Socioeconomic inequalities and the equity impact of population-level interventions for adolescent health: an overview of systematic reviews.

OBJECTIVES: Despite robust evidence on health inequalities in adulthood, less attention has been paid to inequalities in adolescence. The aim of this overview was to examine systematic review (SR) evidence on the equity impact of population-level interventions intended to improve health, happiness and wellbeing for adolescents. STUDY DESIGN: An overview (review of systematic reviews). METHODS: Eleven electronic databases were systematically searched to identify SRs of population-level interventions for adolescent health. A secondary data analysis of socioeconomic inequality was conducted to identify whether SRs reported on primary studies in terms of disadvantage, by measures of socioeconomic status (SES) and by differential effects. RESULTS: 35,310 review titles were screened; 566 full texts were retrieved and 140 SRs met the predefined selection criteria. Differential intervention effects were considered in 42/140 (30%) SRs, 18/140 (13%) reported primary studies using an SES measure and 16/140 (11%) explicitly reported differential effects. 15/140 SRs (11%) explicitly focused on socioeconomic inequalities; of these 4/15 reported differential intervention effects in more detail, 7/15 concluded there was insufficient primary evidence to identify the impact of interventions on socioeconomic inequalities and 4/15 planned to examine differential effects by SES, but this was not reported further. CONCLUSIONS: Our overview identifies that there is limited SR evidence on the equity impact of population-level interventions for adolescent health. Strengthening the evidence on whether interventions narrow or widen inequalities for adolescents must be a priority for public health research.

Contrasting arsenic cycling in strongly and weakly stratified contaminated lakes: Evidence for temperature control on sediment-water arsenic fluxes.

Arsenic contamination of lakebed sediments is widespread due to a range of human activities, including herbicide application, waste disposal, mining, and smelter operations. The threat to aquatic ecosystems and human health is dependent on the degree of mobilization from sediments into overlying water columns and exposure of aquatic organisms. We undertook a mechanistic investigation of arsenic cycling in two impacted lakes within the Puget Sound region, a shallow weakly-stratified lake and a deep seasonally-stratified lake, with similar levels of lakebed arsenic contamination. We found that the processes that cycle arsenic between sediments and the water column differed greatly in shallow and deep lakes. In the shallow lake, seasonal temperature increases at the lakebed surface resulted in high porewater arsenic concentrations that drove larger diffusive fluxes of arsenic across the sediment-water interface compared to the deep, stratified lake where the lakebed remained ~10#x00B0;C cooler. Plankton in the shallow lake accumulated up to an order of magnitude more arsenic than plankton in the deep lake due to elevated aqueous arsenic concentrations in oxygenated waters and low phosphate: arsenate ratios in the shallow lake. As a result, strong arsenic mobilization from sediments in the shallow lake was countered by large arsenic sedimentation rates out of the water column driven by plankton settling.

Characterization of the Trehalose Utilization Operon in Streptococcus mutans Reveals that the TreR Transcriptional Regulator Is Involved in Stress Response Pathways and Toxin Production.

Streptococcus mutans, the organism most frequently associated with the development of dental caries, is able to utilize a diverse array of carbohydrates for energy metabolism. One such molecule is trehalose, a disaccharide common in human foods, which has been recently implicated in enhancing the virulence of epidemic strains of the pathogen Clostridium difficile In this study, mutants with deletions of all three genes in the putative S. mutans trehalose utilization operon were characterized, and the genes were shown to be required for wild-type levels of growth when trehalose was the only carbohydrate source provided. Interestingly, the TreR transcriptional regulator appeared to be critical for responding to oxidative stress and for mounting a protective stress tolerance response following growth at moderately acidic pH. mRNA sequencing (RNA-seq) of a treR deletion mutant suggested that in S. mutans, TreR acts as a trehalose-sensing activator of transcription of the tre operon, rather than as a repressor, as described in other species. In addition, deletion of treR caused the downregulation of a number of genes involved in genetic competence and bacteriocin production, supporting the results of a recent study linking trehalose and the S. mutans competence pathways. Finally, deletion of treR compromised the ability of S. mutans to inhibit the growth of the competing species Streptococcus gordonii and Lactococcus lactis Taking the results together, this study solidifies the role of the S. mutans tre operon in trehalose utilization and suggests novel functions for the TreR regulator, including roles in the stress response and competitive fitness.IMPORTANCES. mutans is the primary etiologic agent of dental caries, which globally is the most common chronic disease. S. mutans must be able to outcompete commensal organisms in its dental plaque niche in order to establish persistence and pathogenesis. To that end, S. mutans metabolizes a diverse array of carbohydrates to generate acid and impede its acid-sensitive neighbors. Additionally, S. mutans utilizes quorum signaling through genetic competence-associated pathways to induce production of toxins to kill its rivals. This study definitively shows that the S. mutans trehalose utilization operon is required for growth in trehalose. Furthermore, this study suggests that the S. mutans TreR transcriptional regulator has a novel role in virulence through regulation of genes involved in genetic competence and toxin production.

Moving mobile: using an open-sourced framework to enable a web-based health application on touch devices.

Computer devices using touch-enabled technology are becoming more prevalent today. The application of a touch screen high definition surgical monitor could allow not only high definition video from an endoscopic camera to be displayed, but also the display and interaction with relevant patient and health related data. However, this technology has not been quickly embraced by all health care organizations. Although traditional keyboard or mouse-based software programs may function flawlessly on a touch-based device, many are not practical due to the usage of small buttons, fonts and very complex menu systems. This paper describes an approach taken to overcome these problems. A real case study was used to demonstrate the novelty and efficiency of the proposed method.

Surgical management of pharyngocutaneous fistula after total laryngectomy.

PURPOSE: The increased use of radiation in the primary management of laryngeal carcinoma has resulted in an increase in pharyngocutaneous fistula (PCF) formation after salvage laryngectomy. The impact of this practice on surgical management strategies has been analyzed. METHODS: A retrospective review of 177 patients treated by total laryngectomy for laryngeal or hypopharyngeal squamous cell carcinoma was performed. PCF formation was documented and management strategies were analyzed. RESULTS: Preoperative radiation therapy (XRT) was administered to 86 patients (48.6%). Postoperative PCF developed in 47 patients (26.5%), including 30 (34.9%) who had received preoperative XRT versus 17 (18.6%) who had not received XRT (P = 0.015). Spontaneous PCF closure occurred in 23 patients (48.9%). Two patients died with persistent, untreated PCF. Surgical closure of PCF was performed in 22 patients (46.8%), including 17 who had received preoperative radiation (77.3%). Reconstructive methods included 9 local flaps, 17 pectoralis major (PM) flaps, and 2 free jejunal flaps. Seven of the 9 (77.8%) patients treated with local flaps had received XRT. Three patients had successful fistula closure including 2 who had not received radiation. Six of 9 patients (66.7%) developed recurrent fistulization after local flap closure necessitating PM flap closure. Overall, 14 patients (82.4%) had received preoperative XRT prior to PM flap closure. Six patients (35.3%) who had received XRT developed recurrent fistulization and 5 of these fistulas eventually closed with local wound care. The remaining patient succumbed to a carotid artery rupture. Two patients required a completion pharyngectomy and free jejunal flap reconstruction. PM flaps were used in both cases to provide soft-tissue coverage. CONCLUSIONS: Preoperative XRT increases the risk of PCF after laryngectomy and the need for surgical closure. Local flap closure has a limited role in the surgical management of PCF. PM flap reconstruction has a high complication rate including recurrent fistulization in the setting of preoperative radiation.

Thyroid storm presenting with coma.

Thyroid storm is a rare manifestation of severe thyrotoxicosis, and presentation with coma is highly atypical. A 32-year-old woman, previously euthyroid, presented in a comatose state with tachycardia, hypertension and pyrexia. The patient's trachea was intubated in the community and she was subsequently admitted to the intensive care unit with a working diagnosis of meningoencephalitis. Although hypertension was present initially, subsequent hypotension necessitated a noradrenaline infusion. The patient remained persistently tachycardic and pyrexial. Initial laboratory investigations, including examination of cerebrospinal fluid, did not identify a specific diagnosis. Subsequently, raised thyroxine and triiodothyronine levels alongside undetectable thyroid-stimulating hormone confirmed the diagnosis of thyroid storm. Following treatment for thyrotoxicosis, the patient made a full recovery and was discharged from the intensive care unit after three days. This case highlights the importance of considering thyroid disease in critically ill patients presenting with non-specific symptoms.

Identification of shared antigenic determinants of the putative human T lymphocyte antigen receptor.

A mouse antiserum, anti-gp40,49 was obtained by immunizing BALB/c mice with the putative T cell antigen receptor isolated from HPB-MLT cells. This antiserum reacted with peripheral blood lymphocyte (PBL) and a panel of immunocompetent T cell lines and clones in each case precipitating from lysates of cells labeled by surface iodination, a disulfide-linked dimer consisting of an alpha subunit Mr (46,000-49,000) and a beta subunit Mr (40,000-45,000). Variability in Mr of the two subunits, particularly of the beta (light) subunit, was observed when the receptors of immunocompetent T cell lines with different antigen specificities were compared. Anti-gp40,49 serum reacted selectively with the alpha subunit after reduction and alkylation of the protein complex. These results confirm the relationship between the gp40,49 protein complex of HPB-MLT cells and the putative T cell antigen receptor on normal immunocompetent T cells and indicate that the alpha subunit of the human receptor expressed shared determinant(s) that are immunogenic in the mouse. Some features of the T cell antigen receptor appear to be unusual in that even with a xenoantiserum against the purified molecule, only antibodies against clonotypic determinants could be detected at the cell surface by quantitative immunofluorescence analysis.

Characterization of a third form of the human T cell receptor gamma/delta.

A subpopulation of the CD3+ peripheral T lymphocytes express the TCR-gamma/delta complex. Three distinct TCR-gamma forms that differ in size and in the ability to form a disulfide bridge with the TCR-delta subunit have been described. In this study we analyze the structural difference between the non-disulfide-linked 55-kD and 40-kD TCR-gamma chains. The 40-kD TCR-gamma form contains a smaller polypeptide backbone and carries less carbohydrate compared with the 55-kD TCR-gamma form. A cDNA clone corresponding to the 40-kD TCR-gamma subunit lacks one copy of the second exon of the constant region that is present in the other TCR-gamma subunit. This exon copy encodes part of the connector region that is located between the constant domain and the membrane spanning region. We show that the number of potential N-linked glycan attachment sites are the same for the two TCR-gamma forms. Since these attachment sites are located in the connector region we conclude that the connector region influences the amount of N-linked carbohydrates added to the core TCR-gamma polypeptide, probably by affecting the conformation of the protein. In contrast to the TCR-beta constant region usage, the TCR-gamma constant regions are unequally expressed. Virtually exclusive usage of disulfide-linked complexes were found in some individuals, while both the disulfide-linked and the 40-kD, non-disulfide-linked TCR-gamma forms were detected in other subjects. The ability to distinguish these TCR-gamma/delta forms now makes it possible to study the mechanisms that govern their selection and to determine if they correspond to functionally distinct isotypes.

The pectoralis major myocutaneous flap revisited: a reliable technique for head and neck reconstruction.

The pectoralis major myocutaneous flap (PMMF) remains a useful flap for head and neck reconstruction. Although free-tissue transfer is often preferred, the benefits of the PMMF should not be overlooked. A retrospective chart review was performed on all PMMFs used at Emory for head and neck reconstruction from 1992 through 2008. A total of 139 PMMF were performed in 136 patients with an average age of 65 years. Eighty-six patients were males. All patients except one had a history of Head and Neck Cancer. A smoking history was present in 92% of the patients. Defect location included oral cavity (n = 59), pharyngeal/fistulae (n = 48), temporal bone and cheek (n = 24), oropharyngeal (n = 4), and esophageal (n = 2). The PMMF was used in 4 occasions as a salvage procedure. The survival of the flap was 99.2% (138/139). The PMMF provided definitive closure of the defect in 100% of the cases. The overall average follow-up was 10.5 months. Eighteen patients (13%) developed complications after the procedure. Patients who had radiation therapy had significantly higher complication rates. The PMMF flap remains a very versatile technique with proven reliability for soft tissue coverage of many head and neck defects.

Insights Obtained by Culturing Saccharibacteria With Their Bacterial Hosts.

Oral microbiome research has moved from asking "Who's there?" to "What are they doing?" Understanding what microbes "do" involves multiple approaches, including obtaining genomic information and examining the interspecies interactions. Recently we isolated a human oral Saccharibacteria (TM7) bacterium, HMT-952, strain TM7x, which is an ultrasmall parasite of the oral bacterium Actinomyces odontolyticus. The host-parasite interactions, such as phage-bacterium or Saccharibacteria-host bacterium, are understudied areas with large potential for insight. The Saccharibacteria phylum is a member of Candidate Phyla Radiation, a large lineage previously devoid of cultivated members. However, expanding our understanding of Saccharibacteria-host interactions requires examining multiple phylogenetically distinct Saccharibacteria-host pairs. Here we report the isolation of 3 additional Saccharibacteria species from the human oral cavity in binary coculture with their bacterial hosts. They were obtained by filtering ultrasmall Saccharibacteria cells free of other larger bacteria and inoculating them into cultures of potential host bacteria. The binary cocultures obtained could be stably passaged and studied. Complete closed genomes were obtained and allowed full genome analyses. All have small genomes (<1 Mb) characteristic of parasitic species and dramatically limited de novo synthetic pathway capabilities but include either restriction modification or CRISPR-Cas systems as part of an innate defense against foreign DNA. High levels of gene synteny exist among Saccharibacteria species. Having isolates growing in coculture with their hosts allowed time course studies of growth and parasite-host interactions by phase contrast, fluorescence in situ hybridization, and scanning electron microscopy. The cells of the 4 oral Saccharibacteria species are ultrasmall and could be seen attached to their larger Actinobacteria hosts. Parasite attachment appears to lead to host cell death and lysis. The successful cultivation of Saccharibacteria species has significantly expanded our understanding of these ultrasmall Candidate Phyla Radiation bacteria.

Calcineurin inhibition eliminates the normal inverted U curve, enhances acquisition and prolongs memory in a mammalian 3'-5'-cyclic AMP-dependent learning paradigm.

The role protein phosphatase 2B (calcineurin, CaN) plays in learning and memory has received a significant amount of attention due to its promotion of the dephosphorylation of 3'-5'-cyclic AMP response element binding protein (CREB). Researchers have ascertained that overexpression of CaN is associated with memory retention deficits [Foster TC, Sharrow KM, Masse JR, Norris CM, Kumar A (2001) Calcineurin links Ca(2+) dysregulation with brain aging. J Neurosci 21:4066-4073; Mansuy IM, Mayford M, Jacob B, Kandel ER, Bach ME (1998) Restricted and regulated overexpression reveals calcineurin as a key component in the transition from short-term to long-term memory. Cell 92:39-49], while CaN inhibition enhances learning and memory [Gerdjikov TV, Beninger RJ (2005) Differential effects of calcineurin inhibition and protein kinase A activation on nucleus accumbens amphetamine-produced conditioned place preference in rats. Eur J Neurosci 22:697-705; Ikegami S, Inokuchi K (2000) Antisense DNA against calcineurin facilitates memory in contextual fear conditioning by lowering the threshold for hippocampal long-term potentiation induction. Neuroscience 98:637-646]. The present study hypothesized that infusion of a CaN inhibitor (FK506) bilaterally into the olfactory bulbs of postnatal day 6 Sprague Dawley rat pups would prolong the duration of a conditioned odor preference and retard cyclic AMP response element binding protein dephosphorylation. A 2 mg/kg s.c. injection of isoproterenol (ISO, beta-adrenoceptor agonist) was paired with a 10 min exposure to peppermint and subsequently an infusion of FK506. Immunohistochemistry for phosphorylated 3'-5'-cyclic AMP response element binding protein (pCREB) revealed that unilateral infusion of FK506 resulted in an amplification of phosphorylated CREB in the olfactory bulb 40 min after training compared with saline-infused bulbs. Pups infused bilaterally with FK506 maintained a learned preference for peppermint 48, 72 and 96 h after training. CaN inhibition also modified the conventional inverted U curve obtained when ISO is used to replace stroking, as the unconditioned stimulus. When pups were infused with FK506, learning occurred with sub- and supra-optimal doses of ISO indicating that CaN overcomes non-optimal effects ISO may have on learning. We demonstrate that CaN inhibition can extend the duration of conditioned olfactory memory and may provide a target for memory prolongation that is superior to even phosphodiesterase inhibition observed in previous studies.

Immunochemical proof that a novel rearranging gene encodes the T cell receptor delta subunit.

The T cell receptor (TCR) delta protein is expressed as part of a heterodimer with TCR gamma, in association with the CD3 polypeptides on a subset of functional peripheral blood T lymphocytes, thymocytes, and certain leukemic T cell lines. A monoclonal antibody directed against TCR delta was produced that binds specifically to the surface of several TCR gamma delta cell lines and immunoprecipitates the TCR gamma delta as a heterodimer from Triton X-100 detergent lysates and also immunoprecipitates the TCR delta subunit alone after chain separation. A candidate human TCR delta complementary DNA clone (IDP2 O-240/38), reported in a companion paper, was isolated by the subtractive library approach from a TCR gamma delta cell line. This complementary DNA clone was used to direct the synthesis of a polypeptide that is specifically recognized by the monoclonal antibody to TCR delta. This complementary DNA clone thus corresponds to the gene that encodes the TCR delta subunit.

Structurally divergent human T cell receptor gamma proteins encoded by distinct C gamma genes.

The human T cell receptor (TCR) gamma polypeptide occurs in structurally distinct forms on certain peripheral blood T lymphocytes. Complementary DNA clones representing the transcripts of functionally rearranged TCR gamma genes in these cells have been analyzed. The expression of a disulfide-linked and a nondisulfide-linked form of TCR gamma correlates with the use of the C gamma 1 and C gamma 2 constant-region gene segments, respectively. Variability in TCR gamma polypeptide size and disulfide linkage is determined by the number of copies and the sequence of a repeated segment of the constant region. Thus C gamma 1 and C gamma 2 are used to generate structurally distinct, yet functional, T3-associated receptor complexes on peripheral blood lymphocytes. Tryptic peptide mapping suggests that the T3-associated TCR gamma and delta peptides in the nondisulfide-linked form are distinct.

Gnathotrichus sulcatus: synergistic response to enantiomers of the aggregation pheromone sulcatol.

In laboratory and field bioassays, Gnathotrichus sulcatus responded to sulcatol (6-methyl-5-hepten-2-ol) only when both enantiomers were present. Response was greater to racemic sulcatol than to a mixture (65 : 35) of S-(+) and R-(-) enantiomers, the naturally occurring isomeric ratio. Enantiomer-specific active sites on receptor proteins in the same or different cells are implicated.

Extensive junctional diversity of rearranged human T cell receptor delta genes.

The human T cell receptor delta (TCR delta) gene encodes one component of the TCR gamma delta-CD3 complex found on subsets of peripheral blood and thymic T cells. Human TCR delta diversity was estimated by characterizing rearrangements in TCR gamma delta cell lines and determining the structures of complementary DNA clones representing functional and nonfunctional transcripts in these cell lines. One V delta segment and one J delta segment were identified in all functional transcripts, although a distinct J delta segment was identified in a truncated transcript. Further, one D delta element was identified, and evidence for the use of an additional D delta element was obtained. Thus human TCR delta genes appear to use a limited number of germline elements. However, the apparent use of two D delta elements in tandem coupled with imprecise joining and extensive incorporation of N nucleotides generates unprecedented variability in the junctional region.

Copper and cadmium: responses in Pseudomonas putida KT2440.

AIMS: To compare responses of a soil bacterium to Cu and Cd. METHODS AND RESULTS: In minimal medium, Cd caused a dose-dependent growth stasis of logarithmic phase cells of Pseudomonas putida, strain KT2440, whereas Cu did not compromise growth up to 10 mg l(-1). Proteomics showed changes in accumulation of both membrane and soluble proteins by 6 h of treatment; increased Krebs cycle enzymes were apparent. Transcript analysis showed Cd- and Cu-induced different genes. Cd-induced genes encoding the transcriptional regulator CzrR2; an outer membrane protein associated with lipopolysaccharide stability, H1; two oxidative stress protective proteins and the P-type ATPase, CadA2, associated with Cd(2+) efflux. The genes most responsive to Cu encoded the regulator CopR1 and the outer membrane resistance protein regulated by CopR1, CopB1; a putative porin, PorD and the Cu-binding protein, PacZ or CopZ, and CopA2. CONCLUSIONS: These findings support that a soil pseudomonad restricts internalization of the metals by using different sets of binding proteins and efflux pumps. Activation of mechanisms to protect against oxidative stress also was evident especially with Cd exposure. SIGNIFICANCE AND IMPACT OF THE STUDY: The differential cellular responses to Cd and Cu suggest that risk assessment for Cd and Cu should be different.

Saccharibacteria (TM7) in the Human Oral Microbiome.

Bacteria from the Saccharibacteria phylum (formerly known as TM7) are ubiquitous members of the human oral microbiome and are part of the Candidate Phyla Radiation. Recent studies have revealed remarkable 16S rRNA diversity in environmental and mammalian host-associated members across this phylum, and their association with oral mucosal infectious diseases has been reported. However, due to their recalcitrance to conventional cultivation, TM7's physiology, lifestyle, and role in health and diseases remain elusive. The recent cultivation and characterization of Nanosynbacter lyticus type strain TM7x (HMT_952)-the first Saccharibacteria strain coisolated as an ultrasmall obligate parasite with its bacterial host from the human oral cavity-provide a rare glimpse into the novel symbiotic lifestyle of these enigmatic human-associated bacteria. TM7x is unique among all bacteria: it has an ultrasmall size and lives on the surface of its host bacterium. With a highly reduced genome, it lacks the ability to synthesize any of its own amino acids, vitamins, or cell wall precursors and must parasitize other oral bacteria. TM7x displays a highly dynamic interaction with its bacterial hosts, as reflected by the reciprocal morphologic and physiologic changes in both partners. Furthermore, depending on environmental conditions, TM7x can exhibit virulent killing of its host bacterium. Thus, Saccharibacteria potentially affect oral microbial ecology by modulating the oral microbiome structure hierarchy and functionality through affecting the bacterial host's physiology, inhibiting the host's growth dynamics, or affecting the relative abundance of the host via direct killing. At this time, several other uncharacterized members of this phylum have been detected in various human body sites at high prevalence. In the oral cavity alone, at least 6 distinct groups vary widely in relative abundance across anatomic sites. Here, we review the current knowledge on the diversity and unique biology of this recently uncovered group of ultrasmall bacteria.

Development of a microwave stunning system for cattle 2: Preliminary observations on behavioural responses and EEG.

DTS: Diathermic Syncope® (DTS) is a novel system for rendering animals insensible prior to slaughter, utilizing microwave energy to induce a rise in temperature in the brain to a point at which the animal is expected to lose consciousness. During development and optimisation of the system, two trials were carried out utilizing non-anaesthetized adult cattle, to gather data on behavioural outcomes and EEG changes following energy application. In trial1, ten cattle received DTS treatments (high energy >290 kJ, n = 3; low energy <200 kJ, n = 4; and intermediate 200 < 290 kJ, n = 3), and seven received captive bolt stunning, prior to exsanguination. In trial 2, following improvements to the efficiency of energy delivery, 20 cattle received DTS (200-360 kJ). Post treatment EEG was characterized by seizure-like activity and reductions in 95% spectral edge and median frequencies; with EEG suppression persisting for at least 80 s up to over 4 min post treatment application. Animals showed: Loss of posture, Loss of corneal responses; Loss of withdrawal response (pinprick); Eye staring, not following movement. The animals remained unresponsive to stimuli for up to 4 min post DTS, and behavioural expression of distress was not observed. Seventeen of the 30 animals showed indications of returning reflex responses after 100 s post treatment, suggesting that animals receiving lower energy applications may recover from the stun.

Oxygen-dependent autoaggregation in Shewanella oneidensis MR-1.

In aerobic chemostat cultures maintained at 50% dissolved O(2) tension (3.5 mg l(-1) dissolved O(2)), Shewanella oneidensis strain MR-1 rapidly aggregated upon addition of 0.68 mM CaCl(2) and retained this multicellular phenotype at high dilution rates. Confocal microscopy analysis of the extracellular matrix material contributing to the stability of the aggregate structures revealed the presence of extracellular DNA, protein and glycoconjugates. Upon onset of O(2)-limited growth (dissolved O(2) below detection) however, the Ca(2+)-supplemented chemostat cultures of strain MR-1 rapidly disaggregated and grew as motile dispersed cells. Global transcriptome analysis comparing aerobic aggregated to O(2)-limited unaggregated cells identified genes encoding cell-to-cell and cell-to-surface adhesion factors whose transcription increased upon exposure to increased O(2) concentrations. The aerobic aggregated cells also revealed increased expression of putative anaerobic electron transfer and homologues of metal reduction genes, including mtrD (SO1782), mtrE (SO1781) and mtrF (SO1780). Our data indicate that mechanisms involved in autoaggregation of MR-1 are dependent on the function of pilD gene which encodes a putative prepilin peptidase. Mutants of S. oneidensis strain MR-1 deficient in PilD and associated pathways, including type IV and Msh pili biogenesis, displayed a moderate increase in sensitivity to H(2)O(2). Taken together, our evidence indicates that aggregate formation in S. oneidensis MR-1 may serve as an alternative or an addition to biochemical detoxification to reduce the oxidative stress associated with production of reactive oxygen species during aerobic metabolism while facilitating the development of hypoxic conditions within the aggregate interior.