Telomerase-Independent Paths to Immortality in Predictable Cancer Subtypes

The vast majority of cancers commandeer the activity of telomerase - the remarkable enzyme responsible for prolonging cellular lifespan by maintaining the length of telomeres at the ends of chromosomes. Telomerase is only normally active in embryonic and highly proliferative somatic cells. Thus, targeting telomerase is an attractive anti-cancer therapeutic rationale currently under investigation in various phases of clinical development. However, previous reports suggest that an average of 10-15% of all cancers lose the functional activity of telomerase and most of these turn to an Alternative Lengthening of Telomeres pathway (ALT). ALT-positive tumours will therefore not respond to anti-telomerase therapies and there is a real possibility that such drugs would be toxic to normal telomerase-utilising cells and ultimately select for resistant cells that activate an ALT mechanism. ALT exploits certain DNA damage response (DDR) components to counteract telomere shortening and rapid trimming. ALT has been reported in many cancer subtypes including sarcoma, gastric carcinoma, central nervous system malignancies, subtypes of kidney (Wilm's Tumour) and bladder carcinoma, mesothelioma, malignant melanoma and germ cell testicular cancers to name but a few. A recent heroic study that analysed ALT in over six thousand tumour samples supports this historical spread, although only reporting an approximate 4% prevalence. This review highlights the various methods of ALT detection, unravels several molecular ALT models thought to promote telomere maintenance and elongation, spotlights the DDR components known to facilitate these and explores why certain tissues are more likely to subvert DDR away from its usually protective functions, resulting in a predictive pattern of prevalence in specific cancer subsets

The Broad-Band Spectrum and Infrared Variability of the Magnetar AXP 1E1048.1-5937

We present photometry of the Anomalous X-ray pulsar 1E1048.1-5937 in the infrared and optical, taken at Magellan and the VLT. The object is detected in the I, J and Ks bands under excellent conditions. We find that the source has varied greatly in its infrared brightness and present these new magnitudes. No correlation is found between the infrared flux and spin-down rate, but the infrared flux and X-ray flux may be anti-correlated. Assuming nominal reddening values, the resultant spectral energy distribution is found to be inconsistent with the only other AXP SED available (for 4U0142+61). We consider the effect of the uncertainty in the reddening to the source on its SED. We find that although both the X-ray and infrared fluxes have varied greatly for this source, the most recent flux ratio is remarkably consistent with what is is found for other AXPs. Finally, we discuss the implications of our findings in the context of the magnetar model.Comment: 21 pages, 5 eps figures. Submitted to Ap

Identifying Gender-Preferred Communication Styles within Online Cancer Communities: A Retrospective, Longitudinal Analysis

Background: The goal of this research is to determine if different gender-preferred social styles can be observed within the user interactions at an online cancer community. To achieve this goal, we identify and measure variables that pertain to each gender-specific social style. Methods and Findings: We perform social network and statistical analysis on the communication flow of 8,388 members at six different cancer forums over eight years. Kruskal-Wallis tests were conducted to measure the difference between the number of intimate (and highly intimate) dyads, relationship length, and number of communications. We determine that two patients are more likely to form an intimate bond on a gender-specific cancer forum (ovarian P = <0.0001, breast P = 0.0089, prostate P = 0.0021). Two female patients are more likely to form a highly intimate bond on a female-specific cancer forum (Ovarian P<0.0001, Breast P<0.01). Typically a male patient communicates with more members than a female patient (Ovarian forum P = 0.0406, Breast forum P = 0.0013). A relationship between two patients is longer on the gender-specific cancer forums than a connection between two members not identified as patients (ovarian forum P = 0.00406, breast forum P = 0.00013, prostate forum P = .0.0003). Conclusion: The high level of interconnectedness among the prostate patients supports the hypothesis that men prefer to socialize in large, interconnected, less-intimate groups. A female patient is more likely to form a highly intimate connection with another female patient; this finding is consistent with the hypothesis that woman prefer fewer, more intimate connections. The relationships of same-gender cancer patients last longer than other relationships; this finding demonstrates homophily within these online communities. Our findings regarding online communication preferences are in agreement with research findings from person-to-person communication preference studies. These findings should be considered when designing online communities as well as designing and evaluating psychosocial and educational interventions for cancer patients

Evaluation of ELISA Screening Test for Detecting Aflatoxin in Biogenic Dust Samples

Aflatoxin is a carcinogenic chemical that is sometimes produced when agricultural commodities are infested by the fungi Aspergillus flavus and A. Parasiticus. Aflatoxin has been found to be present in air samples taken around persons handling materials likely to be contaminated. The purpose of this investigation was to demonstrate the feasibility of using an Enzyme Linked Immunosorbent Assay (ELISA) test kit that was developed to screen for aflatoxin in bulk agricultural commodities, to an air sample. Samples were taken from two environments likely to be contaminated with aflatoxin, a dairy farm feed mixing operation and a peanut bagging operation. The dust collected from these environments was considered to be biogenic, in that it originated primarily from biological materials

Echo-Mapping of Swift J1753.5-0127

We present two epochs of coordinated X-ray-optical timing observations of the black hole candidate Swift J1753.5-0127 during its 2005 outburst. The first epoch in July occurred at outburst peak. Two consecutive nights of observations using the McDonald Observatory Argos camera with the Rossi X-ray Timing Explorer show a consistent correlation with an immediate response and an extended tail lasting ~5s. The properties of the variability and the correlation are consistent with thermal reprocessing in an accretion disk. The shortness of the lag suggests a short orbital period consistent with that recently claimed. The second epoch in August used the VLT FORS2 HIT mode again in conjunction with RXTE. Again a repeatable correlation is seen between two independent subsets of the data. In this case, though, the cross-correlation function has an unusual structure comprising a dip followed by a double-peak. We suggest that this may be equivalent to the dip plus single peak structure seen by Kanbach et al. (2001) in XTE J1118+480 and attributed there to synchrotron emission; a similar structure was seen during later activity of Swift J1753.5-0127 by Durant et al. (2008).Comment: 7 pages, accepted for publication in Monthly Notices of the Royal Astronomical Societ

Real-Space Observation of Quantum Tunneling by a Carbon Atom: Flipping Reaction of Formaldehyde on Cu(110)

We present a direct observation of carbon-atom tunneling in the flipping reaction of formaldehyde between its two mirror-reflected states on a Cu(110) surface using low-temperature scanning tunneling microscopy (STM). The flipping reaction was monitored in real time, and the reaction rate was found to be temperature independent below 10 K. This indicates that this reaction is governed by quantum mechanical tunneling, albeit involving a substantial motion of the carbon atom (∼1 Å). In addition, deuteration of the formaldehyde molecule resulted in a significant kinetic isotope effect (<i>R</i>_CH₂O/<i>R</i>_CD₂O ≈ 10). The adsorption structure, reaction pathway, and tunneling probability were examined by density functional theory calculations, which corroborate the experimental observations

Asynchronous food-web pathways could buffer the response of Serengeti predators to El Niño southern oscillation

Understanding how entire ecosystems maintain stability in the face of climatic and human disturbance is one of the most fundamental challenges in ecology. Theory suggests that a crucial factor determining the degree of ecosystem stability is simply the degree of synchrony with which different species in ecological food webs respond to environmental stochasticity. Ecosystems in which all food-web pathways are affected similarly by external disturbance should amplify variability in top carnivore abundance over time due to population interactions, whereas ecosystems in which a large fraction of pathways are nonresponsive or even inversely responsive to external disturbance will have more constant levels of abundance at upper trophic levels. To test the mechanism underlying this hypothesis, we used over half a century of demographic data for multiple species in the Serengeti (Tanzania) ecosystem to measure the degree of synchrony to variation imposed by an external environmental driver, the El Niño Southern Oscillation (ENSO). ENSO effects were mediated largely via changes in dry-season vs. wet-season rainfall and consequent changes in vegetation availability, propagating via bottom-up effects to higher levels of the Serengeti food web to influence herbivores, predators and parasites. Some species in the Serengeti food web responded to the influence of ENSO in opposite ways, whereas other species were insensitive to variation in ENSO. Although far from conclusive, our results suggest that a diffuse mixture of herbivore responses could help buffer top carnivores, such as Serengeti lions, from variability in climate. Future global climate changes that favor some pathways over others, however, could alter the effectiveness of such processes in the future