Interpopulation hybridization results in widespread viability selection across the genome in Tigriopus californicus

<p>Abstract</p> <p>Background</p> <p>Genetic interactions within hybrids influence their overall fitness. Understanding the details of these interactions can improve our understanding of speciation. One experimental approach is to investigate deviations from Mendelian expectations (segregation distortion) in the inheritance of mapped genetic markers. In this study, we used the copepod <it>Tigriopus californicus</it>, a species which exhibits high genetic divergence between populations and a general pattern of reduced fitness in F2 interpopulation hybrids. Previous studies have implicated both nuclear-cytoplasmic and nuclear-nuclear interactions in causing this fitness reduction. We identified and mapped population-diagnostic single nucleotide polymorphisms (SNPs) and used these to examine segregation distortion across the genome within F2 hybrids.</p> <p>Results</p> <p>We generated a linkage map which included 45 newly elucidated SNPs and 8 population-diagnostic microsatellites used in previous studies. The map, the first available for the Copepoda, was estimated to cover 75% of the genome and included markers on all 12 <it>T. californicus </it>chromosomes. We observed little segregation distortion in newly hatched F2 hybrid larvae (fewer than 10% of markers at p < 0.05), but strikingly higher distortion in F2 hybrid adult males (45% of markers at p < 0.05). Hence, segregation distortion was primarily caused by selection against particular genetic combinations which acted between hatching and maturity. Distorted markers were not distributed randomly across the genome but clustered on particular chromosomes. In contrast to other studies in this species we found little evidence for cytonuclear coadaptation. Instead, different linkage groups exhibited markedly different patterns of distortion, which appear to have been influenced by nuclear-nuclear epistatic interactions and may also reflect genetic load carried within the parental lines.</p> <p>Conclusion</p> <p>Adult male F2 hybrids between two populations of <it>T. californius </it>exhibit dramatic segregation distortion across the genome. Distorted loci are clustered within specific linkage groups, and the direction of distortion differs between chromosomes. This segregation distortion is due to selection acting between hatching and adulthood.</p

Transposon Mutagenesis in Chlamydia trachomatis Identifies CT339 as a ComEC Homolog Important for DNA Uptake and Lateral Gene Transfer

Transposon mutagenesis is a widely applied and powerful genetic tool for the discovery of genes associated with selected phenotypes. Chlamydia trachomatis is a clinically significant, obligate intracellular bacterium for which many conventional genetic tools and capabilities have been developed only recently. This report describes the successful development and application of a Himar transposon mutagenesis system for generating single-insertion mutant clones of C. trachomatis. This system was used to generate a pool of 105 transposon mutant clones that included insertions in genes encoding flavin adenine dinucleotide (FAD)-dependent monooxygenase (C. trachomatis 148 [ct148]), deubiquitinase (ct868), and competence-associated (ct339) proteins. A subset of Tn mutant clones was evaluated for growth differences under cell culture conditions, revealing that most phenocopied the parental strain; however, some strains displayed subtle and yet significant differences in infectious progeny production and inclusion sizes. Bacterial burden studies in mice also supported the idea that a FAD-dependent monooxygenase (ct148) and a deubiquitinase (ct868) were important for these infections. The ct339 gene encodes a hypothetical protein with limited sequence similarity to the DNA-uptake protein ComEC. A transposon insertion in ct339 rendered the mutant incapable of DNA acquisition during recombination experiments. This observation, along with in situ structural analysis, supports the idea that this protein is playing a role in the fundamental process of lateral gene transfer similar to that of ComEC. In all, the development of the Himar transposon system for Chlamydia provides an effective genetic tool for further discovery of genes that are important for basic biology and pathogenesis aspects.S.D.L., Z.E.D., K.S.H., S.B., R.J.S., and P.S.H. were funded by NIH (AI126785)J.W. and P.S.H. were supported by NIH AI125929. P.S.H. was also supported by P20GM113117Support for genomic sequencing was supplemented by P20GM10363

Predictive genetic testing for Huntington's disease: Exploring participant experiences of uncertainty and ambivalence between clinic appointments

Ambivalence and uncertainty are key themes throughout the psychology of healthcare literature. This is especially so for individuals at risk of Huntington's disease (HD) deliberating the decision to undergo genetic testing because there is currently no treatment that modifies disease progression. A better understanding of the experience of making a decision about genetic prediction will help practitioners support and guide individuals through this process. Our aim was to capture participants' experiences of uncertainty and ambivalence in between their genetic counseling appointments. We explored these issues through the experiences of nine participants who were referred for predictive HD testing at four regional genetics services in England and Wales. Data consisted of recordings of clinic consultations, diaries, and an in‐depth interview conducted at the end of the testing process. Data were analyzed thematically. Four themes were identified representing four possible futures, each future dependent on the decision to undergo testing and the result of that test. Our results showed that participants, as well as attending more to a future that represents their current situation of not having undergone predictive testing, also attended more to a distant future where a positive predictive result is received and symptoms have started. Participants attended less to the two futures that were more immediate once testing was undertaken (a future where a positive result is received and symptoms have not started and a future where a negative result is received). The use of diaries gave us a unique insight into these participants' experiences of ambivalence and uncertainty, psychological distress, and the emotional burden experienced. These findings help inform discussions within the clinic appointment as well as encourage researchers to consider diary use as a method of exploring what happens for individuals outside of clinical encounters

Inclusion at Scale: Deploying a Community-Driven Moderation Intervention on Twitch

Harassment, especially of marginalized individuals, on networked gaming and social media platforms has been identified as a significant issue, yet few HCI practitioners have attempted to create interventions tackling toxicity online. Aligning ourselves with the growing cohort of design activists, we present a case study of the GLHF pledge, an interactive public awareness campaign promoting positivity in video game live streaming. We discuss the design and deployment of a community-driven moderation intervention for GLHF, intended to empower the inclusive communities emerging on Twitch. After offering a preliminary report on the effects we have observed based on the more than 370,000 gamers who have participated to date, the paper concludes with a reflection on the challenges and opportunities of using design activism to positively intervene in large-scale media platforms

Epigenetic change induced by in utero dietary challenge provokes phenotypic variability across multiple generations of mice

Transmission of epigenetic information between generations occurs in nematodes, flies and plants, mediated by specialised small RNA pathways, histone H3K9me3, H3K27me3, H4K16ac and DNA methylation 1-3 . In higher vertebrates, epidemiological and experimental evidence supports similar trans-generational effects 4,5 although the mechanisms that underpin these are incompletely understood 6-9 . We generated a luciferase reporter knock-in mouse for the imprinted Dlk1 locus, to visualise and track epigenetic fidelity across generations. We showed that exposure to high-fat diet (HFD) in pregnancy provokes sustained re-expression of the normally silent maternal Dlk1 allele in offspring, coincident with increased DNA methylation at the Dlk1 sDMR . Interestingly, maternal Dlk1 mis-expression was also evident in the next generation (F2), exclusively in animals derived from F1-exposed females. Oocytes from these females showed altered microRNA and gene expression, without any major changes in underlying DNA methylation, and correctly imprinted Dlk1 expression resumed in subsequent generations (F3 onwards). Our results reveal how canonical and non-canonical imprinting mechanisms enable the foetal epigenome to adapt to in utero challenge to modulate the properties of two successive generations of offspring

Culture and communication in ethically appropriate care

yesThis article considers the difficulties with using Gillon's model for health care ethics in the context of clinical practice. Everyday difficulties can arise when caring for people from different ethnic and cultural backgrounds, especially when they speak little or no English. A case is presented that establishes, owing to language and cultural barriers, that midwives may have difficulty in providing ethically appropriate care to women of Pakistani Muslim origin in the UK. The use of interpreters is discussed; however, there are limitations and counter arguments to their use. Training is identified as needed to prepare service providers and midwives for meeting the needs of a culturally diverse maternity population

It's not what you say but the way that you say it: an fMRI study of differential lexical and non-lexical prosodic pitch processing

<p>Abstract</p> <p>Background</p> <p>This study aims to identify the neural substrate involved in prosodic pitch processing. Functional magnetic resonance imaging was used to test the premise that prosody pitch processing is primarily subserved by the right cortical hemisphere.</p> <p>Two experimental paradigms were used, firstly pairs of spoken sentences, where the only variation was a single internal phrase pitch change, and secondly, a matched condition utilizing pitch changes within analogous tone-sequence phrases. This removed the potential confounder of lexical evaluation. fMRI images were obtained using these paradigms.</p> <p>Results</p> <p>Activation was significantly greater within the right frontal and temporal cortices during the tone-sequence stimuli relative to the sentence stimuli.</p> <p>Conclusion</p> <p>This study showed that pitch changes, stripped of lexical information, are mainly processed by the right cerebral hemisphere, whilst the processing of analogous, matched, lexical pitch change is preferentially left sided. These findings, showing hemispherical differentiation of processing based on stimulus complexity, are in accord with a 'task dependent' hypothesis of pitch processing.</p

A Review of Surgical Informed Consent: Past, Present, and Future. A Quest to Help Patients Make Better Decisions

Contains fulltext : 87422.pdf (publisher's version ) (Closed access)BACKGROUND: Informed consent (IC) is a process requiring a competent doctor, adequate transfer of information, and consent of the patient. It is not just a signature on a piece of paper. Current consent processes in surgery are probably outdated and may require major changes to adjust them to modern day legislation. A literature search may provide an opportunity for enhancing the quality of the surgical IC (SIC) process. METHODS: Relevant English literature obtained from PubMed, Picarta, PsycINFO, and Google between 1993 and 2009 was reviewed. RESULTS: The body of literature with respect to SIC is slim and of moderate quality. The SIC process is an underestimated part of surgery and neither surgeons nor patients sufficiently realize its importance. Surgeons are not specifically trained and lack the competence to guide patients through a legally correct SIC process. Computerized programs can support the SIC process significantly but are rarely used for this purpose. CONCLUSIONS: IC should be integrated into our surgical practice. Unfortunately, a big gap exists between the theoretical/legal best practice and the daily practice of IC. An optimally informed patient will have more realistic expectations regarding a surgical procedure and its associated risks. Well-informed patients will be more satisfied and file fewer legal claims. The use of interactive computer-based programs provides opportunities to improve the SIC process.1 juli 201