The Class of Absolute Decomposable Inequality Measures

We provide a parsimonious axiomatisation of the complete class of absolute nequalityindices. Our approach uses only a weak form of decomposability and does not require a priori that the measures be differentiable.inequality measures, decomposability, translation invariance

Palmitoylation Affects the Interaction of Animal Toxins with Sodium Channels

PRISMS 2009 Flow Diagram. Flow chart of data extraction process. (DOC 64 kb

Pulmonary edema as a postoperative complication in two obese patients (a horse and a dog)

In this case series, the development and successful treatment of pulmonary edema are described in two obese animals (a horse and a dog) in the postoperative period. This rare but severe complication is normally fairly easy to diagnose, but the cause is usually multifactorial and difficult to determine. Potentially contributing factors are discussed. Both animals responded successfully to therapy and were discharged without further incidents

An heuristic filtering tool to identify phenotype-associated genetic variants applied to human intellectual disability and canine coat colors

Background: Identification of one or several disease causing variant(s) from the large collection of variants present in an individual is often achieved by the sequential use of heuristic filters. The recent development of whole exome sequencing enrichment designs for several non-model species created the need for a species-independent, fast and versatile analysis tool, capable of tackling a wide variety of standard and more complex inheritance models. With this aim, we developed "Mendelian", an R-package that can be used for heuristic variant filtering. Results: The R-package Mendelian offers fast and convenient filters to analyze putative variants for both recessive and dominant models of inheritance, with variable degrees of penetrance and detectance. Analysis of trios is supported. Filtering against variant databases and annotation of variants is also included. This package is not species specific and supports parallel computation. We validated this package by reanalyzing data from a whole exome sequencing experiment on intellectual disability in humans. In a second example, we identified the mutations responsible for coat color in the dog. This is the first example of whole exome sequencing without prior mapping in the dog. Conclusion: We developed an R-package that enables the identification of disease-causing variants from the long list of variants called in sequencing experiments. The software and a detailed manual are available at https://github.com/BartBroeckx/Mendelian

Anesthetic management for the correction of a patent ductus arteriosus by means of either surgical ligation or transarterial occlusion in dogs

Patent ductus arteriosus (PDA) is one of the most common congenital vascular abnormalities in the dog. In veterinary medicine, surgical ligation (SL) and transarterial occlusion (TO) are two possible treatments that require general anesthesia. Two 4-month-old dogs were anesthetized for the correction of PDA, one by SL and the other by TO. Two different anesthetic and analgesic protocols were used, and were chosen to avoid potential complications. This case report describes two possible anesthetic approaches for PDA corrective surgery (SL and TO)

A disease mutation reveals a role for Nav1.9 in acute itch

Itch (pruritis) and pain represent two distinct sensory modalities; yet both have evolved to alert us to potentially harmful external stimuli. Compared with pain, our understanding of itch is still nascent. Here, we report a new clinical case of debilitating itch and altered pain perception resulting from the heterozygous de novo p.L811P gain-of-function mutation in Na(V)1.9, a voltage-gated sodium (Na-V) channel subtype that relays sensory information from the periphery to the spine. To investigate the role of Na(V)1.9 in itch, we developed a mouse line in which the channel is N-terminally tagged with a fluorescent protein, thereby enabling the reliable identification and biophysical characterization of Na(V)1.9-expressing neurons. We also assessed Na(V)1.9 involvement in itch by using a newly created Na(V)1.9(-/-) and Na(V)1.9(L799P/WT) mouse model. We found that Na(V)1.9 is expressed in a subset of nonmyelinated, nonpeptidergic small-diameter dorsal root ganglia (DRGs). In WT DRGs, but not those of Na(V)1.9(-/-) mice, pruritogens altered action potential parameters and Na-V channel gating properties. Additionally, Na(V)1.9(-/-) mice exhibited a strong reduction in acute scratching behavior in response to pruritogens, whereas Na(V)1.9(L799P/WT) mice displayed increased spontaneous scratching. Altogether, our data suggest an important contribution of Na(V)1.9 to itch signaling

Functional Properties and Toxin Pharmacology of a Dorsal Root Ganglion Sodium Channel Viewed through its Voltage Sensors

The voltage-activated sodium (Nav) channel Nav1.9 is expressed in dorsal root ganglion (DRG) neurons where it is believed to play an important role in nociception. Progress in revealing the functional properties and pharmacological sensitivities of this non-canonical Nav channel has been slow because attempts to express this channel in a heterologous expression system have been unsuccessful. Here, we use a protein engineering approach to dissect the contributions of the four Nav1.9 voltage sensors to channel function and pharmacology. We define individual S3b–S4 paddle motifs within each voltage sensor, and show that they can sense changes in membrane voltage and drive voltage sensor activation when transplanted into voltage-activated potassium channels. We also find that the paddle motifs in Nav1.9 are targeted by animal toxins, and that these toxins alter Nav1.9-mediated currents in DRG neurons. Our results demonstrate that slowly activating and inactivating Nav1.9 channels have functional and pharmacological properties in common with canonical Nav channels, but also show distinctive pharmacological sensitivities that can potentially be exploited for developing novel treatments for pain

The scorpion Toxin Tf2 from Tityus fasciolatus Promotes Nav1.3 opening

We identified Tf2, the first β-scorpion toxin from the venom of the Brazilian scorpion Tityus fasciolatus. Tf2 is identical to Tb2-II found in Tityus bahiensis.We found that Tf2 selectively activates human (h)Nav1.3, a neuronal voltage-gated sodium (Nav) subtype implicated in epilepsy and nociception. Tf2 shifts hNav1.3 activation voltage to more negative values, thereby opening the channel at resting membrane potentials. Seven other tested mammalian Nav channels (Nav1.1-1.2; Nav1.4-1.8) expressed in Xenopus oocytes are insensitive upon application of 1 μM Tf2. Therefore, the identification of Tf2 represents a unique addition to the repertoire of animal toxins that can be used to investigate Nav channel function

From foe to friend: using animal toxins to investigate ion channel function

Ion channels are vital contributors to cellular communication in a wide range of organisms, a distinct feature that renders this ubiquitous family of membrane-spanning proteins a prime target for toxins found in animal venom. For many years, the unique properties of these naturally-occurring molecules have enabled researchers to probe the structural and functional features of ion channels and to define their physiological roles in normal and diseased tissues. To illustrate their considerable impact on the ion channel field, this review will highlight fundamental insights into toxin-channel interactions as well as recently developed toxin screening methods and practical applications of engineered toxins