Acid Pattern Research Articles

The Condition of Acidity, Phosphate, And Nitrate in Indonesian Waters

This research aimed to observe the trend of acidity, nitrate, and phosphate in the Indonesia seas associated with oceanography. Analysis was done by looking at the horizontal condition from main data (acidity, nitrate, and phosphate) and ancillary data (temperature) seasonally in three-layer of depths (0 m, 50 m, and 100 m) for years 2015 using data model of INDESO. The result showed that pattern of acidity, nitrate, and phosphate vary every season. In the upper layer (up to 100 meters), acidity condition ranges from 7.5 to 8, nitrate around 0.01 – 15 mmol N m-3, and phosphate around 0.001 – 1.6 mmol P m-3. The value of acidity is getting lower with depth whereas the nitrate and phosphate values increased with depth. The change in acidity, nitrates and phosphate every season indicates that the monsoon also influences the spread of pH, nitrate and phosphate.Keywords: ocean currents, Indonesia throughflow, sea surface temperature, climate changehate.Â

Early biochemical observations point to nutritional strategies to manage non-alcoholic fatty liver disease

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease globally. The first stage of NAFLD is steatosis, the accumulation of triacylglycerols within hepatocytes. Inflammation and oxidative stress both contribute to progression to more severe disease. In 2004 Clinical Science published two papers reporting on fatty acids and oxidative stress markers in the livers of patients with NAFLD; both these papers are highly cited. One paper reported an altered pattern of fatty acids within the livers of patients with NAFLD; there was a lower contribution of polyunsaturated fatty acids (PUFAs) including both n - 6 and n - 3 PUFAs and an altered balance between n - 6 and n - 3 PUFAs in favour of the former. Ratios of precursor PUFAs to their long chain more unsaturated derivatives were altered in NAFLD and were interpreted to indicate a reduced activity of the pathway of synthesis of long chain highly unsaturated PUFAs. The authors interpreted their findings to indicate that a low hepatic content of n - 3 PUFAs has a causal role in NAFLD. The second paper reported lower hepatic antioxidant defences and increased markers of oxidative stress in NAFLD, consistent with a role for oxidative stress in the disease. Many studies have now explored the effect of supplemental n - 3 PUFAs or antioxidants, including vitamin E, in patients with NAFLD with some benefits being reported. There remains much interest in n - 3 PUFAs and antioxidants as preventive and therapeutic strategies in NAFLD and therefore it seems likely that citation of the two papers from 2004 will be sustained.

High serum uric acid trajectories are associated with risk of myocardial infarction and all-cause mortality in general Chinese population

BackgroundLong-term patterns of serum uric acid (SUA) and their association with the risk of myocardial infarction (MI) and mortality are poorly characterized as prior studies measured SUA at a single time point. This study aimed to identify SUA trajectories and determine their associations with incident MI and all-cause mortality.MethodsWe included 85,503 participants who were free of MI in or prior 2012 from the Kailuan study. SUA trajectories during 2006–2012 were identified by group-based trajectory modeling. Cox proportional hazard models were used to assess the association of SUA trajectories with MI and all-cause mortality.ResultsWe identified three SUA trajectories during 2006–2012: low-stable (n=44,124, mean SUA: 236–249 μmol/L), moderate-stable (n=34,431, mean SUA: 324–354 μmol/L) and high-stable (n=6,984, mean SUA: 425–463 μmol/L). During a median follow-up of 6.8 years, we documented 817 (0.96%) incident MI and 6498 (7.60%) mortality. Compared with the low-stable group, high-stable group experienced a higher risk of MI (hazard ratio [HR], 1.35; 95% confidence [CI], 1.07–1.71) and all-cause mortality (HR, 1.22; 95% CI, 1.12–1.33). Multiple sensitivity analyses yielded similar results. Additionally, the association of SUA trajectory with MI and all-cause mortality was more pronounced in individuals without a history of hypertension (P-interaction=0.0359) and those aged <60 years (P-interaction<0.0001), respectively.ConclusionsHigher SUA trajectories were associated with altered risk of MI and all-cause mortality, suggesting that monitoring SUA trajectory may assist in identifying subpopulations at higher risk of MI and all-cause mortality.

Functional role of formate dehydrogenase 1 (FDH1) for host and nonhost disease resistance against bacterial pathogens.

Nonhost disease resistance is the most common type of plant defense mechanism against potential pathogens. In the present study, the metabolic enzyme formate dehydrogenase 1 (FDH1) was identified to associate with nonhost disease resistance in Nicotiana benthamiana and Arabidopsis thaliana. In Arabidopsis, AtFDH1 was highly upregulated in response to both host and nonhost bacterial pathogens. The Atfdh1 mutants were compromised in nonhost resistance, basal resistance, and gene-for-gene resistance. The expression patterns of salicylic acid (SA) and jasmonic acid (JA) marker genes after pathogen infections in Atfdh1 mutant indicated that both SA and JA are involved in the FDH1-mediated plant defense response to both host and nonhost bacterial pathogens. Previous studies reported that FDH1 localizes to mitochondria, or both mitochondria and chloroplasts. Our results showed that the AtFDH1 mainly localized to mitochondria, and the expression level of FDH1 was drastically increased upon infection with host or nonhost pathogens. Furthermore, we identified the potential co-localization of mitochondria expressing FDH1 with chloroplasts after the infection with nonhost pathogens in Arabidopsis. This finding suggests the possible role of FDH1 in mitochondria and chloroplasts during defense responses against bacterial pathogens in plants.

Hot isopropanol quenching procedure for automated microtiter plate scale 13C-labeling experiments

BackgroundCurrently, the generation of genetic diversity for microbial cell factories outpaces the screening of strain variants with omics-based phenotyping methods. Especially isotopic labeling experiments, which constitute techniques aimed at elucidating cellular phenotypes and supporting rational strain design by growing microorganisms on substrates enriched with heavy isotopes, suffer from comparably low throughput and the high cost of labeled substrates.ResultsWe present a miniaturized, parallelized, and automated approach to 13C-isotopic labeling experiments by establishing and validating a hot isopropanol quenching method on a robotic platform coupled with a microbioreactor cultivation system. This allows for the first time to conduct automated labeling experiments at a microtiter plate scale in up to 48 parallel batches. A further innovation enabled by the automated quenching method is the analysis of free amino acids instead of proteinogenic ones on said microliter scale. Capitalizing on the latter point and as a proof of concept, we present an isotopically instationary labeling experiment in Corynebacterium glutamicum ATCC 13032, generating dynamic labeling data of free amino acids in the process.ConclusionsOur results show that a robotic liquid handler is sufficiently fast to generate informative isotopically transient labeling data. Furthermore, the amount of biomass obtained from a sub-milliliter cultivation in a microbioreactor is adequate for the detection of labeling patterns of free amino acids. Combining the innovations presented in this study, isotopically stationary and instationary automated labeling experiments can be conducted, thus fulfilling the prerequisites for 13C-metabolic flux analyses in high-throughput.

Patterns of free amino acids in tundra soils reflect mycorrhizal type, shrubification, and warming

The soil nitrogen (N) cycle in cold terrestrial ecosystems is slow and organically bound N is an important source of N for plants in these ecosystems. Many plant species can take up free amino acids from these infertile soils, either directly or indirectly via their mycorrhizal fungi. We hypothesized that plant community changes and local plant community differences will alter the soil free amino acid pool and composition; and that long-term warming could enhance this effect. To test this, we studied the composition of extractable free amino acids at five separate heath, meadow, and bog locations in subarctic and alpine Scandinavia, with long-term (13 to 24 years) warming manipulations. The plant communities all included a mixture of ecto-, ericoid-, and arbuscular mycorrhizal plant species. Vegetation dominated by grasses and forbs with arbuscular and non-mycorrhizal associations showed highest soil free amino acid content, distinguishing them from the sites dominated by shrubs with ecto- and ericoid-mycorrhizal associations. Warming increased shrub and decreased moss cover at two sites, and by using redundancy analysis, we found that altered soil free amino acid composition was related to this plant cover change. From this, we conclude that the mycorrhizal type is important in controlling soil N cycling and that expansion of shrubs with ectomycorrhiza (and to some extent ericoid mycorrhiza) can help retain N within the ecosystems by tightening the N cycle.

Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis

BackgroundBacteria and archaea produce an enormous diversity of modified peptides that are involved in various forms of inter-microbial conflicts or communication. A vast class of such peptides are Ribosomally synthesized, Postranslationally modified Peptides (RiPPs), and a major group of RiPPs are graspetides, so named after ATP-grasp ligases that catalyze the formation of lactam and lactone linkages in these peptides. The diversity of graspetides, the multiple proteins encoded in the respective Biosynthetic Gene Clusters (BGCs) and their evolution have not been studied in full detail. In this work, we attempt a comprehensive analysis of the graspetide-encoding BGCs and report a variety of novel graspetide groups as well as ancillary proteins implicated in graspetide biosynthesis and expression.ResultsWe compiled a comprehensive, manually curated set of graspetides that includes 174 families including 115 new families with distinct patterns of amino acids implicated in macrocyclization and further modification, roughly tripling the known graspetide diversity. We derived signature motifs for the leader regions of graspetide precursors that could be used to facilitate graspetide prediction. Graspetide biosynthetic gene clusters and specific precursors were identified in bacterial divisions not previously known to encode RiPPs, in particular, the parasitic and symbiotic bacteria of the Candidate phyla radiation. We identified Bacteroides-specific biosynthetic gene clusters (BGC) that include remarkable diversity of graspetides encoded in the same loci which predicted to be modified by the same ATP-grasp ligase. We studied in details evolution of recently characterized chryseoviridin BGCs and showed that duplication and horizonal gene exchange both contribute to the diversification of the graspetides during evolution.ConclusionsWe demonstrate previously unsuspected diversity of graspetide sequences, even those associated with closely related ATP-grasp enzymes. Several previously unnoticed families of proteins associated with graspetide biosynthetic gene clusters are identified. The results of this work substantially expand the known diversity of RiPPs and can be harnessed to further advance approaches for their identification.

Mass Spectrometry Imaging Analysis of Metabolic Changes in Green and Red Tomato Fruits Exposed to Drought Stress

Plant metabolism is altered in response to various environmental changes. In vegetable crops such as tomato (Solanum lycopersicum), the metabolic composition of fruits varies depending on the variety or cultivar as well as the cultivation method used. Few studies have examined the metabolic fluctuations in fruits under stress conditions, such as drought. We previously examined the metabolomes of mature green tomato fruits, which undergo drastic changes in chemical composition during ripening, and mature red fruits in response to drought stress. We detected or predicted fluctuations in the levels of fatty acids and phospholipid constituents, such as inositol and ethanolamine. In this study, we determined the localizations of these metabolites in fruits using mass spectrometry imaging. The accumulation patterns of stearic acid and palmitic acid were similar, but unlike these fatty acids, oleic acid accumulated to high levels in the placenta. Inositol is involved in various physiological processes; under drought conditions, this metabolite is synthesized by a different pathway compared to under normal conditions. The biosynthesis of pectin, a component of the gel surrounding the seeds, was suppressed under drought stress but increased in seeds. We propose that under drought conditions, a shift to phospholipid biosynthesis occurs that protects seeds from dehydration.

Spatial prediction of soil acidity and nutrients for site-specific soil management in Bedele district, Southwestern Ethiopia

BackgroundUnderstanding the spatial variability of soil properties is useful to tailor site-specific agricultural inputs to enhance crop production on a sustainable basis. This study was aimed to assess and map the spatial patterns of soil acidity and nutrients using geostatistical methods and support site-specific lime and fertilizer recommendations in Bedele district, Southwestern Ethiopia.MethodsSoil samples were collected from agricultural land at a depth of 20 cm using grid sampling technique. The semivariogram analysis was performed for accurate spatial prediction and the kriging technique was used for interpolation of soil parameters.ResultsSoil pH varied between 4.5 and 6.8. Soil organic carbon (OC) content ranged from 0.3 to 5.6% and the mean soil OC density was 0.81 kg m−2. Available phosphorus (AvP) ranged from 0.8 to 38.6 mg kg−1 and nearly 80.23% of the soils exhibited very low to low AvP that could be due to fixation by strong acidity. Soils of the study area exhibited very high exchangeable potassium (K), but very low exchangeable calcium (Ca) and magnesium (Mg). The potassium to magnesium ratio (K:Mg) ranged from 0.2:1 to 10.9:1, while the values of calcium to magnesium ratio (Ca:Mg) varied between 0.3 and 3.4. Among the soil parameters, exchangeable Ca (CV = 54%) and K:Mg ratio (CV = 57.62%) were more variable than other soil parameters. Spatial variability was lowest for soil pH (CV = 10%).ConclusionsMajor portions of the study site were affected by strong acidity (pH ≤ 5.5). Accordingly, about 89% of the soils require lime that varied between 0.09 and 3.6 tons ha−1. In addition to soil acidity, deficiency of available P, Ca, and Mg were the major liming factors affecting crop production in the study area. Digital soil mapping was used to show the spatial variability of soil acidity and nutrients across agricultural land and applied for efficient lime and nutrients advisory works.

Predicted Functional and Structural Diversity of Receiver Domains in Fungal Two-Component Regulatory Systems

ABSTRACTFungal two-component regulatory systems incorporate receiver domains into hybrid histidine kinases (HHKs) and response regulators. We constructed a nonredundant database of 670 fungal receiver domain sequences from 51 species sampled from nine fungal phyla. A much greater proportion (21%) of predicted fungal response regulators did not belong to known groups than previously appreciated. Receiver domains in Rim15 response regulators from Ascomycota and other phyla are very different from one another, as are the duplicate receiver domains in group XII HHKs. Fungal receiver domains from five known types of response regulators and 20 known types of HHKs exhibit distinct patterns of amino acids at conserved and variable positions known to be structurally and functionally important in bacterial receiver domains. We inferred structure/activity relationships from the patterns and propose multiple experimentally testable hypotheses about the mechanisms of signal transduction mediated by fungal receiver domains.

Mucosal Microbiota and Metabolome in the Ileum of Hu Sheep Offered a Low-Grain, Pelleted or Non-pelleted High-Grain Diet.

Alterations in mucosal microbiota and metabolites are critical to intestinal homeostasis and host health. This study used a combination of 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC/MS) to investigate mucosal microbiota and their metabolic profiles in the ileum of Hu sheep fed different diets. Here, we randomly allocated 15 Hu sheep to three diets, a non-pelleted low-grain diet (control diet; CON), a non-pelleted high-grain diet (HG), and a pelleted high-grain diet (HP). After 60 days of treatment, ileal mucosal samples were collected for microbiome and metabolome analysis. The results of principal coordinate analysis and permutation multivariate analysis showed that there was a tendency for microbial differentiation between the CON and HG groups (P < 0.1), although no significant difference between the HG and HP groups was observed (P > 0.05). Compared with the CON diet, the HG diet decreased (P < 0.05) the abundance of some probiotic species (e.g., Sphingomonas and Candidatus Arthromitus) and increased (P < 0.05) the abundance of acid-producing microbiota (e.g., Succiniclasticum, Nesterenkonia, and Alloprevotella) in the ileal mucosa. Compared with the HG diet, the HP diet decreased (P < 0.05) the abundance of Alloprevotella and increased (P < 0.05) the abundance of Mycoplasma in the ileal mucosa. Furthermore, partial least squares discriminant analysis and orthogonal partial least-squared discriminant analysis indicated that different dietary treatments resulted in different metabolic patterns in the ileal mucosa of the CON, HG, and HP groups. The HG diet altered (VIP > 1 and P < 0.05) the metabolic patterns of amino acids, fatty acids, and nucleotides/nucleosides (such as increased amounts of ornithine, tyrosine, cis-9-palmitoleic acid, and adenosine) compared with the CON diet. However, 10 differential metabolites (VIP > 1 and P < 0.05; including tyrosine, ornithine, and cis-9-palmitoleic acid) identified in the HG group exhibited a diametrically opposite trend in the HP group, suggesting that the HP diet could partially eliminate the changes brought upon by the HG diet. Collectively, our findings demonstrate that different diets altered the ileal mucosal microbiota and metabolites and provide new insight into the effects of high-grain diets on the intestinal health of ruminant animals.

Incidence of potato green aphid and Lyriomiza sp. in radish plants grown on different levels of organic fertilizer

Radish is a short cycle horticultural product from family Brassicaceae. Between the insects found on radish leaves, potato green aphid (Myzus persicae Sulzer) is one of the main pests of this culture, causing economic damage. Synthetic fertilizers used in conventional crops can promote changes in the pattern of amino acids in plants, leading to a higher insect damage. The source of fertilization is one of the factors that could influence in the incidence of pests. The objective of the study was to evaluate the incidence of potato green aphid and other pests on radish plants grown with different doses of organic fertilizer. The experiment was carried under semi-field conditions, in Fortaleza (Ceará State). A completely randomized design was used, with six replicates. The treatments consisted of five doses of organic compost (0; 45; 60; 75; 90 t.ha-1). For the population survey of pests and natural enemies, counts were made in three evaluations (7, 14 and 21 days after sowing). The counting data were subjected to deviance analysis using a generalized linear model (GLM). It was observed significant differences in the number of adults M. persicae in the treatments of 75 and 90 t.ha-1. Presence of leafminer (Lyriomiza sp.) was observed on plants without and with the lower doses of organic fertilizer. Even using organic fertilizers that promote a slower liberation of nutrients, high incidence of pests (Mainly M. persicae) was observed on radish plants.

Strength-Dependent and Strength-Independent Dissolution Patterns of Poorly-Soluble Drugs. Case Example: Valsartan

This study aims to investigate the strength-dependent dissolution pattern of two-dose strengths of valsartan: the low-dose strength of 80 mg and high-dose strength of 320 mg. For this purpose, the dissolution testing was carried out in media of buffer solutions that resemble physiological characteristics of the gastrointestinal fluid (GIF). The influence of various physiological GIF characteristics (pH, buffer capacity β, and ionic strength I) on the dissolution of a weakly acidic biopharmaceutical classification system (BCS) class II drug valsartan present in two-dose strengths was investigated. The strength-dependent and strength-independent dissolution patter was determined based on the similarity/dissimilarity of the dissolution profiles of valsartan 80 and 320 tablets using the f2 similarity test. Valsartan dissolution showed either strength-dependent or strength-independent behavior for various values of pH, buffer capacity β, ionic strength I, and sink condition S of the tested media. Results of this study shed light on the importance of studying physiological characteristics of the GIF for multiple-strength drug products for better predicting the dissolution pattern of weak acids in vivo.

A Natural Antifungal from Cassava Starch Fermentation Wastewater

Sour cassava starch production process, during the fermentation step, an acidic wastewater is generated, in this study named wastewater of cassava starch fermentation (WCSF). It has been studied the effect of WCSFs (from three industrial source: WCSF 1, 2 and 3) and patterns of organic acids (lactic, acetic, propionic and butyric acids, which were the main organic acids present in the WCSFs) singly or together on the development and growing of Botrytis cinerea, Monilinia fructicola and Colletotrichum gloeosporiodes. WCSFs showed antimicrobial effect on the three fungi studied. WCSF2 inhibited the germination of conidia from the three fungi, while WCSFs 1 and 3 inhibited conidia germination of B. cinerea and C. gloeosporiodes. The acetic, propionic, butyric and the mix acids were also effective in the reduction of conidial germination. In the analysis of mycelia growth, it has been observed that the growing was statically smaller, in relation to negative control, for all fungi in the treatments with the WCSFs and with the pattern solution of butyric acid. Which suggest that the WCSFs compounds and butyric acid are effective inhibitor for fungi and justify future studies using this wastewater.

1872-P: Metabolomic Profiling during Diabetic Ketoacidosis (DKA) Demonstrates Unique Defects Underlying the Pathophysiology of Ketosis-Prone Diabetes

Obese patients with ketosis-prone type 2 diabetes (“A-β+ KPD”) have increased catabolism of the ketogenic amino acids leucine/isoleucine (Leu/Ile) and impaired ketone oxidation when stable and normoglycemic (Patel et al, Diabetes 2013). We performed comparative serum metabolomics on patients at presentation with hyperglycemic crisis without (N = 29) or with (N = 73) DKA compared to healthy controls (N = 17). The diabetic groups included normal weight and overweight/obese subgroups. DKA patients had higher plasma cortisol and catecholamines and lower C-peptide than the other groups. Three metabolite patterns distinguished the DKA patients from the other groups: 1) Elevated levels of Leu/Ile and of their respective ketoacids, no difference in isovaleryl carnitine (C5) but markedly lower ratio of C5 to C2 (acetyl carnitine) - implying accelerated shunting of Leu/Ile into their catabolic pathways but impaired oxidation because defective TCA cycle activity restrains acetyl CoA entry and metabolism. These changes were most pronounced in obese DKA patients, recapitulating the pattern of A-β+ KPD patients when stable; 2) Markedly decreased levels of glutamate, ammonia and many non-essential amino acids including citrulline, in the presence of increased glutamine, suggesting a defect in glutaminase activity; 3) Low levels of 3-methyl histidine, suggesting a surprising decrease in muscle protein breakdown. The pattern of amino acids and their metabolites among the DKA (especially obese) patients indicate that both increased ketone production from Leu/Ile and their blunted oxidation contribute to the proclivity to develop DKA; elevated leucine and low citrulline could contribute to beta cell dysfunction via mTOR hyperactivity and diminished intracellular arginine availability. Thus serum metabolomic profiling during an acute DKA episode helps define a unique pathophysiology underlying the phenotype of obese ketosis-prone T2D. Disclosure J.W. Hsu: None. P. Mehta: None. K.R. Keene: None. S.N. Mulukutla: None. E.I. Caducoy: None. W. Peacock: None. A. Balasubramanyam: None. F. Jahoor: None. Funding National Institutes of Health (R01DK101411)

Assessment of gastric acidity by short-duration intragastric pH-monitoring with standardised breakfast in functional and some other dyspepsias

IntroductionPreliminary assessment of gastric secretion in the treatment of organic and functional dyspepsia may offer advantages over the empirical administration of proton pump inhibitors suggested by most clinical guidelines.AimTo develop a simplified pH-metric test with standardised meal, and on its basis to perform an assessment of the functional state of gastric secretion in the most common dyspepsias.Material and methodsSerum pepsinogen 1 and 2 were used for reference. Intragastric pH-monitoring was performed during 45 min in basal phase and 135 min after provocative breakfast (507 kcal, 100 mg caffeine). Consecutive adults enrolled in the study were divided into groups: 1 – “Non-dyspeptic” – 30 persons; 2 – “Duodenal peptic ulcer” – 13; 3 – “GERD” – 82; and 4 – “Functional dyspepsia” – 125 patients.ResultsThere was a moderate association between concentration of pepsinogen-1 and parameters of pH-monitoring. The best correlation coefficients were for the nadir pH in basal conditions and the time of acid neutralisation > 3.5 after the meal – r = –0.534 and r = –0.541, respectively (p < 0.0001). Using these two parameters we considered discriminants for four patterns of acidity. Proposed criteria of Hipo-anacidity included an absence of active secretion of hydrochloric acid in basal (pHmin > 5) and postprandial phases, with the achievement of stable pH < 3.5 after 80 min from meal time. They showed sensitivity 88.9% and specificity 100%. In cases of a detected pattern of hyperacidity, these parameters were 80% and 66.67%, respectively. According to the prevalence of hyperacidic cases, the groups were ranked in the following order: duodenal ulcer (76.9%) – GERD (51.1%) – functional dyspepsia (40.8%) – non-dyspeptic (19.0%).ConclusionsAcid production is increased among patients with functional dyspepsia. There is a small number of patients with functional dyspepsia (12.1%) with hypochlorhydria due to atrophic gastritis. The latter was independently associated with age > 50 years (OR = 20.139), symptoms of postprandial distress-syndrome (OR = 9.821), and signs of atrophy (OR = 5.914) after conventional endoscopy.

Metabolic reprogramming of tumors and its research progress in bladder cancer

Almost all tumors have varying degrees of metabolic changes during the tumorigenesis and development, which are collectively referred to as metabolic reprogramming. Metabolic reprogramming leads to a large difference in the metabolic patterns of glucose, glutamine, fatty acids and other substances in tumor cells, and is also considered to be an important biomarker of cancer. Many studies have confirmed that metabolic reprogramming provides sufficient energy and material basis for the growth of tumor cells, and has a positive impact on the biological behavior of tumor cells. It also has metabolic reprogramming in the occurrence and development of bladder cancer, which plays an important role in maintaining the growth of tumor cells and enhancing the chemoresistance of bladder cancer. Therefore, to explore the correlation between metabolic reprogramming and bladder cancer and its potential mechanisms, to explore specific drug targets and effective interventions, may provide a groundbreaking idea for the prevention and treatment of bladder cancer. Key words: Metabolic reprogramming; Glycolysis; Bladder cancer; Targeted therapy

Comprehensive analysis of multiprotein bridging factor 1 family genes and SlMBF1c negatively regulate the resistance to Botrytis cinerea in tomato

BackgroundMultiprotein bridging factor 1 s (MBF1s) are members of the transcriptional co-activator family that have involved in plant growth, development and stress responses. However, little is known about the Solanum lycopersicum MBF1 (SlMBF1) gene family.ResultsIn total, five SlMBF1 genes were identified based on the tomato reference genome, and these genes were mapped to five chromosomes. All of the SlMBF1 proteins were highly conserved, with a typical MBF1 domain and helix-turn-helix_3 domain. In addition, the promoter regions of the SlMBF1 genes have various stress and hormone responsive cis-regulatory elements. Encouragingly, the SlMBF1 genes were expressed with different expression profiles in different tissues and responded to various stress and hormone treatments. The biological function of SlMBF1c was further identified through its overexpression in tomato, and the transgenic tomato lines showed increased susceptibility to Botrytis cinerea (B. cinerea). Additionally, the expression patterns of salicylic acid (SA)-, jasmonic acid (JA)- and ethylene (ET)- mediated defense related genes were altered in the transgenic plants.ConclusionsOur comprehensive analysis provides valuable information for clarifying the evolutionary relationship of the SlMBF1 members and their expression patterns in different tissues and under different stresses. The overexpression of SlMBF1c decreased the resistance of tomato to B. cinerea through enhancing the gene expression of the SA-mediated signaling pathway and depressing JA/ET-mediated signaling pathways. These results will facilitate future functional studies of the transcriptional co-activator family.

Residual solvent or intrinsically formed during production: analysing volatile compounds in unrefined vegetable oils using headspace gas chromatography coupled with mass spectrometry

ABSTRACTVegetable oils are an essential part of a healthy and balanced diet and have major economic significance. The type of production, whether performed by extraction with solvents, or by mechanical techniques, significantly influences the quality of the oil and its potential field of use. Occasionally, volatile organic substances, which are considered indicative for an oil that has been produced by solvent extraction, are detected in unrefined vegetable oils. This can have a negative impact on high-quality oil mills and their reputation. The goal of the study was to analyse unrefined oils of different raw materials for such compounds. A previously developed and validated method using headspace gas chromatography coupled with a mass spectrometry was used for this task. Another aim was to determine the origin of any solvent residues in the vegetable oils and to find ways to avoid them. Complementary measurements by solid phase micro extraction gas chromatography were conducted to compare the results of the measurements to an orthogonal methodology. Multivariate data analysis was used to find correlations between the spectrum of substances in the oil and other parameters like the producer of the oil or the pattern of fatty acids.

Insights into structural dynamics of allosteric binding sites in HCV RNA-dependent RNA polymerase

Inhibition of the viral RNA-dependent RNA polymerase (RdRp) to resolve chronic infection is a useful therapeutic strategy against Hepatitis C virus (HCV). Non-nucleoside inhibitors (NNIs) of RdRp are small molecules that bind tightly with allosteric sites on the enzyme, thereby inhibiting polymerase activity. A large number of crystal structures (176) were studied to establish the structure–activity relationship along with the mechanism of inhibition and resistance between HCV RdRp and NNIs at different allosteric sites. The structure and the associated dynamics are the blueprint to understand the function of the protein. We have implemented the ligand-based pharmacophore and molecular dynamic simulations to extract the possible local and global characteristics of RdRp upon NNI binding and the structural–dynamical features possessed by the known actives. Our results suggest that the NNI binding induces significant fluctuations at the atomic level which are critical for enzymatic activity, with minimal global structural alterations. Residue-wise mapping of interactions of NNIs at different sites exhibited some conserved interaction patterns of key amino acids and water molecules. Here, the structural insights are explored to understand the correlation between the dynamics of protein’s subdomains and function at the molecular level, useful for genotype-specific rational designing of NNIs.Communicated by Ramaswamy H. Sarma