PReD-Bench/PRed-Bench huggingface dataset:
A transcriptomic atlas of mouse cerebellar cortex comprehensively¬†defines cell types
Authors: Caroline Martin
Velina Kozareva
Aviv Regev
Wade G Regehr
Stephanie Rudolph
Chong Guo
Tomas Osorno
Charles Vanderburg
Naeem Nadaf
Evan Macosko
Journal: Nature (2021)
Discipline: Multidisciplinary
Keywords: cerebellar cortex; cell types; molecular profiling; Purkinje neurons; interneurons
Affiliations: Broad Institute of Harvard and MIT, Stanley Center for Psychiatric Research, Cambridge, MA, USA., Department of Neurobiology, Harvard Medical School, Boston, MA, USA., Broad Institute of Harvard and MIT, Stanley Center for Psychiatric Research, Cambridge, MA, USA. .

Abstract:  The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition and autonomic regulation. However, a complete inventory of cerebellar cell types is currently lacking. Here, using recent advances in high-throughput transcriptional profiling1-3, we molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje neurons showed considerable regional specialization, with the greatest diversity occurring in the posterior lobules. For several types of cerebellar interneuron, the molecular variation within each type was more continuous, rather than discrete. In particular, for the unipolar brush cells-an interneuron population previously subdivided into discrete populations-the continuous variation in gene expression was associated with a graded continuum of electrophysiological properties. Notably, we found that molecular layer interneurons were composed of two molecularly and functionally distinct types. Both types show a continuum of morphological variation through the thickness of the molecular layer, but electrophysiological recordings revealed marked differences between the two types in spontaneous firing, excitability and electrical coupling. Together, these findings provide a comprehensive cellular atlas of the cerebellar cortex, and outline a methodological and conceptual framework for the integration of molecular, morphological and physiological ontologies for defining brain cell types. 

Retracted: No

PubPeer comments:
 After I investigated the raw read count data published in this paper, I found that Malat1 is abundantly expressed in nearly all the cell types clustered in this paper as you can see in the figure.  For most of the cell types, Malat1 occupied 25%-85% of the Umi count and is also 2-100 fold higher than the second highly expressed gene in each cell type. In the meantime, Purkinje cells also occupied a large portion of the Umi count in all the cell types. It can be partially explained by the fact that Malat1 is a nucleus enriched long noncoding RNA and the Purkinje cell is the largest neuron in the cerebellum. However, the bias of umi count in either Malat1 and Purkinje cells cannot be observed in other single nuclei sequencing studies. Can the authors of this paper explain why does this bias exist in this dataset? Thank you. ,
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
Authors: Robert D Bell
Jan Sallstrom
Christer Betsholtz
Abhay P Sagare
Berislav V Zlokovic
Rashid Deane
Itender Singh
David M Holtzman
Ethan A Winkler
Zhenhua Wu
Bradford C Berk
Annika Armulik
Journal: Nature (2012)
Discipline: Multidisciplinary
Keywords: APOE4; Alzheimer's disease; neurovascular dysfunction; blood-brain barrier; CypA
Affiliations: Center for Neurodegenerative and Vascular Brain Disorders, University of Rochester Medical Center, Rochester, New York 14642, USA.

Abstract:  Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4. APOE4 is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage. Neurovascular dysfunction is present in normal APOE4 carriers and individuals with APOE4-associated disorders. In mice, lack of Apoe leads to blood-brain barrier (BBB) breakdown, whereas APOE4 increases BBB susceptibility to injury. How APOE genotype affects brain microcirculation remains elusive. Using different APOE transgenic mice, including mice with ablation and/or inhibition of cyclophilin A (CypA), here we show that expression of APOE4 and lack of murine Apoe, but not APOE2 and APOE3, leads to BBB breakdown by activating a proinflammatory CypA-nuclear factor-Œ∫B-matrix-metalloproteinase-9 pathway in pericytes. This, in turn, leads to neuronal uptake of multiple blood-derived neurotoxic proteins, and microvascular and cerebral blood flow reductions. We show that the vascular defects in Apoe-deficient and APOE4-expressing mice precede neuronal dysfunction and can initiate neurodegenerative changes. Astrocyte-secreted APOE3, but not APOE4, suppressed the CypA-nuclear factor-Œ∫B-matrix-metalloproteinase-9 pathway in pericytes through a lipoprotein receptor. Our data suggest that CypA is a key target for treating APOE4-mediated neurovascular injury and the resulting neuronal dysfunction and degeneration. 

Retracted: No

PubPeer comments:
 This work appears to duplicate other work by the same authors. See example below.  , 
 Regarding the XRD of the pastes, the authors claimed that it contained  Calcium silicate (C2S C3S) . This shows a fundamental misunderstanding of what XRD is and what it shows. Alite (C2S) and belite (C3S) are both technically calcium silicates, but their XRD signatures are distinct. Moreover, their content should be minor at this point in hydration, replaced by their hydrates (which are generally X-ray amorphous). Here, also, the paper displays a lack of understanding. There are peaks marked for  calcium aluminate hydrate and  calcium silicate hydrate, even though these phases would be generally be expected to be X-ray amorphous. It is not stated which mineral phases are supposedly associated with these chemical compositions. Most of the major peaks are also unlabeled.  ,
Leptin and neuropeptide y have opposing modulatory effects on nucleus of the solitary tract neurophysiological responses to gastric loads: implications for the control of food intake
Authors: Gary J Schwartz
Timothy H Moran
Journal: Endocrinology (2002)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Leptin; neuropeptide Y; hypothalamic signaling pathways; food intake control; brain stem
Affiliations: Bourne Behavioral Research Laboratory, Department of Psychiatry, WMC Cornell University (G.J.S.), White Plains, New York 10605, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine (T.H.M.), Baltimore, Maryland 21205

Abstract:  Leptin is an adiposity hormone that modulates the activity of multiple hypothalamic signaling pathways involved in the control of food intake. The present experiments were designed to evaluate whether central administration of leptin or one of its downstream mediators, neuropeptide Y (NPY), could affect food intake by modulating the brain stem neurophysiological response to ascending meal-related feedback signals in the nucleus of the solitary tract (NTS) in anesthetized male Long-Evans rats. NTS neurons at the rostrocaudal level of the area postrema were dose-dependently activated by gastric loads ranging from 2-10 ml, and leptin and NPY had opposite modulatory effects on this load volume/activity relationship: leptin significantly increased NTS responses to gastric loads, whereas NPY reduced the potency and efficacy with which gastric loads activated NTS neurons. These effects were probably not mediated by peripheral effects of centrally administered peptides or by the gastrokinetic effects of central NPY or leptin, because the dose-response relationship between gastric load volume and neurophysiological firing rate was unchanged in gastric load-sensitive vagal afferent fibers. These data suggest a mechanistic framework for considering how feeding behavior occurring in meals is altered by challenges to energy homeostasis, such as fasting and overfeeding. 

Retracted: No

PubPeer comments:
  ,
Increased semaphorin 3c expression promotes tumor growth and metastasis in pancreatic ductal adenocarcinoma by activating the ERK1/2 signaling pathway
Authors: Bing Ni
Ping Bie
Xuejun Xu
Jian Li
Yu You
Shixiang Guo
Songsong Liu
Zhiping Zhao
Huaizhi Wang
Journal: Cancer Letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: EMT; ERK1/2; Pancreatic ductal adenocarcinoma; Sema3c.
Affiliations: Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China., Institute of Immunology, PLA, Third Military Medical University, Chongqing 40038, PR China; Department of Pathophysiology and High Altitude Pathology, Third Military Medical University, Chongqing 400038, PR China. Electronic address: ., Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. Electronic address: .

Abstract:  Pancreatic cancer is characterized by neural alterations and aberrant expression of neural-specific factors. Semaphorins have been recognized as key contributors in axon guidance, the immune response and tumor progression. Recent studies have suggested the involvement of Semaphorin 3c (sema3c) in tumorigenesis and metastasis in numerous types of cancer, however, the clinical significance of sema3c and its role in the growth and metastasis of pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, we found that aberrant sema3c expression was positively associated with a particular tumor stage and correlated with poor survival of PDAC patients. Knockdown of sema3c attenuated proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in a pancreatic cancer cell line and reduced PDAC cell tumorigenesis upon xenotransplantation into NOD/SCID mice. Overexpression of sema3c produced the opposite effects and promoted the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. Overall, our findings demonstrate that aberrant expression of sema3c is correlated with poor prognosis of PDAC patients and promotes tumor growth and metastasis by activating ERK1/2 signaling pathway. 

Retracted: No

PubPeer comments:
 It appears that there are duplicated or overlapping images in figures 4 and 5  ,
Hypersensitivity to chromium-induced DNA damage correlates with constitutive deregulation of upstream p53 kinases in p21‚à?‚à?HCT116 colon cancer cells
Authors: David M Waisman
Haley K Cochrane
Andrew M Leidal
Arthur Chiu
Richard Hill
Laura D Gillis
Patricia A Madureira
Patrick W K Lee
Journal: DNA repair (2008)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: p21; apoptosis; DNA damage; chromium exposure; p53
Affiliations: Department of Microbiology & Immunology, Dalhousie University, Halifax, NS, Canada.

Abstract:  The cyclin-dependent kinase inhibitor p21(CIP1/WAF1) is a key component in cell cycle control and apoptosis, directing an anti-apoptotic response following DNA damage. Chromium exposure resulted in a 500-1000 fold increase in apoptosis-induced cell death in p21-/- HCT116 cells compared to wild-type or p53-/- cells. p53 shRNA (or transient p53 siRNA) into p21-/- HCT116 cells reduced Cr(VI) sensitivity, suggesting the enhanced apoptosis in p21-/- cells is p53-dependent. Under non-DNA damage conditions, the p53 level in p21-/- cells was significantly higher than in wild-type cells, due to enhanced p53 phosphorylation and stabilization rather than elevated p53 transcription. Wild-type cells showed significant p53 protein induction upon DNA damage whereas p21-/- cells showed no p53 increase. p21-/- cells display the constitutive activation of upstream p53 kinases (ATM, DNA-PK, ATR, AKT and p38). 2D gel analysis revealed p53 patterns in p21-/- cells were distinct from those in wild-type cells before and after chromium exposure. Our results suggest that p21 has an important role in the cellular response to normal replicative stress and its absence leads to a "chronic DNA damage" state that primes the cell for p53-dependent apoptosis. 

Retracted: No

PubPeer comments:
 This is one of two papers by the same authors which seem to report identical experimental work, results and conclusions: 1. Beygi, M.H., Kazemi, M.T., Nikbin, I.M., Amiri, J.V., Rabbanifar, S. and Rahmani, E., 2014. The influence of coarse aggregate size and volume on the fracture behavior and brittleness of self-compacting concrete. Cement and Concrete Research, 66, pp.75-90. 2. Beygi, M.H., Kazemi, M.T., Amiri, J.V., Nikbin, I.M., Rabbanifar, S. and Rahmani, E., 2014. Evaluation of the effect of maximum aggregate size on fracture behavior of self compacting concrete. Construction and Building Materials, 55, pp.202-211. The authors submitted these papers to review simultaneously. Examples of duplicate content are shown in the image below. There is a particularly disconcerting facet of this duplication, which is that the authors reported identical results in tabular format, but different results in graphic format, which seems to indicate that the graphic results in Paper 2 were erroneous.  ,
Wild-type Shadoo proteins convert to amyloid-like forms under native conditions
Authors: Serene Wohlgemuth
Joel C Watts
Howard Young
John Paul Glaves
Paul E Fraser
Vivian Ng
David Westaway
Gerold Schmitt-Ulms
Joanne McLaurin
Nathalie Daude
Sacha Genovesi
Journal: Journal of Neurochemistry (2010)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: PrP(C); PrP(Sc); Shadoo; amyloid-like form; Sho
Affiliations: Centre for Prions and Protein Folding Diseases, University of Alberta, Alberta, Canada.

Abstract:  The cellular prion protein PrP(C) refolds into a beta-sheet enriched, infectivity-associated form called PrP(Sc). Shadoo (Sho) is a newly discovered glycoprotein that is also expressed in the adult brain. Wild type (wt) mouse Sho consists of an arginine-rich region, a hydrophobic central domain of five tandem A/LAAG amino acid repeats R1-R5 with similarity to the hydrophobic domain of PrP(C), and a C-terminal domain with one N-linked carbohydrate. As some alanine-rich proteins and PrP with a shortened C-terminal domain form amyloid we investigated conformational properties of wt Sho and polymorphic variants with insertion/deletions centered on R3. Recombinant mouse and sheep Sho converted to an amyloid-like form without recourse to chemical denaturation or acidification. For wt proteins this transition was marked by increased thioflavin T binding, Congo red staining, presence of fibrillar structures by electron microscopy, formation of sodium dodecyl sulfate-resistant complexes and the generation of a C-terminal proteinase K resistant core of 5-8 kDa. Variant Sho proteins differing within the R1-R5 region exhibited most but not all of these properties. Our studies define a proteinase K -resistant signature fragment for the amyloid fold of Sho and raise the question of a physiological role for this form of the wt protein. 

Retracted: No

PubPeer comments:
 Identified by another reader. ***  ,
Retracted Article: A miraculous chiral Ir‚ÄìRh bimetallic nanocatalyst for asymmetric hydrogenation of activated ketones
Authors: Xiuru Xue
Zhaohui Zhao
Yanhua Wang
Journal: Organic Chemistry Frontiers (2018)
Discipline: CHEMISTRY
Keywords: Chiral; Ir-Rh bimetallic nanocatalyst; Asymmetric hydrogenation; Activated ketones; Chiral secondary alcohols
Affiliations: State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, PR China

Abstract: A chiral Ir‚ÄìRh bimetallic nanocatalyst was synthesized and applied in the asymmetric hydrogenation of activated ketones to chiral secondary alcohols with up to >99% ee, even in a scale-up reaction. More importantly, the catalyst could be reused 6 times with no loss in catalytic performance and metal leaching. Remarkably, the effect of the molar ratio of Ir to Rh is very significant.

Retracted: Yes

PubPeer comments:
 Retraction of u2018A miraculous chiral Iru2013Rh bimetallic nanocatalyst for asymmetric hydrogenation of activated ketonesu2019 by Xiuru Xue et al., Org. Chem. Front., 2018, 5, 3585u20133589. We, the named authors, hereby wholly retract this Organic Chemistry Frontiers article due to concerns with the reliability of the NMR spectra in the published article. Upon repetition of the experiments, the authors found that the 1H-NMR spectra of compounds 1 and 2 provided in the published article were different in splitting pattern and or chemical shifts from their duplicated experiments. As the findings are unreliable, we are therefore retracting this article to maintain the accuracy of the scientific record. Signed: Xiuru Xue, Zhaohui Zhao and Yanhua Wang, 20th September 2019. Retraction endorsed by Wenjun Liu, Executive Editor, Organic Chemistry Frontiers. https: pubs.rsc.org en content articlehtml 2019 qo c9qo90089f ,
Hypertrophic cardiomyopathy mutations increase myofilament Ca2+ buffering, alter intracellular Ca2+ handling, and stimulate Ca2+-dependent signaling
Authors: Suketu Patel
Paul Robinson
Xing Liu
Barbara Casadei
Charles Redwood
Yin-Hua Zhang
Alexander Sparrow
Hugh Watkins
Journal: Journal of Biological Chemistry (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Ca2+/calmodulin-dependent protein kinase II (CaMKII); NFAT transcription factor; SERCA; cardiomyopathy; extracellular-signal-regulated kinase (ERK)
Affiliations: From the Cardiovascular Medicine Division, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom ., From the Cardiovascular Medicine Division, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, United Kingdom.

Abstract:  Mutations in thin filament regulatory proteins that cause hypertrophic cardiomyopathy (HCM) increase myofilament Ca2+ sensitivity. Mouse models exhibit increased Ca2+ buffering and arrhythmias, and we hypothesized that these changes are primary effects of the mutations (independent of compensatory changes) and that increased Ca2+ buffering and altered Ca2+ handling contribute to HCM pathogenesis via activation of Ca2+-dependent signaling. Here, we determined the primary effects of HCM mutations on intracellular Ca2+ handling and Ca2+-dependent signaling in a model system possessing Ca2+-handling mechanisms and contractile protein isoforms closely mirroring the human environment in the absence of potentially confounding remodeling. Using adenovirus, we expressed HCM-causing variants of human troponin-T, troponin-I, and Œ±-tropomyosin (R92Q, R145G, and D175N, respectively) in isolated guinea pig left ventricular cardiomyocytes. After 48 h, each variant had localized to the I-band and comprised ‚à?0% of the total protein. HCM mutations significantly lowered the Kd of Ca2+ binding, resulting in higher Ca2+ buffering of mutant cardiomyocytes. We observed increased diastolic [Ca2+] and slowed Ca2+ reuptake, coupled with a significant decrease in basal sarcomere length and slowed relaxation. HCM mutant cells had higher sodium/calcium exchanger activity, sarcoplasmic reticulum Ca2+ load, and sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) activity driven by Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of phospholamban. The ryanodine receptor (RyR) leak/load relationship was also increased, driven by CaMKII-mediated RyR phosphorylation. Altered Ca2+ homeostasis also increased signaling via both calcineurin/NFAT and extracellular signal-regulated kinase pathways. Altered myofilament Ca2+ buffering is the primary initiator of signaling cascades, indicating that directly targeting myofilament Ca2+ sensitivity provides an attractive therapeutic approach in HCM. 

Retracted: No

PubPeer comments:
 In Figure 1, panel B, there appears to be a vertical line between the R92Q and Control lanes. Can the authors provide the original Western blot image for this figure?  ,
K-ras-ERK1/2 down-regulates H2A.XY142ph through WSTF to promote the progress of gastric cancer
Authors: Jing Sun
Sha Ma
Guoying Zhang
Chao Dong
Journal: BMC Cancer (2019)
Discipline: CLINICAL MEDICINE
Keywords: Gastric cancer; H2A.XY142ph; Ras-ERK; WSTF, EYA3, MDM2.
Affiliations: Department of Clinical Medicine, Qujing Medical College, Qujing, 655000, Yunnan, China., Department of Pharmacy, Qujing Medical College, Sanjiang Avenue, Economic Development Zone, Qilin District, Qujing, 655000, Yunnan, China., Department of Pharmacy, Qujing Medical College, Sanjiang Avenue, Economic Development Zone, Qilin District, Qujing, 655000, Yunnan, China. .

Abstract:  Background: Histone H2AX phosphorylation at the site of Tyr-142 can participates in multiple biological progressions, which is including DNA repair. Ras pathway is closely involved in human cancers. Our study investigated the effects of Ras pathway via regulating H2AX.Y142ph. Methods: Gastric cancer cell line SNU-16 and MKN1 cells were transfected with Ras for G12D and T35S site mutation. The phosphorylation of H2A.XY142 and ERK1/2, WSTF and MDM2 was detected by western blot. Cell viability, cell colonies and migration was analyzed by MTT assay, soft-agar colony formation assay, and Transwell assay, respectively. The expression of Ras pathway related downstream factors, EYA3 and WSTF was detected by qRT-PCR. The relationship between Ras and downstream factors were detected by ChIP. The cell cycle progression was measured by flow cytometry. Results: RasG12D/T35V transection decreased the phosphorylation of H2A.XY142 and activated phosphorylation of ERK-1/2. H2A.XY142 inhibited cell viability, colonies and migration. H2A.XY142ph altered the expression of Ras downstream factors. CHIP assay revealed that RasG12D/T35V could bind to the promoters of these Ras pathway downstream factors. Silence of EYA3 increased H2A.XY142ph and inhibited cell viability, migration and percent cells in S stage. Furthermore, silence of EYA3 also changed the downstream factors expression. WSTF and H2A.XY142ph revealed the similar trend and MDM2 on the opposite. Conclusion: Ras/ERK signal pathway decreased H2A.XY142ph and promoted cell growth and metastasis. This Ras regulation process was down-regulated by the cascade of MDM2-WSTF-EYA3 to decrease H2A.XY142ph in SNU-16 cells. 

Retracted: No

PubPeer comments:
 Figure 7. * Red boxes: Lanes 1-3 in the p-ERK blot look similar to lanes 3-4 in the t-ERK blot. * Blue boxes: Lane 5 in the p-ERK blot looks similar to lane 6 in the t-ERK blot.  These concerns were reported to the journal in 2014, but the journal did not respond. ,
Long non-coding RNA PVT1 promotes cell proliferation and invasion through regulating miR-133a in ovarian cancer
Authors: Qi Yang
Yang Yu
Yuan Pan
Ziqian Sun
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Invasion; LncRNA; PVT1; Proliferation; miR-133a.
Affiliations: Department of Gynecology and Obstetrics, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, PR China., Center for Reproductive Medicine and Center for Prenatal Diagnosis, the First Hospital, Jilin University,71 Xinmin Street,Changchun, Jilin Province 130021, PR China., Center for Reproductive Medicine and Center for Prenatal Diagnosis, the First Hospital, Jilin University,71 Xinmin Street,Changchun, Jilin Province 130021, PR China. Electronic address: .

Abstract:  The long non-coding RNA, plasmacytoma variant translocation 1 (PVT1), was reportedly to be highly expressed in a variety of tumors including ovarian cancer (OC). However, the role and mechanism of action of PVT1 in the carcinogenesis and progression of OC remains largely unknown. PVT1 and miR-133a expression were detected by quantitative real time PCR(qRT-PCR) assays in OC tissues and cell lines. Cell Counting Kit-8 (CCK-8), flow cytometer, wound healing and transwell invasion assays were performed to evaluate cell proliferation, cycle, migration and invasion abilities, respectively. qRT-PCR and luciferase reporter assays demonstrated PVT1 regulated miR-133a expression. Here, we discovered that PVT1 shows higher expression in OC tissues than in normal ovarian tissues, and patients who show higher expression of PVT1 have worse progression-free and overall survivals compared to lower expression of PVT1. Additionally, we observed that knockdown of PVT1 significantly inhibited OC cell proliferation, and decreased the migration and invasion capabilities of OC cells. Mechanistically, miR-133a was identified to serve as a direct downstream target of PVT1 in OC. Knockdown of PVT1 inhibited cell proliferation, migration and invasion through negative regulating miR-133a in OC cells. Taken together, our finding shows that PVT1 may be a novel biomarker for prognosis and a promising therapeutic target for OC. 

Retracted: No

PubPeer comments:
 *[left]* Fig 2C from [**Yang et al (2018)**] .  Flow cytometry analysis of cell cycle arrest in SKOV3 cells transfected with si-PVT1 or si-Ctrl . *[middle]* Fig 2D from [Xu et al (2016)] .  Cell cycle arrest was determined in MCF7 cells transfected with miR-154 mimic or miR-Ctrl by flow cytometer assay . *[right]* Fig 2C from [Liu et al (2017)] . Cell  cycle distribution ... determined in TPC-1 cells transfected with miR-363 mimic or miR-NC.  Could the authors of any of these papers comment on the appearance of the same flow-cytometry histograms in all three of them? UPDATE: Another sighting! Fic 2C from [Liu, Wang Liu (2019)] .  ,
FGF21 contributes to neuroendocrine control of female reproduction
Authors: Bryn M Owen
Angie L Bookout
Steven A Kliewer
Laurent Gautron
Xunshan Ding
Stan D Atkin
David J Mangelsdorf
Vicky Y Lin
Journal: Nature medicine (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: reproduction; nutritional deprivation; adaptive process; mammals; fibroblast growth factor 21 (FGF21)
Affiliations: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Abstract:  Preventing reproduction during nutritional deprivation is an adaptive process that is conserved and essential for the survival of species. In mammals, the mechanisms that inhibit fertility during starvation are complex and incompletely understood. Here we show that exposure of female mice to fibroblast growth factor 21 (FGF21), a fasting-induced hepatokine, mimics infertility secondary to starvation. Mechanistically, FGF21 acts on the suprachiasmatic nucleus (SCN) in the hypothalamus to suppress the vasopressin-kisspeptin signaling cascade, thereby inhibiting the proestrus surge in luteinizing hormone. Mice lacking the FGF21 co-receptor, Œ≤-Klotho, in the SCN are refractory to the inhibitory effect of FGF21 on female fertility. Thus, FGF21 defines an important liver-neuroendocrine axis that modulates female reproduction in response to nutritional challenge. 

Retracted: No

PubPeer comments:
 Please when reading this article keep in mind a more recent paper published in Mol. Metab. (Singhal et al., 2016; doi: 10.1016 j.molmet.2016.05.010)  We confirmed that FGF21-Tg mice consuming a chow diet are indeed infertile. **In contrast to this finding, we observed that female mice consuming a ketogenic diet (KD), a model with dramatic increases in hepatic synthesis of FGF21 and elevated serum levels, demonstrate normal estrus cycles and remain fertile**. Further infusion of FGF21 into the lateral ventricle had no effect on fertility in wild type (WT) female mice. and  FGF21-Tg mice express supraphysiologic levels of FGF21, and females are infertile as reported previously [13] and also as observed by us. However, high FGF21 levels may not necessarily be associated with infertility as female WT mice consuming KD for as long as three months maintain normal cycling and can become pregnant despite the multi-fold rise in serum FGF21. Furthermore, if high FGF21 levels serve as a nutritional signal to suppress fertility in states of relative caloric insufficiency, mice lacking FGF21 should demonstrate either earlier puberty or attenuated suppression of cycling after fasting, a phenomenon which we did not observe. Finally, direct infusion of FGF21 into the brain at doses known to induce peripheral browning failed to have any effects on the estrus cycle. ,
Two Metal‚ÄìOrganic Frameworks: Luminescent Detection Performance and Treatment Activity on Chronic Glomerulus Nephritis Mediated by E. coli Abundance Regulation
Authors: Wang, Hong-Ru
He, Hai-Dong
Tang, Yu-Yan
Xu, Xu-Dong
Huan, Hong-Mei
Journal: Journal of Cluster Science (2021)
Discipline: CHEMISTRY
Keywords: Metal-organic frameworks; Eu(III); Cu2+; fluorescent intensity; quenching constant

Abstract: Two new metal‚Äìorganic frameworks (MOFs) [Eu(Hpta)(C2O4)]¬∑3H2O (1) and {[Co(pta)]¬∑1.5H2O}n (2) were prepared via reaction of the corresponding metal salts with a bifunctional organic ligand 2-(4-pyridyl)-terephthalic acid (H2pta) under the solvothermal reaction conditions. The Eu(III)-based complex 1 is highly selective and sensitive to Cu2+ in the water solution, and nearly 93% of its fluorescent intensity could be quenched when the Cu2+ ion concentration is 10‚Ä?&nbsp;mol/L. Complex 1 has a relative high quenching constant KSV of 1163&nbsp;M\u22121,which might be highly related to its uncoordinated nitrogen sites for the binding with Cu2+ ion in aqueous solution as reflected by the X-ray photoelectron spectroscopy (XPS) analysis (from 399.6&nbsp;eV to 400.2&nbsp;eV). Furthermore, they were used for the chronic glomerulus nephritis treatment, the biological activity and detail mechanism was investigated. The CFU assay was implemented to determine the fecal bacterial numbers of Escherichia coli (E. coli) after treated with compound 1 or 2. Afterward, the western blot was implemented to determine the autophagic levels in the renal tubular endothelial cells.

Retracted: No

PubPeer comments:
 Another paper in an *oeuvre* of  Floor-wax-AND-a-dessert-topping papers, this time with glomerulus nephritis treatment as the dessert topping. As is customary in this *oeuvre*,  MOF is used in a broad sense, and includes inorganic catalysts and coatings.  Although many MOFs are assembled via a variety of methods, it is still challenging to control the structure of MOFs due to uncontrollable external elements such as temperature, pH value and solvent system, which have an important impact on the architecture of compounds, particularly the selection of organic ligands and metal ions [9u201313]. - [11]. D. Yuan, M. Sun, M. Zhao, S. Tang, J. Qi, X. Zhang, K. Wang, and B. Li (2020). Int. J. Electrochem. Sci. 15, 8761u20138770. ** Persulfate Promoted ZnIn2S4 Visible Light Photocatalytic Dye Decomposition ** - [12]. N. Jiang, Y. Liu, X. N. Yu, H. B. Zhang, and M. M. Wang (2020). Int. J. Electrochem. Sci. 15, 5520u20135528. ** Corrosion Resistance of Nickel-Phosphorus Nano-ZnO Composite Multilayer Coating Electrodeposited on Carbon Steel in Acidic Chloride Environments  **  The ligands composed of pyridine ring and carboxylic acid group have more coordination patterns to metal clusters or metal ions, which will lead to the diversity and complexity of MOFs structure [14u201319]. - [16]. C. Duan, Z. Su, Y. Cao, L. Hu, D. Fu, J. Ma, and Y. Zhang (2021). J. Clean. Prod. 283, 124635 ** Synthesis of core-shell u03b1-AlH3@Al(OH)3 nanocomposite with improved low-temperature dehydriding properties by mechanochemical mixing and ionic liquid treatment ** ,
Tumor-associated galectin-3 modulates the function of tumor-reactive T cells
Authors: Yoshihiro Miyahara
Weiyi Peng
Helen Y Wang
Guangyong Peng
Rong-Fu Wang
Journal: Cancer Research (2008)
Discipline: CLINICAL MEDICINE
Keywords: T cells; cancer immunosurveillance; tumor destruction; immune responses; antigen stimulation
Affiliations: The Center for Cell and Gene Therapy, Department of Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.

Abstract:  T cells play an important role in cancer immunosurveillance and tumor destruction. However, tumor cells alter immune responses by modulating immune cells through antigen stimulation and immunoregulatory cytokines. A better understanding of the interplay between tumor cells and T cells might provide new strategies to enhance antitumor immunity. Through an antigen-screening approach using colorectal tumor-reactive T cells, we identified an HLA-DR11-restricted T-cell epitope encoded by KIAA0040 as well as MHC-unrestricted human galectin-3 (Gal-3) expressed by tumor cells. Although the biological function of KIAA0040 remains to be determined, we found that Gal-3 functioned as an immune regulator for direct T-cell activation and function. T-cell activation induced by Gal-3 resulted in T-cell apoptosis. We showed that a high level of expression of Gal-3 promoted tumor growth in vitro and in vivo. Using a mouse tumor model, we showed that delivery of high doses of Gal-3 inhibited tumor-reactive T cells and promoted tumor growth in mice receiving tumor-reactive CD8(+) T cells. These findings suggest that Gal-3 may function as an immune regulator to inhibit T-cell immune responses and promote tumor growth, thus providing a new mechanism for tumor immune tolerance. 

Retracted: No

PubPeer comments:
 Seems like both Identical- Figure 5 and supplementary figure 3   ,
Cryptotanshinone Inhibites Bladder Cancer Cell Proliferation and Promotes Apoptosis via the PTEN/PI3K/AKT Pathway
Authors: Jiannan Liu
Yaodong Chen
Yadong Liu
Fanlu Lin
Yinshan Jin
Ruihua An
Rui Wang
Journal: Journal of Cancer (2020)
Discipline: CLINICAL MEDICINE
Keywords: PTEN/PI3K/AKT.; apoptosis; bladder cancer; cryptotanshinone; proliferation.

Abstract:  Cryptotanshinone (CTT), extracted from the root of Salvia miltiorrhiza Bunge (Danshen), exhibits activities against a variety of human cancers in vitro and in vivo. The purpose of this study was to investigate the potential inhibitory effect of CTT on bladder cancer. In this study, we found that CTT inhibited bladder cancer cell proliferation, migration, and invasion and promoted apoptosis. In addition, CTT modulated the expression of proteins via the PI3K/AKT pathway, and the inhibition of PI3K/AKT signalling was due to induction of PTEN expression. Taken together, the results of the present study demonstrated the anticancer effect of CTT on bladder cancer cells, which might be associated with the downregulation of PI3K/AKT/mTOR and NF-Œ∫B signalling pathway proteins, and this inhibition was mediated by the induction of PTEN. 

Retracted: No

PubPeer comments:
 Figure 2B is a chaotic collage of dots put together randomly. In Figure 3A, a micrograph has been duplicated and presented as something else.  ,
Studies on the inhibition of feline EGFR in squamous cell carcinoma: enhancement of radiosensitivity and rescue of resistance to small molecule inhibitors
Authors: Lisa Y Pang
David J Argyle
Rhona Muirhead
Donald A Yool
Gur√• T Bergkvist
Journal: Cancer Biology & Therapy (2011)
Discipline: CLINICAL MEDICINE
Keywords: EGFR targeting; feline squamous cell carcinoma; large animal model; receptor tyrosine kinase inhibitor; RNA interference
Affiliations: Royal (Dick) School of Veterinary Studies and The Roslin Institute, Division of Veterinary Clinical Sciences, The University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, UK. 

Abstract:  This study investigated different methods of EGFR (Epithelial Growth Factor Receptor) targeting in feline squamous cell carcinoma with the ultimate aim of establishing a large animal model of human head and neck cancer. Both small molecule receptor tyrosine kinase inhibitor (TKI) and RNA interference (RNAi) techniques were employed to target the feline EGFR. We demonstrated that the human drug gefitinib caused a reduction in cell proliferation and migration in a feline cell line. However, we also document the development of resistance that was not associated with mutation in the kinase domain. RNAi caused a potent reduction in EGFR activity and was able to overcome acquired gefitinib resistance. In addition, RNAi targeting of EGFR, but not gefitinib, caused an additive effect on cell killing when combined with radiation. These results support the use of feline SCC as a model of head and neck cancer in man in the search for novel and effective treatments for both tumors. 

Retracted: No

PubPeer comments:
 Figure 3. Much more similar than expected.  ,
Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats
Authors: Eman Ramadan
Salama A Salama
Marwa S Hamza
Journal: Scientific Reports (2021)
Discipline: Multidisciplinary
Keywords: Ulipristal acetate; UPA; uterine fibroids; pathologic progesterone receptor modulator-associated endometrial changes; PAECs
Affiliations: Clinical Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, P.O. Box 43, Cairo, 11837, Egypt. ., The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, P.O. Box 43, Cairo, 11837, Egypt., Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University Nasr City, Cairo, 11751, Egypt.

Abstract:  Ulipristal acetate (UPA) is effective in the treatment of uterine fibroids. However, its clinical use is hampered by the development of pathologic progesterone receptor modulator-associated endometrial changes (PAECs). The current study was designed to test the hypothesis that UPA-induced PAECs are associated with deranged expression of some metabolic genes. In addition, metformin can mitigate UPA-induced PAECs through modulating the expression of these genes. In the present study, twenty-eight female non-pregnant, nulligravid Wistar rats were treated with UPA (0.1 mg/kg/day, intragastric) and/or metformin (50 mg/kg/day, intragastric) for 8 weeks. Our results demonstrated that co-treatment with metformin significantly reduced UPA-induced PAECs. In addition, co-treatment with metformin and UPA was associated with significant increase in the Bax and significant reduction in Bcl-2, PCNA, Cyclin-D1and ER-Œ± as compared to treatment with UPA alone. Furthermore, treatment with UPA alone was associated with deranged expression of 3-phosphoglycerate dehydrogenase (3-PHGDH), glucose-6-phosphate dehydrogenase (G6PD), transketolase (TKT), fatty acid synthase (FAS) and CD36. Most importantly, co-treatment with metformin markedly reduced UPA-induced altered expression of these metabolic genes in endometrial tissues. In conclusion, UPA-induced PAECs are associated with altered expression of genes involved in cell proliferation, apoptosis, estrogen receptor, glucose metabolism and lipid metabolism. Co-treatment with metformin abrogated UPA-induced PAECs most likely through the modulation of the expression of these genes. 

Retracted: No

PubPeer comments:
 [Figure 3] looks exactly the same as [Figure 4] .  Figure 3  Figure 4 ,
Host switching of human lice to new world monkeys in South America
Authors: F√©lix Djossou
Laurent Abi-Rached
Didier Raoult
Stephen C Barker
Rezak Drali
Amina Boutellis
Journal: Infection Genetics and Evolution (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Amazonian head louse; Cospeciation; Host-switching; Pediculus mjobergi.
Affiliations: Aix Marseille Universit√©, URMITE, UM63, CNRS 7278, IRD 198, Inserm 1095, 13005 Marseille, France. Electronic address: ., Service de maladies Infectieuses et Tropicales, Centre Hospitalier de Cayenne, 97306 Cayenne Cedex, Guyane Fran√ßaise, France. Electronic address: ., Department of Parasitology, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia. Electronic address: .

Abstract:  The coevolution between a host and its obligate parasite is exemplified in the sucking lice that infest primates. In the context of close lice-host partnerships and cospeciation, Pediculus mjobergi, the louse of New World primates, has long been puzzling because its morphology resembles that of human lice. To investigate the possibility that P. mjobergi was transmitted to monkeys from the first humans who set foot on the American continent thousands of years ago, we obtained and compared P. mjobergi lice collected from howler monkeys from Argentina to human lice gathered from a remote and isolated village in Amazonia that has escaped globalization. Morphological examinations were first conducted and verified the similarity between the monkey and human lice. The molecular characterization of several nuclear and mitochondrial genetic markers in the two types of lice revealed that one of the P. mjobergi specimens had a unique haplotype that clustered with the haplotypes of Amazonian head lice that are prevalent in tropical regions in the Americas, a natural habitat of New World monkeys. Because this phylogenetic group forms a separate branch within the clade of lice from humans that were of American origin, this finding indicates that human lice have transferred to New World monkeys. 

Retracted: No

PubPeer comments:
  , 
  ,
AIB1 induces epithelial‚Äêmesenchymal transition in gastric cancer via the PI3K/AKT signaling
Authors: Wei Han
Qiao Mei
Yang Li
Jing Hu
Lei Diao
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AIB1; PI3K/AKT signaling; epithelial-mesenchymal transition; gastric cancer.
Affiliations: Department of GastroenterologyThe First Affiliated Hospital of Anhui Medical University Hefei China

Abstract:  Amplified in breast cancer 1 (AIB1) is overexpression in various cancers and promotes tumor cell proliferation, survival, and invasiveness. However, the role of AIB1 in the regulation of gastric cancer (GC) cell epithelial-mesenchymal transition (EMT) is still largely unclear. In the present study, immunohistochemistry showed that AIB1 was upregulated in our cohort of patients with GC and correlated with poor survival. Knockdown of AIB1 reduced the invasive ability of GC cells, downregulated the expression of epithelial cell marker E-cadherin, and upregulated mesenchymal cell marker vimentin. AIB1 overexpression elicited the opposite effect. PI-103, the inhibitor of the PI3K/AKT signaling, partially reversed AIB1 overexpression mediated a decrease in E-cadherin and an increase in vimentin. The present data demonstrated that AIB1 augmented the EMT via activation of PI3K/AKT signaling. In conclusion, our results suggested a novel role of AIB1 in GC invasion and EMT and raised the possibility of using this molecule as an indicator for GC treatment. 

Retracted: Yes

PubPeer comments:
 Figure 2C. * Red boxes: In the SGC7901 panels, the AIB1-siRNA-1 and -2 panels appear to show an overlap. * Blue boxes: In the BGC823 panels, the AIB1-siRNA-1 and -2 panels appear to look similar.  , 
 Figure 5A. * Green boxes: The SGC7901 Vector panel appears to show an overlap with the BGC823 Vector panel. * Brown boxes: The SGC7901 AIB1+PI-103 panel appears to show an overlap with the BGC823 AIB1+PI-103 panel.  , 
 Retracted [27 October 2021] . -------------------- The above article, published online on November 6, 2019 in Wiley Online Library has been retracted by agreement between the authors, the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed after the authors stated that unintentional errors occurred during the research process, and the experimental results cannot be verified. Thus, the conclusions are considered to be invalid. ,
Sorafenib augments cytotoxic effect of S-1 in vitro and in vivo through TS suppression
Authors: Keijiro Kiyoshima
Masaki Shiota
Akira Yokomizo
Katsunori Tatsugami
Junichi Inokuchi
Ario Takeuchi
Kentaro Kuroiwa
Seiji Naito
Masatoshi Eto
Journal: Cancer Chemotherapy and Pharmacology (2011)
Discipline: CLINICAL MEDICINE
Keywords: Sorafenib; S-1; renal cell carcinoma; combination therapy; molecular targeting agents
Affiliations: Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Abstract:  Purpose: Sorafenib, a multikinase and tyrosine-kinase inhibitor, has anti-tumor activity in patients with advanced renal cell carcinoma (RCC). Recently, we reported that S-1 was active and well tolerated for the treatment of cytokine-refractory metastatic RCC. Therefore, we hypothesized that S-1 might be a good candidate for combination therapy with molecular targeting agents. In this study, we examined the mechanisms underlying for the synergism between S-1 and Sorafenib for RCC treatment in vitro and in tumor-bearing murine models. Methods: Human RCC cell lines were used for the in vitro cell proliferation assay. ACHN and 786-O tumors were subcutaneously transplanted into NCr-nu/nu-mice. Mice were treated with S-1 and/or Sorafenib, and tumor growth and side effects were monitored. Results: Synergistic anti-proliferative effects of Sorafenib and S-1 were clearly demonstrated in ACHN and 786-O cell lines in vitro due to the suppression of TS and E2F-1 expression. In the NCr-nu/nu model, the synergistic anti-tumor effects of S-1 and Sorafenib were again clearly seen, indicating direct synergistic effects of each drug on tumor growth. Conclusions: Our results demonstrate the synergistic activity of S-1 and Sorafenib and provided the rationale for combination therapy with S-1 and Sorafenib for the treatment of patients with advanced RCC. 

Retracted: No

PubPeer comments:
 Figure 2. * Red boxes: The actin panels in A (ACHN cells) and B (786-O cells) appear to look similar Reported to the journal together with 28 other papers in the summer of 2015, with a friendly reminder in April 2017, but no answer. With the exception of one paper, the journal did not correct or retract a single paper from this set. Could the authors please clarify if the journal contacted them back in 2015?  ,
Gene inversion potentiates bacterial evolvability and virulence
Authors: Christopher N Merrikh
Houra Merrikh
Journal: Nature Communications (2018)
Discipline: Multidisciplinary
Keywords: bacterial genes; replication machinery; RNA polymerases; GC skew calculation; evolutionary inversion record
Affiliations: Department of Microbiology, University of Washington, Health Sciences Building J-209, Seattle, WA, 98195, USA., Department of Microbiology, University of Washington, Health Sciences Building J-209, Seattle, WA, 98195, USA. ., Department of Genome Sciences, University of Washington, Seattle, 98195, WA, USA. .

Abstract:  Most bacterial genes are encoded on the leading strand, co-orienting the movement of the replication machinery with RNA polymerases. This bias reduces the frequency of detrimental head-on collisions between the two machineries. The negative outcomes of these collisions should lead to selection against head-on alleles, maximizing genome co-orientation. Our findings challenge this model. Using the GC skew calculation, we reveal the evolutionary inversion record of all chromosomally encoded genes in multiple divergent bacterial pathogens. Against expectations, we find that a large number of co-oriented genes have inverted to the head-on orientation, presumably increasing the frequency of head-on replication-transcription conflicts. Furthermore, we find that head-on genes, (including key antibiotic resistance and virulence genes) have higher rates of non-synonymous mutations and are more frequently under positive selection (dN/dS &gt; 1). Based on these results, we propose that spontaneous gene inversions can increase the evolvability and pathogenic capacity of bacteria through head-on replication-transcription collisions. 

Retracted: No

PubPeer comments:
 A preprint was recently deposited in bioRxiv calling into question the conclusions of this article - No support for the adaptive hypothesis of lagging-strand encoding in bacterial genomes - https: www.biorxiv.org content 10.1101 2020.01.14.906818v1  In conclusion, our reanalysis of the empirical data of Merrikh and Merrikh found no evidence for the adaptive hypothesis of lagging-strand encoding in bacterial genomes. Instead, all available data collected thus far are broadly consistent with the mutation-selection balance hypothesis ,