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At least 901 records · Page 50Linked to original sources
PubMed2002

The calmodulin-binding domain from a plant kinesin functions as a modular domain in conferring Ca2+-calmodulin regulation to animal plus- and minus-end kinesins.

Plant kinesin-like calmodulin-binding protein (KCBP) is a novel member of the kinesin superfamily that interacts with calmodulin (CaM) via its CaM-binding domain (CBD). Activated CaM (Ca(2+)-CaM) has been shown to inhibit KCBP interaction with microtubules (MTs) thereby abolishing its motor- and MT-dependent ATPase activities. To test whether the fusion of CBD to non-CaM-binding kinesins confers Ca(2+)-CaM regulation, we fused the CBD of KCBP to the N or C terminus of a minus-end (non-claret disjunction) or C terminus of a plus-end (Drosophila kinesin) motor. Purified chimeric kinesins bound CaM in a Ca(2+)-dependent manner whereas non-claret disjunction, Drosophila kinesin, and KCBP that lack a CBD did not. As in the case of KCBP with CBD, the interaction of chimeric motors with MTs, as well as their MT-stimulated ATPase activity, was inhibited by Ca(2+)-CaM. The presence of a spacer between the motor and CBD did not alter Ca(2+)-CaM regulation. However, KCBP interaction with MTs and its MT-stimulated ATPase activity were not inhibited when the motor domain and CBD were added separately, suggesting that Ca(2+)-CaM regulation of CaM-binding motors occurs only when the CBD is attached to the motor domain. These results show that the fusion of the CBD to animal motors confers Ca(2+)-CaM regulation and suggest that the CBD functions as a modular domain in disrupting motor-MT interaction. Our data also support the hypothesis that CaM-binding kinesins may have evolved by addition of a CBD to a kinesin motor domain.

Animals↗
PubMed2005

YxiN is a modular protein combining a DEx(D/H) core and a specific RNA-binding domain.

DEx(D/H) proteins, typically described as RNA helicases, participate in rearrangement of RNA-RNA and possibly RNA-protein complexes in the cell. Aside from the conserved DEx(D/H) core, members of this protein family often contain N- and C-terminal extensions that are responsible for additional functions. The Bacillus subtilis DEx(D/H)-box protein YxiN and its Escherichia coli ortholog DbpA contain an approximately 80 amino acid C-terminal extension that has been proposed to specifically interact with a region of 23 S ribosomal RNA including hairpin 92. In this study, the DEx(D/H)-box core and the C-terminal domain of YxiN were expressed and characterized as separate proteins. The isolated DEx(D/H)-box core, YxCat, had weak, nonspecific RNA binding activity and showed RNA-stimulated ATPase activity with a Km(ATP) that resembled several non-specific DEx(D/H) proteins. The isolated C-terminal domain, YxRBD, bound RNA with the high affinity and specificity seen with full-length YxiN. Thus, YxiN is a modular protein combining the activities of the YxCat and YxRBD domains. Footprinting of YxiN and YxRBD on a 172-nucleotide fragment of 23 S rRNA was used to identify the sites of interaction of the C-terminal and helicase domains with the RNA.

Adenosine Triphosphatases↗
PubMed2006

Modular structure of the receptor binding proteins of Lactococcus lactis phages. The RBP structure of the temperate phage TP901-1.

Lactococcus lactis is a gram-positive bacterium widely used by the dairy industry. Several industrial L. lactis strains are sensitive to various distinct bacteriophages. Most of them belong to the Siphoviridae family and comprise several species, among which the 936 and P335 are prominent. Members of these two phage species recognize their hosts through the interaction of their receptor-binding protein (RBP) with external cell wall saccharidices of the host, the "receptors." We report here the 1.65 A resolution crystal structure of the RBP from phage TP901-1, a member of the P335 species. This RBP of 163 amino acids is a homotrimer comprising three domains: a helical N terminus, an interlaced beta-prism, and a beta-barrel, the head domain (residues 64-163), which binds a glycerol molecule. Fluorescence quenching experiments indicated that the RBP exhibits high affinity for glycerol, muramyl-dipeptide, and other saccharides in solution. The structural comparison of this RBP with that of lactococcal phage p2 RBP, a member of the 936 species (Spinelli, S., Desmyter, A., Verrips, C. T., de Haard, J. W., Moineau, S., and Cambillau, C. (2006) Nat. Struct. Mol. Biol. 13, 85-89) suggests a large extent of modularity in RBPs of lactococcal phages.

Amino Acid Sequence↗
PubMed2006

Ribonucleotide reductase modularity: Atypical duplication of the ATP-cone domain in Pseudomonas aeruginosa.

The opportunistic pathogen Pseudomonas aeruginosa, which causes serious nosocomial infections, is a gamma-proteobacterium that can live in many different environments. Interestingly P. aeruginosa encodes three ribonucleotide reductases (RNRs) that all differ from other well known RNRs. The RNR enzymes are central for de novo synthesis of deoxyribonucleotides and essential to all living cells. The RNR of this study (class Ia) is a complex of the NrdA protein harboring the active site and the allosteric sites and the NrdB protein harboring a tyrosyl radical necessary to initiate catalysis. P. aeruginosa NrdA contains an atypical duplication of the N-terminal ATP-cone, an allosteric domain that can bind either ATP or dATP and regulates the overall enzyme activity. Here we characterized the wild type NrdA and two truncated NrdA variants with precise N-terminal deletions. The N-terminal ATP-cone (ATP-c1) is allosterically functional, whereas the internal ATP-cone lacks allosteric activity. The P. aeruginosa NrdB is also atypical with an unusually short lived tyrosyl radical, which is efficiently regenerated in presence of oxygen as the iron ions remain tightly bound to the protein. The P. aeruginosa wild type NrdA and NrdB proteins form an extraordinarily tight complex with a suggested alpha4beta4 composition. An alpha2beta2 composition is suggested for the complex of truncated NrdA (lacking ATP-c1) and wild type NrdB. Duplication or triplication of the ATP-cone is found in some other bacterial class Ia RNRs. We suggest that protein modularity built on the common catalytic core of all RNRs plays an important role in class diversification within the RNR family.

Adenosine Triphosphate↗
PubMed2007

Neuronal apoptotic signaling pathways probed and intervened by synthetically and modularly modified (SMM) chemokines.

As the main coreceptors for human immunodeficiency virus type 1 (HIV-1) entry, CXCR4 and CCR5 play important roles in HIV-associated dementia (HAD). HIV-1 glycoprotein gp120 contributes to HAD by causing neuronal damage and death, either directly by triggering apoptotic pathways or indirectly by stimulating glial cells to release neurotoxins. Here, to understand the mechanism of CXCR4 or CCR5 signaling in neuronal apoptosis associated with HAD, we have applied synthetically and modularly modified (SMM)-chemokine analogs derived from natural stromal cell-derived factor-1alpha or viral macrophage inflammatory protein-II as chemical probes of the mechanism(s) whereby these SMM-chemokines prevent or promote neuronal apoptosis. We show that inherently neurotoxic natural ligands of CXCR4, such as stromal cell-derived factor-1alpha or viral macrophage inflammatory protein-II, can be modified to protect neurons from apoptosis induced by CXCR4-preferring gp120(IIIB), and that the inhibition of CCR5 by antagonist SMM-chemokines, unlike neuroprotective CCR5 natural ligands, leads to neurotoxicity by activating a p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Furthermore, we discover distinct signaling pathways activated by different chemokine ligands that are either natural agonists or synthetic antagonists, thus demonstrating a chemical biology strategy of using chemically engineered inhibitors of chemokine receptors to study the signaling mechanism of neuronal apoptosis and survival.

AIDS Dementia Complex↗
PubMed2003

Physical and functional modularity of the protein network in yeast.

While protein-protein interactions have been studied largely as a network graph without physicality, here we analyze two protein complex data sets of Saccharomyces cerevisiae to relate physical and functional modularity to the network topology. We study for the first time the number of different protein complexes as a function of the protein complex size and find that it follows an exponential decay with a characteristic number of about 7. This reflects the dynamics of complex formation and dissociation in the cell. The analysis of the protein usage by complexes shows an extensive sharing of subunits that is due to the particular organization of the proteome into physical complexes and functional modules. This promiscuity accounts for the high clustering in the protein net-work graph. Our results underscore the need to include the information contained in observed protein complexes into protein network analyses.

Models, Theoretical↗
PubMed2001

Stump lengthening after hip disarticulation using a modular endoprosthesis in 5 patients.

To reduce the disability after hip disarticulation, we developed a special surgical procedure in patients having a proximal femoral tumor with a large tumor involving the sciatic nerve or neoplasms involving the tibia and femur. The hip was disarticulated, but we preserved a musculocutaneous flap. A modular endoprosthesis was then placed in the acetabulum or, in case of an extraarticular resection of the hip joint, it was placed in the iliac bone. A trevira tube was used for reconstruction of the joint capsule and fixation of soft tissues. We performed this procedure in 5 patients who had a good functional outcome.

Adolescent↗
PubMed1995

Linguistic processes in the two cerebral hemispheres: implications for modularity vs interactionism.

Three experiments are reported on lexical decision to target stimuli presented to the right or left visual field (RVF, LVF) following a variety of priming stimuli, words, incomplete sentences, and scrambled sentences. Lexical decision performance is always superior for stimuli presented to the RVF. Primes always facilitate the discrimination of words from nonword target stimuli presented to either visual field. However, when the prime is a sentence which is completed syntactically and semantically by a target word (normal, congruent sentence), the facilitation for RVF presented targets is significantly greater than for LVF targets. When the prime is either: (1) a single word, (2) a nonstructured (scrambled) sentence, or (3) a noncongruent-related sentence, the difference in facilitation between RVF and LVF presented targets is much smaller. These data are discussed with respect to (1) the nature of priming by sentences versus words, (2) language processing by the two hemispheres, and (3) modularity versus interactionism in language processing.

Adult↗
PubMed1995

Recovered consciousness: a hypothesis concerning modularity and episodic memory.

Why should conscious recollection be associated with recovery of some memories and not others? A hypothesis is proposed and defended that the medial temporal lobe/hippocampal complex (MTL/H) and related limbic structures comprise a memory module that receives as its input only information that is consciously apprehended. The module then binds or conjoins into memory traces those neural elements that mediated the conscious experience so that effectively "consciousness" is as intergral a part of the memory traces as it was during the experience of the event. When memory traces are retrieved, what is recovered are the phenomenological records (Conway, 1992) of experienced events which are integrated content-consciousness packets. Evidence is presented which suggests that the MTL/H module satisfies Fodorian criteria of modularity. The MTL/H module is compared to perceptual modules in nonfrontal neocortex that mediate performance on tests of memory without awareness and to prefrontal neocortex that acts as a central working-with-memory system that operates on the input to MTL/H and the shallow output from it.

Animals↗
PubMed1995

Double dissociation without modularity: evidence from connectionist neuropsychology.

Many theorists assume that the cognitive system is composed of a collection of encapsulated processing components or modules, each dedicated to performing a particular cognitive function. On this view, selective impairments of cognitive tasks following brain damage, as evidenced by double dissociations, are naturally interpreted in terms of the loss of particular processing components. By contrast, the current investigation examines in detail a double dissociation between concrete and abstract work reading after damage to a connectionist network that pronounces words via meaning and yet has no separable components (Plaut & Shallice, 1993). The functional specialization in the network that gives rise to the double dissociation is not transparently related to the network's structure, as modular theories assume. Furthermore, a consideration of the distribution of effects across quantitatively equivalent individual lesions in the network raises specific concerns about the interpretation of single-case studies. The findings underscore the necessity of relating neuropsychological data to cognitive theories in the context of specific computational assumptions about how the cognitive system operates normally and after damage.

Brain Damage, Chronic↗
PubMed2006

Attractor dynamics in a modular network model of neocortex.

Starting from the hypothesis that the mammalian neocortex to a first approximation functions as an associative memory of the attractor network type, we formulate a quantitative computational model of neocortical layers 2/3. The model employs biophysically detailed multi-compartmental model neurons with conductance based synapses and includes pyramidal cells and two types of inhibitory interneurons, i.e., regular spiking non-pyramidal cells and basket cells. The simulated network has a minicolumnar as well as a hypercolumnar modular structure and we propose that minicolumns rather than single cells are the basic computational units in neocortex. The minicolumns are represented in full scale and synaptic input to the different types of model neurons is carefully matched to reproduce experimentally measured values and to allow a quantitative reproduction of single cell recordings. Several key phenomena seen experimentally in vitro and in vivo appear as emergent features of this model. It exhibits a robust and fast attractor dynamics with pattern completion and pattern rivalry and it suggests an explanation for the so-called attentional blink phenomenon. During assembly dynamics, the model faithfully reproduces several features of local UP states, as they have been experimentally observed in vitro, as well as oscillatory behavior similar to that observed in the neocortex.

Action Potentials↗
PubMedDate not supplied

Effects of modular course training on mobility in older adults aged 79-90 years.

PURPOSE: To determine the effectiveness of an intervention programme utilizing modules specifically designed to challenge mobility in older adults. METHOD: Twelve older adults aged 79-90 years (84.3+/-3.2; mean+/-SD) living in a retirement community participated in a 10-week (3 sessions per week, 50 minutes per session) training programme. Performance on a modular course, comprised of nine stations representing common environmental conditions, provided information about dynamic balance and mobility before and after the intervention programme. Stations consisted of walking across carpet and foam pathways, walking up and down ramps and stairs, walking through a slalom course of eight plastic cones, and stepping over foam props. Performance on the mobility course was videotaped to determine the time to complete each station. The training intervention consisted of performing sections of the mobility course and standing on foam pads with the eyes open or closed. RESULTS: Using the Bonferroni-adjusted level of significance for multiple comparisons (p+/-0.005), paired sample t-tests indicated significant improvement for total time to complete the course (pre=100.9+/-40.5 s, post=79.6+/-40.3 s) and for all individual stations except stepping over props. CONCLUSIONS: These results indicate that an intervention programme utilizing functionally-oriented modules can improve mobility in older adults.

Accidental Falls↗
PubMed2002

Phenomenological perspectives on the folding of beta/alpha-barrel domains through the modular formation and assembly of smaller structural elements.

The beta/alpha-barrel motif was once considered to be a single protein domain. In recent years, however, it has been shown to consist of smaller substructures displaying the ability to fold autonomously. Here we review the current status of experimental findings concerning the motif's folding behavior in the light of what is currently known about (a) the relative rates of formation of helices and sheets in proteins, in general, and (b) the peculiarities of topology and architecture of the motif, in particular, to develop a detailed phenomenological understanding of how beta/alpha-barrels might form through the modular folding and assembly of substructures.

Models, Molecular↗
PubMed1996

The sea urchin sperm receptor for egg jelly is a modular protein with extensive homology to the human polycystic kidney disease protein, PKD1.

During fertilization, the sea urchin sperm acrosome reaction (AR), an ion channel-regulated event, is triggered by glycoproteins in egg jelly (EJ). A 210-kD sperm membrane glycoprotein is the receptor for EJ (REJ). This conclusion is based on the following data: purified REJ binds species specifically to EJ dotted onto nitrocellulose, an mAb to REJ induces the sperm AR, antibody induction is blocked by purified REJ, and purified REJ absorbs the AR-inducing activity of EJ. Overlapping fragments of REJ cDNA were cloned (total length, 5,596 bp). The sequence was confirmed by microsequencing six peptides of mature REJ and by Western blotting with antibody to a synthetic peptide designed from the sequence. Complete deglycosylation of REJ followed by Western blotting yielded a size estimate in agreement with that of the mature amino acid sequence. REJ is modular in design; it contains one EGF module and two C-type lectin carbohydrate-recognition modules. Most importantly, it contains a novel module, herein named the REJ module (700 residues), which shares extensive homology with the human polycystic kidney disease protein (PKD1). Mutations in PKD1 cause autosomal dominant polycystic kidney disease, one of the most frequent genetic disease of humans. The lesion in cellular physiology resulting from mutations in the PKD1 protein remains unknown. The homology between REJ modules of the sea urchin REJ and human PKD1 suggests that PKD1 could be involved in ionic regulation.

Amino Acid Sequence↗
PubMed2004

Selection in modular organisms: is intraclonal variation in macroalgae evolutionarily important?

Theoretical and practical difficulties occur when defining the units of selection in modular organisms that grow by iteration of repeated parts (modules). Modules may become physically autonomous through fragmentation and may vary because of genetic variation arising in somatic cell lineages. Since cells destined for gamete production are not sequestered in early development, heritable variation and selection among asexual progeny are possible. We used the branching red macroalgae Delisea pulchra and Asparagopsis armata to test whether modules fulfill three fundamental criteria for units of selection: that they replicate, that they display heritable variation, and that selective agents distinguish among the variants. We detected significant phenotypic variation among modules for fitness-related traits (growth, secondary metabolite concentrations, and rates of tissue loss to herbivory) in each species and significant heritability estimates for secondary metabolite production and tissue loss to herbivory in D. pulchra. Variation in growth rate among A. armata modules was largely phenotypic with small but important estimates of genetic variation. Our results indicate that selection may indeed act on phenotypic variation among modules within individuals and that this process may effect evolutionary change within asexual lineages given sufficient genetic variation in the traits examined.

Animals↗
PubMed1991

A modular approach to multichannel magnetometry.

A 19-channel SQUID system for biomagnetic measurements has been developed. This system differs from standard instruments in its modular approach. Various gradiometers can be coupled to the SQUIDs, the cryogenic system allows the exchange of single channels and the electronics is based on a cassette system. Problems with thermal insulation, vibrations of the gradiometers and tilted gradiometer geometries are discussed and solutions are presented.

Equipment Design↗
PubMed2001

Mk3.5: a modular, multi-frequency successor to the Mk3a EIS/EIT system.

This paper describes the Sheffield Mk3.5 EIT/EIS system which measures both the real and imaginary part of impedance at 30 frequencies between 2 kHz and 1.6 MHz. The system uses eight electrodes with an adjacent drive/receive electrode data acquisition protocol. The system is modular, containing eight identical data acquisition boards, which contain DSPs to generate the drive frequencies and to perform the FFT used for demodulation. The current drive is in three sequentially applied packets, where each packet contains ten summed sine waves. The data acquisition system is interfaced to a host PC through an optically isolated high speed serial link (RS485) running at 2 Mbaud (2 Mbits s(-1)). Measurements on a saline filled tank show that the average signal to noise performance of the system is 40 dB measured across all frequencies and that this figure is independent of frequency of measurement. These results suggest that the current system is 10 dB better in absolute terms than the previous Sheffield (Mk3a) system.

Electric Impedance↗
PubMedDate not supplied

Tissue factory: conceptual design of a modular system for the in vitro generation of functional tissues.

Tissue factory is a modular system designed to generate artificial tissues under optimal perfusion culture conditions. The microenvironment within the culture containers can be fine-tuned to meet the physiological needs of individual tissues, so that the generation of differentiated three-dimensional tissue constructs becomes possible. An optimal physiological environment is created by modulating a liquid phase as well as an artificial interstitium surrounding the growing construct. An innovative construction principle allows production of tissue culture containers, gas exchangers, and gas expanders at minimal material expenditure. Therefore it will be possible for the first time to produce sterile one-way perfusion culture modules for the generation of artificial tissues. The modules can be used separately as well as in a combined module. The system is designed to provide a possible platform for the standardized production of artificial tissues for future applications in biomedicine.

Cell Culture Techniques↗