bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered lymphoid development in mice deficient for the mAF4 proto-oncogene
Authors: Isnard Patricia , Coré Nathalie , Naquet Philippe , Djabali Malek 
Published: October 2019

AbstractSome chromosomal translocations in acute leukemias involve the fusion of the trithorax-related protein Mll (also called HRX, All1, Htrx,) with a variety of heterologous proteins. In acute lymphoblastic leukemia associated with the t(4;11)(q21;q23) translocation, the4q21 gene that fuses with Mll is AF4. To gain insight into the potential role of AF4 in leukemogenesis and development, this gene was inactivated by homologous recombination in mice. As expected from the tissue distribution of the AF4 transcript, development of both B and T cells is affected in AF4 mutant mice. A severe reduction of the thymic double positive CD4/CD8 (CD4+/CD8+) population was observed; in addition most double- and single-positive cells expressed lower levels of CD4 and CD8 coreceptors. Most importantly, the reconstitution of the double-positive compartment by expansion of the double-negative cell compartment was severely impaired in these mutant mice. In the bone marrow pre-B and mature B-cell numbers are reduced. These results demonstrate that the function of the mAF4 gene is critical for normal lymphocyte development. This raises the possibility that the disruption of the normal AF4 gene or its association with Mll function by translocation may orient the oncogenic process toward the lymphoid lineage. This represents the first functional study using a knock-out strategy on one of the Mll partner genes in translocation-associated leukemias.
Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages
Authors: Faust Nicole , Varas Florencio , Kelly Louise M. , Heck Susanne , Graf Thomas 
Published: October 2019

AbstractPluripotent hematopoietic stem cells have been studied extensively, but the events that occur during their differentiation remain largely uncharted. To develop a system that allows the differentiation of cultured multipotent progenitors by time-lapse fluorescence microscopy, myelomonocytic cells were labeled with green fluorescent protein (GFP) in vivo. This was achieved by knocking the enhanced GFP (EGFP) gene into the murine lysozyme M (lys) locus and using a targeting vector, which contains a neomycin resistant (neo) gene flanked by LoxP sites and “splinked” ends, to increase the frequency of homologous recombination. Analysis of the blood and bone marrow of thelys-EGFP mice revealed that most myelomonocytic cells, especially mature neutrophil granulocytes, were fluorescence-positive, while cells from other lineages were not. Removal of the neogene through breeding of the mice with the Cre-deleter strain led to an increased fluorescence intensity. Mice with an inactivation of both copies of the lys gene developed normally and were fertile.
A novel endoproteolytic processing activity in mitochondria of erythroid cells and the role in heme synthesis
Authors: Dzikaite Vijole , Kanopka Arvydas , Brock Jeremy H. , Kazlauskas Arunas , Melefors Öjar 
Published: October 2019

AbstractThe erythroid isoform of aminolevulinate synthase (eALAS) protein is a major control point in erythroid heme synthesis and hemoglobin formation. Erythroid cells were extracted from mouse blood and bone marrow and metabolically labeled with 35S-methionine. This was followed by immunoprecipitation of eALAS protein products. The results show that the N-terminus of the expected full-length 59-kd form of the eALAS protein is truncated in bone marrow erythroid cells by approximately 7 kd. More differentiated erythroid cells in the peripheral blood exhibit very little of this protein truncation. Erythroid cells from the bone marrow were isolated using monoclonal antibody TER-119 and were shown to contain a unique endoprotease activity that could cleave the eALAS protein to the shorter form in vitro. With or without the mitochondrial signal sequence, the eALAS protein could serve as a substrate for the cleavage. This cleavage renders a functional eALAS protein and only removes a domain of unclear function, which has previously been reported to vary in size as a result of alternative RNA splicing. The protease activity was enriched from the membranes of mitochondria from bone marrow cells and was shown to be different from mitochondrial processing peptidase, medullasin, and other known proteases. Apart from the mitochondrial processing peptidase that cleaves the import signal sequence, this is the first description of a mitochondrially located site-specific processing protease activity.
Microchimerism in bone marrow–derived CD34+ cells of patients after liver transplantation
Authors: Nierhoff Dirk , Horvath Henrik Csaba , Mytilineos Joannis , Golling Markus , Bud Octavian , Klar Ernst , Opelz Gerhard , Voso Maria Teresa , Ho Anthony D. , Haas Rainer , Hohaus Stefan 
Published: October 2019

Abstract
Lymphoid and dendritic cells of donor origin can be detected in the recipient several years after a solid organ transplantation. This phenomenon is termed microchimerism and could play a role in the induction of tolerance. The fate of other hematopoietic cells transferred by liver transplantation, in particular of stem and progenitor cells, is unknown. For this reason, we studied peripheral blood and bone marrow samples of 12 patients who had received a liver transplant from an HLA-DR mismatched donor. Eight patients were long-term survivors between 2.8 and 10.1 years after allografting. CD34+ cells from bone marrow were highly enriched with the use of a 2-step method, and a nested polymerase chain reaction was applied to detect donor cells on the basis of allelic differences of the HLA-DRB1 gene. Rigorous controls with DRB1 specificities equal to the donor and host were included. In 5 of 8 long-term liver recipients, donor-specific CD34+ cells could be detected in bone marrow. Microchimerism in the CD34+ cell fraction did not correlate to the chimeric status in peripheral blood. In conclusion, our results demonstrate a frequent microchimerism among bone marrow–derived CD34+ cells after liver transplantation. The functional role of this phenomenon still needs to be defined.
Homozygous truncation of the fibrinogen Aα chain within the coiled coil causes congenital afibrinogenemia
Authors: Fellowes Andrew P. , Brennan Stephen O. , Holme Randi , Stormorken Helge , Brosstad Frank R. , George Peter M. 
Published: October 2019

AbstractThe molecular basis of a novel congenital afibrinogenemia has been determined. The proposita, the only affected member in a consanguineous Norwegian family, suffers from a moderate to severe bleeding disorder due to the total absence of any detectable fibrinogen. Dot blots of solubilized platelets revealed a small amount of γ chain but no A or Bβ chains, whereas no chains were detected in plasma dot blots. DNA sequencing of the A chain gene revealed a homozygous C→T transversion 557 nucleotides from the transcription initiation site. This nucleotide change predicts the nonsense mutation A 149 Arg (CGA)→stop (TGA). Early truncation of the A chain appears to result in defective assembly or secretion of fibrinogen, probably due to the removal of the C-terminal disulfide ring residues that are critically required for the formation of a stable 3-chained half molecule.
METTL3-mediated N6-methyladenosine modification is critical for epithelial-mesenchymal transition and metastasis of gastric cancer
Authors: Yue Ben , Song Chenlong , Yang Linxi , Cui Ran , Cheng Xingwang , Zhang Zizhen , Zhao Gang 
Published: October 2019

Abstract

Background
As one of the most frequent chemical modifications in eukaryotic mRNAs, N6-methyladenosine (m6A) modification exerts important effects on mRNA stability, splicing, and translation. Recently, the regulatory role of m6A in tumorigenesis has been increasingly recognized. However, dysregulation of m6A and its functions in tumor epithelial-mesenchymal transition (EMT) and metastasis remain obscure.

Methods
qRT-PCR and immunohistochemistry were used to evaluate the expression of methyltransferase-like 3 (METTL3) in gastric cancer (GC). The effects of METTL3 on GC metastasis were investigated through in vitro and in vivo assays. The mechanism of METTL3 action was explored through transcriptome-sequencing, m6A-sequencing, m6A methylated RNA immunoprecipitation quantitative reverse transcription polymerase chain reaction (MeRIP qRT-PCR), confocal immunofluorescent assay, luciferase reporter assay, co-immunoprecipitation, RNA immunoprecipitation and chromatin immunoprecipitation assay.

Results
Here, we show that METTL3, a major RNA N6-adenosine methyltransferase, was upregulated in GC. Clinically, elevated METTL3 level was predictive of poor prognosis. Functionally, we found that METTL3 was required for the EMT process in vitro and for metastasis in vivo. Mechanistically, we unveiled the METTL3-mediated m6A modification profile in GC cells for the first time and identified zinc finger MYM-type containing 1 (ZMYM1) as a bona fide m6A target of METTL3. The m6A modification of ZMYM1 mRNA by METTL3 enhanced its stability relying on the “reader” protein HuR (also known as ELAVL1) dependent pathway. In addition, ZMYM1 bound to and mediated the repression of E-cadherin promoter by recruiting the CtBP/LSD1/CoREST complex, thus facilitating the EMT program and metastasis.

Conclusions
Collectively, our findings indicate the critical role of m6A modification in GC and uncover METTL3/ZMYM1/E-cadherin signaling as a potential therapeutic target in anti-metastatic strategy against GC.
Transplantation of bone marrow derived macrophages reduces markers of neuropathology in an APP/PS1 mouse model
Authors: Costa-Marques Luís , Arnold Katrin , Pardon Marie-Christine , Leovsky Christiane , Swarbrick Samantha , Fabian Claire , Stolzing Alexandra 
Published: October 2019

Abstract

Background
We investigated early hallmarks of putative therapeutic effects following systemic transplantation of bone marrow derived macrophages (BM-M) in APP/PS1 transgenic mice.

Method
BM-M were transplanted into the tail vein and the animals analysed 1 month later.

Results
BM-M transplantation promoted the reduction of the amyloid beta [37-42] plaque number and size in the cortex and hippocampus of the treated mice, but no change in the more heavily modified pyroglutamate amyloid beta E3 plaques. The number of phenotypically ‘small’ microglia increased in the hippocampus. Astrocyte size decreased overall, indicating a reduction of activated astrocytes. Gene expression of interleukin 6 and 10, interferon-gamma, and prostaglandin E receptor 2 was significantly lower in the hippocampus, while interleukin 10 expression was elevated in the cortex of the treated mice.

Conclusions
BM-M systemically transplanted, promote a decrease in neuroinflammation and a limited reversion of amyloid pathology. This exploratory study may support the potential of BM-M or microglia-like cell therapy and further illuminates the mechanisms of action associated with such transplants.
Aquaglyceroporins but not orthodox aquaporins are involved in the cryotolerance of pig spermatozoa
Authors: Delgado-Bermúdez Ariadna , Llavanera Marc , Fernández-Bastit Leira , Recuero Sandra , Mateo-Otero Yentel , Bonet Sergi , Barranco Isabel , Fernández-Fuertes Beatriz , Yeste Marc 
Published: October 2019

AbstractBackgroundAquaporins (AQPs) are a family of transmembrane water channels that includes orthodox AQPs, aquaglyceroporins (GLPs) and superAQPs. AQP3, AQP7, AQP9 and AQP11 have been identified in boar sperm, and they are crucial for sperm maturation and osmoregulation. Water exchange is an important event in cryopreservation, which is the most efficient method for long-term storage of sperm. However, the freeze-thaw process leads to sperm damage and a loss of fertilizing potential. Assuming that the quality of frozen-thawed sperm partially depends on the regulation of osmolality variations during this process, AQPs might play a crucial role in boar semen freezability. In this context, the aim of this study was to unravel the functional relevance of the different groups of AQPs for boar sperm cryotolerance through three different inhibitors.ResultsInhibition of different groups of AQPs was found to have different effects on boar sperm cryotolerance. Whereas the use of 1,3-propanediol (PDO), an inhibitor of orthodox AQPs and GLPs, decreased total motility (P < 0.05), it increased post-thaw sperm viability, lowered membrane lipid disorder and increased mitochondrial membrane potential (MMP) (P < 0.05). When acetazolamide (AC) was used as an inhibitor of orthodox AQPs, the effects on post-thaw sperm quality were restricted to a mild increase in MMP in the presence of the intermediate concentration at 30 min post-thaw and an increase in superoxide levels (P < 0.05). Finally, the addition of phloretin (PHL), a GLP inhibitor, had detrimental effects on post-thaw total and progressive sperm motilities, viability and lipid membrane disorder (P < 0.05).ConclusionsThe effects of the different inhibitors suggest that GLPs rather than orthodox AQPs are relevant for boar sperm freezability. Moreover, the positive effect of PDO on sperm quality suggests a cryoprotective role for this molecule.
A Role for Oncostatin M in the Impairment of Glucose Homeostasis in Obesity
Authors: Piquer-Garcia Irene , Campderros Laura , Taxerås Siri D , Gavaldà-Navarro Aleix , Pardo Rosario , Vila María , Pellitero Silvia , Martínez Eva , Tarascó Jordi , Moreno Pau , Villarroya Joan , Cereijo Rubén , González Lorena , Reyes Marjorie , Rodriguez-Fernández Silvia , Vives-Pi Marta , Lerin Carles , Elks Carrie M , Stephens Jacqueline M , Puig-Domingo Manel , Villarroya Francesc , Villena Josep A , Sánchez-Infantes David 
Published: October 2019

AbstractContextOncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood.ObjectiveThe aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice.Design28 patients with severe obesity were included and stratified into two groups: (1) glucose levels &lt;100 mg/dL and (2) glucose levels &gt;100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects.ResultsOSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, homeostatic model assessment of insulin resistance, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice.ConclusionsOSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance.
ETIKA BERMEDIA SOSIAL DALAM MENYIKAPI PEMBERITAAN BOHONG (HOAX) PERSPEKTIF HADIS
Authors: Al-Ayyubi M. Zia 
Published: October 2019

This paper will discusses about the troubling phenomenathat occur in cyberspace, precisely on social media. The negative contents are found, both attacking groups, and individuals.The attack usually uses content in the form of provocation, slander, hate speech, hoaxes, appealing opinions that lead to defamation, etc. The problem above, if we examine its historicity in Islamic history, it turns out that this phenomena has been happening since the early days of Islam. Precisely, one of the prophet's wives, Siti Aisyah, who was accused of committing adultery with one of the war soldiers. Then the incident became the cause of the revelation bara’ah’s letter. Back then, the kind of news mentioned above was disseminated by transmission media. In the present, it is disseminated with social media which is even faster in its flow of transmission. So the term viral appears. The offer submitted in this paper is the attitude and ethics of every netizens in social media with a hadith approach. So that it can be finally in accordance with the with the portion and proportion in utilizing a social media. Keyword: Hermeneutics Hadis, Etics, Social Media, Hoax.
PENAFSIRAN SUFISTIK KH. SHALIH DARAT TERHADAP Q.S. AL-BAQARAH: 183
Authors: Abshor M. Ulil 
Published: October 2019

Sufi interpretation is an important part in expressing the meaning contained in the Qur’an, there is the meaning of outer and inner meaning. The meaning of outer is the outside of textual meaning that is the spiritual area. Sufi interpretation does not mean leaving the aspect of outer or aspects of language, but at the same time combing the inner aspect, this also happens in the book of Tafsir Fayd al-Rahman by KH. Shalih Darat. The intended orientation in Sufiinterpretation is more about overcoming mental problems that often forget the essence of essential life. The inner meaning will provide added value in matters of worship, especially in the interpretation of the letter (Q.S. al-Baqarah: 183). In interpreting the verse KH. Shalih Darat interprets the Isyari, so that the essential inner meaning is obtained to express the social dimensions that encourage the birth of empathy in the family, social, and among humans. So that the container in realizing superior social dimensions in the community needs to increase fasting both in terms of dhohir and in terms of the heart. The approach taken in this study uses a sufistic approach to the theory of Sufi Ishari and Isharah method (Devine Method). The results obtained from the interpretation of the verse parse about fasting there are four things, taqwa which manifests on the dimension of divinity and the human dimension of basyariah, manifests itself in the form of love between humans, disciplined life and tazqiyah al-Nafs.Keywords: Fasting, Tafsir Faidh al-Rahman, Sufistik Logic
Hypothetical bias and framing effect in the valuation of private consumer goods
Authors: Brzozowicz Magdalena 
Published: October 2019

Abstract
In a laboratory experiment, I examined two behavioural effects: hypothetical bias and the framing effect. I elicited willingness to pay (WTP) for a cosmetic product, and manipulated framing conditions (positive vs. negative attribute framing) and incentives to reveal the actual valuation (hypothetical vs. real). I demonstrated that hypothetical bias has a significant impact on WTP values; however, the framing effect has no effect on the valuation of the product. Similarly, I found no interaction between the two effects. This observation contributes to claims that hypothetical research methods lead to equally reliable data as those based on consequential choices.
Thermodynamics and Industrial Trial on Increasing the Carbon Content at the BOF Endpoint to Produce Ultra-Low Carbon IF Steel by BOF-RH-CSP Process
Authors: Jing Guo , Shu-Sen Cheng , Hanjie Guo 
Published: October 2019

Abstract
Thermodynamic analysis was performed to obtain the relation between the carbon content at the BOF endpoint and the dissolved oxygen content in liquid steel and the (FeO + MnO) content in the slag with the help of thermodynamic calculation software FactSage. It finds that both the [O] and (FeO + MnO) content increase with decreasing the carbon content at the BOF endpoint and the increasing rate is larger when the carbon content is lower. In addition, in the case of the higher temperature at the BOF endpoint the [O] in liquid steel increase and the (FeO + MnO) in the slag increase as well. The consumption of O2 for decarbonization at the BOF endpoint is much more than that in RH degasser since the majority of the blowing O2 at the BOF endpoint will produce FeO into the slag, thus it increase the metal loss and deteriorate the steel cleanness during the consequent refining process. As a result, the carbon content at the BOF endpoint should be properly increased within the RH decarbonization ability. At last, industrial trials were carried out and confirmed that total oxygen consumption decrease obviously and the (FeO + MnO) of final BOF slag decline as well with increasing carbon content at BOF endpoint from 0.042% to 0.081%. In addition, it almost does not slow down the RH process and the carbon content in final steel all met the demand of the ultra-low carbon steel. In addition, mechanical properties of IF steel with higher carbon content at the endpoint of BOF are almost all more superior to those of heat with lower carbon content at BOF endpoint.
Numerical Analysis of TB32 Crash Tests for 4-cable Guardrail Barrier System Installed on the Horizontal Convex Curves of Road
Authors: Wilde Krzysztof , Bruski Dawid , Budzyński Marcin , Burzyński Stanisław , Chróścielewski Jacek , Jamroz Kazimierz , Pachocki Łukasz , Witkowski Wojciech 
Published: October 2019

Abstract
Horizontal curves are one of the elements of road infrastructure where statistically a relatively high number of accidents have been reported. In the last 10 years in Poland, approximately 10% of all road accidents happened on horizontal curves of roads and was responsible for approximately 14% of all fatalities on Polish roads. Thus, this issue is important and requires extensive research and proper road safety treatments. One possible measure that may contribute to improvement of safety on road curves may be barriers. The purpose of this work is to assess, with use of numerical simulations, the performance of the 4-cable barrier systems installed on horizontal road convex curves. The most important parameters for road safety barriers are presented including the effect of various impact velocities and the radiuses of the road curves.
Nonlinear Vibration of Truncated Conical Shells: Donnell, Sanders and Nemeth Theories
Authors: Bakhtiari Mehrdad , Lakis Aouni A. , Kerboua Youcef 
Published: October 2019

AbstractNonlinear free vibration of truncated conical shells has been investigated for three different shell theories; Donnell, Sanders and Nemeth to investigate the effect of their simplifying assumptions. The displacement field of a finite element model that was obtained from the exact solution of equilibrium equations of Sander’s improved first-approximation theory is used to define the nonlinear strain energy of conical shells. Employing generalized coordinates method the equations of motion are derived and subsequently the amplitude equation of nonlinear vibration of conical shells was developed. The amplitude equation is solved for multiple cases of isotropic materials. Linear and nonlinear free vibration results are validated against the existing studies in scientific literature and demonstrate good accordance. The validated model is used to investigate effects of different parameters including circumferential mode number, cone-half angle, length to radius ratio, thickness to radius ratio and boundary conditions for the nonlinear vibration of conical shells.
The crystal structure of 3-benzyl-1-((8-(benzyloxy)quinolin-2-yl)methyl)-1H-imidazol-3-ium hexafluorophosphate, C27H24N3OF6P
Authors: Jiewei Luo , Shilu Zhang , Yiming Liu , Bo Zhao 
Published: October 2019

Abstract
C27H24N3OF6P, monoclinic, Cc (no. 9), a = 18.0589(18) Å, b = 12.5100(9) Å, c = 13.3659(12) Å, β = 124.522(7)°, V = 2487.9(4) Å3, Z = 4, R
gt(F) = 0.0437, wR
ref(F
2) = 0.1141, T = 113(2) K.
Crystal structure of N′2
,N′6
-bis((E)-1-(pyrazin-2-yl)ethylidene)pyridine-2,6-dicarbohydrazide — methanol (1/2), C21H25N9O4
Authors: Xiangqing Fang , Ren Wang , Kai Du , Jia Gu , Liguo Yang 
Published: October 2019

Abstract
C21H25N9O4, monoclinic, P2/n (no. 13), a = 10.277(3) Å, b = 10.081(3) Å, c = 11.264(4) Å, β = 104.582(4)°, V = 1129.4(6) Å3, Z = 2, R
gt(F) = 0.0452, wR
ref(F
2) = 0.1278, T = 296(2) K [1], [2], [3].