Carbon dioxide and fruit odor transduction in Drosophila olfactory neurons. What controls their dynamic properties?

We measured frequency response functions between odorants and action potentials in two types of neurons in Drosophila antennal basiconic sensilla. CO2 was used to stimulate ab1C neurons, and the fruit odor ethyl butyrate was used to stimulate ab3A neurons. We also measured frequency response functions for light-induced action potential responses from transgenic flies expressing H134R-channelrhodopsin-2 (ChR2) in the ab1C and ab3A neurons. Frequency response functions for all stimulation methods were well-fitted by a band-pass filter function with two time constants that determined the lower and upper frequency limits of the response. Low frequency time constants were the same in each type of neuron, independent of stimulus method, but varied between neuron types. High frequency time constants were significantly slower with ethyl butyrate stimulation than light or CO2 stimulation. In spite of these quantitative differences, there were strong similarities in the form and frequency ranges of all responses. Since light-activated ChR2 depolarizes neurons directly, rather than through a chemoreceptor mechanism, these data suggest that low frequency dynamic properties of Drosophila olfactory sensilla are dominated by neuron-specific ionic processes during action potential production. In contrast, high frequency dynamics are limited by processes associated with earlier steps in odor transduction, and CO2 is detected more rapidly than fruit odor

A large conductance, Ca2+-activated K+ channel in a human lung epithelial cell line (A549)

AbstractA large conductance, Ca2+-activated K+ channel in a human lung epithelial cell line (A549) was identified using the single channel patch clamp technique. Channel conductance was 242±33 pS (n=67) in symmetrical KCl (140 mM). The channel was activated by membrane depolarization and increased cytosolic Ca2+. High selectivity was observed for K+ over Rb+(0.49)>Cs+(0.14)>Na+(0.09). Open probability was significantly decreased by Ba2+ (5 mM) and quinidine (5 mM) to either surface, but TEA (5 mM) was only effective when added to the external surface. All effects were reversible. Increasing cytosolic Ca2+ concentration from 10−7 to 10−6 M caused an increase in open probability from near zero to fully activated. ATP decreased open probability at ∼2 mM, but the effect was variable. The channel was almost always observed together with a smaller conductance channel, although they could both be seen individually. We conclude that A549 cells contain large conductance Ca2+-activated K+ channels which could explain a major fraction of the K+ conductance in human alveolar epithelial membranes

Design of the Data Description Language Processor

The Data Description Language (DDL) is a language for describing the structure of data, and expressing transformations that are to be performed on that data. The DDL Processor is a set of computer programs which interprets DDL statements and generates a computer program to perform the specified transformations. Together the DDL and its Processor provide a utility which can be used to perform jobs such as creating new data bases, reorganizing or extracting data from existing data bases, moving data to different storage devices, interfacing files between different programming languages, or between different operating systems. This report documents the design of the DDL Processor. Special features of the design include the use of special purpose internal languages, compiler-compiler techniques, bootstrapping methods, and a descriptor tree which aids in the parsing of input data

Stoichiometric and Stable Isotope Ratios of Wild Lizards in an Urban Landscape Vary with Reproduction, Physiology, Space and Time

Spatial and temporal variation in stoichiometric and stable isotope ratios of animals contains ecological information that we are just beginning to understand. In both field and lab studies, stoichiometric or isotopic ratios are related to physiological mechanisms underlying nutrition or stress. Conservation and ecosystem ecology may be informed by isotopic data that can be rapidly and non-lethally collected from wild animals, especially where human activity leaves an isotopic signature (e.g. via introduction of chemical fertilizers, ornamental or other non-native plants or organic detritus). We examined spatial and temporal variation in stoichiometric and stable isotope ratios of the toes of Uta stansburiana (side-blotched lizards) living in urban and rural areas in and around St. George, Utah. We found substantial spatial and temporal variation as well as context-dependent co-variation with reproductive physiological parameters, although certain key predictions such as the relationship between δ15N and body condition were not supported. We suggest that landscape change through urbanization can have profound effects on wild animal physiology and that stoichiometric and stable isotope ratios can provide unique insights into the mechanisms underlying these processes

Prevalence of liver fluke (Fasciola hepatica) in wild Red Deer (Cervus elaphus): coproantigen ELISA is a practicable alternative to faecal egg counting for surveillance in remote populations

Red deer (Cervus elaphus) are hosts of liver fluke (Fasciola hepatica); yet, prevalence is rarely quantified in wild populations. Testing fresh samples from remote regions by faecal examination (FE) can be logistically challenging; hence, we appraise frozen storage and the use of a coproantigen ELISA (cELISA) for F. hepatica surveillance. We also present cELISA surveillance data for red deer from the Highlands of Scotland. Diagnoses in faecal samples (207 frozen, 146 fresh) were compared using a cELISA and by FE. For each storage method (frozen or fresh), agreement between the two diagnostics was estimated at individual and population levels, where population prevalence was stratified into cohorts (e.g., by sampling location). To approximate sensitivity and specificity, 65 post-slaughter whole liver examinations were used as a reference. At the individual level, FE and cELISA diagnoses agreed moderately (κfrozen = 0.46; κfresh = 0.51), a likely reflection of their underlying principles. At the population level, FE and cELISA cohort prevalence correlated strongly (Pearson’s R = 0.89, p < 0.0001), reflecting good agreement on relative differences between cohort prevalence. In frozen samples, prevalence by cELISA exceeded FE overall (42.8% vs. 25.8%) and in 9/12 cohorts, alluding to differences in sensitivity; though, in fresh samples, no significant difference was found. In 959 deer tested by cELISA across the Scottish Highlands, infection prevalence ranged from 9.6% to 53% by sampling location. We highlight two key advantages of cELISA over FE: i) the ability to store samples long term (frozen) without apparent loss in diagnostic power; and ii) reduced labour and the ability to process large batches. Further evaluation of cELISA sensitivity in red deer, where a range of fluke burdens can be obtained, is desirable. In the interim, the cELISA is a practicable diagnostic for F. hepatica surveillance in red deer, and its application here has revealed considerable geographic, temporal, sex and age related differences in F. hepatica prevalence in wild Scottish Highland red deer

The Second Conference on Lunar Bases and Space Activities of the 21st Century, volume 1

These papers comprise a peer-review selection of presentations by authors from NASA, LPI industry, and academia at the Second Conference (April 1988) on Lunar Bases and Space Activities of the 21st Century, sponsored by the NASA Office of Exploration and the Lunar Planetary Institute. These papers go into more technical depth than did those published from the first NASA-sponsored symposium on the topic, held in 1984. Session topics covered by this volume include (1) design and operation of transportation systems to, in orbit around, and on the Moon, (2) lunar base site selection, (3) design, architecture, construction, and operation of lunar bases and human habitats, and (4) lunar-based scientific research and experimentation in astronomy, exobiology, and lunar geology

The Second Conference on Lunar Bases and Space Activities of the 21st Century, volume 2

These 92 papers comprise a peer-reviewed selection of presentations by authors from NASA, the Lunar and Planetary Institute (LPI), industry, and academia at the Second Conference on Lunar Bases and Space Activities of the 21st Century. These papers go into more technical depth than did those published from the first NASA-sponsored symposium on the topic, held in 1984. Session topics included the following: (1) design and operation of transportation systems to, in orbit around, and on the Moon; (2) lunar base site selection; (3) design, architecture, construction, and operation of lunar bases and human habitats; (4) lunar-based scientific research and experimentation in astronomy, exobiology, and lunar geology; (5) recovery and use of lunar resources; (6) environmental and human factors of and life support technology for human presence on the Moon; and (7) program management of human exploration of the Moon and space

Generation of orthotopic patient-derived xenografts from gastrointestinal stromal tumor.

BackgroundGastrointestinal stromal tumor (GIST) is the most common sarcoma and its treatment with imatinib has served as the paradigm for developing targeted anti-cancer therapies. Despite this success, imatinib-resistance has emerged as a major problem and therefore, the clinical efficacy of other drugs has been investigated. Unfortunately, most clinical trials have failed to identify efficacious drugs despite promising in vitro data and pathological responses in subcutaneous xenografts. We hypothesized that it was feasible to develop orthotopic patient-derived xenografts (PDXs) from resected GIST that could recapitulate the genetic heterogeneity and biology of the human disease.MethodsFresh tumor tissue from three patients with pathologically confirmed GISTs was obtained immediately following tumor resection. Tumor fragments (4.2-mm3) were surgically xenografted into the liver, gastric wall, renal capsule, and pancreas of immunodeficient mice. Tumor growth was serially assessed with ultrasonography (US) every 3-4 weeks. Tumors were also evaluated with positron emission tomography (PET). Animals were sacrificed when they became moribund or their tumors reached a threshold size of 2500-mm3. Tumors were subsequently passaged, as well as immunohistochemically and histologically analyzed.ResultsHerein, we describe the first model for generating orthotopic GIST PDXs. We have successfully xenografted three unique KIT-mutated tumors into a total of 25 mice with an overall success rate of 84% (21/25). We serially followed tumor growth with US to describe the natural history of PDX growth. Successful PDXs resulted in 12 primary xenografts in NOD-scid gamma or NOD-scid mice while subsequent successful passages resulted in 9 tumors. At a median of 7.9 weeks (range 2.9-33.1 weeks), tumor size averaged 473 ± 695-mm³ (median 199-mm3, range 12.6-2682.5-mm³) by US. Furthermore, tumor size on US within 14 days of death correlated with gross tumor size on necropsy. We also demonstrated that these tumors are FDG-avid on PET imaging, while immunohistochemically and histologically the PDXs resembled the primary tumors.ConclusionsWe report the first orthotopic model of human GIST using patient-derived tumor tissue. This novel, reproducible in vivo model of human GIST may enhance the study of GIST biology, biomarkers, personalized cancer treatments, and provide a preclinical platform to evaluate new therapeutic agents for GIST

COVID-19 and hereditary spherocytosis: A recipe for hemolysis

We describe a patient infected with COVID-19 in the setting of a known chronic illness, HS, and the resulting presentation and medical complications

FGF19 Regulates Cell Proliferation, Glucose and Bile Acid Metabolism via FGFR4-Dependent and Independent Pathways

Fibroblast growth factor 19 (FGF19) is a hormone-like protein that regulates carbohydrate, lipid and bile acid metabolism. At supra-physiological doses, FGF19 also increases hepatocyte proliferation and induces hepatocellular carcinogenesis in mice. Much of FGF19 activity is attributed to the activation of the liver enriched FGF Receptor 4 (FGFR4), although FGF19 can activate other FGFRs in vitro in the presence of the coreceptor βKlotho (KLB). In this report, we investigate the role of FGFR4 in mediating FGF19 activity by using Fgfr4 deficient mice as well as a variant of FGF19 protein (FGF19v) which is specifically impaired in activating FGFR4. Our results demonstrate that FGFR4 activation mediates the induction of hepatocyte proliferation and the suppression of bile acid biosynthesis by FGF19, but is not essential for FGF19 to improve glucose and lipid metabolism in high fat diet fed mice as well as in leptin-deficient ob/ob mice. Thus, FGF19 acts through multiple receptor pathways to elicit pleiotropic effects in regulating nutrient metabolism and cell proliferation