Elementary steps in protein folding.

The mechanism of protein folding is under intense theoretical and experimental investigation. From stopped-flow mixing experiments we have detailed knowledge of processes slower than about 1 ms, but until recently little was known about folding and unfolding reactions on the microsecond to nanosecond time scale. The use of novel techniques allowed to explore the elementary steps in protein folding, such as intrachain diffusion and formation of alpha-helices, beta-hairpins and loop structures. This brief review discusses the time scales of these early elementary events which are crucial for the understanding of how proteins fold.     

Direct microsensor measurement of nitric oxide production by the osteoclast.

Nitric oxide (NO) triggers marked osteoclast retraction which closely resembles that due to Ca2+. The effect of Ca2+ has been attributed to a stimulated release of NO. Here, we show for the first time, by direct measurement with a microsensor, that osteoclasts do indeed produce NO and that this production is enhanced by a high Ca2+. We also show that the Ca2+ ionophore, A23187, mimics the latter. Furthermore, osteoclasts on dentine produce more NO than osteoclasts on glass and NO release from dentine-plated osteoclasts is much less sensitive to stimulation by Ca2+. Finally, the microsomal Ca2+ store-depleting agent, thapsigargin, attenuates NO release only from osteoclasts on glass, suggesting that stored Ca2+ has the dominant effect in modulating NO release from non-resorbing cells. NO is a powerful inhibitor of bone resorption: a direct demonstration of its production is therefore strong evidence for a role in modulating osteoclast function.     

Effect of a low-frequency magnetic field on systemic arterial pressure in spontaneously hypertensive rats

The effect of low-frequency magnetic field (MF) on systemic blood pressure has been studied in chronic experiments on 21 spontaneously hypertensive rats. The animals' kidney area was exposed to MF (induction value 30T). Direct blood pressure measurements have revealed an antihypertensive effect.     

Recognition of influenza virus hemagglutinin by subtype-specific and cross-reactive proliferative T cells: contribution of HA1 and HA2 polypeptide chains

The recognition of influenza virus hemagglutinin (HA) by T lymphocytes was examined by assaying the T cell proliferative response of influenza virus-primed T cells to purified HA of different influenza A subtypes or to isolated heavy (HA1) or light (HA2) polypeptide chains of the HA molecule. The proliferative response to HA was dependent on the activation of an Ly-1+2- subset of T cells and required the presence of nylon wool-adherent, radiation-resistant accessory cells. T cells from mice primed by infection with one strain of type A influenza virus cross-reacted with other purified HA not only of the same subtype as the priming virus but also of serologically distinct subtypes of influenza A (but not B) virus. The response of virus-primed T cells to the homologous HA or to HA of the same subtype was shown to involve recognition of determinants on both the HA1 and the HA2 chains. The recognition of HA of different subtype by cross-reactive T cells appeared to be directed predominantly to determinants on HA2. Because the antibody response to influenza virus HA is not cross-reactive between subtypes and is directed predominantly to determinants on HA1, the present results indicate that at least some of the determinants on HA recognized by T cells are different from those recognized by B cells and that the HA2 chain may be involved primarily in stimulation of T cell rather than B cell immunity.     

Sequence Determinants of GLUT1 Oligomerization: ANALYSIS BY HOMOLOGY-SCANNING MUTAGENESIS*

The human blood-brain barrier glucose transport protein (GLUT1) forms homodimers and homotetramers in detergent micelles and in cell membranes, where the GLUT1 oligomeric state determines GLUT1 transport behavior. GLUT1 and the neuronal glucose transporter GLUT3 do not form heterocomplexes in human embryonic kidney 293 (HEK293) cells as judged by co-immunoprecipitation assays. Using homology-scanning mutagenesis in which GLUT1 domains are substituted with equivalent GLUT3 domains and vice versa, we show that GLUT1 transmembrane helix 9 (TM9) is necessary for optimal association of GLUT1-GLUT3 chimeras with parental GLUT1 in HEK cells. GLUT1 TMs 2, 5, 8, and 11 also contribute to a less abundant heterocomplex. Cell surface GLUT1 and GLUT3 containing GLUT1 TM9 are 4-fold more catalytically active than GLUT3 and GLUT1 containing GLUT3 TM9. GLUT1 and GLUT3 display allosteric transport behavior. Size exclusion chromatography of detergent solubilized, purified GLUT1 resolves GLUT1/lipid/detergent micelles as 6- and 10-nm Stokes radius particles, which correspond to GLUT1 dimers and tetramers, respectively. Studies with GLUTs expressed in and solubilized from HEK cells show that HEK cell GLUT1 resolves as 6- and 10-nm Stokes radius particles, whereas GLUT3 resolves as a 6-nm particle. Substitution of GLUT3 TM9 with GLUT1 TM9 causes chimeric GLUT3 to resolve as 6- and 10-nm Stokes radius particles. Substitution of GLUT1 TM9 with GLUT3 TM9 causes chimeric GLUT1 to resolve as a mixture of 6- and 4-nm particles. We discuss these findings in the context of determinants of GLUT oligomeric structure and transport function.     

Bioelectrical Impedance of the Rat Myocardium and Liver under Chronic Exposure to Doxorubicin

Journal of Evolutionary Biochemistry and Physiology - Changes in bioelectrical impedance of the myocardium and liver were revealed in male Wistar rats chronically exposed to doxorubicin....     

Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

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