An Interpretation of Late Quaternary Glacial Flow Indicators in the Baie des Chaleurs Region, Northern New Brunswick

A sequence of late Quaternary geologic events in northern New Brunswick is determined from striation analysis derived from published data, open file reports, and field research conducted by the authors since 1985. These data are integrated with clast provenance and clast fabric trend analysis, as well as information from other studies in the surrounding area. South of the Baie des Chaleurs, a complicated Late Wisconsinan glacial history is preserved in the form of erosive features including nailhead striae, miniature crag-and-tails, and various scars, striations, and fractures. The rarity of sedimentary deposits and datable materials precludes simple stratigraphie interpretation. Based on over 1,000 striation sites, we conclude four major phases of glacial flow affected the area during the Late Wisconsinan: 1) an early flow to the southeast which reflects local Appalachian ice; 2) a second phase of glacial flow to the east indicating a Laurentide ice influence in western New Brunswick; 3) a third phase of glacial flow to the north-northeast, which may represent ice response to drawdown in the Baie des Chaleurs; and 4) a final multidirectional flow indicating localized ice response during the last stages of Late Wisconsinan glaciation. The absence of Canadian Shield erratics in northern New Brunswick is explained in terms of ice streaming along the St. Lawrence channel beneath a southward-flowing Laurentide Ice Sheet. Basal ice debris (including Shield erratics) was apparently truncated and removed by the obliquely flowing ice stream, leaving relatively clean ice in the Ice Sheet as it entered Gaspésie and ultimately New Brunswick.On a déterminé la séquence des événements géologiques du Quaternaire supérieur survenus dans le nord du Nouveau-Brunswick à partir de l'analyse des stries tirée de diverses sources. Au sud de la baie des Chaleurs, l'évolution glaciaire complexe du Wisconsinien supérieur peut être retracée à partir des formes d'érosion glaciaire dont les clouures, les crag-and-tails miniatures, les cicatrices de toutes sortes, les stries et les fractures. La rareté des sédiments et des matériaux pouvant être datés excluent toute interprétation fondée sur la stratigraphie. En s'appuyant sur plus de 1000 sites de stries, on croit que la région a connu quatre épisodes glaciaires pendant le Wisconsinien supérieur: 1 ) le premier mouvement, de faible importance, s'est fait vers le SE en provenance des Appalaches; 2) le deuxième écoulement glaciaire vers PE démontre la force des glaces laurentidiennes au nord du Nouveau-Brunswick; 3) le troisième mouvement glaciaire vers le NNE pourrait être une réaction à l'affaissement qui s'est produit dans la baie des Chaleurs; 4) le dernier mouvement multidirectionnel s'est fait à partir de calottes localisées pendant les derniers stades de la glaciation wisconsinienne. On explique l'absence des blocs erratiques dans le nord du Nouveau-Brunswick par un écoulement des glaces le long du chenal laurentien interrompant l'Inlandsis laurentidien s'écoulant vers le sud. Les débris glaciaires de fond (y compris les blocs erratiques du Bouclier) ont apparemment été tronqués et enlevés par un courant glaciaire oblique, épurant ainsi la glace qui pénétrait en Gaspésie, puis au Nouveau-Brunswick.Een Interpretatie van Laat-glaciale Ijsbewegingsindicaties in de Chaleur Bay Regio, Noord New Brunswick. De Kwartair geologische kartering van noord New Brunswick begon met de studies van Robert Chalmers aan het einde van de 19e eeuw. Sindsdien zijn verschillende pogingen gedaan om de glaciale geschiedenis van dit gebied te ontravelen en uiteindelijk zijn Chalmers ideeen herontdekt en aangepast aan moderne theorien en modellen van glaciale processen en isostasie. De afwezigheid van stratigrafische secties en de aanwezigheid van vêle glaciale erosieve en morphologische vormen heeft geleid tot de ontwikkeling van een "erosie-stratigrafie ". Deze informatie wordt gesteund door till lithologische en ges-teente orientatie studies. Het resultaat van dit gedetailleerde karterings project is de her-kenning van 4 verschillende ijs-bewegingen. Datering van deze gebeurtenissen is een probleem vanwege een gebrek aan dateer-bare materialen. Een eerste zuidoostelijke ijsbeweging is geregistreerd in het oostelijke deel van het gebied en in de Chaleur Coastal Plain. De tweede en sterkste gebeurtenis geeft een oostwaartse ijsbeweging te zien, die waarschijnlijk gedurende het gehele Wisconsinan (Weichselien) en mogelijk het gehele Pleistoceen van belang kan zijn geweest. Een derde ijsbeweging is in noord-oostelijke richt-ing in de Baie des Chaleurs. In een latere fase, lokale ijsbewegingen vonden plaats in verschillende richtingen vanaf de hooglanden en mogelijk vanuit Baie des Chaleurs. Er is een poging gedaan deze gebeurtenissen in een régionale context te plaatsen, waarin de interactie van de Laurentide Ice Sheet met het Appalachian Ice Complex en het concept van een Laurentian ijsstroomkanaal centraal staan

Medication adherence in patients with myotonic dystrophy and facioscapulohumeral muscular dystrophy

Myotonic dystrophy (DM) and facioscapulohumeral muscular dystrophy (FSHD) are the two most common adult muscular dystrophies and have progressive and often disabling manifestations. Higher levels of medication adherence lead to better health outcomes, especially important to patients with DM and FSHD because of their multisystem manifestations and complexity of care. However, medication adherence has not previously been studied in a large cohort of DM type 1 (DM1), DM type 2 (DM2), and FSHD patients. The purpose of our study was to survey medication adherence and disease manifestations in patients enrolled in the NIH-supported National DM and FSHD Registry. The study was completed by 110 DM1, 49 DM2, and 193 FSHD patients. Notable comorbidities were hypertension in FSHD (44 %) and DM2 (37 %), gastroesophageal reflux disease in DM1 (24 %) and DM2 (31 %) and arrhythmias (29 %) and thyroid disease (20 %) in DM1. Each group reported high levels of adherence based on regimen complexity, medication costs, health literacy, side effect profile, and their beliefs about treatment. Only dysphagia in DM1 was reported to significantly impact medication adherence. Approximately 35 % of study patients reported polypharmacy (taking 6 or more medications). Of the patients with polypharmacy, the DM1 cohort was significantly younger (mean 55.0 years) compared to DM2 (59.0 years) and FSHD (63.2 years), and had shorter disease duration (mean 26 years) compared to FSHD (26.8 years) and DM2 (34.8 years). Future research is needed to assess techniques to ease pill swallowing in DM1 and to monitor polypharmacy and potential drug interactions in DM and FSHD

A correlated-polaron electronic propagator: open electronic dynamics beyond the Born-Oppenheimer approximation

In this work we develop a theory of correlated many-electron dynamics dressed by the presence of a finite-temperature harmonic bath. The theory is based on the ab-initio Hamiltonian, and thus well-defined apart from any phenomenological choice of collective basis states or electronic coupling model. The equation-of-motion includes some bath effects non-perturbatively, and can be used to simulate line- shapes beyond the Markovian approximation and open electronic dynamics which are subjects of renewed recent interest. Energy conversion and transport depend critically on the ratio of electron-electron coupling to bath-electron coupling, which is a fitted parameter if a phenomenological basis of many-electron states is used to develop an electronic equation of motion. Since the present work doesn't appeal to any such basis, it avoids this ambiguity. The new theory produces a level of detail beyond the adiabatic Born-Oppenheimer states, but with cost scaling like the Born-Oppenheimer approach. While developing this model we have also applied the time-convolutionless perturbation theory to correlated molecular excitations for the first time. Resonant response properties are given by the formalism without phenomenological parameters. Example propagations with a developmental code are given demonstrating the treatment of electron-correlation in absorption spectra, vibronic structure, and decay in an open system.Comment: 25 pages 7 figure

BamView: viewing mapped read alignment data in the context of the reference sequence

Summary: BamView is an interactive Java application for visualizing the large amounts of data stored for sequence reads which are aligned against a reference genome sequence. It supports the BAM (Binary Alignment/Map) format. It can be used in a number of contexts including SNP calling and structural annotation. BamView has also been integrated into Artemis so that the reads can be viewed in the context of the nucleotide sequence and genomic features

Whole Genome Sequence Analysis of a Large Isoniazid-Resistant Tuberculosis Outbreak in London: A Retrospective Observational Study

BACKGROUND: A large isoniazid-resistant tuberculosis outbreak centred on London, United Kingdom, has been ongoing since 1995. The aim of this study was to investigate the power and value of whole genome sequencing (WGS) to resolve the transmission network compared to current molecular strain typing approaches, including analysis of intra-host diversity within a specimen, across body sites, and over time, with identification of genetic factors underlying the epidemiological success of this cluster. METHODS AND FINDINGS: We sequenced 344 outbreak isolates from individual patients collected over 14 y (2 February 1998-22 June 2012). This demonstrated that 96 (27.9%) were indistinguishable, and only one differed from this major clone by more than five single nucleotide polymorphisms (SNPs). The maximum number of SNPs between any pair of isolates was nine SNPs, and the modal distance between isolates was two SNPs. WGS was able to reveal the direction of transmission of tuberculosis in 16 cases within the outbreak (4.7%), including within a multidrug-resistant cluster that carried a rare rpoB mutation associated with rifampicin resistance. Eleven longitudinal pairs of patient pulmonary isolates collected up to 48 mo apart differed from each other by between zero and four SNPs. Extrapulmonary dissemination resulted in acquisition of a SNP in two of five cases. WGS analysis of 27 individual colonies cultured from a single patient specimen revealed ten loci differed amongst them, with a maximum distance between any pair of six SNPs. A limitation of this study, as in previous studies, is that indels and SNPs in repetitive regions were not assessed due to the difficulty in reliably determining this variation. CONCLUSIONS: Our study suggests that (1) certain paradigms need to be revised, such as the 12 SNP distance as the gold standard upper threshold to identify plausible transmissions; (2) WGS technology is helpful to rule out the possibility of direct transmission when isolates are separated by a substantial number of SNPs; (3) the concept of a transmission chain or network may not be useful in institutional or household settings; (4) the practice of isolating single colonies prior to sequencing is likely to lead to an overestimation of the number of SNPs between cases resulting from direct transmission; and (5) despite appreciable genomic diversity within a host, transmission of tuberculosis rarely results in minority variants becoming dominant. Thus, whilst WGS provided some increased resolution over variable number tandem repeat (VNTR)-based clustering, it was insufficient for inferring transmission in the majority of cases

DNAPlotter: circular and linear interactive genome visualization

Summary: DNAPlotter is an interactive Java application for generating circular and linear representations of genomes. Making use of the Artemis libraries to provide a user-friendly method of loading in sequence files (EMBL, GenBank, GFF) as well as data from relational databases, it filters features of interest to display on separate user-definable tracks. It can be used to produce publication quality images for papers or web pages

Improved Prediction of Bacterial Genotype-Phenotype Associations Using Interpretable Pangenome-Spanning Regressions

Discovery of genetic variants underlying bacterial phenotypes and the prediction of phenotypes such as antibiotic resistance are fundamental tasks in bacterial genomics. Genome-wide association study (GWAS) methods have been applied to study these relations, but the plastic nature of bacterial genomes and the clonal structure of bacterial populations creates challenges. We introduce an alignment-free method which finds sets of loci associated with bacterial phenotypes, quantifies the total effect of genetics on the phenotype, and allows accurate phenotype prediction, all within a single computationally scalable joint modeling framework. Genetic variants covering the entire pangenome are compactly represented by extended DNA sequence words known as unitigs, and model fitting is achieved using elastic net penalization, an extension of standard multiple regression. Using an extensive set of state-of-the-art bacterial population genomic data sets, we demonstrate that our approach performs accurate phenotype prediction, comparable to popular machine learning methods, while retaining both interpretability and computational efficiency. Compared to those of previous approaches, which test each genotype-phenotype association separately for each variant and apply a significance threshold, the variants selected by our joint modeling approach overlap substantially. IMPORTANCE Being able to identify the genetic variants responsible for specific bacterial phenotypes has been the goal of bacterial genetics since its inception and is fundamental to our current level of understanding of bacteria. This identification has been based primarily on painstaking experimentation, but the availability of large data sets of whole genomes with associated phenotype metadata promises to revolutionize this approach, not least for important clinical phenotypes that are not amenable to laboratory analysis. These models of phenotype-genotype association can in the future be used for rapid prediction of clinically important phenotypes such as antibiotic resistance and virulence by rapid-turnaround or point-of-care tests. However, despite much effort being put into adapting genome-wide association study (GWAS) approaches to cope with bacterium-specific problems, such as strong population structure and horizontal gene exchange, current approaches are not yet optimal. We describe a method that advances methodology for both association and generation of portable prediction models.Peer reviewe

Re-annotation and re-analysis of the Campylobacter jejuni NCTC11168 genome sequence

BACKGROUND: Campylobacter jejuni is the leading bacterial cause of human gastroenteritis in the developed world. To improve our understanding of this important human pathogen, the C. jejuni NCTC11168 genome was sequenced and published in 2000. The original annotation was a milestone in Campylobacter research, but is outdated. We now describe the complete re-annotation and re-analysis of the C. jejuni NCTC11168 genome using current database information, novel tools and annotation techniques not used during the original annotation. RESULTS: Re-annotation was carried out using sequence database searches such as FASTA, along with programs such as TMHMM for additional support. The re-annotation also utilises sequence data from additional Campylobacter strains and species not available during the original annotation. Re-annotation was accompanied by a full literature search that was incorporated into the updated EMBL file [EMBL: AL111168]. The C. jejuni NCTC11168 re-annotation reduced the total number of coding sequences from 1654 to 1643, of which 90.0% have additional information regarding the identification of new motifs and/or relevant literature. Re-annotation has led to 18.2% of coding sequence product functions being revised. CONCLUSIONS: Major updates were made to genes involved in the biosynthesis of important surface structures such as lipooligosaccharide, capsule and both O- and N-linked glycosylation. This re-annotation will be a key resource for Campylobacter research and will also provide a prototype for the re-annotation and re-interpretation of other bacterial genomes

Dominant Role of Nucleotide Substitution in the Diversification of Serotype 3 Pneumococci over Decades and during a Single Infection

Streptococcus pneumoniae of serotype 3 possess a mucoid capsule and cause disease associated with high mortality rates relative to other pneumococci. Phylogenetic analysis of a complete reference genome and 81 draft sequences from clonal complex 180, the predominant serotype 3 clone in much of the world, found most sampled isolates belonged to a clade affected by few diversifying recombinations. However, other isolates indicate significant genetic variation has accumulated over the clonal complex’s entire history. Two closely related genomes, one from the blood and another from the cerebrospinal fluid, were obtained from a patient with meningitis. The pair differed in their behaviour in a mouse model of disease and in their susceptibility to antimicrobials, with at least some of these changes attributable to a mutation that upregulated the patAB efflux pump. This indicates clinically important phenotypic variation can accumulate rapidly through small alterations to the genotype

Genomic Profiling Reveals Distinct Routes To Complement Resistance in Klebsiella pneumoniae.

The serum complement system is a first line of defense against bacterial invaders. Resistance to killing by serum enhances the capacity of Klebsiella pneumoniae to cause infection, but it is an incompletely understood virulence trait. Identifying and characterizing the factors responsible for preventing activation of, and killing by, serum complement could inform new approaches to treatment of K. pneumoniae infections. Here, we used functional genomic profiling to define the genetic basis of complement resistance in four diverse serum-resistant K. pneumoniae strains (NTUH-K2044, B5055, ATCC 43816, and RH201207), and explored their recognition by key complement components. More than 90 genes contributed to resistance in one or more strains, but only three, rfaH, lpp, and arnD, were common to all four strains. Deletion of the antiterminator rfaH, which controls the expression of capsule and O side chains, resulted in dramatic complement resistance reductions in all strains. The murein lipoprotein gene lpp promoted capsule retention through a mechanism dependent on its C-terminal lysine residue; its deletion led to modest reductions in complement resistance. Binding experiments with the complement components C3b and C5b-9 showed that the underlying mechanism of evasion varied in the four strains: B5055 and NTUH-K2044 appeared to bypass recognition by complement entirely, while ATCC 43816 and RH201207 were able to resist killing despite being associated with substantial levels of C5b-9. All rfaH and lpp mutants bound C3b and C5b-9 in large quantities. Our findings show that, even among this small selection of isolates, K. pneumoniae adopts differing mechanisms and utilizes distinct gene sets to avoid complement attack