Oxidative stress induced by prenatal LPS leads to endothelial dysfunction and renal haemodynamic changes through angiotensin II/NADPH oxidase pathway: Prevention by early treatment with α-tocopherol

We investigated whether hypertension induced by maternal lipopolysaccharide (LPS) administration during gestation is linked to peripheral vascular and renal hemodynamic regulation, through angiotensin II?→?NADPH-oxidase signalling, and whether these changes are directly linked to intrauterine oxidative stress. Female Wistar rats were submitted to LPS, in the absence or presence of α-tocopherol during pregnancy. Malondialdehyde in placenta and in livers from dams and foetuses was enhanced by LPS. Tail-cuff systolic blood pressure (tcSBP) was elevated in the 16-week-old LPS offspring. Renal malondialdeyde and protein expression of NADPH oxidase isoform 2 were elevated in these animals at 20?weeks of age. Maternal α-tocopherol treatment prevented the elevation in malondialdehyde induced by LPS on placenta and livers from dams and foetuses, as well as prevented the elevation in tcSBP and the elevation in renal malondialdehyde in adult life. LPS offspring presented impairment of endothelium-dependent relaxation in aorta and mesenteric rings, which was blunted by angiotensin type 1 receptor (AT₁R) blockade and NADPH oxidase inhibition. At age of 32?weeks, renal hemodynamic parameters were unchanged in anaesthetised LPS offspring, but angiotensin II infusion led to an increased glomerular filtration rate paralleled by filtration fraction elevation. The renal haemodynamic changes provoked by angiotensin II was prevented by early treatment with α-tocopherol and by late treatment with NADPH oxidase inhibitor. These results point to oxidative stress as a mediator of offspring hypertension programmed by maternal inflammation and to the angiotensin II?→?NADPH oxidase signalling pathway as accountable for vascular and renal dysfunctions that starts and maintains hypertension.     

Fine Root Production across a Primary Successional Ecosystem Chronosequence at Mt. Shasta,California

Estimating changes in belowground biomass and production is essential for understanding fundamental patterns and processes during ecosystem development. We examined patterns of fine root production, aboveground litterfall, and forest floor accumulation during forest primary succession at the Mt. Shasta Mudflows ecosystem chronosequence. Fine root production was measured using the root ingrowth cores method over 1 year, and aboveground litterfall was collected over 2 years. Fine root production increased significantly with ecosystem age, but only the youngest ecosystem was significantly different from all of the older ecosystems. Root production was 44.5 ± 13.3, 168.3 ± 20.6, 190.5 ± 33.8, and 236.3 ± 65.4 g m⁻² y⁻¹ in the 77, 255, 616, and >850-year-old ecosystems, respectively. Generally, aboveground litterfall and forest floor accumulation did not follow the same pattern as root production. The relative contribution of fine root production to total fine detrital production increased significantly with ecosystem age, from 14 to 49%, but only the youngest ecosystem was significantly different from all of the older ecosystems. Fine root production was significantly correlated with some measures of soil fertility but was not correlated with leaf or total litterfall, or forest floor accumulation. It was best predicted by soil N concentration alone, but this relationship may not be causal, as soil N concentration was also correlated with ecosystem age. For the oldest ecosystem, fine root production was also measured using the sequential intact cores/compartment-flow model method, and the difference between the two estimates was not significant. Our study suggests that the relative contribution of fine roots to fine detrital production, and hence to soil organic matter accumulation, may increase during forest primary succession.     

Clinical infection in house rats (<Emphasis Type="Italic">Rattus rattus</Emphasis>) caused by <Emphasis Type="Italic">Streptobacillus notomytis</Emphasis>

Rat bite fever is an under-reported, under-diagnosed emerging zoonosis with worldwide distribution. Besides Spirillum minus, Streptobacillus moniliformis is the major causative microorganism although it usually colonises rats without any clinical signs. A group of house rats (Rattus rattus) kept in a zoo exhibition for educational purposes suffered from neurological signs including disorientation, torticollis, stall walking, ataxia and death. Gross pathological and histo-pathological examinations of the investigated rats revealed high-grade otitis interna et media, from which Streptobacillus notomytis was isolated in pure culture or as the predominant microorganism. This case series underlines a previously expressed hypothesis that R. rattus might be naturally colonised with S. notomytis, whereas the traditional rat bite fever organism, S. moniliformis, might be restricted to the Norway rat (Rattus norvegicus). However, the general paucity of Streptobacillus isolates, especially from their respective animal hosts, precludes definitive proof of these host tropisms. This is the first report of S. notomytis detection outside Asia and Australia and the first evidence for its role as a facultative pathogen in house rats.     

Diversification,evolution and methylation of short interspersed nuclear element families in sugar beet and related Amaranthaceae species

Short interspersed nuclear elements (SINEs) are non‐autonomous non‐long terminal repeat retrotransposons which are widely distributed in eukaryotic organisms. While SINEs have been intensively studied in animals, only limited information is available about plant SINEs. We analysed 22 SINE families from seven genomes of the Amaranthaceae family and identified 34 806 SINEs, including 19 549 full‐length copies. With the focus on sugar beet (Beta vulgaris), we performed a comparative analysis of the diversity, genomic and chromosomal organization and the methylation of SINEs to provide a detailed insight into the evolution and age of Amaranthaceae SINEs. The lengths of consensus sequences of SINEs range from 113 nucleotides (nt) up to 224 nt. The SINEs show dispersed distribution on all chromosomes but were found with higher incidence in subterminal euchromatic chromosome regions. The methylation of SINEs is increased compared with their flanking regions, and the strongest effect is visible for cytosines in the CHH context, indicating an involvement of asymmetric methylation in the silencing of SINEs.     

Posttraumatic Stress Disorder (PTSD) Patients Exhibit a Blunted Parasympathetic Response to an Emotional Stressor

Diminished parasympathetic reactivity is a physiological feature of posttraumatic stress disorder (PTSD). The objective of this study was to compare female PTSD patients with non-traumatized healthy women with respect to autonomic cardiovascular regulation during exposure to two stressors. Hospitalized PTSD patients (n = 52) and controls (n = 37) completed standardized laboratory-based stress testing including a mental arithmetic test and a standardized audiotape recording of a crying infant. Controls and PTSD patients both showed a significantly increased heart rate and reduced pre-ejection period from baseline rest to the arithmetic stressor. However, as judged from nonsignificant changes in baroreflex sensitivity, parasympathetic activation caused by the crying infant stressor was blunted in PTSD patients as compared to healthy individuals. Under the crying infant condition, a vagal dominance was observed only in controls, and not in PTSD patients. Our data demonstrate that, in PTSD patients, diminished parasympathetic reactivity is not restricted to trauma-related events but can also be observed in response to a social stimulus such as listening to a crying infant. This finding suggests that the altered vagal reactivity in PTSD patients reflects the physiological consequences of a generally disturbed autonomous response to emotionally relevant stressors.     

Expression and characterization of a human BMP-7 variant with improved biochemical properties

Bone morphogenetic protein-7 (BMP-7, OP-1) is a secreted growth factor that is predominantly known for its osteoinductive properties, though it has also been implicated as having a role in mammalian kidney development. Clinical efficacy of recombinant BMP-7 has been demonstrated in the treatment of orthopedic injuries through topical application. However, the pharmaceutical development of recombinant BMP-7 for systemic delivery has presented many challenges. Specifically, the expression level of recombinant mature BMP-7 protein in mammalian cells is very low, the molecule has poor solubility at neutral pH, and intracellular proteolytic processing events result in a secreted BMP-7 having multiple amino-termini, creating a heterogeneous mixture of proteins. Utilizing structural information, we have designed and generated a number of rational BMP-7 mutations that improved both expression levels in mammalian cells and solubility at neutral pH, while limiting the amino-terminal heterogeneity of the mature protein. Introduction of these mutations did not compromise BMP-7 in vitro bioactivity. This improved BMP-7 molecule is better suited for pharmaceutical development and clinical advancement for indications where systemic delivery may be required.     

Diversity and beyond: plant functional identity determines herbivore performance

1. Recent biodiversity studies have addressed various community-level effects of biodiversity change, but the number of studies on specific biotic interactions is still rather limited. An open question in the context of plant-insect-herbivore relationships is how diversity impacts the population ecology of individual species. 2. In the present study, we explored the relationship between plant species diversity and the performance and fitness of a generalist herbivore, the meadow grasshopper Chorthippus parallelus Zetterstedt (Orthoptera, Gomphocerinae). A total of 1620 fourth-instar nymphs of this insect were captured and transferred to cages (10 females and 10 males per cage) on 81 experimental grassland communities in plots containing one to 60 plant species within the Jena biodiversity experiment. 3. Median survival of grasshoppers in the experiment was 14.5 days. Survival was independent of plant species richness and number of plant functional groups in the communities, but increased if plant communities contained grasses. Plant species richness and plant functional group richness had no effect on the number of oothecae laid by females or the number of hatchlings in the next generation. 4. Functional group composition of the plant communities affected most fitness measures. Grass presence increased the number of oothecae laid by females from 0.78 +/- 0.21 to 3.7 +/- 0.41 per female, and the number of hatchlings in the next generation from 4.0 +/- 1.3 to 16.6 +/- 2.4. Certain combinations of plant functional groups increased grasshopper survival. 5. The findings indicate that the fitness of C. parallelus is influenced more by plant functional group identity than by plant species richness. In the absence of grasses, grasshoppers performed better if more than just one functional group of plants was present. We call this a 'rescue effect' of plant functional group richness.