236 research outputs found

    Does Personality Moderate Reciprocity?

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    I completed this experiment in order to better understand how personality moderates reciprocity. Reciprocity is a compliance strategy that involves giving or doing something for someone in exchange for something in return (Cialdini, 1993). I originally predicted that high self-monitors would show greater reciprocity than low self-monitors. Also, I predicted people with high need for cognition will show more reciprocity than people with a low need for cognition. In addition, I hypothesized that people with a low need to evaluate will show more reciprocity than people with a high need to evaluate. Participants were randomly assigned to either a “Soft Sell” Condition, in which reciprocity was not explicitly invoked, a “Hard Sell” Condition, in which reciprocity was explicitly invoked, or a control condition, in which no reciprocity was invoked. Reciprocity was measured by the amount of words that participants used to answer a mundane questionnaire. Although there were the predicted differences in reciprocity between the different personality types, these differences were not significant

    Chelating Ligands and Nanomaterials Based on Graphene Oxide for the Reduction and Sequestration of Radiometals and Protein Purification

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    Nuclear waste remediation and protein purification using immobilized metals can benefit enormously from the design and implementation of novel chelating nanomaterials. Available commercial resins capable of sequestering metals are based on bulk materials such as organic polymers, ceramics, and their composites. The use of two-dimensional nanoplatforms with large surface areas expands the horizon for the research and development of new systems with higher efficiency and lower cost. Fundamental science challenges remain in the synthesis and characterization of these nanomaterials and their integration with known or novel coordinating ligands. Chemical exfoliation of graphite under strong oxidizing conditions yields graphene oxide (GO) nanosheets with oxy functional groups on the carbon basal plane and edges. The structure of GO is still not well understood due to its non-stoichiometric nature and strong dependence on synthetic conditions. Herein, GO was investigated to better understand its mechanism of formation, the nature of its surface functional groups, and its suitability as a reduction and sequestration platform for radiometals and protein purification. It was found that ozonolysis of graphite in the widely-used Hummers’ method, hitherto largely overlooked in the literature, leads to the formation of secondary epoxy and peroxymonosulfate ester functional groups, arising from a rotationally hindered Criegee intermediate and sulfuric acid in a strongly favored thermodynamic process. This mechanistic step is followed by the formation of adjacent epoxy and hydroxy groups as major functionalities on GO via a radical process, and leaves a significant amount of unreacted peroxides above levels previously recognized. The thermal decomposition of GO releases sulfur oxygen species (SO2 and SO), but does not appear to release ozone even if this reaction pathway is moderately favored thermodynamically. A new structural model is proposed for GO based on detailed chemical and spectroscopic data that provides insight into observed chemical reactivity and physical properties, including the antimicrobial activity and protein deactivation. Titanium dioxide (TiO2) is a widely studied semi-conductor photoreductant with applications in water splitting and decomposition of organic compounds. It has been previously demonstrated that TiO2 can reduce the radioactive waste metal 99Tc under UV irradiation. Monodispersed TiO2 anatase nanoparticles were synthesized on the GO surface, showing excellent coverage and strong binding to the carbon basal plane, yielding TiO2/GO nanocomposites (TGO). TGO is characterized by an absorption window shifted to the visible region of the spectrum compared to pristine TiO2. Results show that TGO can reduce up to 40% of 99Tc from its oxidized form pertechnetate (TcO4-) under UV irradiation, but photocatalyzes little reduction of 99Tc under visible light conditions. The chemistry of chelates for radiometals has important impacts on radioactive waste cleanup and radiopharmaceutical design. It is well known that within Group 7 congeners Re and Tc are characterized by similar physical-chemical properties. Thus, natural Re (37.4% 185Re and 62.6% 187Re) is commonly used as a non-radioactive analogue of 99Tc. Further, the radioisotopes 186Re and 188Re are important medical isotopes for radiotherapy. In this investigation, the binding stability of natural Re was compared with that of 188Re using two classes of chelates. Novel compounds with two nitrogen and two sulfur binding sites (N2S2) and known tripeptides with three nitrogen and one sulfur binding sites (N3S) were evaluated. It was shown that 188Re complexed with N3S ligands at tracer levels (≤ nanomolar concentration) proved to be unstable after a few hours, in contrast to previous studies with macroscopic amounts of natural Re which demonstrated greater stability. The N2S2 chelates appeared to stably bind 188Re at tracer levels, indicating a more resilient behavior towards the radiometal at the tracer level compared to N3S chelates. GO has been recently proposed as a support for immobilized metal affinity chromatography (IMAC) resins which are widely used adsorbent materials for protein purification processes. The typical IMAC resin is based on three-dimensional polysaccharide beads containing metal-coordinating ligands. The two-dimensional nature of GO has the potential for minimizing the amount of supporting material with respect to the metal-binding ligands and maximizing the capture of target proteins. Here, four new IMAC resins were synthesized and characterized based on GO and carboxylated GO (CGO) functionalized with mono- and bis-nitriloacetic acid sites (NTA and bis-NTA). The ligand bis-NTA is proposed here for the first time. Morphological, structural, vibrational, and spectroscopic studies were conducted on these IMAC resins revealing their different level of suitability for protein purification applications. Elemental analysis revealed a nickel content as high as 58.6 mg/mL of resin, at least one or two orders of magnitude higher than common commercially available resins (0.35 to 1.06 mg/mL). The GO and CGO-based resins were employed in the purification of e-green fluorescence protein (eGFP) in batch mode. The protein loading was as high as 50.3 mg/mL of resin with the CGO-based bis-NiNTA resins. These results indicated that the increase in nickel content has already translated to an amount of eluted protein at least on par with commercial resins in the purification of eGFP. It should be pointed out that the comparison between performance parameters of 2D-nanomaterials and macroscopic spherical beads is generally underestimated because it does not consider the differences in packing factors and swelling properties. It is expected that future resin optimization of the chemical conditions for protein purification, especially reduction of non-specific binding by use of surfactants, will increase protein loading to levels much superior to commercially available IMAC resins. The possibility of using our IMAC resins in radioisotope waste remediation was also tested. Initial results indicate that CGO, and to a lesser extent GO-NTA and CGO-NTA, can be used to effectively capture reduced 99Tc (63%, 44%, and 37% of control sample, respectively). In this thesis, the following major results were achieved: First, an in-depth characterization of GO and CGO is presented along with their mechanisms of formation. Second, GO was combined with TiO2 to form TGO, a platform for the reduction of 99Tc. Third, the tracer level binding of 188Re by N3S ligands was shown to be much less stable than at macroscopic levels, while it is stable with the N2S2 ligands. Fourth, GO and CGO-based resins with NTA and bis-NTA ligands were synthesized, characterized, and used for the purification of eGFP. The protein loading capacity was at least as high as commercial resins, but was affected by a high non-specific binding. Fifth, CGO exhibited an impressive binding affinity for reduced 99Tc. Overall, GO and CGO based nanomaterials have been shown to have tremendous potential for radiometal reduction and sequestration as well as protein purification

    Users guide for ERB 7 MAT (including the first year quality control)

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    In the first section of this report background information for the use of the ERB-7 Master Archival Tapes (MAT) is provided. The second section gives details regarding the scientific validity and quality of the MAT. The MAT data analyzed covers the period from November 16, 1978 to October 31, 1979

    User's guide: Nimbus-7 Earth radiation budget narrow-field-of-view products. Scene radiance tape products, sorting into angular bins products, and maximum likelihood cloud estimation products

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    The archived Earth radiation budget (ERB) products produced from the Nimbus-7 ERB narrow field-of-view scanner are described. The principal products are broadband outgoing longwave radiation (4.5 to 50 microns), reflected solar radiation (0.2 to 4.8 microns), and the net radiation. Daily and monthly averages are presented on a fixed global equal area (500 sq km), grid for the period May 1979 to May 1980. Two independent algorithms are used to estimate the outgoing fluxes from the observed radiances. The algorithms are described and the results compared. The products are divided into three subsets: the Scene Radiance Tapes (SRT) contain the calibrated radiances; the Sorting into Angular Bins (SAB) tape contains the SAB produced shortwave, longwave, and net radiation products; and the Maximum Likelihood Cloud Estimation (MLCE) tapes contain the MLCE products. The tape formats are described in detail

    Electrophysiological Investigations of Prion Protein Roles in Health and Disease

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    Prion diseases are transmissible and fatal neurological disorders associated with the misfolding of cellular prion protein (PrPC) into disease-causing isoforms (PrPD) in the central nervous system. The diseases have three etiologies; acquired through exposure to the infectious PrPD, sporadic, arising from no known cause, and hereditary due to familial mutations within the PRNP gene. The manifestation of clinical signs is associated with the disruption of neuronal activity and subsequent degeneration of neurons. To generate insight into the mechanisms by which neuronal activity becomes disrupted in prion diseases, electrophysiological techniques have been applied to closely study the electrical signaling properties of neurons that lack functional PrPC as well as neurons that are developing pathological features of prion diseases due to infection or genetic mutation. In this review, we will compile the electrophysiological evidences of neurophysiological roles of PrPC, how those roles are changed in neurons that are developing prion diseases, and how disease-associated effects are exacerbated during the clinical stage of disease

    New preterm infant growth curves influence of gender and race on birth size

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    BackgroundAdequate fetal and postnatal growth is crucial to the health of infants and significant to their future adult health. Preterm infant growth curves are used in the assessment of fetal and postnatal growth. Current growth curves, such as the Lubchenc curves, are limited by older homogenous data sets, smaller sample sizes, varying age ranges, combined-gender curves and/or disparate data sources. Evaluation of these curves was needed to determine whether a new set of curves with updated high-risk percentile classification cutoffs for preterm infants was needed. The presence of birth size differences between genders and racial groups also was important to identify and explore.MethodsIn the first specific aim, smoothed growth curves were created for males and females for weight, length and head circumference using a large data set (Pediatrix Medical Group). The original data included 391,681 infants (56% male; 52% white, 23% Hispanic, 15% black, 10% other) ranging from 22 to 42 weeks gestation. Infants of nonsingleton pregnancies or with ambiguous gender, congenital anomalies or physiologically improbable growth measurements were excluded. The curves were fit to the data using the LMS method. The goodness-of-fit was assessed using worm plots, z-scores, and visual inspection. The curves were validated through the evaluation of z-scores anddistribution of infants between the high-risk percentile-for-age classifications. The new curves were compared to the Lubchenco curves visually, at selected points, and via the percentages of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) infants.The second specific aim investigated size differences between males and females and among racial groups. Gender differences in birth size were compared via ANOVAs, overlaid curves, specific points on the new Pediatrix curves, and distribution of infants between the high-risk percentile-for-age classifications. Racial differences in birth size were compared via ANOVAs, z-score comparisons, distribution of infants between the high-risk percentile-for-age classifications, and odds ratios. Several maternal characteristics were examined to explain the differences found in birth size by racial group (logistic regression). The sickness level of the infants was investigated to help explain group differences.ResultsFor the first specific aim, the new Pediatrix percentiles were found to have smaller measurements than the Lubchenco curves until about 30 weeks, were somewhat similar between about 30 and 36 weeks, and were larger after 36 weeks. Overall the Lubchenco curves misclassified 15% of males and 10% of females as SGA, appropriatefor- gestational age (AGA), or LGA according to the new Pediatrix curves.For the second specific aim, males were found to be significantly larger than females in weight, length, and head circumference. A higher percentage of black infants were born earlier and were significantly smaller than Hispanic and white infants. Relative to the medians, depending on gestational age, the z-scores of black infants placed up to19 percentiles below white infants. At 32-41 weeks, black infants had two to three times the risk of white infants of being born SGA. Controlling for race, preeclampsia/eclampsia was a consistent predictor of SGA for weight, length and head circumference at all age groups and smoking was a predictor for infants born at 32-41 weeks. The prevalence of being sick (APGAR at 1 minute < 3) at birth was greater in black infants and those classified as SGA for weight. Conclusions Accurate preterm growth curves are crucial to the assessment of growth status and therefore are vital to the health of infants. This study found strong evidence for the replacement of the Lubchenco growth curves with contemporary gender-specific curves. This study also found significant differences in birth size (weight, length, and head circumference) between male and female infants and among the racial groups that warrant further investigation.M.S., Human Nutrition -- Drexel University, 200

    Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains

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    Prions propagate as multiple strains in a wide variety of mammalian species. The detection of all such strains by a single ultrasensitive assay such as Real Time Quaking-induced Conversion (RT-QuIC) would facilitate prion disease diagnosis, surveillance and research. Previous studies have shown that bank voles, and transgenic mice expressing bank vole prion protein, are susceptible to most, if not all, types of prions. Here we show that bacterially expressed recombinant bank vole prion protein (residues 23-230) is an effective substrate for the sensitive RT-QuIC detection of all of the different prion types that we have tested so far--a total of 28 from humans, cattle, sheep, cervids and rodents, including several that have previously been undetectable by RT-QuIC or Protein Misfolding Cyclic Amplification. Furthermore, comparison of the relative abilities of different prions to seed positive RT-QuIC reactions with bank vole and not other recombinant prion proteins allowed discrimination of prion strains such as classical and atypical L-type bovine spongiform encephalopathy, classical and atypical Nor98 scrapie in sheep, and sporadic and variant Creutzfeldt-Jakob disease in humans. Comparison of protease-resistant RT-QuIC conversion products also aided strain discrimination and suggested the existence of several distinct classes of prion templates among the many strains tested

    Sporadic Creutzfeldt-Jakob disease infected human cerebral organoids retain the original human brain subtype features following transmission to humanized transgenic mice

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    Human cerebral organoids (COs) are three-dimensional self-organizing cultures of cerebral brain tissue differentiated from induced pluripotent stem cells. We have recently shown that COs are susceptible to infection with different subtypes of Creutzfeldt-Jakob disease (CJD) prions, which in humans cause different manifestations of the disease. The ability to study live human brain tissue infected with different CJD subtypes opens a wide array of possibilities from differentiating mechanisms of cell death and identifying neuronal selective vulnerabilities to testing therapeutics. However, the question remained as to whether the prions generated in the CO model truly represent those in the infecting inoculum. Mouse models expressing human prion protein are commonly used to characterize human prion disease as they reproduce many of the molecular and clinical phenotypes associated with CJD subtypes. We therefore inoculated these mice with COs that had been infected with two CJD subtypes (MV1 and MV2) to see if the original subtype characteristics (referred to as strains once transmitted into a model organism) of the infecting prions were maintained in the COs when compared with the original human brain inocula. We found that disease characteristics caused by the molecular subtype of the disease associated prion protein were similar in mice inoculated with either CO derived material or human brain material, demonstrating that the disease associated prions generated in COs shared strain characteristics with those in humans. As the first and only in vitro model of human neurodegenerative disease that can faithfully reproduce different subtypes of prion disease, these findings support the use of the CO model for investigating human prion diseases and their subtypes

    Regulated internalization of NMDA receptors drives PKD1-mediated suppression of the activity of residual cell-surface NMDA receptors

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    Background Constitutive and regulated internalization of cell surface proteins has been extensively investigated. The regulated internalization has been characterized as a principal mechanism for removing cell-surface receptors from the plasma membrane, and signaling to downstream targets of receptors. However, so far it is still not known whether the functional properties of remaining (non-internalized) receptor/channels may be regulated by internalization of the same class of receptor/channels. The N-methyl-D-aspartate receptor (NMDAR) is a principal subtype of glutamate-gated ion channel and plays key roles in neuronal plasticity and memory functions. NMDARs are well-known to undergo two types of regulated internalization – homologous and heterologous, which can be induced by high NMDA/glycine and DHPG, respectively. In the present work, we investigated effects of regulated NMDAR internalization on the activity of residual cell-surface NMDARs and neuronal functions. Results In electrophysiological experiments we discovered that the regulated internalization of NMDARs not only reduced the number of cell surface NMDARs but also caused an inhibition of the activity of remaining (non-internalized) surface NMDARs. In biochemical experiments we identified that this functional inhibition of remaining surface NMDARs was mediated by increased serine phosphorylation of surface NMDARs, resulting from the activation of protein kinase D1 (PKD1). Knockdown of PKD1 did not affect NMDAR internalization but prevented the phosphorylation and inhibition of remaining surface NMDARs and NMDAR-mediated synaptic functions. Conclusion These data demonstrate a novel concept that regulated internalization of cell surface NMDARs not only reduces the number of NMDARs on the cell surface but also causes an inhibition of the activity of remaining surface NMDARs through intracellular signaling pathway(s). Furthermore, modulating the activity of remaining surface receptors may be an effective approach for treating receptor internalization-induced changes in neuronal functions of the CNS

    Rapid and sensitive RT-QuIC detection of human Creutzfeldt-Jakob disease using cerebrospinal fluid.

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    Fast, definitive diagnosis of Creutzfeldt-Jakob disease (CJD) is important in assessing patient care options and transmission risks. Real-time quaking-induced conversion (RT-QuIC) assays of cerebrospinal fluid (CSF) and nasal-brushing specimens are valuable in distinguishing CJD from non-CJD conditions but have required 2.5 to 5 days. Here, an improved RT-QuIC assay is described which identified positive CSF samples within 4 to 14 h with better analytical sensitivity. Moreover, analysis of 11 CJD patients demonstrated that while 7 were RT-QuIC positive using the previous conditions, 10 were positive using the new assay. In these and further analyses, a total of 46 of 48 CSF samples from sporadic CJD patients were positive, while all 39 non-CJD patients were negative, giving 95.8% diagnostic sensitivity and 100% specificity. This second-generation RT-QuIC assay markedly improved the speed and sensitivity of detecting prion seeds in CSF specimens from CJD patients. This should enhance prospects for rapid and accurate ante mortem CJD diagnosis. IMPORTANCE\u2002: A long-standing problem in dealing with various neurodegenerative protein misfolding diseases is early and accurate diagnosis. This issue is particularly important with human prion diseases, such as CJD, because prions are deadly, transmissible, and unusually resistant to decontamination. The recently developed RT-QuIC test allows for highly sensitive and specific detection of CJD in human cerebrospinal fluid and is being broadly implemented as a key diagnostic tool. However, as currently applied, RT-QuIC takes 2.5 to 5 days and misses 11 to 23% of CJD cases. Now, we have markedly improved RT-QuIC analysis of human CSF such that CJD and non-CJD patients can be discriminated in a matter of hours rather than days with enhanced sensitivity. These improvements should allow for much faster, more accurate, and practical testing for CJD. In broader terms, our study provides a prototype for tests for misfolded protein aggregates that cause many important amyloid diseases, such as Alzheimer's, Parkinson's, and tauopathies
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