A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity.

The Mre11-Rad50-Nbs1 complex (MRN) is important for repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). The endonuclease activity of MRN is critical for resecting 5'-ended DNA strands at DSB ends, producing 3'-ended single-strand DNA, a prerequisite for HR. This endonuclease activity is stimulated by Ctp1, the Schizosaccharomyces pombe homolog of human CtIP. Here, with purified proteins, we show that Ctp1 phosphorylation stimulates MRN endonuclease activity by inducing the association of Ctp1 with Nbs1. The highly conserved extreme C terminus of Ctp1 is indispensable for MRN activation. Importantly, a polypeptide composed of the conserved 15 amino acids at the C terminus of Ctp1 (CT15) is sufficient to stimulate Mre11 endonuclease activity. Furthermore, the CT15 equivalent from CtIP can stimulate human MRE11 endonuclease activity, arguing for the generality of this stimulatory mechanism. Thus, we propose that Nbs1-mediated recruitment of CT15 plays a pivotal role in the activation of the Mre11 endonuclease by Ctp1/CtIP.

Affordability of cigarettes in ten Southeastern European countries between 2008 and 2019.

BACKGROUND: The empirical evidence shows that tobacco consumption is strongly associated with its affordability. The nominal growth in tobacco prices imposed by taxation should exceed or at least keep pace with nominal income growth, ensuring that tobacco products become less affordable over time. No analysis covering affordability issues in the Southeastern European (SEE) region has been conducted prior to this research. OBJECTIVES: The study aims to examine trends in cigarette affordability in ten selected SEE countries over the period 2008-2019 and the impact of affordability on the consumption of cigarettes. On the policy side, it aims to support conducting of more effective evidence-based policy of tobacco taxation. METHODS: The relative income price of cigarettes and the tobacco affordability index are used as affordability measures. The panel regression was run to estimate the impact of affordability measures and other covariates on cigarette consumption. RESULTS: The affordability of cigarettes in the selected SEE countries has decreased on average but showed different patterns over the observed period. A decline in affordability has been more dynamic in Western Balkan (non-EU members) countries and low-and-middle-income countries within the SEE region. Econometric estimation confirms affordability as the main determinant of tobacco consumption, indicating that a decline in affordability considerably reduces tobacco consumption. CONCLUSIONS: Despite the evidence, affordability is still widely ignored by SEE policymakers when designing national tobacco taxation policies. Policymakers should be aware of the risk that future increases in cigarette prices could lag behind real income growth, making tax policy less effective at reducing consumption. Reducing affordability should be the paramount consideration in designing effective tobacco taxation policies.

Smoking patterns during COVID-19: Evidence from Serbia.

INTRODUCTION: Recent research shows that in many countries, smokers who increased smoking during the COVID-19 pandemic outnumbered those who decreased it, despite higher exposure to COVID-19 severity and death. In this study, we compared changes in smoking behavior in the initial and later stages of the pandemic and factors associated with lower smoking intensity. METHODS: We conducted two survey rounds on representative samples, the first in the initial stage of the pandemic (11-19 May 2020) and the second in the latter stage (4-11 June 2021), in Serbia. Multinomial logistic regression was run to estimate associations between smokers' characteristics and lower smoking intensity. In contrast to most studies that assess psychological factors affecting smoking in the pandemic, we focused on factual determinants of the change in smoking intensity. RESULTS: The share of smokers who claimed to smoke more increased significantly, from 22.7% in May 2020 to 35.2% in June 2021. The share of smokers who reported a decrease in smoking only slightly increased, from 11.7% to 13.3%. The persistence of the pandemic considerably increased intentions to cease smoking, from 26.3% to 40%. Higher education (adjusted odds ratio, AOR=2.11; 95% CI: 1.08-4.13), income fall (AOR=2.14; 95% CI: 1.11-4.11), occasional smoking (AOR=4.24; 95% CI: 2.26-7.96) and recovery from COVID-19 (AOR=2.38; 95% CI: 1.23-4.60) increased the odds to reduce smoking during the pandemic. CONCLUSIONS: Most smokers are unaware that consuming tobacco products increases exposure to health risks related to COVID-19, but those who get coronavirus infected tend to reduce smoking. This research highlights that tobacco control policy needs to be more proactive in creating public campaigns which demonstrate the severity of COVID-19 impact on smokers' health. Such campaigns should mainly target those groups of smokers who are less able to curb their smoking intensity.

Modified Biochanin A Release from Dual pH- and Thermo-Responsive Copolymer Hydrogels.

The temperature- and pH-responsive poly(N-isopropylacrylamide-co-acrylic acid), p(NIPAM-co-AA), copolymer was synthesized by free radical polymerization and examined as a carrier for modified release of biochanin A. Biochanin A is a biologically active methoxylated isoflavone which exhibits estrogenic and other pharmacological activities. Due to its poor aqueous solubility and extensive first-pass metabolism, biochanin A has low bioavailability. The aim of this work was to incorporate biochanin A into the synthesized p(NIPAM-co-AA) copolymer and to examine its release at the body temperature and pH values that correspond to pH values of vaginal and rectal cavities. The amount of released biochanin A was monitored by the ultra-visible spectroscopy (UV-Vis) method. The structure of synthesized p(NIPAM-co-AA) copolymer and copolymer with incorporated biochanin A were characterized by using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) methods. The content of residual monomers in the synthesized copolymer was analyzed by using the high-pressure liquid chromatography (HPLC) method. The swelling behavior of p(NIPAM-co-AA) copolymer was monitored in relation to the temperature and pH values of the surrounding medium. For modelling the process of p(NIPAM-co-AA) copolymer swelling, the full three-level factorial design was applied.