304 research outputs found
Non-commutative flux representation for loop quantum gravity
The Hilbert space of loop quantum gravity is usually described in terms of
cylindrical functionals of the gauge connection, the electric fluxes acting as
non-commuting derivation operators. It has long been believed that this
non-commutativity prevents a dual flux (or triad) representation of loop
quantum gravity to exist. We show here, instead, that such a representation can
be explicitly defined, by means of a non-commutative Fourier transform defined
on the loop gravity state space. In this dual representation, flux operators
act by *-multiplication and holonomy operators act by translation. We describe
the gauge invariant dual states and discuss their geometrical meaning. Finally,
we apply the construction to the simpler case of a U(1) gauge group and compare
the resulting flux representation with the triad representation used in loop
quantum cosmology.Comment: 12 pages, matches published versio
Increased levels of RNA oxidation enhance the reversion frequency in aging pro-apoptotic yeast mutants
Despite recent advances in understanding the complexity of RNA processes, regulation of the metabolism of oxidized cellular RNAs and the mechanisms through which oxidized ribonucleotides affect mRNA translation, and consequently cell viability, are not well characterized. We show here that the level of oxidized RNAs is markedly increased in a yeast decapping Kllsm4Δ1 mutant, which accumulates mRNAs, ages much faster that the wild type strain and undergoes regulated-cell-death. We also found that in Kllsm4Δ1 cells the mutation rate increases during chronological life span indicating that the capacity to han- dle oxidized RNAs in yeast declines with aging. Lowering intracellular ROS levels by antioxidants recovers the wild- type phenotype of mutant cells, including reduced amount of oxidized RNAs and lower mutation rate. Since mRNA oxidation was reported to occur in different neurodegen- erative diseases, decapping-deficient cells may represent a useful tool for deciphering molecular mechanisms of cell response to such conditions, providing new insights into RNA modification-based pathogenesis
A left circumflex aorta with a displaced thoracic duct in a 94-year-old male cadaver: a case report with discussion on embryology
A left circumflex aorta (LCA) is an extremely rare variation of the thoracic aorta. It is distinguished by a retroesophageal descending aorta that subsequently travels down the right side of the thoracic vertebrae towards the aortic hiatus. Nonetheless, its embryological origin ought not to be overly generalized, but each case should be considered individually due to its unique vascular patterns. This study presents a description of a LCA in a 94-year-old male cadaver. The dissection revealed the descending aorta posteriorly from the trachea and esophagus and then laterally on the right from the thoracic vertebral bodies. The branching pattern of the aortic arch was typical, so was the course of the left and right recurrent laryngeal nerves. However, the thoracic duct was placed on the right, and drained into the right internal carotid vein. Due to the normal appearance of the ascending part and the arch of the aorta, it is safe to presume that the variation originated from the persistent right dorsal aorta, with the retroesophageal part from the persistent left dorsal aorta. Detailed understanding of the variations of the thoracic aorta, and the anomalies associated with the LCA, can help to improve management of these conditions, and with that, improve patients’ overall outcomes. Patients with a LCA, or another vascular ring, can either be asymptomatic or present with esophageal and / or tracheal compression symptoms. Management of this anomaly consists namely of ligation of the patent ductus arteriosus / ligamentum arteriosum and aortic uncrossing
Background Independent Quantum Gravity: A Status Report
The goal of this article is to present an introduction to loop quantum
gravity -a background independent, non-perturbative approach to the problem of
unification of general relativity and quantum physics, based on a quantum
theory of geometry. Our presentation is pedagogical. Thus, in addition to
providing a bird's eye view of the present status of the subject, the article
should also serve as a vehicle to enter the field and explore it in detail. To
aid non-experts, very little is assumed beyond elements of general relativity,
gauge theories and quantum field theory. While the article is essentially
self-contained, the emphasis is on communicating the underlying ideas and the
significance of results rather than on presenting systematic derivations and
detailed proofs. (These can be found in the listed references.) The subject can
be approached in different ways. We have chosen one which is deeply rooted in
well established physics and also has sufficient mathematical precision to
ensure that there are no hidden infinities. In order to keep the article to a
reasonable size, and to avoid overwhelming non-experts, we have had to leave
out several interesting topics, results and viewpoints; this is meant to be an
introduction to the subject rather than an exhaustive review of it.Comment: 125 pages, 5 figures (eps format), the final version published in CQ
Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores
The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization
Involvement of yeast HSP90 isoforms in response to stress and cell death induced by acetic acid
Acetic acid-induced apoptosis in yeast is accompanied by an impairment of the general protein synthesis machinery, yet paradoxically also by the up-regulation of the two isoforms of the heat shock protein 90 (HSP90) chaperone family, Hsc82p and Hsp82p. Herein, we show that impairment of cap-dependent translation initiation induced by acetic acid is caused by the phosphorylation and inactivation of eIF2 alpha by Gcn2p kinase. A microarray analysis of polysome-associated mRNAs engaged in translation in acetic acid challenged cells further revealed that HSP90 mRNAs are over-represented in this polysome fraction suggesting preferential translation of HSP90 upon acetic acid treatment. The relevance of HSP90 isoform translation during programmed cell death (PCD) was unveiled using genetic and pharmacological abrogation of HSP90, which suggests opposing roles for HSP90 isoforms in cell survival and death. Hsc82p appears to promote survival and its deletion leads to necrotic cell death, while Hsp82p is a pro-death molecule involved in acetic acid-induced apoptosis. Therefore, HSP90 isoforms have distinct roles in the control of cell fate during PCD and their selective translation regulates cellular response to acetic acid stress.This work was supported by Fundacao para a Ciencia e Tecnologia and COMPETE/QREN/EU (PTDC/BIA-MIC/114116/2009), and by the Canadian Institute for Health Research (MOP 89737 to MH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Retinal vessel diameters and reactivity in diabetes mellitus and/or cardiovascular disease
Background: Retinal vessel calibre and vascular dilation/constriction in response to flicker light provocation may provide a measure distinguishing patients suffering from diabetes mellitus and/or cardiovascular disease. Methods: One hundred and sixteen age and sex matched patients with diabetes mellitus (DM), cardiovascular disease (CVD) and both DM and CVD (DM+CVD) underwent systemic and intraocular pressure measurements. Retinal vessel calibres were assessed using a validated computer-based program to compute central retinal artery and vein equivalents (CRVE) from monochromatic retinal images. Vessel dilation and constriction responses to flicker light provocation were assessed by continuous retinal vessel diameter recordings. Plasma endothelial markers von Willebrand factor (vWf) and soluble E selectin (sEsel) were measured by ELISA. Results: Retinal vessel calibres were comparable across groups but CRVE correlated significantly with disease duration in DM patients (r=0.57, p<0.001). Patients suffering DM only exhibited reduced arterial vasomotion at rest and reduced arterial constriction following flicker light induced vessel dilation compared to patients with CVD and those suffering both CVD+DM (p=0.030). Patients suffering from CVD+DM exhibited significant differences between each flicker cycle in regards to arterial maximum constriction (p=0.006) and time needed to reach arterial maximum dilation (p=0.004), whereas the other two groups did not show such inconsistencies between individual flicker cycles. vWf was raised in CVD+DM compared to the other two groups (p≤0.02), whilst sEsel was raised in CVD+DM compared to DM alone (p=0.044). Conclusions: Dynamic retinal vascular calibres as obtained by continuous diameter measurements using flicker light provocation can reveal subtle differences between groups suffering from CVD with and without DM. This difference in reaction pattern and lack of arterial constriction in DM may provide a suitable marker to monitor progression
Diversity of Pol IV Function Is Defined by Mutations at the Maize rmr7 Locus
Mutations affecting the heritable maintenance of epigenetic states in maize identify multiple small RNA biogenesis factors including NRPD1, the largest subunit of the presumed maize Pol IV holoenzyme. Here we show that mutations defining the required to maintain repression7 locus identify a second RNA polymerase subunit related to Arabidopsis NRPD2a, the sole second largest subunit shared between Arabidopsis Pol IV and Pol V. A phylogenetic analysis shows that, in contrast to representative eudicots, grasses have retained duplicate loci capable of producing functional NRPD2-like proteins, which is indicative of increased RNA polymerase diversity in grasses relative to eudicots. Together with comparisons of rmr7 mutant plant phenotypes and their effects on the maintenance of epigenetic states with parallel analyses of NRPD1 defects, our results imply that maize utilizes multiple functional NRPD2-like proteins. Despite the observation that RMR7/NRPD2, like NRPD1, is required for the accumulation of most siRNAs, our data indicate that different Pol IV isoforms play distinct roles in the maintenance of meiotically-heritable epigenetic information in the grasses
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