bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of insulators in transgene transvection inDrosophila
Authors: Piwko Pawel , Vitsaki Ilektra , Livadaras Ioannis , Delidakis Christos
Published: March 2019

Transvection is the phenomenon where a transcriptional enhancer activates a promoter located on the homologous chromosome. It has been amply documented inDrosophilawhere homologues are closely paired in most, if not all, somatic nuclei, but it has been known to rarely occur in mammals as well. We have taken advantage of site-directed transgenesis to insert reporter constructs into the same genetic locus inDrosophilaand have evaluated their ability to engage in transvection by testing many heterozygous combinations. We find that transvection requires the presence of an insulator element on both homologues. Homotypictrans-interactions between four different insulators can support transvection: thegypsy insulator(GI),Wari, Fab-8and1A2;GIandFab-8are more effective thanWarior1A2. We show that in the presence of insulators, transvection displays the characteristics that have been previously described: it requires homologue pairing, but can happen at any of several loci in the genome; a solitary enhancer confronted with an enhancerless reporter is sufficient to drive transcription; it is weaker than the action of the same enhancer-promoter pair incisand it is further suppressed bycis-promoter competition. Though necessary, the presence of homotypic insulators is not sufficient for transvection; their position, number and orientation matters. A single GI adjacent to both enhancer and promoter is the optimal configuration. The addition of a heterologous insulator in one homolog can positively or negatively influence transvection strength. The local landscape of enhancers and promoters is also important, indicative of complex insulator-enhancer-promoter interactions.
Hierarchical clustering of gene-level association statistics reveals shared and differential genetic architecture among traits in the UK Biobank
Authors: McGuirl Melissa R. , Pattillo Smith Samuel , Sandstede Björn , Ramachandran Sohini
Published: March 2019

Genome-wide association (GWA) studies have generally focused on a single phenotype of interest. Emerging biobanks that pair genotype data from thousands of individuals with phenotype data using medical records or surveys enable testing for genetic associations in each phenotype assayed. However, methods for characterizing shared genetic architecture among multiple traits are lagging behind. Here, we present a new method, Ward clustering to identify Internal Node branch length outliers using Gene Scores (WINGS), for characterizing shared and divergent genetic architecture among multiple phenotypes. The objective of WINGS (freely available athttps://github.com/ramachandran-lab/PEGASUS-WINGS) is to identify groups of phenotypes, or “clusters”, that share a core set of genes enriched for mutations in cases. We show in simulations that WINGS can reliably detect phenotype clusters across a range of percent shared architecture and number of phenotypes included. We then use the gene-level association test PEGASUS with WINGS to characterize shared genetic architecture among 87 case-control and seven quantitative phenotypes in 349,468 unrelated European-ancestry individuals from the UK Biobank. We identify 10 significant phenotype clusters that contain two to eight phenotypes. One significant cluster of seven immunological phenotypes is driven by seven genes; these genes have each been associated with two or more of those same phenotypes in past publications. WINGS offers a precise and efficient new application of Ward hierarchical clustering to generate hypotheses regarding shared genetic architecture among phenotypes in the biobank era.
Shifted distribution baselines: neglecting long-term biodiversity records risks overlooking potentially suitable habitat for conservation management
Authors: Monsarrat Sophie , Novellie Peter , Rushworth Ian , Kerley Graham
Published: March 2019

Setting appropriate conservation measures to halt the loss of biodiversity requires a good understanding of species’ habitat requirements and potential distribution. Recent (past few decades) ecological data are typically used to estimate and understand species’ ecological niche. However, historical local extinctions may have truncated species-environment relationships, resulting in a biased perception of species’ habitat preferences. This may result in incorrect assessments of the area potentially available for their conservation. Incorporating long-term (centuries-old) occurrence records with recent records may provide better information on species-environment relationships and improve the modeling and understanding of habitat suitability. We test whether neglecting long-term occurrence records leads to an underestimation of species’ historical niche and potential distribution and identify which species are more vulnerable to this effect. We compare outputs of species distribution models and niche hypervolumes built using recent records only with those built using both recent and long-term (post-1500) records, for a set of 34 large mammal species in South Africa. We find that, while using recent records only is adequate for some species, adding historical records in the analyses impacts estimates of the niche and habitat suitability for fourteen species (41%) in our dataset, and that this effect is significantly higher for carnivores. These results show that neglecting long-term biodiversity records in spatial analyses risks misunderstanding, and generally underestimating, species’ niche, which in turn may lead to ill-informed management decisions, with significant implications for the effectiveness of conservation efforts.
The nonlinear structure of linkage disequilibrium
Authors: Smith Reginald D.
Published: March 2019

The allele frequency dependence of the ranges of all measures of linkage disequilibrium is well-known. The maximum values of commonly used parameters such asr2andDvary depending on the allele frequencies at each locus. However, though this phenomenon is recognized and accounted for in many studies, the comprehensive mathematical framework underlying the limits of linkage disequilibrium measures at various frequency combinations is often heuristic or empirical. Here, it is demonstrated that underlying this behavior is the fundamental shift between linear and nonlinear dependence in the linkage disequilibrium structure between loci. The proportion of linear and nonlinear dependence can be estimated and it demonstrates how even the same values ofr2can have different implications for the nature of the overall dependence. One result of this is the value ofD′, when defined as only a positive number, has a minimum value of |r|. Understanding this dependence is crucial to making correct inferences about the relationships between two loci in linkage disequilibrium.
A Novel and Efficient Approach for Screening Cancer Cell Specific Monoclonal Antibodies
Authors: Pei Xin-Hui
Published: March 2019

Cancer cell specific antibodies are pivotal tools in developing new immunotherapies for treating cancers. However, acquirement of cancer cell specific antibodies is time-consuming and often arduous. To circumvent such a barrier, we developed a novel antibody-screening method that can be used to efficiently produce cancer cell specific antibodies by an ‘antibody filter’ mechanism. First, we used normal human cells to perform the immunization in mice and collected the antisera. Second, we used human cancer cells together with the antisera against normal human cells to immunize another batch of mice. Theoretically, the antisera were able to neutralize the antigens from normal human cells, and therefore specific antigens only expressed in cancer cells could take advantage of the immunization. Third, we screened positive clones that are specific for cancer cells but not normal cells. Using this conceptual method, we successfully obtained 11 monoclonal antibodies that are specific for a human liver cancer cells line (HepG2) but not for a normal human liver cell line (HH). In addition, these clones failed to recognize other human cancer cells originated from different tissues, further highlighting the specificity. Collectively, we provide a novel and effective approach for screening cancer cell specific monoclonal antibodies, which may significantly facilitate the development of new anti-cancer therapeutics.
Complex polymorphic genetic architecture underlies trans-regulatory variation among strains of Saccharomyces cerevisiae
Authors: Metzger Brian P. H. , Wittkopp Patricia J.
Published: March 2019

Heritable variation in gene expression is common within species. Much of this variation is due to genetic changes at loci other than the affected gene and is thus trans-acting. This trans-regulatory variation is often polygenic, with individual variants typically having small effects, making the genetic architecture of trans-regulatory variation challenging to study. Consequently, key questions about trans-regulatory variation remain, including how selection affects this variation and how trans-regulatory variants are distributed throughout the genome and within species. Here, we show that trans-regulatory variation affecting TDH3 promoter activity is common among strains of Saccharomyces cerevisiae. Comparing this variation to neutral models of trans-regulatory evolution based on empirical measures of mutational effects revealed that stabilizing selection has constrained this variation. Using a powerful quantitative trait locus (QTL) mapping method, we identified ∼100 loci altering expression between a reference strain and each of three genetically distinct strains. In all three cases, the non-reference strain alleles increased and decreased TDH3 promoter activity with similar frequencies, suggesting that stabilizing selection maintained many trans-acting variants with opposing effects. Loci altering expression were located throughout the genome, with many loci being strain specific and others being shared among multiple strains. These findings are consistent with theory showing stabilizing selection for quantitative traits can maintain many alleles with opposing effects, and the wide-spread distribution of QTL throughout the genome is consistent with the omnigenic model of complex trait variation. Furthermore, the prevalence of alleles with opposing effects might provide raw material for compensatory evolution and developmental systems drift.

Significance statement

Gene expression varies among individuals in a population due to genetic differences in regulatory components. To determine how this variation is distributed within genomes and species, we used a powerful genetic mapping approach to examine multiple strains of Saccharomyces cerevisiae. Despite evidence of stabilizing selection maintaining gene expression levels among strains, we find hundreds of loci that affect expression of a single gene. These loci vary among strains and include similar frequencies of alleles that increase and decrease expression. As a result, each strain contains a unique set of compensatory alleles that lead to similar levels of gene expression among strains. This regulatory variation might form the basis for large scale regulatory rewiring observed between distantly related species.
Dynamics and Internal Control of Body Temperature in Response to Infectious Agents and Other Causal Factors
Authors: Schaper Charles D.
Published: March 2019

Thermoregulation is crucial to homeostasis, but the mechanisms of its dysfunction are still largely mysterious, including fever, which is generally the most disconcerting sign of a serious infection or disease. Theories on body temperature dynamics that aim to explain a fever, such as changes in an internal setpoint, have been proposed, but none can identify the fundamental molecular pathways that produce a fever. Here, potential molecular pathways resultant in fever are identified, modeled, and compared to experimental temperature response data. Based on recent developments made by this lab, which has shown that the pyrogen prostaglandin E2 (PGE2) possesses similar binding affinity as the hormone cortisol (CORT) at the critical ligand binding domain (LBD) of glucocorticoid receptors (GR); molecular modeling, mathematical modeling and a case study for validation is used to indicate that competitive inhibition of CORT by PGE2 as a fundamental reason for dysfunctional dynamics of body temperature, including fever. Comprised of a superposition of proportional and derivative terms of signals representing temperature receptors, CORT concentration, and PGE2 concentration, the internal temperature control model characterizes dynamics associated with the cardiovascular, immune, and neural systems in response to infectious agents, triggering events, and other causal factors. The model is validated by examination of the transient and spectral characteristics of a three-day case history involving temperature trajectories after physical activity protocols in response to a standard vaccination of pneumococcal and influenza species.
Genes essential for embryonic stem cells are associated with neurodevelopmental disorders
Authors: Shohat Shahar , Shifman Sagiv
Published: March 2019

Mouse embryonic stem cells (mESCs) are a key component in generating mouse models for human diseases and performing basic research on pluripotency, but how many genes are essential for mESCs is still unknown. We performed a genome-wide screen for essential genes in mESCs and compared it to human cells. We found that essential genes are enriched for basic cellular functions, are highly expressed in mESCs, and tend to lack paralog genes. Notably, we discovered that genes that are essential specifically in mESCs play a role in pathways associated with their pluripotent state. We show that 25% of human genes that are intolerant to loss-of-function mutations are essential in mouse or human ESCs and that the human phenotypes most significantly associated with essential genes are neurodevelopmental. Our results provide insights into essential genes in the mouse, the pathways which govern pluripotency, and suggest that many genes associated with neurodevelopmental disorders are essential at very early embryonic stages.
Major QTLs for resistance to early and late leaf spot diseases are identified on chromosomes 3 and 5 in peanut (Arachis hypogaea)
Authors: Chu Ye , Chee Peng , Culbreath Albert , Isleib Tom G. , Holbrook Corley C. , Ozias-Akins Peggy
Published: March 2019

Early and late leaf spots are the major foliar diseases of peanut responsible for severely decreased yield in the absence of intensive fungicide spray programs. Pyramiding host resistance to leaf spots in elite cultivars is a sustainable solution to mitigate the diseases. In order to determine the genetic control of leaf spot disease resistance in peanut, a recombinant inbred line population (Florida-07 x GP-NC WS16) segregating for resistance to both diseases was used to construct a SNP-based linkage map consisting of 855 loci. QTL mapping revealed three resistance QTLs for late leaf spot qLLSA05 (phenotypic variation explained, PVE=7-10%), qLLSB03 (PVE=5-7%), and qLLSB05 (PVE=15-41%) that were consistently expressed over multi-year analysis. Two QTL, qLLSA05 and qLLSB05, confirmed our previously published QTL-seq results. For early leaf spot, three resistance QTLs were identified in multiple years, two on chromosome A03 (PVE=8-12%) and one on chromosome B03 (PVE=13-20%), with the locus qELSA03_1.1 coinciding with the previously published genomic region for LLS resistance in GPBD4. Comparative analysis of the genomic regions spanning the QTLs suggests that resistance to early and late leaf spots are largely genetically independent. In addition, QTL analysis on yield showed that the presence of resistance allele in qLLSB03 and qLLSB05 loci might result in protection from yield loss caused by LLS disease damage. Finally, post hoc analysis of the RIL subpopulation that was not utilized in the QTL mapping revealed that the flanking markers for these QTLs can successfully select for resistant and susceptible lines, confirming the effectiveness of pyramiding these resistance loci to improve host-plant resistance in peanut breeding programs using marker-assisted selection.
The reactivity of an unusual amidase may explain colibactin’s DNA cross-linking activity
Authors: Jiang Yindi , Stornetta Alessia , Villalta Peter W. , Wilson Matthew R. , Boudreau Paul D. , Zha Li , Balbo Silvia , Balskus Emily P.
Published: March 2019

Certain commensal and pathogenic bacteria produce colibactin, a small molecule genotoxin that causes interstrand cross-links in host cell DNA. Though colibactin has been found to alkylate DNA, the molecular basis for cross-link formation is unclear. Here, we report that the colibactin biosynthetic enzyme ClbL is an amide bond-forming enzyme that links aminoketone and β-keto thioester substrates in vitro and in vivo. The substrate specificity of ClbL strongly supports a role for this enzyme in terminating the colibactin NRPS-PKS assembly line. This transformation would incorporate two electrophilic cyclopropane warheads into the final natural product scaffold. Overall, this work provides a biosynthetic explanation for colibactin’s DNA crosslinking activity and paves the way for further study of its chemical structure.
Induction of the nicotinamide riboside kinase NAD+ salvage pathway in skeletal myopathy of H6PDH KO mice
Authors: Doig Craig L. , Zielinska Agnieszka E. , Fletcher Rachel S. , Oakey Lucy A. , Elhassan Yasir S. , Garten Antje , Cartwright David , Heising Silke , Alsheri Ahmed , Watson David G. , Adamski Jerzy , Tennant Daniel A. , Lavery Gareth G.
Published: March 2019

Background

Hexose-6-Phosphate Dehydrogenase (H6PDH) is a generator of NADPH in the Endoplasmic/Sarcoplasmic Reticulum (ER/SR). Interaction of H6PDH with 11β-hydroxysteroid dehydrogenase type 1 provides NADPH to support oxo-reduction of inactive to active glucocorticoids, but the wider understanding of H6PDH in ER/SR NAD(P)(H) homeostasis is incomplete. Muscle specific lack of H6PDH results in a deteriorating skeletal myopathy, altered glucose homeostasis, ER stress and activation of the unfolded protein response. Here we further assess muscle responses to H6PDH deficiency to delineate pathways that may underpin myopathy and link SR redox status to muscle wide metabolic adaptation.

Methods

We analysed skeletal muscle from H6PDH knockout (H6PDKO), H6PDH and NRK2 double knockout (DKO) and wild-type (WT) mice. H6PDKO mice were supplemented with the NAD+ precursor nicotinamide riboside. Skeletal muscle samples were subject to biochemical analysis including NAD(H) measurement, LC/MS based metabolomics, Western immunoblotting, and high resolution mitochondrial respirometry. Genetic and supplement models were assessed for degree of myopathy compared to H6PDKO.

Results

H6PDKO skeletal muscle showed adaptations in the routes regulating nicotinamide and NAD+ biosynthesis, with significant activation of the Nicotinamide Riboside Kinase 2 (NRK2) pathway. Associated with changes in NAD+ biosynthesis H6PDKO muscle had impaired mitochondrial respiratory capacity with altered mitochondrial acylcarnitine and acetyl CoA metabolism. Boosting NAD+ levels through the NRK2 pathway using the precursor nicotinamide riboside had no effect to mitigate ER stress and dysfunctional mitochondrial respiratory capacity or Acetyl-CoA metabolism. Similarly, H6PDKO/NRK2 double KO mice did not display an exaggerated timing or severity of myopathy or overt change in mitochondrial metabolism despite depression of NAD+ availability.

Conclusions

These findings suggest a complex metabolic response to changes to muscle SR NADP(H) redox status that result in impaired mitochondrial energy metabolism and activation of cellular NAD+ salvage pathways. It is possible that SR can sense and signal perturbation in NAD(P)(H) that cannot be rectified in the absence of H6PDH. Whether NRK2 pathway activation is a direct response to changes in SR NAD(P)(H) availability or adaptation to deficits in metabolic energy availability remains to be resolved.
Rapid, precise, and reliable measurement of delay discounting using a Bayesian learning algorithm
Authors: Ahn Woo-Young , Gu Hairong , Shen Yitong , Haines Nathaniel , Hahn Hunter A. , Teater Julie E. , Myung Jay I. , Pitt Mark A.
Published: March 2019

Machine learning has the potential to facilitate the development of computational methods that improve the measurement of cognitive and mental functioning. In three populations (college students, patients with a substance use disorder, and Amazon Mechanical Turk workers), we evaluated one such method, Bayesian adaptive design optimization (ADO), in the area of delay discounting by comparing its test-retest reliability, precision, and efficiency with that of a conventional staircase method. In all three populations tested, the results showed that ADO led to 0.95 or higher test-retest reliability of the discounting rate within 10-20 trials (under 1-2 minutes of testing), captured approximately 10% more variance in test-retest reliability, was 3-5 times more precise, and was 3-8 times more efficient than the staircase method. The ADO methodology provides efficient and precise protocols for measuring individual differences in delay discounting.
Modulation of Flagellar Rotation in Surface-Attached Bacteria: A Circuit for Rapid Surface-Sensing
Authors: Schniederberend Maren , Johnston Jessica F. , Shine Emilee , Shen Cong , Jain Ruchi , Emonet Thierry , Kazmierczak Barbara I.
Published: March 2019

Attachment is a necessary first step in bacterial commitment to surface-associated behaviors that include colonization, biofilm formation, and host-directed virulence. The Gram-negative opportunistic pathogenPseudomonas aeruginosacan initially attach to surfaces via its single polar flagellum. Although many bacteria quickly detach, some become irreversibly attached and express surface-associated structures, such as Type IV pili, and behaviors, including twitching motility and biofilm initiation.P. aeruginosathat lack the GTPase FlhF assemble a randomly placed flagellum that is motile; however, we observed that these mutant bacteria show defects in biofilm formation comparable to those seen for non-motile, aflagellate bacteria. This phenotype was associated with altered behavior of ΔflhFbacteria immediately following surface-attachment. Forward and reverse genetic screens led to the discovery that FlhF interacts with FimV to control flagellar rotation at a surface, and implicated cAMP signaling in this pathway. Although cAMP controls many transcriptional programs inP. aeruginosa, the known targets of this second messenger were not required to modulate flagellar rotation in surface-attached bacteria. Instead, alterations in switching behavior of the motor appear to result from previously undescribed effects of cAMP on switch complex proteins and/or the motor-stators associated with them.

Author Summary

Attachment to a surface often triggers programs of gene expression that alter the behavior, virulence and fitness of bacteria. Initial contact is usually mediated by surface exposed adhesins, such as flagella or pili/fimbriae, and there is much interest in how these structures might sense and respond to surface attachment. The human bacterial pathogenPseudomonas aeruginosausually contacts surfaces via its polar flagellum, the rotary motor that also powers bacterial swimming. We observed that wild-type bacteria quickly stopped rotating their flagellum after surface attachment, but that a mutant lacking the flagellar-associated protein FlhF did not. Using a combination of genetic approaches, we demonstrated that FlhF interacts with a component of the flagellar rotor (FliG) and with a polar scaffolding protein that positively regulates cAMP production (FimV) to stop flagellar rotation and thereby favor bacterial persistence at a surface. We provide evidence that the second messenger cAMP is the likely signal generated by flagellar-mediated surface attachment and show that cAMP is sufficient to alter the behavior of the flagellar motor.
Bioisosterism reveals new structure-odor relationships
Authors: Tahirova Narmin , Poivet Erwan , Xu Lu , Peterlin Zita , Zou Dong-Jing , Firestein Stuart
Published: March 2019

The question of structure-odor relationship (SOR) has inspired numerous studies into chemical odorants via their perceptual similarities. Much of this data comes from psychophysical studies on humans, precluding the possibility of direct measurements of receptor or receptor neuron activation. Remarkably, we find that many of the perceptual classifications used by human subjects translate well enough to mouse that we can apply cellular methods to better understand the molecular mechanism, that leads to odor discrimination and perception. Using a well studied and well recognizable odor percept of bitter almond, we have tested an odorant panel of aldehydes and ketones that were reported to share such perceptual qualities. These odorants include aromatic and aliphatic, as well as cyclic and allylic features. When parsing these odorants using chemical descriptors, we have a clear separation of molecules possessing these various features. However, here we show that OSN responses better recapitulate the physiological percept. Using these odorants, we also provide a proof-of-concept for non-classical bioisosterism at work in the olfactory system.
Clustering co-abundant genes identifies components of the gut microbiome that are reproducibly associated with colorectal cancer and inflammatory bowel disease
Authors: Minot Samuel S. , Willis Amy D.
Published: March 2019

Background

Whole-genome “shotgun” (WGS) metagenomic sequencing is an increasingly widely used tool for analyzing the metagenomic content of microbiome samples. While WGS data contains gene-level information, it can be challenging to analyze the millions of microbial genes which are typically found in microbiome experiments. To mitigate the ultrahigh dimensionality challenge of gene-level metagenomics, it has been proposed to cluster genes by co-abundance to form Co-Abundant Gene groups (CAGs). However, exhaustive co-abundance clustering of millions of microbial genes across thousands of biological samples has previously been intractable purely due to the computational challenge of performing trillions of pairwise comparisons.

Results

Here we present a novel computational approach to the analysis of WGS datasets in which microbial gene groups are the fundamental unit of analysis. We use the Approximate Nearest Neighbor heuristic for near-exhaustive average linkage clustering to group millions of genes by co-abundance. This results in thousands of high-quality CAGs representing complete and partial microbial genomes. We applied this method to publicly available WGS microbiome surveys and found that the resulting microbial CAGs associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC) were highly reproducible and could be validated independently using multiple independent cohorts.

Conclusions

This powerful approach to gene-level metagenomics provides a powerful path forward for identifying the biological links between the microbiome and human health. By proposing a new computational approach for handling high dimensional metagenomics data, we identified specific microbial gene groups that are associated with disease that can be used to identify strains of interest for further preclinical and mechanistic experimentation.
Characterizing the nuclear and cytoplasmic transcriptomes in developing and mature human cortex uncovers new insight into psychiatric disease gene regulation
Authors: Price Amanda J. , Hwang Taeyoung , Tao Ran , Burke Emily E. , Rajpurohi Anandita , Shin Joo Heon , Hyde Thomas M. , Kleinman Joel E. , Jaffe Andrew E. , Weinberger Daniel R.
Published: March 2019

Transcriptome compartmentalization by the nuclear membrane provides both stochastic and functional buffering of transcript activity in the cytoplasm and has recently been implicated in neurodegenerative disease processes. Although many mechanisms regulating transcript compartmentalization are also prevalent in brain development, the extent to which subcellular localization differs as the brain matures has yet to be addressed. To characterize the nuclear and cytoplasmic transcriptomes during brain development, we sequenced both RNA fractions from homogenate prenatal and adult human postmortem cortex using PolyA+ and RiboZero library preparation methods. We find that while many genes are differentially expressed by fraction and developmental expression changes are similarly detectable in nuclear and cytoplasmic RNA, the compartmented transcriptomes become more distinct as the brain matures, perhaps reflecting increased utilization of nuclear retention as a regulatory strategy in adult brain. We examined potential mechanisms of this developmental divergence including alternative splicing, RNA editing, nuclear pore composition, RNA binding protein motif enrichment, and RNA secondary structure. Intron retention is associated with greater nuclear abundance in a subset of transcripts, as is enrichment for several splicing factor binding motifs. Finally, we examined disease association with fraction-regulated gene sets and found nuclear-enriched genes were also preferentially enriched in gene sets associated with neurodevelopmental psychiatric diseases. These results suggest that although gene-level expression is globally comparable between fractions, nuclear retention of transcripts may play an underappreciated role in developmental regulation of gene expression in brain, particularly in genes whose dysregulation is related to neuropsychiatric disorders.
Plant-soil feedback contributes to predicting plant invasiveness of 68 alien plant species differing in invasive status
Authors: Aldorfová Anna , Knobová Pavlína , Münzbergová Zuzana
Published: March 2019

1. Understanding what species characteristics allow some alien plants to become invasive while others fail to is critical to our understanding of community assembly processes. While many characteristics have been shown to predict plant invasiveness, the importance of plant-soil feedbacks (PSFs) in invasions has been difficult to assess since individual studies include only a few species and use disparate methodology.

2. We studied PSFs of 68 invasive and non-invasive alien species in a single two-phase garden experiment, and compared the relative importance of PSF, residence time, phylogenetic novelty and plant traits for plant invasiveness. Additionally, we tested for relationships between PSF, residence time and phylogenetic novelty.

3. PSF for seedling establishment belonged to five best predictors of plant invasiveness, along with specific leaf area, height, seedling growth rate, and residence time. Invasive species had more positive PSF for seedling establishment, but not for biomass, than non-invasive species. Phylogenetically novel species experienced less negative PSF than species with native congeners, suggesting they benefit more from enemy release. PSF of non-invasive species, contrary to that of invasive species, was becoming more negative with increasing residence time.

4.Synthesis. We demonstrated that PSF plays a role in predicting invasiveness that is comparable with other species characteristics that are more commonly studied. PSF should thus receive more attention in studies predicting community structure and in programs assessing the likely invasions of aliens.
Production of nonnatural straight-chain amino acid 6-aminocaproate via an artificial iterative carbon-chain-extension cycle
Authors: Cheng Jie , Song Tingting , Wang Huayu , Zhou Xiaohua , Torrens-Spence Michael P. , Wang Dan , Weng Jing-Ke , Wang Qinhong
Published: March 2019

Bioplastics produced from microbial source are promising green alternatives to traditional petrochemical-derived plastics. Nonnatural straight-chain amino acids, especially 5-aminovalerate, 6-aminocaproate and 7-aminoheptanoate are potential monomers for the synthesis of polymeric bioplastics as their primary amine and carboxylic acid are ideal functional groups for polymerization. Previous pathways for 5-aminovalerate and 6-aminocaproate biosynthesis in microorganisms are derived from L-lysine catabolism and citric acid cycle, respectively. Here, we show the construction of an artificial iterative carbon-chain-extension cycle inEscherichia colifor simultaneous production of a series of nonnatural amino acids with varying chain length. Overexpression of L-lysine α-oxidase inE. coliyields 2-keto-6-aminocaproate as a non-native substrate for the artificial iterative carbon-chain-extension cycle. The chain-extended α-ketoacid is subsequently decarboxylated and oxidized by an α-ketoacid decarboxylase and an aldehyde dehydrogenase, respectively, to yield the nonnatural straight-chain amino acid products. The engineered system demonstrated simultaneousin vitroproduction of 99.16 mg/L of 5-aminovalerate, 46.96 mg/L of 6-aminocaproate and 4.78 mg/L of 7-aminoheptanoate after 8 hours of enzyme catalysis starting from 2-keto-6-aminocaproate as the substrate. Furthermore, simultaneous production of 2.15 g/L of 5-aminovalerate, 24.12 mg/L of 6-aminocaproate and 4.74 mg/L of 7-aminoheptanoate was achieved in engineeredE. coli. This work illustrates a promising metabolic-engineering strategy to access other medium-chain organic acids with -NH2,-SCH3, -SOCH3, -SH, -COOH, -COH, or -OH functional groups through carbon-chain-elongation chemistry.
Towards a further understanding of measles vaccine hesitancy in Khartoum state, Sudan: A qualitative study
Authors: Sabahelzain Majdi M. , Moukhyer Mohamed , Dubé Eve , Hardan Ahmed , Bosma Hans , van den Borne Bart
Published: March 2019

Background

Vaccine hesitancy is one of the contributors to low vaccination coverage in both developed and developing countries. Sudan is one of the countries that suffers from low measles vaccine coverage and from measles outbreaks. For a further understanding of measles vaccine hesitancy in Sudan, this study aimed at exploring the opinions of Expanded Program on Immunization officers at ministries of health, WHO, UNICEF and vaccine care providers at Khartoum-based primary healthcare centers.

Methods

Qualitative data were collected using semi-structured interviews during the period January-March 2018. The topic list for the interviews was developed and analyzed using the framework “Determinants of Vaccine Hesitancy Matrix” that developed by the WHO-SAGE Working Group.

Findings

The interviews were conducted with 14 participants. The majority of participants confirmed the existence of measles vaccine hesitancy in Khartoum state. They further identified various determinants that grouped into three domains including contextual, groups and vaccination influences. The main contextual determinant as reported is the presence of “anti-vaccination”; who mostly belong to some religious and ethnic groups. Parents’ beliefs about prevention and treatment from measles are the main determinants of the group influences. Attitude of the vaccine providers, measles vaccine schedule and its mode of delivery were the main vaccine related determinants.

Conclusion

Measles vaccine hesitancy in Sudan appears complex and highly specific to local circumstances. To better understand the magnitude and the context-specific causes of measles vaccine hesitancy and to develop adapted strategies to address them, there is a need to investigate measles vaccine hesitancy among parents.
Crystal structures of binuclear complexes of gadolinium(III) and dysprosium(III) with oxalate bridges and chelating N,N′-bis(2-oxidobenzyl)-N,N′-bis(pyridin-2-ylmethyl)ethylenediamine (bbpen2−)
Authors: Barbosa Guilherme Augusto , Santana Francielli Sousa , Nunes Giovana Gioppo , Soares Jaísa Fernandes
Published: March 2019

The reaction between mononuclear [Ln(bbpen)Cl] [Ln = Gd or Dy; H2bbpen = N,N′-bis(2-hydroxybenzyl)-N,N′-bis(pyridin-2-ylmethyl)ethylenediamine, C28H30N4O2] and potassium oxalate monohydrate in water/methanol produced the solvated centrosymmetric isostructural binuclear (μ-oxalato)bis{[N,N′-bis(2-oxidobenzyl-κO)-N,N′-bis(pyridin-2-ylmethyl-κN)ethylenediamine-κ2
N,N′]dilanthanide(III)}–methanol–water (1/4/4) complexes, [Ln
2(C28H28N4O2)2(C2O4)]·4CH3OH·4H2O, with lanthanide(III) = gadolinium(III) (Ln = Gd) and dysprosium(III) (Ln = Dy), in high yields (ca 70%) directly from the reaction mixtures. In both complexes, the lanthanide ion is eight-coordinate and adopts a distorted square-antiprismatic coordination environment. The triclinic (P\overline{1}) unit cell contains one dimeric unit together with four water and four methanol molecules; in the final structural model, two of each type of solvating molecule refine well. In each lanthanide(III) dimeric molecule, the medium-strength O...H—O hydrogen-bonding pattern involves four oxygen atoms, two of them from the phenolate groups that are `bridged' by one water and one methanol molecule. These interactions seem to contribute to the stabilization of the relatively compact shape of the dimer. Electron densities associated with an additional water and methanol molecule were removed with the SQUEEZE procedure in PLATON [Spek (2015). Acta Cryst. C71, 9–18]. These two new compounds are of interest with respect to magnetic properties.
Managing formal institutional challenges when entering Cuba
Authors: Rottig Daniel , Muscarella Sebastian , Torres de Oliveira Rui
Published: March 2019

Purpose

The purpose of this paper is to analyze the formal political, legal and economic institutional legitimacy challenges for (US-based) multinational corporations (MNCs) attempting to enter the Cuban market, discuss the key local constituencies in Cuba that are able to grant legitimacy and sketch out respective strategies to deal with each of these formal institutional challenges.

Design/methodology/approach

A qualitative research approach comprising semi-structured executive interviews was used, combined with the analysis of media accounts and recent governmental policies and developments. The authors interpreted the gathered data and information based on institutional theory.

Findings

This paper sketches out specific legitimacy challenges for (US-based) MNCs when entering Cuba and discusses strategies to manage these challenges.

Research limitations/implications

The authors provide an application of institutional theory in the specific context of Cuba and so demonstrate the value of applying this theoretical lens to better understand the local legitimacy processes in this particular emerging market environment.

Practical implications

This study presents a framework of strategies (US-based) MNCs may use to inform their entry strategies into the Cuban market, based on an analysis of the local institutional environment, legitimacy pressures and constituencies able to grant or withdraw the approval and support of foreign MNCs.

Originality/value

This paper is an original application of institutional theory to the emerging market of Cuba using a qualitative research approach, and so contributes to an emerging stream of research studying this market context from an academic and practical perspective.
Corporate social responsibility of Islamic and conventional banks
Authors: Aracil Elisa
Published: March 2019

Purpose

The purpose of this paper is to compare the sustainability practices of Islamic and conventional banks, with the aim of evaluating whether their Corporate Social Responsibility (CSR) strategies converge or diverge in response to formal and informal institutions in an emerging country.

Design/methodology/approach

Drawing on institutional theory, this study contextualizes the competitive scenario through the National Business System (NBS) framework, and showcases the CSR strategies employed by large conventional and Islamic banks in Turkey. CSR patterns are examined from different angles such as motivations, strategy, actions and institutional results.

Findings

Within the same institutional environment, Islamic and non-Islamic banks combine convergent and divergent models to accommodate institutional realities in their CSR policies. Islamic banks exhibit an implicit commitment to CSR that is mostly based on informal institutions, whereas conventional banks use explicit CSR strategies as a means to fill the voids in formal institutions. In addition, philanthropy-oriented CSR prevails in Islamic banks, as opposed to the CSR actions associated with core business that are followed by conventional banks.

Social implications

An increased focus on formal institutions and explicit CSR actions by Islamic banks may further contribute to social well-being in emerging countries.

Originality/value

This study contributes to the paucity of research, from an institutional perspective, related to CSR practices amongst Islamic and conventional banks in emerging countries.
Are the early benefits of the Adoption Support Fund (therapeutic support for adoptive families) sustainable?
Authors: King Sadie , Gieve Matt , Iacopini Giorgia , Hahne Anna Sophie , Stradling Heather
Published: March 2019

Purpose

The purpose of this paper is to explore the wider context in which the national evaluation of the Adoption Support Fund (ASF) was delivered and raise concerns about the sustainability of the early outcomes.

Design/methodology/approach

The paper briefly summarises the outcomes of a two-year mixed-methods evaluation. This included a two-wave postal survey (n=792) and follow-up (n=481), an online survey of adopters (n=586) and professionals (providers n=50, local authority staff n=124) and in-depth family interviews. The focus of the discussion on sustainability is drawn from the qualitative research of 10 local authority case studies based on 86 interviews with adoption teams and 33 providers and the perspectives of parents.

Findings

Whilst the ASF showed modest early outcomes for families in terms of improved mental health and wellbeing without the scaffolding of wider support of services able to understand the complex lifelong needs of adoptive children and their families, the sustainability of the benefits of therapeutic support is questioned. Adoption teams struggled with the increased burden of administration of the fund, their knowledge of therapeutic interventions, an evidence base and quality of provision from a market that is difficult to regulate. In a society that is failing to meet the mental health and wellbeing needs of children generally, how can a single intervention meet the needs of a very vulnerable group?

Research limitations/implications

Research and evaluation on interventions in children’s social care could be more systems aware and instead of narrowly focusing on outcomes pay attention to the complex network of services that interlink to support vulnerable children and their families and the restraints on resources that they are working with.

Social implications

To prevent adoption breakdown and increase recruitment of adopters, support for adoptive families needs to be improved beyond the current scope of the ASF. A wide range of services are required to support adopted children particularly as they grow into adolescence. While families have the right to live independently of social services, the awareness of their needs throughout public organisations should be raised particularly in schools.

Originality/value

This paper represents the views of the evaluators at TIHR of the ASF beyond the scope of the original evaluation. It reflects on the wider context of the role out of the Fund and raises important questions about the failure to support the mental health and wellbeing needs of the most vulnerable children in society. It is an organisation reflection drawing on early research in children’s social care from its archive.
Compounding human stressors cause major regeneration debt in over half of eastern US forests
Authors: Miller Kathryn M. , McGill Brian J.
Published: March 2019

The future of temperate forests in the face of global change and anthropogenic stressors remains uncertain. The regeneration stage, which is a critical bottleneck for many organisms, is a key indicator of forest health, future canopy composition and forest adaptive capacity.

In trees, seemingly healthy forests can be at long‐term risk due to insufficient juveniles to replace them (regeneration failure), or compositional differences between juveniles and adults (regeneration mismatch). We propose ‘regeneration debt’ to collectively describe regeneration failure and mismatch in analogy to extinction debt. To demonstrate this concept, we conducted a macroecological analysis of regeneration debt and anthropogenic stressors in eastern US forests.

Using U.S. Forest Service‐Forest Inventory and Analysis data, we quantified regeneration debt in 18 states from Maine to South Carolina, and evaluated the influence of site, anthropogenic stressors and climate drivers in the most affected regions.

We identified three distinct regions, with little debt in the north, moderate debt in the south and severe regeneration debt in the central, mid‐Atlantic region. In this region, multiple anthropogenic stressors (invasive plants, deer overabundance and land use) were associated with both low‐regeneration abundance and the prevalence of disease‐prone and/or suboptimal species.

Synthesis and applications. Without management intervention, the severe regeneration debt in the mid‐Atlantic region will likely lead to long‐term declines in forest cover, with cascading negative effects on forest‐dependent taxa and ecosystem services. Moreover, the location of the regeneration debt, which is at the northern edge of and involves many of the tree species that are predicted to gain suitable habitat in the Northeastern US, has consequences that extend far beyond its current geographic extent. In fact, this regeneration debt may already be functioning as a barrier to poleward tree migration. Our results demonstrate the value of regeneration debt as an indicator of ecosystem health and forest adaptive capacity.
Diatoms shape the biogeography of heterotrophic prokaryotes in early spring in the Southern Ocean
Authors: Liu Yan , Debeljak Pavla , Rembauville Mathieu , Blain Stéphane , Obernosterer Ingrid
Published: March 2019

The interplay among microorganisms profoundly impacts biogeochemical cycles in the ocean. Culture‐based work has illustrated the diversity of diatom–prokaryote interactions, but the question of whether these associations can affect the spatial distribution of microbial communities is open. Here, we investigated the relationship between assemblages of diatoms and of heterotrophic prokaryotes in surface waters of the Indian sector of the Southern Ocean in early spring. The community composition of diatoms and that of total and active prokaryotes were different among the major ocean zones investigated. We found significant relationships between compositional changes of diatoms and of prokaryotes. In contrast, spatial changes in the prokaryotic community composition were not related to geographic distance and to environmental parameters when the effect of diatoms was accounted for. Diatoms explained 30% of the variance in both the total and the active prokaryotic community composition in early spring in the Southern Ocean. Using co‐occurrence analyses, we identified a large number of highly significant correlations between abundant diatom species and prokaryotic taxa. Our results show that key diatom species of the Southern Ocean are each associated with a distinct prokaryotic community, suggesting that diatom assemblages contribute to shaping the habitat type for heterotrophic prokaryotes.