bluuebunny/crossref_metadata_2025_split huggingface dataset:
A microfluidic approach for synchronous and nondestructive study of the permeability of multiple oocytes
Authors: Chen Zhongrong , Memon Kashan , Cao Yunxia , Zhao Gang 
Published: July 2020

AbstractInvestigation of oocyte membrane permeability plays a crucial role in fertility preservation, reproductive medicine, and reproductive pharmacology. However, the commonly used methods have disadvantages such as high time consumption, low efficiency, and cumbersome data processing. In addition, the developmental potential of oocytes after measurement has not been fully validated in previous studies. Moreover, oocytes can only maintain their best status in vitro within a very limited time. To address these limitations, we developed a novel multichannel microfluidic chip with newly designed micropillars that provide feasible and repeatable oocyte capture. The osmotic responses of three oocytes at different or the same cryoprotectant (CPA) concentrations were measured simultaneously, which greatly improved the measurement efficiency. Importantly, the CPA concentration dependence of mouse oocyte membrane permeability was found. Moreover, a neural network algorithm was employed to improve the efficiency and accuracy of data processing. Furthermore, analysis of fertilization and embryo transfer after perfusion indicated that the microfluidic approach does not damage the developmental potential of oocytes. In brief, we report a new method based on a multichannel microfluidic chip that enables synchronous and nondestructive measurement of the permeability of multiple oocytes.
Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study
Authors: Thygesen Johan H. , Presman Amelia , Harju-Seppänen Jasmine , Irizar Haritz , Jones Rebecca , Kuchenbaecker Karoline , Lin Kuang , Alizadeh Behrooz Z. , Austin-Zimmerman Isabelle , Bartels-Velthuis Agna , Bhat Anjali , Bruggeman Richard , Cahn Wiepke , Calafato Stella , Crespo-Facorro Benedicto , de Haan Liewe , de Zwarte Sonja M. C. , Di Forti Marta , Díez-Revuelta Álvaro , Hall Jeremy , Hall Mei-Hua , Iyegbe Conrad , Jablensky Assen , Kahn Rene , Kalaydjieva Luba , Kravariti Eugenia , Lawrie Stephen , Luykx Jurjen J. , Mata Igancio , McDonald Colm , McIntosh Andrew M. , McQuillin Andrew , Muir Rebecca , Ophoff Roel , Picchioni Marco , Prata Diana P. , Ranlund Siri , Rujescu Dan , Rutten Bart P. F. , Schulze Katja , Shaikh Madiha , Schirmbeck Frederike , Simons Claudia J. P. , Toulopoulou Timothea , van Amelsvoort Therese , van Haren Neeltje , van Os Jim , van Winkel Ruud , Vassos Evangelos , Walshe Muriel , Weisbrod Matthias , Zartaloudi Eirini , Bell Vaughan , Powell John , Lewis Cathryn M. , Murray Robin M. , Bramon Elvira 
Published: July 2020

AbstractThe burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.
Suppression of G6PD induces the expression and bisecting GlcNAc-branched N-glycosylation of E-Cadherin to block epithelial-mesenchymal transition and lymphatic metastasis
Authors: Wang Yifei , Li Qingxiang , Niu Lixuan , Xu Le , Guo Yuxing , Wang Lin , Guo Chuanbin 
Published: July 2020

Abstract
Background
As the rate-limit enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PD) plays important roles in tumour progression, but the exact mechanism through which G6PD controls cancer metastasis remains unclear.

Methods
G6PD expression in resected oral squamous cell carcinoma (OSCC) samples was analysed by immunohistochemistry. The effects and mechanism of G6PD suppression on OSCC cell lines were measured by transwell assay, wound healing assay, western and lectin blot, mass spectrometer analysis, ChIP-PCR, and luciferase reporter assay. BALB/c-nude mice were used to establish orthotopic xenograft model.

Results
G6PD expression in the tumours of 105 OSCC patients was associated with lymphatic metastasis and prognosis. In vitro cellular study suggested that G6PD suppression impaired cell migration, invasion, and epithelial-mesenchymal transition. Furtherly, G6PD knockdown activated the JNK pathway, which then blocked the AKT/GSK-3β/Snail axis to induce E-Cadherin expression and transcriptionally regulated MGAT3 expression to promote bisecting GlcNAc-branched N-glycosylation of E-Cadherin. An orthotopic xenograft model further confirmed that dehydroepiandrosterone reduced lymphatic metastatic rate of OSCC, which was partially reversed by JNK inhibition.

Conclusions
Suppression of G6PD promoted the expression and bisecting GlcNAc-branched N-glycosylation of E-Cadherin via activating the JNK pathway, which thus acted on OSCC metastasis.
SMAC mimetics induce autophagy-dependent apoptosis of HIV-1-infected macrophages
Authors: Campbell Grant R. , To Rachel K. , Zhang Gang , Spector Stephen A. 
Published: July 2020

AbstractHuman immunodeficiency type 1 (HIV)-infected macrophages (HIV-Mφ) are a reservoir for latent HIV infection and a barrier to HIV eradication. In contrast to CD4+ T cells, HIV-Mφ are resistant to the cytopathic effects of acute HIV infection and have increased expression of cell survival factors, including X-linked inhibitor of apoptosis (XIAP), baculoviral IAP repeat containing (BIRC) 2/cIAP1, beclin-1, BCL2, BCL-xl, triggering receptor expressed on myeloid cells 1, mitofusin (MFN) 1, and MFN2. DIABLO/SMAC mimetics are therapeutic agents that affect cancer cell survival and induce cell death. We found that DIABLO/SMAC mimetics (LCL-161, AT-406 (also known as SM-406 or Debio 1143), and birinapant) selectively kill HIV-Mφ without increasing bystander cell death. DIABLO/SMAC mimetic treatment of HIV-Mφ-induced XIAP and BIRC2 degradation, leading to the induction of autophagy and the formation of a death-inducing signaling complex on phagophore membranes that includes both pro-apoptotic or necroptotic (FADD, receptor-interacting protein kinase (RIPK) 1, RIPK3, caspase 8, and MLKL) and autophagy (ATG5, ATG7, and SQSTM1) proteins. Genetic or pharmacologic inhibition of early stages of autophagy, but not late stages of autophagy, ablated this interaction and inhibited apoptosis. Furthermore, DIABLO/SMAC mimetic-mediated apoptosis of HIV-Mφ is dependent upon tumor necrosis factor signaling. Our findings thus demonstrate that DIABLO/SMAC mimetics selectively induce autophagy-dependent apoptosis in HIV-Mφ.
Ciclopirox activates PERK-dependent endoplasmic reticulum stress to drive cell death in colorectal cancer
Authors: Qi Jianjun , Zhou Ningning , Li Liyi , Mo Shouyong , Zhou Yidan , Deng Yao , Chen Ting , Shan Changliang , Chen Qin , Lu Bin 
Published: July 2020

AbstractCiclopirox (CPX) modulates multiple cellular pathways involved in the growth of a variety of tumor cell types. However, the effects of CPX on colorectal cancer (CRC) and the underlying mechanisms for its antitumor activity remain unclear. Herein, we report that CPX exhibited strong antitumorigenic properties in CRC by inducing cell cycle arrest, repressing cell migration, and invasion by affecting N-cadherin, Snail, E-cadherin, MMP-2, and MMP-9 expression, and disruption of cellular bioenergetics contributed to CPX-associated inhibition of cell growth, migration, and invasion. Interestingly, CPX-induced reactive oxygen species (ROS) production and impaired mitochondrial respiration, whereas the capacity of glycolysis was increased. CPX (20 mg/kg, intraperitoneally) substantially inhibited CRC xenograft growth in vivo. Mechanistic studies revealed that the antitumor activity of CPX relies on apoptosis induced by ROS-mediated endoplasmic reticulum (ER) stress in both 5-FU-sensitive and -resistant CRC cells. Our data reveal a novel mechanism for CPX through the disruption of cellular bioenergetics and activating protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent ER stress to drive cell death and overcome drug resistance in CRC, indicating that CPX could potentially be a novel chemotherapeutic for the treatment of CRC.
Stabilization of ADAM9 by N-α-acetyltransferase 10 protein contributes to promoting progression of androgen-independent prostate cancer
Authors: Lin Yung-Wei , Wen Yu-Ching , Chu Chih-Ying , Tung Min-Che , Yang Yi-Chieh , Hua Kuo-Tai , Pan Ke-Fan , Hsiao Michael , Lee Wei-Jiunn , Chien Ming-Hsien 
Published: July 2020

AbstractN-α-Acetyltransferase 10 protein (Naa10p) was reported to be an oncoprotein in androgen-dependent prostate cancer (PCa; ADPC) through binding and increasing transcriptional activity of the androgen receptor (AR). PCa usually progresses from an androgen-dependent to an androgen-independent stage, leading to an increase in the metastatic potential and an incurable malignancy. At present, the role of Naa10p in androgen-independent prostate cancer (AIPC) remains unclear. In this study, in silico and immunohistochemistry analyses showed that Naa10 transcripts or the Naa10p protein were more highly expressed in primary and metastatic PCa cancer tissues compared to adjacent normal tissues and non-metastatic cancer tissues, respectively. Knockdown and overexpression of Naa10p in AIPC cells (DU145 and PC-3M), respectively, led to decreased and increased cell clonogenic and invasive abilities in vitro as well as tumor growth and metastasis in AIPC xenografts. From the protease array screening, we identified a disintegrin and metalloprotease 9 (ADAM9) as a potential target of Naa10p, which was responsible for the Naa10p-induced invasion of AIPC cells. Naa10p can form a complex with ADAM9 to maintain ADAM9 protein stability and promote AIPC’s invasive ability which were independent of its acetyltransferase activity. In contrast to the Naa10p-ADAM9 axis, ADAM9 exerted positive feedback regulation on Naa10p to modulate progression of AIPC in vitro and in vivo. Taken together, for the first time, our results reveal a novel cross-talk between Naa10p and ADAM9 in regulating the progression of AIPC. Disruption of Naa10p–ADAM9 interactions may be a potential intervention for AIPC therapy.
High-dimensional single-cell analysis delineates radiofrequency ablation induced immune microenvironmental remodeling in pancreatic cancer
Authors: Fei Qinglin , Pan Yu , Lin Wenji , Zhou Yuanyuan , Yu Xingxing , Hou Zelin , Yu Xunbin , Lin Xianchao , Lin Ronggui , Lu Fengchun , Guan Hongdan , Huang Heguang 
Published: July 2020

AbstractRadiofrequency ablation (RFA) is an effective local therapy approach for treating solitary tumor of many types of malignancy. The impact of RFA on the tumor immune microenvironment on distant tumors after RFA treatment is still unclear. In this study, by using syngeneic tumor models and single-cell RNA and T-cell receptor sequencing, we have investigated the alterations of tumor-infiltrating immune cells in distant non-RFA tumors. Single-cell RNA sequencing identified six distinct lymphoid clusters, five distinct monocyte/macrophage clusters, three dendritic cells clusters, and one cluster of neutrophils. We found that RFA treatment reduced the proportions of immunosuppressive cells including regulatory T cells, tumor-associated macrophages and tumor-associated neutrophils, whereas increased the percentages of functional T cells in distant non-RFA tumors. Moreover, RFA treatment also altered gene expressions in single-cell level in each cell cluster. By using pseudo-time analysis, we have described the biological processes of tumor-infiltrating CD8+ T cells and monocytes/macrophages based on the transcriptional profiles. In addition, the immune checkpoints including PD-1 and LAG3 were upregulated in the T cells in distant non-RFA tumors after RFA treatment. In conclusion, our data indicate that RFA treatment induced remodeling of tumor immune microenvironment in distant non-RFA tumors in pancreatic cancer mouse model and suggest that combining RFA with immune checkpoint inhibitors may be an effective treatment approach.
MiR-3622a-3p acts as a tumor suppressor in colorectal cancer by reducing stemness features and EMT through targeting spalt-like transcription factor 4
Authors: Chang Shuchen , Sun Guangli , Zhang Dan , Li Qing , Qian Haihua 
Published: July 2020

AbstractMicroRNAs are a class of small non-coding RNAs which act as oncogenes or tumor suppressors through targeting specific mRNAs. Colorectal cancer (CRC) is one of the most common malignancies worldwide. MiR-3622a-3p is found to be decreased in colorectal cancer (CRC) by analyzing data from TCGA database and there are few reports about the role of miR-3622a-3p in cancers. Our research aimed to explore the effects of miR-3622a-3p on CRC. MiR-3622a-3p was found to be down-regulated in CRC tissues and cells by qRT-PCR. The effect of miR-3622a-3p on proliferation, apoptosis, cell cycle, migration and invasion of CRC cells were investigated by a serious of biological function assays and the results revealed that miR-3622a-3p could inhibit the malignant biological properties of CRC. We performed dual luciferase assay, RNA immunoprecipitation (RIP) assay and pull-down assay to confirm the interaction between miR-3622a-3p and spalt-like transcription factor 4 (SALL4). Western blot was carried out to determine the effects of miR-3622a-3p and SALL4 on stemness features and EMT. We found that miR-3622a-3p suppressed stemness features and EMT of CRC cells by SALL4 mRNA degradation. MiR-3622a-3p could inhibit CRC cell proliferation and metastasis in vivo with tumor xenograft model and in vivo metastasis model. The CRC organoid model was constructed with fresh CRC tissues and the growth of organoids was suppressed by miR-3622a-3p. Taken together, the results of our study indicate miR-3622a-3p exerts antioncogenic role in CRC by downregulation of SALL4. The research on miR-3622a-3p might provide a new insight into treatment of CRC.
LIF is essential for ISC function and protects against radiation-induced gastrointestinal syndrome
Authors: Wang Huaying , Wang Jianming , Zhao Yuhan , Zhang Xiao , Liu Juan , Zhang Cen , Haffty Bruce , Verzi Michael , Zhang Lanjing , Gao Nan , Feng Zhaohui , Hu Wenwei 
Published: July 2020

AbstractLeukemia inhibitory factor (LIF) is a cytokine essential for maintaining pluripotency of mouse embryonic stem cells. However, its role in adult intestinal stem cells (ISCs) is unclear. The adult intestinal epithelium has a high self-renewal rate driven by ISCs in crypts. Here, we find that LIF is present in the ISC niche in crypts and critical for the function of ISCs in maintaining the intestinal epithelial homeostasis and regeneration. Mechanistically, LIF maintains β-catenin activity through the AKT/GSK3β signaling to regulate ISC functions. LIF deficiency in mice impairs the renewal of the intestinal epithelium under the physiological condition. Further, LIF deficiency in mice impairs the regeneration of intestinal epithelium in response to radiation and shortens the lifespan of mice after high doses of radiation due to gastrointestinal (GI) syndrome, which can be rescued by administering recombinant LIF (rLIF). Importantly, LIF exhibits a radioprotective role in wild-type (WT) mice by protecting mice from lethal radiation-induced GI syndrome; administering rLIF promotes intestinal epithelial regeneration and prolongs survival in WT mice after radiation. These results reveal a previously unidentified and a crucial role of LIF in ensuring ISC function, promoting regeneration of the intestinal epithelium in response to radiation and protecting against radiation-induced GI syndrome.
Association of lncRNA SH3PXD2A-AS1 with preeclampsia and its function in invasion and migration of placental trophoblast cells
Authors: Chen Qian , Jiang Sijia , Liu Haihua , Gao Yue , Yang Xiaoxue , Ren Zhonglu , Gao Yunfei , Xiao Lu , Hu Haoyue , Yu Yanhong , Yang Xinping , Zhong Mei 
Published: July 2020

AbstractAccumulating evidence suggests that the pathogenesis of preeclampsia involves poor placentation caused by insufficient trophoblast invasion and impaired uterine spiral artery remodeling, yet the underlying molecular mechanism remains unclear. We carried out transcriptome profiling on placentae from preeclamptic patients and normal subjects, and identified about four hundred long non-coding RNAs differentially expressed in placentae of patients with early-onset severe preeclampsia. Here, we report our identification of lncRNA SH3PXD2A-AS1 as a potential causal factor for this disease and its downstream pathways involved in placentation. We found that expression level of SH3PXD2A-AS1 in the placentae is positively correlated with clinical severity of the patients. We demonstrated that SH3PXD2A-AS1 inhibited invasion and migration through recruiting CCCTC-binding factor (CTCF) to the promoters of SH3PXD2A and CCR7 to inhibit their transcription. Therefore, we conclude that the upregulation of lncRNA SH3PXD2A-AS1 may contribute to the pathogenesis of preeclampsia through prohibiting trophoblast invasion during placentation.
Bioactive DNA from extracellular vesicles and particles
Authors: Malkin Ethan Z. , Bratman Scott V. 
Published: July 2020

AbstractExtracellular vesicles (EVs) and particles (EPs) have recently emerged as active carriers of molecular biomarkers and mediators of intercellular communication. While most investigations have focused exclusively on the protein, lipid and RNA constituents of these extracellular entities, EV/EP DNA remains poorly understood, despite DNA being found in association with virtually all EV/EP populations. The functional potential of EV/EP DNA has been proposed in a number of pathological states, including malignancies and autoimmune diseases. Moreover, the effectiveness of cell-free DNA as the biomarker of choice in emerging liquid biopsy applications highlights the role that EV/EP DNA may play as a novel disease biomarker. In this review, we provide a comprehensive overview of EV/EP DNA studies conducted to date, with a particular focus on the roles of EV/EP DNA as a functional mediator and molecular biomarker in various pathologic states. We also review what is currently known about the origins, structure, localisation and distribution of EV/EP DNA, highlighting current controversies as well as opportunities for future investigation.
Targeting Rad51 as a strategy for the treatment of melanoma cells resistant to MAPK pathway inhibition
Authors: Makino Elena , Fröhlich Lisa Marie , Sinnberg Tobias , Kosnopfel Corinna , Sauer Birgit , Garbe Claus , Schittek Birgit 
Published: July 2020

AbstractRad51 is an essential factor of the homologous recombination DNA repair pathway and therefore plays an important role in maintaining genomic stability. We show that RAD51 and other homologous recombination repair genes are overexpressed in metastatic melanoma cell lines and in melanoma patient samples, which correlates with reduced survival of melanoma patients. In addition, Rad51 expression in melanoma cells was regulated on a transcriptional level by the MAPK signaling pathway with Elk1 as the main downstream transcriptional effector. Most strikingly, melanoma cells which developed resistance towards MAPK inhibitors could be efficiently targeted by Rad51 inhibitors similar to their sensitive counterparts, leading to DNA damage, G2/M arrest and apoptosis. Furthermore, the treatment of MAPK inhibitor resistant cells with Rad51 inhibitors enhances the susceptibility of these cells for MAPK inhibitor treatment in vitro and in vivo. These data indicate that Rad51 plays a critical role in the survival of metastatic melanoma cells and is a promising target for the therapy of melanoma irrespective of its MAPK inhibitor resistance status.
TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing
Authors: Schöpp Theresa , Zoch Ansgar , Berrens Rebecca V. , Auchynnikava Tania , Kabayama Yuka , Vasiliauskaitė Lina , Rappsilber Juri , Allshire Robin C. , O’Carroll Dónal 
Published: July 2020

AbstractThe PIWI protein MIWI2 and its associated PIWI-interacting RNAs (piRNAs) instruct DNA methylation of young active transposable elements (TEs) in the male germline. piRNAs are proposed to recruit MIWI2 to the transcriptionally active TE loci by base pairing to nascent transcripts, however the downstream mechanisms and effector proteins utilized by MIWI2 in directing de novo TE methylation remain incompletely understood. Here, we show that MIWI2 associates with TEX15 in foetal gonocytes. TEX15 is predominantly a nuclear protein that is not required for piRNA biogenesis but is essential for piRNA-directed TE de novo methylation and silencing. In summary, TEX15 is an essential executor of mammalian piRNA-directed DNA methylation.
Tracing animal genomic evolution with the chromosomal-level assembly of the freshwater sponge Ephydatia muelleri
Authors: Kenny Nathan J. , Francis Warren R. , Rivera-Vicéns Ramón E. , Juravel Ksenia , de Mendoza Alex , Díez-Vives Cristina , Lister Ryan , Bezares-Calderón Luis A. , Grombacher Lauren , Roller Maša , Barlow Lael D. , Camilli Sara , Ryan Joseph F. , Wörheide Gert , Hill April L. , Riesgo Ana , Leys Sally P. 
Published: July 2020

AbstractThe genomes of non-bilaterian metazoans are key to understanding the molecular basis of early animal evolution. However, a full comprehension of how animal-specific traits, such as nervous systems, arose is hindered by the scarcity and fragmented nature of genomes from key taxa, such as Porifera. Ephydatia muelleri is a freshwater sponge found across the northern hemisphere. Here, we present its 326 Mb genome, assembled to high contiguity (N50: 9.88 Mb) with 23 chromosomes on 24 scaffolds. Our analyses reveal a metazoan-typical genome architecture, with highly shared synteny across Metazoa, and suggest that adaptation to the extreme temperatures and conditions found in freshwater often involves gene duplication. The pancontinental distribution and ready laboratory culture of E. muelleri make this a highly practical model system which, with RNAseq, DNA methylation and bacterial amplicon data spanning its development and range, allows exploration of genomic changes both within sponges and in early animal evolution.