Gaps in detailed knowledge of human papillomavirus (HPV) and the HPV vaccine among medical students in Scotland

<p>Background: A vaccination programme targeted against human papillomavirus (HPV) types16 and 18 was introduced in the UK in 2008, with the aim of decreasing incidence of cervical disease. Vaccine roll out to 12–13 year old girls with a catch-up programme for girls aged up to 17 years and 364 days was accompanied by a very comprehensive public health information (PHI) campaign which described the role of HPV in the development of cervical cancer.</p> <p>Methods: A brief questionnaire, designed to assess acquisition of knowledge of HPV infection and its association to cervical cancer, was administered to two different cohorts of male and female 1st year medical students (school leavers: 83% in age range 17–20) at a UK university. The study was timed so that the first survey in 2008 immediately followed a summer's intensive PHI campaign and very shortly after vaccine roll-out (150 students). The second survey was exactly one year later over which time there was a sustained PHI campaign (213 students).</p> <p>Results: We addressed three research questions: knowledge about three specific details of HPV infection that could be acquired from PHI, whether length of the PHI campaign and/or vaccination of females had any bearing on HPV knowledge, and knowledge differences between men and women regarding HPV. No female student in the 2008 cohort had completed the three-dose vaccine schedule compared to 58.4% of female students in 2009. Overall, participants’ knowledge regarding the sexually transmitted nature of HPV and its association with cervical cancer was high in both year groups. However, in both years, less than 50% of students correctly identified that HPV causes over 90% of cases of cervical cancer. Males gave fewer correct answers for these two details in 2009. In 2008 only around 50% of students recognised that the current vaccine protects against a limited subset of cervical cancer-causing HPV sub-types, although there was a significant increase in correct response among female students in the 2009 cohort compared to the 2008 cohort.</p> <p>onclusions: This study highlights a lack of understanding regarding the extent of protection against cervical cancer conferred by the HPV vaccine, even among an educated population in the UK who could have a vested interest in acquiring such knowledge. The intensive PHI campaign accompanying the first year of HPV vaccination seemed to have little effect on knowledge over time. This is one of the first studies to assess detailed knowledge of HPV in both males and females. There is scope for continued improvements to PHI regarding the link between HPV infection and cervical cancer.</p&gt

Dynamic biospeckle analysis, a new tool for the fast screening of plant nematicide selectivity

Background: Plant feeding, free-living nematodes cause extensive damage to plant roots by direct feeding and, in the case of some trichodorid and longidorid species, through the transmission of viruses. Developing more environmentally friendly, target-specific nematicides is currently impeded by slow and laborious methods of toxicity testing. Here, we developed a bioactivity assay based on the dynamics of light 'speckle' generated by living cells and we demonstrate its application by assessing chemicals' toxicity to different nematode trophic groups.Results: Free-living nematode populations extracted from soil were exposed to methanol and phenyl isothiocyanate (PEITC). Biospeckle analysis revealed differing behavioural responses as a function of nematode feeding groups. Trichodorus nematodes were less sensitive than were bacterial feeding nematodes or non-trichodorid plant feeding nematodes. Following 24 h of exposure to PEITC, bioactivity significantly decreased for plant and bacterial feeders but not for Trichodorus nematodes. Decreases in movement for plant and bacterial feeders in the presence of PEITC also led to measurable changes to the morphology of biospeckle patterns.Conclusions: Biospeckle analysis can be used to accelerate the screening of nematode bioactivity, thereby providing a fast way of testing the specificity of potential nematicidal compounds. With nematodes' distinctive movement and activity levels being visible in the biospeckle pattern, the technique has potential to screen the behavioural responses of diverse trophic nematode communities. The method discriminates both behavioural responses, morphological traits and activity levels and hence could be used to assess the specificity of nematicidal compounds.</p

D-branes at Toric Singularities: Model Building, Yukawa Couplings and Flavour Physics

We discuss general properties of D-brane model building at toric singularities. Using dimer techniques to obtain the gauge theory from the structure of the singularity, we extract results on the matter sector and superpotential of the corresponding gauge theory. We show that the number of families in toric phases is always less than or equal to three, with a unique exception being the zeroth Hirzebruch surface. With the physical input of three generations we find that the lightest family of quarks is massless and the masses of the other two can be hierarchically separated. We compute the CKM matrix for explicit models in this setting and find the singularities possess sufficient structure to allow for realistic mixing between generations and CP violation.Comment: 55 pages, v2: typos corrected, minor comments adde

Genomic signatures of domestication on neurogenetic genes in Drosophila melanogaster

© 2016 Stanley and Kulathinal. Background: Domesticated animals quickly evolve docile and submissive behaviors after isolation from their wild conspecifics. Model organisms reared for prolonged periods in the laboratory also exhibit similar shifts towards these domesticated behaviors. Yet whether this divergence is due to inadvertent selection in the lab or the fixation of deleterious mutations remains unknown. Results: Here, we compare the genomes of lab-reared and wild-caught Drosophila melanogaster to understand the genetic basis of these recently endowed behaviors common to laboratory models. From reassembled genomes of common lab strains, we identify unique, derived variants not present in global populations (lab-specific SNPs). Decreased selective constraints across low frequency SNPs (unique to one or two lab strains) are different from patterns found in the wild and more similar to neutral expectations, suggesting an overall accumulation of deleterious mutations. However, high-frequency lab SNPs found in most or all lab strains reveal an enrichment of X-linked loci and neuro-sensory genes across large extended haplotypes. Among shared polymorphisms, we also find highly differentiated SNPs, in which the derived allele is higher in frequency in the wild (Fstwild>lab), enriched for similar neurogenetic ontologies, indicative of relaxed selection on more active wild alleles in the lab. Conclusions: Among random mutations that continuously accumulate in the laboratory, we detect common adaptive signatures in domesticated lab strains of fruit flies. Our results demonstrate that lab animals can quickly evolve domesticated behaviors via unconscious selection by humans early on a broad pool of disproportionately large neurogenetic targets followed by the fixation of accumulated deleterious mutations on functionally similar targets

flyDIVaS: A comparative genomics resource for Drosophila divergence and selection

© 2016 Stanley and Kulathinal. With arguably the best finished and expertly annotated genome assembly, Drosophila melanogaster is a formidable genetics model to study all aspects of biology. Nearly a decade ago, the 12 Drosophila genomes project expanded D. melanogaster's breadth as a comparative model through the community-development of an unprecedented genus- and genome-wide comparative resource. However, since its inception, these datasets for evolutionary inference and biological discovery have become increasingly outdated, outmoded, and inaccessible. Here, we provide an updated and upgradable comparative genomics resource of Drosophila divergence and selection, flyDIVaS, based on the latest genomic assemblies, curated FlyBase annotations, and recent OrthoDB orthology calls. flyDIVaS is an online database containing D. melanogaster-centric orthologous gene sets, CDS and protein alignments, divergence statistics (% gaps, dN, dS, dN/dS), and codon-based tests of positive Darwinian selection. Out of 13,920 protein-coding D. melanogaster genes, ~80% have one aligned ortholog in the closely related species, D. simulans, and ~50% have 1-1 12-way alignments in the original 12 sequenced species that span over 80 million yr of divergence. Genes and their orthologs can be chosen from four different taxonomic datasets differing in phylogenetic depth and coverage density, and visualized via interactive alignments and phylogenetic trees. Users can also batch download entire comparative datasets. A functional survey finds conserved mitotic and neural genes, highly diverged immune and reproduction-related genes, more conspicuous signals of divergence across tissue-specific genes, and an enrichment of positive selection among highly diverged genes. flyDIVaS will be regularly updated and can be freely accessed at www. flydivas.info. We encourage researchers to regularly use this resource as a tool for biological inference and discovery, and in their classrooms to help train the next generation of biologists to creatively use such genomic big data resources in an integrative manner

Neurogenomics and the role of a large mutational target on rapid behavioral change

© 2016 The Author(s). Background: Behavior, while complex and dynamic, is among the most diverse, derived, and rapidly evolving traits in animals. The highly labile nature of heritable behavioral change is observed in such evolutionary phenomena as the emergence of converged behaviors in domesticated animals, the rapid evolution of preferences, and the routine development of ethological isolation between diverging populations and species. In fact, it is believed that nervous system development and its potential to evolve a seemingly infinite array of behavioral innovations played a major role in the successful diversification of metazoans, including our own human lineage. However, unlike other rapidly evolving functional systems such as sperm-egg interactions and immune defense, the genetic basis of rapid behavioral change remains elusive. Presentation of the hypothesis: Here we propose that the rapid divergence and widespread novelty of innate and adaptive behavior is primarily a function of its genomic architecture. Specifically, we hypothesize that the broad diversity of behavioral phenotypes present at micro- and macroevolutionary scales is promoted by a disproportionately large mutational target of neurogenic genes. We present evidence that these large neuro-behavioral targets are significant and ubiquitous in animal genomes and suggest that behavior's novelty and rapid emergence are driven by a number of factors including more selection on a larger pool of variants, a greater role of phenotypic plasticity, and/or unique molecular features present in large genes. We briefly discuss the origins of these large neurogenic genes, as they relate to the remarkable diversity of metazoan behaviors, and highlight key consequences on both behavioral traits and neurogenic disease across, respectively, evolutionary and ontogenetic time scales. Testing the hypothesis: Current approaches to studying the genetic mechanisms underlying rapid phenotypic change primarily focus on identifying signatures of Darwinian selection in protein-coding regions. In contrast, the large mutational target hypothesis places genomic architecture and a larger allelic pool at the forefront of rapid evolutionary change, particularly in genetic systems that are polygenic and regulatory in nature. Genomic data from brain and neural tissues in mammals as well as a preliminary survey of neurogenic genes from comparative genomic data support this hypothesis while rejecting both positive and relaxed selection on proteins or higher mutation rates. In mammals and invertebrates, neurogenic genes harbor larger protein-coding regions and possess a richer regulatory repertoire of miRNA targets and transcription factor binding sites. Overall, neurogenic genes cover a disproportionately large genomic fraction, providing a sizeable substrate for evolutionary, genetic, and molecular mechanisms to act upon. Readily available comparative and functional genomic data provide unexplored opportunities to test whether a distinct neurogenomic architecture can promote rapid behavioral change via several mechanisms unique to large genes, and which components of this large footprint are uniquely metazoan. Implications of the hypothesis: The large mutational target hypothesis highlights the eminent roles of mutation and functional genomic architecture in generating rapid developmental and evolutionary change. It has broad implications on our understanding of the genetics of complex adaptive traits such as behavior by focusing on the importance of mutational input, from SNPs to alternative transcripts to transposable elements, on driving evolutionary rates of functional systems. Such functional divergence has important implications in promoting behavioral isolation across short- and long-term timescales. Due to genome-scaled polygenic adaptation, the large target effect also contributes to our inability to identify adapted behavioral candidate genes. The presence of large neurogenic genes, particularly in the mammalian brain and other neural tissues, further offers emerging insight into the etiology of neurodevelopmental and neurodegenerative diseases. The well-known correlation between neurological spectrum disorders in children and paternal age may simply be a direct result of aging fathers accumulating mutations across these large neurodevelopmental genes. The large mutational target hypothesis can also explain the rapid evolution of other functional systems covering a large genomic fraction such as male fertility and its preferential association with hybrid male sterility among closely related taxa. Overall, a focus on mutational potential may increase our power in understanding the genetic basis of complex phenotypes such as behavior while filling a general gap in understanding their evolution

The emergence of synaesthesia in a Neuronal Network Model via changes in perceptual sensitivity and plasticity

Synaesthesia is an unusual perceptual experience in which an inducer stimulus triggers a percept in a different domain in addition to its own. To explore the conditions under which synaesthesia evolves, we studied a neuronal network model that represents two recurrently connected neural systems. The interactions in the network evolve according to learning rules that optimize sensory sensitivity. We demonstrate several scenarios, such as sensory deprivation or heightened plasticity, under which synaesthesia can evolve even though the inputs to the two systems are statistically independent and the initial cross-talk interactions are zero. Sensory deprivation is the known causal mechanism for acquired synaesthesia and increased plasticity is implicated in developmental synaesthesia. The model unifies different causes of synaesthesia within a single theoretical framework and repositions synaesthesia not as some quirk of aberrant connectivity, but rather as a functional brain state that can emerge as a consequence of optimising sensory information processing

Combining microfluidics and RNA-sequencing to assess the inducible defensome of a mushroom against nematodes

Background Fungi are an attractive source of nutrients for predators. As part of their defense, some fungi are able to induce the production of anti-predator protein toxins in response to predation. A previous study on the interaction of the model mushroom Coprinopsis cinerea by the fungivorous nematode Aphelenchus avenae on agar plates has shown that the this fungal defense response is most pronounced in the part of the mycelium that is in direct contact with the nematode. Hence, we hypothesized that, for a comprehensive characterization of this defense response, an experimental setup that maximizes the zone of direct interaction between the fungal mycelium and the nematode, was needed. Results In this study, we conducted a transcriptome analysis of C. cinerea vegetative mycelium upon challenge with A. avenae using a tailor-made microfluidic device. The device was designed such that the interaction between the fungus and the nematode was confined to a specific area and that the mycelium could be retrieved from this area for analysis. We took samples from the confrontation area after different time periods and extracted and sequenced the poly(A)+ RNA thereof. The identification of 1229 differentially expressed genes (DEGs) shows that this setup profoundly improved sensitivity over co-cultivation on agar plates where only 37 DEGs had been identified. The product of one of the most highly upregulated genes shows structural homology to bacterial pore-forming toxins, and revealed strong toxicity to various bacterivorous nematodes. In addition, bacteria associated with the fungivorous nematode A. avenae were profiled with 16S rRNA deep sequencing. Similar to the bacterivorous and plant-feeding nematodes, Proteobacteria and Bacteroidetes were the most dominant phyla in A. avenae. Conclusions The use of a novel experimental setup for the investigation of the defense response of a fungal mycelium to predation by fungivorous nematodes resulted in the identification of a comprehensive set of DEGs and the discovery of a novel type of fungal defense protein against nematodes. The bacteria found to be associated with the fungivorous nematode are a possible explanation for the induction of some antibacterial defense proteins upon nematode challenge

Probing bacterial-fungal interactions at the single cell level.

Interactions between fungi and prokaryotes are abundant in many ecological systems. A wide variety of biomolecules regulate such interactions and many of them have found medicinal or biotechnological applications. However, studying a fungal-bacterial system at a cellular level is technically challenging. New microfluidic devices provided a platform for microscopic studies and for long-term, time-lapse experiments. Application of these novel tools revealed insights into the dynamic interactions between the basidiomycete Coprinopsis cinerea and the bacterium Bacillus subtilis. Direct contact was mediated by polar attachment of bacteria to only a subset of fungal hyphae suggesting a differential competence of fungal hyphae and thus differentiation of hyphae within a mycelium. The fungicidal activity of B. subtilis was monitored at a cellular level and showed a novel mode of action on fungal hyphae

Circular to the Magistracy of Van Diemen's Land from His Excellency Sir William Denison, with a view to obtain an expression of the views of the colonists on the subject of transportation to that colony from the Private Secretary's Office, Government House, March, 1847 - addressed to Frederick A Downing, with draft reply.

Circular from His Excellency Sir William Denison, addressed to the Magistracy of Van Diemen's Land, with a view to obtain an expression of the views of the colonists on the subject of transportation to that colony. His Excellency has thought it desirable to take this mode of ascertaining the views of the inhabitants of the colony on this very important question, in order that he may be in the position to lay before the Secretary of State, a clear statement of the views and wishes of the colonists. The questions asked were: 1. Do you consider it desirable that the transportation of convicts to this country should cease altogether? 2. If you think it desirable that convicts should still continue to be transported to this colony, but in reduced numbers, what number should you consider would be adequate to the wants of the country, in order to keep up a proper supply of labour ? and 3. You are requested to state what alterations in the regulations respecting the hiring of passholders are desirable, with a view to rendering the labour of the convict of more benefit to his employer, keeping in view at the same time the necessity of encouraging habits of industry, steadiness, and regularity of conduct in the convicts. Reply to (Sir R Denison, Governor)the circular questions is written by Captain C Stanley, (Private Secretary) on behalf of Frederick A Downing Esq., Hobart Town, 10th May 1847. RS.131/