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At least 973 records · Page 54Linked to original sources

In situ analysis of the organic framework in the prismatic layer of mollusc shell.

A novel in situ analytic approach was constructed by means of ion sputtering, decalcification and deprotein techniques combining with scanning electron microscopy (SEM) and transmission electron microscope (TEM) ultrastructural analysis. The method was employed to determine the spatial distribution of the organic framework outside and the inner crystal and organic/inorganic interface spatial geometrical relationship in the prismatic layer of cristaris plicate (leach). The results show that there is a substructure of organic matrix in the intracrystalline region. The prismatic layer forms according to strict hierarchical configuration of regular pattern. Each unit of organic template of prismatic layer can uniquely determine the column crystal growth direction, spatial orientation and size. Cavity templates are responsible for supporting. limiting size and shape and determining the crystal growth spatial orientation, while the intracrystal organic matrix is responsible for providing nucleation point and inducing the nucleation process of calcite. The stereo hierarchical fabrication of prismatic layer was elucidated for the first time.

Animals↗

Crystal structure of rat Bcl-xL. Implications for the function of the Bcl-2 protein family.

Bcl-xL is a member of the Bcl-2 protein family, which regulates apoptosis. Preparation of recombinant rat Bcl-xL yielded two forms, one deamidated at -Asn-Gly- sequences to produce isoaspartates and the other not deamidated. The crystal structures of the two forms show that they both adopt an essentially identical backbone structure which resembles the fold of human Bcl-xL: three layers of two alpha-helices each, capped at one end by two short helices. Both forms have a long disordered region, which contains the potential deamidation sites. The molecular structure exhibits a low level of interhelical interactions, the presence of three cavities, and a notable hydrophobic cleft surrounded by walls rich in basic residues. These unique structural features may be favorable for its accommodation into membranes or for possible rearrangement to modulate homo-/heterodimerization. Homology modeling of Bcl-2 and Bax, based on the Bcl-xL structure, suggests that Bax has the strongest potential for membrane insertion. Furthermore, we found a possible interface for interaction with non-Bcl-2 family member proteins, such as CED-4 homologues.

Animals↗

Structure of aldolase from Thermus thermophilus HB8 showing the contribution of oligomeric state to thermostability.

2-Deoxyribose-5-phosphate aldolase catalyzes a reversible aldol condensation of two aldehydes via formation of a covalent Schiff-base intermediate at the active lysine residue. The crystal structure of 2-deoxyribose-5-phosphate aldolase from Thermus thermophilus HB8 has been determined with and without the substrate at atomic resolution. This enzyme, which has a unique homotetramer structure, has been compared with the previously reported crystal structures of two orthologues from Escherichia coli and Aeropyrum pernix. In contrast to the similar alpha/beta-barrel fold of the monomers, substantial quaternary structural differences are observed between these three enzymes. Further comparison of the subunit-subunit interface areas of these aldolases showed a clear positive correlation between the interface area and the living temperature of the source organism. From these results, it is concluded that the oligomeric state of 2-deoxyribose-5-phosphate aldolase is important for the thermostability and not for the catalytic function.

Aeropyrum↗

Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function.

The nonclassical class I MHC molecule HLA-G is selectively expressed on extravillous cytotrophoblast cells at the maternal-fetal interface during pregnancy. HLA-G can inhibit the killing mediated by NK cells via interaction with the inhibitory NK cell receptor, leukocyte Ig-like receptor-1 (LIR-1). Comparison of the sequence of the HLA-G molecule to other class I MHC proteins revealed two unique cysteine residues located in positions 42 and 147. Mutating these cysteine residues resulted in a dramatic decrease in LIR-1 Ig binding. Accordingly, the mutated HLA-G transfectants were less effective in the inhibition of NK killing and RBL/LIR-1 induced serotonin release. Immunoprecipitation experiments demonstrated the involvement of the cysteine residues in the formation of HLA-G protein oligomers on the cell surface. The cysteine residue located at position 42 is shown to be critical for the expression of such complexes. These oligomers, unique among the class I MHC proteins, probably bind to LIR-1 with increased avidity, resulting in an enhanced inhibitory function of LIR-1 and an impaired killing function of NK cells.

Amino Acid Sequence↗

E-prescribing hits the medical world: what physicians need to know to get the right technology.

Electronic prescribing is an emerging technology that allows physicians to write appropriate, legible, and safe prescriptions quickly and easily, using a handheld computer unit linked to their office computer. The early physician adapters using this innovation had little objective information upon which to base their choice, so cost was their main criterion. Now, a variety of vendors and options are available, so the discriminating physician is able to select the electronic prescribing system most complementary to his or her practice's needs and unique style.

Clinical Pharmacy Information Systems↗

Water and cellular folding processes.

Proteins require a unique, native structure to perform their functions. Water molecules play an important role to develop and maintain this three-dimensional structure. Water is also necessary for several forms of enzyme catalysis, and is a constituent of many protein-protein, protein-DNA, or protein-RNA interfaces. Larger proteins acquire their native structure in a complicated folding pathway having several folding traps. Recent data indicated a key role of water molecules in this process. Protein flexibility, structural rearrangements, conformational transitions all require the fluctuating changes in hydrogen bond structure provided by interacting water molecules. Besides proteins, RNA and DNA structure is also heavily influenced by the presence of water. This review summarizes the important aspects of these fields, and draws attention to several open questions and hypotheses.

Cells↗

Primate anterior cingulate cortex: where motor control, drive and cognition interface.

Controversy surrounds the function of the anterior cingulate cortex. Recent discussions about its role in behavioural control have centred on three main issues: its involvement in motor control, its proposed role in cognition and its relationship with the arousal/drive state of the organism. I argue that the overlap of these three domains is key to distinguishing the anterior cingulate cortex from other frontal regions, placing it in a unique position to translate intentions to actions.

Animals↗

Osteocytes: a proposed multifunctional bone cell.

Most cell types are ascribed a single function. The osteoclast holds the unique distinction of performing only one function in the body - that of resorbing bone. The osteoblast has been ascribed the major function of bone matrix production. Other less well-defined cell types include progenitor cells and the nebulous cell type that can support osteoclast formation upon stimulation with various bone resorbing cytokines. Obviously, these cells could have other functions. The definition of an osteocyte is descriptive of its location - cells surrounded by mineralized matrix - not its function. For this year's Sun Valley Workshop on osteocytes, several proposed functions will be presented. First, a general consensus exists that osteocytes are most likely sensitive to mechanotransduction and translate mechanical strain into biochemical signals. Consensus does not exist on the nature of the mechanical strain, the form of the biochemical signals, the target cell(s), or the viability status of the osteocyte. Second, it is also proposed that this cell is incredibly adaptable and expresses plasticity in response to mechanical stimuli. In other words, this cell can readjust its responses to strain in the presence of other bone agents such as hormones and bone factors. Third, it will also be presented that osteocytes maintain systemic mineral homeostasis by regulating mineral release and deposition over the enormous surface area over which these cells interface with the surrounding matrix. Although osteocytes are terminally differentiated osteoblasts, they appear to have separate and distinct properties from their predecessors. Bone cell biologists loaded with an arsenal of bone anabolic and catabolic factors are examining the expression and effects of these factors on osteocytes. Engineers trained in mathematical modeling have generated new models of strain and connectivity to be tested. The unique morphology of osteocytes suggests that the cytoskeleton in these cells may function differently from osteoblasts and other cell types. Osteocytes may consist of different subpopulations; some that possess receptors for parathyroid hormone (PTH) and others that only express receptors for carboxyl terminal PTH suggesting different functions and responses. Osteocytes may respond rapidly to strain through glutamate receptor-like mechanisms, through calcium influxes, through gap junctions, and less rapidly through the production of small molecules and factors. Strain may take the form of substrate stretching and/or fluid flow. Osteocytes may communicate with other osteocytes and/or bone surface cells such as lining cells, stromal cells, osteoblasts, and/or osteoclasts and their precursors. The viability status of the osteocyte may determine the type of signals sent from these cells. If the cells are deprived of oxygen or nutrients, the apoptotic cells may send signals for initiation of resorption. If the cells and/or their dendritic process are ripped or torn by microdamage, they may send signals of both resorption and formation. If the majority of these theories are correct, then the osteocyte is the 'smart' cell that can direct or orchestrate the bone resorbing and bone forming cells even in its death and dying.

Journal Article↗

Gap junctions containing alpha8-connexin (MP70) in the adult mammalian lens epithelium suggests a re-evaluation of its role in the lens.

A missense mutation in one of the three lens connexins, alpha8-connexin, has been recently shown to be the genetic basis of the zonular pulverant lens cataract. This connexin had been considered to be expressed only in lens fibre cells. The present studies show that alpha8-connexin is also expressed in the lens epithelial cell layer. For this study, the distribution of gap junctions in the adult bovine lens has been investigated by confocal immunofluorescence microscopy using antibodies against alpha8-connexin (MP70) and alpha1-connexin (Cx43). In addition to the anticipated localisation of alpha8-connexin to the broad faces of lens fibre cells as reported in other species, alpha8-connexin was also found colocalized with alpha1-connexin at plaques in the lateral epithelial-epithelial plasma membranes of the bovine lens. These data suggest that mixed alpha8-connexin/alpha1-connexin plaques are between epithelial cells at their apico-lateral plasma membranes, rather than between epithelial and fibre cells. Indeed, freeze fracture analyses of the epithelial-fibre cell interface failed to reveal gap junctions connecting the epithelium and the underlying fibre cells. Importantly, microdissection and subsequent immunoblotting of lens epithelium samples confirmed the immunolocalisation results. The data suggest mature mammalian lens epithelial cells could form either heteromeric, heterotypic and/or mixed homomeric-homotypic gap junctional complexes with unique physiological properties, an important point when considering the role of epithelial cell connexins in cataractogenesis.

Animals↗

AA.AG@helix.ends: A:A and A:G base-pairs at the ends of 16 S and 23 S rRNA helices.

This study reveals that AA and AG oppositions occur frequently at the ends of helices in RNA crystal and NMR structures in the PDB database and in the 16 S and 23 S rRNA comparative structure models, with the G usually 3' to the helix for the AG oppositions. In addition, these oppositions are frequently base-paired and usually in the sheared conformation, although other conformations are present in NMR and crystal structures. These A:A and A:G base-pairs are present in a variety of structural environments, including GNRA tetraloops, E and E-like loops, interfaced between two helices that are coaxially stacked, tandem G:A base-pairs, U-turns, and adenosine platforms. Finally, given structural studies that reveal conformational rearrangements occurring in regions of the RNA with AA and AG oppositions at the ends of helices, we suggest that these conformationally unique helix extensions might be associated with functionally important structural rearrangements.

Base Pairing↗

Rpb4 and Rpb7: subunits of RNA polymerase II and beyond.

RNA Polymerase II (pol II) is a large multi-subunit complex that is responsible for the synthesis of all eukaryotic mRNAs. Its correct and timely recruitment to promoter regions is a crucial step of transcription regulation, involving complicated and well-controlled networks of protein-DNA and protein-protein interactions. The best-studied pol II is the yeast complex consisting of 12 subunits (Rpb1-12). Rpb4 and Rpb7 form a dissociable heterodimer (Rpb4/7). The unique location of Rpb4/7 within the transcription initiation complex, and its capacity to interact with various transcription factors, suggest that it provides important links to the network of interactions that control transcription initiation. Moreover, Rpb4/7 executes some non-transcriptional activities, including mRNA transport. Hence, Rpb4/7 functions at the interface of transcriptional and post-transcriptional machinery.

Animals↗

Source of the ice-binding specificity of antifreeze protein type I.

Antifreeze proteins (AFPs) are a group of structurally very diverse proteins with the unique capability of binding to the surface of seed ice crystals and inhibiting ice crystal growth. The AFPs bind with high affinity to specific planes of the ice crystal. Previously, this affinity of AFPs has been ascribed to the formation of multiple hydrogen bonds across the protein-ice interface, but more recently van der Waals interactions have been suggested to be the dominant energetic factors for the adsorption. To determine whether van der Waals interactions are also responsible for the binding specificities of AFPs, the protein-ice interaction of the helical AFP Type I from winter flounder (HPLC6) was studied using a Monte Carlo rigid body docking approach. HPLC6 binds in the [1102] direction of the [2021] plane, with the Thr-Ala-Asn surface comprising the protein's binding face. The binding of HPLC6 to this ice plane is highly preferred, but the protein is also found to bind favorably to the [1010] prism plane using a different protein surface comprised of Thr and Ala residues. The results show that van der Waals interactions, despite accounting for most of the intermolecular energy (>80%), are not sufficient to completely explain the AFP binding specificity.

Algorithms↗

Fetal and neonatal gene therapy: benefits and pitfalls.

The current approaches to gene therapy of monogenetic diseases into mature organisms are confronted with several problems including the following: (1) the underlying genetic defect may have already caused irreversible pathological changes; (2) the level of sufficient protein expression to ameliorate or prevent the disease requires prohibitively large amounts of gene delivery vector; (3) adult tissues may be poorly infected by conventional vector systems dependent upon cellular proliferation for optimal infection, for example, oncoretrovirus vectors; (4) immune responses, either pre-existing or developing following vector delivery, may rapidly eliminate transgenic protein expression and prevent future effective intervention. Early gene transfer, in the neonatal or even fetal period, may overcome some or all of these obstacles. The mammalian fetus enjoys a uniquely protected environment in the womb, bathed in a biochemically and physically supportive fluid devoid of myriad extra-uterine pathogens. Strong physical and chemical barriers to infection might, perhaps, impede the frenetic cell division. The physical support and the biochemical support provided by the fetal-maternal placental interface may, therefore, minimize the onset of genetic diseases manifest early in life. The fetal organism must prepare itself for birth, but lacking a mature adaptive immune system may depend upon more primordial immune defences. It is the nature of these defences, and the vulnerabilities they protect, that are poorly understood in the context of gene therapy and might provide useful information for approaches to gene therapy in the young, as well as perhaps the mature organism.

Animals↗

Development and evaluation of a quantitative video-fluorescence imaging system and fluorescent tracer for measuring transfer of pesticide residues from surfaces to hands with repeated contacts.

A video imaging system and the associated quantification methods have been developed for measurement of the transfer of a fluorescent tracer from surfaces to hands. The highly fluorescent compound riboflavin (vitamin B2), which is also water soluble and non-toxic, was chosen as the tracer compound to simulate the transfer from surfaces to hands of pesticide residues deposited on carpeted and laminate surfaces of a residence. The system was designed around the unique properties of riboflavin. Excitation energy was centered near 440 nm (in the blue region of the visible spectrum); emitted energy was measured at 600 nm (in the red/orange region), well beyond the significant fluorescence peak maximum of natural skin. A video camera system with an image intensifier was interfaced to an image processing analysis software system. Quantification utilized chemometric techniques to account for the non-linearity of pixel detectivity and non-linear excitation strength. Method quantification and detection limits were approximately 0.1 and 0.02 micro g/cm(2), respectively. The relative error was approximately 100% at the quantification limit, but <20% at higher levels. Transfer of riboflavin to hands, resulting in dermal loadings in the range 0.1-2.0 micro g/cm(2), were measured with this system from surfaces whose loadings approximated the pesticide levels that occur in homes after broadcast application.

Calibration↗

Clinical implications of adult developmental theory.

Multidisciplinary studies of adulthood have revolutionized thinking about developmental processes during the second half of life. These ideas are just beginning to be integrated with clinical theory and practice. The elaboration of the interface between the rapidly expanding developmental theory of normal adulthood and clinical intervention with older patients is a psychiatric frontier. Illustrating with clinical examples, the authors offer a rationale for using new diagnostic tools, suggest a revision of the theory of transference to include sources beyond childhood, and describe unique transference paradigms in older patients as well as equally phase-specific countertransference responses in their therapists.

Adult↗

DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology.

Dendritic cells (DC) are present in essentially every tissue where they operate at the interface of innate and acquired immunity by recognizing pathogens and presenting pathogen-derived peptides to T cells. It is becoming clear that not all C-type lectins on DC serve as antigen receptors recognizing pathogens through carbohydrate structures. The C-type lectin DC-SIGN is unique in that it regulates adhesion processes, such as DC trafficking and T-cell synapse formation, as well as antigen capture. Moreover, even though several C-type lectins have been shown to bind HIV-1, DC-SIGN does not only capture HIV-1 but also protects it in early endosomes allowing HIV-1 transport by DC to lymphoid tissues, where it enhances trans infection of T cells. Here we discuss the carbohydrate/protein recognition profile and other features of DC-SIGN that contribute to the potency of DC to control immunity.

Animals↗

A randomized controlled trial of automated term composition.

OBJECTIVE: To compare the ability of an Automated Term Composition (ATC) algorithm with non-compositional mappings to provide coverage (exact mappings to a controlled vocabulary) for a randomly selected set of free text entries which were entered as headings to the Impression section of the clinical notes system at the Mayo Foundation. We also compare the results of four evaluators to determine the inter-observer variability and the variance between term sets, with respect to the accuracy of the mappings and the reliability of the failure analysis. METHODS: From a corpus of approximately 1,000,000 unique terms entered into the Impression/Report/Plan section of the clinical notes system in the calendar year 1997, we randomly selected 1,000 terms. We then further randomized these 1,000 terms into two groups of 500 (Sets A and B). We constructed two copies of the same term matching interface, one without ATC (alpha) and one with ATC (beta). We took four expert Indexers and assigned them to one of the following tasks. The first reviewer (R1) compared set A using the alpha program and then set B using the beta program (R1(Aalpha + Bbeta)). The second compared set A using the alpha program and then set B using the alpha program (R2(A + B) alpha). The third compared set B using the beta program and then set A using the beta program (R3(B + A) beta). The fourth compared set A using the beta program and then set B using the alpha program (R4(Abeta + Balpha)). RESULTS: The program with Automated Term Composition mapped 540 out of the 1,000 Concepts correctly (54.0%). The same program without ATC mapped only 276 out of the 1,000 Concepts correctly (27.6%). Therefore the program with ATC was significantly more effective at matching concepts in our problem lists than the same search engine without ATC (p < 0.0001; McNemar Method). These figures result from the comparison of the alpha program with the beta program by reviewers one and four. Failure analysis showed that with the alpha version 425 out of the 724 mismatches were because a base concept was missing from the retrieval set (58.7%) and 299 mismatches were from missing qualifiers or modifiers or both (41.3%). In the beta version of the program (with ATC) 340 out of the 460 mismatches were secondary to there being a missing base concept in the retrieval set (73.9%) and only 120 mismatches due to missing modifiers and or qualifiers (26.1%). CONCLUSIONS: Automated term composition provided significantly better coverage of a randomly chosen set of patient problems, diagnosed at the Mayo Clinic during the 1997 calendar year, when compared with the same information retrieval system without ATC. We believe that these results speak further to the excellent content coverage provided by the UMLS metathesaurus. These authors believe that increased structure, normalization of UMLS content and semantics, and better tools to make use of the currently available content such as automated term composition, are what is needed to leverage the production of commercially viable tools that provide access to controlled vocabularies for medicine.

Abstracting and Indexing↗

Remote access into your computer network.

In an effort to help summarize all of this information, let's break it down into 2 groups: dynamic IP and static IP. Static IP is simple--they all work well if you have an external static IP address. Now the fun part--dynamic IP. GoToMyPC, PCAnywhere, VNC (note: not secure), and RWW will all work with a dynamic IP address. So, what is the best solution for your dynamic IP scenario? My affirmative, steadfast answer is... it depends. It depends on your unique network, access requirements, cost, and willingness to use other tools to make the solution work effectively.

Computer Communication Networks↗