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PubMed1998

The activities of acidic and glutamine-rich transcriptional activation domains in plant cells: design of modular transcription factors for high-level expression.

The aim of this work was to design strong transcriptional activators that can be used to regulate plant gene expression. The contribution of different components in a transcription factor and target gene system was assayed by measuring transcriptional activation. Each component was optimised to achieve maximal reporter gene expression in transient protoplast transformation assays. The DNA-binding domain of the yeast transcriptional activator GAL4 was studied in the context of fusion proteins with activation domains of the herpes simplex virus protein VP16 or the tomato Myb-like activator THM18. Multimerisation of the activation domain and insertion of a homopolymeric glutamine stretch was used to increase transcription factor potency. Evidence is presented that these modifications can result in even more active transcription factors when they are combined. Finally, it was demonstrated using competition experiments that transcription factors with acidic activation domains can mutually suppress their activation potentials when expressed at high levels.

Base Sequence↗
PubMed2000

Sequential assignment of proline-rich regions in proteins: application to modular binding domain complexes.

Many protein-protein interactions involve amino acid sequences containing proline-rich motifs and even polyproline stretches. The lack of amide protons in such regions complicates assignment, since 1HN-based triple-resonance assignment strategies cannot be employed. Two such systems that we are currently studying include an SH2 domain from the protein Crk with a region containing 9 prolines in a 14 amino acid sequence, as well as a WW domain that interacts with a proline-rich target. A modified version of the HACAN pulse scheme, originally described by Bax and co-workers [Wang et al. (1995) J. Biomol. NMR, 5, 376-382], and an experiment which correlates the intra-residue 1Halpha, 13Calpha/13Cbeta chemical shifts with the 15N shift of the subsequent residue are presented and applied to the two systems listed above, allowing sequential assignment of the molecules.

Amino Acid Sequence↗
PubMed2001

Modular organization of the AIDA autotransporter translocator: the N-terminal beta1-domain is surface-exposed and stabilizes the transmembrane beta2-domain.

The adhesin involved in diffuse adherence (AIDA-I) of the diarrhoeagenic Escherichia coli strain 2787 (O126:H27) is synthesized as a precursor molecule. This pre-pro-protein is N- and C-terminally processed to generate three distinct domains, which are characteristic for autotransporter secretion systems in Gram-negative bacteria: the N-terminal pre-peptide, the alpha-domain and the C-terminal beta-domain. The outer membrane-integrated beta-domain (AIDAC) is responsible for the surface-presentation of the alpha-domain (AIDA-I) and is thus termed 'translocator'. Characterization of extracted N-terminally truncated forms and of in vitro refolded proteins revealed a core structure at the C-terminus of the translocator which was found to be very stable even in the presence of SDS. Denaturation occurs only after additional incubation at temperatures above 80 degrees C. Reporter-epitope insertions were used to analyze the location of regions of membrane-integrated AIDAC relative to the membrane. The modified topological model developed for the AIDA translocator suggests the N-terminal domain (beta1) encompasses approximately 10 kDa to represent a completely surface-exposed segment while the C-terminal compact core domain (beta2) remains integrated in the membrane as a beta-barrel-like structure. Though the beta2-core structure alone harbours all the information for the outer membrane integration of AIDAC it is additionally stabilized by the beta1-domain. Access to large amounts of complete as well as truncated AIDAC proteins facilitated the study of protein folding by CD and fluorescence spectroscopy. A potential pore forming activity of the translocator using the completely refolded AIDAC or the beta2-core in black-lipid membranes could not be demonstrated.

Adhesins, Escherichia coli↗
PubMed2001

Acceptability of a new modular protein substitute for the dietary treatment of phenylketonuria.

The major source of protein in the dietary treatment of phenylketonuria(PKU) is a phenylalanine-free amino acid mixture. Traditionally, these medical products have also contained other nutrients and have been in powder form. However, their disagreeable taste and odour, the large volume required to provide sufficient protein and the inconvenience of their preparation and storage have hindered compliance with consumption among adolescents and adults. We studied the acceptability of a new medical product for the treatment of PKU. This product, Phlexy-10 (SHS North America, Gaithersburg, MD, USA), is available in three forms: sachets of premeasured powder to be constituted as a drink, fruit-flavoured bars and prefilled capsules. A vitamin-mineral mixture is separately provided. The forms are interchangeable because each component (one sachet, one bar or 20 capsules) provides 10g of amino acids. Since the product is primarily a source of amino acids, protein requirements can be met using a smaller volume than with traditional medical products. Eleven subjects enrolled in a 24-week trial that included clinical and laboratory evaluations. Nine subjects completed the study and 8 remained on the Phlexy-10 after the study. The powder drink was the favourite module used. One-third of the subjects included the bars and another third included the capsules in their regimens. The vitamin-mineral mixture was the least acceptable component. Mean weekly blood phenylalanine decreased by 40% from mean baseline levels. Blood concentrations of vitamins and minerals were normal except for a low zinc concentration in two subjects and a low vitamin B12 concentration in another. The lower caloric content and the separate vitamin-mineral mixture require careful monitoring of these nutrients. Phlexy-10 appears to be an adequate medical product for the treatment of PKU. Its convenience, flexibility of form and improved taste are appealing to many individuals on diet for PKU.

Adolescent↗
PubMed2002

Titin as a modular spring: emerging mechanisms for elasticity control by titin in cardiac physiology and pathophysiology.

Titin is a giant elastic protein that functions as a molecular spring that develops passive muscle stiffness. Here we discuss the molecular basis of titin's extensibility, how titin's contribution to passive muscle stiffness may be adjusted and how adjustment of titin's stiffness may influence muscle contraction. We also focus on ligands that link titin to membrane channel activity, protein turnover and gene expression.

Animals↗
PubMed2002

AmpA, a modular protein containing disintegrin and ornatin domains, has multiple effects on cell adhesion and cell fate specification.

Proteins containing disintegrin domains play a variety of roles in regulating processes involving adhesion, migration and cell type specification during development of many metazoan organisms. Most disintegrin domain containing proteins belong to the ADAM (a disintegrin and a metalloprotease) family of proteins that also contain a metalloprotease domain. Here we describe a small secreted protein from Dictyostelium that contains multiple repeated domains sharing homology with both the disintegrin motif and with a second class of fibrinogen receptor antagonists, the ornatins. This protein, called AmpA for its role in modulating adhesion, differs from the ADAM family proteins in that it lacks a metalloprotease domain. Nonetheless, it appears to be involved in the same complex spectrum of developmental functions as the metazoan ADAM family proteins. Here we review the structure and evolution of this protein and its function in cell adhesion and cell type specification. We discuss possible mechanisms by which it might function and review the emerging evidence for a close coupling between cell adhesion and cell type specification.

Amino Acid Sequence↗
PubMed2004

Assessment of wear on the cones of modular stainless steel Exeter hip stems.

The wear on the stem cones of retrieved Exeter Universal hip stems has been assessed using scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDX) and surface profilometry. The in-service life of these prosthetic stems varied, up to a maximum of 7 years. A combination of SEM, EDX and visual assessment indicates that the stem cones have not suffered from any corrosion. SEM scans indicate that damage to stem cones (excluding extraction and post-removal damage) can be categorised into insertion marks and fretting marks. In some cases there are signs of material being deposited on the cone surface. Surface profilometry suggests that the levels of debris generation at the cone/internal head interface are very low relative to those that are likely to be associated with head articulation against the acetabular cup. A total of 20 stem cones underwent SEM scans. From these, 10 subsequently have undergone surface profilometry along with the corresponding internal head surfaces. There is a good correlation between surface roughness measured by surface profilometry and the topography observed in the SEM images. The surface roughness of each stem cone is similar to that of the corresponding internal head surface.

Arthroplasty, Replacement, Hip↗
PubMed1999

[Modular nursing system in pediatric ambulatory care according to nursing insurance legislation XI].

UNLABELLED: In the compulsory nursing insurance according to German legislation, the assessed degree of disablement in children is dependent on their daily quantitative need for nursing care with respect to 19 distinctive items belonging to the four sectors "personal hygiene", "mobility", "nutrition", and "household duties", that exceeds normal age-dependent requirements. In ambulatory nursing, exactly that care is given to the clients. OBJECTIVE: Are there typical combinations of items scoring positively, delivering the basis for a simplified billing schedule? DESIGN AND METHODS: 4500 records from the expert assessment of children < 18 years underwent a hierarchical cluster analysis (SPSS, Ward's method). RESULTS: The resulting dendrogram revealed distinct relationships between items. The items clustered into 4 main groups. Each cluster comprised items with a common thematic relationship (A = household duties, B = mobility, C = personal hygiene, D = nutrition/leaving one's home--scoring positively may indicate extra severe disablement). CONCLUSION: Remarkably enough, the resulting four clusters are very similar to the four sectors as defined by legislation (see above), although each single item is assessed independently. Our results are similar to that found in adults (Michel et al., 1998). Here we deliver the statistical basis for a modularised system of ambulatory paediatric nursing care, or its costing.

Activities of Daily Living↗
PubMed2002

4.3 Towards a global superstore of quality-assured modularized learning programmes.

Our section's assignment entails exploration of the current challenges to develop criteria for quality assurance of dental e-learning material. Our work has involved comparison of current methods of assessment, the identification of best practice and the formulation of guidelines and criteria for producers and assessors. We anticipate the need for a standing international body responsible for the revision and refinement of guidelines and criteria and that might award a 'Seal of Approval'.

Computer-Assisted Instruction↗
PubMed2002

Modular extracorporeal life support for multiorgan failure patients.

Adults receiving respiratory Extracorporeal Membrane Oxygenation (ECMO) have 66% survival. Nonsurvivors develop multisystem organ failure (MSOF). Once hepatic failure develops, death usually follows shortly. Serum bilirubin > 300 micromol/l predicted death with 87.8% sensitivity and 90.3% specificity in 41 adults who received ECMO in our institution during 1998 and 1999. No patients survive with a peak bilirubin > 400 micromol/l. The Molecular Adsorbent Recirculating System (MARS) is a cell-free extracorporeal liver support device; we hypothesized that using MARS in adult respiratory ECMO patients with a bilirubin >300 micromol/l could improve survival in MSOF. The MARS was used in five such patients aged 19-56 who developed liver failure secondary to a respiratory illness. Mean peak bilirubin was 529 micromol/l and the lowest peak bilirubin was 436 micromol/l. Patients received between 1 and 8 MARS treatments, mean reduction in serum bilirubin for each patient ranging between 30 and 162 micromol/l. Two of five patients survived (40%), survivors showing the greatest reduction in serum bilirubin in response to MARS. All patients would have been expected to die according to our previous experience. We believe that MARS may prove a useful therapy for patients with MSOF.

Adult↗
PubMed2003

Modularity as a fish (Xenotoca eiseni) views it: conjoining geometric and nongeometric information for spatial reorientation.

When disoriented in a closed rectangular tank, fish (Xenotoca eiseni) reoriented in accord with the large-scale shape of the environment, but they were also able to conjoin geometric information with nongeometric properties such as the color of a wall or the features provided by panels located at the corners of the tank. Fish encoded geometric information even when featural information sufficed to solve the spatial task. When tested after transformations that altered the original arrangement of the panels, fish were more affected by those transformations that modified the geometric relationship between the target and the shape of the environment. Finally, fish appeared unable to use nongeometric information provided by distant panels. These findings show that a reorientation mechanism based on geometry is widespread among vertebrates, though the joint use of geometric and nongeometric cues by fish suggest that the degree of information encapsulation of the mechanism varies considerably between species.

Animals↗
PubMed2006

Functional modularity of the medial prefrontal cortex: involvement in human empathy.

To investigate medial frontal lobe mediation of human empathy, the authors analyzed the activation areas in statistical parametric maps of 80 studies reporting neural correlates of empathic processing. The meta-analysis revealed 6 spatially distinct activation clusters in the medial part of the frontal lobe dorsal to the intercommissural plane. The most dorsal cluster coincided with the left supplementary motor area (SMA). Rostrally adjacent was a cluster that overlapped with the right pre-SMA. In addition, there were 3 left-hemispheric and 1 right-hemispheric clusters located at the border between the superior frontal and anterior cingulate gyrus. A broad spectrum of cognitive functions were associated with these clusters, including attention to one's own action, which was related to activations in the SMA, and valuation of other people's behavior and ethical categories, which was related to activations in the most rostroventral cluster. These data complement the consistent observation that lesions of the medial prefrontal cortex interfere with a patient's perception of own bodily state, emotional judgments, and spontaneous behavior. The results of the current meta-analysis suggest the medial prefrontal cortex mediates human empathy by virtue of a number of distinctive processing nodes. In this way, the authors' findings suggest differentiated aspects of self-control of behavior.

Brain Injuries↗
PubMedDate not supplied

Modular arrangement of functional domains along the sequence of an aminoacyl tRNA synthetase.

Gene deletions show that much of Escherichia coli alanine tRNA synthetase is dispensable for each of three activities and that these activities appear to require specific domains arranged linearly along the polypeptide. Thus, variable fusions of extra polypeptide domains to a catalytic core may account for the diverse of aminoacyl tRNA synthetases.

Adenosine Triphosphate↗
PubMed1999

From molecular to modular cell biology.

Cellular functions, such as signal transmission, are carried out by 'modules' made up of many species of interacting molecules. Understanding how modules work has depended on combining phenomenological analysis with molecular studies. General principles that govern the structure and behaviour of modules may be discovered with help from synthetic sciences such as engineering and computer science, from stronger interactions between experiment and theory in cell biology, and from an appreciation of evolutionary constraints.

Action Potentials↗
PubMed1999

The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization.

The sterile alpha motif (SAM) domain is a novel protein module of approximately 70 amino acids that is found in a variety of signaling molecules including tyrosine and serine/threonine protein kinases, cytoplasmic scaffolding and adaptor proteins, regulators of lipid metabolism, and GTPases as well as members of the ETS family of transcription factors. The SAM domain can potentially function as a protein interaction module through the ability to homo- and hetero-oligomerize with other SAM domains. This functional property elicits the oncogenic activation of chimeric proteins arising from translocation of the SAM domain of TEL to coding regions of the betaPDGF receptor, Abl, JAK2 protein kinase and the AML1 transcription factor. Here we describe the 2.0 A X-ray crystal structure of a SAM domain homodimer from the intracellular region of the EphA4 receptor tyrosine kinase. The structure reveals a mode of dimerization that we predict is shared amongst the SAM domains of the Eph receptor tyrosine kinases and possibly other SAM domain containing proteins. These data indicate a mechanism through which an independently folding protein module can form homophilic complexes that regulate signaling events at the membrane and in the nucleus.

Amino Acid Sequence↗
PubMed1984

The modular organization of the pial arterial system in phylogeny.

We have investigated the pial arterial microcircles formed by the consecutive ramifications and anastomoses of minute pial vessels on the surface of the cerebral neocortex in various vertebrate species, representatives of various levels of phylogenic development. We found that the pial arterial microcircles became gradually more complex in the following order: hen less than rabbit less than cat less than dog less than monkey. The gradual development of microcircles involves various features in these species: They become formed predominantly of smaller pial arterial branches whose vasomotor activity is much higher as compared with that of the larger ones; each circle occupies a smaller area, and hence the number of circles per surface of neocortex increases; the density of arterial branches feeding the circles increases despite the smaller size of the latter; the number of off-shooting precortical and radial arteries penetrating the cortex increases; the areas of neocortex fed by individual radial arteries get gradually smaller. Thus, the development of the pial arterial bed contributes more and more toward precise spatial regulation of an adequate blood supply to increasingly smaller areas of neocortical tissue as we rise toward higher levels in phylogeny.

Animals↗