Maryland and South Carolina have really good women’s basketball teams — two of the four best in the country. But Connecticut and Notre Dame, their respective Final Four opponents on Sunday in Tampa, are a cut above. They’re ranked No. 1 and 2 in the country by the AP, the coaches and the tournament selection committee. They’re the favorites to reach Tuesday’s final in our March Madness predictions and in Vegas. They played each other in last year’s final. And, best of all, they have a rich history — one that isn’t as one-sided as UConn’s recent dominance suggests.Notre Dame has dealt UConn seven of its 18 losses since the start of 2007. In other words, 39 percent of the time UConn has lost in the last eight-plus years, it’s been against Notre Dame.If UConn and Notre Dame play each other in the final, it’d be their 21st meeting since the start of 2007 — the latest ESPN Stats & Info data available. They played 12 regular-season games (11 back when both were in the Big East), plus three Big East conference finals and one semifinal. They’ve also met four times in the last eight Final Fours, with two wins apiece. A Tuesday meeting would be the rubber match.Maryland and South Carolina have been good, but they simply haven’t been as dominant. UConn has won 94.6 percent of its games since the start of 2007, by far the best in the sport. Notre Dame ranks fifth, at 84.1 percent. (Stanford, Green Bay and Baylor are second, third and fourth.) Maryland is 11th, at 80.6 percent. And South Carolina is 53rd, at 64.3 percent. But South Carolina’s and Maryland’s relative inconsistency, coupled with UConn’s and Notre Dame’s late, lamented conference rivalry, means they have a much thinner record against the rest of the Final Four.So let’s look more closely at the UConn-Notre Dame rivalry. UConn has won 13 of their last 20 matchups, or 65 percent. That’s as close as UConn gets these days to a balanced rivalry — it’s the lowest winning percentage UConn has against any team it has played more than five times since the start of 2007. Every team but one that has played UConn at least once in that time has a losing record against the Huskies. (The one exception is longtime rival Tennessee, which won their only recent meeting.) More than 90 percent of UConn opponents haven’t beaten the Huskies even once, including four teams that have played them at least 10 times.Also notable, for a team that has regularly all but clinched its games by halftime, UConn has beaten Notre Dame by an average of less than eight points per game in their 20 meetings. That’s the closest average margin for any UConn opponent that has played the Huskies more than five times since 2007.UConn, meanwhile, is responsible for a big chunk of Notre Dame’s losses since the start of 2007: 13 of 49, or 27 percent. UConn is the only team Notre Dame has played in more than six games in that period that has a winning record against the Fighting Irish.Notre Dame’s recent wins against UConn all came in an astonishingly short spell: The Fighting Irish won seven of eight meetings over a stretch that started with Notre Dame’s upset of UConn in the 2011 Final Four. Notre Dame star Jewell Loyd, a junior and the team’s leading scorer, is the only current player who was a major contributor for the Fighting Irish when they last beat UConn.It’s not the most heated or longstanding rivalry. Before the teams played in December — in a game UConn won by 18 points — espnW’s Graham Hays pointed out that it doesn’t have the rich character and tension of UConn-Tennessee. Notre Dame head coach Muffet McGraw, asked before the game about her relationship with Connecticut coach Geno Auriemma, made it sound like the two were friendly acquaintances in the corporate world. “Geno and I are terrific,” McGraw said. “We saw each other this summer. We’ve got no issues, no problems. Just business as usual for both of us.”If it’s business as usual for both teams on Sunday, we’ll see them renew their acquaintance in the final on Tuesday in Tampa, in the latest edition of the closest thing to a rivalry that Auriemma’s dominant UConn team has these days.
The Murchison meteorite, a carbonaceous chondrite, fell near Murchison in Victoria in Australia in 1969, and is thought to be extremely ancient, possibly even older than the Sun, at 4.65 billion years old. It probably passed through the primordial clouds in the early Solar System, where it would have collected organic compounds. It was retrieved soon after it landed, which meant there was minimal chance of contamination, and it has been studied by scientists hoping the meteorite would yield clues about the possible origins of life on Earth. Leader of the research team, Dr Philippe Schmitt-Kopplin, said the meteorite was like a kind of fossil, and when you try to understand it, you are essentially looking back in time. Dr Schmitt-Kopplin, from the Helmholtz Centre Munich, in Germany, said he was really excited and amazed at the complexity they found. The meteorite has been investigated many times before, but earlier studies used gas chromatography and mass spectrometry and looked for specific compounds such as amino acids. The current study is the first non-targeted examination of the meteorite, and used high resolution technology such as NMR and ultra-high resolution mass spectrometry. The analysis took a few milligrams of crushed rock from the meteorite’s core, and then extracted the organic compounds with solvents.Their approach is based on metabolomics, which Schmitt-Kopplin and his team uses to analyze metabolites in body fluids. The technique attempts to find as many metabolites as possible, and they used the same system on the meteorite. Specifically, the new technique is known as the Fourier transform ion cyclotron resonance/mass spectrometry (FTICR/MS), which enables the scientists to weigh ionized molecules with the accuracy of the mass of an electron.The resolution of the analysis and the number of signals found makes the study record-breaking. Previous investigations were all targeted and used older technologies, and so the diversity was never discovered before. The results of the analysis identified about 14,000 different molecules in the meteorite, which can be combined in millions of different organic compounds. Schmitt-Kopplin said their calculations and interpolation were “very conservative”. Their findings show the nascent Solar System probably had more molecular diversity than present-day Earth.The results of the study appear in the Proceedings of the National Academy of Sciences (PNAS) journal. More information: High molecular diversity of extraterrestrial organic matter in Murchison meteorite revealed 40 years after its fall, Philippe Schmitt-Kopplin et al., PNAS February 16, 2010 vol. 107 no. 7 2763-2768, doi: 10.1073/pnas.0912157107 Murchison meteorite at the The National Museum of Natural History (Washington) © 2010 PhysOrg.com One-of-a-kind meteorite unveiled This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. (PhysOrg.com) — New studies of a meteorite that crashed to Earth four decades ago have found it probably contains millions of organic compounds. The findings shed light on the molecular complexity that existed at or just after the birth of the Solar System. Explore further Citation: Chemical snapshot: Murchison meteorite reveals diversity of early Solar System (2010, February 17) retrieved 18 August 2019 from https://phys.org/news/2010-02-chemical-snapshot-murchison-meteorite-reveals.html
Nanoscale observation of live osteoblasts in culture media, using the SE-ADM system. (A) Representative high-resolution SE-ADM images of osteoblasts cultured with or without osteogenic media for 2 days. Black particles were evident only when cultured in osteogenic media (right, square in the bottom). (B) Representative high-resolution SE-ADM images of osteoblasts cultured with or without osteogenic media for 7 days. There are many black particles when cultured in osteogenic media (right). (C) Representative high-resolution SE-ADM images of the SiN film after cell removal. In normal media, no particles are observed (left). The image of the film after removal of cells cultured in osteogenic media shows many clear black particles dispersed in the whole area (right). (D) Comparison of particle images during 4 to 10 days of culture in osteogenic media. The particle sizes gradually increased. (E) Distribution of particle size measured during 4 to 10 days of culture in osteogenic media. Approximately 900 to 1100 particles per time point were measured and plotted as a histogram. (F) Representative high-resolution SE-ADM images of osteoblasts cultured with osteogenic media for 7 hours. (G) MVBs have clear gray envelopes. (H) Cut images of various MVB sizes, including particles. (I) Comparison of MVBs with or without a gray envelope. (J) Schematic view of intracellular formation and transport of MVB in mineralizing osteoblasts. Scale bars, 1 μm in (A) to (C) and (F); 500 nm in (G); 200 nm in (D, bottom), (H), and (I). Credit: Science Advances, doi: 10.1126/sciadv.aax0672 Mineralization is mediated by osteoblasts, which secrete mineral precursors through matrix vesicles (MVs) as a fundamental process in vertebrates. The vesicles are calcium and phosphate rich, containing organic materials such as acidic proteins. In a new study now published in Science Advances, Tomoaki Iwayama and colleagues at the departments of periodontology, biomedical research, oral science, biomaterials and oral anatomy development used scanning electron-assisted dielectric microscopy (SE-ADM) and super-resolution microscopy (SRM) to assess live osteoblasts during conditions of mineralization at nano-level resolution. They found the calcium-containing vesicles to be multi-vesicular bodies containing mineralizing nanovesicles or matrix vesicles (MVs). According to the observations, the MVs could be transported together with lysosomes and secreted by exocytosis. Iwayama et al. presented proof that the lysosomes could transport amorphous calcium phosphate in mineralizing osteoblast cells. Super-resolution live imaging of calcium containing vesicle transports via lysosomes. (A) Snapshot of time-lapse SRM images of calcein-labeled osteoblasts. Cells were cultured with calcein and stained with Lysotracker and MitoTracker. White arrows indicate colocalization of lysosomes and calcein-positive vesicles. (B) Close-up of time-lapse SRM images of calcein-labeled osteoblasts. Red arrowheads indicate lysosome, and green arrowheads indicate calcein. Once lysosomes fused to calcein-positive vesicles adjacent to mitochondria, they started to move toward extracellular space. (C) Representative SRM image of LAMP1-mCherry–expressing cells. Cells were transfected with LAMP1-mCherry plasmid, cultured with calcein, and stained with MitoTracker. Calcein-positive vesicles matched to LAMP1-mCherry–positive lysosomes. (D) Schematic view of lysosomal involvement in transportation of calcium in mineralizing osteoblasts. Scale bars, 2 μm in (A), 1 μm in (B), and 10 μm in (C). Credit: Science Advances, doi: 10.1126/sciadv.aax0672 Scanning electron-assisted dielectric microscopy (SE-ADM) observation of osteoblasts. (A) High-resolution SE-ADM set up for osteoblast observation. Liquid-sample holder including osteoblasts is mounted on the pre-amplifier-attached stage, which is introduced into the specimen SEM chamber. The scanning electron beam is applied to the W-coated SiN film at a low acceleration voltage. Measurement terminal under the holder detects electrical signals through liquid specimens. Clear intracellular structures are visible (right image). Credit: Science Advances, doi: 10.1126/sciadv.aax0672 Characterization of mineral containing vesicles. (A and B) High-resolution particle images before (A) and after (B) removal of cells cultured in osteogenic media for 7 days. Pseudocolor maps of enlarged particle images indicated by red arrows are shown on the right side of (B). Particles show very smooth structures without crystals. (C) Scanning electron microscopy (SEM) images and EDX spectrometric analysis of particles on a SiN film. SEM image on the left side exhibits the SiN film after removal of cells cultured in normal media, which shows no particles, and EDX spectrometric data show no peaks of phosphorus and calcium. In contrast, the SEM image and EDX spectrometric data on the right side show particles and sharp peaks of phosphorus and calcium after culture in osteogenic media. (D) Analysis of particle elements using EDX spectrometric maps. Particles contained phosphorus, calcium, carbon, and nitrogen. (E) Raman spectra obtained from osteoblasts cultured with or without osteogenic media for 23 days. Sharp peak of 960 cm−1 was evident only in osteogenic media (right side). a.u., arbitrary units. (F) Comparison of SE-ADM images of Alpl knockout (KO) osteoblasts in normal and osteogenic media. Particles completely disappeared in osteogenic media. (G) EDX spectrum of particles from Alpl KO osteoblasts on a SiN film. Left-side EDX spectrometric data exhibit the SiN film after removal of cells cultured in normal media, which show no peaks of phosphorus and calcium. Moreover, particles in osteogenic media of right-side data show no peaks in phosphorus and calcium. Scale bars, 1 μm in (A), (C, top), (D), and (F); 200 nm in (B); 100 nm in (B, right). Credit: Science Advances, doi: 10.1126/sciadv.aax0672 Lysosomal inhibitors block mineralization. (A and C) Confocal live imaging of 50 nM BafA-or 10 μM Vac-1–treated osteoblasts. Cells were cultured in osteogenic media containing BafA or Vac-1 and stained with Hoechst 33342 and LysoTracker Insets show higher magnification and boxed area of each channel. (B and D) SD-ADM images of BafA- or Vac-1–treated osteoblasts. Cells were cultured in osteogenic media containing BafA or Vac-1. (E) Alizain Red S staining performed without fixation. Cells were cultured in osteogenic media containing BafA or Vac-1 and stained with Alizain Red S. Representative confocal images. Scale bars, 50 μm in (A), (C), and (E); 2 μm (B) and (D). Credit: Science Advances, doi: 10.1126/sciadv.aax0672 To overcome these limitations in the present work, Iwayama et al. used a new microscopic system known as scanning electron-assisted dielectric microscopy (SE-ADM). The method had previously achieved nanoscale resolution and high-contrast imaging for mammalian cells in aqueous media without staining. The scientists used the same technique (high resolution SE-ADM) to explore the possibility of viewing MVs in intact osteoblasts to understand biogenesis of MV trafficking. For the osteoblast cell line they used murine (mouse) osteoblastic cell line KUSA-A1, with high osteogenic capacity in vitro and in vivo. After cell culture under adequate conditions, Iwayama et al. observed the cells with SE-ADM to identify normal intracellular structures. The scientists observed MVs to align with collagen fibrils after 4 to 10 days of cell growth in osteogenic media and the secreted particle size increased due to fusion or particle growth, with their sizes consistent with previous reports to suggest they were indeed MVs. This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. Explore further New pathway for cell communication discovered , Bone Citation: Osteoblastic lysosome plays a central role in mineralization (2019, July 11) retrieved 18 August 2019 from https://phys.org/news/2019-07-osteoblastic-lysosome-central-role-mineralization.html Journal information: Science Advances After directly observing the production and secretion of MVs using SE-ADM, the scientists further investigated the involvement of lysosomes in intracellular trafficking of MVs to observe live osteoblast mineralization. They cultured the cells in calcium-containing osteogenic media and stained them with LysoTracker to detect the intracellular components of interest. Iwayama et al. located the calcein-fulfilled vesicles matched with lysosomes to suggest the biogenesis of MVs within lysosomes after their fusion with calcein+ vesicles. The scientists followed the experiments with loss-of-function and functional inhibition studies to further deconstruct the pathways and examine intracellular mechanisms of action during live cell mineralization in vitro. Upon further examination with SE-ADM, they noted the involvement of the lysosomal pathway to transport and secrete intraluminal MVs in a similar process to exosomes. Interestingly, both exosomes and MVs are categorized as extracellular vesicles with similar sizes; they are both secreted by osteoblasts and have shared functions during cell-cell communication. Scientists had previously reported the involvement of mitochondria during mineralization due to the presence of electron-dense calcium and phosphorous-rich granules in osteoblast mitochondria. This was observed with a modified cryotechnique. Furthermore, reports also suggest the direct contact of lysosomes and mitochondria with functional significance. When Iwayama et al. stained cells with LysoTracker together with MitoTracker and observed the intracellular components under N-SIM structured illumination super-resolution microscopy (SRM). They observed the presence of most calcein-fulfilled vesicles next to mitochondria and matched with lysosomes. During SRM-time lapse imaging, the scientists further obtained views of intracellular transport of LysoTracker containing vesicles fused to static calcein vacuoles adjacent to mitochondria to validate their hypothesis. In this way, together with observations of other SRM systems and additional cell lines, Tomoaki Iwayama and colleagues proposed a mineralization mechanism. Wherein lysosomes played a central role in intracellular MV biogenesis and trafficking within osteoblasts. It was reasonable to involve lysosomes for osteoblasts to transport amorphous calcium phosphate without crystallization during its transport in the cytosol. The scientists aim to conduct further experiments to understand the regulatory molecules for MVs and investigate if MVs and exosomes have similar constitutions and mechanism underlying their generation, secretion and function. The SE-ADM strategy used in the present work can be installed into existing scanning electron microscopy apparatus at a low cost. The work developed in the study will offer non-invasive, high-resolution imaging at the nanoscale applicable to all scientific fields. In the next step, Iwayama et al. examined if these particles were MVs containing calcium and/or phosphate. For this, they cultured the cells in osteogenic media for 7 days and observed them using SE-ADM to record very smooth structures without crystal facets. This suggested that the MVs did not crystallize but remained amorphous as also recorded in a previous study. When the scientists examined the MVs on a SiN (silicon mononitride) film, they observed sharp peaks corresponding to phosphorous, calcium, carbon and oxygen elements. They confirmed the findings using Raman spectroscopy to show the presence of calcium phosphate within MVs. The scientists also investigated the effects of hypophosphatasia a medical condition encoded by the Alpl (alkaline phosphatase) gene, wherein osteoblasts do not undergo mineralization in vitro. For this, they edited the genome of osteoblast cells using the CRISPR-Cas9 genome editing technology to generate Alpl knockout osteoblast clones. When Iwayama et al. examined the knockout clones using high-resolution SE-ADM, they did not observe MVs, which was further confirmed using spectrometric analysis due to the absence of phosphorous and calcium peaks. © 2019 Science X Network , Science During the physiological process of bone mineralization, the deposition of calcium phosphate crystals occurs in the extracellular matrix as a fundamental process in all vertebrates. In 1967, biologists Clarke Anderson and Ermanno Bonucci, individually visualized mineral-related particles in the extracellular space using electron microscopy (EM). Scientists later recognized these particles as mineralizing nano-vesicles or matrix vesicles (MVs). During the past 50 years of EM studies on MVs, biologists have grappled to understand the mechanism of MV formation and secretion, which remains largely unknown. Clarifying the mineralizing process of live cells with EM is challenging since sample preparation for EM requires steps on both chemical fixation and alcoholic dehydration. The steps can induce artefacts and even dissolve or remove unstable mineral precursors leaving an organic scaffold known as a “crystal ghost”. While scientists had successfully used the process of EM using fixed and dehydrated tissue to view the structure of mineralized collagen fibrils in bone, to study mineral precursors, they must employ cryo-EM processes to avoid dehydration and facilitate costly, extremely fast cooling with small specimens. More information: Tomoaki Iwayama et al. Osteoblastic lysosome plays a central role in mineralization, Science Advances (2019). DOI: 10.1126/sciadv.aax0672 N. Reznikov et al. A materials science vision of extracellular matrix mineralization, Nature Reviews Materials (2016). DOI: 10.1038/natrevmats.2016.41 Natalie Reznikov et al. Fractal-like hierarchical organization of bone begins at the nanoscale, Science (2018). DOI: 10.1126/science.aao2189 Irving M. Shapiro et al. Matrix vesicles: Are they anchored exosomes?, Bone (2015). DOI: 10.1016/j.bone.2015.05.013