Heme induces neutrophil migration and reactive oxygen species generation through signaling pathways characteristic of chemotactic receptors

Hemolysis or extensive cell damage can lead to high concentrations of free heme, causing oxidative stress and inflammation. Considering that heme induces neutrophil chemotaxis, we hypothesize that heme activates a G protein-coupled receptor. Here we show that similar to heme, several heme analogs were able to induce neutrophil migration in vitro and in vivo. Mesoporphyrins, molecules lacking the vinyl groups in their rings, were not chemotactic for neutrophils and selectively inhibited heme-induced migration. Moreover, migration of neutrophils induced by heme was abolished by pretreatment with pertussis toxin, an inhibitor of Galpha inhibitory protein, and with inhibitors of phosphoinositide 3-kinase, phospholipase Cbeta, mitogen-activated protein kinases, or Rho kinase. The induction of reactive oxygen species by heme was dependent of Galpha inhibitory protein and phosphoinositide 3-kinase and partially dependent of phospholipase Cbeta, protein kinase C, mitogen-activated protein kinases, and Rho kinase. Together, our results indicate that heme activates neutrophils through signaling pathways that are characteristic of chemoattractant molecules and suggest that mesoporphyrins might prove valuable in the treatment of the inflammatory consequences of hemorrhagic and hemolytic disorders.     

Polyunsaturated fatty acid pattern in liver and erythrocyte phospholipids from obese patients

Objective: Our aim was to study the fatty acid (FA) composition of liver phospholipids and its relation to that in erythrocyte membranes from patients with obese nonalcoholic fatty liver disease (NAFLD), as an indication of lipid metabolism alterations leading to steatosis. Research Methods and Procedures: Eight control subjects who underwent antireflux surgery and 12 obese patients with NAFLD who underwent subtotal gastrectomy with a gastro‐jejunal anastomosis in Roux‐en‐Y were studied. The oxidative stress status of patients was assessed by serum F₂‐isoprostanes levels (gas chromatography/negative ion chemical ionization tandem mass spectrometry). Analysis of FA composition of liver and erythrocyte phospholipids was carried out by gas‐liquid chromatography. Results: Patients with NAFLD showed serum F₂‐isoprostanes levels 84% higher than controls. Compared with controls, liver phospholipids from obese patients exhibited significantly 1) lower levels of 20:4n‐6, 22:5n‐3, 22:6n‐3 [docosahexaenoic acid (DHA)], total long‐chain polyunsaturated FA (LCPUFA), and total n‐3 LCPUFA, 2) higher 22:5n‐6 [docosapentaenoic acid (DPAn‐6)] levels and n‐6/n‐3 LCPUFA ratios, and 3) comparable levels of n‐6 LCPUFA. Levels of DHA and DPAn‐6 in liver were positively correlated with those in erythrocytes (r = 0.77 and r = 0.90, respectively; p < 0.0001), whereas DHA and DPAn‐6 showed a negative association in both tissues (r = ?0.79, p < 0.0001 and r = ?0.58, p < 0.01, respectively), associated with lower DHA/DPAn‐6 ratios. Discussion: Obese patients with NAFLD showed marked alterations in the polyunsaturated fatty acid pattern of the liver. These changes are significantly correlated with those found in erythrocytes, thus suggesting that erythrocyte FA composition could be a reliable indicator of derangements in liver lipid metabolism in obese patients.     

Protein kinase D1 inhibition interferes with mitosis progression

Protein kinase D1 (PKD1) plays a vital role in signal transduction, cell proliferation, membrane trafficking, and cancer; however, the majority of the studies up to date had centered primarily on PKD1 functions in interphase, very little is known about its role during cell division. We previously demonstrated that during mitosis PKD1 is activated and associated with centrosomes, spindles, and midbodies. However, these observations did not address whether PKD1 was associated with mitosis regulation. Accordingly, we used rapidly acting PKD-specific inhibitors to examine the contribution of PKD1 the sequence of events in mitosis. We found that although PKD1 overexpression did not affect mitosis progression, suppression of its catalytic activity by two structurally unrelated inhibitors (kb NB 142-70 and CRT 0066101) induced a significant delay in metaphase to anaphase transition time. PKD1 inhibition during mitosis also produced the appearance of abnormal spindles, defects in chromosome alignment, and segregation as well as apoptosis. Thus, these observations indicate that PKD1 activity is associated with mitosis regulation.     

Rapid shifts in the thermal sensitivity of growth but not development rate causes temperature–size response variability during ontogeny in arthropods

Size at maturity in ectotherms commonly declines with warming. This near‐universal phenomenon, formalised as the temperature–size rule, has been observed in over 80% of tested species, from bacteria to fish. The proximate cause has been attributed to the greater temperature dependence of development rate than growth rate, causing individuals to develop earlier but mature smaller in the warm. However, few studies have examined the ontogenetic progression of the temperature–size response at high resolution. Using marine planktonic copepods, we experimentally determined the progression of the temperature–size response over ontogeny. Temperature–size responses were not generated gradually from egg to adult, contrary to the predictions of a naïve model in which development rate was assumed to be more temperature‐dependent than growth rate, and the difference in the temperature dependence of these two rates remained constant over ontogeny. Instead, the ontogenetic progression of the temperature–size response in experimental animals was highly episodic, indicating rapid changes in the extent to which growth and development rates are thermally decoupled. The strongest temperature–size responses occurred temporally mid‐way through ontogeny, corresponding with the point at which individuals reached between ~5 and 25% of their adult mass. Using the copepod Oithona nana, we show that the temperature‐dependence of growth rate varied substantially throughout ontogeny, whereas the temperature dependence of development rate remained constant. The temperature‐dependence of growth rate even exceeded that of development rate in some life stages, leading to a weakening of the temperature–size response. Our analyses of arthropod temperature–size responses from the literature, including crustaceans and insects, support these conclusions more broadly. Overall, our findings provide a better understanding of how the temperature–size rule is produced over ontogeny. Whereas we find support for the generality of developmental rate isomorphy in arthropods (shared temperature dependence of development rate across life stages), this concept appears not to apply to growth rates.     

Phylogeny of the Augochlora clade with the description of four new species (Hymenoptera,Apoidea)

The Augochlora clade includes four genera: Augochlora Smith, Augochlorella Sandhouse, Ceratalictus Moure, and Pereirapis Moure. This is one of the richest and most widespread groups of Augochlorini bees. There are about 150 species, which occur from Argentina to Canada. The species of Augochlora clade are considered solitary to facultatively social, except Ceratalictus for which nothing is known. Wood nesting behavior arose once in the clade, in Augochlora sensu strictu. The objective of this study is to describe four new species and to present a revised phylogenetic analysis of the Augochlora clade for the placement of these species. The morphological matrix comprised 77 characters and 42 terminals, and resulted in two most parsimonious trees. The monophyly of the Augochlora clade is corroborated. Ceratalictus and Pereirapis are considered as sister groups and Ceratalictus inflexus sp. nov. came as sister to other species of Ceratalictus. Augochlora and Augochlorella are monophyletic and sister groups. Both extant subgenera of Augochlora were corroborated as monophyletic. Augochlorella comis is considered as sister group to the rest of Augochlorella species. All Augochlorella new species described belong to the Augochlorella ephyra group. Augochlorella kelliae sp. nov. is phylogenetically related to Augochlorella una. Augochlorella procliva sp. nov. and Augochlorella mavricera sp. nov. constitute a clade with Augochlorella acarinata. Including the new species, Augochlorella has 19 species and Ceratalictus 11 species. A revised key for species of Augochlorella and Ceratalictus is also presented in the Supplementary Information.