Asynchronous snowdrift game with synergistic effect as a model of cooperation

The snowdrift (or chicken) game emerges as a new paradigm inthe study of nonkin cooperation in animals. Many situations,for example, cooperative hunting, group foraging, territorialdefense, predator watching, or parental care, can be adequatelydescribed as a snowdrift game. In this paper, we investigatethe asynchronous version of the game in which, contrary to therather unrealistic assumption of simultaneous moves, one ofthe players acts first and the other responds by knowing itsdecision. Players are assigned to be first or second moversrandomly and with the same probability. We found that both asynergistic effect of cooperation (i.e., cooperative effortis better than the sum of the individual efforts) and populationstructure (low dispersal, spatial confinement, or group formation)are crucial for mutual cooperation to emerge. Otherwise, onlyone of the players will carry the burden of cooperation.     

Synthesis and Immunological Evaluation of M Protein Targeted Tetra-Valent and Tri-Valent Group A Streptococcal Vaccine Candidates Based on the Lipid-Core Peptide System

Group A streptococcus (GAS) is responsible for causing many clinical complications including the relatively benign streptococcal pharyngitis and impetigo. However, if left untreated, these conditions may lead to more severe diseases such as rheumatic fever (RF) and rheumatic heart disease (RHD). These diseases exhibit high morbidity and mortality, particularly in developing countries and in indigenous populations of affluent countries. As RF and RHD only ever occur following GAS infection, a vaccine offers promise for their prevention. As such, we have investigated the use of the lipid-core peptide (LCP) system for the development of multi-valent prophylactic GAS vaccines. The current study has investigated the capacity of this system to adjuvant up to four different GAS peptide epitopes. Presented are the synthesis and immunological assessment of tetra-valent and tri-valent GAS LCP systems. We demonstrated their capacity to elicit systemic IgG antibody responses in B10.BR mice to all GAS peptide epitopes. The data also showed that the LCP systems were self-adjuvanting. These findings are particularly encouraging for the development of multi-valent LCP-based GAS vaccines.     

Expression of glucocorticoid receptor isoforms in human adrenocortical adenomas

Introduction

Glucocorticoid receptor (GR) is expressed in the normal human adrenal gland, however, no study has been performed to evaluate the separate expression of α- and β-isoforms (GRα and GRβ) in normal human adrenals and in adrenocortical adenomas.

Experimental

GRα and GRβ mRNA expression was examined by quantitative real-time PCR in 31 adrenal tissues including 19 non-functioning adenomas (NFA), 6 cortisol-producing adenomas (CPA) and 6 normal adrenocortical tissues. In addition, the presence and cellular localization of GRα and GRβ proteins in adrenal tissues were studied by immunohistochemistry.

Results

Compared to normal adrenocortical tissues, both GRα and GRβ mRNAs were significantly increased in CPA but not in NFA. Using anti-GRα antibody a strong nuclear staining was observed in NFA and CPA, and a less remarkable immunoreactivity was detected in some nuclei of normal adrenocortical cells. GRβ immunostaining was absent in normal adrenal tissues and NFA, while a strong cytoplasmic and nuclear immunoreaction was found in CPA.

Conclusions

Altered expression of GRα and GRβ in CPA raises their possible role in the pathophysiology of these adrenal tumors, although further studies are needed to elucidate the potential significance of these findings.     

Are gobiid fish more susceptible to predation if parasitized by Eustrongylides excisus? An answer from robbed snakes

Aspects of the predator–prey relationship between dice snake, Natrix tessellata and gobiid fish infected with Eustrongylides excisus were studied in Lake Sinoe, Romania. A population of snakes residing here shows a high prevalence of subcutaneous larvae of this nematode. The hypothesis of the altered motility in infected fish leading to increased depredation by snakes was tested by comparing gobiids collected from dice snakes with gobiids caught via electrofishing. Out of a total of seven identified gobiid species, three were used for analysis: syrman goby Neogobius syrman, mushroom goby Neogobius eurycephalus, and round goby Neogobius melanostomus. No significant differences in prevalence and intensity of E. excisus infection were found between fish caught by snakes and those obtained by electrofishing. However, significantly higher abundance of E. excisus larvae in fish caught by snakes was reported. These findings suggest limited influence of the presence of E. excisus larvae in studied gobiids regarding their susceptibility to predation by dice snakes.     

Reduction of reperfusion‐induced ventricular fibrillation and infarct size via heme oxygenase‐1 overexpression in isolated mouse hearts

Heme oxygenase‐1 (HO‐1), also known as heat shock protein 32 (hsp‐32) is a stress‐induced cytoprotective protein. The present investigation evaluated the capacity of HO‐1 to reduce the incidence of reperfusion‐induced ventricular fibrillation (VF) and infarct size. HO‐1 transgenic (Tg) mice were generated using a rat HO‐1 genomic transgene. Isolated mouse hearts obtained from Tg and non‐transgenic (NTg) groups were exposed to 20 min. of global ischemia and 120 min. of reperfusion. Epicardial electrocardiogram was recorded to monitor the incidence of reperfusion‐induced VF and at the end of the reperfusion period, detection of HO‐1 by immunohistochemistry and measurement of infarct size using the tetrazolium chloride method were carried out. Results shown here provide additional support for cardioprotective effects of HO‐1 as demonstrated by the reduced infarct size. Moreover, overexpression of the HO‐1 efficiently reduced the incidence of ischemia/reperfusion induced VF in HO‐1 Tg mice.     

Development of lipid-core-peptide (LCP) based vaccines for the prevention of group A streptococcal (GAS) infection

Traditional vaccines consisting of whole attenuated micro-organisms, or microbial components administered with adjuvant, have been demonstrated as one of the most cost-effective and successful public health interventions. Their use in large scale immunisation programs has lead to the eradication of smallpox, reduced morbidity and mortality from many once common diseases, and reduced strain on health services. However, problems associated with these vaccines including risk of infection, adverse effects, and the requirement for refrigerated transport and storage have led to the investigation of alternative vaccine technologies. Peptide vaccines, consisting of either whole proteins or individual peptide epitopes, have attracted much interest, as they may be synthesised to high purity and induce highly specific immune responses. However, problems including difficulties stimulating long lasting immunity, and population MHC diversity necessitating multiepitopic vaccines and/or HLA tissue typing of patients complicate their development. Furthermore, toxic adjuvants are necessary to render them immunogenic, and as such non-toxic human-compatible adjuvants need to be developed. Lipidation has been demonstrated as a human compatible adjuvant for peptide vaccines. The lipid-core-peptide (LCP) system, incorporating lipid adjuvant, carrier, and peptide epitopes, exhibits promise as a lipid-based peptide vaccine adjuvant. The studies reviewed herein investigate the use of the LCP system for developing vaccines to protect against group A streptococcal (GAS) infection. The studies demonstrate that LCP-based GAS vaccines are capable of inducing high-titres of antigen specific IgG antibodies. Furthermore, mice immunised with an LCP-based GAS vaccine were protected against challenge with 8830 strain GAS.     

Towards synthetic vaccines built on carbohydrate cores

Summary Lipophilic polyfunctional carbohydrate core/templates have been designed and developed for drug/vaccine delivery. Three carbohydrate-based templates containing four protectedN-terminal arms were synthesised from glucose and galactose. Methyl α-D-glucopyranoside was converted to two derivatives bearing a carboxylic acid handle for attachment to solid supports, spacer arms of differing hydrophilicity, and phthaloyl-protected amino groups suitable for peptide chain extension. β-D-Galactopyranosyl azide was converted to a template bearing a carboxylic acid handle and four BOC-protected amines. All the templates were found to be suitable for attachment to solid supports and subsequent cleavage from resins, using either BOC-or FMOC-methodologies.     

Distinguishing Between GABAA Receptors Responsible for Tonic and Phasic Conductances

Cell-to-cell communication in the mammalian nervous system does not solely involve direct synaptic transmission. There is considerable evidence for a type of communication between neurons through chemical means that lies somewhere between the rapid synaptic information transfer and the relatively non-specific neuroendocrine secretion. Here I review some of the experimental evidence accumulated for the GABA system indicating that GABA_A receptor-gated Cl-channels localized at synapses differ significantly from those found extrasynaptically. These two types of GABA_A receptor are involved in generating distinctly different conductances. Thus, the development and search for pharmacological agents specifically aimed at selectively altering synaptic and extrasynaptic GABA_A conductances is within reach, and is expected to provide novel insights into the regulation of neuronal excitability.