APOBEC3 versus Retroviruses, Immunity versus Invasion: Clash of the Titans

Since the identification of APOBEC3G (A3G) as a potent restriction factor of HIV-1, a tremendous amount of effort has led to a broadened understanding of both A3G and the APOBEC3 (A3) family to which it belongs. In spite of the fine-tuned viral counterattack to A3 activity, in the form of the HIV-1 Vif protein, enthusiasm for leveraging the Vif : A3G axis as a point of clinical intervention remains high. In an impressive explosion of information over the last decade, additional A3 family members have been identified as antiviral proteins, mechanistic details of the restrictive capacity of these proteins have been elucidated, structure-function studies have revealed important molecular details of the Vif : A3G interaction, and clinical cohorts have been scrutinized for correlations between A3 expression and function and viral pathogenesis. In the last year, novel and unexpected findings regarding the role of A3G in immunity have refocused efforts on exploring the potential of harnessing the natural power of this immune defense. These most recent reports allude to functions of the A3 proteins that extend beyond their well-characterized designation as restriction factors. The emerging story implicates the A3 family as not only defense proteins, but also as participants in the broader innate immune response

Arctostaphylos heath community ecology in the Burren,Western Ireland

Arctostaphylo-Dryasetum is a rare sub-type of Alpine and Boreal Heath which is known to occur only in Ireland on the limestone karst Burren, in County Clare. Relevés were taken across the Burren region and three groups were distinguished: Empetrum nigrum group; Erica cinerea group, Juniperus communis group. Altitude and soil conditions were found to be the main ecological factors responsible for the variation in the data set, especially pH, and the organic and mineral content. Winter grazing appears to maintain this habitat. In some areas Calluna vulgaris has encroached on the rarer plant species cutting trials are underway in an attempt to restore the habitat to good conservation status

Professional Learning Community: Thriving While Facing the Challenges of Faculty Life Together

Researchers have begun to focus attention on the participation of teacher educators in communities of practice (CoPs) and the role that participation plays in improving the quality of teacher education. This case study explores an inter-university CoP (sustained for over 10 years) that includes four faculty members at three universities, who work collaboratively on teacher education program development (e.g., accreditation), research, and service. This exploration is situated in the literature on CoPs, professional capital, and teacher educators’ involvement in CoPs. In this paper the evolution of this inter-university CoP and each CoP member’s personal meaning is shared. Key influences of this involvement in our professional learning (PL) and suggestions for teacher educators’ PL as members of an academic community are offered

Should there be a future for Tablet PCs in schools?

Tablet PCs are a relatively new format of computer, which seem to offer features which may be beneficial to schools. The uptake of Tablet PCs by schools has been somewhat limited, not least due to their greater cost than laptops of a 'similar' specification. This paper explores the key question of the extent to which schools should be investing in Tablet PCs, if at all, in preference to other formats of fully functional PCs, drawing on evidence from a Becta funded evaluation of the use of Tablet PCs in schools in England conducted in 2004-2005. The Computer Practice Framework was used to develop a set of questions which helped structure a meta-analysis of the data from 12 case studies that formed part of this evaluation. The methodology used and some limitations of the evaluation are outlined, and the key findings are described. The paper concludes that Tablet PCs do appear to offer significant potential to schools, though this potential was not being fully realised in most of the case study schools. A number of specific circumstances in which Tablet PCs do appear to be the most cost effective option are also identified

Spin-Imbalance in a One-Dimensional Fermi Gas

Superconductivity and magnetism generally do not coexist. Changing the relative number of up and down spin electrons disrupts the basic mechanism of superconductivity, where atoms of opposite momentum and spin form Cooper pairs. Nearly forty years ago Fulde and Ferrell and Larkin and Ovchinnikov proposed an exotic pairing mechanism (FFLO) where magnetism is accommodated by formation of pairs with finite momentum. Despite intense theoretical and experimental efforts, however, polarized superconductivity remains largely elusive. Here we report experimental measurements of density profiles of a two spin mixture of ultracold 6Li atoms trapped in an array of one dimensional (1D) tubes, a system analogous to electrons in 1D wires. At finite spin imbalance, the system phase separates with an inverted phase profile in comparison to the three-dimensional case. In 1D we find a partially polarized core surrounded by wings composed of either a completely paired BCS superfluid or a fully polarized Fermi gas, depending on the degree of polarization. Our observations are in quantitative agreement with theoretical calculations in which the partially polarized phase is found to be a 1D analogue of the FFLO state. This study demonstrates how ultracold atomic gases in 1D may be used to create non-trivial new phases of matter, and also paves the way for direct observation and further study of the FFLO phase.Comment: 30 pages, 7 figure

The importance of communication and involvementin decision-making: A study in Ireland exploring birthsatisfaction using the Birth Satisfaction Scale-Revised (BSS-R)

Introduction:Evaluation in healthcare services has become a priority, globally1. The Government of Ireland has highlighted the importance of stakeholder engagement to identify the needs of women in the design and delivery of high-quality health services, driven by necessity rather than financial ability2. The Birth Satisfaction Scale-Revised (BSS-R), an internationally validated tool, and recommended for measuring childbirth satisfaction by the International Consortium for Health Outcomes Measurement (ICHOM)3; however, it has yet to be considered in the Irish context. The aim of the study was to explore birth satisfaction with a sample of new mothers in Ireland.Methods:A mixed-methods study was conducted including a survey that involved collection of data from the BSS-R 10-item questionnaire from 307 mothers over an 8-week period in 2019, in one urban maternity hospital in Ireland. Quantitative and qualitative data were collected. Qualitative data from the free-text comments of the survey questions were analyzed using content analysis.Results:Overall, women reported positive relationships with their care providers and were satisfied with the communication and support they received, as well as high levels of control and choice. Postnatal care, however, was highlighted as being less satisfactory with staffing levels described as inadequate.Conclusions:Understanding women’s birth experiences and what is important to them could facilitate midwives and other health professionals to improve the quality of their care and develop guidelines and policies that focus on women and their families’ needs. The vast majority of women rated their birthing experience as extremely positive. The main elements of care that contributed to a positive birthing experience for women were quality relationships with clinicians, choice and control, and emotional safety

A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis : First-in-human trial of ChAd63-KH

BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. CONCLUSION: The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. TRIAL REGISTRATION: This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359)

Lake isotope records of the 8200-year cooling event in western Ireland: Comparison with model simulations

The early Holocene cooling, which occurred around 8200 calendar years before present, was a prominent abrupt event around the north Atlantic region. Here, we investigate the timing, duration, magnitude and regional coherence of the event as expressed in carbonate oxygen-isotope records from three lakes on northwest Europe's Atlantic margin in western Ireland, namely Loch Avolla, Loch Gealáin and Lough Corrib. An abrupt negative oxygen-isotope excursion lasted about 200 years. Comparison of records from three sites suggests that the excursion was primarily the result of a reduction of the oxygen-isotope values of precipitation, which was likely caused by lowered air temperatures, possibly coupled with a change in atmospheric circulation. Comparison of records from two of the lakes (Loch Avolla and Loch Gealáin), which have differing bathymetries, further suggests a reduction in evaporative loss of lake water during the cooling episode. Comparison of climate model experiments with lake-sediment isotope data indicates that effective moisture may have increased along this part of the northeast Atlantic seaboard during the 8200-year climatic event, as lower evaporation compensated for reduced precipitation

Genetic improvement of tomato by targeted control of fruit softening

Controlling the rate of softening to extend shelf life was a key target for researchers engineering genetically modified (GM) tomatoes in the 1990s, but only modest improvements were achieved. Hybrids grown nowadays contain 'non-ripening mutations' that slow ripening and improve shelf life, but adversely affect flavor and color. We report substantial, targeted control of tomato softening, without affecting other aspects of ripening, by silencing a gene encoding a pectate lyase

Ape Conservation Physiology: Fecal Glucocorticoid Responses in Wild Pongo pygmaeus morio following Human Visitation

Nature-based tourism can generate important revenue to support conservation of biodiversity. However, constant exposure to tourists and subsequent chronic activation of stress responses can produce pathological effects, including impaired cognition, growth, reproduction, and immunity in the same animals we are interested in protecting. Utilizing fecal samples (N = 53) from 2 wild habituated orangutans (Pongo pygmaeus morio) (in addition to 26 fecal samples from 4 wild unhabituated orangutans) in the Lower Kinabatangan Wildlife Sanctuary of Sabah, Malaysian Borneo, we predicted that i) fecal glucocorticoid metabolite concentrations would be elevated on the day after tourist visitation (indicative of normal stress response to exposure to tourists on the previous day) compared to samples taken before or during tourist visitation in wild, habituated orangutans, and ii) that samples collected from habituated animals would have lower fecal glucocorticoid metabolites than unhabituated animals not used for tourism. Among the habituated animals used for tourism, fecal glucocorticoid metabolite levels were significantly elevated in samples collected the day after tourist visitation (indicative of elevated cortisol production on the previous day during tourist visitation). Fecal glucocorticoid metabolite levels were also lower in the habituated animals compared to their age-matched unhabituated counterparts. We conclude that the habituated animals used for this singular ecotourism project are not chronically stressed, unlike other species/populations with documented permanent alterations in stress responses. Animal temperament, species, the presence of coping/escape mechanisms, social confounders, and variation in amount of tourism may explain differences among previous experiments. Acute alterations in glucocorticoid measures in wildlife exposed to tourism must be interpreted conservatively. While permanently altered stress responses can be detrimental, preliminary results in these wild habituated orangutans suggest that low levels of predictable disturbance can likely result in low physiological impact on these animals