From hindbrain segmentation to breathing after birth: developmental patterning in rhombomeres 3 and 4

Respiration is a rhythmic motor behavior that appears in the fetus and acquires a vital importance at birth. It is generated within central pattern-generating neuronal networks of the hindbrain. This region of the brain is of particular interest since it is the most understood part with respect to the cellular and molecular mechanisms that underlie its development. Hox paralogs and Hox-regulating genes kreisler/mafB and Krox20 are required for the normal formation of rhombomeres in vertebrate embryos. From studies of rhombomeres r3 and r4, the authors review mechanisms whereby these developmental genes may govern the early embryonic development of para-facial neuronal networks and specify patterns of motor activities operating throughout life. A model whereby the regional identity of progenitor cells can be abnormally specified in r3 and r4 after a mutation of these genes is proposed. Novel neuronal circuits may develop from some of these misspecified progenitors while others are eliminated, eventually affecting respiration and survival after birth.     

Helicobacter pylori infection in children and adults: a single pathogen but a different pathology

Background. The aims of this retrospective study were to ascertain in large series of children and adults: the relationship of the infecting strain to gastric mucosal lesions; and the relationship of the infecting strain to its duodenal localization. Materials and Methods. We studied 307 and 604 consecutive children and adults. In gastric mucosal samples H. pylori was cultured, genotyped and histologically assessed, while inflammation, activity and intestinal metaplasia were graded. In a subset of 171 patients H. pylori ureaseA (ureA) and cagA genes were amplified (PCR) using mucosal biopsies from the duodenum. Results. H. pylori infection was diagnosed in 40 children and 308 adults. cagA was identified in 50% and 65.5% of infected children and adults. Antral activity was associated with the density of infecting bacteria (p < .001) and with cagA (p < .01). Intestinal metaplasia was correlated with cagA (p < .001). The ureA gene was found in 56 duodenal samples from 82 H. pylori positive patients. Duodenal H. pylori ureA was significantly more frequent in patients with duodenal diseases than in those without (p < .01), cagA positive strains being mainly involved in the infection of this anatomical area (p < .01). Conclusions. A severe H. pylori‐associated gastritis is more prevalent when the density of infecting bacteria is high and when cagA positive strains cause the infection. The most virulent cagA positive H. pylori colonizes not only the gastric, but also the duodenal mucosa, which can be directly damaged by the bacteria itself or by its products.     

Conflict resolution following aggression in gregarious animals: a predictive framework

Knowledge of how animals manage their conflicts is critical for understanding the dynamics of social systems. During the last two decades research on gregarious animals, especially primates, has focused on the mechanisms of conflict management, mainly on friendly postconflict reunions (also called ‘reconciliation’) in which former opponents exchange affiliative behaviour soon after an aggressive conflict. Our aim in this paper is to present a framework in which the costs and benefits of friendly postconflict reunions, both for each individual opponent and for their mutual relationship, are used to predict the patterning of postconflict resolution mechanisms in other gregarious animals. The framework predicts the occurrence of postconflict reunions in species that live in stable social units, have individualized relationships, and experience postconflict hostility, but especially in those in which intragroup aggression disrupts valuable relationships. The critical issue is whether aggressive conflicts occur between cooperative partners and whether the level of aggression is sufficient to jeopardize the benefits associated with such valuable relationships. We conclude by proposing four research priorities to evaluate the role of friendly reunions in negotiating relationships and the way they are themselves influenced by asymmetries in partner value and biological market effects. Copyright 2002 The Association for the Study of Animal Behaviour. Published by Elsevier Science Ltd. All rights reserved.     

Not-adaptive behavior of isotropically heated, inert populations of Oxytricha bifaria (Ciliophora, Stichotrichia)

The physiological effects on isotropically heated populations of Oxytricha bifaria cultured at 24 degrees C were investigated. At 34.6 degrees C ciliates became inert, and did not adaptively react to either cold or warm microgradients; they neither moved towards the favorable cold thermal source nor escaped from the unfavorable warm one. The inert oxytrichas were only able to perform the Side-Stepping Reaction (SSR) on the same spot. However, mobile ciliates at 31.6 degrees C reacted to the cold microgradient by immediately orienting themselves towards its source, without accelerating but reducing their SSR frequency. Moreover, in a warm microgradient such ciliates immediately increased their SSR frequency, then moved away from the thermal source. At 34.6 degrees C the behavior of ciliates was not-adaptive--not acting to guide the organisms to more favorable conditions--whereas at 31.6 degrees C it was still clearly adaptive. Therefore, the locomotory inertness of the oxytrichas at 34.6 degrees C was the result of thermal stress rather than their behavioral response to the environmental isotropy, in contrast to populations of the same species made inert at 9 degrees C.     

Following the rules: why small groups of tamarins do not reconcile conflicts

Reconciliation is the post-conflict friendly reunion between opponents. A series of conditions and rules in order for reconciliation to take place has been recently proposed. One critical condition is that the relationship between opponents must be disrupted. We tested this condition using post-conflict and matched-control observations on 4 small groups of tamarins (Saguinus labiatus). Our previous lack of evidence for reconciliation was confirmed. No post-conflict relationship damage was therefore expected. We found evidence that relationships were disturbed following conflicts over food but, as in other primates, no evidence for reconciliation following such conflicts was found. For non-food-related conflicts there was no evidence that relationships were disturbed, as opponents were in close proximity to each other and resumed the exact same activity as frequently in the post-conflict observations as they did in the matched-control observations. We conclude that 'everyday' aggression may not disrupt the relationships among individuals from the same family group and therefore reconciliation is not needed.     

Complexes of Ag with mixed donor phenanthroline-containing macrocycles: spectrofluorimetric, spectrophotometric, conductometric and potentiometric studies

The reactions of Ag⁺ with five mixed donor phenanthroline-containing macrocycles (L¹-L⁵) having N₂S₃-, N₂S₂O-, N₂S₂-, N₃S₂-, and N₄S₂-donor sets, respectively, have been studied in MeCN by spectrofluorimetric, spectrophotometric, conductometric and potentiometric methods. All ligands form 1:1 [Ag(L)]⁺ complexes, and in the case of L⁴ and L⁵, formation of 1:2 [Ag(L)₂]⁺ species is also observed. The corresponding formation constants have been evaluated and their values allow a deeper insight into the role played by complexation process in the potentiometric selectivity for Ag⁺ of membrane electrodes (ISE), and in the selective transport of Ag⁺ through supported liquid membrane (SLM) systems based on these ligands. The X-ray crystal structure of the complex [Ag(L⁴)]BF₄ is also reported.     

S-palmitoylation modulates human estrogen receptor-alpha functions

17beta-Estradiol (E2)-induced rapid functions (from seconds to minutes) can be attributed to a fraction of nuclear estrogen receptor-alpha (ERalpha) localized at the plasma membrane. As a potential mechanism, we postulated that S-palmitoylation of the Cys447 residue may explain the ability of ERalpha to associate to plasma membrane making possible E2-dependent rapid functions [e.g., extracellular regulated kinase (ERK) activation]. Here, we report direct evidence that the mutation of the Cys447 residue to Ala impairs human ERalpha palmitoylation and E2-induced rapid ERK phosphorylation when transfected in ER-devoid HeLa cells. Moreover, the Cys447Ala mutation significantly decreases the E2-induced transactivation of an estrogen responsive element construct probe. Similar effects were obtained treating HeLa cells transfected with wild type ERalpha with the palmitoyl-acyltransferase inhibitor 2-bromo-hexadecanoic acid. Moreover, the deletion of the A-D domains (containing the DNA binding region) of ERalpha had no consequences on [(3)H]palmitate incorporation, whereas no palmitoylation occurred in the ERalpha mutant devoid of the E domain (i.e., ligand binding domain). These results point to the pivotal role of the Cys447 residue in ERalpha palmitoylation and in the modulation of E2-induced non-genomic functions.     

Maternally-inherited Leigh syndrome-related mutations bolster mitochondrial-mediated apoptosis

The key role of mitochondria in the apoptotic process is well understood, but not many data are available regarding the specific role of mitochondrial DNA mutations in determining cell fate. We investigated whether two mitochondrial DNA mutations (L217R and L156R) associated with maternally-inherited Leigh syndrome may play a specific role in triggering the apoptotic cascade. Considering that different nuclear genetic factors may influence the expression of mtDNA mutations, we used a 143BTK(-) osteosarcoma cell line deprived from its own mtDNA in order to insert mutated mtDNAs. Analysis of mitochondrial features in these cybrids indicated that both mitochondrial DNA mutations produced evidence of biochemical, functional and ultrastructural modifications of mitochondria, and that these modifications were associated with an increased apoptotic proneness. Cybrids were highly susceptible to two different apoptotic stimuli, tumour necrosis factor-alpha and Staurosporin. The mechanism involved was the mitochondrial 'intrinsic' pathway, i.e. the caspase 9-driven cascade. More importantly, our results also indicated that the polarization state of the mitochondrial membrane, i.e. a constitutive hyperpolarization detected in cybrid clones, played a specific role. Interestingly, the different effects of the two mutations in terms of susceptibility to apoptosis probably reflect the deeper bioenergetic defect associated with the L217R mutation. This work provides the first evidence that hyperpolarization of mitochondria may be a 'risk factor' for cells with a deep ATPase dysfunction, such as cells from patients with maternally-inherited Leigh syndrome.     

Human immunodeficiency virus type 1 gp120 induces abnormal maturation and functional alterations of dendritic cells: a novel mechanism for AIDS pathogenesis

Dendritic cells (DCs) play a crucial role in bridging innate and acquired immune responses to pathogens. In human immunodeficiency virus type 1 (HIV-1) infection, immature DCs (iDCs) are also main targets for HIV-1 at the mucosal level. In this study, we evaluated the effects of HIV-1-DC interactions on the maturation and functional activity of these cells. Exposure of human monocyte-derived iDCs to either aldrithiol-2-inactivated HIV-1 or gp120 led to an upmodulation of activation markers indicative of functional maturation. Despite their phenotype, these cells retained antigen uptake capacity and showed an impaired ability to secrete cytokines or chemokines and to induce T-cell proliferation. Although gp120 did not interfere with DC differentiation, the capacity of these cells to produce interleukin-12 (IL-12) upon maturation was markedly reduced. Likewise, iDCs stimulated by classical maturation factors in the presence of gp120 lacked allostimulatory capacity and did not produce IL-12, in spite of their phenotype typical of activated DCs. Exogenous addition of IL-12 restores the allostimulatory capacity of gp120-exposed DCs. The finding that gp120 induces abnormal maturation of DCs linked to profound suppression of their activities unravels a novel mechanism by which HIV can lead to immune dysfunction in AIDS patients.     

Adipose compartments of the upper eyelid: anatomy applied to blepharoplasty

Many authors have indicated the presence of ectopic or accessory upper eyelid fat pads, but the effective rate of eyelid fat variations and the corresponding clinical features are still unclear. The purpose of this study was to evaluate the variability of upper lid fat and to define the anatomical landmarks of the adipose pockets of the upper lid. From January of 1998 to January of 2002, the authors investigated the upper eyelid fat compartments of 47 patients who underwent upper blepharoplasty. To support surgical findings, 11 fresh cadavers were also investigated; the anatomy of the intraorbital fat and of the upper eyelid fat compartments was reviewed. Ten patients (21.3 percent) showed an accessory fat pad in the upper lid, which was found on both sides in nine cases. In all patients, the third fat pad was situated lateral to the two classic compartments described by Castanares, behind the orbital septum. Surgical dissections demonstrated that this fat pad derived from the preaponeurotic fat. Anatomical dissections in three cadavers demonstrated an accessory fat compartment protruding under the inferior border of the lacrimal gland. This protruding fat derived from the preaponeurotic fat in all cases and might justify the clinical appearance of a bulge or fullness in the lateral third of the upper eyelid. In the authors' experience, the presence of an accessory upper eyelid fat pad was a frequent finding during blepharoplasty; it could be found and actually resected in about 21 percent of all cases. Surgical and experimental findings put this element as a lateral physiological extension of the preaponeurotic fat that can anteriorly protrude under the inferior border of the lacrimal gland toward the orbital septum. The clinical appearance may be a bulge or fullness in the upper eyelid, and its resection can better define the lateral one third of the supratarsal fold.