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Sökning: WFRF:(Stern Gary A)

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1.
  • Aad, G, et al. (författare)
  • 2015
  • swepub:Mat__t
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  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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4.
  • Wang, Li-San, et al. (författare)
  • Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
  • 2015
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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5.
  • Bidleman, Terry Frank, et al. (författare)
  • Scavenging amphipods : sentinels for penetration of mercury and persistent organic chemicals into food webs of the deep arctic ocean
  • 2013
  • Ingår i: Environmental Science and Technology. - Washington : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 47:11, s. 5553-5561
  • Tidskriftsartikel (refereegranskat)abstract
    • Archived specimens of the scavenging amphipod Eurythenes gryllus, collected from 2075 to 4250 m below the surface on five expeditions to the western and central Arctic Ocean between 1983 and 1998, were analyzed for total mercury (∑Hg), methyl mercury (MeHg), polychlorinated biphenyls (PCBs) and other industrial or byproduct organochlorines (chlorobenzenes, pentachloroanisole, octachlorostyrene), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs). Median ∑Hg concentrations ranged from 70 to 366 ng g(-1) wet weight (ww). MeHg concentrations (3.55 to 23.5 ng g(-1) ww) accounted for 1.7 to 20.1% (median 3.7%) of ∑Hg. ∑Hg and MeHg were positively and significantly correlated with ww (∑Hg r(2) = 0.18, p = 0.0004, n = 63; MeHg r(2) = 0.42, p = 0.0004, n = 25), but not significantly with δ(13)C nor δ(15)N. Median concentrations of total persistent organic pollutants (POPs) ranged from 9750 to 156 000 ng g(-1) lipid weight, with order of abundance: ∑TOX (chlorobornanes quantified as technical toxaphene) > ∑PCBs > ∑DDTs > ∑chlordanes > ∑mirex compounds > ∑BDEs ∼ ∑chlorobenzenes ∼ octachlorostyrene > α-hexachlorocyclohexane ∼ hexachlorobenzene ∼ pentachloroanisole. Enantioselective accumulation was found for the chiral OCPs o,p'-DDT, cis- and trans-chlordane, nonachlor MC6 and oxychlordane. Lipid-normalized POPs concentrations were elevated in amphipods with lipid percentages ≤10%, suggesting that utilization of lipids resulted in concentration of POPs in the remaining lipid pool. Multidimensional Scaling (MDS) analysis using log-transformed physiological variables and lipid-normalized organochlorine concentrations distinguished amphipods from the central vs western arctic stations. This distinction was also seen for PCB homologues, whereas profiles of other compound classes were more related to specific stations rather than central-west differences.
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  • Pućko, Monika, et al. (författare)
  • Current use pesticide and legacy organochlorine pesticide dynamics at the ocean-sea ice-atmosphere interface in resolute passage, Canadian Arctic, during winter-summer transition
  • 2017
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 580, s. 1460-1469
  • Tidskriftsartikel (refereegranskat)abstract
    • Here, we present the first detailed analysis of processes by which various current use pesticides (CUPs) and legacy organochlorine pesticides (OCPs) are concentrated in melt ponds that form on Arctic sea ice in the summer, when surface snow is melting and ice eventually breaks up. Four current use pesticides (dacthal, chlorpyrifos, trifluralin, and pentachloronitrobenzene) and one legacy organochlorine pesticide (α-hexachlorocyclohexane) were detected in ponds in Resolute Passage, Canadian Arctic, in 2012. Melt-pond concentrations changed over time as a function of gas exchange, precipitation, and dilution with melting sea ice. Observed increases in melt-pond concentrations for all detected pesticides were associated with precipitation events. Dacthal reached the highest concentration of all current use pesticides in ponds (95 ± 71 pg L− 1), a value exceeding measured concentrations in the under-ice (0 m) and 5 m seawater by > 10 and > 16 times, respectively. Drainage of dacthal-enriched pond water to the ocean during ice break-up provides an important ice-mediated annual delivery route, adding ~ 30% of inventory in the summer Mixed Layer (ML; 10 m) in the Resolute Passage, and a concentrating mechanism with potential implications for exposures to organisms such as ice algae, and phytoplankton.
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9.
  • Pućko, Monika, et al. (författare)
  • The delivery of organic contaminants to the Arctic food web : why sea ice matters
  • 2015
  • Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 506–507, s. 444-452
  • Tidskriftsartikel (refereegranskat)abstract
    • For decades sea ice has been perceived as a physical barrier for the loading of contaminants to the Arctic Ocean. We show that sea ice, in fact, facilitates the delivery of organic contaminants to the Arctic marine food web through processes that: 1) are independent of contaminant physical–chemical properties (e.g. 2–3-fold increase in exposure to brine-associated biota), and 2) depend on physical–chemical properties and, therefore, differentiate between contaminants (e.g. atmospheric loading of contaminants to melt ponds over the summer, and their subsequent leakage to the ocean). We estimate the concentrations of legacy organochlorine pesticides (OCPs) and current-use pesticides (CUPs) in melt pond water in the Beaufort Sea, Canadian High Arctic, in 2008, at near-gas exchange equilibrium based on Henry's law constants (HLCs), air concentrations and exchange dynamics. CUPs currently present the highest risk of increased exposures through melt pond loading and drainage due to the high ratio of melt pond water to seawater concentration (Melt pond Enrichment Factor, MEF), which ranges from 2 for dacthal to 10 for endosulfan I. Melt pond contaminant enrichment can be perceived as a hypothetical ‘pump’ delivering contaminants from the atmosphere to the ocean under ice-covered conditions, with 2–10% of CUPs annually entering the Beaufort Sea via this input route compared to the standing stock in the Polar Mixed Layer of the ocean. The abovementioned processes are strongly favored in first-year ice compared to multi-year ice and, therefore, the dynamic balance between contaminant inventories and contaminant deposition to the surface ocean is being widely affected by the large-scale icescape transition taking place in the Arctic.
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10.
  • Wong, Fiona, et al. (författare)
  • Air-Water Exchange of Anthropogenic and Natural Organohalogens on International Polar Year (IPY) Expeditions in the Canadian Arctic
  • 2011
  • Ingår i: Environmental Science and Technology. - : AMER CHEMICAL SOC. - 0013-936X .- 1520-5851. ; 45:3, s. 876-881
  • Tidskriftsartikel (refereegranskat)abstract
    • Shipboard measurements of organohalogen compounds in air and surface seawater were conducted in the Canadian Arctic in 2007-2008. Study areas included the Labrador Sea, Hudson Bay, and the southern Beaufort Sea. High volume air samples were collected at deck level (6 m), while low volume samples were taken at 1 and 15 m above the water or ice surface. Water samples were taken within 7 m. Water concentration ranges (pg L-1) were as follows: alpha-hexachlorocyclohexane (alpha-HCH) 465-1013, gamma-HCH 150-254, hexachlorobenzene (HCB) 4.0-6.4, 2,4-dibromoanisole (DBA) 8.5-38, and 2,4,6-tribromoanisole (TBA) 4.7-163. Air concentration ranges (pg m(-3)) were as follows: alpha-HCH 7.5-48, gamma-HCH 2.1-7.7, HCB 48-71, DBA 4.8-25, and TBA 6.4 - 39. Fugacity gradients predicted net deposition of HCB in all areas, while exchange directions varied for the other chemicals by season and locations. Net evasion of alpha-HCH from Hudson Bay and the Beaufort Sea during open water conditions was shown by air concentrations that averaged 14% higher at 1 m than 15 m. No significant difference between the two heights was found over ice cover. The alpha-HCH in air over the Beaufort Sea was racemic in winter (mean enantiomer fraction, EF = 0.504 +/- 0.008) and nonracemic in late spring-early summer (mean EF = 0.476 +/- 0.010). This decrease in EF was accompanied by a rise in air concentrations due to volatilization of nonracemic alpha-HCH from surface water (EF = 0.457 +/- 0.019). Fluxes of chemicals during the southern Beaufort Sea open water season (i.e., Leg 9) were estimated using the Whitman two-film model, where volatilization fluxes are positive and deposition fluxes are negative. The means +/- SD (and ranges) of net fluxes (ng m(-2) d(-1)) were as follows: alpha-HCH 6.8 +/- 3.2 (2.7-13), gamma-HCH 0.76 +/- 0.40 (0.26-1.4), HCB -9.6 +/- 2.7 (-6.1 to -15), DBA 1.2 +/- 0.69 (0.04-2.0), and TBA 0.46 +/- 1.1 ng m(-2) d(-1) (-1.6 to 2.0).
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