Interactive effects of inbreeding and endocrine disruption on reproduction in a model laboratory fish

This is the final version of the article. Available from Wiley via the DOI in this record.Inbreeding depression is expected to be more severe in stressful environments. However, the extent to which inbreeding affects the vulnerability of populations to environmental stressors, such as chemical exposure, remains unresolved. Here we report on the combined impacts of inbreeding and exposure to an endocrine disrupting chemical (the fungicide clotrimazole) on zebrafish (Danio rerio). We show that whilst inbreeding can negatively affect reproductive traits, not all traits are affected equally. Inbreeding depression frequently only became apparent when fish were additionally stressed by chemical exposure. Embryo viability was significantly reduced in inbred exposed fish and there was a tendency for inbred males to sire fewer offspring when in direct competition with outbred individuals. Levels of plasma 11-ketotestosterone, a key male sex hormone, showed substantial inbreeding depression that was unaffected by addition of the fungicide. In contrast, there was no effect of inbreeding or clotrimazole exposure on egg production. Overall, our data provide evidence that stress may amplify the effects of inbreeding on key reproductive traits, particularly those associated with male fitness. This may have important implications when considering the consequences of exposure to chemical pollutants on the fitness of wild populations.Thanks to NERC's Post Genomics & Proteomics Programme NE/F0077871/1 and AstraZeneca's Safety, Health and Environment Research Programme for funding this work. We thank Alexander Scott (11-ketotestosterone radioimmunoassay) at the Centre for Environment, Fisheries and Aquaculture Science, Jan Shears and Luanne Wilkes at University of Exeter, Gareth Readman, Vicki Cammack, Kate Hurd and Yohanna Glennon at Brixham Environmental Laboratory for their assistance

TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse

Genome‐wide recombination is essential for genome stability, evolution, and speciation. Mouse Tex11, an X‐linked meiosis‐specific gene, promotes meiotic recombination and chromosomal synapsis. Here, we report that TEX11 is mutated in infertile men with non‐obstructive azoospermia and that an analogous mutation in the mouse impairs meiosis. Genetic screening of a large cohort of idiopathic infertile men reveals that TEX11 mutations, including frameshift and splicing acceptor site mutations, cause infertility in 1% of azoospermic men. Functional evaluation of three analogous human TEX11 missense mutations in transgenic mouse models identified one mutation (V748A) as a potential infertility allele and found two mutations non‐causative. In the mouse model, an intronless autosomal Tex11 transgene functionally substitutes for the X‐linked Tex11 gene, providing genetic evidence for the X‐to‐autosomal retrotransposition evolution phenomenon. Furthermore, we find that TEX11 protein levels modulate genome‐wide recombination rates in both sexes. These studies indicate that TEX11 alleles affecting expression level or substituting single amino acids may contribute to variations in recombination rates between sexes and among individuals in humans.Howard Hughes Medical Institute (Award)National Institutes of Health (U.S.) (NIH/NIGMS grant R01GM076327

The Drosophila Zinc Finger Protein Trade Embargo Is Required for Double Strand Break Formation in Meiosis

Homologous recombination in meiosis is initiated by the programmed induction of double strand breaks (DSBs). Although the Drosophila Spo11 ortholog Mei-W68 is required for the induction of DSBs during meiotic prophase, only one other protein (Mei-P22) has been shown to be required for Mei-W68 to exert this function. We show here that the chromatin-associated protein Trade Embargo (Trem), a C2H2 zinc finger protein, is required to localize Mei-P22 to discrete foci on meiotic chromosomes, and thus to promote the formation of DSBs, making Trem the earliest known function in the process of DSB formation in Drosophila oocytes. We speculate that Trem may act by either directing the binding of Mei-P22 to preferred sites of DSB formation or by altering chromatin structure in a manner that allows Mei-P22 to form foci

corona Is Required for Higher-Order Assembly of Transverse Filaments into Full-Length Synaptonemal Complex in Drosophila Oocytes

The synaptonemal complex (SC) is an intricate structure that forms between homologous chromosomes early during the meiotic prophase, where it mediates homolog pairing interactions and promotes the formation of genetic exchanges. In Drosophila melanogaster, C(3)G protein forms the transverse filaments (TFs) of the SC. The N termini of C(3)G homodimers localize to the Central Element (CE) of the SC, while the C-termini of C(3)G connect the TFs to the chromosomes via associations with the axial elements/lateral elements (AEs/LEs) of the SC. Here, we show that the Drosophila protein Corona (CONA) co-localizes with C(3)G in a mutually dependent fashion and is required for the polymerization of C(3)G into mature thread-like structures, in the context both of paired homologous chromosomes and of C(3)G polycomplexes that lack AEs/LEs. Although AEs assemble in cona oocytes, they exhibit defects that are characteristic of c(3)G mutant oocytes, including failure of AE alignment and synapsis. These results demonstrate that CONA, which does not contain a coiled coil domain, is required for the stable ‘zippering’ of TFs to form the central region of the Drosophila SC. We speculate that CONA's role in SC formation may be similar to that of the mammalian CE proteins SYCE2 and TEX12. However, the observation that AE alignment and pairing occurs in Tex12 and Syce2 mutant meiocytes but not in cona oocytes suggests that the SC plays a more critical role in the stable association of homologs in Drosophila than it does in mammalian cells

Do you see what I see? Identification of child protection concerns by hospital staff and general dental practitioners

Aim An exploration of the threshold that dentists, doctors and nurses recognise for dental and child protection (CP) actions in sample clinical cases, and any differences between these professional groups. Method We present a cross-sectional survey of dentists, doctors and nurses (50 each), who regularly examine children, utilised five fictitious vignettes, combining an oral examination image and clinical history reflecting dental and CP issues. Demographics were collected, and each participant gave their likely action for the cases presented. Results Dentists were significantly better at answering the dental element than the doctors and nurses, (P <0.0001) with no significant difference between these two; only 8% of the latter had undergone any training in assessment of dental health. Although 90.6% of all professionals had undergone CP training, dentists were significantly less accurate at identifying the CP component than doctors and nurses, (P <0.0001) between whom there were no significant differences. Those with higher levels of CP training were most accurate at identifying correct CP actions. Conclusions CP training is effective at improving recognition of child maltreatment, although there remains a worrying lack of knowledge about thresholds for action among dentists. Doctors and nurses have minimal training in, or knowledge of, dental health in children, thus precluding appropriate onward referrals

A novel low-cost, high-resolution camera system for measuring peat subsidence and water table dynamics

This is the final version. Available from Frontiers Media via the DOI in this record. DATA AVAILABILITY STATEMENT: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Peatlands are highly dynamic systems, able to accumulate carbon over millennia under natural conditions, but susceptible to rapid subsidence and carbon loss when drained. Short-term, seasonal and long-term peat surface elevation changes are closely linked to key peatland attributes such as water table depth (WTD) and carbon balance, and may be measured remotely using satellite radar and LiDAR methods. However, field measurements of peat elevation change are spatially and temporally sparse, reliant on low-resolution manual subsidence pole measurements, or expensive sensor systems. Here we describe a novel, simple and low-cost image-based method for measuring peat surface motion and WTD using commercially available time-lapse cameras and image processing methods. Based on almost two years’ deployment of peat cameras across contrasting forested, burned, agricultural and oil palm plantation sites in Central Kalimantan, Indonesia, we show that the method can capture extremely high resolution (sub-mm) and high-frequency (sub-daily) changes in peat surface elevation over extended periods and under challenging environmental conditions. WTD measurements were of similar quality to commercially available pressure transducers. Results reveal dynamic peat elevation response to individual rain events, consistent with variations in WTD. Over the course of the relatively severe 2019 dry season, cameras in deep-drained peatlands recorded maximum peat shrinkage of over 8 cm, followed by partial rebound, leading to net annual subsidence of up to 5 cm. Sites with higher water tables, and where borehole irrigation was used to maintain soil moisture, had lower subsidence, suggesting potential to reduce subsidence through altered land-management. Given the established link between subsidence and CO2 emissions, these results have direct implications for the management of peatlands to reduce high current greenhouse gas (GHG) emissions. Camera-based sensors provide a simple, low-cost alternative to commercial elevation, WTD and GHG flux monitoring systems, suitable for deployment at scale, and in areas where existing approaches are impractical or unaffordable. If ground-based observations of peat motion can be linked to measured GHG fluxes and with satellite-based monitoring tools, this approach offers the potential for a large-scale peatland monitoring tool, suitable for identifying areas of active carbon loss, targeting climate change mitigation interventions, and evaluating intervention outcomes.United Kingdom Space Agency International Partnership ProgramBiotechnology and Biological Sciences Research CouncilNatural Environment Research CouncilNatural Environment Research Counci

The Meiotic Recombination Checkpoint Suppresses NHK-1 Kinase to Prevent Reorganisation of the Oocyte Nucleus in Drosophila

The meiotic recombination checkpoint is a signalling pathway that blocks meiotic progression when the repair of DNA breaks formed during recombination is delayed. In comparison to the signalling pathway itself, however, the molecular targets of the checkpoint that control meiotic progression are not well understood in metazoans. In Drosophila, activation of the meiotic checkpoint is known to prevent formation of the karyosome, a meiosis-specific organisation of chromosomes, but the molecular pathway by which this occurs remains to be identified. Here we show that the conserved kinase NHK-1 (Drosophila Vrk-1) is a crucial meiotic regulator controlled by the meiotic checkpoint. An nhk-1 mutation, whilst resulting in karyosome defects, does so independent of meiotic checkpoint activation. Rather, we find unrepaired DNA breaks formed during recombination suppress NHK-1 activity (inferred from the phosphorylation level of one of its substrates) through the meiotic checkpoint. Additionally DNA breaks induced by X-rays in cultured cells also suppress NHK-1 kinase activity. Unrepaired DNA breaks in oocytes also delay other NHK-1 dependent nuclear events, such as synaptonemal complex disassembly and condensin loading onto chromosomes. Therefore we propose that NHK-1 is a crucial regulator of meiosis and that the meiotic checkpoint suppresses NHK-1 activity to prevent oocyte nuclear reorganisation until DNA breaks are repaired

Consensus Paper—ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia

The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients—the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit