Cardiovascular responses to light isometric and aerobic exercise in 21- and 59-year-old males

The effects of aging on the cardiovascular response to continuous light isometric and aerobic exercise remains to be determined. Thus, the purpose of this study was to compare the cardiovascular response of young and older males during light handgrip and cycle ergometry exercise. Blood pressure, heart rate, rate pressure product, as well as pre-ejection period (derived from impedance cardiography) were obtained for 15 young [mean (SE) age: 21 (0.7) years] and 15 older males [59 (0.8) years] during and after light handgrip exercise and cycle ergometry. The parasympathetic influence on the heart was also assessed through a time-series analysis of heart period variability (HPVts). Both during and when recovering from the handgrip exercise and cycle ergometry, the older subjects exhibited a significantly higher absolute systolic and diastolic blood pressure, and rate pressure product, and a lower HRVts than the young subjects. Relative to baseline, the change in pre-ejection period was lower for the young subjects during the handgrip and cycle ergometry, tasks. These results indicate that although the sympathetic influence on both the myocardium and the vasculature was less pronounced in the older males, the aging cardiovasculature was under greater hemodynamic stress both during rest and during exposure to light isometric and aerobic challenge.     

Evaluation of a structured treatment discontinuation in patients with inoperable alveolar echinococcosis on long-term benzimidazole therapy: A retrospective cohort study

ObjectivesAlveolar echinococcosis (AE) is an orphan zoonosis of increasing concern in endemic areas, including Europe. It frequently presents in an advanced, inoperable stage, that requires life-long parasitostatic benzimidazole therapy. In some patients, long-term therapy leads to negative anti-Em18 antibody ELISA and PET. It is disputed, whether these patients are truly cured and treatment can be safely discontinued. Our aim was to retrospectively assess long-term outcome of 34 patients with inoperable AE who participated in a previous study to determine feasibility of benzimidazole treatment cessation.MethodsRetrospective analysis of medical charts was undertaken in all 34 AE patients who participated in our previous study. Of particular interest were AE recurrence or other reasons for re-treatment in patients who stopped benzimidazole therapy and whether baseline clinical and laboratory parameters help identify of patients that might qualifiy for treatment cessation. Additionally, volumetric measurement of AE lesions on contrast-enhanced cross-sectional imaging was performed at baseline and last follow-up in order to quantify treatment response.Results12 of 34 patients stopped benzimidazole therapy for a median of 131 months. 11 of these patients showed stable or regressive AE lesions as determined by volumetric measurement. One patient developed progressive lesions with persistently negative anti-Em18 antibody ELISA but slight FDG-uptake in repeated PET imaging. At baseline, patients who met criteria for treatment cessation demonstrated higher lymphocyte count and lower total IgE.ConclusionTreatment cessation is feasible in inoperable AE patients, who demonstrate negative anti-Em18 antibody ELISA and PET on follow-up. Close monitoring including sectional imaging is strongly advised.     

When things get MESI: The Manipulation Experiments Synthesis Initiative—A coordinated effort to synthesize terrestrial global change experiments

Responses of the terrestrial biosphere to rapidly changing environmental conditions are a major source of uncertainty in climate projections. In an effort to reduce this uncertainty, a wide range of global change experiments have been conducted that mimic future conditions in terrestrial ecosystems, manipulating CO₂, temperature, and nutrient and water availability. Syntheses of results across experiments provide a more general sense of ecosystem responses to global change, and help to discern the influence of background conditions such as climate and vegetation type in determining global change responses. Several independent syntheses of published data have yielded distinct databases for specific objectives. Such parallel, uncoordinated initiatives carry the risk of producing redundant data collection efforts and have led to contrasting outcomes without clarifying the underlying reason for divergence. These problems could be avoided by creating a publicly available, updatable, curated database. Here, we report on a global effort to collect and curate 57,089 treatment responses across 3644 manipulation experiments at 1145 sites, simulating elevated CO₂, warming, nutrient addition, and precipitation changes. In the resulting Manipulation Experiments Synthesis Initiative (MESI) database, effects of experimental global change drivers on carbon and nutrient cycles are included, as well as ancillary data such as background climate, vegetation type, treatment magnitude, duration, and, unique to our database, measured soil properties. Our analysis of the database indicates that most experiments are short term (one or few growing seasons), conducted in the USA, Europe, or China, and that the most abundantly reported variable is aboveground biomass. We provide the most comprehensive multifactor global change database to date, enabling the research community to tackle open research questions, vital to global policymaking. The MESI database, freely accessible at doi.org/10.5281/zenodo.7153253 , opens new avenues for model evaluation and synthesis-based understanding of how global change affects terrestrial biomes. We welcome contributions to the database on GitHub.     

Morphogenesis and cellular proliferation pattern in the developing antennal lobe of Drosophila melanogaster

The adult antennal lobe of Drosophila melanogaster emerges from a precursor, the larval antennal lobe. Pulse and pulse-chase labelling of dividing cells in larvae and pupae with bromodeoxyuridine confirmed previous data that some of the interneurons of the adult antennal lobe derive from a lateral neuroblast which starts to divide early in the first larval instar. However, the majority of these interneurons originate from neuroblasts that initiate mitosis at later stages, with a peak of about 10–12 pairs of dividing neuroblasts in the late third larval instar. No clustering of adult antennal lobe neurons according to their birthdates was observed. In contrast to neurons, terminal divisions of glia in the antennal lobe reach their maximum only 12 h after puparium formation.     

Genetically displaced sensory neurons in the head of Drosophila project via different pathways into the same specific brain regions

The sensory projection pattern of homoeotic antennal or leg tissue in the proboscis of the mutant proboscipedia in Drosophila melanogaster was studied using orthograde diffusion of cobalt chloride. Both kinds of ectopic nerve fibers terminate in the normal center of the proboscis and in the antennal glomerulus of the brain. These centers are attained by axons which may pass via four different peripheral nerves. In contrast, wild-type proboscis fibers use only one pathway. Depending on the site of entrance into the brain, homoeotic axons may project into the proboscis center first, and then into the antennal glomerulus, or vice versa. Consequently, the tract between these two brain regions may be followed in opposite directions. Ectopic leg axons extending into normal leg centers in the thoracic ganglion have not been found. Projection patterns in proboscipedia are discussed together with those of the leg-like antenna in spineless-aristapedia (R. F. Stocker and P. A. Lawrene, 1981, Dev. Biol.82, 224–237). The fact that displaced antennal and leg neurons project specifically into normal proboscis and antennal centers may reflect the serial homology of antennal, leg, and proboscis neurons, and similar homology of the corresponding centers.     

Some group N plasmids makeEscherichia coli K-12 strain AB1157 dependent on exogenous purine

Escherichia coli K-12 strain AB1157 given the conjugative group N plasmid R46 (or its derivative, pKM101, or plasmid R384N) grew only very slowly on defined medium containing the known growth-factor requirements of AB1157, which do not include any purine. Addition of adenine or hypoxanthine (or their nucleosides) restored normal growth; guanine and xanthine (and their nucleosides) were ineffective, because of thegpt defect caused by deletionproA2. Variants of AB1157(R46) able to grow rapidly on defined medium without purine were tetracycline-sensitive and/or transfer-defective; an, R46 gene,slo, causing purine auxotrophy, is inferred to be betweentet andtra.     

Oxidation of 3-hydroxyanthranilic acid to the phenoxazinone cinnabarinic acid by peroxyl radicals and by compound I of peroxidases or catalase.

Since 3-hydroxyanthranilic acid (3HAA), an oxidation product of tryptophan metabolism, is a powerful radical scavenger [Christen, S., Peterhans, E., & Stocker, R. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 2506], its reaction with peroxyl radicals was investigated further. Exposure to aqueous peroxyl radicals generated at constant rate under air from the thermolabile radical initiator 2,2'-azobis[2-amid-inopropane] hydrochloride (AAPH) resulted in rapid consumption of 3HAA with initial accumulation of its cyclic dimer, cinnabarinic acid (CA). The initial rate of formation of the phenoxazinone CA accounted for approximately 75% of the initial rate of oxidation of 3HAA, taking into account that 2 mol of 3HAA are required to form 1 mol of CA. Consumption of 3HAA under anaerobic conditions (where alkyl radicals are produced from AAPH) was considerably slower and did not result in detectable formation of CA. Addition of superoxide dismutase enhanced autoxidation of 3HAA as well as the initial rates of peroxyl radical-induced oxidation of 3HAA and formation of CA by approximately 40-50%, whereas inclusion of xanthine/xanthine oxidase decreased the rate of oxidation of 3HAA by approximately 50% and inhibited formation of CA almost completely, suggesting that superoxide anion radical (O2.-) was formed and reacted with reaction intermediate(s) to curtail formation of CA. Formation of CA was also observed when 3HAA was added to performed compound I of horseradish peroxidase (HRPO) or catalytic amounts of either HRPO, myeloperoxidase, or bovine liver catalase together with glucose/glucose oxidase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cloning and expression of a human voltage-gated potassium channel. A novel member of the RCK potassium channel family.

We have isolated and characterized a human cDNA (HBK2) that is homologous to novel member (RCK2) of the K+ channel RCK gene family expressed in rat brain. RCK2 mRNA was detected predominantly in midbrain areas and brainstem. The primary sequences of the HBK2/RCK2 K+ channel proteins exhibit major differences to other members of the RCK gene family. The bend region between segments S1 and S2 is unusually long and does not contain the N-glycosylation site commonly found in this region. They might be O-glycosylated instead. Functional characterization of the HBK2/RCK2 K+ channels in Xenopus laevis oocytes following micro-injection in in vitro transcribed HBK2 or RCK2 cRNA showed that the HBK2/RCK2 proteins form voltage-gated K+ channels with novel functional and pharmacological properties. These channels are different to RCK1, RCK3, RCK4 and RCK5 K+ channels.     

Segment IV of a Salmonella flagellin gene specifies flagellar antigen epitopes

Each of the two mutants isolated from a fliC (= hag, flagellin-deficient) Escherichia coli strain made motile by a plasmid carrying the fliC gene of Salmonella muenchen by selection for motility in the presence of anti-d (Salmonella flagellar antigen) serum had both lost and gained one or more subfactors of the wild-type antigen. In one mutant codon 246 was GAC (alanine) instead of GCC (asparagine); the other had a deletion of 105 base pairs, explicable by a 10bp direct repeat, starting at bases 782 and 887. The in vitro removal of a 48bp EcoRV(631)/EcoRV(679) fragment produced plasmid pLS408, which was found to lack a subfactor of wild-type antigen d but able to confer motility on flagellin-negative Salmonella sp. (and used for insertion of epitope-specifying oligonucleotides at its EcoRV site). Immunoblotting with absorbed and unabsorbed sera from rabbits immunized with E. coli with wild-type or mutated antigen d showed that the fusion proteins specified by lambda gt11 with the N-terminal part of gene lacZ joined to a restriction fragment coding for residues 145-391 of flagellin gave the same pattern of parent-specific and mutant-specific reactions as the flagellate bacteria. Four out of five similarly selected mutants had the same 105 bp deletion as the first-isolated mutant; the fifth had a 72 bp deletion made possible by a 7-base pair direct repeat, starting at positions 649 and 721. All these changes in serological character without loss of function affected segment IV, specifying residues 182 to 308 of the total of 505, where there is little homology between different flagellar-antigen alleles.