Imbalance of leucine flux in Lactococcus lactis and its use for the isolation of diacetyl-overproducing strains.

Diacetyl is a by-product of pyruvate metabolism in Lactococcus lactis, where pyruvate is first converted to alpha-acetolactate, which is slowly decarboxylated to diacetyl in the presence of oxygen. L. lactis usually converts alpha-acetolactate to acetoin enzymatically, by alpha-acetolactate decarboxylase encoded by the aldB gene. We took advantage of the fact that this enzyme also has a central role in the regulation of branched-chain amino acids, to select spontaneous aldB mutants in an unbalanced concentration of leucine versus those of valine and isoleucine in the medium. Industrial dairy strains of L. lactis subsp. lactis biovar diacetylactis containing point mutations and deletions of aldB were isolated and characterized. Their growth in milk was not affected, but they rapidly accumulated a large amount of alpha-acetolactate instead of acetoin from citrate in milk. Under aerated condition, strains devoid of AldB produced about 10 times more diacetyl than did the parental strains.     

Survival of yogurt bacteria in the human gut

Whether Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus can be recovered after passage through the human gut was tested by feeding 20 healthy volunteers commercial yogurt. Yogurt bacteria were found in human feces, suggesting that they can survive transit in the gastrointestinal tract.     

Survival of Yogurt Bacteria in the Human Gut

Whether Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus can be recovered after passage through the human gut was tested by feeding 20 healthy volunteers commercial yogurt. Yogurt bacteria were found in human feces, suggesting that they can survive transit in the gastrointestinal tract.     

Exposure of Vicia faba and Pisum sativum to copper-induced genotoxicity

The potential genotoxicity of Cu(2+) was investigated in Vicia faba and Pisum sativum seedlings in hydroponic culture conditions. Cu(2+) caused a dose-dependent increase in micronuclei frequencies in both plant models. Cytological analysis of root tips cells showed clastogenic and aneugenic effects of this heavy metal on V. faba root meristems. Cu(2+) induced chromosomal alterations at the lowest concentration used (2.5 mM) when incubated for 42 h, indicating the potent mutagenic effect of this ion. A spectrum of chromosomal abnormalities was observed in V. faba root meristems, illustrating the genotoxic events leading to micronuclei formation.     

A Novel Biased Allosteric Compound Inhibitor of Parturition Selectively Impedes the Prostaglandin F2α-mediated Rho/ROCK Signaling Pathway

The prostaglandin F2α (PGF2α) receptor (FP) is a key regulator of parturition and a target for pharmacological management of preterm labor. However, an incomplete understanding of signaling pathways regulating myometrial contraction hinders the development of improved therapeutics. Here we used a peptidomimetic inhibitor of parturition in mice, PDC113.824, whose structure was based on the NH₂-terminal region of the second extracellular loop of FP receptor, to gain mechanistic insight underlying FP receptor-mediated cell responses in the context of parturition. We show that PDC113.824 not only delayed normal parturition in mice but also that it inhibited both PGF2α- and lipopolysaccharide-induced preterm labor. PDC113.824 inhibited PGF2α-mediated, Gα₁₂-dependent activation of the Rho/ROCK signaling pathways, actin remodeling, and contraction of human myometrial cells likely by acting as a non-competitive, allosteric modulator of PGF2α binding. In contrast to its negative allosteric modulating effects on Rho/ROCK signaling, PDC113.824 acted as a positive allosteric modulator on PGF2α-mediated protein kinase C and ERK1/2 signaling. This bias in receptor-dependent signaling was explained by an increase in FP receptor coupling to Gα_q, at the expense of coupling to Gα₁₂. Our findings regarding the allosteric and biased nature of PDC113.824 offer new mechanistic insights into FP receptor signaling relevant to parturition and suggest novel therapeutic opportunities for the development of new tocolytic drugs.     

Identification of Agrostis tenuis leaf proteins in response to As(V) and As(III) induced stress using a proteomics approach

Agrostis tenuis is known to be able to metabolise arsenate (As(V)) and arsenite (As(III)) which are toxic salts for most plants. A proteomic approach was developed to identify proteins expressed in response to treatments with these salts. A. tenuis plants were grown hydroponically in the presence of 134 and 668 μM As(V) or As(III) for 8 days at pH 7. During arsenic treatments, leaves showed chlorotic symptoms but fresh and dry leaf weights were not reduced, except in the presence of 668 μM As(III). On the contrary, a slight increase in biomass was observed with high As(V) concentrations. Thus, A. tenuis was more sensitive to As(III) than to As(V) and biomass was affected. Proteomic analysis enabled identification of a set of A. tenuis leaf proteins differentially expressed in response to arsenic exposure including a major functionally homogeneous group of enzymes such as oxygen-evolving enhancer protein, RuBisCO small and large subunits, RuBisCO activase and ATP synthase involved in the Calvin or Krebs cycle. The adaptative response to treatments resulted in partial disruption of the photosynthetic processes with prominent fragmentation of the RubisCO. Other proteins expressed differently from controls were identified and are possibly involved in the tolerance mechanisms of A. tenuis to arsenic treatments.     

Home Non-Invasive Ventilation Fails to Improve Quality of Life in the Elderly: Results from a Multicenter Cohort Study

BackgroundHome non-invasive ventilation (NIV) is a widely used treatment for chronic hypoventilation but little is known on its impact in the elderly. In a multicenter prospective cohort study, we studied tolerance and efficacy of domiciliary NIV in patients aged 75 or more compared to younger ones.ConclusionNIV was efficient in the elderly while evaluation at 6 months showed a good adherence but failed to improve HRQL.