We used BU.MPT cells, a mouse kidney epithelial cell line, as our primary model, but we also evaluated several epithelial cell lines of distinct tissue origins. Like m phi, mouse kidney epithelial cells recognized apoptotic and necrotic targets through distinct non-competing receptors, Evofosfamide in vivo albeit with lower binding capacity and markedly reduced phagocytosis. Also, modulation of inflammatory activity and

MAPK-dependent signaling by apoptotic and necrotic targets was indistinguishable in kidney epithelial cells and m phi. In contrast, modulation of Akt-dependent signaling differed dramatically between kidney epithelial cells and m phi. In kidney epithelial cells, modulation of Akt was linked to target cell recognition, independently of phagocytosis, whereas in m phi, modulation was linked to phagocytosis. Moreover, recognition of apoptotic and necrotic targets by kidney epithelial cells elicited opposite responses; apoptotic targets inhibited whereas necrotic targets stimulated Akt activity. These data confirm that nonprofessional phagocytes recognize and respond to dying cells, albeit in a manner partially distinct from m phi. By acting as sentinels of environmental

change, apoptotic and necrotic targets may permit neighboring viable cells, especially non-migratory epithelial cells, to monitor and adapt to local stresses.”
“Rotary catalysis in F1F0 ATP synthase is powered by proton translocation through the membrane-embedded F-0 sector. 17DMAG solubility dmso Proton binding and release occur in the middle of the membrane at Asp-61 on transmembrane helix (TMH) 2 of subunit c. Previously the reactivity of Cys substituted into TMH2 revealed extensive aqueous access at the cytoplasmic side as probed with Ag+ and other thiolate-directed reagents. The analysis of aqueous accessibility selleck compound of membrane-embedded regions in subunit c was extended here to TMH1 and the periplasmic side of TMH2. The Ag+ sensitivity of Cys substitutions was more limited on the periplasmic versus cytoplasmic side of TMH2. In TMH1, Ag+ sensitivity was

restricted to a pocket of four residues lying directly behind Asp-61. Aqueous accessibility was also probed using Cd2+, a membrane-impermeant soft metal ion with properties similar to Ag+. Cd2+ inhibition was restricted to the I28C substitution in TMH1 and residues surrounding Asp-61 in TMH2. The overall pattern of inhibition, by all of the reagents tested, indicates highest accessibility on the cytoplasmic side of TMH2 and in a pocket of residues around Asp-61, including proximal residues in TMH1. Additionally subunit a was shown to mediate access to this region by the membrane-impermeant probe 2-(trimethylammonium) ethyl methanethiosulfonate. Based upon these results and other information, a pocket of aqueous accessible residues, bordered by the peripheral surface of TMH4 of subunit a, is proposed to extend from the cytoplasmic side of cTMH2 to Asp-61 in the center of the membrane.

Here, we present two cases undergoing retrograde stenting through the posterior cerebral artery in coil embolization of the PcomA aneurysms.\n\nTo perform retrograde stenting, a microcatheter used for stent delivery was advanced from the vertebral artery (VA) to the terminal internal carotid artery (ICA) via the ipsilateral P1 and the PcomA. The aneurysm sac was selected with another microcatheter for coil delivery through the ipsilateral

ICA. Coil embolization was performed under the protection of a stent placed from the terminal ICA to the PcomA.\n\nDeployment of the stent was successful in both aneurysms treated using selleck chemicals retrograde stenting by the VA approach. Coil deployment was performed through the jailed microcatheter at first. The microcatheter was repositioned through the stent struts later in one case and another microcatheter was inserted into the sac through the stent struts in the other case. Both aneurysms were occluded properly with the coils without procedure-related complications.\n\nBy providing complete neck coverage, retrograde stenting for coil embolization in wide-necked PcomA aneurysms seems to be a good alternative treatment strategy, when the aneurysms are incorporating extended parts of the PcomA, and the PcomA and P1 are big enough to allow passage of the microcatheter for delivery of the stent. However, this technique should be reserved for

those cases with the specific vascular anatomy.”
“Although autologous nerve graft is still the first choice strategy in nerve reconstruction, it has the AP24534 concentration severe disadvantage Geneticin of the sacrifice of a functional nerve. Cell transplantation in a bioartificial conduit is an alternative strategy to improve nerve regeneration. Nerve fibrin conduits were seeded with various cell types: primary Schwann cells (SC), SC-like differentiated bone marrow-derived mesenchymal stem cells (dMSC), SC-like differentiated adipose-derived stem cells (dASC). Two further control groups were fibrin conduits without cells and autografts. Conduits were used to bridge a 1 cm rat sciatic nerve gap in

a long term experiment (16 weeks). Functional and morphological properties of regenerated nerves were investigated. A reduction in muscle atrophy was observed in the autograft and in all cell-seeded groups, when compared with the empty fibrin conduits. SC showed significant improvement in axon myelination and average fiber diameter of the regenerated nerves. dASC were the most effective cell population in terms of improvement of axonal and fiber diameter, evoked potentials at the level of the gastrocnemius muscle and regeneration of motoneurons, similar to the autografts. Given these results and other advantages of adipose derived stem cells such as ease of harvest and relative abundance, dASC could be a clinically translatable route towards new methods to enhance peripheral nerve repair. (C) 2011 IBRO.

Following pre-fractionation of trypsinized proteins by strong cation exchange (SCX) chromatography, pS-MIP enrichment led to the identification of 924 phosphopeptides in the HEK 293T whole-cell lysate, exceeding the PND-1186 inhibitor number identified by TiO2-based enrichment (230). Moreover, the phosphopeptides were extracted with low sequence bias and showed no evidence for the characteristic preference of TiO2 for acidic amino acids (aspartic and glutamic acid). Applying the method to human CSF

led to the discovery of 47 phosphopeptides belonging to 24 proteins and revealed three previously unknown phosphorylation sites.”
“Blarinomys breviceps possesses cryptic and burrowing habits with poorly documented genetics and life history traits. Due to its rarity, only a few specimens and DNA sequences have been deposited in collections worldwide. Here, we present the most comprehensive cytogenetic and molecular characterization of this rare genus. Phylogenetic analyses based on partial cytochrome b sequences were performed, attempting to establish the relationships among individuals

with distinct karyotypes along the geographic distribution of the genus in the Atlantic Forest. Classical and molecular cytogenetics, using banding patterns and FISH of telomeric and whole chromosome X-specific painting probes (obtained from the Akodontini Akodon cursor) were used Acalabrutinib cell line to characterize and compare the chromosomal complements. Molecular phylogenetic analyses recovered 2 main geographically structured clades, northeastern and southeastern with pair-wise sequence divergences among specimens varying between 4.9 and 8.4%. Eight distinct karyomorphs are described: (A) 2n = 52 (50A, XX), (B) 2n = 52 (48A, XY+2Bs), (C) 2n = 45 (42A, XY+1B), (D) 2n = 43 (37A, XX+4Bs), (E) 2n = 37 (34A, XY+1B), (F) 2n = 34 (32A, XX), (G) 2n = 31 (27A, XX+2Bs), (H) 2n = 28 (26A, XY), all with the same number of autosomal arms (FNA = 50). Variation of 0-4 supernumerary chromosomes (Bs) presenting heterogeneity in morphology and distribution of interstitial telomeric sequences (ITSs) is reported. ITSs

are also found in some metacentric autosomes. The phylogeographic separation Caspase inhibitor between 2 major lineages with high levels of genetic divergence, and the wide karyotypic diversity indicate that B. breviceps is a diverse group that warrants taxonomic re-evaluation. Copyright (C) 2012 S. Karger AG, Basel”
“Objective: One basic consequence of cerebral ischemia is energy depletion, manifested by falling levels of adenosine triphosphate (ATP) and a concomitant rise of adenosine monophosphate (AMP). Energy sensor AMP activated protein kinase (AMPK) can be activated in situations of energy stress to maintain ATP reserves. Here, we investigated the mechanism underlying AMPK pathway following cerebral ischemia in rat hippocampus.

4 mm). We evaluated the findings with thin-section CT for each peripheral tumor; emphasis was laid on the predominant internal characteristics (whether the mass is solid), tumor-lung interface characteristics (whether the mass is well-defined with a smooth surface or with lobulation

or spiculation), and surrounding structures (the presence or absence of perivascular thickening adjacent to the tumor). In all patients, most portions of the tumor consisted of a non-calcified solid mass. Contrast enhancement in Selleck GSK923295 varying degrees was observed in the tumors of all 8 patients, who were evaluated with enhanced CT. The tumor-lung interface characteristics observed on the CT images included a well-defined mass with a smooth surface (n = 5), a well-defined mass with lobulation (n = 3), and a mass with spiculation (n = 4). An irregular perivascular thickening adjacent to the tumor was observed in 4 patients. We conclude that peripheral SCLC without associated lymphadenopathy manifests as a non-calcified solid mass and is occasionally characterized by BKM120 solubility dmso perivascular thickening.”
“The incidence of esophageal cancer

has grown over the recent decades and 30 % of esophageal cancer patients are now 75 years or older at the time of diagnosis. The aim of this study was to evaluate trends in management and survival of patients aged 75 years or older with esophageal cancer.\n\nIn the Netherlands cancer registry, we identified all patients aged 75 years or older who were diagnosed

with esophageal cancer between 1989 and 2008. Trends in management and survival were analyzed by time period (1989-2001 vs. 2002-2008), TNM stage, and age (75-79, 80-84, and 85+ years). chi(2) testing was used to analyze time trends in treatment, Kaplan-Meier analysis and log-rank testing to estimate survival, and Cox regression model to calculate hazard ratios for death.\n\nSome 7,253 patients were included in the study. The surgical resection rate increased over the 1989-2008 period from 8.9 to 12.6 % (p = 0.028), especially among patients aged 75-79 years Rapamycin PI3K/Akt/mTOR inhibitor (44.6 vs. 55.4 %, p < 0.001) and patients with TNM stage I disease (12.7 vs. 22.0 %, p < 0.001). The use of definitive chemoradiotherapy (CRT) also increased (0.19 vs. 2.20 %, p < 0.001). Whereas the use of chemotherapy as a single-modality treatment more than doubled (0.64 vs. 1.54 %, p = 0.004), that of radiotherapy alone decreased (38.1 vs. 31.6 %, p < 0.001). Although median survival time was marginally higher in the 2002-2008 period than in 1989-2001, overall 5 year survival rates remained low at 6 and 5 %, respectively (p < 0.001). Five-year survival rate after surgery increased from 16 to 30 % (p < 0.001).\n\nIn patients of 75 years or older, surgical treatment and use of definitive CRT have increased between 1989 and 2008. Also, an increase in the use of chemotherapy as a single modality was noted.

Results: Oral pretreatment with 100, 200, and 400 mg/kg/day of HEAC produced significant (p smaller than 0.001, p smaller than 0.05 Vorinostat cost and p smaller than 0.01) reductions in the paw edema diameter in a non-dose dependent fashion in ACF-induced arthritic rats with the 100 mg/kg/day of HEAC producing the most significant anti-arthritic effect. Similarly, HEAC increased hepatic GSH levels, CAT and SOD activities suggesting possible antioxidant mechanism for its anti-arthritic effect. Conclusion: Overall, results of this

study lend credence to the folkloric use of water decoction of Alchornea cordifolia leaves against rheumatoid arthritis. However, further pharmacological investigations

would be required at isolating and determining the active anti-arthritic molecule(s) in HEAC in the nearest future.”
“AimTo establish how clinicians in New Zealand (NZ) approach screening for and management of coeliac disease (CD) in type 1 diabetes mellitus (T1DM) in their paediatric patients. MethodsAll clinicians caring for children under 15years with T1DM in NZ in 2010 were asked to complete an online survey detailing their personal and departmental approach to diagnosing and managing patients with CD and T1DM. ResultsThirty-four from 37 clinicians responded to the survey. Most clinicians in NZ have a protocol for screening for CD in T1DM, and 25/34 respondents Crenigacestat nmr will screen for CD at diagnosis of T1DM. Those who do not screen will use

symptoms, growth and hypoglycaemia as indicators to test. selleck chemical All use anti-tissue transglutaminase to screen for CD, and 32/34 use biopsy-proven CD as a criterion for commencing gluten-free diet (GFD). Nearly all consultants will still advise a GFD in symptom-free CD and will try to encourage the patients to adopt a GFD if they initially decline. ConclusionsMost clinicians in NZ screen for CD, but there is a wide variation in practice.”
“Serum penicillin G falls to low levels 2 weeks after injection as benzathine penicillin G (BPG) in young adults. Using Pmetrics and previously reported penicillin G pharmacokinetic data after 1.2 million units were given as BPG to 329 male military recruits, here we develop the first reported population pharmacokinetic model of penicillin G after BPG injection. We simulated time-concentration profiles over a broad range of pediatric and adult weights after alternative doses and dose frequencies to predict the probability of maintaining serum penicillin G concentrations of bigger than 0.02 mg/liter, a proposed protective threshold against group A Streptococcus pyogenes ( GAS).

Although radiographic evidence of sacroiliitis is included in the definition, it is not mandatory for the diagnosis of juvenile AS. The aim of this study is to describe pelvic enthesitis-osteitis MRI findings accompanying sacroiliitis in a group of juvenile AS. Eleven patients suffering from low back pain underwent MRI of the pelvis and were enrolled in this retrospective study. The PHA-739358 datasheet mean duration of symptoms was 12 months. The mean age of the 11 cases in our study was 12.18 years (range, 6-19). There were eight boys and

three girls. Anteroposterior radiographs of the pelvis were obtained in all patients. Sacroiliac joint involvement was detected in all of the cases by pelvic MRI. Pathologic signal changes were detected in the pubic symphisis (osteitis pubis) in ten cases, trochanteric bursitis in six cases, coxofemoral joint in five cases, crista iliaca in three cases, and ischion pubis in three cases. There was increased T2 check details signal intensity in eight of the 11 cases (72.7%) relevant with soft tissue edema/inflammation. This high correlation between sacroiliitis and enthesitis suggests that enthesitis

could be an important finding in juvenile AS.”
“Objective: Interaction of advanced glycation end products (AGEs) with their receptors (RAGE) plays an important role in inflammation in auto-immune diseases. Several functional polymorphisms of RAGE have been described. In this study we analysed the role of RAGE polymorphisms in disease susceptibility for systemic lupus erythematosus (SLE). In addition, we investigated whether these polymorphisms in SLE are associated with serum levels of soluble RAGE (sRAGE), renal involvement (lupus nephritis (LN)) and its outcome. Methods: For this cross-sectional study DNA samples

of 97 SLE patients, 114 LN patients and 429 healthy controls (HC) were genotyped for four GPCR Compound Library order RAGE polymorphisms: -429 T/C, -374 T/A, 2184 A/G and Gly82Ser. Differences in genotype frequencies and allele frequencies were tested between patients and HCs. In SLE patients, sRAGE was measured by enzyme-linked immunosorbent assay (ELISA). In addition, association of genotypes with sRAGE and disease severity in LN was analysed. Results: The C allele of -429 T/C, the T allele of -374 T/A and the G allele of 2184 A/G were significantly more prevalent in SLE and LN compared with HC. In LN, the C allele of RAGE -429 T/C, the A allele of -374 T/A and the G allele of RAGE 2184 A/G polymorphism were significantly associated with more proteinuria and worse renal function during the first two years of treatment. No association of genotype with sRAGE was found. Conclusion: RAGE polymorphisms are associated with susceptibility to SLE and LN. In addition, some of these polymorphisms are likely to be associated with disease severity and initial response to treatment in LN. Lupus (2012) 21, 959-968.

“
“Objective: Dose-dependent side effects related

to myo-inositol (MI) oral administration represent a significant shortcoming for its clinical use. Aiming to search for a pharmaceutical form able to be better absorbed, the pharmacokinetic (PK) profile of the new manufactured MI soft gelatin capsule form was evaluated and compared with the commercially available MI powder.\n\nResearch design and methods: A single-dose relative trial, consisting of four phases, was performed LY3039478 on 20 healthy volunteers who received different doses of MI powder and MI soft gelatin capsules. PK profiles related to the two pharmaceutical forms were obtained by analysis of MI plasma concentration, and the respective MI bioavailability

was compared.\n\nResults: The administration of MI powder and MI soft gelatin capsules resulted in a different bioavailability. MI soft gelatin capsule form showed similar PK parameters compared with three times higher doses of MI in powder form.\n\nConclusions: MI soft gelatin capsules displayed an improved bioavailability, allowing to substantially reduce the administered dose and to minimize the dose-dependent side effects. Considering the number of conditions in which MI supplementation is recommended, this evidence could support a broader use of MI in clinical practice.”
“Microtubules (MTs) are essential for many processes in plant cells. MT-associated proteins (MAPS) influence MT polymerization dynamics and enable them to perform their Selleck BI2536 functions. The molecular chaperone Hsp90 has been shown to associate with MTs in animal and plant cells. However, the role of Hsp90-MT binding in plants has not yet been investigated. Here, we show that Hsp90 associates with cortical MTs in tobacco cells and decorates MTs in the phragmoplast. Further, we show that tobacco H5p90_MT binds directly to polymerized MTs in vitro. The inhibition of Hsp90 by geldanamycin (GDA) severely impairs MT re-assembly after cold-induced de-polymerization. Our results indicate that the Selisistat plant Hsp90

interaction with MTs plays a key role in cellular events, where MT re-organization is needed. (c) 2012 Elsevier GmbH. All rights reserved.”
“Vitamin A deficiency causes a marked reduction in the number of T and B cells in the small intestinal tissues. The vitamin A metabolite retinoic acid imprints lymphocytes with gut-homing specificity upon antigenic stimulation. In the small intestinal lamina propria, Peyer’s patches, and mesenteric lymph nodes, there are dendritic cells capable of producing retinoic acid. Their capacity depends on the expression of retinal dehydrogenases (RALDH). RALDH2, encoded by Aldh 1a2, is a major isoform of RALDH in the intestinal dendritic cells under specific pathogen-free conditions, and can be induced by multiple factors constitutively present or induced in the small intestinal microenvironment.

sinensis but no product from the other fungi tested. The detection limit of the primers was demonstrated to be 10ng of pure O. sinensis DNA for conventional PCR and 10pg for nested PCR in a 25 mu l reaction system. Soil samples collected LDK378 manufacturer from the habitat of O. sinensis were also tested using this PCR assay. The results showed that the primer pair and PCR-based assays developed in this study can be applied to the rapid detection of O. sinensis in its natural habitat.”
“Aims: The type 2 muscarinic receptor (M2R) differs from the other G-protein-coupled muscarinic receptor (type 4, or M4R) in tissue distribution and physiologic effects. We studied

the impact of these receptors on sleep and arousal by using M2R and M4R knock-out (KO) mice.\n\nMain Bak apoptosis methods: M2R and M4R KO and genetically intact mice were compared in terms of normal patterns of sleep, responses to sleep loss, infectious challenge and acoustic startle. and acoustic prepulse inhibition

of startle (PPI).\n\nKey findings: Under basal conditions, M2R and M4R KO mice do not differ from the background strain or each other in the amount or diurnal pattern of sleep, locomotor activity, and body temperature. After enforced sleep loss, M2R KO mice, in contrast to the other two strains, show no rebound in slow-wave sleep (SWS) time, although their SWS is consolidated, and they show a greater rebound in time spent in REMS (rapid-eye-movement sleep) and REMS consolidation. During influenza infection, M2R KO mice, as compared with the other strains, show marked hypothermia and a less robust increase in SWS. During Candida albicans infection, M2R KO mice show a greater increase in SWS and a greater inflammatory response than do the other Strains. M2R KO mice also show greater acoustic startle amplitude than does the background strain, although PPI was not different across the 3 strains over a range of stimulus intensities.\n\nSignificance: Taken together, these findings support

different roles for M2R and M4R in the modulation of sleep and arousal during homeostatic challenge. (C) 2009 Elsevier Inc. All rights reserved.”
“There is a need for reliable and sensitive SB273005 biomarkers for renal impairments to detect early signs of kidney toxicity and to monitor progression of disease. Here, antibody suspension bead arrays were applied to profile plasma samples from patients with four types of kidney disorders: glomerulonephritis, diabetic nephropathy, obstructive uropathy, and analgesic abuse. In total, 200 clinical renal-associated cases and control plasma samples from different cohorts were profiled. Parallel plasma protein profiles were obtained using biotinylated and nonfractionated samples and a selected set of 94 proteins targeted by 129 antigen-purified polyclonal antibodies.

Thus, only the subset of individuals who are exposed should be used to make comparisons to estimate the effect of interventions. In this article, we present Bayesian approaches using non-standard mixture distributions to account for true zeros. The performance of the proposed Bayesian methods is compared with the maximum likelihood methods presented in Chu et al. (Stat. Med. 2005; 24:2053-2067) through simulation studies and a randomized chemoprevention trial conducted in Qidong, People’s Republic of China. Copyright DZNeP (C) 2007 John Wiley & Sons, Ltd.”
“Discerning the relative roles of adaptive and nonadaptive processes in generating differences

among populations and species, as well as how these processes interact, is a fundamental aim in biology. Both genetic and phenotypic

divergence across populations can be the product of limited dispersal and gradual genetic drift across populations Linsitinib (isolation by distance), of colonization history and founder effects (isolation by colonization) or of adaptation to different environments preventing migration between populations (isolation by adaptation). Here, we attempt to differentiate between these processes using island populations of Berthelot’s pipit (Anthus berthelotii), a passerine bird endemic to three Atlantic archipelagos. Using microsatellite markers and approximate Bayesian computation, we reveal that the northward colonization of this species ca. 8500years ago resulted in genetic bottlenecks in the colonized archipelagos. We then show that high levels of genetic structure exist across archipelagos and Dinaciclib supplier that these are consistent with a pattern of isolation by colonization, but not with isolation by distance or adaptation. Finally, we show that substantial morphological divergence

also exists and that this is strongly concordant with patterns of genetic structure and bottleneck history, but not with environmental differences or geographic distance. Overall, our data suggest that founder effects are responsible for both genetic and phenotypic changes across archipelagos. Our findings provide a rare example of how founder effects can persist over evolutionary timescales and suggest that they may play an important role in the early stages of speciation.”
“P>Variations in serum prostate-specific antigen (PSA) have been ascribed to A/G nucleotide polymorphisms located at -158 bp (rs266882) and -4643 bp (rs925013), relative to the transcription start site within the promoter of the PSA gene. PSA is also an androgen receptor target (AR) gene and polymorphisms in AR gene are known to affect AR function. Our objective was to compare the impact of these A/G polymorphisms separately or in combination with AR CAG micro satellite on regulation of PSA secretion into seminal plasma and blood in young men.

The clinical this website diagnosis and classification of diabetes have inherent uncertainties that compromise the definition of its onset and the differentiation of its severity stages. A fuzzy system could improve the precision of the diagnosis and classification of diabetic neuropathy because it takes those uncertainties into account and combines different assessment methods. Here, we investigated how plantar pressure abnormalities evolve throughout different severity stages of diabetic polyneuropathy (absent, n = 38; mild, n = 20; moderate,

n = 47; severe, n = 24). Pressure distribution was analysed over five areas while patients walked barefoot. Patients with mild neuropathy displayed an increase in pressure-time integral at the forefoot and a lower peak pressure at the heel. The peak and pressure-time integral under the forefoot and heel were aggravated in later stages of the disease (moderate and severe) compared with early stages of the disease (absent and mild). In the severe group, lower pressures at the

lateral forefoot and hallux were observed, which could be related to symptoms that develop with the aggravation Z-VAD-FMK of neuropathy: atrophy of the intrinsic foot muscles, reduction of distal muscle activity, and joint stiffness. Although there were clear alterations over the forefoot and in a number of plantar areas with higher pressures within each severity stage, they did not follow the aggravation evolution of neuropathy classified by the fuzzy model. Based on these results, therapeutic interventions should begin in Dorsomorphin the early stages of this disease to prevent further consequences

of the disease. (C) 2014 Elsevier B.V. All rights reserved.”
“Aerobic methane-oxidizing bacteria (MOB) use a restricted substrate range, yet 430 species-equivalent operational taxonomical units (OTUs) are found in one paddy soil. How these OTUs physically share their microhabitat is unknown. Here we highly resolved the vertical distribution of MOB and their activity. Using microcosms and cryosectioning, we sub-sampled the top 3-mm of a water-saturated soil at near in situ conditions in 100-mu m steps. We assessed the community structure and activity using the particulate methane monooxygenase gene pmoA as a functional and phylogenetic marker by terminal restriction fragment length polymorphism (t-RFLP), a pmoA-specific diagnostic microarray, and cloning and sequencing. pmoA genes and transcripts were quantified using competitive reverse transcriptase PCR combined with t-RFLP. Only a subset of the methanotroph community was active. Oxygen microprofiles showed that 89% of total respiration was confined to a 0.67-mm-thick zone immediately above the oxic-anoxic interface, most probably driven by methane oxidation.