Clinical counterpoint: vitamin D: new actions, new analogs, new therapeutic potential
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In the first report in this series we described the relationships and evolution of 152 individual proteins of the EF-hand subfamilies. Here we add 66 additional proteins and define eight (CDC, TPNV, CLNB, LPS, DGK, 1F8, VIS, TCBP) new subfamilies and seven (CAL, SQUD, CDPK, EFH5, TPP, LAV, CRGP) new unique proteins, which we assume represent new subfamilies. The main focus of this study is the classification of individual EF-hand domains. Five subfamilies--calmodulin, troponin C, essential light chain, regulatory light chain, CDC31/caltractin--and three uniques--call, squidulin, and calcium-dependent protein kinase--are congruent in that all evolved from a common four-domain precursor. In contrast calpain and sarcoplasmic calcium-binding protein (SARC) each evolved from its own one-domain precursor. The remaining 19 subfamilies and uniques appear to have evolved by translocation and splicing of genes encoding the EF-hand domains that were precursors to the congruent eight and to calpain and to SARC. The rates of evolution of the EF-hand domains are slower following formation of the subfamilies and establishment of their functions. Subfamilies are not readily classified by patterns of calcium coordination, interdomain linker stability, and glycine and proline distribution. There are many homoplasies indicating that similar variants of the EF-hand evolved by independent pathways.
This project focuses on finding and utilizing electrical properties (precursors) of power electronic devices and modules whose changes have strong correlations with different modes and levels of degradations in order to realize online and lightweight state of health evaluation and fault diagnosis. Results from this project will contribute to higher safety, reliability, and power density of power electronic components. The approaches mainly include reviewing academic literature and industry practices for state of the art precursor identification and extraction, accelerated life cycles (ALC) of various power modules to create different degradations in-house, and developing techniques for gate-driver-integratable precursor detection circuit. In FY24, the results includes two sets of definitively detected aging precursors (on-state resistance and gate threshold voltage) for two sets of power modules respectively, controlled accelerated lifetime cycling of multiple silicon carbide (SiC) metal-oxide-semiconductor field-effect transistor (MOSFET) modules, and the development and validation of a gate voltage detection system.
This chapter focuses on multielectron reactions in organized assemblies of molecules at the liquid/liquid interface. We describe the thermodynamic and kinetic parameters of such reactions, including the structure of the reaction centers, charge movement along the electron transfer pathways, and the role of electric double layers in artificial photosynthesis. Some examples of artificial photosynthesis at the oil/water interface are considered, including water photooxidation to the molecular oxygen, oxygen photoreduction, photosynthesis of amphiphilic compounds and proton evolution by photochemical processes.
The enzymes involved in the reduction of nitrogenous oxides are thought to be intermediates in denitrification processes. This review examines the roles of nitrate reductase, nitrite reductases, nitric oxide reductase, mechanisms of N-N bond formation, and nitrous oxide reductases.
The evolutionary and developmental changes in the eye muscle innervation, the inner ear, and the vestibulo-ocular reflex are examined. Three eye muscle patterns, based on the innervation by distinct ocular motoneurons populations, can be identified: a lamprey, an elasmobranch, and a bony fish/tetrapod pattern. Four distinct patterns of variation in the vestibular system are described: a hagfish pattern, a lamprey pattern, an elasmobranch pattern, and a bony fish/tetrapod pattern. Developmental data suggest an influence of the hindbrain on ear pattern formation, thus potentially allowing a concomitant change of eye muscle innervation and ear variation. The connections between the ear and the vestibular nuclei and between the vestibular nuclei and ocular motoneurons are reviewed, and the role of neurotrophins for pattern specification is discussed. Three patterns are recognized in central projections: a hagfish pattern, a lamprey pattern, and a pattern for jawed vertebrates. Second-order connections show both similarities and differences between distantly related species such as lampreys and mammals. For example, elasmobranchs lack an internuclear system, which is at best poorly developed in lampreys. It is suggested that the vestibulo-ocular system shows only a limited degree of variation because of the pronounced functional constraints imposed on it.
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The field of study that deals with the origins of life does not have a consensus for a theory of life's origin. An analysis of the range of theories offered shows that they share some common features that may be reliable predictors when considering the possible origins of life on another planet. The fundamental datum dealing with the origins of life is that life appeared early in the history of the Earth, probably before 3.5 Ga and possibly before 3.8 Ga. What might be called the standard theory (the Oparin-Haldane theory) posits the production of organic molecules on the early Earth followed by chemical reactions that produced increased organic complexity leading eventually to organic life capable of reproduction, mutation, and selection using organic material as nutrients. A distinct class of other theories (panspermia theories) suggests that life was carried to Earth from elsewhere--these theories receive some support from recent work on planetary impact processes. Other alternatives to the standard model suggest that life arose as an inorganic (clay) form and/or that the initial energy source was not organic material but chemical energy or sunlight. We find that the entire range of current theories suggests that liquid water is the quintessential environmental criterion for both the origin and sustenance of life. It is therefore of interest that during the time that life appeared on Earth we have evidence for liquid water present on the surface of Mars.
The review is presented of experimental and computational data on the influence of genotoxic modification of bases (deamination, alkylation, oxidation) on the structure and biological functioning of nucleic acids. Pathways are discussed for the influence of modification on coding properties of bases, on possible errors of nucleic acid biosynthesis, and on configurations of nucleotide mispairs. The atomic structure of nucleic acid fragments with modified bases and the role of base damages in mutagenesis and carcinogenesis are considered.
Gravitropism is directed growth of a plant or plant organ in response to gravity and can be divided into the following temporal sequence: perception, transduction, and response. This article is a review of the research on the early events of gravitropism (i.e., phenomena associated with the perception and transduction phases). The two major hypotheses for graviperception are the protoplast-pressure and starch-statolith models. While most researchers support the concept of statoliths, there are suggestions that plants have multiple mechanisms of perception. Evidence supports the hypothesis that the actin cytoskeleton is involved in graviperception/transduction, but the details of these mechanisms remain elusive. A number of recent developments, such as increased use of the molecular genetic approach, magnetophoresis, and laser ablation, have facilitated research in graviperception and have allowed for refinement of the current models. In addition, the entire continuum of acceleration forces from hypo- to hyper-gravity have been useful in studying perception mechanisms. Future interdisciplinary molecular approaches and the availability of sophisticated laboratories on the International Space Station should help to develop new insights into mechanisms of gravitropism in plants.
For the last 3 decades evidence has been accumulating that some types of mammalian cells respond to their mechanically active environment by altering their morphology, growth rate, and metabolism. The study of such responses is very important in understanding, physiological and pathological conditions ranging from bone formation to atherosclerosis. Obtaining this knowledge has been the goal for an active research area in bioengineering termed cell mechanotransduction. The advancement of optical methodologies used in cell biology research has given the tools to elucidate cellular mechanisms that would otherwise be impossible to visualize. Combined with molecular biology techniques, they give engineers invaluable tools in understanding the chemical pathways involved in mechanotransduction. Herein we briefly review the current knowledge on mechanical signal transduction in mammalian cells, focusing on the application of novel optical techniques in the ongoing research.
Patients with balance disorders want answers to the following basic questions: (1) What is causing my problem? and (2) What can be done about my problem? Information to fully answer these questions must include status of both sensory and motor components of the balance control systems. Computerized dynamic posturography (CDP) provides quantitative assessment of both sensory and motor components of postural control along with how the sensory inputs to the brain interact. This paper reviews the scientific basis and clinical applications of CDP. Specifically, studies describing the integration of vestibular inputs with other sensory systems for postural control are briefly summarized. Clinical applications, including assessment, rehabilitation, and management are presented. Effects of aging on postural control along with prevention and management strategies are discussed.
The spatial and temporal regulation of calcium concentration in plant cells depends on the coordinate activities of channels and active transporters located on different organelles and membranes. Several Ca2+ pumps have been identified and characterized by functional expression of plant genes in a yeast mutant (K616). This expression system has opened the way to a genetic and biochemical characterization of the regulatory and catalytic features of diverse Ca2+ pumps. Plant Ca(2+)-ATPases fall into two major types: AtECA1 represents one of four or more members of the type IIA (ER-type) Ca(2+)-ATPases in Arabidopsis, and AtACA2 is one of seven or more members of the type IIB (PM-type) Ca(2+)-ATPases that are regulated by a novel amino terminal domain. Type IIB pumps are widely distributed on membranes, including the PM (plasma membrane), vacuole, and ER (endoplasmic reticulum). The regulatory domain serves multiple functions, including autoinhibition, calmodulin binding, and sites for modification by phosphorylation. This domain, however, is considerably diverse among several type IIB ATPases, suggesting that the pumps are differentially regulated. Understanding of Ca2+ transporters at the molecular level is providing insights into their roles in signaling networks and in regulating fundamental processes of cell biology.
Recent advances in room-temperature, near-IR and visible diode laser sources for tele-communication, high-speed computer networks, and optical data storage applications are enabling a new generation of gas-dynamic and combustion-flow sensors based on laser absorption spectroscopy. In addition to conventional species concentration and density measurements, spectroscopic techniques for temperature, velocity, pressure and mass flux have been demonstrated in laboratory, industrial and technical flows. Combined with fibreoptic distribution networks and ultrasensitive detection strategies, compact and portable sensors are now appearing for a variety of applications. In many cases, the superior spectroscopic quality of the new laser sources compared with earlier cryogenic, mid-IR devices is allowing increased sensitivity of trace species measurements, high-precision spectroscopy of major gas constituents, and stable, autonomous measurement systems. The purpose of this article is to review recent progress in this field and suggest likely directions for future research and development. The various laser-source technologies are briefly reviewed as they relate to sensor applications. Basic theory for laser absorption measurements of gas-dynamic properties is reviewed and special detection strategies for the weak near-IR and visible absorption spectra are described. Typical sensor configurations are described and compared for various application scenarios, ranging from laboratory research to automated field and airborne packages. Recent applications of gas-dynamic sensors for air flows and fluxes of trace atmospheric species are presented. Applications of gas-dynamic and combustion sensors to research and development of high-speed flows aeropropulsion engines, and combustion emissions monitoring are presented in detail, along with emerging flow control systems based on these new sensors. Finally, technology in nonlinear frequency conversion, UV laser materials, room-temperature mid-IR materials and broadly tunable multisection devices is reviewed to suggest new sensor possibilities.
The simple gas ethylene influences a diverse array of plant growth and developmental processes including germination, senescence, cell elongation, and fruit ripening. This review focuses on recent molecular genetic studies, principally in Arabidopsis, in which components of the ethylene response pathway have been identified. The isolation and characterization of two of these genes has revealed that ethylene sensing involves a protein kinase cascade. One of these genes encodes a protein with similarity to the ubiquitous Raf family of Ser/Thr protein kinases. A second gene shows similarity to the prokaryotic two-component histidine kinases and most likely encodes an ethylene receptor. Additional elements involved in ethylene signaling have only been identified genetically. The characterization of these genes and mutants will be discussed.
Although information has rapidly developed concerning the intracellular localization of plant proteins, relatively few reports concern the intracellular location of endo- and exo-proteolytic activities. Relatively few proteases have been purified, characterized, and associated with a specific cellular location. With the exception of the processing proteases involved in transport of proteins across membranes, little progress has yet been made concerning determination of in vivo products of specific proteases. Information on the turnover of individual proteins and the assessment of rate-limiting steps in pathways as proteins are turned over is steadily appearing. Since chloroplasts are the major site of both protein synthesis and, during senescence, degradation, it was important to show unambiguously that chloroplasts can degrade their own constituents. Another important contribution was to obtain evidence that the chloroplasts contain proteases capable of degrading their constituents. This work has been more tenuous because of the low activities found and the possibility of contamination by vacuolar enzymes during the isolation of organelles. The possible targeting of cytoplasmic proteins for degradation by facilitating their transport into vacuoles is a field which hopefully will develop more rapidly in the future. Information on targeting of proteins for degradation via the ubiquitin (Ub) degradation pathway is developing rapidly. Future research must determine how much unity exists across the different eukaryotic systems. At present, it has important implications for protein turnover in plants, since apparently Ub is involved in the degradation of phytochrome. Little information has been developed regarding what triggers increased proteolysis with the onset of senescence, although it appears to involve protein synthesis. Thus far, the evidence indicates that the complement of proteases prior to senescence is sufficient to carry out the observed protein degradation. This field of study has great practical implications, e.g. maintaining photosynthesis during seed-fill in order to obtain greater crop yields. The current use of stay green' variants in the populations of several crop plants to produce increased yields shows the potential for future development. The near future should see exciting discoveries in these areas of research that will have far reaching effects on the construction of transgenic plants for future research accomplishments and agricultural use.