5-Methyl-2'-deoxycytidine in single-stranded DNA can act in cis to signal de novo DNA methylation.

Methylation of cytosine residues in DNA plays an important role in regulating gene expression during vertebrate embryonic development. Conversely, disruption of normal patterns of methylation is common in tumors and occurs early in progression of some human cancers. In vertebrates, it appears that the same DNA methyltransferase maintains preexisting patterns of methylation during DNA replication and carries out de novo methylation to create new methylation patterns. There are several indications that inherent signals in DNA structure can act in vivo to initiate or block de novo methylation in adjacent DNA regions. To identify sequences capable of enhancing de novo methylation of DNA in vitro, we designed a series of oligodeoxyribonucleotide substrates with substrate cytosine residues in different sequence contexts. We obtained evidence that some 5-methylcytosine residues in these single-stranded DNAs can stimulate de novo methylation of adjacent sites by murine DNA 5-cytosine methyltransferase as effectively as 5-methylcytosine residues in double-stranded DNA stimulate maintenance methylation. This suggests that double-stranded DNA may not be the primary natural substrate for de novo methylation and that looped single-stranded structures formed during the normal course of DNA replication or repair serve as "nucleation" sites for de novo methylation of adjacent DNA regions.

Prolactin-immunoglobulin G complexes from human serum act as costimulatory ligands causing proliferation of malignant B lymphocytes.

Several lines of evidence indicate that immunoglobulin-bound prolactin found in human serum is not a conventional complex between an anti-prolactin antibody and prolactin but a different type of association of prolactin with the Fab portion of IgG heavy chains. The complex of prolactin with IgG was purified from serum by anti-human prolactin affinity chromatography and was shown to contain close to 1 mole of N epsilon-(gamma-glutamyl)lysine crosslinks per mole of complex, a characteristic feature in structures crosslinked by transglutaminase. Interestingly, the complex caused a proliferation of cells from a subset of patients with chronic lymphocytic leukemia, while it was inactive in a cell proliferation prolactin bioassay. By contrast, human prolactin stimulated the proliferation of cells in the bioassay but had no effect on the complex-responsive cells from the patients. Competition studies with prolactin and free Fc fragment of IgG demonstrated a necessity for engaging both the prolactin and the immunoglobulin receptors for proliferation. More importantly, competition for the growth response by free prolactin and IgG suggests both possible reasons for the slow growth of this neoplasm as well as avenues for control of the disease.

Caught in the act: gas and stellar velocity dispersions in a fast Quenching compact star-forming galaxy at z ~ 1.7

We present Keck I MOSFIRE spectroscopy in the Y and H bands of GDN-8231, a massive, compact, star-forming galaxy at a redshift of z ~ 1.7. Its spectrum reveals both Hα and [Nii] emission lines and strong Balmer absorption lines. The Hα and Spitzer MIPS 24 μm fluxes are both weak, thus indicating a low star-formation rate of SFR≲5-10 M_⨀ yr−1. This, added to a relatively young age of ~700 Myr measured from the absorption lines, provides the first direct evidence for a distant galaxy being caught in the act of rapidly shutting down its star formation. Such quenching allows GDN-8231 to become a compact, quiescent galaxy, similar to three other galaxies in our sample, by z ~ 1.5. Moreover, the color profile of GDN-8231 shows a bluer center, consistent with the predictions of recent simulations for an early phase of inside-out quenching. Its line-of-sight velocity dispersion for the gas, σ_LOG^gas = 127 ± 32 km s^−1, is nearly 40% smaller than that of its stars, σ_LOG^* = 215 ± 35 km s^−1. High-resolution hydro-simulations of galaxies explain such apparently colder gas kinematics of up to a factor of ~1.5 with rotating disks being viewed at different inclinations and/or centrally concentrated star-forming regions. A clear prediction is that their compact, quiescent descendants preserve some remnant rotation from their star-forming progenitors.

Sub-Cellular Localization and Complex Formation by Aminoacyl-tRNA Synthetases in Cyanobacteria: Evidence for Interaction of Membrane-Anchored ValRS with ATP Synthase

tRNAs are charged with cognate amino acids by aminoacyl-tRNA synthetases (aaRSs) and subsequently delivered to the ribosome to be used as substrates for gene translation. Whether aminoacyl-tRNAs are channeled to the ribosome by transit within translational complexes that avoid their diffusion in the cytoplasm is a matter of intense investigation in organisms of the three domains of life. In the cyanobacterium Anabaena sp. PCC 7120, the valyl-tRNA synthetase (ValRS) is anchored to thylakoid membranes by means of the CAAD domain. We have investigated whether in this organism ValRS could act as a hub for the nucleation of a translational complex by attracting other aaRSs to the membranes. Out of the 20 aaRSs, only ValRS was found to localize in thylakoid membranes whereas the other enzymes occupied the soluble portion of the cytoplasm. To investigate the basis for this asymmetric distribution of aaRSs, a global search for proteins interacting with the 20 aaRSs was conducted. The interaction between ValRS and the FoF1 ATP synthase complex here reported is of utmost interest and suggests a functional link between elements of the gene translation and energy production machineries.

National Security and Secret Evidence in Legislation and before the Courts: Exploring the Challenges. CEPS Liberty and Security in Europe No. 78/January 2015

This study provides a comparative analysis of the national legal regimes and practices governing the use of intelligence information as evidence in the United Kingdom, France, Germany, Spain, Italy, the Netherlands and Sweden. It explores notably how national security can be invoked to determine the classification of information and evidence as 'state secrets' in court proceedings and whether such laws and practices are fundamental rights- and rule of law-compliant. The study finds that, in the majority of Member States under investigation, the judiciary is significantly hindered in effectively adjudicating justice and guaranteeing the rights of the defence in ‘national security’ cases. The research also illustrates that the very term ‘national security’ is nebulously defined across the Member States analysed, with no national definition meeting legal certainty and “in accordance with the law” standards and a clear risk that the executive and secret services may act arbitrarily. The study argues that national and transnational intelligence community practices and cooperation need to be subject to more independent and effective judicial accountability and be brought into line with EU 'rule of law' standards.

The efficacy of Illinois' Sexual Assault Nurse Examiner (SANE) Pilot Program : a report to the Illinois General Assembly by the Illinois Criminal Justice Information Authority pursuant to Public Act 91-0529.

A sexual assault nurse examiner (SANE) is a registered nurse (R.N.) who has advanced education in conducting medical and forensic examinations of patients who are sexually victimized. SANE programs consist of SANEs as well as other professionals from community agencies that respond to sex crimes such as police departments, state's attorney's officers, and victim service agencies. Together these professionals work to achieve two primary objectives: 1) improve treatment of sexually assaulted victims who are admitted to hospital emergency departments; and 2) improve the quality of evidence collection and presentation to increase successful prosecution outcomes.

Evidence that the Bed Nucleus of the Stria Terminalis Contributes to the Modulation of Hypophysiotropic Corticotropin-Releasing Factor Cell Responses to Systemic Interleukin-1β

Systemic infection activates the hypothalamic-pituitary-adrenal (HPA) axis, and brainstem catecholamine cells have been shown to contribute to this response. However, recent work also suggests an important role for the central amygdala (CeA). Because direct connections between the CeA and the hypothalamic apex of the HPA axis are minimal, the present study investigated whether the bed nucleus of the stria terminalis (BNST) might act as a relay between them. This was done by using an animal model of acute systemic infection involving intravascular delivery of the proinflammatory cytokine interleukin-1 (IL-1, 1 g/kg). Unilateral ibotenic acid lesions encompassing the ventral BNST significantly reduced both IL-1-induced increases in Fos immunoreactivity in corticotropin-releasing factor (CRF) cells of the hypothalamic paraventricular nucleus (PVN) and corresponding increases in adrenocorticotropic hormone (ACTH) secretion. Similar lesions had no effect on CRF cell responses to physical restraint, suggesting that the effects of BNST lesions were not due to a nonspecific effect on stress responses. In further studies, we examined the functional connections between PVN, BNST, and CeA by combining retrograde tracing with mapping of IL-1-induced increases in Fos in BNST and CeA cells. In the case of the BNST, these studies showed that systemic IL-1 administration recruits ventral BNST cells that project directly to the PVN. In the case of the CeA, the results obtained were consistent with an arrangement whereby lateral CeA cells recruited by systemic IL-1 could regulate the activity of medial CeA cells projecting directly to the BNST. In conclusion, the present findings are consistent with the hypothesis that the BNST acts as a relay between the CeA and PVN, thereby contributing to CeA modulation of hypophysiotropic CRF cell responses to systemic administration of IL-1.

School vision screening, ages 5-16 years:The evidence-base for content, provision and efficacy

The optometric profession in the UK has a major role in the detection, assessment and management of ocular anomalies in children between 5 and 16 years of age. The role complements a variety of associated screening services provided across several health care sectors. The review examines the evidence-base for the content, provision and efficacy of these screening services in terms of the prevalence of anomalies such as refractive error, amblyopia, binocular vision and colour vision and considers the consequences of their curtailment. Vision screening must focus on pre-school children if the aim of the screening is to detect and treat conditions that may lead to amblyopia, whereas if the aim is to detect and correct significant refractive errors (not likely to lead to amblyopia) then it would be expedient for the optometric profession to act as the major provider of refractive (and colour vision) screening at 5-6 years of age. Myopia is the refractive error most likely to develop during primary school presenting typically between 8 and 12 years of age, thus screening at entry to secondary school is warranted. Given the inevitable restriction on resources for health care, establishing screening at 5 and 11 years of age, with exclusion of any subsequent screening, is the preferred option. © 2004 The College of Optometrists.

Cholecystokinin (CCK) and CCK receptor expression by human gliomas:evidence for an autocrine/paracrine stimulatory loop

Cholecystokinin (CCK) is a gut-brain peptide has been described to be able to induce mitosis according to recent studies. Additionally, conflicting data has been published on whether tumours of the central and peripheral nervous system in general, and gliomas in particular, express CCK receptors. In the present in vitro study we employed reverse transcription followed by the polymerase chain reaction (RT-PCR) to investigate whether mRNA for CCK-A and CCK-B receptors as well as CCK peptide itself is present in primary human gliomas and the U-87 MG GBM cell line. The data show that 14/14 (100%) of the primary gliomas exhibited mRNA expression for the CCK peptide gene and the B receptor including the U-87 MG cells, whereas, only 2/14 (14%) showed presence of the CCK-A receptor. The presence of CCK receptors together with CCK peptide expression itself suggests presence of an autocrine loop controlling glioma cell growth. In support of this conclusion, a neutralizing antibody against the CCK peptide exhibited a dose dependent inhibition of cell growth whereas, antagonists to CCK caused a dose depend inhibition of exogenous stimulated glioma cell growth in vitro, via the CCK-B receptor which is PKC activated. Assessment of apoptosis and proteasome activity were undertaken and we report that treatment with CCK antagonists decreased proteasome and increased caspase-3 activity. These data indicate that CCK peptide and CCK-B are abundant in human gliomas and they act to stimulate cell growth in an autocrine manner, primarily via the high affinity CCK-B receptor, which was blocked by antagonists to CCK, perhaps via apoptosis.

Sub-national responses to climate change in England:evidence from local area agreements

The machinery of governance to address climate change at the sub-national level in England continues to evolve. Drawing on documentary evidence and the views of civil servants and local authority officials from the English West Midlands, this article explores the process through an examination of the inclusion of climate change indicators in the recent round of Local Area Agreements (LAAs), negotiated between central government and local authorities and Local Strategic Partnerships. Considerable popularity has been accorded these indicators nationally, but there are important variations in the pattern of take up. Moreover, significant uncertainties surround the contribution of local measures to reduce CO2 emissions and the targets attached to measures to adapt to climate change are seen as undemanding. Conversely, the impending Carbon Reduction Commitment will act as a powerful incentive for public bodies to cut CO2 emissions from their estates. Although potentially contributing to greater coherence in tackling climate change, achieving collective action through LAAs will prove problematic.

An introduction to forensic linguistics:language in evidence

From the accusation of plagiarism in The Da Vinci Code, to the infamous hoaxer in the Yorkshire Ripper case, the use of linguistic evidence in court and the number of linguists called to act as expert witnesses in court trials has increased rapidly in the past fifteen years. An Introduction to Forensic Linguistics: Language in Evidence provides a timely and accessible introduction to this rapidly expanding subject. Using knowledge and experience gained in legal settings – Malcolm Coulthard in his work as an expert witness and Alison Johnson in her work as a West Midlands police officer – the two authors combine an array of perspectives into a distinctly unified textbook, focusing throughout on evidence from real and often high profile cases including serial killer Harold Shipman, the Bridgewater Four and the Birmingham Six. Divided into two sections, 'The Language of the Legal Process' and 'Language as Evidence', the book covers the key topics of the field. The first section looks at legal language, the structures of legal genres and the collection and testing of evidence from the initial police interview through to examination and cross-examination in the courtroom. The second section focuses on the role of the forensic linguist, the forensic phonetician and the document examiner, as well as examining in detail the linguistic investigation of authorship and plagiarism. With research tasks, suggested reading and website references provided at the end of each chapter, An Introduction to Forensic Linguistics: Language in Evidence is the essential textbook for courses in forensic linguistics and language of the law.

The Defamation Act 2013 and CPR 3.4 and 24:a sting in causation’s tail

Examines the Court of Appeal judgment in Tesla Motors Ltd v BBC on whether the claim that a review of a vehicle on the BBC "Top Gear" programme constituted malicious falsehood should be struck out under CPR 3.4(2) on the ground there was insufficient evidence to show that any loss in revenue suffered by the manufacturer was attributable to the review. Considers the implications of the decision for commercial claimants seeking to establish that defamation caused them "serious harm", which, pursuant to the Defamation Act 2013 s.1(2), requires evidence of actual or likely serious financial loss.

Innocent but proven guilty:eliciting internalized false confessions using doctored-video evidence

More powerful computers and affordable digital-video equipment means that desktop-video editing is now accessible and popular. In two experiments, we investigated whether seeing fake-video evidence, or simply being told that video evidence exists, could lead people to believe they committed an act they never did. Subjects completed a computerized gambling task, and when they returned later the same day, we falsely accused them of cheating on the task. All of the subjects were told that incriminating video evidence existed, and half were also exposed to a fake video. See-video subjects were more likely to confess without resistance, and to internalize the act than told-video subjects, and see-video subjects tended to confabulate details more often than told-video subjects. We offer a metacognitive-based account of our results. Copyright © 2008 John Wiley & Sons, Ltd.

Factors predicting recommendations for civil commitment of sexually violent predators under Florida's Jimmy Ryce Act

This study investigated the factors considered by forensic examiners when evaluating sexually violent predators (SVP) for civil commitment under Florida's “Jimmy Ryce Act.” The project was funded by a pre-doctoral research grant awarded by the Association for the Treatment of Sexual Abusers (ATSA). ^ This study proposed two specific research questions. First, what is the direct relationship between actuarial risk assessment scores and recommendations for sex offender civil commitment? Second, which other variables are likely to influence SVP commitment decisions, and to what degree? The purpose of the study was to determine if risk assessment practices are evidence-based, and whether offenders selected for commitment meet statutory criteria. ^ The purposive sample of 450 SVPs was drawn from the population of sex offenders evaluated for civil commitment in Florida between July 1, 2000 and June 30, 2001. Data were extracted from SVP evaluations provided by the Florida Department of Children and Families. Using multivariate logistic regression, this correlational research design examined the relationship between the dependent variable, commitment decision, and several sets of independent variables. The independent variables were derived from a review of the literature, and were grouped conceptually according to their degree of correlation with sex offense recidivism. Independent variables included diagnoses, actuarial risk assessment scores, empirically validated static and dynamic risk factors, consensus based risk factors, evaluator characteristics, and demographics. This study investigated the degree to which the identified variables predicted civil commitment decisions. ^ Logistic regression results revealed that the statistically significant predictors of recommendations for sex offender civil commitment were actuarial risk assessment scores, diagnoses of Pedophilia and Paraphilia NOS, psychopathy, younger age of victim, and non-minority race. Discriminant function analysis confirmed that these variables correctly predicted commitment decisions in 90% of cases. ^ It appears that civil commitment evaluators in Florida used empirically-based assessment procedures, and did not make decisions that were heavily influenced by extraneous factors. SVPs recommended for commitment consistently met the criteria set forth by the U.S. Supreme Court in Hendricks v. Kansas (1997): they suffered from a mental abnormality predisposing them to sexual violence, and risk assessment determined that they were likely to reoffend. ^

True and false confessions to an intentional act: A novel experimental paradigm

Due to the powerful nature of confession evidence, it is imperative that we investigate the factors that affect the likelihood of obtaining true and false confessions. Previous research has been conducted with a paradigm limited to the study of false confessions to an act of negligence, thereby limiting the generalizability of the findings. The first goal of the current study was to introduce a novel paradigm involving a more serious, intentional act that can be used in the study of both true and false confessions. The second goal was to explore the effects of two police interrogation tactics, minimization and an offer of leniency, on true and false confession rates. ^ Three hundred and thirty-four undergraduates at a large southeastern university were recruited to participate in a study on problem-solving and decision-making. During the course of the laboratory experiment, participants were induced to intentionally break or not break an experimental rule, an act that was characterized as “cheating.” All participants (i.e., both innocent and guilty) were later accused of the act and interrogated. For half of the participants, the interrogator used minimization tactics, which involved downplaying the seriousness of the offense, expressing sympathy, and providing face-saving excuses, in order to encourage the participant to confess. An offer of leniency was also manipulated in which half the participants were offered a “deal” that involved the option of confessing and accepting a known punishment or not confessing and facing the threat of harsher punishment. Results indicated that guilty persons were more likely to confess than innocent persons, and that the use of minimization and an explicit offer of leniency increased both the true and false confession rates. Furthermore, a cumulative effect of techniques was observed, such that the diagnosticity of the interrogation (the ratio of true confessions to false confessions) decreased as the number of techniques used increased. Taken together, the results suggest that caution should be used when implementing these techniques in the interrogation room. ^