The molecular basis of conformational instability of the ecdysone receptor DNA binding domain studied by in silico and in vitro experiments

The heterodimer of the ecdysone receptor (EcR) and ultraspiracle (Usp), members of the nuclear receptors superfamily, regulates gene expression associated with molting and metamorphosis in insects. The DNA binding domains (DBDs) of the Usp and EcR play an important role in their DNA-dependent heterodimerization. Analysis of the crystal structure of the UspDBD/EcRDBD heterocomplex from Drosophila melanogaster on the hsp27 gene response element, suggested an appreciable similarity between both DBDs. However, the chemical denaturation experiments showed a categorically lower stability for the EcRDBD in contrast to the UspDBD. The aim of our study was an elucidation of the molecular basis of this intriguing instability. Toward this end, we mapped the EcRDBD amino acid sequence positions which have an impact on the stability of the EcRDBD. The computational protein design and in vitro analyses of the EcRDBD mutants indicate that non-conserved residues within the α-helix 2, forming the EcRDBD hydrophobic core, represent a specific structural element that contributes to instability. In particular, the L58 appears to be a key residue which differentiates the hydrophobic cores of UspDBD and EcRDBD and is the main reason for the low stability of the EcRDBD. Our results might serve as a benchmark for further studies of the intricate nature of the EcR molecule

Rak pęcherzykowy tarczycy z przerzutami do wątroby — diagnostyka, leczenie i prognoza

  Follicular thyroid carcinoma (FTC) is the second most common type of thyroid cancer (TC) and accounts for approximately 10% of all TC cases. Liver metastases are a rare presentation in 0.5–1% of follicular thyroid cancers, usually occurring in the setting of widely disseminated FTC disease, and their presence is associated with poor prognosis. Until now, there have been only 30 cases of FTC liver metastases described in the literature. Herein, we review publications and describe diagnostic tools that may be used in the diagnosis and follow-up of FTC metastases to the liver, including biopsy and imaging techniques like US, CT, MRI, SPECT, PET, and radioiodine scintigraphy. We also present and discuss current methods of treatment, e.g. TSH suppressive therapy with levothyroxine, surgery, radiofrequency ablation (RFA), transarterial embolisation (TAE), liver transarterial chemoembolisation (TACE), chemotherapy with cisplatin and doxorubicin, treatment with Indium- 111-octreotide (or its analogues), and tyrosine kinase inhibitors (sorafenib, sunitinib). At the end we describe the course, results of diagnostics, and treatment in a patient with large multiple FTC metastases to the liver. (Endokrynol Pol 2016; 67 (3): 332–347)    Rak pęcherzykowy tarczycy (FTC) jest drugim najczęstszym typem raka tarczycy (TC) i stanowi około 10% wszystkich TC. Przerzuty do wątroby występują w 0,5–1% przypadków FTC, zwykle w przypadku znacznie zaawansowanej choroby nowotworowej i wiążą się ze złą prognozą. Do tej pory, tylko 30 przypadków FTC z przerzutami do wątroby zostało opisanych w literaturze. W niniejszej pracy dokonano przeglądu literatury i opisu metod diagnostycznych jakie mogą być użyte w badaniu i kontroli przerzutów FTC do wątroby, w tym biopsji, technik obrazowych, takich jak: USG, KT, MRI, SPECT, PET i scyntygrafii jodowej. Zaprezentowano i omówiono aktualne metody leczenia: terapię L-tyroksyną w dawce supresyjnej, leczenie operacyjne, ablację prądem o częstotliwości fal radiowych (RFA), embolizację przeztętniczą (TAE), przeztętniczą chemoembolizację, chemioterapię z użyciem cisplatyny i doksyrubicyny, leczenie z użyciem analogów somatostatyny w tym octreotydu znakowanego izotopem indu 111In, czy terapię z użyciem inhibitorów kinazy tyrozynowej (sorafenib, sunitynib). Na końcu opisano przebieg choroby, wyniki badań diagnostycznych i podjęte leczenie u chorej z ogromnymi mnogimi przerzutami FTC do wątroby. (Endokrynol Pol 2016; 67 (3): 332–347)

The role of tannic acid and sodium citrate in the synthesis of silver nanoparticles

We describe herein the significance of a sodium citrate and tannic acid mixture in the synthesis of spherical silver nanoparticles (AgNPs). Monodisperse AgNPs were synthesized via reduction of silver nitrate using a mixture of two chemical agents: sodium citrate and tannic acid. The shape, size and size distribution of silver particles were determined by UV–Vis spectroscopy, dynamic light scattering (DLS) and scanning transmission electron microscopy (STEM). Special attention is given to understanding and experimentally confirming the exact role of the reagents (sodium citrate and tannic acid present in the reaction mixture) in AgNP synthesis. The oxidation and reduction potentials of silver, tannic acid and sodium citrate in their mixtures were determined using cyclic voltammetry. Possible structures of tannic acid and its adducts with citric acid were investigated in aqueous solution by performing computer simulations in conjunction with the semi-empirical PM7 method. The lowest energy structures found from the preliminary conformational search are shown, and the strength of the interaction between the two molecules was calculated. The compounds present on the surface of the AgNPs were identified using FT-IR spectroscopy, and the results are compared with the IR spectrum of tannic acid theoretically calculated using PM6 and PM7 methods. The obtained results clearly indicate that the combined use of sodium citrate and tannic acid produces monodisperse spherical AgNPs, as it allows control of the nucleation, growth and stabilization of the synthesis process.This work was supported by the Polish Ministry of Science and Higher Education within Research Grant No. NN507 350435 and by the National Science Centre Poland Grant No. 2014/13/B/NZ5/01356

Security theory and practice: Special missions unit GROM: an instrument of the security policy of The Republic of Poland. Thirtieth anniversary of the formation

Z przedmowy: "W tym roku przypada 30. rocznica powołania do życia Jednostki Wojskowej GROM. Decyzja o utworzeniu Jednostki została podjęta przez rząd premiera Tadeusza Mazowieckiego 13 lipca 1990 roku. Generał Petelicki dołożył wszelkich starań, by nowo powstała Jednostka dorównywała umiejętnościami i wyszkoleniem najlepszym jednostkom specjalnym na świecie oraz by jako równorzędny partner mogła z nimi prowadzić zadania na teatrze działań wojennych. Kolejni Dowódcy kontynuowali zamysł Generała, utrzymując najwyższy poziom wyszkolenia oraz ciągle zwiększając możliwości i zdolności bojowe Jednostki dzięki doświadczeniom nabytym podczas misji oraz licznych szkoleń w kraju i za granicą. Budowanie jednostki od początku oparte było na najlepszych praktykach i doświadczeniach zagranicznych oddziałów sił specjalnych, w szczególności tych ze Stanów Zjednoczonych i Wielkiej Brytanii."(...

Microgrid Operation Optimization Using Hybrid System Modeling and Switched Model Predictive Control

Optimization of economic aspects of microgrid operation in both grid-connected and islanded mode leads to contradictive definitions of optimality for both modes. There is no general agreement on how to cope with this duality. To address this issue, as well as modern energy market requirements and a better renewable energy utilization necessity in the case of large facilities, a comprehensive control solution utilizing the appropriate model is needed. In response, the authors propose a hybrid microgrid model covering fundamental features and designed to work in conjunction with two switched receding horizon control laws. A relevant controller is chosen according to the current microgrid operation mode and its cost function tailored to specific demands of the islanded or grid-connected operation. Performed research led to a new switched hybrid model predictive control approach focused on microgrid economic optimization. This approach utilizes an appropriate hybrid microgrid model also contributed by the authors. The introduced solution turned out to be effective in overall energy cost reduction in the case of large commercial facilities, regardless of grid-connection and renewable generation scenarios. Furthermore, it also provides satisfactory renewable energy and storage capabilities utilization in changing grid connection conditions

Luenberger Observer Gain Optimization in Model Predictive Control System for Car Active Suspension

Układy sterowania wykorzystujące regulatory predykcyjne bardzo często wymagają wprowadzenia do ich struktury mechanizmów umożliwiających estymację niedostępnego pomiarowo stanu obiektu. Zależnie od przypadku nieosiągalne mogą być informacje o różnej liczbie zmiennych stanu. Szeroko stosowanymi układami pozwalającymi na uzyskanie niezbędnych informacji o stanie obiektu są obserwator Luenbergera oraz różnego typu filtry Kalmana. Autorzy proponują metodę syntezy obserwatora Luenbergera opartą na optymalizacji wzmocnienia owego obserwatora, przy czym wyznacznik jakości uzyskanego wzmocnienia wykorzystywanego przez optymalizator stanowi ogólna jakość regulacji układu sterowania z regulatorem predykcyjnym. Opracowana metoda pozwala na uzyskanie, z punktu widzenia przyjętego kryterium, obserwatora o właściwościach lepszych niż analogiczny układ, którego syntezę przeprowadzono przy wykorzystaniu równania Sylvestera oraz klasycznego filtru Kalmana, mimo występowania zakłóceń. Metoda zaprezentowana zostanie na przykładzie układu predykcyjnego sterowania systemem aktywnego zawieszenia.MPC Driven control systems very often are requiring the introduction of a mechanism predicting the state of the object unavailable for measurements. Depending on the case, a different number of state variables will be unobtainable. Widely used systems to obtain essential data of the condition of an object are Luenberger state observer and different types of Kalman filters. The authors propose a new method of Luenberger observer synthesis based on Luenberger gain optimization using performance index corresponding to generalized system performance. The developed method allows us to obtain better-performing observer from the point of view of the adopted criterion, compared to similar estimators derived from the Sylvester equation and classic Kalman filters, even despite the occurrence of disturbances. The developed method will be presented on an example of an active suspension system with MPC

Microgrid Operation Optimization Using Hybrid System Modeling and Switched Model Predictive Control

Optimization of economic aspects of microgrid operation in both grid-connected and islanded mode leads to contradictive definitions of optimality for both modes. There is no general agreement on how to cope with this duality. To address this issue, as well as modern energy market requirements and a better renewable energy utilization necessity in the case of large facilities, a comprehensive control solution utilizing the appropriate model is needed. In response, the authors propose a hybrid microgrid model covering fundamental features and designed to work in conjunction with two switched receding horizon control laws. A relevant controller is chosen according to the current microgrid operation mode and its cost function tailored to specific demands of the islanded or grid-connected operation. Performed research led to a new switched hybrid model predictive control approach focused on microgrid economic optimization. This approach utilizes an appropriate hybrid microgrid model also contributed by the authors. The introduced solution turned out to be effective in overall energy cost reduction in the case of large commercial facilities, regardless of grid-connection and renewable generation scenarios. Furthermore, it also provides satisfactory renewable energy and storage capabilities utilization in changing grid connection conditions

Effect of Brood Age on Nestling Diet and Prey Composition in a Hedgerow Specialist Bird, the Barred Warbler Sylvia nisoria.

The composition and quality of food provided to nestling birds influence their growth and development and offers key insight into the ecological requirements of birds. One bird species whose feeding ecology is poorly understood is the Barred Warbler (Sylvia nisoria), which utilizes semi-natural shrubby vegetation in agroecosystems. Because Barred Warbler nestlings vary greatly in body mass we hypothesised that diet and prey properties (size, diversity, taxonomic composition, and chitin content and resulting body hardness and digestibility) would differ as the nestlings aged. We quantified the diet based on faecal analysis, sampling faecal sacs from the nestlings pooled into three age classes: 2-3 days old, 4-6 d old, and 7-9 d old. Nestlings were provided a wide diversity of food and a strong relationship existed between food characteristics and nestling age. The youngest nestlings (2-3 d old) had the lowest values of each dietary characteristic (diversity, number and total biomass of prey, and individual prey weight), that were significantly lower than the oldest nestlings (7-9 d old). Nestlings aged 4-6 d exhibited intermediate dietary characteristics. Differences in dietary composition of the six major food types showed marked differences between the individual broods and age categories. Percentages of the number and biomass of soft-bodied prey were highest in the diet of 2-3 d and 4-6 d old nestlings, and decreased with increasing age, whereas the opposite trend was observed in the percentage of intermediately and heavily chitinised prey. Parent Barred Warblers probably preferentially select soft-bodied prey for the youngest nestlings, and satisfy the greater energy demands of the older ones by providing them with a greater variety of prey containing more chitin, as well as plant food. The provisioning of less-readily digestible prey to older nestlings suggests that as the quality of food decreases the quantity increases, implying that the youngest nestlings may be physiologically limited as regards their ability to digest more heavily chitinised prey

Functional Invertebrate Prey Groups Reflect Dietary Responses to Phenology and Farming Activity and Pest Control Services in Three Sympatric Species of Aerially Foraging Insectivorous Birds

<div><p>Farming activity severely impacts the invertebrate food resources of farmland birds, with direct mortality to populations of above-ground arthropods thorough mechanical damage during crop harvests. In this study we assessed the effects of phenological periods, including the timing of harvest, on the composition and biomass of prey consumed by three species of aerial insectivorous birds. Common Swifts <i>Apus apus</i>, Barn Swallows <i>Hirundo rustica</i> and House Martins <i>Delichon urbica</i> breed sympatrically and most of their diet is obtained from agricultural sources of invertebrate prey, especially from oil-seed rape crops. We categorized invertebrate prey into six functional groups, including oil-seed rape pests; pests of other arable crops; other crop-provisioned taxa; coprophilous taxa; and taxa living in non-crop and mixed crop/non-crop habitats. Seasonality impacted functional groups differently, but the general direction of change (increase/decrease) of all groups was consistent as indexed by prey composition of the three aerial insectivores studied here. After the oil-seed rape crop harvest (mid July), all three species exhibited a dietary shift from oil-seed rape insect pests to other aerial invertebrate prey groups. However, Common Switfts also consumed a relative large quantity of oil-seed rape insect pests in the late summer (August), suggesting that they could reduce pest insect emigration beyond the host plant/crop. Since these aerially foraging insectivorous birds operate in specific conditions and feed on specific pest resources unavailable to foliage/ground foraging avian predators, our results suggest that in some crops like oil-seed rape cultivations, the potential integration of the insectivory of aerial foraging birds into pest management schemes might provide economic benefits. We advise further research into the origin of airborne insects and the role of aerial insectivores as agents of the biological control of crop insect pests, especially the determination of depredation rates and the cascading effects of insectivory on crop damage and yield.</p></div

Percentage composition (average±SE) of the number of six functional aerial invertebrate prey groups identified in individual faecal sacs of nestlings of Common Swifts <i>Apus apus</i> (□), Barn Swallows <i>Hirundo rustica</i> (▴) and House Martins <i>Delichon urbica</i> (•) in various periods of the breeding season 2012; note different scales on y-axes; the harvest of oil-seed rape crops (15–20 July) is indicated by the vertical dotted grey line; for Common Swifts, Barn Swallows and House Martins the number of faecal sacs analysed in consecutive periods was: 25–30 May (0/0/4), 1–15 June (0/27/62), 16–30 June (10/76/33), 1–14 July (17/7/35), 15–20 July (66/35/27), 21–31 July (9/14/13), 1–15 August (10/65/45), 16–31 August (0/22/18), 1–7 September (0/0/35).

<p>Percentage composition (average±SE) of the number of six functional aerial invertebrate prey groups identified in individual faecal sacs of nestlings of Common Swifts <i>Apus apus</i> (□), Barn Swallows <i>Hirundo rustica</i> (▴) and House Martins <i>Delichon urbica</i> (•) in various periods of the breeding season 2012; note different scales on y-axes; the harvest of oil-seed rape crops (15–20 July) is indicated by the vertical dotted grey line; for Common Swifts, Barn Swallows and House Martins the number of faecal sacs analysed in consecutive periods was: 25–30 May (0/0/4), 1–15 June (0/27/62), 16–30 June (10/76/33), 1–14 July (17/7/35), 15–20 July (66/35/27), 21–31 July (9/14/13), 1–15 August (10/65/45), 16–31 August (0/22/18), 1–7 September (0/0/35).</p