CDK control pathways integrate cell size and ploidy information to control cell division

Maintenance of cell size homeostasis is a property that is conserved throughout eukaryotes. Cell size homeostasis is brought about by the co-ordination of cell division with cell growth and requires restriction of smaller cells from undergoing mitosis and cell division, whilst allowing larger cells to do so. Cyclin-CDK is the fundamental driver of mitosis and therefore ultimately ensures size homeostasis. Here we dissect determinants of CDK activity in vivo to investigate how cell size information is processed by the cell cycle network in fission yeast. We develop a high-throughput single-cell assay system of CDK activity in vivo and show that inhibitory tyrosine phosphorylation of CDK encodes cell size information, with the phosphatase PP2A aiding to set a size threshold for division. CDK inhibitory phosphorylation works synergistically with PP2A to prevent mitosis in smaller cells. Finally, we find that diploid cells of equivalent size to haploid cells exhibit lower CDK activity in response to equal cyclin-CDK enzyme concentrations, suggesting that CDK activity is reduced by increased DNA levels. Therefore, scaling of cyclin-CDK levels with cell size, CDK inhibitory phosphorylation, PP2A, and DNA-dependent inhibition of CDK activity, all inform the cell cycle network of cell size, thus contributing to cell size homeostasis

Application of Big Data to Support Evidence-Based Public Health Policy Decision-Making for Hearing

Ideally, public health policies are formulated from scientific data; however, policy-specific data are often unavailable. Big data can generate ecologically-valid, high-quality scientific evidence, and therefore has the potential to change how public health policies are formulated. Here, we discuss the use of big data for developing evidence-based hearing health policies, using data collected and analyzed with a research prototype of a data repository known as EVOTION (EVidence-based management of hearing impairments: public health pOlicy-making based on fusing big data analytics and simulaTION), to illustrate our points. Data in the repository consist of audiometric clinical data, prospective real-world data collected from hearing aids and an app, and responses to questionnaires collected for research purposes. To date, we have used the platform and a synthetic dataset to model the estimated risk of noise-induced hearing loss and have shown novel evidence of ways in which external factors influence hearing aid usage patterns. We contend that this research prototype data repository illustrates the value of using big data for policy-making by providing high-quality evidence that could be used to formulate and evaluate the impact of hearing health care policies

Chaos game representation for comparison of whole genomes

BACKGROUND: Chaos game representation of genome sequences has been used for visual representation of genome sequence patterns as well as alignment-free comparisons of sequences based on oligonucleotide frequencies. However the potential of this representation for making alignment-based comparisons of whole genome sequences has not been exploited. RESULTS: We present here a fast algorithm for identifying all local alignments between two long DNA sequences using the sequence information contained in CGR points. The local alignments can be depicted graphically in a dot-matrix plot or in text form, and the significant similarities and differences between the two sequences can be identified. We demonstrate the method through comparison of whole genomes of several microbial species. Given two closely related genomes we generate information on mismatches, insertions, deletions and shuffles that differentiate the two genomes. CONCLUSION: Addition of the possibility of large scale sequence alignment to the repertoire of alignment-free sequence analysis applications of chaos game representation, positions CGR as a powerful sequence analysis tool

Drift, not selection, shapes toll-like receptor variation among oceanic island populations

Understanding the relative role of different evolutionary forces in shaping the level and distribution of functional genetic diversity among natural populations is a key issue in evolutionary and conservation biology. To do so accurately genetic data must be analyzed in conjunction with an unambiguous understanding of the historical processes that have acted upon the populations. Here we focused on diversity at toll-like receptor (TLR) loci, which play a key role in the vertebrate innate immune system and, therefore, are expected to be under pathogen-mediated selection. We assessed TLR variation within and among 13 island populations (grouped into three archipelagos) of Berthelot's pipit, Anthus berthelotii, for which detailed population history has previously been ascertained. We also compared the variation observed with that found in its widespread sister species, the tawny pipit, Anthus campestris. We found strong evidence for positive selection at specific codons in TLR1LA, TLR3 and TLR4. Despite this, we found that at the allele frequency level, demographic history has played the major role in shaping patterns of TLR variation in Berthelot's pipit. Levels of diversity and differentiation within and across archipelagos at all TLR loci corresponded very closely with neutral microsatellite variation, and with the severity of the bottlenecks that occurred during colonization. Our study shows that despite the importance of TLRs in combating pathogens, demography can be the main driver of immune gene variation within and across populations, resulting in patterns of functional variation that can persist over evolutionary timescales. This article is protected by copyright. All rights reserved

Hierarchically modelling Kepler dwarfs and subgiants to improve inference of stellar properties with asteroseismology

This work is a part of a project that has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (CartographY; grant agreement ID 804752). AJL, GRD, and WJC acknowledge the support of the Science and Technology Facilities Council. DH acknowledges support from the Alfred P. Sloan Foundation, the National Aeronautics and Space Administration (80NSSC19K0597), and the National Science Foundation (AST-1717000). MBN acknowledges support from the UK Space Agency. RAG acknowledges the funding from the PLATO CNES grant.With recent advances in modelling stars using high-precision asteroseismology, the systematic effects associated with our assumptions of stellar helium abundance (Y) and the mixing-length theory parameter (αMLT) are becoming more important. We apply a new method to improve the inference of stellar parameters for a sample of Kepler dwarfs and subgiants across a narrow mass range (⁠0.8<M<1.2M⊙). In this method, we include a statistical treatment of Y and the αMLT. We develop a hierarchical Bayesian model to encode information about the distribution of Y and αMLT in the population, fitting a linear helium enrichment law including an intrinsic spread around this relation and normal distribution in αMLT. We test various levels of pooling parameters, with and without solar data as a calibrator. When including the Sun as a star, we find the gradient for the enrichment law, ΔY/ΔZ=1.05+0.28−0.25 and the mean αMLT in the population, μα=1.90+0.10−0.09, μα=1.90+0.10−0.09⁠. While accounting for the uncertainty in Y and αMLT, we are still able to report statistical uncertainties of 2.5 per cent in mass, 1.2 per cent in radius, and 12 per cent in age. Our method can also be applied to larger samples that will lead to improved constraints on both the population level inference and the star-by-star fundamental parameters.Publisher PDFPeer reviewe

Characterisation and evaluation of the impact of microfabricated pockets on the performance of limbal epithelial stem cells in biodegradable PLGA membranes for corneal regeneration

Scarring of the cornea affects thousands of people every year, significantly reducing the quality of life and potentially leading to corneal blindness. Although cultured limbal epithelial cells have been used to regenerate scarred corneas for more than 15 years, the culture strategies do not deliver cells under the physiological conditions they experience in vivo. One of the main characteristics of stem cells is their ability to self-renew to maintain a tissue for a lifetime. Stem cells’ unique characteristics are thought to be at least partially due to their location within enclosed protective microenvironments or niches. For corneal stem cells these are located in intricate microenvironments or niches situated within areas of the limbal region known as the Palisades of Vogt. These are located in the limbus which is the area between the cornea and sclera. In this study we introduced micropockets into biodegradable microfabricated membranes and explored the potential contribution of these structures to limbal cell migration and their ability to deliver cells to a 3D cornea model. Membranes with micropockets were characterized using SEM, OCT, light microscopy and nanoindentation. Results indicate that the micropockets enhance the migration of cells from limbal explants and cells transfer readily from the membranes to the ex vivo cornea model

Multiwavelength characterization of faint ultra steep spectrum radio sources: a search for high-redshift radio galaxies

Context. Ultra steep spectrum (USS) radio sources are one of the efficient tracers of powerful high-z radio galaxies (HzRGs). In contrast to searches for powerful HzRGs from radio surveys of moderate depths, fainter USS samples derived from deeper radio surveys can be useful in finding HzRGs at even higher redshifts and in unveiling a population of obscured weaker radio-loud AGN at moderate redshifts. Aims. Using our 325 MHz GMRT observations (5σ ∼ 800 μJy) and 1.4 GHz VLA observations (5σ ∼ 80−100 μJy) available in two subfields (VLA-VIMOS VLT Deep Survey (VLA-VVDS) and Subaru X-ray Deep Field (SXDF)) of the XMM-LSS field, we derive a large sample of 160 faint USS radio sources and characterize their nature. Methods. The optical and IR counterparts of our USS sample sources are searched using existing deep surveys, at respective wavelengths. We attempt to unveil the nature of our faint USS sources using diagnostic techniques based on mid-IR colors, flux ratios of radio to mid-IR, and radio luminosities. Results. Redshift estimates are available for 86/116 (∼74%) USS sources in the VLA-VVDS field and for 39/44 (∼87%) USS sources in the SXDF fields with median values (zmedian) ∼1.18 and ∼1.57, respectively, which are higher than estimates for non-USS radio sources (zmedian non−USS ∼ 0.99 and ∼0.96), in the two subfields. The MIR color–color diagnostic and radio luminosities are consistent with most of our USS sample sources at higher redshifts (z > 0.5) being AGN. The flux ratio of radio to mid-IR (S 1.4 GHz/S 3.6 μm) versus redshift diagnostic plot suggests that more than half of our USS sample sources distributed over z ∼ 0.5 to 3.8 are likely to be hosted in obscured environments. A significant fraction (∼26% in the VLA-VVDS and ∼13% in the SXDF) of our USS sources without redshift estimates mostly remain unidentified in the existing optical, IR surveys, and exhibit high radio to mid-IR flux ratio limits similar to HzRGs, and so, can be considered as potential HzRG candidates. Conclusions. Our study shows that the criterion of ultra steep spectral index remains a reasonably efficient method to select high-z sources even at sub-mJy flux densities. In addition to powerful HzRG candidates, our faint USS sample also contains populations of weaker radio-loud AGNs potentially hosted in obscured environments

Investigation of progressive damage and fracture in laminated composites using the smeared crack approach

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97056/1/AIAA2012-1537.pd

Pessaries (mechanical devices) for pelvic organ prolapse in women

BACKGROUND Pelvic organ prolapse is common, with some degree of prolapse seen in up to 50% of parous women in a clinic setting, although many are asymptomatic. The use of pessaries (a passive mechanical device designed to support the vagina) to treat prolapse is very common, and up to 77% of clinicians use pessaries for the first line management of prolapse. A number of symptoms may be associated with prolapse and treatments include surgery, pessaries and conservative therapies. A variety of pessaries are described which aim to alleviate the symptoms of prolapse and avert or delay the need for surgery. OBJECTIVES To determine the effectiveness of pessaries (mechanical devices) for pelvic organ prolapse. SEARCH METHODS We searched the Cochrane Incontinence Group Specialised Register of trials (searched 13 March 2012), which includes searches of CENTRAL, MEDLINE, PREMEDLINE and handsearching of conference proceedings, and handsearched the abstracts of two relevant conferences held in 2011. We also searched the reference lists of relevant articles. SELECTION CRITERIA Randomised and quasi-randomised controlled trials which included a pessary for pelvic organ prolapse in one arm of the study. DATA COLLECTION AND ANALYSIS Abstracts were assessed independently by two authors with arbitration from a third if necessary. Data extraction was completed independently for included studies by two review authors. MAIN RESULTS To date there is only one published randomised controlled trial assessing the use of pessaries in the treatment of pelvic organ prolapse. AUTHORS' CONCLUSIONS The review authors identified one randomised controlled trial comparing ring and Gellhorn pessaries. The results of the trial showed that both pessaries were effective for the approximately 60% of women who completed the study with no significant differences identified between the two types of pessary. However, methodological flaws were noted in the trial, as elaborated under risk of bias assessment. There is no consensus on the use of different types of device, the indications nor the pattern of replacement and follow-up care. There is an urgent need for randomised studies to address the use of pessaries in comparison with no treatment, surgery and conservative measures