Type II TA systems are typically two-gene operons with the antitoxin encoded upstream of the toxin gene. The proteic antitoxins bind their cognate toxins and inhibit toxin activity. Antitoxins or

toxin-antitoxin complexes autorepress TA module transcription. Under stressful environmental conditions such as nutrient limitation, antibiotic therapy, or oxidative stress, TA modules are activated. The labile antitoxin is degraded by either the Lon or Clp proteases and the more stable toxin is freed to facilitate growth arrest. Many toxins are mRNA-specific RNases that rapidly inhibit protein synthesis, inducing a bacteriostatic state. Upon improved conditions (or removal of stress), antitoxin synthesis resumes to counteract toxin activity, and tmRNA activity rescues ribosomes KPT-330 arrested on toxin-cleaved messages [21, 22]. Virulence-associated protein (vap) genes, first identified in pathogenic strains of the Gram-negative, strict click here anaerobe

Dichelobacter nodosus, are found as transmissible genetic elements for the transfer of virulence determinants [23]. The vap genes are recognized as a part of pathogenicity islands (PAI), a group of laterally-transferred genes in the bacterial genome, which help the organism explore and adapt to new ecological niches [24, 25]. Four vap operons, toxAvapA, vapBC-1, vapBC-2, and vapXD have been identified in the genomes of numerous NTHi strains, including Rd KW20 [26], R2866 [27], and 86-028NP [28]. mTOR inhibitor All vap operons display the characteristic features of type II TA modules, and vapBC-1 and vapXD have been shown to act as TA loci in NTHi [29, 30]. During recurrent and chronic otitis media, NTHi are exposed to hostile conditions such as antibiotic treatment, host immune responses, and nutrient deprivation. It is thought that a subpopulation of NTHi can resume the infection after cessation of these stressors, resulting

in a persistent infection. Although TA modules function to allow bacterial adaptation to environmental stresses, the pathogenic roles of the NTHi vapBC-1 and vapXD operons have not been elucidated in otitis media. It has been shown that the protein products of canonical type II TA loci interact to form protein complexes that autoregulate their cognate promoters [22]. Accordingly, we examined the heterodimerization characteristics of the VapB-1 antitoxin with the VapC-1 toxin, as well as interactions of the antitoxin VapX with the toxin VapD. We then constructed vapBC-1, vapXD, and vapBC-1 vapXD double deletion mutants in strain 86-028NP. The survival properties of these mutants were compared to the wild type parent strain during long-term infections of a primary human respiratory epithelial tissue at the air-liquid interface (ALI), the EpiAirway™ tissue.

Emerg Med J 2007, 24:170–174.PubMedCentralPubMedCrossRef 5. Gerdtz MF, Chu M, Collins M, et al.: Factors influencing consistency of triage using the Australasian Triage Scale: implications for guideline development. Emerg Med Australas 2009, 21:277–285.PubMedCrossRef 6. van Mello NM, Zietse CS, Mol F, et al.: Severe maternal morbidity in ectopic pregnancy is not associated with maternal factors but may be associated with quality of care. Fertil Steril 2012, 97:623–629.PubMedCrossRef 7. Huchon C, Fauconnier A: Adnexal torsion: a literature review. Eur J Obstet Gynecol Reprod Biol 2010, 150:8–12.PubMedCrossRef 8. Dewitt J, Reining A, Allsworth JE, Peipert

JF: Tuboovarian abscesses: is size associated with duration of hospitalization Sorafenib nmr & complications? Obstet Gynecol Int 2010, 2010:847041.PubMedCentralPubMedCrossRef 9. Popowski T, Huchon C, Toret-Labeeuw F, Chantry AA, Aegerter P, Fauconnier A: Hemoperitoneum assessment in ectopic pregnancy. Int J Gynaecol Obstet 2012, 116:97–100.PubMedCrossRef

10. Huchon C, Panel P, Kayem G, et al.: Is a standardized questionnaire useful for tubal rupture screening in patients with ectopic pregnancy? Acad Emerg Med 2012, 19:24–30.PubMedCrossRef 11. Huchon C, Panel P, Kayem G, Schmitz T, Nguyen T, Fauconnier A: Does this woman have adnexal torsion? Hum Reprod 2012, 27:2359–2364.PubMedCrossRef 12. Colaizzi PF: Psychological Research as the Phenomenologist Views It. In Existential-Phenomenological Alternatives Temozolomide for Psychology. Edited by: Valle RS, King G. New York: Oxford University Press; 1978:48–71. 13. Ankum WM, Van der Veen F, Hamerlynck JV, Lammes FB: Transvaginal sonography and human chorionic gonadotrophin measurements in suspected ectopic pregnancy: a detailed mafosfamide analysis of a diagnostic approach. Hum Reprod 1993, 8:1307–1311.PubMed 14. Mol BW, van Der Veen F, Bossuyt PM: Implementation of probabilistic decision rules improves the predictive values of algorithms in the diagnostic management of ectopic pregnancy. Hum Reprod 1999, 14:2855–2862.PubMedCrossRef 15.

Kahn JG, Walker CK, Washington E, Landers DV, Sweet RL: Diagnosing pelvic inflammatory disease. A comprehensive analysis and consideration for devellopping a new model. JAMA 1991, 226:2594–2604.CrossRef 16. Soper DE: Pelvic inflammatory disease. Infect Dis Clin 1994, 4:821–840. 17. Barnhart KT, Fay CA, Suescum M, et al.: Clinical factors affecting the accuracy of ultrasonography in symptomatic first-trimester pregnancy. Obstet Gynecol 2011, 117:299–306.PubMedCrossRef 18. Fauconnier A, Mabrouk A, Salomon LJ, Bernard JP, Ville Y: Ultrasound assessment of haemoperitoneum in ectopic pregnancy: derivation of a prediction model. World J Emerg Surg 2007, 2:23.PubMedCentralPubMedCrossRef 19. Soper DE: Pelvic inflammatory disease. Obstet Gynecol 2010, 116:419–428.PubMedCrossRef 20.

The time we had during our project was enough to develop an approach to identify the different issues to be included in a monitoring system (i.e. time, seasonal calendar, people’s availability, necessity of a multi-stakeholder engagement, selection of simple but important

NTFPs). The repetition of assessments and measurements, and data quality control needs regular visits to the monitored villages. In our case, the 2 year-duration of our research was not enough to achieve long-term impacts. It did not allow real testing. We were only able to test the monitoring system for 6 months, which did not cover a full season of NTFP collection. Unpredictable events were among the limitations we identified for full implementation of the monitoring system. We recommend at least two cycles of NTFP harvest (i.e. 2 years), which would allow comparison, to test the approach and learn from the results. Integration into check details national policies (here PLUP)

was in progress at the end of the project (Lestrelin et al. 2011, Bourgoin and Castella 2011, Bourgoin et al. 2012), but we lacked time to discuss with decision-makers ways the monitoring could be used to selleck chemical assess the impact of LUP and to scale up. Scaling up The monitoring system developed in Laos has the potential to address multi-stakeholders’ concerns: villagers, including local elites, local authorities at the kumban and district levels, and organizations working on community development and conservation. Integrating these management practices into multi-level and multi-scale governance could support win-win solutions for both the villagers (data to negotiate) and the district authorities (data to deliver to the provincial level). If embedded in existing local governance and applied in key government policies, it could

Resveratrol be used as a tool to empower local communities. This could be achieved by providing them with information on the effects of land management policies on forest resources and livelihoods. The different steps we propose could be applied easily to different situations elsewhere in the country. This could be with different ethnic groups, involving villages at different steps of rural transition, and different scales, from the village level to the village cluster and to the landscape. For the time being, we can only share the potential of this approach and call for more implementation trials before expanding it to different situations and provinces in the country. Acknowledgments The authors thank the Viengkham community for their participation to their activities. They also thank Glen Mulcahy, Douglas Sheil and the anonymous reviewer for their valuable comments and editing, and Mohammad Agus Salim for designing the maps. They acknowledge the Swiss Agency for Development and Cooperation (SDC) and the European Commission for their financial support.

The reaction was visualized by the CheMate™ DAB plus Chromogen. Lastly, the sections were counterstained with hematoxylin solution. Negative controls were performed by staining with primary antibody. The stained sections were evaluated and scored for staining intensity and% of staining under a light microscope, i.e., percentage

of staining was documented as 0 (<5%), 1 (5%-25%), 2 (26%-50%), 3 (51%-75%), and 4 (>75%). Staining intensity was documented as 0 (no immunostaining), 1 (weak), 2 (moderate), and 3 (strong). The value of these CDK inhibitor two scores were added together to garner a final score for each case: a scale of 0 (score less than 2), 1+ (score range from 2 to 3), 2+ (score range from 4 to 5), and 3+ (score range from 6 to 7). Immunostaining was assessed by an experienced pathologist who was blinded to the clinical data of the patients. Construction of GKN1 expression vector for gene transfection GKN1 cDNA was amplified from total RNA of the normal gastric mucosa using PCR. GKN1 CDS fragments with SalI and BamHI restriction sites were then inserted into the pBudCE4.1 vector (Invitrogen, Carlsbad, CA, USA) using a DNA ligation kit from TaKaRa (Dalian, China). After transformation into DH5α E. Coli competent cells, the plasmid was amplified and the DNA sequence was then confirmed. To generate gastric cancer cells expressing GKN1, gastric cancer AGS cells

were grown to 50–75% confluency in a six-well plate, washed twice with RPMI lacking supplements (RPMS/LS), and subjected to the Lipofectamine-mediated transfection according to the manufacturer’s protocol (Invitrogen). The GKN1 transfected Ivacaftor purchase gastric cancer cells were then selected in medium containing Zeocin (Invitrogen). After the transfected cells formed individual cell colonies, stable cells were obtained and then confirmed for GKN1 expression by using RT-PCR and Western blot analyses.

Cell viability (MTT) assay To detect changes in tumor cell viability after GKN1 transfection, a total of 1 × 104 trypsin-dispersed cells in 0.1 mL culture medium was seeded into each well of a 96-well plate, and cultured for 24 h or 48 h. Next, 20 μL of MTT (5 g/L from Sigma-Aldrich, St. Louis, USA) was added to each well and incubated for additional 4 h at 37°C. Culture medium was then replaced with 200 μL of dimethyl sulfoxide (DMSO) and the absorbance Unoprostone rate was determined using an ELISA reader at 490 nm. Cell growth inhibition rate was calculated as (the value of experimental group OD /the value of control group OD) × 100%. Annexin V apoptosis assay To detect tumor cell apoptosis, the GKN1 transfected tumor cells were seeded into 60-mm diameter culture plates, and cultured for 24 h and 48 h. The apoptotic rates were analyzed by flow cytometry using an annexin V-FITC/PI kit. Staining was performed according to the manufacturer’s instructions, and flow cytometry was conducted with a flow cytometer (Beckman-Coulter, Brea, USA).

This information, completed with the new results extracted from the other techniques, finally provide new information about the HCN black polymers. Chen, Q. W. and Chen, C. L. (2005). The role of inorganic compounds in the prebiotic synthesis of organic molecules. Current. Org. Chem. 9, 989–998. Ferris, J. P., Donner, D. B., Lobo, A. P. (1973). Possible role of hydrogen Copanlisib cyanide in chemical evolution. Investigation on the proposed direct synthesis of peptides from hydrogen cyanide. J. Mol. Evol. 74, 499–508. Ferris, J. P., Joshi, P. C., Edelson, E. H., Lawless, J. G. (1978).

HCN: A plausible source of purines, pyrimidines, and amino acids on the primitive Earth. J. Mol. Evol. 11, 293–311. Ferris, J. P., Edelson, E. H., Auyeung, J. M., Joshi, P. C. (1981). Structural studies on HCN oligomers. J. Mol. Evol. 17, 69–77. Matthews, C. N., Moser, R. E. (1967). Peptide synthesis from hydrogen cyanide and water. find more Nature 215, 1230–1234. Matthews, C. N. and Minard, R. D. (2006). Hydrogen

cyanide polymers, comets and the origin of life. Faraday Discuss, 133, 393–401. Saladino, R., Crestini, C., Costanzo, G., DiMauro, E. (2004) Advances in the prebiotic synthesis of nucleic acids bases: Implications for the origin of life. Current Org. Chem. 8, 1425–1443. Umemoto, K., Takahasi, M., Yokota, K. (1987). Studies on the structure of HCN oligomers. Origins of Life 17, 283–293. Voet, A. B., Schwartz, A. W. (1983). Prebiotic adenine synthesis from HCN-Evidence for a newly discovered major pathway. Biorg. Chem. 12, 8–17. Völker, T. (1960). Polymere Blausäure. Angew. Chem. 72, 379–384. E-mail: ruizbm@inta.​es Divalent Metal Ion as a Prebiotic Catalyst for Nucleotidyl Transfer to Form Coenzymes and Ribonucleoitdes Containing Pyrophosphate Bond Hiroaki. Sawai Department of Applied Chemistry and Chemical Biology, Gunma University, Kryuu, Gunma 376–8515 Japan We previously reported model reactions of prebiotic synthesis of RNA from nucleoside-5′-phjosphorimidazolides

(ImpN) by divalent metal ion catalyst such as UO22+, Pb2+, and Zn2+ ion. OligoRNAs from 2mer to 18mer were formed by 17-DMAG (Alvespimycin) HCl the reaction in neutral aqueous solution. The reaction takes places by transfer of ribonucleotidyl group of ImpN to the 2′- or 3′-OH group of adjacent molecule of ImpN formiong the phosphodiester bond. Apart from RNA, another group of biologically important compounds consisting of ribonucleotides containing pyrophosphate are prepared by ribonulceotidyl transfer reactions and play essential roles in life. For example, coenzymes such as NAD, FAD and Coenzyme A are involved in the enzymatic oxidation-reduction and acyl transfer reactions, respectively. Sugar-nucleotides such as UDP-glucose are precursors of polysaccharide biosynthesis, and CDP-choline is a precursor of lipid biosy.nthesis.

In contrast up regulation of genes encoding cation transport systems (mnhB_1, mnhC_1, mnhD_1, mnhF_1, mnhG_1) was found. Figure 7 Heatmap of RNA Sequencing comparing JKD6159 ( aryK inactive) to JKD6159_AraC r ( aryK intact). RNA seq was performed in duplicate from stationary phase cultures. This heatmap, clustered on expression profiles, was created based on log2 transformed counts to identify consistent changes in expression profiles between www.selleckchem.com/products/ganetespib-sta-9090.html strains. To be included in the heat map, genes were required to have at least 1000 counts (reads), totaled over all samples, where the standard deviation of log2 expression differences had to exceed two. The heatmap highlights

significant aryK-dependent changes, in particular genes involved in the regulation of central metabolic functions. Here, we have clearly demonstrated that agr is the major “”on-off”" switch Palbociclib cost for virulence in ST93 CA-MRSA, but we also found that other genetic changes are impacting virulence gene regulation in a clone-specific manner. We speculate that the inactivation of aryK may have been an evolutionary response by ST93 CA-MRSA to modulate or fine-tune the amount of Hla and other factors required for host persistence. There are six AraC/XylS family regulators in S. aureus (SA0097, SA0215, SA0622, SA1337, SA2092, SA2169; S. aureus

strain N315 locus tags). Two of these, Rbf (SA0622) and Rsp (SA2169) have been studied and demonstrated in other S. aureus strains to regulate biofilm formation and modulate expression of surface-associated proteins [24,

25, 31]. In contrast, we found that aryK increases Hla expression and virulence, acting as a positive regulator of virulence by directly or indirectly upregulating exotoxin expression, without an apparent effect on agr expression in stationary phase. Conclusions In this study, we have obtained insights into the genetic basis for the increased virulence of ST93 by using a combination of comparative and functional genomics. We have demonstrated the key role of Hla and agr and shown how an additional novel regulatory gene, aryK by a loss-of-function point mutation, is modulating virulence in this clone. Quantification of exotoxin expression in a larger collection of ST93 strains demonstrated that the findings in strain JKD6159 are relevant to the majority of mafosfamide the ST93 population isolated from around Australia as exotoxin expression in JKD6159 is representative of most of the ST93 population. Our study highlights the power of comparative genomics to uncover new regulators of virulence but it also shows the complex nature of these changes even in closely related bacterial populations. Careful strain selection, detailed comparative genomics analyses, and functional genomic studies by creating multiple genetic changes in one strain will be required to gain a full insight into the genetic basis for the emergence and hypervirulence of ST93 CA-MRSA.

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Huang X, Xu H, Sun X, Ohkusu K, Kawamura Y, Ezaki T: Genome-wide scan of the gene expression kinetics of Salmonella enterica Serovar Typhi during hyperosmotic Stress. Int J Mol Sci 2007, 8:116–135.CrossRef 23. Gantois I, Ducatelle R, Pasmans F, Haesebrouck F, Hautefort I, Thompson A, Hinton JC, Van Immerseel F: Butyrate specifically down-regulates salmonella pathogenicity island 1 gene expression. Appl Environ Microbiol 2006,72(1):946–949.PubMedCrossRef 24. Becker D, Selbach M, Rollenhagen C, Ballmaier M, Meyer TF, Mann M, Bumann D: Robust Salmonella metabolism limits possibilities for new antimicrobials. Nature 2006,440(7082):303–307.PubMedCrossRef 25. Adkins JN, Mottaz HM, Norbeck AD, Gustin JK, Rue J, Clauss

TR, Purvine SO, Rodland KD, Heffron F, Smith RD: Analysis of the Salmonella typhimurium learn more check details proteome through environmental response toward infectious conditions. Mol Cell Proteomics 2006,5(8):1450–1461.PubMedCrossRef 26. Shi L, Adkins JN, Coleman JR, Schepmoes AA, Dohnkova A, Mottaz HM, Norbeck AD, Purvine SO, Manes NP, Smallwood HS, et al.: Proteomic analysis of Salmonella enterica serovar typhimurium isolated from RAW 264.7 macrophages: identification of a novel protein that contributes to the replication of serovar typhimurium inside macrophages. J Biol Chem 2006,281(39):29131–29140.PubMedCrossRef 27. Manes NP, Gustin JK, Rue J, Mottaz HM, Purvine SO, Norbeck AD, Monroe ME, Zimmer JS, Metz TO, Adkins JN, et al.: Targeted protein degradation by PTK6 Salmonella under phagosome-mimicking culture conditions investigated using comparative peptidomics. Mol Cell Proteomics 2007,6(4):717–727.PubMedCrossRef

28. Ansong C, Yoon H, Norbeck AD, Gustin JK, McDermott JE, Mottaz HM, Rue J, Adkins JN, Heffron F, Smith RD: Proteomics analysis of the causative agent of typhoid fever. J Proteome Res 2008,7(2):546–557.PubMedCrossRef 29. Christman MF, Morgan RW, Jacobson FS, Ames BN: Positive control of a regulon for defenses against oxidative stress and some heat-shock proteins in Salmonella typhimurium . Cell 1985,41(3):753–762.PubMedCrossRef 30. Morgan RW, Christman MF, Jacobson FS, Storz G, Ames BN: Hydrogen peroxide-inducible proteins in Salmonella typhimurium overlap with heat shock and other stress proteins. Proc Natl Acad Sci USA 1986,83(21):8059–8063.PubMedCrossRef 31. Ishihama Y, Sato T, Tabata T, Miyamoto N, Sagane K, Nagasu T, Oda Y: Quantitative mouse brain proteomics using culture-derived isotope tags as internal standards. Nat Biotechnol 2005,23(5):617–621.PubMedCrossRef 32. Ong SE, Mann M: A practical recipe for stable isotope labeling by amino acids in cell culture (SILAC).

7%, sensitivity to complement-mediated phagocytosis did not differ between the 12030 wild type and 12030ΔbgsB (Additional file 2). Furthermore, rabbit antibodies raised against whole bacterial cells of E. faecalis 12030 mediated opsonophagocytic killing of 12030ΔbgsB comparable U0126 to levels obtained for the wild-type strain (Additional file 2). The loss of glycolipids from the cell membrane is associated with reduced adherence to Caco-2 cells and impaired biofilm formation We recently showed that deletion of bgsA leads to loss of biofilm formation on polystyrene and to reduced adherence to Caco-2 cells [5]. Partial deletion of bgsB also strongly impaired biofilm formation, reducing production

by 50% (Figure 3). This defect in biofilm formation was not a result of decreased initial attachment (i.e., bacteria attached in ≤ 30 min of incubation); rather, it was due to defective accumulation of biofilm mass after initial attachment (Figure 3). Over a period of 24 h, biofilm mass of wild-type bacteria on polystyrene grew in a linear fashion. In contrast, the amount of biofilm produced by bgsB and bgsA mutants selleckchem remained constant at the level of initial attachment. Adhesion to colonic epithelial cells (Caco-2 cells) was also impaired in 12030ΔbgsB, reaching only 50% of the adhesion of wild-type bacteria (Figure 3).

bgsB contributes to virulence during bacteremia in mice Previous experiments with a bgsA deletion mutant in E. faecalis showed that it leads

to an attenuation of virulence in a mouse bacteremia model [5]. To assess whether cell membrane glycolipids or glycolipid anchoring of LTA is required for the pathogenesis of enterococcal infections, we employed the same model to investigate the bgsB mutant. As mentioned above, 12030 wild-type and respective mutants had comparable growth characteristics. For virulence studies, we infected BALB/c mice 6 – 8 weeks old by i.v. injection, sacrificed the animals after 3 days, and enumerated the viable bacteria. Pilot experiments indicated that, with a high inoculum of 2 × 109 bacteria, infected mice are bacteremic up to 4 days without succumbing to the infection. Compared to the wild type, mice infected with 12030ΔbgsB or 12030ΔbgsA cleared significantly Ponatinib in vitro more bacteria from the bloodstream (Figure 6). No difference in virulence between 12030ΔbgsB and 12030ΔbgsA was detected in this model. Figure 6 Virulence of E. faecalis Δ bgsB in a mouse bacteremia model. Female BALB/c mice 6-8 weeks old were infected via the tail vein with stationary-phase E. faecalis strains (2.0 × 109 cfu). After 72 h mice were sacrificed and bacterial counts in the blood were enumerated. Data represent the individual bacterial counts and the geometric mean. ** P < 0.01, *** P < 0.001, Dunn’s multiple comparison test. The lower limit of detection of the assay was 10 CFU/ml blood.

The structural similarity of SscA to SycD made this protein a logical candidate. To test this hypothesis we immunoprecipitated SscA-FLAG from bacterial cells and

analyzed the co-precipitated proteins by Western blot learn more with anti-SseC antiserum. SseC was pulled down only in the Salmonella strain expressing SscA-FLAG and not from control lysates generated from untagged wild type cells (Figure 2A). To verify this interaction, we performed a reciprocal co-IP by pulling down SseC-FLAG and showing co-precipitation of SscA-His6 in the eluted protein fraction (Figure 2B). To examine the specificity of the SscA-SseC interaction, we tested whether SscA-FLAG could immunoprecipitate other members of the translocon apparatus, including SseB and SseD, which it did not (Figure 2C). These data indicated that SscA interacted with SseC, but not the other translocon proteins. Figure 2 Selleck SAHA HDAC SscA interacts with the translocon protein SseC. (A) Wild type Salmonella (left panels) and a strain carrying a plasmid expressing SscA-FLAG (right panels) were grown in

LPM minimal medium, lysed and subjected to immunoprecipitation with anti-FLAG antibody. Immunoprecipated proteins were probed by Western blot with anti-SseC antiserum and anti-FLAG antibody. (B) A reciprocal immunoprecipitation to that shown in part A was performed with a strain expressing SscA-His6 and a strain expressing both SscA-His6 and SseC-FLAG as indicated. SseC-FLAG was immunoprecipitated and proteins were blotted using

anti-His and anti-FLAG antibodies. (C) SscA-FLAG does not immunoprecipitate the SseB or SseD translocon proteins. The specificity of the SscA-SseC interaction was tested by probing SscA-FLAG immunoprecipitates with antibodies raised against SseD and SseB, neither of which was detectable in the final eluted protein fraction. Each immunoprecipitation experiment was repeated three times with similar results. SscA is necessary for secretion of SseC To determine Carbachol if the interaction between SscA and SseC was necessary for SseC secretion, we performed an in vitro secretion assay using wild type and ΔsscA under conditions that activate expression and activity of the SPI-2 T3SS. The secreted protein fraction from the culture supernatant of both wild type S. Typhimurium and ΔsscA was immunoblotted for the translocon proteins SseB, SseC, and SseD using specific antisera. The sscA mutant failed to secrete SseC as this protein was absent from the secreted protein fraction despite abundant levels in the bacterial cytoplasmic fraction (Figure 3A). SseC was detected in both the secreted protein and cytoplasmic fractions from wild type Salmonella and deletion of sscA had no demonstrable effect on the secretion of SseB or SseD (Figure 3A). To verify this phenotype, we complemented the ΔsscA mutant by transforming it with a plasmid to restore sscA expression.

7%) 94 (21.1%) P = 1.000 Number of adverse event 48 108   Number of patients with serious adverse events 21 (11.4%) 78 (17.5%) P = 0.070 Number of serious adverse events 26 88   Cardiac disorders 2 (1.1%) 3 (0.7%) P = 0.633 Gastrointestinal disorders 13 (7.1%) 3 (0.7%) P < 0.001  Epigastric pain 2 (1.1%) 0 (0.0%) P = 0.085  Constipation 3 (1.6%) 1 (0.2%) P = 0.078  Gastritis 3 (1.6%) 0 (0.0%) P = 0.025 General disorders and administration site conditions 3 (1.6%) 7 (1.6%) P = 1.000  Death 1 (0.5%)

7 (1.6%) P = 0.448 Infections and infestations 3 (1.6%) 9 (2.0%) P = 1.000  Pneumonia 1 (0.5%) 6 (1.3%) P = 0.680 Injury, poisoning and procedural complications 11 (6.0%) 60 (13.5%) P = 0.006  Hip fracture 3 (1.6%) 34 (7.6%) P = 0.002  Radius fracture 2 (1.1%) 1 (0.2%) P = 0.206  Spinal compression fracture 2 (1.1%)

9 (2.0%) click here P = 0.523 Musculoskeletal and connective tissue disorders 3(1.6%) 3 (0.7%) P = 0.365 Nervous system disorders 4 (2.2%) 4 (0.9%) P = 0.241  Dementia 2 (1.1%) 0 (0.0%) P = 0.085 Discussion In this study, the incidence of unaffected side hip fracture was compared between Japanese female osteoporosis patients who were followed-up after surgery for hip fracture with or without risedronate treatment. The incidence of unaffected side hip fracture was significantly lower in the risedronate group than the control group, suggesting a preventive effect of risedronate on hip Akt inhibitor fracture in these high-risk patients. According to recent reports [21, 22], the incidence of hip fracture is decreasing in Europe and the USA. However, it is anticipated that the worldwide incidence of hip fracture will continue to increase considering the aging of the population. For example, another study [23] has shown that the incidence of hip fracture is still increasing in Japan. Taking the speed of population aging into consideration, prevention of hip fracture is an urgent issue for Japanese health policy. There have only been two large-scale clinical studies with the primary endpoint of hip fracture, i.e., the HIP study [14] and the HORIZON study evaluating the effect of zoledronate [24], and both were placebo-controlled Abiraterone studies. Although there is sufficient evidence of a preventive

effect on hip fracture for various drugs, adequate information is not available about their relative efficacy and safety [16]. This study showed that risedronate can prevent new hip fractures in patients with a history of hip fracture, i.e., a high-risk population. It provides useful information for determining the management of osteoporosis. A subgroup analysis of patients with osteoporosis aged 70 years or older [15] from the HIP study evaluated the efficacy of risedronate for preventing hip fracture [14] and demonstrated that the 36-month incidence of hip fracture was 7.4% in the placebo group versus 3.8% in the risedronate group, with the relative risk being 0.54. In the present study, the 36-month incidence of unaffected side hip fracture was 13.