Is a low sacral ratio associated with primary vesicoureteral reflux in children?

Introduction: The association of sacral anomalies with fecal incontinence and lower urinary tract dysfunction is known. The sacral ratio is proposed as a tool for evaluation of sacral development. The aim of this cross-sectional study was to evaluate the prevalence and severity of vesicoureteral reflux in children with a low sacral ratio. Materials and Methods: Six hundred and sixty nine children who were referred to a radiology clinic for a standard (fluoroscopic) VCUG to detect vesicoureteral reflux and other anomalies of the lower urinary tract after an episode of urinary tract infection were included in the study and their sacral ratios were measured. Results: All children were younger than 14 years of age (mean 3.44±3.20). Of 669 children, 593 (88.6%) had normal sacral ratios out of whom 423 (71.3%) did not have VUR and 170 (28.7%) had VUR. Seventy-six (11.3%) children out of 669 cases had low sacral ratios; 49 (64.5%) of them had no VUR and 27 (35.5%) had VUR. There was no significant difference in the prevalence of VUR between children with and without a low sacral ratio (p value=0.217). Also, there was no significant difference or trend between a low sacral ratio and the severity of reflux (Chi2 for trend). Conclusions: Although sacral anomalies may be related to some cases of VUR by producing lower urinary tract dysfunction, the sacral ratio is not associated with VUR

Modulation of conotoxin structure and function is achieved through a multienzyme complex in the venom glands of cone snails

pre-printBackground: Conotoxins can be utilized to investigate enzyme-assisted folding of disulfide-rich peptides. Results: Various ER-resident cone snail enzymes act in concert to accelerate the oxidative folding of conotoxins and modulate their conformation by reconfiguring disulfide connectivities. Conclusion: The folding of conotoxins is a tightly regulated multienzyme-assisted process. Significance: Modulation of the conformation of conotoxins increases their molecular and functional diversity

Identification of Conus peptidylprolyl cis-trans isomerases (PPIases) and assessment of their role in the oxidative folding of conotoxins

Journal ArticlePeptidylprolyl cis-trans isomerases (PPIases) are ubiquitous proteins that catalyze the cis-trans isomerization of prolines. A number of proteins, such as Drosophila rhodopsin and the human immunodeficiency viral protein HIV-1 Gag, have been identified as endogenous substrates for PPIases. However, very little is known about the interaction of PPIases with small, disulfide- rich peptides. Marine cone snails synthesize a wide array of cysteine-rich peptides, called conotoxins, many of which contain one or more prolines or hydroxyprolines. To identify whether PPIase-associated cis-trans isomerization of these residues affects the oxidative folding of conotoxins, we identified, sequenced, and expressed three functionally active isoforms of PPIase from the venom gland of Conus novaehollandiae, and we characterized their ability to facilitate oxidative folding of conotoxins in vitro. Three conotoxins, namely ?-GIIIA,?-SIIIA, and ?-MVIIC, derived from two distinct toxin gene families were assayed. Conus PPIase significantly increased the rate of appearance of the native form of ?-GIIIA, a peptide containing three hydroxyprolines. In contrast, the presence of PPIase had no effect on the folding of ?-SIIIA and ?-MVIIC, peptides containing no or one proline residue, respectively.Wefurther showed that an endoplasmic reticulum-resident PPIase isoform facilitated folding of ?-GIIIA more efficiently than two cytosolic isoforms. This is the first study to demonstrate PPIase-assisted folding of conotoxins, small disulfide-rich peptides with unique structural properties

Combined proteomic and transcriptomic interrogation of the venom gland of conus geographus uncovers novel components and functional compartmentalization

pre-printCone snails are highly successful marine predators that use complex venoms to capture prey. At any given time, hundreds of toxins (conotoxins) are synthesized in the secretory epithelial cells of the venom gland, a long and convoluted organ that can measure 4 times the length of the snail's body. In recent years a number of studies have begun to unveil the transcriptomic, proteomic and peptidomic complexity of the venom and venom glands of a number of cone snail species. By using a combination of DIGE, bottom-up proteomics and next-generation transcriptome sequencing the present study identifies proteins involved in envenomation and conotoxin maturation, significantly extending the repertoire of known (poly)peptides expressed in the venom gland of these remarkable animals. We interrogate the molecular and proteomic composition of different sections of the venom glands of 3 specimens of the fish hunter Conus geographus and demonstrate regional variations in gene expression and protein abundance. DIGE analysis identified 1204 gel spots of which 157 showed significant regional differ- ences in abundance as determined by biological variation analysis. Proteomic interrogation identified 342 unique proteins including those that exhibited greatest fold change. The majority of these proteins also exhibited sig- nificant changes in their mRNA expression levels validat- ing the reliability of the experimental approach. Transcriptome sequencing further revealed a yet unknown genetic diversity of several venom gland components. Interestingly, abundant proteins that potentially form part of the injected venom mixture, such as echotoxins, phospholipase A2 and con-ikots-ikots, classified into distinct expression clusters with expression peaking in different parts of the gland. Our findings significantly enhance the known repertoire of venom gland polypeptides and provide molecular and biochemical evidence for the compartmentalization of this organ into distinct functional entities

Plane-Strain Surface Waves in a Laminated Composite

Elastic wave propagation in plane strain in a periodically layered half space is considered, with the layering parallel to the bounding traction-free plane. Attention is focused on surface waves of the Rayleigh-type propagating parallel to the bounding plane. It is found that such waves are highly dispersive and that higher branches may be discontinuous. Introduction We are concerned here with a periodically layered half space which is formed by an infinite number of cells and bounded by a traction-free plane which is parallel to the layering, whose location with respect to the cell structure, however, is arbitrary. Each cell consists of two layers of different materials and different thicknesses, perfectly bonded together, which are, however, assumed to be homogeneous, isotropic, and linearly elastic. In considering propagation of horizontally polarized shear waves (i.e., SH waves involving a state of antiplane strain) it has been recently shown It is the purpose of the present work to consider the propagation of compressional and vertically polarized shear waves (i.e., P and SF waves involving a state of plane strain). The work is based on results of recent analyses of wave solutions in plane strain obtained for an infinite layered medium, again by applying Floquet's theorem Emphasis is placed on determining properties of Rayleightype surface waves propagating parallel to the bounding plane. For this purpose, an infinite periodically layered medium is considered first and the associated dispersion equation is briefly discussed. Next, the condition is imposed that some plane parallel to the layering be traction-free, which leads to the problem of reflection at a free boundary. Different types of waves in a half-space are discussed in the folowing section, and then narrowed down to a consideratio

Patch-based structural masking model with an application to compression

The ability of an image region to hide or mask a given target signal continues to play a key role in the design of numerous image processing and vision systems. However, current state-of-the-art models of visual masking have been optimized for artificial targets placed upon unnatural backgrounds. In this paper, we (1) measure the ability of natural-image patches in masking distortion; (2) analyze the performance of a widely accepted standard masking model in predicting these data; and (3) report optimal model parameters for different patch types (textures, structures, and edges). Our results reveal that the standard model of masking does not generalize across image type; rather, a proper model should be coupled with a classification scheme which can adapt the model parameters based on the type of content contained in local image patches. The utility of this adaptive approach is demonstrated via a spatially adaptive compression algorithm which employs patch-based classification. Despite the addition of extra side information and the high degree of spatial adaptivity, this approach yields an efficient wavelet compression strategy that can be combined with very accurate rate-control procedures.Peer reviewedElectrical and Computer Engineerin

Ero1-Mediated Reoxidation of Protein Disulfide Isomerase Accelerates the Folding of Cone Snail Toxins

Disulfide-rich peptides are highly abundant in nature and their study has provided fascinating insight into protein folding, structure and function. Venomous cone snails belong to a group of organisms that express one of the largest sets of disulfide-rich peptides (conotoxins) found in nature. The diversity of structural scaffolds found for conotoxins suggests that specialized molecular adaptations have evolved to ensure their efficient folding and secretion. We recently showed that canonical protein disulfide isomerase (PDI) and a conotoxin-specific PDI (csPDI) are ubiquitously expressed in the venom gland of cone snails and play a major role in conotoxin folding. Here, we identify cone snail endoplasmic reticulum oxidoreductin-1 (Conus Ero1) and investigate its role in the oxidative folding of conotoxins through reoxidation of cone snail PDI and csPDI. We show that Conus Ero1 preferentially reoxidizes PDI over csPDI, suggesting that the reoxidation of csPDI may rely on an Ero1-independent molecular pathway. Despite the preferential reoxidation of PDI over csPDI, the combinatorial effect of Ero1 and csPDI provides higher folding yields than Ero1 and PDI. We further demonstrate that the highest in vitro folding rates of two model conotoxins are achieved when all three enzymes are present, indicating that these enzymes may act synergistically. Our findings provide new insight into the generation of one of the most diverse classes of disulfide-rich peptides and may improve current in vitro approaches for the production of venom peptides for pharmacological studies

alpha M-Conotoxin MIIIJ Blocks Nicotinic Acetylcholine Receptors at Neuromuscular Junctions of Frog and Fish

We report the discovery and functional characterization of αM-Conotoxin MIIIJ, a peptide from the venom of the fish-hunting cone snail Conus magus. Injections of αM-MIIIJ induced paralysis in goldfish (Carassius auratus) but not mice. Intracellular recording from skeletal muscles of fish (C. auratus) and frog (Xenopus laevis) revealed that αM-MIIIJ inhibited postsynaptic nicotinic acetylcholine receptors (nAChRs) with an IC50 of ~0.1 μM. With comparable potency, αM-MIIIJ reversibly blocked ACh-gated currents (IACh) of voltage-clamped X. laevis oocytes exogenously expressing nAChRs cloned from zebrafish (Danio rerio) muscle. αM-MIIIJ also protected against slowly-reversible block of IACh by α-bungarotoxin (α-BgTX, a snake neurotoxin) and α-conotoxin EI (α-EI, from Conus ermineus another fish hunter) that competitively block nAChRs at the ACh binding site. Furthermore, assessment by fluorescence microscopy showed that αM-MIIIJ inhibited the binding of fluorescently-tagged α-BgTX at neuromuscular junctions of X. laevis, C. auratus, and D. rerio. (Note, we observed that αM-MIIIJ can block adult mouse and human muscle nAChRs exogenously expressed in X. laevis oocytes, but with IC50s ~100-times higher than those of zebrafish nAChRs.) Taken together, these results indicate that αM-MIIIJ inhibits muscle nAChRs and furthermore apparently does so by interfering with the binding of ACh to its receptor. Comparative alignments with homologous sequences identified in other fish hunters revealed that αM-MIIIJ defines a new class of muscle nAChR inhibitors from cone snails

Venom insulins of cone snails diversify rapidly and track prey taxa

A specialized insulin was recently found in the venom of a fish-hunting cone snail, Conus geographus. Here we show that many worm-hunting and snail-hunting cones also express venom insulins, and that this novel gene family has diversified explosively. Cone snails express a highly conserved insulin in their nerve ring; presumably this conventional signaling insulin is finely tuned to the Conus insulin receptor, which also evolves very slowly. By contrast, the venom insulins diverge rapidly, apparently in response to biotic interactions with prey and also possibly the cones’ own predators and competitors. Thus, the inwardly directed signaling insulins appear to experience predominantly purifying sele\ction to target an internal receptor that seldom changes, while the outwardly directed venom insulins frequently experience directional selection to target heterospecific insulin receptors in a changing mix of prey, predators and competitors. Prey insulin receptors may often be constrained in ways that prevent their evolutionary escape from targeted venom insulins, if amino-acid substitutions that result in escape also degrade the receptor’s signaling functions