PReD-Bench/PRed-Bench huggingface dataset:
MiR-338-5p suppresses proliferation, migration, invasion, and promote apoptosis of glioblastoma cells by directly targeting EFEMP1
Authors: Hongyang Zhao
Nanxiang Xiong
Xiaobing Jiang
Deqiang Lei
Fangcheng Zhang
Dongxiao Yao
Journal: Biomedicine & Pharmacotherapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: EFEMP1; Glioblastoma; MiR-338-5p; Progression.
Affiliations: Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. Electronic address: ., Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.

Abstract:  Objective: We aimed to investigate the effect of miR-338-5p on proliferation, migration and invasion of glioblastoma (GBM) cells by regulating EFEMP1. Methods: The expression of miR-338-5p and EFEMP1 was measured by qRT-PCR and western blot. Transfection was conducted to regulate the expression of miR-338-5p and EFEMP1 in U87 cell lines. Cell proliferation, apoptosis, migration and invasion were evaluated using CCK-8 assay, flow cytometry and Transwell assay respectively. Dual luciferase reporter assay was performed to verify whether miR-338-5p directly targeted EFEMP1. Results: MiR-338-5p was significantly down-regulated in human GBM tumor tissues and cells while EFEMP1 was strongly upregulated (P&lt;0.05). Upregulated miR-338-5p was able to suppress cell proliferation, migration, invasion, and promote cell apoptosis in GBM cells (P&lt;0.05). Dual luciferase reporter gene assay determined that miR-338-5p directly targeted EFEMP1 (P&lt;0.05). Conclusions: MiR-338-5p suppressed proliferation, migration and invasion of GBM cells through inhibiting EFEMP1. 

Retracted: No

PubPeer comments:
 Figure 2C. * Blue boxes: The  Control and  miR-NC panels appear to look identical. Also, some dots fall outside of the axes. ![file] , 
 Figure 3. Some of the panels appear to show repetitive elements within or between panels, albeit sometimes in mirror image. Boxes of the same color highlight parts that look remarkably similar. ![file] , 
 Figure 5C. Some of the panels appear to show repetitive elements within or between panels, albeit sometimes rotated or at a different position. Boxes of the same color highlight parts that look remarkably similar. ![file] , 
 Figure 6 has some issues too (within panels as well as with respect to Figure 3) but I will leave these as an exercise for the reader. ,
Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury
Authors: David S Latchman
Tiziano M Scarabelli
Kevin M Laurence
Anastasis Stephanou
Christopher J Carroll
Richard A Knight
Surinder Soond
Paul A Townsend
Lauren Valentim
Journal: Journal of molecular and cellular cardiology (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Autophagy; Ischaemia/reperfusion; Cardiomyocytes; Beclin1; RNAi
Affiliations: Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.

Abstract:  Autophagy is known to be a feature of cardiomyopathies and chronic ischaemia. Here we demonstrate that autophagy is also induced by a single cycle of ischaemia/reperfusion (I/R in neonatal and adult rat cardiac myocytes). Consistent with the critical role for Beclin1 in autophagocytosis, reduction of Beclin1 expression in cardiac myocytes by RNAi reduces I/R-induced autophagy and this is associated with enhanced cell survival. Autophagy is also reduced by urocortin, an endogenous cardiac peptide which we have previously shown to reduce other forms of myocyte cell death induced by I/R. The inhibition of autophagy by urocortin is mediated in part by inhibition of Beclin1 expression, an effect which is mediated by activation of the PI3 kinase/Akt pathway but which does not involve activation of p42/p44 MAPK. 

Retracted: No

PubPeer comments:
 Fig. 3A looks like having some splicing. Any explanation? ![file] , 
 I apologize for my lax review of student lab results more than a decade ago. I will communicate with the magazine to make up the experiment or withdraw the manuscript. Thank you very much! , 
 #2 Thank you for responding to my comment. There are 3 other papers that you co-authored that you may want to take a look as well: https: pubpeer.com publications 57BFC283DA0351135B3DDDEAB1FCFF https: pubpeer.com publications 9DE93690DCB06BABB7216C760E9D19 https: pubpeer.com publications FA510E0DEEEEBAA91CA7D2E4F40DA3 ,
ADAM12-L confers acquired 5-fluorouracil resistance in breast cancer cells
Authors: Xuedong Wang
Xinhui Wang
Daoping Zhou
Zhimin He
Juan Gu
Yueping Wang
Soldano Ferrone
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: 5-FU; breast cancer; chemoresistance; ADAM12; recurrence
Affiliations: Department of Medical Laboratory Science, The Fifth People's Hospital of Wuxi, The Medical School of Jiangnan University Wuxi, Wuxi, Jiangsu, 214005, China., Department of Pathology, The Fifth People's Hospital of Wuxi, Nanjing Medical University, Wuxi, Jiangsu, 214005, China., Department of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA., Department of Biology, College of Arts & Science, Massachusetts University, Boston, MA, 02125, USA., Department of Medical Laboratory Science, The Fifth People's Hospital of Wuxi, The Medical School of Jiangnan University Wuxi, Wuxi, Jiangsu, 214005, China. ., Department of Pathology, The Fifth People's Hospital of Wuxi, Nanjing Medical University, Wuxi, Jiangsu, 214005, China. ., Department of Oncology, The Second People's Hospital of Anhui Province, Anhui Medical University, Hefei, Anhui, 230041, China., Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou, Guangdong, 510095, China.

Abstract:  5-FU-based combinatory chemotherapeutic regimens have been routinely used for many years for the treatment of breast cancer patients. Recurrence and chemotherapeutic drug resistance are two of the most prominent factors that underpin the high mortality rates associated with most breast cancers (BC). Increasing evidence indicates that overexpression of ADAMs could correlate with cancer progression. However, the role of ADAMs in the chemoresistance of cancer cells has rarely been reported. In this study, we observed that 5-FU induces expression of the ADAM12 isoform ADAM12-L but not ADAM12-S in BC cells and in recurrent BC tissues. The overexpression of ADAM12-L in BC cells following 5-FU treatment results in the acquisition of resistance to 5-FU. ADAM12-L overexoression also resulted in increased levels of p-Akt but not p-ERK. These alterations enhanced BC cell growth and invasive abilities. Conversely, ADAM12 knockdown attenuated the levels of p-Akt and restored 5-FU sensitivity in 5-FU-resistant BC cells. ADAM12 knockdown also reduced BC cell survival and invasive abilities. These findings suggest that ADAM12-L mediates chemoresistance to 5-FU and 5-FU-induced recurrence of BC by enhancing PI3K/Akt signaling. The results of this study suggest that specific ADAM12-L inhibition could optimize 5-FU-based chemotherapy of BC, thereby preventing BC recurrence in patients. 

Retracted: No

PubPeer comments:
 The actin band in Figure 3A appears to be the same after flipping horizontally and changing the contrast. Itu2019s difficult to understand how this could happen by chance. *** ![file] ,
Long non-coding RNA p53 upregulated regulator of p53 levels (PURPL) promotes the development of gastric cancer
Authors: Zhen Feng
Zhonghua Cheng
Fenghua Liu
Jing Hong
Shuo Gu
Nan Tang
Journal: Bioengineered (2022)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Gastric cancer; PURPL; ZBTB7A; miR-137; progression
Affiliations: Department of Gastroenterology, The Central Hospital of Xuhui District, Xuhui Hospital, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China

Abstract:  Gastric cancer (GC), one of the most prevalent malignancies across the world, has an increasing incidence rate. Long non-coding RNA (lncRNA) PURPL (also referred to as LINC01021) has been demonstrated to influence malignant GC behaviors and partake in other cancers. Notwithstanding, reports pertaining to the underlying mechanism of PURPL in GC haven't been rarely seen. Presently, in-vivo and ex-vivo experiments were implemented to examine the PURPL-miR-137-ZBTB7A-PI3K-AKT-NF-κB regulatory axis in GC. Our statistics revealed that PURPL presented a high expression in GC tissues and cell lines. PURPL overexpression remarkably exacerbated colony formation, migration, and invasion and repressed apoptosis in GC cells (AGS and MNK-45). In-vivo experiments also corroborated that cell growth was boosted by PURPL up-regulation. Mechanistic investigations verified that PURPL interacted with miR-137 and lowered its profile in GC cell lines. miR-137 overexpression or ZBTB7A knockdown upended the oncogenic function mediated by PURPL. PURPL initiated the PI3K/AKT/NF-κB pathway. PI3K and NF-κB inhibition impaired the promoting impact on GC cells elicited by PURPL overexpression and contributed to PURPL down-regulation. These findings disclosed that PURPL serves as an oncogene in the context of GC via miR-137-ZBTB7A-PI3K-AKT-NF-κB axis modulation. 

Retracted: No

PubPeer comments:
 Two of the qRT-PCR primers listed in Table 1 appear to be incorrect. Furthermore, nine of the references in this article are citations of other Bioengineered papers. Even more interestingly, they are limited to two single issues (2020, Dec (5 papers) and 2021, Dec (4 papers). Clearly a form of driving up the journal impact factor. There is no funding associated with this study, common for the many papermill papers we have identified previously. ![file] , 
 I don t expect any reply from the papermill, but I can add another question: For the xenograft experiment, 20 mice were used. They were divided into two groups, 10 in each. In the presentation of the results from the xenograft experiment (Figure 3), only tumors from 12 mice are shown. What happened to the additional 8 mice? ![file] ,
Isolated copper–tin atomic interfaces tuning electrocatalytic CO2 conversion
Authors: Xin Liu
Kaixue Wang
Sesi Li
Xin Tan
Simon P Ringer
Chuan Zhao
Julie M Cairney
Sean C Smith
Jiangtao Qu
Wenhao Ren
Jiantao Li
Journal: Nature Communications (2021)
Discipline: Multidisciplinary
Keywords: heterogeneous catalysis; interface structure; single atom; surface science; Cu-Sn surface alloys
Affiliations: School of Chemistry, University of New South Wales, Sydney, NSW, Australia., Integrated Materials Design Laboratory, Department of Applied Mathematics, Research School of Physics, The Australian National University Canberra, Canberra, ACT, Australia., Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, Sydney, NSW, Australia., School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, China., State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, China., School of Chemistry, University of New South Wales, Sydney, NSW, Australia. .

Abstract:  Direct experimental observations of the interface structure can provide vital insights into heterogeneous catalysis. Examples of interface design based on single atom and surface science are, however, extremely rare. Here, we report Cu-Sn single-atom surface alloys, where isolated Sn sites with high surface densities (up to 8%) are anchored on the Cu host, for efficient electrocatalytic CO2 reduction. The unique geometric and electronic structure of the Cu-Sn surface alloys (Cu97Sn3 and Cu99Sn1) enables distinct catalytic selectivity from pure Cu100 and Cu70Sn30 bulk alloy. The Cu97Sn3 catalyst achieves a CO Faradaic efficiency of 98% at a tiny overpotential of 30 mV in an alkaline flow cell, where a high CO current density of 100 mA cm-2 is obtained at an overpotential of 340 mV. Density functional theory simulation reveals that it is not only the elemental composition that dictates the electrocatalytic reactivity of Cu-Sn alloys; the local coordination environment of atomically dispersed, isolated Cu-Sn bonding plays the most critical role. 

Retracted: No

PubPeer comments:
 The CV curves in supplementary Figure 13 (d,e,f) is really weird. As we can see below, zigzag patterns with unexpected similarity periodically appear. In fact, the capacitive current in this Faradaic region won t produce such strong vibration as no perturbation from gas production. How to explain this odd caseuff1f ![file] , 
 #1 I agree the wiggles are very surprising. The reproducibility is also striking. In the figures below I compare the up- and down-going traces by overlapping the figure with a 180 degree rotated version of itself. Strikingly, the same noise is observed. Red curves perfectly duplicates (top and bottom!) after 180 degree rotation, including the odd noise burst-flat sequence. Click to animate. ![file] Green curves nearly duplicate (top and bottom!) after 180 degree rotation. Click to animate. ![file] Same for others, just a different shift needed. Can the authors clarify what is happening here? ,
Near-infrared quantum dots for HER2 localization and imaging of cancer cells
Authors: Shohei Taniguchi
Mark Green
Shi Yu Yang
Sarwat B Rizvi
Sepideh Rouhi
Alexander M Seifalian
Mo Keshtgar
Journal: International Journal of Nanomedicine (2014)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: HER2 localization; anti-HER2 antibody; cancer; in vitro imaging; nanotechnology
Affiliations: UCL Centre for Nanotechnology and Regenerative Medicine, University College London, London, UK., Department of Physics, King's College London, London, UK., UCL Centre for Nanotechnology and Regenerative Medicine, University College London, London, UK ; Royal Free London NHS Foundation Trust Hospital, London, UK.

Abstract:  Background: Quantum dots are fluorescent nanoparticles with unique photophysical properties that allow them to be used as diagnostic, therapeutic, and theranostic agents, particularly in medical and surgical oncology. Near-infrared-emitting quantum dots can be visualized in deep tissues because the biological window is transparent to these wavelengths. Their small sizes and free surface reactive groups that can be conjugated to biomolecules make them ideal probes for in vivo cancer localization, targeted chemotherapy, and image-guided cancer surgery. The human epidermal growth factor receptor 2 gene (HER2/neu) is overexpressed in 25%-30% of breast cancers. The current methods of detection for HER2 status, including immunohistochemistry and fluorescence in situ hybridization, are used ex vivo and cannot be used in vivo. In this paper, we demonstrate the application of near-infrared-emitting quantum dots for HER2 localization in fixed and live cancer cells as a first step prior to their in vivo application. Methods: Near-infrared-emitting quantum dots were characterized and their in vitro toxicity was established using three cancer cell lines, ie, HepG2, SK-BR-3 (HER2-overexpressing), and MCF7 (HER2-underexpressing). Mouse antihuman anti-HER2 monoclonal antibody was conjugated to the near-infrared-emitting quantum dots. Results: In vitro toxicity studies showed biocompatibility of SK-BR-3 and MCF7 cell lines with near-infrared-emitting quantum dots at a concentration of 60 μg/mL after one hour and 24 hours of exposure. Near-infrared-emitting quantum dot antiHER2-antibody bioconjugates successfully localized HER2 receptors on SK-BR-3 cells. Conclusion: Near-infrared-emitting quantum dot bioconjugates can be used for rapid localization of HER2 receptors and can potentially be used for targeted therapy as well as image-guided surgery. 

Retracted: No

PubPeer comments:
 image duplications ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. , 
 #1 I agree. Some images seem to have repeated features within the images. *** Figure 2 ![file] *** Figure 7 ![file] *** Figure 8 ![file] ,
MicroRNA-539 inhibits the progression of Wilms’ Tumor through downregulation of JAG1 and Notch1/3
Authors: Yingchun Zhao
Yongjiao Wang
Hailong Su
Jingjing Song
Xuebo Wang
Juan Meng
Journal: Cancer Biomarkers (2019)
Discipline: CLINICAL MEDICINE
Keywords: JAG1; Notch 1; Notch 3; Wilms Tumor; miR-539.
Affiliations: Department of Pediatric Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China., Department of Clinical Laboratory, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China., Department of Clinical Laboratory, People's Hospital of Rizhao, Rizhao, Shandong, China., Department of Internal Medicine, Community Health Service Center, Zao Yuan Street Office of Zhangqiu District, Jinan, Shandong, China., Department of Pediatrics, The People's Hospital of Zhangqiu Area, Jinan, Shandong, China., Department of Blood Transfusion, Yankuang New Journey General Hospital, Zoucheng, Shandong, China.

Abstract:  Background: Previous studies demonstrated that miR-539 play an important role in the carcinogenesis of some cancers. The aim of the present study was to determine the role of miR-539 in the pathogenesis of Wilms' Tumor (WT). Methods: The expression level of miR-539 was measured by qRT-PCR in 42 WT tissues and SK-NEP-1 cell line. Protein expression of genes (E-cadherin, N-cadherin, Vimentin, Notch 1, Notch 3 and JAG1) was assessed by Western blot. The function of miR-539 was investigated in SK-NEP-1 cells by MTT and Transwell assays. The relationship between miR-539 and JAG1 was verified by a dual luciferase assay in SK-NEP-1 cells. Results: The expression level of miR-539 was significantly decreased in WT tissues. Downregulation of miR-539 was closely related to NWTS-5 stage, lymph node metastasis and histological type of WT patients. Furthermore, low miR-539 expression was associated with a shorter overall survival rate in WT patients. In vitro, overexpression of miR-539 suppressed proliferation, migration and invasion of SK-NEP-1 cells. In addition, JAG1 was a direct target of miR-539. MiR-539 inhibited the development of WT by inhibiting JAG1-Notch1/3 expressing and blocking EMT. Conclusion: MiR-539 inhibited the progression of WT through downregulation of JAG1 and Notch1/3. 

Retracted: No

PubPeer comments:
 The SK-NEP-1 cell line was originally incorrectly characterized as a Wilms tumor. It is in fact an Ewing Sarcoma cell line as defined by the EWSR1-FLI1 translocation that is reliably present in the cells. Therefore, the data in this study do not support the conclusions regarding Wilms tumor biology. , 
 Fig 4.  (E, F) The cell migration and invasion in SK-NEP-1 cells with JAG1 vector and miR-539 was measured by Transwell assay. Duplicated images are marked. ![file] ,
Androgen receptor promotes hepatitis B virus-induced hepatocarcinogenesis through modulation of hepatitis B virus RNA transcription
Authors: Yuh-Ling Chen
Charlotte Kathryn Ryan
Chawnshang Chang
Cheng-Lung Hsu
Ming-Heng Wu
Jing-Hsiung James Ou
Yao-Ching Hung
Wen-Lung Ma
Shuyuan Yeh
Journal: Science Translational Medicine (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Hepatitis B virus; androgen receptor; hepatocarcinogenesis; HBV-induced; hepatocellular carcinoma
Affiliations: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan.

Abstract:  Hepatitis B virus (HBV)-induced hepatitis and carcinogen-induced hepatocellular carcinoma (HCC) are associated with serum androgen concentration. However, how androgen or the androgen receptor (AR) contributes to HBV-induced hepatocarcinogenesis remains unclear. We found that hepatic AR promotes HBV-induced hepatocarcinogenesis in HBV transgenic mice that lack AR only in the liver hepatocytes (HBV-L-AR(-/y)). HBV-L-AR(-/y) mice that received a low dose of the carcinogen N'-N'-diethylnitrosamine (DEN) have a lower incidence of HCC and present with smaller tumor sizes, fewer foci formations, and less alpha-fetoprotein HCC marker than do their wild-type HBV-AR(+/y) littermates. We found that hepatic AR increases the HBV viral titer by enhancing HBV RNA transcription through direct binding to the androgen response element near the viral core promoter. This activity forms a positive feedback mechanism with cooperation with its downstream target gene HBx protein to promote hepatocarcinogenesis. Administration of a chemical compound that selectively degrades AR, ASC-J9, was able to suppress HCC tumor size in DEN-HBV-AR(+/y) mice. These results demonstrate that targeting the AR, rather than the androgen, could be developed as a new therapy to battle HBV-induced HCC. 

Retracted: No

PubPeer comments:
 The cell morphology of different groups in red boxes appear to look similar in Fig 7C. ![file] ,
Synthetic mammalian prions
Authors: Detlev Riesner
Stanley B Prusiner
Giuseppe Legname
Hoang-Oanh B Nguyen
Stephen J DeArmond
Ilia V Baskakov
Fred E Cohen
Journal: Science (2004)
Discipline: Multidisciplinary
Keywords: Recombinant mouse prion protein; amyloid fibrils; transgenic mice; neurologic dysfunction; protease-resistant PrP
Affiliations: Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA.

Abstract:  Recombinant mouse prion protein (recMoPrP) produced in Escherichia coli was polymerized into amyloid fibrils that represent a subset of beta sheet-rich structures. Fibrils consisting of recMoPrP(89-230) were inoculated intracerebrally into transgenic (Tg) mice expressing MoPrP(89-231). The mice developed neurologic dysfunction between 380 and 660 days after inoculation. Brain extracts showed protease-resistant PrP by Western blotting; these extracts transmitted disease to wild-type FVB mice and Tg mice overexpressing PrP, with incubation times of 150 and 90 days, respectively. Neuropathological findings suggest that a novel prion strain was created. Our results provide compelling evidence that prions are infectious proteins. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] *** Full figures and captions ![file] ,
Modelling science trustworthiness under publish or perish pressure
Authors: John P A Ioannidis
David Robert Grimes
Chris T Bauch
Journal: Royal Society Open Science (2018)
Discipline: Multidisciplinary
Keywords: public trust in science; publish or perish; research ethics; research fraud; science trustworthiness.
Affiliations: School of Mathematics and Physics, Queen’s University Belfast, BT7 1NN, UK, Department of Oncology, University of Oxford, Old Road Campus, Oxford OX3 7DQ, UK, Department of Applied Mathematics, University of Waterloo, 200 University Avenue W, Waterloo, Ontario, Canada N2L 3G1, Meta-Research Innovation Center at Stanford (METRICS), Stanford University, SPRC, MSOB X306, 1265 Welch Road, Stanford, CA 94305, USA, Department of Medicine, Stanford University, SPRC, MSOB X306, 1265 Welch Road, Stanford, CA 94305, USA, Department of Health Research and Policy, Stanford University, SPRC, MSOB X306, 1265 Welch Road, Stanford, CA 94305, USA, Department of Biomedical Data Science, Stanford University, SPRC, MSOB X306, 1265 Welch Road, Stanford, CA 94305, USA, Department of Statistics, Stanford University, SPRC, MSOB X306, 1265 Welch Road, Stanford, CA 94305, USA

Abstract:  Scientific publication is immensely important to the scientific endeavour. There is, however, concern that rewarding scientists chiefly on publication creates a perverse incentive, allowing careless and fraudulent conduct to thrive, compounded by the predisposition of top-tier journals towards novel, positive findings rather than investigations confirming null hypothesis. This potentially compounds a reproducibility crisis in several fields, and risks undermining science and public trust in scientific findings. To date, there has been comparatively little modelling on factors that influence science trustworthiness, despite the importance of quantifying the problem. We present a simple phenomenological model with cohorts of diligent, careless and unethical scientists, with funding allocated by published outputs. This analysis suggests that trustworthiness of published science in a given field is influenced by false positive rate, and pressures for positive results. We find decreasing available funding has negative consequences for resulting trustworthiness, and examine strategies to combat propagation of irreproducible science. 

Retracted: No

PubPeer comments:
 The same images used in six publications ![file] ![file] ![file] , 
 ![file] , 
 ![file] , 
 ![file] ,
Dynein interacts with the neural cell adhesion molecule (NCAM180) to tether dynamic microtubules and maintain synaptic density in cortical neurons
Authors: Adam G Hendricks
Mariko Tokito
Eran Perlson
Jacob E Lazarus
Erika L F Holzbaur
Keren Ben-Yaakov
Tal Gradus
Journal: Journal of Biological Chemistry (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cytoskeleton; Dynamic Instability; Dynein; Microtubules; NCAM
Affiliations: From the Department of Physiology and Pharmacology, Sackler Faculty of Medicine, and.

Abstract:  Cytoplasmic dynein is well characterized as an organelle motor, but dynein also acts to tether and stabilize dynamic microtubule plus-ends in vitro. Here we identify a novel and direct interaction between dynein and the 180-kDa isoform of the neural cell adhesion molecule (NCAM). Optical trapping experiments indicate that dynein bound to beads via the NCAM180 interaction domain can tether projecting microtubule plus-ends. Live cell assays indicate that the NCAM180-dependent recruitment of dynein to the cortex leads to the selective stabilization of microtubules projecting to NCAM180 patches at the cell periphery. The dynein-NCAM180 interaction also enhances cell-cell adhesion in heterologous cell assays. Dynein and NCAM180 co-precipitate from mouse brain extract and from synaptosomal fractions, consistent with an endogenous interaction in neurons. Thus, we examined microtubule dynamics and synaptic density in primary cortical neurons. We find that depletion of NCAM, inhibition of the dynein-NCAM180 interaction, or dampening of microtubule dynamics with low dose nocodazole all result in significantly decreased in synaptic density. Based on these observations, we propose a working model for the role of dynein at the synapse, in which the anchoring of the motor to the cortex via binding to an adhesion molecule mediates the tethering of dynamic microtubule plus-ends to potentiate synaptic stabilization. 

Retracted: No

PubPeer comments:
 Partially overlapped microscopy fields labelled as representing different experiments ![image] ,
Noonan syndrome/leukemia-associated gain-of-function mutations in SHP-2 phosphatase (PTPN11) enhance cell migration and angiogenesis
Authors: Keith R McCrae
Siying Wang
Wanming Zhang
Benjamin G Neel
Cheng-Kui Qu
Wen-Mei Yu
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: SHP-2; gain-of-function mutations; cell migration; beta1 integrin; ERK
Affiliations: Department of Medicine, Division of Hematology/Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio 44106, USA.

Abstract:  Mutations in SHP-2 phosphatase (PTPN11) that cause hyperactivation of its catalytic activity have been identified in Noonan syndrome and various childhood leukemias. Recent studies suggest that the gain-of-function (GOF) mutations of SHP-2 play a causal role in the pathogenesis of these diseases. However, the molecular mechanisms by which GOF mutations of SHP-2 induce these phenotypes are not fully understood. Here, we show that GOF mutations in SHP-2, such as E76K and D61G, drastically increase spreading and migration of various cell types, including hematopoietic cells, endothelial cells, and fibroblasts. More importantly, in vivo angiogenesis in SHP-2 D61G knock-in mice is also enhanced. Mechanistic studies suggest that the increased cell migration is attributed to the enhanced beta1 integrin outside-in signaling. In response to beta1 integrin cross-linking or fibronectin stimulation, activation of ERK and Akt kinases is greatly increased by SHP-2 GOF mutations. Also, integrin-induced activation of RhoA and Rac1 GTPases is elevated. Interestingly, mutant cells with the SHP-2 GOF mutation (D61G) are more sensitive than wild-type cells to the suppression of cell motility by inhibition of these pathways. Collectively, these studies reaffirm the positive role of SHP-2 phosphatase in cell motility and suggest a new mechanism by which SHP-2 GOF mutations contribute to diseases. 

Retracted: No

PubPeer comments:
 Bands in Figure 3A and 3C appear to overlap, but are described differently. Would the authors have access to the original scans? *** ![file] *** False color ![file] *** Full figure 3 ![file] , 
 ![file] ,
Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes
Authors: Kenneth Aldape
Farshad Nassiri
Shengrui Feng
Daniel D De Carvalho
Jeffrey A Zuccato
Craig Horbinski
Romina Nejad
Mathew R Voisin
Shu Yi Shen
Gelareh Zadeh
Ankur Chakravarthy
Vikas Patil
Journal: Nature Medicine (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Intracranial tumors; Diagnosis; Noninvasive; DNA-methylation profiles; Plasma
Affiliations: MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada., Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada., Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada., Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada. ., Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. ., Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. ., Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. .

Abstract:  Definitive diagnosis of intracranial tumors relies on tissue specimens obtained by invasive surgery. Noninvasive diagnostic approaches provide an opportunity to avoid surgery and mitigate unnecessary risk to patients. In the present study, we show that DNA-methylation profiles from plasma reveal highly specific signatures to detect and accurately discriminate common primary intracranial tumors that share cell-of-origin lineages and can be challenging to distinguish using standard-of-care imaging. 

Retracted: No

PubPeer comments:
 Readers should become aware of a recent preprint entitled Plasma-derived cell-free DNA methylomes might not enable detection and discrimination of intracranial tumors that calls into question part of the conclusions by Nassiri et al study. https: www.biorxiv.org content 10.1101 2021.06.02.446405v1 From the abstract: Intracranial tumors are both hard to detect and diagnose, resulting in poor patient outcomes. For that reason, non-invasive methods enabling detection and discrimination of intracranial tumors have significant clinical potential. **Recently Nassiri et al. propose plasma-derived cell-free DNA methylomes as such a method. Here I show that the results have been misinterpreted, and for many comparisons, no evidence supporting the conclusions are actually presented. While my analysis highlights the potential of plasma-derived cell-free DNA methylomes, the evidence provided by Nassiri et al. is simply currently insufficient.** ,
Phenotype of vigilin expressing breast cancer cells binding to the 69 nt 3′UTR element in CSF-1R mRNA
Authors: Demaretta Rush
Jha&#x27;nae B Stoffer
Setsuko K Chambers
Sang C Lee
Ho-Hyung Woo
Journal: Translational oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: Vigilin; CSF-1R; Breast cancer; Translation repression; 3-UTR element
Affiliations: The University of Arizona Cancer Center, 1515 N Campbell Ave, Tucson, AZ 85724, USA., Department of Pathology, University of Arizona, 1501 N Campbell Ave, Tucson, AZ 85724, USA., The University of Arizona Cancer Center, 1515 N Campbell Ave, Tucson, AZ 85724, USA; Department of Obstetrics and Gynecology, University of Arizona, 1501 N Campbell Ave, Tucson, AZ 85724, USA. Electronic address: .

Abstract:  Vigilin, a nucleocytoplasmic shuttling protein, post-transcriptionally suppresses proto-oncogene c-fms expression (encoding CSF-1R) in breast cancer by binding to a 69 nt cis-acting 3-UTR element in CSF-1R mRNA. CSF-1R is an important mediator of breast cancer development, metastasis, and survival. We confirm that vigilin decreases in vitro reporter luciferase activity as well as the translation rate of target mRNAs. We further explore the mechanism of suppression of CSF-1R. We show that the 69 nt binding element has profound effects on translation efficiency of CSF-1R mRNA, not seen in the presence of mutation of the element. Also, mutation of the 69 nt element in the CSF-1R mRNA 3'UTR both interferes with direct vigilin binding and obviates effect of vigilin overexpression on translational repression of CSF-1R. We show that stable vigilin binding requires the full length 69 nt CSF-1R element, including the 26 nt pyrimidine-rich core. Furthermore, titration of endogenous vigilin and other proteins which bind the 69 nt element, by exogenously introduced CSF-1R mRNA 3'UTR containing the pyrimidine-rich sequence, increases the adhesion, motility, and invasion of breast cancer cells. This phenotypic effect is not seen when the 69 nt element is deleted. Lastly, we are the first to show that human breast tissues exhibit strong vigilin expression in normal breast epithelium. Our pilot data suggest decreased vigilin protein expression, along with shift from the nucleus to the cytoplasmic location, in the transition to ductal carcinoma in situ. 

Retracted: No

PubPeer comments:
 ![file] Fig.4A. It seems lane 4 was spliced to the figure. ,
miR-200s contribute to interleukin-6 (IL-6)-induced insulin resistance in hepatocytes
Authors: Yong Man
Ting Zhao
Juan Jiao
Lilin Wang
Jian Li
Hangxiang Zhang
Lin Dou
Shu Wang
Xiuqing Huang
Dan Gao
Tao Shen
Journal: Journal of Biological Chemistry (2013)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: AKT; Glycogen; Glycogen Synthase Kinase 3; Interleukin; MicroRNA.
Affiliations: Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

Abstract:  By influencing the activity of the PI3K/AKT pathway, IL-6 acts as an important regulator of hepatic insulin resistance. miR-200s have been shown to control growth by regulating PI3K, but the role of miR-200s in the development of hepatic insulin resistance remains unclear. The present study showed that elevated serum concentration of IL-6 is associated with decreased levels of miR-200s, impaired activation of the AKT/glycogen synthase kinase (GSK) pathway, and reduced glycogenesis that occurred in the livers of db/db mice. As shown in the murine NCTC 1469 hepatocytes and the primary hepatocytes treated with 10 ng/ml IL-6 for 24 h and in 12-week-old male C57BL/6J mice injected with 16 μg/ml IL-6 by pumps for 7 days, IL-6 administration induced insulin resistance through down-regulation of miR-200s. Moreover, IL-6 treatment inhibited the phosphorylation of AKT and GSK and decreased the glycogenesis. The effects of IL-6 could be diminished by suppression of FOG2 expression. We concluded that IL-6 treatment may impair the activities of the PI3K/AKT/GSK pathway and inhibit the synthesis of glycogen, perhaps via down-regulating miR-200s while augmenting FOG2 expression. 

Retracted: No

PubPeer comments:
 ![file] , 
 To whom it may concern: Thank you for bringing to my attention the fact that two panels (AKT and GSK) in figure.4C of my article entitled: miR-200s contribute to interleukin-6 (IL-6)-induced insulin resistance in hepatocytes, The Journal of biological chemistry (2013), appear to be identical. The original data from three independent experiments are showed as follow. After checking the original data carefully, I found that we mistook GSK panel for AKT panel during the figure preparation. I sincerely apologize for this mistake and inconvenience this may have caused to the readers. I agree that this is a very serious matter. And I am deeply sorry for the mistake and take full responsibility for the outcome. I will contact the journal editor to correct this issue and provide updated version. Thank you again for your comment. All the best, Yours sincerely, Jian Li ![file] ,
BubR1 allelic effects drive phenotypic heterogeneity in mosaic-variegated aneuploidy progeria syndrome
Authors: Bjorn Bakker
Karthik B Jeganathan
Cheng Zhang
Hu Li
Jan M van Deursen
Darren J Baker
Cynthia J Sieben
Floris Foijer
Willemijn H van Deursen
Ines Sturmlechner
Grace G Nelson
Journal: Journal of Clinical Investigation (2020)
Discipline: CLINICAL MEDICINE
Keywords: Aging; Cancer; Cellular senescence; Genetic diseases; Oncology.
Affiliations: Departments of Biochemistry and Molecular Biology., Pediatric and Adolescent Medicine, and., Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA., European Research Institute for the Biology of Aging, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Abstract:  Mosaic-variegated aneuploidy (MVA) syndrome is a rare childhood disorder characterized by biallelic BUBR1, CEP57, or TRIP13 aberrations; increased chromosome missegregation; and a broad spectrum of clinical features, including various cancers, congenital defects, and progeroid pathologies. To investigate the mechanisms underlying this disorder and its phenotypic heterogeneity, we mimicked the BUBR1L1012P mutation in mice (BubR1L1002P) and combined it with 2 other MVA variants, BUBR1X753 and BUBR1H, generating a truncated protein and low amounts of wild-type protein, respectively. Whereas BubR1X753/L1002P and BubR1H/X753 mice died prematurely, BubR1H/L1002P mice were viable and exhibited many MVA features, including cancer predisposition and various progeroid phenotypes, such as short lifespan, dwarfism, lipodystrophy, sarcopenia, and low cardiac stress tolerance. Strikingly, although these mice had a reduction in total BUBR1 and spectrum of MVA phenotypes similar to that of BubR1H/H mice, several progeroid pathologies were attenuated in severity, which in skeletal muscle coincided with reduced senescence-associated secretory phenotype complexity. Additionally, mice carrying monoallelic BubR1 mutations were prone to select MVA-related pathologies later in life, with predisposition to sarcopenia correlating with mTORC1 hyperactivity. Together, these data demonstrate that BUBR1 allelic effects beyond protein level and aneuploidy contribute to disease heterogeneity in both MVA patients and heterozygous carriers of MVA mutations. 

Retracted: No

PubPeer comments:
 Figure 2E. * Red boxes: The BubR1 + L1002P and BubRR1+ - panels appear to show an overlap. Could the authors please check? ![file] , 
 #1 Dr. Bik: Thank you for identifying this concern. I was wondering what you believe the proper approach should be in a situation where the corresponding author may not be in a position to reply (as may be the situation [here] ? , 
 2020 correction. https: www.jci.org articles view 144781 During the preparation of this manuscript, the same sample was inadvertently included for the + L1002P and + u2013 images in Figure 2E. The authors were able to use the original samples to prepare a corrected version. ,
C29 sterols with a cyclopropane ring at C-25 and 26 from the Vietnamese marine sponge Ianthella sp. and their anticancer properties
Authors: Hee-Kyoung Kang
Thu Ha Tran
Van Kiem Phan
Huu Tung Nguyen
Thanh Huong Hoang
Tien Dat Nguyen
Van Minh Chau
Bui Huu Tai
Xuan Nhiem Nguyen
Jae-Hee Hyun
Young Ho Kim
Journal: Bioorganic & Medicinal Chemistry Letters (2009)
Discipline: CHEMISTRY
Keywords: C(29) sterols; cyclopropane ring; petrosterol-3,6-dione; 5alpha,6alpha-epoxy-petrosterol; Vietnamese marine sponge
Affiliations: College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.

Abstract:  Two new C(29) sterols with a cyclopropane ring at C-25 and C-26, petrosterol-3,6-dione (1) and 5alpha,6alpha-epoxy-petrosterol (2), along with petrosterol (3), were isolated from the Vietnamese marine sponge Ianthella sp. The structures of the new compounds were elucidated by comprehensive spectroscopic analyses. Compounds 1-3 showed cytotoxic activities on A549, HL-60, MCF-7, SK-OV-3, and U937 cancer cell lines with IC(50) in the range of 8.4-22.6 microM, whereas compounds 1-3 exhibited only weak cytotoxic activities on HT-29 cell. After HL-60 cells were treated with the compounds, several apoptosis events like chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. These data supported that the compounds might have potential for leukemia treatment. 

Retracted: No

PubPeer comments:
 This is the follow-up investigation after one research misconduct detected from the pubpeer for one of the author (HTN). Figure 5 in this manuscript is duplicated with Figure 2 in this one: https: pubpeer.com publications 9ED7C1A6365AE7969FAF3AAE0C6078#null Here is the evidence:  Left is figure 2 from 10.1016 j.bmcl.2010.09.074 and  right is Figure 5 in this article ![file] ,
Proteomic profiling of cereal aphid saliva reveals both ubiquitous and adaptive secreted proteins
Authors: Tom L Wilkinson
Sohail A K Rao
James C Carolan
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: salivary proteins; cereal aphid species; tandem mass spectrometry; protein identification; pea aphid genome assembly
Affiliations: School of Biology and Environmental Science, University College Dublin, Dublin, Ireland.

Abstract:  The secreted salivary proteins from two cereal aphid species, Sitobion avenae and Metopolophium dirhodum, were collected from artificial diets and analysed by tandem mass spectrometry. Protein identification was performed by searching MS data against the official protein set from the current pea aphid (Acyrthosiphon pisum) genome assembly and revealed 12 and 7 proteins in the saliva of S. avenae and M. dirhodum, respectively. When combined with a comparable dataset from A. pisum, only three individual proteins were common to all the aphid species; two paralogues of the GMC oxidoreductase family (glucose dehydrogenase; GLD) and ACYPI009881, an aphid specific protein previously identified as a putative component of the salivary sheath. Antibodies were designed from translated protein sequences obtained from partial cDNA sequences for ACYPI009881 and both saliva associated GLDs. The antibodies detected all parent proteins in secreted saliva from the three aphid species, but could only detect ACYPI009881, and not saliva associated GLDs, in protein extractions from the salivary glands. This result was confirmed by immunohistochemistry using whole and sectioned salivary glands, and in addition, localised ACYPI009881 to specific cell types within the principal salivary gland. The implications of these findings for the origin of salivary components and the putative role of the proteins identified are discussed in the context of our limited understanding of the functional relationship between aphid saliva and the plants they feed on. The mass spectrometry data have been deposited to the ProteomeXchange and can be accessed under the identifier PXD000113. 

Retracted: No

PubPeer comments:
 Figure 3B. * Red boxes: Two lanes appear to show an overlap, albeit zoomed differently. ![file] , 
 Figure S3. * Purple boxes: Panels A (SHP localization) and D (GLD localization) look very similar. ![file] ,
MiR-139-3p induces cell apoptosis and inhibits metastasis of cervical cancer by targeting NOB1
Authors: Ping Huang
Shikai Liu
Jie Xi
Journal: Biomedicine & Pharmacotherapy (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Cervical cancer; Invasion; Migration; NOB1; Proliferation
Affiliations: Department of gynaecology, Cangzhou Central Hospital, CangZhou, 061000, China. Electronic address: ., Department of gynaecology, Cangzhou Central Hospital, CangZhou, 061000, China.

Abstract:  MicroRNAs (miRNAs) play an important role in the development of various cancers, including cervical cancer (CC). The dysregulation of miRNA expression is associated with oncogenic transformation and miRNA often act as tumor suppressors. In this study, we aimed to analyze the effect on and mechanism of miR-139-3p in the progression of CC. The result of real-time PCR showed that miR-139-3p was down-regulated in CC tissues and cell lines. Overexpression of miR-139-3p significantly suppressed HeLa cell proliferation, migration and invasion and induced cell apoptosis. Bioinformatics analysis and luciferase reporter gene assay confirmed that NOB1 was targeted by miR-139-3p at the 3'-untranslated region (3'UTR) of its mRNA sequence. Furthermore, overexpression of NOB1 counteracted the effects of miR-139-3p suppression. Our results suggest that miR-139-3p may act as a tumor suppressor that can inhibit CC cell proliferation, migration and invasion and induce cell apoptosis through down-regulation of NOB1 expression. Taken together, this study provides a novel potential therapeutic strategy for the treatment of CC. 

Retracted: No

PubPeer comments:
 From the Department of Unexpected Similarities: Figure 2E. ![file] Here dramatised by color-reversing the Control Mimic panel and superimposing it on the miR Mimic panel, so that points cancel out if they are shared in common. ![file] , 
 Fig 4E. More unexpectedly similar panels. ![file] Pairing Untreated with Control , and miR Mimic with miR Mimic+pcDNA : ![file] ,