bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forensic psychiatric assessment in European Union member states
Authors: Dressing H. , Salize H. J. 
Published: March 2006

Objective:  To provide a structured description and cross‐boundary comparison of legal frameworks and training standards relevant for forensic psychiatric assessment in European Union member states before the extension in May 2004.Method:  Information on legislation and practice concerning the assessment of mentally disordered offenders was gathered by means of a detailed, structured questionnaire which was filled in by national experts.Results:  Legal frameworks for the assessment and reassessment of mentally disordered offenders and professional training standards in forensic psychiatry vary markedly across EU member states.Conclusion:  Currently a cross‐boundary harmonization of legal concepts appears hard to achieve. At least a formal construction and implementation of specialist training standards in forensic psychiatry would appear desirable.
Randomized controlled trial of a cannabis‐focused intervention for young people with first‐episode psychosis
Authors: Edwards J. , Elkins K. , Hinton M. , Harrigan S. M. , Donovan K. , Athanasopoulos O. , McGorry P. D. 
Published: March 2006

Objective:  To evaluate a cannabis‐focused intervention (cannabis and psychosis therapy: CAP) for patients continuing to use cannabis following initial treatment for first‐episode psychosis (FEP).Method:  Consecutive admissions to an early psychosis program were screened and consenting individuals using cannabis in the 4 weeks prior to assessment participated. A single‐blind randomized controlled trial compared CAP (n = 23) with a clinical control condition (psychoeducation, PE; n = 24).Results:  There were no significant differences between the CAP and PE groups on cannabis use at end of treatment and 6 months post‐intervention. There were no significant group differences on psychopathology and functional ratings at follow‐up. A significant reduction in cannabis use was observed for both groups over time.Conclusion:  PE and specific cannabis‐focused intervention are associated with similar reductions in cannabis use in an FEP cohort. Simple interventions may therefore be worth considering prior to intensive psychotherapeutic efforts with this population.
Polymorphic light eruption may be associated with cigarette smoking and alcohol consumption
Authors: Mentens Greet , Lambert Julien , Nijsten Tamar 
Published: March 2006

Background: Although the genetic influence on polymorphic light eruption (PLE) is well established, the role of lifestyle factors is less well defined.Methods: A retrospective case–control study was conducted that included 74 PLE patients and 102 controls. Each participant was interviewed about demographic, disease and lifestyle characteristics such as smoking, alcohol consumption and use of medications. Multivariate logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI).Results: Compared with the controls, patients with PLE were significantly more likely to be younger females (P<0.05). Univariate analysis did not show a significant association between any of the smoking‐related questions and PLE. However, after adjusting for gender and drinking alcohol, patients with PLE were significantly more likely to smoke 15 cigarettes or more daily [adjusted OR=4.06 (95% CI=1.19, 13.80) compared with 0 daily cigarettes] than controls. Participants who consumed six or more drinks a week were less likely to have PLE [adjusted OR=0.24 (95% CI=0.07, 0.80)]. In contrast, women who used oral anticonceptives for a longer period were four‐fold more likely to have PLE [adjusted OR=4.74 (95% CI=1.33, 16.86)].Conclusion: Several lifestyle factors may be associated with PLE, but further studies are warranted to confirm these retrospective findings.
Reduction of the UV burden to indoor tanners through new exposure schedules: a pilot study
Authors: Miller Sharon A. , Coelho Sergio G. , Zmudzka Barbara Z. , Beer Janusz Z. 
Published: March 2006

Background: The development of new pigmentation (tan) in human skin after UV exposure requires several days. Once it is developed, the tan can last for weeks. Current recommendations for tanning exposure schedules in the USA (FDA Letter to Manufacturers: Policy on maximum timer interval and exposure schedule for sunlamps, August 21, 1986) allow exposures three times per week for the development of a tan, and one to two times per week for maintenance exposures. However, this policy is often interpreted in the indoor tanning industry as allowing three exposures per week on a continuous basis. We believe that the reduction of the recommended cumulative dose to indoor tanners should be explored. Two approaches for achieving this are (1) decreasing the number of exposures and (2) increasing the time interval between exposures. To explore such changes, we conducted a pilot study.Methods: The pilot study involved three exposure schedules (evaluated on each of six subjects) that evolved throughout the course of the study. Digital photography, visual assessment and diffuse reflectance spectrometry were used to assess skin color changes. The six pilot subjects were studied for 8–18 weeks. The changes in skin color obtained through the use of the different exposure schedules were compared with changes reported by Caswell (Caswell M, The kinetics of the tanning response to tanning bed exposures, Photodermatol Photoimmunol Photomed 2000: 16: 10–14) who used schedules based on current recommendations.Results: Two out of the three experimental schedules produced tans comparable with those reported by Caswell. In these two schedules, cumulative doses were a factor of 2–3 below doses from current schedules.Conclusion: The UV burden to indoor tanners can be substantially reduced without compromising the cosmetic effect. These results need to be confirmed in a larger study.
A critical analysis of UK public health policies in relation to diet and nutrition in low‐income households
Authors: Attree Pamela 
Published: March 2006

AbstractDiet and nutrition, particularly among low‐income groups, is a key public health concern in the UK. Low levels of fruit and vegetable consumption, and obesity, especially among children, have potentially severe consequences for the future health of the nation. From a public health perspective, the UK government's role is to help poorer families make informed choices within healthy frameworks for living. However, the question is – to what extent are such policies in accordance with lay experiences of managing diet and nutrition on a low‐income? This paper critically examines contemporary public health policies aimed at improving diet and nutrition, identifying the underlying theories about the influences on healthy eating in poor families, and exploring the extent to which these assumptions are based on experiential accounts. It draws on two qualitative systematic reviews – one prioritizing low‐income mothers’ accounts of ‘managing’ in poverty; and the other focusing on children's perspectives. The paper finds some common ground between policies and lay experiences, but also key divergencies. Arguably, the emphasis of public health policy on individual behaviour, coupled with an ethos of empowered consumerism, underplays material limitations on ‘healthy eating’ for low‐income mothers and children. Health policies fail to take into account the full impact of structural influences on food choices, or recognize the social and emotional factors that influence diet and nutrition. In conclusion, it is argued that while health promotion campaigns to improve low‐income families’ diets do have advantages, these are insufficient to outweigh the negative effects of poverty on nutrition.
Cell-Type-Specific Repression of Internal Ribosome Entry Site Activity by Double-Stranded RNA-Binding Protein 76
Authors: Merrill Melinda K. , Dobrikova Elena Y. , Gromeier Matthias 
Published: March 2006

ABSTRACT

Translation of picornavirus plus-strand RNA genomes occurs via internal ribosomal entry at highly structured 5′ untranslated regions. In addition to canonical translation factors, translation rate is likely influenced by supplementary host and viral
trans
-acting factors. We previously reported that insertion of a heterologous human rhinovirus type 2 internal ribosomal entry site (IRES) into the poliovirus (PV) genome, generating the chimeric virus PV-RIPO, selectively abrogates viral translation and propagation in neurons, which eliminate poliovirus's signature neuropathogenicity. While severely deficient in cells of neuronal lineage, the rhinovirus IRES promotes efficient propagation of PV-RIPO in cancer cells. Tumor-specific IRES function can be therapeutically exploited to direct viral cytotoxicity to cancer cells. Neuron-glioma heterokaryon analysis implicates neuronal
trans-
dominant inhibition in this effect, suggesting that host
trans
-acting factors repress IRES function in a cell-type-specific manner. We identified a set of proteins from neuronal cells with affinity for the rhinovirus IRES, including double-stranded RNA-binding protein 76 (DRBP76). DRBP76 associates with the IRES in neuronal but not in malignant glioma cells. Moreover, DRBP76 depletion in neuronal cells enhances rhinovirus IRES-driven translation and virus propagation. Our observations suggest that cell-type-specific association of DRBP76 with the rhinovirus IRES represses PV-RIPO translation and propagation in neuronal cells.
African Swine Fever Virus pB119L Protein Is a Flavin Adenine Dinucleotide-Linked Sulfhydryl Oxidase
Authors: Rodríguez Irene , Redrejo-Rodríguez Modesto , Rodríguez Javier M. , Alejo Alí , Salas José , Salas María L. 
Published: March 2006

ABSTRACT
Protein pB119L of African swine fever virus belongs to the Erv1p/Alrp family of sulfhydryl oxidases and has been described as a late nonstructural protein required for correct virus assembly. To further our knowledge of the function of protein pB119L during the virus life cycle, we have investigated whether this protein possesses sulfhydryl oxidase activity, using a purified recombinant protein. We show that the purified protein contains bound flavin adenine dinucleotide and is capable of catalyzing the formation of disulfide bonds both in a protein substrate and in the small molecule dithiothreitol, the catalytic activity being comparable to that of the Erv1p protein. Furthermore, protein pB119L contains the cysteines of its active-site motif CXXC, predominantly in an oxidized state, and forms noncovalently bound dimers in infected cells. We also show in coimmunoprecipitation experiments that protein pB119L interacts with the viral protein pA151R, which contains a CXXC motif similar to that present in thioredoxins. Protein pA151R, in turn, was found to interact with the viral structural protein pE248R, which contains disulfide bridges and belongs to a class of myristoylated proteins related to vaccinia virus L1R, one of the substrates of the redox pathway encoded by this virus. These results suggest the existence in African swine fever virus of a system for the formation of disulfide bonds constituted at least by proteins pB119L and pA151R and identify protein pE248R as a possible final substrate of this pathway.
Herpes Simplex Virus gE/gI Must Accumulate in the
trans
-Golgi Network at Early Times and Then Redistribute to Cell Junctions To Promote Cell-Cell Spread
Authors: Farnsworth Aaron , Johnson David C. 
Published: March 2006

ABSTRACT

Herpes simplex virus (HSV) glycoprotein heterodimer gE/gI is necessary for virus spread in epithelial and neuronal tissues. Deletion of the relatively large gE cytoplasmic (CT) domain abrogates the ability of gE/gI to mediate HSV spread. The gE CT domain is required for the sorting of gE/gI to the
trans
-Golgi network (TGN) in early stages of virus infection, and there are several recognizable TGN sorting motifs grouped near the center of this domain. Late in HSV infection, gE/gI, other viral glycoproteins, and enveloped virions redistribute from the TGN to epithelial cell junctions, and the gE CT domain is also required for this process. Without the gE CT domain, newly enveloped virions are directed to apical surfaces instead of to cell junctions. We hypothesized that the gE CT domain promotes virus envelopment into TGN subdomains from which nascent enveloped virions are sorted to cell junctions, a process that enhances cell-to-cell spread. To characterize elements of the gE CT domain involved in intracellular trafficking and cell-to-cell spread, we constructed a panel of truncation mutants. Specifically, these mutants were used to address whether sorting to the TGN and redistribution to cell junctions are necessary, and sufficient, for gE/gI to promote cell-to-cell spread. gE-519, lacking 32 C-terminal residues, localized normally to the TGN early in infection and then trafficked to cell junctions at late times and mediated virus spread. By contrast, mutants gE-495 (lacking 56 C-terminal residues) and gE-470 (lacking 81 residues) accumulated in the TGN but did not traffic to cell junctions and did not mediate cell-to-cell spread. A fourth mutant, gE-448 (lacking most of the CT domain), did not localize to cell junctions and did not mediate virus spread. Therefore, the capacity of gE/gI to promote cell-cell spread requires early localization to the TGN, but this is not sufficient for virus spread. Additionally, gE CT sequences between residues 495 and 519, which contain no obvious cell sorting motifs, are required to promote gE/gI traffic to cell junctions and cell-to-cell spread.
Membrane-Anchored Inhibitory Peptides Capture Human Immunodeficiency Virus Type 1 gp41 Conformations That Engage the Target Membrane prior to Fusion
Authors: Melikyan Gregory B. , Egelhofer Marc , von Laer Dorothee 
Published: March 2006

ABSTRACT
Soluble peptides derived from the C-terminal heptad repeat domain of human immunodeficiency virus type 1 (HIV-1) gp41 are potent inhibitors of HIV-1 entry and gp41-induced fusion. Target membrane-anchored variants of these peptides have been shown to retain inhibitory activity. Both soluble and membrane-anchored C peptides (MACs) are thought to block fusion by binding to the N-terminal coiled coil domain of gp41 and preventing formation of the final six-helix bundle structure. However, interactions of target MACs with gp41 must be restricted to a subset of trimers that have their hydrophobic fusion peptides inserted into the target membrane. This unique feature of MACs was used to identify the intermediate step of fusion at which gp41 engaged the target membrane. Fusion between HIV envelope-expressing effector cells and target cells was measured by fluorescence microscopy. Expression of MACs in target cells led to less than twofold reduction in the extent of fusion. However, when reaction was first arrested by adding lysolipids that disfavored membrane merger, and the lipids were subsequently removed by washing, control cells supported fusion, whereas those that expressed MACs did not. The drastically improved potency of MACs implies that, at lipid-arrested stage, gp41 bridges the viral and target cell membranes and therefore more optimally binds the membrane-anchored peptides. Experimental demonstration of this intermediate shows that, similar to fusion induced by many other viral glycoproteins, engaging the target membrane by HIV-1 gp41 permits coupling between six-helix bundle formation and membrane merger.
Modulation of Poliovirus Replicative Fitness in HeLa Cells by Deoptimization of Synonymous Codon Usage in the Capsid Region
Authors: Burns Cara Carthel , Shaw Jing , Campagnoli Ray , Jorba Jaume , Vincent Annelet , Quay Jacqueline , Kew Olen 
Published: March 2006

ABSTRACT

We replaced degenerate codons for nine amino acids within the capsid region of the Sabin type 2 oral poliovirus vaccine strain with corresponding nonpreferred synonymous codons. Codon replacements were introduced into four contiguous intervals spanning 97% of the capsid region. In the capsid region of the most highly modified virus construct, the effective number of codons used (

N
C

) fell from 56.2 to 29.8, the number of CG dinucleotides rose from 97 to 302, and the G+C content increased from 48.4% to 56.4%. Replicative fitness in HeLa cells, measured by plaque areas and virus yields in single-step growth experiments, decreased in proportion to the number of replacement codons. Plaque areas decreased over an ∼10-fold range, and virus yields decreased over an ∼65-fold range. Perhaps unexpectedly, the synthesis and processing of viral proteins appeared to be largely unaltered by the restriction in codon usage. In contrast, total yields of viral RNA in infected cells were reduced ∼3-fold and specific infectivities of purified virions (measured by particle/PFU ratios) decreased ∼18-fold in the most highly modified virus. The replicative fitness of both codon replacement viruses and unmodified viruses increased with the passage number in HeLa cells. After 25 serial passages (∼50 replication cycles), most codon replacements were retained, and the relative fitness of the modified viruses remained well below that of the unmodified virus. The increased replicative fitness of high-passage modified virus was associated with the elimination of several CG dinucleotides. Potential applications for the systematic modulation of poliovirus replicative fitness by deoptimization of codon usage are discussed.
Primary Simian Immunodeficiency Virus SIVmnd-2 Infection in Mandrills (
Mandrillus sphinx
)
Authors: Onanga Richard , Souquière Sandrine , Makuwa Maria , Mouinga-Ondeme Augustin , Simon François , Apetrei Cristian , Roques Pierre 
Published: March 2006

ABSTRACT

Mandrills are the only nonhuman primate (NHP) naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd-1 and SIVmnd-2. We have already reported that the high SIVmnd-1 replication during primary infection contrasts with only transient changes in CD4
+
and CD8
+
cell counts. Since early virus-host interactions predict viral control and disease progression in human immunodeficiency virus-infected patients, we investigated the dynamics of SIVmnd-2 primary infection in mandrills to examine the impact on immune effectors in blood and lymph nodes (LNs). To avoid in vitro strain selection, all mandrills in this study received plasma from SIVmnd-2-infected mandrills. SIVmnd-2 plasma viremia peaked at 10
7
to 10
8
RNA copies/ml between days 7 and 10. This peak was followed in all four monkeys by a decline in virus replication, with a set point level of 10
5
to 10
6
RNA copies/ml at day 42 postinfection (p.i.). Viral DNA load in PBMC and LNs also peaked between days 7 and 10 (10
5
to 10
6
DNA copies/10
6
cells) and stabilized at 10
3
to 10
4
DNA copies/10
6
cells during the chronic phase. Anti-SIVmnd-2 antibodies were detected starting from days 28 to 32. A transitory decline of CD3
+
CD4
+
cells in the LNs occurred in animals with high peak VLs. CD4
+
and CD8
+
T-cell activation in blood and LNs was noted between days 5 and 17 p.i., surrounding the peak of viral replication. This was most significant in the LNs. Activation markers then returned to preinfection values despite continuous and active viral replication during the chronic infection. The dynamics of SIVmnd-2 infection in mandrills showed a pattern similar to that of SIVmnd-1 infection. This might be a general feature of nonpathogenic SIV natural African NHP models.
The Peptide-Binding and ATPase Domains of Recombinant hsc70 Are Required To Interact with Rotavirus and Reduce Its Infectivity
Authors: Pérez-Vargas Jimena , Romero Pedro , López Susana , Arias Carlos F. 
Published: March 2006

ABSTRACT
The heat shock cognate protein hsc70 has been implicated as a postattachment cell receptor for rotaviruses. Here we show that hsc70 interacts specifically with rotaviruses through its peptide-binding domain, since a recombinant full-length hsc70 protein and its peptide-binding domain, but not its ATPase domain, bound triple-layered particles in a solid-phase assay, and known ligands of hsc70 competed this binding. The peptide ligands of hsc70 were also shown to block rotavirus infectivity when added to cells before virus infection, suggesting that hsc70 on the surface of MA104 cells also interacts with the virus through its peptide-binding domain and that this interaction is important for virus entry. When purified infectious virus was incubated with soluble hsc70 in the presence of the cochaperone hsp40 and ATP and then pelleted through a sucrose cushion, the recovered virus had lost 60% of its infectivity, even though hsc70 was not detected in the pellet fraction. The hsc70-treated virus showed slightly different reactivities with monoclonal antibodies and was more susceptible to heat and basic pHs than the untreated virus, suggesting that hsc70 induces a subtle conformational change in the virus that results in a reduction of its infectivity. The relevance of the ATPase activity of hsc70 for reducing virus infectivity was demonstrated by the finding that in the presence of a nonhydrolyzable analogue of ATP, virus infectivity was not affected, and a mutant protein lacking ATPase activity failed to reduce virus infection. Altogether, these results suggest that during cell infection, the interaction of the virus with hsc70 on the surface of MA104 cells results in a conformational change of virus particles that facilitates their entry into the cell cytoplasm.
Nonstructural Protein of Infectious Bursal Disease Virus Inhibits Apoptosis at the Early Stage of Virus Infection
Authors: Liu Meihong , Vakharia Vikram N. 
Published: March 2006

ABSTRACTInfectious bursal disease virus (IBDV), the causative agent of a highly contagious disease in chickens, carries a small nonstructural protein (NS). This protein has been implicated to play a role in the induction of apoptosis. In this study, we investigate the kinetics of viral replication during a single round of viral replication and examine the mechanism of IBDV-induced apoptosis. Our results show that it is caspase dependent and activates caspases 3 and 9. Nuclear factor kappa B (NF-κB) is also activated and is required for IBDV-induced apoptosis. The NF-κB inhibitor MG132 completely inhibited IBDV-induced DNA fragmentation, caspase 3 activation, and NF-κB activation. To study the function of the NS protein in this context, we generated the recombinant rGLS virus and an NS knockout mutant, rGLSNSΔ virus, using reverse genetics. Comparisons of the replication kinetics and markers for virally induced apoptosis indicated that the NS knockout mutant virus induces earlier and increased DNA fragmentation, caspase activity, and NF-κB activation. These results suggest that the NS protein has an antiapoptotic function at the early stage of virus infection.
Human Chromosome 2 Carries a Gene Required for Production of Infectious Human Immunodeficiency Virus Type 1
Authors: Coskun Ayse K. , van Maanen Marc , Nguyen Van , Sutton Richard E. 
Published: March 2006

ABSTRACT
Human immunodeficiency virus type 1 (HIV) replicates only in certain primate cells. In murine cells expressing cyclin T1, a posttranscriptional block exists such that small amounts of capsid and little infectious virus are released. This block is relieved in part by fusion with human cells. Here we have tested a panel of mouse-human somatic cell hybrids for production of infectious virus. Only those containing human chromosome 2 were permissive, which correlated with capsid production. The effect was specific to HIV in that release of murine leukemia virus was minimally affected by the presence of chromosome 2. Although expression of Vpu markedly increased capsid production in the absence of chromosome 2, it did not result in a corresponding increase in infectious HIV. The presence of chromosome 2 did not have consistent effects on the amount of unspliced viral RNA, whereas the amount of cell-associated Gag p55 was increased a fewfold. These results suggest that processing of HIV Gag can be corrected by one or more genes present on human chromosome 2 to allow production of infectious HIV from murine cells.