Biotransformation of aromatic compounds from wastewaters containing N and/or S, by nitrification/denitrification: a review

This review presents progress made over the last decades in the understanding of the metabolic capabilities of nitrifying and denitrifying microorganisms for the biotransformation of nitrogen, sulfur, and carbon compounds present in wastewaters. There are nowadays still many discoveries to be made about the metabolism, phylogeny and ecological behavior of bacteria that play an important role in the nitrogen cycle. The interest of the scientific community in the biological nitrogen cycle is at present very high, because it can be linked to either sulfur or carbon cycles. The connection of biological cycles is of the utmost technological relevance as it has allowed the simultaneous elimination of reduced sulfur and phenolic compounds under nitrifying or denitrifying conditions. The environmental factors affecting the nitrification and denitrification biological processes are described in this review.     

Bistability in fatty-acid oxidation resulting from substrate inhibition

In this study we demonstrated through analytic considerations and numerical studies that the mitochondrial fatty-acid β-oxidation can exhibit bistable-hysteresis behavior. In an experimentally validated computational model we identified a specific region in the parameter space in which two distinct stable and one unstable steady state could be attained with different fluxes. The two stable states were referred to as low-flux (disease) and high-flux (healthy) state. By a modular kinetic approach we traced the origin and causes of the bistability back to the distributive kinetics and the conservation of CoA, in particular in the last rounds of the β-oxidation. We then extended the model to investigate various interventions that may confer health benefits by activating the pathway, including (i) activation of the last enzyme MCKAT via its endogenous regulator p46-SHC protein, (ii) addition of a thioesterase (an acyl-CoA hydrolysing enzyme) as a safety valve, and (iii) concomitant activation of a number of upstream and downstream enzymes by short-chain fatty-acids (SCFA), metabolites that are produced from nutritional fibers in the gut. A high concentration of SCFAs, thioesterase activity, and inhibition of the p46Shc protein led to a disappearance of the bistability, leaving only the high-flux state. A better understanding of the switch behavior of the mitochondrial fatty-acid oxidation process between a low- and a high-flux state may lead to dietary and pharmacological intervention in the treatment or prevention of obesity and or non-alcoholic fatty-liver disease.     

Marker-assisted selection for the wide-spectrum resistance to root-knot nematodes conferred by the Ma gene from Myrobalan plum (Prunus cerasifera) in interspecific Prunus material

Prunus species express a more or less wide spectrum of resistance to root-knot nematodes (RKN) of the genus Meloidogyne. Among them, sources from Myrobalan plum (P. cerasifera) control all major and minor RKN species tested. In this outbreeding species, the clones P.2175 and P.2980 are heterozygous for the Ma single dominant gene and carry the alleles Ma1 and Ma3, respectively. Each allele confers a high-level resistance to the predominant RKN, M. arenaria, M. incognita and M. javanica and to the Florida isolate of an unknown Meloidogyne sp. which overcomes the resistance from peach and almond sources. The polymorphism of two coupling-phase SCAR markers tightly linked to Ma, SCAL19₆₉₀ and SCAFLP2₂₀₂, was evaluated within diverse diploid Prunus accessions. This material belongs to the subgenera Prunophora (Myrobalan and apricot) or Amygdalus (peach, almond and almond-peach) and includes the RKN resistance sources Nemared, Alnem 1 and GF.557. The alleles SCAL19₆₉₀ and SCAFLP2₂₀₂ were not present in three apricot cultivars (Moniqui, Luizet and Stark Early Orange) representative of the genetic diversity of this species and they segregated in an interspecific cross between P.2980 and apricot. These results suggest that apricot, reported as resistant to M. arenaria, M. incognita and M. javanica, and the Myrobalan plum might possess two different resistance systems. SCAL19₆₉₀ and SCAFLP2₂₀₂ were also absent from all tested Amygdalus material, whatever its resistance to RKN. Eight Myrobalan×Amygdalus segregating progenies including bispecific (P.2175 or P.2980×peach or almond) and trispecific (P.2175 or P.2980×almond-peach) hybrids were tested with the Florida isolate to identify individuals carrying the Ma resistance alleles. Both SCARs were then evaluated for segregation in these progenies to develop marker-assisted selection of Prunus interspecific rootstocks. SCAL19₆₉₀ and SCAFLP2₂₀₂ could be clearly detected and their tight linkage to Ma1 and Ma3 was confirmed. Consequently these SCARs appear to be powerful tools to screen for RKN resistance conferred by the Ma gene. They should also facilitate marker-assisted pyramiding of Ma with other resistance genes from the Amygdalus subgenus or from the botanically-related Armeniaca section.     

Polo-like kinase confers MPF autoamplification competence to growing Xenopus oocytes

During oogenesis, the Xenopus oocyte is blocked in prophase of meiosis I. It becomes competent to resume meiosis in response to progesterone at the end of its growing period (stage VI of oogenesis). Stage IV oocytes contain a store of inactive pre-MPF (Tyr15-phosphorylated Cdc2 bound to cyclin B2); the Cdc25 phosphatase that catalyzes Tyr15 dephosphorylation of Cdc2 is also present. However, the positive feedback loop that allows MPF autoamplification is not functional at this stage of oocyte growth. We report that when cyclin B is overexpressed in stage IV oocytes, MPF autoamplification does not occur and the newly formed cyclin B-Cdc2 complexes are inactivated by Tyr15 phosphorylation, indicating that Myt1 kinase remains active and that Cdc25 is prevented to be activated. Plx1 kinase (or polo-like kinase), which is required for Cdc25 activation and MPF autoamplification in full grown oocytes is not expressed at the protein level in small stage IV oocytes. In order to determine if Plx1 could be the missing regulator that prevents MPF autoamplification, polo kinase was overexpressed in stage IV oocytes. Under these conditions, the MPF-positive feedback loop was restored. Moreover, we show that acquisition of autoamplification competence does not require the Mos/MAPK pathway.     

New ursolic and betulinic derivatives as potential cytotoxic agents

Fifteen new ursolic and betulinic triterpenoids, bearing various functionalities at C-3 and C-28 were synthesized as potential cytotoxic agents. All compounds were obtained by a hemisynthetic route via ursolic and betulinic acids. Preliminary screening of these compounds on human HT 29 colon cancer cells revealed inhibitory activity for three of them. Beta-D-Glucopyranosyl-3beta-hydroxyurs-12(13)-en-28-oate 1c, 3beta-3-(3-pyridyl)-prop-2-enoyloxyurs-12(13)-en-28-oic acid 1i and the potassium salt of 3beta-cinnamoyloxylup-20(29)-en-28-oic acid 2d demonstrated cytotoxic activity in the micromolar range: 8.0, 45.0 and 8.0 microM, respectively.     

Sequential FOLFIRI.3 + Gemcitabine Improves Health-Related Quality of Life Deterioration-Free Survival of Patients with Metastatic Pancreatic Adenocarcinoma: A Randomized Phase II Trial

BackgroundA randomized multicenter phase II trial was conducted to assess the sequential treatment strategy using FOLFIRI.3 and gemcitabine alternately (Arm 2) compared to gemcitabine alone (Arm 1) in patients with metastatic non pre-treated pancreatic adenocarcinoma. The primary endpoint was the progression-free survival (PFS) rate at 6 months. It concludes that the sequential treatment strategy appears to be feasible and effective with a PFS rate of 43.5% in Arm 2 at 6 months (26.1% in Arm 1). This paper reports the results of the longitudinal analysis of the health-related quality of life (HRQoL) as a secondary endpoint of this study.MethodsHRQoL was evaluated using the EORTC QLQ-C30 at baseline and every two months until the end of the study or death. HRQoL deterioration-free survival (QFS) was defined as the time from randomization to a first significant deterioration as compared to the baseline score with no further significant improvement, or death. A propensity score was estimated comparing characteristics of partial and complete responders. Analyses were repeated with inverse probability weighting method using the propensity score. Multivariate Cox regression analyses were performed to identify independent factors influencing QFS.Results98 patients were included between 2007 and 2011. Adjusting on the propensity score, patients of Arm 2 presented a longer QFS of Global Health Status (Hazard Ratio: 0.52 [0.31-0.85]), emotional functioning (0.35 [0.21–0.59]) and pain (0.50 [0.31 – 0.81]) than those of Arm 1.ConclusionPatients of Arm 2 presented a better HRQoL with a longer QFS than those of Arm 1. Moreover, the propensity score method allows to take into account the missing data depending on patients’ characteristics.

Trial registration information

Eudract N° 2006-005703-34. (Name of the Trial: FIRGEM).     

Value of Routine Dengue Diagnostic Tests in Urine and Saliva Specimens

BackgroundDengue laboratory diagnosis is essentially based on detection of the virus, its components or antibodies directed against the virus in blood samples. Blood, however, may be difficult to draw in some patients, especially in children, and sampling during outbreak investigations or epidemiological studies may face logistical challenges or limited compliance to invasive procedures from subjects. The aim of this study was to assess the possibility of using saliva and urine samples instead of blood for dengue diagnosis.ConclusionsAlthough the performances of the different diagnostic methods were not as good in saliva and urine as in plasma specimens, the results obtained by qRT-PCR and by anti-DENV antibody ELISA could well justify the use of these two body fluids to detect dengue infection in situations when the collection of blood specimens is not possible.     

Multicenter Testing of the Rapid Quantification of Radical Oxygen Species in Cerebrospinal Fluid to Diagnose Bacterial Meningitis

Purpose

Meningitis is a serious concern after traumatic brain injury (TBI) or neurosurgery. This study tested the level of reactive oxygen species (ROS) in cerebrospinal fluid (CSF) to diagnose meningitis in febrile patients several days after trauma or surgery.

Methods

Febrile patients (temperature > 38°C) after TBI or neurosurgery were included prospectively. ROS were measured in CSF within 4 hours after sampling using luminescence in the basal state and after cell stimulation with phorbol 12-myristate 13-acetate (PMA). The study was conducted in a single-center cohort 1 (n = 54, training cohort) and then in a multicenter cohort 2 (n = 136, testing cohort) in the Intensive Care and Neurosurgery departments of two teaching hospitals. The performance of the ROS test was compared with classical CSF criteria, and a diagnostic decision for meningitis was made by two blinded experts.

Results

The production of ROS was higher in the CSF of meningitis patients than in non-infected CSF, both in the basal state and after PMA stimulation. In cohort 1, ROS production was associated with a diagnosis of meningitis with an AUC of 0.814 (95% confidence interval (CI) [0.684–0.820]) for steady-state and 0.818 (95% CI [0.655–0.821]) for PMA-activated conditions. The best threshold value obtained in cohort 1 was tested in cohort 2 and showed high negative predictive values and low negative likelihood ratios of 0.94 and 0.36 in the basal state, respectively, and 0.96 and 0.24 after PMA stimulation, respectively.

Conclusion

The ROS test in CSF appeared suitable for eliminating a diagnosis of bacterial meningitis.