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Find video protocols related to scientific articles indexed in Pubmed.
Impact of Environmental Curium on Plutonium Migration and Isotopic Signatures.
Environ. Sci. Technol.
PUBLISHED: 10-29-2014
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Plutonium (Pu), americium (Am), and curium (Cm) activities were measured in sediments from a former radioactive waste disposal basin located on the Savannah River Site, South Carolina, and in subsurface aquifer sediments collected downgradient from the basin. In situ Kd values (Pu concentration ratio of sediment/groundwater) derived from this field data and previously reported groundwater concentration data compared well to laboratory Kd values reported in the literature. Pu isotopic signatures confirmed multiple sources of Pu contamination. The ratio of (240)Pu/(239)Pu was appreciably lower for sediment samples compared to the associated groundwater. This isotopic ratio difference may be explained by the following: (1) (240)Pu produced by decay of (244)Cm may exist predominantly in high oxidation states (Pu(V)O2(+) and Pu(VI)O2(2+)) compared to Pu derived from the disposed waste effluents, and (2) oxidized forms of Pu sorb less to sediments than reduced forms of Pu. Isotope-specific Kd values calculated from measured Pu activities in the sediments and groundwater indicated that (240)Pu, which is derived primarily from the decay of (244)Cm, had a value of 10 ± 2 mL g(-1), whereas (239)Pu originating from the waste effluents discharged at the site had a value of 101 ± 8 mL g(-1). One possible explanation for the isotope-specific sorption behavior is that (240)Pu likely existed in the weaker sorbing oxidation states, +5 or +6, than (239)Pu, which likely existed in the +3 or +4 oxidation states. Consequently, remediation strategies for radioactively contaminated systems must consider not only the discharged contaminants but also their decay products. In this case, mitigation of Cm as well as Pu will be required to completely address Pu migration from the source term.
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Cutting Edge: Failure of Antigen-Specific CD4+ T Cell Recruitment to the Kidney during Systemic Candidiasis.
J. Immunol.
PUBLISHED: 10-24-2014
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Candida albicans is the leading cause of systemic candidiasis, a fungal disease associated with high mortality and poor treatment options. The kidney is the target organ during infection and whose control is largely dependent on innate immunity, because lymphocytes appear redundant for protection. In this article, we show that this apparent redundancy stems from a failure of Ag-specific CD4(+) T cells to migrate into infected kidneys. In contrast, Ag-specific CD8(+) T cells are recruited normally. Using Ag-loaded immunoliposomes to artificially reverse this defective migration, we show that recruited Ag-specific CD4(+) T cells polarize toward a Th17 phenotype in the kidney and are protective during fungal infection. Therefore, our data explain the redundancy of CD4(+) T cells for defense against systemic infection with C. albicans and have important implications for our understanding of antifungal immunity and the control of renal infections.
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Subtotal cholecystectomy and open total cholecystectomy: alternatives in complicated cholecystitis.
Am Surg
PUBLISHED: 09-30-2014
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Subtotal cholecystectomy (SC) is an alternative to open total cholecystectomy (OTC) when variable anatomy or other intraoperative findings preclude safe dissection of Calot's triangle. The objective of this study was to compare the outcomes between SC and OTC in patients with complicated cholecystitis, cases that could not be completed with the original surgical approach and required intraoperative conversion to either SC or OTC. All cases of cholecystectomy converted to SC or OTC from January 2008 to December 2012 were retrospectively identified. Preoperative laboratory values, imaging studies, and clinical demographics were compared between the two groups. The outcome variables analyzed included hospital and intensive care unit length of stay as well as intraoperative complications. In this study, 214 cases of complicated cholecystitis were analyzed; 63 SC and 151 laparoscopic converted to OTC. From the SC group, 46 (73%) were converted to open, 12 (19%) were primary open, and five (8%) were done laparoscopically. There were no statistically significant differences in demographics, preoperative serologic markers, or intraoperative findings (P > 0.05). Five (3.3%) common bile duct (CBD) injuries occurred in the OTC group, whereas none occurred in the SC group. Overall there were 23 (15.2%) complications in the OTC group and nine (14.3%) in the SC group. The aggregate severe complication rate (CBD injury, vascular injury, gastrointestinal injury) was significantly higher in the OTC group (0.0 to 7.9%, P = 0.036). In conclusion, SC may be considered as a safe alternative in complicated cholecystitis.
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Temporal variation of iodine concentration and speciation ((127)i and (129)i) in wetland groundwater from the savannah river site, USA.
Environ. Sci. Technol.
PUBLISHED: 09-15-2014
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(129)I derived from a former radionuclide disposal basin located on the Savannah River Site (SRS) has concentrated in a wetland 600 m downstream. To evaluate temporal environmental influences on iodine speciation and mobility in this subtropical wetland environment, groundwater was collected over a three-year period (2010-2012) from a single location. Total (127)I and (129)I showed significant temporal variations, ranging from 68-196 nM for (127)I and <5-133 pCi/L for (129)I. These iodine isotopes were significantly correlated with groundwater acidity and nitrate, two parameters elevated within the contaminant plume. Additionally, (129)I levels were significantly correlated with those of (127)I, suggesting that biogeochemical controls on (127)I and (129)I are similar within the SRS aquifer/wetland system. Iodine speciation demonstrates temporal variations as well, reflecting effects from surface recharges followed by acidification of groundwater and subsequent formation of anaerobic conditions. Our results reveal a complex system where few single ancillary parameters changed in a systematic manner with iodine speciation. Instead, changes in groundwater chemistry and microbial activity, driven by surface hydrological events, interact to control iodine speciation and mobility. Future radiological risk models should consider the flux of (129)I in response to temporal changes in wetland hydrologic and chemical conditions.
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DNA Sequences Proximal to Human Mitochondrial DNA Deletion Breakpoints Prevalent in Human Disease Form G-quadruplexes, a Class of DNA Structures Inefficiently Unwound by the Mitochondrial Replicative Twinkle Helicase.
J. Biol. Chem.
PUBLISHED: 09-05-2014
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Mitochondrial DNA deletions are prominent in human genetic disorders, cancer, and aging. It is thought that stalling of the mitochondrial replication machinery during DNA synthesis is a prominent source of mitochondrial genome instability; however, the precise molecular determinants of defective mitochondrial replication are not well understood. In this work, we performed a computational analysis of the human mitochondrial genome using the "Pattern Finder" G-quadruplex (G4) predictor algorithm to assess whether G4-forming sequences reside in close proximity (within 20 base pairs) to known mitochondrial DNA deletion breakpoints. We then used this information to map G4P sequences with deletions characteristic of representative mitochondrial genetic disorders and also those identified in various cancers and aging. Circular dichroism and UV spectral analysis demonstrated that mitochondrial G-rich sequences near deletion breakpoints prevalent in human disease form G-quadruplex DNA structures. A biochemical analysis of purified recombinant human Twinkle protein (gene product of c10orf2) showed that the mitochondrial replicative helicase inefficiently unwinds well characterized intermolecular and intramolecular G-quadruplex DNA substrates, as well as a unimolecular G4 substrate derived from a mitochondrial sequence that nests a deletion breakpoint described in human renal cell carcinoma. Although G4 has been implicated in the initiation of mitochondrial DNA replication, our current findings suggest that mitochondrial G-quadruplexes are also likely to be a source of instability for the mitochondrial genome by perturbing the normal progression of the mitochondrial replication machinery, including DNA unwinding by Twinkle helicase.
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Speciation of iodine isotopes inside and outside of a contaminant plume at the Savannah River Site.
Sci. Total Environ.
PUBLISHED: 08-29-2014
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A primary obstacle in understanding the fate and transport of the toxic radionuclide (129)I (a thyroid seeker) is an accurate method to distinguish it from the stable isotope, (127)I, and to quantify the various species at environmentally relevant concentrations (~10(-8) M). A pH-dependent solvent extraction and combustion method was paired with accelerator mass spectrometry (AMS) to measure ambient levels of (129)I/(127)I isotope ratios and iodine speciation (iodide (I(-)), iodate (IO3(-)), and organo-I (OI)) in aquatic systems. The method exhibited an overall uncertainty of 10% or less for I(-) and IO3(-), and less than 30% for OI species concentrations and enabled (129)I measurements as low as 0.001 Bq/L (1 Bq/L=10(-13) M). The method was used to analyze groundwater from the Savannah River Site (SRS), South Carolina, USA, along a pH, redox potential (Eh), and organic carbon gradient (8-60 ?M DOC). The data confirmed that the (129)I/(127)I ratios and species distribution were strongly pH dependent and varied in a systematic manner from the strongly acidic source. While (129)I speciation in plume samples containing total I concentrations >1.7 Bq/L was similar whether measured by AMS or GC-MS ([I(-)]?[IO3(-)]=[OI]), AMS enabled (129)I speciation measurements at much lower concentrations than what was possible with GC-MS. AMS analyses demonstrated that groundwater samples minimally impacted by the plume were still orders of magnitude higher than ambient (129)I concentrations typically found elsewhere in the USA groundwaters and rivers. This is likely due to past atmospheric releases of volatile (129)I species by SRS nuclear reprocessing facilities near the study site. Furthermore, the results confirmed the existence of (129)I not only as I(-), but also as OI and IO3(-) species.
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A comparison between amylase levels from peritonsillar, dental, and neck abscesses.
Clin Otolaryngol
PUBLISHED: 08-13-2014
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Pus of peritonsillar abscess (PTA) contains very high amylase levels in some patients. The objective of this study is to further test this finding and to check whether high amylase levels in peritonsillar abscess originate from contamination by saliva during aspiration.
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Uranium immobilization in an iron-rich rhizosphere of a native wetland plant from the Savannah River Site under reducing conditions.
Environ. Sci. Technol.
PUBLISHED: 07-29-2014
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The hypothesis of this study was that iron plaques formed on the roots of wetland plants and their rhizospheres create environmental conditions favorable for iron reducing bacteria that promote the in situ immobilization of uranium. Greenhouse microcosm studies were conducted using native plants (Sparganium americanum) from a wetland located on the Savannah River Site, Aiken, SC. After iron plaques were established during a 73-day period by using an anoxic Fe(II)-rich nutrient solution, a U(VI) amended nutrient solution was added to the system for an additional two months. Compared to plant-free control microcosms, microcosms containing iron plaques successfully stimulated the growth of targeted iron reducing bacteria, Geobacter spp. Their population continuously increased after the introduction of the U(VI) nutrient solution. The reduction of some of the U(VI) to U(IV) by iron reducing bacteria was deduced based on the observations that the aqueous Fe(II) concentrations increased while the U(VI) concentrations decreased. The Fe(II) produced by the iron reducing bacteria was assumed to be reoxidized by the oxygen released from the roots. Advanced spectroscopic analyses revealed that a significant fraction of the U(VI) had been reduced to U(IV) and they were commonly deposited in association with phosphorus on the iron plaque.
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Long-term radiostrontium interactions and transport through sediment.
Environ. Sci. Technol.
PUBLISHED: 07-08-2014
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Radioactive strontium is one of the most common radiological contaminants in groundwater and soil. Objectives of this study were to (1) evaluate Sr transport through an 11-year-long field lysimeter study and (2) quantify secondary aging effects between Sr and sediment that may need to be considered for long-term transport modeling. Batch sorption/desorption tests were conducted with (85)Sr, (88)Sr, and (90)Sr using a sediment recovered from a field lysimeter containing a glass pellet amended with high-level nuclear waste for 24 years. Sr was largely reversibly and linearly sorbed. (85)Sr sorption coefficients (Kd, concentration ratios of solids/liquids) after a 23-day contact period were about the same as the (90)Sr desorption Kd values after a 24-year contact period: sorption Kd = 32.1 ± 3.62 mL g(-1) and desorption Kd = 43.1 ± 11.4 mL g(-1). Numerical modeling of the lysimeter (90)Sr depth profile indicated that a Kd value of 32 mL g(-1) fit the data best. The Kd construct captured most of the data trends above and below the source term, except for immediately below the source where the model clearly overestimated Sr mobility. (90)Sr desorption tests suggested that the overestimated mobility may be attributed to a second, slower sorption reaction that occurs over a course of months to decades.
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Primary care providers' bereavement care practices: recommendations for research directions.
Int J Geriatr Psychiatry
PUBLISHED: 05-17-2014
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Bereaved patients are often seen in primary care settings. Although most do not require formal support, physicians may be called upon to provide support to some bereaved, particularly those with bereavement-related mental health disorders like complicated grief and bereavement-related depression. Research evidence on physician bereavement care is scant. We make recommendations for future research in this area.
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Targeting antigens through blood dendritic cell antigen 2 on plasmacytoid dendritic cells promotes immunologic tolerance.
J. Immunol.
PUBLISHED: 05-14-2014
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The C-type lectin receptor blood dendritic cell Ag 2 (BDCA2) is expressed exclusively on human plasmacytoid DCs (pDCs) and plays a role in Ag capture, internalization, and presentation to T cells. We used transgenic mice that express human BDCA2 and anti-BDCA2 mAbs to deliver Ags directly to BDCA2 on pDCs in vivo. Targeting Ag to pDCs in this manner resulted in significant suppression of Ag-specific CD4(+) T cell and Ab responses upon secondary exposure to Ag in the presence of adjuvant. Suppression of Ab responses required both a decrease in effector CD4(+) T cells and preservation of Foxp3(+) regulatory T cells (Tregs). Reduction in Treg numbers following Ag delivery to BDCA2 restored both CD4(+) T cell activation and Ab responses, demonstrating that Tregs were required for the observed tolerance. Our results demonstrate that Ag delivery to pDCs through BDCA2 is an effective method to induce immunological tolerance, which may be useful for treating autoimmune diseases or to inhibit unwanted Ab responses.
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Acute mastoiditis in children under 15 years of age in Southern Israel following the introduction of pneumococcal conjugate vaccines: a 4-year retrospective study (2009-2012).
Int. J. Pediatr. Otorhinolaryngol.
PUBLISHED: 04-05-2014
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To describe the epidemiologic, microbiologic, clinical and therapeutic aspects of acute mastoiditis (AM) in children <15 years of age during the 4-year period (2009-2012) following the introduction of pneumococcal conjugate vaccines in Israel.
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Plutonium immobilization and remobilization by soil mineral and organic matter in the far-field of the Savannah River Site, U.S.
Environ. Sci. Technol.
PUBLISHED: 03-04-2014
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To study the effects of natural organic matter (NOM) on Pu sorption, Pu(IV) and (V) were amended at environmentally relevant concentrations (10(-14) M) to two soils of contrasting particulate NOM concentrations collected from the F-Area of the Savannah River Site. More Pu(IV) than (V) was bound to soil colloidal organic matter (COM). A de-ashed humic acid (i.e., metals being removed) scavenged more Pu(IV,V) into its colloidal fraction than the original HA incorporated into its colloidal fraction, and an inverse trend was thus observed for the particulate-fraction-bound Pu for these two types of HAs. However, the overall Pu binding capacity of HA (particulate + colloidal-Pu) decreased after de-ashing. The presence of NOM in the F-Area soil did not enhance Pu fixation to the organic-rich soil when compared to the organic-poor soil or the mineral phase from the same soil source, due to the formation of COM-bound Pu. Most importantly, Pu uptake by organic-rich soil decreased with increasing pH because more NOM in the colloidal size desorbed from the particulate fraction in the elevated pH systems, resulting in greater amounts of Pu associated with the COM fraction. This is in contrast to previous observations with low-NOM sediments or minerals, which showed increased Pu uptake with increasing pH levels. This demonstrates that despite Pu immobilization by NOM, COM can convert Pu into a more mobile form.
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Superoxide production by a manganese-oxidizing bacterium facilitates iodide oxidation.
Appl. Environ. Microbiol.
PUBLISHED: 02-21-2014
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The release of radioactive iodine (i.e., iodine-129 and iodine-131) from nuclear reprocessing facilities is a potential threat to human health. The fate and transport of iodine are determined primarily by its redox status, but processes that affect iodine oxidation states in the environment are poorly characterized. Given the difficulty in removing electrons from iodide (I(-)), naturally occurring iodide oxidation processes require strong oxidants, such as Mn oxides or microbial enzymes. In this study, we examine iodide oxidation by a marine bacterium, Roseobacter sp. AzwK-3b, which promotes Mn(II) oxidation by catalyzing the production of extracellular superoxide (O2(-)). In the absence of Mn(2+), Roseobacter sp. AzwK-3b cultures oxidized ?90% of the provided iodide (10 ?M) within 6 days, whereas in the presence of Mn(II), iodide oxidation occurred only after Mn(IV) formation ceased. Iodide oxidation was not observed during incubations in spent medium or with whole cells under anaerobic conditions or following heat treatment (boiling). Furthermore, iodide oxidation was significantly inhibited in the presence of superoxide dismutase and diphenylene iodonium (a general inhibitor of NADH oxidoreductases). In contrast, the addition of exogenous NADH enhanced iodide oxidation. Taken together, the results indicate that iodide oxidation was mediated primarily by extracellular superoxide generated by Roseobacter sp. AzwK-3b and not by the Mn oxides formed by this organism. Considering that extracellular superoxide formation is a widespread phenomenon among marine and terrestrial bacteria, this could represent an important pathway for iodide oxidation in some environments.
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Aqueous (99)Tc, (129)I and (137)Cs removal from contaminated groundwater and sediments using highly effective low-cost sorbents.
J Environ Radioact
PUBLISHED: 01-27-2014
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Technetium-99 ((99)Tc), iodine-129 ((129)I), and cesium-137 ((137)Cs) are among the key risk-drivers for environmental cleanup. Immobilizing these radionuclides, especially TcO4(-) and I(-), has been challenging. TcO4(-) and I(-) bind very weakly to most sediments, such that distribution coefficients (Kd values; radionuclide concentration ratio of solids to liquids) are typically <2 mL/g; while Cs sorbs somewhat more strongly (Kd ? 50 mL/g). The objective of this laboratory study was to evaluate 13 cost-effective sorbents for TcO4(-), I(-), and Cs(+) uptake from contaminated groundwater and sediments. Two organoclays sorbed large amounts of TcO4(-) (Kd > 1 × 10(5) mL/g), I(-) (Kd ? 1 × 10(4) mL/g), and Cs(+) (Kd > 1 × 10(3) mL/g) and also demonstrated a largely irreversible binding of the radionuclides. Activated carbon GAC 830 was effective at sorbing TcO4(-) (Kd > 1 × 10(5) mL/g) and I(-) (Kd = 6.9 × 10(3) mL/g), while a surfactant modified chabazite was effective at sorbing TcO4(-) (Kd > 2.5 × 10(4) mL/g) and Cs(+) (Kd > 6.5 × 10(3) mL/g). Several sorbents were effective for only one radionuclide, e.g., modified zeolite Y had TcO4(-)Kd > 2.3 × 10(5) mL/g, AgS had I(-) Kd = 2.5 × 10(4) mL/g, and illite, chabazite, surfactant modified clinoptilolite, and thiol-SAMMS had Cs(+)Kd > 10(3) mL/g. These low-cost and high capacity sorbents may provide a sustainable solution for environmental remediation.
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Impact of Age-Associated Cyclopurine Lesions on DNA Repair Helicases.
PLoS ONE
PUBLISHED: 01-01-2014
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8,5' cyclopurine deoxynucleosides (cPu) are locally distorting DNA base lesions corrected by nucleotide excision repair (NER) and proposed to play a role in neurodegeneration prevalent in genetically defined Xeroderma pigmentosum (XP) patients. In the current study, purified recombinant helicases from different classifications based on sequence homology were examined for their ability to unwind partial duplex DNA substrates harboring a single site-specific cPu adduct. Superfamily (SF) 2 RecQ helicases (RECQ1, BLM, WRN, RecQ) were inhibited by cPu in the helicase translocating strand, whereas helicases from SF1 (UvrD) and SF4 (DnaB) tolerated cPu in either strand. SF2 Fe-S helicases (FANCJ, DDX11 (ChlR1), DinG, XPD) displayed marked differences in their ability to unwind the cPu DNA substrates. Archaeal Thermoplasma acidophilum XPD (taXPD), homologue to the human XPD helicase involved in NER DNA damage verification, was impeded by cPu in the non-translocating strand, while FANCJ was uniquely inhibited by the cPu in the translocating strand. Sequestration experiments demonstrated that FANCJ became trapped by the translocating strand cPu whereas RECQ1 was not, suggesting the two SF2 helicases interact with the cPu lesion by distinct mechanisms despite strand-specific inhibition for both. Using a protein trap to simulate single-turnover conditions, the rate of FANCJ or RECQ1 helicase activity was reduced 10-fold and 4.5-fold, respectively, by cPu in the translocating strand. In contrast, single-turnover rates of DNA unwinding by DDX11 and UvrD helicases were only modestly affected by the cPu lesion in the translocating strand. The marked difference in effect of the translocating strand cPu on rate of DNA unwinding between DDX11 and FANCJ helicase suggests the two Fe-S cluster helicases unwind damaged DNA by distinct mechanisms. The apparent complexity of helicase encounters with an unusual form of oxidative damage is likely to have important consequences in the cellular response to DNA damage and DNA repair.
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Immune mediated shaping of microflora community composition depends on barrier site.
PLoS ONE
PUBLISHED: 01-01-2014
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Barrier surfaces, such as the intestinal lining and the skin, are colonized by a diverse community of commensal microorganisms. Although commensal microorganisms clearly impact the host immune system, whether the immune system also shapes the commensal community is poorly understood. We used 16S rDNA deep sequencing to test whether mice with specific immune defects have an altered commensal microflora. Initially, skin swabs were obtained from wild-type and Langerhans Cell (LC) deficient mice. Despite the intimate contacts that LC make with the upper epidermis, no significant differences were observed in microbial community composition. Similarly, the skin of MyD88/TRIF(-/-), Rag1(-/-) and heterozygous littermate controls showed no alteration in their commensal communities. Next we examined mouth swabs and feces. We did not find a difference in the MyD88/TRIF(-/-) mice. However, we did observe a significant shift in the microbial composition in the feces and mouths of Rag1(-/-) mice. Thus, we conclude that the adaptive immune system modulates the microbial composition at mucosal surfaces in the steady-state but LC, adaptive immunity, and MyD88-dependent innate responses do not affect the skin microbiome revealing a major distinction between barrier sites.
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The Replication Initiation Protein Sld2 Regulates Helicase Assembly.
J. Biol. Chem.
PUBLISHED: 12-04-2013
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Assembly of the Cdc45-Mcm2-7-GINS (CMG) replicative helicase complex must be regulated to ensure that DNA unwinding is coupled with DNA synthesis. Sld2 is required for the initiation of DNA replication in budding yeast. We identified a mutant of Sld2, Sld2-m1,4, that is specifically defective in Mcm2-7 binding. When this sld2-m1,4 mutant is expressed, cells exhibit severe inhibition of DNA replication. Furthermore, the CMG complex assembles prematurely in G1 in mutant cells, but not wild-type cells. These data suggest that Sld2 binding to Mcm2-7 is essential to block the inappropriate formation of a CMG helicase complex in G1. We also study a mutant of Sld2 that is defective in binding DNA, sld2-DNA, and find that sld2-DNA cells exhibit no GINS-Mcm2-7 interaction. These data suggest that Sld2 association with DNA is required for CMG assembly in S phase.
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Intestinal lamina propria dendritic cells maintain T cell homeostasis but do not affect commensalism.
J. Exp. Med.
PUBLISHED: 09-09-2013
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Dendritic cells (DCs) in the intestinal lamina propria (LP) are composed of two CD103(+) subsets that differ in CD11b expression. We report here that Langerin is expressed by human LP DCs and that transgenic human langerin drives expression in CD103(+)CD11b(+) LP DCs in mice. This subset was ablated in huLangerin-DTA mice, resulting in reduced LP Th17 cells without affecting Th1 or T reg cells. Notably, cognate DC-T cell interactions were not required for Th17 development, as this response was intact in huLangerin-Cre I-A?(fl/fl) mice. In contrast, responses to intestinal infection or flagellin administration were unaffected by the absence of CD103(+)CD11b(+) DCs. huLangerin-DTA x BatF3(-/-) mice lacked both CD103(+) LP DC subsets, resulting in defective gut homing and fewer LP T reg cells. Despite these defects in LP DCs and resident T cells, we did not observe alterations of intestinal microbial communities. Thus, CD103(+) LP DC subsets control T cell homeostasis through both nonredundant and overlapping mechanisms.
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Iodine-129 and iodine-127 speciation in groundwater at the hanford site, US: iodate incorporation into calcite.
Environ. Sci. Technol.
PUBLISHED: 08-19-2013
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The geochemical transport and fate of radioiodine depends largely on its chemical speciation that is greatly affected by environmental factors. This study reports, for the first time, the speciation of stable and radioactive iodine in the groundwater from the Hanford Site. Iodate was the dominant species and accounted for up to 84% of the total iodine present. The alkaline pH (pH ? 8) and predominantly oxidizing environment may have prevented reduction of the iodate. In addition, groundwater samples were found to have large amounts of calcite precipitate which were likely formed as a result of CO2 degassing during removal from the deep subsurface (>70m depth). Further analyses indicated that between 7 and 40% of the dissolved (127)I and (129)I that was originally in the groundwater had coprecipitated in the calcite. Iodate was the main species incorporated into calcite and this incorporation process could be impeded by elevating the pH and decreasing ionic strength in groundwater. This study provides critical information for predicting the long-term fate and transport of (129)I. Furthermore, the common sampling artifact resulting in the precipitation of calcite by degassing CO2, had the unintended consequence of providing insight into a potential solution for the in situ remediation of groundwater (129)I.
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Sudden hearing loss with simultaneous posterior semicircular canal BPPV: Possible etiology and clinical implications.
Am J Otolaryngol
PUBLISHED: 08-10-2013
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The objectives of this study were to describe the clinical course and outcome of patients with sudden sensorineural hearing loss (SSNHL) in conjunction with benign paroxysmal positional vertigo (BPPV), and hypothesize the possible pathophysiology of this entity.
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Head shaking during Dix-Hallpike exam increases the diagnostic yield of posterior semicircular canal BPPV.
Otol. Neurotol.
PUBLISHED: 08-10-2013
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To examine whether shaking the head during the DH exam (HSDH) may improve diagnosis of posterior semicircular canal benign paroxysmal positional vertigo (pBPPV) in patients with a negative Dix-Hallpike (DH) examination.
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Radioiodine concentrated in a wetland.
J Environ Radioact
PUBLISHED: 07-09-2013
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Most subsurface environmental radioactivity contamination is expected to eventually resurface in riparian zones, or wetlands. There are a number of extremely sharp biogeochemical interfaces in wetlands that could alter radionuclide speciation and promote accumulation. The objective of this study was to determine if a wetland concentrated (129)I emanating from a former waste disposal basin located on the Savannah River Site (SRS) in South Carolina, USA. Additionally, studies were conducted to evaluate the role of sediment organic matter in immobilizing the radioiodine. Groundwater samples were collected along a 0.7-km transect away from the seepage basin and in the downstream wetlands. The samples were analyzed for (129)I speciation (iodide (I(-)), iodate (IO3(-)), and organo-I). Groundwater (129)I concentrations in many locations in the wetlands (as high as 59.9 Bq L(-1)(129)I) were greatly elevated with respect to the source term (5.9 Bq L(-1)(129)I). (129)I concentration profiles in sediment cores were closely correlated to organic matter concentrations (r(2) = 0.992; n = 5). While the sediment organic matter promoted the uptake of (129)I to the wetland sediment, it also promoted the formation of a soluble organic fraction: 74% of the wetland groundwater (129)I could pass through a 1 kDa (<1 nm) membrane and only 26% of the (129)I was colloidal. Of that fraction that could pass through a 1 kDa membrane, 39% of the (129)I was organo-I. Therefore, while wetlands may be highly effective at immobilizing aqueous (129)I, they may also promote the formation of a low-molecular-weight organic species that does not partition to sediments. This study provides a rare example of radioactivity concentrations increasing rather than decreasing as it migrates from a point source and brings into question assumptions in risk models regarding continuous dilution of released contaminants.
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Relocation Remembered: Perspectives on Senior Transitions in the Living Environment.
Gerontologist
PUBLISHED: 07-09-2013
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The experience of aging may necessitate transitions in living environments, either through adaptations to current residences or through relocations to more supportive environments. For over a half century, the study of these transitions has informed the work of researchers, health and mental health providers, policymakers, and municipal planners. In the 1970s and 80s, knowledge about these transitions advanced through Lawton and Nahemows ecological theory of competence and environmental press, Wisemans behavioral model of relocation decision making, and Litwak and Longinos developmental perspective on senior migrations. This article revisits influential theoretical frameworks that contribute to our understanding of senior transitions in living environments. These seminal works are shown to inform recent studies of relocation and gerontology. This article concludes with a call for a view on housing transitions that reflects the contemporary context.
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Pu(V) transport through Savannah River Site soils - an evaluation of a conceptual model of surface-mediated reduction to Pu(IV).
J Environ Radioact
PUBLISHED: 07-04-2013
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Over the last fifteen years the Savannah River Site (SRS) in South Carolina, USA, was selected as the site of three new plutonium facilities: the Mixed Oxide Fuel Fabrication Facility, Pit Disassembly and Conversion Facility, and the Pu Immobilization Plant. In order to assess the potential human and environmental risk associated with these recent initiatives, improved understanding of the fate and transport of Pu in the SRS subsurface environment is necessary. The hypothesis of this study was that the more mobile forms of Pu, Pu(V) and Pu(VI), would be reduced to the less mobile Pu(III/IV) oxidation states under ambient SRS subsurface conditions. Laboratory-scale dynamic flow experiments (i.e., column studies) indicated that Pu(V) was very mobile in SRS sediments. At higher pH values the mobility of Pu decreased and the fraction of Pu that became irreversibly sorbed to the sediment increased, albeit, only slightly. Conversely, these column experiments showed that Pu(IV) was essentially immobile and was largely irreversibly sorbed to the sediment. More than 100 batch sorption experiments were also conducted with four end-member sediments, i.e., sediments that include the chemical, textural, and mineralogical properties likely to exist in the SRS. These tests were conducted as a function of initial Pu oxidation state, pH, and contact time and consistently demonstrated that although Pu(V) sorbed initially quite weakly to sediments, it slowly, over the course of <33 days, sorbed very strongly to sediments, to approximately the same degree as Pu(IV). This is consistent with our hypothesis that Pu(V) is reduced to the more strongly sorbing form of Pu, Pu(IV). These studies provide important experimental support for a conceptual geochemical model for dissolved Pu in a highly weathered subsurface environment. That is that, irrespective of the initial oxidation state of the dissolved Pu introduced into a SRS sediment system, Pu(IV) controls the environmental transport within a couple weeks and Pu strongly binds to the sediment, limiting its mobility.
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Retention and chemical speciation of uranium in an oxidized wetland sediment from the Savannah River Site.
J Environ Radioact
PUBLISHED: 06-21-2013
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Uranium speciation and retention mechanisms onto Savannah River Site (SRS) wetland sediments was studied using batch (ad)sorption experiments, sequential extraction, U L3-edge X-ray absorption near-edge structure (XANES) spectroscopy, fluorescence mapping and ?-XANES. Under oxidized conditions, U was highly retained by the SRS wetland sediments. In contrast to other similar but much lower natural organic matter (NOM) sediments, significant sorption of U onto the SRS sediments was observed at pH < 4 and pH > 8. Sequential extraction indicated that the U species were primarily associated with the acid soluble fraction (weak acetic acid extractable) and organic fraction (Na-pyrophosphate extractable). Uranium L3-edge XANES spectra of the U-bound sediments were nearly identical to that of uranyl acetate. Based on fluorescence mapping, U and Fe distributions in the sediment were poorly correlated, U was distributed throughout the sample and did not appear as isolated U mineral phases. The primary oxidation state of U in these oxidized sediments was U(VI), and there was little evidence that the high sorptive capacity of the sediments could be ascribed to abiotic or biotic reduction to the less soluble U(IV) species or to secondary mineral formation. Collectively, this study suggests that U may be strongly bound to wetland sediments, not only under reducing conditions by reductive precipitation, but also under oxidizing conditions through NOM-uranium bonding.
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A new pyrrole synthesis via silver(I)-catalyzed cycloaddition of vinylogous diazoester and nitrile.
Org. Lett.
PUBLISHED: 03-11-2013
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A new synthesis of di- and trisubstituted pyrroles was achieved by treating in situ generated vinylogous diazoesters and readily available nitriles with a catalytic amount of silver(I) antimony hexafluoride at room temperature. This method showcased the potential of utilizing silver(I) carbenoids in preparing heterocyclic compounds.
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Regulation of ribosome biogenesis by nucleostemin 3 promotes local and systemic growth in Drosophila.
Genetics
PUBLISHED: 02-22-2013
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Nucleostemin 3 (NS3) is an evolutionarily conserved protein with profound roles in cell growth and viability. Here we analyze cell-autonomous and non-cell-autonomous growth control roles of NS3 in Drosophila and demonstrate its GTPase activity using genetic and biochemical assays. Two null alleles of ns3, and RNAi, demonstrate the necessity of NS3 for cell autonomous growth. A hypomorphic allele highlights the hypersensitivity of neurons to lowered NS3 function. We propose that NS3 is the functional ortholog of yeast and human Lsg1, which promotes release of the nuclear export adapter from the large ribosomal subunit. Release of the adapter and its recycling to the nucleus are essential for sustained production of ribosomes. The ribosome biogenesis role of NS3 is essential for proper rates of translation in all tissues and is necessary for functions of growth-promoting neurons.
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Cdc45 protein-single-stranded DNA interaction is important for stalling the helicase during replication stress.
J. Biol. Chem.
PUBLISHED: 02-04-2013
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Replicative polymerase stalling is coordinated with replicative helicase stalling in eukaryotes, but the mechanism underlying this coordination is not known. Cdc45 activates the Mcm2-7 helicase. We report here that Cdc45 from budding yeast binds tightly to long (? 40 nucleotides) genomic single-stranded DNA (ssDNA) and that 60mer ssDNA specifically disrupts the interaction between Cdc45 and Mcm2-7. We identified a mutant of Cdc45 that does not bind to ssDNA. When this mutant of cdc45 is expressed in budding yeast cells exposed to hydroxyurea, cell growth is severely inhibited, and excess RPA accumulates at or near an origin. Chromatin immunoprecipitation suggests that helicase movement is uncoupled from polymerase movement for mutant cells exposed to hydroxyurea. These data suggest that Cdc45-ssDNA interaction is important for stalling the helicase during replication stress.
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The transformative potential of social works evolving practice in dementia care.
J Gerontol Soc Work
PUBLISHED: 01-29-2013
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Social workers in diverse service systems throughout the United States encounter many opportunities for improving quality of life for people with dementia and their families. Yet practice with this population is unclearly defined and a core set of competencies for such practice does not yet exist. Instead, it is shaped by roles within aging and health systems. These roles are informed by a biomedical disease model of dementia. This article examines social work practice and its connection to evolving views on aging and senility throughout the 20th century. New directions for practice are recommended to improve services for individuals with dementia.
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Novel molecular-level evidence of iodine binding to natural organic matter from Fourier transform ion cyclotron resonance mass spectrometry.
Sci. Total Environ.
PUBLISHED: 01-21-2013
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Major fractions of radioiodine ((129)I) are associated with natural organic matter (NOM) in the groundwater and surface soils of the Savannah River Site (SRS). Electrospray ionization coupled to Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) was applied to elucidate the interactions between inorganic iodine species (iodide and iodate) and a fulvic acid (FA) extracted from a SRS surface soil. Iodate is likely reduced to reactive iodine species by the lignin- and tannin-like compounds or the carboxylic-rich alicyclic molecules (CRAM), during which condensed aromatics and lignin-like compounds were generated. Iodide is catalytically oxidized into reactive iodine species by peroxides, while FA is oxidized by peroxides into more aliphatic and less aromatic compounds. Only 9% of the total identified organo-iodine compounds derived from molecules originally present in the FA, whereas most were iodine binding to newly-produced compounds. The resulting iodinated molecules were distributed in three regions in the van Krevelen diagrams, denoting unsaturated hydrocarbons, lignin and protein. Moreover, characteristics of these organo-iodine compounds, such as their relatively low O/C ratios (<0.2 or <0.4) and yet some degree of un-saturation close to that of lignin, have multiple important environmental implications concerning possibly less sterically-hindered aromatic ring system for iodine to get access to and a lower hydrophilicity of the molecules thus to retard their migration in the natural aquatic systems. Lastly, ~69% of the identified organo-iodine species contains nitrogen, which is presumably present as NH2 or HNCOR groups and a ring-activating functionality to favor the electrophilic substitution. The ESI-FTICR-MS technique provides novel evidence to better understand the reactivity and scavenging properties of NOM towards radioiodine and possible influence of NOM on (129)I migration.
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The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses.
Nat. Immunol.
PUBLISHED: 01-08-2013
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Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T helper type 2 (TH2), but not TH1, allergic responses in both the skin and lungs. Loss of STAT5 in DCs led to the inability to respond to thymic stromal lymphopoietin (TSLP). STAT5 was required for TSLP-dependent DC activation, including upregulation of the expression of costimulatory molecules and chemokine production. Furthermore, TH2 responses in mice with DC-specific loss of STAT5 resembled those seen in mice deficient in the receptor for TSLP. Our results show that the TSLP-STAT5 axis in DCs is a critical component for the promotion of type 2 immunity at barrier surfaces.
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Single-molecule and bulk approaches to the DnaB replication fork helicase.
Front Biosci (Landmark Ed)
PUBLISHED: 01-02-2013
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Motor proteins are enzymes that accomplish mechanical work in a wide variety of biological processes. In this review we focus on bulk and single molecule methods to study how motor proteins function. We discuss in detail the analysis of the motor protein DnaB, a hexameric helicase that unwinds DNA at a replication fork in Gram-negative bacteria. Bulk and single-molecule studies have complemented one another to arrive at a comprehensive mechanistic view of how DnaB unwinds double-stranded DNA.
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Sequestration and remobilization of radioiodine (129I) by soil organic matter and possible consequences of the remedial action at Savannah River Site.
Environ. Sci. Technol.
PUBLISHED: 11-10-2011
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In order to investigate the distributions and speciation of (129)I (and (127)I) in a contaminated F-Area groundwater plume of the Savannah River Site that cannot be explained by simple transport models, soil resuspension experiments simulating surface runoff or stormflow and erosion events were conducted. Results showed that 72-77% of the newly introduced I(-) or IO(3)(-) were irreversibly sequestered into the organic-rich riparian soil, while the rest was transformed by the soil into colloidal and truly dissolved organo-iodine, resulting in (129)I remobilization from the soil greatly exceeding the 1 pCi/L drinking water permit. This contradicts the conventional view that only considers I(-) or IO(3)(-) as the mobile forms. Laboratory iodination experiments indicate that iodine likely covalently binds to aromatic structures of the soil organic matter (SOM). Under very acidic conditions, abiotic iodination of SOM was predominant, whereas under less acidic conditions (pH ?5), microbial enzymatically assisted iodination of SOM was predominant. The organic-rich soil in the vadose zone of F-Area thus acts primarily as a "sink," but may also behave as a potentially important vector for mobile radioiodine in an on-off carrying mechanism. Generally the riparian zone provides as a natural attenuation zone that greatly reduces radioiodine release.
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Enabling association of the GINS protein tetramer with the mini chromosome maintenance (Mcm)2-7 protein complex by phosphorylated Sld2 protein and single-stranded origin DNA.
J. Biol. Chem.
PUBLISHED: 08-24-2011
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The Cdc45-Mcm2-7-GINS (CMG) complex is the replication fork helicase in eukaryotes. Synthetic lethal with Dpb11-1 (Sld2) is required for the initiation of DNA replication, and the S phase cyclin-dependent kinase (S-CDK) phosphorylates Sld2 in vivo. We purified components of the replication initiation machinery and studied their interactions in vitro. We found that unphosphorylated or CDK-phosphorylated Sld2 binds to the mini chromosome maintenance (Mcm)2-7 complex with similar efficiency. Sld2 interaction with Mcm2-7 blocks the interaction between GINS and Mcm2-7. The interaction between CDK-phosphorylated Sld2 and Mcm2-7 is substantially inhibited by origin single-stranded DNA (ssDNA). Furthermore, origin ssDNA allows GINS to bind to Mcm2-7 in the presence of CDK-phosphorylated Sld2. However, unphosphorylated Sld2 blocks the interaction between GINS and Mcm2-7 even in the presence of origin ssDNA. We identified a mutant of Sld2 that does not bind to DNA. When this mutant is expressed in yeast cells, cell growth is severely inhibited with very slow progression into S phase. We propose a model wherein Sld2 blocks the interaction between GINS and Mcm2-7 in vivo. Once origin ssDNA is extruded from the Mcm2-7 ring and CDK phosphorylates Sld2, the origin ssDNA binds to CDK-phosphorylated Sld2. This event may allow the interaction between GINS and Mcm2-7 in vivo. Thus, CDK phosphorylation of Sld2 may be important to release Sld2 from Mcm2-7, thereby allowing GINS to bind Mcm2-7. Furthermore, origin ssDNA may stimulate the formation of the CMG complex by alleviating inhibitory interactions between Sld2 with Mcm2-7.
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Langerhans cells are not required for epidermal Vgamma3 T cell homeostasis and function.
J. Leukoc. Biol.
PUBLISHED: 04-12-2011
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This study tested the hypothesis that V?3 TCR-bearing T cells are influenced by LCs. V?3 T cells and LCs are located in the epidermis of mice. V?3 T cells represent the main T cell population in the skin epithelium and play a crucial role in maintaining the skin integrity, whereas LCs are professional APCs. Although V?3 T cells and LCs form an interdigitating network in the epidermis, not much is known about their reciprocal influence and/or interdependence. We used two different LC-deficient mouse models, in which LCs are constitutively or inducibly depleted, to investigate the role of LCs in maturation, homeostasis, and function of V?3 T cells. We show that V?3 T cell numbers are unaltered by LC deficiency, and V?3 T cells isolated from LC-deficient mice are phenotypically and upon in vitro stimulation, functionally indistinguishable from V?3 T cells isolated from WT mice based on their cytotoxic potential and cytokine production. Additionally, in vivo skin-wounding experiments show no major difference in response of V?3 T cells to wounding in the absence or presence of LCs. These observations indicate that V?3 T cells develop and function independently of LCs.
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The influence of epidural anesthesia on the hearing system after normal labor.
Int J Audiol
PUBLISHED: 04-12-2011
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The purpose of our study was to evaluate the influence of epidural anesthesia on the hearing system in women undergoing normal labor.
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Origin single-stranded DNA releases Sld3 protein from the Mcm2-7 complex, allowing the GINS tetramer to bind the Mcm2-7 complex.
J. Biol. Chem.
PUBLISHED: 04-01-2011
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The replication fork helicase in eukaryotic cells is comprised of Cdc45, Mcm2-7, and GINS (CMG complex). In budding yeast, Sld3, Sld2, and Dpb11 are required for the initiation of DNA replication, but Sld3 and Dpb11 do not travel with the replication fork. Sld3 and Cdc45 bind to early replication origins during the G(1) phase of the cell cycle, whereas Sld2, GINS, polymerase ?, and Dpb11 form a transient preloading complex that associates with origins during S phase. We show here that Sld3 binds tightly to origin single-stranded DNA (ssDNA). CDK-phosphorylated Sld3 binds to origin ssDNA with similar high affinity. Origin ssDNA does not disrupt the interaction between Sld3 and Dpb11, and origin ssDNA does not disrupt the interaction between Sld3 and Cdc45. However, origin ssDNA substantially disrupts the interaction between Sld3 and Mcm2-7. GINS and Sld3 compete with one another for binding to Mcm2-7. However, in a mixture of Sld3, GINS, and Mcm2-7, origin ssDNA inhibits the interaction between Sld3 and Mcm2-7, whereas origin ssDNA promotes the association between GINS and Mcm2-7. We also show that origin single-stranded DNA promotes the formation of the CMG complex. We conclude that origin single-stranded DNA releases Sld3 from Mcm2-7, allowing GINS to bind Mcm2-7.
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GINS and Sld3 compete with one another for Mcm2-7 and Cdc45 binding.
J. Biol. Chem.
PUBLISHED: 03-01-2011
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Sld3 is essential for the initiation of DNA replication, but Sld3 does not travel with a replication fork. GINS binds to Cdc45 and Mcm2-7 to form the replication fork helicase in eukaryotes. We purified Sld3, Cdc45, GINS, and Mcm2-7 and studied their interaction and assembly into complexes. Sld3 binds tightly to Cdc45 in the presence or absence of cyclin-dependent kinase activity. Furthermore, Sld3 binds tightly to the Mcm2-7 complex, and a ternary complex forms among Cdc45, Mcm2-7, and Sld3, with a 1:1:1 stoichiometry (CMS complex). GINS binds directly to Mcm2-7, and GINS competes with Sld3 for Mcm2-7 binding. GINS also binds directly to Cdc45, and GINS competes with Sld3 for Cdc45 binding. Cdc45, Mcm2-7, and GINS form a ternary complex with a stoichiometry of 1:1:1 (CMG complex). Size exclusion data reveal that when Sld3, Cdc45, Mcm2-7, and GINS are added together, the result is a mixture of CMS and CMG complexes. The data suggest that GINS and Sld3 compete with one another for Mcm2-7 and Cdc45 binding. Our results are consistent with a model wherein GINS trades places with Sld3 at a replication origin, contributing to the activation of the replication fork helicase.
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Protective T cell immunity in mice following protein-TLR7/8 agonist-conjugate immunization requires aggregation, type I IFN, and multiple DC subsets.
J. Clin. Invest.
PUBLISHED: 02-16-2011
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The success of a non-live vaccine requires improved formulation and adjuvant selection to generate robust T cell immunity following immunization. Here, using protein linked to a TLR7/8 agonist (conjugate vaccine), we investigated the functional properties of vaccine formulation, the cytokines, and the DC subsets required to induce protective multifunctional T cell immunity in vivo. The conjugate vaccine required aggregation of the protein to elicit potent Th1 CD4+ and CD8+ T cell responses. Remarkably, the conjugate vaccine, through aggregation of the protein and activation of TLR7 in vivo, led to an influx of migratory DCs to the LN and increased antigen uptake by several resident and migratory DC subsets, with the latter effect strongly influenced by vaccine-induced type I IFN. Ex vivo migratory CD8-DEC205+CD103-CD326- langerin-negative dermal DCs were as potent in cross-presenting antigen to naive CD8+ T cells as CD11c+CD8+ DCs. Moreover, these cells also influenced Th1 CD4+ T cell priming. In summary, we propose a model in which broad-based T cell-mediated responses upon vaccination can be maximized by codelivery of aggregated protein and TLR7/8 agonist, which together promote optimal antigen acquisition and presentation by multiple DC subsets in the context of critical proinflammatory cytokines.
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Factors controlling mobility of 127I and 129I species in an acidic groundwater plume at the Savannah River Site.
Sci. Total Environ.
PUBLISHED: 02-15-2011
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In order to quantify changes in iodine speciation and to assess factors controlling the distribution and mobility of iodine at an iodine-129 ((129)I) contaminated site located at the U.S. Department of Energys Savannah River Site (SRS), spatial distributions and transformation of (129)I and stable iodine ((127)I) species in groundwater were investigated along a gradient in redox potential (654 to 360 mV), organic carbon concentration (5 to 60 ?mol L(-1)), and pH (pH 3.2 to 6.8). Total (129)I concentration in groundwater was 8.6±2.8 Bq L(-1) immediately downstream of a former waste seepage basin (well FSB-95DR), and decreased with distance from the seepage basin. (127)I concentration decreased similarly to that of (129)I. Elevated concentrations of (127)I or (129)I were not detected in groundwater collected from wells located outside of the mixed waste plume of this area. At FSB-95DR, the majority (55-86%) of iodine existed as iodide for both (127)I and (129)I. Then, as the iodide move down gradient, some of it transformed into iodate and organo-iodine. Considering that iodate has a higher K(d) value than iodide, we hypothesize that the production of iodate in groundwater resulted in the removal of iodine from the groundwater and consequently decreased concentrations of (127)I and (129)I in downstream areas. Significant amounts of organo-iodine species (30-82% of the total iodine) were also observed at upstream wells, including those outside the mixed waste plume. Concentrations of groundwater iodide decreased at a faster rate than organo-iodine along the transect from the seepage basin. We concluded that removal of iodine from the groundwater through the formation of high molecular weight organo-iodine species is complicated by the release of other more mobile organo-iodine species in the groundwater.
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Iodide accumulation by aerobic bacteria isolated from subsurface sediments of a 129I-contaminated aquifer at the Savannah River site, South Carolina.
Appl. Environ. Microbiol.
PUBLISHED: 01-28-2011
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(129)I is of major concern because of its mobility in the environment, excessive inventory, toxicity (it accumulates in the thyroid), and long half-life (?16 million years). The aim of this study was to determine if bacteria from a (129)I-contaminated oxic aquifer at the F area of the U.S. Department of Energys Savannah River Site, SC, could accumulate iodide at environmentally relevant concentrations (0.1 ?M I(-)). Iodide accumulation capability was found in 3 out of 136 aerobic bacterial strains isolated from the F area that were closely related to Streptomyces/Kitasatospora spp., Bacillus mycoides, and Ralstonia/Cupriavidus spp. Two previously described iodide-accumulating marine strains, a Flexibacter aggregans strain and an Arenibacter troitsensis strain, accumulated 2 to 50% total iodide (0.1 ?M), whereas the F-area strains accumulated just 0.2 to 2.0%. Iodide accumulation by FA-30 was stimulated by the addition of H(2)O(2), was not inhibited by chloride ions (27 mM), did not exhibit substrate saturation kinetics with regard to I(-) concentration (up to 10 ?M I(-)), and increased at pH values of <6. Overall, the data indicate that I(-) accumulation likely results from electrophilic substitution of cellular organic molecules. This study demonstrates that readily culturable, aerobic bacteria of the F-area aquifer do not accumulate significant amounts of iodide; however, this mechanism may contribute to the long-term fate and transport of (129)I and to the biogeochemical cycling of iodine over geologic time.
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Bells palsy during pregnancy: is it associated with adverse perinatal outcome?
Laryngoscope
PUBLISHED: 01-24-2011
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To determine whether an association exists between Bells palsy during pregnancy and adverse perinatal outcomes.
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Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses.
Immunity
PUBLISHED: 01-03-2011
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Skin-resident dendritic cells (DCs) are well positioned to encounter cutaneous pathogens and are required for the initiation of adaptive immune responses. There are at least three subsets of skin DC- Langerhans cells (LC), Langerin(+) dermal DCs (dDCs), and classic dDCs. Whether these subsets have distinct or redundant function in vivo is poorly understood. Using a Candida albicans skin infection model, we have shown that direct presentation of antigen by LC is necessary and sufficient for the generation of antigen-specific T helper-17 (Th17) cells but not for the generation of cytotoxic lymphocytes (CTLs). In contrast, Langerin(+) dDCs are required for the generation of antigen specific CTL and Th1 cells. Langerin(+) dDCs also inhibited the ability of LCs and classic DCs to promote Th17 cell responses. This work demonstrates that skin-resident DC subsets promote distinct and opposing antigen-specific responses.
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Characterization of Langerin-expressing dendritic cell subsets in the normal cornea.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-01-2011
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In addition to Langerhans cells (LCs), other dendritic cells (CD11c(+)) have recently been shown to express Langerin (c-type lectin). In skin, (non-LC) Langerin+ dendritic cells initiate adaptive immunity. However, whether such dendritic cells (DC) reside in the cornea, an immune-privileged tissue, is unknown.
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Rehabilitation with neuromuscular electrical stimulation leads to functional gains in ambulation in patients with secondary progressive and primary progressive multiple sclerosis: a case series report.
J Altern Complement Med
PUBLISHED: 12-09-2010
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Gait disability in patients with secondary progressive multiple sclerosis (SPMS) or primary progressive multiple sclerosis (PPMS) rarely improves.
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Evaluation of a radioiodine plume increasing in concentration at the Savannah River Site.
Environ. Sci. Technol.
PUBLISHED: 12-07-2010
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Field and laboratory studies were carried out to understand the cause for steady increases in (129)I concentrations emanating from radiological basins located on the Savannah River Site, South Carolina. The basins were closed in 1988 by adding limestone and slag and then capping with a low permeability engineered cover. Groundwater (129)I concentrations in a well near the basins in 1993 were 200 pCi L(-1) and are presently between 400 and 1000 pCi L(-1). Iodine speciation in the plume contained wide ranges of iodide, iodate, and organo-iodine concentrations. First-order calculations based on a basin sediment desorption study indicate that the modest increase of 0.7 pH units detected in the study site groundwater over the last 17 years since closure of the basins may be sufficient to produce the observed increased groundwater (129)I concentrations near the basins. Groundwater monitoring of the plume at the basins has shown that the migration of many of the high risk radionuclides originally present at this complex site has been attenuated. However, (129)I continues to leave the source at a rate that may have been exacerbated by the initial remediation efforts. This study underscores the importance of identifying the appropriate in situ stabilization technologies for all source contaminants, especially if their geochemical behaviors differ.
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Sld2 binds to origin single-stranded DNA and stimulates DNA annealing.
Nucleic Acids Res.
PUBLISHED: 11-24-2010
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Sld2 is essential for the initiation of DNA replication, but the mechanism underlying its role in replication is not fully understood. The S-phase cyclin dependent kinase (S-CDK) triggers the association of Sld2 with Dpb11, and a phosphomimetic mutation of Sld2, Sld2T84D, functionally mimics the S-CDK phosphorylated state of Sld2. We report that Sld2T84D binds directly to the single-stranded (ss) DNA of two different origins of replication, and S-CDK phosphorylation of Sld2 stimulates the binding of Sld2 to origin ssDNA. Sld2T84D binds to a thymine-rich ssDNA region of the origin ARS1, and substitution of ARS1 thymines with adenines completely disrupts binding of Sld2T84D. Sld2T84D enhances the ability of origin ssDNA to pulldown Dpb11, and Sld2 binding to origin ssDNA may be important to allow Sld2 and Dpb11 to associate with origin DNA. We also report that Sld2T84D anneals ssDNA of an origin sequence. Dpb11 anneals ssDNA to low levels, and the addition of Sld2T84D with Dpb11 results in higher annealing activity than that of either protein alone. Sld2-stimulated annealing may be important for maintaining genome stability during the initiation of DNA replication.
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Direct mid-infrared femtosecond pulse shaping with a calomel acousto-optic programmable dispersive filter.
Opt Lett
PUBLISHED: 11-03-2010
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Direct amplitude and phase shaping of mid-infrared femtosecond pulses is realized with a calomel-based acousto-optic programmable dispersive filter transparent between 0.4 and 20 ?m. The shaped pulse electric field is fully characterized with high accuracy, using chirped-pulse upconversion and time-encoded arrangement spectral phase interferometry for direct electric field reconstruction techniques. Complex mid-infrared pulse shapes at a center wavelength of 4.9 ?m are generated with a spectral resolution of 14 cm(-1), which exceeds by a factor of 5 the reported experimental resolutions of calomel-based filters.
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Langerhans cells are not required for graft-versus-host disease.
Blood
PUBLISHED: 10-13-2010
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Graft-versus-host disease (GVHD) is initiated and maintained by antigen-presenting cells (APCs) that prime alloreactive donor T cells. APCs are therefore attractive targets for GVHD prevention and treatment. APCs are diverse in phenotype and function, making understanding how APC subsets contribute to GVHD necessary for the development of APC-targeted therapies. Langerhans cells (LCs) have been shown to be sufficient to initiate skin GVHD in a major histocompatibility complex-mismatched model; however, their role when other host APC subsets are intact is unknown. To address this question, we used mice genetically engineered to be deficient in LCs by virtue of expression of diphtheria toxin A under the control of a BAC (bacterial artificial chromosome) transgenic hu-man Langerin locus. Neither CD8- nor CD4-mediated GVHD was diminished in recipients lacking LCs. Similarly, CD8- and CD4-mediated GVHD, including that in the skin, was unaffected if bone marrow came from donors that could not generate LCs, even though donor LCs engrafted in control mice. Engraftment of donor LCs after irradiation in wild-type hosts required donor T cells, with immunofluorescence revealing patches of donor and residual host LCs. Surprisingly, donor LC engraftment in Langerin-diphtheria toxin A (DTA) transgenic hosts was independent of donor T cells, suggesting that a Langerin(+) cell regulates repopulation of the LC compartment.
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Perspective: Whither the problem list? Organ-based documentation and deficient synthesis by medical trainees.
Acad Med
PUBLISHED: 10-01-2010
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The author argues that the well-formulated problem list is essential for both organizing and evaluating diagnostic thinking. He considers evidence of deficiencies in problem lists in the medical record. He observes a trend among medical trainees toward organizing notes in the medical record according to lists of organ systems or medical subspecialties and hypothesizes that system-based documentation may undermine the art of problem formulation and diagnostic synthesis. Citing research linking more sophisticated problem representation with diagnostic success, he suggests that documentation style and clinical reasoning are closely connected and that organ-based documentation may predispose trainees to several varieties of cognitive diagnostic error and deficient synthesis. These include framing error, premature or absent closure, failure to integrate related findings, and failure to recognize the level of diagnostic resolution attained for a given problem. He acknowledges the pitfalls of higher-order diagnostic resolution, including the application of labels unsupported by firm evidence, while maintaining that diagnostic resolution as far as evidence permits is essential to both rational care of patients and rigorous education of learners. He proposes further research, including comparison of diagnostic efficiency between organ- and problem-oriented thinkers. He hypothesizes that the subspecialty-based structure of academic medical services helps perpetuate organ-system-based thinking, and calls on clinical educators to renew their emphasis on the formulation and documentation of complete and precise problem lists and progressively refined diagnoses by trainees.
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Acute ablation of Langerhans cells enhances skin immune responses.
J. Immunol.
PUBLISHED: 09-20-2010
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Understanding the function of Langerhans cells (LCs) in vivo has been complicated by conflicting results from LC-deficient mice. Human Langerin-DTA mice constitutively lack LCs and develop exaggerated contact hypersensitivity (CHS) responses. Murine Langerin-diphtheria toxin receptor (DTR) mice allow for the inducible elimination of LCs and Langerin(+) dermal dendritic cells (dDCs) after administration of diphtheria toxin, which results in reduced CHS. When Langerin(+) dDCs have partially repopulated the skin but LCs are still absent, CHS returns to normal. Thus, LCs appear to be suppressive in human Langerin-DTA mice and redundant in murine Langerin-DTR mice. To determine whether inducible versus constitutive LC ablation explains these results, we engineered human Langerin-DTR mice in which diphtheria toxin ablates LCs without affecting Langerin(+) dDCs. The inducible ablation of LCs in human Langerin-DTR mice resulted in increased CHS. Thus, LC-mediated suppression does not require their absence during ontogeny or during the steady-state and is consistent with a model in which LCs actively suppress Ag-specific CHS responses.
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Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage.
Immunity
PUBLISHED: 07-09-2010
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Dendritic cells (DCs) initiate and control the adaptive immune response against infections. However, their contributions to the anti-self adaptive immune response in autoimmune disorders like systemic lupus erythematosus are uncertain. By constitutively deleting DCs in MRL.Fas(lpr) mice, we show that they have complex roles in murine lupus. The net effect of DC deletion was to ameliorate disease. DCs were crucial for the expansion and differentiation of T cells but, surprisingly, not required for their initial activation. Correspondingly, kidney interstitial infiltrates developed in the absence of DCs, but failed to progress. DC deletion concomitantly decreased inflammatory and regulatory T cell numbers. Unexpectedly, plasmablast numbers and autoantibody concentrations depended on DCs, in contrast to total serum immunoglobulin concentrations, suggesting an effect of DCs on extrafollicular humoral responses. These findings reveal that DCs operate in unanticipated ways in murine lupus and validate them as a potential therapeutic target in autoimmunity.
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In vivo function of Langerhans cells and dermal dendritic cells.
Trends Immunol.
PUBLISHED: 07-01-2010
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In the past few years there has been an explosion in the characterization of skin-resident dendritic cells (DCs). This is largely because of the development of several lines of mice with genetic alterations that allow for selective targeting of many of these subsets. There are now considerable data derived from in vivo experiments using these mice. This review focuses on the relative contribution of murine skin-resident DCs in the generation of immune responses to epicutaneous application of ovalbumin and during contact hypersensitivity. We describe a model in which the two best-characterized skin-resident DCs, langerhans cells (LCs) and Langerin(+) dermal DCs (dDCs) have distinct functions: Langerin(+) dDCs initiate and LCs suppress T cell responses.
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Intravital staining with methylene blue in tympanoplasty.
Eur Arch Otorhinolaryngol
PUBLISHED: 06-19-2010
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Objective of the study is to investigate usefulness of the methylene blue staining for the operation of tympanoplasty in surgical training process with randomized, controlled trial. Two hospitals were involved: Department of Otolaryngology, Assaf Harofeh Medical Center, and Department of Otolaryngology Head and Neck Surgery, Soroka University Medical Center. Tympanoplasty with graft placement was performed by young surgeons on 30 patients (30 ears) with anterior perforations using intraoperative staining of tympanoplasty grafts with methylene blue (Group 1). The same number of patients/ears was operated by the young surgeons without intraoperative staining (Group 2). 76 patients operated without staining by experienced surgeons served as a control group. Results showed tympanic membrane healing (graft take) in 30 (100%) cases in Group 1 and in 26 (86.66%) cases in Group 2. The pure-tone audiogram testing revealed significant improvement of hearing in all successful cases (p < 0.05). No side immediate or postponed effects were detected. We conclude that intravital staining with methylene blue in tympanoplasty simplifies the operation and could assist in better visualization and proper placement of the graft. This technique could be most useful in a training process for resident surgeons.
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Pediatric cochlear implants in prelingual deafness: medium and long-term outcomes.
Isr. Med. Assoc. J.
PUBLISHED: 06-17-2010
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Unfortunately, no large-scale, well-designed, comprehensive studies on medium and long-term effect of cochlear implants in prelingual children exist. Furthermore, the few studies listed have addressed different aspects of this issue, in a non-standardized manner. With the question of outcomes becoming so important in modern medicine, standardized reporting methods are essential. This would enable a fair comparison between the different commercial devices and between rehabilitation-education methods. The studies presented above were published between 1999 and 2008. Due to the long follow-up period required for reporting medium and long-term outcomes, they actually represent patients implanted one and two decades ago. At present and in the near future, we may expect better results from patients who were implanted in the last few years for several reasons: a) superior cochlear implants with better coding strategies; b) developments in rehabilitation and higher awareness among parents and staff; c) better health care and universal screening programs, leading to implants being performed in an earlier age; and d) a high rate of performing bilateral cochlear implants (either simultaneously or sequentially) in the last decade, which accomplishes even better results compared to unilateral implants. From the studies reviewed above, mainstreaming the child who has auditory-verbal and oral communication is the preferred educational setting for maximizing the medium and long-term benefit from a cochlear implant. Hearing and speech skills continue to improve many years after the implant. Non-use and failure rates (as reported by the authors from the medical centers and not solely by the cochlear implant manufacturers) are low, ranging from 1% to 2.7% per year. Overall, patients have a high rate of employment, close to that of the general population. However, they may be less satisfied, as the individual and the parents may feel compromised by their communication skills.
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Distributions of radionuclide sorption coefficients (Kd) in sub-surface sediments and the implications for transport calculations.
J Environ Radioact
PUBLISHED: 04-27-2010
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The effect of the spatial variability of K(d) on calculations of contaminant travel time in the vadose zone was determined. Depth discrete measurements of K(d) were made for a suite of radionuclides ((109)Cd, (57)Co, (60)Co, (85)Sr, (137)Cs, and (88)Y) utilizing a sediment core from the E-Area at the Savannah River Site. The K(d)s were ordered as (85)Sr(2+) < (137)Cs(+) < (109)Cd(2+) < (57)Co(2+) = (60)Co(2+) < (88)Y(3+) and the values generally fell below or near the lowest quartile of values reported in the literature. Correlations were generally weak between soil properties and K(d) values. Most importantly, all of the K(d) distributions could be reasonably approximated as log-normal. Deterministic and stochastic calculations of contaminant travel time to the water table were made. The deterministic calculations were based on each of three conceptual models of the vadose zone: complete stratification (17 strata, each with a different K(d)), two strata (two sections of the vadose zone, each characterized by a single, average K(d)), and unstratified (a single zone with an average K(d)). Stochastic calculations were based on log-normal fits to the K(d) data. The two strata model generally yielded travel times 2x greater than those in the completely stratified model. The unstratified model yielded travel times that were between 3 and 5 times greater than the completely stratified model. The stochastic mean travel times were comparable to those of the two strata model.
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DnaB helicase activity is modulated by DNA geometry and force.
Biophys. J.
PUBLISHED: 03-29-2010
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The replicative helicase for Escherichia coli is DnaB, a hexameric, ring-shaped motor protein that encircles and translocates along ssDNA, unwinding dsDNA in advance of its motion. The microscopic mechanisms of DnaB are unknown; further, prior work has found that DnaBs activity is modified by other replication proteins, indicating some mechanistic flexibility. To investigate these issues, we quantified translocation and unwinding by single DnaB molecules in three tethered DNA geometries held under tension. Our data support the following conclusions: 1), Unwinding by DnaB is enhanced by force-induced destabilization of dsDNA. 2), The magnitude of this stimulation varies with the geometry of the tension applied to the DNA substrate, possibly due to interactions between the helicase and the occluded ssDNA strand. 3), DnaB unwinding and (to a lesser extent) translocation are interrupted by pauses, which are also dependent on force and DNA geometry. 4), DnaB moves slower when a large tension is applied to the helicase-bound strand, indicating that it must perform mechanical work to compact the strand against the applied force. Our results have implications for the molecular mechanisms of translocation and unwinding by DnaB and for the means of modulating DnaB activity.
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The evolving function of Langerhans cells in adaptive skin immunity.
Immunol. Cell Biol.
PUBLISHED: 03-16-2010
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Langerhans cells (LC) are dendritic cell that resides in the epidermis of skin. Paul Langerhans originally observed and named this epinonymous cell more than 140 years ago. Their network-like distribution and dendritic processes that extended up into the stratum corneum convinced him that they represented peripheral nerve cells. It was not determined until almost 100 years later that LC are, in fact, bone marrow-derived and function as skin-resident antigen presenting cells. Many studies have shown that LC are highly immunostimulatory. Recently, data have begun to accumulate suggesting LC have immunoregulatory properties. This review will focus on the participation of LC in the development and regulation of adaptive immune responses.
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Methods to study how replication fork helicases unwind DNA.
Methods Mol. Biol.
PUBLISHED: 03-13-2010
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Replication fork helicases unwind DNA at a replication fork, providing polymerases with single-stranded DNA templates for replication. In bacteria, DnaB unwinds DNA at a replication fork, while in archaeal and eukaryotic organisms the Mcm proteins catalyze replication fork unwinding. Unwinding in archaea is catalyzed by a single Mcm protein that forms multimeric rings, whereas eukaryotic helicase activity is catalyzed by the heterohexameric Mcm2-7 complex acting in concert with Cdc45 and the GINS complex. A subcomplex of eukaryotic Mcm proteins, the Mcm4,6,7 complex, unwinds DNA in vitro, and studies of this assembly reveal insight into the mechanism of the eukaryotic Mcm helicase. Detailed methods for the investigation of replication fork helicase mechanism are described in this chapter. Described herein are methods for the design of DNA substrates for unwinding and branch migration studies, annealing DNA, purifying replication fork helicase proteins, and analyzing DNA unwinding activity.
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[The Hebrew dizziness handicap inventory].
Harefuah
PUBLISHED: 03-10-2010
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The dizziness handicap inventory (DHI) has become a well accepted method for specifically assessing the quality of life among dizzy patients and in evaluating the results of different types of therapy, especially of vestibular rehabilitation programs.
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Magnetic eye tracking: a new approach employing a planar transmitter.
IEEE Trans Biomed Eng
PUBLISHED: 02-17-2010
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A new scleral search coil (SSC) tracking approach employing a planar transmitter has been developed theoretically and tested experimentally. A thin and flat transmitter is much more convenient in installation, operation, and maintenance than the conventional large cubic one. A planar transmitter also increases the mobility of SSC systems, simplifies their accommodation in a limited clinical space, enables bedside testing, and causes no visual distractions and no discomfort to the users. Moreover, it allows tracking not only the SSC orientation, but also its location, which is very important for many medical and scientific applications. The suggested approach provides the speed and precision that are required in SSC applications. The experimental results show that it can be used for the diagnosis of vestibular disorders. The tracking precision is in good agreement with its theoretical estimation.
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Methods to study kinase regulation of the replication fork helicase.
Methods
PUBLISHED: 02-05-2010
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Dbf4-Cdc7 phosphorylation of the Mcm2-7 complex is required for the activation of the replication fork helicase in budding yeast cells. There is a genetic interaction between Dbf4-Cdc7 and Mcm2, and Dbf4-Cdc7 phosphorylates Mcm2 in vitro and in vivo. We initiated a focused study of how Dbf4-Cdc7 phosphorylates Mcm2 in budding yeast, and we also investigated the in vivo implications of this kinase reaction. Described herein are detailed methods for how we conducted biochemical and genetic experiments to dissect the mechanism and function of Dbf4-Cdc7 phosphorylation of Mcm2 in budding yeast cells. The methods are likely applicable to other kinase reactions and studies of replication fork helicases from other organisms.
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Tracking a molecular motor with a nanoscale optical encoder.
Nano Lett.
PUBLISHED: 02-04-2010
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Optical encoders are commonly used in macroscopic machines to make precise measurements of distance and velocity by translating motion into a periodic signal. Here we show how Forster resonance energy transfer can be used to implement this technique at the single-molecule scale. We incorporate a series of acceptor dye molecules into self-assembling DNA, and the periodic signal resulting from unhindered motion of a donor-labeled molecular motor provides nanometer-scale resolution in milliseconds.
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Langerhans cells suppress contact hypersensitivity responses via cognate CD4 interaction and langerhans cell-derived IL-10.
J. Immunol.
PUBLISHED: 10-06-2009
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Mice lacking epidermal Langerhans cells (LC) develop exaggerated contact-hypersensitivity (CHS) responses due to the absence of LC during sensitization/initiation. Examination of T cell responses reveals that the absence of LC leads to increased numbers of hapten-specific CD4 and CD8 T cells but does not alter cytokine expression or development of T regulatory cells. CHS responses and Ag-specific T cells are increased in mice in which MHC class II is ablated specifically in LC suggesting that direct cognate interaction between LC and CD4 cells is required for suppression. LC-derived IL-10 is also required for optimal inhibition of CHS. Both LC-derived IL-10-mediated suppression and full LC activation require LC expression of MHC class II. These data support a model in which cognate interaction of LC with CD4 T cells enables LC to inhibit expansion of Ag-specific responses via elaboration of IL-10.
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Dbf4-Cdc7 phosphorylation of Mcm2 is required for cell growth.
J. Biol. Chem.
PUBLISHED: 08-18-2009
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The Dbf4-Cdc7 kinase (DDK) is required for the activation of the origins of replication, and DDK phosphorylates Mcm2 in vitro. We find that budding yeast Cdc7 alone exists in solution as a weakly active multimer. Dbf4 forms a likely heterodimer with Cdc7, and this species phosphorylates Mcm2 with substantially higher specific activity. Dbf4 alone binds tightly to Mcm2, whereas Cdc7 alone binds weakly to Mcm2, suggesting that Dbf4 recruits Cdc7 to phosphorylate Mcm2. DDK phosphorylates two serine residues of Mcm2 near the N terminus of the protein, Ser-164 and Ser-170. Expression of mcm2-S170A is lethal to yeast cells that lack endogenous MCM2 (mcm2Delta); however, this lethality is rescued in cells harboring the DDK bypass mutant mcm5-bob1. We conclude that DDK phosphorylation of Mcm2 is required for cell growth.
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Source-dependent and source-independent controls on plutonium oxidation state and colloid associations in groundwater.
Environ. Sci. Technol.
PUBLISHED: 04-09-2009
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Plutonium (Pu) was characterized for its isotopic composition, oxidation states, and association with colloids in groundwater samples near disposal basins in F-Area of the Savannah River Site and compared to similar samples collected six years earlier. Two sources of Pu were identified, the disposal basins, which contained a 24Pu/l39Pu isotopic signature consistent with weapons grade Pu, and 244Cm, a cocontaminant that is a progenitor radionuclide of 24Pu. 24Pu that originated primarily from 244Cm tended to be appreciably more oxidized (Pu(V/VI)), less associated with colloids (approximately 1 kDa - 0.2 microm), and more mobile than 239Pu, as suggested by our prior studies at this site. This is not evidence of isotope fractionation but rather "source-dependent" controls on 240Pu speciation which are processes that are not at equilibrium, i.e., processes that appear kinetically hindered. There were also "source-independent" controls on 239Pu speciation, which are those processes that follow thermodynamic equilibrium with their surroundings. For example, a groundwater pH increase in one well from 4.1 in 1998 to 6.1 in 2004 resulted in an order of magnitude decrease in groundwater 239Pu concentrations. Similarly, the fraction of 239Pu in the reduced Pu(III/IV) and colloidal forms increased systematically with decreases in redox condition in 2004 vs 1998. This research demonstrates the importance of source-dependent and source-independent controls on Pu speciation which would impact Pu mobility during changes in hydrological, chemical, or biological conditions on both seasonal and decadal time scales, and over short spatial scales. This implies more dynamic shifts in Pu speciation, colloids association, and transport in groundwater than commonly believed.
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Reducing band slippage in laparoscopic adjustable gastric banding: the mesh plication pars flaccida technique.
Obes Surg
PUBLISHED: 04-02-2009
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Band slippage is a significant complication of laparoscopic adjustable gastric band (LAGB) surgery for the treatment of morbid obesity. This involves prolapse of part of the stomach, with varying degrees of gastric obstruction. The original perigastric technique (PGT) was associated with slippage rates of up to 25%. The pars flaccida technique (PFT) is the more commonly used technique today, reducing slippage rates to as low as 1.4%. We report a technique not previously described, the modified PFT with the use of mesh, and compare slippage rates between these three techniques for band placement.
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Langerhans cell deficiency impairs Ixodes scapularis suppression of Th1 responses in mice.
Infect. Immun.
PUBLISHED: 03-09-2009
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Ixodes scapularis ticks transmit a number of human pathogens, including the Lyme disease spirochete Borrelia burgdorferi. I. scapularis suppresses host immunity in the skin to promote feeding and systemically skew T-helper (Th)-cell differentiation toward Th2 cells in secondary lymphoid organs. Although components of tick saliva are known to influence Th-cell polarization, the mechanism whereby tick feeding in the skin modulates regional and systemic Th-cell responses is unknown. In this study, the role of the epidermal Langerhans cell (LC) subset of skin dendritic cells in tick-mediated Th1/Th2-cell immunomodulation was assessed. Mice deficient in LCs (Langerin-DTA mice) exhibited enhanced lymph node (LN) concanavalin A (ConA)-induced Th1 responses after tick infestation in comparison to results for uninfested Langerin-DTA or wild-type (WT) mice, whereas effects on Th2-cell production of interleukin 4 were more variable. Nonetheless, the altered T-cell response did not impact tick feeding or refeeding. Gamma interferon production by ConA-stimulated LN cells of both WT and LC-deficient mice was enhanced by as much as fourfold after B. burgdorferi-infected-tick feeding, indicating that immunomodulatory effects of tick saliva were not able to attenuate the Th1 immune responses induced by this pathogen. Taken together, these findings show a requirement for LCs in the tick-mediated attenuation of Th1 responses in regional lymph nodes but not in the spleens of mice and show that the presence of a pathogen can overcome the Th1-inhibitory effects of tick feeding on the host.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.