Recurrent triploidy due to a failure to complete maternal meiosis II: whole-exome sequencing reveals candidate variants

Triploidy is a relatively common cause of miscarriage; however, recurrent triploidy has rarely been reported. A healthy 34-year-old woman was ascertained because of 18 consecutive miscarriages with triploidy found in all 5 karyotyped losses. Molecular results in a sixth loss were also consistent with triploidy. Genotyping of markers near the centromere on multiple chromosomes suggested that all six triploid conceptuses occurred as a result of failure to complete meiosis II (MII). The proband's mother had also experienced recurrent miscarriage, with a total of 18 miscarriages. Based on the hypothesis that an inherited autosomal-dominant maternal predisposition would explain the phenotype, whole-exome sequencing of the proband and her parents was undertaken to identify potential candidate variants. After filtering for quality and rarity, potentially damaging variants shared between the proband and her mother were identified in 47 genes. Variants in genes coding for proteins implicated in oocyte maturation, oocyte activation or polar body extrusion were then prioritized. Eight of the most promising candidate variants were confirmed by Sanger sequencing. These included a novel change in the PLCD4 gene, and a rare variant in the OSBPL5 gene, which have been implicated in oocyte activation upon fertilization and completion of MII. Several variants in genes coding proteins playing a role in oocyte maturation and early embryonic development were also identified. The genes identified may be candidates for the study in other women experiencing recurrent triploidy or recurrent IVF failur

New Insights into White-Light Flare Emission from Radiative-Hydrodynamic Modeling of a Chromospheric Condensation

(abridged) The heating mechanism at high densities during M dwarf flares is poorly understood. Spectra of M dwarf flares in the optical and near-ultraviolet wavelength regimes have revealed three continuum components during the impulsive phase: 1) an energetically dominant blackbody component with a color temperature of T $\sim$ 10,000 K in the blue-optical, 2) a smaller amount of Balmer continuum emission in the near-ultraviolet at lambda $<$ 3646 Angstroms and 3) an apparent pseudo-continuum of blended high-order Balmer lines. These properties are not reproduced by models that employ a typical "solar-type" flare heating level in nonthermal electrons, and therefore our understanding of these spectra is limited to a phenomenological interpretation. We present a new 1D radiative-hydrodynamic model of an M dwarf flare from precipitating nonthermal electrons with a large energy flux of $10^{13}$ erg cm$^{-2}$ s$^{-1}$. The simulation produces bright continuum emission from a dense, hot chromospheric condensation. For the first time, the observed color temperature and Balmer jump ratio are produced self-consistently in a radiative-hydrodynamic flare model. We find that a T $\sim$ 10,000 K blackbody-like continuum component and a small Balmer jump ratio result from optically thick Balmer and Paschen recombination radiation, and thus the properties of the flux spectrum are caused by blue light escaping over a larger physical depth range compared to red and near-ultraviolet light. To model the near-ultraviolet pseudo-continuum previously attributed to overlapping Balmer lines, we include the extra Balmer continuum opacity from Landau-Zener transitions that result from merged, high order energy levels of hydrogen in a dense, partially ionized atmosphere. This reveals a new diagnostic of ambient charge density in the densest regions of the atmosphere that are heated during dMe and solar flares.Comment: 50 pages, 2 tables, 13 figures. Accepted for publication in the Solar Physics Topical Issue, "Solar and Stellar Flares". Version 2 (June 22, 2015): updated to include comments by Guest Editor. The final publication is available at Springer via http://dx.doi.org/10.1007/s11207-015-0708-

Low-energy excitations, symmetry breaking and specific heat in YbBiPt

The heavy fermion compound YbBiPt has a very large linear coefficient of specific heat {gamma} = 8 Jmol{sup {minus}1} K{sup {minus}2} and this is understood, to first order, in terms of the observed low-energy neutron scattering response. However, at low temperatures, symmetry forbidden splittings at 1 and 2 meV respectively are observed. These levels give good qualitative agreement with the measured specific heat, but poor quantitative agreement. Indeed, the specific heat drops more rapidly with temperature that can be accounted for assuming a temperature-independent density of states. The authors also present new low-temperature crystallographic data, which rule out any significant structural distortions

Evolution of the Neckeraceae (Bryophyta): resolving the backbone phylogeny

Earlier phylogenetic studies, including species belonging to the Neckeraceae, have indicated that this pleurocarpous moss family shares a strongly supported sister group relationship with the Lembophyllaceae, but the family delimitation of the former needs adjustment. To test the monophyly of the Neckeraceae, as well as to redefine the family circumscription and to pinpoint its phylogenetic position in a larger context, a phylogenetic study based on molecular data was carried out. Sequence data were compiled, combining data from all three genomes: nuclear ITS1 and 2, plastid trnS-rps4-trnT-trnL-trnF and rpl16, and mitochondrial nad5 intron. The Neckeraceae have sometimes been divided into the two families, Neckeraceae and Thamnobryaceae, a division rejected here. Both parsimony and Bayesian analyses of molecular data revealed that the family concept of the Neckeraceae needs several further adjustments, such as the exclusion of some individual species and smaller genera as well as the inclusion of the Leptodontaceae. Within the family three well-supported clades (A, B and C) can be distinguished. Members of clade A are mainly non-Asiatic and nontropical. Most species have a weak costa and immersed capsules with reduced peristomes (mainly Neckera spp.) and the teeth at the leaf margins are usually unicellular. Clade B members are also mainly non-Asiatic. They are typically fairly robust, distinctly stipilate, having a single, at least relatively strong costa, long setae (capsules exserted), and the peristomes are well developed or only somewhat reduced. Members of clade C are essentially Asiatic and tropical. The species of this clade usually have a strong costa and a long seta, the seta often being mammillose in its upper part. The peristome types in this clade are mixed, since both reduced and unreduced types are found. Several neckeraceous genera that were recognised on a morphological basis are polyphyletic (e.g. Neckera, Homalia, Thamnobryum, Porotrichum). Ancestral state reconstructions revealed that currently used diagnostic traits, such as the leaf asymmetry and costa strength are highly homoplastic. Similarly, the reconstructions revealed that the 'reduced' sporophyte features have evolved independently in each of the three clades.Earlier phylogenetic studies, including species belonging to the Neckeraceae, have indicated that this pleurocarpous moss family shares a strongly supported sister group relationship with the Lembophyllaceae, but the family delimitation of the former needs adjustment. To test the monophyly of the Neckeraceae, as well as to redefine the family circumscription and to pinpoint its phylogenetic position in a larger context, a phylogenetic study based on molecular data was carried out. Sequence data were compiled, combining data from all three genomes: nuclear ITS1 and 2, plastid trnS-rps4-trnT-trnL-trnF and rpl16, and mitochondrial nad5 intron. The Neckeraceae have sometimes been divided into the two families, Neckeraceae and Thamnobryaceae, a division rejected here. Both parsimony and Bayesian analyses of molecular data revealed that the family concept of the Neckeraceae needs several further adjustments, such as the exclusion of some individual species and smaller genera as well as the inclusion of the Leptodontaceae. Within the family three well-supported clades (A, B and C) can be distinguished. Members of clade A are mainly non-Asiatic and nontropical. Most species have a weak costa and immersed capsules with reduced peristomes (mainly Neckera spp.) and the teeth at the leaf margins are usually unicellular. Clade B members are also mainly non-Asiatic. They are typically fairly robust, distinctly stipilate, having a single, at least relatively strong costa, long setae (capsules exserted), and the peristomes are well developed or only somewhat reduced. Members of clade C are essentially Asiatic and tropical. The species of this clade usually have a strong costa and a long seta, the seta often being mammillose in its upper part. The peristome types in this clade are mixed, since both reduced and unreduced types are found. Several neckeraceous genera that were recognised on a morphological basis are polyphyletic (e.g. Neckera, Homalia, Thamnobryum, Porotrichum). Ancestral state reconstructions revealed that currently used diagnostic traits, such as the leaf asymmetry and costa strength are highly homoplastic. Similarly, the reconstructions revealed that the 'reduced' sporophyte features have evolved independently in each of the three clades.Earlier phylogenetic studies, including species belonging to the Neckeraceae, have indicated that this pleurocarpous moss family shares a strongly supported sister group relationship with the Lembophyllaceae, but the family delimitation of the former needs adjustment. To test the monophyly of the Neckeraceae, as well as to redefine the family circumscription and to pinpoint its phylogenetic position in a larger context, a phylogenetic study based on molecular data was carried out. Sequence data were compiled, combining data from all three genomes: nuclear ITS1 and 2, plastid trnS-rps4-trnT-trnL-trnF and rpl16, and mitochondrial nad5 intron. The Neckeraceae have sometimes been divided into the two families, Neckeraceae and Thamnobryaceae, a division rejected here. Both parsimony and Bayesian analyses of molecular data revealed that the family concept of the Neckeraceae needs several further adjustments, such as the exclusion of some individual species and smaller genera as well as the inclusion of the Leptodontaceae. Within the family three well-supported clades (A, B and C) can be distinguished. Members of clade A are mainly non-Asiatic and nontropical. Most species have a weak costa and immersed capsules with reduced peristomes (mainly Neckera spp.) and the teeth at the leaf margins are usually unicellular. Clade B members are also mainly non-Asiatic. They are typically fairly robust, distinctly stipilate, having a single, at least relatively strong costa, long setae (capsules exserted), and the peristomes are well developed or only somewhat reduced. Members of clade C are essentially Asiatic and tropical. The species of this clade usually have a strong costa and a long seta, the seta often being mammillose in its upper part. The peristome types in this clade are mixed, since both reduced and unreduced types are found. Several neckeraceous genera that were recognised on a morphological basis are polyphyletic (e.g. Neckera, Homalia, Thamnobryum, Porotrichum). Ancestral state reconstructions revealed that currently used diagnostic traits, such as the leaf asymmetry and costa strength are highly homoplastic. Similarly, the reconstructions revealed that the 'reduced' sporophyte features have evolved independently in each of the three clades.Peer reviewe

Nonmagnetic crystal-electric-field ground state in the heavy-fermion compound PrInAg{sub 2}

The authors have performed inelastic neutron scattering measurements that confirm that the crystal-electric-field split ground state in the heavy-fermion compound PrInAg{sub 2} is a nonmagnetic, non-Kramers doublet. This implies that a quadrupolar Kondo interaction is responsible for the enhanced thermodynamic properties observed at low temperatures. They also observe anomalous broadening of the inelastic peaks and suggest two possible causes for this broadening

ATP stimulates MMP-2 release from human aortic smooth muscle cells via JNK signaling pathway

Aortic smooth muscle cell release of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) has been implicated in aortic aneurysm pathogenesis, but proximal modulation of release is poorly understood. Extracellular nucleotides regulate vascular smooth muscle cell metabolism in response to physiochemical stresses, but nucleotide modulation of MMP and/or TIMP release has not been reported. We hypothesized that nucleotides modulate MMP-2 and TIMP-2 release from human aortic smooth muscle cells (HASMCs) via distinct purinergic receptors and signaling pathways. We exposed HASMCs to exogenous ATP and other nucleotides with and without interleukin-1β (IL-1β). HASMCs were pretreated in some experiments with apyrase, which degrades ATP, and inhibitors of ERK1/2, JNK, and p38 MAPK. MMP-2 and TIMP-2 released into supernatant were assessed using ELISA and Western blotting. ATP, adenosine, and UTP significantly stimulated MMP-2 release in the presence of IL-1β (300 nM ATP: 181 ± 22%, P = 0.003; 30 μm adenosine: 244 ± 150%, P = 0.001; and 200 μm UTP: 153 ± 40%, P = 0.015; vs. 100% constitutive). ATP also stimulated MMP-2 release in the absence of IL-1β (100 μm ATP: 148 ± 38% vs. 100% constitutive). Apyrase significantly reduced ATP-stimulated MMP-2 release (apyrase + 500 nM ATP: 59 ± 3% vs. 124 ± 7% with 500 nM ATP). Rank-order agonist potency for MMP-2 release was consistent with ATP activation of PAY and PAY receptors. ATP induced phosphorylation of intracellular JNK, and inhibition of the JNK pathway blocked ATP-stimulated MMP-2 release, indicating signaling via this pathway. Nucleotides are thus novel stimulants of MMP-2 release from HASMCs and may provide a mechanistic link between physiochemical stress in the aorta and aneurysms, especially in the context of inflammation

Mechanical ventilation alters airway nucleotides and purinoceptors in lung and extrapulmonary organs

Extracellular nucleotides are stress-responsive ligands that mediate a variety of cellular processes via purinoceptors. We hypothesized that mechanical ventilation (MV) would alter the extracellular adenyl-nucleotide profile and purinoceptor expression in lung and extrapulmonary tissues. Twenty-eight rats were randomized to: (i) unventilated control animals; (ii) tidal volume (V T; 6 ml/kg); (iii) VT (6 ml/kg) and positive end-expiratory pressure (PEEP; 5 cm H2O); (iv) VT (12 ml/kg); or (v) VT (12 ml/kg) and PEEP (5 cm H2O). Bronchoalveolar lavage (BAL) was analyzed for adenyl-nucleotides. Pulmonary, hepatic, and renal tissues were assessed for P2Y4, P 2Y6, P2X7, A3, and A 2b receptor expression by real-time reverse transcriptase-polymerase chain reaction and Fas/Fas ligand mRNA was quantified in the lung. MV produced volume-dependent changes in BAL nucleotides; AMP and adenosine increased, whereas ATP and ADP proportions decreased. Large-volume MV increased A 2b mRNA and decreased P2X7 in the lung; mRNA changes in lung Fas ligand paralleled P2X7. PEEP normalized BAL nucleotide profiles and A2b expression. Injurious MV reduced hepatic and renal P2X7 mRNA; PEEP normalized these levels in both tissues. Large-volume MV also decreased renal A2b mRNA. MV alters the BAL adenyl-nucleotide profile and purinoceptor patterns in lung, liver, and kidney. PEEP normalizes the BAL nucleotide profile and receptor patterns in lung and extrapulmonary tissues

An entomocentric view of the Janzen-Connell hypothesis

In 1987, in the first issue of Conservation Biology, Edward O. Wilson wrote about the “little things that run the world” – the importance and conservation of insects (Wilson, 1987). Readers of Insect Conservation and Diversity will no doubt be very familiar with the concept. Sadly, however, this perception is not as widely shared among the rest of the scientific community as it should be, and insects are still comparatively neglected as a prime focus of scientific investigations

The moulting arthropod: a complete genetic toolkit review.

Exoskeletons are a defining character of all arthropods that provide physical support for their segmented bodies and appendages as well as protection from the environment and predation. This ubiquitous yet evolutionarily variable feature has been instrumental in facilitating the adoption of a variety of lifestyles and the exploitation of ecological niches across all environments. Throughout the radiation that produced the more than one million described modern species, adaptability afforded by segmentation and exoskeletons has led to a diversity that is unrivalled amongst animals. However, because of the limited extensibility of exoskeleton chitin and cuticle components, they must be periodically shed and replaced with new larger ones, notably to accommodate the growing individuals encased within. Therefore, arthropods grow discontinuously by undergoing periodic moulting events, which follow a series of steps from the preparatory pre-moult phase to ecdysis itself and post-moult maturation of new exoskeletons. Each event represents a particularly vulnerable period in an arthropod's life cycle, so processes must be tightly regulated and meticulously executed to ensure successful transitions for normal growth and development. Decades of research in representative arthropods provide a foundation of understanding of the mechanisms involved. Building on this, studies continue to develop and test hypotheses on the presence and function of molecular components, including neuropeptides, hormones, and receptors, as well as the so-called early, late, and fate genes, across arthropod diversity. Here, we review the literature to develop a comprehensive overview of the status of accumulated knowledge of the genetic toolkit governing arthropod moulting. From biosynthesis and regulation of ecdysteroid and sesquiterpenoid hormones, to factors involved in hormonal stimulation responses and exoskeleton remodelling, we identify commonalities and differences, as well as highlighting major knowledge gaps, across arthropod groups. We examine the available evidence supporting current models of how components operate together to prepare for, execute, and recover from ecdysis, comparing reports from Chelicerata, Myriapoda, Crustacea, and Hexapoda. Evidence is generally highly taxonomically imbalanced, with most reports based on insect study systems. Biases are also evident in research on different moulting phases and processes, with the early triggers and late effectors generally being the least well explored. Our synthesis contrasts knowledge based on reported observations with reasonably plausible assumptions given current taxonomic sampling, and exposes weak assumptions or major gaps that need addressing. Encouragingly, advances in genomics are driving a diversification of tractable study systems by facilitating the cataloguing of putative genetic toolkits in previously under-explored taxa. Analysis of genome and transcriptome data supported by experimental investigations have validated the presence of an "ultra-conserved" core of arthropod genes involved in moulting processes. The molecular machinery has likely evolved with elaborations on this conserved pathway backbone, but more taxonomic exploration is needed to characterise lineage-specific changes and novelties. Furthermore, linking these to transformative innovations in moulting processes across Arthropoda remains hampered by knowledge gaps and hypotheses based on untested assumptions. Promisingly however, emerging from the synthesis is a framework that highlights research avenues from the underlying genetics to the dynamic molecular biology through to the complex physiology of moulting