Chemotactic activity of pertussis toxin on murine lymphocytes. Its potential role on lymphocyte accumulation in the lung

Abstract The effects of pertussis toxin on lymphocyte migration were studied in vitro. In this study pertussis toxin significantly stimulated lymphocyte migration at concentrations of 0.1 and 1 μg ml⁻¹ using a microchamber and the leading-front method. Checkerboard analysis demonstrated that pertussis toxin causes directed migration of lymphocytes (chemotaxis). Heat-treatment of pertussis toxin abolished its capacity to cause this migration. When murine lymphocytes were preincubated with different concentrations of pertussis toxin, an inhibition of chemotaxis at the dosages of 0.1 and 1 μg ml⁻¹ was observed. On the other hand, lymphocytes derived from mice treated with pertussis toxin were not inhibited after subsequent exposure to pertussis toxin in vitro. Since lymphocyte accumulation in the lungs of mice treated with pertussis toxin has been well domenstrated, the results of our study could suggest a chemotactic activity of pertussis toxin in determining accumulation of lymphocytes in this organ.     

Surgical Stress Delays Prostate Involution in Mice

Androgens control growth of prostate epithelial cells and androgen deprivation induces apoptosis, leading to prostate involution. We investigated the effects of surgical stress on prostate involution induced by androgen ablation and determined the underlying mechanisms. Androgen ablation in mice was induced by surgical castration and administration of the anti-androgenic drugs bicalutamide and MDV3100. Surgical stress was induced by sham castration under isoflurane anesthesia. Surgical stress delayed apoptosis and prostate involution induced by anti-androgenic drugs. These effects of stress were prevented by administering the selective beta2-adrenoreceptor antagonist ICI118,551 and were also blocked in BAD^3SA/WT mice expressing phosphorylation-deficient mutant BAD3SA. These results indicate that apoptosis and prostate involution in response to androgen ablation therapy could be delayed by surgical stress via the beta2-adrenoreceptor/BAD signaling pathway. Thus, surgery could interfere with androgen ablation therapy, whereas administration of beta2-adrenoreceptor antagonists may enhance its efficacy.     

Morpho-physiological responses of sugar beet (Beta vulgaris L.) genotypes to drought stress

The identification of morpho-physiological traits related to drought tolerance and high yield potential is a challenge when selecting sugar beet genotypes with greater tolerance to water stress. In this paper, root morphological parameters, antioxidant systems, leaf relative water content (RWC) and H⁺-ATPase activity as key morpho-physiological traits involved in drought tolerance/susceptibility of sugar beet were studied. Genotypes showing a different drought tolerance index (DTI) but a similar yield potential, under moderate (?0.6 Mpa) and severe (?1.2 MPa) water stress, were selected and their morpho-physiological traits were investigated. The results showed a wide genetic variation in morpho-physiological parameters which demonstrated the different adaptive strategies under moderate and severe drought conditions in sugar beet. In particular, an efficient antioxidant system and redox signalling made some sugar beet genotypes more tolerant to drought stress. The alternative strategy of other genotypes was the reduction of root tissue density, which produced a less dense root system improving the axial hydraulic conductivity. These results could be considered as interesting challenge for a better understanding of the drought tolerance mechanisms in sugar beet.     

A conserved ClpP‐like protease involved in spore outgrowth in Bacillus subtilis

Germination and outgrowth of endospores of the Gram‐positive bacterium Bacillus subtilis involves the degradation and conversion to free amino acids of abundant proteins located in the spore core known as small acid‐soluble proteins (SASP). This degradation is mediated primarily by the germination protease Gpr. Here we show that YmfB, a distant homologue of ClpP serine proteases that is highly conserved among endospore‐forming bacteria, contributes to SASP degradation but that its function is normally masked by Gpr. Spores from a ymfB gpr double mutant were more delayed in spore outgrowth and more impaired in SASP degradation than were spores from a gpr single mutant. The activity of YmfB relied on three putative active‐site residues as well as on the product of a small gene ylzJ located immediately downstream of, and overlapping with, ymfB. We propose that YmfB is an orphan ClpP protease that is dedicated to the degradation of a specialized family of small protein substrates.     

The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer

Introduction

Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease.

Methods

We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week). Tumor growth was monitored by in vivo bioluminescent imaging.

Results

KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls.

Conclusions

KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.     

Evaluation of LiF:Mg,Ti (TLD-100) for Intraoperative Electron Radiation Therapy Quality Assurance

Background

Purpose of the present work was to investigate thermoluminescent dosimeters (TLDs) response to intraoperative electron radiation therapy (IOERT) beams. In an IOERT treatment, a large single radiation dose is delivered with a high dose-per-pulse electron beam (2–12 cGy/pulse) during surgery. To verify and to record the delivered dose, in vivo dosimetry is a mandatory procedure for quality assurance. The TLDs feature many advantages such as a small detector size and close tissue equivalence that make them attractive for IOERT as in vivo dosimeters.

Methods

LiF:Mg,Ti dosimeters (TLD-100) were irradiated with different IOERT electron beam energies (5, 7 and 9 MeV) and with a 6 MV conventional photon beam. For each energy, the TLDs were irradiated in the dose range of 0–10 Gy in step of 2Gy. Regression analysis was performed to establish the response variation of thermoluminescent signals with dose and energy.

Results

The TLD-100 dose-response curves were obtained. In the dose range of 0–10 Gy, the calibration curve was confirmed to be linear for the conventional photon beam. In the same dose region, the quadratic model performs better than the linear model when high dose-per-pulse electron beams were used (F test; p<0.05).

Conclusions

This study demonstrates that the TLD dose response, for doses ≤10Gy, has a parabolic behavior in high dose-per-pulse electron beams. TLD-100 can be useful detectors for IOERT patient dosimetry if a proper calibration is provided.     

Emergence of Leadership in a Group of Autonomous Robots

In this paper we examine the factors contributing to the emergence of leadership in a group, and we explore the relationship between the role of the leader and the behavioural capabilities of other individuals. We use a simulation technique where a group of foraging robots must coordinate to choose between two identical food zones in order to forage collectively. Behavioural and quantitative analysis indicate that a form of leadership emerges, and that groups with a leader are more effective than groups without. Moreover, we show that the most skilled individuals in a group tend to be the ones that assume a leadership role, supporting biological findings. Further analysis reveals the emergence of different “styles” of leadership (active and passive).     

Suitable Environmental Ranges for Potential Coral Reef Habitats in the Tropical Ocean

Coral reefs are found within a limited range of environmental conditions or tolerance limits. Estimating these limits is a critical prerequisite for understanding the impacts of climate change on the biogeography of coral reefs. Here we used the diagnostic model ReefHab to determine the current environmental tolerance limits for coral reefs and the global distribution of potential coral reef habitats as a function of six factors: temperature, salinity, nitrate, phosphate, aragonite saturation state, and light. To determine these tolerance limits, we extracted maximum and minimum values of all environmental variables in corresponding locations where coral reefs are present. We found that the global, annually averaged tolerance limits for coral reefs are 21.7—29.6 °C for temperature, 28.7—40.4 psu for salinity, 4.51 μmol L^-1 for nitrate, 0.63 μmol L^-1 for phosphate, and 2.82 for aragonite saturation state. The averaged minimum light intensity in coral reefs is 450 μmol photons m^-2 s^-1. The global area of potential reef habitats calculated by the model is 330.5 × 10³ km². Compared with previous studies, the tolerance limits for temperature, salinity, and nutrients have not changed much, whereas the minimum value of aragonite saturation in coral reef waters has decreased from 3.28 to 2.82. The potential reef habitat area calculated with ReefHab is about 121×10³ km² larger than the area estimated from the charted reefs, suggesting that the growth potential of coral reefs is higher than currently observed.