Efficient targeting to storage granules of human proinsulins with altered propeptide domain.

In neuronal and endocrine cells, peptide hormones are selectively segregated into storage granules, while other proteins are exported continuously without storage. Sorting of hormones by cellular machinery involves the recognition of specific structural domains on prohormone molecules. Since the propeptide of insulin is known to play an important role in its three-dimensional structure, it is reasonable to speculate that targeting of proinsulin to storage granules would require a functional connecting peptide. To test this hypothesis, we constructed two mutations in human proinsulin with different predicted structures. In one mutation, Ins delta C, the entire C peptide was deleted, resulting in an altered insulin in which the B and the A chains are joined contiguously. In the other mutation, Ins/IGF, the C peptide of proinsulin was replaced with the unrelated 12-amino acid connecting peptide of human insulin-like growth factor-I; this substitution should permit correct folding of the B and A chains to form a tertiary structure similar to that of proinsulin. By several biochemical and morphological criteria, we found that Ins/IGF is efficiently targeted to storage granules, suggesting that the C peptide of proinsulin does not contain necessary sorting information. Unexpectedly, Ins delta C, which presumably cannot fold properly, is also targeted to granules at a high efficiency. These results imply that either the targeting machinery can tolerate changes in the tertiary structure of transported proteins, or that the B and A chains of insulin can form a relatively intact three-dimensional structure even in the absence of C peptide

Spatial and temporal patterns of Pseudo-nitzschia genetic diversity in the North Pacific Ocean from the Continuous Plankton Recorder survey

Several species of the marine diatom Pseudo-nitzschia can produce the neurotoxin domoic acid that is responsible for the seafood-borne illness amnesic shellfish poisoning in humans, marine wildlife mortalities and prolonged closures of fisheries resulting in economic losses to coastal communities. Since the year 2000, Pseudo-nitzschia species have been monitored in the Pacific Ocean with the Continuous Plankton Recorder (CPR). We used a combination of scanning electron microscopy with high-throughput and Sanger sequencing of CPR survey samples to compare the diversity of phytoplankton, including Pseudo-nitzschia species, from the north-eastern Pacific Ocean over 3 climatically different years: 2002, 2005 and 2008. A Pseudo-nitzschia-specific primer set targeting a partial region of the large subunit ribosomal DNA (rDNA) revealed spatially separated communities of Pseudo-nitzschia. The coastal region was dominated by a diverse array of P. fraudulenta unique sequences (operational taxonomic units), whereas the offshore region was rich in P. multiseries and contained a wide range of other Pseudo-nitzschia taxa, many not previously observed in this region. In 2008, exceptionally cold sea surface temperatures were recorded, influenced by a strong negative Pacific Decadal Oscillation signal. In that year, a more diverse assemblage of species was present in a spring open water sample, whereas P. fraudulenta was unusually rare from a coastal autumn sample. This is the first application of high-throughput genetic methods to uncover patterns of Pseudo-nitzschia genetic diversity from archival CPR samples, demonstrating the value of using CPR for plankton community analysis in rarely sampled regions of the oceans

Impacts of climate variability and future climate change on harmful algal blooms and human health

This is the final version of the article. Available from BioMed Central via the DOI in this record.Anthropogenically-derived increases in atmospheric greenhouse gas concentrations have been implicated in recent climate change, and are projected to substantially impact the climate on a global scale in the future. For marine and freshwater systems, increasing concentrations of greenhouse gases are expected to increase surface temperatures, lower pH, and cause changes to vertical mixing, upwelling, precipitation, and evaporation patterns. The potential consequences of these changes for harmful algal blooms (HABs) have received relatively little attention and are not well understood. Given the apparent increase in HABs around the world and the potential for greater problems as a result of climate change and ocean acidification, substantial research is needed to evaluate the direct and indirect associations between HABs, climate change, ocean acidification, and human health. This research will require a multidisciplinary approach utilizing expertise in climatology, oceanography, biology, epidemiology, and other disciplines. We review the interactions between selected patterns of large-scale climate variability and climate change, oceanic conditions, and harmful algae.This work was funded in part through grants from the NSF/NIEHS Centers for Oceans and Human Health, grant numbers NSF OCE04-32479 and NIEHS P50 ES012740 (EAL), NSF OCE-0432368 and NIEHS P50 ES012736 (LEF), NIEHS P50 ES012762 and NSF OCE-0434087 (SKM, MSP). SKM, VLT and NJM also were supported in part by the West Coast Center for Oceans and Human Health (WCCOHH) as part of the NOAA Oceans and Human Health Initiative, and this is WCCOHH publication no. 26. The WCCOHH is part of the National Marine Fisheries Service's Northwest Fisheries Science Center, Seattle, Washington

Assessing connectivity between an overlying aquifer and a coal seam gas resource using methane isotopes, dissolved organic carbon and tritium

Coal seam gas (CSG) production can have an impact on groundwater quality and quantity in adjacent or overlying aquifers. To assess this impact we need to determine the background groundwater chemistry and to map geological pathways of hydraulic connectivity between aquifers. In south-east Queensland (Qld), Australia, a globally important CSG exploration and production province, we mapped hydraulic connectivity between the Walloon Coal Measures (WCM, the target formation for gas production) and the overlying Condamine River Alluvial Aquifer (CRAA), using groundwater methane (CH4) concentration and isotopic composition (δ13C-CH4), groundwater tritium (3H) and dissolved organic carbon (DOC) concentration. A continuous mobile CH4 survey adjacent to CSG developments was used to determine the source signature of CH4 derived from the WCM. Trends in groundwater δ13C-CH4 versus CH4 concentration, in association with DOC concentration and 3H analysis, identify locations where CH4 in the groundwater of the CRAA most likely originates from the WCM. The methodology is widely applicable in unconventional gas development regions worldwide for providing an early indicator of geological pathways of hydraulic connectivity

Refined Cigar and Omega-deformed Conifold

Antoniadis et al proposed a relation between the Omega-deformation and refined correlation functions of the topological string theory. We investigate the proposal for the deformed conifold geometry from a non-compact Gepner model approach. The topological string theory on the deformed conifold has a dual description in terms of the c=1 non-critical string theory at the self-dual radius, and the Omega-deformation yields the radius deformation. We show that the refined correlation functions computed from the twisted SL(2,R)/U(1) Kazama-Suzuki coset model at level k=1 have direct c=1 non-critical string theory interpretations. After subtracting the leading singularity to procure the 1PI effective action, we obtain the agreement with the proposal.Comment: 15 pages, v2: reference added, v3: published versio

Strong correlations and orbital texture in single-layer 1T-TaSe2

Strong electron correlation can induce Mott insulating behaviour and produce intriguing states of matter such as unconventional superconductivity and quantum spin liquids. Recent advances in van der Waals material synthesis enable the exploration of Mott systems in the two-dimensional limit. Here we report characterization of the local electronic properties of single- and few-layer 1T-TaSe2 via spatial- and momentum-resolved spectroscopy involving scanning tunnelling microscopy and angle-resolved photoemission. Our results indicate that electron correlation induces a robust Mott insulator state in single-layer 1T-TaSe2 that is accompanied by unusual orbital texture. Interlayer coupling weakens the insulating phase, as shown by reduction of the energy gap and quenching of the correlation-driven orbital texture in bilayer and trilayer 1T-TaSe2. This establishes single-layer 1T-TaSe2 as a useful platform for investigating strong correlation physics in two dimensions

Observation of An Evolving Magnetic Flux Rope Prior To and During A Solar Eruption

Explosive energy release is a common phenomenon occurring in magnetized plasma systems ranging from laboratories, Earth's magnetosphere, the solar corona and astrophysical environments. Its physical explanation is usually attributed to magnetic reconnection in a thin current sheet. Here we report the important role of magnetic flux rope structure, a volumetric current channel, in producing explosive events. The flux rope is observed as a hot channel prior to and during a solar eruption from the Atmospheric Imaging Assembly (AIA) telescope on board the Solar Dynamic Observatory (SDO). It initially appears as a twisted and writhed sigmoidal structure with a temperature as high as 10 MK and then transforms toward a semi-circular shape during a slow rise phase, which is followed by fast acceleration and onset of a flare. The observations suggest that the instability of the magnetic flux rope trigger the eruption, thus making a major addition to the traditional magnetic-reconnection paradigm.Comment: 13 pages, 3 figure

Defect Perturbations in Landau-Ginzburg Models

Perturbations of B-type defects in Landau-Ginzburg models are considered. In particular, the effect of perturbations of defects on their fusion is analyzed in the framework of matrix factorizations. As an application, it is discussed how fusion with perturbed defects induces perturbations on boundary conditions. It is shown that in some classes of models all boundary perturbations can be obtained in this way. Moreover, a universal class of perturbed defects is constructed, whose fusion under certain conditions obey braid relations. The functors obtained by fusing these defects with boundary conditions are twist functors as introduced in the work of Seidel and Thomas.Comment: 46 page

Discovery (theoretical prediction and experimental observation) of a large-gap topological-insulator class with spin-polarized single-Dirac-cone on the surface

Recent theories and experiments have suggested that strong spin-orbit coupling effects in certain band insulators can give rise to a new phase of quantum matter, the so-called topological insulator, which can show macroscopic entanglement effects. Such systems feature two-dimensional surface states whose electrodynamic properties are described not by the conventional Maxwell equations but rather by an attached axion field, originally proposed to describe strongly interacting particles. It has been proposed that a topological insulator with a single spin-textured Dirac cone interfaced with a superconductor can form the most elementary unit for performing fault-tolerant quantum computation. Here we present an angle-resolved photoemission spectroscopy study and first-principle theoretical calculation-predictions that reveal the first observation of such a topological state of matter featuring a single-surface-Dirac-cone realized in the naturally occurring Bi$_2$Se$_3$ class of materials. Our results, supported by our theoretical predictions and calculations, demonstrate that undoped compound of this class of materials can serve as the parent matrix compound for the long-sought topological device where in-plane surface carrier transport would have a purely quantum topological origin. Our study further suggests that the undoped compound reached via n-to-p doping should show topological transport phenomena even at room temperature.Comment: 3 Figures, 18 pages, Submitted to NATURE PHYSICS in December 200

Cavity formation on the surface of a body entering water with deceleration

The two-dimensional water entry of a rigid symmetric body with account for cavity formation on the body surface is studied. Initially the liquid is at rest and occupies the lower half plane. The rigid symmetric body touches the liquid free surface at a single point and then starts suddenly to penetrate the liquid vertically with a time-varying speed. We study the effect of the body deceleration on the pressure distribution in the flow region. It is shown that, in addition to the high pressures expected from the theory of impact, the pressure on the body surface can later decrease to sub-atmospheric levels. The creation of a cavity due to such low pressures is considered. The cavity starts at the lowest point of the body and spreads along the body surface forming a thin space between a new free surface and the body. Within the linearised hydrodynamic problem, the positions of the two turnover points at the periphery of the wetted area are determined by Wagner’s condition. The ends of the cavity’s free surface are modelled by the Brillouin–Villat condition. The pressure in the cavity is assumed to be a prescribed constant, which is a parameter of the model. The hydrodynamic problem is reduced to a system of integral and differential equations with respect to several functions of time. Results are presented for constant deceleration of two body shapes: a parabola and a wedge. The general formulation made also embraces conditions where the body is free to decelerate under the total fluid force. Contrasts are drawn between results from the present model and a simpler model in which the cavity formation is suppressed. It is shown that the expansion of the cavity can be significantly slower than the expansion of the corresponding zone of sub-atmospheric pressure in the simpler model. For forced motion and cavity pressure close to atmospheric, the cavity grows until almost complete detachment of the fluid from the body. In the problem of free motion of the body, cavitation with vapour pressure in the cavity is achievable only for extremely large impact velocities