Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome

Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomeric antisense oligonucleotides (tASOs) prevents full DDR activation and premature cellular senescence in various HGPS cell systems, including HGPS patient fibroblasts. We also show in vivo that tASO treatment significantly enhances skin homeostasis and lifespan in a transgenic HGPS mouse model. In summary, our results demonstrate an important role for telomeric DDR activation in HGPS progeroid detrimental phenotypes in vitro and in vivo

Sigma-2 receptors as a biomarker of proliferation in solid tumours

Over the past several years, our group has provided considerable evidence that the expression of sigma-2 (σ2) receptors may serve as a biomarker of tumour cell proliferation. In these in vitro studies, σ2receptors were expressed 8–10 times more in proliferative (P) tumour cells than in quiescent (Q) tumour cells, and the extent and kinetics of their expression were independent of a number of biological, physiological and environmental factors often found in solid tumours. Moreover, the expression of σ2receptors followed both the population growth kinetics when Q-cells were recruited into the P-cell compartment and the proliferative status of human breast tumour cells treated with cytostatic concentrations of tamoxifen. However, these in vitro studies may or may not be indicative of what might occur in solid tumours. In the present study, the σ2receptor P:Q ratio was determined for the cells from subcutaneous 66 (diploid) and 67 (aneuploid) tumours grown in female nude mice. The σ2receptor P:Q ratio of the 66 tumours was 10.6 compared to the σ2receptor P:Q ratio of 9.5 measured for the 66 tissue culture model. The σ2receptor P:Q ratio of the 67 tumours was 4.5 compared to the σ2receptor P:Q ratio of ≈ 8 measured for the 67 tissue culture model. The agreement between the solid tumour and tissue culture data indicates that: (1) the expression of σ2receptors may be a reliable biomarker of the proliferative status of solid tumours and (2) radioligands with both high affinity and high selectivity for σ2receptors may have the potential to non-invasively assess the proliferative status of human solid tumours using imaging techniques such as positron emission tomography or single-photon emission computerized tomography. © 2000 Cancer Research Campaig

Vibrational dynamics of a two-dimensional microgranular crystal

We study the dynamics of an ordered hexagonal monolayer of polystyrene microspheres adhered to a glass substrate coated with a thin aluminum layer. A laser-induced transient grating technique is employed to generate and detect three types of acoustic modes across the entire Brillouin zone in the Γ−K direction: low-frequency contact-based modes of the granular monolayer, high-frequency modes originating from spheroidal vibrations of the microspheres, and surface Rayleigh waves. The dispersion relation of contact-based and spheroidal modes indicates that they are collective modes of the microgranular crystal controlled by particle-particle contacts. We observe a spheroidal resonance splitting caused by the symmetry breaking due to the substrate, as well as an avoided crossing between the Rayleigh and spheroidal modes. The measurements are found to be in agreement with our analytical model.United States. Department of Energy (Grant DE-FG02-00ER15087)National Science Foundation (U.S.) (Grant CHE-1111557

Changes in salivary estradiol predict changes in women’s preferences for vocal masculinity

Although many studies have reported that women’s preferences for masculine physical characteristics in men change systematically during the menstrual cycle, the hormonal mechanisms underpinning these changes are currently poorly understood. Previous studies investigating the relationships between measured hormone levels and women’s masculinity preferences tested only judgments of men’s facial attractiveness. Results of these studies suggested that preferences for masculine characteristics in men’s faces were related to either women’s estradiol or testosterone levels. To investigate the hormonal correlates of within-woman variation in masculinity preferences further, here we measured 62 women’s salivary estradiol, progesterone, and testosterone levels and their preferences for masculine characteristics in men’s voices in five weekly test sessions. Multilevel modeling of these data showed that changes in salivary estradiol were the best predictor of changes in women’s preferences for vocal masculinity. These results complement other recent research implicating estradiol in women’s mate preferences, attention to courtship signals, sexual motivation, and sexual strategies, and are the first to link women’s voice preferences directly to measured hormone levels

Changes in salivary estradiol predict changes in women’s preferences for vocal masculinity

Although many studies have reported that women’s preferences for masculine physical characteristics in men change systematically during the menstrual cycle, the hormonal mechanisms underpinning these changes are currently poorly understood. Previous studies investigating the relationships between measured hormone levels and women’s masculinity preferences tested only judgments of men’s facial attractiveness. Results of these studies suggested that preferences for masculine characteristics in men’s faces were related to either women’s estradiol or testosterone levels. To investigate the hormonal correlates of within-woman variation in masculinity preferences further, here we measured 62 women’s salivary estradiol, progesterone, and testosterone levels and their preferences for masculine characteristics in men’s voices in five weekly test sessions. Multilevel modeling of these data showed that changes in salivary estradiol were the best predictor of changes in women’s preferences for vocal masculinity. These results complement other recent research implicating estradiol in women’s mate preferences, attention to courtship signals, sexual motivation, and sexual strategies, and are the first to link women’s voice preferences directly to measured hormone levels

Effect of ploidy, recruitment, environmental factors, and tamoxifen treatment on the expression of sigma-2 receptors in proliferating and quiescent tumour cells

Recently, we demonstrated that sigma-2 receptors may have the potential to be a biomarker of tumour cell proliferation (Mach et al (1997) Cancer Res57: 156–161). If sigma-2 receptors were a biomarker of tumour cell proliferation, they would be amenable to detection by non-invasive imaging procedures, thus eliminating many of the problems associated with the flow cytometric measures of tumour cell proliferation presently used in the clinic. To be a good biomarker of tumour cell proliferation, the expression of sigma-2 receptors must be essentially independent of many of the biological, physiological, and/or environmental properties that are found in solid tumours. In the investigation reported here, the mouse mammary adenocarcinoma lines, 66 (diploid) and 67 (aneuploid), 9L rat brain tumour cells, and MCF-7 human breast tumour cells were used to study the extent and kinetics of expression of sigma-2 receptors in proliferative (P) and quiescent (Q) tumour cells as a function of species, cell type, ploidy, pH, nutrient depletion, metabolic state, recruitment from the Q-cell compartment to the P-cell compartment, and treatment with tamoxifen. In these experiments, the expression of sigma-2 receptors solely reflected the proliferative status of the tumour cells. None of the biological, physiological, or environmental properties that were investigated had a measurable effect on the expression of sigma-2 receptors in these model systems. Consequently, these data suggest that the proliferative status of tumours and normal tissues can be non-invasively assessed using radiolabelled ligands that selectively bind sigma-2 receptors. © 1999 Cancer Research Campaig

Integrating team science into interdisciplinary graduate education: an exploration of the SESYNC Graduate Pursuit

Complex socio-environmental challenges require interdisciplinary, team-based research capacity. Graduate students are fundamental to building such capacity, yet formal opportunities for graduate students to develop these capacities and skills are uncommon. This paper presents an assessment of the Graduate Pursuit (GP) program, a formal interdisciplinary team science graduate research and training program administered by the National Socio-Environmental Synthesis Center (SESYNC). Quantitative and qualitative assessment of the program’s first cohort revealed that participants became significantly more comfortable with interdisciplinary research and team science approaches, increased their capacity to work across disciplines, and were enabled to produce tangible research outcomes. Qualitative analysis of four themes—(1) discipline, specialization, and shared purpose, (2) interpersonal skills and personality, (3) communication and teamwork, and (4) perceived costs and benefits—encompass participants’ positive and negative experiences and support findings from past assessments. The findings also identify challenges and benefits related to individual personality traits and team personality orientation, the importance of perceiving a sense of autonomy and independence, and the benefit of graduate training programs independent of the university and graduate program environment

Readability of American Online Patient Education Materials in Urologic Oncology: A Need for Simple Communication

To determine readability levels of reputable cancer and urologic websites addressing bladder, prostate, kidney and testicular cancers

Gender Differences in Compensation, Job Satisfaction and Other Practice Patterns in Urology

The proportion of women in urology has increased from <0.5% in 1981 to 10% today. Furthermore, 33% of students matching in urology are now female. This analysis sought to characterize the female workforce in urology in comparison to men with regard to income, workload, and job satisfaction