bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurons define non-myelinated axon segments by the regulation of galectin-4-containing axon membrane domains
Authors: Díez-Revuelta Natalia , Higuero Alonso M. , Velasco Silvia , Peñas-de-la-Iglesia María , Gabius Hans-Joachim , Abad-Rodríguez José
Published: March 2017

The mechanism underlying selective myelination of axons versus dendrites or neuronal somata relies on the expression of somatodendritic membrane myelination inhibitors (i.e. JAM2). However, axons still present long unmyelinated segments proposed to contribute to axonal plasticity and higher order brain functions. Why these segments remain unmyelinated is still an unresolved issue. The bifunctional lectin galectin-4 (Gal-4) organizes the transport of axon glycoproteins by binding to N-acetyllactosamine (LacNac) termini of N-glycans. We have shown that Gal-4 is sorted to segmental domains (G4Ds) along the axon surface, reminiscent of these long unmyelinated axon segments in cortical neurons. We report here that oligodendrocytes (OLGs) do not deposit myelin on Gal-4 covered surfaces or myelinate axonal G4Ds. In addition, Gal-4 interacts and co-localizes in G4Ds with contactin-1, a marker of non-myelinated nodes of Ranvier. Neither Gal-4 expression nor G4D dimensions are affected by myelin extracts or myelinating OLGs, but are reduced with neuron maturation. As in vitro, Gal-4 is consistently segregated from myelinated structures in the brain. Our data shape the novel concept that neurons establish and regulate axon membrane domains expressing Gal-4, the first inhibitor of myelination identified in axons, whose boundaries delineate myelination-incompetent axon segments along neuron development.
Analyzing contentious relationships and outlier genes in phylogenomics
Authors: Walker Joseph F. , Brown Joseph W. , Smith Stephen A.
Published: March 2017

Recent studies have demonstrated that conflict is common among gene trees in phylogenomic studies, and that less than one percent of genes may ultimately drive species tree inference in supermatrix analyses. Here, we examined two datasets where supermatrix and coalescent-based species trees conflict. We identified two highly influential “outlier” genes in each dataset. When removed from each dataset, the inferred supermatrix trees matched the topologies obtained from coalescent analyses. We also demonstrate that, while the outlier genes in the vertebrate dataset have been shown in a previous study to be the result of errors in orthology detection, the outlier genes from a plant dataset did not exhibit any obvious systematic error and therefore may be the result of some biological process yet to be determined. While topological comparisons among a small set of alternate topologies can be helpful in discovering outlier genes, they can be limited in several ways, such as assuming all genes share the same topology. Coalescent species tree methods relax this assumption but do not explicitly facilitate the examination of specific edges. Coalescent methods often also assume that conflict is the result of incomplete lineage sorting (ILS). Here we explored a framework that allows for quickly examining alternative edges and support for large phylogenomic datasets that does not assume a single topology for all genes. For both datasets, these analyses provided detailed results confirming the support for coalescent-based topologies. This framework suggests that we can improve our understanding of the underlying signal in phylogenomic datasets by asking more targeted edge-based questions.
Assessing the chemistry and bioavailability of dissolved organic matter from glaciers and rock glaciers
Authors: Fegel Timothy , Boot Claudia M. , Broeckling Corey D. , Hall Ed K.
Published: March 2017

As glaciers thaw in response to warming, they release dissolved organic matter (DOM) to alpine lakes and streams. The United States contains an abundance of both alpine glaciers and rock glaciers. Differences in DOM composition and bioavailability between glacier types, like rock and ice glaciers, remain undefined. To assess differences in glacier and rock glacier DOM we evaluated bioavailability and molecular composition of DOM from four alpine catchments each with a glacier and a rock glacier at their headwaters. We assessed bioavailability of DOM by incubating each DOM source with a common microbial community and evaluated chemical characteristics of DOM before and after incubation using untargeted gas chromatography mass spectrometry based metabolomics (GC-MS). Prior to incubations, ice glacier and rock glacier DOM had similar C:N ratios and chemical diversity, but differences in DOM composition. Incubations with a common microbial community showed DOM from ice glacier meltwaters contained a higher proportion of bioavailable DOM (BDOM) and resulted in greater bacterial growth efficiency (BGE). After incubation, DOM composition from each source was statistically indistinguishable. This study provides an example of how MS based metabolomics can be used to assess effects of DOM composition on differences in bioavailability of DOM. Furthermore, it illustrates the importance of microbial metabolism in structuring composition of DOM. Even though rock glaciers had significantly less BDOM than ice glaciers, both glacial types still have potential to be important sources of BDOM to alpine headwaters over the coming decades.

Key Points

Bioavailability of organic matter released from glaciers is greater than that of rock glaciers in the Rocky Mountains.

The use of GC-MS for ecosystem metabolomics represents a novel approach for examining complex organic matter pools.

Both glaciers and rock glaciers supply highly bioavailable sources of organic matter to alpine headwaters in Colorado.
Asymmetric evolution of the transcription profiles andcis-regulatory sites contributes to the retention of transcription factor duplicates
Authors: Panchy Nicholas L. , Azodi Christina B. , Winship Eamon F. , O’Malley Ronan C. , Shiu Shin-Han
Published: March 2017

Transcription factors (TFs) play a key role in regulating plant development and response to environmental stimuli. While most genes revert to single copy after a duplication event, transcription factors are retained at a significantly higher rate. However, it is unclear why TF duplicates have higher rates of retention relative to other genes. In this study, we compared three types of features (expression, sequence, and conservation) of retained TFs following whole genome duplication (WGD) events to genes with other functions, usingArabidopsis thalianaas a model. We found that gene function groups with higher maximum expression but lower mean expression tended to have higher duplicate retention rate post WGD, though TFs in particular are retained more often than would be expected based on the features examined. Conversely, expression of individual genes was not associated with duplication, but sequence conservation was. Furthermore, we found that the evolution of TF expression patterns and cis-regulatory cites favors the partitioning of ancestral states among the resulting duplicates. In particular, we found that one duplicate retains the majority of ancestral expression and cis-regulatory sites, while the “non-ancestral” duplicate was enriched for novel regulatory sites. To investigate how this pattern of partitioning pattern evolved, we modeled the retention of ancestral states in duplicate pairs using a system of differential equations. Our findings indicate that duplicate pairs evolve to a partitioned state more often than away from it, which in combination with accumulation of new regulatory sites in non-ancestral duplicates, suggest that selection favors partitioning via neofunctionalization.

Author Summary

Gene expression is controlled by regulatory proteins known as transcription factors. These factors control how an organism develops and responds to its environment. The evolution of transcription factor functions also contributes to the emergence of new species and crop domestication. In plants, new transcription factors mainly arise due to polyploidy, multiplication of the genome. Although most duplicated copies are lost following a genome duplication event, transcription factors are exceptional because they are often kept. Furthermore, we found that transcription factor duplicates that tend to diverge in how they are expressed and regulated in an unusual way where one copy mirrors the original, pre-duplication functional states of the ancestral gene, while the other loses the ancestral status and instead accumulates novel regulatory sites. Our results suggest these duplicate transcription factors may have been kept because one copy preserve ancestral function while the other has evolved new ones.
Uncovering Robust Patterns of MicroRNA Co-Expression across Cancers Using Bayesian Relevance Networks
Authors: Ramachandran Parameswaran , Sánchez-Taltavull Daniel , Perkins Theodore J.
Published: March 2017

Co-expression networks have long been used as a tool for investigating the molecular circuitry governing biological systems. However, most algorithms for constructing co-expression networks were developed in the microarray era, before high-throughput sequencing—with its unique statistical properties—became the norm for expression measurement. Here we develop Bayesian Relevance Networks, an algorithm that uses Bayesian reasoning about expression levels to account for the differing levels of uncertainty in expression measurements between highly- and lowly-expressed entities, and between samples with different sequencing depths. It combines data from groups of samples (e.g., replicates) to estimate group expression levels and confidence ranges. It then computes uncertainty-moderated estimates of cross-group correlations between entities, and uses permutation testing to assess their statistical significance. Using large scale miRNA data from The Cancer Genome Atlas, we show that our Bayesian update of the classical Relevance Networks algorithm provides improved reproducibility in co-expression estimates and lower false discovery rates in the resulting co-expression networks. Software is available atwww.perkinslab.ca/Software.html.
Morphological Alternations of Intraepithelial and Stromal Telocytes in Response to Salinity Challenges
Authors: Abdel-latief Soliman Soha Mohamed , Ali Emeish Walaa Fathy
Published: March 2017

Summary statement

The article represent an experimental study in which we investigated the effect of the ssalinty on the communicating cells (telocytes) and their target cells including chloride, stem, Rodlet cells, myoblasts

Telocyte is a communicating cell established relations to various types of cells. Few experimental studies are performed on telocytes. The current study investigated responce of telocytes to salinity stress in relations to osmoregualtory, immune and stem cells. We exposed Common carp to salinity level 0.2, 6, 10, 14 ppt. Gill samples were fixed and processed for microscopic and TEM. Two types of telocytes were identified: intraepithelial and stromal telocytes. Intraepithelial telocytes comprised the cellular lining of the lymph spaces where they shed the secretory vesicles. Stromal telocytes shed their secretory vesicles in the secondary circulatory vessels. Telocyte enlarged and exhibited high secretory activities. They exert their effect either by direct contact or by paracrine mode. In sanity treated samples, chloride cells enlarged and the mitochondria became cigar-shaped. pavement cells enlarged and micro-ridges elongated. Stromal telocytes established contact with stem cell and skeletal myoblast. Macrophages and Rodlet cells increased in number. In conclusion, intraepithelial and stromal responded to salinity stress by activation of cellular signaling. They play a major role in osmoregulation, immunity, and regeneration.
Identification and characterization of m6A circular RNA epitranscriptomes
Authors: Zhou Chan , Molinie Benoit , Daneshvar Kaveh , Pondick Joshua V. , Wang Jinkai , Van Wittenberghe Nicholas O. , Xing Yi , Giallourakis Cosmas C. , Mullen Alan C.
Published: March 2017

This study brings together the expanding fields of RNA modifications and circular (circ) RNAs. We find that cells express thousands of m6A methylated circRNAs, with cell-type specificity observed between human embryonic stem cells and HeLa cells. m6A-circRNAs were identified by RNA sequencing of total RNA following ribosome depletion and m6A immunoprecipitation. The presence of m6A-circRNAs is corroborated by the identification of complexes between circRNAs and YTHDF1 and YTHDF2, proteins that “read” m6A sites in mRNAs.

Furthermore, m6A modifications on non-linear RNAs depend on METTL3 and METTL14, the known m6A methyltransferase “writer” complex components, suggesting that circRNAs are methylated by the same complexes responsible for m6A modification of linear RNAs. Despite sharing m6A readers and writers, m6A-circRNAs are frequently derived from exons not methylated in mRNAs. Nevertheless, m6A-mRNAs that are methylated on the same exons as those composing m6A-circRNAs exhibit less stability than other m6A-mRNA, and this circRNA-mRNA cross-talk is regulated by YTHDF2. Thus, our results expand the m6A regulatory code through identification of the first circRNA epitranscriptome.
Presynaptic LRP4 Promotes Synapse Number and Function of Excitatory CNS Neurons
Authors: Mosca Timothy J. , Luginbuhl David J. , Wang Irving E. , Luo Liqun
Published: March 2017

Precise coordination of synaptic connections ensures proper information flow within circuits. The activity of presynaptic organizing molecules signaling to downstream pathways is essential for such coordination, though such entities remain incompletely known. We show that LRP4, a conserved transmembrane protein known for its postsynaptic roles, functions presynaptically as an organizing molecule. In theDrosophilabrain, LRP4 preferentially localizes to excitatory neuron terminals at or near active zones. Loss of presynaptic LRP4 reduces excitatory (not inhibitory) synapse number, impairs active zone architecture, and abolishes olfactory attraction - the latter of which can be suppressed by reducing presynaptic GABABreceptors. LRP4 overexpression increases synapse number in excitatory and inhibitory neurons, suggesting an instructive role and a common downstream synapse addition pathway. Mechanistically, LRP4 functions via the conserved kinase SRPK79D to ensure normal synapse number and behavior. This highlights a presynaptic function for LRP4, enabling deeper understanding of how synapse organization is coordinated.
Developing Gene-Specific Meta-Predictor of Variant Pathogenicity
Authors: Rychkova Anna , Buu MyMy C. , Scharfe Curt , Lefterova Martina I. , Odegaard Justin I. , Schrijver Iris , Milla Carlos , Bustamante Carlos D.
Published: March 2017

Rapid, accurate, and inexpensive genome sequencing promises to transform medical care. However, a critical hurdle to enabling personalized genomic medicine is predicting the functional impact of novel genomic variation. Various methods of missense variants pathogenicity prediction have been developed by now. Here we present a new strategy for developing a pathogenicity predictor of improved accuracy by applying and training a supervised machine learning model in a gene-specific manner. Our meta-predictor combines outputs of various existing predictors, supplements them with an extended set of stability and structural features of the protein, as well as its physicochemical properties, and adds information about allele frequency from various datasets. We used such a supervised gene-specific meta-predictor approach to train the model on theCFTRgene, and to predict pathogenicity of about 1,000 variants of unknown significance that we collected from various publicly available and internal resources. OurCFTR-specific meta-predictor based on the Random Forest model performs better than other machine learning algorithms that we tested, and also outperforms other available tools, such as CADD, MutPred, SIFT, and PolyPhen-2. Our predicted pathogenicity probability correlates well with clinical measures of Cystic Fibrosis patients and experimental functional measures of mutated CFTR proteins. Training the model on one gene, in contrast to taking a genome wide approach, allows taking into account structural features specific for a particular protein, thus increasing the overall accuracy of the predictor. Collecting data from several separate resources, on the other hand, allows to accumulate allele frequency information, estimated as the most important feature by our approach, for a larger set of variants. Finally, our predictor will be hosted on the ClinGen Consortium database to make it available to CF researchers and to serve as a feasibility pilot study for other Mendelian diseases.
CaMK (CMK-1) and O-GlcNAc transferase (OGT-1) modulate mechanosensory responding and habituation in an interstimulus interval-dependent manner inCaenorhabditis elegans
Authors: Ardiel Evan L. , McDiarmid Troy A. , Timbers Tiffany A. , Lee Kirsten C. Y. , Safaei Javad , Pelech Steven L. , Rankin Catharine H.
Published: March 2017

The ability to learn is an evolutionarily conserved adaptation that remains incompletely understood. Genetically tractable model organisms facilitate mechanistic explanations of learning that span genetic, neural circuit, and behavioural levels. Many aspects of neural physiology, including processes that underlie learning (e.g.neurotransmitter release and long-lasting changes in synaptic strength), are regulated by brief and local changes in [μm] levels of free intracellular Ca2+. On this scale, changes in [Ca2+] activate many Ca2+-sensors, including the Ca2+/calmodulin-dependent kinases (CaMKs). Here we reveal that theCaenorhabditis elegansortholog of CaMK1/4, CMK-1, functions in primary sensory neurons to regulate responses to mechanical stimuli and behavioral plasticity, specifically habituation, a conserved form of non-associative learning. The habituation phenotypes ofcmk-1mutants were dependent on interstimulus interval (ISI), such that CMK-1 slows habituation at short ISIs, but promotes it at long ISIs. We predicted potential CaMK phosphorylation targets from catalytic site analysis of the human andC. elegansCaMKs and mutant analysis of these candidates implicated O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, in mechanosensitivity and learning. Cell specific rescue and knockdown experiments showed that both CMK-1 and OGT-1 function cell autonomously in mechanosensory neurons to modulate learning. Interestingly, despite their similar mutant phenotypes, detailed behavioral analysis of double mutants demonstrated that CMK-1 and OGT-1 act in parallel genetic pathways. Our research identifies CMK-1 and OGT-1 as co-expressed yet independent regulators of mechanosensitivity and learning.
Novel de novo variant in EBF3 is likely to impact DNA binding in a patient with a neurodevelopmental disorder and expanded phenotypes: patient report, in silico functional assessment, and review of published cases
Authors: Blackburn Patrick R. , Barnett Sarah S. , Zimmermann Michael T. , Cousin Margot A. , Kaiwar Charu , Pinto e Vairo Filippo , Niu Zhiyv , Ferber Matthew J. , Urrutia Raul A. , Selcen Duygu , Klee Eric W. , Pichurin Pavel N.
Published: March 2017

Pathogenic variants in EBF3 were recently described in three back-to-back publications in association with a novel neurodevelopmental disorder characterized by intellectual disability, speech delay, ataxia, and facial dysmorphisms. In this report, we describe an additional patient carrying a de novo missense variant in EBF3 (c.487C>T, p.(Arg163Trp)) that falls within a conserved residue in the zinc knuckle motif of the DNA binding domain. Without a solved structure of the DNA binding domain, we generated a homology-based atomic model and performed molecular dynamics simulations for EBF3, which predicted decreased DNA affinity for p.(Arg163Trp) compared with wild-type protein and control variants. These data are in agreement with previous experimental studies of EBF1 showing the paralogous residue is essential for DNA binding. The conservation and experimental evidence existing for EBF1 and in silico modeling and dynamics simulations to validate comparable behavior of multiple variants in EBF3 demonstrates strong support for the pathogenicity of p.(Arg163Trp). We show that our patient presents with phenotypes consistent with previously reported patients harboring EBF3 variants and expands the phenotypic spectrum of this newly identified disorder with the additional feature of a bicornuate uterus.
Serum soluble interleukin‐2 receptor level is more sensitive than angiotensin‐converting enzyme or lysozyme for diagnosis of sarcoidosis and may be a marker of multiple organ involvement
Authors: Thi Hong Nguyen Chuyen , Kambe Naotomo , Kishimoto Izumi , Ueda‐Hayakawa Ikuko , Okamoto Hiroyuki
Published: March 2017

Skin lesions in sarcoidosis are often the initial symptoms that enable the dermatologist to be the first to diagnose this granulomatosis. However, diagnosis is sometimes very problematic. In 2015, the diagnostic criteria for sarcoidosis were updated in Japan, with elevated serum soluble interleukin‐2 receptor (sIL‐2R) replacing negative tuberculin reaction. Therefore, we assessed the clinical utility of sIL‐2R compared with two other common markers, angiotensin‐converting enzyme (ACE) and lysozyme, in patients who visited the dermatology clinic. Data from 72 patients showed that sIL‐2R was more sensitive than both ACE and lysozyme in supporting a diagnosis of sarcoidosis (52.8%) compared with ACE (29%) and lysozyme (26.4%). Additionally, the sIL‐2R level was significantly higher in patients with multiple organ involvement and parenchymal infiltration. Patients with elevated sIL‐2R levels had higher serum ACE and lysozyme levels, a higher incidence of pulmonary involvement, more severe chest radiographic stage and a high incidence of expression‐specific signs by imaging analysis. Receiver–operator curve analysis showed that sIL‐2R was a better marker at the threshold cut‐off point compared with ACE and lysozyme for identifying patients with multiple organ involvement, detecting patients with pulmonary disease and parenchymal infiltration as well as predicting the presence of specific signs in the diagnosis of sarcoidosis. Moreover, the kinetics of sIL‐2R levels correlated closely with clinical manifestations, in contrast to the modest changes of ACE and lysozyme levels during the follow‐up period. In conclusion, sIL‐2R may be considered a good marker for diagnosis and a potential indicator of disease activity.
Concomitant confluent and reticulated papillomatosis and acanthosis nigricans in an obese girl with insulin resistance successfully treated with oral minocycline: Case report and published work review
Authors: Fukumoto Takeshi , Kozaru Takeshi , Sakaguchi Masanobu , Oka Masahiro
Published: March 2017

Concomitant confluent and reticulated papillomatosis (CRP) and acanthosis nigricans (AN) is rare. We present a case of concomitant CRP and obesity‐associated AN in a 12‐year‐old obese Japanese girl. Curiously, oral minocycline therapy, which has been shown to be effective for CRP, was effective against both CRP and AN. Possible mechanisms by which minocycline could have improved skin lesions of CRP and obesity‐associated AN are discussed. In addition, reports of concomitant CRP and obesity‐associated AN are reviewed. CRP and obesity‐associated AN share common clinicopathological features and some reports have described concomitant CRP and obesity‐associated AN. Together with the observation that skin lesions of CRP and obesity‐associated AN in the present case responded to oral minocycline therapy, these facts suggest a tight relationship or a common pathogenetic pathway between these pathologies.
Two cases of melanomas paradoxically metastasizing to the intestinal tract during nivolumab therapy
Authors: Miyazawa Hajime , Yanagi Teruki , Yamaguchi Yasuyuki , Imafuku Keisuke , Kitamura Shinya , Hata Hiroo , Uehara Jiro , Ichikawa Nobuki , Ohno Yosuke , Yoshida Tadashi , Homma Shigenori , Kawamura Hideki , Taketomi Akinobu , Shimizu Hiroshi
Published: March 2017

We report two cases of melanomas in patients who developed intestinal metastasis despite other metastatic sites responding to nivolumab and despite the patients having favorable findings such as vitiligo and normal lactate dehydrogenase. The first case is an 85‐year‐old man who had been administrated nivolumab for lung/cutaneous metastases. After 22 courses of nivolumab therapy, fever and anorexia had appeared and his bodyweight had decreased. An intussusception on the ileocecal valve was revealed by computed tomography, and emergency surgery revealed metastatic lesions on the colon. The second case is an 87‐year‐old woman treated with nivolumab for lymph node metastases. After 10 courses, laboratory tests had revealed anemia and positive fecal occult blood. Her bodyweight had decreased. Capsule endoscopy showed scattered tumors and clots, indicating metastases of melanoma. The frequency of symptomatic intestinal metastasis of melanoma is very low. Further, intestinal metastasis of melanoma is difficult to detect through routine examinations. Our cases suggest that fecal occult blood test and decreased bodyweight are indications of intestinal metastases.
Evaluation of positron emission tomography imaging to detect lymph node metastases in patients with extramammary Paget's disease
Authors: Fujiwara Masao , Suzuki Takahiro , Senoo Ayumi , Fukamizu Hidekazu , Tokura Yoshiki
Published: March 2017

Patients with extramammary Paget's disease (EMPD) have a relatively good prognosis, when spread of the tumor cells is limited to the epidermis. However, invasive EMPD has a poor prognosis, when the patients have regional lymph node metastasis. Detection of nodal metastasis is thus mandatory to manage EMPD. To evaluate the 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) imaging to assess lymph node metastasis, 15 patients with histologically proven primary EMPD were enrolled in this study. All patients underwent whole‐body PET prior to sentinel lymph node biopsy (SLNB). The maximum standardized uptake value (SUVmax) of more than 2.5 was evaluated as positive PET indicative of malignancy. Among 14 cases with the primary genital lesions, 11 cases underwent bilateral SLNB of the inguinal nodal basin and the remaining three cases unilateral SLNB. One case with a primary axillary lesion underwent unilateral SLNB of the axillary nodal basin. Therefore, a total of 26 regional basins were investigated. In general, nodal basins can be categorized into four groups: (i) histologically negative and PET negative (true negative); (ii) histologically positive and PET negative (false negative); (iii) histologically positive and PET positive (true positive); and (iv) histologically negative and PET positive (false positive) groups. In the 26 nodal basins, there were 19 true negative and seven true positive cases, and neither false negative nor false positive cases were observed. The mean SUVmax was significantly higher in the true positive basins (8.03 ± 3.34) than in the true negative basins (0.26 ± 0.56). The SUVmax value may be useful for detection of nodal metastasis.
Peripartum type B aortic dissection in patients with Marfan syndrome who underwent aortic root replacement: a case series study
Authors: Sayama S , Takeda N , Iriyama T , Inuzuka R , Maemura S , Fujita D , Yamauchi H , Nawata K , Bougaki M , Hyodo H , Shitara R , Nakayama T , Komatsu A , Nagamatsu T , Osuga Y , Fujii T
Published: March 2017

Objective

To investigate pregnancy outcomes, especially the risk of pregnancy‐related aortic dissection (AD), in patients with Marfan syndrome (MFS) after prophylactic aortic root replacement (ARR).

Design

Retrospective case series study.

Setting

Tertiary perinatal care centre at a university hospital.

Population

Pregnant women fulfilling the revised Ghent nosology (2010) criteria for MFS who were managed at our institute.

Methods

The pregnancy outcomes of all patients with MFS managed at our institute between 1982 and September 2016 were reviewed retrospectively based on medical records.

Main outcome measures

Obstetrical management and complication including the incidence of AD throughout the peripartum period.

Results

Among 22 patients (28 pregnancies) who had been managed as potential MFS or related disorders, 14 (17 pregnancies) fulfilled the revised Ghent nosology (2010) criteria for MFS and were enrolled in this study. Five patients (five pregnancies) had received ARR before conception: three (60%) developed type B aortic dissection [AD(B)] during the peripartum period, compared with only one of 10 patients (12 pregnancies) without ARR (P < 0.05, Chi‐square test).

Conclusions

Our study results suggest that MFS patients after prophylactic ARR are still at high risk of AD(B) during the peripartum period. Careful pre‐pregnancy counselling and multidisciplinary care throughout the peripartum period are essential for the management of MFS, even after surgical repair of an ascending aortic aneurysm.

Tweetable abstract

MFS patients after prophylactic ARR are still at high risk of type B aortic dissection during the peripartum period.
Exploiting a readily available but hard to digest resource: A review of exudativorous mammals identified thus far and how they cope in captivity
Authors: CABANA Francis , DIERENFELD Ellen S. , Wirdateti  , DONATI Giuseppe , NEKARIS K. A. I.
Published: March 2017

Gum is a widely available carbohydrate, composed mainly of non‐digestible structural carbohydrates. No mammalian enzymes can digest gum; therefore, a mammal ingesting gum must rely on microbial fermentation to access the energy it possesses. Gums are relatively nutrient poor. Despite this, some mammals have evolved to exploit this food resource. We aim to review the literature for all mammal species which have been recorded to ingest gum, whether quantified or not, and discuss this in the context of their evolutionary adaptations. We also investigated the recommended captive diets for these species to look at whether gum is recommended. We conducted a literature search on ISI Web of Knowledge to tabulate all mammal species observed ingesting gum and classified them as obligate, facultative or opportunistic feeders. We encountered 94 mammal species that eat gum in the wild (27 obligate feeders, 34 facultative feeders and 33 opportunistic feeders). Obligate feeders have entirely evolved to exploit this resource but were found to not be given gum in captivity, which may explain why they are failing to thrive, as opposed to facultative feeders, which have fewer issues. Gum may be necessary for the health of obligate feeders in captivity. Future research should focus on the physiological effects that gum ingestion poses on different digestive systems.
The Relevance to Investors of Greenhouse Gas Emission Disclosures
Authors: Griffin Paul A. , Lont David H. , Sun Estelle Y.
Published: March 2017

This study finds that investors price firms' greenhouse gas (GHG) emissions as a negative component of equity value, and this valuation discount does not differ between firms that voluntarily disclose to the Carbon Disclosure Project (CDP) and nondisclosing firms. We derive the GHG emissions for nondisclosers from an estimation model that incorporates firm characteristics and industry. The finding that investors view CDP amounts and estimates of emissions as equally value‐relevant suggests that equity values reflect GHG information from channels other than the CDP. An event study of investors' response to emission‐related information in firms' 8‐K filings further supports this finding. Economically, our results suggest that, for the median S&P 500 firm, GHG emissions impose a market‐implied equity discount of $79 per ton, representing about one‐half of 1 percent of market capitalization.
The statistical need to include phylogeny in trait‐based analyses of community composition
Authors: Li Daijiang , Ives Anthony R.
Published: March 2017

A growing number of studies incorporate functional trait information to analyse patterns and processes of community assembly. These studies of trait–environment relationships generally ignore phylogenetic relationships among species. When functional traits and the residual variation in species distributions among communities have phylogenetic signal, however, analyses ignoring phylogenetic relationships can decrease estimation accuracy and power, inflate type I error rates and lead to potentially false conclusions.

Using simulations, we compared estimation accuracy, statistical power and type I error rates of linear mixed models (LMM) and phylogenetic linear mixed models (PLMM) designed to test for trait–environment interactions in the distribution of species abundances among sites. We considered the consequences of both phylogenetic signal in traits and phylogenetic signal in the residual variation in species distributions generated by an unmeasured (latent) trait with phylogenetic signal.

When there was phylogenetic signal in the residual variation in species among sites, PLMM provided better estimates (closer to the true value) and greater statistical power for testing whether the trait–environment interaction regression coefficient differed from zero. LMM had unacceptably high type I error rates when there was phylogenetic signal in both traits and the residual variation in species distributions. When there was no phylogenetic signal in the residual variation in species distributions, LMM and PLMM had similar performances.

Linear mixed models that ignore phylogenetic relationships can lead to poor statistical tests of trait–environment relationships when there is phylogenetic signal in the residual variation in species distributions among sites, such as caused by unmeasured traits. Therefore, phylogenies and PLMMs should be used when studying how functional traits affect species abundances among communities in response to environmental gradients.
The application of statistical network models in disease research
Authors: Silk Matthew J. , Croft Darren P. , Delahay Richard J. , Hodgson David J. , Weber Nicola , Boots Mike , McDonald Robbie A.
Published: March 2017

Host social structure is fundamental to how infections spread and persist, and so the statistical modelling of static and dynamic social networks provides an invaluable tool to parameterise realistic epidemiological models.

We present a practical guide to the application of network modelling frameworks for hypothesis testing related to social interactions and epidemiology, illustrating some approaches with worked examples using data from a population of wild European badgers Meles meles naturally infected with bovine tuberculosis.

Different empirical network datasets generate particular statistical issues related to non‐independence and sampling constraints. We therefore discuss the strengths and weaknesses of modelling approaches for different types of network data and for answering different questions relating to disease transmission.

We argue that statistical modelling frameworks designed specifically for network analysis offer great potential in directly relating network structure to infection. They have the potential to be powerful tools in analysing empirical contact data used in epidemiological studies, but remain untested for use in networks of spatio‐temporal associations.

As a result, we argue that developments in the statistical analysis of empirical contact data are critical given the ready availability of dynamic network data from bio‐logging studies. Furthermore, we encourage improved integration of statistical network approaches into epidemiological research to facilitate the generation of novel modelling frameworks and help extend our understanding of disease transmission in natural populations.
The Association of Electrocardiographic Abnormalities and Acute Coronary Syndrome in Emergency Patients With Chest Pain
Authors: Knowlman Thomas , Greenslade Jaimi H. , Parsonage William , Hawkins Tracey , Ruane Lorcan , Martin Paul , Prasad Sandhir , Lancini Daniel , Cullen Louise
Published: March 2017

Objectives

The electrocardiograph (ECG) is an essential tool in initial management and risk stratification of patients with suspected acute coronary syndrome (ACS). A six‐point reporting criterion has been proposed to facilitate standardized clinical assessment of patients presenting to the emergency department (ED) with suspected ACS. We set out to evaluate the efficacy of these criteria in identifying patients with major adverse cardiac events (MACE), Type 1 myocardial infarction (T1MI), Type 2 myocardial infarction (T2MI), and 1‐year mortality in a cohort of emergency patients with chest pain.

Methods

This was an analysis of data from 2,349 patients who presented to the ED with chest pain between 2008 and 2013. Data were collected as part of two prospective trials. ECGs were recorded at presentation and categorized according to the six‐point criteria by local cardiologists blinded to all clinical information. The primary outcome was 30‐day MACE, including T1MI, T2MI, unstable angina pectoris, revascularization, and 30‐day mortality. The outcome was adjudicated by cardiologists on the basis of all clinical information and test results. Likelihood ratios and odds ratios for 30‐day MACE were reported for each ECG category.

Results

Major adverse cardiac events were diagnosed in 264 (11.3%) patients. Increasing ischemic abnormalities in ECGs, as categorized by the standardized reporting criteria, were associated with increasing rates of MACE. Within 30 days, T1MI occurred in 148 (6.3%) patients and T2MI occurred in 59 (2.5%) patients. Risk for T1MI increased with higher classification of ECG abnormalities. T2MI rates were highest in patients with ECGs of nonspecific changes.

Conclusions

The rates of MACE, T1MI, and 1‐year death can be stratified according to standardized ECG criteria in patients presenting to the ED with chest pain. The ECG findings in patients with T2MI are variable, and the ECG is less helpful in defining risk in this group.
Validating Harmful Alcohol Use as a Phenotype for Genetic Discovery Using Phosphatidylethanol and a Polymorphism in ADH1B
Authors: Justice Amy C. , McGinnis Kathleen A. , Tate Janet P. , Xu Ke , Becker William C. , Zhao Hongyu , Gelernter Joel , Kranzler Henry R.
Published: March 2017

Background

Although alcohol risk is heritable, few genetic risk variants have been identified. Longitudinal electronic health record (EHR) data offer a largely untapped source of phenotypic information for genetic studies, but EHR‐derived phenotypes for harmful alcohol exposure have yet to be validated. Using a variant of known effect, we used EHR data to develop and validate a phenotype for harmful alcohol exposure that can be used to identify unknown genetic variants in large samples. Herein, we consider the validity of 3 approaches using the 3‐item Alcohol Use Disorders Identification Test consumption measure (AUDIT‐C) as a phenotype for harmful alcohol exposure.

Methods

First, using longitudinal AUDIT‐C data from the Veterans Aging Cohort Biomarker Study Cohort (VACS‐BC), we compared 3 metrics of AUDIT‐C using correlation coefficients: (i) AUDIT‐C closest to blood sampling (closest AUDIT‐C), (ii) the highest value (highest AUDIT‐C), (iii) and longitudinal trajectories generated using joint trajectory modeling (AUDIT‐C trajectory). Second, we compared the associations of the 3 AUDIT‐C metrics with phosphatidylethanol (PEth), a direct, quantitative biomarker for alcohol in the overall sample using chi‐square tests for trend. Last, in the subsample of African Americans (AAs; n = 1,503), we compared the associations of the 3 AUDIT‐C metrics with rs2066702 a common missense (Arg369Cys) polymorphism of the ADH1B gene, which encodes an alcohol dehydrogenase isozyme.

Results

The sample (n = 1,851, 94.5% male, 65% HIV+, mean age 52 years) had a median of 7 AUDIT‐C scores over a median of 6.1 years. Highest AUDIT‐C and AUDIT‐C trajectory were correlated r = 0.86. The closest AUDIT‐C was obtained a median of 2.26 years after the VACS‐BC blood draw. Overall and among AAs, all 3 AUDIT‐C metrics were associated with PEth (all p < 0.05), but the gradient was steepest with AUDIT‐C trajectory. Among AAs (36% with the protective ADH1B allele), the association of rs2066702 with AUDIT‐C trajectory and highest AUDIT‐C was statistically significant (p < 0.05), and the gradient was steeper for the AUDIT‐C trajectory than for the highest AUDIT‐C. The closest AUDIT‐C was not statistically significantly associated with rs2066702.

Conclusions

EHR data can be used to identify complex phenotypes such as harmful alcohol use. The validity of the phenotype may be enhanced through the use of longitudinal trajectories.
Designing seed mixtures for restoration on alpine soils: who should your neighbours be?
Authors: Rydgren Knut , Hagen Dagmar , Rosef Line , Pedersen Bård , Aradottir Asa L.
Published: March 2017

Questions

(1) When alpine vegetation is actively restored by seeding, how is vegetation cover influenced by seeding treatments and soil conditions? (2) How does the cover of species differ when they are seeded in a mixture and how is their response influenced by soil conditions? (3) Do individual species perform better or worse in a mixture than when sown separately?

Location

Hjerkinn, Dovrefjell, Norway.

Methods

In a factorial, randomized field experiment, we recorded the percentage cover of Festuca ovina, Luzula multiflora subsp. frigida and Poa alpina seeded in four different soil types for 3 yr after seeding. We seeded the three species separately and in a mixture in organic topsoil, peat soil, mineral fine soil and mineral coarse soil. We also recorded seedling emergence in a greenhouse experiment, using the same seeding treatments.

Results

In the field experiment, vegetation cover established fastest when F. ovina was sown in monoculture, followed by the seed mixture. After 3 yr, mean cover of F. ovina was 1.4 times higher than mean P. alpina cover and more than three times higher than mean L. multiflora cover for single species treatments, and four (P. alpina) and 15 (L. multiflora) times higher when the species were seeded together. L. multiflora germinated slowly in the greenhouse experiment, which could partly explain its poor field performance. In the field experiment, establishment was faster in organic soils than mineral soils for all seeding treatments. The largest difference between F. ovina and L. multiflora performance in the mixture treatment was found in the organic soil types, where overall cover was larger than in the mineral soils. In the organic soils, F. ovina was slightly facilitated in the mixture treatment, while the opposite was found for L. multiflora.

Conclusion

When the restoration goal is to quickly establish a vegetation cover, seeding monocultures of rapidly establishing species may be more effective than seeding mixtures, even in alpine sites, where interspecific facilitation may prevail.
Experiment‐based recommendations for biodiversity‐friendly management of mountain hay meadows
Authors: Lessard‐Therrien Malie , Humbert Jean‐Yves , Arlettaz Raphaël
Published: March 2017

Question

The biodiversity of mountain hay meadows has historically been maintained through traditional, low‐intensity farming practices. In recent decades, however, agricultural intensification for hay production has led to dramatic declines in their biodiversity. This study asks: which management practices can contribute to maintaining the biodiversity value of mountain hay meadows without jeopardizing agricultural revenue?

Location

Eleven semi‐natural meadows, canton of Valais, inner Alps, southwest Switzerland.

Methods

We experimentally measured the effects of various intensities of fertilization (slurry) and aerial irrigation (sprinklers) on the taxonomic, phylogenetic and functional diversity of plants. The experiment consisted of six different treatments, each randomly applied to one of six plots within a meadow. A plot therefore was (1) not irrigated and only fertilized with slurry, (2) not fertilized and only irrigated with a sprinkler, (3–5) receiving low, medium or high amounts of both fertilizer and water, respectively, or (6) receiving no input of irrigation or fertilizer (control plots).

Results

After 4 yr, all biodiversity metrics were negatively impacted under the highest management intensity (irrigation combined with fertilization at concentrations corresponding to the input necessary to achieve maximum local hay yield, i.e. three‐thirds of inputs). In contrast, at low‐ and mid‐intensity management levels (irrigation combined with fertilization at one‐third and two‐thirds of the maximum concentration, respectively) most diversity metrics did not differ from the controls, except for forb species richness, which was already reduced under mid‐intensity management compared to low‐intensity and control plots. Neither irrigation nor fertilization alone had a negative impact on plant biodiversity.

Conclusions

Low to moderate agricultural intensification of hay production does not appear to be detrimental to plant biodiversity among mountain meadows. These results suggest that sustainable management would be obtained via irrigation and fertilization corresponding to one‐third to two‐thirds of the quantity necessary to achieve maximum local hay yield.
Use of oral antidiabetic agents and risk of community‐acquired pneumonia: a nested case–control study
Authors: Gorricho Javier , Garjón Javier , Alonso Alvaro , Celaya María Concepción , Saiz Luis Carlos , Erviti Juan , López Antonio
Published: March 2017

Aims

To evaluate the association between use of different oral antidiabetic agents (OAD) and the risk of community‐acquired pneumonia (CAP) in patients with type‐2 diabetes (T2DM).

Methods

Case–control study nested in a cohort of patients with T2DM and use of OAD between 2002 and 2013, based in a Spanish general practice research database. Cases were people diagnosed with T2DM, aged >18 years and with a validated diagnosis of CAP between 2002 and 2013. Ten controls were matched on age, sex and calendar year. Odds ratio (OR) of CAP was estimated comparing patients treated with: (1) metformin vs. other monotherapies or no antidiabetic treatment; (2) metformin + sulfonylureas vs. other antidiabetic combinations. OR of CAP was also assessed according to antidiabetic treatment duration.

Results

From a cohort of 76 009 T2DM patients, we identified 1803 cases of CAP. No difference in the incidence of CAP was observed when comparing any OAD in monotherapy with metformin. Compared with current use of metformin + sulfonylurea, thiazolidinediones + metformin was associated with an increased risk of CAP (adjusted OR = 2.48, 95% CI 1.40–4.38). The use of any combination with thiazolidinediones was also associated with higher risk of CAP (adjusted OR = 2.00, 95% CI 1.22–3.28). Current use of DPP‐4 inhibitors was not associated with an increased risk of CAP.

Conclusions

No differences in the incidence of CAP were observed between the use of OAD in monotherapy vs. metformin. Thiazolidinedione use in combination was associated with an increase in the risk of CAP when compared to metformin + sulfonylureas. The use of DPP‐4 inhibitors was not associated with an increased risk of CAP.