Beijing briefing: China aims for tech self-reliance The World Today mhiggins.drupal 28 March 2023

Xi Jinping’s new appointments are tasked with a technology led recovery, but they face a daunting task to restore growth, writes Yu Jie.

The three-day state visit to Moscow by President Xi Jinping in March may have eclipsed the National People’s Congress in Beijing a fortnight earlier, but as Xi seeks to establish a new global order with China at its centre, the political events in the Great Hall of People provide an important insight into the country’s longer-term economic plans.

While a new cohort of cabinet members was appointed to sit on the State Council for the next five years, much of the attention remains on China’s economic stimulus plan to enable a rapid post-Covid recovery, as well as proposals to restructure central government.

Mountainous task

Three aspects of this year’s Congress deserve deeper scrutiny: Li Qiang’s confirmation as premier to succeed Li Keqiang’s decade-long subdued tenure under Xi; the extent to which Xi’s new cabinet sheds light on China’s economic and scientific self-reliance; and the unveiling of a major restructuring of central government administration in sectors such as finance and science.

China’s new premier initially faces the mountainous task of restoring growth and market confidence. During a press conference much shorter than his predecessor would hold, Li Qiang praised China’s private business sector and repeated the words ‘China remains open to foreign business’ to address the growing anxieties among foreigners and Chinese private entrepreneurs.

Beside the daunting task of economic recovery, Li Qiang faces another big challenge. Unlike his predecessors, he has never worked as a vice premier and overseen ministries under the State Council. The test for him will be to pursue a sound economic recovery plan while coordinating numerous central government agencies. He will also need to regulate relations among provincial heads who have a tendency to argue endlessly over the distribution of public finances.

Even though Xi is secure in his third term, his involvement in shaping and implementing macro-economic policies is keenly felt. Li Qiang made explicit the State Council under his leadership will be the chief implementor of all policies approved by the president. This is a less equal working partnership with Xi than his predecessors on the State Council enjoyed in the past.

Beijing published its official plan to restructure its central government administration announcing planned cuts of 5 per cent of its civil service. The newly established Central Commission on Finance intends to deal with systemic financial risks and to coordinate the financial regulatory bodies, central bank and Ministry of Finance. This is seen to reflect the Chinese leadership’s growing concern with the poor performance of local government loans and debt as well of the volatility of the property market, all of which threaten huge uncertainty for the economy.

As well as reorganizing the financial sector, Xi’s intention to pursue an integrated national strategy combining economic and scientific self-reliance has led to significant appointments following the Congress. As a starter, a new Central Commission for Science under the party leadership has been established. This commission will focus on providing a renewed impetus to accelerate China’s drive to achieve ‘scientific reliance’ and to ease the choke points in the economy, such as the supply chain for semiconductors.

It remains unclear who will head this new commission or who will be on it, however, as scant detail has been made public. It is seen as a direct response to the tough measures adopted by the United States designed to dent China’s ambitions of technology supremacy.

Departure from the past

New appointees to the Politburo come with substantial backgrounds in science as well as a solid track record of running state-owned enterprises. This is a departure from the past.

Instead of inserting financial specialists, Xi appointed two scientists, Liu Guozhong and Zhang Guoqing, as the vice premiers overseeing science, education and industrial policies. This signals that Xi intends to prioritize science and innovation during his third term. The appointment of technocrats to the State Council is seen as a move to strengthen innovation and prepare the Chinese economy, political system and society for potential external shocks.

Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an α/β-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (compound 1) and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A Trp-186/Trp-187/Tyr-247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in α/β-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, whereas the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single-crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U and provided a new approach for engineering regioselective epoxide hydrolases.

In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,...

Martin R. Larsen
Jul 1, 2005; 4:873-886
Technology

Resetting Africa-Europe relations: From self-deception to economic transformation 28 October 2024 — 12:30PM TO 1:30PM Anonymous (not verified) 16 October 2024 Chatham House and Online

Experts assess the status of ties between Africa and Europe in a rapidly changing world, launching a new book that explores how misconceptions in the relationship can harm Africa’s economic agenda.

The relationship between Africa and Europe has long been shaped by colonial legacies, power imbalance and shifting geopolitical interests.

Almost three years on from the last EU-AU summit in Brussels in February 2022, questions remain over the delivery of headline commitments under the continent-to-continent partnership – ranging from the EU’s Global Gateway infrastructure strategy to wider climate financing promises.

As Africa seeks to strengthen its standing on the global stage, marked by the African Union’s upcoming debut at the G20 summit in November, a critical reassessment of these dynamics is needed to examine whether the continent’s relationship with Europe can overcome stigmatized narratives in search of genuine economic benefit.

At this event, which launches a new book by Professor Carlos Lopes: The Self-Deception Trap: Exploring the Economic Dimensions of Charity Dependency within Africa-Europe Relations, speakers assess the prospects for a transformative shift towards a more equitable and mutually beneficial Africa-Europe partnership.

Elizabeth Wilmshurst CMG appointed Honorary Queen’s Counsel News release jon.wallace 14 January 2022

Founder of the International Law Programme at Chatham House recognized for her major contribution to the law of England and Wales.

Elizabeth Wilmshurst CMG, distinguished fellow of Chatham House’s International Law Programme, has been awarded the title of Honorary Queen’s Counsel (QC Honoris Causa), recognizing her major contribution to the law of England and Wales, outside practice in the courts. The Lord Chancellor will preside over an appointment ceremony at Westminster Hall on 21 March 2022.

Elizabeth founded the International Law Programme at Chatham House and is an academic expert member of Doughty Street Chambers. She was a legal adviser in the United Kingdom diplomatic service between 1974 and 2003. Between 1994 and 1997 she was the Legal Adviser to the United Kingdom mission to the United Nations in New York. She also took part in the negotiations for the establishment of the International Criminal Court.

Throughout her career, Elizabeth has worked to strengthen the role of international law in reducing global tensions, addressing cross-border challenges and promoting individual liberty, including through influential publications at the Institute such as The Chatham House Principles of International Law on the Use of Force in Self-Defence. 

Robin Niblett CMG, Director and Chief Executive of Chatham House said:

‘We are delighted by this award which recognizes Elizabeth’s outstanding contribution to the field of international law, both in government and – on a continuing basis – through the International Law Programme at Chatham House.’

Expert

Expert

Ming-Lun Hsieh and Shunsuke Yamana
Trans. Amer. Math. Soc. 377 (), 5617-5672.
Abstract, references and article information

Nathan Brownlowe, Alcides Buss, Daniel Gonçalves, Jeremy B. Hume, Aidan Sims and Michael F. Whittaker
Trans. Amer. Math. Soc. 377 (), 5513-5560.
Abstract, references and article information

Roland Donninger
Bull. Amer. Math. Soc. 61 (), 659-685.
Abstract, references and article information

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Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 109 variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (KD) as low as 0.8 nm. We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule–positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies.

Thoracic great vessels such as the aorta and subclavian arteries are formed through dynamic remodeling of embryonic pharyngeal arch arteries (PAAs). Previous work has shown that loss of a basic helix-loop-helix transcription factor Hey1 in mice causes abnormal fourth PAA development and lethal great vessel anomalies resembling congenital malformations in humans. However, how Hey1 mediates vascular formation remains unclear. In this study, we revealed that Hey1 in vascular endothelial cells, but not in smooth muscle cells, played essential roles for PAA development and great vessel morphogenesis in mouse embryos. Tek-Cre–mediated Hey1 deletion in endothelial cells affected endothelial tube formation and smooth muscle differentiation in embryonic fourth PAAs and resulted in interruption of the aortic arch and other great vessel malformations. Cell specificity and signal responsiveness of Hey1 expression were controlled through multiple cis-regulatory regions. We found two distal genomic regions that had enhancer activity in endothelial cells and in the pharyngeal epithelium and somites, respectively. The novel endothelial enhancer was conserved across species and was specific to large-caliber arteries. Its transcriptional activity was regulated by Notch signaling in vitro and in vivo, but not by ALK1 signaling and other transcription factors implicated in endothelial cell specificity. The distal endothelial enhancer was not essential for basal Hey1 expression in mouse embryos but may likely serve for Notch-dependent transcriptional control in endothelial cells together with the proximal regulatory region. These findings help in understanding the significance and regulation of endothelial Hey1 as a mediator of multiple signaling pathways in embryonic vascular formation.

Members of the B-cell lymphoma (BCL-2) protein family regulate mitochondrial outer membrane permeabilization (MOMP), a phenomenon in which mitochondria become porous and release death-propagating complexes during the early stages of apoptosis. Pro-apoptotic BCL-2 proteins oligomerize at the mitochondrial outer membrane during MOMP, inducing pore formation. Of current interest are endogenous factors that can inhibit pro-apoptotic BCL-2 mitochondrial outer membrane translocation and oligomerization. A mitochondrial-derived peptide, Humanin (HN), was reported being expressed from an alternate ORF in the mitochondrial genome and inhibiting apoptosis through interactions with the pro-apoptotic BCL-2 proteins. Specifically, it is known to complex with BAX and BID. We recently reported the fibrillation of HN and BAX into β-sheets. Here, we detail the fibrillation between HN and BID. These fibers were characterized using several spectroscopic techniques, protease fragmentation with mass analysis, and EM. Enhanced fibrillation rates were detected with rising temperatures or pH values and the presence of a detergent. BID fibers are similar to those produced using BAX; however, the structures differ in final conformations of the BCL-2 proteins. BID fibers display both types of secondary structure in the fiber, whereas BAX was converted entirely to β-sheets. The data show that two distinct segments of BID are incorporated into the fiber structure, whereas other portions of BID remain solvent-exposed and retain helical structure. Similar analyses show that anti-apoptotic BCL-xL does not form fibers with humanin. These results support a general mechanism of sequestration of pro-apoptotic BCL-2 proteins into fibers by HN to inhibit MOMP.

Environmental factors, such as viral infection, are proposed to play a role in the initiation of autoimmune diabetes. In response to encephalomyocarditis virus (EMCV) infection, resident islet macrophages release the pro-inflammatory cytokine IL-1β, to levels that are sufficient to stimulate inducible nitric oxide synthase (iNOS) expression and production of micromolar levels of the free radical nitric oxide in neighboring β-cells. We have recently shown that nitric oxide inhibits EMCV replication and EMCV-mediated β-cell lysis and that this protection is associated with an inhibition of mitochondrial oxidative metabolism. Here we show that the protective actions of nitric oxide against EMCV infection are selective for β-cells and associated with the metabolic coupling of glycolysis and mitochondrial oxidation that is necessary for insulin secretion. Inhibitors of mitochondrial respiration attenuate EMCV replication in β-cells, and this inhibition is associated with a decrease in ATP levels. In mouse embryonic fibroblasts (MEFs), inhibition of mitochondrial metabolism does not modify EMCV replication or decrease ATP levels. Like most cell types, MEFs have the capacity to uncouple the glycolytic utilization of glucose from mitochondrial respiration, allowing for the maintenance of ATP levels under conditions of impaired mitochondrial respiration. It is only when MEFs are forced to use mitochondrial oxidative metabolism for ATP generation that mitochondrial inhibitors attenuate viral replication. In a β-cell selective manner, these findings indicate that nitric oxide targets the same metabolic pathways necessary for glucose stimulated insulin secretion for protection from viral lysis.

Gle1 is a conserved, essential regulator of DEAD-box RNA helicases, with critical roles defined in mRNA export, translation initiation, translation termination, and stress granule formation. Mechanisms that specify which, where, and when DDXs are targeted by Gle1 are critical to understand. In addition to roles for stress-induced phosphorylation and inositol hexakisphosphate binding in specifying Gle1 function, Gle1 oligomerizes via its N-terminal domain in a phosphorylation-dependent manner. However, a thorough analysis of the role for Gle1 self-association is lacking. Here, we find that Gle1 self-association is driven by two distinct regions: a coiled-coil domain and a novel 10-amino acid aggregation-prone region, both of which are necessary for proper Gle1 oligomerization. By exogenous expression in HeLa cells, we tested the function of a series of mutations that impact the oligomerization domains of the Gle1A and Gle1B isoforms. Gle1 oligomerization is necessary for many, but not all aspects of Gle1A and Gle1B function, and the requirements for each interaction domain differ. Whereas the coiled-coil domain and aggregation-prone region additively contribute to competent mRNA export and stress granule formation, both self-association domains are independently required for regulation of translation under cellular stress. In contrast, Gle1 self-association is dispensable for phosphorylation and nonstressed translation initiation. Collectively, we reveal self-association functions as an additional mode of Gle1 regulation to ensure proper mRNA export and translation. This work also provides further insight into the mechanisms underlying human gle1 disease mutants found in prenatally lethal forms of arthrogryposis.

Hideaki Kuge
Dec 1, 2020; 61:1747-1763
Research Articles

In SAS Customer Intelligence Studio, you can choose to create a new calculated variable in the Edit Value dialog box when you populate a treatment custom detail. Following creation of the new calculated

Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remains largely unknown. Sphingolipids are bioactive components of most foods and are also produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet–microbiome interactions. Here, we used a click chemistry–based approach to track the incorporation of bioorthogonal dietary omega-alkynyl sphinganine (sphinganine alkyne [SAA]) into the murine gut microbial community (Bioorthogonal labeling). We identified microbial and SAA-specific metabolic products through fluorescence-based sorting of SAA-containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together, this approach, termed Bioorthogonal labeling-Sort-Seq-Spec (BOSSS), revealed that SAA assimilation is nearly exclusively performed by gut Bacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAA-treated mice revealed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activities of Bacteroides and Bifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability of Bacteroides and Bifidobacterium to metabolize dietary sphingolipids. We conclude that BOSSS provides a platform to study the flux of virtually any alkyne-labeled metabolite in diet–microbiome interactions.

The plasma membrane of neurons consists of distinct domains, each of which carries specialized functions and a characteristic set of membrane proteins. While this compartmentalized membrane organization is essential for neuronal functions, it remains controversial how neurons establish these domains on the laterally fluid membrane. Here, using immunostaining, lipid-MS analysis and gene ablation with the CRISPR/Cas9 system, we report that the pancreatic lipase-related protein 2 (PLRP2), a phospholipase A1 (PLA1), is a key organizer of membrane protein localization at the neurite tips of PC12 cells. PLRP2 produced local distribution of 1-oleoyl-2-palmitoyl-PC at these sites through acyl-chain remodeling of membrane phospholipids. The resulting lipid domain assembled the syntaxin 4 (Stx4) protein within itself by selectively interacting with the transmembrane domain of Stx4. The localized Stx4, in turn, facilitated the fusion of transport vesicles that contained the dopamine transporter with the domain of the plasma membrane, which led to the localized distribution of the transporter to that domain. These results revealed the pivotal roles of PLA1, specifically PLRP2, in the formation of functional domains in the plasma membrane of neurons. In addition, our results suggest a mode of membrane organization in which the local acyl-chain remodeling of membrane phospholipids controls the selective localization of membrane proteins by regulating both lipid-protein interactions and the fusion of transport vesicles to the lipid domain.

Ion mobility separates molecules in the gas-phase based on their physico-chemical properties, providing information about their size as collisional cross-sections. The timsTOF Pro combines trapped ion mobility with a quadrupole, collision cell and a TOF mass analyzer, to probe ions at high speeds with on-the-fly fragmentation. Here, we show that on this platform ion mobility is beneficial for cross-linking MS (XL-MS). Cross-linking reagents covalently link amino acids in proximity, resulting in peptide pairs after proteolytic digestion. These cross-linked peptides are typically present at low abundance in the background of normal peptides, which can partially be resolved by using enrichable cross-linking reagents. Even with a very efficient enrichable cross-linking reagent, like PhoX, the analysis of cross-linked peptides is still hampered by the co-enrichment of peptides connected to a partially hydrolyzed reagent – termed mono-linked peptides. For experiments aiming to uncover protein-protein interactions these are unwanted byproducts. Here, we demonstrate that gas-phase separation by ion mobility enables the separation of mono-linked peptides from cross-linked peptide pairs. A clear partition between these two classes is observed at a CCS of 500 Ų and a monoisotopic mass of 2 kDa, which can be used for targeted precursor selection. A total of 50-70% of the mono-linked peptides are prevented from sequencing, allowing the analysis to focus on sequencing the relevant cross-linked peptide pairs. In applications to both simple proteins and protein mixtures and a complete highly complex lysate this approach provides a substantial increase in detected cross-linked peptides.

A key point in achieving accurate intact glycopeptide identification is the definition of the glycan composition file that is used to match experimental with theoretical masses by a glycoproteomics search engine. At present, these files are mainly built from searching the literature and/or querying data sources focused on posttranslational modifications. Most glycoproteomics search engines include a default composition file that is readily used when processing MS data. We introduce here a glycan composition visualizing and comparative tool associated with the GlyConnect database and called GlyConnect Compozitor. It offers a web interface through which the database can be queried to bring out contextual information relative to a set of glycan compositions. The tool takes advantage of compositions being related to one another through shared monosaccharide counts and outputs interactive graphs summarizing information searched in the database. These results provide a guide for selecting or deselecting compositions in a file in order to reflect the context of a study as closely as possible. They also confirm the consistency of a set of compositions based on the content of the GlyConnect database. As part of the tool collection of the Glycomics@ExPASy initiative, Compozitor is hosted at https://glyconnect.expasy.org/compozitor/ where it can be run as a web application. It is also directly accessible from the GlyConnect database.

President-elect Donald Trump wants legal authorities to investigate what he said were possibly illegal rumors he is going to sell his majority stock stake in Trump Media. He claims he won't sell.

A 77-year-old slice of cake from Queen Elizabeth II's wedding to Prince Philip was auctioned for $2,800.

Individual interventions for burnout don’t work. Researchers explain why.

RUTHERFORD, N.J., Dec. 5, 2023 — Intelligent Light has announced it has been selected by AFWERX for a Direct-to-Phase II contract in the amount of $1.15 Million focused on IntelliTwin […]

The post AFWERX Selects IntelliTwin as the Realizable Digital Thread for HPC-scale CFD appeared first on HPCwire.

President-elect Donald Trump has chosen former Republican Rep. Lee Zeldin of New York to run the Environmental Protection Agency.

Struggling to be kind to yourself? Learn how to direct compassion inwards with these simple techniques.

Are you thinking about a career that really makes a difference? Consider counseling. It’s more than just a job; it’s a lifeline for many. Counselors dive into the world of human emotions and experiences, offering a guiding light to those navigating life’s complexities. This isn’t about having all the answers. It’s about listening, understanding, and […]

The post The Importance of Counseling as a Profession first appeared on What is Psychology?.

Millions of Americans suffer from depression, anxiety, and other mental health conditions. And yet, many do not even know about the countless self-care practices for maintaining mental health and wellbeing. We will uncover some of the most effective practices for dealing with these issues. Let’s jump right in. #1: Regular Physical Activity Exercise is a […]

The post Self-Care Practices for Maintaining Mental Health and Wellbeing first appeared on What is Psychology?.

Small groups of Portland youngsters gathered in gardens, played with plant-based dyes, and cooked up vegan meals as part of Camp ELSO's mission to foster STEM learning for students of color.

Thomas Jefferson High School for Science and Technology will see a new test-free admissions process by November, district leaders say.

The ability to discern fact from fiction and to recognize reliable news is fundamental, writes News Literacy Project’s Charles Salter.

Curtis Jones, a U.S. Army veteran who has led Georgia's Bibb County school system since 2015, has been named the 2019 AASA National Superintendent of the Year.

The College Football Playoff selection committee released its second top-25 rankings of the season ahead of the first 12-team playoff, and unsurprisingly, the Oregon Ducks are still the No. 1 team. Of course, there are still many game

Georgia football tumbled nine spots in the College Football Playoff rankings Tuesday and fell out of the 12-team bracket. What committee chair said

David Schuler, the superintendent of Township High School District 214 in Arlington Heights, Ill., has been named 2018 National Superintendent of the Year.