Investigating a New Generation of Ribozymes in Order to Target HCV

For a long time nucleic acid-based approaches directed towards controlling the propagation of Hepatitis C Virus (HCV) have been considered to possess high potential. Towards this end, ribozymes (i.e. RNA enzymes) that specifically recognize and subsequently catalyze the cleavage of their RNA substrate present an attractive molecular tool. Here, the unique properties of a new generation of ribozymes are taken advantage of in order to develop an efficient and durable ribozyme-based technology with which to target HCV (+) RNA strands. These ribozymes resulted from the coupling of a specific on/off adaptor (SOFA) to the ribozyme domain derived from the Hepatitis Delta Virus (HDV). The former switches cleavage activity “on” solely in the presence of the desired RNA substrate, while the latter was the first catalytic RNA reported to function naturally in human cells, specifically in hepatocytes. In order to maximize the chances for success, a step-by-step approach was used for both the design and the selection of the ribozymes. This approach included the use of both bioinformatics and biochemical methods for the identification of the sites possessing the greatest potential for targeting, and the subsequent in vitro testing of the cleavage activities of the corresponding SOFA-HDV ribozymes. These efforts led to a significant improvement in the ribozymes' designs. The ability of the resulting SOFA-HDV ribozymes to inhibit HCV replication was further examined using a luciferase-based replicon. Although some of the ribozymes exhibited high levels of cleavage activity in vitro, none appears to be a potential long term inhibitor in cellulo. Analysis of recent discoveries in the cellular biology of HCV might explain this failure, as well as provide some ideas on the potential limits of using nucleic acid-based drugs to control the propagation of HCV. Finally, the above conclusions received support from experiments performed using a collection of SOFA-HDV ribozymes directed against HCV (−) strands

Creative haptics: an evaluation of a haptic tool for non-sighted and visually impaired design students, studying at a distance

Design students who are blind or sight-impaired face distinct challenges when studying a visually centric discipline such as design practice. Students who are sighted use computer-aided design (CAD) which is presented via high definition using a PC mouse. However, design students who are blind or sight-impaired are not able to use visual display technology; therefore, this creates a barrier to access for this community. The aim of this study is to present a haptic prototype trial (Haptic Application Prototype Test [HAPT]) designed to assist design students who are blind/sight-impaired to interact with prototype assembly at the Open University (OU). The study specifically assessed the user feedback and the efficacy of access to CAD interface through the affordances of the haptic interface. The experiment included two groups of participants: one group included students who were blind and sight-impaired and the second group students who were classed fully sighted. Both groups were tested in two conditions of haptic engagement – manual and virtual. The parameters examined were (a) time – set at an industry-recognized time taken to assemble a ‘sketch model’ or prototype, and (b) ncollision – the number of collisions created by a collision algorithm which calculated any random collisions with the virtual environment or objects therein. Quantitative results showed that there was little statistical difference between time and a between-group test. From this we can imply that the haptic interface had offered equal access to CAD for people in the trial who were sighted and blind/sight-impaired indiscriminate of their sight acuity. Further future work using HAPT could be developed to a wider audience and a larger more diverse range of sight-impaired users. Future work will focus on new explorations of teaching using of haptics for greater immersion for distance learners at the OU science, technology, engineering and mathematics (STEM) labs

Trade union strategies in the age of austerity: the Romanian public sector in comparative perspective

This article examines the impact of the economic crisis and its aftermath on collective bargaining, by comparing reactions to austerity policies of trade unions in healthcare and education in Romania. We develop an encompassing theoretical framework that links strategies used by trade unions with power resources, costs and union democracy. In a tight labour market generated by the massive emigration of doctors, unions in healthcare have successfully deployed their resources to advance their interests and obtain significant wage increases and better working conditions. We also show that in the aftermath of the crisis, healthcare trade unions have redefined their strategies and adopted a more militant stance based on a combination of local strikes, strike threats and temporary alliances with various stakeholders. By comparison, we find that unions in the education sector have adopted less effective strategies built around negotiations with governments combined with national-level militancy

Long-term soil water limitation and previous tree vigor drive local variability of drought-induced crown dieback in Fagus sylvatica.

Ongoing climate warming is increasing evapotranspiration, a process that reduces plant-available water and aggravates the impact of extreme droughts during the growing season. Such an exceptional hot drought occurred in Central Europe in 2018 and caused widespread defoliation in mid-summer in European beech (Fagus sylvatica L.) forests. Here, we recorded crown damage in 2021 in nine mature even-aged beech-dominated stands in northwestern Switzerland along a crown damage severity gradient (low, medium, high) and analyzed tree-ring widths of 21 mature trees per stand. We aimed at identifying predisposing factors responsible for differences in crown damage across and within stands such as tree growth characteristics (average growth rates and year-to-year variability) and site-level variables (mean canopy height, soil properties). We found that stand-level crown damage severity was strongly related to soil water availability, inferred from tree canopy height and plant available soil water storage capacity (AWC). Trees were shorter in drier stands, had higher year-to-year variability in radial growth, and showed higher growth sensitivity to moisture conditions of previous late summer than trees growing on soils with sufficient AWC, indicating that radial growth in these forests is principally limited by soil water availability. Within-stand variation of post-drought crown damage corresponded to growth rate and tree size (diameter at breast height, DBH), i.e., smaller and slower-growing trees that face more competition, were associated with increased crown damage after the 2018 drought. These findings point to tree vigor before the extreme 2018 drought (long-term relative growth rate) as an important driver of damage severity within and across stands. Our results suggest that European beech is less likely to be able to cope with future climate change-induced extreme droughts on shallow soils with limited water retention capacity

N/P addition is more likely than N addition alone to promote a transition from moss-dominated to graminoid-dominated tundra in the High-Arctic

Nutrient availability for tundra vegetation could change drastically due to increasing temperatures and frequency of nitrogen deposition in the Arctic. Few studies have simultaneously examined the response of plant communities to these two pressures over a long period. This study aims to assess which driver between increasing nitrogen (N) and phosphorus (P) availability through global warming and increasing N availability alone via N deposition is more likely to transform arctic wetland vegetation and whether there is a time lag in this response. An annual fertilization experiment simulating these nutrient inputs was conducted for 17 years in the Canadian High-Arctic to assess the impact on aboveground net primary productivity, floristic composition, and plant nutrient concentration. While the primary productivity of mosses remains unchanged by fertilization after 17 years, productivity of graminoids was increased slightly by N addition (36% increase at the highest dose). In contrast, the primary productivity of graminoids increased strongly with N/P addition (over 227% increase). We noted no difference in graminoid productivity between the 2nd and 5th year of the experiment, but we observed a 203% increase between the 5th and 17th year in the N/P addition treatments. We also noted a 49% decrease in the total moss cover and an 155% increase in the total graminoid cover between the 2nd and 17th year of N/P addition. These results indicate that the impact of warming through increased N/P availability was greater than those of N deposition alone (N addition) and promoted the transition from a moss-dominated tundra to a graminoid-dominated tundra. However, this transition was subject to a time lag of up to 17 years, suggesting that increased productivity of graminoids resulted from a release of nutrients via the decomposition of lower parts of the moss mat. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

New qnr Gene Cassettes Associated with Superintegron Repeats in Vibrio cholerae O1

A novel qnr determinant emerged in ciprofloxacin-resistant Vibrio cholerae O1 from the Amazon region of Brazil. This qnrVC1 was in a typical class 1 integron. Its attC showed 89% identity with V. parahaemolyticus superintegron repeats. Analysis showed V. cholerae O1 carrying qnrVC2 associated with a V. cholerae superintegron repeat

A molecular insight into algal-oomycete warfare : cDNA analysis of Ectocarpus siliculosus infected with the basal oomycete Eurychasma dicksonii

Peer reviewedPublisher PD

Towards a pan-Arctic inventory of the species diversity of the macro- and megabenthic fauna of the Arctic shelf seas

Although knowledge of Arctic seas has increased tremendously in the past decade, benthic diversity was investigated at regional scales only, and no attempt had been made to examine it across the entire Arctic. We present a first pan-Arctic account of the species diversity of the macro- and megabenthic fauna of the Arctic marginal shelf seas. It is based on an analysis of 25 published and unpublished species-level data sets, together encompassing 14 of the 19 marine Arctic shelf ecoregions and comprising a total of 2636 species, including 847 Arthropoda, 668 Annelida, 392 Mollusca, 228 Echinodermata, and 501 species of other phyla. For the four major phyla, we also analyze the differences in faunal composition and diversity among the ecoregions. Furthermore, we compute gross estimates of the expected species numbers of these phyla on a regional scale. Extrapolated to the entire fauna and study area, we arrive at the conservative estimate that 3900 to 4700 macro- and megabenthic species can be expected to occur on the Arctic shelves. These numbers are smaller than analogous estimates for the Antarctic shelf but the difference is on the order of about two and thus less pronounced than previously assumed. On a global scale, the Arctic shelves are characterized by intermediate macro- and megabenthic species numbers. Our preliminary pan-Arctic inventory provides an urgently needed assessment of current diversity patterns that can be used by future investigations for evaluating the effects of climate change and anthropogenic activities in the Arctic

Being a Self-Employed Older Woman: From Discrimination to Activism

This article presents an autobiographical account of an older woman’s lived experience of self-employment. Little is known about women who experience ongoing self-employment into their 50s and beyond. Shoshanna’s personal narrative describes her experiences and the challenges she has faced as she reflects upon her attempts to grow and sustain her business and the implications of ageism and gender inequality in laying a claim to entrepreneurship. The narrative proceeds to reflect on her activist work, as it is constructed through the creation of a social enterprise to support older people. Shoshanna’s narrative provides valuable insights into the intersection of age and gender in self-employment moving from discrimination to active support

Hydrological regime and plant functional traits jointly mediate the influence of Salix spp. on soil organic carbon stocks in a High Arctic tundra

Evidence points out that increasing plant productivity associated with greater erect shrub abundance alters soil organic carbon (SOC) stocks in the Arctic. However, the underlying plant economic traits remain poorly examined, which limits our understanding of plant–environment interactions driving tundra carbon cycling. We explored how erect shrub abundance leads to SOC variation in a High Arctic tundra (Bylot Island, Nunavut, Canada), where the only erect shrub, Salix richardsonii, has settled along currently active and abandoned channel zones of alluvial fans. The effects of vegetation and local environmental changes on SOC were evaluated through a paired sampling of soil materials and plant aboveground functional traits associated with plant carbon supply and nutrient demand processes. The occurrence of S. richardsonii, characterized by a tenfold increase in aboveground biomass, induced a 28% increase in SOC compared to adjacent plots dominated by prostrate shrubs and graminoids. Yet, this vegetation effect was solely observed along active channels, where higher SOC was associated with greater leaf and stem biomass. A path analysis showed that shrub leaf area index and total leaf nutrient content best represented plant carbon supply and nutrient demand dynamics, respectively, and jointly regulated SOC variation. This study underscores that vegetation structural changes associated with increasing erect shrub abundance in the Arctic can promote soil organic carbon storage, but that this pattern may be mediated by strong plant–environment interactions. Accounting for changes in functional traits driving plant carbon supply and nitrogen demand proves important for a better mechanistic understanding of how shrubification impacts tundra carbon cycling