BMP signalling regulates the pre-implantation development of extra-embryonic cell lineages in the mouse embryo.

Pre-implantation development requires the specification and organization of embryonic and extra-embryonic lineages. The separation of these lineages takes place when asymmetric divisions generate inside and outside cells that differ in polarity, position and fate. Here we assess the global transcriptional identities of these precursor cells to gain insight into the molecular mechanisms regulating lineage segregation. Unexpectedly, this reveals that complementary components of the bone morphogenetic protein (BMP) signalling pathway are already differentially expressed after the first wave of asymmetric divisions. We investigate the role of BMP signalling by expressing dominant negative forms of Smad4 and Bmpr2, by downregulating the pathway using RNA interference against BMP ligands and by applying three different BMP inhibitors at distinct stages. This reveals that BMP signalling regulates the correct development of both extra-embryonic lineages, primitive endoderm and trophectoderm, but not the embryonic lineage, before implantation. Together, these findings indicate multiple roles of BMP signalling in the early mouse embryo.This work was supported by a Wellcome Trust programme grant to MZG and an Agency for Science, Technology and Research (A*Star) core research budget to PR.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ncomms666

Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.We acknowledge the Wellcome Trust for supporting this work. H.B was supported by a Wellcome Trust clinical PhD fellowship. We acknowledge the Research Foundation Flanders (FWO) (FWO-G.A093.11 and FWO-G.0924.15 to T.V.; the travel grant V.4.140.10.N.00 to T.V.; N.V.d.A., E.F.G. and K.T. are Ph.D. students supported by FWO 1.1.H.28.12, FWO G.0924.15 and FWO 1126016N, respectively) and KU Leuven SymBioSys (PFV/10/016 to T.V.; P.K. is a PhD. student supported with PFV/10/016).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1116

Developing tools to promote culturally competent compassion, courage, and intercultural communication in healthcare

Background: Compassion is an important concept in healthcare, and in addition, care should be delivered in a culturally competent manner, taking into account the values, culture, and health beliefs of the individual. However, the training of nurses and other healthcare professionals may not adequately equip them to practice in a manner which is both compassionate and culturally competent. In this paper, we report on the development of three learning tools, designed to promote the skills and strengthen the capacity of nurses and healthcare professionals to provide culturally competent and compassionate care. Methods: The project involved the participation of six European countries in the development of three learning tools, covering culturally competent compassion, culturally competent courage, and intercultural communication. The principles which informed the methodology derive from the previous work on the Papadopoulos, Tilki and Taylor (PTT) model of transcultural nursing and cultural competence, and were also informed by the Intercultural Education of Nurses in Europe (IENE1 & IENE2) projects. Each partner country was required to produce one tool for each topic area, based on guidance provided by the project co-ordinator, leading to the development of eighteen tools in total. The tools were administered mainly to student nurses to test their feasibility. Results: The emerging tools contained important theoretical and practical components, whereby innovative learning methods and case studies were included. Student nurses enjoyed using the tools, and enjoyed their flexibility. The learning tools enabled students to become stimulated and to engage together leading to a positive learning experience. Discussion: The tools allow for a positive learning experience and reflection of good practice to take place. The flexibility and content of the tools allows for them to be of equal value to other healthcare professionals as well as nursing staff. Conclusion: The tools were initially utilised mainly with student nurses and were received with a positive response. Work is now in place to further implement the tools and evaluate the longer term effects among a range of healthcare professionals and service user health outcomes

Evidence of currents and unstable particle distributions in an extended region around the lunar plasma wake

We report observations of electrostatic ion acoustic waves and Langmuir waves during a recent lunar encounter by the Wind spacecraft. These waves are observed when Wind is magnetically connected to the nominal wake and at distances greater than 8 lunar radii from the wake. When interpreted in the context of a simple time‐of‐flight model, these observations imply the existence of a system of currents and disturbed particle distributions that extends far into solar wind

Comparison of breast and bowel cancer screening uptake patterns in a common cohort of South Asian women in England

Background: Inequalities in uptake of cancer screening by ethnic minority populations are well documented in a number of international studies. However, most studies to date have explored screening uptake for a single cancer only. This paper compares breast and bowel cancer screening uptake for a cohort of South Asian women invited to undertake both, and similarly investigates these women's breast cancer screening behaviour over a period of fifteen years. Methods: Screening data for rounds 1, 2 and 5 (1989-2004) of the NHS breast cancer screening programme and for round 1 of the NHS bowel screening pilot (2000-2002) were obtained for women aged 50-69 resident in the English bowel screening pilot site, Coventry and Warwickshire, who had been invited to undertake breast and bowel cancer screening in the period 2000-2002. Breast and bowel cancer screening uptake levels were calculated and compared using the chi-squared test. Results: 72,566 women were invited to breast and bowel cancer screening after exclusions. Of these, 3,539 were South Asian and 69,027 non-Asian; 18,730 had been invited to mammography over the previous fifteen years (rounds 1 to 5). South Asian women were significantly less likely to undertake both breast and bowel cancer screening; 29.9% (n = 1,057) compared to 59.4% (n = 40,969) for non-Asians (p < 0.001). Women in both groups who consistently chose to undertake breast cancer screening in rounds 1, 2 and 5 were more likely to complete round 1 bowel cancer screening. However, the likelihood of completion of bowel cancer screening was still significantly lower for South Asians; 49.5% vs. 82.3% for non-Asians, p < 0.001. South Asian women who undertook breast cancer screening in only one round were no more likely to complete bowel cancer screening than those who decided against breast cancer screening in all three rounds. In contrast, similar women in the non-Asian population had an increased likelihood of completing the new bowel cancer screening test. The likelihood of continued uptake of mammography after undertaking screening in round 1 differed between South Asian religio-linguistic groups. Noticeably, women in the Muslim population were less likely to continue to participate in mammography than those in other South Asian groups. Conclusions: Culturally appropriate targeted interventions are required to reduce observed disparities in cancer screening uptakes

Primary cilia elongation in response to interleukin-1 mediates the inflammatory response

Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50 % increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA

A questionnaire-based (UM-PDHQ) study of hallucinations in Parkinson's disease

Background: Hallucinations occur in 20-40% of PD patients and have been associated with unfavorable clinical outcomes (i.e., nursing home placement, increased mortality). Hallucinations, like other non-motor features of PD, are not well recognized in routine primary/secondary clinical practice. So far, there has been no instrument for uniform characterization of hallucinations in PD. To this end, we developed the University of Miami Parkinson's disease Hallucinations Questionnaire (UM-PDHQ) that allows comprehensive assessment of hallucinations in clinical or research settings.Methods: The UM-PDHQ is composed of 6 quantitative and 14 qualitative items. For our study PD patients of all ages and in all stages of the disease were recruited over an 18-month period. The UPDRS, MMSE, and Beck Depression and Anxiety Inventories were used for comparisons.Results and Discussion: Seventy consecutive PD patients were included in the analyses. Thirty-one (44.3%) were classified as hallucinators and 39 as non-hallucinators. No significant group differences were observed in terms of demographics, disease characteristics, stage, education, depressive/anxiety scores or cognitive functioning (MMSE) between hallucinators and non-hallucinators. Single mode hallucinations were reported in 20/31 (visual/14, auditory/4, olfactory/2) whereas multiple modalities were reported in 11/31 patients. The most common hallucinatory experience was a whole person followed by small animals, insects and reptiles.Conclusion: Using the UM-PDHQ, we were able to define the key characteristics of hallucinations in PD in our cohort. Future directions include the validation of the quantitative part of the questionnaire than will serve as a rating scale for severity of hallucinations

Theorizing compassion and empathy in educational contexts: what are compassion and empathy and why are they important?

The world is in constant change with growing inequality and access. When you watch the news, you are confronted with national disasters, wars/conflicts, waves of refugees and other crimes against humanity. At a national level, many countries have a changing political landscape that has seen a rise in fundamentalist nationalist parties leading to a discourse of 'problematic immigrants'. We also witness the decline of democratic ideals and the ethos of supporting people in society as politicians are influenced by capitalist ideals and individual gain. In essence, the world appears to be becoming meaner, with little understanding shown to others. When did values change

RNA-Seq Reveals an Integrated Immune Response in Nucleated Erythrocytes

Background: Throughout the primary literature and within textbooks, the erythrocyte has been tacitly accepted to have maintained a unique physiological role; namely gas transport and exchange. In non-mammalian vertebrates, nucleated erythrocytes are present in circulation throughout the life cycle and a fragmented series of observations in mammals support a potential role in non-respiratory biological processes. We hypothesised that nucleated erythrocytes could actively participate via ligand-induced transcriptional re-programming in the immune response. Methodology/Principal Findings: Nucleated erythrocytes from both fish and birds express and regulate specific pattern recognition receptor (PRR) mRNAs and, thus, are capable of specific pathogen associated molecular pattern (PAMP) detection that is central to the innate immune response. In vitro challenge with diverse PAMPs led to de novo specific mRNA synthesis of both receptors and response factors including interferon-alpha (IFNα) that exhibit a stimulus-specific polysomal shift supporting active translation. RNA-Seq analysis of the PAMP (Poly (I:C), polyinosinic:polycytidylic acid)-erythrocyte response uncovered diverse cohorts of differentially expressed mRNA transcripts related to multiple physiological systems including the endocrine, reproductive and immune. Moreover, erythrocyte-derived conditioned mediums induced a type-1 interferon response in macrophages thus supporting an integrative role for the erythrocytes in the immune response. Conclusions/Significance: We demonstrate that nucleated erythrocytes in non-mammalian vertebrates spanning significant phylogenetic distance participate in the immune response. RNA-Seq studies highlight a mRNA repertoire that suggests a previously unrecognized integrative role for the erythrocytes in other physiological systems

Ion-scale Electromagnetic Waves in the Inner Heliosphere

International audienceUnderstanding the physical processes in the solar wind and corona that actively contribute to heating, acceleration, and dissipation is a primary objective of NASA's Parker Solar Probe (PSP) mission. Observations of circularly polarized electromagnetic waves at ion scales suggest that cyclotron resonance and wave-particle interactions are dynamically relevant in the inner heliosphere. A wavelet-based statistical study of circularly polarized events in the first perihelion encounter of PSP demonstrates that transverse electromagnetic waves at ion resonant scales are observed in 30-50% of radial field intervals. Average wave amplitudes of approximately 4 nT are measured, while the mean duration of wave events is on the order of 20 s; however, long-duration wave events can exist without interruption on hour-long timescales. Determination of wave vectors suggests propagation parallel/antiparallel to the mean magnetic field. Though ion-scale waves are preferentially observed during intervals with a radial mean magnetic field, we show that measurement constraints, associated with single spacecraft sampling of quasi-parallel waves superposed with anisotropic turbulence, render the measured coherent ion-wave spectrum unobservable when the mean magnetic field is oblique to the solar wind flow; these results imply that the occurrence of coherent ion-scale waves is not limited to a radial field configuration. The lack of radial scaling of characteristic wave amplitudes and duration suggests that the waves are generated in situ through plasma instabilities. Additionally, observations of proton distribution functions indicate that temperature anisotropy may drive the observed ion-scale