The level of mRNA for defensins was measured in total RNA prepara

The level of mRNA for defensins was measured in total RNA preparation by quantitative real time PCR as described in Methods. Expression of all genes was normalised to the expression of the endogenous reference gene GAPDH. The expression value in control cells was used as the baseline. Means followed by the same letter are not significantly different. Detection of the hBD2 peptide in human airway epithelial cells by immunofluorescence To determine if defensin peptides were present in the airway epithelial cells Selleckchem Belnacasan exposed to A. fumigatus, the hBD2 peptide was detected by immunofluorescence. Analysis of the hBD9 peptide was not performed since anti-hBD9 antibodies were not available. A549 or 16HBE cells were

cultured on cover slips, subsequently exposed to either SC, RC, HF, latex beads or treated with Il-1β for 18 h, and stained with polyclonal anti-hBD2 antibody as described in Methods. As shown in Figure 7A, hBD2 was detected in the cytoplasm of airway epithelial 16HBE cells exposed learn more to any of the morphotypes of A. fumigatus, but generally not in the untreated control culture or in the cells exposed to the latex beads, except for several individual cells that contained some amount of defensin peptides. These findings are consistent with the inducible expression of hBD2. Staining revealed the punctuated distribution of peptides

in the cytoplasm with a concentration in the perinuclear region. It should be observed that the expression of the hBD2 peptide was not detected in each cell of the sample exposed to A. fumigatus. Quantification of the differences in the number of cells detected with anti-defensin-2 antibody showed that the number of stained cells in the untreated control culture was 8 ± 4%. The percentage of stained cells increased to 32 ± 4.6% after Il-1 β-treatment, to 17 ± 4.5% after exposure to RC, to 28 ± 5.2% after exposure to SC and to 20 ± 5.1% after exposure to HF, while exposure to the latex Tyrosine-protein kinase BLK beads did not affect

defensin expression (9 ± 3.9%) (Figure 7B). Similar results were obtained with A549 cells (data not shown). Figure 7 Localisation of the hBD2 peptide in epithelial bronchial 16HBE cells. 16HBE cells were seeded at 5 × 105 cells per well in 1 ml of DMEM/F12 on 18-mm-diameter cover slips in 12 well plates in triplicate and grown for 16 h at 37°C. After washing the cover slips with PBS-BSA, the cells were exposed to either latex beads, ethanol fixed conidia or ethanol fixed HF for 18 hours. Il-1β was used as a positive control. Following washing with PBS, the cells were fixed with a paraformaldehyde solution for 30 min at 37°C. The slides were then incubated in 1% BSA/PBS-Triton 0.05%, followed by a solution of 10% normal goat serum. After washing, polyclonal rabbit anti-human hBD2 at a dilution of 1:250 was applied as primary antibody overnight at 4°C, followed by incubation with FITC-labelled goat anti-rabbit secondary antibody at a dilution of 1:300 for 4 hours at room temperature.

Table 1 DNA:DNA relatedness percentages between representatives o

Table 1 DNA:DNA relatedness percentages between representatives of two novel Enterobacter species and closely-related species   1 2 3 4 5 6 7 8 1 100               2 89(4) 100             3 33(16) 38(10) 100           4 31(17) 33(10) 93(6) 100         5 35(2) 33(9) 35(17) 31(7) 100       6 32(10) 35(2) 59(7) 58(3)

33(2) 100     7 39(9) 41(3) / 61(9) 43(8) 79(6) 100   8 33(8) 31(1) 63(8) 60(14) 33(21) 66(17) 71(2) 100 The data are based on means of at least 4 hybridizations. The values given between brackets are the differences between the reciprocal values. Taxa: 1, Enterobacter oryzendophyticus REICA_032; 2, Enterobacter oryzendophyticus REICA_082T; 3, Enterobacter oryziphilus REICA_142T; 4, Enterobacter oryziphilus REICA_191; 5, Enterobacter cowanii LMG 23569T; 6, Enterobacter radicincitans LMG 23767T; 7, Enterobacter oryzae LMG 24251T; 8, Enterobacter

arachidis LMG 26131T. CH5183284 Furthermore, group-I type strain REICA_142T DNA showed only about 35-60% relatedness with the DNA of the closest relatives E. arachidis LMG 26131T (63% ±8), E radicincitans LMG 23767T (59% ±7) and E. cowanii LMG selleckchem 23569T (35% ±17). This finding is consistent with the contention that the group-I strains indeed form a separate species, within the genus Enterobacter. Similarly, strain REICA_082T genomic DNA revealed relatedness values that were significantly below the 70% cut-off value with that of the closest-related strains E. oryzae LMG 24251T (41% ±3), E. radicincitans LMG 23767T (35% ±2), E. cowanii LMG 23569T (33% ±9) and E. arachidis LMG 26131T (31% ±1) (Table 1). Again, this finding supports our contention that also the group-II strains form a separate species within the genus Enterobacter. It was interesting to note that the DNA-DNA relatedness values between E. radicincitans LMG 23767T and E. oryzae LMG 24251T (79% ±6) and between E. radicincitans LMG 23767T and E. arachidis LMG 26131T (66% ±17), in our experiments, were much higher than those reported by the original authors [3]. Support for the robustness

of our data is provided by the phylogenetic relationships revealed by the rpoB gene sequences, where E. radicincitans D5/23T and E. arachidis Phosphoribosylglycinamide formyltransferase Ah-143T were 98.9% similar. These data were further consistent with the cellular fatty acid profile data (see below), which were indistinguishable at strain level. The overall genomic DNA G+C content was determined according to the HPLC method [20] using the DNA prepared for the DNA:DNA hybridization analyses. The values (means of three independent analyses of the same DNA sample) for the selected group-II strains REICA_032 and REICA_082T and group-I strains REICA_142T and REICA_191 were 52.7, 52.9, and 52.1 and 51.7 mol%, respectively. These values are within the lower range of the DNA mol% G + C, i.e. 52–60 %, of all members of the genus Enterobacter[21].

5% of body mass loss) exercise can be prolonged to a greater exte

5% of body mass loss) exercise can be prolonged to a greater extent than with water ingestion only [7]. Although speculative, AG ingestion may have augmented fluid uptake from the gut, and minimized the potential deleterious effects that mild levels of dehydration had on nerve conduction and brain function. These effects

may be more prevalent in activities involving multisensory information such as shooting (involves a coordinated and precise visual and motor control of the hands and arms) versus reaction of the lower body. In conclusion, rehydration with AG appears to maintain basketball skill performance and visual reaction time to a greater extent than water only. These effects are likely mediated by enhanced fluid and electrolyte check details uptake from the gut and subsequent preservation of neural function that commands physical activities involving fine motor control. Further research appears warranted in the examination of AG ingestion and neural activity during periods of hydration stress. Acknowledgements The authors would like to thank a dedicated group of subjects. This study Dinaciclib was supported by a grant from Kyowa Hakko USA, New York, NY. References 1. Nath SK, Dechelotte P, Darmaun D, Gotteland M, Rongier M, Desjeux JF: ( 15 N) and ( 14 C) glutamine fluxes across rabbit ileum

in experimental diarrhea. Am J Physiol 1992, 262:G312-G318.PubMed 2. Silva AC, Santos-Neto MS, Soares AM, Fonteles MC, Guerrant RL, Lima AA: Efficacy of a glutamine-based oral rehydration solution on the Metalloexopeptidase electrolyte and water absorption in a rabbit model of secretory diarrhea induced by cholera toxin. J Pediatr Gastroenterol Nutr 1998, 26:513–519.PubMedCrossRef

3. van Loon FP, Banik AK, Nath SK, Patra FC, Wahed MA, Darmaun D, Desjeux JF, Mahalanabis D: The effect of L-glutamine on salt and water absorption: a jejuna perfusion study in cholera in humans. Eur J Gastroenterol Hepatol 1996, 8:443–448.PubMed 4. Li Y, Xu B, Liu F, Tan L, Li J: The effect of glutamine-supplemented total parenteral nutrition on nutrition and intestinal absorptive function in a rat model. Pediatr Surg Int 2006, 22:508–513.PubMedCrossRef 5. Lima AA, Carvalho GH, Figueiredo AA, Gifoni AR, Soares AM, Silva EA, Guerrant RL: Effects of an alanyl-glutamine-based oral rehydration and nutrition therapy solution on electrolyte and water absorbtion in a rat model of secretory diarrhea induced by cholera toxin. Nutr 2002, 18:458–462.CrossRef 6. Fürst P: New Stem Cells inhibitor developments in glutamine delivery. J Nutr 2001,131(suppl):2562–2568. 7. Hoffman JR, Ratamess NA, Kang J, Rashti SL, Kelly N, Gonzalez AM, Stec M, Andersen S, Bailey BL, Yamamoto LM, Hom LL, Kupchak BR, Faigenbaum AD, Maresh CM: Examination of the efficacy of acute L-Alanyl-L-Glutamine during Hydration Stress in Endurance Exercise. J Int Soc Sports Nutr 2010, 7:8.PubMedCrossRef 8.

Materials and methods These observations were performed on patien

Materials and methods These observations were performed on Buparlisib cell line patients presenting to the 228th Combat Support Hospital (CSH), Company B, at Forward Operating Base Speicher, outside CB-5083 mw of Tikrit, Iraq, between the dates of June 15 and September 11, 2005. These observations were performed during use of the

Inspectra™ 325 as a clinical monitor (Figure 2). The Brooke Army Medical Center Institutional Review Board waived the need for informed consent. The Inspectra™ StO2 tissue oxygenation monitor (Hutchinson Technology, Inc; Hutchinson, MN, USA) is currently FDA-approved for use in monitoring patients continuously during circulatory or perfusion examinations of skeletal muscle, or when there is a suspicion of compromised circulation. A recent large observational and descriptive study found a mean thenar StO2 of 87 ± 6% in 707 normal human volunteers [9]. In the

present observations, a 70% cutoff value of StO2 was selected to screen for patients to be followed in time BAY 1895344 molecular weight because data obtained from severely injured trauma patients has verified that a StO2 value of less than 75% is predictive of multiple organ failure and mortality [10]. Figure 2 The non-invasive StO 2 probe is placed directly over the thenar eminence of the patient. The device will continuously generate StO2 readings every 4 seconds. Patients were brought to the 228th CSH via ground ambulance or helicopter after traumatic injury. Patients were evaluated by a team of physicians and health care providers using a standardized ATLS protocol and after stabilization taken as appropriate to the operating room and/or prepared for transfer to a higher

level of care. Patients were monitored during resuscitation and early evaluation using clinical parameters, continuous EKG and pulse oximetry, and other monitors (e.g. bladder catheterization) as appropriate. In situations where more than one patient was evaluated concurrently, an attempt was made to place the StO2 monitor on the most severely injured patient. Convenience samples of demographic data, vital signs, laboratory data, and StO2 data were collected Paclitaxel datasheet on patients as patient care permitted. Case presentations Between June 15 and September 11, 2005, there were 161 patients evaluated at the 228th CSH, Co B as a result of traumatic injury. The StO2 monitor was placed on approximately 40 patients during this period of time. In most patients, StO2 readings of greater than 70% were noted during the initial evaluation. No further information was collected from these patients. In 8 patients, convenience samples of StO2 data were collected along with pertinent physiologic data. In these patients, StO2 levels of below 70% tracked with hypotension, tachycardia, and clinical shock resulted in increases in StO2 after resuscitation maneuvers (Table 1).

For instance, they are resistant to antimicrobial agents in compa

For instance, they are resistant to antimicrobial agents in comparison to planktonic cells [6–8]. As more than 65% of biofilms with human microbial infections are caused by biofilms [5], there is an urgent need to

understand biofilm behaviour. The genus 7-Cl-O-Nec1 datasheet Candida comprises more than 150 pathogenic and nonpathogenic yeast species. Among these, C. albicans, C. tropicalis, C. parapsilosis, C. krusei, C. kefyr, C. glabrata and C. guillermondii are recognized as medically important pathogens [9]. C. albicans is the most prevalent yeast isolated from humans (47-75%) followed by C. tropicalis (7%), C. glabrata (7%), C. krusei (5%), C. parapsilosis (< 5%) and C. guillermondii (< 5%) [9]. Common Candidal habitats of humans include the gut, skin and mucosal surfaces, while one half of the human population

carry Candida in their oral cavities[10]. Pseudomonas aeruginosa is an DZNeP concentration AZD5582 cell line aerobic Gram-negative bacterium that causes community acquired infections, such as ulcerative keratitis, otitis externa, skin and soft tissue infections and, nosocomial infections including pneumonias, urinary tract infections, infections in surgical sites and burns [24, 25]. Indeed, out of all nosocomial infections in different ethnic communities, 11-13.8% is found to be caused by P. aeruginosa [11–13]. United States Cystic Fibrosis Foundation Patients Registry (2004), has stated that 57.3% of all reported respiratory cultures contained P. aeruginosa indicating its important role in causing chronic and recurrent infections in cystic fibrotic patients [14]. Lee et al [15] have demonstrated that P. aeruginosa is the most commonly identified cause of septicemia in primary immunodeficiency and some 20% of bacteriaemia in acute leukemic patients [16, 17]. Incidence of P. aeruginosa bacteriaemias in HIV affected patients is approximately MRIP 10 times higher

than that of the normal population [18]. Pathogenic interactions between C. albicans and P. aeruginosa have recently been demonstrated by a number of groups [19, 20]. The antifungal behaviour of P. aeruginosa against Candida spp. was first reported in early nineties by Kerr et al [20]. Subsequently others have shown that P. aeruginosa kills C. albicans by forming a dense film on fungal filaments, though, it neither binds nor kills the yeast-form of C. albicans [19]. Thein et al [21] have also reported that P. aeruginosa ATCC 27853 at a concentration gradient elicited a significant inhibition of Candida albicans biofilms. Although, the structure and the properties of monospecies biofilms and their role in disease have been extensively studied during the last decade [22, 23], the interactions within mixed biofilms consisting of bacteria and fungi including Candida spp. have not been studied in depth. Furthermore, the majority of the previous studies on interactions between Candida and bacteria in mixed biofilms have focused on C. albicans and there are only a few studies on non-albicans Candida spp.


Intron splicing is a precisely regulated process, where only four intron sequences guide spliceosome machinery. They are: the exon-intron junction at the 5′ and 3′ end of the introns (5′ss – GT, 3′ss – AG); the branch site sequence located upstream of the 3′ss; and the polypyrimidine tract located between

the 3′ss and the branch site [6]. The aquatic fungus Blastocladiella emersonii belongs to the Chytridiomycete class, which is at the base of the fungal phylogenetic tree [7, 8]. Throughout its life cycle this fungus suffers dramatic biochemical and morphological changes, especially during two distinct stages of cell differentiation: germination and sporulation [9]. Both stages can be induced with a high degree of synchrony, and drastic changes in the patterns of RNA and Citarinostat in vivo protein syntheses are observed throughout the fungus life cycle. In nature, B. emersonii can Fosbretabulin be exposed to distinct environmental conditions, as temperature fluctuations and presence of heavy metals, as cadmium, that could lead to the disruption of some cellular functions. It was previously shown that the splicing machinery is sensitive to thermal stress, as exposure of Saccharomyces cerevisiae cells to heat shock at 42°C leads to the accumulation

of pre-mRNA species containing unspliced introns [10]. This splicing inhibition was also observed in a variety of species from yeast to humans, including B. emersonii [10–14]. However, the splicing machinery seems to be more thermoresistant in B. emersonii because at the lethal temperature of 42°C, when cell viability falls to less than 1% and protein synthesis is decreased by more than 95% [15], splicing selleck inhibitor is only partially inhibited in this fungus (30% inhibition) [13]. In yeast and Drosophila melanogaster at extreme temperatures splicing is inhibited more than 70% [10, 11]. Although the effects of heat shock in the splicing machinery have been known for more

than two decades [11], there is little information in the literature about how cadmium affects this complex. Cadmium (Cd2+) is a divalent cation present in polluted environments, which causes oxidative stress, lipid peroxidation and mutagenesis in the cells [16, 17]. However, the molecular mechanisms by which cadmium leads to ABT-263 clinical trial reactive oxygen species production and oxidative stress are largely unknown and are probably indirect. The mechanism usually proposed for cadmium toxicity is its binding to cellular proteins, resulting in the inhibition of some essential enzymes. As cadmium has high affinity for thiol groups, it is thought to bind accessible cysteine residues in proteins [16]. Another possible effect of cadmium exposure is the displacement of zinc and calcium from metalloproteins, leading to inhibition of these important proteins [16–18]. In this way, the presence of cadmium in the cells could affect, in theory, any biological process including the spliceosome machinery.

That is, all subjects adapted to a similar degree, yet those in t

That is, all subjects adapted to a similar degree, yet those in the DI group demonstrated significant reductions in volume load versus the CI group (see Tables 1 and 2). According to the Position Statement of International Society of Sports Nutrition, CR monohydrate (and not other forms of CR) is the most effective ergogenic nutritional supplement currently available to athletes in terms of increasing high-intensity exercise capacity and lean body mass during training [4]. To date, several hundred peer-reviewed research studies have been conducted to evaluate the efficacy

this website of CR supplementation in improving exercise performance. Nearly 70% of these studies have reported a significant improvement in exercise capacity, while the others have generally reported non-significant gains in performance [34]. Arciero et al. [35] compared 1-RM strength gains after 4 weeks of CR supplementation with or without resistance training. Bench press and leg press 1-RM were increased 8 and 16%, respectively, in the CR alone group and 18 and 42%, respectively, in the training group. This study suggests that approximately 40% of the increase in strength over the 4-week training and CR supplementation period is due to the acute effects of CR on force production, with selleck compound the remaining

60% due to some other mechanism, presumably an ability to train with higher workloads. Syrotuik et al. [36] reported that when training volume is equal, subjects ingesting CR or placebo experienced similar increases in muscle strength and weightlifting performance following an 8-week resistance training program. Thus, it is probable that subjects who ingest CR during resistance training do more work than those who do not [32, 33].

Again, this assumes that rest interval length remains constant, unlike the present design. Larson-Meyer et al. [27] conducted a double-blind, placebo-controlled study, which involved 14 division I female soccer players during their 13-week off-season resistance training program. Seven of the women were GBA3 CR loaded with approximately 7.5 g twice daily for 5 days, and then maintained their CR intake at 5 g/day for the remainder of the study. Following a repeated selleckchem measures analyses to establish trial by group interactions, it was determined that bench-press and squat 1-RM strength improved more for the CR group compared with the placebo group. There was, however, no difference between the two groups concerning overall gains in lean tissue as determined by dual energy x-ray absorptiometry (DXA). To our knowledge, the current study was the first to compare the chronic effects of CR supplementation in a training program using decreasing rest intervals between sets and exercises to a program using constant rest intervals. In strength-type regimens, the recommended rest interval of 2-5 minutes between sets has been shown to allow for consistent repetitions, without large reductions in the load [37–40].

The plasmon band shifts to higher values with the increase of tom

The plasmon band shifts to higher values with the increase of tomato concentration in the aqueous extract. At concentrations higher than this, the plasmon band shifts to 540 nm, and the extinction selleck products coefficient of the band decreases appreciably. Here, the tomato extract of 5:5 composition has been used throughout. Figure 2 UV–VIS absorption spectra of GNP at different compositions of tomato extract and SDS capped GNP in check details alkaline medium. UV-VIS spectra of (A) GNP at different compositions and (B) SDS-capped GNP. Insets

are digital photographic images of A and B. Shifting of gold plasmon band to the higher value may be explained as follows: tomato extract is a strong reducing agent but not a good capping agent. So, it induces rapid nucleation but cannot restrict FRAX597 cost the growth of gold nanoparticles. Hence, polydispersed gold nanoparticles are observed. When we use tomato extract (100%), the band shifts to 540 nm and the extinction coefficient decreases appreciably.

This might be due to colloidal instability. The polydispersity and the colloidal instability (agglomeration tendency of gold nanoparticle) may be the reason for a broad spectrum of gold sol along with a shift in the peak position. The shifting of the peak position may be related to the increase of the size of gold nanoparticles. To examine the sensor properties of the GNP, the solution was made Tyrosine-protein kinase BLK alkaline by adding different amounts of NaOH (0.15 (M)). For these studies, the pH of the solution was maintained near 9 to 9.5 by adjusting the amount of NaOH in the solution, and a surfactant SDS was added to stabilize the medium. Here, SDS acts as a capping agent, due to which the SPR band shifts to 532 nm (Figure 2B). A comparatively sharp spectrum with absorbance at 532 nm was observed in this case. This can be explained from the fact that SDS, being a strong capping agent, stabilizes the gold nanoparticles as soon as nucleation happens and so restricts the maximum size of the nanoparticles. As a result, we obtained nearly

monodispersed GNP. Methyl parathion was added to these alkaline solutions containing SDS in varying concentrations ranging from 10 to 200 ppm, and the change of absorption coefficient was observed. As soon as methyl parathion was added, we observed a new peak at around 400 nm in addition to the peak found at 532 nm. More interestingly, absorbance at 400 nm, the newly found peak, is seen to increase when the concentration of methyl parathion increased from 10 to 200 ppm (Figure 3A). Figure 3 UV–vis spectra of GNP and with methyl parathion, calibration curve (absorbance versus methyl parathion), and control spectrum. (A) UV–vis spectra of GNP and GNP with various concentrations of methyl parathion 10 to 200 ppm; (inset) digital photographic images of color changes due to addition of methyl parathion.

Figure 1 Hierarchical clustering analysis of 913 genes from Affym

Figure 1 Hierarchical clustering analysis of 913 genes from Affymetrix array analysis showing differential expression patterns during SL1344 (WT AvrA) infection and SB1117(AvrA-) infection. Semaxanib supplier A indicates repressed gene cluster at 8 hours and 4 days; B indicates a up-expressed gene cluster at 8 hours but a down-expressed cluster at 4 days; C indicates a down-expressed gene cluster at 8 hours but a up-expressed cluster at 4 days; and D indicates an induced gene cluster at 8 hour and 4 days. Subset group was indicated with*. The heat map was built by using Gene Cluster 3.0 software. Red color represents up-regulation and green shows

down-regulation. We further identified some subset groups (indicated with *), which suggested that SL1344 and SB1117 infection differentially regulated genes at both the early stage and the late stage. These results indicate that AvrA is involved in altering host responses

in the Salmonella-intestine interaction in vivo. Characteristics of differentially expressed genes between the SL1344 and SB1117 infection groups Our cluster analysis CB-839 mw for the SL1344 (AvrA+) and SB1117 (AvrA-) infection groups have indicated that AvrA expression in the Screening Library manufacturer salmonella strains clearly alters the in vivo host responses to intestinal infection. In order to get a broad overview of the mouse colon transcriptional changes induced by Salmonella Typhimurium SL1344 effector AvrA, fold change in gene expression was calculated

for each SL1344 infection group relative to each SB1117 infection group (Figure 2). Figure 2 The number of differentially expressed genes between infection with salmonella, SL1344 (WT, AvrA) and SB1117(AvrA-). In the SL1344 infection group, compared to the SB1117 infection group, at 8 hours post infection, Edoxaban 347 (58%) genes were up-regulated and 227 genes (42%) were down-regulated (Figure 2 and Additional file 2 Table S2, Fold times ≥1.2 times, P ≤ 0.05). In the SL1344 infection group at 4 days, 268 genes (44%) in the group were up-regulated and 337 genes (56%) were down-regulated, compared to the SB1117 infection group (Figure 2 and Additional file 3 Table S3, Fold times ≥1.2 times, P ≤ 0.05). The majority of the genes that were differentially expressed between groups showed moderate alterations in expression of 1.2 to 2.0 folds (Additional file 2 Table S2 and Additional file 3 Table S3). Overall, the results indicate that AvrA protein by TTSS must be responsible for the induction and repression of in vivo transcriptional reprogramming of the host cells in intestinal infection (Figure 2).

681 0 055 Weston (Caucasian) 6 27 32 3 42 72 1 189 0 276 Weston (

681 0.055 buy GSK2879552 Weston (Caucasian) 6 27 32 3 42 72 1.189 0.276 Weston (African) 6 9 1 12 14 4 0.001 0.979 Li 11 11 6 10

26 14 0.109 0.741 Wang-Gohrke 282 221 49 300 203 40 0.485 0.486 Buyru 64 39 12 21 43 12 1.657 0.198 Huang 64 100 36 114 138 30 1.545 0.214 Katiyar 20 51 6 9 24 8 1.205 0.272 Mabrouk 18 9 3 19 26 4 1.432 0.231 Kalemi 26 13 3 10 32 9 3.326 0.068 Tommiska 825 617 109 403 278 52 0.183 0.669 Baynes 1107 768 148 1177 854 166 0.414 0.520 Gochhait 86 109 48 76 160 97 0.413 0.521 Khadang 83 109 29 75 90 40 1.873 0.171 Schmidt 2797 2008 386 2024 1523 287 0.001 Compound Library cell assay 0.983 Sprague 823 570 89 705 490 83 0.03 0.862 Zhang 21 45 17 47 find more 87 33 0.406 0.524 Akkiprik 25 50 20 46 49 12 0.038 0.846 Test of heterogeneity We analyzed the heterogeneity of Arg/Arg versus Pro/Pro and dominant

model (Arg/Arg+Arg/Pro versus Pro/Pro) as well as recessive model (Arg/Arg versus Arg/Pro+Pro/Pro). of cases/controls Arg/Arg vs Pro/Pro (Arg/Arg+Arg/Pro) vs Pro/Pro Arg/Arg Oxalosuccinic acid vs (Arg/Pro+Pro/Pro)     OR (95%CI) P P (Q-test) OR (95%CI) P P (Q-test) OR (95%CI) P P (Q-test) Random-effect model Total 12226/10782 1.20 (0.96–1.50) 0.11 0.000 1.12 (0.96–1.32) 0.14 0.01 1.13 (0.98–1.31) 0.10 0.000 Caucasian 11549/9830 1.15 (0.91–1.44) 0.24 0.001 1.11 (0.95–1.30) 0.17 0.06 1.09 (0.93–1.27) 0.28 0.000 Asian 631/873

1.36 (0.61–3.03) 0.45 0.000 1.19 (0.67–2.10) 0.55 0.006 1.22 (0.72–2.05) 0.46 0.002 African 46/79 1.46 (0.38–5.62) 0.58 0.76 1.12 (0.31–4.10) 0.86 0.45 1.60 (0.63–4.06) 0.32 0.22 Fixed-effect model Total 12226/10782 1.09 (0.99–1.20) 0.10 0.000 1.09 (0.99–1.19) 0.06 0.01 1.04 (0.99–1.10) 0.13 0.000 Caucasian 11549/9830 1.07 (0.96–1.18) 0.24 0.001 1.08 (0.98–1.19) 0.12 0.06 1.03 (0.98–1.09) 0.25 0.000 Asian 631/873 1.27 (0.94–1.71) 0.12 0.000 1.16 (0.89–1.51) 0.26 0.006 1.15 (0.92–1.44) 0.22 0.002 African 46/79 1.47 (0.39–5.62) 0.57 0.76 1.17 (0.33–4.14) 0.80 0.45 1.67 (0.80–3.48) 0.17 0.22 Meta-analysis results Table 3 lists the main results of the meta-analysis.