Large spin systematics in CFT

20 pages; v2: version published in JHEPUsing conformal field theory (CFT) arguments we derive an infinite number of constraints on the large spin expansion of the anomalous dimensions and structure constants of higher spin operators. These arguments rely only on analiticity, unitarity, crossing-symmetry and the structure of the conformal partial wave expansion. We obtain results for both, perturbative CFT to all order in the perturbation parameter, as well as non-perturbatively. For the case of conformal gauge theories this provides a proof of the reciprocity principle to all orders in perturbation theory and provides a new "reciprocity" principle for structure constants. We argue that these results extend also to non-conformal theories.Peer reviewe

Interaction between row-type genes in barley controls meristem determinacy and reveals novel routes to improved grain

Hordeum species develop a central spikelet flanked by two lateral spikelets at each inflorescence node. In 'two-rowed' spikes, the central spikelet alone is fertile and sets grain, while in 'six-rowed' spikes, lateral spikelets can also produce grain. Induced loss-of-function alleles of any of five Six-rowed spike (VRS) genes (VRS1-5) cause complete to intermediate gains of lateral spikelet fertility. Current six-row cultivars contain natural defective vrs1 and vrs5 alleles. Little information is known about VRS mechanism(s). We used comparative developmental, expression and genetic analyses on single and double vrs mutants to learn more about how VRS genes control development and assess their agronomic potential. We show that all VRS genes repress fertility at carpel and awn emergence in developing lateral spikelets. VRS4, VRS3 and VRS5 work through VRS1 to suppress fertility, probably by inducing VRS1 expression. Pairing vrs3, vrs4 or vrs5 alleles increased lateral spikelet fertility, despite the presence of a functional VRS1 allele. The vrs3 allele caused loss of spikelet identity and determinacy, improved grain homogeneity and increased tillering in a vrs4 background, while with vrs5, decreased tiller number and increased grain weight. Interactions amongst VRS genes control spikelet infertility, determinacy and outgrowth, and novel routes to improving six-row grain.Monika Zwirek, Robbie Waugh, Sarah M. McKi

Zinc and zinc transporters in macrophages and their roles in efferocytosis in COPD

Our previous studies have shown that nutritional zinc restriction exacerbates airway inflammation accompanied by an increase in caspase-3 activation and an accumulation of apoptotic epithelial cells in the bronchioles of the mice. Normally, apoptotic cells are rapidly cleared by macrophage efferocytosis, limiting any secondary necrosis and inflammation. We therefore hypothesized that zinc deficiency is not only pro-apoptotic but also impairs macrophage efferocytosis. Impaired efferocytic clearance of apoptotic epithelial cells by alveolar macrophages occurs in chronic obstructive pulmonary disease (COPD), cigarette-smoking and other lung inflammatory diseases. We now show that zinc is a factor in impaired macrophage efferocytosis in COPD. Concentrations of zinc were significantly reduced in the supernatant of bronchoalveolar lavage fluid of patients with COPD who were current smokers, compared to healthy controls, smokers or COPD patients not actively smoking. Lavage zinc was positively correlated with AM efferocytosis and there was decreased efferocytosis in macrophages depleted of Zn in vitro by treatment with the membrane-permeable zinc chelator TPEN. Organ and cell Zn homeostasis are mediated by two families of membrane ZIP and ZnT proteins. Macrophages of mice null for ZIP1 had significantly lower intracellular zinc and efferocytosis capability, suggesting ZIP1 may play an important role. We investigated further using the human THP-1 derived macrophage cell line, with and without zinc chelation by TPEN to mimic zinc deficiency. There was no change in ZIP1 mRNA levels by TPEN but a significant 3-fold increase in expression of another influx transporter ZIP2, consistent with a role for ZIP2 in maintaining macrophage Zn levels. Both ZIP1 and ZIP2 proteins were localized to the plasma membrane and cytoplasm in normal human lung alveolar macrophages. We propose that zinc homeostasis in macrophages involves the coordinated action of ZIP1 and ZIP2 transporters responding differently to zinc deficiency signals and that these play important roles in macrophage efferocytosis

The kinases MSK1 and MSK2 act as negative regulators of Toll-like receptor signaling

The kinases MSK1 and MSK2 are activated 'downstream' of the p38 and Erk1/2 mitogen-activated protein kinases. Here we found that MSK1 and MSK2 were needed to limit the production of proinflammatory cytokines in response to stimulation of primary macrophages with lipopolysaccharide. By inducing transcription of the mitogen-activated protein kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10, MSK1 and MSK2 exerted many negative feedback mechanisms. Deficiency in MSK1 and MSK2 prevented the binding of phosphorylated transcription factors CREB and ATF1 to the promoters of the genes encoding interleukin 10 and DUSP1. Mice doubly deficient in MSK1 and MSK2 were hypersensitive to lipopolysaccharide-induced endotoxic shock and showed prolonged inflammation in a model of toxic contact eczema induced by phorbol 12-myristate 13-acetate. Our results establish MSK1 and MSK2 as key components of negative feedback mechanisms needed to limit Toll-like receptor-driven inflammation.</p

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

Left ventricular non-compaction: clinical features and cardiovascular magnetic resonance imaging

Background: It is apparent that despite lack of family history, patients with the morphological characteristics of left ventricular non-compaction develop arrhythmias, thrombo-embolism and left ventricular dysfunction. METHODS: Forty two patients, aged 48.7 +/- 2.3 yrs (mean +/- SEM) underwent cardiovascular magnetic resonance (CMR) for the quantification of left ventricular volumes and extent of non-compacted (NC) myocardium. The latter was quantified using planimetry on the two-chamber long axis LV view (NC area). The patients included those referred specifically for CMR to investigate suspected cardiomyopathy, and as such is represents a selected group of patients. RESULTS: At presentation, 50% had dyspnoea, 19% chest pain, 14% palpitations and 5% stroke. Pulmonary embolism had occurred in 7% and brachial artery embolism in 2%. The ECG was abnormal in 81% and atrial fibrillation occurred in 29%. Transthoracic echocardiograms showed features of NC in only 10%. On CMR, patients who presented with dyspnoea had greater left ventricular volumes (both p < 0.0001) and a lower left ventricular ejection fraction (LVEF) (p < 0.0001) than age-matched, healthy controls. In patients without dyspnoea (n = 21), NC area correlated positively with end-diastolic volume (r = 0.52, p = 0.0184) and end-systolic volume (r = 0.56, p = 0.0095), and negatively with EF (r = -0.72, p = 0.0001). CONCLUSION: Left ventricular non-compaction is associated with dysrrhythmias, thromboembolic events, chest pain and LV dysfunction. The inverse correlation between NC area and EF suggests that NC contributes to left ventricular dysfunction

Disability discrimination and well-being in the United Kingdom: a prospective cohort study

Objectives: Disability discrimination is linked with poorer well-being cross-sectionally. The aim of this study was to explore prospective associations between disability discrimination and well-being. / Design: Prospective cohort study. / Setting: The United Kingdom Household Longitudinal Study. / Participants: Data were from 871 individuals with a self-reported physical, cognitive or sensory disability. / Primary outcome measures: Depression was assessed in 2009/10. Psychological distress, mental functioning, life satisfaction and self-rated health were assessed in 2009/10 and 2013/14. / Results: Data were analysed using linear and logistic regression with adjustment for age, sex, household income, education, ethnicity and impairment category. Perceived disability discrimination was reported by 117 (13.4%) participants. Cross-sectionally, discrimination was associated with depression (OR=5.40, 95% CI 3.25 to 8.97) fair/poor self-rated health (OR=2.05; 95% CI 1.19 to 3.51), greater psychological distress (B=3.28, 95% CI 2.41 to 4.14), poorer mental functioning (B=−7.35; 95% CI −9.70 to −5.02) and life satisfaction (B=−1.27, 95% CI −1.66 to −0.87). Prospectively, discrimination was associated with increased psychological distress (B=2.88, 95% CI 1.39 to 4.36) and poorer mental functioning (B=−5.12; 95% CI −8.91 to −1.34), adjusting for baseline scores. / Conclusions: Perceived disability-related discrimination is linked with poorer well-being. These findings underscore the need for interventions to combat disability discrimination

Recent Advances in Graph Partitioning

We survey recent trends in practical algorithms for balanced graph partitioning together with applications and future research directions