Pivotal Role of Inosine Triphosphate Pyrophosphatase in Maintaining Genome Stability and the Prevention of Apoptosis in Human Cells

Pure nucleotide precursor pools are a prerequisite for high-fidelity DNA replication and the suppression of mutagenesis and carcinogenesis. ITPases are nucleoside triphosphate pyrophosphatases that clean the precursor pools of the non-canonical triphosphates of inosine and xanthine. The precise role of the human ITPase, encoded by the ITPA gene, is not clearly defined. ITPA is clinically important because a widespread polymorphism, 94C>A, leads to null ITPase activity in erythrocytes and is associated with an adverse reaction to thiopurine drugs. We studied the cellular function of ITPA in HeLa cells using the purine analog 6-N hydroxylaminopurine (HAP), whose triphosphate is also a substrate for ITPA. In this study, we demonstrate that ITPA knockdown sensitizes HeLa cells to HAP-induced DNA breaks and apoptosis. The HAP-induced DNA damage and cytotoxicity observed in ITPA knockdown cells are rescued by an overexpression of the yeast ITPase encoded by the HAM1 gene. We further show that ITPA knockdown results in elevated mutagenesis in response to HAP treatment. Our studies reveal the significance of ITPA in preventing base analog-induced apoptosis, DNA damage and mutagenesis in human cells. This implies that individuals with defective ITPase are predisposed to genome damage by impurities in nucleotide pools, which is drastically augmented by therapy with purine analogs. They are also at an elevated risk for degenerative diseases and cancer

Evening Telegram, 1919-10-10

The Evening Telegram began publication in St. John's on 3 April 1879 and remains in print today under the title The Telegram. It was published daily except Sunday through to 1958, the frequency changing thereafter. -- The total collection has been split into several parts; this portion contains the years 1919-1926

The infective endocarditis of synthetic patch after left ventricle reconstruction (Dor procedure)

Infective endocarditis (IE) has become an increasingly significant problem in cardiology and cardiac surgery over the past 30 years. Despite the noticeable progress made in the diagnosis and treatment of IE, the prognosis for this condition is still poor and the mortality rate reaches 15-30% [1, 2]. The risk of developing IE is especially high in patients with «intracardiac» artificial materials (artificial valves, prostheses of any type, implantable antiarrhythmic devices). This article presents a rare clinical case of   IE of synthetic patch after left ventricle reconstruction (Dor procedure)

Antibacterial Performance of TiCaPCON Films Incorporated with Ag, Pt, and Zn Bactericidal Ions Versus Surface Microgalvanic Interactions

It is very important to prevent bacterial colonization at the early postoperative stages. There are four major strategies and their corresponding types of antibacterial surfaces specifically designed to fight infection bactericide release, anti-adhesion, pH-sensitive, and contact-killing. Herein, we aimed at determining the antibacterial efficiency of different types of bactericidal ions and revealing the possible contribution of surface microgalvanic effects arising from a potential difference on heterogeneous surfaces. We considered five types of TiCaPCON films, with Ag, Zn, Pt, Ag + Zn, and Pt + Zn nanoparticles (NPs) on their surface. The Ag-modified film demonstrated a pronounced antibacterial effect at a very low Ag ion concentration of 0.11 ppb in physiological solution that was achieved already after 3 h of immersion in Escherichia coli (E. coli) bacterial culture. The Zn-containing sample also showed a noticeable antibacterial effect against E. coli and Staphylococcus aureus (S. aureus) strains, wherein the concentration of Zn ions was 2 orders of magnitude higher (15 ppb) compared with the Ag ions. The presence of Ag NPs accelerated the leaching of Zn ion out of the TiCaPCON-Ag-Zn film, but no synergistic effect of the simultaneous presence of the two bactericidal components was observed. After the incubation of the samples with Ag, Zn, and Ag + Zn NPs in E. coli and S. aureus suspensions for 24 and 8 h, respectively, all bacterial cells were completely inactivated. The Pt-containing film showed a very low Pt ion release, and therefore the contribution of this type of ions to the total bactericidal effect could be neglected. The results of the electrochemical studies and Kelvin probe force microscopy indicated that microgalvanic couples were formed between the Pt NPs and the TiCaPCON film, but no noticeable antibacterial effect against either E. coli or S. aureus strains was observed. All ion-modified samples provided good osteoblastic cell attachment, spreading, and proliferation and therefore were concluded to be nontoxic for cells. In addition, the TiCaPCON films with Ag, Pt, and Zn NPs on their surface demonstrated good osteoconductive characteristics

Antibacterial Performance of TiCaPCON Films Incorporated with Ag, Pt, and Zn Bactericidal Ions Versus Surface Microgalvanic Interactions

International audienceIt is very important to prevent bacterial colonization at the early postoperative stages. There are four major strategies and their corresponding types of antibacterial surfaces specifically designed to fight infection bactericide release, anti-adhesion, pH-sensitive, and contact-killing. Herein, we aimed at determining the antibacterial efficiency of different types of bactericidal ions and revealing the possible contribution of surface microgalvanic effects arising from a potential difference on heterogeneous surfaces. We considered five types of TiCaPCON films, with Ag, Zn, Pt, Ag + Zn, and Pt + Zn nanoparticles (NPs) on their surface. The Ag-modified film demonstrated a pronounced antibacterial effect at a very low Ag ion concentration of 0.11 ppb in physiological solution that was achieved already after 3 h of immersion in Escherichia coli (E. coli) bacterial culture. The Zn-containing sample also showed a noticeable antibacterial effect against E. coli and Staphylococcus aureus (S. aureus) strains, wherein the concentration of Zn ions was 2 orders of magnitude higher (15 ppb) compared with the Ag ions. The presence of Ag NPs accelerated the leaching of Zn ion out of the TiCaPCON-Ag-Zn film, but no synergistic effect of the simultaneous presence of the two bactericidal components was observed. After the incubation of the samples with Ag, Zn, and Ag + Zn NPs in E. coli and S. aureus suspensions for 24 and 8 h, respectively, all bacterial cells were completely inactivated. The Pt-containing film showed a very low Pt ion release, and therefore the contribution of this type of ions to the total bactericidal effect could be neglected. The results of the electrochemical studies and Kelvin probe force microscopy indicated that microgalvanic couples were formed between the Pt NPs and the TiCaPCON film, but no noticeable antibacterial effect against either E. coli or S. aureus strains was observed. All ion-modified samples provided good osteoblastic cell attachment, spreading, and proliferation and therefore were concluded to be nontoxic for cells. In addition, the TiCaPCON films with Ag, Pt, and Zn NPs on their surface demonstrated good osteoconductive characteristics

Особенности наблюдения неоднородностей намагниченности на поверхности тонких магнитных пленок в Ta/CoFeB/MgO/CoFeB/Ta многослойных структурах

This work presents the results of the study of non-uniformly magnetized regions on the surface of thin magnetic films in multilayer magnetic tunnel junction (MTJ) structure Ta/CoFeB/MgO/CoFeB/Ta ob- served by highly sensitive magnetic force microscopy (MFM) probes. The micromagnetic simulation of the magnetization dynamics in CoFeB magnetic layer after the application of the external magnetic field of 0.5 T is conducted using mumax3 open-source software. The areas of the existence of magnetic vortices and domain walls in CoFeB magnetic film are found where the domain wall thickness was measured by MFM in the nanometer scaleПредставлены результаты исследования неоднородностей намагниченности на поверхности тонких магнитных пленок в структуре многослойного магнитного туннельного перехода (МТП) Ta/CoFeB/MgO/CoFeB/Ta с помощью высокочувствительных зондов МСМ. Проведено микромаг- нитное моделирование магнитной динамики в CoFeB магнитном слое при наведении внешнего магнитного поля величиной 0.5 Тл с использованием программного пакета mumax3. Найдены обла- сти существования магнитных вихрей и доменных стенок в CoFeB магнитной пленки, а также измерены толщины доменных стенок в нанометровом масштаб

Особенности наблюдения неоднородностей намагниченности на поверхности тонких магнитных пленок в Ta/CoFeB/MgO/CoFeB/Ta многослойных структурах

This work presents the results of the study of non-uniformly magnetized regions on the surface of thin magnetic films in multilayer magnetic tunnel junction (MTJ) structure Ta/CoFeB/MgO/CoFeB/Ta ob- served by highly sensitive magnetic force microscopy (MFM) probes. The micromagnetic simulation of the magnetization dynamics in CoFeB magnetic layer after the application of the external magnetic field of 0.5 T is conducted using mumax3 open-source software. The areas of the existence of magnetic vortices and domain walls in CoFeB magnetic film are found where the domain wall thickness was measured by MFM in the nanometer scaleПредставлены результаты исследования неоднородностей намагниченности на поверхности тонких магнитных пленок в структуре многослойного магнитного туннельного перехода (МТП) Ta/CoFeB/MgO/CoFeB/Ta с помощью высокочувствительных зондов МСМ. Проведено микромаг- нитное моделирование магнитной динамики в CoFeB магнитном слое при наведении внешнего магнитного поля величиной 0.5 Тл с использованием программного пакета mumax3. Найдены обла- сти существования магнитных вихрей и доменных стенок в CoFeB магнитной пленки, а также измерены толщины доменных стенок в нанометровом масштаб