The

genetic basis for the aberrant immune response in susceptible individuals is not clearly defined. Several years ago we discovered that inbred strains of mice vary over 4 logs in their susceptibility to infection with C. immitis and that resistance is the dominant phenotype [10]. This proved to be a polygenic trait, and a resistance locus was identified on chromosome 6 using recombinant inbred BXD lines [11]. C57BL/6 mice are more sensitive to infection with C. immitis than DBA/2 mice such that nearly all C57BL/6 mice die between day 16 and 18 post-infection [10]. We have shown that infected C57BL/6 mice make more IL-10 and IL-4 and less interferon gamma (IFN-γ) in their lungs compared to DBA/2 mice [12]. IL-10 has pleiotropic effects on Selleckchem Tamoxifen different cell types that affect the acquired immune response

resulting in inhibition of the development of Th1 immune responses [13]. In the current work, microarray analysis was used to identify genes differentially expressed between lung tissue samples from resistant DBA/2 and sensitive C57BL/6 mice following infection with C. immitis. Differentially expressed genes were mapped onto biological pathways, gene ontologies and protein networks in order to fully characterize the biological processes HDAC inhibitors in clinical trials that contribute to a protective response against C. immitis infection. Results C. immitis infection in DBA/2 resistant versus sensitive C57BL/6 mice The colony forming units (CFUs) in the right (R) lung and spleen of DBA/2 and C57BL/6 mice were determined after intra-nasal (i.n.) infection with C. immitis arthroconidia. We chose three time points after infection ADP ribosylation factor for analysis

(day 10, 14 and 16). Since mice were only infected with 50 CFU and not all of them were inhaled, day 10 is the earliest day when there are enough organisms in the lungs to reliably quantitate pulmonary infection in all mice. C57BL/6 mice began to die on day 16 so this was selected as the last time point, and day 14 was chosen as an intermediate time point. On day 10 after infection there were equal numbers of CFU in the lungs of both strains of mice and we could not detect dissemination by culturing their spleens (Figure 1). On day 14 and 16 post-infection DBA/2 mice had 10 to 100 fold fewer CFU/lung, and in this experiment no DBA/2 mice had detectable dissemination to the spleen, whereas all the C57BL/6 mice had positive spleen cultures. Figure 1 Comparison of C. immitis infection between resistant DBA/2 and sensitive C57BL/6 mice. Mice were infected (i.n.) and then sacrificed at the indicated intervals. The right lung and spleen of each mouse was homogenized and cultured quantitatively. Each symbol represents an individual mouse and the horizontal lines are the geometric mean ± standard error of the mean.

Phys Rev B 1972, 6:4370–4379.CrossRef 40. Kabashin AV, Evans P, Pastkovsky S, Hendren W, Wurtz GA, Atkinson R, Pollard R, Podolshiy VA, Zayats AV: Plasmonc nanorod metamaterials for biosensing. Nat. Mater. 2009, 8:867–871.CrossRef 41. Wurtz G, Pollard R, Hendren W, Wiederrecht G, Gosztola D, Podolskiy V, Zayats A: Designed ultrafast optical nonlinearity in a plasmonic nanorod

metamaterial enhanced by nonlocality. Nat Nanotechnol 2011, 6:106–110.CrossRef 42. Pollard R, Murphy A, Hendren W, Evans P, Atkinson R, Wurtz G, Zayats A: Optical nonlocalities and additional waves in epsilon-near-zero metamaterials. Phys Rev Lett 2009, 102:127405.CrossRef 43. Nielsch K, Müller F, Li AP, Gösele U: Uniform nickel deposition into ordered Selleckchem MK1775 alumina pores by pulsed electrodeposition. Adv Mater 2000, 12:582–586.CrossRef 44. Novotny L, Hecht B: Principles of Nano-optics. Cambridge: Cambridge University Press; 2006.CrossRef 45. Wang QQ, Han JB, Guo DL, Xiao S, Han YB, Gong HM, Zou XW: Highly efficient avalanche multiphoton luminescence from coupled Au nanowires in the visible region. Nano Lett 2007, 7:723–728.CrossRef Competing interests The authors declare that they have no competing interests. Authors’ contributions

JX, ZKZ, ZL, and JY prepared the samples. JX, QZ, and ZKZ anticipated the optical experiments and analyzed the related experiment data. JX, ZKZ, and YL characterized the morphology of the samples. JX Saracatinib molecular weight and ZKZ performed the simulations using FDTD solution and interpreted the simulation results. JML, JTL, and XHW performed the numerical simulation of Liothyronine Sodium the LDOS section. ZKZ proposed the pulse AC growth method and finalized the manuscript. All authors read and approved the final manuscript.”
“Background The rapid proliferation of advanced electronic devices for many commercial and military applications, such as data transmission, telecommunications,

wireless network systems, and satellite broadcasting as well as radar and diagnostic and detection systems, has led to numerous electromagnetic compatibility and electromagnetic interference (EMI) problems. The interaction of electromagnetic waves originating from different sources can lead to a decrease in quality and a misinterpretation of transferred data, and it has thus become vital to avoid such interference and electromagnetic wave pollution through the use of appropriate absorbing and shielding materials. Carbonaceous materials – such as graphite and/or carbon black – are often used as dielectric electromagnetic absorbers, generating dielectric loss by improving the electrical conductivity of the mixture. In particular, nanostructured materials and carbon fiber composites have been the subjects of growing interest as microwave radiation absorbing and shielding materials in the high-frequency range due to their fascinating properties [1–5].

Enteritidis (wt) and ΔSPI2 mutant. n.i. – non-infected mice. * – t-test different from the non-infected mice at P < 0.05. Finally we tested whether the depletion of NK cells could be caused by their migration to the caecal lamina propria. We therefore infected mice with wild type S. Enteritidis and ΔSPI2 mutant, and besides the spleen we also determined the counts of the NK cells in blood and ZVADFMK the lamina propria. In blood, a significant decrease in NK cells post

wild-type S. Enteritidis infection was observed. In the lamina propria, the numerical increase in NK cells was observed although this increase did not reach statistical significance (Figure 8). Figure 8 Distribution of NK cells in spleen, blood and caecal lamina propria of mice infected with the wild type

S . Enteritidis (wt) and ΔSPI2 mutant as determined in the animal infection 4. n.i. – non-infected mice. * – t-test different from the non-infected mice at P < 0.01. Discussion Similar to the observations of others, progress of the infection in mice, characterised by fecal shedding, fatalities, liver and spleen colonisation and liver injury, was dependent on the presence of SPI-2 but not any other SPI [3, 17, 18]. The exclusivity of SPI-2 dependence for S. Enteritidis virulence for mice was such that even in the absence of all remaining SPIs, i.e. in the case of SPI2o mutant, this mutant was capable of causing typhoid similar to that caused by the wild-type

strain. This observation ICG-001 purchase was slightly unexpected for the mutants without SPI-1. However Murray and Lee already reported on minimal influence of the removal of the whole SPI-1 on the virulence of S. Typhimurium for Balb/C mice [18] and also single gene mutants in sopB, sopD or sipA were only weakly attenuated [19, 20] or the attenuation Casein kinase 1 was expressed only as a minor delay in mean time to death [21]. In addition, dose dependent difference in the virulence of sopB mutant of S. Typhimurium was described [20] and since we used only a single dose corresponding to 100× LD50, minor phenotypic differences associated with the presence or absence of SPI-1 could remain undetected. The infection did not influence the counts of T- and B-lymphocytes in the spleen at the time of sampling, similarly to the findings of Geddes et al [12]. We did not even observe an increase in γδ T-lymphocytes although these were reported to increase in mice after infection with a virulence plasmid-cured derivative of S. Choleraesuis [22]. Although there were no changes in these cell populations, general immunosuppression has been observed when PHA was used as the mitogen for stimulation. Since the immunosuppression was not observed when ConA and PHW were used for the stimulation, it can be expected that the population which was primarily immunosuppressed was that represented by the CD4 Th lymphocytes [23].

aureus is the transfer of the sn-1-glycerol-PO4 headgroup of PtdGro to the growing LTA polymer by LtaS [32]. The DAG formed from PtdGro utilization in this pathway has two metabolic fates: 1) DAG is converted to PtdOH by DkgB [33] and recycled back toward PtdGro via CDP-DAG, or 2) DAG is converted to GlcDAG and Glc2DAG by YpfP [34], which serves as the scaffold for glycerol-PO4 Bortezomib polymerization

in LTA synthesis. In the absence of a glycerol-PO4 supplement, the PtdGro in the ΔgpsA cells cannot be remade due to the requirement of PtdGro synthase for glycerol-PO4 resulting in the accumulation of PtdOH and CDP-DAG intermediates. Interestingly, the levels of neither Glc2DAG nor Lys-PtdGro, via MprF [35], increased in the glycerol-depleted cells suggesting that the synthesis of these two membrane lipids is linked to the synthesis of new PtdGro. A striking result was the upregulation of cardiolipin synthesis in the glycerol deprived cells. S. aureus possesses two cardiolipin synthase genes [36–38]. The accumulation of cardiolipin in stationary phase is attributed to Cls2, whereas cardiolipin synthesis in response to physiological stress depends on Cls1. The Cls1 stress response was rapid and does not require new protein synthesis [38]. Which of these Cls enzymes is responsible for the activation of cardiolipin synthesis in the absence of glycerol-PO4 remains to be determined. However, the conversion

of PtdGro to cardiolipin appears to be a logical stress response Opaganib cell line to glycerol deficiency because the net effect is the release of intracellular glycerol that could be used to support PtdGro biosynthesis. The

data also suggest that the coupling of fatty acid synthesis and phospholipid has features that are similar to those Dichloromethane dehalogenase observed in E. coli. The removal of the glycerol supplement results in diminished fatty acid synthesis that correlates with the accumulation of acyl-ACP. These accumulated acyl-ACPs are long-chain acyl-ACP end-products, and there is no evidence for the accumulation of acyl-ACP pathway intermediates. The fact that acyl-ACP does not rise to consume the entire ACP pool points to the regulation occurring at the initiation of fatty acid synthesis at the FabH step. This conclusion is consistent with the increased levels of malonyl-CoA, which indicate that the supply of malonyl groups is sufficient to complete the synthesis of an initiated acyl chain. However, malonyl-CoA levels only rose to 3.7% of the acetyl-CoA pool in the glycerol-deprived cells pointing to a biochemical regulatory mechanism that constrains the activity of acetyl-CoA carboxylase. FabH and acetyl-CoA carboxylase are key regulatory points in E. coli where acyl-ACP is thought to be the biochemical regulator of these two enzymes [11, 12]. Our in vivo data are consistent with acyl-ACP targeting the same two proteins in S. aureus as in E.

As shown earlier, [19] and corroborated

here (Fig. 7), the tertiary structure of all inserted domains is very similar, although the degree of amino acid identity is rather low. In general, we have hypothesized three different mechanisms of how Usp domain swapping could affect KdpD/KdpE signaling: (i) UspC scaffolding under salt stress is increased/abolished due to affinity alterations of the inserted domains towards UspC, (ii) the enzymatic activities of the KdpD chimeras are altered, and (iii) the protein dynamics of the sensor are altered. Interestingly, we generated chimeras covering all these possibilities. Scaffolding under salt stress was only observed when UspC was inserted into KdpD. In contrast, all other domains prevented scaffolding by UspC. It should be noted that the KdpD-Usp domain sequences differ among bacteria, and also Dabrafenib the set of available soluble Usp proteins within these bacteria is variable. A. tumefaciens has three usp homologues (atu0496,

atu0904, and atu1730), S. coelicolor has eleven usp homologues (sco0172, sco0178, Ku-0059436 in vitro sco0167, sco0180, sco0181, sco0198, sco0200, sco0937, sco7156, sco7247, and sco7299), P. aeruginosa has seven (pa1753, pa1789, pa3017, pa3309, pa4328, pa4352, and pa5027), and S. enterica serotype Typhimurium has six homologues similar to E. coli (uspA, uspC, uspD, uspE, uspF, and uspG). With the exception of S. enterica, none of these organisms has a uspC homologue, suggesting that KdpD/KdpE scaffolding either does not exist in these bacteria, or it is mediated by

other Usp proteins. This leads to the conclusion that UspC is the specific scaffolding protein for KdpD/KdpE in E. coli. Although all chimeras exhibited enzymatic activity, the ratio between kinase-phosphotransferase to phosphatase activity was shifted in some chimeras. In Pseudocoli-KdpD, the ratio was shifted towards the phosphatase activity, producing a significantly lower expression level than wild-type KdpD. Likewise, KdpD-UspC and Streptocoli-Usp had increased kinase-phosphotransferase to phosphatase ratios and were characterized by significantly higher induction values compared to wild-type KdpD. Last but not least, the “”domain swapping”" approach identified the first two KdpD derivatives (KdpD-UspG and KdpD-UspF) with alterations in Smoothened the N-terminal domain that lost the sensing/signal processing (signaling) properties towards K+ limitation, while these proteins exhibited enzymatic activities in vitro. The analysis of other chimeras such as KdpD-UspC or KdpD-UspA demonstrates that sensing/signaling was not prevented because of the replacement of the domain per se, but that the blockage of the sensor was specifically due to the insertion of UspF or UspG. These data suggest that the N-terminal cytoplasmic domain is important for KdpD/KdpE sensing and/or signaling.

Isolates that were indeterminate in one or more regions (n = 9) were excluded from this compilation. Figure 4 Summary of the vacA gene mosaic combinations based on amplicon sequencing

in 145 biopsies. Genotypes in the remaining 14 biopsies could not be established. N = number of strains; s1/s2, signal-sequence type; i1/i2 = intermediate region type; d1/d2 = deletion type; m1/m2 = mid-region type. In group 3, there were two isolates Gamma-secretase inhibitor (6%) derived from peptic ulcer patients, while in group 1 and 2 there were 20 isolates (24%) and eight isolates (27%), respectively, originating from ulcer patients. The lower frequency of peptic ulcer observed in vacA s1d1m1 genotype compared to other genotypes was not statistically significant. Eight biopsies from group 1 (10%) and two biopsies from group 2 (7%) were derived from patients with

atrophic gastritis, while in group three there was no subject with atrophic gastritis (not statistically significant). Intraindividual variations of cagA EPIYA and vacA genotypes in corpus, antrum and duodenal bulb In 51 of 71 individuals, Selleckchem p38 MAPK inhibitor biopsy specimens from all three locations of the stomach (corpus, antrum and duodenal bulb) were available for analysis. In 26 of these 51 subjects, the cagA and vacA genotypes were identical in all locations. Considering the remaining 25 subjects, 22 subjects differed with respect to the cagA EPIYA genotype, two with regard to the vacA (i) genotype, two considering

the vacA (d) genotype and one with respect to the vacA (m) genotype, when comparing the locations for each subject (Additional file 1). Discussion The results of several studies have indicated that Flavopiridol (Alvocidib) there is an association between the cagA gene and gastric cancer [14, 27, 28, 48]. There are also reports showing an association between the vacA gene and gastroduodenal sequelae (e.g. peptic ulcer, atrophic gastritis) of H. pylori infection [36, 38–40]. Here we show that of the individuals with biopsies from all locationsns (corpus, antrum and duodenal bulb), 49% had different cagA EPIYA genotype between the three locations. There is a possibility that these individuals may have been infected with different strains on different occasions. However, it is perhaps more likely those H. pylori strains acquired genetic alterations in cagA after infection. Three recombination mechanisms have been detected in the cagA gene; homologous recombination between CM sequences, recombination between EPIYA sequences or between short similar sequences [49]. These recombination mechanisms, as well as mutations in the gene, may serve as a driving force for generating strain diversity in H. pylori, also called microevolution [50]. It is possible that infection with multiple H.

Little is known about the promoter structures and transcriptional regulation of E. chaffeensis genes and their contributions to alter the gene expression in response to tick and vertebrate host cell environments. Promoter analysis under in vivo conditions is not possible at this time because of a lack of methods to transform E. chaffeensis. In the current study, we learn more report the first description of mapping promoter regions of two host-specific differentially expressed genes of E. chaffeensis. Results Primer extension analysis of p28-Omp genes 14

and 19 Host-specific differential protein expression from numerous E. chaffeensis genes, including from p28-Omp multi-gene locus, has been reported previously [18–20]. To evaluate the gene expression at transcription level, primer extension analysis was performed

for p28-Omp genes 14 and 19 with macrophage and tick cell-derived E. chaffeensis RNA (Figure 1A and 1B). The primer extended products for genes 14 and 19 were detected in tick cell- and macrophage-derived https://www.selleckchem.com/products/ly2606368.html E. chaffeensis RNA, respectively (Figure 1). The analysis also aided in identifying the transcription start sites for genes 14 and 19 located at 34 and 26 nucleotides upstream to the initiation codons, respectively (Figure 1). The nucleotide at the transcription start sites for both the genes is adenosine. Figure 1 Primer extension (PE) analysis of p28-Omp genes 14 and 19. Panel A has Elongation factor 2 kinase a cartoon spanning all 22 genes [37]. This panel also has an expansion of cartoons for genes 14 and 19 with predicted transcripts, the primers used for the PE analysis and sequences of the primer extended products with transcription start sites identified with asterisks. PE analysis products resolved on a sequencing gel are shown in panel B. Blots on the left and right represent the data for transcripts of genes 14 and 19, respectively. A sequence ladder for the gene 14 analysis

was prepared by using the same primer used for the PE analysis but with a DNA template spanning the gene 14 sequence. For gene 19, PE analysis was performed with RRG 44 primer, and the sequencing ladder was generated by using RRG20-PEXT primer with a gene 19 DNA template. (Lane 1, E. chaffeensis RNA from tick cells; lane 2, E. chaffeensis RNA from macrophages). Transcriptional analysis by quantitative RT-PCR at different times post-infection Our previous studies suggested that both p28-Omp genes 14 and 19 are transcriptionally active in E. chaffeensis originating from vertebrate macrophages and tick cells but the expression levels are different [9, 19]. The quantitative gene expression differences for genes 14 and 19 were determined by TaqMan-based real-time RT-PCR analysis (quantitative RT-PCR) (Figure 2). Consistent with the previous observations, transcripts for genes 14 and 19 were detected in RNA isolated from both host cell backgrounds. In tick cell-derived E.

9 months (HT ≥ grade 2, n = 15) for those on BAY-BEV (Figure 1B). Development of HT was not related to survival following sorafenib without bevacizumab (BAY-NSCLC and BAY-CRC; P > 0.19), with a single exception where

patients on BAY-CRPC with < grade 2 HT (n = 37) actually had marginally non-significantly prolonged survival when compared to those individuals with HT ≥ grade 2 (n = 9; 1.8 versus 3.6 months respectively; P = 0.067). Figure 1 Kaplan-Meier curve of progression-free survival following treatment with bevacizumab in combination with docetaxel and thalidomide, n = 60 (A) , or bevacizumab in combination with sorafenib, n = 27 (B) , or sorafenib alone or in combination with bevacizumab, or cetuximab in patients with prostate cancer, various solid tumors, colon cancer, or NSCLC n = 113 (C) , or overall survival following treatment click here with bevacizumab

in combination with sorafenib, n = 26 (D) versus development of ≥ Grade 2 toxicity – - or < Grade 2 toxicity ------ as indicated on each respective figure. Respective P = 0.0009, P = 0.052, P = 0.0003, and P = 0.0068 by a two-tailed log-rank test. As is indicated in Table 1, incidence of ≥ grade 2 HFSR was also associated with PFS in patients with colon cancer treated with sorafenib (P = 0.0065) with those patients having HFSR (n = 2) having a significantly longer response to sorafenib (8.7 months) than those without HFSR (4.7 months, learn more n = 16). HFSR and PFS were either marginally not associated in patients on BAY-BEV (P = 0.094), or were

not associated on BAY-NSCLC and BAY-CRPC (P ≥ 0.29). However, since each group treated with sorafenib had a similar trend (i.e. patients with HFSR always had a longer median PFS) with a small number this website of patients in each group (n ≤ 46), we pooled survival data obtained from the above trials to analyze the relationship between HFSR and PFS with greater statistical power. The pooled analysis significantly improved the relationship between PFS and HFSR with patients who developed HFSR following treatment with sorafenib, either as single agent or in combination with bevacizumab or cetuximab (n = 32), having a median PFS of 6.1 months compared with 3.6 months in patients without these toxicities (n = 81; P = 0.0003, Figure 1C). However, this pooled analysis should be interpreted with caution given that it is present only when heterogeneous groups of data obtained from patients are combined together. Association of these toxicities with OS was not significant with a single striking exception where those patients receiving the BAY-BEV combination had a significantly longer survival (P = 0.0093) if they developed hypertension during therapy (29 months, n = 14) when compared to those that did not develop hypertension (5.7 months, n = 12; Figure 1D). No other toxicity (i.e., rash/desquamation, diarrhea, or fatigue) was related to PFS (P > 0.05) for either drug.

The natural history

of these patients is unclear, as they are generally on anticoagulants, but we can glean some estimate of risk from studies that have evaluated temporarily discontinuing anticoagulation after intracranial hemorrhage. It appears safe to discontinue anticoagulation for brief periods of time [14, 15]. Most of this work has been BMN 673 in vitro conducted in patients with spontaneous intracranial hemorrhage. It is possible that traumatic hemorrhage is a different entity, as injured patients are more hypercoaguable than then general population. Our data represents an important adjunct to these studies, in that we have demonstrated that early reintroduction of anticoagulation can be safely accomplished. There are limitations of this study worth noting. We did not have a protocolized approach to management of anticoagulation. Rather, we consulted with the neurosurgeons on a daily basis and we started anticoagulation when their clinical judgment indicated it was safe to do so. As such, we are likely dealing with a highly select patient population. Additionally, our sample size is limited. It is possible that we would have yielded different results with a larger sample size. Finally, some of our patients received anticoagulation for Erismodegib clinical trial uncomplicated

PE rather than the extreme examples listed in this discussion. This does not detract from our results demonstrating safety of anticoagulation, however. In conclusion, selected patients with brain injury may safely be anticoagulated to prevent the propagation of thrombotic Monoiodotyrosine complications. Our data does not provide definitive evidence of the safety profile. Rather, this manuscript provides initial evidence that suggests that traditional beliefs about anticoagulation

in patients with brain injuries may be incorrect. Our data should be used a springboard to develop further study on this issue, so that the specific groups that would most benefit from anticoagulation could be defined. References 1. Geerts WH, Code KI, Jay RM, Chen E, Szalai JP: A prospective study of venous thromboembolism after major trauma. N Engl J Med 1994,331(24):1601–1606.PubMedCrossRef 2. Norwood SH, Berne JD, Rowe SA, Villarreal DH, Ledlie JT: Early venous thromboembolism prophylaxis with enoxaparin in patients with blunt traumatic brain injury. J Trauma 2008,65(5):1021–1026. discussion 6–7PubMedCrossRef 3. Bates SM, Ginsberg JS: Clinical practice. Treatment of deep-vein thrombosis. N Engl J Med 2004,351(3):268–277.PubMedCrossRef 4. Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA, et al.: Prevention of venous thromboembolism. Chest 2001,119(1 Suppl):132S-175S.PubMedCrossRef 5. Knudson MM, Morabito D, Paiement GD, Shackleford S: Use of low molecular weight heparin in preventing thromboembolism in trauma patients. J Trauma 1996,41(3):446–459.PubMedCrossRef 6.

The concentration of butyrate we used is well within the concentrations known to occur in the lumen of the lower gastrointestinal tract [37]. Figure  2C shows that zinc at 0.1 to 0.5 mM significantly protected cells from the drop in TER inflicted by XO + 400 μM hypoxanthine. Likewise, Figure  2D shows that 0.1 to 0.3 mM zinc, but not 0.4 mM zinc,

reduced Stx2 translocation triggered by XO + 400 µM hypoxanthine. Thus, while Figure  2C did not show the arch shape seen in Figure  1C, Figure  2D does have the “U” shape similar to that seen in Figure  1D with hydrogen peroxide as the injuring oxidant. In monolayers treated with hypoxanthine + XO, the amount of Stx2 that translocated across the monolayer in 24 h was 8.5 ± 3.0% (mean ± SD

of 5 experiments) of the total amount added to the upper chamber. find more Figures  1 and 2 showed that zinc acetate could protect against oxidant-induced drop in TER, a measure of intestinal barrier function, and inhibit the translocation of Stx2 Cabozantinib ic50 across T84 cell monolayers as well. Figure 2 Effect of hypoxanthine plus xanthine oxidase on barrier function and Stx2 translocation in T84 cells. Panels A-C show effects on TER, while Panel D shows effect on Stx2 translocation. The “standard” concentration of hypoxanthine was 400 μM if not otherwise stated, and the standard concentration of XO was 1 U/mL. Panel A, effect of Olopatadine various concentrations of hypoxanthine on TER. The “zero” hypoxanthine condition received 1% DMSO vehicle alone. Panel B, additive effect of zinc with butyrate on TER. Panel C, protection by zinc against the drop in TER induced by hypoxanthine plus XO. Panel D, protection by zinc against Stx2 translocation triggered by hypoxanthine plus xanthine oxidase. In Figure  3 we examined the effects of other metals on TER and Stx2 translocation. We focused on the transition metals nearest to zinc in atomic number, including manganese, iron, nickel, and copper. Figure  3A shows the effects of two of these metals on TER, while Panels B-D show

the effects on Stx2 translocation. Figure  3A shows that in contrast to zinc (top curve), FeSO4 and MnCl2 had no protective effect against the drop in TER triggered by XO + hypoxanthine. Copper (as CuSO4) also failed to protect against the drop in TER (data not shown). When Stx2 translocation was measured, FeSO4 seemed to slightly enhance Stx2 translocation triggered by H2O2 (Figure  3B), but this did not reach statistical significance. Nevertheless, iron has been shown to be able to potentiate oxidant-induced damage, and this has often been attributed to iron’s ability to catalyze the Fenton reaction, in which H2O2 is split into 2 molecules of hydroxyl radical (HO•). Figure  3C shows that manganese (as MnCl2) failed to protect against Stx22 translocation, and at 0.