PReD-Bench/PRed-Bench huggingface dataset:
NBK/BIK antagonizes MCL-1 and BCL-XL and activates BAK-mediated apoptosis in response to protein synthesis inhibition
Authors: Alam Nur-E-Kamal
Masayori Inouye
Takeshi Yoshida
Eileen White
Robin Mathew
Tsutomu Shimazu
Junjie Zhang
Yonglong Zhang
Kurt Degenhardt
Journal: Genes & development (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Ribonucleases; antibiotics; bacterial toxins; viruses; protein synthesis
Affiliations: Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

Abstract:  Ribonucleases, antibiotics, bacterial toxins, and viruses inhibit protein synthesis, which results in apoptosis in mammalian cells. How the BCL-2 family of proteins regulates apoptosis in response to the shutoff of protein synthesis is not known. Here we demonstrate that an Escherichia coli toxin, MazF, inhibited protein synthesis by cleavage of cellular mRNA and induced apoptosis in mammalian cells. MazF-induced apoptosis required proapoptotic BAK and its upstream regulator, the proapoptotic BH3-only protein NBK/BIK, but not BIM, PUMA, or NOXA. Interestingly, in response to MazF induction, NBK/BIK activated BAK by displacing it from anti-apoptotic proteins MCL-1 and BCL-X(L) that sequester BAK. Furthermore, NBK/BIK- or BAK-deficient cells were resistant to cell death induced by pharmacologic inhibition of translation and by virus-mediated shutoff of protein synthesis. Thus, the BH3-only protein NBK/BIK is the apical regulator of a BAK-dependent apoptotic pathway in response to shutoff of protein synthesis that functions to displace BAK from sequestration by MCL1 and BCL-X(L). Although NBK/BIK is dispensable for development, it is the BH3-only protein targeted for inactivation by viruses, suggesting that it plays a role in pathogen/toxin response through apoptosis activation. 

Retracted: No

PubPeer comments:
 Figure 7B seems to be a collage, and the loading controls do not seem to correspond to the other images.![file] ,
Ouabain induces endocytosis of plasmalemmal Na/K-ATPase in LLC-PK1 cells by a clathrin-dependent mechanism
Authors: Sankaridrug M Periyasamy
Riad Kesiry
Zijian Xie
Jiang Liu
Deepak Malhotra
Joseph I Shapiro
Journal: Kidney International (2004)
Discipline: CLINICAL MEDICINE
Keywords: ouabain; Na/K-ATPase; endocytosis; clathrin; signaling pathway
Affiliations: The Department of Medicine, Medical College of Ohio, Toledo, Ohio, USA.

Abstract:  Background: We have demonstrated that ouabain causes dose- and time-dependent decreases in (86)Rb uptake in porcine proximal tubular (LLC-PK1) cells. The present study addresses the molecular mechanisms involved in this process. Methods: Studies were performed with cultured LLC-PK1 and Src family kinase deficient (SYF) cells. Results: We found that 50 nmol/L ouabain applied to the basal, but not apical, aspect for 12 hours caused decreases in the plasmalemmal Na/K-ATPase. This loss of plasmalemmal Na/K-ATPase reverses completely within 12 to 24 hours after removal of ouabain. Ouabain also increased the Na/K-ATPase content in both early and late endosomes, activated phosphatidylinositol 3-kinase (PI(3)K), and also caused a translocation of some Na/K-ATPase to the nucleus. Immunofluorescence demonstrated that the Na/K-ATPase colocalized with clathrin both before and after exposure to ouabain, and immunoprecipitation experiments confirmed that ouabain stimulated interactions among the Na/K-ATPase, adaptor protein-2 (AP-2), and clathrin. Potassium (K) depletion, chlorpromazine, or PI(3)K inhibition all significantly attenuated this ouabain-induced endocytosis. Inhibition of the ouabain-activated signaling process through Src by 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) significantly attenuated ouabain-induced endocytosis. Moreover, experiments performed in SYF cells demonstrated that ouabain induced increases in the endocytosis of the Na/K-ATPase when Src was reconstituted (SYF+), but not in the Src-deficient (SYF-) cells. Conclusion: These data demonstrate that ouabain stimulates a clathrin-dependent endocytosis pathway that translocates the Na/K-ATPase to intracellular compartments, thus suggesting a potential role of endocytosis in ouabain-induced signal transduction as well as proximal tubule sodium handling. 

Retracted: No

PubPeer comments:
 Figure 9A * Red boxes: Two panels look similar to each other * Blue boxes: Two panels look similar to each other ![file] , 
 Corrigendum, December 2021: https: www.kidney-international.org article S0085-2538(21)00944-3 fulltext  Upon reviewing the above-stated article, the authors realized that they had inadvertently duplicated an [sic] inverted a panel. The authors have corrected the middle panel of Figure 9a, which contained incorrect blots representing the immunoprecipitation of AP-2u03b1 and then immunoblotting for u03b11 subunit and AP-2u03b1. The authors would like to apologize for any inconvenience caused. I thank the authors and journal for correcting this error. ,
Differences in digit ratios between gay men who prefer receptive versus insertive sex roles indicate a role for prenatal androgen
Authors: Cynthia L Jordan
Ashlyn Swift-Gallant
S Marc Breedlove
Christopher J Breedlove
Christina A Major
Victor Di Rita
Journal: Scientific Reports (2021)
Discipline: Multidisciplinary
Keywords: androgens; prenatal; 2D:4D; gay men; anal sex role
Affiliations: Department of Psychology, Memorial University of Newfoundland, 232 Elizabeth Ave., St. John's, NL, A1B 3X9, Canada. ., Psychology Department and Neuroscience Program, Michigan State University, 293 Farm Lane, East Lansing, MI, 48824, USA. ., Psychology Department and Neuroscience Program, Michigan State University, 293 Farm Lane, East Lansing, MI, 48824, USA., Department of Psychology, Memorial University of Newfoundland, 232 Elizabeth Ave., St. John's, NL, A1B 3X9, Canada.

Abstract:  Among non-human mammals, exposure to androgens during critical periods of development leads to gynephilia (attraction to females), whereas the absence or low levels of prenatal androgens leads to androphilia (attraction to males). However, in humans, retrospective markers of prenatal androgens have only been associated with gynephilia among women, but not with androphilia among men. Here, we asked whether an indirect indication of prenatal androgen exposure, 2D:4D, differs between subsets of gay men delineated by anal sex role (ASR). ASR was used as a proxy for subgroups because ASR groups tend to differ in other measures affected by brain sexual differentiation, such as gender conformity. First, we replicated the finding that gay men with a receptive ASR preference (bottoms) report greater gender nonconformity (GNC) compared to gay men with an insertive ASR preference (tops). We then found that Tops have a lower (male-typical) average right-hand digit ratio than Bottoms, and that among all gay men the right-hand 2D:4D correlated with GNC, indicating that a higher (female-typical) 2D:4D is associated with increased GNC. Differences were found between non-exclusive and exclusive same-sex attraction and GNC, and ASR group differences on digit ratios do not reach significance when all non-heterosexual men are included in the analyses, suggesting greater heterogeneity in the development of non-exclusive same-sex sexual orientations. Overall, results support a role for prenatal androgens, as approximated by digit ratios, in influencing the sexual orientation and GNC of a subset of gay men. 

Retracted: No

PubPeer comments:
 The handling of ethnicity in this manuscript is truly problematic. By  ranking various ethnic groups according to an arbitrary scale, the authors would statistically equate an equally mixed sample of Causasion (1) and Chinese (3) subjects as fully equivalent to a sample containing exclusively Black (2) subjects. The authors analyze their data with a  rank test and report average values and SDs in Table 1. ,
Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo
Authors: I Lambertz
M A Dyer
J-C Marine
J Vandesompele
P Mestdagh
D Nittner
G Denecker
Journal: Cell Death and Differentiation (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Dicer; haploinsufficiency; microRNA; retinoblastoma; tumor suppressor.
Affiliations: Laboratory for Molecular Cancer Biology, VIB-UGent, Ghent B9052, Belgium.

Abstract:  Human tumors are characterized by widespread reduction in microRNA (miRNA) expression, although it is unclear how such changes come about and whether they have an etiological role in the disease. Importantly, miRNA knockdown has been shown to enhance the tumorigenic potential of human lung adenocarcinoma cells. A defect in miRNA processing is one possible mechanism for global downregulation. To explore this possibility in more detail in vivo, we have manipulated Dicer1 gene dosage in a mouse model of retinoblastoma. We show that although monoallelic loss of Dicer1 does not affect normal retinal development, it dramatically accelerates tumor formation on a retinoblastoma-sensitized background. Importantly, these tumors retain one wild-type Dicer1 allele and exhibit only a partial decrease in miRNA processing. Accordingly, in silico analysis of human cancer genome data reveals frequent hemizygous, but not homozygous, deletions of DICER1. Strikingly, complete loss of Dicer1 function in mice did not accelerate retinoblastoma formation. miRNA profiling of these tumors identified members of the let-7 and miR-34 families as candidate tumor suppressors in retinoblastoma. We conclude that Dicer1 functions as a haploinsufficient tumor suppressor. This finding has implications for cancer etiology and cancer therapy. 

Retracted: No

PubPeer comments:
 Figure 2A. Much more similar than expected. ![file] ,
STK33 Promotes Growth and Progression of Pancreatic Cancer as a Critical Downstream Mediator of HIF1α
Authors: Yiqi Du
Jiawei Du
Zhiliang Jia
Ying Chen
Xiangyu Kong
Fanyang Kong
Keping Xie
Xuan Deng
Dacheng Xie
Zhaoshen Li
Lei Li
Jianwei Zhu
Journal: Cancer research (2017)
Discipline: CLINICAL MEDICINE
Keywords: STK33; pancreatic ductal adenocarcinoma; HIF1α; proliferation; metastatic progression
Affiliations: Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas., Department of Gastroenterology, Changhai Hospital, Shanghai, P.R. China., Department of Pathology, Changhai Hospital, Shanghai, P.R. China., Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, P.R. China., Department of Oncology and Tumor Institute, Shanghai East Hospital, Shanghai Tongji University, Shanghai, P.R. China., Department of Gastroenterology, Changhai Hospital, Shanghai, P.R. China.  ., Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.  .

Abstract:  The serine/threonine kinase STK33 has been implicated in cancer cell proliferation. Here, we provide evidence of a critical role for STK33 in the pathogenesis and metastatic progression of pancreatic ductal adenocarcinoma (PDAC). STK33 expression in PDAC was regulated by the hypoxia-inducible transcription factor HIF1α. In human PDAC specimens, STK33 was overexpressed and associated with poor prognosis. Enforced STK33 expression promoted PDAC proliferation, migration, invasion, and tumor growth, whereas STK33 depletion exerted opposing effects. Mechanistic investigations showed that HIF1α regulated STK33 via direct binding to a hypoxia response element in its promoter. In showing that dysregulated HIF1α/STK33 signaling promotes PDAC growth and progression, our results suggest STK33 as a candidate therapeutic target to improve PDAC treatment. Cancer Res; 77(24); 6851-62. ©2017 AACR. 

Retracted: No

PubPeer comments:
 The bands of HA in Mock and control group in Figure 5A is unbelievably  perfect . Please show the original WB data to help clarify it? ![file] , 
 Dear Cheilosia, Thank you for raising the concern about the relatively clean WB pattern of HA in the Mock and Control groups from the current experiment. The high specificity of HA Tag antibody from Thermo Fisher Scientific (catalog no. 26183) has been widely examined in many laboratories all over the world. To our knowledge, the unspecific bands could be diminished by modified WB procedures, such as prolonged blocking time and appropriate concentration of primary and secondary antibodies. Furthermore, as the HA tag was used to identify the exogenous Hif1a gene expression, any striking band weighs from 90 to 130 kDa in the Mock and Control groups was not supposed to be detected. Overall, we attached the original figure to better explain this issue. ![file] ,
Robinin modulates doxorubicin-induced cardiac apoptosis by TGF-β1 signaling pathway in Sprague Dawley rats
Authors: A Abraham
P A Janeesh
Journal: Biomedicine & Pharmacotherapy (2014)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Cardiac markers; Cardiac toxicity; Doxorubicin; Robinin.
Affiliations: Department of Biochemistry, School of Life sciences, University of Kerala, Thiruvananthapuram, Kariavattom Campus, 695 581, Kerala, India., Department of Biochemistry, School of Life sciences, University of Kerala, Thiruvananthapuram, Kariavattom Campus, 695 581, Kerala, India. Electronic address: .

Abstract:  The study focussed on the cardioprotective effect of robinin on doxorubicin-induced cardio-toxicity in Sprague Dawley rats. After the experimental period, animals were sacrificed and the various parameters such as cardiac markers, toxicity parameters, antioxidant status, ROS generation, lipid peroxidation status and inflammatory parameters were assessed. Gene expression study by RT-PCR analysis and proteins expression study by western blotting were done. Doxorubicin causes significant increase in the levels of cardiac marker enzymes, namely lactate dehydrogenase (LDH), creatine phospokinase (CPK), toxicity parameters like serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT). Antioxidant enzyme levels were decreased; lipid peroxidation products in heart tissue and inflammatory markers, namely cyclooxygenase (COX2) and lipooxygenase (LOX15) were significantly increased. Gene expression study by RT-PCR analysis of transforming growth factor-β1 (TGF-β1), Smad2, murine double minute (Mdm2), Smad3, cyclin-dependent kinase inhibitor 2A (CDKN2A), Smad4 and Smad7 were significantly altered. The western blotting study of p53, Bcl-2 and Bax also showed altered expression. The supplementation of the Robinin along with DOX caused normalised level of all the above parameters and cardio-toxicity. This study revealed the cardioprotective nature of Robinin on doxorubicin-induced cardiac toxicity by modulating TGF-β1 signaling pathway in Sprague Dawley rats. 

Retracted: No

PubPeer comments:
 The gel images were reused as inverted images in the same publication stating different experimental conditions. Could the authors clarify this? ![file] ,
The Fas/Fas ligand death receptor pathway contributes to phenylalanine-induced apoptosis in cortical neurons
Authors: Yongguo Yu
Zhongwei Lv
Yu Ding
Qihua Fu
Yongnian Shen
Da Fu
Tingting Yu
Xiaoping Zhang
Zhaohui Lu
Peirong Yang
Xiaodong Huang
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Phenylketonuria; PAH gene; apoptosis; mitochondria; Fas receptor
Affiliations: Department of Internal Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract:  Phenylketonuria (PKU), an autosomal recessive disorder of amino acid metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene, leads to childhood mental retardation by exposing neurons to cytotoxic levels of phenylalanine (Phe). A recent study showed that the mitochondria-mediated (intrinsic) apoptotic pathway is involved in Phe-induced apoptosis in cultured cortical neurons, but it is not known if the death receptor (extrinsic) apoptotic pathway and endoplasmic reticulum (ER) stress-associated apoptosis also contribute to neurodegeneration in PKU. To answer this question, we used specific inhibitors to block each apoptotic pathway in cortical neurons under neurotoxic levels of Phe. The caspase-8 inhibitor Z-IETD-FMK strongly attenuated apoptosis in Phe-treated neurons (0.9 mM, 18 h), suggesting involvement of the Fas receptor (FasR)-mediated cell death receptor pathway in Phe toxicity. In addition, Phe significantly increased cell surface Fas expression and formation of the Fas/FasL complex. Blocking Fas/FasL signaling using an anti-Fas antibody markedly inhibited apoptosis caused by Phe. In contrast, blocking the ER stress-induced cell death pathway with salubrinal had no effect on apoptosis in Phe-treated cortical neurons. These experiments demonstrate that the Fas death receptor pathway contributes to Phe-induced apoptosis and suggest that inhibition of the death receptor pathway may be a novel target for neuroprotection in PKU patients. 

Retracted: No

PubPeer comments:
 The  Caspase-8 row of Western immuno-blots in Fig. 2C and Fig. 3C originated from the same source, though with changed image contrast. ![file] Note the features in the background , 
 Thanks for raising this issue, we have contacted the journal and uploaded the raw data of all the relevant results of the article for erratum ,
Korean Red Ginseng Suppresses Metastasis of Human Hepatoma SK-Hep1 Cells by Inhibiting Matrix Metalloproteinase-2/-9 and Urokinase Plasminogen Activator
Authors: Guan-Jhong Huang
Yuan-Shiun Chang
Wei Chao
Yu-Ling Ho
Kun-Cheng Li
Journal: Evidence-based Complementary and Alternative Medicine (2012)
Discipline: CLINICAL MEDICINE
Keywords: Korean red ginseng; ginsenosides; anticancer effect; antimetastatic effect; hepatoma
Affiliations: Department of Nursing, Hungkuang University, Taichung 433, Taiwan., School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 40402, Taiwan, Chinese Crude Drug Pharmacy, China Medical University Hospital, Taichung 404, Taiwan

Abstract:  Korean red ginseng and ginsenosides have been claimed to possess wide spectrum of medicinal effects, of which anticancer effect is one. The present study was undertaken to investigate the antimetastatic effect of Korean red ginseng on human hepatoma as well as possible mechanisms. The inhibitory effect of the water extract of Korean red ginseng (WKRG) on the invasion and motility of SK-Hep1 cells was evaluated by the Boyden chamber assay in vitro. Without causing cytotoxicity, WKRG exerted a dose-dependent inhibitory effect on the invasion and motility, but not adhesion, of highly metastatic SK-Hep1 cells. Zymography analyses revealed significant downregulating effects on MMP-2, MMP-9, and uPA activities in SK-Hep1 cells. Western blot analyses also showed that WKRG treatment caused dose-dependent decreases in MMP-2 and MMP-9 protein expressions. Moreover, WKRG increased the levels of TIMP-1, TIMP-2, and PAI-1. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by WKRG, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 and uPA expressions of SK-Hep1 cells. 

Retracted: No

PubPeer comments:
 image duplications ![file] Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,
Changes in the first postoperative night bispectral index of patients after thyroidectomy with different types of primary anesthetic management: a randomized controlled trial
Authors: Feng Jin
Hong Ma
Zhi-Lin Wang
Huang-Wei Lu
Wen-Fei Tan
Journal: Journal of clinical monitoring and computing (2018)
Discipline: CLINICAL MEDICINE
Keywords: Bispectral index; Propofol; Sevoflurane; Sleep.
Affiliations: Department of Anesthesiology, The First Hospital of China Medical University, 155# Nanjingbei Street, Shenyang, China., Department of Anesthesiology, The First Hospital of China Medical University, 155# Nanjingbei Street, Shenyang, China. .

Abstract:  Despite major advances in anesthesia management and developments in anesthetic agents, postoperative sleep disturbances remain dissatisfactory for many patients. We hypothesized that propofol might have a subtle influence on sleep after thyroidectomy compared to sevoflurane. A randomized, single-blinded, controlled trial was conducted at the First Hospital of China Medical University from October 2014 to October 2015. One hundred and twenty-four patients undergoing thyroidectomy were enrolled and received sevoflurane (sevoflurane group) or propofol (propofol group) as anesthesia maintenance. Major assessments were made during the operation (different types of anesthetic management) and on the first postoperative night (sleep status). The primary outcome was postoperative sleep status, measured by the BIS-Vista monitor on the first night after surgery between propofol and sevoflurane groups. A total of 105 patients (79 women, 26 men; mean age 49 years; range 18-65 years) were included in the final study sample. All patients in both groups showed one of the five sleep patterns classified by this trial. The BIS-area under the curve was decreased, the sleep efficiency index was significantly increased, and the durations of postoperative sleep and sleep stage N3 were increased by 110.5 and 36.5 min per patient, respectively, in the propofol compared to the sevoflurane group. Propofol might preserve sleep time immediately after thyroidectomy. Clinical Trials.gov identifier: NCT 02146976. 

Retracted: No

PubPeer comments:
 Figure 2A in this paper shares a section of identical Bispectral Index recording with figure 2b in 10.1186 s12871-018-0485-9 ![file] , 
 #1 Thanks for professor John A Loadsmanu2019s careful reading our papers. I received the letter from editor several days ago. We checked the original data of this paper and found that there was no problem with this paper. We have sent the original data to the editor. Thanks again. ,
Long noncoding RNA NORAD promotes the progression of retinoblastoma by sponging miR-136-5p/PBX3 axis
Authors: Y-J Hao
B Wang
X-L Yang
X-L Gu
X-X Wang
J-F Sun
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA-NORAD; miR-136-5p; PBX3; retinoblastoma; ceRNA
Affiliations: Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China. .

Abstract:  Objective: The specific roles of long noncoding RNAs (lncRNAs) have been found in human cancers, including retinoblastoma (RB). However, the function of lncRNA-NORAD has not been reported in RB. Therefore, the regulatory mechanism of lncRNA-NORAD was investigated in the development of RB. Patients and methods: The experimental tissues were collected from 24 RB patients and 6 patients with ruptured globes. The average age of all patients was 2.78 years (range, 2 months to 11 years). The mRNA and protein expression was measured by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot analysis. The functional mechanism of NORAD was assessed by Cell Counting Kit-8 (CCK-8), transwell, and Dual-Luciferase reporter assays. Results: Upregulation of NORAD and downregulation of miR-136-5p were found in RB. Functionally, knockdown of NORAD and miR-136-5p overexpression restrained RB cell viability, invasion, and migration. In addition, NORAD acts as a ceRNA of miR-136-5p in RB. MiR-136-5p was found to directly target PBX3. Furthermore, knockdown of PBX3 inhibited the progression of RB. More importantly, the NORAD/miR-136-5p axis is involved in RB progression by mediating PBX3. Conclusions: LncRNA NORAD, serving as a ceRNA of miR-136-5p, accelerates RB progression by upregulation of PBX3. 

Retracted: Yes

PubPeer comments:
 Figure 6A. Two potential overlaps 1. Free REGO and PT NPs 2. A flipped REGO NPs and REGO-PT NPs, except that each has a single cell or a small cluster of cells that the other doesn t have, marked by broken ovals. ![file] ,
Newly identified motifs in Candida albicans Cdr1 protein nucleotide binding domains are pleiotropic drug resistance subfamily-specific and functionally asymmetric
Authors: Abdul Haseeb Shah
Alok Kumar Mondal
Mohammad Firoz Khan
Sobhan Sen
Atanu Banerjee
Rakesh Bhatnagar
Manpreet Kaur Rawal
Richard D Cannon
Brian C Monk
Rajendra Prasad
Ajay Kumar Saxena
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Candida albicans; ABC transporters; α-helical sequence motifs; Walker A sequence; protein function
Affiliations: School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India., School of Physical Sciences, Jawaharlal Nehru University, New Delhi, 110067, India., The Sir John Walsh Research Institute, University of Otago, Dunedin 9054, New Zealand., School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India.

Abstract:  An analysis of Candida albicans ABC transporters identified conserved related α-helical sequence motifs immediately C-terminal of each Walker A sequence. Despite the occurrence of these motifs in ABC subfamilies of other yeasts and higher eukaryotes, their roles in protein function remained unexplored. In this study we have examined the functional significance of these motifs in the C. albicans PDR transporter Cdr1p. The motifs present in NBD1 and NBD2 were subjected to alanine scanning mutagenesis, deletion, or replacement of an entire motif. Systematic replacement of individual motif residues with alanine did not affect the function of Cdr1p but deletion of the M1-motif in NBD1 (M1-Del) resulted in Cdr1p being trapped within the endoplasmic reticulum. In contrast, deletion of the M2-motif in NBD2 (M2-Del) yielded a non-functional protein with normal plasma membrane localization. Replacement of the motif in M1-Del with six alanines (M1-Ala) significantly improved localization of the protein and partially restored function. Conversely, replacement of the motif in M2-Del with six alanines (M2-Ala) did not reverse the phenotype and susceptibility to antifungal substrates of Cdr1p was unchanged. Together, the M1 and M2 motifs contribute to the functional asymmetry of NBDs and are important for maturation of Cdr1p and ATP catalysis, respectively. 

Retracted: No

PubPeer comments:
 Dear Sir, I appreciate your excellent work on retraction watch and I am one of the regular readers of this. Did you notice the images in this article? Figure 2. (A) Figure 6. (B) of Western blot and confocal microscopy images. Figure 3 4. (B) of Western blot and confocal microscopy images: CDR1 ,
MiRNA let-7g regulates skeletal myoblast motility via Pinch-2
Authors: S Cuvellier
I Dang
T Rivera Vargas
A Polesskaya
S Boudoukha
A Gautreau
J Kropp
Journal: FEBS Letters (2014)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Cell adhesion; Cell motility; Let-7g; PINCH-2; RNA-binding protein
Affiliations: CNRS FRE 3377, CEA Saclay, F-91191 Gif-sur-Yvette, France; Univ Paris-Sud, FRE 3377, F-91191 Gif-sur-Yvette, France; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA., CNRS FRE 3377, CEA Saclay, F-91191 Gif-sur-Yvette, France; Univ Paris-Sud, FRE 3377, F-91191 Gif-sur-Yvette, France., Centre de Recherche de Gif, Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR3082, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France., Inserm U1016, Institut Cochin, INSERM U1016, CNRS 8104, Université Paris Descartes, F-75014 Paris, France., CNRS FRE 3377, CEA Saclay, F-91191 Gif-sur-Yvette, France; Univ Paris-Sud, FRE 3377, F-91191 Gif-sur-Yvette, France. Electronic address: .

Abstract:  Post-transcriptional regulation of gene expression by RNA-binding proteins and by small non-coding RNAs plays an important role in cell biology. Our previous results show that in murine skeletal myoblasts, the expression of Pinch-2, a focal adhesion remodeling factor that regulates cell motility, is repressed by an RNA-binding protein IMP-2/Igf2bp2. We now show that the expression of Pinch-2 is also regulated by the miRNA let-7g. Let-7g and IMP-2 repress Pinch-2 expression independently of each other. A knock-down of let-7g leads to an increase in Pinch-2 expression, and to a decrease of cell motility, which can be reversed by a simultaneous knock-down of Pinch-2. We conclude that let-7g controls the motility of mouse myoblasts in cell culture by post-transcriptionally regulating the expression of Pinch-2. 

Retracted: No

PubPeer comments:
 Figure 4A. Much more similar than expected. https: imgur.com mpTVpsy ,
Ancestral Role of Ecdysis-Related Neuropeptides in Animal Life Cycle Transitions
Authors: Elisabeth Zieger
Andrew Calcino
Nicolas S M Robert
Andreas Wanninger
Journal: Current Biology (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: development; developmental transcriptomics; eclosion; evolution; invertebrates
Affiliations: Department of Evolutionary Biology, Integrative Zoology, University of Vienna, Althanstraße 14, Vienna 1090, Austria. Electronic address: ., Department of Neurosciences and Developmental Biology, University of Vienna, Althanstraße 14, Vienna 1090, Austria., Department of Evolutionary Biology, Integrative Zoology, University of Vienna, Althanstraße 14, Vienna 1090, Austria.

Abstract:  Ecdysis or molting evolved ∼535 mya in Ecdysozoa, the most diverse and species-rich animal superphylum.1 A cascade of ecdysis-related neuropeptides (ERNs) controls the innate behavioral programs required for cuticle shedding in some ecdysozoan lineages (e.g., arthropods)2-12 but is lacking in others (e.g., nematodes).13 We recently reported on the surprisingly ancient bilaterian origin of key ERNs, such as eclosion hormone (EH), crustacean cardioactive neuropeptide (CCAP), myoinhibitory peptide (MIP), bursicon alpha (Bursα), and bursicon beta (Bursβ).13,14 Thus, ERNs far predate the emergence of ecdysis, but the question as to their ancestral functions remains unresolved. Here, we compare the ERN toolkits and temporal expression profiles of six ecdysozoans (tardigrades, crustaceans, and insects), eight lophotrochozoans (planarians, annelids, and mollusks), and five deuterostomes (crinoids, sea urchins, and hemichordates). Our results show that the major, coordinated upregulation of ERNs always coincides with a transition between key life history stages, such as hatching in direct developers and metamorphosis in indirect developers. This implies that ERNs already played an ancestral role in the switch from embryonic or larval ontogeny to juvenile maturation in the last common ancestor of Nephrozoa. Consequently, the transcriptional signature of invertebrate life cycle transitions presented here was already in place in the Precambrian and was only secondarily co-opted into regulating the molting process at the dawn of Ecdysozoa. 

Retracted: No

PubPeer comments:
 Figure 5B. Much more similar than you would expect. https: imgur.com XgANB4o ,
Matrix rigidity controls endothelial differentiation and morphogenesis of cardiac precursors
Authors: Sergio Rey
Gregg L Semenza
Eun Hyun Ahn
Kshitiz
Maimon E Hubbi
Arnab Kundu
Deok-Ho Kim
Roselle M Abraham
Andre Levchenko
John Downey
Connie Chang
Junaid Afzal
Journal: Science Signaling (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Tissue development; regeneration; stem cells; proliferation; differentiation
Affiliations: Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.

Abstract:  Tissue development and regeneration involve tightly coordinated and integrated processes: selective proliferation of resident stem and precursor cells, differentiation into target somatic cell type, and spatial morphological organization. The role of the mechanical environment in the coordination of these processes is poorly understood. We show that multipotent cells derived from native cardiac tissue continually monitored cell substratum rigidity and showed enhanced proliferation, endothelial differentiation, and morphogenesis when the cell substratum rigidity closely matched that of myocardium. Mechanoregulation of these diverse processes required p190RhoGAP, a guanosine triphosphatase-activating protein for RhoA, acting through RhoA-dependent and -independent mechanisms. Natural or induced decreases in the abundance of p190RhoGAP triggered a series of developmental events by coupling cell-cell and cell-substratum interactions to genetic circuits controlling differentiation. 

Retracted: No

PubPeer comments:
 Identified by another reader. The two papers have their own threads https: pubpeer.com publications 3D3318A7C73D88EA1234C196C4F128 https: pubpeer.com publications 01494FDC36DDBAD1C246BC2E41093F *** ![file] , 
 An image in Figure 1N and Figure 1O appear to overlap, after rotation. Could the authors please check? *** ![file] , 
 The previous correction seems unrelated to the issues noted above. During the editing and revision process, explanations of the noncontiguous bands in immunoblotting data shown in Figure 6B and Figure 8D were inadvertently removed. Lines to more clearly indicate the noncontiguous samples have also been added to Figure 6B and Figure 8D. The updated portions of the legends appear below: Fig. 6. Panel B Immunoblotting analysis of GATA2 in scrKD and p190KD CDCs. Noncontiguous lanes from a single experiment are indicated by white lines. Fig. 8. Panel D GATA2 abundance in scrKD or p190KD CDCs cultured on the indicated substrata, with the indicated treatments, and for the indicated time periods. Noncontiguous lanes from a single experiment are indicated by black lines. Data are representative of two experiments. Starting 9 October 2012, the full text online (http: stke.sciencemag.org cgi content full 5 227 ra41) and the PDF (http: stke.sciencemag.org cgi reprint 5 227 ra41.pdf) have been corrected. ,
miR-20b reduces 5-FU resistance by suppressing the ADAM9/EGFR signaling pathway in colon cancer
Authors: Jindai Zhang
Qiang Fu
Suxia Luo
Jianguo Xie
Yonglei Zhang
Xiaobing Chen
Jing Cheng
Journal: Oncology Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: Chemoresistance; miR-20b; ADAM9; EGFR; 5-fluorouracil
Affiliations: Department of Gastrointestinal Surgery Center, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China., Department of Medical Oncology, Zhengzhou Central Hospital, Zhengzhou, Henan 450007, P.R. China., Department of Digestion and Medical Oncology, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.

Abstract:  Chemoresistance is a major obstacle to cancer therapy including that of colon cancer (CC). Although the dysregulation of many miRNAs has been implicated in 5-fluorouracil (5-FU) resistance in CC cells, the specific role of miR-20b in chemoresistance has not been documented. In the present study, we first determined the expression of miR-20b by RT-PCR and the levels of a disintegrin and metalloprotease 9 (ADAM9) and epidermal growth factor receptor (EGFR) by western blotting in CC and adjacent non-cancerous tissues from 5-FU-sensitive or -resistant CC patients. Subsequently, 5-FU-sensitive (HCT116) and -resistant (HCT116-R) cells were obtained, and the levels of miR-20b, ADAM9 and EGFR were detected. Meanwhile, the 5-FU resistance of the cells was examined by assessing cell viability (by MTT assay) and apoptosis (by flow cytometry). After transfection of miR-20b into HCT116-R cells, drug resistance was reexamined. We then confirmed the relationship between miR-20b and ADAM9 by luciferase reporter assay. Finally, 5-FU resistance in HCT116 and HCT116-R cells was compared after transfection with miR-20b. Our results showed that miR-20b was expressed at lower levels in the 5-FU-resistant tissues and cells than in the 5-FU-sensitive tissues and cells. The opposite was the case for expression of ADAM9 and EGFR. In addition, we demonstrated that ADAM9 is a direct target of miR-20b and that miR-20b decreased the 5-FU resistance of HCT116-R cells. Our findings suggest that miR-20b reduces 5-FU resistance to induce apoptosis in vitro by suppressing ADAM9/EGFR in CC cells. 

Retracted: No

PubPeer comments:
 In the flow cytometry dot plots in Figure 2B,C, several areas of two different plots are surprisingly similar. ![file] , 
 #1 Good cancellation! ![file] ,
DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress
Authors: Zhiqin Wang
Peng Jin
Ying Cheng
Hao Wu
Li Chen
Luoxiu Huang
Bing Yao
Beisha Tang
Dahua Chen
Yujing Li
Wenxin Zhang
Journal: Nature Communications (2017)
Discipline: Multidisciplinary
Keywords: Chemical modifications; DNA molecules; 5-methylcytosine; 5-hydroxymethylcytosine; N(6)-methyladenine
Affiliations: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA., Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China., Department of Health Outcomes Research and Policy, Harrison School of Pharmacy, Auburn University, Auburn, AL, 36849, USA., State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China., Department of Biostatistics and Bioinformatics, Emory University School of Public Health, Atlanta, GA, 30322, USA., Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA. .

Abstract:  Chemical modifications on DNA molecules, such as 5-methylcytosine and 5-hydroxymethylcytosine, play important roles in the mammalian brain. A novel DNA adenine modification, N(6)-methyladenine (6mA), has recently been found in mammalian cells. However, the presence and function(s) of 6mA in the mammalian brain remain unclear. Here we demonstrate 6mA dynamics in the mouse brain in response to environmental stress. We find that overall 6mA levels are significantly elevated upon stress. Genome-wide 6mA and transcriptome profiling reveal an inverse association between 6mA dynamic changes and a set of upregulated neuronal genes or downregulated LINE transposon expression. Genes bearing stress-induced 6mA changes significantly overlap with loci associated with neuropsychiatric disorders. These results suggest an epigenetic role for 6mA in the mammalian brain as well as its potential involvement in neuropsychiatric disorders. 

Retracted: No

PubPeer comments:
 I suggest to add the following papers into the discussion in addition to (13, 14): 1. Linker W, Lu00f6ffler M, Schneider F. Uridine, but not cytidine can sustain growth of Ehrlich ascites tumor cells in glucose-deprived medium with altered proliferation kinetics. Eur J Cell Biol. 1985 Mar;36(2):176-81. [PMID: 3996430] . 2. Lu00f6ffler M, Wenzel A, Schneider F. Cytokinetic studies on the switch from glucose to uridine metabolism, and vice versa, of Ehrlich ascites tumour cells in vitro. Cell Tissue Kinet. 1987 Mar;20(2):181-90. doi: [10.1111 j.1365-2184.1987.tb01097.x] . [PMID: 3607842] . ,
RETRACTED ARTICLE: A novel microRNA identified in hepatocellular carcinomas is responsive to LEF1 and facilitates proliferation and epithelial-mesenchymal transition via targeting of NFIX
Authors: Jinxia Wang
Xu Guo
Shengping Li
Min Liu
Hongxia Fan
Huijie Gao
Yaqi Hu
Yankun Liu
Xiangyang Nong
Hua Tang
Xi Yang
Journal: Oncogenesis (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Hepatocellular carcinoma; miRNA; miR-HCC1; cell proliferation; migration
Affiliations: Tianjin Life Science Research Center and Department of Pathogen Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China., The Cancer Institute, Tangshan People's Hospital, 063001, Tangshan, China., Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, 510060, Guangzhou, China., Tianjin Life Science Research Center and Department of Pathogen Biology, Collaborative Innovation Center of Tianjin for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China. .

Abstract:  Hepatocellular carcinoma (HCC) is one of the most prevalent cancers. It has been demonstrated that various cellular microRNAs (miRNAs) play an important role in HCC development. Here, we analyzed the miRNA profile in HCC tissues by Solexa sequencing, and we identified a novel microRNA, miR-HCC1, which is upregulated in HCC tissues. Further experiments showed that miR-HCC1 promoted HCC cell proliferation in vivo and in vitro, and migration and invasion resulting from the epithelial-mesenchymal transition (EMT) process. Nuclear factor I/X (NFIX), which inhibited cell proliferation, migration and invasion in HCC cells, was identified as a direct and functional target of miR-HCC1. Furthermore, lymphoid enhancer binding factor 1 (LEF1), a transcription factor, was shown to bind the promoter of miR-HCC1 and activate its expression. Collectively, these results indicate that LEF1-upregulated miR-HCC1 functions as an oncogene through the negative regulation of NFIX expression, which links the LEF1/miR-HCC1/NFIX axis to contribute to cell proliferation, migration and invasion of HCC cells and could provide novel insights into miRNA function and hepatocarcinogenesis and potential biomarkers for HCC. 

Retracted: Yes

PubPeer comments:
 ![file] , 
 #1 Dear colleague, Thank you for bringing to our attention on this figure. Myself Biju George is the first author of the paper. I have carried out these experiments and have also assembled the figures of the manuscript. I apologize for this inadvertent error that has occurred during figure assembly. The two panels showing individual blots with the D262A and K286A are highly identical; hence this mistake happened while assembling the figures. We shall submit the author correction along with the raw images to journal very soon. This inadvertent error does not in any way alter either the interpretations or the conclusions drawn in the manuscript. We will post the link here as soon as it is available. Thank you. Biju ,
Baicalin alleviates 6-hydroxydopamine-induced neurotoxicity in PC12 cells by down-regulation of microRNA-192-5p
Authors: Xiaoyang Liu
Yao Fu
Mingyang Kang
Libo Wang
Chunyang Kang
Jian Gao
Journal: Brain Research (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Baicalin; MDM-2/p53; PI3K/AKT; Parkinson's disease; miR-192-5p.
Affiliations: Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China., Department of Spine Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130000, China., Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China., Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China. Electronic address: .

Abstract:  Parkinson's disease (PD), which is caused by neurodegenerative disorder, has no effective treatment until now. Baicalin was reported to have neuroprotective effects. Hence, we investigated the effects of baicalin on PD in an in vitro cell model by using 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rat pheochromocytoma PC12 cells. PC12 cells were stimulated by 6-OHDA and were treated with baicalin and/or transfected with miR-192-5p mimic or negative control (NC). Cell viability and apoptosis were examined by Cell Counting Kit-8 assay and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) analysis, respectively. The expression of p62, ratio of light chain (LC)3-II/LC3-I, miR-192-5p was detected by qRT-PCR. All protein expression levels were analyzed by western blot. We found that 6-OHDA significantly inhibited cell viability, induced apoptosis and autophagy, while baicalin reversed the results led by 6-OHDA. Moreover, baicalin negatively regulated expression of miR-192-5p. Under baicalin treatment, transfection with miR-192-5p mimic decreased cell viability and induced apoptosis and autophagy in 6-OHDA-treated cells compared with NC. In addition, the phosphorylation of phosphatidylinositol 3'-kinase (PI3K) and protein kinase B (AKT) was statistically down-regulated by baicalin then thereafter reversed by miR-192-5p mimic. Baicalin reduced 6-OHDA-induced cell injury through down-regulation of miR-192-5p, as well as regulation of PI3K/AKT and MDM-2/p53 signal pathways. 

Retracted: No

PubPeer comments:
 Fig 4F: ![file] The western blots that comprise the experimental data in this paper all have this leaping sardine appearance associated with the  Tadpole Papermill . ,
Gene disruption of the DNA topoisomerase IB small subunit induces a non-viable phenotype in the hemoflagellate Leishmania major
Authors: Carlos García-Estrada
Yolanda Pérez-Pertejo
Rosa M Reguera
Rafael Balaña-Fouce
Journal: BMC Microbiology (2008)
Discipline: MICROBIOLOGY
Keywords: Leishmania; DNA topoisomerase IB; null mutants; selection markers; camptothecin cytotoxicity
Affiliations: Departamento de Farmacología y Toxicología (INTOXCAL), Universidad de León, Campus de Vegazana s/n; 24071 León, Spain. 

Abstract:  Background: The unusual heterodimeric leishmanial DNA topoisomerase IB consists of a large subunit containing the phylogenetically conserved "core" domain, and a small subunit harboring the C-terminal region with the characteristic tyrosine residue in the active site. RNAi silencing of any of both protomers induces a non-viable phenotype in the hemoflagelate Trypanosoma brucei. Unfortunately, this approach is not suitable in Leishmania where gene replacement with an antibiotic marker is the only approach to generate lack-of-function mutants. In this work, we have successfully generated null mutants in the small subunit of the L. major DNA topoisomerase IB using two selection markers, each conferring resistance to hygromycin B and puromycin, respectively. Results: We have successfully replaced both topS loci with two selection markers. However, to achieve the second transfection round, we have had to rescue the null-homozygous with an episomal vector carrying the Leishmania major topS gene. Phenotypic characterization of the L. major rescued strain and a L. major strain, which co-overexpresses both subunits, shows few differences in DNA relaxation and camptothecin cytotoxicity when it was compared to the wild-type strain. Studies on phosphatidylserine externalization show a poor incidence of camptothecin-induced programmed cell death in L. major, but an effective cell-cycle arrest occurs within the first 24 h. S-Phase delay and G2/M reversible arrest was the main outcome at lower concentrations, but irreversible G2 arrest was detected at higher camptothecin pressure. Conclusion: Results obtained in this work evidence the essentiality of the topS gene encoding the L. major DNA topoisomerase IB small subunit. Reversibility of the camptothecin effect points to the existence of effective checkpoint mechanisms in Leishmania parasites. 

Retracted: No

PubPeer comments:
 Figure 8 and Figure 9. * Boxes of the same color focus attention to some quadrants that look remarkably and unexpectedly similar. Reported to the Editor in July 2015, but no action as of today. ![file] , 
 Dear Sir Thanks for the comments made to the article. You can see attached a print out of the mail sent in due form to the editor (Alexandros Hussein) of BMC microbiology on December 21th 2016 replying to the questions made to these very queries. ![file] sincerely ,