Young off-axis volcanism along the ultraslow-spreading Southwest Indian Ridge

Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 3 (2010): 286-292, doi:10.1038/ngeo824.Mid-ocean ridge crustal accretion occurs continuously at all spreading rates through a combination of magmatic and tectonic processes. Fast to slow spreading ridges are largely built by adding magma to narrowly focused neovolcanic zones. In contrast, ultraslow spreading ridge construction significantly relies on tectonic accretion, which is characterized by thin volcanic crust, emplacement of mantle peridotite directly to the seafloor, and unique seafloor fabrics with variable segmentation patterns. While advances in remote imaging have enhanced our observational understanding of crustal accretion at all spreading rates, temporal information is required in order to quantitatively understand mid-ocean ridge construction. However, temporal information does not exist for ultraslow spreading environments. Here, we utilize U-series eruption ages to investigate crustal accretion at an ultraslow spreading ridge for the first time. Unexpectedly young eruption ages throughout the Southwest Indian ridge rift valley indicate that neovolcanic activity is not confined to the spreading axis, and that magmatic crustal accretion occurs over a wider zone than at faster spreading ridges. These observations not only suggest that crustal accretion at ultraslow spreading ridges is distinct from faster spreading ridges, but also that the magma transport mechanisms may differ as a function of spreading rate.This work was supported by the following NSF grants: NSF-OCE 0137325; NSF-OCE 060383800; and NSF-OCE 062705300

The SOS Pilot Study: a RCT of routine oxygen supplementation early after acute stroke—effect on recovery of neurological function at one week

Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke

Identification of monetary policy in SVAR models: A data-oriented perspective

In the literature using short-run timing restrictions to identify monetary policy shocks in vector-auto-regressions (VAR) there is a debate on whether (i) contemporaneous real activity and prices or (ii) only data typically observed with high frequency should be assumed to be in the information set of the central bank when the interest rate decision is taken. This paper applies graphical modeling theory, a data-based tool, in a small-scale VAR of the US economy to shed light on this issue. Results corroborate the second type of assumption

Effect of bilirubin on cytochrome c oxidase activity of mitochondria from mouse brain and liver

<p>Abstract</p> <p>Background</p> <p>The unbound, free concentration (B_f) of unconjugated bilirubin (UCB), and not the total UCB level, has been shown to correlate with bilirubin cytotoxicity, but the key molecular mechanisms accounting for the toxic effects of UCB are largely unknown.</p> <p>Findings</p> <p>Mouse liver mitochondria increase unbound UCB oxidation, consequently increasing the apparent rate constant for unbound UCB oxidation by HRP (Kp), higher than in control and mouse brain mitochondria, emphasizing the importance of determining Kp in complete systems containing the organelles being studied. The <it>in vitro </it>effects of UCB on cytochrome <it>c </it>oxidase activity in mitochondria isolated from mouse brain and liver were studied at B_franging from 22 to 150 nM. The results show that UCB at B_fup to 60 nM did not alter mitochondrial cytochrome <it>c </it>oxidase activity, while the higher concentrations significantly inhibited the enzyme activity by 20% in both liver and brain mitochondria.</p> <p>Conclusions</p> <p>We conclude that it is essential to include the organelles being studied in the medium used in measuring both Kp and B_f. A moderately elevated, pathophysiologically-relevant B_fimpaired the cytochrome <it>c </it>oxidase activity modestly in mitochondria from mouse brain and liver.</p

Congenital Sensorineural Deafness in Australian Stumpy-Tail Cattle Dogs Is an Autosomal Recessive Trait That Maps to CFA10

Congenital sensorineural deafness is an inherited condition found in many dog breeds, including Australian Stumpy-tail Cattle Dogs (ASCD). This deafness is evident in young pups and may affect one ear (unilateral) or both ears (bilateral). The genetic locus/loci involved is unknown for all dog breeds. The aims of this study were to determine incidence, inheritance mechanism, and possible association of congenital sensorineural deafness with coat colour in ASCD and to identify the genetic locus underpinning this disease.A total of 315 ASCD were tested for sensorineural deafness using the brain stem auditory evoked response (BAER) test. Disease penetrance was estimated directly, using the ratio of unilaterally to bilaterally deaf dogs, and segregation analysis was performed using Mendel. A complete genome screen was undertaken using 325 microsatellites spread throughout the genome, on a pedigree of 50 BAER tested ASCD in which deafness was segregating. Fifty-six dogs (17.8%) were deaf, with 17 bilaterally and 39 unilaterally deaf. Unilaterally deaf dogs showed no significant left/right bias (p = 0.19) and no significant difference was observed in frequencies between the sexes (p = 0.18). Penetrance of deafness was estimated as 0.72. Testing the association of red/blue coat colour and deafness without accounting for pedigree structure showed that red dogs were 1.8 times more likely to be deaf (p = 0.045). The within family association between red/blue coat colour and deafness was strongly significant (p = 0.00036), with red coat colour segregating more frequently with deafness (COR = 0.48). The relationship between deafness and coat speckling approached significance (p = 0.07), with the lack of statistical significance possibly due to only four families co-segregating for both deafness and speckling. The deafness phenotype was mapped to CFA10 (maximum linkage peak on CFA10 -log10 p-value = 3.64), as was both coat colour and speckling. Fine mapping was then performed on 45 of these 50 dogs and a further 48 dogs (n = 93). Sequencing candidate gene Sox10 in 6 hearing ASCD, 2 unilaterally deaf ASCD and 2 bilaterally deaf ASCD did not reveal any disease-associated mutations.Deafness in ASCD is an incompletely penetrant autosomal recessive inherited disease that maps to CFA10

Investigation of Mitochondrial Dysfunction by Sequential Microplate-Based Respiration Measurements from Intact and Permeabilized Neurons

Mitochondrial dysfunction is a component of many neurodegenerative conditions. Measurement of oxygen consumption from intact neurons enables evaluation of mitochondrial bioenergetics under conditions that are more physiologically realistic compared to isolated mitochondria. However, mechanistic analysis of mitochondrial function in cells is complicated by changing energy demands and lack of substrate control. Here we describe a technique for sequentially measuring respiration from intact and saponin-permeabilized cortical neurons on single microplates. This technique allows control of substrates to individual electron transport chain complexes following permeabilization, as well as side-by-side comparisons to intact cells. To illustrate the utility of the technique, we demonstrate that inhibition of respiration by the drug KB-R7943 in intact neurons is relieved by delivery of the complex II substrate succinate, but not by complex I substrates, via acute saponin permeabilization. In contrast, methyl succinate, a putative cell permeable complex II substrate, failed to rescue respiration in intact neurons and was a poor complex II substrate in permeabilized cells. Sequential measurements of intact and permeabilized cell respiration should be particularly useful for evaluating indirect mitochondrial toxicity due to drugs or cellular signaling events which cannot be readily studied using isolated mitochondria

The perceived impact of location privacy: A web-based survey of public health perspectives and requirements in the UK and Canada

<p>Abstract</p> <p>Background</p> <p>The "place-consciousness" of public health professionals is on the rise as spatial analyses and Geographic Information Systems (GIS) are rapidly becoming key components of their toolbox. However, "place" is most useful at its most precise, granular scale – which increases identification risks, thereby clashing with privacy issues. This paper describes the views and requirements of public health professionals in Canada and the UK on privacy issues and spatial data, as collected through a web-based survey.</p> <p>Methods</p> <p>Perceptions on the impact of privacy were collected through a web-based survey administered between November 2006 and January 2007. The survey targeted government, non-government and academic GIS labs and research groups involved in public health, as well as public health units (Canada), ministries, and observatories (UK). Potential participants were invited to participate through personally addressed, standardised emails.</p> <p>Results</p> <p>Of 112 invitees in Canada and 75 in the UK, 66 and 28 participated in the survey, respectively. The completion proportion for Canada was 91%, and 86% for the UK. No response differences were observed between the two countries. Ninety three percent of participants indicated a requirement for personally identifiable data (PID) in their public health activities, including geographic information. Privacy was identified as an obstacle to public health practice by 71% of respondents. The overall self-rated median score for knowledge of privacy legislation and policies was 7 out of 10. Those who rated their knowledge of privacy as high (at the median or above) also rated it significantly more severe as an obstacle to research (<it>P </it>< 0.001). The most critical cause cited by participants in both countries was bureaucracy.</p> <p>Conclusion</p> <p>The clash between PID requirements – including granular geography – and limitations imposed by privacy and its associated bureaucracy require immediate attention and solutions, particularly given the increasing utilisation of GIS in public health. Solutions include harmonization of privacy legislation with public health requirements, bureaucratic simplification, increased multidisciplinary discourse, education, and development of toolsets, algorithms and guidelines for using and reporting on disaggregate data.</p

Multi-Patterned Dynamics of Mitochondrial Fission and Fusion in a Living Cell

Mitochondria are highly-dynamic organelles, but it is challenging to monitor quantitatively their dynamics in a living cell. Here we developed a novel approach to determine the global occurrence of mitochondrial fission and fusion events in living human epithelial cells (Hela) and mouse embryonic fibroblast cells (MEF). Distinct patterns of sequential events including fusion followed by fission (Fu-Fi), the so-called “kiss and run” model previously described, fission followed by fusion (Fi-Fu), fusion followed by fusion (Fu-Fu), and fission followed by fission (Fi-Fi) were observed concurrently. The paired events appeared in high frequencies with short lifetimes and large sizes of individual mitochondria, as compared to those for unpaired events. The high frequencies of paired events were found to be biologically significant. The presence of membrane uncoupler CCCP enhanced the frequency of paired events (from both Fu-Fi and Fi-Fu patterns) with a reduced mitochondrial size. Knock-out of mitofusin protein Mfn1 increased the frequency of fission with increased lifetime of unpaired events whereas deletion of both Mfn1 and Mfn2 resulted in an instable dynamics. These results indicated that the paired events were dominant but unpaired events were not negligible, which provided a new insight into mitochondrial dynamics. In addition to kiss and run model of action, our data suggest that, from a global visualization over an entire cell, multiple patterns of action appeared in mitochondrial fusion and fission

Regional mitochondrial DNA and cell-type changes in post-mortem brains of non-diabetic Alzheimer’s disease are not present in diabetic Alzheimer’s disease

Background: Mitochondrial dysfunction is implicated in both diabetes and Alzheimer’s disease (AD), and diabetes also increases the risk of AD, however the combined impact of AD and diabetes on brain mitochondria is unknown. The purpose of this study was to test the hypothesis that the combination of both diabetes and AD exacerbates mitochondrial dysfunction. Methods: Post-mortem human brains (n=74), were used to determine mitochondrial DNA (mtDNA) content of cerebellum, frontal cortex and parietal cortex by quantifying absolute mtDNA copy number/cell using real time qPCR. mtDNA content was compared between diabetic and non-diabetic cases representing non-cognitively impaired controls (NCI), mildly cognitively impaired (MCI) and AD. A subset of parietal cortex samples was used to quantify mRNAs corresponding to cell types and mitochondrial function. Immune-staining of parietal cortex sections followed by semi-automated stereological assessment was performed to assess cell types. Results. Using mtDNA as an indicator of mitochondrial content, we observed significant regional variation, being highest in the parietal cortex, and lowest in the cerebellum. In the absence of diabetes, AD cases had decreased parietal cortex mtDNA, reduced MAP2 (neuronal) mRNA and increased GFAP (astrocyte) mRNA, relative to NCI. However, in the presence of both diabetes and AD, we did not observe these changes in the parietal cortex. Irrespective of cognitive status, all 3 brain regions in diabetic cases had significantly higher mtDNA than the non-diabetic cases. Conclusion. Our data show that the parietal cortex has the highest mitochondrial content but is also the most vulnerable to changes in AD, as shown by reduced mtDNA and neurones in this region. In contrast, when patients have both diabetes and AD, the AD associated parietal cortex changes are no longer seen, suggesting that the pathology observed in diabetic AD may be different to that seen in non-diabetic AD. The lack of clear functional changes in mitochondrial parameters in diabetic AD suggest that there may be different mechanisms contributing to cognitive impairment in diabetes and their impact on the respective disease neuro-pathologies remain to be fully understood

Selective Enrichment and Sequencing of Whole Mitochondrial Genomes in the Presence of Nuclear Encoded Mitochondrial Pseudogenes (Numts)

Numts are an integral component of many eukaryote genomes offering a snapshot of the evolutionary process that led from the incorporation of an α-proteobacterium into a larger eukaryotic cell some 1.8 billion years ago. Although numt sequence can be harnessed as molecular marker, these sequences often remain unidentified and are mistaken for genuine mtDNA leading to erroneous interpretation of mtDNA data sets. It is therefore indispensable that during the process of amplifying and sequencing mitochondrial genes, preventive measures are taken to ensure the exclusion of numts to guarantee the recovery of genuine mtDNA. This applies to mtDNA analyses in general but especially to studies where mtDNAs are sequenced de novo as the launch pad for subsequent mtDNA-based research. By using a combination of dilution series and nested rolling circle amplification (RCA), we present a novel strategy to selectively amplify mtDNA and exclude the amplification of numt sequence. We have successfully applied this strategy to de novo sequence the mtDNA of the Black Field Cricket Teleogryllus commodus, a species known to contain numts. Aligning our assembled sequence to the reference genome of Teleogryllus emma (GenBank EU557269.1) led to the identification of a numt sequence in the reference sequence. This unexpected result further highlights the need of a reliable and accessible strategy to eliminate this source of error