Hyperactivation of retina by light in mice leads to photoreceptor cell death mediated by VEGF and retinal pigment epithelium permeability.

Light toxicity is suspected to enhance certain retinal degenerative processes such as age-related macular degeneration. Death of photoreceptors can be induced by their exposure to the visible light, and although cellular processes within photoreceptors have been characterized extensively, the role of the retinal pigment epithelium (RPE) in this model is less well understood. We demonstrate that exposition to intense light causes the immediate breakdown of the outer blood-retinal barrier (BRB). In a molecular level, we observed the slackening of adherens junctions tying up the RPE and massive leakage of albumin into the neural retina. Retinal pigment epithelial cells normally secrete vascular endothelial growth factor (VEGF) at their basolateral side; light damage in contrast leads to VEGF increase on the apical side - that is, in the neuroretina. Blocking VEGF, by means of lentiviral gene transfer to express an anti-VEGF antibody in RPE cells, inhibits outer BRB breakdown and retinal degeneration, as illustrated by functional, behavioral and morphometric analysis. Our data show that exposure to high levels of visible light induces hyperpermeability of the RPE, likely involving VEGF signaling. The resulting retinal edema contributes to irreversible damage to photoreceptors. These data suggest that anti-VEGF compounds are of therapeutic interest when the outer BRB is altered by retinal stresses.

Biological embedding of early-life exposures and disease risk in humans : a role for DNA methylation

BACKGROUND: Following wider acceptance of 'the thrifty phenotype' hypothesis and the convincing evidence that early-life exposures can influence adult health even decades after the exposure, much interest has been placed on the mechanisms through which early-life exposures become biologically embedded. MATERIALS AND METHODS: In this review, we summarize the current literature regarding biological embedding of early-life experiences. To this end, we conducted a literature search to identify studies investigating early-life exposures in relation to DNA methylation changes. In addition, we summarize the challenges faced in investigations of epigenetic effects, stemming from the peculiarities of this emergent and complex field. A proper systematic review and meta-analyses were not feasible given the nature of the evidence. RESULTS: We identified seven studies on early-life socio-economic circumstances, 10 studies on childhood obesity and six studies on early-life nutrition all relating to DNA methylation changes that met the stipulated inclusion criteria. The pool of evidence gathered, albeit small, favours a role of epigenetics and DNA methylation in biological embedding, but replication of findings, multiple comparison corrections, publication bias and causality are concerns remaining to be addressed in future investigations. CONCLUSIONS: Based on these results, we hypothesize that epigenetics, in particular DNA methylation, is a plausible mechanism through which early-life exposures are biologically embedded. This review describes the current status of the field and acts as a stepping stone for future, better designed investigations on how early-life exposures might become biologically embedded through epigenetic effects.

Low Y chromosome variation in Saudi-Arabian hamadryas baboons (Papio hamadryas hamadryas).

It is important to characterise the amount of variation on the mammalian Y chromosome in order to assess its potential for use in evolutionary studies. We report very low levels of polymorphism on the Y chromosome of Saudi-Arabian hamadryas baboons, Papio hamadryas hamadryas. We found no segregating sites on the Y, despite sequence analysis of 3 kb noncontiguous intron sequence in 16 males with divergent autosomal microsatellite genotypes, and a further analysis of 1.1 kb intron sequence in 97 males from four populations by SSCP. In addition, we tested seven human-derived Y-linked microsatellites in baboons. Only four of these loci were male-specific and only one was polymorphic in our 97 male sample set. Polymorphism on the Y chromosome of Arabian hamadryas appears to be low compared to other primate species for which data are available (eg humans, chimpanzees and bonobos). Low effective population size (Ne) of paternal genes due to polygyny and female-biased adult sex ratio is a potential reason for low Y chromosome variation in this species. However, low Ne for the Y should be counterbalanced to some extent by the species' atypical pattern of male philopatry and female-biased dispersal. Allelic richness averaged over seven loci was not significantly different between an African and an Arabian population, suggesting that loss of variation during the colonisation of Arabia does not explain low Y variation. Finally, in the absence of nucleotide polymorphism, it is unclear to what extent selection could be responsible for low Y variation in this species.

Bowel ischemia: a rare complication of thiopental treatment for status epilepticus.

BACKGROUND: Refractory status epilepticus (RSE) treatment is usually performed with coma induction using an appropriate general anesthetic. Most frequent complications are represented by hypotension and infection. Other side-effects may however be encountered. OBSERVATIONS: We describe two patients suffering from acute bowel ischemia after thiopental (THP) treatment for RSE. A 73-year-old man with a complex-patial RSE following an acute stroke received THP (303 mg/kg over 48 h); 36 h after THP discontinuation, he presented abdominal tenderness and lactate elevation. Necrosis of the terminal ileum and colon was seen during surgical exploration; he deceased shortly thereafter. A 21 year-old woman had a cryptogenic de novo generalized-convulsive RSE resistant to 5 attempts of EEG burst-suppression. During the 6th attempt, after THP (840 mg/kg over 150 h) together with mild hypothermia, she developed an ileus with elevated serum lactate; caecum necrosis was observed during surgery. Hypernatremia, acidosis and hyperlactatemia heralded this complication in both patients. CONCLUSION: In these two patients, mechanical vascular ischemia may have resulted from drug-induced paralytic ileus. To our knowledge, this is the first report describing this potential fatal side effect in adults with RSE.

History and Design of Iowa's Highway Maintenance and Weighing Facilities, 2003

In June 2001, the Iowa Department of Transportation announced the imminent closure and disposal of selected highway maintenance facilities as part of cost-cutting measures mandated by the Iowa legislature, an action that was to be completed by July 31, 2001. The DOT recognized that some of these facilities might be "historical sites," which in the Iowa Code are defined as any district, site, building or structure listed on the National Register of Historic Places or identified as eligible for listing in the National Register by the State Historic Preservation Office. Section 303 of the Code requires state agencies to "enter into an agreement with the Department of Cultural Affairs [in which the SHPO is located] to ensure the proper management, maintenance and development of historical sites." The DOT saw this disposal action as an opportunity to compile information about its highway maintenance facilities that could be employed in development of a management program for historic highway maintenance facilities in the future. Subsequently, the DOT authorized a similar study of highway weigh stations.

Nitrogen fertilization impact on agronomic traits of maize hybrids released at different decades

Genetic selection of maize hybrids is often conducted using high N rates during the breeding cycle. This procedure may either lead to the release of genotypes that present nitrogen luxury consumption or require a stronger N input to accomplish their yield potential. This work was carried out to evaluate the effects of N rates on grain yield and N use efficiency of hybrids cultivated in different decades in Southern Brazil. The trial was performed in Lages, Santa Catarina State. A split plot design was used. Hybrids Ag 12, Ag 28, Ag 303 and Ag 9012, released during the 60's, 70's, 80's and 90's, respectively, were evaluated in the main plots. Nitrogen rates equivalent to 0, 50, 100 and 200 kg ha-1 were side-dressed in the split-plots when each hybrid had six fully expanded leaves. Modern-day hybrid Ag 9012 had higher grain yield than hybrids of earlier eras, regardless of N rates. Under high doses of N, the older hybrids Ag 12 and Ag 28 took up more N and presented higher values of shoot dry matter at flowering than Ag 9012. Nonetheless, they set less grains per ear which contributed to decrease their grain yield and N use efficiency.

Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins.

Adrenoceptors are prototypic members of the superfamily of seven transmembrane domain, G protein-coupled receptors. Study of the properties of several mutationally activated adrenoceptors is deepening understanding of the normal functioning of this ubiquitous class of receptors. The new findings suggest an expansion of the classical ternary complex model of receptor action to include an explicit isomerization of the receptors from an inactive to an active state which couples to the G protein ('allosteric ternary complex model'). This isomerization involves conformational changes which may occur spontaneously, or be induced by agonists or appropriate mutations which abrogate the normal 'constraining' function of the receptor, allowing it to 'relax' into the active conformation. Robert Lefkowitz and colleagues discuss the physiological and pathophysiological implications of these new insights into regulation of receptor activity.

09002-001 Indian Springs Pond Watershed Final Report

Silver Creek is a warm water stream resource located in one of the most intensely cropped portions of Clayton County. The stream has been included on Iowa’s 303(d) list of impaired waters since 2002. Aquatic life, which should be present in Silver Creek, isn’t there. According to the Draft Total Maximum Daily Load (TMDL) for Silver Creek, the primary nonpoint pollution sources are soil erosion from agricultural land uses and direct deposition of ammonia by livestock with access to the stream. The Clayton Soil & Water Conservation District has begun efforts to remove Silver Creek from the impaired waters list. The District has promoted stream corridor and sinkhole protection, and the installation of buffer practices along Silver Creek and its tributaries. Conservation practices have been targeted to crop fields to reduce sediment delivery to the stream. A series of news articles, newsletters, and field days have been utilized to increase public understanding of water quality issues. Landowner interest has outweighed available cost share resources. Additional financial support will allow the project to build upon its early successes, to further address the identified impairments, and to respond to a long list of landowners that are interested in conservation work on their farms.

Essai sur les révolutions / par Arthur Bauer,...

Collection : Bibliothèque sociologique internationale ; 36

Streptococcus tigurinus is highly virulent in a rat model of experimental endocarditis.

Streptococcus tigurinus is responsible for systemic infections in humans including infective endocarditis. We investigated whether the invasive trait of S. tigurinus in humans correlated with an increased ability to induce IE in rats. Rats with catheter-induced aortic vegetations were inoculated with 10⁴ CFU/ml of either of four S. tigurinus strains AZ_3a(T), AZ_4a, AZ_8 and AZ_14, isolated from patients with infective endocarditis or with the well known IE pathogen Streptococcus gordonii (Challis). Aortic infection was assessed after 24 h. S. tigurinus AZ_3a(T), AZ_4a and AZ_14 produced endocarditis in ≥80% of rats whereas S. gordonii produced endocarditis in only 33% of animals (P<0.05). S. tigurinus AZ_8 caused vegetation infection in 56% of the animals. The capacity of S. tigurinus to induce aortic infection was not related to their ability to bind extracellular matrix proteins (fibrinogen, fibronectin or collagen) or to trigger platelet aggregation. However, all S. tigurinus isolates showed an enhanced resistance to phagocytosis by macrophages and two of them had an increased ability to enter endothelial cells, key attributes of invasive streptococcal species.

Israel Scheffler - pragmatisti, realisti vai relativisti?

S. 303: Timo Tolska vastaa / Timo Tolska