Molecular mechanisms of perineural invasion,a forgotten pathway of dissemination and metastasis

Invasion and metastasis are key components of cancer progression. Inflammatory mediators, including cytokines and chemokines, can facilitate tumor dissemination. A distinct and largely forgotten path is perineural invasion (PNI), defined as the presence of cancer cells in the perinerium space. PNI is frequently used by many human carcinomas, in particular by pancreas and prostate cancer, and is associated with tumor recurrence and pain in advanced patients. Neurotrophic factors have been identified as molecular determinants of PNI. A role for chemokines in this process has been proposed; the chemokine CX3CL1/Fractalkine attracts receptor positive pancreatic tumor cells to disseminate along peripheral nerves. Better understanding of the neurotropism of malignant cells and of the clinical significance of PNI would help the design of innovative strategies for the control of tumor dissemination and pain in cancer patients.     

The importance of location and visual cues during foraging in the German wasp (Vespula germanica F.) (Hymenoptera: Vespidae)

Abstract

The way in which foraging wasps use cues for prey location and choice appears to depend on both the context and on the type of prey. Vespula germanica is an opportunistic, generalist prey forager, and individual wasp foragers often return to hunt at sites of previous hunting success. In this paper, we studied which cues are used by this wasp when relocating a food source. Particularly we analysed the response to a displaced visual cue versus a foraging location at which either honey or cat food had been previously presented. We conclude that location is used over a displaced visual cue for directing wasp hovering, although the landing response is directed differently according to bait type. When wasps are exploiting cat food, location also elicits landing, but if they are exploiting honey, a displaced visual cue elicits landing more frequently than location.     

Effects of prolonged cycle ergometer exercise on maximal muscle power and oxygen uptake in humans

The mechanical power (W_tot, W·kg^–1) developed during ten revolutions of all-out periods of cycle ergometer exercise (4–9 s) was measured every 5–6 min in six subjects from rest or from a baseline of constant aerobic exercise [50%–80% of maximal oxygen uptake (VO_2max)] of 20–40 min duration. The oxygen uptake [VO₂ (W·kg^–1, 1 ml O₂ = 20.9 J)] and venous blood lactate concentration ([la]_b, mM) were also measured every 15 s and 2 min, respectively. During the first all-out period, W_tot decreased linearly with the intensity of the priming exercise (W_tot = 11.9–0.25·VO₂). After the first all-out period (i greater than 5–6 min), and if the exercise intensity was less than 60% VO_2max, W_tot, VO₂ and [la]_b remained constant until the end of the exercise. For exercise intensities greater than 60% VO_2max, VO₂ and [la]_b showed continuous upward drifts and W_tot continued decreasing. Under these conditions, the rate of decrease of W_tot was linearly related to the rate of increase of V [(d W_tot/dt) (W·kg^–1·s^–1) = 5.0·10^–5 –0.20·(d VO₂/dt) (W·kg^–1·s^–1)] and this was linearly related to the rate of increase of [la]_b [(d VO₂/dt) (W·kg^–1·s^–1) = 2.310^–4 + 5.910^–5·(d [la]_b/dt) (mM·s^–1)]. These findings would suggest that the decrease of W_tot during the first all-out period was due to the decay of phosphocreatine concentration in the exercising muscles occurring at the onset of exercise and the slow drifts of VO₂ (upwards) and of W_tot (downwards) during intense exercise at constant W_tot could be attributed to the continuous accumulation of lactate in the blood (and in the working muscles).     

Factors Affecting Interspecific Aggression in a Year‐Round Territorial Species,the Jewel Damselfish

Vertebrates live in complex species networks in which interspecific interactions are common. In some contexts, the aggressive behaviours shown in these interspecific interactions are very similar to those shown in intraspecific interactions. It is still an open question whether intra‐ and interspecific aggression share common causality. We studied a year‐round territorial species the jewel damselfish, (Plectroglyphidodon lacrymatus), which cultivate algae they feed on. Territory holders aggressively defend these algae that are an attractive resource for many other species. In this study, we recorded territorial aggression in free‐living individuals and recorded aggressive responses to a standardized territorial intrusion test in captive individuals. Field observations indicated that territorial aggression was selectively targeted towards food competitors. Independent of the size of the species, aggression was more frequent towards common species around their territories. This relationship was confirmed experimentally by confronting the jewel damselfish with novel objects to which the subjects were exposed either frequently or rarely. We suggest that jewel damselfish have to learn which species are competitors and therefore should be chased. In a standardized intrusion test with captive individuals, no significant differences were found in territorial responses towards intra‐ or interspecific intruders. Neither territorial aggression nor the intrusion showed any relationship with plasma androgen levels. Together, these data suggest that experience might be more important in non‐seasonal territorial aggression than circulating hormonal factors.     

Stereological and functional investigations on isolated adrenocortical cells: Zona fasciculata/reticularis cells of chronically ACTH-treated rats

Summary The morphology and function of isolated inner (zona fasciculata/reticularis) adrenocortical cells of rats pretreated with ACTH for 3, 6, 9 or 12 days were investigated. ACTH treatment induced a notable time-dependent enhancement in the steroidogenic capacity (corticosterone production) and growth of inner cells. The volumes of cells, mitochondrial compartment, membrane space [the cellular space occupied by smooth endoplasmic reticulum (SER) membranes] and lipid-droplet compartment, as well as the surface area of mitochondrial cristae and SER tubules, were increased in relation to the duration of ACTH pretreatment, and showed a highly significant positive linear correlation with both basal and stimulated corticosterone production. The acute exposure of isolated cells to ACTH provoked a striking lipid-droplet depletion, the extent of which was linearly and positively correlated with stimulated corticosterone secretion. The hypertrophy of the mitochondrial compartment and SER are interpreted as the morphological counterpart of the enhanced steroidogenic capacity of inner adrenocortical cells, inasmuch as the enzymes of steroid synthesis are located in these two organelles, and it is well known that chronic ACTH exposure stimulates the de novo synthesis of many of them in vivo. The rise in the number of lipid droplets, in which cholesterol is stored, is interpreted as being due to the fact that, under chronic ACTH treatment, the processes leading to cholesterol accumulation in adrenocortical cells (exogenous uptake and endogenous synthesis) exceed those of its utilization in basal steroid secretion. Cholesterol accumulated in lipid droplets as a reserve material may be rapidly utilized after acute ACTH exposure to meet the needs of the enhanced steroidogenic capacity of adrenocortical cells.     

Detection and discrimination between ochratoxin producer and non-producer strains of <Emphasis Type="Italic">Penicillium nordicum</Emphasis> on a ham-based medium using an electronic nose

The aim of this work was to evaluate the potential use of qualitative volatile patterns produced by Penicillium nordicum to discriminate between ochratoxin A (OTA) producers and non-producer strains on a ham-based medium. Experiments were carried out on a 3% ham medium at two water activities (a_w ; 0.995, 0.95) inoculated with P. nordicum spores and incubated at 25°C for up to 14 days. Growing colonies were sampled after 1, 2, 3, 7 and 14 days, placed in 30-ml vials, sealed and the head space analysed using a hybrid sensor electronic nose device. The effect of environmental conditions on growth and OTA production was evaluated based on the qualitative response. However, after 7 days, it was possible to discriminate between strains grown at 0.995 a_w, and after 14 days, the OTA producer and non-producer strain and the controls could be discriminated at both a_w levels. This study suggests that volatile patterns produced by P. nordicum strains may differ and be used to predict the presence of toxigenic contaminants in ham. This approach could be utilised in ham production as part of a quality assurance system for preventing OTA contamination.     

The different cleavage DNA sequence specificity explains the camptothecin resistance of the human topoisomerase I Glu418Lys mutant

Yeast cells expressing the Glu418Lys human topoisomerase I mutant display a camptothecin resistance that slowly decreases as a function of time. Molecular characterization of the single steps of the catalytic cycle of the purified mutant indicates that it has a relaxation activity identical to the wild-type protein but a different DNA sequence specificity for the cleavage sites when compared to the wild-type enzyme, as assayed on several substrates. In particular the mutant has a low specificity for CPT sensitive cleavable sites. In fact, the mutant has, at variance of the wild-type enzyme, a reduced preference for cleavage sites having a thymine base in position −1 of the scissile strand. This preference, together with the strict requirement for a thymine base in position −1 for an efficient camptothecin binding, explains the temporary camptothecin resistance of the yeast cell expressing the mutant and points out the importance of the DNA sequence in the binding of the camptothecin drug.