398 research outputs found
Repercussions of \u3ci\u3eCrawford v. Washington\u3c/i\u3e: A Child\u27s Statement to a Washington State Child Protective Services Worker May Be Inadmissible
Before the landmark United States Supreme Court case of Crawford v. Washington, Washington State courts often admitted statements of unavailable alleged child abuse victims through the hearsay testimony of Washington State Child Protective Services (CPS) workers. In Crawford, the U.S. Supreme Court announced a new testimonial standard for the admissibility of out-of-court statements. The Court held that the Confrontation Clause of the Sixth Amendment bars testimonial out-of-court statements unless the declarant is unavailable and the defendant had a prior opportunity to cross-examine the declarant. The Court did not clearly define the term testimonial, which left the matter open to interpretation by lower courts. The Crawford decision calls into question the continued admissibility of an unavailable child\u27s statement to a CPS worker. This Comment argues that Washington State courts should determine whether a child\u27s statement to a CPS worker is testimonial by analyzing whether the statement is formal and whether the child gave the statement in connection with a government investigation. The language in Crawford and case law from other jurisdictions support this fact-specific inquiry. Therefore, statements to CPS workers that Washington State courts most likely would have admitted before Crawford may now be testimonial and thus inadmissible at trial unless the defendant had a prior opportunity to cross-examine the child
The recognition of infection in the brain: toll-like receptor expression and innate immune responses to virus and prion infection
The mechanisms that mediate innate recognition of infections in the immunospecialised
environment of the central nervous system (CNS) have not been characterised. This thesis
explores the capability of the CNS to detect infections and activate immune responses. The
majority of CNS neurones are post-mitotic and cannot be replaced if lost or damaged.
Consequently, the resting CNS is devoid of most immune processes, although substantial
inflammatory responses can be initiated by specialised glial cells. The innate immune system
recognises conserved molecular patterns on microorganisms by a set of pattern recognition
receptors which include the Toll-like Receptors (TLR). A growing consensus suggests they
are key to the initiation of innate immune responses. Cellular expression of TLR imparts the
ability to detect infection and determine pathogen type. A multitude of TLRs have now been
cloned, although their function and expression patterns have not been described in the CNS.
This thesis aims to explore whether cells of the CNS express TLRs and whether they are
capable of responding to different stimuli. To explore gene expression a novel custom
microarray was designed, developed and validated to assay the expression of selected gene
transcripts involved in innate immune responses. These included a multitude of pattern
precognition receptors, in addition to transcripts associated with stress responses and a
variety of cytokine, chemokine and interferon (IFN) transcripts. In addition, a highly
sensitive quantitative PCR technique was developed. Utilising both techniques this thesis
reports the first systematic analysis of TLR gene expression in the CNS.Gene transcript levels were first studied in glial cells at rest. Cells were stimulated with
bacterial lipopolysaccharide, or by infection with the neuroinvasive Semliki Forest virus
(SFV). Both microglia and astrocytes in culture expressed a multitude of TLRs that were
differentially modulated in a specific manner depending on the nature of the stimulus. The
expression of TLR suggests glial cells are capable of recognising a vast array of microbialassociated
molecules. Such a strategy may be an essential requirement for an organ mostly
devoid of recognisable immune processes.In vivo, the resting CNS exhibited extensive TLR expression with TLR 3 expressed at
exceptionally high levels, comparable to that of lymphoid tissue, but varying with mouse
strain. The data reported here show for the first time that TLRs in the brain are upregulated
during viral encephalitis. Furthermore, this response was appropriate to the pathogen, with
selective up-regulation of TLRs that sense viral infection. Intracerebral inoculation with
either SFV or rabies virus initiated substantial upregulation of TLR 2, 3 and 9. Type-I IFN
independent mechanisms mediated the up-regulation of TLR 2 following SFV infection,
whilst for the two TLRs that mediate recognition of viral nucleic acids, TLR 3 and TLR 9,
upregulation of gene expression was dependent upon and proportional to the type-I IFN
response. It is likely that by up-regulating TLR 3 and 9, type-I IFN acts to increase the
sensitivity of cells in the vicinity of virally infected cells. In this hypothesis, basal levels of
TLR detect viral RNA and induce type-I IFN synthesis. This IFN acts in both an autocrine
and paracrine way to up-regulate a number of genes including TLR itself. In this way cells in
the vicinity of virally infected cells have their virus sensing mechanisms upregulated. This
parallels events with protein kinase R, another interferon inducible activator of innate
cellular defences.Transmissible spongiform encephalopathies are a group of diseases characterised by
chronic neurodegeneration and glial cell activation. This thesis demonstrates that the CNS
significantly upregulated several TLRs, and in the case of TLR 2, by 10-fold towards
terminal disease. This response further describes the apparent non-productive innate
immune activation of these cells during these diseases. In summary, the finding that the
brain has the ability via TLR expression to detect infection and discern its type provides an
important contribution to understanding pathological processes in this organ
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Conserved genomic organisation of Group B Sox genes in insects.
BACKGROUND: Sox domain containing genes are important metazoan transcriptional regulators implicated in a wide rage of developmental processes. The vertebrate B subgroup contains the Sox1, Sox2 and Sox3 genes that have early functions in neural development. Previous studies show that Drosophila Group B genes have been functionally conserved since they play essential roles in early neural specification and mutations in the Drosophila Dichaete and SoxN genes can be rescued with mammalian Sox genes. Despite their importance, the extent and organisation of the Group B family in Drosophila has not been fully characterised, an important step in using Drosophila to examine conserved aspects of Group B Sox gene function. RESULTS: We have used the directed cDNA sequencing along with the output from the publicly-available genome sequencing projects to examine the structure of Group B Sox domain genes in Drosophila melanogaster, Drosophila pseudoobscura, Anopheles gambiae and Apis mellifora. All of the insect genomes contain four genes encoding Group B proteins, two of which are intronless, as is the case with vertebrate group B genes. As has been previously reported and unusually for Group B genes, two of the insect group B genes, Sox21a and Sox21b, contain introns within their DNA-binding domains. We find that the highly unusual multi-exon structure of the Sox21b gene is common to the insects. In addition, we find that three of the group B Sox genes are organised in a linked cluster in the insect genomes. By in situ hybridisation we show that the pattern of expression of each of the four group B genes during embryogenesis is conserved between D. melanogaster and D. pseudoobscura. CONCLUSION: The DNA-binding domain sequences and genomic organisation of the group B genes have been conserved over 300 My of evolution since the last common ancestor of the Hymenoptera and the Diptera. Our analysis suggests insects have two Group B1 genes, SoxN and Dichaete, and two Group B2 genes. The genomic organisation of Dichaete and another two Group B genes in a cluster, suggests they may be under concerted regulatory control. Our analysis suggests a simple model for the evolution of group B Sox genes in insects that differs from the proposed evolution of vertebrate Group B genes.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
Objective and subjective comprehension of jury instructions in criminal trials
It would seem important that jury instructions are clear and comprehensible to jurors if they are to effectively carry out their responsibility in criminal trials. Research suggests, however, that jurors may not fully understand instructions despite reporting high levels of comprehension. The current study (N = 33) surveyed jurors who had recently served on a jury to assess their level of comprehension and the factors that contributed to their decisions. It was found that a substantial proportion of jurors were mistaken about directions relating to beyond reasonable doubt and burden of proof. It also was found that higher levels of self-reported comprehension were associated with self-reported reliance on additional factors to arrive at a decision, and a more positive evaluation of the prosecutions' case. Overall, although jurors report that they understand directions, they do not appear to use those directions in arriving at a decision. Subjective comprehension appears to be an important factor in understanding the effect of directions on jurors
The Selective Use of Rape-Victim Stereotypes to Protect Culturally Similar Perpetrators
This is the author accepted manuscript. The final version is available from Sage Publications via the DOI in this record.  Powerful stereotypes exist about how female rape victims should act. For example, victims are expected to physically resist their attacker and immediately report their assault. In reality, some victims are too shocked to physically resist or too traumatized to immediately go to police. Nevertheless, counterstereotypic-victim behavior can undermine fair prosecution outcomes, especially for acquaintance-rape victims. In the current research, we examined the influence of perceivers’ cultural similarity to the perpetrator, and the stereotypicality of rape-victim behaviour, on victim and perpetrator blame, punishment severity, and guilt likelihood. We varied an acquaintance-rape scenario, to present stereotypical/counterstereotypical rape-victim behaviour, and the cultural similarity/dissimilarity of perpetrators to participants, who were White-Australian women and men, aged between 18 and 74 (N = 237). In the victim-stereotypic condition, reactions did not vary as a function of perpetrator-cultural similarity. However, in the counterstereotypic-victim condition, culturally similar (compared to culturally dissimilar) perpetrators were considered less guilty and less deserving of punishment. Moderated mediation indicated that the greater leniency shown towards culturally similar perpetrators was explained by increases in victim blame and decreases in perpetrator blame. To decrease bias when prosecuting rape perpetrators, we recommend challenging the selective use of counterstereotypic-victim behaviour to defend culturally similar perpetrators.Australian Research Counci
Microarray analyses demonstrate the involvement of type i interferons in psoriasiform pathology development in D6-deficient mice
The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes
Judgments of sexual assault: the impact of complainant emotional demeanor, gender and victim stereotypes
The sexual assault victim "who comes to the attention of the authorities has her victimization measured against the current rape mythologies" (R v. Seaboyer, 1991). This is particularly troubling given that lay beliefs regarding the crime of sexual assault are at odds with the data documenting the circumstances surrounding actual rape. Research has consistently demonstrated that lay people (hence, jurors) will question the validity of a sexual assault claim and judge the victim more harshly, if the circumstances surrounding the assault and/or the characteristics and actions of the sexual assault complainant do not comport with people's expectations about the event. In this paper we report the results of a juror simulation that examines the impact of victim's postassault emotional demeanor on judgments, in the context of independent manipulations of gender stereotypicality and victim stereotypicality. Results revealed that the complainant's emotional display had a powerful impact on participants' judgments, with the claim viewed as more valid when the complainant was portrayed as tearful/upset as opposed to calm/controlled, but only when the complainant was portrayed as gender stereotypic
MicroRNA-146 and cell trauma down-regulate expression of the psoriasis-associated atypical chemokine receptor ACKR2
Chemokines are the principal regulators of leukocyte migration and are essential for initiation and maintenance of inflammation. Atypical chemokine receptor 2 (ACKR2) binds and scavenges proinflammatory CC-chemokines, regulates cutaneous T-cell positioning, and limits the spread of inflammation in vivo. Altered ACKR2 function has been implicated in several inflammatory disorders, including psoriasis, a common and debilitating T-cell–driven disorder characterized by thick erythematous skin plaques. ACKR2 expression is abnormal in psoriatic skin, with decreased expression correlating with recruitment of T-cells into the epidermis and increased inflammation. However, the molecular mechanisms that govern ACKR2 expression are not known. Here, we identified specific psoriasis-associated microRNAs (miRs) that bind ACKR2, inhibit its expression, and are active in primary cultures of human cutaneous cells. Using both in silico and in vitro approaches, we show that miR-146b and miR-10b directly bind the ACKR2 3′-UTR and reduce expression of ACKR2 transcripts and protein in keratinocytes and lymphatic endothelial cells, respectively. Moreover, we demonstrate that ACKR2 expression is further down-regulated upon cell trauma, an important trigger for the development of new plaques in many psoriasis patients (the Koebner phenomenon). We found that tensile cell stress leads to rapid ACKR2 down-regulation and concurrent miR-146b up-regulation. Together, we provide, for the first time, evidence for epigenetic regulation of an atypical chemokine receptor. We propose a mechanism by which cell trauma and miRs coordinately exacerbate inflammation via down-regulation of ACKR2 expression and provide a putative mechanistic explanation for the Koebner phenomenon in psoriasis
On being loud and proud: Non-conformity and counter-conformity to group norms
Most experiments on conformity have been conducted in relation to judgments of physical reality; surprisingly few papers have experimentally examined the influence of group norms on social issues with a moral component. In response to this, we told students that they were either in a minority or in a majority relative to their university group on their attitudes toward recognition of gay couples in law (Experiment 1: N=205) and a government apology to Aborigines (Experiment 2: N=110). We found that participants who had a weak moral basis for their attitude, or who perceived high societal support for their attitude, were more willing to privately act in line with their attitude when they had group support than when they did not. In contrast, those who had a strong moral basis for their attitude, or who perceived low societal support for their attitude, showed non-conformity on private behaviors and counter-conformity on public behaviors. Incidences of non-conformity and counter-conformity are discussed with reference to the traditional theoretical emphasis on assimilation to group norms
The N-terminal region of the atypical chemokine receptor ACKR2 is a key determinant of ligand binding
The atypical chemokine receptor, ACKR2 is a pivotal regulator of chemokine-driven inflammatory responses and works by binding, internalizing, and degrading inflammatory CC-chemokines. ACKR2 displays promiscuity of ligand binding and is capable of interacting with up to 14 different inflammatory CC-chemokines. Despite its prominent biological role, little is known about the structure/function relationship within ACKR2, which regulates ligand binding. Here we demonstrate that a conserved tyrosine motif at the N terminus of ACKR2 is essential for ligand binding, internalization, and scavenging. In addition we demonstrate that sulfation of this motif contributes to ligand internalization. Furthermore, a peptide derived from this region is capable of binding inflammatory chemokines and inhibits their interaction with their cognate signaling receptors. Importantly, the peptide is only active in the sulfated form, further confirming the importance of the sulfated tyrosines for function. Finally, we demonstrate that the bacterial protease, staphopain A, can cleave the N terminus of ACKR2 and suppress its ligand internalization activity. Overall, these results shed new light on the nature of the structural motifs in ACKR2 that are responsible for ligand binding. The study also highlights ACKR2-derived N-terminal peptides as being of potential therapeutic significance
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