bluuebunny/crossref_metadata_2025_split huggingface dataset:
Productivity and the acquisition of gender
Authors: BJÖRNSDÓTTIR Sigríður Mjöll 
Published: February 2021

AbstractChildren's differing learning trajectories cross-linguistically have been at the forefront of gender acquisition research, often with conflicting results and conclusions. As a result, the source of children's different learning behaviors in gender acquisition has been unclear. I argue that children's gender acquisition is driven by the search for productive patterns. First, I provide corpus studies where the predictions of a learning model (Yang, 2016) are formulated. Second, I report the results of an elicited production task on Icelandic-speaking children (N = 26, ages 2;6-6;3 years) and adults (N = 18) that puts these predictions to test. The results suggest that Icelandic-speaking children and adults draw a categorical distinction between productive and unproductive suffixes in Icelandic gender assignment. I discuss the implications of these findings for morphological learning beyond gender acquisition.
Indigenous peoples' displacement and jaguar survival in a warming planet
Authors: Craighead Kimberly A. , Yacelga Milton 
Published: February 2021

Non-technical summaryClimate change threatens tropical forests, ecosystem services, and indigenous peoples. The effects of climate change will force the San Blas Island communities of the indigenous Guna people to relocate to one of the most extensive, intact forests in Panama. In this paper, we argue that the impacts of climate change, and the proposed resettlement, will synergistically affect the jaguar. As apex predators, jaguars are sensitive to landscape change and require intact forests with ample prey to survive. Proactively planning for the intrinsically related issues of climate change, human displacement, and jaguar conservation is a complex but essential management task.Technical summaryTropical rainforest, coastal, and island communities are on the front line of increasing temperatures and sea-level rise associated with climate change. Future impacts on the interconnectedness of biological and cultural diversity (biocultural heritage) remain unknown. We review the interplay between the impacts of climate change and the displacement of the indigenous Guna people from the San Blas Islands, the relocation back to their mainland territory, and the implications for jaguar persistence. We highlight one of the most significant challenges to using resettlement as an adaptive strategy to climate change, securing a location where the Guna livelihoods, traditions, and culture may continue without significant change while protecting ecosystem services (e.g. biodiversity, carbon sequestration, and water). We posit that developing management plans that strive to meet social needs without sacrificing environmental principles will meet these objectives.Social media summaryA biocultural approach increases adaptive capacity for ecological and human social systems threatened by climate change.
Seasonal and Geographical Variability of the Martian Ionosphere From Mars Express Observations
Authors: González‐Galindo F. , Eusebio D. , Němec F. , Peter K. , Kopf A. , Tellmann S. , Paetzold M. 
Published: February 2021

AbstractWe study the seasonal and geographical variability of the peak electron density and the altitude of the main ionospheric peak at Mars. For this purpose, we use the data obtained by the ESA Mars Express mission, namely by the radar MARSIS and the radio occultation experiment MaRS. The accumulation of data during the long lifetime of Mars Express provides for the first time an almost complete seasonal and geographical coverage. We first remove the dominant variability factors affecting the main ionospheric peak, namely the effect of changes in the solar zenith angle (SZA), and the changes in the solar ultraviolet radiation output at the Sun. When averaging results obtained at all latitudes, we find that the seasonal variation of both the peak density and the peak altitude can be well reproduced by sinusoidal functions with amplitudes about 8%–9% of the annually averaged peak density, and between 8 and 9.5 km for the peak altitude. We also find elevated peak electron densities in the region of strong crustal fields and latitudinal asymmetries in both the peak density and altitude. Comparing the seasonal evolution of the peak altitude during Mars Year 28, a year with a global dust storm, and the rest of the years, we find that the global dust storm raised the altitude of the ionospheric peak by about 10–15 km.
Geological Factors Impacted Cadmium Availability and use as an Alternative Cofactor for Zinc in the Carbon Fixation Pathways of Marine Diatoms
Authors: Srivastava Naman , Spielman Stephanie J. , Morrison Shaunna M. , Moore Eli K. 
Published: February 2021

AbstractTransition metal cofactors are crucial for many biological processes. Despite being primarily considered to be toxic, the transition metal cadmium (Cd) was discovered to be a substitute cofactor for zinc (Zn) in photosynthetic carbon fixation pathways of marine diatoms. However, it is not known how conditions in the geosphere impacted Cd availability and its incorporation as an alternative metal cofactor for phytoplankton. We employed mineral chemistry network analysis to investigate which geochemical factors may have influenced the availability of Cd and Zn during the putative time period that the alternative Cd‐based pathway evolved. Our results show that Zn minerals are more chemically diverse than are Cd minerals, but Zn‐ and Cd‐containing minerals have similar network centrality values when specifically considering sulfur (S)‐containing species. Cadmium and Zn sulfides are the most common Cd‐ and Zn‐containing mineral species over the past 500 million years. In particular, the Cd and Zn sulfides, respectively greenockite and sphalerite, were highly abundant during this time period. Furthermore, S‐containing Cd and Zn minerals are commonly co‐located in geologic time, allowing them to be weathered and transported to the ocean in tandem, rather than from separate sources. We suggest that the simultaneous weathering of Cd and Zn sulfides allowed for Cd to be a bioavailable direct substitute for Zn in protein complexes during periods of Zn depletion. The biogeochemical cycles of Zn and Cd exemplify the importance of the coevolution of the geosphere and biosphere in shaping primary production in the modern ocean.
Designing With Information Feedbacks: Forecast Informed Reservoir Sizing and Operation
Authors: Bertoni F. , Giuliani M. , Castelletti A. , Reed P. M. 
Published: February 2021

AbstractThe value of streamflow forecasts to inform water infrastructure operations has been extensively studied. Yet, their value in informing infrastructure design is still unexplored. In this work, we investigate how dam design is shaped by information feedbacks supporting the implementation of flexible operating policies informed by streamflow forecasts to enable the design of less costly reservoirs relative to alternatives that do not rely on forecast information. Our approach initially explores the maximum potential gain attainable by searching and using the most valuable forecast information and lead time. We then analyze the results? sensitivities relative to existing and synthetic biased forecasts. We demonstrate our approach through an ex post analysis of the Kariba Dam in the Zambezi River Basin. Results show that informing dam design with perfect forecasts enables attaining the same hydropower production of the existing dam, while reducing infrastructure size and associated capital costs by 20%. A forecast‐informed operation of the existing system can instead facilitate an annual average increase of 60 GWh in hydropower production. This finding, extrapolated to the new planned dams in the basin, suggests that forecast informed policies could yield power production benefits equal to 75% of the current annual electricity consumption of the Zambian agricultural sector. The use of biased forecasts substantially reduces this gain, showing that the ESP forecasts value is marginal and that informed infrastructure designs are particularly vulnerable to forecast overestimation. Advancing information feedbacks may therefore become a valuable asset for the ongoing hydropower expansion in the basin.
LncRNA SNHG1 and RNA binding protein hnRNPL form a complex and coregulate CDH1 to boost the growth and metastasis of prostate cancer
Authors: Tan Xiao , Chen Wen-bin , Lv Dao-jun , Yang Tao-wei , Wu Kai-hui , Zou Li-bin , Luo Junqi , Zhou Xu-min , Liu Guo-chang , Shu Fang-peng , Mao Xiang-ming 
Published: February 2021

AbstractThe interaction between LncRNA and RNA-binding protein (RBPs) plays an essential role in the regulation over the malignant progression of tumors. Previous studies on the mechanism of SNHG1, an emerging lncRNA, have primarily focused on the competing endogenous RNA (ceRNA) mechanism. Nevertheless, the underlying mechanism between SNHG1 and RBPs in tumors remains to be explored, especially in prostate cancer (PCa). SNHG1 expression profiles in PCa were determined through the analysis of TCGA data and tissue microarray at the RNA level. Gain- and loss-of-function experiments were performed to investigate the biological role of SNHG1 in PCa initiation and progression. RNA-seq, immunoblotting, RNA pull-down and RNA immunoprecipitation analyses were utilized to clarify potential pathways with which SNHG1 might be involved. Finally, rescue experiments were carried out to further confirm this mechanism. We found that SNHG1 was dominantly expressed in the nuclei of PCa cells and significantly upregulated in PCa patients. The higher expression level of SNHG1 was dramatically correlated with tumor metastasis and patient survival. Functionally, overexpression of SNHG1 in PCa cells induced epithelial–mesenchymal transition (EMT), accompanied by down-regulation of the epithelial marker, E-cadherin, and up-regulation of the mesenchymal marker, vimentin. Increased proliferation and migration, as well as accelerated xenograft tumor growth, were observed in SNHG1-overexpressing PCa cells, while opposite effects were achieved in SNHG1-silenced cells. Mechanistically, SNHG1 competitively interacted with hnRNPL to impair the translation of protein E-cadherin, thus activating the effect of SNHG1 on the EMT pathway, eventually promoting the metastasis of PCa. Our findings demonstrate that SNHG1 is a positive regulator of EMT activation through the SNHG1-hnRNPL-CDH1 axis. SNHG1 may serve as a novel potential therapeutic target for PCa.
LncRNA LTSCCAT promotes tongue squamous cell carcinoma metastasis via targeting the miR-103a-2-5p/SMYD3/TWIST1 axis
Authors: Liu Mo , Liu Qingwen , Fan Song , Su Feng , Jiang Chun , Cai Guanming , Wang Youyuan , Liao Guiqing , Lei Xinyuan , Chen Weixiong , Bi Junming , Cheng Weiqi , Zhao LuoDan , Ruan Yi , Li Jinsong 
Published: February 2021

AbstractAbnormal expression of long-noncoding RNA is involved in the tumorigenesis and progression of various cancers, but the potential molecular regulatory mechanisms are unclear. Microbial flora and chronic inflammation, such as periodontitis, which is associated with oral cancer, affect the occurrence and progression of tumors. Accordingly, we stimulated the tongue squamous cell carcinoma (TSCC) cell lines CAL27 and SCC15 with a low concentration of lipopolysaccharide (LPS) from Porphyromonas gingivalis (P.g) for 6 days and then performed LncRNA sequencing on P.g-LPS-treated CAL27 cells and untreated CAL27 cells. LTSCCAT was upregulated in P.g-LPS-treated CAL27 cells compared with untreated CAL27 cells. LTSCCAT induced epithelial–mesenchymal transition and promoted the invasion and metastasis of TSCC in vitro and in vivo. LncRNA LTSCCAT was upregulated in TSCC patients with periodontitis and was correlated with metastasis and poor prognosis. We predicted through an online database and confirmed by dual-luciferase reporter assays that LTSCCAT is a competitive endogenous RNA for the regulation of miR-103a-2-5p. Another dual-luciferase reporter assay confirmed that miR-103a-2-5p has a binding site at the 3′-UTR of the histone methylation transferase SMYD3 and inhibits its translation. Chromatin immunoprecipitation experiments demonstrated that SMYD3 binds directly to the promoter region of TWIST1 and promotes its transcription, which is related to H3K4 trimethylation. The effect of pcDNA/LTSCCAT on expression was attenuated by miR-103a-2-5p mimics. The RF and SVM classifier predicts that LTSCCAT can bind to SMYD3, whereas the RNA immunoprecipitation (RIP) assay confirms that it cannot. In addition, we predicted the combination of LTSCCAT and SMYD3 through software, but the RIP assay confirmed that LTSCCAT could not be combined with SMYD3. For the first time, we showed that periodontitis promotes the invasion and metastasis of TSCC and clarified the molecular mechanism of LTSCCAT to promote invasion and metastasis of TSCC, providing a potential therapeutic target for clinical treatment of TSCC.
HDAC4 promotes nasopharyngeal carcinoma progression and serves as a therapeutic target
Authors: Cheng Chun , Yang Jun , Li Si-Wei , Huang Guofu , Li Chenxi , Min Wei-Ping , Sang Yi 
Published: February 2021

AbstractHistone deacetylases (HDACs) are involved in tumor progression, and some have been successfully targeted for cancer therapy. The expression of histone deacetylase 4 (HDAC4), a class IIa HDAC, was upregulated in our previous microarray screen. However, the role of HDAC4 dysregulation and mechanisms underlying tumor growth and metastasis in nasopharyngeal carcinoma (NPC) remain elusive. Here, we first confirmed that the HDAC4 levels in primary and metastatic NPC tissues were significantly increased compared with those in normal nasopharyngeal epithelial tissues and found that high HDAC4 expression predicted a poor overall survival (OS) and progression-free survival (PFS). Functionally, HDAC4 accelerated cell cycle G1/S transition and induced the epithelial-to-mesenchymal transition to promote NPC cell proliferation, migration, and invasion in vitro, as well as tumor growth and lung metastasis in vivo. Intriguingly, knockdown of N-CoR abolished the effects of HDAC4 on the invasion and migration abilities of NPC cells. Mechanistically, HDAC3/4 binds to the E-cadherin promoter to repress E-cadherin transcription. We also showed that the HDAC4 inhibitor tasquinimod suppresses tumor growth in NPC. Thus, HDAC4 may be a potential diagnostic marker and therapeutic target in patients with NPC.
CircRILPL1 promotes muscle proliferation and differentiation via binding miR-145 to activate IGF1R/PI3K/AKT pathway
Authors: Shen Xuemei , Tang Jia , Jiang Rui , Wang Xiaogang , Yang Zhaoxin , Huang Yongzhen , Lan Xianyong , Lei Chuzhao , Chen Hong 
Published: February 2021

AbstractMany novel non-coding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in various physiological and pathological processes. The PI3K/AKT signaling pathway is important for its role in regulating skeletal muscle development. In this study, molecular and biochemical assays were used to confirm the role of miRNA-145 (miR-145) in myoblast proliferation and apoptosis. Based on sequencing data and bioinformatics analysis, we identified a new circRILPL1, which acts as a sponge for miR-145. The interactions between circRILPL1 and miR-145 were examined by bioinformatics, a luciferase assay, and RNA immunoprecipitation. Mechanistically, knockdown or exogenous expression of circRILPL1 in the primary myoblasts was performed to prove the functional significance of circRILPL1. We investigated the inhibitory effect of miR-145 on myoblast proliferation by targeting IGF1R to regulate the PI3K/AKT signaling pathway. A novel circRILPL1 was identified that could sponge miR-145 and is related to AKT activation. In addition, circRILPL1 was positively correlated with muscle proliferation and differentiation in vitro and could inhibit cell apoptosis. The newly identified circRILPL1 functions as a miR-145 sponge to regulate the IGF1R gene and rescue the inhibitory effect of miR-145 on the PI3K/AKT signaling pathway, thereby promoting myoblast growth.
Hsp90-stabilized MIF supports tumor progression via macrophage recruitment and angiogenesis in colorectal cancer
Authors: Klemke Luisa , De Oliveira Tiago , Witt Daria , Winkler Nadine , Bohnenberger Hanibal , Bucala Richard , Conradi Lena-Christin , Schulz-Heddergott Ramona 
Published: February 2021

AbstractMacrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity, but its expression is increased in some cancers via stabilization with HSP90-associated chaperones. Here, we show that MIF stabilization is tumor-specific in an acute colitis-associated colorectal cancer (CRC) mouse model, leading to tumor-specific functions and selective therapeutic vulnerabilities. Therefore, we demonstrate that a Mif deletion reduced CRC tumor growth. Further, we define a dual role for MIF in CRC tumor progression. Mif deletion protects mice from inflammation-associated tumor initiation, confirming the action of MIF on host inflammatory pathways; however, macrophage recruitment, neoangiogenesis, and proliferative responses are reduced in Mif-deficient tumors once the tumors are established. Thus, during neoplastic transformation, the function of MIF switches from a proinflammatory cytokine to an angiogenesis promoting factor within our experimental model. Mechanistically, Mif-containing tumor cells regulate angiogenic gene expression via a MIF/CD74/MAPK axis in vitro. Clinical correlation studies of CRC patients show the shortest overall survival for patients with high MIF levels in combination with CD74 expression. Pharmacological inhibition of HSP90 to reduce MIF levels decreased tumor growth in vivo, and selectively reduced the growth of organoids derived from murine and human tumors without affecting organoids derived from healthy epithelial cells. Therefore, novel, clinically relevant Hsp90 inhibitors provide therapeutic selectivity by interfering with tumorigenic MIF in tumor epithelial cells but not in normal cells. Furthermore, Mif-depleted colonic tumor organoids showed growth defects compared to wild-type organoids and were less susceptible toward HSP90 inhibitor treatment. Our data support that tumor-specific stabilization of MIF promotes CRC progression and allows MIF to become a potential and selective therapeutic target in CRC.
Gasdermin E deficiency attenuates acute kidney injury by inhibiting pyroptosis and inflammation
Authors: Xia Weiwei , Li Yuanyuan , Wu Mengying , Jin Qianqian , Wang Qian , Li Shuzhen , Huang Songming , Zhang Aihua , Zhang Yue , Jia Zhanjun 
Published: February 2021

AbstractPyroptosis, one kind of inflammatory regulated cell death, is involved in various inflammatory diseases, including acute kidney injury (AKI). Besides Gasdermin D (GSDMD), GSDME is a newly identified mediator of pyroptosis via the cleavage of caspase-3 generating pyroptotic GSDME-N. Here, we investigated the role of GSDME in renal cellular pyroptosis and AKI pathogenesis employing GSDME-deficient mice and human tubular epithelial cells (TECs) with the interventions of pharmacological and genetic approaches. After cisplatin treatment, GSDME-mediated pyroptosis was induced as shown by the characteristic pyroptotic morphology in TECs, upregulated GSDME-N expression and enhanced release of IL-1β and LDH, and decreased cell viability. Strikingly, silencing GSDME in mice attenuated acute kidney injury and inflammation. The pyroptotic role of GSDME was also verified in human TECs in vitro. Further investigation showed that inhibition of caspase-3 blocked GSDME-N cleavage and attenuated cisplatin-induced pyroptosis and kidney dysfunction. Moreover, deletion of GSDME also protected against kidney injury induced by ischemia-reperfusion. Taken together, the findings from current study demonstrated that caspase-3/GSDME-triggered pyroptosis and inflammation contributes to AKI, providing new insights into the understanding and treatment of this disease.
A fine balance between Prpf19 and Exoc7 in achieving degradation of aggregated protein and suppression of cell death in spinocerebellar ataxia type 3
Authors: Chen Zhefan Stephen , Huang Xiaoying , Talbot Kevin , Chan Ho Yin Edwin 
Published: February 2021

AbstractPolyglutamine (polyQ) diseases comprise Huntington’s disease and several subtypes of spinocerebellar ataxia, including spinocerebellar ataxia type 3 (SCA3). The genomic expansion of coding CAG trinucleotide sequence in disease genes leads to the production and accumulation of misfolded polyQ domain-containing disease proteins, which cause cellular dysfunction and neuronal death. As one of the principal cellular protein clearance pathways, the activity of the ubiquitin–proteasome system (UPS) is tightly regulated to ensure efficient clearance of damaged and toxic proteins. Emerging evidence demonstrates that UPS plays a crucial role in the pathogenesis of polyQ diseases. Ubiquitin (Ub) E3 ligases catalyze the transfer of a Ub tag to label proteins destined for proteasomal clearance. In this study, we identified an E3 ligase, pre-mRNA processing factor 19 (Prpf19/prp19), that modulates expanded ataxin-3 (ATXN3-polyQ), disease protein of SCA3, induced neurodegeneration in both mammalian and Drosophila disease models. We further showed that Prpf19/prp19 promotes poly-ubiquitination and degradation of mutant ATXN3-polyQ protein. Our data further demonstrated the nuclear localization of Prpf19/prp19 is essential for eliciting its modulatory function towards toxic ATXN3-polyQ protein. Intriguingly, we found that exocyst complex component 7 (Exoc7/exo70), a Prpf19/prp19 interacting partner, modulates expanded ATXN3-polyQ protein levels and toxicity in an opposite manner to Prpf19/prp19. Our data suggest that Exoc7/exo70 exerts its ATXN3-polyQ-modifying effect through regulating the E3 ligase function of Prpf19/prp19. In summary, this study allows us to better define the mechanistic role of Exoc7/exo70-regulated Prpf19/prp19-associated protein ubiquitination pathway in SCA3 pathogenesis.
AAV1.NT-3 gene therapy for X-linked Charcot–Marie–Tooth neuropathy type 1
Authors: Ozes Burcak , Myers Morgan , Moss Kyle , Mckinney Jennifer , Ridgley Alicia , Chen Lei , Bai Shasha , Abrams Charles K. , Freidin Mona M. , Mendell Jerry R. , Sahenk Zarife 
Published: February 2021

AbstractX-linked Charcot-Marie-Tooth neuropathy (CMTX) is caused by mutations in the gene encoding Gap Junction Protein Beta-1 (GJB1)/Connexin32 (Cx32) in Schwann cells. Neurotrophin-3 (NT-3) is an important autocrine factor supporting Schwann cell survival and differentiation and stimulating axon regeneration and myelination. Improvements in these parameters have been shown previously in a CMT1 model, TremblerJ mouse, with NT-3 gene transfer therapy. For this study, scAAV1.tMCK.NT-3 was delivered to the gastrocnemius muscle of 3-month-old Cx32 knockout (KO) mice. Measurable levels of NT-3 were found in the serum at 6-month post gene delivery. The outcome measures included functional, electrophysiological and histological assessments. At 9-months of age, NT-3 treated mice showed no functional decline with normalized compound muscle action potential amplitudes. Myelin thickness and nerve conduction velocity significantly improved compared with untreated cohort. A normalization toward age-matched wildtype histopathological parameters included increased number of Schmidt-Lanterman incisures, and muscle fiber diameter. Collectively, these findings suggest a translational application to CMTX1.