Mutation of Arabidopsis SPLICEOSOMAL TIMEKEEPER LOCUS1 Causes Circadian Clock Defects

The circadian clock plays a crucial role in coordinating plant metabolic and physiological functions with predictable environmental variables, such as dusk and dawn, while also modulating responses to biotic and abiotic challenges. Much of the initial characterization of the circadian system has focused on transcriptional initiation, but it is now apparent that considerable regulation is exerted after this key regulatory step. Transcript processing, protein stability, and cofactor availability have all been reported to influence circadian rhythms in a variety of species. We used a genetic screen to identify a mutation within a putative RNA binding protein (SPLICEOSOMAL TIMEKEEPER LOCUS1 [STIPL1]) that induces a long circadian period phenotype under constant conditions. STIPL1 is a homolog of the spliceosomal proteins TFP11 (Homo sapiens) and Ntr1p (Saccharomyces cerevisiae) involved in spliceosome disassembly. Analysis of general and alternative splicing using a high-resolution RT-PCR system revealed that mutation of this protein causes less efficient splicing of most but not all of the introns analyzed. In particular, the altered accumulation of circadian-associated transcripts may contribute to the observed mutant phenotype. Interestingly, mutation of a close homolog of STIPL1, STIP-LIKE2, does not cause a circadian phenotype, which suggests divergence in function between these family members. Our work highlights the importance of posttranscriptional control within the clock mechanism. © 2012 American Society of Plant Biologists. All rights reserved

Australian SMEs: Waste sent to landfill

Landfill waste has a negative impact on the environment and Small and Medium Enterprises (SMEs) are believed to be significant contributors. There is little government or scholarly research, however, quantifying the collective volume of waste SMEs send to landfill. The limited studies instead measure total volumes (landfill and recycling combined) and/or do not distinguish between specific waste streams (e.g. wood) and subcategories (e.g. dust). This paper contributes to knowledge by reconceptualising SME waste into subcategories and by measuring landfill volumes. It presents findings from 404 Australian SMEs which found that, in descending order, cardboard, paper, plastic wrap, wood dust and particleboard were the subcategories these SMEs sent to landfill in the greatest volumes. It also argues that this reconceptualisation and associated data collection protocols have the potential to enable scholars and policymakers to determine the waste subcategories to which SMEs contribute most, formulate targeted interventions and research/evaluate environmental outcomes

Prosthesis use is associated with reduced physical self-disgust in limb amputees

Self-disgust is an emotion schema negatively affecting people’s body image and is triggered by bodily imperfections and deviations from the “normal” body envelope. In this study, we explore the idea that “normalising” the body in those with limb amputations via the prosthesis would be linked to reduced self-directed disgust. An international clinical community sample (N = 83) with mostly lower limb amputations completed measures about their demographics, prosthesis, adjustment, body image disturbance, psychological distress, and self-directed disgust in a survey design. Consistent with the “normalising” hypothesis, correlation and bootstrapped regression models revealed, first, that frequency of prosthesis use was significantly and negatively associated with physical self-disgust. Second, prosthesis use significantly mediated the exogenous effect of time since amputation on physical self-disgust. These results emphasise the psychological value of the prosthesis beyond its functional use, and stress its importance in normalising the body envelope in those with limb amputations, which may in turn promote psychological well-being

No impact of CMV or EBV seropositivity on the frequency of highly differentiated T-cells in Mexican-American adolescents

Recurring activations of the prevalent latent herpes viruses Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) induces immune cell division leading to the premature terminal differentiation of T-cells. Terminally differentiated T-cells are known to accumulate with age causing a reduction in the naïve T-cell repertoire, which compromises the ability of the adaptive immune system to respond to novel pathogens. Although CMV and EBV seropositivity are hallmarks of the “immune risk profile” and are known to influence the frequency of terminally differentiated T-cells and increase infection risk in adults, it is not known if CMV or EBV impacts on the frequency of these cells in a young subject cohort. PURPOSE: To examine the impact of CMV and EBV seropositivity on the frequency of highly differentiated blood T-cells in Mexican-American adolescents. METHODS: Fasted resting blood samples were obtained from 77 adolescents consisting of both males and females. The presence of antibodies against CMV and EBV was determined in serum by ELISA. Lymphocytes isolated from peripheral blood were assessed for a combination of cell surface markers to determine their stage of differentiation. Monoclonal antibodies and four-color flow cytometry were used to identify senescent (CD27-, CD28-, CD57+), naïve (CCR7+, CD45RA+), memory (CCR7-, CD45RA-) and effector memory (CCD7-, CD45RA+) T-cell markers on pan CD3+ T-cells, CD4+ T-cells and CD8+ T-cells. Differences in T-cell phenotype between the CMV/EBV seropositive and seronegative participants were compared using independent Student t-tests. RESULTS: The prevalence of latent CMV and EBV infection among the subject cohort was 16% and 44% respectively, while 7% of all participants were carrying a latent infection for both. No differences in senescent and memory phenotypes were found between the CMV or EBV seropositive and seronegative groups. CONCLUSION: Despite the known influence of latent CMV and EBV infection on the frequency of senescent T-cells in adults, these preliminary data indicate that CMV and EBV seropositivity has no impact on the frequency of senescent T-cells in adolescents. These data suggest that the increased frequency of terminally differentiated T-cells that are associated with CMV and EBV seropositivity in adults is probably due to long-term infections. Future studies will assess the impact of CMV and EBV seropositivity on immunosenescence in association with other factors known to have an effect on T-cells differentiation, such as BMI and physical activity status

Ill-posedness of degenerate dispersive equations

In this article we provide numerical and analytical evidence that some degenerate dispersive partial differential equations are ill-posed. Specifically we study the K(2,2) equation $u_t = (u^2)_{xxx} + (u^2)_{x}$ and the "degenerate Airy" equation $u_t = 2 u u_{xxx}$. For K(2,2) our results are computational in nature: we conduct a series of numerical simulations which demonstrate that data which is very small in $H^2$ can be of unit size at a fixed time which is independent of the data's size. For the degenerate Airy equation, our results are fully rigorous: we prove the existence of a compactly supported self-similar solution which, when combined with certain scaling invariances, implies ill-posedness (also in $H^2$)

Human gene copy number spectra analysis in congenital heart malformations

The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 groups and verified in accordance with the European Paediatric Cardiac Code, were compared with two control groups, a disease-free cohort (n = 2,026) and a population with coronary artery disease (n = 880). Gains (≥200 kb) and losses (≥100 kb) were determined over 100 CHD risk genes and compared using a Barnard exact test. Six subphenotypes showed significant enrichment (P ≤ 0.05), including aortic stenosis (valvar), atrioventricular canal (partial), atrioventricular septal defect with tetralogy of Fallot, subaortic stenosis, tetralogy of Fallot, and truncus arteriosus. Furthermore, CNV gene frequency spectra were enriched (P ≤ 0.05) for losses at: FKBP6, ELN, GTF2IRD1, GATA4, CRKL, TBX1, ATRX, GPC3, BCOR, ZIC3, FLNA and MID1; and gains at: PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, HRAS, GATA6 and RUNX1. Of CHD subjects, 14% had causal chromosomal abnormalities, and 4.3% had likely causal (significantly enriched), large, rare CNVs. CNV frequency spectra combined with precision phenotyping may lead to increased molecular understanding of etiologic pathways

Synthesis and magnetic properties of a copper cube : [Cu4(OH)4(C16H18N2)4]4+ (ClO4)4 C3H6O [C16H18N2 = (E)-1,6-[di(pyridin-4-yl)hex-3-ene

We are grateful to the National Mass Spectrometry Service Center for mass spectra and to the UK National Crystallography Service for data sets. Supplementary Figure S1-S4: IR and UV/Vis spectra of compound 1Peer reviewedPublisher PD

Quantification of atopy, lung function and airway hypersensitivity in adults

<p>Abstract</p> <p>Background</p> <p>Studies in children have shown that concentration of specific serum IgE (sIgE) and size of skin tests to inhalant allergens better predict wheezing and reduced lung function than the information on presence or absence of atopy. However, very few studies in adults have investigated the relationship of quantitative atopy with lung function and airway hyperresponsiveness (AHR).</p> <p>Objective</p> <p>To determine the association between lung function and AHR and quantitative atopy in a large sample of adults from the UK.</p> <p>Methods</p> <p>FEV₁ and FVC (% predicted) were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma). Atopic status was assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant allergens). We also measured indoor allergen exposure in subjects' homes.</p> <p>Results</p> <p>Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV₁ (mite p = 0.001, cat p = 0.0001, dog p = 2.95 × 10^-8). Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 × 10^-8, cat p = 3.93 × 10^-10, dog p = 3.03 × 10^-15, grass p = 2.95 × 10^-9). The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control).</p> <p>Conclusions</p> <p>In the studied population, lung function decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to inhalant allergens, suggesting that atopy may not be a dichotomous outcome influencing lung function and AHR.</p

The Impact of Sensitive Research on the Researcher: Preparedness and Positionality

There is currently limited research exploring the impact of undertaking sensitive or challenging research on the researcher, although some textbooks explore researcher preparedness. This article presents a discussion of the findings from a research project which engaged with the seldom heard voices of researchers themselves. The aim was to explore researchers’ experiences of undertaking research on sensitive topics, or with marginalized groups, as this can expose researchers to emotionally disturbing situations throughout data collection and analysis, which can be psychologically challenging. Although ethical codes of practice include discussion around protection of both the researcher and the participant, in practice, the ethics approval process rarely considers the impact of the proposed research on the researcher. Their experiences are therefore seldom acknowledged or heard, resulting in potential distress for the researcher. Semistructured interviews were undertaken with social science researchers from a range of discipline backgrounds and at different points in their research careers (n = 10). This article explores two themes emerging from the data: preparedness and positionality. It considers what these themes mean in terms of supporting researchers who encounter challenging research data, and issues related to supporting researcher reflexivity and the requirements for institutional support offered to researchers will also be considered

Non-Invasive Prenatal Detection of Trisomy 21 Using Tandem Single Nucleotide Polymorphisms

BACKGROUND: Screening tests for Trisomy 21 (T21), also known as Down syndrome, are routinely performed for the majority of pregnant women. However, current tests rely on either evaluating non-specific markers, which lead to false negative and false positive results, or on invasive tests, which while highly accurate, are expensive and carry a risk of fetal loss. We outline a novel, rapid, highly sensitive, and targeted approach to non-invasively detect fetal T21 using maternal plasma DNA. METHODS AND FINDINGS: Highly heterozygous tandem Single Nucleotide Polymorphism (SNP) sequences on chromosome 21 were analyzed using High-Fidelity PCR and Cycling Temperature Capillary Electrophoresis (CTCE). This approach was used to blindly analyze plasma DNA obtained from peripheral blood from 40 high risk pregnant women, in adherence to a Medical College of Wisconsin Institutional Review Board approved protocol. Tandem SNP sequences were informative when the mother was heterozygous and a third paternal haplotype was present, permitting a quantitative comparison between the maternally inherited haplotype and the paternally inherited haplotype to infer fetal chromosomal dosage by calculating a Haplotype Ratio (HR). 27 subjects were assessable; 13 subjects were not informative due to either low DNA yield or were not informative at the tandem SNP sequences examined. All results were confirmed by a procedure (amniocentesis/CVS) or at postnatal follow-up. Twenty subjects were identified as carrying a disomy 21 fetus (with two copies of chromosome 21) and seven subjects were identified as carrying a T21 fetus. The sensitivity and the specificity of the assay was 100% when HR values lying between 3/5 and 5/3 were used as a threshold for normal subjects. CONCLUSIONS: In summary, a targeted approach, based on calculation of Haplotype Ratios from tandem SNP sequences combined with a sensitive and quantitative DNA measurement technology can be used to accurately detect fetal T21 in maternal plasma when sufficient fetal DNA is present in maternal plasma