Multiple isoform recovery (MIR)-PCR: a simple method for the isolation of related mRNA isoforms

We present a rapid and efficient method for the detection of related transcripts with different expression levels. This approach combines the rapid amplification of cDNA ends (RACE) method with a cDNA subtractive technique. The strategy is based on successive subtractions of prevalent isoforms resulting in enrichment of less expressed transcripts. For each subtraction, a biotinylated primer specific for the prevalent isoform is hybridized on the total cDNA and the hybrid is retained on a streptavidin affinity column. The unbound cDNA serves as a template for subsequent isoform identification. To illustrate its application we describe the isolation of three new actin cDNA isoforms in the freshwater planarian Dugesia (S) polychro

Decompensated cirrhosis as presentation of LKM1/LC1 positive type 2 autoimmune hepatitis in adulthood. A rare clinical entity of difficult management

Background: Autoimmune hepatitis (AIH) is a chronic and aggressive liver disease that rapidly evolves into cirrhosis and end-stage liver disease if not timely diagnosed and treated with immunosuppressive therapy. AIH is classified into type 1 and type 2 according to the autoantibody pattern, with smooth muscle antibodies and/or antinuclear antibodies as serological markers of AIH-1, while antiliver cytosol antibody type 1 and/or antiliver/kidney microsomal antibody type 1 characterize type 2 AIH, which mainly affects children, including infants, and adolescents. Case Summary: We describe a case of type 2 AIH, clinically onset in a 34-year-old woman with decompensated cirrhosis. Only a thorough analysis of the autoantibody profile allowed for a diagnosis of an AIH-2 evolved into cirrhosis. The patient received a moderate corticosteroid therapy without achieving optimal disease control. We discuss the controversial decision of whether or not to treat the patient with immunosuppressive therapy, which should be balanced with the potential risk of infectious and other complications. A review of the literature on the management of patients with autoimmune cirrhosis is also presented. Conclusions: AIH-2 can be clinically onset in adult patients with cirrhosis and its complications, without being preceded by major clinical signs. Due to the difficult management of cirrhosis with immunosuppressive treatments, a patient-tailored strategy with a case-by-case approach is needed to prevent major complications such as infections, potentially precluding liver transplantation the only curative therapy

Cosmological zoo -- accelerating models with dark energy

ecent observations of type Ia supernovae indicate that the Universe is in an accelerating phase of expansion. The fundamental quest in theoretical cosmology is to identify the origin of this phenomenon. In principle there are two possibilities: 1) the presence of matter which violates the strong energy condition (a substantial form of dark energy), 2) modified Friedmann equations (Cardassian models -- a non-substantial form of dark matter). We classify all these models in terms of 2-dimensional dynamical systems of the Newtonian type. We search for generic properties of the models. It is achieved with the help of Peixoto's theorem for dynamical system on the Poincar{\'e} sphere. We find that the notion of structural stability can be useful to distinguish the generic cases of evolutional paths with acceleration. We find that, while the $\Lambda$CDM models and phantom models are typical accelerating models, the cosmological models with bouncing phase are non-generic in the space of all planar dynamical systems. We derive the universal shape of potential function which gives rise to presently accelerating models. Our results show explicitly the advantages of using a potential function (instead of the equation of state) to probe the origin of the present acceleration. We argue that simplicity and genericity are the best guide in understanding our Universe and its acceleration.Comment: RevTeX4, 23 pages, 10 figure

Meson-baryon components in the states of the baryon decuplet

We apply an extension of the Weinberg compositeness condition on partial waves of L = 1 and resonant states to determine the weight of the meson-baryon component in the Delta(1232) resonance and the other members of the baryon decuplet. We obtain an appreciable weight of pi N in the Delta(1232) wave function, of the order of 60%, which looks more natural when one recalls that experiments on deep inelastic and Drell Yan give a fraction of pi N component of 34% for the nucleon. We also show that, as we go to higher energies in the members of the decuplet, the weights of the meson-baryon component decrease and they already show a dominant part for a genuine, non-meson-baryon, component in the wave function. We write a section to interpret the meaning of the Weinberg sum rule when it is extended to complex energies and another one for the case of an energy-dependent potential

Dynamics and Variability of the Spring Dry Season in the United States Southwest as Observed in AmeriFlux and NLDAS-2 Data

The spring dry season occurring in an arid region of the southwestern United States, which receives both winter storm track and summer monsoon precipitation, is investigated. Bimodal precipitation and vegetation growth provide an opportunity to assess multiple climate mechanisms and their impact on hydroclimate and ecosystems. We detect multiple shifts from wet to drier conditions in the observational record and land surface model output. Focusing on the recent dry period, a shift in the late 1990s resulted in earlier and greater spring soil moisture draw down, and later and reduced spring vegetation green-up, compared to a prior wet period (1979–97). A simple soil moisture balance model shows this shift is driven by changes in winter precipitation. The recent post-1999 dry period and an earlier one from 1948 to 1966 are both related to the cool tropics phase of Pacific decadal variability, which influences winter precipitation. In agreement with other studies for the southwestern United States, we find the recent drought cannot be explained in terms of precipitation alone, but also is due to the rising influence of temperature, thus highlighting the sensitivity of this region to warming temperatures. Future changes in the spring dry season will therefore be affected by how tropical decadal variability evolves, and also by emerging trends due to human-driven warming

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

The Search for Gravitational Waves

Experiments aimed at searching for gravitational waves from astrophysical sources have been under development for the last 40 years, but only now are sensitivities reaching the level where there is a real possibility of detections being made within the next five years. In this article a history of detector development will be followed by a description of current detectors such as LIGO, VIRGO, GEO 600, TAMA 300, Nautilus and Auriga. Preliminary results from these detectors will be discussed and related to predicted detection rates for some types of sources. Experimental challenges for detector design are introduced and discussed in the context of detector developments for the future.Comment: 21 pages, 7 figures, accepted J. Phys. B: At. Mol. Opt. Phy

Developing the specifications of an Open Angle Glaucoma screening intervention in the United Kingdom : a Delphi approach

PMID: 23216983 [PubMed - indexed for MEDLINE] PMCID: PMC3563574 Free PMC Article Acknowledgements We thank all the glaucoma specialists who took part in the Delphi process. We thank the Glaucoma screening Platform Study advisory panel including R Bativala, D Crabb, D Garway-Heath, M Griffiths, R Hitchings; S McPherson, A Tuulonen, A Viswanathan, H Waterman, R Wormald, D Wright for their guidance and contribution to the Delphi process and Luke Vale and Rodolfo Hernandez for their advice on development of the Delphi questionnaires. This paper was developed from the first phase of a project funded by the MRC (project reference G0701759) Developing the intervention & outcome components of a proposed randomized controlled trial of screening for open angle glaucoma. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health Directorates. The views expressed in this report are those of the authors and not necessarily those of the funders.Peer reviewedPublisher PD

A proposal for multi-tens of GW fully coherent femtosecond soft X-ray lasers

X-ray free-electron lasers1,2 delivering up to 131013 coherent photons in femtosecond pulses are bringing about a revolution in X-ray science3?5. However, some plasma-based soft X-ray lasers6 are attractive because they spontaneously emit an even higher number of photons (131015), but these are emitted in incoherent and long (hundreds of picoseconds) pulses7 as a consequence of the amplification of stochastic incoherent self-emission. Previous experimental attempts to seed such amplifiers with coherent femtosecond soft X-rays resulted in as yet unexplained weak amplification of the seed and strong amplification of incoherent spontaneous emission8. Using a time-dependent Maxwell?Bloch model describing the amplification of both coherent and incoherent soft X-rays in plasma, we explain the observed inefficiency and propose a new amplification scheme based on the seeding of stretched high harmonics using a transposition of chirped pulse amplification to soft X-rays. This scheme is able to deliver 531014 fully coherent soft X-ray photons in 200 fs pulses and with a peak power of 20 GW

Measures of socioeconomic status and self-reported glaucoma in the UK Biobank cohort

Purpose: To determine ocular, demographic, and socioeconomic associations with self-reported glaucoma in the UK Biobank.Methods: Biobank is a study of UK residents aged 40–69 years registered with the National Health Service. Data were collected on visual acuity, intraocular pressure (IOP), corneal biomechanics, and questionnaire from 112?690 participants. Relationships between ocular, demographic, and socioeconomic variables with reported diagnosis of glaucoma were examined.Results: In all, 1916 (1.7%) people in UK Biobank reported glaucoma diagnosis. Participants reporting glaucoma were more likely to be older (mean 61.4 vs 56.7 years, P&lt;0.001) and male (2.1% vs 1.4%, P=0.001). The rate of reported glaucoma was significantly higher in Black (3.28%, P&lt;0.001) and Asian (2.14%, P=0.009) participants compared with White participants (1.62%, reference). Cases of reported glaucoma had a higher mean IOP (18?mm?Hg both eyes, P&lt;0.001), lower corneal hysteresis (9.96 right eye, 9.89 left eye, P&lt;0.001), and lower visual acuity (0.09 logMAR right eye, 0.08 logMAR left eye, P&lt;0.001) compared with those without (16?mm?Hg both eyes, hysteresis 10.67 right eye, 10.63 left eye, 0.03 logMAR right eye, 0.02 logMAR left eye). The mean Townsend deprivation index was ?0.72 for those reporting glaucoma and ?0.95 for those without (P&lt;0.001), indicating greater relative deprivation in those reporting glaucoma. Multivariable logistic regression showed that people in the lowest income group (&lt;£18?000/year) were significantly more likely to report a diagnosis of glaucoma compared with any other income level (P&lt;0.01). We observed increasing glaucoma risk across the full range of income categories, with highest risk among those of lowest income, and no evidence of a threshold effect.Conclusions: In a large UK cohort, individuals reporting glaucoma had more adverse socioeconomic characteristics. Study of the mechanisms explaining these effects may aid our understanding of health inequality and will help inform public health interventions