Leppäniemi A: Organization of selleck chemicals llc emergency surgery. Br J Surg 2014,101(1):e7-e8.PubMedCrossRef 5. Catena F, Sartelli M, Ansaloni L, Moore F, Moore EE: Second WSES convention, WJES impact factor, and emergency surgery worldwide. World J Emerg Surg 2013,8(1):15. doi: 10.1186/1749–7922–8-15PubMedCentralPubMedCrossRef 6. Catena F, Moore EE: Emergency surgery, acute care surgery and the boulevard of broken dreams. World J Emerg Surg 2009, 4:4.PubMedCentralPubMedCrossRef 7. Catena F, Moore EE: World Journal of Emergency Surgery (WJES), World Society of Emergency Surgery

(WSES) and the role of emergency surgery in the world. World J Emerg Surg 2007, 8:2–3.”
“Introduction The incidence and epidemiological causes of maxillofacial (MF) trauma and facial fractures varies widely in different CB-839 regions of the world due to social, economical, cultural consequences, awareness of traffic regulations and alcohol consumption. Reports from distinct regions in Turkey also have different etiological findings [1, 2]. According to the studies in developed countries assault is the leading cause of facial fractures followed mostly by motor vehicle accidents, pedestrian collisions, stumbling, sports and industrial accidents but the leading cause shifts to road traffic accidents in underdeveloped or developing areas of the world followed by assaults and other reasons including warfare [3–9]. Diagnosis and management

Screening Library price Edoxaban facial injuries are a challenge particularly in the setting of coexisting polytrauma in emergency department. Our goal is to broaden clinical data of MF trauma patients for public health measures. It is our credence that broader knowledge of MF trauma patients’ epidemiological properties and trauma patterns with simultaneous injuries in different areas of the

body may help emergency physicians to deliver more accurate diagnosis and decisions. In this study we analyze etiology and pattern of MF trauma and coexisting injuries if any. Patients and methods In the study MF injuries were diagnosed after evaluation of the patients’ history, physical examination, forensic record and radiological studies. Patients with isolated nasal and dentoalveolar fracture were excluded and in patients with suspected more severe facial injuries, maxillofacial CT scans were performed as proposed by our hospitals clinical policy. We retrospectively evaluated patients referred to our emergency department (ED) between 2010 March and 2013 March whose maxillofacial CT scans were obtained. Our study’s variables are presented as; age, gender, cause of injury, site of injury, alcohol consumption, coexisting intracranial, cervical, orthopedic, abdominal injuries and mortality if any. During the analyses Mid-face region injuries were classified as Le Fort I, Le Fort II, Le Fort III, blow out, zygomaticomaxillary complex, nasorbitoethmoid complex and zygomatic arc fractures.

Unless the challenges highlighted through the findings of this study are addressed and the opportunities capitalized, private land in biodiversity conservation will remain controversial and conflict ridden. The results from this study not only help understand the different attitudes that exist among stakeholders, but it also gives rise to more research questions such as the possible relationship between BV-6 supplier the expressed attitude

of landowners and their socio-demographic characteristics. Such information is also crucial to designing policies as well as to mitigate conflict that revolves around biodiversity conservation on private land in Poland. Acknowledgments The study described here was done as a part of the following Jagiellonian University Grants: Information, education and communication for the natural environment (WRBW/DS/INoS/760), and Investigating challenges

and opportunities in promoting biodiversity conservation on private land (DS/MND/WBiNoZ/INoS/16/2013). The authors would also like to express their gratitude to Dr Marcin Kocor (Institute of Sociology, Jagiellonian University, Krakow, Poland) for the technical advice and guidance he provided throughout this study. Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction click here in any medium, provided the original author(s) and the source are credited. References Alers M, Bovarnick A, Boyle T, Mackinnon K, Sobrevila C (2007) Reducing threats to protected areas: lessons from the field. IOP World Bank and UNDP. http://​siteresources.​worldbank.​org/​INTBIODIVERSITY/​Resources/​ReducingThreats-web.​pdf. Accessed 14 Dec 2013 Brown SR (1980) Political subjectivity: Applications of Q methodology in political science. Yale University Press, New Haven

Brown SR (1996) Q methodology and qualitative research. Health Res 6(4):561–567 Cent J, Kobierska H, Grodzińska-Jurczak M, Bell S (2007) Who is responsible for Natura 2000 in Poland? – a potential role of NGOs in establishing the programme. Int J Environ Sustain Dev 6:422–435CrossRef Central Diflunisal Statistical Office Poland (2012) Chapter 1: Environment and https://www.selleckchem.com/products/ldn193189.html Environmental protection. In Concise statistical yearbook of, Poland, pp 25–62 Cross RM (2005) Exploring attitudes: the case for Q methodology. Health Educ Res 20(2):206–213 Deignan T (2009) Enquiry-based learning: perspectives on practice. Teach High Educ 14:13–28CrossRef Doremus H (2003) A policy portfolio approach to biodiversity protection on private lands. Environ Sci Policy 6:217–232CrossRef European Commission (2013) Natura 2000 network. IOP European Commission: Environment. http://​ec.​europa.​eu/​environment/​nature/​natura2000/​. Accessed 20 Nov 2013 Environmental Law Institute (2003) Legal tools and incentives for private lands in Latin America: building models for success. Washington DC: Environmental Law Institute. https://​cmsdata.​iucn.

on gram-negative bacteria. Mikrobiologiia 2004, 73:320–325.PubMed 30. Gaeng S, Scherer S, Neve H, Loessner MJ: Gene cloning and expression and secretion of Listeria monocytogenes bacteriophage-lytic

enzymes in Lactococcus lactis . Appl Environ Microbiol 2000, 66:2951–2958.PubMedCrossRef 31. Leive L: Studies on the permeability change produced in coliform bacteria by ethylenediaminetetraacetate. J Biol Chem 1968, 243:2373–2380.PubMed 32. Schmelcher M, Waldherr F, Loessner MJ: Listeria bacteriophage peptidoglycan hydrolases feature high thermoresistance and reveal increased activity after divalent metal cation substitution. Appl Microbiol Biotechnol 2012, 93:633–943.PubMedCrossRef 33. Kuroda A, Sekiguchi J: Cloning, sequencing and genetic mapping of a Bacillus subtilis cell wall hydrolase gene. J Gen Microbiol 1990, 136:2209–2216.PubMed 34. Pritchard DG, Dong S, Baker JR, Engler JA: The bifunctional peptidoglycan www.selleckchem.com/products/pci-32765.html lysin of Streptococcus agalactiae bacteriophage B30. Microbiology 2004, 150:2079–2087.PubMedCrossRef

35. Marschutz MK, Caliceti P, Bernkop-Schnurch A: Design and in vivo evaluation of an oral delivery system for insulin. Pharm Res 2000, 17:1468–1474.PubMedCrossRef 36. Mokrasch LC: Use of 2,4,6-trinitrobenzenesulfonic acid for the coestimation of amines, amino acids, and proteins in mixtures. Anal Biochem 1967, 18:64–71.CrossRef 37. Hazenberg MP, de Visser H: Assay for N-acetylmuramyl-L-alanine amidase in serum by determination of muramic acid released from the peptidoglycan of Brevibacterium divaricatum www.selleckchem.com/products/ch5183284-debio-1347.html . Eur J Clin Chem Clin Biochem 1992, 30:141–144.PubMed Authors’ contributions BS, JL and SR designed the study. BS performed the experiments. HS carried out the sequence analysis. BS, JY, and SR analyzed the data and wrote the paper. SH critically reviewed the manuscript. All authors read and approved the final manuscript.”
“Background Sigma factors are subunits of the RNA polymerase complex responsible for specific recognition and melting of promoter DNA, which enable the polymerase to initiate transcription.

All eubacteria of known genome sequence code for at least one sigma factor, called primary, housekeeping or vegetative, and most encode additional sigma factors. For example, Streptomyces 5-Fluoracil solubility dmso coelicolor or Sorangium cellulosum carry as many as 60 to 80 GF120918 purchase predicted sigma factors [1, 2]. These so-called alternative sigma factors may be induced or activated by specific environmental signals, and consequently redirect transcription by competitively associating with the core RNA polymerase. Alternative sigma factors have been shown to mediate various cellular responses linked to stress conditions, growth transitions or morphological changes and development [1]. Sigma factors are classified into two structurally and evolutionarily distinct superfamilies [3], σ70 and σ54.

27 ± 0.44 1.10 ± 0.27 n.s. Total bilirubin (mg/dl) 1.44 ± 0.46 1.27 ± 0.47 n.s. Hemodialysis (Y/N) 2/37 4/7 0.017 ECMO use (Y/N) 0/39 2/9 0.045 DCL wound open care (Y/N) 21/18 7/4 n.s. Duration of laparotomy wound opened (days) 2.03 ± 2.91 1.11 ± 1.70 n.s Accumulated blood Trichostatin A Transfusion (U) 19.6 ± 4.16 32.9 ± 10.9 0.014 SD, Standard deviation; APACHI II, Acute physiology and chronic health evaluation II; GCS, Glasgow Coma Scale; PaO2, Arterial oxygen tension; FiO2, Fraction of inspiration oxygen; WBC, White cell count; Hb, Hemoglobin; PLT, Platelet; INR, International

normalized ratio, for prothrombin time; ECMO, Extracorporeal membrane oxygenation; DCL, Damage control laparotomy. Multivariable analysis Factors that were significant https://www.selleckchem.com/products/epz004777.html in abovementioned analyses were further enrolled for multivariable analysis. However, no significant variables were identified during further logistic regression analysis. Even when we enrolled only factors with p < 0.01, no factor remained statistically and independently significant. Discussion DCL is a life-saving procedure. When this procedure is indicated, patients usually

do not have any other choice for their treatment. The basic rationale of DCL is for hemorrhage and contamination control at the early, life-threatening period. After the DCL, the clinicians then return patients to relatively stable conditions, so the patients can undergo definitive surgical treatment at the next stage. Even with the development of new strategies to manage and

resuscitate patients with severe trauma [8, 9] and the lack of high level supporting evidence [10], DCL still plays an important role in trauma care, even though some clinicians have reflected on its Amrubicin futility [11, 12]. Although DCL can bridge a patient with exsanguination from a devastating condition to a stage for definitive treatment, some patients still succumb to their critical condition even after successful hemostasis. In this study, we explored the factors that influenced patients’ outcomes after initially successful hemostasis. Our analysis included 3 different parts: demographic data and clinical MI-503 nmr conditions upon arrival at the ED, perioperative conditions, and early ICU parameters and intervention. In the univariable analysis, most of the significant factors were noted in the initial ED stage and the early ICU stage, while an analysis of perioperative factors revealed minimal survival impact. Initial hypoperfusion (pH, BE, and GCS level) and initial poor physiological conditions (body temperature, RTS, and CPCR at ED) may contribute to a patient’s final outcome. These factors are similar to the risk factors that were proposed by previous studies [13, 14], while RTS itself has served as a surrogate for survival prediction [15, 16]. The parameters recorded during the initial ICU admission represent the clinical conditions immediately after DCL.

2 %) with

proteinuria before TSP into groups C (N = 25) and D (N = 13), with or without proteinuria 3–5 years after TSP, respectively (Fig. 3a). There was a significant difference in serum Gd-IgA1 levels, but not in IgA/IgG-IC levels, before TSP in both groups [group C vs D, Gd-IgA1 (U/mg Etomoxir IgA); 102.2 ± 37.6 vs 133.3 ± 41.4, P = 0.03, IgA/IgG-IC (OD); 0.81 ± 0.30 vs 0.98 ± 0.33, P = 0.11). Cross-sectional analysis indicated significant correlations between proteinuria severity and serum Gd-IgA1 and IgA/IgG-IC levels. However, the percentage decreases in Gd-IgA1 (P = 0.87) and IgA/IgG-IC (P = 0.52) serum levels after TSP were not significantly different between the 2 groups (Fig. 3b). Fig. 3 Longitudinal analysis of patients with proteinuria. Thirty-eight patients with proteinuria before TSP were divided into groups C and D, with or without proteinuria 3–5 years after TSP (a). Cross-sectional analysis revealed significant correlations between severity of proteinuria and serum Gd-IgA1 and IgA/IgG-IC levels, but the percentage decrease in serum Gd-IgA1 and IgA/IgG-IC levels did not differ between the groups (b) The average percentage

decrease in IgA/IgG-IC levels before and after 3–5 years was 20 ± 17 in all patients. Next, we divided the patients according to the average percentage decrease in IgA/IgG-IC serum levels before TSP and 3–5 years after TSP into large delta IC (>20) and small delta IC (≤20) groups,

and analyzed laboratory data for the patients in the large delta IC group. In this large delta IC group see more (N = 25; 50 %) of patients who had a greater than average percentage decrease (>20) in IgA/IgG-IC serum levels, proteinuria after 3–5 years was persistent only in 4 patients (16 %) who had severe sclerotic glomerular lesions before TSP (data not shown). EPZ015666 price Discussion This is the first report to demonstrate that assessment of IgAN activity based on urinary abnormality correlates with changes in serum levels of Gd-IgA1 and IgA/IgG-IC. This study indicates that Gd-IgA1 and IgA/IgG-IC could be extremely useful components for evaluation of IgAN activity in a noninvasive manner. Annual routine screening for urinary abnormalities is conducted in school-aged children to adults in Japan [12, 13], and these screening procedures Carnitine palmitoyltransferase II markedly increase the percentage of early stage IgAN patients presenting with microscopic hematuria and the overall IgAN prevalence. Indeed, chance microscopic hematuria is a leading event for renal biopsy in Japan [5, 7–10, 12, 13]. This observation suggests that hematuria is an initial manifestation of early stage IgAN and a primary manifestation of active IgAN. Recent studies revealed abnormalities of IgA1 glycosylation and formation of autoantibodies to these aberrantly glycosylated IgA1 molecules as key factors in the pathogenesis of IgAN [17–20].

J Toxicol Environ Health A 2008, 71: 887–897.CrossRefPubMed 33. Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ 1997, 315: 629–634.PubMed 34. Terrin N, Schmid CH, Lau J: In an empirical evaluation

of the funnel plot, researchers could not visually identify publication bias. J Clin Epidemiol 2005, 58: 894–901.CrossRefPubMed 35. Lau J, Ioannidis JP, Terrin N, Schmid CH, Olkin I: The case of the misleading funnel plot. BMJ 2006, 333: 597–600.CrossRefPubMed Competing interests The authors declare that they have no competing interests. Authors’ contributions XZ and LC conceived of the study, and carried out the analysis of the literatures and drafted the manuscript. ZX carried out the collection of the literatures. QL Smad3 phosphorylation helped with the statistical analysis and manuscript drafting. XZ conceived of the study, and participated in its design and coordination and helped Erismodegib clinical trial to draft the manuscript. All authors read and approved the final manuscript.”
“Background A multinucleated cell is a unique form which is frequently observed in the normal tissue. Skeletal muscle is composed of bundles of multinucleate muscle fibers [1]. Osteoclasts induce

multinucleation by the cell fusion of mononuclear cells to cover a large area for bone resorption [2]. Macrophages may fuse to form multinuclear giant cells when adequately ADP ribosylation factor stimulated [3]. Many hepatocytes are binucleate, and the nuclei are frequently polyploidy [4]. On the other hand, multinucleated cells are frequently seen in malignant neoplasms. Giant cells may be formed and possess either one enormous nucleus or several nuclei [5]. In Hodgkin’s disease, Reed-Sternberg cells have an intricate double or bi-lobed nucleus [6]. The mechanism of neoplastic multinucleation remains unknown, but is considered to be induced by cell-cell fusion or acytokinetic cell division. Myxofibrosarcoma is one of the most common sarcomas in elderly patients with a slight male predominance and this

tumor consists of spindled and pleomorphic tumor cells and bizarre multinucleated giant cells with abundant eosinophilic cytoplasm [7]. Some of these multinucleated cells are considered to be neoplastic and possess atypical nuclei or mitotic changes [8]. However, it is not known precisely by what mechanism multinucleated cells are formed. To determine whether the mechanism of multinucleation is cell-cell fusion or acytokinetic cell division, we elucidated the activity of the multinucleated cells by Ki-67 immunohistochemistry and the dynamics and differentiation by live-cell video selleck compound microscopy in the two myxofibrosarcoma cell lines. Methods Tumor cell lines The human myxofibrosarcoma cell lines, NMFH-1 and NMFH-2, were used for these experiments. NMFH-1 was described previously [9]. NMFH-2 has been newly established in our institute.

The most recent advisory committee meeting, which dealt with the issue of adult acetaminophen overdose, was conducted in 2009 and formed the basis for current decisions that are being made by the FDA and Caspase activity assay industry about

how to dose acetaminophen in both nonprescription and prescription products.[9] To address the issues surrounding acetaminophen toxicity, the FDA Center for Drug Evaluation and Research (CDER) prepared an internal report that formed the basis for discussion at the 2009 advisory committee meeting. The committee members were asked to vote upon several recommendations, which included reducing the total daily acetaminophen dose from 4000 mg to 3250 mg, limiting tablet strength selleck compound to 325 mg/tablet, and switching the 500 mg strength to prescription status.[9] The advisory beta-catenin phosphorylation committee was generally sympathetic to these interventions as ways to reduce acetaminophen toxicity.[9] As with all

advisory committees, the committee was purely ‘advisory’ to the FDA, and its recommendations were not binding to the FDA. However, the recommendations of the CDER group and the advisory committee and subsequent actions by the FDA and voluntary actions by industry have created significant confusion about the therapeutic or ‘proper’ dose of acetaminophen. What is the maximum safe daily dose of acetaminophen? In reality, the FDA has never validated the threshold toxic dose for the average adult. The 3900 mg maximum daily dose, as recommended originally, was deemed to be safe and is five to seven times lower than the estimated median lethal dose (LD50) of 400 mg/kg. The 1977 panel used anecdotal reports suggesting that 15 g was the hepatotoxic dose; therefore, a dose of 650 mg was 23 times less than the hepatotoxic dose. Subsequently, the analgesic monograph dictated that 3900–4000 mg was a safe and effective maximum daily dose if acetaminophen

was used properly and according to the approved labeling. History has demonstrated the safety of this dose. In 1994, Whitcomb and Block published the results of their retrospective case series review of 126 779 hospital discharge summaries from the University of Pittsburgh Medical Center to identify those patients who were taking acetaminophen and who developed severe hepatotoxicity.[10] Phosphoglycerate kinase Forty-nine patients with severe acetaminophen-induced hepatotoxicity (defined as an aspartate aminotransaminase level >1000 U/L) were identified: 28 patients had an intentional acetaminophen overdose, and 21 were taking acetaminophen for therapeutic reasons. All of these patients had taken more than the recommended daily maximum dose of 4000 mg. No hepatotoxicity was identified in patients who had therapeutic doses of acetaminophen or less than 4000 mg/day. A prospective study by den Hertog and colleagues evaluated the use of acetaminophen in 697 stroke patients who received a dose of 6000 mg daily for 3 days. None of the patients had liver enzyme changes.

It shows two main features: the D and G bands. The first band at around 1,331 cm-1 originated from atomic displacement and disorder caused by structural defect

[21]. The second one at around 1,599 cm-1 indicates the graphitic state of bamboo MWNTs. Cilengitide mw Moreover, the intensity ratio of D to G (I D/I G) is measured to be 1.14. This suggests a certain degree of orderly graphitic structure in the prepared nitrogen-doped MWNTs, which is consistent with the observed TEM results. The TGA is used to investigate the distribution and species of the carbon phases present in CNTs. Figure 3 shows the derivative of TGA curve of the nitrogen-doped MWNTs. The weight loss is considered due to the combustion of carbon in air atmosphere and represents more than 97% of carbon content for the prepared sample with oxidation peak at 550°C.

Consequently, this shift in the mass loss maxima suggests more defects and disorders for the nitrogen-doped MWNTs which are in Selleckchem Vactosertib good agreement with the Raman results. Figure 2 Raman spectrum of N-MWNTs. Figure 3 Derivative of TGA curve of N-MWNTs. Characterization of nanocomposites (HDPE/N-MWNTs) The SEM images for the nanocomposites were taken without any treatment at two different magnifications. The nanocomposite cross-sectional surface for 0.8 wt.% N-MWCNT content is represented in Figure 4, where the N-MWNT in HDPE is clearly observed even at low Selleck Smoothened Agonist loadings of MWNT in the composites. The Raman analysis for this nanocomposite presented in Figure 5 shows the presence of the D and G bands in the background as a result of the relatively low concentration of MWNT in polymer. However, the presence of carbon nanostructures can still be easily detected, and their Raman feature peaks are located at similar bandwidth as the ones in the pristine material. Figure 4 SEM micrographs of HDPE/N-MWNT nanocomposite. Figure 5 Raman shift

Lonafarnib of HDPE/N-MWNT nanocomposite. On the other hand, the larger intensity reflections are the bands resulting from the HDPE matrix as reported in the literature [22]. The band at 1,080 cm-1 is used to characterize the level of amorphous phase in HDPE. Indeed, Raman spectroscopy is one of the most powerful tools to characterize the crystallinity of HDPE [22], and this is made through the intensity measurement between 1,400 and 1,460 cm-1. Those bands are characteristics of the methylene bending vibrations. In particular, the band in the 1,418 cm-1 region is typically assigned to that of the orthorhombic crystalline phase in polyethylene [22–24]. Furthermore, Figure 6 shows the X-ray diffraction (XRD) patterns of the pristine HDPE and nanocomposites filled with N-MWNTs. The pristine HDPE mainly exhibits a strong reflection peak at 21.6° followed by a less intensive peak at 24.0°, which correspond to the typical orthorhombic unit cell structure of (110) and (200) reflection planes, respectively.

LY2603618 admixture refers to the process by which two discrete populations exchange genetic material resulting in organisms that this website have a genome that is sourced from two different origins. BAPS analysis will, for each sequence, estimate the proportion of genetic material arising from organisms from each of the clusters that are derived as part of the analysis. It will also

assign a p value to the likelihood of an organism being admixed. The data shows that it is likely that strains belonging to STs 47, 54, and 179 have significant admixture and that there was not enough information in the seven loci to show this when performing the initial BAPs clustering. This hypothesis was tested selleck chemical further by applying the same BAPS sequence-based clustering that was originally used to generate the clusters from 838 ST to a larger dataset which became available at the end of the study (1020 STs). These data are reported for the STs found in clusters 3 and 7 (Table  4). With the increased data available from 1020 STs the probability of these STs being admixed is now significant and it would not be possible to assign these STs to a cluster with statistical confidence. However for both ST62 and ST337 there is no significant admixture

within either of the data sets and it is likely therefore that these are good representative strains for clusters 3 and 7 respectively. Table 4 Table showing admixture of Legionella pneumophila strains Cluster ST Proportion of genetic material from clusters (838 strain data set) Significant admixture? (838 strain data set) Admixture analysis with 1020 strains Significant Thymidylate synthase admixture? (1020 strain data set) 3 47 3: 0.77, 1:0.21 no 3: 0.36, 1:0.29, 11: 0.35 yes 3 54 3: 1.0 no 3: 0.72, 10:0.24 yes 3 62 3: 1.0 no 3: 0.97 no 7 179 7: 0.85, 13:0.14 no 7: 0.56, 13: 0.35 yes 7 337 7: 0.96 no 7: 1.0 no The clusters

listed are those that show aberrant clustering on both trees derived from whole genome data. Only those clusters (cluster numbers shown in bold text) that contribute more than 0.1 of the genetic material of a strain are reported. In the original BAPS analysis STs 1, 5 and 152 were all assigned to cluster 6 with no significant admixture despite ST5 being in a separate clade on the phylogenetic tree derived from the seven locus sequence data. The prediction from this data was that whole genome data would show these strains to have similar ancestral origins. Both whole genome trees show this to be the case with all three STs clustering tightly in one branch of the tree. Conclusions This paper describes the sequencing of multiple genomes from strains representing most of the diversity present in the L. pneumophila population sampled from both environmental sources associated with human habitation and from patients with Legionnaires’ disease.

PubMedCrossRef 46. Augustyns K, Van Aerschot A, Van Schepdael A, Urbanke C, Herdewijn P: Influence of the incorporation of (S)-9-(3,4-dihydroxybutyl)adenine on the enzymatic stability and base-pairing properties of oligodeoxynucleotides.

Nucleic Acids Res 1991, 19:2587–2593.PubMedCentralPubMedCrossRef Competing interests The authors declare that they have no conflict of interests. Authors’ contributions MO conceived the study and carried out the molecular genetic studies. MN participated in the design of the study, carried out the molecular GSI-IX genetic studies and drafted the manuscript. JK participated in the design of study and drafted the manuscript. All the authors have read and approved the final manuscript.”
“Background Autotransporter proteins are the largest known family of virulence factors expressed by Gram-negative bacteria and play prominent roles in processes such as invasion [1], serum resistance [2, 3], phospholipolysis [4–6], cytotoxicity [7], adherence [8, 9], survival within eukaryotic cells [10], intracellular motility [11], cell-to-cell aggregation [12, 13], and biofilm formation [14, 15]. These molecules display conserved structural features including an N-terminal surface-exposed domain responsible SN-38 for the biological function and a hydrophobic C-terminus that tethers the autotransporter to the outer membrane (OM). Based on the learn more structure of the C-terminus, autotransporters

can be classified as conventional or oligomeric [16–21]. The C-terminus of conventional autotransporters consists of ~300 amino acids (aa) forming 10–12 antiparallel β-strands, while that of oligomeric autotransporters is substantially shorter (~70 aa) and specifies only 4 β-strands. Because

of their structure and 3-mercaptopyruvate sulfurtransferase role in virulence, autotransporters are attractive targets for developing countermeasures against pathogenic organisms. Large portions of autotransporters are located on the bacterial surface and therefore readily accessible for recognition by the immune system. Additionally, autotransporters play important roles in pathogenesis, thus targeting them may hinder the ability to cause disease. This hypothesis is supported by several studies demonstrating the effectiveness of autotransporter-based countermeasures. For example, immunization with Neisseria meningitidis NadA elicits antibodies (Abs) binding to the bacterial surface and promoting complement-mediated killing [22, 23], which is key to protection against this organism. Antibodies against Haemophilus influenzae Hap block adherence to epithelial cells and immunization with Hap protects mice in nasopharyngeal colonization studies [24, 25]. Vaccination with the Proteus mirabilis autotransporter cytotoxin Pta yields Abs that not only reduce bacterial burden in a murine urinary tract infection model, but also neutralize the cytotoxic activity of Pta for bladder cells [26].