Metabolite-mediated catalyst conversion of PFK and PFP

Metabolites known to occur in the cytosol of photosynthetic leaf cells were found to mediate the reversible conversion of pyrophosphate—D-fructose-6-phosphate 1-phosphotransferase (PFP) to phosphofructokinase (PFK) in partially purified preparations from spinach leaves. Preincubation of PFP with fructose 2,6-bisphosphate, ATP or fructose 6-phosphate converted PFP to PFK. The reverse reaction (PFK → PFP) was promoted by UDP-glucose plus pyrophosphate. These conversions in catalytic capability were accompanied by changes in molecular mass and charge. The results are in accord with the view that the alterations in PFP and PFK activity, provisionally called ‘metabolite-mediated catalyst conversion’, represent a regulatory mechanism to direct left cytosolic carbon flux in either the biosynthetic or degradatory direction

River-Based Surveys for Assessing Riparian Bird Populations: Cerulean Warbler as a Test Case

This is the published version. Copyright Eagle Hill InstituteBirds concentrated in riparian habitats are poorly sampled by traditional survey methods because of the difficulties associated with accessing these habitats. Our objectives were to test the effectiveness of river-based surveys to determine the status, distribution, and relative abundance for riparian bird species in Missouri and northern Arkansas, with special emphasis on Dendroica cerulea (Cerulean Warbler). Our canoe-based surveys revealed an average of 2.3 and 0.8 singing male Cerulean Warblers/river km along the Current River (128 river km surveyed), MO, and the Buffalo National River (96 river km), AR. Nonparametric estimates for repeated surveys of the same river stretches indicate that 69–79% of singing male Cerulean Warblers were detected. However, the bias associated with the estimate methodology and independent song rate data suggest those are conservative estimates. In comparison with land-based point-counts, this river-based protocol offers a quick and efficient assessment of Cerulean Warblers in riparian areas

Extinction Curves, Distances, and Clumpiness of Diffuse Interstellar Dust Clouds

We present CCD photometry in UBVRI of several thousand Galactic field stars in four large (>1 degree^2) regions centered on diffuse interstellar dust clouds, commonly referred to as ``cirrus'' clouds (with optical depth A_V less than unity). Our goal in studying these stars is to investigate the properties of the cirrus clouds. A comparison of the observed stellar surface density between on-cloud and off-cloud regions as a function of apparent magnitude in each of the five bands effectively yields a measure of the extinction through each cloud. For two of the cirrus clouds, this method is used to derive UBVRI star counts-based extinction curves, and U-band counts are used to place constraints on the cloud distance. The color distribution of stars and their location in (U-B, B-V) and (B-V, V-I) color-color space are analyzed in order to determine the amount of selective extinction (reddening) caused by the cirrus. The color excesses, A_lambda-A_V, derived from stellar color histogram offsets for the four clouds, are better fit by a reddening law that rises steeply towards short wavelengths [R_V==A_V/E(B-V)<=2] than by the standard law (R_V=3.1). This may be indicative of a higher-than-average abundance of small dust grains relative to larger grains in diffuse cirrus clouds. The shape of the counts-based effective extinction curve and a comparison of different estimates of the dust optical depth (extinction optical depth derived from background star counts/colors; emission optical depth derived from far infrared measurements), are used to measure the degree of clumpiness in clouds. The set of techniques explored in this paper can be readily adapted to the Sloan Digital Sky Survey data set in order to carry out a systematic, large-scale study of cirrus clouds.Comment: 22 pages, 13 figures (postscript, gif, jpg). Accepted for publication in the Astronomical Journal, scheduled for the May 1999 issue. Full resolution postscript versions of all figures are available at http://www.ucolick.org/~arpad

SandflyMap: leveraging spatial data on sand fly vector distribution for disease risk assessments

We feature SandflyMap (www.sandflymap.org), a new map service within VectorMap (www.vectormap.org) that allows free public online access to global sand fly, tick and mosquito collection records and habitat suitability models. Given the short home range of sand flies, combining remote sensing and collection point data give a powerful insight into the environmental determinants of sand fly distribution. SandflyMap is aimed at medical entomologists, vector disease control workers, public health officials and health planners. Data are checked for geographical and taxonomic errors, and are comprised of vouchered specimen information, and both published and unpublished observation data. SandflyMap uses Microsoft Silverlight and ESRI’s ArcGIS Server 10 software platform to present disease vector data and relevant remote sensing layers in an online geographical information system format. Users can view the locations of past vector collections and the results of models that predict the geographic extent of individual species. Collection records are searchable and downloadable, and Excel collection forms with drop down lists, and Excel charts to country, are available for data contributors to map and quality control their data. SandflyMap makes accessible, and adds value to, the results of past sand fly collecting efforts. We detail the workflow for entering occurrence data from the literature to SandflyMap, using an example for sand flies from South America. We discuss the utility of SandflyMap as a focal point to increase collaboration and to explore the nexus between geography and vector-borne disease transmission

CIViCpy: A Python software evelopment and analysis toolkit for the CIViC knowledgebase

PURPOSE: Precision oncology depends on the matching of tumor variants to relevant knowledge describing the clinical significance of those variants. We recently developed the Clinical Interpretations for Variants in Cancer (CIViC; civicdb.org) crowd-sourced, expert-moderated, and open-access knowledgebase. CIViC provides a structured framework for evaluating genomic variants of various types (eg, fusions, single-nucleotide variants) for their therapeutic, prognostic, predisposing, diagnostic, or functional utility. CIViC has a documented application programming interface for accessing CIViC records: assertions, evidence, variants, and genes. Third-party tools that analyze or access the contents of this knowledgebase programmatically must leverage this application programming interface, often reimplementing redundant functionality in the pursuit of common analysis tasks that are beyond the scope of the CIViC Web application. METHODS: To address this limitation, we developed CIViCpy (civicpy.org), a software development kit for extracting and analyzing the contents of the CIViC knowledgebase. CIViCpy enables users to query CIViC content as dynamic objects in Python. We assess the viability of CIViCpy as a tool for advancing individualized patient care by using it to systematically match CIViC evidence to observed variants in patient cancer samples. RESULTS: We used CIViCpy to evaluate variants from 59,437 sequenced tumors of the American Association for Cancer Research Project GENIE data set. We demonstrate that CIViCpy enables annotation of \u3e 1,200 variants per second, resulting in precise variant matches to CIViC level A (professional guideline) or B (clinical trial) evidence for 38.6% of tumors. CONCLUSION: The clinical interpretation of genomic variants in cancers requires high-throughput tools for interoperability and analysis of variant interpretation knowledge. These needs are met by CIViCpy, a software development kit for downstream applications and rapid analysis. CIViCpy is fully documented, open-source, and available free online

Assessment of computed tomography simulators used in radiotherapy treatment planning in Serbia, Croatia, and Bosnia and Herzegovina

The purpose of this work was to evaluate computed tomography simulators used in radio-therapy treatment planning in Serbia, Croatia, and Bosnia and Herzegovina. A survey of quality assurance programmes of 24 computed tomography simulators in 16 facilities was conducted. A dedicated CT-to-ED phantom was scanned at 120 kV and 140 kV, to obtain CT-to-ED conversion curves as well as CTDIvol. Thoracal phantoms were scanned in the standard and extended field of view to evaluate the dosimetric effect on treatment planning and delivery. The mean age of the measured scanners was 5.5 years. The mean water HU value was –6.5 (all scanners, all voltages) and air HU value was –997. Extended field of view computed tomography data differ from the standard field of view and differences between conversion curves have significant dosimetric impact. The CTDI data showed a large range of values between centers. Better quality assurance of computed tomography simulators in all countries is recommended. The CT-to-ED curve could be used as default at one voltage and per manufacturer. Extended field of view imaging can be used, but treatment planning should be avoided in the regions out of the standard field of view

Fast- or Slow-inactivated State Preference of Na+ Channel Inhibitors: A Simulation and Experimental Study

Sodium channels are one of the most intensively studied drug targets. Sodium channel inhibitors (e.g., local anesthetics, anticonvulsants, antiarrhythmics and analgesics) exert their effect by stabilizing an inactivated conformation of the channels. Besides the fast-inactivated conformation, sodium channels have several distinct slow-inactivated conformational states. Stabilization of a slow-inactivated state has been proposed to be advantageous for certain therapeutic applications. Special voltage protocols are used to evoke slow inactivation of sodium channels. It is assumed that efficacy of a drug in these protocols indicates slow-inactivated state preference. We tested this assumption in simulations using four prototypical drug inhibitory mechanisms (fast or slow-inactivated state preference, with either fast or slow binding kinetics) and a kinetic model for sodium channels. Unexpectedly, we found that efficacy in these protocols (e.g., a shift of the “steady-state slow inactivation curve”), was not a reliable indicator of slow-inactivated state preference. Slowly associating fast-inactivated state-preferring drugs were indistinguishable from slow-inactivated state-preferring drugs. On the other hand, fast- and slow-inactivated state-preferring drugs tended to preferentially affect onset and recovery, respectively. The robustness of these observations was verified: i) by performing a Monte Carlo study on the effects of randomly modifying model parameters, ii) by testing the same drugs in a fundamentally different model and iii) by an analysis of the effect of systematically changing drug-specific parameters. In patch clamp electrophysiology experiments we tested five sodium channel inhibitor drugs on native sodium channels of cultured hippocampal neurons. For lidocaine, phenytoin and carbamazepine our data indicate a preference for the fast-inactivated state, while the results for fluoxetine and desipramine are inconclusive. We suggest that conclusions based on voltage protocols that are used to detect slow-inactivated state preference are unreliable and should be re-evaluated

Gender Difference in the Effects of COVID-19 Pandemic on Mechanical Reperfusion and 30-Day Mortality for STEMI: Results of the ISACS-STEMI COVID-19 Registry

Background. Several reports have demonstrated the impact of the COVID-19 pandemic on the management and outcome of patients with ST-segment elevation myocardial infarction (STEMI). The aim of the current analysis is to investigate the potential gender difference in the effects of the COVID-19 pandemic on mechanical reperfusion and 30-day mortality for STEMI patients within the ISACS-STEMI COVID-19 Registry. Methods. This retrospective multicenter registry was performed in high-volume primary percutaneous coronary intervention (PPCI) centers on four continents and included STEMI patients undergoing PPCIs in March–June 2019 and 2020. Patients were divided according to gender. The main outcomes were the incidence and timing of the PPCI, (ischemia time ≥ 12 h and door-to-balloon ≥ 30 min) and in-hospital or 30-day mortality. Results. We included 16683 STEMI patients undergoing PPCIs in 109 centers. In 2020 during the pandemic, there was a significant reduction in PPCIs compared to 2019 (IRR 0.843 (95% CI: 0.825–0.861, p < 0.0001). We did not find a significant gender difference in the effects of the COVID-19 pandemic on the numbers of STEMI patients, which were similarly reduced from 2019 to 2020 in both groups, or in the mortality rates. Compared to prepandemia, 30-day mortality was significantly higher during the pandemic period among female (12.1% vs. 8.7%; adjusted HR [95% CI] = 1.66 [1.31–2.11], p < 0.001) but not male patients (5.8% vs. 6.7%; adjusted HR [95% CI] = 1.14 [0.96–1.34], p = 0.12). Conclusions. The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a 16% reduction in PPCI procedures similarly observed in both genders. Furthermore, we observed significantly increased in-hospital and 30-day mortality rates during the pandemic only among females. Trial registration number: NCT 04412655