Streptococcus Pneumoniae Secretes Hydrogen Peroxide Leading to DNA Damage and Apoptosis in Lung Cells

Streptococcus pneumoniae is a leading cause of pneumonia and one of the most common causes of death globally. The impact of S. pneumoniae on host molecular processes that lead to detrimental pulmonary consequences is not fully understood. Here, we show that S. pneumoniae induces toxic DNA double-strand breaks (DSBs) in human alveolar epithelial cells, as indicated by ataxia telangiectasia mutated kinase (ATM)-dependent phosphorylation of histone H2AX and colocalization with p53-binding protein (53BP1). Furthermore, results show that DNA damage occurs in a bacterial contact-independent fashion and that Streptococcus pyruvate oxidase (SpxB), which enables synthesis of H[subscript 2]O[subscript 2], plays a critical role in inducing DSBs. The extent of DNA damage correlates with the extent of apoptosis, and DNA damage precedes apoptosis, which is consistent with the time required for execution of apoptosis. Furthermore, addition of catalase, which neutralizes H[subscript 2]O[subscript 2], greatly suppresses S. pneumoniae-induced DNA damage and apoptosis. Importantly, S. pneumoniae induces DSBs in the lungs of animals with acute pneumonia, and H[subscript 2]O[subscript 2] production by S. pneumoniae in vivo contributes to its genotoxicity and virulence. One of the major DSBs repair pathways is nonhomologous end joining for which Ku70/80 is essential for repair. We find that deficiency of Ku80 causes an increase in the levels of DSBs and apoptosis, underscoring the importance of DNA repair in preventing S. pneumoniae-induced genotoxicity. Taken together, this study shows that S. pneumoniae-induced damage to the host cell genome exacerbates its toxicity and pathogenesis, making DNA repair a potentially important susceptibility factor in people who suffer from pneumonia

Post-activation Performance Enhancement after a Bout of Accentuated Eccentric Loading in Collegiate Male Volleyball Players

The purpose of this study was to investigate the benefit of post-activation performance enhancement (PAPE) after accentuated eccentric loading (AEL) compared to traditional resistance loading (TR). Sixteen male volleyball athletes were divided in AEL and TR group. AEL group performed 3 sets of 4 repetitions (eccentric: 105% of concentric 1RM, concentric: 80% of concentric 1RM) of half squat, and TR group performed 3 sets of 5 repetitions (eccentric & concentric: 85% of 1RM). Countermovement jump (CMJ), spike jump (SPJ), isometric mid-thigh pull (IMTP), and muscle soreness test were administered before (Pre) exercise, and 10 min (10-min), 24 h (24-h), and 48 h (48-h) after exercise. A two-way repeated measures analysis of variance was used to analyze the data. Peak force and rate of development (RFD) of IMTP in AEL group were significantly greater (p 0.05) groups x time. AEL seemed capable to maintain force production in IMTP, but not in CMJ and SPJ. It is recommended the use of accentuated eccentric loading protocols to overcome the fatigue

Supramolecular chemistry enables vat photopolymerization 3D printing of novel water-soluble tablets

Vat photopolymerization has garnered interest from pharmaceutical researchers for the fabrication of personalised medicines, especially for drugs that require high precision dosing or are heat labile. However, the 3D printed structures created thus far have been insoluble, limiting printable dosage forms to sustained-release systems or drug-eluting medical devices which do not require dissolution of the printed matrix. Resins that produce water-soluble structures will enable more versatile drug release profiles and expand potential applications. To achieve this, instead of employing cross-linking chemistry to fabricate matrices, supramolecular chemistry may be used to impart dynamic interaction between polymer chains. In this study, water-soluble drug-loaded printlets (3D printed tablets) are fabricated via digital light processing (DLP) 3DP for the first time. Six formulations with varying ratios of an electrolyte acrylate monomer, [2-(acryloyloxy)ethyl]trimethylammonium chloride (TMAEA), and a co-monomer, 1-vinyl-2-pyrrolidone (NVP), were prepared to produce paracetamol-loaded printlets. 1H NMR spectroscopy analysis confirmed the integration of TMAEA and NVP in the polymer, and residual TMAEA monomers were found to be present only in trace amounts (0.71 - 1.37 %w/w). The apparent molecular mass of the photopolymerised polymer was found to exceed 300,000 Da with hydrodynamic radii of 15 - 20 nm, estimated based on 1H DOSY NMR measurements The loaded paracetamol was completely released from the printlets between 45 minutes to 5 hours. In vivo single-dose acute toxicity studies in rats suggest that the printlets did not cause any tissue damage. The findings reported in this study represent a significant step towards the adoption of vat photopolymerization-based 3DP to produce personalised medicines

Photosynthetic compensation of non-leaf organ stems of the invasive species Sphagneticola trilobata(L.) Pruski at low temperature

Biological invasion is a hot topic in ecological research. Most studies on the physiological mechanisms of plants focus on leaves, but few studies focus on stems. To study the tolerance of invasive plant (Sphagneticola trilobata L.) to low temperature, relevant physiological indicators (including anthocyanin and chlorophyll) in different organs (leaves and stems) were analyzed, using a native species (Sphagneticola calendulacea L.) as the control. The results showed that, upon exposure to low temperature for 15 days, the stems of two Sphagneticola species were markedly reddened, their anthocyanin content increased, chlorophyll and chlorophyll fluorescence parameters decreased, and the accumulation of reactive oxygen species in the stem increased. The percentage increases of antioxidants and total antioxidant capacities in stems were significantly higher in S. trilobata than in S. calendulacea. This showed that S. trilobata had higher cold tolerance in stems while leaves were opposite. To further verify the higher cold tolerance of the stem of S. trilobata, a defoliation experiment was designed. We found that the defoliated stem of S. trilobata reduced anthocyanin accumulation and increased chlorophyll content, while alleviating membrane lipid damage and electrical conductivity, and the defoliated stem still showed an increase in stem diameter and biomass under low temperature. The discovery of the physiological and adaptive mechanisms of the stem of S. trilobata to low temperature will provide a theoretical basis for explaining how S. trilobata maintains its annual growth in South China. This is of great significance for predicting the future spread of cloned and propagated invasive plants.This work was funded by the National Natural Science Foundation of China (31870374) and the National Key R&D Program of China (2017YFC1200105). The study was also supported by the Innovation Project of Graduate School of South China Normal University

MicroRNA-34a Inhibits the Proliferation and Metastasis of Osteosarcoma Cells Both In Vitro and In Vivo

BACKGROUND: MicroRNAs (miRNAs) are a class of endogenously expressed, small noncoding RNAs, which suppress its target mRNAs at the post-transcriptional level. Studies have demonstrated that miR-34a, which is a direct target of the p53 tumor suppressor gene, functions as a tumor suppressor and is associated with the tumor growth and metastasis of various human malignances. However, the role of miR-34a in osteosarcoma has not been totally elucidated. In the present study, the effects of miR-34a on osteosarcoma and the possible mechanism by which miR-34a affected the tumor growth and metastasis of osteosarcoma were investigated. METHODOLOGY/PRINCIPAL FINDING: Over-expression of miR-34a partially inhibited proliferation, migration and invasion of osteosarcoma cells in vitro, as well as the tumor growth and pulmonary metastasis of osteosarcoma cells in vivo. c-Met is a target of miR-34a, and regulates the migration and invasion of osteosarcoma cells. Osteosarcoma cells over-expressing miR-34a exhibited a significant decrease in the expression levels of c-Met mRNA and protein simultaneously. Finally, the results from bioinformatics analysis demonstrated that there were multiple putative targets of miR-34a that may be associated with the proliferation and metastasis of osteosarcoma, including factors in Wnt and Notch signaling pathways. CONCLUSION/SIGNIFICANCE: The results presented in this study demonstrated that over-expression of miR-34a could inhibit the tumor growth and metastasis of osteosarcoma probably through down regulating c-Met. And there are other putative miR-34a target genes beside c-Met which could potentially be key players in the development of osteosarcoma. Since pulmonary metastases are responsible for mortality of patient carrying osteosarcoma, miR-34a may prove to be a promising gene therapeutic agent. It will be interesting to further investigate the mechanism by which miR-34a functions as a tumor suppressor gene in osteosarcoma

Вихретоковый анизотропный термоэлектрический первичный преобразователь лучистого потока

Представлена оригинальная конструкция первичного преобразователя лучистого потока, который может служить основой для создания приемника неселективного излучения с повышенной чувствительностью

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Analyses of pig genomes provide insight into porcine demography and evolution

For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model