bluuebunny/crossref_metadata_2025_split huggingface dataset:
capCLIP: a new tool to probe protein synthesis in human cells through capture and identification of the eIF4E-mRNA interactome
Authors: Jensen Kirk B. , Dredge B. Kate , Toubia John , Jin Xin , Iadevaia Valentina , Goodall Gregory J. , Proud Christopher G. 
Published: April 2020

SummaryTranslation of eukaryotic mRNAs starts with binding of the m7G cap to the protein eIF4E followed by recruitment of other translation initiation factors. eIF4E’s essential role in translation suggests the cellular eIF4E-mRNA interactome (or ‘eIF4E cap-ome’) may serve as a faithful proxy of cellular translational activity. Here we describe capCLIP, a novel method to systematically capture and quantify the eIF4E cap-ome. To validate capCLIP, we identified the cap-omes in human cells ± the partial mTORC1 inhibitor rapamycin. As expected, TOP (terminal oligopyrimidine) mRNA representation is systematically reduced in rapamycin-treated cells. capCLIP tag data permits refinement of a 7-nucleotide TOP motif (5′-CUYUYYC-3′). We also apply capCLIP to probe the consequences of phosphorylation of eIF4E, whose function had remained unclear. eIF4E phosphorylation drives an overall reduction in eIF4E-mRNA association; strikingly, mRNAs most sensitive to phosphorylation possess short 5′-UTRs. capCLIP provides a sensitive and comprehensive measure of cellular translational activity. We foresee its application as a high-throughput way to assess translation in contexts not amenable to existing methodologies.
Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder
Authors: Mariano Livia Lacerda , Rousseau Matthieu , Varet Hugo , Legendre Rachel , Gentek Rebecca , Saenz Coronilla Javier , Bajenoff Marc , Perdiguero Elisa Gomez , Ingersoll Molly A 
Published: April 2020

SummaryResident macrophages are abundant in the bladder, playing key roles in immunity to uropathogens. Yet, whether they are heterogeneous, where they come from, and how they respond to infection remain largely unknown. We identified two macrophage subsets in mouse bladders, MacM in the muscle and MacL in the lamina propria, with distinct protein expression and transcriptomes. Using a urinary tract infection model, we validated our transcriptomic analyses, finding that MacM macrophages phagocytosed more bacteria and polarized to a more anti-inflammatory profile, whereas the MacL subset died rapidly during infection. During resolution, monocyte-derived cells contributed to tissue-resident macrophage pools and both subsets acquired transcriptional profiles distinct from naïve macrophages. Depletion of these altered macrophages resulted in the induction of a type 1 biased immune response to a second urinary tract infection, improving bacterial clearance. Our study uncovers the biology of resident macrophages and their response to an exceedingly common infection in a largely overlooked organ, the bladder.
Macrophage Function is Regulated by NPM1-mediated 2’-O-methylation
Authors: Sportoletti Paolo , Nachmani Daphna , Riccardi Luisa , Khanna-Gupta Arati , Chen Jian , Marra Andrea , Berliner Nancy , Clohessy John G. , Pandolfi Pier Paolo 
Published: April 2020

AbstractTheNPM1gene is frequently a target of genetic alteration in hematological tumors, particularly of the myeloid lineage. Complete inactivation ofNpm1in the mouse disrupts primitive hematopoiesis and results in embryonic lethality.Npm1heterozygosity produces features similar to those of MDS that progress to overt leukemia, and specific point mutations ofNpm1lead to bone marrow failure due to loss of hematopoietic stem cells. However, little is known about NPM1’s role in mature, differentiated cells. Here we generated a conditional mouse mutant to inactivateNpm1across the myelomonocytic lineage, and investigated its ability to influence macrophage maturation and function. We found thatNpm1is not required to maintain macrophage viability, while its loss in mature macrophages reduces production of reactive oxygen species, chemotactic properties and phagocytic capacity. Taking advantage of our recently establishedNpm1D180delmouse model of ribosome dysfunction and hematological disease, we identify cellular translation and rRNA 2’-O-methlyation as a crucial element in controlling macrophage function. These analyses demonstrate a role forNpm1in adult immune cells, and reveal the importance of translation regulation in macrophage function.Statement of significanceMacrophages are a major component of the immune response to various insults including to cancer. Here we show that NPM1, the most frequently mutated gene in acute myeloid leukemia, displays a critical role in macrophage function, and we identify ribosome deregulation as one of the underlying mechanisms.
Altered testicular cell type composition in males of two outbred mouse lines selected for high fertility
Authors: Michaelis Marten , Sobczak Alexander , Ludwig Carolin , Marvanová Hana , Langhammer Martina , Schön Jennifer , Weitzel Joachim M. 
Published: April 2020

AbstractBackgroundRecently we described two outbred mouse lines which have been selected for high fertility. These mouse models doubled the number of offspring per litter.ObjectivesAlthough selected for a primarily female‐trait of high fertility (increased litter size), we were interested whether also males of the fertility lines show differences within their reproductive organs.Materials and methodsWe investigated males from two outbred mouse lines which have been selected for the phenotype “high fertility” for more than 170 generations. In the present study, we analysed the testicular cell type composition by flow cytometry. We further investigated the weights of reproductive organs, histomorphometry of testis as well as studied sperm motility parameters using a thermal stress assay as well as a sperm hyperactivation assay.ResultsHere, we describe that males of the fertility line (FL) 1 show an increased percentage of diploid cells within the testis. Flow cytometric analysis identified this enlarged cell population as Leydig cells. Testis weights were unaffected whereas the weights of seminal vesicles of FL1 and FL2 were increased compared to Ctrl bucks. FL2 males show decreased diameter of tubulus seminiferi and an enhanced spermatid/Sertoli cell index. Sperm motility parameters of FL1 and Ctrl males are initially indistinguishable but FL1 spermatozoa show a better performance in a thermal stress experiment over a 5 hours observation period.DiscussionThese data indicate that although selected for a primarily female‐trait of high fertility also males from the fertility lines are effected by defined alterations in their reproductive organs.ConclusionSome of these alterations are FL1‐specific others are FL2‐associated, indicating that different molecular strategies warrant the high‐fertility phenotype on the female as well as on the male side.
Prolonged therapeutic effects of photoactivated adipose‐derived stem cells following ischaemic injury
Authors: Fan Xin , Li Kai , Zhu Luochen , Deng Xin , Feng Ziqian , Xu Chunrong , Liu Sijing , Wu Jianbo 
Published: April 2020

AbstractAimAdipose‐derived stem cells (ASCs) therapies are emerging as a promising approach to therapeutic angiogenesis. Therapeutic persistence and reduced primitive stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches.MethodsCultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Unilateral hindlimb ischaemia model was induced in high‐fat diet (HFD)‐fed mice by femoral artery interruption, after which photoactivated and non‐light‐treated ASCs were injected into the tail vein of mice. Laser Doppler imaging was conducted to measure the blood flow reperfusion. Capillary density was measured in the ischaemic gastrocnemius muscle. mRNA levels of angiogenic factors were determined by reverse‐transcription polymerase chain reaction. Flow cytometry was used to determine the characterization of ASCs and endothelial progenitor cell (EPC). Human ASCs secretomes were analysed by liquid chromatography tandem mass spectrometry.ResultsOur study demonstrated that photoactivated ND‐ASCs prolonged functional blood flow perfusion and increased ASCs‐derived EPC and neovascularization 38 days after ligation, when compared with saline‐treated controls. Profiling analysis in ischaemic muscles showed upregulation of genes associated with pro‐angiogenic factors after injection of photoactivated ND‐ASCs when compared with the non‐light‐treated ASCs or saline treated HFD mice. Mass spectrometry revealed that light‐treated ASCs conditioned medium retained a more complete pro‐angiogenic activity with significant upregulation of angiogenesis related proteins.ConclusionOur data demonstrates that photoactivated ND‐ASCs improve blood flow recovery and their injection may prove to be a useful strategy for the prevention and treatment of diabetic peripheral arterial disease.
Ensiling characteristics of total mixed ration prepared with local feed resources in Mozambique and their effects on nutrition value and milk production in Jersey dairy cattle
Authors: Du Zhumei , Yamasaki Seishi , Oya Tetsuji , Nguluve Damiao , Tinga Benedito , Macome Felicidade , Cai Yimin 
Published: April 2020

AbstractTo effectively utilize total mixed ration (TMR) prepared with locally available feed resources, we studied the nutritional value and milk production in Jersey dairy cattle fed a local general diet (LGD) and fermented TMR in Mozambique. Ten head of Jersey dairy cattle with 337 ± 19.8 kg body weight, aged 3–4 years in mid location were used in this study. The LGD diet was designed following the general feeding method of local smallholding farms; it contained native grass, Napier grass, wheat bran, and mineral–vitamin mix. Fermented TMR was prepared using Napier grass, corn bran, wheat bran, formula feed, and mineral–vitamin mix. Fermented TMR was preserved as good quality, with a relatively low pH and high lactic acid content. Compared to LGD, fermented TMR significantly improved the dry matter intake and digestibility in dairy cattle. Milk yield was significantly higher in dairy cattle fed with TMR than in those fed with LGD, by 3.75 L/d; milk quality was not significantly different between treatments. The results confirmed that LGD had a low dry matter intake and milk yield, and fermented TMR prepared with local feed resources can attain good quality and improve milk yield in dairy cattle in Mozambique.
Long‐term farming systems and last crop sown shape the species and functional composition of the arable weed seed bank
Authors: Rotchés‐Ribalta Roser , Sans Francesc Xavier , Mayer Jochen , Mäder Paul 
Published: April 2020

AbstractQuestions: The assembly of arable weed communities is the result of local filtering by agricultural management and crop competition. Therefore, soil seed banks can reflect the effects of long‐term cumulative field management and crop sequences on weed communities. Moreover, soil seed banks provide strong estimates of future weed problems but also of potential arable plant diversity and associated ecological functions. For this, we evaluated the effects of different long‐term farming systems under the same crop rotation sequence on the abundance, diversity and community assembly of weed seed bank, as well as on the functional diversity and composition.Location: DOK (biodynamic [D], bioorganic [O], conventional [K]) long‐term trial, Therwil, Switzerland.Methods: The effects of long‐term contrasted farming systems (i.e., biodynamic, organic, conventional, mineral and unfertilised systems) and last crop sown (i.e., wheat and maize) were evaluated on different indicators of species and functional diversity and composition of the weed soil seed bank.Results: The results showed significant influences of 40 years of contrasted farming systems on the diversity and composition of the seed bank, with higher diversities being found in unfertilised and organic farming systems, but also higher abundances than those found under conventional systems. Organic farming also allowed higher functional richness, dispersion and redundancy. Different farming systems triggered shifts in species and functional assemblies.Conclusions: The results highlight the importance of organic management for the maintenance of a diverse arable plant community and its functions. However, such results emphasise the need for appropriate yearly management to reduce the abundance of settled weediness and prevent affecting crop production. The farm management filtered community composition based on functional traits. Although the soil seed bank buffers the long‐term farming and crop sequence, the last crop sown and, thus, the yearly management were important determinants of seed bank composition.
I (dis)like the way you (dis)like them: The role of extended contact on social distance and attitudes towards the ingroup
Authors: Bagci Sabahat Cigdem , Stathi Sofia , Vezzali Loris , Turnuklu Abbas , Piyale Zeynep Ecem 
Published: April 2020

While extended intergroup contact has been commonly studied in the context of prejudice reduction, less is known about its implications for processes related to the ingroup. Through three correlational and one experimental studies (total N = 897) conducted in two different intergroup contexts (Turkey and United Kingdom), we investigated whether extended intergroup contact relates to social distance and attitudes towards ingroup members as a function of outgroup attitudes. We also investigated ingroup identification and perceived ingroup morality as potential mediators in these associations. Correlational studies demonstrated that especially when outgroup attitudes were more negative, participants’ positive (but not negative) extended contact was related to a more negative evaluation of the ingroup; whereas when outgroup attitudes were more positive, extended contact was associated with positive attitudes towards the ingroup. We found experimental evidence for the suggested relationships in relation to ingroup social distance. Findings are discussed in the light of vicarious dissonance theory and deprovincialization hypothesis.
REV‐ERBα activates the mTOR signalling pathway and promotes myotubes differentiation
Authors: Dadon‐Freiberg Maayan , Chapnik Nava , Froy Oren 
Published: April 2020

Background InformationMammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a master regulator of cell and whole‐body energy homoeostasis. REV‐ERBα is a nuclear receptor that plays an important role in metabolism. While mTORC1 activation is necessary for muscle differentiation, the role of REV‐ERBα is less clear.ResultsWe studied the effect of REV‐ERBα overexpression and silencing as well as mTORC1 activation and inhibition on the differentiation of C2C12 myoblasts to myotubes. mTOR, myogenin and REV‐ERBα were induced during differentiation of myoblasts into myotubes. REV‐ERBα was found to activate mTORC1 during the differentiation process even in the absence of the differentiation medium. This activation was presumably through the downregulation of the expression of TSC1, an mTORC1 inhibitor.ConclusionHerein we show that REV‐ERBα promotes myoblasts differentiation via the activation of the mTORC1 signalling pathway.SignificanceREV‐ERBα modulation can activate mTORC1 signalling and promote myoblasts differentiation.
Tyrosine kinase inhibitors induce alternative spliced BCR‐ABLIns35bp variant via inhibition of RNA polymerase II on genomic BCR‐ABL
Authors: Yuda Junichiro , Odawara Jun , Minami Mariko , Muta Tsuyoshi , Kohno Kentaro , Tanimoto Kazuki , Eto Tetsuya , Shima Takahiro , Kikushige Yoshikane , Kato Koji , Takenaka Katsuto , Iwasaki Hiromi , Minami Yosuke , Ohkawa Yasuyuki , Akashi Koichi , Miyamoto Toshihiro 
Published: April 2020

AbstractTo elucidate dynamic changes in native BCR‐ABL and alternatively spliced tyrosine kinase inhibitor (TKI)‐resistant but function‐dead BCR‐ABLIns35bp variant, following commencement or discontinuation of TKI therapy, each transcript was serially quantified in patients with chronic myeloid leukemia (CML) by deep sequencing. Because both transcripts were amplified together using conventional PCR system for measuring International Scale (IS), deep sequencing method was used for quantifying such BCR‐ABL variants. At the initial diagnosis, 7 of 9 patients presented a small fraction of cells possessing BCR‐ABLIns35bp, accounting for 0.8% of the total IS BCR‐ABL, corresponding to actual BCR‐ABLIns35bp value of 1.1539% IS. TKI rapidly decreased native BCR‐ABL but not BCR‐ABLIns35bp, leading to the initial increase in the proportion of BCR‐ABLIns35bp. Thereafter, both native BCR‐ABL and BCR‐ABLIns35bp gradually decreased in the course of TKI treatment, whereas small populations positive for TKI‐resistant BCR‐ABLIns35bp continued fluctuating at low levels, possibly underestimating the molecular response (MR). Following TKI discontinuation, sequencing analysis of 54 patients revealed a rapid relapse, apparently derived from native BCR‐ABL+ clones. However, IS fluctuating at low levels around MR4.0 marked a predominant persistence of cells expressing function‐dead BCR‐ABLIns35bp, suggesting that TKI resumption was unnecessary. We clarified the possible mechanism underlying mis‐splicing BCR‐ABLIns35bp, occurring at the particular pseudo‐splice site within intron8, which can be augmented by TKI treatment through inhibition of RNA polymerase II phosphorylation. No mutations were found in spliceosomal genes. Therefore, monitoring IS functional BCR‐ABL extracting BCR‐ABLIns35bp would lead us to a correct evaluation of MR status, thus determining the adequate therapeutic intervention.
Clinical and functional consequences of anti-properdin autoantibodies in patients with lupus nephritis
Authors: Radanova M , Mihaylova G , Ivanova D , Daugan M , Lazarov V , Roumenina L , Vasilev V 
Published: April 2020

SummaryProperdin is the only positive regulator of the complement system. In this study, we characterize the prevalence, functional consequences and disease associations of autoantibodies against properdin in a cohort of patients with autoimmune disease systemic lupus erythematosus (SLE) suffering from lupus nephritis (LN). We detected autoantibodies against properdin in plasma of 22·5% of the LN patients (16 of 71) by enzyme-linked immunosorbent assay (ELISA). The binding of these autoantibodies to properdin was dose-dependent and was validated by surface plasmon resonance. Higher levels of anti-properdin were related to high levels of anti-dsDNA and anti-nuclear antibodies and low concentrations of C3 and C4 in patients, and also with histological signs of LN activity and chronicity. The high negative predictive value (NPV) of anti-properdin and anti-dsDNA combination suggested that patients who are negative for both anti-properdin and anti-dsDNA will not have severe nephritis. Immunoglobulin G from anti-properdin-positive patients’ plasma increased the C3b deposition on late apoptotic cells by flow cytometry. Nevertheless, these IgGs did not modify substantially the binding of properdin to C3b, the C3 convertase C3bBb and the pro-convertase C3bB, evaluated by surface plasmon resonance. In conclusion, anti-properdin autoantibodies exist in LN patients. They have weak but relevant functional consequences, which could have pathological significance.
Endoscopic management of walled‐off pancreatic necrosis
Authors: Yasuda Ichiro , Takahashi Kosuke 
Published: April 2020

Walled‐off pancreatic necrosis (WON) can develop in the late phase of necrotizing pancreatitis. When the WON is accompanied by an infection in the necrotic bed, it becomes a life‐threatening complication. Open necrosectomy with drainage has been the standard treatment; however, it is associated with a significant morbidity and high mortality. Therefore, minimally invasive therapeutic alternatives are in demand. Recently, a new treatment algorithm for necrotizing pancreatitis, known as the step‐up approach, has been proposed. The initial report on it consisted of percutaneous drainage followed by, if necessary, a minimally invasive retroperitoneal necrosectomy. However, the endoscopic step‐up approach, which consists of EUS‐guided transluminal drainage followed by, if necessary, endoscopic necrosectomy, was later introduced. Recent studies have suggested that an endoscopic step‐up approach might be more advantageous than a minimally invasive surgical step‐up approach. A lumen apposing metal stent (LAMS) with a cautery‐enhanced delivery system is currently preferred over the conventional plastic stents for endoscopic interventions, because it decreases the technical difficulty of the procedure and may obviate the need for an adjunctive debridement procedure. However, some recent findings suggest that LAMS could be associated with a higher risk of stent‐related complications than conventional plastic stents, especially in patients with long‐term placement. Therefore, early removal of LAMS at 3 weeks post‐intervention is proposed if the WON is resolved on CT examination. Thus, endoscopic interventions have emerged as a key player in the management of WON. However, multidisciplinary treatment approaches should be considered because the endoscopic approach has limitations in treating complicated WON.
Prognosis of patients eligible for dapagliflozin in acute heart failure
Authors: Carballo Sebastian , Stirnemann Jérôme , Garin Nicolas , Darbellay Farhoumand Pauline , Serratrice Jacques , Carballo David 
Published: April 2020

AbstractBackgroundDapagliflozin, a sodium‐glucose cotransporter 2 inhibitor, was shown in the DAPA‐HF study to reduce the risk of worsening heart failure or death in symptomatic patients with left ejection fraction <40%, irrespective of diabetes. The aim of this study was to evaluate eligibility status for dapagliflozin in non‐selected patients hospitalized for acute decompensated heart failure (ADHF), as well as prognostic implications of this status.Materials and methodsAnalysis of 815 patients recruited in a prospective cohort of acute heart failure at the University Hospitals of Geneva, consisting of consecutive patients admitted with ADHF. Eligibility for dapagliflozin was determined using criteria described DAPA‐HF.ResultsOf 815 patients, 220 (27%) were eligible for dapagliflozin treatment. In survival analysis, patients who were eligible for dapagliflozin had better clinical outcomes with respect to all‐cause mortality and rehospitalization as compared to those who were not eligible. In multivariate analysis, the hazard ratio for all‐cause mortality or readmission in patients eligible for dapagliflozin was 0.82 (95% CI 0.68‐0.999, P = .049) as compared to the non‐eligible.ConclusionsUsing DAPA‐HF criteria, only 27% of non‐selected patients admitted for ADHF are theoretically eligible for dapagliflozin. This eligibility for dapagliflozin is associated with better outcomes. Further evaluation of the benefits of dapagliflozin in selected HF patients may be of interest. This may have implications for selection criteria in future randomized effectiveness studies.