Pulmonary ORMDL3 is critical for induction of Alternaria -induced allergic airways disease

Genome-wide association studies have identified the ORM (yeast)-like protein isoform 3 (ORMDL3) gene locus on human chromosome 17q to be a highly significant risk factor for childhood-onset asthma. Objective We sought to investigate in vivo the functional role of ORMDL3 in disease inception. Methods An Ormdl3-deficient mouse was generated and the role of ORMDL3 in the generation of allergic airways disease to the fungal aeroallergen Alternaria alternata was determined. An adeno-associated viral vector was also used to reconstitute ORMDL3 expression in airway epithelial cells of Ormdl3 knockout mice. Results Ormdl3 knockout mice were found to be protected from developing allergic airways disease and showed a marked decrease in pathophysiology, including lung function and airway eosinophilia induced by Alternaria. Alternaria is a potent inducer of cellular stress and the unfolded protein response, and ORMDL3 was found to play a critical role in driving the activating transcription factor 6–mediated arm of this response through Xbp1 and downstream activation of the endoplasmic reticulum–associated degradation pathway. In addition, ORMDL3 mediated uric acid release, another marker of cellular stress. In the knockout mice, reconstitution of Ormdl3 transcript levels specifically in the bronchial epithelium resulted in reinstatement of susceptibility to fungal allergen–induced allergic airways disease. Conclusions This study demonstrates that ORMDL3, an asthma susceptibility gene identified by genome-wide association studies, contributes to key pathways that promote changes in airway physiology during allergic immune responses

Simultaneous Orthogonal Planarity

We introduce and study the $\textit{OrthoSEFE}-k$ problem: Given $k$ planar graphs each with maximum degree 4 and the same vertex set, do they admit an OrthoSEFE, that is, is there an assignment of the vertices to grid points and of the edges to paths on the grid such that the same edges in distinct graphs are assigned the same path and such that the assignment induces a planar orthogonal drawing of each of the $k$ graphs? We show that the problem is NP-complete for $k \geq 3$ even if the shared graph is a Hamiltonian cycle and has sunflower intersection and for $k \geq 2$ even if the shared graph consists of a cycle and of isolated vertices. Whereas the problem is polynomial-time solvable for $k=2$ when the union graph has maximum degree five and the shared graph is biconnected. Further, when the shared graph is biconnected and has sunflower intersection, we show that every positive instance has an OrthoSEFE with at most three bends per edge.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

Orientation cues for high-flying nocturnal insect migrants: do turbulence-induced temperature and velocity fluctuations indicate the mean wind flow?

Migratory insects flying at high altitude at night often show a degree of common alignment, sometimes with quite small angular dispersions around the mean. The observed orientation directions are often close to the downwind direction and this would seemingly be adaptive in that large insects could add their self-propelled speed to the wind speed, thus maximising their displacement in a given time. There are increasing indications that high-altitude orientation may be maintained by some intrinsic property of the wind rather than by visual perception of relative ground movement. Therefore, we first examined whether migrating insects could deduce the mean wind direction from the turbulent fluctuations in temperature. Within the atmospheric boundary-layer, temperature records show characteristic ramp-cliff structures, and insects flying downwind would move through these ramps whilst those flying crosswind would not. However, analysis of vertical-looking radar data on the common orientations of nocturnally migrating insects in the UK produced no evidence that the migrants actually use temperature ramps as orientation cues. This suggests that insects rely on turbulent velocity and acceleration cues, and refocuses attention on how these can be detected, especially as small-scale turbulence is usually held to be directionally invariant (isotropic). In the second part of the paper we present a theoretical analysis and simulations showing that velocity fluctuations and accelerations felt by an insect are predicted to be anisotropic even when the small-scale turbulence (measured at a fixed point or along the trajectory of a fluid-particle) is isotropic. Our results thus provide further evidence that insects do indeed use turbulent velocity and acceleration cues as indicators of the mean wind direction

Biochemical comparison of two Hypostomus populations (Siluriformes, Loricariidae) from the Atlântico Stream of the upper Paraná River basin, Brazil

Two syntopic morphotypes of the genus Hypostomus - H. nigromaculatus and H. cf. nigromaculatus (Atlântico Stream, Paraná State) - were compared through the allozyme electrophoresis technique. Twelve enzymatic systems (AAT, ADH, EST, GCDH, G3PDH, GPI, IDH, LDH, MDH, ME, PGM and SOD) were analyzed, attributing the score of 20 loci, with a total of 30 alleles. Six loci were diagnostic (Aat-2, Gcdh-1, Gpi-A, Idh-1, Ldh-A and Mdh-A), indicating the presence of interjacent reproductive isolation. The occurrence of few polymorphic loci acknowledge two morphotypes, with heterozygosity values He = 0.0291 for H. nigromaculatus and He = 0.0346 for H. cf. nigromaculatus. FIS statistics demonstrated fixation of the alleles in the two morphotypes. Genetic identity (I) and distance (D) of Nei (1978) values were I = 0.6515 and D = 0.4285. The data indicate that these two morphotypes from the Atlântico Stream belong to different species

Peritoneal dialysis prescription in children: bedside principles for optimal practice

There is no unique optimal peritoneal dialysis prescription for all children, although the goals of ultrafiltration and blood purification are universal. In turn, a better understanding of the physiology of the peritoneal membrane, as a dynamic dialysis membrane with an exchange surface area recruitment capacity and unique permeability characteristics, results in the transition from an empirical prescription process based on clinical experience alone to the potential for a personalized prescription with individually adapted fill volumes and dwell times. In all cases, the prescribed exchange fill volume should be scaled for body surface area (ml/m2), and volume enhancement should be conducted based on clinical tolerance and intraperitoneal pressure measurements (IPP; cmH2O). The exchange dwell times should be determined individually and adapted to the needs of the patient, with particular attention to phosphate clearance and ultrafiltration capacity. The evolution of residual kidney function and the availability of new, more physiologic, peritoneal dialysis fluids (PDFs) also influence the prescription process. An understanding of all of these principles is integral to the provision of clinically optimal PD

The Specific Heat of Normal, Degenerate Quark Matter: Non-Fermi Liquid Corrections

In normal degenerate quark matter, the exchange of dynamically screened transverse gluons introduces infrared divergences in the quark self-energies that lead to the breakdown of the Fermi liquid description. If the core of neutron stars are composed of quark matter with a normal component, cooling by direct quark Urca processes may be modified by non-Fermi liquid corrections. We find that while the quasiparticle density of states is finite and non-zero at the Fermi surface, its frequency derivative diverges and results in non-Fermi liquid corrections to the specific heat of the normal, degenerate component of quark matter. We study these non-perturbative non-Fermi liquid corrections to the specific heat and the temperature dependence of the chemical potential and show that these lead to a reduction of the specific heat.Comment: new discussion, updated references, accepted in PR

Cytogenetic analysis of five Hypostomus species (Siluriformes, Loricariidae)

In this work, we analyzed the karyotypes of five Hypostomus species. Hypostomus cf. heraldoi, from the Mogi-Guaçu River, had 2n = 72 chromosomes, with a nucleolar organizer region (NOR) in one chromosomal pair. Hypostomus regani, from the Mogi-Guaçu River had 2n = 72 chromosomes with NORs in two chromosomal pairs. Hypostomus sp., from the Mogi-Guaçu River basin, had 2n = 68 chromosomes, with NORs in two chromosomal pairs. Hypostomus aff. agna, from Cavalo Stream, had 2n = 74 chromosomes with NORs in two chromosomal pairs. Hypostomus cf. topavae, from Carrapato Stream, had 2n = 80 chromosomes, with NORs in two chromosomal pairs. Hypostomus species showed marked diversity in the karyotypic formula, which suggested the occurrence of several Robertsonian rearrangements and pericentric inversions during the evolutionary history of this genus. This hypothesis was supported by the occurrence of a large number of uniarmed chromosomes and multiple NORs in a terminal position in most species and may be a derived condition in the Loricariidae

Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index

Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs. The cfDNA fragments and integrity index significantly differentiated neoplastic versus non-neoplastic dogs (P<0.05), and allowed the distinction between benign and malignant lesions (P<0.05). Even if without statistical significance, the amount of cfDNA was also affected by tumor necrosis and correlated with tumor size and apoptotic markers expression. A significant (P<0.01) increase of Bcl-2 in malignant tumors was observed, and in metastatic CMTs the evasion of apoptosis was also suggested. This study, therefore, provides evidence that cfDNA could be a diagnostic marker in dogs carrying mammary nodules suggesting that its potential application in early diagnostic procedures should be further investigated