Bridging the gap between social tagging and semantic annotation: E.D. the Entity Describer

Semantic annotation enables the development of efficient computational methods for analyzing and interacting with information, thus maximizing its value. With the already substantial and constantly expanding data generation capacity of the life sciences as well as the concomitant increase in the knowledge distributed in scientific articles, new ways to produce semantic annotations of this information are crucial. While automated techniques certainly facilitate the process, manual annotation remains the gold standard in most domains. In this manuscript, we describe a prototype mass-collaborative semantic annotation system that, by distributing the annotation workload across the broad community of biomedical researchers, may help to produce the volume of meaningful annotations needed by modern biomedical science. We present E.D., the Entity Describer, a mashup of the Connotea social tagging system, an index of semantic web-accessible controlled vocabularies, and a new public RDF database for storing social semantic annotations

Human cytomegalovirus: taking the strain

In celebrating the 60th anniversary of the first isolation of human cytomegalovirus (HCMV), we reflect on the merits and limitations of the viral strains currently being used to develop urgently needed treatments. HCMV research has been dependent for decades on the high-passage strains AD169 and Towne, heavily exploiting their capacity to replicate efficiently in fibroblasts. However, the genetic integrity of these strains is so severely compromised that great caution needs to be exercised when considering their past and future use. It is now evident that wild-type HCMV strains are not readily propagated in vitro. HCMV mutants are rapidly selected during isolation in fibroblasts, reproducibly affecting gene RL13, the UL128 locus (which includes genes UL128, UL130 and UL131A) and often the UL/b′ region. As a result, the virus becomes less cell associated, altered in tropism and less pathogenic. This problem is not restricted to high-passage strains, as even low-passage strains can harbour biologically significant mutations. Cloning and manipulation of the HCMV genome as a bacterial artificial chromosome (BAC) offers a means of working with stable, genetically defined strains. To this end, the low-passage strain Merlin genome was cloned as a BAC and sequentially repaired to match the viral sequence in the original clinical sample from which Merlin was derived. Restoration of UL128L to wild type was detrimental to growth in fibroblasts, whereas restoration of RL13 impaired growth in all cell types tested. Stable propagation of phenotypically wild-type virus could be achieved only by placing both regions under conditional expression. In addition to the development of these tools, the Merlin transcriptome and proteome have been characterized in unparalleled detail. Although Merlin may be representative of the clinical agent, high-throughput whole-genome deep sequencing studies have highlighted the remarkable high level of interstrain variation present in circulating virus. There is a need to develop systems capable of addressing the significance of this diversity, free from the confounding effects of genetic changes associated with in vitro adaptation. The generation of a set of BAC clones, each containing the genome of a different HCMV strain repaired to match the sequence in the clinical sample, would provide a pathway to address the biological and clinical effects of natural variation in wild-type HCMV

Regulation of AUXIN RESPONSE FACTOR condensation and nucleo-cytoplasmic partitioning

Auxin critically regulates plant growth and development. Auxin-driven transcriptional responses are mediated through the AUXIN RESPONSE FACTOR (ARF) family of transcription factors. ARF protein condensation attenuates ARF activity, resulting in dramatic shifts in the auxin transcriptional landscape. Here, we perform a forward genetics screen for ARF hypercondensation, identifying an F-box protein, which we named AUXIN RESPONSE FACTOR F-BOX1 (AFF1). Functional characterization of SC

Observation of interference fringes in Autler-Townes line shapes

Journals published by the American Physical Society can be found at http://publish.aps.org/We observe Ramsey fringes in the absorption line shape for a weak optical field probing the transition between an unperturbed quantum state and one that is dynamically Stark shifted by a strong pump field

How do the prevalence and relative risk of non-suicidal self-injury and suicidal thoughts vary across the population distribution of common mental distress (the p factor)? Observational analyses replicated in two independent UK cohorts of young people

Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Objectives: To inform suicide prevention policies and responses to youths at risk by investigating whether suicide risk is predicted by a summary measure of common mental distress (CMD (the p factor)) as well as by conventional psychopathological domains; to define the distribution of suicide risks over the population range of CMD; to test whether such distress mediates the medium-term persistence of suicide risks. Design: Two independent population-based cohorts. Setting: Population based in two UK centres. Participants: Volunteers aged 14–24 years recruited from primary healthcare registers, schools and colleges, with advertisements to complete quotas in age-sex-strata. Cohort 1 is the Neuroscience in Psychiatry Network (n=2403); cohort 2 is the ROOTS sample (n=1074). Primary outcome measures: Suicidal thoughts (ST) and non-suicidal self-injury (NSSI). Results: We calculated a CMD score using confirmatory bifactor analysis and then used logistic regressions to determine adjusted associations between risks and CMD; curve fitting was used to examine the relative prevalence of STs and NSSI over the population distribution of CMD. We found a dose–response relationship between levels of CMD and risk of suicide. The majority of all subjects experiencing ST and NSSI (78% and 76% in cohort 1, and 66% and 71% in cohort 2) had CMD scores no more than 2 SDs above the population mean; higher scores indicated the highest risk but were, by definition, infrequent. Pathway mediation models showed that CMD mediated the longitudinal course of both ST and NSSI. Conclusions: NSSI and ST in youths reflect CMD that also mediates their persistence. Universal prevention strategies reducing levels of CMD in the whole population without recourse to screening or measurement may prevent more suicides than approaches targeting youths with the most severe distress or with psychiatric disorders

Simplified RNA secondary structure mapping by automation of SHAPE data analysis

SHAPE (Selective 2′-hydroxyl acylation analysed by primer extension) technology has emerged as one of the leading methods of determining RNA secondary structure at the nucleotide level. A significant bottleneck in using SHAPE is the complex and time-consuming data processing that is required. We present here a modified data collection method and a series of algorithms, embodied in a program entitled Fast Analysis of SHAPE traces (FAST), which significantly reduces processing time. We have used this method to resolve the secondary structure of the first ∼900 nt of the hepatitis C virus (HCV) genome, including the entire core gene. We have also demonstrated the ability of SHAPE/FAST to detect the binding of a small molecule inhibitor to the HCV internal ribosomal entry site (IRES). In conclusion, FAST allows for high-throughput data processing to match the current high-throughput generation of data possible with SHAPE, reducing the barrier to determining the structure of RNAs of interest

Women’s experiences of receiving care for pelvic organ prolapse: a qualitative study

Background Pelvic organ prolapse is a common urogenital condition affecting 41–50% of women over the age of 40. To achieve early diagnosis and appropriate treatment, it is important that care is sensitive to and meets women’s needs, throughout their patient journey. This study explored women’s experiences of seeking diagnosis and treatment for prolapse and their needs and priorities for improving person-centred care. Methods Twenty-two women receiving prolapse care through urogynaecology services across three purposefully selected NHS UK sites took part in three focus groups and four telephone interviews. A topic guide facilitated discussions about women’s experiences of prolapse, diagnosis, treatment, follow-up, interactions with healthcare professionals, overall service delivery, and ideals for future services to meet their needs. Data were analysed thematically. Results Three themes emerged relating to women’s experiences of a) Evaluating what is normal b) Hobson’s choice of treatment decisions, and c) The trial and error of treatment and technique. Women often delayed seeking help for their symptoms due to lack of awareness, embarrassment and stigma. When presented to GPs, their symptoms were often dismissed and unaddressed until they became more severe. Women reported receiving little or no choice in treatment decisions. Choices were often influenced by health professionals’ preferences which were subtly reflected through the framing of the offer. Women’s embodied knowledge of their condition and treatment was largely unheeded, resulting in decisions that were inconsistent with women’s preferences and needs. Physiotherapy based interventions were reported as helping women regain control over their symptoms and life. A need for greater awareness of prolapse and physiotherapy interventions among women, GPs and consultants was identified alongside greater focus on prevention, early diagnosis and regular follow-up. Greater choice and involvement in treatment decision making was desired. Conclusions As prolapse treatment options expand to include more conservative choices, greater awareness and education is needed among women and professionals about these as a first line treatment and preventive measure, alongside a multi-professional team approach to treatment decision making. Women presenting with prolapse symptoms need to be listened to by the health care team, offered better information about treatment choices, and supported to make a decision that is right for them