This retrospective review does not suggest a preferred regimen with which to combine bevacizumab, and future results of new phase III trials are needed to address this question. The factors associated with improved OS on multivariate analysis were use of maintenance therapy and female sex. Subgroup analysis of the AVAiL trial also showed a better prognosis for female patients exposed to bevacizumab, but the E4599 study suggested the opposite,

i.e. better outcomes for male patients than for female patients (HR for OS 0.70 [95% CI 0.57–0.87] vs 0.98 [95% CI 0.77–1.25], respectively). In the analysis reported herein, the median age of the sample used for OS estimation was adopted as a marker of age division (specifically, 62.9 years). This does not mean that we classified patients above that age as elderly; rather, we explored differences in outcomes comparing selleckchem both percentiles of age distribution. In this analysis, we were not able

to detect any influence of age on survival outcomes. With respect to the maintenance therapy advantage, patients who were able to initiate this phase were nonprogressors, and it was expected that they learn more would have better survival than patients not receiving maintenance therapy, considering that the majority of patients did not initiate maintenance therapy because of tumor progression. Although our analysis did not compare use of maintenance therapy between nonprogressor patients to better analyze the value of this treatment, the median OS of these patients reported here (22.7 months) suggests that this strategy can offer an extended period of disease control for these patients, as has previously been demonstrated by phase III trials.[16,17] Given the limitations of our analysis, we cannot conclude that the use of maintenance therapy was responsible for greater OS in our

series of patients entering the maintenance phase. In addition, because of the limitations of our sample SPTLC1 size, we combined patients receiving bevacizumab as a single agent and those receiving it in combination with pemetrexed as maintenance therapy, which precludes any suggestion regarding specific regimens. Our safety results did not reveal any new safety signal, and the outcomes were consistent with those reported previously. The frequency of hypertension, which was the most frequent AESI, can be considered lower than those reported in the literature, considering both all-grade and high-grade events.[18] Arterial and venous thromboembolic events were the most frequent high-grade AESIs. According to meta-analyses, the overall incidence of arterial events during bevacizumab treatment is 2.6%[19] and that of high-grade venous thromboembolic episodes is 6.3%;[20] both are similar to our findings. Although the incidence of high-grade neutropenia in our study was higher than that in the SAiL trial[8] (23.

Due to the comparatively high number of tank water samples testing positive for F. psychrophilum observed in the first subset of samples examined, we decided to screen all 2010 tank samples. Of the 85 tank water samples collected in 2010, however, only 8 (10%) were positive (range: 43 to 3,000 cells/ml) (Table 2). Table 2 Origin and percent of samples positive to F. psychrophilum   Origin

No. of samples % Positive for F. psychrophilum % of samples quantified Cells/ml Inlet and tank 2009           Inlets Ticino fish farms 60 7% 1.6% 73 to 1.5 × 104 Tanks Ticino fish farms 60 53% 1.6% 42 to 3.5 × 104 2010           Tanks Swiss fish farms 85 10% 0% 43 to 3’000 Healthy carriers 2011, 2012 Swiss fish farms 43 MK-0457 80% 0% 0-400 In contrast to culture or FISH, F.

psychrophilum was detected in healthy and quantified in infected fish by qPCR. F. psychrophilum densities in healthy individuals were well below the QL, in a range of 0 to 15,000 cells per spleen, whereas spleens from diseased fish contained bacterial densities over the QL, in a range of 7,000 to 7.7 × 108 cells per spleen. Positive results by qPCR were reported for all spleens originating from the 4 outbreaks; FISH allowed detecting F. psychrophilum in all outbreaks while culture showed F. psychrophilum only in 3 outbreaks. Risk factors We could not show any clear correlation between the presence of F. psychrophilum and selleck chemicals the environmental parameters measured. We observed that the F. psychrophilum densities tended to increase and to cause outbreaks after changes Thymidylate synthase in water parameters. For instance, a change in more than one ecological parameter tended to correlate with an outbreak or at least an increase of the number of F. psychrophilum in water (Figure 4). This observation, however, cannot be supported by any statistical analysis, because too few outbreaks could be analyzed during the

study period. Figure 4 Seasonal variation example. Physicochemical parameters [primary y axis: temperature (T in °C), pH of water, oxygen concentration (mg/L); secondary y axis: conductibility (μ Siemens)] measured in a selected fish farm (Ticino, Switzerland) during 2009. Detection of the pathogen in the tank water samples started on 9 June 2009 (*), the arrows indicate a flavobacteriosis outbreak in brown trout fario. Discussion This study shows that the qPCR assay developed is very sensitive and able to detect and quantify F. psychrophilum in water samples and fish spleens with no amplification of the other 130 non-target bacterial isolates. In the water samples investigated, LOD was 20 rpoC gene copies per reaction and QL 103 cells per reaction. The quantification limit was quite high: possibly random losses happened because of DNA uptake in columns during extraction of low cell concentrations. As DNA extraction from samples containing <1000 cells/μl was probably low, the quantification by qPCR was also not reliable. In a 16S rRNA gene F.

The IPCC AR4 WG3 did not adequately describe the reasons for these wide ranges of mitigation potentials and costs due to space constraints. With regard to the range of carbon prices, Table 11.3 in the IPCC AR4 focuses on carbon prices under 100 US $/tCO2 eq, Compound C research buy which is within the scope of the current trend of the carbon market. For

example, the European Unit of Accounting (EUA) price of the European Union Emissions Trading Scheme (EU-ETS) and the Certified Emission Reduction (CER) price for Clean Development Mechanism (CDM) projects vary around 15–30 €/tCO2 eq and 10–20 €/tCO2 eq, respectively, and the value of penalty charges in the EU-ETS market is at 100 €/tCO2 eq. However, transitions toward a low-carbon society are not an extension of the current trends and much greater GHG reductions than the current rate are required in the mid-term on a global scale (Rogelj et al. 2011; IEA 2010). It is also worth analyzing mitigation potentials at carbon prices higher than 100 US $/tCO2 eq. Therefore, this comparison study focuses on technological mitigation potentials up to the carbon price at 200 US $/tCO2 eq, which is close

to double the price of penalty charges at 100 €/tCO2 eq in the EU-ETS market. Moreover, Tables 11.3 and 11.4 in the IPCC AR4 show mitigation potentials only on a global scale and not on a detailed regional scale. Accordingly, this comparison study focuses on results of MAC curves from 0 to 200 US $/tCO2 eq in a more detailed country or region than the IPCC AR4 WG3, and provides comprehensive analysis to show the wide range of comparison results. Comparison design Small molecule library purchase on mitigation potentials and costs Characteristics of the bottom-up approach This comparison study focuses on the results of mitigation potentials and costs using energy-engineering bottom-up models for multi-regions and multi-sectors. The most characteristic aspect of the bottom-up approach

is that it deals with distinct and detailed technology information such as the costs of technologies, energy efficiency of technologies, the diffusion Montelukast Sodium rate of technologies, at regional and sectoral levels. The bottom-up analysis has two different approaches: an accounting approach that accumulates mitigation options compared to the baseline scenario, and a cost optimization approach that minimizes the total system costs. One of the advantages of the bottom-up approach is that the technological feasibility of GHG emission reductions is identified explicitly by mitigation options. However, in the bottom-up analysis it is difficult to take into account the spillover effects of the introduction of mitigation measures (Edenhofer et al. 2006), such as changes in industrial structure, service demand, technology costs and energy prices. Consequently, it is not possible to analyze its economic impacts (Akashi and Hanaoka 2012; Wagner et al. 2012; Akimoto et al. 2012).

Evidence to answer this question should be expected to be preserved in the Precambrian rock record. For example, as is shown here, stromatolites, ACP-196 mw microbially layered deposits dominated today by filamentous and coccoidal cyanobacteria, are present throughout virtually all of the known geological record; cellularly preserved fossils of cyanobacteria dominate the documented record of Precambrian life; and rock-derived

carbon isotopic data are consistent with the presence of photosynthetic microorganisms back to ~3,500 Ma ago and, possibly, to >3,800 Ma ago. Nevertheless, as is also shown here, a firm answer to the question of the time of origin of oxygenic photosynthesis is not yet available: the earliest known stromatolites might have been formed by anoxygenic,

Epigenetics inhibitor rather than O2-producing, photosynthesizers; the cyanobacterium-like fossils in rocks ~3,500 Ma might be remnants of non-O2-producing microbes; and though a vast amount of carbon isotopic data are consistent with the presence of oxygenic photosynthesis as early as ~3,500 Ma ago, they do not rule out the possibility that the role of primary producer in the world’s most ancient ecosystems was played by anaerobic, anoxygenic, photosynthetic bacteria. It should not be surprising that the question of time of origin of O2-producing photosynthesis (i.e., of cyanobacteria) is yet unresolved. In contrast with paleontological studies of the Phanerozoic history of life, the basic outlines of which were already known in the mid-1800s when they served as the basis for Darwin’s

great tome on the Origin of Species, active investigation of the earlier, Precambrian, fossil record did not commence until the mid-1960s, more than a century later (Barghoorn and Schopf 1965; Barghoorn and Tyler 1965; Cloud 1965; Schopf 1968). And although great progress has been made in the ensuing decades (see, for example, Schopf and Bottjer 2009)—showing that Cyclic nucleotide phosphodiesterase Precambrian microbes were abundant, ubiquitous, metabolically diverse, and biotically predominant—knowledge of the early fossil record remains far from complete. Moreover, due to the “geologic cycle,” the repeated sequence of mountain building, erosion, and deposition into sedimentary basins of the eroded mineral grains thus produced, the average “lifetime” of a geological unit is only some 200 Ma. For this reason, the rock record that has survived to the present rapidly decreases with increasing geological age, a petering-out that severely limits the ancient fossil record available for study.

This crude extract was used for both TLC and HPLC. HC-toxin isolated from C. carbonum was used as a standard. For TLC, extracts (10

μl) were spotted onto 250-μm silica plates with adsorbent selleck kinase inhibitor strip (Whatman, GE Healthcare Life Sciences, Piscataway, NJ). Plates were developed in 1:1 acetone/dichloromethane. HC-toxin was detected using an epoxide-specific reagent [45]. For HPLC, 20 μl of extract was combined with 60 μl of acetonitrile and 20 μl of distilled water. The sample was injected onto a C18 reverse phase column (Eclipse XDB-C18 silica, 5 μm, 4.6 × 150 mm; Agilent, Santa Clara, CA) and was eluted with a linear gradient of 10% (v/v) acetonitrile in water to 100% acetonitrile in 30 min at a flow rate of 1 ml/min. The eluant was monitored at 230 nm. HC-toxin eluted from the column between 8 and 9 min. Mass spectrometry was performed at the MSU Mass Spectrometry Facility as described [16]. Nucleic acid methods DNA was extracted from 7-day Sotrastaurin old lyophilized mycelial mats of A. jesenskae grown in potato dextrose broth in still culture

using the Gentra DNA extraction kit (Qiagen, Valencia, CA). Sequencing of genomic DNA was performed by 454 pyrosequencing at the Michigan State University Research Technology Support Facility (MSU RTSF). The total number of base pairs obtained was 483 MB. After assembly by Newbler 2.0, the number of assembled base pairs was 34.4 MB. For DNA blotting, DNA was digested with restriction endonucleases selected specifically to evaluate gene copy number based on the genomic sequence. Internal gene-specific Carnitine palmitoyltransferase II probes were generated based on the assembled genomic sequences. DNA was transferred to Nytran SPC (Whatman, Maidstone, England) and hybridized with 32P-labeled DNA probes. Specific PCR primers were used to close gaps between contigs of individual genes based on their alignment with the genes of TOX2. RNA was extracted as described [46]. RT-PCR followed by 5′ and 3′ RACE was done with the SMART RACE cDNA amplification kit (Clontech, Mountain View, CA). Overlapping gene-specific primers

were designed from the genomic sequence. In most cases, several gene-specific primers were used. PCR products were sequenced directly or cloned into pGem T-easy (Promega), transformed into E. coli DH5α (Invitrogen), and sequenced using M13 forward and reverse primers. Genomic and cDNAcopies of the genes were compared using SPIDEY (NCBI). Bioinformatics BLASTN and TBLASTN searching with the genes of C. carbonum TOX2 against the A. jesenskae genome used stand-alone BLAST version 2.2.15, downloaded from NCBI, and default parameters. Alignments and manual annotation of genes and proteins were done using DNASTAR Lasergene versions 7 or 8 (DNASTAR, Inc., Madison, WI), ClustalW2 (http://​www.​ebi.​ac.​uk/​Tools/​msa/​clustalw2/​), and SPIDEY (NCBI). Assembly of predicted protein sequences was performed using DNASTAR Lasergene software with assistance from FGENESH (http://​www.​softberry.​com) with Alternaria as the training model.

Methods Bacterial strains and DNA preparation A total of 104 B. melitensis strains used in the study were isolated from clinical samples (102 from blood, and 2 from bone marrow). The samples were collected as part of standard patient care between 1957 and 2010 and were fully de-identified. So any ethical approval was not required for the use of these samples. B. melitensis

biovar 1 vaccine strain M5 was also included in this study (Table 2). Bacterial isolates were cultured on Trypticase soy agar containing 5% sheep blood (BD Diagnostic Systems, China Ltd., China) at 37°C for 48 h. All isolates were identified as Brucella species (biovar) on the basis of classical identification procedures: CO2 requirement, H2S production, inhibition of growth by basic fuchsin and thionin, agglutination with monospecific antisera and phage typing [17]. Total genomic DNA was extracted with the DNeasy Blood & Tissue Selleckchem PD173074 Kit (Qiagen China Ltd., China) by following the manufacturer’s protocol for extraction of genomic DNA from Gram-negative Talazoparib manufacturer bacteria. Species-level identification was undertaken by the AMOS-PCR assay [18]. Table 2 The 105 B. melitensis isolates examined in this study Geographical origin Year No. of isolates Panel 1 Genotypes* Inner Mongolia 1955-2006 26 42,63 Qinghai 1965 1 42 Henan 1963,1982

2 42,43 Shanxi 1979-2009 11 42,43,45,63 Shandong 1973,2005 3 42 Shan’xi 1962,2008 5 42 Hebei 2009 1 42 Liaoning 2005 2 42 Guangxi 1961 1 58 Zhejiang 2005,2009 3 42 Fujian 2009 3 42,58 Yunnan 2009 2 58 Beijing 2006 1 42 Guangdong 2006-2010 39 42, 43, 63, CN-1 Hunan 2008 1 42 Jilin 1971 1 42 Tianjin 2010 1 42 Shanghai 2007 1 63 Heilongjiang 1962 1 42 *genotype 42 (1-5-3-13-2-2-3-2), genotype 43 (1-5-3-13-3-2-3-2), genotype 45 (1-5-3-12-2-2-3-2), genotype 58 (1-5-3-13-3-1-3-2) genotype 63 (1-5-3-13-2-3-3-2), genotype CN-1 (1-5-3-13-2-1-3-2)

MLVA-16 genotyping scheme MLVA was performed as previously described [11]. The sixteen primer pairs were divided into three groups as previously described: panel 1 (8 loci including bruce06, bruce08, bruce11, bruce12, Bcl-w bruce42, bruce43, bruce45, and bruce55), panel 2A (3 loci including bruce18, bruce19, and bruce21), and panel 2B (5 loci including bruce04, bruce07, bruce09, bruce16, and bruce30). PCR conditions were as follows: initial denaturation at 94°C for 3 min, and then 30 cycles of 94°C for 30 s, 60°C for 30 s and 72°C for 50 s. Five microliters of the amplification products were loaded in to 2% (panel 1) and 3% (panels 2A and 2B) agarose gels containing ethidium bromide (0.5 μg/ml), visualized under UV light, and photographed. The reference strain B. melitensis 16 M, for which the precise molecular mass is known for each primer pair locus, was used for size comparison.

Assays were performed in triplicate. Statistical

analysis All experiments were performed in triplicate and data MEK phosphorylation were expressed as mean values ± SD. The Pearson product-moment correlation coefficient was used to evaluate the correlation (linear dependence) of cell proliferation, viability and sirolimus concentration. Data were analysed using SPSS 12 statistical software (SPSS Inc. USA) and statistical significance was set at p < 0.05. Results Cell proliferation The results of the MTT assay to detect sirolimus-induced anti-proliferative activity in T24 cell line are found in Table 1. T24 cancer cells were treated with various concentrations of sirolimus. As shown in Figure 1, sirolimus had growth inhibition effects on T24 cancer cells in a dose-dependent manner. Statistically, anti-proliferative activity was correlated with sirolimus concentration, the Pearson correlation of these two markers is r = 0.830 to p < 0.01. Figure 1 Linear relationship between the proliferation

inhibitory rate (%) and sirolimus concentration (y = 0.2074x + 23.299; r 2 = 0.6882). Table 1 Effect of sirolimus in T24 cancer cell line. Concentration A570 nm A690 nm Mean ± SD   0.525 0.201   0 ng/mL 0.828 0.108 0.557 ± 0.207   0.828 0.201     0.588 0.096   5 ng/mL 0.639 0.078 0.481 ± 0.086   0.72 0.33     0.528 0.054   10 ng/mL 0.468 0.063 0.374 ± 0.117   0.47 0.225     0.516 0.213   40 ng/mL 0.489 0.087 0.310 ± 0.087   0.477 0.25     0.78 0.489   60 ng/mL 0.687 0.354 0.267 ± 0.080   0.339 0.162     0.474 0.288   100 ng/mL 0.573 0.246 0.301 ± 0.104   0.657 0.267     0.501 0.276 ICG-001 research buy   150 ng/mL 0.42 0.318 0.22 ± 0.115   0.618 0.285     0.504 0.417   200 ng/mL 0.294 0.255 0.193 ± 0.226   0.576 0.123     0.345 0.264   250 ng/mL 0.3 0.27 0.199 ± 0.249   0.618 0.132   Cell viability The results of cell viability after the incubation of Non-specific serine/threonine protein kinase the T24 cell line with sirolimus at different concentrations are displayed in Figure 2. It can be seen from the figure that there was a concentration-dependent decrease in cell viability

for all concentrations tested. A significant correlation was found between cell viability and sirolimus concentration (r = -0.896, p < 0.01). Figure 2 Linear relationship between the cell viability rate (%) and sirolimus concentration (y = -0.1993x + 85.162; r 2 = 0.8023). Discussion The findings of the present study revealed that sirolimus inhibits T24 bladder cancer cell proliferation and decrease the cell viability including in clinical dose of this mTOR inhibitor. These data may be relevant if we remember the action of the mTOR pathway. mTOR is a 290 kDa serine-threonine kinase that regulates both cell growth and cell cycle progression through its ability to integrate signals from nutrient and growth factor stimuli [24]. Tumour angiogenesis may depend on mTOR signalling.

When the annealing temperature is above 800°C, diffraction peaks of (111), (222), and (333) from the cubic phase of the ZnAl2O4 spinel structure appear in the XRD patterns. This result shows selleck chemical that the multiple crystalline ZnAl2O4 film is synthesized by the high temperature annealing process above 800°C. The surface morphologies of the samples annealed at different temperatures of 700, 800, 1,000, and 1,100°C were observed by SEM, as shown in Figure  12a,b,c,d. The film annealed at relatively low temperature

of 700°C for 0.5 h had a smooth surface morphology as shown in Figure  12a. At annealing temperature of 800°C, the film starts to crystallize, with significant grain boundaries emerge on the surface, as shown in Figure  12b. The crystalline grains in the film grow up with increasing annealing temperature from 1,000 to 1,100°C, as shown in Figure  12c,d. Figure 11 XRD spectra of the ZnO/Al 2 O 3 composite BMS202 films after annealed at different temperatures. Figure 12 SEM images of the ZnO/Al 2 O 3 composite films with optimized ZnO/Al 2 O 3 monocycle ratio of 1:1. Samples were annealed at 700°C (a), 800°C (b), 1,000°C (c), and

1,100°C (d), respectively. Conclusions AZO and ZnAl2O4 films were prepared by alternating atomic layer deposition (ALD) of ZnO/Al2O3 laminates using DEZn, TMA and water. A deposition temperature of 150°C was selected for the ZnO/Al2O3 composite films. The growth per cycle, structure, electrical, and optical properties of the ZnO/Al2O3 laminates were studied at different Al concentration, which was controlled by varying the cycle ratio of ZnO/Al2O3 from 1:2 to 50:1. It is shown that the growth (-)-p-Bromotetramisole Oxalate rate of the ZnO is reduced during the ALD of ZnO/Al2O3 multilayers

due to the etching of the ZnO surface layer during exposure to TMA precursor in Al2O3 cycle. Conductive transparent AZO films were obtained at low Al doping concentration with the minimum resistivity of 2.38 × 10−3 Ω·cm and transmittance above 80% in the visible range. The PL spectroscopy in conjunction with XRD reveals that pure ZnAl2O4 film was synthesized from the composite with alternative monocycle of ZnO and Al2O3 deposited by precise ALD technology. SEM and XRD studies indicate that the crystalline ZnAl2O4 films can be synthesized at annealing temperature from 800°C to 1,100°C. Acknowledgments One of the authors would like to acknowledge Dr. Jun Qian for assisting in X-ray diffraction analysis. This work was supported by Chinese ‘973’ project (no. 2013CB632102) and National Natural Science Foundation of China NSFC (nos. 61275056 and 60977036). References 1. Nomura K, Ohta H, Takagi A, Kamiya T, Hirano M, Hosono H: Room-temperature fabrication of transparent flexible thin-film transistors using amorphous oxide semiconductors. Nature 2004, 432:488–492.CrossRef 2.

In

addition to serving as an educational tool, the series provides a mechanism for physicians to network and collaborate on future endeavors. All of this leads will lead to a more robust, educated workforce. Many telehealth programs have been developing across the world. Some of them however, find difficulties in sustaining their activities once program funding ends. Adding an educational component to a telehealth program may ensure its sustainability in the long-run. The synergy created by different institutions participating in teleconferences for example, can lead to other collaborations in the future. In addition, as physicians become more accustomed to being on video, they can then be better prepared to communicate with patients in the same way. Conclusion The development and advancement of telemedicine over the past years have opened doors to an immense number of possibilities. Not only has https://www.selleckchem.com/products/otx015.html telemedicine been used for consultation, diagnosis and treatment purposes; it is also being used in distance and continuing medical education. Institutions are developing a variety of web-based distance learning programs

as well as formal grand rounds and lectures using telemedicine technology. In particular, telemedicine can be used to overcome disparities in training and education and to deliver higher-quality health care to patients in remote locations. Telemedicine will not only extend the reach of the trauma education but it will also help bridge the gap between limited resources, lack of available staff and reduced budget across many specialties in medicine. Acknowledgements Apoptosis Compound Library This article has been published as part of World Journal of Emergency Surgery Volume 7 Supplement 1, 2012: Proceedings of the World Trauma Congress 2012. The full contents of the supplement are available online at http://​www.​wjes.​org/​supplements/​7/​S1. References

1. Field MJ: Telemedicine: A Guide to Assessing Telecommunications for Health Care In Institute of Medicine. Committee on Evaluating Clinical Applications of Telemedicine. Washington, D.C.:National Academy Press; 1996. 2. American Telemedicine Association: Telemedicine Defined. [http://​www.​americantelemed.​org/​i4a/​pages/​index.​cfm?​pageid=​3333] Accessed April 2012 3. Thomas EJ, Lucke JF, Wuest L, Weavind L, Patel B: Association of telemedicine for remote monitoring of intensive Obeticholic Acid supplier care patients with mortality, complications, and length of stay. JAMA 2009,302(24):2671–8.PubMedCrossRef 4. Simmons S, Alverson D, Poropatich R, D’Iorio J, DeVany M, Doarn C: Applying telehealth in natural and anthropogenic disasters. Telemed J E Health 2008,14(9):968–71.PubMedCrossRef 5. Napolitano LM, Fulda GJ, Davis KA, et al.: Challenging issues in surgical critical care, trauma, and acute care surgery: A report from the critical care committee of the American association for the surgery of trauma. J Trauma 2010,69(6):1619–33.PubMedCrossRef 6.

However, no induction of the adhE (lsa0379) gene encoding an iron-containing aldehyde dehydrogenase

suggested to further reduce lactaldehyde to L-lactate [7] was seen. By CGH [32]lsa1158 and adhE were present in all the L. sakei strains investigated, whereas mgsA was lacking in some strains, indicating that the MgsA function is not vital. Pyruvate metabolism Pyruvate is important in both glycolysis and PKP. It can be converted into lactate by the NAD-dependent L-lactate dehydrogenase, which regenerates NAD+ and maintains the redox balance. This enzyme is encoded by the ldhL selleck kinase inhibitor gene which was down-regulated (0.7-1.4) in all three strains, in accordance with previous findings [50], and the down-regulation was strongest for the LS 25 strain. At the protein level, only LS 25 showed a lower expression of this enzyme during growth on ribose [19]. Genes responsible for alternative fates of pyruvate

(Figure 2) were highly induced in all the strains, however with some interesting strain variation (Table 1). The shift in pyruvate metabolism can benefit the bacteria by generating ATP, or by gaining NAD+ for maintaining the redox Luminespib mouse balance and may lead to various end products in addition to lactate [51]. In all the strains, a strongly up-regulated (2.1-3.0) pox1 gene was observed, and in 23K an up-regulated pox2 (0.7), encoding pyruvate oxidases which under aerobic conditions convert pyruvate to acetyl-phosphate with hydrogen peroxide (H2O2) and CO2 as side products. Accumulation of peroxide ultimately leads to aerobic growth arrest [52]. H2O2 belongs to a group of compounds known as reactive oxygen species and reacts readily with metal ions to yield hydroxyl radicals that damage DNA, proteins and membranes [53]. Remarkable differences in redox activities exist among Lactobacillus species and L. sakei is among those extensively

well equipped to cope with changing oxygen conditions, as well as dealing effectively with toxic oxygen byproducts [7]. 23K up-regulated npr (1.0) encoding NADH peroxidase which decomposes low concentrations of H2O2 to H2O and O2, DOCK10 and all the strains up-regulated the sodA gene (1.7-3.4) encoding a superoxide dismutase which produces hydrogen peroxide from superoxide (O2 -). Various oxidoreductases showed an up-regulation in all the strains (Table 1), indicating the need for the bacterium to maintain its redox balance. The pdhABCD gene cluster encoding components of the pyruvate dehydrogenase enzyme complex (PDC) which transforms pyruvate into acetyl-CoA and CO2 were among the strongly up-regulated (2.1-3.7) genes. The eutD gene encoding a phosphate acetyltransferase which further forms acetyl-phosphate from acetyl-CoA was also induced (1.0-2.0). Pyruvate can be transformed to acetolactate by acetolactate synthase and further to acetoin by acetolactate decarboxylase, before 2,3-butanediol may be formed by an acetoin recuctase (Figure 2).