scholarly journals Antiplasmodial Compounds from Deep-Water Marine Invertebrates

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 179
Author(s):  
Amy E. Wright ◽  
Jennifer E. Collins ◽  
Bracken Roberts ◽  
Jill C. Roberts ◽  
Priscilla L. Winder ◽  
...  
Keyword(s):  
Life Cycle ◽  
Early Life ◽  
Marine Invertebrates ◽  
Schizont Stage ◽  
Malaria Therapy ◽  
Stage Specificity ◽  
Bioassay Guided Fractionation ◽  
Novel Drug ◽  
Drug Leads ◽  
Emergence Of Resistance

Novel drug leads for malaria therapy are urgently needed because of the widespread emergence of resistance to all available drugs. Screening of the Harbor Branch enriched fraction library against the Plasmodium falciparum chloroquine-resistant strain (Dd2) followed by bioassay-guided fractionation led to the identification of two potent antiplasmodials; a novel diterpene designated as bebrycin A (1) and the known C21 degraded terpene nitenin (2). A SYBR Green I assay was used to establish a Dd2 EC50 of 1.08 ± 0.21 and 0.29 ± 0.02 µM for bebrycin A and nitenin, respectively. Further analysis was then performed to assess the stage specificity of the inhibitors antiplasmodial effects on the Dd2 intraerythrocytic life cycle. Exposure to bebrycin A was found to block parasite maturation at the schizont stage if added any time prior to late schizogony at 42 hours post invasion, (HPI). In contrast, early life cycle exposure to nitenin (prior to 18 HPI) was identified as crucial to parasite inhibition, suggesting nitenin may target the maturation of the parasite during the transition from ring to early trophozoite (6–18 HPI), a novel property among known antimalarials.

scholarly journals Marine Microbiome as a Source of Antimalarials

2019 ◽  
Vol 4 (3) ◽  
pp. 103
Author(s):  
Peter J. McCarthy ◽  
Bracken F. Roberts ◽  
Abigail Carbonell ◽  
Jill Roberts ◽  
Amy E. Wright ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Marine Invertebrates ◽  
Multidrug Resistant ◽  
Phenotypic Screening ◽  
Marine Microorganisms ◽  
Marine Microbes ◽  
Falciparum Strain ◽  
Microbial Extracts ◽  
Novel Drug ◽  
Drug Leads

It is important to discover novel antimalarial pharmacophores because of the widespread emergence of Plasmodium falciparum isolates resistant to the available drugs. Secondary metabolites derived from microbes associated with marine invertebrates are a valuable resource for the discovery of novel drug leads. However, the potential of marine microbes as a source of antimalarials has not been explored. We investigated the promise of marine microorganisms for the production of antimalarial activities by testing 2365 diverse microbial extracts using phenotypic screening of a multidrug resistant chloroquine resistant P. falciparum strain. We conducted counter screening against mammalian cells for the 317 active extracts that exhibited more than 70% inhibition at 1 µg/mL. The screen identified 17 potent bioactive leads from a broad range of taxa. Our results establish that the marine microbiome is a rich source of antiplasmodial compounds that warrants in depth exploration.

Phoronida

2017 ◽  
Author(s):  
Judith Fuchs
Keyword(s):  
Life Cycle ◽  
Small Group ◽  
Larval Stage ◽  
Intertidal Zone ◽  
Marine Invertebrates ◽  
Tree Of Life ◽  
General Morphology ◽  
Family Level ◽  
Planktonic Larval Stage

This chapter describes the taxonomy of Phoronida, a small group of exclusively marine invertebrates found in most of the world's oceans from the intertidal zone to about 400 metres depth. Phoronids are meroplanktonic with a planktonic larval stage usually less than 2 mm in length and a benthic adult whose length ranges from a few cm up to 50 cm. The chapter covers their life cycle, ecology, and general morphology. It includes a section that indicates the systematic placement of the taxon described within the tree of life, and lists the key marine representative illustrated in the chapter (usually to genus or family level). This section also provides information on the taxonomic authorities responsible for the classification adopted, recent changes which might have occurred, and lists relevant taxonomic sources.

Global temperature and life

2017 ◽  
Author(s):  
Andrew Clarke
Keyword(s):  
Life Cycle ◽  
Marine Invertebrates ◽  
Natural World ◽  
Death Valley ◽  
Cell Interior ◽  
Ground Temperatures ◽  
Thermal Limits ◽  
Air Temperatures ◽  
Continental Shelves ◽  
Multicellular Organisms

The extreme meteorological surface air temperatures recorded to date are –89.2 oC in Antarctica, and 56.7 oC in Death Valley, California. Ground temperatures can be higher or lower than these air temperatures. The bulk of oceanic water is cold (< 4 oC) and thermally stable. Whilst data on limits to survival attract considerable attention, the thermal limits to completion of the life cycle (which define the limits to life) are much less well known. Currently identified upper thermal limits for growth are 122 oC for archaeans, 100 oC for bacteria and ~60 oC for unicellular eukaryotes. No unicells appear to grow below –20 oC, a limit that is probably set by dehydration-linked vitrification of the cell interior. The lower thermal limits for survival in multicellular organisms in the natural world extend to at least –70 oC. However in all cases known to date, completion of the life cycle requires summer warmth and the lowest temperature for completion of a multicellular eukaryote life cycle appears to be ~0 oC for invertebrates in glacial meltwater and ~–2 oC for marine invertebrates and fish living on the continental shelves around Antarctica.

scholarly journals First person – Natalí Delorme and Leonardo Zamora

Biology Open ◽  
2021 ◽  
Vol 10 (12) ◽  
Keyword(s):  
Oxidative Stress ◽  
Life Cycle ◽  
New Zealand ◽  
Stress Response ◽  
Marine Invertebrates ◽  
Early Career ◽  
New Method ◽  
First Person ◽  
Early Career Researchers ◽  
Selection Of

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Natalí Delorme and Leonardo Zamora are co-first authors on ‘ A new method to localise and quantify oxidative stress in live juvenile mussels’, published in BiO. They are both researchers in the laboratory of Serean Adams at the Cawthron Institute, Nelson, New Zealand. Natalí's research interests centre around ecophysiology of marine invertebrates, particularly on the organisms' stress response. Leonardo is investigating the biology of commercially, ecologically and culturally relevant marine invertebrates throughout their life cycle.

scholarly journals Phylogeny-Guided Selection of Priority Groups for Venom Bioprospecting: Harvesting Toxin Sequences in Tarantulas as a Case Study

Toxins ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 488 ◽  
Author(s):  
Tim Lüddecke ◽  
Andreas Vilcinskas ◽  
Sarah Lemke
Keyword(s):  
Success Rate ◽  
Mechanisms Of Action ◽  
Rational Selection ◽  
Almost All ◽  
Novel Drug ◽  
Drug Leads ◽  
Novel Structures ◽  
Animal Venoms ◽  
Selection Of

Animal venoms are promising sources of novel drug leads, but their translational potential is hampered by the low success rate of earlier biodiscovery programs, in part reflecting the narrow selection of targets for investigation. To increase the number of lead candidates, here we discuss a phylogeny-guided approach for the rational selection of venomous taxa, using tarantulas (family Theraphosidae) as a case study. We found that previous biodiscovery programs have prioritized the three subfamilies Ornithoctoninae, Selenocosmiinae, and Theraphosinae, which provide almost all of the toxin sequences currently available in public databases. The remaining subfamilies are poorly represented, if at all. These overlooked subfamilies include several that form entire clades of the theraphosid life tree, such as the subfamilies Eumenophorinae, Harpactirinae, and Stromatopelminae, indicating that biodiversity space has not been covered effectively for venom biodiscovery in Theraphosidae. Focusing on these underrepresented taxa will increase the likelihood that promising candidates with novel structures and mechanisms of action can be identified in future bioprospecting programs.

Ultrafast shape recognition for similarity search in molecular databases

2007 ◽  
Vol 463 (2081) ◽  
pp. 1307-1321 ◽  
Author(s):  
Pedro J Ballester ◽  
W. Graham Richards
Keyword(s):  
Biological Activity ◽  
Three Dimensional ◽  
Molecular Shape ◽  
Scientific Disciplines ◽  
Distance Distributions ◽  
Molecular Databases ◽  
Hard Problems ◽  
Data Explosion ◽  
Novel Drug ◽  
Drug Leads

Molecular databases are routinely screened for compounds that most closely resemble a molecule of known biological activity to provide novel drug leads. It is widely believed that three-dimensional molecular shape is the most discriminating pattern for biological activity as it is directly related to the steep repulsive part of the interaction potential between the drug-like molecule and its macromolecular target. However, efficient comparison of molecular shape is currently a challenge. Here, we show that a new approach based on moments of distance distributions is able to recognize molecular shape at least three orders of magnitude faster than current methodologies. Such an ultrafast method permits the identification of similarly shaped compounds within the largest molecular databases. In addition, the problematic requirement of aligning molecules for comparison is circumvented, as the proposed distributions are independent of molecular orientation. Our methodology could be also adapted to tackle similar hard problems in other fields, such as designing content-based Internet search engines for three-dimensional geometrical objects or performing fast similarity comparisons between proteins. From a broader perspective, we anticipate that ultrafast pattern recognition will soon become not only useful, but also essential to address the data explosion currently experienced in most scientific disciplines.

Early Life Cycle Cost Estimation: Fiscal Stewardship with Engineered Resilient Systems

2017 ◽  
pp. 17-25
Author(s):  
Travis Moody ◽  
Robert Provine ◽  
Samantha Todd ◽  
Nicholas Tyler ◽  
Thomas R. Ryan ◽  
...  
Keyword(s):  
Life Cycle ◽  
Cost Estimation ◽  
Early Life ◽  
Life Cycle Cost
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