When two is better than one: Differences in characteristics of women using condoms only compared to those using condoms combined with an effective contraceptive

published_or_final_versio

Perfluorooctanoic Acid–Induced Immunomodulation in Adult C57BL/6J or C57BL/6N Female Mice

BackgroundPerfluorooctanoic acid (PFOA), an environmentally persistent compound of regulatory concern, has been reported to reduce antibody responses in mice at a single dose.ObjectiveThe aim of this study was to evaluate PFOA effects on humoral and cellular immunity using standard assays for assessing immune function, and to derive dose–response data.MethodsC57BL/6J mice received 0 or 30 mg PFOA/kg/day for 10 days; half of the exposed groups were switched to vehicle and half continued on PFOA for five days. C57BL/6N mice received 0–30 mg/kg/day of PFOA in drinking water for 15 days. Mice were immunized with sheep red blood cells or sensitized to bovine serum albumin in Freund’s complete adjuvant on day 10 of exposure; immune responses were determined 1 day post-exposure.ResultsWe found that 30 mg PFOA/kg/day given for 10 or 15 days reduced IgM synthesis; serum collected 1 day postexposure contained 8.4 × 104 or 2.7 × 105 ng PFOA/mL, respectively. IgM synthesis was suppressed at exposures ≥ 3.75 mg PFOA/kg/day in a dose-dependent manner, and IgG titers were elevated at 3.75 and 7.5 mg PFOA/kg/day. Serum PFOA at 3.75 mg/kg/day was 7.4 × 104 ng/mL 1 day postexposure, or 150-fold greater than the levels reported in individuals living near a PFOA production site. Using a second-degree polynomial model, we calculated a benchmark dose of 3 mg/kg/day, with a lower bound (95% confidence limit) of 1.75 mg/kg/day. Cell-mediated function was not affected.ConclusionsIgM antibodies were suppressed after PFOA exposure. The margin of exposure for reduced IgM antibody synthesis was approximately 150 for highly exposed human populations

Fungsi Sosiologis Undang-undang Dasar Negara Republik Indonesia Tahun 1945 Dalam Memenuhi Hak-hak Masyarakat

Constitution is a binding social contract between government and citizen. Their relationships figure the rights of the society. These rightsbecome the tool of society to participate in making government policy, to control the governmentand to avoid the practice of absolutpower.Therefore, the 1945 Indonesian Constitution regulates the norms of rights of society. The functions of the rights are to up hold society justice as well as to create society welfare. The regulation of rights of society in Indonesian Constitution indicates itssociological function.It accommodates the right of society in its relationship between government and citizen

External perceptions of successful university brands

Branding in universities has become an increasingly topical issue, with some institutions committing substantial financial resources to branding activities. The particular characteristics of the sector present challenges for those seeking to build brands and it therefore seems to be timely and appropriate to investigate the common approaches of those institutions perceived as having successful brands. This study is exploratory in nature, seeking to investigate how successfully UK universities brand themselves, whether they are distinct and if the sector overall communicates effectively. This is approached through examining the perspective of opinion formers external to universities but closely involved with the sector – a key stakeholder group in UK higher education Overall, the research’s exploratory nature aims to further the debate on effective branding in UK higher education. The findings and conclusions identify some issues surrounding university branding activity; most UK universities were considered to be distinct from one another, but few were seen to have real fully formed brands. Although a number of institutions that were seen as having more ‘successful’ brands were identified, it was argued that whilst many UK universities communicate their brand well enough to key stakeholders, they fail to consistently do this across all audiences. It was also suggested that UK universities may concentrate on areas of perceived immediate strategic importance (in terms of branding) to an extent where others are neglected

Discoidin domain receptor 1 kinase activity is required for regulating collagen IV synthesis

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds to and is activated by collagens. DDR1 expression increases following kidney injury and accumulating evidence suggests that it contributes to the progression of injury. To this end, deletion of DDR1 is beneficial in ameliorating kidney injury induced by angiotensin infusion, unilateral ureteral obstruction, or nephrotoxic nephritis. Most of the beneficial effects observed in the DDR1-null mice are attributed to reduced inflammatory cell infiltration to the site of injury, suggesting that DDR1 plays a pro-inflammatory effect. The goal of this study was to determine whether, in addition to its pro-inflammatory effect, DDR1 plays a deleterious effect in kidney injury by directly regulating extracellular matrix production. We show that DDR1-null mice have reduced deposition of glomerular collagens I and IV as well as decreased proteinuria following the partial renal ablation model of kidney injury. Using mesangial cells isolated from DDR1-null mice, we show that these cells produce significantly less collagen compared to DDR1-null cells reconstituted with wild type DDR1. Moreover, mutagenesis analysis revealed that mutations in the collagen binding site or in the kinase domain significantly reduce DDR1-mediated collagen production. Finally, we provide evidence that blocking DDR1 kinase activity with an ATP-competitive small molecule inhibitor reduces collagen production. In conclusion, our studies indicate that the kinase activity of DDR1 plays a key role in DDR1-induced collagen synthesis and suggest that blocking collagen-mediated DDR1 activation may be beneficial in fibrotic diseases

A systematic review of biomarkers for disease progression in Parkinson's disease

Peer reviewedPublisher PD

BASS. XXXIV. A Catalog of the Nuclear Millimeter-wave Continuum Emission Properties of AGNs Constrained on Scales ≤ 100-200 pc

We present a catalog of the millimeter-wave (mm-wave) continuum properties of 98 nearby (z < 0.05) active galactic nuclei (AGNs) selected from the 70 month Swift/BAT hard-X-ray catalog that have precisely determined X-ray spectral properties and subarcsecond-resolution Atacama Large Millimeter/submillimeter Array Band 6 (211-275 GHz) observations as of 2021 April. Due to the hard-X-ray (>10 keV) selection, the sample is nearly unbiased for obscured systems at least up to Compton-thick-level obscuration, and provides the largest number of AGNs with high-physical-resolution mm-wave data (less than or similar to 100-200 pc). Our catalog reports emission peak coordinates, spectral indices, and peak fluxes and luminosities at 1.3 mm (230 GHz). Additionally, high-resolution mm-wave images are provided. Using the images and creating radial surface brightness profiles of mm-wave emission, we identify emission extending from the central sources and isolated blob-like emission. Flags indicating the presence of these emission features are tabulated. Among 90 AGNs with significant detections of nuclear emission, 37 AGNs (approximate to 41%) appear to have both or one of extended or blob-like components. We, in particular, investigate AGNs that show well-resolved mm-wave components and find that these seem to have a variety of origins (i.e., a jet, radio lobes, a secondary AGN, stellar clusters, a narrow-line region, galaxy disk, active star formation regions, or AGN-driven outflows), and some components have currently unclear origins

BASS. XLII. The Relation between the Covering Factor of Dusty Gas and the Eddington Ratio in Nearby Active Galactic Nuclei

Accreting supermassive black holes (SMBHs) located at the centers of galaxies are typically surrounded by large quantities of gas and dust. The structure and evolution of this circumnuclear material can be studied at different wavelengths, from the submillimeter to the X-ray. Recent X-ray studies have shown that the covering factor of the obscuring material tends to decrease with increasing Eddington ratio, likely due to radiative feedback on dusty gas. Here we study a sample of 549 nearby (z less than or similar to 0.1) hard X-ray (14-195 keV) selected nonblazar active galactic nuclei (AGN) and use the ratio between the AGN infrared and bolometric luminosity as a proxy of the covering factor. We find that, in agreement with what has been found by X-ray studies of the same sample, the covering factor decreases with increasing Eddington ratio. We also confirm previous findings that showed that obscured AGN typically have larger covering factors than unobscured sources. Finally, we find that the median covering factors of AGN located in different regions of the column density-Eddington ratio diagram are in good agreement with what would be expected from a radiation-regulated growth of SMBHs

The spectral, spatial and contrast sensitivity of human polarization pattern perception

It is generally believed that humans perceive linear polarized light following its conversion into a luminance signal by diattenuating macular structures. Measures of polarization sensitivity may therefore allow a targeted assessment of macular function. Our aim here was to quantify psychophysical characteristics of human polarization perception using grating and optotype stimuli defined solely by their state of linear polarization. We show: (i) sensitivity to polarization patterns follows the spectral sensitivity of macular pigment; (ii) the change in sensitivity across the central field follows macular pigment density; (iii) polarization patterns are identifiable across a range of contrasts and scales, and can be resolved with an acuity of 15.4 cycles/degree (0.29 logMAR); and (iv) the human eye can discriminate between areas of linear polarization differing in electric field vector orientation by as little as 4.4°. These findings, which support the macular diattenuator model of polarization sensitivity, are unique for vertebrates and approach those of some invertebrates with a well-developed polarization sense. We conclude that this sensory modality extends beyond Haidinger's brushes to the recognition of quantifiable spatial polarization-modulated patterns. Furthermore, the macular origin and sensitivity of human polarization pattern perception makes it potentially suitable for the detection and quantification of macular dysfunction

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio