bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring evolutionary relationships across the genome using topology weighting
Authors: Martin Simon H. , Van Belleghem Steven M.
Published: August 2016

We introduce the concept of topology weighting, a method for quantifying relationships between taxa that are not necessarily monophyletic, and visualising how these relationships change across the genome. A given set of taxa can be related in a limited number of ways, but if each taxon is represented by multiple sequences, the number of possible topologies becomes very large. Topology weighting reduces this complexity by quantifying the contribution of each ‘taxon topology’ to the full tree. We describe our method for topology weighting by iterative sampling of sub-trees (Twisst), and test it on both simulated and real genomic data. Overall, we show that this is an informative and versatile approach, suitable for exploring relationships in almost any genomic dataset.

Scripts to implement the method described are available atgithub.com/simonhmartin/twisst.
iELVis: An open source MATLAB toolbox for localizing and visualizing human intracranial electrode data
Authors: Groppe David M. , Bickel Stephan , Dykstra Andrew R. , Wang Xiuyuan , Mégevand Pierre , Mercier Manuel R. , Lado Fred A. , Mehta Ashesh D. , Honey Christopher J.
Published: August 2016

Background

Intracranial electrical recordings (iEEG) and brain stimulation (iEBS) are invaluable human neuroscience methodologies. However, the value of such data is often unrealized as many laboratories lack tools for localizing electrodes relative to anatomy. To remedy this, we have developed a MATLAB toolbox for intracranial electrode localization and visualization, iELVis.

New Method

iELVis uses existing tools (BioImage Suite, FSL, and FreeSurfer) for preimplant magnetic resonance imaging (MRI) segmentation, neuroimaging coregistration, and manual identification of electrodes in postimplant neuroimaging.

Subsequently, iELVis implements methods for correcting electrode locations for postimplant brain shift with millimeter-scale accuracy and provides interactive visualization on 3D surfaces or in 2D slices with optional functional neuroimaging overlays. iELVis also localizes electrodes relative to FreeSurfer-based atlases and can combine data across subjects via the FreeSurfer average brain.

Results

It takes 30-60 minutes of user time and 12-24 hours of computer time to localize and visualize electrodes from one brain. We demonstrate iELVis’s functionality by showing that three methods for mapping primary hand somatosensory cortex (iEEG, iEBS, and functional MRI) provide highly concordant results.

Comparison with Existing Methods

iELVis is the first public software for electrode localization that corrects for brain shift, maps electrodes to an average brain, and supports neuroimaging overlays. Moreover, its interactive visualizations are powerful and its tutorial material is extensive.

Conclusions

iELVis promises to speed the progress and enhance the robustness of intracranial electrode research. The software and extensive tutorial materials are freely available as part of the EpiSurg software project:https://github.com/episurg/episurg
Biotinylation by antibody recognition - A novel method for proximity labeling
Authors: Bar Daniel Z , Atkatsh Kathleen , Tavarez Urraca , Erdos Michael R , Gruenbaum Yosef , Collins Francis S
Published: August 2016

Identification of protein-protein interactions is a major goal of biological research. Despite technical advances over the last two decades, important but still largely unsolved challenges include the high-throughput detection of interactions directly from primary tissue and the identification of interactors of insoluble proteins that form higher-order structures. We have developed a novel, proximity-based labeling approach that uses antibodies to guide biotin deposition onto adjacent proteins in fixed cells and primary tissues. We used this method to profile the dynamic interactome of lamin A/C in multiple cell and tissue types under various treatment conditions. Our results suggest a considerable variation in the composition of the nuclear envelope of different tissues. Of note, DNA damage response proteins Ku70 and Ku80 are more abundant in the vicinity of lamin A/C after thermal stress. This increased affinity also applies to the progerin isoform, potentially contributing to the premature aging phenotype of Hutchinson-Gilford progeria syndrome. The ability to detect protein-protein interactions in intact tissues, and to compare affinities quantitatively under different conditions or in the presence of disease mutations, can provide a new window into cell biology and disease pathogenesis.
FUN-LDA: A LATENT DIRICHLET ALLOCATION MODEL FOR PREDICTING TISSUE-SPECIFIC FUNCTIONAL EFFECTS OF NONCODING VARIATION
Authors: Backenroth Daniel , He Zihuai , Kiryluk Krzysztof , Boeva Valentina , Pethukova Lynn , Khurana Ekta , Christiano Angela , Buxbaum Joseph D. , Ionita-Laza Iuliana
Published: August 2016

ABSTRACT

We describe here a new method based on a latent Dirichlet allocation model for predicting functional effects of noncoding genetic variants in a cell type and tissue specific way (FUN-LDA) by integrating diverse epigenetic annotations for specific cell types and tissues from large scale epige-nomics projects such as ENCODE and Roadmap Epigenomics. Using this unsupervised approach we predict tissue-specific functional effects for every position in the human genome. We demonstrate the usefulness of our predictions using several validation experiments. Using eQTL data from several sources, including the Genotype-Tissue Expression project, the Geuvadis project and Twin-sUK cohort, we show that eQTLs in specific tissues tend to be most enriched among the predicted functional variants in relevant tissues in Roadmap. We further show how these integrated functional scores can be used to derive the most likely cell/tissue type causally implicated for a complex trait using summary statistics from genome-wide association studies, and estimate a tissue-based correlation matrix of various complex traits. We find large enrichment of heritability in functional components of relevant tissues for various complex traits, with FUN-LDA yielding the highest enrichment estimates relative to existing methods. Finally, using experimentally validated functional variants from the literature and variants possibly implicated in disease by previous studies, we rigorously compare FUN-LDA to state-of-the-art functional annotation methods such as GenoSky-line, ChromHMM, Segway, and IDEAS, and show that FUN-LDA has better prediction accuracy and higher resolution compared to these methods. In summary, we describe a new approach and perform rigorous comparisons with the most commonly used functional annotation methods, providing a valuable resource for the community interested in the functional annotation of noncoding variants. Scores for each position in the human genome and for each ENCODE/Roadmap tissue are available fromhttp://www.columbia.edu/~ii2135/funlda.html.
Neuronal firing rates diverge during REM and homogenize during non-REM
Authors: Miyawaki Hiroyuki , Watson Brendon , Diba Kamran
Published: August 2016

Neurons fire at highly variable innate rates and recent evidence suggests that low and high firing rate neurons display different plasticity and dynamics. Furthermore, recent publications imply possibly differing rate-dependent effects in hippocampus versus neocortex, but those analyses were carried out separately and with possibly important differences. To more effectively synthesize these questions, we analyzed the firing rate dynamics of populations of neurons in both hippocampal CA1 and frontal cortex under one framework that avoids pitfalls of previous analyses and accounts for regression-to-the-mean. We observed remarkably consistent effects across these regions. While rapid eye movement (REM) sleep was marked by decreased hippocampal firing and increased neocortical firing, in both regions firing rates distributions widened during REM due to differential changes in high-firing versus low-firing cells in parallel with increased interneuron activity. In contrast, upon non-REM (NREM) sleep, firing rate distributions narrowed while interneuron firing decreased. Interestingly, hippocampal interneuron activity closely followed the patterns observed in neocortical principal cells rather than the hippocampal principal cells, suggestive of long-range interactions. Following these undulations in variance, the net effect of sleep was a decrease in firing rates. These decreases were greater in lower-firing hippocampal neurons but higher-firing frontal cortical neurons, suggestive of greater plasticity in these cell groups. Our results across two different regions and with statistical corrections indicate that the hippocampus and neocortex show a mixture of differences and similarities as they cycle between sleep states with a unifying characteristic of homogenization of firing during NREM and diversification during REM.

Significance Statement

Miyawaki and colleagues analyze firing patterns across low-firing and high-firing neurons in the hippocampus and the frontal cortex throughout sleep in a framework that accounts for regression-to-the-mean. They find that in both regions REM sleep activity is relatively dominated by high-firing neurons and increased inhibition, resulting in a wider distribution of firing rates. On the other hand, NREM sleep produces lower inhibition, and results in a more homogenous distribution of firing rates. Integration of these changes across sleep results in net decrease of firing rates with largest drops in low-firing hippocampal pyramidal neurons and high-firing neocortical principal neurons. These findings provide insights into the effects and functions of different sleep stages on cortical neurons.
Inferring Fitness Landscapes and Selection on Phenotypic States from Single-Cell Genealogical Data
Authors: Nozoe Takashi , Kussell Edo , Wakamoto Yuichi
Published: August 2016

Recent advances in single-cell time-lapse microscopy have revealed non-genetic heterogeneity and temporal fluctuations of cellular phenotypes. While different phenotypic traits such as abundance of growth-related proteins in single cells may have differential effects on the reproductive success of cells, rigorous experimental quantification of this process has remained elusive due to the complexity of single cell physiology within the context of a proliferating population. We introduce and apply a practical empirical method to quantify the fitness landscapes of arbitrary phenotypic traits, using genealogical data in the form of population lineage trees which can include phenotypic data of various kinds. Our inference methodology for fitness landscapes determines how reproductivity is correlated to cellular phenotypes, and provides a natural generalization of bulk growth rate measures for single-cell histories. Using this technique, we quantify the strength of selection acting on different cellular phenotypic traits within populations, which allows us to determine whether a change in population growth is caused by individual cells’ response, selection within a population, or by a mixture of these two processes. By applying these methods to single-cell time-lapse data of growing bacterial populations that express a resistance-conferring protein under antibiotic stress, we show how the distributions, fitness landscapes, and selection strength of single-cell phenotypes are affected by the drug. Our work provides a unified and practical framework for quantitative measurements of fitness landscapes and selection strength for any statistical quantities definable on lineages, and thus elucidates the adaptive significance of phenotypic states in time series data. The method is applicable in diverse fields, from single cell biology to stem cell differentiation and viral evolution.
Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells
Authors: Guo Jessie Yanxiang , Teng Xin , Laddha Saurabh V. , Ma Sirui , Van Nostrand Stephen C. , Yang Yang , Khor Sinan , Chan Chang S. , Rabinowitz Joshua D. , White Eileen
Published: August 2016

Autophagy degrades and is thought to recycle proteins, other macromolecules, and organelles. In genetically engineered mouse models (GEMMs) for Kras-driven lung cancer, autophagy prevents the accumulation of defective mitochondria and promotes malignancy. Autophagy-deficient tumor-derived cell lines are respiration-impaired and starvation-sensitive. However, to what extent their sensitivity to starvation arises from defective mitochondria or an impaired supply of metabolic substrates remains unclear. Here, we sequenced the mitochondrial genomes of wild-type or autophagy-deficient (Atg7−/−) Kras-driven lung tumors. Although Atg7 deletion resulted in increased mitochondrial mutations, there were too few nonsynonymous mutations to cause generalized mitochondrial dysfunction. In contrast, pulse-chase studies with isotope-labeled nutrients revealed impaired mitochondrial substrate supply during starvation of the autophagy-deficient cells. This was associated with increased reactive oxygen species (ROS), lower energy charge, and a dramatic drop in total nucleotide pools. While starvation survival of the autophagy-deficient cells was not rescued by the general antioxidant N-acetyl-cysteine, it was fully rescued by glutamine or glutamate (both amino acids that feed the TCA cycle and nucleotide synthesis) or nucleosides. Thus, maintenance of nucleotide pools is a critical challenge for starving Kras-driven tumor cells. By providing bioenergetic and biosynthetic substrates, autophagy supports nucleotide pools and thereby starvation survival.
Inhibition of microRNA 128 promotes excitability of cultured cortical neuronal networks
Authors: McSweeney K. Melodi , Gussow Ayal B. , Bradrick Shelton S. , Dugger Sarah A. , Gelfman Sahar , Wang Quanli , Petrovski Slavé , Frankel Wayne N. , Boland Michael J. , Goldstein David B.
Published: August 2016

Cultured neuronal networks monitored with microelectrode arrays (MEAs) have been used widely to evaluate pharmaceutical compounds for potential neurotoxic effects. A newer application of MEAs has been in the development of in vitro models of neurological disease. Here, we directly evaluated the utility of MEAs to recapitulate in vivo phenotypes of mature microRNA-128 (miR-128) deficiency, which causes fatal seizures in mice. We show that inhibition of miR-128 results in significantly increased neuronal activity in cultured neuronal networks derived from primary mouse cortical neurons. These results support the utility of MEAs in developing in vitro models of neuroexcitability disorders, such as epilepsy, and further suggest that MEAs provide an effective tool for the rapid identification of microRNAs that promote seizures when dysregulated.
Chromatin dynamics during DNA replication
Authors: Bar-Ziv Raz , Voichek Yoav , Barkai Naama
Published: August 2016

Chromatin is composed of DNA and histones, which provide a unified platform for regulating DNA-related processes, mostly through their post-translational modification. During DNA replication, histone arrangement is perturbed, first to allow progression of DNA polymerase and then during repackaging of the replicated DNA. To study how DNA replication influences the pattern of histone modification, we followed the cell-cycle dynamics of 10 histone marks in budding yeast. We find that histones deposited on newly replicated DNA are modified at different rates: While some marks appear immediately upon replication (e.g., H4K16ac, H3K4me1), others increase with transcription-dependent delays (e.g., H3K4me3, H3K36me3). Notably, H3K9ac was deposited as a wave preceding the replication fork by ∼5–6 kb. This replication-guided H3K9ac was fully dependent on the acetyltransferase Rtt109, while expression-guided H3K9ac was deposited by Gcn5. Further, topoisomerase depletion intensified H3K9ac in front of the replication fork and in sites where RNA polymerase II was trapped, suggesting supercoiling stresses trigger H3K9 acetylation. Our results assign complementary roles for DNA replication and gene expression in defining the pattern of histone modification.
Coding and noncoding variants in HFM1, MLH3, MSH4, MSH5, RNF212, and RNF212B affect recombination rate in cattle
Authors: Kadri Naveen Kumar , Harland Chad , Faux Pierre , Cambisano Nadine , Karim Latifa , Coppieters Wouter , Fritz Sébastien , Mullaart Erik , Baurain Denis , Boichard Didier , Spelman Richard , Charlier Carole , Georges Michel , Druet Tom
Published: August 2016

We herein study genetic recombination in three cattle populations from France, New Zealand, and the Netherlands. We identify 2,395,177 crossover (CO) events in 94,516 male gametes, and 579,996 CO events in 25,332 female gametes. The average number of COs was found to be larger in males (23.3) than in females (21.4). The heritability of global recombination rate (GRR) was estimated at 0.13 in males and 0.08 in females, with a genetic correlation of 0.66 indicating that shared variants are influencing GRR in both sexes. A genome-wide association study identified seven quantitative trait loci (QTL) for GRR. Fine-mapping following sequence-based imputation in 14,401 animals pinpointed likely causative coding (5) and noncoding (1) variants in genes known to be involved in meiotic recombination (HFM1, MSH4, RNF212, MLH3, MSH5) for 5/7 QTL, and noncoding variants (3) in RNF212B for 1/7 QTL. This suggests that this RNF212 paralog might also be involved in recombination. Most of the identified mutations had significant effects in both sexes, with three of them each accounting for ∼10% of the genetic variance in males.
The Chloroplast Protease AMOS1/EGY1 Affects Phosphate Homeostasis under Phosphate Stress
Authors: Yu Fang Wei , Zhu Xiao Fang , Li Guang Jie , Kronzucker Herbert J. , Shi Wei Ming
Published: August 2016

Plastid intramembrane proteases in Arabidopsis (Arabidopsis thaliana) are involved in jasmonic acid biosynthesis, chloroplast development, and flower morphology. Here, we show that Ammonium-Overly-Sensitive1 (AMOS1), a member of the family of plastid intramembrane proteases, plays an important role in the maintenance of phosphate (P) homeostasis under P stress. Loss of function of AMOS1 revealed a striking resistance to P starvation. amos1 plants displayed retarded root growth and reduced P accumulation in the root compared to wild type (Col-0) under P-replete control conditions, but remained largely unaffected by P starvation, displaying comparable P accumulation and root and shoot growth under P-deficient conditions. Further analysis revealed that, under P-deficient conditions, the cell wall, especially the pectin fraction of amos1, released more P than that of wild type, accompanied by a reduction of the abscisic acid (ABA) level and an increase in ethylene production. By using an ABA-insensitive mutant, abi4, and applying ABA and ACC exogenously, we found that ABA inhibits cell wall P remobilization while ethylene facilitates P remobilization from the cell wall by increasing the pectin concentration, suggesting ABA can counteract the effect of ethylene. Furthermore, the elevated ABA level and the lower ethylene production also correlated well with the mimicked P deficiency in amos1. Thus, our study uncovers the role of AMOS1 in the maintenance of P homeostasis through ABA-antagonized ethylene signaling.
Crystal structure of dimethylformamidium bis(trifluoromethanesulfonyl)amide: an ionic liquid
Authors: Cardenas Allan Jay P. , O'Hagan Molly
Published: August 2016

At 100 K, the title molecular salt, C3H8NO+·C2F6NO4S2
−, has orthorhombic (P212121) symmetry; the amino H atom of bis(trifluoromethanesulfonyl)amine (HNTf2) was transferred to the basic O atom of dimethylformamide (DMF) when the ionic liquid components were mixed. The structure displays an O—H...N hydrogen bond, which links the cation to the anion, which is reinforced by a non-conventional C—H...O interaction, generating an R
2
2(7) loop. A further very weak C—H...O interaction generates an [001] chain.
(Z)-3-Allyl-5-(4-fluorobenzylidene)-2-sulfanylidenethiazolidin-4-one
Authors: El Ajlaoui Rahhal , Belkhouya Najat , Rakib El Mostapha , Mojahidi Souad , Saadi Mohamed , El Ammari Lahcen
Published: August 2016

In the title compound, C13H10FNOS2, the sulfanylidenethiazolidine ring and the benzylidene ring are almost coplanar [dihedral angle between the two planes = 0.1 (2)°]. The mean plane through the allyl group is nearly perpendicular to the sulfanylidenethiazolidine ring, as indicated by the dihedral angle of 69.5 (5)° between them. In the crystal, molecules are linked together by weak C—H...O hydrogen bonds involving the same acceptor atom, forming dimers parallel to (1-22).
4-Chloro-N-(isoquinolin-3-yl)butanamide
Authors: Loganathan C. , Ananad S. Athavan Alias , Alphonsa A. Therasa , Kabilan S. , Selvanayagam S.
Published: August 2016

All C, N and O atoms of the title compound, C13H13ClN2O, lie in a common plane (r.m.s. deviation = 0.096 Å). The Cl atom deviates by 0.940 (3) Å from this plane. In the crystal, molecules are linkedviaN—H...N and C—H...O hydrogen bonds which formR22(8) andR22(16) graph-set dimers. In addition, molecules are linkedviaC—H...O intermolecular interactions which formC(4) chains propagating along the [100] direction of the unit cell.
Synergistic antitumor effect of a human papillomavirus DNA vaccine harboring E6E7 fusion gene and vascular endothelial growth factor receptor 2 gene
Authors: Gao Jie , Fan Lei , Ma Wei , Xiao Huan
Published: August 2016

Human papillomavirus (HPV) has been identified as the primary etiological factor in cervical cancer as well as in subsets of anogenital and oropharyngeal cancers. The two HPV viral oncoproteins, E6 and E7, are uniquely and consistently expressed in all HPV‐infected cells and are therefore promising targets for therapeutic vaccination. In order to achieve a synergistic antitumor and anti‐angiogenesis effect, we designed and constructed a novel DNA vaccine that can express the HPV 16 E6E7 fusion protein and VEGFR2 in the same reading frame. A series of DNA plasmids encoding E6E7, VEGFR2 and their conjugates were constructed and injected into mice. The resultant humoral and cellular immune responses were detected by ELISA and enzyme‐linked immunospot (ELISPOT), respectively. To evaluate the antitumor efficacy of these plasmids, tumor‐bearing mice expressing the E6E7 fusion protein were constructed. After injection into the tumor‐bearing mouse model, the plasmid harboring the E6E7 fusion gene and VEGFR2 showed stronger inhibition of tumor growth than the plasmid expressing E6E7 or VEGFR2 alone, which indicated that the combination of E6E7 and VEGFR2 could exert a synergistic antitumor effect. These observations emphasize the potential of a synergistic antitumor and anti‐angiogenesis strategy using a DNA vaccine, which could be a promising approach for tumor immunotherapy.
NOAA Radios and Neighbourhood Networks: Demographic Factors for Channel Preference for Hurricane Evacuation Information
Authors: DeYoung Sarah E. , Wachtendorf Tricia , Farmer Ashley K. , Penta Samantha C.
Published: August 2016

This paper reviews literature on information channel type and disasters, and presents results on hurricane evacuation information gathering. Results show that respondents reported they would use television and radio most frequently for gathering information about hurricane evacuation. Minority respondents reported more preference of the use of community or local government as information sources than white respondents, females gathered information from multiple channels more than males, and younger residents gathered information from multiple channels more than older respondents. Implications include areas for future research in how channel utilization occurs during slow onset hazards in predominantly black communities, how age and gender relate to channel preference, and how channel preferences affect length of time to make decisions and engage in protective actions.
Sample Dimensionality Effects on d′ and Proportion of Correct Responses in Discrimination Testing
Authors: Bloom David J. , Lee Soo‐Yeun
Published: August 2016

Products in the food and beverage industry have varying levels of dimensionality ranging from pure water to multicomponent food products, which can modify sensory perception and possibly influence discrimination testing results. The objectives of the study were to determine the impact of (1) sample dimensionality and (2) complex formulation changes on the d′ and proportion of correct response of the 3‐AFC and triangle methods. Two experiments were conducted using 47 prescreened subjects who performed either triangle or 3‐AFC test procedures. In Experiment I, subjects performed 3‐AFC and triangle tests using model solutions with different levels of dimensionality. Samples increased in dimensionality from 1‐dimensional sucrose in water solution to 3‐dimensional sucrose, citric acid, and flavor in water solution. In Experiment II, subjects performed 3‐AFC and triangle tests using 3‐dimensional solutions. Sample pairs differed in all 3 dimensions simultaneously to represent complex formulation changes. Two forms of complexity were compared: dilution, where all dimensions decreased in the same ratio, and compensation, where a dimension was increased to compensate for a reduction in another. The proportion of correct responses decreased for both methods when the dimensionality was increased from 1‐ to 2‐dimensional samples. No reduction in correct responses was observed from 2‐ to 3‐dimensional samples. No significant differences in d′ were demonstrated between the 2 methods when samples with complex formulation changes were tested. Results reveal an impact on proportion of correct responses due to sample dimensionality and should be explored further using a wide range of sample formulations.
Microwave‐Assisted Extraction, Chemical Structures, and Chain Conformation of Polysaccharides from a Novel Cordyceps Sinensis Fungus UM01
Authors: Cheong Kit‐Leong , Wang Lan‐Ying , Wu Ding‐Tao , Hu De‐Jun , Zhao Jing , Li Shao‐Ping
Published: August 2016

Cordyceps sinensis is a well‐known tonic food with broad medicinal properties. The aim of the present study was to investigate the optimization of microwave‐assisted extraction (MAE) and characterize chemical structures and chain conformation of polysaccharides from a novel C. sinensis fungus UM01. Ion‐exchange and gel filtration chromatography were used to purify the polysaccharides. The chemical structure of purified polysaccharide was determined through gas chromatography‐mass spectrometry. Moreover, high performance size exclusion chromatography combined with refractive index detector and multiangle laser light scattering were conducted to analyze the molecular weight (Mw) and chain conformation of purified polysaccharide. Based on the orthogonal design L9, optimal MAE conditions could be obtained through 1300 W of microwave power, with a 5‐min irradiation time at a solid to water ratio of 1:60, generating the highest extraction yield of 6.20%. Subsequently, the polysaccharide UM01‐S1 was purified. The UM01‐S1 is a glucan‐type polysaccharide with a (1→4)‐β‐d‐glucosyl backbone and branching points located at O‐3 of Glcp with a terminal‐d‐Glcp. The Mw, radius of gyration (Rg) and hydrodynamic radius (Rh) of UM01‐S1 were determined as 5.442 × 106 Da, 21.8 and 20.2 nm, respectively. Using the polymer solution theory, the exponent (ν) value of the power law function was calculated as 0.38, and the shape factor (ρ = Rg/Rh) was 1.079, indicating that UM01‐S1 has a sphere‐like conformation with a branched structure in an aqueous solution. These results provide fundamental information for the future application of polysaccharides from cultured C. sinensis in health and functional food area.
Exploring divergent antibiotic resistance genes in ancient metagenomes and discovery of a novel beta‐lactamase family
Authors: Rascovan Nicolás , Telke Amar , Raoult Didier , Rolain Jean Marc , Desnues Christelle
Published: August 2016

Antibiotic resistance in pathogenic bacteria is a major problem for human health. We analyzed metagenomic datasets from ancient and remote samples from diverse environmental sources and observed the presence of all the eleven antibiotic resistance genes (ARG) groups evaluated. Since ancient samples are not subjected to modern effects of antibiotic misuse, they represent a clean model to explore the natural diversity of ARG in the environment. Most sequences showed high divergence compared with known ARG, representing a much larger universe than the currently known and characterized ARGs. We explored whether proteins within the “divergent resistome” may correspond to functional ARG by characterizing a beta‐lactamase hit with very low similarity to any known sequence (<45% to best BLAST hit in NCBI). By starting from purely in‐silico data, we revived a new family of class B beta‐lactamases from ancient medieval samples, which exhibited a very high penicillinase activity. In this work, we explored ancient resistomes and added novel support to previous works showing that the universe of ARG is naturally vast and diverse in microbial communities. Our results bring a new perspective to the exploration of environmental ARG and indicate that this gigantic reservoir represents a natural endless source of emerging resistances.
Childhood cognitive ability and smoking initiation, relapse and cessation throughout adulthood: evidence from two British cohort studies
Authors: Daly Michael , Egan Mark
Published: August 2016

Aims

To test the relationship between early cognitive ability and major changes in smoking habits across adulthood, and test whether educational attainment mediates these associations.

Design

Prospective observational study to examine the link between cognitive ability and smoking initiation, relapse and cessation at multiple time‐points throughout adulthood in a pooled analysis of two cohorts.

Setting

Great Britain 1981–2013.

Participants

A total of 16 653 participants from two British cohorts; 7191 from the 1970 British Cohort Study (BCS) and 9462 from the 1958 National Child Development Study (NCDS). Participants were 52.9% female and 27.3% were smokers, 24.8% were ex‐smokers and 47.9% reported never smoking.

Measurements

Cognitive ability was assessed at age 10 years in the BCS and 11 years in the NCDS. Outcomes were smoking initiation, relapse and cessation derived from changes in smoking status observed across five time‐points between ages 26–42 in the BCS and six time‐points between ages 23–55 in the NCDS. Educational attainment was examined as a mediating variable. Controls were age, gender, social class, self‐control, psychological distress, parental smoking and a study indicator (BCS/NCDS).

Findings

In adjusted regression models, a 1 standard deviation increase in cognitive ability predicted a 0.5 percentage point (95% CI = −0.9 to −0.1) reduced probability of smoking and a 2.9 percentage point (95% CI = 2.1–3.7) higher probability of smoking cessation throughout adulthood, but did not change the likelihood of smoking relapse significantly. Differences in educational attainment explained approximately half the association between childhood cognitive ability and smoking initiation/cessation.

Conclusions

Lower cognitive ability, measured in childhood before smoking is initiated, appears to predict a higher likelihood of taking up smoking and a lower likelihood of quitting in adulthood. Educational attainment appears to mediate this effect: children with higher cognitive ability tend to become more highly educated adults which, in turn, predicts lower rates of smoking initiation and increased rates of smoking cessation.
Trajectories of cannabis use disorder: risk factors, clinical characteristics and outcomes
Authors: Kosty Derek B. , Seeley John R. , Farmer Richard F. , Stevens Joseph J. , Lewinsohn Peter M.
Published: August 2016

Aims

To estimate cannabis use disorder (CUD) trajectory classes from ages 14 to 30 years and compare classes on clinical characteristics, risk factors and psychosocial outcomes.

Design

Four waves (T1–T4) of data from an epidemiological study of psychopathology among a regionally representative sample. Trajectory classes described risk for CUD as a function of age. The number of classes was determined by model fit.

Setting

Participants were selected randomly from nine high schools in western Oregon, USA.

Participants

The sample included 816 participants [age at T1 mean = 16.6, standard deviation (SD) = 1.2; 44% male; 8% non‐white].

Measurements

Participants completed diagnostic interviews, Child Trauma Questionnaire, Social Adjustment Scale and items adapted from the Wisconsin Manual for Assessing Psychotic‐Like Experiences.

Findings

There were three CUD trajectory classes (Lo–Mendell–Rubin likelihood ratio test < 0.001): (1) persistent increasing risk; (2) maturing out, with increasing risk then decreasing risk; and (3) stable low risk. The persistent increasing class had later initial CUD onsets (η2 = 0.16, P < 0.001) and greater cumulative CUD durations (η2 = 0.26, P < 0.001). Male sex [odds ratio (OR) = 2.57, P = 0.018], externalizing disorders between ages 24 and 30 years (OR = 2.64, P < 0.001) and psychotic experiences during early adulthood (Cohen's d = 0.44, P = 0.016) discriminated between the persistent increasing and the maturing‐out classes.

Conclusions

Evidence suggests three distinguishable types of trajectory for development of cannabis use disorder starting in early teens: (1) persistent increasing risk; (2) maturing out, with increasing risk then decreasing risk; and (3) stable low risk.
Effects of the insecticides methoxyfenozide and cypermethrin on non‐target arthropods: a field experiment
Authors: Loetti Verónica , Bellocq Isabel
Published: August 2016

The adverse effect of pesticides on non‐target organisms and the environment is an issue of great social concern. Currently, there are a variety of availably insecticides, which are claimed to be safer for beneficial organisms than broad‐spectrum insecticides. We conducted a field experiment to compare the effect of applications of methoxyfenozide (an insect growth regulator) and cypermethrin (a conventional insecticide) on the arthropod community in a commercial willow plantation. We used a one‐way Anova design with insecticide as the treatment factor, each individual tree as the experimental unit, and the number of dead arthropods collected per sampling unit as the response variable. Results showed that the number of dead arthropods collected 72 h after treatment with methoxyfenozide (1274 individuals) was 66% lower than that collected underneath cypermethrin‐treated trees (3408 individuals). The only groups not recorded from boxes places underneath methoxyfenozide‐treated trees, but yes underneath cypermethrin‐treated trees, were Dyctioptera, Pseudoscorpionida and Isopoda. Methoxyfenozide was lethal to a lower number of families of dipterans, coleopterans and hymenopterans than the cypermethrin during the first 72 h after treatment. The number of taxonomic groups and abundance of dead predators, herbivores and parasitoids was also lower in methoxyfenozide than in cypermethrin‐treated trees. Our results obtained from a field experiment suggest that methoxyfenozide provides a less toxic alternative for control of pests in willow plantations due to a reduced effect on non‐target organisms.
Prospective population‐based cohort study of maternal obesity as a source of error in gestational age estimation at 11–14 weeks
Authors: Bak Geske S. , Sperling Lene , Källén Karin , Salvesen Kjell Å.
Published: August 2016

Introduction

An impact of maternal obesity on ultrasound dating of pregnancy at 11–14 gestational weeks is possible and was investigated.

Material and methods

A prospective cohort study based on the Danish national population during a 4‐year period in which we entered all mothers with singleton pregnancies who had a known last menstrual period (LMP), a recorded booking of body mass index (BMI), and a late first trimester ultrasound dating scan using crown‐rump‐length measurement (gestational age 11+0–13+6 weeks). Almost all scans were performed transabdominally. Transvaginal ultrasound was only performed in the case of limited visibility by transabdominal scanning. Differences between LMP and ultrasound estimated date of delivery (EDD) were stratified by BMI classes. Odds ratios (ORs) were calculated and adjusted for maternal age, parity and smoking.

Results

In total, 187 486 women were analyzed: 21.8% were overweight and 12.3% obese. Ultrasound EDD was ≥7 days later than by LMP in 5.8% of normal‐weight women, 7.3% of obese women, and 10.0% of women with morbid obesity. Compared with normal BMI (18.5–24.9), the OR for postponing EDD increased with increasing BMI; BMI 25–29.9 [OR 0.97, 95% confidence interval (CI) 0.93–1.02], BMI 30–34.9 (OR 1.14, 95% CI 1.07–1.23), BMI 35–39.9 (OR 1.28, 95% CI 1.15–1.42), and BMI 40+ (OR 1.73, 95% CI 1.50–1.98). Lean pregnant women (BMI <18.5) also had a higher chance of having EDD postponed 7 days or more (OR 1.11, 95% CI 1.01–1.22).

Conclusion

Rising maternal BMI appears to be associated with postponement of ultrasound EDD.
Reduced physical exercise and health‐related quality of life after Fontan palliation
Authors: Hedlund Eva R. , Lundell Bo , Villard Li , Sjöberg Gunnar
Published: August 2016

Aim

A growing number of patients with Fontan circulation are reaching adulthood, and there is increasing concern about their physical performance and quality of life. This study compared self‐reported exercise and measured activity with quality of life in patients after Fontan palliation and healthy controls.

Methods

Physical exercise during an average school week was reported by 30 Fontan circulation patients aged eight to 20 years, and 25 healthy controls, followed by accelerometer recordings over seven days. All subjects and their parents answered a questionnaire on quality of life.

Results

Patients reported spending less time exercising each week than the controls (114 ± 66 minutes vs. 228 ± 147 minutes, p < 0.001). However, the overall measured activity and moderate‐to‐vigorous activity was similar for patients and controls. Patients reported a lower quality of life score than the controls (70.9 ± 9.9 vs. 85.7 ± 8.0, p < 0.001).

Conclusion

In spite of similar measured total activity, Fontan patients reported less time engaged in regular physical exercise than healthy controls and their quality of life was lower than the controls. We speculate that promoting structured regular physical exercise could improve the quality of life of Fontan patients.
Prophylactic Melatonin Attenuates Isoflurane‐Induced Cognitive Impairment in Aged Rats through Hippocampal Melatonin Receptor 2 – cAMP Response Element Binding Signalling
Authors: Liu Yajie , Ni Cheng , Li Zhengqian , Yang Ning , Zhou Yang , Rong Xiaoying , Qian Min , Chui Dehua , Guo Xiangyang
Published: August 2016

Melatonin exerts many physiological effects via melatonin receptors, among which the melatonin‐2 receptor (MT2) plays a critical role in circadian rhythm disorders, Alzheimer's disease and other neurological disorders. A melatonin replacement strategy has been tested previously, and MT2 was a critical target during the process. cAMP response element binding (CREB) is an essential transcription factor for memory formation and could be involved in MT2 signalling. Therefore, the present study was designed to investigate the effects of prophylactic melatonin on inhaled anaesthetic isoflurane‐induced cognitive impairment, and to determine whether the protective effects of melatonin are dependent on MT2 and downstream CREB signalling in the hippocampus of aged rats. The results showed that prophylactic melatonin attenuated isoflurane‐induced decreases in plasma/hippocampal melatonin levels and cognitive impairment in aged rats. Furthermore, 4P‐PDOT, a selective MT2 antagonist, blocked the protective effects of melatonin on isoflurane‐induced decreases in both hippocampal MT2 expression and downstream CREB phosphorylation. And 4P‐PDOT blocked the attenuation of melatonin on isoflurane‐induced memory impairment. Collectively, the results suggest that the protective effects of prophylactic melatonin are dependent on hippocampal MT2‐CREB signalling, which could be a potential therapeutic target for anaesthetic‐induced cognitive impairment.
Should we use Commitment Contracts to Regulate Student use of Cognitive Enhancing Drugs?
Authors: Danaher John
Published: August 2016

Are universities justified in trying to regulate student use of cognitive enhancing drugs? In this article I argue that they can be, but that the most appropriate kind of regulatory intervention is likely to be voluntary in nature. To be precise, I argue that universities could justifiably adopt a commitment contract system of regulation wherein students are encouraged to voluntarily commit to not using cognitive enhancing drugs (or to using them in a specific way). If they are found to breach that commitment, they should be penalized by, for example, forfeiting a number of marks on their assessments. To defend this model of regulation, I adopt a recently‐proposed evaluative framework for determining the appropriateness of enhancement in specific domains of activity, and I focus on particular existing types of cognitive enhancement drugs, not hypothetical or potential forms. In this way, my argument is tailored to the specific features of university education, and common patterns of usage among students. It is not concerned with the general ethical propriety of using cognitive enhancing drugs.
The mediating role of metacognition in the relationship between executive function and self‐regulated learning
Authors: Follmer D. Jake , Sperling Rayne A.
Published: August 2016

Background

Researchers have demonstrated significant relations among executive function, metacognition, and self‐regulated learning. However, prior research emphasized the use of indirect measures of executive function and did not evaluate how specific executive functions are related to participants’ self‐regulated learning.

Aims

The primary goals of the current study were to examine and test the relations among executive function, metacognition, and self‐regulated learning as well as to examine how self‐regulated learning is informed by executive function.

Sample

The sample comprised 117 undergraduate students attending a large, Mid‐Atlantic research university in the United States.

Methods

Participants were individually administered direct and indirect measures of executive function, metacognition, and self‐regulated learning. A mediation model specifying the relations among the regulatory constructs was proposed.

Results

In multiple linear regression analyses, executive function predicted metacognition and self‐regulated learning. Direct measures of inhibition and shifting accounted for a significant amount of the variance in metacognition and self‐regulated learning beyond an indirect measure of executive functioning. Separate mediation analyses indicated that metacognition mediated the relationship between executive functioning and self‐regulated learning as well as between specific executive functions and self‐regulated learning.

Conclusions

The findings of this study are supported by previous research documenting the relations between executive function and self‐regulated learning, and extend prior research by examining the manner in which executive function and self‐regulated learning are linked. The findings provide initial support for executive functions as key processes, mediated by metacognition, that predict self‐regulated learning. Implications for the contribution of executive functions to self‐regulated learning are discussed.
The effects of caregiver and household HIV on child development: a community‐based longitudinal study of young children
Authors: Sherr L. , Skeen S. , Hensels I. S. , Tomlinson M. , Macedo A.
Published: August 2016

Objective

Many studies that document child outcomes in the context of parental HIV – which has been established as a risk factor for child development – focus on older children/adolescents. Studies also concentrate on the status of the primary caregiver, not other household members who might be infected.

Design

This study examined the effects of caregiver and household HIV on child development (4–13 years) in South Africa and Malawi (2011–2014).

Methods

Data were gathered from 989 children and their primary caregivers at baseline and repeated at 12–15 months follow‐up (86.5% follow‐up rate). Only caregivers of a single child and caregiver/child dyads without missing data were included, providing a sample of 808 dyads for analysis. Children were divided into three groups according to caregiver‐reported HIV burden: having an HIV‐positive primary caregiver (19.8%), having HIV in the household (14.2%) or no HIV (66%).

Results

The HIV burden was positively associated with an array of negative child outcomes, often mediated by caregiver depression levels. Family HIV burden at baseline affected child behavioural problems at follow‐up indirectly through carer depression (B = 0.02; CI = 0.003, 0.06). Internalizing (B = 0.02; CI = 0.002, 0.05) and externalizing problems at follow‐up (B = 0.01; CI = 0.0002, 0.03) were also indirectly affected by family HIV burden through caregiver depression.

Conclusions

The data suggest that family HIV can affect child development, emphasizing the important role of depression in the pathway to such an effect. Community‐based interventions directed at alleviating parental depression in the presence of HIV may help to interrupt the cycle of family HIV and adverse child outcomes.
Traumatic dental injuries and socioeconomic position – findings from the Children's Dental Health Survey 2013
Authors: Blokland Alex , Watt Richard G. , Tsakos Georgios , Heilmann Anja
Published: August 2016

Objectives

The aim of this study was to assess whether traumatic dental injuries (TDI) were socially graded among children and adolescents in England, Wales and Northern Ireland, using nationally representative data from the Children's Dental Health Survey (CDHS) 2013.

Methods

This cross‐sectional study used data from the Children's Dental Health Survey 2013 which was conducted among a nationally representative sample of schoolchildren in England, Wales and Northern Ireland. Children's family socioeconomic position (SEP) was measured through free school meal eligibility and relative area deprivation using the Indices of Multiple Deprivation. The analytical sample included 6707 schoolchildren aged 8, 12 and 15. Multiple logistic regression was used to model the associations between experience of TDI and the two markers of SEP, after adjusting for sex and age.

Results

The overall prevalence of traumatic dental injuries to permanent incisors was 9% (n = 590). There were no statistically significant associations between TDI and either SEP measure. Further subgroup analyses (n = 2650) showed also no significant associations between TDI and additional SEP markers (parental education and social class). The odds of having sustained a traumatic dental injury were higher for boys than for girls and were greater in older age groups.

Conclusions

This study found no significant relationships between the experience of traumatic dental injuries and two markers of family socioeconomic position among children living in England, Wales and Northern Ireland. This implies that rather than specifically targeting the more deprived sectors of society, TDI prevention policies should use upstream public health strategies incorporating a whole‐population approach.