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Complement factor D (FD) is a serine protease present predominantly in the active form in circulation. It is synthesized as a zymogen (pro-FD), but it is continuously converted to FD by circulating active MASP-3. FD is a unique, self-inhibited protease. It has an extremely low activity toward free factor B (FB), while it is a highly efficient enzyme toward FB complexed with C3b (C3bB). The structural basis of this phenomenon is known; however, the rate enhancement was not yet quantified. It has also been unknown whether pro-FD has any enzymatic activity. In this study, we aimed to measure the activity of human FD and pro-FD toward uncomplexed FB and C3bB in order to quantitatively characterize the substrate-induced activity enhancement and zymogenicity of FD. Pro-FD was stabilized in the proenzyme form by replacing Arg25 (precursor numbering) with Gln (pro-FD-R/Q). Activated MASP-1 and MASP-3 catalytic fragments were also included in the study for comparison. We found that the complex formation with C3b enhanced the cleavage rate of FB by FD approximately 20 million-fold. C3bB was also a better substrate for MASP-1, approximately 100-fold, than free FB, showing that binding to C3b renders the scissile Arg-Lys bond in FB to become more accessible for proteolysis. Though easily measurable, this cleavage by MASP-1 is not relevant physiologically. Our approach provides quantitative data for the two-step mechanism characterized by the enhanced susceptibility of FB for cleavage upon complex formation with C3b and the substrate-induced activity enhancement of FD upon its binding to C3bB. Earlier MASP-3 was also implicated as a potential FB activator; however, MASP-3 does not cleave C3bB (or FB) at an appreciable rate. Finally, pro-FD cleaves C3bB at a rate that could be physiologically significant. The zymogenicity of FD is approximately 800, i.e., the cleavage rate of C3bB by pro-FD-R/Q was found to be approximately 800-fold lower than that by FD. Moreover, pro-FD-R/Q at approximately 50-fold of the physiological FD concentration could restore half-maximal AP activity of FD-depleted human serum on zymosan. The observed zymogen activity of pro-FD might be relevant in MASP-3 deficiency cases or during therapeutic MASP-3 inhibition.

The complement system is the other major proteolytic cascade in the blood of vertebrates besides the coagulation–fibrinolytic system. Among the three main activation routes of complement, the lectin pathway (LP) has been discovered the latest, and it is still the subject of intense research. Mannose-binding lectin (MBL), other collectins, and ficolins are collectively termed as the pattern recognition molecules (PRMs) of the LP, and they are responsible for targeting LP activation to molecular patterns, e.g., on bacteria. MBL-associated serine proteases (MASPs) are the effectors, while MBL-associated proteins (MAps) have regulatory functions. Two serine protease components, MASP-1 and MASP-2, trigger the LP activation, while the third component, MASP-3, is involved in the function of the alternative pathway (AP) of complement. Besides their functions within the complement system, certain LP components have secondary (“moonlighting”) functions, e.g., in embryonic development. They also contribute to blood coagulation, and some might have tumor suppressing roles. Uncontrolled complement activation can contribute to the progression of many diseases (e.g., stroke, kidney diseases, thrombotic complications, and COVID-19). In most cases, the lectin pathway has also been implicated. In this review, we summarize the history of the lectin pathway, introduce their components, describe its activation and regulation, its roles within the complement cascade, its connections to blood coagulation, and its direct cellular effects. Special emphasis is placed on disease connections and the non-canonical functions of LP components.

The use of pesticides in agricultural practices raises concerns considering the toxic effects they generate in the environment; thus, their sustainable application in crop production remains a challenge. One of the frequently addressed issues regarding their application includes the development of a sustainable and ecofriendly approach for their degradation. Since the filamentous fungi can bioremediate various xenobiotics owing to their efficient and versatile enzymatic machinery, this review has addressed their performance in the biodegradation of organochlorine and organophosphorus pesticides. It is focused particularly on fungal strains belonging to the genera Aspergillus and Penicillium, since both are ubiquitous in the environment, and often abundant in soils contaminated with xenobiotics. Most of the recent reviews on microbial biodegradation of pesticides focus primarily on bacteria, and the soil filamentous fungi are mentioned only marginally there. Therefore, in this review, we have attempted to demonstrate and highlight the exceptional potential of aspergilli and penicillia in degrading the organochlorine and organophosphorus pesticides (e.g., endosulfan, lindane, chlorpyrifos, and methyl parathion). These biologically active xenobiotics have been degraded by fungi into various metabolites efficaciously, or these are completely mineralized within a few days. Since they have demonstrated high rates of degradation activity, as well as high tolerance to pesticides, most of the Aspergillus and Penicillium species strains listed in this review are excellent candidates for the remediation of pesticide-contaminated soils.

Manganese oxides are considered an essential component of natural geochemical barriers due to their redox and sorptive reactivity towards essential and potentially toxic trace elements. Despite the perception that they are in a relatively stable phase, microorganisms can actively alter the prevailing conditions in their microenvironment and initiate the dissolution of minerals, a process that is governed by various direct (enzymatic) or indirect mechanisms. Microorganisms are also capable of precipitating the bioavailable manganese ions via redox transformations into biogenic minerals, including manganese oxides (e.g., low-crystalline birnessite) or oxalates. Microbially mediated transformation influences the (bio)geochemistry of manganese and also the environmental chemistry of elements intimately associated with its oxides. Therefore, the biodeterioration of manganese-bearing phases and the subsequent biologically induced precipitation of new biogenic minerals may inevitably and severely impact the environment. This review highlights and discusses the role of microbially induced or catalyzed processes that affect the transformation of manganese oxides in the environment as relevant to the function of geochemical barriers.

The negative and cognitive symptoms of schizophrenia and related disorders may be due to reduced dopaminergic tone in cortical brain areas. Alteration in the function of dopamine (DA) D3 receptors may play a role in this cortical hypofunctionality and underlie the deficits in social behaviors and cognitive functions in schizophrenia. Cariprazine is a potent DA D3-preferring D3/D2 receptor partial agonist that is approved for the treatment of schizophrenia and bipolar disorder. The objective of the study was to compare the abilities of cariprazine, aripiprazole (another DA receptor partial agonist with more D2 receptor preference), and ABT-925 (a selective DA D3 antagonist) to counteract the social deficit and neurochemical alterations induced by the D3 receptor-preferring agonist (+)-PD 128907 (PD) in rats. Administration of PD (0.16 mg/kg; s.c.) induced a marked (−72%) but short-lasting disruption of the defensive social aggregation behavior (huddling) in the first 10-min period. Cariprazine at all doses (0.1, 0.3, 1 mg/kg; p.o.) almost completely abolished the PD-induced disruption of huddling. Likewise, ABT-925 (3 mg/kg; p.o.) and to a lesser extent aripiprazole (20 mg/kg; p.o.) were effective in blocking the PD-induced disruption of huddling. As measured by microdialysis, the highest dose of cariprazine prevented a PD-induced decrease in DA levels (40–80 min post PD dose) in the medial prefrontal cortex (mPFC), whereas aripiprazole did not have a significant effect. ABT-925 significantly counteracted the effect of PD at 80 min post-dose. In the nucleus accumbens (nAcc) shell, the highest dose of cariprazine, as well as ABT-925 and aripiprazole, significantly reversed the PD-induced decrease in DA levels. Taken together, these data provide behavioral and in vivo neurochemical evidence for the preferential DA D3 receptor action of cariprazine in the rat. This property of cariprazine may offer therapeutic benefits against the cognitive deficits and negative/depressive symptoms of schizophrenia and related disorders.

Iodine is an essential micronutrient for most of the living beings, including humans. Besides its indispensable role in animals, it also plays an important role in the environment. It undergoes several chemical and biological transformations resulting in the production of volatile methylated iodides, which play a key role in the iodine’s global geochemical cycle. Since it can also mitigate the process of climate change, it is reasonable to study its biogeochemistry. Therefore, the aim of this review is to provide information on its origin, global fluxes and mechanisms of production in the environment.

Biosorption is considered an effective technique for the treatment of heavy-metal-bearing wastewaters. In recent years, various biogenic products, including native and functionalized biopolymers, have been successfully employed in technologies aiming for the environmentally sustainable immobilization and removal of heavy metals at contaminated sites, including two commercially available heteropolysaccharides—xanthan and gellan. As biodegradable and non-toxic fermentation products, xanthan and gellan have been successfully tested in various remediation techniques. Here, to highlight their prospects as green adsorbents for water decontamination, we have reviewed their biosynthesis machinery and chemical properties that are linked to their sorptive interactions, as well as their actual performance in the remediation of heavy metal contaminated waters. Their sorptive performance in native and modified forms is promising; thus, both xanthan and gellan are emerging as new green-based materials for the cost-effective and efficient remediation of heavy metal-contaminated waters.

This work aimed to examine the bioleaching of manganese oxides at various oxidation states (MnO, MnO·Mn2O3, Mn2O3 and MnO2) by a strain of the filamentous fungus Aspergillus niger, a frequent soil representative. Our results showed that the fungus effectively disintegrated the crystal structure of selected mineral manganese phases. Thereby, during a 31-day static incubation of oxides in the presence of fungus, manganese was bioextracted into the culture medium and, in some cases, transformed into a new biogenic mineral. The latter resulted from the precipitation of extracted manganese with biogenic oxalate. The Mn(II,III)-oxide was the most susceptible to fungal biodeterioration, and up to 26% of the manganese content in oxide was extracted by the fungus into the medium. The detected variabilities in biogenic oxalate and gluconate accumulation in the medium are also discussed regarding the fungal sensitivity to manganese. These suggest an alternative pathway of manganese oxides’ biodeterioration via a reductive dissolution. There, the oxalate metabolites are consumed as the reductive agents. Our results highlight the significance of fungal activity in manganese mobilization and transformation. The soil fungi should be considered an important geoactive agent that affects the stability of natural geochemical barriers.

Bioleaching of mineral phases plays a crucial role in the mobility and availability of various elements, including selenium. Therefore, the leachability of selenium associated with the surfaces of ferric and manganese oxides and oxyhydroxides, the prevailing components of natural geochemical barriers, has been studied in the presence of filamentous fungus. Both geoactive phases were exposed to selenate and subsequently to growing fungus Aspergillus niger for three weeks. This common soil fungus has shown exceptional ability to alter the distribution and mobility of selenium in the presence of both solid phases. The fungus initiated the extensive bioextraction of selenium from the surfaces of amorphous ferric oxyhydroxides, while the hausmannite (Mn3O4) was highly susceptible to biodeterioration in the presence of selenium. This resulted in specific outcomes regarding the selenium, iron, and manganese uptake by fungus and residual selenium concentrations in mineral phases as well. The adverse effects of bioleaching on fungal growth are also discussed.

Synthesis of tetravalent thio- and selenogalactopyranoside-containing glycoclusters using azide-alkyne click strategy is presented. Prepared compounds are potential ligands of Pseudomonas aeruginosa lectin PA-IL. P. aeruginosa is an opportunistic human pathogen associated with cystic fibrosis, and PA-IL is one of its virulence factors. The interactions of PA-IL and tetravalent glycoconjugates were investigated using hemagglutination inhibition assay and compared with mono- and divalent galactosides (propargyl 1-thio- and 1-seleno-β-d-galactopyranoside, digalactosyl diselenide and digalactosyl disulfide). The lectin-carbohydrate interactions were also studied by saturation transfer difference NMR technique. Both thio- and seleno-tetravalent glycoconjugates were able to inhibit PA-IL significantly better than simple d-galactose or their intermediate compounds from the synthesis.

The aim of this work was to evaluate the transformation of manganese oxide (hausmannite) by microscopic filamentous fungus Aspergillus niger and the effects of the transformation on mobility and bioavailability of arsenic. Our results showed that the A. niger strain CBS 140837 greatly affected the stability of hausmannite and induced its transformation into biogenic crystals of manganese oxalates—falottaite and lindbergite. The transformation was enabled by fungal acidolysis of hausmannite and subsequent release of manganese ions into the culture medium. While almost 45% of manganese was bioextracted, the arsenic content in manganese precipitates increased throughout the 25-day static cultivation of fungus. This significantly decreased the bioavailability of arsenic for the fungus. These results highlight the unique A. niger strain’s ability to act as an active geochemical factor via its ability to acidify its environment and to induce formation of biogenic minerals. This affects not only the manganese speciation, but also bioaccumulation of potentially toxic metals and metalloids associated with manganese oxides, including arsenic.

Copyright of Military Engineer / Hadmérnök is the property of National University of Public Service and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Military Engineer / Hadmérnök is the property of National University of Public Service and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Different spatial metaphors to describe the differences of global economy have been widely used in much research connected to the issues of global inequalities and globalization itself. Since the emergence of the term "Third World" as one of the abovementioned metaphors, its meaning and its geographical reference have been ambiguous and the term itself has faced many controversies and criticisms. Generally, the term has always had both a political and a socioeconomic meaning, however, at first - and primarily during the Cold War - its political sense was mainly applied. The main aim of our paper is to give a brief overview of the concept "Third World," using in particular the literature linked strictly to the problems and contradictions associated with it. First, I review the geopolitical situation in which the notion appeared, focusing on the development discourse of the Cold War era. Then the different explanations, and later the main controversies linked to the concept, will be discussed. I argue and try to confirm that the notion is closely related to postwar geopolitics and the changing scientific approaches to the discourse on development. [ABSTRACT FROM AUTHOR]

Human Galectin-3 (hGal-3) is a protein that selectively binds to β-galactosides and holds diverse roles in both normal and pathological circumstances. Therefore, targeting hGal-3 has become a vibrant area of research in the pharmaceutical chemistry. As a step towards the development of novel hGal-3 inhibitors, we synthesized and investigated derivatives of thiodigalactoside (TDG) modified with different aromatic substituents. Specifically, we describe a high-yielding synthetic route of thiodigalactoside (TDG); an optimized procedure for the synthesis of the novel 3,3′-di-O-(quinoline-2-yl)methyl)-TDG and three other known, symmetric 3,3′-di-O-TDG derivatives ((naphthalene-2yl)methyl, benzyl, (7-methoxy-2H-1-benzopyran-2-on-4-yl)methyl). In the present study, using competition Saturation Transfer Difference (STD) NMR spectroscopy, we determined the dissociation constant (Kd) of the former three TDG derivatives produced to characterize the strength of the interaction with the target protein (hGal-3). Based on the Kd values determined, the (naphthalen-2-yl)methyl, the (quinolin-2-yl)methyl and the benzyl derivatives bind to hGal-3 94, 30 and 24 times more strongly than TDG. Then, we studied the binding modes of the derivatives in silico by molecular docking calculations. Docking poses similar to the canonical binding modes of well-known hGal-3 inhibitors have been found. However, additional binding forces, cation–π interactions between the arginine residues in the binding pocket of the protein and the aromatic groups of the ligands, have been established as significant features. Our results offer a molecular-level understanding of the varying affinities observed among the synthesized thiodigalactoside derivatives, which can be a key aspect in the future development of more effective ligands of hGal-3.

The Gram-negative bacterium Pseudomonas aeruginosa is an important opportunistic human pathogen associated with cystic fibrosis. P. aeruginosa produces two soluble lectins, the d-galactose-specific lectin PA-IL (LecA) and the l-fucose-specific lectin PA-IIL (LecB), among other virulence factors. These lectins play an important role in the adhesion to host cells and biofilm formation. Moreover, PA-IL is cytotoxic to respiratory cells in the primary culture. Therefore, these lectins are promising therapeutic targets. Specifically, carbohydrate-based compounds could inhibit their activity. In the present work, a 3-O-fucosyl lactose-containing tetravalent glycocluster was synthesized and utilized as a mutual ligand of galactophilic and fucophilic lectins. Pentaerythritol equipped with azido ethylene glycol-linkers was chosen as a multivalent scaffold and the glycocluster was constructed by coupling the scaffold with propargyl 3-O-fucosyl lactoside using an azide-alkyne 1,3-dipolar cycloaddition reaction. The interactions between the glycocluster and PA-IL or PA-IIL were investigated by isothermal titration microcalorimetry and saturation transfer difference NMR spectroscopy. These results may assist in the development of efficient anti-adhesion therapy for the treatment of a P. aeruginosa infection.