199 research outputs found
Teleconnected warm and cold extremes of North American wintertime temperatures
Current models for spatial extremes are concerned with the joint upper (or
lower) tail of the distribution at two or more locations. Such models cannot
account for teleconnection patterns of two-meter surface air temperature
() in North America, where very low temperatures in the contiguous
Unites States (CONUS) may coincide with very high temperatures in Alaska in the
wintertime. This dependence between warm and cold extremes motivates the need
for a model with opposite-tail dependence in spatial extremes. This work
develops a statistical modeling framework which has flexible behavior in all
four pairings of high and low extremes at pairs of locations. In particular, we
use a mixture of rotations of common Archimedean copulas to capture various
combinations of four-corner tail dependence. We study teleconnected
extremes using ERA5 reanalysis of daily average two-meter temperature during
the boreal winter. The estimated mixture model quantifies the strength of
opposite-tail dependence between warm temperatures in Alaska and cold
temperatures in the midlatitudes of North America, as well as the reverse
pattern. These dependence patterns are shown to correspond to blocked and zonal
patterns of mid-tropospheric flow. This analysis extends the classical notion
of correlation-based teleconnections to considering dependence in higher
quantiles
A MOLECULAR ANALYSIS OF PROTEIN TRAFFICKING IN THE VERTEBRATE RETINA: IMPLICATIONS FOR INTRAFLAGELLAR TRANSPORT AND DISEASE
Vertebrate photoreceptors are highly specialized sensory neurons that utilize a
modified cilium known as the outer segment to detect light. Proper trafficking of
proteins to the outer segment is essential for photoreceptor function and survival and
defects in this process lead to retinal disease. In this dissertation I focus on two aspects
of protein trafficking, intracellular vesicular trafficking in photoreceptors and retinal
pigmented epithelial (RPE) cells and how it relates to the human disease choroideremia
(CHM), and the trafficking of proteins through the photoreceptor cilium. The human
retinal degenerative disease choroideremia (CHM) is caused by mutation of the Rab
escort protein-1 (REP1) gene, which is required for proper intracellular vesicular
trafficking. However, it was unclear whether photoreceptor degeneration in this disease
is cell-autonomous, due to defective opsin transport within the photoreceptor, or is
noncell-autonomous and a secondary consequence of defective RPE. Utilizing the
technique of blastomere transplantation and a zebrafish line with a mutation in the rep1 gene, I show that photoreceptor degeneration in CHM is noncell-autonomous and is
caused by defective RPE.
The molecular machinery responsible for protein trafficking through the
photoreceptor cilium remained unclear for a long time. Recent studies found
Intraflagellar Transport (IFT) is the process that mediates cilia formation and transport
of proteins through a cilium, and further analyses showed IFT is important for
trafficking proteins to the outer segment. However, many details about how IFT works
in photoreceptors remained unclear. By analyzing zebrafish harboring a null mutation in
the ift57 gene, I show that Ift57 is only required for efficient IFT, and that the Ift57
protein plays a role in the ATP-dependent dissociation of kinesin II from the IFT
particle. Lastly, I investigate the role of retrograde IFT in photoreceptors, a process that
had yet to be investigated. By utilizing antisense morpholino oligonucleotides to inhibit
expression of cytoplasmic dynein-2 (the molecular motor that mediates retrograde IFT) ,
I show that retrograde IFT is required for outer segment extension and the recycling of
IFT proteins
The intraflagellar transport protein IFT57 is required for cilia maintenance and regulates IFT-particle–kinesin-II dissociation in vertebrate photoreceptors
SUMMARY: Defects in protein transport within vertebrate photoreceptors can result in photoreceptor degeneration. In developing and mature photoreceptors, proteins targeted to the outer segment are transported through the connecting cilium via the process of intraflagellar transport (IFT). In studies of vertebrate IFT, mutations in any component of the IFT particle typically abolish ciliogenesis, suggesting that IFT proteins are equally required for IFT. To determine whether photoreceptor outer segment formation depends equally on individual IFT proteins, we compared the retinal phenotypes of IFT57 and IFT88 mutant zebrafish. IFT88 mutants failed to form outer segments, whereas IFT57 mutants formed short outer segments with reduced amounts of opsin. Our phenotypic analysis revealed that IFT57 is not essential for IFT, but is required for efficient IFT. In co-immunoprecipitation experiments from whole-animal extracts, we determined that kinesin II remained associated with the IFT particle in the absence of IFT57, but IFT20 did not. Additionally, kinesin II did not exhibit ATP-dependent dissociation from the IFT particle in IFT57 mutants. We conclude that IFT20 requires IFT57 to associate with the IFT particle and that IFT57 and/or IFT20 mediate kinesin II dissociation
Structure and toxicity of AZA-59, an azaspiracid shellfish poisoning toxin produced by Azadinium poporum (Dinophyceae)
To date, the putative shellfish toxin azaspiracid 59 (AZA-59) produced by Azadinium poporum (Dinophyceae) has been the only AZA found in isolates from the Pacific Northwest coast of the USA (Northeast Pacific Ocean). Anecdotal reports of sporadic diarrhetic shellfish poisoning-like illness, with the absence of DSP toxin or Vibrio contamination, led to efforts to look for other potential toxins, such as AZAs, in water and shellfish from the region. A. poporum was found in Puget Sound and the outer coast of Washington State, USA, and a novel AZA (putative AZA-59) was detected in low quantities in SPATT resins and shellfish. Here, an A. poporum strain from Puget Sound was mass-cultured and AZA-59 was subsequently purified and structurally characterized. In vitro cytotoxicity of AZA-59 towards Jurkat T lymphocytes and acute intraperitoneal toxicity in mice in comparison to AZA-1 allowed the derivation of a provisional toxicity equivalency factor of 0.8 for AZA-59. Quantification of
AZA-59 using ELISA and LC-MS/MS yielded reasonable quantitative results when AZA-1 was used as an external reference standard. This study assesses the toxic potency of AZA-59 and will inform guidelines for its potential monitoring in case of increasing toxin levels in edible shellfish
Imaging early endothelial inflammation following stroke by core shell silica superparamagnetic glyconanoparticles that target selectin
Activation of the endothelium is a pivotal first step for leukocyte migration into the diseased brain. Consequently, imaging this activation process is highly desirable. We synthesized carbohydrate-functionalized magnetic nanoparticles that bind specifically to the endothelial transmembrane inflammatory proteins E and P selectin. Magnetic resonance imaging revealed that the targeted nanoparticles accumulated in the brain vasculature following acute administration into a clinically relevant animal model of stroke, though increases in selectin expression were observed in both brain hemispheres. Nonfunctionalized naked particles also appear to be a plausible agent to target the ischemic vasculature. The importance of these findings is discussed regarding the potential for translation into the clinic
Plankton Multiproxy Analyses in the Northern Patagonian Shelf, Argentina: Community Structure, Phycotoxins, and Characterization of Toxic Alexandrium Strains
The extensive Argentine continental shelf supports high plankton productivity and fish catches. In particular, El Rincón coastal area and the adjacent shelf fronts (38.5–42°S, 58.5–62°W) comprise diverse habitats and hold species of economic and ecological value. So far, studies of the microbial community present at the base of the food web remain scarce. Here, we describe the late winter plankton (5–200 μm) structure in terms of abundance, biomass, species composition, functional groups, and phycotoxin profiles in surface waters of El Rincón in September 2015. Diatoms are the most abundant and the largest contributors to carbon biomass at most stations. They dominated the coastal and inner-shelf (depths <50 m), while dinoflagellates and small flagellates (<15 μm) dominated offshore at the middle-shelf waters (depth ∼100 m). In addition, large (>20 μm) heterotrophic protists such as various ciliates and dinoflagellates species were more abundant offshore. Scanning of phycotoxins disclosed that paralytic shellfish poisoning (PSP) toxins were dominated by gonyautoxins-1/4 (GTX1/4), whereas lipophilic toxins were detected in low abundance, for example, domoic acid (DA). However, a bloom of Pseudo-nitzschia spp. (up to 3.6 × 105 cells L-1) was detected at inner-shelf stations. Pectenotoxin-2 (PTX-2) and 13-desmethyl spirolide C (SPX-1) were the most abundant in the field. The PTX-2 co-occurred with Dinophysis spp., mainly D. tripos, while SPX-1 dominated at middle-shelf stations, where cells of Alexandrium catenella (1 strain) and A. ostenfeldii (3 strains) were isolated. The quantitative PSP profiles of the Alexandrium strains differed significantly from the in situ profiles. Moreover, the three A. ostenfeldii strains produced PSP and additionally, five novel spirolides. Phylogenetic analyses of these newly isolated strains from the South Atlantic revealed a new ribotype group, suggesting a biogeographical distinction in the population. The plankton survey presented here contributes baseline knowledge to evaluate potential ecosystem changes and track the global distribution of toxigenic species
A Molecular and Co-Evolutionary Context for Grazer Induced Toxin Production in Alexandrium tamarense
Marine dinoflagellates of the genus Alexandrium are the proximal source of neurotoxins associated with Paralytic Shellfish Poisoning. The production of these toxins, the toxin biosynthesis and, thus, the cellular toxicity can be influenced by abiotic and biotic factors. There is, however, a lack of substantial evidence concerning the toxins' ecological function such as grazing defense. Waterborne cues from copepods have been previously found to induce a species-specific increase in toxin content in Alexandrium minutum. However, it remains speculative in which context these species-specific responses evolved and if it occurs in other Alexandrium species as well. In this study we exposed Alexandrium tamarense to three copepod species (Calanus helgolandicus, Acartia clausii, and Oithona similis) and their corresponding cues. We show that the species-specific response towards copepod-cues is not restricted to one Alexandrium species and that co-evolutionary processes might be involved in these responses, thus giving additional evidence for the defensive role of phycotoxins. Through a functional genomic approach we gained insights into the underlying molecular processes which could trigger the different outcomes of these species-specific responses and consequently lead to increased toxin content in Alexandrium tamarense. We propose that the regulation of serine/threonine kinase signaling pathways has a major influence in directing the external stimuli i.e. copepod-cues, into different intracellular cascades and networks in A. tamarense. Our results show that A. tamarense can sense potential predating copepods and respond to the received information by increasing its toxin production. Furthermore, we demonstrate how a functional genomic approach can be used to investigate species interactions within the plankton community
Dysfunction of Heterotrimeric Kinesin-2 in Rod Photoreceptor Cells and the Role of Opsin Mislocalization in Rapid Cell Death
Loss of kinesin-2 function causes rapid death of rod photoreceptors. The cell death is dependent on the expression of opsin, which first accumulates along the route to the outer segment, but not on signaling by opsin-arrestin complexes or by light activation; the key element appears to be the accumulation of excessive protein in the wrong place
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