bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro modeling of hyperpigmentation associated to neurofibromatosis type 1 using melanocytes derived from human embryonic stem cells
Authors: Allouche Jennifer , Bellon Nathalia , Saidani Manoubia , Stanchina-Chatrousse Laure , Masson Yolande , Patwardhan Anand , Gilles-Marsens Floriane , Delevoye Cédric , Domingues Sophie , Nissan Xavier , Martinat Cécile , Lemaitre Gilles , Peschanski Marc , Baldeschi Christine
Published: July 2015

Significance

There are few suitable laboratory models for human pigmentation disease. Neurofibromatosis type 1 (NF1) is a common neurocutaneous disease whose initial symptoms in all patients are “café-au-lait” macules and overall skin hyperpigmentation. To analyze the molecular mechanisms associated with this phenotype, we have developed an in vitro model of NF1 based on human embryonic stem cells (hESCs). Melanocytes derived from NF1 hESCs reproduced the hyperpigmentation phenotype in vitro and were characterized by deregulation of melanogenesis factors. The model allowed us to identify the cellular pathways involved in this phenotype. The hyperpigmentation phenotype could be rescued by small molecules, demonstrating the potential of pluripotent stem cells as models for pigmentation disorders.
Optimized deep-targeted proteotranscriptomic profiling reveals unexplored
Conus
toxin diversity and novel cysteine frameworks
Authors: Lavergne Vincent , Harliwong Ivon , Jones Alun , Miller David , Taft Ryan J. , Alewood Paul F.
Published: July 2015

Significance

Venomous marine cone snails have evolved complex mixtures of fast-acting paralytic cysteine-rich peptides for prey capture and defense able to modulate specific heterologous membrane receptors, ion channels, or transporters. In contrast to earlier studies in which the richness and sequence hypervariability of lowly expressed toxins were overlooked, we now describe a comprehensive deep-targeted proteotranscriptomic approach that provides, to our knowledge, the first high-definition snapshot of the toxin arsenal of a venomous animal,
Conus episcopatus
. The thousands of newly identified conotoxins include peptides with cysteine motifs present in FDA-approved molecules or currently undergoing clinical trials. Further highlights include novel cysteine scaffolds likely to unveil unique protein structure and pharmacology, as well as a new category of conotoxins with odd numbers of cysteine residues.
PDGFB-based stem cell gene therapy increases bone strength in the mouse
Authors: Chen Wanqiu , Baylink David J. , Brier-Jones Justin , Neises Amanda , Kiroyan Jason B. , Rundle Charles H. , Lau Kin-Hing William , Zhang Xiao-Bing
Published: July 2015

Significance

Osteoporosis is a morbid disease afflicting millions of people worldwide. To unlock the unique regenerative powers of the skeleton that have not yet been exploited, we used stem cell gene therapy to dramatically increase bone formation at sites where bone is lost during osteoporosis. Our therapy tremendously increased de novo trabecular bone formation and trabecular connections, resulting in a large increase in bone strength. Our therapy has clinical potential, may serve as a prototype for future skeletal stem cell gene therapies, and is a model for mechanistic studies of de novo trabecular bone formation.
New method to compute
R
complete
enables maximum likelihood refinement for small datasets
Authors: Luebben Jens , Gruene Tim
Published: July 2015

Significance

Modern crystallographic structure determination uses maximum likelihood methods. They rely on error estimates between the work model and the unknown target based on a small fraction of the data. This can introduce a large uncertainty and, even worse, restricts the method to projects where sufficient data are available. We investigate the

R

complete

method. It enables the use of all data for error estimation. It reduces the uncertainty associated with the conventional

R

free

approach for small datasets. We show that our approach reduces the effect of overfitting. This enables maximum likelihood methods to be extended to a much wider field of applications, including free electron laser experiments, high-pressure crystallography, and low-resolution structures.
Anomalous scaling law of strength and toughness of cellulose nanopaper
Authors: Zhu Hongli , Zhu Shuze , Jia Zheng , Parvinian Sepideh , Li Yuanyuan , Vaaland Oeyvind , Hu Liangbing , Li Teng
Published: July 2015

Significance

A long-standing challenge in material design is to overcome the conflict between strength and toughness, because they are generally mutually exclusive. To address this challenge, we rationally design cellulose-based nanopaper and investigate the dependence of their mechanical properties on constituent cellulose fiber size. Surprisingly, we find that both the strength and toughness of the nanopaper increase simultaneously (40 and 130 times, respectively) as the average diameter of constituent cellulose fibers decreases from 27 μm to 11 nm, suggesting the promising potential toward an anomalous but highly desirable scaling law: the smaller, the stronger and the tougher. There are abundant opportunities to use the fundamental bottom-up strategy to design a novel class of functional materials that are both strong and tough.
Photodrive of magnetic bubbles via magnetoelastic waves
Authors: Ogawa Naoki , Koshibae Wataru , Beekman Aron Jonathan , Nagaosa Naoto , Kubota Masashi , Kawasaki Masashi , Tokura Yoshinori
Published: July 2015

Significance

In contemporary spintronics, spin transfer torque exerted by a spin-polarized current is often used to control magnetic domains. In addition to it, magnons in both metals and insulators are now regarded as an attractive alternative to deliver and exchange spin momentum with magnetic domain walls. We demonstrate that (
i
) magnetoelastic waves (coupled propagation of phonon and magnon) can be generated in an iron garnet film by ultrafast laser pulses, to be a versatile source of spin momentum, and (
ii
) this traveling spin excitation drives the magnetic domains; more efficiently for those with steeper curvatures at the wall. The latter, the emergent electromagnetic response of the curved domain wall, can be understood by expanding the Thiele equation.
Identification of divergent type VI secretion effectors using a conserved chaperone domain
Authors: Liang Xiaoye , Moore Richard , Wilton Mike , Wong Megan J. Q. , Lam Linh , Dong Tao G.
Published: July 2015

Significance

How different microbial species compete for specific niches is not fully understood. Here, we focus on the type VI secretion system (T6SS), a specialized protein delivery system, which many Gram-negative bacteria use to kill eukaryotic and prokaryotic competitors by translocating toxic protein molecules to target cells. Identification of effectors is required for understanding the pivotal role that the T6SS plays in dictating interbacterial and bacterial–host dynamics. In this study, we describe a new approach to systematically identify T6SS effectors. We also demonstrate that secretion of effectors requires interaction with a set of cognate effector-binding chaperone proteins that we define in this study, providing important insights for understanding the mechanism of T6SS effector delivery.
Vacuolar ATPase depletion affects mitochondrial ATPase function, kinetoplast dependency, and drug sensitivity in trypanosomes
Authors: Baker Nicola , Hamilton Graham , Wilkes Jonathan M. , Hutchinson Sebastian , Barrett Michael P. , Horn David
Published: July 2015

Significance

Anti-trypanosomal drugs, used to tackle lethal human and animal diseases, target an unusual parasite DNA structure in a cellular compartment known as the mitochondrion. Using a high-throughput genetic approach to study drug resistance, we identified every component of a molecular rotor that couples ATP hydrolysis to proton transport across non-mitochondrial membranes. Surprisingly, this molecular machine was found to communicate with a related mitochondrial rotor and, when defective, rendered the mitochondrial DNA structure obsolete. Our findings reveal new potential mechanisms of multidrug resistance in trypanosomes. They also suggest that communication between these rotors in two separate cellular compartments could be conserved through evolution, reflecting an unanticipated and important aspect of environmental sensing and metabolic control in nucleated cells.
Graphene electrostatic microphone and ultrasonic radio
Authors: Zhou Qin , Zheng Jinglin , Onishi Seita , Crommie M. F. , Zettl Alex K.
Published: July 2015

Significance

Humans and other animals effectively use acoustic waves to communicate with each other. Ultrasonic acoustic waves are intriguing because they do not interfere with normal voice communication and can be highly directional with long range. Therefore, wireless ultrasonic radio is a useful communications method. Here we find that graphene has mechanical properties that make it ideally suited for wide-band ultrasonic transduction. Using simple and low-cost fabrication methods we have produced an ultrasonic microphone and ultrasonic radio prototypes. When acting as loudspeaker/microphone alone, the graphene-based acoustic devices also show ideal flat-band frequency response spanning the whole audible region as well as ultrasonic region to at least 0.5 MHz; such flat frequency response has significant acoustic applications implications.
Endoplasmic reticulum stress in the peripheral nervous system is a significant driver of neuropathic pain
Authors: Inceoglu Bora , Bettaieb Ahmed , Trindade da Silva Carlos A. , Lee Kin Sing Stephen , Haj Fawaz G. , Hammock Bruce D.
Published: July 2015

Significance

Here we define the causative role of endoplasmic reticulum (ER) stress on selective modulation of pain signaling. High levels of ER stress and neuropathic pain in diabetic animals are reduced using ER stress blockers. In healthy animals, turning on the ER stress signal transduction cascade generates an immediate but lasting and site restricted painful phenotype, which is reversible by ER stress blockers. This previously unnoticed mechanism explains the broad lack of efficacy of available analgesics and should ignite the discovery of a new generation of therapeutics that do not directly quell ion channel or neurotransmitter activity.
Reanalysis of parabiosis of obesity mutants in the age of leptin
Authors: Zeng Wenwen , Lu Yi-Hsueh , Lee Jonah , Friedman Jeffrey M.
Published: July 2015

Significance

As a central hormone in metabolism, leptin functions to suppress food intake and to dissipate energy. Mutations of leptin or its receptor result in profound obesity. Data from classic parabiosis experiments (a procedure to surgically connect the vascular systems of two mice together) by Douglas Coleman over 40 years ago and recent studies of leptin treatment, have suggested that leptin might require a cofactor to exert its full metabolic strength. However, we found that a leptin-binding protein, clusterin, is dispensable for the normal function of leptin. Rather, the parabiosis procedure itself appears to potentiate the metabolic action of leptin, leading to chronic starvation and lethality of the mice. Our results have resolved a long-standing puzzle in leptin biology.
CCND1–CDK4–mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo
Authors: Mende Nicole , Kuchen Erika E. , Lesche Mathias , Grinenko Tatyana , Kokkaliaris Konstantinos D. , Hanenberg Helmut , Lindemann Dirk , Dahl Andreas , Platz Alexander , Höfer Thomas , Calegari Federico , Waskow Claudia
Published: July 2015

Maintenance of stem cell properties is associated with reduced proliferation. However, in mouse hematopoietic stem cells (HSCs), loss of quiescence results in a wide range of phenotypes, ranging from functional failure to extensive self-renewal. It remains unknown whether the function of human HSCs is controlled by the kinetics of cell cycle progression. Using human HSCs and human progenitor cells (HSPCs), we report here that elevated levels of CCND1–CDK4 complexes promoted the transit from G0 to G1 and shortened the G1 cell cycle phase, resulting in protection from differentiation-inducing signals in vitro and increasing human leukocyte engraftment in vivo. Further, CCND1–CDK4 overexpression conferred a competitive advantage without impacting HSPC numbers. In contrast, accelerated cell cycle progression mediated by elevated levels of CCNE1–CDK2 led to the loss of functional HSPCs in vivo. Collectively, these data suggest that the transition kinetics through the early cell cycle phases are key regulators of human HSPC function and important for lifelong hematopoiesis.
Human Capital and Industrialization: Evidence from the Age of Enlightenment *
Authors: Squicciarini Mara P. , Voigtländer Nico
Published: July 2015

While human capital is a strong predictor of economic development today, its importance for the Industrial Revolution has typically been assessed as minor. To resolve this puzzling contrast, we differentiate average human capital (literacy) from upper-tail knowledge. As a proxy for the historical presence of knowledge elites, we use city-level subscriptions to the famous Encyclopédie in mid-18th century France. We show that subscriber density is a strong predictor of city growth after the onset of French industrialization. Alternative measures of development such as soldier height, disposable income, and industrial activity confirm this pattern. Initial literacy levels, on the other hand, are associated with development in the cross-section, but they do not predict growth. Finally, by joining data on British patents with a large French firm survey from the 1840s, we shed light on the mechanism: upper-tail knowledge raised productivity in innovative industrial technology.
A New Postharvest Fruit Rot in Apple and Pear Caused by Phacidium lacerum
Authors: Wiseman M. S. , Kim Y. K. , Dugan F. M. , Rogers J. D. , Xiao C. L.
Published: July 2015

During surveys for postharvest diseases of apple and pear, an unknown postharvest fruit rot was observed in Washington State. The disease appeared to originate from infection of the stem and calyx tissue of the fruit or wounds on the fruit. An unknown pycnidial fungus was consistently isolated from the decayed fruit. Isolates from apple and pear were characterized and identified by molecular phylogenetic analysis and morphology. Pathogenicity of representative isolates on apple and pear fruit was tested under laboratory or field conditions. A BLAST search in GenBank showed that isolates differed from Phacidium lacerum and its synonym, Ceuthospora pinastri, by only 0 to 4 bp in sequences within part of the combined large ribosomal subunit + internal transcribed spacer + small ribosomal subunit regions. The phylogenetic analysis confirmed the taxonomic placement of the unknown fungus in the genus Phacidium, with the highest match being C. pinastri (formerly anamorphic P. lacerum) and with closely related taxa from GenBank forming congeneric clades. The fungus grew at 0 to 30°C and formed unilocular to multilocular pycnidial conidiomata on artificial media after approximately 5 to 7 days at room temperature. On potato dextrose agar incubated for a 12-h photoperiod, semi-immersed globose to subglobose pycnidial conidiomata were 250 to 1,000 μm in diameter (mean = 350), with 1 to 3 nonpapillate to slightly papillate ostioles and a buff conidial matrix. Conidia produced on phialides were 8 to 13 by 1.5 to 2.5 μm, hyaline, aseptate, cylindrical, with an abruptly tapered, typically slightly protuberant base, 2 to 3 guttules, and sometimes with a mucilaginous, flexuous, unbranched appendage which is attached to the apex of the conidium and disappears with age. Conidiogenous cells were flask shaped and 6 to 15 ×1.5 to 3 μm. Colony characteristics included felt-like aerial white mycelium, gray olivaceous at the center becoming greenish to colorless toward the margin, in concentric rings, with pycnidia forming in 5 to 7 days originating from the center of the plate. Morphological characteristics of the fungus had the greatest conformity with the description for C. pinastri. Based on molecular and morphological data, the fungus is identified as P. lacerum. ‘Fuji’ apple fruit and ‘d’Anjou’ pear fruit that were wounded, inoculated with representative isolates, and incubated at 0°C yielded the same symptoms as seen on decayed fruit collected from commercial fruit packinghouses. Stem-end rot, calyx-end rot, and wound-associated rot developed on fruit inoculated in the orchard after 3 months of cold storage. The fungus was reisolated from the diseased fruit. This is the first report of a fruit rot in apple and pear caused by P. lacerum. We propose Phacidium rot as the name of this disease.
Survival of Isolates of the US-22, US-23, and US-24 Clonal Lineages of Phytophthora infestans by Asexual Means in Tomato Seed at Cold Temperatures
Authors: Frost Kenneth E. , Seidl Johnson Anna C. , Gevens Amanda J.
Published: July 2015

Survival of Phytophthora infestans, causal agent of potato and tomato late blight, is thought to be negligible when exposed to freezing conditions typical of a Wisconsin winter. However, the persistence of relatively new P. infestans clonal lineages US-22, US-23, and US-24 within a production region during 2010 to 2014 warranted further investigation. We used tomato seed as a culture medium to determine the survival of P. infestans isolates representing the three lineages under temperatures of 18, 4, 0, −3, and −5°C for 11 time points (1 to 112 days postincubation). Survival varied interactively with temperature, duration of time at a temperature, and clonal lineage of the P. infestans isolate. US-22, -23, and -24 isolates survived for 112 days at 18 and 4°C, 84 days at 0°C, and 14 days at −3°C. US-23 survived longer at −3 and −5°C than did US-22 or US-24. The vigor of US-22 and US-24 isolates decreased with increasing exposure to cold temperatures, a trend that was not observed for the US-23 isolate. By calculating the length of time needed to kill the lineage isolates on infested tomato seed at five temperatures, we predicted that P. infestans would survive in 5% of tomato seed for 99, 25, and 16 days at 0, −3, and −5°C, respectively. We further applied a degree-day model to our empirical data to describe P. infestans survival as a function of cooling degree-day accumulations using archived soil temperatures at 5- and 10-cm depths at four Wisconsin locations over 27 years. The model indicated that survival of P. infestans in 5% of infested tomato seed would occur at 35 and 39% of the location–year combinations at 5- and 10-cm soil depths, respectively. Together, these data suggested that P. infestans has the potential to survive over the winter season by asexual means in infested tomato seed in Wisconsin and other Northern latitudes. Our cooling degree-day model for late blight in the tomato production system offers a tool for anticipating and mitigating disease based on integrated pest management concepts previously utilized for insects.
Agrobacterium tumefaciensGene Transfer: How a Plant Pathogen Hacks the Nuclei of Plant and Nonplant Organisms
Authors: Bourras Salim , Rouxel Thierry , Meyer Michel
Published: July 2015

Agrobacterium species are soilborne gram-negative bacteria exhibiting predominantly a saprophytic lifestyle. Only a few of these species are capable of parasitic growth on plants, causing either hairy root or crown gall diseases. The core of the infection strategy of pathogenic Agrobacteria is a genetic transformation of the host cell, via stable integration into the host genome of a DNA fragment called T-DNA. This genetic transformation results in oncogenic reprogramming of the host to the benefit of the pathogen. This unique ability of interkingdom DNA transfer was largely used as a tool for genetic engineering. Thus, the artificial host range of Agrobacterium is continuously expanding and includes plant and nonplant organisms. The increasing availability of genomic tools encouraged genome-wide surveys of T-DNA tagged libraries, and the pattern of T-DNA integration in eukaryotic genomes was studied. Therefore, data have been collected in numerous laboratories to attain a better understanding of T-DNA integration mechanisms and potential biases. This review focuses on the intranuclear mechanisms necessary for proper targeting and stable expression of Agrobacterium oncogenic T-DNA in the host cell. More specifically, the role of genome features and the putative involvement of host’s transcriptional machinery in relation to the T-DNA integration and effects on gene expression are discussed. Also, the mechanisms underlying T-DNA integration into specific genome compartments is reviewed, and a theoretical model for T-DNA intranuclear targeting is presented.
Within-host competition betweenBorrelia afzelii ospCstrains in wild hosts as revealed by massively parallel amplicon sequencing
Authors: Strandh Maria , Råberg Lars
Published: July 2015

Infections frequently consist of more than one strain of a given pathogen. Experiments have shown that co-infecting strains often compete, so that the infection intensity of each strain in mixed infections is lower than in single strain infections. Such within-host competition can have important epidemiological and evolutionary consequences. However, the extent of competition has rarely been investigated in wild, naturally infected hosts, where there is noise in the form of varying inoculation doses, asynchronous infections and host heterogeneity, which can potentially alleviate or eliminate competition. Here, we investigated the extent of competition betweenBorrelia afzeliistrains (as determined byospCgenotype) in three host species sampled in the wild. For this purpose, we developed a protocol for 454 amplicon sequencing ofospC, which allows both detection and quantification of each individual strain in an infection. Each host individual was infected with one to sixospCstrains. The infection intensity of each strain was lower in mixed infections than in single ones, showing that there was competition. Rank-abundance plots revealed that there was typically one dominant strain, but that the evenness of the relative infection intensity of the different strains in an infection increased with the multiplicity of infection. We conclude that within-host competition can play an important role under natural conditions despite many potential sources of noise, and that quantification by next-generation amplicon sequencing offers new possibilities to dissect within-host interactions in naturally infected hosts.
The evolution of bacterial resistance against bacteriophages in the horse chestnut phyllosphere is general across both space and time
Authors: Koskella Britt , Parr Nicole
Published: July 2015

Insight to the spatial and temporal scales of coevolution is key to predicting the outcome of host–parasite interactions and spread of disease. For bacteria infecting long-lived hosts, selection to overcome host defences is just one factor shaping the course of evolution; populations will also be competing with other microbial species and will themselves be facing infection by bacteriophage viruses. Here, we examine the temporal and spatial patterns of bacterial adaptation against natural phage populations from within leaves of horse chestnut trees. Using a time-shift experiment with both sympatric and allopatric phages from either contemporary or earlier points in the season, we demonstrate that bacterial resistance is higher against phages from the past, regardless of spatial sympatry or how much earlier in the season phages were collected. Similarly, we show that future bacterial hosts are more resistant to both sympatric and allopatric phages than contemporary bacterial hosts. Together, our results suggest the evolution of relatively general bacterial resistance against phages in nature and are contrasting to previously observed patterns of phage adaptation to bacteria from the same tree hosts over the same time frame, indicating a potential asymmetry in coevolutionary dynamics.
Building the microbiome in health and disease: niche construction and social conflict in bacteria
Authors: McNally Luke , Brown Sam P.
Published: July 2015

Microbes collectively shape their environment in remarkable ways via the products of their metabolism. The diverse environmental impacts of macro-organisms have been collated and reviewed under the banner of ‘niche construction’. Here, we identify and review a series of broad and overlapping classes of bacterial niche construction, ranging from biofilm production to detoxification or release of toxins, enzymes, metabolites and viruses, and review their role in shaping microbiome composition, human health and disease. Some bacterial niche-constructing traits can be seen as extended phenotypes, where individuals actively tailor their environment to their benefit (and potentially to the benefit of others, generating social dilemmas). Other modifications can be viewed as non-adaptive by-products from a producer perspective, yet they may lead to remarkable within-host environmental changes. We illustrate how social evolution and niche construction perspectives offer complementary insights into the dynamics and consequences of these traits across distinct timescales. This review highlights that by understanding the coupled bacterial and biochemical dynamics in human health and disease we can better manage host health.
Avian malaria: a new lease of life for an old experimental model to study the evolutionary ecology ofPlasmodium
Authors: Pigeault Romain , Vézilier Julien , Cornet Stéphane , Zélé Flore , Nicot Antoine , Perret Philippe , Gandon Sylvain , Rivero Ana
Published: July 2015

Avian malaria has historically played an important role as a model in the study of human malaria, being a stimulus for the development of medical parasitology. Avian malaria has recently come back to the research scene as a unique animal model to understand the ecology and evolution of the disease, both in the field and in the laboratory. Avian malaria is highly prevalent in birds and mosquitoes around the world and is amenable to laboratory experimentation at each stage of the parasite's life cycle. Here, we take stock of 5 years of experimental laboratory research carried out usingPlasmodium relictumSGS1, the most prevalent avian malaria lineage in Europe, and its natural vector, the mosquitoCulex pipiens. For this purpose, we compile and analyse data obtained in our laboratory in 14 different experiments. We provide statistical relationships between different infection-related parameters, including parasitaemia, gametocytaemia, host morbidity (anaemia) and transmission rates to mosquitoes. This analysis provides a wide-ranging picture of the within-host and between-host parameters that may bear on malaria transmission and epidemiology.
Crossing the scale from within-host infection dynamics to between-host transmission fitness: a discussion of current assumptions and knowledge
Authors: Handel Andreas , Rohani Pejman
Published: July 2015

The progression of an infection within a host determines the ability of a pathogen to transmit to new hosts and to maintain itself in the population. While the general connection between the infection dynamics within a host and the population-level transmission dynamics of pathogens is widely acknowledged, a comprehensive and quantitative understanding that would allow full integration of the two scales is still lacking. Here, we provide a brief discussion of both models and data that have attempted to provide quantitative mappings from within-host infection dynamics to transmission fitness. We present a conceptual framework and provide examples of studies that have taken first steps towards development of a quantitative framework that scales from within-host infections to population-level fitness of different pathogens. We hope to illustrate some general themes, summarize some of the recent advances and—maybe most importantly—discuss gaps in our ability to bridge these scales, and to stimulate future research on this important topic.
Computing the Internode Certainty and related measures from partial gene trees
Authors: Kobert Kassian , Salichos Leonidas , Rokas Antonis , Stamatakis Alexandros
Published: July 2015

We present, implement, and evaluate an approach to calculate the internode certainty and tree certainty on a given reference tree from a collection of partial gene trees. Previously, the calculation of these values was only possible from a collection of gene trees with exactly the same taxon set as the reference tree. An application to sets of partial gene trees requires mathematical corrections in the internode certainty and tree certainty calculations. We implement our methods in RAxML and test them on empirical data sets. These tests imply that the inclusion of partial trees does matter. However, in order to provide meaningful measurements, any data set should also include trees containing the full species set.
Divergence patterns of genic copy number variation in natural populations of the house mouse (Mus musculus domesticus) reveal three conserved genes with major population-specific expansions
Authors: Pezer Željka , Harr Bettina , Teschke Meike , Babiker Hiba , Tautz Diethard
Published: July 2015

Copy number variation represents a major source of genetic divergence, yet the evolutionary dynamics of genic copy number variation in natural populations during differentiation and adaptation remain unclear. We applied a read depth approach to genome resequencing data to detect copy number variants (CNVs) ≥1 kb in wild-caught mice belonging to four populations ofMus musculus domesticus. We complemented the bioinformatics analyses with experimental validation using droplet digital PCR. The specific focus of our analysis is CNVs that include complete genes, as these CNVs could be expected to contribute most directly to evolutionary divergence. In total, 1863 transcription units appear to be completely encompassed within CNVs in at least one individual when compared to the reference assembly. Further, 179 of these CNVs show population-specific copy number differences, and 325 are subject to complete deletion in multiple individuals. Among the most copy-number variable genes are three highly conserved genes that encode the splicing factor CWC22, the spindle protein SFI1, and the Holliday junction recognition protein HJURP. These genes exhibit population-specific expansion patterns that suggest involvement in local adaptations. We found that genes that overlap with large segmental duplications are generally more copy-number variable. These genes encode proteins that are relevant for environmental and behavioral interactions, such as vomeronasal and olfactory receptors, as well as major urinary proteins and several proteins of unknown function. The overall analysis shows that genic CNVs contribute more to population differentiation in mice than in humans and may promote and speed up population divergence.
Flowering Locus C’s Lessons: Conserved Chromatin Switches Underpinning Developmental Timing and Adaptation
Authors: Hepworth Jo , Dean Caroline
Published: July 2015

Analysis of how seasonal cues influence the timing of the floral transition has revealed many important principles for how epigenetic regulation can integrate a variety of environmental cues with developmental signals. The study of the pathways that necessitate overwintering in plants and their ability to respond to prolonged cold (the vernalization requirement and response pathways) has elaborated different chromatin regulatory pathways and the involvement of noncoding RNAs. The major target of these vernalization pathways in Arabidopsis (Arabidopsis thaliana) is Flowering Locus C (FLC). A relatively simple picture of FLC regulation is emerging of a few core complexes and mechanisms that antagonize each other’s actions. This balance provides a fine degree of control that has nevertheless permitted evolution of a wide range of natural variation in vernalization in Arabidopsis. Similar simple routes of adaptation may underlie life history variation between species.
Sequence Motifs in Transit Peptides Act as Independent Functional Units and Can Be Transferred to New Sequence Contexts
Authors: Lee Dong Wook , Woo Seungjin , Geem Kyoung Rok , Hwang Inhwan
Published: July 2015

A large number of nuclear-encoded proteins are imported into chloroplasts after they are translated in the cytosol. Import is mediated by transit peptides (TPs) at the N termini of these proteins. TPs contain many small motifs, each of which is critical for a specific step in the process of chloroplast protein import; however, it remains unknown how these motifs are organized to give rise to TPs with diverse sequences. In this study, we generated various hybrid TPs by swapping domains between Rubisco small subunit (RbcS) and chlorophyll a/b-binding protein, which have highly divergent sequences, and examined the abilities of the resultant TPs to deliver proteins into chloroplasts. Subsequently, we compared the functionality of sequence motifs in the hybrid TPs with those of wild-type TPs. The sequence motifs in the hybrid TPs exhibited three different modes of functionality, depending on their domain composition, as follows: active in both wild-type and hybrid TPs, active in wild-type TPs but inactive in hybrid TPs, and inactive in wild-type TPs but active in hybrid TPs. Moreover, synthetic TPs, in which only three critical motifs from RbcS or chlorophyll a/b-binding protein TPs were incorporated into an unrelated sequence, were able to deliver clients to chloroplasts with a comparable efficiency to RbcS TP. Based on these results, we propose that diverse sequence motifs in TPs are independent functional units that interact with specific translocon components at various steps during protein import and can be transferred to new sequence contexts.
Programming new geometry restraints: parallelity of atomic groups
Authors: Sobolev Oleg V. , Afonine Pavel V. , Adams Paul D. , Urzhumtsev Alexandre
Published: July 2015

Improvements in structural biology methods, in particular crystallography and cryo-electron microscopy, have created an increased demand for the refinement of atomic models against low-resolution experimental data. One way to compensate for the lack of high-resolution experimental data is to use a priori information about model geometry that can be utilized in refinement in the form of stereochemical restraints or constraints. Here, the definition and calculation of the restraints that can be imposed on planar atomic groups, in particular the angle between such groups, are described. Detailed derivations of the restraint targets and their gradients are provided so that they can be readily implemented in other contexts. Practical implementations of the restraints, and of associated data structures, in the Computational Crystallography Toolbox (cctbx) are presented.
Two novel ferrocenyl dipeptide-like compounds generatedviathe Ugi four-component reaction
Authors: Shao Guang-Kui , Zhao Mei , Wei Zheng , Ma Jian-Ping , Guo Dian-Shun
Published: July 2015

The Ugi four-component reaction, a powerful method for the synthesis of diverse dipeptide-like derivatives in combinatorial chemistry, was used to synthesize (S)-1′-{N-[1-(anthracen-9-yl)-2-(tert-butylamino)-2-oxoethyl]-N-(4-methoxyphenyl)carbamoyl}ferrocene-1-carboxylic acid dichloromethane disolvate, [Fe(C6H5O2)(C33H31N2O3)]·2CH2Cl2, (I), and (S)-2-(anthracen-9-yl)-N-tert-butyl-2-[N-(4-methylphenyl)ferrocenylformamido]acetamide, [Fe(C5H5)(C33H31N2O2)], (II). They adopt broadly similar molecular conformations, with near-eclipsed cyclopentadienyl rings and near-perpendicular amide planes in their dipeptide-like chains, one of which is almost coplanar with its attached cyclopentadienyl ring but perpendicular to the aromatic ring bound to the N atom. In the supramolecular structure of (I), a two-dimensional network is constructed based on molecular dimers and a combination of intermolecular O—H...O, N—H...O and C—H...O hydrogen bonds, formingR22(11),R22(16),R22(22) andC(9) motifs. These two-dimensional networks are connected by C—H...O and C—H...Cl contacts to create a three-dimensional framework, where one dichloromethane solvent molecule acts as a bridge between two neighbouring networks. In the packing of (II), classical hydrogen bonds are absent and an infinite one-dimensional chain is generatedviaa combination of C—H...O hydrogen bonds and C—H...π interactions, producing aC(7) motif. This work describes a simple synthesis and the supramolecuar structures of ferrocenyl dipeptide-like compounds and is significant in the development of redox-active receptors.
Synthesis and crystal structures of two coordination polymers and a binuclear cadmium(II) complex containing 3- and 4-aminobenzoate ligands
Authors: Zhou Dong-Mei , Zhao Xiao-Lan , Liu Feng-Yi , Kou Jun-Feng
Published: July 2015

Due to their wide range of coordination modes and versatile conformations when binding to metal atoms, multicarboxylate ligands are of interest in the design of metal–organic frameworks (MOFs). Three CdIIcomplexes, namelycatena-poly[diammonium [[chloridocadmium(II)]-di-μ-chlorido-[chloridocadmium(II)]-bis(μ-3-aminobenzoato)-κ3N:O,O′;κ3O,O′:N]], {(NH4)[CdCl2(C7H6NO2)]}n, (I),catena-poly[[[aquacadmium(II)]-bis(μ-4-aminobenzoato)-κ3N:O,O′;κ3O,O′:N] monohydrate], {[Cd(C7H6NO2)2(H2O)]·H2O}n, (II), and di-μ-acetato-κ4O:O′-bis[(4-aminobenzoato-κ2O,O′)(2,2′-bipyridine-κ2N,N′)cadmium(II)], [Cd2(CH3COO)2(C7H6NO2)2(C10H8N2)2], (III), with different stuctural forms are reported. Complex (I) has a one-dimensional ladder structure, with strong N—H...O and weak N—H...Cl hydrogen bonds linking the cations and anions in the three-dimensional supramolecular structure. Complex (II) has a one-dimensional chain structure. Extensive O—H...O and N—H...O hydrogen bonds between the anionic ligands and the solvent water molecules and π–π stacking interactions between the centroids of the benzene rings lead to the three-dimensional supramolecular structure. Complex (III) is a binuclear molecule which is extended into a three-dimensional supramolecular structureviastrong N—H...O and weak C—H...O hydrogen bonds.
Structure of a dinuclear cadmium complex with 2,2′-bipyridine, monodentate nitrate and 3-carboxy-6-methylpyridine-2-carboxylate ligands: intramolecular carbonyl(lone pair)...π(ring) and nitrate(π)...π(ring) interactions
Authors: Granifo Juan , Suarez Sebastián , Baggio Ricardo
Published: July 2015

The centrosymmetric dinuclear complex bis(μ-3-carboxy-6-methylpyridine-2-carboxylato)-κ3N,O2:O2;κ3O2:N,O2-bis[(2,2′-bipyridine-κ2N,N′)(nitrato-κO)cadmium] methanol monosolvate, [Cd2(C8H6NO4)2(NO3)2(C10H8N2)2]·CH3OH, was isolated as colourless crystals from the reaction of Cd(NO3)2·4H2O, 6-methylpyridine-2,3-dicarboxylic acid (mepydcH2) and 2,2′-bipyridine in methanol. The asymmetric unit consists of a CdIIcation bound to a μ-κ3N,O2:O2-mepydcH−anion, anN,N′-bidentate 2,2′-bipyridine group and anO-monodentate nitrate anion, and is completed with a methanol solvent molecule at half-occupancy. The Cd complex unit is linked to its centrosymmetric image through a bridging mepydcH−carboxylate O atom to complete the dinuclear complex molecule. Despite a significant variation in the coordination angles, indicating a considerable departure from octahedral coordination geometry about the CdIIatom, the Cd—O and Cd—N distances in this complex are surprisingly similar. The crystal structure consists of O—H...O hydrogen-bonded chains parallel toa, further bound by C—H...O contacts alongbto form planar two-dimensional arrays parallel to (001). The juxtaposed planes form interstitial columnar voids that are filled by the methanol solvent molecules. These in turn interact with the complex molecules to further stabilize the structure. A search in the literature showed that complexes with the mepydcH−ligand are rare and complexes reported previously with this ligand do not adopt the μ-κ3coordination mode found in the title compound.
Crystal structure of sepaconitine, a C19-diterpenoid alkaloid from the roots ofAconitum sinomontanumNakai
Authors: Shi Xin-Wei , Lu Qiang-Qiang , Zhou Jun-Hui , Cui Xin-Ai
Published: July 2015

The title compound [systematic name: [(1α,14α,16β)-20-ethyl-8,9,10-trihydroxy-1,14,16-trimethoxyaconitan-4-yl 2-aminobenzoate], C30H42N2O8, a natural C19-diterpenoid alkaloid, possesses an aconitane carbon skeleton with four six-membered rings and two five-membered rings. The fused ring system contains two chair, one boat, one twist-boat and two envelope conformations. Intramolecular N—H...O hydrogen bonds are observed between the amino and carbonyl groups. The molecules are linked togetherviaO—H...O hydrogen bonds, forming a three-dimensional framework.
Crystal structure of (R)-6-fluoro-2-[(S)-oxiran-2-yl]chroman
Authors: Rousselin Yoann , Laureano Hugo , Clavel Alexandre
Published: July 2015

The title compound, C11H11FO2, is a building block in the synthesis of the active pharmaceutical ingredient DL-nebivolol. The synthesis starting from the enantiomerically pure (R)-6-fluoro-4-oxo-3,4-dihydro-2H-chromene-2-carboxylic acid resulted in a mixture of two stereoisomers, namely (R)-6-fluoro-2-[(S)-oxiran-2-yl]chroman and (R)-6-fluoro-2-[(R)-oxiran-2-yl]chroman. The mixture was separated by column chromatography but only one stereoisomer crystallized. The X-ray structure analysis revealed that the solid consisted of theR,Sisomer. A similar procedure was repeated for (S)-6-fluoro-4-oxo-3,4-dihydro-2H-chromene-2-carboxylic acid and, in this case, theS,Risomer was produced as a crystalline solid. Thus, all four stereoisomers of the title epoxide were obtained and their absolute configuration was assigned. The crystal studied was refined as an inversion twin.
Crystal structure of (Z)-3-[5-chloro-2-(prop-2-ynyloxy)phenyl]-3-hydroxy-1-[4-(trifluoromethyl)phenyl]prop-2-en-1-one
Authors: Dalal Aarti , Kamboj Ramesh C. , Kumar Dinesh , Sharma Mahendra Kumar , Selvarajan Nagendran
Published: July 2015

The title compound, C19H12ClF3O3, obtained by the photochemical transformation of 2-[5-chloro-2-(prop-2-ynyloxy)benzoyl]-3-[4-(trifluoromethyl)phenyl]oxirane adopts aZconformation with respect to the enolic C=C double bond. The dihedral angle between the benzene rings is 12.25 (16)° and an intramolecular O—H...O hydrogen bond closes anS(6) ring. An intramolecular C—H...O interaction also leads to anS(6) ring. In the crystal, very weak C—H...O interactions and short Cl...Cl contacts [3.3221 (16) Å] are seen, as well as weak aromatic π–π stacking interactions [centroid–centroid separation = 3.879 (2) Å].
Crystal structure of 2,5-dimethyl-3-(2-methylphenylsulfinyl)-1-benzofuran
Authors: Choi Hong Dae , Lee Uk
Published: July 2015

In the title compound, C17H16O2S, the dihedral angle between the benzofuran ring system [r.m.s. deviation = 0.009 (1) Å] and the 2-methylphenyl ring is 86.72 (4)°. In the crystal, weak C—H...O hydrogen bonds link the molecules into columns along theb-axis direction.
Crystal structure of 2-(2-methylphenyl)-1,3-thiazolo[4,5-b]pyridine
Authors: El-Hiti Gamal A. , Smith Keith , Hegazy Amany S. , Alanazi Saud A. , Kariuki Benson M.
Published: July 2015

In the title molecule, C13H10N2S, the dihedral angle between the planes through the non-H atoms of the methylbenzene and thiazolopyridine groups is 36.61 (5)°. In the crystal, the thiazolopyridine groups of inversion-related molecules overlap, with a minimum ring-centroid separation of 3.6721 (9) Å. Furthermore, the methylbenzene groups from neighbouring molecules interact edge-to-face at an angle of 71.66 (5)°. In addition, weak C—H... N hydrogen bonds form chains exending along [100].
Crystal structure of the enol form of mesotrione: a benzoylcyclohexanedione herbicide
Authors: Kang Gihaeng , Kim Jineun , Park Hyunjin , Kim Tae Ho
Published: July 2015

The title compound [systematic name: 3-hydroxy-2-(4-methylsulfonyl-2-nitrobenzoyl)cyclohex-2-enone], C14H13NO7S, is the enol form of a benzoylcyclohexanedione herbicide. As a result of this tautomerization, there is intramolecular O—H...O hydrogen bond enclosing anS(6) ring motif. The cyclohexene ring has an envelope conformation, with the central CH2C atom as the flap. Its mean plane is inclined to the benzene ring by 87.46 (8)°. In the crystal, molecules are linked by a series of C—H...O hydrogen bonds, forming a three-dimensional framework.
Crystal structure of 2-amino-7-hydroxy-4-(4-hydroxyphenyl)-4H-chromene-3-carbonitrile
Authors: Horton Peter N. , Akkurt Mehmet , Mohamed Shaaban K. , Younes Sabry H. H. , Albayati Mustafa R.
Published: July 2015

In the title compound, C16H12N2O3, the chromene ring system is nearly planar [maximum deviation from the mean plane = 0.057 (1) Å], and is almost perpendicular to the benzene ring, with a dihedral angle of 85.29 (5)°. In the crystal, molecules are linked by classical N—H...O, O—H...O and O—H...N hydrogen bonds, and weak C—H...O hydrogen bonds, forming a three-dimensional supramolecular network. Furthermore, a weak π–π stacking interaction is observed; the centroid-to-centroid distance is 3.7260 (7) Å.
A real-time test of food hazard awareness
Authors: Millman Caroline , Rigby Dan , Jones Davey , Edwards-Jones Gareth
Published: July 2015

Purpose

– Food poisoning attributable to the home generates a large disease burden, yet is an unregulated and largely unobserved domain. Investigating food safety awareness and routine practices is fraught with difficulties. The purpose of this paper is to develop and apply a new survey tool to elicit awareness of food hazards. Data generated by the approach are analysed to investigate the impact of oberservable heterogeneity on food safety awareness.

Design/methodology/approach

– The authors develop a novel Watch-and-Click survey tool to assess the level of awareness of a set of hazardous food safety behaviours in the domestic kitchen. Participants respond to video footage stimulus, in which food hazards occur, via mouse clicks/screen taps. This real-time response data is analysed via estimation of count and logit models to investigate how hazard identification patterns vary over observable characteristics.

Findings

– User feedback regarding the Watch-and-Click tool approach is extremely positive. Substantive results include significantly higher hazard awareness among the under 60s. People who thought they knew more than the average person did indeed score higher but people with food safety training/experience did not. Vegetarians were less likely to identify four of the five cross-contamination hazards they observed.

Originality/value

– A new and engaging survey tool to elicit hazard awareness with real-time scores and feedback is developed, with high levels of user engagement and stakeholder interest. The approach may be applied to elicit hazard awareness in a wide range of contexts including education, training and research.