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At least 127 records · Page 7Linked to original sources
PubMed2000

Ultraviolet radiation and the photobiology of earth's early oceans.

During the Archean era (3.9-2.5 Ga ago) the earth was dominated by an oceanic lithosphere. Thus, understanding how life arose and persisted in the Archean oceans constitutes a major challenge in understanding early life on earth. Using a radiative transfer model of the late Archean oceans, the photobiological environment of the photic zone and the surface microlayer is explored at the time before the formation of a significant ozone column. DNA damage rates might have been approximately three orders of magnitude higher in the surface layer of the Archean oceans than on the present-day oceans, but at 30 m depth, damage may have been similar to the surface of the present-day oceans. However at this depth the risk of being transported to surface waters in the mixed layer was high. The mixed layer may have been inhabited by a low diversity UV-resistant biota. But it could have been numerically abundant. Repair capabilities similar to Deinococcus radiodurans would be sufficient to survive in the mixed layer. Diversity may have been greater in the region below the mixed layer and above the light compensation point corresponding to today's 'deep chlorophyll maximum'. During much of the Archean the air-water interface was probably an uninhabitable extreme environment for neuston. The habitability of some regions of the photic zone is consistent with the evidence embodied in the geologic record, which suggests an oxygenated upper layer in the Archean oceans. During the early Proterozoic, as ozone concentrations increased to a column abundance above 1 x 10(17) cm-2, UV stress would have been reduced and possibly a greater diversity of organisms could have inhabited the mixed layer. However, nutrient upwelling from newly emergent continental crusts may have been more significant in increasing total planktonic abundance in the open oceans and coastal regions than photobiological factors. The phohobiological environment of the Archean oceans has implications for the potential cross-transfer of life between other water bodies of the early Solar System, possibly on early Mars or the water bodies of a wet, early Venus.

DNA↗
PubMed2001

Mitochondrial versus nuclear gene sequences in deep-level mammalian phylogeny reconstruction.

Both mitochondrial and nuclear gene sequences have been employed in efforts to reconstruct deep-level phylogenetic relationships. A fundamental question in molecular systematics concerns the efficacy of different types of sequences in recovering clades at different taxonomic levels. We compared the performance of four mitochondrial data sets (cytochrome b, cytochrome oxidase II, NADH dehydrogenase subunit I, 12S rRNA-tRNA-16S rRNA) and eight nuclear data sets (exonic regions of alpha-2B adrenergic receptor, aquaporin, ss-casein, gamma-fibrinogen, interphotoreceptor retinoid binding protein, kappa-casein, protamine, von Willebrand Factor) in recovering deep-level mammalian clades. We employed parsimony and minimum-evolution with a variety of distance corrections for superimposed substitutions. In 32 different pairwise comparisons between these mitochondrial and nuclear data sets, we used the maximum set of overlapping taxa. In each case, the variable-length bootstrap was used to resample at the size of the smaller data set. The nuclear exons consistently performed better than mitochondrial protein and rRNA-tRNA coding genes on a per-residue basis in recovering benchmark clades. We also concatenated nuclear genes for overlapping taxa and made comparisons with concatenated mitochondrial protein-coding genes from complete mitochondrial genomes. The variable-length bootstrap was used to score the recovery of benchmark clades as a function of the number of resampled base pairs. In every case, the nuclear concatenations were more efficient than the mitochondrial concatenations in recovering benchmark clades. Among genes included in our study, the nuclear genes were much less affected by superimposed substitutions. Nuclear genes having appropriate rates of substitution should receive strong consideration in efforts to reconstruct deep-level phylogenetic relationships.

Animals↗
PubMed1996

Numerical simulation of environment modulation of chemical signal structure and odor dispersal in the open ocean.

Hydrodynamic models were used to simulate the dispersal of a model fish pheromone at three characteristic depth regimes (mixed layer, and 300 and 1000 m) of broad extent in the open ocean at the scale of individual organisms. The models were calibrated to experimental studies of dye dispersal at these depths and the goldfish pheromone system was used as the model odorant. There are profound differences in the time course and geometry of dispersing odor fields with depths. Below the thermocline odor fields spread primarily as horizontal patches with dispersal rates about five times slower at 1000 m as compared to 300 m. In the mixed layer, odors disperse rapidly in all directions and the maximum radial distance of spread of a physiologically active odor patch is less than half of the deep water value. Increases in the threshold sensitivity of olfactory receptors can greatly increase effective odor field size. Chemical signals impact the encounter dynamics among oceanic organisms by affecting the distance at which the target (emitting) individual is perceived. Perception distances due to olfactory cues can be significantly greater than for other senses in pelagic oceanic environments. Environment specific modulation of odor fields then affects the signal properties and therefore utility of chemoreception that, in turn, bear on encounter probabilities and transfer functions in oceanic ecosystems.

Animals↗
PubMed2026

A Deep Model Framework for Morphological Trait Imputation Across Taxonomic Groups.

Incomplete morphological trait data pose major hurdles for trait-based analyses, particularly when missing values, multicollinearity, and sparse sampling constrain inference. These issues limit our ability to quantify trait variation and explore broad patterns of functional differentiation across taxa. Here, we introduce FS-DeepRBFNet, which overcomes these pitfalls through integrating correlation-based feature selection with a dual-layer adaptive radial basis function (RBF) network. This end-to-end approach effectively reduces noise and captures both linear allometric trends and nonlinear morphological relationships. We tested the framework on a large species-level morphological trait dataset of Chinese birds and further validated its cross-taxon transferability using the Amphibian Database (Caudata). FS-DeepRBFNet consistently outperformed conventional methods such as KNN, Random Forest, and XGBoost, demonstrating superior predictive accuracy across multiple traits. Beyond improvements, the model revealed biologically interpretable trait associations and stable cross-taxon generalization. These results demonstrate that FS-DeepRBFNet provides a robust and biologically grounded solution for morphological trait prediction, enabling reliable imputation for comparative phylogenetics, functional ecology, and biodiversity forecasting in data-limited situations.

cross‐taxon transferability↗
PubMed2004

Membrane insertion of the N-terminal alpha-helix of equinatoxin II, a sea anemone cytolytic toxin.

Equinatoxin II (Eqt-II) is a member of the actinoporins, a unique family of cytotoxins comprising 20 kDa pore-forming proteins isolated from sea anemones. Actinoporins bind preferentially to lipid membranes containing sphingomyelin, and create cation-selective pores by oligomerization of three to four monomers. Previous studies have shown that regions of Eqt-II crucial for its cytolytic mechanism are an exposed aromatic cluster and the N-terminal region containing an amphipathic alpha-helix. In the present study, we have investigated the transfer of the N-terminal alpha-helix into the lipid membrane by the use of three mutants containing an additional tryptophan residue in different positions within the amphipathic alpha-helix (Ile18-->Trp, Val22-->Trp and Ala25-->Trp). The interaction of the mutants with different model systems, such as lipid monolayers, erythrocytes and ghost membranes, was extensively characterized. Intrinsic fluorescence measurements and the use of vesicles containing brominated phospholipids indicated a deep localization of the N-terminal amphipathic helix in the lipid bilayer, except for the case of Val22-->Trp. This mutant is stabilized in a state immediately prior to final pore formation. The introduction of additional tryptophan residues in the sequence of Eqt-II has proved to be a suitable approach to monitor the new environments that surround defined regions of the molecule upon membrane interaction.

Animals↗
PubMed1999

Evolution of a light-harvesting protein by addition of new subunits and rearrangement of conserved elements: crystal structure of a cryptophyte phycoerythrin at 1.63-A resolution.

Cryptophytes are unicellular photosynthetic algae that use a lumenally located light-harvesting system, which is distinct from the phycobilisome structure found in cyanobacteria and red algae. One of the key components of this system is water-soluble phycoerythrin (PE) 545 whose expression is enhanced by low light levels. The crystal structure of the heterodimeric alpha(1)alpha(2)betabeta PE 545 from the marine cryptophyte Rhodomonas CS24 has been determined at 1.63-A resolution. Although the beta-chain structure is similar to the alpha and beta chains of other known phycobiliproteins, the overall structure of PE 545 is novel with the alpha chains forming a simple extended fold with an antiparallel beta-ribbon followed by an alpha-helix. The two doubly linked beta50/beta61 chromophores (one on each beta subunit) are in van der Waals contact, suggesting that exciton-coupling mechanisms may alter their spectral properties. Each alpha subunit carries a covalently linked 15,16-dihydrobiliverdin chromophore that is likely to be the final energy acceptor. The architecture of the heterodimer suggests that PE 545 may dock to an acceptor protein via a deep cleft and that energy may be transferred via this intermediary protein to the reaction center.

Computer Graphics↗
PubMedDate not supplied

Magnetization transfer imaging of diffuse axonal injury following experimental brain injury in the pig: characterization by magnetization transfer ratio with histopathologic correlation.

PURPOSE: Our goal was to evaluate the use of the magnetization transfer ratio (MTR) in the detection of diffuse axonal injury (DAI) resulting from traumatic brain injury in a swine model. METHOD: DAI was created by applying a nonimpact, coronal plane, rotational acceleration to the heads of miniature swine (n = 4). GE imaging was performed with and without off-resonance MT saturation. Histologic correlation of axonal injury with MRI was performed 7 days postinjury. Thirty-one subcortical white matter regions and 10 deep white matter regions were selected for the direct comparison of histologic data and MTR measurements. RESULTS: Nineteen of 41 examined locations exhibited histologic evidence of axonal injury. The mean MTR in regions with axonal damage was significantly less than in regions without axonal damage. These changes were observed both in regions demonstrating high signal intensity on T2-weighted images (T2WI) (p <0.0001, n = 6) and in regions with no signal intensity change on T2WI (p < 0.05, n = 13). CONCLUSION: These results suggest that the measurement of MTR may have the potential for evaluation axonal damage in DAI following traumatic brain injury even when conventional T2WI does not demonstrate the lesion.

Animals↗
PubMed2002

RET and anisotropy measurements establish the proximity of the conserved Trp17 to Ile98 and Phe99 of tear lipocalin.

Previous studies suggest that the conserved Trp17 on strand A of TL has a role in lipocalin stability and interacts, directly or indirectly, with Ile98 and Phe99 on strand G to influence ligand binding. Here, we determined the proximity of Trp17 to Ile98 and Phe99. Time-resolved fluorescence experiments showed resonance energy transfer between tryptophans at positions 17 and 98. In addition, an exciton effect was discovered in CD experiments resulting from interactions of the excited states of these tryptophans. Fluorescence anisotropy values of mutants containing two tryptophans (positions 99/17 and 98/17) were lower than expected in the absence of RET, confirming that these residues are proximate in tear lipocalin. The data support a model of tear lipocalin in which Trp17 and Phe99 are close together deep in the cavity and participate in an internal hydrophobic cluster. Ile98 is proximate to Trp17 but faces toward the outside of the cavity and in the model is part of an external hydrophobic patch. Comparison with beta-lactoglobulin suggests that these motifs may have an important influence on protein stability and ligand binding in other members of the lipocalin family.

Amino Acid Sequence↗
PubMed2006

Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine.

Choline kinase, responsible for the phosphorylation of choline to phosphocholine as the first step of the CDP-choline pathway for the biosynthesis of phosphatidylcholine, has been recognized as a new target for anticancer therapy. Crystal structures of human choline kinase in its apo, ADP and phosphocholine-bound complexes, respectively, reveal the molecular details of the substrate binding sites. ATP binds in a cavity where residues from both the N and C-terminal lobes contribute to form a cleft, while the choline-binding site constitutes a deep hydrophobic groove in the C-terminal domain with a rim composed of negatively charged residues. Upon binding of choline, the enzyme undergoes conformational changes independently affecting the N-terminal domain and the ATP-binding loop. From this structural analysis and comparison with other kinases, and from mutagenesis data on the homologous Caenorhabditis elegans choline kinase, a model of the ternary ADP.phosphocholine complex was built that reveals the molecular basis for the phosphoryl transfer activity of this enzyme.

Adenosine Diphosphate↗
PubMed2004

BETR-World: a geographically explicit model of chemical fate: application to transport of alpha-HCH to the Arctic.

The Berkeley-Trent (BETR)-World model, a 25 compartment, geographically explicit fugacity-based model is described and applied to evaluate the transport of chemicals from temperate source regions to receptor regions (such as the Arctic). The model was parameterized using GIS and an array of digital data on weather, oceans, freshwater, vegetation and geo-political boundaries. This version of the BETR model framework includes modification of atmospheric degradation rates by seasonally variable hydroxyl radical concentrations and temperature. Degradation rates in all other compartments vary with seasonally changing temperature. Deposition to the deep ocean has been included as a loss mechanism. A case study was undertaken for alpha-HCH. Dynamic emission scenarios were estimated for each of the 25 regions. Predicted environmental concentrations showed good agreement with measured values for the northern regions in air, and fresh and oceanic water and with the results from a previous model of global chemical fate. Potential for long-range transport and deposition to the Arctic region was assessed using a Transfer Efficiency combined with estimated emissions. European regions and the Orient including China have a high potential to contribute alpha-HCH contamination in the Arctic due to high rates of emission in these regions despite low Transfer Efficiencies. Sensitivity analyses reveal that the performance and reliability of the model is strongly influenced by parameters controlling degradation rates.

Air Pollutants↗
PubMed1997

On the accuracy of an [18F]FDOPA compartmental model: evidence for vesicular storage of [18F]fluorodopamine in vivo.

The biological accuracy of a nonlinear compartmental model describing the in vivo kinetics of L-3,4-dihydroxy-6-[18F]fluorophenylalanine ([18F]FDOPA) metabolism was investigated. Tissue activities for [18F]FDOPA and its labeled metabolites 3-O-methyl-[18F]FDOPA ([18F]OMFD), 6-[18F]fluorodopamine ([18F]FDA), L-3,4-dihydroxy-6-[18F]fluorophenylacetic acid ([18F]FDOPAC), and 6-[18F]fluorohomovanillic acid ([18F]FHVA) were calculated using a plasma [18F]FDOPA input function, and kinetic constants estimated previously by chromatographic fractionation of 18F-labeled compounds in plasma and brain extracts from rat. Present data accurately reflected the measured radiochemical composition in rat brain for tracer circulation times past 10 min. We formulated the hypothesis that the discrepancy between calculated and measured fractions of [18F]FDOPA and the deaminated metabolite [18F]FDOPAC at times earlier than 10 min reflected storage of [18F]FDA in vesicles without monoamine oxidase. This hypothesis explained the initially rapid appearance of [18F]FDOPAC in striatum by delayed transfer of [18F]FDA from cytosol into vesicles. We conclude that the simpler model of [18F]FDOPA compartmentation is accurate when the cytosolic and vesicular fractions of [18F]FDA are at steady-state; the approach to equilibrium has a time constant of 15-30 min. The present model is valid for positron emission tomography studies of [18F]FDOPA metabolism in living brain.

Animals↗
PubMed1996

An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence.

It was demonstrated previously that abrupt transfer of vigorously aerated cultures of Mycobacterium tuberculosis to anaerobic conditions resulted in their rapid death, but gradual depletion of available O2 permitted expression of increased tolerance to anaerobiosis. Those studies used a model based on adaptation of unagitated bacilli as they settled through a self-generated O2 gradient, but the model did not permit examination of homogeneous populations of bacilli during discrete stages in that adaptation. The present report describes a model based on culture of tubercle bacilli in deep liquid medium with very gentle stirring that keeps them in uniform dispersion while controlling the rate at which O2 is depleted. In this model, at least two stages of nonreplicating persistence were seen. The shift into first stage, designated NRP stage 1, occurred abruptly at a point when the declining dissolved O2 level approached 1% saturation. This microaerophilic stage was characterized by a slow rate of increase in turbidity without a corresponding increase in numbers of CFU or synthesis of DNA. However, a high rate of production of glycine dehydrogenase was initiated and sustained while the bacilli were in this state, and a steady ATP concentration was maintained. When the dissolved O2 content of the culture dropped below about 0.06% saturation, the bacilli shifted down abruptly to an anaerobic stage, designated NRP stage 2, in which no further increase in turbidity was seen and the concentration of glycine dehydrogenase declined markedly. The ability of bacilli in NRP stage 2 to survive anaerobically was dependent in part on having spent sufficient transit time in NRP stage 1. The effects of four antimicrobial agents on the bacilli depended on which of the different physiologic stages the bacilli occupied at a given time and reflected the recognized modes of action of these agents. It is suggested that the ability to shift down into one or both of the two nonreplicating stages, corresponding to microaerophilic and anaerobic persistence, is responsible for the ability of tubercle bacilli to lie dormant in the host for long periods of time, with the capacity to revive and activate disease at a later time. The model described here holds promise as a tool to help clarify events at the molecular level that permit the bacilli to persist under adverse conditions and to resume growth when conditions become favorable. The culture model presented here is also useful for screening drugs for the ability to kill tubercle bacilli in their different stages of nonreplicating persistence.

Adenosine Triphosphate↗
PubMed1999

Theoretical comparison of two interstitial ultrasound applicators designed to induce cylindrical zones of tissue ablation.

Although interstitial techniques are invasive, they are still the first-line therapeutic modalities for certain types of tumour. They are mainly relevant to tumours that are either inoperable or located so deep that access is complicated. Of the various types of radiation that can be delivered by the interstitial route, ultrasound is the most suitable for deep heating. The study compares the efficacy of two types of applicator with respect to their ability to induce cylindrical zones of coagulation necrosis. The transducer of the first applicator is tubular, whereas the second is plane and can rotate around its axis. Both have an external diameter of 4 mm, are fitted with surface cooling systems and operate at 10.7 MHz and 14 W.cm-2. Comparison involves mathematical modelling of ablated tissue in the targeted area by resolving the bioheat transfer equation (BHTE) using an algorithm based on finite differences. The BHTE gives a temperature value from which the thermal dose can be determined. It is shown that tissue ablation by tubular transducers is slow, and, in consequence, perfusion disturbs the heating pattern: in vivo, irradiation with a tubular transducer lasting 1081 s would be required to ablate a tissue mass with a radius of 8 mm. The corresponding period using a rotating plane transducer with 20 firing angles is only 618 s. The mean exposure time of each shot lasts 31 +/- 7 s. Therefore perfusion would have much less impact in the case of therapy administered using a plane transducer than that using a tubular one.

Equipment Design↗
PubMed2026

Pretraining improves prediction of genomic datasets across species.

MOTIVATION: Recent studies suggest that deep neural network models trained on thousands of human genomic datasets can accurately predict genomic features, including gene expression and chromatin accessibility. However, training these models is computation- and time-intensive, and datasets of comparable size do not exist for most other organisms. RESULTS: Here, we identify modifications to an existing state-of-the-art model that improve model accuracy while reducing training time and computational cost. Using this streamlined model architecture, we investigate the ability of models pretrained on human genomic datasets to transfer performance to a variety of different tasks. Models pretrained on human data but fine-tuned on genomic datasets from diverse tissues and species achieved significantly higher prediction accuracy while significantly reducing training time compared to models trained from scratch, with Pearson correlation coefficients between experimental results and predictions as high as 0.8. Further, we found that including excessive training tasks decreased model performance and that this decrease could be partially but not completely rescued by fine-tuning. Thus, simplifying model architecture, applying pretrained models, and carefully considering the number of training tasks may be effective and economical techniques for building new models across data types, tissues, and species. AVAILABILITY AND IMPLEMENTATION: Code is available on GitHub and Figshare: https://github.com/optimizedlearning/genomicsML, https://doi.org/10.6084/m9.figshare.31796116.

Genomics↗
PubMed2004

The crystallographic structure of the aldose reductase-IDD552 complex shows direct proton donation from tyrosine 48.

The X-ray crystal structure of human aldose reductase (ALR2) in complex with the inhibitor IDD552 was determined using crystals obtained from two crystallization conditions with different pH values (pH 5 and 8). In both structures the charged carboxylic head of the inhibitor binds to the active site, making hydrogen-bond interactions with His110 and Tyr48 and electrostatic interactions with NADP+. There is an important difference between the two structures: the observation of a double conformation of the carboxylic acid moiety of the inhibitor at pH 8, with one water molecule interacting with the main configuration. This is the first time that a water molecule has been observed deep inside the ALR2 active site. Furthermore, in the configuration with the lower occupancy factor the difference electron-density map shows a clear peak (2.5sigma) for the H atom in the hydrogen bond between the inhibitor's carboxylic acid and the Tyr48 side-chain O atom. The position of this peak implies that this H atom is shared between both O atoms, indicating possible direct proton transfer from this residue to the inhibitor. This fact agrees with the model of the catalytic mechanism, in which the proton is donated by the Tyr48 hydroxyl to the substrate. These observations are useful both in drug design and in understanding the ALR2 mechanism.

Aldehyde Reductase↗
PubMed2005

Quantum chemical modeling of CO oxidation by the active site of molybdenum CO dehydrogenase.

The catalytic mechanism of molybdenum containing CO dehydrogenase has been studied using hybrid DFT methods with quite large chemical models. The recent high-resolution X-ray structure, showing the surprising presence of copper linked to molybdenum, was used as a starting point. A pathway was initially found with a low barrier for C-O bond formation and CO2 release. However, this pathway did not include the formation of any S-CO2 species, which had been suggested by experiments with an n-butylisocyanide inhibitor. When these SCO2 structures were studied they were found to lead to deep minima, making CO2 release much more difficult. A large effort was spent, including investigations of other spin states, varying the number of protons and electrons, adding water, etc., until a plausible pathway for S-C bond cleavage was found. In this pathway a water molecule is inserted in between molybdenum and the SCO2 group. Full catalytic cycles, including electron and proton transfers, are constructed both with and without S-C bond formation. When these pathways are extended to two full catalytic cycles it can be understood why the formation of the S-C bond actually makes catalysis faster, even though the individual step of CO2 release becomes much more difficult. These results agree well with experimental findings.

Aldehyde Oxidoreductases↗
PubMed1986

The temporalis myo-osseous flap: an experimental study.

The present paper investigates the anatomy and vascularization of the temporalis myo-osseous flap. This is a calvarial bone flap that employs temporalis muscle and its distal pericranial extension as a pedicle. In six human cadavers the flap was raised as an island on the anterior deep temporal artery after transecting the zygomatic arch and coronoid process. Maximal mobilization was thus obtained, allowing rotation of the flap into the mouth for intraoral reconstruction. The arc of rotation and potential surgical applications were noted. A comparative study of the temporalis myo-osseous flap and free calvarial bone graft was then conducted in a rabbit model. Vascularization of the calvarial bone flap was confirmed by technetium scintigraphy performed on the first postoperative day. The uptake of fluorochrome labels immediately after transfer verified the adequacy of the periosteal circulation in maintaining viability and new osteoid formation throughout the full thickness of calvarial bone. The transplantation of free calvarial bone grafts was followed by necrosis of most cellular elements. This was demonstrated by an absence of fluorochrome uptake up to 19 days postoperatively and a predominance of empty lacunae and nonviable marrow.

Animals↗
PubMed1998

[Pharmacokinetic aspects of mastitis therapy].

Treating mastitis in dairy cattle, most often antibiotics are used systemically or intracisternally, supported by influencing the inflammatory process with other measures. The success of systemic treatment is influenced by the bioavailability of the chemotherapeutic agent. Here, apart from the molecular size and protein binding, the fat-solubility of the active principle as well as its degree of ionisation play a major role. The degree of ionisation is determined by the isoelectric point (pKa) of the substance and by the pH-value of the surrounding medium. Thus, weak acids are mainly ionised in blood and cannot be transferred into udder tissue and milk. Weak bases react in the opposite way. Applied locally, the drug must not irritate the udder to secure deep diffusion into the glandular tissue. Therefore, topically administered drugs are formulated on an oily basis, also for longer prophylaxis during the dry-off-period. The pharmaceutic and pharmacokinetic relevance of the chemical and physical factors as well as the influence of the particle size of the active principle were demonstrated with benzylpenicillin potassium in the in vitro model of the isolated perfused bovine udder.

Animals↗