Epigenetic regulation of the telomerase gene promoters

Epigenetic mechanisms have been implicated in the regulation of telomerase gene expression and here we show that specific modifications within the chromatin environment of the hTR and hTERT promoters correlate with expression of hTR and hTERT in ALT, normal and telomerase-positive tumour cell lines. Lack of expression of hTR and hTERT is associated with repressive histone modification, while, hTR and hTERT expression is associated permissive histone modifications. Methylation of lysine 20 H4 was not linked to gene expression but instead was specific to the hTR and hTERT promoters of ALT cells providing an insight into the differences between ALT and telomerase-positive cells as well as a novel marker for the ALT phenotype. Basal transcription machinery dynamics were also shown to be different between normal and cancer cells at the telomerase gene promoters. Modulation of the chromatin environment was also shown to cause re-expression or increased expression of hTR and hTERT further supporting the role of the chromatin environment in controlling telomerase gene expression. Epigenetic mechanisms are also shown to be involved in the repression of hTERT transcription in human mesenchymal stem cell (hMSCs) and modulation of the chromatin environment is shown to allow re-expression of hTERT expression, while the disruption of telomerase gene expression in human haematopoietic stem cells (hHSCs) in chronic myeloid leukaemia (CML) and the role of the chromatin environment was also studied. These data establishes how epigenetic mechanisms can contribute to transcriptional regulation of telomerase and also highlights the potential importance of epigenetics in senescence and tumourigenicity

Mesoscale Hydrographic Variability in the Vicinity of Points Conception and Arguello During April May 1983: The OPUS 1983 Experiment

In April and May 1983, interdisciplinary oceanographic observations were made of upwelling events in the Point Conception area off southern California. The principal objective was to observe the structure and time dependence of the upwelling system. To accomplish this, two ships, two aircraft, moorings, drogues, and satellite imagery were all included in the observational effort. During the intensive measurement period three main upwelling events and two intervening relaxation or downwelling intervals were sampled during what was a period of overall longer-term sea surface warming. Surface temperatures during upwelling were as low as 10.5°C in the upwelling center between Point Arguello and Point Conception, while during periods of nonupwelling winds, temperatures reached 14°–15°C in the same area. The upwelling center was also a source of higher-salinity water (33.7‰) relative to the offshore waters that were anomalously fresh (33.3‰). Upwelling was observed off Point Arguello, Point Conception, and the area between with a possible lag of up to a day at Point Conception relative to the other areas. The upwelling plume as observed by surface mapping and remote sensing tended to move in a variety of directions from SE to SW. Part of the movement was usually into the Santa Barbara Channel, but other parts of the plume occasionally moved southwestward. There was no obvious correlation of plume direction with the wind. During relaxation events the entire region was covered by a 10- to 20-m-thick warm (14°–16°C), fresh

Low-cost automated vectors and modular environmental sensors for plant phenotyping

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. High-throughput plant phenotyping in controlled environments (growth chambers and glasshouses) is often delivered via large, expensive installations, leading to limited access and the increased relevance of “affordable phenotyping” solutions. We present two robot vectors for automated plant phenotyping under controlled conditions. Using 3D-printed components and readily-available hardware and electronic components, these designs are inexpensive, flexible and easily modified to multiple tasks. We present a design for a thermal imaging robot for high-precision time-lapse imaging of canopies and a Plate Imager for high-throughput phenotyping of roots and shoots of plants grown on media plates. Phenotyping in controlled conditions requires multi-position spatial and temporal monitoring of environmental conditions. We also present a low-cost sensor platform for environmental monitoring based on inexpensive sensors, microcontrollers and internet-of-things (IoT) protocols

Comparing Biological Motion Perception in Two Distinct Human Societies

Cross cultural studies have played a pivotal role in elucidating the extent to which behavioral and mental characteristics depend on specific environmental influences. Surprisingly, little field research has been carried out on a fundamentally important perceptual ability, namely the perception of biological motion. In this report, we present details of studies carried out with the help of volunteers from the Mundurucu indigene, a group of people native to Amazonian territories in Brazil. We employed standard biological motion perception tasks inspired by over 30 years of laboratory research, in which observers attempt to decipher the walking direction of point-light (PL) humans and animals. Do our effortless skills at perceiving biological activity from PL animations, as revealed in laboratory settings, generalize to people who have never before seen representational depictions of human and animal activity? The results of our studies provide a clear answer to this important, previously unanswered question. Mundurucu observers readily perceived the coherent, global shape depicted in PL walkers, and experienced the classic inversion effects that are typically found when such stimuli are turned upside down. In addition, their performance was in accord with important recent findings in the literature, in the abundant ease with which they extracted direction information from local motion invariants alone. We conclude that the effortless, veridical perception of PL biological motion is a spontaneous and universal perceptual ability, occurring both inside and outside traditional laboratory environments

Long-Term Quality of Life Improvement in Subjects with Healed Erosive Esophagitis: Treatment with Lansoprazole

Gastroesophageal reflux disease (GERD) is a chronic symptomatic condition and may be associated with erosive esophagitis (EE). Considerable data on the long-term maintenance of healing of EE are available, but data on long-term GERD symptom prevention and patient quality of life (QOL) are limited. To investigate QOL in subjects with healed EE who received 12 months of double-blind maintenance treatment with lansoprazole or ranitidine, followed by long-term open-label lansoprazole therapy to prevent recurrence of EE. Subjects with healed EE received 12 months of double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily, followed by dose-titrated, open-label lansoprazole therapy for up to 82 months. During double-blind treatment (n = 206), lansoprazole-treated patients showed significantly (P ≤ 0.05) greater improvements than ranitidine-treated patients in the frequency, severity, and ‘bothersomeness’ of heartburn, the symptom index, problems of activity limitation, eating and drinking problems, symptom problems, health distress, and social functioning. During dose-titrated, open-label treatment (n = 195), all disease-specific QOL scales except sleep improved significantly (P < 0.001) from open-label baseline at each time-point. Maintenance treatment with lansoprazole for 12 months in healed EE subjects produced significantly greater improvements in QOL indicators than ranitidine. These improvements were sustained during dose-titrated, open-label lansoprazole treatment

Assessing the value of intangible benefits of property level flood risk adaptation (PLFRA) measures

© 2015, Springer Science+Business Media Dordrecht. Studies in the UK and elsewhere have identified that flooding can result in diverse impacts, ranging from significant financial costs (tangible) to social (intangible) impacts on households. At the same time, it is now clear that large-scale flood defence schemes are not the panacea to flood risk, and there is an increasing responsibility on property owners to protect their own properties. Hence, there is an emerging expectation for homeowners to take action in the form of investing in property level flood risk adaptation (PLFRA) measures to protect their properties. However, hitherto the level of uptake of such measures remains very low. The tangible financial benefits of investing in PLFRA measures are generally well understood and have been demonstrated to be cost beneficial for many properties at risk from frequent flooding. Importantly, these estimates tend to take little account of the value of the intangible benefits of PLFRA measures and therefore may be under estimating their full benefits. There remains a need to develop an improved understanding of these intangible benefits, and this research sets out to bridge this knowledge gap. Based on a synthesis of the literature, the contingent valuation method was selected as a means to value intangible impacts of flooding on households. A questionnaire survey of homeowners affected in the 2007 flooding was employed to elicit willingness to pay (WTP) values to avoid the intangible impacts of flooding on their households. The analysis of the questionnaire survey data revealed that the average WTP per household per year to avoid intangible flood impacts was £653. This therefore represents the value of the intangible benefits of investing in PLFRA measures and is significantly higher than previously estimated. This research builds on previous research in suggesting a higher value to the intangible impacts of flooding on households by assessing wider range of intangible impacts and focussing on more experienced individuals. Furthermore, the research indicates that factors which influence the WTP values were principally stress of flood, worrying about loss of house values, worrying about future flooding and age of respondents, with income showing a weak correlation. The establishment of a new value for the intangible impacts of flooding on households in the UK is helpful in the domain of flood risk management when evaluating the total benefits (tangible and intangible) of investing in flood protection measures, thus providing a robust assessment for decision-making on flood adaptation measures at an individual property level

Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Errors in the measurement of voltage-activated ion channels in cell-attached patch-clamp recordings

Patch-clamp recording techniques have revolutionized understanding of the function and sub-cellular location of ion channels in excitable cells. The cell-attached patch-clamp configuration represents the method of choice to describe the endogenous properties of voltage-activated ion channels in the axonal, somatic and dendritic membrane of neurons, without disturbance of the intracellular milieu. Here, we directly examine the errors associated with cell-attached patch-clamp measurement of ensemble ion channel activity. We find for a number of classes of voltage-activated channels, recorded from the soma and dendrites of neurons in acute brain-slices and isolated cells, that the amplitude and kinetics of ensemble ion channel activity recorded in cell-attached patches is significantly distorted by transmembrane voltage changes generated by the flow of current through the activated ion channels. We outline simple error–correction procedures that allow a more accurate description of the density and properties of voltage-activated channels to be incorporated into computational models of neurons

Curiosity, place and wellbeing: encouraging place-specific curiosity as a "way to wellbeing'

This paper advances understandings of relationships between wellbeing and place by exploring one mechanism by which place is mobilised in the pursuit of wellbeing: the cultivation and practice of curiosity. It does so through discussion of projects funded through the Decade of Health and Wellbeing in Liverpool, England. This scheme advances ‘five ways to wellbeing,’ one of which – ‘take notice’ – encourages curiosity in and about places. Three projects – memory boxes for people living with dementia; a community garden in an area experiencing socio-economic deprivation; and an urban photography project involving veterans – form the case studies on which this paper is based. We focus on two related sets of practices and approaches to curiosity: (1) learning to see places differently; (2) focussing on the micro-geographies of place – literally, curiosities – such as found objects. These practices suggest ways in which ordinary places may be a catalyst for curiosity in ways that may benefit both individual and collective forms of wellbeing. This allows us to see and understand place and wellbeing in relational terms. In so doing, this paper contributes to conceptual debates about wellbeing, place and curiosity, and the relationships between these