Myocardial dysfunction and septic shock

Myocardial dysfunction frequently accompanies severe sepsis and septic shock. It is now clear that such a myocardial depression, as evidenced by biventricular alteration, is present during the early phase of sepsis in most patients. Myocardial depression exists despite a fluid loading-dependent hyperdynamic state and usually recovers within 7 to 10 days in survivors. Myocardial dysfunction does not appear to be due to irreversible structural abnormalities nor to myocardial hypoperfusion, but rather linked to many circulating mediators including cytokines. At a cellular level, reduced myocardial contractility could be related in part to apoptosis and induced by both nitric oxide-dependent and nitric oxide-independent mechanisms. However, whatever the mechanism involved, it leads to calcium homeostasis abnormality. The present review describes both the diagnosis procedure and the molecular and cellular pathways of sepsis-induced myocardial depression.     

Dinucleotide spore photoproduct, a minimal substrate of the DNA repair spore photoproduct lyase enzyme from Bacillus subtilis

The overwhelming majority of DNA photoproducts in UV-irradiated spores is a unique thymine dimer called spore photoproduct (SP, 5-thymine-5,6-dihydrothymine). This lesion is repaired by the spore photoproduct lyase (SP lyase) enzyme that directly reverts SP to two unmodified thymines. The SP lyase is an S-adenosylmethionine-dependent iron-sulfur protein that belongs to the radical S-adenosylmethionine superfamily. In this study, by using a well characterized preparation of the SP lyase enzyme from Bacillus subtilis, we show that SP in the form of a dinucleoside monophosphate (spore photoproduct of thymidilyl-(3'-5')-thymidine) is efficiently repaired, allowing a kinetic characterization of the enzyme. The preparation of this new substrate is described, and its identity is confirmed by mass spectrometry and comparison with authentic spore photoproduct. The fact that the spore photoproduct of thymidilyl-(3'-5')-thymidine dimer is repaired by SP lyase may indicate that the SP lesion does not absolutely need to be contained within a single- or double-stranded DNA for recognition and repaired by the SP lyase enzyme.     

DNA repair and free radicals, new insights into the mechanism of spore photoproduct lyase revealed by single amino acid substitution

The major DNA photoproduct in UV-irradiated Bacillus subtilis spores is the thymine dimer named spore photoproduct (SP, 5-(alpha-thyminyl)-5,6-dihydrothymine). The SP lesion has been found to be efficiently repaired by SP lyase (SPL) a very specific enzyme that reverses the SP to two intact thymines, at the origin of the great resistance of the spores to UV irradiation. SPL belongs to a superfamily of [4Fe-4S] iron-sulfur enzymes, called "Radical-SAM." Here, we show that the single substitution of cysteine 141 into alanine, a residue fully conserved in Bacillus species and previously shown to be essential for spore DNA repair in vivo, has a major impact on the outcome of the SPL-dependent repair reaction in vitro. Indeed the modified enzyme catalyzes the almost quantitative conversion of the SP lesion into one thymine and one thymine sulfinic acid derivative. This compound results from the trapping of the allyl-type radical intermediate by dithionite, used as reducing agent in the reaction mixture. Implications of the data reported here regarding the repair mechanism and the role of Cys-141 are discussed.     

Effects of penitrem A on rat's performances in passive avoidance and Morris water maze tests

Intraperitoneal administration of the mycotoxin penitrem A 30 min before a training session in passive avoidance task, impaired performance of rats subjected to a test-session 24 h after. This effect was not antagonised by pretraining administration of physostigmine or bicuculline. Administration of penitrem A 20 min before a training session or 30 min before a test-session did not impair performance. In the Morris water maze, doses of penitrem A that induces slight to moderate tremors, but not a lower dose, disrupted place learning. These results suggest that penitrem A disrupts the processes that take place at the time of acquisition, but not those just after acquisition, and does not alter the restitution of information. This effect would not be related to a decrease of cholinergic neurotransmission nor to a stimulation of GABA A receptors. Nevertheless, it could not be totally excluded that the performance impairments induced by penitrem A would be secondary to a motor disruption. This revised version was published online in June 2006 with corrections to the Cover Date.     

Identifying climatic niche shifts using coarse‐grained occurrence data: a test with non‐native freshwater fish

Aim We tested whether coarse‐grained occurrence data can be used to detect climatic niche shifts between native and non‐native ranges for a set of widely introduced freshwater fishes. Location World‐wide. Methods We used a global database of freshwater fish occurrences at the river basin scale to identify native and non‐native ranges for 18 of the most widely introduced fish species. We also examined climatic conditions within each river basin using fine‐grained climate data. We combined this information to test whether climatic niche shifts have occurred between native and non‐native ranges. We defined climatic niche shifts as instances where the ranges of a climatic variable within native and non‐native basins exhibit zero overlap. Results We detected at least one climatic niche shift for each of the 18 studied species. However, we did not detect common patterns in the thermal preference or biogeographic origin of the non‐native fish, hence suggesting a species‐specific response. Main conclusions Coarse‐grained occurrence data can be used to detect climatic niche shifts. They also enable the identification of the species experiencing niche shifts, although the mechanisms responsible for these shifts (e.g. local adaptation, dispersal limitation or physiological constraints) have yet to be determined. Furthermore, the coarse‐grained approach, which highlights regions where climatic niche shifts have occurred, can be used to select specific river basins for more detailed, fine‐grained studies.     

Characterization of a two-component high-affinity nitrate uptake system in Arabidopsis. Physiology and protein-protein interaction

The identification of a family of NAR2-type genes in higher plants showed that there was a homolog in Arabidopsis (Arabidopsis thaliana), AtNAR2.1. These genes encode part of a two-component nitrate high-affinity transport system (HATS). As the Arabidopsis NRT2 gene family of nitrate transporters has been characterized, we tested the idea that AtNAR2.1 and AtNRT2.1 are partners in a two-component HATS. Results using the yeast split-ubiquitin system and Xenopus oocyte expression showed that the two proteins interacted to give a functional HATS. The growth and nitrogen (N) physiology of two Arabidopsis gene knockout mutants, atnrt2.1-1 and atnar2.1-1, one for each partner protein, were compared. Both types of plants had lost HATS activity at 0.2 mm nitrate, but the effect was more severe in atnar2.1-1 plants. The relationship between plant N status and nitrate transporter expression revealed a pattern that was characteristic of N deficiency that was again stronger in atnar2.1-1. Plants resulting from a cross between both mutants (atnrt2.1-1 x atnar2.1-1) showed a phenotype like that of the atnar2.1-1 mutant when grown in 0.5 mm nitrate. Lateral root assays also revealed growth differences between the two mutants, confirming that atnar2.1-1 had a stronger phenotype. To show that the impaired HATS did not result from the decreased expression of AtNRT2.1, we tested if constitutive root expression of a tobacco (Nicotiana plumbaginifolia) gene, NpNRT2.1, previously been shown to complement atnrt2.1-1, can restore HATS to the atnar2.1-1 mutant. These plants did not recover wild-type nitrate HATS. Taken together, these results show that AtNAR2.1 is essential for HATS of nitrate in Arabidopsis.     

Accounting for heterogeneity when estimating stopover duration,timing and population size of red knots along the Luannan Coast of Bohai Bay,China

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The Arabidopsis TONNEAU2 gene encodes a putative novel protein phosphatase 2A regulatory subunit essential for the control of the cortical cytoskeleton

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