bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractExtreme 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

AbstractBackground and purposeTimely 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 methodsWe 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.ResultsThe 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%.ConclusionIntegrating 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 StatementOur 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

AbstractThe 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.
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

AbstractEpstein-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 SummaryEpstein-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

AbstractOver 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.HighlightThe 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

ABSTRACTLipids 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

AbstractATTR 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

AbstractAgeing 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 abstractHighlightsExercise 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

AbstractInterorganellar 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

AbstractMethylation 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.
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
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