Molecular Determinants of Juvenile Hormone Action as Revealed by 3D QSAR Analysis in Drosophila

BACKGROUND:Postembryonic development, including metamorphosis, of many animals is under control of hormones. In Drosophila and other insects these developmental transitions are regulated by the coordinate action of two principal hormones, the steroid ecdysone and the sesquiterpenoid juvenile hormone (JH). While the mode of ecdysone action is relatively well understood, the molecular mode of JH action remains elusive. METHODOLOGY/PRINCIPAL FINDINGS:To gain more insights into the molecular mechanism of JH action, we have tested the biological activity of 86 structurally diverse JH agonists in Drosophila melanogaster. The results were evaluated using 3D QSAR analyses involving CoMFA and CoMSIA procedures. Using this approach we have generated both computer-aided and species-specific pharmacophore fingerprints of JH and its agonists, which revealed that the most active compounds must possess an electronegative atom (oxygen or nitrogen) at both ends of the molecule. When either of these electronegative atoms are replaced by carbon or the distance between them is shorter than 11.5 A or longer than 13.5 A, their biological activity is dramatically decreased. The presence of an electron-deficient moiety in the middle of the JH agonist is also essential for high activity. CONCLUSIONS/SIGNIFICANCE:The information from 3D QSAR provides guidelines and mechanistic scope for identification of steric and electrostatic properties as well as donor and acceptor hydrogen-bonding that are important features of the ligand-binding cavity of a JH target protein. In order to refine the pharmacophore analysis and evaluate the outcomes of the CoMFA and CoMSIA study we used pseudoreceptor modeling software PrGen to generate a putative binding site surrogate that is composed of eight amino acid residues corresponding to the defined molecular interactions

Fine structure of Drosophila larval salivary gland ducts as revealed by laser confocal microscopy and SEM

The functions of the larval salivary glands (SGs) of Drosophila are traditionally associated with the production of a massive secretion during puparium formation; it is exocytosed into a centrally located lumen and subsequently expectorated via ducts, the pharynx and mouth. This so-called proteinaceous glue serves as an adhesive to attach the puparial case to a solid substrate. Great attention has been paid to the secretory cells of SGs, which are famous for their giant polytene chromosomes. However, substantially less attention has been devoted to individual or common ducts that form the most proximal portion of the SG organ via which the glue is released into the pharynx. In the present paper, we describe the organization and fine structure of the taenidia, highly specialized circumferential ring-like extracellular (cuticular) components on the internal side of these tubes. Two chitin-specific probes that have previously been used to recognize taenidia in Drosophila tracheae, Calcofluor White M2R (also known as Fluorescent Brightener 28) and the novel vital fluorescent dye SiR-COOH, show positively stained ductal taenidia in late larval SGs. As seen using scanning electron microscopy (SEM), the interior of the ductal tube contains regular and densely-arranged ridge-like circumferential rings which represent local thickenings of the cuticle in various geometries. The microtubular arrays that optically colocalize with taenidia in both the trachea and SG ducts are specifically and strongly recognized by fluorescently-conjugated colchicine as well as anti-tubulin antibody. In contrast to taenidia in the tracheae, the analogous structures in SG ducts cannot be detected by fluorescently-labeled phalloidin or even actin-GFP fusion protein, suggesting that the ducts lack a cortical network made of filamentous actin. We speculate that these taenidia may serve to reinforce the duct during the secretory processes that SGs undergo during late larval and late prepupal stages

REMLABNET - Solar system, new virtual laboratory with mathematical model using vector functions for primary, secondary and high schools and universities

The main role of this article is to create a mathematical model using virtual laboratories for primary, secondary and high schools, and universities. The aim of the article is such a mathematical model to be applicable at all levels of education, with a substantial idea to teach students to think more scientifically. Analysis showed us two possible methods of creating a given model. Possible implementation is with differential equations or vector functions. After a thorough consideration and analysis of the subject we chose a vector function that interfere with a larger spectrum of students compared to differential equations. The main contribution of the work is already mentioned and that is a virtual laboratory, which in our case describes the Solar system and its movement using vector functions. This laboratory is useful, from a primary school, where students are getting to know the Solar system to secondary and high schools, and colleges, where educators can use this model on physics and mathematics lessons when taking over teaching vectors.Trnava University in Trnava [12/TU/2021

REMLABNET – Solar System, New Virtual Laboratory with Mathematical Model Using Vector Functions for Primary, Secondary and High Schools and Universities

The main role of this article is to create a mathematical model using virtual laboratories for primary, secondary and high schools, and universities. The aim of the article is such a mathematical model to be applicable at all levels of education, with a substantial idea to teach students to think more scientifically. Analysis showed us two possible methods of creating a given model. Possible implementation is with differential equations or vector functions. After a thorough consideration and analysis of the subject we chose a vector function that interfere with a larger spectrum of students compared to differential equations. The main contribution of the work is already mentioned and that is a virtual laboratory, which in our case describes the Solar system and its movement using vector functions. This laboratory is useful, from a primary school, where students are getting to know the Solar system to secondary and high schools, and colleges, where educators can use this model on physics and mathematics lessons when taking over teaching vectors

Experimental Study of the Bending Behaviour of the Neovius Porous Structure Made Additively from Aluminium Alloy

Porous materials bring components not only direct advantages in the form of lightening of constructions, saving of production materials, or improvement of physical properties, but also secondary advantages, which are manifested as a result of their daily use, e.g., in aviation and the automotive industry, which is manifested in saving fuel and, thus, environmental protection. The aim of this article is to examine the influence of the volume ratio of a complex porous structure, the so-called Neovius, on bending properties. Samples with five different relative weights of 15, 20, 25, 30, and 50% (±1%) were fabricated from AlSi10Mg aluminum alloy by Direct Laser Metal Sintering (DLMS) technology. A three-point bending test until specimen failure was performed at ambient temperature on a Zwick/Roell 1456 universal testing machine. The dependences of the bending forces on the deflection were recorded. The maximum stresses, energy absorption, and ductility indexes were calculated to compare the bending behavior of beams filled with this type of complex cellular structure. The results showed that Neovius, with a relative weight of 50%, was much more brittle compared to the other samples, while the Neovius structure, with a relative weight of 30%, appeared to be the most suitable structure for bent components among those tested. This study is a contribution not only to the development of the space and aviation industry but also to the expansion of the knowledge base in the field of material sciences. This know-how can also provide a basis for defining boundary conditions in the simulation of behavior and numerical analyses of 3D-printed lightweight components

Experimental study of the bending behaviour of the neovius porous structure made additively from aluminium alloy

Porous materials bring components not only direct advantages in the form of lightening of constructions, saving of production materials, or improvement of physical properties, but also secondary advantages, which are manifested as a result of their daily use, e.g., in aviation and the automotive industry, which is manifested in saving fuel and, thus, environmental protection. The aim of this article is to examine the influence of the volume ratio of a complex porous structure, the so-called Neovius, on bending properties. Samples with five different relative weights of 15, 20, 25, 30, and 50% (+/- 1%) were fabricated from AlSi10Mg aluminum alloy by Direct Laser Metal Sintering (DLMS) technology. A three-point bending test until specimen failure was performed at ambient temperature on a Zwick/Roell 1456 universal testing machine. The dependences of the bending forces on the deflection were recorded. The maximum stresses, energy absorption, and ductility indexes were calculated to compare the bending behavior of beams filled with this type of complex cellular structure. The results showed that Neovius, with a relative weight of 50%, was much more brittle compared to the other samples, while the Neovius structure, with a relative weight of 30%, appeared to be the most suitable structure for bent components among those tested. This study is a contribution not only to the development of the space and aviation industry but also to the expansion of the knowledge base in the field of material sciences. This know-how can also provide a basis for defining boundary conditions in the simulation of behavior and numerical analyses of 3D-printed lightweight components.Ministry of Education, MOE; Ministerstvo školstva, vedy, výskumu a športu Slovenskej republiky: APVV-19-0550; Kultúrna a Edukacná Grantová Agentúra MŠVVaŠ SR, KEGA: 005TUKE-4/2021, 032TUKE-4/2022, SK-CN-21-0046Ministry of education, science, research and sport of the Slovak Republic [APVV-19-0550, KEGA 005TUKE-4/2021]; [KEGA 032TUKE-4/2022]; [SK-CN-21-0046

Investigation of the influence of orientation on the tensile properties of 3D printed samples with gyroid structure

The article deals with experimental testing of a complex shape porous structure called Gyroid with a specific volume ratio Vr = 30 %. The main goal was to investigate the effect of orientation and location of samples on their resulting mechanical tensile properties. All samples were made of ABS-T silver material by 3D printing. Virtual sample models were designed using two different CAD software. Tensile samples were produced in two different directions perpendicular to each other. Five samples were made horizontally, so the vector of the loading tensile force lay in the plane of the printed layer. The other five samples were made vertically, so the sample was loaded perpendicular to the plane of the printed layer. Experimental testing and statistical processing have shown the orientation and direction of the printed layer. Experimental testing and statistical processing have shown that the orientation and direction of 3D printing have a significant impact on the resulting mechanical properties and quality of a component, as well as on the time of the 3D printing process itself. © 2022 IEEE

Zn–0.8Mg–0.2Sr (wt.%) Absorbable Screws—An In-Vivo Biocompatibility and Degradation Pilot Study on a Rabbit Model

In this pilot study, we investigated the biocompatibility and degradation rate of an extruded Zn–0.8Mg–0.2Sr (wt.%) alloy on a rabbit model. An alloy screw was implanted into one of the tibiae of New Zealand White rabbits. After 120 days, the animals were euthanized. Evaluation included clinical assessment, microCT, histological examination of implants, analyses of the adjacent bone, and assessment of zinc, magnesium, and strontium in vital organs (liver, kidneys, brain). The bone sections with the implanted screw were examined via scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS). This method showed that the implant was covered by a thin layer of phosphate-based solid corrosion products with a thickness ranging between 4 and 5 µm. Only negligible changes of the implant volume and area were observed. The degradation was not connected with gas evolution. The screws were fibrointegrated, partially osseointegrated histologically. We observed no inflammatory reaction or bone resorption. Periosteal apposition and formation of new bone with a regular structure were frequently observed near the implant surface. The histological evaluation of the liver, kidneys, and brain showed no toxic changes. The levels of Zn, Mg, and Sr after 120 days in the liver, kidneys, and brain did not exceed the reference values for these elements. The alloy was safe, biocompatible, and well-tolerated

A Complex Evaluation of the In-Vivo Biocompatibility and Degradation of an Extruded ZnMgSr Absorbable Alloy Implanted into Rabbit Bones for 360 Days

The increasing incidence of trauma in medicine brings with it new demands on the materials used for the surgical treatment of bone fractures. Titanium, its alloys, and steel are used worldwide in the treatment of skeletal injuries. These metallic materials, although inert, are often removed after the injured bone has healed. The second-stage procedure—the removal of the plates and screws—can overwhelm patients and overload healthcare systems. The development of suitable absorbable metallic materials would help us to overcome these issues. In this experimental study, we analyzed an extruded Zn-0.8Mg-0.2Sr (wt.%) alloy on a rabbit model. From this alloy we developed screws which were implanted into the rabbit tibia. After 120, 240, and 360 days, we tested the toxicity at the site of implantation and also within the vital organs: the liver, kidneys, and brain. The results were compared with a control group, implanted with a Ti-based screw and sacrificed after 360 days. The samples were analyzed using X-ray, micro-CT, and a scanning electron microscope. Chemical analysis revealed only small concentrations of zinc, strontium, and magnesium in the liver, kidneys, and brain. Histologically, the alloy was verified to possess very good biocompatibility after 360 days, without any signs of toxicity at the site of implantation. We did not observe raised levels of Sr, Zn, or Mg in any of the vital organs when compared with the Ti group at 360 days. The material was found to slowly degrade in vivo, forming solid corrosion products on its surface