The drift of these parameters might bring out the variation of luciferase activity and, consequently, affect the application of bioreporters in detection of samples from natural aquatic environments.

To determine the application range of bioreporter selleck compound Palr0397-luxAB, we studied the influence of initial inoculum density and concentrations of nitrogen, phosphorus, Co2+, Mn2+, Zn2+, and Cu2+ on luciferase activity of the bioreporter under laboratory conditions in Fraquil medium with 10, 100, and 1000 nM Fe3+. The bioreporter cells were incubated for 12 h under the growth conditions described previously prior to bioluminescence measurement. Previous research revealed that high biomass of bioreporters (e.g. 107 cells mL−1)

could be used to increase bioreporter signal intensity (Van Der Meer et al., 2004). However, owing to the high levels of various organic chelants (Powell & Wilson-Finelli, 2003a ,b) and slow kinetics of reaction (Hudson & Morel, 1990), the concentration of dissolved iron is very low in some freshwaters (Nriagu et al., 1996; Sterner et al., 2004; Porta et al., 2005). The use of high biomass was likely to result in a bulk depletion of bioavailable iron and affect the practical assessment of iron bioavailability. With the increase in cell inoculum density (from 0.02 OD730 nm to 0.11 OD730 nm), luciferase activity of bioreporter Palr0397-luxAB increased firstly and then decreased (Fig. 2). A large consumption of bioavailable

PTC124 supplier Erastin molecular weight iron would promote the biosynthesis of siderophores to complex Fe3+ into cells (Ferguson & Deisenhofer, 2002; Wandersman & Delepelaire, 2004), which led to the increase in luciferase activity as cell numbers increased. Under higher Fe3+ concentrations (e.g. 100 or 1000 nM), the increase in siderophores because of the increased cell number could accelerate Fe3+ transport so as to rapidly enhance iron bioavailability, which might inversely suppress the use of iron to reduce luciferase activities of the bioreporter. At lower Fe3+ concentrations (e.g. 10 nM), when the cell numbers reached a high level, huge depletion of iron by excessive algal cells might affect the normal function of cells, thus inhibiting luciferase activity. Therefore, an initial inoculum density of OD730 nm = 0.06 was appropriate for the detection of bioavailable iron in water samples by bioreporter Palr0397-luxAB. The concentrations of nitrogen (N) and phosphorus (P) are greatly different in freshwaters. For example, the concentrations of total nitrogen (TN) and total phosphorus (TP) are 13.6–42.4 and 0.16–0.28 μM in Lake Erie (Charlton & Milne, 2004; DeBruyn et al., 2004). By contrast, the concentrations of TN and TP in Taihu, Chaohu, and Dianchi lakes of China, respectively, are 116.4–460.7 and 0.74–12.52 μM, 67.9–274.3 and 2.58–13.55 μM, and 214.3–1071.4 and 4.19–45.16 μM (Wang & Chen, 2009; Xu et al., 2010; Li & Xiao, 2011; Wilhelm et al., 2011).

In Turkey where diarrheagenic Escherichia coli are the major pathogens,4,5 the rate of protection against TD with rifaximin observed in this study (67%) was similar to that observed in a prior study by DuPont and colleagues6 among student

travelers to Mexico. The design of this study is unique from previous rifaximin prophylaxis trials because of the higher rifaximin daily dose (1,100 mg) administered. A safe and effective QD dosing regimen of rifaximin would be more convenient and potentially more cost effective versus a twice daily (BID) or three times daily (TID) dosing regimen. Although unclear, one wonders if a higher QD rifaximin dose of 1,100 mg might also have a residual protective impact seen with more frequent daily dosing regimen at lower rifaximin doses (eg, 200 mg BID or TID). Alternatively, QD scheduling at any dose may not be as effective as BID dosing given the possibility of a therapeutic trough with QD dosing, although in the DuPont and Selleckchem GKT137831 colleagues6 study, efficacy was observed with rifaximin 200 mg QD dosing. This study has important limitations including inadequate power due to lower than anticipated attack rate, limited microbiological outcomes, nonsequential treatment allocation, as well as issues of adherence ascertainment and to a lesser extent daily diary completion among enrollees. Despite these deficiencies, there was no discernable effect of the nonsequential treatment allocation on primary outcomes, although

such an effect cannot be ruled out. Furthermore, restricting

analysis to those for whom adequate this website adherence and outcome ascertainment could be assessed resulted in no appreciable change in the primary outcome with an estimated protective efficacy 71% (−34% to 94%; Fisher’s exact p = 0.14). Given the potential harms of long-term daily antibiotics in a population at risk for trauma-associated infections (including enteric trauma) and impact on individual and community microbiomes, it is uncertain that antimicrobial chemoprophylaxis would offer a practicable solution during most extended military deployments (which historically have averaged about 3–6 mo). However, eltoprazine there are a number of relevant settings including port visits, in special operations forces, or in the initial phase of deployment settings where risk of TD is highest and the consequences of heat injury are frequent, where chemoprophylaxis may offer an acceptable solution. Further studies to explore the efficacy and safety of TD chemoprophylaxis in these populations and settings are warranted. This study was supported by Salix Pharmaceuticals under a cooperative research and development agreement, and the Department of Defense Military Infectious Disease Research Program (Fort Detrick, MD, USA) under work unit no. 6000.RAD1.D.E0301. One or more authors of this article are military service members (or employees of the US Government). This work was prepared as part of official duties.

However, the patient did not respond Ipilimumab purchase to this treatment and fell into acute respiratory distress syndrome (Figure 1B) as early as 4 hours after we started therapy, and was sustained on a ventilator in the intensive care unit. At the time of entry into the intensive care unit, PaO2/FIO2 was 107, CK and CK-MB were within normal range, and BNP was 29.8 pg/mL. Echocardiography showed normal left ventricular function, normal wall movement,

and no dilatation of the inferior vena cava diameter. Because he did not present any respiratory symptoms such as cough and sputum, we were not able to collect a sputum sample for a bacterial culture. Blood samples obtained at the time of admission were examined for dengue, leptospirosis, and rickettsiosis at the National Institute for Infectious Diseases (NIID). On the third day of admission, we received an interim report from the NIID

that Rickettsia 17 kDa antigen[3] and citrate synthase gene[7, 8] (gltA) were detected in nested-PCR analysis, whereas Orientia tsutsugamushi (56 kDa)[9] was not. Considering the possibility of both typhus and spotted fever bio-groups, we stopped ceftriaxone and switched to ciprofloxacin injections (200 mg twice a day, dosage adjusted for renal dysfunction). His Trichostatin A chemical structure general and respiratory conditions gradually improved, and the patient was extubated on the sixth day of admission. Thereafter, he was treated with oral minocycline (100 mg twice a day) alone for 14 days. Finally, the sequences of two rickettsial genes, 17 kDa antigen (434 bp) and gltA (381 bp), detected by nested-PCR were identified as Rickettsia typhi Wilmington (NC006142) with 100% homology, whereas the PCR findings for dengue virus and Leptospira were negative, as were findings for the NS-1 antigen of the dengue O-methylated flavonoid virus, the anti-dengue virus specific-IgM antibody, and anti-leptospiral antibodies against 15 serovars, as shown in microscopic

agglutination test results. Unfortunately, we did not store the patient’s serum collected during the recovery phase and did not evaluate serological test results to confirm the diagnosis of murine typhus. However, we carefully performed nested-PCR for increased sensitivity, and targeted multiple gene fragments and sequencing. These results were considered to be reliable for the diagnosis of murine typhus. When febrile patients with a recent travel history are examined, it is important to consider malaria, dengue, mononucleosis, rickettsiosis, and typhoid/paratyphoid, whereas malaria, in particular, should be differentiated because of the high risk of mortality.

, 2008). Because expression of the sdrP gene was also enhanced by other stresses, cross-protection may occur via SdrP in T. thermophilus HB8. We wish to thank Keiko Sakamoto for the RT-PCR analysis. We also thank Noriko Nakagawa, Aiko Kashihara, Emi Ishido-Nakai, Miwa Ohmori, Kenji Fukui,

Takushi Ooga, Toshiko Miyazaki, and Keiko Sakamoto for their excellent support in the GeneChip analysis, and Kazuko Agari for the excellent support with preparation of the templates for the in vitro transcription assays. Fig. S1. Expression pattern analysis using DNA microarray data. Fig. S2. Identification of the transcriptional start site. Table S1. GEO accession numbers and experimental conditions for the DNA microarray dataset. Table S2. Oligonucleotides used in selleck products this study. Table S3. Number of genes correlated with sdrP

gene in each COGs category. Table S4. Genes exhibiting Spearman’s correlation coefficients, as to the sdrP gene, of ≥0.50. Table S5. Genes exhibiting Spearman’s correlation coefficients as to the sdrP gene, of ≤-0.50. Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. “
“Four bacterial strains capable of growing in the presence of tannic acid as sole carbon and energy source were isolated from olive mill waste mixtures. 16S rRNA gene Crizotinib sequencing assigned them to the genus Klebsiella. The most efficient strain, Klebsiella sp. strain C2A, was able to degrade 3.5 g L−1 tannic acid within 35 h with synthesizing gallic acid as main product. The capability of Klebsiella sp. strain C2A to produce tannase was evidenced at high concentrations of tannic acid up to 50 g L−1. The bacteria adapted to the toxicity of tannic acids by an increase in the membrane lipid fatty acids degree of saturation, especially in the presence of concentrations higher than 20 g L−1. The highly tolerant and adaptable bacterial strain characterized in this study Avelestat (AZD9668) could be used in bioremediation processes of

wastes rich in polyphenols such as those derived from olive mills, winery or tanneries. “
“The present study was conducted to test the ability of probiotic lactobacilli to alter age-related immunosenescence in host animals. Senescence-accelerated mouse prone 1 mice were orally fed heat-killed Lactobacillus gasseriTMC0356 (TMC0356) for 4 and 8 weeks at dosages of 10 mg day−1 after a 16-week period of prefeeding with a standard diet. After 4 and 8 weeks of TMC0356 intervention, splenic activation of natural killer (NK) cells and mRNA expression of cytokines and other immune molecules in the lungs were analysed. After 4 and 8 weeks, splenic NK cell activities were significantly higher in the TMC0356-fed mice compared with control mice (P < 0.05).

Communication between mother cell and isolated forespore involves a specialised connection system that allows nurturing of the forespore and continued macromolecular synthesis, required to finalise spore maturation. Here,

we review current understanding of this feeding channel formed by a forespore protein, SpoIIQ, and a mother cell protein, SpoIIIAH, in the GSK3 inhibitor model organism Bacillus subtilis and the important human pathogen Clostridium difficile. We also analyse the presence of this channel across endospore-forming bacteria and highlight the main questions still remaining. “
“Streptococcus suis 2 (SS2) is a zoonotic pathogen that can participate in biofilm formation to survive in hostile environments. In this study, virulent SS2 strains HA9801 and ZY05719 displayed increased biofilm formation compared with SS2 avirulent strain T15. In addition, a 58% reduction in adherence to HEp-2 cells was observed

for HA9801 biofilm cells, compared with HA9801 planktonic cells. The 50% lethal dose (LD50) of biofilm cells was 40-fold greater than that of planktonic cells. Quantification of expression levels of known virulence genes by real-time PCR revealed that the transcription levels of the gdh, cps2 and mrp genes in biofilm cells were downregulated, while the sly and gapdh genes were upregulated. HA9801 biofilm and planktonic vaccines LY2835219 mouse provided 60% and 46% protection, respectively, when challenged with 50 times the LD50 of the HA9801 strain. These results suggest a possible connection between virulence and the ability of biofilm formation; cell adhesion, transcription levels and virulence properties are different between biofilm cells and planktonic cells. Furthermore, this work offers a novel insight into bacterium infection mechanisms, which suggests that a virulent strain may be able to decrease its virulence

by forming a biofilm so that it can achieve persistent infection in vivo. Streptococcus suis (SS) is a major pathogen of pigs worldwide and causes septicemia, meningitis, and endocarditis (Gottschalk et al., 1999), which colonizes the respiratory tract, particularly mafosfamide the tonsils and nasal cavities, as well as the genitals (Gottschalk et al., 2010). Among the 35 different serotypes, SS2 is known to be the most virulent and frequently isolated serotype (Principi & Marchisio, 1999). In addition, SS is believed to be a normal inhabitant of a variety of ruminants (Staats et al., 1997). The pig carrier rate is nearly 100%; however, mortality rates can reach 20% (Cloutier et al., 2003). SS binds to extracellular matrix proteins, including fibronectin and collagen (Esgleas et al., 2005), as well as to endothelial and epithelial cells (Charland et al., 2000; Benga et al., 2004), but the mechanisms by which the bacterium invades, infects, and incubates the host are unclear.

3E8.D10 (Affinity BioReagents Co.) may not be completely overlapped with Autophagy inhibitor molecular weight FimH-binding site on the ATP synthase β-subunit. Another possibility is that ATP synthase β-subunit may be one of several mannose-insensitive binding targets on HBMEC for fim+E. coli K1. In summary, type 1 fim+E. coli K1 binds to HBMEC in both mannose-sensitive and -insensitive manner. We have identified that CD48 is the mannose-containing HBMEC surface receptor

interacting with FimH (Khan et al., 2007). In the present study, the mannose-insensitive receptors for FimH on the surface of HBMEC were identified, which include ATP synthase β-subunit. The mannose-insensitive FimH binding may contribute to E. coli K1 binding to HBMEC in the mannose moiety-rich environment such as the bloodstream, where meningitis-causing E. coli K1 interacts MS-275 in vivo with the blood–brain barrier to penetrate into the central nervous system. Additional studies are needed to further elucidate the role of mannose-insensitive HBMEC binding in the pathogenesis of E. coli K1 meningitis. This work was supported in part by the NIH grants NS 26310 and AI 47225. Fig. S1. Immunofluorescence microscopy for the localization of ATP synthase β-subunit and

β-actin in HBMEC. Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. “
“Bacteriophage Mu was the first transposable phage to be discovered and still serves as the model for a large

family of related transposable phages and prophages. The Mu genome sequence Metformin molecular weight is known (NC-000929.1 GI:9633494), but not all of the genes have been assigned to the ORFs in the genome sequence. For this paper, we have sequenced an approximately 3-kb DNA region containing four predicted ORFs, Mup35–Mup38, from lysogens containing amber mutant prophages defective in either the J or the K gene. Amber mutations in prophages with J gene mutations mapped to the Mup36 ORF, and those in the K gene were found in Mup37, identifying the ORFs corresponding to these genes. Bacteriophages have served as excellent model systems for the study of regulation of gene expression, DNA replication, and the stepwise assembly of protein subunits into complex macromolecular structures that package and protect the phage nucleic acid genome in mature phage particles (Toussaint et al., 1994; Rao & Feiss, 2008; Hamdan & Richardson, 2009). Phage Mu was discovered in 1963 and named Mu (for mutator) for its unprecedented ability to cause mutations in Escherichia coli genes upon lysogenization (Taylor, 1963). Such mutations are caused by integration of the Mu genome into host genes, at essentially random locations in the host genome (Taylor, 1963).

, 2009). Enolase is responsible for the reversible catalysis of 2-phospho-d-glycerate

(2PGA) and phosphoenolpyruvate (PEP) in glycolysis and gluconeogenesis (Nurmohamed et al., 2010). The enzyme is highly conserved in archaea, bacteria, and eukaryotes with similar catalytic properties (Nurmohamed et al., 2010). In E. coli, it is associated with RNaseE in a multienzyme complex RNA degradososme (Nurmohamed et al., 2010). Aconitases are known to be crucial enzymes GSK126 in the tricarboxylic acid (TCA) cycle (Kozíol et al., 2009) and are induced in response to higher energy requirement of the cell (Martínez et al., 2007). It is possible that to survive under heat-stressed condition, TSB-6 generates higher metabolic activity, and the concomitant higher energy requirement leads to the induction of enzymes such as aconitate

hydratase. Several chaperonins Trichostatin A price have been shown to be upregulated in bacteria in response to chromium (VI) or heat shock (Kiliç et al., 2010). Besides their role in protein folding, some chaperonins possess reductase activity that enables them to protect the bacteria against oxidative damage (Kiliç et al., 2010). Chaperones have also been found to be involved in biogenesis of several enzymes by cofactor insertion (Ribbe & Burgess, 2001; Stevens et al., 2005; Vergnes et al., 2006). It may be interesting to investigate whether chaperonins participate in the biogenesis of a functional chromate reductase. We express our deep gratitude to Binayak Dutta-Roy, who has been the main inspiration behind this work. We also thank Subrata Kundu and Suparna Ghosh of Bose Institute for technical help. This work was supported by a grant from the Department of Science and Technology,

Government of India (SR/SO/BB-33/2003), with a fellowship to S.C.P. “
“Samsung Advanced Institute of Technology, Yongin, Gyeonggi, Korea The function of whcB, one of the four whiB homologues of Corynebacterium glutamicum, was assessed. Cells carrying the P180-whcB clone, Pyruvate dehydrogenase lipoamide kinase isozyme 1 and thus overexpressing the whcB gene, showed retarded growth, probably due to increased sensitivity to oxidants, whereas cells lacking whcB (ΔwhcB) did not. However, growth retardation was not observed in cells with additionally whcE deleted. Furthermore, the ΔwhcE phenotype, characterized by slow growth and sensitivity to oxidants, was reversed in cells carrying P180-whcB. Like the whcE gene, which is also known as a whiB homologue, the whcB gene was preferentially expressed in stationary phase. Determination of the genes under regulation of whcB using two-dimensional polyacrylamide gel electrophoresis identified several genes involved in electron transfer reactions that were regulated in cells carrying P180-whcB. Collectively, these findings indicate that whcB function requires whcE.

However, our design is similar to those of the two other contemporary studies that report rates of SAB among HIV-infected individuals [5,24]. We do not have information on the use of prophylaxis for Pneumocystis jirovecii and atypical mycobacterial disease or the treatment of tuberculosis. Antimicrobials with activity against P. jirovecii and mycobacteria have antibacterial activity and have been shown to reduce rates of invasive bacterial disease [33–35]. Use of such drugs would lead to an underestimation of IRs in individuals with low CD4 cell counts. However, just 6% of the observation time was accounted for by HIV-infected individuals with CD4 counts

<100 cells/μL. Surveillance bias may have led to an overestimation

of IRs among HIV-infected individuals because find more physicians are likely to have a lower threshold for hospital admission and work-up of HIV-infected individuals, who have closer health care contact than the general population. click here If an individual was identified in the DHCS they were considered to be infected with HIV. If an individual was not present in the DHCS, they were considered to be HIV uninfected. This is not necessarily a safe assumption, as it is estimated that 1000 individuals are infected but not yet diagnosed with HIV and thus unaware of their infection. This number has been reached using back calculation for the period up to 1995, and for the period from 1996 onwards based on the assumption of a constant HIV incidence in Denmark [36]. In addition to regular HIV testing of IDUs, HIV testing could prove beneficial in younger adults who are not IDUs and who present with CA SAB. We found that the incidence of SAB in HIV-infected individuals declined during Adenylyl cyclase the study period, but remained higher than that in HIV-uninfected individuals. The burden of SAB was disparately distributed among groups

of HIV-infected individuals so that IDUs had a 20-fold higher IR of SAB compared with MSM in the late time period (2003-2007). Immunodeficiency was the strongest predictor of SAB among HIV-infected individuals, although the underlying mechanisms are likely to differ among HIV transmission groups. IDU, nonsuppressed HIV RNA and lack of HAART also predicted SAB. The authors thank the staff at the participating clinical departments and the clinical microbiological laboratories for their contributions, continuous support and enthusiasm. Centres in the Danish HIV Cohort Study are as follows: Departments of Infectious Diseases at Copenhagen University Hospitals, Rigshospitalet (J. Gerstoft and N. Obel) and Hvidovre (G. Kronborg), Odense University Hospital (C. Pedersen), Aarhus University Hospitals, Skejby (C. S. Larsen) and Aalborg (G. Pedersen), Herning Hospital (A. L. Laursen), Helsingør Hospital (L. Nielsen) and Kolding Hospital (J. Jensen). Author contributions: MVL, ZBH and TB conceived and designed the experiments.

However, our design is similar to those of the two other contemporary studies that report rates of SAB among HIV-infected individuals [5,24]. We do not have information on the use of prophylaxis for Pneumocystis jirovecii and atypical mycobacterial disease or the treatment of tuberculosis. Antimicrobials with activity against P. jirovecii and mycobacteria have antibacterial activity and have been shown to reduce rates of invasive bacterial disease [33–35]. Use of such drugs would lead to an underestimation of IRs in individuals with low CD4 cell counts. However, just 6% of the observation time was accounted for by HIV-infected individuals with CD4 counts

<100 cells/μL. Surveillance bias may have led to an overestimation

of IRs among HIV-infected individuals because selleck physicians are likely to have a lower threshold for hospital admission and work-up of HIV-infected individuals, who have closer health care contact than the general population. Palbociclib in vivo If an individual was identified in the DHCS they were considered to be infected with HIV. If an individual was not present in the DHCS, they were considered to be HIV uninfected. This is not necessarily a safe assumption, as it is estimated that 1000 individuals are infected but not yet diagnosed with HIV and thus unaware of their infection. This number has been reached using back calculation for the period up to 1995, and for the period from 1996 onwards based on the assumption of a constant HIV incidence in Denmark [36]. In addition to regular HIV testing of IDUs, HIV testing could prove beneficial in younger adults who are not IDUs and who present with CA SAB. We found that the incidence of SAB in HIV-infected individuals declined during why the study period, but remained higher than that in HIV-uninfected individuals. The burden of SAB was disparately distributed among groups

of HIV-infected individuals so that IDUs had a 20-fold higher IR of SAB compared with MSM in the late time period (2003-2007). Immunodeficiency was the strongest predictor of SAB among HIV-infected individuals, although the underlying mechanisms are likely to differ among HIV transmission groups. IDU, nonsuppressed HIV RNA and lack of HAART also predicted SAB. The authors thank the staff at the participating clinical departments and the clinical microbiological laboratories for their contributions, continuous support and enthusiasm. Centres in the Danish HIV Cohort Study are as follows: Departments of Infectious Diseases at Copenhagen University Hospitals, Rigshospitalet (J. Gerstoft and N. Obel) and Hvidovre (G. Kronborg), Odense University Hospital (C. Pedersen), Aarhus University Hospitals, Skejby (C. S. Larsen) and Aalborg (G. Pedersen), Herning Hospital (A. L. Laursen), Helsingør Hospital (L. Nielsen) and Kolding Hospital (J. Jensen). Author contributions: MVL, ZBH and TB conceived and designed the experiments.

However, our design is similar to those of the two other contemporary studies that report rates of SAB among HIV-infected individuals [5,24]. We do not have information on the use of prophylaxis for Pneumocystis jirovecii and atypical mycobacterial disease or the treatment of tuberculosis. Antimicrobials with activity against P. jirovecii and mycobacteria have antibacterial activity and have been shown to reduce rates of invasive bacterial disease [33–35]. Use of such drugs would lead to an underestimation of IRs in individuals with low CD4 cell counts. However, just 6% of the observation time was accounted for by HIV-infected individuals with CD4 counts

<100 cells/μL. Surveillance bias may have led to an overestimation

of IRs among HIV-infected individuals because Trametinib in vivo physicians are likely to have a lower threshold for hospital admission and work-up of HIV-infected individuals, who have closer health care contact than the general population. Idelalisib research buy If an individual was identified in the DHCS they were considered to be infected with HIV. If an individual was not present in the DHCS, they were considered to be HIV uninfected. This is not necessarily a safe assumption, as it is estimated that 1000 individuals are infected but not yet diagnosed with HIV and thus unaware of their infection. This number has been reached using back calculation for the period up to 1995, and for the period from 1996 onwards based on the assumption of a constant HIV incidence in Denmark [36]. In addition to regular HIV testing of IDUs, HIV testing could prove beneficial in younger adults who are not IDUs and who present with CA SAB. We found that the incidence of SAB in HIV-infected individuals declined during Urease the study period, but remained higher than that in HIV-uninfected individuals. The burden of SAB was disparately distributed among groups

of HIV-infected individuals so that IDUs had a 20-fold higher IR of SAB compared with MSM in the late time period (2003-2007). Immunodeficiency was the strongest predictor of SAB among HIV-infected individuals, although the underlying mechanisms are likely to differ among HIV transmission groups. IDU, nonsuppressed HIV RNA and lack of HAART also predicted SAB. The authors thank the staff at the participating clinical departments and the clinical microbiological laboratories for their contributions, continuous support and enthusiasm. Centres in the Danish HIV Cohort Study are as follows: Departments of Infectious Diseases at Copenhagen University Hospitals, Rigshospitalet (J. Gerstoft and N. Obel) and Hvidovre (G. Kronborg), Odense University Hospital (C. Pedersen), Aarhus University Hospitals, Skejby (C. S. Larsen) and Aalborg (G. Pedersen), Herning Hospital (A. L. Laursen), Helsingør Hospital (L. Nielsen) and Kolding Hospital (J. Jensen). Author contributions: MVL, ZBH and TB conceived and designed the experiments.