NMR Studies on Structure and Dynamics of the Monomeric Derivative of BS-RNase: New Insights for 3D Domain Swapping

Three-dimensional domain swapping is a common phenomenon in pancreatic-like ribonucleases. In the aggregated state, these proteins acquire new biological functions, including selective cytotoxicity against tumour cells. RNase A is able to dislocate both N- and C-termini, but usually this process requires denaturing conditions. In contrast, bovine seminal ribonuclease (BS-RNase), which is a homo-dimeric protein sharing 80% of sequence identity with RNase A, occurs natively as a mixture of swapped and unswapped isoforms. The presence of two disulfides bridging the subunits, indeed, ensures a dimeric structure also to the unswapped molecule. In vitro, the two BS-RNase isoforms interconvert under physiological conditions. Since the tendency to swap is often related to the instability of the monomeric proteins, in these paper we have analysed in detail the stability in solution of the monomeric derivative of BS-RNase (mBS) by a combination of NMR studies and Molecular Dynamics Simulations. The refinement of NMR structure and relaxation data indicate a close similarity with RNase A, without any evidence of aggregation or partial opening. The high compactness of mBS structure is confirmed also by H/D exchange, urea denaturation, and TEMPOL mapping of the protein surface. The present extensive structural and dynamic investigation of (monomeric) mBS did not show any experimental evidence that could explain the known differences in swapping between BS-RNase and RNase A. Hence, we conclude that the swapping in BS-RNase must be influenced by the distinct features of the dimers, suggesting a prominent role for the interchain disulfide bridges

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

The Fundamental Relevance of Morphology and Morphogenesis to Plant Research

Plant morphology, including morphogenesis, remains relevant to practically all disciplines of plant biology such as molecular genetics, physiology, ecology, evolutionary biology and systematics. This relevance derives from the fact that other disciplines refer to or imply morphological concepts, conceptual frameworks of morphology, and morphological theories. Most commonly, morphology is equated with classical morphology and its conceptual framework. According to this, flowering plants and certain other taxa are reduced to the mutually exclusive categories of root, stem (caulome) and leaf (phyllome). This ignores the fact that plant morphology has undergone fundamental conceptual, theoretical and philosophical innovation in recent times. These changes, when recognized, can fundamentally affect research in various disciplines of plant biology. They may even change the questions that are asked and thus may affect the direction of future research. If, for example, plant diversity and evolution are seen as a dynamic continuum, then compound leaves can be seen as intermediate between simple leaves and whole shoots. Recent results in molecular genetics support this view. Phylogenetically, this could mean that compound leaves are the result of developmental hybridization, i.e. partial homeosis. Many other examples are given to illustrate the relevance and potential impact of basic conceptual and theoretical innovations in plant morphology.Copyright 1997 Annals of Botany Compan

Fundamentals of Plant Morphology and Plant Evo-Devo (Evolutionary Developmental Morphology)

Morphological concepts are used in plant evo-devo (evolutionary developmental biology) and other disciplines of plant biology, and therefore plant morphology is relevant to all of these disciplines. Many plant biologists still rely on classical morphology, according to which there are only three mutually exclusive organ categories in vascular plants such as flowering plants: root, stem (caulome), and leaf (phyllome). Continuum morphology recognizes a continuum between these organ categories. Instead of Aristotelian identity and either/or logic, it is based on fuzzy logic, according to which membership in a category is a matter of degree. Hence, an organ in flowering plants may be a root, stem, or leaf to some degree. Homology then also becomes a matter of degree. Process morphology supersedes structure/process dualism. Hence, structures do not have processes, they are processes, which means they are process combinations. These process combinations may change during ontogeny and phylogeny. Although classical morphology on the one hand and continuum and process morphology on the other use different kinds of logic, they can be considered complementary and thus together they present a more inclusive picture of the diversity of plant form than any one of the three alone. However, continuum and process morphology are more comprehensive than classical morphology. Insights gained from continuum and process morphology can inspire research in plant morphology and plant evo-devo, especially MorphoEvoDevo

Morpho Evo-Devo of the Gynoecium: Heterotopy, Redefinition of the Carpel, and a Topographic Approach

Since the 19th century, we have had countless debates, sometimes acrimonious, about the nature of the gynoecium. A pivotal question has been whether all angiosperms possess carpels or if some or all angiosperms are acarpellate. We can resolve these debates if we do not define the carpel as a closed megasporophyll but simply as an appendage that encloses the placenta or a single ovule. This redefinition may, however, lead to confusion because often it may not be clear whether the traditional (classical) definition of the carpel or the redefinition is implied. Therefore, a topographic approach is proposed that is compatible with the redefinition. According to this approach, gynoecia comprise one or more gynoecial appendages and placentas or single ovules that may be formed in different positions. Heterotopy refers to these different positions. In the context of evo-devo, which explores evolutionary changes in development, morpho evo-devo delves into spatial shifts of the placentas and ovules leading to heterotopy. Furthermore, it considers shifts in timing (heterochrony) and other processes leading to heteromorphy. Recognizing spatial shifting of the placentas or a single ovule and other evolutionary processes opens up new vistas in the search for the ancestor(s) of angiosperms and their gynoecia

Prevalence Estimates for Pharmacological Neuroenhancement in Austrian University Students: Its Relation to Health-Related Risk Attitude and the Framing Effect of Caffeine Tablets

Background: Pharmacological neuroenhancement (PN) is defined as the use of illicit or prescription drugs by healthy individuals for cognitive-enhancing purposes. The present study aimed (i) to investigate whether including caffeine tablets in the definition of PN within a questionnaire increases the PN prevalence estimate (framing effect), (ii) to investigate whether the health-related risk attitude is increased in students who use PN.Materials and methods: Two versions of a paper-and-pencil questionnaire (first version included caffeine tablets in the definition of PN, the second excluded caffeine tablets) were distributed among university students at the University of Graz, Austria. The unrelated question model (UQM) was used to estimate the 12-month PN prevalence and the German version of the 30-item Domain-Specific Risk-Taking (DOSPERT) scale to assess the health-related risk attitude. Moreover, large-sample z-tests (α = 0.05) were performed for comparing the PN prevalence estimates of two groups.Results: Two thousand four hundred and eighty-nine questionnaires were distributed and 2,284 (91.8%) questionnaires were included in analysis. The overall PN prevalence estimate for all students was 11.9%. One-tailed large-sample z-tests revealed that the PN estimate for students with higher health-related risk attitude was significantly higher compared to students with lower health-related risk attitude (15.6 vs. 8.5%; z = 2.65, p = 0.004). Furthermore, when caffeine tablets were included into the example of PN, the prevalence estimate of PN was significantly higher compared to the version without caffeine tablets (14.9 vs. 9.0%; z = 2.20, p = 0.014).Discussion: This study revealed that the PN prevalence estimate increases when caffeine tablets are included in the definition of PN. Therefore, future studies investigating the prevalence of, and predictors for, PN should be performed and interpreted with respect to potential framing effects. This study further revealed that the PN prevalence estimate is increased in students with a higher health-related risk attitude compared to students with a lower one. Therefore, future education and prevention programs addressing PN in the collective of students should not only inform about potential side effects of its use but also address the limited effects on cognition and potential alternatives of PN

Legislative Documents

Also, variously referred to as: House bills; House documents; House legislative documents; legislative documents; General Court documents

Data_Sheet_1_Prevalence Estimates for Pharmacological Neuroenhancement in Austrian University Students: Its Relation to Health-Related Risk Attitude and the Framing Effect of Caffeine Tablets.PDF

<p>Background: Pharmacological neuroenhancement (PN) is defined as the use of illicit or prescription drugs by healthy individuals for cognitive-enhancing purposes. The present study aimed (i) to investigate whether including caffeine tablets in the definition of PN within a questionnaire increases the PN prevalence estimate (framing effect), (ii) to investigate whether the health-related risk attitude is increased in students who use PN.</p><p>Materials and methods: Two versions of a paper-and-pencil questionnaire (first version included caffeine tablets in the definition of PN, the second excluded caffeine tablets) were distributed among university students at the University of Graz, Austria. The unrelated question model (UQM) was used to estimate the 12-month PN prevalence and the German version of the 30-item Domain-Specific Risk-Taking (DOSPERT) scale to assess the health-related risk attitude. Moreover, large-sample z-tests (α = 0.05) were performed for comparing the PN prevalence estimates of two groups.</p><p>Results: Two thousand four hundred and eighty-nine questionnaires were distributed and 2,284 (91.8%) questionnaires were included in analysis. The overall PN prevalence estimate for all students was 11.9%. One-tailed large-sample z-tests revealed that the PN estimate for students with higher health-related risk attitude was significantly higher compared to students with lower health-related risk attitude (15.6 vs. 8.5%; z = 2.65, p = 0.004). Furthermore, when caffeine tablets were included into the example of PN, the prevalence estimate of PN was significantly higher compared to the version without caffeine tablets (14.9 vs. 9.0%; z = 2.20, p = 0.014).</p><p>Discussion: This study revealed that the PN prevalence estimate increases when caffeine tablets are included in the definition of PN. Therefore, future studies investigating the prevalence of, and predictors for, PN should be performed and interpreted with respect to potential framing effects. This study further revealed that the PN prevalence estimate is increased in students with a higher health-related risk attitude compared to students with a lower one. Therefore, future education and prevention programs addressing PN in the collective of students should not only inform about potential side effects of its use but also address the limited effects on cognition and potential alternatives of PN.</p