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At least 1,099 records · Page 61Linked to original sources
PubMed2007

Dioxin concentrations in sediments of the Baltic Sea--a survey of existing data.

Recent survey results for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, dioxins) in Baltic Sea sediments from Finland, Sweden and Denmark were merged with previously published Baltic Sea data. Regional distribution of concentration levels, differences in congener patterns, and temporal changes in sediment profiles were examined. One of the main objectives was to study if any major point sources for different PCDD/F congeners could be identified on a regional scale, based on sediment records. The survey confirmed the impact of chlorophenol production derived highly chlorinated PCDF-congeners on the total toxicity in sediments in the Gulf of Finland near the Kymijoki river estuary. Signatures of other point sources or combined point sources pertinent to specific industry branches or particular production processes (such as pulp bleaching, vinyl chloride production, thermal processes) may be discerned. However, the findings did not support any of the known point sources significantly influencing those congeners that are most abundant in Baltic herring and salmon. Instead, regional distributions in the Baltic Sea indicate that atmospheric deposition may act as a major source for those congeners and especially for 2,3,4,7,8-PeCDF. There were clear indications of declines in levels in sediment in some areas, but generally the levels of highly chlorinated PCDD/Fs on the northern coast of the Gulf of Finland were still high when compared with other areas of the Baltic Sea. Major areas with data gaps cover the south-eastern and eastern coastal regions of the Baltic Proper and the southern Gulf of Finland.

Benzofurans↗
PubMed2005

Manipulations of the mouse femoral nerve influence the accuracy of pathway reinnervation by motor neurons.

Previous studies using the femoral nerve model in both mice and rats have shown that regenerating motor axons prefer to reinnervate the terminal nerve branch to muscle versus a terminal nerve branch to skin, a process that has been termed preferential motor reinnervation (PMR). If end organ contact with muscle and skin is prevented, this preferential motor reinnervation still occurs in the rat. To better understand the process of preferential motor reinnervation in the mouse, we examined motor neuron reinnervation of muscle and cutaneous pathways without any end organ contact as well as with only cutaneous end organ contact. Surprisingly, there was no preferential motor reinnervation: Motor neurons preferred the cutaneous pathway over the muscle pathway when all end organ contact was prevented and showed an even greater preference for the cutaneous pathway when it was attached to skin.

Afferent Pathways↗
PubMed2026

A multi-modal survival prediction framework with group-based batch training and structural consistency alignment.

OBJECTIVE: Integrating whole-slide images (WSIs) with transcriptomic profiles is pivotal for enhancing cancer survival prediction. However, the intrinsic gigapixel resolution and variable sequence lengths of WSIs create a fundamental trade-off between training efficiency and the preservation of data heterogeneity in existing frameworks. Furthermore, substantial statistical and structural discrepancies between histological and genomic modalities often impede effective cross-modal alignment and fusion, thereby limiting prognostic accuracy. METHODS: We propose PRISM, an efficient multi-modal learning framework for integrating WSIs with transcriptomic profiles. To reconcile training efficiency with full data heterogeneity, PRISM first stochastically partitions variable-length WSI sequences into a main subset and a complementary residual subset, both of which are packed into fixed-length groups for batch training. The main subset is processed in the main branch, utilizing isolation masking to maintain intra-group sequence independence. Simultaneously, the residual subset is consolidated into "hyperslides" within a residual branch that leverages tailored supervision, effectively capturing inter-slide correlations. Furthermore, PRISM integrates an Informative Token Aggregation (ITA) module to reduce redundancy in WSIs and employs Cross-batch Structural Consistency Alignment (CBSCA) mechanism to enhance inter-modal structural connectivity. Finally, efficient cross-modal feature interaction is achieved through a Low-rank Bilinear Gated Fusion (LBGF) module. Code is available at https://github.com/Alisa2080/PRISM. RESULTS: Compared with existing methods, PRISM achieves the best overall C-index across five TCGA cohorts. On the larger TCGA-BRCA dataset, PRISM requires only 6 hours of training time, substantially reducing computational cost relative to strong multimodal baselines. Furthermore, comprehensive evaluations demonstrate that PRISM achieves the best overall IBS ranking and favorable time-dependent AUC performance at 1, 3, and 5 years, thereby delivering a more favorable trade-off between prognostic performance and computational efficiency. CONCLUSION: PRISM provides a favorable balance between predictive performance, calibration quality, and computational efficiency, highlighting its potential for practical deployment in multimodal survival modeling for computational pathology.

Humans↗
PubMed2006

The pathology of the heart conduction system in congenital heart block.

The incidence of congenital complete heart block is estimated in 1 of 2500-20,000 births. Many cases are isolated (found in an otherwise normal heart) and the pathology of the heart conduction system is variable. We report a 51-year-old man with the diagnosis of complete heart block, with a permanent pacemaker. No family history of rhythm disturbances was available. The patient presented and endocarditis after replacement of the pacemaker battery. The prognosis was poor and the patient died three months later. Autopsy examination showed signs of shock, of septic origin. The heart was hypertrophic (450g) and the left ventricle thickened. Histopathological examination of the heart conduction system showed that the sinus and atrioventricular nodes were normal, but the His bundle was interrupted and replaced by fibrous tissue. No inflammatory signs were present. Loss of conducting fibres and their replacement by fibrous tissue is the most common pathological process in complete heart block. In this case His bundle was mostly affected, different to Lev's disease where the process is more distal (branching atrioventricular bundle) and to Lenegre's disease, which shows a diffuse damage in the conducting system.

Autopsy↗
PubMed2004

Attenuation of glial scar formation in the injured rat brain by heparin oligosaccharides.

Injury to the central nervous system causes glial reactions, which eventually lead to the formation of a glial scar and inhibit axonal regeneration. The present study aimed to reduce the extent of glial scar formation in injured cerebral cortex using heparin hexasaccharide (6-mer) and octasaccharide (8-mer). A single injection of 20 microl of heparin 6-mer or heparin 8-mer (10mg/ml), native heparin (10mg/ml), or saline vehicle was given into the wound cavity just after cryo-injury in the cerebral cortex. In saline-injected control rats, strong chondroitin sulfate-A (CS-A) immunoreactivity using 2H6 antibody was observed around the injured site. Double labeling using an antibody against glial fibrillary acidic protein, a glial marker, further demonstrated that CS-A immunoreactivity was mainly expressed on the reactive astrocytes at the glial scar, indicating that CS-A immunohistochemistry is useful for evaluating glial scar formation. Quantitative morphometrical analysis revealed that the area of CS-A immunoreactivity was significantly decreased by 53% in heparin-6-mer-injected animals and 44% in heparin-8-mer-injected ones 6 days after the injury, but native heparin had no effect on CS-A-immunoreactive areas. Both heparin oligosaccharides also attenuated the intensity of CS-A immunoreactivity in the reactive astrocytes and caused astrocytic cellular processes to be less branched. These results demonstrate that a single injection of heparin oligosaccharides attenuates glial scar formation, indicating that heparin oligosaccharides may be applicable to many fibrotic diseases and restore functional integrity.

Animals↗
PubMed2004

The Caenorhabditis elegans aryl hydrocarbon receptor, AHR-1, regulates neuronal development.

The mammalian aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxic effects of dioxins and related compounds. Dioxins have been shown to cause a range of neurological defects, but the role of AHR during normal neuronal development is not known. Here we investigate the developmental functions of ahr-1, the Caenorhabditis elegans aryl hydrocarbon receptor homolog. We show that ahr-1:GFP is expressed in a subset of neurons, and we demonstrate that animals lacking ahr-1 function have specific defects in neuronal differentiation, as evidenced by changes in gene expression, aberrant cell migration, axon branching, or supernumerary neuronal processes. In ahr-1-deficient animals, the touch receptor neuron AVM and its sister cell, the interneuron SDQR, exhibit cell and axonal migration defects. We show that dorsal migration of SDQR is mediated by UNC-6/Netrin, SAX-3/Robo, and UNC-129/TGFbeta, and this process requires the functions of both ahr-1 and its transcription factor dimerization partner aha-1. We also document a role for ahr-1 during the differentiation of the neurons that contact the pseudocoelomic fluid. In ahr-1-deficient animals, these neurons are born but they do not express the cell-type-specific markers gcy-32:GFP and npr-1:GFP at appropriate levels. Additionally, we show that ahr-1 expression is regulated by the UNC-86 transcription factor. We propose that the AHR-1 transcriptional complex acts in combination with other intrinsic and extracellular factors to direct the differentiation of distinct neuronal subtypes. These data, when considered with the neurotoxic effects of AHR-activating pollutants, support the hypothesis that AHR has an evolutionarily conserved role in neuronal development.

Animals↗
PubMed2000

Chiral discotic columnar germs of nucleosome core particles.

In concentrated solution and in the presence of high concentrations of monovalent cations, nucleosome core particles order into a discotic columnar mesophase. This phase is limited to finite-sized hexagonal germs that further divide into six coiled branches, following an iterative process. We show how the structure of the germs comes from the competition between hexagonal packing and chirality with a combination of dendritic facetting and double-twist configurations. Geometrical considerations lead us to suspect that the chirality of the eukaryotic chromosomes may originate from the same competition.

Animals↗
PubMed1987

A method for defining steady-state unidirectional fluxes through branched chemical, osmotic and chemiosmotic reactions.

A general mathematical technique is described for deriving analytical expressions and obtaining numerical solutions for the steady-state unidirectional fluxes between two chemical states via any set of intermediate states present within any hypothetical system of unbranched or branched and overlapping elementary processes. The technique is a restricted application of the theory of Markov processes with conditional probabilities being assigned to the chemical state transitions constituting the system of reactions. While, in principle, the technique requires the summation of an infinite power series of a matrix defining the conditional probabilities of single state transitions, the power series is evaluated by means of the Taylor series expansion for matrices. As this technique allows isotopic exchange velocity equations to be derived from systems of reactions in which no distinction between the labelled and unlabelled species is required it provides a distinct and independent alternative to previously proposed methods. The technique is illustrated by application to a mechanism for second-order carrier-mediated transport.

Biological Transport↗
PubMedDate not supplied

Steps towards a European dioxin emission inventory.

The results of a project aiming at collection and evaluation of information regarding the industrial and non-industrial emission sources for dioxins and furans (PCDD/PCDF) in 17 European Countries (EU 15, CH, N) are presented. An overview about national documents covering dioxin emission inventories for the period 1990-1995 is given. Some data on emissions associated with residual materials, waste and waste water are presented additionally. Based on the air emission data contained in these documents the most important emission sources were determined which are assumed to cover about 90% of the overall emissions. For the selected sources and for all 17 countries new estimates of the atmospheric PCDD/PCDF emissions were derived from average emission factors and statistical activity rates for the year 1994. As a result, on the European scale the largest annual PCDD/PCDF emission is assessed to be released from municipal waste incineration, quite closely followed by emissions from iron ore sintering. Considerable releases of dioxins and furans--based, however, on highly uncertain data--are further assessed for domestic burning, accidental fires and (former) use of contaminated wood preservatives (pentachlorophenol). A lower but still significant emission is further assigned to the sector of non-ferrous metal production; particular processes used in this branch proved to generate very high PCDD/PCDF flue gas concentrations.

Air Pollutants↗
PubMed1998

Autocatalytic oxidation of hemoglobin by nitrite: a possible mechanism.

Oxidation of oxyhemoglobin by nitrite ions to produce methemoglobin is one of the more employed procedures to oxidize the hemoprotein. The process takes place readily after a clear induction time. This behaviour is usually explained in terms of an autocatalytic reaction mechanism. However, the generally accepted mechanism is not autocatalytic and cannot explain the main features of the process. In the present work it is proposed that the characteristics of the process require the occurrence of a fast reaction between oxyhemoglobin and nitrogen dioxide. This process acts as a branching step, leading to the observed autocatalysis.

Catalysis↗
PubMed1996

Unusual variants of the tributaries of the main pancreatic duct revealed by postmortem and endoscopic pancreatography.

Analysis of 97 human postmortem pancreatograms and 103 endoscopic pancreatograms revealed a total of 3 cases (1.5%) with isolated variants in the branches of the main pancreatic duct. In the first one, tortuous branches were present in the upper head-body region. The second case involved joint tributaries bridging over an unstenosed segment of the main pancreatic duct. In the third case, we found three branches from the uncinate process running down to the main duct. In all of these cases no pathological substrate was found, and they should be considered as anatomical variants observed during interpretation of a radiogram.

Adult↗
PubMed1995

Suicide substrates reveal properties of the homology-dependent steps during integrative recombination of bacteriophage lambda.

BACKGROUND: A fundamental feature of bacteriophage lambda site-specific recombination is the strict requirement for a region of sequence identity between recombining DNA duplexes. It has been difficult to understand how the recombination machinery identifies and responds to nonhomologies as subtle as a single base-pair substitution, because the reaction intermediates are transient and there are likely to be several different homology-dependent steps. In order to understand better how the recombination machinery compares parental sequences, we have used the recently developed 'suicide substances'--DNA containing 5'-bridging phosphorothioate linkages--to monitor the timing of homology-sensing relative to the strand cleavage reactions. RESULTS: The cleavage reactions for the two different strands of attB, the bacterial recombination locus for lambda integration, show very different degrees of dependence on homology with the partner locus, attP. Strand cleavage at the B binding site for Int recombinase is insensitive to homology. In contrast, cleavage at the B' binding site strongly depends on homology in the three base pairs adjacent to the B site. Strand cleavage at the B site is apparently required for the readout of this homology but, surprisingly, joining of the cleaved B site to a partner is not. CONCLUSIONS: Our finding that cleavage at the B site is insensitive to homology shows that effective synapsis between partners does not depend on sequence matching. Cleavage at the B' site provides the earliest positive signal for a homology-dependent switch in the lambda recombination machinery. Because this switch can occur in the absence of strand joining, the results argue against models that invoke strand ligation as the critical element of homology-sensing. Alternative mechanisms are presented that involve varieties of non-covalent strand swapping. A synthesis of the present results and other recent experiments highlights the importance of the disannealing of complementary strands and their reannealing to new partners, a process traditionally described as branch migration. The reversibility of branch migration and its bias away from mismatched combinations are proposed to be the major mechanisms of homology-sensing during lambda integration.

Bacteriophage lambda↗
PubMed1997

A new method for assessment of changes in retinal blood flow.

This study validates the use of residence time distribution (RTD) functions in human subjects to assess changes in retinal flow by using the widely recognized model of flow changes due to oxygen breathing. Changes in retinal blood flow may provide important information for clinical decision-making in several populations, including those with diabetic retinopathy, sickle cell disease and retinitis pigmentosa. Normal volunteer subjects were studied before and after oxygen breathing. After i.v. injection, relative fluorescence was obtained using scanning laser ophthalmoscopy/image processing in all vessel branches (average, 17). For each experiment, 64 frames (2/s) were digitized and were normalized using the RTD method. Vessel diameters were measured using densitometry techniques on fundus photos, where the diameter data made it possible to weight each vessel according to relative cross-sectional area to obtain a true mean circulation time (MCT). MCT increased for the group of subjects when breathing oxygen compared to normal air (P = 0.001), representing a decrease in retinal blood flow. Average MCT increased 2.82 +/- 2.51 s for all subjects, with an increase of 2.93 +/- 2.26 s in repeat trials for one subject. The proposed method uses information from all retinal vessels and allows the assessment of overall, as well as selected, regional retinal flow. It is more comprehensive than previous methods analysing single vessel flow. This method will be potentially useful for assessing hemodynamic changes in the retina associated with a wide range of eye disease.

Adult↗
PubMed2000

A three-step kinetic mechanism for peptide binding to MHC class II proteins.

Peptide binding reactions of class II MHC proteins exhibit unusual kinetics, with extremely slow apparent rate constants for the overall association (<100 M(-)(1) s(-)(1)) and dissociation (<10(-)(5) s(-)(1)) processes. Various linear and branched pathways have been proposed to account for these data. Using fluorescence resonance energy transfer between tryptophan residues in the MHC peptide binding site and aminocoumarin-labeled peptides, we measured real-time kinetics of peptide binding to empty class II MHC proteins. Our experiments identified an obligate intermediate in the binding reaction. The observed kinetics were consistent with a binding mechanism that involves an initial bimolecular binding step followed by a slow unimolecular conformational change. The same mechanism is observed for different peptide antigens. In addition, we noted a reversible inactivation of the empty MHC protein that competes with productive binding. The implications of this kinetic mechanism for intracellular antigen presentation pathways are discussed.

Antigens, Differentiation, B-Lymphocyte↗
PubMed2005

Tip-state control of rates and branching ratios in atomic manipulation.

We report the atomic manipulation properties of two distinct, stable, and reproducible states of a scanning tunneling microscope tip applied to chlorobenzene/Si(111)-(7x7). We show that the tip state influences the rates of (current-driven) molecular desorption and C-Cl dissociation as well as the branching ratio between these processes, but does not change the mediating electronic channel or the required number of electrons. These manipulation properties combined with the imaging properties of the two tip-states suggest the major difference between tip-states is their coupling efficiency to the pi-states of the chlorobenzene molecule.

Chlorobenzenes↗
PubMed2002

Coordinating early kidney development: lessons from gene targeting.

The kidney is widely used to study the mechanisms of organogenesis. Its development involves fundamental processes, such as epithelial branching, induced morphogenesis and cytodifferentiation, which are common to the development of many other organs. Gene-targeting experiments have greatly improved our understanding of kidney development, and have revealed many important genes that regulate early kidney organogenesis, some of which have a role in inherited human kidney disorders. Although our understanding of how the kidney is assembled is still limited, these studies are beginning to provide insights into the genetic and cellular interactions that regulate early organogenesis.

Allantois↗
PubMed2000

Endoplasmic reticulum (ER)-associated degradation of misfolded N-linked glycoproteins is suppressed upon inhibition of ER mannosidase I.

To examine the role of early carbohydrate recognition/trimming reactions in targeting endoplasmic reticulum (ER)-retained, misfolded glycoproteins for ER-associated degradation (ERAD), we have stably expressed the cog thyroglobulin (Tg) mutant cDNA in Chinese hamster ovary cells. We found that inhibitors of ER mannosidase I (but not other glycosidases) acutely suppressed Cog Tg degradation and also perturbed the ERAD process for Tg reduced with dithiothreitol as well as for gamma-carboxylation-deficient protein C expressed in warfarin-treated baby hamster kidney cells. Kifunensine inhibition of ER mannosidase I also suppressed ERAD in castanospermine-treated cells; thus, suppression of ERAD does not require lectin-like binding of ER chaperones calnexin and calreticulin to monoglucosylated oligosaccharides. Notably, the undegraded protein fraction remained completely microsome-associated. In pulse-chase studies, kifunensine-sensitive degradation was still inhibitable even 1 h after Tg synthesis. Intriguingly, chronic treatment with kifunensine caused a 3-fold accumulation of Cog Tg in Chinese hamster ovary cells and did not lead to significant induction of the ER unfolded protein response. We hypothesize that, in a manner not requiring lectin-like activity of calnexin/calreticulin, the recognition or processing of a specific branched N-linked mannose structure enhances the efficiency of glycoprotein retrotranslocation from the ER lumen.

Alkaloids↗
PubMedDate not supplied

Federal funding for AIDS research: decision process and results in fiscal year 1986.

With the history of the U.S. federal budget for fiscal year 1986 as a vehicle, the usual processes in the executive branch and the Congress that establish health research priorities and the unusual developments that have shaped priorities for AIDS are described. In the 3 years between the initial formulation of the AIDS budget and its execution, there were numerous revisions and evidence of poor communication between scientists and policy makers. On the basis of this analysis, two recommendations are made: the director of the National Institutes of Health and the heads of other U.S. Public Health Service agencies should have discretionary funds to use for AIDS activities; and better channels of communication between the Congress, the Public Health Service, and outside biomedical researchers should be established for consultation on priorities for AIDS research.

Acquired Immunodeficiency Syndrome↗