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1.
Science ; 378(6617): 246-248, 2022 10 21.
Article En | MEDLINE | ID: mdl-36264815

"Competent outsiders" must be able to evaluate the credibility of science-based arguments.


Communication , Competency-Based Education , Science , Humans , Science/education , Competency-Based Education/standards
2.
J Biol Chem ; 293(18): 6751-6761, 2018 05 04.
Article En | MEDLINE | ID: mdl-29549125

The 14-3-3 family comprises a group of small proteins that are essential, ubiquitous, and highly conserved across eukaryotes. Overexpression of the 14-3-3 proteins σ, ϵ, ζ, and η correlates with high metastatic potential in multiple cancer types. In Dictyostelium, 14-3-3 promotes myosin II turnover in the cell cortex and modulates cortical tension, cell shape, and cytokinesis. In light of the important roles of 14-3-3 proteins across a broad range of eukaryotic species, we sought to determine how 14-3-3 proteins interact with myosin II. Here, conducting in vitro and in vivo studies of both Dictyostelium (one 14-3-3 and one myosin II) and human proteins (seven 14-3-3s and three nonmuscle myosin IIs), we investigated the mechanism by which 14-3-3 proteins regulate myosin II assembly. Using in vitro assembly assays with purified myosin II tail fragments and 14-3-3, we demonstrate that this interaction is direct and phosphorylation-independent. All seven human 14-3-3 proteins also altered assembly of at least one paralog of myosin II. Our findings indicate a mechanism of myosin II assembly regulation that is mechanistically conserved across a billion years of evolution from amebas to humans. We predict that altered 14-3-3 expression in humans inhibits the tumor suppressor myosin II, contributing to the changes in cell mechanics observed in many metastatic cancers.


14-3-3 Proteins/metabolism , Myosin Type II/metabolism , 14-3-3 Proteins/physiology , Animals , Chromatography, Gel , Cytokinesis/physiology , Dictyostelium/metabolism , Humans , Phosphorylation , Protein Binding , Protozoan Proteins/metabolism , Spectrometry, Fluorescence , Surface Plasmon Resonance
3.
Methods Mol Biol ; 1737: 341-350, 2018.
Article En | MEDLINE | ID: mdl-29484602

Bacterial small RNA molecules (sRNAs) are increasingly recognized as central regulators of bacterial stress responses and pathogenesis. In many cases, RNA-binding proteins are critical for the stability and function of sRNAs. Previous studies have adopted strategies to genetically tag an sRNA of interest, allowing isolation of RNA-protein complexes from cells. Here we present a sequence-specific affinity purification protocol that requires no prior genetic manipulation of bacterial cells, allowing isolation of RNA-binding proteins bound to native RNA molecules.


Bacterial Proteins/metabolism , Chromatography, Affinity/methods , Pseudomonas aeruginosa/metabolism , RNA, Bacterial/metabolism , RNA, Small Untranslated/metabolism , RNA-Binding Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/isolation & purification , Binding Sites , Cross-Linking Reagents/metabolism , Protein Binding , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/growth & development , RNA, Bacterial/genetics , RNA, Small Untranslated/genetics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/isolation & purification , Ultraviolet Rays
4.
Public Underst Sci ; 26(5): 596-611, 2017 07.
Article En | MEDLINE | ID: mdl-27340172

Popular media influences ideas about science constructed by the public. To sway media productions, public policy organizations have increasingly promoted use of science consultants. This study contributes to understanding the connection from science consultants to popular media to public outcomes. A science-based television series was examined for intended messages of the creator and consulting scientist, and received messages among middle school and non-science university students. The results suggest the consulting scientist missed an opportunity to influence the portrayal of the cultural contexts of science and that middle school students may be reading these aspects uncritically-a deficiency educators could potentially address. In contrast, all groups discussed the science content and practices of the show, indicating that scientific facts were salient to both media makers and audiences. This suggests popular media may influence the public knowledge of science, supporting concerns of scientists about the accuracy of fictional television and film.


Perception , Public Opinion , Science , Television , Female , Humans , Male , Schools , Students , Universities
5.
Psychiatry Res ; 234(3): 352-61, 2015 Dec 30.
Article En | MEDLINE | ID: mdl-26602610

Although deep grey matter (GM) involvement in multiple sclerosis (MS) is well documented, in-vivo multi-parameter magnetic resonance imaging (MRI) studies and association with detailed cognitive measures are limited. We investigated volumetric, diffusion and perfusion metrics in thalamus, hippocampus, putamen, caudate nucleus and globus pallidum, and neuropsychological measures, spanning 4 cognitive domains, in 60 relapsing-remitting MS patients (RRMS) (mean disease duration of 5.1 years, median EDSS of 1.5) and 30 healthy controls. There was significantly reduced volume of thalamus, hippocampus and putamen in the RRMS patients, but no diffusion or perfusion changes in these structures. Decreased volume in these deep GM volumes in RRMS patients was associated with a modest reduction in cognitive performance, particularly information processing speed, consistent with a subtle disruption of distributed networks, that subserve cognition, in these patients. Future longitudinal studies are needed to elucidate the influence of deep GM changes on the evolution of cognitive deficits in MS.


Brain/pathology , Cognition , Gray Matter/pathology , Magnetic Resonance Imaging/methods , Multiple Sclerosis, Relapsing-Remitting/pathology , Adult , Atrophy/pathology , Case-Control Studies , Caudate Nucleus/pathology , Cognition Disorders/complications , Female , Humans , Male , Middle Aged , Putamen/pathology , Thalamus/pathology
6.
J Appl Meas ; 16(2): 171-92, 2015.
Article En | MEDLINE | ID: mdl-26075666

The latest national science framework has formally stated the need for developing assessments that test both students' content knowledge and scientific practices. In response to this call, a science assessment that consists of (a) content items that measure students' understanding of a grade eight physics topic and (b) argumentation items that measure students' argumentation competency has been developed. This paper investigated the function of these content and argumentation items with a multidimensional measurement framework from two perspectives. First, we performed a dimensionality analysis to investigate whether the relationship between the content and argumentation items conformed to test deign. Second, we conducted a differential item functioning analysis in the multidimensional framework to examine if any content or argumentation item unfairly favored students with an advanced level of English literacy. Methods and findings of this study could inform future research on the validation of assessments measuring higher-order and complex abilities.


Educational Measurement , Models, Statistical , Science/education , Adolescent , Educational Measurement/standards , Educational Measurement/statistics & numerical data , Female , Humans , Male
7.
Sci Educ ; 99(2): 199-237, 2015 03.
Article En | MEDLINE | ID: mdl-28579645

There are widespread policy concerns to improve (widen and increase) science, technology, engineering, and mathematics participation, which remains stratified by ethnicity, gender, and social class. Despite being interested in and highly valuing science, Black students tend to express limited aspirations to careers in science and remain underrepresented in post-16 science courses and careers, a pattern which is not solely explained by attainment. This paper draws on survey data from nationally representative student cohorts and longitudinal interview data collected over 4 years from 10 Black African/Caribbean students and their parents, who were tracked from age 10-14 (Y6-Y9), as part of a larger study on children's science and career aspirations. The paper uses an intersectional analysis of the qualitative data to examine why science careers are less "thinkable" for Black students. A case study is also presented of two young Black women who "bucked the trend" and aspired to science careers. The paper concludes with implications for science education policy and practice.

8.
Microbiologyopen ; 3(6): 950-60, 2014 Dec.
Article En | MEDLINE | ID: mdl-25351924

Small bacterial regulatory RNAs (sRNAs) have gained immense appreciation over the last decade for their roles in mediating posttranscriptional gene regulation of numerous physiological processes. Several proteins contribute to sRNA stability and regulation, most notably the Hfq RNA-binding protein. However, not all sRNAs rely on Hfq for their stability. It is therefore likely that other proteins contribute to the stability and function of certain bacterial sRNAs. Here, we describe a methodology for identifying in vivo-binding proteins of sRNAs, developed using the iron-responsive PrrF and PrrH sRNAs of Pseudomonas aeruginosa. RNA was isolated from iron-depleted cultures, which were irradiated to cross-link nucleoprotein complexes. Subsequently, PrrF- and PrrH-protein complexes were enriched using cDNA "bait", and enriched RNA-protein complexes were analyzed by tandem mass spectrometry to identify PrrF and PrrH associated proteins. This method identified Hfq as a potential PrrF- and PrrH-binding protein. Interestingly, Hfq was identified more often in samples probed with the PrrF cDNA "bait" as compared to the PrrH cDNA "bait", suggesting Hfq has a stronger binding affinity for the PrrF sRNAs in vivo. Hfq binding to the PrrF and PrrH sRNAs was validated by electrophoretic mobility shift assays with purified Hfq protein from P. aeruginosa. As such, this study demonstrates that in vivo cross-linking coupled with sequence-specific affinity chromatography and tandem mass spectrometry (SSAC-MS/MS) is an effective methodology for unbiased identification of bacterial sRNA-binding proteins.


Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Chromatography, Affinity/methods , Mass Spectrometry/methods , Pseudomonas aeruginosa/metabolism , RNA, Bacterial/metabolism , RNA, Small Untranslated/metabolism , Bacterial Proteins/genetics , Protein Binding , Pseudomonas aeruginosa/chemistry , Pseudomonas aeruginosa/genetics , RNA, Bacterial/genetics , RNA, Small Untranslated/genetics
9.
PLoS Biol ; 12(1): e1001760, 2014 Jan.
Article En | MEDLINE | ID: mdl-24453938

Over the last decade macroeconomic studies have established a clear link between student achievement on science and math tests and per capita gross domestic product (GDP) growth, supporting the widely held belief that science, technology, engineering, and math(STEM) education are important factors in the production of economic prosperity. We critique studies that use science and math tests to predict GDP growth, arguing that estimates of the future economic value of STEM education involve substantial speculation because they ignore the impacts of economic growth on biodiversity and ecosystem functionality, which, in the long-term, limit the potential for future economic growth. Furthermore, we argue that such ecological impacts can be enabled by STEM education. Therefore, we contend that the real economic imperative for the STEM pipeline is not just raising standardized test scores, but also empowering students to assess, preserve, and restore ecosystems in order to reduce ecological degradation and increase economic welfare.


Ecology/education , Schools/economics , Students/psychology , Biodiversity , Ecology/ethics , Educational Status , Gross Domestic Product/trends , Humans , United States
10.
Cochlear Implants Int ; 13(3): 181-3, 2012 Aug.
Article En | MEDLINE | ID: mdl-22333040

RELEVANCE: Biofilm forming microorganisms are responsible for the infection of a number of different indwelling medical devices including cochlear implants. The current definitive technique for proving biofilm infection is the use of scanning electron microscopy that is expensive and of limited availability. CLINICAL PRESENTATION: A persistently infected cochlear implant was explanted. At operation it was surrounded by a fibrous capsule containing a glue-like substance, characteristic of biofilm formation that yielded Staphylococcus aureus after ultrasonication of the device. TECHNIQUE: The explanted cochlear implant was placed in a nutrient broth in an ultrasonic water bath. The implant was ultrasonicated for 5 minutes and the broth cultured on blood agar, incubated aerobically and anaerobically for 48 hours, and then incubated in air on Maconkey agar for 24 hours. This produced a heavy, confluent growth of S. aureus, in contrast to previous aspirates from a blister that lay over the infected implant that grew a coliform organism and Pseudomonas sp. CONCLUSION: Ultrasonication is a widely available and relatively inexpensive technique that can be used to improve the recovery of biofilm-associated organisms from explanted cochlear implants.


Biofilms , Cochlear Implants/microbiology , Prosthesis-Related Infections/diagnosis , Sonication , Staphylococcal Infections/diagnosis , Staphylococcus aureus/physiology , Bacteriological Techniques , Chronic Disease , Device Removal , Humans , Male , Middle Aged , Prosthesis-Related Infections/surgery , Pseudomonas Infections/diagnosis , Pseudomonas Infections/surgery , Reoperation , Staphylococcal Infections/surgery , Tomography, X-Ray Computed
12.
BMC Microbiol ; 11: 49, 2011 Mar 04.
Article En | MEDLINE | ID: mdl-21375756

BACKGROUND: The rabbit model is an ideal means to study the pathogenesis of tuberculosis due to its semblance to the disease in humans. We have previously described the results using a bronchoscopic route of infection with live bacilli as a reliable means of generating lung cavities in sensitized rabbits. The role of sensitization in the development of disease outcomes has been well established in several animal models. We have described here the varying gross pathology that result from lack of sensitization with heat-killed M. bovis prior to high-dose bronchoscopic infection with live bacilli. RESULTS: Rabbits lacking sensitization did not generate lung cavities, but instead formed solely a tuberculoid pneumonia that replaced the normal lung parenchyma in the area of infection. Extrapulmonary dissemination was seen in approximately equal frequency and distribution in both rabbit populations. Notable differences include the lack of intestinal lesions in non-sensitized rabbits likely due to the lack of ingestion of expectorated bacilli from cavitary lesions. The experiment also employed a modified scoring system developed initially in the primate model of tuberculosis to allow for the quantification of findings observed at necropsy. CONCLUSIONS: To date, no such scoring system has been employed in the rabbit model to describe gross pathology. The quantitative methodology would allow for rapid comparative analyses and standardization of thoracic and extrapulmonary pathology that could be evaluated for statistical significance. The aim is to use such a scoring system as the foundation for all future rabbit studies describing gross pathology at all stages in TB pathogenesis.


Disease Models, Animal , Lung/pathology , Tuberculosis, Pulmonary/pathology , Animals , Bacterial Load , Bronchoscopy , Kidney/microbiology , Kidney/pathology , Liver/microbiology , Liver/pathology , Lung/microbiology , Mycobacterium bovis/growth & development , Mycobacterium bovis/pathogenicity , Rabbits , Spleen/microbiology , Spleen/pathology
13.
Curr Biol ; 20(21): 1881-9, 2010 Nov 09.
Article En | MEDLINE | ID: mdl-20951045

BACKGROUND: During cytokinesis, regulatory signals are presumed to emanate from the mitotic spindle. However, what these signals are and how they lead to the spatiotemporal changes in the cortex structure, mechanics, and regional contractility are not well understood in any system. RESULTS: To investigate pathways that link the microtubule network to the cortical changes that promote cytokinesis, we used chemical genetics in Dictyostelium to identify genetic suppressors of nocodazole, a microtubule depolymerizer. We identified 14-3-3 and found that it is enriched in the cortex, helps maintain steady-state microtubule length, contributes to normal cortical tension, modulates actin wave formation, and controls the symmetry and kinetics of cleavage furrow contractility during cytokinesis. Furthermore, 14-3-3 acts downstream of a Rac small GTPase (RacE), associates with myosin II heavy chain, and is needed to promote myosin II bipolar thick filament remodeling. CONCLUSIONS: 14-3-3 connects microtubules, Rac, and myosin II to control several aspects of cortical dynamics, mechanics, and cytokinesis cell shape change. Furthermore, 14-3-3 interacts directly with myosin II heavy chain to promote bipolar thick filament remodeling and distribution. Overall, 14-3-3 appears to integrate several critical cytoskeletal elements that drive two important processes-cytokinesis cell shape change and cell mechanics.


14-3-3 Proteins/physiology , Cytokinesis/physiology , Dictyostelium/cytology , Microtubules/metabolism , Myosin Type II/metabolism , Nocodazole/pharmacology , rac GTP-Binding Proteins/metabolism , 14-3-3 Proteins/genetics , 14-3-3 Proteins/metabolism , Cytokinesis/genetics , Dictyostelium/genetics , Dictyostelium/ultrastructure , Down-Regulation , Gene Library , Microtubules/drug effects , Microtubules/ultrastructure , Myosin Type II/physiology , Nocodazole/antagonists & inhibitors , rac GTP-Binding Proteins/physiology
14.
Science ; 328(5977): 463-6, 2010 Apr 23.
Article En | MEDLINE | ID: mdl-20413492

Argument and debate are common in science, yet they are virtually absent from science education. Recent research shows, however, that opportunities for students to engage in collaborative discourse and argumentation offer a means of enhancing student conceptual understanding and students' skills and capabilities with scientific reasoning. As one of the hallmarks of the scientist is critical, rational skepticism, the lack of opportunities to develop the ability to reason and argue scientifically would appear to be a significant weakness in contemporary educational practice. In short, knowing what is wrong matters as much as knowing what is right. This paper presents a summary of the main features of this body of research and discusses its implications for the teaching and learning of science.


Communication , Comprehension , Dissent and Disputes , Learning , Science/education , Teaching , Thinking , Humans
19.
Otol Neurotol ; 26(5): 846-52, 2005 Sep.
Article En | MEDLINE | ID: mdl-16151327

OBJECTIVE: To report an original method of ossicular reconstruction with intact stapes and absent malleus. Ossiculoplasty is performed with a total ossicular replacement prosthesis positioned from the stapes footplate to the under-surface of the tympanic membrane, using a Silastic banding technique to stabilize the prosthesis. STUDY DESIGN: A prospective study of ossicular reconstruction using the Silastic banding technique. A consecutive series of cases with intact stapes superstructure and missing malleus handle (Austin-Kartush Group C) is presented. SETTING: One tertiary referral center. PATIENTS: Ninety-nine patients who underwent total ossicular reconstruction with Silastic banding technique were enrolled in the study from January 2000 to December 2002. INTERVENTIONS: Ossiculoplasty with total ossicular replacement prostheses with Silastic Rubber Band for chronic otitis media and non-inflammatory disease. MAIN OUTCOME MEASURES: Preoperative and postoperative audiometric evaluation using conventional audiometry. Air-bone gap, bone-conduction threshold, and air-conduction threshold were assessed. Postoperative audiometry was performed at the 6th, 9th, 12th, 18th, 24th, and 36th months. RESULTS: Overall, a postoperative air-bone gap closed to within 10 dB was achieved in 61.5% of cases. An air-bone gap smaller than 20 dB was obtained in 77% of cases. Postoperative improvement of air-conduction thresholds by at least 20 dB was found in 51% of cases. There was no case of postoperative sensorineural hearing loss. One case of extrusion of the prosthesis was seen (1%). CONCLUSION: Stabilizing the total ossicular replacement prosthesis with the Silastic banding technique when performing ossicular reconstruction is a safe, effective method when the stapes supra-structure is present and the malleus absent.


Ear Diseases/surgery , Ear Ossicles/surgery , Ossicular Replacement/methods , Adolescent , Adult , Aged , Aged, 80 and over , Audiometry, Pure-Tone , Auditory Threshold , Bone Conduction , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications , Prospective Studies , Reoperation , Tomography, X-Ray Computed , Treatment Outcome
20.
Otol Neurotol ; 26(5): 988-98, 2005 Sep.
Article En | MEDLINE | ID: mdl-16151348

OBJECTIVE: To evaluate the speech perception benefits of bilateral implantation for subjects who already have one implant. STUDY DESIGN: Repeated measures. PATIENTS: Thirty adult cochlear implant users who received their second implant from 1 to 7 years with a mean of 3 years after their first device. Ages ranged from 29 to 82 years with a mean of 57 years. SETTING: Tertiary referral centers across the United Kingdom. MAIN OUTCOME MEASURES: Monosyllabic consonant-nucleus-consonant words and City University of New York sentences in quiet with coincident speech and noise and with the noise spatially separated from the speech by +/-90 degrees . RESULTS: At 9 months, results showed the second ear in noise was 13.9 +/- 5.9% worse than the first ear (p < 0.001); a significant binaural advantage of 12.6 +/- 5.4% (p < 0.001) over the first ear alone for speech and noise from the front; a 21 +/- 6% (p < 0.001) binaural advantage over the first ear alone when noise was ipsilateral to the first ear; no binaural advantage when noise was contralateral to the first ear. CONCLUSIONS: There is a significant bilateral advantage of adding a second ear for this group. We were unable to predict when the second ear would be the better performing ear, and by implanting both ears, we guarantee implanting the better ear. Sequential implantation with long delays between ears has resulted in poor second ear performance for some subjects and has limited the degree of bilateral benefit that can be obtained by these users. The dual microphone does not provide equivalent benefit to bilateral implants.


Cochlear Implants , Speech Perception , Adult , Aged , Aged, 80 and over , Cochlear Implantation , Deafness/rehabilitation , Female , Humans , Male , Middle Aged , Speech Discrimination Tests , Treatment Outcome
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