bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiological and Molecular Responses of Projected Future Temperatures on Potato Tuberization
Authors: Guillemette Abigail M. , Casanova Guillian Hernández , Hamilton John P. , Pokorná Eva , Dobrev Petre I. , Motyka Václav , Rashotte Aaron M. , Leisner Courtney P. 
Published: August 2024

AbstractPotato (Solanum tuberosumL.) is one of the most important food crops globally and is especially vulnerable to heat stress. Significant knowledge gaps remain however, in our understanding of the developmental mechanisms associated with tuber responses to heat stress. This study uses whole-plant physiology, transcriptomics, and hormone profiling to gain insights into the mechanisms associated with heat stress impacts on potato tuber development. When plants were grown in projected future temperature conditions, levels of abscisic acid (ABA) were significantly decreased in leaf and tuber tissues while rates of leaf carbon assimilation and stomatal conductance were not significantly affected. While plants grown in elevated temperature conditions initiated more tubers on average per plant, there was a significant decrease (66%) in mature tubers at final harvest. We hypothesize that reduced tuber yields at elevated temperatures are not due to reductions in tuber initiation, but due to impaired tuber filling. Transcriptomic analysis found significant changes in transcript expression for genes related to response to ABA, heat and auxin biosynthetic process. The known tuberization repressor genes SELF PRUNING 5G (StSP5G) and CONSTANS-LIKE1 (StCOL1) were found to be differentially expressed in tubers grown in elevated temperatures. IDENTITY OF TUBER 1 (StIT1) and TIMING OF CAB EXPRESSION 1 (StTOC1) are other known tuberization genes that displayed distinct expression patterns in elevated versus ambient temperatures but were not differentially expressed. This work highlights potential gene targets and key developmental stages associated with tuberization to development more heat tolerant potatoes.
Mastering Artifact Correction in Neuroimaging Analysis: A Retrospective Approach
Authors: Oliveira Alícia , Cepa Beatriz , Brito Cláudia , Sousa António 
Published: August 2024

AbstractThe correction of artifacts in Magnetic Resonance Imaging (MRI) is increasingly relevant as voluntary and involuntary artifacts can hinder data acquisition. Reverting from corrupted to artifact-free images is a complex task. Deep Learning (DL) models have been employed to preserve data characteristics and to identify and correct those artifacts. We proposeMOANA, a novel DL-based solution to correct artifacts in multi-contrast brain MRI scans.MOANAoffers two models: the simulation and the correction models. The simulation model introduces perturbations similar to those occurring in an exam while preserving the original image as ground truth; this is required as publicly available datasets rarely have motion-corrupted images. It allows the addition of three types of artifacts with different degrees of severity. The DL-based correction model adds a fourth contrast to state-of-the-art solutions while im-proving the overall performance of the models.MOANAachieved the highest results in the FLAIR contrast, with a Structural Similarity Index Measure (SSIM) of 0.9803 and a Normalized Mutual Information (NMI) of 0.8030. With this, theMOANAmodel can correct large volumes of images in less time and adapt to different levels of artifact severity, allowing for better diagnosis.
The intrinsic dimension of gene expression during cell differentiation
Authors: Biondo Marta , Cirone Niccolò , Valle Filippo , Lazzardi Silvia , Caselle Michele , Osella Matteo 
Published: August 2024

AbstractWaddington’s epigenetic landscape has long served as a conceptual framework for understanding cell fate decisions. The landscape’s geometry encodes the molecular mechanisms that guide the gene expression profiles of uncommitted cells toward terminally differentiated cell types. In this study, we demonstrate that applying the concept of intrinsic dimension to single-cell transcriptomic data can effectively capture trends in expression trajectories, supporting this framework. This approach allows us to define a robust cell potency score without relying on prior biological information. By analyzing an extensive collection of datasets from various species, experimental protocols, and differentiation processes, we validate our method and successfully reproduce established hierarchies of cell type potency.
Paradoxical SERCA dysregulation contributes to atrial fibrillation in a model of diet-induced obesity
Authors: Ponce-Balbuena Daniela , Tyrrell Daniel J. , Cruz-Cortés Carlos , Guerrero-Serna Guadalupe , Da Rocha Andre Monteiro , Herron Todd J. , Song Jianrui , Raza Danyal S. , Anumonwo Justus , Goldstein Daniel R. , Espinoza-Fonseca L. Michel 
Published: August 2024

AbstractObesity is a major risk factor for atrial fibrillation (AF) the most common serious cardiac arrhythmia, but the molecular mechanisms underlying diet-induced AF remain unclear. In this study, we subjected mice to a chronic high-fat diet and acute sympathetic activation (‘two-hit’ model) to study the mechanisms by which diet-induced obesity promotes AF. Surface electrocardiography revealed that diet-induced obesity and sympathetic activation synergize during intracardiac tachypacing to induce AF. At the cellular level, diet-induced obesity and acute adrenergic stimulation facilitate the formation of delayed afterdepolarizations in atrial myocytes, implicating altered Ca2+dynamics as the underlying cause of AF. We found that diet-induced obesity does not alter the expression of major Ca2+-handling proteins in atria, including the sarcoplasmic reticulum Ca2+-ATPase (SERCA), a major component of beat-to-beat Ca2+cycling in the heart. Paradoxically, obesity reduces phospholamban phosphorylation, suggesting decreased SERCA activity, yet atrial myocytes from obese mice showed a significantly increased Ca2+transient amplitude and SERCA-mediated Ca2+uptake. Adrenergic stimulation further increases the Ca2+transient amplitude but does not affect Ca2+reuptake in atrial myocytes from obese mice. Transcriptomics analysis showed that a high-fat diet prompts upregulation of neuronatin, a protein that has been implicated in obesity and is known to stimulate SERCA activity. We propose a mechanism in which obesity primes SERCA for paradoxical activation, and adrenergic stimulation facilitates AF conversion through a Ca2+-induced Ca2+release gain in atrial myocytes. Overall, this study links obesity, altered Ca2+signaling, and AF, and targeting this mechanism may prove effective for treating obesity-induced AF.
OXPHOS TARGETING OF MYCN-AMPLIFIED NEUROBLASTOMA
Authors: Epp Soraya , Egan Donagh , Poon Evon , Abdul Aziz Amirah Adlina , Wynne Kieran , Halasz Melinda , Kolch Walter 
Published: August 2024

Abstract/SummaryHigh risk - neuroblastoma (HR-NB) is a pediatric solid tumor with high lethality. Half of HR-NB are driven by MYCN gene amplification (MNA). These HR-NBs require high dosage chemotherapy and often relapse. Moreover, current therapies can cause severe long-term side effects and new therapies are urgently needed. This study investigates a novel therapeutic approach targeting the metabolic vulnerabilities of MNA NB cells. We discovered that Diphenyleneiodonium chloride (DPI), an inhibitor of flavoprotein enzymes and mitochondrial complex I, synergizes with mitoquinone mesylate (MitoQ), a mitochondria-targeted antioxidant in 2D and 3Din vitromodels of NB. Similarly to DPI, MitoQ affects MNA cells in a MYCN-dependent way, being more toxic when MYCN levels are high. Furthermore, low nanomolar concentrations of MitoQ significantly decrease MYCN protein expression and induce differentiation of MNA cells. The DPI and MitoQ combination further synergizes with vincristine, a chemotherapeutic agent used in NB treatment. Phosphoproteomics and proteomics analysis suggests that the drug combination induces MNA NB cell death by arresting the cell cycle and inhibiting oxidative phosphorylation (OXPHOS) in the mitochondria. Thus, interference with mitochondrial metabolism may represent an effective strategy to enhance the activity of chemotherapeutic drugs in MNA-NB.
VSTM2L protects prostate cancer cells against ferroptosis via inhibiting VDAC1 oligomerization and maintaining mitochondria homeostasis
Authors: Yang Juan , Lu Xiao , Hao Jing-Lan , Li Lan , Ruan Yong-Tong , An Xue-Ni , Dong Xiao-Ming , Gao Ping 
Published: August 2024

ABSTRACTMitochondria play a critical role in initiating and amplifying ferroptosis. VDAC1 embedded in the mitochondrial outer membrane, exerts a crucial role in regulation of ferroptosis. However, the mechanisms of VDAC1 oligomerization in regulating ferroptosis are not well elucidated. Here, we identified that VSTM2L, a novel VDAC1 binding protein, is positively associated with prostate cancer (PCa) progression, and a key regulator of ferroptosis. Moreover, VSTM2L knockdown in PCa cells enhanced the sensibility of RSL3-induced ferroptosis. Mechanistically, VSTM2L forms complex with VDAC1 and HK2, enhancing their binding affinity and preventing VDAC1 oligomerization, thereby inhibiting ferroptosis and maintaining mitochondria homeostasisin vitroandin vivo. Collectively, our findings reveal a pivotal role for VSTM2L in driving ferroptosis resistance and highlight its potential as a ferroptosis-inducing therapeutic target for the treatment of PCa.
WITHDRAWN: A preliminary investigation of a soluble dietary fibre and mineral formulation on post-prandial glucose regulation and satiation
Authors: Haynes Michael 
Published: August 2024

Withdrawal statementThe authors have withdrawn this manuscript because of conflicts of interest. This involves coauthor contributions and Optibiotix awareness/ agreement for their product use in this study. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
From messy chemistry to ecology: autocatalysis and heritability in prebiotically plausible chemical systems
Authors: Sokolskyi Tymofii , Zuviria Bruno Cuevas , Gargulak Sydney , Allen Esau , Baum David 
Published: August 2024

AbstractA key question in origins-of-life research, is whether heritability, and thus evolution, could have preceded genes. Out-of-equilibrium chemical reaction networks with multiple autocatalytic motifs may provide chemical “memory” and serve as units of heritability, but experimental validation is lacking. We established conditions that may be conducive to the emergence of heritable variation and developed methods to search for heritability and autocatalysis. We prepared a food set (FS) of three organic species, three inorganic salts and pyrite. We conducted a serial dilution experiment where FS was incubated for 24 hours, after which a 20% fraction was transferred into freshly prepared FS that went through the same procedure, repeated for 10 generations. To serve as controls, we also incubated the fresh solutions in each generation. We compared the chemical composition of transfer vials and no-transfer controls using liquid chromatography-mass spectrometry (LCMS), with metrics adapted from ecology and evolutionary biology. While variability was high, focusing on a subset of chemicals with more consistent patterns revealed evidence of heritable variation among vials. Using rule-based chemical reaction network inference, constrained by the LCMS data, we identified a plausible FS-driven chemical reaction network that was found to contain numerous autocatalytic cycles.
From Virtual Screens to Cellular Target Engagement: New Small Molecule Ligands for the Immune Checkpoint LAG-3
Authors: Fuchs Natalie , Calvo-Barreiro Laura , Talagayev Valerij , Pach Szymon , Wolber Gerhard , Gabr Moustafa T. 
Published: August 2024

ABSTRACTHerein, we performed a virtual screening study to discover new scaffolds for small molecule-based ligands of the immune checkpoint lymphocyte-activation gene 3 (LAG-3). Molecular dynamics (MD) simulations using the LAG-3 structure revealed two putative binding sites for small molecules: the antibody interface and a lipophilic canyon. A 3D pharmacophore screening resulted in the identification of potential ligands for these binding sites and afforded a library of 25 compounds. We then evaluated the screening hits for LAG-3 binding via microscale thermophoresis (MST) and surface plasmon resonance (SPR). Our biophysical screening identified two binders withKDvalues in the low micromolar range, compounds 3 (antibody interface) and25(lipophilic canyon). Furthermore, we investigated the ability of LAG-3 hits to en-gage LAG-3 on a cellular level using a cellular thermal shift assay (CETSA), where compound3emerged as a promising candidate for future development.
ERBB2/HOXB13co-amplification with interstitial deletion ofBRCA1defines a unique subset of breast cancers
Authors: Mitsiades Irene Rin , Onozato Maristela , John Iafrate A. , Hicks Daniel , Sgroi Dennis C. , Rheinbay Esther 
Published: August 2024

AbstractBackgroundTheHOXB13/IL17BRgene expression biomarker has been shown to predict response to adjuvant and extended endocrine therapy in patients with early-stage ER+ HER2- breast tumors.HOXB13gene expression is the primary determinant driving the prognostic and endocrine treatment-predictive performance of the biomarker. Currently, there is limited data onHOXB13expression in HER2+ and ER- breast cancers. Herein, we studied the expression ofHOXB13in large cohorts of HER2+ and ER- breast cancers.MethodsWe investigated gene expression, genomic copy number, mutational signatures, and clinical outcome data in the TGGA and METABRIC breast cancer cohorts. Genomic-based gene amplification data was validated with tri-colored fluorescencein situhybridization.ResultsIn the TCGA breast cancer cohort,HOXB13gene expression was significantly higher in HER2+ versus HER2- breast cancers, and its expression was also significantly higher in the ER- versus ER+ breast cancers.HOXB13is frequently co-gained or co-amplified withERBB2. Joint copy gains ofHOXB13andERBB2occurred with low-level co-gains or high-level co-amplifications (co-amp), the latter of which is associated with an interstitial deletion that includes the tumor suppressorBRCA1.ERBB2/HOXB13co-amp tumors with interstitialBRCA1loss exhibit a mutational signature associated with APOBEC deaminase activity, and copy number signatures associated with chromothripsis and genomic instability. AmongERBB2-amplified tumors of different tissue origins,ERBB2/HOXB13co-amp with aBRCA1loss appeared to be unique to breast cancer. Lastly, patients withERBB2/HOXB13co-amplified andBRCA1lost tumors displayed a significantly shorter progression-free survival (PFS) than those withERBB2-only amplifications. The difference in PFS was restricted to the ER- subset patients and this difference in PFS was not solely driven byHOXB13gene expression.ConclusionsHOXB13is frequently co-gained withERBB2at both low-copy number level or as complex high-level amplification with relativeBRCA1loss.ERBB2/HOXB13amplified,BRCA1-lost tumors are strongly enriched in breast cancer, and patients with such breast tumors experience a shortened PFS.
TAM receptors mediate the Fpr2-driven pain resolution and fibrinolysis after nerve injury
Authors: Hartmannsberger Beate , Ben-Kraiem Adel , Kramer Sofia , Guidolin Carolina , Kazerani Ida , Doppler Kathrin , Thomas Dominique , Gurke Robert , Sisignano Marco , Kalelkar Pranav P. , García Andrés J. , Monje Paula V. , Nusrat Asma , Brack Alexander , Krug Susanne M. , Sommer Claudia , Rittner Heike L. 
Published: August 2024

AbstractNerve injury causes neuropathic pain and multilevel nerve barrier disruption. Nerve barriers consist of perineurial, endothelial, and myelin barriers. So far, it is unclear whether resealing nerve barriers fosters pain resolution and recovery. To this end, we analysed the nerve barrier property portfolio, pain behaviour battery, and lipidomics for precursors of specialized pro-resolving meditators (SPMs) and their receptors in chronic constriction injury of rat sciatic nerve to identify targets for pain resolution by resealing the selected nerve barriers. Of the three nerve barriers – perineurium, capillaries, and myelin – only capillary tightness specifically against larger molecules, such as fibrinogen, recuperated with pain resolution. Fibrinogen immunoreactivity was not only elevated in rats at the time of neuropathic pain but also in nerve biopsies from patients with (but not without) painful polyneuropathy indicating that sealing of the vascular barrier might be novel approach in pain treatment. 15R-HETE (hydroxyeicosatetraenoic acid), a precursor of aspirin-triggered lipoxin A4, were specifically upregulated at the beginning of pain resolution. Repeated local application of resolvin D1-laden nanoparticles or Fpr2 agonists sex-independently resulted in accelerated pain resolution and fibrinogen removal. Clearing macrophages (Cd206)and fibrinolytic pathways (Plat)were also induced while inflammation (Tnfα)and inflammasomes (Nlrp3)were unaffected by this treatment. Blocking TAM receptors (Tyro3, Axl, and Mer) and tyrosine kinase receptors linking haemostasis and inflammation completely inhibited all the effects. In summary, nanoparticles can be used as transporters for fleeting lipids, such as SPMs, and therefore expand the array of possible therapeutic agents. Thus, the Fpr2-Cd206-TAM receptor axis may be a suitable target for strengthening the capillary barrier, removing endoneurial fibrinogen, and boosting pain resolution in patients with chronic neuropathic pain.
A Small Interfering Peptide Potentiates AMPA Receptor Diffusional Trapping and Prevents Social-Isolation-Induced Forgetting of Fear Memory
Authors: Gundersen Jens Edvard Trygstad , Wu Xinrong , Song Jiaxing , Yao Jingyu , Nesbø Håvard Håvardsholm , Pokharna Aditya , Mergiya Tadiwos Feyissa , Liu Huadong , Sun Suya , Greger Ingo , Wang Changhe , Xu Nan-jie , Bramam Clive R , Zhang Hongyu 
Published: August 2024

AbstractRegulation and dysregulation of AMPA receptor (AMPAR) diffusional trapping at synapses are critical for synaptic efficacy and are implicated in various neurological and neuropsychiatric disorders. However, the limited availability of reliable tools to modulate this process hinders our ability to explore its role in both physiological conditions and disease, as well as in drug development. In this study, we designed and characterized a 21-amino-acid trans-activator of transcription (TAT)-fused peptide that mimics the binding region of the transmembrane AMPAR regulatory proteins (TARPs) C-tail to the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) N-lobe. Acute intrahippocampal infusion of this peptide enhanced perforant path-evoked synaptic transmission in the rat dentate gyrus (DG) in vivo, likely by strengthening the interaction between TARP and postsynaptic density protein 95 (PSD-95), a mechanism crucial for the synaptic anchoring of AMPARs. Additionally, the peptide also slowed AMPAR lateral diffusion and blocked KCl-induced AMPAR endocytosis, likely by enhancing the diffusional trapping of AMPARs at the synapse. Remarkably, a 7-day peptide infusion prevented social-isolation-induced forgetting of fear memory. Our findings suggest that targeting AMPAR diffusional trapping, particularly through disrupting the TARP-Arc N-lobe interaction, could hold promise as a therapeutic approach for neurological and neuropsychiatric disorders associated with impaired AMPAR synaptic retention.
Twisted Sister1: an agravitropic mutant of bread wheat (Triticum aestivum) with altered root and shoot architectures
Authors: Zeng Deying , Peng Jiayu , Zhang Lan , Hayden Mathew J. , Rathjen Tina M. , Zhu Bo , Zeng Zixian , Delhaize Emmanuel 
Published: August 2024

AbstractWe identified a mutant of hexaploid wheat (Triticum aestivum) with impaired responses to gravity. The mutant namedTwisted Sister1(TS1) had agravitropic roots that were often twisted along with altered shoot phenotypes. Roots ofTS1were insensitive of externally applied auxin with the genetics and physiology suggestive of a mutatedAUX/IAAtranscription factor gene. Hexaploid wheat possesses over eightyAUX/IAAgenes and sequence information did not identify an obvious candidate. Bulked segregant analysis of an F2population mapped the mutation to chromosome 5A and subsequent mapping located the mutation to a 41 Mbp region. RNA-seq identified theTraesCS5A03G0149800gene encoding a TaAUX/IAA protein to be mutated in the highly conserved domain II motif. We confirmedTraesCS5A03G0149800as underlying the mutant phenotype by generating transgenicArabidopsis thaliana. Analysis of RNA-seq data suggested broad similarities between Arabidopsis and wheat for the role ofAUX/IAAgenes in gravity responses. Here we show that the sequenced wheat genome along with previous knowledge largely from the model species Arabidopsis, gene mapping, RNA-seq and expression in Arabidopsis have enabled cloning of a key wheat gene defining plant architecture.
Learning in single cells: biochemically-plausible models of habituation
Authors: Eckert Lina , Vidal-Saez Maria Sol , Zhao Ziyuan , Garcia-Ojalvo Jordi , Martinez-Corral Rosa , Gunawardena Jeremy 
Published: August 2024

AbstractThe ability to learn is typically attributed to animals with brains. However, the apparently simplest form of learning, habituation, in which a steadily decreasing response is exhibited to a repeated stimulus, is found not only in animals but also in single-cell organisms and individual mammalian cells. Habituation has been codified from studies in both invertebrate and vertebrate animals, as having ten characteristic hallmarks, seven of which involve a single stimulus. Here, we show by mathematical modelling that simple molecular networks, based on plausible biochemistry with common motifs of negative feedback and incoherent feedforward, can robustly exhibit all single-stimulus hallmarks. The models reveal how the hallmarks arise from underlying properties of timescale separation and reversal behaviour of memory variables and they reconcile opposing views of frequency and intensity sensitivity expressed within the neuroscience and cognitive science traditions. Our results suggest that individual cells may exhibit habituation behaviour as rich as that in multi-cellular animals with central nervous systems and that the relative simplicity of the biomolecular level may enhance our understanding of the mechanisms of learning.