bluuebunny/crossref_metadata_2025 huggingface dataset:
LGR4 is essential for maintaining β-cell homeostasis through suppression of RANK
Authors: Filipowska Joanna , Cisneros Zelda , Leon-Rivera Nancy , Wang Peng , Kang Randy , Lu Geming , Yuan Yate-Ching , Bhattacharya Supriyo , Dhawan Sangeeta , Garcia-Ocaña Adolfo , Kondegowda Nagesha Guthalu , Vasavada Rupangi C.
Published: May 2024

Pancreatic β-cell stress contributes to diabetes progression. This study demonstrates that Leucine-rich repeat-containing G-protein-coupled-receptor-4 (LGR4) is critical for maintaining β-cell health and is modulated by stressors.In vitro,Lgr4knockdown decreases proliferation and survival in rodent β-cells, while overexpression protects against cytokine-induced cell death in rodent and human β-cells. Mechanistically, LGR4 suppresses Receptor Activator of Nuclear Factor Kappa B (NFκB) (RANK) and its subsequent activation of NFκB to protect β-cells. β-cell-specificLgr4-conditional knockout (cko) mice exhibit normal glucose homeostasis but increased β-cell death in both sexes and decreased proliferation only in females. MaleLgr4cko mice under stress display reduced β-cell proliferation and a further increase in β-cell death. Upon aging, both male and femaleLgr4cko mice display impaired β-cell homeostasis, however, only female mice are glucose intolerant with decreased plasma insulin. We show that LGR4 is required for maintaining β-cell health under basal and stress-induced conditions, through suppression of RANK.

Teaser

LGR4 receptor is critical for maintaining β-cell health under basal and stressed conditions, through suppression of RANK.
Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses
Authors: Turpin Rita , Peltonen Karita , Rannikko Jenna H. , Liu Ruixian , Kumari Anita N. , Nicorici Daniel , Lee Moon Hee , Mutka Minna , Kovanen Panu E. , Niinikoski Laura , Meretoja Tuomo , Mattson Johanna , Järvinen Petrus , Lahdensuo Kanerva , Järvinen Riikka , Tornberg Sara , Mirtti Tuomas , Boström Pia , Koskivuo Ilkka , Thotakura Anil , Pouwels Jeroen , Hollmén Maija , Mustjoki Satu , Klefström Juha
Published: May 2024

Tumor-resident immune cells play a crucial role in eliciting anti-tumor immunity and immunomodulatory drug responses, yet these functions have been difficult to study without tractable models of tumor immune microenvironment (TIME). Patient-derivedex vivomodels contain authentic resident immune cells and therefore, could provide new mechanistic insights into how TIME responds to tumor or immune cell-directed therapies. Here, we assessed the reproducibility and robustness of immunomodulatory drug responses across two differentex vivomodels of breast cancer TIME and one of renal cell carcinoma. These independently developed TIME models were treated with a panel of clinically relevant immunomodulators, revealing remarkably similar changes in gene expression and cytokine profiles among the three models in response to T cell activation and STING-agonism while still preserving individual patient-specific response patterns. Moreover, we found two common core signatures of adaptive or innate immune responses present across all three models and both types of cancer, potentially serving as a benchmark for drug-induced immune activation inex vivomodels of TIME. The robust reproducibility of immunomodulatory drug responses observed across diverseex vivomodels of TIME underscores the significance of human patient-derived models in elucidating the complexities of antitumor immunity and therapeutic interventions.
Caspase-11 drives macrophage hyperinflammation in models of Polg-related mitochondrial disease
Authors: VanPortfliet Jordyn J. , Lei Yuanjiu , Ramanathan Muthumeena , Martinez Camila Guerra , Wong Jessica , Stodola Tim J. , Hoffmann Brian R. , Pflug Kathryn , Sitcheran Raquel , Kneeland Stephen C. , Murray Stephen A. , McGuire Peter. J. , Cannon Carolyn L. , West A. Phillip
Published: May 2024

Mitochondrial diseases (MtD) represent a significant public health challenge due to their heterogenous clinical presentation, often severe and progressive symptoms, and lack of effective therapies. Environmental exposures, such bacterial and viral infection, can further compromise mitochondrial function and exacerbate the progression of MtD. Infections in MtD patients more frequently progress to sepsis, pneumonia, and other detrimental inflammatory endpoints. However, the underlying immune alterations that enhance immunopathology in MtD remain unclear, constituting a key gap in knowledge that complicates treatment and increases mortality in this vulnerable population. Here we employ in vitro and in vivo approaches to clarify the molecular and cellular basis for innate immune hyperactivity in models of polymerase gamma (Polg)-related MtD. We reveal that type I interferon (IFN-I)-mediated upregulation of caspase-11 and guanylate-binding proteins (GBPs) increase macrophage sensing of the opportunistic microbePseudomonas aeruginosa(PA) inPolgmutant mice. Furthermore, we show that excessive cytokine secretion and activation of pyroptotic cell death pathways contribute to lung inflammation and morbidity after infection with PA. Our work sheds new light on innate immune dysregulation in MtD and reveals potential targets for limiting infection- and inflammation-related complications in Polg-related MtD.
Targeting PI3K-gamma in myeloid driven tumour immune suppression: A Systematic Review and Meta-Analysis of the Preclinical Literature
Authors: Xu H , Russell SN , Steiner K , O’Neill E , Jones KI
Published: May 2024

The intricate interplay between immune and stromal cells within the tumour microenvironment (TME) significantly influences tumour progression. Myeloid cells, including tumour-associated macrophages (TAMs), neutrophils (TANs), and myeloid-derived suppressor cells (MDSCs), contribute to immune suppression in the TME1,2. This poses a significant challenge for novel immunotherapeutics that rely on host immunity to exert their effect. This systematic review explores the preclinical evidence surrounding the inhibition of phosphoinositide 3-kinase gamma (PI3Kγ) as a strategy to reverse myeloid-driven immune suppression in solid tumours.

EMBASE, MEDLINE, and PubMed databases were searched on 6thOctober 2022 using keyword and subject heading terms to capture relevant studies. The studies, focusing on PI3Kγ inhibition in animal models, were subjected to predefined inclusion and exclusion criteria. Extracted data included tumour growth kinetics, survival endpoints, and immunological responses which were meta-analysed. PRISMA and MOOSE guidelines were followed.

A total of 36 studies covering 73 animal models were included in the review and meta-analysis. Tumour models covered breast, colorectal, lung, skin, pancreas, brain, liver, prostate, head and neck, soft tissue, gastric, and oral cancer. The predominant PI3Kγ inhibitors were IPI-549 and TG100-115, demonstrating favourable specificity for the gamma isoform. Combination therapies, often involving chemotherapy, radiotherapy, immune checkpoint inhibitors, biological agents, or vaccines, were explored in 81% of studies. Analysis of tumour growth kinetics revealed a statistically significant though heterogeneous response to PI3Kγ monotherapy, whereas the tumour growth in combination treated groups were more consistently reduced. Survival analysis showed a pronounced increase in median overall survival with combination therapy.

This systematic review provides a comprehensive analysis of preclinical studies investigating PI3Kγ inhibition in myeloid-driven tumour immune suppression. The identified studies underscore the potential of PI3Kγ inhibition in reshaping the TME by modulating myeloid cell functions. The combination of PI3Kγ inhibition with other therapeutic modalities demonstrated enhanced antitumor effects, suggesting a synergistic approach to overcome immune suppression. These findings support the potential of PI3Kγ-targeted therapies, particularly in combination regimens, as a promising avenue for future clinical exploration in diverse solid tumour types.

Graphical abstract
Population origin, body mass, and viral infections influence drone honey bee (Apis mellifera) heat tolerance
Authors: McAfee Alison , Metz Bradley N , Connor Patrick , Du Keana , Allen Christopher W , Frausto Luis A , Swenson Mark P , Phillips Kylah S , Julien Madison , Baer Boris , Tarpy David R , Foster Leonard J
Published: May 2024

Extreme temperatures associated with climate change are expected to impact the physiology and fertility of a variety of insects, including honey bees. Most previous work has focused on female honey bees, and comparatively little research has investigated how heat exposure affects males (drones). To address this gap, we tested how body mass, viral infections, Africanization, and geographic origin (including stocks from Australia, California, and Ukraine as well as diverse locations within British Columbia, Canada) influenced drone and sperm heat tolerance. We found that individual body size was highly influential, with heavier drones being more likely to survive a heat challenge than smaller drones. Drones originating from feral colonies in Southern California (which are enriched for African genetics) were also more likely to survive a heat challenge than drones originating from commercially-supplied Californian stock. We found no association between drone mass and thermal tolerance of sperm over time in anin vitrochallenge assay, but experimental viral infection decreased the heat tolerance of sperm. Overall, there is ample variation in sperm heat tolerance, with sperm from some groups displaying remarkable heat resilience and sperm from others being highly sensitive, with additional factors influencing heat tolerance of the drones themselves.
Predicting local control of brain metastases after stereotactic radiotherapy with clinical, radiomics and deep learning features
Authors: Kanakarajan Hemalatha , Baene Wouter De , Hanssens Patrick , Sitskoorn Margriet
Published: May 2024

Background and purpose

Timely identification of local failure after stereotactic radiotherapy for brain metastases allows for treatment modifications, potentially improving outcomes. Previous studies showed that adding radiomics or Deep Learning (DL) features to clinical features increased Local Control (LC) prediction accuracy. However, no study has integrated radiomics, DL, and clinical features into machine learning algorithms to predict LC. We examined whether a model using all these features achieves better accuracy than models using only a subset.

Materials and methods

We collected pre-treatment brain MRIs and clinical data for 129 patients at the Gamma Knife Center of the Elisabeth-TweeSteden Hospital. Radiomics features (extracted using the Python radiomics feature extractor) and DL features (extracted using a 3D ResNet model) were combined with clinical features. Performance of a Random Forest classifier was compared across four models trained with: clinical features only; clinical and radiomics features; clinical and DL features; and clinical, radiomics, and DL features.

Results

The prediction model utilizing only clinical variables provided an Area Under the receiver operating characteristic Curve (AUC) of 0.82 and an accuracy of 75.6%. Adding radiomics features increased the AUC to 0.88 and accuracy to 83.3%, while adding DL features resulted in an AUC of 0.86 and accuracy of 78.3%. The best performance came from combining clinical, radiomics, and DL features, achieving an AUC of 0.89 and accuracy of 87%.

Conclusion

Integrating radiomics and DL features with clinical characteristics improves LC prediction after stereotactic radiotherapy for brain metastases. These findings demonstrate the potential for early outcome prediction, enabling timely treatment modifications to improve patient management.

Clinical and Translational Impact Statement

Our study holds great clinical value, as the increased prediction accuracy can lead to tailored and effective interventions, resulting in better outcomes for brain metastases patients treated with stereotactic radiotherapy.
BCL-2 and BOK regulate apoptosis by interaction of their C-terminal transmembrane domains
Authors: Beigl Tobias B. , Paul Alexander , Fellmeth Thomas , Nguyen Dang , Barber Lynn , Weller Sandra , Schäfer Benjamin , Gillissen Bernhard F. , Aulitzky Walter E. , Kopp Hans-Georg , Rehm Markus , Andrews David W. , Pluhackova Kristyna , Essmann Frank
Published: May 2024

The Bcl-2 family controls apoptosis by direct interactions of pro- and anti-apoptotic proteins. The principle mechanism is binding of the BH3 domain of pro-apoptotic proteins to the hydrophobic groove of anti-apoptotic siblings, which is therapeutically exploited by approved BH3-mimetic anti-cancer drugs. Evidence suggests that also the transmembrane domain (TMD) of Bcl-2 proteins affects Bcl-2 interactions. We developed a highly-specific split luciferase assay, enabling the analysis of TMD interactions of pore-forming apoptosis effectors BAX, BAK, and BOK with anti-apoptotic Bcl-2 proteins in living cells. We confirm homotypic interaction of the BAX-TMD, but also newly identify interaction of the TMD of anti-apoptotic BCL-2 with the TMD of BOK, a so far very peculiar pro-apoptotic Bcl-2 protein. Interaction of BOK-TMD with BCL-2-TMD localizes at the endoplasmic reticulum (ER). Molecular dynamics simulations in an ER membrane model confirm dynamic BOK-TMD and BCL-2-TMD homo- and heterodimers and stable heterotetramers. Inhibition of BOK-induced apoptosis by BCL-2 depends specifically on their TMDs. Thus, TMDs of Bcl-2 proteins are a relevant interaction interface for apoptosis regulation and provide a novel potential drug target.
Protein modelling and thermodynamics reveal that plant cation-chloride cotransporters mediate potassium-chloride symport
Authors: Henderson Sam W , Nourmohammadi Saeed , Hrmova Maria
Published: May 2024

Plant cation-chloride-cotransporters (CCC) are proposed to be Na+–K+–2Cl–transporting proteins, although phylogenetically they are closer to K+-Cl–cotransporters (KCC). Conserved features of plant CCC and animal KCC include the presence of predicted K+ and Cl– binding sites, and the absence of a Na+ binding site. Here, we investigated grapevine (Vitis vinifera L.) VvCCC using protein structural modelling and heterologous expression. Our modelling data predicted that 3D folds of VvCCC were more similar to DrNKCC1, but sequences of ion binding sites resembled those of hKCC1. The measurements with VvCCC-injected Xenopus laevis oocytes with VvCCC, localising to plasma membranes, indicated that oocytes were depleted of intracellular Cl–, net 86Rb fluxes, which agreed with thermodynamic predictions for KCC co-transport. 86Rb uptake by VvCCC-injected oocytes was Cl–-dependent, did not require external Na+, and was partially inhibited by the non-specific CCC blocker bumetanide – these properties are typical of KCC transporters. A loop diuretic-insensitive Na+ conductance in VvCCC-injected oocytes may account for earlier observations of Na+ uptake by plant CCC proteins in oocytes. Our data suggest plant CCC proteins are likely to function as K+-Cl– cotransporters, which opens avenues to define their mechanistic and biophysical properties and roles in physiology.
Combination of bortezomib and venetoclax targets the pro-survival function of LMP-1 and EBNA-3C of Epstein-Barr virus in post-transplant lymphoproliferative disorder
Authors: Tam Kam Pui , Xie Jia , Au-Yeung Rex Kwok Him , Chiang Alan Kwok Shing
Published: May 2024

Epstein-Barr virus (EBV) manipulates the ubiquitin-proteasome system and regulators of Bcl-2 family to enable the persistence of the virus and survival of the host cells through the expression of viral proteins in distinct latency patterns. We postulate that the combination of bortezomib (proteasome inhibitor) and venetoclax (Bcl-2 inhibitor) [bort/venetoclax] will cause synergistic killing of post-transplant lymphoproliferative disorder (PTLD) through targeting the pro-survival function of latent viral proteins such as latent membrane protein-1 (LMP-1) and EBV nuclear antigen-3C (EBNA-3C). Bort/venetoclax could synergistically kill spontaneous lymphoblastoid cell lines (sLCLs) derived from patients with PTLD and EBV-associated hemophagocytic lymphohistiocytosis by inducing DNA damage response, apoptosis and G1-S cell cycle arrest in a ROS-dependent manner. Bortezomib potently induced the expression of Noxa, a pro-apoptotic initiator and when combined with venetoclax, inhibited Mcl-1 and Bcl-2 simultaneously. Bortezomib prevented LMP-1 induced proteasomal degradation of IκBα leading to the suppression of the NF-κB signaling pathway. Bortezomib also rescued Bcl-6 from EBNA-3C mediated proteasomal degradation thus maintaining the repression of cyclin D1 and Bcl-2 causing G1-S arrest and apoptosis. Concurrently, venetoclax inhibited Bcl-2 upregulated by either LMP-1 or EBNA-3C. Bort/venetoclax decreased the expression of phosphorylated p65 and Bcl-2 at serine 70 thereby suppressing the NF-κB signaling pathway and promoting apoptosis, respectively. These data corroborated the marked suppression of the growth of xenograft of sLCL in SCID mice (p<0.001). Taken together, the combination of bortezomib and venetoclax targets the pro-survival function of LMP-1 and EBNA-3C of Epstein-Barr virus in post-transplant lymphoproliferative disorder.

Author Summary

Epstein-Barr virus (EBV) is an oncogenic virus associated with different cancers and can directly drive the development of a lymphoma type condition in organ transplant patients known as post-transplant lymphoproliferative disorder (PTLD) as a result of weakened immune surveillance of EBV. The malignant spectrum of PTLD will require multi-agent chemotherapy regimen which is not well tolerated by the immunocompromised patients. Here, we combined bortezomib (proteasome inhibitor) with venetoclax (Bcl-2 inhibitor) as a novel strategy to target the pro-survival function of key EBV onco-proteins, namely LMP-1 and EBNA-3C. We demonstrated that this chemotherapy-free regimen could be highly effective in killing patient-derived spontaneous lymphoblastoid cell lines which represent cell models of PTLD. The novel drug regimen can avoid the toxic effects of chemotherapy and may have high efficacy and specificity for the treatment of PTLD.
Multi-Omics Exploration of ABA Involvement in Identifying Unique Molecular Markers for Single and Combined Stresses in tomato plants
Authors: Pardo-Hernández Miriam , García-Pérez Pascual , Lucini Luigi , Rivero Rosa M
Published: May 2024

Over the past decade, our research group has found that plant responses to combined abiotic stresses are unique and cannot be inferred from studying plants exposed to individual stresses. Adaptive mechanisms involve changes in gene expression, ion regulation, hormonal balance, and metabolite biosynthesis or degradation. Understanding how these mechanisms integrate from stress perception to biochemical and physiological adjustments is a major challenge in abiotic stress signaling studies. Today, vast amounts of -omics data (genomics, transcriptomics, proteomics, metabolomics, phenomics) are readily available. Additonally, each –omic level is regulated and influenced by the others, highlighting the complexity of plant metabolism’s response to stress. Considering abscisic acid (ABA) as a key regulator in plant abiotic stress responses, in our study, ABA-deficient plants (flc) exposed to single or combined salinity and heat stresses were evaluated and different -omics analyses were conducted. Significant changes in biomass, photosynthesis, ions, transcripts, and metabolites occurred in mutant plants under single or combined stresses. Exogenous ABA application inflcmutants did not fully recover plant phenotypes or metabolic levels but induced cellular reprogramming with changes in specific markers. Multi-omics analysis aimed to identify ABA-dependent, ABA-independent, or stress-dependent markers in plant responses to single or combined stresses. We demonstrated that studying different -omics together identifies specific markers for each stress condition not detectable individually. Our findings provide insight into specific metabolic markers in plant responses to single and combined stresses, highlighting specific regulation of metabolic pathways, ion absorption, and physiological responses crucial for plant tolerance to climate change.

Highlight

The integration of different -omics has enabled the identification of specific ABA-dependent or –independent markers for single or combined abiotic stresses. These markers were not initially detectable when studying the different –omics individually.
Glycosaminoglycan-mediated lipoprotein uptake protects cancer cells from ferroptosis
Authors: Calhoon Dylan , Sang Lingjie , Bezwada Divya , Kim Nathaniel , Basu Amrita , Hsu Sheng-Chieh , Pimentel Anastasia , Brooks Bailey , La Konnor , Serrano Ana Paulina , Cassidy Daniel L. , Cai Ling , Toffessi-Tcheuyap Vanina , Margulis Vitaly , Cai Feng , Brugarolas James , Weiss Ryan J. , DeBerardinis Ralph J. , Birsoy Kıvanç , Garcia-Bermudez Javier
Published: May 2024

Lipids are essential for tumours because of their structural, energetic, and signaling roles. While many cancer cells upregulate lipid synthesis, growing evidence suggests that tumours simultaneously intensify the uptake of circulating lipids carried by lipoproteins. Which mechanisms promote the uptake of extracellular lipids, and how this pool of lipids contributes to cancer progression, are poorly understood. Here, using functional genetic screens, we find that lipoprotein uptake confers resistance to lipid peroxidation and ferroptotic cell death. Lipoprotein supplementation robustly inhibits ferroptosis across numerous cancer types. Mechanistically, cancer cells take up lipoproteins through a pathway dependent on sulfated glycosaminoglycans (GAGs) linked to cell-surface proteoglycans. Tumour GAGs are a major determinant of the uptake of both low and high density lipoproteins. Impairment of glycosaminoglycan synthesis or acute degradation of surface GAGs decreases the uptake of lipoproteins, sensitizes cells to ferroptosis and reduces tumour growth in mice. We also find that human clear cell renal cell carcinomas, a distinctively lipid-rich tumour type, display elevated levels of lipoprotein-derived antioxidants and the GAG chondroitin sulfate than non-malignant human kidney. Altogether, our work identifies lipoprotein uptake as an essential anti-ferroptotic mechanism for cancer cells to overcome lipid oxidative stress in vivo, and reveals GAG biosynthesis as an unexpected mediator of this process.
Detection of ATTR aggregates in plasma of polyneuropathic ATTR-V30M amyloidosis patients
Authors: Pedretti Rose , Wang Lanie , Grodin Justin L. , Masri Ahmad , Kelly Jeffery , Saelices Lorena
Published: May 2024

ATTR amyloidosis is caused by the deposition of transthyretin amyloid fibrils in tissues often leading to organ failure and death. The clinical spectrum of this disease is highly diverse and dependent on many factors including the presence or absence of mutations within the transthyretin protein and/or an individual’s ancestry. The phenotypic variability of ATTR amyloidosis makes it difficult to diagnose, delaying treatment and worsening patient prognosis. Our lab has recently developed a peptide probe that detects transthyretin aggregates in plasma of ATTR amyloidosis patients with cardiomyopathy but has not been tested in plasma from polyneuropathic patients. Here we evaluate our probe in a cohort of Portuguese patients carrying the ATTR-V30M mutation and having no cardiac phenotype. We found that we could indeed detect aggregates in their plasma, and there appeared to be no relationship between the presence of aggregates and patient age or gender. Our work has broad implications on the pathobiology of ATTR amyloidosis and contribute to the validation of our probe as a novel detection tool for this disease.
Peroxiredoxin 2 Regulates DAF-16/FOXO Mediated Mitochondrial Remodelling in Response to Exercise that is Disrupted in Ageing
Authors: Xia Qin , Li Penglin , Casas-Martinez José C. , Miranda-Vizuete Antonio , McDermott Emma , Dockery Peter , Goljanek-Whysall Katarzyna , McDonagh Brian
Published: May 2024

Ageing is associated with mitochondrial dysfunction and increased oxidative stress. Exercise generates endogenous reactive oxygen species (ROS) and promotes rapid mitochondrial remodelling. We investigated the role of Peroxiredoxin 2 (PRDX-2) in mitochondrial adaptations to exercise and ageing usingCaenorhabditis elegansas a model system. PRDX-2 was required for the mitochondrial remodelling in response to exercise mediated by DAF-16 nuclear localisation. Employing an acute exercise and recovery cycle, we demonstrated exercise-induced mitochondrial ER contact sites (MERCS) assembly and mitochondrial remodelling dependent on PRDX-2 and DAF-16 signalling. There was increased mitochondrial fragmentation, elevated ROS and an altered redox state of PRDX-2, concomitant with impaired DAF-16 nuclear localisation during ageing. Similarly, theprdx-2mutant strain exhibited increased mitochondrial fragmentation and a failure to activate DAF-16 required for mitochondrial fusion. Collectively, our data highlight the critical role of PRDX-2 in orchestrating mitochondrial remodelling in response to a physiological stress by regulating DAF-16 nuclear localisation.

Graphical abstract

Highlights

Exercise generates ROS and promotes mitochondrial remodelling dependent on DAF-16.

Exercise induces mitochondrial ER contact site assembly and mitochondrial dynamics.

Ageing and loss of PRDX-2 results in disrupted mitochondrial fusion.

The redox state of PRDX-2 determines appropriate DAF-16 nuclear localisation.
Mechanism of nucleus-chloroplast communication by alternative promoter usage and stromules to establish photomorphogenesis in Arabidopsis
Authors: Lee Jae-Hyung , Doan Thu Minh , Senthilkumar Sandhya , Yoo Chan Yul
Published: May 2024

Interorganellar communication is essential for maintaining cellular and organellar functions and adapting to dynamic environmental changes in eukaryotic cells. In plants, light triggers photomorphogenic development, including chloroplast biogenesis and the inhibition of hypocotyl elongation, through photoreceptors such as the red/far-red-sensing phytochromes and their downstream signaling pathways. However, the mechanism of interorganellar crosstalk underlying photomorphogenesis remains elusive. Here, we investigate the role of light-regulated alternative promoter usage inNUCLEAR CONTROL OF PEP ACTIVITY(NCP), a gene encoding a phytochrome signaling component that is dual-localized to the nucleus and chloroplasts. The long transcript variant (NCP-L) is upregulated under high red light, while the short variant (NCP-S) predominates in dark or low red light conditions. This light-regulated alternative transcription initiation ofNCPis dependent on PHYTOCHROME-INTERACTING FACTORS (PIFs). The NCP-L isoform primarily localizes to chloroplasts, whereas the NCP-S isoform is found in the cytoplasm and nucleus. Notably, chloroplast-localized NCP-L translocates to the nucleus via stromules. Consequently, NCP-L, present in both chloroplasts and the nucleus, initiates chloroplast biogenesis and inhibits hypocotyl growth during photomorphogenesis, whereas NCP-S is nonfunctional and degraded by the 26S proteasome. Taken together, our findings elucidate the mechanisms by which light-regulatedNCPalternative promoter usage and NCP retrotranslocation via stromules control photomorphogenesis in Arabidopsis. These mechanisms provide insights into interorganellar communication, orchestrating organ-specific developmental processes in response to fluctuating light environments.
Mitochondrial DNA and the 641kb nuclear-mitochondrial DNA inArabidopsiscan be separated by their CpG methylation levels
Authors: Zhong Yuyang , Okuno Miki , Tsutsumi Nobuhiro , Arimura Shin-ichi
Published: May 2024

Methylation on the cytosine in plant mitochondrial DNA has been a controversial issue. Results supporting mitochondrial DNA methylation may have been subject to contamination due to the presence of the nuclear sequence originating from the mitochondrial genome called NUMT (nuclear mitochondrial DNA insertions). Especially inArabidopsis thalianaColumbia 0, the largest NUMT located on chromosome 2 is nearly twice the size of the entire mitochondrial genome and almost identical. In the presence of such high similarity, it is challenging to eliminate interference in the determination of mitochondrial DNA methylation levels. Here we applied MBD (methyl-CpG binding domain) protein-based affinity assay to separate total DNA, and applied next generation sequencing to the pre- and post-separation DNA samples, and checked their SNP sites. The results revealed successful separation of methylated and non-methylated DNA within the total DNA, with separation achieved between NUMT DNA and mitochondrial DNA. The result suggests that our method can achieve separation based on the differential methylation levels of the whole lengths of NUMT and mitochondrial DNAs, and that mitochondrial DNA barely exhibits CpG methylation, at least in the Columbia 0.
Peripheral Nerve Crush inDrosophilaLarvae
Authors: Waller Thomas J. , Smithson Laura J. , Collins Catherine A.
Published: May 2024

The long length of axons makes them vulnerable to damage; hence, it is logical that nervous systems have evolved adaptive mechanisms for responding to axon damage. Studies inDrosophila melanogasterhave identified evolutionarily conserved molecular pathways that enable axonal degeneration and regeneration of damaged axons and/or dendrites. This protocol describes a simple method for inducing nerve crush injury to motoneuron and sensory neuron axons in the peripheral (segmental) nerves in second- or early third-instar larvae. Small forceps are used to pinch the cuticle at a location that overlays the segmental nerves. Although the connective tissue of the nerves remains intact and the larva survives the injury, single motoneuron and sensory neuron axons incur a break in continuity at the damage site and then undergo Wallerian degeneration distal to the break. This degeneration includes the dismantling of neuromuscular junction (NMJ) synapses formed by the axons that incurred damage. With stereotyped anatomy and accessibility to structural and electrophysiological studies, the larval NMJ is a good model to characterize the cellular changes that occur in synapses undergoing degeneration and to identify conditions that can protect axons and synapses from degeneration.
Measuring the Readily Releasable Synaptic Vesicle Pool at theDrosophilaLarval Neuromuscular Junction
Authors: Wang Tingting , Frank C. Andrew
Published: May 2024

Presynaptic homeostatic potentiation (PHP) is a type of homeostatic regulation that stabilizes synaptic output under conditions where postsynaptic receptor function is impaired. PHP manifests as a significant increase in presynaptic neurotransmitter release, compensating for decreased postsynaptic receptor activity and thus maintaining stable excitation levels in postsynaptic cells. Presynaptic neurotransmitter release is calcium-dependent, initiated by calcium influx through voltage-gated calcium channels localized at the presynaptic active zones. This calcium influx triggers the fusion of vesicles from the readily releasable vesicle pool (RRP) that are ready for immediate release. Two key presynaptic cellular mechanisms are essential for PHP's induction and maintenance. First, a compensatory rise in the abundance of presynaptic calcium channels (and consequently, an increase in calcium influx) occurs when postsynaptic glutamate receptors are suppressed. Second, the RRP size enlarges during PHP. PHP is disrupted if either of these processes is impaired. This protocol outlines the use of the two-electrode voltage-clamp technique for assessing the RRP during PHP, induced either pharmacologically or genetically, at theDrosophilaneuromuscular junction (NMJ). Electrophysiological recordings typically take place at the NMJ of muscle 6 in abdominal segments A2 and A3.
Imaging Neuropeptide Release fromDrosophilaClock and Motor Neurons
Authors: Levitan Edwin S. , Bulgari Dinara , Klose Markus K.
Published: May 2024

Electrophysiological studies of synaptic function do not robustly report release of neuropeptides and neurotrophins. These limitations have been overcome with the presynaptic expression of optical release reporters based on green fluorescent protein and fluorogen-activating protein. Here we describe how to image neuropeptide release inDrosophilaat the neuromuscular junction and in the adult brain.
Almost gauge-invariant states and the ground state of Yang-Mills theory
Authors: Mariani A.
Published: May 2024

We consider the problem of the explicit description of the gauge-invariant subspace of pure lattice gauge theories in the Hamiltonian formulation, where the gauge group is either a compact Lie group or a finite group. The latter case is particularly interesting for quantum simulation. A basis of states where configurations are grouped according to their holonomies is shown to have several advantages over other descriptions. Using this basis, we compute some properties of interest for some non-Abelian finite groups on small lattices, and in particular we examine the question of whether a certain ansatz introduced long ago is a good approximation for the ground state.

Published by the American Physical Society
2024
Study of a cubic cavity resonator for gravitational waves detection in the microwave frequency range
Authors: Navarro Pablo , Gimeno Benito , Monzó-Cabrera Juan , Díaz-Morcillo Alejandro , Blas Diego
Published: May 2024

The direct detection of gravitational waves (GWs) of frequencies above MHz has recently received considerable attention. In this work, we present a precise study of the reach of a cubic cavity resonator to GWs in the microwave range, using for the first time tools allowing to perform realistic simulations. Concretely, the boundary integral—resonant mode expansion (BI-RME) 3D method, which allows us to obtain not only the detected power but also the detected voltage (magnitude and phase), is used here. After analyzing three cubic cavities for different frequencies and working simultaneously with three different degenerate modes at each cavity, we conclude that the sensitivity of the experiment is strongly dependent on the polarization and incidence angle of the GW. The presented experiment can reach sensitivities up to 1×10−19 at 100 MHz, 2×10−20 at 1 GHz, and 6×10−19 at 10 GHz for optimal angles and polarizations, and where in all cases we assumed an integration time of Δt=1  ms. These results provide a strong case for further developing the use of cavities to detect GWs. Moreover, the possibility of analyzing the detected voltage (magnitude and phase) opens a new interferometric detection scheme based on the combination of the detected signals from multiple cavities.

Published by the American Physical Society
2024
Partially celestial states and their scattering amplitudes
Authors: Csáki Csaba , Telem Ofri , Terning John
Published: May 2024

We study representations of the Poincaré group that have a privileged transformation law along a p-dimensional hyperplane, and uncover their associated spinor-helicity variables in D spacetime dimensions. Our novel representations generalize the recently introduced celestial states and transform as conformal primaries of SO(p,1), the symmetry group of the p-hyperplane. We will refer to our generalized states as “partially celestial.” Following Wigner’s method, we find the induced representations, including spin degrees of freedom. Defining generalized spinor-helicity variables for every D and p, we are able to construct the little group covariant part of partially celestial amplitudes. Finally, we briefly examine the application of the pairwise little group to partially celestial states with mutually nonlocal charges.

Published by the American Physical Society
2024
Emergent Noninvertible Symmetries in
N=4
Supersymmetric Yang-Mills Theory
Authors: Sela Orr
Published: May 2024

One of the simplest examples of noninvertible symmetries in higher dimensions appears in 4D Maxwell theory, where its SL(2,Z) duality group can be combined with gauging subgroups of its electric and magnetic 1-form symmetries to yield such defects at many different values of the coupling. Even though N=4 supersymmetric Yang-Mills (SYM) theory also has an SL(2,Z) duality group, it only seems to share two types of such noninvertible defects with Maxwell theory (known as duality and triality defects). Motivated by this apparent difference, we begin our investigation of the fate of these symmetries by studying the case of 4D N=4 U(1) gauge theory, which contains Maxwell theory in its content. Surprisingly, we find that the noninvertible defects of Maxwell theory give rise, when combined with the standard U(1) symmetry acting on the free fermions, to defects that act on local operators as elements of the U(1) outer automorphism of the N=4 superconformal algebra, an operation that was referred to in the past as the “bonus symmetry.” Turning to the non-Abelian case of N=4 SYM theory, the bonus symmetry is not an exact symmetry of the theory, but is known to emerge at the supergravity limit. Based on this observation, we study this limit and show that, if it is taken in a certain way, noninvertible defects that realize different elements of the bonus symmetry emerge as approximate symmetries, in analogy to the Abelian case.

Published by the American Physical Society
2024
Bound Isoscalar Axial-Vector
bcu¯d¯
Tetraquark
Tbc
from Lattice QCD Using Two-Meson and Diquark-Antidiquark Variational Basis
Authors: Padmanath M. , Radhakrishnan Archana , Mathur Nilmani
Published: May 2024

We report a lattice QCD study of the heavy-light meson-meson interactions with an explicitly exotic flavor content bcu¯d¯, isospin I=0, and axial-vector JP=1+ quantum numbers in search of possible tetraquark bound states. The calculation is performed at four values of lattice spacing, ranging from ∼0.058 to ∼0.12  fm, and at five different values of valence light quark mass mu/d, corresponding to pseudoscalar meson mass Mps of about 0.5, 0.6, 0.7, 1.0, and 3.0 GeV. The energy eigenvalues in the finite volume are determined through a variational procedure applied to correlation matrices built out of two-meson interpolating operators as well as diquark-antidiquark operators. The continuum limit estimates for DB¯* elastic S-wave scattering amplitude are extracted from the lowest finite-volume eigenenergies, corresponding to the ground states, using amplitude parametrizations supplemented by a lattice spacing dependence. Light quark mass mu/d dependence of the DB¯* scattering length (a0) suggests that at the physical pion mass a0phys=+0.57(−5+4)(17)  fm, which clearly points to an attractive interaction between the D and B¯* mesons that is strong enough to host a real bound state Tbc, with a binding energy of −43(−7+6)(−24+14)  MeV with respect to the DB¯* threshold. We also find that the strength of the binding decreases with increasing mu/d and the system becomes unbound at a critical light quark mass mu/d* corresponding to Mps*=2.73(21)(19)  GeV.

Published by the American Physical Society
2024
Work statistics for quantum spin chains: Characterizing quantum phase transitions, benchmarking time evolution, and examining passivity of quantum states
Authors: Lin Feng-Li , Huang Ching-Yu
Published: May 2024

We study three aspects of work statistics in the context of the fluctuation theorem for quantum spin chains up to 1024 sites by numerical methods based on matrix-product states (MPSs). First, we use our numerical method to evaluate the moments/cumulants of work done by the sudden quench process on the Ising or Haldane spin chains, and we study their behaviors across the quantum phase transitions. Our results show that, up to the fourth cumulant, the work statistics can indicate the quantum phase transition characterized by the local order parameters but barely for purely topological phase transitions. Second, we propose to use the fluctuation theorem, such as Jarzynski's equality, which relates the real-time correlator to the ratio of the thermal partition functions, as a benchmark indicator for the numerical real-time evolving methods. Third, we study the passivity of ground and thermal states of quantum spin chains under some cyclic impulse processes. We show that the passivity of thermal states and ground states under the Hermitian actions is ensured by the second laws and variational principles, respectively, and we also verify this by numerical calculations. In addition, we also consider the passivity of ground states under non-Hermitian actions, for which the variational principle cannot be applied. Despite that, we find no violation of passivity from our numerical results for all the cases considered in the Ising and Haldane chains. Overall, we demonstrate that the work statistics for the sudden quench and impulse processes can be evaluated precisely by the numerical MPS method to characterize quantum phase transitions and examine the passivity of quantum states. We also propose to exploit the universality of the fluctuation theorem to benchmark the numerical real-time evolutions in an algorithmic and model-independent way.

Published by the American Physical Society
2024
Sensing Coherent Nuclear Spin Dynamics with an Ensemble of Paramagnetic Nitrogen Spins
Authors: Goldblatt R.M. , Martin A.M. , Wood A.A.
Published: May 2024

The unpolarized spin environment surrounding a central spin qubit is typically considered as an incoherent source of dephasing, however, precise characterization and control of the spin bath can yield a resource for storing and sensing with quantum states. In this work, we use nitrogen-vacancy (NV) centers in diamond to measure the coherence of optically dark paramagnetic nitrogen defects (P1 centers) and detect coherent interactions between the P1 centers and a local bath of 13C nuclear spins. The dipolar coupling between the P1 centers and 13C nuclear spins is identified by signature periodic collapses and revivals in the P1 spin coherence signal. We then demonstrate, using a range of dynamical decoupling protocols, that the probing NV centers and the P1 spins are coupled to independent ensembles of 13C nuclear spins. Our work illustrates how the optically dark P1 spins can be used to extract information from their local environment and offers new insight into the interactions within a many-body system.

Published by the American Physical Society
2024
“A war waged with numbers”: Accounting and accumulation by alienation in Australia’s border industrial complex
Authors: Scobie Matthew , Laird Lila
Published: May 2024

Purpose

This paper explores the role of accounting and accountability techniques in contributing to Australia’s border industrial complex.

Design/methodology/approach

We use the political thought of Behrouz Boochani to explore the role that accounting techniques play at the micro and macro level of his dialectic of alienation and freedom. Firstly, we explore the accounting and accountability techniques detailed in Boochani’s No Friend but the Mountain, which gives an account of his life in Manus Prison, and the accounting techniques he experienced. Secondly, we explore the discourse of alienation created within the annual reporting of the Australian Federal Government regarding the border industrial complex.

Findings

We argue that the border industrial complex requires the alienation of asylum seekers from their own humanity for capital accumulation, and that accounting and accountability techniques facilitate this form of alienation. These techniques include inventorying, logging and queuing at the micro level within Manus Prison. This alienates those trapped in the system from one another and themselves. Techniques also include annual reporting at a macro level which alienates those trapped in the system from the (White) “Australian Community”. However, these techniques are resisted at every point by assertions of freedom.

Originality/value

We illustrate the role of accounting in accumulation by alienation, where the unfreedom of incarcerated asylum seekers is a site of profit for vested interests. But also that this alienation is resisted at every point by refusals of alienation as assertions of freedom. Thus, this study contributes to the accounting literature by drawing from theories of alienation, and putting forward the dialectic of alienation and freedom articulated by Boochani and collaborators.
A qualitative exploration of female professors’ promotion trajectories in public universities in Pakistan
Authors: Sadaf Fouzia , Bano Shermeen , Rahat Rahla
Published: May 2024

Purpose

The central aim of this study is to advance understanding of the influence of university practices and structures on shaping female academics’ paths to reach the position of professor in Pakistan.

Design/methodology/approach

About 30 qualitative, semi-structured interviews were conducted with female professors to examine key enablers and barriers to their promotion trajectories towards reaching the position of professor in public universities in Punjab, Pakistan.

Findings

This study presents an analysis of promotion biographies and has identified a combination of personal, interpersonal and structural factors as enablers and barriers to the promotion trajectory from junior academic positions to the level of professorship among female professors in public universities in Pakistan. Three main kinds of promotion trajectories were identified, which represent three different configurations of elements relating to (1) personal credentials and strategies to manage delays, (2) workplace relations and (3) university promotion systems.

Originality/value

The findings of this research may be helpful in terms of (1) offering ideas regarding support for women who are making career decisions and achieving inspiring successful careers; (2) informing university governance to address the barriers that curtail women’s accomplishment of their career goals and (3) devising/improving strategic plans to address the entrenched gender disparity in academic leadership and broader society.
Gender differences in executive compensation in Spain
Authors: Nagore Amparo , García Martín Constantino José
Published: May 2024

Purpose

In the context of sustainable development goal 5 of the United Nations 2030 Agenda: “Achieve gender equality and women’s empowerment”, where gender equality is not only a matter of justice but also essential to achieve sustainable development, this paper aims to examine the gender pay gap in executive director compensation and the influence of female board representation and participation in nomination and remuneration committee (NRC) on this gap in Spanish listed firms over the period 2012–2022.

Design/methodology/approach

The analysis is conducted using a data set created by the authors, which includes executive director compensation data for 164 unique firms. This data set comprises 128 distinct observations for a given firm and year for women, and 2,333 observations for men. The authors estimate ordinary least squares models, clustering standard errors by executive. The authors use Oaxaca-Blinder decomposition to decompose gender differences in compensation into differences in the characteristics of men and women and differences in the return on the same characteristics.

Findings

The authors find evidence of pay penalty for female executive directors compared to male counterparts. After controlling for firm, board and executive characteristics, the authors find that women earn 27% less than comparable men. The penalty is lower in companies with a higher share of women on the compensation committee, suggesting that women’s participation plays a role in setting a more equal remuneration policy. The gender gap in executive compensation narrows over time due to a substantial reduction of the differences between men and women in both characteristics and the return on these characteristics.

Originality/value

This study is one of the few analysing the gender gap in executive director compensation and its evolution in Spain. It specifically explores how gender diversity on both the board and the NRC impacts this gap. The analysis is focused on the most recent period characterized by important efforts to promote gender diversity.