Whole genome sequencing identifies a cryptic SOX9 regulatory element duplication underlying a case of 46,XX ovotesticular difference of sexual development.

Ovotesticular differences of sexual development (OT-DSD) are rare genetic variances defined by the coexistence of both testicular and ovarian tissues. Various molecular etiologies including SRY translocation or SOX9 pathogenic variants with different modes of inheritance have been associated with 46,XX OT-DSD. Here we describe a child diagnosed with SRY-negative 46,XX OT-DSD after completing a series of complex clinical genetic analyses, including chromosomal microarray, DSD gene panel (sequencing and deletion/duplication analysis), whole exome sequencing, and whole genome sequencing. Of these, only whole genome sequencing reported a pathogenic duplication in a non-coding region that contains the RevSex regulatory element, which modifies SOX9 expression and is associated with 46,XX OT-DSD and complete sex reversal. This is the first clinical RevSex duplication detected by clinical whole genome sequencing. We highlight the utility of whole genome sequencing in shortening the diagnostic odyssey and the importance of optimal counseling through a team-based multi-specialty approach for patients with DSDs.

Volumetric characterisation of waste deposits generated during the production of fertiliser derived from phosphoric rock by using LiDAR and electrical resistivity tomography.

The lack of environmental regulations before 1998 brought about significant ecological consequences in Europe. There are 4,000,000 ha potentially contaminated by waste, resulting from industrial activity. These sites present abnormal values of salinity, alkalinity, and organic and inorganic pollutants. A representative example of this is the production of fertiliser derived from phosphoric rock through the wet acid process which mainly produces phosphogypsum and pyrite ashes. For each tonne of fertiliser produced, five tonnes of phosphogypsum are generated, which in most of the cases were simply piled into non-conditionate deposits; currently, there is no information about these deposits. Hence, fast and affordable methodologies should be developed to calculate the volume contained in the existing waste deposits. Thus, this study aims to: i) scan the industrial area selected in order to identify the distribution and possible variants of the waste that make up the configuration of geoelectrical profiles and boreholes, and ii) accurately determine the volume contained in the chosen deposits by merging Electrical Resistivity Tomography with LiDAR point cloud. Results show a range of deposit volumes that run from 4900 m3 to 59,300 m3. The density of LiDAR point cloud (1 point/m2) ensures metric precision for the superficial layer. The Electrical Resistivity Tomography revealed the geometry of the deposits that superposes two layers marking the border between waste and natural terrain, and the boreholes guarantee the exactness of the waste layer thickness. This synergistic combination of Electrical Resistivity Tomography with LiDAR point cloud yields an accurate method that we used to calculate the volume of waste present in the deposits.

Enhancing Electrical Contact with a Commercial Polymer for Electrical Resistivity Tomography on Archaeological Sites: A Case Study.

This communication reports an improvement of the quality of the electrical data obtained from the application of electrical resistivity tomography method on archaeological studies. The electrical contact between ground and electrode enhances significantly by using carbomer-based gel during the electrical resistivity tomography measurements. Not only does the gel promote the conservation of the building surface under investigation, but it also virtually eliminates the necessity of conventional spike electrodes, which in many archaeological studies are inadequate or not permitted. Results evidenced an enhancement in the quality of the electrical data obtained in the order of thousands of units compared with those without using the carbomer-based gel. The potential and capabilities of this affordable gel make it appropriate to be applied to other geoelectrical studies beyond archaeological investigations. Moreover, it might solve corrosion issues on conventional spike electrodes, and electrical multicore cables usually provoked for added saltwater attempting to improve the electrical contact.

Bone morphogenic protein-4 induces hypertension in mice: role of noggin, vascular NADPH oxidases, and impaired vasorelaxation.

BACKGROUND: Recent in vitro studies have shown that disturbed flow and oxidative conditions induce the expression of bone morphogenic proteins (BMPs 2 and 4) in cultured endothelial cells. BMPs can stimulate superoxide production and inflammatory responses in endothelial cells, raising the possibility that BMPs may play a role in vascular diseases such as hypertension and atherosclerosis. In this study, we examined the hypothesis that BMP4 would induce hypertension in intact animals by increasing superoxide production from vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and an impairment of vasodilation responses. METHODS AND RESULTS: BMP4 infusion by osmotic pumps increased systolic blood pressure in a time- and dose-dependent manner in both C57BL/6 mice (from 101 to 125 mm Hg) and apolipoprotein E-null mice (from 107 to 146 mm Hg) after 4 weeks. Cotreatment with the BMP antagonist noggin or the NADPH oxidase inhibitor apocynin completely blocked the BMP4 effect. In addition, BMP4 infusion stimulated aortic NADPH oxidase activity and impaired vasorelaxation, both of which were prevented either by coinfusing noggin or by treating the isolated aortas with apocynin. BMP4, however, did not cause significant changes in maximum relaxation induced by the endothelium-independent vasodilator nitroglycerin. Remarkably, BMP4 infusion failed to stimulate aortic NADPH oxidases, increase blood pressure, and impair vasodilation responses in p47phox-deficient mice. CONCLUSIONS: These results suggest that BMP4 infusion induces hypertension in mice in a vascular NADPH oxidase-dependent manner and the subsequent endothelial dysfunction. We suggest that BMP4 is a novel mediator of endothelial dysfunction and hypertension and that noggin and its analogs could be used as therapeutic agents for treating vascular diseases.