421 research outputs found
An effective strategy to diagnose HIV infection: findings from a national audit of HIV partner notification outcomes in sexual health and infectious disease clinics in the UK
The clinical effectiveness of the streamlined liner of pharyngeal airway (SLIPA™) compared with the laryngeal mask airway ProSeal™ during general anesthesia
Dispersal influences genetic and acoustic spatial structure for both males and females in a tropical songbird
Animals exhibit diverse dispersal strategies, including sex-biased dispersal, a phenomenon common in vertebrates. Dispersal influences the genetic structure of populations as well as geographic variation in phenotypic traits. Patterns of spatial genetic structure and geographic variation may vary between the sexes whenever males and females exhibit different dispersal behaviors. Here, we examine dispersal, spatial genetic structure, and spatial acoustic structure in Rufous-and-white Wrens, a year-round resident tropical bird. Both sexes sing in this species, allowing us to compare acoustic variation between males and females and examine the relationship between dispersal and song sharing for both sexes. Using a long-term dataset collected over an 11-year period, we used banding data and molecular genetic analyses to quantify natal and breeding dispersal distance in Rufous-and-white Wrens. We quantified song sharing and examined whether sharing varied with dispersal distance, for both males and females. Observational data and molecular genetic analyses indicate that dispersal is female-biased. Females dispersed farther from natal territories than males, and more often between breeding territories than males. Furthermore, females showed no significant spatial genetic structure, consistent with expectations, whereas males showed significant spatial genetic structure. Overall, natal dispersal appears to have more influence than breeding dispersal on spatial genetic structure and spatial acoustic structure, given that the majority of breeding dispersal events resulted in individuals moving only short distances. Song sharing between pairs of same-sex animals decreases with the distance between their territories for both males and females, although males exhibited significantly greater song sharing than females. Lastly, we measured the relationship between natal dispersal distance and song sharing. We found that sons shared fewer songs with their fathers the farther they dispersed from their natal territories, but that song sharing between daughters and mothers was not significantly correlated with natal dispersal distance. Our results reveal cultural differences between the sexes, suggesting a relationship between culture and sex-biased dispersal
Ethnicity and the first diagnosis of a wide range of cardiovascular diseases: Associations in a linked electronic health record cohort of 1 million patients
Background: While the association of ethnic group with individual cardiovascular diseases has been studied, little is known about ethnic differences in the initial lifetime presentation of clinical cardiovascular disease in contemporary populations. Methods and results: We studied 1,068,318 people, aged ≥30 years and free from diagnosed CVD at baseline (90.9% White, 3.6% South Asian and 2.9% Black), using English linked electronic health records covering primary care, hospital admissions, acute coronary syndrome registry and mortality registry (CALIBER research platform). During 5.7 years median follow-up between 1997-2010, 95,224 people experienced an incident cardiovascular diagnosis. 80.2% (77.7% -82.5%) of initial presentation in South Asian <60 yrs were coronary heart disease presentations compared to 66.2% (65.7-66.7) in White and 56.7% (52.1%-61.2%) in Black patients. Compared to White patients, Black patients had significantly lower age-sex adjusted hazard ratios (HRs) for initial lifetime presentation of all the coronary disease diagnoses (stable angina HR 0.80 (95% CI 0.68-0.93); unstable angina – 0.75 (0.59-0.97); myocardial infarction 0.49 (0.40-0.62)) while South Asian patients had significantly higher HRs (stable angina – 1.67 (1.52-1.84); unstable angina 1.82 (1.56-2.13); myocardial infarction – 1.67 (1.49-1.87). We found no ethnic differences in initial presentation with heart failure (Black 0.97 (0.79-1.20); S Asian 1.04(0.87-1.26)). Compared to White patients, Black patients were more likely to present with ischaemic stroke (1.24 (0.97-1.58)) and intracerebral haemorrhage (1.44 (0.97-2.12)). Presentation with peripheral arterial disease was less likely for Black (0.63 (0.50-0.80)) and South Asian patients (0.70 (0.57-0.86)) compared with White patients. Discussion: While we found the anticipated substantial predominance of coronary heart disease presentations in South Asian and predominance of stroke presentations in Black patients, we found no ethnic differences in presentation with heart failure. We consider the public health and research implications of our findings
Subgroup 4 R2R3-MYBs in conifer trees: gene family expansion and contribution to the isoprenoid- and flavonoid-oriented responses
Transcription factors play a fundamental role in plants by orchestrating temporal and spatial gene expression in response to environmental stimuli. Several R2R3-MYB genes of the Arabidopsis subgroup 4 (Sg4) share a C-terminal EAR motif signature recently linked to stress response in angiosperm plants. It is reported here that nearly all Sg4 MYB genes in the conifer trees Picea glauca (white spruce) and Pinus taeda (loblolly pine) form a monophyletic clade (Sg4C) that expanded following the split of gymnosperm and angiosperm lineages. Deeper sequencing in P. glauca identified 10 distinct Sg4C sequences, indicating over-represention of Sg4 sequences compared with angiosperms such as Arabidopsis, Oryza, Vitis, and Populus. The Sg4C MYBs share the EAR motif core. Many of them had stress-responsive transcript profiles after wounding, jasmonic acid (JA) treatment, or exposure to cold in P. glauca and P. taeda, with MYB14 transcripts accumulating most strongly and rapidly. Functional characterization was initiated by expressing the P. taeda MYB14 (PtMYB14) gene in transgenic P. glauca plantlets with a tissue-preferential promoter (cinnamyl alcohol dehydrogenase) and a ubiquitous gene promoter (ubiquitin). Histological, metabolite, and transcript (microarray and targeted quantitiative real-time PCR) analyses of PtMYB14 transgenics, coupled with mechanical wounding and JA application experiments on wild-type plantlets, allowed identification of PtMYB14 as a putative regulator of an isoprenoid-oriented response that leads to the accumulation of sesquiterpene in conifers. Data further suggested that PtMYB14 may contribute to a broad defence response implicating flavonoids. This study also addresses the potential involvement of closely related Sg4C sequences in stress responses and plant evolution
The structure of the KlcA and ArdB proteins reveals a novel fold and antirestriction activity against Type I DNA restriction systems in vivo but not in vitro
Plasmids, conjugative transposons and phage frequently encode anti-restriction proteins to enhance their chances of entering a new bacterial host that is highly likely to contain a Type I DNA restriction and modification (RM) system. The RM system usually destroys the invading DNA. Some of the anti-restriction proteins are DNA mimics and bind to the RM enzyme to prevent it binding to DNA. In this article, we characterize ArdB anti-restriction proteins and their close homologues, the KlcA proteins from a range of mobile genetic elements; including an ArdB encoded on a pathogenicity island from uropathogenic Escherichia coli and a KlcA from an IncP-1b plasmid, pBP136 isolated from Bordetella pertussis. We show that all the ArdB and KlcA act as anti-restriction proteins and inhibit the four main families of Type I RM systems in vivo, but fail to block the restriction endonuclease activity of the archetypal Type I RM enzyme, EcoKI, in vitro indicating that the action of ArdB is indirect and very different from that of the DNA mimics. We also present the structure determined by NMR spectroscopy of the pBP136 KlcA protein. The structure shows a novel protein fold and it is clearly not a DNA structural mimic
Non-Functional Parathyroid Carcinoma: A Review of the Literature and Report of a Case Requiring Extensive Surgery
Parathyroid carcinoma is a rare malignancy, and only accounts for 0.5–2% of cases of primary hyperparathyroidism. Less than 10% of parathyroid carcinomas are non-functional, and as such, they have been rarely reported in the literature. Importantly, margin status at resection is related to prognosis, and only a handful of case reports of non-functional carcinoma note this important parameter. Here we report the first case of non-functional parathyroid carcinoma with negative margins, and review the literature on this rare entity. Whether functional or non-functional, parathyroid carcinoma can often be difficult to differentiate from benign parathyroid adenoma. While diagnosis has been based on clinical and histological criteria, recent data concerning the molecular underpinnings of parathyroid carcinoma may allow for improved accuracy in distinguishing benign and malignant parathyroid tumors
Instrumentos de avaliação do aleitamento materno e seu uso na prática clínica
RESUMO Objetivos Identificar instrumentos de avaliação da amamentação e sua aplicação na prática clínica, validação e adaptação transcultural. Método Revisão integrativa, realizada em seis bases de dados e em uma biblioteca eletrônica, entre agosto/2014-dezembro/2015, sem limitação temporal. Resultados Foram identificados 19 instrumentos de avaliação do AM. Destes, 12 foram validados e cinco foram adaptados transculturalmente. Quanto à aplicação, destacam-se seu uso para a avaliação do risco de desmame (BAPT) e a percepção/comportamento da mulher em amamentar (BSES-SF e IIFAS). Conclusão A identificação dos instrumentos disponíveis e de suas indicações para a avaliação do AM pode auxiliar profissionais na escolha pelo instrumento a ser utilizado, qualificando a assistência materno-infantil
Rationally Designed Interfacial Peptides Are Efficient In Vitro Inhibitors of HIV-1 Capsid Assembly with Antiviral Activity
Virus capsid assembly constitutes an attractive target for the development of antiviral therapies; a few experimental inhibitors of this process for HIV-1 and other viruses have been identified by screening compounds or by selection from chemical libraries. As a different, novel approach we have undertaken the rational design of peptides that could act as competitive assembly inhibitors by mimicking capsid structural elements involved in intersubunit interfaces. Several discrete interfaces involved in formation of the mature HIV-1 capsid through polymerization of the capsid protein CA were targeted. We had previously designed a peptide, CAC1, that represents CA helix 9 (a major part of the dimerization interface) and binds the CA C-terminal domain in solution. Here we have mapped the binding site of CAC1, and shown that it substantially overlaps with the CA dimerization interface. We have also rationally modified CAC1 to increase its solubility and CA-binding affinity, and designed four additional peptides that represent CA helical segments involved in other CA interfaces. We found that peptides CAC1, its derivative CAC1M, and H8 (representing CA helix 8) were able to efficiently inhibit the in vitro assembly of the mature HIV-1 capsid. Cocktails of several peptides, including CAC1 or CAC1M plus H8 or CAI (a previously discovered inhibitor of CA polymerization), or CAC1M+H8+CAI, also abolished capsid assembly, even when every peptide was used at lower, sub-inhibitory doses. To provide a preliminary proof that these designed capsid assembly inhibitors could eventually serve as lead compounds for development of anti-HIV-1 agents, they were transported into cultured cells using a cell-penetrating peptide, and tested for antiviral activity. Peptide cocktails that drastically inhibited capsid assembly in vitro were also able to efficiently inhibit HIV-1 infection ex vivo. This study validates a novel, entirely rational approach for the design of capsid assembly interfacial inhibitors that show antiviral activity
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