bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent Responses of Dominant Forest Tree Species to Manipulated Canopy and Understory N Additions in Terms of Foliage Stoichiometric, Photosynthetic, and Hydraulic Traits
Authors: Zhang Zhenzhen , Zhao Ping , Ouyang Lei , Zhao Xiuhua , Zhu Liwei , Ni Guangyan 
Published: September 2021

AbstractNitrogen (N) deposition effects on the stoichiometric balance and photosynthetic and hydraulic couplings in subtropical forests has drawn wide attentions. The previously adopted understory application of N fertilization is criticized because it might ignore foliar N retention for different species. This paper reports a fertilizing application from the canopy (CAN) and under the canopy (UAN) in a phosphorus (P) limited ecosystem. Foliage stoichiometric, photosynthetic, and hydraulic traits of six dominant species were measured and analyzed. Both treatments equally enhanced foliage N and N/P, but not foliage P, who was highly species‐specific depending on tree height, which implied enhanced P limitation. Decreased isotope abundance of 15N (δ15N) that approaching to the level in the urea fertilizer under CAN suggested the existence of canopy retention of N. Besides, N response sensitivity of N, P and δ15N that positively related to tree height (H) under CAN indicated different exposure to the added N, which promoted stoichiometric imbalance among species. The photosynthetic traits represented by net photosynthesis (An) increased under both treatments. A divergent foliar photosynthetic and hydraulic traits variation was identified by significant decreased stomatal conductance (gs) and An/gs for CAN treatments, which induced the elevated isotope abundance of 13C (δ13C). Correspondingly, foliage hydraulic traits that shifted to water use efficiency axis were identified only under CAN in principal component analysis. Overall, our results proved that the canopy absorption and species heterogeneity should be considered regarding foliar safety versus efficiency trade‐off in response to nitrogen additions in the future.
A human antibody against human endothelin receptor type A that exhibits antitumor potency
Authors: Ju Man-Seok , Ahn Hye-Mi , Han Seong-Gu , Ko Sanghwan , Na Jung-Hyun , Jo Migyeong , Lim Chung Su , Ko Byoung Joon , Yu Yeon Gyu , Lee Won-Kyu , Kim Youn-Jae , Jung Sang Taek 
Published: September 2021

AbstractEndothelin receptor A (ETA), a class A G-protein-coupled receptor (GPCR), is involved in the progression and metastasis of colorectal, breast, lung, ovarian, and prostate cancer. We overexpressed and purified human endothelin receptor type A in Escherichia coli and reconstituted it with lipid and membrane scaffold proteins to prepare an ETA nanodisc as a functional antigen with a structure similar to that of native GPCR. By screening a human naive immune single-chain variable fragment phage library constructed in-house, we successfully isolated a human anti-ETA antibody (AG8) exhibiting high specificity for ETA in the β-arrestin Tango assay and effective inhibitory activity against the ET-1-induced signaling cascade via ETA using either a CHO-K1 cell line stably expressing human ETA or HT-29 colorectal cancer cells, in which AG8 exhibited IC50 values of 56 and 51 nM, respectively. In addition, AG8 treatment repressed the transcription of inhibin βA and reduced the ETA-induced phosphorylation of protein kinase B and extracellular regulated kinase. Furthermore, tumor growth was effectively inhibited by AG8 in a colorectal cancer mouse xenograft model. The human anti-ETA antibody isolated in this study could be used as a potential therapeutic for cancers, including colorectal cancer.
Unraveling the physiological roles of retinoic acid receptor-related orphan receptor α
Authors: Lee Ji Min , Kim Hyunkyung , Baek Sung Hee 
Published: September 2021

AbstractRetinoic acid receptor-related orphan receptor-α (RORα) is a member of the orphan nuclear receptor family and functions as a transcriptional activator in response to circadian changes. Circadian rhythms are complex cellular mechanisms regulating diverse metabolic, inflammatory, and tumorigenic gene expression pathways that govern cyclic cellular physiology. Disruption of circadian regulators, including RORα, plays a critical role in tumorigenesis and facilitates the development of inflammatory hallmarks. Although RORα contributes to overall fitness among anticancer, anti-inflammatory, lipid homeostasis, and circadian clock mechanisms, the molecular mechanisms underlying the mode of transcriptional regulation by RORα remain unclear. Nonetheless, RORα has important implications for pharmacological prevention of cancer, inflammation, and metabolic diseases, and understanding context-dependent RORα regulation will provide an innovative approach for unraveling the functional link between cancer metabolism and rhythm changes.
Gut microbiota involved in leptospiral infections
Authors: Xie Xufeng , Liu Jiuxi , Chen Xi , Zhang Shilei , Tang Ruibo , Wu Xiaoyu , Zhang Wenlong , Cao Yongguo 
Published: September 2021

Abstract
Leptospirosis is a re-emerging zoonotic disease worldwide. Intestinal bleeding is a common but neglected symptom in severe leptospirosis. The regulatory mechanism of the gut microbiota on leptospirosis is still unclear. In this study, we found that Leptospira interrogans infection changed the composition of the gut microbiota in mice. Weight loss and an increased leptospiral load in organs were observed in the gut microbiota-depleted mice compared with those in the control mice. Moreover, fecal microbiota transplantation (FMT) to the microbiota-depleted mice reversed these effects. The phagocytosis response and inflammatory response in bone marrow-derived macrophages and thioglycolate-induced peritoneal macrophages were diminished in the microbiota-depleted mice after infection. However, the phagocytosis response and inflammatory response in resident peritoneal macrophage were not affected in the microbiota-depleted mice after infection. The diminished macrophage disappearance reaction (bacterial entry into the peritoneum acutely induced macrophage adherence to form local clots and out of the fluid phase) led to an increased leptospiral load in the peritoneal cavity in the microbiota-depleted mice. In addition, the impaired capacity of macrophages to clear leptospires increased leptospiral dissemination in Leptospira-infected microbiota-depleted mice. Our study identified the microbiota as an endogenous defense against L. interrogans infection. Modulating the structure and function of the gut microbiota may provide new individualized preventative strategies for the control of leptospirosis and related spirochetal infections.
CHD1L prevents lipopolysaccharide-induced hepatocellular carcinomar cell death by activating hnRNP A2/B1-nmMYLK axis
Authors: Wang Guangliang , Zhang Xiaofeng , Cheng Wei , Mo Yanxuan , Chen Juan , Cao Zhiming , Chen Xiaogang , Cui Huiqin , Liu Shanshan , Huang Li , Liu Ming , Ma Lei , Ma Ning-Fang 
Published: September 2021

AbstractChromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L) has been characterized to be a driver gene in hepatocellular carcinoma (HCC). However, the intrinsic connections between CHD1L and intestinal dysbacteriosis-related inflammation reaction in HCC progression remain incompletely understood. In this study, a specific correlation between CHD1L and nonmuscle isoform of myosin light chain kinase (nmMLCK/nmMYLK), a newly identified molecule associated NF-κB signaling transduction, was disclosed in HCC. CHD1L promotes nmMYLK expression and prevents lipopolysaccharide (LPS) induced tumor cell death. In vitro experiment demonstrated that overexpressed nmMYLK is essential for CHD1L to maintain HCC cell alive, while knocking down nmMYLK significantly attenuate the oncogenic roles of CHD1L. Mechanism analysis revealed that nmMYLK can prevent Caspase-8 from combining with MyD88, an important linker of TLRs signaling pathway, while, knocking down nmMYLK facilitate the MyD88 combines with Caspase-8 and lead to the proteolytic cascade of Caspase as well as the consequent cell apoptosis. Mechanism analysis showed that CHD1L promotes the nmMYLK expression potentially through upregulating the heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1) expression, which can bind to myosin light chain kinase (MYLK) pre-mRNA and lead to the regnant translation of nmMYLK. In summary, this work characterizes a previously unknown role of CHD1L in preventing LPS-induced tumor cell death through activating hnRNP A2/B1-nmMYLK axis. Further inhibition of CHD1L and its downstream signaling could be a novel promising strategy in HCC treatment.
Circular RNA hsa_circ_0043280 inhibits cervical cancer tumor growth and metastasis via miR-203a-3p/PAQR3 axis
Authors: Zhang Chunyu , Liu Pan , Huang Jiaming , Liao Yuandong , Pan Chaoyun , Liu Junxiu , Du Qiqiao , Liu Tianyu , Shang Chunliang , Ooi Shiyin , Chen Run , Xia Meng , Jiang Hongye , Xu Manman , Zou Qiaojian , Zhou Yijia , Huang Hua , Pan Yuwen , Yuan Li , Wang Wei , Yao Shuzhong 
Published: September 2021

AbstractCircular RNAs (circRNAs) are known to act as key regulators in a variety of malignancies. However, the role of circRNAs in cervical cancer (CCa) remains largely unknown. Herein, we demonstrated that a circRNA derived from the TADA2A gene (hsa_circ_0043280) was significantly downregulated in CCa and that this reduction in expression was correlated with a poor prognosis. Furthermore, our results demonstrated that hsa_circ_0043280 functions as a tumor suppressor to inhibit tumor growth and metastasis in CCa. Mechanistically, hsa_circ_0043280 competitively sponges miR-203a-3p and prevents miR-203a-3p from reducing the levels of PAQR3. Collectively, our results demonstrate that hsa_circ_0043280 plays a pivotal role in the development and metastasis of CCa, thus suggesting that hsa_circ_0043280 has significant potential as a prognostic biomarker and a therapeutic target for CCa.
Inhibition of DNMT-1 alleviates ferroptosis through NCOA4 mediated ferritinophagy during diabetes myocardial ischemia/reperfusion injury
Authors: Li Wenyuan , Li Wei , Wang Yao , Leng Yan , Xia Zhongyuan 
Published: September 2021

AbstractThe purpose of this study was to investigate whether inhibition of DNA (cytosine-5)-methyltransferase 1 (DNMT-1) alleviated ferroptosis through nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy during diabetes myocardial (DM) ischemia/reperfusion (I/R) injury (IRI). Rat DM + sham (DS), I/R, and DM + I/R (DIR), H9c2 cell high glucose (HG), hypoxia reoxygenation (H/R), and high-glucose hypoxia reoxygenation (HH/R) models were established. DNMT-1 inhibitor 5-Aza-2’-deoxycytidine (5-aza-CdR) was administered to rat and cell models. The protein level of DNMT-1, NCOA4, FTH, GPX4, Beclin-1, and P62 was detected by western blotting. Compared with normal sham (NS) group, myocardial tissue was injured in DS and I/R models. The level of DNMT-1, NCOA4, and ferroptosis was increased. Moreover, the cell injury was more serious in rat DIR or HH/R model. 5-Aza-CdR could reduce NCOA4-mediated ferritinophagy and myocardial injury in DIR and HH/R models. Moreover, the siRNA for NCOA4 could also reduce the level of ferritinophagy and cell injury in HH/R model. 5-Aza-CdR enhanced the protective effect for NCOA4-siRNA in the process of cell injury. Inhibition of DNMT-1 could reduce ferroptosis during DIR, which the NCOA4-mediated ferritinophagy might be regulated.
Social motility of biofilm-like microcolonies in a gliding bacterium
Authors: Li Chao , Hurley Amanda , Hu Wei , Warrick Jay W. , Lozano Gabriel L. , Ayuso Jose M. , Pan Wenxiao , Handelsman Jo , Beebe David J. 
Published: September 2021

AbstractBacterial biofilms are aggregates of surface-associated cells embedded in an extracellular polysaccharide (EPS) matrix, and are typically stationary. Studies of bacterial collective movement have largely focused on swarming motility mediated by flagella or pili, in the absence of a biofilm. Here, we describe a unique mode of collective movement by a self-propelled, surface-associated biofilm-like multicellular structure. Flavobacterium johnsoniae cells, which move by gliding motility, self-assemble into spherical microcolonies with EPS cores when observed by an under-oil open microfluidic system. Small microcolonies merge, creating larger ones. Microscopic analysis and computer simulation indicate that microcolonies move by cells at the base of the structure, attached to the surface by one pole of the cell. Biochemical and mutant analyses show that an active process drives microcolony self-assembly and motility, which depend on the bacterial gliding apparatus. We hypothesize that this mode of collective bacterial movement on solid surfaces may play potential roles in biofilm dynamics, bacterial cargo transport, or microbial adaptation. However, whether this collective motility occurs on plant roots or soil particles, the native environment for F. johnsoniae, is unknown.
Brief segments of neurophysiological activity enable individual differentiation
Authors: da Silva Castanheira Jason , Orozco Perez Hector Domingo , Misic Bratislav , Baillet Sylvain 
Published: September 2021

AbstractLarge, openly available datasets and current analytic tools promise the emergence of population neuroscience. The considerable diversity in personality traits and behaviour between individuals is reflected in the statistical variability of neural data collected in such repositories. Recent studies with functional magnetic resonance imaging (fMRI) have concluded that patterns of resting-state functional connectivity can both successfully distinguish individual participants within a cohort and predict some individual traits, yielding the notion of an individual’s neural fingerprint. Here, we aim to clarify the neurophysiological foundations of individual differentiation from features of the rich and complex dynamics of resting-state brain activity using magnetoencephalography (MEG) in 158 participants. We show that akin to fMRI approaches, neurophysiological functional connectomes enable the differentiation of individuals, with rates similar to those seen with fMRI. We also show that individual differentiation is equally successful from simpler measures of the spatial distribution of neurophysiological spectral signal power. Our data further indicate that differentiation can be achieved from brain recordings as short as 30 seconds, and that it is robust over time: the neural fingerprint is present in recordings performed weeks after their baseline reference data was collected. This work, thus, extends the notion of a neural or brain fingerprint to fast and large-scale resting-state electrophysiological dynamics.
Conserved ancestral tropical niche but different continental histories explain the latitudinal diversity gradient in brush-footed butterflies
Authors: Chazot Nicolas , Condamine Fabien L. , Dudas Gytis , Peña Carlos , Kodandaramaiah Ullasa , Matos-Maraví Pável , Aduse-Poku Kwaku , Elias Marianne , Warren Andrew D. , Lohman David J. , Penz Carla M. , DeVries Phil , Fric Zdenek F. , Nylin Soren , Müller Chris , Kawahara Akito Y. , Silva-Brandão Karina L. , Lamas Gerardo , Kleckova Irena , Zubek Anna , Ortiz-Acevedo Elena , Vila Roger , Vane-Wright Richard I. , Mullen Sean P. , Jiggins Chris D. , Wheat Christopher W. , Freitas Andre V. L. , Wahlberg Niklas 
Published: September 2021

AbstractThe global increase in species richness toward the tropics across continents and taxonomic groups, referred to as the latitudinal diversity gradient, stimulated the formulation of many hypotheses to explain the underlying mechanisms of this pattern. We evaluate several of these hypotheses to explain spatial diversity patterns in a butterfly family, the Nymphalidae, by assessing the contributions of speciation, extinction, and dispersal, and also the extent to which these processes differ among regions at the same latitude. We generate a time-calibrated phylogeny containing 2,866 nymphalid species (~45% of extant diversity). Neither speciation nor extinction rate variations consistently explain the latitudinal diversity gradient among regions because temporal diversification dynamics differ greatly across longitude. The Neotropical diversity results from low extinction rates, not high speciation rates, and biotic interchanges with other regions are rare. Southeast Asia is also characterized by a low speciation rate but, unlike the Neotropics, is the main source of dispersal events through time. Our results suggest that global climate change throughout the Cenozoic, combined with tropical niche conservatism, played a major role in generating the modern latitudinal diversity gradient of nymphalid butterflies.
SPOP mutation induces DNA methylation via stabilizing GLP/G9a
Authors: Zhang Jianong , Gao Kun , Xie Hongyan , Wang Dejie , Zhang Pingzhao , Wei Ting , Yan Yuqian , Pan Yunqian , Ye Wenbin , Chen Huifen , Shi Qing , Li Yao , Zhao Shi-min , Hou Xiaonan , Weroha Saravut J. , Wang Yuzhuo , Zhang Jun , Karnes R. Jeffrey , He Housheng Hansen , Wang Liguo , Wang Chenji , Huang Haojie 
Published: September 2021

AbstractMutations in SPOP E3 ligase gene are reportedly associated with genome-wide DNA hypermethylation in prostate cancer (PCa) although the underlying mechanisms remain elusive. Here, we demonstrate that SPOP binds and promotes polyubiquitination and degradation of histone methyltransferase and DNMT interactor GLP. SPOP mutation induces stabilization of GLP and its partner protein G9a and aberrant upregulation of global DNA hypermethylation in cultured PCa cells and primary PCa specimens. Genome-wide DNA methylome analysis shows that a subset of tumor suppressor genes (TSGs) including FOXO3, GATA5, and NDRG1, are hypermethylated and downregulated in SPOP-mutated PCa cells. DNA methylation inhibitor 5-azacytidine effectively reverses expression of the TSGs examined, inhibits SPOP-mutated PCa cell growth in vitro and in mice, and enhances docetaxel anti-cancer efficacy. Our findings reveal the GLP/G9a-DNMT module as a mediator of DNA hypermethylation in SPOP-mutated PCa. They suggest that SPOP mutation could be a biomarker for effective treatment of PCa with DNA methylation inhibitor alone or in combination with taxane chemotherapeutics.
Unraveling the functional role of DNA demethylation at specific promoters by targeted steric blockage of DNA methyltransferase with CRISPR/dCas9
Authors: Sapozhnikov Daniel M. , Szyf Moshe 
Published: September 2021

AbstractDespite four decades of research to support the association between DNA methylation and gene expression, the causality of this relationship remains unresolved. Here, we reaffirm that experimental confounds preclude resolution of this question with existing strategies, including recently developed CRISPR/dCas9 and TET-based epigenetic editors. Instead, we demonstrate a highly effective method using only nuclease-dead Cas9 and guide RNA to physically block DNA methylation at specific targets in the absence of a confounding flexibly-tethered enzyme, thereby enabling the examination of the role of DNA demethylation per se in living cells, with no evidence of off-target activity. Using this method, we probe a small number of inducible promoters and find the effect of DNA demethylation to be small, while demethylation of CpG-rich FMR1 produces larger changes in gene expression. This method could be used to reveal the extent and nature of the contribution of DNA methylation to gene regulation.
A general approach to protein folding using thermostable exoshells
Authors: Sadeghi Samira , Deshpande Siddharth , Vallerinteavide Mavelli Girish , Aksoyoglu Alphan , Bafna Jayesh , Winterhalter Mathias , Kini R. Manjunatha , Lane David P. , Drum Chester L. 
Published: September 2021

AbstractIn vitro protein folding is a complex process which often results in protein aggregation, low yields and low specific activity. Here we report the use of nanoscale exoshells (tES) to provide complementary nanoenvironments for the folding and release of 12 highly diverse protein substrates ranging from small protein toxins to human albumin, a dimeric protein (alkaline phosphatase), a trimeric ion channel (Omp2a) and the tetrameric tumor suppressor, p53. These proteins represent a unique diversity in size, volume, disulfide linkages, isoelectric point and multi versus monomeric nature of their functional units. Protein encapsulation within tES increased crude soluble yield (3-fold to >100-fold), functional yield (2-fold to >100-fold) and specific activity (3-fold to >100-fold) for all the proteins tested. The average soluble yield was 6.5 mg/100 mg of tES with charge complementation between the tES internal cavity and the protein substrate being the primary determinant of functional folding. Our results confirm the importance of nanoscale electrostatic effects and provide a solution for folding proteins in vitro.
Zebrafish capable of generating future state prediction error show improved active avoidance behavior in virtual reality
Authors: Torigoe Makio , Islam Tanvir , Kakinuma Hisaya , Fung Chi Chung Alan , Isomura Takuya , Shimazaki Hideaki , Aoki Tazu , Fukai Tomoki , Okamoto Hitoshi 
Published: September 2021

AbstractAnimals make decisions under the principle of reward value maximization and surprise minimization. It is still unclear how these principles are represented in the brain and are reflected in behavior. We addressed this question using a closed-loop virtual reality system to train adult zebrafish for active avoidance. Analysis of the neural activity of the dorsal pallium during training revealed neural ensembles assigning rules to the colors of the surrounding walls. Additionally, one third of fish generated another ensemble that becomes activated only when the real perceived scenery shows discrepancy from the predicted favorable scenery. The fish with the latter ensemble escape more efficiently than the fish with the former ensembles alone, even though both fish have successfully learned to escape, consistent with the hypothesis that the latter ensemble guides zebrafish to take action to minimize this prediction error. Our results suggest that zebrafish can use both principles of goal-directed behavior, but with different behavioral consequences depending on the repertoire of the adopted principles.
Reconfigurable Stochastic neurons based on tin oxide/MoS2 hetero-memristors for simulated annealing and the Boltzmann machine
Authors: Yan Xiaodong , Ma Jiahui , Wu Tong , Zhang Aoyang , Wu Jiangbin , Chin Matthew , Zhang Zhihan , Dubey Madan , Wu Wei , Chen Mike Shuo-Wei , Guo Jing , Wang Han 
Published: September 2021

AbstractNeuromorphic hardware implementation of Boltzmann Machine using a network of stochastic neurons can allow non-deterministic polynomial-time (NP) hard combinatorial optimization problems to be efficiently solved. Efficient implementation of such Boltzmann Machine with simulated annealing desires the statistical parameters of the stochastic neurons to be dynamically tunable, however, there has been limited research on stochastic semiconductor devices with controllable statistical distributions. Here, we demonstrate a reconfigurable tin oxide (SnOx)/molybdenum disulfide (MoS2) heterogeneous memristive device that can realize tunable stochastic dynamics in its output sampling characteristics. The device can sample exponential-class sigmoidal distributions analogous to the Fermi-Dirac distribution of physical systems with quantitatively defined tunable “temperature” effect. A BM composed of these tunable stochastic neuron devices, which can enable simulated annealing with designed “cooling” strategies, is conducted to solve the MAX-SAT, a representative in NP-hard combinatorial optimization problems. Quantitative insights into the effect of different “cooling” strategies on improving the BM optimization process efficiency are also provided.