Neurodegeneration in Parkinson's disease (PD) can be recapitulated in animals by administration of α-synuclein preformed fibrils (PFFs) into the brain. However, the mechanism by which these PFFs induce toxicity is unknown. Iron is implicated in PD pathophysiology, so we investigated whether α-synuclein PFFs induce ferroptosis, an iron-dependent cell death pathway. A range of ferroptosis inhibitors were added to a striatal neuron-derived cell line (STHdhQ7/7 cells), a dopaminergic neuron–derived cell line (SN4741 cells), and WT primary cortical neurons, all of which had been intoxicated with α-synuclein PFFs. Viability was not recovered by these inhibitors except for liproxstatin-1, a best-in-class ferroptosis inhibitor, when used at high doses. High-dose liproxstatin-1 visibly enlarged the area of a cell that contained acidic vesicles and elevated the expression of several proteins associated with the autophagy-lysosomal pathway similarly to the known lysosomal inhibitors, chloroquine and bafilomycin A1. Consistent with high-dose liproxstatin-1 protecting via a lysosomal mechanism, we further de-monstrated that loss of viability induced by α-synuclein PFFs was attenuated by chloroquine and bafilomycin A1 as well as the lysosomal cysteine protease inhibitors, leupeptin, E-64D, and Ca-074-Me, but not other autophagy or lysosomal enzyme inhibitors. We confirmed using immunofluorescence microscopy that heparin prevented uptake of α-synuclein PFFs into cells but that chloroquine did not stop α-synuclein uptake into lysosomes despite impairing lysosomal function and inhibiting α-synuclein toxicity. Together, these data suggested that α-synuclein PFFs are toxic in functional lysosomes in vitro. Therapeutic strategies that prevent α-synuclein fibril uptake into lysosomes may be of benefit in PD.

Type I and III interferons induce expression of the “myxovirus resistance proteins” MxA in human cells and its ortholog Mx1 in murine cells. Human MxA forms cytoplasmic structures, whereas murine Mx1 forms nuclear bodies. Whereas both HuMxA and MuMx1 are antiviral toward influenza A virus (FLUAV) (an orthomyxovirus), only HuMxA is considered antiviral toward vesicular stomatitis virus (VSV) (a rhabdovirus). We previously reported that the cytoplasmic human GFP-MxA structures were phase-separated membraneless organelles (“biomolecular condensates”). In the present study, we investigated whether nuclear murine Mx1 structures might also represent phase-separated biomolecular condensates. The transient expression of murine GFP-Mx1 in human Huh7 hepatoma, human Mich-2H6 melanoma, and murine NIH 3T3 cells led to the appearance of Mx1 nuclear bodies. These GFP-MuMx1 nuclear bodies were rapidly disassembled by exposing cells to 1,6-hexanediol (5%, w/v), or to hypotonic buffer (40–50 mosm), consistent with properties of membraneless phase-separated condensates. Fluorescence recovery after photobleaching (FRAP) assays revealed that the GFP-MuMx1 nuclear bodies upon photobleaching showed a slow partial recovery (mobile fraction: ∼18%) suggestive of a gel-like consistency. Surprisingly, expression of GFP-MuMx1 in Huh7 cells also led to the appearance of GFP-MuMx1 in 20–30% of transfected cells in a novel cytoplasmic giantin-based intermediate filament meshwork and in cytoplasmic bodies. Remarkably, Huh7 cells with cytoplasmic murine GFP-MuMx1 filaments, but not those with only nuclear bodies, showed antiviral activity toward VSV. Thus, GFP-MuMx1 nuclear bodies comprised phase-separated condensates. Unexpectedly, GFP-MuMx1 in Huh7 cells also associated with cytoplasmic giantin-based intermediate filaments, and such cells showed antiviral activity toward VSV.

Stephanie E. Hood
Dec 1, 2020; 61:1720-1732
Research Articles

Lipins are eukaryotic proteins with functions in lipid synthesis and the homeostatic control of energy balance. They execute these functions by acting as phosphatidate phosphatase enzymes in the cytoplasm and by changing gene expression after translocation into the cell nucleus, in particular under fasting conditions. Here, we asked whether nuclear translocation and the enzymatic activity of Drosophila Lipin serve essential functions and how gene expression changes, under both fed and fasting conditions, when nuclear translocation is impaired. To address these questions, we created a Lipin null mutant, a mutant expressing Lipin lacking a nuclear localization signal (Lipin^NLS), and a mutant expressing enzymatically dead Lipin. Our data support the conclusion that the enzymatic but not nuclear gene regulatory activity of Lipin is essential for survival. Notably, adult Lipin^NLS flies were not only viable but also exhibited improved life expectancy. In contrast, they were highly susceptible to starvation. Both the improved life expectancy in the fed state and the decreased survival in the fasting state correlated with changes in metabolic gene expression. Moreover, increased life expectancy of fed flies was associated with a decreased metabolic rate. Interestingly, in addition to metabolic genes, genes involved in feeding behavior and the immune response were misregulated in Lipin^NLS flies. Altogether, our data suggest that the nuclear activity of Lipin influences the genomic response to nutrient availability with effects on life expectancy and starvation resistance. Thus, nutritional or therapeutic approaches that aim at lowering nuclear translocation of lipins in humans may be worth exploring.

α-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson's disease (PD). It is an intrinsically disordered protein that binds acidic phospholipids. Growing evidence supports a role for α-Syn in membrane trafficking, including, mechanisms of endocytosis and exocytosis, although the exact role of α-Syn in these mechanisms is currently unclear. Here we investigate the associations of α-Syn with the acidic phosphoinositides (PIPs), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2). Our results show that α-Syn colocalizes with PIP2 and the phosphorylated active form of the clathrin adaptor protein 2 (AP2) at clathrin-coated pits. Using endocytosis of transferrin as an indicator for clathrin-mediated endocytosis (CME), we find that α-Syn involvement in endocytosis is specifically mediated through PI(4,5)P2 levels on the plasma membrane. In accord with their effects on PI(4,5)P2 levels, the PD associated A30P, E46K, and A53T mutations in α-Syn further enhance CME in neuronal and nonneuronal cells. However, lysine to glutamic acid substitutions at the KTKEGV repeat domain of α-Syn, which interfere with phospholipid binding, are ineffective in enhancing CME. We further show that the rate of synaptic vesicle (SV) endocytosis is differentially affected by the α-Syn mutations and associates with their effects on PI(4,5)P2 levels, however, with the exception of the A30P mutation. This study provides evidence for a critical involvement of PIPs in α-Syn–mediated membrane trafficking.

AAA+ ATPases constitute a large family of proteins that are involved in a plethora of cellular processes including DNA disassembly, protein degradation and protein complex disassembly. They typically form a hexametric ring-shaped structure with six subunits in a (pseudo) 6-fold symmetry. In a subset of AAA+ ATPases that facilitate protein unfolding and degradation, six subunits cooperate to translocate protein substrates through a central pore in the ring. The number and type of nucleotides in an AAA+ ATPase hexamer is inherently linked to the mechanism that underlies cooperation among subunits and couples ATP hydrolysis with substrate translocation. We conducted a native MS study of a monodispersed form of PAN, an archaeal proteasome AAA+ ATPase, to determine the number of nucleotides bound to each hexamer of the WT protein. We utilized ADP and its analogs (TNP-ADP and mant-ADP), and a nonhydrolyzable ATP analog (AMP-PNP) to study nucleotide site occupancy within the PAN hexamer in ADP- and ATP-binding states, respectively. Throughout all experiments we used a Walker A mutant (PAN^K217A) that is impaired in nucleotide binding as an internal standard to mitigate the effects of residual solvation on mass measurement accuracy and to serve as a reference protein to control for nonspecific nucleotide binding. This approach led to the unambiguous finding that a WT PAN hexamer carried – from expression host – six tightly bound ADP molecules that could be exchanged for ADP and ATP analogs. Although the Walker A mutant did not bind ADP analogs, it did bind AMP-PNP, albeit at multiple stoichiometries. We observed variable levels of hexamer dissociation and an appearance of multimeric species with the over-charged molecular ion distributions across repeated experiments. We posit that these phenomena originated during ESI process at the final stages of ESI droplet evolution.

Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.

Nuclear Disarmament and the Protection of Cultural Heritage Research paper sysadmin 6 October 2017

States possessing nuclear weapons should be called upon to consider and publish the risks posed to cultural heritage, and their mitigation strategies, in their nuclear-weapons doctrines and policies.

Summary

• Renewed risk assessments for nuclear weapons and policies are taking place around the world in light of nuclear modernization and the changing geostrategic environment that is making the use of nuclear weapons more likely. As such the humanitarian impacts of nuclear weapons and tests have received increased attention. However, the effect on cultural heritage has so far been neglected.
• The potential for armed conflict to destroy cultural heritage has been recognized in international law since 1954. There is significant evidence on the impact of nuclear weapons on cultural heritage including the consequences of their use in Hiroshima and Nagasaki and the effect of nuclear-testing programmes in places of cultural significance since 1945. States that possess nuclear weapons have increased liabilities and responsibilities to protect cultural heritage and cultural rights. The need to protect cultural heritage should strengthen the case for reducing and eliminating nuclear weapons.
• Failure to take into account the protection of heritage in the development of nuclear weapons policies – including disarmament, non-proliferation and arms-control negotiations – significantly undermines states’ existing commitments to protecting heritage threatened by conflict.
• Risk assessments of the impact of nuclear weapons on cultural heritage and important cultural artefacts – and methods of preventing such catastrophic damage – should be part of protecting cultural heritage in every country and the subject of informed public debate. A new body of knowledge on the full range of nuclear weapons impacts would introduce a fresh perspective to inform decision-makers, international organizations and the public in thinking about nuclear weapons policies and practices.
• Risk and resilience frameworks, which provide sets of solutions for risk assessments, would allow assessments of nuclear weapons threats to heritage and highlight vulnerabilities that need to be addressed. Such frameworks would provide a basis for policymakers to identify the world’s cultural heritage most at risk and help develop mitigation strategies to ensure that it is protected. In particular, states possessing nuclear weapons should be called upon to consider and publish the risks posed to cultural heritage, and their mitigation strategies, in their nuclear weapons doctrines and policies, as a contribution to transparency and confidence-building, and as a responsibility to the world’s shared heritage. International organizations, such as the UN Educational, Scientific, and Cultural Organization (UNESCO), have a role to play in bridging security perspectives with protecting cultural heritage.

In nucleotide excision repair, bulky DNA lesions such as UV-induced cyclobutane pyrimidine dimers are removed from the genome by concerted dual incisions bracketing the lesion, followed by gap filling and ligation. So far, two dual-incision patterns have been discovered: the prokaryotic type, which removes the damage in 11–13-nucleotide-long oligomers, and the eukaryotic type, which removes the damage in 24–32-nucleotide-long oligomers. However, a recent study reported that the UvrC protein of Mycobacterium tuberculosis removes damage in a manner analogous to yeast and humans in a 25-mer oligonucleotide arising from incisions at 15 nt from the 3´ end and 9 nt from the 5´ end flanking the damage. To test this model, we used the in vivo excision assay and the excision repair sequencing genome-wide repair mapping method developed in our laboratory to determine the repair pattern and genome-wide repair map of Mycobacterium smegmatis. We find that M. smegmatis, which possesses homologs of the Escherichia coli uvrA, uvrB, and uvrC genes, removes cyclobutane pyrimidine dimers from the genome in a manner identical to the prokaryotic pattern by incising 7 nt 5´ and 3 or 4 nt 3´ to the photoproduct, and performs transcription-coupled repair in a manner similar to E. coli.

In eukaryotic DNA replication, DNA polymerase ε (Polε) is responsible for leading strand synthesis, whereas DNA polymerases α and δ synthesize the lagging strand. The human Polε (hPolε) holoenzyme is comprised of the catalytic p261 subunit and the noncatalytic p59, p17, and p12 small subunits. So far, the contribution of the noncatalytic subunits to hPolε function is not well understood. Using pre-steady-state kinetic methods, we established a minimal kinetic mechanism for DNA polymerization and editing catalyzed by the hPolε holoenzyme. Compared with the 140-kDa N-terminal catalytic fragment of p261 (p261N), which we kinetically characterized in our earlier studies, the presence of the p261 C-terminal domain (p261C) and the three small subunits increased the DNA binding affinity and the base substitution fidelity. Although the small subunits enhanced correct nucleotide incorporation efficiency, there was a wide range of rate constants when incorporating a correct nucleotide over a single-base mismatch. Surprisingly, the 3'→5' exonuclease activity of the hPolε holoenzyme was significantly slower than that of p261N when editing both matched and mismatched DNA substrates. This suggests that the presence of p261C and the three small subunits regulates the 3'→5' exonuclease activity of the hPolε holoenzyme. Together, the 3'→5' exonuclease activity and the variable mismatch extension activity modulate the overall fidelity of the hPolε holoenzyme by up to 3 orders of magnitude. Thus, the presence of p261C and the three noncatalytic subunits optimizes the dual enzymatic activities of the catalytic p261 subunit and makes the hPolε holoenzyme an efficient and faithful replicative DNA polymerase.

A new nuclear order 7 February 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 26 January 2023 Chatham House and Online

In conversation with Rafael Mariano Grossi.

For more than half a century, the global nuclear non-proliferation framework has supported international security and facilitated the expansion of the many peaceful applications of nuclear science and technology. 

What is happening today in Ukraine, Iran and North Korea, not only challenges the way we deal with the existential threat of nuclear weapons, but also the impact it could have on addressing another existential threat – climate change.

Russia’s invasion of Ukraine is the biggest test to global resolve both in avoiding nuclear conflict and in ensuring the safety of one of the biggest nuclear power programmes in Europe.

Rafael Mariano Grossi of the International Atomic Energy Agency discusses key questions on global nuclear cooperation including:

• The impact of the war in Ukraine and issues with Iran and North Korea on countries’ risk assessment with regards to nuclear non-proliferation.

• What the IAEA’s on-the-ground presence and the director general’s missions to Ukraine, particularly the Zaporizhzhia Nuclear Power Plant, tells us about what is necessary – now and in the long term – to ensure the safety and security of nuclear material under all circumstances.

• The role of ensuring nuclear energy can play its vital part in mitigating climate change now and in the future.

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

Read the transcript.

Preclinical data have shown that ¹⁶¹Tb-labeled peptides targeting the somatostatin receptor are therapeutically more effective for peptide receptor radionuclide therapy than are their ¹⁷⁷Lu-labeled counterparts. To further substantiate this enhanced therapeutic effect, we performed cellular dosimetry to quantify the absorbed dose to the cell nucleus and compared dose–response curves to evaluate differences in relative biological effectiveness in vitro. Methods: CA20948 cell survival was assessed after treatment with [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTATATE (agonist) and with [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTA-LM3 (antagonist) via a clonogenic assay. Cell binding, internalization, and dissociation assays were performed up to 7 d to acquire time-integrated activity coefficients. Separate S values for each type of particle emission (Auger/internal conversion [IC] electrons and β^– particles) were computed via Monte Carlo simulations, while considering spheric cells. Once the absorbed dose to the cell nucleus was calculated, survival curves were fitted to the appropriate linear or linear-quadratic model and corresponding relative biological effectiveness was evaluated. Results: Although the radiopeptide uptake was independent of the radionuclide, [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 delivered a 3.6 and 3.8 times higher dose to the nucleus, respectively, than their ¹⁷⁷Lu-labeled counterparts on saturated receptor binding. This increased nucleus-absorbed dose was mainly due to the additional emission of IC and not Auger electrons by ¹⁶¹Tb. When activity concentrations were considered, both [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 showed a lower survival fraction than did labeling with ¹⁷⁷Lu. When the absorbed dose to the nucleus was considered, no significant difference could be observed between the dose–response curves for [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTATATE. [¹⁶¹Tb]Tb-DOTA-LM3 showed a linear-quadratic dose response, whereas [¹⁶¹Tb]Tb-DOTATATE showed only a linear dose response within the observed dose range, suggesting additional cell membrane damage by Auger electrons. Conclusion: The IC, rather than Auger, electrons emitted by ¹⁶¹Tb resulted in a higher absorbed dose to the cell nucleus and lower clonogenic survival for [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 than for the ¹⁷⁷Lu-labeled analogs. In contrast, [¹⁶¹Tb]Tb-DOTATATE showed no higher dose response than [¹⁷⁷Lu]Lu-DOTATATE, whereas for [¹⁶¹Tb]Tb-DOTA-LM3 an additional quadratic response was observed. Because of this quadratic response, potentially caused by cell membrane damage, [¹⁶¹Tb]Tb-DOTA-LM3 is a more effective radiopeptide than [¹⁶¹Tb]Tb-DOTATATE for labeling with ¹⁶¹Tb.

Bispecific antibodies (bsAbs) are engineered to target 2 different epitopes simultaneously. About 75% of the 16 clinically approved bsAbs have entered the clinic internationally since 2022. Hence, research on biomedical imaging of various radiolabeled bsAb scaffolds may serve to improve patient selection for bsAb therapy. Here, we provide a comprehensive overview of recent advances in radiolabeled bsAbs for imaging via PET or SPECT. We compare direct targeting and pretargeting approaches in preclinical and clinical studies in oncologic research. Furthermore, we show preclinical applications of imaging bsAbs in neurodegenerative diseases. Finally, we offer perspectives on the future directions of imaging bsAbs based on their challenges and opportunities.

Earlier this month, the United States and the Republic of Korea reached an agreement on greater cooperation on civil nuclear energy projects, the U.S. Department of Energy said this week.

NEW YORK, Nov. 1, 2024 — NANO Nuclear Energy Inc. has announced the October 29, 2024 closing of the sale of an additional 317,646 shares of its common stock at […]

The post NANO Nuclear Energy Raises Over $40M from Recent Underwritten Follow-On Offering appeared first on HPCwire.

The Vancouver Canucks take on the Calgary Flames on Tuesday night.

Jonathan Lekkerimäki will make his NHL debut when the Vancouver Canucks take on the Calgary Flames on Tuesday night.

The Calgary Flames' fifth game in eight nights and three time zones was a tough one they need to learn from

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

Neuronal cytotoxic edema is implicated in neuronal injury and death, yet mitigating brain edema with osmotic and surgical interventions yields poor clinical outcomes. Importantly, neuronal swelling and its downstream consequences during early brain development remain poorly investigated, and new treatment approaches are needed. We explored Ca²⁺-dependent downstream effects after neuronal cytotoxic edema caused by diverse injuries in mice of both sexes using multiphoton Ca²⁺ imaging in vivo [Postnatal Day (P)12–17] and in acute brain slices (P8–12). After different excitotoxic insults, cytosolic GCaMP6s translocated into the nucleus after a few minutes in a subpopulation of neurons, persisting for hours. We used an automated morphology-detection algorithm to detect neuronal soma and quantified the nuclear translocation of GCaMP6s as the nuclear to cytosolic intensity (N/C ratio). Elevated neuronal N/C ratios occurred concurrently with persistent elevation in Ca²⁺ loads and could also occur independently from neuronal swelling. Electron microscopy revealed that the nuclear translocation was associated with the increased nuclear pore size. The nuclear accumulation of GCaMP6s in neurons led to neocortical circuit dysfunction, mitochondrial pathology, and increased cell death. Inhibiting calpains, a family of Ca²⁺-activated proteases, prevented elevated N/C ratios and neuronal swelling. In summary, in the developing brain, we identified a calpain-dependent alteration of nuclear transport in a subpopulation of neurons after disease-relevant insults leading to long-term circuit dysfunction and cell death. The nuclear translocation of GCaMP6 and other cytosolic proteins after acute excitotoxicity can be an early biomarker of brain injury in the developing brain.

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.

The superior colliculus receives a direct projection from retinal ganglion cells. In primates, it remains unknown if the same ganglion cells also supply the lateral geniculate nucleus. To address this issue, a double-label experiment was performed in two male macaques. The animals fixated a target while injection sites were scouted in the superior colliculus by recording and stimulating with a tetrode. Once suitable sites were identified, cholera toxin subunit B-Alexa Fluor 488 was injected via an adjacent micropipette. In a subsequent acute experiment, cholera toxin subunit B-Alexa Fluor 555 was injected into the lateral geniculate nucleus at matching retinotopic locations. After a brief survival period, ganglion cells were examined in retinal flatmounts. The percentage of double-labeled cells varied locally, depending on the relative efficiency of retrograde transport by each tracer and the precision of retinotopic overlap of injection sites in each target nucleus. In counting boxes with extensive overlap, 76–98% of ganglion cells projecting to the superior colliculus were double labeled. Cells projecting to the superior colliculus constituted 4.0–6.7% of the labeled ganglion cell population. In one particularly large zone, there were 5,746 cells labeled only by CTB-AF555, 561cells double labeled by CTB-AF555 and CTB-AF488, but no cell labeled only by CTB-AF488. These data indicate that retinal input to the macaque superior colliculus arises from a collateral axonal branch supplied by ~5% of the ganglion cells that project to the lateral geniculate nucleus. Surprisingly, there exist no ganglion cells that project exclusively to the SC.

The technology, enabled by thorium atoms, could keep time more accurately than atomic clocks and enable new discoveries about gravity, gravitational waves and dark matter

The grassroots organization, Nihon Hidankyo, was lauded for "demonstrating through witness testimony that nuclear weapons must never be used again"

Stefano Terlizzi joined the Ken and Mary Alice Lindquist Department of Nuclear Engineering as the John and Jean M. Brennan Clean Energy Early Career Professor on July 22. In this Q&A, Terlizzi talks about his research background and interests, why he chose Penn State and more.

This week SA Money Report tries to understand eThekwini's surprising plan for nuclear power, and whether the ANC's RET faction has a hand in things.

India has ambitious plans to set up nuclear reactors across the country, especially in states where thermal power plants have either completed its life, or where access to coal is a challenge.

India has ambitious plans to set up nuclear reactors across the country, especially in states where thermal power plants have either completed its life, or where access to coal is a challenge.

NASA’s Power to Explore Challenge calls on U.S. students to submit ideas for moon missions powered by radioisotope systems. The contest encourages kindergarten through Year 12 students to envision a mission, detail objectives, and apply their unique “power” to achieve mission success. Entries are due by January 31, 2025, and grand prize winners will tour NASA’s Glenn Research Center, gaining insight into the technology and science of space exploration.

Read the in depth Review of Intel NUC 11 Extreme PC Components. Know detailed info about Intel NUC 11 Extreme configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

[Namibian] Russian company Rosatom and South African AllWeld Nuclear and Industrial are joining forces to promote the sustainable development of nuclear energy in Africa.

BAKU, Azerbaijan — The head of the United Nations' nuclear watchdog said Tuesday he's hopeful that meetings this week with Iranian officials, including the country's new president, can lead to a breakthrough in monitoring the country's nuclear program, a longstanding issue that has gained new urgency as Israel has twice struck Iran amid rising tensions in the Middle East. Rafael Mariano Grossi, director general of the International Atomic Energy Agency, will travel to Iran on Wednesday to meet for the first time with President Masoud Pezeshkian, who was elected in July. Grossi said he hopes to build on positive discussions he had with Iranian Foreign Minister Abbas Araghchi during the U.N. General Assembly in September. "We have a problem that we need to solve," Grossi said in an interview at the U.N. climate conference in Azerbaijan. "That is this gap, this lack of confidence, which we should not allow to grow into a self-fulfilling prophecy of using nuclear facilities as targets." He added: "There has been a bit of a dire straits dynamic with Iran that we want to go beyond." Iran is rapidly advancing its atomic program while increasing stockpiles of uranium enriched to near weapons-grade levels, all in defiance of international demands, according to the IAEA. Iran says its program is for energy purposes, not to build weapons. Grossi's visit comes as Israel and Iran have traded missile attacks in recent months after more than a year of war in Gaza, which is governed by Hamas, a group supported by Iran. Grossi noted that international law prohibits the attack of nuclear facilities and "it's obvious that is something that can have radiological consequences." The Biden administration said last month that it had won assurances from Israel that it would not attack nuclear or oil sites. A 2015 nuclear agreement between Iran and world powers put limits on Iran's nuclear program, which the West fears could be used to make nuclear weapons. The deal included the lifting of economic sanctions on Iran. But that deal collapsed after Donald Trump's administration in 2018 pulled the United States from it. That led Iran to abandon all limits put on its program and enrich uranium to up to 60% purity. When asked if the IAEA feared Iran may be developing a bomb, Grossi said he didn't "have any information that would sustain that." He added that inspectors' job was not to "judge intentions," but rather verify that what Iran says about its nuclear program was true. Trump's reelection last week raises questions about whether and how the incoming administration and Iran may engage. Grossi said he had worked with the first Trump administration, which he said engaged in "seamless, professional work," and looked forward to looking with Trump's second administration. "Circumstances have changed in that the problem has grown bigger than it was," said Grossi. "The problem of not finding a solution."

Solar power is now priced competitively with traditional forms of energy, which makes new nuclear power plants financially unviable.

North Korea conducted its fourth hydrogen bomb test last week, and reactions from around the world have ranged from outrage and alarm to dismissiveness.

The warnings from the United Nations and from anti-nuclear activists are increasingly ominous: the world is closer to a nuclear war—by design or by accident—more than ever before. The current conflicts—and the intense war of words—between nuclear and non-nuclear states—Russia vs. Ukraine, Israel vs. Palestine and North Korea vs. South Korea—are adding fuel to a […]

In recent years, the rhetoric, strategy and practice of nuclear deterrence has grown riskier, more urgent, more dangerous, less stable, and increasingly in the hands of deficient leaders and policymakers. Playing Nuclear Games The ten States that have manufactured and test detonated nuclear weapons since 1945, each have received and/or provided assistance to other States […]

The United Nations Secretary General António Guterres congratulated grassroots Japanese organization Nihon Hidankyo on being awarded the 2024 Nobel Peace Prize. “The atomic bomb survivors from Hiroshima and Nagasaki, also known as the hibakusha, are selfless, soul-bearing witnesses of the horrific human cost of nuclear weapons,” he said in a statement. “While their numbers grow smaller each […]

Satellite images show China working on nuclear reactor for new warship

India’s federal power minister on Tuesday asked the states that are away from coal resources to consider setting up nuclear-based power plants, besides identifying and listing the power utilities to meet investments to support growing power demand.

The Indian government in its federal budget this year had proposed to partner with private players to develop small nuclear reactors to increase the amount of electricity from sources that do not produce carbon dioxide emissions.

States should consider setting up nuclear power plants at the sites where coal-based thermal power plants have completed their life, Manohar Lal, the country’s power minister, told states as per a government statement.

India’s stringent nuclear compensation laws have hampered talks with foreign power plant builders such as General Electric GE.N and Westinghouse.

The country, which currently has about 8 gigawatts of nuclear capacity, aims to increase it to 20 GW by 2032.

The minister also asked the states to identify and list their power utilities in the country’s stock exchange to meet increasing investment demand in the power sector as well as improve the transmission system to add more renewable capacity.

India has pledged to achieve a net zero carbon emission target by 2070 and has a target of 500 GW of renewable energy by 2030.

Two important barriers to a stable, powerful fusion reaction have been leapt by an experiment in a small tokamak reactor, but we don’t yet know if the technique will work in larger devices

Concern over the risks of enabling nuclear weapons development is usually focused on nuclear fission reactors, but the potential harm from more advanced fusion reactors has been underappreciated

Two types of fusion reactor called tokamaks and stellarators both have drawbacks – but a new design combining parts from both could offer the best of both worlds

Smashing gold nuclei together at high speeds billions of times has resulted in 16 particles of antihyperhydrogen-4, a very exotic and heavy form of antimatter

These stunning photographs are all shortlisted for the Sony World Photography Awards 2024

Pregnane X receptor (PXR) belongs to the nuclear receptor superfamily that plays a crucial role in hepatic physiologic and pathologic conditions. Phase separation is a process in which biomacromolecules aggregate and condense into a dense phase as liquid condensates and coexist with a dilute phase, contributing to various cellular and biologic functions. Until now, whether PXR could undergo phase separation remains unclear. This study aimed to investigate whether PXR undergoes phase separation. Analysis of the intrinsically disordered regions (IDRs) using algorithm tools indicated a low propensity of PXR to undergo phase separation. Experimental assays such as hyperosmotic stress, agonist treatment, and optoDroplets assay demonstrated the absence of phase separation for PXR. OptoDroplets assay revealed the inability of the fusion protein of Cry2 with PXR to form condensates upon blue light stimulation. Moreover, phase separation of PXR did not occur even though the mRNA and protein expression levels of PXR target, cytochrome P450 3A4, changed after sorbitol treatment. In conclusion, for the first time, these findings suggested that exogenous PXR does not undergo phase separation following activation or under hyperosmotic stress in nucleus of cells.

The diagnostic work-up of patients with fever of unknown origin (FUO) begins with a thorough history and physical examination, complete blood count with differential, chest x-ray, urinalysis and culture, electrolyte panel, liver enzymes, erythrocyte sedimentation rate, and C-reactive protein level. Additional imaging procedures, including nuclear medicine tests, are generally used as second-line procedures, with ¹⁸F-FDG PET and PET/CT assuming increasingly important roles in the diagnostic work-up. The Society of Nuclear Medicine and Molecular Imaging, the Infectious Diseases Society of America, and the American College of Nuclear Medicine convened an autonomous expert work group to comprehensively review the published literature for nuclear imaging in adults and children with FUO and establish appropriate use criteria (AUC). This process was performed in accordance with the Protecting Access to Medicare Act of 2014, which requires that all referring physicians consult AUC by using a clinical decision support mechanism before ordering advanced diagnostic imaging services. The complete findings and discussions of the work group were published on January 8, 2023, and are available at https://www.snmmi.org/ClinicalPractice/content.aspx?ItemNumber=15666. The AUC in the final document are intended to assist referring health care providers in appropriate use of nuclear medicine imaging procedures in patients with FUO. The work group noted limitations in the current literature on nuclear medicine imaging for FUO, with the need for well-designed prospective multicenter investigations. Consensus findings from published data and expert opinions were used to create recommendations in common clinical scenarios for adults and children. Included in the complete document is a discussion of inflammation of unknown origin (IUO), a recently described entity. In view of the fact that the criteria for FUO and IUO are similar (except for fever > 38.3°C [100.9°F]) and that the most common etiologies of these 2 entities are similar, it is the expert opinion of the work group that the recommendations for nuclear medicine imaging of FUO are also applicable to IUO. These recommendations are included in the full guidance document. This summary reviews rationale, methodology, and main findings and refers the reader to the complete AUC document.

The role of gastrin-releasing peptide receptor (GRPR) in various diseases, including cancer, has been extensively studied and has emerged as a promising therapeutic target. In this study, we successfully achieved the use of [²¹²Pb]Pb-DOTAM-GRPR1, comprising the α-particle generator, ²¹²Pb, combined with a GRPR-targeting peptide, GRPR1, in a prostate cancer model. Methods: Pharmacokinetics, toxicity, radiation dosimetry, and efficacy were assessed in GRPR-positive prostate tumor–bearing mice after intravenous administration of [²¹²Pb]Pb-DOTAM-GRPR1 (where DOTAM is 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane). Results: Preclinical studies have shown tumor targeting of up to 5 percent injected dose per gram over 24 h, and optimization of the drug formulation and quantity has led to minimized oxidation and off-target binding, respectively. Particularly, an increase in peptide amount from 28 to 280 ng was shown to reduce off-target uptake, especially at the level of the pancreas, by about 30%. Furthermore, dosimetry studies confirmed the kidney as the dose-limiting organ, and toxicity studies revealed that a nontoxic dose of up to 1,665 kBq could be injected into mice. Efficacy studies indicated a median survival time of 9 wk in the control group, which received only a buffer solution, compared with 19 wk in the group that received 4 injections of 370 kBq at 3-wk intervals. Conclusion: Taken together, these combined data demonstrate the safety, tolerability, and efficacy of [²¹²Pb]Pb-DOTAM-GRPR1, thus warranting further exploration in clinical trials.