bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome analysis of ankylosed primary molars with infraocclusion
Authors: Tong Annie , Chow Yuh-Lit , Xu Katie , Hardiman Rita , Schneider Paul , Tan Seong-Seng 
Published: February 2020

AbstractPrimary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address this, RNA sequencing was used to generate transcriptomes of furcal bone from infraoccluded (n = 7) and non-infraoccluded (n = 9) primary second molars, all without succeeding biscuspids. Of the 18 529 expressed genes, 432 (2.3%) genes were differentially expressed between the two groups (false discovery rate < 0.05). Hierarchical clustering and principal component analysis showed clear separation in gene expression between infraoccluded and non-infraoccluded samples. Pathway analyses indicated that molar ankylosis is associated with the expression of genes consistent with the cellular inflammatory response and epithelial cell turnover. Independent validation using six expressed genes by immunohistochemical analysis demonstrated that the corresponding proteins are strongly expressed in the developing molar tooth germ, in particular the dental follicle and inner enamel epithelium. The descendants of these structures include the periodontal ligament, cementum, bone and epithelial rests of Malassez; tissues that are central to the ankylotic process. We therefore propose that ankylosis involves an increased inflammatory response associated with disruptions to the developmental remnants of the dental follicle and epithelial rests of Malassez.
Both IDO1 and TDO contribute to the malignancy of gliomas via the Kyn–AhR–AQP4 signaling pathway
Authors: Du Lisha , Xing Zikang , Tao Bangbao , Li Tianqi , Yang Dan , Li Weirui , Zheng Yuanting , Kuang Chunxiang , Yang Qing 
Published: February 2020

AbstractIndoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan 2,3-dioxygenase (TDO) initiate the first step of the kynurenine pathway (KP), leading to the transformation of l-tryptophan (Trp) into l-kynurenine (Kyn) and other downstream metabolites. Kyn is known as an endogenous ligand of the aryl hydrocarbon receptor (AhR). Activation of AhR through TDO-derived Kyn is a novel mechanism to support tumor growth in gliomas. However, the role of IDO1 and IDO2 in this mechanism is still unknown. Herein, by using clinical samples, we found that the expression and activity of IDO1 and/or TDO (IDO1/TDO) rather than IDO2 were positively correlated with the pathologic grades of gliomas. The expression of IDO1/TDO rather than IDO2 was positively correlated with the Ki67 index and overall survival. The expression of IDO1/TDO was positively correlated with the expression of aquaporin 4 (AQP4), implying the potential involvement of IDO1/TDO in glioma cell motility. Mechanistically, we found that IDO1/TDO accounted for the release of Kyn, which activated AhR to promote cell motility via the Kyn–AhR–AQP4 signaling pathway in U87MG glioma cells. RY103, an IDO1/TDO dual inhibitor, could block the IDO1/TDO–Kyn–AhR–AQP4 signaling pathway and exert anti-glioma effects in GL261 orthotopic glioma mice. Together, our results showed that the IDO1/TDO–Kyn–AhR–AQP4 signaling pathway is a new mechanism underlying the malignancy of gliomas, and suggest that both IDO1 and TDO might be valuable therapeutic targets for gliomas.
Laminar flow inhibits the Hippo/YAP pathway via autophagy and SIRT1-mediated deacetylation against atherosclerosis
Authors: Yuan Ping , Hu Qiongying , He Xuemei , Long Yang , Song Xueqin , Wu Fei , He Yanzheng , Zhou Xiangyu 
Published: February 2020

AbstractAtherosclerosis is a multifactorial disease of the vasculature, and shear stress is a crucial regulator of its process. Disturbed flow promotes atherosclerotic effects, while laminar flow has a protective action on the endothelium. Hippo/YAP is a major cascade that senses various mechanical cues and mediates the expression of pro-inflammatory genes. However, the mechanism modulating the transcription factor YAP in response to different patterns of blood flow remains unclear. In this study, we provide evidence that shear stress modulates YAP activity via autophagy in endothelial cells. Laminar flow promoted the expression of the autophagic markers BECLIN 1 and LC3II/LC3I. Autophagy blockade using a chemical inhibitor repressed YAP degradation under laminar flow. Conversely, the induction of autophagy under disturbed flow partially antagonized the nuclear import and transcriptional activation of YAP. In parallel, laminar flow led to the increased expression of SIRT1 protein, a NAD+-dependent deacetylase. Further investigation showed that SIRT1-mediated YAP deacetylation. The forced expression of SIRT1 under disturbed flow effectively attenuated YAP activation and nuclear accumulation, thereby downregulating the expression of pro-inflammatory genes. In atheroprone vessels of mice receiving rapamycin to induce autophagy, the enhanced expression of SIRT1 was observed together with YAP repression. Altogether, these results show that endothelial autophagy and SIRT1 expression induced by laminar flow contribute to the inhibition of Hippo/YAP signaling and interrupt atherosclerotic plaque formation.
Deguelin suppresses non-small cell lung cancer by inhibiting EGFR signaling and promoting GSK3β/FBW7-mediated Mcl-1 destabilization
Authors: Gao Feng , Yu Xinfang , Li Ming , Zhou Li , Liu Wenbin , Li Wei , Liu Haidan 
Published: February 2020

AbstractActivating mutations of epidermal growth factor receptor (EGFR) play crucial roles in the oncogenesis of human non-small cell lung cancer (NSCLC). By screening 79 commercially available natural products, we found that the natural compound deguelin exhibited a profound anti-tumor effect on NSCLC via directly down-regulating of EGFR-signaling pathway. Deguelin potently inhibited in vitro EGFR kinase activity of wild type (WT), exon 19 deletion, and L858R/T790M-mutated EGFR. The in silico docking study indicated that deguelin was docked into the ATP-binding pocket of EGFRs. By suppression of EGFR signaling, deguelin inhibited anchorage-dependent, and independent growth of NSCLC cell lines, and significantly delayed tumorigenesis in vivo. Further study showed that deguelin inhibited EGFR and downstream kinase Akt, which resulted in the activation of GSK3β and eventually enhanced Mcl-1 phosphorylation at S159. Moreover, deguelin promoted the interaction between Mcl-1 and E3 ligase SCFFBW7, which enhanced FBW7-mediated Mcl-1 ubiquitination and degradation. Additionally, phosphorylation of Mcl-1 by GSK3β is a prerequisite for FBW7-mediated Mcl-1 destruction. Depletion or pharmacological inactivation of GSK3β compromised deguelin-induced Mcl-1 ubiquitination and reduction. Taken together, our data indicate that enhancement of ubiquitination-dependent Mcl-1 turnover might be a promising approach for cancer treatment.
Immuno-genomic landscape of osteosarcoma
Authors: Wu Chia-Chin , Beird Hannah C. , Andrew Livingston J. , Advani Shailesh , Mitra Akash , Cao Shaolong , Reuben Alexandre , Ingram Davis , Wang Wei-Lien , Ju Zhenlin , Hong Leung Cheuk , Lin Heather , Zheng Youyun , Roszik Jason , Wang Wenyi , Patel Shreyaskumar , Benjamin Robert S. , Somaiah Neeta , Conley Anthony P. , Mills Gordon B. , Hwu Patrick , Gorlick Richard , Lazar Alexander , Daw Najat C. , Lewis Valerae , Futreal P. Andrew 
Published: February 2020

AbstractLimited clinical activity has been seen in osteosarcoma (OS) patients treated with immune checkpoint inhibitors (ICI). To gain insights into the immunogenic potential of these tumors, we conducted whole genome, RNA, and T-cell receptor sequencing, immunohistochemistry and reverse phase protein array profiling (RPPA) on OS specimens from 48 pediatric and adult patients with primary, relapsed, and metastatic OS. Median immune infiltrate level was lower than in other tumor types where ICI are effective, with concomitant low T-cell receptor clonalities. Neoantigen expression in OS was lacking and significantly associated with high levels of nonsense-mediated decay (NMD). Samples with low immune infiltrate had higher number of deleted genes while those with high immune infiltrate expressed higher levels of adaptive resistance pathways.PARP2expression levels were significantly negatively associated with the immune infiltrate. Together, these data reveal multiple immunosuppressive features of OS and suggest immunotherapeutic opportunities in OS patients.
Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior
Authors: Bicks Lucy K. , Yamamuro Kazuhiko , Flanigan Meghan E. , Kim Julia Minjung , Kato Daisuke , Lucas Elizabeth K. , Koike Hiroyuki , Peng Michelle S. , Brady Daniel M. , Chandrasekaran Sandhya , Norman Kevin J. , Smith Milo R. , Clem Roger L. , Russo Scott J. , Akbarian Schahram , Morishita Hirofumi 
Published: February 2020

AbstractSocial isolation during the juvenile critical window is detrimental to proper functioning of the prefrontal cortex (PFC) and establishment of appropriate adult social behaviors. However, the specific circuits that undergo social experience-dependent maturation to regulate social behavior are poorly understood. We identify a specific activation pattern of parvalbumin-positive interneurons (PVIs) in dorsal-medial PFC (dmPFC) prior to an active bout, or a bout initiated by the focal mouse, but not during a passive bout when mice are explored by a stimulus mouse. Optogenetic and chemogenetic manipulation reveals that brief dmPFC-PVI activation triggers an active social approach to promote sociability. Juvenile social isolation decouples dmPFC-PVI activation from subsequent active social approach by freezing the functional maturation process of dmPFC-PVIs during the juvenile-to-adult transition. Chemogenetic activation of dmPFC-PVI activity in the adult animal mitigates juvenile isolation-induced social deficits. Therefore, social experience-dependent maturation of dmPFC-PVI is linked to long-term impacts on social behavior.
Cysteine-specific protein multi-functionalization and disulfide bridging using 3-bromo-5-methylene pyrrolones
Authors: Zhang Yingqian , Zang Chuanlong , An Guoce , Shang Mengdi , Cui Zenghui , Chen Gong , Xi Zhen , Zhou Chuanzheng 
Published: February 2020

AbstractMany reagents have been developed for cysteine-specific protein modification. However, few of them allow for multi-functionalization of a single Cys residue and disulfide bridging bioconjugation. Herein, we report 3-bromo-5-methylene pyrrolones (3Br-5MPs) as a simple, robust, and versatile class of reagents for cysteine-specific protein modification. These compounds can be facilely synthesized via a one-pot mild reaction and they show comparable tagging efficiency but higher cysteine specificity than the maleimide counterparts. The addition of cysteine to 3Br-5MPs generates conjugates that are amenable to secondary addition by another thiol or cysteine, making 3Br-5MPs valuable for multi-functionalization of a single cysteine and disulfide bridging bioconjugation. The labeling reaction and subsequent treatments are mild enough to produce stable and active protein conjugates for biological applications.
Pan-cancer characterization of immune-related lncRNAs identifies potential oncogenic biomarkers
Authors: Li Yongsheng , Jiang Tiantongfei , Zhou Weiwei , Li Junyi , Li Xinhui , Wang Qi , Jin Xiaoyan , Yin Jiaqi , Chen Liuxin , Zhang Yunpeng , Xu Juan , Li Xia 
Published: February 2020

AbstractLong noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression and they play fundamental roles in immune regulation. Here we introduce an integrated algorithm, ImmLnc, for identifying lncRNA regulators of immune-related pathways. We comprehensively chart the landscape of lncRNA regulation in the immunome across 33 cancer types and show that cancers with similar tissue origin are likely to share lncRNA immune regulators. Moreover, the immune-related lncRNAs are likely to show expression perturbation in cancer and are significantly correlated with immune cell infiltration. ImmLnc can help prioritize cancer-related lncRNAs and further identify three molecular subtypes (proliferative, intermediate, and immunological) of non-small cell lung cancer. These subtypes are characterized by differences in mutation burden, immune cell infiltration, expression of immunomodulatory genes, response to chemotherapy, and prognosis. In summary, the ImmLnc pipeline and the resulting data serve as a valuable resource for understanding lncRNA function and to advance identification of immunotherapy targets.
Purging of highly deleterious mutations through severe bottlenecks in Alpine ibex
Authors: Grossen Christine , Guillaume Frédéric , Keller Lukas F. , Croll Daniel 
Published: February 2020

AbstractHuman activity has caused dramatic population declines in many wild species. The resulting bottlenecks have a profound impact on the genetic makeup of a species with unknown consequences for health. A key genetic factor for species survival is the evolution of deleterious mutation load, but how bottleneck strength and mutation load interact lacks empirical evidence. We analyze 60 complete genomes of six ibex species and the domestic goat. We show that historic bottlenecks rather than the current conservation status predict levels of genome-wide variation. By analyzing the exceptionally well-characterized population bottlenecks of the once nearly extinct Alpine ibex, we find genomic evidence of concurrent purging of highly deleterious mutations but accumulation of mildly deleterious mutations. This suggests that recolonization bottlenecks induced both relaxed selection and purging, thus reshaping the landscape of deleterious mutation load. Our findings highlight that even populations of ~1000 individuals can accumulate mildly deleterious mutations. Conservation efforts should focus on preventing population declines below such levels to ensure long-term survival of species.
Structural ensemble of a glutamate transporter homologue in lipid nanodisc environment
Authors: Arkhipova Valentina , Guskov Albert , Slotboom Dirk J. 
Published: February 2020

AbstractGlutamate transporters are cation-coupled secondary active membrane transporters that clear the neurotransmitter L-glutamate from the synaptic cleft. These transporters are homotrimers, with each protomer functioning independently by an elevator-type mechanism, in which a mobile transport domain alternates between inward- and outward-oriented states. Using single-particle cryo-EM we have determined five structures of the glutamate transporter homologue GltTk, a Na+- L-aspartate symporter, embedded in lipid nanodiscs. Dependent on the substrate concentrations used, the protomers of the trimer adopt a variety of asymmetrical conformations, consistent with the independent movement. Six of the 15 resolved protomers are in a hitherto elusive state of the transport cycle in which the inward-facing transporters are loaded with Na+ ions. These structures explain how substrate-leakage is prevented – a strict requirement for coupled transport. The belt protein of the lipid nanodiscs bends around the inward oriented protomers, suggesting that membrane deformations occur during transport.
Daytime symptoms of chronic obstructive pulmonary disease: a systematic review
Authors: Tsiligianni Ioanna , Kocks Janwillem W. H. 
Published: February 2020

AbstractThere is no single source of compiled data on symptoms experienced by patients with chronic obstructive pulmonary disease (COPD) when awake and active throughout the day. The aim of this systematic review was to evaluate the prevalence, variability, and burden (i.e., bothersomeness and/or intensity), and the impact of daytime COPD symptoms on other outcomes. The review also evaluated the impact of interventions and the measures/tools used to assess daytime COPD symptoms in patients. A systematic literature search was conducted using the primary search terms “COPD”, “symptoms”, and “daytime” in EMBASE®, MEDLINE®, MEDLINE® In-Process, and CENTRAL in 2016, followed by an additional search in 2018 to capture any new literature that was published since the last search. Fifty-six articles were included in the review. The accumulated evidence indicated that the symptomatic burden of COPD appears greatest in the morning, particularly upon waking, and that these morning symptoms have a substantial impact on patients’ ability to function normally through the day; they also worsen quality of life. A wide variety of tools were used to evaluate symptoms across the studies. The literature also confirmed the importance of pharmacotherapy in the management of daytime COPD symptoms, and in helping normalize daily functioning. More research is needed to better understand how COPD symptoms impact daily functioning and to evaluate COPD symptoms at well-defined periods throughout the day, using validated and uniform measures/tools. This will help clinicians to better define patients’ needs and take appropriate action.
Hyphal network whole field imaging allows for accurate estimation of anastomosis rates and branching dynamics of the filamentous fungus Podospora anserina
Authors: Dikec J. , Olivier A. , Bobée C. , D’Angelo Y. , Catellier R. , David P. , Filaine F. , Herbert S. , Lalanne Ch. , Lalucque H. , Monasse L. , Rieu M. , Ruprich-Robert G. , Véber A. , Chapeland-Leclerc F. , Herbert E. 
Published: February 2020

AbstractThe success of filamentous fungi in colonizing most natural environments can be largely attributed to their ability to form an expanding interconnected network, the mycelium, or thallus, constituted by a collection of hyphal apexes in motion producing hyphae and subject to branching and fusion. In this work, we characterize the hyphal network expansion and the structure of the fungus Podospora anserina under controlled culture conditions. To this end, temporal series of pictures of the network dynamics are produced, starting from germinating ascospores and ending when the network reaches a few centimeters width, with a typical image resolution of several micrometers. The completely automated image reconstruction steps allow an easy post-processing and a quantitative analysis of the dynamics. The main features of the evolution of the hyphal network, such as the total length L of the mycelium, the number of “nodes” (or crossing points) N and the number of apexes A, can then be precisely quantified. Beyond these main features, the determination of the distribution of the intra-thallus surfaces (Si) and the statistical analysis of some local measures of N, A and L give new insights on the dynamics of expanding fungal networks. Based on these results, we now aim at developing robust and versatile discrete/continuous mathematical models to further understand the key mechanisms driving the development of the fungus thallus.
Sustainability of spatially distributed bacteria-phage systems
Authors: Eriksen Rasmus Skytte , Mitarai Namiko , Sneppen Kim 
Published: February 2020

AbstractVirulent phages can expose their bacterial hosts to devastating epidemics, in principle leading to complete elimination of their hosts. Although experiments indeed confirm a large reduction of susceptible bacteria, there are no reports of complete extinctions. We here address this phenomenon from the perspective of spatial organization of bacteria and how this can influence the final survival of them. By modelling the transient dynamics of bacteria and phages when they are introduced into an environment with finite resources, we quantify how time delayed lysis, the spatial separation of initial bacterial positions, and the self-protection of bacteria growing in spherical colonies favour bacterial survival. Our results suggest that spatial structures on the millimetre and submillimetre scale play an important role in maintaining microbial diversity.
Equilibrium Thermodynamic Properties of Aqueous Solutions of Ionic Liquid 1-Ethyl-3-Methylimidazolium Methanesulfonate [EMIM][MeSO3]
Authors: Zheng Chaolun , Zhou Jian , Pei Yong , Yang Bao 
Published: February 2020

AbstractThe ionic liquid 1-ethyl-3-methylimidazolium methanesulfonate ([EMIM][MeSO3]) has been considered as a promising alternative desiccant to triethylene glycol and lithium bromide commonly used in the industry. In this paper, the water activity coefficient of this binary system was measured from 303 K to 363 K with water concentration from 18% to 92%. The interaction energies between the ionic liquid molecules ($${g}_{22}$$g22) and between the ionic liquid and water molecules ($${g}_{12}$$g12) for the [EMIM][MeSO3]/water binary system were determined from the water activity coefficient data using the Non-Random Two-Liquid (NRTL) model. The magnitude of the interaction energy between the [EMIM][MeSO3] and water molecules ($${g}_{12}$$g12) was found to be in the range of 45~49 kJ/mol, which was about 20% larger than that between the water molecules ($${g}_{11}$$g11) in the [EMIM][MeSO3]/water system. The large ($${g}_{12}$$g12) can explain many observed macroscopic thermodynamic properties such as strong hygroscopicity in the ionic liquid [EMIM][MeSO3]. These interaction energies were used to determine the heat of desorption of the [EMIM][MeSO3]/water system, and the obtained heat of desorption was in good agreement with that calculated from the conventional Clausius-Clapeyron Equation.
Very high sensitivity of African rice to artificial ultraviolet-B radiation caused by genotype and quantity of cyclobutane pyrimidine dimer photolyase
Authors: Mmbando Gideon Sadikiel , Teranishi Mika , Hidema Jun 
Published: February 2020

AbstractUltraviolet-B (UVB) radiation damages plants and decreases their growth and productivity. We previously demonstrated that UVB sensitivity varies widely among Asian rice (Oryza sativaL.) cultivars and that the activity of cyclobutane pyrimidine dimer (CPD) photolyase, which repairs UVB-induced CPDs, determines UVB sensitivity. Unlike Asian rice, African rice (Oryza glaberrimaSteud. andOryza barthiiA. Chev.) has mechanisms to adapt to African climates and to protect itself against biotic and abiotic stresses. However, information about the UVB sensitivity of African rice species is largely absent. We showed that most of the African rice cultivars examined in this study were UVB-hypersensitive or even UVB-super-hypersensitive in comparison with the UVB sensitivity of AsianO. sativacultivars. The difference in UVB resistance correlated with the total CPD photolyase activity, which was determined by its activity and its cellular content. The UVB-super-hypersensitive cultivars had low enzyme activity caused by newly identified polymorphisms and low cellular CPD photolyase contents. The new polymorphisms were only found in cultivars from West Africa, particularly in those from countries believed to be centres ofO. glaberrimadomestication. This study provides new tools for improving both Asian and African rice productivity.