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The methoxy- and fluoro-derivatives of meta-nitrophenylacetic acid (mNPA) chromophores undergo photodecarboxylation with comparable quantum yields to unsubstituted mNPA, but uncage at red-shifted excitation wavelengths. This observation prompted us to investigate DPAdeCageOMe (2-[bis(pyridin-2-ylmethyl)amino]-2-(4-methoxy-3-nitrophenyl)acetic acid) and DPAdeCageF (2-[bis(pyridin-2-ylmethyl)amino]-2-(4-fluoro-3-nitrophenyl)acetic acid) as Zn2+ photocages. DPAdeCageOMe has a high quantum yield and exhibits other photophysical properties comparable to XDPAdeCage ({bis[(2-pyridyl)methyl]amino}(9-oxo-2-xanthenyl) acetic acid), the best perforiming Zn2+ photocage reported to date. Since the synthesis of DPAdeCageOMe is more straightforward than XDPACage, the new photocage will be a highly competitive tool for biological applications.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by responsiveness to chemotherapy and differentiating agents [1]. The current standard of care for the ...

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination therapy yields high complete remission and disease-free survival rates in acute promyelocytic leukemia (APL). ATO is dosed on actual body weight and high ATO doses in overweight patients may contribute to increased toxicity. We performed a retrospective, two-center study comparing toxicities in patients who received the Lo-Coco et al ATRA/ATO regimen with capped ATO, ≤10 mg/dose, and non-capped ATO, >10 mg/dose. A total of 44 patients were included; 15 received doses ≤10 mg and 29 received >10 mg. During induction, there was no difference in the incidence of grade ≥3 hepatotoxicity, grade ≥3 QTc prolongation, neurotoxicity, and cardiac toxicity between groups. In consolidation, patients receiving >10 mg/dose experienced a greater incidence of neurotoxicity (66.7% vs 22.2%; p = 0.046). Capping doses saved $24634.37/patient and reduced waste of partially-used vials. At a median follow-up of 27 months, no disease relapses occurred in either group. This represents an opportunity to improve the safety profile of this highly effective regimen.

Summary: Individuals with kidney disease have a high prevalence of chronic noncancer pain. Although opioids are not a recommended treatment option for chronic noncancer pain in the general population, a higher percentage of individuals with kidney disease receive opioid prescriptions for chronic pain. Individuals with kidney disease have an increased risk for opioid adverse events because of changes related to kidney disease progression, normative aging, and the pharmacology of opioid medications. Despite the frequent prescription of opioids for chronic noncancer pain among those with kidney disease, there are no guidelines for opioid management in this population. This article reviews the pharmacologic challenges of opioid use in relation to the physiologic changes occurring in kidney disease and normative aging. We highlight how understanding opioid pharmacology and human physiology can support safe practices of opioid management in patients with kidney disease who require opioids for chronic noncancer pain.

Introduction Patients with sickle cell disease (SCD) commonly experience negative attitudes from health care providers, leading to significant barriers to care and management of pain (Haywood 2009). Incidence of SCD is high on the South Side of Chicago and the University of Chicago Medical Center (UCMC) is among the primary systems in the area caring for these patients. Based on the results of a small pilot study conducted at UCMC in 2019, providers can hold biased beliefs that lead to inadequate delivery of analgesia (Nelson 2019). Because internal medicine (IM) and emergency medicine (EM) residents are often at the frontline of caring for patients with SCD, we sought to explore attitudes and beliefs amongst IM and EM residents at our institution in order to address biases with future interventions. Methods We conducted anonymous surveys using validated questions (Haywood 2011) for UCMC IM and EM residents. The surveys were administered in paper form during conferences in July 2019 to IM and EM residents and January 2020 to IM residents. The surveys, which included questions that assess barriers to care of patients with SCD and attitudes amongst providers, utilize the 4-point Likert scale in which higher scores correspond to stronger agreement with the statement. Participants were asked to provide non-identifiable demographic information including sex, ethnicity, age range, training year (PGY-1- PGY-3), and residency program. Responses were pooled and analyzed to assess for differences in attitudes by residency program (EM vs. IM), sex, age, year of training, and ethnicity. Statistical analysis was performed using the student's t-tests to identify differences in average responses and ANOVA to examine for confounding variables. Results Sixty-six residents were included in this study: 44 IM and 22 EM. Residents were 41% female and 58% male, ranging in age from 20-39 (median 25-29 yrs). Forty-eight percent of residents were White, 20% Asian/Asian American, 11% Black/African American, 9% Latinx, and 12% unidentified/other. Resident training level included 20% PGY-1 (13), 53% PGY-2 (35), and 29% PGY-3 (19). In terms of attitudes, 38% of IM and EM residents overall believed that patients with SCD over-report pain and are "drug-seeking" (N=66). IM residents (84% N=44) were more likely to consider patients to be frustrating to work with compared to EM residents (23% N=22, p When comparing these responses by year of training, attitudes generally became more negative with increased training, with advanced residents more likely to believe that SCD patients over-report pain (p=0.011), feel more frustrated caring for patients (p Considering barriers to SCD pain management, 100% of IM residents (N=23) believed opioid tolerance was a significant barrier, followed by 92% reporting opioid dependence, 83% side effects, 79% addiction, and 67% regulatory oversight. Conclusion This study highlights gaps in resident understanding of SCD and reveals biases held amongst IM and EM residents. Biases are augmented amongst IM residents and tend to become more exaggerated with increased level of training. The latter result may be confounded by burnout, which was not directly assessed in this study. The differences observed between IM and EM residents may be due to variation in education, workflow, or program diversity (although effect of ethnicity was not statistically significant). Resident-perceived barriers also seem to be focused on negative patient-centered factors (dependence, addiction, tolerance) rather than systemic limitations (availability, training, efficacy), likely reflecting negative resident attitudes as seen in previous studies (Haywood 2009). These data demonstrate an unmet need, underlining the importance of developing education, training, and potentially wellness programs to confront biases, build positive attitudes toward patients with SCD and ultimately remove barriers to care of patients with SCD. Disclosures No relevant conflicts of interest to declare.

Evidence suggests that management of food insecurity in primary care may enhance preventive care delivery. This study assessed the impact of a food pantry in a pediatric primary care center over 22 months. Quantitative outcome assessments (number of children affected, number of referrals, and completion of preventative services) compared the child receiving food from the pantry to age-matched controls. Commonalities from interviews with pantry-using families were identified using thematic analysis. A total of 504 index patients received food from the pantry during an office visit. There were 546 in-clinic and community referrals. There was no significant relationship between accessing the pantry and preventative service completion by 27 months of age. Themes that emerged during interviews included the need for an emergency food source, facilitation of referrals, and increased trust in the clinic. An in-clinic food pantry is a feasible and family-welcomed approach to address food insecurity in pediatric primary care.

BACKGROUND AND OBJECTIVES: Workflow inefficiencies by medical teams caring for hospitalized patients may affect patient care and team experience. At our institution, complexity and clinical volume of the pediatric hospital medicine (HM) service have increased over time; however, efficient workflow expectations were lacking. We aimed to increase the percentage of HM teams meeting 3 efficiency criteria (70% nurses present for rounds, rounds completed by 11:30 am, and HM attending notes completed by 5 pm) from 28% to 80% within 1 year. METHODS: Improvement efforts targeted 5 HM teams at a large academic hospital. Our multidisciplinary team, including HM attending physicians, pediatric residents, and nurses, focused on several key drivers: shared expectations, enhanced physician and nursing buy-in and communication, streamlined rounding process, and data transparency. Interventions included (1) daily rounding expectations with prerounds huddle, (2) visible reminders, (3) complex care team scheduled rounds, (4) real-time nurse notification of rounds via electronic platform, (5) workflow redesign, (6) attending feedback and data transparency, and (7) resource attending implementation. Attending physicians entered efficiency data each day through a Research Electronic Data Capture survey. Annotated control charts were used to assess the impact of interventions over time. RESULTS: Through sequential interventions, the percentage of HM teams meeting all 3 efficiency criteria increased from 28% to 61%. Nursing presence on rounds improved, and rounds end time compliance remained high, whereas attending note completion time remained variable. CONCLUSIONS: Inpatient workflow for pediatric providers was improved by setting clear expectations and enhancing team communication; competing demands while on service contributed to difficulty in improving timely attending note completion.

Public misperceptions about the pharmacy profession have the potential to impact pharmacy education, practice, and the health of those who pharmacists serve. Student misperceptions of the profession can lead to fewer applicants to pharmacy schools and frustration among pharmacy students and faculty members. With the recent decline in applicants to Doctor of Pharmacy (PharmD) programs, professional pharmacy organizations, colleges and schools of pharmacy, and individual pharmacists must implement strategies that mitigate these misperceptions. This commentary discusses the potential impact of prospective health students’ (ie, students pursuing admission to health professional programs) misperceptions on the supply of quality candidates to PharmD programs. Strategies to elevate the image of the profession at the individual and collegiate level are discussed.

* Abbreviations: app — : application FI — : food insecurity SNAP — : Supplemental Nutrition Assistance Program USDA — : US Department of Agriculture WIC — : Supplemental Nutrition Program for Women, Infants, and Children Maya is a 4-year-old girl who is presenting to our office for her well-child check. A familiar mark on her social screening questionnaire reveals that her family is worried that their food budget will run out before the end of the month. As we enter the room, we catch Maya’s mother in a yawn; she apologizes because she came straight from an overnight shift. Maya and her sister, both with juice-stained lips, are immersed in a video that is playing on their mother’s smartphone as we discuss growth charts and inhalers. Finally, we turn to Maya’s dietary history and the potential reality of food insecurity (FI). As our conversation starts, the phone rings, interrupting the video and our conversation. The family’s ride is out front, and they cannot wait. As they are rushing out the door, all we can do is provide them with a list of local food pantries. We are left dissatisfied. With recent advances in technology, how might we have more effectively and efficiently addressed this family’s FI? One in 6 American families experience FI, an inadequate access to food because of a lack of money or other resources.1 As pediatricians, we must identify and appropriately respond to FI.2 Although screening can help identify some children with FI, others may present more insidiously, with developmental delays, behavioral problems, or frequent hospitalizations, the effects of which may carry into adulthood.3 Pediatric trainees, who are often on the frontline providing primary care to at-risk families, are in a unique position to identify and respond to the needs … Address correspondence to Michelle Phan, MD, Pediatric Residency Program, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229. E-mail: michelle.phan{at}cchmc.org

Negative perceptions or underdeveloped understanding of healthcare team member roles can impact the functionality of the team and stunt innovations in interprofessional practice and education. Therefore, the intent of this study was to explore the perception of pharmacists' role on the healthcare team by future team members: prospective health professional students. The study utilised a survey to examine these perceptions in prospective health professional students (n = 34) nearing the application process to health professional school. A coding process was used to explore open-ended text responses through a line-by-line analysis and identify emerging themes regarding perception of pharmacists' roles, responsibilities, and practice settings. Quantitative data examined perception of pharmacists by intended prospective profession, healthcare experience, and pharmacy experience. Results indicate that while prospective health professional students find pharmacists to be an important part of the healthcare team, they lack a developed understanding of pharmacists' roles, responsibilities, and practice settings. Identifying and addressing prospective health professional students' misperceptions surrounding pharmacists' roles and responsibilities may encourage them to make informed career decisions and shape them into more knowledgeable future professionals with the ability to better impact patient care on interprofessional teams.

Objective: Children with Down syndrome (DS) have an increased risk of neonatal complications and comorbidities compared to the general population; however, the incidence, optimal screening intervals and outcomes in this population are uncertain. The purpose of this study is to phenotypically define this population of children with DS using a large multi-age and ethnic sample and current American Academy of Pediatrics (AAP) Guidelines testing practices. Method: This is a retrospective review of a large cohort of 1,108 children with DS (male=602; mean age at initial contact: 5.72 years, SD ± 5.51) who received care at the Sie Center for Down Syndrome (SCDS) at The Children’s Hospital Colorado from 2011 and 2016. Clinical data were collected from a prospective patient clinic database. Clinical details were collected, which included demographics, prenatal and birth history and complications, comorbidities, procedures, treatment plans and outcomes. Results: Medical complications requiring admission to the neonatal intensive care unit were identified in 70.6% of children with DS. Frequent causes for these neonatal admissions included: Required oxygen (60.7%), feeding problem (48.2%), Respiratory Distress Syndrome (21.4%) and pulmonary hypertension (14.7%). Incidence of medical comorbidities in our population with DS included cardiac defects (64.3%), abnormal sleep study (71.1%), abnormal thyroid study (29.1%), pulmonary aspiration (12.2%), celiac disease (5.0%) and pulmonary arterial hypertension (28.3%). Conclusion: Clinical data provides results from one of the largest investigations at a single pediatric hospital for children and young adults with DS in the US. This study describes the comorbidities affecting individuals with DS more accurately by applying AAP guidelines in studying a larger population than previously defined. This result improves our understanding of the incidence and identification of medical conditions in children with DS and reinforces recommendations on medical care screening for individuals with DS.

The 2,272,351–base pair genome ofNeisseria meningitidisstrain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior ofN. meningitidiscan be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally,N. meningitidiscontains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.

The common earthworm Lumbricus terrestris L. is an invasive species that was introduced to North America by European settlers. Subsequently, earthworms have been distributed by human activity, invaded a wide geographic range and changed previously earthworm-free ecosystems. In the present study we analyzed seven European and four North American populations from a wide geographic range at three formerly described nuclear microsatellite markers. All three markers produced multi-banding patterns and marker presence versus absence was scored in 88 narrow size intervals. Similar levels of genetic variation were observed for North American (Nei's gene diversity = 0.058, Shannon's I = 0.100) and European populations (Nei's gene diversity = 0.064, Shannon's I = 0.104). North American populations showed a higher similarity among each other than European populations in accordance with their recent introduction to North America. The relatively high level of genetic variation in North American populations and the high similarity among each other suggest their establishment from genetically diverse founder populations and rapid human-mediated population expansion. The source regions in Europe are still unclear from this analysis.

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.

The complete genome of the green-sulfur eubacterium Chlorobium tepidum TLS was determined to be a single circular chromosome of 2,154,946 bp. This represents the first genome sequence from the phylum Chlorobia , whose members perform anoxygenic photosynthesis by the reductive tricarboxylic acid cycle. Genome comparisons have identified genes in C. tepidum that are highly conserved among photosynthetic species. Many of these have no assigned function and may play novel roles in photosynthesis or photobiology. Phylogenomic analysis reveals likely duplications of genes involved in biosynthetic pathways for photosynthesis and the metabolism of sulfur and nitrogen as well as strong similarities between metabolic processes in C. tepidum and many Archaeal species.

We have determined that Borrelia burgdorferi strain B31 MI carries 21 extrachromosomal DNA elements, the largest number known for any bacterium. Among these are 12 linear and nine circular plasmids, whose sequences total 610 694 bp. We report here the nucleotide sequence of three linear and seven circular plasmids (comprising 290 546 bp) in this infectious isolate. This completes the genome sequencing project for this organism; its genome size is 1 521 419 bp (plus about 2000 bp of undetermined telomeric sequences). Analysis of the sequence implies that there has been extensive and sometimes rather recent DNA rearrangement among a number of the linear plasmids. Many of these events appear to have been mediated by recombinational processes that formed duplications. These many regions of similarity are reflected in the fact that most plasmid genes are members of one of the genome's 161 paralogous gene families; 107 of these gene families, which vary in size from two to 41 members, contain at least one plasmid gene. These rearrangements appear to have contributed to a surprisingly large number of apparently non-functional pseudogenes, a very unusual feature for a prokaryotic genome. The presence of these damaged genes suggests that some of the plasmids may be in a period of rapid evolution. The sequence predicts 535 plasmid genes ≥300 bp in length that may be intact and 167 apparently mutationally damaged and/or unexpressed genes (pseudogenes). The large majority, over 90%, of genes on these plasmids have no convincing similarity to genes outside Borrelia, suggesting that they perform specialized functions.

The genome of the bacterium Borrelia burgdorferi B31, the aetiologic agent of Lyme disease, contains a linear chromosome of 910,725 base pairs and at least 17 linear and circular plasmids with a combined size of more than 533,000 base pairs. The chromosome contains 853 genes encoding a basic set of proteins for DNA replication, transcription, translation, solute transport and energy metabolism, but, like Mycoplasma genitalium, it contains no genes for cellular biosynthetic reactions. Because B. burgdorferi and M. genitalium are distantly related eubacteria, we suggest that their limited metabolic capacities reflect convergent evolution by gene loss from more metabolically competent progenitors. Of 430 genes on 11 plasmids, most have no known biological function; 39% of plasmid genes are paralogues that form 47 gene families. The biological significance of the multiple plasmid-encoded genes is not clear, although they may be involved in antigenic variation or immune evasion.

Helicobacter pylori, strain 26695, has a circular genome of 1,667,867 base pairs and 1,590 predicted coding sequences. Sequence analysis indicates that H. pylori has well-developed systems for motility, for scavenging iron, and for DNA restriction and modification. Many putative adhesins, lipoproteins and other outer membrane proteins were identified, underscoring the potential complexity of host-pathogen interaction. Based on the large number of sequence-related genes encoding outer membrane proteins and the presence of homopolymeric tracts and dinucleotide repeats in coding sequences, H. pylori, like several other mucosal pathogens, probably uses recombination and slipped-strand mispairing within repeats as mechanisms for antigenic variation and adaptive evolution. Consistent with its restricted niche, H. pylori has a few regulatory networks, and a limited metabolic repertoire and biosynthetic capacity. Its survival in acid conditions depends, in part, on its ability to establish a positive inside-membrane potential in low pH.

Key Points � Down syndrome (DS), with an incidence of 1 in 691 live births, is the most common chromosomal cause of intellectual disability. � To avoid the pitfall of diagnostic overshadowing, the physician should remember that people with DS are at an increased risk for certain comorbidiites and at risk for the same illnesses that affect all children. � Frequent hearing and vision evaluations are indicated due to the high prevalence of hearing and vision abnormalities (>50%) in individuals with DS. � The risk of thyroid disease in DS is in the 20-30% range (requiring yearly thyroid labs); newly recognized comorbidities also needing screening are celiac disease and autism (both in the 7% range). � The medical care of children with DS requires vigilance regarding their predisposition to certain medical issues; however, after many years in caring for children with DS and their families, this experience provides continuing rewards.

Virulence and immunity are poorly understood inMycobacterium tuberculosis.We sequenced the complete genome of theM. tuberculosisclinical strain CDC1551 and performed a whole-genome comparison with the laboratory strain H37Rv in order to identify polymorphic sequences with potential relevance to disease pathogenesis, immunity, and evolution. We found large-sequence and single-nucleotide polymorphisms in numerous genes. Polymorphic loci included a phospholipase C, a membrane lipoprotein, members of an adenylate cyclase gene family, and members of the PE/PPE gene family, some of which have been implicated in virulence or the host immune response. Several gene families, including the PE/PPE gene family, also had significantly higher synonymous and nonsynonymous substitution frequencies compared to the genome as a whole. We tested a large sample ofM. tuberculosisclinical isolates for a subset of the large-sequence and single-nucleotide polymorphisms and found widespread genetic variability at many of these loci. We performed phylogenetic and epidemiological analysis to investigate the evolutionary relationships among isolates and the origins of specific polymorphic loci. A number of these polymorphisms appear to have occurred multiple times as independent events, suggesting that these changes may be under selective pressure. Together, these results demonstrate that polymorphisms amongM. tuberculosisstrains are more extensive than initially anticipated, and genetic variation may have an important role in disease pathogenesis and immunity.

The 2,160,837–base pair genome sequence of an isolate of Streptococcus pneumoniae , a Gram-positive pathogen that causes pneumonia, bacteremia, meningitis, and otitis media, contains 2236 predicted coding regions; of these, 1440 (64%) were assigned a biological role. Approximately 5% of the genome is composed of insertion sequences that may contribute to genome rearrangements through uptake of foreign DNA. Extracellular enzyme systems for the metabolism of polysaccharides and hexosamines provide a substantial source of carbon and nitrogen for S. pneumoniae and also damage host tissues and facilitate colonization. A motif identified within the signal peptide of proteins is potentially involved in targeting these proteins to the cell surface of low–guanine/cytosine (GC) Gram-positive species. Several surface-exposed proteins that may serve as potential vaccine candidates were identified. Comparative genome hybridization with DNA arrays revealed strain differences in S. pneumoniae that could contribute to differences in virulence and antigenicity.

The complete genome sequence of the radiation-resistant bacterium Deinococcus radiodurans R1 is composed of two chromosomes (2,648,638 and 412,348 base pairs), a megaplasmid (177,466 base pairs), and a small plasmid (45,704 base pairs), yielding a total genome of 3,284,156 base pairs. Multiple components distributed on the chromosomes and megaplasmid that contribute to the ability of D. radiodurans to survive under conditions of starvation, oxidative stress, and high amounts of DNA damage were identified. Deinococcus radiodurans represents an organism in which all systems for DNA repair, DNA damage export, desiccation and starvation recovery, and genetic redundancy are present in one cell.

The complete genome sequence of Treponema pallidum was determined and shown to be 1,138,006 base pairs containing 1041 predicted coding sequences (open reading frames). Systems for DNA replication, transcription, translation, and repair are intact, but catabolic and biosynthetic activities are minimized. The number of identifiable transporters is small, and no phosphoenolpyruvate:phosphotransferase carbohydrate transporters were found. Potential virulence factors include a family of 12 potential membrane proteins and several putative hemolysins. Comparison of the T. pallidum genome sequence with that of another pathogenic spirochete, Borrelia burgdorferi , the agent of Lyme disease, identified unique and common genes and substantiates the considerable diversity observed among pathogenic spirochetes.

Archaeoglobus fulgidus is the first sulphur-metabolizing organism to have its genome sequence determined. Its genome of 2,178,400 base pairs contains 2,436 open reading frames (ORFs). The information processing systems and the biosynthetic pathways for essential components (nucleotides, amino acids and cofactors) have extensive correlation with their counterparts in the archaeon Methanococcus jannaschii. The genomes of these two Archaea indicate dramatic differences in the way these organisms sense their environment, perform regulatory and transport functions, and gain energy. In contrast to M. jannaschii, A. fulgidus has fewer restriction-modification systems, and none of its genes appears to contain inteins. A quarter (651 ORFs) of the A. fulgidus genome encodes functionally uncharacterized yet conserved proteins, two-thirds of which are shared with M. jannaschii (428 ORFs). Another quarter of the genome encodes new proteins indicating substantial archaeal gene diversity.

The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea.

Here we determine the complete genomic sequence of the Gram negative, γ-Proteobacterium Vibrio cholerae El Tor N16961 to be 4,033,460 base pairs (bp). The genome consists of two circular chromosomes of 2,961,146 bp and 1,072,314 bp that together encode 3,885 open reading frames. The vast majority of recognizable genes for essential cell functions (such as DNA replication, transcription, translation and cell-wall biosynthesis) and pathogenicity (for example, toxins, surface antigens and adhesins) are located on the large chromosome. In contrast, the small chromosome contains a larger fraction (59%) of hypothetical genes compared with the large chromosome (42%), and also contains many more genes that appear to have origins other than the γ-Proteobacteria. The small chromosome also carries a gene capture system (the integron island) and host ‘addiction’ genes that are typically found on plasmids; thus, the small chromosome may have originally been a megaplasmid that was captured by an ancestral Vibrio species. The V. cholerae genomic sequence provides a starting point for understanding how a free-living, environmental organism emerged to become a significant human bacterial pathogen. Supplementary information The online version of this article (doi:10.1038/35020000) contains supplementary material, which is available to authorized users.