bluuebunny/crossref_metadata_2025_split huggingface dataset:
UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance
Authors: Huang Yumei , Yang Xijie , Lu Yanwei , Zhao Ye , Meng Rui , Zhang Sheng , Dong Xiaorong , Xu Shuangbing , Wu Gang 
Published: September 2020

AbstractUBE2O, an E2/E3 hybrid ubiquitin-protein ligase, has been implicated in the regulation of adipogenesis, erythroid differentiation, and tumor proliferation. However, its role in cancer radioresistance remains completely unknown. Here, we uncover that UBE2O interacts and targets Mxi1 for ubiquitination and degradation at the K46 residue. Furthermore, we show that genetical or pharmacological blockade of UBE2O impairs tumor progression and radioresistance in lung cancer in vitro and in vivo, and these effects can be restored by Mxi1 inhibition. Moreover, we demonstrate that UBE2O is overexpressed and negatively correlated with Mxi1 protein levels in lung cancer tissues. Collectively, our work reveals that UBE2O facilitates tumorigenesis and radioresistance by promoting Mxi1 ubiquitination and degradation, suggesting that UBE2O is an attractive radiosensitization target for the treatment of lung cancer.
M2 macrophage-induced lncRNA PCAT6 facilitates tumorigenesis and angiogenesis of triple-negative breast cancer through modulation of VEGFR2
Authors: Dong Fang , Ruan Shengnan , Wang Jinlong , Xia Yun , Le Kehao , Xiao Xiaoyun , Hu Ting , Wang Qiong 
Published: September 2020

AbstractAs a common female malignancy, triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancers (BC). This study further studied the role of long noncoding RNA (lncRNA) prostate cancer-associated transcript 6 (PCAT6) in TNBC. Functional assays, including EdU, wound healing, transwell, and immunofluorescence staining, revealed the effect of PCAT6 on cell proliferation, migration, and EMT process. The tube-formation assay disclosed the function of PCAT6 on angiogenesis. In vivo assays were also established to explore the impact of PCAT6 on tumor growth and microangiogenesis. The results revealed that PCAT6 boosted TNBC cell proliferation, migration, and angiogenesis both in vitro and in vivo. Then, this study unveiled that M2 macrophage secreted VEGF to stimulate the upregulation of PCAT6, thus promoting angiogenesis in TNBC. Next, through bioinformatics analysis and mechanism assays, we identified that PCAT6 positively regulated VEGFR2 expression via ceRNA pattern and then participated in VEGFR/AKT/mTOR signaling pathway to accelerate angiogenesis. Moreover, PCAT6 bound USP14, a deubiquitinase, to induce the deubiquitination of VEGFR2. On the whole, M2 macrophage-induced upregulation of PCAT6 facilitates TNBC tumorigenesis through modulation of VEGFR2 expression via ceRNA and deubiquitination patterns.
KAP1-associated transcriptional inhibitory complex regulates C2C12 myoblasts differentiation and mitochondrial biogenesis via miR-133a repression
Authors: Zhang Jialing , Hua Chaoju , Zhang Yu , Wei Peng , Tu Yaping , Wei Taotao 
Published: September 2020

AbstractThe differentiation of myoblasts plays a key role in the growth of biological individuals and the reconstruction of muscle tissue. Several microRNAs are significantly upregulated during the differentiation of myoblasts and their target genes have been explored. However, the molecular mechanisms underlying the transcriptional regulation of microRNAs remain elusive. In the present study, we found that the expression of miR-133a is increased during the differentiation of C2C12 myoblasts. miR-133a mimic is sufficient to induce the biogenesis of mitochondria and differentiation of C2C12 myoblasts whereas miR-133a inhibitor abolishes cell differentiation. Using CRISPR affinity purification in situ of regulatory elements (CAPTURE) technique, we further dissected the regulatory mechanisms of miR-133a expression and found that KAP1-associated transcription complex accounts for the suppression of miR-133a in C2C12 myoblasts. Knockdown of KAP1 increased the expression of miR-133a, which contributed to the biogenesis of mitochondria and differentiation of C2C12 myoblasts. To our knowledge, this is the first study using the CAPTURE technology to identify the regulatory factors of miR-133a during cell differentiation, which may provide new ideas for understanding the precision regulatory machinery of microRNAs during different biological processes.
Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model
Authors: Pradhan Priyadarshika , Majhi Olivia , Biswas Abhijit , Joshi Vinod Kumar , Sinha Devanjan 
Published: September 2020

AbstractParkinson’s disease (PD) is a neuromotor disorder, primarily manifested by motor anomalies due to progressive loss of dopaminergic neurons. Although alterations in genetic factors have been linked with its etiology, exponential accumulation of environmental entities such as reactive oxygen species (ROS) initiate a cyclic chain reaction resulting in accumulation of cellular inclusions, dysfunctional mitochondria, and overwhelming of antioxidant machinery, thus accelerating disease pathogenesis. Involvement of oxidative stress in PD is further substantiated through ROS induced Parkinsonian models and elevated oxidative markers in clinical PD samples; thereby, making modulation of neuronal oxidative load as one of the major approaches in management of PD. Here we have found a potent antioxidant moiety Scopoletin (Sp), a common derivative in most of the nootropic herbs, with robust neuroprotective ability. Sp increased cellular resistance to ROS through efficient recycling of GSH to prevent oxidative damage. The Sp treated cells showed higher loads of reduced glutathione making them resistant to perturbation of antioxidant machinery or neurotoxin MPP+. Sp could restore the redox balance, mitochondrial function, and prevented oxidative damage, leading to recovery of dopaminergic neural networks and motion abilities in Drosophila genetic model of PD. Our data also suggest that Sp, in combination increases the therapeutic potency of L-DOPA by mitigating its chronic toxicity. Together, we highlight the possible ability of Sp in preventing oxidative stress mediated loss of dopaminergic neurons and at the same time enhance the efficacy of dopamine recharging regimens.
A miR-210-3p regulon that controls the Warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer
Authors: Du Ye , Wei Na , Ma Ruolin , Jiang Shuheng , Song Dong 
Published: September 2020

AbstractReprogrammed energy metabolism, especially the Warburg effect (aerobic glycolysis), is an emerging hallmark of cancer. Different from other breast cancer subtypes, triple-negative breast cancer (TNBC) exhibits high metabolic remodeling, increased aggressiveness and lack of targeted therapies. MicroRNAs (miRNA) are essential to TNBC malignant phenotypes. However, little is known about the contribution of miRNA to aerobic glycolysis in TNBC. Through an integrated analysis and functional verification, we reported that several miRNAs significantly correlates to the Warburg effect in TNBC, including miR-210-3p, miR-105-5p, and miR-767-5p. Ectopic expression of miR-210-3p enhanced glucose uptake, lactate production, extracellular acidification rate, colony formation ability, and reduced serum starvation-induced cell apoptosis. Moreover, GPD1L and CYGB were identified as two functional mediators of miR-210-3p in TNBC. Mechanistically, miR-210-3p targeted GPD1L to maintain HIF-1α stabilization and suppressed p53 activity via CYGB. Ultimately, miR-210-3p facilitated aerobic glycolysis through modulating the downstream glycolytic genes of HIF-1α and p53. Taken together, our results decipher miRNAs that regulate aerobic glycolysis and uncover that miR-210-3p specifically contributes to the Warburg effect in TNBC.
miR-378-3p maintains the size of mouse primordial follicle pool by regulating cell autophagy and apoptosis
Authors: Sun Xiaowen , Klinger Francesca Gioia , Liu Jing , De Felici Massimo , Shen Wei , Sun Xiaofeng 
Published: September 2020

AbstractPrimordial follicle pool provides all available oocytes throughout the whole reproductive life span. Abnormal regulation in primordial follicle assembly leads to abnormal size of primordial follicle pool, even causes infertility. Here, miR-378-3p was proved to regulate mouse primordial follicle assembly both in vivo and in vitro. The expression of miR-378-3p significantly increased in mice ovaries from 17.5 dpc (days post coitum) up to 3 dpp (day post partum) compared with the expression of 16.5 dpc ovaries, which suggested that miR-378-3p was involved in primordial follicle assembly. To uncover the underlying mechanism, newborn mice ovaries were cultured in vitro in the presence of rapamycin and 3-methyladenine, which showed that the expression of miR-378-3p changed together with the percentage of primordial follicle. Moreover, during the normal process of primordial follicle assembly between 17.6 dpc and 3 dpp, autophagy is activated, while, apoptosis is inhibited. The in vivo results showed that newborn mice starved for 1.5 days showing the increased miR-378-3p, activated autophagy and inhibited apoptosis in the ovaries, had more percentage of primordial follicles. Over-expression of miR-378-3p using miR-378-3p agomir caused increased percentage of primordial follicle, increased level of autophagy, and decreased level of apoptosis. Knockdown of miR-378-3p by miR-378-3p antiagomir had the opposite results. Using pmirGLO Dual-Luciferase miRNA Target Expression system, we confirmed both PDK1 and Caspase9 were targets of miR-378-3p, which suggested that miR-378-3p activated autophagy by targeting PDK1 and inhibited apoptosis by targeting Caspase9. MiR-378-3p could be used as a biomarker of diseases caused by abnormal size of primordial follicle pool for diagnosis, prevention, or therapy.
Forest carbon sink neutralized by pervasive growth-lifespan trade-offs
Authors: Brienen R. J. W. , Caldwell L. , Duchesne L. , Voelker S. , Barichivich J. , Baliva M. , Ceccantini G. , Di Filippo A. , Helama S. , Locosselli G. M. , Lopez L. , Piovesan G. , Schöngart J. , Villalba R. , Gloor E. 
Published: September 2020

AbstractLand vegetation is currently taking up large amounts of atmospheric CO2, possibly due to tree growth stimulation. Extant models predict that this growth stimulation will continue to cause a net carbon uptake this century. However, there are indications that increased growth rates may shorten trees′ lifespan and thus recent increases in forest carbon stocks may be transient due to lagged increases in mortality. Here we show that growth-lifespan trade-offs are indeed near universal, occurring across almost all species and climates. This trade-off is directly linked to faster growth reducing tree lifespan, and not due to covariance with climate or environment. Thus, current tree growth stimulation will, inevitably, result in a lagged increase in canopy tree mortality, as is indeed widely observed, and eventually neutralise carbon gains due to growth stimulation. Results from a strongly data-based forest simulator confirm these expectations. Extant Earth system model projections of global forest carbon sink persistence are likely too optimistic, increasing the need to curb greenhouse gas emissions.
Helicase LSH/Hells regulates kinetochore function, histone H3/Thr3 phosphorylation and centromere transcription during oocyte meiosis
Authors: Baumann Claudia , Ma Wei , Wang Xiaotian , Kandasamy Muthugapatti K. , Viveiros Maria M. , De La Fuente Rabindranath 
Published: September 2020

AbstractCentromeres are epigenetically determined nuclear domains strictly required for chromosome segregation and genome stability. However, the mechanisms regulating centromere and kinetochore chromatin modifications are not known. Here, we demonstrate that LSH is enriched at meiotic kinetochores and its targeted deletion induces centromere instability and abnormal chromosome segregation. Superresolution chromatin analysis resolves LSH at the inner centromere and kinetochores during oocyte meiosis. LSH knockout pachytene oocytes exhibit reduced HDAC2 and DNMT-1. Notably, mutant oocytes show a striking increase in histone H3 phosphorylation at threonine 3 (H3T3ph) and accumulation of major satellite transcripts in both prophase-I and metaphase-I chromosomes. Moreover, knockout oocytes exhibit centromere fusions, ectopic kinetochore formation and abnormal exchange of chromatin fibers between paired bivalents and asynapsed chromosomes. Our results indicate that loss of LSH affects the levels and chromosomal localization of H3T3ph and provide evidence that, by maintaining transcriptionally repressive heterochromatin, LSH may be essential to prevent deleterious meiotic recombination events at repetitive centromeric sequences.
Cropland expansion in the United States produces marginal yields at high costs to wildlife
Authors: Lark Tyler J. , Spawn Seth A. , Bougie Matthew , Gibbs Holly K. 
Published: September 2020

AbstractRecent expansion of croplands in the United States has caused widespread conversion of grasslands and other ecosystems with largely unknown consequences for agricultural production and the environment. Here we assess annual land use change 2008–16 and its impacts on crop yields and wildlife habitat. We find that croplands have expanded at a rate of over one million acres per year, and that 69.5% of new cropland areas produced yields below the national average, with a mean yield deficit of 6.5%. Observed conversion infringed upon high-quality habitat that, relative to unconverted land, had provided over three times higher milkweed stem densities in the Monarch butterfly Midwest summer breeding range and 37% more nesting opportunities per acre for waterfowl in the Prairie Pothole Region of the Northern Great Plains. Our findings demonstrate a pervasive pattern of encroachment into areas that are increasingly marginal for production, but highly significant for wildlife, and suggest that such tradeoffs may be further amplified by future cropland expansion.
Amalgamated cross-species transcriptomes reveal organ-specific propensity in gene expression evolution
Authors: Fukushima Kenji , Pollock David D. 
Published: September 2020

AbstractThe origins of multicellular physiology are tied to evolution of gene expression. Genes can shift expression as organisms evolve, but how ancestral expression influences altered descendant expression is not well understood. To examine this, we amalgamate 1,903 RNA-seq datasets from 182 research projects, including 6 organs in 21 vertebrate species. Quality control eliminates project-specific biases, and expression shifts are reconstructed using gene-family-wise phylogenetic Ornstein–Uhlenbeck models. Expression shifts following gene duplication result in more drastic changes in expression properties than shifts without gene duplication. The expression properties are tightly coupled with protein evolutionary rate, depending on whether and how gene duplication occurred. Fluxes in expression patterns among organs are nonrandom, forming modular connections that are reshaped by gene duplication. Thus, if expression shifts, ancestral expression in some organs induces a strong propensity for expression in particular organs in descendants. Regardless of whether the shifts are adaptive or not, this supports a major role for what might be termed preadaptive pathways of gene expression evolution.
Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis
Authors: Bolte Ashley C. , Dutta Arun B. , Hurt Mariah E. , Smirnov Igor , Kovacs Michael A. , McKee Celia A. , Ennerfelt Hannah E. , Shapiro Daniel , Nguyen Bao H. , Frost Elizabeth L. , Lammert Catherine R. , Kipnis Jonathan , Lukens John R. 
Published: September 2020

AbstractTraumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model of TBI that mild forms of brain trauma cause severe deficits in meningeal lymphatic drainage that begin within hours and last out to at least one month post-injury. To investigate a mechanism underlying impaired lymphatic function in TBI, we examined how increased intracranial pressure (ICP) influences the meningeal lymphatics. We demonstrate that increased ICP can contribute to meningeal lymphatic dysfunction. Moreover, we show that pre-existing lymphatic dysfunction before TBI leads to increased neuroinflammation and negative cognitive outcomes. Finally, we report that rejuvenation of meningeal lymphatic drainage function in aged mice can ameliorate TBI-induced gliosis. These findings provide insights into both the causes and consequences of meningeal lymphatic dysfunction in TBI and suggest that therapeutics targeting the meningeal lymphatic system may offer strategies to treat TBI.
Single-cell transcriptome maps of myeloid blood cell lineages in Drosophila
Authors: Cho Bumsik , Yoon Sang-Ho , Lee Daewon , Koranteng Ferdinand , Tattikota Sudhir Gopal , Cha Nuri , Shin Mingyu , Do Hobin , Hu Yanhui , Oh Sue Young , Lee Daehan , Vipin Menon A. , Moon Seok Jun , Perrimon Norbert , Nam Jin-Wu , Shim Jiwon 
Published: September 2020

AbstractThe Drosophila lymph gland, the larval hematopoietic organ comprised of prohemocytes and mature hemocytes, has been a valuable model for understanding mechanisms underlying hematopoiesis and immunity. Three types of mature hemocytes have been characterized in the lymph gland: plasmatocytes, lamellocytes, and crystal cells, which are analogous to vertebrate myeloid cells, yet molecular underpinnings of the lymph gland hemocytes have been less investigated. Here, we use single-cell RNA sequencing to comprehensively analyze heterogeneity of developing hemocytes in the lymph gland, and discover previously undescribed hemocyte types including adipohemocytes, stem-like prohemocytes, and intermediate prohemocytes. Additionally, we identify the developmental trajectory of hemocytes during normal development as well as the emergence of the lamellocyte lineage following active cellular immunity caused by wasp infestation. Finally, we establish similarities and differences between embryonically derived- and larval lymph gland hemocytes. Altogether, our study provides detailed insights into the hemocyte development and cellular immune responses at single-cell resolution.
Long-term autophagy is sustained by activation of CCTβ3 on lipid droplets
Authors: Ogasawara Yuta , Cheng Jinglei , Tatematsu Tsuyako , Uchida Misaki , Murase Omi , Yoshikawa Shogo , Ohsaki Yuki , Fujimoto Toyoshi 
Published: September 2020

AbstractMacroautophagy initiates by formation of isolation membranes, but the source of phospholipids for the membrane biogenesis remains elusive. Here, we show that autophagic membranes incorporate newly synthesized phosphatidylcholine, and that CTP:phosphocholine cytidylyltransferase β3 (CCTβ3), an isoform of the rate-limiting enzyme in the Kennedy pathway, plays an essential role. In starved mouse embryo fibroblasts, CCTβ3 is initially recruited to autophagic membranes, but upon prolonged starvation, it concentrates on lipid droplets that are generated from autophagic degradation products. Omegasomes and isolation membranes emanate from around those lipid droplets. Autophagy in prolonged starvation is suppressed by knockdown of CCTβ3 and is enhanced by its overexpression. This CCTβ3-dependent mechanism is also present in U2OS, an osteosarcoma cell line, and autophagy and cell survival in starvation are decreased by CCTβ3 depletion. The results demonstrate that phosphatidylcholine synthesis through CCTβ3 activation on lipid droplets is crucial for sustaining autophagy and long-term cell survival.
Segmented flow generator for serial crystallography at the European X-ray free electron laser
Authors: Echelmeier Austin , Cruz Villarreal Jorvani , Messerschmidt Marc , Kim Daihyun , Coe Jesse D. , Thifault Darren , Botha Sabine , Egatz-Gomez Ana , Gandhi Sahir , Brehm Gerrit , Conrad Chelsie E. , Hansen Debra T. , Madsen Caleb , Bajt Saša , Meza-Aguilar J. Domingo , Oberthür Dominik , Wiedorn Max O. , Fleckenstein Holger , Mendez Derek , Knoška Juraj , Martin-Garcia Jose M. , Hu Hao , Lisova Stella , Allahgholi Aschkan , Gevorkov Yaroslav , Ayyer Kartik , Aplin Steve , Ginn Helen Mary , Graafsma Heinz , Morgan Andrew J. , Greiffenberg Dominic , Klujev Alexander , Laurus Torsten , Poehlsen Jennifer , Trunk Ulrich , Mezza Davide , Schmidt Bernd , Kuhn Manuela , Fromme Raimund , Sztuk-Dambietz Jolanta , Raab Natascha , Hauf Steffen , Silenzi Alessandro , Michelat Thomas , Xu Chen , Danilevski Cyril , Parenti Andrea , Mekinda Leonce , Weinhausen Britta , Mills Grant , Vagovic Patrik , Kim Yoonhee , Kirkwood Henry , Bean Richard , Bielecki Johan , Stern Stephan , Giewekemeyer Klaus , Round Adam R. , Schulz Joachim , Dörner Katerina , Grant Thomas D. , Mariani Valerio , Barty Anton , Mancuso Adrian P. , Weierstall Uwe , Spence John C. H. , Chapman Henry N. , Zatsepin Nadia , Fromme Petra , Kirian Richard A. , Ros Alexandra 
Published: September 2020

AbstractSerial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) allows structure determination of membrane proteins and time-resolved crystallography. Common liquid sample delivery continuously jets the protein crystal suspension into the path of the XFEL, wasting a vast amount of sample due to the pulsed nature of all current XFEL sources. The European XFEL (EuXFEL) delivers femtosecond (fs) X-ray pulses in trains spaced 100 ms apart whereas pulses within trains are currently separated by 889 ns. Therefore, continuous sample delivery via fast jets wastes >99% of sample. Here, we introduce a microfluidic device delivering crystal laden droplets segmented with an immiscible oil reducing sample waste and demonstrate droplet injection at the EuXFEL compatible with high pressure liquid delivery of an SFX experiment. While achieving ~60% reduction in sample waste, we determine the structure of the enzyme 3-deoxy-D-manno-octulosonate-8-phosphate synthase from microcrystals delivered in droplets revealing distinct structural features not previously reported.
Identification of molecular quantum states using phase-sensitive forces
Authors: Najafian Kaveh , Meir Ziv , Sinhal Mudit , Willitsch Stefan 
Published: September 2020

AbstractQuantum-logic techniques used to manipulate quantum systems are now increasingly being applied to molecules. Previous experiments on single trapped diatomic species have enabled state detection with excellent fidelities and highly precise spectroscopic measurements. However, for complex molecules with a dense energy-level structure improved methods are necessary. Here, we demonstrate an enhanced quantum protocol for molecular state detection using state-dependent forces. Our approach is based on interfering a reference and a signal force applied to a single atomic and molecular ion. By changing the relative phase of the forces, we identify states embedded in a dense molecular energy-level structure and monitor state-to-state inelastic scattering processes. This method can also be used to exclude a large number of states in a single measurement when the initial state preparation is imperfect and information on the molecular properties is incomplete. While the present experiments focus on N$${}_{2}^{+}$$

2

+

, the method is general and is expected to be of particular benefit for polyatomic systems.