The battle over Syria's reconstruction

Reconstruction is becoming the new battleground in the Syrian conflict—its continuation by other means. It is instrumentalized by the regime as a way to reconsolidate its control over the country and by rival regional and international powers to shape the internal balance of power and establish spheres of influence in the country. The paper examines the Asad regime’s practices, including co-optation of militia leaders via reconstruction concessions and use of reconstruction to clear strategic areas of opposition-dominated urban settlements. The paper then surveys how the geopolitical struggle in Syria has produced an asymmetry as regards reconstruction: those powers that lost the geo-political contest on the ground seek to use geo-economic superiority to reverse the geo-political outcome. Then the impact of proxy wars and spheres of influence in the country on the security context for reconstruction is examined. Finally, the reconstruction initiatives of the various external parties are assessed, including Russia, Iran and Turkey as well as the spoiler role by which the US seeks to obstruct reconstruction that would spell victory in Syria for its Russian and Iranian rivals.PostprintPeer reviewe

Glomerulocystic kidney disease

Glomerulocystic disease is a rare renal cystic disease with a long descriptive history. Findings from recent studies have significantly advanced the pathophysiological understanding of the disease processes leading to this peculiar phenotype. Many genetic syndromes associated with glomerulocystic disease have had their respective proteins localized to primary cilia or centrosomes. Transcriptional control of renal developmental pathways is dysregulated in obstructive diseases that also lead to glomerulocystic disease, emphasizing the importance of transcriptional choreography between renal development and renal cystic disease

Enhanced diagnostic yield in Meckel-Gruber and Joubert syndrome through exome sequencing supplemented with split-read mapping

Background The widespread adoption of high-throughput sequencing technologies by genetic diagnostic laboratories has enabled significant expansion of their testing portfolios. Rare autosomal recessive conditions have been a particular focus of many new services. Here we report a cohort of 26 patients referred for genetic analysis of Joubert (JBTS) and Meckel-Gruber (MKS) syndromes, two clinically and genetically heterogeneous neurodevelopmental conditions that define a phenotypic spectrum, with MKS at the severe end. Methods Exome sequencing was performed for all cases, using Agilent SureSelect v5 reagents and Illumina paired-end sequencing. For two cases medium-coverage (9×) whole genome sequencing was subsequently undertaken. Results Using a standard analysis pipeline for the detection of single nucleotide and small insertion or deletion variants, molecular diagnoses were confirmed in 12 cases (4 %). Seeking to determine whether our cohort harboured pathogenic copy number variants (CNV), in JBTS- or MKS-associated genes, targeted comparative read-depth analysis was performed using FishingCNV. These analyses identified a putative intragenic AHI1 deletion that included three exons spanning at least 3.4 kb and an intergenic MPP4 to TMEM237 deletion that included exons spanning at least 21.5 kb. Whole genome sequencing enabled confirmation of the deletion-containing alleles and precise characterisation of the mutation breakpoints at nucleotide resolution. These data were validated following development of PCR-based assays that could be subsequently used for “cascade” screening and/or prenatal diagnosis. Conclusions Our investigations expand the AHI1 and TMEM237 mutation spectrum and highlight the importance of performing CNV screening of disease-associated genes. We demonstrate a robust increasingly cost-effective CNV detection workflow that is applicable to all MKS/JBTS referrals

A meckelin-filamin a interaction mediates ciliogenesis

MKS3, encoding the transmembrane receptor meckelin, is mutated in Meckel-Gruber syndrome (MKS), an autosomal-recessive ciliopathy. Meckelin localizes to the primary cilium, basal body and elsewhere within the cell. Here, we found that the cytoplasmic domain of meckelin directly interacts with the actin-binding protein filamin A, potentially at the apical cell surface associated with the basal body. Mutations in FLNA, the gene for filamin A, cause periventricular heterotopias. We identified a single consanguineous patient with an MKS-like ciliopathy that presented with both MKS and cerebellar heterotopia, caused by an unusual in-frame deletion mutation in the meckelin C-terminus at the region of interaction with filamin A. We modelled this mutation and found it to abrogate the meckelin-filamin A interaction. Furthermore, we found that loss of filamin A by siRNA knockdown, in patient cells, and in tissues from Flna Dilp2 null mouse embryos results in cellular phenotypes identical to those caused by meckelin loss, namely basal body positioning and ciliogenesis defects. In addition, morpholino knockdown of flna in zebrafish embryos significantly increases the frequency of dysmorphology and severity of ciliopathy developmental defects caused by mks3 knockdown. Our results suggest that meckelin forms a functional complex with filamin A that is disrupted in MKS and causes defects in neuronal migration and Wnt signalling. Furthermore, filamin A has a crucial role in the normal processes of ciliogenesis and basal body positioning. Concurrent with these processes, the meckelin-filamin A signalling axis may be a key regulator in maintaining correct, normal levels of Wnt signalling. © The Author 2011. Published by Oxford University Press. All rights reserved

A tomographic imagery segmentation methodology for three-phase geomaterials based on simultaneous region growing

X-Ray Computed Tomography (X-Ray CT) is a powerful non-destructive technique used in many domains to obtain the three-dimensional representation of objects, starting from the reconstitution of two-dimensional images of radiographic scanning. This technique is now able to analyze objects within a few microns resolution. Consequently, X-Ray micro-computed tomography (X-Ray μCT) opens perspectivesfor the analysis of the fabric of multi-phase geomaterials such as soils, concretes, rocks or ceramics. To be able to characterize the spatial distribution of the different phases in such complex and disordered materials, automated phase recognition has to be implemented through image segmentation. A crucial difficulty in segmenting images lies in the presence of noise in the obtained tomographic representation, making it difficult to assign a specific phase to each voxel (vx) of the image. In the present study, simultaneous region growing is used to reconstitute the three-dimensional segmented image of granular materials. First, based on a set of expected phases in the image, regions where specific phases are sure to be present are identified, leaving uncertain regions of the image unidentified. Subsequently, the identified regions are grown until growing phases meet each other with vanishing unidentified regions. The methodrequires a limited number of manual parameters that are easily determined. The developed method is illustrated based on three applications on granular materials, comparing the phase volume fractions obtained by segmentation with macroscopic data. It is demonstrated that the algorithm rapidly converges and fills the image after a few iterations.SCOPUS: ar.jinfo:eu-repo/semantics/publishe