bluuebunny/crossref_metadata_2025_split huggingface dataset:
miRNA profiling during antigen-dependent T cell activation: A role for miR-132-3p
Authors: Gutiérrez-Vázquez Cristina , Rodríguez-Galán Ana , Fernández-Alfara Marcos , Mittelbrunn María , Sánchez-Cabo Fátima , Martínez-Herrera Dannys Jorge , Ramírez-Huesca Marta , Pascual-Montano Alberto , Sánchez-Madrid Francisco 
Published: June 2017

AbstractmicroRNAs (miRNAs) are tightly regulated during T lymphocyte activation to enable the establishment of precise immune responses. Here, we analyzed the changes of the miRNA profiles of T cells in response to activation by cognate interaction with dendritic cells. We also studied mRNA targets common to miRNAs regulated in T cell activation. pik3r1 gene, which encodes the regulatory subunits of PI3K p50, p55 and p85, was identified as target of miRNAs upregulated after T cell activation. Using 3′UTR luciferase reporter-based and biochemical assays, we showed the inhibitory relationship between miR-132-3p upregulation and expression of the pik3r1 gene. Our results indicate that specific miRNAs whose expression is modulated during T cell activation might regulate PI3K signaling in T cells.
Human myogenic reserve cells are quiescent stem cells that contribute to muscle regeneration after intramuscular transplantation in immunodeficient mice
Authors: Laumonier Thomas , Bermont Flavien , Hoffmeyer Pierre , Kindler Vincent , Menetrey Jacques 
Published: June 2017

AbstractSatellite cells, localized within muscles in vivo, are Pax7+ muscle stem cells supporting skeletal muscle growth and regeneration. Unfortunately, their amplification in vitro, required for their therapeutic use, is associated with reduced regenerative potential. In the present study, we investigated if human myogenic reserve cells (MRC) obtained in vitro, represented a reliable cell source for muscle repair. For this purpose, primary human myoblasts were freshly isolated and expanded. After 2 days of differentiation, 62 ± 2.9% of the nuclei were localized in myotubes and 38 ± 2.9% in the mononucleated non-fusing MRC. Eighty percent of freshly isolated human MRC expressed a phenotype similar to human quiescent satellite cells (CD56+/Pax7+/MyoD−/Ki67− cells). Fourteen days and 21 days after cell transplantation in immunodeficient mice, live human cells were significantly more numerous and the percentage of Pax7+/human lamin A/C+ cells was 2 fold higher in muscles of animals injected with MRC compared to those injected with human myoblasts, despite that percentage of spectrin+ and lamin A/C+ human fibers in both groups MRC were similar. Taken together, these data provide evidence that MRC generated in vitro represent a promising source of cells for improving regeneration of injured skeletal muscles.
The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription
Authors: Rodríguez-Gil Alfonso , Ritter Olesja , Saul Vera V. , Wilhelm Jochen , Yang Chen-Yuan , Grosschedl Rudolf , Imai Yumiko , Kuba Keiji , Kracht Michael , Schmitz M. Lienhard 
Published: June 2017

AbstractThe multi-subunit CCR4 (carbon catabolite repressor 4)-NOT (Negative on TATA) complex serves as a central coordinator of all different steps of eukaryotic gene expression. Here we performed a systematic and comparative analysis of cells where the CCR4-NOT subunits CNOT1, CNOT2 or CNOT3 were individually downregulated using doxycycline-inducible shRNAs. Microarray experiments showed that downregulation of either CNOT subunit resulted in elevated expression of major histocompatibility complex class II (MHC II) genes which are found in a gene cluster on chromosome 6. Increased expression of MHC II genes after knock-down or knock-out of either CNOT subunit was seen in a variety of cell systems and also in naïve macrophages from CNOT3 conditional knock-out mice. CNOT2-mediated repression of MHC II genes occurred also in the absence of the master regulator class II transactivator (CIITA) and did not cause detectable changes of the chromatin structure at the chromosomal MHC II locus. CNOT2 downregulation resulted in an increasedde novotranscription of mRNAs whereas tethering of CNOT2 to a regulatory region governing MHC II expression resulted in diminished transcription. These results expand the known repertoire of CCR4-NOT members for immune regulation and identify CNOT proteins as a novel group of corepressors restricting class II expression.
An earlier revolution: genetic and genomic analyses reveal pre-existing cultural differences leading to Neolithization
Authors: Leonardi Michela , Barbujani Guido , Manica Andrea 
Published: June 2017

AbstractArchaeological evidence shows that, in the long run, Neolitization (the transition from foraging to food production) was associated with demographic growth. We used two methods (patterns of linkage disequilibrium from whole-genome SNPs and MSMC estimates on genomes) to reconstruct the demographic profiles for respectively 64 and 24 modern-day populations with contrasting lifestyles across the Old World (sub-Saharan Africa, south-eastern Asia, Siberia). Surprisingly, in all regions, food producers had larger effective population sizes (Ne) than foragers already 20 k years ago, well before the Neolithic revolution. As expected, this difference further increased ~12–10 k years ago, around or just before the onset of food production. Using paleoclimate reconstructions, we show that the early difference in Ne cannot be explained by food producers inhabiting more favorable regions. A number of mechanisms, including ancestral differences in census size, sedentism, exploitation of the natural resources, social stratification or connectivity between groups, might have led to the early differences in Ne detected in our analyses. Irrespective of the specific mechanisms involved, our results provide further evidence that long term cultural differences among populations of Palaeolithic hunter-gatherers are likely to have played an important role in the later Neolithization process.
Proboscis infection route of Beauveria bassiana triggers early death of Anopheles mosquito
Authors: Ishii Minehiro , Kanuka Hirotaka , Badolo Athanase , Sagnon N’Falé , Guelbeogo Wamdaogo M. , Koike Masanori , Aiuchi Daigo 
Published: June 2017

AbstractEntomopathogenic fungi are known to control vector mosquito populations. Thus, understanding the infection dynamics of entomopathogenic fungi is crucial for the effective control of insect pests such as mosquitoes. We investigated the dynamics of Beauveria bassiana s.l. 60-2 infection of Anopheles stephensi by exposing the mosquito to fungus-impregnated filter paper through two infection routes and then comparing the mortality and extent of infection. Fungal development was observed after using this inoculation method with both the tarsus route and the proboscis route, but early mosquito death occurred only after infection through the proboscis route. Fungal hyphae invaded almost all the tissues and organs before or after the death of the host, and fungal invasion of the brain was highly correlated with mortality. Moreover, although all mosquitoes that were alive at various time points after inoculation showed no fungal infection in the brain, fungal infection was detected in the brain in all dead mosquitoes. Our results suggest that fungal invasion of the brain represents one of the factors affecting mortality, and that the proboscis route of infection is critical for the early death of vector mosquitoes.
Combination of scanning probe technology with photonic nanojets
Authors: Duocastella Martí , Tantussi Francesco , Haddadpour Ali , Zaccaria Remo Proietti , Jacassi Andrea , Veronis Georgios , Diaspro Alberto , Angelis Francesco De 
Published: June 2017

AbstractLight focusing through a microbead leads to the formation of a photonic nanojet functional for enhancing the spatial resolution of traditional optical systems. Despite numerous works that prove this phenomenon, a method to appropriately translate the nanojet on top of a region of interest is still missing. Here, by using advanced 3D fabrication techniques we integrated a microbead on an AFM cantilever thus realizing a system to efficiently position nanojets. This fabrication approach is robust and can be exploited in a myriad of applications, ranging from microscopy to Raman spectroscopy. We demonstrate the potential of portable nanojets by imaging different sub-wavelength structures. Thanks to the achieved portability, we were able to perform a detailed optical characterization of the resolution enhancement induced by the microbead, which sheds light into the many contradictory resolution claims present in literature. Our conclusions are strongly supported by rigorous data analysis and by numerical simulations, all in perfect agreement with experimental results.
Flat Terahertz Reflective Focusing Metasurface with Scanning Ability
Authors: Yi Huan , Qu Shi-Wei , Chen Bao-Jie , Bai Xue , Ng Kung Bo , Chan Chi Hou 
Published: June 2017

AbstractThe ability to manipulate the propagation properties of electromagnetic waves, e.g., divergence, focusing, holography or deflection, is very significant in terahertz applications. Metasurfaces with flat structures are attractive for achieving such manipulations in terahertz band, as they feature low profile, lightweight, and ease of design and installation. Several types of terahertz reflective or transmitting metasurfaces with focusing function have been implemented recently, but none of them can provide scanning ability with controllable focus. Here, a flat reflective metasurface featuring controllable focal shift is proposed and experimentally demonstrated. Furthermore, the principle of designing a focus scanning reflective metasurface is presented and the focusing characteristics are discussed, including focus scanning along a line parallel or orthogonal to the metasurface with a large bandwidth. These interesting properties indicate that this flat reflective metasurface could play a key role in many terahertz imaging and detection systems.
Divergent Anabolic Signalling responses of Murine Soleus and Tibialis Anterior Muscles to Chronic 2G Hypergravity
Authors: Mirzoev Timur , Tyganov Sergey , Petrova Irina , Gnyubkin Vasily , Laroche Norbert , Vico Laurence , Shenkman Boris 
Published: June 2017

AbstractThe purpose of the study was to assess the rate of protein synthesis (PS) and elucidate signalling pathways regulating PS in mouse soleus (Sol) and tibialis anterior (TA) muscles following chronic hypergravity (30-day centrifugation at 2G). The content of the key signalling proteins of the various anabolic signalling pathways was determined by Western-blotting. The rate of PS was assessed using in-vivo SUnSET technique. An exposure to 2G centrifugation did not induce any significant changes in the rate of PS as well as phosphorylation status of the key anabolic markers (AKT, p70s6k, 4E-BP1, GSK-3beta, eEF2) in Sol. On the contrary, a significant 55% increase in PS (p < 0.05) was found in TA. The cause of such a rise in PS could be associated with an increase in AKT (+72%, p < 0.05), GSK-3beta (+60%, p < 0.05) and p70s6k (+40%, p < 0.05) phosphorylation, as well as a decrease in eEF2 phosphorylation (−46%, p < 0.05) as compared to control values. Thus, the results of our study indicate that 30-day 2G centrifugation induces a distinct anabolic response in mouse Sol and TA muscles. The activation of the PS rate in TA could be linked to an up-regulation of both mTORC1-dependent and mTORC1-independent signalling pathways.
IL-6 secretion in osteoarthritis patients is mediated by chondrocyte-synovial fibroblast cross-talk and is enhanced by obesity
Authors: Pearson Mark J. , Herndler-Brandstetter Dietmar , Tariq Mohammad A. , Nicholson Thomas A. , Philp Ashleigh M. , Smith Hannah L. , Davis Edward T. , Jones Simon W. , Lord Janet M. 
Published: June 2017

AbstractIncreasing evidence suggests that inflammation plays a central role in driving joint pathology in certain patients with osteoarthritis (OA). Since many patients with OA are obese and increased adiposity is associated with chronic inflammation, we investigated whether obese patients with hip OA exhibited differential pro-inflammatory cytokine signalling and peripheral and local lymphocyte populations, compared to normal weight hip OA patients. No differences in either peripheral blood or local lymphocyte populations were found between obese and normal-weight hip OA patients. However, synovial fibroblasts from obese OA patients were found to secrete greater amounts of the pro-inflammatory cytokine IL-6, compared to those from normal-weight patients (p < 0.05), which reflected the greater levels of IL-6 detected in the synovial fluid of the obese OA patients. Investigation into the inflammatory mechanism demonstrated that IL-6 secretion from synovial fibroblasts was induced by chondrocyte-derived IL-6. Furthermore, this IL-6 inflammatory response, mediated by chondrocyte-synovial fibroblast cross-talk, was enhanced by the obesity-related adipokine leptin. This study suggests that obesity enhances the cross-talk between chondrocytes and synovial fibroblasts via raised levels of the pro-inflammatory adipokine leptin, leading to greater production of IL-6 in OA patients.
Lipid vesicles containing transferrin receptor binding peptide TfR-T12 and octa-arginine conjugate stearyl-R8 efficiently treat brain glioma along with glioma stem cells
Authors: Mu Li-Min , Bu Ying-Zi , Liu Lei , Xie Hong-Jun , Ju Rui-Jun , Wu Jia-Shuan , Zeng Fan , Zhao Yao , Zhang Jing-Ying , Lu Wan-Liang 
Published: June 2017

AbstractSurgery and radiotherapy cannot fully remove brain glioma; thus, chemotherapy continues to play an important role in treatment of this illness. However, because of the restriction of the blood-brain barrier (BBB) and the regeneration of glioma stem cells, post-chemotherapy relapse usually occurs. Here, we report a potential solution to these issues that involves a type of novel multifunctional vinblastine liposomes equipped with transferrin receptor binding peptide TfR-T12 and octa-arginine conjugate stearyl-R8. Studies were performed on brain glioma and glioma stem cells in vitro and were verified in brain glioma-bearing mice. The liposomes were transported across the BBB, killing brain glioma and glioma stem cells via the induction of necrosis, apoptosis and autophagy. Furthermore, we reveal the molecular mechanisms for treating brain glioma and glioma stem cells via functionalized drug lipid vesicles.
Novel regulatory mechanism of serine biosynthesis associated with 3-phosphoglycerate dehydrogenase in Arabidopsis thaliana
Authors: Okamura Eiji , Hirai Masami Yokota 
Published: June 2017

AbstractThe proteinogenic amino acid l-serine is a precursor for various essential biomolecules in all organisms. 3-Phosphoglycerate dehydrogenase (PGDH) is the first committed enzyme of the phosphorylated pathway of l-serine biosynthesis, and is regulated by negative feedback from l-serine in bacteria and plants. In the present study, two Arabidopsis PGDH isoforms were inhibited by l-serine but were activated by l-amino acids such as l-homocysteine in vitro. Activation and inhibition by these amino acids was cooperative, suggesting an allosteric mechanism. Moreover, the half maximal effective concentration of l-homocysteine was 2 orders of magnitude lower than that of l-serine, suggesting greater regulatory potency. These are the first data to show that PGDH is activated by various biomolecules and indicate that serine biosynthesis is regulated by multiple pathways.
Reduction in Migratory Phenotype in a Metastasized Breast Cancer Cell Line via Downregulation of S100A4 and GRM3
Authors: Chen Andy , Wang Luqi , Li Bai-Yan , Sherman Jesse , Ryu Jong E. , Hamamura Kazunori , Liu Yunlong , Nakshatri Harikrishna , Yokota Hiroki 
Published: June 2017

AbstractTo investigate phenotypic and genotypic alterations before and after bone metastasis, we conducted genome-wide mRNA profiling and DNA exon sequencing of two cell lines (TMD and BMD) derived from a mouse xenograft model. TMD cells were harvested from the mammary fat pad after transfecting MDA-MB-231 breast cancer cells, while BMD cells were isolated from the metastasized bone. Compared to BMD cells, TMD cells exhibited higher cellular motility. In contrast, BMD cells formed a spheroid with a smoother and more circular surface when co-cultured with osteoblasts. In characterizing mRNA expression using principal component analysis, S100 calcium-binding protein A4 (S100A4) was aligned to a principal axis associated with metastasis. Partial silencing of S100A4 suppressed migratory capabilities of TMD cells, while Paclitaxel decreased the S100A4 level and reduced TMD’s cellular motility. DNA mutation analysis revealed that the glutamate metabotropic receptor 3 (GRM3) gene gained a premature stop codon in BMD cells, and silencing GRM3 in TMD cells altered their spheroid shape closer to that of BMD cells. Collectively, this study demonstrates that metastasized cells are less migratory due in part to the post-metastatic downregulation of S100A4 and GRM3. Targeting S100A4 and GRM3 may help prevent bone metastasis.
Anti-leukemia activity of a Hsp70 inhibitor and its hybrid molecules
Authors: Park Seong-Hyun , Kim Won-Je , Li Hui , Seo Wonil , Park Sang-Hyun , Kim Hwan , Shin Sang Chul , Zuiderweg Erik R. P. , Kim Eunice EunKyeong , Sim Taebo , Kim Nak-Kyoon , Shin Injae 
Published: June 2017

AbstractIn this study we examined the anti-leukemia activity of a small molecule inhibitor of Hsp70 proteins, apoptozole (Az), and hybrids in which it is linked to an inhibitor of either Hsp90 (geldanamycin) or Abl kinase (imatinib). The results of NMR studies revealed that Az associates with an ATPase domain of Hsc70 and thus blocks ATP binding to the protein. Observations made in the cell study indicated that Az treatment promotes leukemia cell death by activating caspase-dependent apoptosis without affecting the caspase-independent apoptotic pathway. Importantly, the hybrids composed of Az and geldanamycin, which have high inhibitory activities towards both Hsp70 and Hsp90, exhibit enhanced anti-leukemia activity relative to the individual inhibitors. However, the Az and imatinib hybrids have weak inhibitory activities towards Hsp70 and Abl, and display lower cytotoxicity against leukemia cells compared to those of the individual constituents. The results of a mechanistic study showed that the active hybrid molecules promote leukemia cell death through a caspase-dependent apoptotic pathway. Taken together, the findings suggest that Hsp70 inhibitors as well as their hybrids can serve as potential anti-leukemia agents.
Interaction-induced edge states in anisotropic non-Fermi liquids
Authors: Yurkevich I. V. 
Published: June 2017

AbstractWe devise an approach to calculation of scaling dimensions of generic operators describing scattering within multi-channel Luttinger liquid. The local impurity scattering in arbitrary configuration of conducting and insulating channels is investigated and the problem is reduced to a single algebraic matrix equation. The application to a semi-infinite array of chains described by Luttinger liquid models demonstrates that for a weak inter-chain hybridisation and intra-channel electron-electron attraction the edge wire is robust against disorder whereas bulk wires, on contrary, become insulating in some region of inter-chain interaction parameters. This result proves that the edge states may exist in disordered anisotropic strongly correlated systems without time-reversal symmetry breaking or spin-orbit interaction and provide quantized low-temperature transport.
Improving the detection of pathways in genome-wide association studies by combined effects of SNPs from Linkage Disequilibrium blocks
Authors: Zhao Huiying , Nyholt Dale R. , Yang Yuanhao , Wang Jihua , Yang Yuedong 
Published: June 2017

AbstractGenome-wide association studies (GWAS) have successfully identified single variants associated with diseases. To increase the power of GWAS, gene-based and pathway-based tests are commonly employed to detect more risk factors. However, the gene- and pathway-based association tests may be biased towards genes or pathways containing a large number of single-nucleotide polymorphisms (SNPs) with small P-values caused by high linkage disequilibrium (LD) correlations. To address such bias, numerous pathway-based methods have been developed. Here we propose a novel method, DGAT-path, to divide all SNPs assigned to genes in each pathway into LD blocks, and to sum the chi-square statistics of LD blocks for assessing the significance of the pathway by permutation tests. The method was proven robust with the type I error rate >1.6 times lower than other methods. Meanwhile, the method displays a higher power and is not biased by the pathway size. The applications to the GWAS summary statistics for schizophrenia and breast cancer indicate that the detected top pathways contain more genes close to associated SNPs than other methods. As a result, the method identified 17 and 12 significant pathways containing 20 and 21 novel associated genes, respectively for two diseases. The method is available online by http://sparks-lab.org/server/DGAT-path.
Increased levels of ascorbic acid in the cerebrospinal fluid of cognitively intact elderly patients with major depression: a preliminary study
Authors: Hashimoto Kenji , Ishima Tamaki , Sato Yasunori , Bruno Davide , Nierenberg Jay , Marmar Charles R. , Zetterberg Henrik , Blennow Kaj , Pomara Nunzio 
Published: June 2017

AbstractMajor depressive disorder (MDD) in the elderly is a risk factor for dementia, but the precise biological basis remains unknown, hampering the search for novel biomarkers and treatments. In this study, we performed metabolomics analysis of cerebrospinal fluid (CSF) from cognitively intact elderly patients (N = 28) with MDD and age- and gender-matched healthy controls (N = 18). The CSF levels of 177 substances were measured, while 288 substances were below the detection limit. Only ascorbic acid was significantly different, with higher levels in the MDD group at baseline. There were no correlations between CSF ascorbic acid levels and clinical variables in MDD patients at baseline. At the 3-year follow-up, there was no difference of CSF ascorbic acid levels between the two groups. There was a negative correlation between CSF ascorbic acid and CSF amyloid-β42 levels in all subjects. However, there were no correlations between ascorbic acid and other biomarkers (e.g., amyloid-β40, total and phosphorylated tau protein). This preliminary study suggests that abnormalities in the transport and/or release of ascorbic acid might play a role in the pathogenesis of late-life depression.
Small head size and delayed body weight growth in wild Japanese monkey fetuses after the Fukushima Daiichi nuclear disaster
Authors: Hayama Shin-ichi , Tsuchiya Moe , Ochiai Kazuhiko , Nakiri Sachie , Nakanishi Setsuko , Ishii Naomi , Kato Takuya , Tanaka Aki , Konno Fumiharu , Kawamoto Yoshi , Omi Toshinori 
Published: June 2017

AbstractTo evaluate the biological effect of the Fukushima Daiichi nuclear disaster, relative differences in the growth of wild Japanese monkeys (Macaca fuscata) were measured before and after the disaster of 2011 in Fukushima City, which is approximately 70 km from the nuclear power plant, by performing external measurements on fetuses collected from 2008 to 2016. Comparing the relative growth of 31 fetuses conceived prior to the disaster and 31 fetuses conceived after the disaster in terms of body weight and head size (product of the occipital frontal diameter and biparietal diameter) to crown-rump length ratio revealed that body weight growth rate and proportional head size were significantly lower in fetuses conceived after the disaster. No significant difference was observed in nutritional indicators for the fetuses’ mothers. Accordingly, radiation exposure could be one factor contributed to the observed growth delay in this study.