Gold nanoparticle interactions with endothelial cells cultured under physiological conditions

PEGylated gold nanoparticles (AuNPs) have an extended circulation time after intravenous injection in vivo and exhibit favorable properties for biosensing, diagnostic imaging, and cancer treatment. No impact of PEGylated AuNPs on the barrier forming properties of endothelial cells (ECs) has been reported, but recent studies demonstrated that unexpected effects on erythrocytes are observed. Almost all studies to date have been with static-cultured ECs. Herein, ECs maintained under physiological cyclic stretch and flow conditions and used to generate a blood–brain barrier model were exposed to 20 nm PEGylated AuNPs. An evaluation of toxic effects, cell stress, the release profile of pro-inflammatory cytokines, and blood–brain barrier properties showed that even under physiological conditions no obvious effects of PEGylated AuNPs on ECs were observed. These findings suggest that 20 nm-sized, PEGylated AuNPs may be a useful tool for biomedical applications, as they do not affect the normal function of healthy ECs after entering the blood stream

ISO LWS Spectroscopy of M82: A Unified Evolutionary Model

We present the first complete far-infrared spectrum (43 to 197 um) of M82, the brightest infrared galaxy in the sky, taken with the Long Wavelength Spectrometer of the Infrared Space Observatory (ISO). We detected seven fine structure emission lines, [OI] 63 and 145 um, [OIII] 52 and 88 um, [NII] 122 um, [NIII] 57 um and [CII] 158 um, and fit their ratios to a combination starburst and photo-dissociation region (PDR) model. The best fit is obtained with HII regions with n = 250 cm^{-3} and an ionization parameter of 10^{-3.5} and PDRs with n = 10^{3.3} cm^{-3} and a far-ultraviolet flux of G_o = 10^{2.8}. We applied both continuous and instantaneous starburst models, with our best fit being a 3-5 Myr old instantaneous burst model with a 100 M_o cut-off. We also detected the ground state rotational line of OH in absorption at 119.4 um. No excited level OH transitions are apparent, indicating that the OH is almost entirely in its ground state with a column density ~ 4x10^{14} cm^{-2}. The spectral energy distribution over the LWS wavelength range is well fit with a 48 K dust temperature and an optical depth, tau_{Dust} proportional to lambda^{-1}.Comment: 23 pages, 4 figures, accepted by ApJ, Feb. 1, 199

Determining effects of areca (betel) nut chewing in a prospective cohort of pregnant women in Madang Province, Papua New Guinea

BACKGROUND: Chewing areca nut (AN), also known as betel nut, is common in Asia and the South Pacific and the habit has been linked to a number of serious health problems including oral cancer. Use of AN in pregnancy has been associated with a reduction in mean birthweight in some studies, but this association and the relationship between AN chewing and other adverse pregnancy outcomes remain poorly understood. METHODS: We assessed the impact of AN chewing on adverse outcomes including stillbirth, low birthweight (LBW, <2,500 g) and anaemia at delivery (haemoglobin <11.0 g/dL) in a longitudinal cohort of 2,700 pregnant women residing in rural lowland Papua New Guinea (PNG) from November 2009 until February 2013. Chewing habits and participant characteristics were evaluated at first antenatal visit and women were followed until delivery. RESULTS: 83.3% [2249/2700] of pregnant women used AN, and most chewed on a daily basis (86.2% [1939/2249]. Smoking and alcohol use was reported by 18.9% (511/2700) and 5.0% (135/2688) of women, respectively. AN use was not associated with pregnancy loss or congenital abnormalities amongst women with a known pregnancy outcome (n = 2215). Analysis of 1769 birthweights did not demonstrate an association between AN and LBW (chewers: 13.7% [200/1459] vs. non-chewers: 14.5% [45/310], P = 0.87) or reduced mean birthweight (2957 g vs. 2966 g; P = 0.76). Women using AN were more likely to be anaemic (haemoglobin <11 g/dL) at delivery (75.2% [998/1314] vs. 63.9% [182/285], adjusted odds ratio [95% CI]: 1.67 [1.27, 2.20], P < 0.001). Chewers more commonly had male babies than non-chewers (46.1% [670/1455] vs. 39.8% [123/309], P = 0.045). CONCLUSIONS: AN chewing may contribute to anaemia. Although not associated with other adverse pregnancy outcome in this cohort gestational AN use should be discouraged, given the potential adverse effects on haemoglobin and well-established long-term health risk including oral cancer. Future research evaluating the potential association of AN use and anaemia may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01136850 (06 April 2010)

Mitochondrial Genomes Reveal an Explosive Radiation of Extinct and Extant Bears near the Miocene-Pliocene Boundary

Background: Despite being one of the most studied families within the Carnivora, the phylogenetic relationships among the members of the bear family (Ursidae) have long remained unclear. Widely divergent topologies have been suggested based on various data sets and methods. Results: We present a fully resolved phylogeny for ursids based on ten complete mitochondrial genome sequences from all eight living and two recently extinct bear species, the European cave bear (Ursus spelaeus) and the American giant short-faced bear (Arctodus simus). The mitogenomic data yield a well-resolved topology for ursids, with the sloth bear at the basal position within the genus Ursus. The sun bear is the sister taxon to both the American and Asian black bears, and this clade is the sister clade of cave bear, brown bear and polar bear confirming a recent study on bear mitochondrial genomes. Conclusion: Sequences from extinct bears represent the third and fourth Pleistocene species for which complete mitochondrial genomes have been sequenced. Moreover, the cave bear specimen demonstrates that mitogenomic studies can be applied to Pleistocene fossils that have not been preserved in permafrost, and therefore have a broad application within ancient DNA research. Molecular dating of the mtDNA divergence times suggests a rapid radiation of bears in both the Old and New Worlds around 5 million years ago, at the Miocene-Pliocene boundary. This coincides with major global changes, such as the Messinian crisis and the first opening of the Bering Strait, and suggests a global influence of such events on species radiations

Maternal Malaria and Malnutrition (M3) initiative, a pooled birth cohort of 13 pregnancy studies in Africa and the Western Pacific.

PURPOSE: The Maternal Malaria and Malnutrition (M3) initiative has pooled together 13 studies with the hope of improving understanding of malaria-nutrition interactions during pregnancy and to foster collaboration between nutritionists and malariologists. PARTICIPANTS: Data were pooled on 14 635 singleton, live birth pregnancies from women who had participated in 1 of 13 pregnancy studies. The 13 studies cover 8 countries in Africa and Papua New Guinea in the Western Pacific conducted from 1996 to 2015. FINDINGS TO DATE: Data are available at the time of antenatal enrolment of women into their respective parent study and at delivery. The data set comprises essential data such as malaria infection status, anthropometric assessments of maternal nutritional status, presence of anaemia and birth weight, as well as additional variables such gestational age at delivery for a subset of women. Participating studies are described in detail with regard to setting and primary outcome measures, and summarised data are available from each contributing cohort. FUTURE PLANS: This pooled birth cohort is the largest pregnancy data set to date to permit a more definite evaluation of the impact of plausible interactions between poor nutritional status and malaria infection in pregnant women on fetal growth and gestational length. Given the current comparative lack of large pregnancy cohorts in malaria-endemic settings, compilation of suitable pregnancy cohorts is likely to provide adequate statistical power to assess malaria-nutrition interactions, and could point towards settings where such interactions are most relevant. The M3 cohort may thus help to identify pregnant women at high risk of adverse outcomes who may benefit from tailored intensive antenatal care including nutritional supplements and alternative or intensified malaria prevention regimens, and the settings in which these interventions would be most effective

Sulphadoxine-pyrimethamine plus azithromycin may improve birth outcomes through impacts on inflammation and placental angiogenesis independent of malarial infection

Abstract Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP) and SP plus azithromycin (SPAZ) reduces low birthweight (<2,500 g) in women without malarial and reproductive tract infections. This study investigates the impact of SPAZ on associations between plasma biomarkers of inflammation and angiogenesis and adverse pregnancy outcomes in 2,012 Papua New Guinean women. Concentrations of C-reactive protein (CRP), α-1-acid glycoprotein (AGP), soluble endoglin (sEng), soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured at enrolment and delivery in a trial comparing SPAZ to SP plus chloroquine (SPCQ). At antenatal enrolment higher CRP (adjusted odds ratio 1.52; 95% confidence interval [CI] 1.03–2.25), sEng (4.35; 1.77, 10.7) and sFlt1 (2.21; 1.09, 4.48) were associated with preterm birth, and higher sEng with low birthweight (1.39; 1.11,3.37), in SPCQ recipients only. Increased enrolment sFlt1:PlGF ratios associated with LBW in all women (1.46; 1.11, 1.90). At delivery, higher AGP levels were strongly associated with low birthweight, preterm birth and small-for-gestational age babies in the SPCQ arm only. Restricting analyses to women without malaria infection did not materially alter these relationships. Women receiving SPAZ had lower delivery AGP and CRP levels (p < 0.001). SPAZ may protect against adverse pregnancy outcomes by reducing inflammation and preventing its deleterious consequences, including dysregulation of placental angiogenesis, in women with and without malarial infection

High prevalence of NMDA receptor IgA/IgM antibodies in different dementia types

OBJECTIVE: To retrospectively determine the frequency of N-Methyl-D-Aspartate (NMDA) receptor (NMDAR) autoantibodies in patients with different forms of dementia. METHODS: Clinical characterization of 660 patients with dementia, neurodegenerative disease without dementia, other neurological disorders and age-matched healthy controls combined with retrospective analysis of serum or cerebrospinal fluid (CSF) for the presence of NMDAR antibodies. Antibody binding to receptor mutants and the effect of immunotherapy were determined in a subgroup of patients. RESULTS: Serum NMDAR antibodies of IgM, IgA, or IgG subtypes were detected in 16.1% of 286 dementia patients (9.5% IgM, 4.9% IgA, and 1.7% IgG) and in 2.8% of 217 cognitively healthy controls (1.9% IgM and 0.9% IgA). Antibodies were rarely found in CSF. The highest prevalence of serum antibodies was detected in patients with “unclassified dementia” followed by progressive supranuclear palsy, corticobasal syndrome, Parkinson’s disease-related dementia, and primary progressive aphasia. Among the unclassified dementia group, 60% of 20 patients had NMDAR antibodies, accompanied by higher frequency of CSF abnormalities, and subacute or fluctuating disease progression. Immunotherapy in selected prospective cases resulted in clinical stabilization, loss of antibodies, and improvement of functional imaging parameters. Epitope mapping showed varied determinants in patients with NMDAR IgA-associated cognitive decline. INTERPRETATION: Serum IgA/IgM NMDAR antibodies occur in a significant number of patients with dementia. Whether these antibodies result from or contribute to the neurodegenerative disorder remains unknown, but our findings reveal a subgroup of patients with high antibody levels who can potentially benefit from immunotherapy

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO