AnglerFish: a webserver for defining the geometry of α-Helices in membrane proteins

Summary: Integral membrane proteins that form helical pores and bundles constitute major drug targets, and many of their structures have been defined by crystallography and cryo-electron microscopy. The gating of channels and ligand binding of transporters generally involves changes in orientation of one or more the constituent helices in the structures. At present there is no standard easily- accessible means for defining the orientation of a helix in a membrane protein structure. AnglerFish is a web-based tool for parameterising the angles of transmembrane helices based on PDB coordinates, with the helical orientations defined by the angles “tilt” and “swing”. AnglerFish is particularly useful for defining changes in structure between different states, including both symmetric and asymmetric transitions, and can be used to quantitate differences between related structures or different subunits within the same structure

Vegetation recolonisation of abandoned agricultural terraces on Antikythera, Greece

Antikythera is a small, relatively remote Mediterranean island, lying 35 km north-west of Crete, and its few contemporary inhabitants live mainly in the small village at the only port. However, an extensive network of terraces across the island bears witness to the past importance of farming on the island, although the intensity of use of these cultivated plots has changed according to fluctuating population levels. Most recently, the rural population and intensity of cultivation have dramatically declined. Our aim is to understand the recolonisation process of agricultural land by plants after terraces are no longer used for the cultivation of crops. The results demonstrate a relatively quick pace of vegetative recolonisation, with abandoned farm land covered by dense scrub within 20 to 60 years. The archaeological implications are that, following even relatively short periods of abandonment, the landscape would have required arduous reinvestment in the removal of scrub growth, as well as the repair and construction of stone terraces, to allow cultivation once again

The application of the CERIF data format to Snowball metrics

The euroCRIS Indicators Task Group aims to develop and share best practice in the use of indicators to support research information management. One of the outputs of the group will be indicators expressed in CERIF that can re-used by CERIF-compliant software services to support consistent measurements for both national and international purposes. This Task Group will express multiple sets of indicators in CERIF, with Snowball Metrics being the first set to be tackled. The goal of the Snowball Metrics initiative is for research-intensive institutions to share their knowledge and experiences to agree best practice in evidence-based institutional strategic planning. Agreed and tested metrics “recipes”, or methodologies, are shared free of charge with the sector in the Snowball Metrics Recipe Book (www.snowballmetrics.com/metrics)1 for use by any organization, whether for public service or commercial purposes. One of the principles of Snowball Metrics is that they are system-agnostic: in other words, that although particular types of data are needed to support their calculation, the data can come from any relevant source such that the recipes are not tied to any one particular system or supplier of research information. The application of the CERIF data standard to the recipes is an important component in enabling benchmarking between institutions in a system-agnostic manner through the exchange of Snowball Metrics. CERIFication of Snowball Metrics is also expected to facilitate the endorsement of these recipes as global standards. The first set of recipes was agreed and tested by a group of universities in the United Kingdom, but the vision is that Snowball Metrics are supported by universities globally, and that multiple national groups contribute their expertise to agree how best to leverage the institutional and national data sources available, alongside proprietary data sources. The formation of Working Groups and the use of Snowball Metrics outside the United Kingdom demonstrate that the initiative is gaining global traction, and strongly indicate that the needs being addressed are widespread problems for which the sector would like to find a single answer. The universal nature of CERIF provides an important reference point to which it is expected that distinct but equivalent national data sources can be mapped and so used in international benchmarking

Domestication as innovation : the entanglement of techniques, technology and chance in the domestication of cereal crops

The origins of agriculture involved pathways of domestication in which human behaviours and plant genetic adaptations were entangled. These changes resulted in consequences that were unintended at the start of the process. This paper highlights some of the key innovations in human behaviours, such as soil preparation, harvesting and threshing, and how these were coupled with genetic ‘innovations’ within plant populations. We identify a number of ‘traps’ for early cultivators, including the needs for extra labour expenditure on crop-processing and soil fertility maintenance, but also linked gains in terms of potential crop yields. Compilations of quantitative data across a few different crops for the traits of nonshattering and seed size are discussed in terms of the apparently slow process of domestication, and parallels and differences between different regional pathways are identified. We highlight the need to bridge the gap between a Neolithic archaeobotanical focus on domestication and a focus of later periods on crop-processing activities and labour organization. In addition, archaeobotanical data provide a basis for rethinking previous assumptions about how plant genetic data should be related to the origins of agriculture and we contrast two alternative hypotheses: gradual evolution with low selection pressure versus metastable equilibrium that prolonged the persistence of ‘semi-domesticated’ populations. Our revised understanding of the innovations involved in plant domestication highlight the need for new approaches to collecting, modelling and integrating genetic data and archaeobotanical evidence

Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred CFTR-knockout mice

This article is available open access through the publisher’s website at the link below. Copyright © 2008 The American Society of Gene Therapy.Due to its early onset and severe prognosis, cystic fibrosis (CF) has been suggested as a candidate disease for in utero gene therapy. In 1997, a study was published claiming that to how transient prenatal expression of CF transmembrane conductance regulator (CFTR) from an in utero –injected adenovirus vector could achieve permanent reversal of the CF intestinal pathology in adult CF knockout mice, despite the loss of CFTR transgene expression by birth. This would imply that the underlying cause of CF is a prenatal defect for which lifelong cure can be achieved by transient prenatal expression of CFTR. Despite criticism at the time of publication, no independent verification of this contentious finding has been published so far. This is vital for the development of future therapeutic strategies as it may determine whether CF gene therapy should be performed prenatally or postnatally. We therefore reinvestigated this finding with an identical adenoviral vector and a knockout CF mouse line (CftrtmlCam) with a completely inbred genetic background to eliminate any effects due to genetic variation. After delivery of the CFTR-expressing adenovirus to the fetal mouse, both vector DNA and transgenic CFTR expression were detected in treated animals postpartum but statistically no significant difference in survival was observed between the Cftr–/– mice treated with the CFTR-adenovirus and those treated with the control vector.Sport Aiding Medical Research for Kids, the Cystic Fibrosis Trust, and the Katharine Dormandy Trust

Profile and correlates of injecting-related injuries and diseases among people who inject drugs in Australia

Introduction: People who inject drugs (PWID) commonly experience harms related to their injecting, many of which are consequences of modifiable drug use practices. There is currently a gap in our understanding of how certain injecting-related injuries and diseases (IRID) cluster together, and socio-demographic and drug use characteristics associated with more complex clinical profiles. Method: Surveys were conducted with 902 Australian PWID in 2019. Participants provided information regarding their drug use, and past month experience of the following IRID: artery injection, nerve damage, skin and soft tissue infection, thrombophlebitis, deep vein thrombosis, endocarditis, septic arthritis, osteomyelitis, and septicaemia. We performed a latent class analysis, grouping participants based on reported IRID and ran a class-weighted regression analysis to determine variables associated with class-membership. Results: One-third (34 %) of the sample reported any IRID. A 3-class model identified: 1) no IRID (73 %), moderate IRID (21 %), and 3) high IRID (6%) clusters. Re-using one`s own needles was associated with belonging to the high IRID versus moderate IRID class (ARRR = 2.38; 95 % CI = 1.04−5.48). Other factors, including daily injecting and past 6-month mental health problems were associated with belonging to moderate and high IRID classes versus no IRID class. Conclusion: A meaningful proportion of PWID reported highly complex IRID presentations distinguished by the presence of thrombophlebitis and associated with greater re-use of needles. Increasing needle and syringe coverage remains critical in addressing the harms associated with injecting drug use and expanding the capacity of low-threshold services to address less severe presentations might aid in reducing IRID amongst PWID

Opioid agonist treatment and risk of death or rehospitalization following injection drug use–associated bacterial and fungal infections: A cohort study in New South Wales, Australia

Background AU Injecting-related: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly bacterial and fungal infections are associated : with significant morbidity and mortality among people who inject drugs (PWID), and they are increasing in incidence. Following hospitalization with an injecting-related infection, use of opioid agonist treatment (OAT; methadone or buprenorphine) may be associated with reduced risk of death or rehospitalization with an injecting-related infection. Methods and findings Data came from the Opioid Agonist Treatment Safety (OATS) study, an administrative linkage cohort including all people in New South Wales, Australia, who accessed OAT between July 1, 2001 and June 28, 2018. Included participants survived a hospitalization with injecting-related infections (i.e., skin and soft-tissue infection, sepsis/bacteremia, endocarditis, osteomyelitis, septic arthritis, or epidural/brain abscess). Outcomes were all-cause death and rehospitalization for injecting-related infections. OAT exposure was classified as time varying by days on or off treatment, following hospital discharge. We used separate Cox proportional hazards models to assess associations between each outcome and OAT exposure. The study included 8,943 participants (mean age 39 years, standard deviation [SD] 11 years; 34% women). The most common infections during participants’ index hospitalizations were skin and soft tissue (7,021; 79%), sepsis/bacteremia (1,207; 14%), and endocarditis (431; 5%). During median 6.56 years follow-up, 1,481 (17%) participants died; use of OAT was associated with lower hazard of death (adjusted hazard ratio [aHR] 0.63, 95% confidence interval [CI] 0.57 to 0.70). During median 3.41 years follow-up, 3,653 (41%) were rehospitalized for injecting-related infections; use of OAT was associated with lower hazard of these rehospitalizations (aHR 0.89, 95% CI 0.84 to 0.96). Study limitations include the use of routinely collected administrative data, which lacks information on other risk factors for injecting-related infections including injecting practices, injection stimulant use, housing status, and access to harm reduction services (e.g., needle exchange and supervised injecting sites); we also lacked information on OAT medication dosages. Conclusions Following hospitalizations with injection drug use–associated bacterial and fungal infections, use of OAT is associated with lower risks of death and recurrent injecting-related infections among people with opioid use disorder

Effect of incarceration and opioid agonist treatment transitions on risk of hospitalisation with injection drug use-associated bacterial infections: A self-controlled case series in New South Wales, Australia

Background: Transitional times in opioid use, such as release from prison and discontinuation of opioid agonist treatment (OAT), are associated with health harms due to changing drug consumption practices and limited access to health and social supports. Using a self-controlled (within-person) study design, we aimed to understand if these transitions increase risks of injection drug use-associated bacterial infections. Methods: We performed a self-controlled case series among a cohort of people with opioid use disorder (who had all previously accessed OAT) in New South Wales, Australia, 2001-2018. The outcome was hospitalisation with injecting-related bacterial infections. We divided participants’ observed days into time windows related to incarceration and OAT receipt. We compared hospitalization rates during focal (exposure) windows and referent (control) windows (i.e., 5-52 weeks continuously not incarcerated or continuously receiving OAT). We estimated adjusted incidence rate ratios (aIRR) using conditional logistic regression, adjusted for time-varying confounders. Results: There were 7590 participants who experienced hospitalisation with injecting-related bacterial infections (35% female; median age 38 years; 78% hospitalised with skin and soft-tissue infections). Risk for injecting-related bacterial infections was elevated for two weeks following release from prison (aIRR 1.45; 95%CI 1.22–1.72). Risk was increased during two weeks before (aIRR 1.89; 95%CI 1.59–2.25) and after (aIRR 1.91; 95%CI 1.54–2.36) discontinuation of OAT, and during two weeks before (aIRR 3.63; 95%CI 3.13–4.22) and after (aIRR 2.52; 95%CI 2.09–3.04) OAT initiation. Conclusion: Risk of injecting-related bacterial infections varies greatly within-individuals over time. Risk is raised immediately after prison release, and around initiation and discontinuation of OAT. Social contextual factors likely contribute to excess risks at transitions in incarceration and OAT exposure