Antibodies to acetylcholine receptor in parous women with myasthenia: evidence for immunization by fetal antigen

The weakness in myasthenia gravis (MG) is mediated by autoantibodies against adult muscle acetylcholine receptors (AChR) at the neuromuscular junction; most of these antibodies also bind to fetal AChR, which is present in the thymus. In rare cases, babies of mothers with MG, or even of asymptomatic mothers, develop a severe developmental condition, arthrogryposis multiplex congenita, caused by antibodies that inhibit the ion channel function of the fetal AChR while not affecting the adult AChR. Here we show that these fetal AChR inhibitory antibodies are significantly more common in females sampled after pregnancy than in those who present before pregnancy, suggesting that they may be induced by the fetus. Moreover, we were able to clone high-affinity combinatorial Fab antibodies from thymic cells of two mothers with MG who had babies with arthrogryposis multiplex congenita. These Fabs were highly specific for fetal AChR and did not bind the main immunogenic region that is common to fetal and adult AChR. The Fabs show strong biases to VH3 heavy chains and to a single Vk1 light chain in one mother. Nevertheless, they each show extensive intraclonal diversification from a highly mutated consensus sequence, consistent with antigen-driven selection in successive steps. Collectively, our results suggest that, in some cases of MG, initial immunization against fetal AChR is followed by diversification and expansion of B cells in the thymus; maternal autoimmunity will result if the immune response spreads to the main immunogenic region and other epitopes common to fetal and adult AChR

Invasiveness of plants is predicted by size and fecundity in the native range

This is the final version of the article. Available from Wiley via the DOI in this record.An important goal for invasive species research is to find key traits of species that predispose them to being invasive outside their native range. Comparative studies have revealed phenotypic and demographic traits that correlate with invasiveness among plants. However, all but a few previous studies have been performed in the invaded range, an approach which potentially conflates predictors of invasiveness with changes that happen during the invasion process itself. Here, we focus on wild plants in their native range to compare life-history traits of species known to be invasive elsewhere, with their exported but noninvasive relatives. Specifically, we test four hypotheses: that invasive plant species (1) are larger; (2) are more fecund; (3) exhibit higher fecundity for a given size; and (4) attempt to make seed more frequently, than their noninvasive relatives in the native range. We control for the effects of environment and phylogeny using sympatric congeneric or confamilial pairs in the native range. We find that invasive species are larger than noninvasive relatives. Greater size yields greater fecundity, but we also find that invasives are more fecund per-unit-size. SYNTHESIS: We provide the first multispecies, taxonomically controlled comparison of size, and fecundity of invasive versus noninvasive plants in their native range. We find that invasive species are bigger, and produce more seeds, even when we account for their differences in size. Our findings demonstrate that invasive plant species are likely to be invasive as a result of both greater size and constitutively higher fecundity. This suggests that size and fecundity, relative to related species, could be used to predict which plants should be quarantined.We thank the National Trust and Cornwall Wildlife Trust for access to field sites, Dr. Colin French for use of the ERICA database, and Luke Davis and Cheryl Mills for assistance during data collection. KJ was supported by the University of Exeter as part of its wildlife research partnership with DEFRA's National Wildlife Management Centre. DH was supported by the Natural Environment Research Council grant reference NE/L007770/1

The stellar mass function of star-forming galaxies and the mass-dependent SFR function since z = 2.23 from HiZELS

We explore a large uniformly selected sample of Hα selected star-forming galaxies (SFGs) at z = 0.40, 0.84, 1.47, 2.23 to unveil the evolution of the star formation rate (SFR) function and the stellar mass function. We find strong evolution in the SFR function, with the typical SFR of SFGs declining exponentially in the last 11 Gyr as SFR*(T[Gyr]) = 104.23/T + 0.37 M⊙ yr−1, but with no evolution in the faint-end slope, α ≈ −1.6. The stellar mass function of SFGs, however, reveals little evolution: α ≈ −1.4, M* ∼ 1011.2 ± 0.2 M⊙ and just a slight increase of ∼2.3× in Φ* from z = 2.23 to z = 0.4. The stellar mass density within SFGs has been roughly constant since z = 2.23 at ∼107.65 ± 0.08 M⊙ Mpc−3, comprising ≈100 per cent of the stellar mass density in all galaxies at z = 2.23, and declining to ≈20 per cent by z = 0.40, driven by the rise of the passive population. We find that SFGs with ∼1010.0 ± 0.2 M⊙ contribute most to the SFR density (ρSFR) per d log10M, and that there is no significant evolution in the fractional contribution from SFGs of different masses to ρSFR or ρSFR(d log10M)−1 since z = 2.23. Instead, we show that the decline of SFR* and of ρSFR is primarily driven by an exponential decline in SFRs at all masses. Our results have important implications not only on how SFGs need to be quenched across cosmic time, but also on the driver(s) of the exponential decline in SFR* from ∼66 M⊙ yr−1 to 5 M⊙ yr−1 since z ∼ 2.23

Analytical modeling of micelle growth. 3. Electrostatic free energy of ionic wormlike micelles -- effects of activity coefficients and spatially confined electric double layers

Hypotheses: To correctly predict the aggregation number and size of wormlike micelles from ionic surfactants, the molecular-thermodynamic theory has to calculate the free energy per molecule in the micelle with accuracy better than 0.01 kT, which is a serious challenge. The problem could be solved if the effects of mutual confinement of micelle counterion atmospheres, as well as the effects of counterion binding, surface curvature and ionic interactions in the electric double layer (EDL), are accurately described. Theory: The electric field is calculated using an appropriate cell model, which takes into account the aforementioned effects. Expressions for the activity coefficients have been used, which vary across the EDL and describe the electrostatic, hard sphere, and specific interactions between the ions. New approach for fast numerical calculation of the electrostatic free energy is developed. Findings: The numerical results demonstrate the variation of quantities characterizing the EDL of cylindrical and spherical micelles with the rise of electrolyte concentration. The effect of activity coefficients leads to higher values of the free energy per surfactant molecule in the micelle as compared with the case of neglected ionic interactions. The results are essential for the correct prediction of the size of wormlike micelles from ionic surfactants. This study can be extended to mixed micelles of ionic and nonionic surfactants for interpretation of the observed synergistic effects.Comment: 36 pages, 6 figures, Supplementary Information: 12 pages, 1 figur

Designing Effective Habitat Studies: Quantifying Multiple Sources of Variability in Bat Activity

Common aims of habitat studies are to differentiate between (i) suitable and unsuitable sites for a given species, and (ii) sites used by different communities of species. To quantify differences between sites, field data of site use must be precise enough that true underlying between-site variability is not masked by within-site measurement error. We designed a pilot study to guide the development of a survey protocol for a habitat study on bats in an agricultural landscape in southeastern Australia. Three woodland sites and two scattered tree sites of 2 ha each were surveyed for nine consecutive nights. At three locations within each site (spaced > 50 m apart) one or two Anabat detectors were mounted 1 m above ground or in a tree (2 m above ground). We used mixed regression models to quantify multiple sources of variability in bat calling activity, and graphical data analysis to visualise how increases in survey effort were likely to affect inference. For the five most active species, we found that typically over 40% of variability in nightly detections occurred at the between-site level; approximately 10% occurred between locations within sites; approximately 20% was explained by night-to-night differences; and approximately 30% of variability was not attributable to systematic variation within experimental units. Differences in community composition between sites were clearly evident when two or more detectors per site were used for four or more nights. We conclude with six general considerations for the design of effective habitat studies. These are to (i) consider key contrasts of interest; (ii) use data from mild, calm, dry nights only; (iii) calibrate detectors; (iv) use multiple detectors where possible, or move a single detector within a site; (v) survey for multiple nights; and (vi) where vertical differentiation in habitat use is likely, mount detectors at different heights. These considerations need to be balanced within the context of financial and logistical constraints

The dynamics of z = 0.8 Hα-selected star-forming galaxies from KMOS/CF-HiZELS

We present the spatially resolved Hα dynamics of 16 star-forming galaxies at z ~ 0.81 using the new KMOS multi-object integral field spectrograph on the ESO Very Large Telescope. These galaxies, selected using 1.18 μm narrowband imaging from the 10 deg2 CFHT-HiZELS survey of the SA 22 hr field, are found in a ~4 Mpc overdensity of Hα emitters and likely reside in a group/intermediate environment, but not a cluster. We confirm and identify a rich group of star-forming galaxies at z = 0.813 ± 0.003, with 13 galaxies within 1000 km s–1 of each other, and seven within a diameter of 3 Mpc. All of our galaxies are "typical" star-forming galaxies at their redshift, 0.8 ± 0.4 SFR$^*_{z = 0.8}$, spanning a range of specific star formation rates (sSFRs) of 0.2-1.1 Gyr–1 and have a median metallicity very close to solar of 12 + log(O/H) = 8.62 ± 0.06. We measure the spatially resolved Hα dynamics of the galaxies in our sample and show that 13 out of 16 galaxies can be described by rotating disks and use the data to derive inclination corrected rotation speeds of 50-275 km s–1. The fraction of disks within our sample is 75% ± 8%, consistent with previous results based on Hubble Space Telescope morphologies of Hα-selected galaxies at z ~ 1 and confirming that disks dominate the SFR density at z ~ 1. Our Hα galaxies are well fitted by the z ~ 1-2 Tully-Fisher (TF) relation, confirming the evolution seen in the zero point. Apart from having, on average, higher stellar masses and lower sSFRs, our group galaxies at z = 0.81 present the same mass-metallicity and TF relation as z ~ 1 field galaxies and are all disk galaxies

The incidence and risk factors for new onset atrial fibrillation in the PROSPER study

Aims Atrial fibrillation/flutter (AF) is the most common arrhythmia in older people. It associates with reduced exercise capacity, increased risk of stroke, and mortality. We aimed to determine retrospectively whether pravastatin reduces the incidence of AF and whether any electrocardiographic measures or clinical conditions might be risk factors for its development. Methods and results The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) was a randomized, double-blind controlled trial that recruited 5804 individuals aged 70-82 years with a history of, or risk factors for, vascular disease. A total of 2891 were allocated to pravastatin and 2913 to placebo; mean follow-up was 3.2 years. Electrocardiograms (ECGs), which were recorded at baseline, annually thereafter, and at run-out, were processed by computer and reviewed manually. In all, 264 of 2912 (9.1%) of the placebo group and 283 of 2888 (9.8%) of the pravastatin-treated group developed AF [hazard ratio 1.08 (0.92,1.28), P = 0.35)]. Multivariate analysis showed that PR and QTc intervals, age, left ventricular hypertrophy, and ST-T abnormalities were related to development of AF after adjustment for many variables including alcohol consumption, which itself was univariately predictive of developing AF. Previous myocardial infarction on the ECG was not a risk factor. A history of vascular disease was strongly linked with developing AF but not diabetes and hypertension. Conclusion Pravastatin does not reduce the incidence of AF in older people at risk of vascular disease, at least in the short-medium term. Risk factors for AF include older age, prolongation of PR or QTc intervals, left ventricular hypertrophy, and ST-T abnormalities on the EC

A relationship between specific star formation rate and metallicity gradient within z ∼ 1 galaxies from KMOS-HiZELS

We have observed a sample of typical z ∼ 1 star-forming galaxies, selected from the HiZELS survey, with the new K-band Multi-Object Spectrograph (KMOS) near-infrared, multi-integral field unit instrument on the Very Large Telescope (VLT), in order to obtain their dynamics and metallicity gradients. The majority of our galaxies have a metallicity gradient consistent with being flat or negative (i.e. higher metallicity cores than outskirts). Intriguingly, we find a trend between metallicity gradient and specific star formation rate (sSFR), such that galaxies with a high sSFR tend to have relatively metal poor centres, a result which is strengthened when combined with data sets from the literature. This result appears to explain the discrepancies reported between different high-redshift studies and varying claims for evolution. From a galaxy evolution perspective, the trend we see would mean that a galaxy's sSFR is governed by the amount of metal-poor gas that can be funnelled into its core, triggered either by merging or through efficient accretion. In fact, merging may play a significant role as it is the starburst galaxies at all epochs, which have the more positive metallicity gradients. Our results may help to explain the origin of the fundamental metallicity relation, in which galaxies at a fixed mass are observed to have lower metallicities at higher star formation rates, especially if the metallicity is measured in an aperture encompassing only the central regions of the galaxy. Finally, we note that this study demonstrates the power of KMOS as an efficient instrument for large-scale resolved galaxy surveys