Plasma Soluble Human Elastin Fragments as an Intra-Aneurysmal Localized Biomarker for Ruptured Intracranial Aneurysm

Background—Fragmentation of the tunica media is a hallmark of intracranial aneurysm formation, often leading to aneurysmal progression and subsequent rupture. The objective of this study is to determine the plasma level of elastin fragments in the lumen of ruptured versus unruptured human intracranial aneurysms. Methods and Results—One hundred consecutive patients with/without ruptured saccular intracranial aneurysms undergoing endovascular coiling or stent-assisted coiling were recruited. Blood samples were collected from the lumen of intracranial aneurysm using a microcatheter. The tip of the microcatheter was placed inside the aneurysm’s sac in close proximity to the inner wall of the dome. Plasma levels of elastin fragments were measured using an ELISA-based method. Mean plasma level of soluble human elastin fragments was significantly greater in ruptured aneurysms when compared with nonruptured aneurysms (102.0±15.5 versus 39.3±9.6 ng/mL; P\u3c0.001). Mean plasma level of soluble human elastin fragments did not have significant correlation with age, sex, size, or aneurysm location. Conclusions—The present study revealed that a significantly higher concentration of soluble human elastin fragments in the lumen of ruptured intracranial aneurysms when compared with nonruptured ones. © 2018 The Authors

Stratigraphic Architecture of Bedrock Reference Section, Victoria Crater, Meridiani Planum, Mars

The Mars Exploration Rover Opportunity has investigated bedrock outcrops exposed in several craters at Meridiani Planum, Mars, in an effort to better understand the role of surface processes in its geologic history. Opportunity has recently completed its observations of Victoria crater, which is 750 m in diameter and exposes cliffs up to ∼15 m high. The plains surrounding Victoria crater are ∼10 m higher in elevation than those surrounding the previously explored Endurance crater, indicating that the Victoria crater exposes a stratigraphically higher section than does the Endurance crater; however, Victoria strata overlap in elevation with the rocks exposed at the Erebus crater. Victoria crater has a well-developed geomorphic pattern of promontories and embayments that define the crater wall and that reveal thick bedsets (3–7 m) of large-scale cross-bedding, interpreted as fossil eolian dunes. Opportunity was able to drive into the crater at Duck Bay, located on the western margin of Victoria crater. Data from the Microscopic Imager and Panoramic Camera reveal details about the structures, textures, and depositional and diagenetic events that influenced the Victoria bedrock. A lithostratigraphic subdivision of bedrock units was enabled by the presence of a light-toned band that lines much of the upper rim of the crater. In ascending order, three stratigraphic units are named Lyell, Smith, and Steno; Smith is the light-toned band. In the Reference Section exposed along the ingress path at Duck Bay, Smith is interpreted to represent a zone of diagenetic recrystallization; however, its upper contact also coincides with a primary erosional surface. Elsewhere in the crater the diagenetic band crosscuts the physical stratigraphy. Correlation with strata present at nearby promontory Cape Verde indicates that there is an erosional surface at the base of the cliff face that corresponds to the erosional contact below Steno. The erosional contact at the base of Cape Verde lies at a lower elevation, but within the same plane as the contact below Steno, which indicates that the material above the erosional contact was built on significant depositional paleotopography. The eolian dune forms exposed in Duck Bay and Cape Verde, combined with the geometry of the erosional surface, indicate that these outcrops may be part of a larger-scale draa architecture. This insight is possible only as a result of the larger-scale exposures at Victoria crater, which significantly exceed the more limited exposures at the Erebus, Endurance, and Eagle craters

Multi-strategy engineering greatly enhances provitamin A carotenoid accumulation and stability in Arabidopsis seeds

Staple grains with low levels of provitamin A carotenoids contribute to the global prevalence of vitamin A deficiency and therefore are the main targets for provitamin A biofortification. However, carotenoid stability during both seed maturation and postharvest storage is a serious concern for the full benefits of carotenoid biofortified grains. In this study, we utilized Arabidopsis as a model to establish carotenoid biofortification strategies in seeds. We discovered that manipulation of carotenoid biosynthetic activity by seed-specific expression of Phytoene synthase (PSY) increases both provitamin A and total carotenoid levels but the increased carotenoids are prone to degradation during seed maturation and storage, consistent with previous studies of provitamin A biofortified grains. In contrast, stacking with Orange (ORHis), a gene that initiates chromoplast biogenesis, dramatically enhances provitamin A and total carotenoid content and stability. Up to 65- and 10-fold increases of β-carotene and total carotenoids, respectively, with provitamin A carotenoids composing over 63% were observed in the seeds containing ORHis and PSY. Co-expression of Homogentisate geranylgeranyl transferase (HGGT) with ORHis and PSY further increases carotenoid accumulation and stability during seed maturation and storage. Moreover, knocking-out of β-carotene hydroxylase 2 (BCH2) by CRISPR/Cas9 not only potentially facilitates β-carotene accumulation but also minimizes the negative effect of carotenoid over production on seed germination. Our findings provide new insights into various processes on carotenoid accumulation and stability in seeds and establish a multiplexed strategy to simultaneously target carotenoid biosynthesis, turnover, and stable storage for carotenoid biofortification in crop seeds

Regional Structural Orientation of the Mount Sharp Group Revealed by In Situ Dip Measurements and Stratigraphic Correlations on the Vera Rubin Ridge

Ground‐based bedding orientation measurements are critical to determine the geologic history and processes of sedimentation in Gale crater, Mars. We constrain the dip of lacustrine strata of the Blunts Point, Pettegrove Point, and Jura members of the Murray formation using a combination of regional stratigraphic correlations and bed attitude measurements from stereo Mastcam images taken by the Mars Science Laboratory Curiosity rover. In situ bed attitude measurements using a principal component analysis‐based regression method reveal a wide range of dips and dip azimuths owing to a combination of high stereo errors, postdepositional deformation of strata (e.g., fracturing, rotation, and impact cratering), and different primary depositional dips. These constrain regional dips to be within several degrees of horizontal on average. Stratigraphic correlations between targets observed in the Glen Torridon trough and at the Pettegrove Point‐Jura member contact of Vera Rubin ridge (VRR) constrain dips to be between 3°SE and 2°NW, consistent with nearly flat strata deposited horizontally on an equipotential surface. The Jura member is determined to be stratigraphically equivalent to the northern portion of the Glen Torridon trough. Rover‐based dip magnitudes are generally significantly shallower than the orientation of VRR member contacts measured from High Resolution Imaging Science Experiment‐based traces, suggesting the sedimentary strata and VRR member contacts may be discordant

The Holy Grail: A road map for unlocking the climate record stored within Mars' polar layered deposits

In its polar layered deposits (PLD), Mars possesses a record of its recent climate, analogous to terrestrial ice sheets containing climate records on Earth. Each PLD is greater than 2 ​km thick and contains thousands of layers, each containing information on the climatic and atmospheric state during its deposition, creating a climate archive. With detailed measurements of layer composition, it may be possible to extract age, accumulation rates, atmospheric conditions, and surface activity at the time of deposition, among other important parameters; gaining the information would allow us to “read” the climate record. Because Mars has fewer complicating factors than Earth (e.g. oceans, biology, and human-modified climate), the planet offers a unique opportunity to study the history of a terrestrial planet’s climate, which in turn can teach us about our own planet and the thousands of terrestrial exoplanets waiting to be discovered. During a two-part workshop, the Keck Institute for Space Studies (KISS) hosted 38 Mars scientists and engineers who focused on determining the measurements needed to extract the climate record contained in the PLD. The group converged on four fundamental questions that must be answered with the goal of interpreting the climate record and finding its history based on the climate drivers. The group then proposed numerous measurements in order to answer these questions and detailed a sequence of missions and architecture to complete the measurements. In all, several missions are required, including an orbiter that can characterize the present climate and volatile reservoirs; a static reconnaissance lander capable of characterizing near surface atmospheric processes, annual accumulation, surface properties, and layer formation mechanism in the upper 50 ​cm of the PLD; a network of SmallSat landers focused on meteorology for ground truth of the low-altitude orbiter data; and finally, a second landed platform to access ~500 ​m of layers to measure layer variability through time. This mission architecture, with two landers, would meet the science goals and is designed to save costs compared to a single very capable landed mission. The rationale for this plan is presented below. In this paper we discuss numerous aspects, including our motivation, background of polar science, the climate science that drives polar layer formation, modeling of the atmosphere and climate to create hypotheses for what the layers mean, and terrestrial analogs to climatological studies. Finally, we present a list of measurements and missions required to answer the four major questions and read the climate record. 1. What are present and past fluxes of volatiles, dust, and other materials into and out of the polar regions? 2. How do orbital forcing and exchange with other reservoirs affect those fluxes? 3. What chemical and physical processes form and modify layers? 4. What is the timespan, completeness, and temporal resolution of the climate history recorded in the PLD

Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

Convergence of a common solution to broad ebolavirus neutralization by glycan cap directed human antibodies

Antibodies that target the glycan cap epitope on ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization is not well-understood. Here we present cryo-electron microscopy (cryo-EM) structures of several glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLD) to the glycan cap, which we name the MLD-anchor and cradle. Antibodies that bind to the MLD-cradle share common features, including the use of IGHV1-69 and IGHJ6 germline genes, which exploit hydrophobic residues and form beta-hairpin structures to mimic the MLD-anchor, disrupt MLD attachment, destabilize GP quaternary structure and block cleavage events required for receptor binding. Our results collectively provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies