text:
Volume 17, January
Volume 17, November
Marine Drugs
Submit to Marine Drugs Review for Marine Drugs
Marine Drugs Home
volume 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1
issue 1 2 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1
Mar. Drugs, Volume 17, Issue 12 (December 2019) – 62 articles
Cover Story (view full-size image) Meroterpenes, prenylated quinones/hydroquinones commonly found in marine organisms, stand out for [...] Read more. Meroterpenes, prenylated quinones/hydroquinones commonly found in marine organisms, stand out for their potential as anticancer agents. SAR studies on both natural and synthetic meroterpenes with linear isoprenoid chains linked at quinone ring evidenced that their bioactivity is strongly affected by the nature and position of the quinone substituents and by the prenyl group length. On this basis, we synthesized several quinones and thiazinoquinones inspired to the pro-apoptotic natural geranylthiazinoquinone aplidinone A, isolated from the marine ascidian A. conicum. The effect of these molecules on viability and proliferation of different human cancer cells was investigated; one of the tested compounds exerted significant antiproliferative activity and a cytostatic effect referable to a G0/G1 cell-cycle arrest in BxPC-3 cells after 24 h treatment. View this paper.
Bioactive Secondary Metabolites from the Culture of the Mangrove-Derived Fungus Daldinia eschscholtzii HJ004
by Hai-Xia Liao , Tai-Ming Shao , Rong-Qing Mei , Guo-Lei Huang , Xue-Ming Zhou , Cai-Juan Zheng and Chang-Yun Wang
Mar. Drugs 2019, 17(12), 710; https://doi.org/10.3390/md17120710 - 17 Dec 2019
Two new polyketides, 8-O-methylnodulisporin F (1) and nodulisporin H (2), two new naphthoquinones, 5-hydroxy-2-methoxy-6,7-dimethyl-1,4-naphthoquinone (3) and 5-hydroxy-2-methoxynaphtho[9–c]furan-1,4-dione (4), and a new naphthofuran 1,3,8-trimethoxynaphtho[9–c]furan (5), along with five [...] Read more.
Two new polyketides, 8-O-methylnodulisporin F (1) and nodulisporin H (2), two new naphthoquinones, 5-hydroxy-2-methoxy-6,7-dimethyl-1,4-naphthoquinone (3) and 5-hydroxy-2-methoxynaphtho[9–c]furan-1,4-dione (4), and a new naphthofuran 1,3,8-trimethoxynaphtho[9–c]furan (5), along with five known compounds 4-O-methyl eleutherol (6), 2-acetyl-7-methoxybenzofuran (7), (-)-orthosporin (8), diaporthin (9), and 6-hydroxymellein (10), were obtained from the EtOAc extract of the mangrove-derived fungus Daldinia eschscholtzii HJ004. The structures of the isolated compounds were elucidated by extensive NMR and MS analyses, while the absolute configurations of the stereogenic carbons were established based on experimental and calculated electronic circular dichroism spectra. Compounds 4 and 7 displayed a potent inhibitory activity against α-glucosidase with the IC50 values of 5.7 and 1.1 μg/mL, respectively. Compounds 1 and 2 showed a moderate antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA) and Bacillus cereus, with minimum inhibitory concentration (MIC) values ranging from 6.25 to 12.5 μg/mL. Compound 3 exhibited antibacterial activity against B. cereus with the MIC value of 12.5 μg/mL. Full article
Siderophore (from Synechococcus sp. PCC 7002)-Chelated Iron Promotes Iron Uptake in Caco-2 Cells and Ameliorates Iron Deficiency in Rats
by Xue Feng , Suisui Jiang , Fan Zhang , Runfang Wang , Yuanhui Zhao and Mingyong Zeng
Siderophores are iron chelators with low molecular weight secreted by microorganisms. Siderophores have the potential to become natural iron fortifiers. To explore the feasibility of the application of Synechococcus sp. PCC7002-derived siderophores as iron fortifiers, Synechococcus sp. PCC7002, as a carrier, was fermented [...] Read more.
Siderophores are iron chelators with low molecular weight secreted by microorganisms. Siderophores have the potential to become natural iron fortifiers. To explore the feasibility of the application of Synechococcus sp. PCC7002-derived siderophores as iron fortifiers, Synechococcus sp. PCC7002, as a carrier, was fermented to produce siderophores. The absorption mechanism and anemia intervention effect of siderophores-chelated iron (SCI) were studied through the polarized Caco-2 Cell monolayers and the rat model of iron-deficiency anemia, respectively. The results indicated that siderophores (from Synechococcus sp. PCC7002) had an enhancing effect on iron absorption in polarized Caco-2 cell monolayers. The main absorption site of SCI was duodenum with pH 5.5, and the absorption methods included endocytosis and DMT1, with endocytosis being dominant. The effect of sodium phytate on SCI was less than that of ferrous sulfate. Therefore, SCI could resist inhibitory iron absorption factors in polarized Caco-2 cell monolayers. SCI showed significantly higher relative bioavailability (133.58 ± 15.42%) than ferrous sulfate (100 ± 14.84%) and ferric citrate (66.34 ± 8.715%) in the rat model. Food intake, hemoglobin concentration, and hematocrit and serum iron concentration of rats improved significantly after Fe-repletion. Overall, this study indicated that siderophores derived from Synechococcus sp. PCC7002 could be an effective and feasible iron nutritive fortifier. Full article
Pepsin-Soluble Collagen from the Skin of Lophius litulo: A Preliminary Study Evaluating Physicochemical, Antioxidant, and Wound Healing Properties
by Wen Zhang , Jiawen Zheng , Xiaoxiao Tian , Yunping Tang , Guofang Ding , Zuisu Yang and Huoxi Jin
The structure of pepsin-solubilized collagen (PSC) obtained from the skin of Lophius litulon was analyzed using the sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). SDS-PAGE results showed that PSC from Lophius litulon skin was [...] Read more.
The structure of pepsin-solubilized collagen (PSC) obtained from the skin of Lophius litulon was analyzed using the sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). SDS-PAGE results showed that PSC from Lophius litulon skin was collagen type I and had collagen-specific α1, α2, β, and γ chains. FTIR results indicated that the infrared spectrum of PSC ranged from 400 to 4000 cm−1, with five main amide bands. SEM revealed the microstructure of PSC, which consisted of clear fibrous and porous structures. In vitro antioxidant studies demonstrated that PSC revealed the scavenging ability for 2,2-diphenyl-1-picrylhydrazyl (DPPH), HO·, O2−·, and ABTS·. Moreover, animal experiments were conducted to evaluate the biocompatibility of PSC. The collagen sponge group showed a good biocompatibility in the skin wound model and may play a positive role in the progression of the healing process. The cumulative results suggest that collagen from the skin of Lophius litulon has potential applications in wound healing due to its good biocompatibility. Full article
(This article belongs to the Special Issue Marine Skeletal Biopolymers and Proteins, and Their Biomedical Application)
Supplementary File 1 (PDF, 43192 KB)
Plakinamine P, A Steroidal Alkaloid with Bactericidal Activity against Mycobacterium tuberculosis
by Carolina Rodrigues Felix , Jill C. Roberts , Priscilla L. Winder , Rashmi Gupta , M. Cristina Diaz , Shirley A. Pomponi , Amy E. Wright and Kyle H. Rohde
Tuberculosis is the leading cause of death due to infectious disease worldwide. There is an urgent need for more effective compounds against this pathogen to control the disease. Investigation of the anti-mycobacterial activity of a deep-water sponge of the genus Plakina revealed the [...] Read more.
Tuberculosis is the leading cause of death due to infectious disease worldwide. There is an urgent need for more effective compounds against this pathogen to control the disease. Investigation of the anti-mycobacterial activity of a deep-water sponge of the genus Plakina revealed the presence of a new steroidal alkaloid of the plakinamine class, which we have given the common name plakinamine P. Its structure is most similar to plakinamine L, which also has an acyclic side chain. Careful dissection of the nuclear magnetic resonance data, collected in multiple solvents, suggests that the dimethyl amino group at the 3 position is in an equatorial rather than axial position unlike previously reported plakinamines. Plakinamine P was bactericidal against M. tuberculosis, and exhibited moderate activity against other mycobacterial pathogens, such as M. abscessus and M. avium. Furthermore, it had low toxicity against J774 macrophages, yielding a selectivity index (SI, or IC50/MIC) of 8.4. In conclusion, this work provides a promising scaffold to the tuberculosis drug discovery pipeline. Future work to determine the molecular target of this compound may reveal a pathway essential for M. tuberculosis survival during infection. Full article
Fragilides U–W: New 11,20-Epoxybriaranes from the Sea Whip Gorgonian Coral Junceella fragilis
by Tung-Pin Su , Chien-Han Yuan , Yi-Ming Jhu , Bo-Rong Peng , Zhi-Hong Wen , Yu-Jen Wu , Tung-Ying Wu , Hong-Wen Liu and Ping-Jyun Sung
Three new 11,20-epoxybriaranes—fragilides U–W (1–3), as well as two known metabolites, junceellonoid D (4) and junceellin (5), were obtained from the octocoral Junceella fragilis. The structures of briaranes 1–3 were elucidated by [...] Read more.
Three new 11,20-epoxybriaranes—fragilides U–W (1–3), as well as two known metabolites, junceellonoid D (4) and junceellin (5), were obtained from the octocoral Junceella fragilis. The structures of briaranes 1–3 were elucidated by spectroscopic methods and briaranes 3 and 5 displayed inhibition effects on inducible nitric oxide synthase (iNOS) release from RAW264.7. Full article
(This article belongs to the Special Issue Bioactive Compounds from Coral Reef Organisms)
Characterization of Carotenoid Biosynthesis in Newly Isolated Deinococcus sp. AJ005 and Investigation of the Effects of Environmental Conditions on Cell Growth and Carotenoid Biosynthesis
by Jun Young Choi , Kunjoong Lee and Pyung Cheon Lee
Our purpose was to characterize the structures of deinoxanthin from Deinococcus sp. AJ005. The latter is a novel reddish strain and was found to synthesize two main acyclic carotenoids: deinoxanthin and its derivative. The derivative (2-keto-deinoxanthin) contains a 2-keto functional group instead of [...] Read more.
Our purpose was to characterize the structures of deinoxanthin from Deinococcus sp. AJ005. The latter is a novel reddish strain and was found to synthesize two main acyclic carotenoids: deinoxanthin and its derivative. The derivative (2-keto-deinoxanthin) contains a 2-keto functional group instead of a 2-hydroxyl group on a β-ionone ring. A deinoxanthin biosynthesis pathway of Deinococcus sp. AJ005 involving eight putative enzymes was proposed according to genome annotation analysis and chemical identification of deinoxanthin. Optimal culture pH and temperature for Deinococcus sp. AJ005 growth were pH 7.4 and 20 °C. Sucrose as a carbon source significantly enhanced the cell growth in comparison with glucose, glycerol, maltose, lactose, and galactose. When batch fermentation was performed in a bioreactor containing 40g/L sucrose, total carotenoid production was 650% higher than that in a medium without sucrose supplementation. The culture conditions found in this study should provide the basis for the development of fermentation strategies for the production of deinoxanthin and of its derivative by means of Deinococcus sp. AJ005. Full article
(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments)
Stable Tetrodotoxin Production by Bacillus sp. Strain 1839
by Daria I. Melnikova , Anna E. Vlasenko and Timur Yu. Magarlamov
For the first time, tetrodotoxin (TTX) was detected in a bacterial strain after five years of cultivation in laboratory conditions since its isolation from the animal host. A reliable method suitable for bacterial samples, high-performance liquid chromatography with tandem mass spectrometry, was used [...] Read more.
For the first time, tetrodotoxin (TTX) was detected in a bacterial strain after five years of cultivation in laboratory conditions since its isolation from the animal host. A reliable method suitable for bacterial samples, high-performance liquid chromatography with tandem mass spectrometry, was used for toxin detection in spore and vegetative cultures of Bacillus sp. 1839. TTX was detected in a spore culture of the strain. Full article
(This article belongs to the Special Issue Tetrodotoxin: Chemistry, Toxicity, Source, Distribution and Detection)
Isolation, Optimization of Fermentation Conditions, and Characterization of an Exopolysaccharide from Pseudoalteromonas agarivorans Hao 2018
by Lujiang Hao , Wenlin Liu , Kai Liu , Kai Shan , Chunlei Wang , Chenxiang Xi , Jianbang Liu , Qiuping Fan , Xiaofei Zhang , Xiaoping Lu , Yanrui Xu , RuiWen Cao , Yaohong Ma , Lan Zheng and Bo Cui
In recent years, the wide application of exopolysaccharides (EPSs) in food, cosmetics, medicine, and other fields has drawn tremendous attention. In this study, an EPS produced by Pseudoalteromonas agarivorans Hao 2018 was isolated and purified, and its fermentation conditions were optimized. Its structure [...] Read more.
In recent years, the wide application of exopolysaccharides (EPSs) in food, cosmetics, medicine, and other fields has drawn tremendous attention. In this study, an EPS produced by Pseudoalteromonas agarivorans Hao 2018 was isolated and purified, and its fermentation conditions were optimized. Its structure and biological functions were also studied. The purity and molecular weight of EPS were determined by high performance liquid chromatography (HPLC), and the EPS exhibited a number average of 2.26 × 105 and a weight average of 2.84 × 105. EPS has good adsorption for Cu2+ and Pb2+. The adsorption rates can reach up to 69.79% and 82.46%, respectively. The hygroscopic property of EPS was higher than that of chitosan, but slightly lower than that of sodium hyaluronate. However, the water-retaining activity of EPS was similar to that of chitosan and sodium hyaluronate. EPS has strong ability to scavenge free radicals, including OH radical and O2− radical. Further, its activity on O2− radicals has similarities with that of vitamin C. EPS has broad application prospects in many fields, such as cosmetics, environmental protection. Full article
Fucoxanthin Alleviates Oxidative Stress through Akt/Sirt1/FoxO3α Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs
by Guanyu Yang , Lin Jin , Dongxiao Zheng , Xiaoliang Tang , Junwei Yang , Lingxuan Fan and Xi Xie
As one of the main marine carotenoids, fucoxanthin has strong antioxidant activity. FoxO3α, a member of the forkhead box O family of transcription factors, plays an important role in DN by regulating oxidative stress. The activity of FoxO3α is related to its phosphorylation [...] Read more.
As one of the main marine carotenoids, fucoxanthin has strong antioxidant activity. FoxO3α, a member of the forkhead box O family of transcription factors, plays an important role in DN by regulating oxidative stress. The activity of FoxO3α is related to its phosphorylation and acetylation status, regulated by Akt and Sirt1, a lysine deacetylase. Our study aimed to investigate whether fucoxanthin could alleviate oxidative stress and fibrosis via FoxO3α in DN and whether Akt and Sirt1 were involved. We found that in GMCs cultured in HG, fucoxanthin treatment significantly reduced the expression of FN and collagen IV, as well as reactive oxygen species generation, suggesting that fucoxanthin is beneficial to alleviate both fibrosis and oxidative stress in DN. In addition, we found that fucoxanthin decreased the phosphorylation and acetylation level of FoxO3α, reversed the protein level of FoxO3α inhibited by HG, and then promoted the nuclear transport of FoxO3α. Besides, fucoxanthin promoted the expression of manganese superoxide dismutase, a downstream target of FoxO3α. Furthermore, we found that fucoxanthin reversed the activation of Akt and inhibition of Sirt1. However, the enhancement of fucoxanthin in FoxO3α expression and nuclear transport was significantly decreased by pretreatment with Akt activator SC79 or Sirt1 inhibitor EX527. In summary, our study explored fucoxanthin alleviated oxidative stress and fibrosis induced by HG through Akt/Sirt1/FoxO3α signaling in GMCs, suggesting fucoxanthin is a potential therapeutic strategy for DN. Full article
Supplementary File 1 (JPG, 365 KB)
A Versatile and Robust Serine Protease Inhibitor Scaffold from Actinia tenebrosa
by Xingchen Chen , Darren Leahy , Jessica Van Haeften , Perry Hartfield , Peter J. Prentis , Chloé A. van der Burg , Joachim M. Surm , Ana Pavasovic , Bruno Madio , Brett R. Hamilton , Glenn F. King , Eivind A. B. Undheim , Maria Brattsand and Jonathan M. Harris
Serine proteases play pivotal roles in normal physiology and a spectrum of patho-physiological processes. Accordingly, there is considerable interest in the discovery and design of potent serine protease inhibitors for therapeutic applications. This led to concerted efforts to discover versatile and robust molecular [...] Read more.
Serine proteases play pivotal roles in normal physiology and a spectrum of patho-physiological processes. Accordingly, there is considerable interest in the discovery and design of potent serine protease inhibitors for therapeutic applications. This led to concerted efforts to discover versatile and robust molecular scaffolds for inhibitor design. This investigation is a bioprospecting study that aims to isolate and identify protease inhibitors from the cnidarian Actinia tenebrosa. The study isolated two Kunitz-type protease inhibitors with very similar sequences but quite divergent inhibitory potencies when assayed against bovine trypsin, chymostrypsin, and a selection of human sequence-related peptidases. Homology modeling and molecular dynamics simulations of these inhibitors in complex with their targets were carried out and, collectively, these methodologies enabled the definition of a versatile scaffold for inhibitor design. Thermal denaturation studies showed that the inhibitors were remarkably robust. To gain a fine-grained map of the residues responsible for this stability, we conducted in silico alanine scanning and quantified individual residue contributions to the inhibitor's stability. Sequences of these inhibitors were then used to search for Kunitz homologs in an A. tenebrosa transcriptome library, resulting in the discovery of a further 14 related sequences. Consensus analysis of these variants identified a rich molecular diversity of Kunitz domains and expanded the palette of potential residue substitutions for rational inhibitor design using this domain. Full article
(This article belongs to the Special Issue Anthozoan Toxins: Using New Approaches to Understand Their Composition, Distribution, and Function)
Genome-Wide Identification and Characterization of SODs in Zhikong Scallop Reveals Gene Expansion and Regulation Divergence after Toxic Dinoflagellate Exposure
by Shanshan Lian , Liang Zhao , Xiaogang Xun , Jiarun Lou , Moli Li , Xu Li , Shi Wang , Lingling Zhang , Xiaoli Hu and Zhenmin Bao
As filter-feeding animals mainly ingesting microalgae, bivalves could accumulate paralytic shellfish toxins (PSTs) produced by harmful algae through diet. To protect themselves from the toxic effects of PSTs, especially the concomitant oxidative damage, the production of superoxide dismutase (SOD), which is the only [...] Read more.
As filter-feeding animals mainly ingesting microalgae, bivalves could accumulate paralytic shellfish toxins (PSTs) produced by harmful algae through diet. To protect themselves from the toxic effects of PSTs, especially the concomitant oxidative damage, the production of superoxide dismutase (SOD), which is the only eukaryotic metalloenzyme capable of detoxifying superoxide, may assist with toxin tolerance in bivalves. To better understand this process, in the present study, we performed the first systematic analysis of SOD genes in bivalve Chlamys farreri, an important aquaculture species in China. A total of six Cu/Zn-SODs (SOD1-6) and two Mn-SODs (SOD7, SOD8) were identified in C. farreri, with gene expansion being revealed in Cu/Zn-SODs. In scallops exposed to two different PSTs-producing dinoflagellates, Alexandrium minutum and A. catenella, expression regulation of SOD genes was analyzed in the top ranked toxin-rich organs, the hepatopancreas and the kidney. In hepatopancreas, which mainly accumulates the incoming PSTs, all of the six Cu/Zn-SODs showed significant alterations after A. minutum exposure, with SOD1, 2, 3, 5, and 6 being up-regulated, and SOD4 being down-regulated, while no significant change was detected in Mn-SODs. After A. catenella exposure, up-regulation was observed in SOD2, 4, 6, and 8, and SOD7 was down-regulated. In the kidney, where PSTs transformation occurs, SOD4, 5, 6, and 8 were up-regulated, and SOD7 was down-regulated in response to A. minutum feeding. After A. catenella exposure, all the Cu/Zn-SODs except SOD1 were up-regulated, and SOD7 was down-regulated in kidney. Overall, in scallops after ingesting different toxic algae, SOD up-regulation mainly occurred in the expanded Cu/Zn-SOD group, and SOD6 was the only member being up-regulated in both toxic organs, which also showed the highest fold change among all the SODs, implying the importance of SOD6 in protecting scallops from the stress of PSTs. Our results suggest the diverse function of scallop SODs in response to the PST-producing algae challenge, and the expansion of Cu/Zn-SODs might be implicated in the adaptive evolution of scallops or bivalves with respect to antioxidant defense against the ingested toxic algae. Full article
(This article belongs to the Special Issue Chemical Defense in Marine Organisms)
Pharmaceutical Development and Safety Evaluation of a GMP-Grade Fucoidan for Molecular Diagnosis of Cardiovascular Diseases
by Cédric Chauvierre , Rachida Aid-Launais , Joël Aerts , Frédéric Chaubet , Murielle Maire , Lucas Chollet , Lydia Rolland , Roberta Bonafé , Silvia Rossi , Simona Bussi , Claudia Cabella , Laszlo Dézsi , Tamas Fülöp , Janos Szebeni , Youssef Chahid , Kang H. Zheng , Erik S. G. Stroes , Dominique Le Guludec , François Rouzet and Didier Letourneur
The adhesion molecule P-selectin is present on the cell surface of both activated endothelium and activated platelets. The present study describes the pharmaceutical development, safety evaluation, and preclinical efficacy of a micro-dosed radiotracer. The macromolecular nanoscale assembly consisted of a natural compound made [...] Read more.
The adhesion molecule P-selectin is present on the cell surface of both activated endothelium and activated platelets. The present study describes the pharmaceutical development, safety evaluation, and preclinical efficacy of a micro-dosed radiotracer. The macromolecular nanoscale assembly consisted of a natural compound made of a sulfated fucose-rich polysaccharides (fucoidan) and a radionuclide (technetium-99m) for the detection of P-selectin expression in cardiovascular diseases. After extraction and fractionation from brown seaweeds, the good manufacturing practice (GMP) production of a low molecular weight (LMW) fucoidan of 7 kDa was achieved and full physicochemical characterization was performed. The regulatory toxicology study in rats of the GMP batch of LMW fucoidan revealed no adverse effects up to 400 μg/kg (×500 higher than the expected human dose) and pseudoallergy was not seen as well. In a myocardial ischemia-reperfusion model in rats, the GMP-grade LMW fucoidan labeled with technetium-99m detected P-selectin upregulation in vivo. The present study supports the potential of using 99mTc-fucoidan as an imaging agent to detect activated endothelium in humans. Full article
(This article belongs to the Special Issue Vascular Bioactivities of Marine Natural Products)
Enhypyrazinones A and B, Pyrazinone Natural Products from a Marine-Derived Myxobacterium Enhygromyxa sp.
by Fan Zhang , Doug R. Braun , Scott R. Rajski , Don DeMaria and Tim S. Bugni
To date, studies describing myxobacterial secondary metabolites have been relatively scarce in comparison to those addressing actinobacterial secondary metabolites. This realization suggests the immense potential of myxobacteria as an intriguing source of secondary metabolites with unusual structural features and a wide array of [...] Read more.
To date, studies describing myxobacterial secondary metabolites have been relatively scarce in comparison to those addressing actinobacterial secondary metabolites. This realization suggests the immense potential of myxobacteria as an intriguing source of secondary metabolites with unusual structural features and a wide array of biological activities. Marine-derived myxobacteria are especially attractive due to their unique biosynthetic gene clusters, although they are more difficult to handle than terrestrial myxobacteria. Here, we report the discovery of two new pyrazinone-type molecules, enhypyrazinones A and B, from a marine-derived myxobacterium Enhygromyxa sp. Their structures were elucidated by HRESIMS and comprehensive NMR data analyses. Compounds 1 and 2, which contain a rare trisubstituted-pyrazinone core, represent a unique class of molecules from Enhygromyxa sp. Full article
Effect of Oral Administration of Active Peptides of Pinctada Martensii on the Repair of Skin Wounds
by Faming Yang , Xiaoming Qin , Ting Zhang , Chaohua Zhang and Haisheng Lin
Skin wound healing, especially chronic wound healing, is a common challenging clinical problem. It is urgent to broaden the sources of bioactive substances that can safely and efficiently promote skin wound healing. This study aimed to observe the effects of active peptides (APs) [...] Read more.
Skin wound healing, especially chronic wound healing, is a common challenging clinical problem. It is urgent to broaden the sources of bioactive substances that can safely and efficiently promote skin wound healing. This study aimed to observe the effects of active peptides (APs) of the mantle of Pinctada martensii on wound healing. After physicochemical analysis of amino acids and mass spectrometry of APs, the effect of APs on promoting healing was studied through a whole cortex wound model on the back of mice for 18 consecutive days. The results showed that APs consisted of polypeptides with molecular weights in the range 302.17–2936.43 Da. The content of polypeptides containing 2–15 amino acids accounted for 73.87%, and the hydrophobic amino acids accounted for 56.51%. Results of in vitro experimentation showed that mice in APs-L group which were fed a low dose of APs (0.5 g/kg bw) had a shortened epithelialization time due to a shortening inflammatory period (p < 0.05). Mechanistically, this relied on its specific ability to promote the proliferation of CD31, FGF and EGF which accelerated the percentage of wound closure. Moreover, the APs-L group mice had enhanced collagen synthesis and increased type III collagen content in their wounds through a TGF-β/Smad signaling pathway (p > 0.05). Consequently, scar formation was inhibited and wound healing efficiency was significantly improved. These results show that the APs of Pinctada martensii promote dermal wound healing in mice and have tremendous potential for development and utilization in skin wound healing. Full article
Discovery of Geranylgeranyl Pyrophosphate Synthase (GGPPS) Paralogs from Haematococcus pluvialis Based on Iso-Seq Analysis and Their Function on Astaxanthin Biosynthesis
by Danqiong Huang , Wenfu Liu , Anguo Li , Chaogang Wang and Zhangli Hu
Haematococcus pluvialis is widely distributed in the world and well known as the richest natural source of astaxanthin that is a strong antioxidant with excellent commercial value. The pathway of astaxanthin biosynthesis in H. pluvialis has been documented as an enzymatic reaction. Several [...] Read more.
Haematococcus pluvialis is widely distributed in the world and well known as the richest natural source of astaxanthin that is a strong antioxidant with excellent commercial value. The pathway of astaxanthin biosynthesis in H. pluvialis has been documented as an enzymatic reaction. Several enzymes have been reported, but their isoforms or homologs have not been investigated genome-wide. To better understand the astaxanthin biosynthesis pathway in H. pluvialis, eight candidates of the geranylgeranyl pyrophosphate synthase gene (HpGGPPS) predicted from Iso-seq data were isolated in this study. The length of coding region of these candidates varied from 960 bp to 1272 bp, composing of 7–9 exons. The putative amino acids of all candidates composed the signature domain of GGPPS gene. However, the motifs in the domain region are varied, indicating different bio-functions. Phylogenetic analysis revealed eight candidates can be clustered into three groups. Only two candidates in Group1 encode the synthase participating in the astaxanthin formation. The yield of astaxanthin from these two candidates, 7.1 mg/g (DW) and 6.5 mg/g (DW) respectively, is significant higher than that from CrtE (2.4 mg/g DW), a GGPPS gene from Pantoea ananatis. This study provides a potential productive pathway for astaxanthin synthesis. Full article
(This article belongs to the Special Issue Synthetic and Biosynthetic Approaches to Marine Natural Products)
A Cold-Adapted Chitinase-Producing Bacterium from Antarctica and Its Potential in Biocontrol of Plant Pathogenic Fungi
by Kezhen Liu , Haitao Ding , Yong Yu and Bo Chen
To obtain chitinase-producing microorganisms with high chitinolytic activity at low temperature, samples collected from Fildes Peninsula in Antarctica were used as sources for bioprospecting of chitinolytic microorganisms. A cold-adapted strain, designated as GWSMS-1, was isolated from marine sediment and further characterized as Pseudomonas [...] Read more.
To obtain chitinase-producing microorganisms with high chitinolytic activity at low temperature, samples collected from Fildes Peninsula in Antarctica were used as sources for bioprospecting of chitinolytic microorganisms. A cold-adapted strain, designated as GWSMS-1, was isolated from marine sediment and further characterized as Pseudomonas. To improve the chitinase production, one-factor-at-a-time and orthogonal test approaches were adopted to optimize the medium components and culture conditions. The results showed that the highest chitinolytic activity (6.36 times higher than that before optimization) was obtained with 95.41 U L−1 with 15 g L−1 of glucose, 1 g L−1 of peptone, 15 g L−1 of colloid chitin and 0.25 g L−1 of magnesium ions contained in the medium, cultivated under pH 7.0 and a temperature of 20 °C. To better understand the application potential of this strain, the enzymatic properties and the antifungal activity of the crude chitinase secreted by the strain were further investigated. The crude enzyme showed the maximum catalytic activity at 35 °C and pH 4.5, and it also exhibited excellent low-temperature activity, which still displayed more than 50% of its maximal activity at 0 °C. Furthermore, the crude chitinase showed significant inhibition of fungi Verticillium dahlia CICC 2534 and Fusarium oxysporum f. sp. cucumerinum CICC 2532, which can cause cotton wilt and cucumber blight, respectively, suggesting that strain GWSMS-1 could be a competitive candidate for biological control in agriculture, especially at low temperature. Full article
Inhibitory Effect of Depolymerized Sulfated Galactans from Marine Red Algae on the Growth and Adhesion of Diarrheagenic Escherichia coli
by Yixiang Liu , Wenqiang Liu , Yanbo Wang , Yu Ma , Ling Huang , Chao Zou , Donghui Li , Min-Jie Cao and Guang-Ming Liu
Active polysaccharides as safe and natural polymers against bacterial diarrhea have been reconsidered as an alternative to antibiotics. This work investigated the inhibiting effect of depolymerized sulfated galactans from Eucheuma serra and Gracilaria verrucosa on the growth and adhesion of diarrheagenic enterotoxigenic Escherichia [...] Read more.
Active polysaccharides as safe and natural polymers against bacterial diarrhea have been reconsidered as an alternative to antibiotics. This work investigated the inhibiting effect of depolymerized sulfated galactans from Eucheuma serra and Gracilaria verrucosa on the growth and adhesion of diarrheagenic enterotoxigenic Escherichia coli (ETEC) K88. Results showed that the sulfated polysaccharides with molecular weight distribution ≤20.0 kDa exhibited antibacterial activity against ETEC K88. A structure–activity study revealed that the anti-ETEC K88 activity of sulfated polysaccharides is strictly determined by their molecular weight distribution, sulfate group content, and monosaccharide composition. In addition, the promoted nucleic acid release and the fluorescence quenching of membrane proteins were observed after the treatment with selected polysaccharides. Scanning electron microscopy further confirmed that the depolymerized sulfated galactans can effectively inhibit ETEC K88 adhesion. In conclusion, depolymerized sulfated galactans exhibited an inhibitory effect on the growth and adhesion of ETEC K88. Full article
(This article belongs to the Special Issue Seaweeds Secondary Metabolites: Successes in and/or Probable Therapeutic Applications 2.0)
Supplementary File 1 (ZIP, 179819 KB)
Epinecidin-1 Protects against Methicillin Resistant Staphylococcus aureus Infection and Sepsis in Pyemia Pigs
by Han-Ning Huang , Chieh-Yu Pan , Bor-Chyuan Su , Hung-Yi Wu and Jyh-Yih Chen
Methicillin resistant Staphylococcus aureus (MRSA) may be found on the skin, nose, and throats of long-term hospitalized patients. While MRSA infections are usually minor, serious infections and death may occur in immunocompromised or diabetic patients, or after exposure of MRSA to blood. This [...] Read more.
Methicillin resistant Staphylococcus aureus (MRSA) may be found on the skin, nose, and throats of long-term hospitalized patients. While MRSA infections are usually minor, serious infections and death may occur in immunocompromised or diabetic patients, or after exposure of MRSA to blood. This report demonstrates that the antimicrobial peptide (AMP) epinecidin-1 (Epi-1) efficiently protects against MRSA infection in a pyemia pig model. We first found that Epi-1 exhibits bactericidal activity against MRSA. Next, pharmacokinetic analysis revealed that Epi-1 was stable in serum for 4 h after injection, followed by a gradual decrease. This pharmacokinetic profile suggested Epi-1 may bind serum albumin, which was confirmed in vitro. Harmful effects were not observed for doses up to 100 mg/kg body weight in pigs. When Epi-1 was supplied as a curative agent 30 min post-infection, MRSA-induced abnormalities in blood uric acid (UA), blood urea nitrogen (BUN), creatine (CRE), GOT, and GPT levels were restored to normal levels. We further showed that the bactericidal activity of Epi-1 was higher than that of the antibiotic drug vancomycin. Epi-1 significantly decreased MRSA counts in the blood, liver, kidney, heart, and lungs of infected pigs. Elevated levels of serum C reactive protein (CRP), proinflammatory cytokine IL6, IL1β, and TNFα were also attenuated by Epi-1 treatment. Moreover, the MRSA genes, enterotoxin (et)-A, et-B, intrinsic methicillin resistance A (mecA), and methicillin resistance factor A (femA), were significantly reduced or abolished in MRSA-infected pigs after treatment with Epi-1. Hematoxylin and eosin staining of heart, liver, lung, and kidney sections indicated that Epi-1 attenuated MRSA toxicity in infected pigs. A survival study showed that the pyemia pigs infected with MRSA alone died within a week, whereas the pigs post-treated with 2.5 mg/kg Epi-1 were completely protected against death. The present investigation, thus, demonstrates that Epi-1 effectively protects pyemia pigs against pathogenic MRSA without major toxic side effects. Full article
Alginate Oligosaccharides Affect Mechanical Properties and Antifungal Activity of Alginate Buccal Films with Posaconazole
by Marta Szekalska , Magdalena Wróblewska , Monika Trofimiuk , Anna Basa and Katarzyna Winnicka
Sodium alginate and its oligosaccharides through potential antifungal properties might improve the activity of antifungal drugs enhancing their efficacy and potentially reducing the frequency of application. Mucoadhesive buccal films are oral dosage forms designed for maintaining both local or systemic drug effects and [...] Read more.
Sodium alginate and its oligosaccharides through potential antifungal properties might improve the activity of antifungal drugs enhancing their efficacy and potentially reducing the frequency of application. Mucoadhesive buccal films are oral dosage forms designed for maintaining both local or systemic drug effects and seem to be a very promising alternative to conventional oral formulations. Hence, in this study, mucoadhesive buccal films based on the alginate and its oligosaccharide oligomer composed predominantly of mannuronic acid for the administration of posaconazole-antifungal drug from the azole group were developed. As the polymer gelation method, a relatively new freeze-thaw technique was chosen. All prepared formulations were examined for pharmaceutical tests, swelling, mechanical, and mucoadhesive properties. In addition, the influence of sodium alginate (ALG) and alginate oligosaccharides (OLG) on POS antifungal activity on Candida species was performed. It was observed that film formulation containing 1% ALG and 1% OLG (F2) was characterized by optimal mucoadhesive and swelling properties and prolonged drug release up to 5 h. Additionally, it was shown that OLG affected the growth reduction of all tested Candida spp. The obtained data has opened the way for future research for developing OLG-based dosage forms, which might increase the activity of antifungal drugs. Full article
(This article belongs to the Special Issue Marine Polysaccharides in Pharmaceutical Applications)
One-Step Preparative Separation of Phytosterols from Edible Brown Seaweed Sargassum horneri by High-Speed Countercurrent Chromatography
by Menglu Xia , Chunping Liu , Lei Gao and Yanbin Lu
Sargassum horneri, a sargassaceae brown alga, is one of the main species in the subtidal seaweeds flora extensively distributed in the Yellow and East China Sea. It has been proven that the phytosterols are an important class of bioactive substances in S. [...] Read more.
Sargassum horneri, a sargassaceae brown alga, is one of the main species in the subtidal seaweeds flora extensively distributed in the Yellow and East China Sea. It has been proven that the phytosterols are an important class of bioactive substances in S. horneri. In this work, a counter-current chromatography approach is proposed for preparative separation of phytol and two analogue sterols from a crude extract of S. horneri. A two-phase solvent system composed of n-hexane-acetonitrile-methanol (5:5:6, v/v) was selected and optimized. The effects of rotary speed and flow rate on the retention of the stationary phase were carefully studied. Under the optimum conditions, phytol and two analogue sterols, fucosterol and saringosterol, were baseline separated, producing 19.8 mg phytol, 23.7 mg fucosterol, and 3.1 mg saringosterol from 300 mg of crude S. horneri extract in one-step separation. The purities of three target compounds were all above 85%. The structures of phytol and two sterols were identified by nuclear magnetic resonance spectroscopy. Full article
(This article belongs to the Special Issue Advancements in Purification, Isolation and Chemical Profiling to Expedite the Discovery of Marine Natural Products)
In Vivo Hepatoprotective Effects of a Peptide Fraction from Krill Protein Hydrolysates against Alcohol-Induced Oxidative Damage
by Soo Yeon Park , Ilekuttige Priyan Shanura Fernando , Eui Joeng Han , Min Ju Kim , Kyungsook Jung , Dong-Soo Kang , Chang-Bum Ahn and Ginnae Ahn
Background: Krill (Euphausia superba) represent the largest animal biomass on earth, and are a rich source of high-quality protein with essential amino acids. Krill-derived peptides are renowned for their antioxidant activities. Hence, these peptides may have protective effects against oxidative stress. [...] Read more.
Background: Krill (Euphausia superba) represent the largest animal biomass on earth, and are a rich source of high-quality protein with essential amino acids. Krill-derived peptides are renowned for their antioxidant activities. Hence, these peptides may have protective effects against oxidative stress. Alcoholic liver disease is a prevalent cause of death worldwide. The present study explores the hepatoprotective effects of krill peptide hydrolysate fractions against ethanol-induced liver damage in BALB/c mice. Methods: Hydrolysis was carried out by mimicking the gastrointestinal digestion environment and the filtrate was fractionated based on molecular weight (<1 kDa, 1–3 kDa, and >3 kDa). The 1–3 kDa fraction (KPF), which indicated the highest antioxidant effect, was further investigated for its effect on weight and survival rate increase in mice and its influence on serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and liver cholesterol levels. Moreover, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels were measured, followed by Nrf2 and HO-1 expression. Histopathology studies were conducted to assess hepatic tissue damage. Results: KPF enhanced the weight and survival rate of mice while reducing serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and liver cholesterol levels. Moreover, KPF upregulated SOD, CAT, and GPx in liver tissues, while downregulating tumor necrosis factor α and interleukin-6 mRNA expression. KPF further increased Nrf2 and HO-1 expression and suppressed ethanol-induced apoptotic proteins in the liver. Histopathology of KPF-treated mice showed less hepatic tissue damage compared to ethanol-treated mice. Conclusions: Hydrolysates and bioactive peptides prepared from krill can be employed as functional foods to enhance liver function and health. Further investigations of KPF could lead to the development of functional foods. Full article
(This article belongs to the Special Issue Marine Immunomodulators)
Innovative Green Technologies of Intensification for Valorization of Seafood and Their By-Products
by Fadila Al Khawli , Mirian Pateiro , Rubén Domínguez , José M. Lorenzo , Patricia Gullón , Katerina Kousoulaki , Emilia Ferrer , Houda Berrada and Francisco J. Barba
The activities linked to the fishing sector generate substantial quantities of by-products, which are often discarded or used as low-value ingredients in animal feed. However, these marine by-products are a prominent potential good source of bioactive compounds, with important functional properties that can [...] Read more.
The activities linked to the fishing sector generate substantial quantities of by-products, which are often discarded or used as low-value ingredients in animal feed. However, these marine by-products are a prominent potential good source of bioactive compounds, with important functional properties that can be isolated or up-concentrated, giving them an added value in higher end markets, as for instance nutraceuticals and cosmetics. This valorization of fish by-products has been boosted by the increasing awareness of consumers regarding the relationship between diet and health, demanding new fish products with enhanced nutritional and functional properties. To obtain fish by-product-derived biocompounds with good, functional and acceptable organoleptic properties, the selection of appropriate extraction methods for each bioactive ingredient is of the outmost importance. In this regard, over the last years, innovative alternative technologies of intensification, such as ultrasound-assisted extraction (UAE) and supercritical fluid extraction (SFE), have become an alternative to the conventional methods in the isolation of valuable compounds from fish and shellfish by-products. Innovative green technologies present great advantages to traditional methods, preserving and even enhancing the quality and the extraction efficiency, as well as minimizing functional properties' losses of the bioactive compounds extracted from marine by-products. Besides their biological activities, bioactive compounds obtained by innovative alternative technologies can enhance several technological properties of food matrices, enabling their use as ingredients in novel foods. This review is focusing on analyzing the principles and the use of UAE and SFE as emerging technologies to valorize seafoods and their by-products. Full article
(This article belongs to the Special Issue Aquaculture Wastes and By-products as Source of High Added Value Compounds: Extraction, and Health Aspects)
Potential Use of Seaweed Bioactive Compounds in Skincare—A Review
by Valentina Jesumani , Hong Du , Muhammad Aslam , Pengbing Pei and Nan Huang
Modern lifestyles have developed new attention on appearance and personal care which attract a huge number of consumers towards cosmetic products. The demand for a skincare product with natural ingredients is rapidly increasing. Seaweeds are major resources for in-demand active compounds with a [...] Read more.
Modern lifestyles have developed new attention on appearance and personal care which attract a huge number of consumers towards cosmetic products. The demand for a skincare product with natural ingredients is rapidly increasing. Seaweeds are major resources for in-demand active compounds with a wide variety of applications. The use of seaweed-derived ingredients in cosmetic products has increased in recent years as many scientific studies have proved the potential skincare properties of seaweed bioactive compounds. This review emphasizes possible skincare properties of seaweed bioactive compounds. The review outlines the mechanism involved in skin problems including hyperpigmentation, premature skin aging, and acne in the first part while the second part focuses on the promising application of seaweeds in skin protection by highlighting the bioactive compound responsible for their bioactivity. Full article
(This article belongs to the Special Issue Seaweeds Secondary Metabolites: Successes in and/or Probable Therapeutic Applications)
The Pharmacokinetics of Fucoidan after Topical Application to Rats
by Olga N. Pozharitskaya , Alexander N. Shikov , Ekaterina D. Obluchinskaya and Heikki Vuorela
Fucoidan, a fucose-rich polysaccharide from brown algae, has been used for transdermal formulations targeting inflammatory skin conditions, for the treatment of thrombosis, vascular permeability diseases, subcutaneous wounds, and burns. However, the pharmacokinetics of fucoidan after topical application has not been described. In this [...] Read more.
Fucoidan, a fucose-rich polysaccharide from brown algae, has been used for transdermal formulations targeting inflammatory skin conditions, for the treatment of thrombosis, vascular permeability diseases, subcutaneous wounds, and burns. However, the pharmacokinetics of fucoidan after topical application has not been described. In this study, an ointment (OF) containing 15% fucoidan was topically applied to rats at the doses of 50–150 mg/g. The anti-Xa activity was selected as the biomarker, and the amidolytic assay method was validated and applied for pharmacokinetic studies of fucoidan. Fucoidan in OF penetrated the skin and distributed into the skin, striated muscle, and plasma with AUC0–48 = 0.94 μg·h/g, 2.22 μg·h/g, and 1.92 µg·h/mL, respectively. The longest half-life for fucoidan was observed in plasma, then in striated muscle and skin. It was found that the pharmacokinetics of fucoidan after topical OF application was linear, in the range of 50–150 mg/kg. No accumulation of fucoidan in plasma was observed after repeated topical applications of 100 mg/kg during five days. Our results support the rationality of topical application of formulations with fucoidan. Full article
(This article belongs to the Special Issue Pharmacokinetic Research of Marine Drugs)
Cytotoxic Polyketides Isolated from the Deep-Sea-Derived Fungus Penicillium chrysogenum MCCC 3A00292
by Siwen Niu , Manli Xia , Mingliang Chen , Xiupian Liu , Zengpeng Li , Yunchang Xie , Zongze Shao and Gaiyun Zhang
The chemical examination of the solid cultures of the deep-sea-derived fungus Penicillium chrysogenum MCCC 3A00292 resulted in the isolation of three new versiol-type analogues, namely peniciversiols A–C (1–3), and two novel lactone derivatives, namely penicilactones A and B ( [...] Read more.
The chemical examination of the solid cultures of the deep-sea-derived fungus Penicillium chrysogenum MCCC 3A00292 resulted in the isolation of three new versiol-type analogues, namely peniciversiols A–C (1–3), and two novel lactone derivatives, namely penicilactones A and B (6 and 7), along with 11 known polyketides. The planar structures of the new compounds were determined by the comprehensive analyses of the high-resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR) data, while their absolute configurations were resolved on the basis of comparisons of the experimental electronic circular dichroism (ECD) spectra with the calculated ECD data. Compound 1 is the second example of versiols featuring a 2,3-dihydropyran-4-one ring. Additionally, compounds 6 and 7 are the first representatives of γ-lactone derivatives constructed by a 1,3-dihydroxy-5-methylbenzene unit esterifying with the α-methyl-γ-hydroxy-γ-acetic acid α,β-unsaturated-γ-lactone moiety and α-hydroxy-γ-methyl-γ-acetic acid α,β-unsaturated-γ-lactone unit, respectively. All of the isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines of BIU-87, ECA109, BEL-7402, PANC-1, and Hela-S3. Compound 1 exhibited a selective inhibitory effect against the BIU-87 cell line (IC50 = 10.21 μM), while compounds 4, 5, 8, and 12–16 showed inhibitory activities against the ECA109, BIU-87, and BEL-7402 cell lines with the IC50 values ranging from 7.70 to > 20 μM. Full article
Combination Formulation of Tetrodotoxin and Lidocaine as a Potential Therapy for Severe Arrhythmias
by Bihong Hong , Jianlin He , Qingqing Le , Kaikai Bai , Yongqiang Chen and Wenwen Huang
Severe arrhythmias—such as ventricular arrhythmias—can be fatal, but treatment options are limited. The effects of a combined formulation of tetrodotoxin (TTX) and lidocaine (LID) on severe arrhythmias were studied. Patch clamp recording data showed that the combination of LID and TTX had a [...] Read more.
Severe arrhythmias—such as ventricular arrhythmias—can be fatal, but treatment options are limited. The effects of a combined formulation of tetrodotoxin (TTX) and lidocaine (LID) on severe arrhythmias were studied. Patch clamp recording data showed that the combination of LID and TTX had a stronger inhibitory effect on voltage-gated sodium channel 1.5 (Nav1.5) than that of either TTX or LID alone. LID + TTX formulations were prepared with optimal stability containing 1 μg of TTX, 5 mg of LID, 6 mg of mannitol, and 4 mg of dextran-40 and then freeze dried. This formulation significantly delayed the onset and shortened the duration of arrhythmia induced by aconitine in rats. Arrhythmia-originated death was avoided by the combined formulation, with a decrease in the mortality rate from 64% to 0%. The data also suggests that the anti-arrhythmic effect of the combination was greater than that of either TTX or LID alone. This paper offers new approaches to develop effective medications against arrhythmias. Full article
In Vitro Antiproliferative Evaluation of Synthetic Meroterpenes Inspired by Marine Natural Products
by Concetta Imperatore , Gerardo Della Sala , Marcello Casertano , Paolo Luciano , Anna Aiello , Ilaria Laurenzana , Claudia Piccoli and Marialuisa Menna
Several marine natural linear prenylquinones/hydroquinones have been identified as anticancer and antimutagenic agents. Structure-activity relationship studies on natural compounds and their synthetic analogs demonstrated that these effects depend on the length of the prenyl side chain and on the type and position of [...] Read more.
Several marine natural linear prenylquinones/hydroquinones have been identified as anticancer and antimutagenic agents. Structure-activity relationship studies on natural compounds and their synthetic analogs demonstrated that these effects depend on the length of the prenyl side chain and on the type and position of the substituent groups in the quinone moiety. Aiming to broaden the knowledge of the underlying mechanism of the antiproliferative effect of these prenylated compounds, herein we report the synthesis of two quinones 4 and 5 and of their corresponding dioxothiazine fused quinones 6 and 7 inspired to the marine natural product aplidinone A (1), a geranylquinone featuring the 1,1-dioxo-1,4-thiazine ring isolated from the ascidian Aplidium conicum. The potential effects on viability and proliferation in three different human cancer cell lines, breast adenocarcinoma (MCF-7), pancreas adenocarcinoma (Bx-PC3) and bone osteosarcoma (MG-63), were investigated. The methoxylated geranylquinone 5 exerted the highest antiproliferative effect exhibiting a comparable toxicity in all three cell lines analyzed. Interestingly, a deeper investigation has highlighted a cytostatic effect of quinone 5 referable to a G0/G1 cell-cycle arrest in BxPC-3 cells after 24 h treatment. Full article
(This article belongs to the Special Issue Synthesis of Marine Natural Products and Molecules Inspired by Marine Substances)
Bisindole Alkaloids from a New Zealand Deep-Sea Marine Sponge Lamellomorpha strongylata
by Kavita Ragini , Andrew M. Piggott and Peter Karuso
Chemical investigation of the secondary metabolites of a rare New Zealand deep-sea sponge, Lamellomorpha strongylata, resulted in the isolation of twenty-one indole alkaloids, including two new bisindoles—(Z)-coscinamide D (1), (E)-coscinamide D (2)—and four compounds [...] Read more.
Chemical investigation of the secondary metabolites of a rare New Zealand deep-sea sponge, Lamellomorpha strongylata, resulted in the isolation of twenty-one indole alkaloids, including two new bisindoles—(Z)-coscinamide D (1), (E)-coscinamide D (2)—and four compounds isolated for the first time as natural products—lamellomorphamides A (3), B (4), C (5) and D (6). In addition, fifteen previously reported natural products were isolated, seven of which are seco analogs of hamacanthin alkaloids. The one sponge produces enantiomerically pure but opposite configurations of compounds that only differ in the number of bromines, suggesting enantiodivergent biosynthesis. In addition, four compounds were isolated as partial racemates, suggesting these compounds are biosynthesized via two independent routes. Full article
Bioactive Nitrogenous Secondary Metabolites from the Marine Sponge Genus Haliclona
by Jiaying Zhu , Yang Liu , Zijun Liu , Hao Wang and Huawei Zhang
Marine sponge genus Haliclona, one of the most prolific sources of natural products, contains over 600 species but only a small part of them had been classified and chemically investigated. On the basis of extensive literature search, this review firstly summarizes 112 [...] Read more.
Marine sponge genus Haliclona, one of the most prolific sources of natural products, contains over 600 species but only a small part of them had been classified and chemically investigated. On the basis of extensive literature search, this review firstly summarizes 112 nitrogenous secondary metabolites from classified and unclassified Haliclona sponges as well as from their symbiotic microorganisms. Most of these substances have only been found in Haliclona sponges, and display diverse bioactive properties with potential applications in new drug discovery. Full article
(This article belongs to the Special Issue Advances in Marine Alkaloids)
Cloning, Expression, and Characterization of a New Glycosaminoglycan Lyase from Microbacterium sp. H14
by Junhao Sun , Xu Han , Guanrui Song , Qianhong Gong and Wengong Yu
Glycosaminoglycan (GAG) lyase is an effective tool for the structural and functional studies of glycosaminoglycans and preparation of functional oligosaccharides. A new GAG lyase from Microbacterium sp. H14 was cloned, expressed, purified, and characterized, with a molecular weight of approximately 85.9 kDa. The [...] Read more.
Glycosaminoglycan (GAG) lyase is an effective tool for the structural and functional studies of glycosaminoglycans and preparation of functional oligosaccharides. A new GAG lyase from Microbacterium sp. H14 was cloned, expressed, purified, and characterized, with a molecular weight of approximately 85.9 kDa. The deduced lyase HCLaseM belonged to the polysaccharide lyase (PL) family 8. Based on the phylogenetic tree, HCLaseM could not be classified into the existing three subfamilies of this family. HCLaseM showed almost the same enzyme activity towards hyaluronan (HA), chondroitin sulfate A (CS-A), CS-B, CS-C, and CS-D, which was different from reported GAG lyases. HCLaseM exhibited the highest activities to both HA and CS-A at its optimal temperature (35 °C) and pH (pH 7.0). HCLaseM was stable in the range of pH 5.0–8.0 and temperature below 30 °C. The enzyme activity was independent of divalent metal ions and was not obviously affected by most metal ions. HCLaseM is an endo-type enzyme yielding unsaturated disaccharides as the end products. The facilitated diffusion effect of HCLaseM is dose-dependent in animal experiments. These properties make it a candidate for further basic research and application. Full article
Mar. Drugs, EISSN 1660-3397, Published by MDPI AG


text:
Conference – 2004 Discussion
In Conference 2004
A Snapshot of Inflation Targeting in its Adolescence
Can Central Bank Transparency Go Too Far?
A Perspective on Monetary Policy Transparency and Communication
News and Interest Rate Expectations: A Study of Six Central Banks
Inflation Measurement for Central Bankers
Inflation in Australia: Measurement and Modelling
Inflation Targeting and Japan: Why has the Bank of Japan not Adopted Inflation Targeting?
Wrap-up Discussion
Biographies of Contributors
List of Conference Participants
1. Stefan Palmqvist
The paper by Ellis Connolly and Marion Kohler is one of the first to analyse and evaluate what types of news drive interest rate futures in a panel of countries, and I credit them for putting together a very interesting data set. Regarding the relative importance of the different driving forces, their main findings can be summarised as:
domestic and foreign news are the most important driving forces;
policy surprises play a small role; and
central bank communication explains almost nothing, and this is true, in particular, for speeches.
While I find the paper interesting, the results provide somewhat of a puzzle. If central bank communication does not affect the predictability of interest rates, why do central banks talk so much? As an example, since 1999 the six members of the Executive Board of Sveriges Riksbank (the central bank of Sweden) gave in combination an average of about 35 speeches per year. On top of that, some speeches are published as press releases, and since 1999 the Riksbank has published about 80 press releases per year on average. Taken together, the speeches and press releases amount to more than two pieces of central bank communication every week of the year. In other words, in reality central banks communicate quite frequently, which seems puzzling in light of the findings by Ellis and Marion. In my discussion I will focus on some methodological issues that may at least partly explain this.
What horizon should we look at?
Ellis and Marion use interest rate futures of different maturities as the dependent variable in their analysis. The benchmark result in the paper is for the interest rate futures four quarters ahead. They note that the results are robust to different contracts, where the longest contract is two years and the shortest contract is one quarter. However, market participants are typically most interested in the very next monetary policy decision. As most countries have monetary policy meetings about 10 times a year, the next decision is typically only 2–4 weeks ahead. If a central bank communicates its views about the next decision, some 2–4 weeks ahead, a one quarter contract may not adequately pick up the effects of the communication.
For central bank communication to be effective, a speech should, of course, also affect interest rate futures with longer maturities than 2–4 weeks. On the other hand, communication may not have any effects at all on the very long horizon, say five years ahead. This is because the best five-year forecast probably is that the economy is back at its steady state. I would, therefore, expect a speech to have a greater impact on interest rate futures with a shorter maturity than on interest rate futures with longer maturities. Thus, to evaluate the importance of a speech it may be necessary to look at an even shorter horizon than one quarter.
While speeches predominantly are concerned with the very next policy decision, other pieces of central bank communication may regard a somewhat longer period. As an example, inflation reports typically lay out the central bank's view about the outlook for the next 1–2 years. Therefore, an inflation report may affect interest rate futures with longer maturities. However, this is only partially confirmed by the results presented in Figure 5. Monetary policy reports in the US and New Zealand have a greater impact on the longer horizon futures, whereas the effects are more evenly distributed across different horizons in Australia, and in the other three economies the effects decrease with the horizon. There are some institutional differences between the economies that could help explain why monetary policy reports have different effects in the economies studied, and I think it is unfortunate that these institutional differences are not discussed in the paper (more on this below).
When it comes to the speeches, the effects of speeches are only shown for Australia and the panel consisting of all six economies. Thus, further study of the horizon at which different pieces of central bank communication affect the market should be an important area for future research.
Endogeneity
Another methodological issue is the potential endogeneity of central bank communication, especially with regards to speeches. In Sweden, the Executive Board members are constantly informed about what the market expects them to do with the policy rate at the next monetary policy meeting. If their own views differ from what the market expects, they can schedule a speech and 'correct' the market. I am aware of a few instances where this has happened in Sweden, and I suspect that the central banks that Ellis and Marion study follow similar procedures regarding the scheduling of speeches. In other words, the number of speeches may respond to developments in the interest rate futures markets, which can cause problems in the estimations that are conducted in the paper.
Much of a central bank's communication is about the economic outlook, including what the central bank expects the next CPI or GDP figure to be. Hence, the question is whether the effects of speeches and macroeconomic news can be identified separately. Suppose that a central bank was a 'black box' that did not communicate anything. If nobody knew the objectives of monetary policy or the central bank's framework for setting interest rates, interest rates would be completely unpredictable and no macroeconomic news would enter significantly in Ellis and Marion's estimations. I would argue that it is because central banks are transparent about their objectives, their framework for setting interest rates, and the outlook that the market can interpret what the outcome of a particular CPI or GDP figure implies for future interest rates. This suggests that it may not be possible to separate the effects of macroeconomic news from the effects of central bank communication.
As all economies studied in the paper have central banks that, to some extent, can be thought of as targeting inflation, it would also be interesting to include some other countries that are not as transparent about their objectives. Does macroeconomic news affect interest futures in a country where the central bank does not communicate its outlook, or is it the combination of communication and macroeconomic news that alter the markets' expectations? I would encourage the use of a broader set of countries to shed some light on this issue.
Measurement errors
In the empirical implementation, the authors incorporate speeches as an explanatory variable measured as a dummy variable. However, as the authors mention, not all speeches are designed to affect market expectations. In other words, speeches that are designed to affect market expectations are measured with errors.
How big of a problem is this? In a standard OLS framework, measurement errors in the explanatory variable do not pose a big problem, as they basically only add more noise to the equation. However, there are reasons to expect that they pose a greater problem in the EGARCH-framework that the authors use. Not only do the measurement errors add variance to the variance equation – the only equation where central bank communication enters – there is also reason to believe that these measurement errors could be serially correlated. As an example, while the total number of speeches by the Riksbank's Executive Board members decreased during 2001–03, the number of speeches on the topic of EMU/euro increased. That EMU/euro became a more frequent topic of speeches was a natural consequence of the Swedish referendum on whether Sweden should join the EMU and adopt the Euro that was held in September 2003. Given the outcome of the referendum, where a strong majority of the Swedish population voted against joining the EMU, there were almost no speeches held on the topic of EMU/euro after the referendum. In this particular example, any speech on the topic of the EMU/euro during this period is an example of a measurement error in the dummy variable for speeches and the gradual increase and sudden stop of speeches on this topic is a clear example of serial correlation.
While the example above refers to the case of Sweden, I suspect that similar examples can be found in the economies studied in the paper. Serially-correlated measurement errors may harm the results in the EGARCH model. One way of fixing the problem is of course to read all speeches and determine which ones have monetary policy content. As the number of speeches in the data set is quite large, reading all speeches to determine which ones have monetary policy content may not be feasible. A simpler way to check the robustness of the results is, therefore, to let a search engine look for certain phrases that may indicate whether the speech is intended to affect market expectations and only use those speeches in the estimations.
In summary, all these methodological issues could very well explain why Ellis and Marion find that central bank communication does not have a significant effect on the markets' expectation of future policy. I think these issues must be addressed before we can conclude that central bank communication does not add to transparency, as measured by the predictability of interest rates. That said, I would also strongly recommend that the authors pursue this line of research and explore further the interplay between the institutional framework and the effectiveness of different channels of communication. As an example, the forecasts in the inflation reports of the different countries are based on different conditioning assumptions. Some are based on a constant interest rate, some are based on the markets' expectations and some are measures of 'optimal policy'. A casual inspection of Table 7 seems to indicate that reports with unconditional forecasts have a greater impact on the longer-horizon futures than reports with constant interest rate forecasts. Another institutional difference is the size of the monetary policy committee. Do speeches have a greater effect if they are given by the single decision-maker than if a speech is given by one of the many members of a committee? These types of institutional differences deserve further exploration in the future.
2. General Discussion
A common theme in the discussion was how the results of the paper should be interpreted, with a number of participants questioning whether a finding of significance implied that central bank communication had been successful or unsuccessful. The authors responded that the framework used in the paper implied that the results could not distinguish between a central bank that communicates with perfect clarity and a central bank whose communication provides no useful information. Presumably, the strategy and thinking of the former is so well understood that their communication regarding economic developments will have no measurable effect on financial markets; the same would be true, however, of a central bank that says a lot without providing any real sense of its policy framework or how it interprets economic developments. The authors added that the central banks examined in the paper were all construed as having 'best-practice' communication strategies and, as such, if communication had an effect on financial markets, this was likely to be the deliberate intention of the central bank.
There was some discussion of how financial markets perceive central bank communication. One participant suggested that markets generally understand that central banks faced an output and inflation trade-off and, like the markets, have difficulties forecasting inflation and output. The nuances in central bank communication thus become quite important, as market participants might ascertain new insights as to the likely direction of policy. Another participant suggested that one reason why central bank communication seems to have a limited impact could be that markets have developed a good understanding of the central bank's policy reaction function. Hence, when macroeconomic data are released, the interest rate outlook is evident and there is not much additional information that a central bank, on most occasions, can convey about that outlook.
The role of central bank speeches was also discussed. A number of participants suggested that it was not surprising that speeches had such a limited effect on interest rate volatility. A possible reason for this, stressed by the authors, was that all speeches were contained in the data set, not only speeches that focused on monetary policy considerations. One participant suggested that many speeches were not intended to convey new information to financial markets or to foreshadow the decisions that will be taken by the policy committee. Instead, speeches are often made to reinforce the overall logic or framework of policy to the public and to address their concerns. In a similar vein, another participant suggested that because central banks' speeches were designed to help clarify the monetary policy framework, much of the effect of clear communication will be captured by the response of the markets to macroeconomic news. Another participant suggested that there were difficulties comparing the impact of speeches across countries because of differences in the content and length of speeches and their relationship to other forms of communication. This consideration was also clearly relevant for other forms of central bank communication.
Some participants queried the results for particular countries. One participant noted that markets pay relatively limited attention to the Federal Reserve's report to Congress, given that Chairman Alan Greenspan's testimony to Congress is held on the same day. It was also suggested that there was a case for splitting the speeches by US Federal Reserve officials into speeches by Greenspan and speeches by others, given that Greenspan was the dominant decision-maker. The authors suggested that distinguishing speeches according to their likely importance is a subjective exercise and, in any case, can amount to 'picking the winner', thus making a statistically significant result for speeches not very meaningful. A number of participants questioned the results for New Zealand in Figures 4 and 5, which show the increase in interest rate volatility following parliamentary hearings and the release of monetary policy reports. The authors responded that these results needed to be treated cautiously, as liquidity in NZ markets was relatively low at longer horizons, and there were estimation difficulties as different forms of communication often occur on the same day. The comparatively smaller impact of euro area macroeconomic news on financial markets might reflect the relatively long lag for the release of data and the apparent leaking of official data. Finally, one participant suggested that there was a marked change in the formation of market expectations in Canada following the adoption of fixed action dates for monetary policy decisions in December 2000. The finding that the largest sensitivity is to US news and domestic monetary policy action may thus be affected by the period when interest rate moves were basically unscheduled.

redpajama_set_name: RedPajamaCommonCrawl


text:
Mercury-Atlas 5 var en amerikansk uppskjutning i Mercuryprogrammet.

Uppdraget för Mercury 5 var bland annat att utröna om en varelse kunde utstå påverkan från den starka accelerationen (cirka 7 g) som Atlas raketen, gav. Uppdraget utfördes den 29 november 1961.

Besättningen, schimpansen Enos, överlevde och befanns vara vid gott mod efter landning.

Källor

Fotnoter

Rymdfarkoster
Mercuryprogrammet
1961 i USA
Rymdfartsåret 1961

redpajama_set_name: RedPajamaWikipedia


Featuring the High Mass Bias Gas Mask Core with Flip Block and new Violent Bite Reactive coverstock, the Black Widow Bite is what we moderately call "aggressive." The Black Widow Bite expands the performance offerings in the Black Widow series by offering a stronger hook motion with more aggressive backend. Take that as a warning.


Excellent report here on education spending titled "Counting the Cash for K-12: The Facts About Per-Pupil Spending in Colorado," published by the Independence Institute. While the report is focused on education spending in Colorado, they use national data in several instances for comparative purposes, and the information they provide is relevant to people across the country with an interest in K12 spending.
Their primary conclusion is that we should look less at how much we spend per student and more at how we're spending, since school budgets and per-pupil spending do not correlate with achievement. What's more, people can manipulate or reframe spending figures to make them look better or worse depending on their purposes – a trick that can confuse the entire discussion.
An analysis by a professor at Stanford found that only 27 of 163 studies showed a positive relationship between per-pupil spending and student performance. Two-thirds of those studies showed insignificant correlations, and the rest actually showed a negative relationship.
According to data from NCES, there is no significant relationship between per-pupil spending and NAEP scores, nor is there a correlation between an increase in spending and a change in NAEP scores over a 10 year period.
Well worth reading the entire report to learn more about real spending, manipulation of numbers for political purposes, and the lack of correlation between spending numbers and student achievement.


It's been said that California knows how to party. By the looks of things in Fontana, we'd have to agree.
We took a tour around the infield at Auto Club Speedway and found plenty of bicycles, barbeques and even a couple creative coifs.
For more pictures of infield fun in Fontana, CLICK HERE.


text:
...ТЫ и Я
Big thanks to Liam Murphy (via HS) for this image of a resourceful robin's nest!
Recoverism and the Arts: Driving change through collaborative research
What a day! The first major Recoverist event took place in the Manchester School of Art last Tuesday with around 150 people attending from around the UK, Italy, Germany, France and Lithuania. My personal thanks to Sarah G, Rob R, Lucy W of SUAB and Mark P and to all those who contributed on the day. The event was in part, about sharing new ideas and innovative practice that bridges substance misuse and recovery, with the arts - moving away from cliched representations of addiction, and critically about exploring ways in which art and artists might have a part in the research agenda. So the Recoverist movement is growing and as projects unfold, you can read about them here first. Thanks to the Arts & Health Research Group at the Manchester School of Art and for Alcohol Research UK for their generous funding.
Distant Voices - Coming Home
Professor Fergus McNeill - University of Glasgow
Alison Urie - Vox Liminis
Wednesday 24 May 2017 at the Media Factory, Innovation Studio, 3.00 to 5.30
'Distant Voices – Coming Home' is a project that responds to pressing public policy and political challenges created by huge rises in the numbers of people subject to penal sanctions and by high levels of reoffending. Turning conventional understandings of 'offender rehabilitation' on their head, the project is concerned not with 'correcting offenders' but rather with exploring and changing how they are received when 'coming home' after punishment. Distant Voices combines creative practices (principally song writing and sharing) research and knowledge exchange to enable dialogue and learning about re/integration - and to practice and experience it. This is a Cross–Disciplinary Seminar Series organised by the always brilliant Psychosocial Research Unit from the School of Social Work, Care and Community. More details and booking HERE.
BUPA Foundation - Healthy Futures: Empowering Young Adults
The BUPA Foundation has launched a new funding round through its Healthy Futures funding programme. The Bupa UK funds practical projects to tackle challenges in health and social care and make a direct impact on people's health and wellbeing. This funding round is focused on young adults aged 18 to 25 and the Foundation is specifically interested in projects that will have a positive impact on the health and wellbeing of young adults who face ongoing health challenges. The closing date for applications is the 19th May 2017. Read more HERE.
Celf o Gwmpas - Freelance Project Co-ordinator (Wales)
Deadline: Friday 28 April 2017 at 5pm
Celf o Gwmpas are looking for a new person to fill an exciting role and join our busy team at Centre Celf in Llandrindod Wells. The post will be a freelance position for a period of 9 months, starting early in May 2017. Celf o Gwmpas wishes to engage an individual with knowledge and experience of Arts, Health and Wellbeing to co-ordinate our current projects 'Reaching Out, Drawing In' and 'In Residence' and to develop our 'Artist Network'. The rate of pay for the work is £11.45 per hour, working on average 14 hours per week. For further details and to download the Job Description and Application Form, please visit our website HERE.
Birth Rites Collection 2017 Biennial Competition for New Works in Collaboration with The Whitworth
Submissions for our Birth Rites Collection Bi-annual award are now open.
This is an opportunity for your work to become a permanent part of the Birth Rites Collection. Your work will be featured as a constant on the Birth Rites website, will tour with the collection where it will be shown in future exhibitions, be available for loan to external shows and will be part of any publications released in line with the collection. The works submitted will be considered by our judges, Helen Knowles, Birth Rites Curator and Poppy Bowers, curator at the Whitworth Art Gallery. The chosen works will be featured for one month on our website and showcased digitally at an event in September at the Whitworth Art Gallery for one night as part of the Thursday Lates Programme. Songbirds: Music Making in Hospital: Saturday 24th June, 2017At the showcase, one winner of the competition will be announced and their work will become part of the Birth Rites Collection. The prize winner will also be awarded a two-week residency at Birth Rites Collection. This opportunity will be a chance to embed yourself within the Midwifery School to research a new piece of work. In addition to securing a residency, Birth Rites Collection will provide accommodation and a stipend of £250 and the winning work will be included in the Birth Rites Collection.
Please email born@birthrites.org.uk with any queries.
Competition Brief link: http://docdro.id/EIkTmMq
Application Form link: http://docdro.id/9QedBug
More information on our website: http://www.birthritescollection.org.uk
Deadline: June 25th, 2017
Songbirds: Music Making in Hospital: Saturday 24th June, 2017
Music making in hospital provides opportunities for communication and interaction, placing patients at the heart of an individualised creative experience. This workshop will give an overview of the clinical, acoustic and emotional environment of a hospital and explore practical techniques used in bedside music making. Through a series of developmental exercises, you will have the opportunity to develop skills in person-centred, nonverbal music making, musical communication and conversation. You will also learn about the importance of observation skills within this setting and have the opportunity to try out a range of musical activities using voice, body and percussion. No musical knowledge is assumed in this workshop, but bring your instrument if you have one. With specialist practitioner Ros Hawley. Full Details HERE.
Over the last few years I've been working with Australian artist, Vic McEwan as part of his arts and health residency in the UK. This short film (below) is a teaser of some work I have been preparing as a participant observer with Vic, as he has worked in an around Alder Hey Children's Hospital and over some time we've spent together in Australia. Of course, none of this film is from Alder Hey, but is found footage that will be part of a series of presentations that he and I will deliver together over June and September 2017, and although this small film is wordless, it may offer some clue as to my presentation and the essay Critical Care which I'm working on for publication in September this year. You'll be able to catch Vic and I speaking about his work and some of my reflections on art, artists and health care at the Culture, Health and Wellbeing International Conference 2017, in Bristol. More details HERE.


Back in 2015, we reported about the Henn na Hotel in Japan. The first of its kind hotel was to be almost entirely staffed by robots. Several years have passed and hotel is powering off many of the robots finding the majority of guests prefer human attendants. It turns out there were a number of humans required to keep the robots charged and assist guests when their questions were too difficult for the robots to answer. After much feedback, the hotel is removing many of the robotic staff members, but will still have several robots as attractions.


text:
Thoughts on The End of Poverty
activism / books
Recently, I have been reading The End of Poverty by Jeffrey Sachs. The book's goal is to explain the unique opportunity that exists in our time: to eliminate extreme poverty in the world. Extreme poverty, in this case, is defined as the 1 billion+ people that live on less than $1 US per day.
Now. The book spends significant time looking into various problems that the poorest countries (mostly in Africa) face, from disease to geographic limitations to Western meddling and all kinds of other things. Aside from looking at the problems, it tries to look at real, practical, possible solutions.
One of the most frustrating, from an American perspective, is described like this:
The problem is the complete disconnect between the extent of the initiative [a 2002 aid program created by the Bush Administration] – $5 billion more per year by the third year – and the needs of the poor countries (on the order of $100 billion more per year between 2006-2015 to meet the Millennium Development Goals) and with the commitment of the United States to make "concrete efforts" to target 0.7 percent of GNP [the amount that has repeatedly been agreed upon as aid needed from developed nations]. The $5 billion represents less than 0.05 percent of U.S. GNP. Even more startling, not a single penny of the Millennium Challenge Account had been disbursed by late 2004.
This quote occurs in the context of a chapter that discusses the unanimous opinion that there is a link between aiding economic growth and U.S. national security. It looks into the pragmatic reasons that it is a good thing for us to give aid to help countries get out of extreme poverty.
Throughout the book, a common theme remains that United States foreign policy in the past couple of decades (both Democratic and Republican administrations) has been very good at talking about foreign aid, and very bad at doing anything about it. As defense budgets have risen, aid budgets have fallen, and it is easy to observe that we are not getting more secure.
Times like ours are contrasted with things like the Marshall Plan, in which our country realized that aiding the recovery of Europe, which included foreign aid over 1.0 percent of GNP. Leaders of our country at the time were well aware that an economically progressing Europe would lead to a more secure United States.
Many of the chapters in this book cover things that (should) evoke brokenness and compassion on the part of people in wealthy countries, and should contribute to action. The Millennium Development Goals can make and are making a difference in the world, as businesses and individuals contribute to the transformation of African villages.
But the saddening part is that governments are not contributing in any meaningful way, especially ours. Statistics and surveys show that we as American citizens believe that our government does far more for the poor in foreign countries than it does, and that we would support even more support than we think there is. It's mind-boggling. While this is not surprising to learn, it is difficult.


text:
Geografia
 Lagardelle – comune francese nella regione dell'Occitania
 Lagardelle-sur-Lèze – comune francese nella regione dell'Occitania

Persone
 Hubert Lagardelle – sindacalista francese


95% of all authors have to do the marketing for their books – even if they are the "lucky" ones who found a major, traditional publisher. Only celebrities and star-authors, such as James Patterson or Danielle Steel get publicity from their publishers. The question for authors is now: Why should they sell their manuscripts for a pittance to publishing houses at all, if these publishers are sending out a mass-press-release only and are otherwise not involved in the marketing part? What are they good for?
Authors are smart and able to start their own publishing business, REAL publishing, not POD and not Vanity Publishing: Finding and getting quotes or referrals for an editor, a book lay-out company or book designer, cover artist, e-book formatting company and a printer is not difficult.
is the work of a couple of days, researching all aspects of the publishing enterprise.
for your print-version of the book is not a problem, distributors mostly require just three books to be listed as a publishing business, and if authors have not written three books yet, they can band together with other authors to reach this minimum.
Aaron Shepard has written two books about the topic of book distribution: POD for Profit and Aiming at Amazon, both contain very detailed information for small publishers.
Be careful when choosing a name for your book publishing company. Keep the name neutrally and usable in a variety of languages. Avoid your or your books name and survey several professionals for their input. Last but not least do a name check before your spend money on registering or using the name.
for your book publishing business is preferable through your own savings. Try to find the most economical way to start your publishing business. Don't order any print runs before you have substantial orders, rather go in the beginning with a recommendable POD, such as CreateSpace. In several countries, such as USA or Germany for example, financing the creation of books has become main stream. Kickstarter, IndiGoGo or STARTNEXT (German) are crowd funding sources, writers can use.
In a former blog post we explained how to get an International Standard Book Number (ISBN) and bar codes in several countries.
How to get into the "Books in Print", the worldwide database and to register your book for FREE! with Bowker was the topic of other blog posts. https://savvybookwriters.wordpress.com/2011/08/31/important-expose-your-book-to-the-world/.
However it is extremely important to choose the right genre (or several) in order for your books ranking, e.g. on Amazon.
Check out a variety of online retailers to "put your eggs in many baskets".
and how to get relevant links are the topic of several former blog posts.
To read them all just click on Website & SEO (28 articles!) on the right hand side of our blog.
Advice and useful links for book layout, printing etc.
Finding freelancers for editing, design, proofreading, webdesign etc.
Re-blogging this article is encouraged, just use the tiny re-blog button on top of this page!
If you enjoyed this blog post, please feel free to check out all previous posts of this blog (there are more than 720 of them : ) if you haven't already. Why not sign up to receive them regularly by email? Just click on "Follow" in the upper line on each page – and then on "LIKE" next to it. There is also the "SHARE" button underneath each article where you can submit the article to Pinterest, Google+, Twitter, Chime.in, Facebook, Tumblr and StumpleUpon.
This was a great blog. Thank you for your input.
it is a series that includes tips on how to actually set up your publishing business, about book production, book distribution etc. and will continue Monday, November 25th, stay tuned.
Great bog and most helpful! Thanks. I have one question: If I already have a company that is in a different field, IT, can I rebrand that company as a Publisher, or create a division for the publishing of my own ebooks, PODs?
Absolutely fantastic! Exactly what I was looking for without knowing it!


March 3, 2019 marked an important landmark in our journey to end Israeli apartheid and work towards collective liberation of Palestinians and all oppressed peoples. That Sunday, the Student Government Organization (SGO) voted in favor of a resolution supporting Swarthmore Students for Justice in Palestine (SJP) and its divestment campaign. SJP's proposed resolution is responding to the call from Palestinian civil society for boycott, divestment and sanctioning of the state of Israel to end our own institution's complicity in the violation of Palestinian human rights. By choosing to divest from companies like Bank Hapoalim, Boeing, Caterpillar, Elbit Systems, Hewlett Packard Enterprise, Hyundai Heavy Industries, and Lockheed Martin, we add our voices to the broader international movement affirming Palestinian human rights. We also pressure such companies to end their activities that perpetuate Israeli human rights abuses and a brutal military occupation that is in blatant violation of international law.
With this victory, Swarthmore's student government joins a prominent history of BDS movements in the United States and around the globe. Thirty-nine student governments in the U.S. and Canada - and more student unions in South Africa, Brazil, Chile, Qatar, Ireland and the UK - have passed resolutions in support of divestment from Israeli Apartheid.
The broader Swarthmore community has been invaluable to these developments, providing both critical support and solidarity with SJP. Last semester, over half of the student body signed a petition in support of BDS, demonstrating the widespread desire for divestment. In addition, 16 student and alumni groups wrote letters of solidarity with SJP, further emphasizing the commonalities between the Palestinian freedom struggle and their own anti-oppressive struggles and identities. Without this level of student involvement, the BDS campaign would not be possible. We thank you for lending your voices and energy to our campaign, for it is in concert that we move towards liberation for all marginalized peoples.
The Student Government Organization's decision to support our resolution marks another important step towards institutional change. SGO has been an important partner in our work. We thank SGO for their leadership and willingness to use their platform to affirm Palestinian human rights, and we hope to collaborate further on future measures of institutional accountability.
There is still much to be done and, just as before, your support is critical to sustaining the BDS movement. In the coming weeks, we will be finalizing the resolution and releasing it to the campus community. In the meantime, ensuring the safety of students who support Palestinian human rights on campus and continuing to advocate against Israeli apartheid are SJP's primary objectives. During Israeli Apartheid Week, between March 18 and April 8, we will be hosting several activities and events to uplift oppressed voices and celebrate Palestinian culture, turning away from the dominant narrative of conflict. We hope you can join us for these events and look forward to the future of the BDS campaign at Swarthmore.


text:
Vintage Pulp Jun 28 2018
They drive each other crazy.
It's rare that we can't locate a copy of a U.S. film but it happens sometimes. This poster for Speed Crazy has a hot rod and juvie delinquent look to it that made us want to see the film, but the best we managed was finding a trailer on YouTube. We wanted to share the poster anyway, though, because we love it. We'll keep looking for this one, because who doesn't want to watch a b-flick about a homicidal hot rodder? The last one we saw, The Cool and the Crazy, was a blast, in that terrible sort of way we enjoy. Speed Crazy, which starred Brett Halsey and Yvonne Lime, premiered in the U.S. today in 1959.
Allied ArtistsSpeed CrazyBrett HalseyYvonne LimeSlick Slavinposter artcinema
SEARCH PULP INTERNATIONAL
The headlines that mattered yesteryear.
1950—The Great Brinks Robbery Occurs
In the U.S., eleven thieves steal more than $2 million from an armored car company's offices in Boston, Massachusetts. The skillful execution of the crime, with only a bare minimum of clues left at the scene, results in the robbery being billed as "the crime of the century." Despite this, all the members of the gang are later arrested.
1977—Gary Gilmore Is Executed
Convicted murderer Gary Gilmore is executed by a firing squad in Utah, ending a ten-year moratorium on Capital punishment in the United States. Gilmore's story is later turned into a 1979 novel entitled The Executioner's Song by Norman Mailer, and the book wins the Pulitzer Prize for literature.
1942—Carole Lombard Dies in Plane Crash
American actress Carole Lombard, who was the highest paid star in Hollywood during the late 1930s, dies in the crash of TWA Flight 3, on which she was flying from Las Vegas to Los Angeles after headlining a war bond rally in support of America's military efforts. She was thirty-three years old.
1919—Luxemburg and Liebknecht Are Killed
Rosa Luxemburg and Karl Liebknecht, two of the most prominent socialists in Germany, are tortured and murdered by the Freikorps. Freikorps was a term applied to various paramilitary organizations that sprang up around Germany as soldiers returned in defeat from World War I. Members of these groups would later become prominent members of the SS.
It's easy. We have an uploader that makes it a snap. Use it to submit your art, text, header, and subhead. Your post can be funny, serious, or anything in between, as long as it's vintage pulp. You'll get a byline and experience the fleeting pride of free authorship. We'll edit your post for typos, but the rest is up to you. Click here to give us your best shot.
Pulp art from around the web
Things you'd love to buy but can't anymore