Exclusion criteria included: chronic hepatitis B [hepatitis B vir

Exclusion criteria included: chronic hepatitis B [hepatitis B virus surface antigen (HBsAg)-positive at screening]; hepatitis C virus infection (RNA positive) that was likely

to require treatment within the next 12 months, or with historical evidence learn more of significant fibrosis, cirrhosis and/or hepatic decompensation; a new AIDS-defining condition diagnosed within 35 days prior to the first dose of the study drug; presence of Q151M or 69 insertion mutations in HIV-1 reverse transcriptase at screening; current treatment with zalcitabine; a regimen comprised only of three nucleoside/nucleotide reverse transcriptase inhibitors. Women of childbearing potential were required to have a negative pregnancy test and adequate contraception was required of all patients. Patients were randomly assigned

in a 1:1:1 NVP-AUY922 ratio to receive 600 mg ATC twice daily (bid), 800 mg ATC bid or 150 mg 3TC bid, taken orally, plus matching placebos. Double dummy dosing was used in this study. 3TC was given as over-encapsulated 150 mg tablets and patients in the two ATC arms received a placebo capsule matching the 3TC capsule in size, colour and approximate weight. Patients in the 3TC arm received placebo capsules matching the ATC capsules. A centralized randomization scheme was used and randomization was stratified by the number of TAMs present at screening (fewer than three

TAMs or at least three TAMs/K65R), according to the study protocol. Throughout the study, both patients and investigators were blinded to the treatment allocation. The study design is shown in Figure 1. The study was divided into the following treatment periods. On day 0, patients stopped their existing 3TC or FTC treatment and commenced blinded therapy. Montelukast Sodium No other changes to background ART were permitted during this period. On day 21, the background ART could be optimized to contain at least two agents expected to provide activity based on genotype at screening, and blinded therapy continued to week 24. Any approved ART could be used with the exceptions of 3TC, FTC and zalcitabine. After week 24, patients ceased randomized therapy and were offered open-label ATC (800 mg bid) to week 48. After day 21, re-optimization of background ART for lack of response/virological failure was permitted and access to open-label ATC 800 mg bid was provided upon meeting failure criteria (a confirmed<0.5 log10 reduction in HIV RNA from baseline or a confirmed >1 log10 increase in HIV RNA from nadir). The choice of ART for this subsequent regimen was based on genotype at screening or at subsequent evaluations.

At a time when there were two main models for revalidation: the m

At a time when there were two main models for revalidation: the medical one, using appraisals, and the dental model, focussing on CPD, the GPhC commissioned research to evaluate the utility of appraisals and alternative sources of evidence in pharmacy. This involved qualitative interviews and surveys with stakeholders in community, hospital, pharmaceutical industry, and academia, each from the perspective of registrants and those who may play a role in revalidation, particularly employers and indeed the regulator.(8-12) With pharmacy professionals working in a variety of sectors, Selleck AZD2281 with most in direct patient

contact, it became clear that the options and requirements for different professionals in different sectors and organisations varied. Appraisals were common in the managed sector, but some (e.g. owners, locums, portfolio workers) were not covered. Appraisals may not be fit-for-purpose, as focus was organisational (business targets in community and industry; teaching/research in academia). Other than in NHS sectors, appraisals NSC 683864 molecular weight did not address competence or fitness-to-practise, and were often conducted by non-pharmacists. Concerns over independence of assessment and the role of employers were raised. It is also worth

noting that revalidation is not just for pharmacists but also pharmacy technicians, which leads onto the next ‘big question’. At a time of debate in the profession about supervision, and the start of a programme to rebalance medicines legislation and pharmacy regulation, Pharmacy Research UK commissioned a study entitled ‘supervision in community pharmacy’. Its aim was to explore the role of skill mix and effective role delegation to enable pharmacists’ increasing clinical, patient-centred roles. A method called nominal group technique was used to identify which pharmacy activities could or could not be safely performed by appropriately trained support staff during a pharmacist’s

PtdIns(3,4)P2 2-hour absence. Views were explored in qualitative discussions, followed by a large scale survey of pharmacists and pharmacy technicians in community and hospital.(13;14) Safe, borderline and unsafe activities were identified, with borderline activities crucial for the flow of tasks involving more than one activity (e.g. cascade of dispensing). Community pharmacists were most reluctant to relinquish control, with trust in, and familiarity with, the team being important. Challenges underpinning effective delegation centred on clear roles, responsibilities and accountability, and quality of staff training and competence, with pharmacy technicians the most likely group to take on extended roles. My lecture will lay out the importance of research informing teaching and learning, policy, practice and regulation, illustrated through the context of big questions, the detail of addressing these and some of the key findings.

All subjects received pre-travel counseling and were provided ant

All subjects received pre-travel counseling and were provided antibiotics and antidiarrheals (loperamide) for use only if TD developed. The subjects were blinded and randomized to take two capsules of placebo or oral synbiotic (a combination of two probiotics and a prebiotic) called Agri-King Synbiotic (AKSB) beginning 3 days prior to departure, daily while traveling, and for 7 days after return. All subjects kept symptom and medication Selleck Mitomycin C diaries and submitted a stool sample for pathogen carriage

within 7 days of return. The study was powered to detect a 50% reduction in the incidence of TD. Of the 196 adults (over 18 years of age) enrolled in the study, 54.3% were female and 80.9% were younger than 60 years. The study randomized 94 people to the AKSB arm and 102 to placebo. The incidence of TD was 54.5% in the overall group with 55.3% in the AKSB arm and 53.9% in the placebo (p = 0.8864). Among the subjects who experienced

diarrhea (n = 107) there was no significant difference in the proportion of subjects that took antibiotics versus those that did not take antibiotics (35% vs 29%, p = 0.68). AKSB was safe with no difference in toxicity between the two arms. The prophylactic oral synbiotic was safe but did not reduce the risk of developing TD among travelers, nor did it decrease the duration of TD or the use of antibiotics when TD occurred. Travelers’ diarrhea (TD) is associated with significant morbidity and a decrease in quality of life for international travelers.[1] Symptoms of TD are usually self-limited and resolve within a week. 3-MA manufacturer MRIP It is estimated that 20% to 50% of people traveling to developing areas will develop TD.[2] TD is defined by more than three loose stools per day with or without associated symptoms of fever, nausea, or abdominal pain.[3] It is typically caused by bacterial pathogens such as enterotoxigenic Escherichia coli, enteroaggregative E coli, Campylobacter

species, Shigella species, or Salmonella species. Prevention of TD relies on food and water precautions. Primary prevention of TD using antimicrobials such as fluoroquinolones,[4] rifaximin,[5, 6] or non-antibiotic strategies such as bismuth subsalicylate (Pepto-Bismol)[7, 8] are effective but are typically reserved for high-risk populations, such as severely immunosuppressed patients. Use of these agents is also restricted owing to cost, emerging antimicrobial resistance, and dosing complexity (eg, bismuth subsalicylate is best taken as two tablets every 6 hours). Travelers are often provided with antimicrobials and loperamide to self-treat severe diarrhea, should it occur. Self-treatment of TD with antibiotics (often fluoroquinolones or azithromycin) reduces the duration of symptoms to 1 to 2 days.[9] However, with increasing travel and antimicrobial resistance, it is important to identify non-antimicrobial-based preventive strategies, such as probiotics, to prevent or treat TD.

Estimation of metabolite pools suggested that these phenotypes co

Estimation of metabolite pools suggested that these phenotypes could be the result of profound metabolic changes

in the ΔcymR mutant including an increase of the intracellular cysteine pool and hydrogen sulfide formation, as well as a depletion of branched-chain Selleck GPCR Compound Library amino acids. The sulfur-containing amino acid, cysteine, plays a major role in cellular physiology. Cysteine biosynthesis is the primary pathway for incorporating sulfur into cellular components. This amino acid is a precursor of methionine and also thiamine, biotin, lipoic acid, coenzyme A and coenzyme M, and is required for the biogenesis of [Fe–S] clusters. Cysteine residues are found in the catalytic site of several enzymes and aid protein folding and assembly by forming disulfide bonds. Moreover, proteins with active-site cysteines such as thioredoxin or cysteine-containing molecules such as glutathione, mycothiol, coenzyme A and bacillithiol play an important role in protecting cells against oxidative

stress (Masip et al., 2006; Newton et al., 2009). Several studies have shown that cysteine itself plays a role in bacterial sensitivity to oxidative stress (Hung et al., 2003; Park & Imlay, 2003; Hochgrafe et al., 2007). More generally, recent data reported the existence of links between cysteine metabolism and various stress stimuli such as peroxide (H2O2), superoxide, diamide, nitric oxide, thiol-reactive electrophiles and metal ions (Park & Imlay, 2003; Liebeke Tau-protein kinase et al., 2008;

Nguyen et al., 2009; Pother learn more et al., 2009). Two major cysteine biosynthetic pathways are present in Bacillus subtilis: the thiolation pathway, which requires sulfide, and the reverse trans-sulfuration pathway, which converts homocysteine to cysteine via a cystathionine intermediate (Soutourina & Martin-Verstraete, 2007). Homocysteine is synthesized from methionine, while sulfide is yielded mostly from the reduction of sulfate. Finally, thiosulfate or glutathione can also be used as cysteine precursors in this bacterium. Under environmentally oxidizing conditions, cysteine dimerizes to form the disulfide-linked cystine, which is generally the compound transported. Three uptake systems for cystine, two ABC transporters and a symporter, are present in B. subtilis (Burguière et al., 2004). Because of the reactivity of its SH group and its toxicity, the cysteine metabolism is tightly controlled. The CymR repressor has been identified recently as the master regulator of cysteine metabolism in B. subtilis and Staphylococcus aureus (Choi et al., 2006; Even et al., 2006; Soutourina et al., 2009). In B. subtilis, CymR negatively regulates the expression of genes encoding cystine transporters (tcyP and tcyJKLMN) or involved in cysteine synthesis (cysK and mccAB) or sulfonate assimilation (Even et al., 2006).

, 2003) In contrast, autophagic PCD is induced by the heterokary

, 2003). In contrast, autophagic PCD is induced by the heterokaryon incompatibility system of Podospora anserina (Pinan-Lucarréet al., 2003). Thus, the mechanism for PCD appears to vary among organisms rather than being consistent within a taxon. In previous research, we collected H. mompa isolates belonging to numerous kinds of mycelial compatibility groups (Ikeda et al., 2004). In this study, we performed cytological

analysis of mycelial incompatibility in H. mompa using light and transmission electron microscopy (TEM). The H. mompa isolates used were V18 (MAFF No. 305915), V670 (MAFF No. 328063). Cultures were maintained in Petri dishes on oatmeal agar (26 g L−1 oatmeal, 5 g L−1 sucrose, 15 g L−1 agar) at 4 °C until use. We paired H. mompa isolates (V18 vs. V670) on rectangular cellulose membranes (1 × 1.5 cm size) laid on water agar plates (15 g L−1 agar) or on 1/10-strength oatmeal Selumetinib molecular weight agar plates (2.6 g L−1 oatmeal, 5 g L−1 sucrose, 15 g L−1 agar) with or without 0.2% w/v activated charcoal (Wako, Osaka, Japan) in 50-mm-diameter Petri dishes (AS One, Osaka, Japan). We placed one mycelial plug on one of the short sides of the rectangle and the confronting mycelial plug at the opposite find more side, separated by 7.5 mm. After incubation of the cellulose membranes for 3 days at 25 °C, we transferred the plugs to 50-mm-diameter glass-bottomed culture dishes (MatTek,

Ashland, MA) that contained no growing medium and observed the hyphal contact zones with a fluorescence microscope (BIOREVO BZ-9000, Keyence, selleck Osaka, Japan). To evaluate the nature of the hyphal contact, we searched for hyphae that were in contact and for which both tips were visible in the field of view at of × 40 objective lens. We evaluated hyphal fusion on the basis

of whether the cell walls had merged. We tracked hyphae backwards from the zone of contact to clarify the origin of each hypha (i.e. which isolates produced it) to confirm that the hyphae represented reciprocal pairs rather than self-pairs. As some hyphae also extended vertically, we excluded the hyphal crossing in which one hypha passed over another hypha without hyphal contact; we judged this to occur when it was not possible to view both hyphae simultaneously in the same focal plane. We paired the H. mompa isolates (V18 vs. V18 or V18 vs. V670) on Aclar film (Nisshin EM, Tokyo, Japan) laid on a glass slide coated with 1/10-strength oatmeal agar medium and incubated at 25 °C for 4 days in 90-mm-diameter Petri dishes that included agar medium (15 g L−1 agar) to maintain moisture. The mycelia on the glass slide were first fixed with 2.5% glutaraldehyde (Nisshin EM) in 0.1 M phosphate-buffered saline (PBS), pH 7.4 at 4 °C overnight. The pieces were rinsed with PBS three times at the intervals of 10 min, and postfixed with 1% osmium tetroxide (Nisshin EM) in PBS at room temperature for 1 h.

, 2003) In contrast, autophagic PCD is induced by the heterokary

, 2003). In contrast, autophagic PCD is induced by the heterokaryon incompatibility system of Podospora anserina (Pinan-Lucarréet al., 2003). Thus, the mechanism for PCD appears to vary among organisms rather than being consistent within a taxon. In previous research, we collected H. mompa isolates belonging to numerous kinds of mycelial compatibility groups (Ikeda et al., 2004). In this study, we performed cytological

analysis of mycelial incompatibility in H. mompa using light and transmission electron microscopy (TEM). The H. mompa isolates used were V18 (MAFF No. 305915), V670 (MAFF No. 328063). Cultures were maintained in Petri dishes on oatmeal agar (26 g L−1 oatmeal, 5 g L−1 sucrose, 15 g L−1 agar) at 4 °C until use. We paired H. mompa isolates (V18 vs. V670) on rectangular cellulose membranes (1 × 1.5 cm size) laid on water agar plates (15 g L−1 agar) or on 1/10-strength oatmeal Dabrafenib order agar plates (2.6 g L−1 oatmeal, 5 g L−1 sucrose, 15 g L−1 agar) with or without 0.2% w/v activated charcoal (Wako, Osaka, Japan) in 50-mm-diameter Petri dishes (AS One, Osaka, Japan). We placed one mycelial plug on one of the short sides of the rectangle and the confronting mycelial plug at the opposite Erlotinib concentration side, separated by 7.5 mm. After incubation of the cellulose membranes for 3 days at 25 °C, we transferred the plugs to 50-mm-diameter glass-bottomed culture dishes (MatTek,

Ashland, MA) that contained no growing medium and observed the hyphal contact zones with a fluorescence microscope (BIOREVO BZ-9000, Keyence, Histidine ammonia-lyase Osaka, Japan). To evaluate the nature of the hyphal contact, we searched for hyphae that were in contact and for which both tips were visible in the field of view at of × 40 objective lens. We evaluated hyphal fusion on the basis

of whether the cell walls had merged. We tracked hyphae backwards from the zone of contact to clarify the origin of each hypha (i.e. which isolates produced it) to confirm that the hyphae represented reciprocal pairs rather than self-pairs. As some hyphae also extended vertically, we excluded the hyphal crossing in which one hypha passed over another hypha without hyphal contact; we judged this to occur when it was not possible to view both hyphae simultaneously in the same focal plane. We paired the H. mompa isolates (V18 vs. V18 or V18 vs. V670) on Aclar film (Nisshin EM, Tokyo, Japan) laid on a glass slide coated with 1/10-strength oatmeal agar medium and incubated at 25 °C for 4 days in 90-mm-diameter Petri dishes that included agar medium (15 g L−1 agar) to maintain moisture. The mycelia on the glass slide were first fixed with 2.5% glutaraldehyde (Nisshin EM) in 0.1 M phosphate-buffered saline (PBS), pH 7.4 at 4 °C overnight. The pieces were rinsed with PBS three times at the intervals of 10 min, and postfixed with 1% osmium tetroxide (Nisshin EM) in PBS at room temperature for 1 h.

A post hoc analysis demonstrated that patients with increased syn

A post hoc analysis demonstrated that patients with increased synovitis and who had failed only one biologic

had significantly improved ACR20 responses.[46] In a 24-week phase 2 trial of fostamatinib on background MTX, patient-reported outcomes of pain, disease activity, fatigue and physical function were improved in patients taking 100 mg twice daily.[47] However, recent phase 3 clinical trials have reported mixed results, prompting the manufacturers of fostamatinib to put further drug development trials on hold.[48] The past 20 years have seen significant advances in the treatment of RA. MTX led the way providing not only symptom control, Tacrolimus cell line but also the ability to alter disease progression. Over the past 10 years, biologic DMARDs have expanded on this success and offered an alternative to those unable to achieve positive outcomes with traditional synthetic DMARDs alone. Despite these triumphs there remains a need for safe and effective alternatives to the currently available RA therapies. Some patients who receive a biologic agent fail to achieve an adequate primary response and others experience a secondary loss of response. Further, biologics depend on an injectable route of administration, which is not appealing to a small subset of RA patients. Unfortunately, no advantage in drug cost has been achieved, as tofacitinib falls near the same price point as current biologic

therapies. Novel small-molecule pharmacologic agents, such as JAK and Syk inhibitors, have the potential to become an alternative to biologic drugs for some PD0332991 research buy patients with RA. Many clinical trials have demonstrated their efficacy in patients with inadequate Aldol condensation disease control from traditional non-biologic and biologic DMARDs. Longer-term studies will be crucial to understand better the adverse effects and overall safety profile of these drugs. None. None of the authors have any competing interests to declare. “
“To investigate MRI findings that may predict

unfavorable outcomes in the patients with neuro-Behçet’s disease. All consecutive patients referred from 2002 to 2009 to the Behçet Clinic at Nemazee Hospital, Shiraz, Iran, who fulfilled International Study Group criteria for Behçet’s disease and diagnosed as having neuro-Behçet’s disease, were enrolled into this study. Characteristics of initial brain MRI were studied in patients with different courses of neuro-Behçet’s disease. Initial MRIs of 58 patients (31 women) with a mean ± SD age of 38.9 ± 9.7 years were reviewed. Forty-nine (84%) patients had parenchymal and nine (16%) had non-parenchymal neuro-Behçet’s disease. Of those patients with parenchymal neuro-Behçet’s disease, 15 (31%) had monophasic, 13 (27%) polyphasic and 10 (20%) progressive courses; 11 (22%) had only headache attributed to Behçet’s disease. The most common sites of involvement in patients with parenchymal neuro-Behçet’s disease were periventricular and superficial cerebral white matter, midbrain and pons, respectively.

Until data are available, this preparation is not advised for thi

Until data are available, this preparation is not advised for this group. In the pre-HAART era, HIV-infected children responded poorly to HBV vaccine [73]. Post-HAART, a study evaluating the response to revaccination after immune recovery on antiretroviral therapy (ART) demonstrated that those with complete virological suppression at the time of revaccination achieved protective vaccine responses [74], however protective

responses were achieved less frequently in children under 2 years of age [75]. It is not currently known whether larger doses of vaccine, as are used for other groups with underlying disease, are more effective for HIV-infected children; some clinicians advocate using adult doses of vaccine to immunize HIV-infected children [76]. Periodic measurement of HBV antibody status is also recommended, especially if there is likely to be a risk of ongoing exposure [77]. HAV vaccine has a good safety profile, supporting its www.selleckchem.com/products/Everolimus(RAD001).html use in HIV-positive children, especially those with liver disease or HBV or hepatitis C virus (HCV) coinfection [78]. A study of the standard two-dose schedule given 1 month apart showed low antibody titres and limited persistence in 235 HIV-infected children on effective HAART; a third dose was found to be safe and resulted in increased antibody titres [79]. Another study demonstrated that all HIV-infected children, including those with HBV

coinfection, SAHA HDAC cost had adequate responses after two doses of HAV vaccine if given more than 6 months apart [80]. Combined HAV and HBV vaccines are advantageous for HIV-infected children as they minimize the number of injections received. As for HBV, the adult preparation may be preferable but this strategy is not yet evidenced. Annually revised seasonal influenza vaccines contain killed viruses and so are safe for HIV-infected

children over 6 months of age; two doses are given in the first year of receiving the vaccine, and then a single dose is given annually thereafter, ideally before the influenza season begins. Evidence on efficacy in HIV-positive children on HAART is limited. A study comparing influenza vaccine responses in healthy versus HIV-infected children showed poor antibody responses in the latter, despite effective HAART [81]. Thus, in addition (-)-p-Bromotetramisole Oxalate to vaccinating all HIV-positive individuals against seasonal flu annually, also vaccinating household contacts reduces exposure to influenza in the family setting. At the time of writing, seasonal influenza vaccines appear to confer little or no cross-reactive antibody responses to 2009 H1N1 [82], so vaccination against pandemic influenza strain A/H1N1 is currently recommended for all HIV-infected patients. A recent study using an MF59-adjuvanted H1N1 influenza vaccine demonstrated that it was immunogenic, safe and well tolerated in HIV-infected children and adolescents [83].

Many thanks to Professor Miles Fisher (Consultant Physician, Glas

Many thanks to Professor Miles Fisher (Consultant Physician, Glasgow Royal Infirmary) and Dr Gerry McKay (Consultant Physician, Glasgow Royal

Infirmary) for their support while writing this report. There are no conflicts of interest. “
“A 44-year-old gentleman with type 1 diabetes mellitus was found collapsed with diabetic ketoacidosis. Following correction of the metabolic derangements his level of consciousness improved but he became encephalopathic, exhibiting unprecedented aggression with non-specific neurological signs. This profound neurological find more state persisted for one month. Reversible causes of encephalopathy were investigated and excluded. The patient made a slow and almost complete recovery over a period of six months. Encephalopathy is an unusual complication of hyperglycaemic emergencies with poorly understood underlying mechanisms. This case demonstrates the importance of considering and treating the numerous reversible causes of an encephalopathic state before attributing altered levels of consciousness to the acute metabolic disturbances only. Copyright © 2010 John Wiley & Sons. “
“This

chapter contains sections titled: Embryology, anatomy and physiology of the thyroid gland Foetal and neonatal thyroid metabolism Thyroid function tests (TFTs) Definition and classification of thyroid disorders Rapamycin mw Neonatal hypothyroxinaemia, hyperthyrotropinaemia and transient neonatal hypothyroidism Congenital hypothyroidism Acquired hypothyroidism Hyperthyroidism Thyroid neoplasia Miscellaneous disorders Transition When to involve a specialist centre Future developments Controversial points Common pitfalls Significant guidelines/consensus statements Useful information

for patients and parents Case histories Further reading “
“Hypoglycaemia SPTLC1 is a common cause of presentation to emergency departments. Intentional overdose with long-acting insulin analogues is a recognised cause of hypoglycaemia; however, rates among those with insulin dependent diabetes are not well documented. Cases of intentional insulin overdose may be misdiagnosed as accidental, and therefore under-reported. This may be in part due to the narrow therapeutic index of the drug, as well as reluctance among patients to admit their intent.1 One retrospective study found that 90% of cases of insulin overdose were suicidal or parasuicidal.2 It has previously been reported that altered time effect profile occurs with massive overdose of long-acting insulin (i.e. duration of action greater than the expected 16–35 hours).3–5 The case described here is of interest because of the scale of the overdose, and the prolonged requirement for dextrose infusion. A 42-year-old man has had known type 1 diabetes since May 1997, usually maintained on a basal bolus regimen of approximately 8–18 units of NovoRapid and 30 units of glargine at night, with normal renal function.

In M-Nha, most Asp residues (14/19) were predicted to be in the h

In M-Nha, most Asp residues (14/19) were predicted to be in the hydrophobic region, while the alignment of M-Nha with Na+/H+ antiporters of another six microorganisms indicated that three aspartates, including Asp-138, Asp-167 and Asp-224, were conserved in M-Nha (Fig. 3). The protein encoded by m-nha gene showed a high similarity of 92%, 86% and 62% to NhaH from H. dabanensis D-8T, H. aidingensis AD-6T and B.

subtilis, respectively. Interestingly, M-Nha has a long carboxyl terminal hydrophilic tail (140 amino acid residues), similar to Nhap and NhaG type Na+/H+ antiporters, whereas NhaH does not. It was reported that both the ion specificity and activity of an Na+/H+ antiporter were partially determined by the structural properties of the C-terminal hydrophilic tail (Hamada et al., 2001; Waditee et al., 2001). NhaG from B. subtilis possesses a hydrophilic segment with >100 amino acid check details residues at the carboxyl terminal region (Gouda et al., 2001), and such a long hydrophilic domain is not present in any other microbial Na+/H+ antiporter except SynNhaP (NhaS1) in Synechocystis sp. (Hamada et al., 2001) and ApnhaP in A. halophytica (Waditee et al., 2001). The activities of NhaG decreased

when 26 residues in the C-terminal of the protein were lost (Gouda et al., 2001), and 56 residues in the C-terminal region of SynNhaP were necessary for antiporter activity (Hamada et al., 2001). Hydropathy analysis find more usually showed that the Na+/H+ antiporter had 10–12 hydrophobic and also probably membrane-spanning regions (Majernik et al., 2001; Yang et al., 2006). Our results also revealed that m-nha gene product fits well into this model. The NhaH Tacrolimus (FK506) and NhaG had 12 TMS, but M-Nha had only 10 TMS, although they all had high similarity of amino acid sequence. Consequently, the mechanism of ion transport by M-Nha from the Dagong Ancient Brine Well should be different from that of NhaH, NhaG and SynNhaP. With the differences of amino acid sequence and the putative secondary structure of the protein encoded

by m-nha from those Na+/H+ antiporter genes reported previously, it can be proposed that m-nha is a novel Na+/H+ antiporter gene. This study was significant in not only helping us understand the necessity of the existence of Na+/H+ antiporter in the Dagong Ancient Brine Well to maintain the intracellular environment homeostasis for halophiles, but also enriches our knowledge about the different mechanisms of Na+/H+ antiporter in halophiles in such an extreme environment. We thank Dr Terry A. Krulwich (Department of Biochemistry, Mount Sinai School of Medicine of the City University, New York) and Prof. Susheng Yang (Department of Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China) for donating the strain E. coli KNabc.