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At least 19 recordsLinked to original sources
PubMed1979

Responses of human and baboon arteries to prostaglandin endoperoxides and biologically generated and synthetic prostacyclin: their relevance to cerebral arterial spasm in man.

1 Isolated strips of human or baboon basilar, middle cerebral, vertebral or common carotid arteries were set up in an isolated organ bath or in a superfusion cascade system. 2 These arteries relaxed to prostacyclin but contracted to prostaglandin endoperoxide (PGH2). 3 Human and baboon isolated arteries also generated prostacyclin from exogenous endoperoxide (PGH2). 4 Human arteries generated prostacyclin 36 h post-mortem but not 40 h post-mortem. The biologically generated prostacyclin relaxed the basilar artery and overcame the contractile effects of PGH2. 5 Thromboxane A2-like activity generated during human platelet aggregation by arachidonic acid caused contractions of the human basilar artery. 6 Prostacyclin reversed contractions of human basilar arteries caused by an unidentified vasoconstrictor factor in cerebrospinal fluid obtained from patients with cerebral arterial vasospasm after subarachnoid haemorrhage following rupture of cerebral arterial aneurysms. 7. The above vasospasm may be due at least in part to disordered physiological control of the calibre of cerebral arteries caused by diminished synthesis of prostacyclin.

Animals↗
PubMed1992

Aplysia californica contains a novel 12-lipoxygenase which generates biologically active products from arachidonic acid.

Physiologic stimulation of identified neurons in ganglia of the marine mollusk, Aplysia californica, leads to the generation of arachidonic acid metabolites. Using various preparations of Aplysia nervous tissue, we have identified 12-lipoxygenase products including the inactive 12-hydroxyeicosatetraenoic acid (12-HETE) and the biologically active 12-ketoeicosatetraenoic acid (12-KETE) and 8-hydroxy-11(12)-epoxyeicosatrienoic acid (8-HEpETE). Each of these metabolites can be derived from the intermediate 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which can itself activate several identified neurons in Aplysia. In spite of conflicting results in studies of mammalian brain 12-lipoxygenase, Aplysia nervous tissue clearly contains an enzymatic activity which generates stereochemically pure 12(S)-HETE. This activity is destroyed by boiling and is sensitive to nonspecific lipoxygenase inhibitors but not to agents specific for other lipoxygenases or the cyclooxygenase enzyme. The Aplysia 12-lipoxygenase is highly enriched in neural tissue and is almost completely absent in the neural sheath, which is composed primarily of connective tissue and muscle. Preliminary purification has shown that, in contrast to the previously characterized 12-lipoxygenases, the Aplysia enzyme is associated with membrane fractions and is not found in the cytosol. Further studies are in progress to determine the kinetic properties and to define the cellular and subcellular distribution of this novel lipoxygenase.

Animals↗
PubMedDate not supplied

[Temporal characteristics of bacteriorhodopsin as a molecular biological generator of current].

Generation of electric potential difference by bacteriorhodopsin proteoliposomes incorporated into the phospholipid-impregnated collodion film has been studied. It is shown that illumination of this film by continuous light gives rise to the generation of an electric potential difference across the film (plus on the bacteriorhodopsin-free side), which can be as high as 300 mV. Short unsaturating flash inducing single turn-over of bacteriorhodopsin generates the potential difference which is a function of the flash intensity (70 mV at 3 mjoule light). The flash-induced photoelectric response consists of four phases. (1) Very fast (tau less than 1 microsec) generation of a potential difference (minus in the bacteriorhodopsin-free compartment). The amplitude of this phase is rather small (1--5 mV). (2) Fast phase of positive charging of the bacteriorhodopsin-free compartment (tau = 25--50 microsec). (3) Slow phase of positive charging of this compartment (tau = 6--12 msec) Amplitude of the second phase is to that of the third as 1 : 2. (4) A very slow phase of discharge of the flash-induced potential difference (tau = 1 sec at 10(8) ohm X cm2 film resistance). The third phase was specifically inhibited by La3+. Both the second and the third phases are decelerated by substitution of D2O in 4.5--5 and 2 times, respectively, while the amplitude of the first phase increases. Prolonged storage of the system in the dark (tua = 20--25 min) causes the decrease in the amplitudes of the second and the third phases as if the amount of active bacteriorhodopsin molecules were increased by factor 2. Such an inhibition was reversed by 30--60 sec illumination of the system. The dark adaptation is accompanied by some increase in the first phase amplitude. Comparison of these data with results of other studies on bacteriorhodopsin suggests that (1) the first phase is due to the photoinduced change in the retinal dipole; (2) the second phase corresponds to H+ transfer from Schiff base to the water solution in the proteoliposome interior; 3) the third phase represents H+ transfer from the incubation mixture to Schiff base; (4) the dark adaptation is a result of transition of photoelectrochemically active all-trans-retinal to the inactive 13-cis-retinal.

Bacteriorhodopsins↗
PubMed2025

Generation of Biologically Contained Marburg Virus.

Wild-type Marburg virus (MARV) can only be handled in biosafety level 4 facilities. By removing an essential gene from the virus genome, deficient virus particles can be generated that are only capable of replication if the missing gene product is provided in trans. As a result, these viruses are restricted to specific cell lines, making them safe to handle at lower biosafety levels. Here, we provide a detailed overview of how to generate MARV in which the VP30 gene has been replaced by a green fluorescent reporter gene, as well as how to use lentiviral transduction to create stable cell lines expressing MARV VP30. These cell lines can be used for the propagation and confinement of the resulting reporter virus.

Marburgvirus↗
PubMed1978

Rat intestinal 25-hydroxyvitamin D3- and 1alpha,25-dihydroxyvitamin D3-24-hydroxylase.

The 24-hydroxylation of 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3 occurs in vitro in rat intestinal homogenates. 1alpha,24,25-Trihydroxyvitamin D3 obtained by incubating 1alpha,25-dihydroxyvitamin D3 with rat intestinal homogenates was isolated and then identified by co-chromatography of the biologically generated material with synthetic 1alpha,24R,25-trihydroxyvitamin D3 on a high pressure liquid chromatography system and by ultraviolet spectroscopy, periodate cleavage, and mass spectroscopy. 24,25-Dihydroxyvitamin D3 obtained by incubating 25-hydroxyvitamin D3 with intestinal homogenates was identified by co-chromatography of the biologically generated material with authentic 24R,25-dihydroxyvitamin D3 on a high pressure liquid chromatography system and by periodate cleavage. Tissue distribution studies indicate that the process occurs in rat intestinal homogenates but not in rat muscle, liver, or fetal calvaria homogenates. Nephrectomy does not diminish the production of 1alpha,24,25-trihydroxyvitamin D3 in vivo while it reduces markedly, but does not eliminate, production of 24,25-dihydroxyvitamin D3.

Animals↗
PubMed1976

Reconstitution of biological molecular generators of electric current. H+-ATPase.

1. Generation of a transmembrane electric potential difference by oligomycin-sensitive ATPase complex, incorporated into spherical or planar phospholipid membrane, has been demonstrated. To this end, penetrating anion probe and direct voltmeter measurement of electric potential across phospholipid membrane were used. It was found that ATP-induced electric response is sensitive to oligomycin and protonophorous uncouplers. 2. The effect of variations in the phospholipid component of proteoliposomes on the electric generation was studied. It was revealed that the usage of mitochondrial phospholipids and phosphatidylethanolamine allows the highest values of membrane potential to be obtained in the case of ATPase proteoliposomes. In the case of cytochrome oxidase and bacteriorhodopsin proteoliposomes, phosphatidylserine was also shown to be quite suitable. Phosphatidylcholine was absolutely ineffective in all cases. 3. In proteoliposomes, containing both ATPase and bacteriorhodopsin, ATP and light induced generation of the electric field of the same direction. 4. In ATPase + cytochrome oxidase proteoliposomes, ATP hydrolysis and ascorbate oxidation was found to support electric generation of the same direction if cytochrome c was inside vesicles. Oxidation via external cytochrome c resulted in formation of electric field of the direction, opposite to that induced by ATP hydrolysis. 5. The data obtained in experiments with proteoliposomes of different types are discussed. The conclusion is made that conversion of energy of different resources into electric form is a common feature of membraneous energy transducers, which is in agreement with the Mitchellian principle of cellular energetics.

Adenosine Triphosphatases↗
PubMed1976

Reconstitution of biological molecular generators of electric current. Cytochrome oxidase.

1. Direct measurement of the electric current generation by cytochrome oxidase has been carried out. To this end, two procedures were used. The simpler one consists in formation of planar artificial membrane from the mixture of decane solution of soya bean phospholipids and beef heart cytochrome oxidase. Addition of cytochrome c and ascorbate to one of the two compartments separated by the cytochrome oxidase-containing planar membrane was found to result in a transmembrane electric potential difference being formed (plus on cytochrome c side of the membrane). Maximal values of potential differences obtained by this method were about 40 mV. Much higher potentials were observed when another ("photeoliposome-planar membrane") method was applied. In this case cytochrome oxidase was reconstituted with phospholipid to form proteoliposomes which adhered to planar phospholipid membrane in the presence of Ca2+ ions. Addition of cytochrome c and ascorbate to the proteoliposome-containing compartment gives rise to generation of an electric potential difference across the planar membrane, which reached 100 mV at a current of about 1 X 10(-11) A (minus in the proteoliposome-free compartment). The electromotive force of this generator was estimated as being about 0.2 V. If ascorbate and proteoliposomes were added into different compartments, a penetrating hydrogen atom carrier (phenazine methosulfate, (PMS) or tetramethyl-p-phenylenediamine (TMPD)) was required for a membrane potential to be formed. Generation of an electric potential difference of the opposite direction (plus in the proteoliposome-free compartment) was revealed in experiments with cytochrome oxidase proteoliposome containing cytochrome c in their interior. In this case, addition of PMS or TMPD was necessary. 2. In the suspension of cytochrome oxidase proteoliposome the uptake of a cationic penetrant (tetraphenyl phosphonium cation) was found to be coupled with electron transfer via external cytochrome c. Electron transfer via intraproteoliposomal cytochrome c induced the uptake of anionic penetrants (tetraphenyl borate and phenyldicarbaundecaborane anions). 3. All the above effects were sensitive to cyanide and protonophorous uncouplers. 4. In proteoliposomes containing both cytochrome oxidase and bacteriorhodopsin, the light- and oxidation-dependent generations of membrane potential have been revealed. 5. The data obtained are in agreement with Mitchell's idea of transmembrane electron flow in the cytochrome oxidase segment of the respiratory chain.

Animals↗
PubMed1979

Generation of biologic activity from the purified alpha-chain of C5.

The alpha- and beta-chains of the fifth component of human complement (C5) have been isolated and their physical and biologic properties have been characterized. After electrophoresis in SDS-poly-acrylamide slab gels, the chains were eluted from the gels and extensively dialyzed. The amino acid composition of each chain was then determined. On SDS-gels, the alpha-chain was PAS positive whereas the beta-chain revealed little or no staining. As a measure of chemotactic activity, the lysosomal enzyme-releasing activity of both chains was examined before and after trypsinization; activity resided almost entirely in the alpha subunit. Reconstitution of C5 from its isolated chains, followed by trypsinization resulted in slightly less activity than that from the individual alpha subunit. These findings provide direct support for previous evidence suggesting the biologic activity for neutrophils derives entirely from the alpha subunit of C5. This represents the first report of direct recovery of biologic activity from a purified subunit chain of C5.

Alkylation↗
PubMed1976

Reconstitution of Biological Molecular generators of electric current. Bacteriorhodopsin.

1. Photoinduced generation of electric current by bacteriorhodopsin, incorporated into the planar phospholipid membrane, has been directly measured with conventional electrometer techniques. 2. Two methods for bacteriorhodopsin incorporation have been developed: (a) formation of planar membrane from a mixture of decane solution of phospholipids and of the fraction of violet fragments of the Halobacterium halobium membrane (bacteriorhodopsin sheets), and (b) adhesion of bacteriorhodopsin-containing reconstituted spherical membranes (proteoliposomes) to the planar membrane in the presence of Ca2+ or some other cations. In both cases, illumination was found to induce electric current generation directed across the planar membrane, an effect which was measured by macroelectrodes immersed into electrolyte solutions on both sides of the membrane. 3. The maximal values of the transmembrane electric potential were of about 150 mV at a current of about 10(-11) A. The electromotive force measured by means of counterbalancing the photoeffect by an external battery, was found to reach the value of 300 mV. 4. The action spectrum of the photoeffect coincides with the bacteriorhodopsin absorption spectrum (maximum about 570 nm). 5. Both components of the electrochemical potential of H+ ions (electric potential and delta pH) across the planar membrane affect the bacteriorhodopsin photoelectric response in a fashion which could be expected if bacteriorhodopsin were a light-dependent electrogenic proton pump. 6. La3+ ions were shown to inhibit operation of those bacteriorhodopsin which pump out H+ ions from the La3+-containing compartment. 7. The photoeffect, mediated by proteoliposomes associated with thick planar membrane, is decreased by gramicidin A at concentrations which do not influence the planar membrane resistance in the light. On the contrary, a protonophorous uncoupler, trichlorocarbonylcyanidephenylhydrazone, decreases the photoeffect only if it is added at a concentration lowering the light resistance. The dark resistance is shown to be higher than the light one, and decreases to the light level by gramicidin. 8. A simple equivalent electric scheme consistent with the above results has been proposed.

Bacteriorhodopsins↗
PubMed1976

Reconstitution of biological molecular generators of electric current. Bacteriochlorophyll and plant chlorophyll complexes.

1. Electric generation by bacteriochlorophyll reaction center complexes from Rhodospirillum rubrum and by photosystem I complexes from pea chloroplasts has been studied. 2. The methods for the proteoliposome reconstitution from azolectin and bacteriochlorophyll- or plant chlorophyll-containing protein complexes have been elaborated. Light-dependent electric responses of the proteoliposomes were detected using (a) phenyldicarbaundecarborane anion (PCB-) probe and (b) direct measurement by a voltmeter in the proteoliposome-planar phospholipid membrane system. 3. Both PCB- and direct measurements demonstrated that bacteriochlorophyll proteoliposomes are competent in light-dependent electric generation (plus outside proteoliposomes). The photoelectric effect was shown to increase on addition of tetramethyl-p-phenylenediamine (TMPD), CoQ6, and vitamin K3, and to decrease on addition of ferricyanide, o-phenanthroline and a protonophorous uncoupler. Estimation of the photoelectromotive force of the bacteriochlorophyll proteoliposome-planar membrane system gave a value of about 0.2 V. The action spectrum of the photoelectric effect was similar to the absorption spectrum of the bacteriochlorophyll complex. 4. Reconstitution of proteoliposomes containing bacteriochlorophyll centers and bacteriorhodopsin resulted in the system generating an electric field whose direction can be changed by varying the spectral composition of the light: the red light, exciting bacteriochlorophyll, induces negative, and the green light, exciting bacteriorhodopsin, induces positive charging of the proteoliposome interior. 5. Association of isolated R. rubrum chromatophores with planar phospholipid membrane was found to give a system demonstrating light-induced electric generation as high as 215 mV in the presence of napthoquinone, TMPD (or phenazine methosulfate, PMS), and ascorbate. Under the same conditions, addition of inorganic pyrophosphate or ATP results in formation of an electric field of the same direction as that induced by light. 6. Proteoliposomes with plant chlorophyll complexes of photosystem I demonstrated light-induced PCB- responses indicating formation of the electric field with plus inside vesicles. The effect required PMS addition. A protonophorous uncoupler and o-phenanthroline were inhibitory. Electric responses in the chlorophyll proteoliposome-planar membrane system were very small (not higher than 10 mV).

Bacterial Chromatophores↗
PubMed2026

Deep generative models in biological sequence and structure analysis and design.

Deep generative models have transformed biological sequence modeling from predictive analysis toward increasingly controllable design. Early biological applications of Variational Autoencoders (VAEs) and Generative Adversarial Networks (GANs) established latent representation learning and sequence synthesis, while recent advances in transformer-based language models, discrete diffusion, flow-matching, and multimodal generative frameworks have substantially expanded the scope of biological design. This review examines generative models for DNA, RNA, and protein sequence design, emphasizing how different model classes represent biological constraints, operate over discrete and continuous spaces, and integrate sequence, structure, and function. We compare VAEs, GANs, autoregressive and masked language models, diffusion models, and flow-based approaches across genomics, transcriptomics, and proteomics, with particular attention to controllability, long-range dependency modeling, structural grounding, generalization, and experimental utility. We further examine evaluation strategies, out-of-distribution generalization, and closed-loop design-build-test-learn workflows that connect in silico generation with empirical validation. We distinguish fundamental modality-dependent constraints including sequence discreteness, context length, structural coupling, and physical or thermodynamic requirements from architecture-dependent advantages that reflect the current state of the field. Current studies suggest that long-context models are particularly useful for genome-scale representation and sequence modeling, whereas structure-aware diffusion, flow-based, and inverse-folding approaches provide better frameworks for geometry-constrained RNA and protein design. This perspective provides a critical framework for understanding the present capabilities, limitations, and convergence of generative approaches toward reliable and experimentally grounded biological design.

Biological sequence analysis↗
PubMed2026

The Rise of Plant Pan-Genomes: From Genome Variation to Predictive Breeding.

Plant pan-genomics is entering a new phase beyond genome variation discovery, requiring a shift from cataloguing genomic diversity toward understanding how variation generates biological function and breeding value. Here, we propose that the future of plant pan-genomics will be shaped by three conceptual transitions. First, structural variation (SV), presence-absence variation (PAV), and haplotype diversity should be interpreted not merely as genomic differences, but as regulatory components that influence gene networks, chromatin organization, and complex traits. Second, the expansion from species-level pan-genomes to genus-level super pan-genomes provides an evolutionary framework for uncovering adaptive genetic modules preserved in wild relatives and overlooked during domestication. Third, integrating pan-genomes with pan-omics, three-dimensional genome analyses, and artificial intelligence will enable the transformation of genomic variation into predictive models for crop improvement. We further propose that the ultimate value of pan-genomes lies not in generating increasingly complete genome collections, but in establishing a mechanistic bridge between genome diversity, biological function, and breeding decisions. This transition will move crop improvement from empirical selection toward rational genome design, where evolutionary diversity can be systematically interpreted, predicted, and engineered.

Journal Article↗
PubMed2025

vcfsim: flexible simulation of all-sites VCFs with missing data.

BACKGROUND |: VCFs are the most widely used data format for encoding genetic variation. By design, standard VCFs do not include data from sites where all individuals are homozygous for the reference allele ("invariant sites") and thus do not differentiate these from sites where data are completely missing. However, missing data are a key feature of biological datasets across all domains of genomics, and many recent studies have shown that missing data can introduce a variety of statistical biases in the estimation of key population genetic parameters. A solution to this limitation is to include invariant sites in a standard VCF, creating an "all-sites VCF", exposing missing and invariant sites explicitly. One hurdle to the wider adoption of all-sites VCFs is a reliable parameterized simulation framework for generating biologically realistic all-sites VCFs. RESULTS |: Here, we introduce an open-source command line tool, vcfsim, that interfaces with the popular coalescent simulation platform msprime and provides convenience functions for simulating all-sites VCFs with variable levels of ploidy and missing data. We show that the post-processed VCFs generated using vcfsim align precisely with population genetic expectations (i.e. are statistically identical to raw msprime output), accurately introduce missing data, and permit the simulation of data with varying ploidy levels, including the simulation of intraindividual ploidy variation (e.g. heterogametic sex chromosomes) and population structures. CONCLUSIONS |: Our results vcfsim is a useful and easy-to-use tool for the benchmarking of new software tools, performing population genetic inference, training of machine learning models, and the exploration of the effects of missing data in genomics data sets.

Benchmarking↗
PubMed1992

Estimates for ELF effects: noise-based thresholds and the number of experimental conditions required for empirical searches.

Interactions between physical fields and biological systems present difficult conceptual problems. Complete biological systems, even isolated cells, are exceedingly complex. This argues against the pursuit of theoretical models, with the possible consequence that only experimental studies should be considered. In contrast, electromagnetic fields are well understood. Further, some subsystems of cells (viz. cell membranes) can be reasonably represented by physical models. This argues for the pursuit of theoretical models which quantitatively describe interactions of electromagnetic fields with that subsystem. Here we consider the hypothesis that electric fields, not magnetic fields, are the source of interactions, From this it follows that the cell membrane is a relevant subsystem, as the membrane is much more resistive than the intra- or extracellular regions. A general class of interactions is considered: electroconformational changes associated with the membrane. Expected results of such as approach include the dependence of the interaction on key parameters (e.g., cell size, field magnitude, frequency, and exposure time), constraints on threshold exposure conditions, and insight into how experiments might be designed. Further, because it is well established that strong and moderate electric fields interact significantly with cells, estimates of the extrapolated interaction for weaker fields can be sought. By employing signal-to-noise (S/N) ratio criteria, theoretical models can also be used to estimate threshold magnitudes. These estimates are particularly relevant to in vitro conditions, for which most biologically generated background fields are absent. Finally, we argue that if theoretical model predictions are unavailable to guide the selection of experimental conditions, an overwhelmingly large number of different conditions will be needed to find, establish, and characterize bioelectromagnetic effects in an empirical search. This is contrasted with well-established chemical dosimetry, which is much simpler. Because of the large number of possible electromagnetic field conditions, we also conclude that in vitro studies, rather than in vivo studies, should be emphasized in studies aimed at discovering and characterizing mechanisms for bioelectromagnetic effects.

Cell Membrane↗
PubMed2025

CountASAP: a lightweight, easy to use python package for processing ASAPseq data.

BACKGROUND: Declining sequencing costs coupled with the increasing availability of easy-to-use kits for the isolation of DNA and RNA transcripts from single cells have driven a rapid proliferation of studies centered around genomic and transcriptomic data. Simultaneously, a wealth of new techniques have been developed that utilize single cell technologies to interrogate a broad range of cell-biological processes. One recently developed technique, transposase-accessible chromatin with sequencing (ATAC) with select antigen profiling by sequencing (ASAPseq), provides a combination of chromatin accessibility assessments with measurements of cell-surface marker expression levels. While software exists for the characterization of these datasets, there currently exists no tool explicitly designed to reformat ASAP surface marker FASTQ data into a count matrix which can then be used for these downstream analyses. RESULTS: To address this lack of a dedicated tool for ASAPseq data processing, we created CountASAP, an easy-to-use Python package purposefully designed to transform FASTQ files from ASAP experiments into count matrices compatible with commonly-used downstream bioinformatic analysis packages. CountASAP takes advantage of the independence of the relevant data structures to perform fully parallelized matches of each sequenced read to user-supplied input ASAP oligos and unique cell-identifier sequences. We directly compare the performance and user-friendliness of CountASAP to existing tools using similarly-structured data from a more common sequencing experiment: cellular indexing of transcriptomes and epitopes by sequencing (CITEseq). Further benchmarking against existing tools helps to identify proper defaults for CountASAP and assess the agreement of outputs from all tested software. A final test using a novel ASAPseq dataset provides evidence that CountASAP can generate biologically meaningful results that correlate well with paired chromatin accessibility data. CONCLUSIONS: CountASAP shows good agreement with existing, well-tested data processing tools in the analysis of similarly-structured benchmarking data. CountASAP runs efficiently on a standard laptop, has user-friendly documentation, a one-step installation, and represents the first and only tool designed specifically for the processing of ASAPseq data.

Software↗
PubMed1977

Effect of tetramethyl lead on freshwater green algae.

The toxicity of tetramethyl lead (Me4Pb) towards freshwater algae was studied by bubbling biologically generated Me4Pb from one flask containing 5 mg of Pb 1-1 as Me3PbOAc into the culture medium in another flask where a test alga Scenedesmus quadricauda was grown. As Me4Pb is not soluble in water and is volatile, the exposure of an alga to this lead compound was only momentary. It was estimated that less than 0.5 mg of Pb(Me4Pb) had passed through the culture medium. The primary productivity and cell growth (determined by dry weight), however, decreased by 85% and 32% respectively, as compared with the controls without exposure to Me4Pb. Furthermore, cells exposed to Me4Pb tended to clump together and striking alterations in cell fine-structure were observed. An electron microscopic analysis by an energy dispersive spectrometer revealed that Pb ions had penetrated the cell and were deposited within concretion bodies. Similar results were obtained with the green algae Ankistrodesmus falcatus and Chlorella pyrenoidosa.

Aeromonas↗