TusA influences Fe-S cluster assembly and iron homeostasis in E. coli by reducing the translation efficiency of Fur.

All sulfur transfer pathways have generally a l-cysteine desulfurase as an initial sulfur-mobilizing enzyme in common, which serves as a sulfur donor for the biosynthesis of numerous sulfur-containing biomolecules in the cell. In Escherichia coli, the housekeeping l-cysteine desulfurase IscS has several interaction partners, which bind at different sites of the protein. So far, the interaction sites of IscU, Fdx, CyaY, and IscX involved in iron-sulfur (Fe-S) cluster assembly have been mapped, in addition to TusA, which is required for molybdenum cofactor biosynthesis and mnm5s2U34 tRNA modifications, and ThiI, which is involved in thiamine biosynthesis and s4U8 tRNA modifications. Previous studies predicted that the sulfur acceptor proteins bind to IscS one at a time. E. coli TusA has, however, been suggested to be involved in Fe-S cluster assembly, as fewer Fe-S clusters were detected in a ∆tusA mutant. The basis for this reduction in Fe-S cluster content is unknown. In this work, we investigated the role of TusA in iron-sulfur cluster assembly and iron homeostasis. We show that the absence of TusA reduces the translation of fur, thereby leading to pleiotropic cellular effects, which we dissect in detail in this study.IMPORTANCEIron-sulfur clusters are evolutionarily ancient prosthetic groups. The ferric uptake regulator plays a major role in controlling the expression of iron homeostasis genes in bacteria. We show that a ∆tusA mutant is impaired in the assembly of Fe-S clusters and accumulates iron. TusA, therefore, reduces fur mRNA translation leading to pleiotropic cellular effects.

Effect of saccharin, a non-nutritive sweeteners, on insulin and blood glucose levels in healthy young men: A crossover trial.

BACKGROUND AND AIMS: Artificial sweeteners used instead of sugar were considered as the best alternatives that have no endocrine effects. However, it has recently been suggested that artificial sweeteners may cause impaired metabolic parameters. The hypothesis of the study was there is an association between acute saccharin consumption and both glycemia and insulin response in young healthy adult men. METHODS: 9 healthy adult males were included in this study. This study randomly provided participants with preloads as (a)300 ml of water, or 300 ml of water sweetened with (b)75 g of sucrose, (c)240 mg of saccharine (adjusted to the sweetness of 75 g of sucrose) 1 h before a standard breakfast. RESULTS: Compared to mean blood glucose and serum insulin after test drinks consumption, there was only one difference between sucrose and saccharin trials in the 15th minute (117.0 ± 18.70, 95.4 ± 5.64 mg/dl respectively, p < 0.05). At the 60th minute, insulin secretion (0.80 ± 0.27 pg/dl) after the sucrose trial was found significantly higher than the saccharin trial (0.53 ± 0.09 pg/dl) and water (0.49 ± 0.06 pg/dl) (p < 0.05). Although at all intervals (except 90th minute), the mean insulin is higher after the saccharin trial compared to the water trial, these were non-statistically significant differences (p > 0.05). CONCLUSIONS: Consequently, it was determined that saccharin had no glycemic effect. However, for the effect on serum insulin to be clarified, the long-term effects should be investigated.

Use of Dorsal Nasal Flap in Combination With Nasolabial Perforator Propeller Flap for Reconstruction of Nasal Skin Defects of Medium to Large Size; A Simpler Alternative to Frontal Flap.

ABSTRACT: Nasal reconstruction is one of the most challenging procedures in plastic surgery. To get optimal aesthetic and functional results, the surgeon should know all the options well. Forehead flap is the gold standard technique for closure of medium to large defects of the nose. Although it provides a very good color and texture match, it may become a difficult option in patients with poor condition. The aim of this study was to define a simpler technique for nasal reconstruction using combined local flaps.Twelve patients, operated using a dorsal nasal flap combined with a nasolabial perforator propeller flap, were presented in the study. Properties of the patients, defect size and locations, and complications were evaluated.The mean size of the reconstructed defects was 10.1 cm2. No flap loss was observed. Venous congestion was the most common complication and resolved spontaneously in all cases. Two cases had partial distal necrosis, which also healed spontaneously.Closure was achieved successfully in all cases with a medium to large nasal defect using a combined dorsal nasal flap and nasolabial perforator propeller flap. This method can be used as an alternative to forehead flap.

TusA Is a Versatile Protein That Links Translation Efficiency to Cell Division in Escherichia coli.

To enable accurate and efficient translation, sulfur modifications are introduced posttranscriptionally into nucleosides in tRNAs. The biosynthesis of tRNA sulfur modifications involves unique sulfur trafficking systems for the incorporation of sulfur atoms in different nucleosides of tRNA. One of the proteins that is involved in inserting the sulfur for 5-methylaminomethyl-2-thiouridine (mnm5s2U34) modifications in tRNAs is the TusA protein. TusA, however, is a versatile protein that is also involved in numerous other cellular pathways. Despite its role as a sulfur transfer protein for the 2-thiouridine formation in tRNA, a fundamental role of TusA in the general physiology of Escherichia coli has also been discovered. Poor viability, a defect in cell division, and a filamentous cell morphology have been described previously for tusA-deficient cells. In this report, we aimed to dissect the role of TusA for cell viability. We were able to show that the lack of the thiolation status of wobble uridine (U34) nucleotides present on Lys, Gln, or Glu in tRNAs has a major consequence on the translation efficiency of proteins; among the affected targets are the proteins RpoS and Fis. Both proteins are major regulatory factors, and the deregulation of their abundance consequently has a major effect on the cellular regulatory network, with one consequence being a defect in cell division by regulating the FtsZ ring formation.IMPORTANCE More than 100 different modifications are found in RNAs. One of these modifications is the mnm5s2U modification at the wobble position 34 of tRNAs for Lys, Gln, and Glu. The functional significance of U34 modifications is substantial since it restricts the conformational flexibility of the anticodon, thus providing translational fidelity. We show that in an Escherichia coli TusA mutant strain, involved in sulfur transfer for the mnm5s2U34 thio modifications, the translation efficiency of RpoS and Fis, two major cellular regulatory proteins, is altered. Therefore, in addition to the transcriptional regulation and the factors that influence protein stability, tRNA modifications that ensure the translational efficiency provide an additional crucial regulatory factor for protein synthesis.

Anthropometric breast measurements of young women with no history of pregnancy or surgery in Turkey.

Anthropometric measurements of the breast play a guiding role in surgical planning. In our study, it was aimed to determine the normal shape and size of the breast by taking measurements in young women who did not experience pregnancy or surgery and comparing them with the results of other studies. The breast parameters of 88 women aged between 18 to 30 years old, with a normal body mass index, with no history of previous pregnancy, surgery or rapid weight gain were measured. The measured parameters were age, body mass index, cup size, distance between nipple and suprasternal notch, distance between both nipples, distance between midclavicular point and nipple, distance between midclavicular point and upper border of the breast, the distance between the midaxillary line and nipple, the distance between the nipple and inframammarian fold, the projection of the breast, the projection of the nipple and the chest circumference under the breast. The mean values ​​were determined and the correlation between the parameters was evaluated statistically. A significant correlation was found between cup size and all parameters except for the chest circumference and nipple projection. The distance between the midclavicular point and upper border of the breast was found correlated with the cup size. In addition, a significant correlation was found between body mass index and all other parameters. This study revealed the average breast size and measurements of women in Turkey. It can be useful to guide for both reconstructive and aesthetic procedures of the breast.

Induction of immunogenic cell death of cancer cells through nanoparticle-mediated dual chemotherapy and photothermal therapy.

The use of nanomedicines to induce immunogenic cell death is a new strategy that aims to increase tumor immunogenicity and thereby prime tumors for further immunotherapies. In this study, we developed a nanoparticle formulation for combinatory chemotherapy and photothermal therapy based only on materials previously used in FDA-approved products and investigated the effect of the combinatory therapy on the growth inhibition and induction of immunogenic cell death in human MDA-MB-231 breast cancer cells. The formulation consists of ~108-nm nanoparticles made of poly(lactic acid)-b-methoxy poly(ethylene glycol) which carry doxorubicin for chemotherapy and indocyanine green for photothermal therapy. A 0.3 mg/mL suspension of NPs increased the medium temperature up to 10 °C upon irradiation with an 808-nm diode laser. In vitro studies showed that combination of laser assisted indocyanine green-mediated photothermal therapy and doxorubicin-mediated chemotherapy effectively eradicated cancer cells and resulted in the highest level of damage-associated molecular pattern presentation (calreticulin, high mobility group box 1, and adenosine triphosphate) compared to the individual treatments alone. These results demonstrate that our nanoparticle-mediated combinatory approach led to the most intense immunogenic cell death when compared to individual chemotherapy or photothermal therapy, making it a potent option for future in vivo studies in combination with cancer immunotherapies.

Senior high school students' opinions on the nursing profession: A ten-year comparative study.

AIMS: To analyse the changes in senior students' opinions about the nursing profession over a 10-year period. DESIGN: A descriptive and comparative study. METHOD: Data were collected using a questionnaire form, which was completed by 400 senior high school students in Çankiri city center during 2007-2008 (Group 1) and 2017-2018 (Group 2) academic years. RESULTS: Compared with 10 years ago, more students referred to nurses as 'knowledgeable, concerned, and tolerant'. There were fewer students who knew the duties of nurses. There were significantly fewer students who wanted to be nurses and many who wanted to be nurses in both groups said it was 'because they love nursing'. Compared with 10 years ago, more students said they wanted to be nurses because their parents wanted them to be nurses, but fewer students said they wanted to be nurses because they love people. There were more students who did not want to be nurses 'because it is tiring and entails irregular work hours'. However, more students said that they would like to go into nursing if the salary was satisfactory. CONCLUSION: The study showed that, compared with 10 years ago, more students defined nurses as knowledgeable and professional. They reported they did not currently wish to enter the nursing profession, but that they would do so if the wages were high. IMPACT: This study aims to determine the change in young individuals' opinions about the nursing profession in Turkey over a 10-year period. Due to poor work conditions in the nursing profession, most of the students did not want to be nurses, but their opinions might change if nurses' salaries were satisfactory. Academicians and nurses play an important role in introducing the nursing profession to students when they choose their career and informing high school teachers, who advise these students.

Photo-Uncaging of a Microtubule-Targeted Rigidin Analogue in Hypoxic Cancer Cells and in a Xenograft Mouse Model.

Marine alkaloid rigidins are cytotoxic compounds known to kill cancer cells at nanomolar concentrations by targeting the microtubule network. Here, a rigidin analogue containing a thioether group was "caged" by coordination of its thioether group to a photosensitive ruthenium complex. In the dark, the coordinated ruthenium fragment prevented the rigidin analogue from inhibiting tubulin polymerization and reduced its toxicity in 2D cancer cell line monolayers, 3D lung cancer tumor spheroids (A549), and a lung cancer tumor xenograft (A549) in nude mice. Photochemical activation of the prodrug upon green light irradiation led to the photosubstitution of the thioether ligand by water, thereby releasing the free rigidin analogue capable of inhibiting the polymerization of tubulin. In cancer cells, such photorelease was accompanied by a drastic reduction of cell growth, not only when the cells were grown in normoxia (21% O2) but also remarkably in hypoxic conditions (1% O2). In vivo, low toxicity was observed at a dose of 1 mg·kg-1 when the compound was injected intraperitoneally, and light activation of the compound in the tumor led to 30% tumor volume reduction, which represents the first demonstration of the safety and efficacy of ruthenium-based photoactivated chemotherapy compounds in a tumor xenograft.

Microtubule-Targeting 7-Deazahypoxanthines Derived from Marine Alkaloid Rigidins: Exploration of the N3 and N9 Positions and Interaction with Multidrug-Resistance Proteins.

Our laboratories have been investigating synthetic analogues of marine alkaloid rigidins that possess promising anticancer activities. These analogues, based on the 7-deazahypoxanthine skeleton, are available in one- or two-step synthetic sequences and exert cytotoxicity by disrupting microtubule dynamics in cancer cells. In the present work we extended the available structure-activity relationship (SAR) data to N3- and N9-substituted derivatives. Although N3 substitution results in loss of activity, the N9-substituted compounds retain nanomolar antiproliferative activities and the anti-tubulin mode of action of the original unsubstituted compounds. Furthermore, our results also demonstrate that multidrug-resistance (MDR) proteins do not confer resistance to both N9-unsubstituted and -substituted compounds. It was found that sublines overexpressing ABCG2, ABCC1, and ABCB1 proteins are as responsive to the rigidin analogues as their parental cell lines. Thus, the study reported herein provides further impetus to investigate the rigidin-inspired 7-deazahypoxanthines as promising anticancer agents.

Doxorubicin-loaded protease-activated near-infrared fluorescent polymeric nanoparticles for imaging and therapy of cancer.

INTRODUCTION: Despite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses. MATERIAL AND METHODS: In this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer. These core-shell nanoparticles were prepared by nanoprecipitation of blends of the biodegradable and biocompatible amphiphilic copolymers poly(lactic-co-glycolic acid)-b-poly-l-lysine and poly(lactic acid)-b-poly(ethylene glycol). Poly-l-lysine in the first copolymer was covalently decorated with near-infrared fluorescent Alexa Fluor 750 molecules. RESULTS: The spherical nanoparticles had an average size of 60-80 nm. The chemotherapeutic drug doxorubicin was encapsulated in the core of nanoparticles at a loading of 3% (w:w) and controllably released over a period of 30 days. A 33-fold increase in near-infrared fluorescence, mediated by protease-mediated cleavage of the Alexa Fluor 750-labeled poly-l-lysine on the surface of the nanoparticles, was observed upon interaction with the model protease trypsin. The cytocompatibility of drug-free nanoparticles and growth inhibition of drug-loaded nanoparticles on MDA-MB-231 breast cancer cells were investigated with a luminescence cell-viability assay. Drug-free nanoparticles were found to cause minimal toxicity, even at high concentrations (0.2-2,000 µg/mL), while doxorubicin-loaded nanoparticles significantly reduced cell viability at drug concentrations >10 µM. Finally, the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy, demonstrating the potential of the nanoparticles to act as near-infrared fluorescence optical imaging agents and drug-delivery carriers. CONCLUSION: Doxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were prepared successfully by nanoprecipitation of copolymer blends. These nanoparticles were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells.

Investigation of photocatalytic effect of SnO2 nanoparticles synthesized by hydrothermal method on the decolorization of two organic dyes.

Tin oxide nanoparticles about 4 nm in size were successfully synthesized using hydrothermal method. The photocatalytic activity of the particles was determined by the decolorization of malachite green (MG) and titanium yellow (TY) under UV light. 12 ppm of MG and TY were used for the solution with an initial volume of 100 mL. The amounts of catalysts were 10, 30 and 50 mg. The effect of the catalyst loading on the reaction kinetic parameters and the decolorization rate constants (k) were determined. In order to reveal the photocatalytic efficiency of the nano particles, further experiments were conducted with bulk SnO(2). The oxygen species registered no observable effect on the reaction mechanism as nitrogen bubbling leads to no change in decolorization rates. Results showed that the synthesized nano tin oxide particles represent excellent photocatalytic activity for the decolorization of 12 ppm MG under UV light with 150 min of irradiation time. The energies of the highest occupied molecular orbital (HOMO) E(HOMO) of the dyes were also calculated by using the quantum chemical software in order to discuss the differences for the decolorization of two dyes. Electrical energy efficiency values for the decolorization of two dyes were also calculated.