True Reversal Research Articles

The Use of Descriptive Praise to Increase Diversity During Easel Painting

The purpose of this article was to describe 2 studies that examined the relation between descriptive praise and generalized diversity of forms and colors used during art activities in young children. Study I used a true reversal design to examine the relation between descriptive praise and diversity during art activities. All 4 children had small increases with descriptive praise, but there was considerable variability across children and conditions. In Study II, a multiple probe design was employed across 3 children to examine the relation between descriptive praise and diversity of forms and colors used in art activities. All 3 children used more diverse forms and colors with descriptive praise, although increases were small.

Genetic analysis of revertants isolated from the rod-fragile fliF mutant of Salmonella.

FliF is the protein comprising the MS-ring of the bacterial flagellar basal body, which is the base for the assembly of flagellar axial structures. From a fliF mutant that easily releases the rod-hook-filament in viscous environments, more than 400 revertants that recovered their swarming ability in viscous conditions, were isolated. The second-site mutations were determined for approximately 70% of them. There were three regions where the mutations were localized: two in Region I, 112 in Region II, and 71 in Region III including the true reversion. In Region I, second-site mutations were found in FlgC and FlgF of the proximal rod, suggesting that they affect the interaction between the MS-ring and the rod. In Region II, there were 69 and 42 mutations in MotA and MotB, respectively, suggesting that the second-site mutations in MotA and MotB may decrease the rotational speed of the flagellar motor to reduce the probability of releasing the rod under this condition. One exception is a mutation in FlhC that caused a down regulation of the flagellar proteins production but it may directly affect transcription or translation of motA and motB. In Region III, there were 44, 24, and 3 mutations in FliG, FliM, and FliF, respectively. There were no second-site mutations identified in FliN although it is involved in torque generation as a component of the C-ring. Many of the mutations were involved in the motor rotation, and it is suggested that such reduced speeds result in stabilizing the filament attachment to the motor.

Invited Commentary

Invited Commentary

Forma sociale della psicologia alfabetica. Il teatro nell'ipotesi "neuroculturale" di de Kerckhove

Following the studies of Marshall McLuhan and Eric Havelock, Derrick De Kerchkove argues that the invention of theater by the Athenian community between the sixth and fifth centuries BC marks a decisive moment in the formation of Western mind, to be closely connected with the contemporary invention of alphabetic writing. Since attending to the theatrical performance requires attention and behavior characterized by immobility, distance and mental reflection, theater would have contributed to the emergence of modes of perception and participation in social life dependent on the increasing value of eye and sight, while promoting the decline of the oral and tribal ear. Theater was indeed one of the main instruments of what de Kerckhove call “desensorialization” of knowledge and experience. Has the profound transformation of communication media brought to some change? Signals from experimental theater of the second half of the twentieth century seem to suggest a significant change in the status of the performing arts, if not a true reversal. In the context of contemporary communicaton, characterized by virtuality and digital networks, the practice of performing arts (theatre, music, dance) acquires a predominantly opposite value as a potential accelerator of “ri-sensorialization” of knowledge.

The impact of the reform of the Italian higher education system on the labour market for young graduates

This article assesses the effectiveness of a reform of the higher education system aimed at stimulating employability and faster access to the labour market for Italian graduates. Using the Taylor formula, the evolution of the employment rates has been followed through the movements and interaction of activity and unemployment rates. The progress in the level of educational attainments has not been accompanied by a true reversal of the weaknesses within the Italian youth labour market. Two main results emerge. First, delayed entry into the Italian labour market remains a peculiar characteristic of young graduates. Second, the comparison within the 25–29 age group reveals weaker results among first-level graduates. Policy interventions are suggested.

RAG1 Reversion Mosaicism in a Patient with Omenn Syndrome

To identify mechanisms of disease in a child born to consanguineous parents, who presented with Omenn syndrome (OS) and was found to carry a heterozygous RAG1 mutation in peripheral blood DNA. Mutation analysis was performed on whole blood and buccal swab DNA. Recombination activity of the mutant RAG1 protein and diversity of T cell repertoire were tested. Apparent heterozygosity for a novel, functionally null RAG1 mutation in peripheral blood DNA from a patient with OS was shown to be secondary to true somatic reversion. Analysis of T cell repertoire demonstrated expression of various TCRBV families, but an overall restricted pattern. This is the first case of true somatic reversion of a RAG1 mutation in a patient with OS. The reversion event likely occurred at a stage where only a limited pool of T cell progenitors capable of performing V(D)J recombination could be generated. This work emphasizes the importance of performing functional studies to investigate the significance of novel genetic variants, and to consider somatic reversion as a possible disease modifier in SCID.

Applications of the Dynamic Brillouin Gratings to Ultrawideband Communications

Unconventional signal processing, such as all-optical signal time differentiation and true time reversal, can be realized on sub-nanosecond pulses, by exploiting dynamic Brillouin gratings in optical fibers. The performance of such optical processors, to generate ultrawideband (including high-order) Gaussian pulses and to implement an ultrawideband time reversal mirror, is numerically assessed.

All-optical signal processing using dynamic Brillouin gratings

The manipulation of dynamic Brillouin gratings in optical fibers is demonstrated to be an extremely flexible technique to achieve, with a single experimental setup, several all-optical signal processing functions. In particular, all-optical time differentiation, time integration and true time reversal are theoretically predicted, and then numerically and experimentally demonstrated. The technique can be exploited to process both photonic and ultra-wide band microwave signals, so enabling many applications in photonics and in radio science.

Targeting the epigenome in lung cancer: expanding approaches to epigenetic therapy.

Epigenetic aberrations offer dynamic and reversible targets for cancer therapy; increasingly, alteration via overexpression, mutation, or rearrangement is found in genes that control the epigenome. Such alterations suggest a fundamental role in carcinogenesis. Here, we consider three epigenetic mechanisms: DNA methylation, histone tail modification and non-coding, microRNA regulation. Evidence for each of these in lung cancer origin or progression has been gathered, along with evidence that epigenetic alterations might be useful in early detection. DNA hypermethylation of tumor suppressor promoters has been observed, along with global hypomethylation and hypoacetylation, suggesting an important role for tumor suppressor gene silencing. These features have been linked as prognostic markers with poor outcome in lung cancer. Several lines of evidence have also suggested a role for miRNA in carcinogenesis and in outcome. Cigarette smoke downregulates miR-487b, which targets both RAS and MYC; RAS is also a target of miR-let-7, again downregulated in lung cancer. Together the evidence implicates epigenetic aberration in lung cancer and suggests that targeting these aberrations should be carefully explored. To date, DNA methyltransferase and histone deacetylase inhibitors have had minimal clinical activity. Explanations include the possibility that the agents are not sufficiently potent to invoke epigenetic reversion to a more normal state; that insufficient time elapses in most clinical trials to observe true epigenetic reversion; and that doses often used may provoke off-target effects such as DNA damage that prevent epigenetic reversion. Combinations of epigenetic therapies may address those problems. When epigenetic agents are used in combination with chemotherapy or targeted therapy it is hoped that downstream biological effects will provoke synergistic cytotoxicity. This review evaluates the challenges of exploiting the epigenome in the treatment of lung cancer.

Monthly Follow-ups of Interferon-γ Release Assays Among Health-care Workers in Contact With Patients With TB

Interferon-γ (IFN-γ) release assays (IGRAs), which can overcome several limitations of the tuberculin skin test in detecting latent TB infection, were introduced recently in routine clinical practice. However, IGRAs are highly dynamic tests, and the T-cell responses tend to fluctuate over time. We wanted to evaluate the conversion and reversion rates of monthly IGRAs over 1 year among health-care workers (HCWs) in contact with patients with TB in South Korea, a country with an intermediate TB burden. Forty-nine HCWs in contact with patients with active pulmonary TB were prospectively enrolled. Interviews on exposure to patients with active TB, a physical examination, and a QuantiFERON TB Gold In-Tube assay (QFT-GIT) were carried out monthly for 1 year. Among 48 participants, 25 (52%) showed inconsistent results in serial testing. When an increase from< 0.35 IU/mL to ≥ 0.70 IU/mL was applied as the definition of a conversion, inconsistent IGRA results were identified in 13 participants (27.0%). Consistency in QFT-GIT results was associated with age, length of service, and baseline IFN-γ levels, but not with the profession of the participant, degree of TB exposure, or wearing of an N95 mask. In five participants, fluctuations in IFN-γ levels showed levels > 0.70 IU/mL two or more times. Fluctuation in IGRA findings was common when HCWs in contact with patients with TB were tested monthly. This could be a result of poor reproducibility of the assay, repeated infection and true reversion, or periodic secretion of antigens from Mycobacterium tuberculosis. ClinicalTrials.gov; No.: NCT01121068; URL: www.clinicaltrials.gov

Evidence‐Based Medicine: What's the Evidence?

Evidence‐Based Medicine: What's the Evidence?

Umbria-Marche Basin, Central Italy: A Reference Section for the Aptian-Albian Interval at Low Latitudes

No abstract available. &lt;br&gt;&lt;br&gt; doi:&lt;a href="http://dx.doi.org/:10.2204/iodp.sd.13.07.2011" target="_blank"&gt;:10.2204/iodp.sd.13.07.2011&lt;/a&gt;

DO LARVAL TRAITS RE-EVOLVE? EVIDENCE FROM THE EMBRYOGENESIS OF A DIRECT-DEVELOPING SALAMANDER, PLETHODON CINEREUS

Recent molecular phylogenies suggest the surprising reacquisition of posthatching metamorphosis within an otherwise direct-developing clade of lungless salamanders (family Plethodontidae). Metamorphosis was long regarded as plesiomorphic for plethodontids, yet the genus Desmognathus, which primarily includes metamorphosing species, is now nested within a much larger clade of direct-developing species. The extent to which the putative reacquisition of metamorphosis in Desmognathus represents a true evolutionary reversal is contingent upon the extent to which both larva-specific features and metamorphosis were actually lost during the evolution of direct development. In this study we analyze development of the hyobranchial skeleton, which is dramatically remodeled during salamander metamorphosis, in the direct-developing red-backed salamander, Plethodon cinereus. We find dramatic remodeling of the hyobranchial skeleton during embryogenesis in P. cinereus and the transient appearance of larva-specific cartilages. Hyobranchial development in this direct-developing plethodontid is highly similar to that in metamorphosing plethodontids (e.g., Desmognathus). The proposed reacquisition of hyobranchial metamorphosis within Desmognathus does not represent the "re-evolution" of a lost phenotype, but instead the elaboration of an existing developmental sequence.

Pyrovanadolysis, a Pyrophosphorolysis-like Reaction Mediated by Pyrovanadate, Mn2+, and DNA Polymerase of Bacteriophage T7

DNA polymerases catalyze the 3'-5'-pyrophosphorolysis of a DNA primer annealed to a DNA template in the presence of pyrophosphate (PP(i)). In this reversal of the polymerization reaction, deoxynucleotides in DNA are converted to deoxynucleoside 5'-triphosphates. Based on the charge, size, and geometry of the oxygen connecting the two phosphorus atoms of PP(i), a variety of compounds was examined for their ability to carry out a reaction similar to pyrophosphorolysis. We describe a manganese-mediated pyrophosphorolysis-like activity using pyrovanadate (VV) catalyzed by the DNA polymerase of bacteriophage T7. We designate this reaction pyrovanadolysis. X-ray absorption spectroscopy reveals a shorter Mn-V distance of the polymerase-VV complex than the Mn-P distance of the polymerase-PP(i) complex. This structural arrangement at the active site accounts for the enzymatic activation by Mn-VV. We propose that the Mn(2+), larger than Mg(2+), fits the polymerase active site to mediate binding of VV into the active site of the polymerase. Our results may be the first documentation that vanadium can substitute for phosphorus in biological processes.

Functional Analysis of Two Cavities in Flavivirus NS5 Polymerase

Flavivirus NS5 protein encodes methyltransferase and RNA-dependent RNA polymerase (RdRp) activities. Structural analysis of flavivirus RdRp domains uncovered two conserved cavities (A and B). Both cavities are located in the thumb subdomains and represent potential targets for development of allosteric inhibitors. In this study, we used dengue virus as a model to analyze the function of the two RdRp cavities. Amino acids from both cavities were subjected to mutagenesis analysis in the context of genome-length RNA and recombinant NS5 protein; residues critical for viral replication were subjected to revertant analysis. For cavity A, we found that only one (Lys-756) of the seven selected amino acids is critical for viral replication. Alanine substitution of Lys-756 did not affect the RdRp activity, suggesting that this residue functions through a nonenzymatic mechanism. For cavity B, all four selected amino acids (Leu-328, Lys-330, Trp-859, and Ile-863) are critical for viral replication. Biochemical and revertant analyses showed that three of the four mutated residues (Leu-328, Trp-859, and Ile-863) function at the step of initiation of RNA synthesis, whereas the fourth residue (Lys-330) functions by interacting with the viral NS3 helicase domain. Collectively, our results have provided direct evidence for the hypothesis that cavity B, but not cavity A, from dengue virus NS5 polymerase could be a target for rational drug design.

Substrate Specificity and Catalysis by the Editing Active Site of Alanyl-tRNA Synthetase from Escherichia coli

Aminoacyl-tRNA synthetases (ARSs) enhance the fidelity of protein synthesis through multiple mechanisms, including hydrolysis of the adenylate and cleavage of misacylated tRNA. Alanyl-tRNA synthetase (AlaRS) limits misacylation with glycine and serine by use of a dedicated editing domain, and a mutation in this activity has been genetically linked to a mouse model of a progressive neurodegenerative disease. Using the free-standing Pyrococcus horikoshii AlaX editing domain complexed with serine as a model and both Ser-tRNA(Ala) and Ala-tRNA(Ala) as substrates, the deacylation activities of the wild type and five different Escherichia coli AlaRS editing site substitution mutants were characterized. The wild-type AlaRS editing domain deacylated Ser-tRNA(Ala) with a k(cat)/K(M) of 6.6 × 10(5) M(-1) s(-1), equivalent to a rate enhancement of 6000 over the rate of enzyme-independent deacylation but only 12.2-fold greater than the rate with Ala-tRNA(Ala). While the E664A and T567G substitutions only minimally decreased k(cat)/K(M,) Q584H, I667E, and C666A AlaRS were more compromised in activity, with decreases in k(cat)/K(M) in the range of 6-, 6.6-, and 15-fold. C666A AlaRS was 1.7-fold more active on Ala-tRNA(Ala) relative to Ser-tRNA(Ala), providing the only example of a true reversal of substrate specificity and highlighting a potential role of the coordinated zinc in editing substrate specificity. Along with the potentially serious physiological consequences of serine misincorporation, the relatively modest specificity of the AlaRS editing domain may provide a rationale for the widespread phylogenetic distribution of AlaX free-standing editing domains, thereby contributing a further mechanism to lower concentrations of misacylated tRNA(Ala).

Serial testing with an interferon-γ release assay in German healthcare workers.

Aim: Data concerning conversion and reversion rates in the serial testing of healthcare workers (HCWs) is rare. So far, there is no consensus on how to define and interpret interferon-gamma release assays (IGRA) conversions and reversions, or how to deal with such results. We analysed conversion and reversion rates in the serial testing of HCWs using an IGRA.Methods: The study population comprises 287 HCWs, who participated in routine occupational safety and health screening for latent tuberculosis infection (LTBI) with the QuantiFERON-TB® Gold In-Tube assay (QFT). Four different definitions for conversion and reversion were applied: 1) transgression or regression above/below the cut-off; 2) increase from <0.2 to >0.7 IU/ml or decrease from >0.7 to <0.2 IU/ml; 3) transgression or regression above/below the cut-off plus change of ≥0.50 IU/ml; and 4) transgression or regression above/below the cut-off plus change of ≥0.70 IU/ml.Results: The highest conversion and reversion rates of 6.1% (95% CI 3.5 to 9.9) and 32.6% (95% CI 19.1 to 48.5) respectively were observed with the least stringent definition of negative to positive. The most stringent definition of an increase of ≥0.7 IU/ml above the cut-point produced the lowest conversion rate of 2.5% (95% CI 0.9 to 5.3). Using an uncertainty zone from 0.2 to 0.7 IU/ml gave low conversion (2.6%) and reversion rates (15.4%). Conclusion: Our data confirmed the findings of previous studies that suggest that a simplistic dichotomous negative to positive definition of the IGRA might be deceptive because of the high number of spontaneous conversions and reversions. Therefore using an uncertainty zone around the cut-point (e.g. 0.2 to 0.7 IU/ml) could improve the discrimination between unspecific variation around the diagnostic cut-off and true conversion or reversion.

Is it really a true reversal?

Is it really a true reversal?

Ischemic diffusion lesion reversal is uncommon and rarely alters perfusion-diffusion mismatch

The use of diffusion-weighted imaging (DWI) to define irreversibly damaged infarct core is challenged by data suggesting potential partial reversal of DWI abnormalities. However, previous studies have not considered infarct involution. We investigated the prevalence of DWI lesion reversal in the EPITHET Trial. EPITHET randomized patients 3-6 hours from onset of acute ischemic stroke to tissue plasminogen activator (tPA) or placebo. Pretreatment DWI and day 90 T2-weighted images were coregistered. Apparent reversal of the acute ischemic lesion was defined as DWI lesion not incorporated into the final infarct. Voxels of CSF at follow-up were subtracted from regions of apparent DWI lesion reversal to adjust for infarct atrophy. All cases were visually cross-checked to exclude volume loss and coregistration inaccuracies. In 60 patients, apparent reversal involved a median 46% of the baseline DWI lesion (median volume 4.9 mL, interquartile range 2.6-9.5 mL) and was associated with less severe baseline hypoperfusion (p < 0.001). Apparent reversal was increased by reperfusion, regardless of the severity of baseline hypoperfusion (p = 0.02). However, the median volume of apparent reversal was reduced by 45% when CSF voxels were subtracted (2.7 mL, interquartile range 1.6-6.2 mL, p < 0.001). Perfusion-diffusion mismatch classification only rarely altered after adjusting the baseline DWI volume for apparent reversal. Visual comparison of acute DWI to subacute DWI or day 90 T2 identified minor regions of true DWI lesion reversal in only 6 of 93 patients. True DWI lesion reversal is uncommon in ischemic stroke patients. The volume of apparent lesion reversal is small and would rarely affect treatment decisions based on perfusion-diffusion mismatch.

Dynamic Price Competition with Network Effects

I consider a dynamic model of competition between two proprietary networks. Consumers die and are replaced with a constant hazard rate. Firms compete for new consumers to join their network by offering network entry prices (which may be below cost). New consumers have a privately known preference for each network. Upon joining a network, in each period consumers enjoy a benefit which is increasing in network size during that period. Firms receive revenues from new consumers as well as from consumers already belonging to their network. Using a combination of analytical and numerical methods, I discuss various properties of the equilibrium. I show that very small or very large networks tend to price higher than networks of intermediate size. I also show that, around symmetric states, the gap between the large and the small network tends to widen (increasing dominance) whereas the opposite is true (reversion to the mean) around very asymmetric states.