bacterial species. An update of how this information may be used to enhance and improve sensory outcomes through metabolite production during MLF and suggestions for future research priorities for the field are also provided.

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Research on the electrostatic characteristic of coal-fired fly ash

Abstract

China is the biggest consumer of coal. Every year, half or more of China's coal is used in the power industry. Most thermal power plants in China use electrostatic precipitators to treat solid particulate matter in flue gas. The efficiency of the electrostatic precipitator in removing dust has a considerable influence on atmospheric pollutants. However, the most important factor affecting the efficiency of the electrostatic precipitator in removing dust is the dielectric properties of the fly ash. Through the study of volt-ampere characteristics, electrical and capacitive properties, and electrical breakdown characteristics of coal-fired fly ash, it is found that the V–I characteristics of ash samples in thermal power plant do not strictly follow the formula ( \( R=\frac{U}{I} \) ), the type of coal, and the chemistry of coal. Ingredients are related; disparate types of ash samples have disparate capacitances, and the measurement of capacitive contrast resistance has a certain influence.

from Energy Ecology Environment Ambio via Terpsi Hori on Inoreader http://bit.ly/2Dc5zWR

Impact of substrate material on algal biofilm biomass growth

Abstract

Algae are being grown for wastewater purification and biofuels production. Their growth on a substrate facilitates these uses by allowing facile separation of algae from the water. Here, we compare different materials to determine which would best serve this purpose. A mixed culture of Anabaena and Chlorella was grown on various synthetic and natural fiber fabric substrates in a trough system with recirculating simulated wastewater. Filter materials studied as substrates for algal growth were muslin, olefin, pellon (acrylic), two types of polyester, and two types of nylon. Biomass accumulation on the various filter substrates was recorded at 7, 14, and 28 days. Filters were weighed before and after the growth periods and changes in dry biomass were recorded. Biomass accumulation was significantly affected by the fabric type. Olefin fostered the greatest increase in biomass while nylon and polyester also supported competitive increases in biomass. Pellon showed the smallest biomass increase and muslin decreased in mass due to material disintegration. Other concerns such as abrasion resistance and UV susceptibility are discussed.

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Isolation, characterization, and therapeutic activity of bergenin from marlberry ( Ardisia colorata Roxb.) leaf on diabetic testicular complications in Wistar albino rats

Abstract

Bergenin is one of the phytochemical constituents in marlberry (Ardisia colorata Roxb.) having antioxidant, anti-diabetic, and anti-inflammatory properties. A. colorata has been used as an herbal medicine in Southeast Asia particularly in Northeast India to treat diabetes. Bergenin was isolated from methanol extract of A. colorata leaf (MEACL) by column chromatography and TLC profiling. Characterization and structural validation of bergenin were performed by spectroscopic analyses. A LC-ESI-MS/MS method was developed for the quantitation of bergenin and validated as per the guidelines of FDA and EMA. The validated method was successfully utilized to quantify bergenin concentration in MEACL samples. Therapeutic efficacy of bergenin was investigated on streptozotocin-induced diabetic rats by following standard protocols. Bergenin supplementation significantly improved the physiological and metabolic processes and in turn reverses diabetic testicular dysfunction via increasing serum testosterone concentrations and expression pattern of PCNA, improving histopathological and histomorphometric manifestations, modulating spermatogenic events and germ cell proliferation, restoring sperm quality, reducing sperm DNA damage, and balancing the antioxidant enzymes levels. Hence, A. colorata leaf is one of the alternate rich resources of bergenin and could be used as a therapeutic agent for diabetic testicular complications.

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An evaluation of the levels of organochlorine compounds (OCPs and PCBs) in cultured freshwater and wild sea fish eggs as an exposure biomarker for environmental contamination

Abstract

In this study, the eggs of 30 wild Black Sea whiting (Merlangius merlangus euxinus, Nordmann, 1840) and 30 farmed freshwater rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) collected from Samsun Province in Turkey were analyzed to determine the level of contamination by nine organochlorine pesticides (OCPs), namely α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH (lindane), hexachlorobenzene (HCB), aldrin, 2,4′-dichlorodiphenyltrichloroethane (DDT), 4,4′-DDT, 2,4′-dichlorodiphenyldichloroethylene (DDE), 4,4′-DDE, and 15 polychlorinated biphenyls (PCBs) (PCB-28, -70, -74, -81, -99, -101, -118, -138, -153, -156, -170, -180, -183, -187, and -208), and their potential use as biomarkers to monitor levels of environmental contamination. OCPs and PCBs in the fat of fish eggs were extracted cryogenically and their concentrations were determined with a gas chromatography-electron capture detector (GC-ECD). The whiting eggs showed high OCP and PCB levels compared to the rainbow trout eggs. The median ∑ DDT values for whiting and rainbow trout eggs were 1601.62 ng g⁻¹ fat (range 824.87–5049.81) and 406.49 ng g⁻¹ fat (range 199.88–588.82); median ∑Indicator PCBs were 1264.24 ng g⁻¹ fat (range 520.05–6140.32) and 82.11 ng g⁻¹ fat (range 2.85–215.97); and median ∑ HCHs were 155.66 ng g⁻¹ fat (range 35.45–330.40) and 13.48 ng g⁻¹ fat (range 4.44–66.44), respectively. In the whiting eggs, the ∑Indicator PCB level was above the maximum residue limit (MRL) of 200 ng g⁻¹ fat stated in the European Commission Regulation (EC) and Turkish Food Codex (TFC). In addition, there was a significant difference between the contamination levels of the eggs of the two species. In conclusion, it appears that fish eggs can serve as a valuable biomarker for the level of contamination of persistent organochlorine contaminants in different aquatic environments.

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Enrichment of cordycepin for cosmeceutical applications: culture systems and strategies

Abstract

Cordyceps spp. is the herbal medication initially used in China and has been reported as the unique resource of cordycepin. Cordycepin exhibits many health benefits, including anti-photoaging and anti-pigmentation; therefore, it potentially is a bioactive ingredient of cosmetic products. In order to enrich cordycepin content in Cordyceps, two artificial cultivation procedures, which are solid-state fermentation and liquid culture, were developed and optimized. The aim of this review is to illustrate cordycepin biosynthesis pathway in Cordyceps, and its bioactivity for cosmeceutical applications, as well as comparing the two different cultivation procedures. The basic model of artificial cultivation of Cordyceps is introduced; meanwhile, the potential application of modern biotechnology to the artificial cultivation is also discussed. This review should be of interest to the readers for the development of cordycepin bioproduction in order to be applied in cosmeceutical industry and some other uses.

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Plant sprouts on the Moon for first time ever

Plant sprouts on the Moon for first time ever

Plant sprouts on the Moon for first time ever, Published online: 15 January 2019; doi:10.1038/d41586-019-00159-0

China's Chang'e-4 lander has sent back pictures of a cotton seed sprouting in a miniature biosphere experiment on the craft.

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Next-generation LHC: CERN lays out plans for €21-billion super-collider

Next-generation LHC: CERN lays out plans for €21-billion super-collider

Next-generation LHC: CERN lays out plans for €21-billion super-collider, Published online: 15 January 2019; doi:10.1038/d41586-019-00173-2

The proposed facility would become the most powerful collider ever built.

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Daily briefing: What 100,000 twins can tell us about nature versus nurture

Daily briefing: What 100,000 twins can tell us about nature versus nurture

Daily briefing: What 100,000 twins can tell us about nature versus nurture, Published online: 15 January 2019; doi:10.1038/d41586-019-00170-5

Genes account for about 40% of variations in early adult health, immune therapy hits mutated cancers harder and why South Africa must stop paying academics by the paper.

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[ASAP] Statistical Analysis of Nonuniform Volume Distributions for Droplet-Based Digital PCR Assays

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b09073

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[ASAP] Generalized Preparation of Two-Dimensional Quasi-nanosheets via Self-assembly of Nanoparticles

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b12415

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[ASAP] Biophysical Characterization of a Disabled Double Mutant of Soybean Lipoxygenase: The “Undoing” of Precise Substrate Positioning Relative to Metal Cofactor and an Identified Dynamical Network

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b10992

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[ASAP] A Hendecad Motif Is Preferred for Heterochiral Coiled-Coil Formation

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b11246

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[ASAP] Catalysts Confined in Programmed Framework Pores Enable New Transformations and Tune Reaction Efficiency and Selectivity

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b11221

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[ASAP] A Redox Strategy for Light-Driven, Out-of-Equilibrium Isomerizations and Application to Catalytic C–C Bond Cleavage Reactions

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b12552

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Essential oil of Chrysanthemum indicum L.: potential biocontrol agent against plant pathogen Phytophthora nicotianae

Abstract

Phytophthora nicotianae is currently considered one of the most devastating oomycete plant pathogens, and its control frequently relies solely on the use of systemic fungicides. There is an urgent need to find environment-friendly control techniques. This study examined the chemical composition, inhibitory activity, and possible modes of action of the essential oil of Chrysanthemum indicum L. (EOC) flower heads against P. nicotianae. The EOC was obtained using hydrodistillation at a 0.15% yielded. It inhibited mycelial growth and spore germination of P. nicotianae at a minimum inhibitory concentration (MIC) of 200 μL/L, and exhibited fumigation effects (92.68% inhibition at 157.48 μL/L). Marked deformation of P. nicotianae mycelia included deformed tip enlargement, shrinkage, and rupture. Further, 55 and 47 compounds were identified using gas chromatography-mass spectrometry (GC-MS) and headspace solid-phase microextraction (HS-SPME) GC-MS analyses, representing 88.2% and 98.91% of the total EOC, respectively. Monoterpenes (25.77%) and sesquiterpenes (54.14%) were the major components identified using GC-MS, whereas monoterpenes were the main constituents in the HS-SPME GC-MS analysis. The higher proportions of sesquiterpenes and monoterpenes could be responsible for the inhibitory activity of EOC, which increased mycelia membrane permeability and the content of mycelial malondialdehyde (MDA) in a dose-dependent manner. Cell death also occurred. Thus, destruction of the cell wall and membrane might be two modes of action of EOC. Our results would be useful for the development of a new plant source of fungicide for P. nicotianae-induced disease.

from Energy Ecology Environment Ambio via Terpsi Hori on Inoreader http://bit.ly/2RrERSQ

Seasonal Dynamics of Benthic Foraminiferal Biocoenosis in the Tropical Saquarema Lagoonal System (Brazil)

Abstract

This study investigates and compares the seasonal variations during winter and summer of living benthic foraminiferal assemblages in the Saquarema Lagoon System (SLS) located in a tropical coastal region of SE Brazil. The physicochemical parameters in the SLS presented strong differences between both seasons; however, they remained quite homogeneous in winter and exhibited great oscillations in summer. In the study area, 29 and 19 living foraminiferal species were identified in summer and winter, respectively. Ammonia tepida was the dominant species in both seasons followed by Ammonia parkinsoniana and Cribroelphidium excavatum. The detrended correspondence analysis showed that in the SLS: the calcareous species, such as Adelosina carinatastriata, Bulimina patagonica, and Miliolinella antartica were mostly influenced by high dissolved oxygen contents and low temperature, whereas the agglutinated foraminiferal species were indicators of the most confined lagoonal areas, under the lowest pH and salinity values. The results of this work evidence that the seasonal variation in the SLS might play a more important role in the benthic foraminiferal assemblages' distribution than the anthropogenic impacts and shows the importance of seasonal studies for coastal biomonitoring programs.

from Energy Ecology Environment Ambio via Terpsi Hori on Inoreader http://bit.ly/2RNEJws

Next-generation LHC: CERN lays out plans for €21-billion super-collider

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Spatiotemporal differences in the arbuscular mycorrhizal fungi communities in soil and roots in response to long-term organic compost inputs in an intensive agricultural cropping system on the North China Plain

Abstract

Purpose

Fertilizer management is important for minimizing nutrient losses from intensive agroecosystems. An increasing amount of organic fertilizer has been applied to overcome the problems associated with mineral fertilizers. Thus, an understanding of the diversity and community structure changes in arbuscular mycorrhizal fungi (AMF) in response to long-term organic fertilizer management can be potentially significant in the development of nutrient management strategies.

Materials and methods

Here, a study was conducted to investigate the vertical distribution of AMF in a calcareous field and the temporal structure of AMF in maize roots with different levels of continuous fertilization over a 13-year period. T-RFLP and clone library construction were used to investigate AMF community in this study. Canonical correspondence analysis was performed to determine the significance of environmental variable that may affect the AMF community composition.

Results and discussion

Our results showed that the Shannon-Weiner and evenness indexes of soil AMF community decreased, while AMF richness was not significantly affected. Organic compost application reduced root colonization, while the negative influence of conventional inorganic fertilization was minor. The effect was significant at 13 leaf collar stage of maize. Crop phenology especially growth stages might override fertilizer supply in determining the community composition of active root inhabiting AM fungi. Significant differences in the community structure of soil AMF were observed between control and organic compost treatments in surface soil, and the community shift was primarily attributable to soil organic matter and nutrient contents (total nitrogen and carbon, Olsen-P, and exchangeable K). Vertical distribution of AMF was significantly related to soil electrical conductivity and pH values.

Conclusions

Our results indicated that AMF community assemblage was complex and dependent on fertilization-mediated changes in soil properties, soil depth, and crop phenology. The modification of AMF communities by fertilization may have great impact on soil health and ecosystem services in intensive agroecosystems.

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Use of cognitive enhancers: methylphenidate and analogs

OBJECTIVE: In the last decades, several cognitive-enhancing drugs have been sold onto the drug market. Methylphenidate and analogs represent a sub-class of these new psychoactive substances (NPS). We aimed to review the use and misuse of methylphenidate and analogs, and the risk associated. Moreover, we exhaustively reviewed the scientific data on the most recent methylphenidate analogs (methylphenidate and ethylphenidate excluded).

MATERIALS AND METHODS: Literature search was performed on methylphenidate and analogs, using specialized search engines accessing scientific databases. Additional reports were retrieved from international agencies, institutional websites, and drug user forums.

RESULTS: Methylphenidate/Ritalin has been used for decades to treat attention deficit disorders and narcolepsy. More recently, it has been used as a cognitive enhancer and a recreational drug. Acute intoxications and fatalities involving methylphenidate were reported. Methylphenidate was scheduled as an illegal drug in many countries, but NPS circumventing the ban and mimicking the psychostimulant effects of methylphenidate started being available: ethylphenidate, 3,4-dichloromethylphenidate, 3,4-dichloroethylphenidate, 4-fluoromethylphenidate, 4-fluoroethylphenidate, methylnaphthidate, ethylnaphthidate, isopropylphenidate, propylphenidate, 4-methylmethylphenidate, and N-benzylethylphenidate have been available in the past few years. Only little data is currently available for these substances. Many intoxications involving methylphenidate analogs were reported. To date, ethylphenidate was involved in 28 fatalities, although it was reportedly directly related to the cause of death in only 7 cases; 3,4-dichloroethylphenidate was involved in 1 death.

CONCLUSIONS: The rapid expansion of methylphenidate analogs onto the drug market in the past few years makes likely the occurrence of intoxications and fatalities in the next years. Careful monitoring and systematic control of methylphenidate analogs should be undertaken to reduce the uprising threat, and education efforts should be made among high-risk populations.

L'articolo Use of cognitive enhancers: methylphenidate and analogs sembra essere il primo su European Review.

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Plant sprouts on the Moon for first time ever

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Activation of c-Met in cancer cells mediates growth-promoting signals against oxidative stress through Nrf2-HO-1

from A via a.sfakia on Inoreader https://go.nature.com/2Rr59EZ

Spatially Explicit Estimates of In Situ Filtration by Native Oysters to Augment Ecosystem Services during Restoration

Abstract

US west coast populations of the native Olympia oyster Ostrea lurida declined precipitously in the late nineteenth and early twentieth centuries and were often replaced by the non-native Pacific oyster (Crassostrea gigas) by the aquaculture industry. Recovery of native oyster ecosystem services derived from their suspension feeding activities (termed "filtration services" (FS)) often serves as a powerful incentive for restoration of populations of O. lurida along the US west coast despite uncertainty about the potential effects of their filtration activities on concentrations of suspended particulate matter. Here, we provide an improved FS model for O. lurida and C. gigas in Yaquina Bay, OR, that is based on both in situ feeding behavior and the complex hydrodynamics of the estuary. The total area and the order of locations chosen for oyster restoration in Yaquina Bay were examined to determine how oyster FS could be maximized with limited resources. These modeling efforts quantified estimates showing (1) native oysters, if restored in Yaquina Bay to historic levels, may contribute nearly an order of magnitude greater FS than previously estimated; (2) C. gigas contributes significantly greater FS than O. lurida, especially during the wet season; (3) FS provided by either species is highly dependent upon seasonal river forcing and salinity; (4) spatial variation in FS arises from the hydrodynamics of the system, uneven oysters distributions, and upstream pre-filtering. We found that spatially explicit models demonstrated the benefits of prioritizing restoration to areas with the greatest FS potential, rather than placing oysters randomly within historic habitats. Directing restoration in this manner used between 75% (dry season) and 60% (wet season) less of the restored area needed to achieve comparable FS with randomly placed oysters.

from Energy Ecology Environment Ambio via Terpsi Hori on Inoreader http://bit.ly/2Fu5zDV

Particle Processing by Olympia Oysters Ostrea lurida and Pacific Oysters Crassostrea gigas

Abstract

The native Olympia oyster (Ostrea lurida) has been the subject of few detailed feeding studies compared with many other species of bivalve mollusk. More information on this species' feeding activity and behavior are needed to better understand its historical ecological role in Pacific Northwest (PNW) estuaries, compared with that of the widely farmed, well-studied, non-native Pacific oyster (Crassostrea gigas). In this study, the feeding physiology and particle processing behaviors of O. lurida and C. gigas were examined in both controlled laboratory experiments and in situ trials that spanned the wet and dry seasons of the PNW. It was hypothesized that O. lurida would have lower filtration and particle processing rates than those of C. gigas. Results supported this hypothesis in that filtration and absorption rates of the Pacific oyster were significantly greater than those of O. lurida under laboratory conditions. In the field, C. gigas was also found to filter, absorb, and deposit organic material at significantly greater rates than O. lurida. These observations explain the previously reported greater growth rates of C. gigas relative to those of O. lurida. Furthermore, after applying data collected here to recent modeling efforts, it estimated that C. gigas could potentially remove between 1.2 and 3.6-fold and deposit between 1.6- and 4.6-fold more organic suspended material than comparable, historic populations of O. lurida in the PNW.

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[ASAP] Sydnone-Based Approach to Heterohelicenes through 1,3-Dipolar-Cycloadditions

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b11465

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[ASAP] Rapid Faraday Rotation on e-Iron Oxide Magnetic Nanoparticles by Visible and Terahertz Pulsed Light

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b12910

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[ASAP] Spotlights on Recent Publications

Journal of the American Chemical Society

DOI: 10.1021/jacs.9b00435

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Daily briefing: What 100,000 twins can tell us about nature versus nurture

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Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis

Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis

Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis, Published online: 15 January 2019; doi:10.1038/s41385-019-0132-x

Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis

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Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis

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Effect of spiral undersampling patterns on FISP MRF parameter maps

Publication date: Available online 15 January 2019

Source: Magnetic Resonance Imaging

Author(s): Gregor Körzdörfer, Josef Pfeuffer, Thomas Kluge, Matthias Gebhardt, Bernhard Hensel, Craig H. Meyer, Mathias Nittka

Abstract

Purpose

Artifacts arising from undersampling are not always treatable as incoherent noise for the pattern matching process in Magnetic Resonance Fingerprinting (MRF). To estimate the effect of undersampling artifacts on MRF quantitative results, spiral sampling trajectories and their temporal variation is examined.

Methods

The effect of sampling trajectories and their variation during the MRF experiment was assessed by characterizing aliasing artifacts. Temporal rearrangements of sampling trajectories were tested and evaluated in simulations and scans of phantoms and in a volunteer brain.

Results

Results show that some temporal variations of sampling patterns can lead to spatial biases in MRF parameter maps. Observed effects are consistent with derived performance indicators for different interleaving schemes, leading to substantially improved MRF sampling patterns.

Conclusion

With the help of the presented simulation framework, MRF implementations can be investigated and improved. This was demonstrated for a spiral FISP (Fast imaging with steady-state free precession) MRF implementation, where a significantly improved interleaving scheme was identified, and confirmed by experiment.

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Susceptibility weighted MRI after uterine artery embolization for leiomyoma

Publication date: Available online 15 January 2019

Source: Magnetic Resonance Imaging

Author(s): Yasuyuki Yamahana, Tetsuya Katsumori, Hiroshi Miura, Shunsuke Asai, Sachimi Yamada, Akiko Takahata, Kei Yamada

Abstract

Purpose

To evaluate whether susceptibility-weighted MR imaging (SWI) findings are associated with tumor infarction on contrast-enhanced MRI (CE-MRI) after uterine artery embolization (UAE) for leiomyoma.

Methods

This was a single institution, retrospective study. Between February 2016 and April 2017, 27 consecutive patients underwent UAE and completed SWI and CE-MRI before and 1 week after UAE. Two blinded readers independently reviewed the MRI of 261 tumors ≥1 cm in all patients. We evaluated the relationship between the hypointense peripheral rim observed on the tumor surface on post-procedural SWI and the infarction rates (≥90%, <90%) of each tumor based on post-procedural CE-MRI. Inter-reader correlation coefficients (ICC) and the sensitivity and specificity of the rim were measured.

Results

Substantial inter-reader agreement was noted in post-procedural SWI interpretations (ICC = 0.681, 95% CI; 0.547, 0.771). The rim was observed in 66.7% (174/261) of tumors by reader 1 and 55.9% (146/261) of tumors by reader 2 on post-procedural SWI. Correlations were observed between the rim and ≥90% tumor infarction by readers 1 and 2 (Spearman's coefficient = 0.474 and 0.438, p < 0.001 and p < 0.001, respectively). The sensitivity and specificity of the rim to tumor infarction were 77.2 and 82.6% (reader 1), and 65.8 and 100% (reader 2), respectively.

Conclusions

The present study demonstrated that the hypointense peripheral rim was observed on some leiomyomas on SWI immediately after UAE. The rim correlated with tumor infarction on post-procedural CE-MRI. This SWI finding was helpful for evaluating embolic effects on leiomyomas in the acute phase after UAE.

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Space-time variant weighted regularization in compressed sensing cardiac cine MRI

Publication date: Available online 14 January 2019

Source: Magnetic Resonance Imaging

Author(s): Alejandro Godino-Moya, Javier Royuela-del-Val, Muhammad Usman, Rosa-María Menchón-Lara, Marcos Martín-Fernández, Claudia Prieto, Carlos Alberola-López

Abstract

Purpose

To analyze the impact on image quality and motion fidelity of a motion-weighted space-time variant regularization term in compressed sensing cardiac cine MRI.

Methods

k-t SPARSE-SENSE with temporal total variation (tTV) is used as the base reconstruction algorithm. Motion in the dynamic image is estimated by means of a robust registration technique for non-rigid motion. The resulting deformation fields are used to leverage the regularization term. The results are compared with standard k-t SPARSE-SENSE with tTV regularization as well as with an improved version of this algorithm that makes use of tTV and temporal Fast Fourier Transform regularization in x-f domain.

Results

The proposed method with space-time variant regularization provides higher motion fidelity and image quality than the two previously reported methods. Difference images between undersampled reconstruction and fully sampled reference images show less systematic errors with the proposed approach.

Conclusions

Usage of a space-time variant regularization offers reconstructions with better image quality than the state of the art approaches used for comparison.

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Payouts push professors towards predatory journals

Payouts push professors towards predatory journals

Payouts push professors towards predatory journals, Published online: 15 January 2019; doi:10.1038/d41586-019-00120-1

If South Africa truly wants to encourage good research, it must stop paying academics by the paper, says David William Hedding.

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Stroke drug shows promise for Alzheimer’s disease

Stroke drug shows promise for Alzheimer's disease

Stroke drug shows promise for Alzheimer's disease, Published online: 15 January 2019; doi:10.1038/d41586-019-00147-4

Genetically engineered protein prevents brain damage that leads to memory loss.

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From the archive

From the archive

From the archive, Published online: 15 January 2019; doi:10.1038/d41586-019-00127-8

How Nature reported the death of Theodore Roosevelt in 1919, and a collection of inventions in 1969.

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3D printing gets a lift from light

3D printing gets a lift from light

3D printing gets a lift from light, Published online: 15 January 2019; doi:10.1038/d41586-019-00102-3

A sophisticated technique can make complex objects in a single shot by blasting resin with two wavelengths of light.

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How much can forests fight climate change?

How much can forests fight climate change?

How much can forests fight climate change?, Published online: 15 January 2019; doi:10.1038/d41586-019-00122-z

Trees are supposed to slow global warming, but growing evidence suggests they might not always be climate saviours.

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Author Correction: Widespread but heterogeneous responses of Andean forests to climate change

Author Correction: Widespread but heterogeneous responses of Andean forests to climate change

Author Correction: Widespread but heterogeneous responses of Andean forests to climate change, Published online: 15 January 2019; doi:10.1038/s41586-018-0862-z

Author Correction: Widespread but heterogeneous responses of Andean forests to climate change

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Mass fish deaths in Australia set to continue

Mass fish deaths in Australia set to continue

Mass fish deaths in Australia set to continue, Published online: 15 January 2019; doi:10.1038/d41586-019-00146-5

Drought conditions and poor water management have contributed to the events.

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Saving snow leopards in a war zone

Saving snow leopards in a war zone

Saving snow leopards in a war zone, Published online: 15 January 2019; doi:10.1038/d41586-019-00125-w

Conflict and conservation became unlikely bedfellows in Afghanistan, finds Thomas McCarthy.

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How to make your podcast stand out in a crowded market

How to make your podcast stand out in a crowded market

How to make your podcast stand out in a crowded market, Published online: 15 January 2019; doi:10.1038/d41586-019-00128-7

Researchers are creating their own podcasts on topics ranging from exoplanets to graduate-student finances.

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Stroke drug shows promise for Alzheimer’s disease

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Water-soluble ion components of PM 10 during the winter-spring season in a typical polluted city in Northeast China

Abstract

From January 1 to April 22, 2014, an online analyzer for monitoring aerosols and gases (MARGA) was used to measure and analyze water-soluble ions in inhalable particulate matter with a diameter less than 10 μm (PM₁₀) during winter-spring in Shenyang city, China. The results yielded three main findings. (1) During the entire observation period and in seven pollution episodes, SO₄²⁻, NO₃⁻, and NH₄⁺ (SNA) accounted for 84.4–93.1% of the total water-soluble ions (TWSIs). TWSIs accounted for 32% of PM₁₀ mass during the entire observation period, and the contribution of TWSIs in PM₁₀ ranged from 33.4–43.1% in the seven pollution episodes. The contribution of TWSIs components increased during the pollution episodes, but certain differences were observed in different pollution episodes. In terms of ionic equilibrium, the total concentration of negative ions was slightly greater than that of positive ions and the difference was 3.1% of the total ion load on average, indicating that local aerosols are mainly neutral. The water-soluble ions show clear diurnal variation with the high concentration around 09:00 for SO₄²⁻, NH₄⁺, and Cl⁻ which is consistent with the high heating grade index. (2) Pollution episodes often occur in Northeast China, especially during the winter period. Due to the low temperature in the winter, the local coal burning for heating is one of the main sources of pollution besides vehicle exhaust and industrial pollution, which is supported by the higher NO₃⁻/SO₄²⁻ ratio in April than that in January to March. Sometimes, under the prevailing wind directions of W and SSW, the long-distance transport of pollutants from the Beijing-Tianjin-Hebei region and Shandong province superimposed on local pollution leads to the most severe pollution, such as Ep3 and Ep5. (3) SO₄²⁻ concentration is closely related to ambient water vapor pressure (e*), with increase as e* increased depending on the temperature. NO₃⁻ concentration showed a linear relationship of excess NH₄⁺, which suggests homogeneous gas-phase reaction of ammonia and nitric acid is possibly an important pathways of nitrate formation in the haze pollution process in Shenyang City. In addition, our results also suggest the nighttime liquid-phase reaction may cause large increases of nitrate in the haze pollution process.

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Experimental assessment and multi-response optimization of diesel engine performance and emission characteristics fuelled with Aegle marmelos seed cake pyrolysis oil-diesel blends using Grey relational analysis coupled principal component analysis

Abstract

This research focuses on the detailed experimental assessment of compression ignition (CI) engine behavior fuelled with Aegle marmelos (AM) seed cake pyrolysis oil blends. The study on effects of engine performance and emission a characteristic was designed using L₂₅ orthogonal array (OA). These multi-objectives were normalized through gray relational analysis (GRA). Likewise, the principal component analysis (PCA) was performed to assess the weighting values respective to every performance and emission characteristics. The variability induced by using the input process parameters was allocated using analysis of variance (ANOVA). Hence, GRA-coupled PCA were employed to determine the optimal combination of CI engine control factors. The greater combination of engine characteristics levels were selected with F₅ and W₅. The higher brake thermal efficiency (BTE) have been obtained for F20 fuel as 22.01% at peak engine load, which is 11.43% for diesel. At peak load condition, F20 fuel emits 14.99% lower HC and 18.52% lower CO as compared to diesel fuel. The improved engine performance and emission characters can be attained by setting the optimal engine parameter combination as F20 blend at full engine load condition. The validation experiments show an improved average engine performance of 67.36% and average lower emission of 64.99% with the composite desirability of 0.8458.

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Analysis of the spatial variation of indoor radon concentrations (national survey in Bulgaria)

Abstract

This paper presents the methodology and results of the national radon survey in Bulgaria and its spatial variability. The measurements were carried out in 2778 dwellings using CR-39 track detectors over two successive 9 and 3-month periods from April 2015 to March 2016. The arithmetic (AM) and geometric (GM) means of annual indoor radon concentration were 111 ± 105 Bq/m³ and 81 Bq/m³ (GSD = 2.15), respectively. The distribution of data has been accepted to be log-normal. Two hypotheses have been investigated in the paper. The first one was a spatial variation of indoor radon concentration and the second was spatiality of the factor that influences radon variation. The indoor radon concentrations in the 28 districts have been significantly different, which prove the first hypothesis. The influence of the factors, geology (geotectonic unit, type of rock, and faults distance of the measuring site), type of the region, and the presence of the basement in the building on radon spatial variation, was examined. The analyses have been shown that they significantly affect radon variations but with a relatively small contribution in comparison to the radon variation between district. Furthermore, the significance and contribution of the investigated factors were different in each district, which confirmed the second hypothesis for their spatiality.

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Synthesis, anticancer effect and molecular modeling of new thiazolylpyrazolyl coumarin derivatives targeting VEGFR-2 kinase and inducing cell cycle arrest and apoptosis.

Synthesis, anticancer effect and molecular modeling of new thiazolylpyrazolyl coumarin derivatives targeting VEGFR-2 kinase and inducing cell cycle arrest and apoptosis.

Bioorg Chem. 2019 Jan 03;85:253-273

Authors: Mohamed TK, Batran RZ, Elseginy SA, Ali MM, Mahmoud AE

Abstract
New thiazolylpyrazolyl coumarin derivatives were synthesized and tested for their anticancer potential in vitro against five different human cell lines, including breast MCF-7, lung A549, prostate PC3, liver HepG2 and normal melanocyte HFB4. Breast carcinoma revealed higher sensitivity towards compounds 7a, 8c, 9b, 9c and 9d with IC50 values ranging from 5.41 to 10.75 μM in comparison to the reference drug doxorubicin (IC50 = 6.73 μM). In addition, no noticeable toxicity was exhibited towards normal cells HFB4. Moreover, in vitro studies of the VEGFR-2 inhibition in human breast cancer MCF-7 cell line for the promising cytotoxic compounds showed that compounds 7a, 8c, 9b, 9c and 9d were potent inhibitors at low micromolar concentrations (IC50 = 0.034-0.582 μM) compared to the reference drug, sorafenib (IC50 = 0.019 μM). Several theoretical and experimental studies were done to reveal the molecular mechanisms that control breast carcinoma metastasis. The mechanistic effectiveness in cell cycle progression, apoptotic induction and gene regulation were assessed for the promising compound 9d due to its remarkable cytotoxic activity against MCF-7 and significant VEGFR-2 inhibition. Flow cytometeric analysis showed that compound 9d induced cell growth cessation at G2/M phase and increased the percentage of cells at pre-G1 phase that stimulates the apoptotic death of MCF-7 cells. Furthermore, real time PCR assay illustrated that compound 9d up regulated p53 gene expression and elevated Bax/Bcl-2 ratio which confirmed the mechanistic pathway of compound 9d. Moreover, the apoptotic induction of breast cancer cells MCF-7 was enhanced effectively through activation of caspases-7 and 9 by compound 9d. On the other hand, a set of in silico methods such as molecular docking, molecular dynamics simulation, QSAR analysis as well as ADMET analysis was performed in order to study the protein-ligand interactions and the relationship between the physicochemical properties and the inhibitory activity of the promising compounds 7a, 8c and 9d. Based on the aforementioned findings, compound 9d could be considered as effective apoptosis modulator and promising lead for future development of new anti-breast cancer agents.

PMID: 30641320 [PubMed - as supplied by publisher]

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CircRNA_014511 affects the radiosensitivity of bone marrow mesenchymal stem cells by binding to miR-29b-2-5p.

CircRNA_014511 affects the radiosensitivity of bone marrow mesenchymal stem cells by binding to miR-29b-2-5p.

Bosn J Basic Med Sci. 2019 Jan 14;:

Authors: Wang Y, Zhang J, Li J, Gui R, Nie X, Huang R

Abstract
Hematopoietic stem cell transplantation is commonly used in patients with certain hematological or bone marrow tumors. Total body irradiation combined with chemotherapy is part of the preconditioning protocol that was the most commonly used before hematopoietic stem cell transplantation. However, total body irradiation preconditioning damages other normal cells in bone marrow. Therefore, exploring the mechanism of radiation resistance in bone marrow mesenchymal stem cells is of great significance for recovering the hematopoietic function after cell transplantation. This study aimed to demonstrate the miR-29b adsorption of circRNA_014511 and explore the effect of circRNA_014511 on radiosensitivity of bone marrow mesenchymal stem cells. In this study, circRNA_014511 overexpression vector was constructed and transfected into bone marrow mesenchymal stem cells, miR-29b-2-5p and P53 were found to be decreased, which could be reversed by miR29b-mimics. Dual luciferase reporter assay confirmed the binding of circRNA_014511 and mmu-miR-29b-2-5p. Flow cytometry analysis showed the apoptosis rate of bone marrow mesenchymal stem cells overexpressing circRNA_014511 was significantly decreased. In the circRNA_014511 transfection group, after cells were subjected to 6Gy irradiation, G2 phase arrest appeared, the expression of P21 and GADD45A was significantly decreased, and cyclin B1 was significantly increased. Colony formation assay showed the survival fraction of circRNA_014511 overexpression cells after irradiation was significantly higher than control group, and the radiosensitivity was decreased. In conclusion，our findings demonstrated that circRNA_014511 could inhibit the expression of P53 by binding miR-29b-2-5p, and decrease the radiosensitivity of bone marrow mesenchymal stem cells by affecting cell cycle and cell apoptosis.

PMID: 30640591 [PubMed - as supplied by publisher]

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Budding yeast Rtt107 prevents checkpoint hyperactivation after replicative stress by limiting DNA damage.

Budding yeast Rtt107 prevents checkpoint hyperactivation after replicative stress by limiting DNA damage.

DNA Repair (Amst). 2019 Jan 06;74:1-16

Authors: Brown JAR, Kobor MS

Abstract
Cells respond to DNA damage by activating cell cycle checkpoints, arresting cell division or DNA replication while damage is repaired. In Saccharomyces cerevisiae, activation of the checkpoint kinase Rad53 leads to cell cycle arrest, with Rad53 deactivation required for proper resumption of the cell cycle. Rtt107 is a S. cerevisiae protein that acts as a scaffold in the response to DNA damage, and rtt107Δ mutants exhibit prolonged activation of Rad53 when subjected to replication stress. This phenotype has been attributed to checkpoint dampening, wherein an Rtt107-Slx4-Dpb11 interaction limits formation of a Rad9-Dpb11 complex that promotes Rad53 activation. However, we found that the rtt107Δ mutant contains higher levels of DNA damage during replication stress, presenting an alternative possible cause of Rad53 hyperactivation. We therefore sought to address the relevance of checkpoint dampening to the Rad53 hyperactivation phenotype of the rtt107Δ mutant by using a rad9-ST462,474AA allele that specifically disrupts Rad9-Dpb11 interaction. Incorporation of the rad9-ST462,474AA allele slightly suppressed the rtt107Δ mutant's DNA damage sensitivity phenotypes, while having little effect on Rad53 hyperactivation. This indicated that in the context of acute replication stress, Rad53 hyperactivation in the rtt107Δ mutant did not primarily result from Rad9-Dpb11 interaction. A H2A-S129A mutation, which generally reduces Rad9-mediated Rad53 activation, led to more robust suppression of rtt107Δ mutant phenotypes. Suppression of rtt107Δ mutant DNA damage sensitivity by the H2A-S129A or the rad9-ST462,474AA alleles required intact DNA damage tolerance pathways, indicating a reliance of the rtt107Δ mutant on tolerance pathways for reasons other than misregulation of Rad53 activity. Collectively, this work proposed a revised model of Rad53 hyperactivation after acute replicative stress in the rtt107Δ mutant, in which this phenotype was primarily a consequence of excess DNA damage.

PMID: 30639951 [PubMed - as supplied by publisher]

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Diethyl [(3-phenoxy-2-oxo-4-phenyl-azetidin-1-yl)-phenyl-methyl]-phosphonate as a potent anticancer agent in chemo-differentiation therapy of acute promyelocytic leukemia.

Diethyl [(3-phenoxy-2-oxo-4-phenyl-azetidin-1-yl)-phenyl-methyl]-phosphonate as a potent anticancer agent in chemo-differentiation therapy of acute promyelocytic leukemia.

Eur J Pharmacol. 2019 Jan 10;:

Authors: Mohammadi S, Akbari-Birgani S, Borji M, Kaboudin B, Vaezi M

Abstract
Organophosphonates are a group of chemical agents which have high bioactivity. In the present study, we aimed to investigate the anticancer activity of the synthesized β-lactam derivatives of α-amino phosphonates on solid tumor and human leukemic cell lines. The results show that one of these compounds, Diethyl [(3-phenoxy-2-oxo-4-phenyl-azetidine-1-yl)-phenyl-methyl]-phosphonate, is a potent anticancer agent which especially shows anti-leukemic activity. Flow cytometry study showed that this chemical agent causes the G1 phase cell cycle arrest and consequently apoptosis in NB4 cell line as an acute promyelocytic leukemia model. In fact, this agent induces cell differentiation and apoptosis, at low and high concentrations, respectively. Its combination with All-Trans Retinoic Acid shows a higher percentage of cells in the terminal differentiation stage. This evidence suggested that diethyl phosphonate might be a proper candidate for chemo-differentiation therapy in acute promyelocytic leukemia and even in other types of acute myeloid leukemia.

PMID: 30639798 [PubMed - as supplied by publisher]

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Discovery of Small-Molecule Inhibitors of the HSP90-Calcineurin-NFAT Pathway against Glioblastoma.

Discovery of Small-Molecule Inhibitors of the HSP90-Calcineurin-NFAT Pathway against Glioblastoma.

Cell Chem Biol. 2018 Nov 30;:

Authors: Liu Z, Li H, He L, Xiang Y, Tian C, Li C, Tan P, Jing J, Tian Y, Du L, Huang Y, Han L, Li M, Zhou Y

Abstract
Glioblastoma (GBM) is among the most common and malignant types of primary brain tumors in adults, with a dismal prognosis. Although alkylating agents such as temozolomide are widely applied as the first-line treatment for GBM, they often cause chemoresistance and remain ineffective with recurrent GBM. Alternative therapeutics against GBM are urgently needed in the clinic. We report herein the discovery of a class of inhibitors (YZ129 and its derivatives) of the calcineurin-NFAT pathway that exhibited potent anti-tumor activity against GBM. YZ129-induced GBM cell-cycle arrest at the G2/M phase promoted apoptosis and inhibited tumor cell proliferation and migration. At the molecular level, YZ129 directly engaged HSP90 to antagonize its chaperoning effect on calcineurin to abrogate NFAT nuclear translocation, and also suppressed other proto-oncogenic pathways including hypoxia, glycolysis, and the PI3K/AKT/mTOR signaling axis. Our data highlight the potential for targeting the cancer-promoting HSP90 chaperone network to treat GBM.

PMID: 30639261 [PubMed - as supplied by publisher]

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Cellular senescence, aging, and age-related disease: Special issue of BMB Reports in 2019.

Cellular senescence, aging, and age-related disease: Special issue of BMB Reports in 2019.

BMB Rep. 2019 Jan 14;:

Authors: Lee JS

Abstract
Cellular senescence is a state of permanent cell cycle arrest which exhibits large and flattened morphological characteristics. Cellular senescence might evolve to a beneficial process to suppress the accumulation of severely damaged cells. However, senescent cells are considered as the cause of age-related pathologies and diseases. In contrast replicative senescence, premature senescence could be rapidly induced through intrinsic and extrinsic insults. Cancer cell senescence has been accepted as an alternative and attractive tumor suppressive mechanism. In addition to the non-proliferative aspect, senescence associated with diverse functionality affect tissue homeostasis through the communication with their neighboring cells. Aging is a time-dependent process of deterioration, accompanied by progressive metabolic alteration and accumulation of senescent cells. Aging is the main risk factor for many chronic diseases. Chronic inflammation which is principally induced by senescence associated senescence phenotype (SASP) might be the major underlying cause of many age-related disease. Recently, senotherapeutics, medicines targeting to kill or modulate senescent cells selectively, have been implicated to be novel strategy for aging intervention which is applicable to promote healthy aging and to prevent or treat age-related diseases. This special issue invites one perspective and ten mini-reviews covering various senescence features, gene expression characteristics with aging, therapeutic strategies related with cancer and age-related diseases.

PMID: 30638180 [PubMed - as supplied by publisher]

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Valtrate from Valeriana jatamansi Jones induces apoptosis and inhibits migration of human breast cancer cells in vitro.

Valtrate from Valeriana jatamansi Jones induces apoptosis and inhibits migration of human breast cancer cells in vitro.

Nat Prod Res. 2019 Jan 12;:1-4

Authors: Tian S, Wang Z, Wu Z, Wei Y, Yang B, Lou S

Abstract
Valtrate is a principle compound isolated from Valeriana jatamansi Jones, a traditional Chinese folk medicine originally used to treat various nervous disorders. Here, we found that valtrate exhibited significant anti-cancer activity in vitro, especially in human breast cancer cells, while displayed relatively low cytotoxicity to normal human breast epithelial cells (MCF 10A). Valtrate induced cell cycle arrest at G2/M stage and apoptosis in MDA-MB-231 and MCF-7 cells, with reduced expression of p-Akt (Ser 473), cyclin B1 and caspase 8, and increased expression of p21, p-cdc2, cleaved-caspase 3, cleaved-caspase 7 and poly (ADP-ribose) polymerase (PARP). In addition, valtrate inhibited cell migration through down-regulation of MMP-9 and MMP-2 expression. These results demonstrate that valtrate possesses anti-breast cancer activities via cell cycle arrest, apoptosis, and inhibition of cell migration, thus supporting valtrate as a potential antitumor agent.

PMID: 30638055 [PubMed - as supplied by publisher]

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Anti-cancer effects of CQBTO, a chloroquine and benzo(e)triazine oxide conjugate.

Related Articles

Anti-cancer effects of CQBTO, a chloroquine and benzo(e)triazine oxide conjugate.

Chem Biol Drug Des. 2019 Jan 13;:

Authors: Guo Z, Pei H, Nie J, Hu W, Zhang J, Ding J, Pan S, Li B, Hei TK, Chen W, Zhou G

Abstract
AIM: Autophagy is a self-protective process, and it confers cancer cells resistance against radio-chemotherapeutics. To induce cancer cell death, a series of compounds of 3- ((4-((7-chloroquinolin-4-yl)amino)butyl)amino)- 7-substituted benzo[e][1,2,4] triazine 1-oxide or CQBTO containing two critical chemical groups were designed and synthesized. One compound, BTO, yielded free radicals to trigger autophagy, and the other one, chloroquine (CQ), was an inhibitor of autophagy. We hypothesized that the compounds could kill cancer cells effectively by inducing incomplete autophagy.
METHODS: In vitro cultured non-small cell lung carcinoma cells and primary lung tumors in mice in vivo were used to test the lethal effects of CQBTO on cancer cells and toxicity to normal tissues. Cell viability was examined using the CCK8 assay. Genomic instability was determined with the cytochalasin B-blocked micronucleus assay. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Western blotting and immunofluorescence were used to detect the induction and localization of LC3, a biomarker for autophagy.
RESULTS: Compared with CQ, three CQBTO compounds were lethal to lung cancer cells, and CQBTO-3 was the most effective. The LD50 for CQBTO-3 was 21 μΜ in A549 cells and 21.5 μΜ in Calu-1 cells, which was lower than that of CQBTO-2 or CQBTO-1. Induction of LC3 foci and an increase in the LC3II/LC3I ratio demonstrated the induction of autophagy by CQBTO-3 in A549 cells, whereas no obvious micronuclei or cell cycle arrest was observed. No detectable toxicity to normal mice was observed. CQBTO-3 improved the quality of mouse life, reduced the number and size of existing tumors, and suppressed tumor formation.
CONCLUSION: CQBTO-3 is a potential chemical compound for lung cancer treatment. This article is protected by copyright. All rights reserved.

PMID: 30637976 [PubMed - as supplied by publisher]

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The RUNX1-ETO fusion protein trans-activates c-KIT expression by recruiting histone acetyltransferase P300 on its promoter.

Related Articles

The RUNX1-ETO fusion protein trans-activates c-KIT expression by recruiting histone acetyltransferase P300 on its promoter.

FEBS J. 2019 Jan 13;:

Authors: Chen G, Liu A, Xu Y, Gao L, Jiang M, Li Y, Lv N, Zhou L, Wang L, Yu L, Li Y

Abstract
The oncoprotein RUNX1-ETO is the fusion product of t(8;21)(q22;q22) and constitutes one of the most common genetic alterations in acute myeloid leukemia (AML). Abnormal c-KIT over-expression is considered an independent negative prognostic factor for relapse and survival in t(8;21) AML patients. However, the molecular mechanism of high c-KIT expression in t(8;21) AML remains unknown. In this study, we detected RUNX1-ETO and c-KIT gene expression in AML-M2 patients and verified the over-expression of c-KIT in t(8;21) AML patients. We also found that c-KIT over-expression was a poor prognostic indicator in RUNX1-ETO-positive AML patients, but not in RUNX1-ETO-negative AML patients. We used the dual-luciferase and chromatin immunoprecipitation assays to demonstrate that the RUNX1-ETO protein epigenetically trans-activates c-KIT by binding to the c-KIT promoter and recruiting the histone acetyltransferase, P300, to the c-Kit promoter, elucidating the mechanism of the abnormally increased c-KIT expression in t(8;21) AML patients. Moreover, pharmacologic studies revealed that C646, a P300 inhibitor, could inhibit proliferation, induce apoptosis and arrest cell cycle more effectively in RUNX1-ETO-positive cells than in negative ones. The levels of c-KIT and RUNX1-ETO proteins were also decreased with C646 treatment in RUNX1-ETO-positive cells. These findings suggested that P300 could be a therapeutic target and that C646 could be used as a potential treatment for RUNX1-ETO-positive AML patients. Interestingly, using the dual-luciferase assay, we also found that the binding capacity of RUNX1-ETO9a, a truncated RUNX1-ETO isoform, to the c-KIT promoter was stronger than that of RUNX1-ETO, suggesting RUNX1-ETO9a as another valuable therapeutic target in t(8;21) AML. This article is protected by copyright. All rights reserved.

PMID: 30637949 [PubMed - as supplied by publisher]

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MiRNA-195-5p Functions as a Tumor Suppressor and a Predictive of Poor Prognosis in Non-small Cell Lung Cancer by Directly Targeting CIAPIN1.

Related Articles

MiRNA-195-5p Functions as a Tumor Suppressor and a Predictive of Poor Prognosis in Non-small Cell Lung Cancer by Directly Targeting CIAPIN1.

Pathol Oncol Res. 2019 Jan 12;:

Authors: Zheng J, Xu T, Chen F, Zhang Y

Abstract
Accumulating evidence suggests that microRNAs (miRNAs) has been proven to be a critical regulator in the tumor progression, of which miR-195-5p was reported to function as tumor suppressor in prostate cancer and oral squamous cell carcinoma. However, studies on the clinical significance and biological function of miR-195-5p in non-small cell lung cancer (NSCLC) were still unavailable. Here, we reported that the expression of miR-195-5p was decreased in NSCLC tissues and cell lines. Downregulation of miR-195-5p was significantly associated with TNM stage, tumor size and lymph node metastasis. The Kaplan-Meier survival analysis demonstrated that the survival time of NSCLC patients with high expression of miR-195-5p was longer than those with low expression during the 5-year follow up period (p = 0.0410). COX regression analysis indicated that miR-195-5p expression was an independent prognostic indicator for the survival of NSCLC patients (HR = 2.45, 95% CI: 1.53-4.63; p = 0.007). Results of functional analyses revealed that overexpression of miR-195-5p in A549 cells inhibited cell proliferation, induced cell cycle G0/G1 phase arrest and apoptosis using MTT and flow cytometry analysis. Furthermore, bioinformatics and luciferase reporter assays demonstrated that cytokine-induced apoptosis inhibitor 1 (CIAPIN1), an anti-apoptotic molecule was a direct target of miR-195-5p in NSCLC cells. Meta-analysis based on Oncomine database showed CIAPIN1 was significantly up-regulated in human lung cancer tissues. Consistently, knockdown of CIAPIN1 phenocopied the inhibitory effects of miR-195-5p overexpression in NSCLC cell function. These findings suggest that miR-195-5p could be used as a potential prognostic predictor and tumor suppressor in NSCLC.

PMID: 30637589 [PubMed - as supplied by publisher]

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Adaptation in replicative senescence: a risky business.

Related Articles

Adaptation in replicative senescence: a risky business.

Curr Genet. 2019 Jan 12;:

Authors: Coutelier H, Xu Z

Abstract
Cell proliferation is tightly regulated to avoid propagating DNA damage and mutations, which can lead to pathologies such as cancer. To ensure genome integrity, cells activate the DNA damage checkpoint in response to genotoxic lesions to block cell cycle progression. This surveillance mechanism provides time to repair the damage before resuming cell cycle with an intact genome. When the damage is not repaired, cells can, in some conditions, override the cell cycle arrest and proceed with proliferation, a phenomenon known as adaptation to DNA damage. A subpopulation of adapted cells might eventually survive, but only at the cost of extensive genome instability. How and in which context adaptation operates the trade-off between survival and genome stability is a fascinating question. After a brief review of the current knowledge on adaptation to DNA damage in budding yeast, we will discuss a new role of adaptation in the context of telomerase-negative cells and replicative senescence. We highlight the idea that, in all settings studied so far, survival through adaptation is a double-edged sword as it comes with increased genomic instability.

PMID: 30637477 [PubMed - as supplied by publisher]

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MARCH5 overexpression contributes to tumor growth and metastasis and associates with poor survival in breast cancer.

Related Articles

MARCH5 overexpression contributes to tumor growth and metastasis and associates with poor survival in breast cancer.

Cancer Manag Res. 2019;11:201-215

Authors: Tang H, Peng S, Dong Y, Yang X, Yang P, Yang L, Yang B, Bao G

Abstract
Background: Human MARCH5 is a mitochondrial localized E3 ubiquitin-protein ligase that is critical for the regulation of mitochondrial dynamics. A body of evidence has indicated the close links between unbalanced mitochondrial dynamics and cancers. However, the expression, biological functions, and prognostic significance of MARCH5 in breast cancer (BC) have not been determined.
Materials and methods: The mRNA and protein expressions of MARCH5 were evaluated by quantitative real-time PCR and Western blot analysis in BC cell lines and tumor tissues. Clinical prognostic significance of MARCH5 was assessed in 65 patients with BC. The biological functions of MARCH5 were determined by in vitro cell proliferation, apoptosis, cell cycle, migration and invasion assays, and in vivo tumor growth and metastasis assays through knockdown or overexpression of MARCH5 in BC cells. In addition, the underlying mechanisms by which MARCH5 regulated BC cell growth and metastasis were explored.
Results: MARCH5 was substantially upregulated in BC cells mainly due to the downregulation of miR-30a, which contributed to the poor survival of BC patients. MARCH5 promoted the growth and metastasis of BC cells both in vitro and in vivo by inducing G1-S cell cycle arrest and epithelial-mesenchymal transition. Mechanistic investigations revealed that the oncogenic effect of MARCH5 was mainly mediated by increased mitochondrial fission and subsequent ROS production in BC cells.
Conclusion: Our findings demonstrate that MARCH5 plays a critical oncogenic role in BC cells, which provides experimental evidence supporting MARCH5 as a potential therapeutic target in BC therapy.

PMID: 30636894 [PubMed]

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Tdp1 processes chromate-induced single-strand DNA breaks that collapse replication forks.

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Tdp1 processes chromate-induced single-strand DNA breaks that collapse replication forks.

PLoS Genet. 2018 08;14(8):e1007595

Authors: Ganguly A, Guo L, Sun L, Suo F, Du LL, Russell P

Abstract
Hexavalent chromium [Cr(VI)] damages DNA and causes cancer, but it is unclear which DNA damage responses (DDRs) most critically protect cells from chromate toxicity. Here, genome-wide quantitative functional profiling, DDR measurements and genetic interaction assays in Schizosaccharomyces pombe reveal a chromate toxicogenomic profile that closely resembles the cancer chemotherapeutic drug camptothecin (CPT), which traps Topoisomerase 1 (Top1)-DNA covalent complex (Top1cc) at the 3' end of single-stand breaks (SSBs), resulting in replication fork collapse. ATR/Rad3-dependent checkpoints that detect stalled and collapsed replication forks are crucial in Cr(VI)-treated cells, as is Mus81-dependent sister chromatid recombination (SCR) that repairs single-ended double-strand breaks (seDSBs) at broken replication forks. Surprisingly, chromate resistance does not require base excision repair (BER) or interstrand crosslink (ICL) repair, nor does co-elimination of XPA-dependent nucleotide excision repair (NER) and Rad18-mediated post-replication repair (PRR) confer chromate sensitivity in fission yeast. However, co-elimination of Tdp1 tyrosyl-DNA phosphodiesterase and Rad16-Swi10 (XPF-ERCC1) NER endonuclease synergistically enhances chromate toxicity in top1Δ cells. Pnk1 polynucleotide kinase phosphatase (PNKP), which restores 3'-hydroxyl ends to SSBs processed by Tdp1, is also critical for chromate resistance. Loss of Tdp1 ameliorates pnk1Δ chromate sensitivity while enhancing the requirement for Mus81. Thus, Tdp1 and PNKP, which prevent neurodegeneration in humans, repair an important class of Cr-induced SSBs that collapse replication forks.

PMID: 30148840 [PubMed - indexed for MEDLINE]

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Antiproliferative and antimetastatic properties of 3-benzyloxy-16-hydroxymethylene-estradiol analogs against breast cancer cell lines.

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Antiproliferative and antimetastatic properties of 3-benzyloxy-16-hydroxymethylene-estradiol analogs against breast cancer cell lines.

Eur J Pharm Sci. 2018 Oct 15;123:362-370

Authors: Sinka I, Kiss A, Mernyák E, Wölfling J, Schneider G, Ocsovszki I, Kuo CY, Wang HC, Zupkó I

Abstract
Despite emerging new therapeutic opportunities, cancer is still a major health problem and a leading cause of death worldwide. Breast tumors are the most frequently diagnosed female malignancies, and the triple-negative subtype is associated with poorer prognosis and lower survival rates than other breast cancer types. The aims of the present study were to determine the anticancer potency of a set of C-3 and C-16 modified estradiol-derivatives against a panel of breast cancer cell lines, and to characterize the mechanism of action of two selected compounds (1 and 5) against the MDA-MB-231 triple-negative breast cancer cell line. Growth-inhibitory properties were investigated by an MTT-assay. Cell cycle analysis by flow cytometry has revealed G1 phase accumulation and indicated the proapoptotic effect of 1 and 5 through the elevation of the apoptotic subG1 phase on MDA-MB-231 cells after 24 h treatment. The antimetastatic activities of these compounds were examined by wound healing and Boyden chamber assays, and both compounds were shown to significantly inhibit the migration and invasion of MDA-MB-231 cells at sub-antiproliferative concentrations. Gelatin zymography assay has indicated that matrix metalloproteinase-2 and -9 are not involved in the antimetastatic action of the molecules. Western blot analysis was performed with 24 h incubation to examine the possible changes in the level of focal adhesion kinase (FAK), and both compounds were found to inhibit the phosphorylation of FAK in a concentration-dependent manner in MDA-MB-231 cells. The results of this study demonstrate that C-3 and C-16 modified estradiol derivatives are potent antiproliferative and antimetastatic compounds against a triple-negative breast cancer cell line with a mechanism of action involving the inhibition of FAK, a novel anticancer therapeutic target. Therefore, these findings can be utilized in the development of promising anticancer agents with steroid skeleton.

PMID: 30010030 [PubMed - indexed for MEDLINE]

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Discovery of a dual protease mechanism that promotes DNA damage checkpoint recovery.

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Discovery of a dual protease mechanism that promotes DNA damage checkpoint recovery.

PLoS Genet. 2018 07;14(7):e1007512

Authors: Burby PE, Simmons ZW, Schroeder JW, Simmons LA

Abstract
The DNA damage response is a signaling pathway found throughout biology. In many bacteria the DNA damage checkpoint is enforced by inducing expression of a small, membrane bound inhibitor that delays cell division providing time to repair damaged chromosomes. How cells promote checkpoint recovery after sensing successful repair is unknown. By using a high-throughput, forward genetic screen, we identified two unrelated proteases, YlbL and CtpA, that promote DNA damage checkpoint recovery in Bacillus subtilis. Deletion of both proteases leads to accumulation of the checkpoint protein YneA. We show that DNA damage sensitivity and increased cell elongation in protease mutants depends on yneA. Further, expression of YneA in protease mutants was sufficient to inhibit cell proliferation. Finally, we show that both proteases interact with YneA and that one of the two proteases, CtpA, directly cleaves YneA in vitro. With these results, we report the mechanism for DNA damage checkpoint recovery in bacteria that use membrane bound cell division inhibitors.

PMID: 29979679 [PubMed - indexed for MEDLINE]

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