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Secondary Structures of rRNAs from All Three Domains of Life
Accurate secondary structures are important for understanding ribosomes, which are extremely large and highly complex. Using 3D structures of ribosomes as input, we have revised and corrected traditional secondary (2°) structures of rRNAs. We identify helices by specific geometric and molecular interaction criteria, not by co-variation. The structural approach allows us to incorporate non-canonical base pairs on parity with Watson-Crick base pairs. The resulting rRNA 2° structures are up-to-date and consistent with three-dimensional structures, and are information-rich. These 2° structures are relatively simple to understand and are amenable to reproduction and modification by end-users. The 2° structures made available here broadly sample the phylogenetic tree and are mapped with a variety of data related to molecular interactions and geometry, phylogeny and evolution. We have generated 2° structures for both large subunit (LSU) 23S/28S and small subunit (SSU) 16S/18S rRNAs of Escherichia coli, Thermus thermophilus, Haloarcula marismortui (LSU rRNA only), Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens. We provide high-resolution editable versions of the 2° structures in several file formats. For the SSU rRNA, the 2° structures use an intuitive representation of the central pseudoknot where base triples are presented as pairs of base pairs. Both LSU and SSU secondary maps are available (http://apollo.chemistry.gatech.edu/RibosomeGallery). Mapping of data onto 2° structures was performed on the RiboVision server (http://apollo.chemistry.gatech.edu/RiboVision).
Journal Article
Contemporary developments in games teaching
The teaching of games is a central component of any physical education or youth sport programme. This book brings together leading international researchers and practitioners in physical education and sports coaching to examine new approaches in games teaching and team sport coaching that are player/student-centred and inquiry-based.
Book
History of the ribosome and the origin of translation
We present a molecular-level model for the origin and evolution of the translation system, using a 3D comparative method. In this model, the ribosome evolved by accretion, recursively adding expansion segments, iteratively growing, subsuming, and freezing the rRNA. Functions of expansion segments in the ancestral ribosome are assigned by correspondence with their functions in the extant ribosome. The model explains the evolution of the large ribosomal subunit, the small ribosomal subunit, tRNA, and mRNA. Prokaryotic ribosomes evolved in six phases, sequentially acquiring capabilities for RNA folding, catalysis, subunit association, correlated evolution, decoding, energy-driven translocation, and surface proteinization. Two additional phases exclusive to eukaryotes led to tentacle-like rRNA expansions. In this model, ribosomal proteinization was a driving force for the broad adoption of proteins in other biological processes. The exit tunnel was clearly a central theme of all phases of ribosomal evolution and was continuously extended and rigidified. In the primitive noncoding ribosome, proto-mRNA and the small ribosomal subunit acted as cofactors, positioning the activated ends of tRNAs within the peptidyl transferase center. This association linked the evolution of the large and small ribosomal subunits, proto-mRNA, and tRNA.
Journal Article
The entropic force generated by intrinsically disordered segments tunes protein function
Protein structures are dynamic and can explore a large conformational landscape
1
,
2
. Only some of these structural substates are important for protein function (such as ligand binding, catalysis and regulation)
3
–
5
. How evolution shapes the structural ensemble to optimize a specific function is poorly understood
3
,
4
. One of the constraints on the evolution of proteins is the stability of the folded ‘native’ state. Despite this, 44% of the human proteome contains intrinsically disordered peptide segments greater than 30 residues in length
6
, the majority of which have no known function
7
–
9
. Here we show that the entropic force produced by an intrinsically disordered carboxy terminus (ID-tail) shifts the conformational ensemble of human UDP-α-
d
-glucose-6-dehydrogenase (UGDH) towards a substate with a high affinity for an allosteric inhibitor. The function of the ID-tail does not depend on its sequence or chemical composition. Instead, the affinity enhancement can be accurately predicted based on the length of the intrinsically disordered segment, and is consistent with the entropic force generated by an unstructured peptide attached to the protein surface
10
–
13
. Our data show that the unfolded state of the ID-tail rectifies the dynamics and structure of UGDH to favour inhibitor binding. Because this entropic rectifier does not have any sequence or structural constraints, it is an easily acquired adaptation. This model implies that evolution selects for disordered segments to tune the energy landscape of proteins, which may explain the persistence of intrinsic disorder in the proteome.
The carboxy terminus of human UDP-α-
d
-glucose-6-dehydrogenase is structurally disordered, but has sequence-independent effects on the conformation of the enzyme and binding of an allosteric inhibitor, suggesting a reason for the persistence of intrinsically disordered peptide segments in the proteome.
Journal Article
Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity
While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4(+) T cells. Also among women with genital tract Chlamydia infection, peripheral CD3(+) CD4(+) and CD3(+) CD4(-) cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures.
Journal Article
Impact of a hybrid TGfU-Sport Education unit on student motivation in physical education
The Teaching Games for Understanding (TGfU) and Sport Education (SE) pedagogical models share several objectives and pedagogical processes. Despite this seemingly uncanny relationship, few studies have examined the efficacy of a hybrid TGfU/SE pedagogical model, particularly how a teacher's utilization of such a model impacts on student motivation. The purpose of the current study was to investigate the effect a hybrid TGfU/SE unit, in comparison to direct instruction, on students' perceptions of various aspects of their motivation to engage in physical education (autonomous motivation, basic psychological needs, enjoyment and intention to be physically active). A crossover design was utilized, using the technique of counterbalancing. One group experienced a hybrid SE/TGfU unit first, followed by a unit of direct instruction. A second group experienced the units in the opposite order. Participants were 55 students. The intervention was conducted over a total of 16 lessons. The hybrid unit was designed according to the characteristics of SE by using seasons, roles, persistent teams, etc. Learning tasks set by the teacher during individual lessons, however, were designed according to the pedagogical principles of TGfU. Student motivation data was generated using validated questionnaires. Results showed that regardless of the order of intervention, the two groups showed significant improvements in autonomy, competence and enjoyment when they were taught using the hybrid model. Instead, in the variables autonomous motivation, relatedness and intention to be physically active there were no significant improvements in one group. These results demonstrate that it is possible to design varied learning situations in which affiliation, leadership and trust are fostered, while tasks are adapted to the characteristics of the students. All this can cause greater autonomous motivation, and consequently, perceived competence in the student, a positive image of the sport to practice, and therefore greater enjoyment and to be physically active.
Journal Article
The Transcriptomic Response of Rat Hepatic Stellate Cells to Endotoxin: Implications for Hepatic Inflammation and Immune Regulation
With their location in the perisinusoidal space of Disse, hepatic stellate cells (HSCs) communicate with all of the liver cell types both by physical association (cell body as well as cytosolic processes penetrating into sinusoids through the endothelial fenestrations) and by producing several cytokines and chemokines. Bacterial lipopolysaccharide (LPS), circulating levels of which are elevated in liver diseases and transplantation, stimulates HSCs to produce increased amounts of cytokines and chemokines. Although recent research provides strong evidence for the role of HSCs in hepatic inflammation and immune regulation, the number of HSC-elaborated inflammatory and immune regulatory molecules may be much greater then known at the present time. Here we report time-dependent changes in the gene expression profile of inflammatory and immune-regulatory molecules in LPS-stimulated rat HSCs, and their validation by biochemical analyses. LPS strongly up-regulated LPS-response elements (TLR2 and TLR7) but did not affect TLR4 and down-regulated TLR9. LPS also up-regulated genes in the MAPK, NFκB, STAT, SOCS, IRAK and interferon signaling pathways, numerous CC and CXC chemokines and IL17F. Interestingly, LPS modulated genes related to TGFβ and HSC activation in a manner that would limit their activation and fibrogenic activity. The data indicate that LPS-stimulated HSCs become a major cell type in regulating hepatic inflammatory and immunological responses by altering expression of numerous relevant genes, and thus play a prominent role in hepatic pathophysiology including liver diseases and transplantation.
Journal Article
Evolution of the ribosome at atomic resolution
The origins and evolution of the ribosome, 3–4 billion years ago, remain imprinted in the biochemistry of extant life and in the structure of the ribosome. Processes of ribosomal RNA (rRNA) expansion can be “observed” by comparing 3D rRNA structures of bacteria (small), yeast (medium), and metazoans (large). rRNA size correlates well with species complexity. Differences in ribosomes across species reveal that rRNA expansion segments have been added to rRNAs without perturbing the preexisting core. Here we show that rRNA growth occurs by a limited number of processes that include inserting a branch helix onto a preexisting trunk helix and elongation of a helix. rRNA expansions can leave distinctive atomic resolution fingerprints, which we call “insertion fingerprints.” Observation of insertion fingerprints in the ribosomal common core allows identification of probable ancestral expansion segments. Conceptually reversing these expansions allows extrapolation backward in time to generate models of primordial ribosomes. The approach presented here provides insight to the structure of pre-last universal common ancestor rRNAs and the subsequent expansions that shaped the peptidyl transferase center and the conserved core. We infer distinct phases of ribosomal evolution through which ribosomal particles evolve, acquiring coding and translocation, and extending and elaborating the exit tunnel.
Journal Article
Making Learning Happen in Teaching Games for Understanding with Cognitive Load Theory
Game-Based Approaches (GBAs) to teaching and learning in physical education and sport pedagogy, such as Teaching Games for Understanding (TGfU), were initially developed in response to secondary school physical education (PE) students’ difficulties in applying this technique within context. The early noughties experienced a significant body of work highlighting the benefits of adopting GBAs such as TGfU across physical education and sport pedagogy contexts. A theme residing in much of this work was understanding TGfU through the lens of social constructivism to the point whereby it seemed this was the only lens through which to consider how learning might happen through TGfU and/or related approaches. However, the exclusive alignment between TGfU and social constructivism is not heavily research-informed and/or evidence-supported, and it seems timely to question if other learning theories from cognitive science might help researchers and practitioners understand the benefits of applying a TGfU approach in teaching and coaching. We specifically approach this topic by appreciating Cognitive Load Theory (CLT) and how pedagogical concepts associated with CLT might help develop a new understanding of how TGfU could support learning.
Journal Article