Characterization and quantitation of the circulating forms of serum transferrin receptor using domain-specific antibodies

To characterize the nature of the immunoreactive transferrin receptor in human serum, antisera were developed to peptide sequences of the extracellular domain of human transferrin receptor between amino acids 107 and 120 and the intracellular domain between amino acids 40 and 54. Antisera against the extracellular domain exhibited reactivity against both purified intact receptor and immunopurified circulating receptor, whereas antisera against the intracellular domain reacted only with intact receptor. Using competitive binding enzyme-linked immunosorbent assays, transferrin receptor in ultracentrifuged sera from normal subjects and patients with sickle cell anemia could be detected with antisera against the extracellular but not the intracellular domain. When the pellet obtained by ultracentrifugation of these sera was assayed after solubilization in 1% teric (polyoxyethylene-9-lauryl ether), only 0.6% of total serum receptor was detected in normal subjects and 3.8% in subjects with sickle cell disease. Roughly equal amounts of this pelleted immunoactivity were detected with antibodies against the extracellular and intracellular domains. These results indicate that less than 1% of transferrin receptor in normal human sera is intact receptor consistent with an exosomal origin and that virtually all circulating transferrin receptor is in the form of a truncated extracellular domain.     

The effects of exergames on anxiety levels: A systematic review and meta-analysis

There are currently many different approaches to performing exergames and there is still no consensus as to whether exergames are able to reduce anxiety levels, as well as whether exergames provide greater reductions on anxiety levels when added to traditional forms of clinical interventions. Therefore, the aim of the present systematic review and meta-analysis was to access data from studies that evaluated the effects of exergames on anxiety levels in humans. PubMed, Scopus and Cochrane databases were searched up to 22 February 2019. Inclusion criteria were acute and chronic (short-term and long-term interventions) studies which evaluated the effects of exergames in anxiety levels as primary or secondary aim. Of the 1342 studies found, 17 and 10 were included in qualitative analyses and meta-analyses, respectively. The within-group analysis found that exergames (standardized mean difference [SMD]: −0.57 [95% Confidence interval (CI): −0.86 to −0.28], P < .001) and usual care (SMD: −0.21 [95% CI: −0.34 to −0.08], P = .002) resulted in significant improvements on anxiety levels. However, the between-group meta-analysis on the effects of control interventions vs exergames (SMD: 0.02 [95% CI: −0.55 to 0.60], P = .939) found no significant difference between groups in anxiety levels reductions. There was also no significant difference (SMD: −0.04 [95% CI: −0.32 to 0.25], P = .805) between usual care vs exergames plus usual care interventions in anxiety levels reductions. Although exergames demonstrated within-group improvements in anxiety levels across different clinical populations, it was not greater than the effects from non-exercise interventions. Also, given the paucity of studies, small sample sizes, different research designs, and different population investigated, the existing evidence is insufficient to support the advantages of usual care supplemented by exergame intervention over usual care standalone in anxiety levels reduction.     

Effects of metabolic inhibition on cytoplasmic calcium and contraction in smooth muscle of rat portal vein

Contractions in the rat portal vein, evoked by spontaneous action potentials or depolarizing high-K⁺ solution, are rapidly and reversibly inhibited by hypoxia or respiratory blockade. Intracellular free calcium ([Ca²⁺]_i) was measured using Fura-2 to evaluate the effects of metabolic blockade on excitation–contraction coupling. Spontaneous contractions were associated with transient increases in [Ca²⁺]_i. During exposure to cyanide (0.2–0.4 mm ) or 2,4-dinitrophenol (30 μm ) the duration and amplitude of the Ca²⁺ transients were decreased, leading to a decreased mean time integral of the individual [Ca²⁺]_i transient, and corresponding decrease in the duration and amplitude of the contraction. Basal [Ca²⁺]_i was increased in the presence of the metabolic inhibitors. High-K⁺ (40 mM) contractions caused a sustained increase in [Ca²⁺]_i, which was not inhibited by exposure to cyanide, although the amplitude of the associated contraction was greatly reduced. Together with the earlier demonstration of decreased 20 kD myosin light chain phosphorylation under these conditions, this indicates that the activation of contraction is influenced by metabolism via the energy dependence of the light chain phosphorylation reaction. Thus at least three steps in the excitation–contraction sequence are influenced by inhibition of oxidative metabolism: membrane excitation, light chain phosphorylation, and the cross-bridge cycle. This provides mechanisms for a high degree of metabolic sensitivity of vascular tone, of importance for the adaptation of blood flow to tissue metabolic demands.