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Results for “Pathway informed transformer”

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PubMed2006

PageMan: an interactive ontology tool to generate, display, and annotate overview graphs for profiling experiments.

BACKGROUND: Microarray technology has become a widely accepted and standardized tool in biology. The first microarray data analysis programs were developed to support pair-wise comparison. However, as microarray experiments have become more routine, large scale experiments have become more common, which investigate multiple time points or sets of mutants or transgenics. To extract biological information from such high-throughput expression data, it is necessary to develop efficient analytical platforms, which combine manually curated gene ontologies with efficient visualization and navigation tools. Currently, most tools focus on a few limited biological aspects, rather than offering a holistic, integrated analysis. RESULTS: Here we introduce PageMan, a multiplatform, user-friendly, and stand-alone software tool that annotates, investigates, and condenses high-throughput microarray data in the context of functional ontologies. It includes a GUI tool to transform different ontologies into a suitable format, enabling the user to compare and choose between different ontologies. It is equipped with several statistical modules for data analysis, including over-representation analysis and Wilcoxon statistical testing. Results are exported in a graphical format for direct use, or for further editing in graphics programs.PageMan provides a fast overview of single treatments, allows genome-level responses to be compared across several microarray experiments covering, for example, stress responses at multiple time points. This aids in searching for trait-specific changes in pathways using mutants or transgenics, analyzing development time-courses, and comparison between species. In a case study, we analyze the results of publicly available microarrays of multiple cold stress experiments using PageMan, and compare the results to a previously published meta-analysis.PageMan offers a complete user's guide, a web-based over-representation analysis as well as a tutorial, and is freely available at http://mapman.mpimp-golm.mpg.de/pageman/. CONCLUSION: PageMan allows multiple microarray experiments to be efficiently condensed into a single page graphical display. The flexible interface allows data to be quickly and easily visualized, facilitating comparisons within experiments and to published experiments, thus enabling researchers to gain a rapid overview of the biological responses in the experiments.

Database Management Systems↗

PubMed2005

Fibril modelling by sequence and structure conservation analysis combined with protein docking techniques: beta(2)-microglobulin amyloidosis.

Obtaining atomic resolution structural models of amyloid fibrils is currently impossible, yet crucial for our understanding of the amyloid mechanism. Different pathways in the transformation of a native globular domain to an amyloid fibril invariably involve domain destabilization. Hence, locating the unstable segments of a domain is important for understanding its amyloidogenic transformation and possibly control it. Since relative conservation is suggested to relate to local stability, we performed an extensive, sequence and structure conservation analysis of the beta(2)-microglobulin (beta(2)-m) domain. Our dataset include 51 high resolution structures belonging to the "C1 set domain" family and 132 clustered PSI-BLAST search results. Segments of the beta(2)-m domain corresponding to strands A (residues 12-18), D (45-55) and G (91-95) were found to be less conserved and stable, while the central strands B (residues 22-28), C (36-41), E (62-70) and F (78-83) were found conserved and stable. Our findings are supported by accumulating observations from various experimental methods, including urea denaturation, limited proteolysis, H/D exchange and structure determination by both NMR and X-ray crystallography. We used our conservation findings together with experimental literature information to suggest a structural model for the polymerized unit of beta(2)-m. Pairwise protein docking and subsequent monomer stacking in the same manner suggest a fibril model consistent with the cross-beta structure.

Amyloid↗

PubMed2026

The Role of Genetic Variation in Phenotypic Variability in Loeys-Dietz Syndrome.

BACKGROUND: Loeys-Dietz syndrome (LDS) is a heritable connective tissue disorder caused by pathogenic variants in genes of the transforming growth factor-β (TGF-β) signaling pathway. Although genotype-phenotype correlations have been suggested, comprehensive comparative data across LDS subtypes remain limited. Improved understanding of these correlations is essential to guide individualized surveillance and management strategies. METHODS: We conducted a retrospective cohort study of adults with genetically confirmed LDS evaluated between 2018 and 2024 across Mayo Clinic sites. Patients with pathogenic, likely pathogenic, or suspicious variants in TGFBR1, TGFBR2, or SMAD3 were included. Clinical characteristics, physical examination findings, cardiovascular and noncardiovascular manifestations, surgical interventions, and mortality were compared across genotypes. Categorical variables were analyzed using chi-square tests and continuous variables using parametric or nonparametric methods as appropriate. RESULTS: A total of 93 patients were included (29 TGFBR1, 33 TGFBR2, 31 SMAD3). Demographics and mortality did not differ significantly between groups. Patients with TGFBR1 and TGFBR2 demonstrated trends toward higher rates of ascending aortic aneurysm and aortic dissection compared with SMAD3 patients, though these differences were not statistically significant. Renal artery aneurysms were significantly more common in TGFBR1 patients (13.8%, p = 0.010). SMAD3 patients had significantly higher rates of mitral regurgitation (54.8%, p = 0.04), peripheral neuropathy (29.0%, p = 0.018), and trends toward increased atrial fibrillation and osteoarthritis. A novel association was identified between TGFBR1 variants and migraine, which was significantly more prevalent in this group (62.1%, p = 0.017). The rates of major cardiovascular surgical interventions were high and comparable across all genotypes. CONCLUSION: Distinct genotype-phenotype associations exist among LDS subtypes. TGFBR1 and TGFBR2 variants are associated with a greater burden of aggressive vascular disease, whereas SMAD3 variants are linked to mitral valve disease, peripheral neuropathy, and osteoarthritis. We also identified a novel association between TGFBR1 genotype and migraine. These findings reinforce the importance of comprehensive genetic testing to inform personalized surveillance and management strategies in LDS.

Humans↗

PubMed1990

Horizontal and vertical components of head movement are controlled by distinct neural circuits in the barn owl.

To generate behaviour, the brain must transform sensory information into signals that are appropriate to control movement. Sensory and motor coordinate frames are fundamentally different, however: sensory coordinates are based on the spatiotemporal patterns of activity arising from the various sense organs, whereas motor coordinates are based on the pulling directions of muscles or groups of muscles. Results from psychophysical experiments suggest that in the process of transforming sensory information into motor control signals, the brain encodes movements in abstract or extrinsic coordinate frames, that is ones not closely related to the geometry of the sensory apparatus or of the skeletomusculature. Here we show that an abstract code underlies movements of the head by the barn owl. Specifically, the data show that subsequent to the retinotopic code for space in the optic tectum yet before the motor neuron code for muscle tensions there exists a code for head movement in which upward, downward, leftward and rightward components of movement are controlled by four functionally distinct neural circuits. Such independent coding of orthogonal components of movement may be a common intermediate step in the transformation of sensation into behaviour.

Animals↗

PubMed2000

Use of green fluorescent protein (GFP) to study the invasion pathways of Edwardsiella tarda in in vivo and in vitro fish models.

Edwardsiella tarda is a fish pathogen that causes systemic infections in many food and ornamental fish. E. tarda PPD130/91 and PPD125/87 were selected as representatives of the virulent and avirulent groups, respectively, from eight fish isolates, and transformed with plasmids encoding either green fluorescent protein (pGFPuv) or blue fluorescent protein (pBFP2). Two host models were used to study the invasion pathway of E. tarda in vitro and in vivo. Epithelioma papillosum of carp (EPC) was used as the first model. Virulent and avirulent E. tarda strains were found to adhere to and invade EPC cells. Interactions between E. tarda and host cells examined under confocal microscopy and intracellular growth were followed at different time points. Bacterial internalization of PPD130/91 and PPD125/87 involved microfilaments and protein tyrosine kinase since cytochalasin D (an inhibitor of microfilament polymerization) and genistein (an inhibitor of protein tyrosine kinase) prevented internalization. Confocal studies revealed co-localization of polymerized actin with bacteria. Staurosporine, a protein kinase C inhibitor, accelerated internalization of PPD125/87, whereas PD098059, a mitogen-activated protein kinase (MAPK) kinase inhibitor prevented internalization of PPD130/91. In the second model, blue gourami were infected with E. tarda intramuscularly. Mortalities were observed in PPD130/91(pGFPuv)-infected fish with high bacterial numbers detectable in all organs. PPD125/87(pBFP2)-infected fish did not die and the bacterial population decreased over time. Mixed infections comprised of both PPD130/91(pGFPuv) and PPD125/87(pBFP2), where inoculum size was similar to the single infections, caused mortalities in fish. High bacterial populations were noted only in the fish body muscle. The PPD125/87(pBFP2) population in the fish decreased after 5 d. The number of PPD130/91(pGFPuv) also decreased in the fish organs, except for continued high growth in the body muscle. Histology revealed necrosis of the tissue (body muscle and liver) and fluorescent bacteria in fish that were infected with PPD130/91(pGFPuv) but not with PPD125/87(pBFP2). This study showed that fluorescent proteins are a useful tool for investigating bacterial host cell infection, and information elucidated here sheds new light on the interactions between E. tarda and its hosts.

Actins↗

PubMed2005

A study of archaeal enzymes involved in polar lipid synthesis linking amino acid sequence information, genomic contexts and lipid composition.

Cellular membrane lipids, of which phospholipids are the major constituents, form one of the characteristic features that distinguish Archaea from other organisms. In this study, we focused on the steps in archaeal phospholipid synthetic pathways that generate polar lipids such as archaetidylserine, archaetidylglycerol, and archaetidylinositol. Only archaetidylserine synthase (ASS), from Methanothermobacter thermautotrophicus, has been experimentally identified. Other enzymes have not been fully examined. Through database searching, we detected many archaeal hypothetical proteins that show sequence similarity to members of the CDP alcohol phosphatidyltransferase family, such as phosphatidylserine synthase (PSS), phosphatidylglycerol synthase (PGS) and phosphatidylinositol synthase (PIS) derived from Bacteria and Eukarya. The archaeal hypothetical proteins were classified into two groups, based on the sequence similarity. Members of the first group, including ASS from M. thermautotrophicus, were closely related to PSS. The rough agreement between PSS homologue distribution within Archaea and the experimentally identified distribution of archaetidylserine suggested that the hypothetical proteins are ASSs. We found that an open reading frame (ORF) tends to be adjacent to that of ASS in the genome, and that the order of the two ORFs is conserved. The sequence similarity of phosphatidylserine decarboxylase to the product of the ORF next to the ASS gene, together with the genomic context conservation, suggests that the ORF encodes archaetidylserine decarboxylase, which may transform archaetidylserine to archaetidylethanolamine. The second group of archaeal hypothetical proteins was related to PGS and PIS. The members of this group were subjected to molecular phylogenetic analysis, together with PGSs and PISs and it was found that they formed two distinct clusters in the molecular phylogenetic tree. The distribution of members of each cluster within Archaea roughly corresponded to the experimentally identified distribution of archaetidylglycerol or archaetidylinositol. The molecular phylogenetic tree patterns and the correspondence to the membrane compositions suggest that the two clusters in this group correspond to archaetidylglycerol synthases and archaetidylinositol synthases. No archaeal hypothetical protein with sequence similarity to known phosphatidylcholine synthases was detected in this study.

Archaea↗

PubMed1990

Intermolecular recombination between DNAs introduced into mouse L cells is mediated by a nonconservative pathway that leads to crossover products.

We describe experiments designed to measure the efficiency of intermolecular recombination between mutant herpesvirus thymidine kinase (tk) genes introduced into mouse L cells. Recombinants were scored as stable transformants containing a functional tk gene. The two recombination substrates used were ptkB8, a pBR322-based plasmid containing a mutant tk gene, with a BamHI linker in an SphI restriction site that is centrally located within the gene, and mp10tk delta 3' delta 5', an mp10 vector with a tk gene deleted at both the 3' and 5' ends. The only homology shared by the two DNAs is 885 base pairs within the tk gene. To determine whether the double-strand break repair model that has been used to explain recombination in yeast cells (J. W. Szostak, T. L. Orr-Weaver, R. J. Rothstein, and F. W. Stahl, Cell 33:25-35, 1983) can account for recombination during the introduction of these DNAs into mammalian cells, we transformed cells with BamHI-linearized ptkB8 and supercoiled mp10tk delta 3' delta 5' replicative-form DNA. These two DNAs should recombine efficiently according to that model and should generate gene conversion products. In this reaction, the supercoiled DNA acts as the donor of information to repair the cleaved tk gene. Our results indicated that the efficiency of this reaction was very low (less than 10 transformants were obtained per 0.1 microgram of each DNA used in the reaction per 10(6) cells). In contrast, if BamHI-cleaved ptkB8 DNA was cotransformed into cells along with a circular DNA molecule containing a tk gene deleted only at its 3' end or only at its 5' end (mp10tk delta 3' or mp10tk delta 5'), then the efficiency of recombination could be more than 4 orders of magnitude higher than it was with circular mp10tk delta 3' delta 5' DNA. Recombination frequencies were highest when the tk delta 3' or tk delta 5' DNA used was cleaved at the tk deletion junction. Southern analyses of DNA from TK+ transformants generated with BamHI-cleaved ptkB8 and BamHI-cleaved mp10tk delta 3' DNAs indicated that recombination was almost always associated with the reassortment of markers flanking the reconstructed tk DNA. Together, these results are more consistent with the nonconservative single-strand annealing model for recombination that we proposed several years ago (F.-L. Lin, K. Sperle, and N. Sternberg, Mol. Cell. Biol. 4:1020-1034, 1984) than they are with the double-strand break repair model.

Animals↗

PubMed2002

The pathogenesis of inflammatory bowel disease: translational implications for clinicians.

Research in the pathogenesis of inflammatory bowel disease (IBD) has dramatically broadened our understanding of these complex disorders. These clinical manifestations result from a dysregulated immune response in the presence of luminal bacteria. Recent identification of mutations in the NOD2 gene, a protein involved in the sensing of bacteria, offers genetic support for the model of perturbed host-microbial interactions in Crohn's disease. Several immunologic pathways have been identified that play a role in maintaining gut immune homeostasis. Abnormal expression of proinflammatory, deleterious cytokines such as tumor necrosis factor-a and interferon-g results in direct and indirect tissue damage. The search for specific causative microbial agents in IBD continues to be intense. This paper describes the advances in our understanding of IBD pathogenesis, with an emphasis on how this information is translated into patient care. The next stage of research will take advantage of such molecular biologic techniques to identify new pathogenetic mechanisms and targets for therapy tailored to individual patients.

Animals↗

PubMed2026

In situ product monitoring in heterogeneous reaction of gaseous trimethylamine on Fe2O3/Fe(NO3)3: Effect of environmental factor and particle property.

Gas-particle reactions represent an important atmospheric heterogeneous transformation process for organic amines (OAs). Environmental factors and particle properties may impact the gas-particle reaction products. Although the products from gas-particle reactions can be monitored by various in situ techniques, related data remain scarce. Here, the interfacial and gaseous products from the reaction of trimethylamine on Fe2O3/Fe(NO3)3 particles under light irradiation with mixed NO2, O2, SO2 and H2O were monitored using in-situ diffuse reflectance Fourier transform infrared spectroscopy and proton transfer reaction time-of-flight mass spectrometry. Dark reaction of gaseous trimethylamine on Fe2O3/Fe(NO3)3 generated two interfacial products types: N-containing ones (CH3NCH2, CH3NO2, (CH3)2NCHO, and CH3N(OH)CHO) and N-free ones (alcohols, aldehydes and acids), both accumulating with reaction progression. Light irradiation and O2 oxidation enhanced formation of these products, while NO2 promoted the production of CH3NO2 and (CH3)2NCHO. H2O and SO2 occupied the active sites of particles to inhibit the formation of all products. Compared to Fe(NO3)3, Fe2O3 showed absolute dominance in contribution to the formation of products. Considering the smaller particle size of Fe2O3 and excess Fe(NO3)3, the physical mixing of them reduced the generation of interfacial products. Furthermore, gaseous products of CH3OH, HCHO, CH3CHO, HCOOH and CH3COOH detection clarified the N-free interfacial products. The presence of Fe(NO3)3 inhibited the formation of HCOOH and favored the formation of CH3CHO in the gas phase. By combining product information with thermodynamic calculations, the heterogeneous reaction pathways of trimethylamine were tentatively proposed. These findings provide a guiding significance for the migration of OAs in real atmospheric environment.

Methylamines↗

PubMed2004

Expression of Fas ligand in retinoblastoma.

BACKGROUND: The importance of the Fas-Fas ligand (FasL) mechanism for the immune evasion by tumors provided a strong rationale for the examination of FasL expression in retinoblastoma. In an earlier publication, the authors reported that invasive retinoblastomas decreased Fas expression. Because to the authors' knowledge there is not much information regarding the effect of FasL expression on retinoblastoma, the authors studied the expression of FasL in retinoblastoma and correlated it with invasiveness. METHODS: Thirty-six archival retinoblastoma specimens were divided into 2 groups. Group A (n = 17) was comprised of specimens from tumors with no invasion and Group B (n = 19) was comprised of specimens from tumors with invasion of the choroid (focal, diffuse), optic nerve (laminar, postlaminar, surgical end), and orbit. Sections were immunostained with a monoclonal antibody to FasL and the immunoreactivity was assessed. RESULTS: In Group A, FasL was negative in 100% (17 of 17) of the tumor specimens. In Group B, FasL was expressed in 79% (15 of 19) of the tumor specimens (positive in 9 tumors and heterogeneous in 6 tumors). The difference in FasL expression between the two groups was significant (P < 0.001) CONCLUSIONS: Increased expression of FasL was observed in specimens taken from patients with aggressive tumors. Thus, Loss of Fas and gain of aberrant FasL expression were common features of malignant transformation. The data suggested that the Fas/FasL pathway is potentially immunosuppressive and may be involved in the escape of retinoblastoma cells from immune destruction.

Adolescent↗

PubMed1995

Speechreading supplemented by single-channel and multichannel tactile displays of voice fundamental frequency.

The benefits of two tactile codes of voice fundamental frequency (F0) were evaluated as supplements to the speechreading of sentences in two short-term training studies, each using 12 adults with normal hearing. In Experiment 1, a multichannel spatiotemporal display of F0, known as Portapitch, was used to stimulate the index finger. In an attempt to improve on past performance with this display, the coding scheme was modified to better cover the F0 range of the talker in the training materials. For Experiment 2, to engage kinesthetic/proprioceptive pathways, a novel single-channel positional display was built, in which F0 was coded as the vertical displacement of a small finger-rest. Input to both displays consisted of synthesized replicas of the F0 contours of the sentences, prepared and perfected off-line. Training with the two tactile F0 displays included auditory presentation of the synthesized F0 contours in conjunction with the tactile patterns on alternate trials. Speechreading enhancement by the two tactile F0 displays was compared to the enhancement provided when auditory F0 information was available in conjunction with the tactile patterns, by auditory presentation of a sinusoidal indication of the presence or absence of voicing, and by a single-channel tactile display of the speech waveform presented to the index finger. Despite the modified coding strategy, the multichannel Portapitch provided a mean tactile speechreading enhancement of 7 percentage points, which was no greater than that found in previous studies. The novel positional F0 display provided only a 4 percentage point enhancement. Neither F0 display was better than the simple single-channel tactile transform of the full speech waveform, which gave a 7 percentage point enhancement effect. Auditory speechreading enhancement effects were 17 percentage points with the voicing indicator and approximately 35 percentage points when the auditory F0 contour was provided in conjunction with the tactile displays. The findings are consistent with the hypothesis that subjects were not taking full advantage of the F0 variation information available in the outputs of the two experimental tactile displays.

Adult↗

PubMed1995

Vestibular integrators in the oculomotor system.

The interstitial nucleus of Cajal (INC) and the nucleus prepositus hypoglossi (nph) are key elements in the vertical and horizontal oculomotor neural integrators, respectively. In this article, we attempt to develop possible circuits for these vestibular integrators by synthesizing recent information on the properties and connections of neurons involved in the integration process. We also examine how the cerebellar flocculus could play a role in the vertical integrator and vestibulo-ocular reflex (VOR) as well as in the modulation and plasticity of the VOR. We suggest that the circuitry for the vertical integrator involves the cerebellar flocculus in addition to the already proposed circuits distributed between the INC and the vestibular nuclei. The horizontal vestibular integrator is also distributed and seems to be characterized by functional compartmentalization. Both integrators play a wider role than simply transforming velocity-coded signals into position commands and may be pivotal in the short- and long-term modulation of the various oculomotor subsystems.

Animals↗

PubMed1995

The proteasome from Thermoplasma acidophilum is neither a cysteine nor a serine protease.

The 20 S proteasome, found in eukaryotes and in the archaebacterium Thermoplasma acidophilum, forms the proteolytic core of the 26 S proteasome which is the central protease of the non-lysosomal protein degradation pathway. Inhibitor studies have indicated that the 20 S proteasome may be an unusual type of cysteine or serine protease and a recent study of the Thermoplasma beta subunit has indicated that it carries the proteolytic activity. We have attempted to obtain information on the nature of the active site by mutating the only cysteine, both histidines and two completely conserved aspartates in the archaebacterial complex as well as all serines of the beta subunit, without decreasing the catalytic activity of the enzyme to any significant extent. Indeed, mutation of the conserved aspartate in the beta subunit increased the activity of the proteasome threefold. We conclude that the proteasome is not a cysteine or serine protease.

Amino Acid Sequence↗

PubMed2007

Gene expression profiling of women with varying degrees of cervical intraepithelial neoplasia.

OBJECTIVE: A pilot study to determine genomic microarray differences in patients with normal cervical tissue and cervical intraepithelial neoplasia (CIN) 3. MATERIALS AND METHODS: After institutional review board approval, patients referred to the University of Alabama at Birmingham Colposcopy Clinic for a loop electrosurgical excisional procedure were identified. Tissue biopsies of both normal tissue and CIN 3 from fresh loop electrosurgical excisional procedure specimens were obtained and sent to pathology for histological confirmation. Procurement of these 2 types of tissue from the same patient controls for different types of human papillomavirus infection, smoking and nutritional status, age, immunocompetency, and other microenvironment factors (i.e., the patient serves as their own control). Standard RNA extraction techniques (Qiagen, Inc., Valencia, CA) were used to prepare the tissue specimens for microarray analysis with the Affymetrix GeneChip U133A expression array (Affymetrix, Inc., Santa Clara, CA). Paired samples were eligible for microarray analysis only when both normal tissue and CIN 3 were confirmed by pathology. The data were then subsequently subjected to a log-like transformation and analyzed with a t test. For this study, p<.001 was determined to be statistically significant. RESULTS: Twenty-one pairs of both normal and CIN tissues were obtained and underwent histological evaluation followed by RNA extraction. Within the normal group, 86% were confirmed as true normals and 14% as CIN. Within the CIN group, 28.5% were found to have CIN 2, 62% were found to have CIN 3, and 9.5% had no evidence of CIN. Mean RNA content of normal samples was 2.0 microg, whereas the mean RNA content of CIN samples was significantly higher at 7.4 microg (p=006). Ultimately, 5 pairs of normal and neoplastic tissues were subjected to microarray analysis. Using a cutoff of p<.001, 24 candidate genes were identified from more than 18,000 genes. In the CIN 3 group, 14 genes were overexpressed and 10 genes were underexpressed. Of the 14 overexpressed genes, 9 were noted to have identities listed in the National Center for Biotechnology Information public domain. Five (56%) of these 9 genes were directly related to immunity-related pathways, and 3 (33%) of the 9 genes were found to be involved in cell cycle function/control. One overexpressed gene was identified as p53. CONCLUSIONS: The presence of CIN is marked by increased transcriptional activity, evident by an almost 4-fold increase in mean RNA content obtained from our CIN samples versus normal cervical tissue. Furthermore, a number of statistically significant overexpressed genes of interest related to immune function/response and cell cycle control were identified in our pilot microarray study. This data have the ability to direct future research endeavors in cervical neoplasia. Future endeavors include the use of laser capture microdissection to evaluate genomic changes strictly at the epithelial level and, as such, exclude stromal response contributions.

Adult↗

PubMed1979

Comparison of receptive-field properties of X and Y ganglion cells with X and Y lateral geniculate cells in the cat.

1. To examine the transmission of visual information through the lateral geniculate nucleus, we have studied the receptive-field properties of 65 X and Y optic tract axons and compared them with the receptive-field properties of X and Y LGN cells in paralyzed cats anesthetized with N2O/O2 (70/30%). The same experimental conditions and quantitative methods have been used as in the preceding study of LGN cells (2). 2. The spatiotemporal organization of the receptive fields of X and Y retinal axons are similar to those of X and Y LGN cells. X ganglion cell receptive fields show a simple center-surround organization, whereas Y ganglion cell receptive fields show a more complex organization with three concentric regions: a central region of center-type response, a region of mixed center-type and surround-type responses, and a region of surround-type response. 3. The inhibitory strengh of the surrounding region was tested with a centrally located flashing light spot of successively increased diameter. As in the LGN, the inhibitory strenght of the surrounding region was stronger in retinal X-cells than in retinal Y-cells, and the strength of the inhibition decreased as the diameter of the receptive-field center increased. 4. The decrease of the inhibitory strength of the surrounding region with increasing distance from the receptive-field center was similar in the retina and in the LGN for cells belonging to the same class (X or Y) and having the same receptive-field center size. 5. The differences in properties in the LGN between small-field X-, large-field X-, and Y-cells are best explained by assuming that they are driven, respectively, by small-field X, large-field X, and Y retinal ganglion cells. There does not appear to be a significant mixing of properties either between cells having different receptive-field center sizes. 6. The principal transformation we found between retinal and LGN units is that X LGN cells have sharply lower spontaneous activities and driven activities, as compared with X ganglion cells. Y LGN units show only a small decrease in spontaneous activity in comparison with Y ganglion cells. 7. We conclude that there is a significant alteration in the LGN only in the properties of X-cells, possibly by way of a strong inhibitory pool converging on X LGN units. We further suggest that this inhibitory pool plays a role in the modulation of transmission of information through the LGN only in the X channel, while the Y channel appears to be relatively unaffected.

Animals↗

PubMed2000

The forkhead transcription factor UNC-130 is required for the graded spatial expression of the UNC-129 TGF-beta guidance factor in C. elegans.

Secreted proteins required for cellular movements along the circumference of the body wall in Caenorhabditis elegans include UNC-6/netrin and the novel TGF-beta UNC-129. Expression of these proteins is graded along the dorsoventral (D/V) axis, providing polarity information to guide migrations. Here we show that the graded expression of UNC-129 in dorsal but not ventral body muscles depends on unc-130, which encodes a Forkhead transcription factor. The phenotype of unc-130 mutants closely mimics the reported effects of ectopically expressing unc-129 in both dorsal and ventral body muscles (). This fits our present finding that unc-130 cell autonomously represses unc-129 expression in the ventral body muscles. Thus the cell-specific effects of unc-130 on ventral, but not dorsal, body muscle expression of unc-129 accounts for the D/V polarity information required for UNC-129-mediated guidance. Genetic interactions between unc-130 and other guidance genes show that several molecular pathways function in parallel to guide the ventral to dorsal migration of distal tip cells (DTCs) and axonal growth cones in C. elegans. Genetic interactions confirm that UNC-129 does not require the only known type II TGF-beta receptor in C. elegans (DAF-4) for its guidance functions. Also, unc-130 is partially required for male tail morphogenesis and for embryogenesis.

Amino Acid Sequence↗

PubMedDate not supplied

Transcriptomics and proteomics: tools for optimising phytoremediation activities.

Negligent industrial development has greatly contributed to environmental pollution through the contamination of water and soil by xenobiotic organic chemicals Remedial strategies to deal with chemical pollution require reliable methods to identify and monitor contamination, as well as effective procedures to attenuate or to eliminate the pollutant. In the food chain, plants are ideally placed as early bio-indicators of environmental pollution as they experience and respond to environmental toxicants sooner than organisms at higher trophic levels. Furthermore, some plants are capable of detoxifying anthropogenic chemicals by metabolic transformation and could prove useful for the remediation of contaminated water and soil: so-called phytoremediation. So far research technologies aimed at developing plants for bio-indication/bio-monitoring and for remediation have largely relied on standardised chemical and biochemical procedures to evaluate phytotoxicity, metabolic fate and persistence of organic pollutants in plants. The next stage in the evolution of these plant-based technologies is the improvement and optimisation of any innate phytoremediation activities identified in selected plants. In general, uptake followed by metabolism and compartmentation is responsible for the detoxification of organic xenobiotics in plants. These are complex cellular systems that may be organised in well-defined pathways and are often controlled by large families of genes. In order to elucidate complex traits such as detoxification, an emerging idea is to make use of global approaches such as the new "omic" technologies to identify molecular changes in plant tissues exposed to specific organic xenobiotics. From expression profiles at the messenger RNA level, transcriptomics permit the identification of function-related gene clusters and at the protein level proteomics provide information on where, when and at what level specific proteins accumulate. We conclude that these global approaches may be a useful way of widening screening capability to identify appropriate molecular markers that can be used to improve detoxification activity.

Arabidopsis↗

PubMed2004

Coding static natural images using spiking event times: do neurons cooperate?

To understand possible strategies of temporal spike coding in the central nervous system, we study functional neuromimetic models of visual processing for static images. We will first present the retinal model which was introduced by Van Rullen and Thorpe and which represents the multiscale contrast values of the image using an orthonormal wavelet transform. These analog values activate a set of spiking neurons which each fire once to produce an asynchronous wave of spikes. According to this model, the image may be progressively reconstructed from this spike wave thanks to regularities in the statistics of the coefficients determined with natural images. Here, we study mathematically how the quality of information transmission carried by this temporal representation varies over time. In particular, we study how these regularities can be used to optimize information transmission by using a form of temporal cooperation of neurons to code analog values. The original model used wavelet transforms that are close to orthogonal. However, the selectivity of realistic neurons overlap, and we propose an extension of the previous model by adding a spatial cooperation between filters. This model extends the previous scheme for arbitrary--and possibly nonorthogonal--representations of features in the images. In particular, we compared the performance of increasingly over-complete representations in the retina. Results show that this algorithm provides an efficient spike coding strategy for low-level visual processing which may adapt to the complexity of the visual input.

Action Potentials↗