bluuebunny/crossref_metadata_2025_split huggingface dataset:
Islands in a sea of sand: The role of Tarim Basin polities in global trade during late antiquity
Authors: Høisæter Tomas Larsen 
Published: October 2023

AbstractMuch of the literature on the Ancient Silk Road has examined its operation through the prism of empires and East-West connections. Yet in the last few decades several scholars have sought to re-examine this framework, with a number suggesting that the roots of the Silk Road exchange network should be sought instead in the many polities which lay along its routes. This article similarly seeks to challenge the traditional ‘Silk Road of Empires’ concept by applying approaches from global history and examining both archaeological and written sources from the third- and fourth-century kingdom of Kroraina in the south-eastern Tarim Basin in Xinjiang, Western China. The first goal of this article is to consider Kroraina’s inclusion in the wider Silk Roads network and how this network influenced local elite consumption. The second is to examine Kroraina’s role in the Silk Road network. It is argued that polities like Kroraina played a crucial role in facilitating and maintaining trans-Eurasian trade in Late Antiquity.
Postcolonial Pessimisms and Alternative Spatial Practices: Critical Interpretation of the concept of the Third Space through the Case of Fatahillah Square, Indonesia
Authors: Park Junyoung 
Published: October 2023

AbstractSpatial practice is at the core of postcolonial geography's response to the geography of colonialism. However, the methodology of postcolonial spatial practice is linked to pessimisms within the postcolonial debate. This study aims to overcome pessimisms of postcolonialism by analysing a case of postcolonial spatial practice through literature review, expert interview, and field study. The case under investigation is Fatahillah Square in Jakarta, which has been transformed through postcolonial spatial practices from a space that symbolised the tragedy of colonialism into one of culture and art. Here, the characteristics of Homi K. Bhabha's “third space” are apparent, but this case may also be interpreted as an extension of the concept. Through the hybrid and emancipatory plurality of its spatial practice, it refutes the pessimisms of postcolonialism and calls for further postcolonial practice and analysis.
PI3K/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer
Authors: Deng Huan , Chen Yamei , Wang Li , Zhang Yibi , Hang Qingqing , Li Peijing , Zhang Peng , Ji Jing , Song Hai , Chen Ming , Jin Ying 
Published: October 2023

AbstractOur previous study revealed that PI3K/AKT/mTOR signaling was associated with SCLC radioresistance. SBC2 cells were used as primary radioresistance models, while H446 cells were continuously exposed to ionizing radiation (IR) to develop acquired radioresistance. Cell viability and apoptosis assays were used to investigate synergistic effects of BEZ235/GSK2126458 and IR in vitro, while immunoblotting, metabolite quantitative analysis and bioinformatic analyses were utilized to explore the underlying mechanism. Both genetically engineered mouse models (GEMM) and subcutaneous tumor models were used to confirm the synergistic effect in vivo. Key molecules of PI3K/AKT/mTOR signaling were upregulated after IR, which was correlated with primary radioresistance, and they were more expressed in acquired radioresistant cells. BEZ235/GSK2126458 effectively enhanced the cytotoxic effects of IR. BEZ235/GSK2126458 plus IR elevated γ-H2AX and p-Nrf2 expression, suggesting DNA and oxidative stress damage were intensified. Mechanistically, BEZ235/GSK2126458 plus IR significantly reduced the expression of G6PD protein, the rate-limiting enzyme of the pentose phosphate pathway (PPP). In detail, PI3K/mTOR inhibitors reinforced interaction between G6PD and HSPA8/HSC70, and G6PD was degraded by chaperone-mediated autophagy processes. Their metabolites (NADPH and R-5P) were decreased, and ROS levels were indirectly elevated, both of which exacerbated cell death. PI3K/AKT/mTOR signaling activator, insulin, enhanced SCLC radioresistance, while the synergistic effect of BEZ235/GSK2126458 and IR can be attenuated by N-acetylcysteine, and enhanced by 6-amino niacinamide. GEMM and allograft transplantation assays further confirmed their synergistic effect in vivo. This study provided insights into the connection between PI3K/AKT/mTOR signaling and the PPP underlying radioresistance and provided evidence of mechanisms supporting PI3K/mTOR inhibitors as possible therapeutic strategies to abrogate SCLC radioresistance.
Targeting c-Jun inhibits fatty acid oxidation to overcome tamoxifen resistance in estrogen receptor-positive breast cancer
Authors: Jiang Cen , Zhu Youzhi , Chen Huaying , Lin Junyu , Xie Ruiwang , Li Weiwei , Xue Jiajie , Chen Ling , Chen Xiangjin , Xu Sunwang 
Published: October 2023

AbstractTamoxifen-based endocrine therapy remains a major adjuvant therapy for estrogen receptor (ER)-positive breast cancer (BC). However, many patients develop tamoxifen resistance, which results in recurrence and poor prognosis. Herein, we show that fatty acid oxidation (FAO) was activated in tamoxifen-resistant (TamR) ER-positive BC cells by performing bioinformatic and functional studies. We also reveal that CPT1A, the rate-limiting enzyme of FAO, was significantly overexpressed and that its enzymatic activity was enhanced in TamR cells. Mechanistically, the transcription factor c-Jun was activated by JNK kinase-mediated phosphorylation. Activated c-Jun bound to the TRE motif in the CPT1A promoter to drive CPT1A transcription and recruited CBP/P300 to chromatin, catalysing histone H3K27 acetylation to increase chromatin accessibility, which ensured more effective transcription of CPT1A and an increase in the FAO rate, eliminating the cytotoxic effects of tamoxifen in ER-positive BC cells. Pharmacologically, inhibiting CPT1A enzymatic activity with the CPT1 inhibitor etomoxir or blocking c-Jun phosphorylation with a JNK inhibitor restored the tamoxifen sensitivity of TamR cells. Clinically, high levels of phosphorylated c-Jun and CPT1A were observed in ER-positive BC tissues in patients with recurrence after tamoxifen therapy and were associated with poor survival. These results indicate that the assessment and targeting of the JNK/c-Jun-CPT1A-FAO axis will provide promising insights for clinical management, increased tamoxifen responses and improved outcomes for ER-positive BC patients.
Concurrently mapping quantitative trait loci associations from multiple subspecies within hybrid populations
Authors: Warburton Christie L. , Costilla Roy , Engle Bailey N. , Moore Stephen S. , Corbet Nicholas J. , Fordyce Geoffry , McGowan Michael R. , Burns Brian M. , Hayes Ben J. 
Published: October 2023

AbstractMany of the world’s agriculturally important plant and animal populations consist of hybrids of subspecies. Cattle in tropical and sub-tropical regions for example, originate from two subspecies, Bos taurus indicus (Bos indicus) and Bos taurus taurus (Bos taurus). Methods to derive the underlying genetic architecture for these two subspecies are essential to develop accurate genomic predictions in these hybrid populations. We propose a novel method to achieve this. First, we use haplotypes to assign SNP alleles to ancestral subspecies of origin in a multi-breed and multi-subspecies population. Then we use a BayesR framework to allow SNP alleles originating from the different subspecies differing effects. Applying this method in a composite population of B. indicus and B. taurus hybrids, our results show that there are underlying genomic differences between the two subspecies, and these effects are not identified in multi-breed genomic evaluations that do not account for subspecies of origin effects. The method slightly improved the accuracy of genomic prediction. More significantly, by allocating SNP alleles to ancestral subspecies of origin, we were able to identify four SNP with high posterior probabilities of inclusion that have not been previously associated with cattle fertility and were close to genes associated with fertility in other species. These results show that haplotypes can be used to trace subspecies of origin through the genome of this hybrid population and, in conjunction with our novel Bayesian analysis, subspecies SNP allele allocation can be used to increase the accuracy of QTL association mapping in genetically diverse populations.
Taphonomic experiments reveal authentic molecular signals for fossil melanins and verify preservation of phaeomelanin in fossils
Authors: Slater Tiffany S. , Ito Shosuke , Wakamatsu Kazumasa , Zhang Fucheng , Sjövall Peter , Jarenmark Martin , Lindgren Johan , McNamara Maria E. 
Published: October 2023

AbstractMelanin pigments play a critical role in physiological processes and shaping animal behaviour. Fossil melanin is a unique resource for understanding the functional evolution of melanin but the impact of fossilisation on molecular signatures for eumelanin and, especially, phaeomelanin is not fully understood. Here we present a model for the chemical taphonomy of fossil eumelanin and phaeomelanin based on thermal maturation experiments using feathers from extant birds. Our results reveal which molecular signatures are authentic signals for thermally matured eumelanin and phaeomelanin, which signatures are artefacts derived from the maturation of non-melanin molecules, and how these chemical data are impacted by sample preparation. Our model correctly predicts the molecular composition of eumelanins in diverse vertebrate fossils from the Miocene and Cretaceous and, critically, identifies direct molecular evidence for phaeomelanin in these fossils. This taphonomic framework adds to the geochemical toolbox that underpins reconstructions of melanin evolution and of melanin-based coloration in fossil vertebrates.
Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment
Authors: Vinikoor Tra , Dzidotor Godwin K. , Le Thinh T. , Liu Yang , Kan Ho-Man , Barui Srimanta , Chorsi Meysam T. , Curry Eli J. , Reinhardt Emily , Wang Hanzhang , Singh Parbeen , Merriman Marc A. , D’Orio Ethan , Park Jinyoung , Xiao Shuyang , Chapman James H. , Lin Feng , Truong Cao-Sang , Prasadh Somasundaram , Chuba Lisa , Killoh Shaelyn , Lee Seok-Woo , Wu Qian , Chidambaram Ramaswamy M. , Lo Kevin W. H. , Laurencin Cato T. , Nguyen Thanh D. 
Published: October 2023

AbstractOsteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we present an injectable, biodegradable piezoelectric hydrogel, made of short electrospun poly-L-lactic acid nanofibers embedded inside a collagen matrix, which can be injected into the joints and self-produce localized electrical cues under ultrasound activation to drive cartilage healing. In vitro, data shows that the piezoelectric hydrogel with ultrasound can enhance cell migration and induce stem cells to secrete TGF-β1, which promotes chondrogenesis. In vivo, the rabbits with osteochondral critical-size defects receiving the ultrasound-activated piezoelectric hydrogel show increased subchondral bone formation, improved hyaline-cartilage structure, and good mechanical properties, close to healthy native cartilage. This piezoelectric hydrogel is not only useful for cartilage healing but also potentially applicable to other tissue regeneration, offering a significant impact on the field of regenerative tissue engineering.
Hyper-cores promote localization and efficient seeding in higher-order processes
Authors: Mancastroppa Marco , Iacopini Iacopo , Petri Giovanni , Barrat Alain 
Published: October 2023

AbstractGoing beyond networks, to include higher-order interactions of arbitrary sizes, is a major step to better describe complex systems. In the resulting hypergraph representation, tools to identify structures and central nodes are scarce. We consider the decomposition of a hypergraph in hyper-cores, subsets of nodes connected by at least a certain number of hyperedges of at least a certain size. We show that this provides a fingerprint for data described by hypergraphs and suggests a novel notion of centrality, the hypercoreness. We assess the role of hyper-cores and nodes with large hypercoreness in higher-order dynamical processes: such nodes have large spreading power and spreading processes are localized in central hyper-cores. Additionally, in the emergence of social conventions very few committed individuals with high hypercoreness can rapidly overturn a majority convention. Our work opens multiple research avenues, from comparing empirical data to model validation and study of temporally varying hypergraphs.
Mucosal application of the broadly neutralizing antibody 10-1074 protects macaques from cell-associated SHIV vaginal exposure
Authors: Suphaphiphat Karunasinee , Desjardins Delphine , Lorin Valérie , Dimant Nastasia , Bouchemal Kawthar , Bossevot Laetitia , Galpin-Lebreau Maxence , Dereuddre-Bosquet Nathalie , Mouquet Hugo , Le Grand Roger , Cavarelli Mariangela 
Published: October 2023

AbstractPassive immunization using broadly neutralizing antibodies (bNAbs) is investigated in clinical settings to inhibit HIV-1 acquisition due to the lack of a preventive vaccine. However, bNAbs efficacy against highly infectious cell-associated virus transmission has been overlooked. HIV-1 transmission mediated by infected cells present in body fluids likely dominates infection and aids the virus in evading antibody-based immunity. Here, we show that the anti-N-glycans/V3 loop HIV-1 bNAb 10-1074 formulated for topical vaginal application in a microbicide gel provides significant protection against repeated cell-associated SHIV162P3 vaginal challenge in non-human primates. The treated group has a significantly lower infection rate than the control group, with 5 out of 6 animals fully protected from the acquisition of infection. The findings suggest that mucosal delivery of potent bnAbs may be a promising approach for preventing transmission mediated by infected cells and support the use of anti-HIV-antibody-based strategies as potential microbicides in human clinical trials.
In-situ electro-responsive through-space coupling enabling foldamers as volatile memory elements
Authors: Li Jinshi , Shen Pingchuan , Zhuang Zeyan , Wu Junqi , Tang Ben Zhong , Zhao Zujin 
Published: October 2023

AbstractVoltage-gated processing units are fundamental components for non-von Neumann architectures like memristor and electric synapses, on which nanoscale molecular electronics have possessed great potentials. Here, tailored foldamers with furan‒benzene stacking (f-Fu) and thiophene‒benzene stacking (f-Th) are designed to decipher electro-responsive through-space interaction, which achieve volatile memory behaviors via quantum interference switching in single-molecule junctions. f-Fu exhibits volatile turn-on feature while f-Th performs stochastic turn-off feature with low voltages as 0.2 V. The weakened orbital through-space mixing induced by electro-polarization dominates stacking malposition and quantum interference switching. f-Fu possesses higher switching probability and faster responsive time, while f-Th suffers incomplete switching and longer responsive time. High switching ratios of up to 91 for f-Fu is realized by electrochemical gating. These findings provide evidence and interpretation of the electro-responsiveness of non-covalent interaction at single-molecule level and offer design strategies of molecular non-von Neumann architectures like true random number generator.
The pan-genome and local adaptation of Arabidopsis thaliana
Authors: Kang Minghui , Wu Haolin , Liu Huanhuan , Liu Wenyu , Zhu Mingjia , Han Yu , Liu Wei , Chen Chunlin , Song Yan , Tan Luna , Yin Kangqun , Zhao Yusen , Yan Zhen , Lou Shangling , Zan Yanjun , Liu Jianquan 
Published: October 2023

AbstractArabidopsis thaliana serves as a model species for investigating various aspects of plant biology. However, the contribution of genomic structural variations (SVs) and their associate genes to the local adaptation of this widely distribute species remains unclear. Here, we de novo assemble chromosome-level genomes of 32 A. thaliana ecotypes and determine that variable genes expand the gene pool in different ecotypes and thus assist local adaptation. We develop a graph-based pan-genome and identify 61,332 SVs that overlap with 18,883 genes, some of which are highly involved in ecological adaptation of this species. For instance, we observe a specific 332 bp insertion in the promoter region of the HPCA1 gene in the Tibet-0 ecotype that enhances gene expression, thereby promotes adaptation to alpine environments. These findings augment our understanding of the molecular mechanisms underlying the local adaptation of A. thaliana across diverse habitats.
The endoribonuclease Arlr is required to maintain lipid homeostasis by downregulating lipolytic genes during aging
Authors: Sun Xiaowei , Shen Jie , Perrimon Norbert , Kong Xue , Wang Dan 
Published: October 2023

AbstractWhile disorders in lipid metabolism have been associated with aging and age-related diseases, how lipid metabolism is regulated during aging is poorly understood. Here, we characterize the Drosophila endoribonuclease CG2145, an ortholog of mammalian EndoU that we named Age-related lipid regulator (Arlr), as a regulator of lipid homeostasis during aging. In adult adipose tissues, Arlr is necessary for maintenance of lipid storage in lipid droplets (LDs) as flies age, a phenotype that can be rescued by either high-fat or high-glucose diet. Interestingly, RNA-seq of arlr mutant adipose tissues and RIP-seq suggest that Arlr affects lipid metabolism through the degradation of the mRNAs of lipolysis genes – a model further supported by the observation that knockdown of Lsd-1, regucalcin, yip2 or CG5162, which encode genes involved in lipolysis, rescue the LD defects of arlr mutants. In addition, we characterize DendoU as a functional paralog of Arlr and show that human ENDOU can rescue arlr mutants. Altogether, our study reveals a role of ENDOU-like endonucleases as negative regulator of lipolysis.
Intracellular bacteria in cancer—prospects and debates
Authors: Schorr Lena , Mathies Marius , Elinav Eran , Puschhof Jens 
Published: October 2023

AbstractRecent evidence suggests that some human cancers may harbor low-biomass microbial ecosystems, spanning bacteria, viruses, and fungi. Bacteria, the most-studied kingdom in this context, are suggested by these studies to localize within cancer cells, immune cells and other tumor microenvironment cell types, where they are postulated to impact multiple cancer-related functions. Herein, we provide an overview of intratumoral bacteria, while focusing on intracellular bacteria, their suggested molecular activities, communication networks, host invasion and evasion strategies, and long-term colonization capacity. We highlight how the integration of sequencing-based and spatial techniques may enable the recognition of bacterial tumor niches. We discuss pitfalls, debates and challenges in decisively proving the existence and function of intratumoral microbes, while reaching a mechanistic elucidation of their impacts on tumor behavior and treatment responses. Together, a causative understanding of possible roles played by intracellular bacteria in cancer may enable their future utilization in diagnosis, patient stratification, and treatment.
The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate
Authors: Weisshaar Nina , Ma Sicong , Ming Yanan , Madi Alaa , Mieg Alessa , Hering Marvin , Zettl Ferdinand , Mohr Kerstin , Ten Bosch Nora , Stichling Diana , Buettner Michael , Poschet Gernot , Klinke Glynis , Schulz Michael , Kunze-Rohrbach Nina , Kerber Carolin , Klein Isabel Madeleine , Wu Jingxia , Wang Xi , Cui Guoliang 
Published: October 2023

AbstractThe malate shuttle is traditionally understood to maintain NAD+/NADH balance between the cytosol and mitochondria. Whether the malate shuttle has additional functions is unclear. Here we show that chronic viral infections induce CD8+ T cell expression of GOT1, a central enzyme in the malate shuttle. Got1 deficiency decreased the NAD+/NADH ratio and limited antiviral CD8+ T cell responses to chronic infection; however, increasing the NAD+/NADH ratio did not restore T cell responses. Got1 deficiency reduced the production of the ammonia scavenger 2-ketoglutarate (2-KG) from glutaminolysis and led to a toxic accumulation of ammonia in CD8+ T cells. Supplementation with 2-KG assimilated and detoxified ammonia in Got1-deficient T cells and restored antiviral responses. These data indicate that the major function of the malate shuttle in CD8+ T cells is not to maintain the NAD+/NADH balance but rather to detoxify ammonia and enable sustainable ammonia-neutral glutamine catabolism in CD8+ T cells during chronic infection.
Subretinal timrepigene emparvovec in adult men with choroideremia: a randomized phase 3 trial
Authors: MacLaren Robert E. , Fischer M. Dominik , Gow James A. , Lam Byron L. , Sankila Eeva-Marja K. , Girach Aniz , Panda Sushil , Yoon Dan , Zhao Guolin , Pennesi Mark E. 
Published: October 2023

AbstractChoroideremia is a rare, X-linked retinal degeneration resulting in progressive vision loss. A randomized, masked, phase 3 clinical trial evaluated the safety and efficacy over 12 months of follow-up in adult males with choroideremia randomized to receive a high-dose (1.0 × 1011 vector genomes (vg); n = 69) or low-dose (1.0 × 1010 vg; n = 34) subretinal injection of the AAV2-vector-based gene therapy timrepigene emparvovec versus non-treated control (n = 66). Most treatment-emergent adverse events were mild or moderate. The trial did not meet its primary endpoint of best-corrected visual acuity (BCVA) improvement. In the primary endpoint analysis, three of 65 participants (5%) in the high-dose group, one of 34 (3%) participants in the low-dose group and zero of 62 (0%) participants in the control group had ≥15-letter Early Treatment Diabetic Retinopathy Study (ETDRS) improvement from baseline BCVA at 12 months (high dose, P = 0.245 versus control; low dose, P = 0.354 versus control). As the primary endpoint was not met, key secondary endpoints were not tested for significance. In a key secondary endpoint, nine of 65 (14%), six of 35 (18%) and one of 62 (2%) participants in the high-dose, low-dose and control groups, respectively, experienced ≥10-letter ETDRS improvement from baseline BCVA at 12 months. Potential opportunities to enhance future gene therapy studies for choroideremia include optimization of entry criteria (more preserved retinal area), surgical techniques and clinical endpoints. EudraCT registration: 2015-003958-41.