ural Portuguese FM warns of EU’s ‘cultural tendency’ to overregulate By biztoc.com Published On :: Wed, 13 Nov 2024 06:19:08 GMT Portuguese Foreign Minister Paulo Rangel warned on Tuesday of the downside of Europe's "cultural tendency" to "over-regulate" and called for a better "balance" between technological development and the defence of democracy and human rights. Read more. "Europe has a cultural tendency to… Full Article
ural Do Natural Organic Positions and AdWord Postions Work Interactively? By linkworxseo.wordpress.com Published On :: Mon, 07 Jan 2013 02:20:01 +0000 How Organic Placement is Affected Some people seem to be hell-bent on believing that it matters. There is no problem with believing it does have a direct effect on organic placement, but the fact of the matter is; it does not. Although you are entitled to believe what you want to believe, but knowing whether […] Full Article LINK BUILDING PAY PER CLICK (PPC) adwords natural natural-organic-placement organic organic-positions pay-per-click ppc
ural The Outdoors - A Natural Place for Young People with Autism, End of Project Report By lx.iriss.org.uk Published On :: Wednesday, December 13, 2017 - 10:02 This End of Project Report describes an innovative Transition to Work Programme for young people with autistic spectrum diagnoses and is the result of a pilot programme developed by Lothian Autistic Society (LAS) and Scottish Outdoor Education Centres (SOEC) and made possible through funding from Scottish Natural Heritage (SNH). The pilot had the twin aims of developing employability skills and exploring the therapeutic value of the outdoors. Full Article
ural Natural Disasters Aren’t Gender Neutral – Hurricanes Milton and Helene Prove It By feminist.org Published On :: Thu, 24 Oct 2024 16:18:20 +0000 Photo by NASA Natural disasters don’t just ravage landscapes—they also expose and deepen systemic inequalities. Recent hurricanes, Milton and Helene, tore through Florida, Georgia, and the Carolinas, destroying homes, businesses, and the lives built across generations. While governments rush to repair infrastructure and restore housing, they often overlook the people most impacted in the long term—especially […] The post Natural Disasters Aren’t Gender Neutral – Hurricanes Milton and Helene Prove It appeared first on Feminist Majority Foundation. No related posts. Full Article Climate Change climate change hurricanes news
ural A natural personal care brand that gives back to communities By inhabitat.com Published On :: Mon, 10 Jul 2023 16:30:00 +0000 Soapbox is a company dedicated to providing meticulously-crafted personal care products that focus on the health of humans and the environment. [...] Full Article shower soap personal care products shampoo bath products Personal Care
ural Explore the natural beauty of Norway by treetop walkway By inhabitat.com Published On :: Wed, 19 Jul 2023 16:30:00 +0000 A new elevated wooden boardwalk in Fyresdal, Norway invites visitors to embrace a simultaneous expression of exceptional design and environmental sustainability. Traversing the natural landscape, the six-feet wide boardwalk gracefully snakes from the forest floor, skirting the picturesque Lake Fyresvatn. It ascends amidst the lofty treetops, culminating at the majestic summit of Klokkarhamaren, all while protecting the environment against unnecessary harm. [...] Full Article Landscape Architecture norway treetop boardwalk walkway
ural Environmental education is imbedded in this cultural center By inhabitat.com Published On :: Fri, 04 Aug 2023 15:30:00 +0000 Sometimes architecture is about much more than the materials and design of a building. This is the case for Pabellón Centro de Cultura Ambiental (CCA), a facility with the goal of increasing society's environmental awareness. Designed by Taller de Arquitectura, CCA stands as a model for urban planning that incorporates culture, history, economy and the needs of both the community and the environment. [...] Full Article mexico Community Education cultural center post-format-gallery Public Spaces
ural The first agricultural community of its kind in Ontario By inhabitat.com Published On :: Thu, 10 Aug 2023 16:30:00 +0000 Humans living in harmony with nature and with each other is really the goal of sustainable, environmentally-friendly design. And it is hardly a hip and modern idea, not unless you think the Stone Age is trendy. Long ago, people banded together in groups to live and work together as one community, rather than as individuals. Now, Castlepoint Numa is bringing this ancient idea into the modern era with an innovative design.[...] Full Article Landscape Architecture canada community agriculture post-format-gallery agricultural community
ural A Journey of a Swiss Traveller by Train to the Urals By englishrussia.com Published On :: Tue, 01 Feb 2022 14:20:17 +0000 The post A Journey of a Swiss Traveller by Train to the Urals appeared first on English Russia. Full Article Culture History ural
ural Rare Natural Phenomenon Observed in Saint Petersburg By englishrussia.com Published On :: Sat, 02 Apr 2022 05:47:05 +0000 The post Rare Natural Phenomenon Observed in Saint Petersburg appeared first on English Russia. Full Article Photos Russian Nature saint-petersburg
ural ‘The Super Natural,’ or How to Write about ‘Woo’ By blog.chasclifton.com Published On :: Thu, 05 Sep 2024 22:24:48 +0000 I blogged here before about things disappearing in my house — kitchen utensils, corkscrews, keys, etc. (See “Pixie Problems, or Working Things Out with the ‘Cousins’ (1)” and Part 2, Part 3, and Part 4.) Things have been better since then. … Continue reading → Full Article Uncategorized academia Goddess paranormal writing
ural How to spend a weekend in Malaga, the cultural gateway to Andalucía By www.telegraph.co.uk Published On :: Sun, 08 Sep 2024 17:00:00 GMT Full Article topics:places/europe structure:travel/nightlife topics:places/malaga structure:travel/hotels storytype:standard travel-entity:article topics:places/andalusia topics:places/spain structure:travel/destination-guides-100 structure:travel structure:travel/attractions structure:travel/bars structure:better-life/better-life-evergreen structure:better-life/better-life-guide
ural Event Report: The Inaugural Mt. Prevost DH Combine Invitational By www.pinkbike.com Published On :: Sun, 10 Nov 2024 00:00:00 PST The goal was to facilitate an event that would connect industry and unsigned U15-U17 Canadian riders in a meaningful, personal way that would result in a first hand learning experience about racing on the World Cup circuit.( Photos: 13, Comments: 31 ) Full Article
ural Need a break from politics? Marvel at the 'Vanishing Treasures' of the natural world By www.npr.org Published On :: Thu, 07 Nov 2024 11:56:29 -0500 With 23 short essays on creatures ranging from the wombat to the spider, Katherine Rundell's new book is essential reading for anyone whose wonder could use a jumpstart. Full Article
ural Florida Lawmakers Want Accessible Liquefied Natural gas By shark-tank.com Published On :: Wed, 20 Mar 2019 19:14:54 +0000 “This bill makes American liquefied natural gas accessible and cost-effective to regional allies." The post Florida Lawmakers Want Accessible Liquefied Natural gas appeared first on Shark Tank. Full Article Featured florida Florida Politics Jacksonville venezuela
ural Red Hat is Acquiring AI Optimization Startup Neural Magic By linux.slashdot.org Published On :: 2024-11-12T21:32:00+00:00 Red Hat, the IBM-owned open source software firm, is acquiring Neural Magic, a startup that optimizes AI models to run faster on commodity processors and GPUs. From a report: The terms of the deal weren't disclosed. MIT research scientist Alex Matveev and professor Nir Shavit founded Somerville, Massachusetts-based Neural Magic in 2018, inspired by their work in high-performance execution engines for AI. Neural Magic's software aims to process AI workloads on processors and GPUs at speeds equivalent to specialized AI chips (e.g. TPUs). By running models on off-the-shelf processors, which usually have more available memory, the company's software can realize these performance gains. Big tech companies like AMD and a host of other startups, including NeuReality, Deci, CoCoPie, OctoML and DeepCube, offer some sort of AI optimization software. But Neural Magic is one of the few with a free platform and a collection of open source tools to complement it. Neural Magic had so far managed to raise $50 million in venture capital from backers like Andreessen Horowitz, New Enterprise Associations, Amdocs, Comcast Ventures, Pillar VC and Ridgeline Ventures. Read more of this story at Slashdot. Full Article
ural With Trump Returning To Power, Europe Chief Weighs Idea Of Buying More Natural Gas From US Instead Of Russia By libertyunyielding.com Published On :: Sun, 10 Nov 2024 16:44:07 +0000 By Ireland Owens President of the European Commission Ursula von der Leyen said Friday that she proposed to President-elect Donald Trump the idea that the U.S. could supply more natural gas to Europe to decrease the bloc’s reliance on Russia, according to Barron’s. The EU chief said the topic of tapping U.S. liquefied natural gas […] The post With Trump Returning To Power, Europe Chief Weighs Idea Of Buying More Natural Gas From US Instead Of Russia appeared first on Liberty Unyielding. Full Article Foreign Affairs
ural Which rural area will take the UK’s nuclear waste? By www.bbc.com Published On :: Mon, 09 Sep 2024 00:20:51 GMT The UK's nuclear waste needs a permanent home - but finding a community willing to take it is tricky. Full Article
ural Review: The Cultural Revolution still haunts China By www.chathamhouse.org Published On :: Mon, 30 Jan 2023 13:01:21 +0000 Review: The Cultural Revolution still haunts China The World Today mhiggins.drupal 30 January 2023 Tania Branigan’s searching ‘Red Memory’ reveals the costs to Chinese society of not addressing that upheaval’s lingering injustices, writes Nathan Law. Red Memory: Living, Remembering and Forgetting China’s Cultural RevolutionTania Branigan, Faber, £20 The Cultural Revolution, a decade-long socio-political upheaval initiated by Chairman Mao Zedong in 1966, caused as many as two million deaths and reshaped China. Under the influence of Mao’s personality cult, an entire nation was mobilized to purge the ‘reactionary elements’ in society and the Chinese Communist Party through public denunciation and demolition of traditional heritages. Children turned on their parents; pupils murdered their teachers, and those who survived the summary public trials were often banished – as a young Xi Jinping himself was, living in a cave for seven years, after his father fell from favour. Impossible moral choices In her engaging and sensitive narrative account of the revolution’s upheaval and its consequences, Tania Branigan, the Guardian’s China correspondent between 2008 and 2015, speaks to some of those who survived those terrible years, considers their impossible moral choices and explores the far-reaching legacy of the revolution in present-day China. Mao urged the party to cleanse itself of its ‘class enemies’: ‘capitalists’ such as landowners and shopkeepers, but also artists, farmers and university professors. Often their family members were tainted by association and persecuted. Branigan captures the awful sense of intimate betrayal and tragedy nowhere more than in the testimony of Zhang Hongbing, a lawyer turned zealous Red Guard. What I did to my mother was worse even than to an animal Zhang Hongbing, former Red Guard Zhang denounced his mother, a hospital worker, as a ‘counter-revolutionary’ because her father owned land. She was eventually executed but not before her son struck her twice during her arrest to show his party loyalty. ‘What I did to my mother was worse even than to an animal,’ the remorseful Zhang tells Branigan. Zhang points out that his actions were far from uncommon: ‘The whole country was doing it.’ This unreconciled sense of betrayal and fear still blights China: ‘Our society is ethically hollow. If we trace these problems to their roots, we are likely to find them in the Cultural Revolution,’ one survivor is quoted as writing. Branigan encapsulates the difficulties around reconciliation and remembering in the story of Song Binbin. As a schoolgirl in 1966, she and two classmates were the first to pin up a poster attacking teachers for urging students to focus on their work instead of the revolution. Song’s classmates then beat the school vice principal Bian Zhongyun to death in the playground. The case was never properly investigated, and the death was dismissed as an accident. The pain of remembering In 2014, Song apologized publicly for the poster and expressed a sense of guilt for not intervening on Bian’s behalf. But Bian’s widower rejected the apology. Song did not speak to Branigan herself, instead allowing her friends to speak in her defence. ‘They had spoken of truth and reconciliation, but not once of justice. Every remark brought them towards closure, not accountability,’ Branigan writes. The inability to come to terms with the past pervades the book, most of whose interviewees express feelings of resentment, fear and shame about the Cultural Revolution. I sensed the same emotions when, as a boy, I talked to a neighbour in Hong Kong who was then in his 70s. He escaped from China in the late 1960s due to political and economic strains. He simply nodded and fell silent when I asked him to elaborate. The Cultural Revolution warrants no more than a few paragraphs in official textbooks As Branigan writes: ‘Most Cultural Revolution survivors had learnt to bend with the will of the time; not only to do as they were told but to imply that doing so was their own idea. It was better – safer – to stay silent or lie.’ This collective trauma is exacerbated by official unwillingness to address the past. The Cultural Revolution warrants no more than a few paragraphs in official textbooks with no mention of the suffering it unleashed. Documents of the period that might tarnish the CCP remain unavailable; any attempts to interrogate the Cultural Revolution are condemned as ‘historical nihilism’ by the party. Full Article
ural Naturally occurring hotspot cancer mutations in G{alpha}13 promote oncogenic signaling [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-04T00:06:06-08:00 Heterotrimeric G-proteins are signaling switches broadly divided into four families based on the sequence and functional similarity of their Gα subunits: Gs, Gi/o, Gq/11, and G12/13. Artificial mutations that activate Gα subunits of each of these families have long been known to induce oncogenic transformation in experimental systems. With the advent of next-generation sequencing, activating hotspot mutations in Gs, Gi/o, or Gq/11 proteins have also been identified in patient tumor samples. In contrast, patient tumor-associated G12/13 mutations characterized to date lead to inactivation rather than activation. By using bioinformatic pathway analysis and signaling assays, here we identified cancer-associated hotspot mutations in Arg-200 of Gα13 (encoded by GNA13) as potent activators of oncogenic signaling. First, we found that components of a G12/13-dependent signaling cascade that culminates in activation of the Hippo pathway effectors YAP and TAZ is frequently altered in bladder cancer. Up-regulation of this signaling cascade correlates with increased YAP/TAZ activation transcriptional signatures in this cancer type. Among the G12/13 pathway alterations were mutations in Arg-200 of Gα13, which we validated to promote YAP/TAZ-dependent (TEAD) and MRTF-A/B-dependent (SRE.L) transcriptional activity. We further showed that this mechanism relies on the same RhoGEF-RhoGTPase cascade components that are up-regulated in bladder cancers. Moreover, Gα13 Arg-200 mutants induced oncogenic transformation in vitro as determined by focus formation assays. In summary, our findings on Gα13 mutants establish that naturally occurring hotspot mutations in Gα subunits of any of the four families of heterotrimeric G-proteins are putative cancer drivers. Full Article
ural Thematic review series: Adipocyte Biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis By www.jlr.org Published On :: 2007-12-01 Dawn L. BrasaemleDec 1, 2007; 48:2547-2559Thematic Reviews Full Article
ural Sir David Attenborough and the BBC Studios Natural History Unit awarded Chatham House Prize 2019 for ocean advocacy By www.chathamhouse.org Published On :: Mon, 18 Nov 2019 13:13:54 +0000 Sir David Attenborough and the BBC Studios Natural History Unit awarded Chatham House Prize 2019 for ocean advocacy News Release sysadmin 18 November 2019 The 2019 Chatham House Prize is awarded to Sir David Attenborough and Julian Hector, head of BBC Studios Natural History Unit, for the galvanizing impact of the Blue Planet II series on tackling ocean plastic pollution. Full Article
ural Functional and structural characterization of allosteric activation of phospholipase Cϵ by Rap1A [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-04T00:06:05-08:00 Phospholipase Cε (PLCε) is activated downstream of G protein–coupled receptors and receptor tyrosine kinases through direct interactions with small GTPases, including Rap1A and Ras. Although Ras has been reported to allosterically activate the lipase, it is not known whether Rap1A has the same ability or what its molecular mechanism might be. Rap1A activates PLCε in response to the stimulation of β-adrenergic receptors, translocating the complex to the perinuclear membrane. Because the C-terminal Ras association (RA2) domain of PLCε was proposed to the primary binding site for Rap1A, we first confirmed using purified proteins that the RA2 domain is indeed essential for activation by Rap1A. However, we also showed that the PLCε pleckstrin homology (PH) domain and first two EF hands (EF1/2) are required for Rap1A activation and identified hydrophobic residues on the surface of the RA2 domain that are also necessary. Small-angle X-ray scattering showed that Rap1A binding induces and stabilizes discrete conformational states in PLCε variants that can be activated by the GTPase. These data, together with the recent structure of a catalytically active fragment of PLCε, provide the first evidence that Rap1A, and by extension Ras, allosterically activate the lipase by promoting and stabilizing interactions between the RA2 domain and the PLCε core. Full Article
ural Structural basis for allosteric regulation of pyruvate kinase M2 by phosphorylation and acetylation [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme and transcriptional coactivator and is critical for tumor metabolism. In cancer cells, native tetrameric PKM2 is phosphorylated or acetylated, which initiates a switch to a dimeric/monomeric form that translocates into the nucleus, causing oncogene transcription. However, it is not known how these post-translational modifications (PTMs) disrupt the oligomeric state of PKM2. We explored this question via crystallographic and biophysical analyses of PKM2 mutants containing residues that mimic phosphorylation and acetylation. We find that the PTMs elicit major structural reorganization of the fructose 1,6-bisphosphate (FBP), an allosteric activator, binding site, impacting the interaction with FBP and causing a disruption in oligomerization. To gain insight into how these modifications might cause unique outcomes in cancer cells, we examined the impact of increasing the intracellular pH (pHi) from ∼7.1 (in normal cells) to ∼7.5 (in cancer cells). Biochemical studies of WT PKM2 (wtPKM2) and the two mimetic variants demonstrated that the activity decreases as the pH is increased from 7.0 to 8.0, and wtPKM2 is optimally active and amenable to FBP-mediated allosteric regulation at pHi 7.5. However, the PTM mimetics exist as a mixture of tetramer and dimer, indicating that physiologically dimeric fraction is important and might be necessary for the modified PKM2 to translocate into the nucleus. Thus, our findings provide insight into how PTMs and pH regulate PKM2 and offer a broader understanding of its intricate allosteric regulation mechanism by phosphorylation or acetylation. Full Article
ural The EU’s Un-Common Agricultural Policy By www.chathamhouse.org Published On :: Fri, 27 Sep 2019 12:50:01 +0000 The EU’s Un-Common Agricultural Policy 21 October 2019 — 8:30AM TO 10:00AM Anonymous (not verified) 27 September 2019 Chatham House | 10 St James's Square | London | SW1Y 4LE Despite its name, the EU’s Common Agricultural Policy (CAP) provides support to the agricultural sector that varies widely between the 27 member states. The OECD calculates the extent of this support at the EU level but members have blocked the organization calculating support levels for individual EU members. Overall, the EU’s producer support is equivalent to 20 per cent of farm income which is well-above the levels seen in the US at 12.2 per cent and China at 14.3 per cent. This roundtable will discuss the first estimates of support levels by EU countries produced by Ian Mitchell from the Center for Global Development. It will look at both direct subsidies under the CAP and those that inflate market prices. The discussion will consider the implications for EU finance, for the potential role of EU subsidy reform and for the UK’s options after Brexit. Attendance at this event is by invitation only. Full Article
ural Error analysis for deep neural network approximations of parametric hyperbolic conservation laws By www.ams.org Published On :: Mon, 21 Oct 2024 15:01 EDT T. De Ryck and S. Mishra Math. Comp. 93 (), 2643-2677. Abstract, references and article information Full Article
ural Natural Resources & Economic Development - 11/14/2024 By capitol.texas.gov Published On :: Time: 10:00 AM, Location: E1.012 (Hearing Room) Full Article
ural Managing natural resources By www.chathamhouse.org Published On :: Thu, 16 Jan 2020 12:57:26 +0000 Managing natural resources Research analyzing options for the sustainable management of natural resources and how to use them in a way that enhances the resilience of ecosystems. nfaulds-adams… 16 January 2020 Areas of focus include examining what is the future for fossil fuels and other extractive industries (especially coal, oil and natural gas), forest governance in light of continued illegal logging and deforestation, and ocean governance. Natural resources are vital for the future sustainability of major industries such as agriculture, mining, tourism, fisheries and forestry. Research is carried out in areas such as land use planning, water management, biodiversity conservation, and the scientific and technical understanding of resources governance. Full Article
ural Structural and biochemical characteristics of two Staphylococcus epidermidis RNase J paralogs RNase J1 and RNase J2 [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-04T00:06:06-08:00 RNase J enzymes are metallohydrolases that are involved in RNA maturation and RNA recycling, govern gene expression in bacteria, and catalyze both exonuclease and endonuclease activity. The catalytic activity of RNase J is regulated by multiple mechanisms which include oligomerization, conformational changes to aid substrate recognition, and the metal cofactor at the active site. However, little is known of how RNase J paralogs differ in expression and activity. Here we describe structural and biochemical features of two Staphylococcus epidermidis RNase J paralogs, RNase J1 and RNase J2. RNase J1 is a homodimer with exonuclease activity aided by two metal cofactors at the active site. RNase J2, on the other hand, has endonuclease activity and one metal ion at the active site and is predominantly a monomer. We note that the expression levels of these enzymes vary across Staphylococcal strains. Together, these observations suggest that multiple interacting RNase J paralogs could provide a strategy for functional improvisation utilizing differences in intracellular concentration, quaternary structure, and distinct active site architecture despite overall structural similarity. Full Article
ural Characterizing human {alpha}-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins. Additional modification of the glycan core by α-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an α-1,6-fucosyltransferase (FUT8). The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality. Elevated core fucosylation has also been identified in several human cancers. However, the structural basis for FUT8 substrate specificity remains unknown.Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity. The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor-binding subsite. Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity. The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis. These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems. Full Article
ural A structural and kinetic survey of GH5_4 endoglucanases reveals determinants of broad substrate specificity and opportunities for biomass hydrolysis [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Broad-specificity glycoside hydrolases (GHs) contribute to plant biomass hydrolysis by degrading a diverse range of polysaccharides, making them useful catalysts for renewable energy and biocommodity production. Discovery of new GHs with improved kinetic parameters or more tolerant substrate-binding sites could increase the efficiency of renewable bioenergy production even further. GH5 has over 50 subfamilies exhibiting selectivities for reaction with β-(1,4)–linked oligo- and polysaccharides. Among these, subfamily 4 (GH5_4) contains numerous broad-selectivity endoglucanases that hydrolyze cellulose, xyloglucan, and mixed-linkage glucans. We previously surveyed the whole subfamily and found over 100 new broad-specificity endoglucanases, although the structural origins of broad specificity remained unclear. A mechanistic understanding of GH5_4 substrate specificity would help inform the best protein design strategies and the most appropriate industrial application of broad-specificity endoglucanases. Here we report structures of 10 new GH5_4 enzymes from cellulolytic microbes and characterize their substrate selectivity using normalized reducing sugar assays and MS. We found that GH5_4 enzymes have the highest catalytic efficiency for hydrolysis of xyloglucan, glucomannan, and soluble β-glucans, with opportunistic secondary reactions on cellulose, mannan, and xylan. The positions of key aromatic residues determine the overall reaction rate and breadth of substrate tolerance, and they contribute to differences in oligosaccharide cleavage patterns. Our new composite model identifies several critical structural features that confer broad specificity and may be readily engineered into existing industrial enzymes. We demonstrate that GH5_4 endoglucanases can have broad specificity without sacrificing high activity, making them a valuable addition to the biomass deconstruction toolset. Full Article
ural Snapshots during the catalytic cycle of a histidine acid phytase reveal an induced-fit structural mechanism [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Highly engineered phytases, which sequentially hydrolyze the hexakisphosphate ester of inositol known as phytic acid, are routinely added to the feeds of monogastric animals to improve phosphate bioavailability. New phytases are sought as starting points to further optimize the rate and extent of dephosphorylation of phytate in the animal digestive tract. Multiple inositol polyphosphate phosphatases (MINPPs) are clade 2 histidine phosphatases (HP2P) able to carry out the stepwise hydrolysis of phytate. MINPPs are not restricted by a strong positional specificity making them attractive targets for development as feed enzymes. Here, we describe the characterization of a MINPP from the Gram-positive bacterium Bifidobacterium longum (BlMINPP). BlMINPP has a typical HP2P-fold but, unusually, possesses a large α-domain polypeptide insertion relative to other MINPPs. This insertion, termed the U-loop, spans the active site and contributes to substrate specificity pockets underpopulated in other HP2Ps. Mutagenesis of U-loop residues reveals its contribution to enzyme kinetics and thermostability. Moreover, four crystal structures of the protein along the catalytic cycle capture, for the first time in an HP2P, a large ligand-driven α-domain motion essential to allow substrate access to the active site. This motion recruits residues both downstream of a molecular hinge and on the U-loop to participate in specificity subsites, and mutagenesis identified a mobile lysine residue as a key determinant of positional specificity of the enzyme. Taken together, these data provide important new insights to the factors determining stability, substrate recognition, and the structural mechanism of hydrolysis in this industrially important group of enzymes. Full Article
ural Evolving the naturally compromised chorismate mutase from Mycobacterium tuberculosis to top performance [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Chorismate mutase (CM), an essential enzyme at the branch-point of the shikimate pathway, is required for the biosynthesis of phenylalanine and tyrosine in bacteria, archaea, plants, and fungi. MtCM, the CM from Mycobacterium tuberculosis, has less than 1% of the catalytic efficiency of a typical natural CM and requires complex formation with 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase for high activity. To explore the full potential of MtCM for catalyzing its native reaction, we applied diverse iterative cycles of mutagenesis and selection, thereby raising kcat/Km 270-fold to 5 × 105 m−1s−1, which is even higher than for the complex. Moreover, the evolutionarily optimized autonomous MtCM, which had 11 of its 90 amino acids exchanged, was stabilized compared with its progenitor, as indicated by a 9 °C increase in melting temperature. The 1.5 Å crystal structure of the top-evolved MtCM variant reveals the molecular underpinnings of this activity boost. Some acquired residues (e.g. Pro52 and Asp55) are conserved in naturally efficient CMs, but most of them lie beyond the active site. Our evolutionary trajectories reached a plateau at the level of the best natural enzymes, suggesting that we have exhausted the potential of MtCM. Taken together, these findings show that the scaffold of MtCM, which naturally evolved for mediocrity to enable inter-enzyme allosteric regulation of the shikimate pathway, is inherently capable of high activity. Full Article
ural Hydrogen/deuterium exchange memory NMR reveals structural epitopes involved in IgE cross-reactivity of allergenic lipid transfer proteins [Protein Structure and Folding] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Identification of antibody-binding epitopes is crucial to understand immunological mechanisms. It is of particular interest for allergenic proteins with high cross-reactivity as observed in the lipid transfer protein (LTP) syndrome, which is characterized by severe allergic reactions. Art v 3, a pollen LTP from mugwort, is frequently involved in this cross-reactivity, but no antibody-binding epitopes have been determined so far. To reveal human IgE-binding regions of Art v 3, we produced three murine high-affinity mAbs, which showed 70–90% coverage of the allergenic epitopes from mugwort pollen–allergic patients. As reliable methods to determine structural epitopes with tightly interacting intact antibodies under native conditions are lacking, we developed a straightforward NMR approach termed hydrogen/deuterium exchange memory (HDXMEM). It relies on the slow exchange between the invisible antigen-mAb complex and the free 15N-labeled antigen whose 1H-15N correlations are detected. Due to a memory effect, changes of NH protection during antibody binding are measured. Differences in H/D exchange rates and analyses of mAb reactivity to homologous LTPs revealed three structural epitopes: two partially cross-reactive regions around α-helices 2 and 4 as well as a novel Art v 3–specific epitope at the C terminus. Protein variants with exchanged epitope residues confirmed the antibody-binding sites and revealed strongly reduced IgE reactivity. Using the novel HDXMEM for NMR epitope mapping allowed identification of the first structural epitopes of an allergenic pollen LTP. This knowledge enables improved cross-reactivity prediction for patients suffering from LTP allergy and facilitates design of therapeutics. Full Article
ural Structural transitions in Orb2 prion-like domain relevant for functional aggregation in memory consolidation [Molecular Biophysics] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 The recent structural elucidation of ex vivo Drosophila Orb2 fibrils revealed a novel amyloid formed by interdigitated Gln and His residue side chains belonging to the prion-like domain. However, atomic-level details on the conformational transitions associated with memory consolidation remain unknown. Here, we have characterized the nascent conformation and dynamics of the prion-like domain (PLD) of Orb2A using a nonconventional liquid-state NMR spectroscopy strategy based on 13C detection to afford an essentially complete set of 13Cα, 13Cβ, 1Hα, and backbone 13CO and 15N assignments. At pH 4, where His residues are protonated, the PLD is disordered and flexible, except for a partially populated α-helix spanning residues 55–60, and binds RNA oligos, but not divalent cations. At pH 7, in contrast, His residues are predominantly neutral, and the Q/H segments adopt minor populations of helical structure, show decreased mobility and start to self-associate. At pH 7, the His residues do not bind RNA or Ca2+, but do bind Zn2+, which promotes further association. These findings represent a remarkable case of structural plasticity, based on which an updated model for Orb2A functional amyloidogenesis is suggested. Full Article
ural Towards just transition in Africa: Green financing for nature-based solutions and rural resilience By www.chathamhouse.org Published On :: Thu, 30 Jun 2022 10:52:13 +0000 Towards just transition in Africa: Green financing for nature-based solutions and rural resilience 21 July 2022 — 9:30AM TO 1:00PM Anonymous (not verified) 30 June 2022 Libreville and online This hybrid event in Libreville explores just transition policy and green financing for nature-based solutions, with a particular focus on the integration of job creation priorities in conservation and rural resilience. Global climate policies towards a ‘just transition’ under the Paris Agreement should align with and support African states’ national sustainable development priorities – in particular, the need for decent and fair job creation, as well as resilient and sustainable land, environment, and ecosystem management policies. Achieving green growth requires innovative and more accessible financing models, especially as wealthy nations’ financial pledges have fallen short. Ahead of the ‘African COP27’ set to take place in Egypt in November 2022, there is a need for transformational strategic thinking and context-specific action from African governments, civil society, businesses and financiers, in their green financing demands and national implementation plans. Preservation of biodiversity and nature is not only critical in the global fight against climate change but is also vital for conservation-based economic development. Natural capital stocks, such as terrestrial and marine ecosystems and biodiversity, produce benefits that support societal and individual well-being and economic prosperity, such as clean air, fresh water, regulation of water flows and pollination of crops – while also acting as important carbon sinks. Financing environmental protection must go beyond compensation and contribute to creating fair social and economic conditions for incentivizing conservation. At this hybrid event in Libreville, participants will discuss green financing for nature-based solutions, particularly the integration of plans for job creation in conservation and rural resilience within just transition planning. This event is part of a series on Towards Just Transition: Connecting Green Financing and Sustainable Job Creation in Africa, supported by the Chatham House Sustainability Accelerator. This event will be held in French and English with simultaneous interpretation. This event will also be broadcast live on the Chatham House Africa Programme’s Facebook page. Green financing for nature-based solutions and rural resilience - English agenda (PDF) Green financing for nature-based solutions and rural resilience - French agenda (PDF) Full Article
ural A natural climate change priority for Africa By www.chathamhouse.org Published On :: Wed, 28 Sep 2022 15:39:21 +0000 A natural climate change priority for Africa Expert comment LJefferson 28 September 2022 Nature-based solutions can protect African nations’ shared natural endowment and meet the needs of their people. Africa’s principal climate change negotiators have long understood the important contribution of ‘nature-based solutions’ (NBS) in delivering land (and sea) based options as part of the goals of the Paris Agreement. Limiting temperature rises to only 1.5°C by 2050 will demand finding innovative ways to protect Africa’s vast natural endowment that also meets the equally acute needs of its people. Nature-based solutions may do both. Decision-makers on the continent and across the world need to understand that ‘business as usual’ cannot be an option given the potential for loss of life, conflict and chaos. The urgency for Africa cannot be overstated. At a Chatham House conference in Libreville, the Gabonese minister for the environment highlighted that if global warming surges by 2.5° or 3°C the impact would be at least 6°C for Africa. Decision-makers on the continent and across the world need to understand that ‘business as usual’ cannot be an option given the potential for loss of life, conflict and chaos. Adaption, mitigation, or both? Although adaptation to climate change has hitherto tended to be the continent’s main concern, there has also been growing recognition of the ways that Africa’s natural environments, from forests and grasslands, to peatlands and coastal and marine ecosystems, all also mitigate its impacts by sequestering carbon. The Congo Basin alone is said to store upwards of 4 per cent of global emissions annually. Arguing that African states should slow the development of their economies in response to a crisis born of the already-industrialized world does not find a responsive audience in a continent hungry for jobs and opportunity. These environments are under increasing pressure. Deforestation is a sad reality, caused mostly by unsustainable and extensive agricultural practices focused on cash crops for export more than food production to feed local populations. And arguing that African states and peoples should slow the development of their economies and infrastructure in response to a crisis born of the already-industrialized world does not find a responsive audience in a continent hungry for jobs and opportunity. Nature-based solutions offer an answer to this conundrum. There is growing evidence that natural habitats both help avoid losses from climate change-related disasters and can drive economic growth. There is thus potential for NBS to tackle both adaptation and mitigation challenges at relatively low cost. NBS – the rocky road from commitment to policy It was logical therefore for Africa and like-minded countries to work to integrate NBS more strongly into the climate change agenda at COP26. The final Glasgow Climate Pact duly emphasized the importance of protecting ecosystems. The Global Forest Finance Pledge signed in the margins was also significant. African focus, with COP 27 in Egypt soon to take place, is now on domestic implementation and delivery of these pledges. The new African Union Climate Change and Resilient Development strategy (2022-2032) sets out many of the challenges and opportunities. Choosing the right development pathway is tough, requiring political will and inclusive governance. Besides the challenge of securing alternative national revenue if a country moves away from fossil-intensive fuels – particularly acute for Africa’s resource-producing states – there is a dizzying array of policy decisions to be taken. African governments need to choose the most appropriate renewable energy sources, secure alternative livelihoods and continue to meet basic needs of the most vulnerable in the context of radical restructuring. Towards African solutions There can be no one-size-fits-all answer to these questions – it is sadly still necessary to underline the enormous geographic, cultural and political diversity of the continent – but African experts have begun to draw together some emerging common themes from work already underway. Maintaining the ‘status quo’ in agricultural practices is no longer an option. Emphasis on sustainable agriculture is urgently needed andthat includes the elaboration of a ‘new deal’ between nature and people. Conservation also needs to be reframed as an economic opportunity, particularly in the elaboration and development of ecosystem services that deliver the true value of Africa’s forests, and that involve, value and reward local communities, respecting their rights and livelihoods. Maintaining the ‘status quo’ in agricultural practices is no longer an option. Emphasis on sustainable agriculture is urgently needed. Regional cooperation is likewise key, including on the management of forest, wildlife and water resources – Africa’s ecosystems do not respect arbitrary political boundaries, and accomplishing the dual feat of protecting cross-border systems at the same time as realizing their economic potential will demand effective collaboration, as well as training, education and communication at all levels. The imperative of finance A further imperative will be securing sufficient developed country financing – whether that be to secure value for net sequestration and effective forest management or for models of context-appropriate ‘smarter’ sustainable rural conservation and ecosystem resilience. Full Article
ural WITHDRAWN: Structural and mechanistic studies of hydroperoxide conversions catalyzed by a CYP74 clan epoxy alcohol synthase from amphioxus (Branchiostoma floridae) [Research Articles] By www.jlr.org Published On :: 2014-03-04T09:59:12-08:00 This manuscript has been withdrawn by the Author. Full Article
ural The structural basis for monoclonal antibody 5D2 binding to the tryptophan-rich loop of lipoprotein lipase [Research Articles] By www.jlr.org Published On :: 2020-10-01T00:05:17-07:00 For three decades, the LPL–specific monoclonal antibody 5D2 has been used to investigate LPL structure/function and intravascular lipolysis. 5D2 has been used to measure LPL levels, block the triglyceride hydrolase activity of LPL, and prevent the propensity of concentrated LPL preparations to form homodimers. Two early studies on the location of the 5D2 epitope reached conflicting conclusions, but the more convincing report suggested that 5D2 binds to a tryptophan (Trp)-rich loop in the carboxyl terminus of LPL. The same loop had been implicated in lipoprotein binding. Using surface plasmon resonance, we showed that 5D2 binds with high affinity to a synthetic LPL peptide containing the Trp-rich loop of human (but not mouse) LPL. We also showed, by both fluorescence and UV resonance Raman spectroscopy, that the Trp-rich loop binds lipids. Finally, we used X-ray crystallography to solve the structure of the Trp-rich peptide bound to a 5D2 Fab fragment. The Trp-rich peptide contains a short α-helix, with two Trps projecting into the antigen recognition site. A proline substitution in the α-helix, found in mouse LPL, is expected to interfere with several hydrogen bonds, explaining why 5D2 cannot bind to mouse LPL. Full Article
ural Nuclear Disarmament and the Protection of Cultural Heritage By www.chathamhouse.org Published On :: Fri, 06 Oct 2017 13:24:22 +0000 Nuclear Disarmament and the Protection of Cultural Heritage Research paper sysadmin 6 October 2017 States possessing nuclear weapons should be called upon to consider and publish the risks posed to cultural heritage, and their mitigation strategies, in their nuclear-weapons doctrines and policies. — A woman walks on the roof of the Great Mosque of Djenné, a World Heritage Site, after praying. Photo: United Nations. Summary Renewed risk assessments for nuclear weapons and policies are taking place around the world in light of nuclear modernization and the changing geostrategic environment that is making the use of nuclear weapons more likely. As such the humanitarian impacts of nuclear weapons and tests have received increased attention. However, the effect on cultural heritage has so far been neglected. The potential for armed conflict to destroy cultural heritage has been recognized in international law since 1954. There is significant evidence on the impact of nuclear weapons on cultural heritage including the consequences of their use in Hiroshima and Nagasaki and the effect of nuclear-testing programmes in places of cultural significance since 1945. States that possess nuclear weapons have increased liabilities and responsibilities to protect cultural heritage and cultural rights. The need to protect cultural heritage should strengthen the case for reducing and eliminating nuclear weapons. Failure to take into account the protection of heritage in the development of nuclear weapons policies – including disarmament, non-proliferation and arms-control negotiations – significantly undermines states’ existing commitments to protecting heritage threatened by conflict. Risk assessments of the impact of nuclear weapons on cultural heritage and important cultural artefacts – and methods of preventing such catastrophic damage – should be part of protecting cultural heritage in every country and the subject of informed public debate. A new body of knowledge on the full range of nuclear weapons impacts would introduce a fresh perspective to inform decision-makers, international organizations and the public in thinking about nuclear weapons policies and practices. Risk and resilience frameworks, which provide sets of solutions for risk assessments, would allow assessments of nuclear weapons threats to heritage and highlight vulnerabilities that need to be addressed. Such frameworks would provide a basis for policymakers to identify the world’s cultural heritage most at risk and help develop mitigation strategies to ensure that it is protected. In particular, states possessing nuclear weapons should be called upon to consider and publish the risks posed to cultural heritage, and their mitigation strategies, in their nuclear weapons doctrines and policies, as a contribution to transparency and confidence-building, and as a responsibility to the world’s shared heritage. International organizations, such as the UN Educational, Scientific, and Cultural Organization (UNESCO), have a role to play in bridging security perspectives with protecting cultural heritage. 2017-10-10-nuclear disarmament-cultural-heritage-aghlani-lewis-unal-final (PDF) Full Article
ural Diagnosing social behavioural dynamics of corruption By www.chathamhouse.org Published On :: Wed, 08 Dec 2021 16:52:08 +0000 Diagnosing social behavioural dynamics of corruption Other resource dora.popova 8 December 2021 This interactive toolkit identifies the types of social expectations which sustain selected corrupt practices and provides behaviourally-informed recommendations for changing them. When tackling a problem as complex as corruption, it is important to understand why and how people behave in different situations where corruption occurs. In contexts where it is easier to engage in corruption than avoid it, identifying the social expectations and informal rules which sustain corrupt practices can advance corruption prevention and deepen collective action. Behavioural approaches to corruption offer a better understanding of diverse social settings, group dynamics, power distribution, social motivations, and expectations that contribute to a more tolerant environment for certain forms of the phenomenon. They are also highly complementary to traditional corruption measures, which tend to focus on the enforcement of legal sanctions and deterrents. Behavioural approaches, especially those inspired by social norms theory, highlight complex social characteristics and informal rules of specific corrupt practices, and effectively support implementation of more dynamic context-specific anti-corruption interventions. Since 2016, the Chatham House Africa programme’s Social Norms and Accountable Governance (SNAG) project has adopted a behavioural approach based on social norms methodology to investigate the social beliefs which motivate different forms of corruption. Drawing on the project’s extensive evidence-gathering and analysis, this toolkit offers users navigable behavioural mapping of contextual factors, beliefs, and expectations surrounding common corrupt practices. It aims to support anti-corruption actors in diagnosing informal rules and social expectations which sustain corruption in some societies. It also proposes behavioural-informed guidance for developing or adapting anti-corruption interventions and activities, so they account for informal rules of behaviour such as social norms. The toolkit supports users to: Identify whether and how widespread corrupt practices are motivated by social beliefs and expectations. Understand how society influences the types of corrupt activity individuals engage in, or avoid, and the factors informing these choices Integrate empirical evidence and behavioural insights into anti-corruption strategies from diagnostics to design, and eventual implementation and evaluation The toolkit presents evidence from SNAG’s research into three key corrupt practices – bribery, embezzlement, and electoral fraud. Each was examined in the context of typical situations in which they occur, such as law enforcement, healthcare, the power sector, voting, and education while critical factors such as religion, gender, and ethnicity were considered. The toolkit presents an overview of specific contexts and behavioural features of the practices and provides behavioural-informed recommendations. It also contains pop-up features with definitions and explanations of key concepts. The toolkit is designed to be expandable, allowing further content and behavioural dynamics to be added. Full Article
ural Optimized incorporation of an unnatural fluorescent amino acid affords measurement of conformational dynamics governing high-fidelity DNA replication [DNA and Chromosomes] By www.jbc.org Published On :: 2020-12-11T00:06:21-08:00 DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication. Full Article
ural Polymerase {gamma} efficiently replicates through many natural template barriers but stalls at the HSP1 quadruplex [Enzymology] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Faithful replication of the mitochondrial genome is carried out by a set of key nuclear-encoded proteins. DNA polymerase γ is a core component of the mtDNA replisome and the only replicative DNA polymerase localized to mitochondria. The asynchronous mechanism of mtDNA replication predicts that the replication machinery encounters dsDNA and unique physical barriers such as structured genes, G-quadruplexes, and other obstacles. In vitro experiments here provide evidence that the polymerase γ heterotrimer is well-adapted to efficiently synthesize DNA, despite the presence of many naturally occurring roadblocks. However, we identified a specific G-quadruplex–forming sequence at the heavy-strand promoter (HSP1) that has the potential to cause significant stalling of mtDNA replication. Furthermore, this structured region of DNA corresponds to the break site for a large (3,895 bp) deletion observed in mitochondrial disease patients. The presence of this deletion in humans correlates with UV exposure, and we have found that efficiency of polymerase γ DNA synthesis is reduced after this quadruplex is exposed to UV in vitro. Full Article
ural Elon Musk's Neuralink Has Implanted Its First Chip in a Human Brain. What's Next? By www.scientificamerican.com Published On :: Tue, 30 Jan 2024 23:30:00 GMT The wealthiest person on Earth has taken the next step toward a commercial brain interface Full Article Health Care Mind & Brain Neurology Biotech
ural Study: Deaths from cardiovascular disease surge among adults 25-64 in rural areas By www.upi.com Published On :: Tue, 12 Nov 2024 06:39:14 -0500 Deaths from cardiovascular disease have surged among adults ages 25 to 64 living in rural areas, a new study shows. Full Article
ural VA to eliminate copays for telehealth, expand online emergency care to rural veterans By www.upi.com Published On :: Mon, 11 Nov 2024 23:53:12 -0500 The U.S. Department of Veterans Affairs announced plans Monday to eliminate copayments for all VA telehealth services, while expanding online emergency care access for rural veterans. Full Article
ural Why spending smarter beats bigger budgets | Karthik Muralidharan By www.ted.com Published On :: Mon, 11 Nov 2024 15:54:37 +0000 Billions of dollars are poured into global development every year, but results are lacking, says economist Karthik Muralidharan. Diving into an example with public education, he outlines how smarter resource allocation and evidence-based interventions, like learning software that dynamically responds to students and teaches at the level that's right for them, can accelerate global development worldwide — not by spending more, but by spending smarter. Full Article Higher Education
ural Cultural Frame Switching: Different Language, Different Personality By feeds.feedblitz.com Published On :: Thu, 19 Aug 2021 16:07:49 +0000 Bilingual individuals demonstrate different personality characteristics when speaking different languages. Marketers making media and language decisions when addressing multilingual markets should add this finding to their list of influencing factors. The post Cultural Frame Switching: Different Language, Different Personality appeared first on Neuromarketing. Click the icon below to listen. Full Article Neuromarketing bilingual cultural frame switching language
ural Expansion Planned for Urban-Rural Student Exchange Program By blogs.edweek.org Published On :: Fri, 07 Feb 2014 00:00:00 +0000 One Montana nonprofit tries to build connections between rural and urban students with exchange program. Full Article Montana
ural Dual-Language Learning: How Schools Can Invest in Cultural and Linguistic Diversity By blogs.edweek.org Published On :: Wed, 19 Sep 2018 00:00:00 +0000 In this fourth installment on the growth in dual-language learning, the director of dual-language education in Portland, Ore., says schools must have a clear reason for why they are offering dual-language instruction. Full Article Oregon