bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model
Authors: Alhabbab R. , Blair P. , Elgueta R. , Stolarczyk E. , Marks E. , Becker P. D. , Ratnasothy K. , Smyth L. , Safinia N. , Sharif-Paghaleh E. , O’Connell S. , Noelle R. J. , Lord G. M. , Howard J. K. , Spencer J. , Lechler R. I. , Lombardi G. 
Published: June 2015

AbstractB cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that B cells can contribute to the maintenance of tolerance. Here, we used a mouse model of MHC-class I mismatched skin transplantation to investigate the contribution of B cells to graft survival. We demonstrate that adoptive transfer of B cells prolongs skin graft survival but only when the B cells were isolated from mice housed in low sterility “conventional” (CV) facilities and not from mice housed in pathogen free facilities (SPF). However, prolongation of skin graft survival was lost when B cells were isolated from IL-10 deficient mice housed in CV facilities. The suppressive function of B cells isolated from mice housed in CV facilities correlated with an anti-inflammatory environment and with the presence of a different gut microflora compared to mice maintained in SPF facilities. Treatment of mice in the CV facility with antibiotics abrogated the regulatory capacity of B cells. Finally, we identified transitional B cells isolated from CV facilities as possessing the regulatory function. These findings demonstrate that B cells and in particular transitional B cells, can promote prolongation of graft survival, a function dependent on licensing by gut microflora.
Acrylamide toxic effects on mouse oocyte quality and fertility in vivo
Authors: Duan Xing , Wang Qiao-Chu , Chen Kun-Lin , Zhu Cheng-Cheng , Liu Jun , Sun Shao-Chen 
Published: June 2015

AbstractAcrylamide is an industrial chemical that has attracted considerable attention due to its presumed carcinogenic, neurotoxic and cytotoxic effects. In this study we investigated possible acrylamide reproductive toxic effects in female mice. Mice were fed an acrylamide-containing diet for 6 weeks. Our results showed the following effects of an acrylamide-containing diet. (1) Ovary weights were reduced in acrylamide-treated mice and oocyte developmental competence was also reduced, as shown by reduced GVBD and polar body extrusion rates. (2) Acrylamide feeding resulted in aberrant oocyte cytoskeletons, as shown by an increased abnormal spindle rate and confirmed by disrupted γ-tubulin and p-MAPK localization. (3) Acrylamide feeding resulted in oxidative stress and oocyte early stage apoptosis, as shown by increased ROS levels and p-MAPK expression. (4) Fluorescence intensity analysis showed that DNA methylation levels were reduced in acrylamide-treated oocytes and histone methylation levels were also altered, as H3K9me2, H3K9me3, H3K4me2 and H3K27me3 levels were reduced after acrylamide treatment. (5) After acrylamide feeding, the litter sizes of acrylamide-treated mice were significantly smaller compared to thus of control mice. Thus, our results indicated that acrylamide might affect oocyte quality through its effects on cytoskeletal integrity, ROS generation, apoptosis induction and epigenetic modifications.
Phosphorylation of Beet black scorch virus coat protein by PKA is required for assembly and stability of virus particles
Authors: Zhao Xiaofei , Wang Xiaoling , Dong Kai , Zhang Yongliang , Hu Yue , Zhang Xin , Chen Yanmei , Wang Xianbing , Han Chenggui , Yu Jialin , Li Dawei 
Published: June 2015

AbstractPlant virus coat proteins (CPs) play a fundamental role in protection of genomic RNAs, virion assembly and viral movement. Although phosphorylation of several CPs during virus infection have been reported, little information is available about CP phosphorylation of the spherical RNA plant viruses. Here, we demonstrate that the CP of Beet black scorch virus (BBSV), a member of the genus Necrovirus, can be phosphorylated at threonine-41 (T41) by cAMP-dependent protein kinase (PKA)-like kinase in vivo and in vitro. Mutant viruses containing a T41A non-phosphorylatable alanine substitution and a T41E glutamic acid substitution to mimic threonine phosphorylation were able to replicate but were unable to move systemically in Nicotiana benthamiana. Interestingly, the T41A and T41E mutants generated unstable 17 nm virus-like particles that failed to package viral genomic (g) RNA, compared with wild-type BBSV with 30 nm virions during viral infection in N. benthamiana. Further analyses showed that the T41 mutations had little effect on the gRNA-binding activity of the CP. Therefore, we propose a model whereby CP phosphorylation plays an essential role in long-distance movement of BBSV that involves formation of stable virions.
RAD51 135G>C substitution increases breast cancer risk in an ethnic-specific manner: a meta-analysis on 21236 cases and 19407 controls
Authors: Sekhar Deepa , Pooja Singh , Kumar Sandeep , Rajender Singh 
Published: June 2015

AbstractRAD51 is a homolog of bacterial RecA protein, which plays an important role in preserving stability of the genome. RAD51 interacts with BRCA1 and BRCA2 for homologous recombination repair. A functional polymorphism (135G > C) in the RAD51 gene has been a subject of great interest, which is evidenced by at least 28 case-control studies and eight meta-analyses undertaken on this polymorphism till now. We undertook a meta-analysis on RAD51 135G > C data for 21236 cases and 19407 controls pooled from 28 studies on breast cancer in women. Pooled data analysis suggested a significant association of the substitution with breast cancer in the recessive model (GG + GC versus CC) and in the co-dominant models comparing GG versus CC and GC versus CC. Analysis of the results suggested that ‘CC’ genotype is a significant breast cancer risk factor in comparison to ‘GG’ and ‘GC’ genotypes. We also undertook pooled analyses on different ethnic groups and found that ‘CC’ was a strong risk factor in Caucasians, but not in East-Asians and populations of mixed ethnicity. In conclusion, the RAD51 135G > C substitution in the homozygous form (CC) increases the risk of breast cancer in an ethnic-specific manner.
Ultrathin Carbon with Interspersed Graphene/Fullerene-like Nanostructures: A Durable Protective Overcoat for High Density Magnetic Storage
Authors: Dwivedi Neeraj , Satyanarayana Nalam , Yeo Reuben J. , Xu Hai , Ping Loh Kian , Tripathy Sudhiranjan , Bhatia Charanjit S. 
Published: June 2015

AbstractOne of the key issues for future hard disk drive technology is to design and develop ultrathin (<2 nm) overcoats with excellent wear- and corrosion protection and high thermal stability. Forming carbon overcoats (COCs) having interspersed nanostructures by the filtered cathodic vacuum arc (FCVA) process can be an effective approach to achieve the desired target. In this work, by employing a novel bi-level surface modification approach using FCVA, the formation of a high sp3 bonded ultrathin (~1.7 nm) amorphous carbon overcoat with interspersed graphene/fullerene-like nanostructures, grown on magnetic hard disk media, is reported. The in-depth spectroscopic and microscopic analyses by high resolution transmission electron microscopy, scanning tunneling microscopy, time-of-flight secondary ion mass spectrometry and Raman spectroscopy support the observed findings. Despite a reduction of ~37 % in COC thickness, the FCVA-processed thinner COC (~1.7 nm) shows promising functional performance in terms of lower coefficient of friction (~0.25), higher wear resistance, lower surface energy, excellent hydrophobicity and similar/better oxidation corrosion resistance than current commercial COCs of thickness ~2.7 nm. The surface and tribological properties of FCVA-deposited COC was further improved after deposition of lubricant layer.
Hypertrophic scar contracture is mediated by the TRPC3 mechanical force transducer via NFkB activation
Authors: Ishise Hisako , Larson Barrett , Hirata Yutaka , Fujiwara Toshihiro , Nishimoto Soh , Kubo Tateki , Matsuda Ken , Kanazawa Shigeyuki , Sotsuka Yohei , Fujita Kazutoshi , Kakibuchi Masao , Kawai Kenichiro 
Published: June 2015

AbstractWound healing process is a complex and highly orchestrated process that ultimately results in the formation of scar tissue. Hypertrophic scar contracture is considered to be a pathologic and exaggerated wound healing response that is known to be triggered by repetitive mechanical forces. We now show that Transient Receptor Potential (TRP) C3 regulates the expression of fibronectin, a key regulatory molecule involved in the wound healing process, in response to mechanical strain via the NFkB pathway. TRPC3 is highly expressed in human hypertrophic scar tissue and mechanical stimuli are known to upregulate TRPC3 expression in human skin fibroblasts in vitro. TRPC3 overexpressing fibroblasts subjected to repetitive stretching forces showed robust expression levels of fibronectin. Furthermore, mechanical stretching of TRPC3 overexpressing fibroblasts induced the activation of nuclear factor-kappa B (NFκB), a regulator fibronectin expression, which was able to be attenuated by pharmacologic blockade of either TRPC3 or NFκB. Finally, transplantation of TRPC3 overexpressing fibroblasts into mice promoted wound contraction and increased fibronectin levels in vivo. These observations demonstrate that mechanical stretching drives fibronectin expression via the TRPC3-NFkB axis, leading to intractable wound contracture. This model explains how mechanical strain on cutaneous wounds might contribute to pathologic scarring.
Sox2-CreER mice are useful for fate mapping of mature, but not neonatal, cochlear supporting cells in hair cell regeneration studies
Authors: Walters Bradley J. , Yamashita Tetsuji , Zuo Jian 
Published: June 2015

AbstractStudies of hair cell regeneration in the postnatal cochlea rely on fate mapping of supporting cells. Here we characterized a Sox2-CreER knock-in mouse line with two independent reporter mouse strains at neonatal and mature ages. Regardless of induction age, reporter expression was robust, with CreER activity being readily detectable in >85% of supporting cells within the organ of Corti. When induced at postnatal day (P) 28, Sox2-CreER activity was exclusive to supporting cells demonstrating its utility for fate mapping studies beyond this age. However, when induced at P1, Sox2-CreER activity was also detected in >50% of cochlear hair cells, suggesting that Sox2-CreER may not be useful to fate map a supporting cell origin of regenerated hair cells if induced at neonatal ages. Given that this model is currently in use by several investigators for fate mapping purposes and may be adopted by others in the future, our finding that current protocols are effective for restricting CreER activity to supporting cells at mature but not neonatal ages is both significant and timely.
Pancreatic alpha-cells from female mice undergo morphofunctional changes during compensatory adaptations of the endocrine pancreas to diet-induced obesity
Authors: Merino Beatriz , Alonso-Magdalena Paloma , Lluesma Mónica , Ñeco Patricia , Gonzalez Alejandro , Marroquí Laura , García-Arévalo Marta , Nadal Angel , Quesada Ivan 
Published: June 2015

AbstractObesity is frequently associated with insulin resistance. To compensate for this situation and maintain normoglycaemia, pancreatic beta-cells undergo several morphofunctional adaptations, which result in insulin hypersecretion and hyperinsulinaemia. However, no information exists about pancreatic alpha-cells during this compensatory stage of obesity. Here, we studied alpha-cells in mice fed a high-fat diet (HFD) for 12 weeks. These animals exhibited hyperinsulinaemia and normoglycaemia compared with control animals in addition to hypoglucagonaemia. While the in vivo response of glucagon to hypoglycaemia was preserved in the obese mice, the suppression of glucagon secretion during hyperglycaemia was impaired. Additionally, in vitro glucagon release at low glucose levels and glucagon content in isolated islets were decreased, while alpha-cell exocytosis remained unchanged. Assessment of morphological parameters revealed that alpha-cell area was reduced in the pancreas of the obese mice in association with alpha-cell hypotrophy, increased apoptosis and decreased proliferation. HFD feeding for 24 weeks led to significant deterioration in beta-cell function and glucose homeostasis. Under these conditions, the majority of alpha-cell changes were reversed and became comparable to controls. These findings indicate that pancreatic compensatory adaptations during obesity may also involve pancreatic alpha-cells. Additionally, defects in alpha-cell function during obesity may be implicated in progression to diabetes.
Beyond Gisin’s Theorem and its Applications: Violation of Local Realism by Two-Party Einstein-Podolsky-Rosen Steering
Authors: Chen Jing-Ling , Su Hong-Yi , Xu Zhen-Peng , Wu Yu-Chun , Wu Chunfeng , Ye Xiang-Jun , Żukowski Marek , Kwek L. C. 
Published: June 2015

AbstractWe demonstrate here that for a given mixed multi-qubit state if there are at least two observers for whom mutual Einstein-Podolsky-Rosen steering is possible, i.e. each observer is able to steer the other qubits into two different pure states by spontaneous collapses due to von Neumann type measurements on his/her qubit, then nonexistence of local realistic models is fully equivalent to quantum entanglement (this is not so without this condition). This result leads to an enhanced version of Gisin’s theorem (originally: all pure entangled states violate local realism). Local realism is violated by all mixed states with the above steering property. The new class of states allows one e.g. to perform three party secret sharing with just pairs of entangled qubits, instead of three qubit entanglements (which are currently available with low fidelity). This significantly increases the feasibility of having high performance versions of such protocols. Finally, we discuss some possible applications.
Development of trastuzumab-resistant human gastric carcinoma cell lines and mechanisms of drug resistance
Authors: Zuo Qiang , Liu Jing , Zhang Jingwen , Wu Mengwan , Guo Lihong , Liao Wangjun 
Published: June 2015

AbstractTrastuzumab has been successfully employed for the treatment of Her-2-positive gastric cancer. However, there are problems with both primary and secondary resistance to trastuzumab. In this study, we employed the human gastric carcinoma cell line NCI-N87 with high Her-2 expression to create trastuzumab-resistant NCI-N87/TR cells by stepwise exposure to increasing doses of trastuzumab. Western blotting and Real-time PCR were conducted to detect protein and gene levels. Compared with NCI-N87 cells, the expression of P-IGF-1R and P-AKT proteins was significantly increased in NCI-N87/TR cells (both P = 0.000), while PTEN gene and protein expression showed a significant decrease (both P = 0.000). In addition, mutations of the PTEN gene were detected at exons 5, 7 and 8. The sensitivity of NCI-N87/TR cells to trastuzumab was increased by transfection with the PTEN gene, or by incubation with a PI3K inhibitor (LY294002) or an IGF-IR inhibitor (AG1024), as well as siRNA targeting PI3K p110 or IGF-1R. Taken together, our findings showed that activation of the PI3K-AKT signaling pathway was one of the major mechanisms leading to resistance of NCI-N87/TR gastric cancer cells to trastuzumab, which was probably associated with PTEN gene down-regulation and mutation, as well as with over-activity of the IGF-1R signaling pathway.
Altered regional activity and inter-regional functional connectivity in psychogenic non-epileptic seizures
Authors: Li Rong , Li Yibo , An Dongmei , Gong Qiyong , Zhou Dong , Chen Huafu 
Published: June 2015

AbstractAlthough various imaging studies have focused on detecting the cerebral function underlying psychogenic non-epileptic seizures (PNES), the nature of PNES remains poorly understood. In this study, we combined the resting state fMRI with fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity based on the seed voxel linear correlation approach to examine the alterations of regional and inter-regional network cerebral functions in PNES. A total of 20 healthy controls and 18 patients were enrolled. The PNES patients showed significantly increased fALFF mainly in the dorsolateral prefrontal cortex (DLPFC), parietal cortices and motor areas, as well as decreased fALFF in the triangular inferior frontal gyrus. Thus, our results add to literature suggesting abnormalities of neural synchrony in PNES. Moreover, PNES exhibited widespread inter-regional neural network deficits, including increased (DLPFC, sensorimotor and limbic system) and decreased (ventrolateral prefrontal cortex) connectivity, indicating that changes in the regional cerebral function are related to remote inter-regional network deficits. Correlation analysis results revealed that the connectivity between supplementary motor area and anterior cingulate cortex correlated with the PNES frequency, further suggesting the skewed integration of synchronous activity could predispose to the occurrence of PNES. Our findings provided novel evidence to investigate the pathophysiological mechanisms of PNES.
Nitrogen limitation as a driver of genome size evolution in a group of karst plants
Authors: Kang Ming , Wang Jing , Huang Hongwen 
Published: June 2015

AbstractGenome size is of fundamental biological importance with significance in predicting structural and functional attributes of organisms. Although abundant evidence has shown that the genome size can be largely explained by differential proliferation and removal of non-coding DNA of the genome, the evolutionary and ecological basis of genome size variation remains poorly understood. Nitrogen (N) and phosphorus (P) are essential elements of DNA and protein building blocks, yet often subject to environmental limitation in natural ecosystems. Using phylogenetic comparative methods, we test this hypothesis by determining whether leaf N and P availability affects genome sizes in 99 species of Primulina (Gesneriaceae), a group of soil specialists adapted to limestone karst environment in south China. We find that genome sizes in Primulina are strongly positively correlated with plant N content, but the correlation with plant P content is not significant when phylogeny history was taken into account. This study shows for the first time that N limitation might have been a plausible driver of genome size variation in a group of plants. We propose that competition for nitrogen nutrient between DNA synthesis and cellular functions is a possible mechanism for genome size evolution in Primulina under N-limitation.
Nanopore sensing of individual transcription factors bound to DNA
Authors: Squires Allison , Atas Evrim , Meller Amit 
Published: June 2015

AbstractTranscription factor (TF)-DNA interactions are the primary control point in regulation of gene expression. Characterization of these interactions is essential for understanding genetic regulation of biological systems and developing novel therapies to treat cellular malfunctions. Solid-state nanopores are a highly versatile class of single-molecule sensors that can provide rich information about local properties of long charged biopolymers using the current blockage patterns generated during analyte translocation and provide a novel platform for characterization of TF-DNA interactions. The DNA-binding domain of the TF Early Growth Response Protein 1 (EGR1), a prototypical zinc finger protein known as zif268, is used as a model system for this study. zif268 adopts two distinct bound conformations corresponding to specific and nonspecific binding, according to the local DNA sequence. Here we implement a solid-state nanopore platform for direct, label- and tether-free single-molecule detection of zif268 bound to DNA. We demonstrate detection of single zif268 TFs bound to DNA according to current blockage sublevels and duration of translocation through the nanopore. We further show that the nanopore can detect and discriminate both specific and nonspecific binding conformations of zif268 on DNA via the distinct current blockage patterns corresponding to each of these two known binding modes.
Universal Approach to FRAP Analysis of Arbitrary Bleaching Patterns
Authors: Blumenthal Daniel , Goldstien Leo , Edidin Michael , Gheber Levi A. 
Published: June 2015

AbstractThe original approach to calculating diffusion coefficients of a fluorescent probe from Fluorescence Recovery After Photobleaching (FRAP) measurements assumes bleaching with a circular laser beam of a Gaussian intensity profile. This method was used without imaging the bleached cell. An empirical equation for calculating diffusion coefficients from a rectangular bleaching geometry, created in a confocal image, was later published, however a single method allowing the calculation of diffusion coefficients for arbitrary geometry does not exist. Our simulation approach allows computation of diffusion coefficients regardless of bleaching geometry used in the FRAP experiment. It accepts a multiple-frame TIFF file, representing the experiment as input and simulates the (pure) diffusion of the fluorescent probes (2D random walk) starting with the first post-bleach frame of the actual data. It then fits the simulated data to the real data and extracts the diffusion coefficient. We validate our approach using a well characterized diffusing molecule (DiIC18) against well-established analytical procedures. We show that the algorithm is able to calculate the absolute value of diffusion coefficients for arbitrary bleaching geometries, including exaggeratedly large ones. It is provided freely as an ImageJ plugin and should facilitate quantitative FRAP measurements for users equipped with standard fluorescence microscopy setups.
The Missing Memristor has Not been Found
Authors: Vongehr Sascha , Meng Xiangkang 
Published: June 2015

AbstractIn 1971, not only the theoretical and by definition already existing ‘ideal memristor’ concept was introduced, but a real memristor device was suggested on grounds of the already known real inductors. The latter is a scientifically significant hypothesis grounded in fundamental symmetries of basic physics, here electro-magnetism. 2008 claimed the discovery of the “missing memristor.” Controversy arose: The devices were not new and the hypothesized device needs magnetism but has no material memory, while the available devices constitute analogue memory that would work in a world without magnetism. Nevertheless, even the originator of the prediction accepted the discovery. Defenders of the 2008 claim emphasize that the devices are not merely ‘memristive systems,’ which is however a distinction defined in 1976, not 1971. We clarify widely confused concepts and maintain that the originally hypothesized real memristor device is missing and likely impossible. The argument is illustrated also by finding an ideal mechanical memristor element and purely mechanical memristive systems and hypothesizing a real mechanical memristor device that requires inert mass just like the 1971 implied device requires magnetic induction.