Serum HBV DNA and ALT levels were measured every 3 months after entecavir treatment began. Virologic response (VR) was defined as undetectable serum HBV DNA by real-time PCR assay (<60 IU/mL).3,22 more Enzyme-linked immunosorbent assay was used to test HBeAg state. Statistical analysis Continuous variables which did not show normal distribution were expressed as the median with range. Differences in baseline characteristics between the patient group with or without HBeAg and VR were analyzed using Student t-test or Mann-Whitney rank sum test for continuous variables and the ��2 test for categorical variables. Pearson’s correlation coefficient was tested for correlation between two variables.

Area under the receiver operating characteristic (ROC) curve was calculated as previously reported23 to assess the predictive value of pre-treatment variables for VR using Medicalc version 11 (Medicalc software, Mariakerke, Belgium). A two-tailed P-value <0.05 was considered statistically significant. RESULTS Clinical characteristics Fifty two treatment-na?ve chronic hepatitis B patients were enrolled during the study period, and six patients were lost to follow up after 6 months of entecavir therapy. The median duration of treatment was 26 months (range: 7-35 months). The baseline characteristics of these patients are summarized in Table 1. The baseline HBV DNA levels were significantly higher in the HBeAg-positive group than in the HBeAg-negative group (P=0.001). The HBsAg levels were similar between HBeAg-positive and negative groups.

However, the ratio of baseline HBsAg titer to HBV DNA level (“HBsAg/HBV DNA ratio”, log10 [HBsAg]/log10 [HBV DNA]) was significantly higher in the HBeAg-negative patients (P=0.01). Table 1 Baseline characteristics of the patients Virologic response to entecavir therapy and predictors At 3,6,12 and 24 months, cumulative virologic response rates were 40.0%, 71.2%, 81.5%, and 88.0%, respectively (Fig. 1). When baseline characteristics were compared according to VR, VR (+) group showed significantly lower HBV DNA levels and higher HBsAg/HBV DNA ratio (P=0.013, 0.001, respectively; Table 2). However, HBsAg levels were not significantly different between VR (+) and VR (-) groups (P=0.278; Table 2). Univariate analysis showed that the VR rate was significantly higher in HBeAg-negative patients (55%, 85% and 95% at 3,6 and 12 months, respectively) compared to that in HBeAg-positive patients (34.

4%, 62.5% and 76.1% at 3,6 and 12 months, respectively; P=0.043; Fig. 2A). Gender, presence of cirrhosis, and ALT level were not significant predictors of VR (P=0.223, 0.261, 0.39, respectively; Fig. 2B-D), whereas low pre-treatment serum HBV DNA level was associated with higher VR, although the statistical significance was marginal (P=0.059, Fig. 2F). The HBsAg/HBV AV-951 DNA ratio categorized by the cut-off value of 0.

An alterative pathophysiological mechanism other than the toxin production of K. oxytoca in inducing colitis cannot be ruled out by this study. However, taken together with the typical histological features of toxin-induced colitis seen in AAHC and in colitis induced by K. oxytoca in animal models of this disease (10), citation the current results support the hypothesis that the K. oxytoca cytotoxin is associated with AAHC. Future studies need to clarify this issue. Cytotoxic effects of K. oxytoca isolates from AAHC patients were reported previously (1, 8, 10, 15-17). To date, however, those reports were not extended to include other Klebsiella species or K. oxytoca strains from infections of other organs.

An important finding of the current study was that the majority of toxin-positive strains were obtained from stool cultures regardless of whether they were isolated from symptomatic or asymptomatic carriers. Accordingly, we propose that K. oxytoca should not be viewed as a naive constituent of the normal bowel microflora, in contrast to other Klebsiella species. Given its capacity to induce AAHC, resident K. oxytoca should be classified as an opportunistic pathogen that is able to induce disease under certain circumstances, such as an alteration of the normal colonic microflora due to antibiotic treatment and the subsequent overgrowth of the toxin-producing bacterium (5). This proposal is supported by the finding that despite the fact that a high proportion of isolates originating from asymptomatic carriers showed cytotoxicity, their amounts in stools were significantly lower than amounts in stools from symptomatic patients (<101 CFU/ml compared to 4 �� 106 CFU/ml for AAHC patients) (23).

The coresidence of toxin-positive and toxin-negative isolates in patients and in healthy individuals is consistent with the hypothesis that colitis may result from toxin production during the outgrowth of these strains following antibiotic treatment. Moreover, for the patient group with acute or chronic diarrheal diseases, more than half of the isolates were cytotoxin positive. Thus, the role of cytotoxin-producing K. oxytoca in intestinal disease other than AAHC will require further investigation (23). Interestingly, cytotoxicity was also detected for a large proportion of skin isolates, which were derived primarily from foot ulcers.

These wound infections are thought to be derived via fecal contamination Drug_discovery (2). None of the isolates originating from typical Klebsiella infection sites, i.e., the urinary and respiratory tracts, showed a cytotoxic phenotype. Two isolates from bloodstream infections were cytotoxin positive: one was isolated from a patient with CRBSI, and the second was obtained from a patient with cholangitis. It is reasonable to propose that the origin of these infection-causing strains was the skin or intestine. In summary, we found that cytotoxin-positive K.

Thus, it is interesting to discuss the virological advantages disposing this genotype A isolate to become the major player in HBV/HIV-1 coinfection among MSM. One such advantage might be the higher progression rate (16 to 23%) to chronicity of genotype A than of genotype C (28, 30), enhancing its capacity to serve as a source of new infections. As 9 of 26 genotype A-infected patients (35%) http://www.selleckchem.com/products/Y-27632.html were HBcAg IgM positive and 2 had acute hepatitis, it is obvious that genotype A infections are actively ongoing among the MSM population. Though further studies are needed, considering the tMRCA of the prevailing strain A2, the younger age of patients infected with this strain than of those infected with other genotypes, and its high prevalence among MSM, this strain may have acquired higher infectivity and efficient transmission through sexual contact.

Another issue we wanted to clarify in this study was the transmission of antiviral drug resistance. We found no antiretroviral resistance in the 26 sequenced cases. On the other hand, we detected two cases with a mutation combination of rtV173L + rtL180M + rtM204V in HBV reverse transcriptase, demonstrating resistance against lamivudine-emtricitabine. One patient was antiretroviral therapy na?ve; thus, transmission of drug-resistant HBV is strongly suspected. It is peculiar that the isolate harboring the drug-resistant mutations in HBV was a singleton, considering that genetically identical isolates were prevailing, that there were very low mutation rates that suggest few chances of reverting to wild type, and that there were actively ongoing de novo infections.

This finding might be due to resistant viruses being masked by wild-type viruses under untreated conditions, as reported in the case of HIV-1 drug resistance (6). The possibility of minority resistance populations of HBV could be verified by detection with a highly sensitive method. In conclusion, we clarified the molecular epidemiology of HBV/HIV-1 coinfection in Japan. Our data suggest that ongoing HBV infections lie outside prevention programs targeting the MTCT and blood transfusion infection routes, and they suggest the urgent need for new prevention strategies focusing on the high-risk group of the HIV-1-seropositive MSM population. ACKNOWLEDGMENTS This study was supported by a Research Grant for Research on HIV/AIDS from the Ministry of Health, Labor, and Welfare of Japan (no.

H19-AIDS-007, H21-AIDS-005, and H22-AIDS-004). We thank Yasuhito Tanaka, Nagoya City University Graduate School of Medical Sciences, for helpful discussion Batimastat and Claire Baldwin for help in preparing the manuscript. Footnotes Published ahead of print on 19 January 2011.
nonalcoholic fatty liver disease (NAFLD) is an increasingly common cause of liver disease that can progress to nonalcoholic steatohepatitis (NASH) and culminate in end-stage liver disease, featuring liver damage with fibrosis and cirrhosis (1, 10, 36). The pathogenesis of NAFLD/NASH is poorly understood.

94%, female 7.2%).[16] All cases were over five years, (range 5 to 17 years) during the period from September to November, 2006. A retrospective cohort study was carried out by door to door search for the children in the age group of 10 months to 17 years in the case block only. Data on children selleck chem vaccination status were collected by interviewing the mothers, reviewing health records, and verifying with vaccination cards. In sub centre Sailli, attack rates of measles by age and vaccination status indicated 16 case patients of 56 non-immunized (28.6%) compared to 35 case patients of 790 immunized (4.4%) children and it was statistically significant. (Relative risk (RR): 6.44%; 95% C.I.: 3.81�C10.91 P < 0.001). The proportion of the children vaccinated was 93.3%.

The calculation of vaccine efficacy among those exposed to the vaccine yielded an estimate of 84.4% [Table 1]. Table 1 Attack rates of measles by age and vaccination status in villages of Shahpur block, district Kangra, Himachal Pradesh, India, 2006 In sub centre Sarah, attack rates of measles by age and vaccination status indicated four cases out of 22 non-immunized (18.18%) compared to 14 cases out of 408 immunized (3.43%) children and it was statistically significant. (RR: 5.3; 95% CI: 1.90 �C 14.77; P < 0.001). The calculation of vaccine efficacy yielded an estimate of 81.13% when children under 10 months of age and the previous history of measles were excluded [Table 2]. The vaccine efficacy for Nagrota Bagwan block could not be calculated, as there was no outbreak in the area.

Table 2 Attack rates of measles by age and vaccination status in villages of Shahpur block, district Kangra, Himachal Pradesh, India, 2006 Cold chain maintenance and its equipments were assessed by checking availability of refrigerator, ice liner, deep freezer, vaccine carriers in both case and control areas. Ice Liner Refrigerator (ILR), deep freezers, and vaccine carriers were physically present in sufficient numbers and were in the working conditions in both study areas. On observation in the case area, the practice of maintaining the temperature record on ILR and deep freezers was not carried out in twice a day schedule as per program recommendations while the control area was noticed to be normal. Thermometers and the temperature registers were available in both case and control areas. Both case and control areas have adequate supply of pressure cookers, stoves, sterilizers, kerosene, vaccine carrier boxes, and icepacks. Health care provider-related issues All eight workers in both blocks could correctly list Batimastat the six vaccine preventable diseases (VPDs) and could also correctly state the national immunization schedule for children 0�C59 months old.

However, the limited number of samples from healthy subjects and the impact of subject-specificity on the overall variation between samples hamper a more detailed comparison between ileostomy effluent and small intestinal lumen samples. Figure 1 (a) Relative contribution of different microbial groups that Paclitaxel clinical are present in samples derived from the small intestine and feces of four and two healthy individuals, respectively, and those from five healthy ileostomists. The taxonomic classification is … Microbiome of small intestine is less complex than that of the colon To obtain insight into the genetic potential and population dynamics within the small intestinal microbiota, a metagenomic library was constructed from the ileostoma effluent from a healthy individual who had the stoma for more than 20 years and did not require any stoma-related medication.

As the ileostomy effluent microbiota composition fluctuates over time (Booijink et al., 2010), the metagenome library was constructed on four different morning and afternoon effluent samples. The entire library encompassed 25344 fosmid clones with an average insert size of more than 25000bp, and thus, containing in total more than 700Mb (Supplementary Table S1). After initial quality control (see Supplementary Materials), three libraries representing the morning (1M) and afternoon (1A) of the same day and a morning sample taken 1 year earlier (A) were subjected to end sequencing (Sanger) and GS-FLX random sequencing (Supplementary Table S1), generating a total of 178Mb of sequence information.

146Mb of sequence information could be assembled into contigs that collectively encompass 63Mb, with the largest contig being 78kb, and leaving only 13% of the sequence-reads unassembled. This assembled proportion of sequences is considerably higher than previously observed with fecal metagenomes (Gill et al., 2006; Kurokawa et al., 2007), indicating a lower species diversity in the small intestine as compared with the colon, which is in line with the previous observations based on 16S rRNA genes (Hartman et al., 2009; Booijink et al., 2010). More than 170000 genes could be assigned in the assembled contigs, of which 16% was complete. Microbiome of the small intestine consists of various microbial phyla Phylogenetic positioning of sequences suggested that they originated from a wide variety of phylotypes, with Clostridium sp.

, Streptococcus sp. and coliforms as dominant phylogenetic groups (Supplementary Figure S1), which is consistent with the 16S rRNA-based analyses. In addition, an unexpectedly large fraction of high G+C Gram positives Batimastat was observed, which may be due to the commonly encountered underestimation of these microbial groups by regular 16S rRNA gene amplification (Hayashi et al., 2004).

Sporadic CRC cases and controls were matched for age, sex, smoking and drinking history. Table 1 Clinical characteristics of the CRC patients and normal controls The study inhibitor was approved by the Institutional Review Boards of the Drum Tower Hospital. All the participants provided written informed consent at the time of recruitment and agreed to blood collection. DNA extraction Peripheral venous blood (5 mL) was drawn from each subject before they received surgery or chemotherapy, and was placed in tubes containing EDTA and stored at -70��C until analysis. Total genomic DNA was extracted using a purification kit (Promega, Madison, WI, USA) according to the manufacturer��s instructions. Genotyping analysis The CDH1 -347G��GA polymorphism was genotyped by the PCR-RFLP method.

A 447-bp fragment containing the -347G��GA polymorphism in the CDH1 promoter was amplified with the following primers: forward, 5′-GCCCCGACTTGTCTCTCTAC-3′; reverse, 5′-GGCCACAGCCAATCAGCA-3′. PCR amplification was carried out in a volume of 25 ��L containing 20 ng of genomic DNA, 1 ��L of primers, 20 ��mol/L each of the forward and reverse primers, 2.5 ��L of 10 �� PCR buffer (Mg2+-free), 2 ��L of dNTP, 1.5 ��L of MgCl2 and 0.5 U of Taq polymerase (TaKaRa Biotechnology, Dalian, China). The amplification was performed in a programmable thermal cycler (MWG Biotech AG, Ebersberg, Germany) as follows: 1 cycle of 95��C for 2 min; 35 cycles of 94��C for 1 min, 61��C for 1 min and 72��C for 1 min; and a final cycle of 72��C for 10 min. The PCR product was digested with BanII (TaKaRa Biotechnology) at 37��C overnight (Figure (Figure1A1A and andB).

B). After digestion, the products were separated by 3% agarose gel electrophoresis and stained with ethidium bromide (Figure (Figure1C).1C). GA/GA homozygous cases were represented by DNA bands of 332 and 116 bp. G/G homozygous cases were represented by DNA bands of 263, 116 and 68 bp. GA/G heterozygous cases displayed a combination of both alleles (332, 263, 116 and 68 bp). Figure 1 Genotyping analysis of the CDH1 -347G��GA polymorphism by PCR-RFLP analysis. A: Structural diagram of the restriction enzyme analysis for BanII; B: Schematic overview of the E-cadherin gene promoter PCR fragment and the locations of the BanII restriction … Immunohistochemistry CRC tissue samples were collected from CRC patients who underwent surgery.

Normal colon tissue samples were collected from outpatients via colonic biopsies during colonoscopy examination. Immunohistochemistry was carried out using the avidin-biotin-peroxidase complex method. The central region of CRC tissue samples and normal colon AV-951 tissue samples were cut into 4-��m sections, mounted on glass slides, deparaffinized and rehydrated by xylene and graded ethanol solutions. Endogenous peroxidase activity was blocked by incubation with 3% hydrogen peroxide for 20 min at room temperature.

Figure 6 11a induces G1/S phase cell cycle arrest in a time dependent selleck bio manner in HCT116 isogenic cell lines. Figure 7 11a induces G1/S phase cell cycle arrest in a dose dependent manner in HCT116 isogenic cell lines. Discussion In this study, we evaluated the dependency of 11a cytotoxicity on PNR expression and further investigated the mechanism of 11a cellular cytotoxicity using various cell-based assays. Although 11a was originally reported as a synthetic agonist for PNR, it was found not to be a direct PNR agonist in the recently developed TR-FRET assay which measured PNR-RetCoR dissociation [32]. Consistent with this finding, our cell-based assays similarly showed that 11a was unlikely to be a direct agonist for PNR.

We employed luciferase reporter assays to compare the ability of 11a to activate different subfamily II nuclear receptors, of which PNR is a member [36]. However, our results showed that 11a is least potent in PNR activation, whereas 11a could weakly activate other members of subfamily II such as TLX, COUP-TFI and COUP-TFII at the different concentrations tested. Further studies using stable cell lines overexpressing PNR confirmed that the 11a-induced cytotoxic effects are PNR independent. Together, our results indicate that 11a may have cellular targets other than PNR to confer cytotoxic effects. Although the cellular targets of 11a remain to be determined, 11a was found to activate COUP-TFII in DR2-luciferase reporter assay and COUP-TFII target genes in two breast cancer cell lines. The only other known weak agonist for COUP-TFII is atRA [44].

atRA was shown to activate COUP-TFII on the NGFI-A promoter in the luciferase reporter assay [44]. Induction of RARB2 by atRA causes growth inhibition and apoptosis in cancer cells and this process requires the orphan nuclear receptor COUP-TFII [42]. Since 11a activated COUP-TFII in the DR2 luciferase assay (Figure 1B) and induced RARB2 and NGFI-A gene expression to a comparable level as atRA (Figure S3), it is possible that 11a could serve as an agonist for COUP-TFII and substitute atRA in some cancer treatment. For example, all-trans retinoic acid has long been used for the treatment of acute promyelocytic leukemia (APL) and were shown to inhibit solid tumor growth [55], however, the strong cytotoxicity prevents its wide use in cancer treatment. The concentrations of RAs required for activation of COUP-TFII are 10-100 times higher than the physiological levels [44], on the contrary, 11a at 10-time lower concentration could manifest the same effect in the COUP-TFII target gene activation (Figure 3). Whether 11a-induced cytotoxicity is at least in part mediated through COUP-TFII Anacetrapib is worth further investigation.

In contrast, the ECCDS did not demonstrate efficacy for sulfasalazine 3 g/d alone, but only in combination with 6-methylprednisolone[4]. Subsequently, newer mesalamine agents have been evaluated in clinical trials for CD. In the largest of these studies selleck products (n = 310), patients with active ileal or ileocolonic CD were randomized to receive Pentasa?, 1, 2 or 4 g/d or placebo. The 4 g/d group experienced a greater decrease in CDAI than the placebo group (72 vs 21 points, P < 0.01), an effect more pronounced in isolated ileal disease, and remission was achieved in 43% vs 18% respectively[5]. Subsequently, two similarly designed trials described in a meta-analysis failed to replicate these findings although there was an overall statistical benefit for the 4 g dose of mesalamine that was of questionable clinical significance[6,7].

Several other trials also have demonstrated benefit for mesalamine in CD, but the quality of the trials was less robust[8,9]. When compared to other agents in controlled trials approximately 40%-55% of patients treated with mesalamine 4 g/d achieve remissions but the efficacy was less than budesonide (9 mg/d) for the induction of remission at both 8 wk (45% vs 65%, P = 0.001) and 16 wk (36% vs 62%, P < 0.001)[10] and comparable to ciprofloxacin 1 g/d[11]. Maintenance after medical remission Sulfasalazine at reduced doses compared to the induction phase provided no benefit compared to placebo in the maintenance phase of the NCCDS and ECCDS, nor in a smaller study[3,4,12].

Gisbert et al have reviewed nine randomized placebo-controlled studies of mesalamine as a maintenance agent, four of which showed a significantly decreased risk of relapse compared to placebo, although there was great heterogeneity in formulation, dosage, duration of treatment, and disease location[13]. Further, a Cochrane review of seven randomized placebo-controlled trials concluded that treatment with 5-ASA agents for at least six months did not confer an advantage over placebo in patients with medically-induced remission[14]. When initiated within three AV-951 months of a medically-induced remission, mesalamine (2 g bid), in contrast to placebo, prevented more relapses over a two year period[15]. In the context of a steroid-induced remission, short-term weaning from steroids may be slightly facilitated with mesalamine 4 g/d, but there was no benefit at one year in relapse rate between patients maintained on mesalamine compared with placebo[16]. Post-operative maintenance The natural history of CD after ileocolonic resection is variable, and may be influenced by such factors as pattern, extent, and duration of disease preoperatively as well as smoking history.

2). All patients were admitted to the ICU after operation as per our department /Tottori University protocol. The patients were discharged from the ICU when stable according our critical care departmental sellckchem criteria. Table 1 Patient Demographics in ICU After Surgical Treatment of Esophageal Cancer Table 2 Gene Expression Data for Esophageal Cancer Patients in the ICU After POD 14 We measured serum mRNA levels for 14 days postoperatively. Informed consent was obtained from each patient and study protocols followed standard ethical guidelines (Declaration of Helsinki, 1975) and were approved by the institutional review board of Tottori University (approval no.138, no 138 1, 2001; no. 343, 2009). The patients consisted of 3 females (mean age 67.3 years, age range 49 to 82 years) and 24 males (mean age 65 years, age range 40-76).

All patients were classified as American Society of Anesthesiologists (ASA) physical status 1 or 2. Patients were prospectively followed for 12 months postoperatively. SIRS or ARDS were diagnosed according to accepted consensus definitions [41,42]. Clinicopathological findings, such as age, diagnosis, etiology, prognosis, effect of the neutrophil elastase inhibitor sivelestat (4.8 mg/kg/day), total days of ventilator dependence (DVD), total days of ICU stay, preoperative CRP levels (preCRP), CRP levels at postoperative day (POD) 1, peak concentrations of CRP (peak CRP), operation duration, anesthesia duration, PaO2/FiO2 ratio at POD 1, days of SIRS, sequential organ failure assessment (SOFA) scores at POD 1, and mortality at 30 days, 6 months, and 1 year were recorded.

Anesthesia consisted of general anesthesia and epidural anesthesia. After surgery, all patients were reintubated with single-lumen endotracheal tubes from the double-lumen endotracheal tubes used intraoperatively and received ventilator support in ICU. Serum from whole blood was obtained intraoperatively and on POD 1, POD 3, POD 5 and POD 14. We measured serum mRNA levels of 11 genes (MMP9, CRP, HMGB1, MUC1, EGR1, PBEF1, PDGFA, TGF-��1, TNF-��, VWF, and IL-6). Sivelestat was prophylactically administered intravenously by the judgment of the attending physician and according to the manufacturer’s recommendations. We distinguished SIRS from severe non-infectious systemic inflammatory response syndrome (SNISIRS) by examining gene expression (GE) in the serum and synchronizing GE changes with the clinical course of events. Processing of the blood and serum samples was performed after blood Batimastat sampling during the operation and at POD 1, POD 3, POD 5 and POD 14. mRNA quantification was performed as previously described [43]. RNA extraction and real-time RT-PCR RNA was performed after DNase treatment, also reported previously [43-45].

Further details about data processing and quality control selleck steps can be found in Supplemental Methods. Taxonomic classification was made using the Ribosomal Database Project na?ve Bayesian classifier (Wang et al., 2007). Rarefaction curves, alpha diversity metrics and UniFrac distances (Lozupone and Knight, 2005) calculated using QIIME (Caporaso et al., 2010) employed re-sampling (bootstrapping and jackknifing: 1000 re-samples) at below the size of the smallest library to avoid sample size-based artifacts (Lozupone et al., 2011). Relative abundance correlation between pairs of phylotypes detected in at least two samples was performed in MATLAB (MathWorks, Natick, MA, USA) by calculating the Pearson correlation coefficient using amplicon libraries produced from lumen DNA.

This analysis was also conducted with phylotypes divided into taxonomic families based on the results of the Ribosomal Database Project na?ve Bayesian classifier. Non-parametric permutational multivariate analysis of variance (perMANOVA) was conducted using the ��vegan’ package (Oksanen et al., 2010) was performed using the ��indicspecies’ package in R (De C��ceres and Legendre, 2009). The indicator species analysis determines the strength of the association between a phylotype and a condition and considers the relative frequency and abundance of phylotypes in target versus non-target conditions (De C��ceres and Legendre, 2009). To focus on dominant indicators, indicator phylotypes were selected that (1) were significantly associated with DSS-treated or healthy mice using indicator species analysis or correlation analysis (P<0.

05), and (2) had an arithmetic average difference of >0.5% relative abundance between healthy and DSS-treated mice. Genotype-insensitive as well as genotype-sensitive (that is, specific to either wt or STAT1?/?) indicator phylotypes were identified in separate analyses using data from DNA and cDNA templates. Representative indicator phylotype sequences were added to a bootstrapped RAxML phylogenetic tree as described in Supplemental Methods. Metatranscriptomic data analysis Metatranscriptomic sequencing data were analyzed following the double RNA analysis pipeline described by Urich et al. (2008). Briefly, rRNA tags present in non-rRNA depleted samples (IDs 1, 6, 8, 9 Supplementalry Table S1) were taxonomically binned using MEGAN (Huson et al.

, 2007) and a custom reference database of small subunit rRNA sequences (Urich et al., 2008). mRNA tags were compared against the NCBI non-redundant database using BlastX and taxonomically classified using MEGAN. Multiple mRNA libraries from the same condition were combined (wt control: IDs Carfilzomib 1�C5, wt DSS: IDs 6 and 7) (Supplementary Table S1 and S5). SEED categories were assigned using the MG-RAST Server (Version 2, significance threshold: E-value 10?5) (Meyer et al., 2008).