A neutralizing leptin receptor antibody mitigates hypertrophy and hemodynamic dysfunction in the postinfarcted rat heart

The 16 kDa adipokine leptin has been shown to exert direct hypertrophic effects on cultured cardiomyocytes although its role as an endogenous contributor to postinfarction remodeling and heart failure has not been determined. We therefore investigated the effect of leptin receptor blockade in vivo on hemodynamic function and cardiac hypertrophy following coronary artery ligation (CAL). Cardiac function and biochemical parameters were measured in rats subjected to 7 or 28 days of left main CAL in the presence and absence of a leptin receptor antibody. Animals subjected to an identical treatment in which the artery was not tied served as sham-operated controls. CAL produced myocardial hypertrophy, which was most pronounced 28 days postinfarction as demonstrated by increases in both left ventricular weight-to-body weight ratio and atrial natriuretic peptide gene expression, both of which were abrogated by leptin receptor antagonism. Leptin receptor blockade also significantly improved left ventricular systolic function, attenuated the increased left ventricular end-diastolic pressure, and reduced the expression of genes associated with extracellular matrix remodeling 28 days following CAL. In conclusion, the ability of a leptin receptor-neutralizing antibody to improve cardiac function offers evidence that endogenous leptin contributes to cardiac hypertrophy following CAL. The possibility exists that targeting the myocardial leptin receptor represents a viable and novel approach toward attenuating postinfarction remodeling.     

Acute effects of capacitive and resistive electric transfer (CRet) on the Achilles tendon

This study aimed to investigate the acute effects of capacitive and resistive electric transfer (CRet) on Achilles tendon elongation during muscle contraction, as well as the circulation in the peritendinous region. Sixteen healthy men participated in this study. All 16 participants underwent 2 interventions: (1) CRet trial and (2) CRet without power (sham trial). Tendon elongation was measured four times. Using near-infrared spectroscopy, the blood circulation (volume of total-hemoglobin (Hb), oxygenated hemoglobin (oxy-Hb), and deoxygenated hemoglobin (deoxy-Hb)) was measured for 5 min before the intervention and for 30 min after the intervention. The differences between the measurements obtained before and after intervention were compared between the two interventions. The changes in tendon elongation and deoxy-Hb were not significantly different between the interventions. Total- and oxy-Hb were significantly increased in the CRet trial compared with the sham trial. In addition, the increases in total-Hb and oxy-Hb lasted for 30 min after the CRet intervention (CRet vs. sham: oxy-Hb: F = 8.063, p = 0.001, total-Hb: F = 4.564, p = 0.011). In conclusion, CRet significantly improved blood circulation in the peritendinous region.     

The ability of phosphodiesterase-5 inhibitors sildenafil and ordonafil to reverse L-NAME induced cardiac hypertrophy in the rabbit: possible role of calcineurin and p38

Phosphodiesterase 5 inhibitors (PDE-5Is) can suppress and (or) reverse pressure overload induced myocardial hypertrophy. This study investigated the suppressive effect of 2 PDE-5Is (sildenafil and ordonafil) on N-nitro-l-arginine methyl ester (L-NAME)-induced cardiac hypertrophy in rabbit heart, and examined their possible mechanism of action. L-NAME increased left ventricular thickness to 6.1± 0.18?mm from 4.6?± 0.13?mm (p?< 0.05), which regressed after treatment with either sildenafil or ordonafil to 5.1?± 0.1?mm and 4.8?± 0.2?mm, respectively (p?< 0.05). Phenylephrine increased neonatal rat ventricular myocyte cell surface area to 131%?± 3% of the control value, which was associated with significant increment in ERK1/2 to 143%?± 5% of the control value (p?< 0.05). Ordonafil and sildenafil decreased cell surface area to 95%?± 3% and 90%?± 1% of the control value, respectively. Both drugs decreased ERK1/2 to 88%?± 4% of the control value. Calcineurin activity was significantly decreased after 1?h of treatment with 0.1?mg·L(-1) ordonafil (1.15?± 0.05, p?< 0.05). For sildenafil (0.1?mg·L(-1)), calcineurin activity significantly decreased only after 24?h of incubation (22%). Also p38 activation was attenuated by ordonafil and sildenafil (0.1?mg·L(-1)). It is suggested that both drugs have the ability to reverse L-NAME-induced cardiac hypertrophy and suppress phenylphrine-induced myocyte hypertrophy, and that these effects may be mediated through the attenuation of calcineurin and its downstream signaling pathways (p38) in neonatal rat ventricular myocytes.     

Interaction of spin-labeled tryptophan with sickle hemoglobin: probing the microenvironment of the contact sites by spin-probe--spin-label techniques

The spin-labeled tryptophan was used as a structural probe of hemoglobin contact sites. The ESR spectral data indicated that the probe exhibits weak binding to hemoglobin with a dissociation constant of 3.2.10(-5) and 4.0 mol bound per hemoglobin tetramer. The spectrum suggested that the bound tryptophan was 'partially immobilized' with a correlation time reflecting the environment of the tryptophan binding site of 8.2 ns. The topology of the contact sites was investigated by using dual spin-label methodology in which spin-labeled tryptophan and (2H,15N) substituted and deuterated maleimide spin label [2H-15N]MSL covalently-bound to Cys-beta 93 residue were used. The ESR spectral data suggested that the tryptophan binding sites were located within 8-10 A of the nitroxide free radical of spin-labeled hemoglobin. The environment of the contact sites is discussed.     

Stable coexistence of two <Emphasis Type="Italic">Caldicellulosiruptor</Emphasis> species in a <Emphasis Type="Italic">de novo</Emphasis> constructed hydrogen-producing co-culture

Background  

Mixed culture enrichments have been used frequently for biohydrogen production from different feedstock. In spite of the several advantages offered by those cultures, they suffer poor H₂ yield. Constructing defined co-cultures of known H₂ producers may offer a better performance than mixed-population enrichments, while overcoming some of the limitations of pure cultures based on synergies among the microorganisms involved.     

ROS Dynamics Delineate Functional States of Hippocampal Neural Stem Cells and Link to Their Activity-Dependent Exit from Quiescence

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Glycolysis regulates Hedgehog signalling via the plasma membrane potential

The authors regret omitting the citation of a bioRxiv preprint study by preprint: Emmons‐Bell et al (2020), who independently discovered the role of ion channel‐dependent membrane depolarization for Smo membrane accumulation in the fly wing disc. This study used a different methodological approach and did not describe the mechanism of how membrane potential affects hedgehog signaling. The reference is herewith added.