Bifidobacteria-mediated immune system imprinting early in life

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Carbon catabolite repression in <Emphasis Type="Italic">Thermoanaerobacterium saccharolyticum</Emphasis>

Background

The thermophilic anaerobe Thermoanaerobacterium saccharolyticum is capable of directly fermenting xylan and the biomass-derived sugars glucose, cellobiose, xylose, mannose, galactose and arabinose. It has been metabolically engineered and developed as a biocatalyst for the production of ethanol.

Results

We report the initial characterization of the carbon catabolite repression system in this organism. We find that sugar metabolism in T. saccharolyticum is regulated by histidine-containing protein HPr. We describe a mutation in HPr, His15Asp, that leads to derepression of less-favored carbon source utilization.

Conclusion

Co-utilization of sugars can be achieved by mutation of HPr in T. saccharolyticum. Further manipulation of CCR in this organism will be instrumental in achieving complete and rapid conversion of all available sugars to ethanol.

     

Intracellular Conversion of Environmental Nitrate and Nitrite to Nitric Oxide with Resulting Developmental Toxicity to the Crustacean Daphnia magna

Background

Nitrate and nitrite (jointly referred to herein as NO_x) are ubiquitous environmental contaminants to which aquatic organisms are at particularly high risk of exposure. We tested the hypothesis that NO_x undergo intracellular conversion to the potent signaling molecule nitric oxide resulting in the disruption of endocrine-regulated processes.

Methodology/Principal Findings

These experiments were performed with insect cells (Drosophila S2) and whole organisms Daphnia magna. We first evaluated the ability of cells to convert nitrate (NO₃ ⁻) and nitrite (NO₂ ⁻) to nitric oxide using amperometric real-time nitric oxide detection. Both NO₃ ⁻ and NO₂ ⁻ were converted to nitric oxide in a substrate concentration-dependent manner. Further, nitric oxide trapping and fluorescent visualization studies revealed that perinatal daphnids readily convert NO₂ ⁻ to nitric oxide. Next, daphnids were continuously exposed to concentrations of the nitric oxide-donor sodium nitroprusside (positive control) and to concentrations of NO₃ ⁻ and NO₂ ⁻. All three compounds interfered with normal embryo development and reduced daphnid fecundity. Developmental abnormalities were characteristic of those elicited by compounds that interfere with ecdysteroid signaling. However, no compelling evidence was generated to indicate that nitric oxide reduced ecdysteroid titers.

Conclusions/Significance

Results demonstrate that nitrite elicits developmental and reproductive toxicity at environmentally relevant concentrations due likely to its intracellular conversion to nitric oxide.     

Development of restoration techniques for Hawaiian thrushes: Collection of wild eggs,artificial incubation,hand‐rearing,captive‐breeding,and re‐introduction to the wild

From 1995 to 1999, two species of endemic Hawaiian thrushes, `Oma`o (Myadestes obscurus) and Puaiohi (M. palmeri), were captive‐reared and re‐introduced into their historic range in Hawai`i by The Peregrine Fund, in collaboration with the U.S. Geological Survey–Biological Resources Division (BRD) and the Hawai`i State Department of Land and Natural Resources. This paper describes the management techniques that were developed (collection of wild eggs, artificial incubation, hand‐rearing, captive propagation, and release) with the non‐endangered surrogate species, the `Oma`o; techniques that are now being used for recovery of the endangered Puaiohi. In 1995 and 1996, 29 viable `Oma`o eggs were collected from the wild. Of 27 chicks hatched, 25 were hand‐reared and released into Pu`u Wa`awa`a Wildlife Reserve. Using the techniques developed for the `Oma`o, a captive propagation and release program was initiated in 1996 to aid the recovery of the endangered Puaiohi. Fifteen viable Puaiohi eggs were collected from the wild (1996–1997) to establish a captive breeding flock to produce birds for re‐introduction. These Puaiohi reproduced for the first time in captivity in 1998 (total Puaiohi chicks reared in captivity 1996–1998 = 41). In 1999, 14 captive‐bred Puaiohi were re‐introduced into the Alaka`i Swamp, Kaua`i. These captive‐bred birds reproduced and fledged seven chicks in the wild after release. This is the first endangered passerine recovery program using this broad spectrum of management techniques (collection of wild eggs, artificial incubation, hand‐rearing, captive‐breeding, and release) in which re‐introduced birds survived and bred in the wild. Long‐term population monitoring will be published separately [BRD, in preparation]. Zoo Biol 19:263–277, 2000. © 2000 Wiley‐Liss, Inc.     

Effect of changes in arterial oxygen content on circulation and physical performance.

To evaluate the effect of different levels of arterial oxygen content on hemodynamic parameters during exercise nine subjects performed submaximal bicycle or treadmill exercise and maximal treadmill exercise under three different experimental conditions: 1) breathing room air (control); 2) breathing 50% oxygen (hyperoxia); 3) after rebreathing a carbon monoxide gas mixture (hypoxia). Maximal oxygen consumption (Vo2 max) was significantly higher in hyperoxia (4.99 1/min) and significantly lower in hypoxia (3.80 1/min) than in the control experiment (4.43 1/min). Physical performance changes in parallel with Vo2 max. Maximal cardiac output (Qmax) was similar in hyperoxia as in control but was significantly lower in hypoxia mainly due to a decreased stroke volume. A correlation was found between Vo2 max and transported oxygen, i.e., Cao2 times Amax, thus suggesting that central circulation is an important limiting factor for human maximal aerobic power. During submaximal work HR was decreased in hyperoxia and increased in hypoxia. Corresponding Q values were unchanged except for a reduction during high submaximal exercise in hyperoxia.     

Quinazolinones as γ-secretase modulators

Synthesis, SAR and evaluation of styrenyl quinazolinones as novel gamma secretase modulators are presented in this communication. Starting from literature and in-house leads we evaluated a range of quinazolinones which showed good modulation of γ-secretase activity.     

Toxoplasma gondii chromodomain protein 1 binds to heterochromatin and colocalises with centromeres and telomeres at the nuclear periphery

Background

Apicomplexan parasites are responsible for some of the most deadly parasitic diseases afflicting humans, including malaria and toxoplasmosis. These obligate intracellular parasites exhibit a complex life cycle and a coordinated cell cycle-dependant expression program. Their cell division is a coordinated multistep process. How this complex mechanism is organised remains poorly understood.

Methods and Findings

In this study, we provide evidence for a link between heterochromatin, cell division and the compartmentalisation of the nucleus in Toxoplasma gondii. We characterised a T. gondii chromodomain containing protein (named TgChromo1) that specifically binds to heterochromatin. Using ChIP-on-chip on a genome-wide scale, we report TgChromo1 enrichment at the peri-centromeric chromatin. In addition, we demonstrate that TgChromo1 is cell-cycle regulated and co-localised with markers of the centrocone. Through the loci-specific FISH technique for T. gondii, we confirmed that TgChromo1 occupies the same nuclear localisation as the peri-centromeric sequences.

Conclusion

We propose that TgChromo1 may play a role in the sequestration of chromosomes at the nuclear periphery and in the process of T. gondii cell division.