EPIYA (or -like) motifs in mammalian proteins

AbstractRecently, two mammalian proteins with functional Glu-Pro-Ile-Tyr-Ala (EPIYA) or a similar sequence (EPIYA-like motif) have been identified. Pragmin contains a single EPIYA motif and p140Cap contains two EPIYA-like motifs (EPLYA/EGLYA). Searching the human proteome using the NCBI BLAST software revealed that EPIYA-like motifs such as EPLYA, ESIYE, EDLYA, ESIYA, EHIYD, EPIYD, ENIYE, EPVYA, EVVYA, and TPLYA (which are present in bacterial effectors and have roles in virulence) are present in mammalian proteins. Moreover, several of bacterial EPIYA-like motifs were duplicated in mammalian proteins. Since, only five mammalian proteins contain EPIYA motif, and there are no mammalian proteins with more than one copy of the EPIYA motif. We also showed that the most of EPIYA (or -like) motifs in mammalian proteins are predicted to be naturally ordered. Moreover, few mammalian proteins containing EPIYA (or -like) motif were tyrosine phosphorylated. On the other hand, most of the mammalian proteins contain “unfunctional EPIYA (or -like) motifs”. Notably, regulation of Src family kinases’ (SFKs) activity (including up and down regulation) originally is mediated by their own EPIYA like motifs (EPIYI and EPQYQ) and thereby, it seems that EPIYA (or -like) motifs are “potential regulators of SFKs”. Therefore, it can explain why EPIYA (or -like) motifs are restricted sites with low copy number in most mammalian proteins whereas in bacterial effector proteins, they can be universal sites with repetitive copies. In this study, we identified new mammalian proteins which contain functional EPIYA (or -like) motifs and thereby, their possible roles in cell signal transduction pathways. In this respect, functional experiments will be necessary to confirm our findings

Historia kryształów rezorcynolu i nowe sposoby stabilizowania wysokociśnieniowych polimorfów w warunkach normalnych

Wydział ChemiiMy thesis tells The story of resorcinol crystals and a new perspective for stabilizing high-pressure polymorphs at ambient conditions. Resorcinol is an important natural product and chemical compound of many applications, including technological ones. Resorcinol is also important from the point of view of the history of science, as it was the first organic compound for which the structures of two polymorphs were determined by X-ray diffraction in the 1930s. Actually, those historic determinations were puzzling, and they continued to be puzzling in the most recent times, because both polymorphs have the same space-group symmetry type and the high-temperature polymorph β is denser than the low-temperature one (α); in 2016 a still denser polymorph ε was discovered, which was even more puzzling. I have shown that polymorph β is not stable under pressure, as it was suggested, and that polymorph ε is the high-pressure form of resorcinol between 0.2 and 0.7 GPa, above which still another new polymorph ζ is stable. This was a surprising outcome because polymorph ε was discovered under ambient pressure (0.1 MPa), but only in the mixture with tartaric acid and with polymorph β. I have obtained polymorph ε in its pure form (without additions), as a single crystal, and I have shown that it is unstable below 0.2 GPa. I have also shown that resorcinol is prone to form solvates under pressure: I have obtained two new hydrates (mono- and duotritohydrate) and the methanol solvate. These solvates are quite intriguing by themselves, as the monohydrate and mono-methanol solvates are isostructural, but the monohydrate is metastable with respect to duotritohydrate, while the duotritomethanol solvate was not found. Also, the duotritohydrate forms a passivation layer on the surface of monohydrate crystals, protecting the metastable phase from dissolution. I established that it is characteristic to all resorcinol phases that they transform between phases with a wide hysteresis, which hampers the investigations of resorcinol forms. Therefore, I had to use the methods of high-pressure in situ isothermal and isochoric recrystallizations in the diamond anvil cell for outlining the pressure/temperature phase diagram and also the preference diagram for the solvates. I consider the discovery of the new polymorph ζ of resorcinol and of the solvates and their stability relations to be a significant achievement. Particularly, polymorph ζ is the first layered structure of pure resorcinol and the first centrosymmetric structure. As for the general achievements, the phase diagram of pure resorcinol indicated that polymorph ε cannot exist under ambient pressure and therefore it was somehow stabilized – I found the method of stabilizing high-pressure phases and tested it not only for resorcinol, but also for other compounds. Thus, this new method to recover and stabilize high-pressure polymorphs is quite general method for other organic compounds. In fact, my research shows that high-pressure polymorphs can be used for practical applications, which can solve one of the big challenges of high-pressure research, i.e. overcoming the instability of the obtained high-pressure polymorphs at ambient conditions. Some of the puzzles connected to the polymorphism of resorcinol still remain unsolved, but certainly many new information about the polymorphs and crystalline forms of resorcinol have been provided in my thesis. Besides the thesis, these results have been summarized in three articles on resorcinol published in Crystal Growth & Design and in Journal of Physical Chemistry C. In the first article (R1), I show that the polymorphs α and β can be compressed up to 5.6 GPa and that their α-to-β phase transition does not occur at 0.5 GPa. However, the hydrogen bonds network in polymorphs α show some destabilizing effects close to 0.5 GPa, which is due to the molecular reorientations in the compressed crystal environment. This structural feature of hydrogen bonds OH∙∙∙O can be the reason for observations by the NMR and IR techniques of the α-to-β phase transition reported in the literature. Solvates of resorcinol with water and methanol have been discussed in article R2. The monohydrate and duotritohydrate revealed a formation of the passivation layer protecting the metastable form from dissolution. Surprisingly, the duotritohydrate, the more stable and higher-pressure form is disordered, while the monohydrate contains geometrically unfavourable hydrogen bond (by over 0.3 Å longer than expected for OH∙∙∙O bonds) in its structure. In article R3, two new high-pressure polymorphs ε and ζ of resorcinol have been revealed. Moreover, in this paper, we stabilized the high-pressure polymorph ε at ambient conditions by doping the resorcinol sample with tartaric acid. We have explained the mechanism leading to this stabilization by the effect of internal pressure. The range of this internal pressure induced by doping can be calculated according to the formula based on our model. These results of high-pressure polymorph stabilization for resorcinol have been consistent also for other well-known compounds (imidazole and benzimidazole derivatives), for which high-pressure polymorphs were obtained previously.Moja praca dyplomowa opowiada Historię kryształów rezorcynolu i nowych sposobów stabilizowania wysokociśnieniowych polimorfów w warunkach normalnych. Rezorcynol jest ważnym produktem naturalnym i związkiem chemicznym o wielu zastosowaniach, w tym technologicznych. Rezorcynol jest również ważny z punktu widzenia historii nauki, ponieważ był pierwszym związkiem organicznym dla którego w latach 30-tych XX wieku określono struktury dwóch odmian polimorficznych metodą dyfrakcji rentgenowskiej. Jednakże, uzyskane wtedy wyniki nawet do niedawna stanowiły zagadkę, ponieważ obie formy mają symetrię tej samej grupy przestrzennej, a wysokotemperaturowa odmiana β ma wyższą gęstość niż niskotemperaturowa odmiana polimorficzna (α); w 2016 roku odkryto formę ε o jeszcze wyższej gęstości, co było jeszcze bardziej zagadkowe. Wykazałam, że wbrew wcześniejszym przypuszczeniom to nie odmiana polimorficzna β jest stabilna pod ciśnieniem, lecz faza ε jest wysokociśnieniową formą rezorcynolu w ciśnieniu w zakresie między 0,2 a 0,7 GPa, a powyżej tego ciśnienia stabilna jest jeszcze inna forma rezorcynolu, nowy polimorf ζ. Był to zaskakujący wynik, ponieważ odmiana polimorficzna ε odkryta została pod ciśnieniem atmosferycznym (0,1 MPa), jednak otrzymana została jedynie, gdy w próbce znajdowała się domieszka kwasu winowego i polimorfu β. W wyniku moich badań uzyskałam formę ε w czystej postaci (bez dodatków) jako monokryształ i wykazałam, że jest ona niestabilna poniżej 0,2 GPa. Wykazałam również, że rezorcynol ma skłonność do tworzenia solwatów pod ciśnieniem: uzyskałam dwa nowe hydraty (mono- i duotritohydrat) oraz solwat z metanolem. Odkryte solwaty są same w sobie dość intrygujące, ponieważ monohydrat i solwat z metanolem (w stosunku 1:1) są izostrukturalne, ale monohydrat jest metastabilny w stosunku do duotritohydratu, podczas gdy solwat duotritometanolu nie został znaleziony. Ponadto, duotritohydrat tworzy warstwę pasywacyjną na powierzchni kryształów monohydratu, dzięki czemu są one chronione przed rozpuszczeniem pomimo ich metastabilności. Stwierdziłam, że dla wszystkich faz rezorcynolu charakterystyczne jest występowanie dużej histerezy dla przejść między fazami, co utrudnia ich badania. Dlatego w celu określenia ciśnieniowo-temperaturowego wykresu fazowego oraz wykresu warunków tworzenia solwatów, konieczne było zastosowanie metod izotermicznej i izochorycznej rekrystalizacji wysokociśnieniowej z zastosowaniem komory z kowadełkami diamentowymi. Uważam, że odkrycie nowej odmiany polimorficznej ζ i solwatów rezorcynolu, oraz wyznaczenie zakresów ich stabilności są znaczącym osiągnięciem. W szczególności odkrycie formy ζ, która jest pierwszą warstwową strukturą czystego rezorcynolu i pierwszą strukturą centrosymetryczną. W kontekście ogólnych osiągnięć, wykazałam na podstawie diagramu fazowego czystego rezorcynolu, że odmiana ε nie może istnieć pod ciśnieniem atmosferycznym w związku z czym musi ona być w jakiś sposób ustabilizowana. Doprowadziło mnie to do znalezienia metody stabilizacji faz wysokociśnieniowych, która przetestowana została nie tylko dla rezorcynolu, ale także dla innych związków. Zatem, ta nowa metoda uzyskiwania i stabilizacji wysokociśnieniowych odmian polimorficznych stosowana być może dla innych związków organicznych. Moje badania pokazują więc, że wysokociśnieniowe odmiany polimorficzne mogą być wykorzystane w praktyce, dzięki rozwiązaniu jednego z wielkich wyzwań badań wysokociśnieniowych, tj. przezwyciężenia niestabilności otrzymanych wysokociśnieniowych odmian polimorficznych w warunkach atmosferycznych. Niektóre zagadki związane z polimorfizmem rezorcynolu wciąż pozostają nierozwiązane, niemniej moja praca z pewnością dostarcza wiele nowych informacji na temat odmian polimorficznych i form krystalicznych tego związku. Wyniki stanowiące podstawę tej dysertacji, zostały podsumowane w trzech artykułach naukowych na temat rezorcynolu opublikowanych w czasopismach Crystal Growth & Design oraz w Journal of Physical Chemistry C. W pierwszym artykule (R1) pokazuję, że odmiany polimorficzne α i β mogą zostać ściśnięte do ciśnienia równego 5,6 GPa bez zajścia przejścia fazowego z formy α do β w ciśnieniu 0,5 GPa. Niemniej sieć wiązań wodorowych w odmianie polimorficznej α wykazuje pewne efekty destabilizujące w ciśnieniu bliskim 0,5 GPa, co spowodowane jest zmianą położenia cząsteczek w ściśniętym krysztale. To z kolei może być powodem zaobserwowania przejścia fazowego z formy α do β, opisanego w literaturze na podstawie wyników badań NMR i IR. Solwaty rezorcynolu z wodą i metanolem zostały omówione w artykule R2. Monohydrat i duotritohydrat ujawniły tworzenie się warstwy pasywacyjnej chroniącej formę metastabilną przed rozpuszczeniem. Co zaskakujące, duotritohydrat, bardziej stabilna forma powstająca w wyższym ciśnieniu jest nieuporządkowana, a w strukturze monohydratu występuje geometrycznie niekorzystne wiązanie wodorowe (o ponad 0,3 Å dłuższe niż by oczekiwano dla wiązań OH∙∙∙O). W artykule R3 przedstawiłam dwie nowe wysokociśnieniowe odmiany polimorficzne ε i ζ rezorcynolu. Ponadto w tej publikacji pokazałam, że wysokociśnieniową odmianę polimorficzną ε można ustabilizować w warunkach atmosferycznych poprzez domieszkowanie próbki rezorcynolu kwasem winowym. Mechanizm prowadzący do tej stabilizacji wyjaśniliśmy efektem ciśnienia wewnętrznego. Zakres tego wewnętrznego ciśnienia wywołanego domieszkowaniem można obliczyć według wzoru opartego na naszym modelu. Wyniki stabilizacji wysokociśnieniowej odmiany polimorficznej rezorcynolu są zgodne z wynikami uzyskanymi dla innych dobrze znanych związków (pochodnych imidazolu i benzimidazolu), których wysokociśnieniowe odmiany polimorficzne zostały otrzymane w przeszłości

Concurrent Hand and Penile Gangrene following Prolonged Warfarin Use; a Case Report

Warfarin induced skin necrosis (WISN) is a rare but important side effect of warfarin. Early diagnosis may lessen the amount of permanent tissue damage and can prevent progression to full thickness skin necrosis. So, physicians should be aware of such a complication. Screening for protein C or S or anti-thrombin deficiencies, or presence of anti-phospholipid antibodies before beginning warfarin therapy, could be helpful to avoid high levels of international normalized ratio (INR). Here, we report a 54-year-old man who presented to the emergency department with acral and penile gangrene following prolonged use of warfarin.

P-TYPE SEMICONDUCTOR SENSITIZED SOLAR CELLS

Master'sMASTER OF ENGINEERIN

One-year outcomes of MTA and modified Portland cement pulpotomy in primary teeth: a randomized clinical trial

Purpose: To compare the efficacy of Mineral Trioxide Aggregate (MTA) and Modified Portland Cement (MPC) as pulpotomy medicaments in primary molars.   Methods: A sample of 54 children 4 to 6 years old of age, who had at least one primary mandibular second molar that needed pulpotomy were randomly placed in MTA (n = 28) or MPC (n = 26) groups. After completing the pulpotomy procedures, the teeth received a stainless-steel crown. Clinical and radiographic successes/failures were blindly evaluated at 6 and 12 months, and Fisher's exact test was used to analyze the differences.  Results: At 6- and 12-month follow-ups, MTA and MPC had 100% clinical success rate. Radiographic success rates of MTA were 92.9% at 6 months and 89.3% at 12 months. While the rate for MPC group was 88.5% at both intervals. There was no statistically significant difference between the two groups.  Conclusion: The results of this investigation showed that treatment success rate with MPC was comparable to MTA pulpotomy. However, additional clinical research that considers long-term follow-ups is required to test the usefulness of MPC in the pulpotomy treatment of primary teeth

Electrocardiographic Findings of COVID-19 Patients and Their Correlation with Outcome; a Prospective Cohort Study

Introduction: Being infected with COVID-19 is associated with direct and indirect effects on the cardiopulmonary system and electrocardiography can aid in management of patients through rapid and early identification of these adversities. Objective: The present study was designed aiming to evaluate electrocardiographic changes and their correlation with the outcome of COVID-19 patients. Methods: This Prospective cohort study was carried out on COVID-19 cases admitted to the emergency department of an educational hospital, during late February and March 2020. Electrocardiographic characteristics of patients and their association with in-hospital mortality were investigated. Results: One hundred and nineteen cases with the mean age of 60.52±13.45 (range: 29-89) years were studied (65.5% male). Dysrhythmia was detected in 22 (18.4%) cases. T-wave inversion (28.6%), pulmonale P-wave (19.3%), left axis deviation (19.3%), and ST-segment depression (16.8%) were among the most frequently detected electrocardiographic abnormalities, respectively. Twelve (10.1%) cases died. There was a significant correlation between in-hospital mortality and history of diabetes mellitus (p=0.007), quick SOFA score > 2 (p<0.0001), premature ventricular contraction (PVC) (p=0.003), left axis deviation (LAD) (p=0.039), pulmonale P-wave (p<0.001), biphasic P-wave (p<0.001), inverted T-wave (p=0.002), ST-depression (p=0.027), and atrioventricular (AV) node block (p=0.002). Multivariate cox regression showed that history of diabetes mellitus, and presence of PVC and pulmonale P-wave were independent prognostic factors of mortality. Conclusions: Based on the findings of the present study, 18.4% of COVID-19 patients had presented with some kind of dysrhythmia and in addition to history of diabetes, presence of PVC and pulmonale P-wave were among the independent prognostic factors of mortality in COVID-19 patients

Morphological plasticity of Nemoura Cinerea (Arthropoda, Nemouridae) as a biological indicator for aquatic systems

Macrobenthos are indicators of the physical and chemical changes in aquatic ecosystems. In this research, the diversity of macrobenthos communities in the Ortkand River, Iran, was investigated during four consecutive seasons using the Shannon-Weiner, EPT richness indices, and the Hilsenhoff index for water quality at four sampling stations. In addition, sampling of Nemoura cinerea (Arthropoda, Nemouridae) was done to compare morphological differences between specimens from two upstream and downstream sites using a geometric morphometric approach. The physicochemical parameters of water were also recorded. The entry of fish farm wastewater significantly affects biotic and abiotic environmental factors according to the Shannon-Weiner and Hilsenhoff indices. The results showed a significant positive correlation between DO and Shannon-Wiener index, TDS and the Hilsenhoff index, and DO and EPT richness index. A significant negative correlation was observed between BOD and the Shannon-Wiener index, DO and Hilsenhoff index, and between BOD and EPT richness index. Geometric morphometrics analyses revealed that the two groups differed mainly in pronotum and metanotum morphology. According to the results, monitoring of macrobenthos can help assess rivers’ water quality, and N. cinerea can be a proper bioindicator