Interleukin-1 beta induces the production of an L-arginine-derived relaxing factor from cultured smooth muscle cells from rat aorta.

The effect of interleukin-1 beta on the production of non-prostanoid vasoactive factors by cultured rat aortic smooth muscle cells was investigated. Under bioassay conditions, the perfusate from a column of confluent cells grown on beads and treated with interleukin-1 beta (1 ng/ml for 18 to 24 hr) abolished the contraction of a canine coronary ring without endothelium contracted by phenylephrine (1 microM), while the perfusate from control cells had no effect. The relaxing activity of the perfusate was observed when transit times were increased from 1 sec to 5 min. Nitro L-arginine (100 microM) reversed the relaxations and L-arginine stereoselectively restored the relaxations. Interleukin-1 beta (1 ng/ml) evoked a time-dependent accumulation of cyclic GMP but not cyclic AMP in cultured smooth muscle cells. The transfer of fresh or stored (-70 degrees C) conditioned culture medium from interleukin-1 beta-treated cells but not from control cells, to cultured smooth muscle cells stimulated the production of cyclic GMP. These observations demonstrate that interleukin-1 beta induces the production of transferable factor which relaxes vascular smooth muscle and stimulates the production of cyclic GMP.     

Adrenergic pharmacology of human and canine peripheral veins

A comparison has been made of the factors concerned with the response of canine and human saphenous veins to adrenergic stimulation. Both vessels have prejunctional muscarinic and beta-adrenergic receptors. When activated by appropriate agonists these receptors decrease and increase the output, respectively, of norepinephrine from the nerve endings. Both vessels have postjunctional alpha 1 and alpha 2 adrenoceptors and postjunctional beta adrenoceptors. Activation of the former two receptors leads to contraction of the smooth muscle, and of the latter to relaxation. There are, however, qualitative differences. In the human veins the responsiveness of the prejunctional beta adrenoceptors exceeds that of the postjunctional, whereas the reverse is true in the dog. As a consequence, in the human vein beta-adrenergic agonists augment, and in the canine veins they depress, the contractile response to sympathetic nerve stimulation.     

Dry-season spawning in a cyprinid fish of southern India

Synopsis A population of the S. Indian cyprinid fishBarbus melanampyx was sampled monthly through 24 months. Seasonal cycles of the gonado-somatic index (GSI), ovarian stages, male breeding tubercles, spawning behaviour and population structure were assessed. These fish breed strictly seasonally during the main dry period: December/January through April. Comparison with other Barbus species of the same general region led to the conclusion that the patterns of reproductive investment ofB. melanampyx are similar to those of perennial species, and different from those of wet-season spawners. The reasons for this rather unexpected result were found in the more constant conditions prevailing during a dry season as compared to the monsoon. It was argued thatB. melanampyx and the species spawning perennially are in effect small-brood spawners, rather than partial spawners.     

On some generative orders of behaviour

The sociobiological fashion has for a long time discouraged the development of theories of the immediate causation of behaviour. It is only recently that new approaches are being developed to improve on the classical ethological theory originated by Lorenz and Tinbergen. One new departure is behavioural field theory (BFT) which brings back the concept of energy in behaviour, without being susceptible to the drawbacks of the energy or fuel concept of classical theory. In this paper the new theory is explained in some detail and it is shown to be illuminating, predictive and testable in examples of play-like and territorial behaviour.     

Acetylcholine--inhibition of transmitter release from adrenergic nerve terminals mediated by muscarinic receptors.

The evidence is reviewed for the presence of muscarinic receptors on the sympathetic nerves to blood vessels. Activation of these receptors by acetylcholine in doses that are too small to affect the smooth muscle cells directly inhibits the release of norepinephrine evoked by electric impulses or potassium ions. This inhibitory action of acetylcholine is prevented by muscarinic blocking agents and is probably due to hyperpolarization of the adrenergic nerve terminals.     

Metabolic modulation of neurotransmitter release--adenosine, adenine nucleotides, potassium, hyperosmolarity, and hydrogen ion.

Evidence has accumulated that several factors, which have been proposed as mediators of exercise hyperemia, can modulate adrenergic neurotransmission in blood vessels. Adenosine and the adenine nucleotides depress the response of isolated blood vessels of the dog to nerve stimulation more than that to exogenous norepinephrine; this difference is explained by a decreased release of the neurotransmitter. Potassium, hyperosmolarity, and acidosis also depress adrenergic neurotransmission in isolated veins. These results are consistent with the hypothesis that metabolic changes in the vicinity of the adrenergic neuroeffector junction are capable of decreasing the output of neurotransmitter to the blood vessels in the exercising muscle.     

Vesicular trafficking permits evasion of cGAS/STING surveillance during initial human papillomavirus infection

Oncogenic human papillomaviruses (HPVs) replicate in differentiating epithelium, causing 5% of cancers worldwide. Like most other DNA viruses, HPV infection initiates after trafficking viral genome (vDNA) to host cell nuclei. Cells possess innate surveillance pathways to detect microbial components or physiological stresses often associated with microbial infections. One of these pathways, cGAS/STING, induces IRF3-dependent antiviral interferon (IFN) responses upon detection of cytosolic DNA. Virion-associated vDNA can activate cGAS/STING during initial viral entry and uncoating/trafficking, and thus cGAS/STING is an obstacle to many DNA viruses. HPV has a unique vesicular trafficking pathway compared to many other DNA viruses. As the capsid uncoats within acidic endosomal compartments, minor capsid protein L2 protrudes across vesicular membranes to facilitate transport of vDNA to the Golgi. L2/vDNA resides within the Golgi lumen until G2/M, whereupon vesicular L2/vDNA traffics along spindle microtubules, tethering to chromosomes to access daughter cell nuclei. L2/vDNA-containing vesicles likely remain intact until G1, following nuclear envelope reformation. We hypothesize that this unique vesicular trafficking protects HPV from cGAS/STING surveillance. Here, we investigate cGAS/STING responses to HPV infection. DNA transfection resulted in acute cGAS/STING activation and downstream IFN responses. In contrast, HPV infection elicited minimal cGAS/STING and IFN responses. To determine the role of vesicular trafficking in cGAS/STING evasion, we forced premature viral penetration of vesicular membranes with membrane-perturbing cationic lipids. Such treatment renders a non-infectious trafficking-defective mutant HPV infectious, yet susceptible to cGAS/STING detection. Overall, HPV evades cGAS/STING by its unique subcellular trafficking, a property that may contribute to establishment of infection.     

Food availability affects the strength of mutualistic host–microbiota interactions in Daphnia magna

The symbiotic gut microbial community is generally known to have a strong impact on the fitness of its host. Nevertheless, it is less clear how the impact of symbiotic interactions on the hosts'' fitness varies according to environmental circumstances such as changes in the diet. This study aims to get a better understanding of host–microbiota interactions under different levels of food availability. We conducted experiments with the invertebrate, experimental model organism Daphnia magna and compared growth, survival and reproduction of conventionalized symbiotic Daphnia with germ-free individuals given varying quantities of food. Our experiments revealed that the relative importance of the microbiota for the hosts'' fitness varied according to dietary conditions. The presence of the microbiota had strong positive effects on Daphnia when food was sufficient or abundant, but had weaker effects under food limitation. Our results indicate that the microbiota can be a potentially important factor in determining host responses to changes in dietary conditions. Characterization of the host-associated microbiota further showed that Aeromonas sp. was the most prevalent taxon in the digestive tract of Daphnia.     

A clinical experience with perforator flaps in the coverage of extensive defects of the upper extremity

Traditional skin free flaps, such as radial arm, lateral arm, and scapular flaps, are rarely sufficient to cover large skin defects of the upper extremity because of the limitation of primary closure at the donor site. Muscle or musculocutaneous flaps have been used more for these defects. However, they preclude a sacrifice of a large amount of muscle tissue with the subsequent donor-site morbidity. Perforator or combined flaps are better alternatives to cover large defects. The use of a muscle as part of a combined flap is limited to very specific indications, and the amount of muscle required is restricted to the minimum to decrease the donor-site morbidity. The authors present a series of 12 patients with extensive defects of the upper extremity who were treated between December of 1999 and March of 2002. The mean defect was 21 x 11 cm in size. Perforator flaps (five thoracodorsal artery perforator flaps and four deep inferior epigastric perforator flaps) were used in seven patients. Combined flaps, which were a combination of two different types of tissue based on a single pedicle, were needed in five patients (scapular skin flap with a thoracodorsal artery perforator flap in one patient and a thoracodorsal artery perforator flap with a split latissimus dorsi muscle in four patients). In one case, immediate surgical defatting of a deep inferior epigastric perforator flap on a wrist was performed to immediately achieve thin coverage. The average operative time was 5 hours 20 minutes (range, 3 to 7 hours). All but one flap, in which the cutaneous part of a combined flap necrosed because of a postoperative hematoma, survived completely. Adequate coverage and complete wound healing were obtained in all cases. Perforator flaps can be used successfully to cover a large defect in an extremity with minimal donor-site morbidity. Combined flaps provide a large amount of tissue, a wide range of mobility, and easy shaping, modeling, and defatting.