Proc Natl Acad Sci U S A
April 2023
Living systems are intrinsically nonequilibrium: They use metabolically derived chemical energy to power their emergent dynamics and self-organization. A crucial driver of these dynamics is the cellular cytoskeleton, a defining example of an active material where the energy injected by molecular motors cascades across length scales, allowing the material to break the constraints of thermodynamic equilibrium and display emergent nonequilibrium dynamics only possible due to the constant influx of energy. Notwithstanding recent experimental advances in the use of local probes to quantify entropy production and the breaking of detailed balance, little is known about the energetics of active materials or how energy propagates from the molecular to emergent length scales.
View Article and Find Full Text PDFMultiplex assays of variant effect (MAVEs) are a family of methods that includes deep mutational scanning experiments on proteins and massively parallel reporter assays on gene regulatory sequences. Despite their increasing popularity, a general strategy for inferring quantitative models of genotype-phenotype maps from MAVE data is lacking. Here we introduce MAVE-NN, a neural-network-based Python package that implements a broadly applicable information-theoretic framework for learning genotype-phenotype maps-including biophysically interpretable models-from MAVE datasets.
View Article and Find Full Text PDFDNA replication in eukaryotic cells initiates from replication origins that bind the Origin Recognition Complex (ORC). Origin establishment requires well-defined DNA sequence motifs in Saccharomyces cerevisiae and some other budding yeasts, but most eukaryotes lack sequence-specific origins. A 3.
View Article and Find Full Text PDFAdvances in DNA sequencing have revolutionized our ability to read genomes. However, even in the most well-studied of organisms, the bacterium , for ≈65% of promoters we remain ignorant of their regulation. Until we crack this regulatory Rosetta Stone, efforts to read and write genomes will remain haphazard.
View Article and Find Full Text PDFDespite the central importance of transcriptional regulation in biology, it has proven difficult to determine the regulatory mechanisms of individual genes, let alone entire gene networks. It is particularly difficult to decipher the biophysical mechanisms of transcriptional regulation in living cells and determine the energetic properties of binding sites for transcription factors and RNA polymerase. In this work, we present a strategy for dissecting transcriptional regulatory sequences using in vivo methods (massively parallel reporter assays) to formulate quantitative models that map a transcription factor binding site's DNA sequence to transcription factor-DNA binding energy.
View Article and Find Full Text PDFGene regulation is one of the most ubiquitous processes in biology. However, while the catalog of bacterial genomes continues to expand rapidly, we remain ignorant about how almost all of the genes in these genomes are regulated. At present, characterizing the molecular mechanisms by which individual regulatory sequences operate requires focused efforts using low-throughput methods.
View Article and Find Full Text PDFCrenosoma vulpis and Eucoleus aerophilus are nematode parasites that can cause verminous pneumonia in wild carnivores. There is a paucity of information regarding the distribution of parasites in the lungs and the relationship between histopathological and parasitological diagnoses in naturally infected foxes. The objectives of this study were: first, to study the lobar and airway distribution of C.
View Article and Find Full Text PDFMeconium aspiration syndrome has been for many years an important cause of neonatal respiratory distress in newborn babies and sporadically reported in animals. This investigation was designed to study the ultrastructural and morphometric changes in the lungs of neonatal rats following the intratracheal inoculation of meconium. Seven-day-old Fischer-344 rats (n = 24) were randomly allocated in two groups.
View Article and Find Full Text PDFMeconium aspiration syndrome is a major contributor to neonatal respiratory distress in infants and it has been sporadically recognized in neonatal animals. This investigation was designed to study the short and long term effects of meconium and amniotic fluid in the lungs of neonatal rats. Seven-day-old rats (n = 123) divided in three groups were intratracheally inoculated with saline solution, amniotic fluid or meconium.
View Article and Find Full Text PDFIn many scientific disciplines, measurements are taken from films that have been exposed to energetic sources. Examples include radiographs where the source is an X-ray tube, autoradiography where the source is a radioactive isotope and electrophoresis gels where the source is an enhanced chemiluminescence reaction. In these situations it is of interest to quantify the darkening of the film and compute the strength of the source which in the cases of autoradiography and electrophoresis can be used to compute unknown concentrations of biochemicals.
View Article and Find Full Text PDFSphere-like structures are commonly measured for clinical or research purposes. We measured two diameters, the circumference (perimeter) and cross sectional area of 113 equine ovarian follicles in a water bath then determined the relationships between those measurements and the actual volume of fluid in the follicles. Cross-sectional area, diameter3 and area2/3 were all highly correlated with the volume of the structures and superior (p < 0.
View Article and Find Full Text PDFMol Cell Endocrinol
January 1998
Many previous studies of obese rodents documented biochemical changes in pancreatic islets that contribute to hyperinsulinemia in vivo. Those studies used heterogeneous populations of islets, although the size of islets from obese rats ranges from < 100 to > 500 microm. Here, functional and morphological changes in size-sorted (< 125 and > 250 microm diameter) islets from obese Zucker (fa/fa) rats were correlated.
View Article and Find Full Text PDFAlterations in the liver of male and female Sprague-Dawley rats fed PCB congener 153 (2,2',4,4',5,5'-hexachlorobiphenyl) at 0.5, 5, or 50 ppm concentrations in diets for 13 weeks were determined morphometrically. A dose-dependent increase in hepatocyte volume was detected; the cytoplasmic compartment contributed to the increase in cell volume in an overwhelming fashion.
View Article and Find Full Text PDFJ Environ Qual
October 1998
An outdoor, solar illuminated growth chamber with modulated UV-B enhancement, is described and its performance characterized. The chamber was clad with Teflon film that transmitted both UV-A and UV-B with little absorption and whose transmission did not change significantly over 1 yr. An array of UV-B emitting fluorescent tubes with cellulose diacetate filters provided additional UV-B radiation inside the chamber with little additional UV-A, while a similar chamber with unenergized tubes provided an ambient control.
View Article and Find Full Text PDFBackground: Taste buds on the pig tongue have been neither studied in detail nor quantified. We have counted the numbers of fungiform and vallate papillae, estimated their taste bud densities, and computed numbers of taste buds per volume of papilla on porcine tongue. Pig was chosen for this work because it is an omnivorous animal, and is one of the better models for study of nutrition-related problems in omnivorous human beings.
View Article and Find Full Text PDFObjective: To evaluate the osteogenic effect of differing volumes of autogenous cancellous bone graft (ACBG) placed into partial cortical defects of the ulna.
Animals: 15 healthy, mature Beagles.
Procedure: Weekly radiographic views of defects were obtained over 8 weeks and were analyzed for bone density by use of radiographic optical densitometry.
Mediators and mechanisms responsible for the inhibitory modulation of trout intestinal smooth muscle were examined using a series of putative mediators and substances known to modulate neurotransmission in mammalian systems. Frequency response relationships to transmural stimulation and concentration response relationships to 5-hydroxytryptamine, carbachol, and substance P were established on paired segments of rainbow trout intestinein vitro in the presence and absence of putative modulatory agents. Modulation of neurally-mediated contractions of trout intestine was achieved with dibutyryl cyclic AMP and forskolin, agents that increase intracellular levels of cyclic AMP.
View Article and Find Full Text PDFBackground: Pulmonary intravascular macrophages (PIMs) of sheep have a globular surface coat that facilitates endocytosis of tracer particles and Escherichia coli lipopolysaccharide, and is disrupted by the heparin and Brefeldin A treatments. The present study investigated the in vivo dynamics of the coat globules following heparin-mediated removal, and the mechanism of globule organization on the plasma membrane of PIMs in vitro.
Methods: Sheep were administered heparin at a dose of 50 IU/kg body weight IV, and euthanised at 30 min, 3, 6, 12, 48, and 120 hr (n = 2 for each treatment) after the treatment.
Twelve pregnant primiparous sows were catheterized on day 102 of gestation and randomly allocated to receive ACTH (days 112-113 of gestation [2d], days 105-parturition [10d]) or saline. At parturition the 3rd, 4th, 6th and 7th piglet born alive were sacrificed either at birth or at 6 h. The later group was fed bovine colostrum through a stomach tube at 30 min, 2 and 4 h of life.
View Article and Find Full Text PDFThe effects of altered water temperature in vivo on in vitro smooth muscle contractility of rainbow trout intestine were investigated. Temperature has a significant effect on receptor-mediated intestinal smooth muscle contractility in the rainbow trout. The efficacy of 5-HT, carbachol, and transmural stimulation increased with temperatures above 10°C, with an optimal increase at 15°C.
View Article and Find Full Text PDFA method for finding the stereotaxic coordinates of brain areas from actual brain sections is presented. It uses a digitizer connected to a computer to gather coordinates from photographs of brain sections. The coordinates are mathematically translated and rotated to yield stereotaxic atlas coordinates of the areas digitized.
View Article and Find Full Text PDFThe effects of altered temperature in vivo on in vitro smooth muscle contractility of rainbow trout intestine were investigated. Initial analysis of the data revealed a seasonal variation in the maximal tension of intestinal smooth muscle attainable with 5-hydroxytryptamine (serotonin), carbachol, KCl, and transmural stimulation in vitro. Peaks occurred in spring and troughs in autumn.
View Article and Find Full Text PDFThe qualitative and quantitative expression of major histocompatibility class II antigens was investigated in the absorptive epithelium of the duodenum, jejunum, and ileum from mice of C3H/He (H-2k haplotype) and C57BL/6 (H-2b haplotype) strains by peroxidase-antiperoxidase labelling and image analysis. Immunohistochemical labelling revealed that the expression of class II antigens was greatest in the ileum and decreased proximally towards the duodenum. The villus epithelium of the duodenum showed a granular staining pattern in the apices of some cells.
View Article and Find Full Text PDFSeven dogs with torn cruciate ligament were used to evaluate the "over-the-top" repair procedure, using instantaneous center of rotation (ICR). Normal and cruciate-torn stifles of dogs were radiographed before surgery, using an image intensifier videotape system. The injured stifle was reradiographed 6 weeks after surgery.
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