Activation of pluripotency genes in human fibroblast cells by a novel mRNA based approach

Background: Several methods have been used to induce somatic cells to re-enter the pluripotent state. Viral transduction of reprogramming genes yields higher efficiency but involves random insertions of viral sequences into the human genome. Although induced pluripotent stem (iPS) cells can be obtained with the removable PiggyBac transposon system or an episomal system, both approaches still use DNA constructs so that resulting cell lines need to be thoroughly analyzed to confirm they are free of harmful genetic modification. Thus a method to change cell fate without using DNA will be very useful in regenerative medicine. Methodology/Principal Findings: In this study, we synthesized mRNAs encoding OCT4, SOX2, cMYC, KLF4 and SV40 large T (LT) and electroporated them into human fibroblast cells. Upon transfection, fibroblasts expressed these factors at levels comparable to, or higher than those in human embryonic stem (ES) cells. Ectopically expressed OCT4 localized to the cell nucleus within 4 hours after mRNA introduction. Transfecting fibroblasts with a mixture of mRNAs encoding all five factors significantly increased the expression of endogenous OCT4, NANOG, DNMT3 beta, REX1 and SALL4. When such transfected fibroblasts were also exposed to several small molecules (valproic acid, BIX01294 and 5'-aza-2'-deoxycytidine) and cultured in human embryonic stem cell (ES) medium they formed small aggregates positive for alkaline phosphatase activity and OCT4 protein within 30 days. Conclusion/Significance: Our results demonstrate that mRNA transfection can be a useful approach to precisely control the protein expression level and short-term expression of reprogramming factors is sufficient to activate pluripotency genes in differentiated cells

Condensing Momentum Modes in 2-d 0A String Theory with Flux

We use a combination of conformal perturbation theory techniques and matrix model results to study the effects of perturbing by momentum modes two dimensional type 0A strings with non-vanishing Ramond-Ramond (RR) flux. In the limit of large RR flux (equivalently, mu=0) we find an explicit analytic form of the genus zero partition function in terms of the RR flux $q$ and the momentum modes coupling constant alpha. The analyticity of the partition function enables us to go beyond the perturbative regime and, for alpha>> q, obtain the partition function in a background corresponding to the momentum modes condensation. For momenta such that 0<p<2 we find no obstruction to condensing the momentum modes in the phase diagram of the partition function.Comment: 22 page

Multiscale studies of the three-dimensional dayside X-line

AbstractWe review recent experience from the Cluster, Double Star, and THEMIS missions for lessons that apply to the upcoming Magnetospheric Multiscale Mission (MMS) being developed for launch in 2014. On global scales, simulation and statistical studies lead to mean configurations of dayside reconnection, implying specific relative alignments of the inflow magnetic fields and X-line, with implications for MMS operations designed to maximize the number of close encounters with the diffusion region. At intermediate MHD-to-ion scales, reconstruction of features created by one or two X-lines have developed to the point where data from a cluster of spacecraft can determine their temporal trends and the approximate three-dimensional X-line structure. Recent petascale particle-in-cell (PIC) simulations of reconnection encompass three spatial dimensions with excellent resolution, and make striking predictions of electron scale physics that creates complex interacting flux ropes under component reconnection. High time resolution measurements from MMS will determine the detailed electron scale kinetics embedded within the global and MHD–ion scale contexts. These developments will lead to the refinement of our three-dimensional multiscale picture of reconnection, yielding improved understanding of the global, MHD, and local physics controlling the onset or quenching, variability, and mean rate of reconnection. This in turn will enable improved predictability of the structural features created by transient reconnection, and their space weather consequences

Elite male Flat jockeys display lower bone density and lower resting metabolic rate than their female counterparts: implications for athlete welfare

To test the hypothesis that daily weight-making is more problematic to health in male compared with female jockeys, we compared the bone-density and resting metabolic rate (RMR) in weight-matched male and female Flat-jockeys. RMR (kcal.kg-1 lean mass) was lower in males compared with females as well as lower bone-density Z-scores at the hip and lumbar spine. Data suggest the lifestyle of male jockeys’ compromise health more severely than females, possibly due to making-weight more frequently

Curved Flats, Pluriharmonic Maps and Constant Curvature Immersions into Pseudo-Riemannian Space Forms

We study two aspects of the loop group formulation for isometric immersions with flat normal bundle of space forms. The first aspect is to examine the loop group maps along different ranges of the loop parameter. This leads to various equivalences between global isometric immersion problems among different space forms and pseudo-Riemannian space forms. As a corollary, we obtain a non-immersibility theorem for spheres into certain pseudo-Riemannian spheres and hyperbolic spaces. The second aspect pursued is to clarify the relationship between the loop group formulation of isometric immersions of space forms and that of pluriharmonic maps into symmetric spaces. We show that the objects in the first class are, in the real analytic case, extended pluriharmonic maps into certain symmetric spaces which satisfy an extra reality condition along a totally real submanifold. We show how to construct such pluriharmonic maps for general symmetric spaces from curved flats, using a generalised DPW method.Comment: 21 Pages, reference adde

On The Problem of Particle Production in c=1 Matrix Model

We reconsider and analyze in detail the problem of particle production in the time dependent background of $c=1$ matrix model where the Fermi sea drains away at late time. In addition to the moving mirror method, which has already been discussed in hep-th/0403169 and hep-th/0403275, we describe yet another method of computing the Bogolubov coefficients which gives the same result. We emphasize that these Bogolubov coefficients are approximately correct for small value of the deformation parameter. We also study the time evolution of the collective field theory stress-tensor with a special point-splitting regularization. Our computations go beyond the approximation of the previous treatments and are valid at large coordinate distances from the boundary at a finite time and up-to a finite coordinate distance from the boundary at late time. In this region of validity our regularization produces a certain singular term that is precisely canceled by the collective field theory counter term in the present background. The energy and momentum densities fall off exponentially at large distance from the boundary to the values corresponding to the static background. This clearly shows that the radiated energy reaches the asymptotic region signaling the space-time decay.Comment: 37 pages, 5 figures. Section 6 is modified to clarify main accomplishments of the paper including a discussion comparing stress-tensor analysis with those preexisted in literature. Other modifications include minor changes in the text and addition of one reference. Version accepted for publication in JHE

Phytosterol and phytostanol-mediated epigenetic changes in cancer and other non-communicable diseases: a systematic review

Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of phytosterols/phytostanols reduces levels of circulating LDL-cholesterol, a causative biomarker of CVD, and is linked to a reduced risk of some cancers. Individuals who consume phytosterols/phytostanols in their diet may do so for many years as part of a non-pharmacological route to lower cholesterol or as part of a healthy diet. However, the impact of long term or high intakes of dietary phytosterols/phytostanols has not been on whole-body epigenetic changes before. The aim of this systematic review was to identify all publications that have evaluated changes to epigenetic mechanisms (post-translation modification of histones, DNA methylation and miRNA expression) in response to phytosterols/phytostanols. A systematic search was performed that returned 226 records, of which eleven were eligible for full-text analysis. Multiple phytosterols were found to inhibit expression of histone deacetylase (HDAC) enzymes and were also predicted to directly bind and impair HDAC activity. Phytosterols were found to inhibit the expression and activity of DNA methyl transferase enzyme 1 and reverse cancer-associated gene silencing. Finally, phytosterols have been shown to regulate over 200 miRNA, although only five of these were reported in multiple publications. Five tissue types (breast, prostate, macrophage, aortic epithelia and lung) were represented across the studies, and although phytosterols/phytostanols alter the molecular mechanisms of epigenetic inheritance in these mammalian cells, studies exploring meiotic or transgenerational inheritance were not found

Role of context in episodic memory: Evidence of selective facilitation in congruent environmental contexts in humans

The contribution of contextual factors on learning and memory has been well established, and it has been repeately shown that returning a participant to the context in which information was learned results in a facilitation for the recall of that information, while changing context can impair recall

Contain or eradicate? Optimizing the management goal for Australian acacia invasions in the face of uncertainty

Aim To identify whether eradication or containment is expected to be the most cost-effective management goal for an isolated invasive population when knowledge about the current extent is uncertain. Location Global and South Africa. Methods We developed a decision analysis framework to analyse the best management goal for an invasive species population (eradication, containment or take no action) when knowledge about the current extent is uncertain. We used value of information analysis to identify when investment in learning about the extent will improve this decision-making and tested the sensitivity of the conclusions to different parameters (e.g. spread rate, maximum extent, and management efficacy and cost). The model was applied to Acacia paradoxa DC, an Australian shrub with an estimated invasive extent of 310 ha on Table Mountain, South Africa. Results Under the parameters used, attempting eradication is cost-effective for infestations of up to 777 ha. However, if the invasion extent is poorly known, then attempting eradication is only cost-effective for infestations estimated as 296 ha or smaller. The value of learning is greatest (maximum of 8% saving) when infestation extent is poorly known and if it is close to the maximum extent for which attempting eradication is optimal. The optimal management action is most sensitive to the probability that the action succeeds (which depends on the extent), with the discount rate and cost of management also important, but spread rate less so. Over a 20-year time-horizon, attempting to eradicate A. paradoxa from South Africa is predicted to cost on average ZAR 8 million if the extent is known, and if our current estimate is poor, ZAR 33.6 million as opposed to ZAR 32.8 million for attempting containment. Main conclusions Our framework evaluates the cost-effectiveness of attempting eradication or containment of an invasive population that takes uncertainty in population extent into account. We show that incorporating uncertainty in the analysis avoids overly optimistic beliefs about the effectiveness of management enabling better management decisions. For A. paradoxa in South Africa, attempting to eradicate is likely to be cost-effective, particularly if resources are allocated to better understand and improve management efficacy.Centre of Excellence for Invasion Biolog