Stable isotope values in modern bryozoan carbonate from New Zealand and implications for paleoenvironmental interpretation

Bryozoan carbonate contains useful geochemical evidence of temperate shelf paleoenvironments. Stable isotope values were determined for 103 modern marine bryozoan skeletons representing 30 species from New Zealand. δ18O values range from -1.4 to 2.8 VPDB, while δ13C range from -4.5 to 2.8 VPDB (values uncorrected for mineralogical variation). These values are distinct from those of both tropical marine skeletons and New Zealand Tertiary fossils. Most bryozoans secrete carbonate in or near isotopic equilibrium with sea water, except for Celleporina and Steginoporella. The complex and variable mineralogies of the bryozoans reported here make correction for mineralogical effects problematic. Nevertheless, mainly aragonitic forms display higher isotope values, as anticipated. Both temperature and salinity constrain δ18O and δ13C values, and vary with latitude and water depth. Ten samples from a single branch of Cinctipora elegans from the Otago shelf cover a narrow range, although the striking difference in carbon isotope values between the endozone and exozone probably reflects different mineralisation histories. Our stable isotope results from three different laboratories on a single population from a single location are encouragingly consistent. Monomineralic bryozoans, when carefully chosen to avoid species suspected of vital fractionation, have considerable potential as geochemical paleoenvironmental indicators, particularly in temperate marine environments where bryozoans are dominant sediment producers

A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED

RATIONALE AND OBJECTIVES: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes. METHODS: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement. RESULTS: 9 GSVA signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper type 2 (Th-2) cytokines and lack of corticosteroid response (Group 1 and Group 3). Group 1 had the highest submucosal eosinophils, high exhaled nitric oxide (FeNO) levels, exacerbation rates and oral corticosteroid (OCS) use whilst Group 3 patients showed the highest levels of sputum eosinophils and had a high BMI. In contrast, Group 2 and Group 4 patients had an 86% and 64% probability of having non-eosinophilic inflammation. Using machine-learning tools, we describe an inference scheme using the currently-available inflammatory biomarkers sputum eosinophilia and exhaled nitric oxide levels along with OCS use that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity. CONCLUSION: This analysis demonstrates the usefulness of a transcriptomic-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target Th2-mediated inflammation and/or corticosteroid insensitivity

Eleanor Davies and the New Jerusalem

Eleanor Davies was a great believer in historical moments. In her first work—A Warning to the Dragon and All His Angels of 1625-she told readers that “The Lord is at the Dore.”1 This immanence of God made her watchful and purposeful, reading the signs in her daily life, counting days, weeks, and years because she believed that Christ would come again. His arrival had been predestined from the beginning of the world: “from the going forth of the Commandement, which is the beginning of the Creation to the building of the New Jerusalem, the second comming of Messiah, the Prince the Sonne of God, it shall be Seaven Weekes or Seaven Moneths.”2 For Davies, time was elastic, but history was absolute. What the biblical prophets (in this case Ezekiel) said would come to pass, really would come to pass, but their promises were oracular; they had complete authority but were also elusive. Davies accepted this. She knew that she was living in the latter days, but when it came to God’s final judgment, “the daye and houre knoweth no man.”3 God could not be known as such and what she called knowledge was a spiritual transformation that took place when “He powreth out his Spirit upon his hand-maidens,” like herself.4 This essay uses A Warning to the Dragon and Davies’ works of the 1630s and 1640s to examine her theology

From Euclidean Geometry to Knots and Nets

This document is the Accepted Manuscript of an article accepted for publication in Synthese. Under embargo until 19 September 2018. The final publication is available at Springer via https://doi.org/10.1007/s11229-017-1558-x.This paper assumes the success of arguments against the view that informal mathematical proofs secure rational conviction in virtue of their relations with corresponding formal derivations. This assumption entails a need for an alternative account of the logic of informal mathematical proofs. Following examination of case studies by Manders, De Toffoli and Giardino, Leitgeb, Feferman and others, this paper proposes a framework for analysing those informal proofs that appeal to the perception or modification of diagrams or to the inspection or imaginative manipulation of mental models of mathematical phenomena. Proofs relying on diagrams can be rigorous if (a) it is easy to draw a diagram that shares or otherwise indicates the structure of the mathematical object, (b) the information thus displayed is not metrical and (c) it is possible to put the inferences into systematic mathematical relation with other mathematical inferential practices. Proofs that appeal to mental models can be rigorous if the mental models can be externalised as diagrammatic practice that satisfies these three conditions.Peer reviewe

MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.

Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort

The Role of the Mucus Barrier in Digestion

Mucus forms a protective layer across a variety of epithelial surfaces. In the gastrointestinal (GI) tract, the barrier has to permit the uptake of nutrients, while excluding potential hazards, such as pathogenic bacteria. In this short review article, we look at recent literature on the structure, location, and properties of the mammalian intestinal secreted mucins and the mucus layer they form over a wide range of length scales. In particular, we look at the structure of the gel-forming glycoprotein MUC2, the primary intestinal secreted mucin, and the influence this has on the properties of the mucus layer. We show that, even at the level of the protein backbone, MUC2 is highly heterogeneous and that this is reflected in the networks it forms. It is evident that a combination of charge and pore size determines what can diffuse through the layer to the underlying gut epithelium. This information is important for the targeted delivery of bioactive molecules, including nutrients and pharmaceuticals, and for understanding how GI health is maintained

The Anatomy of the bill Tip of Kiwi and Associated Somatosensory Regions of the Brain: Comparisons with Shorebirds

Three families of probe-foraging birds, Scolopacidae (sandpipers and snipes), Apterygidae (kiwi), and Threskiornithidae (ibises, including spoonbills) have independently evolved long, narrow bills containing clusters of vibration-sensitive mechanoreceptors (Herbst corpuscles) within pits in the bill-tip. These ‘bill-tip organs’ allow birds to detect buried or submerged prey via substrate-borne vibrations and/or interstitial pressure gradients. Shorebirds, kiwi and ibises are only distantly related, with the phylogenetic divide between kiwi and the other two taxa being particularly deep. We compared the bill-tip structure and associated somatosensory regions in the brains of kiwi and shorebirds to understand the degree of convergence of these systems between the two taxa. For comparison, we also included data from other taxa including waterfowl (Anatidae) and parrots (Psittaculidae and Cacatuidae), non-apterygid ratites, and other probe-foraging and non probe-foraging birds including non-scolopacid shorebirds (Charadriidae, Haematopodidae, Recurvirostridae and Sternidae). We show that the bill-tip organ structure was broadly similar between the Apterygidae and Scolopacidae, however some inter-specific variation was found in the number, shape and orientation of sensory pits between the two groups. Kiwi, scolopacid shorebirds, waterfowl and parrots all shared hypertrophy or near-hypertrophy of the principal sensory trigeminal nucleus. Hypertrophy of the nucleus basorostralis, however, occurred only in waterfowl, kiwi, three of the scolopacid species examined and a species of oystercatcher (Charadriiformes: Haematopodidae). Hypertrophy of the principal sensory trigeminal nucleus in kiwi, Scolopacidae, and other tactile specialists appears to have co-evolved alongside bill-tip specializations, whereas hypertrophy of nucleus basorostralis may be influenced to a greater extent by other sensory inputs. We suggest that similarities between kiwi and scolopacid bill-tip organs and associated somatosensory brain regions are likely a result of similar ecological selective pressures, with inter-specific variations reflecting finer-scale niche differentiation

Diversity in olfactory bulb size in birds reflects allometry, ecology, and phylogeny

The relative size of olfactory bulbs (OBs) is correlated with olfactory capabilities across vertebrates and is widely used to assess the relative importance of olfaction to a species’ ecology. In birds, variations in the relative size of OBs are correlated with some behaviors; however, the factors that have led to the high level of diversity seen in OB sizes across birds are still not well understood. In this study, we use the relative size of OBs as a neuroanatomical proxy for olfactory capabilities in 135 species of birds, representing 21 orders. We examine the scaling of OBs with brain size across avian orders, determine likely ancestral states and test for correlations between OB sizes and habitat, ecology, and behavior. The size of avian OBs varied with the size of the brain and this allometric relationship was for the most part isometric, although species did deviate from this trend. Large OBs were characteristic of more basal species and in more recently derived species the OBs were small. Living and foraging in a semiaquatic environment was the strongest variable driving the evolution of large OBs in birds; olfaction may provide cues for navigation and foraging in this otherwise featureless environment. Some of the diversity in OB sizes was also undoubtedly due to differences in migratory behavior, foraging strategies and social structure. In summary, relative OB size in birds reflect allometry, phylogeny and behavior in ways that parallel that of other vertebrate classes. This provides comparative evidence that supports recent experimental studies into avian olfaction and suggests that olfaction is an important sensory modality for all avian species