Impacts of the Fair and Equitable Tobacco Reform Act of 2004 on Shareholders’ Wealth in the Tobacco Industry

This study examines the impact and efficiency of the design of the Fair and Equitable Tobacco Reform Act of 2004 in deregulating the tobacco production industry. Results offer a number of policy implications of which deregulation of an economically challenged industry can be achieved without the use of taxpayer funds.Tobacco Buyout, Tobacco Industry, Event Study, Agribusiness, Agricultural and Food Policy,

FRESH VEGETABLE PRICE LINKAGE BETWEEN GROWER/SHIPPERS, WHOLESALERS AND RETAILERS

This study focused on the transmission of price adjustments between grower/shippers and wholesalers and between wholesale handlers and retailers of nine fresh vegetables (only the results associated with bell peppers are reported in this paper). Results among the nine vegetable products were not consistent with respect to the magnitude of adjustments or the time periods involved in the adjustments. In response to wholesale price changes, upward price adjustments at the retail level occur more quickly than do downward price adjustments. Price transmission relationships also varied among the vegetable products between the wholesaler and grower. Overall, the results indicate that factors in addition to changes in upstream prices are impacting retailers' and wholesalers' pricing decisions.Demand and Price Analysis,

BIRCH: A user-oriented, locally-customizable, bioinformatics system

BACKGROUND: Molecular biologists need sophisticated analytical tools which often demand extensive computational resources. While finding, installing, and using these tools can be challenging, pipelining data from one program to the next is particularly awkward, especially when using web-based programs. At the same time, system administrators tasked with maintaining these tools do not always appreciate the needs of research biologists. RESULTS: BIRCH (Biological Research Computing Hierarchy) is an organizational framework for delivering bioinformatics resources to a user group, scaling from a single lab to a large institution. The BIRCH core distribution includes many popular bioinformatics programs, unified within the GDE (Genetic Data Environment) graphic interface. Of equal importance, BIRCH provides the system administrator with tools that simplify the job of managing a multiuser bioinformatics system across different platforms and operating systems. These include tools for integrating locally-installed programs and databases into BIRCH, and for customizing the local BIRCH system to meet the needs of the user base. BIRCH can also act as a front end to provide a unified view of already-existing collections of bioinformatics software. Documentation for the BIRCH and locally-added programs is merged in a hierarchical set of web pages. In addition to manual pages for individual programs, BIRCH tutorials employ step by step examples, with screen shots and sample files, to illustrate both the important theoretical and practical considerations behind complex analytical tasks. CONCLUSION: BIRCH provides a versatile organizational framework for managing software and databases, and making these accessible to a user base. Because of its network-centric design, BIRCH makes it possible for any user to do any task from anywhere

Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

Developmental trajectories of infants with multiplex family risk for Autism: a Baby Siblings Research Consortium Study

Importance: Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with different genetic etiologies. Prospective examination of familial-risk infants informs understanding of developmental trajectories preceding ASD diagnosis, potentially improving early detection. Objective: Compare outcomes and trajectories associated with varying familial risk for ASD across first 3 years of life. Design and Setting: Longitudinal, prospective observational study. Data from 11 sites in Baby Siblings Research Consortium (BSRC) database included. Data collected between 2003-2015. Infants followed for 3 years. Analyses conducted in 2018. Participants: Of initial 1,008 infants from BSRC database, 573 removed due to missing necessary data, diagnostic discrepancies, or only one older sibling. 435 younger siblings of children with ASD included; 355 from single-incidence families (1 sibling with ASD and 1+ sibling without ASD) and 80 from multiplex families (2+ siblings with ASD). No group differences in major demographics. Exposure: Number of ASD-siblings. Main Outcomes and Measures: Outcomes included ASD symptoms, cognitive abilities, and adaptive skills. Diagnosis (ASD/no-ASD) given at 36-month outcome. No-ASD group classified as atypical (developmental delays and/or social-communication concerns) or typical for some analyses. Generalized linear mixed models examined developmental trajectories by ASD outcome and familial-risk group. Results: In the 435 analyzed participants (age range at outcome: 32-43 months; 57% male), children from multiplex families were more likely than those from single-incidence families to 5 be classified as ASD (36% vs. 16%, p<.001) and less likely as typical (33% vs. 57%, p<.001), with similar rates of atypical classifications (31% vs. 27%, p=.49). No differences in ASD symptoms between multiplex and single-incidence groups, after controlling for ASD outcome (p=.18). During infancy, differences in cognitive and adaptive abilities observed based upon ASD outcome in single-incidence group only (ps<.001-.04). At 36 months, multiplex/no-ASD group had lower cognitive abilities than single-incidence/no-ASD group (p=.02), and multiplex had lower adaptive abilities than single-incidence, after controlling for ASD outcome (p=.02). Conclusions and Relevance: Infants with a multiplex family history of ASD should be monitored early and often and referred for early intervention at the first sign of concern. Direct examination of genetic contributions to neurodevelopmental phenotypes in infants with familial risk for ASD is needed

The Complete Genome Sequence of Escherichia coli EC958: A High Quality Reference Sequence for the Globally Disseminated Multidrug Resistant E. coli O25b:H4-ST131 Clone

Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific inversions in the tail fibre regions of prophages demonstrates the potential for this technology to reveal dynamic evolutionary mechanisms. E. coli EC958 belongs to the major subgroup of ST131 strains that produce the CTX-M-15 extended spectrum β-lactamase, are fluoroquinolone resistant and encode the fimH30 type 1 fimbrial adhesin. This subgroup includes the Indian strain NA114 and the North American strain JJ1886. A comparison of the genomes of EC958, JJ1886 and NA114 revealed that differences in the arrangement of genomic islands, prophages and other repetitive elements in the NA114 genome are not biologically relevant and are due to misassembly. The availability of a high quality uropathogenic E. coli ST131 genome provides a reference for understanding this multidrug resistant pathogen and will facilitate novel functional, comparative and clinical studies of the E. coli ST131 clonal lineage

Anger as “seeing red”: Evidence for a perceptual association

Metaphor representation theory contends that people conceptualise their non-perceptual states (e.g., emotion concepts) in perceptual terms. The present research extends this theory to colour manipulations and discrete emotional representations. Two experiments (N=265) examined whether a red font colour would facilitate anger conceptions, consistent with metaphors referring to anger to “seeing red”. Evidence for an implicit anger-red association was robust and emotionally discrete in nature. Further, Experiment 2 examined the directionality of such associations and found that they were asymmetrical: Anger categorisations were faster when a red font colour was involved, but redness categorisations were not faster when an anger-related word was involved. Implications for multiple literatures are discussed

Analysis of the Neurotoxin Complex Genes in Clostridium botulinum A1-A4 and B1 Strains: BoNT/A3, /Ba4 and /B1 Clusters Are Located within Plasmids

BACKGROUND: Clostridium botulinum and related clostridial species express extremely potent neurotoxins known as botulinum neurotoxins (BoNTs) that cause long-lasting, potentially fatal intoxications in humans and other mammals. The amino acid variation within the BoNT is used to categorize the species into seven immunologically distinct BoNT serotypes (A-G) which are further divided into subtypes. The BoNTs are located within two generally conserved gene arrangements known as botulinum progenitor complexes which encode toxin-associated proteins involved in toxin stability and expression. METHODOLOGY/PRINCIPAL FINDINGS: Because serotype A and B strains are responsible for the vast majority of human botulism cases worldwide, the location, arrangement and sequences of genes from eight different toxin complexes representing four different BoNT/A subtypes (BoNT/A1-Ba4) and one BoNT/B1 strain were examined. The bivalent Ba4 strain contained both the BoNT/A4 and BoNT/bvB toxin clusters. The arrangements of the BoNT/A3 and BoNT/A4 subtypes differed from the BoNT/A1 strains and were similar to those of BoNT/A2. However, unlike the BoNT/A2 subtype, the toxin complex genes of BoNT/A3 and BoNT/A4 were found within large plasmids and not within the chromosome. In the Ba4 strain, both BoNT toxin clusters (A4 and bivalent B) were located within the same 270 kb plasmid, separated by 97 kb. Complete genomic sequencing of the BoNT/B1 strain also revealed that its toxin complex genes were located within a 149 kb plasmid and the BoNT/A3 complex is within a 267 kb plasmid. CONCLUSIONS/SIGNIFICANCE: Despite their size differences and the BoNT genes they contain, the three plasmids containing these toxin cluster genes share significant sequence identity. The presence of partial insertion sequence (IS) elements, evidence of recombination/gene duplication events, and the discovery of the BoNT/A3, BoNT/Ba4 and BoNT/B1 toxin complex genes within plasmids illustrate the different mechanisms by which these genes move among diverse genetic backgrounds of C. botulinum

Genome-Wide Analysis of Transcriptional Reprogramming in Mouse Models of Acute Myeloid Leukaemia

Acute leukaemias are commonly caused by mutations that corrupt the transcriptional circuitry of haematopoietic stem/progenitor cells. However, the mechanisms underlying large-scale transcriptional reprogramming remain largely unknown. Here we investigated transcriptional reprogramming at genome-scale in mouse retroviral transplant models of acute myeloid leukaemia (AML) using both gene-expression profiling and ChIP-sequencing. We identified several thousand candidate regulatory regions with altered levels of histone acetylation that were characterised by differential distribution of consensus motifs for key haematopoietic transcription factors including Gata2, Gfi1 and Sfpi1/Pu.1. In particular, downregulation of Gata2 expression was mirrored by abundant GATA motifs in regions of reduced histone acetylation suggesting an important role in leukaemogenic transcriptional reprogramming. Forced re-expression of Gata2 was not compatible with sustained growth of leukaemic cells thus suggesting a previously unrecognised role for Gata2 in downregulation during the development of AML. Additionally, large scale human AML datasets revealed significantly higher expression of GATA2 in CD34+ cells from healthy controls compared with AML blast cells. The integrated genome-scale analysis applied in this study represents a valuable and widely applicable approach to study the transcriptional control of both normal and aberrant haematopoiesis and to identify critical factors responsible for transcriptional reprogramming in human cancer