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1.
bioRxiv ; 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37398483

ABSTRACT

We describe the epidemiology and clinical characteristics of 29 patients with cancer and diarrhea in whom Enteroaggregative Escherichia coli (EAEC) was initially identified by GI BioFire panel multiplex. E. coli strains were successfully isolated from fecal cultures in 14 of 29 patients. Six of the 14 strains were identified as EAEC and 8 belonged to other diverse E. coli groups of unknown pathogenesis. We investigated these strains by their adherence to human intestinal organoids, cytotoxic responses, antibiotic resistance profile, full sequencing of their genomes, and annotation of their functional virulome. Interestingly, we discovered novel and enhanced adherence and aggregative patterns for several diarrheagenic pathotypes that were not previously seen when co-cultured with immortalized cell lines. EAEC isolates displayed exceptional adherence and aggregation to human colonoids compared not only to diverse GI E. coli , but also compared to prototype strains of other diarrheagenic E. coli . Some of the diverse E. coli strains that could not be classified as a conventional pathotype also showed an enhanced aggregative and cytotoxic response. Notably, we found a high carriage rate of antibiotic resistance genes in both EAEC strains and diverse GI E. coli isolates and observed a positive correlation between adherence to colonoids and the number of metal acquisition genes carried in both EAEC and the diverse E. coli strains. This work indicates that E. coli from cancer patients constitute strains of remarkable pathotypic and genomic divergence, including strains of unknown disease etiology with unique virulomes. Future studies will allow for the opportunity to re-define E. coli pathotypes with greater diagnostic accuracy and into more clinically relevant groupings.

2.
J Trauma Nurs ; 30(4): 228-234, 2023.
Article in English | MEDLINE | ID: mdl-37417674

ABSTRACT

BACKGROUND: Although the role of a dedicated trauma nurse has been implemented in an urban setting, it has not been studied in the rural trauma setting. We instituted a trauma resuscitation emergency care (TREC) nurse role to respond to trauma activations at our rural trauma center. OBJECTIVE: This study aims to determine the impact of TREC nurse deployment on the timeliness of resuscitation interventions in trauma activations. METHODS: This pre- and postintervention study at a rural Level I trauma center compared the time to resuscitation interventions before (August 2018 to July 2019) and after (August 2019 to July 2020) deploying TREC nurses to trauma activations. RESULTS: A total of 2,593 participants were studied, of which 1,153 (44%) were in the pre-TREC group and 1,440 (56%) in the post-TREC group. After TREC deployment, the median (interquartile range [IQR]) emergency department times within the first hour decreased from 45 (31.23-53) to 35 (16-51) min ( p = .013). The median (IQR) time to the operating room within the first hour decreased from 46 (37-52) to 29 (12-46) min ( p = .001), and within the first 2 hr, decreased from 59 (43.8-86) to 48 (23-72) min ( p = .014). CONCLUSION: Our study found that TREC nurse deployment improved resuscitation intervention timeliness during the first 2 hr (early phase) of trauma activations.


Subject(s)
Emergency Medical Services , Wounds and Injuries , Humans , Trauma Centers , Emergency Service, Hospital , Resuscitation , Nurse's Role , Wounds and Injuries/diagnosis , Wounds and Injuries/therapy
3.
PLoS Pathog ; 17(1): e1009182, 2021 01.
Article in English | MEDLINE | ID: mdl-33406160

ABSTRACT

Streptococcus gallolyticus subspecies gallolyticus (Sgg) has a strong clinical association with colorectal cancer (CRC) and actively promotes the development of colon tumors. However, the molecular determinants involved in Sgg pathogenicity in the gut are unknown. Bacterial type VII secretion systems (T7SS) mediate pathogen interactions with their host and are important for virulence in pathogenic mycobacteria and Staphylococcus aureus. Through genome analysis, we identified a locus in Sgg strain TX20005 that encodes a putative type VII secretion system (designated as SggT7SST05). We showed that core genes within the SggT7SST05 locus are expressed in vitro and in the colon of mice. Western blot analysis showed that SggEsxA, a protein predicted to be a T7SS secretion substrate, is detected in the bacterial culture supernatant, indicating that this SggT7SST05 is functional. Deletion of SggT7SST05 (TX20005Δesx) resulted in impaired bacterial adherence to HT29 cells and abolished the ability of Sgg to stimulate HT29 cell proliferation. Analysis of bacterial culture supernatants suggest that SggT7SST05-secreted factors are responsible for the pro-proliferative activity of Sgg, whereas Sgg adherence to host cells requires both SggT7SST05-secreted and bacterial surface-associated factors. In a murine gut colonization model, TX20005Δesx showed significantly reduced colonization compared to the parent strain. Furthermore, in a mouse model of CRC, mice exposed to TX20005 had a significantly higher tumor burden compared to saline-treated mice, whereas those exposed to TX20005Δesx did not. Examination of the Sgg load in the colon in the CRC model suggests that SggT7SST05-mediated activities are directly involved in the promotion of colon tumors. Taken together, these results reveal SggT7SST05 as a previously unrecognized pathogenicity determinant for Sgg colonization of the colon and promotion of colon tumors.


Subject(s)
Cell Proliferation , Colonic Neoplasms/pathology , Gastrointestinal Microbiome , Gastrointestinal Tract/microbiology , Streptococcal Infections/microbiology , Streptococcus gallolyticus subspecies gallolyticus/physiology , Type VII Secretion Systems/metabolism , Animals , Colonic Neoplasms/chemically induced , Colonic Neoplasms/microbiology , Humans , Mice , Mice, Inbred A , Streptococcal Infections/metabolism
4.
Front Microbiol ; 11: 887, 2020.
Article in English | MEDLINE | ID: mdl-32508769

ABSTRACT

Chloroviruses (family Phycodnaviridae) infect eukaryotic, freshwater, unicellular green algae. A unique feature of these viruses is an abundance of DNA methyltransferases, with isolates dedicating up to 4.5% of their protein coding potential to these genes. This diversity highlights just one of the long-standing values of the chlorovirus model system; where group-wide epigenomic characterization might begin to elucidate the function(s) of DNA methylation in large dsDNA viruses. We characterized DNA modifications in the prototype chlorovirus, PBCV-1, using single-molecule real time (SMRT) sequencing (aka PacBio). Results were compared to total available sites predicted in silico based on DNA sequence alone. SMRT-software detected N6-methyl-adenine (m6A) at GATC and CATG recognition sites, motifs previously shown to be targeted by PBCV-1 DNA methyltransferases M.CviAI and M. CviAII, respectively. At the same time, PacBio analyses indicated that 10.9% of the PBCV-1 genome had large interpulse duration ratio (ipdRatio) values, the primary metric for DNA modification identification. These events represent 20.6x more sites than can be accounted for by all available adenines in GATC and CATG motifs, suggesting base or backbone modifications other than methylation might be present. To define methylation stability, we cross-compared methylation status of each GATC and CATG sequence in three biological replicates and found ∼81% of sites were stably methylated, while ∼2% consistently lack methylation. The remaining 17% of sites were stochastically methylated. When methylation status was analyzed for both strands of each target, we show that palindromes existed in completely non-methylated states, fully-methylated states, or hemi-methylated states, though GATC sites more often lack methylation than CATG sequences. Given that both sequences are targeted by not just methyltransferases, but by restriction endonucleases that are together encoded by PBCV-1 as virus-originating restriction modification (RM) systems, there is strong selective pressure to modify all target sites. The finding that most instances of non-methylation are associated with hemi-methylation is congruent with observations that hemi-methylated palindromes are resistant to cleavage by restriction endonucleases. However, sites where hemi-methylation is conserved might represent a unique regulatory function for PBCV-1. This study serves as a baseline for future investigation into the epigenomics of chloroviruses and their giant virus relatives.

5.
J Endod ; 43(9S): S87-S94, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28844308

ABSTRACT

The balance between the immune/inflammatory and regenerative responses in the diseased pulp is central to the clinical outcome, and this response is unique within the body because of its tissue site. Cariogenic bacteria invade the dentin and pulp tissues, triggering molecular and cellular events dependent on the disease stage. At the early onset, odontoblasts respond to bacterial components in an attempt to protect the tooth's hard and soft tissues and limit disease progression. However, as disease advances, the odontoblasts die, and cells central to the pulp core, including resident immune cells, pulpal fibroblasts, endothelial cells, and stem cells, respond to the bacterial challenge via their expression of a range of pattern recognition receptors that identify pathogen-associated molecular patterns. Subsequently, recruitment and activation occurs of a range of immune cell types, including neutrophils, macrophages, and T and B cells, which are attracted to the diseased site by cytokine/chemokine chemotactic gradients initially generated by resident pulpal cells. Although these cells aim to disinfect the tooth, their extravasation, migration, and antibacterial activity (eg, release of reactive oxygen species [ROS]) along with the bacterial toxins cause pulp damage and impede tissue regeneration processes. Recently, a novel bacterial killing mechanism termed neutrophil extracellular traps (NETs) has also been described that uses ROS signaling and results in cellular DNA extrusion. The NETs are decorated with antimicrobial peptides (AMPs), and their interaction with bacteria results in microbial entrapment and death. Recent data show that NETs can be stimulated by bacteria associated with endodontic infections, and they may be present in inflamed pulp tissue. Interestingly, some bacteria associated with pulpal infections express deoxyribonuclease enzymes, which may enable their evasion of NETs. Furthermore, although NETs aim to localize and kill invading bacteria using AMPs and histones, limiting the spread of the infection, data also indicate that NETs can exacerbate inflammation and their components are cytotoxic. This review considers the potential role of NETs within pulpal infections and how these structures may influence the pulp's vitality and regenerative responses.


Subject(s)
Bacterial Infections/immunology , Dental Pulp/physiology , Dentin/physiology , Extracellular Traps/physiology , Regeneration , Humans , Inflammation/immunology
6.
Genome Announc ; 5(30)2017 Jul 27.
Article in English | MEDLINE | ID: mdl-28751405

ABSTRACT

Vibrio gazogenes ATCC 43942 has the potential to synthesize a plethora of metabolites which are of clinical and agricultural significance in response to environmental triggers. The complete genomic sequence of Vibrio gazogenes ATCC 43942 is reported herein, contributing to the knowledge base of strains in the Vibrio genus.

7.
Hosp Pediatr ; 7(4): 225-231, 2017 04.
Article in English | MEDLINE | ID: mdl-28336579

ABSTRACT

BACKGROUND AND OBJECTIVES: Major adverse events (AEs) related to pediatric deep sedation occur at a low frequency but can be of high acuity. The high volume of deep sedations performed by 3 departments at our institution provided an opportunity to reduce variability and increase safety through implementation of a procedural sedation safety checklist. We hypothesized that implementation of a checklist would improve compliance of critical safety elements (CSEs) (primary outcome variable) and reduce the sedation-related AE rate (secondary outcome variable). METHODS: This process improvement project was divided into 5 phases: a retrospective analysis to assess variability in capture of CSE within 3 departments that perform deep sedation and the association between noncapture of CSE and AE occurrence (phase 1), design of the checklist and trial in simulation (phase 2), provider education (phase 3), implementation and interim analysis of checklist completion (phase 4), and final analysis of completion and impact on outcome (phase 5). RESULTS: We demonstrated interdepartmental variability in compliance with CSE completion prechecklist implementation, and we identified elements associated with AEs. Completion of provider education was 100% in all 3 departments. Final analysis showed a checklist completion rate of 75%, and its use significantly improved capture of several critical safety elements. Its use did not significantly reduce AEs (P = .105). CONCLUSIONS: This study demonstrates that the implementation of a sedation checklist improved process adherence and capture of critical safety elements; however, it failed to show a significant reduction in sedation-related AEs.


Subject(s)
Checklist , Deep Sedation/adverse effects , Patient Safety , Risk Reduction Behavior , Child , Humans , Medical Staff, Hospital/education , Nursing Staff, Hospital/education , Ohio , Program Evaluation
8.
Genome Announc ; 4(2)2016 Apr 07.
Article in English | MEDLINE | ID: mdl-27056234

ABSTRACT

Streptococcus mitisfrequently causes invasive infections in neutropenic cancer patients, with a subset of patients developing viridans group streptococcal (VGS) shock syndrome. We report here the first complete genome sequence ofS. mitisstrain SVGS_061, which caused VGS shock syndrome, to help elucidate the pathogenesis of severe VGS infection.

9.
Int Orthop ; 40(3): 459-64, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26130288

ABSTRACT

PURPOSE: Two-stage revision hip arthroplasty using an antibiotic-loaded spacer is the most widely performed procedure for infected hip arthroplasties. The clinical outcome of this type of surgery compared with aseptic joint revision with exchange of femoral and acetabular components is still controversial due to the relative lack of medium- to long-term follow-up. Therefore, we analysed clinical and radiological outcomes of septic two-stage revisions compared with aseptic hip revision surgeries. METHODS: In this retrospective study we assessed 82 consecutive patients who underwent two-stage revision for septic total hip (45 patients) or one-stage aseptic revision arthroplasty (37 patients). The average follow-up was 53 months for the aseptic group and 55 months for the septic group. For clinical evaluation, we used the Harris Hip Score (HHS) and the Merle d'Aubigné and Postel score. The postoperative pain level was determined with the visual analogue pain scale. RESULTS: The surgeries were performed 124 months (aseptic group) and 119 months (septic group) after primary total hip arthroplasty on average. The main indications for aseptic revision surgeries were aseptic loosening (96%), dislocation (2.2%), and periprosthetic fracture (2.2%). In the clinical outcome patients achieved 75.5 points in the aseptic group and 73.4 points in the septic group in the Harris Hip Score. The Merle d'Aubigné and Postel Score revealed 12.5 points for the aseptic group and 13.1 points for the septic group. Mean level of persisting pain was 0.8 (aseptic group) and 0.4 (septic group) on the visual analogue scale (VAS). Overall survival in the aseptic group was 85.6% at 9.8 years 82.7% at 10.1 years for the septic group, with a repeat revision rate of 8.1% and 6.7%, respectively. CONCLUSIONS: Performing aseptic acetabular and femoral revision hip arthroplasty showed equal clinical outcomes in relation to septic two-stage revision hip surgeries. Our results showed a tendency for better outcome in comparison with the information given in the literature for septic and nonseptic exchange arthroplasties, including a lower rate of re-revisions.


Subject(s)
Arthroplasty, Replacement, Hip/methods , Postoperative Complications , Prosthesis-Related Infections/surgery , Reoperation/methods , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip/adverse effects , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain Measurement , Prosthesis Failure , Retrospective Studies , Treatment Outcome
10.
Nature ; 527(7579): 459-65, 2015 Nov 26.
Article in English | MEDLINE | ID: mdl-26580012

ABSTRACT

Acorn worms, also known as enteropneust (literally, 'gut-breathing') hemichordates, are marine invertebrates that share features with echinoderms and chordates. Together, these three phyla comprise the deuterostomes. Here we report the draft genome sequences of two acorn worms, Saccoglossus kowalevskii and Ptychodera flava. By comparing them with diverse bilaterian genomes, we identify shared traits that were probably inherited from the last common deuterostome ancestor, and then explore evolutionary trajectories leading from this ancestor to hemichordates, echinoderms and chordates. The hemichordate genomes exhibit extensive conserved synteny with amphioxus and other bilaterians, and deeply conserved non-coding sequences that are candidates for conserved gene-regulatory elements. Notably, hemichordates possess a deuterostome-specific genomic cluster of four ordered transcription factor genes, the expression of which is associated with the development of pharyngeal 'gill' slits, the foremost morphological innovation of early deuterostomes, and is probably central to their filter-feeding lifestyle. Comparative analysis reveals numerous deuterostome-specific gene novelties, including genes found in deuterostomes and marine microbes, but not other animals. The putative functions of these genes can be linked to physiological, metabolic and developmental specializations of the filter-feeding ancestor.


Subject(s)
Chordata, Nonvertebrate/genetics , Evolution, Molecular , Genome/genetics , Animals , Chordata, Nonvertebrate/classification , Conserved Sequence/genetics , Echinodermata/classification , Echinodermata/genetics , Multigene Family/genetics , Phylogeny , Signal Transduction , Synteny/genetics , Transforming Growth Factor beta
11.
Proc Natl Acad Sci U S A ; 112(20): 6431-6, 2015 May 19.
Article in English | MEDLINE | ID: mdl-25941374

ABSTRACT

The molecular mechanisms underlying pathogen emergence in humans is a critical but poorly understood area of microbiologic investigation. Serotype V group B Streptococcus (GBS) was first isolated from humans in 1975, and rates of invasive serotype V GBS disease significantly increased starting in the early 1990s. We found that 210 of 229 serotype V GBS strains (92%) isolated from the bloodstream of nonpregnant adults in the United States and Canada between 1992 and 2013 were multilocus sequence type (ST) 1. Elucidation of the complete genome of a 1992 ST-1 strain revealed that this strain had the highest homology with a GBS strain causing cow mastitis and that the 1992 ST-1 strain differed from serotype V strains isolated in the late 1970s by acquisition of cell surface proteins and antimicrobial resistance determinants. Whole-genome comparison of 202 invasive ST-1 strains detected significant recombination in only eight strains. The remaining 194 strains differed by an average of 97 SNPs. Phylogenetic analysis revealed a temporally dependent mode of genetic diversification consistent with the emergence in the 1990s of ST-1 GBS as major agents of human disease. Thirty-one loci were identified as being under positive selective pressure, and mutations at loci encoding polysaccharide capsule production proteins, regulators of pilus expression, and two-component gene regulatory systems were shown to affect the bacterial phenotype. These data reveal that phenotypic diversity among ST-1 GBS is mainly driven by small genetic changes rather than extensive recombination, thereby extending knowledge into how pathogens adapt to humans.


Subject(s)
Adaptation, Biological/genetics , Biological Evolution , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/microbiology , Streptococcus agalactiae/genetics , Adult , Base Sequence , Cluster Analysis , Genome, Bacterial/genetics , Humans , Likelihood Functions , Models, Genetic , Molecular Sequence Data , Ontario/epidemiology , Phylogeny , Polymorphism, Single Nucleotide/genetics , Sequence Analysis, DNA , Serogroup , Species Specificity , Texas/epidemiology
12.
Curr Biol ; 25(5): 613-20, 2015 Mar 02.
Article in English | MEDLINE | ID: mdl-25660540

ABSTRACT

Gall-forming arthropods are highly specialized herbivores that, in combination with their hosts, produce extended phenotypes with unique morphologies [1]. Many are economically important, and others have improved our understanding of ecology and adaptive radiation [2]. However, the mechanisms that these arthropods use to induce plant galls are poorly understood. We sequenced the genome of the Hessian fly (Mayetiola destructor; Diptera: Cecidomyiidae), a plant parasitic gall midge and a pest of wheat (Triticum spp.), with the aim of identifying genic modifications that contribute to its plant-parasitic lifestyle. Among several adaptive modifications, we discovered an expansive reservoir of potential effector proteins. Nearly 5% of the 20,163 predicted gene models matched putative effector gene transcripts present in the M. destructor larval salivary gland. Another 466 putative effectors were discovered among the genes that have no sequence similarities in other organisms. The largest known arthropod gene family (family SSGP-71) was also discovered within the effector reservoir. SSGP-71 proteins lack sequence homologies to other proteins, but their structures resemble both ubiquitin E3 ligases in plants and E3-ligase-mimicking effectors in plant pathogenic bacteria. SSGP-71 proteins and wheat Skp proteins interact in vivo. Mutations in different SSGP-71 genes avoid the effector-triggered immunity that is directed by the wheat resistance genes H6 and H9. Results point to effectors as the agents responsible for arthropod-induced plant gall formation.


Subject(s)
Chromosomes/genetics , Diptera/genetics , Multigene Family/genetics , Phylogeny , Plant Tumors/genetics , Triticum/parasitology , Adaptation, Biological/genetics , Amino Acid Sequence , Animals , Base Sequence , Diptera/metabolism , Larva/metabolism , Models, Genetic , Molecular Sequence Data , Sequence Analysis, DNA , Sequence Homology , Sexual Behavior, Animal/physiology , Two-Hybrid System Techniques , Ubiquitin-Protein Ligases/genetics
13.
Int Orthop ; 39(9): 1709-13, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25690924

ABSTRACT

PURPOSE: Revision hip arthroplasty using a modular tapered design gives the possibility for customising the prostheses to the individual anatomy intra-operatively. The success of this kind of surgery is still controversial due to the relative lack of medium- to long-term follow-up. Therefore we analysed the clinical and radiological outcome of the modular MRP-TITAN stem with diaphyseal fixation in revision hip surgery. METHODS: In this retrospective study we included 136 consecutive patients with MRP-TITAN stem implanted during revision hip arthroplasty. The average follow-up was 55 months. For clinical evaluation we used the Harris Hip Score and the Merle d'Aubigné and Postel score. The health-related quality of life was determined with the visual analogue pain scale. RESULTS: The surgeries were performed 109 months after primary total hip arthroplasty on average. The main indications for the MRP-TITAN revision stem were aseptic loosening, infection, and periprosthetic fracture. In the clinical outcome, patients achieved 75.1 points in the Harris Hip Score and 14.4 points in the Merle d'Aubigné and Postel Score. Mean level of persisting pain was 0.7 (VAS). The overall survival of the MRP stem in revision hip arthroplasty revealed 85.6% survival at 9.75 years' follow-up with a repeat revision rate of 6.8%. CONCLUSIONS: Performing revision hip arthroplasty using the MRP-TITAN stem revealed a good clinical outcome. There is a tendency for better results in comparison with the information given in literature for cementless modular revision stems including a lower rate in re-revisions.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Hip Joint/surgery , Hip Prosthesis/adverse effects , Joint Diseases/surgery , Aged , Aged, 80 and over , Biocompatible Materials , Female , Humans , Male , Middle Aged , Pain Measurement , Periprosthetic Fractures/etiology , Periprosthetic Fractures/surgery , Prosthesis Design , Prosthesis Failure , Prosthesis-Related Infections/etiology , Prosthesis-Related Infections/surgery , Quality of Life , Reoperation , Retrospective Studies , Titanium , Treatment Outcome
14.
Int Orthop ; 39(6): 1093-7, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25416121

ABSTRACT

PURPOSE: Total knee arthroplasty using a modular design gives the possibility for an isolated exchange of the tibial polyethylene insert in patients with failed total knee arthroplasty. The success of this kind of surgery is still controversial. We analysed the clinical outcome after isolated tibial polyethylene insert exchange. METHODS: In this retrospective study we included 62 consecutive patients with an isolated tibial polyethylene insert exchange at our institution. The average follow-up was 35 months. For clinical evaluation we used the Oxford Knee score, the Knee Society score, the Turba score, and the Kujala score. The health-related quality of life was determined with the SF-36 score and the visual analogue pain scale. RESULTS: The operations were performed 73 months after primary total knee arthroplasty on average. The main reasons for isolated tibial polyethylene insert exchange were instability and wear. In the clinical outcome patients achieved 31.5 points in the Oxford Knee score, 120.5 points in the Knee Society score, 9.3 points in the Turba score, and 49.0 points in the Kujala score. Mean level of persisting pain was 2.2. In the SF-36 score patients achieved 36.3 points physical and 51.7 points mental. The overall survival for isolated tibial insert exchange revealed 72.2 % survival at 6.25 years follow-up with a repeat revision rate of 11 %. CONCLUSIONS: Isolated tibial polyethylene insert exchange revealed a good clinical outcome. There is a tendency for better results in comparison with the information given in literature for most of the parameters including a lower rate in repeat revision.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Knee Joint/surgery , Knee Prosthesis , Polyethylene/classification , Polyethylene/therapeutic use , Adult , Aged , Aged, 80 and over , Bone Cements , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain/surgery , Pain Measurement , Physical Examination , Quality of Life , Reoperation , Retrospective Studies , Survival Analysis , Tibia/surgery , Treatment Outcome
15.
PLoS Biol ; 12(11): e1002005, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25423365

ABSTRACT

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.


Subject(s)
Arthropods/genetics , Genome , Synteny , Animals , Circadian Rhythm Signaling Peptides and Proteins/genetics , DNA Methylation , Evolution, Molecular , Female , Genome, Mitochondrial , Hormones/genetics , Male , Multigene Family , Phylogeny , Polymorphism, Genetic , Protein Kinases/genetics , RNA, Untranslated/genetics , Receptors, Odorant/genetics , Selenoproteins/genetics , Sex Chromosomes , Transcription Factors/genetics
16.
Science ; 344(6188): 1168-1173, 2014 Jun 06.
Article in English | MEDLINE | ID: mdl-24904168

ABSTRACT

Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.


Subject(s)
Lipid Metabolism/physiology , Rumen/physiology , Sheep, Domestic/genetics , Sheep, Domestic/metabolism , Amino Acid Sequence , Animals , Fatty Acids, Volatile/metabolism , Fatty Acids, Volatile/physiology , Gene Expression Regulation , Genome , Keratins, Hair-Specific/genetics , Lipid Metabolism/genetics , Molecular Sequence Data , Phylogeny , Rumen/metabolism , Sheep, Domestic/classification , Transcriptome , Wool/growth & development
17.
PLoS One ; 9(5): e97575, 2014.
Article in English | MEDLINE | ID: mdl-24840503

ABSTRACT

PURPOSE: Delays in antimicrobial therapy increase mortality in ventilator-associated pneumonia (VAP). The more objective ventilator-associated complications (VAC) are increasingly used for quality reporting. It is unknown if delays in antimicrobial administration, after patients meet VAC criteria, leads to worse outcomes. MATERIALS AND METHODS: Cohort of 81 episodes of antimicrobial treatment for VAP. We compared mortality, superinfections and treatment failures conditional on the timing of identification of VAC. RESULTS: 60% of patients with VAC had an identifiable episode at least 48 before the initiation of antimicrobials. Antimicrobial administration after the identification of VAC was not associated with intensive care unit (ICU) mortality (OR 0.71, 95% CI 0.11-4.48, p = 0.701) compared to immediate antimicrobial administration. Similarly, the risk of treatment failure or superinfection was not affected by the timing of administration of antimicrobials in VAC (HR 0.95, 95% CI 0.42-2.19, p = 0.914). CONCLUSIONS: We observed no signal of harm associated with the timing to initiate antimicrobials after the identification of a VAC. The identification of VAC should not lead clinicians to start antimicrobials before a diagnosis of VAP can be established.


Subject(s)
Pneumonia, Ventilator-Associated/drug therapy , Adult , Aged , Aged, 80 and over , Anti-Infective Agents/therapeutic use , Cohort Studies , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Time Factors
18.
Nature ; 508(7497): 494-9, 2014 Apr 24.
Article in English | MEDLINE | ID: mdl-24759411

ABSTRACT

The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner's syndrome and in phenotypic differences between the sexes in health and disease.


Subject(s)
Evolution, Molecular , Gene Dosage/genetics , Mammals/genetics , Y Chromosome/genetics , Animals , Chromosomes, Human, X/genetics , Chromosomes, Human, Y/genetics , Disease , Female , Gene Expression Regulation , Health , Humans , Male , Marsupialia/genetics , Molecular Sequence Annotation , Molecular Sequence Data , Protein Biosynthesis/genetics , Protein Stability , Selection, Genetic/genetics , Sequence Homology , Sex Characteristics , Spermatogenesis/genetics , Testis/metabolism , Transcription, Genetic/genetics , Turner Syndrome/genetics , X Chromosome/genetics
19.
BMC Genomics ; 15: 86, 2014 Jan 30.
Article in English | MEDLINE | ID: mdl-24479613

ABSTRACT

BACKGROUND: The first generation of genome sequence assemblies and annotations have had a significant impact upon our understanding of the biology of the sequenced species, the phylogenetic relationships among species, the study of populations within and across species, and have informed the biology of humans. As only a few Metazoan genomes are approaching finished quality (human, mouse, fly and worm), there is room for improvement of most genome assemblies. The honey bee (Apis mellifera) genome, published in 2006, was noted for its bimodal GC content distribution that affected the quality of the assembly in some regions and for fewer genes in the initial gene set (OGSv1.0) compared to what would be expected based on other sequenced insect genomes. RESULTS: Here, we report an improved honey bee genome assembly (Amel_4.5) with a new gene annotation set (OGSv3.2), and show that the honey bee genome contains a number of genes similar to that of other insect genomes, contrary to what was suggested in OGSv1.0. The new genome assembly is more contiguous and complete and the new gene set includes ~5000 more protein-coding genes, 50% more than previously reported. About 1/6 of the additional genes were due to improvements to the assembly, and the remaining were inferred based on new RNAseq and protein data. CONCLUSIONS: Lessons learned from this genome upgrade have important implications for future genome sequencing projects. Furthermore, the improvements significantly enhance genomic resources for the honey bee, a key model for social behavior and essential to global ecology through pollination.


Subject(s)
Bees/genetics , Genes, Insect , Animals , Base Composition , Databases, Genetic , Interspersed Repetitive Sequences/genetics , Molecular Sequence Annotation , Open Reading Frames/genetics , Peptides/analysis , Sequence Analysis, RNA , Sequence Homology, Amino Acid
20.
BMJ Qual Saf ; 22(6): 516-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23293120

ABSTRACT

This paper adopts methods from the organisational team training literature to outline how health professions education can improve patient safety. We argue that health educators can improve training quality by intentionally encouraging errors during simulation-based team training. Preventable medical errors are inevitable, but encouraging errors in low-risk settings like simulation can allow teams to have better emotional control and foresight to manage the situation if it occurs again with live patients. Our paper outlines an innovative approach for delivering team training.


Subject(s)
Administrative Personnel/education , Medical Errors/prevention & control , Patient Care Team , Safety Management , Transfer, Psychology , Administrative Personnel/psychology , Behavior Control , Humans , Organizational Innovation , Patient Simulation , Systems Integration
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