Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae

Aging is believed to be a nonadaptive process that escapes the force of natural selection. Here, we challenge this dogma by showing that yeast laboratory strains and strains isolated from grapes undergo an age- and pH-dependent death with features of mammalian programmed cell death (apoptosis). After 90-99% of the population dies, a small mutant subpopulation uses the nutrients released by dead cells to grow. This adaptive regrowth is inversely correlated with protection against superoxide toxicity and life span and is associated with elevated age-dependent release of nutrients and increased mutation frequency. Computational simulations confirm that premature aging together with a relatively high mutation frequency can result in a major advantage in adaptation to changing environments. These results suggest that under conditions that model natural environments, yeast organisms undergo an altruistic and premature aging and death program, mediated in part by superoxide. The role of similar pathways in the regulation of longevity in organisms ranging from yeast to mice raises the possibility that mammals may also undergo programmed aging.     

Kinematic and kinetic features of normal level walking in patellofemoral pain syndrome: More than a sagittal plane alteration

Patients with patellofemoral pain syndrome (PFPS) often report discomfort and pain during walking. To date, most of the studies conducted to determine gait alterations in PFPS patients have focused on sagittal plane alterations. Physiological and biomechanical factors, however, suggest that frontal and transverse plane alterations may be involved in PFPS. We therefore decided to conduct a kinematic and kinetic evaluation on all three planes in 9 PFPS subjects and 9 healthy sex- and age-matched controls. General gait characteristics were similar in patients and controls, with the exception of swing velocity, which was lower in PFPS patients. Patients also displayed an increased knee abductor and external rotator moments in loading response, and reduced knee extensor moment both in loading response and in terminal stance. We speculate that these findings may be linked both to a pain-avoiding gait pattern and to alterations in the timing of activation of different components of the quadriceps muscle, which is typical of PFPS. The relevance for clinicians is this gait pattern may represent a biomechanical risk factor for future knee osteoarthritis. We therefore recommend that treatments aimed at PFPS should also attempt to restore a correct walking pattern.     

Properties of sesame oil by detailed 1H and 13C NMR assignments before and after ozonation and their correlation with iodine value,peroxide value,and viscosity measurements

Gaseous ozone chemically reacts with unsaturated triglyceride substrates leading to ozonated derivatives with a wide potential applications, ranging from the petrochemical to the pharmaceutical industry. To date, an ultimate understanding of the ozone reactivity during sesame oil ozonation process as well as detailed ¹H and ¹³C NMR assignments are lacking. A practical advantage of NMR is that a single NMR sample measurement can explain many issues, while similar analysis by traditional methods may require several independent and time-consuming measurements. Moreover, significant relationships among NMR spectra and both conventional chemical analysis and viscosity measurements have been found. Eventually, NMR could play an important role for quality attributes of ozonated oil derivatives.     

Anaerobic Bioremediation of Groundwater Containing a Mixture of 1,1,2,2-Tetrachloroethane and Chloroethenes

This study investigated the biotransformation pathways of 1,1,2,2-tetrachloroethane (1,1,2,2-TeCA) in the presence of chloroethenes (i.e. tetrachloroethene, PCE; trichloroethene, TCE) in anaerobic microcosms constructed with subsurface soil and groundwater from a contaminated site. When amended with yeast extract, lactate, butyrate, or H₂ and acetate, 1,1,2,2-TeCA was initially dechlorinated via both hydrogenolysis to 1,1,2-trichloroethane (1,1,2-TCA) (major pathway) and dichloroelimination to dichloroethenes (DCEs) (minor pathway), with both reactions occurring under sulfidogenic conditions. In the presence of only H₂, the hydrogenolysis of 1,1,2,2-TeCA to 1,1,2-TCA apparently required the presence of acetate to occur. Once formed, 1,1,2-TCA was degraded predominantly via dichloroelimination to vinyl chloride (VC). Ultimately, chloroethanes were converted to chloroethenes (mainly VC and DCEs) which persisted in the microcosms for very long periods along with PCE and TCE originally present in the groundwater. Hydrogenolysis of chloroethenes occurred only after highly reducing methanogenic conditions were established. However, substantial conversion to ethene (ETH) was observed only in microcosms amended with yeast extract (200 mg/l), suggesting that groundwater lacked some nutritional factors which were likely provided to dechlorinating microorganisms by this complex organic substrate. Bioaugmentation with an H₂-utilizing PCE-dechlorinating Dehalococcoides spp. -containing culture resulted in the conversion of 1,1,2,2-TeCA, PCE and TCE to ETH and VC. No chloroethanes accumulated during degradation suggesting that 1,1,2,2-TeCA was degraded through initial dichloroelimination into DCEs and then typical hydrogenolysis into ETH and VC.     

TP53 and p16INK4A, but not H-KI-Ras, are involved in tumorigenesis and progression of pleomorphic adenomas

The putative role of TP53 and p16(INK4A) tumor suppressor genes and Ras oncogenes in the development and progression of salivary gland neoplasias was studied in 28 cases of pleomorphic adenomas (PA), 4 cases of cystic adenocarcinomas, and 1 case of carcinoma ex-PA. Genetic and epigenetic alterations in the above genes were analyzed by Polymerase Chain Reaction/Single Strand Conformational Polymorphism (PCR/SSCP) and sequencing and by Methylation Specific-PCR (MS-PCR). Mutations in TP53 were found in 14% (4/28) of PAs and in 60% (3/5) of carcinomas. Mutations in H-Ras and K-Ras were identified in 4% (1/28) and 7% (2/28) of PAs, respectively. Only 20% (1/5) of carcinomas screened displayed mutations in K-Ras. p16(INK4A) promoter hypermethylation was found in 14% (4/28) of PAs and 100% (5/5) carcinomas. All genetic and epigenetic alterations were detected exclusively in the epithelial and transitional tumor components, and were absent in the mesenchymal parts. Our analysis suggests that TP53 mutations and p16(INK4A) promoter methylation, but not alterations in the H-Ras and K-Ras genes, might be involved in the malignant progression of PA into carcinoma.     

A realistic evaluation of the action of ozone on whole human blood

We have clarified the role of the ozone concentration in relation to the resistance of human erythrocytes in whole human blood or in blood diluted either in saline or in distilled water.

Spectrophotometric data related to haemoglobin were evaluated by exposing samples of fresh human blood directly to ozone doses (ratio 1:1 volume), within the therapeutic range (0.21–1.68 mM) and to one toxic dose (3.36 mM). Furthermore, the same determinations have been carried out after previous dilution of the same blood with either pure water or physiological saline (1 ml blood + 29 ml diluent) followed by ozonation with the above reported ozone doses. Addition of either saline or water implies a dilution of plasma antioxidants and also total haemolysis after water dilution. Particularly the latter case represents a most unphysiological situation because the osmotic shock causes the solubilization of the erythrocytic content. While it is possible to demonstrate that after haemolysis there is an ozone-concentration dependent transformation of some oxyhaemoglobin to methaemoglobin, no such process occurs after ozonation of whole blood.

The results of this study fully confirm our previous data that judicious ozone doses neither damage erythrocytes, nor induce oxidation of intracellular haemoglobin. We hope that our conclusions will definitively clarify the absence of toxicity of ozonetherapy.     

Genome Sequence of “Candidatus Microthrix parvicella” Bio17-1, a Long-Chain-Fatty-Acid-Accumulating Filamentous Actinobacterium from a Biological Wastewater Treatment Plant

“Candidatus Microthrix” bacteria are deeply branching filamentous actinobacteria which occur at the water-air interface of biological wastewater treatment plants, where they are often responsible for foaming and bulking. Here, we report the first draft genome sequence of a strain from this genus: “Candidatus Microthrix parvicella” strain Bio17-1.     

High-fat diets rich in soy or fish oil distinctly alter hypothalamic insulin signaling in rats

Hypothalamic insulin inhibits food intake, preventing obesity. High-fat feeding with polyunsaturated fats may be obesogenic, but their effect on insulin action has not been elucidated. The present study evaluated insulin hypophagia and hypothalamic signaling after central injection in rats fed either control diet (15% energy from fat) or high-fat diets (50% energy from fat) enriched with either soy or fish oil. Soy rats had increased fat pad weight and serum leptin with normal body weight, serum lipid profile and peripheral insulin sensitivity. Fish rats had decreased body and fat pad weight, low leptin and corticosterone levels, and improved serum lipid profile. A 20-mU dose of intracerebroventricular (ICV) insulin inhibited food intake in control and fish groups, but failed to do so in the soy group. Hypothalamic protein levels of IR, IRS-1, IRS-2, Akt, mTOR, p70S6K and AMPK were similar among groups. ICV insulin stimulated IR tyrosine phosphorylation in control (68%), soy (36%) and fish (34%) groups. Tyrosine phosphorylation of the pp185 band was significantly stimulated in control (78%) and soy (53%) rats, but not in fish rats. IRS-1 phosphorylation was stimulated only in control rats (94%). Akt serine phosphorylation was significantly stimulated only in control (90%) and fish (78%) rats. The results showed that, rather than the energy density, the fat type was a relevant aspect of high-fat feeding, since blockade of hypothalamic insulin signal transmission and insulin hypophagia was promoted only by the high-fat soy diet, while they were preserved in the rats fed with the high-fat fish diet.     

Theoretical and experimental evidence of the photonitration pathway of phenol and 4-chlorophenol: a mechanistic study of environmental significance

Light-induced nitration pathways of phenols are important processes for the transformation of pesticide-derived secondary pollutants into toxic derivatives in surface waters and for the formation of phytotoxic compounds in the atmosphere. Moreover, phenols can be used as ˙NO(2) probes in irradiated aqueous solutions. This paper shows that the nitration of 4-chlorophenol (4CP) into 2-nitro-4-chlorophenol (NCP) in the presence of irradiated nitrate and nitrite in aqueous solution involves the radical ˙NO(2). The experimental data allow exclusion of an alternative nitration pathway by ˙OH + ˙NO(2). Quantum mechanical calculations suggest that the nitration of both phenol and 4CP involves, as a first pathway, the abstraction of the phenolic hydrogen by ˙NO(2), which yields HNO(2) and the corresponding phenoxy radical. Reaction of phenoxyl with another ˙NO(2) follows to finally produce the corresponding nitrated phenol. Such a pathway also correctly predicts that 4CP undergoes nitration more easily than phenol, because the ring Cl atom increases the acidity of the phenolic hydrogen of 4CP. This favours the H-abstraction process to give the corresponding phenoxy radical. In contrast, an alternative nitration pathway that involves ˙NO(2) addition to the ring followed by H-abstraction by oxygen (or by ˙NO(2) or ˙OH) is energetically unfavoured and erroneously predicts faster nitration for phenol than for 4CP.