scholarly journals Recent Developments on the Synthesis and Bioactivity of Ilamycins/Rufomycins and Cyclomarins, Marine Cyclopeptides That Demonstrate Anti-Malaria and Anti-Tuberculosis Activity

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 446
Author(s):  
Uli Kazmaier ◽  
Lukas Junk

Ilamycins/rufomycins and cyclomarins are marine cycloheptapeptides containing unusual amino acids. Produced by Streptomyces sp., these compounds show potent activity against a range of mycobacteria, including multidrug-resistant strains of Mycobacterium tuberculosis. The cyclomarins are also very potent inhibitors of Plasmodium falciparum. Biosynthetically the cyclopeptides are obtained via a heptamodular nonribosomal peptide synthetase (NRPS) that directly incorporates some of the nonproteinogenic amino acids. A wide range of derivatives can be obtained by fermentation, while bioengineering also allows the mutasynthesis of derivatives, especially cyclomarins. Other derivatives are accessible by semisynthesis or total syntheses, reported for both natural product classes. The anti-tuberculosis (anti-TB) activity results from the binding of the peptides to the N-terminal domain (NTD) of the bacterial protease-associated unfoldase ClpC1, causing cell death by the uncontrolled proteolytic activity of this enzyme. Diadenosine triphosphate hydrolase (PfAp3Aase) was found to be the active target of the cyclomarins in Plasmodia. SAR studies with natural and synthetic derivatives on ilamycins/rufomycins and cyclomarins indicate which parts of the molecules can be simplified or otherwise modified without losing activity for either target. This review examines all aspects of the research conducted in the syntheses of these interesting cyclopeptides.

Author(s):  
Aaron J. Cowieson ◽  
Franz F. Roos

SummaryA meta-analysis of the effect of a mono-component bacterial protease (RONOZYME® ProAct) on the apparent ileal digestibility of amino acids in poultry and swine diets was conducted to examine functional patterns, mean effects and variability of response. A total of 25 independently-conducted experiments were included comprising a total of 804 datapoints. The mean response to protease was +3.74% (SE 1.1%, P < 0.001) and this ranged from +5.6% for Thr (SE 1.2%, P < 0.001) to +2.7% for Glu (SE 1.2%, P < 0.05). For the most economically critical amino acids (Lys, Cys, Met and Thr) the mean response was 4.5%. The effect of protease was independent of geography, animal species and diet composition (P > 0.05). However, the inherent digestibility of amino acids in the control diet as a single explanatory term explained around 47% of the variance (P < 0.001) in effect. When the inherent digestibility of amino acids in the control diet was less than 70% protease addition improved amino acid digestibility in 90% of cases with a mean improvement of around 10%. When the inherent digestibility of amino acids in the control diet was more than 90% there was a protease-mediated improvement in digestibility in only 60% of cases with a mean improvement of around 2%. It can be concluded that the inherent digestibility of amino acids in the diet without protease supplementation is the primary explanatory term for the efficacy of this exogenous protease, demonstrating that it is highly effective in improving the digestibility of amino acids across a wide range of feed ingredients. Benchmarking diets or feed ingredients as to their relative nutritional value would enhance the ability of nutritionists to determine the likely return on investment on use of bacterial proteases in their operation.


The recycling and reuse of materials and objects were extensive in the past, but have rarely been embedded into models of the economy; even more rarely has any attempt been made to assess the scale of these practices. Recent developments, including the use of large datasets, computational modelling, and high-resolution analytical chemistry, are increasingly offering the means to reconstruct recycling and reuse, and even to approach the thorny matter of quantification. Growing scholarly interest in the topic has also led to an increasing recognition of these practices from those employing more traditional methodological approaches, which are sometimes coupled with innovative archaeological theory. Thanks to these efforts, it has been possible for the first time in this volume to draw together archaeological case studies on the recycling and reuse of a wide range of materials, from papyri and textiles, to amphorae, metals and glass, building materials and statuary. Recycling and reuse occur at a range of site types, and often in contexts which cross-cut material categories, or move from one object category to another. The volume focuses principally on the Roman Imperial and late antique world, over a broad geographical span ranging from Britain to North Africa and the East Mediterranean. Last, but not least, the volume is unique in focusing upon these activities as a part of the status quo, and not just as a response to crisis.


Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2237 ◽  
Author(s):  
P. R. Sarika ◽  
Paul Nancarrow ◽  
Abdulrahman Khansaheb ◽  
Taleb Ibrahim

Phenol–formaldehyde (PF) resin continues to dominate the resin industry more than 100 years after its first synthesis. Its versatile properties such as thermal stability, chemical resistance, fire resistance, and dimensional stability make it a suitable material for a wide range of applications. PF resins have been used in the wood industry as adhesives, in paints and coatings, and in the aerospace, construction, and building industries as composites and foams. Currently, petroleum is the key source of raw materials used in manufacturing PF resin. However, increasing environmental pollution and fossil fuel depletion have driven industries to seek sustainable alternatives to petroleum based raw materials. Over the past decade, researchers have replaced phenol and formaldehyde with sustainable materials such as lignin, tannin, cardanol, hydroxymethylfurfural, and glyoxal to produce bio-based PF resin. Several synthesis modifications are currently under investigation towards improving the properties of bio-based phenolic resin. This review discusses recent developments in the synthesis of PF resins, particularly those created from sustainable raw material substitutes, and modifications applied to the synthetic route in order to improve the mechanical properties.


Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 481
Author(s):  
Gemma G. Martínez-García ◽  
Raúl F. Pérez ◽  
Álvaro F. Fernández ◽  
Sylvere Durand ◽  
Guido Kroemer ◽  
...  

Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of atg4b−/− mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals.


Author(s):  
Hernâni Marques ◽  
Pedro Cruz-Vicente ◽  
Tiago Rosado ◽  
Mário Barroso ◽  
Luís A. Passarinha ◽  
...  

Environmental tobacco smoke exposure (ETS) and smoking have been described as the most prevalent factors in the development of certain diseases worldwide. According to the World Health Organization, more than 8 million people die every year due to exposure to tobacco, around 7 million due to direct ETS and the remaining due to exposure to second-hand smoke. Both active and second-hand exposure can be measured and controlled using specific biomarkers of tobacco and its derivatives, allowing the development of more efficient public health policies. Exposure to these compounds can be measured using different methods (involving for instance liquid- or gas-chromatographic procedures) in a wide range of biological specimens to estimate the type and degree of tobacco exposure. In recent years, a lot of research has been carried out using different extraction methods and different analytical equipment; this way, liquid–liquid extraction, solid-phase extraction or even miniaturized procedures have been used, followed by chromatographic analysis coupled mainly to mass spectrometric detection. Through this type of methodologies, second-hand smokers can be distinguished from active smokers, and this is also valid for e-cigarettes and vapers, among others, using their specific biomarkers. This review will focus on recent developments in the determination of tobacco smoke biomarkers, including nicotine and other tobacco alkaloids, specific nitrosamines, polycyclic aromatic hydrocarbons, etc. The methods for their detection will be discussed in detail, as well as the potential use of threshold values to distinguish between types of exposure.


1990 ◽  
Vol 43 (5) ◽  
pp. 583
Author(s):  
GL Price

Recent developments in the growth of semiconductor thin films are reviewed. The emphasis is on growth by molecular beam epitaxy (MBE). Results obtained by reflection high energy electron diffraction (RHEED) are employed to describe the different kinds of growth processes and the types of materials which can be constructed. MBE is routinely capable of heterostructure growth to atomic precision with a wide range of materials including III-V, IV, II-VI semiconductors, metals, ceramics such as high Tc materials and organics. As the growth proceeds in ultra high vacuum, MBE can take advantage of surface science techniques such as Auger, RHEED and SIMS. RHEED is the essential in-situ probe since the final crystal quality is strongly dependent on the surface reconstruction during growth. RHEED can also be used to calibrate the growth rate, monitor growth kinetics, and distinguish between various growth modes. A major new area is lattice mismatched growth where attempts are being made to construct heterostructures between materials of different lattice constants such as GaAs on Si. Also described are the new techniques of migration enhanced epitaxy and tilted superlattice growth. Finally some comments are given On the means of preparing large area, thin samples for analysis by other techniques from MBE grown films using capping, etching and liftoff.


2021 ◽  
Vol 7 (8) ◽  
pp. 593
Author(s):  
Jingjing Wang ◽  
Alexander Berestetskiy ◽  
Qiongbo Hu

Destruxin A (DA), a hexa-cyclodepsipeptidic mycotoxin produced by the entomopathogenic fungus Metarhizium anisopliae, exhibits insecticidal activities in a wide range of pests and is known as an innate immunity inhibitor. However, its mechanism of action requires further investigation. In this research, the interactions of DA with the six aminoacyl tRNA synthetases (ARSs) of Bombyx mori, BmAlaRS, BmCysRS, BmMetRS, BmValRS, BmIleRS, and BmGluProRS, were analyzed. The six ARSs were expressed and purified. The BLI (biolayer interferometry) results indicated that DA binds these ARSs with the affinity indices (KD) of 10−4 to 10−5 M. The molecular docking suggested a similar interaction mode of DA with ARSs, whereby DA settled into a pocket through hydrogen bonds with Asn, Arg, His, Lys, and Tyr of ARSs. Furthermore, DA treatments decreased the contents of soluble protein and free amino acids in Bm12 cells, which suggested that DA impedes protein synthesis. Lastly, the ARSs in Bm12 cells were all downregulated by DA stress. This study sheds light on exploring and answering the molecular target of DA against target insects.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 438
Author(s):  
Jingru Shi ◽  
Chen Chen ◽  
Dejuan Wang ◽  
Ziwen Tong ◽  
Zhiqiang Wang ◽  
...  

The emergence and prevalence of multidrug-resistant (MDR) bacteria have posed a serious threat to public health. Of particular concern are methicillin-resistant Staphylococcus aureus (MRSA) and blaNDM, mcr-1 and tet(X)-positive Gram-negative pathogens. The fact that few new antibiotics have been approved in recent years exacerbates this global crisis, thus, new alternatives are urgently needed. Antimicrobial peptides (AMPs) originated from host defense peptides with a wide range of sources and multiple functions, are less prone to achieve resistance. All these characteristics laid the foundation for AMPs to become potential antibiotic candidates. In this study, we revealed that peptide WW307 displayed potent antibacterial and bactericidal activity against MDR bacteria, including MRSA and Gram-negative bacteria carrying blaNDM-5, mcr-1 or tet(X4). In addition, WW307 exhibited great biofilm inhibition and eradication activity. Safety and stability experiments showed that WW307 had a strong resistance against various physiological conditions and displayed relatively low toxicity. Mechanistic experiments showed that WW307 resulted in membrane damage by selectively targeting bacterial membrane-specific components, including lipopolysaccharide (LPS), phosphatidylglycerol (PG), and cardiolipin (CL). Moreover, WW307 dissipated membrane potential and triggered the production of reactive oxygen species (ROS). Collectively, these results demonstrated that WW307 represents a promising candidate for combating MDR pathogens.


Author(s):  
Kevork Oskanian

Abstract This article contributes a securitisation-based, interpretive approach to state weakness. The long-dominant positivist approaches to the phenomenon have been extensively criticised for a wide range of deficiencies. Responding to Lemay-Hébert's suggestion of a ‘Durkheimian’, ideational-interpretive approach as a possible alternative, I base my conceptualisation on Migdal's view of state weakness as emerging from a ‘state-in-society's’ contested ‘strategies of survival’. I argue that several recent developments in Securitisation Theory enable it to capture this contested ‘collective knowledge’ on the state: a move away from state-centrism, the development of a contextualised ‘sociological’ version, linkages made between securitisation and legitimacy, and the acknowledgment of ‘securitisations’ as a contested Bourdieusian field. I introduce the concept of ‘securitisation gaps’ – divergences in the security discourses and practices of state and society – as a concept aimed at capturing this contested role of the state, operationalised along two logics (reactive/substitutive) – depending on whether they emerge from securitisations of the state action or inaction – and three intensities (latent, manifest, and violent), depending on the extent to which they involve challenges to state authority. The approach is briefly illustrated through the changing securitisation gaps in the Republic of Lebanon during the 2019–20 ‘October Uprising’.


Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2100
Author(s):  
Xu Zhang ◽  
Bowen Tan ◽  
Yanting Wu ◽  
Min Zhang ◽  
Jinfeng Liao

Photothermal treatment (PTT) is a promising strategy to deal with multidrug-resistant bacteria infection and promote tissue regeneration. Previous studies demonstrated that hyperthermia can effectively inhibit the growth of bacteria, whereas mild heat can promote cell proliferation, further accelerating wound healing and bone regeneration. Especially, hydrogels with photothermal properties could achieve remotely controlled drug release. In this review, we introduce a photothermal agent hybrid in hydrogels for a photothermal effect. We also summarize the potential mechanisms of photothermal hydrogels regarding antibacterial action, angiogenesis, and osteogenesis. Furthermore, recent developments in photothermal hydrogels in wound healing and bone regeneration applications are introduced. Finally, future application of photothermal hydrogels is discussed. Hydrogels with photothermal effects provide a new direction for wound healing and bone regeneration, and this review will give a reference for the tissue engineering.


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