102 research outputs found
Perceptions and practice of personal protective behaviors to prevent COVID-19 transmission in the G7 nations
Introduction: To combat the transmission of COVID-19, countries have endorsed a series of non-pharmaceutical measures. We evaluated the practice and perceptions of personal protective measures and social distancing across the G7 countries. Methods: Data were collected during 19–21 March 2020, from 7005 of Kantar’s online panelists aged >16 years across the G7 countries: Canada, France, Great Britain, Germany, Italy, Japan, and the United States. Data were post-stratified and weighted to match population distributions of the respective countries. Descriptive and multivariable analyses were conducted in late March 2020. Results: Males (vs females) and those less educated (vs college graduates) were less likely to practice personal protective measures and social distancing. Younger adults were also less likely to practice social distancing (vs adults >65 years old). Respondents who expressed concern about the impact of COVID-19 on their health, income or education had higher odds of practicing personal protective measures (AOR=2.81, 1.74, and 1.54, respectively) and social distancing (AOR=3.18, 1.68, and 1.89, respectively) compared to those who did not. Those who perceived precautionary measures as highly effective were also more likely to practice personal protective measures (AOR=2.05) and social distancing (AOR=3.99) compared to those who perceived them as ineffective. Conclusions: Concerns about COVID-19 and perceived effectiveness of precautionary measures strongly predict practice of protective measures, regardless of the types of behaviors. Population-wide interventions should focus on ensuring increased adherence and tailoring communications to groups that are less likely to practice protective behaviors
Interaction of Iron II Complexes with B-DNA. Insights from Molecular Modeling, Spectroscopy, and Cellular Biology
We report the characterization of the interaction between B-DNA and three terpyridin iron II complexes. Relatively long time-scale molecular dynamics is used in order to characterize the stable interaction modes. By means of molecular modeling and UV-vis spectroscopy, we prove that they may lead to stable interactions with the DNA duplex. Furthermore, the presence of larger π-conjugated moieties also leads to the appearance of intercalation binding mode. Non-covalent stabilizing interactions between the iron complexes and the DNA are also characterized and evidenced by the analysis of the gradient of the electronic density. Finally, the structural deformations induced on the DNA in the different binding modes are also evidenced. The synthesis and chemical characterization of the three complexes is reported, as well as their absorption spectra in presence of DNA duplexes to prove the interaction with DNA. Finally, their effects on human cell cultures have also been evidenced to further enlighten their biological effects
Public perspective on the governmental response, communication and trust in the governmental decisions in mitigating COVID-19 early in the pandemic across the G7 countries
The COVID-19 pandemic poses a threat to global health and security inciting governments with the responsibility to respond with measures that ensure the health and safety of their communities. We assessed public attitudes towards governmental actions to combat the COVID-19 pandemic in the G7 countries. Data were collected during 19th–21st March 2020, from 7005 Kantar's online panelists aged >16 years across the G7 countries: Canada, France, Great Britain, Germany, Italy, Japan, and the United States. Data were post-stratified and weighted to match population distributions of the respective countries. Descriptive and multivariable analyses were conducted. Amongst the G7, Japan had the lowest level of approval of governmental response to the pandemic, rating governmental communication as good, and trusting governmental decisions (35.0%, 33.6%, and 38.0%, respectively), followed by the U.S. (52.9%, 64.6%, and 59.9%, respectively). Understanding of which measures one can personally take to help limit the spread of the coronavirus was significantly associated with approving governmental response (aOR = 2.88), rating government communication as good (aOR = 2.70) and trust in future governmental decisions (aOR = 2.73). Those who reported government/politicians and friends/family as their most trusted information source were more likely to report approval, higher rating, and/or trust toward governmental actions. Public attitudes towards governmental actions against COVID-19 varied substantially across the G7 countries and were associated with the understanding of measures and source of information that respondents most trusted. Timely and accurate communication is essential to enhance public engagement to control the COVID-19 pandemic
Predictors of progression free survival, overall survival and early cessation of chemotherapy in women with potentially platinum sensitive (PPS) recurrent ovarian cancer (ROC) starting third or subsequent line(> 3) chemotherapy – the GCIG Symptom Benefit Study (SBS)
Background:
Potentially platinum sensitive recurrent ovarian cancer (PPS ROC) is defined by a platinum-free interval of >6 months, and usually treated with platinum-based chemotherapy with variable response and benefit in women who have had 3 or more lines of chemotherapy(≥3). We identified baseline characteristics (health-related quality of life[HRQL] and clinicopathological factors), associated with PFS, OS and early progression (within 8 weeks). The goal is to improve patient selection for chemotherapy based on a nomogram predicting PFS.
Methods:
HRQL was assessed with EORTC QLQ-C30/QLQ-OV28. Associations with PFS and OS were assessed with Cox proportional hazards regression. Variables significant in univariable analysis were included in multivariable analyses using backward elimination to select those significant. Associations with stopping chemotherapy early were assessed with logistic regression.
Results:
378 women were enrolled, with median(m)OS and PFS of 16.6 months and 5.3 months, respectively. The majority had ECOGPS 0–1. Chemotherapy was stopped early in 45/378 participants (12%); with mOS 3.4 months (95% CI: 1.7–7.2). Physical function(PF), role function(RF), cognitive function(CF), social function(SF), Global Health Status(GHS) and abdominal/GI symptoms(AGIS) were significant univariable predictors of PFS(p < 0.030). SF remained significant after adjusting for clinicopathological factors; p = 0.03. PF, RF, CF, SF, GHS and AGIS were significant univariable predictors of OS (p < 0.007); PF, RF, SF and GHS remained significant predictors of OS in multivariable models; p < 0.007. Poor baseline PF and GHS were significant univariable predictors of stopping chemotherapy early (p < 0.007) but neither remained significant after adjusting for clinicopathological factors.
Conclusion:
Baseline HRQL is simple to measure, is predictive of PFS and OS and when used in conjunction with clinicopathological prognostic factors, can assist with clinical decision making and treatment recommendations for women with PPSROC≥3
Adaptive Multidimensional Modeling with Applications in Scientific Computing
No abstract availabl
Developing the Human, Material, and Structural Aspects of Infrastructure for Collaborative Curriculum Design:Lessons Learned
Genetic dissection of early endosomal recycling highlights a TORC1-independent role for Rag GTPases
Endocytosed cell surface membrane proteins rely on recycling pathways for their return to the plasma membrane. Although endosome-to-plasma membrane recycling is critical for many cellular processes, much of the required machinery is unknown. We discovered that yeast has a recycling route from endosomes to the cell surface that functions efficiently after inactivation of the sec7-1 allele of Sec7, which controls transit through the Golgi. A genetic screen based on an engineered synthetic reporter that exclusively follows this pathway revealed that recycling was subject to metabolic control through the Rag GTPases Gtr1 and Gtr2, which work downstream of the exchange factor Vam6. Gtr1 and Gtr2 control the recycling pathway independently of TORC1 regulation through the Gtr1 interactor Ltv1. We further show that the early-endosome recycling route and its control though the Vam6 > Gtr1/Gtr2 > Ltv1 pathway plays a physiological role in regulating the abundance of amino acid transporters at the cell surface
Damaged DNA Binding Protein 2 Plays a Role in Breast Cancer Cell Growth
The Damaged DNA binding protein 2 (DDB2), is involved in nucleotide excision repair as well as in other biological processes in normal cells, including transcription and cell cycle regulation. Loss of DDB2 function may be related to tumor susceptibility. However, hypothesis of this study was that DDB2 could play a role in breast cancer cell growth, resulting in its well known interaction with the proliferative marker E2F1 in breast neoplasia. DDB2 gene was overexpressed in estrogen receptor (ER)-positive (MCF-7 and T47D), but not in ER-negative breast cancer (MDA-MB231 and SKBR3) or normal mammary epithelial cell lines. In addition, DDB2 expression was significantly (3.0-fold) higher in ER-positive than in ER-negative tumor samples (P = 0.0208) from 16 patients with breast carcinoma. Knockdown of DDB2 by small interfering RNA in MCF-7 cells caused a decrease in cancer cell growth and colony formation. Inversely, introduction of the DDB2 gene into MDA-MB231 cells stimulated growth and colony formation. Cell cycle distribution and 5 Bromodeoxyuridine incorporation by flow cytometry analysis showed that the growth-inhibiting effect of DDB2 knockdown was the consequence of a delayed G1/S transition and a slowed progression through the S phase of MCF-7 cells. These results were supported by a strong decrease in the expression of S phase markers (Proliferating Cell Nuclear Antigen, cyclin E and dihydrofolate reductase). These findings demonstrate for the first time that DDB2 can play a role as oncogene and may become a promising candidate as a predictive marker in breast cancer
Compartmentation of Redox Metabolism in Malaria Parasites
Malaria, caused by the apicomplexan parasite Plasmodium, still represents a major threat to human health and welfare and leads to about one million human deaths annually. Plasmodium is a rapidly multiplying unicellular organism undergoing a complex developmental cycle in man and mosquito – a life style that requires rapid adaptation to various environments. In order to deal with high fluxes of reactive oxygen species and maintain redox regulatory processes and pathogenicity, Plasmodium depends upon an adequate redox balance. By systematically studying the subcellular localization of the major antioxidant and redox regulatory proteins, we obtained the first complete map of redox compartmentation in Plasmodium falciparum. We demonstrate the targeting of two plasmodial peroxiredoxins and a putative glyoxalase system to the apicoplast, a non-photosynthetic plastid. We furthermore obtained a complete picture of the compartmentation of thioredoxin- and glutaredoxin-like proteins. Notably, for the two major antioxidant redox-enzymes – glutathione reductase and thioredoxin reductase – Plasmodium makes use of alternative-translation-initiation (ATI) to achieve differential targeting. Dual localization of proteins effected by ATI is likely to occur also in other Apicomplexa and might open new avenues for therapeutic intervention
Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants
The relative concentrations of ions and solutes inside cells are actively maintained by several classes of transport proteins, in many cases against their concentration gradient. These transport processes, which consume a large portion of cellular energy, must be constantly regulated. Many structurally distinct families of channels, carriers, and pumps have been characterized in considerable detail during the past decades and defects in the function of some of these proteins have been linked to a growing list of human diseases. The dynamic regulation of the transport proteins present at the cell surface is vital for both normal cellular function and for the successful adaptation to changing environments. The composition of proteins present at the cell surface is controlled on both the transcriptional and post-translational level. Post-translational regulation involves highly conserved mechanisms of phosphorylation- and ubiquitylation-dependent signal transduction routes used to modify the cohort of receptors and transport proteins present under any given circumstances. In this review, we will summarize what is currently known about one facet of this regulatory process: the endocytic regulation of alkali metal transport proteins. The physiological relevance, major contributors, parallels and missing pieces of the puzzle in mammals, yeast and plants will be discussed.This work was supported by grant BFU2011-30197-C03-03 from the Ministerio de Ciencia e Innovacion (Spain). V.L.-T. is supported by a fellowship from the Universidad Politecnica de Valencia. C. P. is supported by a fellowship from the Consejo Superior de Investigaciones Cientificas (Spain).Mulet Salort, JM.; Llopis Torregrosa, V.; Primo Planta, C.; Marques Romero, MC.; Yenush, L. (2013). 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