A Web-based archive of systematic review data

Systematic reviews have become increasingly critical to informing healthcare policy; however, they remain a time-consuming and labor-intensive activity. The extraction of data from constituent studies comprises a significant portion of this effort, an activity which is often needlessly duplicated, such as when attempting to update a previously conducted review or in reviews of overlapping topics

α-Syntrophin regulates ARMS localization at the neuromuscular junction and enhances EphA4 signaling in an ARMS-dependent manner

EphA4 signaling has recently been implicated in the regulation of synapse formation and plasticity. In this study, we show that ankyrin repeat-rich membrane spanning (ARMS; also known as a kinase D–interacting substrate of 220 kD), a substrate for ephrin and neurotrophin receptors, was expressed in developing muscle and was concentrated at the neuromuscular junction (NMJ). Using yeast two-hybrid screening, we identified a PDZ (PSD-95, Dlg, ZO-1) domain protein, α-syntrophin, as an ARMS-interacting protein in muscle. Overexpression of α-syntrophin induced ARMS clustering in a PDZ domain–dependent manner. Coexpression of ARMS enhanced EphA4 signaling, which was further augmented by the presence of α-syntrophin. Moreover, the ephrin-A1–induced tyrosine phosphorylation of EphA4 was reduced in C2C12 myotubes after the blockade of ARMS and α-syntrophin expression by RNA interference. Finally, α-syntrophin–null mice exhibited a disrupted localization of ARMS and EphA4 at the NMJ and a reduced expression of ARMS in muscle. Altogether, our findings suggest that ARMS may play an important role in regulating postsynaptic signal transduction through the syntrophin-mediated localization of receptor tyrosine kinases such as EphA4

Survival response to increased ceramide involves metabolic adaptation through novel regulators of glycolysis and lipolysis

The sphingolipid ceramide elicits several stress responses, however, organisms survive despite increased ceramide but how they do so is poorly understood. We demonstrate here that the AKT/FOXO pathway regulates survival in increased ceramide environment by metabolic adaptation involving changes in glycolysis and lipolysis through novel downstream targets. We show that ceramide kinase mutants accumulate ceramide and this leads to reduction in energy levels due to compromised oxidative phosphorylation. Mutants show increased activation of Akt and a consequent decrease in FOXO levels. These changes lead to enhanced glycolysis by upregulating the activity of phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase to provide energy. A second major consequence of AKT/FOXO reprogramming in the mutants is the increased mobilization of lipid from the gut through novel lipase targets, CG8093 and CG6277 for energy contribution. Ubiquitous reduction of these targets by knockdown experiments results in semi or total lethality of the mutants, demonstrating the importance of activating them. The efficiency of these adaptive mechanisms decreases with age and leads to reduction in adult life span of the mutants. In particular, mutants develop cardiac dysfunction with age, likely reflecting the high energy requirement of a well-functioning heart. The lipases also regulate physiological triacylglycerol homeostasis and are important for energy metabolism since midgut specific reduction of them in wild type flies results in increased sensitivity to starvation and accumulation of triglycerides leading to cardiac defects. The central findings of increased AKT activation, decreased FOXO level and activation of phosphoglyceromutase and pyruvate kinase are also observed in mice heterozygous for ceramide transfer protein suggesting a conserved role of this pathway in mammals. These data reveal novel glycolytic and non-autonomous lipolytic pathways in response to increased ceramide for sustenance of high energy demanding organ functions like the heart

Deglacial sea surface temperatures of the western tropical Pacific : a new look at old coral

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 19 (2004): PA4031, doi:10.1029/2004PA001084.Using Secondary Ion Mass Spectrometry (SIMS) ion microprobe techniques, we generated annual Sr/Ca cycles with subweekly resolution from chunks of Porites coral retrieved from a Tahiti barrier reef drill core (149°W, 17°S), representing the period 13,650 to 13,100 years B.P. The centers of pristine skeletal septa were selectively targeted with a 10 μm diameter ion beam spot, avoiding adjacent pore spaces occupied by secondary aragonite needles. Applying a Sr/Ca–sea surface temperature (SST) calibration equation derived from modern Tahiti Porites having the same low growth rate as the fossil specimens, we obtained SSTs ∼0.5°–1.5°C cooler during the Bølling-Allerod relative to the present day, with no significant change in seasonality. On the contrary, we estimate that analysis of bulk samples would yield excessively cool Sr/Ca-based SST estimates due to the occupation by secondary aragonite crystals of up to 50% of the skeletal pore space in the ancient samples. We find that growth rate effects on coral Sr/Ca further depress the apparent mean annual derived SSTs (by >3°C) and amplify the apparent seasonality by selectively enhancing wintertime cooling. Our microscale analysis of pristine skeleton and application of an appropriate growth-dependent calibration yield Sr/Ca-derived SSTs that are in good agreement with those derived from Mg/Ca ratios of calcitic foraminifera which indicate a continuous postglacial warming of the western tropical Pacific, in phase with the warming of the tropical Atlantic.Funds for this study were provided by NSF MG&G award number OCE-0241075

Models of Star-Planet Magnetic Interaction

Magnetic interactions between a planet and its environment are known to lead to phenomena such as aurorae and shocks in the solar system. The large number of close-in exoplanets that were discovered triggered a renewed interest in magnetic interactions in star-planet systems. Multiple other magnetic effects were then unveiled, such as planet inflation or heating, planet migration, planetary material escape, and even modification of the host star properties. We review here the recent efforts in modelling and understanding magnetic interactions between stars and planets in the context of compact systems. We first provide simple estimates of the effects of magnetic interactions and then detail analytical and numerical models for different representative scenarii. We finally lay out a series of future developments that are needed today to better understand and constrain these fascinating interactions.Comment: 23 pages, 10 figures, accepted as a chapter in the Handbook of Exoplanet

On products of long cycles: short cycle dependence and separation probabilities

We present various results on multiplying cycles in the symmetric group. One result is a generalisation of the following theorem of Boccara (1980): the number of ways of writing an odd permutation in the symmetric group on n symbols as a product of an n-cycle and an (n - 1)-cycle is independent of the permutation chosen. We give a number of different approaches of our generalisation. One partial proof uses an inductive method which we also apply to other problems. In particular, we give a formula for the distribution of the number of cycles over all products of cycles of fixed lengths. Another application is related to the recent notion of separation probabilities for permutations introduced by Bernardi, Du, Morales and Stanley (2014)

Cleavage of a model DNA replication fork by a Type I restriction endonuclease

Cleavage of a DNA replication fork leads to fork restoration by recombination repair. In prokaryote cells carrying restriction–modification systems, fork passage reduces genome methylation by the modification enzyme and exposes the chromosome to attack by the restriction enzyme. Various observations have suggested a relationship between the fork and Type I restriction enzymes, which cleave DNA at a distance from a recognition sequence. Here, we demonstrate that a Type I restriction enzyme preparation cleaves a model replication fork at its branch. The enzyme probably tracks along the DNA from an unmethylated recognition site on the daughter DNA and cuts the fork upon encountering the branch point. Our finding suggests that these restriction–modification systems contribute to genome maintenance through cell death and indicates that DNA replication fork cleavage represents a critical point in genome maintenance to choose between the restoration pathway and the destruction pathway