Rodney Kizito from U.S. Department of Energy discusses solar energy, mathematics, and microgrids. When you flip a switch to turn on a light, where does that energy come from? In a traditional power grid, electricity is generated at large power plants and then transmitted long distances. But now, individual homes and businesses with solar panels can generate some or all of their own power and even send energy into the rest of the grid. Modifying the grid so that power can flow in both directions depends on mathematics. With linear programming and operations research, engineers design efficient and reliable systems that account for constraints like the electricity demand at each location, the costs of solar installation and distribution, and the energy produced under different weather conditions. Similar mathematics helps create "microgrids" — small, local systems that can operate independent of the main grid.

Systemic antibody light chains (AL) amyloidosis is characterized by deposition of amyloid fibrils derived from a particular antibody light chain. Cardiac involvement is a major risk factor for mortality. Using MAS solid-state NMR, we studied the fibril structure of a recombinant light chain fragment corresponding to the fibril protein from patient FOR005, together with fibrils formed by protein sequence variants that are derived from the closest germline (GL) sequence. Both analyzed fibril structures were seeded with ex-vivo amyloid fibrils purified from the explanted heart of this patient. We find that residues 11-42 and 69-102 adopt β-sheet conformation in patient protein fibrils. We identify arginine-49 as a key residue that forms a salt bridge to aspartate-25 in the patient protein fibril structure. In the germline sequence, this residue is replaced by a glycine. Fibrils from the GL protein and from the patient protein harboring the single point mutation R49G can be both heterologously seeded using patient ex-vivo fibrils. Seeded R49G fibrils show an increased heterogeneity in the C-terminal residues 80-102, which is reflected by the disappearance of all resonances of these residues. By contrast, residues 11-42 and 69-77, which are visible in the MAS solid-state NMR spectra, show 13Cα chemical shifts that are highly like patient fibrils. The mutation R49G thus induces a conformational heterogeneity at the C terminus in the fibril state, whereas the overall fibril topology is retained. These findings imply that patient mutations in FOR005 can stabilize the fibril structure.

Jessica Y. Franco
Dec 1, 2020; 19:1936-1951
Research

Alison B. Ross
Nov 30, 2020; 0:R120.002190v1-mcp.R120.002190
Review

Amyloid fibrils are polymeric structures originating from aggregation of misfolded proteins. In vivo, proteolysis may modulate amyloidogenesis and fibril stability. In light chain (AL) amyloidosis, fragmented light chains (LCs) are abundant components of amyloid deposits; however, site and timing of proteolysis are debated. Identification of the N and C termini of LC fragments is instrumental to understanding involved processes and enzymes. We investigated the N and C terminome of the LC proteoforms in fibrils extracted from the hearts of two AL cardiomyopathy patients, using a proteomic approach based on derivatization of N- and C-terminal residues, followed by mapping of fragmentation sites on the structures of native and fibrillar relevant LCs. We provide the first high-specificity map of proteolytic cleavages in natural AL amyloid. Proteolysis occurs both on the LC variable and constant domains, generating a complex fragmentation pattern. The structural analysis indicates extensive remodeling by multiple proteases, largely taking place on poorly folded regions of the fibril surfaces. This study adds novel important knowledge on amyloid LC processing: although our data do not exclude that proteolysis of native LC dimers may destabilize their structure and favor fibril formation, the data show that LC deposition largely precedes the proteolytic events documentable in mature AL fibrils.

Vitamin A aldehyde covalently bound to opsin protein is embedded in a phospholipid-rich membrane that supports photon absorption and phototransduction in photoreceptor cell outer segments. Following absorption of a photon, the 11-cis-retinal chromophore of visual pigment in photoreceptor cells isomerizes to all-trans-retinal. To maintain photosensitivity 11-cis-retinal must be replaced. At the same time, however, all-trans-retinal has to be handled so as to prevent nonspecific aldehyde activity. Some molecules of retinaldehyde upon release from opsin are efficiently reduced to retinol. Other molecules are released into the lipid phase of the disc membrane where they form a conjugate (N-retinylidene-PE, NRPE) through a Schiff base linkage with phosphatidylethanolamine (PE). The reversible formation of NRPE serves as a transient sink for retinaldehyde that is intended to return retinaldehyde to the visual cycle. However, if instead of hydrolyzing to PE and retinaldehyde, NRPE reacts with a second molecule of retinaldehyde a synthetic pathway is initiated that leads to the formation of multiple species of unwanted bisretinoid fluorophores. We report on recently identified members of the bisretinoid family some of which differ with respect to the acyl chains associated with the glycerol backbone. We discuss processing of the lipid moieties of these fluorophores in lysosomes of retinal pigment epithelial (RPE) cells, their fluorescence characters and new findings related to light and iron-associated oxidation of bisretinoids.

Small admixtures in water, e.g. of metal ions, often act as cell growth regulators. Here we report that enrichment of deuterium content in water, normally found at 8 mm concentration, two-three folds increases cell proliferation and lowers the oxidative stress level as well. Acting as an anti-oxidant, deuterium-enriched water prevents the toxic effect of such oxidative agents as hydrogen peroxide and auranofin. This action is opposite to that of deuterium depletion that is known to suppress cell growth and induce oxidative stress in mitochondria. We thus hypothesize that deuterium may be a natural cell growth regulator that controls mitochondrial oxidation-reduction balance. Because growth acceleration is reduced approximately by half by addition to water a minute amount (0.15%) of ¹⁸O isotope, at least part of the deuterium effect on cell growth can be explained by the isotopic resonance phenomenon. A slight (2-fold) enrichment of deuterium in water accelerates human cell growth. Quantitative MS based proteomics determined changes in protein abundances and redox states and found that deuterium-enriched water acts mainly through decreasing ROS production in mitochondria. This action is opposite to that of deuterium depletion that suppresses cell growth by inducing oxidative stress. Thus deuterium may be a natural cell growth regulator that controls mitochondrial oxidation-reduction balance. The role of isotopic resonance in this effect was validated by further experiments on bacteria.

Huanglongbing (HLB) is the most devastating and widespread citrus disease. All commercial citrus varieties are susceptible to the HLB-associated bacterium, Candidatus Liberibacter asiaticus (CLas), which resides in the phloem. The phloem is part of the plant vascular system and is involved in sugar transport. To investigate the plant response to CLas, we enriched for proteins surrounding the phloem in an HLB susceptible sweet orange variety, Washington navel (Citrus sinensis (L) Osbeck). Quantitative proteomics revealed global changes in the citrus proteome after CLas inoculation. Plant metabolism and translation were suppressed, whereas defense-related proteins such as peroxidases, proteases and protease inhibitors were induced in the vasculature. Transcript accumulation and enzymatic activity of plant peroxidases in CLas infected sweet orange varieties under greenhouse and field conditions were assessed. Although peroxidase transcript accumulation was induced in CLas infected sweet orange varieties, peroxidase enzymatic activity varied. Specific serine proteases were up-regulated in Washington navel in the presence of CLas based on quantitative proteomics. Subsequent activity-based protein profiling revealed increased activity of two serine proteases, and reduced activity of one protease in two C. sinensis sweet orange varieties under greenhouse and field conditions. The observations in the current study highlight global reprogramming of the citrus vascular proteome and differential regulation of enzyme classes in response to CLas infection. These results open an avenue for further investigation of diverse responses to HLB across different environmental conditions and citrus genotypes.

In all cells, proteins are continuously synthesized and degraded in order to maintain protein homeostasis and modify gene expression levels in response to stimuli. Collectively, the processes of protein synthesis and degradation are referred to as protein turnover. At steady state, protein turnover is constant to maintain protein homeostasis, but in dynamic responses, proteins change their rates of synthesis and degradation in order to adjust their proteomes to internal or external stimuli. Thus, probing the kinetics and dynamics of protein turnover lends insight into how cells regulate essential processes such as growth, differentiation, and stress response. Here we outline historical and current approaches to measuring the kinetics of protein turnover on a proteome-wide scale in both steady-state and dynamic systems, with an emphasis on metabolic tracing using stable-isotope-labeled amino acids. We highlight important considerations for designing proteome turnover experiments, key biological findings regarding the conserved principles of proteome turnover regulation, and future perspectives for both technological and biological investigation.

A Qantas airlines flight made an emergency landing at Sydney Airport on Friday afternoon after suffering engine failure shortly after takeoff, the company said.

A flight of Florida-based Spirit Airlines was hit by gunfire while attempting to land in Haiti with a crew member that sustained "minor injuries."

Oct. 31, 2024 — Giga Computing, a subsidiary of GIGABYTE and a leader in generative AI servers and advanced cooling technologies, will participate in today’s AI Accelerator Skyscraper Congress, hosted […]

The post GIGABYTE Joins AI Accelerator Skyscraper Congress to Highlight Sustainable Supercomputing Advances appeared first on HPCwire.

The Globus user conference, now in its 22nd year, brought together over 180 researchers, system administrators, developers, and IT leaders from 55 top research computing centers, national labs, federal agencies, […]

The post Highlights from GlobusWorld 2024: The Conference for Reimagining Research IT appeared first on HPCwire.

The data fabric has emerged as an enterprise data management pattern for companies that struggle to provide large teams of users with access to well-managed, integrated, and secured data. Now […]

The post NSF-Funded Data Fabric Takes Flight appeared first on HPCwire.

The U.S. Navy conducted a two-missile test flight of unarmed life-extended Trident II-D5LE missiles from the USS Wyoming in the Eastern Test Range off the coast of Cape Canaveral, Fla, the Navy announced.

ATLANTA, Nov. 7, 2024 — As the high-performance computing (HPC) community gathers in Atlanta for SC24, the world’s largest HPC conference, the event will feature presentations from thought leaders and […]

The post SC24 Invited Talks to Spotlight HPC’s Role in AI, Quantum Computing, and Sustainability appeared first on HPCwire.

ATLANTA, Nov. 12, 2024 — Sylabs, in collaboration with Sandia National Laboratories, will host a Birds of a Feather (BoF) session at SC24 titled Integrating Confidential Computing into High-Performance Cloud Workflows. […]

The post Sylabs Highlights Confidential Computing in HPC at SC24 BoF Session appeared first on HPCwire.

TEL AVIV, Israel, Nov. 12, 2024 — LightSolver today announced that it will be exhibiting and presenting at SC24, the international conference for high-performance computing (HPC), networking, storage, and analysis […]

The post LightSolver Highlights Laser Computing Advancements for HPC at SC24 appeared first on HPCwire.

The Federal Aviation Administration has banned flights to-and-from Haiti for at least 30 days after JetBlue and Spirit Airlines planes were hit by gunfire Monday during attempts to land in Port-au-Prince.

A study reveals the hidden dangers of night time light pollution for brain health.

Oprah.com http://www.oprah.com/shiftyourlife/strategies-for-getting-unstuck/all Harvard Business Review How Perfectionists Can Get Out of Their Own Way GOOD Magazine Full article archive Mind Body Green 3 Tips To Stop Taking Criticism So Personally  

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Massachusetts is the fifth state to join the Innovative Assessment Demonstration Authority created through the Every Student Succeeds Act, which allows states to experiment with new forms of testing.

U.S. Ed Secretary DeVos has approved plans for 46 states, plus the District of Columbia and Puerto Rico. Still waiting: California, Florida, Oklahoma, and Utah.

U.S. Ed Secretary DeVos has approved plans for 46 states, plus the District of Columbia and Puerto Rico. Still waiting: California, Florida, Oklahoma, and Utah.

Alabama lawmakers passed a charter school law last year, becoming the 43rd state to adopt one.

Education Secretary Betsy DeVos has finally OK'd Florida's plan to implement the Every Student Succeeds Act. That means that single state, plus Puerto Rico and the District of Columbia, has gotten the go-ahead for its plan.

It's Oregon women's basketball vs. Baylor in a marquee nonconference college basketball matchup. Follow for live score updates, game highlights.

Dazzling first with a relentless hawking defense that helped force 22 turnovers, then adding an almost frantic-paced offensive assault, the 2-0 No. 6-ranked Irish overwhelmed Purdue (1-1), 102-58, at Mackey Arena in West Lafayette, Ind. Dynamo guard Hannah Hidalgo was slapping, diving and picking pockets all night, making life miserable for any Boilermaker stuck bringing the ball up the floor. ► Snap Counts: Here's who played for Notre Dame football against Florida St.

A new exhibition co-presented by the National Portrait Gallery and the Archives of American Art explores the seminal artist’s work

Berlin- FAO Director-General José Graziano da Silva has highlighted some of the most important events on the organization’s 2015 calendar during meetings with agriculture ministers who attended the Global Forum [...]

FAO, IFAD and WFP have launched a brand new Rome-based agencies (RBA) website. The RBAs share a common vision, guiding principles for enhanced collaboration and distinctive strengths that build [...]

To keep up to date on FAO’s most recent publications, sign up to the monthly newsletter produced by the Publications team of the Office of Communications, which provides a [...]

To keep up to date on FAO’s most recent publications, sign up to the monthly newsletter produced by the Publications team of the Office of Communications, which [...]

To keep up to date on FAO’s most recent publications, sign up to the monthly newsletter produced by the Publications team of the Office of Communications, which [...]

To keep up to date on FAO’s most recent publications, sign up to the monthly newsletter produced by the Publications team of the Office of [...]

To keep up to date on FAO’s most recent publications, sign up to the monthly newsletter produced by the Publications team of the Office of Communications, [...]

The FAO monthly publications newsletter produced by the Publications team of the Office of Communications is now also available in French. Sign up to receive updates on publications available in French [...]

The answer depends on how you feel about cluster headaches

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Five categories (People, Arts, Nature, Travel and Mobile) and a grand prize of $2,000.

Astrophysicist Stephen Murray explains how X-ray energies can be used to understand dark matter and its place in the universe

The Sloan Digital Sky Survey recently released the largest ever 3-D map of the sky with some 540,000 galaxies

Boston’s iconic lighthouse, the Boston Light, is managed by a single person: Sally Snowman. She is the 70th keeper of the lighthouse since it was built over 300 years ago.

Five categories (People, Arts, Nature, Travel and Mobile) and a grand prize of $2,000.

For decades, in a tradition imported from Belgium, bowlers in Michigan have rolled their balls at feathers, not pins (Edited and produced by: Roberta Cruger)

When Gary Roberts found this orphaned elephant next to its dead mother, he made an attempt to fly it to safety

Unearthed last year, the remains could reveal new information on the extinct sea reptile, which crushed mollusks and shelled creatures with its large, round teeth

Orbiting Barnard's star, the nearest solo star to Earth, the world is too hot to be habitable—a scorching 257 degrees Fahrenheit