Highly conserved gene order and numerous novel repetitive elements in genomic regions linked to wing pattern variation in Heliconius butterflies

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: With over 20 parapatric races differing in their warningly colored wing patterns, the butterfly Heliconius erato provides a fascinating example of an adaptive radiation. Together with matching races of its co-mimic Heliconius melpomene, H. erato also represents a textbook case of Müllerian mimicry, a phenomenon where common warning signals are shared amongst noxious organisms. It is of great interest to identify the specific genes that control the mimetic wing patterns of H. erato and H. melpomene. To this end we have undertaken comparative mapping and targeted genomic sequencing in both species. This paper reports on a comparative analysis of genomic sequences linked to color pattern mimicry genes in Heliconius. RESULTS: Scoring AFLP polymorphisms in H. erato broods allowed us to survey loci at approximately 362 kb intervals across the genome. With this strategy we were able to identify markers tightly linked to two color pattern genes: D and Cr, which were then used to screen H. erato BAC libraries in order to identify clones for sequencing. Gene density across 600 kb of BAC sequences appeared relatively low, although the number of predicted open reading frames was typical for an insect. We focused analyses on the D- and Cr-linked H. erato BAC sequences and on the Yb-linked H. melpomene BAC sequence. A comparative analysis between homologous regions of H. erato (Cr-linked BAC) and H. melpomene (Yb-linked BAC) revealed high levels of sequence conservation and microsynteny between the two species. We found that repeated elements constitute 26% and 20% of BAC sequences from H. erato and H. melpomene respectively. The majority of these repetitive sequences appear to be novel, as they showed no significant similarity to any other available insect sequences. We also observed signs of fine scale conservation of gene order between Heliconius and the moth Bombyx mori, suggesting that lepidopteran genome architecture may be conserved over very long evolutionary time scales. CONCLUSION: Here we have demonstrated the tractability of progressing from a genetic linkage map to genomic sequence data in Heliconius butterflies. We have also shown that fine-scale gene order is highly conserved between distantly related Heliconius species, and also between Heliconius and B. mori. Together, these findings suggest that genome structure in macrolepidoptera might be very conserved, and show that mapping and positional cloning efforts in different lepidopteran species can be reciprocally informative.The work was funded by U.S. National Science Foundation grants IOB 0344705 and DEB 0715096 to WOM. The H. erato BAC library was constructed by C. Wu, H. Zhang (TAMU), and M. R. Goldsmith (URI) under NSF Grant IBN-0208388. In addition, the Computational Biology Service Unit at Cornell University, which is partially funded by Microsoft Corporation, provided bioinformatics support for our analysis of genomic repeat structure. AFLP analysis and sequencing of PCR products was carried out at the Sequencing and Genotyping Center at the University of Puerto RicoRio Piedras. We thank Nicola Flanagan, Alexandra Tobler, Karla Maldonado, Jenny Acevedo Gonzales, Hector Alejandro Merchan, Yhadi Cotto, Kelitt Santiago and Felix Araujo Perez for help in rearing and maintaining butterfly stocks. Finally, a special thanks to Daniel P. Lindstrom for his support and helpful suggestions during manuscript preparation

Neutron Scattering and Its Application to Strongly Correlated Systems

Neutron scattering is a powerful probe of strongly correlated systems. It can directly detect common phenomena such as magnetic order, and can be used to determine the coupling between magnetic moments through measurements of the spin-wave dispersions. In the absence of magnetic order, one can detect diffuse scattering and dynamic correlations. Neutrons are also sensitive to the arrangement of atoms in a solid (crystal structure) and lattice dynamics (phonons). In this chapter, we provide an introduction to neutrons and neutron sources. The neutron scattering cross section is described and formulas are given for nuclear diffraction, phonon scattering, magnetic diffraction, and magnon scattering. As an experimental example, we describe measurements of antiferromagnetic order, spin dynamics, and their evolution in the La(2-x)Ba(x)CuO(4) family of high-temperature superconductors.Comment: 31 pages, chapter for "Strongly Correlated Systems: Experimental Techniques", edited by A. Avella and F. Mancin

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD

Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus

Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

Exploring the impact of CMIP5 model biases on the simulation of North Atlantic decadal variability

Instrumental observations, palaeo-proxies, and climate models suggest significant decadal variability within the North Atlantic subpolar gyre (NASPG). However, a poorly sampled observational record and a diversity of model behaviours mean that the precise nature and mechanisms of this variability are unclear. Here, we analyse an exceptionally large multi-model ensemble of 42 present-generation climate models to test whether NASPG mean state biases systematically affect the representation of decadal variability. Temperature and salinity biases in the Labrador Sea co-vary and influence whether density variability is controlled by temperature or salinity variations. Ocean horizontal resolution is a good predictor of the biases and the location of the dominant dynamical feedbacks within the NASPG. However, we find no link to the spectral characteristics of the variability. Our results suggest that the mean state and mechanisms of variability within the NASPG are not independent. This represents an important caveat for decadal predictions using anomaly-assimilation methods

Association of Fidaxomicin with C. difficile spores: Effects of Persistence on Subsequent Spore Recovery, Outgrowth and Toxin Production.

Background: We have previously shown that fidaxomicin instillation prevents spore recovery in an in-vitro gut model, whereas vancomycin does not. The reasons for this are unclear. Here, we have investigated persistence of fidaxomicin and vancomycin on C. difficile spores, and examined post-antibiotic exposure spore recovery, outgrowth and toxin production. Methods: Prevalent UK C. difficile ribotypes (n=10) were incubated with 200mg/L fidaxomicin, vancomycin or a non-antimicrobial containing control for 1 h in faecal filtrate or Phosphate Buffered Saline. Spores were washed three times with faecal filtrate or phosphate buffered saline, and residual spore-associated antimicrobial activity was determined by bioassay. For three ribotypes (027, 078, 015), antimicrobial-exposed, faecal filtrate-washed spores and controls were inoculated into broth. Viable vegetative and spore counts were enumerated on CCEYL agar. Percentage phase bright spores, phase dark spores and vegetative cells were enumerated by phase contrast microscopy at 0, 3, 6, 24 and 48 h post-inoculation. Toxin levels (24 and 48h) were determined by cell cytotoxicity assay. Results: Fidaxomicin, but not vancomycin persisted on spores of all ribotypes following washing in saline (mean=10.1mg/L; range= 4.0-14mg/L) and faecal filtrate (mean =17.4mg/L; 8.4-22.1mg/L). Outgrowth and proliferation rates of vancomycin-exposed spores were similar to controls, whereas fidaxomicin-exposed spores showed no vegetative cell growth after 24 and 48 h. At 48h, toxin levels averaged 3.7 and 3.3 relative units (RU) in control and vancomycin-exposed samples, respectively, but were undetectable in fidaxomicin-exposed samples. Conclusion: Fidaxomicin persists on C. difficile spores, whereas vancomycin does not. This persistence prevents subsequent growth and toxin production in vitro. This may have implications on spore viability, thereby impacting CDI recurrence and transmission rates

Competing mortality in patients diagnosed with bladder cancer: evidence of undertreatment in the elderly and female patients

Background: Bladder cancer (BC) predominantly affects the elderly and is often the cause of death among patients with muscleinvasive disease. Clinicians lack quantitative estimates of competing mortality risks when considering treatments for BC. Our aim was to determine the bladder cancer-specific mortality (CSM) rate and other-cause mortality (OCM) rate for patients with newly diagnosed BC. Methods: Patients (n ¼ 3281) identified from a population-based cancer registry diagnosed between 1994 and 2009. Median follow-up was 48.15 months (IQ range 18.1–98.7). Competing risk analysis was performed within patient groups and outcomes compared using Gray’s test. Results: At 5 years after diagnosis, 1246 (40%) patients were dead: 617 (19%) from BC and 629 (19%) from other causes. The 5-year BC mortality rate varied between 1 and 59%, and OCM rate between 6 and 90%, depending primarily on the tumour type and patient age. Cancer-specific mortality was highest in the oldest patient groups. Few elderly patients received radical treatment for invasive cancer (52% vs 12% for patients o60 vs 480 years, respectively). Female patients with high-risk non-muscle-invasive BC had worse CSM than equivalent males (Gray’s Po0.01). Conclusion: Bladder CSM is highest among the elderly. Female patients with high-risk tumours are more likely to die of their disease compared with male patients. Clinicians should consider offering more aggressive treatment interventions among older patients

Key epidemiological drivers and impact of interventions in the 2020 SARS-CoV-2 epidemic in England

We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Compared with other approaches, our model provides a synthesis of multiple surveillance data streams into a single coherent modelling framework allowing transmission and severity to be disentangled from features of the surveillance system. Of the control measures implemented, only national lockdown brought the reproduction number (Rteff ) below 1 consistently; if introduced one week earlier it could have reduced deaths in the first wave from an estimated 48,600 to 25,600 (95% credible interval [95%CrI]: 15,900-38,400). The infection fatality ratio decreased from 1.00% (95%CrI: 0.85%-1.21%) to 0.79% (95%CrI: 0.63%-0.99%), suggesting improved clinical care. The infection fatality ratio was higher in the elderly residing in care homes (23.3%, 95%CrI: 14.7%-35.2%) than those residing in the community (7.9%, 95%CrI: 5.9%-10.3%). On 2nd December 2020 England was still far from herd immunity, with regional cumulative infection incidence between 7.6% (95%CrI: 5.4%-10.2%) and 22.3% (95%CrI: 19.4%-25.4%) of the population. Therefore, any vaccination campaign will need to achieve high coverage and a high degree of protection in vaccinated individuals to allow non-pharmaceutical interventions to be lifted without a resurgence of transmission

Key epidemiological drivers and impact of interventions in the 2020 SARS-CoV-2 epidemic in England

We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Compared with other approaches, our model provides a synthesis of multiple surveillance data streams into a single coherent modelling framework allowing transmission and severity to be disentangled from features of the surveillance system. Of the control measures implemented, only national lockdown brought the reproduction number (Rteff ) below 1 consistently; if introduced one week earlier it could have reduced deaths in the first wave from an estimated 48,600 to 25,600 (95% credible interval [95%CrI]: 15,900-38,400). The infection fatality ratio decreased from 1.00% (95%CrI: 0.85%-1.21%) to 0.79% (95%CrI: 0.63%-0.99%), suggesting improved clinical care. The infection fatality ratio was higher in the elderly residing in care homes (23.3%, 95%CrI: 14.7%-35.2%) than those residing in the community (7.9%, 95%CrI: 5.9%-10.3%). On 2nd December 2020 England was still far from herd immunity, with regional cumulative infection incidence between 7.6% (95%CrI: 5.4%-10.2%) and 22.3% (95%CrI: 19.4%-25.4%) of the population. Therefore, any vaccination campaign will need to achieve high coverage and a high degree of protection in vaccinated individuals to allow non-pharmaceutical interventions to be lifted without a resurgence of transmission