CLOCK in Breast Tumorigenesis: Evidence From Genetic, Epigenetic, and Transcriptional Profiling Analyses

As transcriptional regulators, the genes responsible for maintaining circadian rhythm exert influence in a variety of biological processes. Recently, it has been suggested that the core circadian genes may play a role in breast tumorigenesis, possibly by influencing hormone regulation or other cancer-relevant pathways. Here, we examine the role of the central circadian regulator CLOCK in breast cancer by conducting a genetic and epigenetic association study, as well as transcriptional profiling arrays and a pathway-based network analysis. Significant associations were detected between CLOCK tagging SNPs and breast cancer risk, with apparent effect modification by ER/PR status. Furthermore, hypermethylation in the CLOCK promoter was found to reduce breast cancer risk, and these findings were corroborated by publicly available tissue array data, which showed lower levels of CLOCK expression in healthy controls relative to normal or tumor tissue from breast cancer patients. Finally, we silenced CLOCK in vitro and performed a whole genome expression microarray and pathway analysis, which identified a cancer-relevant network of transcripts with altered expression following CLOCK gene knockdown. These findings support the hypothesis that circadian genes may be relevant for tumorigenesis, and suggest that circadian gene variants may represent a novel panel of breast cancer susceptibility biomarkers

Adverse health effects of nighttime lighting: comments on american medical association policy statement.

The American Medical Association House of Delegates in June of 2012 adopted a policy statement on nighttime lighting and human health. This major policy statement summarizes the scientific evidence that nighttime electric light can disrupt circadian rhythms in humans and documents the rapidly advancing understanding from basic science of how disruption of circadian rhythmicity affects aspects of physiology with direct links to human health, such as cell cycle regulation, DNA damage response, and metabolism. The human evidence is also accumulating, with the strongest epidemiologic support for a link of circadian disruption from light at night to breast cancer. There are practical implications of the basic and epidemiologic science in the form of advancing lighting technologies that better accommodate human circadian rhythmicity

Performance of point-of-care HbA1c test devices: implications for use in clinical practice – a systematic review and meta-analysis

Regular monitoring of glycated hemoglobin subfraction A1c (HbA1c) in people with diabetes and treatment with glucose-lowering medications to improve glycaemic control can reduce the risk of developing complications [1]. In 2011, a World Health Organization consultation concluded that HbA1cat a threshold of 6.5% (48 mmol/mol) can be used as a diagnostic test for diabetes [2]. HbA1c monitoring often requires the patient to attend the health center twice: once to have blood taken and then returning to get test results and receive adjustments to medication. Point-of-care (POC) analysers are bench-top instruments that use a finger-prick blood sample and are designed for use in a treatment room or at the bed-side. They provide a test result within a few minutes allowing clinical decisions and medication changes to take place immediately. The suitability of many of these devices for the accurate measurement of HbA1c has been questioned, with some POC HbA1c test devices reported not to meet accepted accuracy and precision criteria [3]. Ideal imprecision goals for HbA1c should be coefficient of variation (CV) of <2% for HbA1c reported in % units (or <3% in SI units, mmol/mol) [4], [5], [6]. Most evaluations of POC HbA1c devices have taken place in laboratory settings [7], [8]; fewer studies have assessed device performance in a POC setting or with clinicians performing the tests [9], [10]. The only published review that has attempted to combine data from accuracy studies identified five studies covering three devices and compared correlation coefficients [11]. Systematically reporting and pooling data estimates of bias and precision between POC HbA1c devices and laboratory measurements would enable end users to assess which analysers best meet their analytical performance needs. This may be of particular importance for clinicians in primary care settings where much of the management of diabetes patients takes place. The comparison of accuracy between devices over the entire therapeutic range would need to be carried out by combining data on measurement error (bias) between POC and laboratory tests [12]. The aim of this study was to compare accuracy and precision of POC HbA1c devices with the local laboratory method based on data from published studies and discuss the clinical implications of the findings

Transitions between turbulent states in rotating Rayleigh-Benard convection

Weakly-rotating turbulent Rayleigh-Benard convection was studied experimentally and numerically. With increasing rotation and large enough Rayleigh number an abrupt transition from a turbulent state with nearly rotation-independent heat transport to another turbulent state with enhanced heat transfer is observed at a critical inverse Rossby number $1/Ro_c \simeq 0.4$. Whereas for $1/Ro < 1/Ro_c$ the strength of the large-scale convection-roll is either enhanced or essentially unmodified depending on parameters, its strength is increasingly diminished beyond $1/Ro_c$ where it competes with Ekman vortices that cause vertical fluid transport and thus heat-transfer enhancement.Comment: 5 pages, 4 figure

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability