bluuebunny/crossref_metadata_2025_split huggingface dataset:
NFATc1 controls the cytotoxicity of CD8+ T cells
Authors: Klein-Hessling Stefan , Muhammad Khalid , Klein Matthias , Pusch Tobias , Rudolf Ronald , Flöter Jessica , Qureischi Musga , Beilhack Andreas , Vaeth Martin , Kummerow Carsten , Backes Christian , Schoppmeyer Rouven , Hahn Ulrike , Hoth Markus , Bopp Tobias , Berberich-Siebelt Friederike , Patra Amiya , Avots Andris , Müller Nora , Schulze Almut , Serfling Edgar 
Published: September 2017

AbstractCytotoxic T lymphocytes are effector CD8+ T cells that eradicate infected and malignant cells. Here we show that the transcription factor NFATc1 controls the cytotoxicity of mouse cytotoxic T lymphocytes. Activation of Nfatc1
−/−
cytotoxic T lymphocytes showed a defective cytoskeleton organization and recruitment of cytosolic organelles to immunological synapses. These cells have reduced cytotoxicity against tumor cells, and mice with NFATc1-deficient T cells are defective in controlling Listeria infection. Transcriptome analysis shows diminished RNA levels of numerous genes in Nfatc1
−/−
CD8+ T cells, including Tbx21, Gzmb and genes encoding cytokines and chemokines, and genes controlling glycolysis. Nfatc1
−/−
, but not Nfatc2
−/−
CD8+ T cells have an impaired metabolic switch to glycolysis, which can be restored by IL-2. Genome-wide ChIP-seq shows that NFATc1 binds many genes that control cytotoxic T lymphocyte activity. Together these data indicate that NFATc1 is an important regulator of cytotoxic T lymphocyte effector functions.
Video intervention increases participation of black breast cancer patients in therapeutic trials
Authors: Robinson Brandi N. , Newman Antoinette F. , Tefera Eshetu , Herbolsheimer Pia , Nunes Raquel , Gallagher Christopher , Randolph-Jackson Pamela , Omogbehin Adedamola , Dilawari Asma , Pohlmann Paula R. , Mohebtash Mahsa , Lee Young , Ottaviano Yvonne , Mohapatra Avani , Lynce Filipa , Brown Richard , Mete Mihriye , Swain Sandra M. 
Published: September 2017

AbstractThere is a striking racial and ethnic disparity in incidence and mortality of cancer yet minorities remain markedly underrepresented in clinical trials. This pilot study set out to determine the impact of a 15-min culturally tailored educational video on three outcomes relating to clinical trials: likely participation, attitudes (assessed based on six barriers), and actual enrollment. Breast cancer patients with Stage I-III, if diagnosed within previous 6 months, or metastatic disease who self-identified as black or African American were invited to participate. The primary outcome measure was the decision to participate in a therapeutic clinical trial after the intervention. Patients’ intention to enroll on a therapeutic clinical trial and the change in attitudes toward clinical trials were measured by the previously developed Attitudes and Intention to Enroll in Therapeutic Clinical Trials (AIET) questionnaire. Of the 200 patients that participated, 39 (19.5%) patients signed consent to participate in a therapeutic clinical trial; 27 (13.5%) patients enrolled, resulting in a 7.5% increase from our baseline comparison of 6% clinical trial enrollment rate in black cancer patients (p < .001). Pre-test versus post-test assessment demonstrated the proportion of patients expressing likelihood to enroll in a therapeutic trial following the intervention increased by 14% (p < .001). Among 31 AIET items, 25 (81%) showed statistically significant and positive change post-intervention. The findings suggest the promising utility of a culturally tailored video intervention for improving black patients’ attitudes regarding clinical trial participation and resultant enrollment. Future efforts should continue to target facilitators of population-specific recruitment, enrollment, and retention in therapeutic and non-therapeutic clinical trials.
Sample space reducing cascading processes produce the full spectrum of scaling exponents
Authors: Corominas-Murtra Bernat , Hanel Rudolf , Thurner Stefan 
Published: September 2017

AbstractSample Space Reducing (SSR) processes are simple stochastic processes that offer a new route to understand scaling in path-dependent processes. Here we define a cascading process that generalises the recently defined SSR processes and is able to produce power laws with arbitrary exponents. We demonstrate analytically that the frequency distributions of states are power laws with exponents that coincide with the multiplication parameter of the cascading process. In addition, we show that imposing energy conservation in SSR cascades allows us to recover Fermi’s classic result on the energy spectrum of cosmic rays, with the universal exponent −2, which is independent of the multiplication parameter of the cascade. Applications of the proposed process include fragmentation processes or directed cascading diffusion on networks, such as rumour or epidemic spreading.
Onset of disorder and protein aggregation due to oxidation-induced intermolecular disulfide bonds: case study of RRM2 domain from TDP-43
Authors: Rabdano Sevastyan O. , Izmailov Sergei A. , Luzik Dmitrii A. , Groves Adam , Podkorytov Ivan S. , Skrynnikov Nikolai R. 
Published: September 2017

AbstractWe have investigated the behavior of second RNA-recognition motif (RRM2) of neuropathological protein TDP43 under the effect of oxidative stress as modeledin vitro. Toward this end we have used the specially adapted version of H/D exchange experiment, NMR relaxation and diffusion measurements, dynamic light scattering, controlled proteolysis, gel electrophoresis, site-directed mutagenesis and microsecond MD simulations. Under oxidizing conditions RRM2 forms disulfide-bonded dimers that experience unfolding and then assemble into aggregate particles (APs). These particles are strongly disordered, highly inhomogeneous and susceptible to proteolysis; some of them withstand the dithiothreitol treatment. They can recruit/release monomeric RRM2 through thiol-disulfide exchange reactions. By using a combination of dynamic light scattering and NMR diffusion data we were able to approximate the size distribution function for the APs. The key to the observed aggregation behavior is the diminished ability of disulfide-bonded RRM2 dimers to refold and their increased propensity to misfold, which makes them vulnerable to large thermal fluctuations. The emerging picture provides detailed insight on how oxidative stress can contribute to neurodegenerative disease, with unfolding, aggregation, and proteolytic cleavage as different facets of the process.
Effects of purified or plant-produced Cry proteins on Drosophila melanogaster (Diptera: Drosophilidae) larvae
Authors: Haller Simone , Romeis Jörg , Meissle Michael 
Published: September 2017

AbstractAlthough genetically engineered crops producing insecticidal Cry proteins from Bacillus thuringiensis (Bt) are grown worldwide, few studies cover effects of Bt crops or Cry proteins on dipteran species in an agricultural context. We tested the toxicity of six purified Cry proteins and of Bt cotton and Bt maize tissue on Drosophila melanogaster (Diptera: Drosophilidae) as a surrogate for decomposing Diptera. ELISA confirmed the presence of Cry proteins in plant material, artificial diet, and fly larvae, and concentrations were estimated. Median concentrations in emerging adult flies were below the limit of detection. Bioactivity of purified Cry proteins in the diet was confirmed by sensitive species assays using Heliothis virescens (Lepidoptera: Noctuidae). Purified Cry1Ab, Cry1Ac, Cry1B, Cry1C, Cry1F, or Cry2Aa, or leaf material from stacked Bt cotton (Bollgard II producing Cry1Ac and Cry2Ab) or Bt maize (SmartStax producing Cry1A.105, Cry1Fa2, Cry2Ab2, Cry3Bb1, Cry34Ab1 and Cry35Ab1) had no consistent effects on D. melanogaster survival, developmental time, adult body mass or morphometrics. However, D. melanogaster showed longer developmental time and smaller wing size when fed with cotton leaves from plants infested with H. virescens caterpillars compared to flies fed with leaves from uninfested plants, while no such effects were obvious for maize.
Intrinsic property of phenylalanine to trigger protein aggregation and hemolysis has a direct relevance to phenylketonuria
Authors: Anand Bibin G. , Dubey Kriti , Shekhawat Dolat S. , Kar Karunakar 
Published: September 2017

AbstractExcess accumulation of phenylalanine is the characteristic of untreated Phenylketonuria (PKU), a well-known genetic abnormality, which triggers several neurological, physical and developmental severities. However, the fundamental mechanism behind the origin of such diverse health problems, particularly the issue of how they are related to the build-up of phenylalanine molecules in the body, is largely unknown. Here, we show cross-seeding ability of phenylalanine fibrils that can effectively initiate an aggregation process in proteins under physiological conditions, converting native protein structures to β-sheet assembly. The resultant fibrils were found to cause severe hemolysis, yielding a plethora of deformed erythrocytes that is highly relevant to phenylketonuria. Unique arrangement of zwitterionic phenylalanine molecules in their amyloid-like higher order entities is predicted to promote both hydrophobic and electrostatic interaction, sufficient enough to trap proteins and to preferentially interact with the membrane components of RBCs. Since the prevalence of hemolysis and amyloid related psychoneurological severities are mostly observed in PKU patients, we propose that the inherent property of phenylalanine fibrils to trigger hemolysis and to induce protein aggregation may have direct relevance to the disease mechanism of PKU.
Complex dynamics at the nanoscale in simple biomembranes
Authors: Sarangi Nirod Kumar , Ayappa K. G. , Basu Jaydeep Kumar 
Published: September 2017

AbstractNature is known to engineer complex compositional and dynamical platforms in biological membranes. Understanding this complex landscape requires techniques to simultaneously detect membrane re-organization and dynamics at the nanoscale. Using super-resolution stimulated emission depletion (STED) microscopy coupled with fluorescence correlation spectroscopy (FCS), we reveal direct experimental evidence of dynamic heterogeneity at the nanoscale in binary phospholipid-cholesterol bilayers. Domain formation on the length scale of ~200–600 nm due to local cholesterol compositional heterogeneity is found to be more prominent at high cholesterol content giving rise to distinct intra-domain lipid dynamics. STED-FCS reveals unique dynamical crossover phenomena at length scales of ~100–150 nm within each of these macroscopic regions. The extent of dynamic heterogeneity due to intra-domain hindered lipid diffusion as reflected from the crossover length scale, is driven by cholesterol packing and organization, uniquely influenced by phospholipid type. These results on simple binary model bilayer systems provide novel insights into pathways leading to the emergence of complex nanodomain substructures with implications for a wide variety of membrane mediated cellular events.
The quantum-optics Hamiltonian in the Multipolar gauge
Authors: Rousseau Emmanuel , Felbacq Didier 
Published: September 2017

AbstractThis article deals with the fundamental problem of light-matter interaction in the quantum theory. Although it is described through the vector potential in quantum electrodynamics, it is believed by some that a hamiltonian involving only the electric and the magnetic fields is preferable. In the literature this hamiltonian is known as the Power-Zienau-Woolley hamiltonian. We question its validity and show that it is not equivalent to the minimal-coupling hamiltonian. In this article, we show that these two hamiltonians are not connected through a gauge transformation. We find that the gauge is not fixed in the Power-Zienau-Woolley hamiltonian. The interaction term is written in one gauge whereas the rest of the hamiltonian is written in another gauge. The Power-Zienau-Woolley hamiltonian and the minimal-coupling one are related through a unitary transformation that does not fulfill the gauge fixing constraints. Consequently, they predict different physical results. In this letter, we provide the correct quantum theory in the multipolar gauge with a hamiltonian involving only the physical fields.
Preparation of porous Fe2O3 nanorods-reduced graphene oxide nanohybrids and their excellent microwave absorption properties
Authors: Hu Qi , Qi Xiaosi , Cai Hongbo , Xie Ren , Long Liu , Bai Zhongchen , Jiang Yang , Qin Shuijie , Zhong Wei , Du Youwei 
Published: September 2017

AbstractIn this paper, α-Fe2O3 nanoparticles (NPs)-reduced graphene oxide (RGO), α-FeOOH nanorods (NRs)-RGO and porous α-Fe2O3 NRs-RGO could be selectively synthesized by hydrothermal method. The investigations indicated that the obtained α-Fe2O3 NPs, α-FeOOH NRs and porous α-Fe2O3 NRs were either attached on the surface of RGO sheets or coated uniformly by the RGO sheets. And the as-prepared nanohybrids exhibited excellent microwave absorption performance, which was proved to be ascribed to the quarter-wavelength matching model. The optimum reflection loss (RL) values for α-Fe2O3 NPs-RGO, α-FeOOH NRs-RGO and porous α-Fe2O3 NRs-RGO were ca. −32.3, −37.4 and −71.4 dB, respectively. Moreover, compared to the obtained α-Fe2O3 NPs-RGO and α-FeOOH NRs-RGO, the as-prepared porous α-Fe2O3 NRs-RGO nanohybrids exhibited enhanced microwave absorption properties because of their special structure and synergetic effect. The possible enhanced microwave absorption mechanisms were discussed in details. Our results confirmed that the geometrical morphology had a great influence on their microwave absorption properties, which provided a promising approach to exploit high performance microwave absorbing materials.
Separability of neural responses to standardised mechanical stimulation of limbs
Authors: Brunton Emma , Blau Christoph W. , Nazarpour Kianoush 
Published: September 2017

AbstractConsiderable scientific and technological efforts are currently being made towards the development of neural prostheses. Understanding how the peripheral nervous system responds to electro-mechanical stimulation of the limb, will help to inform the design of prostheses that can restore function or accelerate recovery from injury to the sensory motor system. However, due to differences in experimental protocols, it is difficult, if not impossible, to make meaningful comparisons between different peripheral nerve interfaces. Therefore, we developed a low-cost electronic system to standardise the mechanical stimulation of a rat’s hindpaw. Three types of mechanical stimulations, namely, proprioception, touch and nociception were delivered to the limb and the electroneurogram signals were recorded simultaneously from the sciatic nerve with a 16-contact cuff electrode. For the first time, results indicate separability of neural responses according to stimulus type as well as intensity. Statistical analysis reveal that cuff contacts placed circumferentially, rather than longitudinally, are more likely to lead to higher classification rates. This flexible setup may be readily adapted for systematic comparison of various electrodes and mechanical stimuli in rodents. Hence, we have made its electro-mechanical design and computer programme available online
Cortisol overproduction results from DNA methylation of CYP11B1 in hypercortisolemia
Authors: Kometani Mitsuhiro , Yoneda Takashi , Demura Masashi , Koide Hiroshi , Nishimoto Koshiro , Mukai Kuniaki , Gomez-Sanchez Celso E. , Akagi Tadayuki , Yokota Takashi , Horike Shin-ichi , Karashima Shigehiro , Miyamori Isamu , Yamagishi Masakazu , Takeda Yoshiyu 
Published: September 2017

AbstractAdrenocortical hormone excess, due to primary aldosteronism (PA) or hypercortisolemia, causes hypertension and cardiovascular complications. In PA, hypomethylation of aldosterone synthase (CYP11B2) is associated with aldosterone overproduction. However, in hypercortisolemia, the role of DNA methylation of 11β-hydroxylase (CYP11B1), which catalyzes cortisol biosynthesis and is highly homologous to CYP11B2, is unclear. The aims of our study were to determine whether the CYP11B1 expression was regulated through DNA methylation in hypercortisolemia with cortisol-producing adenoma (CPA), and to investigate a possible relationship between DNA methylation and somatic mutations identified in CPA. Methylation analysis showed that the CYP11B1 promoter was significantly less methylated in CPA than in adjacent unaffected adrenal tissue and white blood cells. Furthermore, in CPA with somatic mutations in either the catalytic subunit of protein kinase A (PRKACA) or the guanine nucleotide-binding protein subunit alpha (GNAS) gene, the CYP11B1 promoter was significantly hypomethylated. In addition, DNA methylation reduced CYP11B1 promoter activity using a reporter assay. Our study results suggest that DNA methylation at the CYP11B1 promoter plays a role in the regulation of CYP11B1 expression and cortisol production in CPA, and that somatic mutations associated with CPA reduce DNA methylation at the CYP11B1 promoter.
Thrombin-derived host defence peptide modulates neutrophil rolling and migration in vitro and functional response in vivo
Authors: Lim Chun Hwee , Puthia Manoj , Butrym Marta , Tay Hui Min , Lee Michelle Zi Yi , Hou Han Wei , Schmidtchen Artur 
Published: September 2017

AbstractHost defence peptides (HDPs) derived from the C-terminus of thrombin are proteolytically generated by enzymes released during inflammation and wounding. In this work, we studied the effects of the prototypic peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), on neutrophil functions.In vitro, GKY25 was shown to decrease LPS-induced neutrophil activation. In addition, the peptide induced CD62L shedding on neutrophils without inducing their activation. Correspondingly, GKY25-treated neutrophils showed reduced attachment and rolling behaviour on surfaces coated with the CD62L ligand E-selectin. The GKY25-treated neutrophils also displayed a dampened chemotactic response against the chemokine IL-8. Furthermore,in vivo, mice treated with GKY25 exhibited a reduced local ROS response against LPS. Taken together, our results show that GKY25 can modulate neutrophil functionsin vitroandin vivo.
Recycling of a selectable marker with a self-excisable plasmid in Pichia pastoris
Authors: Li Cheng , Lin Ying , Zheng Xueyun , Yuan Qingyan , Pang Nuo , Liao Xihao , Huang Yuanyuan , Zhang Xinying , Liang Shuli 
Published: September 2017

AbstractPichia pastorisis a widely used heterologous protein production workhorse. However, with its multiple genetic modifications to solve bottlenecks for heterologous protein productivity,P. pastorislacks selectable markers. Existing selectable marker recycling plasmids have drawbacks (e.g., slow growth and conditional lethality). Here, zeocin-resistance marker recycling vectors were constructed using the Cre/loxPrecombination system. The vectors were used to (i) knock in heterologous phytase, xylanase and lipase expression cassettes, (ii) increase the phytase, xylanase and lipase gene copy number to 13, 5, and 5, respectively, with vector introduction and (iii) engineer the secretion pathway by co-overexpressing secretion helper factors (Sly1p and Sec1p) without introducing selectable markers, giving a phytase field of 0.833 g/L. The vectors allow selectable marker recycling and would be a useful tool to engineerP. pastorisfor high heterologous protein productivity.
An embryonic system to assess direct and indirect Wnt transcriptional targets
Authors: Suresh Jahnavi , Harmston Nathan , Lim Ka Keat , Kaur Prameet , Jin Helen Jingshu , Lusk Jay B. , Petretto Enrico , Tolwinski Nicholas S. 
Published: September 2017

AbstractDuring animal development, complex signals determine and organize a vast number of tissues using a very small number of signal transduction pathways. These developmental signaling pathways determine cell fates through a coordinated transcriptional response that remains poorly understood. The Wnt pathway is involved in a variety of these cellular functions, and its signals are transmitted in part through a β-catenin/TCF transcriptional complex. Here we report an in vivo Drosophila assay that can be used to distinguish between activation, de-repression and repression of transcriptional responses, separating upstream and downstream pathway activation and canonical/non-canonical Wnt signals in embryos. We find specific sets of genes downstream of both β-catenin and TCF with an additional group of genes regulated by Wnt, while the non-canonical Wnt4 regulates a separate cohort of genes. We correlate transcriptional changes with phenotypic outcomes of cell differentiation and embryo size, showing our model can be used to characterize developmental signaling compartmentalization in vivo.
Laser-Induced Linear-Field Particle Acceleration in Free Space
Authors: Wong Liang Jie , Hong Kyung-Han , Carbajo Sergio , Fallahi Arya , Piot Philippe , Soljačić Marin , Joannopoulos John D. , Kärtner Franz X. , Kaminer Ido 
Published: September 2017

AbstractLinear-field particle acceleration in free space (which is distinct from geometries like the linac that requires components in the vicinity of the particle) has been studied for over 20 years, and its ability to eventually produce high-quality, high energy multi-particle bunches has remained a subject of great interest. Arguments can certainly be made that linear-field particle acceleration in free space is very doubtful given that first-order electron-photon interactions are forbidden in free space. Nevertheless, we chose to develop an accurate and truly predictive theoretical formalism to explore this remote possibility when intense, few-cycle electromagnetic pulses are used in a computational experiment. The formalism includes exact treatment of Maxwell’s equations and exact treatment of the interaction among the multiple individual particles at near and far field. Several surprising results emerge. We find that electrons interacting with intense laser pulses in free space are capable of gaining substantial amounts of energy that scale linearly with the field amplitude. For example, 30 keV electrons (2.5% energy spread) are accelerated to 61 MeV (0.5% spread) and to 205 MeV (0.25% spread) using 250 mJ and 2.5 J lasers respectively. These findings carry important implications for our understanding of ultrafast electron-photon interactions in strong fields.
The combined effect of cigarette smoking and occupational noise exposure on hearing loss: evidence from the Dongfeng-Tongji Cohort Study
Authors: Wang Dongming , Wang Zhichao , Zhou Min , Li Wenzhen , He Meian , Zhang Xiaomin , Guo Huan , Yuan Jing , Zhan Yue , Zhang Kun , Zhou Tao , Kong Weijia , Chen Weihong 
Published: September 2017

AbstractCombined effect of cigarette smoking and occupational noise exposure on hearing loss has rarely been evaluated among Chinese population, especially among females. This cross-sectional study was conducted in 11196 participants of Dongfeng-Tongji cohort study. Smoking status was self-reported through questionnaire and occupational noise exposure was evaluated through workplace noise level and/or the job titles. Hearing loss was defined as a pure-tone mean of 25 dB or higher at 0.5, 1, 2, and 4 kHz in both ears. Compared with participants without occupational noise exposure, the risk of hearing loss was significantly higher for noise exposure duration ≥20 (OR = 1.45, 95%CI = 1.28–1.65). The association was particularly evident among individuals who were males (OR = 1.74, 95%CI = 1.45–2.08) and aged ≥ 70 (OR = 1.74, 95%CI = 1.30–2.33). Similarly, the risks increased with the increasing of pack-years in males and all age groups except for those aged <60. As to the combined effect, the hearing loss risk was highest for noise exposure duration ≥20 and pack-years ≥25 (OR = 2.41, 95%CI = 1.78–3.28), especially among males (OR = 2.42, 95%CI = 1.74–3.37) and those aged ≥70 (OR = 2.76, 95%CI = 1.36–5.60). Smoking may be an independent risk factor for hearing loss. And it may synergistically affect hearing when combined with occupational noise exposure, especially among males and older participants.