Conformational selection guides β-arrestin recruitment at a biased G protein-coupled receptor.

G protein-coupled receptors (GPCRs) recruit β-arrestins to coordinate diverse cellular processes, but the structural dynamics driving this process are poorly understood. Atypical chemokine receptors (ACKRs) are intrinsically biased GPCRs that engage β-arrestins but not G proteins, making them a model system for investigating the structural basis of β-arrestin recruitment. Here, we performed nuclear magnetic resonance (NMR) experiments on CH-ε-methionine-labeled ACKR3, revealing that β-arrestin recruitment is associated with conformational exchange at key regions of the extracellular ligand-binding pocket and intracellular β-arrestin-coupling region.

Splice switching an oncogenic ratio of SmgGDS isoforms as a strategy to diminish malignancy.

The chaperone protein SmgGDS promotes cell-cycle progression and tumorigenesis in human breast and nonsmall cell lung cancer. Splice variants of SmgGDS, named SmgGDS-607 and SmgGDS-558, facilitate the activation of oncogenic members of the Ras and Rho families of small GTPases through membrane trafficking via regulation of the prenylation pathway. SmgGDS-607 interacts with newly synthesized preprenylated small GTPases, while SmgGDS-558 interacts with prenylated small GTPases.

Evidence that a threshold of serine/arginine-rich (SR) proteins recruits CFIm to promote rous sarcoma virus mRNA 3' end formation.

The weak polyadenylation site (PAS) of Rous sarcoma virus (RSV) is activated by the juxtaposition of SR protein binding sites within the spatially separate negative regulator of splicing (NRS) element and the env RNA splicing enhancer (Env enhancer), which are far upstream of the PAS. Juxtaposition occurs by formation of the NRS - 3' ss splicing regulatory complex and is thought to provide a threshold of SR proteins that facilitate long-range stimulation of the PAS. We provide evidence for the threshold model by showing that greater than three synthetic SR protein binding sites are needed to substitute for the Env enhancer, that either the NRS or Env enhancer alone promotes polyadenylation when the distance to the PAS is decreased, and that SR protein binding sites promote binding of the polyadenylation factor cleavage factor I (CFIm) to the weak PAS.

The Overall Survival, Complication-Free Survival, and Related Complications of Combined Tooth-Implant Fixed Partial Dentures: A Literature Review.

This paper reviews the literature regarding possible complications, complication-free survival, and overall survival of fixed dental prostheses that use both implants and natural teeth as abutments. The paper also provides clinical guidelines for treatment based on this literature review. An electronic search utilizing the MEDLINE, BIOSIS Citation Index, and Web of Science™ Core Collection databases was undertaken, and a review of the 25 selected texts studying 22 different patient cohorts was carried out.

Attitudes towards Prosthodontic Clinical Decision-Making for Edentulous Patients among South West Deanery Dental Foundation Year One Dentists.

The aim of this study was to describe Dental Foundation year one dentists' attitudes towards prosthodontic decision making for edentulous patients, and identify whether there are gender differences in these attitudes. All South West Deanery trainees were invited to take part in the study between May and June 2011 and a previously piloted questionnaire was administered to the trainees by their training programme directors. The questionnaire posed questions based upon a clinical scenario of discussing treatment options with patients.

An antifungal coating for dental silicones composed of chlorhexidine nanoparticles.

Objectives: The aims of this study were to synthesise a range of chlorhexidine-containing nanoparticles (CHX-NPs), and investigate the feasibility of using these as an antifungal coating for dental silicones.

Methods: CHX-NPs were precipitated in aqueous reaction by mixing solutions of CHX digluconate with solutions of sodium triphosphate (TP), trimetaphosphate (TMP) or hexametaphosphate (HMP). CHX-NPs were deposited on commercial dental silicones by immersion coating, and these were characterised for hydrophilicity (contact angle) and water uptake (mass change).

A pilot randomized controlled trial to increase smoking cessation by maintaining National Health Service Stop Smoking Service attendance.

Objectives: The National Health Service (NHS) Stop Smoking Service (SSS) is an extremely cost-effective method of enabling smoking cessation. However, the SSS is only used by a minority of smokers. Developing interventions to maintain service attendance may help to increase the number of quitters.

Induction of strong HIV-1-specific CD4+ T-cell responses using an HIV-1 gp120/NefTat vaccine adjuvanted with AS02A in antiretroviral-treated HIV-1-infected individuals.

Background: Induction of HIV-1-specific CD4(+) T-cell responses by therapeutic vaccination represents an attractive intervention to potentially increase immune control of HIV-1.

Methods: We performed a double-blinded, randomized, placebo-controlled clinical trial to determine the safety and immunogenicity of GlaxoSmithKline Biologicals' HIV-1 gp120/NefTat subunit protein vaccine formulated with the AS02(A) Adjuvant System in subjects with well-controlled chronic HIV-1 infection on highly active antiretroviral therapy. Ten individuals received the vaccine; whereas adjuvant alone or placebo was given to 5 subjects each.

The prevalence of mental health problems among users of NHS stop smoking services: effects of implementing a routine screening procedure.

Background: Tobacco dependence among people with mental health problems is an issue that deserves attention both from a clinical and from a public health perspective. Research suggests that Stop Smoking Services often fail to ask clients about underlying mental health problems and thus fail to put in place the treatment adaptations and liaison procedures often required to meet the needs of clients with a mental health condition who want to stop smoking. This study assesses the recording of mental health problems in a large NHS stop smoking service in England and examines the effect of implementing a short screening procedure on recording mental health conditions.

Vaccine-induced HIV seropositivity: a problem on the rise.

Background: Vaccine-induced antibodies to envelope proteins frequently cause HIV seroconversion in uninfected recipients of HIV vaccine candidates and may thus have an impact on the vaccinee's ability to donate blood or acquire a life insurance policy.

Objective: To determine the occurrence of positive test results when commonly used HIV immunoassays are used to screen sera of HIV-uninfected volunteers who received an adjuvanted HIV-1 vaccine candidate containing HIV-1 antigens p24, reverse transcriptase, Nef and p17.

Study Design: Sera of 50 subjects who received this polyprotein vaccine in a single center in Belgium were tested with 6 HIV screening assays and 1 confirmation test.

Strong and persistent CD4+ T-cell response in healthy adults immunized with a candidate HIV-1 vaccine containing gp120, Nef and Tat antigens formulated in three Adjuvant Systems.

This randomized double-blind study aimed to determine the safety and immunogenicity of a gp120/NefTat candidate human immunodeficiency virus type 1 (HIV-1) vaccine formulated with one of three different Adjuvant Systems (AS02(A), AS02(V) and AS01(B)) in healthy HIV-seronegative adults. All vaccine formulations induced strong HIV-specific CD4(+) T-cell responses characterized by high lymphoproliferative capacity and IL-2 production that were still detectable 18 months after last immunization, with strongest responses seen in the AS01(B) group. Broad coverage was demonstrated against gp120, and to a lesser extent Nef, derived from the most common circulating clades (B, C and circulating recombinant form [CRF]-01).

The delivery of stop smoking support to people with mental health conditions: a survey of NHS stop smoking services.

Background: People with mental health problems exhibit smoking rates up to three times that of the general population. Metabolic interactions between hydrocarbon agents in tobacco smoke and some antipsychotic drugs account for a change in medication metabolism on stopping smoking, and potentially for increased blood levels. Nicotine withdrawal can mimic or exacerbate symptoms of mental illness.

A glycine-rich domain of hnRNP H/F promotes nucleocytoplasmic shuttling and nuclear import through an interaction with transportin 1.

Heterogeneous nuclear ribonucleoprotein (hnRNP) H and F are members of a closely related subfamily of hnRNP proteins that are implicated in many aspects of RNA processing. hnRNP H and F are alternative splicing factors for numerous U2- and U12-dependent introns. The proteins have three RNA binding domains and two glycine-rich domains and localize to both the nucleus and cytoplasm, but little is known about which domains govern subcellular localization or splicing activity.

Effect of age, polymicrobial disease, and maternal HIV status on treatment response and cause of severe pneumonia in South African children: a prospective descriptive study.

Background: HIV-related pneumonia is the main cause of paediatric hospital admissions in southern Africa. We aimed to measure predictors of treatment failure and the cause of non-responsive pneumonia in children admitted to hospital with severe pneumonia in Durban, South Africa.

Methods: We investigated 358 children aged 1-59 months who presented with WHO-defined severe or very severe pneumonia.

The introduction of a new assessment system in restorative dentistry: the undergraduate and patient experience.

In 2000, the University of Bristol Dental School Division of Restorative Dentistry carried out a review of the assessment methods used within the undergraduate programme. Following this review, a number of key recommendations were made and the system of formative assessment within the division was changed. Audits were conducted immediately prior to the introduction of the new system and 2 years after it had been introduced, the results of these audits are presented.

Age dependence of adenovirus-specific neutralizing antibody titers in individuals from sub-Saharan Africa.

We assessed neutralizing antibody titers to adenovirus serotype 5 (Ad5) and six rare adenovirus serotypes, serotypes 11, 35, 50, 26, 48, and 49, in pediatric populations in sub-Saharan Africa. We observed a clear age dependence of Ad5-specific neutralizing antibody titers. These data will help to guide the development of Ad vector-based vaccines for human immunodeficiency virus type 1 and other pathogens.

Lack of association between the nasopharyngeal carriage of Streptococcus pneumoniae and Staphylococcus aureus in HIV-1-infected South African children.

We investigated the nasopharyngeal carriage of Streptococcus pneumoniae and Staphylococcus aureus in 355 children hospitalized with severe pneumonia. Of the children, 239 (67.3%) were human immunodeficiency virus (HIV)-1 positive; 169 (47.

A survey of staff attitudes to smoking-related policy and intervention in psychiatric and general health care settings.

Background: Although the move to smoke-free hospital settings is generally a popular initiative, it may be a more challenging and controversial issue in mental health care. A survey was carried out to investigate differences in attitudes between clinical staff in psychiatric and general medical settings to smoke-free policy and intervention.

Method: The sample comprised 2574 NHS staff working in two Acute Hospital Trusts and one Mental Health Trust in England.

Heterogeneous nuclear ribonucleoprotein H is required for optimal U11 small nuclear ribonucleoprotein binding to a retroviral RNA-processing control element: implications for U12-dependent RNA splicing.

An RNA-processing element from Rous sarcoma virus, the negative regulator of splicing (NRS), represses splicing to generate unspliced RNA that serves as mRNA and as genomic RNA for progeny virions and also promotes polyadenylation of the unspliced RNA. Integral to NRS function is the binding of U1 small nuclear ribonucleoprotein (snRNP), but its binding is controlled by U11 snRNP that binds to an overlapping site. U11 snRNP, the U1 counterpart for splicing of U12-dependent introns, binds the NRS remarkably well and requires G-rich elements just downstream of the consensus U11 binding site.

Does the nature of the definitive impression material influence the outcome of (mandibular) complete dentures?

The effects of impression materials on the outcome of complete dentures are poorly understood. This double-blind cross-over randomized controlled trial investigated eleven adult edentulous patients. Each received a maxillary denture and three mandibular dentures (which differed only in the three materials used to record the definitive impressions).

Two regions promote U11 small nuclear ribonucleoprotein particle binding to a retroviral splicing inhibitor element (negative regulator of splicing).

The Rous sarcoma virus (RSV) negative regulator of splicing (NRS) is an RNA element that represses splicing and promotes polyadenylation of viral RNA. The NRS acts as a pseudo 5' splice site (ss), and serine-arginine (SR) proteins, U1snRNP, and U6 small nuclear ribonucleoproteins (snRNPs) are implicated in its function. The NRS also efficiently binds U11 snRNP of the U12-dependent splicing pathway, which is interesting, because U11 binds only poorly to authentic substrates that lack a U12-type 3' splice site.

Satisfaction with respite care: a pilot study.

Satisfaction with respite care may be bound up with a variety of factors. The interaction of social support with ratings of a carer's satisfaction with respite care has not been explored in published work. The present authors postulated that social support, both during caring and during periods of relief from caring whilst in receipt of respite care, would be associated with greater satisfaction with respite care.