Cellular senescence and aging: the role of B-MYB

Cellular senescence is a stable cell cycle arrest, caused by insults, such as: telomere erosion, oncogene activation, irradiation, DNA damage, oxidative stress, and viral infection. Extrinsic stimuli such as cell culture stress can also trigger this growth arrest. Senescence is thought to have evolved as an example of antagonistic pleiotropy, as it acts as a tumor suppressor mechanism during the reproductive age, but can promote organismal aging by disrupting tissue renewal, repair, and regeneration later in life. The mechanisms underlying the senescence growth arrest are broadly considered to involve p16(INK4A) -pRB and p53-p21(CIP1/WAF1/SDI1) tumor suppressor pathways; but it is not known what makes the senescence arrest stable and what the critical downstream targets are, as they are likely to be key to the establishment and maintenance of the senescent state. MYB-related protein B (B-MYB/MYBL2), a member of the myeloblastosis family of transcription factors, has recently emerged as a potential candidate for regulating entry into senescence. Here, we review the evidence which indicates that loss of B-MYB expression has an important role in causing senescence growth arrest. We discuss how B-MYB acts, as the gatekeeper, to coordinate transit through the cell cycle, in conjunction with the multivulval class B (MuvB) complex and FOXM1 transcription factors. We also evaluate the evidence connecting B-MYB to the mTOR nutrient signaling pathway and suggest that inhibition of this pathway leading to an extension of healthspan may involve activation of B-MYB

Socioeconomic inequality of cancer mortality in the United States: a spatial data mining approach

BACKGROUND: The objective of this study was to demonstrate the use of an association rule mining approach to discover associations between selected socioeconomic variables and the four most leading causes of cancer mortality in the United States. An association rule mining algorithm was applied to extract associations between the 1988–1992 cancer mortality rates for colorectal, lung, breast, and prostate cancers defined at the Health Service Area level and selected socioeconomic variables from the 1990 United States census. Geographic information system technology was used to integrate these data which were defined at different spatial resolutions, and to visualize and analyze the results from the association rule mining process. RESULTS: Health Service Areas with high rates of low education, high unemployment, and low paying jobs were found to associate with higher rates of cancer mortality. CONCLUSION: Association rule mining with geographic information technology helps reveal the spatial patterns of socioeconomic inequality in cancer mortality in the United States and identify regions that need further attention

Estimating the effect of multiple imputation on incomplete longitudinal data with application to a randomized clinical study

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Prevalence of undiagnosed airflow obstruction among people with a history of smoking in a primary care setting

Purpose: The purpose of this study was to define the prevalence of undiagnosed airflow obstruction (AO) among subjects with a history of smoking but no previous diagnosis of chronic lung disease. The finding of AO likely represents diagnosis of chronic obstructive pulmonary disease. Patients: People aged ≥30 years with a history of smoking who attended public outpatient clinics for primary care services were included in this study. Methods: A cross-sectional survey in five clinics in Hong Kong using the Breathlessness, Cough, and Sputum Scale, the Lung Function Questionnaire, and office spirometry was conducted. Results: In total, 731 subjects (response rate =97.9%) completed the questionnaires and spiro­metry tests. Most of the subjects were men (92.5%) in the older age group (mean age =62.2 years; standard deviation =11.7). Of the 731 subjects, 107 had AO, giving a prevalence of 14.6% (95% confidence interval =12.1–17.2); 45 subjects with AO underwent a postbronchodilator test. By classifying the severity of chronic obstructive pulmonary disease using the Global Initiative for Chronic Obstructive Lung Disease, 27 (60%) were considered to be in mild category and 18 (40%) in moderate category. None of them belonged to the severe or very severe category. The total score of Lung Function Questionnaire showed that majority of the subjects with AO also had chronic cough, wheezing attack, or breathlessness, although most did not show any acute respiratory symptoms in accordance with the Breathlessness, Cough, and Sputum Scale. Diagnosis of AO was positively associated with the number of years of smoking (odds ratio =1.044, P=0.035) and being normal or underweight (odds ratio =1.605, P=0.046). It was negatively associated with a history of hypertension (odds ratio =0.491, P=0.003). Conclusion: One-seventh of smokers have undiagnosed AO. Spirometry screening of smokers should be considered in order to diagnose AO at an early stage, with an emphasis on smoking cessation.published_or_final_versio

A novel p70 S6 kinase-microRNA biogenesis axis mediates multicellular spheroid formation in ovarian cancer progression

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Up-regulation of aldose reductase activity in cultured mesangial cells overexpressing human aldose reductase gene is associated with increased TGF-beta1 and collagen IV expression

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Left ventricular torsional mechanics and myocardial iron load in beta-thalassaemia major: a potential role of titin degradation

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Dynamic dyssynchrony and impaired contractile reserve of the left ventricle in beta-thalassaemia major: an exercise echocardiographic study

BACKGROUND: Performance of the left ventricle during exercise stress in thalassaemia patients is uncertain. We aimed to explore the phenomenon of dynamic dyssynchrony and assess contractile reserve in patients with beta-thalassaemia major and determine their relationships with myocardial iron load. METHODS AND RESULTS: Thirty-two thalassaemia patients (16 males), aged 26.8+/-6.9 years, without heart failure and 17 healthy controls were studied. Their left ventricular (LV) volumes, ejection fraction, systolic dyssynchrony index (SDI), and myocardial acceleration during isovolumic LV contraction (IVA) were determined at rest and during submaximal bicycle exercise testing using 3-dimensional and tissue Doppler echocardiography. Myocardial iron load as assessed by T2* cardiac magnetic resonance in patients were further related to indices of LV dyssynchrony and contractile reserve. At rest, patients had significantly greater LV SDI (p4.6%, control+2SD) increased from baseline 25% to 84% in patients. Delta SDI(exercise-baseline) correlated with exercise-baseline differences in LV ejection fraction (p<0.001) and stroke volume (p = 0.006). Compared with controls, patients had significantly less exercise-induced increase in LV ejection fraction, cardiac index, and IVA (interaction, all p<0.05) and had impaired contractile reserve as reflected by the gentler IVA-heart rate slope (p = 0.018). Cardiac T2* in patients correlated with baseline LV SDI (r = -0.44, p = 0.011) and IVA-heart rate slope (r = 0.36, p = 0.044). CONCLUSIONS: Resting LV dyssynchrony is associated with myocardial iron load. Exercise stress further unveils LV dynamic dyssynchrony and impaired contractile reserve in patients with beta-thalassaemia major.published_or_final_versio

Biofilter aquaponic system for nutrients removal from fresh market wastewater

Aquaponics is a significant wastewater treatment system which refers to the combination of conventional aquaculture (raising aquatic organism) with hydroponics (cultivating plants in water) in a symbiotic environment. This system has a high ability in removing nutrients compared to conventional methods because it is a natural and environmentally friendly system (aquaponics). The current chapter aimed to review the possible application of aquaponics system to treat fresh market wastewater with the intention to highlight the mechanism of phytoremediation occurs in aquaponic system. The literature revealed that aquaponic system was able to remove nutrients in terms of nitrogen and phosphorus

Coffee bean extracts rich and poor in kahweol both give rise to elevation of liver enzymes in healthy volunteers

BACKGROUND: Coffee oil potently raises serum cholesterol levels in humans. The diterpenes cafestol and kahweol are responsible for this elevation. Coffee oil also causes elevation of liver enzyme levels in serum. It has been suggested that cafestol is mainly responsible for the effect on serum cholesterol levels and that kahweol is mainly responsible for the effect on liver enzyme levels. The objective of this study was to investigate whether coffee oil that only contains a minute amount of kahweol indeed does not cause elevation of liver enzyme levels. METHODS: The response of serum alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) to Robusta coffee oil (62 mg/day cafestol, 1.6 mg/day kahweol) was measured in 18 healthy volunteers. RESULTS: After nine days one subject was taken off Robusta oil treatment due to an ALAT level of 3.6 times the upper limit of normal (ULN). Another two subjects stopped treatment due to other reasons. After 16 days another two subjects were taken off Robusta oil treatment. One of those subjects had levels of 5.8 ULN for ALAT and 2.0 ULN for ASAT; the other subject had an ALAT level of 12.4 ULN and an ASAT level of 4.7 ULN. It was then decided to terminate the study. The median response of subjects to Robusta oil after 16 days was 0.27 ULN (n = 15, 25(th),75(th )percentile: 0.09;0.53) for ALAT and 0.06 ULN (25(th),75(th )percentile -0.06;0.22) for ASAT. CONCLUSIONS: We conclude that the effect on liver enzyme levels of coffee oil containing hardly any kahweol is similar to that of coffee oil containing high amounts of kahweol. Therefore it is unlikely that kahweol is the component of coffee oil that is responsible for the effect. Furthermore, we conclude that otherwise unexplained elevation of liver enzyme levels observed in patients might be caused by a switch from consumption of filtered coffee to unfiltered coffee