Endocrine function of the heart. Structure and biological properties of peptides secreted by the heart atrium

Apart from the generally known functions, the heart has also an endocrine function. Atrial cardiocytes, being typical secretory cells, release peptide hormones into the blood stream: atrial natriuretic peptide containing 28 amino acids and cardiodilatin. The structure of atrial peptides was determined. It was shown that both peptides were derived from their common precursor, a protein containing 151 amino acids. The presence of specific receptors is demonstrated on plasmatic membranes of cells of kidney epithelium, arterial smooth muscle, arterial endothelium, kidney cortex and hypophysis. The interaction of atrial peptides with these receptors activates the guanylate cyclase system. The biological action of atrial peptides manifests itself in the quick, massive and instantaneous increase of diuresis and electrolyte excretion, elevated clearance of creatinine, decrease of kidney vascular resistance, intensification of glomerular filtration, inhibition of stimulated secretion of aldosterone, relaxation of blood vessels, elimination of arterial and intestinal spasm induced by various endogenous and exogenous vasoconstrictors and in correction of kidney hypertension. Various radioimmunoassays for the presence of atrial peptides in human plasma were developed; it was shown that in patients with congestive heart failure the content of atrial peptides is increased.     

Mechanism of directional selectivity of neurons with complex receptive fields in the cat visual cortex

Spatio-temporal interactions within complex receptive fields in the cat visual cortex were investigated by sequential presentation of two stationary stimuli. When two stimuli were presented in phase (on-on or off-off) in the order corresponding to preferred direction of movement, facilitation or weak inhibition of the response to the second stimulus was observed, whereas if it corresponded to zero direction of movement, the response was strongly inhibited. In the case of stimulation out of phase (on-off or off-on), in the order corresponding to the preferred direction of movement, considerable inhibition of the response to the second stimulus was observed, whereas in the opposite order, facilitation or weak inhibition was observed. The strength of interaction between different parts of the field depended on the distance between them and the duration of the interval between stimuli. Directional selectivity of "complex" neurons is thus ensured by asymmetry of spatio-temporal interactions between receptive field inputs of the same type. Interactions between inputs of different types, arising when a multiedge stimulus (bar, grating) can be used by the visual system to distinguish an object from the background and to assess changes in size of objects and the relative velocity of their movement.V. Kapsukas State University, Vilnius. Translated from Neirofiziologiya, Vol. 16, No. 4, pp. 505–512, July–August, 1984.     

Transcriptional profiling of Zea mays roots reveals roles for jasmonic acid and terpenoids in resistance against Phytophthora cinnamomi

Phytophthora cinnamomi is a soil-borne plant pathogen that has caused widespread damage to vulnerable native ecosystems and agriculture systems across the world and shows no sign of abating. Management of the pathogen in the natural environment is difficult and the options are limited. In order to discover more about how resistant plants are able to defend themselves against this generalist pathogen, a microarray study of plant gene expression following root inoculation with P. cinnamomi was undertaken. Zea mays was used as a resistant model plant, and microarray analysis was conducted using the Affymetrix GeneChip Maize Genome Array on root samples collected at 6- and 24-h post-inoculation. Over 300 genes were differentially expressed in inoculated roots compared with controls across the two time points. Following Gene Ontology enrichment analysis and REVIGO visualisation of the up-regulated genes, many were implicated in plant defence responses to biotic stress. Genes that were up-regulated included those involved in phytoalexin biosynthesis and jasmonic acid/ethylene biosynthesis and other defence-related genes including those encoding glutathione S-transferases and serine-protease inhibitors. Of particular interest was the identification of the two most highly up-regulated genes, terpene synthase11 (Tps11) and kaurene synthase2 (An2), which are both involved in production of terpenoid phytoalexins. This is the first study that has investigated gene expression at a global level in roots in response to P. cinnamomi in a model plant species and provides valuable insights into the mechanisms involved in defence.     

A Genetically Encoded Reporter for Real-Time Imaging of Cofilin-Actin Rods in Living Neurons

Filament bundles (rods) of cofilin and actin (1:1) form in neurites of stressed neurons where they inhibit synaptic function. Live-cell imaging of rod formation is hampered by the fact that overexpression of a chimera of wild type cofilin with a fluorescent protein causes formation of spontaneous and persistent rods, which is exacerbated by the photostress of imaging. The study of rod induction in living cells calls for a rod reporter that does not cause spontaneous rods. From a study in which single cofilin surface residues were mutated, we identified a mutant, cofilinR21Q, which when fused with monomeric Red Fluorescent Protein (mRFP) and expressed several fold above endogenous cofilin, does not induce spontaneous rods even during the photostress of imaging. CofilinR21Q-mRFP only incorporates into rods when they form from endogenous proteins in stressed cells. In neurons, cofilinR21Q-mRFP reports on rods formed from endogenous cofilin and induced by all modes tested thus far. Rods have a half-life of 30–60 min upon removal of the inducer. Vesicle transport in neurites is arrested upon treatments that form rods and recovers as rods disappear. CofilinR21Q-mRFP is a genetically encoded rod reporter that is useful in live cell imaging studies of induced rod formation, including rod dynamics, and kinetics of rod elimination.     

The IRP1-HIF-2α Axis Coordinates Iron and Oxygen Sensing with Erythropoiesis and Iron Absorption

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Highlights? Derepression of HIF-2α mRNA in Irp1^?/? mice causes age-dependent polycythemia ? HIF-2α hyperactivity is observed in multiple tissues of Irp1^?/? mice ? The mRNA regulons of IRP1 and IRP2 are separable in vivo ? The IRP1-HIF-2α axis is a therapeutic target for hematologic or oncologic disorders     

Structural Evaluation and Analyses of Tumor Differentiation Factor

Tumor differentiation factor (TDF) is a protein produced by the pituitary and secreted into the blood stream. The mechanism of its action has still not been elucidated, although the associated protein receptor was identified. Furthermore, the TDF protein does not have any homology with other known proteins, and the crystal structure of TDF also is not available at this time. To gain some insight into the structure of this rather underexplored protein, we have performed a molecular dynamics simulation of a model TDF structure. The structural stability of this protein is evaluated as a function of time. The time dependent structural changes of four cysteine residues present in this structure also are explored.     

Genetic Variants in Epidermal Growth Factor Receptor Pathway Genes and Risk of Esophageal Squamous Cell Carcinoma and Gastric Cancer in a Chinese Population

The epidermal growth factor receptor (EGFR) signaling pathway regulates cell proliferation, differentiation, and survival, and is frequently dysregulated in esophageal and gastric cancers. Few studies have comprehensively examined the association between germline genetic variants in the EGFR pathway and risk of esophageal and gastric cancers. Based on a genome-wide association study in a Han Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for 1942 esophageal squamous cell carcinomas (ESCCs), 1758 gastric cancers (GCs), and 2111 controls. SNP-level analyses were conducted using logistic regression models. We applied the resampling-based adaptive rank truncated product approach to determine the gene- and pathway-level associations. The EGFR pathway was significantly associated with GC risk (P = 2.16×10⁻³). Gene-level analyses found 10 genes to be associated with GC, including FYN, MAPK8, MAP2K4, GNAI3, MAP2K1, TLN1, PRLR, PLCG2, RPS6KB2, and PIK3R3 (P<0.05). For ESCC, we did not observe a significant pathway-level association (P = 0.72), but gene-level analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and ESCC (P<0.05). Our data suggest an association between specific genes in the EGFR signaling pathway and risk of GC and ESCC. Further studies are warranted to validate these associations and to investigate underlying mechanisms.     

Display of functional nucleic acid polymerase on Escherichia coli surface and its application in directed polymerase evolution

We report a first of its kind functional cell surface display of nucleic acid polymerase and its directed evolution to efficiently incorporate 2′-O-methyl nucleotide triphosphates (2′-OMe-NTPs). In the development of polymerase cell surface display, two autotransporter proteins (Escherichia coli adhesin involved in diffuse adherence and Pseudomonas aeruginosa esterase A [EstA]) were employed to transport and anchor the 68-kDa Klenow fragment (KF) of E. coli DNA polymerase I on the surface of E. coli. The localization and function of the displayed KF were verified by analysis of cell outer membrane fractions, immunostaining, and fluorometric detection of synthesized DNA products. The EstA cell surface display system was applied to evolve KF for the incorporation of 2′-OMe-NTPs and a KF variant with a 50.7-fold increased ability to successively incorporate 2′-OMe-NTPs was discovered. Expanding the scope of cell-surface displayable proteins to the realm of polymerases provides a novel screening tool for tailoring polymerases to diverse application demands in a polymerase chain reaction and sequencing-based biotechnological and medical applications. Especially, cell surface display enables novel polymerase screening strategies in which the heat-lysis step is bypassed and thus allows the screening of mesophilic polymerases with broad application potentials ranging from diagnostics and DNA sequencing to replication of synthetic genetic polymers.