Mitochondria and the regulation of free radical damage in the eye

Neuronal cell death can be determined by the overall level of reactive oxygen species (ROS) resulting from the combination of extrinsic sources and intrinsic production as a byproduct of oxidative phosphorylation. Key controllers of the intrinsic production of ROS are the mitochondrial uncoupling proteins (UCPs). By allowing a controlled leak of protons across the inner mitochondrial membrane activation of these proteins can decrease ROS and promote cell survival. In both primate models of Parkinson’s disease and mouse models of seizures, increased activity of UCP2 significantly increased neuronal cells survival. In the retina UCP2 is expressed in many neurons and glial cells, but was not detected in rod photoreceptors. Retinal ganglion cell survival following excitotoxic damage was much greater in animals overexpressing UCP2. Traditional Chinese medicines, such as an extract of Cistanche tubulosa, may provide benefit by altering mitochondrial metabolism

Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.

New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved

Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin

C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.C content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5–15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014). Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1–5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively), less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05), and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05) than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation.C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age

Genetic Predisposition for Type 2 Diabetes, but Not for Overweight/Obesity, Is Associated with a Restricted Adipogenesis

BACKGROUND: Development of Type 2 diabetes, like obesity, is promoted by a genetic predisposition. Although several genetic variants have been identified they only account for a small proportion of risk. We have asked if genetic risk is associated with abnormalities in storing excess lipids in the abdominal subcutaneous adipose tissue. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 164 lean and 500 overweight/obese individuals with or without a genetic predisposition for Type 2 diabetes or obesity. Adipose cell size was measured in biopsies from the abdominal adipose tissue as well as insulin sensitivity (HOMA index), HDL-cholesterol and Apo AI and Apo B. 166 additional non-obese individuals with a genetic predisposition for Type 2 diabetes underwent a euglycemic hyperinsulinemic clamp to measure insulin sensitivity. Genetic predisposition for Type 2 diabetes, but not for overweight/obesity, was associated with inappropriate expansion of the adipose cells, reduced insulin sensitivity and a more proatherogenic lipid profile in non-obese individuals. However, obesity per se induced a similar expansion of adipose cells and dysmetabolic state irrespective of genetic predisposition. CONCLUSIONS/SIGNIFICANCE: Genetic predisposition for Type 2 diabetes, but not obesity, is associated with an impaired ability to recruit new adipose cells to store excess lipids in the subcutaneous adipose tissue, thereby promoting ectopic lipid deposition. This becomes particularly evident in non-obese individuals since obesity per se promotes a dysmetabolic state irrespective of genetic predisposition. These results identify a novel susceptibility factor making individuals with a genetic predisposition for Type 2 diabetes particularly sensitive to the environment and caloric excess

Modeling Activity and Target-Dependent Developmental Cell Death of Mouse Retinal Ganglion Cells Ex Vivo

Programmed cell death is widespread during the development of the central nervous system and serves multiple purposes including the establishment of neural connections. In the mouse retina a substantial reduction of retinal ganglion cells (RGCs) occurs during the first postnatal week, coinciding with the formation of retinotopic maps in the superior colliculus (SC). We previously established a retino-collicular culture preparation which recapitulates the progressive topographic ordering of RGC projections during early post-natal life. Here, we questioned whether this model could also be suitable to examine the mechanisms underlying developmental cell death of RGCs. Brn3a was used as a marker of the RGCs. A developmental decline in the number of Brn3a-immunolabelled neurons was found in the retinal explant with a timing that paralleled that observed in vivo. In contrast, the density of photoreceptors or of starburst amacrine cells increased, mimicking the evolution of these cell populations in vivo. Blockade of neural activity with tetrodotoxin increased the number of surviving Brn3a-labelled neurons in the retinal explant, as did the increase in target availability when one retinal explant was confronted with 2 or 4 collicular slices. Thus, this ex vivo model reproduces the developmental reduction of RGCs and recapitulates its regulation by neural activity and target availability. It therefore offers a simple way to analyze developmental cell death in this classic system. Using this model, we show that ephrin-A signaling does not participate to the regulation of the Brn3a population size in the retina, indicating that eprhin-A-mediated elimination of exuberant projections does not involve developmental cell death

Ecosystem development after mangrove wetland creation : plant–soil change across a 20-year chronosequence

This paper is not subject to U.S. copyright. The definitive version was published in Ecosystems 15 (2012): 848-866, doi:10.1007/s10021-012-9551-1.Mangrove wetland restoration and creation efforts are increasingly proposed as mechanisms to compensate for mangrove wetland losses. However, ecosystem development and functional equivalence in restored and created mangrove wetlands are poorly understood. We compared a 20-year chronosequence of created tidal wetland sites in Tampa Bay, Florida (USA) to natural reference mangrove wetlands. Across the chronosequence, our sites represent the succession from salt marsh to mangrove forest communities. Our results identify important soil and plant structural differences between the created and natural reference wetland sites; however, they also depict a positive developmental trajectory for the created wetland sites that reflects tightly coupled plant-soil development. Because upland soils and/or dredge spoils were used to create the new mangrove habitats, the soils at younger created sites and at lower depths (10–30 cm) had higher bulk densities, higher sand content, lower soil organic matter (SOM), lower total carbon (TC), and lower total nitrogen (TN) than did natural reference wetland soils. However, in the upper soil layer (0–10 cm), SOM, TC, and TN increased with created wetland site age simultaneously with mangrove forest growth. The rate of created wetland soil C accumulation was comparable to literature values for natural mangrove wetlands. Notably, the time to equivalence for the upper soil layer of created mangrove wetlands appears to be faster than for many other wetland ecosystem types. Collectively, our findings characterize the rate and trajectory of above- and below-ground changes associated with ecosystem development in created mangrove wetlands; this is valuable information for environmental managers planning to sustain existing mangrove wetlands or mitigate for mangrove wetland losses

Postpyloric enteral nutrition in the critically ill child with shock: a prospective observational study

<p>Abstract</p> <p>Background</p> <p>Tolerance to enteral nutrition in the critically ill child with shock has not been studied. The purpose of the study was to analyze the characteristics of enteral nutrition and its tolerance in the critically ill child with shock and to compare this with non-shocked patients.</p> <p>Methods</p> <p>A prospective, observational study was performed including critically ill children with shock who received postpyloric enteral nutrition (PEN). The type of nutrition used, its duration, tolerance, and gastrointestinal complications were assessed. The 65 children with shock who received PEN were compared with 461 non-shocked critically ill children who received PEN.</p> <p>Results</p> <p>Sixty-five critically ill children with shock, aged between 21 days and 22 years, received PEN. 75.4% of patients with shock received PEN exclusively. The mean duration of the PEN was 25.2 days and the maximum calorie intake was 79.4 kcal/kg/day. Twenty patients with shock (30.7%) presented gastrointestinal complications, 10 (15.4%) abdominal distension and/or excessive gastric residue, 13 (20%) diarrhoea, 1 necrotising enterocolitis, and 1 duodenal perforation due to the postpyloric tube. The frequency of gastrointestinal complications was significantly higher than in the other 461 critically ill children (9.1%). PEN was suspended due to gastrointestinal complications in 6 patients with shock (9.2%). There were 18 deaths among the patients with shock and PEN (27.7%). In only one patient was the death related to complications of the nutrition.</p> <p>Conclusion</p> <p>Although most critically ill children with shock can tolerate postpyloric enteral nutrition, the incidence of gastrointestinal complications is higher in this group of patients than in other critically ill children.</p

Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF

If the Technicolor omega_T particle exists, a likely decay mode is omega_T -> gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab Tevatron for events with a photon and two jets, where one of the jets must contain a secondary vertex implying the presence of a b quark. We find no excess of events above standard model expectations. We express the result of an exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs): http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps FERMILAB-PUB-98/321-

Measurement of the B0 anti-B0 oscillation frequency using l- D*+ pairs and lepton flavor tags

The oscillation frequency Delta-md of B0 anti-B0 mixing is measured using the partially reconstructed semileptonic decay anti-B0 -> l- nubar D*+ X. The data sample was collected with the CDF detector at the Fermilab Tevatron collider during 1992 - 1995 by triggering on the existence of two lepton candidates in an event, and corresponds to about 110 pb-1 of pbar p collisions at sqrt(s) = 1.8 TeV. We estimate the proper decay time of the anti-B0 meson from the measured decay length and reconstructed momentum of the l- D*+ system. The charge of the lepton in the final state identifies the flavor of the anti-B0 meson at its decay. The second lepton in the event is used to infer the flavor of the anti-B0 meson at production. We measure the oscillation frequency to be Delta-md = 0.516 +/- 0.099 +0.029 -0.035 ps-1, where the first uncertainty is statistical and the second is systematic.Comment: 30 pages, 7 figures. Submitted to Physical Review

Search for New Particles Decaying to top-antitop in proton-antiproton collisions at squareroot(s)=1.8 TeV

We use 106 \ipb of data collected with the Collider Detector at Fermilab to search for narrow-width, vector particles decaying to a top and an anti-top quark. Model independent upper limits on the cross section for narrow, vector resonances decaying to \ttbar are presented. At the 95% confidence level, we exclude the existence of a leptophobic \zpr boson in a model of topcolor-assisted technicolor with mass M_{\zpr} $<$ 480 \gev for natural width $\Gamma$ = 0.012 M_{\zpr}, and M_{\zpr} $<$ 780 \gev for $\Gamma$ = 0.04 M_{\zpr}.Comment: The CDF Collaboration, submitted to PRL 25-Feb-200