Continental Arc and Back-Arc Migration in Eastern NE China: New Constraints on Cretaceous Paleo-Pacific Subduction and Rollback

Tectonic evolution models for the Cretaceous Russia Sikhote-Alin and eastern NE China continental margin and interior remain controversial. To understand the magmatic evolution over time and assess regional geodynamic processes, we sampled a diverse array of igneous rocks and employed zircon U-Pb dating, hornblende and plagioclase 40Ar-39Ar dating, whole-rock major and trace element analysis, and 87Sr/86Sr and 143Nd/144Nd isotopic analysis. The west Sikhote-Alin Pikeshan Formation volcanics and associated granites occurred at a peak of ~118 Ma and are hosted by the Triassic-Jurassic accretionary complex. Their whole rock geochemistry shows that SiO2 increased in a linear trend, Eu/Eu* values decreased from 0.91 to 0.38, and eNd(t) values decreased from +0.6 to -2.9, indicating magma mixing of a juvenile mantle wedge source and continental crust, consistent with a continental arc. The arc thickened over time with a felsic dike hosted in the Pikeshan granites showing depletion in heavy rare earth elements. The termination of the arc front is documented by the ~107-Ma intermediate lamprophyre and felsic dikes with eNd(t) values of +4.5 to +1.1, indicating an increased mantle contribution over time. Lithospheric extension of the Jiamusi Block to the west occurred at ~100 Ma, characterized by bimodal volcanism and composite dike emplacement, suggestive of asthenosphere upwelling. Based on the spatial and temporal distribution of these igneous rocks, the continental arc and intraplate magmatism migrated eastward contemporaneously. We favor a model invoking rollback of the subducting Paleo-Pacific slab affecting a long-lived continental arc

Expression of monolysocardiolipin acyltransferase activity is regulated in concert with the level of cardiolipin and cardiolipin biosynthesis in the mammalian heart

BACKGROUND: Monolysocardiolipin acyltransferase (MLCL AT) catalyzes the acylation of monolysocardiolipin to cardiolipin in mammalian tissues. We previously reported that cardiac cardiolipin levels, MLCL AT and cardiolipin synthase activities were all elevated in rats made hyperthyroid by thyroxine treatment. In this study, we examined if cardiac mitochondrial MLCL AT activity was dependent upon the biosynthesis and level of cardiolipin in the heart. Rat heart mitochondrial MLCL AT activity was determined under conditions in which the levels of cardiac cardiolipin and cardiolipin synthase activity were either reduced or unaltered using four different disease models in the rat. In addition, these parameters were examined in a murine model of cardiac cell differentiation. RESULTS: In rats made hypothyroid by treatment with 6-n-propyl-2-thiouracil in the drinking water for 34 days, cardiac cardiolipin content was decreased 29% (p < 0.025) and this was associated with a 32% decrease (p < 0.025) in cardiolipin synthase and a 35% reduction (p < 0.025) in MLCL AT activities. Streptozotocin-induced diabetes or hyperinsulinemia in rats did not affect cardiac cardiolipin content nor MLCL AT and cardiolipin synthase activities. Finally, cardiolipin content, MLCL AT and cardiolipin synthase activities were unaltered during murine P19 teratocarcinoma cell differentiation into cardiac myocytes. In all models, phospholipase A(2) activities were unaltered compared with controls. CONCLUSION: We propose a general model in which the expression of MLCL AT activity is regulated in concert with the biosynthesis and level of cardiolipin in the heart

The dynamics of cardiolipin synthesis post-mitochondrial fusion

AbstractAlteration in mitochondrial fusion may regulate mitochondrial metabolism. Since the phospholipid cardiolipin (CL) is required for function of the mitochondrial respiratory chain, we examined the dynamics of CL synthesis in growing Hela cells immediately after and 12h post-fusion. Cells were transiently transfected with Mfn-2, to promote fusion, or Mfn-2 expressing an inactive GTPase for 24h and de novo CL biosynthesis was examined immediately after or 12h post-fusion. Western blot analysis confirmed elevated Mfn-2 expression and electron microscopic analysis revealed that Hela cell mitochondrial structure was normal immediately after and 12h post-fusion. Cells expressing Mfn-2 exhibited reduced CL de novo biosynthesis from [1,3-3H]glycerol immediately after fusion and this was due to a decrease in phosphatidylglycerol phosphate synthase (PGPS) activity and its mRNA expression. In contrast, 12h post-mitochondrial fusion cells expressing Mfn-2 exhibited increased CL de novo biosynthesis from [1,3-3H]glycerol and this was due to an increase in PGPS activity and its mRNA expression. Cells expressing Mfn-2 with an inactive GTPase activity did not exhibit alterations in CL de novo biosynthesis immediately after or 12h post-fusion. The Mfn-2 mediated alterations in CL de novo biosynthesis were not accompanied by alterations in CL or monolysoCL mass. [1-14C]Oleate incorporation into CL was elevated at 12h post-fusion indicating increased CL resynthesis. The reason for the increased CL resynthesis was an increased mRNA expression of tafazzin, a mitochondrial CL resynthesis enzyme. Ceramide-induced expression of PGPS in Hela cells or in CHO cells did not alter expression of Mfn-2 indicating that Mfn-2 expression is independent of altered CL synthesis mediated by elevated PGPS. In addition, Mfn-2 expression was not altered in Hela cells expressing phospholipid scramblase-3 or a disrupted scramblase indicating that proper CL localization within mitochondria is not essential for Mfn-2 expression. The results suggest that immediately post-mitochondrial fusion CL de novo biosynthesis is “slowed down” and then 12h post-fusion it is “upregulated”. The implications of this are discussed

Alternative Splicing Events Identified in Human Embryonic Stem Cells and Neural Progenitors

Human embryonic stem cells (hESCs) and neural progenitor (NP) cells are excellent models for recapitulating early neuronal development in vitro, and are key to establishing strategies for the treatment of degenerative disorders. While much effort had been undertaken to analyze transcriptional and epigenetic differences during the transition of hESC to NP, very little work has been performed to understand post-transcriptional changes during neuronal differentiation. Alternative RNA splicing (AS), a major form of post-transcriptional gene regulation, is important in mammalian development and neuronal function. Human ESC, hESC-derived NP, and human central nervous system stem cells were compared using Affymetrix exon arrays. We introduced an outlier detection approach, REAP (Regression-based Exon Array Protocol), to identify 1,737 internal exons that are predicted to undergo AS in NP compared to hESC. Experimental validation of REAP-predicted AS events indicated a threshold-dependent sensitivity ranging from 56% to 69%, at a specificity of 77% to 96%. REAP predictions significantly overlapped sets of alternative events identified using expressed sequence tags and evolutionarily conserved AS events. Our results also reveal that focusing on differentially expressed genes between hESC and NP will overlook 14% of potential AS genes. In addition, we found that REAP predictions are enriched in genes encoding serine/threonine kinase and helicase activities. An example is a REAP-predicted alternative exon in the SLK (serine/threonine kinase 2) gene that is differentially included in hESC, but skipped in NP as well as in other differentiated tissues. Lastly, comparative sequence analysis revealed conserved intronic cis-regulatory elements such as the FOX1/2 binding site GCAUG as being proximal to candidate AS exons, suggesting that FOX1/2 may participate in the regulation of AS in NP and hESC. In summary, a new methodology for exon array analysis was introduced, leading to new insights into the complexity of AS in human embryonic stem cells and their transition to neural stem cells

Developing consistent data and methods to measure the public health impacts of ambient air quality for Environmental Public Health Tracking: progress to date and future directions

Environmental Public Health Tracking (EPHT) staff at the state and national levels are developing nationally consistent data and methods to estimate the impact of ozone and fine particulate matter on hospitalizations for asthma and myocardial infarction. Pilot projects have demonstrated the feasibility of pooling state hospitalization data and linking these data to The United States Environmental Protection Agency (EPA) statistically based ambient air estimates for ozone and fine particulates. Tools were developed to perform case-crossover analyses to estimate concentration–response (C-R) functions. A weakness of analyzing one state at a time is that the effects are relatively small compared to their confidence intervals. The EPHT program will explore ways to statistically combine the results of peer-reviewed analyses from across the country to provide more robust C-R functions and health impact estimates at the local level. One challenge will be to routinely share data for these types of analyses at fine geographic and temporal scales without disclosing confidential information. Another challenge will be to develop C-R estimates which take into account time, space, or other relevant effect modifiers

Atomically thin boron nitride: a tunnelling barrier for graphene devices

We investigate the electronic properties of heterostructures based on ultrathin hexagonal boron nitride (h-BN) crystalline layers sandwiched between two layers of graphene as well as other conducting materials (graphite, gold). The tunnel conductance depends exponentially on the number of h-BN atomic layers, down to a monolayer thickness. Exponential behaviour of I-V characteristics for graphene/BN/graphene and graphite/BN/graphite devices is determined mainly by the changes in the density of states with bias voltage in the electrodes. Conductive atomic force microscopy scans across h-BN terraces of different thickness reveal a high level of uniformity in the tunnel current. Our results demonstrate that atomically thin h-BN acts as a defect-free dielectric with a high breakdown field; it offers great potential for applications in tunnel devices and in field-effect transistors with a high carrier density in the conducting channel.Comment: 7 pages, 5 figure

MBA: a literature mining system for extracting biomedical abbreviations

<p>Abstract</p> <p>Background</p> <p>The exploding growth of the biomedical literature presents many challenges for biological researchers. One such challenge is from the use of a great deal of abbreviations. Extracting abbreviations and their definitions accurately is very helpful to biologists and also facilitates biomedical text analysis. Existing approaches fall into four broad categories: rule based, machine learning based, text alignment based and statistically based. State of the art methods either focus exclusively on acronym-type abbreviations, or could not recognize rare abbreviations. We propose a systematic method to extract abbreviations effectively. At first a scoring method is used to classify the abbreviations into acronym-type and non-acronym-type abbreviations, and then their corresponding definitions are identified by two different methods: text alignment algorithm for the former, statistical method for the latter.</p> <p>Results</p> <p>A literature mining system MBA was constructed to extract both acronym-type and non-acronym-type abbreviations. An abbreviation-tagged literature corpus, called Medstract gold standard corpus, was used to evaluate the system. MBA achieved a recall of 88% at the precision of 91% on the Medstract gold-standard EVALUATION Corpus.</p> <p>Conclusion</p> <p>We present a new literature mining system MBA for extracting biomedical abbreviations. Our evaluation demonstrates that the MBA system performs better than the others. It can identify the definition of not only acronym-type abbreviations including a little irregular acronym-type abbreviations (e.g., <CNS1, cyclophilin seven suppressor>), but also non-acronym-type abbreviations (e.g., <Fas, CD95>).</p

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

Coordinated optimization of visual cortical maps (I) Symmetry-based analysis

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of OP columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about an hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference.Comment: 90 pages, 16 figure

Highly Sensitive Detection of Individual HEAT and ARM Repeats with HHpred and COACH

BACKGROUND:HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. METHODOLOGY AND PRINCIPAL FINDINGS:Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. SIGNIFICANCE:A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high sensitivity at a low false positive rate and will therefore greatly enhance the accuracy of predictions of HEAT and ARM domains