Hypoxia and Hypoglycemia synergistically regulate mRNA stability

Ischemic events, common in many diseases, result from decreased blood flow and impaired delivery of oxygen and glucose to tissues of the body. While much is known about the cellular transcriptional response to ischemia, much less is known about the posttranscriptional response to oxygen and glucose deprivation. The goal of this project was to investigate one such posttranscriptional response, the regulation of mRNA stability. To that end, we have identified several novel ischemia-related mRNAs that are synergistically stabilized by oxygen and glucose deprivation including VEGF, MYC, MDM2, and CYR61. This increase in mRNA half-life requires the synergistic effects of both low oxygen (1%) as well as low glucose ( 1 g/L) conditions. Oxygen or glucose deprivation alone fails to initiate the response, as exposure to either high glucose (4 g/L) or normoxic conditions inhibits the response. Furthermore, in response to hypoxia/hypoglycemia, the identified mRNAs are released from the RNA binding protein KHSRP which likely contributes to their stabilization

Incorporation of Radio Frequency Identification Tag in Dentures to Facilitate Recognition and Forensic Human Identification

Forensic identification using odontology is based on the comparison of ante-mortem and post mortem dental records. The insertion of a radio frequency identification (RFId) tag into dentures could be used as an aid to identify decomposed bodies, by storing personal identification data in a small transponder that can be radio-transmitted to a reader connected to a computer. A small passive, 12 x 2,1 mm, read-only RFId-tag was incorporated into the manufacture of three trial complete upper dentures and tested for a signal. The aim of this article is to demonstrate the feasibility of manufacturing such a dental prosthesis, the technical protocols for its implantation in the denture resin and its working principles. Future research and tests are required in order to verify human compatibility of the tagged denture and also to evaluate any potential deterioration in strength when subjected to high temperatures, or for damage resulting from everyday wear and tear. It should also be able to withstand the extreme conditions resulting from major accidents or mass disasters and procedures used to perform a forensic identification

Measuring our universe from galaxy redshift surveys

Galaxy redshift surveys have achieved significant progress over the last couple of decades. Those surveys tell us in the most straightforward way what our local universe looks like. While the galaxy distribution traces the bright side of the universe, detailed quantitative analyses of the data have even revealed the dark side of the universe dominated by non-baryonic dark matter as well as more mysterious dark energy (or Einstein's cosmological constant). We describe several methodologies of using galaxy redshift surveys as cosmological probes, and then summarize the recent results from the existing surveys. Finally we present our views on the future of redshift surveys in the era of Precision Cosmology.Comment: 82 pages, 31 figures, invited review article published in Living Reviews in Relativity, http://www.livingreviews.org/lrr-2004-

Large Scale Structure of the Universe

Galaxies are not uniformly distributed in space. On large scales the Universe displays coherent structure, with galaxies residing in groups and clusters on scales of ~1-3 Mpc/h, which lie at the intersections of long filaments of galaxies that are >10 Mpc/h in length. Vast regions of relatively empty space, known as voids, contain very few galaxies and span the volume in between these structures. This observed large scale structure depends both on cosmological parameters and on the formation and evolution of galaxies. Using the two-point correlation function, one can trace the dependence of large scale structure on galaxy properties such as luminosity, color, stellar mass, and track its evolution with redshift. Comparison of the observed galaxy clustering signatures with dark matter simulations allows one to model and understand the clustering of galaxies and their formation and evolution within their parent dark matter halos. Clustering measurements can determine the parent dark matter halo mass of a given galaxy population, connect observed galaxy populations at different epochs, and constrain cosmological parameters and galaxy evolution models. This chapter describes the methods used to measure the two-point correlation function in both redshift and real space, presents the current results of how the clustering amplitude depends on various galaxy properties, and discusses quantitative measurements of the structures of voids and filaments. The interpretation of these results with current theoretical models is also presented.Comment: Invited contribution to be published in Vol. 8 of book "Planets, Stars, and Stellar Systems", Springer, series editor T. D. Oswalt, volume editor W. C. Keel, v2 includes additional references, updated to match published versio

Host Cell Egress and Invasion Induce Marked Relocations of Glycolytic Enzymes in Toxoplasma gondii Tachyzoites

Apicomplexan parasites are dependent on an F-actin and myosin-based motility system for their invasion into and escape from animal host cells, as well as for their general motility. In Toxoplasma gondii and Plasmodium species, the actin filaments and myosin motor required for this process are located in a narrow space between the parasite plasma membrane and the underlying inner membrane complex, a set of flattened cisternae that covers most the cytoplasmic face of the plasma membrane. Here we show that the energy required for Toxoplasma motility is derived mostly, if not entirely, from glycolysis and lactic acid production. We also demonstrate that the glycolytic enzymes of Toxoplasma tachyzoites undergo a striking relocation from the parasites' cytoplasm to their pellicles upon Toxoplasma egress from host cells. Specifically, it appears that the glycolytic enzymes are translocated to the cytoplasmic face of the inner membrane complex as well as to the space between the plasma membrane and inner membrane complex. The glycolytic enzymes remain pellicle-associated during extended incubations of parasites in the extracellular milieu and do not revert to a cytoplasmic location until well after parasites have completed invasion of new host cells. Translocation of glycolytic enzymes to and from the Toxoplasma pellicle appears to occur in response to changes in extracellular [K+] experienced during egress and invasion, a signal that requires changes of [Ca2+]c in the parasite during egress. Enzyme translocation is, however, not dependent on either F-actin or intact microtubules. Our observations indicate that Toxoplasma gondii is capable of relocating its main source of energy between its cytoplasm and pellicle in response to exit from or entry into host cells. We propose that this ability allows Toxoplasma to optimize ATP delivery to those cellular processes that are most critical for survival outside host cells and those required for growth and replication of intracellular parasites

Medication administration errors for older people in long-term residential care

Background Older people in long-term residential care are at increased risk of medication errors. The purpose of this study was to evaluate a computerised barcode medication management system designed to improve drug administrations in residential and nursing homes, including comparison of error rates and staff awareness in both settings. Methods All medication administrations were recorded prospectively for 345 older residents in thirteen care homes during a 3-month period using the computerised system. Staff were surveyed to identify their awareness of administration errors prior to system introduction. Overall, 188,249 attempts to administer medication were analysed to determine the prevalence of potential medication administration errors (MAEs). Error classifications included attempts to administer medication at the wrong time, to the wrong person or discontinued medication. Analysis compared data at residential and nursing home level and care and nursing staff groups. Results Typically each resident was exposed to 206 medication administration episodes every month and received nine different drugs. Administration episodes were more numerous (p < 0.01) in nursing homes (226.7 per resident) than in residential homes (198.7). Prior to technology introduction, only 12% of staff administering drugs reported they were aware of administration errors being averted in their care home. Following technology introduction, 2,289 potential MAEs were recorded over three months. The most common MAE was attempting to give medication at the wrong time. On average each resident was exposed to 6.6 potential errors. In total, 90% of residents were exposed to at least one MAE with over half (52%) exposed to serious errors such as attempts to give medication to the wrong resident. MAEs rates were significantly lower (p < 0.01) in residential homes than nursing homes. The level of non-compliance with system alerts was low in both settings (0.075% of administrations) demonstrating virtually complete error avoidance. Conclusion Potentially inappropriate administration of medication is a serious problem in long-term residential care. A computerised barcode system can accurately and automatically detect inappropriate attempts to administer drugs to residents. This tool can reliably be used by care staff as well as nurses to improve quality of care and patient safety

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

Primary care physicians' use of family history for cancer risk assessment

<p>Abstract</p> <p>Background</p> <p>Family history (FH) assessment is useful in identifying and managing patients at increased risk for cancer. This study assessed reported FH quality and associations with physician perceptions.</p> <p>Methods</p> <p>Primary care physicians practicing in two northeastern U.S. states were surveyed (n = 880; 70% response rate). Outcome measures of FH quality were extent of FH taken and ascertaining age at cancer diagnosis for affected family members. Predictors of quality measured in this survey included: perceived advantages and disadvantages of collecting FH information, knowledge of management options, access to supportive resources, and confidence in ability to interpret FH.</p> <p>Results</p> <p>Reported collection of information regarding second degree blood relatives and age of diagnosis among affected relatives was low. All hypothesized predictors were associated with measures of FH quality, but not all were consistent independent predictors. Perceived advantages of taking a family history, access to supportive resources, and confidence in ability to identify and manage higher risk patients were independent predictors of both FH quality measures. Perceived disadvantages of taking a family history was independently associated one measure of FH quality. Knowledge of management options was not independently associated with either quality measure.</p> <p>Conclusions</p> <p>Modifiable perception and resource factors were independently associated with quality of FH taking in a large and diverse sample of primary care physicians. Improving FH quality for identification of high risk individuals will require multi-faceted interventions.</p

The Typical Flight Performance of Blowflies: Measuring the Normal Performance Envelope of Calliphora vicina Using a Novel Corner-Cube Arena

Despite a wealth of evidence demonstrating extraordinary maximal performance, little is known about the routine flight performance of insects. We present a set of techniques for benchmarking performance characteristics of insects in free flight, demonstrated using a model species, and comment on the significance of the performance observed. Free-flying blowflies (Calliphora vicina) were filmed inside a novel mirrored arena comprising a large (1.6 m1.6 m1.6 m) corner-cube reflector using a single high-speed digital video camera (250 or 500 fps). This arrangement permitted accurate reconstruction of the flies' 3-dimensional trajectories without the need for synchronisation hardware, by virtue of the multiple reflections of a subject within the arena. Image sequences were analysed using custom-written automated tracking software, and processed using a self-calibrating bundle adjustment procedure to determine the subject's instantaneous 3-dimensional position. We illustrate our method by using these trajectory data to benchmark the routine flight performance envelope of our flies. Flight speeds were most commonly observed between 1.2 ms−1 and 2.3 ms−1, with a maximum of 2.5 ms−1. Our flies tended to dive faster than they climbed, with a maximum descent rate (−2.4 ms−1) almost double the maximum climb rate (1.2 ms−1). Modal turn rate was around 240°s−1, with maximal rates in excess of 1700°s−1. We used the maximal flight performance we observed during normal flight to construct notional physical limits on the blowfly flight envelope, and used the distribution of observations within that notional envelope to postulate behavioural preferences or physiological and anatomical constraints. The flight trajectories we recorded were never steady: rather they were constantly accelerating or decelerating, with maximum tangential accelerations and maximum centripetal accelerations on the order of 3 g