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

An examination of unrestricted line women officers' carrer patterns and related issues

With the increasing participation of women in the Naval Service, it is incumbent upon the Navy to provide meaningful utilization of these women. Women officer career development/ career patterns are of significant influence in attracting and retaining high caliber young women in the Naval Service Of particular interest is the status of women unrestricted line officers (110X), who do not have the opportunity to attain warfare qualifications. This thesis researches the current situation regarding women URL (110X) career development/ patterns, with emphasis on such areas as leadership development, functional areas, Navy requirements and their structure, along with the interaction of these factors. Some predictions concerning career pattern flows, career development viability, and policy implications are also addressed.http://archive.org/details/examinationofunr00mattLieutenant Commander, United States NavyLieutenant, United States NavyApproved for public release; distribution is unlimited

Chemical and Biological Trends during Lake Evolution in Recently Deglaciated Terrain

As newly formed landscapes evolve, physical and biological changes occur that are collectively known as primary succession. Although succession is a fundamental concept in ecology, it is poorly understood in the context of aquatic environments. The prevailing view is that lakes become more enriched in nutrients as they age, leading to increased biological production. Here we report the opposite pattern of lake development, observed from the water chemistry of lakes that formed at various times within the past 10,000 years during glacial retreat at Glacier Bay, Alaska. The lakes have grown more dilute and acidic with time, accumulated dissolved organic carbon and undergone a transient rise in nitrogen concentration, all as a result of successional changes in surrounding vegetation and soils. Similar trends are evident from fossil diatom stratigraphy of lake sediment cores. These results demonstrate a tight hydrologic coupling between terrestrial and aquatic environments during the colonization of newly deglaciated landscapes, and provide a conceptual basis for mechanisms of primary succession in boreal lake ecosystems

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