Screening of the Promising Direct Thrombin Inhibitors from Haematophagous Organisms. Part I: Recombinant Analogues and Their Antithrombotic Activity In Vitro

The success in treatment of venous thromboembolism and acute coronary syndromes using direct thrombin inhibitors has stimulated research aimed at finding a new anticoagulant from haematophagous organisms. This study deals with the comparison between hirudin-1 from Hirudomedicinalis(desirudin), being the first-known and most well-studied natural anticoagulant, along with recombinant analogs of haemadin from the leech Haemadipsa sylvestris, variegin from the tick Amblyomma variegatum, and anophelin from Anopheles albimanus. These polypeptides were chosen due to their high specificity and affinity for thrombin, as well as their distinctive inhibitory mechanisms. We have developed a universal scheme for the biotechnological production of these recombinant peptides as pharmaceutical substances. The anticoagulant activities of these peptides were compared using the thrombin amidolytic activity assay and prolongation of coagulation time (thrombin time, prothrombin time, and activated partial thromboplastin time) in mouse and human plasma. The preliminary results obtained suggest haemadin as the closest analog of recombinant hirudin-1, the active substance of the medicinal product Iprivask (Aventis Pharmaceuticals, USA) for the prevention of deep venous thrombosis in patients undergoing elective hip or knee replacement surgery. In contrast, variegin can be regarded as a natural analog of bivalirudin (Angiomax, The Medicines Company), a synthetic hirudin-1 derivative certified for the treatment of patients undergoing percutaneous coronary intervention and of patients with unstable angina pectoris after percutaneous transluminal coronary angioplasty.

Ellinaite, CaCr₂O₄, a new natural post-spinel oxide from Hatrurim Basin, Israel, and Juína kimberlite field, Brazil

Ellinaite, a natural analog of the post-spinel phase β-CaCr2O4, was discovered at the Hatrurim Basin, Hatrurim pyrometamorphic formation (the Mottled Zone), Israel, and in an inclusion within the super-deep diamond collected at the placer of the Sorriso River, Juína kimberlite field, Brazil. Ellinaite at the Hatrurim Basin is confined to a reduced rankinite–gehlenite paralava, where it occurs as subhedral grains up to 30 µm in association with gehlenite, rankinite and pyrrhotite or forms the rims overgrowing zoned chromite–magnesiochromite. The empirical formula of the Hatrurim sample is (Ca0.960Fe0.0162+Na0.012Mg0.003)0.992(Cr1.731V0.1833+Ti0.0683+Al0.023Ti0.0034+)2.008O4. The mineral crystallizes in the orthorhombic system, space group Pnma, unit-cell parameters refined from X-ray single-crystal data: a 8.868(9), b 2.885(3), c 10.355(11) Å, V 264.9(5) Å3 and Z=4. The crystal structure of ellinaite from the Hatrurim Basin has been solved and refined to R1=0.0588 based on 388 independent observed reflections. Ellinaite in the Juína diamond occurs within the micron-sized polyphase inclusion in association with ferropericlase, magnesioferrite, orthorhombic MgCr2O4, unidentified iron carbide and graphite. Its empirical formula is Ca1.07(Cr1.71Fe0.063+V0.06Ti0.03Al0.03Mg0.02Mn0.02)Σ1.93O4. The unit-cell parameters obtained from HRTEM data are as follows: space group Pnma, a 9.017, b 2.874 Å, c 10.170 Å, V 263.55 Å3, Z=4. Ellinaite belongs to a group of natural tunnel-structured oxides of the general formula AB2O4, the so-called post-spinel minerals: marokite CaMn2O4, xieite FeCr2O4, harmunite CaFe2O4, wernerkrauseite CaFe23+Mn4+O6, chenmingite FeCr2O4, maohokite MgFe2O4 and tschaunerite Fe(FeTi)O4. The mineral from both occurrences seems to be crystallized under highly reduced conditions at high temperatures (>1000 ∘C), but under different pressure: near-surface (Hatrurim Basin) and lower mantle (Juína diamond).

Natural Fe-bearing aluminous bridgmanite in the Katol L6 chondrite

Bridgmanite, the most abundant mineral of the Earth’s lower mantle, has been reported in only a few shocked chondritic meteorites; however, the compositions of these instances differ from that expected in the terrestrial bridgmanite. Here, we report the first natural occurrence of Fe-bearing aluminous bridgmanite in shock-induced melt veins within the Katol L6 chondrite with a composition that closely matches those synthesized in high-pressure and temperature experiments over the last three decades. The Katol bridgmanite coexists with majorite and metal-sulfide intergrowths. We found that the natural Fe-bearing aluminous bridgmanite in the Katol L6 chondrite has a significantly higher Fe3+/ΣFe ratio (0.69 ± 0.08) than coexisting majorite (0.37 ± 0.10), which agrees with experimental studies. The Katol bridgmanite is arguably the closest natural analog for the bridgmanite composition expected to be present in the Earth’s lower mantle. Textural observations and comparison with laboratory experiments suggest that the Katol bridgmanite formed at pressures of ∼23 to 25 gigapascals directly from the chondritic melt generated by the shock event. Thus, the Katol L6 sample may also serve as a unique analog for crystallization of bridgmanite during the final stages of magma ocean crystallization during Earth’s formation.

Seeking natural analogs to fast-forward the assessment of marine CO2 removal

Mitigating global climate change will require gigaton-scale carbon dioxide removal (CDR) as a supplement to rapid emissions reduction. The oceans cover 71% of the Earth surface and have the potential to provide much of the required CDR. However, none of the proposed marine CDR (mCDR) methods is sufficiently well understood to determine their real-world efficiency and environmental side effects. Here, we argue that using natural mCDR analogs should become the third interconnecting pillar in the mCDR assessment as they bridge the gap between numerical simulations (i.e., large scale/reduced complexity) and experimental studies (i.e., small scale/high complexity). Natural mCDR analogs occur at no cost, can provide a wealth of data to inform mCDR, and do not require legal permission or social license for their study. We propose four simple criteria to identify particularly useful analogs: 1) large scale, 2) abruptness of perturbation, 3) availability of unperturbed control sites, and 4) reoccurrence. Based on these criteria, we highlight four examples: 1) equatorial upwelling as a natural analog for artificial upwelling, 2) downstream of Kerguelen Island for ocean iron fertilization, 3) the Black and Caspian Seas for ocean alkalinity enhancement, and 4) the Great Atlantic Sargassum Belt for ocean afforestation. These natural analogs provide a reality check for experimental assessments and numerical modeling of mCDR. Ultimately, projections of mCDR efficacy and sustainability supported by observations from natural analogs will provide the real-world context for the public debate and will facilitate political decisions on mCDR implementation. We anticipate that a rigorous investigation of natural analogs will fast-forward the urgently needed assessment of mCDR.

Novel Bifunctional Acylase from Actinoplanes utahensis: A Versatile Enzyme to Synthesize Antimicrobial Compounds and Use in Quorum Quenching Processes

Many intercellular communication processes, known as quorum sensing (QS), are regulated by the autoinducers N-acyl-l-homoserine lactones (AHLs) in Gram-negative bacteria. The inactivation of these QS processes using different quorum quenching (QQ) strategies, such as enzymatic degradation of the autoinducers or the receptor blocking with non-active analogs, could be the basis for the development of new antimicrobials. This study details the heterologous expression, purification, and characterization of a novel N-acylhomoserine lactone acylase from Actinoplanes utahensis NRRL 12052 (AuAHLA), which can hydrolyze different natural penicillins and N-acyl-homoserine lactones (with or without 3-oxo substitution), as well as synthesize them. Kinetic parameters for the hydrolysis of a broad range of substrates have shown that AuAHLA prefers penicillin V, followed by C12-HSL. In addition, AuAHLA inhibits the production of violacein by Chromobacterium violaceum CV026, confirming its potential use as a QQ agent. Noteworthy, AuAHLA is also able to efficiently synthesize penicillin V, besides natural AHLs and phenoxyacetyl-homoserine lactone (POHL), a non-natural analog of AHLs that could be used to block QS receptors and inhibit signal of autoinducers, being the first reported AHL acylase capable of synthesizing AHLs.

Carbonate polymorphism controlled by microbial iron redox dynamics at a natural CO2 leakage site (Crystal Geyser, Utah)

Crystal Geyser (Utah, USA) is a CO2-rich low-temperature geyser that is studied as a natural analog for CO2 leakage from carbon capture and storage (CCS) sites. In order to better constrain the biogeochemical processes influencing CaCO3 precipitation at geological CO2 escape sites, we characterized fast-forming iron-rich calcium carbonate pisoids and travertines precipitating from the fluids expelled by the geyser. The pisoids, located within a few meters from the vent, are composed of concentric layers of aragonite and calcite. Calcite layers contain abundant ferrihydrite shrubs in which iron is encasing bacterial forms. The aragonite layers contain less abundant and finely dispersed iron, present either as iron-oxide microspherules or iron adsorbed to organic matter dispersed within the carbonate matrix. We propose that carbonate polymorphism in the pisoids is mostly controlled by local fluctuations of the iron redox state of the fluids from which they form, caused by episodic blooms of iron-oxidizing bacteria. Indeed, the waters expelled by Crystal Geyser contain >200 µM dissolved iron (Fe2+), a known inhibitor of calcite growth. The calcite layers of the pisoids may record episodes of intense microbial iron oxidation, consistent with observations of iron-oxide rich biofilms thriving in the rimstone pools around the geyser and previous metagenomic analyses showing abundant neutrophilic, microaerophilic iron-oxidizing bacteria in vent water. In turn, aragonite layers of the pisoids likely precipitate from Fe2+-rich waters, registering periods of less intense iron oxidation. Separately, CaCO3 polymorphism in the travertines, where calcite and aragonite precipitate concurrently, is not controlled by iron dynamics, but may be locally influenced by the presence of microbial biofilms. This study documents for the first time an influence of microbial iron oxidation on CaCO3 polymorphism in the environment, and informs our understanding of carbonate formation at CO2 leakage sites and in CCS contexts.

Circuit Covers of Signed Eulerian Graphs

A signed circuit cover of a signed graph is a natural analog of a circuit cover of a graph, and is equivalent to a covering of its corresponding signed-graphic matroid with circuits. It was conjectured that a signed graph whose signed-graphic matroid has no coloops has a 6-cover. In this paper, we prove that the conjecture holds for signed Eulerian graphs.

Hepatoprotective effect of piceatannol against carbon tetrachloride-induced liver fibrosis in mice

Piceatannol (3,5,3’,4’-trans-tetrahydroxystilbene) is a natural analog and a metabolite of resveratrol present in grapes and red wine. Previous studies have reported that piceatannol exerts a broad spectrum of health benefits...

Domination and Kwapień’s factorization theorems for positive Cohen p–nuclear m–linear operators

In this paper, we introduce and study the concept of positive Cohen p-nuclear multilinear operators between Banach lattice spaces. We prove a natural analog to the Pietsch domination theorem for this class. Moreover, we give like the Kwapień’s factorization theorem. Finally, we investigate some relations with another known classes.

AGROCHEMICAL PROPERTIES OF LEACHED APPLE ORCHARD CHERNOZEM COMPARED TO THE NATURAL ANALOG OF THE LIPETSK REGION

The article is devoted to the study of changes in soil properties in Apple orchards. During the operation of Apple orchards, 2 zones are formed in the soil – trunk strips and row spacing. In the row spacing in the 10-40 cm layer, due to the high density of the soil, Apple roots do not consume nutrients, and in the same layer in the trunk strips, acidification and removal of phosphorus, potassium, humus and bases occur. The nitrification capacity of the soil in the trunk strips of the old Apple orchard is at the level of virgin areas and increases as the soil decompresses.