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"Boyd, D."
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Paulo Freire : his faith, spirituality, and theology
Paulo Freire (1921?1997) is well known around the world for his innovative educational philosophy, which has led many to consider him the ?father? of both critical pedagogy and popular education. What is less known about Freire, however, is that his politics and pedagogy were informed by a faith birthed in Roman Catholicism, but which also challenged the church to move beyond individual piety to prophetic action. Freire?s spirituality was rooted in the conviction that God calls all people of goodwill to work toward fulfilling the vision of a new humanity given by God. To that end, this book - one of the first of its kind discussing Freire - examines the spirituality that was foundational to his life and teaching, inviting all who have been influenced by Freire to consider the deeper spiritual dimensions of their pedagogical and political work.
BOOK
A c-di-GMP Effector System Controls Cell Adhesion by Inside-Out Signaling and Surface Protein Cleavage
In Pseudomonas fluorescens Pf0-1 the availability of inorganic phosphate (Pi) is an environmental signal that controls biofilm formation through a cyclic dimeric GMP (c-di-GMP) signaling pathway. In low Pi conditions, a c-di-GMP phosphodiesterase (PDE) RapA is expressed, depleting cellular c-di-GMP and causing the loss of a critical outer-membrane adhesin LapA from the cell surface. This response involves an inner membrane protein LapD, which binds c-di-GMP in the cytoplasm and exerts a periplasmic output promoting LapA maintenance on the cell surface. Here we report how LapD differentially controls maintenance and release of LapA: c-di-GMP binding to LapD promotes interaction with and inhibition of the periplasmic protease LapG, which targets the N-terminus of LapA. We identify conserved amino acids in LapA required for cleavage by LapG. Mutating these residues in chromosomal lapA inhibits LapG activity in vivo, leading to retention of the adhesin on the cell surface. Mutations with defined effects on LapD's ability to control LapA localization in vivo show concomitant effects on c-di-GMP-dependent LapG inhibition in vitro. To establish the physiological importance of the LapD-LapG effector system, we track cell attachment and LapA protein localization during Pi starvation. Under this condition, the LapA adhesin is released from the surface of cells and biofilms detach from the substratum. This response requires c-di-GMP depletion by RapA, signaling through LapD, and proteolytic cleavage of LapA by LapG. These data, in combination with the companion study by Navarro et al. presenting a structural analysis of LapD's signaling mechanism, give a detailed description of a complete c-di-GMP control circuit--from environmental signal to molecular output. They describe a novel paradigm in bacterial signal transduction: regulation of a periplasmic enzyme by an inner membrane signaling protein that binds a cytoplasmic second messenger.
Journal Article
Navigating life with migraine and other headaches
\"Navigating Life with Migraine and Other Headaches focuses on the many myths that exist around headaches and dispels common misperceptions by providing simple explanations on how headaches occur, and, most importantly, how to treat them. The authors give real, practical advice: when and how to manage your headaches, when to seek treatment, and when to be concerned. From vitamins to prescription meds; from when to go to the emergency department to optimizing doctor visits; options for managing headaches are presented in this accessible and easy-to-read resource. The more you know about headache, including the mechanisms that cause pain, the better you and your family can manage this common and chronic condition. Through the use of patient stories, a glossary of terms for easy reference, and key points for quick retention, this book is a high-quality resource for people looking for empowerment and a sense of control\"--Provided by publisher.
Book
Diversity and clonal selection in the human T-cell repertoire
T-cell receptor (TCR) diversity, a prerequisite for immune system recognition of the universe of foreign antigens, is generated in the first two decades of life in the thymus and then persists to an unknown extent through life via homeostatic proliferation of naïve T cells. We have used next-generation sequencing and nonparametric statistical analysis to estimate a lower bound for the total number of different TCR beta (TCRB) sequences in human repertoires. We arrived at surprisingly high minimal estimates of 100 million unique TCRB sequences in naïve CD4 and CD8 T-cell repertoires of young adults. Naïve repertoire richness modestly declined two-to fivefold in healthy elderly. Repertoire richness contraction with age was even less pronounced for memory CD4 and CD8 T cells. In contrast, age had a major impact on the inequality of donai sizes, as estimated by a modified Gini-Simpson index clonality score. In particular, large naïve T-cell clones that were distinct from memory clones were found in the repertoires of elderly individuals, indicating uneven homeostatic proliferation without development of a memory cell phenotype. Our results suggest that a highly diverse repertoire is maintained despite thymic involution; however, peripheral fitness selection of T cells leads to repertoire perturbations that can influence the immune response in the elderly.
Journal Article
Wilkins' clinical practice of the dental hygienist
Walking dental hygiene students step-by-step through everything they need to know.
Book
The biogeography of the Plastisphere: implications for policy
Microplastics (particles less than 5 mm) numerically dominate marine debris and occur from coastal waters to mid-ocean gyres, where surface circulation concentrates them. Given the prevalence of plastic marine debris (PMD) and the rise in plastic production, the impacts of plastic on marine ecosystems will likely increase. Microscopic life (the \"Plastisphere\") thrives on these tiny floating \"islands\" of debris and can be transported long distances. Using next-generation DNA sequencing, we characterized bacterial communities from water and plastic samples from the North Pacific and North Atlantic subtropical gyres to determine whether the composition of different Plastisphere communities reflects their biogeographic origins. We found that these communities differed between ocean basins - and to a lesser extent between polymer types - and displayed latitudinal gradients in species richness. Our research reveals some of the impacts of microplastics on marine biodiversity, demonstrates that the effects and fate of PMD may vary considerably in different parts of the global ocean, and suggests that PMD mitigation will require regional management efforts.
Journal Article
Cerium oxide nanoparticles with antioxidant capabilities and gadolinium integration for MRI contrast enhancement
The chelating gadolinium-complex is routinely used as magnetic resonance imaging (MRI) -contrast enhancer. However, several safety issues have recently been reported by FDA and PRAC. There is an urgent need for the next generation of safer MRI-contrast enhancers, with improved local contrast and targeting capabilities. Cerium oxide nanoparticles (CeNPs) are designed with fractions of up to 50% gadolinium to utilize the superior MRI-contrast properties of gadolinium. CeNPs are well-tolerated
in vivo
and have redox properties making them suitable for biomedical applications, for example scavenging purposes on the tissue- and cellular level and during tumor treatment to reduce
in vivo
inflammatory processes. Our near edge X-ray absorption fine structure (NEXAFS) studies show that implementation of gadolinium changes the initial co-existence of oxidation states Ce
3+
and Ce
4+
of cerium, thereby affecting the scavenging properties of the nanoparticles. Based on a
b initio
electronic structure calculations, we describe the most prominent spectral features for the respective oxidation states. The as-prepared gadolinium-implemented CeNPs are 3–5 nm in size, have r
1
-relaxivities between 7–13 mM
−1
s
−1
and show clear antioxidative properties, all of which means they are promising theranostic agents for use in future biomedical applications.
Journal Article
Spontaneous cortical activity alternates between motifs defined by regional axonal projections
Using voltage sensitive–dye imaging in the cortices of anesthetized and awake mice, the authors show that spontaneous activity patterns contain similar motifs as those evoked by sensory stimulation. These motifs are also seen after optogenetic activation of the cortex, and they correlate with structural connectivity.
Using millisecond-timescale voltage-sensitive dye imaging in lightly anesthetized or awake adult mice, we show that a palette of sensory-evoked and hemisphere-wide activity motifs are represented in spontaneous activity. These motifs can reflect multiple modes of sensory processing, including vision, audition and touch. We found similar cortical networks with direct cortical activation using channelrhodopsin-2. Regional analysis of activity spread indicated modality-specific sources, such as primary sensory areas, a common posterior-medial cortical sink where sensory activity was extinguished within the parietal association area and a secondary anterior medial sink within the cingulate and secondary motor cortices for visual stimuli. Correlation analysis between functional circuits and intracortical axonal projections indicated a common framework corresponding to long-range monosynaptic connections between cortical regions. Maps of intracortical monosynaptic structural connections predicted hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We suggest that an intracortical monosynaptic connectome shapes the ebb and flow of spontaneous cortical activity.
Journal Article
Defining antigen-specific plasmablast and memory B cell subsets in human blood after viral infection or vaccination
Immunologic memory promotes faster and more-efficient responses after re-exposure to pathogens. Ahmed and colleagues characterize a subset of human B cells that arise after vaccination against or exposure to influenza or Ebola virus and contribute to the memory cell pool.
Antigen-specific B cells bifurcate into antibody-secreting cells (ASCs) and memory B cells (MBCs) after infection or vaccination. ASCs (plasmablasts) have been extensively studied in humans, but less is known about B cells that become activated but do not differentiate into plasmablasts. Here we have defined the phenotype and transcriptional program of a subset of antigen-specific B cells, which we have called 'activated B cells' (ABCs), that were distinct from ASCs and were committed to the MBC lineage. We detected ABCs in humans after infection with Ebola virus or influenza virus and also after vaccination. By simultaneously analyzing antigen-specific ASCs and ABCs in human blood after vaccination against influenza virus, we investigated the clonal overlap and extent of somatic hypermutation (SHM) in the ASC (effector) and ABC (memory) lineages. Longitudinal tracking of vaccination-induced hemagglutinin (HA)-specific clones revealed no overall increase in SHM over time, which suggested that repeated annual immunization might have limitations in enhancing the quality of influenza-virus-specific antibody.
Journal Article
Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire
Variation in the antibody response has been linked to differential outcomes in disease, and suboptimal vaccine and therapeutic responsiveness, the determinants of which have not been fully elucidated. Countering models that presume antibodies are generated largely by stochastic processes, we demonstrate that polymorphisms within the immunoglobulin heavy chain locus (IGH) impact the naive and antigen-experienced antibody repertoire, indicating that genetics predisposes individuals to mount qualitatively and quantitatively different antibody responses. We pair recently developed long-read genomic sequencing methods with antibody repertoire profiling to comprehensively resolve IGH genetic variation, including novel structural variants, single nucleotide variants, and genes and alleles. We show that IGH germline variants determine the presence and frequency of antibody genes in the expressed repertoire, including those enriched in functional elements linked to V(D)J recombination, and overlapping disease-associated variants. These results illuminate the power of leveraging IGH genetics to better understand the regulation, function, and dynamics of the antibody response in disease.
Haplotype diversity in the human immunoglobulin heavy chain (IGH) locus is poorly characterized. Here, the authors use long-read sequencing to discover extensive IGH diversity and link germline variants to variation in the antibody repertoire.
Journal Article