bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antigen receptor-mediated depletion of FOXP3 in induced regulatory T-lymphocytes via PTPN2 and FOXO1
Authors: Bothur Evita , Raifer Hartmann , Haftmann Claudia , Stittrich Anna-Barbara , Brüstle Anne , Brenner Dirk , Bollig Nadine , Bieringer Maria , Kang Chol-Ho , Reinhard Katharina , Camara Bärbel , Huber Magdalena , Visekruna Alexander , Steinhoff Ulrich , Repenning Antje , Bauer Uta-Maria , Sexl Veronika , Radbruch Andreas , Sparwasser Tim , Mashreghi Mir-Farzin , Wah Mak Tak , Lohoff Michael 
Published: October 2015

AbstractRegulatory T-cells induced via IL-2 and TGFβ in vitro (iTreg) suppress immune cells and are potential therapeutics during autoimmunity. However, several reports described their re-differentiation into pathogenic cells in vivo and loss of their key functional transcription factor (TF) FOXP3 after T-cell antigen receptor (TCR)-signalling in vitro. Here, we show that TCR-activation antagonizes two necessary TFs for foxp3 gene transcription, which are themselves regulated by phosphorylation. Although the tyrosine phosphatase PTPN2 is induced to restrain IL-2-mediated phosphorylation of the TF STAT5, expression of the TF FOXO1 is downregulated and miR-182, a suppressor of FOXO1 expression, is upregulated. TGFβ counteracts the FOXP3-depleting TCR-signal by reassuring FOXO1 expression and by re-licensing STAT5 phosphorylation. Overexpressed phosphorylation-independent active versions of FOXO1 and STAT5 or knockdown of PTPN2 restores FOXP3 expression despite TCR-signal and absence of TGFβ. This study suggests novel targets for stabilisation and less dangerous application of iTreg during devastating inflammation.
Multiple origins of BBCC allopolyploid species in the rice genus (Oryza)
Authors: Zou Xin-Hui , Du Yu-Su , Tang Liang , Xu Xin-Wei , Doyle Jeff J. , Sang Tao , Ge Song 
Published: October 2015

AbstractIn the rice genus (Oryza), about one half of the species are allopolyploids. These species are not only important resources for rice breeding but also provide a unique opportunity for studying evolution of polyploid species. In the present study, we sequenced four biparentally inherited nuclear loci and three maternally inherited chloroplast fragments from all diploid and tetraploid species with the B- and C-genome types in this genus. We detected at least three independent origins of three BC-genome tetraploid species. Specifically, the diploid O. punctata (B-genome) and O. officinalis (C-genome) were the parental progenitors of O. minuta and O. malampuzhaensis with O. punctata being the maternal donors, whereas the diploid O. punctata and O. eichingeri (C-genome) were the progenitors of tetraploid O. punctata with O. punctata being the paternal donor. Our relaxed clock analyses suggest that all the BBCC species originated within the last one million years, which is coincident with the severe climate oscillations occurred during the last ice age, implying the potential impact of climate change on their formations and dispersals. In addition, our results support previous taxonomic arguments that the tetraploid O. punctata might be better treated as a separate species (O. schweinfurthiana).
High protective efficacy of rice bran against human rotavirus diarrhea via enhancing probiotic growth, gut barrier function and innate immunity
Authors: Yang Xingdong , Twitchell Erica , Li Guohua , Wen Ke , Weiss Mariah , Kocher Jacob , Lei Shaohua , Ramesh Ashwin , Ryan Elizabeth P. , Yuan Lijuan 
Published: October 2015

AbstractPreviously, we showed that rice bran (RB) was able to reduce human rotavirus (HRV) diarrhea in gnotobiotic pigs. Here, we investigated its effect on the growth of diarrhea-reducing probiotic Lactobacillus rhamnosus GG (LGG) and Escherichia coli Nissle (EcN) and the resulting effects on HRV diarrhea, gut epithelial health, permeability and innate immune responses during virulent HRV challenge. On 3, 5 and 7 days of age pigs were inoculated with 2 × 104 colony-forming-units LGG+EcN to initiate colonization. Daily RB supplementation (replacing 10% calorie intake) was started at 5 days of age and continued until euthanasia. A subset of pigs in each group was challenged orally with 105 focus-forming-units of virulent HRV at 33 days of age. RB completely prevented HRV diarrhea in LGG+EcN colonized pigs. RB significantly promoted the growth of both probiotic strains in the gut (~5 logs) and increased the body-weight-gain at 4–5 weeks of age compared to non-RB group. After HRV challenge, RB-fed pigs had significantly lower ileal mitotic index and villus width and significantly increased intestinal IFN-γ and total IgA levels compared to non-RB group. Therefore, RB plus LGG+EcN colonization may represent a highly effective therapeutic approach against HRV and potentially a variety of other diarrhea-inducing enteric pathogens.
The first two cell-fate decisions of preimplantation mouse embryo development are not functionally independent
Authors: Mihajlović Aleksandar I. , Thamodaran Vasanth , Bruce Alexander W. 
Published: October 2015

AbstractDuring mouse preimplantation embryo development, three distinct cell lineages are formed, represented by the differentiating trophectoderm (TE), primitive endoderm (PrE) and the pluripotent epiblast (EPI). Classically, lineage derivation has been presented as a two-step process whereby outer TE cells are first segregated from inner-cell mass (ICM), followed by ICM refinement into either the PrE or EPI. As ICM founders can be produced following the fourth or fifth cleavage divisions, their potential to equally contribute to EPI and PrE is contested. Thus, modelling the early sequestration of ICM founders from TE-differentiation after the fourth cleavage division, we examined ICM lineage contribution of varying sized cell clones unable to initiate TE-differentiation. Such TE-inhibited ICM cells do not equally contribute to EPI and PrE and are significantly biased to form EPI. This bias is not caused by enhanced expression of the EPI marker Nanog, nor correlated with reduced apical polarity but associated with reduced expression of PrE-related gene transcripts (Dab2 and Lrp2) and down-regulation of plasma membrane associated Fgfr2. Our results favour a unifying model were the three cell lineages are guided in an integrated, yet flexible, fate decision centred on relative exposure of founder cells to TE-differentiative cues.
Inhibition of Transforming Growth Factor-β Receptor signaling promotes culture expansion of undifferentiated human Endometrial Mesenchymal Stem/stromal Cells
Authors: Gurung Shanti , Werkmeister Jerome A. , Gargett Caroline E. 
Published: October 2015

AbstractHuman endometrial MSC (eMSC) are a novel source of MSC easily harvested from the highly regenerative uterine lining. We have developed protocols for eMSC isolation from single cell suspensions using magnetic bead-sorting using a perivascular marker antibody to SUSD2 and culture expansion in serum free medium (SFM). Similar to other MSC, eMSC spontaneously differentiate into fibroblasts during culture expansion decreasing their purity and efficacy. The aim of this study was to determine if A83-01, a TGF-β receptor inhibitor prevents eMSC differentiation in culture. SUSD2+ eMSC were cultured in SFM with bFGF/EGF in 5% O2/5% CO2. At passage 6, eMSC were incubated with or without A83-01 for 7 days, then analysed for MSC properties. A83-01 dose dependently promoted SUSD2+ eMSC proliferation and blocked apoptosis via the SMAD 2/3 pathway. Fewer A83-01 treated cells were autofluorescent or stained with β-galactosidase, indicating reduced senescence. A83-01-treated cells had higher cloning efficiency, differentiated into mesodermal lineages and expressed MSC phenotypic markers. These data suggest that A83-01 maintains SUSD2+ eMSC stemness, promoting proliferation by blocking senescence and apoptosis in late passage cultures through binding to TGF-β receptors. Small molecules such as A83-01 may enable the expansion of undifferentiated MSC for use in tissue engineering and cell-based therapies.
Unconjugated Bilirubin exerts Pro-Apoptotic Effect on Platelets via p38-MAPK activation
Authors: NaveenKumar Somanathapura K. , Thushara Ram M. , Sundaram Mahalingam S. , Hemshekhar Mahadevappa , Paul Manoj , Thirunavukkarasu Chinnasamy , Basappa  , Nagaraju Ganesh , Raghavan Sathees C. , Girish Kesturu S. , Kemparaju Kempaiah , Rangappa Kanchugarakoppal S. 
Published: October 2015

AbstractThrombocytopenia is one of the most frequently observed secondary complications in many pathological conditions including liver diseases, where hyperbilirubinemia is very common. The present study sought to find the cause of thrombocytopenia in unconjugated hyperbilirubinemic conditions. Unconjugated bilirubin (UCB), an end-product of heme catabolism, is known to have pro-oxidative and cytotoxic effects at high serum concentration. We investigated the molecular mechanism underlying the pro-apoptotic effect of UCB on human platelets in vitro and followed it up with studies in phenylhydrazine-induced hyperbilirubinemic rat model and hyperbilirubinemic human subjects. UCB is indeed found to significantly induce platelet apoptotic events including elevated endogenous reactive oxygen species generation, mitochondrial membrane depolarization, increased intracellular calcium levels, cardiolipin peroxidation and phosphatidylserine externalization (p < 0.001) as evident by FACS analysis. The immunoblots show the elevated levels of cytosolic cytochrome c and caspase activation in UCB-treated platelets. Further, UCB is found to induce mitochondrial ROS generation leading to p38 activation, followed by downstream activation of p53, ultimately resulting in altered expression of Bcl-2 and Bax proteins as evident from immunoblotting. All these parameters conclude that elevated unconjugated bilirubin causes thrombocytopenia by stimulating platelet apoptosis via mitochondrial ROS-induced p38 and p53 activation.
Design Principles of Inert Substrates for Exploiting Gold Clusters’ Intrinsic Catalytic Reactivity
Authors: Gao Wang , Ting Cui Ting , Fu Zhu Yong , Wen Zi , Zhao Ming , Chen Li Jian , Jiang Qing 
Published: October 2015

AbstractUltralow stability of gold clusters prohibits the understanding of their intrinsic reactivity (that is vital for revealing the origin of gold’s catalytic properties). Using density functional theory including many-body dispersion method, we aim to ascertain effective ways in exploiting gold clusters’ intrinsic reactivity on carbon nanotubes (CNTs). We find that the many body van der Waals interactions are essential for gold clusters’ reactivity on CNTs and even for O2 activation on these supported clusters. Furthermore, curvature and dopant of CNTs are found to qualitatively change the balance between physisorption and chemisorption for gold clusters on CNTs, determining the clusters’ morphology, charge states, stability and reactivity, which rationalize the experimental findings. Remarkably, N doped small curvature CNTs, which effectively stabilize gold clusters and retain their inherent geometric/electronic structures, can be promising candidates for exploiting gold clusters’ intrinsic reactivity.
An improved method for detecting circulating microRNAs with S-Poly(T) Plus real-time PCR
Authors: Niu Yanqin , Zhang Limin , Qiu Huiling , Wu Yike , Wang Zhiwei , Zai Yujia , Liu Lin , Qu Junle , Kang Kang , Gou Deming 
Published: October 2015

AbstractWe herein describe a simple, sensitive and specific method for analysis of circulating microRNAs (miRNA), termed S-Poly(T) Plus real-time PCR assay. This new method is based on our previously developed S-Poly(T) method, in which a unique S-Poly(T) primer is used during reverse-transcription to increase sensitivity and specificity. Further increased sensitivity and simplicity of S-Poly(T) Plus, in comparison with the S-Poly(T) method, were achieved by a single-step, multiple-stage reaction, where RNAs were polyadenylated and reverse-transcribed at the same time. The sensitivity of circulating miRNA detection was further improved by a modified method of total RNA isolation from serum/plasma, S/P miRsol, in which glycogen was used to increase the RNA yield. We validated our methods by quantifying miRNA expression profiles in the sera of the patients with pulmonary arterial hypertension associated with congenital heart disease. In conclusion, we developed a simple, sensitive and specific method for detecting circulating miRNAs that allows the measurement of 266 miRNAs from 100 μl of serum or plasma. This method presents a promising tool for basic miRNA research and clinical diagnosis of human diseases based on miRNA biomarkers.
Regulation of fear extinction versus other affective behaviors by discrete cortical scaffolding complexes associated with NR2B and PKA signaling
Authors: Corcoran K A , Leaderbrand K , Jovasevic V , Guedea A L , Kassam F , Radulovic J 
Published: October 2015

AbstractIn patients suffering from post-traumatic stress disorder (PTSD), fear evoked by trauma-related memories lasts long past the traumatic event and it is often complicated by general anxiety and depressed mood. This poses a treatment challenge, as drugs beneficial for some symptoms might exacerbate others. For example, in preclinical studies, antagonists of the NR2B subunit of N-methyl-d-aspartate receptors and activators of cAMP-dependent protein kinase (PKA) act as potent antidepressants and anxiolytics, but they block fear extinction. Using mice, we attempted to overcome this problem by interfering with individual NR2B and PKA signaling complexes organized by scaffolding proteins. We infused cell-permeable Tat peptides that displaced either NR2B from receptor for activated C kinase 1 (RACK1), or PKA from A-kinase anchor proteins (AKAPs) or microtubule-associated proteins (MAPs). The infusions were targeted to the retrosplenial cortex, an area involved in both fear extinction of remotely acquired memories and in mood regulation. Tat-RACK1 and Tat-AKAP enhanced fear extinction, all peptides reduced anxiety and none affected baseline depression-like behavior. However, disruption of PKA complexes distinctively interfered with the rapid antidepressant actions of the N-methyl-D-aspartate receptors antagonist MK-801 in that Tat-MAP2 blocked, whereas Tat-AKAP completely inverted the effect of MK-801 from antidepressant to depressant. These effects were unrelated to the MK-801-induced changes of brain-derived neurotrophic factor messenger RNA levels. Together, the findings suggest that NR2B–RACK1 complexes specifically contribute to fear extinction, and may provide a target for the treatment of PTSD. AKAP-PKA, on the other hand, appears to modulate fear extinction and antidepressant responses in opposite directions.
Peroxisome proliferator-activated receptor-α-mediated transcription of miR-301a and miR-454 and their host gene SKA2 regulates endothelin-1 and PAI-1 expression in sickle cell disease
Authors: Gonsalves Caryn S. , Li Chen , Malik Punam , Tahara Stanley M. , Kalra Vijay K. 
Published: October 2015

Endothelin-1 (ET-1) and plasminogen activator inhibitor-1 (PAI-1) play important roles in pulmonary hypertension (PH) in sickle cell disease (SCD). Our previous studies show higher levels of placenta growth factor (PlGF) in SCD correlate with increased plasma levels of ET-1, PAI-1, and other physiological markers of PH. PlGF-mediated ET-1 and PAI-1 expression occurs via activation of hypoxia-inducible factor-1α (HIF-1α). However, relatively little is understood regarding post-transcriptional regulation of PlGF-mediated expression of ET-1 and PAI-1. Herein, we show PlGF treatment of endothelial cells reduced levels of miR-301a and miR-454 from basal levels. In addition, both miRNAs targeted the 3′-UTRs of ET-1 and PAI-1 mRNAs. These results were corroborated in the mouse model of SCD [Berkeley sickle mice (BK-SS)] and in SCD subjects. Plasma levels of miR-454 in SCD subjects were significantly lower compared with unaffected controls, which correlated with higher plasma levels of both ET-1 and PAI-1. Moreover, lung tissues from BK-SS mice showed significantly reduced levels of pre-miR-301a and concomitantly higher levels of ET-1 and PAI-1. Furthermore, we show that miR-301a/miR-454 located in the spindle and kinetochore-associated protein-2 (SKA2) transcription unit was co-transcriptionally regulated by both HIF-1α and peroxisome proliferator-activated receptor-α (PPAR-α) as demonstrated by SKA2 promoter mutational analysis and ChIP. Finally we show that fenofibrate, a PPAR-α agonist, increased the expression of miR-301a/miR-454 and SKA2 in human microvascular endothelial cell line (HMEC) cells; the former were responsible for reduced expression of ET-1 and PAI-1. Our studies provide a potential therapeutic approach whereby fenofibrate-induced miR-301a/miR-454 expression can ameliorate PH and lung fibrosis by reduction in ET-1 and PAI-1 levels in SCD.
Design of compact dual‐mode dual‐band filtering power divider with high selectivity
Authors: Cai Chuantao , Wang Jianpeng , Deng Yijing , Li Jia‐Lin 
Published: October 2015

A new design method for a compact dual‐mode dual‐band filtering power divider is proposed. To achieve two transmission poles in both of the two passbands, the odd‐ and even‐mode resonant properties of the dual‐mode resonator are employed in the design. By symmetrically locating four dual‐mode resonators at both sides of the main transmission line and choosing the proper output topology, the introduced circuit can successfully realise the dual‐band power division and filtering selectivity property. Two resistors are utilised to achieve good in‐band isolation performance of the filtering power divider. For demonstration, a dual‐band filtering power divider with two passbands centred at 2.2 and 2.7 GHz was designed and measured. Simulated and measured results are provided which show a good agreement.
Fast and effective method of CMRR enhancement for multichannel integrated circuits dedicated to biomedical measurements
Authors: Kmon P. , Grybos P. , Zoladz M. , Lisicka A. 
Published: October 2015

The common mode rejection ratio (CMRR) strongly depends on matching and this effect is clearly visible in multichannel recording systems. Therefore, a method for improving the CMRR in multichannel recording integrated circuits (ICs) dedicated to biomedical experiments is reported. The method is based on balancing the amplifier's inputs using leakage currents. The proposed technique was verified in the 64 channel IC processed in CMOS 180 nm. The measurement results show that with use of the proposed balancing technique the CMRR is increased by more than 30 dB. Additionally, in comparison to conventional CMRR measurement methods, the proposed solution is attractive in three ways: its on‐chip implementation simplicity, fast operation, and it is especially suitable for modern nanometre processes.
Hermeneutics and genocide: giving voice to the unspoken
Authors: Kelley Shawn 
Published: October 2015

AbstractThe discipline of philosophical hermeneutics, which has played a crucial role in the discipline of New Testament studies, is haunted by the Holocaust. While there has been a great deal of Heidegger scholarship on the interface of Heidegger’s Nazi engagement and his thought, such scholarly focus has been lacking in the larger field of hermeneutics. Current hermeneutical theorists have not explored the various ways that hermeneutical theorists may be responding to the Holocaust. This paper seeks to rectify this scholarly lacuna by drawing attention to what is largely unspoken in hermeneutical theory. My argument examines one particularly important strain of hermeneutical thinking should be seen as a response to fascism and genocide: the critique of instrumental rationality. I look at three seminal sets of scholars: Heidegger, Gadamer and the Frankfurt School. The three sets of thinkers share remarkably similar views about the ills of modernity and a remarkably similar philosophical narrative on how these ills came about. In this grand narrative, current political or social problems are surface symptoms of a deeper spiritual crisis produced by the Enlightenment. The bulk of the paper consists of a reading of central elements of the thought of Heidegger, Gadamer and the Frankfurt School. This reading demonstrates that, for each, the critique of instrumental rationality represents their fundamental approach to confronting fascism and genocide. In the course of the analysis, I identify the limitations of this approach as both a ground for an ontological approach to interpretation and a theoretical response to the problems of fascism and genocide. If hermeneutics wishes to confront the Holocaust, then it needs to allow the Holocaust to become the explicit rather than implicit horizon and, thereby, to allow the emergence of a new set of questions that will produce a new turn in the hermeneutical dialogue. This paper is published as part of a thematic collection dedicated to radical theologies.
Structural analysis of nucleosomal barrier to transcription
Authors: Gaykalova Daria A. , Kulaeva Olga I. , Volokh Olesya , Shaytan Alexey K. , Hsieh Fu-Kai , Kirpichnikov Mikhail P. , Sokolova Olga S. , Studitsky Vasily M. 
Published: October 2015

Significance
On the majority of eukaryotic genes RNA polymerase II meets nucleosomes during transcription of every ∼200 bp of DNA. The key features of Pol II–nucleosome encounter are conserved from yeast to human, but the molecular mechanism of this process remains unknown. Our data suggest a mechanism of formation of the high nucleosomal barrier to Pol II that participates in regulation of transcript elongation in eukaryotes. The proposed mechanism explains the remarkable efficiency of nucleosome survival during transcription, important for maintenance of epigenetic and regulatory histone modifications. Similar mechanisms are likely used during various other DNA transactions, including DNA replication and ATP-dependent chromatin remodeling. Some factors involved in chromatin transcription (e.g., FACT and PARP) participate in cancer development/aging.
Cross-immunity between strains explains the dynamical pattern of paramyxoviruses
Authors: Bhattacharyya Samit , Gesteland Per H. , Korgenski Kent , Bjørnstad Ottar N. , Adler Frederick R. 
Published: October 2015

Significance
Pathogens that invoke an immune response immediately after infection can also provide partial cross-protection against other strains of the same or closely related pathogens. This cross-protection can shape the epidemiological dynamics of multistrain pathogens when an epidemic of one strain temporarily suppresses the transmission of another. Identifying these interactions from time series of epidemiological data is difficult, particularly when prevalence oscillates seasonally. We use long-term incidence data on Respiratory Syncytial Virus (RSV), three serotypes of Human Parainfluenza Virus (HPIV), and Human Metapneumovirus to study mathematical models of different mechanisms of pathogen interaction. Our results show a strong signal of cross-protection from RSV in controlling the timing and magnitude of HPIV outbreaks, and a stronger interaction with more closely related serotypes.