A Conserved Role for SNX9-Family Members in the Regulation of Phagosome Maturation during Engulfment of Apoptotic Cells

Clearance of apoptotic cells is of key importance during development, tissue homeostasis and wound healing in multi-cellular animals. Genetic studies in the nematode Caenorhabditis elegans have identified a set of genes involved in the early steps of cell clearance, in particular the recognition and internalization of apoptotic cells. A pathway that orchestrates the maturation of phagosomes containing ingested apoptotic cells in the worm has recently been described. However, many steps in this pathway remain elusive. Here we show that the C. elegans SNX9-family member LST-4 (lateral signaling target) and its closest mammalian orthologue SNX33 play an evolutionary conserved role during apoptotic cell corpse clearance. In lst-4 deficient worms, internalized apoptotic cells accumulated within non-acidified, DYN-1-positive but RAB-5-negative phagosomes. Genetically, we show that LST-4 functions at the same step as DYN-1 during corpse removal, upstream of the GTPase RAB-5. We further show that mammalian SNX33 rescue C. elegans lst-4 mutants and that overexpression of truncated SNX33 fragments interfered with phagosome maturation in a mammalian cell system. Taken together, our genetic and cell biological analyses suggest that LST-4 is recruited through a combined activity of DYN-1 and VPS-34 to the early phagosome membrane, where it cooperates with DYN-1 to promote recruitment/retention of RAB-5 on the early phagosomal membrane during cell corpse clearance. The functional conservation between LST-4 and SNX33 indicate that these early steps of apoptotic phagosome maturation are likely conserved through evolution

Automated Discrimination of Brain Pathological State Attending to Complex Structural Brain Network Properties: The Shiverer Mutant Mouse Case

Neuroimaging classification procedures between normal and pathological subjects are sparse and highly dependent of an expert's clinical criterion. Here, we aimed to investigate whether possible brain structural network differences in the shiverer mouse mutant, a relevant animal model of myelin related diseases, can reflect intrinsic individual brain properties that allow the automatic discrimination between the shiverer and normal subjects. Common structural networks properties between shiverer (C3Fe.SWV Mbpshi/Mbpshi, n = 6) and background control (C3HeB.FeJ, n = 6) mice are estimated and compared by means of three diffusion weighted MRI (DW-MRI) fiber tractography algorithms and a graph framework. Firstly, we found that brain networks of control group are significantly more clustered, modularized, efficient and optimized than those of the shiverer group, which presented significantly increased characteristic path length. These results are in line with previous structural/functional complex brain networks analysis that have revealed topologic differences and brain network randomization associated to specific states of human brain pathology. In addition, by means of network measures spatial representations and discrimination analysis, we show that it is possible to classify with high accuracy to which group each subject belongs, providing also a probability value of being a normal or shiverer subject as an individual anatomical classifier. The obtained correct predictions (e.g., around 91.6–100%) and clear spatial subdivisions between control and shiverer mice, suggest that there might exist specific network subspaces corresponding to specific brain disorders, supporting also the point of view that complex brain network analyses constitutes promising tools in the future creation of interpretable imaging biomarkers

Permanent Electric Dipole Moment Search in 129Xe

A permanent electric dipole moment (EDM) implies breakdown of P (parity) and T (time reversal) symmetries. Provided CPT holds, this implies CP violation. Observation of an EDM at achievable experimental sensitivity would provide unambiguous evidence for physics beyond the Standard Model and limits towards matter-antimatter asymmetry. Our experiment uses differential spin precession of 3He and 129Xe, co-occupying the same volume, to measure the EDM of xenon. We have reached in a first test already sensitivity in the range 10-28 ecm. I will present the current status of the experiment and challenges like long term (weeks) tight control over magnetic and electric fields

Responses to Bacteria, Virus, and Malaria Distinguish the Etiology of Pediatric Clinical Pneumonia

RationalePlasma-detectable biomarkers that rapidly and accurately diagnose bacterial infections in children with suspected pneumonia could reduce the morbidity of respiratory disease and decrease the unnecessary use of antibiotic therapy.ObjectivesUsing 56 markers measured in a multiplexed immunoassay, we sought to identify proteins and protein combinations that could discriminate bacterial from viral or malarial diagnoses.MethodsWe selected 80 patients with clinically diagnosed pneumonia (as defined by the World Health Organization) who also met criteria for bacterial, viral, or malarial infection based on clinical, radiographic, and laboratory results. Ten healthy community control subjects were enrolled to assess marker reliability. Patients were subdivided into two sets: one for identifying potential markers and another for validating them.Measurements and main resultsThree proteins (haptoglobin, tumor necrosis factor receptor 2 or IL-10, and tissue inhibitor of metalloproteinases 1) were identified that, when combined through a classification tree signature, accurately classified patients into bacterial, malarial, and viral etiologies and misclassified only one patient with bacterial pneumonia from the validation set. The overall sensitivity and specificity of this signature for the bacterial diagnosis were 96 and 86%, respectively. Alternative combinations of markers with comparable accuracy were selected by support vector machine and regression models and included haptoglobin, IL-10, and creatine kinase-MB.ConclusionsCombinations of plasma proteins accurately identified children with a respiratory syndrome who were likely to have bacterial infections and who would benefit from antibiotic therapy. When used in conjunction with malaria diagnostic tests, they may improve diagnostic specificity and simplify treatment decisions for clinicians

Mesozoic to recent geological history of southern Crimea and the Eastern Black Sea region

<p>We provide a synthesis of stratigraphic data to unravel the history of the geological evolution of South Crimea in the Mesozoic and Cenozoic. The South Crimea Orogen consists of three major mega-sequences: (1) the Triassic–Early Jurassic; (2) the Aalenian–Bathonian; and (3) the Callovian–Eocene. The Late Triassic–Early Jurassic deposits formed in the environment of a forearc basin and a remnant basin. The Aalenian–Bathonian deposits formed above subduction extension and a volcanic belt. Three main Callovian–Eocene tectonic units can be identified in South Crimea: (1) the South Crimean Shelf Basin; (2) the Sudak Deepwater Trough; and (3) the Alchak–Kaya Shelf Basin at the northern margin of the Shatsky Ridge. The Oligocene–Quaternary deposits are considered to be syn-orogenic. A description of the anticipated stratigraphic units on the Shatsky Ridge is suggested for the Middle Jurassic, Callovian–Late Jurassic, Neocomian, Aptian–Albian, Late Cretaceous–Paleocene, Eocene and Maykopian. We propose a model for the geological history of the Eastern Black Sea Basin. Graben formed during the Late Barremian–Albian at the location of the future Eastern Black Sea Basin and a phase of volcanism occurred in the Albian. The main phase of rifting and spreading of oceanic crust took place during Cenomanian–Santonian time. </p