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PubMed1980

A theory of modular evolution for bacteriophages.

The modular theory of virus evolution has clear experimental support among the temperate bacteriophages of the enteric bacteria. However, there is also similar genetic and DNA heteroduplex evidence for such evolution among other families of bacteriophages: the virulent bacteriophages of the enterics comprise several families: the T-even group, the T3-T7 group (which has many members among different species of bacteria, including bacteria as widely divergent as E. coli and Caulobacter crescentus. It nicely explains the diffusion of very similar homologous bacteriophages into hosts whose own DNAs have diverged very greatly from each other in nucleotide sequence. It also accounts for the rigorous maintenance of regulatory schemes while units of function (including regions coding for proteins) diverge more rapidly. It should also be noted that the considerations that make modular evolution seem advantageous for bacteriophages apply equally well to viruses of higher organisms. Furthermore, the kinds of heteroduplex similarity observed among animal viruses are reminiscent of what is found for bacteriophages. Viruses found in widely divergent hosts show much greater similarity than would be expected; quite possibly animal viruses also evolve as a population of interchangeable modules.

Bacteriophage lambda↗

PubMed1998

Plasposons: modular self-cloning minitransposon derivatives for rapid genetic analysis of gram-negative bacterial genomes.

A series of modular mini-transposon derivatives which permit the rapid cloning and mapping of the DNA flanking the minitransposon's site of insertion has been developed. The basic plasposon, named TnMod, consists of the Tn5 inverted repeats, a conditional origin of replication, rare restriction endonuclease multiple cloning sites, and exchangeable antibiotic resistance cassettes. The broad host range and low target DNA sequence specificity of the Tn5 transposase, in combination with the flexibility afforded by the modular arrangement of TnMod, result in a versatile tool for the mapping of insertional mutations and the rapid recovery of clones from gram-negative bacteria.

DNA Transposable Elements↗

PubMed1993

Efficient transcriptional activation of many simple modular promoters by simian virus 40 large T antigen.

Simian virus 40 (SV40) large T antigen is a multifunctional protein which plays central roles during both lytic and transforming infections by SV40. It is a potent transcriptional activator and increases expression from the SV40 late promoter and from several cellular promoters. To understand better the transcriptional activation activity of large T antigen, we examined its ability to transactivate a set of simple modular promoters containing one of four upstream activation sequences coupled with one of three different TATA box sequences originally constructed and studied by Taylor and Kingston (Mol. Cell. Biol. 10:165-175, 1990). Large T antigen activated transcription from all of these simple promoters. The identity of the TATA box was a more important determinant of the final level of gene expression than was the identity of the upstream activating sequence element. We also determined the ability of a set of mutant SV40 large T antigens to activate a subset of these promoters. Several mutant SV40 large T antigens which had reduced ability to activate the complex SV40 late and Rous sarcoma virus long terminal repeat promoters showed reduced transcriptional activation activity on all of the modular promoters tested. We used a set of promoter derivatives of the human U6 small nuclear RNA promoter containing different TATA boxes and found that wild-type large T antigen could activate transcription from all of them, although to widely different levels of expression.

Animals↗

PubMed1982

Construction of a modular dihydrofolate reductase cDNA gene: analysis of signals utilized for efficient expression.

Dihydrofolate reductase (DHFR) modular genes have been constructed with segments containing the adenovirus major late promoter, a 3' splice site from a variable region immunoglobulin gene, a DHFR cDNA, and portions of the simian virus 40 (SV40) genome. DNA-mediated transfer of these genes transformed Chinese hamster ovary DHFR- cells to the DHFR+ phenotype. Transformants contained one to several copies of the transfected DNA integrated into the host genome. Clones subjected to growth in increasing concentrations of methotrexate eventually gave rise to lines containing several hundred copies of the transforming DNA. Analysis of the DHFR mRNA produced in amplified lines indicated the following. (i) All clones utilize the adenovirus major late promoter for transcription initiation. (ii) A hybrid intron formed by the 5' splice site of the adenovirus major late leader and a 3' splice site from a variable-region immunoglobulin gene is properly excised. (iii) The mRNA is not efficiently polyadenylated at sequences in the 3' end of the DHFR cDNA but rather uses polyadenylation signals downstream from the DHFR cDNA. Three independent clones produce a DHFR mRNA containing SV40 or pBR322 and SV40 sequences, and the RNA is polyadenylated at the SV40 late polyadenylation site. Another clone has recombined into cellular DNA and apparently uses a cellular sequence for polyadenylation. Introduction of a segment containing the SV40 early polyadenylation signal into the 3' end of the DHFR cDNA gene generated a recombinant capable of transforming cells to the DHFR+ phenotype with at least a 10-fold increase in efficiency, demonstrating the necessity for an efficient polyadenylation signal. Attachment of a DNA segment containing the transcription enhancer (72-base pair repeat) of SV40 further increased the biological activity of the modular DHFR gene 50- to 100-fold.

Adenoviridae↗

PubMed1985

TU elements: a heterogeneous family of modularly structured eucaryotic transposons.

We describe here a family of foldback transposons found in the genome of the higher eucaryote, the sea urchin Strongylocentrotus purpuratus. Two major classes of TU elements have been identified by analysis of genomic DNA and TU element clones. One class consists of largely similar elements with long terminal inverted repeats (IVRs) containing outer and inner domains and sharing a common middle segment that can undergo deletions. Some of these elements contain insertions. The second class is highly heterogeneous, with many different middle segments nonhomologous to those of the first-class and variable-sized inverted repeats that contain only an outer domain. The middle and insertion segments of both classes carry sequences that also are found unassociated from the inverted repeats at many other genomic locations. We conclude that the TU elements are modular structures composed of inverted repeats plus other sequence domains that are themselves members of different families of dispersed repetitive sequences. Such modular elements may have a role in the dispersion and rearrangement of genomic DNA segments.

Animals↗

PubMed1998

Spinal cord modular organization and rhythm generation: an NMDA iontophoretic study in the frog.

Previous work using electrical microstimulation has suggested the existence of modules subserving limb posture in the spinal cord. In this study, the question of modular organization was reinvestigated with the more selective method of chemical microstimulation. N-methyl--aspartate (NMDA) iontophoresis was applied to 229 sites of the lumbar spinal cord gray while monitoring the isometric force output of the ipsilateral hindlimb at the ankle. A force response was elicited from 69 sites. At 18 of these sites, tonic forces were generated and rhythmic forces at 44. In the case of tonic forces, their directions clustered along four orientations: lateral extension, rostral flexion, adduction, and caudal extension. For the entire set of forces (tonic and rhythmic), the same clusters of orientations were found with the addition of a cluster directed as a flexion toward the body. This distribution of force orientations was quite comparable to that obtained with electrical stimulation at the same sites. The map of tonic responses revealed a topographic organization; each type of force orientation was elicited from sites that grouped together in zones at distinct rostrocaudal and depth locations. In the case of rhythmic sequences of force orientations, some were distinctly more common, whereas others were rarely elicited by NMDA. Mapping of the most common rhythms showed that each was elicited from two or three regions of the cord. These regions were close in location to the tonic regions that produced those forces that represented components specific to that rhythm. There was an additional caudal region from which the different rhythms also could be elicited. Taken together, these results support the concept of a modular organization of the motor system in the frog's spinal cord and delineate the topography of these modules. They also suggest that these modules are used by the circuitry underlying rhythmic pattern generation by the spinal cord.

Animals↗

PubMed1988

A modular arrangement of neuronal processes in human cortex: disruption with aging and in Alzheimer's disease.

Studies were undertaken to assess whether or not neuron-specific immunostaining of the human brain can reveal unique cytoarchitectural features that may be affected by healthy aging and Alzheimer's disease (AD). Human prefrontal cortex (PFC) and anterior cingulate cortex (ACC) were stained with an antibody raised against the neurofilament protein 200,000 molecular weight subunit (NFP-200) using an avidin-biotin immunolocalization procedure. Immunostaining of cortex was neuron-specific and highlighted axons in particular. This staining has revealed an orderly arrangement of horizontal and vertical axon bundles which form latticelike compartments or modules throughout most of the matrix of the two cortical areas studied. The ACC shows this pattern to be intact in individuals through the ninth decade, while the PFC there was blurring of the modularity beyond the fifth decade. Irrespective of the age-related blurring of the latticelike arrangement of axons in PFC, neurologically normal elderly individuals nevertheless showed a highly organized appearance to the cortical matrix. By contrast, patients with AD showed a marked disruption of the modular arrangement of fibers in PFC, but not ACC. Differences between PFC fibers in controls and AD patients were also demonstrated with an axon-specific monoclonal antibody that reacted with phosphorylated epitopes of the NFP-200. The chaotic appearance of fiber staining in PFC seen in patients with AD was noted to be present in one subject who died in an early stage of the disease. The possible significance of this previously unknown aspect of cortical cytoarchitecture for normal cognitive functioning in humans is discussed.

Adolescent↗

PubMed1995

Design of a non-constrained, non-cemented, modular, metacarpophalangeal prosthesis.

A non-constrained, non-cemented, modular prosthesis for replacement of the metacarpophalangeal joints of the fingers has been developed. The prosthesis is of a surface design which is modular in construction and is implanted into the bones with a press fit. The prosthesis is designed to be implanted into patients with traumatic injuries, post-traumatic osteoarthritis and into patients with rheumatoid arthritis at an early stage in the disease where the muscles and ligaments that surround the joint are still functional and can provide joint stability.

Arthritis, Rheumatoid↗

PubMedDate not supplied

The Modular Propad and the Softform mattress.

Constant low-pressure supports such as soft mattresses can feel comfortable because they conform well to the shape of the body. When such mattresses are provided with a highly convoluted surface made up of contiguous foam pillars, their efficacy is improved. The Modular Propad is a highly convoluted, but shallow, foam mattress. It is used as an overlay for an ordinary mattress and seems to be superior to earlier forms of convoluted foam overlay. The Softform is a new mattress which has replaceable sections. The outermost sections of the Softform are convoluted foam sheets similar to the Modular Propad. This article discusses the advantages and disadvantages of these products and some potential problems with their covers. It also suggests that the use of a pressure sore risk assessment tool can facilitate the allocation of patients to these special supports.

Beds↗

PubMed1991

Corrosion of modular hip prostheses.

Nine uncemented hip prostheses of modular design were revised because of late infection (2 cases), femoral stem loosening or fracture (2), loosening of threaded cups (3) and protrusion of bipolar cups (2). At surgery we found tissue discoloration and macroscopic corrosion in four of the nine prostheses, located at the head-neck junction. Histological examination in most cases showed extensive necrosis associated with metal particles, indicating metal toxicity. Metallographic examination of the prosthetic heads revealed structural imperfections and inhomogeneity of the metal. We suggest that the crevice between the head and neck is a potential site of corrosion in modular designs.

Adolescent↗

PubMed2025

Modularization of the type II secretion gene cluster from Xanthomonas euvesicatoria facilitates the identification of a structurally conserved XpsCLM assembly platform complex.

Many bacterial pathogens depend on a type II secretion (T2S) system to secrete virulence factors from the periplasm into the extracellular milieu. T2S systems consist of an outer membrane secretin channel, a periplasmic pseudopilus and an inner membrane-associated assembly platform including a cytoplasmic ATPase. The components of T2S systems are often conserved in different bacterial species, however, the architecture of the assembly platform is largely unknown. Here, we analysed predicted assembly platform components of the Xps-T2S system from the plant-pathogenic bacterium Xanthomonas euvesicatoria. To facilitate these studies, we generated a modular xps-T2S gene cluster by Golden Gate assembly of single promoter and gene fragments. The modular design allowed the efficient deletion and replacement of T2S genes and the insertion of reporter fusions. Mutant approaches as well as interaction and crosslinking studies showed that the predicted assembly platform components XpsC, XpsL and XpsM form a trimeric complex which is essential for T2S and associates with the cytoplasmic ATPase XpsE and the secretin XpsD. Structural modeling revealed a similar trimeric architecture of XpsCLM homologs from Pseudomonas, Vibrio and Klebsiella species, despite overall low amino acid sequence similarities. In X. euvesicatoria, crosslinking and fluorescence microscopy studies showed that the formation of the XpsCLM complex is independent of the secretin and vice versa, suggesting that the assembly of the T2S system is a dynamic process which involves the association of preformed subcomplexes.

Xanthomonas↗

PubMed1997

Modular organization of Pax/homeodomain proteins in transcriptional regulation.

Specificity in transcriptional regulation lies in a large part in the specificity of DNA binding by transcription factors. One group of transcription factors which are of great interest for studying transcriptional specificity is the Pax/Homeodomain (Pax/HD) proteins which contain two conserved DNA binding domains, a paired domain (PD) and a Paired-class homeodomain (HD). The Pax/HD proteins can bind to at least three types of specific DNA sequences: the PD binding sites, the dimeric HD binding sites and a composite HD and PD binding site. We propose that Pax/HD proteins regulate different subsets of their target genes through modular binding to one of these three specific sequences. We show that, in a tissue culture system, a member of the Pax/HD family, Paired, is able to activate transcription after binding through either its PD or its HD. The transactivation mediated by one domain does not require DNA binding of the other domain. Furthermore, binding sites specific for the PD of Paired are sufficient to mediate embryonic expression of a reporter gene in a paired-like pattern. The expression of the reporter gene is dependent on wild type paired function and, in a prd mutant background, it can be rescued by an exogenous paired gene encoding a protein whose HD is not able to bind to DNA. Finally, we show that the Paired protein uses differently its C-terminal activation domain when transactivation is mediated through its PD or its HD. These results and recent evidence from other Pax/HD proteins strongly suggest that this class of proteins is able to achieve specific and modular transcriptional regulation through its multiple DNA binding domains.

Animals↗

PubMed1997

Horizontal projections of area 17 in Cebus monkeys: metric features, and modular and laminar distribution.

Metric features and modular and laminar distributions of intrinsic projections of area 17 were studied in Cebus apella. Anterogradely and retrogradely labeled cell appendages were obtained using both saturated pellets and iontophoretic injections of biocytin into the operculum. Laminar and modular distributions of the labeled processes were analyzed using Nissl counterstaining, and/or cytochrome oxidase and/or NADPH-diaphorase histochemistry. We distinguished three labeled cell types: pyramidal, star pyramidal and stellate cells located in supragranular cortical layers (principally in layers IIIa, IIIb alpha, IIIb beta and IIIc). Three distinct axon terminal morphologies were found, i.e., Ia, Ib and II located in granular and supragranular layers. Both complete and partial segregation of group I axon terminals relative to the limits of the blobs of V1 were found. The results are compatible with recent evidence of incomplete segregation of visual information flow in V1 of Old and New World primates.

Animals↗

PubMed1994

Migration of corrosion products from modular hip prostheses. Particle microanalysis and histopathological findings.

Migration of solid corrosion products from the modular head-neck junction of fifteen total hip replacements to the periprosthetic tissues was studied. The devices and tissues were recovered at the time of a revision procedure or at autopsy after a mean of sixty-four months (range, eight to ninety-seven months). The prostheses had a cobalt-chromium-alloy head coupled with a cobalt-chromium-alloy or a titanium-alloy stem. The solid corrosion product was identified by electron microprobe analysis and Fourier transform infrared microprobe spectroscopy as a chromium orthophosphate hydrate-rich material. The product was present at the junction of the modular head and neck and as particles within the periprosthetic tissues as early as eight months postoperatively. In several hips, it was also present on the polyethylene bearing surface. The particles in the tissues ranged in size from less than one to 500 micrometers. They were present within histiocytes or were surrounded by foreign-body giant cells in the pseudocapsule of the hip joint; in the membranes of the femoral bone-implant interface; and at sites of femoral endosteal erosions, with and without loosening of the femoral component.

Adult↗

PubMed1997

The press-fit condylar modular total knee system. Four-to-six-year results with a posterior-cruciate-substituting design.

One hundred and eighteen patients who had had 150 consecutive primary total knee replacements (sixteen bilateral procedures) between February 1988 and February 1990, with insertion of the press-fit condylar modular total knee system with cement, were enrolled in a prospective study. Ninety-six patients (125 knees) were followed for an adequate interval (mean, 4.8 years; range, 3.8 to 6.2 years). Thirteen patients (fifteen knees) died, and nine patients (ten knees) were lost to follow-up. The mean age of the patients at the time of the index arthroplasty was seventy years (range, twenty-nine to eighty-five years). The patients were evaluated clinically and radiographically, according to the scoring system of the Knee Society, and the results on a self-administered questionnaire were used to evaluate pain, function, satisfaction, and patellofemoral symptoms. A Kaplan-Meier survivorship analysis was performed with a revision operation as the end point. The mean functional and clinical scores, according to the system of the Knee Society, were 78 and 93 points, respectively, at the most recent follow-up examination. The result was excellent for 103 knees, good for thirteen, fair for three, and poor for six. Three revision operations were necessary: two because of infection and one because of instability. The over-all rate of patellofemoral symptoms was 8 per cent (ten knees). Three knees had tibiofemoral instability; subsequent modification of the design of the tibial cam decreased the prevalence of this problem. Non-progressive radiolucent lines were present at the cement-bone interface in 39 per cent (thirty-nine) of the ninety-nine knees that had complete radiographic follow-up. No prosthesis had loosened by the time of the most recent follow-up examination. The rate of survival of the implant was 97 per cent at six years, and the standard error of the mean was 1.6 per cent. In the present series, total knee arthroplasties with the press-fit condylar modular knee system resulted in excellent relief of pain, an excellent range of motion, and restoration of function. They were also associated with a low prevalence of patellofemoral problems.

Adult↗

PubMed1983

Isometric muscle strength and endurance after knee arthroplasty with the modular knee in patients with osteoarthrosis and rheumatoid arthritis.

Maximum isometric muscle strength and endurance were used in an investigation of knee extension and knee flexion in patients with rheumatoid arthritis (RA) and osteoarthrosis (OA) with such severe changes of the joint that arthroplasty with the Modular prosthesis was performed. The measurements were done preoperatively and 3, 12, 24 and 36 months postoperatively. Muscle strength preoperatively was very weak compared with that of a group of healthy persons. The muscle strength 3 months postoperatively remained unchanged, which could mean a very slight trauma from the operation, very good pain relief and efficient physiotherapy. During the first 2 years the maximum isometric muscle strength was significantly increased both in patients with RA and in those with OA. Thereafter there was no increase in the RA patients, whereas in women with OA there was an improvement up to 3 years postoperatively. The improvement in the flexion strength was greater than that of the extension strength, thus indicating the importance of postoperative training of extension strength. Isometric muscle strength measurements show that there is an equalization between the non-diseased knee and the one operated with the Modular knee.

Aged↗

PubMed1997

A modular endoprosthetic system for tumor and non-tumor reconstruction: preliminary experience.

Though originally designed to facilitate the management of primary malignant bone tumors, the indications for the Howmedica Oncology modular endoprostheses have expanded to include the reconstruction of metastatic lesions, failed internal fixation of difficult trauma problems, and failed conventional and custom tumor endoprostheses. Between July 1989 and August 1992, 24 patients underwent 25 procedures, either proximal humeral replacement (7), proximal femoral replacement (5), distal femoral replacement (9), or total femoral replacement (4). Diagnoses included primary bone tumor (6), metastases (5), and failed previous orthopedic intervention (14). Two early and four late complications in five patients were all treated successfully with surgical or nonoperative treatment. Preliminary functional results indicate very satisfactory results. Modular endoprostheses appear to be effective in the treatment of a wide range of diagnoses, not limited to the reconstruction following primary malignant bone tumor resections.

Adolescent↗

PubMedDate not supplied

The canine cemented modular total hip prosthesis.

Total hip replacement (THR) is well established as a treatment modality for dogs with noninfectious, nonneoplastic, disabling conditions of the coxofemoral joint. Since the mid 1970s, a fixed-head prosthesis has been used in this procedure. A modular prosthesis, which is based on many of the technical advances found in human prostheses, now is available for use in veterinary medicine. The prosthesis, surgical instrumentation, surgical technique, and clinical results have been evaluated in a prospective study conducted at The Ohio State University's College of Veterinary Medicine. The modular prosthesis provides results equal to or better than the fixed-head prosthesis.

Animals↗