In Vitro Interactions of Extracellular Histones with LDL Suggest a Potential Pro-Atherogenic Role

BACKGROUND: Nuclear histones have previously been shown to aggregate LDL in vitro, suggestive of a possible pro-atherogenic role. Recent studies indicate that histones are released during acute inflammation, and therefore might interact with circulating lipoproteins in vivo. In view of the associative link between inflammation and cardiovascular disease, the behaviour of histones was investigated using in vitro models of LDL retention and foam cell formation. METHODOLOGY/PRINCIPAL FINDINGS: Heparin agarose beads were used as a model of a matrix rich in sulphated glycosaminoglycans, to which histones bind strongly. Histone-modified beads were observed to pull down more LDL from solution than untreated beads, indicating that histones can function as bridging molecules, enhancing LDL retention. Furthermore, addition of heparin inhibited histone-induced aggregation of LDL. To model foam cell formation, murine RAW 264.7 macrophages were incubated for 24 h in the presence of LDL, histones, LDL plus histones or vehicle control. Cells incubated with LDL in the presence of histones accumulated significantly more intracellular lipid than with LDL or histone alone. CONCLUSIONS/SIGNIFICANCE: These results are consistent with a potential pro-atherogenic role for extracellular histones, which should be investigated further

Nonadaptive evolution of mitochondrial genome size

Genomes vary greatly in size and complexity, and identifying the evolutionary forces that have generated this variation remains a major goal in biology. A controversial proposal is that most changes in genome size are initially deleterious and therefore are linked to episodes of decrease in effective population sizes. Support for this hypothesis comes from large-scale comparative analyses, but vanishes when phylogenetic nonindependence is taken into account. Another approach to test this hypothesis involves analyzing sequence evolution among clades where duplications have recently fixed. Here we show that episodes of fixation of duplications in mitochondrial genomes of the gecko Heteronotia binoei (two independent clades) and of mantellid frogs (five distinct branches) coincide with reductions in the ability of selection to purge slightly deleterious mutations. Our results support the idea that genome complexity can arise through nonadaptive processes in tetrapods. © 2011 The Author(s). Evolution © 2011 The Society for the Study of Evolution

Evaluation of ADAM-12 as a diagnostic biomarker of ectopic pregnancy in women with a pregnancy of unknown location

Ectopic pregnancy (EP) remains the most life-threatening acute condition in modern gynaecology. It remains difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a 'pregnancy of unknown location' (PUL) and diagnosis/exclusion of EP is challenging due to a lack of reliable biomarkers. Recent studies suggest that serum levels of a disintegrin and metalloprotease protein-12 (ADAM-12) can be used differentiate EP from viable intrauterine pregnancy (VIUP). Here we describe a prospective study evaluating the performance of ADAM-12 in differentiating EP from the full spectrum of alternative PUL outcomes in an independent patient cohort.Sera were collected from 120 patients at their first clinical presentation with a PUL and assayed for ADAM-12 by ELISA. Patients were categorized according to final pregnancy outcomes. Serum ADAM-12 concentrations were increased in women with histologically-confirmed EP (median 442 pg/mL; 25%-75% percentile 232-783 pg/mL) compared to women with VIUP (256 pg/mL; 168-442 pg/mL) or miscarriage (192 pg/mL; 133-476 pg/mL). Serum ADAM-12 did not differentiate histologically-confirmed EP from spontaneously resolving PUL (srPUL) (416 pg/mL; 154-608 pg/mL). The diagnostic potential of ADAM-12 was only significant when 'ambiguous' PUL outcomes were excluded from the analysis (AROC = 0.6633; P = 0.03901).When measured in isolation, ADAM-12 levels had limited value as a diagnostic biomarker for EP in our patient cohort. The development of a reliable serum biomarker-based test for EP remains an ongoing challenge

Panchromatic Imaging of a Transitional Disk: The Disk of GM Aur in Optical and FUV Scattered Light

We have imaged GM Aur with HST, detected its disk in scattered light at 1400A and 1650A, and compared these with observations at 3300A, 5550A, 1.1 microns, and 1.6 microns. The scattered light increases at shorter wavelengths. The radial surface brightness profile at 3300A shows no evidence of the 24AU radius cavity that has been previously observed in sub-mm observations. Comparison with dust grain opacity models indicates the surface of the entire disk is populated with sub-micron grains. We have compiled an SED from 0.1 microns to 1 mm, and used it to constrain a model of the star+disk system that includes the sub-mm cavity using the Monte Carlo Radiative Transfer code by Barbara Whitney. The best-fit model image indicates that the cavity should be detectable in the F330W bandpass if the cavity has been cleared of both large and small dust grains, but we do not detect it. The lack of an observed cavity can be explained by the presence of sub-microns grains interior to the sub-mm cavity wall. We suggest one explanation for this which could be due to a planet of mass <9 Jupiter masses interior to 24 AU. A unique cylindrical structure is detected in the FUV data from the Advanced Camera for Surveys/Solar Blind Channel. It is aligned along the system semi-minor axis, but does not resemble an accretion-driven jet. The structure is limb-brightened and extends 190 +/- 35 AU above the disk midplane. The inner radius of the limb-brightening is 40 +/- 10 AU, just beyond the sub-millimeter cavity wall.Comment: 40 pages, 11 figures, 4 tables, accepted to Ap

Gene Expression Pattern Analysis of Anterior Hox Genes during Zebrafish (Danio rerio) Embryonic Development Reveals Divergent Expression Patterns from Other Teleosts

The regional identity of organs and organ systems along the anterior-posterior axis during embryonic development is patterned, in part, by Hox genes, which encode transcription factor proteins that activate or repress the expression of downstream target genes. Divergent nested Hox gene expression patterns may have had a role in facilitating morphological divergence of structures, such as the pharyngeal jaw apparatus, among evolutionarily divergent teleost fishes. Recent studies from several evolutionarily divergent teleosts, such as the Japanese Medaka (Oryzias latipes) and the Nile Tilapia (Oreochromis niloticus), have shown the presence of divergent expression patterns of several Hox genes within paralog groups 2–5 between these species. Specifically, these expression patterns were documented in the pharyngeal arches, which give rise to the pharyngeal jaw apparatus. While the expression patterns of several Zebrafish (Danio rerio) Hox genes that are orthologous to those of Medaka and Tilapia have been documented within the developing hindbrain and pharyngeal arches, many still have yet to be documented, especially within the pharyngeal arches during the postmigratory cranial neural crest cell stages. Here, we present the expression patterns of six Zebrafish Hox genes, hoxc3a, d3a, a4a, d4a, b5a, and c5a, within the pharyngeal arches during a postmigratory cranial neural crest cell stage and compare them to their orthologous genes of Medaka and Tilapia at similar stages. We show that while hoxc3a, d3a, and c5a of Zebrafish are absent from the pharyngeal arches, hoxa4a, d4a, and b5a show divergent expression patterns from their orthologs in Medaka and Tilapia. These observed divergences may be, in part, responsible for the divergent pharyngeal jaw apparatus structures exhibited by these fishes

The Impact of Demographic, Social, and Environmental Factors on the Development of Steroid-Responsive Meningitis-Arteritis (SRMA) in the United Kingdom

BACKGROUND: Steroid‐responsive meningitis‐arteritis (SRMA) is an inflammatory disease of dogs that is suspected to be immune‐mediated. The development of other immune‐mediated diseases has been linked to vaccinations, time of the year, geographic location, sex, neuter status, and breed. HYPOTHESIS/OBJECTIVES: To identify if the development of SRMA is associated with time of year, vaccination, geographic location, sex, neuter status, and breed. ANIMALS: Sixty SRMA cases and 180 controls, all ≤24 months of age and matched for year of presentation, from a referral hospital population in the United Kingdom. METHODS: Retrospective case‐control study with unconditional logistic regression analysis. RESULTS: Beagles (P = .001), Border Collies (P = .001), Boxers (P = .032), Jack Russell Terriers (P = .001), Weimaraners (P = .048), and Whippets (P < .001) had significantly greater odds of developing SRMA in this population of dogs. Vaccination, time of year, geographic category, sex, and neuter status did not increase the odds of developing SRMA. CONCLUSIONS AND CLINICAL IMPORTANCE: Only breed increased the odds of developing SRMA. It would be prudent to investigate the genetics of the identified breeds to help elucidate the etiopathogenesis of SRMA

Life History of Swordfish, Xiphias gladius, Caught in the Northern Gulf of Mexico

The current study examined 93 Swordfish, Xiphias gladius, (64 females, 27 males, 2 unknown) ranging in size from 77.6–246.3 cm lower jaw fork length (LJFL) from the northern Gulf of Mexico (GOM). Samples were collected between March and August in 2005–2007, 2017–2019 and 2021. Age estimates of 51 Swordfish resulted in a maximum observed age of 11 years (205.0 cm LJFL) and 7 years (190.4 cm LJFL) for females and males, respectively. Observed and back—calculated length—at—age data were fitted to 4 growth models (2— and 3— parameter von Bertalanffy, Gompertz, and logistic). The 2—parameter von Bertalanffy was the model that best fit the data (Linf = 210.2 cm LJFL, k = 0.25). Histological examination of gonadal tissue from 91 fish indicated that females reached 50% and 95% physiological maturity at 116 ± 6 cm LJFL and 143 ± 8 cm LJFL, respectively, corresponding to ages 2—3 years. All males \u3e82 cm LJFL were physiologically sexually mature. Only 10% of females were reproductively active, with spawning capable females captured in June. Reproductively active females exhibited asynchronous oocyte development indicating batch spawning. Most males (96%) were spawning capable from April–August. Philometra sp. infection was found in all ovaries examined (n = 16) but with low abundance (2.25 ± 0.42); male philometrids were more prevalent than females (91.7% and 66.7%, respectively). Swordfish in the northern GOM appear to achieve sexual maturity at a younger age, grow faster, and have shorter theoretical longevity than previous reports from other regions world—wide

NKp46 defines ovine cells that have characteristics corresponding to NK cells

Natural killer (NK) cells are well recognized as playing a key role in innate immune defence through cytokine production and cytotoxic activity; additionally recent studies have identified several novel NK cell functions. The ability to study NK cells in the sheep has been restricted due to a lack of specific reagents. We report the generation of a monoclonal antibody specific for ovine NKp46, a receptor which in a number of mammals is expressed exclusively in NK cells. Ovine NKp46+ cells represent a population that is distinct from CD4+ and γδ+ T-cells, B-cells and cells of the monocytic lineage. The NKp46+ cells are heterogenous with respect to expression of CD2 and CD8 and most, but not all, express CD16 - characteristics consistent with NK cell populations in other species. We demonstrate that in addition to populations in peripheral blood and secondary lymphoid organs, ovine NKp46+ populations are also situated at the mucosal surfaces of the lung, gastro-intestinal tract and non-gravid uterus. Furthermore, we show that purified ovine NKp46+ populations cultured in IL-2 and IL-15 have cytotoxic activity that could be enhanced by ligation of NKp46 in re-directed lysis assays. Therefore we conclude that ovine NKp46+ cells represent a population that by phenotype, tissue distribution and function correspond to NK cells and that NKp46 is an activating receptor in sheep as in other species