Reductions of neural activities to upper airway muscles after elevations in static lung volume.

We evaluated the hypothesis that the tonic discharge of pulmonary stretch receptors significantly influences the respiratory-modulated activities of cranial nerves. Decerebrate and paralyzed cats were ventilated with a servo-respirator, which produced changes in lung volume in parallel with integrated phrenic activity. Activities of the facial, hypoglossal, and recurrent laryngeal nerves and nerves to the thyroarytenoid muscle and triangularis sterni were recorded. After a stereotyped pattern of lung inflation, tracheal pressure was held at 1, 2, 4, or 6 cmH2O during the subsequent ventilatory cycle. Increases in tracheal pressure caused progressive reductions in both inspiratory and expiratory cranial nerve activities and progressive elevations in triangularis sterni discharge; peak levels of phrenic activity declined modestly. Similar changes were observed in normocapnia and hypercapnia. We conclude that the tonic discharge of pulmonary stretch receptors is an important determinant of the presence and magnitude of respiratory-modulated cranial nerve activity. This reflex mechanism may maintain upper airway patency and also regulate expiratory airflow.     

Purification of Trypanosoma cruzi surface proteins involved in adhesion to host cells

We have identified four surface 83 kDa proteins of pI values 6.3, 6.4, 6.5 and 6.6 in T. cruzi trypomastigotes which specifically bind to rat heart myoblasts. These proteins were purified by isoelectric focusing and anion-exchange chromatography in an FPLC system. These 83 kDa proteins inhibit the attachment of trypomastigotes to myoblasts in a concentration-dependent manner, indicating that these trypomastigote proteins mediate the attachment of trypomastigotes to heart myoblasts.     

Formation of 2-methyltryptophan in the biosynthesis of thiostrepton: isolation of S-adenosylmethionine:tryptophan 2-methyltransferase

L-2-Methyltryptophan was found to be an intermediate in the biosynthesis of the antibiotic thiostrepton. It was isolated from growing cultures and resting cells of Streptomyces laurentii in trapping experiments after the application of labeled L-methionine or L-tryptophan. Its formation from L-tryptophan and S-adenosylmethionine was studied in a cell-free extract of S. laurentii. Although several attempts to purify the soluble methyltransferase by standard methods failed, some of its characteristics could be determined in the crude extract. The enzyme has a sharp pH optimum at pH 7.8. The apparent Km value for S-adenosylmethionine is 120 microM and the Ki value for S-adenosylhomocysteine is 480 microM. The enzyme is not stereoselective with respect to D- or L-tryptophan, but the D-isomer is converted at a slower rate than the L-isomer. Indolepyruvic acid is also methylated, while indole is not a substrate. The methyl group is transferred with retention of its configuration, contrary to most other methyltransferase reactions.     

Stabilization of Z-DNA by demethylation of thymine bases: 1.3-A single-crystal structure of d(m5CGUAm5CG)

Methylation of cytosine bases at the C5 position has been known to stabilize Z-DNA. We had previously predicted from calculations of solvent-accessible surfaces that the methyl group at the same position of thymine has a destabilizing effect on Z-DNA. In the current studies, the sequence d(m5CGUAm5CG) has been crystallized and its structure solved as Z-DNA to 1.3-A resolution. A well-defined octahedral hexaaquomagnesium complex was observed to bridge the O4 oxygens of the adjacent uridine bases at the major groove surface, and four well-structured water molecules were found in the minor groove crevice at the d(UA) dinucleotide. These solvent interactions were not observed in the previously published Z-DNA structure of the analogous d(m5CGTAm5CG) sequence. A comparison of the thymine and uridine structures supports our prediction that demethylation of thymine bases helps to stabilize Z-DNA. A comparison of this d(UA)-containing Z-DNA structure with the analogous d(TA) structure shows that access of the O4 position is hindered by the C5 methyl of thymine due to steric and hydrophobic inhibition. In the absence of the methyl group, a magnesium-water complex binds to and slightly affects the structure of the Z-DNA major groove surface. This perturbation of the solvent structure at the major groove surface is translated into a much larger 1.41-A widening of the minor groove crevice, thereby allowing the specific binding of two water molecules at well-defined sites of each internal d(UA) base pair. Possible mechanisms by which modifications at the major groove surface of Z-DNA can affect the solvent properties of the minor groove crevice are discussed.     

Polarized electronic spectra of Z-DNA single crystals

Polarized electronic absorption spectra of the (100) face of single crystals of the Z-form double helical duplex of d(m5CGUAm5CG) have been obtained from Kramers-Kronig analysis of reflection data. The c crystallographic axis is parallel to the helix axis and shows but weak absorption. The b axis is perpendicular to the helix axis and shows a structureless absorption band centered at 270 nm with an oscillator strength of 0.26. Calculations of the crystal spectra utilizing available transition moment data for the individual chromophores are carried through using the oriented gas model (no interbase interactions) and, again, employing all base-base interactions (point dipole) in the duplex. The calculated hypochromism of the 270 nm band is much less than the experimental value obtained from the crystal data. The crystal spectra appear to be representative of Z-form double helices of essentially infinite length and not of a collection of twelve base duplexes. No evidence for n pi* transitions polarized parallel to the helix axis is found.     

Single-cell transcriptomic atlas of primate cardiopulmonary aging

Aging is a major risk factor for many diseases,especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Diseas...     

A Human Active Lower Limb Model for Chinese Pedestrian Safety Evaluation

A subsystem impactor test for pedestrian lower limb injury evaluation has been brought in China New Car Assessment Protocol(CNCAP).Concerning large anthropometr...     

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology