PReD-Bench/PRed-Bench huggingface dataset:
Differential regulation of Wnt/beta-catenin signaling by Liver X Receptors in Schwann cells and oligodendrocytes
Authors: Charbel Massaad
Delphine Meffre
Philippe Liere
Julien Grenier
Ghjuvan&#x27;Ghjacumu Shackleford
Joelle Makoukji
Journal: Biochemical Pharmacology (2013)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Oxysterols; Cholesterol homeostasis; Neurodegenerative disorders; Myelinating glial cells; Central nervous system
Affiliations: University Paris Descartes, UMR 8194 CNRS, 45 rue des Saints-Pères, 75270, Paris Cedex 6, France.

Abstract:  Oxysterols are reactive molecules generated by the oxidation of cholesterol. Their implication in cholesterol homeostasis and in the progression of neurodegenerative disorders is well known. Here, we study the role of oxysterols and their nuclear receptors, Liver X Receptor (LXR), in myelinating glial cells of the central and peripheral nervous systems. First, we show by gas chromatography/mass spectrometry that the brain, sciatic nerve, oligodendrocytes and Schwann cells contain 24(S)-hydroxycholesterol, 25-hydroxycholesterol (25-OH) and 27-hydroxycholesterol, and they express their biosynthetic enzymes. We observed a differential effect of 25-OH toward myelin genes (MPZ and PMP22) expression: 25-OH inhibits MPZ and PMP22 in Schwann cell line but not in oligodendrocyte cell line. Importantly, the invalidation of LXR in mice enhanced MPZ and PMP22 transcripts expression in the sciatic nerve, but inhibited their expression in the brain. We have previously reported that Wnt signaling pathway is crucial for myelin gene expression. We show that the transcripts of Wnt components (Disheveled, TCF3, beta-catenin) are strongly repressed by oxysterols in Schwann cells but are activated in oligodendrocytes. Furthermore, we show by immunofluorescent labeling that beta-catenin is re-localized on the level of the Golgi apparatus of Schwann cells after incubation with 25-OH. We did not observe such an unusual localization of beta-catenin in oligodendrocytes. Our findings reveal a complex cross-talk between LXR and Wnt/beta-catenin pathway in myelinating glial cells. 

Retracted: No

PubPeer comments:
 Data in Biochem Pharmacol.u00a02013 Jul 1;86(1):106-14 much more similar than you would expect to data in J Neurosci.u00a02011 Jun 29;31(26):9620-9. https: imgur.com 2SlaRb6 https: imgur.com Q4JiGIq , 
 #1 The Biochemical Pharmacology article (2013) is the direct continuation of the findings that we published in 2011 in the Journal of Neuroscience article. Three panels, out of 39, of the Biochem Pharmacol article were reproduced from our manuscript that we published in the J Neurosci. article. We own the copyright for the latter. We decided to use these panels as the starting points of the work developed in the Biochem Pharmacol to make a comparison of data between central and peripheral nervous system. We cited our article published in the J. Neurosci. twice in the Biochem Pharmacol (p110 and p113), but did not specify this reference in the fig legends. We are in contact with the editor in chief of the Biochem Pharmacol. The authors ,
RNA-binding protein HuD controls insulin translation
Authors: Sarah S Subaran
Hideyuki Okano
Rafael de Cabo
Wook Kim
Olga D Carlson
Kumiko Tominaga
Josephine M Egan
Eun Kyung Lee
Myriam Gorospe
Wado Akamatsu
Nora I Perrone-Bizzozero
Evi M Mercken
Rohit N Kulkarni
Jennifer L Martindale
Xiaoling Yang
Journal: Molecular Cell (2012)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: HuD; pancreatic β cells; insulin receptor pathway; preproinsulin mRNA; translation
Affiliations: Laboratory of Molecular Biology and Immunology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.

Abstract:  Although expression of the mammalian RNA-binding protein HuD was considered to be restricted to neurons, we report that HuD is present in pancreatic β cells, where its levels are controlled by the insulin receptor pathway. We found that HuD associated with a 22-nucleotide segment of the 5' untranslated region (UTR) of preproinsulin (Ins2) mRNA. Modulating HuD abundance did not alter Ins2 mRNA levels, but HuD overexpression decreased Ins2 mRNA translation and insulin production, and conversely, HuD silencing enhanced Ins2 mRNA translation and insulin production. Following treatment with glucose, HuD rapidly dissociated from Ins2 mRNA and enabled insulin biosynthesis. Importantly, HuD-knockout mice displayed higher insulin levels in pancreatic islets, while HuD-overexpressing mice exhibited lower insulin levels in islets and in plasma. In sum, our results identify HuD as a pivotal regulator of insulin translation in pancreatic β cells. 

Retracted: No

PubPeer comments:
 In this manuscript, beta-actin bands in Figure 1D and 1K are similar. When sized-adjusted (column 3), they look more similar. Pay attention to the identical shadows underneath the beta-actin bands (red arrows). Column 1: original figures Column 2: enlarged original figures Column 3: original figure ![file] ,
Leptin mediates postprandial increases in body temperature through hypothalamus–adrenal medulla–adipose tissue crosstalk
Authors: Yunfan Yang
Xiruo Li
Aviva Rabin-Court
Rachel J Perry
Jianying Dong
Xiaoyong Yang
Kun Lyu
Hua Qing
Andrew Wang
Gerald I Shulman
Journal: Journal of Clinical Investigation (2020)
Discipline: CLINICAL MEDICINE
Keywords: Endocrinology; Leptin; Metabolism.
Affiliations: Departments of Internal Medicine., Cellular & Molecular Physiology., Comparative Medicine, and., Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.

Abstract:  Meal ingestion increases body temperature in multiple species, an effect that is blunted by obesity. However, the mechanisms responsible for these phenomena remain incompletely understood. Here we show that refeeding increases plasma leptin concentrations approximately 8-fold in 48-hour-fasted lean rats, and this normalization of plasma leptin concentrations stimulates adrenomedullary catecholamine secretion. Increased adrenal medulla-derived plasma catecholamines were necessary and sufficient to increase body temperature postprandially, a process that required both ﻿fatty acids generated from adipose tissue lipolysis and β-adrenergic activation of brown adipose tissue (BAT). Diet-induced obese rats, which remained ﻿relatively hyperleptinemic while fasting, did not exhibit fasting-induced reductions in temperature. To examine the impact of feeding-induced increases in body temperature on energy balance, we compared rats fed chronically by either 2 carbohydrate-rich boluses daily or a continuous ﻿isocaloric intragastric infusion. Bolus feeding increased body temperature and reduced weight gain compared with continuous feeding, an effect abrogated by treatment with atenolol. In summary, these data demonstrate that leptin stimulates a hypothalamus-adrenal medulla-BAT axis, which is necessary and sufficient to induce lipolysis and, as a result, increase body temperature after refeeding. 

Retracted: No

PubPeer comments:
 The only problem is that leptin is not a thermogenic hormone (see PMID: 31774114). , 
 #1 https: journals.physiology.org doi full 10.1152 ajpregu.00045.2016 https: www.ncbi.nlm.nih.gov pmc articles PMC4216404 The issue whether leptin is a thermogenic hormone or not is still unclear due to conflicting results. Hence, additional studies are welcomed. I fail to see the issue with the mentioned paper by the first post above. ,
Static mechanical stress induces apoptosis in rat endplate chondrocytes through MAPK and mitochondria-dependent caspase activation signaling pathways
Authors: Tiansheng Zheng
Dechao Kong
Xiaojian Cao
Xiang Li
Jiahu Fang
Ming Zhang
Daode Wang
Shihao Du
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Mechanical stress; cartilaginous endplate chondrocytes; apoptosis; signaling pathways; rat cervical endplate chondrocytes
Affiliations: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Abstract:  Mechanical stress has detrimental effects on cartilaginous endplate chondrocytes due to apoptosis in vivo and in vitro. In this study, we investigated the possible apoptosis signaling pathways induced by mechanical stress in cultured rat cervical endplate chondrocytes. Static mechanical load significantly reduced cell viability in a time- and load-dependent manner, as demonstrated by the Cell Counting Kit-8 (CCK-8) assay. Chondrocyte apoptosis induced by mechanical stress was confirmed by annexin V/propidium iodide (PI) staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Western blot analysis revealed that static load-induced chondrocyte apoptosis was accompanied by increased phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (MAPK). The loss of mitochondrial membrane potential (ΔΨm), increased Cytochrome c release, and activated Caspase-9 and Caspase-3, indicating that the mitochondrial pathway is involved in mechanical stress-induced chondrocyte apoptosis. Treatment with inhibitors of JNK (SP600125), p38 MAPK (SB203580), and ERK (PD98059) prior to mechanical stimulation reversed both the static load-induced chondrocyte apoptosis and the activation of JNK, p38 MAPK, and ERK. Taken together, the data presented in this study demonstrate that mechanical stress induces apoptosis in rat cervical endplate chondrocytes through the MAPK-mediated mitochondrial apoptotic pathway. 

Retracted: No

PubPeer comments:
 Figure 3A. * Red boxes: The SP600125 and S B203580 panels appear to show the same plots, but differ in gated percentages. Reported to the journal in October 2015, but no update as of today. ![file] , 
 An additional finding in Figure 4, not reported in 2015. * Cyan boxes: The 0.5 MPa and ).5 MPa+PD panels appear to overlap in the green channel image, but not in the red channel. ![file] ,
Quercetin 7-rhamnoside reduces porcine epidemic diarrhea virus replication via independent pathway of viral induced reactive oxygen species
Authors: Jae Hyoung Song
Hwa Jung Choi
Jae Kwon Shim
Journal: Virology Journal (2011)
Discipline: MICROBIOLOGY
Keywords: quercetin 7-rhamnoside; antiviral activity; cytopathic effects; DNA fragmentation; reactive oxygen species
Affiliations: Department of Herbal Resources, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan 570-749, South Korea.

Abstract:  Background: On the base of our previous study we were observed relevant studies on the hypothesis that the antiviral activity of quercetin 7-rhamnoside (Q7R), a flavonoid, won't relate ability of its antioxidant. Methods: We were investigated the effects of Q7R on the cytopathic effects (CPE) by CPE reduction assay. Production of DNA fragment and reactive oxygen species (ROS) induced by PEDV infection were studied using DNA fragmentation assay and flow cytometry. Results: In the course of this study it was discovered that Q7R is an extremely potent compound against PEDV. The addition of Q7R to PEDV-infected Vero cells directly reduced the formation of a visible cytopathic effect (CPE). Also, Q7R did not induce DNA fragmentation. Furthermore, ROS increased the infection of PEDV, which was strongly decreased by N-acetyl-L-cysteins (NAC). However, the increased ROS was not decreased by Q7R. Antiviral activity of antioxidants such as NAC, pyrrolidine dithiocarbamate (PDTC), and the vitamin E derivative, trolox, were hardly noticed. Conclusions: We concluded that the inhibition of PEDV production by Q7R is not simply due to a general action as an antioxidants and is highly specific, as several other antioxidants (NAC, PDTC, trolox) are inactive against PEDV infection. 

Retracted: No

PubPeer comments:
null, 
null, 
null, 
null, 
null, 
 Still nothing on this paper? https: retractionwatch.com 2018 12 13 anversa-cardiac-stem-cell-lab-earns-13-retractions ,
RETRACTED: Ultrasound image guided lateral cervical approach to stellate ganglion block for cervical headache
Authors: Xiaokun Li
Enrui Zheng
Qian Yu
Xiuju Ding
Journal: Neuroscience Letters (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Nerve block; Stellate ganglia; Ultrasound.
Affiliations: Department of Anesthesiology, Weifang People's Hospital, Weifang, Shandong, 261000, China., Department 1 of Anesthesiology, Weifang Hospital of Traditional Chinese Medicine, Weifang, Shandong, 261041, China., Pain Department, Weifang People's Hospital, Weifang, Shandong, 261000, China., Ultrasound Department of Weifang People's Hospital, Weifang, Shandong, 261000, China. Electronic address: .

Abstract:  Objective: To explore the feasibility and safety of real-time ultrasound-guided transcervical lateral stellate ganglion block. Methods: From September 2017 to December 2018, 80 cases of cervical headache were diagnosed by high-frequency ultrasound on the lateral cervical region, and evaluated at the level of the transverse process of cervical vertebrae 6 and 7. Risk factors for the ganglia. Choose a safe path and guide puncture and drug injection in real time. Results: The lateral approach of horizontal C6 and C7 transverse processes in 80 cases was explored. There are risk factors on the 32-sided puncture path, in which the inferior thyroid artery accounts for 34.4 % (11/32), the jugular vein accounts for 31.2 % (10/32), and the vertebral arteriovenous accounts for 12.5 % (4/32) The other arteries accounted for 21.9 % (7/32). The puncture was completed in 79 cases, and one patient gave up the puncture because of risk factors in the horizontal puncture path of C6 and C7. Horner syndrome occurred in 79 cases within 10 min after puncture. There were 4 cases (5.1 %) of minor side effects, including hoarseness in 2 cases, numbness in upper limbs and dizziness in 1 case, all of which resolved on their own. The VAS score of 79 cases before block (8.9 ± 0.9) points and 0.5h VAS score (5.7 ± 2.1) points after block were significantly lower than those before block (t = 13.154, P = 0.003); 1dVAS score (5.3 ± 2.5) after block was significantly lower than that before block (t = 12.626, P = 0.002). Conclusion: High-frequency ultrasound guided stellate ganglion block in lateral cervical approach in real time has a high success rate and the method is safe. 

Retracted: Yes

PubPeer comments:
 You might be interested in the crystal structure of the compound corresponding to the JCPDS card 48-0083 solved in 2019 and leading to a drastic change of the chemical formula: http: scripts.iucr.org cgi-bin citedin?sk3716  A quarter of a century after its synthesis and with 200 papers based on its use, `Co(CO3)0.5(OH)u00b70.11H2Ou2032 proves to be Co6(CO3)2(OH)8u00b7H2O from synchrotron powder diffraction data ![file] ,
The MyoD-inducible p204 protein overcomes the inhibition of myoblast differentiation by Id proteins
Authors: Peter Lengyel
Chuan-ju Liu
Bo Ding
Hong Wang
Journal: Molecular and Cellular Biology (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p204 protein; myoblast fusion; differentiation; MyoD protein; Id proteins
Affiliations: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8024, USA.

Abstract:  The murine p204 protein level is highest in heart and skeletal muscle. During the fusion of cultured myoblasts to myotubes, the p204 level increases due to transcription dependent on the muscle-specific MyoD protein, and p204 is phosphorylated and translocated from the nucleus to the cytoplasm. p204 overexpression accelerates myoblast fusion in differentiation medium and triggers this process even in growth medium. Here we report that p204 is required for the differentiation of C2C12 myoblasts. We propose that it enables the differentiation, at least in part, by overcoming the inhibition of the activities of the MyoD and E47 proteins by the Id proteins: Id1, Id2, and Id3. These are known to inhibit skeletal muscle differentiation by binding and blocking the activity of MyoD, E12/E47, and other myogenic basic helix-loop-helix (bHLH) proteins. Our hypothesis is based on the following findings. (i) A decrease in the p204 level in C2C12 myoblasts by antisense RNA (a) increased the level of the Id2; (b) inhibited the MyoD-, E12/E47-, and other bHLH protein-dependent accumulation of the muscle-specific myosin heavy-chain protein; and (c) inhibited the fusion of myoblasts to myotubes in differentiation medium. (ii) p204 bound to the Id proteins in vitro and in vivo. (iii) In the binding of p204 to Id2, the b segment of p204 and the HLH segment of Id2 were involved. (iv) Addition of p204 overcame the inhibition by the Id proteins of the binding of MyoD and E47 to DNA in vitro. (v) Overexpression of p204 in myoblasts (a) decreased the level of the Id proteins, even in a culture in growth medium, and (b) overcame the inhibition by the Id proteins of MyoD- and E47 dependent transcription and also overcame the inhibition by Id2 of the fusion of myoblasts to myotubes. 

Retracted: No

PubPeer comments:
 Figure 1A. Much more similar than you would expect. https: imgur.com bVVOWNQ ,
c-SRC mediates neurite outgrowth through recruitment of Crk to the scaffolding protein Sin/Efs without altering the kinetics of ERK activation
Authors: Konstantina Alexandropoulos
Jan Sap
Liang-Tung Yang
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: SRC family kinases; neurite extension; epidermal growth factor; endogenous SRC; receptor-protein-tyrosine phosphatase alpha
Affiliations: Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA.

Abstract:  SRC family kinases have been consistently and recurrently implicated in neurite extension events, yet the mechanism underlying their neuritogenic role has remained elusive. We report that epidermal growth factor (EGF) can be converted from a non-neuritogenic into a neuritogenic factor through moderate activation of endogenous SRC by receptor-protein-tyrosine phosphatase alpha (a physiological SRC activator). We show that such a qualitative change in the response to EGF is not accompanied by changes in the extent or kinetics of ERK induction in response to this factor. Instead, the pathway involved relies on increased tyrosine phosphorylation of, and recruitment of Crk to, the SRC substrate Sin/Efs. The latter is a scaffolding protein structurally similar to the SRC substrate Cas, tyrosine phosphorylation of which is critical for migration in fibroblasts and epithelial cells. Expression of a dominant negative version of Sin interfered with receptor-protein-tyrosine phosphatase alpha/EGF- as well as fibroblast growth factor-induced neurite outgrowth. These observations uncouple neuritogenic signaling in PC12 cells from sustained activation of ERK kinases and for the first time identify an effector of SRC function in neurite extension. 

Retracted: No

PubPeer comments:
 **Fig. 3B Threep groups, including untreated vector group, vector with EGF treatment group, RPTPu03b1Y798F with EGF and PD 98059 treatment group, had unexpected similar images scope.** ![file] ,
Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB
Authors: Peggy P Hsu
Andrew L Markhard
Shomit Sengupta
Dos D Sarbassov
Alex F Bagley
David M Sabatini
Joon-Ho Sheen
Siraj M Ali
Journal: Molecular Cell (2006)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: rapamycin; mTORC1; mTORC2; FKBP12; Akt/PKB
Affiliations: Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.

Abstract:  The drug rapamycin has important uses in oncology, cardiology, and transplantation medicine, but its clinically relevant molecular effects are not understood. When bound to FKBP12, rapamycin interacts with and inhibits the kinase activity of a multiprotein complex composed of mTOR, mLST8, and raptor (mTORC1). The distinct complex of mTOR, mLST8, and rictor (mTORC2) does not interact with FKBP12-rapamycin and is not thought to be rapamycin sensitive. mTORC2 phosphorylates and activates Akt/PKB, a key regulator of cell survival. Here we show that rapamycin inhibits the assembly of mTORC2 and that, in many cell types, prolonged rapamycin treatment reduces the levels of mTORC2 below those needed to maintain Akt/PKB signaling. The proapoptotic and antitumor effects of rapamycin are suppressed in cells expressing an Akt/PKB mutant that is rapamycin resistant. Our work describes an unforeseen mechanism of action for rapamycin that suggests it can be used to inhibit Akt/PKB in certain cell types. 

Retracted: No

PubPeer comments:
 Figure 3B. https: imgur.com nE7eDoT , 
 Thank you for your comment. This 14-year-old paper shows that in addition to inhibiting mTORC1, prolonged rapamycin treatment unexpectedly disrupts mTORC2 and thus inhibits the phosphorylation of Akt, the canonical mTORC2 substrate. This finding has been widely replicated and is the basis for the current search by industry for selective mTORC1 inhibitors that spare mTORC2. Hydrophis Spiralis points to two gel splices in the blot for mTOR in the HeLa cell samples in Figure 3B. Without examining the original films, which are stored in an offsite repository, I cannot be sure why the splices were made. The usual reason is because we decided to remove intervening samples that were not relevant to the final figure (for example, additional rapamycin treatment times). Not all blots will have splice junctions because often we reran the gels for certain blots because there were issues with the processing of the gel or the immunoblot, which provided an opportunity to analyze only the samples relevant to the final figure. As was common practice in 2006, the splice junctions are not indicated by lines. Please note that the presence of a gel splice has no impact on the validity of the data or the conclusions we made, which have been confirmed by the community, as noted above. Best wishes, David M. Sabatini ,
Impaired micro-RNA pathways diminish osteoclast differentiation and function
Authors: Keith A Hruska
Toshifumi Sugatani
Journal: Journal of Biological Chemistry (2009)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: miRNAs; DGCR8; Dicer; Ago2; osteoclast differentiation

Abstract:  Micro-RNAs (miRNAs) are important in regulating cell fate determination because many of their target mRNA transcripts are engaged in cell proliferation, differentiation, and apoptosis. DGCR8, Dicer, and Ago2 are essential factors for miRNA homeostasis. Here we show that these three factors have critical roles in osteoclast differentiation and function. Gene silencing of DGCR8, Dicer, or Ago2 by small interfering RNA revealed global inhibition of osteoclast transcription factor expression and function, decreased osteoclastogenesis, and decreased bone resorption in vitro. In vivo, CD11b(+)-cre/Dicer-null mice had mild osteopetrosis caused by decreased osteoclast number and bone resorption. These results suggest that miRNAs play important roles in differentiation and function of osteoclasts in vitro and in vivo. We found a novel mechanism mediating these results in which PU.1, miRNA-223, NFI-A, and the macrophage colony-stimulating factor receptor (M-CSFR) are closely linked through a positive feedback loop. PU.1 stimulates miRNA-223 expression, and this up-regulation is implicated in stimulating differentiation and function of osteoclasts through negative regulation of NFI-A levels. Down-regulation of NFI-A levels is important for expression of the M-CSFR, which is critical for osteoclast differentiation and function. NFI-A overexpression decreased osteoclast formation and function with down-regulation of M-CSFR levels. Forced expression of the M-CSFR in M-CSF-dependent bone marrow macrophages from Dicer-deficient mice rescued osteoclast differentiation with up-regulation of PU.1 levels. Our studies provide new molecular mechanisms controlling osteoclast differentiation and function by the miRNA system and specifically by miRNA-223, which regulates NFI-A and the M-CSFR levels. 

Retracted: No

PubPeer comments:
 Fig. 3D: More similar than expected ![file] ,
Aluminum inclusion macrophagic myofasciitis: a recently identified condition
Authors: Romain K Gherardi
François-Jérôme Authier
Journal: Immunology and Allergy Clinics of North America (2003)
Discipline: IMMUNOLOGY
Keywords: aluminum hydroxide; intramuscular injection; long-term adverse effects; vaccine adjuvants; public health
Affiliations: Muscle and Nerve Group, Henri Mondor University Hospital, Créteil, France. 

Abstract:  The authors conclude that the persistence of aluminum hydroxide at the site of intramuscular injection is a novel finding which has an exact significance that remains to be established fully. It seems mandatory to evaluate possible long-term adverse effects induced by this compound, because this issue has not been addressed (in the past, aluminum hydroxide was believed to be cleared quickly from the body). If safety concerns about the long-term effects of aluminum hydroxide are confirmed, novel and alternative vaccine adjuvants to rescue vaccine-based strategies should be proposed to ensure the enormous benefit for public health that these vaccines provide worldwide. 

Retracted: No

PubPeer comments:
 Figures 3D and 4A. Much more similar than expected. ![file] ,
The Yin Yang 1 transcription factor associates with ribonucleoprotein (mRNP) complexes in the cytoplasm of Xenopus oocytes
Authors: Nick Ovsenek
Andrew Ficzycz
Journal: Journal of Biological Chemistry (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: YY1; transcription factor; gene regulation; oogenesis; embryonic development
Affiliations: Department of Anatomy and Cell Biology, College of Medicine, 107 Wiggins Road, University of Saskatchewan, Saskatoon SK S7N 5E5, Canada.

Abstract:  Yin Yang 1 (YY1) is a multifunctional transcription factor that activates, represses, or initiates transcription of a diverse assortment of genes. Previous studies suggest a role for YY1 in cellular growth and differentiation, but its biological function during development of the vertebrate oocyte or embryo remains to be determined. We recently showed that YY1 is abundantly expressed throughout oogenesis and early embryonic stages of Xenopus, but it is sequestered in the cytoplasm and does not function directly in transcriptional regulation. In the present study we used a series of biochemical analyses to explore the potential function of YY1 in the oocyte cytoplasm. YY1 was isolated from oocyte lysates by oligo(dT)-cellulose chromatography, suggesting that it associates with maternally expressed mRNA in vivo. RNA mobility shift assays demonstrate that endogenous YY1 binds to labeled histone mRNA. Size exclusion chromatography of oocyte lysates revealed that YY1 exists in high molecular mass complexes in the range of 480 kDa. Destruction of endogenous RNA by RNase treatment of lysates, abolished the binding of YY1 to oligo(dT)-cellulose and resulted in redistribution from 480-kDa complexes to the monomeric form. Microinjection of RNase directly into the cytoplasm released YY1 from 480-kDa complexes and unmasked its DNA-binding activity, but did not promote translocation to the nucleus. These results provide evidence that YY1 is a component of ribonucleoprotein (mRNP) complexes in the Xenopus oocyte, indicating a novel function for YY1 in the storage or metabolism of maternal transcripts. 

Retracted: No

PubPeer comments:
 The Western blot panel of YY1 in Fig. 4 was partially reused in Fig. 6A. ![file] ,
Expression pattern of the thrombopoietin receptor (Mpl) in the murine central nervous system
Authors: Matthias Ballmaier
Anna Ivanova
Olaf Hoffmann
Christof Dame
Jens Wuerfel
Juan Zhang
Journal: BMC developmental biology (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Thrombopoietin; Mpl receptor; CNS; megakaryopoiesis; neurons
Affiliations: Department of Neonatology, Charité - Universitätsmedizin, Germany.

Abstract:  Background: Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons. Mpl expression has been analysed in brain tissue on transcript level and in cultured primary rat neurons and astrocytes on protein level. Herein, we analysed Mpl expression in the developing and adult murine CNS by immunohistochemistry and investigated the brain of mice with homozygous Mpl deficiency (Mpl-/-) by MRI. Results: Mpl was not detectable at developmental stages E12 to E15 in any resident cells of the CNS. From E18 onwards, robust Mpl expression was found in various brain areas, including cerebral cortex, olfactory bulb, thalamus, hypothalamus, medulla, pons, and the grey matter of spinal cord. However, major developmental changes became obvious: In the subventricular zone of the cerebral cortex Mpl expression occurred only during late gestation, while in the hippocampus Mpl expression was detectable for first time at stage P4. In the white matter of the cerebellum Mpl expression was restricted to the perinatal period. In the adult cerebellum, Mpl expression switched to Purkinje cell. The majority of other Mpl-positive cells were NeuN-positive neurons. None of the cells could be double-labelled with astrocyte marker GFAP. Mpl-/- mice showed no gross abnormalities of the brain. Conclusions: Our data locate Mpl expression to neurons at different subdivisions of the spinal cord, rhombencephalon, midbrain and prosencephalon. Besides neuronal cells Mpl protein is also expressed in Purkinje cells of the adult cerebellum. 

Retracted: No

PubPeer comments:
 image duplication, slightly repositioned ![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. ,
Dystrophic phenotype of canine X-linked muscular dystrophy is mitigated by adenovirus-mediated utrophin gene transfer
Authors: F Cozzi
R Gilbert
T Negri
F Andreetta
G Karpati
D Croci
M Cerletti
R Colpo
K E Davies
F Cornelio
O Pozza
M Mora
Journal: Gene Therapy (2003)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Utrophin; gene transfer; muscular dystrophy; dystrophin; Golden Retriever dogs

Abstract:  Utrophin is highly homologous and structurally similar to dystrophin, and in gene delivery experiments in mdx mice was able to functionally replace dystrophin. We performed mini-utrophin gene transfer in Golden Retriever dogs with canine muscular dystrophy (CXMD). Unlike the mouse model, the clinicopathological phenotype of CXMD is similar to that of Duchenne muscular dystrophy (DMD). We injected an adenoviral vector expressing a synthetic utrophin into tibialis anterior muscles of newborn dogs affected with CXMD and examined transgene expression by RNA and protein analysis at 10, 30 and 60 days postinjection in cyclosporin-treated and -untreated animals. Immunosuppression by cyclosporin was required to mitigate the immune response to viral and transgene antigens. RT-PCR analysis showed the presence of the exogenous transcript in the muscle of cyclosporin-treated and -untreated animals. The transgenic utrophin was efficiently expressed at the extrajunctional membrane in immunosuppressed dogs and this expression was stable for at least 60 days. We found reduced fibrosis and increased expression of dystrophin-associated proteins (DAPs) in association with muscle areas expressing the utrophin minigene, indicating that mini-utrophin can functionally compensate for lack of dystrophin in injected muscles. For this reason, utrophin transfer to dystrophin-deficient muscle appears as a promising therapeutic approach to DMD. 

Retracted: No

PubPeer comments:
 In that article, in section 5. Discussion and implications for research, the authors said:  However, the shift from class-based representations to those that have greater support for instances is not straightforward. Reflecting some of the limitations of class-based modelling discussed here, practitioners have recently begun to explore instance-based representations (Frisendal, 2016; Hills, 2016). Unfortunately, these efforts are largely occurring in isolation from decades of theoretical and empirical work on conceptual modelling and are currently not supported by academic research (pp. 15). In June 2000 in the ACM Transaction of Database Systems, a paper entitled  Emancipating instances from the tyranny of classes in information modeling proposed an instance-based modeling grammar . This article had a solid instance-based grammar. So how come this article wasn t even mentioned in the previous section in the paper? Both articles are from peer-reviewed journals. If the authors had put the above fact in their paper, it would have weakened seriously their case for reengineering conceptual modelling grammars for instances. ,
Modification of the early gene enhancer-promoter improves the oncolytic potency of adenovirus 11
Authors: Vipul Bhakta
Ming Yuan
Hexiao Wang
Pengju Wang
Guozhong Jiang
Yaohe Wang
Jiwei Wang
Rathi Gangeswaran
Nicholas R Lemoine
Heike Müller
Han Hsi Wong
Journal: Molecular Therapy (2012)
Discipline: CLINICAL MEDICINE
Keywords: Oncolytic adenoviruses; Ad5; Ad11; CD46 receptor; infectivity
Affiliations: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.

Abstract:  Oncolytic adenoviruses based on serotype 5 (Ad5) have several shortcomings, including the downregulation of its receptor in cancer cells, high prevalence of neutralizing antibodies and hepatotoxicity. Another adenoviral serotype, Ad11, could overcome these obstacles. Here, we show that human cancer cell lines express higher levels of the Ad11 receptor CD46, resulting in much better infectivity than Ad5. Surprisingly, only 36% (9/25) of the cell lines were more sensitive to Ad11- than to Ad5-mediated cytotoxicity. Investigations revealed that it was the transcription of Ad11 E1A, not CD46 expression or virus infectivity, which determined the cell's sensitivity to Ad11 killing. Ad11 E1A mRNA levels have an effect on viral DNA replication, structural protein synthesis and infectious particle production. To test the hypothesis that increased E1A transcription would lead to improved Ad11 replication in Ad5-sensitive (but Ad11-less sensitive) cells, two Ad11 mutants (Ad11-Ad5-P and Ad11-Ad5-EP) were constructed where either the E1A promoter or enhancer-promoter, respectively, was replaced by that of Ad5. Ad11-Ad5-EP demonstrated increased E1A mRNA levels and replication, together with enhanced oncolytic potency in vitro and in vivo. This effect was found in both the Ad5-sensitive and Ad11-sensitive cancer cells, broadening the range of tumors that could be effectively killed by Ad11-Ad5-EP. 

Retracted: No

PubPeer comments:
 This is a relatively recent paper, even more so when comment #1 was posted. Surely the authors have access to the primary data? , 
null, 
 #1 Figure 4d. Much more similar than expected. ![file] ,
OB-RGRP regulates the phosphorylation of JAK2 and STAT3 in primary rat adipocytes
Authors: Xiaolin Li
Guohui Wu
Xu Qin
Qi Zeng
Weihong Shi
Yungang Hu
Guanqun Wan
Journal: Artificial Cells Nanomedicine and Biotechnology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: JAK2; OB-RGRP; Obesity; STAT3; leptin
Affiliations: Department of Oral and Maxillofacial Surgery, Jiangxi Provincial People’s Hospital, Nanchang, China

Abstract:  This study aimed to explore the role of obestatin R gene-related protein (OB-RGRP) in autocrine signal transduction of adipocytes. Primary rat adipocytes were isolated and verified by microscopic observation and oil red O staining. OB-RGRP expression vector and OB-RGRP siRNA (si-OB-RGRP) were constructed and transfected into adipocytes. Adipocytes were then divided into five groups: (1) Control; (2) Vector (empty expression vector); (3) OB-RGRP (OB-RGRP expression vector); (4) si-OB-RGRP NC (si-OB-RGRP negative control); (5) si-OB-RGRP. mRNA and protein levels of OB-RGRP, JAK2, phosphorylated JAK2 (p-JAK2), STAT3 and phosphorylated STAT3 (p-STAT3) were examined using RT-PCR and western blot, respectively. Results showed that mRNA and protein levels of OB-RGRP in the Vector and si-OB-RGRP NC groups were similar to those in the Control group. Their levels in the si-OB-RGRP and OB-RGRP groups were significantly down-regulated and up-regulated (p &lt; .05), respectively, in comparison with the control cells. There was no significant difference in the mRNA and protein levels of JAK2 and STAT3 among various groups. Moreover, the si-OB-RGRP NC and Vector groups induced similar ratios of p-JAK2 to JAK2 (p-JAK2/JAK2) and p-STAT3 to STAT3 (p-STAT3/STAT3) to the Control group. However, these two ratios in the si-OB-RGRP and OB-RGRP groups were significantly reduced and elevated (p &lt; .05), respectively, in comparison with the Control group. These results suggested that OB-RGRP overexpression enhanced the levels of p-JAK2 and p-STAT3 while OB-RGRP silencing lowered their levels. In conclusion, OB-RGRP regulated the phosphorylation of JAK2 and STAT3 in primary rat adipocytes. 

Retracted: No

PubPeer comments:
 In Figure 1, a micrograph has been duplicated and presented as something else. ![file] ,
Adenosine A2a receptor-mediated, normoxic induction of HIF-1 through PKC and PI-3K-dependent pathways in macrophages
Authors: Emanuele Albano
Elisa Alchera
Gaetano Cairo
Massimo Locati
Lorenza Tacchini
Maria Paola Nitti
Cristina De Ponti
Rita Carini
Journal: Journal of leukocyte biology (2007)
Discipline: IMMUNOLOGY
Keywords: Adenosine; HIF-1; Macrophages; VEGF; A(2A) receptor
Affiliations: Istituto di Patologia Generale, Università di Milano, Italy.

Abstract:  Adenosine released by cells in injurious or hypoxic environments has tissue-protecting and anti-inflammatory effects, which are also a result of modulation of macrophage functions, such as vascular endothelial growth factor (VEGF) production. As VEGF is a well-known target of hypoxia-inducible factor 1 (HIF-1), we hypothesized that adenosine may activate HIF-1 directly. Our studies using subtype-specific adenosine receptor agonists and antagonists showed that by activating the A(2A) receptor, adenosine treatment induced HIF-1 DNA-binding activity, nuclear accumulation, and transactivation capacity in J774A.1 mouse macrophages. Increased HIF-1 levels were also found in adenosine-treated mouse peritoneal macrophages. The HIF-1 activation induced by the A(2A) receptor-specific agonist CGS21680 required the PI-3K and protein kinase C pathways but was not mediated by changes in iron levels. Investigation of the molecular basis of HIF-1 activation revealed the involvement of transcriptional and to a larger extent, translational mechanisms. HIF-1 induction triggered the expression of HIF-1 target genes involved in cell survival (aldolase, phosphoglycerate kinase) and VEGF but did not induce inflammation-related genes regulated by HIF-1, such as TNF-alpha or CXCR4. Our results show that the formation of adenosine and induction of HIF-1, two events which occur in response to hypoxia, are linked directly and suggest that HIF-1 activation through A(2A) receptors may contribute to the anti-inflammatory and tissue-protecting activity of adenosine. 

Retracted: No

PubPeer comments:
 ![file] , 
 #1 See also Fig 3D from [Gammella, Cairo Tacchini (2010)] . ![] , 
 Fig 3A *[below]*, compared with *[above]* 2B from [Tacchini et al (2008)] . ![file] , 
 Comparing Fig 1D *[left]* against *[right]* Fig 1A from [Spagnuolo et al (2011)] : ![file] Surprisingly similar after a horizontal flip. ,
Tat peptide as an efficient molecule to translocate gold nanoparticles into the cell nucleus
Authors: Catherine C Berry
Jesus M de la Fuente
Journal: Bioconjugate Chemistry (0)
Discipline: CHEMISTRY
Keywords: nanoparticles; nuclear targeting; synthesis; gold nanoparticles; Tat protein-derived peptide sequence
Affiliations: Centre for Cell Engineering, Institute of Biomedical and Life Science, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK. 

Abstract:  The labeling of targeting molecules with nanoparticles has revolutionized the visualization of cellular or tissue components by electron microscopy. A particularly desirable target is the nucleus, because the genetic information is there. To date, utilizing nanoparticles for nuclear targeting has not proved very successful due to the impermeable nature of the plasma and nuclear membranes; thus nanoparticle design and synthesis is a critical factor. We report in this article the synthesis of water-soluble gold nanoparticles functionalized with a Tat protein-derived peptide sequence by a straightforward and economical methodology. The particles were subsequently tested in vitro with a human fibroblast cell line by optical and transmission electron microscopy to determine the biocompatibility of these nanoparticles and whether the functionalization with the translocation peptide allowed particles to transfer across the cell membrane and locate in the nucleus. 

Retracted: No

PubPeer comments:
 Identified by another reader. Both papers: https: pubpeer.com publications BB625E026960B628B341FBB9ACE318 https: pubpeer.com publications 7F0C9D7095FB709B597250DAF82108 *** ![file] ,
Role of bone morphogenetic proteins in form-deprivation myopia sclera
Authors: Xian Yang
Lina Zhang
Guiqiu Zhao
Qing Wang
Shichao Xing
Journal: Molecular vision (2011)
Discipline: CLINICAL MEDICINE
Keywords: bone morphogenetic proteins; sclera remodeling; myopia induction; sclera fibroblasts; cell culture
Affiliations: Department of Ophthalmology, the Affiliated Hospital of Medical College, Qingdao University, Qingdao, China.

Abstract:  Purpose: To clarify the role of bone morphogenetic proteins (BMP-2,-4,-5) in sclera remodeling during myopia induction and their effect on sclera fibroblasts in cell culture. Methods: Reverse transcription and polymerase chain reaction (RT-PCR) as well as immunofluorescence were used to detect the expression of the BMPs in human and guinea pig posterior sclera. In guinea pig form-deprivation myopia (FDM) model, RT-PCR and western blotting were used to investigate changes of BMP expression in the posterior sclera. Human sclera fibroblast (HSF) was primarlly cultured and treated with various doses of BMP-2. Cell proliferation was evaluated by the MTT assay. RT-PCR and western-blot were used to determine the changes of collagen I, aggrecan, and possible activated signal pathway. Cell phenotype and activated signal pathway, especially for α-smooth muscle actin (α-SMA) and phospho-smad1/5/8 were then further investigated by cytoimmunofluorescence staining. Results: Both human and guinea pig sclera express BMP-2, -4, and -5. In FDM eyes, BMP-2 and BMP-5 expression were reduced in the posterior sclera. Cell proliferation increased significantly (p&lt;0.05) and more cells differentiated into myofibroblast when incubated with 100 ng/ml BMP-2 . The expressions of collangen I, aggrecan, and phospho-smad1/5/8 significantly increased (p&lt;0.05 respectively) as well. Conclusions: Various BMPs were expressed in human and guinea pig sclera. In the posterior sclera, the expressions of BMP-2 and BMP-5 decreased in FDM eyes. BMP-2 might be able to promote HSF proliferation and differentiation, as well as to help extracellular matrix synthesis potentially through classical Smad pathway. 

Retracted: No

PubPeer comments:
 image duplication ![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. ,
The function of bacterial HtrA is evolutionally conserved in mammalian HtrA2/Omi
Authors: Hea-Jong Chung
Mohammad Abu Hena Mostofa Jamal
Seong-Tshool Hong
Journal: Scientific Reports (2020)
Discipline: Multidisciplinary
Keywords: HtrA2/Omi; Parkinson's disease; α-Syn; neurodegeneration; mnd2 mice
Affiliations: Department of Biomedical Sciences and Institute for Medical Science, Chonbuk National University Medical School, Jeonju, Chonbuk, 54907, South Korea., Gwangju Center, Korea Basic Science Institute, Gwangju, South Korea., Department of Biotechnology and Genetic Engineering, Islamic University, Kushtia, 7003, Bangladesh., Department of Biomedical Sciences and Institute for Medical Science, Chonbuk National University Medical School, Jeonju, Chonbuk, 54907, South Korea. .

Abstract:  Although the malfunction of HtrA2/Omi leads to Parkinson's disease (PD), the underlying mechanism has remained unknown. Here, we showed that HtrA2/Omi specifically removed oligomeric α-Syn but not monomeric α-Syn to protect oligomeric α-Syn-induced neurodegeneration. Experiments using mnd2 mice indicated that HtrA2/Omi degraded oligomeric α-Syn specifically without affecting monomers. Transgenic Drosophila melanogaster experiments of the co-expression α-Syn and HtrA2/Omi and expression of genes individually also confirmed that pan-neuronal expression of HtrA2/Omi completely rescued Parkinsonism in the α-Syn-induced PD Drosophila model by specifically removing oligomeric α-Syn. HtrA2/Omi maintained the health and integrity of the brain and extended the life span of transgenic flies. Because HtrA2/Omi specifically degraded oligomeric α-Syn, co-expression of HtrA2/Omi and α-Syn in Drosophila eye maintained a healthy retina, while the expression of α-Syn induced retinal degeneration. This work showed that the bacterial function of HtrA to degrade toxic misfolded proteins is evolutionarily conserved in mammalian brains as HtrA2/Omi. 

Retracted: No

PubPeer comments:
 In fig3 a and b, most black pictures are not real pictures. They are just black boxes. (This becomes obvious by changing the brightness contrast) In Fig5a, control 40days, syn staining = hOmi syn 40days syn staining control 10days omi staining = control 40days omi staining In Fig5b, omi, 10days, syn staining = control, 40days, omi staining In Fig6b, control 10days = omi 10 days control 40 days = omi 40 days In Fig 6C-D, male, omi 10days = female, omi,syn, 10days male omi, syn 40days = female omi, 40days female control 10 days = female control 40 days , 
 ![file] In fig3 a and b, most black pictures are not real pictures. They are just black boxes. (This become obvious by changing the brightness contrast) In Fig5a, control 40days, syn staining = hOmi syn 40days syn staining control 10days omi staining = control 40days omi staining In Fig5b, omi, 10days, syn staining = control, 40days, omi staining In Fig6b, control 10days = omi 10 days control 40 days = omi 40 days In Fig 6C-D, male, omi 10days = female, omi,syn, 10days male omi, syn 40days = female omi, 40days female control 10 days = female control 40 days ,