bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects and phenotypic consequences of transient thyrotoxicosis and hypothyroidism at different stages of zebrafishDanio rerio(Teleostei; Cyprinidae) skeleton development
Authors: Borisov Vasily , Shkil Fedor 
Published: June 2024

AbstractThyroid hormones (THs) are one of the main regulators of remodeling, homeostasis and development of skeletal tissues in teleosts, and the effects of hypo- and hyperthyroidism on skeleton are among the objectives of research in the fields of fishes development and evolution. However, in most experimental models used, the altered THs status is a constant characteristic of the developing organism, and the observed phenotypic outcomes are the cumulative consequences of multiple THs induced developmental changes. The effects of the transient fluctuations of THs content on the skeleton development have been studied much less. Here, we present experimental data on the developmental effects and phenotypic consequences of transient, pharmacologically induced thyrotoxicosis and hypothyroidism at different stages of zebrafish ossified skeleton patterning. In accordance with the results, skeleton structures differ in the timing and degree of THs sensitivity. Some of them displayed a notable shift in the developmental timing and rate, whereas other demonstrated a subtle or absence of reaction in respond to changes of THs content. The developmental stages also differ in THs sensitivity. A relatively short developmental period has been revealed, during which changes in THs level (mainly thyrotoxicosis) sharply increase the developmental instability and plasticity, leading to phenotypic consequences comparable to those in fish with permanently altered THs status. These findings allow us consider this period as a critical developmental window.Summary statementStudy of the developmental effects and phenotypic consequences of acute transient changes in thyroid hormones content have identified a critical developmental window for zebrafish’s skeletonEthics statementAll procedures with fish were carried out according to the guidelines and following the laws and ethics of the Russian Federation, and approved by the ethics committee of the Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences (Approval ID: N 95 issued on 27.05.2024).
ProEnd: A Comprehensive Database for Identifying HbYX Motif-Containing Proteins Across the Tree of Life
Authors: Salcedo-Tacuma David , Howells Giovanni , Mchose Coleman , Gutierrez-Diaz Aimer , Schupp Jane , Smith David M. 
Published: June 2024

AbstractThe proteasome plays a crucial role in cellular homeostasis by degrading misfolded, damaged, or unnecessary proteins. Understanding the regulatory mechanisms of proteasome activity is vital, particularly the interaction with activators containing the hydrophobic-tyrosine-any amino acid (HbYX) motif. Here, we present ProEnd, a comprehensive database designed to identify and catalog HbYX motif-containing proteins across the tree of life. Using a simple bioinformatics pipeline, we analyzed approximately 73 million proteins from 22,000 reference proteomes in the UniProt/SwissProt database. Our findings reveal the widespread presence of HbYX motifs in diverse organisms, highlighting their evolutionary conservation and functional significance. Notably, we observed an interesting prevalence of these motifs in viral proteomes, suggesting strategic interactions with the host proteasome. As validation two novel HbYX proteins found in this database were tested and found to directly interact with the proteasome. ProEnd’s extensive dataset and user-friendly interface enable researchers to explore the potential proteasomal regulator landscape, generating new hypotheses to advance proteasome biology. This resource is set to facilitate the discovery of novel therapeutic targets, enhancing our approach to treating diseases such as neurodegenerative disorders and cancer. Link:http://proend.org/
Syntaxin-2 coordinates endolysosomal trafficking to balance phagocytic uptake and phagolysosomal clearance in macrophages
Authors: Samanta Suman , Nandi Abhrajyoti , Datta Rupak , Dolai Subhankar 
Published: June 2024

SUMMARYPhagocytosis engulfs receptor-bound particles by structuring phagocytic cups that expand to form phagosome vesicles. Phagosomes fuse with endosomes and lysosomes to gradually mature into acidic, hydrolase-enriched phagolysosomes for content degradation. While an essential cellular process for eliminating unwanted substances to secure host defense and organismal homeostasis, defective or uncontrolled phagocytosis can be detrimental. Here, we report syntaxin-2 (Stx2), a poorly characterized SNARE in phagocytes, defines the course of macrophage phagocytosis by coordinating cell surface receptor density, phagocytic cup expansion, and phagosome maturation. Stx2 is expressed on the plasma membrane, phagosomes, early endosomes, and to some extent on recycling endosomes, late endosomes and VAMP4-positive compartments. Stx2 knockdown (Stx2-KD) augments engagement and uptake of IgG-opsonized particles by enhanced surface expression of Fc receptors (FcR) and efficient expansion of phagocytic cups. These events are driven by increased recycling of FcR, and enhanced delivery of early endosomes and VAMP4-positive post-Golgi compartments to phagocytic cups. Interestingly, Stx2-KD macrophages exhibit reduced secretion of pro-cathepsins with concomitant increase in lysosome content. However, Stx2 depletion prevents phagosome coalescence with late endosomes and lysosomes to impair maturation by depleted acquisition of cathepsins and reduced acidification. Consequently, macrophages depleted of Stx2 manifest uncontrolled uptake of IgG-opsonizedEscherichia coliand impaired digestion resulting in increased bacterial load. Collectively, we uncovered a previously unknown role of Stx2 as a critical balancer of phagocytic uptake and phagolysosomal clearance in macrophages, suggesting that it could be an attractive target for modulation of phagocytosis plasticity and to control aberrant phagocytosis.
Cell type-specific roles of FOXP1 in the excitatory neuronal lineage during early neocortical murine development
Authors: Ortiz Ana , Ayhan Fatma , Khandelwal Nitin , Outland Elliot , Jankovic Miranda , Harper Matthew , Konopka Genevieve 
Published: June 2024

SummaryFOXP1, a transcription factor enriched in the neocortex, is associated with autism spectrum disorders (ASD) and FOXP1 syndrome.Emx1Cre/+;Foxp1fl/flconditional deletion (Foxp1cKO) in the mouse cortex leads to overall reduced cortex thickness, alterations in cortical lamination, and changes in the relative thickness of cortical layers. However, the developmental and cell type-specific mechanisms underlying these changes remained unclear. We find thatFoxp1deletion results in accelerated pseudo-age during early neurogenesis, increased cell cycle exit during late neurogenesis, altered gene expression and chromatin accessibility, and selective migration deficits in a subset of upper-layer neurons. These data explain the postnatal differences observed in cortical layers and relative cortical thickness. We also highlight genes regulated by FOXP1 and their enrichment with high-confidence ASD or synaptic genes. Together, these results underscore a network of neurodevelopmental disorder-related genes that may serve as potential modulatory targets for postnatal modification relevant to ASD and FOXP1 syndrome.
Genetic and cellular basis of impaired phagocytosis and photoreceptor degeneration in CLN3 disease
Authors: Han Jimin , Chear Sueanne , Talbot Jana , Swier Vicki , Booth Clarissa , Reuben-Thomas Cheyenne , Dalvi Sonal , Weimer Jill M. , Hewitt Alex W. , Cook Anthony L. , Singh Ruchira 
Published: June 2024

AbstractPurposeCLN3 Batten disease (also known as Juvenile Neuronal Ceroid Lipofuscinosis; JNCL) is a lysosomal storage disorder that typically initiates with retinal degeneration but is followed by seizure onset, motor decline and premature death. Patient-derived CLN3 disease iPSC-RPE cells show defective phagocytosis of photoreceptor outer segments (POSs). Because modifier genes are implicated in CLN3 disease, our goal here was to investigate a direct link betweenCLN3mutation and POS phagocytosis defect.MethodsIsogenic control andCLN3mutant stem cell lines were generated by CRISPR-Cas9­mediated biallelic deletion of exons 7 and 8. A transgenicCLN3Δ7-8/Δ7-8(CLN3) Yucatan miniswine was also used to study the impact ofCLN3Δ7-8/Δ7-8mutation on POS phagocytosis. POS phagocytosis by cultured RPE cells was analyzed by Western blotting and immunohistochemistry. Electroretinogram, optical coherence tomography and histological analysis ofCLN3Δ7/8and wild-type miniswine eyes were carried out at 6-, 36-, or 48-month age.ResultsCLN3Δ7-8/Δ7-8RPE (CLN3RPE) displayed reduced POS binding and consequently decreased uptake of POS compared to isogenic control RPE cells. Furthermore, wild-type miniswine RPE cells phagocytosedCLN3Δ7-8/Δ7-8POS less efficiently than wild-type POS. Consistent with decreased POS phagocytosis, lipofuscin/autofluorescence was decreased inCLN3miniswine RPE at 36 months-of-age and was followed by almost complete loss of photoreceptors at 48 months of age.ConclusionsCLN3Δ7-8/Δ7-8mutation (that affects up to 85% patients) affects both RPE and POSs and leads to photoreceptor cell loss in CLN3 disease. Furthermore, both primary RPE dysfunction and mutant POS independently contribute to impaired POS phagocytosis in CLN3 disease.
Three-dimensional chromatin mapping of sensory neurons reveals that cohesin-dependent genomic domains are required for axonal regeneration
Authors: Palmisano Ilaria , Liu Tong , Gao Wei , Zhou Luming , Merkenschlager Matthias , Müller Franziska , Chadwick Jessica , Rivolta Rebecca Toscano , Kong Guiping , King James WD , Al-jibury Ediem , Yan Yuyang , Carlino Alessandro , Collison Bryce , De Vitis Eleonora , Gongala Sree , De Virgiliis Francesco , Wang Zheng , Giovanni Simone Di 
Published: June 2024

ABSTRACTThe in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression programme at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C and RNA-seq. We find that cohesin is required for the full induction of the regenerative transcriptional program, by organising 3D genomic domains required for the activation of regenerative genes. Importantly, loss of cohesin results in disruption of chromatin architecture at regenerative genes and severely impaired nerve regeneration. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent chromatin interactions in neuronal regeneration.
Liver-like glycogen metabolism supports glycolysis in naked mole-rat heart during ischaemia
Authors: Bundgaard Amanda , Wang Nini , Vyshkvorkina Iuliia , Jacome Burbano Maria Sol , Cherevatenko Maksym , Georgomanolis Theodoros , Dethloff Frederik , Giavalisco Patrick , Lackmann Jan-Wilm , Lewin Gary R , Frezza Christian , Reznick Jane 
Published: June 2024

AbstractAs a subterranean eusocial mammal, the naked mole-rat faces a particularly challenging environment characterised by patchily available food, low O2and high CO2levels. In response, naked mole-rats have evolved a suite of molecular and physiological adaptations to survive extreme hypoxia. Yet, how naked mole-rats rewire their metabolism to protect the heart has not been comprehensively addressed. Here, we performed comparative analyses of naked mole-rat and mouse organs exposed to ischaemic conditions. We show that naked mole-rats have retained features of foetal cardiac metabolism replacing fatty acid utilisation for a unique type of carbohydrate metabolism largely dependent on glycogen. We found that naked mole-rats have co-opted specialised liver-like glycogen handling mechanisms in the heart. Amongst these is the expression of liver-specific enzyme isoforms and amylase, a digestive enzyme known for starch breakdown in saliva and intestine but whose biological role in glycogen processing has not been fully recognised. We show that amylase is rapidly activated in ischaemia and hydrolyses internal glycosidic bonds for more efficient downstream processing. This biochemical adaptation occurred in both mouse and naked mole-rat livers but exclusively in the naked mole-rat heart, which retained higher ATP levels by maintaining an increased glycolytic flux in an amylase-dependent mechanism. Overall, we discovered a previously unknown type of glycogen metabolism in the naked mole-rat that holds relevance to pathologies where glycogen plays a role. Furthermore, we describe a novel type of metabolic plasticity in the heart which may be harnessed for cardiac disease.
Natural variation in protein kinase D modifies alcohol sensitivity inCaenorhabditis elegans
Authors: Clites Benjamin L. , Frohock Brooke , Koury Emily J. , Andersen Erik C. , Pierce Jonathan T. 
Published: June 2024

AbstractDifferences in naïve alcohol sensitivity between individuals are a strong predictor of later life alcohol use disorders (AUD). However, the genetic bases for alcohol sensitivity (beyond ethanol metabolism) and pharmacological approaches to modulate alcohol sensitivity remain poorly understood. We used a high-throughput behavioral screen to measure acute behavioral sensitivity to alcohol, a model of intoxication, in a genetically diverse set of over 150 wild strains of the nematodeCaenorhabditis elegans. We performed a genome-wide association study to identify loci that underlie natural variation in alcohol sensitivity. We identified five quantitative trait loci (QTL) and further show that variants in theC. elegansortholog of protein kinase D,dkf-2, likely underlie the chromosome V QTL. We found that resistance to intoxication was conferred bydkf-2loss-of-function mutations as well as partly by a PKD inhibitor in adkf-2-dependent manner. Protein kinase D might represent a conserved, druggable target to modify alcohol sensitivity with application towards AUD.Significance statementHere, we identify a novel role for protein kinase D (dkf-2) inC. elegansalcohol sensitivity. PKD, like protein kinase C, might represent a newly discovered druggable target to modify alcohol response. Identifying causal variants in genes of the remaining loci will likewise provide new insights into the genetic basis of variation in naïve alcohol sensitivity inC. elegansand other organisms.
Fe3O4nanoparticles shell amplify charge-extraction efficiency inDunaliellaphotovoltaics
Authors: Chen Hao-Hong , Wu Jing-xuan , Jiang Jian-Guo 
Published: June 2024

AbstractMicrobial biophotovoltaics (BPVs) harness photosynthetic microorganisms to convert light energy into electricity, making them highly attractive for renewable energy production. However, current BPVs typically exhibit low power densities, primarily due to inefficient electron transfer processes and the need for close contact and high interfacial area. Here, we propose a novel method of enhancingDunaliella-based BPVs using Fe3O4nanoparticle coatings. The Fe3O4-coatedDunaliellacells (DS@Fe3O4) establish intimate contact with the cellular electron transfer machinery and maximize the interfacial area, significantly improving electron transfer efficiency and reducing internal resistance. This approach achieved higher power outputs compared to nativeDunaliellaBPVs, with an optimal Fe3O4concentration of 2 mg/mL yielding the best performance. In contrast, SiO2coatings on Fe3O4(Fe3O4@SiO2) reduced electron transfer efficiency. These findings demonstrate that Fe3O4nanoparticle coatings provide a superior method for enhancing bio-electrochemical systems, advancing the application of BPVs for sustainable energy solutions and environmental applications.
The RAE1-STOP1 Module Reduces Sensitivity to Exogenous ABA Treatment by Regulating ABI5 in Arabidopsis
Authors: Zhang Yuqing , Huang Min , Liu Yinyin , Yang Mengmeng , Hou Yuqi , Huang Chao-Feng , Wang Ningning , Li Lei 
Published: June 2024

AbstractThe SENSITIVE TO PROTON RHIZOTOXICITY 1 (STOP1) transcription factor plays a pivotal role in maintaining cellular ion balance and governing aluminum tolerance in plants. Abscisic acid (ABA) participates in aluminum tolerance by inducing the expression of several genes that are STOP1 targets. However, the mechanisms underlying ABA signaling and STOP1-mediated gene expression remain poorly understood. The F-box protein RAE1, an SCF-type E3 ligase component, recognizes STOP1 and controls its ubiquitination and degradation. This study revealed that exogenous ABA supplementation reduced STOP1 levels by promoting the expression ofRAE1. Notably, bothRAE1loss-of-function mutants andSTOP1overexpressing lines showed enhanced sensitivity to exogenous ABA treatment, which correlated with early stage post-transcriptional upregulation of ABSCISIC ACID INSENSITIVE5 (ABI5). Our observations strongly suggest that RAE1 operates as an ABA-responsive factor, exerting control over STOP1 homeostasis, and thus establishing a negative feedback loop that controls ABA responses in Arabidopsis. Thus, our study revealed a novel function of the RAE1-STOP1 module in ABA signaling, highlighting its role in reducing ABA sensitivity by preventing ABI5 increase.Single Sentence SummaryF-box protein RAE1 functions as an exogenous ABA responsive mediator to reduce STOP1-mediated ABA sensitivity.
Experienced meditators show greater forward travelling cortical alpha wave strengths
Authors: Bailey Neil W , Hill Aron T , Godfrey Kate , Perera M. Prabhavi N. , Hohwy Jakob , Corcoran Andrew W. , Rogasch Nigel C. , Fitzgibbon Bernadette M. , Fitzgerald Paul B 
Published: June 2024

AbstractMindfulness meditation involves training attention, commonly towards the current sensory experience, with an attitude of non-judgemental awareness. Theoretical perspectives suggest meditation alters the brain’s predictive processing mechanisms, increasing the synaptic gain and precision with which sensory information is processed, and reducing the generation or elaboration of higher-order beliefs. Recent research suggests that forwards and backwards travelling cortical alpha waves provide an indication of these predictive processing functions. Here, we used electroencephalography (EEG) to test whether the strength of forwards and backwards travelling cortical alpha waves differed between experienced meditators and a matched sample of non-meditators, both during an eyes-closed resting state (N = 97) and during a visual cognitive (Go/No-go) task (N = 126). Our results showed that meditators produced stronger forwards travelling cortical alpha waves compared to non-meditators, both while resting with their eyes closed and during task performance. Meditators also exhibited weaker backwards travelling cortical alpha wave strength while resting with their eyes closed. These results may be indicative of a neural mechanism underpinning enhanced attention associated with meditation practice, as well as a potential neural marker of the reductions in resting mind-wandering that are suggested to be associated with meditation practice. The results also support models of brain function that suggest attention modification can be achieved by mental training aimed at increased processing of sensory information, which might be indexed by greater strength of forwards travelling cortical alpha waves.
Resistance to Spindle Inhibitors in Glioblastoma Depends on STAT3 and Therapy Induced Senescence
Authors: Zarco Natanael , Dovas Athanassios , de Araujo Farias Virginea , Nagaiah Naveen KH , Haddock Ashley , Sims Peter A. , Hambardzumyan Dolores , Meyer Christian T. , Canoll Peter , Rosenfeld Steven S. , Kenchappa Rajappa S. 
Published: June 2024

SUMMARYWhile mitotic spindle inhibitors specifically kill proliferating tumor cells without the toxicities of microtubule poisons, resistance has limited their clinical utility. Treating glioblastomas with the spindle inhibitors ispinesib, alisertib, or volasertib creates a subpopulation of therapy induced senescent cells that resist these drugs by relying upon the anti-apoptotic and metabolic effects of activated STAT3. Furthermore, these senescent cells expand the repertoire of cells resistant to these drugs by secreting an array of factors, including TGFβ, which induce proliferating cells to exit mitosis and become quiescent—a state that also resists spindle inhibitors. Targeting STAT3 restores sensitivity to each of these drugs by depleting the senescent subpopulation and inducing quiescent cells to enter the mitotic cycle. These results support a therapeutic strategy of targeting STAT3-dependent therapy-induced senescence to enhance the efficacy of spindle inhibitors for the treatment of glioblastoma.Highlights• Resistance to non-microtubule spindle inhibitors limits their efficacy in glioblastoma and depends on STAT3.• Resistance goes hand in hand with development of therapy induced senescence (TIS).• Spindle inhibitor resistant glioblastomas consist of three cell subpopulations—proliferative, quiescent, and TIS—with proliferative cells sensitive and quiescent and TIS cells resistant.• TIS cells secrete TGFβ, which induces proliferative cells to become quiescent, thereby expanding the population of resistant cells in a spindle inhibitor resistant glioblastoma• Treatment with a STAT3 inhibitor kills TIS cells and restores sensitivity to spindle inhibitors.
Hypoxia-Sonic Hedgehog Axis as a Driver of Primitive Hematopoiesis Development and Evolution in Cavefish
Authors: van der Weele Corine M. , Hospes Katrina C. , Rowe Katherine E. , Jeffery William R. 
Published: June 2024

AbstractThe teleostAstyanax mexicanusconsists of surface dwelling (surface fish) and cave dwelling (cavefish) forms. Cavefish have evolved in subterranean habitats characterized by reduced oxygen levels (hypoxia) and show constructive and regressive phenotypic traits controlled by increased Sonic hedgehog (Shh) signaling along the embryonic midline. The enhancement of primitive hematopoietic domains, which are formed bilaterally in the anterior and posterior lateral plate mesoderm, are responsible for the development of more larval erythrocytes in cavefish relative to surface fish. In this study, we determine the role of hypoxia and Shh signaling in the development and evolution of primitive hematopoiesis in cavefish. We show that hypoxia treatment during embryogenesis increases primitive hematopoiesis and erythrocyte development in surface fish. We also demonstrate that upregulation of Shh midline signaling by treatment with the Smoothened agonist SAG increases primitive hematopoiesis and erythrocyte development in surface fish, whereas Shh downregulation via treatment with the Smoothened inhibitor cyclopamine decreases these traits in cavefish. Together these results suggest that hematopoietic enhancement is regulated by hypoxia and the Shh signaling system. Lastly, we demonstrate that hypoxia treatment enhances expression of Shh signaling along the midline of surface fish embryos. Thus, we conclude that a hypoxia-Shh axis may drive the adaptive evolution of primitive hematopoiesis and erythrocyte development in cavefish.HighlightsHypoxia increases hematopoiesis and erythrocytes in surface fishShh upregulation increases hematopoiesis and erythrocytes in surface fishShh inhibition decreases hematopoiesis and erythrocytes in cavefishHypoxia upregulates Shh along the embryonic midline in surface fish