bluuebunny/crossref_metadata_2025 huggingface dataset:
The house spider genome reveals an ancient whole-genome duplication during arachnid evolution
Authors: Schwager Evelyn E. , Sharma Prashant P. , Clarke Thomas , Leite Daniel J. , Wierschin Torsten , Pechmann Matthias , Akiyama-Oda Yasuko , Esposito Lauren , Bechsgaard Jesper , Bilde Trine , Buffry Alexandra D. , Chao Hsu , Dinh Huyen , Doddapaneni HarshaVardhan , Dugan Shannon , Eibner Cornelius , Extavour Cassandra G. , Funch Peter , Garb Jessica , Gonzalez Luis B. , Gonzalez Vanessa L. , Griffiths-Jones Sam , Han Yi , Hayashi Cheryl , Hilbrant Maarten , Hughes Daniel S.T. , Janssen Ralf , Lee Sandra L. , Maeso Ignacio , Murali Shwetha C. , Muzny Donna M. , da Fonseca Rodrigo Nunes , Paese Christian L. B. , Qu Jiaxin , Ronshaugen Matthew , Schomburg Christoph , Schönauer Anna , Stollewerk Angelika , Torres-Oliva Montserrat , Turetzek Natascha , Vanthournout Bram , Werren John H. , Wolff Carsten , Worley Kim C. , Bucher Gregor , Gibbs Richard A. , Coddington Jonathan , Oda Hiroki , Stanke Mario , Ayoub Nadia A. , Prpic Nikola-Michael , Flot Jean-Frangois , Posnien Nico , Richards Stephen , McGregor Alistair P.
Published: February 2017

The duplication of genes can occur through various mechanisms and is thought to make a major contribution to the evolutionary diversification of organisms. There is increasing evidence for a large-scale duplication of genes in some chelicerate lineages including two rounds of whole genome duplication (WGD) in horseshoe crabs. To investigate this further we sequenced and analyzed the genome of the common house spiderParasteatoda tepidariorum.We found pervasive duplication of both coding and non-coding genes in this spider, including two clusters of Hox genes. Analysis of synteny conservation across theP. tepidariorumgenome suggests that there has been an ancient WGD in spiders. Comparison with the genomes of other chelicerates, including that of the newly sequenced bark scorpionCentruroides sculpturatus, suggests that this event occurred in the common ancestor of spiders and scorpions and is probably independent of the WGDs in horseshoe crabs. Furthermore, characterization of the sequence and expression of the Hox paralogs inP. tepidariorumsuggests that many have been subject to neofunctionalization and/or subfunctionalization since their duplication, and therefore may have contributed to the diversification of spiders and other pulmonate arachnids.
The impact of genome-wide association studies on biomedical research publications
Authors: Struck Travis J. , Mannakee Brian K. , Gutenkunst Ryan N.
Published: February 2017

The past decade has seen major investment in genome-wide association studies (GWAS), with the goal of identifying and motivating research on novel genes involved in complex human disease. To assess whether this goal is being met, we quantified the effect of GWAS on the overall distribution of biomedical research publications and on the subsequent publication history of genes newly associated with complex disease. We found that the historical skew of publications toward genes involved in Mendelian disease has not changed since the advent of GWAS. Genes newly implicated by GWAS in complex disease do experience additional publications compared to control genes, and they are more likely to become exceptionally studied. But the magnitude of both effects has declined dramatically over the past decade. Our results suggest that reforms to encourage follow-up studies may be needed for GWAS to most successfully guide biomedical research toward the molecular mechanisms underlying complex human disease.

Author summary

Over the past decade, thousands of genome-wide association studies (GWAS) have been performed to link genetic variation with complex human disease. A major goal of such studies is to identify novel disease genes, so they can be further studied. We tested whether this goal is being met, by studying patterns of scientific research publications on human genes. We found that publications are still concentrated on genes involved in simple Mendelian disease, even after the advent of GWAS. Compared to other genes, disease genes discovered by GWAS do experience additional publications, but that effect has declined dramatically since GWAS were first performed. Our results suggest that the ability of GWAS to stimulate research into novel disease genes is declining. To realize the full potential of GWAS to reveal the molecular mechanisms driving human disease, this decline and the reasons for it must be understood, so that it can be reversed.
The depletion of MARVELD1 leads to placenta accreta via integrin β4-dependent trophoblast cell invasion
Authors: Chen Yue , Zhang Hui , Han Fang , Yue Lei , Qiao Chunxiao , Zhang Yao , Dou Peng , Liu Weizhe , Li Yu
Published: February 2017

Astract

The mammalian placenta is a remarkable organ. It serves as the interface between the mother and the fetus. Proper invasion of trophoblast cells into the maternal decidua is required for a successful pregnancy. Previous studies have found that the adhesion molecule integrin β4 plays important roles during trophoblast cell invasion. Here, we found that the overall birth rate of the MARVELD1 knockout mouse is much lower than that of the wild-type mouse (P<0.001). In E18.5 MARVELD1 knockout mice, we observed an over-invasion of trophoblast cells, and indeed, the pregnant mice had a partial placenta accreta phenotype. The HTR8/SVneo cell line was used as an in vitro model to elucidate the underlying mechanisms of MARVELD1-mediated trophoblast invasion. We detected a diminished expression of integrin β4 upon the downregulation of MARVELD1 and enhanced migration and invasive abilities of trophoblast cells both in vivo and in vitro. The integrin β4 rescue assay also supported the results. In conclusion, this study found that MARVELD1 mediated the invasion of trophoblast cells via regulating the expression of integrin β4.
Accumulation of Minor Alleles of Common SNPs in Schizophrenia
Authors: He Pei , Lei Xiaoyun , Yuan Dejian , Zhu Zuobin , Huang Shi
Published: February 2017

Schizophrenia is a common neuropsychiatric disorder with a lifetime risk of 1%. A number of large scale genome wide association studies have identified numerous individual risk single nucleotide polymorphisms (SNPs) whose precise roles in schizophrenia remain unknown. Accumulation of many of these risk alleles has been found to be a more important risk factor. Consistently, recent studies showed a role for enrichment of minor alleles (MAs) in complex diseases. Here we studied the role of MAs in general in schizophrenia using public datasets. Relative to matched controls, schizophrenia cases showed higher minor allele content (MAC), especially for the sporadic cases. By linkage analysis, we identified 82 419 SNPs that could be used to predict 2.2% schizophrenia cases with 100% certainty. Pathway enrichment analysis of these SNPs identified 17 pathways, 15 of which are known to be linked with Schizophrenia with the remaining 2 associated with other mental disorders. These results suggest a role for a collective effect of MAs in schizophrenia and provide a method to genetically screen for schizophrenia.
Metabolic Network Analysis and Metatranscriptomics Reveals Auxotrophies and Nutrient Sources of the Cosmopolitan Freshwater Microbial Lineage aci
Authors: Hamilton Joshua J. , Garcia Sarahi L. , Brown Brittany S. , Oyserman Ben O. , Moya-Flores Francisco , Bertilsson Stefan , Malmstrom Rex R. , Forest Katrina T. , McMahon Katherine D.
Published: February 2017

An explosion in the number of available genome sequences obtained through metagenomics and single-cell genomics has enabled a new view of the diversity of microbial life, yet we know surprisingly little about how microbes interact with each other or their environment. In fact, the majority of microbial species remain uncultivated, while our perception of their ecological niches is based on reconstruction of their metabolic potential. In this work, we demonstrate how the “seed set framework”, which computes the set of compounds that an organism must acquire from its environment (1), enables computational analysis of metabolic reconstructions, while providing new insights into a microbe’s metabolic capabilities, such as nutrient use and auxotrophies. We apply this framework to members of the ubiquitous freshwater Actinobacterial lineage acI, confirming and extending previous experimental and genomic observations implying that acI bacteria are heterotrophs reliant on peptides and saccharides. We also present the first metatranscriptomic study of the acI lineage, revealing high expression of transport proteins and the light-harvesting protein actinorhodopsin. Putative transport proteins complement predictions of nutrients and essential metabolites while providing additional support to the hypothesis that members of the acI are photoheterotrophs.

Importance

The metabolic activity of uncultivated microorganisms contributes to numerous ecosystem processes, ranging from nutrient cycling in the environment to influencing human health and disease. Advances in sequencing technology have enabled the assembly of genomes for these microorganisms, but our ability to generate reference genomes far outstrips our ability to analyze them. Common approaches to analyzing microbial metabolism require reconstructing the entirety of an organism’s metabolic pathways, or performing targeted searches for genes involved in a specific process. This paper presents a third approach, in which draft metabolic reconstructions are used to identify compounds through which an organism may interact with its environment. These compounds can then guide more intensive metabolic reconstruction efforts, and also provide new hypotheses about the specific contributions microbes make to ecosystem-scale metabolic processes.
CpG methylation accounts for genome-wide C>T mutation variation and cancer driver formation across cancer types
Authors: Poulos Rebecca C. , Olivier Jake , Wong Jason W. H.
Published: February 2017

Cytosine methylation (5mC) is vital for cellular function, and yet 5mC sites are also commonly mutated in the genome. In this study, we analyse the genomes of over 900 cancer samples, together with tissue type-specific methylation and replication timing data. We describe a strong mutation-methylation association in colorectal cancers with microsatellite instability (MSI) or withPolymerase epsilon (POLE)exonuclease domain mutation. We describe a potential role for mismatch repair in the correction of mismatches resulting from deamination of 5mC, and propose a mutator phenotype to exist inPOLE-mutant cancers specifically at 5mC sites. We also associatePOLE-mutant hotspot coding mutations inAPCandTP53with CpG methylation. Analysing mutations across additional cancer types, we identify nucleotide excision repair- and AID/APOBEC-induced processes to underlie differential mutation-methylation associations in certain cancer subtypes. This study reveals differential associations vital for accurately mapping regional variation in mutation density and pinpointing driver mutations in cancer.
Antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase: pseudouridimycin
Authors: Maffioli Sonia I. , Zhang Yu , Degen David , Carzaniga Thomas , Del Gatto Giancarlo , Serina Stefania , Monciardini Paolo , Mazzetti Carlo , Guglierame Paola , Candiani Gianpaolo , Chiriac Alina Iulia , Facchetti Giuseppe , Kaltofen Petra , Sahl Hans-Georg , Dehò Gianni , Donadio Stefano , Ebright Richard H.
Published: February 2017

There is an urgent need for new antibacterial drugs effective against bacterial pathogens resistant to current drugs1–2. Nucleoside-analog inhibitors (NAIs) of viral nucleotide polymerases have had transformative impact in treatment of HIV3and HCV4. NAIs of bacterial RNA polymerase (RNAP) potentially could have major impact on treatment of bacterial infection, particularly because functional constraints on substitution of RNAP nucleoside triphosphate (NTP) binding sites4-5could limit resistance emergence4-5. Here we report the discovery, from microbial extract screening, of an NAI that inhibits bacterial RNAP and exhibits antibacterial activity against a broad spectrum of drug-sensitive and drug-resistant bacterial pathogens: pseudouridimycin (PUM). PUM is a novel microbial natural product consisting of a formamidinylated, N-hydroxylated Gly-Gln dipeptide conjugated to 6'-amino-pseudouridine. PUM potently and selectively inhibits bacterial RNAP in vitro, potently and selectively inhibits bacterial growth in culture, and potently clears infection in a mouse model ofStreptococcus pyogenesperitonitis. PUM inhibits RNAP through a binding site on RNAP (the "i+1" NTP binding site) and mechanism (competition with UTP for occupancy of the "i+1" NTP binding site) that differ from those of the RNAP inhibitor and current antibacterial drug rifampin (Rif). PUM exhibits additive antibacterial activity when co-administered with Rif, exhibits no cross-resistance with Rif, and exhibits a spontaneous resistance rate an order-of-magnitude lower than that of Rif. The results provide the first example of a selective NAI of bacterial RNAP, provide an advanced lead compound for antibacterial drug development, and provide structural information and synthetic routes that enable lead optimization for antibacterial drug development.
Re-evaluating inheritance in genome evolution: widespread transfer of LINEs between species
Authors: Ivancevic Atma M. , Daniel Kortschak R. , Bertozzi Terry , Adelson David L.
Published: February 2017

Transposable elements (TEs) are mobile DNA sequences, colloquially known as ‘jumping genes’ because of their ability to replicate to new genomic locations. Given a vector of transfer (e.g. tick or virus), TEs can jump further: between organisms or species in a process known as horizontal transfer (HT). Here we propose that LINE-1 (L1) and Bovine-B (BovB), the two most abundant TE families in mammals, were initially introduced as foreign DNA via ancient HT events. Using a 503-genome dataset, we identify multiple ancient L1 HT events in eukaryotes and provide evidence that L1s infiltrated the mammalian lineage after the monotreme-therian split. We also extend the BovB paradigm by increasing the number of estimated transfer events compared to previous studies, finding new potential blood-sucking parasite vectors and occurrences in new lineages (e.g. bats, frog). Given that these TEs make up nearly half of the genome sequence in today’s mammals, our results provide the first evidence that HT can have drastic and long-term effects on the new host genomes. This revolutionizes our perception of genome evolution to consider external factors, such as the natural introduction of foreign DNA. With the advancement of genome sequencing technologies and bioinformatics tools, we anticipate our study to be the first of many large-scale phylogenomic analyses exploring the role of HT in genome evolution.

Significance statement

LINE-1 (L1) elements occupy about half of most mammalian genomes (1), and they are believed to be strictly vertically inherited (2). Mutagenic L1 insertions are thought to account for approximately 1 of every 1000 random, disease-causing insertions in humans (4-7). Our research indicates that the very presence of L1s in humans, and other therian mammals, is due to an ancient transfer event – which has drastic implications for our perception of genome evolution. Usinga machinaanalyses over 503 genomes, we trace the origins of L1 and BovB retrotransposons across the tree of life, and provide evidence of their long-term impact on eukaryotic evolution.
A nanobody-based toolset to investigate the role of protein localization and dispersal inDrosophila
Authors: Harmansa Stefan , Alborelli Ilaria , Caussinus Emmanuel , Affolter Markus
Published: February 2017

Investigating the role of protein localization is crucial to understand protein function in cells or tissues. However, in many cases the role of different subcellular fractions of given proteins along the apical-basal axis of polarized cells has not been investigatedin vivo, partially due to lack of suitable tools. Here, we present the GrabFP system, a nanobody-based toolbox to modify the localization and the dispersal of GFP-tagged proteins along the apical-basal axis of polarized cells. We show that the GrabFP system is an effective and easy-to-implement tool to mislocalize cytosolic and transmembrane GFP-tagged proteins and thereby functionally investigate protein localization along the apical-basal axis. We use the GrabFP system as a tool to study the extracellular dispersal of the Decapentaplegic (Dpp) protein and show that the Dpp gradient forming in the lateral plane of theDrosophilawing disc epithelium is essential for patterning of the wing imaginal disc.
Gene ORGANizer: Linking Genes to the Organs They Affect
Authors: Gokhman David , Kelman Guy , Amartely Adir , Gershon Guy , Tsur Shira , Carmel Liran
Published: February 2017

One of the biggest challenges in studying how genes work is understanding their effect on the physiology and anatomy of the body. Existing tools try to address this using indirect features, such as expression levels and biochemical pathways. Here, we present Gene ORGANizer (geneorganizer.huji.ac.il), a phenotype-based tool that directly links human genes to the body parts they affect. It is built upon an exhaustive curated database that links more than 7,000 genes to ∼150 anatomical parts using >150,000 gene-organ associations. The tool offers user-friendly platforms to analyze the anatomical effects of individual genes, and identify trends within groups of genes. We demonstrate how Gene ORGANizer can be used to make new discoveries, showing that chromosome X is enriched with genes affecting facial features, that positive selection targets genes with more constrained phenotypic effects, and more. We expect Gene ORGANizer to be useful in a variety of evolutionary, medical and molecular studies aimed at understanding the phenotypic effects of genes.
FAM83G/PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP
Authors: Cummins Timothy D. , Wu Kevin Z. L. , Bozatzi Polyxeni , Dingwell Kevin S. , Macartney Thomas , Wood Nicola T , Varghese Joby , Gourlay Robert , Campbell David G , Prescott Alan , Griffis Eric , Smith James C , Sapkota Gopal P
Published: February 2017

Our previous studies of PAWS1 (ProteinAssociatedWithSMAD1) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1 knockout cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization. Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration. PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae, suggesting that its association with CD2AP controls actin organization and cellular migration.

Summary statement

PAWS1/FAM83G controls cell migration by influencing the organisation of F-actin and focal adhesions and the distribution of the actin stress fibre network through its association with CD2AP.
Taenia soliumTAF6 and TAF9 binds to a putative Downstream Promoter Element present inTsTBP1gene core promoter
Authors: Rodríguez-Lima Oscar , García-Gutierrez Ponciano , Jimenez Lucía , Zarain-Herzberg Angel , Lazarini Roberto , Landa Abraham
Published: February 2017

We have cloned and characterized the gene encoding toTaenia soliumTATA binding protein 1 (TsTBP1). It spans 1481 bp and its coding region is interrupted by four introns that possess the consensus donor/acceptor sequences. It produces a protein of 238 amino acids residues, which presented all the classical motives of the TBP1. On the core promoter region we identified putative binding sites for NF1, AP-1, YY1, TAF1/TAF2 and TAF6/TAF9, and the TSS that corresponds to an A+1. Southern and Northern blot analysis showed that TsTBP1 is encoded by a single gene, which produce a messenger of about 1.1 kbp with a higher differential expression in adult than the larval stage. Moreover, two putative TATA boxes were identified at -97 and -69 bp (relative to the TSS), likewise a Downstream Promoter Element (DPE) was located at +27 to +31 bp. EMSA experiments did not show any component of cysticerci nuclear extracts bound to the putative TATA-box elements; in contrast TAF6 and TAF9 bind to the DPE, showing thatTsTBP1is a TATA-less gen. On the other hand, TAF6 and TAF9 were localized on the nucleus from cells ofT. crassicepscysticerci bladder walls. By using the amino acid sequences ofT. soliumTAF6 (TsTAF6) and TAF9 (TsTAF9), we constructed a molecular model showing interaction between DPE-TsTAF6 and TsTAF6-TsTAF9. Finally, anin silicoanalysis of the core promoters ofTaeniidaefamily genes showed that TATA-box and DPE are homologous to the mammalian elements, but not so the Inr. The low identity between TAF9 from cestodes and mammals open the possibility to use it as target to interrupt or modulate the transcription of TATA-box less genes in cestodes as a novel therapeutic strategy.

Author summary

Neurocysticercosis still being a health problem in developing countries. Mexico reports a prevalence of 2.5% in the total patients from National Institute of Neurology and Neurosurgery. Several efforts have been made in different fields to studyTaenia solium, and although the Genome Project has been published and released the genomic sequence of this parasite; the transcriptional mechanisms this organism remains unexplored. We isolated and characterizedTaenia soliumTATA-Binding Protein 1 (TsTBP1) gene and TBP-associated factor 6 and 9 cDNAs (TsTAF6andTsTAF9, respectively). Our principal findings are: 1.- Identification of cis and trans elements in the core promoter ofTsTBP1gene. 2.- TheTsTBP1gene is a TATA-less promoter. 3.- Cloning of cDNAs toTsTAF6andTsTAF9, 4.- Identification of a DPE in the core promoter ofTsTBP1gene, which interacts with TAF6 and TAF9, 5.- Construction of a molecular model that shows the interaction between DPE, TAF6, and TAF9; and 6.- A proposal of consensus sequences for TATA-box, Inr and DPE presented onTaeniidaefamily core promoters.
Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
Authors: Lees John A. , Croucher Nicholas J. , David Goldblatt , Francois Nosten , Julian Parkhill , Claudia Turner , Paul Turner , Stephen D. Bentley
Published: February 2017

Streptococcus pneumoniaeis a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, and the duration of carriage is an important consideration in modelling transmission dynamics and vaccine response. Existing studies of carriage duration variability are based at the serotype level only, and do not probe variation within lineages or fully quantify interactions with other environmental factors.

Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data. By combining these results with whole genome sequence data we estimate that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas host traits accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). For the locus effects, a genome-wide association study identified 16 loci which may have an effect on carriage duration independent of serotype. Hits at a genome-wide level of significance were to prophage sequences, suggesting infection by such viruses substantially affects carriage duration.

These results show that both serotype and non-serotype specific effects alter carriage duration in infants and young children and are more important than other environmental factors such as host genetics. This has implications for models of pneumococcal competition and antibiotic resistance, and leads the way for the analysis of heritability of complex bacterial traits.

Significance statement

Other than serotype, the genetic determinants of pneumococcal carriage duration are unknown. In this study we used longitudinal sampling to measure the duration of carriage in infants, and searched for any associated variation in the pan-genome. While we found that the pathogen genome explains most of the variability in duration, serotype did not fully account for this. Recent theoretical work has proposed the existence of alleles which alter carriage duration to explain the puzzle of continued coexistence of antibiotic-resistant and sensitive strains. Here we have shown that these alleles do exist in a natural population, and also identified candidates for the loci which fulfil this role. Together these findings have implications for future modelling of pneumococcal epidemiology and resistance.
rxncon 2.0: a language for executable molecular systems biology
Authors: Romers Jesper C. , Krantz Marcus
Published: February 2017

Large-scale knowledge bases and models become increasingly important to systematise and interpret empirical knowledge on cellular systems. In signalling networks, as opposed to metabolic networks, distinct modifications of and bonds between components combine into very large numbers of possible configurations, or microstates. These are essentially never measured in vivo, making explicit modelling strategies both impractical and problematic. Here, we presentrxncon2.0, the second generation rxncon language, as a tool to define signal transduction networks at the level of empirical data. By expressing both reactions and contingencies (contextual constraints on reactions) in terms of elemental states, both the combinatorial complexity and the discrepancy to empirical data can be minimised. It works as a higher-level language natural to biologists, which can be compiled into a range of graphical formats or executable models. Taken together, the rxncon language combines mechanistic precision with scalability in a composable and compilable language, that is designed for building executable knowledge bases on the molecular biology of signalling systems.
Genomic analysis ofPelements in natural populations ofDrosophila melanogaster
Authors: Bergman Casey M. , Nelson Michael G. , Bondarenko Vladyslav , Kozeretska Iryna A.
Published: February 2017

TheDrosophila melanogaster Ptransposable element provides one of the best cases of horizontal transfer of a mobile DNA sequence in eukaryotes. Invasion of natural populations by thePelement has led to a syndrome of phenotypes known as P-M hybrid dysgenesis that emerges when strains differing in theirPelement composition mate and produce offspring. Despite extensive research on many aspects ofPelement biology, many questions remain about the genomic basis of variation in P-M dysgenesis phenotypes in natural populations. Here we compare gonadal dysgenesis phenotypes and genomicPelement predictions for isofemale strains obtained from three worldwide populations ofD. melanogasterto illuminate the molecular basis of natural variation in cytotype status. We show that the number of predictedPelement insertions in genome sequences from isofemale strains is highly correlated across different bioinformatics methods, but the absolute number of insertions per strain is sensitive to method and filtering strategies. Regardless of method used, we find that the number of euchromaticPelement insertions predicted per strain varies significantly across populations, with strains from a North American population having fewerPelement insertions than strains from populations sampled in Europe or Africa. Despite these geographic differences, numbers of euchromaticPelement insertions are not strongly correlated with the degree of gonadal dysgenesis exhibited by an isofemale strain. Thus, variation inPelement insertion numbers across different populations does not necessarily lead to corresponding geographic differences in gonadal dysgenesis phenotypes. Additionally, we show that pool-seq samples can uncover population differences in the number ofPelement insertions observed from isofemale lines, but that efforts to rigorously detect differences in the number ofPelements across populations using pool-seq data must properly control for read depth per strain. Our work supports the view that euchromaticPelement copy number is not sufficient to explain variation in gonadal dysgenesis across strains ofD. melanogaster, and informs future efforts to decode the genomic basis of geographic and temporal differences inPelement induced phenotypes.
Metabolic diversity of the emerging pathogenic lineages of Klebsiella pneumoniae
Authors: Blin Camille , Passet Virginie , Touchon Marie , Rocha Eduardo P. C. , Brisse Sylvain
Published: February 2017

Multidrug resistant and hypervirulent clones of Klebsiella pneumoniae are emerging pathogens. To understand the association between genotypic and phenotypic diversity in this process, we combined genomic, phylogenomic and phenotypic analysis of a diverse set of K. pneumoniae and closely related species. These species were able to use an unusually large panel of metabolic substrates for growth, many of which were shared between all strains. We analysed the substrates used by only a fraction of the strains, identified some of their genetic basis, and found that many could not be explained by the phylogeny of the strains. Puzzlingly, few traits were associated with the ecological origin of the strains. One noticeable exception was the ability to use D‐arabinose, which was much more frequent in hypervirulent strains. The broad carbon and nitrogen core metabolism of K. pneumoniae might contribute to its ability to thrive in diverse environments. Accordingly, even the hypervirulent and multidrug resistant clones have the metabolic signature of ubiquitous bacteria. The apparent few metabolic differences between hypervirulent, multi‐resistant and environmental strains may favour the emergence of dual‐risk strains that combine resistance and hypervirulence.
Encapsulation of Beta‐carotene in Lipid Microparticles Stabilized with Hydrolyzed Soy Protein Isolate: Production Parameters, Alpha‐tocopherol Coencapsulation and Stability Under Stress Conditions
Authors: Brito‐Oliveira Thais C. , Molina Camila V. , Netto Flávia M. , Pinho Samantha C.
Published: February 2017

The objectives of this research were to study the encapsulation of beta‐carotene (BC) in solid lipid microparticles (SLM) of palm stearin (PS) and stabilized with hydrolyzed soy protein isolate (HSPI), and also to investigate the effect of alpha‐tocopherol (TOC) addition to the systems. Through the characterizations of SLM produced with different formulations, it was verified that systems with 5% (w/v) PS, 1.0% (w/v) HSPI, and 0.3% (w/v) xanthan gum (XG) presented the highest stability, with average diameters of approximately 1.2 μm. This formulation was applied for the production of BC‐loaded SLM, with different concentrations of TOC. In SLM containing TOC, nearly 75% of encapsulated BC was preserved after 45 d of storage. The kinetic profiles for degradation of encapsulated BC were fitted to a pseudo‐1st‐order model, and the results showed that the main difference among the systems with different BC:TOC ratios was the residual concentration of BC. The stability of the BC‐loaded SLMs was also studied after stress conditions, and the results showed that the SLMs were able to support thermal treatments over 60 °C but presented low stability after different ionic strength stresses.
Terrace formation in the upper Bengal basin since the Middle Pleistocene: Brahmaputra fan delta construction during multiple highstands
Authors: Pickering Jennifer L. , Goodbred Steven L. , Beam Jeremiah C. , Ayers John C. , Covey Aaron K. , Rajapara Haresh M. , Singhvi Ashok K.
Published: February 2017

Floodplains, paleosols, and antecedent landforms near the apex of the Brahmaputra fan delta in north‐central Bangladesh preserve cycles of fluvial sediment deposition, erosion and weathering. Together these landforms and their associated deposits comprise morphostratigraphic units that define the river's history and have influenced its channel position and avulsion behaviour through the Late Quaternary. Previously, temporal differentiation within these units has not been sufficient to decipher their sequence of deposition, an important step in understanding the spatial pattern of migration of the Brahmaputra River. Holocene units in this region are fairly well established by radiocarbon dating ofin situorganic material, but pre‐Holocene units are considered Pleistocene‐aged if organic material is dated >48 000 yearBP(the limit of radiocarbon dating) or the sediments are positioned beneath a prominent paleosol, interpreted as a buried soil horizon that developed during a previous sea level lowstand. In such cases, these morphostratigraphic units have been broadly interpreted as Pleistocene without knowing their absolute depositional ages or relative evolutionary chronology. Here we use detailed sediment analysis to better differentiate morphostratigraphic units at the Brahmaputra's avulsion node, establishing the sequence of deposition and subsequent weathering of these bodies. We then test this relative chronology by luminescence dating of the sands beneath these landform surfaces. This work provides the first absolute depositional age constraints of terrace sediments for the Middle to Late Pleistocene Brahmaputra River and upper Bengal basin. The luminescence ages are complemented by detailed compositional trends in the terrace deposits, including clay mineralogy and the degree of weathering. Together, these newly dated and carefully described morphostratigraphic units reflect eustasy‐driven cycles of terrace development by way of highstand floodplain deposition and subsequent lowstand exposure and weathering, along with active tectonic deformation. Defining this Late Quaternary history of terrace development and position of the Brahmaputra River is a first step toward an integrated understanding of basin and delta evolution over multiple glacioeustatic cycles and tectonically relevant timescales.
Risk factors for radiation‐induced optic neuropathy: a case–control study
Authors: Ferguson Ian , Huecker Julie , Huang Jiayi , McClelland Collin , Van Stavern Gregory
Published: February 2017

Importance

Identifying risk factors for radiation‐induced optic neuropathy (RION) could promote a more conservative approach to radiation treatment planning in vulnerable patients.

Background

This study explored possible factors beyond radiation dose associated with the development of RION after external beam radiation therapy.

Design

This was a retrospective case–control study conducted at a university hospital tertiary care center.

Participants

Cases (n = 14) meeting criteria for a diagnosis of RION by neuro‐ophthalmologic exam were identified from a single‐centre neuro‐ophthalmology database. Controls (n = 31) without RION were selected from a single‐centre radiation oncology database.

Methods

Controls were matched to cases based upon maximum radiation dose to the optic apparatus. Patient characteristics and treatment parameters were interrogated by univariate analysis for attributes predisposing to RION.

Main Outcome Measures

The primary parameter was a significant association of patient characteristics or treatment parameters with RION.

Results

Controlling for radiation dosage, no significant associations for alternative risk factors were identified.

Conclusions and Relevance

These results support the literature suggesting that the primary risk factor for developing RION is radiation dosage and that additional patient‐related and tumour‐related risk factors may play only a minor role.
Sacral nerve stimulation can alleviate symptoms of bowel dysfunction after colorectal resections
Authors: Mege D. , Meurette G. , Vitton V. , Leroi A.‐M. , Bridoux V. , Zerbib P. , Sielezneff I. ,   Club NEMO
Published: February 2017

Aim

Poor functional results, such as faecal incontinence (FI), low anterior resection syndrome (LARS) or high stool frequency, can occur after colorectal resections, including proctocolectomy with ileal pouch‐anal anastomosis (IPAA), rectal resection and left hemicolectomy. Management of such patients is problematic, and some case reports have demonstrated the effectiveness of sacral nerve stimulation (SNS) in these situations. Our aim was to analyse the effectiveness of SNS on poor functional results and on quality of life in patients after treatment with different types of colorectal resection.

Method

At five university hospitals from 2006 to 2014, patients with poor functional results after rectal resection, IPAA or left hemicolectomy underwent a staged SNS implant procedure. Failure was defined by the absence or insufficient improvement (< 50%) of FI episodes.

Results

SNS for bowel dysfunction was performed in 16 patients after rectal resection with coloanal anastomosis, left hemicolectomy with colorectal anastomosis or IPAA. Two (13%) cases of primary failure were observed after the percutaneous stimulation test. Median frequency of stool, FI episodes and urgency were significantly improved in 14 patients. Wexner and LARS scores were also significantly improved for 14 patients. When we compared results according to the type of colorectal surgery (IPAA, rectal resection or left hemicolectomy), median frequencies of stool and urgency, Wexner and LARS scores were still significantly improved. Overall success rate was 75% (12/16 patients) in intention‐to‐treat analysis and 86% (12/14 patients with permanent electrode) in per‐protocol analysis.

Conclusion

SNS seems to improve bowel dysfunction following rectal resection, left hemicolectomy or IPAA.
A systematic conservation strategy for crop wild relatives in the Czech Republic
Authors: Taylor Nigel G. , Kell Shelagh P. , Holubec Vojtěch , Parra‐Quijano Mauricio , Chobot Karel , Maxted Nigel
Published: February 2017

Aim

To create a crop wild relative (CWR) conservation strategy for the Czech Republic: the first nationalCWRconservation strategy for Central and Eastern Europe.

Location

Czech Republic.

Methods

We generated aCWRchecklist for the Czech Republic and then prioritized taxa, using widely adopted criteria modified with input from local experts, to create a nationalCWRinventory. For 204 priorityCWRspecies, we collated 206,760 presence records. We carried out spatial analyses to identify patterns in species richness, gaps in existing conservation actions, complementary conservation networks and collecting strategies to increase representativeness of gene bank accessions. We considered both specific and genetic conservation, using geographic and ecogeographic proxies for the latter.

Results

Passive in situ conservation ofCWRin the Czech Republic is comprehensive at present, with all but one priorityCWRspecies being contained in protected areas. Active in situCWRconservation could be focussed within 11 ca. 10‐km‐by‐10‐km grid cells containing 94% of priority species, or their overlapping protected areas. To augment the genetic coverage of the in situ conservation network, activeCWRconservation is encouraged within 11 supplementary areas. Meanwhile, there are huge gaps in ex situ collections, with no known conserved material for 134 of the 204 priority species. Furthermore, existing accessions are generally unrepresentative of genetic diversity.

Main conclusions

In the Czech Republic, active in situ conservation of priorityCWRshould be instigated within the 22 recommended grid cell areas or their 14 overlapping protected areas. For ex situ conservation, strategic and targeted collection of germplasm would markedly increase the value of gene bank collections. Diversity of priority CzechCWRis concentrated in South Moravia, making this a particularly importantCWRarea for the country and for Europe.
Do sea trout Salmo trutta parr surveys monitor the densities of anadromous or resident maternal origin parr, or both?
Authors: Rohtla M. , Matetski L. , Svirgsden R. , Kesler M. , Taal I. , Saura A. , Vaittinen M. , Vetemaa M.
Published: February 2017

Brown trout Salmo trutta L. parr were sampled from 21 Estonian and three Finnish streams to investigate whether national sea trout parr surveys sample the progeny of anadromous or resident maternal parents. Otolith Sr:Ca core values were used and validated as a tool for distinguishing between the progeny of the two forms. In Estonia (n = 283), 92% of the parr were the progeny of anadromous maternal parents, and 8% were the progeny of resident maternal parents, whereas in Finland (n = 24), the respective proportions were 79% and 21%. Variation in the maximum otolith Sr:Ca core values among progeny of anadromous maternal parents indicated that some adult females may enter fresh waters several months before spawning. It was concluded that easily accessible locations situated up to 30 km from the sea largely contain progeny of sea trout, whereas sites with poor connectivity with the sea can be dominated by progeny of resident trout. This study demonstrated that the method applied provided an effective means to distinguish between the progeny of sea trout and resident brown trout.
How pre‐ and postrecruitment factors shape role perceptions of European Commission officials
Authors: Trondal Jarle , Murdoch Zuzana , Geys Benny
Published: February 2017

Individuals' role perceptions are central guides to their behavior and choices as members of an organization. Understanding organizational dynamics thus requires knowledge about the determinants of such role perceptions, as well as whether—and when—organizations can influence them. This article brings forward a theoretical framework allowing for both prerecruitment (extraorganizational) and post‐recruitment (intraorganizational) determinants of individuals' role perceptions, and examines its empirical implications using a large‐N data set of temporary officials in the European Commission. We find that intergovernmental and epistemic role perceptions are strongly linked to pre‐recruitment factors (such as educational and professional background), whereas postrecruitment factors (such as length of affiliation and embeddedness within the Commission) are the main driving force behind supranational and departmental role perceptions. This heterogeneity in the importance of pre‐ and postrecruitment factors for distinct role perceptions has important consequences for conceptualizing organizational change.
The Role of Darwin in Elizabeth Grosz's Deleuzian Feminist Theory: Sexual Difference, Ontology, and Intervention
Authors: Pulkkinen Tuija
Published: February 2017

In this article on Elizabeth Grosz's philosophy and its implications for discussions about feminist theory, I first suggest that Charles Darwin plays a particular role in Grosz's recent ontological thought. This role is to provide help in joining together two incompatible sources in her work: Gilles Deleuze's monistic ontology of a constant flow of new differentiations, on the one hand, and Luce Irigaray's thought of sexual difference as the primary ontological difference, on the other. I argue that Grosz's intellectual project has developed into a grand general theory of change in which both Darwin and Irigaray are turned into ontologists in a Deleuzian vein. I then point out that Grosz's ontology also includes a political aspect, which manifests in the fact that Grosz redescribes Darwin through interpreting him primarily as a theorist of “event” and the unexpected. However, through an analysis of the discussion on Grosz between Luciana Parisi and Jami Weinstein, I speculate whether Grosz's ambition to provide a total and complete explanation of change encourages the tone of feminist discussion toward one of explanation rather than intervention.
A Dangerous Subject: The Fashion Model and the Beauty/Narcissism Double Bind
Authors: Neumann Cecilie Basberg
Published: February 2017

In the wake of modernity, women's sexuality was positioned in a way that created a beauty/narcissism double bind that is still with us today. My concern in this article is that the subject position of “fashion model” serves as a constant reminder of this split, which is directed at all women and weakens the generalized woman's political agency. Fashion models themselves experience harassment and humiliation as well as pleasure and desire in their work as fashion models. However, the small portion of feminist work that has engaged explicitly with the fashion‐model business sees it mainly as an enterprise that is alienating and hostile to women. Although I do not entirely disagree with this analysis, it neglects the meaning of beauty and what beauty does to us with regard to creativity and pleasure. I wish to explore how some of the work experience of fashion models intersects with and challenges the beauty/narcissism double bind. I suggest that rather than grounding our understanding of the subject position “fashion model” and the fashion business solely in their reinforcement of the beauty/narcissism double bind, we should pay attention to the importance of what beauty and aspects of narcissism may mean.
Availability of drug information on community pharmacy websites in Tennessee
Authors: Borja-Hart Nancy , Hohmeier Kenneth C
Published: February 2017

Objective

This study reports the availability and type of drug information resources on community pharmacy websites in Tennessee.

Methods

A list of pharmacies was obtained from the Tennessee Board of Pharmacy. All community pharmacies located in Tennessee with a website were evaluated. Community pharmacy websites that listed a drug information resource were further analysed into pharmacy type and drug information provider.

Key Findings

One hundred and sixty-nine websites were evaluated. Thirty-six websites listed a drug information resource. Fifty per cent of those sites used the drug information provider RxWiki. Other providers included drugs.com/, First Data Bank, A.D.A.M., RxList, Gold Standard Multimedia and Express Scripts.

Conclusion

Community pharmacy websites are underutilized as a provider for credible drug information for the public.
Single molecule RNA sequencing uncovers trans‐splicing and improves annotations in Anopheles stephensi
Authors: Jiang X. , Hall A. B. , Biedler J. K. , Tu Z.
Published: February 2017

Single molecule real‐time (SMRT) sequencing has recently been used to obtain full‐length cDNA sequences that improve genome annotation and reveal RNA isoforms. Here, we used one such method called isoform sequencing from Pacific Biosciences (PacBio) to sequence a cDNA library from the Asian malaria mosquito Anopheles stephensi. More than 600 000 full‐length cDNAs, referred to as reads of insert, were identified. Owing to the inherently high error rate of PacBio sequencing, we tested different approaches for error correction. We found that error correction using Illumina RNA sequencing (RNA‐seq) generated more data than using the default SMRT pipeline. The full‐length error‐corrected PacBio reads greatly improved the gene annotation of Anopheles stephensi: 4867 gene models were updated and 1785 alternatively spliced isoforms were added to the annotation. In addition, six trans‐splicing events, where exons from different primary transcripts were joined together, were identified in An. stephensi. All six trans‐splicing events appear to be conserved in Culicidae, as they are also found in Anopheles gambiae and Aedes aegypti. The proteins encoded by trans‐splicing events are also highly conserved and the orthologues of these proteins are cis‐spliced in outgroup species, indicating that trans‐splicing may arise as a mechanism to rescue genes that broke up during evolution.