Reconstruction of the repetitive antifreeze glycoprotein genomic loci in the cold-water gadids Boreogadus saida and Microgadus tomcod.

Abstract Antifreeze glycoproteins (AFGPs) are a novel evolutionary innovation in members of the northern cod fish family (Gadidae), crucial in preventing death from inoculative freezing by environmental ice in their frigid Arctic and sub-Arctic habitats. However, the genomic origin and molecular mechanism of evolution of this novel life-saving adaptive genetic trait remained to be definitively determined. To this end, we constructed large insert genomic DNA BAC (bacterial artificial chromosome) libraries for two AFGP-bearing gadids, the high-Arctic polar cod Boreogadus saida and the cold-temperate Atlantic tomcod Microgadus tomcod, to isolate and sequence their AFGP genomic regions for fine resolution evolutionary analyses. The BAC library construction encountered poor cloning efficiency initially, which we resolved by pretreating the agarose-embedded erythrocyte DNA with a cationic detergent, a method that may be of general use to BAC cloning for teleost species and/or where erythrocytes are the source of input DNA. The polar cod BAC library encompassed 92,160 clones with an average insert size of 94.7 kbp, and the Atlantic tomcod library contained 73,728 clones with an average insert size of 89.6 kbp. The genome sizes of B. saida and M. tomcod were estimated by cell flow cytometry to be 836 Mbp and 645 Mbp respectively, thus their BAC libraries have approximately 10- and 9.7-fold genome coverage respectively. The inclusiveness and depth of coverage were empirically confirmed by screening the libraries with three housekeeping genes. The BAC clones that mapped to the AFGP genomic loci of the two gadids were then isolated by screening the BAC libraries with gadid AFGP gene probes. Eight minimal tiling path (MTP) clones were identified for B. saida, sequenced, and assembled. The B. saida AFGP locus reconstruction produced both haplotypes, and the locus comprises three distinct AFGP gene clusters, containing a total of 16 AFGP genes and spanning a combined distance of 512 kbp. The M. tomcod AFGP locus is much smaller at approximately 80 kbp, and contains only three AFGP genes. Fluorescent in situ hybridization with an AFGP gene probe showed the AFGP locus in both species occupies a single chromosomal location. The large AFGP locus with its high gene dosage in B. saida is consistent with its chronically freezing high Arctic habitats, while the small gene family in M. tomcod correlates with its milder habitats in lower latitudes. The results from this study provided the data for fine resolution sequence analyses that would yield insight into the molecular mechanisms and history of gadid AFGP gene evolution driven by northern hemisphere glaciation

Health literacy development is central to the prevention and control of non-communicable diseases

Funding Information: This study was funded in part by National Health and Medical Research Council (Principal Research Fellowship APP1155125). Publisher Copyright: © 2022 Author(s). Published by BMJ.The WHO's report Health literacy development for the prevention and control of non-communicable diseases (NCDs) delivers practical what-to-do how-to-do guidance for health literacy development to build, at scale, contextually-relevant public health actions to reduce inequity and the burden of NCDs on individuals, health systems and economies. The key premise for health literacy development is that people's health awareness and behaviours are linked to lifelong experiences and social practices, which may be multilayered, hidden and beyond their control. Meaningful community engagement, local ownership and locally driven actions are needed to identify health literacy strengths, challenges and preferences to build locally fit-for-purpose and implementable actions. Health literacy development needs to underpin local and national policy, laws and regulations to create enabling environments that reduce community exposures to NCD risk factors. Deficit approaches and siloed health system and policy responses need to be avoided, focusing instead on integrating community-based solutions through co-design, cognisant of people's daily experiences and social practices.publishersversionpublishe

A V-Band Survey for Variable Galactic Nuclei in the Hubble Deep Field

We present the results of a 2-epoch variability survey in the Hubble Deep Field with the goal of investigating the population of AGN to z=1. The primary data sets analyzed for galactic variability are the original HDF observations obtained in 1995 and a second V-band image obtained 5 years later in 2000. We find evidence for nuclear variability in 16 of 217 galaxies brighter than V_nuc=27.5. Correcting for incompleteness and spurious detections, variable nuclei make up ~8% of the surveyed galaxies. Seven of our variable sources are coincident with X-ray sources detected in the 2Ms Chandra survey. We find that 44% of the variable nuclei are associated with mid-IR detections at 15 microns and 31% are detected at 1.4GHz. Optical spectra are available for 13 of the 16 variables. One is a broad-line AGN and 2 others show weak evidence of type 2 AGNs. With the assumption that these variables are all active nuclei, we estimate the AGN LF at 0.4<z<1.1 extending to M_B=-15. We find evidence for an increase in the number density of faint AGN when comparing to the local Seyfert luminosity function. The LF for optically varying nuclei appears to rise in number density with no evidence of turning over at these faint magnitudes.Comment: 33 pages, 9 figures, to be published in Dec. 2003 Ap

First Measurement of Monoenergetic Muon Neutrino Charged Current Interactions

We report the first measurement of monoenergetic muon neutrino charged current interactions. MiniBooNE has isolated 236 MeV muon neutrino events originating from charged kaon decay at rest ($K^+ \rightarrow \mu^+ \nu_\mu$) at the NuMI beamline absorber. These signal $\nu_\mu$-carbon events are distinguished from primarily pion decay in flight $\nu_\mu$ and $\overline{\nu}_\mu$ backgrounds produced at the target station and decay pipe using their arrival time and reconstructed muon energy. The significance of the signal observation is at the 3.9$\sigma$ level. The muon kinetic energy, neutrino-nucleus energy transfer ($\omega=E_\nu-E_\mu$), and total cross section for these events is extracted. This result is the first known-energy, weak-interaction-only probe of the nucleus to yield a measurement of $\omega$ using neutrinos, a quantity thus far only accessible through electron scattering.Comment: 6 pages, 4 figure

Nationwide Genomic Study in Denmark Reveals Remarkable Population Homogeneity

Denmark has played a substantial role in the history of Northern Europe. Through a nationwide scientific outreach initiative, we collected genetic and anthropometrical data from ∼800 high school students and used them to elucidate the genetic makeup of the Danish population, as well as to assess polygenic predictions of phenotypic traits in adolescents. We observed remarkable homogeneity across different geographic regions, although we could still detect weak signals of genetic structure reflecting the history of the country. Denmark presented genomic affinity with primarily neighboring countries with overall resemblance of decreasing weight from Britain, Sweden, Norway, Germany, and France. A Polish admixture signal was detected in Zealand and Funen, and our date estimates coincided with historical evidence of Wend settlements in the south of Denmark. We also observed considerably diverse demographic histories among Scandinavian countries, with Denmark having the smallest current effective population size compared to Norway and Sweden. Finally, we found that polygenic prediction of self-reported adolescent height in the population was remarkably accurate (R2 = 0.639 ± 0.015). The high homogeneity of the Danish population could render population structure a lesser concern for the upcoming large-scale gene-mapping studies in the country

Pharmacological Inhibition of Epac1 Averts Ferroptosis Cell Death by Preserving Mitochondrial Integrity

Exchange proteins directly activated by cAMP (Epac) proteins are implicated in a wide range of cellular functions including oxidative stress and cell survival. Mitochondrial-dependent oxidative stress has been associated with progressive neuronal death underlying the pathology of many neurodegenerative diseases. The role of Epac modulation in neuronal cells in relation to cell survival and death, as well as its potential effect on mitochondrial function, is not well established. In immortalized hippocampal (HT-22) neuronal cells, we examined mitochondria function in the presence of various Epac pharmacological modulators in response to oxidative stress due to ferroptosis. Our study revealed that selective pharmacological modulation of Epac1 or Epac2 isoforms, exerted differential effects in erastin-induced ferroptosis conditions in HT-22 cells. Epac1 inhibition prevented cell death and loss of mitochondrial integrity induced by ferroptosis, while Epac2 inhibition had limited effects. Our data suggest Epac1 as a plausible therapeutic target for preventing ferroptosis cell death associated with neurodegenerative diseases

embracing diversity in a strengths-based approach to promote health and equity, and avoid epistemic injustice

APP1155125. Publisher Copyright: © 2022 Author(s) (or their employer(s)).Definitions of health literacy have evolved from notions of health-related literacy to a multidimensional concept that incorporates the importance of social and cultural knowledge, practices and contexts. This evolution is evident in the development of instruments that seek to measure health literacy in different ways. Health literacy measurement is important for global health because diverse stakeholders, including the WHO, use these data to inform health practice and policy, and to understand sources of inequity. In this Practice paper, we explore the potential for negative consequences, bias and epistemic injustice to occur when health literacy instruments are used across settings without due regard for the lived experiences of people in various contexts from whom data are collected. A health literacy measurement approach that is emic-sensitive, strengths based and solution oriented is needed to minimise biased data interpretation and use and to avoid epistemic injustice.publishersversionpublishe

Left atrial giant thrombus infected by Escherichia Coli. Case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens