PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Pathway informed transformer”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

Tracking microbial populations effective in reducing exposure.

Microbial ecology provides the link between basic biochemical and molecular studies on toxicity reduction by microbial metabolism and environmental studies that determine exposure. This link provides the ability to determine which microorganisms are responsible for the actual transformations in nature, thereby establishing how predictive the laboratory pathway, kinetic, regulatory, and enzyme mechanistic information is for nature. This information can be important to the rate of toxicant removal, the type and concentration of intermediate product(s), and the identification of conditions that limit effective toxicant removal. Nucleic acid-based methods now provide the main means to track important biodegrading populations. Examples of these methods are given that illustrate tracking a biodegrading microbe injected into an aquifer, following community succession in a toluene-degrading fluidized bed reactor, aiding the isolation from nature of novel biodegrading organisms, and rapidly characterizing the extent of microbial diversity in an aquifer stimulated to co-metabolize trichloroethene.

Biodegradation, Environmental↗

Ornithine decarboxylase overexpression in mouse 10T1/2 fibroblasts: cellular transformation and invasion.

BACKGROUND: Ornithine decarboxylase (ODC) plays a pivotal role in the synthesis of polyamines, a group of chemical compounds that are essential for cell growth. Recent reports have shown that ODC overexpression may be involved in malignant transformation of immortalized NIH 3T3 cells. We have demonstrated that ODC-overproducing mouse breast cancer cells are more invasive in vitro than control cells. However, little information is available concerning the relationship between ODC overexpression, tumor invasion, and metastasis and the signal transduction pathways involved in ODC-induced transformation and invasion. PURPOSE: Our purpose was twofold: 1) to determine whether ODC overexpression is directly involved in tumor cell invasion and 2) to determine whether ODC overexpression induces mitogen-activated protein (MAP) kinase activities that are associated with cell growth and transformation. METHODS: We transfected C3H clone 8 mouse 10T1/2 fibroblasts with an expression vector that carries a complementary DNA encoding rat ODC. Neomycin-resistant cells that overproduced ODC (4-6.5 times the control levels) were isolated. The transformed phenotype of these cells was determined by assessing colony formation and anchorage-independent growth in soft agar. The invasiveness of the cells was studied by means of an invasion assay that used Matrigel-coated filters in Boyden chambers. The MAP kinase activity of the cells was assayed by an in-gel kinase assay, using myelin basic protein as the substrate. RESULTS: Overexpression of ODC induced not only cell transformation and anchorage-independent growth in soft agar but also invasiveness through a Matrigel-coated filter. The ODC-overproducing transfectants showed enhanced MAP kinase activity that paralleled the magnitude of cell invasiveness. CONCLUSIONS: ODC plays a pivotal role not only in cell transformation but also in cancer cell invasion. ODC overexpression enhanced MAP kinase activity. IMPLICATIONS: Our results demonstrate a connection between the polyamine/ODC and the MAP kinase signal transduction pathways and suggest that MAP kinase may play a pivotal role in ODC-induced cell transformation and invasion.

Animals↗

Clinically relevant physiology of the vestibulo-ocular reflex.

This review attempts to explain those aspects of the physiology of the vestibulo-ocular reflex (VOR) which could be of future clinical value. The literature cited has been selected for its didactic worth to readers with limited time, preferring concise reviews to detailed reports wherever possible. Physiological data provide the background for the following possible improvements in clinical diagnosis: 1) In gaze analysis, coordination of the VOR with other motor patterns can be analyzed. 2) Precision of vestibular tests can be improved by selecting stimuli within the range of natural movements.3) Resolution of the caloric test can be imporved when the change of temperature at the semicircular canal mimics endolymph pressure changes during natural movements. 4) A direct test of the three neuron VOR pathways is possible, but not practicable. 5) Integration of the input signal (transformation from head acceleration to eye position information) can be directly tested. 6) Plasticity (the adaptation to visual requirements) of the VOR can be examined. 7) It is possible to quantify vestibular damage and detect the side of lesion in one test analyzing gain and binocular symmetry of the vertical VOR.

Cerebellum↗

Long- and short-patch gene conversions in Streptococcus pneumoniae transformation.

In pneumococcal transformation some point mutations are integrated by an excision-repair pathway which switches the heteroduplex DNA into homoduplex. This transfer of information is a gene conversion. We have reviewed some of the properties of this system especially those relating to heteroduplex specificity and given evidence that this extends over several kilobases of DNA. We then describe a new process of conversion in pneumococcal transformation which occurs over a very short distance (5 to 27 base-pairs) and is triggered by a single site mutation resulting from the transversion 5'-ATTCAT...to 5'...ATTAAT... Only one of the two heteroduplexes 5'...A...3'/3'...G...5', is converted.

Base Sequence↗

Signal transformations required for the generation of saccadic eye movements.

Chronic unit recording experiments conducted over the past two decades have identified many functional classes of neurons with saccade-related activity that reside in a host of brainstem nuclei. Older models of the saccadic system were based upon the properties of only a few of these functional types of neurons. They described the putative flow of signals through the brainstem circuitry and specified some, but not all, of the signal transformations to be performed. How the necessary computations were performed by neurons was not always explicit. Recent experiments investigating the neural control of saccadic eye movements and modifications of the original models are designed to fill in the details of the broad sketch of saccadic circuitry originally available. This review suggests one strategy for proceeding with this effort. Saccadic command signals observed in the SC require transformation to interface with the burst generators and motoneuron pools innervating the extraocular muscles. Specifying the signal transformations required for this interface should facilitate the design of experiments directed toward an understanding of the functional properties of cells located in nuclei intervening between the SC and the pulse/step circuitry, subsets of neurons that often have no role in models of the saccadic system. In this review, we hypothesize that neurons residing in various tectorecipient brainstem nuclei participate in one or more of the required signal transformations. The pathway from SC to cMRF and PPRF may be involved in the extraction of information about the amplitude and/or velocity of the horizontal component of oblique saccades. The pathway from SC to NRTP and cerebellar vermis may act selectively to generate signals compensating for the presaccadic orbital position. Finally, the activity of LLBNs and MLBs discharging maximally before oblique saccades may form the basis of computations required to match component velocity with overall saccade direction and amplitude. Although the data supporting these speculations are meager at present, such conjectures do form the basis of working hypotheses that can be tested experimentally. We also considered the implications of kinematic constraints, especially Donders' and Listing's laws, for future investigations. Tweed & Vilis (1987, 1990) proposed models specifically designed to handle these constraints. In their models, eye position is represented on four oculomotor channels: three coding the vector components of eye position, and one carrying a signal inversely related to gaze eccentricity and torsion. Yet, other evidence suggest that simpler computations may suffice for the implementation of laws that are only approximately obeyed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Comparative cytomorphometric and cytospectrophotometric investigations of gastric lesions.

Comparative cytomorphometric and cytospectrophotometric investigations have been carried out on Hematoxylin-Eosin and Feulgen stained paraffin sections from 150 patients with normal gastric mucosa, chronic atrophic and hypertrophic gastritis, benign and malignantly transformed stomach ulcers and adenomatous polyps and adenocarcinoma of the stomach. The changes in the small and large nucleus (cell) diameters; nucleus, cell and cytoplasma area (volume) and nucleus/cell and nucleus/cytoplasma ratio for area and volume as well as the nuclear DNA content values have been presented in the pathway from normal stomach mucosa to gastric cancer. The presented results give us more information about the dynamics of malignant cell transformation.

Adenocarcinoma↗

Lipid mediators of angiogenesis and the signalling pathways they initiate.

Investigations carried out over the past 3 years have implicated a key role for sphingosine 1-phosphate (SPP) in angiogenesis and blood vessel maturation. SPP is capable of inducing almost every aspect of angiogenesis and vessel maturation in vitro, including endothelial cell chemotaxis, survival, proliferation, capillary morphogenesis and adherence antigen deployment, as well as stabilizing developing endothelial cell monolayers and recruitment of smooth muscle cells to maturing vessels. Acting in conjunction with protein angiogenic factors, SPP induces prolific vascular development in many established models of angiogenesis in vivo. Thus, SPP is a unique, potent and multifaceted angiogenic agent. While SPP induces angiogenic effects by ligating members of the endothelial differentiation gene (EDG) G-protein-coupled family of receptors, recent studies suggest that endogenously produced SPP may also account for the ability of tyrosine kinase receptors to induce cell migration. Thus, SPP provides a clear link between tyrosine kinase and G-protein-coupled receptor agonists involved in the angiogenic response. However, the mechanisms by which SPP exerts its effects on vascular cells remain unclear, conflicting and controversial. Precise definition of the signalling pathways by which SPP induces specific aspects of the angiogenic response promises to lead to new and effective therapeutic approaches to regulate angiogenesis at sites of tissue damage, neoplastic transformation and inflammation. This review will trace the discovery of SPP as a novel angiogenic factor as it outlines present information on the signalling pathways by which SPP induces its effects on cells of the developing vascular bed.

Animals↗

Gravity perception requires statoliths settled on specific plasma membrane areas in characean rhizoids and protonemata.

The noninvasive infrared laser micromanipulation technique (optical tweezers, optical trapping) and centrifugation were used to study susception and perception, the early events in the gravitropic pathway of tip-growing characean rhizoids and protonemata. Reorientation of the growth direction in both cell types was only initiated when at least 2-3 statoliths settled on specific areas of the plasma membrane. This statolith-sensitive plasma membrane area is confined to the statolith region (10-35 microns behind the tip) in positively gravitropic rhizoids, whereas in negatively gravitropic protonemata, this area is limited to the apical plasma membrane (0-10 microns). Statolith sedimentation towards the sensitive plasma membrane areas is mediated by the concerted action of actin and gravity. The process of sedimentation, the pure physical movement, of statoliths is not sufficient to initiate graviresponses in both cell types. It is concluded that specific statolith-sensitive plasma membrane areas play a crucial role in the signal transduction pathway of gravitropism. These areas may represent the primary sites for gravity perception and may transform the information derived from the gravity-induced statolith sedimentation into physiological signals which trigger the molecular mechanisms of the opposite graviresponses in characean rhizoids and protonemata.

Actin Cytoskeleton↗

Visuomotor control: where does vision end and action begin?

A new understanding of how visual information is transformed into motor acts has emerged from recent studies of the organization of the visuomotor pathways in the primate brain. This work suggests that it may no longer be useful, or even correct, to categorize different brain areas as sensory or motor.

Animals↗

Signaling circuitries in development: insights from the retinal determination gene network.

Context-specific integration of information received from the Notch, Transforming growth factor beta, Wingless/Wnt, Hedgehog and Epidermal growth factor receptor signaling pathways sets the stage for deployment of the retinal determination gene network (RDGN), a group of transcription factors that collectively directs the formation of the eye and other tissues. Recent investigations have revealed how these transcription factors are regulated by their interactions with each other and with effectors of the above signaling pathways. Further study of the RDGN may provide insights into how common cues can generate context-specific responses, a key aspect of developmental regulation that remains poorly understood.

Animals↗

Carcinogenesis and the hypothesis of phylogenetic reversion.

Chemoprevention must target early molecular events involved in malignant transformation. The sequence of events leading from a normally functioning interphase cell to an uncontrolled tumor cell is only partially understood, impeding systematic design of chemopreventive agents. The respective roles of mutagenic and epigenetic mechanisms have not been definitively established. Also, traditional models do not appear to incorporate cellular response to events leading to carcinogenesis. A perspective on system response offered by complexity science elucidates the roles of feedback and control in maintaining functional stability during carcinogenesis. Carcinogenesis is seen as a process of epigenetic redifferentiation resulting in a cell behaving like an archetypal karyocyte free of growth restraints (phylogenetic reversion). Genes that evolved during the development of multicellular organisms, restraining uncontrolled growth and regulating intercell communication may be systematically silenced during carcinogenesis. The formation of heterochromatin, which results in epigenetic silencing by hypermethylation in CpG-dense islands, finds expression in the nuclear chromatin pattern. Karyometry is an integrating biomarker of chromatin pattern information that accommodates the possibility of multiple, differently ordered pathways and provides exquisite sensitivity, allowing detection of very early transformation events. Its use can monitor the impact of chemopreventive agents on the earliest events in progression to cancer.

Animals↗

Normal and transforming functions of RUNX1: a perspective.

Converging studies from many investigators indicate that RUNX1 has a critical role in the correct maintenance of essential cellular functions during embryonic development and after birth. The discovery that this gene is also frequently mutated in human leukemia has increased the interest in the role that RUNX1 plays in both normal and transforming pathways. Here, we provide an overview of the many roles of RUNX1 in hematopoietic self-renewal and differentiation and summarize the information that is currently available on the many mechanisms of RUNX1 deregulation in human leukemia.

Animals↗

Linear and nonlinear pathways of spectral information transmission in the cochlear nucleus.

At the level of the cochlear nucleus (CN), the auditory pathway divides into several parallel circuits, each of which provides a different representation of the acoustic signal. Here, the representation of the power spectrum of an acoustic signal is analyzed for two CN principal cells-chopper neurons of the ventral CN and type IV neurons of the dorsal CN. The analysis is based on a weighting function model that relates the discharge rate of a neuron to first- and second-order transformations of the power spectrum. In chopper neurons, the transformation of spectral level into rate is a linear (i.e., first-order) or nearly linear function. This transformation is a predominantly excitatory process involving multiple frequency components, centered in a narrow frequency range about best frequency, that usually are processed independently of each other. In contrast, type IV neurons encode spectral information linearly only near threshold. At higher stimulus levels, these neurons are strongly inhibited by spectral notches, a behavior that cannot be explained by level transformations of first- or second-order. Type IV weighting functions reveal complex excitatory and inhibitory interactions that involve frequency components spanning a wider range than that seen in choppers. These findings suggest that chopper and type IV neurons form parallel pathways of spectral information transmission that are governed by two different mechanisms. Although choppers use a predominantly linear mechanism to transmit tonotopic representations of spectra, type IV neurons use highly nonlinear processes to signal the presence of wide-band spectral features.

Acoustic Stimulation↗

The complete genome sequence of the lactic acid bacterium Lactococcus lactis ssp. lactis IL1403.

Lactococcus lactis is a nonpathogenic AT-rich gram-positive bacterium closely related to the genus Streptococcus and is the most commonly used cheese starter. It is also the best-characterized lactic acid bacterium. We sequenced the genome of the laboratory strain IL1403, using a novel two-step strategy that comprises diagnostic sequencing of the entire genome and a shotgun polishing step. The genome contains 2,365,589 base pairs and encodes 2310 proteins, including 293 protein-coding genes belonging to six prophages and 43 insertion sequence (IS) elements. Nonrandom distribution of IS elements indicates that the chromosome of the sequenced strain may be a product of recent recombination between two closely related genomes. A complete set of late competence genes is present, indicating the ability of L. lactis to undergo DNA transformation. Genomic sequence revealed new possibilities for fermentation pathways and for aerobic respiration. It also indicated a horizontal transfer of genetic information from Lactococcus to gram-negative enteric bacteria of Salmonella-Escherichia group.

Amino Acids↗

Plasticity of brainstem mechanisms of cough.

The cough reflex is a brainstem reflex, consisting of specific sensory afferent nerves which trigger the reflex, by transmitting the sensory input over vagal or laryngeal nerves to a brainstem circuitry which processes and ultimately transforms the sensory input into a complex motor output to generate cough. The first synaptic target for the primary cough-related sensory input is the second-order neurons in the nucleus tractus solitarius (NTS). This position in the reflex pathway and intricate local circuits within the nucleus make it a strategic site where the sensory information can be modified. Plasticity at this synapse will change the nature of the output--exaggerating it, suppressing it or transforming it into some other complex pattern. This review integrates evidence implicating the NTS in exaggerated cough with proof of the concept that NTS neurons undergo plasticity to contribute to an exaggeration of cough.

Afferent Pathways↗

The Drosophila TGF-alpha-like protein Gurken: expression and cellular localization during Drosophila oogenesis.

The establishment of anterior-posterior and dorsal-ventral polarity of the Drosophila egg and embryo depends on the function of the genes gurken, cornichon and Egfr (Drosophila epidermal growth factor receptor homolog). These genes encode components of a signal transduction pathway that transmits information between the germline cells and the somatic follicle cells of the ovary. gurken encodes a transforming growth factor-alpha-like protein and is a putative germline ligand of the Egfr present on the follicle cells. In mid-oogenesis the gurken transcript becomes spatially localized to the future dorsal-anterior cortex of the oocyte. To analyze the distribution pattern of Gurken protein we prepared antibodies against Gurken. We describe here the distribution pattern of the Gurken protein in wild-type ovaries and in ovaries from a number of dorsal-ventral patterning mutants. By immunoblotting we detect one major form of the Gurken protein, which likely corresponds to the unprocessed protein.

Animals↗

Biotransformation of N-nitrosodimethylamine by Pseudomonas mendocina KR1.

N-Nitrosodimethylamine (NDMA) is a potent carcinogen and an emerging contaminant in groundwater and drinking water. The metabolism of NDMA in mammalian cells has been widely studied, but little information is available concerning the microbial transformation of this compound. The objective of this study was to elucidate the pathway(s) of NDMA biotransformation by Pseudomonas mendocina KR1, a strain that possesses toluene-4-monooxygenase (T4MO). P. mendocina KR1 was observed to initially oxidize NDMA to N-nitrodimethylamine (NTDMA), a novel metabolite. The use of 18O2 and H(2)18O revealed that the oxygen added to NDMA to produce NTDMA was derived from atmospheric O2. Experiments performed with a pseudomonad expressing cloned T4MO confirmed that T4MO catalyzes this initial reaction. The NTDMA produced by P. mendocina KR1 did not accumulate, but rather it was metabolized further to produce N-nitromethylamine (88 to 94% recovery) and a trace amount of formaldehyde (HCHO). Small quantities of methanol (CH3OH) were also detected when the strain was incubated with NDMA but not during incubation with either NTDMA or HCHO. The formation of methanol is hypothesized to occur via a second, minor pathway mediated by an initial alpha-hydroxylation of the nitrosamine. Strain KR1 did not grow on NDMA or mineralize significant quantities of the compound to carbon dioxide, suggesting that the degradation process is cometabolic.

Biotransformation↗

Molecular genetics of acute lymphoblastic leukemia.

From its beginnings two decades ago with the analysis of chromosomal translocation breakpoints, research into the molecular pathogenesis of acute lymphoblastic leukemia (ALL) has now progressed to the large-scale resequencing of candidate oncogenes and tumor suppressor genes in the genomes of ALL cases blocked at various developmental stages within the B- and T-cell lineages. In this review, we summarize the findings of these investigations and highlight how this information is being integrated into multistep mutagenesis cascades that impact specific signal transduction pathways and synergistically lead to leukemic transformation. Because of these advances, fueled by improved technology for mutational analysis and the development of small-molecule drugs and monoclonal antibodies, the future is bright for a new generation of targeted therapies. Best illustrated by the successful introduction of imatinib mesylate, these new treatments will interfere with disordered molecular pathways specific for the leukemic cells, and thus should exhibit much less toxicity and fewer long-term adverse effects than currently available therapeutic modalities.

Child↗