Comprehensive methylome map of lineage commitment from haematopoietic progenitors.

Epigenetic modifications must underlie lineage-specific differentiation as terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Haematopoiesis provides a well-defined model to study epigenetic modifications during cell-fate decisions, as multipotent progenitors (MPPs) differentiate into progressively restricted myeloid or lymphoid progenitors. Although DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs, a comprehensive DNA methylation map of haematopoietic progenitors, or of any multipotent/oligopotent lineage, does not exist. Here we examined 4.6 million CpG sites throughout the genome for MPPs, common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Marked epigenetic plasticity accompanied both lymphoid and myeloid restriction. Myeloid commitment involved less global DNA methylation than lymphoid commitment, supported functionally by myeloid skewing of progenitors following treatment with a DNA methyltransferase inhibitor. Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands. Many examples of genes and pathways not previously known to be involved in choice between lymphoid/myeloid differentiation have been identified, such as Arl4c and Jdp2. Several transcription factors, including Meis1, were methylated and silenced during differentiation, indicating a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome seems to be important in haematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation and defines a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions

Determinants of timeliness in early childhood vaccination among mothers with vaccination cards in Sindh province, Pakistan:a secondary analysis of cross-sectional survey data

OBJECTIVE: Untimely vaccination refers to receiving the given dose before (early) or after (delayed) the recommended time window. The purpose of this study was to assess the extent of timeliness of childhood vaccinations and examine the determinants of vaccination timeliness in Sindh province, Pakistan. DESIGN: Cross-sectional analysis of data from the 2013 and 2014 Maternal and Child Health Program Indicator Surveys. SETTING: Community-based maternal and child health surveys. PARTICIPANTS: Among 10 200 respondents of Maternal and Child Health Program Indicator Surveys, 1143 women who had a live birth in the 2 years preceding the survey were included. OUTCOMES: At the participants' home, an interviewer asked mothers to show their children's vaccination cards, which contained information regarding vaccinations. Children's vaccination status was categorised into timely or early/delayed compared with vaccination schedule. A logistic regression analysis using Firth's penalised likelihood was performed to identify factors associated with timeliness of vaccinations. RESULTS: 238 children (20.8% of children who received a full set of basic vaccinations) received all vaccinations on schedule among children who received a full set of basic vaccinations. The percentages of timely vaccinations ranged from 2.3% for second measles vaccination to 89.3% for bacillus Calmette-Guérin. Child's age and place of delivery were associated with timely vaccinations. Older child age and institutional delivery were associated with decreased timely vaccination rate. CONCLUSIONS: Home-based vaccination record is a key tool to improve the timeliness of vaccinations. The redesigned vaccination cards, the new electronic registries for vaccination card information and the vaccination tracking system to remind the second/third vaccination visits may be helpful to improve timely vaccinations for children under 2 years old

Narrativity and Literariness Affect the Aesthetic Attitude in Text Reading

We report two pre-registered experiments investigating some of the conditions under which readers focus on aesthetically relevant object properties in text processing. Experiment 1 (N=159) tested the role of narrativity, psychological information about textual characters, and readers’ identification with them. Participants’ focus on aesthetically relevant object properties was stronger after reading a narrative than an expository text. This relationship between participants’ focus and narrativity was not affected by information about textual characters, or readers’ identification with them. Experiment 2 (N=159) tested the role of narrativity, literariness, and readers’ perception of literary features. Again, reading a narrative led to a stronger focus on aesthetically relevant object properties than reading an expository text. The effect of literary narratives was meditated by readers’ perception of literary features. In sum, narrativity and literariness, but not information about characters or identification with them affect the degree to which readers focus on aesthetically relevant object properties

Is There Such a Thing as a Biosignature?

The concept of a biosignature is widely used in astrobiology to suggest a link between some observation and a biological cause, given some context. The term itself has been defined and used in several ways in different parts of the scientific community involved in the search for past or present life on Earth and beyond. With the ongoing acceleration in the search for life in distant time and/or deep space, there is a need for clarity and accuracy in the formulation and reporting of claims. Here, we critically review the biosignature concept(s) and the associated nomenclature in light of several problems and ambiguities emphasized by recent works. One worry is that these terms and concepts may imply greater certainty than is usually justified by a rational interpretation of the data. A related worry is that terms such as “biosignature” may be inherently misleading, for example, because the divide between life and non-life—and their observable effects—is fuzzy. Another worry is that different parts of the multidisciplinary community may use non-equivalent or conflicting definitions and conceptions, leading to avoidable confusion. This review leads us to identify a number of pitfalls and to suggest how they can be circumvented. In general, we conclude that astrobiologists should exercise particular caution in deciding whether and how to use the concept of biosignature when thinking and communicating about habitability or life. Concepts and terms should be selected carefully and defined explicitly where appropriate. This would improve clarity and accuracy in the formulation of claims and subsequent technical and public communication about some of the most profound and important questions in science and society. With this objective in mind, we provide a checklist of questions that scientists and other interested parties should ask when assessing any reported detection of a “biosignature” to better understand exactly what is being claimed

Reconstructing EUV spectrum of star forming regions from millimeter recombination lines of HI, HeI, and HeII

The extreme ultraviolet (EUV) spectra of distant star-forming regions cannot be probed directly using either ground- or space-based telescopes due to the high cross-section for interaction of EUV photons with the interstellar medium. This makes EUV spectra poorly constrained. The mm/submm recombination lines of H and He, which can be observed from the ground, can serve as a reliable probe of the EUV. Here we present a study based on ALMA observations of three Galactic ultra-compact HII regions and the starburst region Sgr B2(M), in which we reconstruct the key parameters of the EUV spectra using mm recombination lines of HI, HeI and HeII. We find that in all cases the EUV spectra between 13.6 and 54.4 eV have similar frequency dependence: L_{\nu}~ \nu^{-4.5 +/- 0.4}. We compare the inferred values of the EUV spectral slopes with the values expected for a purely single stellar evolution model (Starburst99) and the Binary Population and Spectral Synthesis code (BPASS). We find that the observed spectral slope differs from the model predictions. This may imply that the fraction of interacting binaries in HII regions is substantially lower than assumed in BPASS. The technique demonstrated here allows one to deduce the EUV spectra of star forming regions providing critical insight into photon production rates at \lambda < 912 A and can serve as calibration to starburst synthesis models, improving our understanding of star formation in distant universe and the properties of ionizing flux during reionization.Comment: v1: 18 pages, 5 figures, 1 table, 1 appendix v2: BPASS version 2.1 -> 2.2.1, SB99 tracks explicitly added to figures, evolution with metallicity added, few points clarified. 20 pages, 6 figures, 1 table. Accepted to Ap

Reconstructing the EUV Spectrum of Star-forming Regions from Millimeter Recombination Lines of H I, He I, and He II

The extreme ultraviolet (EUV) spectra of distant star-forming regions cannot be probed directly using either ground- or space-based telescopes due to the high cross section for interaction of EUV photons with the interstellar medium. This makes EUV spectra poorly constrained. The millimeter/submillimeter recombination lines of H and He, which can be observed from the ground, can serve as a reliable probe of the EUV. Here we present a study based on ALMA observations of three Galactic ultracompact H II regions and the starburst region Sgr B2(M), in which we reconstruct the key parameters of the EUV spectra using millimeter recombination lines of H I, He I, and He II. We find that in all cases the EUV spectra between 13.6 and 54.4 eV have similar frequency dependence: L_ ν ∝ ν^(-4.5±0.4). We compare the inferred values of the EUV spectral slopes with the values expected for a purely single stellar evolution model (Starburst99) and the Binary Population and Spectral Synthesis code (BPASS). We find that the observed spectral slope differs from the model predictions. This may imply that the fraction of interacting binaries in H II regions is substantially lower than assumed in BPASS. The technique demonstrated here allows one to deduce the EUV spectra of star-forming regions, providing critical insight into photon production rates at λ ⩽ 912 Å, and can serve as calibration to starburst synthesis models, improving our understanding of star formation in the distant universe and the properties of ionizing flux during reionization

Interacting with eHealth - Towards grand challenges for HCI

While health records are increasingly stored electronically, we, as citizens, have little access to this data about ourselves. We are not used to thinking of these official records either as ours or as useful to us. We increasingly turn to the Web, however, to query any ache, pain or health goal we may have before consulting with health care professionals. Likewise, for proactive health care such as nutrition or fitness, or to find fellow-sufferers for post diagnosis support, we turn to online resources. There is a potential disconnect between points at which professional and lay eHealth data and resources intersect for preventative or proactive health care. Such gaps in information sharing may have direct impact on practices we decide to take up, the care we seek, or the support professionals offer. In this panel, we consider several places within proactive, preventative health care in particular HCI has a role towards enhancing health knowledge discovery and health support interaction. Our goal is to demonstrate how now is the time for eHealth to come to the forefront of the HCI research agenda

Homeostatic interferon-lambda response to bacterial microbiota stimulates preemptive antiviral defense within discrete pockets of intestinal epithelium

Interferon-lambda (IFN-λ) protects intestinal epithelial cells (IECs) from enteric viruses by inducing expression of antiviral IFN-stimulated genes (ISGs). Here, we find that bacterial microbiota stimulate a homeostatic ISG signature in the intestine of specific pathogen-free mice. This homeostatic ISG expression is restricted to IECs, depends on IEC-intrinsic expression of IFN-λ receptor

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling