PReD-Bench/PRed-Bench huggingface dataset:
Emotional Mirror Neurons in the Rat‚Äôs Anterior Cingulate Cortex
Authors: Filippo Migliorati
Maria Carrillo
Christian Keysers
Valeria Gazzola
Yinging Han
Ming Liu
Journal: Current Biology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: causality; emotional contagion; empathy; fear; mirror neurons

Abstract:  How do the emotions of others affect us? The human anterior cingulate cortex (ACC) responds while experiencing pain in the self and witnessing pain in others, but the underlying cellular mechanisms remain poorly understood. Here we show the rat ACC (area 24) contains neurons responding when a rat experiences pain as triggered by a laser and while witnessing another rat receive footshocks. Most of these neurons do not respond to a fear-conditioned sound (CS). Deactivating this region reduces freezing while witnessing footshocks to others but not while hearing the CS. A decoder trained on spike counts while witnessing footshocks to another rat can decode stimulus intensity both while witnessing pain in another and while experiencing the pain first-hand. Mirror-like neurons thus exist in the ACC that encode the pain of others in a code shared with first-hand pain experience. A smaller population of neurons responded to witnessing footshocks to others and while hearing the CS but not while experiencing laser-triggered pain. These differential responses suggest that the ACC may contain channels that map the distress of another animal onto a mosaic of pain- and fear-sensitive channels in the observer. More experiments are necessary to determine whether painfulness and fearfulness in particular or differences in arousal or salience are responsible for these differential responses. 

Retracted: No

PubPeer comments:
 In figure 4, the panels reporting the proportion of trials where the animals are displaying different behaviors appear to be duplicated for the high shock and low shock conditions. ,
Retracted : MicroRNA‚Ä?03 confers the resistance to long‚Äêtreatment of adriamycin to human leukemia cells by regulation of COP1
Authors: Zhuo Peng
Jiangli Sun
Lin Wan
Yanlong Tian
Rui Zhang
Wanggang Zhang
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PI3K/AKT; acute myeloid leukemia; adriamycin; cell proliferation COP1 microRNA-103.
Affiliations: Emergency Department, Hospital of Northwestern Polytechnical University, Xi'an, Shaanxi, China., Department of Pathology, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, Shaanxi, China., Emergency Department, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China., Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Abstract:  Adriamycin (ADR) is an anti-cancer drug which offers improvement in survival for acute myeloid leukemia (AML) patients. However, the drug resistance is almost inevitable. Increasing evidences suggested that microRNAs (miRNAs) were associated with cancer chemo-resistance. Here, we aimed to explore the possible mechanism of miR-103 affected resistance to ADR in AML cells. Different concentrations of ADR were used to induce K562 and KASUMI-1 cells, and miR-103 mimic, inhibitor were transfected into K562 and KASUMI-1 cells. Cell viability and proliferation were determined by trypan blue staining and MTT assays for evaluating K562 and KASUMI-1 cells drug resistance. The relationship of miR-103 and COP1, Trib1, and C/EBPŒ± were analyzed by qRT-PCR and Western blot. Cell proliferation, viability were detected again. Besides, the expressions of main factors of cell cycle and PI3K/AKT signal pathway were analyzed by Western blot. Results showed that ADR inhibited cell viability and proliferation in K562 and KASUMI-1 cells. However, K562 and KASUMI-1 cells appeared drug resistance for 50 passages at 0.8 ¬µM of ADR. In addition, miR-103 expression was up-regulated in ADR-resistant K562 cells (K562/ADR) and overexpression of miR-103 increased K562 cells drug resistance via promoting cell viability and cell cycle-related factors expressions. COP1 was positively regulated by miR-103, suppression of miR-103 recovered K562/ADR cells drug resistance by regulation of COP1, Trib1, and C/EBPŒ±. Besides, miR-103 blocked PI3K/AKT signal pathway by regulation of COP1. These data indicated that miR-103 was up-regulated in drug resistant cells and it may regulate ADR-resistance by regulation of COP1 in AML cells. 

Retracted: Yes

PubPeer comments:
 Has anyone check the correction of the primer sequence in the articleuff1f cause I cant get any of them blasted within NCBI Mus musculus species databaseuff0cboth mitochondria-encoded genes or nuclear-encoded genes. ,
Tenomodulin regulates matrix remodeling of mouse tendon stem/progenitor cells in an ex¬†vivo collagen I gel model
Authors: Zexing Yan
Manuel Delgado Caceres
Denitsa Docheva
Matthias Schieker
Heyong Yin
Michael Nerlich
Journal: Biochemical and Biophysical Research Communications (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Collagen contraction; Collagen type I; Knockout; Tendon; Tenomodulin.
Affiliations: Experimental Trauma Surgery, Department of Trauma Surgery, University Regensburg Medical Centre, Regensburg, Germany; Department of Surgery, Ludwig-Maximilians-University (LMU), Munich, Germany., Experimental Trauma Surgery, Department of Trauma Surgery, University Regensburg Medical Centre, Regensburg, Germany., Department of Surgery, Ludwig-Maximilians-University (LMU), Munich, Germany; Novartis Institutes for Biomedical Research (NIBR), Translational Medicine Musculoskeletal Disease, Basel, Switzerland., Experimental Trauma Surgery, Department of Trauma Surgery, University Regensburg Medical Centre, Regensburg, Germany. Electronic address: .

Abstract:  Tenomodulin (Tnmd) is predominantly expressed in tendon and ligament tissues. Loss of Tnmd in mice leads to a profound phenotype in vitro, characterized by reduced self-renewal but increased senescence of mouse tendon stem/progenitor cells (mTSPCs), as well as in vivo, by significantly impaired early tendon healing. Interestingly, injuried Achilles tendons from Tnmd-deficient mice showed inferior tendon repair, which was characterized by less contracted fibrovascular scars with disorganized matrix composition in comparison to wild type (WT) mice at day 8 after injury. To better understand Tnmd role in tendon repair, here we implemented an ex vivo three-dimensional (3D) collagen gel model and investigated whether Tnmd knockout affects the collagen contraction of mTSPCs. TSPCs were isolated from WT and Tnmd knockout (KO) tendons at 6, 9, 12, and 18 months of age. Adhesion assay demonstrated that loss of Tnmd in mTSPCs resulted in reduced adhesion to collagen type I. Quantitative time-dependent analysis revealed that Tnmd-deficient mTSPCs of all ages have significantly reduced capacity to contract collagen matrix in comparison to WT cells. Furthermore, 18 months old mTSPCs of both genotypes showed lower collagen contractility than cells obtained from 6, 9, and 12 months old animals, demonstrating an overall effect of organismal aging on matrix remodeling. Nevertheless, both cell types had a similar survival rate for the 5 days of cultivation within the gels. Lastly, quantitative PCR for 48 different genes revealed that the knockout of Tnmd majorly affected the gene expression profile of mTSPCs, as several transcription factors, tendon matrix, collagen cross-linking, and lineage maker genes were down-regulated. Taken together, our results clearly demonstrated that loss of Tnmd in mTSPCs led to profoundly altered gene expression profile, insufficient adhesion to collagen type I, and impaired ability to contract the extracellular matrix. 

Retracted: No

PubPeer comments:
 Two images in Figure 3D appear identical to my eye (blue boxes). Could the authors please check? ***  ,
Knockdown of High Mobility Group-Box 3 (HMGB3) Expression Inhibits Proliferation, Reduces Migration, and Affects Chemosensitivity in Gastric Cancer Cells
Authors: Chen Li
Qingjun Wang
Yu Jing
Mingzi Chen
Zhitu Zhu
Lu Hu
Shengnan Guo
Yu Gao
Fangyu Jing
Minghao Xu
Yuanyuan Wang
Yinxu Zhang
Journal: Medical Science Monitor (2016)
Discipline: CLINICAL MEDICINE
Keywords: HMGB3; gastric cancer; cell proliferation; migration; invasion
Affiliations: Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).

Abstract:  BACKGROUND High mobility group-box 3 (HMGB3) has been shown to affect tumor initiation and progression. This research aimed to investigate the role of HMGB3 in gastric cancer (GC) cell proliferation, migration, invasion, chemoresistance, and its potential molecular mechanisms. MATERIAL AND METHODS GC MGC803 and BGC823 cells were transfected with siRNA targeting the HMGB3 gene. The expressions of HMGB3 protein in MGC803 and BGC823 cells after transfection were detected by Western blot assays. We detected cell proliferation and cell cycle by MTT and flow cytometry assay. Cell migration and invasion were determined by wound scratch and transwell assay. MGC803 and BGC823 cells were treated with various concentrations of oxaliplatin, cisplatin, and paclitaxel. After 24 hours of drug exposure, we performed MTT assays to investigate chemoresistance in both groups. Western blot assays were used to detect related proteins expression. RESULTS Silencing of HMGB3 inhibited cell proliferation and induced G0/G1 phase arrest of GC cells partly via modulating p53 and p21 pathways, and downregulating Bcl-2/Bax ratio. RNA interference of HMGB3 inhibited cell invasion and migration by downregulating MMP2 and MMP9. Silencing of HMGB3 enhanced sensitive to cisplatin and paclitaxel, and reduced sensitive to oxaliplatin. CONCLUSIONS These findings suggest the importance of HMGB3 in the regulation of growth, migration, and apoptosis of GC, improve our understanding of the mechanisms of GC pathogenesis, and may promote the development of novel targeted therapies. 

Retracted: No

PubPeer comments:
 Authors should note another well executed study showing that previous reports of 6mA in mammals are artifactual: No evidence for DNA N6-methyladenine in mammals https: advances.sciencemag.org content 6 12 eaay3335  Unfortunately, in the absence of a 6mdA detection technique robust to the multiple sources of error that we have outlined, we conclude that the evidence published to date is not sufficient to support the presence of 6mdA in mammals. ,
LncRNA UCA1 impacts cell proliferation, invasion, and migration of pancreatic cancer through regulating miR-96/FOXO3
Authors: Haixin Qian
Wenzhou Ding
Tu Dai
Liying Wang
Yigang Chen
Zhiyuan Hua
Ye Zhu
Yongping Zhou
Journal: IUBMB life (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: FOXO3; LncRNA UCA1; miR-96; pancreatic cancer.
Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China., Department of Hepatobiliary Surgery, Wuxi Second Hospital, Nanjing Medical University, Wuxi, Jiangsu, China., Department of General Surgery, Wuxi Second Hospital, Nanjing Medical University, Wuxi, Jiangsu, China.

Abstract:  This study was expected to reveal the regulatory effects of lncRNA UCA1 on pancreatic cancer cell progression through targeting miR-96/FOXO3. Microarray analysis was carried out on 36 cases of pancreatic cancer tissues and 16 cases of adjacent tissues among them. Expression levels of lncRNA UCA1, miR-96, and FOXO3 in pancreatic cancer tissues and cell lines were determined by qRT-PCR. Expression levels of FOXO3 protein were determined by western blot. Cell viability, cell cycle and apoptosis, cell invasion and migration were detected by CCK-8, flow cytometry, and transwell assay, respectively. The colocalization relationship between lncRNA UCA1 and miR-96 was detected by RNA FISH. Whether UCA1 could target miR-96 and whether miR-96 could target FOXO3 3'UTR were verified by dual-luciferase reporter gene assay. High expression of lncRNA UCA1 and FOXO3 and low expression of miR-96 were shown in pancreatic cancer. Inhibition of UCA1 suppressed pancreatic tumor cell proliferation, colony formation, and metastasis, while inhibition of miR-96 promoted pancreatic cancer cell progression. FOXO3 was the downstream target gene of miR-96 and showed the opposite effects. LncRNA UCA1 promoted cell proliferation, invasion, migration and inhibited cell apoptosis of pancreatic cancer through down-regulating miR-96 and up-regulating FOXO3. ¬© 2018 IUBMB Life, 70(4):276-290, 2018. 

Retracted: No

PubPeer comments:
 Figures 3C,D and 7A,B. Some panels reappear. Could the authors clarify whether they represent invasion or migration assays, and whether they were the results of some treatment or a negative control?  ,
Rapid birth-and-death evolution of imprinted snoRNAs in the Prader-Willi syndrome locus: implications for neural development in Euarchontoglires
Authors: Hui Zhang
Jun Liu
Yi-Jun Zhang
Ling-Ling Zheng
Liang-Hu Qu
Qiao-Su Shi
Hui Zhou
Jian-Hua Yang
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Imprinted snoRNAs; Prader-Willi syndrome; Evolution; Gene gain; Gene loss
Affiliations: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, and School of Life Sciences, Sun Yat-sen University, Guangzhou, P. R. China., Laboratory of Liver Disease Hospital, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China., Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, P. R. China.

Abstract:  Imprinted small nucleolar RNAs (snoRNAs) are only found in eutherian genomes and closely related to brain functions. A complex human neurological disease, Prader-Willi syndrome (PWS), is primarily attributed to the deletion of imprinted snoRNAs in chromosome 15q11-q13. Here we investigated the snoRNA repertoires in the PWS locus of 12 mammalian genomes and their evolution processes. A total of 613 imprinted snoRNAs were identified in the PWS homologous loci and the gene number was highly variable across lineages, with a peak in Euarchontoglires. Lineage-specific gene gain and loss events account for most extant genes of the HBII-52 (SNORD115) and the HBII-85 (SNORD116) gene family, and remarkable high gene-birth rates were observed in the primates and the rodents. Meanwhile, rapid sequence substitution occurred only in imprinted snoRNA genes, rather than their flanking sequences or the protein-coding genes located in the same imprinted locus. Strong selective constraints on the functional elements of these imprinted snoRNAs further suggest that they are subjected to birth-and-death evolution. Our data suggest that the regulatory role of HBII-52 on 5-HT2CR pre-mRNA might originate in the Euarchontoglires through adaptive process. We propose that the rapid evolution of PWS-related imprinted snoRNAs has contributed to the neural development of Euarchontoglires. 

Retracted: No

PubPeer comments:
 Tajima s D test is normally used to test for evolutive contraints on a DNA sequence by analyzing population samples. Here it is used to test paralogous sequences of a large array of repeated genes. There are no population variants analyzed. I wonder whether such an extrapolation of the Tajima s D test is correct. ,
The impact of metformin and salinomycin on transforming growth factor Œ≤-induced epithelial-to-mesenchymal transition in non-small cell lung cancer cell lines
Authors: Stefan Koeck
Arno Amann
Julia M Huber
Heinz Zwierzina
Wolfgang Hilbe
Gabriele Gamerith
Journal: Oncology Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: epithelial marker; epithelial-to-mesenchymal transition; metformin; migration; non-small cell lung cancer
Affiliations: Department of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol 6020, Austria., Department of Internal Medicine V, Medical University of Innsbruck, Innsbruck, Tyrol 6020, Austria; Department of Internal Medicine I, Wilhelminenspital, Vienna 1160, Austria.

Abstract:  The epithelial-to-mesenchymal transition (EMT) is highly involved in the development of metastases. EMT transforms epithelial carcinoma cells into mesenchymal-like cells, characterized by increased cell migration and invasiveness. Transforming growth factor Œ≤ (TGFŒ≤) appears to be crucial in this process. Metformin and salinomycin have demonstrated an EMT inhibitory effect. The current experiments indicate that these substances specifically inhibit TGFŒ≤-induced EMT in non-small cell lung cancer (NSCLC) cell lines. The NSCLC cell lines A549 and HCC4006 were stimulated with TGFŒ≤ for 48 h to induce EMT. Metformin or salinomycin was added simultaneously with TGFŒ≤ to inhibit TGFŒ≤-induced EMT. Western blot analyses of E-cadherin and vimentin were performed to detect changes in EMT marker expression, and a wound healing assay was conducted to determine the potential effects on cell migration. The effects of the two drugs on cell viability were also investigated using MTS tetrazolium dye assays. The results revealed that cells undergoing EMT by application of TGFŒ≤ exhibited a downregulation of E-cadherin and an upregulation of vimentin protein expression on western blot analyses, and an increased capacity for cell migration. Simultaneous application of TGFŒ≤ and metformin specifically inhibited EMT and increased E-cadherin expression. At the higher dose tested, salinomycin also inhibited EMT, despite an increase in vimentin expression in the two cell lines. Furthermore, metformin and salinomycin, at the two concentrations tested, inhibited cell migration. These findings demonstrate that metformin and salinomycin are able to block EMT and inhibit EMT-induced cell migration. Thus, these two substances are novel EMT inhibiting drugs that have the potential to specifically control EMT and metastatic spread in NSCLC. 

Retracted: No

PubPeer comments:
 Figure 3. The bottom two panels (- and + TGGb) appear to show the same cells but with a different layer of edge tracking.  ,
Tyrosine phosphorylation of the beta 4 integrin cytoplasmic domain mediates Shc signaling to extracellular signal-regulated kinase and antagonizes formation of hemidesmosomes
Authors: P Blaikie
F G Giancotti
A Mariotti
M Dans
S Klein
L Gagnoux-Palacios
Journal: Journal of Biological Chemistry (2001)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: alpha(6)beta(4) integrin; tyrosine phosphorylation; beta(4) cytoplasmic domain; Shc; mitogen-activated protein kinase cascades
Affiliations: Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

Abstract:  Ligation of the alpha(6)beta(4) integrin induces tyrosine phosphorylation of the beta(4) cytoplasmic domain, followed by recruitment of the adaptor protein Shc and activation of mitogen-activated protein kinase cascades. We have used Far Western analysis and phosphopeptide competition assays to map the sites in the cytoplasmic domain of beta(4) that are required for interaction with Shc. Our results indicate that, upon phosphorylation, Tyr(1440), or secondarily Tyr(1422), interacts with the SH2 domain of Shc, whereas Tyr(1526), or secondarily Tyr(1642), interacts with its phosphotyrosine binding (PTB) domain. An inactivating mutation in the PTB domain of Shc, but not one in its SH2 domain, suppresses the activation of Shc by alpha(6)beta(4). In addition, mutation of beta(4) Tyr(1526), which binds to the PTB domain of Shc, but not of Tyr(1422) and Tyr(1440), which interact with its SH2 domain, abolishes the activation of ERK by alpha(6)beta(4). Phenylalanine substitution of the beta(4) tyrosines able to interact with the SH2 or PTB domain of Shc does not affect incorporation of alpha(6)beta(4) in the hemidesmosomes of 804G cells. Exposure to the tyrosine phosphatase inhibitor orthovanadate increases tyrosine phosphorylation of beta4 and disrupts the hemidesmosomes of 804G cells expressing recombinant wild type beta(4). This treatment, however, exerts a decreasing degree of inhibition on the hemidesmosomes of cells expressing versions of beta(4) containing phenylalanine substitutions at Tyr(1422) and Tyr(1440), at Tyr(1526) and Tyr(1642), or at all four tyrosine phosphorylation sites. These results suggest that beta(4) Tyr(1526) interacts in a phosphorylation-dependent manner with the PTB domain of Shc. This event is required for subsequent tyrosine phosphorylation of Shc and signaling to ERK but not formation of hemidesmosomes. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar than you would expect. https: imgur.com Cv0NaZY , 
 Figure 4A. Much more simialr than you would expect after horizontal flipping. https: imgur.com IELqMJK ,
Down-regulation of Shadoo in prion infections traces a pre-clinical event inversely related to PrP(Sc) accumulation
Authors: Janaky Coomaraswamy
Agnes Lau
Inyoul Lee
Jing Yang
Charles E Mays
Rose Pitstick
Gerold Schmitt-Ulms
Nathalie Daude
Sacha Genovesi
Allen Herbst
Brenda Canine
George A Carlson
Leroy Hood
Stephen J Dearmond
Kerry W S Ko
Debbie McKenzie
David Westaway
Rebecca Brown
Journal: PLoS Pathogens (2011)
Discipline: MICROBIOLOGY
Keywords: prion infections; central nervous system; PrP(C); PrP(Sc); Sprn gene
Affiliations: Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada.

Abstract:  During prion infections of the central nervous system (CNS) the cellular prion protein, PrP(C), is templated to a conformationally distinct form, PrP(Sc). Recent studies have demonstrated that the Sprn gene encodes a GPI-linked glycoprotein Shadoo (Sho), which localizes to a similar membrane environment as PrP(C) and is reduced in the brains of rodents with terminal prion disease. Here, analyses of prion-infected mice revealed that down-regulation of Sho protein was not related to Sprn mRNA abundance at any stage in prion infection. Down-regulation was robust upon propagation of a variety of prion strains in Prnp(a) and Prnp(b) mice, with the exception of the mouse-adapted BSE strain 301 V. In addition, Sho encoded by a TgSprn transgene was down-regulated to the same extent as endogenous Sho. Reduced Sho levels were not seen in a tauopathy, in chemically induced spongiform degeneration or in transgenic mice expressing the extracellular ADan amyloid peptide of familial Danish dementia. Insofar as prion-infected Prnp hemizygous mice exhibited accumulation of PrP(Sc) and down-regulation of Sho hundreds of days prior to onset of neurologic symptoms, Sho depletion can be excluded as an important trigger for clinical disease or as a simple consequence of neuronal damage. These studies instead define a disease-specific effect, and we hypothesize that membrane-associated Sho comprises a bystander substrate for processes degrading PrP(Sc). Thus, while protease-resistant PrP detected by in vitro digestion allows post mortem diagnosis, decreased levels of endogenous Sho may trace an early response to PrP(Sc) accumulation that operates in the CNS in vivo. This cellular response may offer new insights into the homeostatic mechanisms involved in detection and clearance of the misfolded proteins that drive prion disease pathogenesis. 

Retracted: No

PubPeer comments:
 Identified by another reader. ***  , 
 Another look at 2a. ***  ,
Two types of asynchronous activity in networks of excitatory and inhibitory spiking neurons
Authors: Srdjan Ostojic
Journal: Nature Neuroscience (2014)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Asynchronous activity; balanced networks; excitatory neurons; inhibitory neurons; spiking neurons
Affiliations: Group for Neural Theory, Laboratoire de Neurosciences Cognitives, INSERM U960, √âcole Normale Sup√©rieure, Paris, France.

Abstract:  Asynchronous activity in balanced networks of excitatory and inhibitory neurons is believed to constitute the primary medium for the propagation and transformation of information in the neocortex. Here we show that an unstructured, sparsely connected network of model spiking neurons can display two fundamentally different types of asynchronous activity that imply vastly different computational properties. For weak synaptic couplings, the network at rest is in the well-studied asynchronous state, in which individual neurons fire irregularly at constant rates. In this state, an external input leads to a highly redundant response of different neurons that favors information transmission but hinders more complex computations. For strong couplings, we find that the network at rest displays rich internal dynamics, in which the firing rates of individual neurons fluctuate strongly in time and across neurons. In this regime, the internal dynamics interact with incoming stimuli to provide a substrate for complex information processing and learning. 

Retracted: No

PubPeer comments:
 Readers should become aware of a preprint that calls into question part of the conclusions of this study entitled:  Comment on u201cTwo types of asynchronous activity in networks of excitatory and inhibitory spiking neuronsu201d https: www.biorxiv.org content 10.1101 017798v1 And the author s reply: Response to Comment on u201cTwo types of asynchronous activity in networks of excitatory and inhibitory spiking neuronsu201d https: www.biorxiv.org content 10.1101 020354v1 , 
 A follow-up study addressed the remaining issues in more detail: https: journals.plos.org ploscompbiol article?id=10.1371 journal.pcbi.1005498 ,
The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells
Authors: Apurva Sarin
Hadassah Sade
Sudhir Krishna
Journal: Journal of Biological Chemistry (2004)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Notch family; anti-apoptotic function; T cells; AcN1; inhibitors of apoptosis
Affiliations: National Centre for Biological Sciences, University of Agricultural Sciences-Gandhi Krishi Vignan Kendra Campus, New Bellary Road, Bangalore 560065, Karnataka, India.

Abstract:  The Notch family of transmembrane receptors have been implicated in a variety of cellular decisions in different cell types. Here we investigate the mechanism underlying Notch-1-mediated anti-apoptotic function in T cells using model cell lines as the experimental system. Ectopic expression of the intracellular domain of Notch-1/activated Notch (AcN1) increases expression of anti-apoptotic proteins of the inhibitors of apoptosis (IAP) family, the Bcl-2 family, and the FLICE-like inhibitor protein (FLIP) and inhibits death triggered by multiple stimuli that activate intrinsic or extrinsic pathways of apoptosis in human and murine T cell lines. Numb inhibited the AcN1-dependent induction of anti-apoptotic proteins and anti-apoptotic function. Using pharmacological inhibitors and dominant-negative approaches, we describe a functional role for phosphatidylinositol 3-kinase (PI3K)-dependent activation of the serine-threonine kinase Akt/PKB in the regulation of AcN1-mediated anti-apoptotic function and the expression of FLIP and IAP family proteins. Using a cell line deficient for the T cell-specific, Src family protein, the tyrosine kinase p56(lck) and by reconstitution approaches we demonstrate that p56(lck) is required for the Notch-1-mediated activation of Akt/PKB function. Furthermore, the Src tyrosine kinase inhibitor, PP2, abrogated ectopically expressed AcN1-mediated anti-apoptotic function and phosphorylation of p56(lck). We present evidence that endogenous Notch-1 associates with p56(lck) and PI3K but that Akt/PKB does not co-immunoprecipitate with the Notch1.p56(lck).PI3K complex. Finally, we demonstrate that the Notch1.p56(lck).PI3K complex is present in primary T cells that have been activated in vitro and sustained in culture with the cytokine interleukin-2. 

Retracted: No

PubPeer comments:
 Figure 5A. https: imgur.com amUB1BL , 
 The lower blot is a strip and re-probe of the membrane and inhomogeneity s during processing have contributed artefacts. Other imperfections are also apparent in the blot. ,
MiR-370 functions as oncogene in melanoma by direct targeting pyruvate dehydrogenase B
Authors: Shufang Wei
Weiyuan Ma
Journal: Biomedicine & Pharmacotherapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Melanoma; MiR-370; PDHB.
Affiliations: Department of Dermatology, Qilu Hospital of Shandong University, China., Department of Dermatology, Qilu Hospital of Shandong University, China. Electronic address: .

Abstract:  Background: Accumulating evidence has shown that miR-370 play an important role in the development and progression of tumor. However, the role of miR-370 in melanoma remains largely unknown. The present study is designed to investigate the function of miR-370 in melanoma and to explore the molecular mechanism underlying its function. Materials and methods: The expression level of miR-370 was detected in melanoma tissues and cell lines by real-time quantitative polymerase chain reaction (qRT-PCR). The effect of overexpression of miR-370 on in vitro cell proliferation, apoptosis, invasion as well as glyclolysis was examined. Western blotting analysis was used to detect the influence of miR-370 on the expression of target genes, and Pearson analysis was used to calculate the correlation between the expression of targets gene and miR-370 in melanoma tissues. Results: Our study showed that miR-370 was upregulated in melanoma tissues compared with non-cancerous tissues (P&lt;0.01). In addition, the expression of miR-370 in melanoma cell lines was also significantly higher (P&lt;0.01). Enforced expression of miR-370 promotes melanoma cell proliferation, inhibits apoptosis and enhances invasion and glycolysis and led to downregulation of the PDHB protein. Moreover, the expression level of miR-370 in melanoma tissues showed inverse relationship with the expression level of PDHB protein. Conclusions: In conclusion, our findings suggested that miR-370 represents a potential oncogenic miRNA and plays an important role in melanoma progression by directly targeting PDHB. 

Retracted: No

PubPeer comments:
 Figure 3B. * Marked with red boxes: In the  200 uM row, the 0h and 36h panels appear to look similar to each other. Could the authors please check?  ,
Rubriflordilactones A and B, two novel bisnortriterpenoids from Schisandra rubriflora and their biological activities
Authors: Xiao-Li Li
Jian-Xin Pu
Li Wu
Yong-Tang Zheng
Yang Lu
Rui-Rui Wang
Han-Dong Sun
Ning-Bo Gong
Rong-Tao Li
Qi-Tai Zheng
Liu-Meng Yang
Wei-Lie Xiao
Sheng-Xiong Huang
Journal: Organic Letters (2006)
Discipline: CHEMISTRY
Keywords: Rubriflordilactones; bisnortriterpenoids; Schisandra rubriflora; spectroscopic methods; NMR techniques
Affiliations: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, Yunnan, P. R. China.

Abstract:  Rubriflordilactones A (1) and B (2), two novel highly unsaturated rearranged bisnortriterpenoids possessing a biosynthetically modified aromatic D-ring, were isolated from the leaves and stems of Schisandra rubriflora. Their structures were established on the basis of extensive spectroscopic methods, including two-dimensional NMR techniques, and confirmed by X-ray crystallographic analysis. Compound 1 showed weak anti-HIV-1 activity, and compound 2 exhibited an EC50 value of 9.75 microg/mL (SI=12.39) against HIV-1 replication with low cytotoxicity. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Supplemental materials, page 4: The HMQC spectrum of rubriflordilactone A (1) shows some unexpected discontinuities. Here is the full figure:  Some details from the top (horizontal) spectrum, from left to right, with some unexpected gaps or double lines:      Could the authors please comment on these unexpected gaps and cut-off tops, and double lines? , 
 The graph shown on Figure 8 of the supplemental material shows similar cut-off tops, gaps, and double lines. First, here is the overview:  Here are some details of that Figure. I have added some red arrows to point out unexpected discontinuities.      Could the authors please comment on these unexpected gaps and cut-off tops, and double lines? , 
 The figure on page 9 has a repetitive group of peaks that pop ups every and then, as well as tops that appear to have been cutoff around the 170 marker.  , 
 If you open the PDF in a vector editting program such as Adobe illustrator or GIMP you can actually delete the white boxes that they have added to figure 8 , 
 SI page 13, opened with Illustrator:  Once you remove the white rectangles, there are other peaks below:  , 
 Correction, March 2021: https: pubs.acs.org doi 10.1021 acs.orglett.1c00700  *In 2006, we reported two novel bisnortriterpenoids isolated from Schisandra rubriflora, rubriflordilactones A (1) and B (2), and these two structures were all determined by X-ray crystallography. Solvent and or impurity peaks had been removed from the 1H and 13C NMR spectra reported for compounds 1 and 2. The original spectra have been replaced for the above compounds in the revised Supporting Information submitted with this correction. The spectral editing did not affect any of the conclusions of the published paper.* ,
Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT
Authors: Yiyang Jiang
Thomas L Benz
Stephen B Long
Journal: Science (2021)
Discipline: Multidisciplinary
Keywords: Hedgehog proteins; developmental steps; human cancers; cryo-electron microscopy; HHAT
Affiliations: Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Abstract:  Hedgehog proteins govern crucial developmental steps in animals and drive certain human cancers. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino-terminal palmitoylation by Hedgehog acyltransferase (HHAT). We present cryo-electron microscopy structures of human HHAT in complex with its palmitoyl-coenzyme A substrate and of a product complex with a palmitoylated Hedgehog peptide at resolutions of 2.7 and 3.2 angstroms, respectively. The structures reveal how HHAT overcomes the challenges of bringing together substrates that have different physiochemical properties from opposite sides of the endoplasmic reticulum membrane within a membrane-embedded active site for catalysis. These principles are relevant to related enzymes that catalyze the acylation of Wnt and of the appetite-stimulating hormone ghrelin. The structural and mechanistic insights may advance the development of inhibitors for cancer. 

Retracted: No

PubPeer comments:
 Retracted [1 December 2016](http: www.funpecrp.com.br gmr year2016 vol15-4 pdf gmr-15-04-gmr.1504005.pdf). --------------------------------- The GMR editorial staff was alerted about some articles that were found to be substantially equal. After a thorough investigation and contacting the authors, the Publisher and Editor of Genetics and Molecular Research decided to retract these articles in accordance with the recommendations of the Committee on Publication Ethics (COPE). The authors and their institutions were advised of this serious breach of ethics. [...] These articles contain portions of the text that are similar to each other and to manuscripts that had already been published. All figures, along with their legends, are likely the same and or modified from studies already published and from the abovementioned papers published by GMR. The studies, from where the texts and figures were substantially copied, are: - Gong Y, Ren J, Liu K and Tang LM (2015). [Tumor suppressor role of miR-133a in gastric cancer by repressing IGF1R] . World J. Gastroenterol. 21 (10): 2949-2958. DOI: 10.3748 wjg.v21.i10.2949 - Hou Y, Zhen J, Xu X, Zhen K, et al. (2015). [miR-215 functions as a tumor suppressor and directly targets ZEB2 in human non-small lung cancer] . Oncol. Lett. 10 (4): 1985-1992 - Liu X, Yan S, Pei C and Cui Y (2015). [Decreased miR-132 function in human non-small non-small cell lung cancer] . Mol. Med. Rep. 11 (5): 3601-3608. DOI: 10.3892 mmr.2015.3222. ----------------------------------- ,
Photocatalytic Reduction of Fluorescent Dyes in Sunlight by Newly Synthesized Spiroindenoquinoxaline Pyrrolizidines
Authors: Man Singh
Renu Kumari
Journal: ACS Omega (2020)
Discipline: CHEMISTRY
Keywords: Spiroindenoquinoxaline pyrrolizidines; cascade Knoevenagel condensation; photocatalyzed; fluorescent dyes; photonic sensor
Affiliations: School of Chemical Sciences, Central University of Gujarat, Gandhinagar 382030, India

Abstract:  Spiroindenoquinoxaline pyrrolizidines (SIQPs)-7-nitro-2'-phenyl-5',6',7',7a'-tetrahydrospiro[indeno[1,2-b]quinoxaline-11,3'-pyrrolizine]-1',1'(2'H)-dicarbonitrile (SIQP I), 2'-(4-cyanophenyl)-7-nitro-5',6',7',7a'-tetrahydrospiro[indeno[1,2-b]quinoxaline-11,3'-pyrrolizine]-1',1'(2'H)-dicarbonitrile (SIQP II), and 2'-(4-methoxyphenyl)-7-nitro-5',6',7',7a'-tetrahydrospiro[indeno[1,2-b]quinoxaline-11,3'-pyrrolizine]-1',1'(2'H)-dicarbonitrile (SIQP III)-have been synthesized through a one-pot cascade Knoevenagel condensation reaction in acetonitrile (ACN) with 91, 98, and 87% yields, respectively. Structures are characterized by 1H NMR and 13C NMR spectroscopy, nuclear Overhauser enhancement spectroscopy (NOESY), Fourier transform infrared (FT-IR) and UV-vis spectroscopy, thermogravimetric analysis (TGA), high-resolution mass spectroscopy (HRTEM), fluorescence and Raman spectroscopy, and energy-dispersive analysis by X-ray (EDX) spectroscopy. SIQPs in ACN photocatalyzed methylene blue (MB) but not phenolphthalein (HIn). SIQPs distinguished the quaternary atoms and dipoles of the fluorescent dye (MB) contrary to the quinonoid HIn structure. In sunlight, SIQPs without electricity input acted as a photonic sensor to detect fluorescent dyes in waste effluents of textile, paper, dyes, and other industries. Activation energy (E a), enthalpy (ŒîH), entropy (ŒîS), and Gibbs free energy (ŒîG) calculated from UV-vis absorption spectra show photocatalytic reduction (PCR) activities in the order SIQP II &gt; III &gt; I. The N-atom of pyrrolizidine and -NO2 of nitro-indenoquinoxaline (NIQ) induced the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO) electrodynamics to enable the SIQPs to catalyze biochemical activities. 

Retracted: No

PubPeer comments:
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 Once we had a similar problem with our IR. The detector was changed and the problem was resolved. Possibly, they have a detector problem in their device. , 
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 The Supporting Information file in the original manuscript had errors. The revised Supporting Information is given here [](http: )https: pubs.acs.org doi 10.1021 acsomega.0c05835 , 
 Correction to this research article - https: pubs.acs.org doi 10.1021 acsomega.0c05835 ,
One-Pot Catalytic Cleavage of C‚ïêS Double Bonds by Pd Catalysts at Room Temperature
Authors: Wang Xing
Ting Zhu
Hui Huang
Xiaoxi Wu
Jiaming Huang
Bigyan Sharma
Zhenwen Zhao
Wentao Wang
Xinzheng Yang
Na Li
Journal: Inorganic Chemistry (2018)
Discipline: CHEMISTRY
Keywords: CS2; thioketones; Pd dimeric complexes; catalytic cleavage; CO2

Abstract:  The C‚ïêS double bonds in CS2 and thioketones were catalytically cleaved by Pd dimeric complexes [(N‚àßN)2Pd2(NO3)2](NO3)2 (N‚àßN, 2,2'-bipyridine, 4,4'-dimethylbipyridine or 4,4'-bis(trifluoromethyl)) at room temperature in one pot to afford CO2 and ketones, respectively, for the first time. The mechanisms were fully investigated by kinetic NMR, isotope-labeled experiments, in situ ESI-MS, and DFT calculations. The reaction is involved a hydrolytic desulfurization process to generate C‚ïêO double bonds and a trinuclear cluster, which plays a pivotal role in the catalytic cycle to regenerate the dimeric catalysts with HNO3. Furthermore, the electronic properties of catalyst ligands possess significant influence on reaction rates and kinetic parameters. At the same temperature, the reaction rate is consistent with the order of electronegativity of N‚àßN ligands (4,4'-bis(trifluoromethyl) &gt; 2,2'-bipyridine &gt; 4,4'-dimethylbipyridine). This homogeneous catalytic reaction features mild conditions, a broad substrate scope, and operational simplicity, affording insight into the mechanism of catalytic activation of carbon sulfur bonds. 

Retracted: No

PubPeer comments:
 Discrepancies were found in the reported analytical data of 9-fluorenthione. The product is described as a red solid. All other publications reporting the synthesis of this thioketone describe this compound as a green solid, e.g. Mloston et al., Eur. J. Org. Chem. 1998, 459-465 or Scheibye et al. Tetrahedron, 1982, 38, 993-1001. The 1H NMR reported in this manuscript (the only one available in the literature for 9-fluorenthione) fits very well with that of tetrabenzo[5.5]fulvalene, which is known to be a red solid, e.g. see Guan et al., Angew. Chem. Int. Ed., 2020, 59, 14903-14909. I do believe that the authors made tetrabenzo[5.5]fulvalene instead of 9-fluorenthione. Furthermore, this paper discloses the catalytic cleavage of a C=S bond to form the corresponding C=O bond using a palladium dimer. In this paper, 9-fluorenone, the product of the reaction with the previously discussed starting material, is reported to be a white solid, while it is well known that fluorenone is bright yellow. Furthermore, the reported 1H NMR spectrum does not fit with the literature values for 9-fluorenone, e. g. Seo et al., Org. Lett., 2012, 14, 2650-2653. The attached 1H NMR spectrum is unfortunately not of good enough quality to judge whether 9-fluorenone was actually isolated. The lack of 13C NMR spectrum for any compound reported here overall makes the data reported in this manuscript unreliable. ,
RETRACTED ARTICLE: Amelioration of obsessive-compulsive disorder in three mouse models treated with one epigenetic drug: unraveling the underlying mechanism
Authors: Catarina Cunha
David Ashurov
Karthikeyan Mayilvahanan
German Todorov
Journal: Scientific Reports (2019)
Discipline: Multidisciplinary
Keywords: Mental health disorders; epigenetics; anxiety; avoidant behaviors; obsessive compulsive disorders (OCD)
Affiliations: Emotional Brain Institute, Nathan Kline Institute, Orangeburg, NY, USA., Department of Neurobiology and Behavior, Stony Brook University School of Medicine, Stony Brook, NY, USA., Emotional Brain Institute, Nathan Kline Institute, Orangeburg, NY, USA. .

Abstract:  Mental health disorders are manifested in families, yet cannot be fully explained by classical Mendelian genetics. Changes in gene expression via epigenetics present a plausible mechanism. Anxiety often leads to avoidant behaviors which upon repetition may become habitual, maladaptive and resistant to extinction as observed in obsessive compulsive disorders (OCD). Psychophysical models of OCD propose that anxiety (amygdala) and habits (dorsolateral striatum, DLS) may be causally linked. The amygdala activates spiny projection neurons in the DLS. Repetitive amygdala terminal stimulation in the DLS elicits long term OCD-like behavior in mice associated with circuitry changes and gene methylation-mediated decrease in the activity of protein phosphatase 1 (PP1). Treatment of OCD-like grooming behavior in Slitrk5, SAPAP3, and laser-stimulated mice with one dose of RG108 (DNA methyltransferase inhibitor), lead to marked symptom improvement lasting for at least one week as well as complete reversal of anomalous changes in circuitry and PP1 gene methylation. 

Retracted: Yes

PubPeer comments:
 Retraction of: Scientific Reports https: doi.org 10.1038 s41598-019-45325-6, publisher online 19 June 2019 The Editors have retracted this Article. An investigation by the Research Integrity Office at Stony Brook University has concluded that: some of the methodological and experimental descriptions in the paper show significant overlap with NIH grant application R01-NS104089, NARSAD grant application 23840, and a previously published article by Plotkin et al.1; the Authors incorrectly reported results for Slitrk5 knockout mice. Due to problems with genotyping of these animals, the genetic identity of the individual animals was impossible to determine; the Authors incorrectly reported results for Sapap3 knockout mice. The animals used in these experiments were Sapap3 conditional knock-in mice; the experimental conditions in the behavioural tests were also incorrectly reported: the experimenters were not blind to experimental conditions as reported in the paper. The Editors therefore no longer have confidence in the integrity of the data presented in this Article. Catarina Cunha disagrees with the retraction. German Todorov, Karthikeyan Mayilvahanan and David Ashurov did not respond to the correspondence about this retraction. ,
Abrogated RANKL expression in properdin-deficient mice is associated with better outcome from collagen-antibody-induced arthritis
Authors: Cordula Stover
Petya Dimitrova
Lyudmila Belenska
Viktoriya Milanova
Wilhelm Schwaeble
Nina Ivanovska
Journal: Arthritis Research & Therapy (2012)
Discipline: CLINICAL MEDICINE
Keywords: Properdin; collagen antibody-induced arthritis; C5a; RANKL; neutrophils

Abstract:  Introduction: Properdin amplifies the alternative pathway of complement activation. In the present study, we evaluated its role in the development of collagen antibody-induced arthritis (CAIA). Methods: Arthritis was induced by intraperitoneal injection of a collagen antibody cocktail into properdin-deficient (KO) and wild-type (WT) C57BL/6 mice. Symptoms of disease were evaluated daily. The degree of joint damage was assessed histologically and with immunostaining for bone-resorption markers. Phenotypes of cell populations, their receptor expression, and intracellular cytokine production were determined with flow cytometry. Osteoclast differentiation of bone marrow (BM) precursors was evaluated by staining for tartrate-resistant acid phosphatase (TRAP). Results: Properdin-deficient mice developed less severe CAIA than did WT mice. They showed significantly improved clinical scores and downregulated expression of bone-resorption markers in the joints at day 10 of disease. The frequencies of Ly6G‚Å∫CD11b‚Å?cells were fewer in BM, blood, and synovial fluid (SF) of KO than of WT CAIA mice. The receptor activator of nuclear factor Œ∫B ligand (RANKL) was downregulated on arthritic KO neutrophils from BM and the periphery. Decreased C5a amounts in KO SF contributed to lower frequencies of CD5aR‚Å?bearing neutrophils. In blood, surface C5aR was detected on KO Ly6G‚Å?cells as a result of low receptor engagement. Circulating CD4‚Å?T cells had an altered ability to produce interleukin (IL)-17 and interferon (IFN)-Œ≥ and to express RANKL. In KO CAIA mice, decreased frequencies of CD4‚Å?T cells in the spleen were related to low CD86 expression on Ly6GhighCD11b‚Å?cells. Arthritic KO T cells spontaneously secreted IFN-Œ≥ but not IL-17 and IL-6, and responded to restimulation with less-vigorous cytokine production in comparison to WT cells. Fewer TRAP-positive mature osteoclasts were found in KO BM cell cultures. Conclusions: Our data show that the active involvement of properdin in arthritis is related to an increased proinflammatory cytokine production and RANKL expression on immune cells and to a stimulation of the RANKL-dependent osteoclast differentiation. 

Retracted: No

PubPeer comments:
 Figure 5A and 5B appear to have one image which overlaps, at different magnification, but seem to be described differently. Could the authors please check? ***   , 
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