bluuebunny/crossref_metadata_2025_split huggingface dataset:
AMPA receptors modulate enhanced dopamine neuronal activity induced by the combined administration of venlafaxine and brexpiprazole
Authors: Daniels Stephen , El Mansari Mostafa , Blier Pierre 
Published: August 2024

AbstractAddition of dopamine (DA)/serotonin (5-HT) partial agonists to 5-HT/norepinephrine (NE) reuptake inhibitors are commonly used to enhance the antidepressant response. The simultaneous inhibition of 5-HT and NE transporters with venlafaxine and its combination of brexpiprazole, which blocks the α2-adrenergic autoreceptor on NE terminals, could constitute a superior strategy. Anesthetized rats received venlafaxine and brexpiprazole for 2 and 14 days, then the firing activity of dorsal raphe nucleus 5-HT, locus coeruleus NE, and ventral tegmental area DA neurons were assessed. Net 5-HT and NE neurotransmissions were evaluated by assessing the tonic activation of 5-HT1A, and α1- and α2-adrenergic receptors in the hippocampus. The combination of brexpiprazole with venlafaxine resulted in normalized 5-HT and NE neuron activity, which occurred earlier than that with venlafaxine alone. A significant enhancement of the tonic activation of 5-HT1A receptors and α2-adrenoceptors in the hippocampus was observed following administration of the combination for 14 days. The combination more than doubled the number of DA neurons per electrode descent, after both 2 and 14 days, while this increase was observed only after 14 days of venlafaxine administration. This increase in population activity was prevented by NBQX, an AMPA receptor antagonist. In conclusion, early during administration, the combination of venlafaxine with brexpiprazole normalized firing activity of 5-HT and NE neurons, and increased the population activity of DA neurons through AMPA receptors. In the hippocampus, there was an overall increase in both 5-HT and NE transmissions. These results imply that this strategy could be a rapid-acting approach to treat depression.
Adapting cytoskeleton-mitochondria patterning with myocyte differentiation by promyogenic PRR33
Authors: Fu Xuyang , Zhang Feng , Dong Xiaoxuan , Pu Linbin , Feng Yan , Xu Yang , Gao Feng , Liang Tian , Kang Jianmeng , Sun Hongke , Hong Tingting , Liu Yunxia , Zhou Hongmei , Jiang Jun , Yin Deling , Hu Xinyang , Wang Da-Zhi , Ding Jian , Chen Jinghai 
Published: August 2024

Abstract
Coordinated cytoskeleton-mitochondria organization during myogenesis is crucial for muscle development and function. Our understanding of the underlying regulatory mechanisms remains inadequate. Here, we identified a novel muscle-enriched protein, PRR33, which is upregulated during myogenesis and acts as a promyogenic factor. Depletion of Prr33 in C2C12 represses myoblast differentiation. Genetic deletion of Prr33 in mice reduces myofiber size and decreases muscle strength. The Prr33 mutant mice also exhibit impaired myogenesis and defects in muscle regeneration in response to injury. Interactome and transcriptome analyses reveal that PRR33 regulates cytoskeleton and mitochondrial function. Remarkably, PRR33 interacts with DESMIN, a key regulator of cytoskeleton-mitochondria organization in muscle cells. Abrogation of PRR33 in myocytes substantially abolishes the interaction of DESMIN filaments with mitochondria, leading to abnormal intracellular accumulation of DESMIN and mitochondrial disorganization/dysfunction in myofibers. Together, our findings demonstrate that PRR33 and DESMIN constitute an important regulatory module coordinating mitochondrial organization with muscle differentiation.
Astrocytes and the tumor microenvironment inflammatory state dictate the killing of glioblastoma cells by Smac mimetic compounds
Authors: Malone Kyle , Dugas Melanie , Earl Nathalie , Alain Tommy , LaCasse Eric C. , Beug Shawn T. 
Published: August 2024

AbstractSmac mimetic compounds (SMCs) are small molecule drugs that sensitize cancer cells to TNF-α-induced cell death and have multiple immunostimulatory effects through alterations in NF-κB signaling. The combination of SMCs with immunotherapies has been reported to result in durable cures of up to 40% in syngeneic, orthotopic murine glioblastoma (GBM) models. Herein, we find that SMC resistance is not due to a cell-intrinsic mechanism of resistance. We thus evaluated the contribution of GBM and brain stromal components to identify parameters leading to SMC efficacy and resistance. The common physiological features of GBM tumors, such as hypoxia, hyaluronic acid, and glucose deprivation were found not to play a significant role in SMC efficacy. SMCs induced the death of microglia and macrophages, which are the major immune infiltrates in the tumor microenvironment. This death of microglia and macrophages then enhances the ability of SMCs to induce GBM cell death. Conversely, astrocytes promoted GBM cell growth and abrogated the ability of SMCs to induce death of GBM cells. The astrocyte-mediated resistance can be overcome in the presence of exogenous TNF-α. Overall, our results highlight that SMCs can induce death of microglia and macrophages, which then provides a source of death ligands for GBM cells, and that the targeting of astrocytes is a potential mechanism for overcoming SMC resistance for the treatment of GBM.
GPR50 regulates neuronal development as a mitophagy receptor
Authors: Liu Ji-Chuan , Zhao Xiu-Yun , Wu Ming-Lei , Shi Yi-fan , Huang Ze-Ping , Fang Li-Pao , Zhu Chao , Peng Xuan , Shi Zi-Ling , Lan Li-Jun , Ji Wen-Li , Luo Li , Feng Lei , Zhang Zeng-Li , Xu De-en , Li Shao , Qin Zheng-Hong , Sun Yan-Yun , Schachner Melitta , Ma Quan-Hong 
Published: August 2024

AbstractNeurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.
Toll-like receptor 4 deficiency in Purkinje neurons drives cerebellar ataxia by impairing the BK channel-mediated after-hyperpolarization and cytosolic calcium homeostasis
Authors: Zhu Jianwei , Qiu Wenqiao , Wei Fan , Zhang Jin , Yuan Ying , Liu Ling , Cheng Meixiong , Xiong Huan , Xu Ruxiang 
Published: August 2024

AbstractToll-like receptor (TLR) 4 contributes to be the induction of neuroinflammation by recognizing pathology-associated ligands and activating microglia. In addition, numerous physiological signaling factors act as agonists or antagonists of TLR4 expressed by non-immune cells. Recently, TLR4 was found to be highly expressed in cerebellar Purkinje neurons (PNs) and involved in the maintenance of motor coordination through non-immune pathways, but the precise mechanisms remain unclear. Here we report that mice with PN specific TLR4 deletion (TLR4PKO mice) exhibited motor impairments consistent with cerebellar ataxia, reduced PN dendritic arborization and spine density, fewer parallel fiber (PF) – PN and climbing fiber (CF) – PN synapses, reduced BK channel expression, and impaired BK-mediated after-hyperpolarization, collectively leading to abnormal PN firing. Moreover, the impaired PN firing in TLR4PKO mice could be rescued with BK channel opener. The PNs of TLR4PKO mice also exhibited abnormal mitochondrial structure, disrupted mitochondrial endoplasmic reticulum tethering, and reduced cytosolic calcium, changes that may underly abnormal PN firing and ultimately drive ataxia. These results identify a previously unknown role for TLR4 in regulating PN firing and maintaining cerebellar function.
Intraocular pressure, primary open-angle glaucoma and the risk of retinal vein occlusion: A Mendelian randomization mediation analysis
Authors: Katsimpris Andreas , Baumeister Sebastian-Edgar , Voulgari Nafsika , Baurecht Hansjörg , Kandarakis Stylianos , Nolde Michael 
Published: August 2024

Abstract
Background
The etiological connection between intraocular pressure (IOP) and the risk of retinal vein occlusion (RVO) remains elusive, particularly regarding whether this risk emanates from the direct influence of elevated intraocular pressure (IOP), irrespective of the presence of primary open-angle glaucoma (POAG), or if it arises as a consequence of the sequelae of POAG. Therefore, we conducted a Mendelian Randomization (MR) mediation analysis to elucidate the mediating role of POAG in the association between IOP and RVO.

Methods
We identified 47 single-nucleotide polymorphisms (SNPs) associated with IOP (P-value < 5 × 10−8) leveraging data from a genome-wide association study (GWAS) (N = 97,653) obtained from the UK Biobank and 50 SNPs associated with POAG (P-value < 5 × 10−8) from a GWAS meta-analysis (16,677 cases and 199,580 controls). We related these SNPs with RVO using a GWAS of 775 RVO cases and 376,502 controls from FinnGen. By utilizing univariable and multivariable MR analyses we calculated the total effect of IOP on RVO and estimated the degree to which POAG mediates this association.

Results
MR analyses showed that higher IOP is associated with higher RVO risk (odds ratio of RVO per 1 mmHg increase in IOP: 1.53; 95% confidence interval: 1.04 to 2.26; p-value = 0.03). Moreover, our MR mediation analysis suggested that 91.6% of the total effect of IOP on RVO risk was mediated through POAG. The primary results were consistent with estimates of pleiotropy-robust MR methods.

Conclusion
Our findings suggest that higher IOP increases the risk of RVO and that the majority of this effect is mediated through POAG.
An anionic two dimensional covalent organic framework from tetratopic borate centres pillared by lithium ions
Authors: Asgari Darosch , Grüneberg Julia , Luo Yunkai , Küçükkeçeci Hüseyin , Ghosh Samrat , Chevelkov Veniamin , Fischer-Lang Sabrina , Roeser Jérôme , Lange Adam , Dunn Bruce , Gradzielski Michael , Thomas Arne 
Published: August 2024

AbstractNon-covalent interactions play an important role for the framework formation of two-dimensional covalent organic frameworks. Until now, π–π interactions and hydrogen bonding are the main reported forces facilitating the stacking of framework layers. Here, we present a two-dimensional anionic covalent organic framework based on tetratopic borate linkages, where layers are connected by ionic interactions between the linkage site and counter cations. The crystalline covalent organic framework is accessed through the formation of an amorphous borate-based polymer and subsequent solvothermal treatment. The progress of crystallization is investigated, revealing the crystallite growth and morphological change from agglomerated dense particles to hollow crystallite spheres. Due to the pillared nature, the crystallites can be exfoliated into nanosheets by sonication of the material in the presence of methanol. The crystallization and ordered arrangement of the lithium ions in the interlayer space is shown to benefit the conductivity tenfold compared to the amorphous material.
Environmental permittivity-asymmetric BIC metasurfaces with electrical reconfigurability
Authors: Hu Haiyang , Lu Wenzheng , Antonov Alexander , Berté Rodrigo , Maier Stefan A. , Tittl Andreas 
Published: August 2024

AbstractAchieving precise spectral and temporal light manipulation at the nanoscale remains a critical challenge in nanophotonics. While photonic bound states in the continuum (BICs) have emerged as a powerful means of controlling light, their reliance on geometrical symmetry breaking for obtaining tailored resonances makes them highly susceptible to fabrication imperfections, and their generally fixed asymmetry factor fundamentally limits applications in reconfigurable metasurfaces. Here, we introduce the concept of environmental symmetry breaking by embedding identical resonators into a surrounding medium with carefully placed regions of contrasting refractive indexes, activating permittivity-driven quasi-BIC resonances (ε-qBICs) without altering the underlying resonator geometry and unlocking an additional degree of freedom for light manipulation through active tuning of the surrounding dielectric environment. We demonstrate this concept by integrating polyaniline (PANI), an electro-optically active polymer, to achieve electrically reconfigurable ε-qBICs. This integration not only demonstrates rapid switching speeds and exceptional durability but also boosts the system’s optical response to environmental perturbations. Our strategy significantly expands the capabilities of resonant light manipulation through permittivity modulation, opening avenues for on-chip optical devices, advanced sensing, and beyond.
Loss-of-function variants in ITSN1 confer high risk of Parkinson’s disease
Authors: Skuladottir Astros Th. , Tragante Vinicius , Sveinbjornsson Gardar , Helgason Hannes , Sturluson Arni , Bjornsdottir Anna , Jonsson Palmi , Palmadottir Vala , Sveinsson Olafur A. , Jensson Brynjar O. , Gudjonsson Sigurjon A. , Ivarsdottir Erna V. , Gisladottir Rosa S. , Gunnarsson Arni F. , Walters G. Bragi , Jonsdottir Gudrun A. , Thorgeirsson Thorgeir E. , Bjornsdottir Gyda , Holm Hilma , Gudbjartsson Daniel F. , Sulem Patrick , Stefansson Hreinn , Stefansson Kari 
Published: August 2024

AbstractParkinson’s disease (PD) is a debilitating neurodegenerative disorder and its rising global incidence highlights the need for the identification of modifiable risk factors. In a gene-based burden test of rare variants (8647 PD cases and 777,693 controls) we discovered a novel association between loss-of-function variants in ITSN1 and PD. This association was further supported with burden data from the Neurodegenerative Disease Knowledge Portal and the Accelerating Medicines Partnership Parkinson’s Disease Knowledge Platform. Our findings show that Rho GTPases and disruptions in synaptic vesicle transport may be involved in the pathogenesis of PD, pointing to the possibility of novel therapeutic approaches.
Structure of a fully assembled γδ T cell antigen receptor
Authors: Gully Benjamin S. , Ferreira Fernandes João , Gunasinghe Sachith D. , Vuong Mai T. , Lui Yuan , Rice Michael T. , Rashleigh Liam , Lay Chan-sien , Littler Dene R. , Sharma Sumana , Santos Ana Mafalda , Venugopal Hariprasad , Rossjohn Jamie , Davis Simon J. 
Published: August 2024

AbstractT cells in jawed vertebrates comprise two lineages, αβ T cells and γδ T cells, defined by the antigen receptors they express—that is, αβ and γδ T cell receptors (TCRs), respectively. The two lineages have different immunological roles, requiring that γδ TCRs recognize more structurally diverse ligands1. Nevertheless, the receptors use shared CD3 subunits to initiate signalling. Whereas the structural organization of αβ TCRs is understood2,3, the architecture of γδ TCRs is unknown. Here, we used cryogenic electron microscopy to determine the structure of a fully assembled, MR1-reactive, human Vγ8Vδ3 TCR–CD3δγε2ζ2 complex bound by anti-CD3ε antibody Fab fragments4,5. The arrangement of CD3 subunits in γδ and αβ TCRs is conserved and, although the transmembrane α-helices of the TCR-γδ and -αβ subunits differ markedly in sequence, packing of the eight transmembrane-helix bundles is similar. However, in contrast to the apparently rigid αβ TCR2,3,6, the γδ TCR exhibits considerable conformational heterogeneity owing to the ligand-binding TCR-γδ subunits being tethered to the CD3 subunits by their transmembrane regions only. Reducing this conformational heterogeneity by transfer of the Vγ8Vδ3 TCR variable domains to an αβ TCR enhanced receptor signalling, suggesting that γδ TCR organization reflects a compromise between efficient signalling and the ability to engage structurally diverse ligands. Our findings reveal the marked structural plasticity of the TCR on evolutionary timescales, and recast it as a highly versatile receptor capable of initiating signalling as either a rigid or flexible structure.
Infrared spectral library of tooth enamel from African ungulates for accurate electron spin resonance dating
Authors: Toffolo Michael B. , Richard Maïlys 
Published: August 2024

AbstractElectron spin resonance coupled with uranium-series dating (ESR/U-series) of carbonate hydroxyapatite in tooth enamel is the main technique used to obtain age determinations from Pleistocene fossils beyond the range of radiocarbon dating. This chronological information allows to better understand diachronic change in the palaeontological record, especially with regard to the evolution of the genus Homo. Given the relative paucity of human teeth at palaeontological and archaeological localities, ESR/U-series is widely applied to the teeth of ungulate species. However, the accuracy of ESR/U-series ages is greatly affected by the incorporation of uranium in the enamel during burial in sediments. It has been shown that uranium content is positively correlated with an increased degree of atomic order in carbonate hydroxyapatite crystals, the latter determined using infrared spectroscopy. Here we present a reference infrared spectral library of tooth enamel from African ungulates, based on the grinding curve method, which serves as baseline to track the diagenetic history of carbonate hydroxyapatite in different species and thus select the best-preserved specimens for dating.
The synergistic effect of Ficus carica nanoparticles and Praziquantel on mice infected by Schistosoma mansoni cercariae
Authors: El-Attar Naira A. , El-Sawi Mamdouh R. , El-Shabasy Eman A. 
Published: August 2024

AbstractBilharzia is a parasitic flatworm that causes schistosomiasis, a neglected tropical illness worldwide. Praziquantel (PZQ) is a commercial single treatment of schistosomiasis so alternative drugs are needed to get rid of its side effects on the liver. The current study aimed to estimate the effective role of Ficus carica nanoparticles (Fc-NPCs), silver nanoparticles (Ag-NPCs) and Ficus carica nanoparticles loaded on silver nanoparticles (Fc-Ag NPCs) on C57BL/6 black female mice infected by Schistosoma mansoni and treated with PZQ treatment. It was proved that schistosomiasis causes liver damage in addition to the PZQ is ineffective as an anti-schistosomiasis; it is recorded in the infected mice group and PZQ treated group as in liver function tests, oxidative stress markers & anti-oxidants, pro-inflammatory markers, pro-apoptotic and anti-apoptotic markers also in liver cells’ DNA damage. The amelioration in all tested parameters has been clarified in nanoparticle-protected mice groups. The Fc-Ag NPCs + PZQ group recorded the best preemptive effects as anti-schistosomiasis. Fc-NPCs, Ag-NPCs and Fc-Ag NPCs could antagonize PZQ effects that were observed in amelioration of all tested parameters. The study showed the phytochemicals’ nanoparticles groups have an ameliorated effect on the health of infected mice.
Differential patch-leaving behavior during probabilistic foraging in humans and gerbils
Authors: Güldener Lasse , Saravanakumar Parthiban , Happel Max F. K. , Ohl Frank W. , Vollmer Maike , Pollmann Stefan 
Published: August 2024

AbstractForaging confronts animals, including humans, with the need to balance exploration and exploitation: exploiting a resource until it depletes and then deciding when to move to a new location for more resources. Research across various species has identified rules for when to leave a depleting patch, influenced by environmental factors like patch quality. Here we compare human and gerbil patch-leaving behavior through two analogous tasks: a visual search for humans and a physical foraging task for gerbils, both involving patches with randomly varying initial rewards that decreased exponentially. Patch-leaving decisions of humans but not gerbils follow an incremental mechanism based on reward encounters that is considered optimal for maximizing reward yields in variable foraging environments. The two species also differ in their giving-up times, and some human subjects tend to overharvest. However, gerbils and individual humans who do not overharvest are equally sensitive to declining collection rates in accordance with the marginal value theorem. Altogether this study introduces a paradigm for a between-species comparison on how to resolve the exploitation-exploration dilemma.
Improving wheat grain composition for human health by constructing a QTL atlas for essential minerals
Authors: Sigalas Petros P. , Shewry Peter R. , Riche Andrew , Wingen Luzie , Feng Cong , Siluveru Ajay , Chayut Noam , Burridge Amanda , Uauy Cristobal , Castle March , Parmar Saroj , Philp Charlie , Steele David , Orford Simon , Leverington-Waite Michelle , Cheng Shifeng , Griffiths Simon , Hawkesford Malcolm J. 
Published: August 2024

AbstractWheat is an important source of minerals for human nutrition and increasing grain mineral content can contribute to reducing mineral deficiencies. Here, we identify QTLs for mineral micronutrients in grain of wheat by determining the contents of six minerals in a total of eleven sample sets of three biparental populations from crosses between A.E. Watkins landraces and cv. Paragon. Twenty-three of the QTLs are mapped in two or more sample sets, with LOD scores above five in at least one set with the increasing alleles for sixteen of the QTLs being present in the landraces and seven in Paragon. Of these QTLs, the number for each mineral varies between three and five and they are located on 14 of the 21 chromosomes, with clusters on chromosomes 5A (four), 6A (three), and 7A (three). The gene content within 5 megabases of DNA on either side of the marker for the QTL with the highest LOD score is determined and the gene responsible for the strongest QTL (chromosome 5A for Ca) identified as an ATPase transporter gene (TraesCS5A02G543300) using mutagenesis. The identification of these QTLs, together with associated SNP markers and candidate genes, will facilitate the improvement of grain nutritional quality.