1,441 research outputs found

    Identification of a WNT5A-Responsive Degradation Domain in the Kinesin Superfamily Protein KIF26B.

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    Noncanonical WNT pathways function independently of the β-catenin transcriptional co-activator to regulate diverse morphogenetic and pathogenic processes. Recent studies showed that noncanonical WNTs, such as WNT5A, can signal the degradation of several downstream effectors, thereby modulating these effectors' cellular activities. The protein domain(s) that mediates the WNT5A-dependent degradation response, however, has not been identified. By coupling protein mutagenesis experiments with a flow cytometry-based degradation reporter assay, we have defined a protein domain in the kinesin superfamily protein KIF26B that is essential for WNT5A-dependent degradation. We found that a human disease-causing KIF26B mutation located at a conserved amino acid within this domain compromises the ability of WNT5A to induce KIF26B degradation. Using pharmacological perturbation, we further uncovered a role of glycogen synthase kinase 3 (GSK3) in WNT5A regulation of KIF26B degradation. Lastly, based on the identification of the WNT5A-responsive domain, we developed a new reporter system that allows for efficient profiling of WNT5A-KIF26B signaling activity in both somatic and stem cells. In conclusion, our study identifies a new protein domain that mediates WNT5A-dependent degradation of KIF26B and provides a new tool for functional characterization of noncanonical WNT5A signaling in cells

    Millimeter Wave Localization: Slow Light and Enhanced Absorption

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    We exploit millimeter wave technology to measure the reflection and transmission response of random dielectric media. Our samples are easily constructed from random stacks of identical, sub-wavelength quartz and Teflon wafers. The measurement allows us to observe the characteristic transmission resonances associated with localization. We show that these resonances give rise to enhanced attenuation even though the attenuation of homogeneous quartz and Teflon is quite low. We provide experimental evidence of disorder-induced slow light and superluminal group velocities, which, in contrast to photonic crystals, are not associated with any periodicity in the system. Furthermore, we observe localization even though the sample is only about four times the localization length, interpreting our data in terms of an effective cavity model. An algorithm for the retrieval of the internal parameters of random samples (localization length and average absorption rate) from the external measurements of the reflection and transmission coefficients is presented and applied to a particular random sample. The retrieved value of the absorption is in agreement with the directly measured value within the accuracy of the experiment.Comment: revised and expande

    A tale of two sites: how inflammation can reshape the microbiomes of the gut and lungs

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141495/1/jlb0943.pd

    Vancomycin-induced deletion of the methicillin resistance gene mecA in Staphylococcus aureus

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    Objective: To elucidate factors that contribute to the development of vancomycin resistance in methicillin-resistant Staphylococcus aureus (MRSA). Methods: Forty-nine MRSA isolates were subjected to passage selection with vancomycin to isolate mutants with reduced susceptibility to vancomycin. One mutant was chosen for detailed molecular and biochemical characterization. Results: Five vancomycin-resistant mutants (vancomycin MICs, 6-12 mg/L) were obtained in vitro from five MRSA parent isolates. Upon acquisition of vancomycin resistance, all mutants showed a concomitant decrease in oxacillin resistance. In one particular MRSA strain, selection for vancomycin resistance repeatedly produced deletions and rearrangements, including loss of the mecA gene. Pleiotropic phenotypical changes, such as yellow pigment formation, loss of haemolysis, thickened cell wall, increased resistance to lysostaphin and reduced cell wall turnover were observed in this mutant. Conclusion: Acquisition of vancomycin resistance in one MRSA strain triggered mecA deletion suggesting that this deletion, coupled to other rearrangements and/or mutations, may be responsible for the increased vancomycin resistance phenotyp

    Energizers Classroom-based Physical Activities 3-5 : The way teachers integrate physical activity with academic concepts

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    Energizers are classroom-based physical activities that were designed to help teachers integrate physical activity with academic concepts. The energizers were developed by a team from the Activity Promotion Laboratory at East Carolina University. Teachers can download these activities free of charge and are encouraged to incorporate these activities into their classroom. Our research, published in the journal Medicine and Science in Sports and Exercise (2006, volume 38, number 12), demonstrated that: (a) Energizers are easy to implement; (b) both teachers and students enjoy the Energizers activities; (c) use of Energizers activities improves on-task behavior of students; and (d) use of Energizers increases the amount of physical activity accumulated over the course of the school day.Activity Promotion Laboratory: Projects Fulfilling a Nee

    Music Middle-School Energizers Classroom-based Physical Activities The way teachers integrate physical activity with academic concepts

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    Middle School Energizers are classroom-based physical activities that integrate physical activity with academic concepts. The Middle School Energizers were developed by a team from the Activity Promotion Laboratory at East Carolina University. We hope these 10-minute activities make it easier for teachers to implement physical activity into the classroom to improve classroom instruction and increase physical activity levels over the school day. Teachers can download these activities free of charge and are encouraged to incorporate these activities into their classroomActivity Promotion Laboratory: Projects Fulfilling a Nee

    Healthful Living Middle-School Energizers Classroom-based Physical Activities The way teachers integrate physical activity with academic concepts

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    Middle School Energizers Middle School Energizers are classroom-based physical activities that integrate physical activity with academic concepts. The Middle School Energizers were developed by a team from the Activity Promotion Laboratory at East Carolina University. We hope these 10-minute activities make it easier for teachers to implement physical activity into the classroom to improve classroom instruction and increase physical activity levels over the school day. Teachers can download these activities free of charge and are encouraged to incorporate these activities into their classroom.Activity Promotion Laboratory: Projects Fulfilling a Nee

    Social Studies Middle-School Energizers Classroom-based Physical Activities The way teachers integrate physical activity with academic concepts

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    Activity Promotion Laboratory: Projects Fulfilling a NeedMiddle School Energizers Middle School Energizers are classroom-based physical activities that integrate physical activity with academic concepts. The Middle School Energizers were developed by a team from the Activity Promotion Laboratory at East Carolina University. We hope these 10-minute activities make it easier for teachers to implement physical activity into the classroom to improve classroom instruction and increase physical activity levels over the school day. Teachers can download these activities free of charge and are encouraged to incorporate these activities into their classroom.Activity Promotion Laboratory: Projects Fulfilling a Nee

    Scattering from a large cylinder with an eccentrically embedded core: An orders-of-scattering approximation,”

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    a b s t r a c t We develop an orders-of-scattering approximation, termed the "screened cylindrical void/ core" (SCV) approximation, for a composite cylinder. The composite cylinder consists of a large host cylinder that contains a small, eccentrically embedded, core cylinder. The SCV approximation is developed via separation of variables in conjunction with addition theorems for cylindrical functions. We show that the SCV approximation is in good agreement with the numerically exact solution. A simple physical interpretation of the SCV approximation is also presented
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