Inhibition of human telomerase by a G-quadruplex-interaction compound

Certain non-nucleoside compounds that will selectively inhibit telomerase by targeting the nucleic add structures, such as G-quadruplexes, that may be associated with human telomeres or telomerase have been identified. Inhibition of human telomerase by two perylenetetracarboxylic acid diimides and a carbocyanine has been demonstrated. 1H-NMR studies have evidenced the stabilization of a G-quadruplex by the perylenetetracarboxylic acid diimide compounds and provided evidence that these and structurally related compounds inhibit the telomerase enzyme by a mechanism consistent with interaction with G-quadruplex structures.Board of Regents, University of Texas Syste

Regional manifestation of the widespread disruption of soil-landscapes by the 4kyr BP impact-linked dust event using pedo-sedimentary micro-fabrics

The co-occurrence of a sharp dust peak, low lake levels, forest reduction, and ice retreat at ca. 4-kyr BP throughout tropical Africa and West Asia have been widely explained as the effect of an abrupt climate change. The detailed study of soils and archaeological records provided evidence to re-interpret the 4 kyr BP dust event linked rather to the fallback of an impact-ejecta, but not climate change. Here we aim to further investigate the exceptional perturbation of the soil-landscapes widely initiated by the 4 kyr BP dust event. Results are based on soil data from the eastern Khabur basin (North-East Syria), the Vera Basin (Spain), and the lower Moche Valley (West Peru) compared with a new study at the reference site of Ebeon (West France). The quality of the 4 kyr BP dust signal and the related environmental records are investigated through a micromorphological study of pedo-sedimentary micro-fabrics combined with SEM-microprobe, mineralogical, and geochemical analyses.In the four regions studied, the intact 4 kyr BP signal is identifi ed as a discontinuous burnt soil surface with an exotic dust assemblage assigned to the distal fallout of an impact-ejecta. Its unusual two-fold micro-facies is interpreted as (1) flash heating due to pulverization of the hot ejecta cloud at the soil surface, and (2) high energy deflation caused by the impact-related air blast. Disruption of the soil surface is shown to have been rapidly followed by a major de-stabilisation of the soil cover. Local factors and regional settings have exerted a major control on the timing, duration, and magnitude of landscape disturbances. Studies showed how a high quality signal allows to discriminate the short-term severe landscape disturbances linked to the exceptional 4 kyr BP dust event from more gradual environmental changes triggered by climate shift at the same time

The pharmacologic treatment of problematic sexual interests, paraphilic disorders and sexual preoccupation in adult men who have committed a sexual offence

This paper provides an international perspective on the use of medications to treat problematic sexual interests, paraphilic disorders and sexual preoccupation in men who have committed a sexual offence. Experts from Canada, Czech Republic (CR), Russia, United Kingdom (UK), and the United States of America (US) met in Prague, CR in May 2017 to review and compare their treatment approaches. This report is a summary of their discussions, including empirical data from CR and Russia which have not previously been published in the English language. All participants agreed that continuing international collaboration would be very useful for the development of ethical international prescribing guidelines, as well as pooling data from studies on the efficacy and utility of pharmacological and other biological treatments for people who have committed sexual offences

The influence of implicit theories and offender characteristics on judgements of sexual offenders: a moderated mediation analysis

The psychological factors underpinning responses to sexual offenders are beginning to receive increased empirical scrutiny. One such factor is offender representativeness, which refers to the extent to which a given offender example matches a stereotype of those who are typically labelled as 'sexual offenders'. Using a sample of 252 community members, we examined the role of implicit theories about sexual offenders (i.e., whether sexual offending is seen as fixed or malleable) in mediating the relationship between affective responses to sexual offenders and policy outcome judgements. We found support for this mediating effect, although this was eliminated when participants were presented with a 'non-representative' offender vignette. We argue that the relationship between affective responses and policy judgements is contingent on the activation of a sexual offender stereotype, and that this link can be disrupted via the increased presentation of non-stereotypical case examples. Implications for public debate and professional practice are discussed

A comparative study of Tam3 and Ac transposition in transgenic tobacco and petunia plants

Transposition of the Anthirrinum majus Tam3 element and the Zea mays Ac element has been monitored in petunia and tobacco plants. Plant vectors were constructed with the transposable elements cloned into the leader sequence of a marker gene. Agrobacterium tumefaciens-mediated leaf disc transformation was used to introduce the transposable element constructs into plant cells. In transgenic plants, excision of the transposable element restores gene expression and results in a clearly distinguishable phenotype. Based on restored expression of the hygromycin phosphotransferase II (HPTII) gene, we established that Tam3 excises in 30% of the transformed petunia plants and in 60% of the transformed tobacco plants. Ac excises from the HPTII gene with comparable frequencies (30%) in both plant species. When the β-glucuronidase (GUS) gene was used to detect transposition of Tam3, a significantly lower excision frequency (13%) was found in both plant species. It could be shown that deletion of parts of the transposable elements Tam3 and Ac, removing either one of the terminal inverted repeats (TIR) or part of the presumptive transposase coding region, abolished the excision from the marker genes. This demonstrates that excision of the transposable element Tam3 in heterologous plant species, as documented for the autonomous element Ac, also depends on both properties. Southern blot hybridization shows the expected excision pattern and the reintegration of Tam3 and Ac elements into the genome of tobacco plants.

Radically Rethinking Agriculture for the 21st Century

Population growth, arable land and fresh water limits, and climate change have profound implications for the ability of agriculture to meet this century’s demands for food, feed, fiber, and fuel while reducing the environmental impact of their production. Success depends on the acceptance and use of contemporary molecular techniques, as well as the increasing development of farming systems that use saline water and integrate nutrient flows

Safe uses of Hill's model: an exact comparison with the Adair-Klotz model

<p>Abstract</p> <p>Background</p> <p>The Hill function and the related Hill model are used frequently to study processes in the living cell. There are very few studies investigating the situations in which the model can be safely used. For example, it has been shown, at the mean field level, that the dose response curve obtained from a Hill model agrees well with the dose response curves obtained from a more complicated Adair-Klotz model, provided that the parameters of the Adair-Klotz model describe strongly cooperative binding. However, it has not been established whether such findings can be extended to other properties and non-mean field (stochastic) versions of the same, or other, models.</p> <p>Results</p> <p>In this work a rather generic quantitative framework for approaching such a problem is suggested. The main idea is to focus on comparing the particle number distribution functions for Hill's and Adair-Klotz's models instead of investigating a particular property (e.g. the dose response curve). The approach is valid for any model that can be mathematically related to the Hill model. The Adair-Klotz model is used to illustrate the technique. One main and two auxiliary similarity measures were introduced to compare the distributions in a quantitative way. Both time dependent and the equilibrium properties of the similarity measures were studied.</p> <p>Conclusions</p> <p>A strongly cooperative Adair-Klotz model can be replaced by a suitable Hill model in such a way that any property computed from the two models, even the one describing stochastic features, is approximately the same. The quantitative analysis showed that boundaries of the regions in the parameter space where the models behave in the same way exhibit a rather rich structure.</p

Genomic repeat abundances contain phylogenetic signal

A large proportion of genomic information, particularly repetitive elements, is usually ignored when researchers are using next-generation sequencing. Here we demonstrate the usefulness of this repetitive fraction in phylogenetic analyses, utilizing comparative graph-based clustering of next-generation sequence reads, which results in abundance estimates of different classes of genomic repeats. Phylogenetic trees are then inferred based on the genome-wide abundance of different repeat types treated as continuously varying characters; such repeats are scattered across chromosomes and in angiosperms can constitute a majority of nuclear genomic DNA. In six diverse examples, five angiosperms and one insect, this method provides generally well-supported relationships at interspecific and intergeneric levels that agree with results from more standard phylogenetic analyses of commonly used markers. We propose that this methodology may prove especially useful in groups where there is little genetic differentiation in standard phylogenetic markers. At the same time as providing data for phylogenetic inference, this method additionally yields a wealth of data for comparative studies of genome evolution

Identifying the needs of brain tumor patients and their caregivers

The purpose of this study is to identify the needs of brain tumor patients and their caregivers to provide improved health services to these populations. Two different questionnaires were designed for patients and caregivers. Both questionnaires contained questions pertaining to three realms: disease symptoms/treatment, health care provider, daily living/finances. The caregivers’ questionnaires contained an additional domain on emotional needs. Each question was evaluated for the degree of importance and satisfaction. Exploratory analyses determined whether baseline characteristics affect responder importance or satisfaction. Also, areas of high agreement/disagreement in satisfaction between the participating patient-caregiver pairs were identified. Questions for which >50% of the patients and caregivers thought were “very important” but >30% were dissatisfied include: understanding the cause of brain tumors, dealing with patients’ lower energy, identifying healthful foods and activities for patients, telephone access to health care providers, information on medical insurance coverage, and support from their employer. In the emotional realm, caregivers identified 9 out of 10 items as important but need further improvement. Areas of high disagreement in satisfaction between participating patient-caregiver pairs include: getting help with household chores (P value = 0.006) and finding time for personal needs (P value < 0.001). This study provides insights into areas to improve services for brain tumor patients and their caregivers. The caregivers’ highest amount of burden is placed on their emotional needs, emphasizing the importance of providing appropriate medical and psychosocial support for caregivers to cope with emotional difficulties they face during the patients’ treatment process

A Stochastic Model for Microtubule Motors Describes the In Vivo Cytoplasmic Transport of Human Adenovirus

Cytoplasmic transport of organelles, nucleic acids and proteins on microtubules is usually bidirectional with dynein and kinesin motors mediating the delivery of cargoes in the cytoplasm. Here we combine live cell microscopy, single virus tracking and trajectory segmentation to systematically identify the parameters of a stochastic computational model of cargo transport by molecular motors on microtubules. The model parameters are identified using an evolutionary optimization algorithm to minimize the Kullback-Leibler divergence between the in silico and the in vivo run length and velocity distributions of the viruses on microtubules. The present stochastic model suggests that bidirectional transport of human adenoviruses can be explained without explicit motor coordination. The model enables the prediction of the number of motors active on the viral cargo during microtubule-dependent motions as well as the number of motor binding sites, with the protein hexon as the binding site for the motors