In SAS Merchandise Financial Planning, custom time frame-based data versions do not aggregate correctly when referenced in worksheets with standard hierarchy levels. The data does not aggregate correctly from l

The divalent anion sodium symporter (DASS) family (SLC13) plays critical roles in metabolic homeostasis, influencing many processes, including fatty acid synthesis, insulin resistance, and adiposity. DASS transporters catalyze the Na+-driven concentrative uptake of Krebs cycle intermediates and sulfate into cells; disrupting their function can protect against age-related metabolic diseases and can extend lifespan. An inward-facing crystal structure and an outward-facing model of a bacterial DASS family member, VcINDY from Vibrio cholerae, predict an elevator-like transport mechanism involving a large rigid body movement of the substrate-binding site. How substrate binding influences the conformational state of VcINDY is currently unknown. Here, we probe the interaction between substrate binding and protein conformation by monitoring substrate-induced solvent accessibility changes of broadly distributed positions in VcINDY using a site-specific alkylation strategy. Our findings reveal that accessibility to all positions tested is modulated by the presence of substrates, with the majority becoming less accessible in the presence of saturating concentrations of both Na+ and succinate. We also observe separable effects of Na+ and succinate binding at several positions suggesting distinct effects of the two substrates. Furthermore, accessibility changes to a solely succinate-sensitive position suggests that substrate binding is a low-affinity, ordered process. Mapping these accessibility changes onto the structures of VcINDY suggests that Na+ binding drives the transporter into an as-yet-unidentified conformational state, involving rearrangement of the substrate-binding site–associated re-entrant hairpin loops. These findings provide insight into the mechanism of VcINDY, which is currently the only structurally characterized representative of the entire DASS family.

Ion mobility brings an additional dimension of separation to LC–MS, improving identification of peptides and proteins in complex mixtures. A recently introduced timsTOF mass spectrometer (Bruker) couples trapped ion mobility separation to TOF mass analysis. With the parallel accumulation serial fragmentation (PASEF) method, the timsTOF platform achieves promising results, yet analysis of the data generated on this platform represents a major bottleneck. Currently, MaxQuant and PEAKS are most used to analyze these data. However, because of the high complexity of timsTOF PASEF data, both require substantial time to perform even standard tryptic searches. Advanced searches (e.g. with many variable modifications, semi- or non-enzymatic searches, or open searches for post-translational modification discovery) are practically impossible. We have extended our fast peptide identification tool MSFragger to support timsTOF PASEF data, and developed a label-free quantification tool, IonQuant, for fast and accurate 4-D feature extraction and quantification. Using a HeLa data set published by Meier et al. (2018), we demonstrate that MSFragger identifies significantly (~30%) more unique peptides than MaxQuant (1.6.10.43), and performs comparably or better than PEAKS X+ (~10% more peptides). IonQuant outperforms both in terms of number of quantified proteins while maintaining good quantification precision and accuracy. Runtime tests show that MSFragger and IonQuant can fully process a typical two-hour PASEF run in under 70 min on a typical desktop (6 CPU cores, 32 GB RAM), significantly faster than other tools. Finally, through semi-enzymatic searching, we significantly increase the number of identified peptides. Within these semi-tryptic identifications, we report evidence of gas-phase fragmentation before MS/MS analysis.

The neuronal basis of complex social behavior is still poorly understood. In honeybees, reproductive investment decisions are made at the colony-level. Queens develop from female-destined larvae that receive alloparental care from nurse bees in the form of ad-libitum royal jelly (RJ) secretions. Typically, the number of raised new queens is limited but genetic breeding of "royal jelly bees" (RJBs) for enhanced RJ production over decades has led to a dramatic increase of reproductive investment in queens. Here, we compare RJBs to unselected Italian bees (ITBs) to investigate how their cognitive processing of larval signals in the mushroom bodies (MBs) and antennal lobes (ALs) may contribute to their behavioral differences. A cross-fostering experiment confirms that the RJB syndrome is mainly due to a shift in nurse bee alloparental care behavior. Using olfactory conditioning of the proboscis extension reflex, we show that the RJB nurses spontaneously respond more often to larval odors compared with ITB nurses but their subsequent learning occurs at similar rates. These phenotypic findings are corroborated by our demonstration that the proteome of the brain, particularly of the ALs differs between RJBs and ITBs. Notably, in the ALs of RJB newly emerged bees and nurses compared with ITBs, processes of energy and nutrient metabolism, signal transduction are up-regulated, priming the ALs for receiving and processing the brood signals from the antennae. Moreover, highly abundant major royal jelly proteins and hexamerins in RJBs compared with ITBs during early life when the nervous system still develops suggest crucial new neurobiological roles for these well-characterized proteins. Altogether, our findings reveal that RJBs have evolved a strong olfactory response to larvae, enabled by numerous neurophysiological adaptations that increase the nurse bees' alloparental care behavior.

Mallory-Denk-bodies (MDBs) are hepatic protein aggregates associated with inflammation both clinically and in MDB-inducing models. Similar protein aggregation in neurodegenerative diseases also triggers inflammation and NF-B activation. However, the precise mechanism that links protein aggregation to NF-B-activation and inflammatory response remains unclear. Herein we find that treating primary hepatocytes with MDB-inducing agents (N-methylprotoporphyrin (NMPP), protoporphyrin IX (PPIX), or Zinc-protoporphyrin IX (ZnPP)) elicited an IBα-loss with consequent NF-B activation. Four known mechanisms of IBα-loss i.e. the canonical ubiquitin-dependent proteasomal degradation (UPD), autophagic-lysosomal degradation, calpain degradation and translational inhibition, were all probed and excluded. Immunofluorescence analyses of ZnPP-treated cells coupled with 8 M urea/CHAPS-extraction revealed that this IBα-loss was due to its sequestration along with IBβ into insoluble aggregates, thereby releasing NF-B. Through affinity pulldown, proximity biotinylation by antibody recognition, and other proteomic analyses, we verified that NF-B subunit p65, which stably interacts with IBα under normal conditions, no longer binds to it upon ZnPP-treatment. Additionally, we identified 10 proteins that interact with IBα under baseline conditions, aggregate upon ZnPP-treatment, and maintain the interaction with IBα after ZnPP-treatment, either by cosequestering into insoluble aggregates or through a different mechanism. Of these 10 proteins, the nucleoporins Nup153 and Nup358/RanBP2 were identified through RNA-interference, as mediators of IBα-nuclear import. The concurrent aggregation of IBα, NUP153, and RanBP2 upon ZnPP-treatment, synergistically precluded the nuclear entry of IBα and its consequent binding and termination of NF-B activation. This novel mechanism may account for the protein aggregate-induced inflammation observed in liver diseases, thus identifying novel targets for therapeutic intervention. Because of inherent commonalities this MDB cell model is a bona fide protoporphyric model, making these findings equally relevant to the liver inflammation associated with clinical protoporphyria.

Our weekly series previewing each of baseball's six divisions begins with the American League West. Let's take a team-by-team look at the biggest questions this season.

Russia’s aggression and a crisis for multilateralism 30 March 2023 — 1:00PM TO 2:00PM Anonymous (not verified) 23 March 2023 Chatham House and Online

In conversation with Dmytro Kuleba, minister of foreign affairs of Ukraine, about how multilateral organizations struggle to respond adequately to Russia’s full-scale invasion of Ukraine.

As a permanent member of the UN Security Council, Russia pursues this war in defiance of the umbrella organization’s multiple resolutions condemning the invasion, along with its war crimes, annexation of territory, deliberate targeting of civilian nuclear infrastructure, cultural extermination, and global disinformation campaign. 

This event explores the following questions: 

• How should the response of the UN to Russian aggression be assessed? 
• What can be done to uphold the guiding principles of the UN Charter? 
• Is there a ‘UN problem’ or a ‘Russia problem’? 
• How can trust and the legitimacy of multilateral cooperation be restored in times of strategic rivalry and rising global tensions?
• Who can drive such an effort? 
• Is post-Soviet transfer of the UN Security Council seat to Russia a cause of current impunity? 

This event features a live in-person audience in Kyiv as well as in London and online.

Ukraine crisis could trigger cascading risks globally Expert comment NCapeling 16 March 2022

The effects on the wider world from the Ukraine invasion go far beyond the waves of shock and horror being felt from this escalating conflict.

Russia and Ukraine rank 11th and 55th respectively in terms of their national economies but, for the global supply of critical resources such as energy, food, and minerals, these two countries together are far bigger hitters – and both the threat and reality of resource flows from them being reduced have already driven up global prices.

The world is already facing a cost-of-living squeeze coming out of the COVID-19 pandemic, so further price spikes or supply constraints have the potential to seriously undermine food and energy security, equitable access to basic goods and services, and social stability around the world – which can then potentially create systemic risks for economies and societies.

The global implications of the Ukraine conflict are only just beginning to be explored fully but the immediate impacts of the crisis on global markets are already well-documented. In the first few days after Russia’s invasion, energy prices spiked, triggering further fertilizer price rises – as fertilizer production is highly energy intensive – which in turn is contributing to food price rises because fertilizer costs are an important factor in food production.

Interruptions to shipping in the region around Ukraine – as well as globally – have impeded the flow of goods which pushed prices up even further, while economic sanctions on cross-border flows of goods and finance are further adding to market pressures. But this is just the start – these impacts will bring ripple effects which propagate far beyond their point of origin, known as ‘cascading risks’.

Risk is a combination of hazard, exposure, and vulnerability – in terms of the Ukraine invasion, the hazard is the conflict and its immediate impacts on the societies and economies of Ukraine and Russia, while exposure relates to the degree to which other countries are likely to be affected depending on how much they are integrated into the global economy or the ‘just in time’ nature of their supply chains.

Vulnerability relates to a society’s capacity to mitigate the harmful impacts of the conflict, such as controlling borders, sourcing alternative goods from suppliers, or protecting against price or supply shocks.

Risk cascades – the second- and third-order impacts of the original hazard and of responses to that hazard – can interact across sectoral boundaries – as with energy and food, for example – and their compound effect can lead to overall systemic risks for society.

Anticipating this potential is essential to understanding the nature and scale of the global ramifications being felt from the Ukraine conflict. Recent work in the UK to assess levels of cascading risks resulting from a changing climate – the UK Climate Change Risk Assessment – provides a valuable framework for thinking about this area.

It examines key pathways for risk to cascade through global systems – when applied to the situation in Ukraine, these pathways and their interactions offer an indication of the scale of crisis that citizens face far beyond Ukraine’s and Russia’s borders.

Interruptions to the flows of goods and energy

In globalized trade networks, localized disruption to supply chains rapidly yields widespread international impacts – of particular concern is the immediate supply of food because most countries rely on lean supply chains and some may only have a few days food within their own borders.

Experience from previous food price crises indicate even small interruptions to trade can result in runs on the market and rapid price inflation. In the case of this conflict, the trade interruption will be far from small because, between them, Russia and Ukraine export around one-quarter of all traded wheat, more than three-quarters of traded sunflower oil, and one-sixth of traded maize.

Energy markets are also a concern because many countries use more energy than they produce and therefore rely on imports of energy or fuel for domestic use. Russia produces around ten per cent of the world’s commercial energy with a concentration of sales in major regions such as the European Union (EU) and China.

As with food, a shortfall in energy provision leads to market runs and rapid inflation as actors compete in a tightening space, while poorly designed policy interventions by nations trying to ensure their own security add further pressure to global supply and worsen price rises. In addition, the closely interconnected nature of energy markets means disruption to one fuel – such as gas in this case – affects global prices for other forms of energy.

The impact of moving people and money

As the last decade richly illustrates, the cross-border flows of people impact those societies absorbing them – for example, contributing to a rise in nationalism – as well as increase the costs of supplying essential resources. Given many people are understandably fleeing this conflict, other countries may struggle to cope as the cost-of-living crisis and urgent efforts to bolster national security infrastructure may squeeze available public funds.

Financial flows are crucial to the functioning of global economies, whether for inward investment or insurance and – as Russian citizens may be about to discover – restricting the global flow of money has a serious impact on households. Beyond Russia, the outflow of money from major financial centres such as London to meet insurance claims or to enable infrastructure reinvestment post-conflict may also have severe knock-on economic impacts.

The impact on governance and health

The global spikes in energy and food prices resulting from these supply chain disruptions will see many countries struggle with rising food and energy insecurity as well as increased inequality. Taken together these conditions create many issues beyond immigration pressures and the associated politics, including increased inequality and civil unrest.

This potentially destabilizes governments which has consequences for the stability of an entire region such as interrupted supply chains, the need to deploy peacekeeping forces, or significant flows of aid – all with global consequences far beyond the countries in question.

Populations may suffer mental health impacts arising from the Ukraine invasion, whether from the trauma of being forced to leave home to escape conflict, anxiety for the wellbeing and safety of families and friends caught up in it, or a more general anxiety arising from the perception of living in an unstable world.

A British daredevil was intentionally dragged behind his motorcycle at a speed of 159.52 mph to break a Guinness World Record.

The 2024 Egg Fair in Mexico broke a Guinness World Record when more than 2,000 young people participated in a race while balancing eggs on spoons.

The Army has successfully tested the MK-22 Precision Sniper Rifle to clear it for fielding.

U.S. Defense Secretary Lloyd Austin said Ukraine continues to have U.S. support against Russian aggression and is free to decide its own foreign policy during a visit to Kyiv Tuesday. 

Researchers have a clearer picture than ever before of how common conditions that involve aggressive behavior emerge and how treatment can help

Nutritional supplements that contain curcumin -- a natural anti-inflammatory compound -- may protect the eyes from the development and progression of age-related macular degeneration, a new study suggests.

Virtual yoga can be a successful and accessible way to manage chronic low back pain -- a common ailment with major consequences, a new study suggests.

Quantum error correction specialist Riverlane today released a fascinating report — The Quantum Error Correction Report 2024 — that’s worth scanning; IBM and 28 collaborators last week released V-score, a […]

The post Quantum Nuggets: Riverlane’s 2024 QEC Study, IBM’s V-score, Twisted Semiconductors appeared first on HPCwire.

Film star Chris Pratt and his wife, author Katherine Schwarzenegger, have announced the birth of their third child.

In this ode to improvisation, musician and comedian Reggie Watts beatboxes, raps, loops his own rhythms and reflects upon the everyday power of turning the mundane into magic. After all, he says, we're all just making it up as we go along.

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.

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.

Pennsylvania Gov. Tom Wolf, a Democrat, has become increasingly critical of charter schools this year, and his new proposals for charters would change how they operate and how they are funded.

Schools are slowly figuring out how to balance thinking globally with acting locally, and recognizing that some key skills are valuable no matter where students end up living.

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.

Convinced that the show must go on, many high school theater troupes are turning to livestreamed productions, outdoor performances, and radio plays.

The Christie administration is arguing that the only way to improve education in the state's poorest districts is to ditch teacher job protections.

Emotions remain raw as educators and residents in a rural Wisconsin district dig for solutions after being denied the option of dissolving.

Schools are slowly figuring out how to balance thinking globally with acting locally, and recognizing that some key skills are valuable no matter where students end up living.

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.

The study found that youth in rural New Hampshire have poor perceptions of job opportunities in the area, and are more likely to be depressed or abuse substances than other rural youth.

Mississippi, Arkansas, and New Mexico have the highest percentages of students who lack adequate home technology for remote learning.

Confusion reigns when it comes to finding and reporting data on school-related coronavirus infections. That's a problem for school leaders weighing shutdowns.

A Greenville, Miss. teacher was fired and a superintendent placed on administrative leave after a video of a student being dragged by her hair surfaced on social media.

Confusion reigns when it comes to finding and reporting data on school-related coronavirus infections. That's a problem for school leaders weighing shutdowns.

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease

Aggression involves both sexually monomorphic and dimorphic actions. How the brain implements these two types of actions is poorly understood. We found that in Drosophila melanogaster, a set of neurons, which we call CL062, previously shown to mediate male aggression also mediate female aggression. These neurons elicit aggression acutely and without the presence of a target. Although the same set of actions is elicited in males and females, the overall behavior is sexually dimorphic. The CL062 neurons do not express fruitless, a gene required for sexual dimorphism in flies, and expressed by most other neurons important for controlling fly aggression. Connectomic analysis in a female electron microscopy dataset suggests that these neurons have limited connections with fruitless expressing neurons that have been shown to be important for aggression and signal to different descending neurons. Thus, CL062 is part of a monomorphic circuit for aggression that functions parallel to the known dimorphic circuits.

A chick in the process of hatching as the female adult looks on

The newly discovered Lllacme plenipes has up to 750 legs, more than any other known creature

Videos from the 1950s show architect Frank Lloyd Wright at the site of the Guggenheim Museum

New DNA analysis adds to growing research indicating the famous Pacific island did not collapse from overuse of resources before the arrival of Europeans