PReD-Bench/PRed-Bench huggingface dataset:
Cyclin-dependent kinase 4/6 activity is a critical determinant of pre-replication complex assembly
Authors: A K McClendon
W A Braden
E S Knudsen
Journal: Oncogene (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CDK4/6; DNA replication; pre-replication complex; cdc6; cdt1
Affiliations: Department of Cancer Biology and the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Abstract:  Cyclin-dependent kinases (CDKs) are important in regulating cell cycle transitions, particularly in coordinating DNA replication. Although the role of CDK2 activity on the replication apparatus has been extensively studied, the role of CDK4/6 in DNA replication control is less understood. Through targeted inhibition of CDK4/6 activity, we demonstrate that CDK4/6 kinase activity promotes cdc6 and cdt1 expression, and pre-replication complex (pre-RC) assembly in cycling cells. Conversely, CDK2 inhibition had no effect on the pre-RC assembly. The inhibition of pre-RC assembly is dependent on a functional retinoblastoma (RB) protein, which mediates downstream effects. As such, CDK4/6 inhibition has minimal effect on the replication apparatus in the absence of RB. The requirement of CDK4/6 was further interrogated using cells lacking D-type cyclins, in which replication complexes form normally, and correspondingly CDK4/6 inhibition had no effect on cell cycle or replication control. However, in the absence of D-type cyclins, CDK2 inhibition resulted in the attenuation of cdc6 and cdt1 levels, suggesting overlapping roles for CDK4/6 and CDK2 in regulating replication protein activity. Finally, CDK4/6 inhibition prevented the accumulation of cdc6 and cdt1 as cells progressed from mitosis through the subsequent G(1). Combined, these studies indicate that CDK4/6 activity is important in regulating the expression of these critical mediators of DNA replication. 

Retracted: No

PubPeer comments:
 Figure 5a. Much more similar than you would expect. https: imgur.com kSZoUsF , 
 Figure 5b. Much more similar than you would expect. https: imgur.com f0QchKa , 
 Figure 5a. Much more similar than you would expect. https: imgur.com Z8FlC5u , 
 Figure 5b. Much more similar than expected. https: imgur.com KELQ3Oy , 
 Thank you for pointing these out--and sorry for the delay in responding. This issue tracks with the MCB 2006 manuscript (which was retracted). I am in contact with Oncogene to make sure this is appropriately resolved. ,
Study on Brain Electromyography Rehabilitation System Based on Data Fusion and Virtual Rehabilitation Simulation
Authors: Shuxia Li
Juncheng Yang
Journal: Journal of Medical Systems (2019)
Discipline: CLINICAL MEDICINE
Keywords: Data fusion; EEG data; EMG data; Rehabilitation system; Virtual prototyping technology.
Affiliations: School of Electronic and Information Engineering, Henan Polytechnic Institute, Zhengzhou, China., School of Electronic and Information Engineering, Henan Polytechnic Institute, Zhengzhou, China. .

Abstract:  In this paper, a virtual rehabilitation training system based on electroencephalogram (EMG) feedback is proposed to solve the problem that the existing virtual rehabilitation training methods can not reflect the initiative of patients and lack of individual adaptability. Aiming at the EEG data fusion rehabilitation system based on Virtual Prototyping technology, a motion pattern recognition method based on the feature fusion of EEG and EMG signals is studied to improve the accuracy and flexibility of the rehabilitation training system. The corresponding virtual rehabilitation training scene is designed, and the control and feedback adjustment of the virtual scene are realized by using the above EEG feature analysis method. Finally, the virtual rehabilitation training is realized. The multi-level coupling relationship between EEG and EMG signals under different grip forces was explored by using the synchronous coupling characteristics between EEG and EMG signals, which provided a theoretical basis for further application in clinical rehabilitation evaluation. 

Retracted: No

PubPeer comments:
 Some papers cited are irrelevant and associated with Shaofei Wu. ![file] ![file] ![file] ![file] ,
Blockade of the insulin-like growth factor I receptor in the choroid plexus originates Alzheimer's-like neuropathology in rodents: new cues into the human disease?
Authors: Delphine Bohl
Carlos Spuch
Jean Michel Heard
Jose Luis Trejo
Ignacio Torres-Aleman
Eva Carro
Journal: Neurobiology of aging (2006)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: insulin; IGF-I; Alzheimer's disease; amyloid beta; choroid plexus
Affiliations: Laboratory of Neuroendocrinology, Cajal Institute, CSIC, Avda. Dr. Arce 37, 28002 Madrid, Spain.

Abstract:  The possibility that perturbed insulin/insulin-like growth factor I (IGF-I) signalling is involved in development of late-onset forms of Alzheimer's disease (AD) is gaining increasing attention. We recently reported that circulating IGF-I participates in brain amyloid beta (Abeta) clearance by modulating choroid plexus function. We now present evidence that blockade of the IGF-I receptor in the choroid plexus originates changes in brain that are reminiscent of those found in AD. In rodents, IGF-I receptor impairment led to brain amyloidosis, cognitive disturbance, and hyperphosphorylated tau deposits together with other changes found in Alzheimer's disease such as gliosis and synaptic protein loss. While these disturbances were mostly corrected by restoring receptor function, blockade of the IGF-I receptor exacerbated AD-like pathology in old mutant mice already affected of brain amyloidosis and cognitive derangement. These findings may provide new cues into the causes of late-onset Alzheimer's disease in humans giving credence to the notion that an abnormal age-associated decline in IGF-I input to the choroid plexus may contribute to development of AD in genetically prone subjects. 

Retracted: No

PubPeer comments:
 https: cosmocoffee.info viewtopic.php?f=2 t=3318 p=9070 sid=b54746c8486443e45cf0018447acf98c#p9070 ,
Coxiella burnetii DNA, but not viable bacteria, in dairy products in France
Authors: Didier Raoult
Carole Eldin
Aurélie Renvoisé
Emmanouil Angelakis
Journal: American Journal of Tropical Medicine and Hygiene (2013)
Discipline: CLINICAL MEDICINE
Keywords: Coxiella burnetii; Q fever transmission; dairy products; pasteurized; unpasteurized
Affiliations: Faculté de Médecine, Université de la Méditerranée, Marseille, France. 

Abstract:  Transmission by the oral route of Coxiella burnetii is controversial. Our objective was to evaluate dairy products in the transmission of Q fever. Pasteurized, unpasteurized, and thermized dairy products were tested for C. burnetii by using a quantitative polymerase chain reaction specific for IS1111 and IS30A spacers, culturing in human embryonic lung fibroblasts cells, and inoculation into BALB/c mice. We tested 201 products and C. burnetii was identified in 64%. Cow milk origin products were more frequently positive than goat or ewe products (P = 0.006 and P = 0.0001, respectively), and industrial food was more frequently positive than artisanal food (P &lt; 0.0001). Food made from unpasteurized milk contained higher bacteria concentrations than food made from pasteurized milk (P = 0.02). All cultures were negative and mice did not show signs of illness. Farm animals are highly infected in France but consumption of cheese and yogurt does not seem to pose a public health risk for transmission of Q fever. 

Retracted: No

PubPeer comments:
 Figure 1 in that paper ( Comparison between cycle threshold (Ct) values and log10 values of the number (nb) of copies mL of the Coxiella burnetii IS1111 spacer region, France ), published on February 4, 2013: ![file] appears identical to Figure 2 in https: doi.org 10.1371 journal.pntd.0001540 published on March 6, 2012: ![file] ,
Long noncoding RNA PVT1 promotes laryngeal squamous cell carcinoma development by acting as a molecular sponge to regulate miR‐519d‐3p
Authors: Kang Zhao
Lei Liu
Xiling Zheng
Min Xu
Tao Liu
Changming Zhou
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: laryngeal squamous cell carcinoma; long noncoding RNA PVT1; miR-519d-3p.
Affiliations: Department of Otorhinolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China., Department of Otorhinolaryngology Head and Neck Surgery, Xi'an Jiaotong University, Xi'an, Shaanxi, China., Department of General Surgery, Yan'an University Affiliated Hospital, Yan'an, Shaanxi, China.

Abstract:  Objective: This study was designed to investigate the effects and mechanism of long noncoding RNA (lncRNA) PVT1 on cell migration, proliferation, and apoptosis of laryngeal squamous cell carcinoma (LSCC). Methods: We screened lncRNAs expression profiles in four pair LSCC and matched noncancerous tissues by microarray assay. The messenger RNA levels of PVT1 in tissues and cells were evaluated by quantitative real-time polymerase chain reaction analysis. StarBase website was used to predict the target miRNAs for PVT1. And the interaction between PVT1 and target miRNA-519d-3p in LSCC cells was analyzed using dual-luciferase reporter assay. MTT assay was used to investigate the cell viability. Cell counting assay was used to explore the cell proliferation. Annexin-V propidium iodide flow cytometry was used to examine the cell apoptosis, and transwell assay was used to investigate the effects of lncRNA PVT1 on cell migration. Results: PVT1 was significantly overexpressed in human LSCC tissues and several LSCC cell lines. Upregulation of lncRNA PVT1 markedly facilitated proliferation suppressed apoptosis and promoted cell migration in LSCC cells. We further demonstrated that silencing PVT1 strikingly suppressed proliferation, promoted apoptosis, and reduced migration in LSCC cells. Further bioinformatic analysis and dual-luciferase reporter assay revealed that PVT1 could function as an oncogenic transcript partly through sponging miR-519d-3p. Besides, mechanistic investigations indicated that PVT1 could promote cell and migration through interacting with miR-519d-3p. Conclusion: LncRNA PVT1 is consistently overexpressed in human LSCC, and overexpression of lncRNA PVT1 contributes to the proliferation and migration of LSCC through inhibiting miR-519d-3p expression. 

Retracted: No

PubPeer comments:
 Figure 3 appears to have an image duplication ![file] ,
miR-221 promotes tumorigenesis in human triple negative breast cancer cells
Authors: Sangita M Baxi
Pramod P Mehta
Rounak Nassirpour
Min-Jean Yin
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Triple-negative breast cancers; apoptosis resistance; cellular proliferation; migration; invasion
Affiliations: Oncology Research, Pfizer Worldwide Research and Development, San Diego, California, United States of America.

Abstract:  Patients with triple-negative breast cancers (TNBCs) typically have a poor prognosis. TNBCs are characterized by their resistance to apoptosis, aggressive cellular proliferation, migration and invasion, and currently lack molecular markers and effective targeted therapy. Recently, miR-221/miR-222 have been shown to regulate ERα expression and ERα-mediated signaling in luminal breast cancer cells, and also to promote EMT in TNBCs. In this study, we characterized the role of miR-221 in a panel of TNBCs as compared to other breast cancer types. miR-221 knockdown not only blocked cell cycle progression, induced cell apoptosis, and inhibited cell proliferation in-vitro but it also inhibited in-vivo tumor growth by targeting p27(kip1). Furthermore, miR-221 knockdown inhibited cell migration and invasion by altering E-cadherin expression, and its regulatory transcription factors Snail and Slug in human TNBC cell lines. Therefore, miR-221 functions as an oncogene and is essential in regulating tumorigenesis in TNBCs both in vitro as well as in vivo. 

Retracted: Yes

PubPeer comments:
null, 
null, 
 April 2017 retraction:  The authors Min-Jean Yin and Rounak Nassirpour and a Pfizer representative contacted the editorial office to raise that there are image duplications in Figure 4B of this article. Pfizer has undertaken a review and deemed that important conclusions in the manuscript cannot be verified, as original images cannot be located. In light of the concerns identified, the authors and the PLOS ONE Editors retract this article. We did not receive any response or comment from Pramod Mehta. https: journals.plos.org plosone article?id=10.1371 journal.pone.0175869 Further news coverage: * 5 retractions and a sack for Pfizer lead cancer researcher Min-Jean Yin - Leonid Schneider - https: forbetterscience.com 2016 10 11 5-retractions-and-a-sack-for-pfizer-lead-cancer-researcher-min-jean-yin * Pfizer fires employee, requests five retractions - Retraction Watch - http: retractionwatch.com 2016 10 11 pfizer-fires-employee-requests-five-retractions * Pfizer Fires For Fakery - Derek Lowe - Science - https: blogs.sciencemag.org pipeline archives 2016 10 12 pfizer-fires-for-fakery * Former Pfizer Cancer Scientist Gets All 5 Papers Retracted - BioSpace - https: www.biospace.com article former-pfizer-cancer-scientist-gets-all-5-papers-retracted- ,
Histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates Toll-like receptor 4 signaling in lipopolysaccharide-stimulated mouse macrophages
Authors: William M Smith
Marc A deMoya
Yongqing Li
George C Velmahos
Wei Chong
Hasan B Alam
Eugene Y Fukudome
Baoling Liu
Zhengcai Liu
Ting Zhao
Journal: Journal of Surgical Research (2012)
Discipline: CLINICAL MEDICINE
Keywords: SAHA; LPS; Toll-like receptor 4 signaling; HSP90; acetylation
Affiliations: Department of Surgery, Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.

Abstract:  Objective: We have previously demonstrated that pretreatment and posttreatment of animals with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, can improve survival in a mouse model of lipopolysaccharide (LPS)-induced severe shock. This study was designed to assess whether SAHA affects LPS/Toll-like receptor 4 signaling through acetylation of heat shock protein 90 (HSP90) and degradation of its client protein interleukin-1 receptor-associated kinase 1 (IRAK1). Methods: RAW264.7 cells were exposed to LPS (1 μg/mL) for 2 h, followed by treatment with SAHA (10 μM) or geldanamycin (3 μM), an inhibitor of HSP90. Sham (no SAHA, no LPS) macrophages served as a control. The cells were harvested at different time points, and time zero served as the reference point. Results: LPS dramatically increased protein expression of myeloid differentiation factor 88 and IRAK1, and stimulated nuclear translocation of nuclear factor κB, leading to an increases of gene expression and protein production of tumor necrosis factor α and interleukin-6. Treatment with SAHA significantly attenuated these LPS-stimulated alterations. LPS or SAHA did not change the levels of HSP90 protein, but immunoprecipitation studies demonstrated that SAHA treatment enhanced acetylation of HSP90, and increased the dissociation of IRAK1, compared to the LPS control. Conclusions: SAHA suppresses LPS/Toll-like receptor 4 signaling in LPS-stimulated macrophages through multiple potential mechanisms. It inhibits the function of HSP90 through hyperacetylation of the chaperone protein, which results in dissociation and degradation of the client protein IRAK1 and, at least in part, leads to a decrease in nuclear translocation of nuclear factor κB and attenuation of key proinflammatory cytokine expression. 

Retracted: No

PubPeer comments:
 ![file] Suspected image duplication of Chong et al. (2012) Figure 5 from previously published article Y. Li et al. Surgery (2010) 148(2), 246-254 (Figure 3). The 2010 article contains a 4, 6, 18 hr timepoint for cytokine secretions. The 2012 article contains a suspected duplication of 6 hr and 18 hr timepoints for both TNFa and IL-6. ![file] ,
A targeted DNA-PKcs-null mutation reveals DNA-PK-independent functions for KU in V(D)J recombination
Authors: D T Weaver
C Zhu
Y Gao
F W Alt
L Davidson
J Chaudhuri
Journal: Immunity (1998)
Discipline: IMMUNOLOGY
Keywords: DNA-dependent protein kinase; Ku70; Ku80; DNA-PKcs; ionizing radiation sensitivity
Affiliations: Howard Hughes Medical Institute, The Children's Hospital, The Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract:  The DNA-dependent protein kinase (DNA-PK) consists of Ku70, Ku80, and a large catalytic subunit, DNA-PKcs. Targeted inactivation of the Ku70 or Ku80 genes results in elevated ionizing radiation (IR) sensitivity and inability to perform both V(D)J coding-end and signal (RS)-end joining in cells, with severe growth retardation plus immunodeficiency in mice. In contrast, we now demonstrate that DNA-PKcs-null mice generated by gene-targeted mutation, while also severely immunodeficient, exhibit no growth retardation. Furthermore, DNA-PKcs-null cells are blocked for V(D)J coding-end joining, but retain normal RS-end joining. Finally, while DNA-PK-null fibroblasts exhibited increased IR sensitivity, DNA-PKcs-deficient ES cells did not. We conclude that Ku70 and Ku80 may have functions in V(D)J recombination and DNA repair that are independent of DNA-PKcs. 

Retracted: No

PubPeer comments:
null, 
 #1 Figure 1B. Much more similar than you would expect. The genotypes are different. https: imgur.com VZbmrcd ,
Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals
Authors: Kiichi Watanabe
Masako Kawada
Michiru Matsumura
Keiko Muguruma
Yoshiki Sasai
Ayaka Nishiyama
Mami Matsuo-Takasaki
Takafumi Wataya
Shigenobu Yonemura
Mototsugu Eiraku
Journal: Cell stem cell (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ESC; cortical tissues; apico-basally polarized; SFEBq culture; cortical neurons
Affiliations: Organogenesis and Neurogenesis Group, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.

Abstract:  Here, we demonstrate self-organized formation of apico-basally polarized cortical tissues from ESCs using an efficient three-dimensional aggregation culture (SFEBq culture). The generated cortical neurons are functional, transplantable, and capable of forming proper long-range connections in vivo and in vitro. The regional identity of the generated pallial tissues can be selectively controlled (into olfactory bulb, rostral and caudal cortices, hem, and choroid plexus) by secreted patterning factors such as Fgf, Wnt, and BMP. In addition, the in vivo-mimicking birth order of distinct cortical neurons permits the selective generation of particular layer-specific neurons by timed induction of cell-cycle exit. Importantly, cortical tissues generated from mouse and human ESCs form a self-organized structure that includes four distinct zones (ventricular, early and late cortical-plate, and Cajal-Retzius cell zones) along the apico-basal direction. Thus, spatial and temporal aspects of early corticogenesis are recapitulated and can be manipulated in this ESC culture. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Figure S7. * Blue boxes: Panel G (hS day 59) and Panel H (hES day 59) appear to look the same, except that the green and red channels are flipped. Could the authors please check? ![file] ,
MiR-223 regulates human embryonic stem cell differentiation by targeting the IGF-1R/Akt signaling pathway
Authors: Li Zhang
Fang-Fang Huang
Hui Zeng
Yan-Hui Yu
Fang-Ping Chen
Zheng Zhang
De-Sheng Liang
Deng-Shu Wu
Jian Zhang
Xiao-Ping Chen
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: hESCs; microRNAs; FGF; IGF-1R; gene expression
Affiliations: Department of Hematology, Xiang-Ya Hospital, Central South University, Changsha, Hunan, China.

Abstract:  Currently, there are difficulties associated with the culturing of pluripotent human embryonic stem cells (hESCs), and knowledge regarding their regulatory mechanisms is limited. MicroRNAs (miRNAs) regulate gene expression and have critical functions in stem cell self-renewal and differentiation. Moreover, fibroblast growth factor (FGF) and the insulin-like growth factor receptor (IGF-1R) are key activators of signaling in hESCs. Based on the identification of complementary binding sites in miR-223 and IGF-1R mRNA, it is proposed that miR-223 acts as a local regulator of IGF-1R. Therefore, levels of miR-223 were detected in differentiated versus undifferentiated hESCs. In addition, proliferation, apoptosis, and differentiation were assayed in these two hESC populations and were compared in the presence of exogenous miR-223 and miR-223 inhibitor. Inhibition of miR-223 was found to maintain the undifferentiated state of hESCs, while addition of miR-223 induced differentiation. Furthermore, these effects were found to be likely dependent on IGF-1R/Akt signaling. 

Retracted: No

PubPeer comments:
 Figure 2. * Red and blue arrows: the middle GAPDH panels in both Figure 2D and 2E appear to overlap with the left and right panels. ![file] ,
In vitro Anticancer Effects of JI017 on Two Prostate Cancer Cell Lines Involve Endoplasmic Reticulum Stress Mediated by Elevated Levels of Reactive Oxygen Species
Authors: Seong-Gyu Ko
Deok Hyun Jung
Se Hyang Hong
Hyo In Kim
Joon-Sang Park
Yong Cheol Shin
Jin Mo Ku
Min Jeong Kim
Yun Young Kwon
Journal: Frontiers in Pharmacology (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: CHOP; JI017; ROS; cancer; er stress
Affiliations: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea., Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, South Korea., Department of Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, Seoul, South Korea.

Abstract:  Prostate cancer is the second most commonly diagnosed cancer, and prostate cancer is the second most common cause of cancer death in United States men after lung cancer. Many therapies are used to treat prostate cancer, and chemotherapy is one of the most relevant treatments. However, chemotherapy has many side effects, and repeated administration of chemotherapeutic agents leads to acquired resistance. Thus, new drugs with few side effects are needed. We investigated the molecular mechanism of action of JI017 in human prostate cancer cells. We identified an endoplasmic reticulum (ER) stress pathway that depended on the reactive oxygen species (ROS) pathway and played a crucial role in JI017-induced apoptosis. We measured cell viability by the MTS assay to determine the effect of JI017. Analysis of apoptosis, mitochondrial dysfunction, and cell cycle features was performed by flow cytometry. We used western blot and RT-PCR to measure the levels of the proteins of the unfolded protein response (UPR) pathway and apoptosis markers. Immunoprecipitation assay and transfection were used to determine the expression levels of proteins interacting with the pathways influenced by JI017 in prostate cancer cells. The anticancer effects induced by JI017 were evaluated. JI017 induced cell death that regulated apoptotic molecules and caused cell cycle arrest that inhibited the proliferation of cancer cells. Moreover, JI017 generated ROS. Accumulation of ROS caused ER stress through the PERK-eIF2α-CHOP and IRE1α-CHOP pathways. Furthermore, persistent activation of the UPR pathway induced by JI017 treatment triggered mitochondrial dysfunction, including dissipation of mitochondrial membrane potential, which activated intrinsic apoptotic pathway in human prostate cancer cells. The data indicated that N-acetyl-L-cysteine diminished apoptosis. We demonstrated that JI017 induced ER stress and cell death. Anticancer properties of JI017 in prostate cancer cells and in a human prostate cancer model involved ROS-mediated ER stress. Thus, JI017 treatment provides a new strategy for chemotherapy of prostate cancer. 

Retracted: No

PubPeer comments:
 Bands indicated by boxes are more similar than one would expect. I also find unusual similarities in bands of NF-kB gel. Clearly, the best way to dispel these doubts is to post the full blots. ![file] ,
Effects of urate-lowering agents on arrhythmia vulnerability in post-infarcted rat hearts
Authors: Shinn-Zong Lin
Tsung-Ming Lee
Nen-Chung Chang
Journal: Journal of Pharmacological Sciences (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Antioxidants; Arrhythmia; Cardiac remodeling; Heart failure.

Abstract:  Hyperuricemia has been shown to be associated with ventricular arrhythmias. However, the mechanisms remained unknown. We assessed whether different urate-lowering agents can attenuate arrhythmias through lowering urate itself or inhibiting xanthenes oxidize (XO) activity in infarcted rats. Male Wistar rats after ligating coronary artery were randomized to either allopurinol, or febuxostat, chemically unrelated inhibitors of XO, benzbromarone or vehicle for 4 weeks. Post-infarction was associated with increased oxidant stress, as measured by myocardial superoxide, isoprostane, XO activity and dihydroethidine fluorescence staining. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle-treated infarcted rats compared with sham-operated rats. Sympathetic hyperinnervation was blunted after administering both XO inhibitors, assessed by immunofluorescent analysis, Western blotting and real-time quantitative RT-PCR. Besides, the XO inhibitors-attenuated nerve growth factor levels were reversed in the presence of peroxynitrite generator. Arrhythmic scores in the XO inhibitors-treated infarcted rats were significantly lower than that in vehicle. For similar levels of urate lowering, the uricosuric agent benzbromarone had no beneficial effects on oxidative stress, sympathetic hyperinnervation or arrhythmia vulnerability. Chronic use of XO inhibitors, but not uricosuric agent, down-regulated sympathetic innervation probably through a superoxide-dependent pathway and plays a role in the beneficial effect on arrhythmogenic response. 

Retracted: No

PubPeer comments:
 Figure 3D and 3E appear to overlap but represent different treatments. Approximate area of overlap shown below with green boxes on original and the second image with enhanced brightness. *** Original ![file] *** Enhance brightness ![file] ,
TGF  Signaling in the Pancreatic Tumor Microenvironment Promotes Fibrosis and Immune Evasion to Facilitate Tumorigenesis
Authors: Deyu Fang
Naomi Akagi
Rosa Hwang
David J Bentrem
Paul J Grippo
Brian DeCant
David W Dawson
Andrew M Diaz
Hidayatullah G Munshi
Barbara Jung
Daniel R Principe
Emman Mascariñas
Elizabeth A Wayne
Boris Pasche
Journal: Cancer Research (2016)
Discipline: CLINICAL MEDICINE
Keywords: TGFβ; pancreatic carcinogenesis; tumor progression; mouse models; TGFBR deficiency

Abstract:  In early pancreatic carcinogenesis, TGFβ acts as a tumor suppressor due to its growth-inhibitory effects in epithelial cells. However, in advanced disease, TGFβ appears to promote tumor progression. Therefore, to better understand the contributions of TGFβ signaling to pancreatic carcinogenesis, we generated mouse models of pancreatic cancer with either epithelial or systemic TGFBR deficiency. We found that epithelial suppression of TGFβ signals facilitated pancreatic tumorigenesis, whereas global loss of TGFβ signaling protected against tumor development via inhibition of tumor-associated fibrosis, stromal TGFβ1 production, and the resultant restoration of antitumor immune function. Similarly, TGFBR-deficient T cells resisted TGFβ-induced inactivation ex vivo, and adoptive transfer of TGFBR-deficient CD8(+) T cells led to enhanced infiltration and granzyme B-mediated destruction of developing tumors. These findings paralleled our observations in human patients, where TGFβ expression correlated with increased fibrosis and associated negatively with expression of granzyme B. Collectively, our findings suggest that, despite opposing the proliferation of some epithelial cells, TGFβ may promote pancreatic cancer development by affecting stromal and hematopoietic cell function. Therefore, the use of TGFBR inhibition to target components of the tumor microenvironment warrants consideration as a potential therapy for pancreatic cancer, particularly in patients who have already lost tumor-suppressive TGFβ signals in the epithelium. Cancer Res; 76(9); 2525-39. ©2016 AACR. 

Retracted: No

PubPeer comments:
 ![file] , 
 #1 RE: * Different images in 400X magnification * -- What on earth is your point? Did you expect the two boxed images to be the same?? Are you concerned that the 400x images are not portions of the 100x images above?? If the latter, why is this a problem?? Before posting, try doing a bit more thinking and provide some explanation of your reasoning. ,
Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation
Authors: Xi He
Raymond Habas
Igor B Dawid
Journal: Genes & Development (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Wnt/Frizzled signaling; cell polarity; cell movements; vertebrate gastrulation; Rho

Abstract:  Wnt/Frizzled (Fz) signaling controls cell polarity/movements during vertebrate gastrulation via incompletely defined mechanisms. We demonstrated previously that Wnt/Fz activation of Rho, a GTPase and regulator of cytoskeletal architecture, is essential for vertebrate gastrulation. Here we report that in mammalian cells and Xenopus embryos, Wnt/Fz signaling coactivates Rho and Rac, another GTPase and distinct regulator of cytoskeletal architecture. Wnt/Fz activation of Rac is independent of Rho and mediates Wnt/Fz activation of Jun N-terminal kinase (JNK). Dishevelled (Dvl), a cytoplasmic protein downstream of Fz, forms a Wnt-induced complex with Rac independent of the Wnt-induced Dvl-Rho complex. Depletion or inhibition of Rac function perturbs Xenopus gastrulation without affecting Wnt/Fz activation of the Rho or beta-catenin pathway. We propose that parallel activation of Rac and Rho pathways by Wnt/Fz signaling is required for cell polarity and movements during vertebrate gastrulation. 

Retracted: No

PubPeer comments:
 Figure 6B u2013 more similar than expected. Could authors check it please? ![file] Figure 3D u2013 Possible differential splicing ![file] ,
MiR-101 inhibits the proliferation and metastasis of lung cancer by targeting zinc finger E-box binding homeobox 1
Authors: Wenjuan Chen
Yangrong Song
Le Han
Zheng Zhao
Yanmin Xia
Tao Jiang
Hao Cheng
Journal: American journal of translational research (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: MicroRNA-101; lung cancer; metastasis; proliferation; zinc finger E-box binding homeobox 1.
Affiliations: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University Xi'an 710038, Shaanxi, China., Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province Xi'an 710038, Shaanxi, China.

Abstract:  MicroRNAs (miRNAs) are involved in the development and progression of lung cancer. MicroRNA-101 (miR-101) displays crucial properties in non-small cell lung cancer (NSCLC) by negatively regulating cell proliferation and invasion, but the underlying molecular mechanisms remain largely unknown. In this study, we found that miR-101 was underexpressed while zinc finger E-box binding homeobox 1 (ZEB1) was highly upregulated in NSCLC tissues and cells. The downregulation of miR-101 was positively associated with lymph node metastasis and poor prognosis of NSCLC patients. Dual-luciferase reporter assay showed that miR-101 directly targeted ZEB1 in NSCLC cells. Enforced expression of miR-101 significantly inhibited NSCLC cell proliferation, apoptosis resistance, migration, and invasion in vitro, which were attenuated by ZEB1 overexpression and phenocopied by ZEB1 knockdown, respectively. Consistently, miR-101 retarded NSCLC growth and metastasis in vivo. The findings indicated that miR-101 suppressed NSCLC growth and metastasis by targeting ZEB1, thereby providing new evidence of miR-101 as a potential therapeutic target for NSCLC patients. 

Retracted: No

PubPeer comments:
 *[left]* Fig 1H.  Correlation of the ZEB1 level and miR-101 expression in NSCLC cells. *[right]* Fig 1E from [Wu et al (2016)] .  Spearmanu2019s correlation analysis between miR-101 and ZEB1 in OSCC specimens analyzed by qPCR assay . ![file] Surprisingly many data points in common. , 
 *[left]* Fig 1B.  Kaplan-Meier survival curves showed lower five-year overall survival rate of NSCLC patients with low miR-101 levels (n = 73) compared with individuals with high miR-101 expression (n = 87). *[right]* Fig 1B from [Wu et al (2016)] .  Kaplan-Meier survival curves of 40 patients with OSCCs divided by miR-101 expression. Log-rank test was used for survival analysis . Unexpectedly similar. ![file] ,
Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress
Authors: Ck Prashant
Saba Naqvi
Farhan Jalees Ahmed
Mohammad Samim
An Maitra
Amit K Dinda
Mz Abdin
Journal: International Journal of Nanomedicine (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: J774 cell line; MTT assay; cytotoxicity; superparamagnetic iron oxide nanoparticles.
Affiliations: Faculty of Engineering and Interdisciplinary Sciences, Jamia Hamdard, Hamdard University, New Delhi, India.

Abstract:  Iron oxide nanoparticles with unique magnetic properties have a high potential for use in several biomedical, bioengineering and in vivo applications, including tissue repair, magnetic resonance imaging, immunoassay, drug delivery, detoxification of biologic fluids, cell sorting, and hyperthermia. Although various surface modifications are being done for making these nonbiodegradable nanoparticles more biocompatible, their toxic potential is still a major concern. The current in vitro study of the interaction of superparamagnetic iron oxide nanoparticles of mean diameter 30 nm coated with Tween 80 and murine macrophage (J774) cells was undertaken to evaluate the dose- and time-dependent toxic potential, as well as investigate the role of oxidative stress in the toxicity. A 15-30 nm size range of spherical nanoparticles were characterized by transmission electron microscopy and zeta sizer. MTT assay showed &gt;95% viability of cells in lower concentrations (25-200 μg/mL) and up to three hours of exposure, whereas at higher concentrations (300-500 μg/mL) and prolonged (six hours) exposure viability reduced to 55%-65%. Necrosis-apoptosis assay by propidium iodide and Hoechst-33342 staining revealed loss of the majority of the cells by apoptosis. H₂DCFDDA assay to quantify generation of intracellular reactive oxygen species (ROS) indicated that exposure to a higher concentration of nanoparticles resulted in enhanced ROS generation, leading to cell injury and death. The cell membrane injury induced by nanoparticles studied using the lactate dehydrogenase assay, showed both concentration- and time-dependent damage. Thus, this study concluded that use of a low optimum concentration of superparamagnetic iron oxide nanoparticles is important for avoidance of oxidative stress-induced cell injury and death. 

Retracted: Yes

PubPeer comments:
 The authors may wish to examine Figure 6. It appears that the insets for Figure 6b and 6c are the same. *** ![file] ,
Reversal of prolonged obesity-associated cerebrovascular dysfunction by inhibiting microglial Tak1
Authors: Guo Zhang
Juxue Li
Tingting Zhang
Xueer Cheng
Faming Zhao
Zhuo Chen
Junxia Qi
Susu Pan
Lei Zhang
Qing Shen
Shanshan Zhang
Dongsheng Cai
Journal: Nature Neuroscience (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: obesity; cerebrovascular dysfunction; microglial Tak1; brainstem; basilar artery abnormalities
Affiliations: Key Laboratory of Environmental Health, Ministry of Education, Department of Toxicology, School of Public Health, Tongji Medical College, Wuhan, China., Institute for Brain Research, Wuhan, China., Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China., State Key Laboratory of Reproductive Medicine, Nanjing, China., Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China., Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA. ., Key Laboratory of Environmental Health, Ministry of Education, Department of Toxicology, School of Public Health, Tongji Medical College, Wuhan, China. ., Institute for Brain Research, Wuhan, China. ., Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China. .

Abstract:  Prolonged obesity is associated with cerebrovascular dysfunction; however, the underlying mechanisms remain largely unclear. In the present study, using a prolonged obesity mouse model that suffers from basilar artery (BA) abnormalities, we find that microglial transforming growth factor β-activated kinase 1 (Tak1) is over-activated in the brainstem. Both pharmacological inhibition primarily in the brainstem and genetic microglia-selective deletion of Tak1 ameliorated BA vascular dysfunction. Conversely, microglia-specific activation of Tak1 in the brainstem was sufficient to cause an impairment in BA function in chow-fed mice. Mechanistically, Tak1 activation leads to increased interleukin-18 (IL-18) production, whereas blockade of IL-18 receptor in the brain helped protect against cerebrovascular dysfunction despite prolonged obesity. Microglia-selective deletion of Tak1 also protects against ischemic stroke in prolonged obesity. Taken together, these findings provide evidence that microglial Tak1 in the brain, and particularly the brainstem, contributes to the pathogenesis of obesity-associated cerebrovascular dysfunction. 

Retracted: No

PubPeer comments:
 Great paper and well done! The only thing I m confused about is how the lentiviral vector was validated to be expressed in microglia. Looking at the histology (EGFP expression with the lentivirus), it looks like to me that these cells might be astrocytes, not microglia (Ext data fig 6b). ![file] Also, from the flow cytometry plots, it seems like only ~2% of microglia express EGFP in the brain region of interest, which wouldn t match up with the histology showing lots of cells expressing EGFP. ![file] ,
Cognitive neuroscience. Unlearning implicit social biases during sleep
Authors: Iliana M Vargas
Jessica D Creery
Galen V Bodenhausen
Ken A Paller
James W Antony
Xiaoqing Hu
Journal: Science (2015)
Discipline: Multidisciplinary
Keywords: egalitarianism; tolerance; social biases; unconscious; training
Affiliations: Department of Psychology, Northwestern University, Evanston, IL 60208, USA. Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA., Department of Psychology, Northwestern University, Evanston, IL 60208, USA. Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA., Department of Psychology, Northwestern University, Evanston, IL 60208, USA., Department of Psychology, Northwestern University, Evanston, IL 60208, USA. .

Abstract:  Although people may endorse egalitarianism and tolerance, social biases can remain operative and drive harmful actions in an unconscious manner. Here, we investigated training to reduce implicit racial and gender bias. Forty participants processed counterstereotype information paired with one sound for each type of bias. Biases were reduced immediately after training. During subsequent slow-wave sleep, one sound was unobtrusively presented to each participant, repeatedly, to reactivate one type of training. Corresponding bias reductions were fortified in comparison with the social bias not externally reactivated during sleep. This advantage remained 1 week later, the magnitude of which was associated with time in slow-wave and rapid-eye-movement sleep after training. We conclude that memory reactivation during sleep enhances counterstereotype training and that maintaining a bias reduction is sleep-dependent. 

Retracted: No

PubPeer comments:
null, 
 At the start of this year, an independent group were unable to replicate the findings of this study: https: journals.plos.org plosone article?id=10.1371 journal.pone.0211416 From the abstract:  Contrary to the results reported by Hu et al., we found no effect of cueing on implicit bias, either immediately following the nap or one week later. In fact, bias was non-significantly greater for cued than for uncued stimuli. Our failure to detect an effect of cueing on implicit bias could indicate either that the original report was a false positive, or that the current study is a false negative. However, several factors argue against Type II error in the current study. Critically, this replication was powered at 0.9 for detecting the originally reported cueing effect. Additionally, the 95% confidence interval for the cueing effect in the present study did not overlap with that of the originally reported effect; therefore, our observations are not easily explained as a noisy estimate of the same underlying effect. Ultimately, the outcome of this replication study reduces our confidence that cueing during sleep can reduce implicit bias. ,
High expression of kinesin light chain-2, a novel target of miR-125b, is associated with poor clinical outcome of elderly non-small-cell lung cancer patients
Authors: M Wang
X Zhu
D Li
L Chen
Z Sha
N Li
Journal: British Journal of Cancer (2015)
Discipline: CLINICAL MEDICINE
Keywords: MiR-125b; Kinesin-1 light chain-2; NSCLC; cell migration; target genes
Affiliations: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Republic of China.

Abstract:  Background: MiR-125b has critical role in non-small-cell lung cancer (NSCLC) cell migration, and its target genes have not been elucidated. Kinesin-1 light chain (KLC)-2 was predicted as one of miR-125b's targets by bioinformatics analysis. This study is to identify the function of KLC2 and its interaction with miR-125b in NSCLC. Methods: Kinesin-1 light chain-2 protein expression and its clinical relevance were analysed in 140 matched NSCLC and adjacent non-neoplastic lung tissues. Both KLC2 gain- and loss-of-function analyses were performed in NSCLC cell lines by transient transfection. The direct interaction between KLC2 and miR-125b was confirmed by a luciferase reporter assay and a transient co-transfection assay as well as an analysis of eight matched clinical samples. Results: KLC2 protein was upregulated in NSCLC cell lines and tissues, and was an independent predictor of poor prognosis for elderly NSCLC patients. Kinesin-1 light chain-2 remarkably enhanced the invasive and migratory ability of NSCLC cells. MiR-125b inhibited KLC2 3'-untranslated region luciferase activity and protein expression, and inversely correlated with KLC2 expression in clinical samples. Kinesin-1 light chain-2 almost completely reversed miR-125b-induced inhibition on migration and invasion. Conclusions: Kinesin-1 light chain-2 protein overexpression predicts poor survival in elderly NSCLC patients. Kinesin-1 light chain-2 acts as a proto-oncogene and a functional target of miR-125b in NSCLC cells. 

Retracted: No

PubPeer comments:
 Images in Figure 4C appear to overlap. *** ![file] , 
 Similar issue in Figure 2C. These types of errors are sometimes seen in papermill papers. *** ![file] ,
A scaling normalization method for differential expression analysis of RNA-seq data
Authors: Mark D Robinson
Alicia Oshlack
Journal: Genome biology (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RNA-seq; transcriptome surveys; normalization; differential expression; steady state RNA
Affiliations: Bioinformatics Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Australia. 

Abstract:  The fine detail provided by sequencing-based transcriptome surveys suggests that RNA-seq is likely to become the platform of choice for interrogating steady state RNA. In order to discover biologically important changes in expression, we show that normalization continues to be an essential step in the analysis. We outline a simple and effective method for performing normalization and show dramatically improved results for inferring differential expression in simulated and publicly available data sets. 

Retracted: No

PubPeer comments:
null, 
 #1 #1 It s very difficult, if not impossible, to run a completely straight blot with this many samples. Most blot apparatuses top out at 15 samples, so if you ve got 12 + a ladder, you re bound to have samples at the end that are at different angles. All you are seeing is the samples on end of the gel curling a bit as they don t run perfectly straight due to the position of the electrodes. You can see quite clearly in multiple proteins that the width of bands for the same protein can be somewhat variable, which is not at all novel or reason for concern. The image has not been manipulated - how could the authors have affected the width of the bands? This is a practical outcome of the SDS-PAGE and nothing more. ,
Proteomic characterization of the outer membrane vesicle of Pseudomonas putida KT2440
Authors: Gun-Hwa Kim
Yeol Gyun Lee
Sang-Yeop Lee
Kyeong Ryang Park
Edmond Changkyun Park
Sung Ho Yun
Yeonhee Hong
Seung Il Kim
Chi-Won Choi
Sang-Hyun Kim
Journal: Journal of Proteome Research (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Pseudomonas putida KT2440; mass spectrometry; outer membrane vesicle.
Affiliations: Division of Life Science, Korea Basic Science Institute , Daejeon 305-806, Republic of Korea., Division
of Life Science, Korea Basic Science Institute, Daejeon 305-806, Republic of Korea, Department
of Biological Science and Biotechnology, Hannam University, Daejeon 306-791, Republic of Korea, Viral
infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea

Abstract:  Outer membrane vesicles (OMVs) are produced by various pathogenic Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. In this study, we isolated OMVs from a representative soil bacterium, Pseudomonas putida KT2440, which has a biodegradative activity toward various aromatic compounds. Proteomic analysis identified the outer membrane proteins (OMPs) OprC, OprD, OprE, OprF, OprH, OprG, and OprW as major components of the OMV of P. putida KT2440. The production of OMVs was dependent on the nutrient availability in the culture media, and the up- or down-regulation of specific OMPs was observed according to the culture conditions. In particular, porins (e.g., benzoate-specific porin, BenF-like porin) and enzymes (e.g., catechol 1,2-dioxygenase, benzoate dioxygenase) for benzoate degradation were uniquely found in OMVs prepared from P. putida KT2440 that were cultured in media containing benzoate as the energy source. OMVs of P. putida KT2440 showed low pathological activity toward cultured cells that originated from human lung cells, which suggests their potential as adjuvants or OMV vaccine carriers. Our results suggest that the protein composition of the OMVs of P. putida KT2440 reflects the characteristics of the total proteome of P. putida KT2440. 

Retracted: No

PubPeer comments:
 The cytometric analysis in Migure 6C and 6D appears to include two sets of repeated graphs. Could the authors examine and comment? *** ![file] *** Closeup ![file] ,