PReD-Bench/PRed-Bench huggingface dataset:
CaMKII Negatively Regulates Calcineurin–NFAT Signaling in Cardiac Myocytes
Authors: Jutta Weisser-Thomas
Steven R Houser
Hajime Kubo
Marie Hanscome
Joan H Brown
Remus Berretta
Naser Jaleel
Scott M MacDonnell
Xiongwen Chen
Abdel-Karim Sabri
Jeffery D Molkentin
Qinghang Liu
Journal: Circulation Research (2009)
Discipline: CLINICAL MEDICINE
Keywords: Cardiac myocyte hypertrophy; intracellular Ca(2+); calmodulin; calcineurin; CaMKII
Affiliations: Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA., From the Department of Physiology (S.M.M., J.W.-T., H.K., M.H., N.J., R.B., X.C., A.-K.S., S.R.H.), Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pa; Cincinnati Children’s Hospital Medical Center (Q.L., J.D.M.), Ohio; and Department of Pharmacology (J.H.B.), University of California at San Diego, La Jolla.

Abstract:  Rationale: Pathological cardiac myocyte hypertrophy is thought to be induced by the persistent increases in intracellular Ca(2+) needed to maintain cardiac function when systolic wall stress is increased. Hypertrophic Ca(2+) binds to calmodulin (CaM) and activates the phosphatase calcineurin (Cn) and CaM kinase (CaMK)II. Cn dephosphorylates cytoplasmic NFAT (nuclear factor of activated T cells), inducing its translocation to the nucleus where it activates antiapoptotic and hypertrophic target genes. Cytoplasmic CaMKII regulates Ca(2+) handling proteins but whether or not it is directly involved in hypertrophic and survival signaling is not known. Objective: This study explored the hypothesis that cytoplasmic CaMKII reduces NFAT nuclear translocation by inhibiting the phosphatase activity of Cn. Methods and results: Green fluorescent protein-tagged NFATc3 was used to determine the cellular location of NFAT in cultured neonatal rat ventricular myocytes (NRVMs) and adult feline ventricular myocytes. Constitutively active (CaMKII-CA) or dominant negative (CaMKII-DN) mutants of cytoplasmic targeted CaMKII(deltac) were used to activate and inhibit cytoplasmic CaMKII activity. In NRVM CaMKII-DN (48.5+/-3%, P&lt;0.01 versus control) increased, whereas CaMKII-CA decreased (5.9+/-1%, P&lt;0.01 versus control) NFAT nuclear translocation (Control: 12.3+/-1%). Cn inhibitors were used to show that these effects were caused by modulation of Cn activity. Increasing Ca(2+) increased Cn-dependent NFAT translocation (to 71.7+/-7%, P&lt;0.01) and CaMKII-CA reduced this effect (to 17.6+/-4%). CaMKII-CA increased TUNEL and caspase-3 activity (P&lt;0.05). CaMKII directly phosphorylated Cn at Ser197 in CaMKII-CA infected NRVMs and in hypertrophied feline hearts. Conclusion: These data show that activation of cytoplasmic CaMKII inhibits NFAT nuclear translocation by phosphorylation and subsequent inhibition of Cn. 

Retracted: No

PubPeer comments:
 Much more similar than expected. https: imgur.com yPdtH5D ,
L3MBTL1, a histone-methylation-dependent chromatin lock
Authors: Robert J Sims 3rd
Guohong Li
Hediye Erdjument-Bromage
Piernicola Boccuni
Alejandro Vaquero
Danny Reinberg
Patrick Trojer
Yuh-Hwa Wang
Nagesh Kalakonda
Donghoon Lee
Paul Tempst
Stephen D Nimer
Journal: Cell (2007)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: histone lysine methylation; transcriptional repression; facultative heterochromatin; malignant-brain-tumor protein; L3MBTL1
Affiliations: Howard Hughes Medical Institute, University of Medicine and Dentistry of New Jersey, 683 Hoes Lane, Piscataway, NJ 08854, USA.

Abstract:  Distinct histone lysine methylation marks are involved in transcriptional repression linked to the formation and maintenance of facultative heterochromatin, although the underlying mechanisms remain unclear. We demonstrate that the malignant-brain-tumor (MBT) protein L3MBTL1 is in a complex with core histones, histone H1b, HP1gamma, and Rb. The MBT domain is structurally related to protein domains that directly bind methylated histone residues. Consistent with this, we found that the L3MBTL1 MBT domains compact nucleosomal arrays dependent on mono- and dimethylation of histone H4 lysine 20 and of histone H1b lysine 26. The MBT domains bind at least two nucleosomes simultaneously, linking repression of transcription to recognition of different histone marks by L3MBTL1. Consistently, L3MBTL1 was found to negatively regulate the expression of a subset of genes regulated by E2F, a factor that interacts with Rb. 

Retracted: No

PubPeer comments:
 Figure 1D appears the same as Figure 3 in Beck DB et al., Cold Spring Harbor Symposia on Quantitative Biology (2010), DOI: 10.1101 sqb.2010.75.052, https: pubpeer.com publications 02F2B991497ECA97B1E6AD40149BD9 I will therefore post the same image here as with the other paper, marked for possible duplicated areas. ![file] , 
 Figure 2B. * Some repetitive elements appear to be visible in one of the three panels. ![file] ,
The clinical outcomes of surgical treatment of noncontiguous spinal tuberculosis: a retrospective study in 23 cases
Authors: Kefeng Zeng
Jia Huang
Hongqi Zhang
Qile Gao
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: retrospective clinical study; noncontiguous spinal tuberculosis; surgical treatment; therapeutic strategies; posterior transforaminal debridement
Affiliations: From the Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, China.

Abstract:  Study design: A retrospective clinical study. Objective: To evaluate the clinical efficacy of the surgical treatment of noncontiguous spinal tuberculosis (NSTB), and to discuss its therapeutic strategies. Methods: We performed a retrospective review of clinical and radiographic data that were prospectively collected on 550 consecutive spinal tubercular patients including 27 patients who were diagnosed and treated as NSTB in our institution from June 2005 to June 2011. Apart from 4 patients being treated conservatively, the remainder received surgery by posterior transforaminal debridement, interbody fusion with instrumentation, posterior instrumentation and anterior debridement with fusion in a single or two-stage operation. The clinical outcomes were evaluated before and after treatment in terms of hematologic and radiographic examinations, bone fusion and neurologic status. The Oswestry Disability Index score was determined before treatment and at the last follow-up visit. Results: 23 patients (15 M/8F), averaged 44.6 ± 14.2 years old (range, 19 to 70 yd), who received surgical treatment, were followed up after surgery for a mean of 52.5 ± 19.5 months (range, 24 to 72 months). The kyphotic angle was changed significantly between pre- and postoperation (P&lt;0.05). The mean amount of correction was 12.6 ± 7.2 degrees, with a small loss of correction at last follow-up. All patients achieved solid bone fusion. No patients with neurological deficit deteriorated postoperatively. Neither mortalities nor any major complications were found. There was a significant difference of Oswestry Disability Index scores between preoperation and the final follow-up. Conclusion: The outcomes of follow-up showed that posterior and posterior-anterior surgical treatment methods were both viable surgical options for NSTB. Posterior transforaminal debridement, interbody fusion and posterior instrumentation, as a less invasive technique, was feasible and effective to treat specific tubercular foci. 

Retracted: Yes

PubPeer comments:
 See https: retractionwatch.com 2021 02 01 springer-nature-to-retract-chapter-on-sign-language-critics-call-unbelievably-insulting ,
Nanorods with multidimensional optical information beyond the diffraction limit
Authors: Gungun Lin
Shihui Wen
Jiajia Zhou
Bingyang Shi
Yongtao Liu
Fan Wang
Yung Doug Suh
Dayong Jin
Journal: Nature Communications (2020)
Discipline: Multidisciplinary
Keywords: nanostructures; heterogeneous; optical uniformity; diverse; nanorods
Affiliations: Institute for Biomedical Materials & Devices (IBMD), Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia., Centre for Motor Neuron Disease Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, 2109, Australia., Laboratory for Advanced Molecular Probing, Research Center for Bio Platform Technology, Korea Research Institute of Chemical Technology, Daejeon, 34114, South Korea., Institute for Biomedical Materials & Devices (IBMD), Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia. .

Abstract:  Precise design and fabrication of heterogeneous nanostructures will enable nanoscale devices to integrate multiple desirable functionalities. But due to the diffraction limit (~200 nm), the optical uniformity and diversity within the heterogeneous functional nanostructures are hardly controlled and characterized. Here, we report a set of heterogeneous nanorods; each optically active section has its unique nonlinear response to donut-shaped illumination, so that one can discern each section with super-resolution. To achieve this, we first realize an approach of highly controlled epitaxial growth and produce a range of heterogeneous structures. Each section along the nanorod structure displays tunable upconversion emissions, in four optical dimensions, including color, lifetime, excitation wavelength, and power dependency. Moreover, we demonstrate a 210 nm single nanorod as an extremely small polychromatic light source for the on-demand generation of RGB photonic emissions. This work benchmarks our ability toward the full control of sub-diffraction-limit optical diversities of single heterogeneous nanoparticles. 

Retracted: No

PubPeer comments:
 Supplementary Figure 8: * Parts of the cross-section profiles similar to each other, as highlighted by colored boxes. Maybe I am misunderstanding this figure, but are the noise parts of the plots expected to look so similar? ![file] , 
 There is nothing wrong with the data here. This figure is used to show how to resolve two active segments. We use one cross section profile and move it away step by step to illustrate how the two negative contrasts can be resolved in single nanorods through super resolution imaging. As descript in the figure caption, (c) is the corresponding cross-section profile in figure b (which is the data from the experiment with one PSF). (d-f) is the merged PSF with different central shift distance of 30 nm, 50 nm, and 70 nm respectively (which is the simulation data using the PSF data in figure c). We also have the related discussion after the figure: u201cu2026. distance from 30 to 70 nm has been simulated, where we overlap two experimental PSFu2026.u201d. ,
Role of heparan sulfate in mediating CXCL8-induced endothelial cell migration
Authors: Ye Zeng
Linshen Xie
Xiaoheng Liu
Zhiping Yan
Jingxia Liu
Journal: PeerJ (2016)
Discipline: Multidisciplinary
Keywords: CXCL8; Cell migration; HUVEC; Heparan sulfate; Rho GTPases.
Affiliations: Institute of Biomedical Engineering, School of Preclinical and Forensic Medicine, Sichuan University, China, West China School of Public Health, No. 4 West China Hospital, Sichuan University, China

Abstract:  CXCL8 (Interleukin-8, IL-8) plays an important role in angiogenesis and wound healing by prompting endothelial cell migration. It has been suggested that heparan sulfate (HS) could provide binding sites on endothelial cells to retain and activate highly diffusible cytokines and inflammatory chemokines. In the present study, we aimed to test the hypothesis that HS is essential for enhancement of endothelial cell migration by CXCL8, and to explore the underlying mechanism by detecting the changes in expression and activity of Rho GTPases and in the organization of actin cytoskeleton after enzymatic removal of HS on human umbilical vein endothelial cells (HUVECs) by using heparinase III. Our results revealed that the wound healing induced by CXCL8 was greatly attenuated by removal of HS. The CXCL8-upregulated Rho GTPases including Cdc42, Rac1, and RhoA, and CXCL8-increased Rac1/Rho activity were suppressed by removal of HS. The polymerization and polarization of actin cytoskeleton, and the increasing of stress fibers induced by CXCL8 were also abolished by heparinase III. Taken together, our results demonstrated an essential role of HS in mediating CXCL8-induced endothelial cell migration, and highlighted the biological importance of the interaction between CXCL8 and heparan sulfate in wound healing. 

Retracted: No

PubPeer comments:
 Figure 4A. * Pink boxes: The 4h and 12h panels of the HepIII CXCL8 samples appear to overlap. ![file] ,
Valproic acid extends Caenorhabditis elegans lifespan
Authors: Kerry Kornfeld
James J Collins
Stacie Hughes
Cheng Huang
Kimberley Evason
Journal: Aging Cell (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Aging; Caenorhabditis elegans; lifespan extension; valproic acid; age-related disease
Affiliations: Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Ave., Campus Box 8103, St. Louis, MO 63110, USA.

Abstract:  Aging is an important biological phenomenon and a major contributor to human disease and disability, but no drugs have been demonstrated to delay human aging. Caenorhabditis elegans is a valuable model for studies of animal aging, and the analysis of drugs that extend the lifespan of this animal can elucidate mechanisms of aging and might lead to treatments for age-related disease. By testing drugs that are Food and Drug Administration approved for human use, we discovered that the mood stabilizer and anticonvulsant valproic acid (VA) extended C. elegans lifespan. VA also delayed age-related declines of body movement, indicating that VA delays aging. Valproic acid is a small carboxylic acid that is the most frequently prescribed anticonvulsant drug in humans. A structure-activity analysis demonstrated that the related compound valpromide also extends lifespan. Valproic acid treatment may modulate the insulin/IGF-1 growth factor signaling pathway, because VA promoted dauer larvae formation and DAF-16 nuclear localization. To investigate the mechanism of action of VA in delaying aging, we analyzed the effects of combining VA with other compounds that extend the lifespan of C. elegans. Combined treatment of animals with VA and the heterocyclic anticonvulsant trimethadione caused a lifespan extension that was significantly greater than treatment with either of these drugs alone. These data suggest that the mechanism of action of VA is distinct from that of trimethadione, and demonstrate that lifespan-extending drugs can be combined to produce additive effects. 

Retracted: No

PubPeer comments:
 Lifespan extension by valproic acid could not be replicated by the Caenorhabditis Intervention Testing Program in N2. It actually shortened lifespan in other genetic backgrounds (Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects, 10.1038 ncomms14256) ,
Human ESC‐sEVs alleviate age‐related bone loss by rejuvenating senescent bone marrow‐derived mesenchymal stem cells
Authors: Liangzhi Gong
Juntao Zhang
Yang Wang
Yu Chen
Ji Yuan
Bi Chen
Qing Li
Guowen Hu
Zhifeng Deng
Yongjin Sun
Zongping Xie
Xin Niu
Journal: Journal of Extracellular Vesicles (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Extracellular vesicle; bone loss; bone marrow MSCs; cellular senescence; embryonic stem cells.
Affiliations: Institute of Microsurgery on ExtremitiesDepartment of Orthopedic SurgeryShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina, Department of NeurosurgeryShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina

Abstract:  Tissue-resident stem cell senescence leads to stem cell exhaustion, which is a major cause of physiological and pathological ageing. Stem cell-derived extracellular vesicles (SC-EVs) have been reported in preclinical studies to possess therapeutic potential for diverse diseases. However, whether SC-EVs can rejuvenate senescent tissue stem cells to prevent age-related disorders still remains unknown. Here, we show that chronic application of human embryonic stem cell-derived small extracellular vesicles (hESC-sEVs) rescues the function of senescent bone marrow mesenchymal stem cells (BM-MSCs) and prevents age-related bone loss in ageing mice. Transcriptome analysis revealed that hESC-sEVs treatment upregulated the expression of genes involved in antiaging, stem cell proliferation and osteogenic differentiation in BM-MSCs. Furthermore, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified 4122 proteins encapsulated in hESC-sEVs. Bioinformatics analysis predicted that the protein components in the hESCs-sEVs function in a synergistic way to induce the activation of several canonical signalling pathways, including Wnt, Sirtuin, AMPK, PTEN signalling, which results in the upregulation of antiaging genes in BM-MSCs and then the recovery of senescent BM-MSCs function. Collectively, our findings reveal the effect of hESC-sEVs in reversing BM-MSCs senescence and age-related osteogenic dysfunction, thereby preventing age-related bone loss. Because hESC-sEVs could alleviate senescence of tissue-resident stem cells, they might be promising therapeutic candidates for age-related diseases. 

Retracted: No

PubPeer comments:
 I wonder why in Figure 5A and 5G, 5H, there is no difference between control groups 2, 6, 12 months, and no difference between treatment group 6, 12 months . ![image] ,
Conditional knockout of fibronectin abrogates mouse mammary gland lobuloalveolar differentiation
Authors: Lynn Huang
Alexander Y Nikitin
Andrea Flesken-Nikitin
Bendicht U Pauli
Le Cheng
Keyi Liu
Journal: Developmental Biology (2010)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Fibronectin; mammary gland development; conditional knockout; branching morphogenesis; ductal outgrowth
Affiliations: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

Abstract:  Fibronectin (Fn) plays an important part in the branching morphogenesis of salivary gland, lung, and kidney. Here, we examine the effect of the conditional knockout of Fn in the mammary epithelium [Fn(MEp-/-)] on postnatal mammary gland development, using Cre-loxP-mediated gene knockout technology. Our data show that Fn deletion causes a moderate retardation in outgrowth and branching of the ductal tree in 5-week-old mice. These defects are partially compensated in virgin 16-week-old mice. However, mammary glands consisting of Fn-deficient epithelial cells fail to undergo normal lobuloalveolar differentiation during pregnancy. The severity of lobuloalveolar impairment ranged from lobular hypoplasia to aplasia in some cases and was associated with the amount of Fn protein recovered from these glands. Decreased rates of mammary epithelial cell proliferation accounted for delayed ductal outgrowth in virgin and lack of alveologenesis in pregnant Fn(MEp-/-) mice. Concomitant decreased expression of integrin beta(1) (Itgb1) and lack of autophosphorylation of focal adhesion kinase (Fak) suggest that this pathology might, at least in part, be mediated by disruption of the Fn/Itgb1/Fak signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 10. Much more similar and different than expected. ![file] ,
Silencing of TGF-beta signalling by the pseudoreceptor BAMBI
Authors: H Delius
D Onichtchouk
Y G Chen
J Massagué
R Dosch
C Niehrs
V Gawantka
Journal: Nature (1999)
Discipline: Multidisciplinary
Keywords: Transforming growth factor-beta; TGF-beta; bone morphogenetic proteins; BMPs; activins
Affiliations: Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

Abstract:  Members of the transforming growth factor-beta (TGF-beta) superfamily, including TGF-beta, bone morphogenetic proteins (BMPs), activins and nodals, are vital for regulating growth and differentiation. These growth factors transduce their signals through pairs of transmembrane type I and type II receptor kinases. Here, we have cloned a transmembrane protein, BAMBI, which is related to TGF-beta-family type I receptors but lacks an intracellular kinase domain. We show that BAMBI is co-expressed with the ventralizing morphogen BMP4 (refs 5, 6) during Xenopus embryogenesis and that it requires BMP signalling for its expression. The protein stably associates with TGF-beta-family receptors and inhibits BMP and activin as well as TGF-beta signalling. Finally, we provide evidence that BAMBI's inhibitory effects are mediated by its intracellular domain, which resembles the homodimerization interface of a type I receptor and prevents the formation of receptor complexes. The results indicate that BAMBI negatively regulates TGF-beta-family signalling by a regulatory mechanism involving the interaction of signalling receptors with a pseudoreceptor. 

Retracted: No

PubPeer comments:
 Figure 4a. https: imgur.com j9SFgSy , 
 We note that the shown lanes with the arrows were indeed from separate gels and immunoblots that were spliced together later. The reason was that there were too many samples in that experiment to be loaded on one single gel, so they had to be split. Importantly though, all samples were from the very same experiment and are comparable. Nevertheless, we should have indicated this merging clearly and apologize for this omission. The omission does not affect the conclusion nor any statement of the publication. Ye-Guang Chen Tsinghua University Christof Niehrs German Cancer Research Center ,
An investigation of European pathologists' approach to diagnose microscopic colitis
Authors: Anne-Marie Kanstrup Fiehn
Peter Johan Heiberg Engel
Stefania Landolfi
Vincenzo Villanacci
Danny Goudkade
Lars Kristian Munck
Journal: Annals of diagnostic pathology (2020)
Discipline: CLINICAL MEDICINE
Keywords: Diagnostic approach; Inter-observer variation; Microscopic colitis; Pathology; Validation.
Affiliations: Department of Pathology, Zuyderland Medical Centre, Dr. H. van der Hoffplein 1, 6162 BG Geleen, the Netherlands. Electronic address: ., Department of Pathology, University Hospital of Copenhagen, Rigshospitalet, Frederik V's Vej 11, 2100 Copenhagen, Denmark., Department of Pathology, Hospital Universitaru Vall d'Hebron, CIBERONC, Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain., Department of Pathology, ASST Spedali Civili of Brescia, Piazzale Spedali Civili 1, 25123 Brescia BS, Italy., Department of Medical Gastroenterology, Zealand University Hospital Koege, 4600 Koege, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark., Department of Pathology, Zealand University Hospital Roskilde, Sygehusvej 9, 4000 Roskilde, Denmark.

Abstract:  Microscopic colitis (MC) comprising lymphocytic colitis (LC), collagenous colitis (CC) and the incomplete forms of microscopic colitis (MCi) are frequent causes of chronic watery diarrhea. The diagnosis is based on specific histological features in colonic biopsies. Especially regarding MCi, the histological features may be subtle. The PRO-MC collaboration was established in 2016 with the aims to systematically describe the disease course and to validate the diagnostic criteria of MC. In the present study, we analysed pathologists' initial approach to diagnose MC. Five pathologists with expertise in gastro-intestinal pathology reviewed the first 10 cases enrolled in the PRO-MC registry in six of the participating centres. Despite considerable differences in strategies in biopsy sampling, in choice of stains and in minimum number of biopsies and segments required for diagnosing MC, inter-observer agreement between the participating centres and expert pathologists as well as among the latter was substantial. Disagreed cases most often related to difficulties in distinguishing between MC subgroups. We recommend that pathologists as well as clinicians reach consensus in their diagnostic approach to MC, which is a prerequisite to compare MC cohorts internationally and to facilitate clinical MC trials and follow-up studies. 

Retracted: No

PubPeer comments:
 ![file] ![file] ![file] ,
Long noncoding RNA XIST enhances cerebral ischemia-reperfusion injury by regulating miR-486-5p and GAB2
Authors: H-Y Zhang
Y Wang
Y-B Liu
R Liu
W-P Wei
F Xiong
Journal: European review for medical and pharmacological sciences (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: LncRNA XIST; miR-486-5p; GAB2; cerebral I/R injury; oxygen-glucose deprivation reperfusion
Affiliations: Department of Neurosurgery, People's Hospital of Rizhao, Rizhao, Shandong, China. .

Abstract:  Objective: LncRNA XIST has been reported to act as diverse function in different human diseases. Our study is designed to detect the role of lncRNA XIST and the regulatory mechanisms of XIST/miR-486-5p/GAB2 in cerebral I/R injury. Materials and methods: In our article, SH-SY5Y cells were treated with oxygen-glucose deprivation reperfusion (OGDR) to mimic I/R injury. RT-qPCR assay was performed to detect the mRNA expression of XIST, GAB2 and miR-486-5p. The correlation between XIST and miR-486-5p, miR-486-5p and GAB2 were verified by RT-qPCR assay and Dual-Luciferase reporter assay. MTT assay was used to detect cell viability of SH-SY5Y cells treated with I/R. The protein expression of GAB2, apoptosis-related proteins (Bax/Bcl-2) were explored by Western blot assay. Results: XIST and GAB2 were significantly highly expressed, while miR-486-5p was low expressed in SH-SY5Y cells under I/R. XIST exacerbated the oxidative damage of I/R cells. Moreover, XIST was found to restrain cell viability and induce cell apoptosis. For our experiment, miR-486-5p was a target of XIST, and GAB2 was a downstream gene of miR-486-5p. Furthermore, miR-486-5p mimic promoted cell proliferation and inhibited cell apoptosis, while XIST co-transfection reversed the effect of miR-486-5p. In addition, XIST was found to impair the inhibitory effect of miR-486-5p on expression of GAB2 in I/R cells. Conclusions: Our results indicated that XIST promoted cerebral I/R injury via modulating miR-486-5p and GAB2. 

Retracted: No

PubPeer comments:
 ![file] The title, Introduction and Conclusions of this paper give the strong impression that cerebral ischaemia-reperfusion injuries were inflicted and aggravated. This was not the case. Neuroblasts (SH-SY5Y cell-line) were cultured for several hours with less-than-optimal oxygen and glucose, then restored to normal culture medium.  LncRNAs have been shown to play a *curial* part in cerebral I R injury.  Our results implied that XIST might be a *curial* regulator in cerebral I R injury . This aspect of the Vatican administration was new to me. ,
Nuclear factor-erythroid 2-related factor 3 (NRF3) is low expressed in colorectal cancer and its down-regulation promotes colorectal cancer malignance through activating EGFR and p38/MAPK
Authors: Shan Zhou
Zhenlin Zhang
Yuejin Li
Lei Wang
Jinping Lu
Chan Chen
Faqing Tang
Zigang Dong
Weiwei Wang
Journal: American journal of cancer research (2019)
Discipline: CLINICAL MEDICINE
Keywords: EGFR; NRF3; colorectal cancer; p38; tumorigenesis.
Affiliations: Department of Clinical Laboratory, Zhuhai Hospital, Jinan University Zhuhai 519000, Guangdong, China., Department of Clinical Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University Changsha 410013, China., Department of Clinical Laboratory, Changsha Central Hospital Changsha 410013, China., Hormel Institute, University of Minnesota 801 16th Avenue NE, Austin, MN 55912, USA.

Abstract:  Nuclear factor-erythroid 2-related factor 3 (NRF3), a nuclear transcription factor, has been implicated in various cellular processes including carcinogenesis. However, mechanisms underlying its regulation in carcinogenesis are unclear. Herein, we found that NRF3 is lowly expressed in colorectal cancer (CRC) tissues and cells, and NRF3 low-expressions in CRC tissue samples are associated with CRC carcinogenesis and poor patient outcomes. Nrf3-knockdown increased CRC cell growth, colony formation, and cell motility and invasion, and Nrf3-knockin dramatically decreased CRC cell growth and colony formation. Mechanistically, NRF3 increased CRC cell apoptosis and arrested cell G2/M stage. NRF3 was found to be reversely with epidermal growth factor receptor (EGFR) and p38. Strikingly, Nrf3-knockin dramatically decreased phosphorylated-EGFR at Tyrosine845 (pEGFR Tyr845) and phosphorylated-p38 at Threonine180/Tyrosine182 (p-p38 Thr180/Tyr182) expressions, and Nrf3-knockdown increased pEGFR Tyr845 and p-p38 Thr180/Tyr182. Moreover, NRF3 regulated EGFR and p38 down-stream molecules, protein kinase B (AKT), activating transcription factor (ATF) 2, and C/EBP homologous protein (CHOP) expressions. NRF3 loss-increased CRC growth through EGFR and p38 was confirmed in nude mice. Collectively, NRF3-loss in CRC cell increases EGFR and p38 phosphorylation activation, enhances cell proliferation and decreases cell apoptosis, and finally promotes CRC malignance. 

Retracted: No

PubPeer comments:
 BJP has chosen to correct irregularities in this articles: https: bpspubs.onlinelibrary.wiley.com doi 10.1111 bph.15296 These were the original images: Control and DMSO were at 0 and at 24 h the same sample: ![file] Figure 5a is a smaller section of Figure 2f. The label for treatment conditions was however different ![file] ,
Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans lifespan
Authors: Elizabeth A Schroeder
Katja Hebestreit
Carlos G Silva-García
Shuo Han
Anne Brunet
William B Mair
Journal: Nature (2017)
Discipline: Multidisciplinary
Keywords: Chromatin; metabolic states; lifespan regulation; COMPASS chromatin complex; H3K4me3
Affiliations: Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA., Genetics Graduate Program, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA., Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA., Glenn Laboratories for the Biology of Aging, Stanford University, Stanford, California 94305, USA.

Abstract:  Chromatin and metabolic states both influence lifespan, but how they interact in lifespan regulation is largely unknown. The COMPASS chromatin complex, which trimethylates lysine 4 on histone H3 (H3K4me3), regulates lifespan in Caenorhabditis elegans. However, the mechanism by which H3K4me3 modifiers affect longevity, and whether this mechanism involves metabolic changes, remain unclear. Here we show that a deficiency in H3K4me3 methyltransferase, which extends lifespan, promotes fat accumulation in worms with a specific enrichment of mono-unsaturated fatty acids (MUFAs). This fat metabolism switch in H3K4me3 methyltransferase-deficient worms is mediated at least in part by the downregulation of germline targets, including S6 kinase, and by the activation of an intestinal transcriptional network that upregulates delta-9 fatty acid desaturases. Notably, the accumulation of MUFAs is necessary for the lifespan extension of H3K4me3 methyltransferase-deficient worms, and dietary MUFAs are sufficient to extend lifespan. Given the conservation of lipid metabolism, dietary or endogenous MUFAs could extend lifespan and healthspan in other species, including mammals. 

Retracted: No

PubPeer comments:
 Readers should become aware of a recent preprint that calls into question part of the conclusions of the study by Han et al., 2017 entitled Loss of SET1 COMPASS methyltransferase activity reduces lifespan and fertility in Caenorhabditis elegans . https: www.biorxiv.org content 10.1101 2021.06.07.447374v1.full.pdf From the text: An earlier study reported that the lifespan of set-2(ok952) mutant animals was approximately 20% longer than that of wild-type animals (34), which contrasts with the observations in the present study. We were also unable to recapitulate the increase in lipid storage previously implicated in the lifespan extension of set-2(ok952) animals (35). ,
Histone deacetylase 6–mediated selective autophagy regulates COPD-associated cilia dysfunction
Authors: John Quackenbush
Hong Pyo Kim
Shyam S Biswal
Abhiram R Bhashyam
Kathleen J Haley
George R Washko
Hilaire C Lam
Hongwei Yao
Caroline A Owen
J Fah Sathirapongsasuti
Bin Shan
Stefan W Ryter
Chang Hyeok An
Augustine M K Choi
Anna L Chung
Morgan Cervo
Ashfaq Mahmood
Anju Singh
Irfan Rahman
Edwin K Silverman
Kenji Mizumura
Jonathan M Franks
Jeffery A Haspel
Suzanne M Cloonan
Yohannes Tesfaigzi
Journal: Journal of Clinical Investigation (2013)
Discipline: CLINICAL MEDICINE
Keywords: Chronic obstructive pulmonary disease (COPD); cigarette smoke (CS); airway inflammatory responses; epithelial cell dysfunction; cilia shortening

Abstract:  Chronic obstructive pulmonary disease (COPD) involves aberrant airway inflammatory responses to cigarette smoke (CS) that are associated with epithelial cell dysfunction, cilia shortening, and mucociliary clearance disruption. Exposure to CS reduced cilia length and induced autophagy in vivo and in differentiated mouse tracheal epithelial cells (MTECs). Autophagy-impaired (Becn1+/- or Map1lc3B-/-) mice and MTECs resisted CS-induced cilia shortening. Furthermore, CS increased the autophagic turnover of ciliary proteins, indicating that autophagy may regulate cilia homeostasis. We identified cytosolic deacetylase HDAC6 as a critical regulator of autophagy-mediated cilia shortening during CS exposure. Mice bearing an X chromosome deletion of Hdac6 (Hdac6-/Y) and MTECs from these mice had reduced autophagy and were protected from CS-induced cilia shortening. Autophagy-impaired Becn1-/-, Map1lc3B-/-, and Hdac6-/Y mice or mice injected with an HDAC6 inhibitor were protected from CS-induced mucociliary clearance (MCC) disruption. MCC was preserved in mice given the chemical chaperone 4-phenylbutyric acid, but was disrupted in mice lacking the transcription factor NRF2, suggesting that oxidative stress and altered proteostasis contribute to the disruption of MCC. Analysis of human COPD specimens revealed epigenetic deregulation of HDAC6 by hypomethylation and increased protein expression in the airways. We conclude that an autophagy-dependent pathway regulates cilia length during CS exposure and has potential as a therapeutic target for COPD. 

Retracted: No

PubPeer comments:
 Figure 9B. Much more similar than expected. https: imgur.com KC4wRrk , 
 2020 correction. https: www.jci.org articles view 143863 During the preparation of this manuscript, two panels of Figure 9B were inadvertently duplicated, resulting in an incorrect image for the ES group. ,
Distinguishing body lice from head lice by multiplex real-time PCR analysis of the Phum_PHUM540560 gene
Authors: Didier Raoult
Jean Marc Rolain
Rezak Drali
Philippe Brouqui
Amina Boutellis
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Body louse; head louse; genetic marker; multiplex real-time PCR; differentiation
Affiliations: Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France.

Abstract:  Background: Body louse or head louse? Once removed from their environment, body and head lice are indistinguishable. Neither the morphological criteria used since the mid-18th century nor the various genetic studies conducted since the advent of molecular biology tools have allowed body lice and head lice to be differentiated. In this work, using a portion of the Phum_PHUM540560 gene from the body louse, we aimed to develop a multiplex real-time polymerase chain reaction (PCR) assay to differentiate between body and head lice in a single reaction. Materials and methods: A total of 142 human lice were collected from mono-infested hosts from 13 countries on five continents. We first identified the louse clade using a cytochrome b (CYTB) PCR sequence alignment. We then aligned a fragment of the Phum_PHUM540560 gene amplified from head and body lice to design-specific TaqMan(©) FAM- and VIC-labeled probes. Results: All the analyzed lice were Clade A lice. A total of 22 polymorphisms between the body and head lice were characterized. The multiplex real-time PCR analysis enabled the body and head lice to be distinguished in two hours. This method is simple, with 100% specificity and sensitivity. Conclusions: We confirmed that the Phum_PHUM540560 gene is a useful genetic marker for the study of lice. 

Retracted: No

PubPeer comments:
 In Fig 4b, it seems that the same plot appeared twice, though the numbers on them were different. Any explanation from the authors? ![file] ,
Multifunctional role of Bcl-2 in malignant transformation and tumorigenesis of Cr(VI)-transformed lung cells
Authors: John B Barnett
Lan Guo
Mary E Davis
Liying Wang
Neelam Azad
Sudjit Luanpitpong
Djordje Medan
Bing-Hua Jiang
Yon Rojanasakul
Journal: PloS one (2012)
Discipline: Multidisciplinary
Keywords: B-cell lymphoma-2; apoptosis regulation; malignant transformation; tumorigenesis; hexavalent chromium
Affiliations: Department of Pharmaceutical Sciences, West Virginia University, Morgantown, West Virginia, United States of America.

Abstract:  B-cell lymphoma-2 (Bcl-2) is an antiapoptotic protein known to be important in the regulation of apoptosis in various cell types. However, its role in malignant transformation and tumorigenesis of human lung cells is not well understood. We previously reported that chronic exposure of human lung epithelial cells to the carcinogenic hexavalent chromium Cr(VI) caused malignant transformation and Bcl-2 upregulation; however, the role of Bcl-2 in the transformation is unclear. Using a gene silencing approach, we showed that Bcl-2 plays an important role in the malignant properties of Cr(VI)-transformed cells. Downregulation of Bcl-2 inhibited the invasive and proliferative properties of the cells as well as their colony forming and angiogenic activities, which are upregulated in the transformed cells as compared to control cells. Furthermore, animal studies showed the inhibitory effect of Bcl-2 knockdown on the tumorigenesis of Cr(VI)-transformed cells. The role of Bcl-2 in malignant transformation and tumorigenesis was confirmed by gene silencing experiments using human lung carcinoma NCI-H460 cells. These cells exhibited aggressive malignant phenotypes similar to those of Cr(VI)-transformed cells. Knockdown of Bcl-2 in the H460 cells inhibited malignant and tumorigenic properties of the cells, indicating the general role of Bcl-2 in human lung tumorigenesis. Ingenuity Pathways Analysis (IPA) revealed potential effectors of Bcl-2 in tumorigenesis regulation. Additionally, using IPA together with ectopic expression of p53, we show p53 as an upstream regulator of Bcl-2 in Cr(VI)-transformed cells. Together, our results indicate the novel and multifunctional role of Bcl-2 in malignant transformation and tumorigenesis of human lung epithelial cells chronically exposed to Cr(VI). 

Retracted: No

PubPeer comments:
 Figure 3E appears to have a repeated image. *** ![file] ,
Histatin‐1 is an endogenous ligand of the sigma‐2 receptor
Authors: Kyung-No Son
Dhara Shah
Deepak Shukla
Arun Balasubramaniam
Hyunjoon Kong
Stephanie M Cologna
Sushma Kalmodia
Vinay Kumar Aakalu
Ryan Cree Miller
Marwan Ali
Hyun Lee
Journal: FEBS Journal (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: MAC30; TMEM97; antimicrobial peptide; histatin-1; migration
Affiliations: Department of Ophthalmology and Visual Sciences University of Illinois at Chicago  USA, Department of Pharmaceutical Science and Biophysics Core at Research Resources Center University of Illinois at Chicago  USA, Department of Chemical &amp; Biomolecular Engineering University of Illinois at Urbana‐Champaign  USA, Department of Chemistry University of Illinois at Chicago  USA

Abstract:  The Sigma-2 receptor (S2R) (a.k.a TMEM97) is an important endoplasmic reticular protein involved in cancer, cholesterol processing, cell migration, and neurodegenerative diseases, including Niemann-Pick Type C. While several S2R pharmacologic agents have been discovered, its recent (2017) cloning has limited biological investigation, and no endogenous ligands of the S2R are known. Histatins are a family of endogenous antimicrobial peptides that have numerous important effects in multiple biological systems, including antifungal, antibacterial, cancer pathogenesis, immunomodulation, and wound healing. Histatin-1 (Hst1) has important roles in epithelial wound healing and cell migration, and is the primary wound healing agent in saliva. Little is understood about the downstream machinery that underpins the effects of histatins, and no mammalian receptor is known to date. In this study, we show, using biophysical methods and functional assays, that Hst1 is an endogenous ligand for S2R and that S2R is a mammalian receptor for Hst1. 

Retracted: No

PubPeer comments:
  **Acknowledgments** We acknowledge and appreciate our colleagues for their valuable suggestions and technical assistance for this study. This specific acknowledgement sentence often appears in the products of papermills. [Dimensions.ai] helpfully provides a graph of its popularity against time. ![file] ------------------------------------------------ Figs 2E, 4D, 6C. ![file] Figs 1I K, 2B, 3D E G I, 4B, 7B, 5B. ![file] A surprising number of papers have WBs that sample the same corner of  morphology space , resembling rows of bow-ties on a grainy background. Here, Figs 2E, 3C G I, 4B F, 5A B C H, 6C from [Lin et al (2021)] . ![file] Figs 1D H K, 2F I, 3D H from [Qi et al (2021)] . ![file] Figs 3B D E G K, 4B D F H, 5A G C from [Zhou et al (2020)] . ![file] ,
Phosphorylation of cGAS by CDK1 impairs self-DNA sensing in mitosis
Authors: Li Zhong
Qiang Chen
Ming-Ming Hu
Ying Liu
Li-Jun Bian
Hong-Bing Shu
Journal: Cell Discovery (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cell division; Innate immunity.
Affiliations: Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism Medical Research Institute, Wuhan University, Wuhan, 430071 China.

Abstract:  The cyclic GMP-AMP synthase (cGAS) is a widely used DNA sensor, which detects cytosolic DNA species without a preference of self or non-self microbial DNA in interphase to initiate innate immune response. How cGAS is regulated to avoid self-DNA sensing upon nuclear envelope breakdown (NEBD) during mitosis remains enigmatic. Here we show that cGAS is mostly localized in the cytoplasm in interphase and rapidly translocated to chromosomes upon NEBD in mitosis. The major mitotic kinase CDK1-cyclin B complex phosphorylates human cGAS at S305 or mouse cGAS at S291, which inhibits its ability to synthesize cGAMP upon mitotic entry. The type 1 phosphatase PP1 dephosphorylates cGAS upon mitotic exit to enable its DNA sensing ability. Our findings reveal a mechanism on how the DNA sensor cGAS is post-translationally regulated by cell cycle-dependent enzymes to ensure its proper activation for host defense of cytosolic DNA in interphase and inert to self-DNA in mitosis. 

Retracted: No

PubPeer comments:
 ![file] ,
RVG29-modified microRNA-loaded nanoparticles improve ischemic brain injury by nasal delivery
Authors: Lihua Yang
Bixi Sun
Rubin Hao
Chun Ma
Shuling Li
Journal: Drug Delivery (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Ischemic brain injury; Nose-to-brain; RVG29; miRNA.
Affiliations: Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, ChangChun, Jilin, China;, School of Pharmaceutical Sciences, Jilin University, ChangChun, Jilin, China;, Affiliated Hospital of Changchun University of Chinese medicine, ChangChun, Jilin, China

Abstract:  Effective nose-to-brain delivery needs to be developed to treat neurodegenerative diseases. Regulating miR-124 can effectively improve the symptoms of ischemic brain injury and provide a certain protective effect from brain damage after cerebral ischemia. We used rat models of middle cerebral artery occlusion (t-MCAO) with ischemic brain injury, and we delivered RVG29-NPs-miR124 intranasally to treat neurological damage after cerebral ischemia. Rhoa and neurological scores in rats treated by intranasal administration of RVG29-PEG-PLGA/miRNA-124 were significantly lower than those in PEG-PLGA/miRNA-124 nasal administration and RVG29-PLGA/miRNA-124 nasal administration group treated rats. These results indicate that the nose-to-brain delivery of PLGA/miRNA-124 conjugated with PEG and RVG29 alleviated the symptoms of cerebral ischemia-reperfusion injury. Thus, nasal delivery of RVG29-PEG-PLGA/miRNA-124 could be a new method for treating neurodegenerative diseases. 

Retracted: No

PubPeer comments:
 Fig 4. A and B look like the same, except that the 1st row of A has a strange separation. Also, green boxed DAPI and Merge may be swapped. ![file] ,
AMPK activation increases postoperative cognitive impairment in intermittent hypoxia rats via direct activating PAK2
Authors: Wenxiang Qing
Xi Mei
Guolin Tan
Journal: Behavioural Brain Research (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: AMPK; Neuroinflammation; Obstructive sleep apnea-hypopnea syndrome; PAK2; Postoperative cognitive impairment.
Affiliations: Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, China., Department of Otolaryngology, Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, China. Electronic address: .

Abstract:  The pathogenesis of postoperative cognitive impairment of obstructive sleep apnea-hypopnea syndrome (OSAHS) individuals remains unclear. AMP activated protein kinase (AMPK) is a ubiquitous sensor/effector of cell stresses. Thus we detected the role and underlying mechanisms of AMPK in postoperative cognitive impairment of OSAHS individuals in intermittent hypoxia rats. Cognitive function was evaluated by novel object recognition test and Barnes maze during the first 4 days after laparotomy. We found that laparotomy induced postoperative cognitive impairment and AMPK activation in intermittent hypoxia rats, but not in adult rats. Inhibiting AMPK activation via Compound C during laparotomy improved postoperative cognitive impairment and alleviated surgery-induced upregulation of p-PAK2, AMPK-PAK2 complex, and neuroinflammation (marked by microglial activation and IL-1β level) in intermittent hypoxia rats. These data suggested that AMPK played an important role in postoperative cognitive impairment of OSAHS individuals via directly activating PAK2. 

Retracted: No

PubPeer comments:
 The two marked bands from Figure 3E appear unexpectedly similar. *** Figure 3E and Figure 3 caption. ![file] ,