bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association meta-analysis of cocaine dependence: Shared genetics with comorbid conditions
Authors: Cabana-Domínguez Judit , Shivalikanjli Anu , Fernàndez-Castillo Noèlia , Cormand Bru
Published: July 2018

Cocaine dependence is a complex psychiatric disorder that is highly comorbid with other psychiatric traits. Twin and adoption studies suggest that genetic variants contribute substantially to cocaine dependence susceptibility, which has an estimated heritability of 65-79%. Here we performed a meta-analysis of genome-wide association studies of cocaine dependence using four datasets from the dbGaP repository (2,085 cases and 4,293 controls, all of them selected by their European ancestry). Although no genome-wide significant hits were found in the SNP-based analysis, the gene-based analysis identified HIST1H2BD as associated with cocaine-dependence (10% FDR). This gene is located in a region on chromosome 6 enriched in histone-related genes, previously associated with schizophrenia (SCZ). Furthermore, we performed LD Score regression analysis with comorbid conditions and found significant genetic correlations between cocaine dependence and SCZ, ADHD, major depressive disorder (MDD) and risk taking. We also found, through polygenic risk score analysis, that all tested phenotypes can significantly predict cocaine dependence status: SCZ (R2=2.28%; P=1.21e-26), ADHD (R2=1.39%; P=4.5e-17), risk taking (R2=0.60%; P=2.7e-08), MDD (R2=1.21%; P=4.35e-15), children’s aggressiveness (R2=0.3%; P=8.8e-05) and antisocial behavior (R2=1.33%; P=2.2e-16). To our knowledge, this is the largest reported cocaine dependence GWAS meta-analysis in European-ancestry individuals. We identified suggestive associations in regions that may be related to cocaine dependence and found evidence for shared genetic risk factors between cocaine dependence and several comorbid psychiatric traits. However, the sample size is limited and further studies are needed to confirm these results.
How many individuals share a mitochondrial genome?
Authors: Andersen Mikkel M , Balding David J
Published: July 2018

Mitochondrial DNA (mtDNA) is useful to assist with identification of the source of a biological sample, or to confirm matrilineal relatedness. Although the autosomal genome is much larger, mtDNA has an advantage for forensic applications of multiple copy number per cell, allowing better recovery of sequence information from degraded samples. In addition, biological samples such as fingernails, old bones, teeth and hair have mtDNA but little or no autosomal DNA. The relatively low mutation rate of the mitochondrial genome (mitogenome) means that there can be large sets of matrilineal-related individuals sharing a common mitogenome. Here we present the mitolina simulation software that we use to describe the distribution of the number of mitogenomes in a population that match a given mitogenome, and investigate its dependence on population size and growth rate, and on a database count of the mitogenome. Further, we report on the distribution of the number of meioses separating pairs of individuals with matching mitogenome. Our results have important implications for assessing the weight of mtDNA profile evidence in forensic science, but mtDNA analysis has many non-human applications, for example in tracking the source of ivory. Our methods and software can also be used for simulations to validate models of population history in human or non-human populations.

Author Summary

The maternally-inherited mitochondrial DNA (mtDNA) represents only a small fraction of the human genome, but mtDNA profiles are important in forensic science, for example when a biological evidence sample is degraded or when maternal relatedness is questioned. For forensic mtDNA analysis, it is important to know how many individuals share a mtDNA profile. We present a simulation model of mtDNA profile evolution, implemented in open-source software, and use it to describe the distribution of the number of individuals with matching mitogenomes, and their matrilineal relatedness. The latter is measured as the number of mother-child pairs in the lineage linking two matching individuals. We also describe how these distributions change when conditioning on a count of the profile in a frequency database.
Individual differences in cortical processing speed predict cognitive abilities: a model-based cognitive neuroscience account
Authors: Schubert Anna-Lena , Nunez Michael D. , Hagemann Dirk , Vandekerckhove Joachim
Published: July 2018

Previous research has shown that individuals with greater cognitive abilities display a greater speed of higher-order cognitive processing. These results suggest that speeded neural information-processing may facilitate evidence accumulation during decision making and memory updating and thus yield advantages in general cognitive abilities. We used a hierarchical Bayesian cognitive modeling approach to test the hypothesis that individual differences in the velocity of evidence accumulation mediate the relationship between neural processing speed and cognitive abilities. We found that a higher neural speed predicted both the velocity of evidence accumulation across behavioral tasks as well as cognitive ability test scores. However, only a small part of the association between neural processing speed and cognitive abilities was mediated by individual differences in the velocity of evidence accumulation. The model demonstrated impressive forecasting abilities by predicting 36% of individual variation in cognitive ability test scores in an entirely new sample solely based on their electrophysiological and behavioral data. Our results suggest that individual differences in neural processing speed might affect a plethora of higher-order cognitive processes, that only in concert explain the large association between neural processing speed and cognitive abilities, instead of the effect being entirely explained by differences in evidence accumulation speeds.
Local adaptation under gene flow: Recombination, conditional neutrality and genetic trade-offs shape genomic patterns inArabidopsis lyrata
Authors: Hämälä Tuomas , Savolainen Outi
Published: July 2018

Short-scale local adaptation is a complex process involving selection, migration and drift. The expected effects on the genome are well grounded in theory, but examining these on an empirical level has proven difficult, as it requires information about local selection, demographic history and recombination rate variation. Here, we use locally adapted and phenotypically differentiatedArabidopsis lyratapopulations from two altitudinal gradients in Norway to test these expectations at the whole-genome level. Demography modelling indicates that populations within the gradients diverged less than 2000 years ago and that the sites are connected by gene flow. The gene flow estimates are, however, highly asymmetric with migration from high to low altitudes being several times more frequent thanvice versa. To detect signatures of selection for local adaptation, we estimate patterns of lineage specific differentiation among these populations. Theory predicts that gene flow leads to concentration of adaptive loci in areas of low recombination; a pattern we observe in both lowland-alpine comparisons. Although most selected loci display patterns of conditional neutrality, we found indications of genetic trade-offs, with one locus particularly showing high divergence and signs of selection in both populations. Our results further suggest that resistance to solar radiation is an important adaptation to alpine environments, while vegetative growth and bacterial defense are indicated as selected traits in the lowland habitats. These results provide insights into genetic architectures and evolutionary processes driving local adaptation under gene flow. We also contribute to understanding of traits and biological processes underlying alpine adaptation in northern latitudes.
Genome-wide Marginal Epistatic Association Mapping in Case-Control Studies
Authors: Crawford Lorin , Zhou Xiang
Published: July 2018

Epistasis, commonly defined as the interaction between genetic loci, is an important contributor to the genetic architecture underlying many complex traits and common diseases. Most existing epistatic mapping methods in genome-wide association studies explicitly search over all pairwise or higher-order interactions. However, due to the potentially large search space and the resulting multiple testing burden, these conventional approaches often suffer from heavy computational cost and low statistical power. A recently proposed attractive alternative for mapping epistasis focuses instead on detecting marginal epistasis, which is defined as the combined pairwise interaction effects between a given variant and all other variants. By searching for marginal epistatic effects, one can identify genetic variants that are involved in epistasis without the need to identify the exact partners with which the variants interact — thus, potentially alleviating much of the statistical and computational burden associated with conventional epistatic mapping procedures. However, previous marginal epistatic mapping methods are based on quantitative trait models. As we will show here, these lack statistical power in case-control studies. Here, we develop a liability threshold mixed model that extends marginal epistatic mapping to case-control studies. Our method properly accounts for case-control ascertainment and the binary nature of case-control data. We refer to this method as the liability threshold marginal epistasis test (LT-MAPIT). With simulations, we illustrate the benefits of LT-MAPIT in terms of providing effective type I error control, and being more powerful than both existing marginal epistatic mapping methods and conventional explicit search-based approaches in case-control data. We finally apply LT-MAPIT to identify both marginal and pairwise epistasis in seven complex diseases from the Wellcome Trust Case Control Consortium (WTCCC) 1 study.
Tumor extracellular vesicles are required for tumor-associated macrophage programming
Authors: Rabe Daniel C , Rustandy Felicia D , Lee Jiyoung , Rosner Marsha Rich
Published: July 2018

Triple-negative breast cancers (TNBC) are highly infiltrated by tumor-associated macrophages (TAMs) that promote tumor growth, survival, metastasis and therapeutic resistance. Although cytokines such as CCL5 have been implicated in TAM recruitment to TNBC tumors, the mechanism by which tumor cells educate TAMs is not understood. Here we show that tumor EVs are both necessary and sufficient for programming TAMs toward a pro-metastatic phenotype. The mechanism involves CCL5 regulation of tumor extracellular vesicles (EVs), which activate TLR2 and TLR3, leading to secretion of a common set of cytokines that further stimulate tumor cell invasion and metastasis as well as alter the tumor microenvironment. Cytokine expression is significantly correlated to CCL5 expression and up-regulated in TNBC patient tumors. These results demonstrate for the first time that tumor EVs are key mediators of TAM education, phenocopy the pro-metastatic and drug resistant state of the tumors to TAMs, and illustrate the potential clinical relevance of these findings to TNBC patients.

Highlights

Tumor extracellular vesicles (EVs) are required for pro-metastatic programming of tumor-associated macrophages (TAMs)

Tumor CCL5 and macrophage TLR signaling mediate tumor EV programming of TAMs in TNBCs

Tumor EVs mediate drug resistance in TAMs and alter recruitment of regulatory T-cells.

Cytokines expressed by EV-educated TAMs are enriched and correlate with CCL5 in human TNBC patients.

eTOC

Chemokines such as CCL5 recruit tumor-associated macrophages (TAMs) that are required for metastasis, but TAM programming is not understood. Rabe et al. show that tumor extracellular vesicles (EVs) are required for programming TAMs via Toll-like Receptors (TLRs) to phenocopy the tumor, rewire the microenvironment, drive metastasis and promote immune cell evasion.
Transient DNA Binding Induces RNA Polymerase II Compartmentalization During Herpesviral Infection Distinct From Phase Separation
Authors: McSwiggen David T , Hansen Anders S , Marie-Nelly Hervé , Teves Sheila , Heckert Alec B , Dugast-Darzacq Claire , Hao Yvonne , Umemoto Kayla K , Tjian Robert , Darzacq Xavier
Published: July 2018

During lytic infection, Herpes Simplex Virus 1 generates replication compartments (RCs) in host nuclei that efficiently recruit protein factors, including host RNA Polymerase II (Pol II). Pol II and other cellular factors form hubs in uninfected cells that are proposed to phase separate via multivalent protein-protein interactions mediated by their intrinsically disordered regions. Using a battery of live cell microscopic techniques, we show that although RCs superficially exhibit many characteristics of phase separation, the recruitment of Pol II instead derives from nonspecific interactions with the viral DNA. We find that the viral genome remains nucleosome-free, profoundly affecting the way Pol II explores RCs by causing it to repetitively visit nearby binding sites, thereby creating local Pol II accumulations. This mechanism, distinct from phase separation, allows viral DNA to outcompete host DNA for cellular proteins. Our work provides new insights into the strategies used to create local molecular hubs in cells.
Species Designations Belie Phenotypic and Genotypic Heterogeneity in Oral Streptococci
Authors: Velsko Irina M. , Chakraborty Brinta , Nascimento Marcelle M. , Burne Robert A. , Richards Vincent P.
Published: July 2018

Health-associated oralStreptococcusspecies are promising probiotic candidates to protect against dental caries. Ammonia production through the arginine deiminase system (ADS), which can increase the pH of oral biofilms, and direct antagonism of caries-associated bacterial species are desirable properties for oral probiotic strains. ADS and antagonistic activities can vary dramatically among individuals, but the genetic basis for these differences is unknown. We sequenced whole genomes of a diverse set of clinical oralStreptococcusisolates and examined the genetic basis of variability in ADS and antagonistic activities. A total of 113 isolates were included and represented ten species:S. australis, A12-like,S. cristatus,S. gordonii,S. intermedius,S. mitis,S. oralisincludingS. oralissubsp.dentisani,S. parasanguinis, S. salivarius, andS. sanguinis. Mean ADS activity and antagonism onStreptococcus mutansUA159 were measured for each isolate, and each isolate was whole genome-shotgun sequenced on an Illumina MiSeq. Phylogenies were built of genes known to be involved in ADS activity and antagonism. Several approaches to correlate the pan-genome with phenotypes were performed. Phylogenies of genes previously identified in ADS activity and antagonism grouped isolates by species but not by phenotype. GWAS identified additional genes potentially involved in ADS activity or antagonism across all the isolates we sequenced as well as within several species. Phenotypic heterogeneity in oral streptococci is not necessarily reflected by genotype and is not species-specific. Probiotic strains must be carefully selected based on characterization of each strain, and not based on inclusion within a certain species.

Importance

Representative type strains are commonly used to characterize bacterial species, yet species are phenotypically and genotypically heterogeneous. Conclusions about strain physiology and activity based on a single strain therefore may be inappropriate and misleading. When selecting strains for probiotic use, the assumption that all strains within a species share the same desired probiotic characteristics share those characteristics may result in selection of a strain that lacks the desired traits, and therefore makes a minimally effective or ineffective probiotic. Health-associated oral streptococci are promising candidates for anti-caries probiotics, but strains need to be carefully selected based on observed phenotypes. We characterized the genotype and anti-caries phenotypes of strains from ten species of oral Streptococci and demonstrate poor correlation between genotype and phenotype across all species.
Survival of the frequent at finite population size and mutation rate: bridging the gap between quasispecies and monomorphic regimes with a simple model
Authors: Khatri Bhavin S.
Published: July 2018

In recent years, there has been increased attention on the non-trivial role that genotype-phenotype maps play in the course of evolution, where natural selection acts on phenotypes, but variation arises at the level of mutations. Understanding such mappings is arguably the next missing piece in a fully predictive theory of evolution. Although there are theoretical descriptions of such mappings for the monomorphic (Nμ ≪ 1) and deterministic or very strong mutation (Nμ ⋙ 1) limit, given by developments of Iwasa’s free fitness and quasispecies theories, respectively, there is no general description for the intermediate regime where Nμ ~ 1. In this paper, we address this by transforming Wright’s well-known stationary distribution of genotypes under selection and mutation to give the probability distribution of phenotypes, assuming a general genotype-phenotype map. The resultant distribution shows that the degeneracies of each phenotype appear by weighting the mutation term; this gives rise to a bias towards phenotypes of larger degeneracy analogous to quasispecies theory, but at finite population size. On the other hand we show that as population size is decreased, again phenotypes of higher degeneracy are favoured, which is a finite mutation description of the effect of sequence entropy in the monomorphic limit. We also for the first time (to the author’s knowledge) provide an explicit derivation of Wright’s stationary distribution of the frequencies of multiple alleles.
Detecting T-cell receptors involved in immune responses from single repertoire snapshots
Authors: Pogorelyy Mikhail V. , Minervina Anastasia A. , Shugay Mikhail , Chudakov Dmitriy M. , Lebedev Yuri B. , Mora Thierry , Walczak Aleksandra M.
Published: July 2018

Hypervariable T-cell receptors (TCR) play a key role in adaptive immunity, recognising a vast diversity of pathogen-derived antigens. High throughput sequencing of TCR repertoires (RepSeq) produces huge datasets of T-cell receptor sequences from blood and tissue samples [1, 2]. However, our ability to extract clinically relevant information from RepSeq data is limited, mainly because little is known about TCR-disease associations. Here we present a statistical approach called ALICE (Antigen-specific Lymphocyte Identification by Clustering of Expanded sequences) that identifies TCR sequences that are actively involved in the current immune response from a single RepSeq sample, and apply it to repertoires of patients with a variety of disorders — autoimmune disease (ankylosing spondylitis [3]), patients under cancer immunotherapy [4, 5], or subject to an acute infection (live yellow fever vaccine [6]). The methods robustness is demonstrated by the agreement of its predictions with independent assays, and is supported by its ability to selectively detect responding TCR in the memory but not in the naïve subset. ALICE requires no longitudinal data collection [6, 7] nor large cohorts [8–10], and is thus directly applicable to most RepSeq datasets. Its results facilitate the identification of TCR variants associated with a wide variety of diseases and conditions, which can be used for diagnostics, rational vaccine design and evaluation of the adaptive immune system state.
Nearly uniform sampling of crystal orientations
Authors: Quey Romain , Villani Aurélien , Maurice Claire
Published: July 2018

A method is presented for generating nearly uniform distributions of three-dimensional orientations in the presence of symmetry. The method is based on the Thomson problem, which consists in finding the configuration of minimal energy of N electrons located on a unit sphere – a configuration of high spatial uniformity. Orientations are represented as unit quaternions, which lie on a unit hypersphere in four-dimensional space. Expressions of the electrostatic potential energy and Coulomb's forces are derived by working in the tangent space of orientation space. Using the forces, orientations are evolved in a conventional gradient-descent optimization until equilibrium. The method is highly versatile as it can generate uniform distributions for any number of orientations and any symmetry, and even allows one to prescribe some orientations. For large numbers of orientations, the forces can be computed using only the close neighbourhoods of orientations. Even uniform distributions of as many as 106 orientations, such as those required for dictionary-based indexing of diffraction patterns, can be generated in reasonable computation times. The presented algorithms are implemented and distributed in the free (open-source) software package Neper.
A framework for intelligent Twitter data analysis with non-negative matrix factorization
Authors: Casalino Gabriella , Castiello Ciro , Del Buono Nicoletta , Mencar Corrado
Published: July 2018

Purpose

The purpose of this paper is to propose a framework for intelligent analysis of Twitter data. The purpose of the framework is to allow users to explore a collection of tweets by extracting topics with semantic relevance. In this way, it is possible to detect groups of tweets related to new technologies, events and other topics that are automatically discovered.

Design/methodology/approach

The framework is based on a three-stage process. The first stage is devoted to dataset creation by transforming a collection of tweets in a dataset according to the vector space model. The second stage, which is the core of the framework, is centered on the use of non-negative matrix factorizations (NMF) for extracting human-interpretable topics from tweets that are eventually clustered. The number of topics can be user-defined or can be discovered automatically by applying subtractive clustering as a preliminary step before factorization. Cluster analysis and word-cloud visualization are used in the last stage to enable intelligent data analysis.

Findings

The authors applied the framework to a case study of three collections of Italian tweets both with manual and automatic selection of the number of topics. Given the high sparsity of Twitter data, the authors also investigated the influence of different initializations mechanisms for NMF on the factorization results. Numerical comparisons confirm that NMF could be used for clustering as it is comparable to classical clustering techniques such as spherical k-means. Visual inspection of the word-clouds allowed a qualitative assessment of the results that confirmed the expected outcomes.

Originality/value

The proposed framework enables a collaborative approach between users and computers for an intelligent analysis of Twitter data. Users are faced with interpretable descriptions of tweet clusters, which can be interactively refined with few adjustable parameters. The resulting clusters can be used for intelligent selection of tweets, as well as for further analytics concerning the impact of products, events, etc. in the social network.
Parameters of automated fraud detection techniques during online transactions
Authors: Khattri Vipin , Singh Deepak Kumar
Published: July 2018

Purpose

This paper aims to provide information of parameters and techniques used in the automated fraud detection system during online transaction. With the increase in the use of online transactions, the concerns regarding data security have also increased. To tackle the frauds, lot of research has been done and plethora of papers are available on the related topics. The purpose of this paper is to provide the clear pathway for researchers to move in the direction of development of automated fraud detection system to prevent the fraud during online transaction.

Design/methodology/approach

This literature review analyses and compares the different types of techniques for detecting fraud during online transaction. An in-depth study of the most prominent journals has been done and the core methodology of the papers has been presented. This article also shed some light on different types of parameters used in fraud detection techniques during online transaction.

Findings

There are vast varieties of various fraud detection techniques, and every technique has completed task in its own way. After studying approximately 41 research papers, 14 books and four reports, in total 30 parameters have been identified and a detailed study of the parameters has been presented. The parameters are also listed with their details that how these parameters are used in the security system for detecting online transaction fraud.

Research limitations/implications

This paper provides empirical insight about the parameters and their prominence in the development of automated fraud detection security system of online transaction. This paper encourages the researchers to development of improved fraud detection system.

Practical implications

This paper will pave the way for researchers to do a focused research on the fraud detection methodologies. The analysis will help in zeroing down the most prevalent topic of research in this field. The researchers will be able to understand the internal details of parameters and techniques used in the fraud detection systems. This literature also helps the research to think in a variety of ways that how these parameters will be used in the development of fraud detection system.

Originality/value

This paper is one of the most comprehensive reviews in its field. It tries and attempts to fill a void created because of lack of compilation of the laid fraud detection parameters.
The battle against fraud: do reporting mechanisms work?
Authors: Peltier-Rivest Dominic
Published: July 2018

Purpose

This paper aims to explore how well reporting mechanisms work, investigate current trends and develop a framework for implementing effective mechanisms.

Design/methodology/approach

This study is based on primary and secondary data, criminology theory and best corporate strategies.

Findings

This study shows that the median number of annual reports equals 1.2 per cent of the number of employees in an organization and that 40 per cent of these reports have merit (Navex Global, 2014). In addition, 42.2 per cent of all frauds are detected through internal reports, whatever their form. Organizations with formal reporting mechanisms sustain fraud losses that are 40.5 per cent less than other organizations (ACFE, 2014). Moreover, employees are more willing to report theft, human resource and workplace issues than fraud and corruption, while 21 per cent of all whistleblowers have experienced some form of retaliation for reporting wrongdoing (Ethics Resource Center, 2014). Results from primary data show that the option to remain anonymous is offered only by 74 per cent of all reporting mechanisms. This paper argues that effective reporting mechanisms should actively encourage whistleblowing, that all credible allegations should be independently investigated and that whistleblowers should be offered the option to remain anonymous. The oversight and the daily administration of reporting mechanisms should be given to two different parties who are independent from management and who do not participate in incentive compensation plans (Lipman, 2012).

Research limitations/implications

This paper extends previous research by reporting on current hotline trends and integrating various factors into a framework to implement effective reporting mechanisms.

Originality/value

It is the first paper to investigate the effectiveness of reporting mechanisms and current policy trends.
Understanding fraud in Malaysian SMEs
Authors: N’Guilla Sow Abdoulaye , Basiruddin Rohaida , Abdul Rasid Siti Zaleha , Husin Maizaitulaidawati Md
Published: July 2018

Purpose

The paper aims to provide an overview of fraud risk among Malaysian small- and medium-sized enterprises (SMEs). In particular, the authors investigate the understanding of SME owners and managers on fraud schemes and the usage of antifraud measures.

Design/methodology/approach

A sample of 126 Malaysian SMEs from different industries participated in this study.

Findings

The results suggest that Malaysian SMEs are exposed to a broad range of fraud schemes, yet few take actions to prevent these frauds.

Practical implications

The findings should be useful to academic researchers, entrepreneurs, regulators and others who are interested in understanding the fraud risk in small businesses.

Originality/value

This study extends and contributes to prior literature by linking the state of fraud and SMEs in developing countries.
Social influences on survival and reproduction: Insights from a long‐term study of wild baboons
Authors: Alberts Susan C.
Published: July 2018

For social species, the environment has two components: physical and social. The social environment modifies the individual's interaction with the physical environment, and the physical environment may in turn impact individuals’ social relationships. This interplay can generate considerable variation among individuals in survival and reproduction. Here, I synthesize more than four decades of research on the baboons of the Amboseli basin in southern Kenya to illustrate how social and physical environments interact to affect reproduction and survival.

For immature baboons, social behaviour can both mitigate and exacerbate the challenge of survival. Only c. 50% of live‐born females and c. 44% of live‐born males reach the median age of first reproduction. Variation in pre‐adult survival, growth and development is associated with multiple aspects of the social environment. For instance, conspecifics provide direct care and are a major source of social knowledge about food and the environment, but conspecifics can also represent a direct threat to survival through infanticide.

In adulthood, both competition (within and between social groups) and cooperative affiliation (i.e. collective action and/or the exchange of social resources such as grooming) are prominent features of baboon social life and have important consequences for reproduction and survival. For instance, adult females with higher social dominance ranks have accelerated reproduction, and adult females that engage in more frequent affiliative social interactions have higher survival throughout adulthood.

The early life environment also has important consequences for adult reproduction and survival, as in a number of other bird and mammal species. In seasonal breeders, early life effects often apply to entire cohorts; in contrast, in nonseasonal and highly social species such as baboons, early life effects are more individual‐specific, stemming from considerable variation not only in the early physical environment (even if they are born in the same year) but also in the particulars of their social environment.
Variation in reproductive modes and population genetic structures of a monocarpic perennial herb, Cardiocrinum cordatum, in relation to habitat fragmentation
Authors: Narumi Tadashi , Ohara Masashi
Published: July 2018

Reproductive systems are recognized as having a profound influence on the extent and structure of genetic variation in plant populations. To investigate the spatiotemporal variation in the reproductive modes (sexual and vegetative reproduction) and population genetic structures of a monocarpic perennial herb, Cardiocrinum cordatum (liliaceae), we selected a variety of habitats (e.g. large forested area including primeval forest, small fragmented secondary forest, and so on) around Sapporo City, Japan. We conducted breeding experiments, monitored the fate and growth of marked individuals for 3 years, and also analyzed the spatiotemporal genetic variation of flowering plants within the populations using allozyme variation. Plants emasculated prior to anthesis produced mature fruits in all populations examined. However, seed production was significantly lower in the small fragmented populations, possibly because of the low availability of pollinators and subsequent pollen limitation. In these fragmented populations, the mature flowering plants tended to be more dependent on vegetative reproduction for their recruitment, because they can only produce flowers once in their lifetime. Genetic diversity using samples from mature flowering plants in each population was lower in the small fragmented populations than in the large populations. In addition, although genotypic compositions in the fragmented populations were more or less similar during the 3 years of the study, the dominant genotypes changed temporally and spatially every year in the large populations. The present study demonstrated that the reproductive features of C. cordatum can be altered in various environmental conditions, such as habitat fragmentation, and these changes considerably affected the population genetic structures and vice versa.
Ten‐year trends in the price differential between healthier and less healthy foods in New Zealand
Authors: Mackay Sally , Vandevijvere Stefanie , Lee Arier
Published: July 2018

Aim

To measure the relative change in price of healthier and less healthy foods over 10 years in New Zealand.

Methods

Foods in the New Zealand food price index were classified as healthy and less healthy (WHO Europe Nutrient Profile Model) and by degree of processing (according to the NOVA classification). The change in price from February 2007 to January 2017 was analysed using a mixed model for repeated measures with healthiness (or level of processing), season and time added as covariates.

Results

Eighty‐eight (of 155) relevant items had sufficient information on weight and healthiness. The trend of increasing food prices over time was similar for healthier and less healthy foods and between the three categories of processing. There was a statistically significant interaction (P = 0.014) between seasons and healthiness of foods, and seasons and degrees of processing (P < 0.001). The price of healthy foods and minimally processed foods fluctuated more by season compared to less healthy foods and processed foods.

Conclusions

Food prices increased over time with no significant difference in the rate of change for healthier and less healthy foods, and between foods of different degrees of processing. This method can be used to routinely monitor relative changes in food prices according to healthiness.
Seasonal changes in fish catch and environmental variables in a large Tropical Lake, Volta, Ghana
Authors: Mensah Emmanuel T‐D. , Dankwa Hederick R. , Lauridsen Torben L. , Asmah Ruby , Campion Benjamin B. , Edziyie Regina
Published: July 2018

Fish species assemblage and selected environmental variables were monitored in Lake Volta from September 2014 to August 2016 to determine seasonal variability in species composition, catch and environmental variables that determine the structure of the fish community. A total of 1,557 individual fish belonging to 41 species, 25 genera and 13 families were recorded. The important fish species with respect to frequency of occurrence, abundance and weight, respectively, were as follows: Chrysichthys (100%; 43.03%; 17.93%), tilapias (100%; 28.97%; 17.86%), Alestes (100%; 14.13%; 32.10%) and Bagrus (91.67%; 5.65%; 12.80%) in that order. The composition of fish species and their temporal variation in experimental catches were similar to that of commercial catches. There were no significant differences (p > 0.05) in species abundance, weight and diversity indices between the dry and wet seasons. The modal class of length frequency distribution of the dominant species in the catch, Chrysichthys, reduced from 125 mm in 2006 to 95 mm in the current study indicating overfishing. Environmental variables considered showed little variation and within optimal ranges for fish survival and did not differ significantly between seasons. Canonical Correspondence Analysis showed that environmental variables explained 43.30% of the variation in species abundance with Lake water level, nitrite‐nitrogen and total dissolved solids being the main environmental factors influencing the structure of the fish community.
Reproductive investments of a small, arid zone tortoise Chersobius signatus: Follicle and egg development
Authors: Hofmeyr Margaretha D. , Henen Brian T. , Loehr Victor J. T.
Published: July 2018

We used ultrasonography and radiography to evaluate whether body size (BS), body condition (BC) and environmental factors influenced reproductive investments by Chersobius signatus in September 2000 and from September 2003 to November 2004. Follicle volume increased with increasing BS, BC and rainfall but decreased with increasing temperature. Egg volume averaged 8.8% of body volume, increased allometrically with BS, but was not affected by BC, rainfall or temperature and did not differ between first and second clutches. Most females produced at least one single‐egg clutch per year, even when BC was low. Many females produced two, possibly more, clutches but some forfeited reproduction in some years. Females often retained large follicles from one season to the next with 18%–71% carrying pre‐ovulatory sized follicles in different times of the year. Increasing temperatures likely influenced timing of first ovulations in August while decreasing water and food availability, linked with high temperatures, possibly terminated ovulations by November. The gravid season was short compared to other winter‐rainfall tortoises in South Africa. We propose that the females' small bodies may constrain investments in eggs, resulting in low fecundity, which is countered by producing large hatchlings with high survivorship in an arid habitat.
Target site pharmacokinetics of doxycycline for rosacea in healthy volunteers is independent of the food effect
Authors: Pal Arindam , Matzneller Peter , Gautam Anirudh , Österreicher Zoe , Wulkersdorfer Beatrix , Reiter Birgit , Stimpfl Thomas , Zeitlinger Markus
Published: July 2018

Aims

Doxycycline (DFD‐09) oral capsules 40 mg are approved for the treatment of inflammatory lesions of rosacea. Unlike the food‐induced lowering of doxycycline's peak plasma concentration (Cmax), its exposure under fed conditions in the skin, the drug's target site for rosacea, is unknown. The present study explored the effect of food on the dermal pharmacokinetics of doxycycline.

Methods

The pharmacokinetics of doxycycline in the dermal interstitial fluid (d‐ISF) and plasma of healthy volunteers were assessed in parallel groups under fed (n = 6) and fasting (n = 6) conditions during a 14‐day once‐daily treatment course with doxycycline oral capsules 40 mg (DFD‐09). Sampling of d‐ISF and plasma was performed on days 1, 10 (fasting group d‐ISF only) and 14.

Results

Twelve subjects were randomized, and 11 analysed. No causally drug‐related adverse events occurred. Dermal doxycycline exposures (Cmax and area under the curve) under the fed state were about 30% lower than under the fasting state at day 1 but were similar at steady state. In analogy to skin, plasma exposure showed no between‐group difference at steady state. Accumulation ratios were higher in the skin than in plasma. Correcting for plasma protein binding (~90%), dermal doxycycline exposure was approximately threefold higher than unbound plasma exposure.

Conclusions

At steady state, doxycycline concentrations in the skin of fed and fasting healthy volunteers were comparable. Doxycycline's efficacy in rosacea is possibly due to considerable dermal accumulation of unbound doxycycline and is independent of the effect of food.
Small rock‐slope failures conditioned by Holocene permafrost degradation: a new approach and conceptual model based on Schmidt‐hammer exposure‐age dating, Jotunheimen, southern Norway
Authors: Matthews John A. , Winkler Stefan , Wilson Peter , Tomkins Matt D. , Dortch Jason M. , Mourne Richard W. , Hill Jennifer L. , Owen Geraint , Vater Amber E.
Published: July 2018

Rock‐slope failures (RSFs) constitute significant natural hazards, but the geophysical processes that control their timing are poorly understood. However, robust chronologies can provide valuable information on the environmental controls on RSF occurrence: information that can inform models of RSF activity in response to climatic forcing. This study uses Schmidt‐hammer exposure‐age dating (SHD) of boulder deposits to construct a detailed regional Holocene chronology of the frequency and magnitude of small rock‐slope failures (SRSFs) in Jotunheimen, Norway. By focusing on the depositional fans of SRSFs (≤103 m3), rather than on the corresponding features of massive RSFs (~108 m3), 92 single‐event RSFs are targeted for chronology building. A weighted SHD age–frequency distribution and probability density function analysis indicated four centennial‐ to millennial‐scale periods of enhanced SRSF frequency, with a dominant mode at ~4.5 ka. Using change detection and discreet Meyer wavelet analysis, in combination with existing permafrost depth models, we propose that enhanced SRSF activity was primarily controlled by permafrost degradation. Long‐term relative change in permafrost depth provides a compelling explanation for the high‐magnitude departures from the SRSF background rate and accounts for: (i) the timing of peak SRSF frequency; (ii) the significant lag (~2.2 ka) between the Holocene Thermal Maximum and the SRSF frequency peak; and (iii) the marked decline in frequency in the late‐Holocene. This interpretation is supported by geomorphological evidence, as the spatial distribution of SRSFs is strongly correlated with the aspect‐dependent lower altitudinal limit of mountain permafrost in cliff faces. Results are indicative of a causal relationship between episodes of relatively warm climate, permafrost degradation and the transition to a seasonal‐freezing climatic regime. This study highlights permafrost degradation as a conditioning factor for cliff collapse, and hence the importance of paraperiglacial processes; a result with implications for slope instability in glacial and periglacial environments under global warming scenarios.
VCE‐004.3, a cannabidiol aminoquinone derivative, prevents bleomycin‐induced skin fibrosis and inflammation through PPARγ‐ and CB2 receptor‐dependent pathways
Authors: del Rio Carmen , Cantarero Irene , Palomares Belén , Gómez‐Cañas María , Fernández‐Ruiz Javier , Pavicic Carolina , García‐Martín Adela , Luz Bellido Maria , Ortega‐Castro Rafaela , Pérez‐Sánchez Carlos , López‐Pedrera Chary , Appendino Giovanni , Calzado Marco A , Muñoz Eduardo
Published: July 2018

Background and Purpose

The endocannabinoid system and PPARγ are important targets for the development of novel compounds against fibrotic diseases such as systemic sclerosis (SSc), also called scleroderma. The aim of this study was to characterize VCE‐004.3, a novel cannabidiol derivative, and study its anti‐inflammatory and anti‐fibrotic activities.

Experimental Approach

The binding of VCE‐004.3 to CB1 and CB2 receptors and PPARγ and its effect on their functional activities were studied in vitro and in silico. Anti‐fibrotic effects of VCE‐004.3 were investigated in NIH‐3T3 fibroblasts and human dermal fibroblasts. To assess its anti‐inflammatory and anti‐fibrotic efficacy in vivo, we used two complementary models of bleomycin‐induced fibrosis. Its effect on ERK1/2 phosphorylation induced by IgG from SSc patients and PDGF was also investigated.

Key Results

VCE‐004.3 bound to and activated PPARγ and CB2 receptors and antagonized CB1 receptors. VCE‐004.3 bound to an alternative site at the PPARγ ligand binding pocket. VCE‐004.3 inhibited collagen gene transcription and synthesis and prevented TGFβ‐induced fibroblast migration and differentiation to myofibroblasts. It prevented skin fibrosis, myofibroblast differentiation and ERK1/2 phosphorylation in bleomycin‐induced skin fibrosis. Furthermore, it reduced mast cell degranulation, macrophage activation, T‐lymphocyte infiltration, and the expression of inflammatory and profibrotic factors. Topical application of VCE‐004.3 also alleviated skin fibrosis. Finally, VCE‐004.3 inhibited PDGF‐BB‐ and SSc IgG‐induced ERK1/2 activation in fibroblasts.

Conclusions and Implications

VCE‐004.3 is a novel semisynthetic cannabidiol derivative that behaves as a dual PPARγ/CB2 agonist and CB1 receptor modulator that could be considered for the development of novel therapies against different forms of scleroderma.
Developing a database for Rett syndrome research performed in the European Union: A resource for researchers and stakeholders
Authors: Akinsolu Folahanmi Tomiwa , Balczár Eszter , Kovács Nóra , Gáll Tibor , Harangi Mariann , Varga Orsolya
Published: July 2018

Background

For most rare diseases, which are often significantly under‐resourced, sufficient information on funding landscape is missing, which may prevent effective use of research resources and be an obstacle to making effective decisions on research. The objective of this research was to create a database of Rett syndrome research projects carried out in the European Union (EU) and to provide a research landscape analysis.

Method

Websites of organizations funding research projects were identified and systematically checked. Projects were analysed by date, place, funder types, and research topics.

Results

The analysis revealed that the total expenditure on Rett syndrome research was almost €70 million, allocated among 247 projects mostly performed in Italy and the United Kingdom. The main research sponsor was the European Commission.

Highlighting research trends and gaps, this work facilitates changes in rare disease research data management.

Conclusion

This work demonstrates the feasibility of creating an EU‐based research database on Rett syndrome projects. It provides a source of information on research development which is useful for individuals, organizations and key players in the private and public sector to make progressive decisions on Rett syndrome research.
Quantifying current and potential contributions of Australian indigenous peoples to threatened species management
Authors: Leiper Ian , Zander Kerstin K. , Robinson Cathy J. , Carwadine Josie , Moggridge Bradley J. , Garnett Stephen T.
Published: July 2018

Formal engagement of indigenous peoples in conservation is increasing globally and leads to multiple benefits to communities while contributing to national and international biodiversity goals and obligations. This and ongoing declines in biodiversity have led to calls to increase opportunities for indigenous people to engage in managing their estates. However, there is no overarching understanding of indigenous peoples’ involvement in conservation, which limits the identification of new opportunities. We amalgamated information across governments and large nongovernmental organizations in the megadiverse country of Australia to quantify the involvement of indigenous people in management of threatened species. We identified 153 Australian‐based projects undertaken by different indigenous groups around the nation in 2015 and 2016 that included explicit funds for management of threatened species or threatened ecosystems. Most were in remote parts of western and northern Australia. Almost one‐quarter of all threatened animals and 2% of threatened plants were the subject of some formal conservation action by indigenous people. Occurrence records for 1574 threatened species showed that 823 (89.2%) of 923 species recorded on indigenous peoples’ lands were not listed in management projects. This gap may represent new opportunities for conservation initiatives. Because at least 59.5% of Australia's threatened species occur on indigenous peoples’ lands, efforts to build appropriate and effective indigenous conservation alliances are vital. However, it is also important to recognize that threatened species are part of complex social, ecological, economic and cultural systems, and to achieve successful outcomes requires consideration of indigenous peoples’ priorities, rights, and obligations and relationships with their traditionally owned land and sea.