A new role for PGRP-S (Tag7) in immune defense: lymphocyte migration is induced by a chemoattractant complex of Tag7 with Mts1

PGRP-S (Tag7) is an innate immunity protein involved in the antimicrobial defense systems, both in insects and in mammals. We have previously shown that Tag7 specifically interacts with several proteins, including Hsp70 and the calcium binding protein S100A4 (Mts1), providing a number of novel cellular functions. Here we show that Tag7–Mts1 complex causes chemotactic migration of lymphocytes, with NK cells being a preferred target. Cells of either innate immunity (neutrophils and monocytes) or acquired immunity (CD4⁺ and CD8⁺ lymphocytes) can produce this complex, which confirms the close connection between components of the 2 branches of immune response.     

Carvedilol Prevents Ovariectomy-Induced Myocardial Contractile Dysfunction in Female Rat

Carvedilol has beneficial effects on cardiac function in patients with heart failure but its effect on ovariectomy-induced myocardial contractile dysfunction remains unclear. Estrogen deficiency induces myocardial contractile dysfunction and increases cardiovascular disease risk in postmenopausal women. Our aim was to investigate whether carvedilol, a beta receptor blocker, would prevent ovariectomy-induced myocardial contractile dysfunction. Female rats (8 weeks old) that underwent bilateral ovariectomy were randomly assigned to receive daily treatment with carvedilol (OVX+CAR, 20 mg/kg), placebo (OVX) and SHAM for 58 days. Left ventricle papillary muscle was mounted for isometric tension recordings. The inotropic response to Ca²⁺ (0.62 to 3.75 mM) and isoproterenol (Iso 10⁻⁸ to 10⁻² M) were assessed. Expression of calcium handling proteins was measured by western blot analysis. Carvedilol treatment in the OVX animals: prevented weight gain and slight hypertrophy, restored the reduced positive inotropic responses to Ca²⁺ and isoproterenol, prevented the reduction in SERCA2a expression, abolished the increase in superoxide anion production, normalized the increase in p22^phox expression, and decreased serum angiotensin converting enzyme (ACE) activity. This study demonstrated that myocardial contractile dysfunction and SERCA2a down regulation were prevented by carvedilol treatment. Superoxide anion production and NADPH oxidase seem to be involved in this response.     

Ontogenetic integration between force production and force reception: a case study in Ctenomys (Rodentia: Caviomorpha)

During ontogeny, complex adaptations undergo changes that sometimes entail different functional capabilities. This fact constrains the behaviour of organisms at each developmental stage. Rodents have ever‐growing incisors for gnawing, and a powerful jaw musculature. The incisors are long enough, relative to their diameter, to be affected by bending stresses. This is particularly true in the subterranean Ctenomys that uses its incisors for digging. We measured bite force (BF) in individuals of different ages using a force transducer. We estimated incisor section modulus Z, a geometrical parameter proportional to bending strength. A relative strength indicator was calculated as S = Z/BF incisor length. We found that ontogenetic BF scales to body mass with positive allometry. However, an anova showed non‐significant differences in S, neither between sexes nor among age classes. This result implies that during growth, incisors might have a rather similar ability to withstand bending stresses from increasing masticatory forces, what may be considered evidence of ontogenetic integration of force production (by muscles) and force reception (by the incisors). This fact well correlates with the observation that pups and juveniles of C. talarum incorporate solid foods shortly after birth, and they are able to dig burrows early in life.     

Connectivity in the network macrostructure of Tursiops truncatus in the Pelagos Sanctuary (NW Mediterranean Sea): does landscape matter?

The bottlenose dolphin (Tursiops truncatus Montagu, 1821) is a regularly observed species in the Mediterranean Sea, but its network organization has never been investigated on a large scale. We described the network macrostructure of the bottlenose dolphin (meta)population inhabiting the Pelagos Sanctuary (a wide protected area located in the north-western portion of the Mediterranean basin) and we analysed its connectivity in relation to the landscape traits. We pooled effort and sighting data collected by 13 different research institutions operating within the Pelagos Sanctuary from 1994 to 2011 to examine the distribution of bottlenose dolphins in the Pelagos study area and then we applied a social network analysis, investigating the association patterns of the photo-identified dolphins (806 individuals in 605 sightings). The bottlenose dolphin (meta)population inhabiting the Pelagos Sanctuary is clustered in discrete units whose borders coincide with habitat breakages. This complex structure seems to be shaped by the geo-morphological and ecological features of the landscape, through a mechanism of local specialization of the resident dolphins. Five distinct clusters were identified in the (meta)population and two of them were solid enough to be further investigated and compared. Significant differences were found in the network parameters, suggesting a different social organization of the clusters, possibly as a consequence of the different local specialization.     

Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors

The involvement of nitric oxide (NO), prostaglandins, and calcium-dependent potassium channel (K(Ca)) activators on the negative modulation of phenylephrine-induced contractions was evaluated on the isolated aorta and caudal (CAU) artery obtained from rats treated with ouabain for 5 wk to induce hypertension. In ouabain-treated rats, the reactivity to phenylephrine was reduced in the endothelium-intact aorta but not the CAU segments. Endothelial modulation of phenylephrine contraction, as demonstrated by endothelium removal, NO synthase (NOS) inhibition with N(omega)-nitro-L-arginine methyl ester and aminoguanidine, as well as K(Ca) inhibition with tetraethylammonium, was more pronounced in segments from ouabain-treated animals, and here greater effects were seen in the aorta than in CAU. An increased expression of endothelial NOS and neuronal NOS was seen in the aorta after ouabain treatment. In CAU, only endothelial NOS was detected and ouabain treatment did not alter its expression. These results suggest that ouabain-induced hypertension is accompanied by increased NO release derived from endothelial NOS and neuronal NOS and increased release of an endothelial hyperpolarizing factor that presumably opens K(Ca), all of which contribute to the increased negative modulation of the phenylephrine contraction.     

Isolated Pneumocystis carinii cell wall glucan provokes lower respiratory tract inflammatory responses

Macrophage-induced lung inflammation contributes substantially to respiratory failure during Pneumocystis carinii pneumonia. We isolated a P. carinii cell wall fraction rich in glucan carbohydrate, which potently induces TNF-alpha and macrophage-inflammatory protein-2 generation from alveolar macrophages. Instillation of this purified P. carinii carbohydrate cell wall fraction into healthy rodents is accompanied by substantial increases in whole lung TNF-alpha generation and is associated with neutrophilic infiltration of the lungs. Digestion of the P. carinii cell wall isolate with zymolyase, a preparation containing predominantly beta-1,3 glucanase, substantially reduces the ability of this P. carinii cell wall fraction to activate alveolar macrophages, thus suggesting that beta-glucan components of the P. carinii cell wall largely mediate TNF-alpha release. Furthermore, the soluble carbohydrate beta-glucan receptor antagonists laminariheptaose and laminarin also substantially reduce the ability of the P. carinii cell wall isolate to stimulate macrophage-inflammatory activation. In contrast, soluble alpha-mannan, a preparation that antagonizes macrophage mannose receptors, had minimal effect on TNF-alpha release induced by the P. carinii cell wall fraction. P. carinii beta-glucan-induced TNF-alpha release from alveolar macrophages was also inhibited by both dexamethasone and pentoxifylline, two pharmacological agents with potential activity in controlling P. carinii-induced lung inflammation. These data demonstrate that P. carinii beta-glucan cell wall components can directly stimulate alveolar macrophages to release proinflammatory cytokines mainly through interaction with cognate beta-glucan receptors on the phagocyte.     

Stimulation of yeast 3-phosphoglycerate kinase gene promoter by paraquat

Yeast cells exposed to adverse conditions employ a number of defense mechanisms in order to respond effectively to the stress and sustain a high proliferation rate. It has been shown that several glycolytic enzymes are induced upon heat treatment of yeast. In this work, we used a reporter plasmid construct to study the effects of oxidative stress, induced by the O(*-)(2)-generating compound paraquat (PQ), on the yeast 3-phosphoglycerate kinase gene (PGK) promoter. Our results show that (i) moderate, as opposed to excessive, doses of PQ induce increased stimulation of the PGK promoter, at midlogarithmic phase of growth; and (ii) the thiol antioxidant N-acetylcysteine cancels this stimulatory effect. These observations may represent one aspect of a more general role for glycolysis in maintaining the energy pools of yeast cells under stress.     

Low-level lead exposure increases systolic arterial pressure and endothelium-derived vasodilator factors in rat aortas

Chronic lead exposure induces hypertension and alters endothelial function. However, treatment with low lead concentrations was not yet explored. We analyzed the effects of 7 day exposure to low lead concentrations on endothelium-dependent responses. Wistar rats were treated with lead (1st dose 4 μg/100 g, subsequent dose 0.05 μg/100 g, i.m. to cover daily loss) or vehicle; blood levels attained at the end of treatment were 9.98 μg/dL. Lead treatment had the following effects: increase in systolic blood pressure (SBP); reduction of contractile response to phenylephrine (1 nM-100 μM) of aortic rings; unaffected relaxation induced by acetylcholine (0.1 nM-300 μM) or sodium nitroprusside (0.01 nM-0.3 μM). Endothelium removal, N(G)-nitro-L-arginine methyl ester (100 μM) and tetraethylammonium (2 mM) increased the response to phenylephrine in treated rats more than in untreated rats. Aminoguanidine (50 μM) increased but losartan (10 μM) and enalapril (10 μM) reduced the response to phenylephrine in treated rats. Lead treatment also increased aortic Na(+)/K(+)-ATPase functional activity, plasma angiotensin-converting enzyme (ACE) activity, protein expression of the Na(+)/K(+)-ATPase alpha-1 subunit, phosphorylated endothelial nitric oxide synthase (p-eNOS), and inducible nitric oxide synthase (iNOS). Our results suggest that on initial stages of lead exposure, increased SBP is caused by the increase in plasma ACE activity. This effect is accompanied by increased p-eNOS, iNOS protein expression and Na(+)/K(+)-ATPase functional activity. These factors might be a compensatory mechanism to the increase in SBP.