Minocycline reduces microgliosis and improves subcortical white matter function in a model of cerebral vascular disease

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Chronic cerebral hypoperfusion is a key mechanism associated with white matter disruption in cerebral vascular disease and dementia. In a mouse model relevant to studying cerebral vascular disease, we have previously shown that cerebral hypoperfusion disrupts axon-glial integrity and the distribution of key paranodal and internodal proteins in subcortical myelinated axons. This disruption of myelinated axons is accompanied by increased microglia and cognitive decline. The aim of the present study was to investigate whether hypoperfusion impairs the functional integrity of white matter, its relation with axon-glial integrity and microglial number, and whether by targeting microglia these effects can be improved. We show that in response to increasing durations of hypoperfusion, the conduction velocity of myelinated fibres in the corpus callosum is progressively reduced and that paranodal and internodal axon-glial integrity is disrupted. The number of microglial cells increases in response to hypoperfusion and correlates with disrupted paranodal and internodal integrity and reduced conduction velocities. Further minocycline, a proposed anti-inflammatory and microglia inhibitor, restores white matter function related to a reduction in the number of microglia. The study suggests that microglial activation contributes to the structural and functional alterations of myelinated axons induced by cerebral hypoperfusion and that dampening microglia numbers/proliferation should be further investigated as potential therapeutic benefit in cerebral vascular disease.We gratefully acknowledge the support of Alzheimer's Research UK (ARUK) in funding this project and for providing a small grant via the ARUK Scotland Network Centre. SS is funded by an ARUK PhD studentship. Funding support from the Alzheimer's Society is also gratefully acknowledged. BMcC was funded by grants from the BBSRC and MRC. We would also like to acknowledge Abcam for the supply of TMEM119 antibody and technical support

TOI-1338 : TESS' first transiting circumbinary planet

Funding: Funding for the DPAC has been provided by national institutions, in particular, the institutions participating in the Gaia Multilateral Agreement. W.F.W. and J.A.O.thank John Hood Jr. for his generous support of exoplanet research at SDSU. Support was also provided and acknowledged through NASA Habitable Worlds grant 80NSSC17K0741 and NASA XRP grant 80NSSC18K0519. This work is partly supported by NASA Habitable Worlds grant 80NSSC17K0741. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under grant No.(DGE-1746045). A.H.M.J.T. has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 803193/BEBOP) and from a Leverhulme Trust Research Project grant No. RPG-2018-418. A.C. acknowledges support by CFisUC strategic project (UID/FIS/04564/2019).We report the detection of the first circumbinary planet (CBP) found by Transiting Exoplanet Survey Satellite (TESS). The target, a known eclipsing binary, was observed in sectors 1 through 12 at 30 minute cadence and in sectors 4 through 12 at 2 minute cadence. It consists of two stars with masses of 1.1 M⊙ and 0.3 M⊙ on a slightly eccentric (0.16), 14.6 day orbit, producing prominent primary eclipses and shallow secondary eclipses. The planet has a radius of ∼6.9 R⊕ and was observed to make three transits across the primary star of roughly equal depths (∼0.2%) but different durations—a common signature of transiting CBPs. Its orbit is nearly circular (e ≍ 0.09) with an orbital period of 95.2 days. The orbital planes of the binary and the planet are aligned to within ∼1°. To obtain a complete solution for the system, we combined the TESS photometry with existing ground-based radial-velocity observations in a numerical photometric-dynamical model. The system demonstrates the discovery potential of TESS for CBPs and provides further understanding of the formation and evolution of planets orbiting close binary stars.Publisher PDFPeer reviewe

The interplay between mineral metabolism, vascular calcification and inflammation in Chronic Kidney Disease (CKD): challenging old concepts with new facts

Chronic kidney disease (CKD) is one of the most powerful predictors of premature cardiovascular disease (CVD), with heightened susceptibility to vascular intimal and medial calcification associated with a high cardiovascular mortality. Abnormal mineral metabolism of calcium (Ca) and phosphate (P) and underlying (dys)regulated hormonal control in CKD-mineral and bone disorder (MBD) is often accompanied by bone loss and increased vascular calcification (VC). While VC is known to be a multifactorial process and a major risk factor for CVD, the view of primary triggers and molecular mechanisms complexity has been shifting with novel scientific knowledge over the last years. In this review we highlight the importance of calcium-phosphate (CaP) mineral crystals in VC with an integrated view over the complexity of CKD, while discuss past and recent literature aiming to highlight novel horizons on this major health burden. Exacerbated VC in CKD patients might result from several interconnected mechanisms involving abnormal mineral metabolism, dysregulation of endogenous calcification inhibitors and inflammatory pathways, which function in a feedback loop driving disease progression and cardiovascular outcomes. We propose that novel approaches targeting simultaneously VC and inflammation might represent valuable new prognostic tools and targets for therapeutics and management of cardiovascular risk in the CKD population.Portuguese Foundation for Science and Technology (UID/Multi/04326/2019); Portuguese Society of Nephrology (SPN)info:eu-repo/semantics/publishedVersio

Tracking the Australian plate motion through the Cenozoic: Constraints from 40Ar/39Ar geochronology

Here we use geochronology of Australian intraplate volcanoes to construct a high-resolution plate-velocity record and to explore how tectonic events in the southwest Pacific may have influenced plate motion. Nine samples from five volcanoes yield ages from 33.6 ± 0.5 to 27.3 ± 0.4 Ma and, when combined with published ages from 30 to 16 Ma, show that the rate of volcanic migration was not constant. Instead, the results indicate distinct changes in Australian plate motion. Fast northward velocities (61 ± 8 and 57 ± 4 km/Ma) prevailed from 34 to 30 (±0.5) and from 23 to 16 (±0.5) Ma, respectively, with distinct reductions to 20 ± 10 and 22 ± 5 km/Ma from 30 to 29 (±0.5) Ma and from 26 to 23 (±0.5) Ma. These velocity reductions are concurrent with tectonic collisions in New Guinea and Ontong Java, respectively. Interspersed between the periods of sluggish motion is a brief 29-26 (±0.5) Ma burst of atypically fast northward plate movement of 100 ± 20 km/Ma. We evaluate potential mechanisms for this atypically fast velocity, including catastrophic slab penetration into the lower mantle, thermomechanical erosion of the lithosphere, and plume-push forces; none are appropriate. This period of fast motion was, however, coincident with a major southward propagating slab tear that developed along the northeastern plate margin, following partial jamming of subduction and ophiolite obduction in New Caledonia. Although it is unclear whether such an event can play a role in driving fast plate motion, numerical or analogue models may help address this question. Key Points We determine nine 40Ar/39Ar ages from five Cenozoic volcanoes in Australia Slow velocities correlate with New Guinea and Ontong Java collisions Anomalously fast velocity of 100 +/- 20 km/Ma is identified from 29-26 M

Social Structure and Reactions in the Slave Community: Evidence from New Sources

Evening Sessio

Eagle Assist - Chatbot for Georgia Southern University

Eagle Assist is a virtual customer service representative designed to help users gain information about Georgia Southern University. The chatbot will have information ranging from Student Life to Academics and will respond to questions by pulling from both static pre-made answers and dynamically made answers via web scraping

A pipeline for rapidly incorporating real objects into a mixed environment

A method is presented to rapidly incorporate real objects into virtual environments using laser scanned 3D models with color-based marker tracking. Both the real objects and their geometric models are put into a Mixed Environment (ME). In the ME, users can manipulate the scanned, articulated real objects, such as tools, parts, and physical correlates to complex computer-aided design (CAD) models. Our aim is to allow engineering teams to effectively conduct hands-on assembly design verification. This task would be simulated at a high degree of fidelity, and would benefit from the natural interaction afforded by a ME with many specific real objects. 1