Synthetic Musk Fragrances in Lake Erie and Lake Ontario Sediment Cores

PubMed Central

Peck, Aaron M.; Linebaugh, Emily K.; Hornbuckle, Keri C.

2009-01-01

Two sediment cores collected from Lake Ontario and Lake Erie were sectioned, dated, and analyzed for five polycyclic musk fragrances and two nitro musk fragrances. The polycyclic musk fragrances were HHCB (Galaxolide), AHTN (Tonalide), ATII (Traseolide), ADBI (Celestolide), and AHMI (Phantolide). The nitro musk fragrances were musk ketone and musk xylene. Chemical analysis was performed by gas chromatography/mass spectrometry (GC/MS) and results from Lake Erie were confirmed using gas chromatography/triple-quadrupole mass spectrometry (GC/MS/MS). The chemical signals observed at the two sampling locations were different from each other due primarily to large differences in the sedimentation rates at the two sampling locations. HHCB was detected in the Lake Erie core while six compounds were detected in the Lake Ontario core. Using measured fragrance and 210Pb activity, the burden of synthetic musk fragrances estimated from these sediment cores is 1900 kg in Lake Erie and 18000 kg in Lake Ontario. The input of these compounds to the lakes is increasing. The HHCB accumulation rates in Lake Erie for 1979-2003 and 1990-2003 correspond to doubling times of 16 ± 4 yr and 8 ± 2 yr, respectively. The results reflect current U.S. production trends for the sum of all fragrance compounds. PMID:17007119

Synthetic musk fragrances in Lake Michigan.

PubMed

Peck, Aaron M; Hornbuckle, Keri C

2004-01-15

Synthetic musk fragrances are added to a wide variety of personal care and household products and are present in treated wastewater effluent. Here we report for the first time ambient air and water measurements of six polycyclic musks (AHTN, HHCB, ATII, ADBI, AHMI, and DPMI) and two nitro musks (musk xylene and musk ketone) in North America. The compounds were measured in the air and water of Lake Michigan and in the air of urban Milwaukee, WI. All of the compounds except DPMI were detected. HHCB and AHTN were found in the highest concentrations in all samples. Airborne concentrations of HHCB and AHTN average 4.6 and 2.9 ng/m3, respectively, in Milwaukee and 1.1 and 0.49 ng/m3 over the lake. The average water concentration of HHCB and AHTN in Lake Michigan was 4.7 and 1.0 ng/L, respectively. A lake-wide annual mass budget shows that wastewater treatment plant discharge is the major source (3470 kg/yr) of the synthetic musks while atmospheric deposition contributes less than 1%. Volatilization and outflow through the Straits of Mackinac are major loss mechanisms (2085 and 516 kg/yr for volatilization and outflow, respectively). Concentrations of HHCB are about one-half the predicted steady-state water concentrations in Lake Michigan.

CLOSED-LOOP STRIPPING ANALYSIS (CLSA) OF ...

EPA Pesticide Factsheets

Synthetic musk compounds have been found in surface water, fish tissues, and human breast milk. Current techniques for separating these compounds from fish tissues require tedious sample clean-upprocedures A simple method for the deterrnination of these compounds in fish tissues has been developed. Closed-loop stripping of saponified fish tissues in a I -L Wheaton purge-and-trap vessel is used to strip compounds with high vapor pressures such as synthetic musks from the matrix onto a solid sorbent (Abselut Nexus). This technique is useful for screening biological tissues that contain lipids for musk compounds. Analytes are desorbed from the sorbent trap sequentially with polar and nonpolar solvents, concentrated, and directly analyzed by high resolution gas chromatography coupled to a mass spectrometer operating in the selected ion monitoring mode. In this paper, we analyzed two homogenized samples of whole fish tissues with spiked synthetic musk compounds using closed-loop stripping analysis (CLSA) and pressurized liquid extraction (PLE). The analytes were not recovered quantitatively but the extraction yield was sufficiently reproducible for at least semi-quantitative purposes (screening). The method was less expensive to implement and required significantly less sample preparation than the PLE technique. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water,

Scented traces--Dermal exposure of synthetic musk fragrances in personal care products and environmental input assessment.

PubMed

Homem, Vera; Silva, Eduardo; Alves, Arminda; Santos, Lúcia

2015-11-01

Synthetic musks are organic compounds used as fragrance and fixative additives in several personal care products. Until now, little is known about their occurrence and distribution in these household commodities. However, this information is essential to perform a human dermal exposure assessment. Therefore, this study gives an overview on the levels of 12 synthetic musks in 140 personal care products from 7 different categories (body and hair wash, toilet soaps, shaving products, dentifrice products, deodorants/antiperspirants, moisturizers and perfumes). They were analysed by QuEChERS extraction followed by gas chromatography-mass spectrometry. Detection limits were found between 0.01ngg(-1) (galaxolide) and 5.00ngg(-1) (musk xylene). Higher average concentrations of total synthetic musks were detected in perfumes (5245.05μgg(-1)) and shampoos (487.67μgg(-1)) for adults. Galaxolide, exaltolide and cashmeran were the most detected compounds. Combining these results with the daily usage amounts, an average daily dermal exposure of 75.69μgkgbw(-1)day(-1) for adults and 15.54μgkgbw(-1)day(-1) for babies/children was achieved. The main contributors for adult and babies/children dermal exposure were perfumes and lotions, respectively. About 40% of the adult daily dermal exposure is related to exaltolide, 30% galaxolide, and 15% tonalide, while for babies/children 96% occurs due to exaltolide. An estimate of the amount of musks discharged "down-the-drain" into the wastewater treatment systems through the use of toiletries was also performed. An average emission per capita of 6.7mgday(-1) was determined and galaxolide and exaltolide were the predominant musks in the effluents. Copyright © 2015 Elsevier Ltd. All rights reserved.

LEVELS OF SYNTHETIC MUSKS COMPOUNDS IN AQUATIC ...

EPA Pesticide Factsheets

Synthetic musk compounds are consumer chemicals manufactured as fragrance materials Due to their high worldwide usage and release, they frequently occur in the aquatic and marine environments. The U.S. EPA (ORD, Las Vegas) developed surface-water monitoring methodology and conducted a one-year monthly monitoring of synthetic musks in water and biota from Lake Mead (Nevada) as well as from combined sewage effluent streams feeding Lake Mead. Presented are the overview of the chemistry, the monitoring methodology, and the significance of synthetic musk compounds in the aquatic environment. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than p

Synthetic musk in seafood products from south Europe using a quick, easy, cheap, effective, rugged and safe extraction method.

PubMed

Saraiva, M; Cavalheiro, J; Lanceleur, L; Monperrus, M

2016-06-01

This study aims at developing a method for the determination of 9 synthetic musk compounds in seafood products by combining the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method and determination by gas chromatography mass spectrometry (GC-EI-MS). Method detection limits (MDL) ranging between 0.001 and 1.94 ng g(-1) were obtained. The linearity is higher than 0.9899 in the range MDL - 100 ng g(-1) with precision below 18% and recoveries between 46% and 120% were obtained. The method was applied to quantify musk compounds in seafood products from the European southwest coast (oysters, mussels, salmon organs, glass eels). Galaxolide and Tonalide exhibited the highest concentration levels ranging between MDL - 96.4 ng g(-1) and MDL - 6.85 ng g(-1), respectively. Contamination levels observed for the two nitro musks (musk xylene and musk ketone) are significantly lower ranging between MDL - 0.6 ng g(-1) and MDL - 0.09 ng g(-1), respectively. Analysis of different organs of salmons showed higher concentrations in liver and gonad than in muscle tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Challenge of false alarms in nitroaromatic explosive detection--a detection device based on surface-enhanced Raman spectroscopy.

PubMed

Wackerbarth, Hainer; Gundrum, Lars; Salb, Christian; Christou, Konstantin; Viöl, Wolfgang

2010-08-10

A challenge in the detection of explosives is the differentiation between explosives and contaminants. Synthetic musk-containing perfumes can cause false alarms, as these perfumes are nitroaromatic compounds, which can be mistaken for trinitro toluene (TNT) by some detectors. We present a detection principle based on surface-enhanced Raman scattering (SERS). A stream of the airborne compounds is focused and resublimated on a cooled nanostructured gold surface. We recorded high-resolution SERS spectra of TNT, musk xylene, and musk ketone. The nitroaromatic compounds can be identified unambiguously by their SERS spectra. Even the dominant bands containing nitro-group scissoring and symmetric stretching modes are significantly shifted by the difference in molecular structure.

Long lasting perfume--a review of synthetic musks in WWTPs.

PubMed

Homem, Vera; Silva, José Avelino; Ratola, Nuno; Santos, Lúcia; Alves, Arminda

2015-02-01

Synthetic musks have been used for a long time in personal care and household products. In recent years, this continuous input has increased considerably, to the point that they were recognized as emerging pollutants by the scientific community, due to their persistence in the environment, and hazardous potential to ecosystems even at low concentrations. The number of studies in literature describing their worldwide presence in several environmental matrices is growing, and many of them indicate that the techniques employed for their safe removal tend to be ineffective. This is the case of conventional activated sludge treatment plants (WWTPs), where considerable loads of synthetic musks enter mainly through domestic sewage. This review paper compiles and discusses the occurrence of these compounds in the sewage, effluents and sludge, main concentration levels and phase distributions, as well as the efficiency of the different methodologies of removal applied in these treatment facilities. To the present day, it has been demonstrated that WWTPs lack the ability to remove musks completely. This shows a clear need to develop new effective and cost-efficient remediation approaches and foresees potential for further improvements in this field. Copyright © 2014 Elsevier Ltd. All rights reserved.

ON-SITE SOLID PHRASE EXTRACTION AND LABORATORY ...

EPA Pesticide Factsheets

Fragrance materials, such as synthetic musks in aqueous samples, are normally analyzed by GC/MS in the selected ion monitoring (SIM) mode to provide maximum sensitivity after liquid-liquid extraction of I -L samples. A I -L sample, however, usually provides too little analyte for full-scan data acquisition. An on-site extraction method for extracting synthetic musks from 60 L of wastewater effluent has been developed. Such a large sample volume permits high-quality, full-scan mass spectra to be obtained for various synthetic musk compounds. Quantification of these compounds was conveniently achieved from the full-scan data directly, without preparing SIM descriptors for each compound to acquire SIM data. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-sol

IN SITU SOLID-PHASE EXTRACTION AND ANALYSIS OF ...

EPA Pesticide Factsheets

Fragrance materials, such as synthetic musks in aqueous samples, are normally analyzed by GC/MS in the selected ion monitoring (SIM) mode to provide maximum sensitivity after liquid-liquid extraction of 1-L samples. A 1-L sample, however, usually provides too little analyte for full-scan data acquisition.We have developed an on-site extraction method for extracting synthetic musks from 60 L of wastewater effluent. Such a large sample volume permits high-quality, full-scan mass spectra to be obtained for various synthetic musk compounds. Quantification of these compounds was conveniently achieved from the full-scan data directly, without preparing SIM descriptors for each compound to acquire SIM data. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-s

Ultrasound-assisted dispersive liquid-liquid microextraction for the determination of synthetic musk fragrances in aqueous matrices by gas chromatography-mass spectrometry.

PubMed

Homem, Vera; Alves, Alice; Alves, Arminda; Santos, Lúcia

2016-01-01

A rapid and simple method for the simultaneous determination of twelve synthetic musks in water samples, using ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) coupled with gas chromatography-mass spectrometry (GC-MS) was successfully developed. The influence of seven factors (volume of the extraction solvent and disperser solvent, sample volume, extraction time, ionic strength, type of extraction and disperser solvent) affecting the UA-DLLME extraction efficiency was investigated using a screening design. The significant factors were selected and optimised employing a central composite design: 80 μL of chloroform, 880 μL of acetonitrile, 6 mL of sample volume, 3.5% (wt) of NaCl and 2 min of extraction time. Under the optimised conditions, this methodology was successfully validated for the analysis of 12 synthetic musk compounds in different aqueous samples (tap, sea and river water, effluent and influent wastewater). The proposed method showed enrichment factors between 101 and 115 depending on the analyte, limits of detection in the range of 0.004-54 ng L(-1) and good repeatability (most relative standard deviation values below 10%). No significant matrix effects were found, since recoveries ranged between 71% and 118%. Finally, the method was satisfactorily applied to the analysis of five different aqueous samples. Results demonstrated the existence of a larger amount of synthetic musks in wastewaters than in other water samples (average concentrations of 2800 ng L(-1) in influent and 850 ng L(-1) in effluent). Galaxolide, tonalide and exaltolide were the compounds most detected. Copyright © 2015 Elsevier B.V. All rights reserved.

New analytical method for the determination of musks in personal care products by Quick, Easy, Cheap, Effective, Rugged, and Safe extraction followed by GC-MS.

PubMed

Homem, Vera; Silva, José Avelino; Cunha, Carina; Alves, Arminda; Santos, Lúcia

2013-07-01

Synthetic musks are organic compounds used as fragrance additives and fixative compounds in a diversity of personal care products. A new method based on quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction followed by GC-MS for the analysis of 12 musks in personal care products was developed and validated. Some experimental parameters, such as total QuEChERS mass, sample mass/solvent volume ratio, type of extraction solvent, as well as salts and sorbents amount were investigated and optimized. The final method involves the musks extraction using acetonitrile, followed by the addition of anhydrous magnesium sulphate and sodium acetate. The clean-up step was performed using dispersive SPE with primary and secondary amine and octadecyl-silica sorbents. This extraction procedure is fast (about 10 min) when compared to other traditional approaches. The method was robust for the matrices studied and shows a high precision (%RSD < 15%) and accuracy (average recovery of 85%), allowing the detection of musks in minimum concentrations between 0.01 ng/g (galaxolide) and 15.80 ng/g (musk xylene). The developed method was applied to the analysis of 12 samples, which revealed musks concentrations ranging from 2 ng/g (toothpaste) to 882,340 ng/g (perfumed body lotion). © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthetic musk emissions from wastewater aeration basins.

PubMed

Upadhyay, Nabin; Sun, Qinyue; Allen, Jonathan O; Westerhoff, Paul; Herckes, Pierre

2011-01-01

Wastewater aeration basins at publicly owned treatment works (POTWs) can be emission sources for gaseous or aerosolized sewage material. In the present study, particle and gas phase emissions of synthetic musks from covered and uncovered aeration basins were measured. Galaxolide (HHCB), tonalide (AHTN), and celestolide (ADBI) were the most abundant, ranging from 6704 to 344,306 ng m(-3), 45-3816 ng m(-3), and 2-148 ng m(-3) in the gas phase with particle phase concentrations 3 orders of magnitude lower. The musk species were not significantly removed from the exhaust air by an odor control system, yielding substantial daily emission fluxes (∼ 200 g d(-1) for HHCB) into the atmosphere. However, simple dispersion modeling showed that the treatment plants are unlikely to be a major contributor to ambient air concentrations of these species. Emission of synthetic musk species during wastewater treatment is a substantial fate process; more than 14% of the influent HHCB is emitted to the atmosphere in a POTW as opposed to the <1% predicted by an octanol-water partition coefficient and fugacity-based US EPA fate model. The substantial atmospheric emission of these compounds is most likely due to active stripping that occurs in the aeration basins by bubbling air through the sludge. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effects of dietary exposure of polycyclic musk HHCB on the metamorphosis of Xenopus laevis.

PubMed

Pablos, María Victoria; Jiménez, María Ángeles; San Segundo, Laura; Martini, Federica; Beltrán, Eulalia; Fernández, Carlos

2016-06-01

The compound 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-[γ]-2-benzopyrane (HHCB; galaxolide, Chemical Abstracts Service number 1222-05-5) is a synthetic musk used extensively as a fragrance in many consumer products and classified as an emerging pollutant. The ecotoxicological information available for HHCB addresses exposure via water, but this compound is frequently adsorbed into particulate matter. The goal of the present study was to assess the effects of dietary exposure to several environmentally relevant HHCB concentrations adsorbed in food during Xenopus laevis metamorphosis. The authors sought to determine if such exposure to this synthetic musk resulted in histological changes in the thyroid gland in conjunction with changes in development (staging, timing to metamorphosis), body weight, and length. Developmental acceleration on day 14, together with hypertrophy of the thyroid follicular epithelium in tadpoles, suggested a possible agonistic effect of HHCB, which would have been compensated after metamorphosis by regulatory mechanisms to maintain homeostasis. Further research into the potential thyroid-related mechanisms of action of HHCB should be conducted. Environ Toxicol Chem 2016;35:1428-1435. © 2015 SETAC. © 2015 SETAC.

ON-SITE SOLID-PHASE EXTRACTION AND LABORATORY ...

EPA Pesticide Factsheets

Fragrance materials such as synthetic musks in aqueous samples, are normally determined by gas chromatography/mass spectrometry in the selected ion monitoring (SIM) mode to provide maximum sensitivity after liquid-liquid extraction of I -L samples. Full-scan mass spectra are required to verify that a target analyte has been found by comparison with the mass spectra of fragrance compounds in the NIST mass spectral library. A I -L sample usually provides insufficient analyte for full scan data acquisition. This paper describes an on-site extraction method developed at the U.S. Environmental Protection Agency (USEPA)- Las Vegas Nevada - for synthetic musks from 60 L of wastewater effluent. Such a large sample volume permits high-quality, full-scan mass spectra to be obtained for a wide array of synthetic musks. Quantification of these compounds was achieved from the full-scan data directly, without the need to acquire SIM data. The detection limits obtained with this method are an order of magnitude lower than those obtained from liquid-liquid and other solid phase extraction methods. This method is highly reproducible, and recoveries ranged from 80 to 97% in spiked sewage treatment plant effluent. The high rate of sorbent-sample mass transfer eliminated the need for a methanolic activation step, which reduced extraction time, labor, and solvent use, More samples could be extracted in the field at lower cost. After swnple extraction, the light- weight cartridges ar

Human exposure to nitro musks and the evaluation of their potential toxicity: an overview

PubMed Central

2014-01-01

Synthetic nitro musks are fragrant chemicals found in household and personal care products. The use of these products leads to direct exposures via dermal absorption, as well as inhalation of contaminated dust and volatilized fragrances. Evidence also suggests that humans are exposed to low doses of these chemicals through oral absorption of contaminated liquids and foods. As these compounds are lipophilic, they and their metabolites, have been found not only in blood, but also breast milk and adipose tissue. After personal use, these environmentally persistent pollutants then pass through sewage treatment plants through their effluent into the environment. Little is known about the biological effects in humans after such a prolonged low dose exposure to these chemicals. While epidemiologic studies evaluating the effects of nitro musk exposures are lacking, there is limited evidence that suggest blood levels of nitro musks are inversely related to luteal hormone levels. This is supported by animal models and laboratory studies that have shown that nitro musks are weakly estrogenic. Nitro musks exposure has been associated with an increased risk of tumor formation in mice. The evidence suggests that while nitro musks by themselves are not genotoxic, they may increase the genotoxicity of other chemicals. However, animal models for nitro musk exposure have proven to be problematic since certain outcomes are species specific. This may explain why evidence for developmental effects in animals is conflicting and inconclusive. Given that animal models and cell-line experiments are suggestive of adverse outcomes, further epidemiologic studies are warranted. PMID:24618224

Identification of Bound Nitro Musk-Protein Adduct in Fish Liver By Gas Chromatography-Mass Sectrometry: Biotransformation, Dose-Response and Toxicokinetics of Nitro Musk Metabolites Protein Adducts in Trout Liver as Biomarker of Exposure

EPA Science Inventory

Ubiquitous occurrences of synthetic nitro musks are evident in the literature. The In vivo analysis of musk xylene (MX) and musk ketone (MK) - protein adducts in trout liver have been performed by gas chromatography-mass spectrometry using selected ion monitoring (GC-SIM-MS). Bio...

Sorption of three synthetic musks by microplastics.

PubMed

Zhang, Xiaojun; Zheng, Minggang; Wang, Ling; Lou, Yinghua; Shi, Lei; Jiang, Shujun

2018-01-01

Microplastics and synthetic musks (SMs) are two typical organic pollutants in the marine environment. In this study, the sorption of three SMs to microplastics in a simulated seawater environment was examined. Tonalide (AHTN), musk xylene (MX), and musk ketone (MK) were the musks investigated, while polypropylene (PP) was used as the microplastic. It was found that the equilibrium sorption time was about 10h and the adsorption kinetics model conformed to a Lagergren adsorption model. The adsorption capacity increased with decreasing particle size. Adsorption reached a peak at 25°C, and the adsorption capacity was not sensitive to the concentration of sodium chloride. There is a need for more research and monitoring of microplastics in the marine environment due to their strong ability to absorb organic pollutants. Copyright © 2017. Published by Elsevier Ltd.

Contribution of Wastewater Treatment Plants to Concentrations of PBDEs, PFCs, PCBs, DDT and Synthetic Musks in Fish Tissue from U.S. Urban Waters

EPA Science Inventory

Wastewater treatment plants (WWTPs) are tasked with removing a wide variety of contaminants from influents, including BOD and nutrients from human waste as well as any and all other compounds that emanate from homes and commercial facilities in the communities they serve. Traces ...

In vitro determination of transdermal permeation of synthetic musks and estimated dermal uptake through usage of personal care products.

PubMed

Zhang, Xiaolan; Yu, Yuling; Gu, Yue; Li, Xiaojing; Zhang, Xinyu; Yu, Yingxin

2017-04-01

Synthetic musks, chemical constituents of personal care products, enter the human body through dermal contact. Elucidation of the mechanisms underlying transdermal permeation of synthetic musks should enhance our understanding of their uptake and distribution in human skin and allow accurate evaluation of associated human exposure. Here, the transdermal permeation dynamics and distribution of galaxolide (HHCB) and tonalide (AHTN) were investigated using an in vitro skin diffusion model. The transdermal permeation amounts of HHCB and AHTN increased rapidly during the first 6 h. The applied HHCB and AHTN amounts did not affect percutaneous absorption rates. HHCB and AHTN remained primarily in the stratum corneum, accounting for 70.0% and 70.3% of the totals during the 24-h period, respectively. The percutaneous absorption rate of both chemicals was ∼11%. HHCB, AHTN, musk ketone, musk xylene, and Musk-T were detected in 29 personal care products. The average total concentrations of the musks were 3990, 54.0, 17.7, and 9.8 μg g -1 in perfume, shampoo, lotion, and shower gel, respectively. Among the four product categories, HHCB was dominant (57.4%-99.6%), followed by AHTN. The data clearly indicate that polycyclic and nitro musks are most commonly used in personal care products. The total estimated dermal intake (51.6 μg kg -1 bw  day -1 ) was markedly higher than total dermal uptake (5.9 μg kg -1 bw  day -1 ) when percutaneous absorption rates of the chemicals were added into the calculation. Uptake of HHCB and AHTN via dermal contact of personal care products was significantly higher than that from dust inhalation calculated according to earlier literature data. Copyright © 2017 Elsevier Ltd. All rights reserved.

NITRO MUSK BOUND TO CARP HEMOGLOBIN ...

EPA Pesticide Factsheets

Nitroaromatic compounds including synthetic nitro musks are important raw materials and intermediates in the synthesis of explosives, dyes, and pesticides, pharmaceutical and personal care-products (PPCPs). The nitro musks such as musk xylene (MX) and musk ketone (MK) are extensively used as fragrance ingredients in PPCPs and other commercial toiletries. Identification and quantification of a bound 4-amino-MX (4-AMX) metabolite as well as a 2- amino-MK (2-AMK) metabolite were carried out by gas chromatography-mass spectrometry' (GC/MS), with selected ion monitoring (SIM) in both the electron ionization (ElMS) and electron capture (EC) negative ion chemical ionization (NICIMS) modes. Detection of 4-AMX and 2-AMK occurred after the cysteine adducts in carp hemoglobin, derived from the nitroso metabolites, were released by alkaline hydrolysis. The released metabolites were extracted into n-hexane. The extract was preconcentrated by evaporation, and analyzed by GC-SIM-MS. A comparison between the El and EC approaches was made. EC NICIMS detected both metabolites whereas only 4-AMX was detected by ElMS. The EC NICIMS approach exhibited fewer matrix responses and provided a lower detection limit. Quantitation in both approaches was based on internal standard and a calibration plot. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Q

ON SITE SOLID-PHASE EXTRACTION AND LABORATORY ANALYSIS OF ULTRA-TRACE SYNTHETIC MUSKS IN MUNICIPAL SEWAGE EFFLUENT USING GAS CHROMATOGRAPHY-MASS SPECTROMETRY. FULL-SCAN MODE

EPA Science Inventory

Fragrance materials such as synthetic musks in aqueous samples, are normally determined by gas chromatography/mass spectrometry in the selected ion monitoring (SIM) mode to provide maximum sensitivity after liquid-liquid extraction of I -L samples. Full-scan mass spectra are requ...

OPPT workplan risk assessment 1,3,4,6,7,8-Hexahydro-4,6,6 ...

EPA Pesticide Factsheets

HHCB (Galaxolide) is a synthetic polycyclic musk used as an ingredient in a wide range of consumer products including perfumes, cosmetics, shampoos, lotions, detergents, fabric softeners, and cleaning agents. It is one of the largest-volume chemicals of the polycyclic musks and is imported into the U.S. by 4 known importers. HHCB is considered one of the more important compounds to the fragrance industry because, as a musk, it imparts unique odor properties, has the ability to improve the fixation of fragrance compounds, and binds fragrances to fabrics. The assessment will focus on environmental risk due to release of HHCB to the aquatic and terrestrial environment from all combined uses. Human health risks have been evaluated previously and will be summarized in this assessment. EPA anticipates issuing draft risk assessments for public review and comment as they are completed. At the conclusion of the review process, if an assessment of specific uses indicates significant risk, EPA will evaluate and pursue appropriate risk reduction actions, as warranted. If an assessment indicates no significant risk, EPA will conclude its current work on assessment of those specified targeted uses of that chemical. Over time, additional chemicals will be added to the work plan as more data are developed and more chemicals screened.

IN SITU SOLID-PHASE EXTRACTION AND ANALYSIS OF ULTRA-TRACE SYNTHETIC MUSKS IN MUNICIPAL SEWAGE EFFLUENT USING GAS CHROMATOGRAPHY-MASS SPECTROMETRY, FULL-SCAN MODE

EPA Science Inventory

Fragrance materials, such as synthetic musks in aqueous samples, are normally analyzed by GC/MS in the selected ion monitoring (SIM) mode to provide maximum sensitivity after liquid-liquid extraction of 1-L samples. A 1-L sample, however, usually provides too little ana...

ON-SITE SOLID PHRASE EXTRACTION AND LABORATORY ANALYSIS OF ULTRA-TRACE SYNTHETIC MUSKS IN MUNICIPAL SEWAGE EFFLUENT USING GAS CHROMATOGRAPHY-MASS SPECTROMETRY, FULL-SCAN MODE

EPA Science Inventory

Fragrance materials, such as synthetic musks in aqueous samples, are normally analyzed by GC/MS in the selected ion monitoring (SIM) mode to provide maximum sensitivity after liquid-liquid extraction of I -L samples. A I -L sample, however, usually provides too little ana...

ON-SITE SOLID-PHASE EXTRACTION AND LABORATORY ANALYSIS OF ULTRA-TRACE SYNTHETIC MUSKS IN MUNICIPAL SEWAGE EFFLUENT USING GAS CHROMATOGRAPHY-MASS SPECTROMETRY IN THE FULL-SCAN MODE

EPA Science Inventory

Fragrance materials such as synthetic musks in aqueous samples, are normally determined by gas chromatography/mass spectrometry in the selected ion monitoring (SIM) mode to provide maximum sensitivity after liquid-liquid extraction of I -L samples. Full-scan mass spectra are requ...

MONITORING SYNTHETIC MUSK COMPOUNDS IN ...

EPA Pesticide Factsheets

Synthetic musk compounds are manufactured as fragrance materials for consumer products and are consumed in very large quantities worldwide. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than parts per billion, ppb). IAG with USGS ends in FY05. APM 20 due in FY05.Subtask 2: Coordination of interagency research and public outreach activities for PPCPs. Participate on NSTC Health and Environment subcommittee working group on PPCPs. Web site maintenance and expansion, invited technical presentations, invited articles for peer-reviewed journals, interviews for media, responding to public inquiries. Subtask 3: To apply state-of-the-art envir

Influence of pre-treatment process on matrix effect for the determination of musk fragrances in fish and mussel.

PubMed

Vallecillos, Laura; Pocurull, Eva; Borrull, Francesc

2015-03-01

Musk compounds are widely used as fragrances in personal care products. On account of their widespread use and their low biodegradation, they can be found in environmental samples. In our study two extraction methodologies were compared and different clean-up strategies were also studied in order to develop a reliable analytical method, with minimum matrix effect and good detection limits, to determine synthetic musk fragrances- six polycyclic musks, three nitro musks and the degradation product of one polycyclic musk- in fish and mussel samples. The first extraction technique involves a QuEChERS extraction, a consolidate extraction methodology in the field of food analysis of growing interest over recent years, followed by a dispersive solid-phase extraction (dSPE) as clean-up strategy. The second extraction technique consists of a conventional pressurised liquid extraction (PLE) with dichloromethane and an in-cell clean-up to decrease the matrix effect and remove the undesired components(⁎)present in PLE extracts. Large volume injection (LVI) followed by gas chromatography-ion trap-tandem mass spectrometry (GC-IT-MS/MS) was chosen as the separation and detection technique. Validation parameters, such as method detection limits and method quantification limits were found at ng g(-1) levels for both fish and mussel matrices. Good levels of intra-day and inter-day repeatabilities were obtained analysing fish and mussel samples spiked at 50 ng g(-1) (d.w.) (n=5, RSDs<17%). The developed PLE/GC-IT-MS/MS method was successfully applied to determine the target musk fragrances present in fish and mussel samples from the local market in Tarragona and fish samples from the Ebro River. The results showed the presence of galaxolide (2.97-18.04 ng g(-1) (d.w.)) and tonalide (1.17-8.42 ng g(-1) (d.w.)) in all the samples analysed, while the remaining polycyclic musks such as cashmeran, celestolide and phantolide, were only detected in some of the fish samples analysed. None of the samples analysed contained detectable traces of the nitro musks studied. Copyright © 2014 Elsevier B.V. All rights reserved.

Toxicity of synthetic musks to early life stages of the freshwater mussel Lampsilis cardium

USGS Publications Warehouse

Gooding, M.P.; Newton, T.J.; Bartsch, M.R.; Hornbuckle, K.C.

2006-01-01

Polycyclic musk fragrances are common additives to many consumer products. As a result of their widespread use and slow degradation rates, they are widely found in aquatic environments. This study reports on the lethal and sublethal toxicity of the polycyclic musks AHTN (Tonalide??) and HHCB (Galaxolide??) to glochidial (larval) and juvenile life stages of the freshwater mussel Lampsilis cardium (Rafinesque, 1820). In glochidia, 24-h median lethal concentrations (LC50s) ranged from 454 to 850 ??g AHTN/L and from 1000 to >1750 ??g HHCB/L (water solubility). Results for 48-h tests were similar to the 24-h tests. In 96-h tests with juveniles, we did not observe a dose-response relation between mortality and either musk. However, the growth rate was reduced by musk exposure. The median effective concentrations (EC50s, based on growth) were highly variable and ranged from 108 to 1034 ??g AHTN/L and 153 to 831 ??g HHCB/L. While all adverse effects occurred at concentrations that are much greater than those reported in natural waters (low ??g/L to ng/L), these results indicate the potential for adverse effects on these long-lived organisms from exposure to synthetic musk fragrances. ?? 2006 Springer Science+Business Media, Inc.

Toxicity of Synthetic Musks to Early Life Stages of the Freshwater Mussel Lampsilis cardium

PubMed Central

Gooding, M.P.; Newton, T.J.; Bartsch, M.R.; Hornbuckle, K.C.

2009-01-01

Polycyclic musk fragrances are common additives to many consumer products. As a result of their widespread use and slow degradation rates, they are widely found in aquatic environments. This study reports on the lethal and sublethal toxicity of the polycyclic musks AHTN (Tonalide®) and HHCB (Galaxolide®) to glochidial (larval) and juvenile life stages of the freshwater mussel Lampsilis cardium (Rafinesque, 1820). In glochidia, 24-h median lethal concentrations (LC50s) ranged from 454 to 850 μg AHTN/L and from 1000 to >1750 μg HHCB/L (water solubility). Results for 48-h tests were similar to the 24-h tests. In 96-h tests with juveniles, we did not observe a dose-response relation between mortality and either musk. However, growth rate was reduced by musk exposure. The median effective concentrations (EC50s, based on growth) were highly variable and ranged from 108 to 1034 μg AHTN/L and 153 to 831 μg HHCB/L. While all adverse effects occurred at concentrations that are much greater than those reported in natural waters (low μg/L to ng/L), these results indicate the potential for adverse effects on these long-lived organisms from exposure to synthetic musk fragrances. PMID:16944041

FATE OF SYNTHETIC MUSK COMPOUNDS IN AN AQUATIC ...

EPA Pesticide Factsheets

To be presented is an overview of the chemistry, the monitoring methodology, and the statistical evaluation of concentrations obtained from the analysis of a suite of these compounds (e.g., Galaxolide®, musk xylene, and amino musk xylene) in different environmental compartments. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than parts per billion, ppb). IAG with USGS ends in FY05. APM 20 due in FY05.Subtask 2: Coordination of interagency research and public outreach activities for PPCPs. Participate on NSTC Health and Environment subcommittee working group on PPCPs. Web site maintenance and expansion, invited technical presentations,

LEVELS OF SYNTHETIC MUSK COMPOUNDS IN ...

EPA Pesticide Factsheets

To be presented is an overview of the chemistry, the monitoring methodology, and the statistical evaluation of concentrations obtained from the analysis of a suite of compounds (e.g., Galaxolide®, musk xylene, and amino musk xylene) in an aquatic ecological site. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than parts per billion, ppb). IAG with USGS ends in FY05. APM 20 due in FY05.Subtask 2: Coordination of interagency research and public outreach activities for PPCPs. Participate on NSTC Health and Environment subcommittee working group on PPCPs. Web site maintenance and expansion, invited technical presentations, invited articles

Optimization of a sensitive method for the determination of nitro musk fragrances in waters by solid-phase microextraction and gas chromatography with micro electron capture detection using factorial experimental design.

PubMed

Polo, Maria; Garcia-Jares, Carmen; Llompart, Maria; Cela, Rafael

2007-08-01

A solid-phase microextraction method (SPME) followed by gas chromatography with micro electron capture detection for determining trace levels of nitro musk fragrances in residual waters was optimized. Four nitro musks, musk xylene, musk moskene, musk tibetene and musk ketone, were selected for the optimization of the method. Factors affecting the extraction process were studied using a multivariate approach. Two extraction modes (direct SPME and headspace SPME) were tried at different extraction temperatures using two fiber coatings [Carboxen-polydimethylsiloxane (CAR/PDMS) and polydimethylsiloxane-divinylbenzene (PDMS/DVB)] selected among five commercial tested fibers. Sample agitation and the salting-out effect were also factors studied. The main effects and interactions between the factors were studied for all the target compounds. An extraction temperature of 100 degrees C and sampling the headspace over the sample, using either CAR/PDMS or PDMS/DVB as fiber coatings, were found to be the experimental conditions that led to a more effective extraction. High sensitivity, with detection limits in the low nanogram per liter range, and good linearity and repeatability were achieved for all nitro musks. Since the method proposed performed well for real samples, it was applied to different water samples, including wastewater and sewage, in which some of the target compounds (musk xylene and musk ketone) were detected and quantified.

Assessing the removal of pharmaceuticals and personal care products in a full-scale activated sludge plant.

PubMed

Salgado, R; Marques, R; Noronha, J P; Carvalho, G; Oehmen, A; Reis, M A M

2012-06-01

This study aimed to investigate the removal mechanisms of pharmaceutical active compounds (PhACs) and musks in a wastewater treatment plant (WWTP). Biological removal and adsorption in the activated sludge tank as well as the effect of UV radiation used for disinfection purposes were considered when performing a mass balance on the WWTP throughout a 2-week sampling campaign. Solid-phase extraction (SPE) was carried out to analyse the PhACs in the influent and effluent samples. Ultrasonic solvent extraction was used before SPE for PhACs analysis in sludge samples. PhAC extracts were analysed by LC-MS. Solid-phase microextraction of liquid and sludge samples was used for the analysis of musks, which were detected by GC-MS. The fluxes of the most abundant compounds (13 PhACs and 5 musks) out of 79 compounds studied were used to perform the mass balance on the WWTP. Results show that incomplete removal of diclofenac, the compound that was found in the highest abundance, was observed via biodegradation and adsorption, and that UV photolysis was the main removal mechanism for this compound. The effect of adsorption to the secondary sludge was often negligible for the PhACs, with the exceptions of diclofenac, etofenamate, hydroxyzine and indapamide. However, the musks showed a high level of adsorption to the sludge. UV radiation had an important role in reducing the concentration of some of the target compounds (e.g. diclofenac, ibuprofen, clorazepate, indapamide, enalapril and atenolol) not removed in the activated sludge tank. The main removal mechanism of PhACs and musks studied in the WWTP was most often biological (45%), followed by adsorption (33%) and by UV radiation (22%). In the majority of the cases, the WWTP achieved >75% removal of the most detected PhACs and musks, with the exception of diclofenac.

OPPT workplan risk assessment 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8,-hexamethylcyclopenta[g]-2-benzopyran (HHCB) (CASRN 1222-05-5)

EPA Science Inventory

HHCB (Galaxolide) is a synthetic polycyclic musk used as an ingredient in a wide range of consumer products including perfumes, cosmetics, shampoos, lotions, detergents, fabric softeners, and cleaning agents. It is one of the largest-volume chemicals of the polycyclic musks and i...

Determination of musks and other fragrance compounds at ng/L levels using CLSA (closed loop stripping analysis) and GC/MS detection.

PubMed

Mitjans, D; Ventura, F

2004-01-01

Closed loop stripping analysis (CLSA), a suitable tool for the determination of volatile and semivolatile compounds at low trace levels (ng/l), has been used to determine and quantify seven selected musks and two fragrances (Acetyl cedrene and Amberonne). The obtained extracts are analyzed by high resolution gas chromatography coupled to mass spectrometry (GC/MS) operating in the SIM mode. Quality parameters such as limit of detection; matrix effects; precision expressed as repeatability and reproducibility relative standard deviations of the method and an estimation of the uncertainty have been evaluated. The method has been applied to the analysis of wastewater effluents, surface water and tap water from different places in Europe. All samples contained differents musks at ng/l levels with the polycyclic musks Galaxolide and Tonalide and both fragrances, Amberonne and Acetyl cedrene, being the most abundant. These results suggest the importance of studying and controlling the presence of these ubiquitous environmental compounds in water systems.

Occurrence of synthetic musks in human breast milk samples from 12 provinces in China.

PubMed

Yin, Jie; Wang, Hao; Li, Jingguang; Wu, Yongning; Shao, Bing

2016-07-01

The levels of 12 synthetic musks and one musk metabolite in 24 pooled human milk samples were examined in order to assess the health risks of these contaminants to breast-feeding infants of China. The 24 pooled samples comprised of 1237 individual human milk samples collected from 12 provinces of China according to WHO guidelines. Among the 13 target analytes, OTNE ([1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethylnaphthalen-2yl]ethan-1-one), HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[γ]-2-benzopyran), AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene), musk ketone (4-tert-butyl-2,6-dimethyl-3,5-dinitroacetophenone, MK), Musk T (1,4-dioxacyclohepta decane-5,17-dione), HHCB-lactone (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl cyclopenta[γ]-2-benzopyran-1-one) and musk ambrette (1-(1,1-dimethylethyl)-2-methoxy-4-methyl-3,5-dinitrobenzene, MA), were found in the milk samples analysed with mean (median) concentrations of 3.96 (3.91), 18.03 (15.10), 10.30 (9.38), 4.68 (4.45), < 3.70 (< 3.70), 10.02 (9.20) and < 5.20 (< 5.20) ng g(-1) lipid weight, respectively, whereas ADBI (4-acetyl-1,1-dimethyl-6-tert-butylindan), AHDI (6-acetyl-1,1,2,3,3,5-hexamethylindan), ATII (5-acetyl-1,1,2,6-tetramethyl-3-isopropylindan), musk xylene (1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene, MX), musk tibetene (1-tert-butyl-3,4,5-trimethyl-2,6-dinitrobenzene, MT) and musk moskene (1,1,3,3,5-pentamethyl-4,6-dinotroindane, MM) were not detected. Significantly positive associations were observed in concentration levels between HHCB and AHTN (p < 0.001), HHCB and HHCB-lactone (p < 0.05), AHTN and HHCB-lactone (p < 0.001), and MK and OTNE (p < 0.05). No statistical difference was found in musk concentrations between rural and urban areas in China (p > 0.05). The mean (median) estimated daily intakes by infants were 20.5 (20.2), 93.4 (78.2), 53.4 (48.6), 24.2 (23.0) and 51.9 (47.6) ng kg(-1) body weight for OTNE, HHCB, AHTN, MK and HHCB-lactone, respectively. The musk exposure levels of infants in China via breast feeding were very low according to the current toxicological information.

Energy efficiency for the removal of non-polar pollutants during ultraviolet irradiation, visible light photocatalysis and ozonation of a wastewater effluent.

PubMed

Santiago-Morales, Javier; Gómez, María José; Herrera-López, Sonia; Fernández-Alba, Amadeo R; García-Calvo, Eloy; Rosal, Roberto

2013-10-01

This study aims to assess the removal of a set of non-polar pollutants in biologically treated wastewater using ozonation, ultraviolet (UV 254 nm low pressure mercury lamp) and visible light (Xe-arc lamp) irradiation as well as visible light photocatalysis using Ce-doped TiO2. The compounds tracked include UV filters, synthetic musks, herbicides, insecticides, antiseptics and polyaromatic hydrocarbons. Raw wastewater and treated samples were analyzed using stir-bar sorptive extraction coupled with comprehensive two-dimensional gas chromatography (SBSE-CG × GC-TOF-MS). Ozone treatment could remove most pollutants with a global efficiency of over 95% for 209 μM ozone dosage. UV irradiation reduced the total concentration of the sixteen pollutants tested by an average of 63% with high removal of the sunscreen 2-ethylhexyl trans-4-methoxycinnamate (EHMC), the synthetic musk 7-acetyl-1,1,3,4,4,6-hexamethyltetrahydronaphthalene (tonalide, AHTN) and several herbicides. Visible light Ce-TiO2 photocatalysis reached ~70% overall removal with particularly high efficiency for synthetic musks. In terms of power usage efficiency expressed as nmol kJ(-1), the results showed that ozonation was by far the most efficient process, ten-fold over Xe/Ce-TiO2 visible light photocatalysis, the latter being in turn considerably more efficient than UV irradiation. In all cases the efficiency decreased along the treatments due to the lower reaction rate at lower pollutant concentration. The use of photocatalysis greatly improved the efficiency of visible light irradiation. The collector area per order decreased from 9.14 ± 5.11 m(2) m(-3) order(-1) for visible light irradiation to 0.16 ± 0.03 m(2) m(-3) order(-1) for Ce-TiO2 photocatalysis. The toxicity of treated wastewater was assessed using the green alga Pseudokirchneriella subcapitata. Ozonation reduced the toxicity of treated wastewater, while UV irradiation and visible light photocatalysis limited by 20-25% the algal growth due to the accumulation of reaction by-products. Three transformation products were identified and tracked along the treatments. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sorption and bioaccumulation behavior of multi-class hydrophobic organic contaminants in a tropical marine food web.

PubMed

Zhang, Hui; Kelly, Barry C

2018-05-01

While numerous studies have demonstrated the environmental behavior of legacy persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), information regarding sorption and bioaccumulation potential of other widely used organic chemicals such as halogenated flame retardants (HFRs) is limited. This study involved a comprehensive field investigation of multi-class hydrophobic organic contaminants (HOCs) in environmental media and fish in Singapore Strait, an important tropical maritime strait in Southeast Asia. In total, 90 HOCs were analyzed, including HFRs, synthetic musks, PCBs, OCPs, as well as triclosan and methyl triclosan. The results show that the organic carbon normalized sediment-seawater distribution ratios (C SED /C WD ) of the studied compounds are comparable to the organic carbon-water partition coefficients (K OC ), over a log K OC range of approximately 4-11. The observed species-specific bioaccumulation factors (BAFs), biota-sediment accumulation factors (BSAFs), organism-environment media fugacity ratios (f FISH /f WD and f FISH /f SED ) and trophic magnification factors (TMFs) indicate that legacy POPs and PBDE 47 show bioaccumulation behavior in this tropical marine ecosystem, while triclosan, tonalide, dodecachlorodimethanodibenzocyclooctane stereoisomers (DDC-COs), and hexabromocyclododecanes (HBCDDs) do not. Methyl triclosan and galaxolide exhibit moderate biomagnification. Tetrabromobisphenol A (TBBPA) and 1,2-bis (2,4,6-tribromophenoxy)ethane (BTBPE) were detected in environmental media but not in any of the organisms, suggesting low bioaccumulation potential of these flame retardants. The apparently low bioaccumulation potential of the studied HFRs and synthetic musks is likely because of metabolic transformation and/or reduced bioavailability due to the hydrophobic nature of these compounds. Copyright © 2018 Elsevier Ltd. All rights reserved.

Steroid profile and IRMS analysis of musk administration for doping control.

PubMed

Wang, Jingzhu; He, Yi; Liu, Xin; Yang, Zhiyong; Yang, Wenning

2017-11-01

Musk, the dried secretion of the musk pod (sac) of adult male musk deer, has been used as traditional Chinese Medicine (TCM) in China and south-east Asian countries for thousands of years. Due to the anabolic steroid component in this TCM, musk preparations have been included in the list of medical products containing prohibited substances employed for doping by the State Food and Drug Administration of China. The application of musk pod formulation was claimed to be responsible for some adverse analytical findings (AAFs) in the 2011 FIFA Women's World Cup. Our preliminary study has suggested that musk ingestion did not lead to AAFs of doping control with the single dosage of 100 mg. However, the influences of musk administration in large and multi dosage are still unclear. The aim of this study is to further investigate the influences of musk administration for doping control. Wild and domestic deer musk samples were collected. The concentrations and δ 13 C-values of steroids in musk were analyzed. In an excretion study, 200 and 100 mg of wild and domestic deer musk samples were administrated by 29 subjects, respectively. Fluctuations in steroid profile could be observed, and the ratio of 5α-androstane-3α,17β-diol to 5β-androstane-3α,17β-diol was more sensitive than other parameters. In the IRMS test, the ∆Δδ 13 C-value between endogenous reference compound and etiocholanolone was a sensitive parameter, and AAFs were obtained. It is the first time to confirm with excretion study that musk administration could lead to positive result of doping control. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Analytical Determination of KDOC-Values of Polycyclic Musk Compounds with HS-SPME and GC/MS/MS

NASA Astrophysics Data System (ADS)

Böhm, L.; Düring, R.-A.

2009-04-01

Polycyclic musk compounds, used as fragrances in cosmetics and detergents, get into rivers via domestic wastewater and sewage treatment plants and with sewage sludge as fertilizer into soils. Because of their persistence and lipophilic character they accumulate in biota, so they are pollutants with environmental relevance. The coefficient KDOC is used to quantify the distribution of substances between aqueous phase and dissolved organic matter (DOM) which is quantified by the determination of dissolved organic carbon (DOC). DOM is of specific relevance for the transport and fate of persistent and lipophilic compounds in the environment. The affinity to DOM increases, the more lipophilic a substance is. So the environmental mobility is enhanced with increasing binding on DOM. For that reason, measured KDOC-values are important to predict the fate and behaviour of chemicals in the environment and should be used for environmental fate modelling purposes. LITZ ET AL. (2007) state that, to carry out a risk-assessment for polycyclic musk compounds, further research on their sorption-behaviour is necessary. For the determination of KDOC-values, different concentrations of humic acid were spiked with a multi-component stock solution. The samples were analysed with headspace solid-phase microextraction in combination with gas chromatography coupled with mass spectrometry (HS-SPME GC/MS/MS). The KDOC-values were calculated according to YABUTA ET AL. (2004). The method was validated with single substance stock solutions and with polycyclic aromatic hydrocarbons (PAHs). The results show that the method is applicable, repeatable and suitable to get KDOC-values for many substances very fast, cheap and solvent-free. With our results KDOC-values for polycyclic musk compounds were determined for the first time. Literature LITZ, N. TH., MüLLER, J. AND BöHMER, W. (2007): Occurrence of Polycyclic Musks in Sewage Sludge and their Behaviour in Soils and Plants. Part 2: Investigation of Polycyclic Musks in Soils and Plants. J Soils Sediments 7: 36-44 YABUTA, H., FUKUSHIMA, M., TANAKA, F., ICHIKAWA, H. AND TATSUMI, K. (2004): Solid-phase Microextraction for the Evaluation of Partition Coefficients of a Chlorinated Dioxin and Hexachlorobenzene into Humic Substances. Anal. Sci. 20: 787-791

Determination of fragrances at ng/L levels using CLSA and GC/MS detection.

PubMed

Mitjans, D; Ventura, F

2005-01-01

Polycyclic and nitro musks and two fragrances (Acetyl cedrene and Amberonne) have been determined and quantified in influent and effluent waste water, river water and tap water samples from different European countries by closed loop stripping analysis (CLSA) as a method of preconcentration and GC/MS operating in the SIM mode. Limits of detection; precision expressed as repeatability and reproducibility relative standard deviations of the method; matrix effects and the estimation of the uncertainty have been evaluated. All samples contained different musks at ng/l levels being the polycyclic musks Galaxolide and Tonalide and both fragrances, Amberonne and Acetyl cedrene the most abundant. Removal of these main compounds is achieved partially in all waste water treatment plants studied. These results suggest the importance of studying and controlling the presence of these ubiquitous environmental compounds in water systems.

77 FR 46377 - Foreign-Trade Zone 37-Orange County, NY, Notification of Proposed Production Activity, Takasago...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-03

...-jasmone; citronellol-L; trepanol; menthol; musk; oxalide; perilla oil; cyclohexyl lactone; hotact VBE; santalex T; heliotropyl acetate; ambretone; menthol-L synthetic flakes; citral natural; citronellyl formate...

[Model simulation of the transportation, transformation and accumulation of synthetic musks in soils input through recycle water irrigation].

PubMed

Wang, Mei-E; Chen, Wei-Ping; Jiao, Wen-Tao

2012-12-01

Environmental pollution of synthetic musks HHCB and AHTN, one type of PPCPs, have been attracted great attentions in latest years. One of the main input pathways of HHCB/AHTN to soils is reclaimed water irrigation. In this study, we monitored HHCB and AHTN in soils irrigated by reclaimed water and irrigation water and modeled the transportation and accumulation of HHCB and AHTN in soils using HYDRUS-1D. Results showed that concentrations of HHCB and AHTN in soils irrigated by recycling water were 5 times higher than tape water irrigation soils although both of the concentrations are trace. The temporal increase of accumulation was exponential when lgK(oc) value was 3.44, while linear when lgK(oc) were 4.12 and 4.86. Changes of half life of HHCB/AHTN did not affect their accumulation in surface soils. The downward transportation of HHCB and AHTN under recycling water irrigation was very slow. After 40 years of irrigation, it could only 53 cm at most favored conditionals. The downward movement was greatly impacted by the lgK(oc) values. The dissipation of those two synthetic musks through biological degradation and plant uptake were tiny. The highest dissipation rate through biological degradation and plant uptake was only 7.69% of the total input by reclaimed water irrigation after 40 years. The dissipation rate was increased with the decrease of lgK(oc) values and irrigation time. Results of this work may offer base for accurate assessing the ecological risks of HHCB and AHTN in soils caused by reclaimed water irrigation.

Implausibility of the vibrational theory of olfaction

DOE PAGES

Block, Eric; Ertem, Mehmed Z.; Jang, Seogjoo; ...

2015-04-21

The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. Here, we find no evidence for such differentiation at the molecular level. In fact, we find that the human musk-recognizing receptor, OR5AN1, identified using a heterologous OR expression system and robustly responding to cyclopentadecanone and muscone, fails to distinguish isotopomers of thesemore » compounds in vitro. Furthermore, the mouse (methylthio)methanethiol (MTMT)-recognizing receptor, MOR244-3, and other selected human and mouse ORs, responded similarly to normal, deuterated, and ¹³C isotopomers of their respective ligands, paralleling our results with the musk receptor OR5AN1. These findings suggest that the proposed vibration theory does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other ORs examined. Also, contrary to the vibration theory predictions, muscone-d₃₀ lacks the 1,380-1,550 cm⁻¹ IR bands claimed to be essential for musk odor. Furthermore, our theoretical analysis shows that the proposed electron transfer mechanism of the vibrational frequencies of odorants could be easily suppressed by quantum effects of non-odorant molecular vibrational modes. As a result, these and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.« less

Implausibility of the vibrational theory of olfaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Block, Eric; Ertem, Mehmed Z.; Jang, Seogjoo

The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. Here, we find no evidence for such differentiation at the molecular level. In fact, we find that the human musk-recognizing receptor, OR5AN1, identified using a heterologous OR expression system and robustly responding to cyclopentadecanone and muscone, fails to distinguish isotopomers of thesemore » compounds in vitro. Furthermore, the mouse (methylthio)methanethiol (MTMT)-recognizing receptor, MOR244-3, and other selected human and mouse ORs, responded similarly to normal, deuterated, and ¹³C isotopomers of their respective ligands, paralleling our results with the musk receptor OR5AN1. These findings suggest that the proposed vibration theory does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other ORs examined. Also, contrary to the vibration theory predictions, muscone-d₃₀ lacks the 1,380-1,550 cm⁻¹ IR bands claimed to be essential for musk odor. Furthermore, our theoretical analysis shows that the proposed electron transfer mechanism of the vibrational frequencies of odorants could be easily suppressed by quantum effects of non-odorant molecular vibrational modes. As a result, these and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.« less

Personal care products in wild fish in two main Chinese rivers: Bioaccumulation potential and human health risks.

PubMed

Yao, Li; Zhao, Jian-Liang; Liu, You-Sheng; Zhang, Qian-Qian; Jiang, Yu-Xia; Liu, Shan; Liu, Wang-Rong; Yang, Yuan-Yuan; Ying, Guang-Guo

2018-04-15

Personal care products (PCPs) are widely applied in our daily life, however, little is known about their occurrence in wild fish. We investigated the bioaccumulation and potential risks of 24 PCPs in muscle and liver tissues of wild fish collected from two large rivers of Pearl and Yangtze Rivers in China. The results showed the detection of a total of 13 PCPs including 9 biocides, 2 synthetic musks and 2 benzotriazoles in at least one type of fish tissue from 12 fish species. The compounds with high detection frequencies (>50%) in fish muscle or liver tissues were N,N-diethyl-3-methylbenzamide, carbendazim, climbazole, miconazole (MCZ), methylparaben, propylparaben, triclosan (TCS), tonalide, galaxolide (HHCB) and 5-methyl-1H-benzotriazole (5-TT). Among biocides, synthetic musks and benzotriazoles, TCS, HHCB and benzotriazole showed the maximum concentrations of 79.5ng/g wet weight (ww), 299ng/g ww and 3.14ng/g ww, respectively, in muscle tissue, while MCZ, HHCB and 5-TT showed the maximum concentrations of 432ng/g ww, 2619ng/g ww and 54.5ng/g ww, respectively, in liver tissue. The median values of logarithm of bioaccumulation factors (BAF) for the detected 13 PCPs were ranged 0.8-3.35 in muscle and 0.85-4.58 in liver. The log BAF values of the PCPs displayed good linear relationships with log K ow and log D ow (pH-dependent K ow ). The health hazard assessment of 10 detected PCPs in the muscle indicated no appreciable risk to human via consumption of the wild fish. Copyright © 2017 Elsevier B.V. All rights reserved.

Occurrence, distribution and bioaccumulation behaviour of hydrophobic organic contaminants in a large-scale constructed wetland in Singapore.

PubMed

Wang, Qian; Kelly, Barry C

2017-09-01

This study involved a field-based investigation to assess the occurrence, distribution and bioaccumulation behaviour of hydrophobic organic contaminants in a large-scale constructed wetland. Samples of raw leachate, water and wetland plants, Typha angustifolia, were collected for chemical analysis. Target contaminants included polychlorinated biphenyls (PCBs), organochlorine pesticides (OCP), as well as several halogenated flame retardants (HFRs) and personal care products (triclosan and synthetic musks). In addition to PCBs and OCPs, synthetic musks, triclosan (TCS) and dechlorane plus stereoisomers (syn- and anti-DPs) were frequently detected. Root concentration factors (log RCF L/kg wet weight) of the various contaminants ranged between 3.0 and 7.9. Leaf concentration factors (log LCF L/kg wet weight) ranged between 2.4 and 8.2. syn- and anti-DPs exhibited the greatest RCF and LCF values. A strong linear relationship was observed between log RCF and octanol-water partition coefficient (log K OW ). Translocation factors (log TFs) were negatively correlated with log K OW . The results demonstrate that more hydrophobic compounds exhibit higher degrees of partitioning into plant roots and are less effectively transported from roots to plant leaves. Methyl triclosan (MTCS) and 2,8-dichlorodibenzo-p-dioxin (DCDD), TCS degradation products, exhibited relatively high concentrations in roots and leaves., highlighting the importance of degradation/biotransformation. The results further suggest that Typha angustifolia in this constructed wetland can aid the removal of hydrophobic organic contaminants present in this landfill leachate. The findings will aid future investigations regarding the fate and bioaccumulation of hydrophobic organic contaminants in constructed wetlands. Copyright © 2017 Elsevier Ltd. All rights reserved.

Occurrence of Organic Wastewater Compounds in Selected Surface-Water Supplies, Triangle Area of North Carolina, 2002-2005

USGS Publications Warehouse

Giorgino, M.J.; Rasmussen, R.B.; Pfeifle, C.M .

2007-01-01

Selected organic wastewater compounds, such as household, industrial, and agricultural-use compounds, sterols, pharmaceuticals, and antibiotics, were measured at eight sites classified as drinking-water supplies in the Triangle Area of North Carolina. From October 2002 through July 2005, seven of the sites were sampled twice, and one site was sampled 28 times, for a total of 42 sets of environmental samples. Samples were analyzed for as many as 126 compounds using three laboratory analytical methods. These methods were developed by the U.S. Geological Survey to detect low levels (generally less than or equal to 1.0 microgram per liter) of the target compounds in filtered water. Because analyses were conducted on filtered samples, the results presented in this report may not reflect the total concentration of organic wastewater compounds in the waters that were sampled. Various quality-control samples were used to quality assure the results in terms of method performance and possible laboratory or field contamination. Of the 108 organic wastewater compounds that met method performance criteria, 24 were detected in at least one sample during the study. These 24 compounds included 3 pharmaceutical compounds, 6 fire retardants and plasticizers, 3 antibiotics, 3 pesticides, 6 fragrances and flavorants, 1 disinfectant, and 2 miscellaneous-use compounds, all of which likely originated from a variety of domestic, industrial, and agricultural sources. The 10 most frequently detected compounds included acetyl-hexamethyl tetrahydronaphthalene and hexahydro-hexamethyl cyclopentabenzopyran (synthetic musks that are widely used in personal-care products and are known endocrine disruptors); tri(2-chloroethyl) phosphate, tri(dichloroisopropyl) phosphate, and tributyl phosphate (fire retardants); metolachlor (herbicide); caffeine (nonprescription stimulant); cotinine (metabolite of nicotine); acetaminophen (nonprescription analgesic); and sulfamethoxazole (prescription antibiotic). The occurrence and distribution of organic wastewater compounds varied considerably among sampling sites, but at least one compound was detected at every location. The most organic wastewater compounds (19) were detected at the Neuse River above U.S. 70 at Smithfield, where two-thirds of the total number of samples were collected. The fewest organic wastewater compounds (1) were detected at the Eno River at Hillsborough. The detection of multiple organic wastewater compounds was common, with a median of 3.5 and as many as 12 compounds observed in individual samples. Some compounds, including acetaminophen, cotinine, tri(2-chloroethyl) phosphate, and metolachlor, were detected at numerous sites and in numerous samples, indicating that they are widely distributed in the environment. Other organic wastewater compounds, including acetyl-hexamethyl tetrahydronaphthalene and hexahydro-hexamethyl cyclopentabenzopyran, were detected in numerous samples but at only one location, indicating that sources of these compounds are more site specific. Results indicate that municipal wastewater may be a source of antibiotics and synthetic musks; however, the three sites in this study that are located downstream from wastewater discharges also receive runoff from agricultural, urban, and rural residential lands. Source identification was not an objective of this study. Concentrations of individual compounds generally were less than 0.5 microgram per liter. No concentrations exceeded Federal drinking-water standards or health advisories, nor water-quality criteria established by the State of North Carolina; however, such criteria are available for only a few of the compounds that were studied. Compared with other surface waters that have been sampled across the United States, the Triangle Area water-supply sites had fewer detections of organic wastewater compounds; however, differences in study design and analytical methods used among studies must be considered when mak

Behavior of the polycyclic musks HHCB and AHTN in lakes, two potential anthropogenic markers for domestic wastewater in surface waters.

PubMed

Buerge, Ignaz J; Buser, Hans-Rudolf; Müller, Markus D; Poiger, Thomas

2003-12-15

The synthetic polycyclic musks HHCB and AHTN are potential chemical markers for domestic wastewater contamination of surface waters. Understanding their environmental behavior is important to evaluate their suitability as markers. This study focuses on the quantification of the processes that lead to an elimination in lakes. Rate constants for all relevant processes were estimated based on laboratory studies and models previously described. In lake Zurich, during winter time, both compounds are eliminated primarily by outflowing water and due to losses to the atmosphere. In summer, direct photolysis represents the predominant elimination process for AHTN in the epilimnion of lake Zurich (quantum yield, 0.12), whereas for HHCB, photochemical degradation is still negligible. HHCB and AHTN were then measured in effluents of Swiss wastewater treatment plants (WWTPs), in remote and anthropogenically influenced Swiss surface waters, and in Mediterranean seawater using an analytical procedure based on SPE and GC-MS-SIM with D6-HHCB as internal standard (LODs for natural waters, 2 and 1 ng/L, respectively). In winter, concentrations of HHCB and AHTN in lakes (<2-47 and <1-18 ng/L, respectively) correlated with the anthropogenic burden by domestic wastewater (ratio population per water throughflow), demonstrating the suitability of these compounds as quantitative, source-specific markers. In summer, however, no such correlations were observed. Vertical concentration profiles in lake Zurich indicated significant losses in the epilimnion during summer, mainly for AHTN, and could be rationalized with a lake modeling program (MASASlight), considering measured, average loads from WWTP effluents (0.80 +/- 0.22 and 0.32 +/- 0.11 mg person(-1) d(-1) for HHCB and AHTN, respectively) and the estimated rate constants for elimination processes.

Transformation products and reaction kinetics of fragrances in advanced wastewater treatment with ozone.

PubMed

Janzen, Niklas; Dopp, Elke; Hesse, Julia; Richards, Jessica; Türk, Jochen; Bester, Kai

2011-11-01

The reaction of the fragrance compounds 4,6,6,7,8,8-hexamethyl-1,3,4,7-tetrahydrocyclopenta[g]isochromene (HHCB), 1-(3,5,5,6,8,8-hexamethyl-6,7-dihydronaphthalen-2-yl)ethanone (AHTN), 1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene (musk xylene/MX), 1-(4-tert-butyl-2,6-dimethyl-3,5-dinitrophenyl)ethanone (musk ketone/MK), and 1-(2,3,8,8-tetramethyl-1,3,4,5,6,7-hexahydronaphthalen-2-yl)ethanone (OTNE) with ozone in tap water as well as waste water treatment plant (WWTP) effluents is described. Several transformation products are characterized by means of gas chromatography coupled to mass spectrometry. One transformation product (HHCB-Lactone) was confirmed by means of a true standard. Musk xylene and musk ketone do not react with ozone under the conditions used in this study. AHTN and HHCB reacted slowly to a multitude of transformation products, while OTNE reacted quickly to several stable transformation products. The reaction constants and half lives are used to predict removal efficiencies for full scale reactors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Occurrence and toxicity of musks and UV filters in the marine environment.

PubMed

S, Rainieri; A, Barranco; M, Primec; T, Langerholc

2017-06-01

Emerging chemical contaminants in the marine ecosystem represent a threat to the environment and also to human health due to insufficient knowledge about their toxicity and bioaccumulation in the food chain. Consequently, many of them are not regulated. In this review we focus on musks and organic UV filters. For both groups of compounds we describe occurrence in the marine environment, toxic effects identified so far and methods used to identify such effects. The final objective of this work is to identify gaps in the understanding of their toxicology. Copyright © 2016 Elsevier Ltd. All rights reserved.

UV-filters and musk fragrances in seafood commercialized in Europe Union: Occurrence, risk and exposure assessment.

PubMed

Cunha, S C; Trabalón, L; Jacobs, S; Castro, M; Fernandez-Tejedor, M; Granby, K; Verbeke, W; Kwadijk, C; Ferrari, F; Robbens, J; Sioen, I; Pocurull, E; Marques, A; Fernandes, J O; Domingo, J L

2018-02-01

In the framework of the FP7 ECsafeSeafood project, 62 seafood samples commercialized in Europe Union from several representative species - mackerel, tuna, salmon, seabream, cod, monkfish, crab, shrimp, octopus, perch and plaice - were analysed for residues of 21 personal care products (PCPs), including 11 UV-filters (UV-Fs) and 10 musk fragrances (musks). PCPs analysis were performed by Quick, Easy, Cheap, Effective Rugged, Safe (QuEChERS), combined with liquid-liquid extraction (LLE) or dispersive solid-phase extraction (dSPE), followed by gas chromatography-tandem mass spectrometry (GC-MS/MS). The results showed the presence in a wide range of samples of nine out of eleven UV-Fs compounds analysed, namely 2-ethylhexyl salicylate (EHS), 2-ethylhexyl,4-methoxycinnamate (EHMC), 4-methylbenzylidenecamphor (4-MBC), benzophenone-1 (BP1), benzophenone-3 (BP3), isoamyl-4-methoxycinnamate (IMC), 2,2'-dihydroxy-4,4'-dimethoxybenzophenone (DHMB), homosalate (HS), and octocrylene (OC), whereas galaxolide (HHCB), galaxolide lactone (HHCB-lactone), and tonalide (AHTN) were the most found musks. The potential risks to human health associated with the exposure to eight of the more prevalent PCPs - EHS, EHMC, 4-MBC, BP1, BP3, IMC, HHCB, and AHTN - through seafood consumption were assessed for consumers from five European countries (Belgium, Ireland, Italy, Portugal and Spain). Results showed that the human exposure to UV-Fs and musks estimated from the concentration values found in seafood and the daily consumption of concerned seafood species, were far below toxicological reference values. Copyright © 2017 Elsevier Inc. All rights reserved.

Enantioselective Determination of Polycyclic Musks in River and Wastewater by GC/MS/MS

PubMed Central

Lee, Injung; Gopalan, Anantha-Iyengar; Lee, Kwang-Pill

2016-01-01

The separation of chiral compounds is an interesting and challenging topic in analytical chemistry, especially in environmental fields. Enantioselective degradation or bioaccumulation has been observed for several chiral pollutants. Polycyclic musks are chiral and are widely used as fragrances in a variety of personal care products such as soaps, shampoos, cosmetics and perfumes. In this study, the gas chromatographic separation of chiral polycyclic musks, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclo-penta-γ-2-benzopyrane (HHCB), 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetra-hydronaphthalene (AHTN), 6-acetyl-1,1,2,3,3,5-hexamethylindane (AHDI), 5-acetyl-1,1,2,6-tetramethyl-3-iso-propylindane (ATII), and 6,7-dihydro-1,1,2,3,3-pentamethyl-4(5H)-indanone (DPMI) was achieved on modified cyclodextrin stationary phase (heptakis (2,3-di-O-methyl-6-O-tert-butyl-dimethylsilyl-β-CD in DV-1701)). Separation techniques are coupled to tandem mass spectrometry (MS-MS), as it provides the sensitivity and selectivity needed. River and wastewaters (influents and effluents of wastewater treatment plants (WWTPs)) in the Nakdong River were investigated with regard to the concentrations and the enantiomeric ratios of polycyclic musks. HHCB was most frequently detected in river and wastewaters, and an enantiomeric enrichment was observed in the effluents of one of the investigated wastewater treatment plants (WWTPs). We reported the contamination of river and wastewaters in Korea by chiral polycyclic musks. The results of this investigation suggest that enantioselective transformation may occur during wastewater treatment. PMID:27011195

MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4

PubMed Central

Huijbers, Maartje G.; Zhang, Wei; Klooster, Rinse; Niks, Erik H.; Friese, Matthew B.; Straasheijm, Kirsten R.; Thijssen, Peter E.; Vrolijk, Hans; Plomp, Jaap J.; Vogels, Pauline; Losen, Mario; Van der Maarel, Silvère M.; Burden, Steven J.; Verschuuren, Jan J.

2013-01-01

Myasthenia gravis (MG) is a severely debilitating autoimmune disease that is due to a decrease in the efficiency of synaptic transmission at neuromuscular synapses. MG is caused by antibodies against postsynaptic proteins, including (i) acetylcholine receptors, the neurotransmitter receptor, (ii) muscle-specific kinase (MuSK), a receptor tyrosine kinase essential for the formation and maintenance of neuromuscular synapses, and (iii) low-density lipoprotein receptor-related protein 4 (Lrp4), which responds to neural Agrin by binding and stimulating MuSK. Passive transfer studies in mice have shown that IgG4 antibodies from MuSK MG patients cause disease without requiring complement or other immune components, suggesting that these MuSK antibodies cause disease by directly interfering with MuSK function. Here we show that pathogenic IgG4 antibodies to MuSK bind to a structural epitope in the first Ig-like domain of MuSK, prevent binding between MuSK and Lrp4, and inhibit Agrin-stimulated MuSK phosphorylation. In contrast, these IgG4 antibodies have no direct effect on MuSK dimerization or MuSK internalization. These results provide insight into the unique pathogenesis of MuSK MG and provide clues toward development of specific treatment options. PMID:24297891

Patient autoantibodies deplete postsynaptic muscle-specific kinase leading to disassembly of the ACh receptor scaffold and myasthenia gravis in mice

PubMed Central

Cole, R N; Ghazanfari, N; Ngo, S T; Gervásio, O L; Reddel, S W; Phillips, W D

2010-01-01

The postsynaptic muscle-specific kinase (MuSK) coordinates formation of the neuromuscular junction (NMJ) during embryonic development. Here we have studied the effects of MuSK autoantibodies upon the NMJ in adult mice. Daily injections of IgG from four MuSK autoantibody-positive myasthenia gravis patients (MuSK IgG; 45 mg day−1i.p. for 14 days) caused reductions in postsynaptic ACh receptor (AChR) packing as assessed by fluorescence resonance energy transfer (FRET). IgG from the patients with the highest titres of MuSK autoantibodies caused large (51–73%) reductions in postsynaptic MuSK staining (cf. control mice; P < 0.01) and muscle weakness. Among mice injected for 14 days with control and MuSK patient IgGs, the residual level of MuSK correlated with the degree of impairment of postsynaptic AChR packing. However, the loss of postsynaptic MuSK preceded this impairment of postsynaptic AChR. When added to cultured C2 muscle cells the MuSK autoantibodies caused tyrosine phosphorylation of MuSK and the AChR β-subunit, and internalization of MuSK from the plasma membrane. The results suggest a pathogenic mechanism in which MuSK autoantibodies rapidly deplete MuSK from the postsynaptic membrane leading to progressive dispersal of postsynaptic AChRs. Moreover, maintenance of postsynaptic AChR packing at the adult NMJ would appear to depend upon physical engagement of MuSK with the AChR scaffold, notwithstanding activation of the MuSK-rapsyn system of AChR clustering. PMID:20603331

Air-sea exchange fluxes of synthetic polycyclic musks in the North Sea and the Arctic.

PubMed

Xie, Zhiyong; Ebinghaus, Ralf; Temme, Christian; Heemken, Olaf; Ruck, Wolfgang

2007-08-15

Synthetic polycyclic musk fragrances Galaxolide (HHCB) and Tonalide (AHTN) were measured simultaneously in air and seawater in the Arctic and the North Sea and in the rural air of northern Germany. Median concentrations of gas-phase HHCB and AHTN were 4 and 18 pg m(-3) in the Arctic, 28 and 18 pg m(-3) in the North Sea, and 71 and 21 pg m(-3) in northern Germany, respectively. Various ratios of HHCB/AHTN implied that HHCB is quickly removed by atmospheric degradation, while AHTN is relatively persistent in the atmosphere. Dissolved concentrations ranged from 12 to 2030 pg L(-1) for HHCB and from below the method detection limit (3 pg L(-1)) to 965 pg L(-1) for AHTN with median values of 59 and 23 pg L(-1), respectively. The medians of volatilization fluxes for HHCB and AHTN were 27.2 and 14.2 ng m(-2) day(-1) and the depositional fluxes were 5.9 and 3.3 ng m(-2) day(-1), respectively, indicating water-to-air volatilization is a significant process to eliminate HHCB and AHTN from the North Sea. In the Arctic, deposition fluxes dominated the air-sea gas exchange of HHCB and AHTN, suggesting atmospheric input controls the levels of HHCB and AHTN in the polar region.

Effect of cannabinoids on lithium-induced vomiting in the Suncus murinus (house musk shrew).

PubMed

Parker, Linda A; Kwiatkowska, Magdalena; Burton, Page; Mechoulam, Raphael

2004-01-01

Marijuana has been reported to interfere with nausea and vomiting in chemotherapy patients. The principal cannabinoids found in marijuana include the psychoactive compound Delta-9-tetrahydrocannabinol (THC) and the non-psychoactive compound cannabidiol (CBD). The experiments reported here evaluated the potential of THC and CBD to interfere with vomiting in the Suncus murinus (house musk shrew) produced by lithium chloride (LiCl), which is the most commonly employed unconditioned stimulus for taste avoidance. To evaluate the potential of the principal components of marijuana, THC and CBD, to suppress Li-induced vomiting in the house musk shrew. Shrews were injected with vehicle or one of two cannabinoids [Delta-9-THC (1-20 mg/kg), or CBD (2.5-40 mg/kg)] 10 min prior to an injection of LiCl (390 mg/kg of 0.15 M) and were then observed for 45 min. The frequency of vomiting episodes and the latency to the first episode were measured. The role of the CB1 receptor in these effects was also evaluated by pretreatment with SR-141716. Delta-9-THC produced a dose-dependent suppression of Li-induced vomiting, with higher doses producing greater suppression than lower doses. CBD produced a biphasic effect with lower doses producing suppression and higher doses producing enhancement of Li-induced vomiting. The suppression of Li-induced vomiting by THC, but not by CBD, was reversed by SR-141716. These results indicate that two major cannabinoid compounds found in marijuana, THC and CBD, are effective treatments for Li-induced vomiting; however, only THC acts by the CB1 receptor. The effects of THC and CBD on vomiting were dose dependent; with THC the effect was linear, but with CBD the effect was biphasic.

Evaluation of a Screening System for Obesogenic Compounds: Screening of Endocrine Disrupting Compounds and Evaluation of the PPAR Dependency of the Effect

PubMed Central

Pereira-Fernandes, Anna; Demaegdt, Heidi; Vandermeiren, Karine; Hectors, Tine L. M.; Jorens, Philippe G.; Blust, Ronny; Vanparys, Caroline

2013-01-01

Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs) in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol for obesogen screening based on the 3T3-L1 cell line, a well-characterised adipogenesis model, and direct fluorescent measurement using Nile red lipid staining technique. In a first phase, we characterised the assay using the acknowledged obesogens rosiglitazone and tributyltin. Based on the obtained dose-response curves for these model compounds, a lipid accumulation threshold value was calculated to ensure the biological relevance and reliability of statistically significant effects. This threshold based method was combined with the well described strictly standardized mean difference (SSMD) method for classification of non-, weak- or strong obesogenic compounds. In the next step, a range of EDCs, used in personal and household care products (parabens, musks, phthalates and alkylphenol compounds), were tested to further evaluate the obesogenicity screening assay for its discriminative power and sensitivity. Additionally, the peroxisome proliferator activated receptor γ (PPARγ) dependency of the positive compounds was evaluated using PPARγ activation and antagonist experiments. Our results showed the adipogenic potential of all tested parabens, several musks and phthalate compounds and bisphenol A (BPA). PPARγ activation was associated with adipogenesis for parabens, phthalates and BPA, however not required for obesogenic effects induced by Tonalide, indicating the role of other obesogenic mechanisms for this compound. PMID:24155963

[Research progress on molecular genetics of forest musk deer].

PubMed

Jie, Hang; Zheng, Cheng-li; Wang, Jian-ming; Feng, Xiao-lan; Zeng, De-jun; Zhao, Gui-jun

2015-11-01

Forest musk deer is one of the large-scale farming musk deer animals with the largest population at the same time. The male musk deer can secrete valuable medicines, which has high medicinal and economic value. Due to the loss of habitat and indiscriminate hunting, the numbers of wild population specie and the distribution have been drastically reduced. Therefore, in-depth understanding of the molecular genetics progress of forest musk deer will pave a way for musk deer protection and breeding. In this review, the progress associated with the molecular marker, genetic classification, artificial breeding, musk secretion and disease in past decades were reviewed, in order to provide a theoretical basis for subsequent molecular genetic researches in forest musk deer.

Patch-clamp analysis of voltage-activated and chemically activated currents in the vomeronasal organ of Sternotherus odoratus (stinkpot/musk turtle)

PubMed Central

Fadool, D. A.; Wachowiak, M.; Brann, J. H.

2011-01-01

Summary The electrophysiological basis of chemical communication in the specialized olfactory division of the vomeronasal (VN) organ is poorly understood. In total, 198 patch-clamp recordings were made from 42 animals (Sternotherus odoratus, the stinkpot/musk turtle) to study the electrically and chemically activated properties of VN neurons. The introduction of tetramethylrhodamine-conjugated dextran into the VN orifice permitted good visualization of the vomeronasal neural epithelium prior to dissociating it into single neurons. Basic electrical properties of the neurons were measured (resting potential, −54.5±2.7 mV, N=11; input resistance, 6.7±1.4GΩ, N=25; capacitance, 4.2±0.3 pF, N=22; means ± S.E.M.). The voltage-gated K+ current inactivation rate was significantly slower in VN neurons from males than in those from females, and K+ currents in males were less sensitive (greater Ki) to tetraethylammonium. Vomeronasal neurons were held at a holding potential of −60 mV and tested for their response to five natural chemicals, female urine, male urine, female musk, male musk and catfish extract. Of the 90 VN neurons tested, 33 (34 %) responded to at least one of the five compounds. The peak amplitude of chemically evoked currents ranged from 4 to 180 pA, with two-thirds of responses less than 25 pA. Urine-evoked currents were of either polarity, whereas musk and catfish extract always elicited only inward currents. Urine applied to neurons harvested from female animals evoked currents that were 2–3 times larger than those elicited from male neurons. Musk-evoked inward currents were three times the magnitude of urine-or catfish-extract-evoked inward currents. The calculated breadth of responsiveness for neurons presented with this array of five chemicals indicated that the mean response spectrum of the VN neurons is narrow (H metric 0.11). This patch-clamp study indicates that VN neurons exhibit sexual dimorphism in function and specificity in response to complex natural chemicals. PMID:11815645

Patch-clamp analysis of voltage-activated and chemically activated currents in the vomeronasal organ of Sternotherus odoratus (stinkpot/musk turtle).

PubMed

Fadool, D A; Wachowiak, M; Brann, J H

2001-12-01

The electrophysiological basis of chemical communication in the specialized olfactory division of the vomeronasal (VN) organ is poorly understood. In total, 198 patch-clamp recordings were made from 42 animals (Sternotherus odoratus, the stinkpot/musk turtle) to study the electrically and chemically activated properties of VN neurons. The introduction of tetramethylrhodamine-conjugated dextran into the VN orifice permitted good visualization of the vomeronasal neural epithelium prior to dissociating it into single neurons. Basic electrical properties of the neurons were measured (resting potential, -54.5 +/- 2.7 mV, N=11; input resistance, 6.7 +/- 1.4 G Omega, N=25; capacitance, 4.2 +/- 0.3 pF, N=22; means +/- S.E.M.). The voltage-gated K(+) current inactivation rate was significantly slower in VN neurons from males than in those from females, and K(+) currents in males were less sensitive (greater K(i)) to tetraethylammonium. Vomeronasal neurons were held at a holding potential of -60 mV and tested for their response to five natural chemicals, female urine, male urine, female musk, male musk and catfish extract. Of the 90 VN neurons tested, 33 (34 %) responded to at least one of the five compounds. The peak amplitude of chemically evoked currents ranged from 4 to 180 pA, with two-thirds of responses less than 25 pA. Urine-evoked currents were of either polarity, whereas musk and catfish extract always elicited only inward currents. Urine applied to neurons harvested from female animals evoked currents that were 2-3 times larger than those elicited from male neurons. Musk-evoked inward currents were three times the magnitude of urine- or catfish-extract-evoked inward currents. The calculated breadth of responsiveness for neurons presented with this array of five chemicals indicated that the mean response spectrum of the VN neurons is narrow (H metric 0.11). This patch-clamp study indicates that VN neurons exhibit sexual dimorphism in function and specificity in response to complex natural chemicals.iol

The draft genome sequence of forest musk deer (Moschus berezovskii).

PubMed

Fan, Zhenxin; Li, Wujiao; Jin, Jiazheng; Cui, Kai; Yan, Chaochao; Peng, Changjun; Jian, Zuoyi; Bu, Ping; Price, Megan; Zhang, Xiuyue; Shen, Yongmei; Li, Jing; Q, Wenhua; Yue, Bisong

2018-04-01

The forest musk deer, Moschus berezovskii, is one of seven musk deer (Moschus spp.) and is distributed in Southwest China. Akin to other musk deer, the forest musk deer has been traditionally and is currently hunted for its musk (i.e., global perfume industry). Considerable hunting pressure and habitat loss have caused significant population declines. Consequently, the Chinese government commenced captive breeding programs for musk harvesting in the 1950s. However, the prevalence of fatal diseases is considerably restricting population increases. Disease severity and extent are exacerbated by inbreeding and genetic diversity declines in captive musk deer populations. It is essential that knowledge of captive and wild forest musk deer populations' immune system and genome be gained in order to improve their physical and genetic health. We have thus sequenced the whole genome of the forest musk deer, completed the genomic assembly and annotation, and performed preliminary bioinformatic analyses. A total of 407 Gb raw reads from whole-genome sequencing were generated using the Illumina HiSeq 4000 platform. The final genome assembly is around 2.72 Gb, with a contig N50 length of 22.6 kb and a scaffold N50 length of 2.85 Mb. We identified 24,352 genes and found that 42.05% of the genome is composed of repetitive elements. We also detected 1,236 olfactory receptor genes. The genome-wide phylogenetic tree indicated that the forest musk deer was within the order Artiodactyla, and it appeared as the sister clade of four members of Bovidae. In total, 576 genes were under positive selection in the forest musk deer lineage. We provide the first genome sequence and gene annotation for the forest musk deer. The availability of these resources will be very useful for the conservation and captive breeding of this endangered and economically important species and for reconstructing the evolutionary history of the order Artiodactyla.

Advertising displays of male Musk Ducks indicate population subdivision across the Nullarbor Plain of Australia

USGS Publications Warehouse

McCracken, K.G.; Fullagar, P.J.; Slater, E.C.; Paton, D.C.; Afton, A.D.

2002-01-01

Acoustic advertising displays (n=75) of male Musk Ducks Biziura lobata were analysed at ten widely spaced geographic localities in South Australia, Victoria, and Western Australia. Vocalisations differed in a fixed, non-overlapping pattern between allopatric Musk Duck populations in southeastern and southwestern Australia. These findings suggest that Musk Duck populations are subdivided by the Nullarbor Plain, the arid treeless desert at the head of the Great Australian Bight. Three vocalisations performed by male Musk Ducks not previously reported in the literature were documented also. Vocalisations of captive Musk Ducks collected from different geographic regions (southeast and southwest) differed between regions from which captives originally were collected and were unlike those performed by wild birds. Based on calls of immature Musk Ducks, acoustic variation within regional populations and the apparent inability of captive Musk Ducks reared in isolation to develop the wild type adult call, regional dialects seemingly are acquired in a social context by repeated observance of adult males and some combination of social imprinting, learning, or practice.

Diverging roles for Lrp4 and Wnt signaling in neuromuscular synapse development during evolution.

PubMed

Remédio, Leonor; Gribble, Katherine D; Lee, Jennifer K; Kim, Natalie; Hallock, Peter T; Delestrée, Nicolas; Mentis, George Z; Froemke, Robert C; Granato, Michael; Burden, Steven J

2016-05-01

Motor axons approach muscles that are prepatterned in the prospective synaptic region. In mice, prepatterning of acetylcholine receptors requires Lrp4, a LDLR family member, and MuSK, a receptor tyrosine kinase. Lrp4 can bind and stimulate MuSK, strongly suggesting that association between Lrp4 and MuSK, independent of additional ligands, initiates prepatterning in mice. In zebrafish, Wnts, which bind the Frizzled (Fz)-like domain in MuSK, are required for prepatterning, suggesting that Wnts may contribute to prepatterning and neuromuscular development in mammals. We show that prepatterning in mice requires Lrp4 but not the MuSK Fz-like domain. In contrast, prepatterning in zebrafish requires the MuSK Fz-like domain but not Lrp4. Despite these differences, neuromuscular synapse formation in zebrafish and mice share similar mechanisms, requiring Lrp4, MuSK, and neuronal Agrin but not the MuSK Fz-like domain or Wnt production from muscle. Our findings demonstrate that evolutionary divergent mechanisms establish muscle prepatterning in zebrafish and mice. © 2016 Remédio et al.; Published by Cold Spring Harbor Laboratory Press.

Leading in the Arctic; Translating the United States Arctic Strategy into Opportunities for Peace and Stability

DTIC Science & Technology

2015-02-16

Elon Musk , the well-known founder of Tesla and Space-X. His life’s work focuses on developing the means to find and get to...nat_arctic_strategy.pdf 58. Elon Musk , “ Elon Musk -The man behind Tesla, Space X, Solar City…” (Filmed February 2013, TED video, 21:04. Posted March 2013) https...Exploitation. London, UK: Reaktion Books Ltd., 2012. Musk , Elon . “ Elon Musk -The man behind Tesla, Space X, Solar City…” Filmed February 2013, TED

Environmentally relevant concentrations of galaxolide (HHCB) and tonalide (AHTN) induced oxidative and genetic damage in Dreissena polymorpha.

PubMed

Parolini, Marco; Magni, Stefano; Traversi, Irene; Villa, Sara; Finizio, Antonio; Binelli, Andrea

2015-03-21

Synthetic musk compounds (SMCs) are extensively used as fragrances in several personal care products and have been recognized as emerging aquatic pollutants. Among SMCs, galaxolide (HHCB) and tonalide (AHTN) are extensively used and have been measured in aquatic ecosystems worldwide. However, their potential risk to organisms remains largely unknown. The aim of this study was to investigate whether 21-day exposures to HHCB and AHTN concentrations frequently measured in aquatic ecosystems can induce oxidative and genetic damage in Dreissena polymorpha. The lipid peroxidation (LPO) and protein carbonyl content (PCC) were measured as oxidative stress indexes, while the DNA precipitation assay and the micronucleus test (MN test) were applied to investigate genetic injuries. HHCB induced significant increases in LPO and PCC levels, while AHTN enhanced only protein carbonylation. Moreover, significant increases in DNA strand breaks were caused by exposure to the highest concentrations of HHCB and AHTN tested in the present study, but no fixed genetic damage was observed. Copyright © 2014 Elsevier B.V. All rights reserved.

Traditional Chinese medicine and sports drug testing: identification of natural steroid administration in doping control urine samples resulting from musk (pod) extracts.

PubMed

Thevis, Mario; Schänzer, Wilhelm; Geyer, Hans; Thieme, Detlef; Grosse, Joachim; Rautenberg, Claudia; Flenker, Ulrich; Beuck, Simon; Thomas, Andreas; Holland, Ruben; Dvorak, Jiri

2013-01-01

The administration of musk extract, that is, ingredients obtained by extraction of the liquid secreted from the preputial gland or resulting grains of the male musk deer (eg, Moschus moschiferus), has been recommended in Traditional Chinese Medicine (TCM) applications and was listed in the Japanese pharmacopoeia for various indications requiring cardiovascular stimulation, anti-inflammatory medication or androgenic hormone therapy. Numerous steroidal components including cholesterol, 5α-androstane-3,17-dione, 5β-androstane-3,17-dione, androsterone, etiocholanolone, epiandrosterone, 3β-hydroxy-androst-5-en-17-one, androst-4-ene-3,17-dione and the corresponding urea adduct 3α-ureido-androst-4-en-17-one were characterised as natural ingredients of musk over several decades, implicating an issue concerning doping controls if used for the treatment of elite athletes. In the present study, the impact of musk extract administration on sports drug testing results of five females competing in an international sporting event is reported. In the course of routine doping controls, adverse analytical findings concerning the athletes' steroid profile, corroborated by isotope-ratio mass spectrometry (IRMS) data, were obtained. The athletes' medical advisors admitted the prescription of TCM-based musk pod preparations and provided musk pod samples for comparison purposes to clarify the antidoping rule violation. Steroid profiles, IRMS results, literature data and a musk sample obtained from a living musk deer of a local zoo conclusively demonstrated the use of musk pod extracts in all cases which, however, represented a doping offence as prohibited anabolic-androgenic steroids were administered.

Muscle-specific kinase (MuSK) autoantibodies suppress the MuSK pathway and ACh receptor retention at the mouse neuromuscular junction

PubMed Central

Ghazanfari, Nazanin; Morsch, Marco; Reddel, Stephen W; Liang, Simon X; Phillips, William D

2014-01-01

Muscle-specific kinase (MuSK) autoantibodies from myasthenia gravis patients can block the activation of MuSK in vitro and/or reduce the postsynaptic localization of MuSK. Here we use a mouse model to examine the effects of MuSK autoantibodies upon some key components of the postsynaptic MuSK pathway and upon the regulation of junctional ACh receptor (AChR) numbers. Mice became weak after 14 daily injections of anti-MuSK-positive patient IgG. The intensity and area of AChR staining at the motor endplate was markedly reduced. Pulse-labelling of AChRs revealed an accelerated loss of pre-existing AChRs from postsynaptic AChR clusters without a compensatory increase in incorporation of (newly synthesized) replacement AChRs. Large, postsynaptic AChR clusters were replaced by a constellation of tiny AChR microaggregates. Puncta of AChR staining also appeared in the cytoplasm beneath the endplate. Endplate staining for MuSK, activated Src, rapsyn and AChR were all reduced in intensity. In the tibialis anterior muscle there was also evidence that phosphorylation of the AChR β-subunit-Y390 was reduced at endplates. In contrast, endplate staining for β-dystroglycan (through which rapsyn couples AChR to the synaptic basement membrane) remained intense. The results suggest that anti-MuSK IgG suppresses the endplate density of MuSK, thereby down-regulating MuSK signalling activity and the retention of junctional AChRs locally within the postsynaptic membrane scaffold. PMID:24860174

Crystal Structure of the Agrin-Responsive Immunoglobulin-like Domains 1 and 2 of the Receptor Tyrosine Kinase MuSK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stiegler,A.; Burden, S.; Hubbard, S.

Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed exclusively in skeletal muscle, where it is required for formation of the neuromuscular junction. MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. Here, we report the crystal structure of the agrin-responsive first and second immunoglobulin-like domains (Ig1 and Ig2) of the MuSK ectodomain at 2.2 {angstrom} resolution. The structure reveals that MuSK Ig1 and Ig2 are Ig-like domains of the I-set subfamily, which are configured in a linear, semi-rigid arrangement. In addition to the canonical internal disulfide bridge, Ig1 contains a second, solvent-exposed disulfide bridge, which our biochemical datamore » indicate is critical for proper folding of Ig1 and processing of MuSK. Two Ig1-2 molecules form a non-crystallographic dimer that is mediated by a unique hydrophobic patch on the surface of Ig1. Biochemical analyses of MuSK mutants introduced into MuSK{sup -/-} myotubes demonstrate that residues in this hydrophobic patch are critical for agrin-induced MuSK activation.« less

Occurrence and Fate of Trace Contaminants during Aerobic and Anaerobic Sludge Digestion and Dewatering.

PubMed

Guerra, Paula; Kleywegt, Sonya; Payne, Michael; Svoboda, M Lewina; Lee, Hing-Biu; Reiner, Eric; Kolic, Terry; Metcalfe, Chris; Smyth, Shirley Anne

2015-07-01

Digestion of municipal wastewater biosolids is a necessary prerequisite to their beneficial use in land application, in order to protect public health and the receiving environment. In this study, 13 pharmaceuticals and personal care products (PPCPs), 11 musks, and 17 polybrominated diphenyl ethers were analyzed in 84 samples including primary sludge, waste activated sludge, digested biosolids, dewatered biosolids, and dewatering centrate or filtrate collected from five wastewater treatment plants with aerobic or anaerobic digestion. Aerobic digestion processes were sampled during both warm and cold temperatures to analyze seasonal differences. Among the studied compounds, triclosan, triclocarban, galaxolide, and BDE-209 were the substances most frequently detected under different treatment processes at levels up to 30,000 ng/g dry weight. Comparing aerobic and anaerobic digestion, it was observed that the levels of certain PPCPs and musks were significantly higher in anaerobically digested biosolids, relative to the residues from aerobic digestion. Therefore, aerobic digestion has the potential advantage of reducing levels of PPCPs and musks. On the other hand, anaerobic digestion has the advantage of recovering energy from the biosolids in the form of combustible gases while retaining the nutrient and soil conditioning value of this resource. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Characterization of CD4 and CD8 T Cell Responses in MuSK Myasthenia Gravis

PubMed Central

Yi, JS; Guidon, A; Sparks, S; Osborne, R; Juel, VC; Massey, JM; Sanders, DB; Weinhold, KJ; Guptill, JT

2014-01-01

Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T-cell responses in patients with MuSK MG. Intracellular production of IFN-gamma, TNF-alpha, IL-2, IL-17, and IL-21 by CD4+ and CD8+ T-cells was measured by polychromatic flow cytometry in peripheral blood samples from 11 Musk MG patients and 10 healthy controls. Only one MuSK MG patient was not receiving immunosuppressive therapy. Regulatory T-cells (Treg) were also included in our analysis to determine if changes in T cell function were due to altered Treg frequencies. CD8+ T-cells from MuSK MG patients had higher frequencies of polyfunctional responses than controls, and CD4+ T-cells had higher IL-2, TNF-alpha, and IL-17. MuSK MG patients had a higher percentage of CD4+ T-cells producing combinations of IFN-gamma/IL-2/TNF-gamma, TNF-alpha/IL-2, and IFN-gamma/TNF-alpha. Interestingly, Treg numbers and CD39 expression were not different from control values. MuSK MG patients had increased frequencies of Th1 and Th17 cytokines and were primed for polyfunctional proinflammatory responses that cannot be explained by a defect in Treg function or number. PMID:24378287

Muscle-specific kinase (MuSK) autoantibodies suppress the MuSK pathway and ACh receptor retention at the mouse neuromuscular junction.

PubMed

Ghazanfari, Nazanin; Morsch, Marco; Reddel, Stephen W; Liang, Simon X; Phillips, William D

2014-07-01

Muscle-specific kinase (MuSK) autoantibodies from myasthenia gravis patients can block the activation of MuSK in vitro and/or reduce the postsynaptic localization of MuSK. Here we use a mouse model to examine the effects of MuSK autoantibodies upon some key components of the postsynaptic MuSK pathway and upon the regulation of junctional ACh receptor (AChR) numbers. Mice became weak after 14 daily injections of anti-MuSK-positive patient IgG. The intensity and area of AChR staining at the motor endplate was markedly reduced. Pulse-labelling of AChRs revealed an accelerated loss of pre-existing AChRs from postsynaptic AChR clusters without a compensatory increase in incorporation of (newly synthesized) replacement AChRs. Large, postsynaptic AChR clusters were replaced by a constellation of tiny AChR microaggregates. Puncta of AChR staining also appeared in the cytoplasm beneath the endplate. Endplate staining for MuSK, activated Src, rapsyn and AChR were all reduced in intensity. In the tibialis anterior muscle there was also evidence that phosphorylation of the AChR β-subunit-Y390 was reduced at endplates. In contrast, endplate staining for β-dystroglycan (through which rapsyn couples AChR to the synaptic basement membrane) remained intense. The results suggest that anti-MuSK IgG suppresses the endplate density of MuSK, thereby down-regulating MuSK signalling activity and the retention of junctional AChRs locally within the postsynaptic membrane scaffold. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Can odors of TCM be captured by electronic nose? The novel quality control method for musk by electronic nose coupled with chemometrics.

PubMed

Ye, Tao; Jin, Cheng; Zhou, Jian; Li, Xingfeng; Wang, Haitao; Deng, Pingye; Yang, Ying; Wu, Yanwen; Xiao, Xiaohe

2011-07-15

Musk is a precious and wide applied material in traditional Chinese medicine, also, an important material for the perfume industry all over the world. To establish a rapid, cost-effective and relatively objective assessment for the quality of musk, different musk samples, including authentic, fake and adulterate, were collected. A oxide sensor based electronic nose (E-nose) was employed to measure the musk samples, the E-nose generated data were analyzed by principal component analysis (PCA), the responses of 18 sensors of E-nose were evaluated by loading analysis. Results showed that a rapid evaluation of complex response of the samples could be obtained, in combination with PCA and the perception level of the E-nose was given better results in the recognition values of the musk aroma. The authentic, fake and adulterate musk could be distinguished by E-nose coupled with PCA, sensor 2, 3, 5, 12, 15 and 17 were found to be able to better discriminate between musk samples, confirming the potential application of an electronic instrument coupled with chemometrics for a rapid and on-line quality control for the traditional medicines. Copyright © 2011 Elsevier B.V. All rights reserved.

The Role of Musk in Relieving the Neurodegenerative Changes Induced After Exposure to Chronic Stress.

PubMed

Abd El Wahab, Manal Galal; Ali, Soad Shaker; Ayuob, Nasra Naeim

2018-06-01

This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined. Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine. Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

Comparison Between the Fecal Bacterial Microbiota of Healthy and Diarrheic Captive Musk Deer

PubMed Central

Li, Yimeng; Hu, Xiaolong; Yang, Shuang; Zhou, Juntong; Qi, Lei; Sun, Xiaoning; Fan, Mengyuan; Xu, Shanghua; Cha, Muha; Zhang, Meishan; Lin, Shaobi; Liu, Shuqiang; Hu, Defu

2018-01-01

Diarrhea constitutes one of the most common diseases affecting the survival of captive musk deer and is usually caused by an imbalance in intestinal microbiota. Currently, research regarding the structure and function of intestinal microbiota in diarrheic musk deer is lacking. Therefore, in the present study, high-throughput 16S-rRNA gene sequencing was used to analyze the intestinal microbiota in feces of healthy captive musk deer (HMD) (n = 8) and musk deer with mild (MMD) (n = 8), and severe (n = 5) (SMD) diarrhea to compare the difference in intestinal microbiota of musk deer under various physiological conditions. The results showed that the diversity of HMD fecal microbiota was significantly higher than that of the two diarrhea samples. β Diversity results indicated that there were extremely significant differences in bacterial communities between the HMD sample and the MMD and SMD samples. However, no significant difference was found between the two diarrhea samples. LefSe analysis showed that the degree of intestinal physiological dysfunction in musk deer was correlated with the types of major pathogens. The main pathogen in the MMD group is Escherichia–Shigella, whereas Fusobacterium is the main pathogen in the SMD group. PICRUSt functional profile prediction indicated that the intestinal microbiota disorder could also lead to changes in the abundance of genes in metabolic pathways of the immune system. Altogether, this study provides a theoretical basis for the exploration of treatments for diarrhea in captive musk deer, which is of considerable significance to the implementation of the musk deer release into the wild program. PMID:29551996

Fragrance compounds: The wolves in sheep's clothings.

PubMed

Patel, Seema

2017-05-01

In the past few decades, synthetic fragrance compounds have become ubiquitous components of personal care and household cleaning products. Overwhelming consumerism trends have led to the excess usage of these chemicals. It has been observed that this fragrance-laden unhealthy lifestyle runs parallel with the unprecedented rates of diabetes, cancer, neural ailments, teratogenicity, and transgender instances. The link between fragrances as and the multiplicity of pathogens remained latent for decades. However, now this health hazard and its role in homeostasis breakdown is getting attention. The adverse effects of the fragrance constituents as phthalates, paraben, glutaraldehyde, hydroperoxides, oil of turpentine, metals, nitro musks, and essential oils, among others, are being identified. The endocrine-immune-neural axis perturbation pathways of these chemicals are being proven. Despite the revelations of cause-effect nexus, a majority of the vulnerable populations are unaware and unmotivated to avoid these 'slow poisons'. Hence, the researchers need to further validate the toxicity of fragrance compounds, and raise awareness towards the health risks. In this regard, a number of pathologies triggered by fragrance exposure, yet proven only scantily have been hypothesized. Analysis of the health issues from multiple facets, including the pivotal 'stressors - extracellular acidosis - aromatase upregulation - estrogen hyperproduction - inflammation' link has been proposed. Fragrance compounds share configurational similarity with carcinogenic environmental hydrocarbons and they provoke the expression of cytochrome group monooxygenase enzyme aromatase. This enzyme aromatizes androgens to form estrogen, the powerful signaling hormone, which underlies the majority of morbidities. This holistic review with a repertoire of preliminary evidences and robust hypotheses is expected to usher in deserving extent of research on this pervasive health risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

Crystal Structure of the Frizzled-Like Cysteine-Rich Domain of the Receptor Tyrosine Kinase MuSK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stiegler, A.; Burden, S; Hubbard, S

Muscle-specific kinase (MuSK) is an essential receptor tyrosine kinase for the establishment and maintenance of the neuromuscular junction (NMJ). Activation of MuSK by agrin, a neuronally derived heparan-sulfate proteoglycan, and LRP4 (low-density lipoprotein receptor-related protein-4), the agrin receptor, leads to clustering of acetylcholine receptors on the postsynaptic side of the NMJ. The ectodomain of MuSK comprises three immunoglobulin-like domains and a cysteine-rich domain (Fz-CRD) related to those in Frizzled proteins, the receptors for Wnts. Here, we report the crystal structure of the MuSK Fz-CRD at 2.1 {angstrom} resolution. The structure reveals a five-disulfide-bridged domain similar to CRDs of Frizzled proteinsmore » but with a divergent C-terminal region. An asymmetric dimer present in the crystal structure implicates surface hydrophobic residues that may function in homotypic or heterotypic interactions to mediate co-clustering of MuSK, rapsyn, and acetylcholine receptors at the NMJ.« less

Applicability of polydimethylsiloxane (PDMS) and polyethersulfone (PES) as passive samplers of more hydrophobic organic compounds in intertidal estuarine environments.

PubMed

Posada-Ureta, Oscar; Olivares, Maitane; Delgado, Alejandra; Prieto, Ailette; Vallejo, Asier; Irazola, Mireia; Paschke, Albrecht; Etxebarria, Nestor

2017-02-01

The uptake calibration of three passive samplers, stir-bars, MESCO/stir-bars and polyethersulfone tubes (PES t ), was assessed in seawater at different salinities for 17 organic compounds including organochlorine compounds, pesticides, phthalates, musk fragrances and triclosan. The calibration procedure was accomplished by exposing the samplers to a continuous flow of fortified seawater for up to 14days under laboratory conditions. Prior to the exposure, stir-bars and MESCO/stir-bars were loaded with a known amount of deuterated PAH mixture as performance reference compounds (PRC). For most of the studied compounds, the sampling rates (Rs, mL·day -1 ) were determined for each sampler at two salinities (15 and 30‰) and two nominal concentrations (25 and 50ng·L -1 ). Among the tested devices, though PES can be an outstanding cheap alternative to other passive samplers, naked or free stir-bars provided the best results in terms of uptake rates (i.e., the Rs values ranged from 30 to 350mL·day -1 ). Regarding the variation of the salinity, the Rs values obtained with naked stir-bars were statistically comparable in the full range of salinities (0-30‰) but the values obtained with MESCO/stir-bars and PES t were salinity dependent. Consequently, only stir-bars assured the required robustness to be used as passive samplers in intertidal estuarine environments. Finally, the stir-bars were applied to estimate the time-weighted average concentration of some of those contaminants in the feeding seawater of the experimental aquaria at the Plentzia Marine Station (Basque Country) and low levels of musks fragrances (0.1-0.2ng·L -1 ) were estimated. Copyright © 2016 Elsevier B.V. All rights reserved.

Semi-volatile organic compounds in the particulate phase in dwellings: A nationwide survey in France

NASA Astrophysics Data System (ADS)

Mandin, Corinne; Mercier, Fabien; Ramalho, Olivier; Lucas, Jean-Paul; Gilles, Erwann; Blanchard, Olivier; Bonvallot, Nathalie; Glorennec, Philippe; Le Bot, Barbara

2016-07-01

Sixty-six semi-volatile organic compounds (SVOCs)-phthalates, polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), one pyrethroid, organochlorine and organophosphorous pesticides, alkylphenols, synthetic musks, tri-n-butylphosphate and triclosan-were measured on PM10 filters collected over 7 days during a nationwide survey of 285 French dwellings, representative of nearly 25 million housing units. Thirty-five compounds were detected in more than half of the dwellings. PAHs, phthalates and triclosan were the major particle-bound SVOCs, with a median concentration greater than 1 ng m-3 for butylbenzyl phthalate (BBP) (median: 1.6 ng m-3), di(2-ethylhexyl) phthalate (DEHP) (46 ng m-3) and di-iso-nonyl phthalate (DiNP) (7.9 ng m-3), and greater than 0.1 ng m-3 for triclosan (114 pg m-3), benzo(a)pyrene (138 pg m-3), benzo(b)fluoranthene (306 pg m-3), benzo(g,h,i)perylene (229 pg m-3), and indeno(1,2,3-c,d)pyrene (178 pg m-3). For most of the SVOCs, higher concentrations were found in the dwellings of smokers and during the heating season. The concentrations of banned SVOCs-namely, PCBs and organochlorine pesticides-were correlated. Permethrin, 4-tert-butylphenol and bisphenol-A showed no correlation with the other SVOCs and seemed to have their own specific sources. Most SVOCs were positively associated with PM10 concentration, suggesting that any factor that raises the mass of indoor airborne particles also increases the exposure to SVOCs through inhalation.

Identifying Chemical Groups for Biomonitoring

PubMed Central

Krowech, Gail; Hoover, Sara; Plummer, Laurel; Sandy, Martha; Zeise, Lauren; Solomon, Gina

2016-01-01

Summary: Regulatory agencies face daunting challenges identifying emerging chemical hazards because of the large number of chemicals in commerce and limited data on exposure and toxicology. Evaluating one chemical at a time is inefficient and can lead to replacement with uncharacterized chemicals or chemicals with structural features already linked to toxicity. The Office of Environmental Health Hazard Assessment (OEHHA) has developed a process for constructing and assessing chemical groups for potential biomonitoring in California. We screen for chemicals with significant exposure potential and propose possible chemical groups, based on structure and function. To support formal consideration of these groups by Biomonitoring California’s Scientific Guidance Panel, we conduct a detailed review of exposure and toxicity data and examine the likelihood of detection in biological samples. To date, 12 chemical groups have been constructed and added to the pool of chemicals that can be selected for Biomonitoring California studies, including p,p´-bisphenols, brominated and chlorinated organic compounds used as flame retardants, non-halogenated aromatic phosphates, and synthetic polycyclic musks. Evaluating chemical groups, rather than individual chemicals, is an efficient way to respond to shifts in chemical use and the emergence of new chemicals. This strategy can enable earlier identification of important chemicals for monitoring and intervention. PMID:27905275

Guidelines for pre-clinical animal and cellular models of MuSK-myasthenia gravis.

PubMed

Phillips, W D; Christadoss, P; Losen, M; Punga, A R; Shigemoto, K; Verschuuren, J; Vincent, A

2015-08-01

Muscle-specific tyrosine kinase (MuSK) autoantibodies are the hallmark of a form of myasthenia gravis (MG) that can challenge the neurologist and the experimentalist. The clinical disease can be difficult to treat effectively. MuSK autoantibodies affect the neuromuscular junction in several ways. When added to muscle cells in culture, MuSK antibodies disperse acetylcholine receptor clusters. Experimental animals actively immunized with MuSK develop MuSK autoantibodies and muscle weakness. Weakness is associated with reduced postsynaptic acetylcholine receptor numbers, reduced amplitudes of miniature endplate potentials and endplate potentials, and failure of neuromuscular transmission. Similar impairments have been found in mice injected with IgG from MG patients positive for MuSK autoantibody (MuSK-MG). The active and passive models have begun to reveal the mechanisms by which MuSK antibodies disrupt synaptic function at the neuromuscular junction, and should be valuable in developing therapies for MuSK-MG. However, translation into new and improved treatments for patients requires procedures that are not too cumbersome but suitable for examining different aspects of MuSK function and the effects of potential therapies. Study design, conduct and analysis should be carefully considered and transparently reported. Here we review what has been learnt from animal and culture models of MuSK-MG, and offer guidelines for experimental design and conduct of studies, including sample size determination, randomization, outcome parameters and precautions for objective data analysis. These principles may also be relevant to the increasing number of other antibody-mediated diseases that are now recognized. Copyright © 2014 Elsevier Inc. All rights reserved.

FORMATION OF NITRO MUSK ADDUCTS OF RAINBOW TROUT HEMOGLOBIN FOR POTENTIAL USE AS BIOMARKERS OF EXPOSURE

EPA Science Inventory

The high use of nitro musk xylene (MX) and musk ketone (MK) as fragrances, and their persistence and bioaccumulation potential make them ubiquitous environmental contaminants. The 4-amino-MX (AMX) and 2-amino-MK (AMK) metabolites have been detected in trout fish hemoglobin (Hb) s...

Comparative Analysis of the Gut Microbial Communities in Forest and Alpine Musk Deer Using High-Throughput Sequencing

PubMed Central

Hu, Xiaolong; Liu, Gang; Shafer, Aaron B. A.; Wei, Yuting; Zhou, Juntong; Lin, Shaobi; Wu, Haibin; Zhou, Mi; Hu, Defu; Liu, Shuqiang

2017-01-01

The gut ecosystem is characterized by dynamic and reciprocal interactions between the host and bacteria. Although characterizing microbiota for herbivores has become recognized as important tool for gauging species health, no study to date has investigated the bacterial communities and evaluated the age-related bacterial dynamics of musk deer. Moreover, gastrointestinal diseases have been hypothesized to be a limiting factor of population growth in captive musk deer. Here, high-throughput sequencing of the bacterial 16S rRNA gene was used to profile the fecal bacterial communities in juvenile and adult alpine and forest musk deer. The two musk deer species harbored similar bacterial communities at the phylum level, whereas the key genera for the two species were distinct. The bacterial communities were dominated by Firmicutes and Bacteroidetes, with the bacterial diversity being higher in forest musk deer. The Firmicutes to Bacteroidetes ratio also increased from juvenile to adult, while the bacterial diversity, within-group and between-group similarity, all increased with age. This work serves as the first sequence-based analysis of variation in bacterial communities within and between musk deer species, and demonstrates how the gut microbial community dynamics vary among closely related species and shift with age. As gastrointestinal diseases have been observed in captive populations, this study provides valuable data that might benefit captive management and future reintroduction programs. PMID:28421061

High Frontier, The Journal for Space & Missile Professionals. Volume 3, Number 3, May 2007

DTIC Science & Technology

2007-05-01

Superiority in the 21st Century Mr. Elon Musk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27...progress new technologies. From the “Industry Perspective,” we’re fortunate to capture views from Mr. Elon Musk , CEO and CTO of Space Exploration...High Frontier Space Superiority in the 21st Century Mr. Elon Musk CEO and CTO Space

Emendation and new species of Hapalorhynchus Stunkard, 1922 (Digenea: Schistosomatoidea) from musk turtles (Kinosternidae: Sternotherus) in Alabama and Florida rivers.

PubMed

Roberts, Jackson R; Halanych, Kenneth M; Arias, Cova R; Folt, Brian; Goessling, Jeffrey M; Bullard, Stephen A

2017-12-01

Hapalorhynchus Stunkard, 1922 is emended based on morphological study of existing museum specimens (type and voucher specimens) and newly-collected specimens infecting musk turtles (Testudines: Kinosternidae: Sternotherus spp.) from rivers in Alabama and Florida (USA). Hapalorhynchus conecuhensis n. sp. is described from an innominate musk turtle, Sternotherus cf. minor, (type host) from Blue Spring (31°5'27.64″N, 86°30'53.21″W; Pensacola Bay Basin, Alabama) and the loggerhead musk turtle, Sternotherus minor (Agassiz, 1857) from the Wacissa River (30°20'24.73″N, 83°59'27.56″W; Apalachee Bay Basin, Florida). It differs from congeners by lacking a body constriction at level of the ventral sucker, paired anterior caeca, and a transverse ovary as well as by having a small ventral sucker, proportionally short posterior caeca, nearly equally-sized anterior and posterior testes, a small cirrus sac, and a uterus extending dorsal to the ovary and the anterior testis. Specimens of Hapalorhynchus reelfooti Byrd, 1939 infected loggerhead musk turtles, stripe-necked musk turtles (Sternotherus peltifer Smith and Glass, 1947), Eastern musk turtles (Sternotherus odoratus [Latreille in Sonnini and Latreille, 1801]), and S. cf. minor. Those of Hapalorhynchus cf. stunkardi infected S. minor and S. odoratus. Sternothorus minor, S. peltifer, and S. cf. minor plus S. minor and S. odoratus are new host records for H. reelfooti and H. cf. stunkardi, respectively. This is the first report of an infected musk turtle from the Coosa and Tallapoosa Rivers (Mobile-Tensaw River Basin), Pensacola Bay Basin, or Apalachee Bay Basin. Sequence analysis of the large subunit rDNA (28S) showed a strongly-supported clade for Hapalorhynchus. Copyright © 2017 Elsevier B.V. All rights reserved.

Examination of the Benefits of Standardized Interfaces on Space Systems

DTIC Science & Technology

2015-09-01

them to enter the once impenetrable aerospace market: Elon Musk with Space Exploration Technologies (SpaceX), Richard Branson with Virgin Galactic, and...systems-engineering- guide/se-life cycle-building-blocks/concept-development/highlevel-conceptual- definition. Musk , Elon . 2009. Risky Business... Musk , 2009) Unknown effects of prolonged exposure to radiation Degraded system capability (JPL 2015) Replenishment of the system capability may

Amine-functionalized MIL-53(Al)-coated stainless steel fiber for efficient solid-phase microextraction of synthetic musks and organochlorine pesticides in water samples.

PubMed

Xie, Lijun; Liu, Shuqin; Han, Zhubing; Jiang, Ruifen; Zhu, Fang; Xu, Weiqin; Su, Chengyong; Ouyang, Gangfeng

2017-09-01

The fiber coating is the key part of the solid-phase microextraction (SPME) technique, and it determines the sensitivity, selectivity, and repeatability of the analytical method. In this work, amine (NH 2 )-functionalized material of Institute Lavoisier (MIL)-53(Al) nanoparticles were successfully synthesized, characterized, and applied as the SPME fiber coating for efficient sample pretreatment owing to their unique structures and excellent adsorption properties. Under optimized conditions, the NH 2 -MIL-53(Al)-coated fiber showed good precision, low limits of detection (LODs) [0.025-0.83 ng L -1 for synthetic musks (SMs) and 0.051-0.97 ng L -1 for organochlorine pesticides (OCPs)], and good linearity. Experimental results showed that the NH 2 -MIL-53(Al) SPME coating was solvent resistant and thermostable. In addition, the extraction efficiencies of the NH 2 -MIL-53(Al) coating for SMs and OCPs were higher than those of commercially available SPME fiber coatings such as polydimethylsiloxane, polydimethylsiloxane-divinylbenzene, and polyacrylate. The reasons may be that the analytes are adsorbed on NH 2 -MIL-53(Al) primarily through π-π interactions, electron donor-electron acceptor interactions, and hydrogen bonds between the analytes and organic linkers of the material. Direct immersion (DI) SPME-gas chromatography-mass spectrometry methods based on NH 2 -MIL-53(Al) were successfully applied for the analysis of tap and river water samples. The recoveries were 80.3-115% for SMs and 77.4-117% for OCPs. These results indicate that the NH 2 -MIL-53(Al) coating may be a promising alternative to SPME coatings for the enrichment of SMs and OCPs.

Inhibition of Polyisoprenylated Methylated Protein Methyl Esterase by Synthetic Musks Induces Cell Degeneration

PubMed Central

Ayuk-Takem, Lambert; Amissah, Felix; Aguilar, Byron J.; Lamango, Nazarius S.

2013-01-01

Synthetic fragrances are persistent environmental pollutants that tend to bioaccumulate in animal tissues. They are widely used in personal care products and cleaning agents. Worldwide production of Galaxolide and Tonalide are in excess of 4500 tons annually. Because of their widespread production and use, they have been detected in surface waters and fish in the US and Europe. Consumption of contaminated water and fish from such sources leads to bioaccumulation and eventual toxicity. Since fragrances and flavors bear structural similarities to polyisoprenes, it was of interest to determine whether toxicity by Galaxolide and Tonalide may be linked with polyisoprenylated methylated protein methyl esterase (PMPMEase) inhibition. A concentration-dependent study of PMPMEase inhibition by Galaxolide and Tonalide as well as their effects on the degeneration of cultured cells were conducted. Galaxolide and Tonalide inhibited purified porcine liver PMPMEase with Ki values of 11 and 14 µM, respectively. Galaxolide and Tonalide also induced human cancer cell degeneration with EC50 values of 26 and 98 µM (neuroblastoma SH-SY5Y cells) and 58 and 14 µM (lung cancer A549 cells), respectively. The effects on cell viability correlate well with the inhibition of PMPMEase activity in the cultured cells. Molecular docking analysis revealed that the binding interactions are most likely between the fragrance molecules and hydrophobic amino acids in the active site of the enzyme. These results appear to suggest that the reported neurotoxicity of these compounds may be associated with their inhibition of PMPMEase. Exposure to fragrances may pose a significant risk to individuals predisposed to developing degenerative disorders. PMID:22489002

Space Industry

DTIC Science & Technology

2006-01-01

invest in and support commercial efforts. In testimony before the House Committee on Space and Aeronautics in April of 2005, Elon Musk provided the...Response Launch Vehicle. Space Daily. Retrieved April 9, 2006 from www.spacedaily.com. 81 Musk , Elon (2005, April 20). Commercialization of Space...Space Transportation Policy. (2006, January 5). Retrieved May 30, 2006 from http://www.ostp.gov/html/SpaceTransFactSheetJan2005.pdf. 86 Musk , Elon

Pressurized liquid extraction-gas chromatography-mass spectrometry analysis of fragrance allergens, musks, phthalates and preservatives in baby wipes.

PubMed

Celeiro, Maria; Lamas, J Pablo; Garcia-Jares, Carmen; Llompart, Maria

2015-03-06

Baby wipes and wet toilet paper are specific hygiene care daily products used on newborn and children skin. These products may contain complexes mixtures of harmful chemicals. A method based on pressurized liquid extraction (PLE) followed by gas chromatography-mass spectrometry (GC-MS) has been developed for the simultaneous determination of sixty-five chemical compounds (fragrance allergens, preservatives, musks, and phthalates) in wipes and wet toilet paper for children. These compounds are legislated in Europe according Regulation EC No 1223/2009, being twelve of them banned for their use in cosmetics, and one of them, 3-iodo-2-propynyl butylcarbamate (IPBC), is banned in products intended for children under 3 years. Also, propyl-, and butylparaben will be prohibited in leave-on cosmetic products designed for application on the nappy area of children under 3 years from April 2015. PLE is a fast, simple, easily automated technique, which permits to integrate a clean-up step during the extraction process reducing analysis time and stages. The proposed PLE-based procedure was optimized on real non-spiked baby wipe samples by means of experimental design to study the influence on extraction of parameters such as extraction solvent, temperature, extraction time, and sorbent type. Under the selected conditions, the method was validated showing satisfactory linearity, and intra-day, and inter-day precision. Recoveries were between 80-115% for most of the compounds with relative standard deviations (RSD) lower than 15%. Finally, twenty real samples were analyzed. Thirty-six of the target analytes were detected, highlighting the presence of phenoxyethanol in all analyzed samples at high concentration levels (up to 0.8%, 800μgg(-1)). Methyl paraben (MeP), and ethyl paraben (EtP) were found in 40-50% of the samples, and the recently banned isobutyl paraben (iBuP) and isopropyl paraben (iPrP), were detected in one and seven samples, respectively, at concentrations between 0.093 and 247μgg(-1). In the case of phthalates, the forbidden phthalates dibutyl phtalate (DBP) and di(2-ethylhexyl)phthalate (DEHP) were also found in thirteen samples at low levels. All the samples contained fragrance allergens in many cases at high levels (up to 2400μgg(-1)) and three musks were detected in the samples. Excluding the banned compounds, all samples complied with the concentration limits established by the European Regulation although 25% of them did not fulfill the labeling requirements for fragrance allergens. Copyright © 2015 Elsevier B.V. All rights reserved.

A comparative study of sex difference in calbindin neurons among mice, musk shrews, and Japanese quails.

PubMed

Moe, Yadanar; Tanaka, Tomoko; Morishita, Masahiro; Ohata, Ryoko; Nakahara, Chihiro; Kawashima, Takaharu; Maekawa, Fumihiko; Sakata, Ichiro; Sakai, Takafumi; Tsukahara, Shinji

2016-09-19

The medial preoptic nucleus (MPN) and the bed nucleus of the stria terminalis (BNST) of mice contain sexually dimorphic nuclei (SDNs) that are larger and have more neurons expressing calbindin D-28K (CB), a calcium-binding protein, in males than females. However, it is largely unknown whether such SDNs exist in species other than rodents. In this study, we performed an immunohistochemical study of CB in the MPN and BNST of musk shrews and Japanese quails to examine the existence of homologs of SDNs in mice. Like mice, musk shrews had a SDN exhibiting male-biased sex differences in volume and CB-immunoreactive (ir) cell number in the MPN. The BNST of musk shrews also contained a male-biased SDN, but consisted of non-CB neurons. The paratenial thalamic nucleus of musk shrews, but not mice, had more CB-ir cells in males than females. In Japanese quails of both sexes, CB-ir cells in the MPN and BNST were extremely small in number and did not cluster. These results suggest that the distribution of CB neurons differs among these species. Musk shrews may have a homolog of the SDN composed of CB neurons in the MPN of mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Skunk musk causes methemoglobin and Heinz body formation in vitro.

PubMed

Fierro, Brittney R; Agnew, Dalen W; Duncan, Ann E; Lehner, Andreas F; Scott, Michael A

2013-09-01

A captive Red Panda developed a regenerative anemia with Heinz bodies after being sprayed by a skunk. A definite cause-and-effect relationship between skunk musk and oxidative erythrocyte damage has not been reported, but it was suspected in one reported case of a dog with Heinz body hemolytic anemia. The objective was to determine whether skunk musk induces oxidative HGB damage in vitro. Plasma and RBC were harvested from heparinized blood of 3 dogs, 3 cats, and a Red Panda. Skunk musk was solubilized in ethanol and mixed with plasma from each species to make stock solutions of 4% musk and 4% ethanol. Aliquots of RBC were resuspended in autologous stock solutions and solvent controls to yield musk concentrations of 0%, 0.04%, and 0.4% (by volume). Aliquots were incubated at 37°C for 4-72 hours and assessed for oxidative damage by visual inspection, optical absorbance spectroscopy, transmission electron microscopy, and light microscopy after Wright and vital New Methylene Blue staining. Dose-dependent brown color and absorption changes characteristic of methemoglobin were present by 4 hours and increased over 24 hours (Red Panda) and 72 hours (dog and cat). Similarly, there were time-dependent (all species) and dose-dependent (dog and cat) increases in the number of Heinz bodies, which were present by 4 hours and numerous by 24 hours. In vitro, skunk musk causes Heinz body and methemoglobin formation in canine, feline, and Red Panda RBC, supporting the clinical association between Heinz body hemolytic anemia and skunk spray exposure. © 2013 American Society for Veterinary Clinical Pathology.

Ancient DNA analyses exclude humans as the driving force behind late Pleistocene musk ox (Ovibos moschatus) population dynamics

PubMed Central

Campos, Paula F.; Willerslev, Eske; Sher, Andrei; Orlando, Ludovic; Axelsson, Erik; Tikhonov, Alexei; Aaris-Sørensen, Kim; Greenwood, Alex D.; Kahlke, Ralf-Dietrich; Kosintsev, Pavel; Krakhmalnaya, Tatiana; Kuznetsova, Tatyana; Lemey, Philippe; MacPhee, Ross; Norris, Christopher A.; Shepherd, Kieran; Suchard, Marc A.; Zazula, Grant D.; Shapiro, Beth; Gilbert, M. Thomas P.

2010-01-01

The causes of the late Pleistocene megafaunal extinctions are poorly understood. Different lines of evidence point to climate change, the arrival of humans, or a combination of these events as the trigger. Although many species went extinct, others, such as caribou and bison, survived to the present. The musk ox has an intermediate story: relatively abundant during the Pleistocene, it is now restricted to Greenland and the Arctic Archipelago. In this study, we use ancient DNA sequences, temporally unbiased summary statistics, and Bayesian analytical techniques to infer musk ox population dynamics throughout the late Pleistocene and Holocene. Our results reveal that musk ox genetic diversity was much higher during the Pleistocene than at present, and has undergone several expansions and contractions over the past 60,000 years. Northeast Siberia was of key importance, as it was the geographic origin of all samples studied and held a large diverse population until local extinction at ≈45,000 radiocarbon years before present (14C YBP). Subsequently, musk ox genetic diversity reincreased at ca. 30,000 14C YBP, recontracted at ca. 18,000 14C YBP, and finally recovered in the middle Holocene. The arrival of humans into relevant areas of the musk ox range did not affect their mitochondrial diversity, and both musk ox and humans expanded into Greenland concomitantly. Thus, their population dynamics are better explained by a nonanthropogenic cause (for example, environmental change), a hypothesis supported by historic observations on the sensitivity of the species to both climatic warming and fluctuations. PMID:20212118

Removal of polycyclic synthetic musks and antineoplastic drugs in ozonated wastewater: Quantitation based on the data of differential spectroscopy.

PubMed

Li, Wei; Nanaboina, Venkateswarlu; Chen, Fang; Korshin, Gregory V

2016-03-05

This study examined the degradation behavior of polycyclic musks (PMs) and antineoplastic drugs (ADs) and the absorbance spectra of effluent organic matter (EfOM) in municipal wastewater by ozone. Specific ozone doses used in the experiments ranged from 0 to 1mg O3/mg dissolved organic matter (DOC). The examined PMs included galaxolide, tonalide, celestolide, traseolide and phantolide. ADs included busulfan, chlorambucil, cyclophosphamide, dacarbazine, flutamide, ifosfamide, tamoxifen and methotrexate. Strong monotonic albeit nonlinear correlations were found to exist between relative changes of EfOM absorbance at 254 nm (i.e. ΔA254/A(0)254) and the degradation of the selected PMs and ADs. This result was interpreted based on the concept of the simultaneous oxidation of EfOM and, on the other hand, PMs and ADs. This interpretation showed that PMs were degraded primarily via OH radical attack, with tonalide and phantolide being less reactive compared with the other PMs. ADs such as cyclophosphamide, ifosfamide and busulfan were also determined to undergo oxidation by OH radicals. Comparison of the behavior of the radical probe para-chlorobenzoic acid and the examined ADs and PMs allowed evaluating corresponding reaction rate constants for reactions between these species and OH radicals. Copyright © 2015 Elsevier B.V. All rights reserved.

Converting a Manned LCU into an Unmanned Surface Vehicle (USV): An Open Systems Architecture (OSA) Case Study

DTIC Science & Technology

2014-09-01

pdf. Musk , Elon . 2014. Statement Of Elon Musk , Ceo & Chief Designer, Space Exploration Technologies Corp. (Spacex), Before The Committee On...every year moving forward ( Musk 2014)? These questions build the framework for executing OSA throughout an SE program. The OSA framework includes a...systems must be well maintained to the current legal environment. Maintaining this doctrine requires a continuous feedback loop from unmanned systems

IgG4 autoantibodies against muscle-specific kinase undergo Fab-arm exchange in myasthenia gravis patients.

PubMed

Koneczny, Inga; Stevens, Jo A A; De Rosa, Anna; Huda, Saif; Huijbers, Maartje G; Saxena, Abhishek; Maestri, Michelangelo; Lazaridis, Konstantinos; Zisimopoulou, Paraskevi; Tzartos, Socrates; Verschuuren, Jan; van der Maarel, Silvère M; van Damme, Philip; De Baets, Marc H; Molenaar, Peter C; Vincent, Angela; Ricciardi, Roberta; Martinez-Martinez, Pilar; Losen, Mario

2017-02-01

Autoimmunity mediated by IgG4 subclass autoantibodies is an expanding field of research. Due to their structural characteristics a key feature of IgG4 antibodies is the ability to exchange Fab-arms with other, unrelated, IgG4 molecules, making the IgG4 molecule potentially monovalent for the specific antigen. However, whether those disease-associated antigen-specific IgG4 are mono- or divalent for their antigens is unknown. Myasthenia gravis (MG) with antibodies to muscle specific kinase (MuSK-MG) is a well-recognized disease in which the predominant pathogenic IgG4 antibody binds to extracellular epitopes on MuSK at the neuromuscular junction; this inhibits a pathway that clusters the acetylcholine (neurotransmitter) receptors and leads to failure of neuromuscular transmission. In vitro Fab-arm exchange-inducing conditions were applied to MuSK antibodies in sera, purified IgG4 and IgG1-3 sub-fractions. Solid-phase cross-linking assays were established to determine the extent of pre-existing and inducible Fab-arm exchange. Functional effects of the resulting populations of IgG4 antibodies were determined by measuring inhibition of agrin-induced AChR clustering in C2C12 cells. To confirm the results, κ/κ, λ/λ and hybrid κ/λ IgG4s were isolated and tested for MuSK antibodies. At least fifty percent of patients had IgG4, but not IgG1-3, MuSK antibodies that could undergo Fab-arm exchange in vitro under reducing conditions. Also MuSK antibodies were found in vivo that were divalent (monospecific for MuSK). Fab-arm exchange with normal human IgG4 did not prevent the inhibitory effect of serum derived MuSK antibodies on AChR clustering in C2C12 mouse myotubes. The results suggest that a considerable proportion of MuSK IgG4 could already be Fab-arm exchanged in vivo. This was confirmed by isolating endogenous IgG4 MuSK antibodies containing both κ and λ light chains, i.e. hybrid IgG4 molecules. These new findings demonstrate that Fab-arm exchanged antibodies are pathogenic. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

LEVELS OF SYNTHETIC MUSKS COMPOUNDS IN ...

EPA Pesticide Factsheets

There is no abstract available for this product. If further information is requested, please refer to the bibliographic citation and contact the person listed under Contact field. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various research projects being performed in support of this Task and more in-depth coverage of each project. Briefly, each project's objective is stated below.Subtask 1: To integrate state-of-the-art technologies (polar organic chemical integrative samplers, advanced solid-phase extraction methodologies with liquid chromatography/electrospray/mass spectrometry) and apply them to studying the sources and fate of a select list of PPCPs. Application and improvement of analytical methodologies that can detect non-volatile, polar, water-soluble pharmaceuticals in source waters at levels that could be environmentally significant (at concentrations less than parts per billion, ppb). IAG with USGS ends in FY05. APM 20 due in FY05.Subtask 2: Coordination of interagency research and public outreach activities for PPCPs. Participate on NSTC Health and Environment subcommittee working group on PPCPs. Web site maintenance and expansion, invited technical presentations, invited articles for peer-reviewed journals, interviews for media, responding to public inquiries. S

Reconsidering the Rules for Space Security

DTIC Science & Technology

2008-04-01

orbit.187 Elon Musk , the owner of SpaceX, has invested $100 mil- lion of his own money and hopes to recoup his investment by developing another rocket...2007, http://www.space.com/news/070328_spacex_falc1test_updt.html. 188. NSSLRP, National Security Space Launch Report, 35. 189. Musk is currently...expen- sive than he anticipated. Even before the March 2006 inaugural Falcon 1 launch failure, Musk had invested twice as much of his own money in SpaceX

Strong Artificial Intelligence and National Security: Operational and Strategic Implications

DTIC Science & Technology

2015-05-18

including Tesla/Space X founder Elon Musk and theoretical physicist Stephen Hawking, released an open letter warning of the existential risk presented by...the MIT Aeronautics and Astronautics Department’s 2014 Centennial Symposium, Elon Musk , a member of FLI, said that creating such a capable...pentagram and the holy water, it’s like yeah he’s sure he can control the demon. Didn’t work out.” Elon Musk , interview by Jaime Peraire, 2014

Musk Oxen and Micelles

NASA Astrophysics Data System (ADS)

Hill, John W.

1996-09-01

Musk oxen behavior provides an analogy to micelle formation by amphipathic substances. Mature male musk oxen protect their young and females from wolves by forming a protective circle around them. The males stand with their tails to the inside and their heads facing outward. Amphipathic substances such as soap form micelles. The hydrophobic hydrocarbon tails of the soap are turned to the inside of the micelle and the hydrophilic carboxylate heads are on the outside at the interface with the polar water molecules.

Maintenance plasma exchange treatment for muscle specific kinase antibody positive myasthenia gravis patients.

PubMed

Yamada, Chisa; Teener, James W; Davenport, Robertson D; Cooling, Laura

2015-10-01

Anti-muscle specific kinase antibody positive myasthenia gravis (MuSK MG) is often characterized by a relatively severe and progressive course, refractoriness to standard myasthenia gravis (MG) medications, and an increased risk of myasthenic crisis. We report here successful management of three MuSK MG patients using maintenance therapeutic plasma exchange (TPE) treatment for up to 4.5 years. The study was a 5-year retrospective review of all MG patients treated with TPE between 2008 and 2013 at University of Michigan. Inclusion criteria of MuSK MG were positive for anti-MuSK antibodies and a diagnosis of MuSK MG by staff neurologists. Patient data included age, gender, diagnostic testing results, medications, and the dates and response to TPE treatments. A total of 153 MG patients underwent at least one course of TPE between 2008 and 2013. A total of 12 patients (7.8%) were positive for anti-MuSK antibodies. Patients were predominantly female (83.3%) and a median age of onset was 46-years old. Three MuSK MG patients were successfully managed with maintenance TPE. Maintenance TPE may be an effective option for MuSK MG patients. The key of successful maintenance treatment at our institution has been to tailor the TPE frequency for each individual, and to modify the treatment interval in conjunction with medical management. © 2014 Wiley Periodicals, Inc.

Autoantibody-producing plasmablasts after B cell depletion identified in muscle-specific kinase myasthenia gravis

PubMed Central

Stathopoulos, Panos; Kumar, Aditya; Nowak, Richard J.; O’Connor, Kevin C.

2017-01-01

Myasthenia gravis (MG) is a B cell–mediated autoimmune disorder of neuromuscular transmission. Pathogenic autoantibodies to muscle-specific tyrosine kinase (MuSK) can be found in patients with MG who do not have detectable antibodies to the acetylcholine receptor (AChR). MuSK MG includes immunological and clinical features that are generally distinct from AChR MG, particularly regarding responsiveness to therapy. B cell depletion has been shown to affect a decline in serum autoantibodies and to induce sustained clinical improvement in the majority of MuSK MG patients. However, the duration of this benefit may be limited, as we observed disease relapse in MuSK MG patients who had achieved rituximab-induced remission. We investigated the mechanisms of such relapses by exploring autoantibody production in the reemerging B cell compartment. Autoantibody-expressing CD27+ B cells were observed within the reconstituted repertoire during relapse but not during remission or in controls. Using two complementary approaches, which included production of 108 unique human monoclonal recombinant immunoglobulins, we demonstrated that antibody-secreting CD27hiCD38hi B cells (plasmablasts) contribute to the production of MuSK autoantibodies during relapse. The autoantibodies displayed hallmarks of antigen-driven affinity maturation. These collective findings introduce potential mechanisms for understanding both MuSK autoantibody production and disease relapse following B cell depletion. PMID:28878127

The Cytoplasmic Adaptor Protein Dok7 Activates the Receptor Tyrosine Kinase MuSK via Dimerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergamin, E.; Hallock, P; Burden, S

Formation of the vertebrate neuromuscular junction requires, among others proteins, Agrin, a neuronally derived ligand, and the following muscle proteins: LRP4, the receptor for Agrin; MuSK, a receptor tyrosine kinase (RTK); and Dok7 (or Dok-7), a cytoplasmic adaptor protein. Dok7 comprises a pleckstrin-homology (PH) domain, a phosphotyrosine-binding (PTB) domain, and C-terminal sites of tyrosine phosphorylation. Unique among adaptor proteins recruited to RTKs, Dok7 is not only a substrate of MuSK, but also an activator of MuSK's kinase activity. Here, we present the crystal structure of the Dok7 PH-PTB domains in complex with a phosphopeptide representing the Dok7-binding site on MuSK.more » The structure and biochemical data reveal a dimeric arrangement of Dok7 PH-PTB that facilitates trans-autophosphorylation of the kinase activation loop. The structure provides the molecular basis for MuSK activation by Dok7 and for rationalizing several Dok7 loss-of-function mutations found in patients with congenital myasthenic syndromes.« less

Agrin-LRP4-MuSK signaling as a therapeutic target for myasthenia gravis and other neuromuscular disorders.

PubMed

Ohno, Kinji; Ohkawara, Bisei; Ito, Mikako

2017-10-01

Signal transduction at the neuromuscular junction (NMJ) is compromised in a diverse array of diseases including myasthenia gravis, Lambert-Eaton myasthenic syndrome, Isaacs' syndrome, congenital myasthenic syndromes, Fukuyama-type congenital muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia. Except for sarcopenia, all are orphan diseases. In addition, the NMJ signal transduction is impaired by tetanus, botulinum, curare, α-bungarotoxin, conotoxins, organophosphate, sarin, VX, and soman to name a few. Areas covered: This review covers the agrin-LRP4-MuSK signaling pathway, which drives clustering of acetylcholine receptors (AChRs) and ensures efficient signal transduction at the NMJ. We also address diseases caused by autoantibodies against the NMJ molecules and by germline mutations in genes encoding the NMJ molecules. Expert opinion: Representative small compounds to treat the defective NMJ signal transduction are cholinesterase inhibitors, which exert their effects by increasing the amount of acetylcholine at the synaptic space. Another possible therapeutic strategy to enhance the NMJ signal transduction is to increase the number of AChRs, but no currently available drug has this functionality.

The QSPR-THESAURUS: the online platform of the CADASTER project.

PubMed

Brandmaier, Stefan; Peijnenburg, Willie; Durjava, Mojca K; Kolar, Boris; Gramatica, Paola; Papa, Ester; Bhhatarai, Barun; Kovarich, Simona; Cassani, Stefano; Roy, Partha Pratim; Rahmberg, Magnus; Öberg, Tomas; Jeliazkova, Nina; Golsteijn, Laura; Comber, Mike; Charochkina, Larisa; Novotarskyi, Sergii; Sushko, Iurii; Abdelaziz, Ahmed; D'Onofrio, Elisa; Kunwar, Prakash; Ruggiu, Fiorella; Tetko, Igor V

2014-03-01

The aim of the CADASTER project (CAse Studies on the Development and Application of in Silico Techniques for Environmental Hazard and Risk Assessment) was to exemplify REACH-related hazard assessments for four classes of chemical compound, namely, polybrominated diphenylethers, per and polyfluorinated compounds, (benzo)triazoles, and musks and fragrances. The QSPR-THESAURUS website (http: / /qspr-thesaurus.eu) was established as the project's online platform to upload, store, apply, and also create, models within the project. We overview the main features of the website, such as model upload, experimental design and hazard assessment to support risk assessment, and integration with other web tools, all of which are essential parts of the QSPR-THESAURUS. 2014 FRAME.

Simultaneous determination of polycyclic musks in blood and urine by solid supported liquid-liquid extraction and gas chromatography-tandem mass spectrometry.

PubMed

Liu, Hongtao; Huang, Liping; Chen, Yuxin; Guo, Liman; Li, Limin; Zhou, Haiyun; Luan, Tiangang

2015-06-15

A rapid, precise and accurate method for the simultaneous determination of 5 polycyclic musks (PCMs) in biological fluids was developed by solid supported liquid-liquid extraction (SLE) coupled with gas chromatography-tandem mass spectrometry (GC-MS/MS). All parameters influencing SLE-GC-MS performance, including electron energy of electron-impact ionization source, collision energy for tandem mass spectrometer when operated in selected-reaction monitoring (SRM) mode, type and volume of elution reagent, nitrogen evaporation time, pH and salinity of sample have been carefully optimized. Eight milliliter of n-hexane was finally chosen as elution reagent. Blood and urine sample could be loaded into SLE cartridge without adjusting pH and salinity. Deuterated tonalide (AHTN-d3) was chosen as internal standard. The correlation coefficient (r(2)) of the calibration curves of target compounds ranged from 0.9996 to 0.9998. The dynamic range spanned over two orders of magnitude. The limit of detection (LOD) of target compounds in blood and urine ranged from 0.008 to 0.105μgL(-1) and 0.005 to 0.075μgL(-1), respectively. The developed procedure was successfully applied to the analysis of PCMs in human blood and urine obtaining satisfying recoveries on low, medium and high levels. The method was compared with SLE-GC-MS and shown one to two orders of magnitude improvement in sensitivity. Copyright © 2015 Elsevier B.V. All rights reserved.

LRP4 is critical for neuromuscular junction maintenance.

PubMed

Barik, Arnab; Lu, Yisheng; Sathyamurthy, Anupama; Bowman, Andrew; Shen, Chengyong; Li, Lei; Xiong, Wen-cheng; Mei, Lin

2014-10-15

The neuromuscular junction (NMJ) is a synapse between motor neurons and skeletal muscle fibers, and is critical for control of muscle contraction. Its formation requires neuronal agrin that acts by binding to LRP4 to stimulate MuSK. Mutations have been identified in agrin, MuSK, and LRP4 in patients with congenital myasthenic syndrome, and patients with myasthenia gravis develop antibodies against agrin, LRP4, and MuSK. However, it remains unclear whether the agrin signaling pathway is critical for NMJ maintenance because null mutation of any of the three genes is perinatal lethal. In this study, we generated imKO mice, a mutant strain whose LRP4 gene can be deleted in muscles by doxycycline (Dox) treatment. Ablation of the LRP4 gene in adult muscle enabled studies of its role in NMJ maintenance. We demonstrate that Dox treatment of P30 mice reduced muscle strength and compound muscle action potentials. AChR clusters became fragmented with diminished junctional folds and synaptic vesicles. The amplitude and frequency of miniature endplate potentials were reduced, indicating impaired neuromuscular transmission and providing cellular mechanisms of adult LRP4 deficiency. We showed that LRP4 ablation led to the loss of synaptic agrin and the 90 kDa fragments, which occurred ahead of other prejunctional and postjunctional components, suggesting that LRP4 may regulate the stability of synaptic agrin. These observations demonstrate that LRP4 is essential for maintaining the structural and functional integrity of the NMJ and that loss of muscle LRP4 in adulthood alone is sufficient to cause myasthenic symptoms. Copyright © 2014 the authors 0270-6474/14/3413892-14$15.00/0.

America’s Air Force, The Future Calls: An Evidentiary and Theoretical Analysis Of The Roles And Missions Of A USAF Astronaut Corps

DTIC Science & Technology

2016-06-01

wT0S8qQLCOqh. ; Keith Wagstaff, “ Elon Musk Says SpaceX Will Send People to Mars By 2025,” NBC News, 29 January 2016, Accessed 22 February 2016...http://www.nbcnews.com/tech/tech-news/ elon - musk -says-spacex-will-send-people- mars-2025-n506891. 76. “About Mars One,” Mars-One.com, 2016, Accessed 22...January 2014. Accessed 22 February 2016. https://www.stratcom.mil/factsheets/11/Space_Control_and_Space_Surveillan ce/. Wagstaff, Keith. “ Elon Musk Says

Recessive variants of MuSK are associated with late onset CMS and predominant limb girdle weakness.

PubMed

Owen, David; Töpf, Ana; Preethish-Kumar, Veeramani; Lorenzoni, Paulo José; Vroling, Bas; Scola, Rosana Herminia; Dias-Tosta, Elza; Geraldo, Argemiro; Polavarapu, Kiran; Nashi, Saraswati; Cox, Daniel; Evangelista, Teresinha; Dawson, John; Thompson, Rachel; Senderek, Jan; Laurie, Steven; Beltran, Sergi; Gut, Marta; Gut, Ivo; Nalini, Atchayaram; Lochmüller, Hanns

2018-04-28

Congenital myasthenic syndrome (CMS) is a heterogeneous disorder that causes fatigable muscle weakness. CMS has been associated with variants in the MuSK gene and, to date, 16 patients have been reported. MuSK-CMS patients present a different phenotypic pattern of limb girdle weakness. Here, we describe four additional patients and discuss the phenotypic and clinical relationship with those previously reported. Two novel damaging missense variants are described: c.1742T > A; p.I581N found in homozygosis, and c.1634T > C; p.L545P found in compound heterozygosis with p.R166*. The reported patients had predominant limb girdle weakness with symptom onset at 12, 17, 18, and 30 years of age, and the majority exhibited a good clinical response to Salbutamol therapy, but not to esterase inhibitors. Meta-analysis including previously reported variants revealed an increased likelihood of a severe, respiratory phenotype with null alleles. Missense variants exclusively affecting the kinase domain, but not the catalytic site, are associated with late onset. These data refine the phenotype associated with MuSK-related CMS. © 2018 Wiley Periodicals, Inc.

Michael Griffin Meets with Elon Musk

NASA Image and Video Library

2005-04-19

NASA Administrator Michael Griffin, left, meets with CEO of SpaceX Elon Musk, right, Wednesday, April 20, 2005 at NASA Headquarters in Washington. Looking on in the background are Larry Williams, NASA astronaut Marsha Ivins and NASA manager Christopher Shank. Photo Credit: (NASA/Renee Bouchard)

78 FR 35931 - Granting of Request for Early Termination of the Waiting Period Under the Premerger Notification...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-14

..., Inc.; Sage Parent Company, Inc.; Herff Jones, Inc. 20130875 G Eastman Kodak Company; Eastman Kodak Company; Eastman Kodak Company. 05/28/2013 20130871 G Elon Musk; Tesla Motors, Inc.; Elon Musk. 05/29/2013...

Regional and seasonal effects on the gastrointestinal parasitism of captive forest musk deer.

PubMed

Hu, Xiao-Long; Liu, Gang; Wei, Yu-Ting; Wang, Yi-Hua; Zhang, Tian-Xiang; Yang, Shuang; Hu, De-Fu; Liu, Shu-Qiang

2018-01-01

Parasite infections can cause adverse effects on health, survival and welfare of forest musk deer. However, few studies have quantified the parasite infection status and evaluated the parasite temporal dynamics and differences between breeding centers for captive forest musk deer. The purpose of this study was to assess seasonal and regional effects on the parasite prevalence, shedding capacity, diversity, aggregation and infracommunity to establish baseline data on captive forest musk deer. The McMaster technique was applied to count parasite eggs or oocysts in 990 fecal samples collected at three breeding centers located in Qinling Mountains and Tibetan Plateau during spring, summer, and winter. Five gastrointestinal parasite groups were found in musk deer, and Eimeria spp. were dominant (mean oocysts per gram=1273.7±256.3). A positive correlation between Eimeria spp. and Strongyloides spp. (r=0.336, p<0.001) based on shedding capacity data was found, as well as a negative correlation between Eimeria spp. and Moniezia spp. (r=-0.375, p=0.003). Both seasonal and regional differences in diversity, prevalence, shedding capacity, aggregation and infracommunity were observed for five parasite groups. The low level of aggregation and high shedding capacity of Eimeria spp. and Strongyloides spp. might reflect the contaminated environment, and indicate that host-parasite relationships are unstable. The high degree of aggregation of Trichuris spp., Ascaris spp., and Moniezia spp. also suggests that some individual hosts had less ability to resist pathogens and greater transmission potential than others. These conclusions suggest that a focus on disease control strategies could improve the health of forest musk deer in captivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Multi-component determination of atmospheric semi-volatile organic compounds in soils and vegetation from Tarragona County, Catalonia, Spain.

PubMed

Domínguez-Morueco, Noelia; Carvalho, Mariana; Sierra, Jordi; Schuhmacher, Marta; Domingo, José Luis; Ratola, Nuno; Nadal, Martí

2018-08-01

Tarragona County (Spain) is home to the most important chemical/petrochemical industrial complex in Southern Europe, which raises concerns about the presence and effects of the numerous environmental contaminants. In order to assess the levels and patterns of five classes of semi-volatile organic compounds (SVOCs) - polycyclic aromatic hydrocarbons (PAHs), synthetic musks (SMs), polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs) and one organochlorine pesticide, hexachlorobenzene (HCB), 27 samples of soil and vegetation (Piptatherum L.) from different areas (petrochemical, chemical, urban/residential, and background) of Tarragona County were analysed. The results show that PAHs levels in soils ranged from 45.12 to 158.00ng/g and the urban areas presented the highest concentrations, mainly associated with the presence of a nearby highway and several roads with heavy traffic. PAHs levels in vegetation samples ranged from 42.13 to 80.08ng/g, where the greatest influence came from the urban and petrochemical areas. In the case of SMs, levels in soils and vegetation samples ranged from 5.42 to 10.04ng/g and from 4.08 to 17.94ng/g, respectively, and in both cases, background areas (at least 30km away from the main SVOCs emission sources) showed the highest levels, suggesting an influence of the personal care products derived from beach-related tourism in the coast. PCBs (from 6.62 to 14.07ng/g in soils; from 0.52 to 4.41ng/g in vegetation) prevailed in the chemical area in both matrices, probably associated with the presence of two sub-electrical stations located in the vicinities. In general terms, BFRs and HCB values recorded in soil and vegetation samples were quite similar between matrices and sampling areas. Copyright © 2018. Published by Elsevier B.V.

Proceedings of the International Symposium on Quantum Biology and Quantum Pharmacology (14th) Held in Marineland, Florida on March 12-14 1987. Annual Sanibel Symposia (27th). Part 1.

DTIC Science & Technology

1987-01-01

extension, though at a different rate. At the 6-31G** level, the C--O elon - gation in the three dimers is equal to 0.012 A and 0.014 A in the formic acid...will have vastly different counts of paths, even though they possess similar properties. An ex- ample is provided by civetone, a macrocyclic musk and a...sterol that possesses a de- cidedly musk -like odor as observed by Prelog and Ruicka [141. Both have a similar periphery and a similar musk odor, but

East-west genetic differentiation in Musk Ducks (Biziura lobata) of Australia suggests late Pleistocene divergence at the Nullarbor Plain

USGS Publications Warehouse

Guay, P.-J.; Chesser, R.T.; Mulder, R.A.; Afton, A.D.; Paton, D.C.; McCracken, K.G.

2010-01-01

Musk Ducks (Biziura lobata) are endemic to Australia and occur as two geographically isolated populations separated by the Nullarbor Plain, a vast arid region in southern Australia. We studied genetic variation in Musk Duck populations at coarse (eastern versus western Australia) and fine scales (four sites within eastern Australia). We found significant genetic structure between eastern and western Australia in the mtDNA control region (??ST = 0. 747), one nuclear intron (??ST = 0.193) and eight microsatellite loci (FST = 0.035). In contrast, there was little genetic structure between Kangaroo Island and adjacent mainland regions within eastern Australia. One small population of Musk Ducks in Victoria (Lake Wendouree) differed from both Kangaroo Island and the remainder of mainland eastern Australia, possibly due to genetic drift exacerbated by inbreeding and small population size. The observed low pairwise distance between the eastern and western mtDNA lineages (0.36%) suggests that they diverged near the end of the Pleistocene, a period characterised by frequent shifts between wet and arid conditions in central Australia. Our genetic results corroborate the display call divergence and Mathews' (Austral Avian Record 2:83-107, 1914) subspecies classification, and confirm that eastern and western populations of Musk Duck are currently isolated from each other. ?? 2010 Springer Science+Business Media B.V.

Determination of 24 personal care products in fish bile using hybrid solvent precipitation and dispersive solid phase extraction cleanup with ultrahigh performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry.

PubMed

Yao, Li; Lv, Yin-Zhi; Zhang, Li-Juan; Liu, Wang-Rong; Zhao, Jian-Liang; Liu, You-Sheng; Zhang, Qian-Qian; Ying, Guang-Guo

2018-05-25

Personal care products (PCPs) are ubiquitous in aquatic environments owing to the continuous discharge of domestic wastewater from highly urbanized regions. These PCPs can be adsorbed by fish and thereafter usually enter the bile of the fish through biliary excretion. In this study, a sensitive method based on a combination of hybrid solvent precipitation and dispersive solid phase extraction (d-SPE) purification was developed to simultaneously extract and detect 24 PCPs, namely, 16 biocides, 4 synthetic musks, and 4 benzotriazoles, from fish bile. Hybrid precipitation on solid phase extraction (SPE) tubes was applied to remove phospholipids and proteins, and a d-SPE procedure was used for further purification. The extraction solvents for the hybrid precipitation/SPE tubes and d-SPE materials were optimized. The method performance for bile samples both with and without enzyme hydrolysis using β-glucuronidase/aryl-sulfatase were validated. The 24 PCPs in fish bile were spiked with standard concentrations of 10 ng/mL, 20 ng/mL, 100 ng/mL, and 200 ng/mL to evaluate recoveries, which ranged from 70 to 120% for 16, 16, 22, and 21 analytes with hydrolysis, respectively, and 70-120% for 14, 15, 23, and 23 analytes without hydrolysis, respectively. The quantification limits for target PCPs were in the range 0.26-7.38 ng/mL [excluding musk xylene (MX) and musk ketone (MK)] and 0.20-9.48 ng/mL (excluding MX and MK) for bile samples with and without enzyme hydrolysis, respectively. After enzyme hydrolysis, 12 PCPs were detected in bile from fish collected from the Yangtze River, with a maximum detected concentration of 460 ng/mL, for triclosan (TCS). The hydrolysis reaction indicated that high percentages of glucuronide and sulfate metabolites for some PCPs, i.e. four parabens and TCS, existed in the bile. Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical contamination assessment in mangrove-lined Caribbean coastal systems using the oyster Crassostrea rhizophorae as biomonitor species.

PubMed

Aguirre-Rubí, Javier R; Luna-Acosta, Andrea; Etxebarría, Nestor; Soto, Manu; Espinoza, Félix; Ahrens, Michael J; Marigómez, Ionan

2018-05-01

This paper aims to contribute to the use of mangrove cupped oyster, Crassostrea rhizophorae, as a biomonitor species for chemical contamination assessment in mangrove-lined Caribbean coastal systems. Sampling was carried out in eight localities (three in Nicaragua and five in Colombia) with different types and levels of contamination. Oysters were collected during the rainy and dry seasons of 2012-2013 and the tissue concentrations of metals, polycyclic aromatic hydrocarbons (PAHs), and persistent organic pollutants (POPs) were determined. Low tissue concentrations of metals (except Hg) and PAHs; moderate-to-high tissue concentrations of Hg, hexachlorocyclohexanes (HCHs), and dichlorodiphenyl-trichloroethanes (DDTs); detectable levels of chlorpyrifos, polychlorinated biphenyls (PCBs) (mainly CB28, CB118, CB138 and CB 153) and brominated diphenyl ethers 85 (BDE85); and negligible levels of musks were recorded in Nicaraguan oysters. A distinct profile of POPs was identified in Colombia, where the tissue concentrations of PCBs and synthetic musk fragrances were low to moderate, and Ag, As, Cd, Pb, and PAHs ranged from moderate to extremely high. Overall, the values recorded for HCHs, DDTs and PCBs in Nicaraguan mangrove cupped oysters greatly exceeded the reference values in tissues of C. rhizophorae from the Wider Caribbean Region, whereas only the levels of PCBs were occasionally surpassed in Colombia. Different contaminant profiles were distinguished between oysters from Nicaragua and Colombia in radar plots constructed using the main groups of contaminants (metals, PAHs, musks, PCBs, and organochlorine pesticides (OCPs)). Likewise, integrated pollution indices revealed differences in the levels of contaminants. Moreover, the profiles and levels in oyster tissues also varied with season. Thus, principal component analysis clearly discriminated Nicaraguan and Colombian localities and, especially in Colombia, seasonal trends in chemical contamination and differences amongst localities were evidenced. The geographical and environmental disparity of the studied scenarios may represent to a large extent the diversity of mangrove-lined Caribbean coastal systems and therefore the present results support the use of C. rhizophorae as suitable biomonitor species at Caribbean regional scale, where seasonal variability is a major factor controlling pollutant mobility and bioavailability.

Recombination and selection in the major histocompatibility complex of the endangered forest musk deer (Moschus berezovskii).

PubMed

Cai, Ruibo; Shafer, Aaron B A; Laguardia, Alice; Lin, Zhenzhen; Liu, Shuqiang; Hu, Defu

2015-11-25

The forest musk deer (Moschus berezovskii) is a high elevation species distributed across western China and northern Vietnam. Once abundant, habitat loss and poaching has led to a dramatic decrease in population numbers prompting the IUCN to list the species as endangered. Here, we characterized the genetic diversity of a Major Histocompatibility Complex (MHC) locus and teased apart driving factors shaping its variation. Seven DRB exon 2 alleles were identified among a group of randomly sampled forest musk deer from a captive population in the Sichuan province of China. Compared to other endangered or captive ungulates, forest musk deer have relatively low levels of MHC genetic diversity. Non-synonymous substitutions primarily occurred in the putative peptide-binding region (PBR), with analyses suggesting that recombination and selection has shaped the genetic diversity across the locus. Specifically, inter-allelic recombination generated novel allelic combinations, with evidence for both positive selection acting on the PBR and negative selection on the non-PBR. An improved understanding of functional genetic variability of the MHC will facilitate better design and management of captive breeding programs for this endangered species.

HnRNP C, YB-1 and hnRNP L coordinately enhance skipping of human MUSK exon 10 to generate a Wnt-insensitive MuSK isoform

PubMed Central

Nasrin, Farhana; Rahman, Mohammad Alinoor; Masuda, Akio; Ohe, Kenji; Takeda, Jun-ichi; Ohno, Kinji

2014-01-01

Muscle specific receptor tyrosine kinase (MuSK) is an essential postsynaptic transmembrane molecule that mediates clustering of acetylcholine receptors (AChR). MUSK exon 10 is alternatively skipped in human, but not in mouse. Skipping of this exon disrupts a cysteine-rich region (Fz-CRD), which is essential for Wnt-mediated AChR clustering. To investigate the underlying mechanisms of alternative splicing, we exploited block-scanning mutagenesis with human minigene and identified a 20-nucleotide block that contained exonic splicing silencers. Using RNA-affinity purification, mass spectrometry, and Western blotting, we identified that hnRNP C, YB-1 and hnRNP L are bound to MUSK exon 10. siRNA-mediated knockdown and cDNA overexpression confirmed the additive, as well as the independent, splicing suppressing effects of hnRNP C, YB-1 and hnRNP L. Antibody-mediated in vitro protein depletion and scanning mutagenesis additionally revealed that binding of hnRNP C to RNA subsequently promotes binding of YB-1 and hnRNP L to the immediate downstream sites and enhances exon skipping. Simultaneous tethering of two splicing trans-factors to the target confirmed the cooperative effect of YB-1 and hnRNP L on hnRNP C-mediated exon skipping. Search for a similar motif in the human genome revealed nine alternative exons that were individually or coordinately regulated by hnRNP C and YB-1. PMID:25354590

Organization of the main olfactory bulbs of some mammals: musk shrews, moles, hedgehogs, tree shrews, bats, mice, and rats.

PubMed

Kosaka, Katsuko; Kosaka, Toshio

2004-04-19

We immunohistochemically examined the organization of the main olfactory bulbs (MOBs) in seven mammalian species, including moles, hedgehogs, tree shrews, bats, and mice as well as laboratory musk shrews and rats. We focused our investigation on two points: 1) whether nidi, particular spheroidal synaptic regions subjacent to glomeruli, which we previously reported for the laboratory musk shrew MOBs, are also present in other animals and 2) whether the compartmental organization of glomeruli and two types of periglomerular cells we proposed for the rat MOBs are general in other animals. The general laminar pattern was similar among these seven species, but discrete nidi and the nidal layer were recognized only in two insectivores, namely, the mole and laboratory musk shrew. Olfactory marker protein-immunoreactive (OMP-IR) axons extended beyond the limits of the glomerular layer (GL) into the superficial region of the external plexiform layer (EPL) or the nidal layer in the laboratory musk shrew, mole, hedgehog, and tree shrew but not in bat, mouse, and rat. We observed, in nidi and the nidal layer in the mole and laboratory musk shrew MOBs, only a few OMP-IR axons. In the hedgehog, another insectivore, OMP-IR processes extending from the glomeruli were scattered and intermingled with calbindin D28k-IR cells at the border between the GL and the EPL. In the superficial region of the EPL of the tree shrew MOBs, there were a small number of tiny glomerulus-like spheroidal structures where OMP-IR axons protruding from glomeruli were intermingled with dendritic branches of surrounding calbindin D28k-IR cells. Furthermore, we recognized the compartmental organization of glomeruli and two types of periglomerular cells in the MOBs of all of the mammals we examined. These structural features are therefore considered to be common and important organizational principles of the MOBs. Copyright 2004 Wiley-Liss, Inc.

DETERMINATION OF A BOUND MUSK XYLENE METABOLITE IN CARP HEMOGLOBIN AS A BIOMARKER OF EXPOSURE BY GAS CHROMATOGRAPHY MASS SPECTROMETRY USING SELECTED ION MONITORING

EPA Science Inventory

Musk xylene (MX) is widely used as a fragrance ingredient in commercial toiletries. Identification and quantification of a bound 4-amino-MX (AMX) metabolite was carried out by gas chromatography-mass spectrometry (GC/MS), with selected ion monitoring (SIM). Detection of AMX occur...

Effects of Ethnic Settlements and Land Management Status on Species Distribution Patterns: A Case Study of Endangered Musk Deer (Moschus spp.) in Northwest Yunnan, China.

PubMed

Li, Xueyou; Bleisch, William V; Jiang, Xuelong

2016-01-01

Understanding the status and spatial distribution of endangered species in biologically and ethnologically diverse areas is important to address correlates of cultural and biological diversity. We developed models for endangered musk deer (Moschus spp.) abundance indices in and around protected areas inhabited by different ethnic groups in northwest Yunnan China to address different anthropogenic and management-related questions. We found that prediction of relative abundance of musk deer was best accomplished using ethnicity of settlements, conservation status and poaching pressure in an area. Musk deer were around 5 times more abundant in Tibetan regions relative to Lisu regions. We found no significant negative correlates of gathering and transhumance activities on musk deer abundance. Hunting pressure showed no significant differences between protected and non-protected areas, but showed significant differences among ethnic groups. Hunting pressures in areas adjacent to Lisu settlements was 7.1 times more than in areas adjacent to Tibetan settlements. Our findings indicate protected areas in southwest China are not fully effective in deterring human disturbance caused by traditional practices. We suggest that conservation and management strategies should engage traditional culture and practices with a positive conservation impact. Better understanding of indigenous culture may open up new opportunities for species conservation in much wider tracts of unprotected and human-dominated lands. Traditional practices that are not destructive to biodiversity should be allowed as a way of providing a link between the local communities and protected areas thereby creating incentives for conservation.

Fatal pneumonia epizootic in musk ox (Ovibos moschatus) in a period of extraordinary weather conditions.

PubMed

Ytrehus, Bjørnar; Bretten, Tord; Bergsjø, Bjarne; Isaksen, Ketil

2008-06-01

The musk ox is adapted to extreme cold and regarded as vulnerable to the impacts of climate change. Population decline is proposed to occur due to changes in forage availability, insect harassment, parasite load, and habitat availability, while the possible role of infectious diseases has not been emphasized. The goal of the present article is to describe an outbreak of fatal pasteurellosis that occurred in the introduced musk ox population of Dovrefjell, Norway in 2006, causing the death of a large proportion of the animals. The epizootic coincided with extraordinary warm and humid weather, conditions that often are associated with outbreaks of pasteurellosis. The description is based on long series of data from the surveillance of the musk ox population, weather data from a closely located meteorological station, and pathoanatomical investigation of the diseased animals. It is concluded that the weather conditions likely were the decisive factors for the outbreak. It is suggested that such epizootics may occur increasingly among cold-adapted animals if global warming results in increased occurrence of heat waves and associated extreme weather events, thereby causing population declines and possibly extinctions.

Structural basis of agrin-LRP4-MuSK signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zong, Yinong; Zhang, Bin; Gu, Shenyan

Synapses are the fundamental units of neural circuits that enable complex behaviors. The neuromuscular junction (NMJ), a synapse formed between a motoneuron and a muscle fiber, has contributed greatly to understanding of the general principles of synaptogenesis as well as of neuromuscular disorders. NMJ formation requires neural agrin, a motoneuron-derived protein, which interacts with LRP4 (low-density lipoprotein receptor-related protein 4) to activate the receptor tyrosine kinase MuSK (muscle-specific kinase). However, little is known of how signals are transduced from agrin to MuSK. Here, we present the first crystal structure of an agrin-LRP4 complex, consisting of two agrin-LRP4 heterodimers. Formation ofmore » the initial binary complex requires the z8 loop that is specifically present in neuronal, but not muscle, agrin and that promotes the synergistic formation of the tetramer through two additional interfaces. We show that the tetrameric complex is essential for neuronal agrin-induced acetylcholine receptor (AChR) clustering. Collectively, these results provide new insight into the agrin-LRP4-MuSK signaling cascade and NMJ formation and represent a novel mechanism for activation of receptor tyrosine kinases.« less

Field dissipation and risk assessment of typical personal care products TCC, TCS, AHTN and HHCB in biosolid-amended soils.

PubMed

Chen, Feng; Ying, Guang-Guo; Ma, Yi-Bing; Chen, Zhi-Feng; Lai, Hua-Jie; Peng, Feng-Jiao

2014-02-01

The antimicrobial agents triclocarban (TCC) and triclosan (TCS) and synthetic musks AHTN (Tonalide) and HHCB (Galaxolide) are widely used in many personal care products. These compounds may release into the soil environment through biosolid application to agricultural land and potentially affect soil organisms. This paper aimed to investigate accumulation, dissipation and potential risks of TCC, TCS, AHTN and HHCB in biosolid-amended soils of the three field trial sites (Zhejiang, Hunan and Shandong) with three treatments (CK: control without biosolid application, T1: single biosolid application, T2: repeated biosolid application every year). The one-year monitoring results showed that biosolids application could lead to accumulation of these four chemicals in the biosolid-amended soils, with the residual concentrations in the following order: TCC>TCS>AHTN>HHCB. Dissipation of TCC, TCS, AHTN and HHCB in the biosolid-amended soils followed the first-order kinetics model. Half-lives for TCC, TCS, AHTN and HHCB under the field conditions of Shandong site were 191, 258, 336 and 900 days for T1, and 51, 106, 159 and 83 days for T2, respectively. Repeated applications of biosolid led to accumulation of these personal care products and result in higher ecological risks. Based on the residual levels in the trial sites and limited toxicity data, high risks to soil organisms are expected for TCC and TCS, while low-medium risks for AHTN and HHCB. © 2013.

Archaeological Salvage Excavations at the Tibbee Creek Site (22Lo600) Lowndes County, Mississippi.

DTIC Science & Technology

1981-06-01

Kinosternon subrubrum musk turtle Sternotherus sp. musk turtle Chyemys sp. pond turtle Trionyx sp. soft shelled turtle Fish Amia calva bowfin Lepisosteus sp...OSTEICHTHIES Amia calva - 1 pharyngeal mouth piece Scianidae (possibly Aplodinotus grunniens) - 2 teeth Osteichthies - (possibly catostomidae...Unidentified bird - 1 shaft fragment OSTEICHTHIES Amia calva - skull fragment Amia calva (?) - pharyngeal mouth fragment Micropterus sp. - 1 pharyngeal mouth

Novel pollutants in the Moscow atmosphere in winter period: Gas chromatography-high resolution time-of-flight mass spectrometry study.

PubMed

Mazur, D M; Polyakova, O V; Artaev, V B; Lebedev, A T

2017-03-01

The most common mass spectrometry approach analyzing contamination of the environment deals with targeted analysis, i.e. detection and quantification of the selected (priority) pollutants. However non-targeted analysis is becoming more often the method of choice for environmental chemists. It involves implementation of modern analytical instrumentation allowing for comprehensive detection and identification of the wide variety of compounds of the environmental interest present in the sample, such as pharmaceuticals and their metabolites, musks, nanomaterials, perfluorinated compounds, hormones, disinfection by-products, flame retardants, personal care products, and many others emerging contaminants. The paper presents the results of detection and identification of previously unreported organic compounds in snow samples collected in Moscow in March 2016. The snow analysis allows evaluation of long-term air pollution in the winter period. Gas chromatography coupled to a high resolution time-of-flight mass spectrometer has enabled us with capability to detect and identify such novel analytes as iodinated compounds, polychlorinated anisoles and even Ni-containing organic complex, which are unexpected in environmental samples. Some considerations concerning the possible sources of origin of these compounds in the environment are discussed. Copyright © 2017 LECO. Published by Elsevier Ltd.. All rights reserved.

LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner

PubMed Central

Ohkawara, Bisei; Cabrera-Serrano, Macarena; Nakata, Tomohiko; Milone, Margherita; Asai, Nobuyuki; Ito, Kenyu; Ito, Mikako; Masuda, Akio; Ito, Yasutomo; Engel, Andrew G.; Ohno, Kinji

2014-01-01

Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Using Sanger and exome sequencing in a CMS patient, we identified two heteroallelic mutations, p.Glu1233Lys and p.Arg1277His, in LRP4 coding for the postsynaptic low-density lipoprotein receptor-related protein 4. LRP4, expressed on the surface of the postsynaptic membrane of the neuromuscular junction, is a receptor for neurally secreted agrin, and LRP4 bound by agrin activates MuSK. Activated MuSK in concert with Dok-7 stimulates rapsyn to concentrate and anchor AChR on the postsynaptic membrane and interacts with other proteins implicated in the assembly and maintenance of the neuromuscular junction. LRP4 also functions as an inhibitor of Wnt/beta-catenin signaling. The identified mutations in LRP4 are located at the edge of its 3rd beta-propeller domain and decrease binding affinity of LRP4 for both MuSK and agrin. Mutations in the LRP4 3rd beta-propeller domain were previously reported to impair Wnt signaling and cause bone diseases including Cenani–Lenz syndactyly syndrome and sclerosteosis-2. By analyzing naturally occurring and artificially introduced mutations in the LRP4 3rd beta-propeller domain, we show that the edge of the domain regulates the MuSK signaling whereas its central cavity governs Wnt signaling. We conclude that LRP4 is a new CMS disease gene and that the 3rd beta propeller domain of LRP4 mediates the two signaling pathways in a position-specific manner. PMID:24234652

Occurrence, profile and spatial distribution of UV-filters and musk fragrances in mussels from Portuguese coastline.

PubMed

Castro, M; Fernandes, J O; Pena, A; Cunha, S C

2018-07-01

The increasing production and consumption of Personal Care Products (PCPs), containing UV-filters and musk fragrances, has led to its widespread presence in the aquatic environment which can cause harmful effects to the aquatic organisms due to its intrinsic toxicity. This study aims to evaluate the degree of contamination of wild mussels along the entire Portuguese coastline, continually exposed in their habitat to different contaminants. For this purpose, approximately 1000 mussel specimens were sampled during one year in seven different locations, along the Portuguese coastline. Simultaneous quantification of five UV-filters and seven musks in mussels was achieved by a Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) extraction procedure combined with dispersive liquid-liquid microextraction (DLLME) followed by gas chromatography with mass spectrometry (GC-MS) analysis. Ten out of the twelve target analytes were found in the analysed samples, highlighting the presence of AHTN (tonalide), EHS (2-ethylhexylsalicylate) and EHMC (2-ethylhexyl 4-methoxycinnamate) in all positive samples (93%). Overall, the results obtained indicate a widespread contamination of wild mussels along Portuguese coastline, all over the year. UV-filters were more frequently detected (90%) than musk fragrances (70%) and also quantified at higher levels, with average total concentrations reaching 1155.8 ng/g (dw) against 397.7 ng/g (dw) respectively. A high correlation was observed between the most densely populated and industrialized locations and the higher levels of musks and UV-filters found. In other hand, lower levels of PCPs were found in protected areas. As expected, an increase in UV-filters levels was observed after the summer, likely due to the intense period of recreational activities. Copyright © 2018 Elsevier Ltd. All rights reserved.

Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews

PubMed Central

Meyers, Kelly; Lim, Audrey; Dye, Matthew; Pak, Diana; Rinaman, Linda; Yates, Bill J.

2014-01-01

Signals from the vestibular system, area postrema, and forebrain elicit nausea and vomiting, but gastrointestinal (GI) vagal afferent input arguably plays the most prominent role in defense against food poisoning. It is difficult to determine the contribution of GI vagal afferent input on emesis because various agents (e.g., chemotherapy) often act on multiple sensory pathways. Intragastric copper sulfate (CuSO4) potentially provides a specific vagal emetic stimulus, but its actions are not well defined in musk shrews (Suncus murinus), a primary small animal model used to study emesis. The aims of the current study were 1) to investigate the effects of subdiaphragmatic vagotomy on CuSO4-induced emesis and 2) to conduct preliminary transneuronal tracing of the GI-brain pathways in musk shrews. Vagotomy failed to inhibit the number of emetic episodes produced by optimal emetic doses of CuSO4 (60 and 120 mg/kg ig), but the effects of lower doses were dependent on an intact vagus (20 and 40 mg/kg). Vagotomy also failed to affect emesis produced by motion (1 Hz, 10 min) or nicotine administration (5 mg/kg sc). Anterograde transport of the H129 strain of herpes simplex virus-1 from the ventral stomach wall identified the following brain regions as receiving inputs from vagal afferents: the nucleus of the solitary tract, area postrema, and lateral parabrachial nucleus. These data indicate that the contribution of vagal pathways to intragastric CuSO4-induced emesis is dose dependent in musk shrews. Furthermore, the current neural tracing data suggest brain stem anatomical circuits that are activated by GI signaling in the musk shrew. PMID:24430885

Review of 'emerging' organic contaminants in biosolids and assessment of international research priorities for the agricultural use of biosolids.

PubMed

Clarke, Bradley O; Smith, Stephen R

2011-01-01

A broad spectrum of organic chemicals is essential to modern society. Once discharged from industrial, domestic and urban sources into the urban wastewater collection system they may transfer to the residual solids during wastewater treatment and assessment of their significance and implications for beneficial recycling of the treated sewage sludge biosolids is required. Research on organic contaminants (OCs) in biosolids has been undertaken for over thirty years and the increasing body of evidence demonstrates that the majority of compounds studied do not place human health at risk when biosolids are recycled to farmland. However, there are 143,000 chemicals registered in the European Union for industrial use and all could be potentially found in biosolids. Therefore, a literature review of 'emerging' OCs in biosolids has been conducted for a selection of chemicals of potential concern for land application based upon human toxicity, evidence of adverse effects on the environment and endocrine disruption. To identify monitoring and research priorities the selected chemicals were ranked using an assessment matrix approach. Compounds were evaluated based upon environmental persistence, human toxicity, evidence of bioaccumulation in humans and the environment, evidence of ecotoxicity and the number and quality of studies focussed on the contaminant internationally. The identified chemicals of concern were ranked in decreasing order of priority: perfluorinated chemicals (PFOS, PFOA); polychlorinated alkanes (PCAs), polychlorinated naphthalenes (PCNs); organotins (OTs), polybrominated diphenyl ethers (PBDEs), triclosan (TCS), triclocarban (TCC); benzothiazoles; antibiotics and pharmaceuticals; synthetic musks; bisphenol A, quaternary ammonium compounds (QACs), steroids; phthalate acid esters (PAEs) and polydimethylsiloxanes (PDMSs). A number of issues were identified and recommendations for the prioritisation of further research and monitoring of 'emerging' OCs for the agricultural use of biosolids are provided. In particular, a number of 'emerging' OCs (PFOS, PFOA and PCAs) were identified for priority attention that are environmentally persistent and potentially toxic with unique chemical properties, or are present in large concentrations in sludge, that make it theoretically possible for them to enter human and ecological food-chains from biosolids-amended soil. Copyright © 2010 Elsevier Ltd. All rights reserved.

Estimation of body surface area in the musk shrew ( Suncus murinus): a small animal for testing chemotherapy-induced emesis.

PubMed

Eiseman, Julie L; Sciullo, Michael; Wang, Hong; Beumer, Jan H; Horn, Charles C

2017-10-01

Several cancer chemotherapies cause nausea and vomiting, which can be dose-limiting. Musk shrews are used as preclinical models for chemotherapy-induced emesis and for antiemetic effectiveness. Unlike rats and mice, shrews possess a vomiting reflex and demonstrate an emetic profile similar to humans, including acute and delayed phases. As with most animals, dosing of shrews is based on body weight, while translation of such doses to clinically equivalent exposure requires doses based on body surface area. In the current study body surface area in musk shrews was directly assessed to determine the Meeh constant (K m ) conversion factor (female = 9.97, male = 9.10), allowing estimation of body surface area based on body weight. These parameters can be used to determine dosing strategies for shrew studies that model human drug exposures, particularly for investigating the emetic liability of cancer chemotherapeutic agents.

Monitoring contaminants of emerging concern from tertiary wastewater treatment plants using passive sampling modelled with performance reference compounds.

PubMed

Sultana, Tamanna; Murray, Craig; Ehsanul Hoque, M; Metcalfe, Chris D

2016-12-01

The Lake Simcoe watershed in Ontario, Canada is an important recreational area and a recharge zone for groundwater resources. Lake Simcoe is a relatively shallow lotic system that has been impacted by urban development, recreation, industry and agriculture. As part of a watershed management plan, six wastewater treatment plants (WWTPs) located in this catchment basin were selected to measure the inputs of contaminants of emerging concern (CECs) of wastewater origin. These WWTPs were recently upgraded to tertiary treatment for phosphorus removal. Polar organic chemical integrative samplers (POCIS) and semipermeable membrane devices (SPMDs) were used to monitor for hydrophilic and hydrophobic CECs, respectively, in treated and untreated wastewater. The passive samplers were calibrated with performance reference compounds (PRCs) by measuring the loss of deuterated beta blocker drugs spiked into POCIS and the loss of PCB congeners spiked into SPMDs over the course of 14-day deployment periods. From the PRC data, field sampling rates of CECs were determined and applied to estimate time-weighted average (TWA) concentrations and mass loadings in mg/day/1000 members of the population serviced. In treated wastewater, TWA concentrations of an antibiotic, sulfamethoxazole, the prescription drugs, carbamazepine, naproxen and gemfibrozil, and the non-prescription drug, ibuprofen, were estimated to be in the low (<18 ng/L) range. The artificial sweeteners, sucralose and acesulfame, were particularly useful chemical tracers, with estimated TWA concentrations in treated wastewater ranging from 128 to 213 ng/L and 4 to 33 ng/L, respectively. The steroid hormones were detected only rarely in treated wastewater. Triclosan, triclocarban and the synthetic musks, HHCB and AHTN, were removed efficiently (>77 %), possibly because of the tertiary treatment technologies. Therefore, the mass loadings for these personal care products were all <5 mg/day/1000 people. Overall, this study indicates that tertiary treatment technologies designed for phosphorus removal do not entirely remove the target CECs.

The use of monitoring data in EU chemicals management--experiences and considerations from the German environmental specimen bank.

PubMed

Koschorreck, Jan; Heiss, Christiane; Wellmitz, Jörg; Fliedner, Annette; Rüdel, Heinz

2015-02-01

Since the 1970s, environmental specimen banks (ESB) have emerged in many countries. Their highly standardised sampling and archiving strategies make them a valuable tool in tracing time trends and spatial distributions of chemicals in ecosystem compartments. The present article intends to highlight the potential of ESBs for regulatory agencies in the European Union (EU). The arguments are supported by examples of retrospective monitoring studies conducted under the programme of the German ESB. These studies have evaluated the success of regulatory and industry provisions for substances of concern (i.e. PCB, polybrominated diphenyl ethers, perfluorinated compounds, alkylphenol compounds, organotin compounds, triclosan/methyl-triclosan, musk fragrances). Time trend studies revealed for example that levels of organotin compounds in marine biota from German coastal waters decreased significantly after the EU had decided on a total ban of organotin-based antifoulings in 2003. Similarly, concentrations of commercially relevant congeners of polybrominated diphenyl ethers decreased in herring gull eggs from the North Sea only after an EU-wide ban in 2004. The data presented demonstrate the usefulness of ESB samples for (retrospective) time trend monitoring and underline the benefit of a more intensive cooperation between chemicals management and specimen banking.

Origin of inorganic and organic components of PM2.5 in subway stations of Barcelona, Spain.

PubMed

Martins, Vânia; Moreno, Teresa; Minguillón, María Cruz; van Drooge, Barend L; Reche, Cristina; Amato, Fulvio; de Miguel, Eladio; Capdevila, Marta; Centelles, Sonia; Querol, Xavier

2016-01-01

The present work assesses indoor air quality in stations of the Barcelona subway system. PM2.5 concentrations on the platforms of 4 subway stations were measured during two different seasons and the chemical composition was determined. A Positive Matrix Factorization analysis was performed to identify and quantify the contributions of major PM2.5 sources in the subway stations. Mean PM2.5 concentrations varied according to the stations design and seasonal periods. PM2.5 was composed of haematite, carbonaceous aerosol, crustal matter, secondary inorganic compounds, trace elements, insoluble sulphate and halite. Organic compounds such as PAHs, nicotine, levoglucosan and aromatic musk compounds were also identified. Subway PM2.5 source comprised emissions from rails, wheels, catenaries, brake pads and pantographs. The subway source showed different chemical profiles for each station, but was always dominated by Fe. Control actions on the source are important for the achievement of better air quality in the subway environment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mild aerobic training with blood flow restriction increases the hypertrophy index and MuSK in both slow and fast muscles of old rats: Role of PGC-1α.

PubMed

Bahreinipour, Mohammad-Ali; Joukar, Siyavash; Hovanloo, Fariborz; Najafipour, Hamid; Naderi, Vida; Rajiamirhasani, Alireza; Esmaeili-Mahani, Saeed

2018-06-01

Existing evidence emphasize the role of mitochondrial dysfunction in sarcopenia which is revealed as loss of skeletal muscle mass and neuromuscular junction remodeling. We assessed the effect of low-intensity aerobic training along with blood flow restriction on muscle hypertrophy index, muscle-specific kinase (MuSK), a pivotal protein of the neuromuscular junction and Peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) in aged male rats. Animals groups were control (CTL), sham (Sh), leg blood flow restriction (BFR), exercise (Ex), sham + exercise (Sh + Ex), and BFR plus exercise (BFR + Ex) groups. The exercise groups were trained with low intensity exercise for 10 weeks. 48 h after the last training session, animals were sacrificed under anesthesia. Soleus and EDL muscles were isolated, hypertrophy index was estimated and MuSK and PGC-1α were measured by western blot method. Hypertrophy index enhanced in soleus and Extensor digitorum longus (EDL) muscles of BFR + Ex group (P < 0.01 versus CTL and Sh groups, and P < 0.001 versus other groups). The MuSK protein of soleus and EDL muscles increased in BFR + Ex group (P < 0.01 and P < 0.001, respectively) in comparison with CTL and Sh groups. In BFR + Ex group, the PGC-1α protein increased in both soleus and EDL (P < 0.001 compared to other groups). Also the PGC-1α of soleus muscle was higher in Ex and Sh + Ex groups versus CTL and Sh groups (P < 0.05). Findings suggest that low endurance exercise plus BFR improves the MuSK and hypertrophy index of both slow and fast muscles of elderly rats probably through the rise of PGC-1α expression. Copyright © 2018. Published by Elsevier Inc.

Quality Assurance of Current Combat Ration Pack Components: 12 Months Progress Report on 2010/11 Ration Packing Program

DTIC Science & Technology

2013-04-01

Cream of Chicken Soup, Marmalade, Orange Sports Powder, Grape Sports Powder, Banana Berry Candy, Musk Candy, Tomato Ketchup and Sweet Chilli Sauce...Strong Peppermint (ESP) Candy............................................... 19 3.8.3 Banana Berry Candy...M M Marmalade P P P M AR Plum Fruit Spread P P P P P Strawberry Fruit Spread P M P P P P Chocolate Candy M Banana Berry Candy P M M M M P AR Musk

Anti-MuSK myasthenia gravis presenting with Epstein-Barr virus-associated mononucleosis and immune-mediated diabetes mellitus.

PubMed

Bhibhatbhan, Arunee; Kline, Gregory; Vincent, Angela; Toth, Cory

2007-08-01

We report a young woman with the abrupt onset of infectious mononucleosis due to Epstein-Barr virus associated with a subsequent autoimmune form of diabetes mellitus and myasthenia gravis with anti-muscle-specific kinase (MuSK) antibodies. The simultaneous onset of these two autoimmune diseases preceded by a systemic viral illness supports a causal relationship between MuSK antibodies and myasthenia gravis and suggests the possibility of a viral trigger in some cases.

SpaceX Dragon Cargo Transfer

NASA Image and Video Library

2012-06-13

NASA Administrator Charles Bolden, left, congratulates SpaceX CEO and Chief Designer Elon Musk in front of the historic Dragon capsule that returned to Earth on May 31 following the first successful mission by a private company to carry supplies to the International Space Station on Wednesday, June 13, 2012 at the SpaceX facility in McGregor, Texas. Bolden and Musk also thanked the more than 150 SpaceX employees working at the McGregor facility for their role in the historic mission. Photo Credit: (NASA/Bill Ingalls)

SpaceX Dragon Cargo Transfer

NASA Image and Video Library

2012-06-13

NASA Administrator Charles Bolden, left, and SpaceX CEO and Chief Designer Elon Musk, view the historic Dragon capsule that returned to Earth on May 31 following the first successful mission by a private company to carry supplies to the International Space Station on Wednesday, June 13, 2012 at the SpaceX facility in McGregor, Texas. Bolden and Musk also thanked the more than 150 SpaceX employees working at the McGregor facility for their role in the historic mission. Photo Credit: (NASA/Bill Ingalls)

Analysis of Parent Synthetic Cannabinoids in Blood and Urinary Metabolites by Liquid Chromatography Tandem Mass Spectrometry

PubMed Central

Knittel, Jessica L.; Holler, Justin M.; Chmiel, Jeffrey D.; Vorce, Shawn P.; Magluilo, Joseph; Levine, Barry; Ramos, Gerardo; Bosy, Thomas Z.

2016-01-01

Synthetic cannabinoids emerged on the designer drug market in recent years due to their ability to produce cannabis-like effects without the risk of detection by traditional drug testing techniques such as immunoassay and gas chromatography–mass spectrometry. As government agencies work to schedule existing synthetic cannabinoids, new, unregulated and structurally diverse compounds continue to be developed and sold. Synthetic cannabinoids undergo extensive metabolic conversion. Consequently, both blood and urine specimens may play an important role in the forensic analysis of synthetic cannabinoids. It has been observed that structurally similar synthetic cannabinoids follow common metabolic pathways, which often produce metabolites with similar metabolic transformations. Presented are two validated quantitative methods for extracting and identifying 15 parent synthetic cannabinoids in blood, 17 synthetic cannabinoid metabolites in urine and the qualitative identification of 2 additional parent compounds. The linear range for most synthetic cannabinoid compounds monitored was 0.1–10 ng/mL with the limit of detection between 0.01 and 0.5 ng/mL. Selectivity, specificity, accuracy, precision, recovery and matrix effect were also examined and determined to be acceptable for each compound. The validated methods were used to analyze a compilation of synthetic cannabinoid investigative cases where both blood and urine specimens were submitted. The study suggests a strong correlation between the metabolites detected in urine and the parent compounds found in blood. PMID:26792810

Multi-residue analysis of legacy POPs and emerging organic contaminants in Singapore's coastal waters using gas chromatography-triple quadrupole tandem mass spectrometry.

PubMed

Zhang, Hui; Bayen, Stéphane; Kelly, Barry C

2015-08-01

A gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) based method was developed for determination of 86 hydrophobic organic compounds in seawater. Solid-phase extraction (SPE) was employed for sequestration of target analytes in the dissolved phase. Ultrasound assisted extraction (UAE) and florisil chromatography were utilized for determination of concentrations in suspended sediments (particulate phase). The target compounds included multi-class hydrophobic contaminants with a wide range of physical-chemical properties. This list includes several polycyclic and nitro-aromatic musks, brominated and chlorinated flame retardants, methyl triclosan, chlorobenzenes, organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). Spiked MilliQ water and seawater samples were used to evaluate the method performance. Analyte recoveries were generally good, with the exception of some of the more volatile target analytes (chlorobenzenes and bromobenzenes). The method is very sensitive, with method detection limits typically in the low parts per quadrillion (ppq) range. Analysis of 51 field-collected seawater samples (dissolved and particulate-bound phases) from four distinct coastal sites around Singapore showed trace detection of several polychlorinated biphenyl congeners and other legacy POPs, as well as several current-use emerging organic contaminants (EOCs). Polycyclic and nitro-aromatic musks, bromobenzenes, dechlorane plus isomers (syn-DP, anti-DP) and methyl triclosan were frequently detected at appreciable levels (2-20,000pgL(-1)). The observed concentrations of the monitored contaminants in Singapore's marine environment were generally comparable to previously reported levels in other coastal marine systems. To our knowledge, these are the first measurements of these emerging contaminants of concern in Singapore or Southeast Asia. The developed method may prove beneficial for future environmental monitoring of hydrophobic organic contaminants in marine environments. Further, the study provides novel information regarding several potentially hazardous contaminants of concern in Singapore's marine environment, which will aid future risk assessment initiatives. Copyright © 2015 Elsevier B.V. All rights reserved.

EXPEDITIOUS SYNTHETIC TRANSFORMATIONS USING MICROWAVES

EPA Science Inventory

Microwave-expedited solvent-free synthetic processes will be described for the synthesis of a variety of industrially significant compounds and intermediates namely, enamines, nitroalkenes, enones, oxidized sulfur compounds and ionic liquids. This solvent-free synthetic methodolo...

Antifungal and Antiaflatoxigenic Methylenedioxy-Containing Compounds and Piperine-Like Synthetic Compounds

PubMed Central

Moon, Young-Sun; Choi, Won-Sik; Park, Eun-Sil; Bae, In Kyung; Choi, Sung-Deuk; Paek, Ockjin; Kim, Sheen-Hee; Chun, Hyang Sook; Lee, Sung-Eun

2016-01-01

Twelve methylenedioxy-containing compounds including piperine and 10 piperine-like synthetic compounds were assessed to determine their antifungal and antiaflatoxigenic activities against Aspergillus flavus ATCC 22546 in terms of their structure–activity relationships. Piperonal and 1,3-benzodioxole had inhibitory effects against A. flavus mycelial growth and aflatoxin B1 production up to a concentration of 1000 μg/mL. Ten piperine-like synthetic compounds were synthesized that differed in terms of the carbon length in the hydrocarbon backbone and the presence of the methylenedioxy moiety. In particular, 1-(2-methylpiperidin-1-yl)-3-phenylprop-2-en-1-one had potent antifungal and antiaflatoxigenic effects against A. flavus up to a concentration of 1 μg/mL. This synthetic compound was remarkable because the positive control thiabendazole had no inhibitory effect at this concentration. Reverse transcription-PCR analysis showed that five genes involved in aflatoxin biosynthesis pathways were down-regulated in A. flavus, i.e., aflD, aflK, aflQ, aflR, and aflS; therefore, the synthetic compound inhibited aflatoxin production by down-regulating these genes. PMID:27537912

NITRO MUSK ADDUCTS OF RAINBOW TROUT ...

EPA Pesticide Factsheets

Rainbow trout and other fish species can serve as 'sentinel' species for the assessment of ecological status and the presence of certain environmental contaminants. As such they act as bioindicators of exposure. Here we present seminal data regarding dose-response and toxicokinetics of trout hemoglobin adduct formation from exposure to nitro musks that are frequently used as fragrance ingredients in formulations of personal care products. Hemoglobin adducts serve as biomarkers of exposure of the sentinel species as we have shown in previous studies of hemoglobin adducts formed in trout and environmental carp exposed to musk xylene (MX) and musk ketone (MK). Gas chromatography-electron capture negative ion chemical ionization-mass spectrometry (GC-NICI-MS) employing selected ion monitoring is used to measure 4-amino-MX (4-AMX), 2-amino-MX (2-AMX), and 2-amino-MK (2-AMK) released by alkaline hydrolysis from the sulfinamide adducts of hemoglobin. Dose-response and toxicokinetics were investigated using this sensitive method for analysis of these metabolites. In the dose-response investigation, the concentrations of 4-AMX and 2-2AMX are observed to pass through a maximum at 0.10 mg/g. In the case of 2-AMK, the adduct concentration is almost the same at dosages in the range of 0.030 to 0.10 mg/g. For toxicokinetics, the concentration of the metabolites in the Hb reaches a maximum in the 3-day sample after administration of MX or MK. Further elimination of the metabo

Superovulation induction in the house musk shrew (Suncus murinus).

PubMed

Matsuzaki, T; Matsuzaki, K; Yokoyama, M; Yamada, S; Saito, M

1997-07-01

The number of ovulated oocytes in the adult house musk shrews was examined by natural mating. The positive rate of ovulation was 83.3%, and the mean number of ovulated oocytes was 4.4 +/- 1.9 (Mean +/- SD). The induction of superovulation was examined by administering either pregnant mare's serum gonadotropin (PMSG) or human chorionic gonadotropin (hCG), exogenous gonadotropin, to house musk shrews. As a result, the number of ovulated oocytes were within the number of oocytes ovulated spontaneously. The method of superovulation induction by administering both PMSG and hCG to house musk shrews was investigated. In the group intraperitoneally with 7.5 i.u. of PMSG followed by 7.5 i.u. of hCG 48 hr later, the positive rate of ovulation was as high as 94.6% and the mean number of ovulated oocytes was 11.7 +/- 13.4. Moreover, in 15 out of these 35 animals positive for ovulation, 10 oocytes or more were observed and the mean number of ovulated oocytes was 21.0 +/- 16.5, showing the superovulatory response. In the group of 5.0 i.u. PMSG and 5.0 i.u. hCG injected at an interval of 72 hr, every animal was induced to ovulate and the mean number of ovulated oocytes was 41.3 +/- 19.9. Thus, the injection of PMSG and hCG at a longer interval increased the number of superovulated oocytes. Furthermore, 97.5% of eggs recovered from superovulating animals contained cumulus cells.

Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms.

PubMed

Phillips, William D; Vincent, Angela

2016-01-01

Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms.

Word Syntax of Nominal Compounds: Internal and Aphasiological Evidence from Turkish

ERIC Educational Resources Information Center

Tat, Deniz

2013-01-01

This dissertation is an analysis of two types of nominal compounds in Turkish, primary compounds and synthetic compounds within the framework of Distributed Morphology. A nominal primary compound is formed by two nouns, and its meaning is largely determined by world knowledge. A synthetic compound, on the other hand, is formed by a noun and a…

Analysis of Parent Synthetic Cannabinoids in Blood and Urinary Metabolites by Liquid Chromatography Tandem Mass Spectrometry.

PubMed

Knittel, Jessica L; Holler, Justin M; Chmiel, Jeffrey D; Vorce, Shawn P; Magluilo, Joseph; Levine, Barry; Ramos, Gerardo; Bosy, Thomas Z

2016-04-01

Synthetic cannabinoids emerged on the designer drug market in recent years due to their ability to produce cannabis-like effects without the risk of detection by traditional drug testing techniques such as immunoassay and gas chromatography-mass spectrometry. As government agencies work to schedule existing synthetic cannabinoids, new, unregulated and structurally diverse compounds continue to be developed and sold. Synthetic cannabinoids undergo extensive metabolic conversion. Consequently, both blood and urine specimens may play an important role in the forensic analysis of synthetic cannabinoids. It has been observed that structurally similar synthetic cannabinoids follow common metabolic pathways, which often produce metabolites with similar metabolic transformations. Presented are two validated quantitative methods for extracting and identifying 15 parent synthetic cannabinoids in blood, 17 synthetic cannabinoid metabolites in urine and the qualitative identification of 2 additional parent compounds. The linear range for most synthetic cannabinoid compounds monitored was 0.1-10 ng/mL with the limit of detection between 0.01 and 0.5 ng/mL. Selectivity, specificity, accuracy, precision, recovery and matrix effect were also examined and determined to be acceptable for each compound. The validated methods were used to analyze a compilation of synthetic cannabinoid investigative cases where both blood and urine specimens were submitted. The study suggests a strong correlation between the metabolites detected in urine and the parent compounds found in blood. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PERFLUORINATED AROMATIC COMPOUND

DTIC Science & Technology

octafluorobiphenyl, and perfluoroaliphatic aldehydes. Synthetic routes to perfluoro cyclohexyls via reactions of phenyl and pentafluorphenyl lithium with...other perfluorinated aromatic compounds were employed in the synthesis of perfluorinated aromatic model compounds and polymers. The hydrogenic analogues...hydrazides, and imides. Synthetic routes to perfluoro aralkyl compounds are being investigated. Starting materials are tetrafluorobenzene

Synthetic Chemicals with Potential for Natural Attenuation (Postprint)

DTIC Science & Technology

2012-07-01

The purpose of this paper is to describe examples of other synthetic organic compounds that are known to be biodegradable ...chlorophenols are unusual among the synthetic compounds discussed here in that they can be very toxic to microorganisms . They are often used as biocides...widely distributed. In contract, bacteria able to grow at the expense of chlorinated aliphatic compounds are less common and the

Selected trace-element and synthetic-organic compound data for streambed sediment from the Clark Fork-Pend Oreille and Spokane River basins, Montana, Idaho, and Washington, 1998

USGS Publications Warehouse

Beckwith, Michael A.

2002-01-01

Most of the analytical results for synthetic organic compounds were reported as either estimated or non-detected values. Phthalates and polycyclic aro­matic hydrocarbons were the most frequently detected classes of synthetic organic compounds in streambed sediment. Organochlorine pesticide residues were detected at two sites. Polychlorinated biphenyls were detected at one site.

Behaviour of pharmaceuticals and personal care products in a sewage treatment plant of northwest Spain.

PubMed

Carballa, M; Omil, F; Lema, J M; Llompart, M; García, C; Rodriguez, I; Gómez, M; Ternes, T

2005-01-01

Thirteen pharmaceutical and cosmetic compounds have been surveyed along the different units of a municipal sewage treatment plant (STP) to study their fate across each step and the overall removal efficiency. The STP studied corresponds to a population of approximately 100,000 inhabitants located in Galicia (northwest Spain), including three main sections: pre-treatment (coarse and fine screening, grit and fat removal); primary treatment (sedimentation tanks); and secondary treatment (conventional activated sludge). Among all the substances considered (galaxolide, tonalide, carbamazepine, diazepam, diclofenac, ibuprofen, naproxen, estrone, estradiol, ethinylestradiol, roxitromycin, sulfamethoxazole and iopromide), only significant concentrations were found for two musks (galaxolide and tonalide), two antiphlogistics (ibuprofen and naproxen), two natural estrogens (estrone, estradiol), one antibiotic (sulfamethoxazole) and the X-ray contrast media (iopromide), being the other compounds below the quantification level. In the primary treatment, only the fragrances were partly removed, with efficiencies of 20-50% for galaxolide and tonalide. However, the aerobic treatment caused an important reduction in all compounds detected, between 35 and 75%, with the exception of iopromide. The overall removal efficiency of the STP ranged between 70 and 90% for the fragrances, 45 and 70% for the acidic compounds, around 67% for estradiol and 57% for the antibiotic sulfamethoxazole.

Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms

PubMed Central

Phillips, William D.; Vincent, Angela

2016-01-01

Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms. PMID:27408701

Development of an ultrasensitive PCR assay for polycyclic musk determination in fish.

PubMed

Zhang, Xiaohan; Zhuang, Huisheng

2018-05-01

Polycyclic musks (PCMs) in the aquatic environment and organisms have become an emerging environmental issue because of their potential risk. The most used method for polycyclic musk determination is gas chromatography-mass spectrometry (GC-MS) with different sample extractions, which are somewhat expensive to operate, complex and laborious. In this study, a novel and ultrasensitive real-time polymerase chain reaction (PCR) assay with multiple signal amplification of carboxylic-DNA by gold nanoparticle-polyamidoamine conjugation (Au-PAMAM) was developed for determining polycyclic musks in fish. Hapten and immunogen were specially prepared. Polyclonal antibodies were produced based on the optimal immunisation, and the antibodies were characterised. Due to PAMAM's unique nanostructure of numerous functional amino groups, polyclonal antibody and carboxylic-DNA were immobilised by Au-PAMAM conjugation to develop the antibody-Au-PAMAM-DNA probes, which were used as a signal DNA amplifier in the PCR system. Compared with real-time immuno-PCR, this biological probe-amplified immuno-PCR (BPAI-PCR) assay had higher sensitivity due to the probes' higher ratio of signal DNA. Finally, the BPAI-PCR assay was applied to analyse AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene,Tonalide) concentrations in fish samples in the range from 1 pg/L to 10 ng/L, giving an of LOD 0.61 pg/L. In general, due to the specificity of the antibody and novel nanoprobe design, this BPAI-PCR assay provided a potential way for trace analysis of AHTN in the aquatic organisms. The high concentrations of AHTN found in cultivated fish should encourage further toxicological studies.

Transient neonatal myasthenia gravis due to a mother with ocular onset of anti-muscle specific kinase myasthenia gravis.

PubMed

Lee, Ju-Yeun; Min, Ju-Hong; Han, Sueng-Han; Han, Jinu

2017-07-01

We describe a 27-year-old pregnant female with new onset of conjugate gaze deficit during the third trimester of pregnancy. Repetitive nerve stimulation tests, neostigmine tests, and acetylcholine receptor antibody assays were all negative. The patient delivered a normal healthy baby at a local clinic via cesarean section. The baby became hypotonic and had respiratory failure several minutes after birth. The result of acetylcholine receptor antibody was negative in the neonate. The neonate became healthy spontaneously and was extubated after 21 days of ventilation care. Two months after delivery, the mother developed ptosis and generalized symptoms and subsequent workup revealed she was muscle specific kinase (MuSK) antibody positive. The neonate was presumed to have an anti-MuSK-mediated transient neonatal myasthenia gravis. Although MuSK antibody testing is rarely indicated in ocular myasthenia gravis, MuSK antibody testing is necessary in pregnant women who are presumed ocular myasthenia gravis to warn occurrence of transient neonatal myasthenia gravis. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-MuSK myasthenia gravis with prolonged remission.

PubMed

Bouwyn, Jean Paul; Magnier, Patrick; Bédat-Millet, Anne-Laure; Ahtoy, Patrick; Maltête, David; Lefaucheur, Romain

2016-07-01

Myasthenia gravis (MG) with antibodies against muscle-specific tyrosine kinase (MuSK) is a rare disorder of neuromuscular transmission affecting preferentially bulbar, neck and respiratory muscles. We report the case of a 22-year-old man who presented with diplopia on lateral gaze to both sides, facial diplegia, nasal dysarthria and dysphagia. Repetitive nerve stimulation of the trapezius and orbicularis oculi muscles showed amplitude decrements of 19% and 41% respectively supporting the diagnosis of myasthenia gravis. MUsK antibodies were positive. Corticosteroids were introduced and then tapered and discontinued at 6 months after initiation. The patient remained in remission and asymptomatic for 4 years without ongoing treatment or prior treatment with rituximab after this first relapse of MuSK-MG. MuSK- MG is considered a hard-to-treat condition and patients generally remain dependent on immunosuppression or prior treatment with rituximab. Our observation highlights that patients with MuSK-MG can have a benign course and that continued immunosuppressive or immunomodulatory therapy may not always be required. Copyright © 2016 Elsevier B.V. All rights reserved.

Hyperloops, Nuclear Spacecraft, and the New York City Subway

NASA Astrophysics Data System (ADS)

Granade, Stephen

2014-03-01

Frustrated by the speed and high cost-per-mile of the California High-Speed Rail project linking Los Angeles with San Francisco, Elon Musk proposed the Hyperloop: a high-speed train running in a sealed, partially-evacuated tube. Musk released a white paper that described the technology and concluded that the Hyperloop could be built for less than a tenth of a cost of the California High-Speed Rail. Musk's white paper focused heavily on the scientific and technical questions that must be answered, but public transportation is a domain at the intersection of science and society. Public transportation infrastructure is shaped as much by the pressures of government and citizens as by the technology behind the transportation. Tube-based transport like the Hyperloop has been proposed before, but has never gone further than words on a page. Why? Historical examples like the development of the New York City subway and the proposed nuclear-powered Orion spacecraft shed light on the societal barriers that new transportation must overcome, and help illuminate why technology-based answers are not a full response to transportation questions.

Analytical methods for the determination of personal care products in human samples: an overview.

PubMed

Jiménez-Díaz, I; Zafra-Gómez, A; Ballesteros, O; Navalón, A

2014-11-01

Personal care products (PCPs) are organic chemicals widely used in everyday human life. Nowadays, preservatives, UV-filters, antimicrobials and musk fragrances are widely used PCPs. Different studies have shown that some of these compounds can cause adverse health effects, such as genotoxicity, which could even lead to mutagenic or carcinogenic effects, or estrogenicity because of their endocrine disruption activity. Due to the absence of official monitoring protocols, there is an increasing demand of analytical methods that allow the determination of those compounds in human samples in order to obtain more information regarding their behavior and fate in the human body. The complexity of the biological matrices and the low concentration levels of these compounds make necessary the use of advanced sample treatment procedures that afford both, sample clean-up, to remove potentially interfering matrix components, as well as the concentration of analytes. In the present work, a review of the more recent analytical methods published in the scientific literature for the determination of PCPs in human fluids and tissue samples, is presented. The work focused on sample preparation and the analytical techniques employed. Copyright © 2014 Elsevier B.V. All rights reserved.

Pyridostigmine but not 3,4-diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle-specific kinase autoantibody

PubMed Central

Morsch, Marco; Reddel, Stephen W; Ghazanfari, Nazanin; Toyka, Klaus V; Phillips, William D

2013-01-01

In myasthenia gravis, the neuromuscular junction is impaired by the antibody-mediated loss of postsynaptic acetylcholine receptors (AChRs). Muscle weakness can be improved upon treatment with pyridostigmine, a cholinesterase inhibitor, or with 3,4-diaminopyridine, which increases the release of ACh quanta. The clinical efficacy of pyridostigmine is in doubt for certain forms of myasthenia. Here we formally examined the effects of these compounds in the antibody-induced mouse model of anti-muscle-specific kinase (MuSK) myasthenia gravis. Mice received 14 daily injections of IgG from patients with anti-MuSK myasthenia gravis. This caused reductions in postsynaptic AChR densities and in endplate potential amplitudes. Systemic delivery of pyridostigmine at therapeutically relevant levels from days 7 to 14 exacerbated the anti-MuSK-induced structural alterations and functional impairment at motor endplates in the diaphragm muscle. No such effect of pyridostigmine was found in mice receiving control human IgG. Mice receiving smaller amounts of MuSK autoantibodies did not display overt weakness, but 9 days of pyridostigmine treatment precipitated generalised muscle weakness. In contrast, one week of treatment with 3,4-diaminopyridine enhanced neuromuscular transmission in the diaphragm muscle. Both pyridostigmine and 3,4-diaminopyridine increase ACh in the synaptic cleft yet only pyridostigmine potentiated the anti-MuSK-induced decline in endplate ACh receptor density. These results thus suggest that ongoing pyridostigmine treatment potentiates anti-MuSK-induced AChR loss by prolonging the activity of ACh in the synaptic cleft. PMID:23440963

Pyridostigmine but not 3,4-diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle-specific kinase autoantibody.

PubMed

Morsch, Marco; Reddel, Stephen W; Ghazanfari, Nazanin; Toyka, Klaus V; Phillips, William D

2013-05-15

In myasthenia gravis, the neuromuscular junction is impaired by the antibody-mediated loss of postsynaptic acetylcholine receptors (AChRs). Muscle weakness can be improved upon treatment with pyridostigmine, a cholinesterase inhibitor, or with 3,4-diaminopyridine, which increases the release of ACh quanta. The clinical efficacy of pyridostigmine is in doubt for certain forms of myasthenia. Here we formally examined the effects of these compounds in the antibody-induced mouse model of anti-muscle-specific kinase (MuSK) myasthenia gravis. Mice received 14 daily injections of IgG from patients with anti-MuSK myasthenia gravis. This caused reductions in postsynaptic AChR densities and in endplate potential amplitudes. Systemic delivery of pyridostigmine at therapeutically relevant levels from days 7 to 14 exacerbated the anti-MuSK-induced structural alterations and functional impairment at motor endplates in the diaphragm muscle. No such effect of pyridostigmine was found in mice receiving control human IgG. Mice receiving smaller amounts of MuSK autoantibodies did not display overt weakness, but 9 days of pyridostigmine treatment precipitated generalised muscle weakness. In contrast, one week of treatment with 3,4-diaminopyridine enhanced neuromuscular transmission in the diaphragm muscle. Both pyridostigmine and 3,4-diaminopyridine increase ACh in the synaptic cleft yet only pyridostigmine potentiated the anti-MuSK-induced decline in endplate ACh receptor density. These results thus suggest that ongoing pyridostigmine treatment potentiates anti-MuSK-induced AChR loss by prolonging the activity of ACh in the synaptic cleft.

Molecular cloning and evolutionary analysis of captive forest musk deer bitter taste receptor gene T2R16.

PubMed

Zhao, G J; Wu, N; Li, D Y; Zeng, D J; Chen, Q; Lu, L; Feng, X L; Zhang, C L; Zheng, C L; Jie, H

2015-12-08

Sensing bitter tastes is crucial for most animals because it can prevent them from ingesting harmful food. This process is mainly mediated by the bitter taste receptors (T2R) that are largely expressed in the taste buds. Previous studies have identified some T2R gene repertoires. Marked variation in repertoire size has been noted among species. However, research on T2Rs is still limited and the mechanisms underlying the evolution of vertebrate T2Rs remain poorly understood. In the present study, we analyzed the structure and features of the protein encoded by the forest musk deer (Moschus berezovskii) T2R16 and submitted the gene sequence to NCBI GenBank. The results showed that the full coding DNA sequence (CDS) of musk deer T2R16 (GenBank accession No. KP677279) was 906 bp, encoding 301 amino acids, which contained ATG start codon and TGA stop codon, with a calculated molecular weight of 35.03 kDa and an isoelectric point of 9.56. The T2R16 protein receptor had seven conserved transmembrane regions. Hydrophobicity analysis showed that most amino acid residues in T2R16 protein were hydrophobic, and the grand average of hydrophobicity (GRAVY) was 0.657. Phylogenetic analysis based on this gene revealed that forest musk deer had the closest association with sheep (Ovis aries), as compared to cow (Bos taurus), Tursiops truncatus, and other species, whereas it was genetically farthest from humans (Homo sapiens). We hope these results would complement the existing data on T2R16 and encourage further research in this respect.

Thermodynamic Analysis of Ionic Compounds: Synthetic Applications.

ERIC Educational Resources Information Center

Yoder, Claude H.

1986-01-01

Shows how thermodynamic cycles can be used to understand trends in heats of formation and aqueous solubilities and, most importantly, how they may be used to choose synthetic routes to new ionic compounds. (JN)

Muscle-Specific Tyrosine Kinase and Myasthenia Gravis Owing to Other Antibodies.

PubMed

Rivner, Michael H; Pasnoor, Mamatha; Dimachkie, Mazen M; Barohn, Richard J; Mei, Lin

2018-05-01

Around 20% of patients with myasthenia gravis are acetylcholine receptor antibody negative; muscle-specific tyrosine kinase antibodies (MuSK) were identified as the cause of myasthenia gravis in 30% to 40% of these cases. Anti MuSK myasthenia gravis is associated with specific clinical phenotypes. One is a bulbar form with fewer ocular symptoms. Others show an isolated head drop or symptoms indistinguishable from acetylcholine receptor-positive myasthenia gravis. These patients usually respond well to immunosuppressive therapy, but not as well to cholinesterase inhibitors. Other antibodies associated with myasthenia gravis, including low-density lipoprotein receptor-related protein 4, are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Home range characteristics and overwintering ecology of the stripe-necked musk turtle (Sternotherus minor peltifer) in middle Tennessee

USGS Publications Warehouse

Ennen, Joshua R.; Scott, A. Floyd

2013-01-01

Little is known about the movement behavior of the stripe-necked musk turtle, Sternotherus minor peltifer. Using radiotelemetry, we calculated mean (± SD) home range length, which was 341.4 ± 90.3 m, with home range length not differing between the sexes (males, 335 ± 194 m; females, 346 ± 79.5 m). Sternotherus m. peltifer were active in every month of the year but decreased their movement distance and frequency between December and March; during nonwinter and winter periods, individuals used limestone bluffs most often.

MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK.

PubMed

Küçükerden, Melike; Huda, Ruksana; Tüzün, Erdem; Yılmaz, Abdullah; Skriapa, Lamprini; Trakas, Nikos; Strait, Richard T; Finkelman, Fred D; Kabadayı, Sevil; Zisimopoulou, Paraskevi; Tzartos, Socrates; Christadoss, Premkumar

2016-06-15

Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1+, IgG2+ and IgG3+ peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthetic Cathinone and Cannabinoid Designer Drugs Pose a Major Risk for Public Health

PubMed Central

Weinstein, Aviv M.; Rosca, Paola; Fattore, Liana; London, Edythe D.

2017-01-01

As part of an increasing worldwide use of designer drugs, recent use of compounds containing cathinones and synthetic cannabinoids is especially prevalent. Here, we reviewed current literature on the prevalence, epidemiology, bio-behavioral effects, and detection of these compounds. Gender differences and clinical effects will also be examined. Chronic use of synthetic cathinone compounds can have major effects on the central nervous system and can induce acute psychosis, hypomania, paranoid ideation, and delusions, similar to the effects of other better-known amphetamine-type stimulants. Synthetic cannabinoid products have effects that are somewhat similar to those of natural cannabis but more potent and long-lasting than THC. Some of these compounds are potent and dangerous, having been linked to psychosis, mania, and suicidal ideation. Novel compounds are developed rapidly and new screening techniques are needed to detect them as well as a rigorous regulation and legislation reinforcement to prevent their distribution and use. Given the rapid increase in the use of synthetic cathinones and cannabinoid designer drugs, their potential for dependence and abuse, and harmful medical and psychiatric effects, there is a need for research and education in the areas of prevention and treatment. PMID:28878698

Environmental risk assessment of polycyclic musks HHCB and AHTN in consumer product chemicals in China.

PubMed

Fan, Ming; Liu, Zhengtao; Dyer, Scott; Xia, Pu; Zhang, Xiaowei

2017-12-01

An environmental risk assessment (ERA) framework was recently developed for consumer product chemicals in China using a tiered approach, applying an existing Chinese regulatory qualitative method in Tier Zero and, then, utilizing deterministic and probabilistic methods for Tiers One and Two. The exposure assessment methodology in the framework applied conditions specific to China including physical setting, infrastructure, and consumers' habits and practices. Furthermore, two scenarios were identified for quantitatively assessing environmental exposure: (1) Urban with wastewater treatment, and; (2) Rural without wastewater treatment (i.e., direct-discharge of wastewater). Upon a brief discussion on the framework methodology, this paper primarily presented a case study conducted using this new approach for assessing two fragrance chemicals, the polycyclic musks HHCB (Galaxolide, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-[gamma]-2-benzopyran) and AHTN (Tonalide, 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene). Both HHCB and AHTN are widely used as fragrances in a variety of consumer products in China, and occurrences of both compounds have been reported in wastewater influents, effluents, and sludge, in addition to surface water and sediments across several major metropolitan regions throughout China. This case study illustrated the very conservative nature of Tier Zero, which indicated a high risk potential of the fragrances to receiving water aquatic communities due to the fragrance's non-ready biodegradability and eco-toxicity profiles. However, the higher-tiered assessments (including deterministic and site-specific probabilistic) demonstrated greater environmental realism with the conclusion of HHCB and AHTN posing minimal risk, consistent with local monitoring data as well as a recent similar study conducted in the United States. Copyright © 2017 Elsevier B.V. All rights reserved.

A Multi-tracer Approach to Determining the Fate of Wastewater in Groundwater

NASA Astrophysics Data System (ADS)

Moran, J. E.; Beller, H. R.; Leif, R.; Singleton, M. J.

2006-12-01

In California, demand for limited fresh water supplies for use as drinking water has increased, and recycled water is increasingly used for irrigation or for groundwater recharge. In this study, analysis of multiple tracers, including general minerals, stable isotopes of the water molecule (for source water identification and evidence for evaporation) and of nitrate (wastewater denitrification indicators), and tritium-helium groundwater age, allow identification and quantification of the fraction of water produced at a well that originated as applied wastewater effluent. Wastewater target compounds include metabolites of alkylphenol ethoxylate nonionic surfactants, pharmaceuticals such as ibuprofen and carbamazepine, personal care products such as triclosan and polycyclic musk fragrance compounds, the insect repellent DEET, and caffeine. In spite of a high fraction (up to 70 percent) of wastewater recharge produced at monitoring wells from two sites (in Livermore, CA and Gilroy, CA), the only detections greater than 50 ng/L were of alkylphenol carboxylic acids and the anti-seizure pharmaceuticals carbamazepine and primadone. However, even these compounds occurred at concentrations in groundwater that were significantly lower than concentrations observed in treated wastewater effluent. This work was performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under contract No. W-7405-ENG-48.

SpaceX Dragon Cargo Transfer

NASA Image and Video Library

2012-06-13

NASA Administrator Charles Bolden, left, and SpaceX CEO and Chief Designer Elon Musk, view the historic Dragon capsule, right, that returned to Earth on May 31 following the first successful mission by a private company to carry supplies to the International Space Station on Wednesday, June 13, 2012 at the SpaceX facility in McGregor, Texas. Bolden and Musk also thanked the more than 150 SpaceX employees working at the McGregor facility for their role in the historic mission. Some of the 1,367 pounds of cargo the SpaceX Dragon spacecraft returned to Earth from the space station are seen in a clean room to the left. Photo Credit: (NASA/Bill Ingalls)

Qualitative Analysis and Detection of the Pyrolytic Products of JWH-018 and 11 Additional Synthetic Cannabinoids in the Presence of Common Herbal Smoking Substrates.

PubMed

Raso, Stephen; Bell, Suzanne

2017-07-01

Synthetic cannabinoids have become a ubiquitous challenge in forensic toxicology and seized drug analysis. Thermal degradation products have yet to be identified and evaluated for toxicity in comparison to parent and metabolic compounds. An investigation into these pyrolytic products, as the major route of ingestion is inhalation, may produce additional insight to understand the toxicity of synthetic cannabinoids. The pyrolysis of JWH-018 and 11 additional synthetic cannabinoids and six herbal plant substrates were conducted using an in-house constructed smoking simulator. After pyrolysis of herbal material alone, the plant substrate was spiked with the drug compounds to 2-5% w/w concentrations. Samples were collected, filtered, evaporated under nitrogen gas, reconstituted in methanol, and analyzed via gas chromatograph-mass spectrometer. Pyrolysis of the plant material alone produced 10 consistently observed compounds between the six plant species. The pyrolysis of the synthetic cannabinoids produced a total of 52 pyrolytic compounds, where 32 were unique to a particular parent compound and the remaining 20 were common products between multiple cannabinoids. The thermal degradation followed three major pathways that are outlined to assist in producing a predictive model for new synthetic cannabinoids that may arise in case samples. The observed pyrolytic products are also viable options for analysis in post mortem samples and the evaluation of toxicity. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dissipation of fragrance materials in sludge-amended soils.

PubMed

DiFrancesco, Angela M; Chiu, Pei C; Standley, Laurel J; Allen, Herbert E; Salvito, Daniel T

2004-01-01

A possible removal mechanism for fragrance materials (FMs) in wastewater is adsorption to sludge, and sludge application to land may be a route through which FMs are released to the soil environment. However, little is known about the concentrations and fate of FMs in soil receiving sludge application. This study was conducted to better understand the dissipation of FMs in sludge-amended soils. We first determined the spiking and extraction efficiencies for 22 FMs in soil and leachate samples. Nine FMs were detected in digested sludges from two wastewater treatment plants in Delaware using these methods. We conducted a 1-year die-away experiment which involved four different soils amended with sludge, with and without spiking of the 22 FMs. The initial dissipation of FMs in all spiked trays was rapid, and only seven FMs remained at concentrations above the quantification limits after 3 months: AHTN, HHCB, musk ketone, musk xylene, acetyl cedrene, OTNE, and DPMI. After 1 year, the only FMs remaining in all spiked trays were musk ketone and AHTN. DPMI was the only FM that leached significantly from the spiked trays, and no FMs were detected in leachate from any unspiked tray. While soil organic matter content affected the dissipation rate in general, different mechanisms (volatilization, transformation, leaching) appeared to be important for different FMs.

Splicing regulation and dysregulation of cholinergic genes expressed at the neuromuscular junction.

PubMed

Ohno, Kinji; Rahman, Mohammad Alinoor; Nazim, Mohammad; Nasrin, Farhana; Lin, Yingni; Takeda, Jun-Ichi; Masuda, Akio

2017-08-01

We humans have evolved by acquiring diversity of alternative RNA metabolisms including alternative means of splicing and transcribing non-coding genes, and not by acquiring new coding genes. Tissue-specific and developmental stage-specific alternative RNA splicing is achieved by tightly regulated spatiotemporal regulation of expressions and activations of RNA-binding proteins that recognize their cognate splicing cis-elements on nascent RNA transcripts. Genes expressed at the neuromuscular junction are also alternatively spliced. In addition, germline mutations provoke aberrant splicing by compromising binding of RNA-binding proteins, and cause congenital myasthenic syndromes (CMS). We present physiological splicing mechanisms of genes for agrin (AGRN), acetylcholinesterase (ACHE), MuSK (MUSK), acetylcholine receptor (AChR) α1 subunit (CHRNA1), and collagen Q (COLQ) in human, and their aberration in diseases. Splicing isoforms of AChE T , AChE H , and AChE R are generated by hnRNP H/F. Skipping of MUSK exon 10 makes a Wnt-insensitive MuSK isoform, which is unique to human. Skipping of exon 10 is achieved by coordinated binding of hnRNP C, YB-1, and hnRNP L to exon 10. Exon P3A of CHRNA1 is alternatively included to generate a non-functional AChR α1 subunit in human. Molecular dissection of splicing mutations in patients with CMS reveals that exon P3A is alternatively skipped by hnRNP H, polypyrimidine tract-binding protein 1, and hnRNP L. Similarly, analysis of an exonic mutation in COLQ exon 16 in a CMS patient discloses that constitutive splicing of exon 16 requires binding of serine arginine-rich splicing factor 1. Intronic and exonic splicing mutations in CMS enable us to dissect molecular mechanisms underlying alternative and constitutive splicing of genes expressed at the neuromuscular junction. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

At the biological modeling and simulation frontier.

PubMed

Hunt, C Anthony; Ropella, Glen E P; Lam, Tai Ning; Tang, Jonathan; Kim, Sean H J; Engelberg, Jesse A; Sheikh-Bahaei, Shahab

2009-11-01

We provide a rationale for and describe examples of synthetic modeling and simulation (M&S) of biological systems. We explain how synthetic methods are distinct from familiar inductive methods. Synthetic M&S is a means to better understand the mechanisms that generate normal and disease-related phenomena observed in research, and how compounds of interest interact with them to alter phenomena. An objective is to build better, working hypotheses of plausible mechanisms. A synthetic model is an extant hypothesis: execution produces an observable mechanism and phenomena. Mobile objects representing compounds carry information enabling components to distinguish between them and react accordingly when different compounds are studied simultaneously. We argue that the familiar inductive approaches contribute to the general inefficiencies being experienced by pharmaceutical R&D, and that use of synthetic approaches accelerates and improves R&D decision-making and thus the drug development process. A reason is that synthetic models encourage and facilitate abductive scientific reasoning, a primary means of knowledge creation and creative cognition. When synthetic models are executed, we observe different aspects of knowledge in action from different perspectives. These models can be tuned to reflect differences in experimental conditions and individuals, making translational research more concrete while moving us closer to personalized medicine.

Railroad Regulation: Changes in Freight Railroad Rates from 1997 through 2000

DTIC Science & Technology

2002-06-01

Routes, 1990–2000 19 Figure 5: Real Rail Rates for Plastic Materials or Synthetic Fibers, Resins, or Rubbers, Selected Short-Distance Routes, 1990–2000...Compounds, Selected Short-, Medium-, and Long-Distance Routes, 1990–2000 39 Figure 14: Real Rail Rates for Plastic Materials or Synthetic Fibers, Resins...Transportation Board to determine rates for coal, grain (wheat and corn), chemicals (potassium and sodium compounds and plastic materials or synthetic

Pharmaceuticals and personal care products (PPCPs): a review on environmental contamination in China.

PubMed

Liu, Jin-Lin; Wong, Ming-Hung

2013-09-01

Pharmaceuticals and personal care products (PPCPs) which contain diverse organic groups, such as antibiotics, hormones, antimicrobial agents, synthetic musks, etc., have raised significant concerns in recently years for their persistent input and potential threat to ecological environment and human health. China is a large country with high production and consumption of PPCPs for its economic development and population growth in recent years. This may result in PPCP contamination in different environmental media of China. This review summarizes the current contamination status of different environment media, including sewage, surface water, sludge, sediments, soil, and wild animals, in China by PPCPs. The human body burden and adverse effects derived from PPCPs are also evaluated. Based on this review, it has been concluded that more contamination information of aquatic environment and wildlife as well as human body burden of PPCPs in different areas of China is urgent. Studies about their environmental behavior and control technologies need to be conducted, and acute and chronic toxicities of different PPCP groups should be investigated for assessing their potential ecological and health risks. © 2013.

Estimation of Flattened Musk Turtle (Sternotherus depressus) survival, recapture, and recovery rate during and after a disease outbreak

USGS Publications Warehouse

Fonnesbeck, C.J.; Dodd, C.K.

2003-01-01

We estimated survivorship, recapture probabilities and recovery rates in a threatened population of Flattened Musk Turtles (Sternotherus depressus) through a disease outbreak in Alabama in 1985. We evaluated a set of models for the demographic effects of disease by analyzing recaptures and recoveries simultaneously. Multiple-model inference suggested survival was temporally dynamic, whereas recapture probability was sex- and age-specifc. Biweekly survivorship declined from 98-99% before to 82-88% during the outbreak. Live recapture was twice as likely for male turtles relative to juveniles or females, whereas dead recoveries varied only slightly by sex and age. Our results suggest modest reduction in survival over a relatively short time period may severely affect population status.

Incidence of dental lesions in musk shrews (Suncus murinus) and their association with sex, age, body weight and diet.

PubMed

Dudley, Emily S; Grunden, Beverly K; Crocker, Conan; Boivin, Gregory P

2013-10-22

Both wild and laboratory strains of the musk shrew (Suncus murinus) have a high incidence of periodontitis. The authors completed necropsy examinations in 51 shrews to identify dental lesions including tooth loss, mobility and fractures. Dental lesions were identified in significantly more females than males, and older animals were more likely to have lesions present. Shrews with one or more dental lesions weighed significantly less than those without lesions present. Dietary supplementation with mealworms did not significantly affect the incidence of dental lesions or the body weight of male or female shrews. The authors recommend routine body weight measurement as a simple, noninvasive method of detecting shrews with an increased likelihood of having dental lesions.

Anesthetic Management of a Patient With Antimuscle-Specific Kinase Antibody-Positive Myasthenia Gravis Undergoing an Open Cholecystectomy: A Case Report.

PubMed

Akatsu, Masahiko; Ikegami, Yukihiro; Tase, Choichiro; Nishikawa, Koichi

2017-03-15

Myasthenia gravis (MG) is an autoimmune disease characterized by the production of antibodies against the acetylcholine receptor, muscle-specific kinase (MuSK), or other proteins at the neuromuscular junction. MG with antibodies against MuSK (MuSK-MG) has been described recently. Here, we report the first case of anesthetic management of a patient with MuSK-MG undergoing an open cholecystectomy. In our case, propofol and remifentanil-based anesthesia were used for successful management without using muscle relaxants. Patients with MuSK-MG have predominantly ocular, bulbar, and respiratory symptoms that may increase the risk of aspiration. Anesthesiologists need to pay attention to perioperative respiratory failure and respiratory crisis.

Synthetic approaches to aromatic belts: building up strain in macrocyclic polyarenes.

PubMed

Eisenberg, David; Shenhar, Roy; Rabinovitz, Mordecai

2010-08-01

This tutorial review discusses synthetic strategies towards aromatic belts, defined here as double-stranded conjugated macrocycles, such as [n]cyclacenes, [n]cyclophenacenes, Schlüter belt, and Vögtle belt. Their appeal stems, firstly, from the unique nature of their conjugation, having p orbitals oriented radially rather than perpendicular to the plane of the macrocycle. Secondly, as aromatic belts are model compounds of carbon nanotubes of different chiralities, a synthetic strategy towards the buildup of structural strain in these compounds could finally open a route towards rational chemical synthesis of carbon nanotubes. The elusiveness of these compounds has stimulated fascinating and ingenious synthetic strategies over the last decades. The various strategies are classified here by their approach to the buildup of structural strain, which is the main obstacle in the preparation of these curved polyarenes.

Passive sampling - a tool for targeted screening of emerging pollutants in rivers

NASA Astrophysics Data System (ADS)

Kodes, Vit; Grabic, Roman

2016-04-01

A screening of more than 300 pollutants such as pharmaceuticals (analgesics, psycholeptics, antidepressants, antibiotics, beta blockers), PCPs (UV blockers, musk's, repellents), illicit drugs, pesticides, perfluorinated compounds and their metabolites at 22 monitoring sites throughout the Czech Republic was conducted in 2013. POCIS samplers were used in this study. Two types of passive samplers (pesticide and pharmaceutical POCIS) were deployed for 14 days in May and in October, 88 samples were collected in total. In total 265 and 310 target compounds were analyzed in pharmaceutical and pesticide samplers respectively. The chemicals of interest were extracted from the passive samplers according to standardized procedures. LC -MS/MS and LC-MS/HRMS methods were applied for analyses of extracts. 150 of 310 (48%) and 127 of 265 (48%) analyzed substances had been found in pesticide and pharmaceutical samplers respectively. 27 substances (pharmaceuticals, PCPs, pesticides, caffeine, nicotine metabolite cotinine) occurred at all sampled sites, additional 39 substances (pharmaceuticals, PCPs, pesticides) occurred at more than 17 (75%) sites. One of perfluorinated compounds (PFOA) occurred at 68% of sites, whilst one of illicit drugs (Methamphetamine) was found at 61% of sites. The highest number of contaminants found in one POCIS at a single monitoring site was 111. The concentrations varied from nanograms to thousands of nanograms per sampler. Emerging contaminants occurring in highest concentrations (> 1000 ng/sampler) were BP-4 and PBSA (UV blockers), caffeine, DEET (insect repellent), imidacloprid (insecticide), telmisartan (hypertension drug) and tramadol (analgesic). Monitoring in the Czech Republic has demonstrated that many target compounds enter river waters and a number of these compounds reach high concentrations.

Personal care compounds in a reed bed sludge treatment system.

PubMed

Chen, Xijuan; Pauly, Udo; Rehfus, Stefan; Bester, Kai

2009-08-01

Sewage sludge (also referred to as biosolids) has long been used as fertilizer on agricultural land. The usage of sludge as fertilizer is controversial because of possible high concentration of xenobiotic compounds, heavy metals as well as pathogens. In this study, the fate of the xenobiotic compounds triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol), OTNE (1-(2,3,8,8-tetramethyl-1,2,3,4,5,6,7,8-octahydro-naphthalen-2-yl)ethan-1-one), HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-benzopyran), HHCB-lactone, AHTN (7-acetyl-1,1,3,4,4,6 hexamethyl-1,2,3,4 tetrahydronaphthalene), and DEHP (bis(2-ethylhexyl)phthalate) in advanced biological treatment of sludge was determined. During 13months of field-incubation of the sludge in reed beds, the xenobiotic compounds were analysed. The bactericide triclosan was reduced to 60%, 45%, and 32% of its original concentration in the top, middle, and bottom layer. The fragrance OTNE was decreased to 42% in the top layer, 53% in the middle layer, and 70% in the bottom layer, respectively. For DEHP a reduction of 70%, 71%, and 40% was observed in the top, middle, and bottom layer, respectively. The polycyclic musk compounds HHCB, AHTN, and the primary metabolite of HHCB, i.e., HHCB-lactone showed no degradation in 13months during the experimental period in this installation. Tentative half-lives of degradation of triclosan, OTNE and DEHP were estimated to be 315-770d, 237-630d, and 289-578d, respectively.

Emerging Water Contaminants: Technical, Legal and Policy Challenges

NASA Astrophysics Data System (ADS)

Deeb, R. A.; Kresic, N.; Laugier, M. C.; Kavanaugh, M. C.

2002-12-01

Approximately 120 new chemicals are created each year due to ever-improving industry and technology markets. Releases of new contaminants into the environment can occur during production, use and disposal of these chemicals thereby leading to potential contamination of water supply sources. Very few emerging contaminants are regulated. In addition, knowledge gaps regarding emerging contaminants include lack health effects, occurrence (either because these compounds are not measured or because concentrations are below detection limits of readily available analytical techniques) and fate and transport in the environment especially with regards to mobility and persistence. The sources of these compounds are numerous. One source is treated wastewater, which is re-injected into groundwater aquifers for indirect potable reuse purposes. Emerging compounds of concern can be classified in various classes. This presentation will focus on contaminants, which have emerged in the last 10 years including pharmaceuticals (antibiotics/drugs), personal care products (polycyclic musks), pesticides/herbicides, industrial solvents (1,4-dioxane), gasoline additives (MTBE), disinfection byproducts such as NDMA (N-nitrosodimethylamine), and inorganic compounds such as perchlorate and arsenic. This presentation will present technical, legal and legislative challenges posed by the presence of these contaminants in water. Background information including chemical's history of use, sources in the environments, nationwide occurrence, physical and chemical properties, behavior in the environment and technologies for removal from soil and water will be presented. In addition, case studies on MTBE, pharmaceuticals and personal care products, 1,4-dioxane, arsenic and NDMA will be discussed.

How useful are the "other" semipermeable membrane devices (SPMDs); the mini-unit (15.2 cm long)?

USGS Publications Warehouse

Goodbred, Steven L.; Bryant, Wade L.; Rosen, Michael R.; Alvarez, David; Spencer, Terri

2009-01-01

Mini (15.2 cm) semipermeable membrane devices (SPMDs) were used successfully in 169 streams from six metropolitan areas of the US to sequester hydrophobic organic compounds (HOCs) that are indicative of urbanization. A microscale assay the P450RGS, which responds to compounds that bind to the aryl hydrocarbon receptor (AhR), and the Fluoroscan, a chemical screen for polycyclic aromatic hydrocarbons (PAHs), were performed on each mini SPMD extract. Results show both tests were sensitive enough to respond in streams with low urbanization and responded exponentially in a predictable way to a gradient of urbanization. Mini SPMDs had sufficient sampling rates to detect HOCs using gas chromatography with mass spectrometric detection (GC/MS) in streams with low levels of urbanization. The total number of HOCs in streams had a linear response to a gradient of urbanization, where 73 of 140 targeted compounds were detected. A diverse group of compounds was found in urban streams including, PAHs, insecticides, herbicides, musk fragrances, waste water treatment compounds and flame retardants. Pentachloroanisole (PCA), a breakdown product of pentachlorophenol (wood preservative), was the most ubiquitous HOC, and was detected in 71% of streams. An evaluation of mini SPMD performance showed they can detect concentrations in water below toxicity benchmarks for many HOCs with the exception of 2,3,7,8 tetrachlorodibenzo-p-dioxin. A comparison of mini SPMDs with full sized (91.4 cm) SPMDs showed they have several distinct advantages. The most notable advantages are their low cost, small size, and reduced chance of vandalism. The greatest limitation is the inability to detect compounds at low concentrations (pg/L). Mini SPMDs perform quite well in a wide array of environmental settings and applications and should be considered as an option in environmental studies.

Synthetic Aspects and Electro-Optical Properties of Fluorinated Arylenevinylenes for Luminescence and Photovoltaics

PubMed Central

Martinelli, Carmela; Farinola, Gianluca M.; Pinto, Vita; Cardone, Antonio

2013-01-01

In this review, the main synthetic aspects and properties of fluorinated arylenevinylene compounds, both oligomers and polymers, are summarized and analyzed. Starting from vinyl organotin derivatives and aryl halides, the Stille cross-coupling reaction has been successfully applied as a versatile synthetic protocol to prepare a wide series of π-conjugated compounds, selectively fluorinated on the aromatic and/or vinylene units. The impact of fluoro-functionalization on properties, the solid state organization and intermolecular interactions of the synthesized compounds are discussed, also in comparison with the non-fluorinated counterparts. Luminescent and photovoltaic applications are also discussed, highlighting the role of fluorine on the performance of devices. PMID:28809206

Formation of nitro musk adducts of rainbow trout hemoglobin for potential use as biomarkers of exposure.

PubMed

Mottaleb, M A; Zhao, X; Curtis, L R; Sovocool, G W

2004-05-12

The high use of nitro musk xylene (MX) and musk ketone (MK) as fragrances, and their persistence and bioaccumulation potential make them ubiquitous environmental contaminants. The 4-amino-MX (AMX) and 2-amino-MK (AMK) metabolites have been detected in trout fish hemoglobin (Hb) samples by gas chromatography-ion trap-mass spectrometry (GC-MS). Twelve Hb samples prepared from rainbow trout that were exposed to MX and MK, over a period of 24 and 72 h, were analyzed. Amino metabolites were liberated by basic hydrolysis and extracted from the fish Hb into n-hexane. The extract was concentrated, analyzed, and spiked with a standard solution (80 pg/microl) of AMX or AMK and reanalyzed. Concentrations of AMX from 10 to 25 ng/g were detected in Hb from fish taken 24 and 72 h after MX exposure. At 24 and 72 h after MK exposure, the concentration of AMK was found to be 25-51 ng/g and 9.5-25 ng/g, respectively. Concentrations of AMK in Hb from two of the three trout were substantially lower after 72 h compared with 24 h exposure. The AMX and AMK metabolites were not detected in four control samples. Average recoveries exceeding 89 and 86% could be achieved for AMX and AMK, respectively, with a coefficient of variation (CV) around 5%.

Photo-induced oxidative damage to dissolved free amino acids by the photosensitizer polycyclic musk tonalide: Transformation kinetics and mechanisms.

PubMed

Fang, Hansun; Gao, Yanpeng; Wang, Honghong; Yin, Hongliang; Li, Guiying; An, Taicheng

2017-05-15

Residue from the polycyclic musks (PCMs) in household and personal care products may harm human beings through skin exposure. To understand the health effects of PCMs when exposed to sunlight at molecular level, both experimental and computational methods were employed to investigate the photosensitized oxidation performance of 19 natural amino acids, the most basic unit of life. Results showed that a typical PCM, tonalide, acts as a photosensitizer to significantly increase photo-induced oxidative damage to amino acids. Both common and exceptional transformation pathways occurred during the photosensitization damage of amino acids. Experimental tests further identified the different mechanisms involved. The common transformation pathway occurred through the electron transfer from α amino-group of amino acids, accompanying with the formation of O 2 •- . This pathway was controlled by the electronic density of N atom in α amino-group. The exceptional transformation pathway was identified only for five amino acids, mainly due to the reactions with reactive oxygen species, e.g. 1 O 2 and excited triplet state molecules. Additionally, tonalide photo-induced transformation products could further accelerate the photosensitization of all amino acids with the common pathway. This study may support the protection of human health, and suggests the possible need to further restrict polycyclic musks use. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthetic Aziridines in Medicinal Chemistry: A Mini-Review.

PubMed

Singh, Girija S

2016-01-01

Azaheterocyclic compounds are well-known to have diverse types of biological activity. Among them, azacyclopropanes, commonly referred as aziridines, occupy a prominent place in synthetic organic and medicinal chemistry due to its occurrence in natural resources, complexity involved in synthesis due to ring-strain, building blocks in organic synthesis, and its biological properties. Several novel compounds containing aziridine ring have been designed and synthesized recently by medicinal chemists for evaluating their biological profile. A number of compounds are reported as cysteine protease inhibitors, antibacterial, antifungal, anticancer, antileishmanial, and antimalarial agents. This review article summarizes the biological activity of such compounds. The preparation of such compounds is also described.

Human dermal exposure to galaxolide from personal care products.

PubMed

Correia, P; Cruz, A; Santos, L; Alves, A

2013-06-01

Musks are synthetic fragrances applied on personal care and household products as fixatives, by retarding the release of other fragrances with higher volatility. Galaxolide is the most used polycyclic musk since the 90th decade, and it has been detected in several environmental and biological matrices, particularly in human tissues and fluids. For exposure assessment purposes, large-monitoring data need to be obtained and rapid but reliable analytical techniques are requested. The main objective of this study is to develop and validate a new and fast analytical methodology to quantify galaxolide in personal care products and to apply this method to real matrices like skin care products (creams and lotions), shower products (soap bar), hair care products (shampoo and hair conditioner) and oral care products (toothpaste), to evaluate the human dermal exposure risk. A dispersive solid-phase extraction is proposed, using QuEChERS methodology, followed by HPLC with fluorescence detection. Some extraction parameters were studied, like the ratio of sample/solvent amounts, the homogenization time, the salt addition effect and the used sorbents. The validation parameters of the developed method were the following: a linearity range of 0.005-1.002 mg kg⁻¹ sample, a limit of detection of 0.001 mg kg⁻¹ sample, repeatability between 0.7% and 11.3% (variation coefficient of six standard injections), an intermediate precision of 2.5% (variation coefficient of six independent analysis of the same sample), mean recoveries ranging from 65% (soap bar) to 95% (body cream) and 3% of global uncertainty in most of the working range. The time of analysis, including the extraction steps, is 60 min, allowing a throughput of 4 samples h⁻¹ . Galaxolide was detected in all of the seven analysed products in concentrations ranging from 0.04 ± 0.01 mg kg⁻¹ sample (toothpaste) to 280.78 ± 8.19 mg kg⁻¹ sample (perfumed body cream), which may correspond to a significant estimated daily human dermal exposure of 904 μg day⁻¹. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Thermolytic Degradation of Synthetic Cannabinoids: Chemical Exposures and Pharmacological Consequences.

PubMed

Thomas, Brian F; Lefever, Timothy W; Cortes, Ricardo A; Grabenauer, Megan; Kovach, Alexander L; Cox, Anderson O; Patel, Purvi R; Pollard, Gerald T; Marusich, Julie A; Kevin, Richard C; Gamage, Thomas F; Wiley, Jenny L

2017-04-01

Synthetic cannabinoids are manufactured clandestinely with little quality control and are distributed as herbal "spice" for smoking or as bulk compound for mixing with a solvent and inhalation via electronic vaporizers. Intoxication with synthetic cannabinoids has been associated with seizure, excited delirium, coma, kidney damage, and other disorders. The chemical alterations produced by heating these structurally novel compounds for consumption are largely unknown. Here, we show that heating synthetic cannabinoids containing tetramethylcyclopropyl-ring substituents produced thermal degradants with pharmacological activity that varied considerably from their parent compounds. Moreover, these degradants were formed under conditions simulating smoking. Some products of combustion retained high affinity at the cannabinoid 1 (CB 1 ) and CB 2 receptors, were more efficacious than (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol (CP55,940) in stimulating CB 1 receptor-mediated guanosine 5'-O-(3-thiotriphosphate) (GTPγS) binding, and were potent in producing Δ 9 -tetrahydrocannabinol-like effects in laboratory animals, whereas other compounds had low affinity and efficacy and were devoid of cannabimimetic activity. Degradants that retained affinity and efficacy also substituted in drug discrimination tests for the prototypical synthetic cannabinoid 1-pentyl-3-(1-naphthoyl)indole (JWH-018), and are likely to produce psychotropic effects in humans. Hence, it is important to take into consideration the actual chemical exposures that occur during use of synthetic cannabinoid formulations to better comprehend the relationships between dose and effect. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Combination Chemistry: Structure-Activity Relationships of Novel Psychoactive Cannabinoids.

PubMed

Wiley, Jenny L; Marusich, Julie A; Thomas, Brian F

2017-01-01

Originally developed as research tools for use in structure-activity relationship studies, synthetic cannabinoids contributed to significant scientific advances in the cannabinoid field. Unfortunately, a subset of these compounds was diverted for recreational use beginning in the early 2000s. As these compounds were banned, they were replaced with additional synthetic cannabinoids with increasingly diverse chemical structures. This chapter focuses on integration of recent results with those covered in previous reviews. Whereas most of the early compounds were derived from the prototypic naphthoylindole JWH-018, currently popular synthetic cannabinoids include tetramethylcyclopropyl ketones and indazole-derived cannabinoids (e.g., AB-PINACA, AB-CHMINACA). Despite their structural differences, psychoactive synthetic cannabinoids bind with high affinity to CB 1 receptors in the brain and, when tested, have been shown to activate these receptors and to produce a characteristic profile of effects, including suppression of locomotor activity, antinociception, hypothermia, and catalepsy, as well as Δ 9 -tetrahydrocannabinol (THC)-like discriminative stimulus effects in mice. When they have been tested, synthetic cannabinoids are often found to be more efficacious at activation of the CB 1 receptor and more potent in vivo. Further, their chemical alteration by thermolysis during use and their uncertain stability and purity may result in exposure to degradants that differ from the parent compound contained in the original product. Consequently, while their intoxicant effects may be similar to those of THC, use of synthetic cannabinoids may be accompanied by unpredicted, and sometimes harmful, effects.

Simultaneous determination of 24 personal care products in fish muscle and liver tissues using QuEChERS extraction coupled with ultra pressure liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometer analyses.

PubMed

Yao, Li; Zhao, Jian-Liang; Liu, You-Sheng; Yang, Yuan-Yuan; Liu, Wang-Rong; Ying, Guang-Guo

2016-11-01

A sensitive and selective quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction combined with dispersive solid-phase extraction (d-SPE) cleanup method was developed to simultaneously extract a wide range of personal care products (16 biocides, 4 synthetic musks, and 4 benzotriazoles) in fish muscle and liver tissues. In order to get satisfactory recoveries, different extraction parameters were optimized, including extraction salts and d-SPE materials, extraction solvents and acetic acid contents in organic phase, and the ratios of solvent and water. Ultra pressure liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry were used to analyze the target compounds in the extracts. Among the 24 personal care products, the recoveries in the range of 70-120 % were obtained for 20, 19, and 12 analytes in fish muscle at the spiking concentrations of 10, 5, and 1 ng/g ww, respectively, and for 13, 12, and 11 analytes in liver at the spiking concentrations of 40, 20, and 4 ng/g ww, respectively. Method quantification limits (MQLs) of all analytes were 0.02-2.12 ng/g ww for fish muscle and 0.22-12.2 ng/g ww for fish liver tissues. The method was successfully applied to wild fish samples collected from Dongjiang River, south China. Twenty-one and 17 of the analytes were found in fish muscle and liver samples, respectively, in at least one site of the river with the concentrations between below MQLs and 119 ng/g ww, respectively. Graphical abstract Achieved satisfactory recoveries, high precision, and low method quantification limits (MQLs) for PCPs in wild fish tissues by QuEChERS procedure optimization combined with UPLC-MS/MS and GC-MS analyses.

Synthetic cannabinoids 2015: An update for pediatricians in clinical practice

PubMed Central

Castellanos, Daniel; Gralnik, Leonard M

2016-01-01

Synthetic cannabinoids are a group of substances in the world of designer drugs that have become increasingly popular over the past few years. Synthetic cannabinoids are a chemically diverse group of compounds functionally similar to THC. Since first appearing on the world market a few years ago these compounds have evolved rapidly. Newer more potent analogues have been developed. Identifying youth who abuse these substances can be difficult. Newer forms of consumption have also evolved. These products are now manufactured in products that look like natural cannabis resin and in liquid cartridges used in electronic cigarettes. Synthetic cannabinoids appear to be associated with potentially dangerous health effects that are more severe than that of marijuana. Some synthetic cannabinoid compounds have been associated with serious physical consequences, such as, seizures, myocardial infarction and renal damage. In addition, psychoactive effects, such as aggression, confusion, anxiety and psychosis have also been reported. The diagnosis remains primarily clinical with toxicological confirmation difficult due to manufacturers constantly developing new analogues to avoid detection. Pediatricians are urged to familiarize themselves with these drugs and the typical presentations of patients who use them. PMID:26862498

SCScore: Synthetic Complexity Learned from a Reaction Corpus.

PubMed

Coley, Connor W; Rogers, Luke; Green, William H; Jensen, Klavs F

2018-02-26

Several definitions of molecular complexity exist to facilitate prioritization of lead compounds, to identify diversity-inducing and complexifying reactions, and to guide retrosynthetic searches. In this work, we focus on synthetic complexity and reformalize its definition to correlate with the expected number of reaction steps required to produce a target molecule, with implicit knowledge about what compounds are reasonable starting materials. We train a neural network model on 12 million reactions from the Reaxys database to impose a pairwise inequality constraint enforcing the premise of this definition: that on average, the products of published chemical reactions should be more synthetically complex than their corresponding reactants. The learned metric (SCScore) exhibits highly desirable nonlinear behavior, particularly in recognizing increases in synthetic complexity throughout a number of linear synthetic routes.

Potential Inhibitors for Isocitrate Lyase of Mycobacterium tuberculosis and Non-M. tuberculosis: A Summary

PubMed Central

Lee, Yie-Vern; Wahab, Habibah A.

2015-01-01

Isocitrate lyase (ICL) is the first enzyme involved in glyoxylate cycle. Many plants and microorganisms are relying on glyoxylate cycle enzymes to survive upon downregulation of tricarboxylic acid cycle (TCA cycle), especially Mycobacterium tuberculosis (MTB). In fact, ICL is a potential drug target for MTB in dormancy. With the urge for new antitubercular drug to overcome tuberculosis treat such as multidrug resistant strain and HIV-coinfection, the pace of drug discovery has to be increased. There are many approaches to discovering potential inhibitor for MTB ICL and we hereby review the updated list of them. The potential inhibitors can be either a natural compound or synthetic compound. Moreover, these compounds are not necessary to be discovered only from MTB ICL, as it can also be discovered by a non-MTB ICL. Our review is categorized into four sections, namely, (a) MTB ICL with natural compounds; (b) MTB ICL with synthetic compounds; (c) non-MTB ICL with natural compounds; and (d) non-MTB ICL with synthetic compounds. Each of the approaches is capable of overcoming different challenges of inhibitor discovery. We hope that this paper will benefit the discovery of better inhibitor for ICL. PMID:25649791

Chemical Preparation Laboratory for IND Candidate Compounds

DTIC Science & Technology

1990-08-10

Confirmation by 500 MHz Spectroscopy of an Analogue of the Amaryllidaceae Alkaloids, Narciclasine and Pancratistatin." Bjarne Gabrielsen, Department...subdivided into modified nucleosides, alkaloids with synthetically modified precursors and analogues , and miscellaneous heterocycles that possess...or antitumor compounds were modified synthet 4cally to possibly yield novel analogues that possess enhanced activities or show a specific mode of

A synthetic cannabinoid FDU-NNEI, two 2H-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a phenethylamine derivative N-OH-EDMA, and a cathinone derivative dimethoxy-α-PHP, newly identified in illegal products.

PubMed

Uchiyama, Nahoko; Shimokawa, Yoshihiko; Kikura-Hanajiri, Ruri; Demizu, Yosuke; Goda, Yukihiro; Hakamatsuka, Takashi

Six new psychoactive substances were identified together with two other substances (compounds 1 - 8 ) in illegal products by our ongoing survey in Japan between January and July 2014. A new synthetic cannabinoid, FDU-NNEI [1-(4-fluorobenzyl)- N -(naphthalen-1-yl)-1 H -indole-3-carboxamide, 2 ], was detected with the newly distributed synthetic cannabinoid FDU-PB-22 ( 1 ). Two 2 H -indazole isomers of synthetic cannabinoids, AB-CHMINACA 2 H -indazole analog ( 3 ) and NNEI 2 H -indazole analog ( 4 ), were newly identified with 1 H -indazoles [AB-CHMINACA and NNEI indazole analog (MN-18)]. In addition, 2-methylpropyl N -(naphthalen-1-yl) carbamate ( 5 ) and isobutyl 1-pentyl-1 H -indazole-3-carboxylate ( 6 ) were detected in illegal products. Compound 6 is considered to be a by-product of the preparation of NNEI indazole analog from compound 5 and 1-pentyl-1 H -indazole. A phenethylamine derivative, N -OH-EDMA [ N -hydroxy-3,4-ethylenedioxy- N -methylamphetamine, 7 ], and a cathinone derivative, dimethoxy-α-PHP (dimethoxy-α-pyrrolidinohexanophenone, 8 ), were newly identified in illegal products. Among them, compounds 1 and 8 have been controlled as designated substances (Shitei-Yakubutsu) under the Pharmaceutical Affairs Law in Japan since August and November 2014, respectively.

Determination of endocrine disrupting compounds and their metabolites in fish bile.

PubMed

Ros, Oihana; Izaguirre, Jon Kepa; Olivares, Maitane; Bizarro, Cristina; Ortiz-Zarragoitia, Maren; Cajaraville, Miren Pilar; Etxebarria, Nestor; Prieto, Ailette; Vallejo, Asier

2015-12-01

This work describes a new methodology for the simultaneous determination of a large variety of emerging and persistent organic compounds and some of their metabolites in fish bile samples. The target compounds were musk fragrances, alkyl phenols, hormones, pesticides, phthalate esters and bisphenol-A, all of them with a known endocrine disrupting effect. To achieve the determination these three steps were optimized: i) an enzymatic hydrolysis of the metabolites to render the unconjugated compounds; ii) the solid phase extraction of the target analytes (Plexa cartridges 200-mg); and, iii) a clean-up of the extracts (Florisil cartridges 1-g). The samples were analyzed by gas-chromatography-mass spectrometry (GC-MS), though the polar fraction required a previous derivatization with O-bis (trimethylsilyl) trifluoroacetamide. Good apparent recoveries (63-122%), repeatability (<20%) and limits of detection (LODs) ranging between 0.04 and 459 ng/mL were obtained. This method was applied to the analysis of the target analytes in bile samples of thicklip grey mullets (Chelon labrosus) from five different populations of the Basque Coast (South East Bay of Biscay) during the period of May-June 2012. The target analytes were found at concentrations ranging from

Effects of habitat fragmentation on a stream-dwelling species, the flattened musk turtle Sternotherus depressus

USGS Publications Warehouse

Dodd, C.K.

1990-01-01

The flattened musk turtle Sternotherus depressus has disappeared from more than half of its former range because of habitat modifications to stream and river channels in the Warrior River Basin, Alabama. Only 6·9% of its probable historic range contains relatively healthy populations, and most populations are fragmented by extensive areas of unsuitable habitat. Turtles in the best remaining habitats continue to be vulnerable to disease and human-related disturbance, collecting and habitat modification. These factors lead to population declines and abnormal population structure. Habitat fragmentation, especially in small populations, increases vulnerability to human-caused catastrophes and demographic accidents, and could lead to eventual extinction. The threats facing fragmented populations of this turtle probably parallel those affecting many other stream-dwelling species throughout the southeastern United States.

Calculation methods to perform mass balances of micropollutants in sewage treatment plants. application to pharmaceutical and personal care products (PPCPs).

PubMed

Carballa, Marta; Omil, Francisco; Lema, Juan M

2007-02-01

Two different methods are proposed to perform the mass balance calculations of micropollutants in sewage treatment plants (STPs). The first method uses the measured data in both liquid and sludge phase and the second one uses the solid-water distribution coefficient (Kd) to calculate the concentrations in the sludge from those measured in the liquid phase. The proposed methodologies facilitate the identification of the main mechanisms involved in the elimination of micropollutants. Both methods are applied for determining mass balances of selected pharmaceutical and personal care products (PPCPs) and their results are discussed. In that way, the fate of 2 musks (galaxolide and tonalide), 3 pharmaceuticals (ibuprofen, naproxen, and sulfamethoxazole), and 2 natural estrogens (estrone and 17beta-estradiol) has been investigated along the different water and sludge treatment units of a STP. Ibuprofen, naproxen, and sulfamethoxazole are biologically degraded in the aeration tank (50-70%), while musks are equally sorbed to the sludge and degraded. In contrast, estrogens are not removed in the STP studied. About 40% of the initial load of pharmaceuticals passes through the plant unaltered, with the fraction associated to sludge lower than 0.5%. In contrast, between 20 and 40% of the initial load of musks leaves the plant associated to solids, with less than 10% present in the final effluent. The results obtained show that the conclusions concerning the efficiency of micropollutants removal in a particular STP may be seriously affected by the calculation method used.

Synthesis and antitumour activity of 4-aminoquinazoline derivatives

NASA Astrophysics Data System (ADS)

Lipunova, G. N.; Nosova, E. V.; Charushin, V. N.; Chupakhin, O. N.

2016-07-01

Pieces of data on the synthesis and antitumour activity of 4-aminoquinazolines are summarized and analyzed. Key methods for the synthesis of these compounds are considered, primarily cyclocondensation of carboxylic acid derivatives, as well as the oxidation of quinazolines and the cyclization of disubstituted thioureas. Improvements of synthetic schemes for erlotinib, gefitinib and lapatinib, which are the best-known pharmaceuticals based on compounds of the title class, are also considered. Synthetic strategies and biological activities for new 4-aminoquinazoline derivatives that are EGFR-tyrosine kinase inhibitors, multiactive compounds, and labelled compounds for use as positron emission tomography (PET) imaging agents are discussed. The bibliography includes 263 references.

Mimicking/extracting structure and functions of natural products: synthetic approaches that address unexplored needs in chemical biology.

PubMed

Hirai, Go

2015-04-01

Natural products are often attractive and challenging targets for synthetic chemists, and many have interesting biological activities. However, synthetic chemists need to be more than simply suppliers of compounds to biologists. Therefore, we have been seeking ways to actively apply organic synthetic methods to chemical biology studies of natural products and their activities. In this personal review, I would like to introduce our work on the development of new biologically active compounds inspired by, or extracted from, the structures of natural products, focusing on enhancement of functional activity and specificity and overcoming various drawbacks of the parent natural products. Copyright © 2014 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of 62 synthetic cannabinoids by gas chromatography-mass spectrometry with photoionization.

PubMed

Akutsu, Mamoru; Sugie, Ken-Ichi; Saito, Koichi

2017-01-01

Gas chromatography-mass spectrometry (GC-MS) in electron ionization (EI) mode is one of the most commonly used techniques for analysis of synthetic cannabinoids, because the GC-EI-MS spectra contain characteristic fragment ions for identification of a compound; however, the information on its molecular ions is frequently lacking. To obtain such molecular ion information, GC-MS in chemical ionization (CI) mode is frequently used. However, GC-CI-MS requires a relatively tedious process using reagent gas such as methane or isobutane. In this study, we show that GC-MS in photoionization (PI) mode provided molecular ions in all spectra of 62 synthetic cannabinoids, and 35 of the 62 compounds showed only the molecular radical cations. Except for the 35 compounds, the PI spectra showed very simple patterns with the molecular peak plus only a few fragment peak(s). An advantage is that the ion source for GC-PI-MS can easily be used for GC-EI-MS as well. Therefore, GC-EI/PI-MS will be a useful tool for the identification of synthetic cannabinoids contained in a dubious product. To the best of our knowledge, this is the first report to use GC-PI-MS for analysis of synthetic cannabinoids.

Mini-Review: Antifouling Natural Products from Marine Microorganisms and Their Synthetic Analogs

PubMed Central

Wu, Ze-Hong; Wang, Yu; Wang, Chang-Yun; Xu, Ying

2017-01-01

Biofouling causes huge economic loss and generates serious ecological issues worldwide. Marine coatings incorporated with antifouling (AF) compounds are the most common practices to prevent biofouling. With a ban of organotins and an increase in the restrictions regarding the use of other AF alternatives, exploring effective and environmentally friendly AF compounds has become an urgent demand for marine coating industries. Marine microorganisms, which have the largest biodiversity, represent a rich and important source of bioactive compounds and have many medical and industrial applications. This review summarizes 89 natural products from marine microorganisms and 13 of their synthetic analogs with AF EC50 values ≤ 25 μg/mL from 1995 (the first report about marine microorganism-derived AF compounds) to April 2017. Some compounds with the EC50 values < 5 μg/mL and LC50/EC50 ratios > 50 are highlighted as potential AF compounds, and the preliminary analysis of structure-relationship (SAR) of these compounds is also discussed briefly. In the last part, current challenges and future research perspectives are proposed based on opinions from many previous reviews. To provide clear guidance for the readers, the AF compounds from microorganisms and their synthetic analogs in this review are categorized into ten types, including fatty acids, lactones, terpenes, steroids, benzenoids, phenyl ethers, polyketides, alkaloids, nucleosides and peptides. In addition to the major AF compounds which targets macro-foulers, this review also includes compounds with antibiofilm activity since micro-foulers also contribute significantly to the biofouling communities. PMID:28846626

Mini-Review: Antifouling Natural Products from Marine Microorganisms and Their Synthetic Analogs.

PubMed

Wang, Kai-Ling; Wu, Ze-Hong; Wang, Yu; Wang, Chang-Yun; Xu, Ying

2017-08-28

Biofouling causes huge economic loss and generates serious ecological issues worldwide. Marine coatings incorporated with antifouling (AF) compounds are the most common practices to prevent biofouling. With a ban of organotins and an increase in the restrictions regarding the use of other AF alternatives, exploring effective and environmentally friendly AF compounds has become an urgent demand for marine coating industries. Marine microorganisms, which have the largest biodiversity, represent a rich and important source of bioactive compounds and have many medical and industrial applications. This review summarizes 89 natural products from marine microorganisms and 13 of their synthetic analogs with AF EC 50 values ≤ 25 μg/mL from 1995 (the first report about marine microorganism-derived AF compounds) to April 2017. Some compounds with the EC 50 values < 5 μg/mL and LC 50 /EC 50 ratios > 50 are highlighted as potential AF compounds, and the preliminary analysis of structure-relationship (SAR) of these compounds is also discussed briefly. In the last part, current challenges and future research perspectives are proposed based on opinions from many previous reviews. To provide clear guidance for the readers, the AF compounds from microorganisms and their synthetic analogs in this review are categorized into ten types, including fatty acids, lactones, terpenes, steroids, benzenoids, phenyl ethers, polyketides, alkaloids, nucleosides and peptides. In addition to the major AF compounds which targets macro-foulers, this review also includes compounds with antibiofilm activity since micro-foulers also contribute significantly to the biofouling communities.

Louisiana SIP: LAC 33:III Ch 21 Subchap J, 2147--Limiting Volatile Organic Compound (VOC) Emissions from Reactor Processes and Distillation Operations in Synthetic Organic Chemical manufacturing Industry (SOCMI); SIP effective 1998-02-02 (LAc74) to more..

EPA Pesticide Factsheets

Louisiana SIP: LAC 33:III Ch 21 Subchap J, 2147--Limiting Volatile Organic Compound (VOC) Emissions from Reactor Processes and Distillation Operations in Synthetic Organic Chemical manufacturing Industry (SOCMI); SIP effective 1998-02-02 (LAc74) more...

Louisiana SIP: LAC 33:III Ch 2147. Limiting Volatile Organic Compound (VOC) Emissions from Reactor Processes and Distillation Operations in Synthetic Organic Chemical manufacturing Industry (SOCMI); SIP effective 2011-08-04 (LAd34) to 2017-09-27

EPA Pesticide Factsheets

Louisiana SIP: LAC 33:III Ch 2147. Limiting Volatile Organic Compound (VOC) Emissions from Reactor Processes and Distillation Operations in Synthetic Organic Chemical manufacturing Industry (SOCMI); SIP effective 2011-08-04 (LAd34) to 2017-09-27

Recent Developments in Organophosphorus Flame Retardants Containing P-C Bond and Their Applications

PubMed Central

Wendels, Sophie; Chavez, Thiebault; Bonnet, Martin; Gaan, Sabyasachi

2017-01-01

Organophosphorus compounds containing P-C bonds are increasingly developed as flame retardant additives due to their excellent thermal and hydrolytic stability and ease of synthesis. The latest development (since 2010) in organophosphorus flame retardants containing P-C bonds summarized in this review. In this review, we have broadly classified such phosphorus compounds based on the carbon unit linked to the phosphorus atom i.e., could be a part of either an aliphatic or an aromatic unit. We have only considered those published literature where a P-C bond was created as a part of synthetic strategy to make either an intermediate or a final organophosphorus compound with an aim to use it as a flame retardant. General synthetic strategies to create P-C bonds are briefly discussed. Most popular synthetic strategies used for developing P-C containing phosphorus based flame retardants include Michael addition, Michaelis–Arbuzov, Friedels–Crafts and Grignard reactions. In general, most flame retardant derivatives discussed in this review have been prepared via a one- to two-step synthetic strategy with relatively high yields greater than 80%. Specific examples of P-C containing flame retardants synthesized via suitable synthetic strategy and their applications on various polymer systems are described in detail. Aliphatic phosphorus compounds being liquids or low melting solids are generally applied in polymers via coatings (cellulose) or are incorporated in the bulk of the polymers (epoxy, polyurethanes) during their polymerization as reactive or non-reactive additives. Substituents on the P atoms and the chemistry of the polymer matrix greatly influence the flame retardant behavior of these compounds (condensed phase vs. the gas phase). Recently, aromatic DOPO based phosphinate flame retardants have been developed with relatively higher thermal stabilities (>250 °C). Such compounds have potential as flame retardants for high temperature processable polymers such as polyesters and polyamides. A vast variety of P-C bond containing efficient flame retardants are being developed; however, further work in terms of their economical synthetic methods, detailed impact on mechanical properties and processability, long term durability and their toxicity and environmental impact is much needed for their potential commercial exploitations. PMID:28773147

Nephrotoxic effects of designer drugs: synthetic is not better!

PubMed

Luciano, Randy L; Perazella, Mark A

2014-06-01

Designer drugs are synthetic, psychoactive substances with similar structures and activity to existing scheduled drugs or controlled chemical compounds. The use of these drugs is not generally considered illegal and they cannot be detected using standard toxicology tests--essentially they are considered to be 'legal highs'. Over the past several years, increasing numbers of designer drugs have become available. These drugs are classified as amphetamine derivatives, phenylpiperazine derivatives, synthetic cathinones, synthetic cannabinoids, phencyclidine derivatives and synthetic opioids. Although euphoria is the desired effect, neuropsychiatric and cardiac manifestations are frequently observed in individuals using these drugs at high doses or using drugs that are contaminated with other substances. Some designer drugs are also associated with adverse renal effects, including acute kidney injury from pigment nephropathy, acute tubular necrosis, obstructive nephropathy and hyponatraemia. The misuse of these drugs should be recognized and clinicians made aware of the potential for acute nephrotoxicity as the health burden of these compounds increases.

Derivation of predicted no effect concentration (PNEC) for HHCB to terrestrial species (plants and invertebrates).

PubMed

Wang, Xiaonan; Liu, Zhengtao; Wang, Wanhua; Zhang, Cong; Chen, Lihong

2015-03-01

The 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(γ)-2-benzopyrane (HHCB) is a synthetic musk which is used as a fragrance in a variety of personal care products, and due to this it is widely spread in the environment. However, there is no paper dealing with the predicted no effect concentration (PNEC) for HHCB to terrestrial species using the species sensitivity distribution (SSD) method, mainly results from the shortage of species toxicity data of different taxonomic levels. In this study, toxicity data were obtained from 10 chronic toxicity tests using 10 terrestrial species (3 dicotyledonous plants, 5 monocotyledonous plants and 2 terrestrial invertebrates) from 3 Phyla and 9 Families. The PNEC of HHCB was derived using the SSD method. The result of present research showed that the dicotyledonous Solanum lycopersicum was the most sensitive plants to HHCB contamination. The PNEC ranged between 0.70 and 3.52 mg HHCB/kg when using the log-logistic SSD method. It is recommended to use toxicity data of different taxonomic levels for the development of PNEC values in terrestrial environment due to different species sensitivity. Copyright © 2014 Elsevier B.V. All rights reserved.

Trace analysis of 61 natural and synthetic progestins in river water and sewage effluents by ultra-high performance liquid chromatography-tandem mass spectrometry.

PubMed

Shen, Xiaoyan; Chang, Hong; Sun, Dezhi; Wang, Linxia; Wu, Fengchang

2018-04-15

A broad number of natural and synthetic progestins are widely used in human and veterinary therapies. Although progestins exhibit adverse effects in aquatic organisms, information about environmental occurrence and fate have been limited to several compounds, hampering the accuracy of risk assessments of the compounds. In this study, a selective and sensitive analytical method was established to simultaneously determine 19 natural and 42 synthetic progestins in environmental waters, and the synthetic progestins included 19-nortestosterone, 17α-hydroxyprogesterone and progesterone derivatives. All of the target compounds were effectively separated using an HSS T3 column, and the recoveries for effluent and river samples were 80-115% and 75-105%, respectively. The detection limits for the 61 analytes were in the range of 0.05-0.60 ng/L and 0.03-0.40 ng/L for the effluent and river samples, respectively. The developed method is applied to analyze the target progestogens in sewage effluent and river water samples from Beijing. The detected concentrations of natural progesterone metabolites (3α-hydroxy-5β-tetrahydroprogesterone) were up to 63 times higher than those of the parent compound. Of the three groups of synthetic progestins, the progesterone derivatives were detected for the first time and had the highest concentrations followed by the 19-nortestosterone and 17α-hydroxyprogesterone derivatives. In contrast to previous studies, the predominant derivative compounds of 19-nortestosterone were found to be 19-nortestosterone, gestodene and mifepristone, and those of 17α-hydroxyprogesterone were 6-epi-medroxy progesterone 17-acetate and melengestrol acetate. The toxicities and environmental risk of these emerging progestins deserves more attention in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

Inhibition of toxic actions of phospholipase A2 isolated & characterized from the Indian Banded Krait (Bungarus fasciatus) venom by synthetic herbal compounds

PubMed Central

Gomes, Antony; Bhattacharya, Shamik; Mukherjee, Sanghamitra; Inn-ho-Tsai; Gomes, Aparna

2012-01-01

Background & objectives: Phospholipase A2 (PLA2) is one of the major constituents of krait venom associated with several pathophysiological actions like myotoxicity, cardiotoxicity, neurotoxicity, etc. As there was no specific antiserum available against Bungarus fasciatus venom, this study was done with synthetic herbal compounds, anti PLA2 rabbit antiserum and commercial polyvalent snake venom antiserum to neutralize the PLA2 induced toxicities in experimental models. Methods: B. fasciatus venom phospholipase A2 fraction 38 (BF-38) was isolated by ion exchange chromatography, molecular weight was determined by mass spectrometry and its N terminal amino acid sequence was identified. Monospecific rabbit antiserum was raised against the PLA2 in presence of Freund complete adjuvant. The neutralization of PLA2 induced toxicities was done in in vitro and in in vivo models using synthetic herbal compounds, anti PLA2 rabbit antiserum and commercial polyvalent snake venom antiserum. Results: A toxic PLA2 (BF-38) was purified from the B. fasciatus venom by CM-cellulose and HPLC, of 13.17 kDa and a minor band of 7.3 kDa using ESI-MS. The 13.17 kDa PLA2 sequence was NLYQFKNMIQC. The 7.3 kDa toxin sequence was RKCLTKYSQDNES and was found to be <10 per cent w/w. Anti PLA2 rabbit antiserum produced faint precipitant band in immunogel diffusion and showed low titre value. The commercial polyvalent snake venom antiserum, anti PLA2 rabbit antiserum and the synthetic herbal compounds neutralized the PLA 2 induced toxicities at different intensities. Interpretation & conclusions: Our results suggested that synthetic herbal compound (BA) along with antiserum might provide effective protection against PLA2 induced toxicities of B. fasciatus venom. PMID:22885262

Capability of microalgae-based wastewater treatment systems to remove emerging organic contaminants: a pilot-scale study.

PubMed

Matamoros, Víctor; Gutiérrez, Raquel; Ferrer, Ivet; García, Joan; Bayona, Josep M

2015-05-15

The effect of hydraulic retention time (HRT) and seasonality on the removal efficiency of 26 organic microcontaminants from urban wastewater was studied in two pilot high-rate algal ponds (HRAPs). The targeted compounds included pharmaceuticals and personal care products, fire retardants, surfactants, anticorrosive agents, pesticides and plasticizers, among others. The pilot plant, which was fed at a surface loading rate of 7-29 g of COD m(-2)d(-1), consisted of a homogenisation tank and two parallel lines, each one with a primary settler and an HRAP with a surface area of 1.5 m(2) and a volume of 0.5 m(3). The two HRAPs were operated with different HRTs (4 and 8 d). The removal efficiency ranged from negligible removal to more than 90% depending on the compound. Microcontaminant removal efficiencies were enhanced during the warm season, while the HRT effect on microcontaminant removal was only noticeable in the cold season. Our results suggest that biodegradation and photodegradation are the most important removal pathways, whereas volatilization and sorption were solely achieved for hydrophobic compounds (log Kow>4) with a moderately high Henry's law constant values (11-12 Pa m(-3)mol(-1)) such as musk fragrances. Whereas acetaminophen, ibuprofen and oxybenzone presented ecotoxicological hazard quotients (HQs) higher than 1 in the influent wastewater samples, the HQs for the effluent water samples were always below 1. Copyright © 2015 Elsevier B.V. All rights reserved.

Experience with synthetic fluorinated fluid lubricants

NASA Technical Reports Server (NTRS)

Conley, Peter L.; Bohner, John J.

1990-01-01

Since the late 1970's, the wet lubricant of choice for space mechanisms has been one of the family of synthetic perfluoro polyalkylether (PFPE) compounds, namely Fomblin Z-25 (Bray-815Z) or DuPont's Krytox 143xx series. While offering the advantages of extremely low vapor pressures and wide temperature ranges, these oils and derived greases have a complex chemistry compared to the more familiar natural and synthetic hydrocarbons. Many aerospace companies have conducted test programs to characterize the behavior of these compounds in a space environment, resulting in a large body of hard knowledge as well as considerable space lore concerning the suitability of the lubricants for particular applications and techniques for successful application. The facts are summarized and a few myths about the compounds are dispelled, and some performance guidelines for the mechanism design engineer are provided.

Identification of Novel Synthetic Toll-like Receptor 2 Agonists by High Throughput Screening*

PubMed Central

Guan, Yue; Omueti-Ayoade, Katherine; Mutha, Sarita K.; Hergenrother, Paul J.; Tapping, Richard I.

2010-01-01

Toll-like receptors (TLRs) play a central role in host defense by inducing inflammatory and adaptive immune responses following infection. Drugs that target TLRs are of considerable interest as potential inflammatory regulators, vaccine adjuvants, and novel immunotherapeutics. TLR2, in cooperation with either TLR1 or TLR6, mediates responses to a wide variety of microbial products as well as products of host tissue damage. In an effort to understand the structural basis of TLR2 recognition and uncover novel TLR2 agonists, a synthetic chemical library of 24,000 compounds was screened using an IL-8-driven luciferase reporter in cells expressing these human receptors. The screening yielded several novel TLR2-dependent activators that utilize TLR1, TLR6, or both as co-receptors. These novel small molecule compounds are aromatic in nature and structurally unrelated to any known TLR2 agonists. The three most potent compounds do not exhibit synergistic activity, nor do they act as pseudoantagonists toward natural TLR2 activators. Interestingly, two of the compounds exhibit species specificity and are inactive toward murine peritoneal macrophages. Mutational analysis reveals that although the central extracellular region of TLR1 is required for stimulation, there are subtle differences in the mechanism of stimulation mediated by the synthetic compounds in comparison with natural lipoprotein agonists. The three most potent compounds activate cells in the nanomolar range and stimulate cytokine production from human peripheral blood monocytes. Our results confirm the utility of high throughput screens to uncover novel synthetic TLR2 agonists that may be of therapeutic benefit. PMID:20504771

76 FR 11075 - Schedules of Controlled Substances: Temporary Placement of Five Synthetic Cannabinoids Into...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-01

... of Abuse A ``cannabinoid'' is a class of chemical compounds in the marijuana plant that are... constituent of marijuana. ``Synthetic cannabinoids'' are a large family of chemically unrelated structures functionally (biologically) similar to THC, the active principle of marijuana. Two of the five synthetic...

Synthetic Fiber Production Facilities: New Source Performance Standards (NSPS)

EPA Pesticide Factsheets

These standards limits emissions of volatile organic compounds (VOC) from new and reconstructed synthetic fiber production facilities that use solvent-spinning processes. Includes rule history and summary.

KSC-2014-2184

NASA Image and Video Library

2014-04-18

CAPE CANAVERAL, Fla. - An image of SpaceX CEO and chief designer Elon Musk is displayed in the NASA Press Site news auditorium at Kennedy Space Center in Florida during a SpaceX-3 post-launch news conference. Musk participated in the conference by telephone. SpaceX-3 launched at 3:25 p.m. EDT aboard a Falcon 9 rocket carrying a Dragon capsule from Space Launch Complex 40 on Cape Canaveral Air Force Station. Dragon is making its fourth trip to the space station. The SpaceX-3 mission, carrying almost 2.5 tons of supplies, technology and science experiments, is the third of 12 flights through a $1.6 billion NASA Commercial Resupply Services contract. Dragon's cargo will support more than 150 experiments that will be conducted during the station's Expeditions 39 and 40. For more information, visit http://www.nasa.gov/mission_pages/station/structure/launch/index.html. Photo credit: NASA/Kim Shiflett

Autoantibody profile and clinical characteristics in a cohort of Chinese adult myasthenia gravis patients.

PubMed

Hong, Yu; Li, Hai-Feng; Skeie, Geir Olve; Romi, Fredrik; Hao, Hong-Jun; Zhang, Xu; Gao, Xiang; Owe, Jone Furlund; Gilhus, Nils Erik

2016-09-15

Myasthenia gravis (MG) is an autoimmune disorder with heterogeneity. Antibodies against acetylcholine receptor (AChR), muscle-specific kinase (MuSK), titin and ryanodine receptor (RyR) were examined in 437 adult Chinese MG patients. The AChR, MuSK, titin and RyR antibodies were found in 82.2%, 2.3%, 28.4% and 23.8% of all patients. Autoantibody profiles vary among different MG subgroups. Thymoma MG patients had high frequencies of AChR (99.2%), titin (50.8%) and RyR antibodies (46.9%). The titin and RyR antibodies also showed high frequencies in late onset patients (54.4% and 33.3%, respectively). These two antibodies may indicate an underlying thymoma when combined. The patients with titin and RyR antibodies tend to have more severe disease and worse outcome, and may need more active immunosuppressive treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute intoxication caused by synthetic cannabinoids 5F-ADB and MMB-2201: A case series.

PubMed

Barceló, Bernardino; Pichini, Simona; López-Corominas, Victoria; Gomila, Isabel; Yates, Christopher; Busardò, Francesco Paolo; Pellegrini, Manuela

2017-04-01

Synthetic cannabinoids are relatively new substances of abuse. Recently, abuse of synthetic cannabinoids has been increasingly reported in the lay press and medical literature. When new compounds are introduced, their use is initially not restricted by prohibition therefore their consumption cannot be verified by standard drug tests. The use of these compounds among adolescents and young adults is constantly growing, making it important for emergency services to be familiar with the signs and symptoms of intoxication present. Overdose and chronic use of these substances can cause adverse effects including altered mental status, tachycardia, and loss of consciousness. Here, we report five cases of acute intoxication by synthetic cannabinoids 5F-ADB and MMB-2201 with analytical confirmation. Copyright © 2017 Elsevier B.V. All rights reserved.

Semivolatile organic compounds in residential air along the Arizona - Mexico border

USGS Publications Warehouse

Gale, R.W.; Cranor, W.L.; Alvarez, D.A.; Huckins, J.N.; Petty, J.D.; Robertson, G.L.

2009-01-01

Concerns about indoor air quality and the potential effects on people living in these environments are increasing as more reports about the toxicities and the potential indoor air exposure levels of household-use chemicals and chemicals fromhousingandfurnishingmanufactureinairarebeingassessed. Gas chromatography/mass spectrometry was used to confirm numerous airborne contaminants obtained from the analysis of semipermeable membrane devices deployed inside of 52 homes situated along the border between Arizona and Mexico. We also describe nontarget analytes in the organochlorine pesticide fractions of 12 of these homes; this fraction is also the most likelytocontainthebroadestscopeofbioconcentratablechemicals accumulated from the indoor air. Approximately 400 individual components were identified, ranging from pesticides to a wide array of hydrocarbons, fragrances such as the musk xylenes, flavors relating to spices, aldehydes, alcohols, esters and phthalate esters, and other miscellaneous types of chemicals. The results presented in this study demonstrate unequivocally that the mixture of airborne chemicals present indoors is far more complex than previously demonstrated. ?? 2009 American Chemical Society.

Preclinical Testing of Novel Oxytocin Receptor Activators in Models of Autism Phenotypes

DTIC Science & Technology

2015-11-01

evaluated one synthetic oxytocin agonist, Compound 39, and one oxytocin metabolite, for efficacy against social deficits in BALB/cByJ mice, and we are...currently evaluating a second oxytocin metabolite for prosocial effects. Overall, we have successfully validated three mouse models as preclinical...to, first, prioritize synthetic compounds that activate the oxytocin receptor using cell-based assays, and secondly, evaluate the therapeutic efficacy

Synthetic cannabinoids: In silico prediction of the cannabinoid receptor 1 affinity by a quantitative structure-activity relationship model.

PubMed

Paulke, Alexander; Proschak, Ewgenij; Sommer, Kai; Achenbach, Janosch; Wunder, Cora; Toennes, Stefan W

2016-03-14

The number of new synthetic psychoactive compounds increase steadily. Among the group of these psychoactive compounds, the synthetic cannabinoids (SCBs) are most popular and serve as a substitute of herbal cannabis. More than 600 of these substances already exist. For some SCBs the in vitro cannabinoid receptor 1 (CB1) affinity is known, but for the majority it is unknown. A quantitative structure-activity relationship (QSAR) model was developed, which allows the determination of the SCBs affinity to CB1 (expressed as binding constant (Ki)) without reference substances. The chemically advance template search descriptor was used for vector representation of the compound structures. The similarity between two molecules was calculated using the Feature-Pair Distribution Similarity. The Ki values were calculated using the Inverse Distance Weighting method. The prediction model was validated using a cross validation procedure. The predicted Ki values of some new SCBs were in a range between 20 (considerably higher affinity to CB1 than THC) to 468 (considerably lower affinity to CB1 than THC). The present QSAR model can serve as a simple, fast and cheap tool to get a first hint of the biological activity of new synthetic cannabinoids or of other new psychoactive compounds. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Application of the Organic Synthetic Designs to Astrobiology

NASA Astrophysics Data System (ADS)

Kolb, V. M.

2009-12-01

In this paper we propose a synthesis of the heterocyclic compounds and the insoluble materials on the meteorites. Our synthetic scheme involves the reaction of sugars and amino acids, the so-called Maillard reaction. We have developed this scheme based on the combined analysis of the regular and retrosynthetic organic synthetic principles. The merits of these synthetic methods for the prebiotic design are addressed.

FORMATION OF NITRO MUSK ADDUCTS OF RAINBOW ...

EPA Pesticide Factsheets

The high use of nitro musk xylene (MX) and musk ketone (MK) as fragrances, and their persistence and bioaccumulation potential make them ubiquitous environmental contaminants. The 4-amino-MX (AMX) and 2-amino-MK (AMK) metabolites have been detected in trout fish hemoglobin (Hb) samples by gas chromatography-ion trap-mass spectrometry (GC-MS). Twelve Hb samples prepared from rainbow trout that were exposed to MX and MK, over a period of 24 and 72 h, were analyzed. Amino metabolites were liberated by basic hydrolysis and extracted from the fish Hb into n-hexane. The extract was concentrated, analyzed, and spiked with a standard solution (80 pg/uL) of AMX or AMK and reanalyzed. Concentrations of AMX from 10 to 24.7 ng/g were detected in Hb from fish taken 24 and 72 h after MX exposure. At 24 and 72 h after MK exposure, the concentration of AMK was found to be 25.1 to 51, and 9.5 to 25.1 ng/g, respectively. Concentrations of AMK in Hb from two of the three trout were substantially lower after 72 h compared with 24 h exposure. The AMX and AMK metabolites were not detected in four control samples. Average recoveries exceeding 89 and 86% could be achieved for AMX and AMK, respectively, with a coefficient of variation (CV) around 5%. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are the various r

Biochemical indicators of nephrotoxicity in blood serum of rats treated with novel 4-thiazolidinone derivatives or their complexes with polyethylene glycol-containing nanoscale polymeric carrier

PubMed

Kоbyli nska, L I; Havrylyuk, D Ya; Mitina, N E; Zaichenko, A S; Lesyk, R B; Zіme nkovsky, B S; Stoika, R S

2016-01-01

The aim of this study was to compare the effect of new synthetic 4-thiazolidinone derivatives (potential anticancer compounds denoted as 3882, 3288 and 3833) and doxorubicin (positive control) in free form and in their complexes with synthetic polyethylene glycol-containing nanoscale polymeric carrier on the biochemical indicators of nephrotoxicity in blood serum of rats. The concentration of total protein, urea, creatinine, glucose, ions of sodium, potassium, calcium, iron and chloride was measured. It was found that after injection of the investigated compounds, the concentration of sodium cations and chloride anions in blood serum was increased compared with control (untreated animals). Doxorubicin’s injection was accompanied by a decrease in the concentration of iron cations. The concentration of total protein, urea and creatinine decreased under the influence of the studied compounds. Complexation of these аntineoplastic substances with a synthetic polymeric nanocarrier lowered the concentration of the investigated metabolites substantially compared to the effect of these compounds in free form. The normalization of concentration of total protein, urea and creatinine in blood serum of rats treated with complexes of the studied compounds with the polymeric carrier comparing with increased concentration of these indicators at the introduction of such compounds in free form was found.

Organocatalyzed asymmetric alpha-oxidation, alpha-aminoxylation and alpha-amination of carbonyl compounds.

PubMed

Vilaivan, Tirayut; Bhanthumnavin, Worawan

2010-02-11

Organocatalytic asymmetric alpha-oxidation and amination reactions of carbonyl compounds are highly useful synthetic methodologies, especially in generating chiral building blocks that previously have not been easily accessible by traditional methods. The concept is relatively new and therefore the list of new catalysts, oxidizing and aminating reagents, as well as new substrates, are expanding at an amazing rate. The scope of this review includes new reactions and catalysts, mechanistic aspects and synthetic applications of alpha-oxidation, hydroxylation, aminoxylation, amination, hydrazination, hydroxyamination and related alpha-heteroatom functionalization of aldehydes, ketones and related active methylene compounds published during 2005-2009.

Novel synthetic organic compounds inspired from antifeedant marine alkaloids as potent bacterial biofilm inhibitors.

PubMed

Rane, Rajesh A; Karpoormath, Rajshekhar; Naphade, Shital S; Bangalore, Pavankumar; Shaikh, Mahamadhanif; Hampannavar, Girish

2015-08-01

In this paper, we have reported seventeen novel synthetic organic compounds derived from marine bromopyrrole alkaloids, exhibiting potential inhibition of biofilm produced by Gram-positive bacteria. Compound 5f with minimumbiofilm inhibitory concentration(MBIC) of 0.39, 0.78 and 3.125 μg/mL against MSSA, MRSA and SE respectively, emerged as promising anti-biofilm lead compounds. In addition, compounds 5b, 5c, 5d, 5e, 5f, 5h, 5i and 5j revealed equal potency as that of the standard drug Vancomycin (MBIC = 3.125 μg/mL) against Streptococcus epidermidis. Notably, most of the synthesized compounds displayed better potency than Vancomycin indicating their potential as inhibitors of bacterial biofilm. The cell viability assay for the most active hybrid confirms its anti-virulence properties which need to be further researched. Copyright © 2015 Elsevier Inc. All rights reserved.

Interspecific Responses of Termites to Synthetic Trail-Following Pheromones.

DTIC Science & Technology

Various synthetic analogs of the trail-following pheromone were tested against several subterranean and dry- and damp-wood termites . The synthetic... pheromones were found to be generally active against subterranean termites , both under laboratory and semi-field conditions. One of the most active compounds, 4-phenyl-cis-3-butanol, can be synthesized easily. (Author)

Polyborylated reagents for modern organic synthesis

PubMed Central

SHIMIZU, Masaki; HIYAMA, Tamejiro

2008-01-01

Diverse kinds of gem- and vic-diborylated compounds are now readily available thanks to advances in gem-diborylation of lithium carbenoids as well as vic-diborylation of carbon–carbon multiple bonds with diboron compounds. These diborylated reagents lead to invention of polyborylated reagents and many novel and useful synthetic methods for supreme stereocontrol. This review summarizes preparative methods and synthetic reactions of di- and polyborylated reagents with the emphasis on multiple bond formation. PMID:18941288

Evaluation of antimicrobial activity of extracts of Tibouchina candolleana (melastomataceae), isolated compounds and semi-synthetic derivatives against endodontic bacteria.

PubMed

Dos Santos, Fernanda M; de Souza, Maria Gorete; Crotti, Antônio E Miller; Martins, Carlos H G; Ambrósio, Sérgio R; Veneziani, Rodrigo C S; E Silva, Márcio L Andrade; Cunha, Wilson R

2012-04-01

This work describes the phytochemical study of the extracts from aerial parts of Tibouchina candolleana as well as the evaluation of the antimicrobial activity of extracts, isolated compounds, and semi-synthetic derivatives of ursolic acid against endodontic bacteria. HRGC analysis of the n-hexane extract of T. candolleana allowed identification of β-amyrin, α-amyrin, and β-sitosterol as major constituents. The triterpenes ursolic acid and oleanolic acid were isolated from the methylene chloride extract and identified. In addition, the flavonoids luteolin and genistein were isolated from the ethanol extract and identified. The antimicrobial activity was investigated via determination of the minimum inhibitory concentration (MIC) using the broth microdilution method. Amongst the isolated compounds, ursolic acid was the most effective against the selected endodontic bacteria. As for the semi-synthetic ursolic acid derivatives, only the methyl ester derivative potentiated the activity against Bacteroides fragilis.

Evaluation of antimicrobial activity of extracts of Tibouchina candolleana (melastomataceae), isolated compounds and semi-synthetic derivatives against endodontic bacteria

PubMed Central

dos Santos, Fernanda M.; de Souza, Maria Gorete; Crotti, Antônio E. Miller; Martins, Carlos H. G.; Ambrósio, Sérgio R.; Veneziani, Rodrigo C. S.; e Silva, Márcio L. Andrade; Cunha, Wilson R.

2012-01-01

This work describes the phytochemical study of the extracts from aerial parts of Tibouchina candolleana as well as the evaluation of the antimicrobial activity of extracts, isolated compounds, and semi-synthetic derivatives of ursolic acid against endodontic bacteria. HRGC analysis of the n-hexane extract of T. candolleana allowed identification of β-amyrin, α-amyrin, and β-sitosterol as major constituents. The triterpenes ursolic acid and oleanolic acid were isolated from the methylene chloride extract and identified. In addition, the flavonoids luteolin and genistein were isolated from the ethanol extract and identified. The antimicrobial activity was investigated via determination of the minimum inhibitory concentration (MIC) using the broth microdilution method. Amongst the isolated compounds, ursolic acid was the most effective against the selected endodontic bacteria. As for the semi-synthetic ursolic acid derivatives, only the methyl ester derivative potentiated the activity against Bacteroides fragilis. PMID:24031892

Antibiofilm potential of synthetic 2-amino-5-chlorobenzophenone Schiff bases and its confirmation through fluorescence microscopy.

PubMed

Arshia; Khan, Anum Khalid; Khan, Khalid Mohammed; Ahmed, Ayaz; Taha, Muhammad; Perveen, Shahnaz

2017-09-01

Antibacterial/antibiofilm potential of microwave-assisted synthetic thirty-three 2-amino-5-chloro benzophenone Schiff bases have been carried out against four bacterial strains i.e. Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus and Streptococcus mutans. Among them compounds 5, 6, 8, 9, 14, 16, 22, 24, 26, and 30-32 showed antibiofilm activities against isolates at less than 100 μg/ml concentrations. These compounds showed enhanced antibiofilm activity against S. aureus as compared to cefixime used as control. However, remaining compounds were found to be active but at higher concentration. Fluorescence microscopy has been employed for confirmation of antibiofilm results. The structures of all synthetic molecules have been characterized on the basis of spectroscopic techniques including 1 H NMR, 13 C NMR, EI-MS, HREI-MS, and IR spectroscopy and their structure-activity relationship have been established. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification and quantification of synthetic cannabinoids in "spice-like" herbal mixtures: Update of the German situation for the spring of 2016.

PubMed

Langer, Nico; Lindigkeit, Rainer; Schiebel, Hans-Martin; Papke, Uli; Ernst, Ludger; Beuerle, Till

2016-12-01

In February 2016, nine "spice-like" products from German language internet shops were analyzed. In total, eight different synthetic cannabinoids were identified by gas chromatography-mass spectrometry (GC-MS), namely THJ-018, THJ-2201, MAB-CHMINACA, 5F-ADB, 5Cl-AKB48 (syn.: 5C-AKB48), 4-pentenyl-AKB48, MDMB-CHMICA and 5F-AB-PINACA. For the majority of products only one synthetic cannabinoid was identified as the active ingredient, while two products contained 2 and 5 compounds, respectively. For some of the identified cannabinoids (MAB-CHMINACA, 5Cl-AKB48 and 4-pentenyl-AKB48) no or only insufficient physico-chemical data were available in literature. To our knowledge 5Cl-AKB48 and 4-pentenyl-AKB48 were found for the first time in commercially available products, hence an in-depth characterization of these compounds by NMR, EI-MS, ESI-MS/MS, IR- and UV spectroscopy was conducted. In addition, all synthetic cannabinoids were quantified by a GC-MS method using JWH-018 as internal standard and the corresponding response factors to calculate the total amount of all synthetic cannabinoids in the commercial smoking mixtures. The content of synthetic cannabinoids in the investigated products ranged from 23 to 120mg/g (average: 57mg/g), while individual compounds ranged from 1 to 120mg/g. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Metal Based Synthetic Strategies and the Examination of Structure Determining Factors in Alkaline Earth Metal Compounds

NASA Astrophysics Data System (ADS)

Takahashi, Yuriko

Last decades have witnessed a large expansion of the organometallic heavier alkaline earth metal species. However, continued growth of this promising area of chemistry has been slowed by severe restrictions and limitations in viable synthetic methodologies leading to difficulties in preparing and characterizing the target compounds. There is clearly a need for the further development of synthetic methodologies and detailed structure function analysis that will promote the further advancement of organoalkaline earth metal chemistry in applications as diverse as materials chemistry and catalysis. This thesis work greatly extends the synthetic options currently available towards organoalkaline earth metal species by introducing redox transmetallation protolysis (RTP), a reaction based on the readily available Ph3Bi as a non-toxic transmetallation agent. Based on a straightforward one-pot procedure and work-up, Ph3Bi based RTP presents a powerful synthetic alternative for the facile preparation of a large variety of heavy alkaline earth metal compounds. The second part of the thesis explores the effect of secondary non covalent interactions on the coordination chemistry as well as thermal properties of a series of novel alkali, alkaline earth, rare earth as well as heterobimetallic alkali/alkaline earth fluoroalkoxides. These compounds showcase the significance of non-covalent M···F-C and agostic interactions on metal stabilization and structural features, providing critical input on ligand design for the design of advanced metal organic vapor deposition (MOCVD) precursor materials. This work also showcases the impact of M···F-C interactions over M---co-ligand coordination, a critical precursor design element as well.

Using cheminformatics to predict cross reactivity of “designer drugs” to their currently available immunoassays

PubMed Central

2014-01-01

Background A challenge for drug of abuse testing is presented by ‘designer drugs’, compounds typically discovered by modifications of existing clinical drug classes such as amphetamines and cannabinoids. Drug of abuse screening immunoassays directed at amphetamine or methamphetamine only detect a small subset of designer amphetamine-like drugs, and those immunoassays designed for tetrahydrocannabinol metabolites generally do not cross-react with synthetic cannabinoids lacking the classic cannabinoid chemical backbone. This suggests complexity in understanding how to detect and identify whether a patient has taken a molecule of one class or another, impacting clinical care. Methods Cross-reactivity data from immunoassays specifically targeting designer amphetamine-like and synthetic cannabinoid drugs was collected from multiple published sources, and virtual chemical libraries for molecular similarity analysis were built. The virtual library for synthetic cannabinoid analysis contained a total of 169 structures, while the virtual library for amphetamine-type stimulants contained 288 compounds. Two-dimensional (2D) similarity for each test compound was compared to the target molecule of the immunoassay undergoing analysis. Results 2D similarity differentiated between cross-reactive and non-cross-reactive compounds for immunoassays targeting mephedrone/methcathinone, 3,4-methylenedioxypyrovalerone, benzylpiperazine, mephentermine, and synthetic cannabinoids. Conclusions In this study, we applied 2D molecular similarity analysis to the designer amphetamine-type stimulants and synthetic cannabinoids. Similarity calculations can be used to more efficiently decide which drugs and metabolites should be tested in cross-reactivity studies, as well as to design experiments and potentially predict antigens that would lead to immunoassays with cross reactivity for a broader array of designer drugs. PMID:24851137

Musk as a Pheromone? Didactic Exercise.

ERIC Educational Resources Information Center

Bersted, Chris T.

A classroom/laboratory exercise has been used to introduce college students to factorial research designs, differentiate between interpretations for experimental and quasi-experimental variables, and exemplify application of laboratory research methods to test practical questions (advertising claims). The exercise involves having randomly divided…

Tripping with Synthetic Cannabinoids ("Spice"): Anecdotal and Experimental Observations in Animals and Man.

PubMed

Järbe, Torbjörn U C; Raghav, Jimit Girish

2017-01-01

The phenomenon of consuming synthetic cannabinoids ("Spice") for recreational purposes is a fairly recent trend. However, consumption of cannabis dates back millennia, with numerous accounts written on the experience of its consumption, and thousands of scientific reports published on the effects of its constituents in laboratory animals and humans. Here, we focus on consolidating the scientific literature on the effects of "Spice" compounds in various behavioral assays, including assessing abuse liability, tolerance, dependence, withdrawal, and potential toxicity. In most cases, the behavioral effects of "Spice" compounds are compared with those of Δ 9 -tetrahydrocannabinol. Methodological aspects, such as modes of administration and other logistical issues, are also discussed. As the original "Spice" molecules never were intended for human consumption, scientifically based information about potential toxicity and short- and long-term behavioral effects are very limited. Consequently, preclinical behavioral studies with "Spice" compounds are still in a nascent stage. Research is needed to address the addiction potential and other effects, including propensity for producing tissue/organ toxicity, of these synthetic cannabimimetic "Spice" compounds.

Synthesis, in vitro β-glucuronidase inhibitory potential and molecular docking studies of quinolines.

PubMed

Bano, Bilquees; Arshia; Khan, Khalid Mohammed; Kanwal; Fatima, Bibi; Taha, Muhammad; Ismail, Nor Hadiani; Wadood, Abdul; Ghufran, Mehreen; Perveen, Shahnaz

2017-10-20

In this study synthesis and β-glucuronidase inhibitory potential of 3/5/8 sulfonamide and 8-sulfonate derivatives of quinoline (1-40) are discussed. Studies reveal that all the synthetic compounds were found to have good inhibitory activity against β-glucuronidase. Nonetheless, compounds 1, 2, 5, 13, and 22-24 having IC 50 values in the range of 1.60-8.40 μM showed superior activity than the standard saccharic acid 1,4-lactone (IC 50  = 48.4 ± 1.25 μM). Moreover, molecular docking studies of selected compounds were also performed to see interactions between active compounds and binding sites. Structures of all the synthetic compounds were confirmed through 1 H NMR, EI-MS and HREI-MS spectroscopic techniques. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Automated recycling of chemistry for virtual screening and library design.

PubMed

Vainio, Mikko J; Kogej, Thierry; Raubacher, Florian

2012-07-23

An early stage drug discovery project needs to identify a number of chemically diverse and attractive compounds. These hit compounds are typically found through high-throughput screening campaigns. The diversity of the chemical libraries used in screening is therefore important. In this study, we describe a virtual high-throughput screening system called Virtual Library. The system automatically "recycles" validated synthetic protocols and available starting materials to generate a large number of virtual compound libraries, and allows for fast searches in the generated libraries using a 2D fingerprint based screening method. Virtual Library links the returned virtual hit compounds back to experimental protocols to quickly assess the synthetic accessibility of the hits. The system can be used as an idea generator for library design to enrich the screening collection and to explore the structure-activity landscape around a specific active compound.

In vitro activity of synthetic tetrahydroindeno[2,1-c]quinolines on Leishmania mexicana.

PubMed

Hernández-Chinea, Concepción; Carbajo, Erika; Sojo, Felipe; Arvelo, Francisco; Kouznetsov, Vladimir V; Romero-Bohórquez, Arnold R; Romero, Pedro J

2015-12-01

New synthetic compounds based on tetrahydroindenoquinoline structure were evaluated for their in vitro antileishmanial activities. The seven compounds assayed have antiproliferative activities against promastigotes of Leishmania mexicana. Compound 1 and 3 were the most active (IC50 1.0 μg/ml) and showed high selectivity towards the parasite. These compounds were selected to evaluate their effect on promastigote morphology and mitochondrial transmembrane potential as well as on the amastigote capability to survive into macrophages J774 cell line. Whereas compound 1 affected the promastigote cell cycle, compound 3 induced morphological changes and the total collapse of the mitochondrial transmembrane potential, a hallmark of apoptosis. Both compounds also affected the amastigote form of the parasite, decreasing their survival rate in J774 macrophages. Due to the greatest selectivity index, the apparent effect as apoptotic inducer and its sustained inhibition on intracellular amastigote replication, compound 3 is the best candidate to be tested in vivo. This compound is worth considering for the development of new antileishmanial drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluating novel synthetic compounds active against Bacillus subtilis and Bacillus cereus spores using Live imaging with SporeTrackerX.

PubMed

Omardien, Soraya; Ter Beek, Alexander; Vischer, Norbert; Montijn, Roy; Schuren, Frank; Brul, Stanley

2018-06-14

An empirical approach was taken to screen a novel synthetic compound library designed to be active against Gram-positive bacteria. We obtained five compounds that were active against spores from the model organism Bacillus subtilis and the food-borne pathogen Bacillus cereus during our population based experiments. Using single cell live imaging we were able to observe effects of the compounds on spore germination and outgrowth. Difference in sensitivity to the compounds could be observed between B. subtilis and B. cereus using live imaging, with minor difference in the minimal inhibitory and bactericidal concentrations of the compounds against the spores. The compounds all delayed the bursting time of germinated spores and affected the generation time of vegetative cells at sub-inhibitory concentrations. At inhibitory concentrations spore outgrowth was prevented. One compound showed an unexpected potential for preventing spore germination at inhibitory concentrations, which merits further investigation. Our study shows the valuable role single cell live imaging can play in the final selection process of antimicrobial compounds.

Synthetic CO.sub.2 acceptor

DOEpatents

Lancet, Michael S.; Curran, George P.

1981-08-18

A synthetic CO.sub.2 acceptor consisting essentially of at least one compound selected from the group consisting of calcium oxide and calcium carbonate supported in a refractory carrier matrix, the carrier having the general formula Ca.sub.5 (SiO.sub.4).sub.2 CO.sub.3. A method for producing the synthetic CO.sub.2 acceptor is also disclosed.

Method for producing and regenerating a synthetic CO.sub.2 acceptor

DOEpatents

Lancet, Michael S [Pittsburgh, PA; Curran, George P [Pittsburgh, PA; Gorin, Everett [San Rafael, CA

1982-01-01

A method for producing a synthetic CO.sub.2 acceptor by feeding a mixture of finely divided silica and at least one finely divided calcium compound selected from the group consisting of calcium oxide and calcium carbonate to a fluidized bed; operating the fluidized bed at suitable conditions to produce pellets of synthetic CO.sub.2 acceptor and recovering the pellets of synthetic CO.sub.2 acceptor from the fluidized bed. Optionally, spent synthetic CO.sub.2 acceptor can be charged to the fluidized bed to produce regenerated pellets of synthetic CO.sub.2 acceptor.

Method for producing and regenerating a synthetic CO[sub 2] acceptor

DOEpatents

Lancet, M. S.; Curran, G. P.; Gorin, E.

1982-05-18

A method is described for producing a synthetic CO[sub 2] acceptor by feeding a mixture of finely divided silica and at least one finely divided calcium compound selected from the group consisting of calcium oxide and calcium carbonate to a fluidized bed; operating the fluidized bed at suitable conditions to produce pellets of synthetic CO[sub 2] acceptor and recovering the pellets of synthetic CO[sub 2] acceptor from the fluidized bed. Optionally, spent synthetic CO[sub 2] acceptor can be charged to the fluidized bed to produce regenerated pellets of synthetic CO[sub 2] acceptor. 1 fig.

Antileishmanial activity of the hydroalcoholic extract of Miconia langsdorffii, isolated compounds, and semi-synthetic derivatives.

PubMed

Peixoto, Juliana A; Andrade E Silva, Márcio Luis; Crotti, Antônio E M; Cassio Sola Veneziani, Rodrigo; Gimenez, Valéria M M; Januário, Ana H; Groppo, Milton; Magalhães, Lizandra G; Dos Santos, Fransérgio F; Albuquerque, Sérgio; da Silva Filho, Ademar A; Cunha, Wilson R

2011-02-22

The in vitro activity of the crude hydroalcoholic extract of the aerial parts of Miconia langsdorffii Cogn. was evaluated against the promastigote forms of L. amazonensis, the causative agent of cutaneous leishmaniasis in humans. The bioassay-guided fractionation of this extract led to identification of the triterpenes ursolic acid and oleanolic acid as the major compounds in the fraction that displayed the highest activity. Several ursolic acid semi-synthetic derivatives were prepared, to find out whether more active compounds could be obtained. Among these ursolic acid-derived substances, the C-28 methyl ester derivative exhibited the best antileishmanial activity.

Water-quality assessment of part of the upper Mississippi River basin, Minnesota and Wisconsin: Design and implementation of water-quality studies, 1995-98

USGS Publications Warehouse

Stark, James R.; Fallon, J.D.; Fong, A.L.; Goldstein, R.M.; Hanson, P.E.; Kroening, S.E.; Lee, K.E.

1999-01-01

This report describes the design, site-selection, and implementation of the study. Methods used to collect, process, and analyze samples; characterize sites; and assess habitat are described. A comprehensive list of sample sites is provided. Sample analyses for water-quality studies included chlorophyll a, major inorganic constituents, nutrients, trace elements, tritium, radon, environmental isotopes, organic carbon, pesticides, volatile organic compounds, and other synthetic and naturallyoccurring organic compounds. Aquatic-biological samples included fish, benthic macroinvertebrates, and algal enumeration and identification, as well as synthetic-organic compounds and trace elements in fish tissue.

Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015.

PubMed

Riederer, Anne M; Campleman, Sharan L; Carlson, Robert G; Boyer, Edward W; Manini, Alex F; Wax, Paul M; Brent, Jeffrey A

2016-07-15

Recent reports suggest that acute intoxications by synthetic cannabinoids are increasing in the United States (1,2). Synthetic cannabinoids, which were research compounds in the 1980s, are now produced overseas; the first shipment recognized to contain synthetic cannabinoids was seized at a U.S. border in 2008 (3). Fifteen synthetic cannabinoids are Schedule I controlled substances (3), but enforcement is hampered by the continual introduction of new chemical compounds (1,3). Studies of synthetic cannabinoids indicate higher cannabinoid receptor binding affinities, effects two to 100 times more potent than Δ(9)-tetrahydrocannabinol (the principal psychoactive constituent of cannabis), noncannabinoid receptor binding, and genotoxicity (4,5). Acute synthetic cannabinoid exposure reportedly causes a range of mild to severe neuropsychiatric, cardiovascular, renal, and other effects (4,6,7); chronic use might lead to psychosis (6,8). During 2010-2015, physicians in the Toxicology Investigators Consortium (ToxIC) treated 456 patients for synthetic cannabinoid intoxications; 277 of the 456 patients reported synthetic cannabinoids as the sole toxicologic agent. Among these 277 patients, the most common clinical signs of intoxication were neurologic (agitation, central nervous system depression/coma, and delirium/toxic psychosis). Relative to all cases logged by 50 different sites in the ToxIC Case Registry, there was a statistically significant association between reporting year and the annual proportion of synthetic cannabinoid cases. In 2015, reported cases of synthetic cannabinoid intoxication increased at several ToxIC sites, corroborating reported upward trends in the numbers of such cases (1,2) and underscoring the need for prevention.

[The possibility of using the synthetic compound for the purpose of modeling of the human soft tissues in connection with the evaluation of gunshot damages].

PubMed

Latyshov, I V; Vasil'ev, V A; Zaporotskova, I V; Ermakova, T A

The necessity of using a simulator of human soft tissues for the purpose of criminalistic and forensic medical expertises is dictated by the requirements put forward by the expert practice. The objective of the present study was to develop a synthetic simulator of the human soft tissues (compound) to ensure reliability of comparative criminalistics and forensic medical studies for the evaluation of gunshot injuries. The synthetic compound was prepared by mixing up the petroleum and/or synthetic oil with a polymeric thickening agent. This procedure was followed by heating the mixture at 90 degrees Celsius during 5 hours. Thereafter, petrolatum and/or ceresin and/or paraffin were added to the mixture. At the final stage, ionol was introduced, and the mixture was poured into a mold measuring 70×70×210 mm with its subsequent cooling down to 40 degrees Celsius during 10-12 hours. The experimental shooting was effected from the Kalashnikov AKS-74U assault rifle using the 5.45×39 mm (7H6) cartridges, Makarov pistol using the 9×18 mm cartridges and Nagant pistol using the CHELP-1000 cartridges. Five shots were fired from each of the three models. The experimental gunshot damages were evaluated visually by examining the inlet and exit openings and the bullet channel. In addition, criminalistic analysis of the grooves in cartridges was carried out. The technology for the fabrication of synthetic compounds based on ethylene, propylene, and butadiene co-polymers in the combination with such low molecular weight compounds as paraffins and ceresins having a homogeneous structure makes it possible to vary the rheological and mechanical properties of the simulators of human soft tissues for the solution of diagnostic and identification problems in the framework of criminalistics and forensic medical expertises.

Library Design-Facilitated High-Throughput Sequencing of Synthetic Peptide Libraries.

PubMed

Vinogradov, Alexander A; Gates, Zachary P; Zhang, Chi; Quartararo, Anthony J; Halloran, Kathryn H; Pentelute, Bradley L

2017-11-13

A methodology to achieve high-throughput de novo sequencing of synthetic peptide mixtures is reported. The approach leverages shotgun nanoliquid chromatography coupled with tandem mass spectrometry-based de novo sequencing of library mixtures (up to 2000 peptides) as well as automated data analysis protocols to filter away incorrect assignments, noise, and synthetic side-products. For increasing the confidence in the sequencing results, mass spectrometry-friendly library designs were developed that enabled unambiguous decoding of up to 600 peptide sequences per hour while maintaining greater than 85% sequence identification rates in most cases. The reliability of the reported decoding strategy was additionally confirmed by matching fragmentation spectra for select authentic peptides identified from library sequencing samples. The methods reported here are directly applicable to screening techniques that yield mixtures of active compounds, including particle sorting of one-bead one-compound libraries and affinity enrichment of synthetic library mixtures performed in solution.

A Reconnaissance of selected organic compounds in streams in tribal lands in Central Oklahoma, January-February 2009

USGS Publications Warehouse

Becker, Carol J.

2010-01-01

The U.S. Geological Survey worked in cooperation with the U.S. Environmental Protection Agency and the Kickapoo Tribe of Oklahoma on two separate reconnaissance projects carried out concurrently. Both projects entailed the use of passive samplers as a sampling methodology to investigate the detection of selected organic compounds at stream sites in jurisdictional areas of several tribes in central Oklahoma during January-February 2009. The focus of the project with the U.S. Environmental Protection Agency was the detection of pesticides and pesticide metabolites using Semipermeable Membrane Devices at five stream sites in jurisdictional areas of several tribes. The project with the Kickapoo Tribe of Oklahoma focused on the detection of pesticides, pesticide metabolites, polycyclic aromatic hydrocarbons, polychlorinated biphenyl compounds, and synthetic organic compounds using Semipermeable Membrane Devices and Polar Organic Chemical Integrative Samplers at two stream sites adjacent to the Kickapoo tribal lands. The seven stream sites were located in central Oklahoma on the Cimarron River, Little River, North Canadian River, Deep Fork, and Washita River. Extracts from SPMDs submerged at five stream sites, in cooperation with the U.S. Environmental Protection Agency, were analyzed for 46 pesticides and 6 pesticide metabolites. Dacthal, a pre-emergent herbicide, was detected at all five sites. Pendimethalin, also a pre-emergent, was detected at one site. The insecticides chlorpyrifos and dieldrin were detected at three sites and p,p'-DDE, a metabolite of the insecticide DDT, also was detected at three sites. SPMDs and POCIS were submerged at the upstream edge and downstream edge of the Kickapoo tribal boundaries. Both sites are downstream from the Oklahoma City metropolitan area and multiple municipal wastewater treatment plants. Extracts from the passive samplers were analyzed for 62 pesticides, 10 pesticide metabolites, 3 polychlorinated biphenyl compounds, 35 polycyclic aromatic hydrocarbons, and 49 synthetic organic compounds. Ten pesticides and four pesticide metabolites were detected at the upstream site and seven pesticides and four pesticide metabolites were detected at the downstream site. Pesticides detected at both sites were atrazine, chlorpyrifos, dacthal, dieldrin, metolachlor, pendimethalin, and trans-nonachlor. Additionally at the upstream site, heptachlor, pentachlorophenol, and prometon were detected. The pesticide metabolites p,p'-DDE, cis-chlordane, and trans-chlordane also were detected at both sites. Polychlorinated biphenyl compounds aroclor-1016/1242, aroclor-1254, and aroclor-1260 were detected at both sites. The upstream site had 16 polycyclic aromatic hydrocarbon detections and the downstream site had 8 detections. Because of chromatographic interference during analysis, a positive identification of 17 polycyclic aromatic hydrocarbons could not be made. Consequently, there may have been a greater number of these compounds detected at both sites. A total of 36 synthetic organic compounds were detected at the two sites adjacent to the Kickapoo tribal lands. The upstream site had 21 synthetic organic compound detections: three detergent metabolites, two fecal indicators, three flame retardants, seven industrial compounds, five compounds related to personal care products, and beta-sitosterol, a plant sterol. Fifteen synthetic organic compounds were detected at the downstream site and included: one fecal indicator, three flame retardants, six industrial compounds, and five compounds related to personal care products.

Inuloxins A-D and derivatives as antileishmanial agents: structure-activity relationship study

USDA-ARS?s Scientific Manuscript database

Inuloxins A-D (1-4) and a-costic acid (5), the phytotoxic compounds previously isolated from Inula viscosa, as well as synthetic derivatives of inuloxin A (compounds 6-10), inuloxin C (compound 11) and inuloxin D (compound 12) were tested in vitro for their activity against Leishmania donovani, the ...

Biological activity and molecular docking studies of curcumin-related α,β-unsaturated carbonyl-based synthetic compounds as anticancer agents and mushroom tyrosinase inhibitors.

PubMed

Bukhari, Syed Nasir Abbas; Jantan, Ibrahim; Unsal Tan, Oya; Sher, Muhammad; Naeem-Ul-Hassan, M; Qin, Hua-Li

2014-06-18

Hyperpigmentation in human skin and enzymatic browning in fruits, which are caused by tyrosinase enzyme, are not desirable. Investigations in the discovery of tyrosinase enzyme inhibitors and search for improved cytotoxic agents continue to be an important line in drug discovery and development. In present work, a new series of 30 compounds bearing α,β-unsaturated carbonyl moiety was designed and synthesized following curcumin as model. All compounds were evaluated for their effects on human cancer cell lines and mushroom tyrosinase enzyme. Moreover, the structure-activity relationships of these compounds are also explained. Molecular modeling studies of these new compounds were carried out to explore interactions with tyrosinase enzyme. Synthetic curcumin-like compounds (2a-b) were identified as potent anticancer agents with 81-82% cytotoxicity. Five of these newly synthesized compounds (1a, 8a-b, 10a-b) emerged to be the potent inhibitors of mushroom tyrosinase, providing further insight into designing compounds useful in fields of food, health, and agriculture.

Spirolactones: Recent Advances in Natural Products, Bioactive Compounds and Synthetic Strategies.

PubMed

Quintavalla, Arianna

2018-01-01

The spirocyclic compounds have always aroused a great interest because this motif is present as structural core in a number of natural products and bioactive compounds. In particular, the spirolactone moiety has been recognized in a wide array of natural and non-natural scaffolds showing a variety of useful pharmacological properties. Extensive literature search using SciFinder (Databases: CA Plus, CAS Registry, CAS React, Chemlist, Chemcat and Medline) and Web of Science (Database: Web of Science Core Collection) was conducted. Nowadays, many efforts are being devoted to the discovery of new natural products containing the promising spirolactone framework and to the disclosure of the potential bioactivities of these chemical entities. Moreover, the medicinal relevance of many spirolactones makes these scaffolds attractive targets for the design and development of innovative and efficient synthetic strategies, enabling the construction of complex and variably substituted products. This review gives an overview on the recent advances in the spirolactones field, in terms of new compounds isolated from natural sources, recently determined bioactivity profiles and innovative synthetic approaches. The collected data demonstrate the key role played by spirolactones in medicinal chemistry and the great attention still devoted by the scientific community to these compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Identification and analytical characterization of six synthetic cannabinoids NNL-3, 5F-NPB-22-7N, 5F-AKB-48-7N, 5F-EDMB-PINACA, EMB-FUBINACA, and EG-018.

PubMed

Liu, Cuimei; Jia, Wei; Hua, Zhendong; Qian, Zhenhua

2017-08-01

Clinical and forensic toxicology laboratories are continuously confronted by analytical challenges when dealing with the new psychoactive substances phenomenon. The number of synthetic cannabinoids, the chemical diversity, and the speed of emergence make this group of compounds particularly challenging in terms of detection, monitoring, and responding. Three indazole 7N positional isomer synthetic cannabinoids, two ethyl 2-amino-3-methylbutanoate-type synthetic cannabinoids, and one 9H-carbazole substituted synthetic cannabinoid were identified in seized materials. These six synthetic cannabinoid derivatives included: 1H-benzo[d] [1,2,3]triazol-1-yl 1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (NNL-3, 1), quinolin-8-yl 1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (5F-NPB-22-7N, 2), N-((1 s,3 s)-adamantan-1-yl)-1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide (5F-AKB-48-7N, 3), ethyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (5F-EDMB-PINACA, 4), ethyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoate (EMB-FUBINACA, 5), and naphthalen-1-yl(9-pentyl-9H-carbazol-3-yl)methanone (EG-018, 6). The identification was based on ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UHPLC-QTOF-MS), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance spectroscopy (NMR). The analytical characterization of these six synthetic cannabinoids was described, so as to assist forensic laboratories in identifying these compounds or other substances with similar structure in their case work. To our knowledge, no analytical data about the compounds 1-5 have appeared until now, making this the first report on these compounds. The GC-MS data of 6 has been reported, but this study added the LC-MS, NMR, and Fourier transform infrared (FTIR), data to render the analytical data collection process more complete. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Copper-Catalyzed Oxy-Alkynylation of Diazo Compounds with Hypervalent Iodine Reagents.

PubMed

Hari, Durga Prasad; Waser, Jerome

2016-02-24

Alkynes have found widespread applications in synthetic chemistry, biology, and materials sciences. In recent years, methods based on electrophilic alkynylation with hypervalent iodine reagents have made acetylene synthesis more flexible and efficient, but they lead to the formation of one equivalent of an iodoarene as side-product. Herein, a more efficient strategy involving a copper-catalyzed oxy-alkynylation of diazo compounds with ethynylbenziodoxol(on)e (EBX) reagents is described, which proceeds with generation of nitrogen gas as the only waste. This reaction is remarkable for its broad scope in both EBX reagents and diazo compounds. In addition, vinyl diazo compounds gave enynes selectively as single geometric isomers. The functional groups introduced during the transformation served as easy handles to access useful building blocks for synthetic and medicinal chemistry.

Antileishmanial activities of dihydrochalcones from piper elongatum and synthetic related compounds. Structural requirements for activity.

PubMed

Hermoso, Alicia; Jiménez, Ignacio A; Mamani, Zulma A; Bazzocchi, Isabel L; Piñero, José E; Ravelo, Angel G; Valladares, Basilio

2003-09-01

Two dihydrochalcones (1 and 2) were isolated from Piper elongatum Vahl by activity-guided fractionation against extracellular promastigotes of Leishmania braziliensis in vitro. Their structures were elucidated by spectral analysis, including homonuclear and heteronuclear correlation NMR experiments. Derivatives 3-7 and 20 synthetic related compounds (8-27) were also assayed to establish the structural requirements for antileishmanial activity. Compounds 1-11 that proved to be more active that ketoconazol, used as positive control, were further assayed against promastigotes of Leishmania tropica and Leishmania infantum. Compounds 7 and 11, with a C(6)-C(3)-C(6) system, proved to be the most promising compounds, with IC(50) values of 2.98 and 3.65 microg/mL, respectively, and exhibited no toxic effect on macrophages (around 90% viability). Correlation between the molecular structures and antileishmanial activity is discussed in detail.

Evaluation of first generation synthetic cannabinoids on binding at non-cannabinoid receptors and in a battery of in vivo assays in mice

PubMed Central

Wiley, Jenny L.; Lefever, Timothy W.; Marusich, Julie A.; Grabenauer, Megan; Moore, Katherine N.; Huffman, John W.; Thomas, Brian F.

2016-01-01

Anecdotal reports suggest that abused synthetic cannabinoids produce cannabis-like “highs,” but some of their effects may also differ from traditional cannabinoids such as Δ9-tetrahydrocannabinol (THC). This study examined the binding affinities of first-generation indole-derived synthetic cannabinoids at cannabinoid and noncannabinoid receptors and their effects in a functional observational battery (FOB) and drug discrimination in mice. All seven compounds, except JWH-391, had favorable affinity (≤ 159 nM) for both cannabinoid receptors. In contrast, binding at noncannabinoid receptors was absent or weak. In the FOB, THC and the six active compounds disrupted behaviors in CNS activation and muscle tone/equilibrium domains. Unlike THC, however, synthetic cannabinoids impaired behavior across a wider dose and domain range, producing autonomic effects and signs of CNS excitability and sensorimotor reactivity. In addition, mice acquired JWH-018 discrimination, and THC and JWH-073 produced full substitution whereas the 5-HT2B antagonist mianserin did not substitute in mice trained to discriminate JWH-018 or THC. Urinary metabolite analysis showed that the compounds were extensively metabolized, with metabolites that could contribute to their in vivo effects. Together, these results show that, while first-generation synthetic cannabinoids shared some effects that were similar to those of THC, they also possessed effects that differed from traditional cannabinoids. The high nanomolar (or absent) affinities of these compounds at receptors for most major neurotransmitters suggests that these divergent effects may be related to the greater potencies and/or efficacies at CB1 receptors; however, action(s) at noncannabinoid receptors yet to be assessed or via different signaling pathways cannot be ruled out. PMID:27449567

Evaluation of first generation synthetic cannabinoids on binding at non-cannabinoid receptors and in a battery of in vivo assays in mice.

PubMed

Wiley, Jenny L; Lefever, Timothy W; Marusich, Julie A; Grabenauer, Megan; Moore, Katherine N; Huffman, John W; Thomas, Brian F

2016-11-01

Anecdotal reports suggest that abused synthetic cannabinoids produce cannabis-like "highs," but some of their effects may also differ from traditional cannabinoids such as Δ(9)-tetrahydrocannabinol (THC). This study examined the binding affinities of first-generation indole-derived synthetic cannabinoids at cannabinoid and noncannabinoid receptors and their effects in a functional observational battery (FOB) and drug discrimination in mice. All seven compounds, except JWH-391, had favorable affinity (≤159 nM) for both cannabinoid receptors. In contrast, binding at noncannabinoid receptors was absent or weak. In the FOB, THC and the six active compounds disrupted behaviors in CNS activation and muscle tone/equilibrium domains. Unlike THC, however, synthetic cannabinoids impaired behavior across a wider dose and domain range, producing autonomic effects and signs of CNS excitability and sensorimotor reactivity. In addition, mice acquired JWH-018 discrimination, and THC and JWH-073 produced full substitution whereas the 5-HT2B antagonist mianserin did not substitute in mice trained to discriminate JWH-018 or THC. Urinary metabolite analysis showed that the compounds were extensively metabolized, with metabolites that could contribute to their in vivo effects. Together, these results show that, while first-generation synthetic cannabinoids shared some effects that were similar to those of THC, they also possessed effects that differed from traditional cannabinoids. The high nanomolar (or absent) affinities of these compounds at receptors for most major neurotransmitters suggests that these divergent effects may be related to the greater potencies and/or efficacies at CB1 receptors; however, action(s) at noncannabinoid receptors yet to be assessed or via different signaling pathways cannot be ruled out. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthetic cannabinoid JWH-018 and its halogenated derivatives JWH-018-Cl and JWH-018-Br impair Novel Object Recognition in mice: Behavioral, electrophysiological and neurochemical evidence.

PubMed

Barbieri, M; Ossato, A; Canazza, I; Trapella, C; Borelli, A C; Beggiato, S; Rimondo, C; Serpelloni, G; Ferraro, L; Marti, M

2016-10-01

It is well known that an impairment of learning and memory function is one of the major physiological effects caused by natural or synthetic cannabinoid consumption in rodents, nonhuman primates and in humans. JWH-018 and its halogenated derivatives (JWH-018-Cl and JWH-018-Br) are synthetic CB1/CB2 cannabinoid agonists, illegally marketed as "Spice" and "herbal blend" for their Cannabis-like psychoactive effects. In the present study the effects of acute exposure to JWH-018, JWH-018-Cl, JWH-018-Br (JWH-018-R compounds) and Δ(9)-THC (for comparison) on Novel Object Recognition test (NOR) has been investigated in mice. Moreover, to better characterize the effects of JWH-018-R compounds on memory function, in vitro electrophysiological and neurochemical studies in hippocampal preparations have been performed. JWH-018, JWH-018-Cl and JWH-018-Br dose-dependently impaired both short- and long-memory retention in mice (respectively 2 and 24 h after training session). Their effects resulted more potent respect to that evoked by Δ(9)-THC. Moreover, in vitro studies showed as JWH-018-R compounds negatively affected electrically evoked synaptic transmission, LTP and aminoacid (glutamate and GABA) release in hippocampal slices. Behavioral, electrophysiological and neurochemical effects were fully prevented by CB1 receptor antagonist AM251 pretreatment, suggesting a CB1 receptor involvement. These data support the hypothesis that synthetic JWH-018-R compounds, as Δ(9)-THC, impair cognitive function in mice by interfering with hippocampal synaptic transmission and memory mechanisms. This data outline the danger that the use and/or abuse of these synthetic cannabinoids may represent for the cognitive process in human consumer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is anaerobic digestion effective for the removal of organic micropollutants and biological activities from sewage sludge?

PubMed

Gonzalez-Gil, L; Papa, M; Feretti, D; Ceretti, E; Mazzoleni, G; Steimberg, N; Pedrazzani, R; Bertanza, G; Lema, J M; Carballa, M

2016-10-01

The occurrence of emerging organic micropollutants (OMPs) in sewage sludge has been widely reported; nevertheless, their fate during sludge treatment remains unclear. The objective of this work was to study the fate of OMPs during mesophilic and thermophilic anaerobic digestion (AD), the most common processes used for sludge stabilization, by using raw sewage sludge without spiking OMPs. Moreover, the results of analytical chemistry were complemented with biological assays in order to verify the possible adverse effects (estrogenic and genotoxic) on the environment and human health in view of an agricultural (re)use of digested sludge. Musk fragrances (AHTN, HHCB), ibuprofen (IBP) and triclosan (TCS) were the most abundant compounds detected in sewage sludge. In general, the efficiency of the AD process was not dependent on operational parameters but compound-specific: some OMPs were highly biotransformed (e.g. sulfamethoxazole and naproxen), while others were only slightly affected (e.g. IBP and TCS) or even unaltered (e.g. AHTN and HHCB). The MCF-7 assay evidenced that estrogenicity removal was driven by temperature. The Ames test did not show point mutation in Salmonella typhimurium while the Comet test exhibited a genotoxic effect on human leukocytes attenuated by AD. This study highlights the importance of combining chemical analysis and biological activities in order to establish appropriate operational strategies for a safer disposal of sewage sludge. Actually, it was demonstrated that temperature has an insignificant effect on the disappearance of the parent compounds while it is crucial to decrease estrogenicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Block by Block: Civic Action in the Battle of Baghdad

DTIC Science & Technology

2007-11-01

powdered musk and ambergris. Arts and sciences flourished— literature, music, calligraphy, philosophy, mathematics, chemistry, history. All that was...of the insur- gency, (i.e., guerrilla, underground, and auxiliary). The basic premise of civic-action operations is that the lower ech- elon of

TSCA Work Plan Chemical Risk Assessment HHCB 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-g-2- benzopyran

EPA Pesticide Factsheets

HHCB is one of the most widely used polycyclic musk fragrance ingredients in a range of consumer products including perfumes, cosmetics, shampoos, lotions, detergents, fabric softeners, and household cleaners.

Blood transcriptomics of captive forest musk deer (Moschus berezovskii) and possible associations with the immune response to abscesses.

PubMed

Sun, Xiaoning; Cai, Ruibo; Jin, Xuelin; Shafer, Aaron B A; Hu, Xiaolong; Yang, Shuang; Li, Yimeng; Qi, Lei; Liu, Shuqiang; Hu, Defu

2018-01-12

Forest musk deer (Moschus berezovskii; FMD) are both economically valuable and highly endangered. A problem for FMD captive breeding programs has been the susceptibility of FMD to abscesses. To investigate the mechanisms of abscess development in FMD, the blood transcriptomes of three purulent and three healthy individuals were generated. A total of ~39.68 Gb bases were generated using Illumina HiSeq 4000 sequencing technology and 77,752 unigenes were identified after assembling. All the unigenes were annotated, with 63,531 (81.71%) mapping to at least one database. Based on these functional annotations, 45,798 coding sequences (CDS) were detected, along with 12,697 simple sequence repeats (SSRs) and 65,536 single nucleotide polymorphisms (SNPs). A total of 113 unigenes were found to be differentially expressed between healthy and purulent individuals. Functional annotation indicated that most of these differentially expressed genes were involved in the regulation of immune system processes, particularly those associated with parasitic and bacterial infection pathways.

Species-specific responses of Late Quaternary megafauna to climate and humans

PubMed Central

Lorenzen, Eline D.; Nogués-Bravo, David; Orlando, Ludovic; Weinstock, Jaco; Binladen, Jonas; Marske, Katharine A.; Ugan, Andrew; Borregaard, Michael K.; Gilbert, M. Thomas P.; Nielsen, Rasmus; Ho, Simon Y. W.; Goebel, Ted; Graf, Kelly E.; Byers, David; Stenderup, Jesper T.; Rasmussen, Morten; Campos, Paula F.; Leonard, Jennifer A.; Koepfli, Klaus-Peter; Froese, Duane; Zazula, Grant; Stafford, Thomas W.; Aaris-Sørensen, Kim; Batra, Persaram; Haywood, Alan M.; Singarayer, Joy S.; Valdes, Paul J.; Boeskorov, Gennady; Burns, James A.; Davydov, Sergey P.; Haile, James; Jenkins, Dennis L.; Kosintsev, Pavel; Kuznetsova, Tatyana; Lai, Xulong; Martin, Larry D.; McDonald, H. Gregory; Mol, Dick; Meldgaard, Morten; Munch, Kasper; Stephan, Elisabeth; Sablin, Mikhail; Sommer, Robert S.; Sipko, Taras; Scott, Eric; Suchard, Marc A.; Tikhonov, Alexei; Willerslev, Rane; Wayne, Robert K.; Cooper, Alan; Hofreiter, Michael; Sher, Andrei; Shapiro, Beth; Rahbek, Carsten; Willerslev, Eske

2014-01-01

Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary remain contentious. We use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, underscoring the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change. PMID:22048313

Kiwifruit Flower Odor Perception and Recognition by Honey Bees, Apis mellifera.

PubMed

Twidle, Andrew M; Mas, Flore; Harper, Aimee R; Horner, Rachael M; Welsh, Taylor J; Suckling, David M

2015-06-17

Volatile organic compounds (VOCs) from male and female kiwifruit (Actinidia deliciosa 'Hayward') flowers were collected by dynamic headspace sampling. Honey bee (Apis mellifera) perception of the flower VOCs was tested using gas chromatography coupled to electroantennogram detection. Honey bees consistently responded to six compounds present in the headspace of female kiwifruit flowers and five compounds in the headspace of male flowers. Analysis of the floral volatiles by gas chromatography-mass spectrometry and microscale chemical derivatization showed the compounds to be nonanal, 2-phenylethanol, 4-oxoisophorone, (3E,6E)-α-farnesene, (6Z,9Z)-heptadecadiene, and (8Z)-heptadecene. Bees were then trained via olfactory conditioning of the proboscis extension response (PER) to synthetic mixtures of these compounds using the ratios present in each flower type. Honey bees trained to the synthetic mixtures showed a high response to the natural floral extracts, indicating that these may be the key compounds for honey bee perception of kiwifruit flower odor.

Bactericidal activity of glutaraldehyde-like compounds from olive products.

PubMed

Medina, Eduardo; Brenes, Manuel; García, Aranzazu; Romero, Concepción; de Castro, Antonio

2009-12-01

The bactericidal effects of several olive compounds (nonenal, oleuropein, tyrosol, the dialdehydic form of decarboxymethyl elenolic acid either free [EDA] or linked to tyrosol [TyEDA] or to hydroxytyrosol [HyEDA]), other food phenolic compounds (catechin, epicatechin, eugenol, thymol, carvacrol, and carnosic acid), and commercial disinfectants (glutaraldehyde [GTA] and ortho-phthalaldehyde [OPA]), were tested against strains of Pseudomonas fluorescens, Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli. It was found that the bactericidal activities of olive GTA-like compounds (EDA, HyEDA, and TyEDA) were greater than those exerted by several food phenolic substances. Surprisingly, these olive antimicrobials were as active as the synthetic biocides GTA and OPA against the four bacteria studied. Thus, it has been proposed that the bactericidal activity of the main olive antimicrobials is primarily due to their dialdehydic structure, which is similar to that of the commercial biocides GTA and OPA. Our results clearly reveal that olive GTA-like compounds possess a strong bactericidal activity even greater than that of other food phenolic compounds or synthetic biocides.

Synthetic routes to 3(5)-phosphonylated pyrazoles

NASA Astrophysics Data System (ADS)

Goulioukina, N. S.; Makukhin, N. N.; Beletskaya, I. P.

2016-07-01

This review comprehensively covers the currently available synthetic routes to 3(5)-phosphonylated pyrazoles. There are demonstrated significant advances in this field over the last 10-15 years caused by the use of the Bestmann-Ohira reagent [as well as (diazomethyl)phosphonates and phosphonylated hydrazonoyl halides] in reactions with diverse dipolarophiles. 1,3-Dipolar cycloaddition of diazo compounds to α,β-unsaturated phosphonates as well as intramolecular heterocyclization of (1-diazoallyl)phosphonates and (3--diazo-1-propenyl)phosphonates are discussed. Synthetic potential of cyclocondensation of organophosphorus 1,3-dielectrophilic compounds with hydrazines is shown. Ways to introduce a phosphonate group into the pyrazole ring are considered. Examples of chemical transformations of 3(5)-phosphonylated pyrazoles are reported. The bibliography includes 88 references.

Antifungal activity of synthetic antiseptics and natural compounds against Candida dubliniensis before and after in vitro fluconazole exposure.

PubMed

Reginato, Cássia Franco; Bandeira, Laíssa Arévalo; Zanette, Régis Adriel; Santurio, Janio Morais; Alves, Sydney Hartz; Danesi, Cristiane Cademartori

2017-01-01

This study evaluated the susceptibilities of oral candidiasis-derived Candida albicans, fluconazole-resistant (FR) Candida dubliniensis, and fluconazole-susceptible (FS) C. dubliniensis to synthetic antiseptics [chlorhexidine gluconate (CHX), cetylpyridinium chloride (CPC), and triclosan (TRC)] and natural compounds (carvacrol, eugenol and thymol). Susceptibility tests were performed based on the M27-A3 reference method. The fluconazole-resistant C. dubliniensis strains were obtained after prolonged in vitro exposure to increasing fluconazole concentrations. The geometric mean values for minimum inhibitory concentrations and minimum fungicidal concentrations were compared among the groups. Fluconazole-susceptible C. dubliniensis was more sensitive to CPC and TRC than FR C. dubliniensis and C. albicans were. However, eugenol and thymol were more active against FR C. dubliniensis. The fungicidal activities of CHX and TRC were similar for the three groups, and FR C. dubliniensis and C. albicans had similar sensitivities to CPC. The resistance of C. dubliniensis to fluconazole affects its sensitivity the synthetic antiseptics and natural compounds that were tested.

Strategies for the inhibition of gingipains for the potential treatment of periodontitis and associated systemic diseases

PubMed Central

Olsen, Ingar; Potempa, Jan

2014-01-01

Gingipains are the major virulence factors of Porphyromonas gingivalis, the main periodontopathogen. It is expected that inhibition of gingipain activity in vivo could prevent or slow down the progression of adult periodontitis. To date, several classes of gingipain inhibitors have been recognized. These include gingipain N-terminal prodomains, synthetic compounds, inhibitors from natural sources, antibiotics, antiseptics, antibodies, and bacteria. Several synthetic compounds are potent gingipain inhibitors but inhibit a broad spectrum of host proteases and have undesirable side effects. Synthetic compounds with high specificity for gingipains have unknown toxicity effects, making natural inhibitors more promising as therapeutic gingipain blockers. Cranberry and rice extracts interfere with gingipain activity and prevent the growth and biofilm formation of periodontopathogens. Although the ideal gingipain inhibitor has yet to be discovered, gingipain inhibition represents a novel approach to treat and prevent periodontitis. Gingipain inhibitors may also help treat systemic disorders that are associated with periodontitis, including cardiovascular disease, rheumatoid arthritis, aspiration pneumonia, pre-term birth, and low birth weight. PMID:25206939

Assessment of types of synthetic cannabinoids in narcotic cases assessed by the Council of Forensic Medicine between 2011-2015, Ankara, Turkey.

PubMed

Göl, Ersin; Çok, İsmet

2017-11-01

Synthetic cannabinoids mimic the effects of cannabis and are the largest and fastest growing class of newly appearing designer drugs. Reports have revealed that various types of synthetic cannabinoids are mixed with herbal substances. The present study investigated the herbal substance cases involving synthetic cannabinoids in Ankara and nearby cities in Turkey. Data were collected from the reports of synthetic cannabinoids that were analyzed between January 01, 2011 and December 31, 2015 in the Ankara Narcotic Department of the Council of Forensic Medicine at the request of the judicial authorities. In all, 4610 narcotic reports were obtained and reviewed. Among these narcotic reports during the period, 370 reports (8%) were related to synthetic cannabinoids. 28 synthetic cannabinoid compounds could be identified in herbals: 5-F-AB-PINACA, 5-F-AKB-48, 5-F-NNEI, 5-F-PB-22, AB-CHMINACA, AB-FUBINACA, AB-PINACA, ADB-CHMINACA, ADB-FUBINACA, AKB-48, AM-2201, EAM-2201, JWH-018, JWH-022, JWH-031, JWH-122, JWH-201, JWH-210, JWH-250, JWH-251, JWH-307, MAM-2201, NM-2201, PB-22, RCS-4, THJ-2201, UR-144, XLR-11. The amount of herbals was 30.72g, 329.22g, 665.89g, 4844.7g, and 5684.3g in 2011, 2012, 2013, 2014, and 2015, respectively. Generally, herbals contained more than one synthetic cannabinoids. ADB-FUBINACA was the most common synthetic cannabinoid among the herbals determined in this study, which was 3132.43g, excepting multi-synthetic cannabinoid herbals. The amount and diversity of synthetic cannabinoid compounds have increased dramatically between 2011 and 2015. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis of Methyl Diantilis, a Commercially Important Fragrance

ERIC Educational Resources Information Center

Miles, William H.; Connell, Katelyn B.

2006-01-01

Synthetic sequences in the undergraduate organic chemistry laboratory illustrate important synthetic strategies, reagents, or experimental techniques, oftentimes resulting in the synthesis of commercially important compounds. A fragrance with a 'spicy, carnation, sweet, vanilla', named after carnations (Dianthus caryophllus), Methyl Diantillis is…

Biological Activity of Peanut (Arachis hypogaea) Phytoalexins and Selected Natural and Synthetic Stilbenoids

PubMed Central

SOBOLEV, VICTOR S.; KHAN, SHABANA I.; TABANCA, NURHAYAT; WEDGE, DAVID E.; MANLY, SUSAN P.; CUTLER, STEPHEN J.; COY, MONIQUE R.; BECNEL, JAMES J.; NEFF, SCOTT A.; GLOER, JAMES B.

2011-01-01

The peanut plant (Arachis hypogaea L.), when infected by a microbial pathogen, is capable of producing stilbene-derived compounds that are considered antifungal phytoalexins. In addition, the potential health benefits of other stilbenoids from peanuts, including resveratrol and pterostilbene, have been acknowledged by several investigators. Despite considerable progress in peanut research, relatively little is known about the biological activity of the stilbenoid phytoalexins. This study investigated the activities of some of these compounds in a broad spectrum of biological assays. Since peanut stilbenoids appear to play roles in plant defense mechanisms, they were evaluated for their effects on economically important plant pathogenic fungi of the genera Colletotrichum, Botrytis, Fusarium, and Phomopsis. We further investigated these peanut phytoalexins, together with some related natural and synthetic stilbenoids (a total of 24 compounds) in a panel of bioassays to determine their anti-inflammatory, cytotoxic, and antioxidant activities in mammalian cells. Several of these compounds were also evaluated as mammalian opioid receptor competitive antagonists. Assays for adult mosquito and larvae toxicity were also performed. The results of these studies reveal that peanut stilbenoids, as well as related natural and synthetic stilbene derivatives, display a diverse range of biological activities. PMID:21314127

Attraction of Chrysoperla carnea complex and Chrysopa spp. lacewings (Neuroptera: Chrysopidae) to aphid sex pheromone components and a synthetic blend of floral compounds in Hungary.

PubMed

Koczor, Sándor; Szentkirályi, Ferenc; Birkett, Michael A; Pickett, John A; Voigt, Erzsébet; Tóth, Miklós

2010-12-01

The deployment of synthetic attractants for the manipulation of lacewing populations as aphid predators is currently used in integrated pest management. This study investigates a synthetic bait comprising floral compounds previously found to attract the Chrysoperla carnea complex, and, for the first time, the aphid sex pheromone components (1R,4aS,7S,7aR)-nepetalactol and (4aS,7S,7aR)-nepetalactone, in field experiments in Hungary, for their ability to manipulate lacewing populations. The synthetic floral bait attracted both sexes of the Chrysoperla carnea complex, and Chrysopa formosa Brauer showed minimal attraction. The aphid sex pheromone compounds alone attracted males of C. formosa and C. pallens (Rambur). When the two baits were combined, Chrysopa catches were similar to those with aphid sex pheromone baits alone, but carnea complex catches decreased significantly (by 85-88%). As the floral bait alone attracted both sexes of the carnea complex, it showed potential to manipulate the location of larval density via altering the site of oviposition. Aphid sex pheromone compounds alone attracted predatory males of Chrysopa spp. and can potentially be used to enhance biological control of aphids. For the carnea complex, however, a combination of both baits is not advantageous because of the decrease in adults attracted. Assumptions of intraguild avoidance underlying this phenomenon are discussed. Copyright © 2010 Society of Chemical Industry.

Triterpene derivatives as inhibitors of protein involved in the inflammatory process: molecules interfering with phospholipase A2, cycloxygenase, and lipoxygenase.

PubMed

Braca, Alessandra; Dal Piaz, Fabrizio; Marzocco, Stefania; Autore, Giuseppina; Vassallo, Antonio; De Tommasi, Nunziatina

2011-03-01

Over the past years, there was an explosion in the knowledge of the protein target and molecular mechanism associated with various disease types and in the new research of drugs of natural origin. The key idea is to evaluate bioactive natural products interacting with protein domains of different genetic origin but structurally preserved to develop libraries of compounds biologically validated and selected from an evolutionistic point of view. Compared with synthetic compounds, natural products have a major number of unused scaffolds and not comparable to the libraries of synthetic compounds, and could represent a promising starting points for the discovery of new bioactive compounds. Many natural products are reported to interact with proteins involved in serious diseases, such as inflammation and cancer. Recently various chemical classes of plant secondary metabolites have emerged as potential therapeutic compounds in several inflammatory diseases. Owing to the findings that triterpenoids, a common class of plant secondary metabolites, have anti-inflammatory and anti-cancer effects on humans, the interest in their potential application in human health and disease is increasing. The present review describes anti-inflammatory triterpenes derivatives from plant and fungi reported during the last two decades in order to provide an account of this field of investigation, sorting compounds according to their targets, phospholipase A(2) (PLA(2)), cycloxygenase (COX), and lipoxygenase (LOX). The attempt is also being made to enumerate the possible leads for further synthetic and drug discovery program development.

Synthetic algae and cyanobacteria: Great potential but what is the exposure risk?

EPA Science Inventory

Green algae and cyanobacteria (hereafter, algae) have the attractive properties of relatively simple genomes, rapid growth rates, and an ability to synthesize useful compounds using solar energy and carbon dioxide. They are attractive targets for applications of synthetic biology...

Comprehensive two-dimensional gas chromatography for the analysis of synthetic and crude-derived jet fuels.

PubMed

van der Westhuizen, Rina; Ajam, Mariam; De Coning, Piet; Beens, Jan; de Villiers, André; Sandra, Pat

2011-07-15

Fully synthetic jet fuel (FSJF) produced via Fischer-Tropsch (FT) technology was recently approved by the international aviation fuel authorities. To receive approval, comparison of FSJF and crude-derived fuel and blends on their qualitative and quantitative hydrocarbon composition was of utmost importance. This was performed by comprehensive two-dimensional gas chromatography (GC×GC) in the reversed phase mode. The hydrocarbon composition of synthetic and crude-derived jet fuels is very similar and all compounds detected in the synthetic product are also present in crude-derived fuels. Quantitatively, the synthetic fuel consists of a higher degree of aliphatic branching with less than half the aromatic content of the crude-derived fuel. GC×GC analyses also indicated the presence of trace levels of hetero-atomic impurities in the crude-derived product that were absent in the synthetic product. While clay-treatment removed some of the impurities and improved the fuel stability, the crude-derived product still contained traces of cyclic and aromatic S-containing compounds afterwards. Lower level of aromatics and the absence of sulphur are some of the factors that contribute to the better fuel stability and environmental properties of the synthetic fuel. GC×GC was further applied for the analysis of products during Jet Fuel Thermal Oxidation Testing (JFTOT), which measures deposit formation of a fuel under simulated engine conditions. JFTOT showed the synthetic fuel to be much more stable than the crude-derived fuel. Copyright © 2011 Elsevier B.V. All rights reserved.

Spicing thing up: Synthetic cannabinoids

PubMed Central

Spaderna, Max; Addy, Peter H; D’Souza, Deepak Cyril

2013-01-01

Rationale Recently, products containing synthetic cannabinoids, collectively referred to as Spice, are increasingly being used recreationally. Objectives The availability, acute subjective effects—including self-reports posted on Erowid—laboratory detection, addictive potential, and regulatory challenges of the Spice phenomenon are reviewed. Results Spice is sold under the guise of potpourri or incense. Unlike THC, the synthetic cannabinoids present in Spice are high-potency, high-efficacy, cannabinoid-receptor full agonists. Since standard urine toxicology does not test for the synthetic cannabinoids in Spice, it is often used by those who want to avoid detection of drug use. These compounds have not yet been subjected to rigorous testing in humans. Acute psychoactive effects include changes in mood, anxiety, perception, thinking, memory, and attention. Adverse effects include anxiety, agitation, panic, dysphoria, psychosis, and bizarre behavior. Psychosis outcomes associated with Spice provide additional data linking cannabinoids and psychosis. Adverse events necessitating intervention by Poison Control Centers, law enforcement, emergency responders, and hospitals are increasing. Despite statutes prohibiting the manufacture, distribution, and sale of Spice products, manufacturers are replacing banned compounds with newer synthetic cannabinoids that are not banned. Conclusions There is an urgent need for better research on the effects of synthetic cannabinoids to help clinicians manage adverse events and to better understand cannabinoid pharmacology in humans. The reported psychosis outcomes associated with synthetic cannabinoids contribute to the ongoing debate on the association between cannabinoids and psychosis. Finally, drug-detection tests for synthetic cannabinoids need to become clinically available. PMID:23836028

Structure elucidation of metabolite x17299 by interpretation of mass spectrometric data.

PubMed

Zhang, Qibo; Ford, Lisa A; Evans, Anne M; Toal, Douglas R

2017-01-01

A major bottleneck in metabolomic studies is metabolite identification from accurate mass spectrometric data. Metabolite x17299 was identified in plasma as an unknown in a metabolomic study using a compound-centric approach where the associated ion features of the compound were used to determine the true molecular mass. The aim of this work is to elucidate the chemical structure of x17299, a new compound by de novo interpretation of mass spectrometric data. An Orbitrap Elite mass spectrometer was used for acquisition of mass spectra up to MS 4 at high resolution. Synthetic standards of N,N,N -trimethyl-l-alanyl-l-proline betaine (l,l-TMAP), a diastereomer, and an enantiomer were chemically prepared. The planar structure of x17299 was successfully proposed by de novo mechanistic interpretation of mass spectrometric data without any laborious purification and nuclear magnetic resonance spectroscopic analysis. The proposed structure was verified by deuterium exchanged mass spectrometric analysis and confirmed by comparison to a synthetic standard. Relative configuration of x17299 was determined by direct chromatographic comparison to a pair of synthetic diastereomers. Absolute configuration was assigned after derivatization of x17299 with a chiral auxiliary group followed by its chromatographic comparison to a pair of synthetic standards. The chemical structure of metabolite x17299 was determined to be l,l-TMAP.

An outbreak of acute delirium from exposure to the synthetic cannabinoid AB-CHMINACA.

PubMed

Tyndall, Joseph A; Gerona, Roy; De Portu, Giuliano; Trecki, Jordan; Elie, Marie-Carmelle; Lucas, Judith; Slish, John; Rand, Kenneth; Bazydlo, Lindsay; Holder, Martina; Ryan, Matthew F; Myers, Paul; Iovine, Nicole; Plourde, Michelle; Weeks, Emily; Hanley, James R; Endres, Greg; St Germaine, Danielle; Dobrowolski, Paul J; Schwartz, Michael

2015-01-01

Synthetic cannabinoid containing products are a public health threat as reflected by a number of outbreaks of serious adverse health effects over the past 4 years. The designer drug epidemic is characterized by the rapid turnover of synthetic cannabinoid compounds on the market which creates a challenge in identifying the particular etiology of an outbreak, confirming exposure in cases, and providing current information to law enforcement. Between 28 May 2014 and 8 June 2014, 35 patients were evaluated and treated at the University of Florida Health Medical Center in Gainesville following reported exposure to a synthetic cannabinoid containing product obtained from a common source. Patients demonstrated acute delirium (24) and seizures (14), and five required ventilator support and ICU-level care; none died. The presence of N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (AB-CHMINACA), or one of its predicted metabolites was confirmed in 15 of 21 cases. A rapid public health response and aggressive public messaging prevented further morbidity, identified the source, and led to law enforcement seizure of the implicated product. The significance of this outbreak lies as much in the rapid occurrence of unpredictable, life-threatening adverse health effects from a newly identified synthetic cannabinoid compound as it does in the multidisciplinary investigation and novel partnership between local public health, the laboratory, and the chemical industry, resulting in termination of the outbreak. A coordinated response and collaboration between law enforcement, the local public health, emergency medical services and Health Center staff, were all key interventions in preventing a more substantial public health outbreak resulting from use of a novel synthetic cannabinoid compound. Real time collaborations between toxicology laboratories, suppliers of analytical standards and the public health system may be useful in the face of future novel chemical exposures.

Synthetic biology era: Improving antibiotic's world.

PubMed

Guzmán-Trampe, Silvia; Ceapa, Corina D; Manzo-Ruiz, Monserrat; Sánchez, Sergio

2017-06-15

The emergence of antibiotic-resistant pathogen microorganisms is problematic in the context of the current spectrum of available medication. The poor specificity and the high toxicity of some available molecules have made imperative the search for new strategies to improve the specificity and to pursue the discovery of novel compounds with increased bioactivity. Using living cells as platforms, synthetic biology has counteracted this problem by offering novel pathways to create synthetic systems with improved and desired functions. Among many other biotechnological approaches, the advances in synthetic biology have made it possible to design and construct novel biological systems in order to look for new drugs with increased bioactivity. Advancements have also been made in the redesigning of RNA and DNA molecules in order to engineer antibiotic clusters for antibiotic overexpression. As for the production of these antibacterial compounds, yeasts and filamentous fungi as well as gene therapy are utilized to enhance protein solubility. Specific delivery is achieved by creating chimeras using plant genes into bacterial hosts. Some of these synthetic systems are currently in clinical trials, proving the proficiency of synthetic biology in terms of both pharmacological activities as well as an increase in the biosafety of treatments. It is possible that we may just be seeing the tip of the iceberg, and synthetic biology applications will overpass expectations beyond our present knowledge. Copyright © 2017. Published by Elsevier Inc.

Synthesis and biological evaluation of febrifugine analogues.

PubMed

Mai, Huong Doan Thi; Thanh, Giang Vo; Tran, Van Hieu; Vu, Van Nam; Vu, Van Loi; Le, Cong Vinh; Nguyen, Thuy Linh; Phi, Thi Dao; Truong, Bich Ngan; Chau, Van Minh; Pham, Van Cuong

2014-12-01

A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.

Synthetic Transformation on Shikimic Acid.

DTIC Science & Technology

1988-03-15

MICROCOP REOUTO TS C -NTOA BUEU fSTNARS193 UtO 1 luff ~ L~ ~% M k, "o, J Synthetic Transformations on0 Shikimic Acid q~t by Ln Edward D. White III DTIC...of a large spectrum of naturally occurring compounds including aromatic amino acids, vitamins, coenzymes, and polyaromatics. 0 HO 5 6 7’ OH HO 3 OH...HO...OH I OMe 1.OHH 0Me 2. +O HO Me OH 8 9 *%* .*p~s - ~ % ’%’a ~ . ~ ~ ~ ~ *a*~h~\\~ .......... ,~ 8 these two compounds resulted in a single product

Simultaneous detection and quantification of select nitromusks, antimicrobial agent, and antihistamine in fish of grocery stores by gas chromatography-mass spectrometry.

PubMed

Foltz, James; Abdul Mottaleb, M; Meziani, Mohammed J; Rafiq Islam, M

2014-07-01

Continually detected biologically persistent nitromusks; galaxolide (HHCB), tonalide (AHTN) and musk ketone (MK), antimicrobial triclosan (TCS), and antihistamine diphenhydramine (DPH) were examined for the first time in edible fillets originating from eight fish species grown in salt- and fresh-water. The sampled fish collected from local grocery stores were homogenized, extracted, pre-concentrated and analyzed by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM). The presence of the target compounds in fish extracts was confirmed based on similar mass spectral features and retention behavior with standards. Internal standard based calibration plots were used for quantification. The HHCB, AHTN, TCS and DPH were consistently observed with concentration of 0.163-0.892, 0.068-0.904, 0.189-1.182, and 0.942-7.472 ng g(-1), respectively. These values are at least 1-3 orders of magnitude lower than those obtained in environmental fish specimens. The MK was not detected in any fish. Copyright © 2013 Elsevier Ltd. All rights reserved.

Semivolatile organic compounds in residential air along the Arizona-Mexico border.

PubMed

Gale, Robert W; Cranor, Walter L; Alvarez, David A; Huckins, James N; Petty, Jimmie D; Robertson, Gary L

2009-05-01

Concerns about indoor air quality and the potential effects on people living in these environments are increasing as more reports about the toxicities and the potential indoor air exposure levels of household-use chemicals and chemicals from housing and fumishing manufacture in air are being assessed. Gas chromatography/mass spectromery was used to confirm numerous airborne contaminants obtained from the analysis of semipermeable membrane devices deployed inside of 52 homes situated along the border between Arizona and Mexico. We also describe nontarget analytes in the organochlorine pesticide fractions of 12 of these homes; this fraction is also the most likely to contain the broadest scope of bioconcentratable chemicals accumulated from the indoor air. Approximately 400 individual components were identified, ranging from pesticides to a wide array of hydrocarbons, fragrances such as the musk xylenes, flavors relating to spices, aldehydes, alcohols, esters and phthalate esters, and other miscellaneous types of chemicals. The results presented in this study demonstrate unequivocally that the mixture of airborne chemicals present indoors is far more complex than previously demonstrated.

Investigations of the Effects of Synthetic Chemicals on the Endocrine System of Common Carp in Lake Mead, Nevada and Arizona

USGS Publications Warehouse

Rosen, Michael R.; Goodbred, Steven L.; Patiño, Reynaldo; Leiker, Thomas A.; Orsak, Erik

2006-01-01

Introduction: Lake Mead is the largest reservoir by volume in the United States and was created by the construction of the 221-meter high Hoover Dam in 1935 at Black Canyon on the lower Colorado River between Nevada and Arizona (fig. 1). Inflows of water into the lake include three rivers, Colorado, Virgin, and Muddy; as well as Las Vegas Wash, which is now perennial because of discharges from municipal wastewater treatment plants (Covay and Leiker, 1998) and urban stormwater runoff. As the population within the Las Vegas Valley began to increase in the 1940s, the treated effluent volume also has increased and in 1993 it constituted about 96 percent of the annual discharge of Las Vegas Wash (Bevans and others, 1996). The mean flow of Las Vegas Wash into Las Vegas Bay from 1992 to 1998 was about 490,000 m3/d (Preissler and others, 1999) and in 2001 increased to 606,000 m3/d (U.S. Bureau of Reclamation, 2001). The nutrient concentration in most areas of the lake is low, but wastewater discharged into Las Vegas Bay has caused an increased level of nutrients and primary productivity (aquatic plant and algal production) in this area of the lake (LaBounty and Horn, 1997). A byproduct of this increase in productivity has been the establishment of an important recreational fishery in Las Vegas Bay. However, concentrations of chlorophyll a (a measure of algal biomass) have also increased (LaBounty and Horn, 1997). In the spring of 2001, parts of Lake Mead experienced massive algal blooms. In addition to nutrient loading by wastewater, the presence of numerous synthetic chemicals in water, bottom sediments, and in fish tissue also has been reported (Bevans and others, 1996). Synthetic chemicals discharging into Las Vegas Bay and Lake Mead (fig. 1) originate from several sources that include surplus residential-irrigation water runoff, stormwater runoff, subsurface inflow, and tertiary treated sewage effluent discharging from three sewage-treatment plants. Chemicals detected in Las Vegas Wash and Bay environments include polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organochlorine pesticides (including DDT and DDE), and 'emerging contaminants' such as fragrances/musks, flame retardants, triclosan and its breakdown products, personal care products, and pharmaceuticals (Bevans and others, 1996; Boyd and Furlong, 2002; Leiker and others, in press). Many of these compounds are able to interact with the endocrine system of animals and potentially cause reproductive impacts. The National Park Service (NPS) manages Lake Mead National Recreation Area (LMNRA) with about 8 million yearly visitors including 500,000 anglers drawn to its world-class recreational fishery. The U.S. Fish and Wildlife Service (FWS) provides management for the federally designated, endangered razorback sucker (Xyrauchen texanus) and for more than 180 species of migratory birds that utilize LMNRA surface waters. These multiple uses of surface water in the area demonstrate their vital importance to the LMNRA as well as the need to maintain the quality of water at levels that are adequate for these uses.

49 CFR 173.223 - Packagings for certain flammable solids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Packagings for certain flammable solids. 173.223 Section 173.223 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS... Class 1 and Class 7 § 173.223 Packagings for certain flammable solids. (a) Packagings for “Musk xylene...

49 CFR 173.223 - Packagings for certain flammable solids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Packagings for certain flammable solids. 173.223 Section 173.223 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS... Class 1 and Class 7 § 173.223 Packagings for certain flammable solids. (a) Packagings for “Musk xylene...

Synthetic organic chemicals in earthworms from agriculture soil amended with municipal biosolids

USDA-ARS?s Scientific Manuscript database

Introduction: Biosolids resulting from municipal wastewater treatment are known to contain residues of pharmaceuticals, personal care products (PPCPs) and other synthetic organic compounds. Many of these are contaminants of emerging concern for their potential endocrine disruption of fish and wildli...

Process for gasification using a synthetic CO.sub.2 acceptor

DOEpatents

Lancet, Michael S.; Curran, George P.

1980-01-01

A gasification process is disclosed using a synthetic CO.sub.2 acceptor consisting essentially of at least one compound selected from the group consisting of calcium oxide and calcium carbonate supported in a refractory carrier matrix, the carrier having the general formula Ca.sub.5 (SiO.sub.4).sub.2 CO.sub.3. A method for producing the synthetic CO.sub.2 acceptor is also disclosed.

Functionalized lipids and surfactants for specific applications.

PubMed

Kepczynski, Mariusz; Róg, Tomasz

2016-10-01

Synthetic lipids and surfactants that do not exist in biological systems have been used for the last few decades in both basic and applied science. The most notable applications for synthetic lipids and surfactants are drug delivery, gene transfection, as reporting molecules, and as support for structural lipid biology. In this review, we describe the potential of the synergistic combination of computational and experimental methodologies to study the behavior of synthetic lipids and surfactants embedded in lipid membranes and liposomes. We focused on select cases in which molecular dynamics simulations were used to complement experimental studies aiming to understand the structure and properties of new compounds at the atomistic level. We also describe cases in which molecular dynamics simulations were used to design new synthetic lipids and surfactants, as well as emerging fields for the application of these compounds. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg. Copyright © 2016 Elsevier B.V. All rights reserved.

[Pharmacological properties of law-evading chemical substances].

PubMed

Funada, Masahiko

2015-09-01

In recent years, frequent cases of people suffering disturbed consciousness, dyspnea, etc. due to abuse of synthetic cannabis and being transported by ambulance or causing traffic accidents are occurring and are becoming a serious social problem in Japan. Most law-evading herbal products have colorful illustrations and logos and are sold as incense or herbs. Law-evading herbal products consist of finely chopped dry vegetative matter mixed with chemical substances (drugs), and the drugs are injurious to health. Analysis of chemical substances in herbal products clarified that they contain synthetic cannabinoid, a chemical component that exhibits action similar to that of hemp. There are many affinity compounds of cannabinoid, so presently, even if a particular drug is regulated, similar compounds that partially differ in structure will propagate. There is thus a cat-and-mouse game between regulations on chemical substances and their propagation. This paper summarizes the pharmacological actions and danger of chemical substances contained in law-evading herbal products by focusing on synthetic cannabinoid or synthetic cathinone, a chemical substance it contains.

Synthetic Origin of Tramadol in the Environment.

PubMed

Kusari, Souvik; Tatsimo, Simplice Joel N; Zühlke, Sebastian; Spiteller, Michael

2016-01-04

The presence of tramadol in roots of Sarcocephalus latifolius trees in Northern Cameroon was recently attributed to point contamination with the synthetic compound. The synthetic origin of tramadol in the environment has now been unambiguously confirmed. Tramadol samples isolated from tramadol pills bought at a street market in downtown Maroua and highly contaminated soil at Houdouvou were analyzed by high-precision (14)C measurements by accelerator mass spectrometry ((14)C AMS): Tramadol from the pills did not contain any radiocarbon, thus indicating that it had been synthesized from (14)C-free petroleum-derived precursors. Crucially, tramadol isolated from the soil was also radiocarbon-free. As all biosynthetic plant compounds must contain radiocarbon levels close to that of the contemporary environment, these results thus confirm that tramadol isolated from the soil cannot be plant-derived. Analyses of S. latifolius seeds, in vitro grown plants, plants from different origins, and stable-isotope labeling experiments further confirmed that synthetic tramadol contaminates the environment. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phytochemicals: Extraction, Isolation, and Identification of Bioactive Compounds from Plant Extracts

PubMed Central

Altemimi, Ammar; Lakhssassi, Naoufal; Baharlouei, Azam; Watson, Dennis G.; Lightfoot, David A.

2017-01-01

There are concerns about using synthetic phenolic antioxidants such as butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) as food additives because of the reported negative effects on human health. Thus, a replacement of these synthetics by antioxidant extractions from various foods has been proposed. More than 8000 different phenolic compounds have been characterized; fruits and vegetables are the prime sources of natural antioxidants. In order to extract, measure, and identify bioactive compounds from a wide variety of fruits and vegetables, researchers use multiple techniques and methods. This review includes a brief description of a wide range of different assays. The antioxidant, antimicrobial, and anticancer properties of phenolic natural products from fruits and vegetables are also discussed. PMID:28937585

Structure-based design, synthesis and biological evaluation of β-glucuronidase inhibitors

NASA Astrophysics Data System (ADS)

Khan, Khalid M.; Ambreen, Nida; Taha, Muhammad; Halim, Sobia A.; Zaheer-ul-Haq; Naureen, Shagufta; Rasheed, Saima; Perveen, Shahnaz; Ali, Sajjad; Choudhary, Mohammad Iqbal

2014-05-01

Using structure-based virtual screening approach, a coumarin derivative ( 1) was identified as β-glucuronidase inhibitor. A focused library of coumarin derivatives was synthesized by eco-benign version of chemical reaction, and all synthetic compounds were characterized by using spectroscopy. These compounds were found to be inhibitor of β-glucuronidase with IC50 values in a micromolar range. All synthetic compounds exhibited interesting inhibitory activity against β-glucuronidase, however, their potency varied substantially from IC50 = 9.9-352.6 µM. Of twenty-one compounds, four exhibited a better inhibitory profile than the initial hit 1. Interestingly, compounds 1e, 1k, 1n and 1p exhibited more potency than the standard inhibitor with IC50 values 34.2, 21.4, 11.7, and 9.9 µM, respectively. We further studied their dose responses and also checked our results by using detergent Triton ×-100. We found that our results are true and not affected by detergent.

Structure-based design, synthesis and biological evaluation of β-glucuronidase inhibitors.

PubMed

Khan, Khalid M; Ambreen, Nida; Taha, Muhammad; Halim, Sobia A; Zaheer-ul-Haq; Naureen, Shagufta; Rasheed, Saima; Perveen, Shahnaz; Ali, Sajjad; Choudhary, Mohammad Iqbal

2014-05-01

Using structure-based virtual screening approach, a coumarin derivative (1) was identified as β-glucuronidase inhibitor. A focused library of coumarin derivatives was synthesized by eco-benign version of chemical reaction, and all synthetic compounds were characterized by using spectroscopy. These compounds were found to be inhibitor of β-glucuronidase with IC50 values in a micromolar range. All synthetic compounds exhibited interesting inhibitory activity against β-glucuronidase, however, their potency varied substantially from IC50 = 9.9-352.6 µM. Of twenty-one compounds, four exhibited a better inhibitory profile than the initial hit 1. Interestingly, compounds 1e, 1k, 1n and 1p exhibited more potency than the standard inhibitor with IC50 values 34.2, 21.4, 11.7, and 9.9 µM, respectively. We further studied their dose responses and also checked our results by using detergent Triton ×-100. We found that our results are true and not affected by detergent.

Emerging role of phenolic compounds as natural food additives in fish and fish products.

PubMed

Maqsood, Sajid; Benjakul, Soottawat; Shahidi, Fereidoon

2013-01-01

Chemical and microbiological deteriorations are principal causes of quality loss of fish and fish products during handling, processing, and storage. Development of rancid odor and unpleasant flavor, changes of color and texture as well as lowering nutritional value in fish can be prevented by appropriate use of additives. Due to the potential health hazards of synthetic additives, natural products, especially antioxidants and antimicrobial agents, have been intensively examined as safe alternatives to synthetic compounds. Polyphenols (PP) are the natural antioxidants prevalent in fruits, vegetables, beverages (tea, wine, juices), plants, seaweeds, and some herbs and show antioxidative and antimicrobial activities in different fish and fish products. The use of phenolic compounds also appears to be a good alternative for sulphiting agent for retarding melanosis in crustaceans. Phenolic compounds have also been successfully employed as the processing aid for texture modification of fish mince and surimi. Thus, plant polyphenolic compounds can serve as potential additives for preventing quality deterioration or to retain the quality of fish and fish products.

Olfactory receptor neuron profiling using sandalwood odorants.

PubMed

Bieri, Stephan; Monastyrskaia, Katherine; Schilling, Boris

2004-07-01

The mammalian olfactory system can discriminate between volatile molecules with subtle differences in their molecular structures. Efforts in synthetic chemistry have delivered a myriad of smelling compounds of different qualities as well as many molecules with very similar olfactive properties. One important class of molecules in the fragrance industry are sandalwood odorants. Sandalwood oil and four synthetic sandalwood molecules were selected to study the activation profile of endogenous olfactory receptors when exposed to compounds from the same odorant family. Dissociated rat olfactory receptor neurons were exposed to the sandalwood molecules and the receptor activation studied by monitoring fluxes in the internal calcium concentration. Olfactory receptor neurons were identified that were specifically stimulated by sandalwood compounds. These neurons expressed olfactory receptors that can discriminate between sandalwood odorants with slight differences in their molecular structures. This is the first study in which an important class of perfume compounds was analyzed for its ability to activate endogenous olfactory receptors in olfactory receptor neurons.

Electrochemical wastewater treatment: influence of the type of carbon and of nitrogen on the organic load removal.

PubMed

Fernandes, Annabel; Coelho, João; Ciríaco, Lurdes; Pacheco, Maria José; Lopes, Ana

2016-12-01

Boron-doped diamond (BDD) and Ti/Pt/PbO 2 anodes were utilized to perform the electrodegradation of synthetic samples containing humic acid in the presence of different organic and inorganic carbon-containing and nitrogen-containing compounds. The influence of the chloride ion in the degradation process of the different synthetic samples was also assessed. The results showed that the anodic oxidation process can efficiently degrade recalcitrant compounds such as humic acid. The presence of carbonate in solution enhances the nitrogen removal, whereas it hinders the oxidation of the organic compounds. When organic nitrogen is present, it is converted to NH 4 + , which in turn is oxidized to nitrate and to volatile nitrogen compounds. Hydroxyl radicals are more prone to oxidize the organic nitrogen than the ammonium nitrogen. The presence of chloride enhances the organic matter and nitrogen removal rates, BDD being the anode material that yields the highest removals.

"Course Thesis" as End of the Laboratory Experimental Program

NASA Astrophysics Data System (ADS)

Dobrev, Alexandre A.

1996-09-01

The "course thesis" is introduced as end of the laboratory experimental program for the students in organic chemistry and consists of two- or three-step synthesis of an organic compound for which good procedures for synthesis are described in the literature. During the second semester, the student searches by himself the parameters and the known synthetical methods for the desired compound beginning with the general chemical encyclopedias and reaching to the original publications. The reaction scheme and the appropriate methods for the preparation of the target compound and its precursors are discussed with a member of the Department as a tutor. All results and information accumulated during the searching and the experimental work are summarized in a small thesis (5-10 pages) written in the style of scientific publication, with a title page, short introduction about the subject, review on the principal synthetic methods, experimental results and the literature sources. The student presents the essence of the thesis at a special Jury in the presence of his collegues and answers questions on the general aspects of the reaction used. The contribution of the thesis is that the student is placed in the real conditions of the research laboratory with self-dependent evaluation of the synthetical methods and all responsability of preparing the target compound.

Formation of low charge state ions of synthetic polymers using quaternary ammonium compounds.

PubMed

Nasioudis, Andreas; Joyce, William F; van Velde, Jan W; Heeren, Ron M A; van den Brink, Oscar F

2010-07-01

Factors such as high polymer dispersity and variation in elemental composition (of copolymers) often complicate the electrospray ionization mass spectrometry (ESI-MS) analysis of synthetic polymers with high molar mass. In the experiments described in this study, quaternary ammonium compounds were observed to facilitate the production of low charge state pseudomolecular ions when added to the spray solution for ESI-MS. This approach was then used for the ESI time-of-flight mass spectrometry (TOF-MS) analysis of synthetic polymers. Hexadecyltrimethylammonium chloride permitted the successful analysis of poly(ethylene glycol) of 2-40 kDa, poly(propylene glycol) and poly(tetramethylene glycol) oligomers. Increasing the quaternary ammonium compounds' concentration results in the production of low charge state pseudomolecular ions. A comparison of structurally different quaternary ammonium compounds showed that the best performance is expected from large molecules with specific charge localization, which leaves the charge available for interactions. The applicability of the method for the MS analysis of other polymeric systems was also studied. In the case of poly(tetramethylene glycol), the method not only shifted the distributions to higher m/z values but also allowed the detection of high molecular weight material that was not observed without addition of the modifier to the spray solution.

Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) of low molecular weight organic compounds and synthetic polymers using zinc oxide (ZnO) nanoparticles.

PubMed

Watanabe, Takehiro; Kawasaki, Hideya; Yonezawa, Tetsu; Arakawa, Ryuichi

2008-08-01

We have developed surface-assisted laser desorption/ionization mass spectrometry using zinc oxide (ZnO) nanoparticles with anisotropic shapes (ZnO-SALDI-MS). The mass spectra showed low background noises in the low m/z, i.e. less than 500 u region. Thus, we succeeded in SALDI ionization on low molecular weight organic compounds, such as verapamil hydrochloride, testosterone, and polypropylene glycol (PPG) (average molecular weight 400) without using a liquid matrix or buffers such as citric acids. In addition, we found that ZnO-SALDI has advantages in post-source decay (PSD) analysis and produced a simple mass spectrum for phospholipids. The ZnO-SALDI spectra for synthetic polymers of polyethylene glycol (PEG), polystyrene (PS) and polymethylmethacrylate (PMMA) showed the sensitivity and molecular weight distribution to be comparable to matrix-assisted laser desorption/ionization (MALDI) spectra with a 2,5-dihydroxybenzoic acid (DHB) matrix. ZnO-SALDI shows good performance for synthetic polymers as well as low molecular weight organic compounds. Copyright (c) 2008 John Wiley & Sons, Ltd.

Synthetic biology strategies toward heterologous phytochemical production.

PubMed

Kotopka, Benjamin J; Li, Yanran; Smolke, Christina D

2018-06-13

Covering: 2006 to 2018Phytochemicals are important sources for the discovery and development of agricultural and pharmaceutical compounds, such as pesticides and medicines. However, these compounds are typically present in low abundance in nature, and the biosynthetic pathways for most phytochemicals are not fully elucidated. Heterologous production of phytochemicals in plant, bacterial, and yeast hosts has been pursued as a potential approach to address sourcing issues associated with many valuable phytochemicals, and more recently has been utilized as a tool to aid in the elucidation of plant biosynthetic pathways. Due to the structural complexity of certain phytochemicals and the associated biosynthetic pathways, reconstitution of plant pathways in heterologous hosts can encounter numerous challenges. Synthetic biology approaches have been developed to address these challenges in areas such as precise control over heterologous gene expression, improving functional expression of heterologous enzymes, and modifying central metabolism to increase the supply of precursor compounds into the pathway. These strategies have been applied to advance plant pathway reconstitution and phytochemical production in a wide variety of heterologous hosts. Here, we review synthetic biology strategies that have been recently applied to advance complex phytochemical production in heterologous hosts.

Antimicrobial activity of synthetic bornyl benzoates against Trypanosoma cruzi

PubMed Central

Corrêa, P R C; Miranda, R R S; Duarte, L P; Silva, G D F; Filho, S A Vieira; Okuma, A A; Carazza, F; Morgado-Díaz, J A; Pinge-Filho, P; Yamauchi, L M; Nakamura, C V; Yamada-Ogatta, S F

2012-01-01

We report here for the first time the in vitro effects of (1S,2R,4S)-1,7,7-trimethyl-bicyclo[2.2.1]heptan-2-yl-3′,4′,5′-trimethoxy benzoate (1) and (1S,2R,4S)-1,7,7-trimethyl-bicyclo[2.2.1]heptan-2-yl benzoate (2) on the growth and ultrastructure of Trypanosoma cruzi. These two synthetic compounds exerted an antiproliferative effect on the epimastigote forms of the parasite. The ICs50/72h of two synthetic L-bornyl benzoates, 1 and 2, was 10.1 and 12.8 μg/ml, respectively. Both compounds were more selective against epimastigotes than HEp-2 cells. Ultrastructural analysis revealed intense cytoplasmic vacuolization and the appearance of cytoplasmic materials surrounded by membranes. The treatment of peritoneal macrophages with compounds 1 and 2 caused a significant decrease in the number of T. cruzi-infected cells. L-Bornyl benzoate derivatives may serve as a potential source for the development of more effective and safer chemotherapeutic agents against T. cruzi infections. PMID:22943546

Exploring the structural diversity in inhibitors of α-synuclein amyloidogenic folding, aggregation and neurotoxicity

NASA Astrophysics Data System (ADS)

Das, Sukanya; Pukala, Tara L.; Smid, Scott D.

2018-05-01

Aggregation of α-Synuclein (αS) protein to amyloid fibrils is a neuropathological hallmark of Parkinson’s disease (PD). Growing evidence suggests that extracellular αS aggregation plays a pivotal role in neurodegeneration found in PD in addition to the intracellular αS aggregates in Lewy bodies (LB). Here, we identified and compared a diverse set of molecules capable of mitigating protein aggregation and exogenous toxicity of αSA53T, a more aggregation-prone αS mutant found in familial PD. For the first time, we investigated the αS anti-amyloid activity of semi-synthetic flavonoid 2', 3', 4' trihydroxyflavone or 2-D08, which was compared with natural flavones myricetin and transilitin, as well as such structurally diverse polyphenols as honokiol and punicalagin. Additionally, two novel synthetic compounds with a dibenzyl imidazolidine scaffold, Compound 1 and Compound 2, were also investigated as they exhibited favourable binding with αSA53T. All seven compounds inhibited αSA53T aggregation as demonstrated by Thioflavin T fluorescence assays, with modified fibril morphology observed by transmission electron microscopy. Ion mobility-mass spectrometry (IM-MS) was used to monitor the structural conversion of native αSA53T into amyloidogenic conformations and all seven compounds preserved the native unfolded conformations of αSA53T following 48 hrs incubation. The presence of each test compound in a 1:2 molar ratio was also shown to inhibit the neurotoxicity of preincubated αSA53T using phaeochromocytoma (PC12) cell viability assays. Among the seven tested compounds 2-D08, honokiol and the synthetic Compound 2 demonstrated the highest inhibition of aggregation, coupled with neuroprotection from preincubated αSA53T in vitro. Molecular docking predicted that all compounds bound near the lysine-rich region of the N-terminus of αSA53T, where the flavonoids and honokiol predominantly interacted with Lys 23. Overall, these findings highlight that i) restricted vicinal trihydroxylation in the flavone B-ring is more effective in stabilizing the native αS conformations, thus blocking amyloidogenic aggregation, than dihydroxylation in both A and B-ring, and ii) honokiol, punicalagin and the synthetic imidazolidine Compound 2 also inhibit αS amyloidogenic aggregation by stabilizing its native conformations. This diverse set of molecules acting on a singular pathological target with predicted binding to αSA53T in the folding-prone N-terminal region may contribute towards novel drug-design for PD.

Exploring the Structural Diversity in Inhibitors of α-Synuclein Amyloidogenic Folding, Aggregation, and Neurotoxicity

PubMed Central

Das, Sukanya; Pukala, Tara L.; Smid, Scott D.

2018-01-01

Aggregation of α-Synuclein (αS) protein to amyloid fibrils is a neuropathological hallmark of Parkinson's disease (PD). Growing evidence suggests that extracellular αS aggregation plays a pivotal role in neurodegeneration found in PD in addition to the intracellular αS aggregates in Lewy bodies (LB). Here, we identified and compared a diverse set of molecules capable of mitigating protein aggregation and exogenous toxicity of αSA53T, a more aggregation-prone αS mutant found in familial PD. For the first time, we investigated the αS anti-amyloid activity of semi-synthetic flavonoid 2′, 3′, 4′ trihydroxyflavone or 2-D08, which was compared with natural flavones myricetin and transilitin, as well as such structurally diverse polyphenols as honokiol and punicalagin. Additionally, two novel synthetic compounds with a dibenzyl imidazolidine scaffold, Compound 1 and Compound 2, were also investigated as they exhibited favorable binding with αSA53T. All seven compounds inhibited αSA53T aggregation as demonstrated by Thioflavin T fluorescence assays, with modified fibril morphology observed by transmission electron microscopy. Ion mobility-mass spectrometry (IM-MS) was used to monitor the structural conversion of native αSA53T into amyloidogenic conformations and all seven compounds preserved the native unfolded conformations of αSA53T following 48 h incubation. The presence of each test compound in a 1:2 molar ratio was also shown to inhibit the neurotoxicity of preincubated αSA53T using phaeochromocytoma (PC12) cell viability assays. Among the seven tested compounds 2-D08, honokiol, and the synthetic Compound 2 demonstrated the highest inhibition of aggregation, coupled with neuroprotection from preincubated αSA53T in vitro. Molecular docking predicted that all compounds bound near the lysine-rich region of the N-terminus of αSA53T, where the flavonoids and honokiol predominantly interacted with Lys 23. Overall, these findings highlight that (i) restricted vicinal trihydroxylation in the flavone B-ring is more effective in stabilizing the native αS conformations, thus blocking amyloidogenic aggregation, than dihydroxylation aggregation in both A and B-ring, and (ii) honokiol, punicalagin, and the synthetic imidazolidine Compound 2 also inhibit αS amyloidogenic aggregation by stabilizing its native conformations. This diverse set of molecules acting on a singular pathological target with predicted binding to αSA53T in the folding-prone N-terminal region may contribute toward novel drug-design for PD. PMID:29888220

[New materia medica project: synthetic biology based bioactive metabolites research in medicinal plant].

PubMed

Wang, Yong

2017-03-25

In the last decade, synthetic biology research has been gradually transited from monocellular parts or devices toward more complex multicellular systems. The emerging plant synthetic biology is regarded as the "next chapter" of synthetic biology. The complex and diverse plant metabolism as the entry point, plant synthetic biology research not only helps us understand how real life is working, but also facilitates us to learn how to design and construct more complex artificial life. Bioactive compounds innovation and large-scale production are expected to be breakthrough with the redesigned plant metabolism as well. In this review, we discuss the research progress in plant synthetic biology and propose the new materia medica project to lift the level of traditional Chinese herbal medicine research.

Transport behaviour of xenobiotic micropollutants in surface waters - an experimental assessment

NASA Astrophysics Data System (ADS)

Schwientek, Marc; Kuch, Bertram; Rügner, Hermann; Dobramysl, Lorenz; Grathwohl, Peter

2013-04-01

Xenobiotics are substances that do not exist in natural systems but are increasingly produced by industrial processes and introduced into the environment. While many of these compounds are eliminated in waste water treatment plants, some are only barely degraded and are discharged into receiving water bodies. Often little is known about their acute or chronic toxicity and even less about their persistence or transport behaviour in aquatic systems. In the present study, the stability and turnover of selected micropollutants along a 7.5 km long segment of the River Ammer in Southwest Germany was investigated (catchment area 134 km²). This stream carries a proportion of treated wastewater which is clearly above the average in German rivers, mainly supplied by a major waste water treatment plant at the upstream end of the studied stream segment. An experimental mass balance approach was chosen where in- and outflow of water and target compounds into and out of the balanced stream segment was measured during base flow conditions. To cover a complete diurnal cycle of wastewater input, pooled samples were collected every 2 h over a sampling period of 24 h. A comparison of bulk mass fluxes showed that carbamazepine, a pharmaceutical, and phosphorous flame retardants, such as TCPP, behave conservative under the given conditions. Some retention was observed for the disinfectant product Triclosan and some polycyclic musk fragrances (e.g., HHCB). TAED, a bleaching activator used in detergents, was completely eliminated along the stream segment. The outcome of the experiment demonstrates the very different persistence of some widely-used micropollutants in aquatic systems. However, the mechanisms involved in their attenuation as well as the fate of the most persistent compounds still remain subject to further research.

Remote distinction of a noxious weed (musk thistle: Carduus nutans) using airborne hyperspectral imagery and the support vector machine classifier

USDA-ARS?s Scientific Manuscript database

Remote detection of invasive plant species using geospatial imagery may significantly improve monitoring, planning, and management practices by eliminating shortfalls such as observer bias and accessibility involved in ground-based surveys. The use of remote sensing for accurate mapping invasion ex...

High Frontier - The Journal for Space and Missile Professionals. Volume 4, Number 3, May 2008

DTIC Science & Technology

2008-05-01

of recovery operations. About SpaceX Founded in 2002 by Elon Musk , Internet entrepreneur and co-creator of PayPal, SpaceX has already developed two...communication loop between the end user, operator, and acquisition commu- nity. It is becoming increasingly important for the squadron to find more

NITRO MUSK ADDUCTS OF RAINBOW TROUT HEMOGLOBIN: DOSE-RESPONSE AND TOXICOKINETICS DETERMINATION BY GC-NICI-MS FOR A SENTINEL SPECIES

EPA Science Inventory

Rainbow trout and other fish species can serve as 'sentinel' species for the assessment of ecological status and the presence of certain environmental contaminants. As such they act as bioindicators of exposure. Here we present seminal data regarding dose-response and toxicokinet...

Myasthenia gravis: subgroup classification and therapeutic strategies.

PubMed

Gilhus, Nils Erik; Verschuuren, Jan J

2015-10-01

Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor, muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. Agrin-associated myasthenia gravis might emerge as a new entity. The prognosis is good with optimum symptomatic, immunosuppressive, and supportive treatment. Pyridostigmine is the preferred symptomatic treatment, and for patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine, and thymectomy are first-line immunosuppressive treatments. Additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies. Long-term drug treatment is essential for most patients and must be tailored to the particular form of myasthenia gravis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Species Delimitation in the Genus Moschus (Ruminantia: Moschidae) and Its High-Plateau Origin.

PubMed

Pan, Tao; Wang, Hui; Hu, Chaochao; Sun, Zhonglou; Zhu, Xiaoxue; Meng, Tao; Meng, Xiuxiang; Zhang, Baowei

2015-01-01

The authenticity of controversial species is a significant challenge for systematic biologists. Moschidae is a small family of musk deer in the Artiodactyla, composing only one genus, Moschus. Historically, the number of species in the Moschidae family has been debated. Presently, most musk deer species were restricted in the Tibetan Plateau and surrounding/adjacent areas, which implied that the evolution of Moschus might have been punctuated by the uplift of the Tibetan Plateau. In this study, we aimed to determine the evolutionary history and delimit the species in Moschus by exploring the complete mitochondrial genome (mtDNA) and other mitochondrial gene. Our study demonstrated that six species, M. leucogaster, M. fuscus, M. moschiferus, M. berezovskii, M. chrysogaster and M. anhuiensis, were authentic species in the genus Moschus. Phylogenetic analysis and molecular dating showed that the ancestor of the present Moschidae originates from Tibetan Plateau which suggested that the evolution of Moschus was prompted by the most intense orogenic movement of the Tibetan Plateau during the Pliocene age, and alternating glacial-interglacial geological eras.

Asymmetric conjugate addition of Grignard reagents to 3-silyl unsaturated esters for the facile preparation of enantioenriched β-silylcarbonyl compounds and allylic silanes.

PubMed

Zhao, Kai; Loh, Teck-Peng

2014-12-08

A highly enantioselective conjugate addition of Grignard reagents to 3-silyl unsaturated esters to deliver synthetically useful chiral β-silylcarbonyl compounds was developed. The synthetic value of this methodology was further illustrated by the synthesis of enantioenriched β-hydroxyl esters and the facile access granted to various α-chiral allylic silanes. A plethora of diastereoselective transformations of β-silylenolates were also investigated and afforded manifold organosilanes that contained contiguous stereogenic centers with excellent enantioselectivity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organic Explosives and Related Compounds. Environmental and Health Considerations

DTIC Science & Technology

1989-03-01

compounds used as explosives and in propellant formulations. While a summiary of synthetic processes is included, emphasis is focused on behavior and...INTRODUCTION .......................................................... 3 SYNTHESIS/ PRODUCTION AND USE .......................................... 5...2 , NG PA DEGDN C(CH2 ON02)4 PETN Figure 1. Structures of Explosives and Related Compounds SYNTHESIS/ PRODUCTION AND USE Methods for the synthesis or

Nature as a source of metabolites with cholinesterase-inhibitory activity: an approach to Alzheimer's disease treatment.

PubMed

Pinho, Brígida R; Ferreres, Federico; Valentão, Patrícia; Andrade, Paula B

2013-12-01

Alzheimer's disease (AD) is the most common cause of dementia, being responsible for high healthcare costs and familial hardships. Despite the efforts of researchers, no treatment able to delay or stop AD progress exists. Currently, the available treatments are only symptomatic, cholinesterase inhibitors being the most widely used drugs. Here we describe several natural compounds with anticholinesterase (acetylcholinesterase and butyrylcholinesterase) activity and also some synthetic compounds whose structures are based on those of natural compounds. Galantamine and rivastigmine are two cholinesterase inhibitors used in therapeutics: galantamine is a natural alkaloid that was extracted for the first time from Galanthus nivalis L., while rivastigmine is a synthetic alkaloid, the structure of which is modelled on that of natural physostigmine. Alkaloids include a high number of compounds with anticholinesterases activity at the submicromolar range. Quinones and stilbenes are less well studied regarding cholinesterase inhibition, although some of them, such as sargaquinoic acid or (+)-α-viniferin, show promising activity. Among flavonoids, flavones and isoflavones are the most potent compounds. Xanthones and monoterpenes are generally weak cholinesterase inhibitors. Nature is an almost endless source of bioactive compounds. Several natural compounds have anticholinesterase activity and others can be used as leader compounds for the synthesis of new drugs. © 2013 Royal Pharmaceutical Society.

40 CFR 60.661 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Distillation Operations § 60.661... for destroying organic compounds and does not extract energy in the form of steam or process heat...

40 CFR 60.661 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Distillation Operations § 60.661... for destroying organic compounds and does not extract energy in the form of steam or process heat...

40 CFR 60.661 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Distillation Operations § 60.661... for destroying organic compounds and does not extract energy in the form of steam or process heat...

Synthesis of monomethyl 5,5'-dehydrodiferulic acid

USDA-ARS?s Scientific Manuscript database

Synthesis of the internal reference compound, monomethyl 5,5’-dehydrodiferulic acid, is described. The synthetic scheme relies on a selective monomethylation of the known compound 5,5-dehydrodivanillin, followed by elaboration into the dehydrodiferulic framework through a dual Horner-Emmons-Wadswort...

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

PubMed Central

2013-01-01

Summary This review which is the second in this series summarises the most common synthetic routes as applied to the preparation of many modern pharmaceutical compounds categorised as containing a six-membered heterocyclic ring. The reported examples are based on the top retailing drug molecules combining synthetic information from both scientific journals and the wider patent literature. It is hoped that this compilation, in combination with the previously published review on five-membered rings, will form a comprehensive foundation and reference source for individuals interested in medicinal, synthetic and preparative chemistry. PMID:24204439

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles.

PubMed

Baumann, Marcus; Baxendale, Ian R

2013-10-30

This review which is the second in this series summarises the most common synthetic routes as applied to the preparation of many modern pharmaceutical compounds categorised as containing a six-membered heterocyclic ring. The reported examples are based on the top retailing drug molecules combining synthetic information from both scientific journals and the wider patent literature. It is hoped that this compilation, in combination with the previously published review on five-membered rings, will form a comprehensive foundation and reference source for individuals interested in medicinal, synthetic and preparative chemistry.

Parts plus pipes: synthetic biology approaches to metabolic engineering

PubMed Central

Boyle, Patrick M.; Silver, Pamela A.

2011-01-01

Synthetic biologists combine modular biological “parts” to create higher-order devices. Metabolic engineers construct biological “pipes” by optimizing the microbial conversion of basic substrates to desired compounds. Many scientists work at the intersection of these two philosophies, employing synthetic devices to enhance metabolic engineering efforts. These integrated approaches promise to do more than simply improve product yields; they can expand the array of products that are tractable to produce biologically. In this review, we explore the application of synthetic biology techniques to next-generation metabolic engineering challenges, as well as the emerging engineering principles for biological design. PMID:22037345

Synthetic fiber production facilities: Background information for proposed standards

NASA Astrophysics Data System (ADS)

Goodwin, D. R.

1982-10-01

Standards of performance to control emissions of volatile organic compounds (VOC) from new, modified, and reconstructed synthetic fiber production facilities are being proposed under section III of the Clean Air Act. This document contains information on the background and authority, regulatory alternatives considered, and environmental and economic impacts of the regulatory alternatives.

77 FR 12508 - Schedules of Controlled Substances: Placement of Five Synthetic Cannabinoids Into Schedule I

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-01

... Final Order, a ``cannabinoid'' is a class of chemical compounds in the marijuana \\3\\ plant that are... constituent of marijuana. ``Synthetic cannabinoids'' are a large family of chemically unrelated structures functionally (biologically) similar to THC, the active principal of marijuana. \\3\\ Note that ``marihuana'' is...

Separation and structural characterization of the new synthetic cannabinoid JWH-018 cyclohexyl methyl derivative "NE-CHMIMO" using flash chromatography, GC-MS, IR and NMR spectroscopy.

PubMed

Angerer, Verena; Bisel, Philippe; Moosmann, Bjoern; Westphal, Folker; Auwärter, Volker

2016-09-01

Synthetic cannabinoids have become an integral part of the drugs of abuse market since many years. The most frequent form of consumption for this class of substances is smoking of herbal mixtures purchased via the Internet. In this article the identification and structure elucidation of a new synthetic cannabinoid, [1-(cyclohexylmethyl)-1H-indol-3-yl](naphthalen-1-yl)methanone, is described. The compound was found along with 5F-ADB in a 'herbal mixture' called 'Jamaican Gold Extreme', which was sent to our laboratory in the context of a suspected intoxication. For isolation of the substance a flash chromatography separation was applied. Structure elucidation was performed using gas chromatography-mass spectrometry (GC-MS), gas chromatography solid-state infrared (GC-sIR) and nuclear magnetic resonance (NMR) analysis. The new compound can be described as the cyclohexyl methyl derivative of the first generation synthetic cannabinoid JWH-018, and the authors suggest to use "NE-CHMIMO" as a semisystematic name. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

AB-CHMINACA, AB-PINACA, and FUBIMINA: Affinity and Potency of Novel Synthetic Cannabinoids in Producing Δ9-Tetrahydrocannabinol–Like Effects in Mice

PubMed Central

Marusich, Julie A.; Lefever, Timothy W.; Antonazzo, Kateland R.; Wallgren, Michael T.; Cortes, Ricardo A.; Patel, Purvi R.; Grabenauer, Megan; Moore, Katherine N.

2015-01-01

Diversion of synthetic cannabinoids for abuse began in the early 2000s. Despite legislation banning compounds currently on the drug market, illicit manufacturers continue to release new compounds for recreational use. This study examined new synthetic cannabinoids, AB-CHMINACA (N-[1-amino-3-methyl-oxobutan-2-yl]-1-[cyclohexylmethyl]-1H-indazole-3-carboxamide), AB-PINACA [N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide], and FUBIMINA [(1-(5-fluoropentyl)-1H-benzo[d]imadazol-2-yl)(naphthalen-1-yl)methanone], with the hypothesis that these compounds, like those before them, would be highly susceptible to abuse. Cannabinoids were examined in vitro for binding and activation of CB1 receptors, and in vivo for pharmacological effects in mice and in Δ9-tetrahydrocannabinol (Δ9-THC) discrimination. AB-CHMINACA, AB-PINACA, and FUBIMINA bound to and activated CB1 and CB2 receptors, and produced locomotor suppression, antinociception, hypothermia, and catalepsy. Furthermore, these compounds, along with JWH-018 [1-pentyl-3-(1-naphthoyl)indole], CP47,497 [rel-5-(1,1-dimethylheptyl)-2-[(1R,3S)-3-hydroxycyclohexyl]-phenol], and WIN55,212-2 ([(3R)-2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone, monomethanesulfonate), substituted for Δ9-THC in Δ9-THC discrimination. Rank order of potency correlated with CB1 receptor-binding affinity, and all three compounds were full agonists in [35S]GTPγS binding, as compared with the partial agonist Δ9-THC. Indeed, AB-CHMINACA and AB-PINACA exhibited higher efficacy than most known full agonists of the CB1 receptor. Preliminary analysis of urinary metabolites of the compounds revealed the expected hydroxylation. AB-PINACA and AB-CHMINACA are of potential interest as research tools due to their unique chemical structures and high CB1 receptor efficacies. Further studies on these chemicals are likely to include research on understanding cannabinoid receptors and other components of the endocannabinoid system that underlie the abuse of synthetic cannabinoids. PMID:26105953

Green Synthetic Alternatives to Organic Compounds and Nanomaterials

EPA Science Inventory

A brief account of reactions involving microwave (MW) exposure of neat reactants or catalyzed by mineral support surfaces, such as alumina, silica, clay, or their ‘doped’ versions, for the rapid one-pot assembly of heterocyclic compounds from in situ generated reactive intermedia...

40 CFR 60.701 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor Processes § 60.701 Definitions. As used in.... Incinerator means an enclosed combustion device that is used for destroying organic compounds. If there is...

40 CFR 60.701 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor Processes § 60.701 Definitions. As used in.... Incinerator means an enclosed combustion device that is used for destroying organic compounds. If there is...

A rapid microtiter plate assay for measuring the effect of compounds on Staphylococcus aureus membrane potential.

PubMed

Gentry, Daniel R; Wilding, Imogen; Johnson, John M; Chen, Dongzhao; Remlinger, Katja; Richards, Cindy; Neill, Susan; Zalacain, Magdalena; Rittenhouse, Stephen F; Gwynn, Michael N

2010-11-01

We developed a homogenous microtiter based assay using the cationic dye 3, 3'-Diethyloxacarbocyanine iodide, DiOC2(3), to measure the effect of compounds on membrane potential in Staphylococcus aureus. In a screen of 372 compounds from a synthetic compound collection with anti-Escherichia coli activity due to unknown modes of action at least 17% demonstrated potent membrane activity, enabling rapid discrimination of nuisance compounds. Copyright © 2010. Published by Elsevier B.V.

Synthetic Cannabinoids-Further Evidence Supporting the Relationship Between Cannabinoids and Psychosis.

PubMed

Fattore, Liana

2016-04-01

Consumption of synthetic mind-altering compounds, also known as "new psychoactive substances," is increasing globally at an alarming rate. Synthetic cannabinoids (SCs) are among the most commonly used new psychoactive substances. They are usually purchased as marijuana-like drugs, marketed as herbal blends and perceived as risk-free by inexperienced users. Yet, contrary to Δ(9)-tetrahydrocannabinol, SCs may lead to severe health consequences, including anxiety, tachycardia, hallucinations, violent behavior, and psychosis. This review focuses on the latest (2010-2015) evidence of psychotic symptoms induced by ingestion of products containing SCs. Reports suggesting that SCs may either exacerbate previously stable psychotic symptoms (in vulnerable individuals) or trigger new-onset psychosis (in individuals with no previous history of psychosis) are reviewed. Pharmacology and toxicology of these compounds are discussed, with particular reference to their psychoactive effects. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Synthesis of new, highly luminescent bis(2,2’-bithiophen-5-yl) substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole

PubMed Central

Kostyuchenko, Anastasia S; L.Yurpalov, Vyacheslav; Kurowska, Aleksandra; Domagala, Wojciech; Pron, Adam

2014-01-01

Summary A new synthetic approach towards the preparation of functionalised, soluble, donor–acceptor (DA) alkylbithiophene derivatives of oxadiazole, thiadiazole and triazole is reported. Taking advantage of the Fiesselmann reaction, reactive bithiophene synthons having alkyl or alkoxy substituents at designated positions are prepared. Following a synthetic strategy, featuring the bottom-up approach, sequential structural elements are built, starting from a simple thiophene compound, until the target molecule is obtained, all in good yield. Supplementing the well established methods of oxadiazole and thiadiazole synthesis, efficient ring closure reaction affording a 4H-1,2,4-triazole unit is presented. All target ambipolar compounds display strong photoluminescence with measured quantum yields up to 0.59. Modification of the demonstrated synthetic routes may be exploited for the preparation of longer, specifically functionalised oligothiophenes, coupled to other heteroaromatic cores. PMID:25161716

Synthesis of new, highly luminescent bis(2,2'-bithiophen-5-yl) substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole.

PubMed

Kostyuchenko, Anastasia S; L Yurpalov, Vyacheslav; Kurowska, Aleksandra; Domagala, Wojciech; Pron, Adam; Fisyuk, Alexander S

2014-01-01

A new synthetic approach towards the preparation of functionalised, soluble, donor-acceptor (DA) alkylbithiophene derivatives of oxadiazole, thiadiazole and triazole is reported. Taking advantage of the Fiesselmann reaction, reactive bithiophene synthons having alkyl or alkoxy substituents at designated positions are prepared. Following a synthetic strategy, featuring the bottom-up approach, sequential structural elements are built, starting from a simple thiophene compound, until the target molecule is obtained, all in good yield. Supplementing the well established methods of oxadiazole and thiadiazole synthesis, efficient ring closure reaction affording a 4H-1,2,4-triazole unit is presented. All target ambipolar compounds display strong photoluminescence with measured quantum yields up to 0.59. Modification of the demonstrated synthetic routes may be exploited for the preparation of longer, specifically functionalised oligothiophenes, coupled to other heteroaromatic cores.

Toward antituberculosis drugs: in silico screening of synthetic compounds against Mycobacterium tuberculosisl,d-transpeptidase 2.

PubMed

Billones, Junie B; Carrillo, Maria Constancia O; Organo, Voltaire G; Macalino, Stephani Joy Y; Sy, Jamie Bernadette A; Emnacen, Inno A; Clavio, Nina Abigail B; Concepcion, Gisela P

2016-01-01

Mycobacterium tuberculosis (Mtb) the main causative agent of tuberculosis, is the main reason why this disease continues to be a global public health threat. It is therefore imperative to find a novel antitubercular drug target that is unique to the structural machinery or is essential to the growth and survival of the bacterium. One such target is the enzyme l,d-transpeptidase 2, also known as LdtMt2, a protein primarily responsible for the catalysis of 3→3 cross-linkages that make up the mycolyl-arabinogalactan-peptidoglycan complex of Mtb. In this study, structure-based pharmacophore screening, molecular docking, and in silico toxicity evaluations were employed in screening compounds from a database of synthetic compounds. Out of the 4.5 million database compounds, 18 structures were identified as high-scoring, high-binding hits with very satisfactory absorption, distribution, metabolism, excretion, and toxicity properties. Two out of the 18 compounds were further subjected to in vitro bioactivity assays, with one exhibiting a good inhibitory activity against the Mtb H37Ra strain.

Synthesis of three bromophenols from red algae as PTP1B inhibitors

NASA Astrophysics Data System (ADS)

Guo, Shuju; Li, Jing; Li, Ting; Shi, Dayong; Han, Lijun

2011-01-01

Bromophenols are a set of natural products widely distributed in seaweed, most of which exhibit interesting and useful biological activities. To develop a reliable and efficient synthetic route to these natural bromophenols, three of them, 3,4-dibromo-5-(2'-bromo-3',4'-dihydroxy-6'-methoxymethyl-benzyl)-benzene-1,2-diol (compound 9), 3,4-dibromo-5-(2'-bromo-6'-ethoxy methyl-3',4'-dihydroxybenzyl)-benzene-1,2-diol (compound 10), and 3-bromo-4-(3'-bromo-4',5'-dihydroxy benzyl)-5-(ethoxymethyl)-benzene-1,2-diol (compound 14), isolated from red marine algae, have been synthesized in eight steps with an overall yield of 14.4%, 14.4%, and 18.2% respectively, via a practical approach employing bromination, Wolff-Kishner-Huang reduction and a Friedel-Crafts reaction as key steps. The protein tyrosine phosphatase 1B (PTP1B) inhibitory activities of the synthetic compounds were evaluated by the colorimetric assay. The results show that these compounds are moderate PTP1B inhibitors. The synthesis of these bromophenol derivatives makes in vivo studies of their structure-activity relationships and inhibition activity against PTP1B possible.

Experimental Realisation of Elusive Multiple-bonded Aluminium Compounds: A New Horizon in the Aluminium Chemistry.

PubMed

Inoue, Shigeyoshi; Bag, Prasenjit; Weetman, Catherine

2018-05-23

Synthesis and isolation of stable main group compounds featuring multiple bonds has been of keen interest for the last several decades. Multiply bonded complexes were obtained using sterically demanding substituents that provide kinetic and thermodynamic stability. Many of these compounds have unusual structural and electronic properties that challenges the classical concept of covalent multiple bonding. In contrast, analogous aluminium compounds are scarce in spite of its high natural abundance. The parent dialumene (Al2H2) has been calculated to be extremely weak, thus making Al multiple bonds a challenging synthetic target. This review provides an overview of these recent advances in the cutting edge synthetic approaches used to obtain aluminium homo- and heterodiatomic multiply bonded complexes. Additionally, the reactivity of these novel compounds towards various small molecules and reagents will be discussed herein. This review provides an overview on the current progress in aluminium multiple bond chemistry and the careful ligand design required to stabilise these reactive species. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and mechanistic studies of curcumin analog-based oximes as potential anticancer agents.

PubMed

Qin, Hua-Li; Leng, Jing; Youssif, Bahaa G M; Amjad, Muhammad Wahab; Raja, Maria Abdul Ghafoor; Hussain, Muhammad Ajaz; Hussain, Zahid; Kazmi, Syeda Naveed; Bukhari, Syed Nasir Abbas

2017-09-01

The incidence of cancer can be decreased by chemoprevention using either natural or synthetic agents. Apart from synthetic compounds, numerous natural products have exhibited promising potential to inhibit carcinogenesis in vivo. In this study, α, β-unsaturated carbonyl-based anticancer compounds were used as starting materials to synthesize new oxime analogs. The findings from the antiproliferative assay using seven different human cancer cell lines provided a clear picture of structure-activity relationship. The oxime analogs namely 7a and 8a showed strong antiproliferative activity against the cell lines. The mechanistic effects of compounds on EGFR-TK kinases and tubulin polymerization and BRAF V 600E were investigated. In addition, the efficacy of compounds in reversing the efflux-mediated resistance developed by cancer cells was also studied. The compounds 5a and 6a displayed potent activity on various targets such as BRAF V 600E and EGFR-TK kinases and also exhibited strong antiproliferative activity against different cell lines hence showing potential of multifunctional anticancer agents. © 2017 John Wiley & Sons A/S.

Effect of natural and semi-synthetic cadinanes from Heterotheca inuloides on NF-κB, Nrf2 and STAT3 signaling pathways and evaluation of their in vitro cytotoxicity in human cancer cell lines.

PubMed

Egas, Verónica; Millán, Estrella; Collado, Juan A; Ramírez-Apan, Teresa; Méndez-Cuesta, Carlos A; Muñoz, Eduardo; Delgado, Guillermo

2017-06-15

The effects of ten natural cadinane sesquiterpenoids isolated from Heterotheca inuloides on the pathways of the NF-κB, Nrf2 and STAT3 transcription factors were studied for the first time. The main constituent in this species, 7-hydroxy-3,4-dihydrocadalene (1), showed anti-NF-κB activity and activated the antioxidant Nrf2 pathway, which may explain the properties reported for the traditional use of the plant. In addition to the main metabolite, a structurally similar compound, 7-hydroxy-cadalene (2), also displayed anti-NF-κB activity. Thus, both natural compounds were used as templates for the preparation of a novel semi-synthetic derivative set, including esters and carbamates, which were evaluated for their potential in vitro antiproliferative activities against six human cancer cell lines. Carbamate derivatives 32 and 33 were found to exhibit potent activity against human colorectal adenocarcinoma and showed important selectivity in cancer cells. Among ester derivatives, compound 13 was determined to be a more potent NF-κB inhibitor and Nrf2 activator than its parent, 7-hydroxy-3,4-dihydrocadalene (1). Furthermore, this compound decreases levels of phospho-IκBα, a protein complex involved in the NF-κB activation pathway. Molecular simulations suggest that all active compounds interact with the activation loop of the IKKβ subunit in the IKK complex, which is the responsible of IκBα phosphorylation. Thus, we identified two natural, and one semi-synthetic, NF-κB and Nrf2 modulators and two new promising cytotoxic compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Positive modulator of bone morphogenic protein-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Positive modulator of bone morphogenic protein-2

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

2009-01-27

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

SensiPath: computer-aided design of sensing-enabling metabolic pathways.

PubMed

Delépine, Baudoin; Libis, Vincent; Carbonell, Pablo; Faulon, Jean-Loup

2016-07-08

Genetically-encoded biosensors offer a wide range of opportunities to develop advanced synthetic biology applications. Circuits with the ability of detecting and quantifying intracellular amounts of a compound of interest are central to whole-cell biosensors design for medical and environmental applications, and they also constitute essential parts for the selection and regulation of high-producer strains in metabolic engineering. However, the number of compounds that can be detected through natural mechanisms, like allosteric transcription factors, is limited; expanding the set of detectable compounds is therefore highly desirable. Here, we present the SensiPath web server, accessible at http://sensipath.micalis.fr SensiPath implements a strategy to enlarge the set of detectable compounds by screening for multi-step enzymatic transformations converting non-detectable compounds into detectable ones. The SensiPath approach is based on the encoding of reactions through signature descriptors to explore sensing-enabling metabolic pathways, which are putative biochemical transformations of the target compound leading to known effectors of transcription factors. In that way, SensiPath enlarges the design space by broadening the potential use of biosensors in synthetic biology applications. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

On irreversible adsorption of electron-donating compounds in aqueous solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamon, Hajime; Atsushi, Masanori; Okazaki, Morio

Activated carbons and synthetic adsorbents have been used for liquid purification and wastewater treatment. The feasibility of an adsorption process depends greatly on the cost of regeneration of spent adsorbents. If irreversible adsorption occurs, regeneration of spent adsorbent is very difficult. Hence, it is very important to understand why irreversible adsorption appears in aqueous solution. In the adsorption of electron-donating compounds such as phenol, aniline, L-phenylalanine, and L-tyrosine from aqueous solution, irreversibility was observed on activated carbon and graphite. The compounds, except L-tyrosine, were reversibly adsorbed on a synthetic adsorbent. In the case where the carbonaceous adsorbents contacted the aqueousmore » solution containing electron-donating compounds for a long time, the irreversible amount adsorbed increased with the contact time. A two-state adsorption model was used to explain why the irreversible adsorption of electron-donating compound appears in aqueous solution. First, the compound is adsorbed in the precursor state for irreversible adsorption, and then moves into its irreversible state over a potential energy barrier after a long contact time. The appearance of irreversible adsorption was qualitatively explained by the two-state adsorption model.« less

A study of various synthetic routes to produce a halogen-labeled traction fluid

NASA Technical Reports Server (NTRS)

Jones, W. R., Jr.; Zimmer, H.

1978-01-01

Several synthetic routes were studied for the synthesis of the compound 1, 1, 3-trimethyl-1, 3-dicyclohexyl-2 chloropropane. This halogen-labeled fluid would be of use in the study of high traction lubricants under elastohydrodynamic lubrication conditions using infrared emission spectroscopy. The synthetic routes included: dimerization of alpha-methylstyrene, methanol addition to alpha-methylstyrene, a Wittig reaction, and an organometallic approach. Because of steric hindrance and competing reactions, none of these routes were successful.

Establishing Chlamydomonas reinhardtii as an industrial biotechnology host

PubMed Central

Scaife, Mark A; Nguyen, Ginnie TDT; Rico, Juan; Lambert, Devinn; Helliwell, Katherine E; Smith, Alison G

2015-01-01

Microalgae constitute a diverse group of eukaryotic unicellular organisms that are of interest for pure and applied research. Owing to their natural synthesis of value-added natural products microalgae are emerging as a source of sustainable chemical compounds, proteins and metabolites, including but not limited to those that could replace compounds currently made from fossil fuels. For the model microalga, Chlamydomonas reinhardtii, this has prompted a period of rapid development so that this organism is poised for exploitation as an industrial biotechnology platform. The question now is how best to achieve this? Highly advanced industrial biotechnology systems using bacteria and yeasts were established in a classical metabolic engineering manner over several decades. However, the advent of advanced molecular tools and the rise of synthetic biology provide an opportunity to expedite the development of C. reinhardtii as an industrial biotechnology platform, avoiding the process of incremental improvement. In this review we describe the current status of genetic manipulation of C. reinhardtii for metabolic engineering. We then introduce several concepts that underpin synthetic biology, and show how generic parts are identified and used in a standard manner to achieve predictable outputs. Based on this we suggest that the development of C. reinhardtii as an industrial biotechnology platform can be achieved more efficiently through adoption of a synthetic biology approach. Significance Statement Chlamydomonas reinhardtii offers potential as a host for the production of high value compounds for industrial biotechnology. Synthetic biology provides a mechanism to generate generic, well characterised tools for application in the rational genetic manipulation of organisms: if synthetic biology principles were adopted for manipulation of C. reinhardtii, development of this microalga as an industrial biotechnology platform would be expedited. PMID:25641561

Bacterial degradation of synthetic and kraft lignin by axenic and mixed culture and their metabolic products.

PubMed

Chandra, Ram; Bharagava, Ram Naresh

2013-11-01

Pulp paper mill effluent has high pollution load due to presence of lignin and its derivatives as major colouring and polluting constituents. In this study, two lignin degrading bacteria IITRL1 and IITRSU7 were isolated and identified as Citrobacter freundii (FJ581026) and Citrobacter sp. (FJ581023), respectively. In degradation study by axenic and mixed culture, mixed bacterial culture was found more effective compared to axenic culture as it decolourized 85 and 62% of synthetic and kraft lignin whereas in axenic conditions, bacterium IITRL1 and IITRSU7 decolourized 61 and 64% synthetic and 49 and 54% kraft lignin, respectively. Further, the mixed bacterial culture also showed the removal of 71, 58% TOC; 78, 53% AOX; 70, 58% COD and 74, 58% lignin from synthetic and kraft lignin, respectively. The ligninolytic enzyme was characterized as manganese peroxidase by SDS-PAGE yielding a single band of 43 KDa. The HPLC analysis of degraded samples showed reduction as well as shifting of peaks compared to control indicating the degradation as well as transformation of compounds. Further, in GC-MS analysis of synthetic and kraft lignin degraded samples, hexadecanoic acid was found as recalcitrant compounds while 2,4,6-trichloro-phenol, 2,3,4,5-tetrachloro-phenol and pentachloro-phenol were detected as new metabolites.

36 CFR 242.25 - Subsistence taking of fish, wildlife, and shellfish: general regulations.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., mountain goat, moose, musk ox, Dall sheep, wolf, and wolverine. Bow means a longbow, recurve bow, or... (land) otter, red squirrel, flying squirrel, ground squirrel, marmot, wolf, or wolverine. Fyke net means...) Utilization of fish, wildlife, or shellfish. (1) You may not use wildlife as food for a dog or furbearer, or...

36 CFR 242.25 - Subsistence taking of fish, wildlife, and shellfish: general regulations.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., mountain goat, moose, musk ox, Dall sheep, wolf, and wolverine. Bow means a longbow, recurve bow, or... (land) otter, red squirrel, flying squirrel, ground squirrel, marmot, wolf, or wolverine. Fyke net means...) Utilization of fish, wildlife, or shellfish. (1) You may not use wildlife as food for a dog or furbearer, or...

36 CFR 242.25 - Subsistence taking of fish, wildlife, and shellfish: general regulations.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., mountain goat, moose, musk ox, Dall sheep, wolf, and wolverine. Bow means a longbow, recurve bow, or... (land) otter, red squirrel, flying squirrel, ground squirrel, marmot, wolf, or wolverine. Fyke net means...) Utilization of fish, wildlife, or shellfish. (1) You may not use wildlife as food for a dog or furbearer, or...

[Prevalence of new designer drugs and their legal status in Japan].

PubMed

Kikura-Hanajiri, Ruri; Uchiyama, Nahoko; Kawamura, Maiko; Ogata, Jun; Goda, Yukihiro

2013-01-01

In recent years, many analogs of narcotics have been widely distributed as easily available psychotropic substances and have become a serious problem in Japan. To counter the spread of these non-controlled substances, the Pharmaceutical Affairs Law in Japan was amended in 2006 to establish a new category; Designated Substances in order to more strictly control these substances. In April 2007, 31 compounds and 1 plant were first controlled as Designated Substances. Before 2007, the major compounds distributed in the Japanese illegal drug market were tryptamines, phenethylamines and piperazines. Alkyl nitrites, such as isobutyl nitrite and isopentyl nitrite, were also widely distributed. After they were listed as Narcotics or Designated Substances in 2007, these compounds, especially the tryptamines, quickly disappeared from the market. In their place, cathinone derivatives have been widely distributed, as well as different phenethylamines and piperazines. Additionally, in recent years, new herbal products containing synthetic cannabinoids have appeared globally. As at July 2012, 78 substances (including 1 plant; Salvia divinorum) were listed in the category of Designated Substances. They were 13 tryptamines, 17 phenethylamines, 11 cathinones, 4 piperazines, 23 synthetic cannabinoids, 6 alkyl nitrites, 3 other compounds and 1 plant. In this review, we show our survey of the spread of new designer drugs in Japan, focusing especially on synthetic cannabinoids and cathinone derivatives. Also, the prevalence and legal status of these substances in other countries will be presented.

Plastic waste to liquid oil through catalytic pyrolysis using natural and synthetic zeolite catalysts.

PubMed

Miandad, R; Barakat, M A; Rehan, M; Aburiazaiza, A S; Ismail, I M I; Nizami, A S

2017-11-01

This study aims to examine the catalytic pyrolysis of various plastic wastes in the presence of natural and synthetic zeolite catalysts. A small pilot scale reactor was commissioned to carry out the catalytic pyrolysis of polystyrene (PS), polypropylene (PP), polyethylene (PE) and their mixtures in different ratios at 450°C and 75min. PS plastic waste resulted in the highest liquid oil yield of 54% using natural zeolite and 50% using synthetic zeolite catalysts. Mixing of PS with other plastic wastes lowered the liquid oil yield whereas all mixtures of PP and PE resulted in higher liquid oil yield than the individual plastic feedstocks using both catalysts. The GC-MS analysis revealed that the pyrolysis liquid oils from all samples mainly consisted of aromatic hydrocarbons with a few aliphatic hydrocarbon compounds. The types and amounts of different compounds present in liquid oils vary with some common compounds such as styrene, ethylbenzene, benzene, azulene, naphthalene, and toluene. The FT-IR data also confirmed that liquid oil contained mostly aromatic compounds with some alkanes, alkenes and small amounts of phenol group. The produced liquid oils have high heating values (HHV) of 40.2-45MJ/kg, which are similar to conventional diesel. The liquid oil has potential to be used as an alternative source of energy or fuel production. Copyright © 2017 Elsevier Ltd. All rights reserved.

Encapsulation of natural ingredient for skin protection via nanoemulsion process

NASA Astrophysics Data System (ADS)

Asmatulu, Eylem; Usta, Aybala; Alzahrani, Naif; Patil, Vinay; Vanderwall, Adeesha

2017-04-01

Many of the sunscreens are used during the hot summer time to protect the skin surface. However, some of ingredients in the sunscreens, such as oxybenzone, retinyl palmitate and synthetic fragrances including parabens, phthalates and synthetic musk may disrupt the cells on the skin and create harmful effects to human body. Natural oils may be considered for substitution of harmful ingredients in sunscreens. Many natural oils (e.g., macadamia oil, sesame oil, almond oil and olive oil) have UV protective property and on top of that they have natural essences. Among the natural oils, olive oil has a long history of being used as a home remedy for skincare. Olive oil is used or substituted for cleanser, moisturizer, antibacterial agent and massage reliever for muscle fatigue. It is known that sun protection factor (SPF) of olive oil is around eight. There has been relatively little scientific work performed on the effect of olive oil on the skin as sunscreen. With nanoencapsulation technique, UV light protection of the olive oil can be extended which will provide better coverage for the skin throughout the day. In the present study, natural olive oil was incorporated with DI water and surfactant (sodium dodecyl sulfate - SDS) and sonicated using probe sonicators. Sonication time, and concentrations of olive oil, DI water and surfactant were investigated in detail. The produced nanoemulsions were characterized using dynamic light scattering, and UV-Vis spectroscopy. It is believed that the nanoencupsulation of olive oil could provide better skin protection by slow releasing and deeper penetration of the nanoemulsion on skin surface. Undergraduate engineering students were involved in the project and observed all the process during the laboratory studies, as well as data collection, analysis and presentation. This experience based learning will likely enhance the students' skills and interest in the scientific and engineering studies.

Green Synthetic Alternatives to Organic Compounds and Nanomaterials-May 2008

EPA Science Inventory

A brief account of reactions involving microwave (MW) exposure of neat reactants or catalyzed by mineral support surfaces, such as alumina, silica, clay, or their ‘doped’ versions, for the rapid one-pot assembly of heterocyclic compounds from in situ generated reactive intermedia...

40 CFR 60.665 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI... level or reading indicated by the organics monitoring device at the outlet of the absorber, condenser... the final recovery device in a recovery system, and where an organic compound monitoring device is not...

40 CFR 60.665 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI... level or reading indicated by the organics monitoring device at the outlet of the absorber, condenser... the final recovery device in a recovery system, and where an organic compound monitoring device is not...

Larvicidal activity and structure activity relationship of cinnamoyl amides from Zanthoxylum armatum and their synthetic analogues against diamondback moth, Plutella xylostella.

PubMed

Kumar, Vishal; Reddy, S G Eswara; Bhardwaj, Anuja; Dolma, Shudh Kirti; Kumar, Neeraj

2016-01-01

Cinnamoyl amides isolated from Zanthoxylum armatum (Rutaceae) and their synthetic analogues were tested for their insecticidal activity against the second instar larvae of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Yponomeutidae) to determine the promising structures with insecticidal activity. Most of the test compounds showed promising activity against larvae of P. xylostella. However, the activities of different compounds varied depending on the presence of different substituents at various positions of both the aromatic rings A and B. Among the tested compounds, 8, N-(3-bromo-4-methoxyphenethyl)cinnamamide showed best larvicidal activity with an LC50 = 62.13 mg/L followed by 6, N-(3׳-bromophenethyl)cinnamamide (LC50=128.49 mg/L) and 2 N-(4׳-methoxyphenylethyl)cinnamamide (LC50 = 225.65 mg/L).

Larvicidal activity and structure activity relationship of cinnamoyl amides from Zanthoxylum armatum and their synthetic analogues against diamondback moth, Plutella xylostella

PubMed Central

Kumar, Vishal; Reddy, S. G. Eswara; Bhardwaj, Anuja; Dolma, Shudh Kirti; Kumar, Neeraj

2016-01-01

Cinnamoyl amides isolated from Zanthoxylum armatum (Rutaceae) and their synthetic analogues were tested for their insecticidal activity against the second instar larvae of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Yponomeutidae) to determine the promising structures with insecticidal activity. Most of the test compounds showed promising activity against larvae of P. xylostella. However, the activities of different compounds varied depending on the presence of different substituents at various positions of both the aromatic rings A and B. Among the tested compounds, 8, N-(3-bromo-4-methoxyphenethyl)cinnamamide showed best larvicidal activity with an LC50 = 62.13 mg/L followed by 6, N-(3׳-bromophenethyl)cinnamamide (LC50=128.49 mg/L) and 2 N-(4׳-methoxyphenylethyl)cinnamamide (LC50 = 225.65 mg/L). PMID:27231477

Transition metal catalyzed manipulation of non-polar carbon–hydrogen bonds for synthetic purpose

PubMed Central

MURAI, Shinji

2011-01-01

The direct addition of ortho C–H bonds in various aromatic compounds such as ketones, esters, imines, imidates, nitriles, and aldehydes to olefins and acetylenes can be achieved with the aid of transition metal catalysts. The ruthenium catalyzed reaction is usually highly efficient and useful as a general synthetic method. The coordination to the metal center by a heteroatom in a directing group such as carbonyl and imino groups in aromatic compounds is the key step in this process. Mechanistically, the reductive elimination to form a C–C bond is the rate-determining step, while the C–H bond cleavage step is not. PMID:21558759

New synthetic possibilities for the preparation of liquid crystalline dicyclohexyl derivatives

NASA Astrophysics Data System (ADS)

Sasnouski, Genadz; Bezborodov, Vladimir; Dabrowski, Roman S.; Dziaduszek, Jerzy

2000-05-01

A new synthetic approach for the preparation of two- and three ring liquid crystalline compounds possessing trans,trans-dicyclohexyl moiety is proposed and realized. Recently discovered reaction of Grignard reagents with esters leading to 1-substituted cyclopropanoles in the presence of tetraisopropoxytitanium was used as a key stage. Starting from ethyl trans-4-alkylcyclohexancarboxylates the corresponding 6-(4-alkylcyclohexyl)-3-alkyl (or aryl) cyclohex-2-en-1-ones have been prepared. Their catalytic hydrogenation in the base media gave mainly saturated trans, trans-ketones which are liquid crystalline and have been used also as a promising intermediate products for the preparation of different kinds of other LC compounds.

The chemistry of cationic polyphosphorus cages – syntheses, structure and reactivity

PubMed Central

Holthausen, Michael H.

2014-01-01

The aim of this review is to provide a comprehensive view of the chemistry of cationic polyphosphorus cages. The synthetic protocols established for their preparation, which are all based on the functionalization of P4, and their intriguing follow-up chemistry are highlighted. In addition, this review intends to foster the interest of the inorganic, organic, catalytic and material oriented chemical communities in the versatile field of polyphosphorus cage compounds. In the long term, this is envisioned to contribute to the development of new synthetic procedures for the functionalization of P4 and its transformation into (organo-)phosphorus compounds and materials of added value. PMID:24740160

Eco-friendly synthesis, physicochemical studies, biological assay and molecular docking of steroidal oxime-ethers

PubMed Central

Alam, Mahboob; Lee, Dong-Ung

2015-01-01

The aim of this study was to report the synthesis of biologically active compounds; 7-(2′-aminoethoxyimino)-cholest-5-ene (4), a steroidal oxime-ether and its derivatives (5, 6) via a facile microwave assisted solvent free reaction methodology. This new synthetic, eco-friendly, sustainable protocol resulted in a remarkable improvement in the synthetic efficiency (85-93 % yield) and high purity using basic alumina. The synthesized compounds were screened for their antibacterial against six bacterial strains by disc diffusion method and antioxidant potential by DPPH assay. The binding capabilities of a compound 6 exhibiting good antibacterial potential were assessed on the basis of molecular docking studies and four types of three-dimensional molecular field descriptors. Moreover the structure-antimicrobial activity relationships were studied using some physicochemical and quantum-chemical parameters with GAMESS interface as well as WebMO Job Manager by using the basic level of theory. Hence, this synthetic approach is believed to provide a better scope for the synthesis of steroidal oxime-ether analogues and will be a more practical alternative to the presently existing procedures. Moreover, detailed in silico docking studies suggested the plausible mechanism of steroidal oxime-ethers as effective antimicrobial agents. PMID:27330525

A Prospective Randomized, Double-Blind, Two-Period Crossover Pharmacokinetic Trial Comparing Green Coffee Bean Extract-A Botanically Sourced Caffeine-With a Synthetic USP Control.

PubMed

Morton, Kayce; Knight, Katelin; Kalman, Douglas; Hewlings, Susan

2018-04-16

Coffee is a primary dietary source of the chlorogenic acids (CGAs) of phenolic compounds. Coffee contains caffeine and other phytonutrients, including CGAs. Caffeine on its own has been well characterized and descried pharmacokinetically in the literature, less so for CGAs. The purpose of this double-blind crossover study was to determine the comparative pharmacokinetics of CGAs with caffeine (natural extract) with synthetic caffeine (US Pharmacopeia [USP] standard). Sixteen healthy male subjects were randomly assigned to take 1 dose of product 1, 60 mg of botanically sourced caffeine from 480 mg of green coffee bean extract, or product 2, 60 mg of synthetic USP caffeine, with 5 days between. Blood analysis was done to determine the levels of CGA compounds, more specifically 3-, 4-, and 5-caffeoylquinic acid (CQA), and serum caffeine. The natural caffeine extract exhibited mean peak concentrations (C max ) of 3-CQA (11.4 ng/mL), 4-CQA (6.84 ng/mL), and 5-CQA (7.20 ng/mL). The mean systemic 4-hour exposure (AUC 0-4 h ) was 3-CQA (27.3 ng·h/mL), 4-CQA (16.1 ng·h/mL), and 5-CQA (15.7 ng·h/mL). The median t max was 3-CQA (1.00 hour), 4-CQA (1.00 hour), and 5-CQA (1.50 hours). The t max of caffeine was 0.75 hours (natural extract) and 0.63 hours (synthetic caffeine). C max and AUC 0-4 h of serum caffeine were statistically equivalent between products. The geometric least-squares mean ratios (GMRs) of C max and AUC 0-4 h of caffeine were 97.77% (natural extract) and 98.33% (synthetic caffeine). It would appear that CGA compounds from the natural caffeine extract are bioavailable, and 3-CGA may be the compound most absorbed. In addition, caffeine sourced from natural extract versus synthetic were statistically similar for pharmacokinetic parameters. There were no adverse events or safety concerns. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Fungal Anticancer Metabolites: Synthesis Towards Drug Discovery.

PubMed

Barbero, Margherita; Artuso, Emma; Prandi, Cristina

2018-01-01

Fungi are a well-known and valuable source of compounds of therapeutic relevance, in particular of novel anticancer compounds. Although seldom obtainable through isolation from the natural source, the total organic synthesis still remains one of the most efficient alternatives to resupply them. Furthermore, natural product total synthesis is a valuable tool not only for discovery of new complex biologically active compounds but also for the development of innovative methodologies in enantioselective organic synthesis. We undertook an in-depth literature searching by using chemical bibliographic databases (SciFinder, Reaxys) in order to have a comprehensive insight into the wide research field. The literature has been then screened, refining the obtained results by subject terms focused on both biological activity and innovative synthetic procedures. The literature on fungal metabolites has been recently reviewed and these publications have been used as a base from which we consider the synthetic feasibility of the most promising compounds, in terms of anticancer properties and drug development. In this paper, compounds are classified according to their chemical structure. This review summarizes the anticancer potential of fungal metabolites, highlighting the role of total synthesis outlining the feasibility of innovative synthetic procedures that facilitate the development of fungal metabolites into drugs that may become a real future perspective. To our knowledge, this review is the first effort to deal with the total synthesis of these active fungi metabolites and demonstrates that total chemical synthesis is a fruitful means of yielding fungal derivatives as aided by recent technological and innovative advancements. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Use of a combined effect model approach for discriminating between ABCB1- and ABCC1-type efflux activities in native bivalve gill tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faria, Melissa; CESAM & Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro; Pavlichenko, Vasiliy

Aquatic organisms, such as bivalves, employ ATP binding cassette (ABC) transporters for efflux of potentially toxic chemicals. Anthropogenic water contaminants can, as chemosensitizers, disrupt efflux transporter function enabling other, putatively toxic compounds to enter the organism. Applying rapid amplification of cDNA ends (RACE) PCR we identified complete cDNAs encoding ABCB1- and ABCC1-type transporter homologs from zebra mussel providing the molecular basis for expression of both transporter types in zebra mussel gills. Further, efflux activities of both transporter types in gills were indicated with dye accumulation assays where efflux of the dye calcein-am was sensitive to both ABCB1- (reversin 205, verapamil)more » and ABCC1- (MK571) type specific inhibitors. The assumption that different inhibitors targeted different efflux pump types was confirmed when comparing measured effects of binary inhibitor compound mixtures in dye accumulation assays with predictions from mixture effect models. Effects by the MK571/reversin 205 mixture corresponded better with independent action, whereas reversin 205/verapamil joint effects were better predicted by the concentration addition model indicating different and equal targets, respectively. The binary mixture approach was further applied to identify the efflux pump type targeted by environmentally relevant chemosensitizing compounds. Pentachlorophenol and musk ketone, which were selected after a pre-screen of twelve compounds that previously had been identified as chemosensitizers, showed mixture effects that corresponded better with concentration addition when combined with reversine 205 but with independent action predictions when combined with MK571 indicating targeting of an ABCB1-type efflux pump by these compounds. - Highlights: • Sequences and function of ABC efflux transporters in bivalve gills were explored. • Full length Dreissena polymorpha abcb1 and abcc1 cDNA sequences were identified. • A mixture effect design with inhibitors was applied in transporter activity assays. • ABCB1- and ABCC-type efflux activities were distinguished in native gill tissue. • Inhibitory action of environmental chemicals targeted ABCB1-type efflux activity.« less

Synthetic Fabrication of Nanoscale MoS2-Based Transition Metal Sulfides

PubMed Central

Wang, Shutao; An, Changhua; Yuan, Jikang

2010-01-01

Transition metal sulfides are scientifically and technologically important materials. This review summarizes recent progress on the synthetic fabrication of transition metal sulfides nanocrystals with controlled shape, size, and surface functionality. Special attention is paid to the case of MoS2 nanoparticles, where organic (surfactant, polymer), inorganic (support, promoter, doping) compounds and intercalation chemistry are applied.

Sub-lethal activity of small molecules from natural sources and their synthetic derivatives against biofilm forming nosocomial pathogens.

PubMed

Villa, Federica; Villa, Stefania; Gelain, Arianna; Cappitelli, Francesca

2013-01-01

Nowadays, the patient safety is seriously jeopardized by the emergence and spread of nosocomial pathogens in the form of biofilm that is resistant to traditional and affordable antimicrobials. Although advances in organic synthesis have extended the lifetime of classic antibiotics through synthetic modifications, the search of innovative antibiofilm compounds from natural sources can provide new templates, novel targets and unique mechanisms that should have advantages over known antimicrobial agents. Testing sub-lethal concentrations of crude extracts and/or isolated compounds from plants and microorganisms is critical to acting on mechanisms subtler than the killing activity, e.g. those influencing the multicellular behavior, offering an elegant way to develop novel antimicrobial-free antibiofilm strategies. Herein we discussed the search and biological activity of small molecules from natural sources and their synthetic derivatives able to modulate biofilm genesis of nosocomial pathogens through non-microbicidal mechanisms (sub-lethal concentrations). The present work offers an overview about the approaches applied to the discovery of lead small molecules including a) conventional drug design methods like screening of chemical compounds obtained from nature and b) computer- aided drug design approaches. Finally, a classification (not exhaustive but representative) based on the natural origin of small molecules and their synthetic derivatives was reported. The information presented in this review should be of interest to a broad range of disciplines and represents an effort to summarize experimental research and advances in this field.

Design, Synthesis and Testing of Metabolically-Stable Antimalarial Compounds

DTIC Science & Technology

2008-05-01

resistant to chloroquine . Developed during World War II, this once was the drug of choice to battle malaria across the globe. Physicians have been forced...compound obtained from the Chinese licorice root, was shown to have antimalarial properties. Synthetic analogues have subsequently been produced and

40 CFR 60.704 - Test methods and procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor Processes § 60... compound j in ppm, as measured for organics by Method 18 and measured for hydrogen and carbon monoxide by...

40 CFR 60.705 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor...) (i), (ii) or (iii), the concentration level or reading indicated by the organics monitoring device at... recovery system, and where an organic compound monitoring device is not used: (i) All 3-hour periods of...

40 CFR 60.705 - Reporting and recordkeeping requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor...) (i), (ii) or (iii), the concentration level or reading indicated by the organics monitoring device at... recovery system, and where an organic compound monitoring device is not used: (i) All 3-hour periods of...

40 CFR 60.704 - Test methods and procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor Processes § 60... basis of compound j in ppm, as measured for organics by Method 18 and measured for hydrogen and carbon...

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

PubMed Central

Bassanini, Ivan; Hult, Karl

2015-01-01

Summary Dicarboxylic acids and their derivatives (esters and anhydrides) have been used as acylating agents in lipase-catalyzed reactions in organic solvents. The synthetic outcomes have been dimeric or hybrid derivatives of bioactive natural compounds as well as functionalized polyesters. PMID:26664578

Theranostics Targeting Metastatic Breast Cancer

DTIC Science & Technology

The emphasis of this first year of the award, as planned, has been on synthetic chemistry to obtain materials to test in histology, PET (positron...the previous, highly cytotoxic, compound maytensin A. We have also prepared an agent intended solely for PET , i.e. compound 4; this takes advantage of

Characteristics of a newly isolated fungus Geotrichum candidum Dec 1 with broad degradation spectrum of xenobiotic compounds.

PubMed

Shoda, M

2003-01-01

A newly isolated fungus, Geotrichum candidum Dec 1 (abbreviated as Dec 1), was found to have the ability to degrade many xenobiotic compounds such as synthetic dyes, food coloring agents, molasses, organic halogens, lignin and kraft pulp effluents. The broad spectrum of the degradation of these compounds are associated mainly with peroxidases produced by the fungus.

Removal of PPCPs from the sludge supernatant in a one stage nitritation/anammox process.

PubMed

Alvarino, T; Suarez, S; Katsou, E; Vazquez-Padin, J; Lema, J M; Omil, F

2015-01-01

Pharmaceutical and personal care products (PPCPs) are extensively used and can therefore find their way into surface, groundwater and municipal and industrial effluents. In this work, the occurrence, fate and removal mechanisms of 19 selected PPCPs was investigated in an 'ELiminación Autótrofa de Nitrógeno' (ELAN) reactor of 200 L. In this configuration, ammonium oxidation to nitrite and the anoxic ammonium oxidation (anammox)processes occur simultaneously in a single-stage reactor under oxygen limited conditions. The ELAN process achieved high removal (>80%) of the studied hormones, naproxen, ibuprofen, bisphenol A and celestolide, while it was not effective in the removal of carbamazepine (<7%), diazepam (<7%) and fluoxetine (<30%). Biodegradation was the dominant removal mechanism, while sorption was only observed for musk fragrances, fluoxetine and triclosan. The sorption was strongly dependent on the granule size, with smaller granules facilitating the sorption of the target compounds. Increased hydraulic retention time enhanced the intramolecular diffusion of the PPCPs into the granules, and thus increased the solid phase concentration. The increase of nitritation rate favored the removal of ibuprofen, bisphenol A and triclosan, while the removal of erythromycin was strongly correlated to the anammox reaction rate.

Highly sweet compounds of plant origin.

PubMed

Kim, Nam-Cheol; Kinghorn, A Douglas

2002-12-01

The demand for new alternative "low calorie" sweeteners for dietetic and diabetic purposes has increased worldwide. Although the currently developed and commercially used highly sweet sucrose substitutes are mostly synthetic compounds, the search for such compounds from natural sources is continuing. As of mid-2002, over 100 plant-derived sweet compounds of 20 major structural types had been reported, and were isolated from more than 25 different families of green plants. Several of these highly sweet natural products are marketed as sweeteners or flavoring agents in some countries as pure compounds, compound mixtures, or refined extracts. These highly sweet natural substances are reviewed herein.

Multifactorial antimicrobial wood protectants

Treesearch

Robert D. Coleman; Carol A. Clausen

2008-01-01

It is unlikely that a single antimicrobial compound, whether synthetic or natural, will provide the ‘magic bullet’ for eliminating multiple biological agents affecting wood products. Development of synergistic combinations of selected compounds, especially those derived from natural sources, is recognized as a promising approach to improved wood protection. Recent...

40 CFR 52.1783 - Original identification of plan section.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Residual Oil Burners 15 NCAC 2D.0902, Applicability (Volatile Organic Compounds) 15 NCAC 2H.0603... or Residual Oil Burners 15 NCAC 2D.0939, Determination of Volatile Organic Compound Emissions (B) The... 2D.0943, Synthetic Organic Chemical and Polymer Manufacturing 15 NCAC 2D.0944, Manufacturing of...

50 CFR 100.25 - Subsistence taking of fish, wildlife, and shellfish: general regulations.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., Sitka black-tailed deer, elk, mountain goat, moose, musk ox, Dall sheep, wolf, and wolverine. Bow means..., wolf, or wolverine. Fyke net means a fixed, funneling (fyke) device used to entrap fish. Gear means any... wildlife as food for a dog or furbearer, or as bait, except as allowed for in § __.26, § __.27, or § __.28...

36 CFR 242.25 - Subsistence taking of fish, wildlife, and shellfish: general regulations.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., mountain goat, moose, musk ox, Dall sheep, wolf, and wolverine. Bow means a longbow, recurve bow, or..., ground squirrel, marmot, wolf, or wolverine. Fyke net means a fixed, funneling (fyke) device used to... may not use wildlife as food for a dog or furbearer, or as bait, except as allowed for in § 242.26...

36 CFR 242.25 - Subsistence taking of fish, wildlife, and shellfish: general regulations.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., mountain goat, moose, musk ox, Dall sheep, wolf, and wolverine. Bow means a longbow, recurve bow, or..., ground squirrel, marmot, wolf, or wolverine. Fyke net means a fixed, funneling (fyke) device used to... may not use wildlife as food for a dog or furbearer, or as bait, except as allowed for in § 242.26...

50 CFR 100.25 - Subsistence taking of fish, wildlife, and shellfish: general regulations.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., Sitka black-tailed deer, elk, mountain goat, moose, musk ox, Dall sheep, wolf, and wolverine. Bow means..., wolf, or wolverine. Fyke net means a fixed, funneling (fyke) device used to entrap fish. Gear means any... wildlife as food for a dog or furbearer, or as bait, except as allowed for in § __.26, § __.27, or § __.28...

50 CFR 100.25 - Subsistence taking of fish, wildlife, and shellfish: general regulations.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., Sitka black-tailed deer, elk, mountain goat, moose, musk ox, Dall sheep, wolf, and wolverine. Bow means..., wolf, or wolverine. Fyke net means a fixed, funneling (fyke) device used to entrap fish. Gear means any... wildlife as food for a dog or furbearer, or as bait, except as allowed for in § __.26, § __.27, or § __.28...

China Report, Red Flag, Number 1, 1 January 1985

DTIC Science & Technology

1985-03-05

li0dSOf,the thlrd’ f°Urth’ and the fifth e^ elon . It is impossible for them to change. In recent times I have always told foreign guests that the...people sell hides, musk , and other articles to Han people in exchange for cloth and salt. The Yi costumes are completely different from the Han

Natural Marine and Synthetic Xenobiotics Get on Nematode's Nerves: Neuro-Stimulating and Neurotoxic Findings in Caenorhabditis elegans.

PubMed

Lieke, Thora; Steinberg, Christian E W; Ju, Jingjuan; Saul, Nadine

2015-05-06

Marine algae release a plethora of organic halogenated compounds, many of them with unknown ecological impact if environmentally realistic concentrations are applied. One major compound is dibromoacetic acid (DBAA) which was tested for neurotoxicity in the invertebrate model organism Caenorhabditis elegans (C. elegans). This natural compound was compared with the widespread synthetic xenobiotic tetrabromobisphenol-A (TBBP-A) found in marine sediments and mussels. We found a neuro-stimulating effect for DBAA; this is contradictory to existing toxicological reports of mammals that applied comparatively high dosages. For TBBP-A, we found a hormetic concentration-effect relationship. As chemicals rarely occur isolated in the environment, a combination of both organobromines was also examined. Surprisingly, the presence of DBAA increased the toxicity of TBBP-A. Our results demonstrated that organohalogens have the potential to affect single organisms especially by altering the neurological processes, even with promoting effects on exposed organisms.

Chiral Alkyl Halides: Underexplored Motifs in Medicine

PubMed Central

Gál, Bálint; Bucher, Cyril; Burns, Noah Z.

2016-01-01

While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and medicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biological systems. A number of chlorinated compounds in the pharmaceutical and food industries, as well as a growing number of halogenated marine natural products showing unique bioactivity, illustrate the role that chiral alkyl halides can play in drug discovery. Through a series of case studies, we demonstrate in this review that these motifs can indeed be stable under physiological conditions, and that halogenation can enhance bioactivity through both steric and electronic effects. Our hope is that, by placing such compounds in the minds of the chemical community, they may gain more traction in drug discovery and inspire more synthetic chemists to develop methods for selective halogenation. PMID:27827902

Diversity-oriented synthesis yields novel multistage antimalarial inhibitors.

PubMed

Kato, Nobutaka; Comer, Eamon; Sakata-Kato, Tomoyo; Sharma, Arvind; Sharma, Manmohan; Maetani, Micah; Bastien, Jessica; Brancucci, Nicolas M; Bittker, Joshua A; Corey, Victoria; Clarke, David; Derbyshire, Emily R; Dornan, Gillian L; Duffy, Sandra; Eckley, Sean; Itoe, Maurice A; Koolen, Karin M J; Lewis, Timothy A; Lui, Ping S; Lukens, Amanda K; Lund, Emily; March, Sandra; Meibalan, Elamaran; Meier, Bennett C; McPhail, Jacob A; Mitasev, Branko; Moss, Eli L; Sayes, Morgane; Van Gessel, Yvonne; Wawer, Mathias J; Yoshinaga, Takashi; Zeeman, Anne-Marie; Avery, Vicky M; Bhatia, Sangeeta N; Burke, John E; Catteruccia, Flaminia; Clardy, Jon C; Clemons, Paul A; Dechering, Koen J; Duvall, Jeremy R; Foley, Michael A; Gusovsky, Fabian; Kocken, Clemens H M; Marti, Matthias; Morningstar, Marshall L; Munoz, Benito; Neafsey, Daniel E; Sharma, Amit; Winzeler, Elizabeth A; Wirth, Dyann F; Scherer, Christina A; Schreiber, Stuart L

2016-10-20

Antimalarial drugs have thus far been chiefly derived from two sources-natural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products and are underrepresented in typical screening collections. We report the identification of such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase. These molecules are curative in mice at a single, low dose and show activity against all parasite life stages in multiple in vivo efficacy models. Our findings identify bicyclic azetidines with the potential to both cure and prevent transmission of the disease as well as protect at-risk populations with a single oral dose, highlighting the strength of diversity-oriented synthesis in revealing promising therapeutic targets.

An Expanding World of Novel Psychoactive Substances: Opioids

PubMed Central

Zawilska, Jolanta B.

2017-01-01

The abuse of novel psychoactive substances (NPS) has been increasing dramatically worldwide since late 2000s. By the end of 2015, more than 560 NPS had been reported to the European Monitoring Centre for Drugs and Drug Addiction. Although the most popular compounds are synthetic cannabinoids and psychostimulatory derivatives of cathinone (so-called β-keto-amphetamines), novel synthetic opioids have recently emerged on the recreational drug market. They include fentanyl (a potent narcotic analgesic) and its analogs (e.g., acetylfentanyl, acryloylfentanyl, carfentanil, α-methylfentanyl, 3-methylfentanyl, furanylfentanyl, 4-fluorobutyrylfentanyl, 4-methoxybutyrylfentanyl, 4-chloroisobutyrylfentanyl, 4-fluoroisobutyrylfentanyl, tetrahydrofuranylfentanyl, cyclopentylfentanyl, and ocfentanil) and compounds with different chemical structures, such as AH-7921, MT-45, and U-47700. This survey provides an overview of the pharmacological properties, pattern of use, and desired and unwanted effects of the above-listed novel opioids. Special emphasis is given to cases of non-fatal and lethal intoxication involving these compounds. PMID:28713291

Natural Marine and Synthetic Xenobiotics Get on Nematode’s Nerves: Neuro-Stimulating and Neurotoxic Findings in Caenorhabditis elegans

PubMed Central

Lieke, Thora; Steinberg, Christian E. W.; Ju, Jingjuan; Saul, Nadine

2015-01-01

Marine algae release a plethora of organic halogenated compounds, many of them with unknown ecological impact if environmentally realistic concentrations are applied. One major compound is dibromoacetic acid (DBAA) which was tested for neurotoxicity in the invertebrate model organism Caenorhabditis elegans (C. elegans). This natural compound was compared with the widespread synthetic xenobiotic tetrabromobisphenol-A (TBBP-A) found in marine sediments and mussels. We found a neuro-stimulating effect for DBAA; this is contradictory to existing toxicological reports of mammals that applied comparatively high dosages. For TBBP-A, we found a hormetic concentration-effect relationship. As chemicals rarely occur isolated in the environment, a combination of both organobromines was also examined. Surprisingly, the presence of DBAA increased the toxicity of TBBP-A. Our results demonstrated that organohalogens have the potential to affect single organisms especially by altering the neurological processes, even with promoting effects on exposed organisms. PMID:25955755

Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?

PubMed Central

2015-01-01

High-throughput biology has contributed a wealth of data on chemicals, including natural products (NPs). Recently, attention was drawn to certain, predominantly synthetic, compounds that are responsible for disproportionate percentages of hits but are false actives. Spurious bioassay interference led to their designation as pan-assay interference compounds (PAINS). NPs lack comparable scrutiny, which this study aims to rectify. Systematic mining of 80+ years of the phytochemistry and biology literature, using the NAPRALERT database, revealed that only 39 compounds represent the NPs most reported by occurrence, activity, and distinct activity. Over 50% are not explained by phenomena known for synthetic libraries, and all had manifold ascribed bioactivities, designating them as invalid metabolic panaceas (IMPs). Cumulative distributions of ∼200,000 NPs uncovered that NP research follows power-law characteristics typical for behavioral phenomena. Projection into occurrence–bioactivity–effort space produces the hyperbolic black hole of NPs, where IMPs populate the high-effort base. PMID:26505758

Synthetic organic compounds and their transformation products in groundwater: occurrence, fate and mitigation.

PubMed

Postigo, Cristina; Barceló, Damià

2015-01-15

Groundwater constitutes the main source of public drinking water supply in many regions. Thus, the contamination of groundwater resources by organic chemicals is a matter of growing concern because of its potential effects on public health. The present manuscript compiles the most recent works related to the study of synthetic organic compounds (SOCs) in groundwater, with special focus on the occurrence of contaminants not or barely covered by previously published reviews, e.g., pesticide and pharmaceutical transformation products, lifestyle products, and industrial chemicals such as corrosion inhibitors, brominated and organophosphate flame retardants, plasticizers, volatile organic compounds (VOCs), and polycyclic aromatic hydrocarbons (PAHs). Moreover, the main challenges in managed aquifer recharge, i.e., reclaimed water injection and infiltration, and riverbank filtration, regarding natural attenuation of organic micropollutants are discussed, and insights into the future chemical quality of groundwater are provided. Copyright © 2014 Elsevier B.V. All rights reserved.

Cinnamoyl compounds as simple molecules that inhibit p300 histone acetyltransferase.

PubMed

Costi, Roberta; Di Santo, Roberto; Artico, Marino; Miele, Gaetano; Valentini, Paola; Novellino, Ettore; Cereseto, Anna

2007-04-19

Cinnamoly compounds 1a-c and 2a-d were designed, synthesized, and in vitro tested as p300 inhibitors. At different degrees, all tested compounds were proven to inactivate p300, particularly, derivative 2c was the most active inhibitor, also showing high specificity for p300 as compared to other histone acetyltransferases. Most notably, 2c showed anti-acetylase activity in mammalian cells. These compounds represent a new class of synthetic inhibitors of p300, characterized by simple chemical structures.

Assessing synthetic strategies: total syntheses of (+/-)-neodolabellane-type diterpenoids.

PubMed

Valente, Cory; Organ, Michael G

2008-01-01

Two strategies, namely a cross-metathesis/ring-closing metathesis and Pd-catalyzed Stille allylation/Nozaki-Hiyama-Kishi coupling, are examined for the preparation of neodolabellane-type diterpenoids 1 and 2. Whereas the first approach possessed synthetic limitations, the latter was successfully employed to provide compounds 1 and 2 in 8.8% (14 steps) and 8% (15 steps) overall yields, respectively.

Synthetic process for preparation of high surface area electroactive compounds for battery applications

DOEpatents

Evenson, Carl; Mackay, Richard

2013-07-23

A process is disclosed for the preparation of electroactive cathode compounds useful in lithium-ion batteries, comprising exothermic mixing of low-cost precursors and calcination under appropriate conditions. The exothermic step may be a spontaneous flameless combustion reaction. The disclosed process can be used to prepare any lithium metal phosphate or lithium mixed metal phosphate as a high surface area single phase compound.

Contribution of synthetic and naturally occurring organobromine compounds to bromine mass in marine organisms.

PubMed

Wan, Yi; Jones, Paul D; Wiseman, Steve; Chang, Hong; Chorney, Dave; Kannan, Kurunthachalam; Zhang, Kun; Hu, Jian-Ying; Khim, Jong Seong; Tanabe, Shinsuke; Lam, Michael H W; Giesy, John P

2010-08-15

An extraction, separation, and purification method was developed for the identification and quantification of total bromine (TBr), extractable organobromine (EOBr), and five classes of identified EOBrs. Instrumental neutron activation analysis (INAA) was utilized to quantify EOBr and TBr. The method was then applied to liver samples of tuna, albatross, and polar bear collected from remote marine locations. Polybrominated biphenyls (PBBs), polybrominated diphenyl ethers (PBDEs), bromophenols (BRPs), hydroxylated (OH-) and methoxylated (MeO-) PBDEs were analyzed as identified EOBr. The majority of the bromine in these marine organisms was nonextractable or inorganic, with EOBr accounting for 10-28% of the TBr. Of the identified EOBr, in tuna and albatross, naturally occurring compounds, including MeO-PBDEs, OH-PBDEs, and BPRs, were prevalent. However, the identifiable EOBr in polar bears consisted primarily of synthetic compounds, including PBDEs and PBBs. Overall, 0.08-0.11% and 0.008-0.012% of EOBr and TBr, respectively, were identified. The proportion of EOBr that was identified in marine organisms was relatively small compared to the proportions for organofluorine and organochlorine compounds. This could be related to the great diversity of naturally occurring organobromine compounds in the environment. Naturally occurring brominated fatty acids were estimated to be the predominant compounds in the EOBr fraction.

Does bedding affect the airway and allergy?

PubMed

Siebers, R W; Crane, J

2011-04-01

Various cross-sectional and longitudinal studies have suggested that synthetic bedding is associated with asthma, allergic rhinitis and eczema while feather bedding seems to be protective. Synthetic bedding items have higher house dust mite allergen levels than feather bedding items. This is possibly the mechanism involved although fungal and bacterial proinflammatory compounds and volatile organic compounds may play a role. In this review we present and discuss the epidemiological evidence and suggest possible mechanisms. Primary intervention studies are required to show whether feather bedding is protective for the development of childhood asthma and allergic diseases while secondary intervention studies are required to potentially reduce symptoms and medication use in subjects with established disease.

Synthesis of branched iminosugars through a hypervalent iodine(III)-mediated radical-polar crossover reaction.

PubMed

Santana, Andrés G; Paz, Nieves R; Francisco, Cosme G; Suárez, Ernesto; González, Concepción C

2013-08-02

The synthesis of a novel type of branched iminosugars is described. This synthetic strategy is based on two key reactions: first, an aldol reaction with formaldehyde in order to introduce selectively the hydroxymethyl branch, and second, a tandem β-fragmentation-intramolecular cyclization reaction. The combination of both reactions afforded a battery of compounds exhibiting a great structural complexity, with the concomitant formation of a quaternary center, starting from readily available aldoses. With this approach we have demonstrated the usefulness of the fragmentation of anomeric alkoxyl radicals (ARF) promoted by the PhIO/I2 system for the preparation of new compounds with potential interest for both medicinal and synthetic chemists.

Locomotor activity and discriminative stimulus effects of a novel series of synthetic cathinone analogs in mice and rats.

PubMed

Gatch, Michael B; Dolan, Sean B; Forster, Michael J

2017-04-01

Recent years have seen an increase in the recreational use of novel, synthetic psychoactive substances. There are little or no data on the abuse liability of many of the newer compounds. The current study investigated the discriminative stimulus and locomotor effects of a series of synthetic analogs of cathinone: α-pyrrolidinopropiophenone (α-PPP), α-pyrrolidinohexiophenone (α-PHP), α-pyrrolidinopentiothiophenone (α-PVT), 3,4-methylenedioxybutiophenone (MDPBP), and ethylone. Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine or methamphetamine from vehicle. Each of the compounds produced an inverted-U dose-effect on locomotor activity. Maximal effects were similar among the test compounds, but potencies varied with relative potencies of MDPBP > α-PPP = α-PHP > ethylone > α-PVT. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine. α-PPP, α-PHP, and ethylone fully substituted for cocaine. α-PVT produced a maximum of 50% cocaine-appropriate responding, and MDPBP produced an inverted-U-shaped dose-effect curve with maximum effects of 67%. These data provide initial evidence that these structurally similar, emerging novel psychoactive substances demonstrate potential for abuse and may be utilized for their stimulant-like effects, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of the classical psychostimulants cocaine and/or methamphetamine.

Environmental Chemicals Modulate Polar Bear (Ursus maritimus) Peroxisome Proliferator-Activated Receptor Gamma (PPARG) and Adipogenesis in Vitro.

PubMed

Routti, Heli; Lille-Langøy, Roger; Berg, Mari K; Fink, Trine; Harju, Mikael; Kristiansen, Kurt; Rostkowski, Pawel; Rusten, Marte; Sylte, Ingebrigt; Øygarden, Lene; Goksøyr, Anders

2016-10-04

We studied interactions between polar bear peroxisome proliferator-activated receptor gamma (pbPPARG) and selected compounds using a luciferase reporter assay and predictions through molecular docking. Furthermore, we studied adipogenesis by liver and adipose tissue extracts from a polar bear and three synthetic mixtures of contaminants in murine 3T3-L1 preadipocytes and polar bear adipose tissue-derived stem cells (pbASCs). PCB153 and p,p'-DDE antagonized pbPPARG, although their predicted receptor-ligand affinity was weak. PBDEs, tetrabromobisphenol A, and PCB170 had a weak agonistic effect on pbPPARG, while hexabromocyclododecane, bisphenol A, oxychlordane, and endosulfan were weak antagonists. pbPPARG-mediated luciferase activity was suppressed by synthetic contaminant mixtures reflecting levels measured in polar bear adipose tissue, as were transcript levels of PPARG and the PPARG target gene fatty acid binding protein 4 (FABP4) in pbASCs. Contaminant extracts from polar bear tissues enhanced triglyceride accumulation in murine 3T3-L1 cells and pbASCs, whereas triglyceride accumulation was not affected by the synthetic mixtures. Chemical characterization of extracts using nontarget methods revealed presence of exogenous compounds that have previously been reported to induce adipogenesis. These compounds included phthalates, tonalide, and nonylphenol. In conclusion, major legacy contaminants in polar bear adipose tissue exert antagonistic effects on PPARG, but adipogenesis by a mixture containing emerging compounds may be enhanced through PPARG or other pathways.

An Overview of New Possible Treatments of Alzheimer's Disease, Based on Natural Products and Semi-Synthetic Compounds.

PubMed

Zanforlin, Enrico; Zagotto, Giuseppe; Ribaudo, Giovanni

2017-11-17

Dementias and all related neurodegenerative diseases of the Central Nervous System (CNS) are a current issue arousing a great deal of interest in the international scientific community. This is due to the increasing number of patients suffering from these diseases. These pathologies represent a serious problem, not only concerning the quality of life of the patient, but in addition, the enormous economic efforts that society has to do for their treatment. There are currently a few strategies that are available in order to prevent the progression or to mitigate symptoms of the aforementioned diseases. This consideration is particularly true if we consider the specific pathology of Alzheimer's Disease (AD). We performed a literature search for peer-reviewed articles using different databases, such as PubMed or Scopus, and exploiting different keywords and different logical operators. Ninety-eight papers were included in the review. Four papers give an overview of the background of the dementias all over the world. The remaining papers are focused on new possibilities of treatment with natural and semi-synthetic compounds for AD. The aim of this review is to give an overview of new and promising natural products and semi-synthetic compounds which could represent a source of "lead compounds" for the development of new potential drugs that could be a valid therapeutic strategy for the treatment of this pathology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Identification of AB-FUBINACA metabolites in authentic urine samples suitable as urinary markers of drug intake using liquid chromatography quadrupole tandem time of flight mass spectrometry.

PubMed

Vikingsson, Svante; Gréen, Henrik; Brinkhagen, Linda; Mukhtar, Shahzabe; Josefsson, Martin

2016-09-01

Synthetic cannabinoids are a group of psychoactive drugs presently widespread among drug users in Europe. Analytical methods to measure these compounds in urine are in demand as urine is a preferred matrix for drug testing. For most synthetic cannabinoids, the parent compounds are rarely detected in urine. Therefore urinary metabolites are needed as markers of drug intake. AB-FUBINACA was one of the top three synthetic cannabinoids most frequently found in seizures and toxicological drug screening in Sweden (2013-2014). Drug abuse is also reported from several other countries such as the USA and Japan. In this study, 28 authentic case samples were used to identify urinary markers of AB-FUBINACA intake using liquid chromatography quadrupole tandem time of flight mass spectrometry and human liver microsomes. Three metabolites suitable as markers of drug intake were identified and at least two of them were detected in all but one case. In total, 15 urinary metabolites of AB-FUBINACA were reported, including hydrolxylations on the indazole ring and the amino-oxobutane moiety, dealkylations and hydrolysis of the primary amide. No modifications on the fluorobenzyl side-chain were observed. The parent compound was detected in 54% of the case samples. Also, after three hours of incubation with human liver microsomes, 77% of the signal from the parent compound remained. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Use of early passage fetal intestinal epithelial cells in semi-high-throughput screening assays: an approach to identify new innate immune system adjuvants.

PubMed

Buckner, Diana; Wilson, Suzanne; Kurk, Sandra; Hardy, Michele; Miessner, Nicole; Jutila, Mark A

2006-09-01

Innate immune system stimulants (innate adjuvants) offer complementary approaches to vaccines and antimicrobial compounds to increase host resistance to infection. The authors established fetal bovine intestinal epithelial cell (BIEC) cultures to screen natural product and synthetic compound libraries for novel mucosal adjuvants. They showed that BIECs from fetal intestine maintained an in vivo phenotype as reflected in cytokeratin expression, expression of antigens restricted to intestinal enterocytes, and induced interleukin-8 (IL-8) production. BIECs could be infected by and support replication of bovine rotavirus. A semi-high-throughput enzyme-linked immunosorbent assay-based assay that measured IL-8 production by BIECs was established and used to screen commercially available natural compounds for novel adjuvant activity. Five novel hits were identified, demonstrating the utility of the assay for selecting and screening new epithelial cell adjuvants. Although the identified compounds had not previously been shown to induce IL-8 production in epithelial cells, other known functions for 3 of the 5 were consistent with this activity. Statistical analysis of the throughput data demonstrated that the assay is adaptable to a high-throughput format for screening both synthetic and natural product derived compound libraries.

Chemopreventive potential of natural compounds in head and neck cancer.

PubMed

Rahman, Mohammad Aminur; Amin, A R M Ruhul; Shin, Dong M

2010-01-01

Head and neck squamous cell carcinoma (HNSCC) is one of the most fatal cancers worldwide. Despite advances in the management of HNSCC, the overall survival for patients has not improved significantly due to advanced stages at diagnosis, high recurrence rate after surgical removal, and second primary tumor development, which underscore the importance of novel strategies for cancer prevention. Cancer chemoprevention, the use of natural or synthetic compounds to prevent, arrest, or reverse the process of carcinogenesis at its earliest stages, aims to reverse premalignancies and prevent second primary tumors. Genomics and proteomics information including initial mutation, cancer promotion, progression, and susceptibility has brought molecularly targeted therapies for drug development. The development of preventive approaches using specific natural or synthetic compounds, or both, requires a depth of understanding of the cross-talk between cancer signaling pathways and networks to retain or enhance chemopreventive activity while reducing known toxic effects. Many natural dietary compounds have been identified with multiple molecular targets, effective in the prevention and treatment of cancer. This review describes recent advances in the understanding of the complex signaling networks driving cancer progression and of molecularly targeted natural compounds under preclinical and clinical investigation.

Ultrasound-assisted synthesis, anticonvulsant activity, and docking study of indole-appended thiazolidin-4-ones.

PubMed

Nikalje, Anna Pratima G; Shaikh, Sameer I; Mulay, Abhineet; Khan, Firoz A K; Sangshetti, Jaiprakash N; Shaikh, Shoaib

2014-10-01

Two series of novel indolyl thiazolidin-4-one derivatives 4a-j and 5a-j were obtained by an ecofriendly synthetic protocol by treating a mixture of Schiff's bases (0.01 mol) with thioglycolic acid or thiolactic acid (0.01 mol) and anhydrous zinc chloride in catalytic amount in DMF as solvent under ultrasound irradiation, using an ultrasound synthesizer with a synthetic solid probe. The structures of the synthesized compounds were confirmed by IR, (1) H NMR, (13) C NMR, MS, and elemental analysis. The anticonvulsant activity and neurotoxicity of the newly synthesized compounds were established by MES and sc-PTZ model and by rotarod test, respectively, in vivo using mouse models. The actophotometer was used for the screening of behavioral activity. The compounds exhibited promising anticonvulsant activity; especially, the compounds showed maximum protection in the MES model at a dose of 100 mg/kg. Further, docking studies of the synthesized compounds were performed against the sodium channel receptor and showed good binding interactions with the receptor. A computational study was carried out to highlight the pharmacophore distance mapping, log p determination, and pharmacokinetic parameters. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enabling plant synthetic biology through genome engineering.

PubMed

Baltes, Nicholas J; Voytas, Daniel F

2015-02-01

Synthetic biology seeks to create new biological systems, including user-designed plants and plant cells. These systems can be employed for a variety of purposes, ranging from producing compounds of industrial or therapeutic value, to reducing crop losses by altering cellular responses to pathogens or climate change. To realize the full potential of plant synthetic biology, techniques are required that provide control over the genetic code - enabling targeted modifications to DNA sequences within living plant cells. Such control is now within reach owing to recent advances in the use of sequence-specific nucleases to precisely engineer genomes. We discuss here the enormous potential provided by genome engineering for plant synthetic biology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Screening for potential anti-infective agents towards Burkholderia pseudomallei infection

NASA Astrophysics Data System (ADS)

Eng, Su Anne; Nathan, Sheila

2014-09-01

The established treatment for melioidosis is antibiotic therapy. However, a constant threat to this form of treatment is resistance development of the causative agent, Burkholderia pseudomallei, towards antibiotics. One option to circumvent this threat of antibiotic resistance is to search for new alternative anti-infectives which target the host innate immune system and/or bacterial virulence. In this study, 29 synthetic compounds were evaluated for their potential to increase the lifespan of an infected host. The nematode Caenorhabditis elegans was adopted as the infection model as its innate immune pathways are homologous to humans. Screens were performed in a liquid-based survival assay containing infected worms exposed to individual compounds and survival of untreated and compound-treated worms were compared. A primary screen identified nine synthetic compounds that extended the lifespan of B. pseudomallei-infected worms. Subsequently, a disc diffusion test was performed on these selected compounds to delineate compounds into those that enhanced the survival of worms via antimicrobial activity i.e. reducing the number of infecting bacteria, or into those that did not target pathogen viability. Out of the nine hits selected, two demonstrated antimicrobial effects on B. pseudomallei. Therefore, the findings from this study suggest that the other seven identified compounds are potential anti-infectives which could protect a host against B. pseudomallei infection without developing the risk of drug resistance.

Synthetic chromanol derivatives and their interaction with complex III in mitochondria from bovine, yeast, and Leishmania.

PubMed

Monzote, L; Stamberg, W; Patel, A; Rosenau, T; Maes, L; Cos, P; Gille, L

2011-10-17

Synthetic chromanol derivatives (TMC4O, 6-hydroxy-2,2,7,8-tetramethyl-chroman-4-one; TMC2O, 6-hydroxy-4,4,7,8-tetramethyl-chroman-2-one; and Twin, 1,3,4,8,9,11-hexamethyl-6,12-methano-12H-dibenzo[d,g][1,3]dioxocin-2,10-diol) share structural elements with the potent inhibitor of the mitochondrial cytochrome (cyt) bc(1) complex stigmatellin. Studies with isolated bovine cyt bc(1) complex demonstrated that these compounds partially inhibit the mammalian enzyme. The aim of this work was to comparatively investigate these toxicological aspects of synthetic vitamin E derivatives in mitochondria of different species. The chromanols and atovaquone as reference compound were evaluated for their inhibition of the cyt bc(1) activity in mitochondrial fractions from bovine hearts, yeast, and Leishmania. In addition, compounds were evaluated in vitro for their inhibitory activity against whole-cell Leishmania and mouse peritoneal macrophages. In these organisms, the chromanols showed a species-selective inhibition of the cyt bc(1) activity different from that of atovaquone. While in atovaquone the side chain mediates species-selectivity, the marked differences for TMC2O and TMC4O in cyt bc(1) inhibition suggests that direct substitution of the chromanol headgroup will control selectivity in these compounds. Low micromolar concentrations of TMC2O (IC(50) = 9.5 ± 0.5 μM) inhibited the growth of Leishmania, and an esterified TMC2CO derivative inhibited the cyt bc(1) activity with an IC(50) of 4.9 ± 0.9 μM. These findings suggest that certain chromanols also exhibit beyond their antioxidative properties antileishmanial activities and that TMC2O derivatives could be useful toward the development of highly active antiprotozoal compounds.

A high-sensitivity ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) method for screening synthetic cannabinoids and other drugs of abuse in urine.

PubMed

Sundström, Mira; Pelander, Anna; Angerer, Verena; Hutter, Melanie; Kneisel, Stefan; Ojanperä, Ilkka

2013-10-01

The continuing emergence of designer drugs imposes high demands on the scope and sensitivity of toxicological drug screening procedures. An ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) method was developed for screening and simultaneous confirmation of both designer drugs and other drugs of abuse in urine samples in a single run. The method covered selected synthetic cannabinoids and cathinones, amphetamines, natural cannabinoids, opioids, cocaine and other important drugs of abuse, together with their main urinary metabolites. The database consisted of 277 compounds with molecular formula and exact monoisotopic mass; retention time was included for 192 compounds, and primary and secondary qualifier ion exact mass for 191 and 95 compounds, respectively. Following a solid-phase extraction, separation was performed by UHPLC and mass analysis by HR-TOFMS. MS, and broad-band collision-induced dissociation data were acquired at m/z range 50-700. Compound identification was based on a reverse database search with acceptance criteria for retention time, precursor ion mass accuracy, isotopic pattern and abundance of qualifier ions. Mass resolving power in spiked urine samples was on average FWHM 23,500 and mass accuracy 0.3 mDa. The mean and median cut-off concentrations determined for 75 compounds were 4.2 and 1 ng/mL, respectively. The range of cut-off concentrations for synthetic cannabinoids was 0.2-60 ng/mL and for cathinones 0.7-15 ng/mL. The method proved to combine high sensitivity and a wide scope in a manner not previously reported in drugs of abuse screening. The method's feasibility was demonstrated with 50 authentic urine samples.

Biomedically relevant circuit-design strategies in mammalian synthetic biology

PubMed Central

Bacchus, William; Aubel, Dominique; Fussenegger, Martin

2013-01-01

The development and progress in synthetic biology has been remarkable. Although still in its infancy, synthetic biology has achieved much during the past decade. Improvements in genetic circuit design have increased the potential for clinical applicability of synthetic biology research. What began as simple transcriptional gene switches has rapidly developed into a variety of complex regulatory circuits based on the transcriptional, translational and post-translational regulation. Instead of compounds with potential pharmacologic side effects, the inducer molecules now used are metabolites of the human body and even members of native cell signaling pathways. In this review, we address recent progress in mammalian synthetic biology circuit design and focus on how novel designs push synthetic biology toward clinical implementation. Groundbreaking research on the implementation of optogenetics and intercellular communications is addressed, as particularly optogenetics provides unprecedented opportunities for clinical application. Along with an increase in synthetic network complexity, multicellular systems are now being used to provide a platform for next-generation circuit design. PMID:24061539

Synthetic cannabinoids: the hidden side of Spice drugs.

PubMed

Pintori, Nicholas; Loi, Barbara; Mereu, Maddalena

2017-09-01

Spice drugs are herbal mixtures sprayed with synthetic cannabinoids designed to mimic the psychoactive ingredient in marijuana [Δ-tetrahydrocannabinol (Δ-THC)] and synthesized by introducing modifications to the chemical structure of parental compounds aiming to circumvent legal regulations. Synthetic cannabinoid use/abuse can be devastating as toxicological effects and adverse reactions cannot be entirely predicted and may vary with the dose, route of administration, individual vulnerability and concomitant intake with other drugs. The absence of validated testing procedures in the clinical field makes difficult the adoption of a therapeutic approach effective in coping with the synthetic cannabinoid phenomenon, posing a significant challenge for prevention, treatment and public health in general. The aim of this review is to gain insights into the epidemiological, pharmacological and toxicological properties of synthetic cannabinoids, aiming to provide a reliable background needed for the management of synthetic cannabinoid-related adverse effects. Consumers, competent authorities and medical care professionals should be aware of the risks associated with synthetic cannabinoid use.

Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.

PubMed

Neumann, Heinz; Neumann-Staubitz, Petra

2010-06-01

Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology.

Comparison of outcome expectancies for synthetic cannabinoids and botanical marijuana.

PubMed

Lauritsen, Kirstin J; Rosenberg, Harold

2016-07-01

Although initially developed for medical purposes, synthetic cannabinoids have also been consumed for recreational purposes. To evaluate whether agreement with positive and negative outcome expectancies differed for synthetic cannabinoids versus botanical marijuana, and assess reported reasons for using synthetic cannabinoids. Using a web-based recruitment and data collection procedure, 186 adults who had used both synthetic cannabinoids and botanical marijuana and 181 adults who had used botanical marijuana but not synthetic cannabinoids, completed measures of outcome expectancies and other relevant questionnaires. A significant interaction revealed that participants who had used both synthetic cannabinoids and botanical marijuana indicated lower agreement with positive expectancies for synthetic cannabinoids, and higher agreement with positive expectancies for botanical marijuana, than did those participants who used only botanical marijuana. There was no interaction between type of drug and use history on agreement with negative expectancies, and participants agreed more strongly with negative outcome expectancies for synthetic cannabinoids than for botanical marijuana whether they had used one or both types of these drugs. The most frequently provided reasons for using synthetic cannabinoids included availability, perceived legality, cost, curiosity, and social interaction. Given growing public acceptance of recreational and medical marijuana, coupled with negative perceptions and increasing regulation of synthetic cannabinoid compounds, botanical marijuana is likely to remain more available and more popular than synthetic cannabinoids.

"Word of mouse": indigenous harm reduction and online consumerism of the synthetic compound methoxphenidine.

PubMed

Van Hout, Marie Claire; Hearne, Evelyn

2015-01-01

Methoxphenidine (MXP) was one of several NMDA antagonists marketed in 2013 to replace the recently controlled compound Methoxetamine (MXE). A steep rise in user interest was recorded, despite vendor cautioning of limited user feedback. The study presented a phenomenological analysis of MXP experiences amongst recreational drug users as posted on public Internet fora. Internet searches were carried out using specific key words; "methoxphenidine," "MXP" and in combination with "experience," "report," "forum," and "trip." Seven self-reported experiences and 28 thread discussions relating sole use of MXP were analyzed using the Empirical Phenomenological Psychological method. Five themes and 61 categories emerged. MXP is marketed as a legal replacement for MXE, diphenidine, and ketamine, with a dissociative and stimulant wave outcome often lasting for days. Harm reduction tactics, awareness of prior tolerance to dissociative and optimal settings for use are discussed. Acute side-effects relate to hypertension and seizures. Chronic long-term memory loss and limb numbness is reported. Sense of empowerment occurs in the afterglow experience. Internet drug fora fuel information exchange and informed consumerism of synthetic compounds, and offer viable mechanisms for pre- and post-purchase decision making and indigenous harm reduction. Continued surveillance of synthetic market entries and user trends is warranted.

Aneugenic effects of benzoxazinones in cultured human cells.

PubMed

Arroyo, Elena; Chinchilla, Nuria; Molinillo, José M G; Macias, Francisco A; Astola, Antonio; Ortiz, Manuela; Valdivia, Manuel M

2010-01-01

Benzoxazinones (BAs) are natural products that are present in Gramineae and represent part of the plant defence system against pests. In recent years, sprouts of maize, wheat and rye have been used for the production of dietary supplements. We have investigated the potential genotoxic activities of a diverse range of synthetic derivatives of the most abundant natural BA, namely DIBOA (2,4-dihydroxy-1,4-benzoxazin-3-one), proposed for use as a potential herbicide. We have tested 18 synthetic BAs for potential effects in cultured HeLa cells. We found significantly higher micronucleus (MN) induction over the background level, with the solvent DMSO used as an internal control. Concentration-dependent effects were found between 1nM and 20nM for all the synthetic compounds studied. Immunostaining with an anticentromere antibody showed that >80% of MN induced gave a centromere-positive signal. Similarly, fluorescence in situ hybridization (FISH) analysis with alphoid centromere probes showed a positive hybridization signal, indicating that all compounds analyzed are aneugenic. Chemical modification of the N in the heterocyclic aromatic amine served us to suggest a relationship between the structure and the aneugenic effects of the compounds analyzed. Our findings indicate that benzoxazinoids could be potential genotoxins for human cells. Copyright 2009 Elsevier B.V. All rights reserved.

Inosine and 2'-deoxyinosine and their synthetic analogues: lipophilicity in the relation to their retention in reversed-phase liquid chromatography and the stability characteristics.

PubMed

Novotny, L; Abdel-Hamid, M; Hamza, H

2000-12-01

The purines and among them inosine synthetic nucleoside derivatives and analogues belong to a group of compounds to which the attention is being paid because of their biological activities. Relationships of their various parameters are being investigated because of their effect on biological (antineoplastic, virostatic, immunosuppressive) properties. Hydrophobicity parameters expressed as the logarithm of the partition coefficient (log P) and the capacity factor k' for naturally occurring inosine, 2'-deoxyinosine, 2'-deoxyadenosine and 2'-deoxyguanosine and for inosine synthetic analogues 5'-deoxyinosine, 5'-chloro-5'-deoxyinosine and 2',3'-dideoxyinosine were measured. The effect of methanol percentage in the mobile phase and its pH on the retention of the studied compounds in a reversed-phase system was also examined. There was a good correlation between the lipophilicity expressed as log P and capacity factor k'. It was also determined that dissociation has a marginal effect on capacity factor k' in this group of nucleoside derivatives as the k' values were almost unchanged at various pH of the mobile phase used. The stability of the all investigated compounds was investigated in basic, neutral and acidic conditions. The values of the reaction constant k1 were calculated and effects of nucleoside structural characteristic on stability are discussed.

Purity of synthetic cannabinoids sold online for recreational use.

PubMed

Ginsburg, Brett C; McMahon, Lance R; Sanchez, Jesus J; Javors, Martin A

2012-01-01

The recreational use of synthetic cannabinoids has recently increased. This increase is due, in part, to the recent availability of inexpensive compound sold legally online in bulk. In particular, JWH-018 (1-pentyl-3-(1-naphthoyl)indole) and JWH-073 (1-butyl-3-(1-naphthoyl)indole) have been found in herbal blends marketed as alternatives to cannabis. Although these particular compounds have recently been emergency scheduled in the United States, online suppliers have shifted sales to other, similar compounds that are not currently scheduled. However, the purity of the drugs obtained from online suppliers is not known. Relative purity of JWH-018 and JWH-073 from three different online suppliers was determined using high-performance liquid chromatography with ultraviolet detection and validated standards obtained from a traditional research chemical supplier. Our results show that JWH-018 and JWH-073 obtained from online vendors was of comparable purity to validated standards, even though the physical properties varied in color, texture, and odor. It is concluded that adverse events following consumption of synthetic cannabinoid preparations is unlikely to be due to impurities or residue from the manufacturing process, but rather to effects of the active drug or interactions with other psychoactive chemicals from herbs blended into products marketed as cannabis alternatives.

Biological activity of neosergeolide and isobrucein B (and two semi-synthetic derivatives) isolated from the Amazonian medicinal plant Picrolemma sprucei (Simaroubaceae).

PubMed

Silva, Ellen C C; Cavalcanti, Bruno C; Amorim, Rodrigo C N; Lucena, Jorcilene F; Quadros, Dulcimar S; Tadei, Wanderli P; Montenegro, Raquel C; Costa-Lotufo, Letícia V; Pessoa, Cláudia; Moraes, Manoel O; Nunomura, Rita C S; Nunomura, Sergio M; Melo, Marcia R S; Andrade-Neto, Valter F de; Silva, Luiz Francisco R; Vieira, Pedro Paulo R; Pohlit, Adrian M

2009-02-01

In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2), known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvicidal activity toward the dengue fever mosquito vector Aedes aegypti, haemolytic activity in mouse erythrocytes and antimalarial activity against the human malaria parasite Plasmodium falciparum. Compounds 1 and 2 exhibited the greatest cytotoxicity against all the tumor cells tested (IC50 = 5-27 microg/L) and against multidrug-resistant P. falciparum K1 strain (IC50 = 1.0-4.0 g/L) and 3 was only cytotoxic toward the leukaemia HL-60 strain (IC50 = 11.8 microg/L). Quassinoids 1 and 2 (LC50 = 3.2-4.4 mg/L) displayed greater lethality than derivative 4 (LC50 = 75.0 mg/L) toward A. aegypti larvae, while derivative 3 was inactive. These results suggest a novel application for these natural quassinoids as larvicides. The toxicity toward A. franciscana could be correlated with the activity in several biological models, a finding that is in agreement with the literature. Importantly, none of the studied compounds exhibited in vitro haemolytic activity, suggesting specificity of the observed cytotoxic effects. This study reveals the biological potential of quassinoids 1 and 2 and to a lesser extent their semi-synthetic derivatives for their in vitro antimalarial and cytotoxic activities.

[Drug Dependence and Cytotoxicity of Law-evading Drugs: Their Identities Explored from Basic Research].

PubMed

Funada, Masahiko

2016-01-01

  Cases of people experiencing disturbed consciousness or dyspnea, causing traffic accidents, or requiring ambulance transport to hospital due to abuse of law-evading chemical substances have become a serious social problem in Japan. Most law-evading herbal products are marketed as incense or herbs and consist of finely chopped, dry vegetative matter mixed with chemical substances (drugs). Analysis of the chemical substances in these herbal products has demonstrated that they contain synthetic cannabinoids. Because there are many cannabinoid compounds, even if a particular drug is regulated, similar compounds that differ only slightly in structure may be added in their place. Therefore a cat-and-mouse game exists between regulations on chemical substances and their propagation. This paper summarizes the pharmacological actions and dangers of chemical substances contained in law-evading herbal products by focusing on synthetic cannabinoids, as a group of chemical substances contained in these products. Furthermore, comprehensive designations of synthetic cannabinoids have been introduced as a new method of regulation that emphasizes the similarity of chemical structures; this paper also outlines the comprehensive designations. We established a psychic-dependence liability and cytotoxicity screening system for synthetic cannabinoids using animals (behavioral analysis in vivo) and cell cultures (cytotoxicity analysis in vitro). With our drug-screening system, we were able rapidly to evaluate and quantify psychic-dependence liabilities and cytotoxicity of synthetic cannabinoids contained in law-evading herbal products. These scientific data using our screening system contributed to the establishment of legislation for comprehensive designations of synthetic cannabinoids.

Nitrogen, Sulfur, and Oxygen Isotope Ratios of Animal- and Plant-Based Organic Fertilizers Used in South Korea.

PubMed

Shin, Woo-Jin; Ryu, Jong-Sik; Mayer, Bernhard; Lee, Kwang-Sik; Kim, Insu

2017-05-01

Organic fertilizers are increasingly used in agriculture in Asia and elsewhere. Tracer techniques are desirable to distinguish the fate of nutrients added to agroecosystems with organic fertilizers from those contained in synthetic fertilizers. Therefore, we determined the nitrogen, sulfur, and oxygen isotope ratios of nitrogen- and sulfur-bearing compounds in animal- and plant-based organic fertilizers (ABOF and PBOF, respectively) used in South Korea to evaluate whether they are isotopically distinct. The δN values of total and organic nitrogen for ABOF ranged from +7 to +19‰ and were higher than those of PBOF (generally <+6‰). This suggests that ABOFs have distinct δN values suitable for tracing these fertilizer compounds in the plant-soil-water system, whereas PBOFs have similar δN values to synthetic fertilizers. However, δO values for nitrate (δO) from organic fertilizer samples (<+17.0‰) were consistently lower than those of synthetic nitrate-containing fertilizers. The δS values of total sulfur, organic sulfur compounds (e.g., carbon-bonded sulfur and hydriodic acid-reducible sulfur), and sulfate for ABOFs yielded wide and overlapping ranges of +0.3 to +6.3, +0.9 to +7.2, and -2.6 to +14.2‰, whereas those for PBOFs varied from -3.4 to +7.7, +1.4 to +9.4, and -4.1 to +12.5‰, respectively, making it challenging to distinguish the fate of sulfur compounds from ABOF and PBOF in the environment using sulfur isotopes. We conclude that the δN values of ABOFs and the O values of organic fertilizers are distinct from those of synthetic fertilizers and are a promising tool for tracing the fate of nutrients added by organic fertilizers to agroecosystems. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

A comprehensive library-based, automated screening procedure for 46 synthetic cannabinoids in serum employing liquid chromatography-quadrupole ion trap mass spectrometry with high-temperature electrospray ionization.

PubMed

Huppertz, Laura M; Kneisel, Stefan; Auwärter, Volker; Kempf, Jürgen

2014-02-01

Considering the vast variety of synthetic cannabinoids and herbal mixtures - commonly known as 'Spice' or 'K2' - on the market and the resulting increase of severe intoxications related to their consumption, there is a need in clinical and forensic toxicology for comprehensive up-to-date screening methods. The focus of this project aimed at developing and implementing an automated screening procedure for the detection of synthetic cannabinoids in serum using a liquid chromatography-ion trap-MS (LC-MS(n)) system and a spectra library-based approach, currently including 46 synthetic cannabinoids and 8 isotope labelled analogues. In the process of method development, a high-temperature ESI source (IonBooster(TM), Bruker Daltonik) and its effects on the ionization efficiency of the investigated synthetic cannabinoids were evaluated and compared to a conventional ESI source. Despite their structural diversity, all investigated synthetic cannabinoids benefitted from high-temperature ionization by showing remarkably higher MS intensities compared to conventional ESI. The employed search algorithm matches retention time, MS and MS(2)/MS(3) spectra. With the utilization of the ionBooster source, limits for the automated detection comparable to cut-off values of routine MRM methods were achieved for the majority of analytes. Even compounds not identified when using a conventional ESI source were detected using the ionBooster-source. LODs in serum range from 0.1 ng/ml to 0.5 ng/ml. The use of parent compounds as analytical targets offers the possibility of instantly adding new emerging compounds to the library and immediately applying the updated method to serum samples, allowing the rapid adaptation of the screening method to ongoing forensic or clinical requirements. The presented approach can also be applied to other specimens, such as oral fluid or hair, and herbal mixtures and was successfully applied to authentic serum samples. Quantitative MRM results of samples with analyte concentrations above the determined LOD were confirmed as positive findings by the presented method. Copyright © 2014 John Wiley & Sons, Ltd.

50 CFR 100.25 - Subsistence taking of fish, wildlife, and shellfish: general regulations.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., Sitka black-tailed deer, elk, mountain goat, moose, musk ox, Dall sheep, wolf, and wolverine. Bow means..., wolf, or wolverine. Fyke net means a fixed, funneling (fyke) device used to entrap fish. Gear means any... wildlife as food for a dog or furbearer, or as bait, except as allowed for in § 100.26, § 100.27, or § 100...

50 CFR 100.25 - Subsistence taking of fish, wildlife, and shellfish: general regulations.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., Sitka black-tailed deer, elk, mountain goat, moose, musk ox, Dall sheep, wolf, and wolverine. Bow means..., wolf, or wolverine. Fyke net means a fixed, funneling (fyke) device used to entrap fish. Gear means any... wildlife as food for a dog or furbearer, or as bait, except as allowed for in § 100.26, § 100.27, or § 100...

SpaceX: Breaking the Barrier to the Space Launch Vehicle Industry

DTIC Science & Technology

2016-12-22

like FedEx, implemented a unique technique to the industry and found success. SpaceX was also evaluated against guidelines and principles presented by...associated with implementing vertical integration. Musk, following value innovative principles , is using the concept of reusability to decrease the...47 Figure 6: Vertical Integration, Relative Market Share, and Profitability (Buzzell, 1983) ...... 49 Figure 7. SpaceX Capabilities and

Tailored Organometallic Polymers

DTIC Science & Technology

1993-01-31

2-4). These synthetic pathways provide access to a wide variety of new silicon compounds for use as reagents in organic syntheses and the electronics...34Si0 2 as a Source of Si Containing Compounds / Polymers", D.J. Ray, R.M. Laine, C. Viney and T.R. Robinson, ACS Polymer Preprints (1991) 32(3), 550...3) as precursors to orgar.osilicon compounds .[10-12] Pentacoordinate silicates are easily prepa’ed frotv tetrasubstituted Si centers containing

Photochemical transformations of diazocarbonyl compounds: expected and novel reactions

NASA Astrophysics Data System (ADS)

Galkina, O. S.; Rodina, L. L.

2016-05-01

Photochemical reactions of diazocarbonyl compounds are well positioned in synthetic practice as an efficient method for ring contraction and homologation of carboxylic acids and as a carbene generation method. However, interpretation of the observed transformations of diazo compounds in electronically excited states is incomplete and requires a careful study of the fine mechanisms of these processes specific to different excited states of diazo compounds resorting to modern methods of investigation, including laser technology. The review is devoted to analysis of new data in the chemistry of excited states of diazocarbonyl compounds. The bibliography includes 155 references.

40 CFR 60.666 - Reconstruction.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Distillation Operations § 60.666...

40 CFR 60.662 - Standards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Distillation Operations § 60.662...

40 CFR 60.662 - Standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Distillation Operations § 60.662...

40 CFR 60.662 - Standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Distillation Operations § 60.662...

40 CFR 60.666 - Reconstruction.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Distillation Operations § 60.666...

Application of bicyclic and cage compounds

NASA Technical Reports Server (NTRS)

Clark, R. D.; Archuleta, B. S.

1976-01-01

The results of a literature survey of the field of bicyclic and cage compounds were presented, with the objective of identifying those types of compounds with unusual physical and chemical stability, and determining what practical applications have been found for these compounds. Major applications have been as polymers, polymer additives, medicinals, and pesticides. Lesser applications have included fuels, fuel additives, lubricants, lubricant additives, and perfumes. Several areas where further work might be useful were also outlined; these are primarily in the areas of polymers, polymer additives, medicinals, and synthetic lubricants.

Synthesis and odor evaluation of five new sulfur-containing ester flavor compounds from 4-ethyloctanoic acid.

PubMed

Liu, Yuping; Chen, Haitao; Yin, Decai; Sun, Baoguo

2010-07-29

Five sulfur-containing flavor compounds were synthesized for the first time by the reaction of 4-ethyloctanoyl chloride with sulfur-containing alcohols or mercaptans. The synthesized compounds are 3-(methylthio)propyl 4-ethyloctanoate, 2-methyl-3-tetrahydro-furanthiol 4-ethyloctanoate, 4-methyl-5-thiazoleethanol 4-ethyloctanoate, 2-furan-methanethiol 4-ethyloctanoate and 2-methyl-3-furanthiol 4-ethyloctanoate. These five synthetic sulfur-containing ester flavor compounds all have meaty odor and might be used in foods if approved for this purpose in the future.

40 CFR 60.668 - Delegation of authority.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Distillation Operations...

40 CFR 60.668 - Delegation of authority.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound (VOC) Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Distillation Operations...

Thiadiazole derivatives as New Class of β-glucuronidase inhibitors.

PubMed

Salar, Uzma; Taha, Muhammad; Ismail, Nor Hadiani; Khan, Khalid Mohammed; Imran, Syahrul; Perveen, Shahnaz; Wadood, Abdul; Riaz, Muhammad

2016-04-15

Thiadiazole derivatives 1-24 were synthesized via a single step reaction and screened for in vitro β-glucuronidase inhibitory activity. All the synthetic compounds displayed good inhibitory activity in the range of IC50=2.16 ± 0.01-58.06 ± 1.60 μM as compare to standard d-saccharic acid 1,4-lactone (IC50=48.4 ± 1.25 μM). Molecular docking study was conducted in order to establish the structure-activity relationship (SAR) which demonstrated that thiadiazole as well as both aryl moieties (aryl and N-aryl) involved to exhibit the inhibitory potential. All the synthetic compounds were characterized by spectroscopic techniques (1)H, (13)C NMR, and EIMS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis of the biologically active natural product cyclodepsipeptides apratoxin A and its analogues.

PubMed

Doi, Takayuki

2014-01-01

This paper describes the synthetic studies conducted on a marine natural product, cyclodepsipeptide apratoxin A. Total synthesis of the oxazoline analogue of apratoxin A was achieved. The conversion of oxazoline to thioamide, as well as thioamide formation from a serine-derived compound, were both unsuccessful. However, thiazoline formation from a cysteine-derived compound led to the total synthesis of apratoxin A. An in vivo study on synthetic apratoxin A revealed that it has potent antitumor activity, but with significant toxicity. Solid-phase synthesis of apratoxin A was accomplished using a preformed thiazoline derivative as a coupling unit. This method was used to synthesize several azido-containing analogues as precursors of molecular probes, and these analogues exhibited potent biological activity.

The antioxidant activity of some curcuminoids and chalcones.

PubMed

Sökmen, Münevver; Akram Khan, M

2016-06-01

The antioxidant properties of the synthetic compound (C1)-(C8), which comprised 7 curcuminoids and a chalcone, were evaluated by two complementary assays, DPPH and β-carotene/linoleic acid. It was found that, in general, the free radical scavenging ability of (C1)-(C8) was concentration-dependent. Compounds (C1) and (C4), which contained (4-OH) phenolic groups, were found to be highly potent antioxidants with higher antioxidant values than BHT suggesting that synthetic curcuminoids are more potent antioxidants than standard antioxidants like BHT. Using β-carotene-linoleic acid assay, only the water-soluble 2, 4,6-trihydroxyphenolic chalcone (C5) showed 85.2 % inhibition of the formation of conjugated dienes reflecting on its potent antioxidant activity.

Compound 9a, a novel synthetic histone deacetylase inhibitor, protects against septic injury in mice by suppressing MAPK signalling

PubMed Central

Kim, So‐Jin; Baek, Ki Seon; Park, Hyun‐Ju; Jung, Young Hoon

2016-01-01

Background and Purpose Sepsis is a life‐threatening clinical condition characterized by uncontrolled inflammatory responses and is a major cause of death in intensive care units. Histone deacetylase (HDAC) inhibitors have recently exhibited anti‐inflammatory properties. MAPK phosphatase (MKP) suppresses MAPK signalling, which plays an important role in inflammatory responses. The purpose of this study was to investigate the protective mechanisms of Compound 9a, a newly synthetized HDAC inhibitor, against septic injury. Experimental Approach The anti‐inflammatory properties of Compound 9a were assayed in LPS‐stimulated RAW264.7 cells. In vivo, polymicrobial sepsis was induced in C57BL/6 mice by caecal ligation and puncture (CLP). The mice were treated with Compound 9a (i.p., 10 mg∙kg−1) 2 h before and immediately after CLP. Key Results Compound 9a inhibited the increased production of TNF‐α, IL‐6 and NO in LPS‐stimulated RAW264.7 cells. In mice with CLP, Compound 9a improved survival rate, attenuated organ injuries and decreased serum TNF‐α and IL‐6 levels. CLP increased expression of toll‐like receptor 4, phosphorylated (p)‐p38, p‐JNK and p‐ERK proteins, which was attenuated by Compound 9a. Compound 9a decreased MKP‐1 association with HDAC1 and enhanced MKP‐1 acetylation and enhanced MKP‐1 association with p‐p38 and p‐ERK. Moreover, the inhibitory effects of Compound 9a on serum cytokine levels and phosphorylation of MAPK were abolished by MKP‐1 siRNA. Conclusions and Implications Our findings suggest that Compound 9a protected against septic injury by suppressing MAPK‐mediated inflammatory signalling. PMID:26689981

Vadose zone transport of natural and synthetic estrogen hormones at Penn State's "Living Filter" wastewater irrigation site

USDA-ARS?s Scientific Manuscript database

The increase in endocrine disrupting compounds (EDCs) in the environment has generated new research focused on the behavior of these compounds in natural soil and water ecosystems. To understand how estrogens behave in the soil environment as a result of 25+ years of wastewater irrigation, soils fro...

The most frequently encountered volatile contaminants of essential oils and plant extracts introduced during the isolation procedure: fast and easy profiling.

PubMed

Radulović, Niko S; Blagojević, Polina D

2012-01-01

Unfortunately, contaminants of synthetic/artificial origin are sometimes identified as major constituents of essential oils or plant extracts and considered to be biologically active native plant metabolites. To explore the possibility of early recognition and to create a list of some of the most common semi-volatile contaminants of essential oils and plant extracts. Detailed GC and GC-MS analyses of the evaporation residues of six commercially available diethyl ethers and of a plastic bag hydrodistillate were performed. Average mass scans of the total ion chromatogram profiles of the analysed samples were performed. Almost 200 different compounds, subdivided into two groups, were identified in the analysed samples: (i) compounds that could be only of a synthetic/artificial origin, such as butylated hydroxytoluene and o-phthalic acid esters, i.e. requiring exclusion from the list of identified plant constituents; (ii) compounds possibly of synthetic and/or natural plant origin, i.e. compounds derived from the fatty acid metabolism or products of anaerobic intracellular/microbial fermentation. Average mass scans of the total ion chromatogram profiles provide meaningful and convenient information on uncovering important solvent-derived contamination. A database of the most common semi-volatile contaminants of essential oils and plant extracts has been generated that provides information on the likelihood of rejection or acceptance of contaminants as possible plant constituents. The suggested average mass scan approach enables fast and easy profiling of solvents, allowing even inexperienced researchers to pinpoint contaminants. Copyright © 2011 John Wiley & Sons, Ltd.

Inhibitors of pancreatic lipase: state of the art and clinical perspectives

PubMed Central

Lunagariya, Nitin A.; Patel, Neeraj K.; Jagtap, Sneha C.; Bhutani, Kamlesh K.

2014-01-01

Obesity is a disorder of lipid metabolism and continues to be a global problem, ranking fifth for deaths worldwide. It also leads to diabetes, cardiovascular disorders, musculoskeletal disorders and some types of cancer. Obesity is regarded as the output of a long-term imbalance between energy intake and energy expenditure. Digestion and absorption of dietary lipids by pancreatic lipase, a major source of excess calorie intake, can be targeted for development of anti-obesity agents. Being the major factor of concern, food materials and edible plants are most widely studied for the anti-obesity activity, so that they can be incorporated in the routine diet. In this review, an attempt was made to present a current scenario of the bioactive compounds from plant and microbial origin that have been investigated for their pancreatic lipase inhibition. Compounds belonging to various classes of natural products such as alkaloids, carotenoids, glycosides, polyphenols, polysaccharides, saponins and terpenoids are well studied while lipophilic compounds from microbial sources are the most active against the pancreatic lipase. Few studies on the synthetic analogues, structurally similar to the triglycerides have been described in the review. Despite of tremendous research on the finding of potential pancreatic lipase inhibitor, very few compounds have entered the clinical studies and no new molecule after orlistat has been marketed. Along with HTS based screening, detailed structure-activity relationship studies on semi-synthetic and synthetic derivatives might also provide a direction for the development of potential lead(s) or pharmacophore for pancreatic lipase inhibition in order to treat and/or prevent obesity and related disorders. PMID:26417311

BIOCHEMICAL INDICATORS OF HEPATOTOXICITY IN BLOOD SERUM OF RATS UNDER THE EFFECT OF NOVEL 4-THIAZOLIDINONE DERIVATIVES AND DOXORUBICIN AND THEIR COMPLEXES WITH POLYETHYLENEGLYCOL-CONTAINING NANOSCALE POLYMERIC CARRIER.

PubMed

Kobylinska, L I; Havrylyuk, D Ya; Ryabtseva, A O; Mitina, N E; Zaichenko, O S; Lesyk, R B; Zimenkovsky, B S; Stoika, R S

2015-01-01

The aim of this study was to compare the effect of new synthetic 4-tiazolidinone derivatives (compounds 3882, 3288 and 3833) and doxorubicin (positive control) in free form and in their complexes with synthetic polyethyleneglycol-containing nanoscale polymeric carrier on the biochemical indicators of hepatotoxicity in blood serum of rats. The activity of enzymes considered as the markers of hepatotoxicity, as well as. the concentration of total protein, urea and creatinine were measured in blood serum of rats. It was found that after injection of investigated compounds the activities ofalanine aminotransferase, alkaline phosphatase and α-amylase increased in comparison to control. Doxorubicin injection was accompanied by 4-fold increase in the activity of γ-glutamyltransferase, and injection ofcompound 3833 led to 2.5-fold elevation ofthe activity of this enzyme. Complexation ofthese antineoplastic derivatives with a synthetic nanocarrier lowered the activity ofthe investigated enzymes substantially if compared to the effect of these compounds infreeform. The most evident decrease was measured for α-amylase, γ-glutamyltransferase and lactate dehydrogenase activities. The normalization of concentrations of total protein, urea and creatinine in blood serum of rats treated with complexes of the studied compounds with a polymeric carrier comparing with their introduction infreeform was also detected. Thus, the immobilization by novel polymeric carrier of anticancer drugs possessing high general toxicity in the treated organism mitigates their toxic effect, which is evident as normalization of specific biochemical indicators of the hepatodestructive effects of the anticancer drugs.

A concise entry into nonsymmetrical alkyl polyamines.

PubMed

Pirali, Tracey; Callipari, Grazia; Ercolano, Emanuela; Genazzani, Armando A; Giovenzana, Giovanni Battista; Tron, Gian Cesare

2008-10-02

The synthesis of nonsymmetrical polyamines (PAs) has, up to now, been problematic due to lengthy synthetic procedures, lack of regioselectivity, and very poor atom economy. An innovative synthetic protocol for nonsymmetrical PAs using a modified Ugi reaction ( N-split Ugi) which simplifies the synthesis of these tricky compounds is described. We believe that this new synthesis may open the door for the generation of new and pharmacologically active PAs.

40 CFR 60.702 - Standards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor Processes § 60.702 Standards. Each owner...

40 CFR 60.702 - Standards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor Processes § 60.702 Standards. Each owner...

40 CFR 60.706 - Reconstruction.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor Processes § 60.706 Reconstruction. (a) For...

40 CFR 60.706 - Reconstruction.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor Processes § 60.706 Reconstruction. (a) For...

Legendary Chemical Aphrodisiacs.

ERIC Educational Resources Information Center

Waddell, Thomas G.; And Others

1980-01-01

Presents a survey of the literature and a summary of information regarding aphrodisiacs. Chemical compounds are discussed as groups of plant natural products, animal natural products, and synthetic products. (CS)

Synthetic anabolic agents: steroids and nonsteroidal selective androgen receptor modulators.

PubMed

Thevis, Mario; Schänzer, Wilhelm

2010-01-01

The central role of testosterone in the development of male characteristics, as well as its beneficial effects on physical performance and muscle growth, has led to the search for synthetic alternatives with improved pharmacological profiles. Hundreds of steroidal analogs have been prepared with a superior oral bioavailability, which should also possess reduced undesirable effects. However, only a few entered the pharmaceutical market due to severe toxicological incidences that were mainly attributed to the lack of tissue selectivity. Prominent representatives of anabolic-androgenic steroids (AAS) are for instance methyltestosterone, metandienone and stanozolol, which are discussed as model compounds with regard to general pharmacological aspects of synthetic AAS. Recently, nonsteroidal alternatives to AAS have been developed that selectively activate the androgen receptor in either muscle tissue or bones. These so-called selective androgen receptor modulators (SARMs) are currently undergoing late clinical trials (IIb) and will be prohibited by the World Anti-Doping Agency from January 2008. Their entirely synthetic structures are barely related to steroids, but particular functional groups allow for the tissue-selective activation or inhibition of androgen receptors and, thus, the stimulation of muscle growth without the risk of severe undesirable effects commonly observed in steroid replacement therapies. Hence, these compounds possess a high potential for misuse in sports and will be the subject of future doping control assays.

Cuticular hydrocarbons as sex pheromone of the bee Colletes cunicularius and the key to its mimicry by the sexually deceptive orchid, Ophrys exaltata.

PubMed

Mant, Jim; Brändli, Christoph; Vereecken, Nicolas J; Schulz, Claudia M; Francke, Wittko; Schiestl, Florian P

2005-08-01

Male Colletes cunicularius bees pollinate the orchid, Ophrys exaltata, after being sexually deceived by the orchid's odor-mimicry of the female bee's sex pheromone. We detected biologically active volatiles of C. cunicularius by using gas chromatographic-electroantennographic detection (GC-EAD) with simultaneous flame ionization detection. After identification of the target compounds by coupled gas chromatography mass spectrometry (GC-MS), we performed behavioral tests using synthetic blends of the active components. We detected 22 EAD active compounds in cuticular extracts of C. cunicularius females. Blends of straight chain, odd-numbered alkanes and (Z)-7-alkenes with 21-29 carbon atoms constituted the major biologically active compounds. Alkenes were the key compounds releasing mating behavior, especially those with (Z)-7 unsaturation. Comparison of patterns of bee volatiles with those of O. exaltata subsp. archipelagi revealed that all EAD-active compounds were also found in extracts of orchid labella. Previous studies of the mating behavior in C. cunicularius showed linalool to be an important attractant for patrolling males. We confirmed this with synthetic linalool but found that it rarely elicited copulatory behavior, in accordance with previous studies. A blend of active cuticular compounds with linalool elicited both attraction and copulation behavior in patrolling males. Thus, linalool appears to function as a long-range attractant, whereas cuticular hydrocarbons are necessary for inducing short-range mating behavior.

Resveratrol, piceatannol and analogs inhibit activation of both wild-type and T877A mutant androgen receptor.

PubMed

Lundqvist, Johan; Tringali, Corrado; Oskarsson, Agneta

2017-11-01

Prostate cancer growth and progression are mainly dependent on androgens and many current prostate cancer treatment options target the synthesis or function of androgens. We have previously reported that resveratrol and synthetic analogs of resveratrol with a higher bioavailability inhibit the synthesis of androgens in human adrenocortical H295R cells. Now we have studied the antiandrogenic properties of resveratrol, piceatannol and analogs in two different prostate cell lines; LNCaP and RWPE. LNCaP carry a T877A mutation in the androgen receptor while RWPE has a wild-type androgen receptor. We found that resveratrol, piceatannol and all studied analogs were able to inhibit a dihydrotestosterone-induced activation of the androgen receptor, showing that they act as antiandrogens. In LNCaP cells, all studied compounds were able to statistically significantly decrease the androgenic signaling in concentrations ≥1μM and the synthetic analogs trimethylresveratrol (RSVTM) and tetramethylpiceatannol (PICTM) were the most potent compounds. RWPE cells were not as responsive to the studied compounds as the LNCaP cells. A statistically significant decrease in the androgenic signaling was observed at concentrations ≤5μM for most compounds and RSVTM was found to be the most potent compound. Further, we studied the effects of resveratrol, piceatannol and analogs on the levels of prostate-specific antigen (PSA) in LNCaP cells and found that all studied compounds decreased the level of PSA and that the synthetic analogs diacetylresveratrol (RSVDA), triacetylresveratrol (RSVTA) and RSVTM were the most potent compounds, decreasing the PSA level by approx. 50% at concentrations ≥10μM. In a cell-free receptor binding assay we were unable to show binding of resveratrol or analogs to the ligand binding domain of the androgen receptor, indicating that the observed effects are mediated via other mechanisms than direct ligand competition. We conclude that the resveratrol, piceatannol and analogs are highly interesting for chemoprevention of prostate cancer, since they have a high potency both as inhibitors of androgen synthesis and androgen receptor activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spatio-temporal evaluation of organic contaminants and their transformation products along a river basin affected by urban, agricultural and industrial pollution.

PubMed

Gómez, María José; Herrera, Sonia; Solé, David; García-Calvo, Eloy; Fernández-Alba, Amadeo R

2012-03-15

This study aims to assess the occurrence, fate and temporal and spatial distribution of anthropogenic contaminants in a river subjected to different pressures (industrial, agricultural, wastewater discharges). For this purpose, the Henares River basin (central Spain) can be considered a representative basin within a continental Mediterranean climate. As the studied river runs through several residential, industrial and agricultural areas, it would be expected that the chemical water quality is modified along its course. Thereby the selection of sampling points and timing of sample collection are critical factors in the monitoring of a river basin. In this study, six different monitoring campaigns were performed in 2010 and contaminants were measured at the effluent point of the main wastewater treatment plant (WWTP) in the river basin and at five different points upstream and downstream from the WWTP emission point. The target compounds evaluated were personal care products (PCPs), polycyclic aromatic hydrocarbons (PAHs) and pesticides. Results show that the river is clearly influenced by wastewater discharges and also by its proximity to agricultural areas. The contaminants detected at higher concentrations were the PCPs. The spatial distribution of the contaminants indicates that the studied contaminants persist along the river. In the time period studied no great seasonal variations of PCPs at the river collection points were observed. In contrast, a temporal trend of pesticides and PAHs was observed. Besides the target compounds, other new contaminants were identified and evaluated in the water samples, some of them being investigated for the first time in the aquatic environment. The behaviour of three important transformation products was also evaluated: 9,10-anthracenodione, galaxolide-lactone and 4-amino-musk xylene. These were found at higher concentrations than their parent compounds, indicating the significance of including the study of transformation products in the monitoring programmes. Copyright © 2012 Elsevier B.V. All rights reserved.

Removal of pharmaceutical and personal care products (PPCPs) under nitrifying and denitrifying conditions.

PubMed

Suarez, Sonia; Lema, Juan M; Omil, Francisco

2010-05-01

The contribution of volatilization, sorption and transformation to the removal of 16 Pharmaceutical and Personal Care Products (PPCPs) in two lab-scale conventional activated sludge reactors, working under nitrifying (aerobic) and denitrifying (anoxic) conditions for more than 1.5 years, have been assessed. Pseudo-first order biological degradation rate constants (k(biol)) were calculated for the selected compounds in both reactors. Faster degradation kinetics were measured in the nitrifying reactor compared to the denitrifying system for the majority of PPCPs. Compounds could be classified according to their k(biol) into very highly (k(biol)>5Lg(SS)(-1)d(-1)), highly (175%) and anoxic (>65%) conditions, whereas naproxen (NPX), ethinylestradiol (EE2), roxithromycin (ROX) and erythromycin (ERY) were only significantly transformed in the aerobic reactor (>80%). The anti-depressant citalopram (CTL) was moderately biotransformed under both, aerobic and anoxic conditions (>60% and >40%, respectively). Some compounds, as carbamazepine (CBZ), diazepam (DZP), sulfamethoxazole (SMX) and trimethoprim (TMP), manifested high resistance to biological transformation. Solids Retention Time (SRT(aerobic) >50d and <50d; SRT(anoxic) >20d and <20d) had a slightly positive effect on the removal of FLX, NPX, CTL, EE2 and natural estrogens (increase in removal efficiencies <10%). Removal of diclofenac (DCF) in the aerobic reactor was positively affected by the development of nitrifying biomass and increased from 0% up to 74%. Similarly, efficient anoxic transformation of ibuprofen (75%) was observed after an adaptation period of 340d. Temperature (16-26 degrees C) only had a slight effect on the removal of CTL which increased in 4%.

Chemopreventive potential of natural compounds in head and neck cancer

PubMed Central

Rahman, Mohammad Aminur; Amin, A.R.M. Ruhul; Shin, Dong M.

2013-01-01

Head and neck squamous cell carcinoma (HNSCC) is one of the most fatal cancers world-wide. Despite advances in the management of HNSCC, the overall survival for patients has not improved significantly due to advanced stages at diagnosis, high recurrence rate after surgical removal, and second primary tumor development, which together underscore the importance of novel strategies for cancer prevention. Cancer chemoprevention, the use of natural or synthetic compounds to prevent, arrest, or reverse the process of carcinogenesis at its earliest stages, aims to reverse premalignancies and prevent second primary tumors. Genomics and proteomics information including initial mutation, cancer promotion, progression and susceptibility has brought molecularly targeted therapies for drug development. The development of preventive approaches using specific natural or synthetic compounds, or both, requires a depth of understanding of the cross-talk between cancer signaling pathways and networks to retain or enhance chemopreventive activity while reducing known toxic effects. Many natural dietary compounds have been identified as multiple molecular targets, effective in the prevention and treatment of cancer. This review describes recent advances in the understanding of the complex signaling networks driving cancer progression using head and neck cancer as a prototype, and of molecularly targeted natural compounds under preclinical and clinical investigation. PMID:20924973

New approaches to antimicrobial discovery.

PubMed

Lewis, Kim

2017-06-15

The spread of resistant organisms is producing a human health crisis, as we are witnessing the emergence of pathogens resistant to all available antibiotics. An increase in chronic infections presents an additional challenge - these diseases are difficult to treat due to antibiotic-tolerant persister cells. Overmining of soil Actinomycetes ended the golden era of antibiotic discovery in the 60s, and efforts to replace this source by screening synthetic compound libraries was not successful. Bacteria have an efficient permeability barrier, preventing penetration of most synthetic compounds. Empirically establishing rules of penetration for antimicrobials will form the knowledge base to produce libraries tailored to antibiotic discovery, and will revive rational drug design. Two untapped sources of natural products hold the promise of reviving natural product discovery. Most bacterial species, over 99%, are uncultured, and methods to grow these organisms have been developed, and the first promising compounds are in development. Genome sequencing shows that known producers harbor many more operons coding for secondary metabolites than we can account for, providing an additional rich source of antibiotics. Revival of natural product discovery will require high-throughput identification of novel compounds within a large background of known substances. This could be achieved by rapid acquisition of transcription profiles from active extracts that will point to potentially novel compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

Lead-oriented synthesis: Investigation of organolithium-mediated routes to 3-D scaffolds and 3-D shape analysis of a virtual lead-like library.

PubMed

Lüthy, Monique; Wheldon, Mary C; Haji-Cheteh, Chehasnah; Atobe, Masakazu; Bond, Paul S; O'Brien, Peter; Hubbard, Roderick E; Fairlamb, Ian J S

2015-06-01

Synthetic routes to six 3-D scaffolds containing piperazine, pyrrolidine and piperidine cores have been developed. The synthetic methodology focused on the use of N-Boc α-lithiation-trapping chemistry. Notably, suitably protected and/or functionalised medicinal chemistry building blocks were synthesised via concise, connective methodology. This represents a rare example of lead-oriented synthesis. A virtual library of 190 compounds was then enumerated from the six scaffolds. Of these, 92 compounds (48%) fit the lead-like criteria of: (i) -1⩽AlogP⩽3; (ii) 14⩽number of heavy atoms⩽26; (iii) total polar surface area⩾50Å(2). The 3-D shapes of the 190 compounds were analysed using a triangular plot of normalised principal moments of inertia (PMI). From this, 46 compounds were identified which had lead-like properties and possessed 3-D shapes in under-represented areas of pharmaceutical space. Thus, the PMI analysis of the 190 member virtual library showed that whilst scaffolds which may appear on paper to be 3-D in shape, only 24% of the compounds actually had 3-D structures in the more interesting areas of 3-D drug space. Copyright © 2015 Elsevier Ltd. All rights reserved.

β-Lactam Ring Opening: A Useful Entry to Amino Acids and Relevant Nitrogen-Containing Compounds

NASA Astrophysics Data System (ADS)

Palomo, C.; Oiarbide, M.

The main strategies for the ring opening of β-lactams by chemical means are described. The discovery of each approach is put into context, sometimes in connection to processes occurring in biological systems, and the synthetic opportunities each approach offers are shown. Thus, this β-lactam route affords a number of synthetically relevant building-blocks, including α-amino acids, β-amino acids, their derived peptides, and other nitrogen containing heterocycles and open chain molecules. The content, which encompases references to initial work, further major development, and the most relevant recent literature contributions, is categorized according to the ring bond cleavaged (N 1-C 2, C 2-C 3, C 3 -C 4 , N 1-C 4), to finish with ring opening strategies leading to large heterocyclic compounds. Within each category, distinction has been made according to the type of nucleophilic agent employed, principally O-, N-, and C-nucleophiles. Also, a variety of applications of the strategy to the synthesis of interesting target compounds are shown.

Miscellaneous Topics in Computer-Aided Drug Design: Synthetic Accessibility and GPU Computing, and Other Topics.

PubMed

Fukunishi, Yoshifumi; Mashimo, Tadaaki; Misoo, Kiyotaka; Wakabayashi, Yoshinori; Miyaki, Toshiaki; Ohta, Seiji; Nakamura, Mayu; Ikeda, Kazuyoshi

2016-01-01

Computer-aided drug design is still a state-of-the-art process in medicinal chemistry, and the main topics in this field have been extensively studied and well reviewed. These topics include compound databases, ligand-binding pocket prediction, protein-compound docking, virtual screening, target/off-target prediction, physical property prediction, molecular simulation and pharmacokinetics/pharmacodynamics (PK/PD) prediction. Message and Conclusion: However, there are also a number of secondary or miscellaneous topics that have been less well covered. For example, methods for synthesizing and predicting the synthetic accessibility (SA) of designed compounds are important in practical drug development, and hardware/software resources for performing the computations in computer-aided drug design are crucial. Cloud computing and general purpose graphics processing unit (GPGPU) computing have been used in virtual screening and molecular dynamics simulations. Not surprisingly, there is a growing demand for computer systems which combine these resources. In the present review, we summarize and discuss these various topics of drug design.

Miscellaneous Topics in Computer-Aided Drug Design: Synthetic Accessibility and GPU Computing, and Other Topics

PubMed Central

Fukunishi, Yoshifumi; Mashimo, Tadaaki; Misoo, Kiyotaka; Wakabayashi, Yoshinori; Miyaki, Toshiaki; Ohta, Seiji; Nakamura, Mayu; Ikeda, Kazuyoshi

2016-01-01

Abstract: Background Computer-aided drug design is still a state-of-the-art process in medicinal chemistry, and the main topics in this field have been extensively studied and well reviewed. These topics include compound databases, ligand-binding pocket prediction, protein-compound docking, virtual screening, target/off-target prediction, physical property prediction, molecular simulation and pharmacokinetics/pharmacodynamics (PK/PD) prediction. Message and Conclusion: However, there are also a number of secondary or miscellaneous topics that have been less well covered. For example, methods for synthesizing and predicting the synthetic accessibility (SA) of designed compounds are important in practical drug development, and hardware/software resources for performing the computations in computer-aided drug design are crucial. Cloud computing and general purpose graphics processing unit (GPGPU) computing have been used in virtual screening and molecular dynamics simulations. Not surprisingly, there is a growing demand for computer systems which combine these resources. In the present review, we summarize and discuss these various topics of drug design. PMID:27075578

Implementation of a generic SFC-MS method for the quality control of potentially counterfeited medicinal cannabis with synthetic cannabinoids.

PubMed

Jambo, Hugues; Dispas, Amandine; Avohou, Hermane T; André, Sébastien; Hubert, Cédric; Lebrun, Pierre; Ziemons, Éric; Hubert, Philippe

2018-06-05

In this study, we describe the development of a SFC-MS method for the quality control of cannabis plants that could be potentially adulterated with synthetic cannabinoids. Considering the high number of already available synthetic cannabinoids and the high rate of development of novel structures, we aimed to develop a generic method suitable for the analysis of a large panel of substances using seventeen synthetic cannabinoids from multiple classes as model compounds. Firstly, a suitable column was chosen after a screening phase. Secondly, optimal operating conditions were obtained following a robust optimization strategy based on a design of experiments and design space methodology (DoE-DS). Finally, the quantitative performances of the method were assessed with a validation according to the total error approach. The developed method has a run time of 9.4 min. It uses a simple modifier composition of methanol with 2% H 2 O and requires minimal sample preparation. It can chromatographically separate natural cannabinoids (except THC-A and CBD-A) from the synthetics assessed. Also, the use of mass spectrometry provides sensitivity and specificity. Moreover, this quality by design (QbD) approach permits the tuning of the method (within the DS) during routine analysis to achieve a desirable separation since the future compounds that should be analyzed could be unknown. The method was validated for the quantitation of a selected synthetic cannabinoid in fiber-type cannabis matrix over the range of 2.5% - 7.5% (w/w) with LOD value as low as 14.4 ng/mL. This generic method should be easy to implement in customs or QC laboratories in the context of counterfeit drugs tracking. Copyright © 2018 Elsevier B.V. All rights reserved.

Impact of synthetic canine cerumen on in vitro penetration of auricular skin of dogs by florfenicol, terbinafine, and betamethasone acetate.

PubMed

Ehling, Sarah; Baynes, Ronald E; Bäumer, Wolfgang

2018-03-01

OBJECTIVE To determine the pharmacokinetics of florfenicol, terbinafine, and betamethasone acetate after topical application to canine auricular skin and the influence of synthetic canine cerumen on pharmacokinetics. SAMPLE Auricular skin from 6 euthanized shelter dogs (3 females and 3 neutered males with no visible signs of otitis externa). PROCEDURES Skin adjacent to the external opening of the ear canal was collected and prepared for use in a 2-compartment flow-through diffusion cell system to evaluate penetration of an otic gel containing florfenicol, terbinafine, and betamethasone acetate over a 24-hour period. Radiolabeled 14 C-terbinafine hydrochloride and 3 H-betamethasone acetate were added to the gel to determine dermal penetration and distribution. Florfenicol absorption was determined by use of high-performance liquid chromatography-UV detection. Additionally, the effect of synthetic canine cerumen on the pharmacokinetics of all compounds was evaluated. RESULTS During the 24-hour experiment, mean ± SD percentage absorption without the presence of synthetic canine cerumen was 0.28 ± 0.09% for 3H-betamethasone acetate, 0.06 ± 0.06% for florfenicol, and 0.06 ± 0.02% for 14C-terbinafine hydrochloride. Absorption profiles revealed no impact of synthetic canine cerumen on skin absorption for all 3 active compounds in the gel or on skin distribution of 3 H-betamethasone acetate and 14 C-terbinafine hydrochloride. CONCLUSIONS AND CLINICAL RELEVANCE 3 H-betamethasone acetate, 14 C-terbinafine hydrochloride, and florfenicol were all absorbed in vitro through healthy auricular skin specimens within the first 24 hours after topical application. Synthetic canine cerumen had no impact on dermal absorption in vitro, but it may serve as a temporary reservoir that prolongs the release of topical drugs.

Obama Kennedy Space Center Visit

NASA Image and Video Library

2010-04-14

President Barack Obama tours the commercial rocket processing facility of Space Exploration Technologies, known as SpaceX, along with Elon Musk, SpaceX CEO at Cape Canaveral Air Force Station, Cape Canaveral, Fla. on Thursday, April 15, 2010. Obama also visited the NASA Kennedy Space Center to deliver remarks on the bold new course the administration is charting to maintain U.S. leadership in human space flight. Photo Credit: (NASA/Bill Ingalls)

Exploiting The New Commercial Space Race

DTIC Science & Technology

2016-02-10

developing orbital launch vehicle.  PayPal founder and Tesla Motors CEO Elon Musk’s SpaceX which is developing space access technologies.  Microsoft co...Resources company is developing asteroid mining technology Among the upstart companies, SpaceX has emerged as the leading contender to traditional...US commercial space companies. SpaceX was founded in 2002 by South African billionaire Elon Musk, with the ultimate goal of enabling people to live

40 CFR 60.708 - Delegation of authority.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor Processes § 60.708...

40 CFR 60.708 - Delegation of authority.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES Standards of Performance for Volatile Organic Compound Emissions From Synthetic Organic Chemical Manufacturing Industry (SOCMI) Reactor Processes § 60.708...

Integration of Fermentation and Organic Synthesis: Studies of Roquefortine C and Biosynthetic Derivatives

NASA Astrophysics Data System (ADS)

Gober, Claire Marie

Roquefortine C is one of the most ubiquitous indoline alkaloids of fungal origin. It has been isolated from over 30 different species of Penicillium fungi and has garnered attention in recent years for its role as a biosynthetic precursor to the triazaspirocyclic natural products glandicoline B, meleagrin, and oxaline. The triazaspirocyclic motif, which encompasses three nitrogen atoms attached to one quaternary carbon forming a spirocyclic scaffold, is a unique chemical moiety that has been shown to impart a wide array of biological activity, from anti-bacterial activity and antiproliferative activity against cancer cell lines to anti-biofouling against marine organisms. Despite the promise of these compounds in the pharmaceutical and materials industries, few syntheses of triazaspirocycles exist in the literature. The biosynthesis of roquefortine C-derived triazaspirocycles, however, provides inspiration for the synthesis of these compounds, namely through a nitrone-promoted transannular rearrangement. This type of internal rearrangement has never been carried out synthetically and would provide an efficient stereoselective synthesis of triazaspirocycles. This work encompasses efforts towards elucidating the biosynthetic pathway of roquefortine C-derived triazaspirocycles as well as synthetic efforts towards the construction of triazaspirocycles. Chapter 1 will discuss a large-scale fermentation procedure for the production of roquefortine C from Penicillium crustosum. Chapters 2 and 3 explore (through enzymatic and synthetic means, respectively) the formation of the key indoline nitrone moiety required for the proposed transannular rearrangement. Finally, chapter 4 will discuss synthetic efforts towards the synthesis of triazaspirocycles. This work has considerably enhanced our understanding of the roquefortine C biosynthetic pathway and the unique chemistry of this natural product, and our efforts towards the synthesis of triazaspirocycles will facilitate the use of these compounds in numerous applications.

Co-Compartmentation of Terpene Biosynthesis and Storage via Synthetic Droplet.

PubMed

Zhao, Cheng; Kim, YongKyoung; Zeng, Yining; Li, Man; Wang, Xin; Hu, Cheng; Gorman, Connor; Dai, Susie Y; Ding, Shi-You; Yuan, Joshua S

2018-03-16

Traditional bioproduct engineering focuses on pathway optimization, yet is often complicated by product inhibition, downstream consumption, and the toxicity of certain products. Here, we present the co-compartmentation of biosynthesis and storage via a synthetic droplet as an effective new strategy to improve the bioproduct yield, with squalene as a model compound. A hydrophobic protein was designed and introduced into the tobacco chloroplast to generate a synthetic droplet for terpene storage. Simultaneously, squalene biosynthesis enzymes were introduced to chloroplasts together with the droplet-forming protein to co-compartmentalize the biosynthesis and storage of squalene. The strategy has enabled a record yield of squalene at 2.6 mg/g fresh weight without compromising plant growth. Confocal fluorescent microscopy imaging, stimulated Raman scattering microscopy, and droplet composition analysis confirmed the formation of synthetic storage droplet in chloroplast. The co-compartmentation of synthetic storage droplet with a targeted metabolic pathway engineering represents a new strategy for enhancing bioproduct yield.

Fluorescence spectroscopy as a specific tool for the interaction study of two surfactants with natural and synthetic organic compounds

NASA Astrophysics Data System (ADS)

Jung, Aude-Valérie; Frochot, Céline; Bersillon, Jean-Luc

2016-04-01

Four different techniques were used to study the binding of cationic cetyltrimethylammonium bromide (CTAB) and non-ionic nonylphenylethoxyl (NPE) surfactants to three synthetic organic components that mimic humic-like aggregates and to two natural aggregated humic substances (HS) extracted from aquatic suspended matter. The composition of synthetic organic components were chosen to be similar to high molecular weight highly processed terrigenous HS and low and high molecular weight less processed terrigenous (or aquatic terrigenous) HS. The natural HS were extracted under two different meteorological conditions (rainy and dry periods). No significant interaction between the non-ionic surfactant and any of the studied compounds was found. Concerning CTAB; pH, conductivity and turbidity measurements, along with fluorescence spectroscopy were combined to provide a better understanding of interactions between organic aggregates and the surfactant. The spectroscopic data show that a "highly processed terrigenous HS" fluorophore interacts in a different way with the cationic surfactant than an "aquatic terrigenous (or less processed terrigenous) HS" fluorophore does. Under similar conditions, some spectral changes in the fluorescence signal are correlated to changes in non-specific physical-chemical parameters (pH, turbidity, conductivity) for the organic compounds tested. The complexation mechanism is essentially governed by charge neutralization, which can be monitored specifically by the fluorescence of the organic moieties.

A semi-synthetic natural product blocks collagen induced arthritis by preferentially suppressing the production of IL-6.

PubMed

Kulkarni-Almeida, Asha; Shah, Meet; Jadhav, Mahesh; Hegde, Bindu; Trivedi, Jacqueline; Mishra, Prabhu D; Mahajan, Girish B; Dadarkar, Shruta; Gupte, Ravindra; Dagia, Nilesh

2016-04-01

Rheumatoid arthritis (RA), an autoimmune-inflammatory disease is characterized by dysregulation of signal transduction pathways, increased production of pro-inflammatory cytokines, enhanced leukocyte infiltration into synovial microvascular endothelium, extensive formation of hyper proliferative pannus, degradation of cartilage and bone erosion. Several compounds that abrogate cytokine production demonstrate a therapeutic effect in experimental models of arthritis. In this study, we report that a novel semi-synthetic natural product (Compound A) being a preferential IL-6 inhibitor, is efficacious in a murine model of arthritis. In vitro evaluations of pro-inflammatory cytokine production reveal that Compound A preferentially inhibits induced production of IL-6 and not TNF-α from THP-1 cells and isolated human monocytes. Furthermore, Compound A robustly inhibits the spontaneous production of IL-6 from pathologically relevant synovial tissue cells isolated from patients with active RA. In a physiologically relevant assay, Compound A selectively inhibits the activated T cell contact-mediated production of IL-6 from human monocytes. Compound A, at pharmacologically efficacious concentrations, does not significantly curtail the LPS-induced activation of p38 MAPKs. In the collagen-induced arthritis (CIA) mouse model (i) macroscopic observations demonstrate that Compound A, administered subcutaneously in a therapeutic regimen, significantly and dose-dependently inhibits disease associated increases in articular index and paw thickness; (ii) histological analyses of paw tissues reveal that Compound A prominently diminishes joint destruction, hyperproliferative pannus formation and infiltration of inflammatory cells. Collectively, these results provide direct evidence that Compound A, a novel preferential IL-6 inhibitor, suppresses collagen-induced arthritis, and may be a potential therapeutic for treating patients with active RA. Copyright © 2016. Published by Elsevier B.V.

Prenatal toxicity of synthetic amorphous silica nanomaterial in rats.

PubMed

Hofmann, Thomas; Schneider, Steffen; Wolterbeek, André; van de Sandt, Han; Landsiedel, Robert; van Ravenzwaay, Bennard

2015-08-15

Synthetic amorphous silica is a nanostructured material, which is produced and used in a wide variety of technological applications and consumer products. No regulatory prenatal toxicity studies with this substance were reported yet. Therefore, synthetic amorphous silica was tested for prenatal toxicity, according to OECD guideline 414 in Wistar rats following oral (gavage) administration at the dose levels 0, 100, 300, or 1000mg/kg bw/d from gestation day 6-19. At gestation day 20, all pregnant animals were examined by cesarean section. Numbers of corpora lutea, implantations, resorptions, live and dead fetuses were counted. Fetal and placental weights were determined. Fetuses were examined for external, visceral and skeletal abnormalities. No maternal toxicity was observed at any dose level. Likewise, administration of the test compound did not alter cesarean section parameters and did not influence fetal or placental weights. No compound-related increase in the incidence of malformations or variations was observed in the fetuses. The no observed adverse effect level (NOAEL) was 1000mg/kg bw/d. Copyright © 2015 Elsevier Inc. All rights reserved.

Prevention of non-enzymatic glycosylation (glycation): Implication in the treatment of diabetic complication

PubMed Central

Younus, H.; Anwar, S.

2016-01-01

Non-enzymatic glycosylation (glycation) plays an important role in the development of physiological and pathophysiological processes such as aging, diabetes, atherosclerosis, neurodegenerative diseases and chronic renal failure. Preventing glycation can minimize diabetic complications. Glycation can be prevented by the natural defence system in the body, synthetic inhibitors and natural inhibitors. Synthetic inhibitors may prevent glycation through several possible mechanisms. They might inhibit the glycation by interfering with the attachment of sugars with proteins, by inhibiting the late stage of glycation or by preventing Amadori product formation. Furthermore, their ability to scavenge free radicals and to break cross-links might be other mechanisms responsible for their potential to inhibit glycation. Naturally occurring phytochemicals/products have been found to be relatively non-toxic as compared to synthetic compounds, and are inexpensive and available in an ingestible form. A large number of plants and natural biomolecules have been shown to have antidiabetic effects. Several hypoglycaemic compounds have anti-oxidant properties. The present review describes the various ways in which glycation can be prevented. PMID:27103908

Conversion of sugars present in rice hull hydrolysates into ethanol by Spathaspora arborariae, Saccharomyces cerevisiae, and their co-fermentations.

PubMed

da Cunha-Pereira, Fernanda; Hickert, Lilian Raquel; Sehnem, Nicole Teixeira; de Souza-Cruz, Priscila Brasil; Rosa, Carlos Augusto; Ayub, Marco Antônio Záchia

2011-03-01

The production of ethanol by the new yeast Spathaspora arborariae using rice hull hydrolysate (RHH) as substrate, either alone or in co-cultures with Saccharomyces cerevisiae is presented. Cultivations were also carried out in synthetic medium to gather physiological information on these systems, especially concerning their ability to grow and produce ethanol in the presence of acetic acid, furfural, and hydroxymethylfurfural, which are toxic compounds usually present in lignocellulosic hydrolysates. S. arborariae was able to metabolize xilose and glucose present in the hydrolysate, with ethanol yields (Y(P/S)(et)) of 0.45. In co-cultures, ethanol yields peaked to 0.77 and 0.62 in the synthetic medium and in RHH, respectively. When the toxic compounds were added to the synthetic medium, their presence produced negative effects on biomass formation and ethanol productivity. This work shows good prospects for the use of the new yeast S. arborariae alone and in co-cultures with S. cerevisiae for ethanol production. Copyright © 2010 Elsevier Ltd. All rights reserved.

USN/USMC Commander’s Quick Reference Legal Handbook

DTIC Science & Technology

2015-01-01

compounds of designer drugs. [See references (a), (f), and (g).] Commanders shall obtain authorization for testing for synthetic drug compounds from...17 Pre-Trial Agreements 19 Post -Trial Review 21 Victim/Witness Issues 23 Section II: Administrative...advocate except in extraordinary circumstances.  Only flag or general officers (and a very few specifically designated non-flag/general officers who are

Spatial variability of volatile organic compounds in streams on Long Island, New York, and in New Jersey

USGS Publications Warehouse

O'Brien, Anne K.; Reiser, Robert G.; Gylling, Helle

1997-01-01

Volatile organic compounds (VOCs) are found in almost all natural and synthetic materials and are commonly used in fuels, fuel additives, solvents, perfumes, flavor additives, and deodorants. Potential health hazards and environmental degradation resulting from the widespread use of VOCs has prompted increasing concern among scientists, industry, and the general public.

The potential for prebiotic synthesis in hydrothermal systems. [Abstract only

NASA Technical Reports Server (NTRS)

Ferris, James P.

1994-01-01

Contemporary hydrothermal systems provide a reducing environment where organic compounds are formed and may react to generate the molecules used in the first living systems. The organic compounds percolate through mineral assemblages at a variety of temperatures so the proposed synthetic reactions are driven by heat and catalyzed by minerals (Ferris, 1992). Some examples of potential prebiotic reactions are discussed.

Reconnaissance-Level Assessment of Water Quality Near Flandreau, South Dakota

DTIC Science & Technology

2002-01-01

associations with adverse health effects have been established. Con- centrations of some selected analytes were less than U.S. Environmental ...unregulated synthetic organic compounds in aquatic environments . This study provides information concerning the occurrence of selected organic compounds...water sites. Selected data from various other investigations also are described. A total of 15 environmental samples, which included two sets of

The synthesis of monomers with pendent ethynyl groups for modified high performance thermoplastics

NASA Technical Reports Server (NTRS)

Nwokogu, Godson C.; Antoine, Miquel D.; Ansong, Omari

1994-01-01

Synthetic schemes were developed and optimized for twelve new monomers possessing unique structural features and one aspartimide. Two synthetic pathways were compared for preparation of the triarylethane monomers with pendent ethynyl groups. The results show that one of these pathways can be generally applied. The alternative pathway was applicable to the preparation of only one of the twelve compounds, the problem being secondary reactions of the initially formed desired product.

Exploiting the acylating nature of the imide-Ugi intermediate: a straightforward synthesis of tetrahydro-1,4-benzodiazepin-2-ones.

PubMed

Mossetti, Riccardo; Saggiorato, Dèsirèe; Tron, Gian Cesare

2011-12-16

We describe a simple and novel protocol for the synthesis of tetrahydro-1,4-benzodiazepin-2-ones with three points of diversity, exploiting the acylating properties of the recently rediscovered Ugi-imide. The final compounds can be easily prepared in three synthetic steps using a multicomponent reaction, a Staudinger reduction, and an acylative protocol, with good to excellent yields for each synthetic step.

Perchlorate and Halogen-Free High Energy Dense Oxidizers (HEDO)

DTIC Science & Technology

2011-06-01

nitric acid indicate that the covalent oxalic acid dinitrate ester should be more stable than the ionic dinitronium oxalate . The following three...synthetic strategies were developed to generate compound 11 (Scheme 17). Strategy I is the nitration of anhydrous oxalic acid with nitric acid (100...temperatures (25 to –30 °C) and in all dry solvents used. Scheme 17: Synthetic strategies for the production of oxalic acid dinitrate ester (11