Impairments of hippocampal synaptic plasticity induced by aggregated beta-amyloid (25-35) are dependent on stimulation-protocol and genetic background

The aggregation of beta-amyloid to plaques in the brain is one of the hallmarks of Alzheimer disease (AD). Numerous studies have tried to elucidate to what degree amyloid peptides play a role in the neurodegenerative developments seen in AD. While most studies report an effect of amyloid on neural activity and cognitive abilities of rodents, there have been many inconsistencies in the results. This study investigated to what degree the different genetic backgrounds affect the outcome of beta-amyloid fragment (25-35) on synaptic plasticity in vivo in the rat hippocampus. Two strains, Wistar and Lister hooded rats, were tested. In addition, the effects of a strong (600 stimuli) and a weak stimulation protocol (100 stimuli) on impairments of LTP were analysed. Furthermore, since the state of amyloid aggregation appears to play a role in the induction of toxic processes, it was tested by dual polarisation interferometry to what degree and at what speed beta-amyloid (25-35) can aggregate in vitro. It was found that 100 nmol beta-amyloid (25-35) injected icv did impair LTP in Wistar rats when using the weak but not the strong stimulation protocol (P <0.001). One-hundred nano mole of the reverse sequence amyloid (35-25) had no effect. LTP in Lister Hooded rats was not impaired by amyloid at any stimulation protocol. The aggregation studies showed that amyloid (25-35) aggregated within hours, while amyloid (35-25) did not. These results show that the genetic background and the stimulation protocol are important variables that greatly influence the experimental outcome. The fact that amyloid (25-35) aggregated quickly and showed neurophysiological effects, while amyloid (35-25) did not aggregate and did not show any effects indicates that the state of aggregation plays an important role in the physiological effects.

Background beliefs and evidence interpretation

In this paper we argue that it is often adaptive to use one’s background beliefs when interpreting information that, from a normative point of view, is incomplete. In both of the experiments reported here participants were presented with an item possessing two features and were asked to judge, in the light of some evidence concerning the features, to which of two categories it was more likely that the item belonged. It was found that when participants received evidence relevant to just one of these hypothesised categories (i.e. evidence that did not form a Bayesian likelihood ratio) they used their background beliefs to interpret this information. In Experiment 2, on the other hand, participants behaved in a broadly Bayesian manner when the evidence they received constituted a completed likelihood ratio. We discuss the circumstances under which participants, when making their judgements, consider the alternative hypothesis. We conclude with a discussion of the implications of our results for an understanding of hypothesis testing, belief revision, and categorisation.

‘Stakeholders’ views of legal and advice services for people admitted to psychiatric hospital’

This paper describes a study that used a mixed method approach to elicit the views of a range of stakeholders about experiences of compulsory admission to psychiatric hospital, and the use of the Mental Health Review Tribunal (MHRT). The paper begins with an introduction to the background of the study, one that took place in Northern Ireland, a region in the UK with its own mental health legislation and policy. A review of literature is then presented. This highlights some of the disadvantages that service users and carers face when dealing with professionals during and following compulsory admission to hospital. This section concludes with an overview of literature on the MHRT in the UK. A range of methods was used to gather data from the following stakeholders: five service user and carer focus group interviews (n = 44); interviews with four lawyers experienced in Tribunal work; an interview with a legal member of the Tribunal; a survey of solicitors who identified themselves as equipped to carry out Tribunal work; interviews with three managers of organisations that provided patient advocacy services; letters to hospital managers requesting information provided to patients and carers. The findings reveal a number of themes associated with these experiences of compulsory admission to hospital and subsequent use of the Tribunal. Service users and carers generally found it difficult to access relevant information about rights, information provided by hospital managers was uneven and lawyers were often not familiar with processes associated with compulsory admission. There was a range of views about the Tribunal. Most respondents felt that the Tribunal was necessary and mostly satisfactory in the way it carried out its functions, but stakeholders raised a number of issues. Carers in particular felt that they should be more involved in decision-making processes, whereas lawyers tended to be focused on more technical, legal issues. Problems of regrading prior to the Tribunal and in examining medical evidence were highlighted by lawyers. There was an appeal for better information and advice by service users and carers, and recognition of the need for better training and education for lawyers. The paper concludes with a brief discussion about current mental health law in the UK, arguing that, in this context, professionals should more proactively use information and advice that can enable service users and carers to defend their rights. Keywords: compulsory mental health; law; legal and advice services

Modulational instability of dust acoustic waves in dusty plasmas: Modulation obliqueness, background ion nonthermality, and dust charging effects

The oblique modulational instability of dust acoustic (DA) waves in an unmagnetized warm dusty plasma with nonthermal ions, taking into account dust grain charge variation (charging), is investigated. A nonlinear Schrodinger-type equation governing the slow modulation of the wave amplitude is derived. The effects of dust temperature, dust charge variation, ion deviation from Maxwellian equilibrium (nonthermality) and constituent species' concentration on the modulational instability of DA waves are examined. It is found that these parameters modify significantly the oblique modulational instability domain in the k-theta plane. Explicit expressions for the instability rate and threshold have been obtained in terms of the dispersion laws of the system. The possibility and conditions for the existence of different types of localized excitations are also discussed. The findings of this investigation may be useful in understanding the stable electrostatic wave packet acceleration mechanisms close to the Moon, and also enhances our knowledge on the occurrence of instability associated to pickup ions around unmagnetized bodies, such as comets, Mars, and Venus.

Somatic point mutations in mtDNA control region are influenced by genetic background and associated with healthy aging: a GEHA stud

Tissue specific somatic mutations occurring in the mtDNA control region have been proposed to provide a survival advantage. Data on twins and on relatives of long-lived subjects suggested that the occurrence/accumulation of these mutations may be genetically influenced. To further investigate control region somatic heteroplasmy in the elderly, we analyzed the segment surrounding the nt 150 position (previously reported as specific of Leukocytes) in various types of leukocytes obtained from 195 ultra-nonagenarians sib-pairs of Italian or Finnish origin collected in the frame of the GEHA Project. We found a significant correlation of the mtDNA control region heteroplasmy between sibs, confirming a genetic influence on this phenomenon. Furthermore, many subjects showed heteroplasmy due to mutations different from the C150T transition. In these cases heteroplasmy was correlated within sibpairs in Finnish and northern Italian samples, but not in southern Italians. This suggested that the genetic contribution to control region mutations may be population specific. Finally, we observed a possible correlation between heteroplasmy and Hand Grip strength, one of the best markers of physical performance and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNA somatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNA control region may represent a strategy for the age-related remodelling of organismal functions.