The length-tension diagrams of human oblique muscles in trochlear palsy and strabismus sursoadductorius

We determined the relation between length and tension in detached oblique muscles of 16 strabismus patients that underwent surgery, before and during contraction evoked by intravenous administration of succinylcholine. We frequently found a nonlinear relation between length and tension, unlike our previous findings in recti. In superior oblique palsies, the superior oblique was found, before injection of succinylcholine, to be stiff after elongation, and did not contract after injection of succinylcholine, while the ipsilateral inferior oblique contract after injection of succinylcholine, but with a higher spring constant than did usual. In 3 cases the superior oblique contracted vividly after administration of succinylcholine despite the presence of excyclotropia, stereopsis, torticollis (2 cases) and a hypertropia that increased in adduction, in downgaze, in adduction-and-downgaze and on ipsilateral head-tilt. The finding of a vividly contracting superior oblique is incompatible with the diagnosis of a complete superior oblique palsy. We conclude that some of the cases diagnosed as congenital superior oblique palsy, having a hypertropia increasing in adduction, in downgaze, in adduction-and-downgaze and on ipsilateral head-tilt, are in fact cases of unilateral strabismus sursoadductorius (upshoot in adduction), a non-paretic motility disorder

Adolescents’ responses to the promotion and flavouring of e-cigarettes

Objectives The purpose of the study is to examine adolescents’ awareness of e-cigarette marketing and investigate the impact of e-cigarette flavour descriptors on perceptions of product harm and user image. Methods Data come from the 2014 Youth Tobacco Policy Survey, a cross-sectional in-home survey conducted with 11–16 year olds across the UK (n = 1205). Adolescents’ awareness of e-cigarette promotion, brands, and flavours was assessed. Perceptions of product harm, and likely user of four examples of e-cigarette flavours was also examined. Results Some participants had tried e-cigarettes (12 %) but regular use was low (2 %) and confined to adolescents who had also smoked tobacco. Most were aware of at least one promotional channel (82 %) and that e-cigarettes came in different flavours (69 %). Brand awareness was low. E-cigarettes were perceived as harmful (M = 3.54, SD = 1.19) but this was moderated by product flavours. Fruit and sweet flavours were perceived as more likely to be tried by young never smokers than adult smokers trying to quit (p < 0.001). Conclusions There is a need to monitor the impact of future market and regulatory change on youth uptake and perceptions of e-cigarettes

Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay. Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit. Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF

Gluonic and leptonic decays of heavy quarkonia and the determination of αs(mc)\alpha_s(m_c) and αs(mb)\alpha_s(m_b)

QCD running coupling constant $\alpha_s(m_c)$ and $\alpha_s(m_b)$ are determined from heavy quarkonia $c\overline{c}$ and $b\overline{b}$ decays. The decay rates of $V\rightarrow 3g$ and $V\rightarrow e^+ e^-$ for $V=J/\psi$ and $\Upsilon$ are estimated by taking into account both relativistic and QCD radiative corrections. The decay amplitudes are derived in the Bethe-Salpeter formalism, and the decay rates are estimated by using the meson wavefunctions which are obtained with a QCD-inspired inter-quark potential. For the $V\rightarrow 3g$ decay we find the relativistic correction to be very large and to severely suppress the decay rate. Using the experimental values of ratio R_g\equiv \frac {\Gamma (V\longrightarrow 3g)}% {\Gamma (V\longrightarrow e^{+}e^{-})}\approx 10,~32 for $V=J/\psi, ~\Upsilon$ respectively, and the calculated widths , we find $\alpha_{s}(m_c)=0.29\pm 0.02$ and $\alpha_s(m_b)=0.20\pm 0.02$. These values for the QCD running coupling constant are substantially enhanced, as compared with the ones obtained without relativistic corrections, and are consistent with the QCD scale parameter $\Lambda_{\overline {MS}}^{(4)}$. We also find that these results are mainly due to kinematic corrections and not sensitive to the dynamical models.Comment: 15 pages in Late

Pulmonary intravascular macrophages: Prime suspects as cellular mediators of porcine CARPA

Pigs provide a highly sensitive and quantitative in vivo model for complement (C) activation-related pseudoallergy (CARPA), a hypersensitivity reaction caused by some state-of-art nanomedicines. In an effort to understand the mechanism of the pigs' unique sensitivity for CARPA, this review focuses on pulmonary intravascular macrophages (PIMs), which are abundantly present in the lung of pigs. These cells represent a macrophage subpopulation whose unique qualities explain the characteristic symptoms of CARPA in this species, most importantly the rapidly (within minutes) developing pulmonary vasoconstriction, leading to elevation of pulmonary arterial pressure. The unique qualities of PIM cells include the following; 1) they are strongly adhered to the capillary walls via desmosome-like intercellular adhesion plaques, which secure stable and lasting direct exposition of the bulk of these cells to the blood stream; 2) their ruffled surface engaged in intense phagocytic activity ensures efficient binding and phagocytosis of nanoparticles; 3) PIM cells express anaphylatoxin receptors, this way C activation can trigger these cells, 4) they also express pattern recognition molecules on their surface, whose engagement with certain coated nanoparticles may also activate these cells or act in synergy with anaphylatoxins and, finally 5) their high metabolic activity and capability for immediate secretion of vasoactive mediators upon stimulation explain the circulatory blockage and other robust physiological effects that their stimulation may cause. These qualities taken together with reports on liposome uptake by PIM cells during CARPA and the possible presence of these cells in human lung suggests that PIM cells may be a potential therapeutic target against CARPA. © 2015 by De Gruyter

Coevolved mutations reveal distinct architectures for two core proteins in the bacterial flagellar motor

Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity.JK was supported by Medical Research Council grant U117581331. SK was supported by seed funds from Lahore University of Managment Sciences (LUMS) and the Molecular Biology Consortium

Cooperative Binding

Molecular binding is an interaction between molecules that results in a stable association between those molecules. Cooperative binding occurs if the number of binding sites of a macromolecule that are occupied by a specific type of ligand is a nonlinear function of this ligand’s concentration. This can be due, for instance, to an affinity for the ligand that depends on the amount of ligand bound. Cooperativity can be positive (supralinear) or negative (infralinear). Cooperative binding is most often observed in proteins, but nucleic acids can also exhibit cooperative binding, for instance of transcription factors. Cooperative binding has been shown to be the mechanism underlying a large range of biochemical and physiological processes

Association mapping of malting quality traits in UK spring and winter barley cultivar collections

Key Message: Historical malting quality data was collated from UK national and recommended list trial data and used in a GWAS. 25 QTL were identified, with the majority from spring barley cultivar sets. Abstract: In Europe, the most economically significant use of barley is the production of malt for use in the brewing and distilling industries. As such, selection for traits related to malting quality is of great commercial interest. In order to study the genetic basis of variation for malting quality traits in UK cultivars, a historical set of trial data was collated from national and recommended list trials from the period 1988 to 2016. This data was used to estimate variety means for 20 quality related traits in 451 spring barley cultivars, and 407 winter cultivars. Genotypes for these cultivars were generated using iSelect 9k and 50k genotyping platforms, and a genome wide association scan performed to identify malting quality quantitative trait loci (QTL). 24 QTL were identified in spring barley cultivars, and 2 from the winter set. A number of these correspond to known malting quality related genes but the remainder represents novel genetic variation that is accessible to breeders for the genetic improvement of new cultivars.Mark E. Looseley, Luke Ramsay, Hazel Bull, J. Stuart Swanston, Paul D. Shaw, Malcolm Macaulay, Allan Booth, Joanne R. Russell, Robbie Waugh, on behalf of the IMPROMALT Consortium, William T.B. Thoma