bluuebunny/crossref_metadata_2025_split huggingface dataset:
Necrosis- and apoptosis-related Met cleavages have divergent functional consequences
Authors: Montagne R , Berbon M , Doublet L , Debreuck N , Baranzelli A , Drobecq H , Leroy C , Delhem N , Porte H , Copin M-C , Dansin E , Furlan A , Tulasne D 
Published: May 2015

AbstractUpon activation by its ligand hepatocyte growth factor/scatter factor, the receptor tyrosine kinase Met promotes survival, proliferation, and migration of epithelial cells during embryogenesis. Deregulated Met signaling can also promote cancer progression and metastasis. Met belongs to the functional family of dependence receptors whose activity switches from pro-survival to pro-apoptotic during apoptosis upon caspase cleavage. Although apoptosis resistance is a hallmark of cancer cells, some remain sensitive to other cell death processes, including necrosis induced by calcium stress. The role and fate of Met during necrotic cell death are unknown. Following treatment with calcium ionophores, cell lines and primary cells undergo necrosis, and the full-length Met receptor is efficiently degraded. This degradation is achieved by double cleavage of Met in its extracellular domain by a metalloprotease of the A disintegrin and metalloproteinase (ADAM) family and in its intracellular domain by calpains (calcium-dependent proteases). These cleavages separate the Met extracellular region from its kinase domain, thus preventing Met activity and its potential pro-survival activity. Although the intracellular fragment is very similar to the fragment generated by caspases, it displays no pro-apoptotic property, likely because of the presence of the last few amino acids of Met, known to inhibit this pro-apoptotic function. The fragments identified here are observed in lung tumors overexpressing the Met receptor, along with fragments previously identified, suggesting that proteolytic cleavages of Met are involved in its degradation in tumor tissues. Thus, Met is a modulator of necrosis, able to protect cells when activated by its ligand but efficiently degraded by proteolysis when this process is engaged.
Epigallocatechin-3-gallate opposes HBV-induced incomplete autophagy by enhancing lysosomal acidification, which is unfavorable for HBV replication
Authors: Zhong L , Hu J , Shu W , Gao B , Xiong S 
Published: May 2015

AbstractEpigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, exhibits diverse beneficial properties, including antiviral activity. Autophagy is a cellular process that is involved in the degradation of long-lived proteins and damaged organelles. Recent evidence indicates that modulation of autophagy is a potential therapeutic strategy for various viral diseases. In the present study, we investigated the effect of EGCG on hepatitis B virus (HBV) replication and the possible involvement of autophagy in this process. Our results showed that HBV induced autophagosome formation, which was required for replication of itself. However, although EGCG efficiently inhibited HBV replication, it enhanced, but not inhibited, autophagosome formation in hepatoma cells. Further study showed that HBV induced an incomplete autophagy, while EGCG, similar to starvation, was able to induce a complete autophagic process, which appeared to be unfavorable for HBV replication. Furthermore, it was found that HBV induced an incomplete autophagy by impairing lysosomal acidification, while it lost this ability in the presence of EGCG. Taken together, these data demonstrated that EGCG treatment opposed HBV-induced incomplete autophagy via enhancing lysosomal acidification, which was unfavorable for HBV replication.
Activation of NRG1-ERBB4 signaling potentiates mesenchymal stem cell-mediated myocardial repairs following myocardial infarction
Authors: Liang X , Ding Y , Zhang Y , Chai Y-H , He J , Chiu S-M , Gao F , Tse H-F , Lian Q 
Published: May 2015

AbstractMesenchymal stem cell (MSC) transplantation has achieved only modest success in the treatment of ischemic heart disease owing to poor cell viability in the diseased microenvironment. Activation of the NRG1 (neuregulin1)-ERBB4 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) signaling pathway has been shown to stimulate mature cardiomyocyte cell cycle re-entry and cell division. In this connection, we aimed to determine whether overexpression of ERBB4 in MSCs can enhance their cardio-protective effects following myocardial infarction. NRG1, MSCs or MSC-ERBB4 (MSC with ERBB4 overexpression), were transplanted into mice following myocardial infarction. Superior to that of MSCs and solely NRG1, MSC-ERBB4 transplantation significantly preserved heart functions accompanied with reduced infarct size, enhanced cardiomyocyte division and less apoptosis during early phase of infarction. The transduction of ERBB4 into MSCs indeed increased cell mobility and apoptotic resistance under hypoxic and glucose-deprived conditions via a PI3K/Akt signaling pathway in the presence of NRG1. Unexpectedly, introduction of ERBB4 into MSC in turn potentiates NRG1 synthesis and secretion, thus forming a novel NRG1-ERBB4-NRG1 autocrine loop. Conditioned medium of MSC-ERBB4 containing elevated NRG1, promoted cardiomyocyte growth and division, whereas neutralization of NRG1 blunted this proliferation. These findings collectively suggest that ERBB4 overexpression potentiates MSC survival in the infarcted heart, enhances NRG1 generation to restore declining NRG1 in the infarcted region and stimulates cardiomyocyte division. ERBB4 has an important role in MSC-mediated myocardial repairs.
A common assembly module in injectisome and flagellar type III secretion sorting platforms
Authors: Notti Ryan Q. , Bhattacharya Shibani , Lilic Mirjana , Stebbins C. Erec 
Published: May 2015

AbstractTranslocating proteins across the double membrane of Gram-negative bacteria, type III secretion systems (T3SS) occur in two evolutionarily related forms: injectisomes, delivering virulence factors into host cells, and the flagellar system, secreting the polymeric filament used for motility. While both systems share related elements of a cytoplasmic sorting platform that facilitates the hierarchical secretion of protein substrates, its assembly and regulation remain unclear. Here we describe a module mediating the assembly of the sorting platform in both secretion systems, and elucidate the structural basis for segregation of homologous components among these divergent T3SS subtypes sharing a common cytoplasmic milieu. These results provide a foundation for the subtype-specific assembly of T3SS sorting platforms and will support further mechanistic analysis and anti-virulence drug design.
Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1
Authors: Cortes Adrian , Pulit Sara L. , Leo Paul J. , Pointon Jenny J. , Robinson Philip C. , Weisman Michael H. , Ward Michael , Gensler Lianne S. , Zhou Xiaodong , Garchon Henri-Jean , Chiocchia Gilles , Nossent Johannes , Lie Benedicte A. , Førre Øystein , Tuomilehto Jaakko , Laiho Kari , Bradbury Linda A. , Elewaut Dirk , Burgos-Vargas Ruben , Stebbings Simon , Appleton Louise , Farrah Claire , Lau Jonathan , Haroon Nigil , Mulero Juan , Blanco Francisco J. , Gonzalez-Gay Miguel A. , Lopez-Larrea C , Bowness Paul , Gaffney Karl , Gaston Hill , Gladman Dafna D. , Rahman Proton , Maksymowych Walter P. , Crusius J. Bart A. , van der Horst-Bruinsma Irene E. , Valle-Oñate Raphael , Romero-Sánchez Consuelo , Hansen Inger Myrnes , Pimentel-Santos Fernando M. , Inman Robert D. , Martin Javier , Breban Maxime , Wordsworth Bryan Paul , Reveille John D. , Evans David M. , de Bakker Paul I.W. , Brown Matthew A. 
Published: May 2015

AbstractAnkylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.
Large-scale spatiotemporal spike patterning consistent with wave propagation in motor cortex
Authors: Takahashi Kazutaka , Kim Sanggyun , Coleman Todd P. , Brown Kevin A. , Suminski Aaron J. , Best Matthew D. , Hatsopoulos Nicholas G. 
Published: May 2015

AbstractAggregate signals in cortex are known to be spatiotemporally organized as propagating waves across the cortical surface, but it remains unclear whether the same is true for spiking activity in individual neurons. Furthermore, the functional interactions between cortical neurons are well documented but their spatial arrangement on the cortical surface has been largely ignored. Here we use a functional network analysis to demonstrate that a subset of motor cortical neurons in non-human primates spatially coordinate their spiking activity in a manner that closely matches wave propagation measured in the beta oscillatory band of the local field potential. We also demonstrate that sequential spiking of pairs of neuron contains task-relevant information that peaks when the neurons are spatially oriented along the wave axis. We hypothesize that the spatial anisotropy of spike patterning may reflect the underlying organization of motor cortex and may be a general property shared by other cortical areas.
Three-dimensional positioning and control of colloidal objects utilizing engineered liquid crystalline defect networks
Authors: Yoshida H. , Asakura K. , Fukuda J. , Ozaki M. 
Published: May 2015

AbstractTopological defects in liquid crystals not only affect the optical and rheological properties of the host, but can also act as scaffolds in which to trap nano or micro-sized colloidal objects. The creation of complex defect shapes, however, often involves confining the liquid crystals in curved geometries or adds complex-shaped colloidal objects, which are unsuitable for device applications. Using topologically patterned substrates, here we demonstrate the controlled generation of three-dimensional defect lines with non-trivial shapes and even chirality, in a flat slab of nematic liquid crystal. By using the defect lines as templates and the electric response of the liquid crystals, colloidal superstructures are constructed, which can be reversibly reconfigured at a voltage as low as 1.3 V. Three-dimensional engineering of the defect shapes in liquid crystals is potentially useful in the fabrication of self-healing composites and in stabilizing artificial frustrated phases.
Total synthesis of (+)-gelsemine via an organocatalytic Diels–Alder approach
Authors: Chen Xiaoming , Duan Shengguo , Tao Cheng , Zhai Hongbin , Qiu Fayang G. 
Published: May 2015

AbstractThe structurally complex alkaloid gelsemine was previously thought to have no significant biological activities, but a recent study has shown that it has potent and specific antinociception in chronic pain. While this molecule has attracted significant interests from the synthetic community, an efficient synthetic strategy is still the goal of many synthetic chemists. Here we report the asymmetric total synthesis of (+)-gelsemine, including a highly diastereoselective and enantioselective organocatalytic Diels–Alder reaction, an efficient intramolecular trans-annular aldol condensation furnishing the prolidine ring and establishing the configuration of the C20 quaternary carbon stereochemical centre. The entire gelsemine skeleton was constructed through a late-stage intramolecular SN2 substitution. The enantiomeric excess of this total synthesis is over 99%, and the overall yield is around 5%.
Essential Genes in the Core Genome of the Human Pathogen Streptococcus pyogenes
Authors: Le Breton Yoann , Belew Ashton T. , Valdes Kayla M. , Islam Emrul , Curry Patrick , Tettelin Hervé , Shirtliff Mark E. , El-Sayed Najib M. , McIver Kevin S. 
Published: May 2015

AbstractStreptococcus pyogenes (Group A Streptococcus, GAS) remains a major public health burden worldwide, infecting over 750 million people leading to over 500,000 deaths annually. GAS pathogenesis is complex, involving genetically distinct GAS strains and multiple infection sites. To overcome fastidious genetic manipulations and accelerate pathogenesis investigations in GAS, we developed a mariner-based system (Krmit) for en masse monitoring of complex mutant pools by transposon sequencing (Tn-seq). Highly saturated transposant libraries (Krmit insertions in ca. every 25 nucleotides) were generated in two distinct GAS clinical isolates, a serotype M1T1 invasive strain 5448 and a nephritogenic serotype M49 strain NZ131 and analyzed using a Bayesian statistical model to predict GAS essential genes, identifying sets of 227 and 241 of those genes in 5448 and NZ131, respectively. A large proportion of GAS essential genes corresponded to key cellular processes and metabolic pathways and 177 were found conserved within the GAS core genome established from 20 available GAS genomes. Selected essential genes were validated using conditional-expression mutants. Finally, comparison to previous essentiality analyses in S. sanguinis and S. pneumoniae revealed significant overlaps, providing valuable insights for the development of new antimicrobials to treat infections by GAS and other pathogenic streptococci.
Physiologically motivated multiplex Kuramoto model describes phase diagram of cortical activity
Authors: Sadilek Maximilian , Thurner Stefan 
Published: May 2015

AbstractWe derive a two-layer multiplex Kuramoto model from Wilson-Cowan type physiological equations that describe neural activity on a network of interconnected cortical regions. This is mathematically possible due to the existence of a unique, stable limit cycle, weak coupling and inhibitory synaptic time delays. We study the phase diagram of this model numerically as a function of the inter-regional connection strength that is related to cerebral blood flow and a phase shift parameter that is associated with synaptic GABA concentrations. We find three macroscopic phases of cortical activity: background activity (unsynchronized oscillations), epileptiform activity (highly synchronized oscillations) and resting-state activity (synchronized clusters/chaotic behaviour). Previous network models could hitherto not explain the existence of all three phases. We further observe a shift of the average oscillation frequency towards lower values together with the appearance of coherent slow oscillations at the transition from resting-state to epileptiform activity. This observation is fully in line with experimental data and could explain the influence of GABAergic drugs both on gamma oscillations and epileptic states. Compared to previous models for gamma oscillations and resting-state activity, the multiplex Kuramoto model not only provides a unifying framework, but also has a direct connection to measurable physiological parameters.
A bifractal nature of reticular patterns induced by oxygen plasma on polymer films
Authors: Bae Junwan , Lee I. J. 
Published: May 2015

AbstractPlasma etching was demonstrated to be a promising tool for generating self-organized nano-patterns on various commercial films. Unfortunately, dynamic scaling approach toward fundamental understanding of the formation and growth of the plasma-induced nano-structure has not always been straightforward. The temporal evolution of self-aligned nano-patterns may often evolve with an additional scale-invariance, which leads to breakdown of the well-established dynamic scaling law. The concept of a bifractal interface is successfully applied to reticular patterns induced by oxygen plasma on the surface of polymer films. The reticular pattern, composed of nano-size self-aligned protuberances and underlying structure, develops two types of anomalous dynamic scaling characterized by super-roughening and intrinsic anomalous scaling, respectively. The diffusion and aggregation of short-cleaved chains under the plasma environment are responsible for the regular distribution of the nano-size protuberances. Remarkably, it is uncovered that the dynamic roughening of the underlying structure is governed by a relaxation mechanism described by the Edwards-Wilkinson universality class with a conservative noise. The evidence for the basic phase, characterized by the negative roughness and growth exponents, has been elusive since its first theoretical consideration more than two decades ago.
Cloning and characterization of farnesyl pyrophosphate synthase from the highly branched isoprenoid producing diatom Rhizosolenia setigera
Authors: Ferriols Victor Marco Emmanuel N. , Yaginuma Ryoko , Adachi Masao , Takada Kentaro , Matsunaga Shigeki , Okada Shigeru 
Published: May 2015

AbstractThe diatom Rhizosolenia setigera Brightwell produces highly branched isoprenoid (HBI) hydrocarbons that are ubiquitously present in marine environments. The hydrocarbon composition of R. setigera varies between C25 and C30 HBIs depending on the life cycle stage with regard to auxosporulation. To better understand how these hydrocarbons are biosynthesized, we characterized the farnesyl pyrophosphate (FPP) synthase (FPPS) enzyme of R. setigera. An isolated 1465-bp cDNA clone contained an open reading frame spanning 1299-bp encoding a protein with 432 amino acid residues. Expression of the RsFPPS cDNA coding region in Escherichia coli produced a protein that exhibited FPPS activity in vitro. A reduction in HBI content from diatoms treated with an FPPS inhibitor, risedronate, suggested that RsFPPS supplies precursors for HBI biosynthesis. Product analysis by gas chromatography-mass spectrometry also revealed that RsFPPS produced small amounts of the cis-isomers of geranyl pyrophosphate and FPP, candidate precursors for the cis-isomers of HBIs previously characterized. Furthermore, RsFPPS gene expression at various life stages of R. setigera in relation to auxosporulation were also analyzed. Herein, we present data on the possible role of RsFPPS in HBI biosynthesis and it is to our knowledge the first instance that an FPPS was cloned and characterized from a diatom.
Meta-analysis reveals the correlation of Notch signaling with non-small cell lung cancer progression and prognosis
Authors: Yuan Xun , Wu Hua , Xu Hanxiao , Han Na , Chu Qian , Yu Shiying , Chen Yuan , Wu Kongming 
Published: May 2015

AbstractVarious studies have assessed the clinicopathological and prognostic value of Notch1 and Notch3 expression in Non-small cell lung cancer (NSCLC), but their results remain controversial. This meta-analysis was conducted to address the above issues by using a total of 19 studies involving 3663 patients. The correlations between Notch1 and Notch3 expression and clinicopathological features and NSCLC prognosis were analyzed. The meta-analysis indicated that higher expression of Notch1 was associated with greater possibility of lymph node metastasis and higher TNM stages. Moreover, patients with Notch1 overexpression and Notch3 overexpression showed significantly poor overall survival (Notch1: HR, 1.29; 95% CI, 1.06–1.57, p = 0.468 and I2 = 0.0%; Notch3: HR, 1.57; 95%CI, 1.04-2.36, p = 0.445 and I2 = 0.0%). Furthermore, there are statistically significant association between overall survival of NSCLC patients and the expression of Notch signaling ligand DLL3 and target gene HES1. Our meta-analysis supports that Notch signaling is a valuable bio-marker to predict progression and targeting Notch signaling could benefit subpopulation of NSCLC patients.
A method to determine the duration of the eclipse phase for in vitro infection with a highly pathogenic SHIV strain
Authors: Kakizoe Yusuke , Nakaoka Shinji , Beauchemin Catherine A. A. , Morita Satoru , Mori Hiromi , Igarashi Tatsuhiko , Aihara Kazuyuki , Miura Tomoyuki , Iwami Shingo 
Published: May 2015

AbstractThe time elapsed between successful cell infection and the start of virus production is called the eclipse phase. Its duration is specific to each virus strain and, along with an effective virus production rate, plays a key role in infection kinetics. How the eclipse phase varies amongst cells infected with the same virus strain and therefore how best to mathematically represent its duration is not clear. Most mathematical models either neglect this phase or assume it is exponentially distributed, such that at least some if not all cells can produce virus immediately upon infection. Biologically, this is unrealistic (one must allow for the translation, transcription, export, etc. to take place), but could be appropriate if the duration of the eclipse phase is negligible on the time-scale of the infection. If it is not, however, ignoring this delay affects the accuracy of the mathematical model, its parameter estimates and predictions. Here, we introduce a new approach, consisting in a carefully designed experiment and simple analytical expressions, to determine the duration and distribution of the eclipse phase in vitro. We find that the eclipse phase of SHIV-KS661 lasts on average one day and is consistent with an Erlang distribution.
Analysis of large mutations in BARD1 in patients with breast and/or ovarian cancer: the Polish population as an example
Authors: Klonowska Katarzyna , Ratajska Magdalena , Czubak Karol , Kuzniacka Alina , Brozek Izabela , Koczkowska Magdalena , Sniadecki Marcin , Debniak Jaroslaw , Wydra Dariusz , Balut Magdalena , Stukan Maciej , Zmienko Agnieszka , Nowakowska Beata , Irminger-Finger Irmgard , Limon Janusz , Kozlowski Piotr 
Published: May 2015

AbstractOnly approximately 50% of all familial breast cancers can be explained by known genetic factors, including mutations in BRCA1 and BRCA2. One of the most extensively studied candidates for breast and/or ovarian cancer susceptibility is BARD1. Although it was suggested that large mutations may contribute substantially to the deleterious variants of BARD1, no systematic study of the large mutations in BARD1 has been performed. To further elucidate the role of large mutations in BARD1, we designed a multiplex ligation-dependent probe amplification (MLPA) assay and performed an analysis of 504 women with a familial breast and/or ovarian cancer and 313 patients with ovarian cancer. The investigation did not reveal any large mutations in the BARD1 gene. Although the analysis was not focused on identification of small mutations, we detected seven deleterious or potentially deleterious point mutations, which contribute substantially to the total number of BARD1 mutations detected so far. In conclusion, although we cannot exclude the presence of large mutations in BARD1, our study indicates that such mutations do not contribute substantially to the risk of breast and/or ovarian cancer. However, it has to be noted that our results may be specific to the Polish population.