The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity

Ion channels are well placed to transduce environmental cues into signals used by cells to generate a wide range of responses, but little is known about their role in the regulation of RNA metabolism. Here we show that the TRPV4 cation channel binds the DEAD-box RNA helicase DDX3X and regulates its function. TRPV4-mediated Ca2+ influx releases DDX3X from the channel and drives DDX3X nuclear translocation, a process that involves calmodulin (CaM) and the CaM-dependent kinase II. Genetic depletion or pharmacological inhibition of TRPV4 diminishes DDX3X-dependent functions, including nuclear viral export and translation. Furthermore, TRPV4 mediates Ca2+ influx and nuclear accumulation of DDX3X in cells exposed to the Zika virus or the purified viral envelope protein. Consequently, targeting of TRPV4 reduces infectivity of dengue, hepatitis C and Zika viruses. Together, our results highlight the role of TRPV4 in the regulation of DDX3X-dependent control of RNA metabolism and viral infectivity

Fracturas de extremidad proximal de cubito en el niño

Las fracturas y epifisiolisis proximales de cubito, son lesiones raras y cuando se producen suelen estar mínimamente ó no desplazadas, pudiendo ser tratadas de forma conservadoras. En los casos en que existe desplazamiento significativo, requieren reducción abierta y osteosíntesis. Independientemente del tipo de tratamiento utilizado, el resultado final suele ser satisfactorio. Realizamos un estudio retrospectivo de 13 casos de fractura-epifisiolisis de extremo proximal de cubito, ocurridas durante el periodo 1992-2001. Nuestro objetivo es analizar los resultados obtenidos en el tratamiento de las lesiones y realizar una revisión bibliográfica, teniendo en cuenta los distintos métodos de clasificación, valoración de resultados y las valoraciones descritas para la iniciación de tratamiento quirúrgico de estas lesiones.The epiphysiolisis and proximal lunar fractures in children rare injuries and usually the aren't displaced. In these cases they can be managed nonoperatively. If there's a marked displacement, open reduction and internal fixation is mandatory. The final outcome uses to be successful despite the management; 13 patients with epiphysiolisis or fracture of the proximal ulna between 1992-2001 ere revised. Our aim is to evaluate our outcomes and reviewed the literatur

Lipoma parostal de fémur: Aportación de un caso

Describimos un caso de lipoma parostal de fémur, un tumor benigno poco frecuente formado por tejido adiposo maduro en relación con el periostio. Nuestro objetivo es documentar el caso, comentando los hallazgos radiológicos, histológicos y el tratamiento y realizar una revisión bibliográfica.We describe a case of parosteal lipoma of the femur. It is an infrequent benign neoplasm composed of mature fat, intermately connected with the periosteum. Our aim is to document the case, and comment the radiological, histological findings, and treatment, and review the literature

Epifisiolisis de cabeza de radio asociadas a luxación de codo y reducción espontánea

Realizamos un estudio retrospectivo de 10 casos de la epifisiolisis de cabeza de radio ocurridas durante el periodo 1992 a 1997, con un desplazamiento mayor de 60º que según los criterios de O'Brien corresponderían a un grado III. De todas las revisadas seleccionamos 6 casos en los que había una angulación mayor de 90º, creemos ocurren después de luxación o reducción espontánea de luxación de codo; por ser las más frecuentes, las que más problemas presentan en el tratamiento y las que producen más secuelas. Nuestro objetivo es valorar los resultados obtenidos con nuestros tratamientos y realizar una revisión bibliográfica.We have done a retrospective study of ten cases of radial head epiphysiolysis occurred between 1992 and 1997, displaced more than 60º. (O'Brien's grade III). Amongst them we have selected those which were displaced more than 90º (six cases) probably occurred after an elbow luxation or after the spontaneous reduction of an elbow luxation; because the are more infrequent, more troublesome and they give more secuelae. Our aim is to evaluate the results obtained with the treatment and to review the literature

Identification of biomarkers for the antiangiogenic and antitumour activity of the superoxide dismutase 1 (SOD1) inhibitor tetrathiomolybdate (ATN-224)

Tetrathiomolybdate (choline salt; ATN-224), a specific, high-affinity copper binder, is currently being evaluated in several phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase 1 (SOD1) leading to antiangiogenic and antitumour effects. The pharmacodynamics of tetrathiomolybdate has been followed by tracking ceruloplasmin (Cp), a biomarker for systemic copper. However, at least in mice, the inhibition of angiogenesis occurs before a measurable decrease in systemic copper is observed. Thus, the identification and characterisation of other biomarkers to follow the activity of ATN-224 in the clinic is of great interest. Here, we present the preclinical evaluation of two potential biomarkers for the activity of ATN-224: (i) SOD activity measurements in blood cells in mice and (ii) levels of endothelial progenitor cells (EPCs) in bonnet macaques treated with ATN-224. The superoxide dismutase activity in blood cells in mice is rapidly inhibited by ATN-224 treatment at doses at which angiogenesis is maximally inhibited. Furthermore, ATN-224 dosing in bonnet macaques causes a profound and reversible decrease in EPCs without significant toxicity. Thus, both SOD activity measurements and levels of EPCs may be useful biomarkers of the antiangiogenic activity of ATN-224 to be used in its clinical development

RNA-Seq Reveals an Integrated Immune Response in Nucleated Erythrocytes

Background: Throughout the primary literature and within textbooks, the erythrocyte has been tacitly accepted to have maintained a unique physiological role; namely gas transport and exchange. In non-mammalian vertebrates, nucleated erythrocytes are present in circulation throughout the life cycle and a fragmented series of observations in mammals support a potential role in non-respiratory biological processes. We hypothesised that nucleated erythrocytes could actively participate via ligand-induced transcriptional re-programming in the immune response. Methodology/Principal Findings: Nucleated erythrocytes from both fish and birds express and regulate specific pattern recognition receptor (PRR) mRNAs and, thus, are capable of specific pathogen associated molecular pattern (PAMP) detection that is central to the innate immune response. In vitro challenge with diverse PAMPs led to de novo specific mRNA synthesis of both receptors and response factors including interferon-alpha (IFNα) that exhibit a stimulus-specific polysomal shift supporting active translation. RNA-Seq analysis of the PAMP (Poly (I:C), polyinosinic:polycytidylic acid)-erythrocyte response uncovered diverse cohorts of differentially expressed mRNA transcripts related to multiple physiological systems including the endocrine, reproductive and immune. Moreover, erythrocyte-derived conditioned mediums induced a type-1 interferon response in macrophages thus supporting an integrative role for the erythrocytes in the immune response. Conclusions/Significance: We demonstrate that nucleated erythrocytes in non-mammalian vertebrates spanning significant phylogenetic distance participate in the immune response. RNA-Seq studies highlight a mRNA repertoire that suggests a previously unrecognized integrative role for the erythrocytes in other physiological systems

Comparative (Meta)genomic Analysis and Ecological Profiling of Human Gut-Specific Bacteriophage φB124-14

Bacteriophage associated with the human gut microbiome are likely to have an important impact on community structure and function, and provide a wealth of biotechnological opportunities. Despite this, knowledge of the ecology and composition of bacteriophage in the gut bacterial community remains poor, with few well characterized gut-associated phage genomes currently available. Here we describe the identification and in-depth (meta)genomic, proteomic, and ecological analysis of a human gut-specific bacteriophage (designated φB124-14). In doing so we illuminate a fraction of the biological dark matter extant in this ecosystem and its surrounding eco-genomic landscape, identifying a novel and uncharted bacteriophage gene-space in this community. φB124-14 infects only a subset of closely related gut-associated Bacteroides fragilis strains, and the circular genome encodes functions previously found to be rare in viral genomes and human gut viral metagenome sequences, including those which potentially confer advantages upon phage and/or host bacteria. Comparative genomic analyses revealed φB124-14 is most closely related to φB40-8, the only other publically available Bacteroides sp. phage genome, whilst comparative metagenomic analysis of both phage failed to identify any homologous sequences in 136 non-human gut metagenomic datasets searched, supporting the human gut-specific nature of this phage. Moreover, a potential geographic variation in the carriage of these and related phage was revealed by analysis of their distribution and prevalence within 151 human gut microbiomes and viromes from Europe, America and Japan. Finally, ecological profiling of φB124-14 and φB40-8, using both gene-centric alignment-driven phylogenetic analyses, as well as alignment-free gene-independent approaches was undertaken. This not only verified the human gut-specific nature of both phage, but also indicated that these phage populate a distinct and unexplored ecological landscape within the human gut microbiome

Noise levels of multi-rotor unmanned aerial vehicles with implications for potential underwater impacts on marine mammals

Despite the rapid increase in the use of unmanned aerial vehicles (UAVs) in marine mammal research, knowledge of the effects of UAVs on study animals is very limited. We recorded the in-air and in-water noise from two commonly used multi-rotor UAVs, the SwellPro Splashdrone and the DJI Inspire 1 Pro, to assess the potential for negative noise effects of UAV use. The Splashdrone and Inspire UAVs produced broad-band in-air source levels of 80 dB re 20 μPa and 81 dB re 20 μPa (rms), with fundamental frequencies centered at 60 Hz and 150 Hz. The noise of the UAVs coupled poorly into the water, and could only be quantified above background noise of the recording sites at 1 m depth when flying at altitudes of 5 and 10 m, resulting in broad-band received levels around 95 dB re μPa rms for the Splashdrone and around 101 dB re μPa rms for the Inspire. The third octave levels of the underwater UAV noise profiles are (i) close to ambient noise levels in many shallow water habitats, (ii) largely below the hearing thresholds at low frequencies of toothed whales, but (iii) likely above the hearing thresholds of baleen whales and pinnipeds. So while UAV noise may be heard by some marine mammals underwater, it is implied that the underwater noise effect is small, even for animals close to the water surface. Our findings will be valuable for wildlife managers and regulators when issuing permits and setting guidelines for UAV operations. Further, our experimental setup can be used by others to evaluate noise effects of larger sized UAVs on marine mammal

Retinal afferents on Golgi-identified vertical neurons in the superior colliculus of the rabbit. A Golgi-EM,

The characteristics and distribution pattem of retinal afferent terminals making synaptic contacts on narrow field vertical neurons in the stratum griseum superficiale of the rabbit superior colliculus were studied using the Golgi-gold substitution technique in combination with either autoradiographic or degenerative methods. At the level of light microscopy, identified gold-toned vertical neurons showed similar features to those previously described by others. Although their axons were frequently seen rising from the basal dendritic tuft, they could also emerge from an apical dendrite, but rarely from the cell body. The electron rnicroscopic study revealed that these neurons received radiolabelled or degenerated profiles with typical features of retinal terminals, while more proximal parts seemed to receive fewer terminals but of larger size. Axo-somatic synaptic junctions were very rare and, interestingly, retinal terminals were not seen forming synapses on the basal dendritic arborization. The present results indicate that the narrow field vertical cells are targets for retinotectal projection

Distribution of cortico-visual neurons projecting to the pons in the cat. A retrograde labelling study with rhodamine latex microspheres

Injections of the low diffusion retrograde tracer rhodamine latex microspheres were made in the pontine grey matter of the cat in order to study the cortical convergence to the pons. We found a different distribution of cells in the convex surface of the brain hemisphere making ventral os dorsolateral injections. In the first case, cells were grouped in the top of the gyri. In the second case, cells were more frequent in the bottom of the sulci. Our results show a possible retinotopic organization of this projection