Homeotic genes controlling flower development in Antirrhinum

In order to study genes controlling flower development, we have carried out an extensive transposon-mutagenesis experiment in Antirrhinum majus. More than 15 independent homeotic mutations were obtained, allowing three categories of genes to be defined. The first includes floricaula (flo), a primary gene required for the initiation of the floral developmental pathway. In the absence of the wild-type flo product, proliferating inflorescence meristems arise in place of flowers. The flo gene has been isolated and shown to be expressed transiently in a subset of organ primordia in the floral meristem. The second category includes genes that affect the identity, and also sometimes the number, of whorls of organs in the flower. These genes act in overlapping domains so that each whorl has a distinct combination of gene functions, suggesting a model for the genetic control of whorl identity and number. Genes of the third category control differences between organs in the same whorl and hence the overall symmetry of the flower. We discuss how the basic plan of the flower and inflorescence may arise through the interactions between the three categories of genes

A ubiquitin carboxyl extension protein secreted from a plant-parasitic nematode Globodera rostochiensis is cleaved in planta to promote plant parasitism

Nematode effector proteins originating from esophageal gland cells play central roles in suppressing plant defenses and in formation of the plant feeding cells that are required for growth and development of cyst nematodes. A gene (GrUBCEP12) encoding a unique ubiquitin carboxyl extension protein (UBCEP) that consists of a signal peptide for secretion, a mono-ubiquitin domain, and a 12 amino acid carboxyl extension protein (CEP12) domain was cloned from the potato cyst nematode Globodera rostochiensis. This GrUBCEP12 gene was expressed exclusively within the nematode\u27s dorsal esophageal gland cell, and was up-regulated in the parasitic second-stage juvenile, correlating with the time when feeding cell formation is initiated. We showed that specific GrUBCEP12 knockdown via RNA interference reduced nematode parasitic success, and that over-expression of the secreted GrΔSPUBCEP12 protein in potato resulted in increased nematode susceptibility, providing direct evidence that this secreted effector is involved in plant parasitism. Using transient expression assays in Nicotiana benthamiana, we found that GrΔSPUBCEP12 is processed into free ubiquitin and a CEP12 peptide (GrCEP12) in planta, and that GrCEP12 suppresses resistance gene-mediated cell death. A target search showed that expression of RPN2a, a gene encoding a subunit of the 26S proteasome, was dramatically suppressed in GrΔSPUBCEP12 but not GrCEP12 over-expression plants when compared with control plants. Together, these results suggest that, when delivered into host plant cells, GrΔSPUBCEP12 becomes two functional units, one acting to suppress plant immunity and the other potentially affecting the host 26S proteasome, to promote feeding cell formation

Evolution of floral symmetry

Flowers can be classified into two basic types according to their symmetry: regular flowers have more than one plane of symmetry and irregular flowers have only a single plane of symmetry. The irregular condition is thought to have evolved many times independently from the regular one: most commonly through the appearance of asymmetry along the dorso-ventral axis of the flower. In most cases, the irregular condition is associated with a particular type of inflorescence architecture. To understand the molecular mechanism and evolutionary origin of irregular flowers, we have been investigating genes controlling asymmetry in Antirrhinum. Several mutations have been described in Antirrhinum, a species with irregular flowers, that reduce or eliminate asymmetry along the dorso-ventral axis. We describe the nature of these mutations and how they may be used to analyse the molecular mechanisms underlying floral evolution

Evolution of flower color pattern through selection on regulatory small RNAs

Small RNAs (sRNAs) regulate genes in plants and animals. Here, we show that population-wide differences in color patterns in snapdragon flowers are caused by an inverted duplication that generates sRNAs. The complexity and size of the transcripts indicate that the duplication represents an intermediate on the pathway to microRNA evolution. The sRNAs repress a pigment biosynthesis gene, creating a yellow highlight at the site of pollinator entry. The inverted duplication exhibits steep clines in allele frequency in a natural hybrid zone, showing that the allele is under selection. Thus, regulatory interactions of evolutionarily recent sRNAs can be acted upon by selection and contribute to the evolution of phenotypic diversity

Water-Soluble Organic Composition of the Arctic Sea Surface Microlayer and Association with Ice Nucleation Ability

Organic matter in the sea surface microlayer (SML) may be transferred to the atmosphere as sea spray and hence influence the composition and properties of marine aerosol. Recent work has demonstrated that the SML contains material capable of heterogeneously nucleating ice, but the nature of this material remains largely unknown. Water-soluble organic matter was extracted from SML and underlying seawater from the Arctic and analyzed using a combination of mass spectrometric approaches. High performance liquid chromatography-ion trap mass spectrometry (LC-IT-MS), and Fourier transform ion cyclotron resonance MS (FT-ICR-MS), showed seawater extracts to be compositionally similar across all stations, whereas microlayer extracts had a different and more variable composition. LC-IT-MS demonstrated the enrichment of particular ions in the microlayer. Ice nucleation ability (defined as the median droplet freezing temperature) appeared to be related to the relative abundances of some ions, although the extracts themselves did not retain this property. Molecular formulas were assigned using LC-quadrupole time-of-flight MS (LC-TOF-MS2) and FT-ICR-MS. The ice nucleation tracer ions were associated with elevated biogenic trace gases, and were also observed in atmospheric aerosol collected during the summer, but not early spring suggesting a biogenic source of ice nuclei in the Arctic microlayer

Ecophysiology of seed dormancy and the control of germination in early spring-flowering Galanthus nivalis and Narcissus pseudonarcissus (Amaryllidaceae)

Seed dormancy induction and alleviation in the winter-flowering moist temperate woodland species Galanthus nivalis and Narcissus pseudonarcissus are complex and poorly understood. Temperature, light and desiccation were investigated to elucidate their role in the germination ecophysiology of these species. Outdoor and laboratory experiments simulating different seasonal temperatures, seasonal durations, and temperature fluctuations; the presence of light during different seasons; and intermittent drying (during the summer period) over several ‘years’ investigated the importance of these factors in germination. Warm summer-like temperatures (20°C) were necessary for germination at subsequent cooler autumn-like temperatures (greatest at 15°C in G. nivalis and 10°C in N. pseudonarcissus). As the warm temperature duration increased so did germination at subsequent cooler temperatures; further germination occurred in subsequent ‘years’ at cooler temperatures following a second, and also third, warm period. Germination was significantly greater in darkness, particularly in G. nivalis. Dormancy increased with seed maturation period in G. nivalis, because seeds extracted from green capsules germinated more readily than those from yellow. Desiccation increased dormancy in an increasing proportion of N. pseudonarcissus seeds the later they were dried in ‘summer’. Seed viability was only slightly reduced by desiccation in N. pseudonarcissus but was poor and variable in G. nivalis. Shoot formation occurred both at the temperature at which germination was greatest and also if 5°C cooler. In summary, continuous hydration of seeds of both species during warm summer-like temperatures results in the gradual release of seed dormancy; thereafter, darkness and cooler temperatures promote germination. Cold temperatures, increased seed maturity (G. nivalis), and desiccation (N. pseudonarcissus) increase dormancy while light inhibits germination

Safetxt: a safer sex intervention delivered by mobile phone messaging on sexually transmitted infections (STI) among young people in the UK - protocol for a randomised controlled trial.

INTRODUCTION: Young people aged 16 to 24 have the highest prevalence of genital chlamydia and gonorrhoea compared with other age groups and re-infection rates following treatment are high. Long-term adverse health effects include subfertility and ectopic pregnancy, particularly among those with repeated infections. We developed the safetxt intervention delivered by text message to reduce sexually transmitted infection (STI) by increasing partner notification, condom use and (STI) testing among young people in the UK. METHODS AND ANALYSIS: A single-blind randomised trial to reliably establish the effect of the safetxt intervention on chlamydia and gonorrhoea infection at 1 year. We will recruit 6250 people aged 16 to 24 years who have recently been diagnosed with chlamydia, gonorrhoea or non-specific urethritis from health services in the UK. Participants will be allocated to receive the safetxt intervention (text messages designed to promote safer sexual health behaviours) or to receive the control text messages (monthly messages asking participants about changes in contact details) by an automated remote online randomisation system. The primary outcome will be the cumulative incidence of chlamydia and gonorrhoea infection at 1 year assessed by nucleic acid amplification tests. Secondary outcomes include partner notification, correct treatment of infection, condom use and STI testing prior to sex with new partners. ETHICS AND DISSEMINATION: Ethics approval was obtained from NHS Health Research Authority - London - Riverside Research Ethics Committee (REC reference: 15/LO/1665) and the London School of Hygiene & Tropical Medicine. We will submit the results of the trial for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: International Standard Randomised Controlled Trials Number: ISRCTN64390461. Registered on 17th March 2016. WHO trial registration data set available at: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN64390461. TRIAL PROTOCOL VERSION: 12, 19th July 2018

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Digital endpoints in clinical trials: emerging themes from a multi-stakeholder Knowledge Exchange event

© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, to view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Background: Digital technologies, such as wearable devices and smartphone applications (apps), can enable the decentralisation of clinical trials by measuring endpoints in people’s chosen locations rather than in traditional clinical settings. Digital endpoints can allow high-frequency and sensitive measurements of health outcomes compared to visit-based endpoints which provide an episodic snapshot of a person’s health. However, there are underexplored challenges in this emerging space that require interdisciplinary and cross-sector collaboration. A multi-stakeholder Knowledge Exchange event was organised to facilitate conversations across silos within this research ecosystem. Methods: A survey was sent to an initial list of stakeholders to identify potential discussion topics. Additional stakeholders were identified through iterative discussions on perspectives that needed representation. Co-design meetings with attendees were held to discuss the scope, format and ethos of the event. The event itself featured a cross-disciplinary selection of talks, a panel discussion, small-group discussions facilitated via a rolling seating plan and audience participation via Slido. A transcript was generated from the day, which, together with the output from Slido, provided a record of the day’s discussions. Finally, meetings were held following the event to identify the key challenges for digital endpoints which emerged and reflections and recommendations for dissemination. Results: Several challenges for digital endpoints were identified in the following areas: patient adherence and acceptability; algorithms and software for devices; design, analysis and conduct of clinical trials with digital endpoints; the environmental impact of digital endpoints; and the need for ongoing ethical support. Learnings taken for next generation events include the need to include additional stakeholder perspectives, such as those of funders and regulators, and the need for additional resources and facilitation to allow patient and public contributors to engage meaningfully during the event. Conclusions: The event emphasised the importance of consortium building and highlighted the critical role that collaborative, multi-disciplinary, and cross-sector efforts play in driving innovation in research design and strategic partnership building moving forward. This necessitates enhanced recognition by funders to support multi-stakeholder projects with patient involvement, standardised terminology, and the utilisation of open-source software.Peer reviewe

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