PReD-Bench/PRed-Bench huggingface dataset:
The combination of db-cAMP and ChABC with poly(propylene carbonate) microfibers promote axonal regenerative sprouting and functional recovery after spinal cord hemisection injury
Authors: Tongliang Xia
Anjing Chen
Bin Huang
Shugan Zhu
Shaowei Zhu
Benlin Wang
Jiangang Wang
Jian Wang
Gang Li
Lei Gao
Shilei Ni
Xingang Li
Journal: Biomedicine & Pharmacotherapy (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ChABC; Electrospinning; PPC; SCI; db-cAMP.
Affiliations: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107# Wenhua Xi Road, Jinan, 250012, PR China., Jiyang County People's Hospital of Shandong Provence, 9# Xinyuan Street, Jinyang County, Jinan, 251400, PR China., Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107# Wenhua Xi Road, Jinan, 250012, PR China; Department of Biomedicine, University of Bergen, Jonas Lies Vei 91, 5009 Bergen, Norway., Department of Neurology, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, PR China., Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, 107# Wenhua Xi Road, Jinan, 250012, PR China. Electronic address: .

Abstract:  This study describes the use of poly(propylene carbonate) (PPC) electrospun microfibres impregnated with a combination of dibutyryl cyclic adenosine monophosphate (db-cAMP) and chondroitinase ABC (ChABC) in the treatment of right-side hemisected spinal cord injury (SCI). Release of db-cAMP and/or ChABC from the microfibres was assessed in vitro using high-performance liquid chromatography (HPLC). Drug-impregnated microfibres were implanted into the hemisected thoracic spinal cord of rats, and treatment was evaluated using functional recovery examinations and immunohistochemistry. Our results demonstrated that the microfibres containing db-cAMP and/or ChABC displayed a stable and prolonged release of each agent. Sustained delivery of db-cAMP and/or ChABC was found to promote axonal regenerative sprouting, functional recovery, and reduced glial scar formation when compared to untreated control animals. The combination of both db-cAMP and ChABC was determined to be more effective than using either drug alone in the treatment of SCI. These findings demonstrate the feasibility of using PPC electrospun microfibres for multi-drug combination therapy in SCI. 

Retracted: No

PubPeer comments:
 In Table 2 and 4, there are many repetitive numbers. ![file] ,
SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression
Authors: X Jing
S Goel
S K Pandey
S M Dhanasekaran
R Tiwari
S Shukla
V Bhatia
B Ateeq
Journal: Oncogenesis (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Colorectal cancer; SPINK1; therapeutic targets; KRAS; BRAF
Affiliations: Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India., Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA., 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA [2] Department of Pathology, University of Michigan, Ann Arbor, MI, USA.

Abstract:  Colorectal cancer (CRC) is the third most common cancer in the world, and second leading cause of cancer deaths in the US. Although, anti-EGFR therapy is commonly prescribed for CRC, patients harboring mutations in KRAS or BRAF show poor treatment response, indicating an ardent demand for new therapeutic targets discovery. SPINK1 (serine peptidase inhibitor, Kazal type 1) overexpression has been identified in many cancers including the colon, lung, breast and prostate. Our study demonstrates the functional significance of SPINK1 in CRC progression and metastases. Stable knockdown of SPINK1 significantly decreases cell proliferation, invasion and soft agar colony formation in the colon adenocarcinoma WiDr cells. Conversely, an increase in these oncogenic phenotypes was observed on stimulation with SPINK1-enriched conditioned media (CM) in multiple benign models such as murine colonic epithelial cell lines, MSIE and YAMC (SPINK3-negative). Mechanistically, SPINK1 promotes tumorigenic phenotype by activating phosphatidylinositol 3-kinase (PI3K/AKT) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways, and the SPINK1-positive WiDr cells are sensitive to AKT and MEK inhibitors. Importantly, SPINK1 silencing mediated upregulation of various Metallothionein isoforms, considered as tumor suppressors in CRC, confer sensitivity to doxorubicin, which strengthens the rationale for using the combinatorial treatment approach for the SPINK1-positive CRC patients. Furthermore, in vivo studies using chicken chorioallantoic membrane assay, murine xenograft studies and metastasis models further suggest a pivotal role of SPINK1 in CRC progression and metastasis. Taken together, our study demonstrates an important role for the overexpressed SPINK1 in CRC disease progression, a phenomenon that needs careful evaluation towards effective therapeutic target development. 

Retracted: No

PubPeer comments:
 Two images in Figure 3f and 3g appear to overlap, partly marked in red. *** ![file] *** ![file] ,
Why I’m not applying for promotion
Authors: Phil Cassey
Journal: Nature (2019)
Discipline: Multidisciplinary
Keywords: Careers; Ecology; Lab life.

Abstract: Phill Cassey outlines one proactive step to support diversity in his workplace. Phill Cassey outlines one proactive step to support diversity in his workplace.

Retracted: No

PubPeer comments:
 The argument put forward in this article makes no sense if the goal is to enhance the standing of women and minorities in the academy. It is nonsensical for a productive faculty member who rightfully champions the equality of women and minorities to deny himself a promotion (and the greater accompanying prestige). If he takes the promotion, his arguments will carry more clout and he will have more power to enact the change that he wishes to see. If he is worried that promotions are competitive and hopes the position might be taken by a woman instead, he should also consider the possibility that the position might be taken by someone who does not care as greatly about furthering equality. The argument seems no different than a 19th-century male suffragist saying that he won t run for president because he is protesting the mistreatment of women. So he denies himself the power to actually enact change and the position instead goes to a sexist who continues the status quo. I really don t follow the logic here. In addition, if you want to play *reductio ad absurdum*, you could argue that men should simply stop taking academic jobs altogether. Doesn t the author s logic actually lead to the conclusion that he should resign? ,
lncRNA CCHE1 increased proliferation, metastasis and invasion of non-small lung cancer cells and predicted poor survival in non-small lung cancer patients
Authors: J Xiang
S Cheng
C Luo
Y Liao
Journal: European review for medical and pharmacological sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Lung cancer; Non-small cell lung cancer; lncRNA; CCHE1; Therapeutic targets
Affiliations: Department of Respiration, University-Town Hospital of Chongqing Medical University, Chongqing, China. .

Abstract:  Objective: Lung cancer is common cancer worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancers. Thus, we studied whether long non-coding RNAs influence malignancy in NSCLC to discover new therapeutic targets for increasing the survival rate of NSCLC patients. lncRNA has been proven to be important in different cancer progression. In this study, we mainly focused on the role of lncRNA CCHE1 (cervical carcinoma high expressed 1) expressed PCNA regulatory lncRNA in NSCLC cancer. Patients and methods: qRT-PCR was used to detect the expression of CCHE1 in 126 cases of NSCLC tissue and adjacent tissue, and the clinical significance was also analyzed. Cell Counting Kit-8 (CCK8) assay was used to detect the proliferation ability of NSCLC cancer cell lines, and Western-blot was used to measure the expression of the protein when the expression of CCHE1 was suppressed. Results: We found that the CCHE1 was highly expressed in the NSCLC tissue, compared with the adjacent tissue. We also found that the expression of CCHE1 was closely related to the size and survival time of patients. Moreover, CCHE1 could promote the proliferation, metastasis, and invasion of NSCLC cell line via increasing the expression of ERK/MAPK signaling pathway. Conclusions: According to the results, we found that CCHE1 was closely related the progression of NSCLC, which could be a potential target for treating NSCLC. 

Retracted: No

PubPeer comments:
 It is hard to believe how this paper slipped through the peer-reviewing and editorial control. The micrographs make you feel sea sick and then it is reason to believe that something is wrong. If you zoom in and look at the details, you will see that areas in the micrographs have been duplicated. Please see rectangles and circles (solid line = two identical areas marked separately; dotted line=area where you see two duplicated areas together). I have included just some examples from Figure 2, 4 and 6. ![file] ![file] ,
THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma
Authors: Jonathan Shuntong Sham
Nancy Wang
Lance Miller
Eric J Stanbridge
Edison Tak-Bun Liu
Dan Xie
Mande Kuppusamy Kumaran
Yan Fang
Hong Lok Lung
Dhinoth Kumar Bangarusamy
Yue Cheng
Liqiong Li
Maria Li Lung
Arthur Kwok Leung Cheung
Eugene R Zabarovsky
Xin-Yuan Guan
Alexey I Protopopov
Sai Wah Tsao
Journal: Oncogene (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: oligonucleotide microarray analysis; THY1; nasopharyngeal carcinoma; downregulated expression; tumour suppressor gene
Affiliations: Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (SAR), People's Republic of China.

Abstract:  Using oligonucleotide microarray analysis, THY1, mapping close to a previously defined 11q22-23 nasopharyngeal carcinoma (NPC) critical region was identified as showing consistent downregulated expression in the tumour segregants, as compared to their parental tumour-suppressing microcell hybrids (MCHs). Gene expression and protein analyses show that THY1 was not expressed in the NPC HONE1 recipient cells, tumour segregants, and other NPC cell lines; THY1 was exclusively expressed in the non-tumourigenic MCHs. The mechanism of THY1 gene inactivation in these cell lines was attributed to hypermethylation. Clinical study showed that in 65% of NPC specimens there was either downregulation or loss of THY1 gene expression. Using a tissue microarray and immunohistochemical staining, 44% of the NPC cases showed downregulated expression of THY1 and 9% lost THY1 expression. The frequency of THY1 downregulated expression in lymph node metastatic NPC was 63%, which was significantly higher than in the primary tumour (33%). After transfection of THY1 gene into HONE1 cells, a dramatic reduction of colony formation ability was observed. These findings suggest that THY1 is a good candidate tumour suppressor gene in NPC, which is significantly associated with lymph node metastases. 

Retracted: No

PubPeer comments:
null, 
 I would also note for other readers that a coauthor on this paper appears to have more than a [dozen papers] with similar concerns. ,
The transforming acidic coiled coil 3 protein is essential for spindle-dependent chromosome alignment and mitotic survival
Authors: Roland P Piekorz
Bernd Nürnberg
Helmut Hanenberg
Wiebke Wetzel
Paula Rio
Leonid Schneider
Frank Essmann
Anja Kletke
Klaus Schulze-Osthoff
Journal: Journal of Biological Chemistry (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: TACC3; mitotic spindle; cell proliferation; mitotic progression; cell survival
Affiliations: Institut für Biochemie und Molekularbiologie II, Universitätsklinikum der Heinrich-Heine-Universität, 40225 Düsseldorf, Germany.

Abstract:  Cancer-associated centrosomal transforming acidic coiled coil (TACC) proteins are involved in mitotic spindle function. By employing gene targeting, we have recently described a nonredundant and essential role of TACC3 in regulating cell proliferation. In this study, we used an inducible RNA interference approach to characterize the molecular function of TACC3 and its role in mitotic progression and cell survival. Our data demonstrate that a TACC3 knockdown arrests G(1) checkpoint-compromised HeLa cells prior to anaphase with aberrant spindle morphology and severely misaligned chromosomes. Interestingly, TACC3-depleted cells fail to accumulate the mitotic kinase Aurora B and the checkpoint protein BubR1 to normal levels at kinetochores. Moreover, localization of the structural protein Ndc80 at outer kinetochores is reduced, indicating a defective kinetochore-microtubule attachment in TACC3-deficient cells. As a consequence of prolonged TACC3 depletion, cells undergo caspase-dependent cell death that relies on a spindle checkpoint-dependent mitotic arrest. TACC3 knockdown cells that escape from this arrest by mitotic slippage become highly polyploid and accumulate supernumerary centrosomes. Similarly, deficiency of the post-mitotic cell cycle inhibitor p21(WAF) exacerbates the effects of TACC3 depletion. Our findings therefore point to an essential role of TACC3 in spindle assembly and cellular survival and identify TACC3 as a potential therapeutic target in cancer cells. 

Retracted: No

PubPeer comments:
null, 
null, 
 ![file] Experiments are the same but p values are different in thesis and publication. How is that possible? , 
 #6 Thlaspi Perfoliatum , what exactly confuses you? That one version has a star on it, the other has not? Schneider removed the star at T0, for whatever reason, maybe because he found highlighting significance at that time point 0 confusing. If you want an exact scientific explanation, contact me by email: https: forbetterscience.com about , 
 Also no significant differences at 2 h between groups in the G1 (2N) graph? That s odd... , 
null, 
 First author: All Western Blots as well as the assembly of the final figures in this paper were done by me  So, first author could explain how  beta-actin in fig 4 C was used as loading control . Loading controls must be probed in the same gel but according to the shapes, it doesn t seem that. ![imag] ,
Na+/K+‑ATPase DR region‑specific antibody protects U251 cells against hypoxia reperfusion‑induced injury via the PI3K/AKT and ERK pathways
Authors: Huilin Gong
Dandong Li
Jin Zheng
Jiangwei Zhang
Pengbiao Lü
Jinning Song
Journal: Molecular Medicine Reports (2017)
Discipline: CLINICAL MEDICINE
Keywords: Cerebral ischemia; Na+/K+-ATPase; DRSAb; astrocytes; PI3K/AKT
Affiliations: Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China., Department of Oncological and Thoracic Surgery, Hanzhong People's Hospital, Hanzhong, Shaanxi 723000, P.R. China., Hospital of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China., Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Abstract:  Cerebral ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and to the death of brain tissue or cerebral infarction/ischemic stroke. In the present study, an Na+/K+‑ATPase (NKA) DR region‑specific antibody (DRSAb) was established and purified and it was demonstrated that DRSAb induced a protective effect on human astrocytes (U251) via the phosphoinositide 3‑kinase (PI3K)/AKT and extracellular signal‑regulated protein kinase (ERK) signaling pathways. The binding of DRSAb on NKA was revealed using flow cytometry. High signals were detected on U251 cells incubated with DRSAb, but not with control sera or BSA. The viability of the hypoxia/reperfusion (H/R)‑treated cells was markedly increased by DRSAb administration of 0.3‑0.5 µM. The optimal concentration of DRSAb was 0.4 µM for attenuation of the injury induced by H/R. The administration of 0.4 µM DRSAb markedly reduced the number of apoptotic cells compared with control sera. The application of PD98059, an ERK inhibitor, and LY‑294002, an AKT inhibitor, attenuated the protective effect induced by DRSAb in the U251 cells subjected to H/R. Furthermore, the application of LY294002 prior to incubation with DRSAb eliminated the activation of ERK1/2, whereas the use of PD98059 failed to attenuate the effect of DRSAb on PI3K/AKT activation. These results indicated that the protective effects of DRSAb against H/R injury in U251 cells occurred via stimulation of the PI3K/AKT and ERK signaling pathways. 

Retracted: No

PubPeer comments:
 There seems to be image duplication in the flow cytometry plots of Figure 2C. Thank you to Dr. Elisabeth Bik for helping me identify the duplicated regions. ![file] ,
The dual control of TFIIB recruitment by NC2 is gene specific
Authors: Martine A Collart
Sandrine Creton
Elisa Leimgruber
Patrick Masson
Journal: Nucleic Acids Research (2008)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NC2; transcription factors; gene expression; TFIIB; histone-fold motif

Abstract:  Negative co-factor 2 (NC2) is a conserved eukaryotic complex composed of two subunits, NC2alpha (Drap1) and NC2beta (Dr1) that associate through a histone-fold motif. In this work, we generated mutants of NC2, characterized target genes for these mutants and studied the assembly of NC2 and general transcription factors on target promoters. We determined that the two NC2 subunits mostly function together to be recruited to DNA and regulate gene expression. We found that NC2 strongly controls promoter association of TFIIB, both negatively and positively. We could attribute the gene-specific repressor effect of NC2 on TFIIB to the C-terminal domain of NC2beta, and define that it requires ORF sequences of the target gene. In contrast, the positive function of NC2 on TFIIB targets is more general and requires adequate levels of the NC2 histone-fold heterodimer on promoters. Finally, we determined that NC2 becomes limiting for TATA-binding protein (TBP) association with a heat inducible promoter under heat stress. This study demonstrates an important positive role of NC2 for formation of the pre-initiation complex on promoters, under normal conditions through control of TFIIB, or upon activation by stress via control of TBP. 

Retracted: No

PubPeer comments:
 Figure 1A * Red boxes: The 37C and 16C panels appear to look very similar. ![file] ,
Adenosine metabolism and murine strain-specific IL-4-induced inflammation, emphysema, and fibrosis
Authors: Michael R Blackburn
Richard P Lifton
Wei Liu
Lynn Boyden
Robert J Homer
Jack A Elias
Richard A Flavell
Chun Geun Lee
Chun-Xiao Sun
Hays W Young
Bing Ma
Journal: Journal of Clinical Investigation (2006)
Discipline: CLINICAL MEDICINE
Keywords: IL-4; tissue effects; Balb/c; C57BL/6 mice; eosinophilic inflammation
Affiliations: Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, Connecticut 06519, USA.

Abstract:  To define the factors that control the tissue effects of IL-4, we compared the effects of Tg IL-4 in Balb/c and C57BL/6 mice. In the former, IL-4 caused modest eosinophilic inflammation and mild airway fibrosis and did not shorten survival. In C57BL/6 mice, IL-4 caused profound eosinophilic inflammation, airway fibrosis, emphysematous alveolar destruction, and premature death. These differences could not be accounted for by changes in Th2 or Th1 cytokines, receptor components, STAT6 activation, MMPs, or cathepsins. In contrast, in C57BL/6 mice, alveolar remodeling was associated with decreased levels of tissue inhibitors of metalloproteinase 2, -3, and -4 and alpha1-antitrypsin, and fibrosis was associated with increased levels of total and bioactive TGF-beta1. Impressive differences in adenosine metabolism were also appreciated, with increased tissue adenosine levels and A(1), A(2B), and A(3) adenosine receptor expression and decreased adenosine deaminase (ADA) activity in C57BL/6 animals. Treatment with ADA also reduced the inflammation, fibrosis, and emphysematous destruction and improved the survival of C57BL/6 Tg animals. These studies demonstrate that genetic influences control IL-4 effector pathways in the murine lung. They also demonstrate that IL-4 has different effects on adenosine metabolism in Balb/c and C57BL/6 mice and that these differences contribute to the different responses that IL-4 induces in these inbred animals. 

Retracted: No

PubPeer comments:
 This July 2019 paper has been withdrawn in September 2019. The original paper PDF has been removed from the journal s website, but has been archived here: https: web.archive.org web 20190803143008 https: www.europeanreview.org wp wp-content uploads 5949-5957.pdf ,
NGF controls APP cleavage by downregulating APP phosphorylation at Thr668: relevance for Alzheimer's disease
Authors: Raffaele Maletta
Chiara Cupidi
Pietro Calissano
Robert Nisticò
Amalia C Bruni
Giulia Bolasco
Viviana Triaca
Nadia Canu
Valentina Sposato
Maria Teresa Ciotti
Piergiuseppe Pelicci
Marco Feligioni
Journal: Aging cell (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AD; APP pT668; BACE; NGF; ShcC
Affiliations: Institute of Cell Biology and Neuroscience, National Research Council (CNR), Rome, Italy., European Brain Research Institute (EBRI Foundation), Rome, Italy., European Molecular Biology Laboratory (EMBL), Monterotondo, Italy., European Institute of Oncology (IFOM-IEO), Milan, Italy., Regional Neurogenetic Center (CRN), ASP Catanzaro, Lamezia Terme, Italy., Department of System Medicine, University of Rome "Tor Vergata", Rome, Italy.

Abstract:  NGF has been implicated in forebrain neuroprotection from amyloidogenesis and Alzheimer's disease (AD). However, the underlying molecular mechanisms are still poorly understood. Here, we investigated the role of NGF signalling in the metabolism of amyloid precursor protein (APP) in forebrain neurons using primary cultures of septal neurons and acute septo-hippocampal brain slices. In this study, we show that NGF controls the basal level of APP phosphorylation at Thr668 (T668) by downregulating the activity of the Ser/Thr kinase JNK(p54) through the Tyr kinase signalling adaptor SH2-containing sequence C (ShcC). We also found that the specific NGF receptor, Tyr kinase A (TrkA), which is known to bind to APP, fails to interact with the fraction of APP molecules phosphorylated at T668 (APP(pT668) ). Accordingly, the amount of TrkA bound to APP is significantly reduced in the hippocampus of ShcC KO mice and of patients with AD in which elevated APP(pT668) levels are detected. NGF promotes TrkA binding to APP and APP trafficking to the Golgi, where APP-BACE interaction is hindered, finally resulting in reduced generation of sAPPβ, CTFβ and amyloid-beta (1-42). These results demonstrate that NGF signalling directly controls basal APP phosphorylation, subcellular localization and BACE cleavage, and pave the way for novel approaches specifically targeting ShcC signalling and/or the APP-TrkA interaction in AD therapy. 

Retracted: No

PubPeer comments:
 Beta-actin bands are identical in Fig. 1A and 2E: ![file] Beta-actin bands are highly similar in Fig. 2A and D, but different groups were used for the third band: ![file] Beta-actin bands are identical in Fig. 3B and D: ![file] ,
IKAP/Elp1 involvement in cytoskeleton regulation and implication for familial dysautonomia
Authors: Channa Maayan
Miguel Weil
Gil Ast
Rachel Cohen-Kupiec
David Cheishvili
Aharon Razin
Sharon Lefler
Journal: Human Molecular Genetics (2011)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: IKAP/Elp1; familial dysautonomia; sensory neuropathy; transcriptional elongation; cytoplasm
Affiliations: Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel.

Abstract:  Deficiency in the IKAP/Elp1 protein leads to the recessive sensory autosomal congenital neuropathy which is called familial dysautonomia (FD). This protein was originally identified as a role player in transcriptional elongation being a subunit of the RNAPII transcriptional Elongator multi-protein complex. Subsequently, IKAP/Elp1 was shown to play various functions in the cytoplasm. Here, we describe experiments performed with IKAP/Elp1 downregulated cell lines and FD-derived cells and tissues. Immunostaining of the cytoskeleton component α-tubulin in IKAP/Elp1 downregulated cells revealed disorganization of the microtubules (MTs) that was reflected in aberrant cell shape and process formation. In contrast to a recent report on the decrease in α-tubulin acetylation in IKAP/Elp1 downregulated cells, we were unable to observe any effect of IKAP/Elp1 deficiency on α-tubulin acetylation in the FD cerebrum and in a variety of IKAP/Elp1 downregulated cell lines. To explore possible candidates involved in the observed aberrations in MTs, we focused on superior cervical ganglion-10 protein (SCG10), also called STMN2, which is known to be an MT destabilizing protein. We have found that SCG10 is upregulated in the IKAP/Elp1-deficient FD cerebrum, FD fibroblasts and in IKAP/Elp1 downregulated neuroblastoma cell line. To better understand the effect of IKAP/Elp1 deficiency on SCG10 expression, we investigated the possible involvement of RE-1-silencing transcription factor (REST), a known repressor of the SCG10 gene. Indeed, REST was downregulated in the IKAP/Elp1-deficient FD cerebrum and IKAP/Elp1 downregulated neuroblastoma cell line. These results could shed light on a possible link between IKAP/Elp1 deficiency and cytoskeleton destabilization. 

Retracted: No

PubPeer comments:
 Figure 3D. Splicing in 2 panels, but no splicing in 2 other panels. https: imgur.com 8u4xvl2 ,
Crystal structure of the 65-kilodalton heat shock protein, chaperonin 60.2, of Mycobacterium tuberculosis
Authors: Shekhar C Mande
Rohini Qamra
Journal: Journal of Bacteriology (2004)
Discipline: MICROBIOLOGY
Keywords: Chaperonin 60s; proteins; folding; assembly; ATP-dependent
Affiliations: Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad 500076, India., Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad, India

Abstract:  Chaperonin 60s are a ubiquitous class of proteins that promote folding and assembly of other cellular polypeptides in an ATP-dependent manner. The oligomeric state of chaperonin 60s has been shown to be crucial to their role as molecular chaperones. Chaperonin 60s are also known to be important stimulators of the immune system. Mycobacterium tuberculosis possesses a duplicate set of chaperonin 60s, both of which have been shown to be potent cytokine stimulators. The M. tuberculosis chaperonin 60s are present in the extracellular milieu at concentrations that are extremely low for the formation of an oligomer. Here we present the crystal structure of one of the chaperonin 60s of M. tuberculosis, also called Hsp65 or chaperonin 60.2, at 3.2-A resolution. We were able to crystallize the protein in its dimeric state. The unusual dimerization of the protein leads to exposure of certain hydrophobic patches on the surface of the protein, and we hypothesize that this might have relevance in binding to immunogenic peptides, as it does in the eukaryotic homologs. 

Retracted: No

PubPeer comments:
 Figure 7 c - The left and right lanes in the panel for the pAMPK appear to be duplications. One image is rotated 180 degrees along the horizontal axis. This is illustrated in the enlarged image with the left and right sides of the images aligned and the right image flipped top to bottom. The contrast and brightness in the enlarged image have been adjusted to demonstrate the shared features. ![file] ![file] Figure 7 b and c - The same image has been used to represent AKT (panel b) and AMPK (panel c). Contrast and brightness have been adjusted in the enlarged images to demonstrate shared features. ![file] ,
Multicompartmental, multilayered probucol microcapsules for diabetes mellitus: Formulation characterization and effects on production of insulin and inflammation in a pancreatic β-cell line
Authors: Armin Mooranian
Hani Al-Salami
Rebecca Negrulj
Frank Arfuso
Journal: Artificial Cells Nanomedicine and Biotechnology (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: NIT-1 β-cells; artificial-cell microencapsulation; bile acids; diabetes mellitus; inflammation
Affiliations: a Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University , Perth, Western Australia, Australia., b Stem Cell and Cancer Biology Laboratory, School of Biomedical Science, Curtin Health Innovation Research Institute, Curtin University , Perth Western Australia, Australia.

Abstract:  Context: We have shown that the primary bile acid, cholic acid (CA), has anti-diabetic effects in vivo. Probucol (PB) is a lipophilic drug with potential applications in type 2 diabetes (T2D). Objective: This study aimed to encapsulate CA with PB and examine the formulation and surface characteristics of the microcapsules. We also tested the microcapsules' biological effects on pancreatic β-cells. Methods: Using the polymer, sodium alginate (SA), two formulations were prepared: PB-SA (control), and PB-CA-SA (test). Complete characterizations of the morphology, shape, size, chemical, thermal, and rheological properties, swelling and mechanical strength, cross-sectional imaging (Micro CT), stability, Zeta-potential, drug contents, and PB release profile were carried out, at different temperature and pH values. The microcapsules were applied to a NIT-1 cell culture and the supernatant was analyzed for insulin and TNF-α concentrations. Results: CA incorporation optimized the PB microcapsules, which exhibited pseudoplastic-thixotropic rheological characteristics. The size of the microcapsules remained similar after CA addition, and the microcapsules showed even drug distribution and no chemical alterations of the excipients. Micro-CT imaging, differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy showed consistent microcapsules with uniform shape and morphology. PB-CA-SA microcapsules enhanced NIT-1 cell viability under hyperglycemic states and resulted in improved insulin release as well as reduced cytokine production at the physiological glucose levels. Conclusions: The addition of the primary bile acid, CA, improved the physical properties of the microcapsules and enhanced their pharmacological activity in vitro, suggesting potential applications in diabetes treatment. 

Retracted: No

PubPeer comments:
 In the article, Figure 1a and Figure 1b appear to be the same sample imaged at slightly different planes of focus. ![file] ,
LncRNA TTN-AS1 sponges miR-376a-3p to promote colorectal cancer progression via upregulating KLF15
Authors: Yan Xiong
Zhimin Qiu
Xiaoliang Cheng
Yanhua Wang
Rongfeng Song
Fang Jiang
Journal: Life Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Colorectal cancer; KLF15; LncRNA TTN-AS1; miR-376a-3p.
Affiliations: Department of Internal Medicine of Digestive Tumors, Jiangxi Provincial Cancer Hospital, China., Department of Thoracic Surgery, Jiangxi Provincial Cancer Hospital, China., Department of Comprehensive Oncology Medicine, Jiangxi Provincial Cancer Hospital, China., Department of Internal Medicine of Digestive Tumors, Jiangxi Provincial Cancer Hospital, China. Electronic address: .

Abstract:  Aims: Long non-coding RNAs (lncRNAs) play key roles in regulating multiple cancers. TTN-AS1 was reported to function in several human malignancies. However, the biological function of TTN-AS1 in colorectal cancer (CRC) has not been explored. In this study, we aimed to investigate the role and the underlying mechanisms of TTN-AS1 in CRC progression. Main methods: RT-qPCR was used to detect the expression levels of TTN-AS1, miR-376a-3p and KLF15 in colorectal cancer tissues and cells. CCK-8, colony formation, flow cytometry and transwell assays were performed to determine the cell proliferation, apoptotic rate and invasion ability. Target genes were predicted using bioinformatics methods. si-RNA and miRNA inhibitor were transfected into CRC cells to explore the underlying mechanisms. Tumor xenografts were created to confirm the function of TTN-AS-1 in vivo. Key findings: TTN-AS1 upregulation was observed both in CRC tissues and cell lines. Functional investigation showed that knockdown of TTN-AS1 inhibited CRC cell proliferation and invasion, while enhanced cell apoptosis. Bioinformatics analysis identified miR-376a-3p as a target of TTN-AS1. Transfection of miR-376a-3p inhibitor mitigated the alterations induced by TTN-AS1 knockdown. Moreover, TTN-AS1 positively regulated KLF15 via sponging miR-376a-3p. Additionally, these findings were supported by in vivo experiments. Significance: In conclusions, TTN-AS1 promoted CRC proliferation and invasion through miR-376a-3p/KLF15 axis. Our findings suggested that TTN-AS1 might be a potential therapeutic target in CRC treatment. 

Retracted: No

PubPeer comments:
 I hope Table 1 was fixed in the final version. ![file] I have marked the two sections where the numbers in the Low- and High-TTN-AS1 do add up to 27 and 13 respectively. ,
Alternative oxidase encoded by sequence-optimized and chemically-modified RNA transfected into mammalian cells is catalytically active
Authors: Howard T Jacobs
Norbert Weissmann
Marten Szibor
Alireza Seraji
Carsten Rudolph
Luca Giordano
Nasim Alebrahimdehkordi
Natascha Sommer
Christian Plank
Manish K Aneja
Journal: Gene Therapy (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Plants; organisms; alternative oxidase; AOX; metabolic stresses
Affiliations: Faculty of Medicine and Health Technology, FI-33014 Tampere University Hospital, Tampere University of Applied Sciences (TUNI), Tampere, Finland. ., Ethris GmbH, DE-82152, Planegg, Germany., Excellence Cluster Cardio-Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, D-35392, Giessen, Germany., Faculty of Medicine and Health Technology, FI-33014 Tampere University Hospital, Tampere University of Applied Sciences (TUNI), Tampere, Finland.

Abstract:  Plants and other organisms, but not insects or vertebrates, express the auxiliary respiratory enzyme alternative oxidase (AOX) that bypasses mitochondrial respiratory complexes III and/or IV when impaired. Persistent expression of AOX from Ciona intestinalis in mammalian models has previously been shown to be effective in alleviating some metabolic stresses produced by respiratory chain inhibition while exacerbating others. This implies that chronic AOX expression may modify or disrupt metabolic signaling processes necessary to orchestrate adaptive remodeling, suggesting that its potential therapeutic use may be confined to acute pathologies, where a single course of treatment would suffice. One possible route for administering AOX transiently is AOX-encoding nucleic acid constructs. Here we demonstrate that AOX-encoding chemically-modified RNA (cmRNA), sequence-optimized for expression in mammalian cells, was able to support AOX expression in immortalized mouse embryonic fibroblasts (iMEFs), human lung carcinoma cells (A549) and primary mouse pulmonary arterial smooth muscle cells (PASMCs). AOX protein was detectable as early as 3 h after transfection, had a half-life of ~4 days and was catalytically active, thus supporting respiration and protecting against respiratory inhibition. Our data demonstrate that AOX-encoding cmRNA optimized for use in mammalian cells represents a viable route to investigate and possibly treat mitochondrial respiratory disorders. 

Retracted: No

PubPeer comments:
 Supplementary Figure 2: The GAPDH and u03b1-tubulin rows appear to be duplicated. I increased the contrast below to make it more obvious. If you zoom in, you can see the noise matches exactly. Would the authors please comment? ![file] ,
Id2 Mediates Tumor Initiation, Proliferation, and Angiogenesis in Rb Mutant Mice
Authors: Gerson Rothschild
Antonio Iavarone
Yoshifumi Yokota
Anna Lasorella
Robert G Russell
Journal: Molecular and Cellular Biology (2005)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Id2; retinoblastoma; pituitary tumors; proliferation; differentiation
Affiliations: Institute for Cancer Genetics, Columbia University, 1150 St. Nicholas Avenue, New York, NY 10032, USA., Institute for Cancer Genetics, Department of Biochemistry, Fukui Medical University, Fukui Japan, Lombardi Cancer Center, Department of Oncology, Georgetown University, Washington, DC, Department of Pathology, Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, New York

Abstract:  The inhibitor of differentiation Id2 is a target of the retinoblastoma (Rb) protein during mouse embryogenesis. In Rb(+/-) mice, LOH at the wild-type Rb allele initiates pituitary adenocarcinoma, a tumor derived from embryonic melanotropes. Here we identify a critical role for Id2 in initiation, growth, and angiogenesis of pituitary tumors from Rb(+/-) mice. We show that proliferation and differentiation are intimately coupled in Rb(+/-) pituitary cells before tumor initiation. In Id2-null pituitaries, premature activation of basic helix-loop-helix-mediated transcription and expression of the cdk inhibitor p27(Kip1) impairs the proliferation of melanotropes and tumor initiation. Without Id2, Rb(+/-) mice have fewer early tumor lesions and a markedly decreased proliferation rate of the tumor foci. Expression of Id2 by pituitary tumor cells promotes growth and angiogenesis by functioning as a master regulator of vascular endothelial growth factor (VEGF). In human neuroblastoma, the N-Myc-driven expression of Id2 is sufficient and necessary for expression of VEGF. These results establish that aberrant Id2 activity directs initiation and progression of embryonal cancer. 

Retracted: No

PubPeer comments:
 ![file] Presence of an apparently repetitive pattern in Figure 3 ,
The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1
Authors: Yasemin Sancak
Robert A Lindquist
Yoav D Shaul
Timothy R Peterson
David M Sabatini
Liron Bar-Peled
Carson C Thoreen
Journal: Science (2008)
Discipline: Multidisciplinary
Keywords: mTORC1; Rag proteins; GTPases; amino acids; cancer
Affiliations: Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology (MIT), Nine Cambridge Center, Cambridge, MA 02142, USA.

Abstract:  The multiprotein mTORC1 protein kinase complex is the central component of a pathway that promotes growth in response to insulin, energy levels, and amino acids and is deregulated in common cancers. We find that the Rag proteins--a family of four related small guanosine triphosphatases (GTPases)--interact with mTORC1 in an amino acid-sensitive manner and are necessary for the activation of the mTORC1 pathway by amino acids. A Rag mutant that is constitutively bound to guanosine triphosphate interacted strongly with mTORC1, and its expression within cells made the mTORC1 pathway resistant to amino acid deprivation. Conversely, expression of a guanosine diphosphate-bound Rag mutant prevented stimulation of mTORC1 by amino acids. The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb. 

Retracted: No

PubPeer comments:
 Figure 3. The pattern of FLAG-RagB Rap2A Rheb1 bands when you compare Fig. 3B and 3C is surprisingly similar. They differ very little in the contrast of the bands. This could be explained by different expositions. Could authors check if any of these images were inadvertently used? ![file] ,
Incunabular immunological events in prion trafficking
Authors: Anne Avery
Theodore Johnson
Brady Michel
Steven Dow
Mark D Zabel
Glenn Telling
Crystal Meyerett-Reid
Bruce Pulford
Heather Bender
Christy Wyckoff
Adam Ferguson
Journal: Scientific Reports (2012)
Discipline: Multidisciplinary
Keywords: prions; innate immune system; lymphotropic; intranodal prion trafficking; fluorescent prions
Affiliations: College of Veterinary Medicine and Biomedical Sciences, Department of Microbiology, Immunology and Pathology, Prion Research Program at Colorado State University, Fort Collins, Colorado 80521, USA.

Abstract:  While prions probably interact with the innate immune system immediately following infection, little is known about this initial confrontation. Here we investigated incunabular events in lymphotropic and intranodal prion trafficking by following highly enriched, fluorescent prions from infection sites to draining lymph nodes. We detected biphasic lymphotropic transport of prions from the initial entry site upon peripheral prion inoculation. Prions arrived in draining lymph nodes cell autonomously within two hours of intraperitoneal administration. Monocytes and dendritic cells (DCs) required Complement for optimal prion delivery to lymph nodes hours later in a second wave of prion trafficking. B cells constituted the majority of prion-bearing cells in the mediastinal lymph node by six hours, indicating intranodal prion reception from resident DCs or subcapsulary sinus macrophages or directly from follicular conduits. These data reveal novel, cell autonomous prion lymphotropism, and a prominent role for B cells in intranodal prion movement. 

Retracted: No

PubPeer comments:
 This preprint appears to be computer-generated with [SCIgen] . ![file] --- This comment was written by Guillaume Cabanac and Cyril Labbu00e9. Contact: [SeekAndBlastn-Operators@univ-grenoble-alpes.fr](mailto:SeekAndBlastn-Operators@univ-grenoble-alpes.fr). ,
Effects of TLR4 gene silencing on the proliferation and apotosis of hepatocarcinoma HEPG2 cells
Authors: Baolong Wang
Yating Liu
Yuanhong Xu
Tao Li
Min Zhou
Jilong Shen
Enjun Xu
Journal: Oncology Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: HepG2; TLR4; cell apoptosis; cell proliferation; siRNA.
Affiliations: Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China., ICU, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China., Department of Clinical Laboratory, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China., Anhui Provincial Laboratory of Pathogen and Biology Zoonoses, Anhui Medical University, Hefei, Anhui 230022, P.R. China.

Abstract:  Toll-like receptors (TLRs) are key factors in the innate immune system and initiate an inflammatory response to foreign pathogens, such as bacteria, fungi and viruses. TLR4-mediated signaling has been implicated in tumor cell proliferation and apoptosis in numerous cancers. The present study aimed to investigate the biological effect of TLR4 on the proliferation and apoptosis of human liver cancer cells and the mechanisms responsible for the regulation of cellular responses following TLR4 gene knockdown. Three TLR4 small interfering (si)RNA constructs, consisting of TLR4-siRNA-1, TLR4-siRNA-2 and TLR4-siRNA-3, were transiently transfected into HepG2 cells using Lipofectamine 2000. TLR4 knockdown was confirmed using reverse transcription-polymerase chain reaction and western blotting. The effect of the TLR4 siRNA on tumor cell proliferation was monitored by methyl thiazolyl tetrazolium assay and cell apoptosis was observed by flow cytometry. The expression of TLR4-associated proteins, consisting of myeloid differentiation primary response 88 (MyD88), Toll-interleukin-1R-domain-containing adapter-inducing interferon-β (TRIF), interferon regulatory factor-3 (IRF3), nuclear factor (NF)-κB, NF-κB inhibitor α (IκBα), phosphorylated IκBα (p-IκBα), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), was detected by western blot analysis. TLR4-siRNA-1 had the strongest knockdown effect and inhibited TLR4 messenger RNA and protein expression. TLR4 knockdown with TLR4-siRNA-1 reduced cell proliferation and promoted cell apoptosis. MyD88, TRIF, IRF3, IκBα, JNK and ERK were markedly suppressed in the cells transfected with TLR4 siRNA. However, nuclear expression of NF-κB and p-IκBα increased in HepG2 cells with TLR4 gene knockdown. The present study revealed that TLR4-mediated signaling plays a key role in the proliferation and apoptosis of cultured hepatocarcinoma cells. Therefore, RNA interference-directed targeting of TLR4 may raise the potential of the application of TLR4 knockdown for liver cancer therapy. 

Retracted: No

PubPeer comments:
 Figure 4A: * Blue boxes: Unexpected similarities between two panels. ![file] ,
Seedling Establishment of Tall Fescue Exposed to Long-Term Starvation Stress
Authors: Sara Stefanini
Claudia Roberta Damiani
Thais Huarancca Reyes
Lorenzo Guglielminetti
Antonio Pompeiano
Marco Volterrani
Paolo Vernieri
Journal: PLoS ONE (2016)
Discipline: Multidisciplinary
Keywords: germinating seeds; cotyledons; carbohydrates balance; seedling vigor; tall fescue
Affiliations: Laboratory of Ecological Plant Physiology, Global Change Research Institute CAS, Brno, Czech Republic., Federal University of Grande Dourados, Dourados, Brazil., Department of Agriculture, Food and Environment, University of Pisa, Pisa, Italy.

Abstract:  In germinating seeds under unfavorable environmental conditions, the mobilization of stores in the cotyledons is delayed, which may result in a different modulation of carbohydrates balance and a decrease in seedling vigor. Tall fescue (Festuca arundinacea Schreb.) caryopses grown at 4°C in the dark for an extended period in complete absence of nutrients, showed an unexpected ability to survive. Seedlings grown at 4°C for 210 days were morphologically identical to seedlings grown at 23°C for 21 days. After 400 days, seedlings grown at 4°C were able to differentiate plastids to chloroplast in just few days once transferred to the light and 23°C. Tall fescue exposed to prolonged period at 4°C showed marked anatomical changes: cell wall thickening, undifferentiated plastids, more root hairs and less xylem lignification. Physiological modifications were also observed, in particular related to sugar content, GA and ABA levels and amylolytic enzymes pattern. The phytohormones profiles exhibited at 4 and 23°C were comparable when normalized to the respective physiological states. Both the onset and the completion of germination were linked to GA and ABA levels, as well as to the ratio between these two hormones. All plants showed a sharp decline in carbohydrate content, with a consequent onset of gradual sugar starvation. This explained the slowed then full arrest in growth under both treatment regimes. The analysis of amylolytic activity showed that Ca2+ played a central role in the stabilization of several isoforms. Overall, convergence of starvation and hormone signals meet in crosstalk to regulate germination, growth and development in tall fescue. 

Retracted: No

PubPeer comments:
 ![file] More similar than expected , 
 #1 Perhaps the issue is a bit broader. ![file] ,