Mitochondrial mislocalization and altered assembly of a cluster of Barth syndrome mutant tafazzins

None of the 28 identified point mutations in tafazzin (Taz1p), which is the mutant gene product associated with Barth syndrome (BTHS), has a biochemical explanation. In this study, endogenous Taz1p was localized to mitochondria in association with both the inner and outer mitochondrial membranes facing the intermembrane space (IMS). Unexpectedly, Taz1p does not contain transmembrane (TM) segments. Instead, Taz1p membrane association involves a segment that integrates into, but not through, the membrane bilayer. Residues 215–232, which were predicted to be a TM domain, were identified as the interfacial membrane anchor by modeling four distinct BTHS mutations that occur at conserved residues within this segment. Each Taz1p mutant exhibits altered membrane association and is nonfunctional. However, the basis for Taz1p dysfunction falls into the following two categories: (1) mistargeting to the mitochondrial matrix or (2) correct localization associated with aberrant complex assembly. Thus, BTHS can be caused by mutations that alter Taz1p sorting and assembly within the mitochondrion, indicating that the lipid target of Taz1p is resident to IMS-facing leaflets

Entrainment of the Melatonin Rhythms in Early Postnatal Lambs and Their Mothers

Although the developing sheep can produce an appropriately timed melatonin rhythm as early as 1 week after birth, it is not known whether the lamb is able to adjust its melatonin rhythm to a change in daylength. The ability of the young lamb to entrain its pattern of melatonin secretion to a new photoperiod was determined in the present study. Eight female lambs and their mothers were raised in long days (LD 16:8) beginning 2 weeks post partum. At 7 weeks of age, the time of lights-off was advanced 8 hr, the short-day photoperiod then being LD 8:16; the time of lights-on remained unchanged. Concentrations of melatonin were measured in blood samples collected hourly on days - 1, 0, 2, 4, 6, and 13 relative to the light change. On day 0, all mothers and daughters had advanced the onset of melatonin secretion by at least 1 hr, and by day 13, 12 of 16 had completely entrained to the new photoperiod. The rate of entrainment among individuals varied; the mean rate for lambs and mothers did not differ. This study provides evidence that the melatonin-rhythm-generating system matures shortly after birth.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68290/2/10.1177_074873048900400405.pd

Modeling sulfate reduction in methane hydrate-bearing continental margin sediments : does a sulfate-methane transition require anaerobic oxidation of methane?

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 12 (2011): Q07006, doi:10.1029/2011GC003501.The sulfate-methane transition (SMT), a biogeochemical zone where sulfate and methane are metabolized, is commonly observed at shallow depths (1–30 mbsf) in methane-bearing marine sediments. Two processes consume sulfate at and above the SMT, anaerobic oxidation of methane (AOM) and organoclastic sulfate reduction (OSR). Differentiating the relative contribution of each process is critical to estimate methane flux into the SMT, which, in turn, is necessary to predict deeper occurrences of gas hydrates in continental margin sediments. To evaluate the relative importance of these two sulfate reduction pathways, we developed a diagenetic model to compute the pore water concentrations of sulfate, methane, and dissolved inorganic carbon (DIC). By separately tracking DIC containing 12C and 13C, the model also computes δ13C-DIC values. The model reproduces common observations from methane-rich sediments: a well-defined SMT with no methane above and no sulfate below and a δ13C-DIC minimum at the SMT. The model also highlights the role of upward diffusing 13C-enriched DIC in contributing to the carbon isotope mass balance of DIC. A combination of OSR and AOM, each consuming similar amounts of sulfate, matches observations from Site U1325 (Integrated Ocean Drilling Program Expedition 311, northern Cascadia margin). Without AOM, methane diffuses above the SMT, which contradicts existing field data. The modeling results are generalized with a dimensional analysis to the range of SMT depths and sedimentation rates typical of continental margins. The modeling shows that AOM must be active to establish an SMT wherein methane is quantitatively consumed and the δ13C-DIC minimum occurs. The presence of an SMT generally requires active AOM

Building cloud applications for challenged networks

Cloud computing has seen vast advancements and uptake in many parts of the world. However, many of the design patterns and deployment models are not very suitable for locations with challenged networks such as countries with no nearby datacenters. This paper describes the problem and discusses the options available for such locations, focusing specifically on community clouds as a short-term solution. The paper highlights the impact of recent trends in the development of cloud applications and how changing these could better help deployment in challenged networks. The paper also outlines the consequent challenges in bridging different cloud deployments, also known as cross-cloud computing

The Chicken Yolk Sac IgY Receptor, a Mammalian Mannose Receptor Family Member, Transcytoses IgY across Polarized Epithelial Cells

In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds

A demonstration of an affinity between pyrite and organic matter in a hydrothermal setting

One of the key-principles of the iron-sulphur world theory is to bring organic molecules close enough to interact with each other, using the surface of pyrite as a substrate in a hydrothermal setting. The present paper explores the relationship of pyrite and organic matter in a hydrothermal setting from the geological record; in hydrothermal calcite veins from Carboniferous limestones in central Ireland. Here, the organic matter is accumulated as coatings around, and through, pyrite grains. Most of the pyrite grains are euhedral-subhedral crystals, ranging in size from ca 0.1-0.5 mm in diameter, and they are scattered throughout the matrix of the vein calcite. The organic matter was deposited from a hydrothermal fluid at a temperature of at least 200°C, and gives a Raman signature of disordered carbon. This study points to an example from a hydrothermal setting in the geological record, demonstrating that pyrite can have a high potential for the concentration and accumulation of organic materials

Metalloprotease OMA1 Fine-tunes Mitochondrial Bioenergetic Function and Respiratory Supercomplex Stability

Mitochondria are involved in key cellular functions including energy production, metabolic homeostasis, and apoptosis. Normal mitochondrial function is preserved by several interrelated mechanisms. One mechanism – intramitochondrial quality control (IMQC) – is represented by conserved proteases distributed across mitochondrial compartments. Many aspects and physiological roles of IMQC components remain unclear. Here, we show that the IMQC protease Oma1 is required for the stability of the respiratory supercomplexes and thus balanced and tunable bioenergetic function. Loss of Oma1 activity leads to a specific destabilization of respiratory supercomplexes and consequently to unbalanced respiration and progressive respiratory decline in yeast. Similarly, experiments in cultured Oma1-deficient mouse embryonic fibroblasts link together impeded supercomplex stability and inability to maintain proper respiration under conditions that require maximal bioenergetic output. Finally, transient knockdown of OMA1 in zebrafish leads to impeded bioenergetics and morphological defects of the heart and eyes. Together, our biochemical and genetic studies in yeast, zebrafish and mammalian cells identify a novel and conserved physiological role for Oma1 protease in fine-tuning of respiratory function. We suggest that this unexpected physiological role is important for cellular bioenergetic plasticity and may contribute to Oma1- associated disease phenotypes in humans

Long term geological record of a global deep subsurface microbial habitat in sand injection complexes

Peer reviewedPublisher PD

Active mud volcanoes on the continental slope of the Canadian Beaufort Sea

The major geochemical characteristics of Red Sea brine are summarized for 11 brine-filled deeps located along the central graben axis between 19°N and 27°N. The major element composition of the different brine pools is mainly controlled by variable mixing situations of halite-saturated solution (evaporite dissolution) with Red Sea deep water. The brine chemistry is also influenced by hydrothermal water/rock interaction, whereas magmatic and sedimentary rock reactions can be distinguished by boron, lithium, and magnesium/calcium chemistry. Moreover, hydrocarbon chemistry (concentrations and δ 13 C data) of brine indicates variable injection of light hydrocarbons from organic source rocks and strong secondary (bacterial or thermogenic) degradation processes. A simple statistical cluster analysis approach was selected to look for similarities in brine chemistry and to classify the various brine pools, as the measured chemical brine compositions show remarkably strong concentration variations for some elements. The cluster analysis indicates two main classes of brine. Type I brine chemistry (Oceanographer and Kebrit Deeps) is controlled by evaporite dissolution and contributions from sediment alteration. The Type II brine (Suakin, Port Sudan, Erba, Albatross, Discovery, Atlantis II, Nereus, Shaban, and Conrad Deeps) is influenced by variable contributions from volcanic/ magmatic rock alteration. The chemical brine classification can be correlated with the sedimentary and tectonic setting of the related depressions. Type I brine-filled deeps are located slightly off-axis from the central Red Sea graben. A typical " collapse structure formation " which has been defined for the Kebrit Deep by evaluating seismic and geomorphological data probably corresponds to our Type I brine. Type II brine located in depressions in the northern Red Sea (i.e., Conrad and Shaban Deeps) could be correlated to " volcanic intrusion-/extrusion-related " deep formation. The chemical indications for hydrothermal influence on Conrad and Shaban Deep brine can be related to brines from the multi-deeps region in the central Red Sea, where volcanic/magmatic fluid/rock interaction is most obvious. The strongest hydrothermal influence is observed in Atlantis II brine (central multi-deeps region), which is also the hottest Red Sea brine body in 2011 (*68.2 °C)