The LDL receptor-related protein-1 (LRP1) is highly expressed in numerous cell types, and its impairment is associated with obesity, diabetes, and fatty liver disease. However, the mechanisms linking LRP1 to metabolic disease are not completely understood. Here, we compared the metabolic phenotype of C57BL/6J wild type and LRP1 knock-in mice carrying an inactivating mutation in the distal NPxY motif after feeding a low fat (LF) diet or high fat diets with (HFHC) or without (HF) cholesterol supplementation. In response to HF feeding, both groups developed hyperglycemia, hyperinsulinemia, and hyperlipidemia, as well as increased adiposity with adipose tissue inflammation and liver steatosis. However, when animals were fed the HF diet supplemented with cholesterol, the LRP1 NPxY mutation prevents hypercholesterolemia, reduces adipose tissue and brain inflammation, and limits liver progression to steatohepatitis. Nevertheless, insulin signaling is impaired in LRP1 NPxY mutant hepatocytes and this mutation does not protect against HFHC-induced insulin resistance. The selective metabolic improvement observed in HFHC-fed LRP1 NPxY mutant mice is due to an apparent increase of hepatic LDL receptor levels, leading to an elevated rate of plasma lipoprotein clearance and lowering of plasma and hepatic cholesterol levels. The unique metabolic phenotypes displayed by LRP1 NPxY mutant mice in response to HF or HFHC diet feeding indicate an LRP1-cholesterol axis in modulating tissue inflammation. The LRP1 NPxY mutant mouse phenotype differs from phenotypes observed in mice with tissue-specific LRP1 inactivation, thus highlighting the importance of an integrative approach to evaluate how global LRP1 dysfunction contributes to metabolic disease development.

Influenza A virus (IAV) mutates rapidly, resulting in antigenic drift and poor year-to-year vaccine effectiveness. One challenge in designing effective vaccines is that genetic mutations frequently cause amino acid variations in IAV envelope protein hemagglutinin (HA) that create new N-glycosylation sequons; resulting N-glycans cause antigenic shielding, allowing viral escape from adaptive immune responses. Vaccine candidate strain selection currently involves correlating antigenicity with HA protein sequence among circulating strains, but quantitative comparison of site-specific glycosylation information may likely improve the ability to design vaccines with broader effectiveness against evolving strains. However, there is poor understanding of the influence of glycosylation on immunodominance, antigenicity, and immunogenicity of HA, and there are no well-tested methods for comparing glycosylation similarity among virus samples. Here, we present a method for statistically rigorous quantification of similarity between two related virus strains that considers the presence and abundance of glycopeptide glycoforms. We demonstrate the strength of our approach by determining that there was a quantifiable difference in glycosylation at the protein level between WT IAV HA from A/Switzerland/9715293/2013 (SWZ13) and a mutant strain of SWZ13, even though no N-glycosylation sequons were changed. We determined site-specifically that WT and mutant HA have varying similarity at the glycosylation sites of the head domain, reflecting competing pressures to evade host immune response while retaining viral fitness. To our knowledge, our results are the first to quantify changes in glycosylation state that occur in related proteins of considerable glycan heterogeneity. Our results provide a method for understanding how changes in glycosylation state are correlated with variations in protein sequence, which is necessary for improving IAV vaccine strain selection. Understanding glycosylation will be especially important as we find new expression vectors for vaccine production, as glycosylation state depends greatly on the host species.

Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.

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.

We have previously shown that multimers of plasma pentraxin-3 (PTX3) were predictive of survival in patients with sepsis. To characterize the release kinetics and cellular source of plasma protein changes in sepsis, serial samples were obtained from healthy volunteers (n=10, 3 time-points) injected with low-dose endotoxin (LPS) and analyzed using data-independent acquisition (DIA) MS. The human plasma proteome response was compared to an LPS-induced endotoxemia model in mice. Proteomic analysis of human plasma revealed a rapid neutrophil degranulation signature, followed by a rise in acute phase proteins. Changes in circulating PTX3 correlated with increases in neutrophil-derived proteins following LPS injection. Time course analysis of the plasma proteome in mice showed a time-dependent increase in multimeric PTX3, alongside increases in neutrophil-derived myeloperoxidase (MPO) upon LPS treatment. The mechanisms of oxidation-induced multimerisation of PTX3 were explored in two genetic mouse models: MPO global knock-out mice and LysM CreNox2KO mice, in which NADPH oxidase 2 (Nox2) is only deficient in myeloid cells. Nox2 is the enzyme responsible for the oxidative burst in neutrophils. Increases in plasma multimeric PTX3 were not significantly different between wildtype and MPO or LysM CreNox2KO knock-out mice. Thus, PTX3 may already be stored and released in a multimeric form. Through in vivo neutrophil depletion and multiplexed vascular proteomics, PTX3 multimer deposition within the aorta was confirmed to be neutrophil-dependent. Proteomic analysis of aortas from LPS-injected mice returned PTX3 as the most upregulated protein, where multimeric PTX3 was deposited as early as 2 h post-LPS along with other neutrophil-derived proteins. In conclusion, the rise in multimeric PTX3 upon LPS injection correlates with neutrophil-related protein changes in plasma and in aortas. MPO and myeloid Nox2 are not required for the multimerisation of PTX3; instead, neutrophil extravasation is responsible for the LPS-induced deposition of multimeric PTX3 in the aorta.

How Influential Is China in Zimbabwe? Expert comment sysadmin 20 November 2017

A trip to Beijing by Zimbabwe’s military chief was a ‘normal military exchange’, China’s foreign ministry said after the army seized power in Harare. Alex Vines examines the extent of China’s influence in Zimbabwe.

The news that General Constantino Chiwenga had visited China only a few days before the military takeover in Zimbabwe was a coincidence that did not go unnoticed. There was also speculation after China said it was closely watching developments, but stopped short of condemning President Robert Mugabe’s apparent removal from power.

China is Zimbabwe’s fourth-largest trading partner and its largest source of investment - with stakes worth many billions of pounds in everything from agriculture to construction. Zimbabwe is the dependent partner - with China providing the largest market for its exports and much needed support to its fragile economy.

China’s relations with Zimbabwe are deep, starting during the Rhodesian Bush War. Robert Mugabe failed in 1979 to get Soviet backing, so turned to China, which provided his guerrilla fighters with weapons and training. Both countries formally established diplomatic relations at Zimbabwean independence in 1980 and Mugabe visited Beijing as prime minister the following year. He has been a regular visitor since.

For years, Zimbabwe’s officials have tried to play off China against the West, advocating the country’s ‘Look East’ strategy, particularly following the introduction of EU sanctions in 2002. Indeed, a decade ago, Mugabe told a packed rally at the Chinese-built national sports stadium in Harare: ‘We have turned east, where the sun rises, and given our back to the west, where the sun sets.’

China’s military engagement also deepened during Zimbabwe’s ‘Look East’ era. Significant purchases were made, including Hongdu JL-8 jet aircraft, JF-17 Thunder fighter aircraft, vehicles, radar and weapons. However, following a controversy about a shipment of arms in 2008, Beijing decided to list Zimbabwe for ‘limited level’ military trading.

Despite Zimbabwe’s efforts, the ‘Look East’ strategy did not bring the investment flood hoped for and a decade later, in August 2015, Mugabe openly asked for Western re-engagement in his ‘state of the nation’ address.

Now, the reality is that increasingly Chinese and Western interests - particularly those of the UK - have become aligned. Not far from each other in the outer suburbs of Harare, two of the biggest embassies in Zimbabwe are the British and the Chinese. As other embassies scaled down or closed, Beijing’s expanded. Whereas British diplomats were well connected with business, civil society and opposition figures, the Chinese invested in ‘technical support’ of the party of government Zanu-PF, including state security and the presidency. When it came to Zanu-PF politics and factionalism, Chinese diplomats were well connected and insightful and, like their Western colleagues, concerned about stability, a better investment climate and adherence to the rule of law.

President Xi Jinping visited Zimbabwe in 2015 and President Mugabe visited Beijing in January 2017. In public, the Chinese leader said his country is willing to encourage capable companies to invest in Zimbabwe. But in private, the message was that there would be no more loans until Zimbabwe stabilized its economy.

In 2016 trade between the two countries amounted to $1.1 billion, with China the biggest buyer of Zimbabwean tobacco and also importing cotton and various minerals. In return Zimbabwe imported electronics, clothing and other finished products. Chinese state construction firms have also been active, building infrastructure including Zimbabwe’s $100 million National Defence College. And last year China agreed to finance a new 650-seat parliament in Harare.

But Chinese diplomats and many businesses are waiting for better days in Zimbabwe. Some companies have found the investment climate challenging - being burned on diamonds, for example - and have looked for alternative markets. A couple of weeks ago I was in China, attending a meeting on China-Africa relations and Zimbabwe was not mentioned once. Unlike Ethiopia, Sudan, or Angola that are strategic partners, or big markets like Nigeria, Kenya and South Africa, Zimbabwe is far from being Beijing’s new priority.

So, Beijing’s interest is in a better investment climate in Zimbabwe. A clear transitional arrangement resulting in elections for a legitimate government in Harare is as much in Beijing’s interest as London’s.

The ‘Look East’ and the ‘Re-engagement with the West’ strategies have not brought about the confidence and investment that Zimbabwe needs. What Zimbabwe requires is stable and accountable government - then investors from Asia, America and Europe will seriously consider that Zimbabwe has an investment future. This was the message that Mugabe received in Beijing in January. And the one which Zimbabwe’s military chief also was given last week.

This article was originally published by BBC News.

Mine Action in Angola: Clearing the Legacies of Conflict to Harness the Potential of Peace Other resource sysadmin 14 June 2019

This publication draws on and updates the briefing note published following a meeting of the All- Party Parliamentary Group (APPG) on Angola on 26 April 2017. It also incorporates insights from a Chatham House Africa Programme conference session on the legacies of the Angolan Civil War, held on 23 March 2018; and draws on the Africa Programme’s research into conservation-driven development models in Southern Africa.

Almost two decades after the end of its civil war, Angola remains one of the most heavily landmine-contaminated countries in the world. The Angolan government has committed to clearing its landmines by 2025, and there is constructive collaboration between the government and mine clearing agencies in this endeavour, but the target will be achievable only if a decline in funding from international donors is reversed. International funding for mine clearance in Angola fell by more than 80 per cent between 2005 and 2017, and this sharp drop in external support has compounded the impact on domestic funding for national clearance efforts as a result of the downturn in prices for Angola’s main export commodities.

The national mine action agency, the Comissão Nacional Intersectorial de Desminagem e Assistência Humanitária (CNIDAH), is supported by the Mines Advisory Group (MAG), Norwegian People’s Aid (NPA) and the HALO Trust. By 2017, 15 years after the end of the civil war, these organizations had collectively helped clear 56 per cent of known landmine-contaminated land. State-led demining has focused principally on clearing areas designated for infrastructure projects. Now, it is critical that humanitarian demining in largely agricultural and conservation areas is prioritized to bring to an end the daily threat to Angola’s rural poor – as well as to the country’s livestock and wildlife – of injury or death as a result of landmine accidents.

Angola has some of the world’s most important remaining wilderness, including the tributary system for the unique Okavango Delta, and the country has the potential to host one of the most diverse wildlife populations on the continent. However, the presence of landmines and other remnants of the civil war render large areas of the country unsafe both for wildlife and for the local people, whose ability to derive a sustainable livelihood from their natural environment is fundamental to its protection.

Wildlife and tourism provide important economic opportunities for diversification beyond an oil-dominated economy. Critically, Angola’s economic diversification and development objectives can only be achieved if the landmines that prohibit access to land for agriculture, mining, tourism and wildlife are cleared.

There are economic opportunities for released land in the most heavily mined provinces of Cuando Cubango and Moxico. Already, some new funding for mine action in Angola, if upscaled or matched by international donors, could be transformative for its people, and for the conservation of the region’s vital biodiversity.

Inclusion, agency and influence: The role of women in Zimbabwe’s economy 8 July 2021 — 3:00PM TO 4:30PM Anonymous (not verified) 2 July 2021 Online

Speakers discuss the changing role of women in Zimbabwe’s economic structures and the priorities for promoting greater economic inclusion, agency and influence of women.

Zimbabwe’s National Development Strategy of 2021-2025 highlights the importance of gender sensitivity in policymaking and of women’s economic participation in attaining the government’s Vision 2030.

However, women have been among the worst affected groups by the devastating effects that COVID-19 has had on Zimbabwe’s already floundering economy, which has exacerbated the challenges they face in economic life, such as access to credit, financial services and social security.

Leveraging existing structures such as women’s groups, micro-finance facilities, education and training, and national gender mechanisms, as well as supporting wider financial and digital inclusion in Zimbabwe, is central for the country’s sustained economic recovery.

This event also focuses on the differing impacts of COVID-19 on women’s economic activities across various sectors, as well as along rural-urban and formal-informal economy lines.

Read a meeting summary

This webinar is part of a series of events in partnership with the Konrad Adenauer Stiftung on Zimbabwe’s economic recovery and reform.

This event will also be broadcast live on the Africa Programme Facebook page.

Ten conflicts to watch in 2023 11 January 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 8 December 2022 Chatham House and Online

This event examines the most dangerous wars and crises through the lens of the International Crisis Group’s flagship annual report ‘10 Conflicts to watch in 2023’.

Each year, International Crisis Group compiles a list of the ten conflicts to watch that examines key conflicts across the globe. Please join us for this event at which Dr Comfort Ero, International Crisis Group president and CEO, discusses today’s and tomorrow’s most impactful wars and crises.

Key questions to consider include:

• What far-reaching repercussions and knock-on effects of Russia’s war on Ukraine will have for Europe and the rest of the world?

• Which crises beyond Ukraine warrant collective attention in the year ahead?

• How do rising tensions among major powers impact multilateral efforts to resolve these conflicts, impede progress on global challenges and impact institutions working on crisis prevention?

As with all members events, questions from the audience drive the conversation.

Read the transcript. 

Why a no-fly zone risks escalating the Ukraine conflict Expert comment NCapeling 13 March 2022

The US rejection of Poland’s offer to send fighter jets as a boost to Ukraine’s air defence shows just how uneasy nations are about direct combat with Russia.

The Pentagon’s decision to turn down the proposal by its fellow NATO member Poland to put Russian-made MiG-29 jets at its disposal demonstrates again how keen the US and allies are to avoid risking major confrontation with Russian forces.

The US Department of Defense says the offer to locate jets at bases in Germany was ‘not tenable’ as this risks flying into contested airspace over Ukraine – a non-NATO member – raising ‘serious concerns for the entire NATO alliance’ and echoing the continuing rejection of calls to implement no-fly zones (NFZs) as a way of easing the devastation being faced by trapped Ukraine civilians.

NFZs restrict any aircraft, including drones, from flying over a pre-defined region and can be used for both military and civilian purposes. But the implementation of NFZs is difficult to enforce and – most significantly – is unlikely to achieve the intended effect on the ground.

In conflict situations, they are usually implemented under the remit of United Nations (UN) peace support operations, requiring authorization under Article 42 of the UN Charter. This details that if all possible methods have proven ineffective in responding to a threat, countries ‘may take such action by air, or land forces as may be necessary to maintain or restore international peace and security’.

Protection but with limitations

NFZs provide both protection from attack and surveillance but do have limitations. They must be monitored and enforced which requires committing to fighter jet patrols with the explicit task of defending the area from the air by whatever means necessary.

This could mean jets firing upon Russian planes and drones so, if NATO allies and partners were to enforce a NFZ, it would represent an escalation of measures which is a step that would most likely provoke an unpredictable Vladimir Putin into further escalation – in short, it is highly likely to be seen as an act of war.

UK defence secretary Ben Wallace – among others – has repeatedly dispelled the idea, saying that enforcing NFZs would mean deploying ‘British fighter jets directly against Russian fighter jets’. In relation to moves such as the Polish jets, the Kremlin has warned that any countries offering airfields to Ukraine for attacks on Russia may be viewed as having entered the conflict.

There have only been three past instances of military NFZs. In Bosnia, as part of Operation Deny Flight from 1993-1995, a NFZ was enforced as part of a strategy which also including the provision of close air support and approved air strikes.

In Iraq, an NFZ endured for 12 years from 1991 and was succcesful in preventing Saddam Hussein from attacking Kurdish and Shia Muslim civilians. And in Libya in 2011, a NFZ was deployed to prevent the destruction of military infrastructure and the Libyan regime – although this quickly morphed into the provision of close air support.

So it is unclear just how successful NFZs are at providing protection. In Iraq and Libya, NFZ cover protection was provided but neither Saddam Hussein or Colonel Gaddafi were able to effectively target victims through their ground forces whereas, in Bosnia, Slobodan Milosevic infamously used ground troops to slaughter 8,000 Bosnian men and boys at Srebrenica.

Putin would still be able to continue to use both ground forces and artillery to assault Ukrainian cities with or without a NFZ – in fact, his sparse use of his Russian Aerospace Forces (VKS) has been one of the surprising features of the war so far. Under a NFZ, missile attacks could also continue, there is nothing in the record of no-fly zones to suggest the provision of safe areas for non-combatants would work.

And NFZs have only been successful against vastly inferior forces such as in Iraq, Bosnia, and Libya. But Russia has an air force second only in size to the US and has a vast range of defences including the potent S-400 Triumf at its disposal. Not only would an NFZ be ineffective, it might also not be possible to enforce without risking significant losses to the peace operations force.

It is due to a combination of these reasons that NFZs have not been used more in previous conflicts. The most recent consideration for a NFZ was in Syria but President Bashar al-Assad’s Syrian forces, protected by Russian air cover, could still have targeted their intended victims despite air policing so a NFZ was not used.

In the long-term, under the terms of a ceasefire agreement, it may be possible to include a NFZ under a UN or joint OSCE-UN peace terms. However, the forces involved should exclude NATO allies and partners or any states with Russian alliances to avoid further conflict.

This leaves few suitable countries with the capacity, willingness, and political stance to be called on. Two of the world’s most militarily capable states – China and India – abstained in the Uniting for Peace vote in the UN General Assembly (UNGA). Whether another willing state with the military capability – such as a Gulf state – could be considered acceptable to all sides remains to be tested.

Notable successes with SAMs

Many military commentators also note that currently Ukrainian forces are having notable success without jets, downing Russian aircraft using sophisticated surface-to-air missiles (SAMs) such as Stinger and Javelin, and NATO countries continue to supply those in their thousands.

War on Ukraine: Exploring the humanitarian response to the conflict 12 April 2022 — 12:00PM TO 1:00PM Anonymous (not verified) 6 April 2022 Online

This event explores the implications of the humanitarian realities from Russia’s invasion of Ukraine, the largest ground campaign in Europe since World War Two.

Reports from humanitarian organizations working in Ukraine are dire and reveal that a humanitarian disaster on an epic scale is unfolding.

The United Nations (UN) and other organizations estimate 12 million of Ukraine’s population are in need of assistance, 4.1 million have been displaced to neighbouring countries, and 6.4 million have become internally displaced.

Gillian Triggs, the assistant secretary-general and assistant high commissioner for protection at the UNHCR, joins other experts to discuss the humanitarian situation in Ukraine.

The panel considers:

• What are the greatest needs in Ukraine now?
• How can aid agencies meet those needs?
• What are the short and long-term implications of the crisis for Ukraine and Europe?
• How do international organizations work with local NGOs to provide food, medical aid and shelter?

This event is part of a regular series of events offering insight and analysis from experts and policymakers on how the war is affecting Ukraine, the region and the world.

This event is part of Chatham House’s ongoing work on the future of conflict.

Read the transcript

New research on 21st-century conflict 25 April 2022 — 5:00PM TO 6:00PM Anonymous (not verified) 11 April 2022 Online

This International Affairs webinar shares research on US special operations, urban warfare, and digital activism in recent conflicts.

Given the ongoing Russian invasion of Ukraine, and continuing conflicts in Myanmar, Yemen, and other countries, it is important to understand the changing nature of conflict in the 21st century.

In this webinar, authors from the March 2022 issue of International Affairs share research on the transformation of Western special forces, the impact of army size in urban warfare, and the use of social media and online activism in war.

The speakers in this event drew on the following research:

• US Special Forces transformation: post-Fordism and the limits of networked warfare (https://doi.org/10.1093/ia/iiab213)
• Urban insurgency in the twenty-first century: smaller militaries and increased conflict in cities (https://doi.org/10.1093/ia/iiac007)
• Diasporas as cyberwarriors: infopolitics, participatory warfare and the 2020 Karabakh war (https://doi.org/10.1093/ia/iiac015)

International Affairs was started at Chatham House in 1922 to communicate research to members who could not attend in person. Over the past 100 years, it has transformed into a journal that publishes academically rigorous and policy-relevant research. It is published for Chatham House by Oxford University Press. Read the latest issue here.

This analysis aimed to identify clinical factors associated with positivity on repeat ⁶⁸Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 ⁶⁸Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann–Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2–1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9–3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative ⁶⁸Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat ⁶⁸Ga-PSMA-11 PET/CT.

All-Pro left tackle Tristan Wirfs and tight ends Sam LaPorta and Dalton Kincaid were among key players injured in Week 10 of the NFL season.

In this era, expansion in digital infrastructure capacity is inevitable. Parallel to this, climate change consciousness is also rising, making sustainability a mandatory part of the organization’s functioning. As computing […]

The post Why IT Must Have an Influential Role in Strategic Decisions About Sustainability appeared first on HPCwire.

Discrimination -- prejudiced actions toward people based on their identity -- may cause stress that impairs gut health and lead to the growth of unhealthy bacteria that promote inflammation, a new study has found.

Many people overthink persuasion, when it is the most natural approaches that work best.

Roger Dooley's Brainfluence has been translated into eleven languages, but the new Spanish reading is the first audio audio translation.

The post Spanish Audiobook for Brainfluence appeared first on Neuromarketing.

Attendance and login records show that Ohio's Electronic Classroom of Tomorrow was paid for 9,000 students more than it should have been, according to a state audit.

With coronavirus cases surging, labor groups are continuing to flex their political muscle, most often pushing for a conservative approach to getting teachers and kids back in buildings.

Federal watchdogs find that Utah inflated its high school graduation rate in the last of a series of reports warning states not to make end runs around the rules for calculating graduation rates.

Prithviraj Rajebhosale
Oct 23, 2024; 44:e0063242024-e0063242024
Cellular

As evidence mounts that the cardiac-sympathetic nervous system reacts to challenging cognitive settings, we ask if these responses are epiphenomenal companions or if there is evidence suggesting a more intertwined role of this system with cognitive function. Healthy male and female human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous electroencephalographic and cardiac-sympathetic signals. Participants were reward sensitive but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters suggested that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics were consistent with widening decision boundaries serving to combat reward sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically mediated positive inotropy). We also saw evidence of conflict-specific "collaboration" between the neural and cardiac-sympathetic signals. In states of high conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signal's singular association. Cross-trial coherence analyses provided additional evidence that the autonomic systems controlling cardiac-sympathetics might influence the assessment of information streams during conflict by disrupting or overriding reward processing. We conclude that cardiac-sympathetic control might play a critical role, in collaboration with cognitive processes, during the approach-avoidance conflict in humans.

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by -secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V₃₂₁L) in the Nrg1 transmembrane domain that disrupts nuclear back signaling with minimal effects on forward signaling or local back signaling and was previously found to be associated with psychosis (Walss-Bass et al., 2006). We combined RNA sequencing, retroviral fate mapping of neural stem cells, behavioral analyses, and various network analyses of transcriptomic data to investigate the effect of disrupting Nrg1 nuclear back signaling in the dentate gyrus (DG) of male and female mice. The V₃₂₁L mutation impairs nuclear translocation of the Nrg1 ICD and alters gene expression in the DG. V₃₂₁L mice show reduced stem cell proliferation, altered cell cycle dynamics, fate specification defects, and dendritic dysmorphogenesis. Orthologs of known schizophrenia (SCZ)-susceptibility genes were dysregulated in the V₃₂₁L DG. These genes coordinated a larger network with other dysregulated genes. Weighted gene correlation network analysis and protein interaction network analyses revealed striking similarity between DG transcriptomes of V₃₂₁L mouse and humans with SCZ.

Neuroinflammation can positively influence axon regeneration following injury in the central nervous system. Inflammation promotes the release of neurotrophic molecules and stimulates intrinsic proregenerative molecular machinery in neurons, but the detailed mechanisms driving this effect are not fully understood. We evaluated how microRNAs are regulated in retinal neurons in response to intraocular inflammation to identify their potential role in axon regeneration. We found that miR-383-5p is downregulated in retinal ganglion cells in response to zymosan-induced intraocular inflammation. MiR-383-5p downregulation in neurons is sufficient to promote axon growth in vitro, and the intravitreal injection of a miR-383-5p inhibitor into the eye promotes axon regeneration following optic nerve crush. MiR-383-5p directly targets ciliary neurotrophic factor (CNTF) receptor components, and miR-383-5p inhibition sensitizes adult retinal neurons to the outgrowth-promoting effects of CNTF. Interestingly, we also demonstrate that CNTF treatment is sufficient to reduce miR-383-5p levels in neurons, constituting a positive-feedback module, whereby initial CNTF treatment reduces miR-383-5p levels, which then disinhibits CNTF receptor components to sensitize neurons to the ligand. Additionally, miR-383-5p inhibition derepresses the mitochondrial antioxidant protein peroxiredoxin-3 (PRDX3) which was required for the proregenerative effects associated with miR-383-5p loss-of-function in vitro. We have thus identified a positive-feedback mechanism that facilitates neuronal CNTF sensitivity in neurons and a new molecular signaling module that promotes inflammation-induced axon regeneration.

New York- FAO Director-General José Graziano da Silva and the President of the UN Security Council (UNSC), Ambassador Ismael Gaspar Martins, have concurred upon the importance of using FAO’s regular [...]

FAO Director-General José Graziano da Silva has been selected as one of the world's most influential Latin Americans for his work against hunger and malnutrition in the world. In its [...]

by Qu Dongyu, Director-General of the Food and Agriculture Organization of the United Nations (FAO).

Information Note.

Experts are working on a unique experiment that will use an inflatable aeroshell/heat shield to protect a spacecraft when entering a planet's atmosphere or returning to Earth

Thousands of years ago, our ancestors used symbols to track the sale of textile and agricultural products. New research suggests that these markings informed the development of writing

Quebec provincial police have confirmed that the body found in a Montreal nature park on Oct. 30 was that of kidnapping victim and cryptocurrency influencer Kevin Mirshahi.

Interim PC Leader Glen Savoie urged members to find a common purpose rather than blame former leader Blaine Higgs.

On Day 3 of TeenStreet there were separate meetings for girls and boys in the Main Hall. The theme of the day was 'influence', and the key verse of the day is found in Proverbs 4:23.

There might be a need for an economic theory to accurately forecast inflation.

The rise in prices under the Biden administration proved fatal for Kamala Harris’s election hopes.

A report of results: OM has been supporting church planting efforts and training local missionary teams to plant churches nearby and within the conflict area.

OM Ukraine and experts in crisis management held a seminar for pastors serving on both sides of the conflict line in Eastern Ukraine.

The former teacher, principal, and school superintendent became one of the most influential members of Congress on education policy during his 13 terms in the House.

Education Week reporters Alyson Klein and Sean Cavanagh discuss the races to watch.

The effectiveness of national voluntary programs asking companies to pledge to lower their pollution and greenhouse gas emissions depends on pressure from the public, according to a new study led by a Penn State researcher.

New findings from long-term research underscore the challenges managers face when trying to conserve Penn’s Woods. The seven-year study, conducted by a team of researchers from Penn State, the Pennsylvania Game Commission and Pennsylvania Department of Conservation and Natural Resources is the first to simultaneously assess how deer browsing, soil nutrients and competing vegetation affect tree regeneration in Keystone State forests.

Laura Pulido, Collins Chair and professor of Indigenous, race, and ethnic studies and geography at the University of Oregon, is the featured speaker for the College of Earth and Mineral Sciences’ 2024 EMS Reads program. She will give the keynote lecture at 6 p.m. on Wednesday Nov. 13, in Paterno Library's Foster Auditorium on Penn State's University Park campus.

There was positive rental growth in all provinces despite tenants feeling the pinch due to challenging economic conditions, according to the latest Payprop Rental Index.

Shares of Bidcorp, the food services giant founded by Brian Joffe, jumped almost 5% on Tuesday after it reported a record revenue performance for the four months to end October, including an "excellent" result from SA.

Argentine inflation has dipped to 193%, landing below the 200% threshold for the first time in close to a year, data from statistics agency INDEC showed on Tuesday, as President Javier Milei's dramatic austerity agenda bears fruit.

Donald Trump's impending White House return poses questions once again about conflicts of interest related to his business empire, with new cryptocurrency and other ventures raising fresh concerns.

Before deactivating her account, Imsha Rehman talked about dealing with negative comments, according to local media. She called the backlash "overwhelming".