PReD-Bench/PRed-Bench huggingface dataset:
A novel NF-kappa B-inducing kinase-MAPK signaling pathway up-regulates NF-kappa B activity in melanoma cells
Authors: Ann Richmond
Punita Dhawan
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NF-kappa B; IKK; NIK; CXCL1; melanoma cells
Affiliations: Department of Veterans Affairs, Nashville, Tennessee 37212, USA.

Abstract:  Constitutive activation of NF-kappa B is an emerging hallmark of various types of tumors including breast, colon, pancreatic, ovarian, and melanoma. In melanoma cells, the basal expression of the CXC chemokine, CXCL1, is constitutively up-regulated. This up-regulation can be attributed in part to constitutive activation of NF-kappa B. Previous studies have shown an elevated basal I kappa B kinase (IKK) activity in Hs294T melanoma cells, which leads to an increased rate of I kappa B phosphorylation and degradation. This increase in I kappa B-alpha phosphorylation and degradation leads to an approximately 19-fold higher nuclear localization of NF-kappa B. However, the upstream IKK kinase activity is up-regulated by only about 2-fold and cannot account for the observed increase in NF-kappa B activity. We now demonstrate that NF-kappa B-inducing kinase (NIK) is highly expressed in melanoma cells, and IKK-associated NIK activity is enhanced in these cells compared with the normal cells. Kinase-dead NIK blocked constitutive NF-kappa B or CXCL1 promoter activity in Hs294T melanoma cells, but not in control normal human epidermal melanocytes. Transient overexpression of wild type NIK results in increased phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), which is inhibited in a concentration-dependent manner by PD98059, an inhibitor of p42/44 MAPK. Moreover, the NF-kappa B promoter activity decreased with overexpression of dominant negative ERK expression constructs, and EMSA analyses further support the hypothesis that ERK acts upstream of NF-kappa B and regulates the NF-kappa B DNA binding activity. Taken together, our data implicate involvement of I kappa B kinase and MAPK signaling cascades in NIK-induced constitutive activation of NF-kappa B. 

Retracted: No

PubPeer comments:
 The ACTIN panel (red box) was reused in different cell types in Figure 3A. ![file] ,
Long noncoding RNA HOXA-AS2 promotes cell migration and invasion via upregulating IGF-2 in non-small cell lung cancer as an oncogene
Authors: F-X Zheng
X-Q Wang
J Zhao
W-X Zheng
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; HOXA-AS2; metastasis; non-small cell lung cancer; QRT-PCR
Affiliations: Department of Radiotherapy, Liaocheng People's Hospital, Liaocheng, China. .

Abstract:  Objective: Recent studies have revealed the vital role of long non-coding RNAs (lncRNAs) in tumor progression. This study aims to determine whether lncRNA HOXA-AS2 functions in the metastasis of non-small cell lung cancer (NSCLC). Patients and methods: Quantitative Real Time-Polymerase Chain Reaction (QRT-PCR) was conducted to detect HOXA-AS2 expression in NSCLC tissues. Wound healing assay and transwell assay were performed to evaluate the function of HOXA-AS2 in mediating the behaviors of NSCLC cells. Furthermore, the interaction between IGF2 and HOXA-AS2 in mediating the metastasis of NSCLC was analyzed. Results: By comparing with the expression level in adjacent tissues, HOXA-AS2 expression was higher in NSCLC samples. Moreover, HOXA-AS2 knockdown inhibited invasion and migration of NSCLC cells and, conversely, HOXA-AS2 overexpression obtained the opposite results. In addition, the mRNA and protein expressions of IGF2 were downregulated via HOXA-AS2 knockdown. Besides, the expression of IGF2 was positively correlated to the expression of HOXA-AS2 in NSCLC tissues. Conclusions: In this work, HOXA-AS2 could enhance migratory and invasive abilities of NSCLC cells by upregulating IGF2, which might offer a potential therapeutic target for NSCLC. 

Retracted: No

PubPeer comments:
 This paper is one of a set of 121 papers that all contain images from the same library of about 100 photos and plots. This is unexpected, because each paper has different authors and different affiliations, with little to no overlap, and describes different cancer types and molecules. It would be very hard to explain how authors from different labs would all obtain the same photo. Therefore, the papers might have all be derived from the same source, such as a paper mill that sells ready-to-be-published papers. This  Stock Photo paper set has been described in more detail on my blog post, https: scienceintegritydigest.com 2020 07 05 the-stock-photo-paper-mill and in a Wall Street Journal article by Eva Xiao (currently behind a paywall): https: www.wsj.com articles chinese-research-papers-raise-doubts-fueling-global-questions-about-scientific-integrity-11593939600 The vast majority (113 121) of the papers were published in the same journal, European Review for Medical and Pharmacological Sciences (ERMPS). A link to the full set of papers can be found here: https: docs.google.com spreadsheets d 172RWS18w1lTNJ9Nnj80fuXXTqTm4fGkoK0sdYyvKE3g edit?usp=sharing All papers have been reported to the journal editors on July 2, 2020. ,
The novel cis-encoded small RNA h2cR is a negative regulator of hfq2 in Burkholderia cenocepacia
Authors: Jorge H Leitão
Christian G Ramos
Paulo J P da Costa
Gerd Döring
Journal: PLoS ONE (2012)
Discipline: Multidisciplinary
Keywords: sRNAs; regulatory mechanisms; target mRNAs; cis-encoded sRNA; h2cR
Affiliations: Institute for Biotechnology and Bioengineering, Instituto Superior Técnico, Universidade Técnica de Lisboa, Lisboa, Portugal.

Abstract:  Small non-coding regulatory RNAs (sRNAs) post-transcriptionally affect multiple phenotypes in prokaryotes and eukaryotes, yet most of the underlying regulatory mechanisms and the nature of the target mRNAs remain unclear. Here we report the identification and functional analysis of the novel cis-encoded sRNA h2cR, from the human opportunistic pathogen Burkholderia cenocepacia J2315. The sRNA was found to negatively regulate the hfq2 mRNA, through binding to part of the 5'-UTR region of the hfq2 mRNA, resulting in accelerated hfq2 mRNA decay and reduced protein levels in exponentially growing cells. Both the h2cR transcript and the hfq2 mRNA are stabilized by the other B. cenocepacia RNA chaperone, Hfq. Infection experiments using the nematode Caenorhabditis elegans revealed that down-regulation of Hfq2 by h2cR decreases the B. cenocepacia ability to colonize and persist within the nematode, suggesting a role for h2cR on bacterial persistence in the host. 

Retracted: No

PubPeer comments:
 Unexpected similarities between panels in Figure 2A: ![file] and Figure 3: ![file] , 
 There is also a problem in Figure 6, where the 5S bands in the first and third group look identical ![file] ,
Essential role for ADAM19 in cardiovascular morphogenesis
Authors: Umut Sahin
Riccardo Chiusaroli
Andrea Vortkamp
Katia Manova
Rebecca Hahn
Hong-Ming Zhou
Peter Fisher
Valérie Chesneau
Roland Baron
Gisela Weskamp
Barbara Hempstead
David Wilkes
Carl P Blobel
Keisuke Horiuchi
Craig T Basson
Journal: Molecular and Cellular Biology (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Congenital heart disease; ADAM19; cardiac morphogenesis; ventricular septal defect; valvular stenosis
Affiliations: Cell Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA., Cell Biology Program, Sloan-Kettering Institute, Department of Molecular and Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, Max Planck Institute for Molecular Genetics, Otto Warburg Laboratory, D14195 Berlin, Germany, Department of Orthopaedics and Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, Molecular Cardiology Laboratory, Cardiology Division, Department of Cell and Developmental Biology, Department of Anatomy and Cell Biology, Columbia University, New York, New York 10032, Molecular Cytology Core Facility, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, Hematology Division, Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021

Abstract:  Congenital heart disease is the most common form of human birth defects, yet much remains to be learned about its underlying causes. Here we report that mice lacking functional ADAM19 (mnemonic for a disintegrin and metalloprotease 19) exhibit severe defects in cardiac morphogenesis, including a ventricular septal defect (VSD), abnormal formation of the aortic and pulmonic valves, leading to valvular stenosis, and abnormalities of the cardiac vasculature. During mouse development, ADAM19 is highly expressed in the conotruncus and the endocardial cushion, structures that give rise to the affected heart valves and the membranous ventricular septum. ADAM19 is also highly expressed in osteoblast-like cells in the bone, yet it does not appear to be essential for bone growth and skeletal development. Most adam19(-/-) animals die perinatally, likely as a result of their cardiac defects. These findings raise the possibility that mutations in ADAM19 may contribute to human congenital heart valve and septal defects. 

Retracted: No

PubPeer comments:
 Figure 4. Splices in some panels, but not in others. ![file] ,
Unique preservation of neural cells in Hutchinson- Gilford progeria syndrome is due to the expression of the neural-specific miR-9 microRNA
Authors: Cécile Denis
Marc Peschanski
Nicolas Levy
Annachiara De Sandre-Giovannoli
Sophie Blondel
Yves Maury
Cécile Martinat
Xavier Nissan
Claire Navarro
Mathilde Girard
Journal: Cell Reports (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hutchinson-Gilford progeria syndrome; premature aging; cognitive impairment; induced pluripotent stem cells; lamin A
Affiliations: CECS, I-STEM, AFM, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, 5 rue Henri Desbruères, 91030 Evry cedex, France. 

Abstract:  One puzzling observation in patients affected with Hutchinson-Gilford progeria syndrome (HGPS), who overall exhibit systemic and dramatic premature aging, is the absence of any conspicuous cognitive impairment. Recent studies based on induced pluripotent stem cells derived from HGPS patient cells have revealed a lack of expression in neural derivatives of lamin A, a major isoform of LMNA that is initially produced as a precursor called prelamin A. In HGPS, defective maturation of a mutated prelamin A induces the accumulation of toxic progerin in patient cells. Here, we show that a microRNA, miR-9, negatively controls lamin A and progerin expression in neural cells. This may bear major functional correlates, as alleviation of nuclear blebbing is observed in nonneural cells after miR-9 overexpression. Our results support the hypothesis, recently proposed from analyses in mice, that protection of neural cells from progerin accumulation in HGPS is due to the physiologically restricted expression of miR-9 to that cell lineage. 

Retracted: No

PubPeer comments:
 Would the authors provide an explanation for the apparent similarities between the two following FACS panels in Figure 2B, which corresponded to the different experimental conditions? The colored circles and arrows show areas with unexpected similarities. ![file] , 
 The same photo has been used in figure 4A and figure S4C. The authors have mentioned that the photo presented in figure 4A and S4C are respectively related to the cells transfected with control vector and the untransfected cells. ![file] , 
 Dear Phrixocomes Ophiucha, Thank you for having read our paper in details. - Regarding the Figure 4A S4C this image refers to the same cells, same staining and the same treatment (treated with a premiR that doesnt target anything). For clarity, we decided at that time to add it in the supplementary figure 4 that provides more details on the same results shown in Fig 4A. - Regarding the FACS I dont have anymore access to the raw datas to check what happened here (it was done 12 years ago). I have done myself these flow cytometry experiments multiple times and everything was done each times in triplicates in several cell types and several cell lines. Have a nice day Xavier ,
Integration of apoptosis signal-regulating kinase 1-mediated stress signaling with the Akt/protein kinase B-IκB kinase cascade
Authors: Mary C Puckett
Haian Fu
Lisa M Cockrell
Fadlo Khuri
Andrea L Kasinski
Yuhong Du
Erinn H Goldman
Cun-Yu Wang
Anning Lin
Bei Huang
Hidenori Ichijo
Journal: Molecular and Cellular Biology (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cellular processes; signaling networks; reactive oxygen species; endoplasmic reticulum stress; survival factors
Affiliations: Department of Pharmacology, Emory University School of Medicine, Atlanta, GA, USA.

Abstract:  Cellular processes are tightly controlled through well-coordinated signaling networks that respond to conflicting cues, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress signals, and survival factors to ensure proper cell function. We report here a direct interaction between inhibitor of κB kinase (IKK) and apoptosis signal-regulating kinase 1 (ASK1), unveiling a critical node at the junction of survival, inflammation, and stress signaling networks. IKK can be activated by growth factor stimulation or tumor necrosis factor alpha engagement. IKK forms a complex with and phosphorylates ASK1 at a sensor site, Ser967, leading to the recruitment of 14-3-3, counteracts stress signal-triggered ASK1 activation, and suppresses ASK1-mediated functions. An inhibitory role of IKK in JNK signaling has been previously reported to depend on NF-κB-mediated gene expression. Our data suggest that IKK has a dual role: a transcription-dependent and a transcription-independent action in controlling the ASK1-JNK axis, coupling IKK to ROS and ER stress response. Direct phosphorylation of ASK1 by IKK also defines a novel IKK phosphorylation motif. Because of the intimate involvement of ASK1 in diverse diseases, the IKK/ASK1 interface offers a promising target for therapeutic development. 

Retracted: No

PubPeer comments:
 Figure 3H. * Pink arrows: Sharp vertical background transitions are visible in several panels. * Red arrows: Lanes 1-2 and lanes 3-4 in the Akt panel look very similar to each other. ![file] ,
Resistin-Like Molecule Beta (RELM-β) Regulates Proliferation of Human Diabetic Nephropathy Mesangial Cells via Mitogen-Activated Protein Kinases (MAPK) Signaling Pathway
Authors: Jun Shi
Bao-Ping Chen
Cong-Cong Fan
Yun-Qian Wang
Journal: Medical Science Monitor (2017)
Discipline: CLINICAL MEDICINE
Keywords: RELM-β; diabetic nephropathy; MAPK signaling pathways; human mesangial cells; proliferation
Affiliations: Department of Nephrology, Henan University Huaihe Hospital, Kaifeng, Henan, China (mainland)., Department of Endocrinology, Henan University Huaihe Hospital, Kaifeng, Henan, China (mainland).

Abstract:  BACKGROUND Resistin-like molecule beta (RELM-β) has been reported to be associated with diabetic nephropathy (DN). However, the role of RELM-β in DN is poorly understood. This study was conducted to delineate the underlying mechanisms of action and to investigate the role of RELM-β in the primitive development of DN via MAPK signaling pathways. MATERIAL AND METHODS Lentivirus-mediated vectors and RNAi technology were used to establish the model of RELM-β up-regulated and down-regulated expression in human mesangial cells (HMCs). The proliferation of HMCs was detected through CCK-8 method. The cell cycle and cell proliferation of HMCs was detected through flow cytometry. The MAPKs pathway protein activity was detected through Western blotting. RESULTS The HMCs with up-regulated and down-regulated expression of RELM-β increased or decreased significantly at 2-3 days. The HMCs with high glucose intervention reversed the proliferation inhibition. The HMCs with exogenous glucose or RELM-β protein intervention partially reversed the cell cycle inhibition. Among the MAPKs pathway, the phosphorylation activity of p38MAPK and JNK increased or decreased and ERK1/2 did not change in the overexpression or inhibition of RELM-β. The p38 MAPK pathway inhibitor SB202190 significantly inhibited the proliferation of HMCs caused by overexpression of RELM-β. Up-regulated expression of RELM-b induced the phosphorylation of p38 MAPK, JNK in HMCs and promoted HMCs proliferation and participated in early DN through the MAPKs pathway. CONCLUSIONS The results provide evidence that RELM-b is a potential molecular target for the treatment of DN. 

Retracted: Yes

PubPeer comments:
 Figure-2 : NMR spectra show very strange similar patterns for HA-PEG-PLGA and MPEG-PLGA ? ![file] ,
A Mn(II)-coordination polymer: selective detection of Fe3+ ion and treatment activity on sepsis via reducing the inflammatory cytokines releasing
Authors: Su, Xiaoqing
Yan, Shijie
Xu, Qian
Deng, Zhuojun
Journal: Journal of Polymer Research (2021)
Discipline: CHEMISTRY
Keywords: Mn(II)-based coordination polymer; luminescence; fluorescent probe; Fe3+ ion detection; sepsis treatment

Abstract: In the current research, a new Mn(II)-based coordination polymer, {(NH2Me)2[Mn4(Hntb)4(4,4′-bpy)(OH)2] DMF} (1) have been formed by mixing the ligands of H3ntb (4,4′,4′′-nitrilotris-benzoic) and 4,4′-bpy (4,4′-bipyridine). According to the results of UV detection, complex 1 has strong blue luminescence, which means that it can be used as a fluorescent probe for specific&nbsp;detection of Fe3+ ion in water with a Ksv value of 3.2\u2009×\u2009104&nbsp;M\u22121. Furthermore, the treatment activity of the compound on sepsis treatment was assessed and the protentional mechanism was revealed. Firstly, the inflammatory cytokines released into the plasma was measured with ELISA detection kit. Then, the survival rate of the infected animals was recorded after compound treatment.

Retracted: No

PubPeer comments:
 Could the authors comment on the relevance of these References?  Coordination polymers (CPs),which are based on metal ions and a variety of organic ligands, are not only widely used in gas accumulation, metal ion interchange, luminescence and catalysis, but also attracted peopleu2019s attention due to its unique aesthetic structure in the recent years [5u201310]. - [10]. Arshad M, Du HL, Javed MS, Maqsood A, Ashraf I, Hussain S, Ma WL, Ran HP (2020) Fabrication, structure, and frequency-dependent electrical and dielectric properties of Sr-doped BaTiO3 ceramics. Ceram Int 46:2238u20132246  CPs have many important functions, such as catalysis, inclusion and molecular screening. At the same time, CPs play an important role in the development of functional molecule-based substances. Therefore, the design and synthesis of CPs has always been the focus of attention, although there are still many challenges in predicting the function and structure of CPs [11u201317] - [11]. Chen Z, Ahn H (2020) Item Response Theory Based Ensemble in Machine Learning. Int J Autom Comput 17:621u2013636 - [12]. Zhao J, Zhang J, Zhang D, Hu Z, Sun Y (2021) Effect of emerging pollutant fluoxetine on the excess sludge anaerobic digestion. Sci Total Environ 752:141932 --------------------------  This **preformation** was finished under the illustration of the manufacturers with some changes. In brief, 50 mice used in the study were obtained from Zhejiang university (Hangzhou, China), and then kept at the standard condition with free water and food. All the **preformation** in this experiment was admitted by the Ethics Committee of the Zhejiang university (Hangzhou, China).  Preformation , in this sense of conducting an experiment, is an odd choice of word. I have only encountered it in [the products of a prolific papermill] , specialising in a genre of  Floor-wax-AND-a-dessert-topping papers. ![] ,
Epigenetic clocks reveal a rejuvenation event during embryogenesis followed by aging
Authors: Csaba Kerepesi
Bohan Zhang
Sang-Goo Lee
Alexandre Trapp
Vadim N Gladyshev
Journal: Science Advances (2021)
Discipline: Multidisciplinary
Keywords: germ line; aging; rejuvenation; epigenetic clock; biological age
Affiliations: Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.

Abstract:  The notion that the germ line does not age goes back to the 19th-century ideas of August Weismann. However, being metabolically active, the germ line accumulates damage and other changes over time, i.e., it ages. For new life to begin in the same young state, the germ line must be rejuvenated in the offspring. Here, we developed a multi-tissue epigenetic clock and applied it, together with other aging clocks, to track changes in biological age during mouse and human prenatal development. This analysis revealed a significant decrease in biological age, i.e., rejuvenation, during early stages of embryogenesis, followed by an increase in later stages. We further found that pluripotent stem cells do not age even after extensive passaging and that the examined epigenetic age dynamics is conserved across species. Overall, this study uncovers a natural rejuvenation event during embryogenesis and suggests that the minimal biological age (ground zero) marks the beginning of organismal aging. 

Retracted: No

PubPeer comments:
 https: twitter.com mkaeberlein status 1408986689402327041 https: twitter.com DrMorganLevine status 1408989087374233602 https: twitter.com DPromislow status 1408993227147943936 ,
Loss of protein kinase Cepsilon results in impaired cutaneous wound closure and myofibroblast function
Authors: Andrew Leask
Mark Eastwood
Alan Holmes
Yunliang Chen
Christopher P Denton
David J Abraham
Korsa Khan
Carol M Black
Xu Shi-Wen
Journal: Journal of cell science (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cutaneous wound repair; fibroblast; myofibroblast; alpha-SMA; ECM
Affiliations: CIHR Group in Skeletal Development and Remodeling, Division of Oral Biology and Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London ON, Canada N6A 5C1. 

Abstract:  Cutaneous wound repair requires the de novo induction of a specialized form of fibroblast, the alpha-smooth muscle actin (alpha-SMA)-expressing myofibroblast, which migrates into the wound where it adheres to and contracts extracellular matrix (ECM), resulting in wound closure. Persistence of the myofibroblast results in scarring and fibrotic disease. In this report, we show that, compared with wild-type littermates, PKCepsilon-/- mice display delayed impaired cutaneous wound closure and a reduction in myofibroblasts. Moreover, both in the presence and absence of TGFbeta, dermal fibroblasts from PKCepsilon-/- mice cultured on fibronectin show impaired abilities to form ;supermature' focal adhesions and alpha-SMA stress fibers, and reduced pro-fibrotic gene expression. Smad3 phosphorylation in response to TGFbeta1 was impaired in PKCepsilon-/- fibroblasts. PKCepsilon-/- fibroblasts show reduced FAK and Rac activation, and adhesive, contractile and migratory abilities. Overexpressing constitutively active Rac1 rescues the defective FAK phosphorylation, cell migration, adhesion and stress fiber formation of these PKCepsilon-/- fibroblasts, indicating that Rac1 operates downstream of PKCepsilon, yet upstream of FAK. These results suggest that loss of PKCepsilon severely impairs myofibroblast formation and function, and that targeting PKCepsilon may be beneficial in selectively modulating wound healing and fibrotic responses in vivo. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
 2014 correction. https: jcs.biologists.org content 127 15 3396 In Fig.u20053B, a western blot showing the total input protein for the immunoprecipitation was not shown. The corrected figure with total protein levels identified is as shown below. An equal amount of total cell-derived protein were used to assess the interaction of FAK with paxillin (PAX) and vimentin (VIM). In Fig.u20057B, the immunoprecipitation experiment for activated Rac was presented without control western blots showing total input protein and total level of Rac protein in the samples. The corrected figure is as shown below. ,
MicroRNA-101-3p suppresses cell proliferation, invasion and enhances chemotherapeutic sensitivity in salivary gland adenoid cystic carcinoma by targeting Pim-1
Authors: Yun-Long Wang
Chen Zhang
Zhi-Jian Liu
Xiao-Yu Liu
Hong He
Journal: American journal of cancer research (2015)
Discipline: CLINICAL MEDICINE
Keywords: ACC; Pim-1; chemotherapeutic sensitivity; miR-101-3p.
Affiliations: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University Wuhan, China., The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University Wuhan, China ; Department of Orthodontics, School & Hospital of Stomatology, Wuhan University Wuhan, China.

Abstract:  MicroRNAs (miRNAs) play critical roles in carcinogenesis and tumor progression. Recent research has revealed miR-101-3p as an important regulator in several cancers. Nevertheless, its function in salivary gland Adenoid cystic carcinoma (ACC), a relatively rare malignance with poor long-term survival rate arisen in head and neck region, remain unknown. In this study, down-regulated miR-101-3p expression was detected in ACC tissues and ACC cell lines with high potential for metastasis. Ectopic expression of miR-101-3p significantly repressed the invasion, proliferation, colony formation, and formation of nude mice xenografts and induced potent apoptosis in ACC cell lines. The provirus integration site for Moloney murine leukemia virus 1 (Pim-1) oncogene was subsequently confirmed as a direct target gene of miR-101-3p in ACC. Functional restoration assays revealed that miR-101-3p inhibits cell growth and invasion by directly decreasing Pim-1 expression. Protein levels of Survivin, Cyclin D1 and β-catenin were also down-regulated by miR-101-3p. miR-101-3p enhanced the sensitivity of cisplatin in ACC cell lines. Taken together, our results demonstrate that the novel miR-101-3p/Pim-1 axis provides excellent insights into the carcinogenesis and tumor progression of ACC and may be a promising therapeutic target for this type of cancer. 

Retracted: No

PubPeer comments:
 https: portlandpress.com bioscirep article 40 7 BSR-20180177_EOC 225854 Expression-of-Concern-Association-of-Fc-RI u201cThe Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, as commented on in the correspondence u201cComments on u2018Association of Fcu03b5RIu03b2 polymorphisms with risk of asthma and allergic rhinitis: evidence based on 29 case-control studiesu2019u201d, and therefore has issued an expression of concern to notify readers to potential errors in the conclusions. The authors were invited to respond to the comments made, but have not responded.u201d That u201ccorrespondenceu201d can be found here: https: doi.org 10.1042 BSR20193424 ,
Specificity protein 1-dependent p53-mediated suppression of human manganese superoxide dismutase gene expression
Authors: Sanjit Kumar Dhar
Yumin Chen
Daret K St Clair
Yong Xu
Journal: Journal of Biological Chemistry (2006)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Manganese superoxide dismutase; Sp1; Nucleophosmin; NF-kappaB; p53
Affiliations: Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536, USA.

Abstract:  Manganese superoxide dismutase (MnSOD) is a primary antioxidant enzyme necessary for the survival of aerobic life. Previously, we demonstrated that specificity protein 1 (Sp1) is essential for the basal transcription of the MnSOD gene. We also identified nucleophosmin (NPM), an RNA-binding protein, as an important co-activator of NF-kappaB in the induction of MnSOD by cytokine and tumor promoter. Here, using chromatin immunoprecipitation (ChIP) analysis, we demonstrate that Sp1 and NPM interact in vivo to enhance NF-kappaB-mediated MnSOD induction. Interaction between NPM and Sp1 or NF-kappaB at the promoter and enhancer of the MnSOD gene in vivo were verified by the presence of the PCR products from the promoter and enhancer elements in the ChIP assay. Unexpectedly, we also found p53, another transcription factor, to be a component of the complex detected by ChIP assay. The presence of p53 in this transcription complex was verified by immunoprecipitation of p53 proteins with antibody to Sp1 in nuclear extracts. Using a vector expressing full-length p53 cDNA, we demonstrated that p53 overexpression suppresses MnSOD mRNA and protein levels. Consistent with the negative role of p53 in the expression of the MnSOD gene, expression of small interfering RNA for p53 leads to an increase of MnSOD mRNA and protein levels. Using ChIP assays and immunoprecipitation, we further demonstrated that p53 interacts with Sp1 to suppress both the constitutive and 12-O-tetradecanoylphorbol-13-acetate-stimulated expression of the MnSOD gene. Inhibition of the MnSOD gene by p53 was abolished when Sp1 sites on the MnSOD promoter were mutated or when the Sp1 protein was reduced by siRNA approaches. Because expression of MnSOD protects against cell death, our findings reveal a previously unrecognized mechanism of p53-mediated cell death and demonstrate an intricate relationship between the positive and negative control of MnSOD expression. 

Retracted: No

PubPeer comments:
 ![file] ![file] ,
Repetitive Transcranial Magnetic Stimulation Over the Left Posterior Middle Temporal Gyrus Reduces Wrist Velocity During Emblematic Hand Gesture Imitation
Authors: Arran T Reader
Nicholas P Holmes
Journal: Brain Topography (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Action recognition; Apraxia; Dual-route; Kinematics; Semantic storage
Affiliations: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. ., Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK. ., School of Psychology, University of Nottingham, Nottingham, UK.

Abstract:  Results from neuropsychological studies, and neuroimaging and behavioural experiments with healthy individuals, suggest that the imitation of meaningful and meaningless actions may be reliant on different processing routes. The left posterior middle temporal gyrus (pMTG) is one area that might be important for the recognition and imitation of meaningful actions. We studied the role of the left pMTG in imitation using repetitive transcranial magnetic stimulation (rTMS) and two-person motion-tracking. Participants imitated meaningless and emblematic meaningful hand and finger gestures performed by a confederate actor whilst both individuals were motion-tracked. rTMS was applied during action observation (before imitation) over the left pMTG or a vertex control site. Since meaningless action imitation has been previously associated with a greater wrist velocity and longer correction period at the end of the movement, we hypothesised that stimulation over the left pMTG would increase wrist velocity and extend the correction period of meaningful actions (i.e., due to interference with action recognition). We also hypothesised that imitator accuracy (actor-imitator correspondence) would be reduced following stimulation over the left pMTG. Contrary to our hypothesis, we found that stimulation over the pMTG, but not the vertex, during action observation reduced wrist velocity when participants later imitated meaningful, but not meaningless, hand gestures. These results provide causal evidence for a role of the left pMTG in the imitation of meaningful gestures, and may also be in keeping with proposals that left posterior temporal regions play a role in the production of postural components of gesture. 

Retracted: No

PubPeer comments:
 This paper was criticised as part of a self-reflection posted on Twitter on 2nd-3rd April, 2021 (twitter TheHandLab status 1377760796130869248) Criticism: The most interesting comparisons in this paper are between conditions (meaningful vs. meaningless actions), but the TMS control condition (vertex) used here is weak. I ve long known that vertex is basically the same as no TMS if you are comparing it to any other scalp area associated with higher annoyance ,
Aspirin increases metabolism through germline signalling to extend the lifespan of Caenorhabditis elegans
Authors: Qin-Li Wan
Xiao-Ming He
Xiao-Hui Mu
Huai-Rong Luo
Xiao-Bing Huang
Gui-Sheng Wu
Journal: PLoS ONE (2017)
Discipline: Multidisciplinary
Keywords: Aspirin; aging; lifespan; metabolism; Caenorhabditis elegans
Affiliations: Key Laboratory for Aging and Regenerative Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China., State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, China., Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, China., University of Chinese Academy of Sciences, Beijing, China.

Abstract:  Aspirin is a prototypic cyclooxygenase inhibitor with a variety of beneficial effects on human health. It prevents age-related diseases and delays the aging process. Previous research has shown that aspirin might act through a dietary restriction-like mechanism to extend lifespan. To explore the mechanism of action of aspirin on aging, we determined the whole-genome expression profile of Caenorhabditis elegans treated with aspirin. Transcriptome analysis revealed the RNA levels of genes involved in metabolism were primarily increased. Reproduction has been reported to be associated with metabolism. We found that aspirin did not extend the lifespan or improve the heat stress resistance of germline mutants of glp-1. Furthermore, Oil Red O staining showed that aspirin treatment decreased lipid deposition and increased expression of lipid hydrolysis and fatty acid β-oxidation-related genes. The effect of germline ablation on lifespan was mainly mediated by DAF-12 and DAF-16. Next, we performed genetic analysis with a series of worm mutants and found that aspirin did not further extend the lifespans of daf-12 and daf-16 single mutants, glp-1;daf-12 and glp-1;daf-16 double mutants, or glp-1;daf-12;daf-16 triple mutants. The results suggest that aspirin increase metabolism and regulate germline signalling to activate downstream DAF-12 and DAF-16 to extend lifespan. 

Retracted: No

PubPeer comments:
 Figure 3C it seems to contain an image duplication in glp-1 worms treated with Aspirin (right picture was resized). ![file] Figure 4G also contains image duplication (daf-12(rh274)) control? ![file] A minor point: Lifespan extension by aspirin could not be replicated by the Caenorhabditis Intervention Testing Program in N2. (Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects, 10.1038 ncomms14256) ,
NK cells kill mycobacteria directly by releasing perforin and granulysin
Authors: Tsung-Teng Huang
Chih-Jung Chang
Ya-Jing Hsu
David M Ojcius
Chia-Chen Lu
Jan Martel
Tsu-Lan Wu
Ting-Shu Wu
John D Young
Chuan-Sheng Lin
Hsin-Chih Lai
Ju-Hsin Chia
Journal: Journal of leukocyte biology (2014)
Discipline: IMMUNOLOGY
Keywords: NCR; NKG2D; antibacterial activity; innate immunity; tuberculosis.
Affiliations: Department of Respiratory Therapy, College of Medicine, Fu Jen Catholic University, Taipei, Taiwan;, Department of Internal Medicine, Division of Infectious Diseases, and Graduate Institute of Clinical Medical Sciences and., Departments of Medical Biotechnology and Laboratory Sciences and., Microbiology and Immunology, College of Medicine., Department of Clinical Pathology, Linkou Chang Gung Memorial Hospital, Kweishan, Taiwan;, Departments of Medical Biotechnology and Laboratory Sciences and Research Center of Bacterial Pathogenesis, and Center for Molecular and Clinical Immunology, Chang Gung University, Kweishan, Taiwan;, Center for Molecular and Clinical Immunology, Chang Gung University, Kweishan, Taiwan;, Center for Molecular and Clinical Immunology, Chang Gung University, Kweishan, Taiwan; Health Sciences Research Institute and Department of Molecular Cell Biology, University of California, Merced, California, USA;, Center for Molecular and Clinical Immunology, Chang Gung University, Kweishan, Taiwan; Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York, USA; and Biochemical Engineering Research Center, Ming Chi University of Technology, Taipei, Taiwan  ., Departments of Medical Biotechnology and Laboratory Sciences and Research Center of Bacterial Pathogenesis, and Center for Molecular and Clinical Immunology, Chang Gung University, Kweishan, Taiwan;  .

Abstract:  Although the mechanisms underlying the cytotoxic effect of NK cells on tumor cells and intracellular bacteria have been studied extensively, it remains unclear how these cells kill extracellular bacterial pathogens. In this study, we examine how human NK cells kill Mycobacterium kansasii and M.tb. The underlying mechanism is contact dependent and requires two cytolytic proteins: perforin and granulysin. Mycobacteria induce enhanced expression of the cytolytic proteins via activation of the NKG2D/NCR cell-surface receptors and intracellular signaling pathways involving ERK, JNK, and p38 MAPKs. These results suggest that NK cells use similar cellular mechanisms to kill both bacterial pathogens and target host cells. This report reveals a novel role for NK cells, perforin, and granulysin in killing mycobacteria and highlights a potential alternative defense mechanism that the immune system can use against mycobacterial infection. 

Retracted: No

PubPeer comments:
 Figure 2D and 5Ai: * Red boxes: Four lanes in the  granulysin panel of Figure 2D look similar to four lanes in the  GAPDH panel of Figure 5Ai. ![file] ,
Characterization of the mechanisms controlling Greatwall activity
Authors: Thierry Lorca
Aicha Gharbi-Ayachi
Anne-Aurélie Raymond
Andrew Burgess
Bernard Monsarrat
Jean-Claude Labbé
Anna Castro
Gilles Labesse
Suzanne Vigneron
Journal: Molecular and Cellular Biology (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Greatwall; Gwl; AGC kinase; hydrophobic motif; molecular modeling
Affiliations: Universités Montpellier 2 et 1, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, IFR 122, 1919 Route de Mende, 34293 Montpellier cedex 5, France., Universités Montpellier 2 et 1, Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, IFR 122, 1919 Route de Mende, 34293 Montpellier cedex 5, France, Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, 205 Route de Narbonne, 31077 Toulouse Cedex 4, France, Université de Toulouse III, IPBS, CNRS, Toulouse, France, Centre de Biochimie Structurale, INSERM U554, CNRS UMR 5048, UM1, 29 Rue de Navacelles, 34060 Montpellier Cedex, France

Abstract:  Here we investigate the mechanisms regulating Greatwall (Gwl), a serine/threonine kinase essential for promoting the correct timing of mitosis. We identify Gwl as a unique AGC kinase that, unlike most AGC members, appears to be devoid of a hydrophobic motif despite the presence of a functional hydrophobic pocket. Our results suggest that Gwl activation could be mediated by the binding of its hydrophobic pocket to the hydrophobic motif of another AGC kinase. Our molecular modeling and mutagenic analysis also indicate that Gwl displays a conserved tail/linker site whose phosphorylation mediates kinase activation by promoting the interaction of this phosphorylated residue with two lysines at the N terminus. This interaction could stabilize the αC-helix and maintain kinase activity. Finally, the different phosphorylation sites on Gwl are identified, and the role of each one in the regulation of Gwl kinase activity is determined. Our data suggest that only the phosphorylation of the tail/linker site, located outside the putative T loop, appears to be essential for Gwl activation. In summary, our results identify Gwl as a member of the AGC family of kinases that appears to be regulated by unique mechanisms and that differs from the other members of this family. 

Retracted: No

PubPeer comments:
 July 2017 correction found here: https: mcb.asm.org content 37 14 e00231-17 It reads:  *Fig. 7D, right: An error was made during the assembly of the figure that resulted in an inadvertent duplication in the second panel. The corrected image is shown below.* Here is the original Figure 7, reported to the journal in September 2016, with the duplicated panels marked in red. ![file] I thank the authors for correcting this error. This paper was part of a structured search for image duplications in Molecular and Cellular Biology paper, which was published here: https: mcb.asm.org content 38 20 e00309-18.long ,
MiR-24 alleviates cardiomyocyte apoptosis after myocardial infarction via targeting BIM
Authors: Y Ling
X Wang
L-J Pan
H Gong
Journal: European Review for Medical and Pharmacological Sciences (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Ischemia hypoxia; cardiomyocyte apoptosis; acute myocardial infarction; BIM; miR-24
Affiliations: Division of Cardiology, Department of Medicine, Jinshan Hospital, Fudan University, Shanghai, China. .

Abstract:  Objective: Ischemia hypoxia induces cardiomyocyte (CM) apoptosis in the process of acute myocardial infarction (AMI). It was showed that pro-apoptosis factor BIM participates in regulating tumor cell apoptosis under ischemia or hypoxia condition, while its role in CM apoptosis after AMI is still unclear. It was revealed that miR-24 expression was significantly reduced in myocardial tissue after AMI. Bioinformatics analysis exhibits that miR-24 is targeted to the 3'-UTR of BIM. This study aims to investigate the role of miR-24 in mediating BIM expression and CM apoptosis. Patients and methods: Dual-luciferase assay was used to confirm the targeted regulation between miR-24 and BIM. Cells were cultured under ischemia hypoxia for 12 h after transfection for 48 h. Cell apoptosis was tested by using flow cytometry. The caspase activity was detected by using spectrophotometry. Wistar rats were divided into four groups, including Sham, AMI, AMI + agomir-control, and AMI + agomir-24 groups. Cardiac function was evaluated by using echocardiography. CM apoptosis was determined by using TUNEL. Infarction area was measured by using evans blue staining. MiR-24 targeted suppressed BIM expression. Results: MiR-24 mimic and/or si-BIM transfection significantly declined the BIM expression, inhibited caspase-9 and caspase-3 activities, and reduced cell apoptosis in H9C2 cells. MiR-24 expression was decreased, while BIM levels were up-regulated in myocardium after AMI. Agomir-24 injection down-regulated the BIM expression in myocardium, reduced CM apoptosis, narrowed infarction area, and improved cardiac function in rats. Conclusions: MiR-24 was reduced, whereas BIM was enhanced in the CM after AMI. MiR-24 up-regulation plays a critical role in decreasing BIM expression, reducing CM apoptosis, and improving cardiac function after AMI. 

Retracted: Yes

PubPeer comments:
 Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, u201cMiR-24 alleviates cardiomyocyte apoptosis after myocardial infarction via targeting BIM, by L.-J. Pan, X. Wang, Y. Ling, H. Gong, published in Eur Rev Med Pharmacol Sci 2017; 21 (13): 3088-3097u2013PMID: 28742197u201d has been withdrawn. [The Publisher apologizes for any inconvenience this may cause] . ![file] The paper had been flagged in a Google document as showing [the signs of a papermill provenance] . https: docs.google.com spreadsheets d 1qBqQMXgzxoBd5bTbqdMuapGheupE5bdIopypju417NM edit#gid=0 ,
DOCK8 functions as an adaptor that links TLR-MyD88 signaling to B cell activation
Authors: Lynda Schneider
Isil Barlan
Douglas Golenbock
Sevgi Keles
Arturo Borzutzky
Gerard Lefranc
Mike Recher
Narayanaswamy Ramesh
Michel J Massaad
Erin Janssen
Reuben Ceja
Majed Dasouki
Ghassan Dbaibo
Talal A Chatila
Maria Kanariou
Ingrid Rauter
Waleed Al-Herz
Rima Wakim
Hans D Ochs
Douglas R McDonald
Sachin Baxi
Safa Baris
Halli Benson
Luigi D Notarangelo
Ismail Reisli
Necil Kutukculer
Alessandro Plebani
Katherine A Fitzgerald
Haifa H Jabara
John Manis
Raif S Geha
Journal: Nature Immunology (2012)
Discipline: IMMUNOLOGY
Keywords: DOCK8; MyD88; serological memory; antibody responses; CD27(+) memory B cells
Affiliations: Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

Abstract:  The adaptors DOCK8 and MyD88 have been linked to serological memory. Here we report that DOCK8-deficient patients had impaired antibody responses and considerably fewer CD27(+) memory B cells. B cell proliferation and immunoglobulin production driven by Toll-like receptor 9 (TLR9) were considerably lower in DOCK8-deficient B cells, but those driven by the costimulatory molecule CD40 were not. In contrast, TLR9-driven expression of AICDA (which encodes the cytidine deaminase AID), the immunoglobulin receptor CD23 and the costimulatory molecule CD86 and activation of the transcription factor NF-κB, the kinase p38 and the GTPase Rac1 were intact. DOCK8 associated constitutively with MyD88 and the tyrosine kinase Pyk2 in normal B cells. After ligation of TLR9, DOCK8 became tyrosine-phosphorylated by Pyk2, bound the Src-family kinase Lyn and linked TLR9 to a Src-kinase Syk-transcription factor STAT3 cascade essential for TLR9-driven B cell proliferation and differentiation. Thus, DOCK8 functions as an adaptor in a TLR9-MyD88 signaling pathway in B cells. 

Retracted: No

PubPeer comments:
 Figures 5b and 6d much more similar than expected. ![file] , 
 Figure 7d. Much more similar than expected. ![file] , 
 Author Correction Published: 24 March 2022 Correction to: Nature Immunology https: doi.org 10.1038 ni.2305, published online 13 May 2012. In the version of this article initially published, there was an error in Fig. 7d. The center blot for DOCK8 was an inadvertent duplication of Pyk2, directly above. The correct blot for DOCK8 is shown below and the source data accompanying this figure are available online. ![file] *** ![file] , 
 No mention of Figures 5b and 6d. ,