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At least 235 records · Page 13Linked to original sources
PubMed1992

HTLV-I Tax is a zinc-binding protein: role of zinc in Tax structure and function.

We have examined the functional significance of the cysteine- and histidine-rich region (amino acids 22-53) of HTLV-I Tax. A modeling of this region suggests two possible overlapping zinc-finger-like motifs. Using a zinc blotting technique, we show that Tax binds zinc. An N-terminal deletion in Tax that removed this zinc-finger region abolished the ability to bind zinc. Site-directed mutagenesis was used to generate 10 separate mutations so as to discriminate between the two alternative zinc-binding structures. Each Tax mutant was studied for its ability to trans-activate the HTLV-I LTR. Five of the ten mutations inactivated trans-activation. Our results support that one of the two putative zinc fingers is an integral element of Tax structure.

Amino Acid Sequence↗
PubMed1994

The mechanism of transposition of Tc3 in C. elegans.

The Tc3 transposon of C. elegans belongs to a family of inverted repeat DNA transposons, found in many different phyla. We studied the mechanism of Tc3 transposition by expression of Tc3 transposase from a heat-shock promoter in transgenic nematodes. Transposition is accompanied by the appearance of linear extrachromosomal Tc3 DNA. Analysis of the ends of this presumed transposition intermediate shows that the transposon is excised incompletely: the 5' ends of the transposon lack two nucleotides. The 3' ends coincide with the last nucleotide of the integrated element and carry 3' hydroxyls. The nucleotides that are not coexcised with the transposon remain at the donor site and result in a characteristic footprint. A model is derived for the mechanism of Tc3 jumping that probably applies to the entire family of Tc1/mariner transposable elements.

Animals↗
PubMed1987

Intracellular recordings from interneurons and motoneurons in intact flying locusts.

A preparation is described in which it is possible to record intracellularly from identified motoneurons and interneurons during flight in intact tethered locusts. Intracellular recordings could be obtained from either the large somata of the motoneurons or from the neuropil processes of interneurons and motoneurons in either the meso- or metathoracic ganglion. Intracellular recordings from motoneuron somata were sufficiently stable to allow surgical manipulations, e.g. deafferentation, of the nervous system without the loss of penetration. Recordings from neuropil processes required stabilizing the ganglion by sandwiching it between two supports. The preparation is suitable for the cellular analysis of many aspects of motor patterning in the flight system of the locust. So far we have used it to make a direct comparison between the patterns of synaptic activity in intact and deafferented animals. This comparison shows that sensory feedback from wing proprioceptors strongly influences the activity in elevator motoneurons and flight interneurons. From these and other observations we conclude that proprioceptive feedback is essential for generating important features of the intact motor pattern and that wing receptors are integral elements of the intact flight pattern generator.

Animals↗
PubMed1988

The expression of the Escherichia coli uvrA gene in human cells.

Cells cultured from xeroderma pigmentosum (XP) patients are defective in excision repair of damaged DNA specifically at the incision step. In Escherichia coli this step is mediated by the UvrA, UvrB and UvrC gene products. Our goal is to express each of these genes in XP cells, singly or in combination, and to determine the most suitable conditions for generating faithful E. coli Uvr protein copies in functional concentrations and properly localized for the eventual repair of damaged chromosomal DNA or DNA which is introduced exogenously. The E. coli gpt gene in pSV2gpt is used as a selection marker for uvr gene transfection into XP cells. The uvr genes were cloned into composite pBR322, SV40 and gpt vectors in which each E. coli gene is flanked by individual SV40 regulatory elements. SV40-transformed XP-A cells were transfected with pSV2uvrASV2gpt, gpt+ colonies were selected, and cell lines established. Several lines were examined in detail. Cell lines 714 and 1511 contain uvrA together with flanking SV40 regulatory elements integrated intact in genomic DNA and express UvrA protein as well as a 95,000-dalton UvrA-related protein. The expression of uvrA was found to be 50-100-fold lower than the expression of gpt. Attempts were made to assay the mammalian UvrA protein for functionality, but endogenous activities interfered with assays for each of the UvrA protein's three activities. The peptide maps derived from partial proteolysis of the "mammalian" UvrA protein are identical to the E. coli UvrA protein. The sub-cellular location of UvrA protein in uvrA+ XP cells was investigated by fractionation of cell extracts in which an indirect immunofluorescence method revealed its location as being largely extra-nuclear. Two uvrA+ cell lines were examined for their UV-resistant phenotype and not unexpectedly were found not to be reverted to a state of repair proficiency.

Bacterial Proteins↗
PubMed1990

Cutaneous horn of the penis: its association with squamous cell carcinoma and HPV-16 infection.

Cutaneous horns of the penis are rare. Including this case, only 19 cases have been reported in the English-language literature. In 37% of the reported cases a malignant tumor was found beneath the cutaneous horn. Our case is remarkable because a stage I squamous cell carcinoma developed on the shaft of the penis of a neonatally circumcised man. Human genital carcinoma resulting from a multifactorial process in which "promoting" papillomavirus is an integral element is being increasingly reported. We review the relationship of circumcision to genital human papillomavirus infection and their synergism in the development of squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed1984

Malay midwives and witches.

This paper attempts to analyse professional rivalry and dissonance amongst traditional Malay midwives (bidan kampung) in the Northwest areas of Peninsular Malaysia. It elucidates how techniques of symbolic and ritual communication are carefully monitored by these female specialists, to develop regular clientele and professional credibility over time. However, since an integral element of Malay midwifery is protection from and mastery over mystical forces in nature and evil spirits harboured by witches, a midwife is also an exorcist with skills rather similar to the Malay bomoh (traditional medical practitioner, usually male) except that her range of knowledge of witchcraft is limited to diagnostic and curative rituals of spirit-possession, in infants and children, young unmarried women and pregnant mothers. Within a restricted population area, professional rivalries and competition amongst midwives regularly surface in oblique attacks of witchcraft accusations where the accused strives to maintain her credibility while her accuser gradually wins over her clientele. Significantly, codes of professionalism in traditional Malay midwifery are not only determined by skill and experience, but also religiousness (faith in Islam), benevolence, virtue, diligence and a sense of equality and fair-play in the practice of the trade. These qualities are seemingly lacking in witches who are conceived to be anti-Islamic, uncompromising, manevolent and destructive. Thus, government midwives who threaten the popularity of traditional midwives by being particularly active in their work or supervising and controlling midwives in an authoritarian way, are also labelled as witches. Generally, while midwifery and witchcraft reflect two forms of knowledge that are structurally opposed, in ideology and morality, they exist within the same sphere of ritual and symbolic communication where the practitioners aided by their clients, shift from one state of dissonance to another in an attempt to regulate behaviour.

Humans↗
PubMed1989

The block to transcription elongation at the SV40 attenuation site is decreased in vitro by oligomers complementary to segments of the attenuator RNA.

We have previously reported that a mechanism resembling attenuation in prokaryotes regulates simian virus 40 (SV40) late gene expression. We have suggested that modulation of the attenuator RNA secondary structure is an integral element regulating the elongation block at the attenuation site [Hay et al., Cell 29 (1982) 183-193]. In the present study, oligodeoxyribonucleotides (oligos), 13-19 nucleotides long, were used to probe the involvement of the attenuator RNA secondary structure in the control of elongation block at the SV40 attenuation site. These oligos are complementary to segments of the attenuator RNA suggested to play a role in the regulation of attenuation. The oligos were added to an in vitro transcription reaction containing SV40 transcription complexes, and their effect on transcription through the attenuation site was measured. As predicted, the three oligos caused specific decreases in the elongation block at the SV40 attenuation site. These results provide direct evidence for the involvement of RNA secondary structure in the attenuation mechanism in SV40.

Animals↗
PubMed2005

Molecular imprinted polymer sensors: implications for therapeutics.

A biosensor is a sensor that uses biological selectivity to limit its perception to particular key molecules and can be defined as an analytical device possessing a biological or biologically derived sensing element integrated with or associated closely with a physicochemical transducer. In the future it is likely that a number of key developments in therapeutic monitoring and intelligent drug delivery will rely on real-time feedback information in order to deliver an appropriate response. However due to issues of integration and the fragility and unreliability of the bio-molecule, biosensors are currently unable to fulfil this role. Molecular imprinted polymers are viable alternatives to both antibodies and enzymes and this review considers the current position of molecular imprinted polymer sensing.

Biosensing Techniques↗
PubMed2006

Pathways that suppress programmed DNA breaks from progressing to chromosomal breaks and translocations.

Guarding the genome against internal and external assaults requires the coordinated interaction of multiple cellular networks to sense, respond to, and repair breaks in chromosomal DNA. Both external factors such as ionizing radiation or internal events like oxidative damage can cause DNA double stranded breaks (DSBs). DSBs are also part of the normal lymphocyte developmental program where they are an integral element of the mechanisms that generate a diverse immune repertoire in the context of V(D)J and immunoglobulin heavy chain (IgH) class switch recombination (CSR). DSBs initiate a cascade of cellular events that direct cells to pause and properly repair potentially lethal chromosomal breaks. Errors in the repair of both general and lymphocyte-specific DSBs can lead to oncogenic chromosomal translocations . Here, we review recent advances in understanding factors and protein complexes involved in the response to DNA DSBs with a focus on the B lymphocyte specific process of CSR.

Animals↗
PubMed2004

Regulators of nonsulfur purple phototrophic bacteria and the interactive control of CO2 assimilation, nitrogen fixation, hydrogen metabolism and energy generation.

For the metabolically diverse nonsulfur purple phototrophic bacteria, maintaining redox homeostasis requires balancing the activities of energy supplying and energy-utilizing pathways, often in the face of drastic changes in environmental conditions. These organisms, members of the class Alphaproteobacteria, primarily use CO2 as an electron sink to achieve redox homeostasis. After noting the consequences of inactivating the capacity for CO2 reduction through the Calvin-Benson-Bassham (CBB) pathway, it was shown that the molecular control of many additional important biological processes catalyzed by nonsulfur purple bacteria is linked to expression of the CBB genes. Several regulator proteins are involved, with the two component Reg/Prr regulatory system playing a major role in maintaining redox poise in these organisms. Reg/Prr was shown to be a global regulator involved in the coordinate control of a number of metabolic processes including CO2 assimilation, nitrogen fixation, hydrogen metabolism and energy-generation pathways. Accumulating evidence suggests that the Reg/Prr system senses the oxidation/reduction state of the cell by monitoring a signal associated with electron transport. The response regulator RegA/PrrA activates or represses gene expression through direct interaction with target gene promoters where it often works in concert with other regulators that can be either global or specific. For the key CO2 reduction pathway, which clearly triggers whether other redox balancing mechanisms are employed, the ability to activate or inactivate the specific regulator CbbR is of paramount importance. From these studies, it is apparent that a detailed understanding of how diverse regulatory elements integrate and control metabolism will eventually be achieved.

Alphaproteobacteria↗
PubMed2006

Extended DLVO interactions between spherical particles and rough surfaces.

An "extended DLVO" approach that includes Lifshitz-van der Waals, Lewis acid-base, and electrostatic double layer interactions is used to describe interaction energies between spherical particles and rough surfaces. Favorable, unfavorable, and intermediate deposition conditions are simulated using surface properties representing common aquatic colloids and polymeric membranes. The surface element integration (SEI) technique and Derjaguin's integration method are employed to calculate interaction energy. Numerical simulations using SEI demonstrate that nanometer scale surface roughness features can produce a distribution of interaction energy profiles. Local interaction energies are statistically analyzed to define representative interaction energy profiles-minimum, average, and maximum-for various combinations of simulated particles and surfaces. In all cases, the magnitude of the average interaction energy profile is reduced, but the reduction of energy depends on particle size, asperity size, and density of asperities. In some cases, a surface that is on average unfavorable for deposition (repulsive) may possess locally favorable (attractive) sites solely due to nanoscale surface roughness. A weighted average of the analytical sphere-sphere and sphere-plate expressions of Derjaguin reasonably approximates the average interaction energy profiles predicted by the SEI model, where the weighting factor is based on the fraction of interactions involving asperities.

Journal Article↗
PubMed2004

Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4.1.

Aquaporin-4 (AQP4) is the predominant water channel in the neuropil of the central nervous system. It is expressed primarily in astrocytes, but also occurs in ependymocytes and endothelial cells. A striking feature of AQP4 expression is its polarized distribution in brain astrocytes and retinal Muller cells. Thus, immunogold analyses have revealed an enrichment of AQP4 in endfeet membranes in contact with brain microvessels or subarachnoidal space and a low but significant concentration in non-endfeet membranes, including those astrocyte membranes that ensheath glutamate synapses. The subcellular compartmentation of AQP4 mimics that of the potassium channel Kir4.1, which is implicated in spatial buffering of K(+). We propose that AQP4 works in concert with Kir4.1 and the electrogenic bicarbonate transporter NBC and that water flux through AQP4 contributes to the activity dependent volume changes of the extracellular space. Such volume changes are important as they affect the extracellular solute concentrations and electrical fields, and hence neuronal excitability. We conclude that AQP4-mediated water flux represents an integral element of brain volume and ion homeostasis.

Animals↗
PubMed2006

Making the cut: protease-mediated regulation of angiogenesis.

Angiogenesis is an integral element of normal physiologic development as well as of wound healing and a variety of pathologic conditions. Since the earliest studies of the cellular processes required for the formation of new capillaries from preexisting vessels, proteolysis has been recognized as one of the earliest and most sustained activities involved in these events. Several proteases including matrix metalloproteases (MMPs), and the closely related ADAM (a disintegrin and metalloprotease domain) and ADAMTS (a disintegrin and metalloprotease domain with thrombospondin motifs) families, as well as cysteine and serine proteases, have been implicated in this regulation. The current review addresses the contribution of these proteases in the positive and negative regulation of angiogenesis as mediated by degradation of the endothelial basement membrane and extracellular matrix proteins, release of angiogenic factors, processing of cytokines, growth factors and growth factor receptors, and the production of endogenous inhibitors.

Animals↗
PubMed1999

Risk stratification for cardiac valve replacement. National Cardiac Surgery Database. Database Committee of The Society of Thoracic Surgeons.

BACKGROUND: The Society of Thoracic Surgeons National Database Committee is committed to risk stratification and assessment as integral elements in the practice of cardiac operations. The National Cardiac Surgery Database was created to analyze data from subscribing institutions across the country. We analyzed the database for valve replacement procedures with and without coronary artery bypass grafting to determine trends in risk stratification. METHODS: The database contains complete records of 86,580 patients who had valve replacement procedures at the participating institutions between 1986 and 1995, inclusive. The 1995 harvest of data was conducted in late 1996 and available for evaluation in 1997. These records were used to conduct an in-depth analysis of risk factors associated with valve replacement and to provide prediction of operative death by using regression analysis. Regression models were made for six subgroups. RESULTS: Adverse patient risk factors, including diabetes, hypertension and reoperation, but not ventricular function, increased over time. There were trends with regard to increasing age of the various population subsets. The types of prostheses used remained similar over time, with more mechanical prostheses than bioprostheses used for both aortic and mitral valve replacement. There was a trend toward increased use of bioprostheses in aortic replacements and decreased use in mitral replacements between 1991 and 1995 than between 1986 and 1990. The mortality rate was determined by patient subset for primary operation and reoperation and by urgency status. The modeling showed that the predicted and observed mortality correlated for all age groups and within patient subsets. CONCLUSIONS: Risk modeling is a valuable tool for predicting the probability of operative death in any individual patient. This large, multiinstitutional database is capable of determining modern operative risk and should provide standards for acceptable care. The study illustrates the importance of risk stratification for early death both for the patient and the surgeon.

Adult↗
PubMed2001

Direct measurements of multiple adhesive alignments and unbinding trajectories between cadherin extracellular domains.

Direct measurements of the interactions between antiparallel, oriented monolayers of the complete extracellular region of C-cadherin demonstrate that, rather than binding in a single unique orientation, the cadherins adhere in three distinct alignments. The strongest adhesion is observed when the opposing extracellular fragments are completely interdigitated. A second adhesive alignment forms when the interdigitated proteins separate by 70 +/- 10 A. A third complex forms at a bilayer separation commensurate with the approximate overlap of cadherin extracellular domains 1 and 2 (CEC1-2). The locations of the energy minima are independent of both the surface density of bound cadherin and the stiffness of the force transducer. Using surface element integration, we show that two flat surfaces that interact through an oscillatory potential will exhibit discrete minima at the same locations in the force profile measured between hemicylinders covered with identical materials. The measured interaction profiles, therefore, reflect the relative separations at which the antiparallel proteins adhere, and are unaffected by the curvature of the underlying substrate. The successive formation and rupture of multiple protein contacts during detachment can explain the observed sluggish unbinding of cadherin monolayers. Velocity-distance profiles, obtained by quantitative video analysis of the unbinding trajectory, exhibit three velocity regimes, the transitions between which coincide with the positions of the adhesive minima. These findings suggest that cadherins undergo multiple stage unbinding, which may function to impede adhesive failure under force.

Animals↗
PubMed1997

Co-localization of vasoactive intestinal polypeptide, gamma-aminobutyric acid and choline acetyltransferase in neocortical interneurons of the adult rat.

Interneurons immunoreactive for vasoactive intestinal polypeptide (VIP) are integral elements of columnar organization patterns in the rat cerebral cortex. By application of the sensitive mirror technique, the co-localization of VIP with the classical inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the acetylcholine-synthesizing enzyme, choline acetyltransferase (ChAT), was investigated in neocortical neurons. Furthermore, the frequency of co-localization of ChAT with GABA was determined. In a sample of 118 VIP-immunoreactive neurons, mostly from the primary somatosensory cortex, it was demonstrated that virtually all of them reveal immunoreactivity for GABA and, therefore, are to be GABAergic. Moreover, 34% of mostly bipolar, VIP-positive neurons contained ChAT and are, thus, supposedly cholinergic as well. Co-localization of VIP and ChAT varied according to cortical laminae. Finally, 88% of a total of 60 ChAT-immunoreactive neurons were also immunostained for GABA. It is concluded that almost all VIP-immunoreactive neurons and most of the cholinergic neurons in rat neocortex represent partly overlapping subpopulations of inhibitory interneurons utilizing GABA.

Animals↗
PubMed2005

[Randomized clinical trials (CONSORT)].

It has been repeatedly shown that the information supplied in publications of clinical trials is frequently insufficient or inaccurate and that some methodologic problems are associated with exaggerated estimates of the effect of healthcare interventions. To improve the quality of reports of clinical trials, a group of scientists and editors developed the CONSORT statement (Consolidated Standards of Reporting Trials), a 22-item checklist (plus flow diagram), that can be used by authors, editors, reviewers, and readers. After publication in 1996, CONSORT was adopted by several journals and editorial groups. In 1999, a second version was drawn up, which was published in 2001. This article presents the Spanish translation of the two elements integrating the revised CONSORT, the flow diagram and the 22-item checklist, and provides a short comment on each of them. Previous publications of the CONSORT statement and other useful resources such as examples of what are considered good communications may be obtained from the CONSORT web site (http://www.consort-statement.org).

Authorship↗
PubMed1998

Cancer prevention: past, present, future.

There are many examples of different types of cancers that have been prevented by appropriate measures in the past. Most of them were related to occupational, iatrogenic or accidental factors, often as the outcome of heavy exposure of humans to specific carcinogenic agents. Cancer is a disease of DNA, and is generally associated with multiple genetic alterations, these being produced in the typical case by exposure to various carcinogens, each of which exists at minute concentrations. Thus, the impact of carcinogenic factors, xenobiotics and autobiotics, is due to their actions in concert. However, a single mutation yielding genomic instability exerts a disproportionately large influence by resulting in a large number of secondary mutational events. Epigenetic changes can also not be disregarded especially from the view point of prevention of neoplasia. The occurrence of multiple primary cancers among survivors of initial primaries, and the presence of hereditary groups with a high risk of cancer development provide a strong stimulus for establishment of effective approach for cancer prevention, which should be, in principle, multi-faceted. Therefore, a holistic approach is essential with improvement in life style including choosing a balanced diet and avoidance of cigarette smoking and other sources of carcinogens, as integral elements.

Anticarcinogenic Agents↗