α-Elapitoxin-Aa2a, a long-chain snake α-neurotoxin with potent actions on muscle (α1)<inf>2</inf>βγδ nicotinic receptors, lacks the classical high affinity for neuronal α7 nicotinic receptors

In contrast to all classical long-chain α-neurotoxins possessing the critical fifth disulfide bond, α-elapitoxin-Aa2a (α-EPTX-Aa2a), a novel long-chain α-neurotoxin from the common death adder Acanthophis antarcticus, lacks affinity for neuronal α7-type nicotinic acetylcholine receptors (nAChRs) α-EPTX-Aa2a (8850 Da; 0.1-1 μM) caused a concentration-dependent inhibition of indirect twitches, and blocked contractures to cholinergic agonists in the isolated chick biventer cervicis nerve-muscle preparation, consistent with a postsynaptic curaremimetic mode of action. α-EPTX-Aa2a (1-10 nM) produced a potent pseudo-irreversible antagonism of chick muscle nAChRs, with an estimated pA2 value of 8.311 ± 0.031, which was not reversed by monovalent death adder antivenom. This is only 2.5-fold less potent than the prototypical long-chain α-neurotoxin, α-bungarotoxin. In contrast, α-EPTX-Aa2a produced complete, but weak, inhibition of 125I-α-bungarotoxin binding to rat hippocampal α7 nAChRs (pKI = 3.670), despite high sequence homology and similar mass to a wide range of long-chain α-neurotoxins. The mostly likely cause for the loss of α7 binding affinity is a leucine substitution, in loop II of α-EPTX-Aa2a, for the highly conserved Arg33 in long-chain α-neurotoxins. Arg 33 has been shown to be critical for both neuronal and muscle activity. Despite this substitution, α-EPTX-Aa2a retains high affinity for muscle (α1)2βγδ nAChRs. This is probably as a result of an Arg29 residue, previously shown to be critical for muscle (α1)2βγδ nAChR affinity, and highly conserved across all short-chain, but not long-chain, α-neurotoxins. α-EPTX-Aa2a therefore represents a novel atypical long-chain α-neurotoxin that includes a fifth disulfide but exhibits differential affinity for nAChR subtypes. Copyright © 2010 Published by Elsevier Inc. All rights reserved

Community Policing: Broken Windows, Community Building, and Satisfaction with the Police

The concept of community policing dominates the law enforcement profession today. One would be hard pressed to find an advertisement for a police chief’s position that does not require a thorough understanding of this method of policing. Like the Kansas City preventive patrol experiment and the Rand report on the criminal investigation process, the call for community policing has led to dramatic changes in the way that police carry out their responsibilities. In spite of its popularity, there have been a number of challenges to community policing from social scientists who are particularly concerned about the ‘broken windows’ model of policing. These challenges have not been received well by the law enforcement community, which argues that sociologists are wedded to the idea that crime is caused by the structural features of capitalist society, including economic injustice, racism, and poverty. The purpose of this article is to bridge the gap between these two positions. Yes, there is a place for community policing, and, yes, social problems do contribute to crime. The article starts by reviewing the development of community policing in the United States. An analysis of the theoretical constructs that support community policing then follows. Finally, we argue that there is sound theoretical evidence to support community policing, particularly those programmes that improve citizen satisfaction with the manner in which police carry out their responsibilities

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

A Conflict Model for Strategists and Managers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67210/2/10.1177_000276427201500604.pd

Political Radicalization as a Communication Process

Based on data taken from 412 adult education students in Montreal, Quebec, Canada, this research attempts to show that attitudes toward French Canadian Separatism by the sample members can be accounted for by differentiaf communication processes. Results show that attitudes held by sample members are well explained (R2 = .64) by a weighted average of the information they received from interpersonal and media sources. The resultant attitude shows substantial effects on behaviors related to separatism for the same respondents.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67215/2/10.1177_009365027400100301.pd

Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome

The ecology of outdoor rape: The case of Stockholm, Sweden

The objective of this article is to report the results of an ecological study into the geography of rape in Stockholm, Sweden, using small area data. In order to test the importance of factors indicating opportunity, accessibility and anonymity to the understanding of the geography of rape, a two-stage modelling approach is implemented. First, the overall risk factors associated with the occurrence of rape are identified using a standard Poisson regression, then a local analysis using profile regression is performed. Findings from the whole-map analysis show that accessibility, opportunity and anonymity are all, to different degrees, important in explaining the overall geography of rape - examples of these risk factors are the presence of subway stations or whether a basområde is close to the city centre. The local analysis reveals two groupings of high risk of rape areas associated with a variety of risk factors: city centre areas with a concentration of alcohol outlets, high residential population turnover and high counts of robbery; and poor suburban areas with schools and large female residential populations where subway stations are located and where people express a high fear of crime. The article concludes by reflecting upon the importance of these results for future research as well as indicating the implications of these results for policy