Ncs2* mediates in vivo virulence of pathogenic yeast through sulphur modification of cytoplasmic transfer RNA.

Fungal pathogens threaten ecosystems and human health. Understanding the molecular basis of their virulence is key to develop new treatment strategies. Here, we characterize NCS2*, a point mutation identified in a clinical baker's yeast isolate. Ncs2 is essential for 2-thiolation of tRNA and the NCS2* mutation leads to increased thiolation at body temperature. NCS2* yeast exhibits enhanced fitness when grown at elevated temperatures or when exposed to oxidative stress, inhibition of nutrient signalling, and cell-wall stress. Importantly, Ncs2* alters the interaction and stability of the thiolase complex likely mediated by nucleotide binding. The absence of 2-thiolation abrogates the in vivo virulence of pathogenic baker's yeast in infected mice. Finally, hypomodification triggers changes in colony morphology and hyphae formation in the common commensal pathogen Candida albicans resulting in decreased virulence in a human cell culture model. These findings demonstrate that 2-thiolation of tRNA acts as a key mediator of fungal virulence and reveal new mechanistic insights into the function of the highly conserved tRNA-thiolase complex

E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation.

Post-translational modifications by ubiquitin-like proteins (UBLs) are essential for nearly all cellular processes. Ubiquitin-related modifier 1 (Urm1) is a unique UBL, which plays a key role in tRNA anticodon thiolation as a sulfur carrier protein (SCP) and is linked to the noncanonical E1 enzyme Uba4 (ubiquitin-like protein activator 4). While Urm1 has also been observed to conjugate to target proteins like other UBLs, the molecular mechanism of its attachment remains unknown. Here, we reconstitute the covalent attachment of thiocarboxylated Urm1 to various cellular target proteins in vitro, revealing that, unlike other known UBLs, this process is E2/E3-independent and requires oxidative stress. Furthermore, we present the crystal structures of the peroxiredoxin Ahp1 before and after the covalent attachment of Urm1. Surprisingly, we show that urmylation is accompanied by the transfer of sulfur to cysteine residues in the target proteins, also known as cysteine persulfidation. Our results illustrate the role of the Uba4-Urm1 system as a key evolutionary link between prokaryotic SCPs and the UBL modifications observed in modern eukaryotes

Barcode recognition system "Barmancode" - design and implementation

Celem niniejszej pracy będzie przedstawienie etapu projektowania oraz implementacji systemu Barmancode, , który udostępnia dane o produktach wraz z jej ceną i lokalizacją w twojej okolicy. Niniejsza omawia budowę trzech wersji systemu Barmancode – wersję na platformę Android, wersję desktopową oraz aplikacje webową dostępną pod adresem Barmancode.com.Na początku omówiony zostanie temat projektu . Praca skupi się na przybliżeniu pewnych rozwiązań zastosowanych w systemie – m.in. API BARMANCODE. W pracy będą również zawarte informacje dotyczące modelowaniu w języku UML oraz inne informacje potrzebne by móc jak najlepiej zrozumieć budowę projektu oraz zastosowane w nim rozwiązania.The aim of this study is to present the design phase and implementation Barmancode system, which provides data on products along with its price and location in your area.This work will focus mainly on three versions of Barmancode - version of the Android platform, version of desktop and web-based applications available at Barmancode.com.At the beginning of this work the project will be discussed. Work will focus on approximately some solutions used in the system - including API BARMANCODE.The work will also include information on modeling in UML and other information needed to be able to best understand the structure of the project and used in the solution

Telemedicine monitoring of elderly patients

Rozwijająca się technologia coraz bardziej ułatwia nam życie codzienne. Przykładem tego są inteligentne zegarki które są coraz bardziej zaawansowane technologicznie. Taki zegarek daje nam dostęp do wielu danych o użytkowniku które są odczytywane przez sensory. Niniejsza praca przedstawia możliwości pomiarowe takiego zegarka w celu wykrywania określonych zdarzeń za pomocą algorytmów. Głównym celem jest wykrywanie zdarzeń takich jak: anomalia bicia serca, upadek czy atak drgawek. Przedstawiony został projekt aplikacji na inteligentny zegarek z systemem Wear oraz aplikacji klienckiej na telefon z systemem Android. Aplikacja jest otwarta na przyszły rozwój w celu dodania nowych algorytmów a już istniejące mają możliwość konfiguracji z poziomu aplikacji klienckiej. Zaznaczone zostały kluczowe elementy aplikacji i rozwiązania jakie w nich zastosowano. Rozwiązanie zostało przetestowane przez pewną grupę osób. Każda z nich miała za zadanie wykonać kilka testów w celu zebrania danych testowych. Posłużyły one do odtworzenia sytuacji w celu usprawnienia oraz oszacowania dokładności algorytmów. Wyniki testów pokazały, że aplikacja może być z powodzeniem używana przez osoby w podeszłym wieku.Developing technology makes everyday life easier for us. An example of this are smartwatches that are increasingly technologically advanced. A smartwatch gives us access to many data about the user that are read by sensors. This thesis presents the measurement capabilities of a smartwatch in order to detect specific events using algorithms. The main purpose is to detect events such as heartbeat anomalies, falls or seizures. The project of an application for a smartwatch with the Wear OS and a client application for an Android phone was presented. The application is open to future development in order to add new algorithms and the existing ones can be configured from the client application. The key elements of the application and the solutions used in them are marked. The solution was tested by a certain group of people. Each of them was tasked with performing several tests to collect test data. They were used to recreate the situation in order to improve and estimate the accuracy of the algorithms. The test results showed that the application can be successfully used by the elderly

Effect of Post-Weld Heat Treatment on Microstructure and Hardness of Laser Beam Welded 17-4 PH Stainless Steel

This article presents the results of research on the development of the technology of laser beam butt welding of 17-4 PH stainless steel sheets and the technology of post-weld heat treatment (PWHT). The developed technology allows for favorable conditions to be obtained and for the appropriate microstructure and hardness to exist in the weld area. Moreover, it enables the fulfillment of a number of specific requirements beyond the possibilities of manual welding and other methods. The tests performed include the analysis of the microstructure with the use of light microscopy (LM) for the materials after welding and PWHT. The applied PWHT showed changes in the microstructure and mechanical properties. In all weld areas the martensitic microstructure was observed. The homogeneity of the microstructure in the area of the welded joint after PWTH was revealed. In the as-welded condition and after the PWHT with aging at 481 °C, the hardness was 440 HV5, but after aging at 621 °C, it decreased to 330–340 HV5

Effect of Post-Weld Heat Treatment on Microstructure and Hardness of Laser Beam Welded 17-4 PH Stainless Steel

This article presents the results of research on the development of the technology of laser beam butt welding of 17-4 PH stainless steel sheets and the technology of post-weld heat treatment (PWHT). The developed technology allows for favorable conditions to be obtained and for the appropriate microstructure and hardness to exist in the weld area. Moreover, it enables the fulfillment of a number of specific requirements beyond the possibilities of manual welding and other methods. The tests performed include the analysis of the microstructure with the use of light microscopy (LM) for the materials after welding and PWHT. The applied PWHT showed changes in the microstructure and mechanical properties. In all weld areas the martensitic microstructure was observed. The homogeneity of the microstructure in the area of the welded joint after PWTH was revealed. In the as-welded condition and after the PWHT with aging at 481 °C, the hardness was 440 HV5, but after aging at 621 °C, it decreased to 330–340 HV5

Molecular basis for the bifunctional Uba4–Urm1 sulfur‐relay system in tRNA thiolation and ubiquitin‐like conjugation

The chemical modification of tRNA bases by sulfur is crucial to tune translation and to optimize protein synthesis. In eukaryotes, the ubiquitin-related modifier 1 (Urm1) pathway is responsible for the synthesis of 2-thiolated wobble uridine (U34 ). During the key step of the modification cascade, the E1-like activating enzyme ubiquitin-like protein activator 4 (Uba4) first adenylates and thiocarboxylates the C-terminus of its substrate Urm1. Subsequently, activated thiocarboxylated Urm1 (Urm1-COSH) can serve as a sulfur donor for specific tRNA thiolases or participate in ubiquitin-like conjugation reactions. Structural and mechanistic details of Uba4 and Urm1 have remained elusive but are key to understand the evolutionary branch point between ubiquitin-like proteins (UBL) and sulfur-relay systems. Here, we report the crystal structures of full-length Uba4 and its heterodimeric complex with its substrate Urm1. We show how the two domains of Uba4 orchestrate recognition, binding, and thiocarboxylation of the C-terminus of Urm1. Finally, we uncover how the catalytic domains of Uba4 communicate efficiently during the reaction cycle and identify a mechanism that enables Uba4 to protect itself against self-conjugation with its own product, namely activated Urm1-COSH

Effect of environmental parameters on the concentration of nickel (Ni) in bones of the hip joint from patients with osteoarthritis

Introduction. Bone trace elements levels including nickel (Ni) depend on biological and environmental factors: age, gender, remodeling state, exposure to occupational and environmental pollution, smoking, diet, and surgical implants. Objective. The aim of this study was to determine Ni concentrations in bones of femur heads obtained from patients with osteoarthritis. Materials and method. A total of 111 samples of hip joint bones (cartilage, cancellous bone and compact bone) collected from patients from north-western Poland were examined. Ni concentration was determined by ICP-AES (atomic absorption spectrophotometry). Results. It was found that differences in Ni concentrations were statistically significant between cartilage and compact bone. Cartilage Ni concentrations were higher in patients with fractured femur neck than patients with osteoarthritis. Furthermore, higher Ni levels were also found in samples obtained from smokers compared to nonsmokers. In cancellous bone, higher Ni concentrations were found in samples from patients who had received implants than those without them. Moreover, higher Ni concentrations in cancellous bone were found in patients occupationally exposed to heavy metals than in those not exposed. Conclusions. The bone tissue reflects long-term exposure to Ni and may be used as a bioindicator to study the process of Ni accumulation in the human body

Catalytic reductions of nitroaromatic compounds over heterogeneous catalysts with rhenium sub-nanostructures

Abstract Nitroaromatic compounds (NACs) are key contaminants of anthropogenic origin and pose a severe threat to human and animal lives. Although the catalytic activities of Re nanostructures (NSs) are significantly higher than those of other heterogeneous catalysts containing NSs, few studies have been reported on the application of Re-based nanocatalysts for NAC hydrogenation. Accordingly, herein, catalytic reductions of nitrobenzene (NB), 4-nitrophenol (4-NP), 2-nitroaniline (2-NA), 4-nitroaniline (4-NA), and 2,4,6-trinitrophenol (2,4,6-TNP) over new Re-based heterogeneous catalysts were proposed. The catalytic materials were designed to enable effective syntheses and stabilisation of particularly small Re structures over them. Accordingly, catalytic hydrogenations of NACs under mild conditions were significantly enhanced by Re sub-nanostructures (Re-sub-NSs). The highest pseudo-first-order rate constants for NB, 4-NP, 2-NA, 4-NA, and 2,4,6-TNP reductions over the catalyst acquired by stabilising Re using bis(3-aminopropyl)amine (BAPA), which led to Re-sub-NSs with Re concentrations of 16.7 wt%, were 0.210, 0.130, 0.100, 0.180, and 0.090 min−1, respectively

Usefulness of C2HEST Score in Predicting Clinical Outcomes of COVID-19 in Heart Failure and Non-Heart-Failure Cohorts

Background: Patients with heart failure represent a vulnerable population for COVID-19 and are prone to having worse prognoses and higher fatality rates. Still, the clinical course of the infection is dynamic, and complication occurrence in particular in patients with heart failure is fairly unpredictable. Considering that individual components of the C2HEST (C2: Coronary Artery Diseases (CAD)/Chronic obstructive pulmonary disease (COPD); H: Hypertension; E: Elderly (Age ≥ 75); S: Systolic HF; T: Thyroid disease) are parallel to COVID-19 mortality risk factors, we evaluate the predictive value of C2HEST score in patients with heart failure (HF) Material and Methods: The retrospective medical data analysis of 2184 COVID-19 patients hospitalized in the University Hospital in Wroclaw between February 2020 and June 2021 was the basis of the study. The measured outcomes included: in-hospital mortality, 3-month and 6-month all-cause-mortality, non-fatal end of hospitalization, and adverse in-hospital clinical events. Results: The heart failure cohort consists of 255 patients, while 1929 patients were assigned to the non-HF cohort. The in-hospital, 3-month, and 6-month mortality rates were highest in the HF cohort high-risk C2HEST stratum, reaching 38.61%, 53.96%, and 65.36%, respectively. In the non-HF cohort, in-hospital, 3-month, and 6-month mortalities were also highest in the high-risk C2HEST stratum and came to 26.39%, 52.78%, and 65.0%, respectively. An additional point in the C2HEST score increased the total death intensity in 10% of HF subjects (HR 1.100, 95% CI 0.968–1.250 p = 0.143) while in the non-HF cohort, the same value increased by 62.3% (HR 1.623, 95% CI 1.518–1.734 p < 0.0001). Conclusions: The C2HEST score risk in the HF cohort failed to show discriminatory performance in terms of mortality and other clinical adverse outcomes during hospitalization. C2HEST score in the non-HF cohort showed significantly better performance in terms of predicting in-hospital and 6-month mortality and other non-fatal clinical outcomes such as cardiovascular events (myocardial injury, acute heart failure, myocardial infarction, cardiogenic shock), pneumonia, sepsis, and acute renal injury