Mass distributions of a macromolecular assembly based on electrospray ionization mass spectrometric masses of the constituent subunits

Macromolecular assemblies containing multiple protein subunits and having masses in the megadalton (MDa) range are involved in most of the functions of a living cell. Because of variation in the number and masses of subunits, macromolecular assemblies do not have a unique mass, but rather a mass distribution. The giant extracelular erythrocruorins (Ers), ∼ 3.5 MDa, comprized of at least 180 polypeptide chains, are one of the best characterized assemblies. Three-dimensional reconstructions from cryoelectron microscopic images show them to be hexagonal bilayer complexes of 12 subassemblies, each comprised of 12 globin chains, anchored to a subassembly of 36 nonglobin linker chains. We have calculated the most probable mass distributions forLumbricus andRiftia assemblies and their globin and linker subassemblies, based on theLumbricus Er stoichiometry and using accurate subunit masses obtained by electrospray ionization mass spectrometry. The expected masses ofLumbricus andRiftia Ers are 3.517 MDa and 3.284 MDa, respectively, with a possible variation of ∼ 9% due to the breadth of the mass distributions. TheLumbricus Er mass is in astonishingly good agreement with the mean of 23 known masses, 3.524 ± 0.481 MDa.     

Cellular remodeling in heart failure disrupts K(ATP) channel-dependent stress tolerance

ATP-sensitive potassium (K(ATP)) channels are required for maintenance of homeostasis during the metabolically demanding adaptive response to stress. However, in disease, the effect of cellular remodeling on K(ATP) channel behavior and associated tolerance to metabolic insult is unknown. Here, transgenic expression of tumor necrosis factor alpha induced heart failure with typical cardiac structural and energetic alterations. In this paradigm of disease remodeling, K(ATP) channels responded aberrantly to metabolic signals despite intact intrinsic channel properties, implicating defects proximal to the channel. Indeed, cardiomyocytes from failing hearts exhibited mitochondrial and creatine kinase deficits, and thus a reduced potential for metabolic signal generation and transmission. Consequently, K(ATP) channels failed to properly translate cellular distress under metabolic challenge into a protective membrane response. Failing hearts were excessively vulnerable to metabolic insult, demonstrating cardiomyocyte calcium loading and myofibrillar contraction banding, with tolerance improved by K(ATP) channel openers. Thus, disease-induced K(ATP) channel metabolic dysregulation is a contributor to the pathobiology of heart failure, illustrating a mechanism for acquired channelopathy.     

Contents Volume 26 (2000)

Volume Contents

Contents Volume 26 (2000)     

Mutants ofPhycomyceswith Decreased Gallic Acid Content

Weinkove, D., Poyatos, J. A., Greiner, H., Oltra, E., Avalos, J., Fukshansky, L., Barrero, A. F., and Cerdá-Olmedo, E. 1998. Mutants ofPhycomyceswith decreased gallic acid content.Fungal Genetics and Biology25, 196–203. Most plants and some fungi accumulate phenols. Two hydroxybenzoic acids, gallic and protocatechuic acids, are abundant in the giant sporangiophores of the zygomycetePhycomyces blakesleeanus,much more so than in the basal mycelium or the culture medium. The actual concentrations vary with illumination, age of the culture, and composition of the medium. We devised a simple screening procedure to isolatehbamutants whose sporangiophores contained less gallic acid than the wild type. The most useful mutant had very low concentrations of hydroxybenzoic acids in the sporangiophores, but about the same as the wild type in the basal mycelium and the medium. The mutant was only slightly different from the wild type in growth and morphology. Mutant and wild-type sporangiophores grew away from ultraviolet C sources (260 nm) equally well. Contrary to previous conjectures, ultraviolet tropism does not depend on the ultraviolet absorption of gallic acid or other free hydroxybenzoic acids in the sporangiophore. Against expectations, phenols did not impair DNA extraction: sporangiophores produced better DNA preparations than basal mycelia and thehbamutant only slightly better than the wild type.     

Epidemiology of venous thromboembolism (VTE) associated with pregnancy

This review is focused on the epidemiology of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), associated with pregnancy. Superficial vein thrombosis, a less hazardous and less studied type of thrombosis in pregnant women, is beyond the scope of this review. This study discusses the VTE incidence rate in women from developed countries for both antepartum and postpartum periods and for subpopulations of women affected by additional risk factors, such as thrombophilias, circulatory diseases, preeclampsia of varying degrees of severity, and Caesarean section. To minimize bias due to historical changes in medical and obstetric practices, lifestyle, diet, etc., this review is generally limited to relatively recent studies, i.e., those that cover the last 35 years. The absolute risk or incidence rate was used to ascertain risk of VTE associated with pregnancy. For the studies where the direct incidence rates of VTE were not reported, we calculated an estimate of the observed but not reported absolute incidence rates using the data presented in respective articles. Birth Defects Research (Part C) 105:167–184, 2015. © 2015 Wiley Periodicals, Inc.     

Stereotactic body radiation therapy (SBRT) of adrenal gland metastases in oligometastatic and oligoprogressive disease

BackgroundStereotactic body radiation therapy (SBRT) as a form of noninvasive treatment that is becoming increasingly used to manage cancers with adrenal gland metastases. There is a paucity of data on safety and efficacy of this modality. The aim of the study was to evaluate the safety and efficacy of adrenal gland SBRT in oligometastatic and oligoprogressive disease.Materials and methodsIn this retrospective study, we performed a single-institution analysis of 26 adrenal lesions from 23 patients with oligometastatic or oligoprogressive disease treated from 2013 to 2019 with the goal of achieving durable local control. Palliative cases were excluded. Radiation dosimetry data was collected. Kaplan Meier product estimator and Cox proportional hazards regression analysis were used for statistical analysis.ResultsThe median dose was 36 Gy in 3 fractions (range: 24–50 Gy and 3–6 fractions) with a median biologically effective dose (BED10) of 72 (range: 40–100). 1-year local control rate was 80% and median local control was not achieved due to a low number of failures. 1- and 2-year overall survival rates were 66% and 32%. Toxicity was mild with only one case of grade 2 nausea and no grade 3–5 toxicity. Higher neutrophil to lymphocyte ratio was associated with worse overall survival and a trend toward worse progression-free survival. In addition, worse performance status and lower BED10 were associated with worse survival. No such association could be shown for primary tumor location, histology, size or stage.ConclusionAdrenal SBRT for oligometastatic or oligoprogressive disease is a safe and effective form of treatment.     

The interaction of light irradiance with ethylene in regulating growth of Helianthus annuus shoot tissues

Shade light found in ecological niches where plants are growing under a canopy or in proximity of taller neighbouring vegetation consist mainly of two separate light signals: low red to far-red ratio and low photosynthetically active radiation (PAR). The effect of the latter on the growth of 7-day old sunflower shoots was examined by assessing hypocotyl, cotyledon and leaf tissue growth under three varying PAR levels: near-normal of 1,000 μmol m^?2 s^?1, low of 100 μmol m^?2 s^?1 and very low of 10 μmol m^?2 s^?1. Then, the possible interaction between PAR signaling and ethylene in regulating growth of these sunflower tissues was investigated. The results showed that gradual decrease in PAR level increases hypocotyl elongation and decreases ethylene evolution. However, gradual decrease in PAR level decreases cotyledon and leaf growth and increases ethylene evolution. Thus it seems possible that PAR regulation of shoot growth is mediated by changes in ethylene evolution in tissue specific manner. This hypothesis was supported by experiments with the ethylene releasing factor, ethephon, and the ethylene biosynthesis inhibitor, AVG, as well as by transfer experiments where sunflower seedlings were transferred from one PAR regime to another with subsequent growth and ethylene measurements.