bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low phosphate activates STOP1-ALMT1 to rapidly inhibit root cell elongation
Authors: Balzergue Coline , Dartevelle Thibault , Godon Christian , Laugier Edith , Meisrimler Claudia , Teulon Jean-Marie , Creff Audrey , Bissler Marie , Brouchoud Corinne , Hagège Agnès , Müller Jens , Chiarenza Serge , Javot Hélène , Becuwe-Linka Noëlle , David Pascale , Péret Benjamin , Delannoy Etienne , Thibaud Marie-Christine , Armengaud Jean , Abel Steffen , Pellequer Jean-Luc , Nussaume Laurent , Desnos Thierry 
Published: May 2017

AbstractEnvironmental cues profoundly modulate cell proliferation and cell elongation to inform and direct plant growth and development. External phosphate (Pi) limitation inhibits primary root growth in many plant species. However, the underlying Pi sensory mechanisms are unknown. Here we genetically uncouple two Pi sensing pathways in the root apex of Arabidopsis thaliana. First, the rapid inhibition of cell elongation in the transition zone is controlled by transcription factor STOP1, by its direct target, ALMT1, encoding a malate channel, and by ferroxidase LPR1, which together mediate Fe and peroxidase-dependent cell wall stiffening. Second, during the subsequent slow inhibition of cell proliferation in the apical meristem, which is mediated by LPR1-dependent, but largely STOP1–ALMT1-independent, Fe and callose accumulate in the stem cell niche, leading to meristem reduction. Our work uncovers STOP1 and ALMT1 as a signalling pathway of low Pi availability and exuded malate as an unexpected apoplastic inhibitor of root cell wall expansion.
Probing nanofriction and Aubry-type signatures in a finite self-organized system
Authors: Kiethe J. , Nigmatullin R. , Kalincev D. , Schmirander T. , Mehlstäubler T. E. 
Published: May 2017

AbstractFriction in ordered atomistic layers plays a central role in various nanoscale systems ranging from nanomachines to biological systems. It governs transport properties, wear and dissipation. Defects and incommensurate lattice constants markedly change these properties. Recently, experimental systems have become accessible to probe the dynamics of nanofriction. Here, we present a model system consisting of laser-cooled ions in which nanofriction and transport processes in self-organized systems with back action can be studied with atomic resolution. We show that in a system with local defects resulting in incommensurate layers, there is a transition from sticking to sliding with Aubry-type signatures. We demonstrate spectroscopic measurements of the soft vibrational mode driving this transition and a measurement of the order parameter. We show numerically that both exhibit critical scaling near the transition point. Our studies demonstrate a simple, well-controlled system in which friction in self-organized structures can be studied from classical- to quantum-regimes.
Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour microenvironment
Authors: Kim Kyun-Do , Bae Seyeon , Capece Tara , Nedelkovska Hristina , de Rubio Rafael G. , Smrcka Alan V. , Jun Chang-Duk , Jung Woojin , Park Byeonghak , Kim Tae-il , Kim Minsoo 
Published: May 2017

AbstractAdoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4+CD25+Foxp3+regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca2+response. Highly selective optical control of Ca2+signalling in adoptively transferred CTLs enhances T cell activation and IFN-γ productionin vitro, leading to a significant reduction in tumour growth in mice. Altogether, our findings indicate that the targeted optogenetic stimulation of intracellular Ca2+signal allows for the remote control of cytotoxic effector functions of adoptively transferred T cells with outstanding spatial resolution by boosting T cell immune responses at the tumour sites.
In vitro evolution of an influenza broadly neutralizing antibody is modulated by hemagglutinin receptor specificity
Authors: Wu Nicholas C. , Grande Geramie , Turner Hannah L. , Ward Andrew B. , Xie Jia , Lerner Richard A. , Wilson Ian A. 
Published: May 2017

AbstractThe relatively recent discovery and characterization of human broadly neutralizing antibodies (bnAbs) against influenza virus provide valuable insights into antiviral and vaccine development. However, the factors that influence the evolution of high-affinity bnAbs remain elusive. We therefore explore the functional sequence space of bnAb C05, which targets the receptor-binding site (RBS) of influenza haemagglutinin (HA) via a long CDR H3. We combine saturation mutagenesis with yeast display to enrich for C05 variants of CDR H3 that bind to H1 and H3 HAs. The C05 variants evolve up to 20-fold higher affinity but increase specificity to each HA subtype used in the selection. Structural analysis reveals that the fine specificity is strongly influenced by a highly conserved substitution that regulates receptor binding in different subtypes. Overall, this study suggests that subtle natural variations in the HA RBS between subtypes and species may differentially influence the evolution of high-affinity bnAbs.
Absorptive pinhole collimators for ballistic Dirac fermions in graphene
Authors: Barnard Arthur W. , Hughes Alex , Sharpe Aaron L. , Watanabe Kenji , Taniguchi Takashi , Goldhaber-Gordon David 
Published: May 2017

AbstractBallistic electrons in solids can have mean free paths far larger than the smallest features patterned by lithography. This has allowed development and study of solid-state electron-optical devices such as beam splitters and quantum point contacts, which have informed our understanding of electron flow and interactions. Recently, high-mobility graphene has emerged as an ideal two-dimensional semimetal that hosts unique chiral electron-optical effects due to its honeycomb crystalline lattice. However, this chiral transport prevents the simple use of electrostatic gates to define electron-optical devices in graphene. Here we present a method of creating highly collimated electron beams in graphene based on collinear pairs of slits, with absorptive sidewalls between the slits. By this method, we achieve beams with angular width 18° or narrower, and transmission matching classical ballistic predictions.
Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins
Authors: Kang Hyeog , Oka Shinichi , Lee Duck-Yeon , Park Junhong , Aponte Angel M. , Jung Young-Sang , Bitterman Jacob , Zhai Peiyong , He Yi , Kooshapur Hamed , Ghirlando Rodolfo , Tjandra Nico , Lee Sean B. , Kim Myung K. , Sadoshima Junichi , Chung Jay H. 
Published: May 2017

AbstractSirt1 is an NAD+-dependent protein deacetylase that regulates many physiological functions, including stress resistance, adipogenesis, cell senescence and energy production. Sirt1 can be activated by energy deprivation, but the mechanism is poorly understood. Here, we report that Sirt1 is negatively regulated by ATP, which binds to the C-terminal domain (CTD) of Sirt1. ATP suppresses Sirt1 activity by impairing the CTD’s ability to bind to the deacetylase domain as well as its ability to function as the substrate recruitment site. ATP, but not NAD+, causes a conformational shift to a less compact structure. Mutations that prevent ATP binding increase Sirt1’s ability to promote stress resistance and inhibit adipogenesis under high-ATP conditions. Interestingly, the CTD can be attached to other proteins, thereby converting them into energy-regulated proteins. These discoveries provide insight into how extreme energy deprivation can impact Sirt1 activity and underscore the complex nature of Sirt1 structure and regulation.
The stabilizing effect of an oligomeric proanthocyanidin on red blood cell membrane structure of poorly controlled Type II diabetes
Authors: Visser J , van Staden P J , Soma P , Buys A V , Pretorius E 
Published: May 2017

AbstractType II diabetes (T2D) is a pandemic characterized by pathological circulating inflammatory markers, high-glucose levels and oxidative stress. The hematological system is especially vulnerable to these aberrant circulating molecules, and erythrocytes (RBCs) show aberrant rheology properties, owing to the direct contact with these molecules. Pathological levels of circulating inflammatory markers in T2D therefore have a direct effect on the molecular and cellular structure of RBCs. Previous research has suggested that antioxidants may reduce oxidative stress that results from the pathological inflammatory markers. Particularly, polyphenol antioxidants like oligomeric proanthocyanidins (OPCs) may act as a hydroxyl mopping agent, and may have a positive effect on the deformability and membrane protein structure of RBCs from T2D. In this paper, we look at the effect of one such agent,Pinus massonianabark extract (standardized to 95% oligomeric proanthicyanidins), on the RBC membrane structures and RBC shape changes of T2D, after laboratory exposure at physiological levels. Our methods of choice were atomic force microscopy and scanning electron microscopy to study RBC elasticity and ultrastructure. Results showed that in our hands, this OPC could change both the eryptotic nature of the RBCs, as viewed with scanning electron microscopy, as well as the elasticity. We found a significant difference in variation between the elasticity measurement values between the RBCs before and after OPC exposure (P-value <0.0001). In conclusion, the data from both these techniques therefore suggest that OPC usage might contribute to the improvement of RBC functioning.
Molecular signaling in multiple myeloma: association of RAS/RAF mutations and MEK/ERK pathway activation
Authors: Xu J , Pfarr N , Endris V , Mai E K , Md Hanafiah N H , Lehners N , Penzel R , Weichert W , Ho A D , Schirmacher P , Goldschmidt H , Andrulis M , Raab M S 
Published: May 2017

AbstractMultiple myeloma (MM) is a plasma cell malignancy that is still considered to be incurable in most cases. A dominant mutation cluster has been identified in RAS/RAF genes, emphasizing the potential significance of RAS/RAF/MEK/ERK signaling as a therapeutic target. As yet, however, the clinical relevance of this finding is unclear as clinical responses to MEK inhibition in RAS-mutant MM have been mixed. We therefore assessed RAS/RAF mutation status and MEK/ERK pathway activation by both targeted sequencing and phospho-ERK immunohistochemistry in 180 tissue biopsies from 103 patients with newly diagnosed MM (NDMM) and 77 patients with relapsed/refractory MM (rrMM). We found a significant enrichment of RAS/BRAF mutations in rrMM compared to NDMM (P=0.011), which was mainly due to an increase of NRAS mutations (P=0.010). As expected, BRAF mutations were significantly associated with activated downstream signaling. However, only KRAS and not NRAS mutations were associated with pathway activation compared to RAS/BRAFwt (P=0.030). More specifically, only KRASG12D and BRAFV600E were consistently associated with ERK activation (P<0.001 and P=0.006, respectively). Taken together, these results suggest the need for a more specific stratification strategy consisting of both confirmation of protein-level pathway activation as well as detailed RAS/RAF mutation status to allow for a more precise and more effective application of targeted therapies, for example, with BRAF/MEK inhibitors in MM.
The contribution of an asthma diagnostic consultation service in obtaining an accurate asthma diagnosis for primary care patients: results of a real-life study
Authors: Gillis R. M. E. , van Litsenburg W. , van Balkom R. H. , Muris J. W. , Smeenk F. W. 
Published: May 2017

AbstractPrevious studies showed that general practitioners have problems in diagnosing asthma accurately, resulting in both under and overdiagnosis. To support general practitioners in their diagnostic process, an asthma diagnostic consultation service was set up. We evaluated the performance of this asthma diagnostic consultation service by analysing the (dis)concordance between the general practitioners working hypotheses and the asthma diagnostic consultation service diagnoses and possible consequences this had on the patients’ pharmacotherapy. In total 659 patients were included in this study. At this service the patients’ medical history was taken and a physical examination and a histamine challenge test were carried out. We compared the general practitioners working hypotheses with the asthma diagnostic consultation service diagnoses and the change in medication that was incurred. In 52% (n = 340) an asthma diagnosis was excluded. The diagnosis was confirmed in 42% (n = 275). Furthermore, chronic rhinitis was diagnosed in 40% (n = 261) of the patients whereas this was noted in 25% (n = 163) by their general practitioner. The adjusted diagnosis resulted in a change of medication for more than half of all patients. In 10% (n = 63) medication was started because of a new asthma diagnosis. The ‘one-stop-shop’ principle was met with 53% of patients and 91% (n = 599) were referred back to their general practitioner, mostly within 6 months. Only 6% (n = 41) remained under control of the asthma diagnostic consultation service because of severe unstable asthma. In conclusion, the asthma diagnostic consultation service helped general practitioners significantly in setting accurate diagnoses for their patients with an asthma hypothesis. This may contribute to diminish the problem of over and underdiagnosis and may result in more appropriate treatment regimens.
Delineation of B-cell Epitopes of Salmonella enterica serovar Typhi Hemolysin E: Potential antibody therapeutic target
Authors: Chin Chai Fung , Lai Jing Yi , Choong Yee Siew , Anthony Amy Amilda , Ismail Asma , Lim Theam Soon 
Published: May 2017

AbstractHemolysin E (HlyE) is an immunogenic novel pore-forming toxin involved in the pathogenesis of typhoid fever. Thus, mapping of B-cell epitopes of Salmonella enterica serovar Typhi (S. Typhi) is critical to identify key immunogenic regions of HlyE. A random 20-mer peptide library was used for biopanning with enriched anti-HlyE polyclonal antibodies from typhoid patient sera. Bioinformatic tools were used to refine, analyze and map the enriched peptide sequences against the protein to identify the epitopes. The analysis identified both linear and conformational epitopes on the HlyE protein. The predicted linear GAAAGIVAG and conformational epitope PYSQESVLSADSQNQK were further validated against the pooled sera. The identified epitopes were then used to isolate epitope specific monoclonal antibodies by antibody phage display. Monoclonal scFv antibodies were enriched for both linear and conformational epitopes. Molecular docking was performed to elucidate the antigen-antibody interaction of the monoclonal antibodies against the epitopes on the HlyE monomer and oligomer structure. An in-depth view of the mechanistic and positional characteristics of the antibodies and epitope for HlyE was successfully accomplished by a combination of phage display and bioinformatic analysis. The predicted function and structure of the antibodies highlights the possibility of utilizing the antibodies as neutralizing agents for typhoid fever.
Chemical Structure of the Lipid A component of Pseudomonas sp. strain PAMC 28618 from Thawing Permafrost in Relation to Pathogenicity
Authors: Park Han-Gyu , Sathiyanarayanan Ganesan , Hwang Cheol-Hwan , Ann Da-Hee , Kim Jung-Ho , Bang Geul , Jang Kyoung-Soon , Ryu Hee Wook , Lee Yoo Kyung , Yang Yung-Hun , Kim Yun-Gon 
Published: May 2017

AbstractClimate change causes permafrost thawing, and we are confronted with the unpredictable risk of newly discovered permafrost microbes that have disease-causing capabilities. Here, we first characterized the detailed chemical structure of the lipid A moiety from a Pseudomonas species that was isolated from thawing arctic permafrost using MALDI-based mass spectrometric approaches (i.e., MALDI-TOF MS and MALDI-QIT-TOF MSn). The MALDI multi-stage mass spectrometry (MS) analysis of lipid A extracted from the Pseudomonas sp. strain PAMC 28618 demonstrated that the hexaacyl lipid A ([M−H]− at m/z 1616.5) contains a glucosamine (GlcN) disaccharide backbone, two phosphates, four main acyl chains and two branched acyl chains. Moreover, the lipid A molecule–based structural activity relationship with other terrestrial Gram-negative bacteria indicated that strain PAMC 28618 has an identical lipid A structure with the mesophilic Pseudomonas cichorii which can cause rot disease in endive (Cichorium endivia) and that their bacterial toxicities were equivalent. Therefore, the overall lipid A validation process provides a general strategy for characterizing bacteria that have been isolated from arctic permafrost and analyzing their respective pathogenicities.
Characterization of TRPA channels in the starfish Patiria pectinifera: involvement of thermally activated TRPA1 in thermotaxis in marine planktonic larvae
Authors: Saito Shigeru , Hamanaka Gen , Kawai Narudo , Furukawa Ryohei , Gojobori Jun , Tominaga Makoto , Kaneko Hiroyuki , Satta Yoko 
Published: May 2017

AbstractThe vast majority of marine invertebrates spend their larval period as pelagic plankton and are exposed to various environmental cues. Here we investigated the thermotaxis behaviors of the bipinnaria larvae of the starfish, Patiria pectinifera, in association with TRPA ion channels that serve as thermal receptors in various animal species. Using a newly developed thermotaxis assay system, we observed that P. pectinifera larvae displayed positive thermotaxis toward high temperatures, including toward temperatures high enough to cause death. In parallel, we identified two TRPA genes, termed PpTRPA1 and PpTRPA basal, from this species. We examined the phylogenetic position, spatial expression, and channel properties of each PpTRPA. Our results revealed the following: (1) The two genes diverged early in animal evolution; (2) PpTRPA1 and PpTRPA basal are expressed in the ciliary band and posterior digestive tract of the larval body, respectively; and (3) PpTRPA1 is activated by heat stimulation as well as by known TRPA1 agonists. Moreover, knockdown and rescue experiments demonstrated that PpTRPA1 is involved in positive thermotaxis in P. pectinifera larvae. This is the first report to reveal that TRPA1 channels regulate the behavioral response of a marine invertebrate to temperature changes during its planktonic larval period.
Health benefit of vegetable/fruit juice-based diet: Role of microbiome
Authors: Henning Susanne M. , Yang Jieping , Shao Paul , Lee Ru-Po , Huang Jianjun , Ly Austin , Hsu Mark , Lu Qing-Yi , Thames Gail , Heber David , Li Zhaoping 
Published: May 2017

AbstractThe gut microbiota is an important contributor to human health. Vegetable/fruit juices provide polyphenols, oligosaccharides, fiber and nitrate (beet juice), which may induce a prebiotic-like effect. Juice-based diets are becoming popular. However, there is a lack of scientific evidence of their health benefits. It was our hypothesis that changes in the intestinal microbiota induced by a juice-based diet play an important role in their health benefits. Twenty healthy adults consumed only vegetable/fruit juices for 3 days followed by 14 days of customary diet. On day 4 we observed a significant decrease in weight and body mass index (p = 2.0E−05), which was maintained until day 17 (p = 3.0E−04). On day 4 the proportion of the phylum Firmicutes and Proteobacteria in stool was significantly decreased and Bacteroidetes and Cyanobacteria was increased compared to baseline and was partially reversed on day 17. On day 4 plasma and urine nitric oxide was increased by 244 ± 89% and 450 ± 360%, respectively, and urinary lipid peroxidation marker malondialdehyde was decreased by 32 ± 21% compared to baseline. General well-being score was increased at the end of the study. In summary a 3-day juice-based diet altered the intestinal microbiota associated with weight loss, increase in the vasodilator NO, and decrease in lipid oxidation.
EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons
Authors: Burk Katja , Murdoch John D. , Freytag Siona , Koenig Melanie , Bharat Vinita , Markworth Ronja , Burkhardt Susanne , Fischer Andre , Dean Camin 
Published: May 2017

AbstractThe sorting of activated receptors into distinct endosomal compartments is essential to activate specific signaling cascades and cellular events including growth and survival. However, the proteins involved in this sorting are not well understood. We discovered a novel role of EndophilinAs in sorting of activated BDNF-TrkB receptors into late endosomal compartments. Mice lacking all three EndophilinAs accumulate Rab7-positive late endosomes. Moreover, EndophilinAs are differentially localized to, co-traffic with, and tubulate, distinct endosomal compartments: In response to BDNF, EndophilinA2 is recruited to both early and late endosomes, EndophilinA3 is recruited to Lamp1-positive late endosomes, and co-trafficks with Rab5 and Rab7 in both the presence and absence of BDNF, while EndophilinA1 colocalizes at lower levels with endosomes. The absence of all three EndophilinAs caused TrkB to accumulate in EEA1 and Rab7-positive endosomes, and impaired BDNF-TrkB-dependent survival signaling cascades. In addition, EndophilinA triple knockout neurons exhibited increased cell death which could not be rescued by exogenous BDNF, in a neurotrophin-dependent survival assay. Thus, EndophilinAs differentially regulate activated receptor sorting via distinct endosomal compartments to promote BDNF-dependent cell survival.
Thioflavin T fluoresces as excimer in highly concentrated aqueous solutions and as monomer being incorporated in amyloid fibrils
Authors: Sulatskaya Anna I. , Lavysh Andrey V. , Maskevich Alexander A. , Kuznetsova Irina M. , Turoverov Konstantin K. 
Published: May 2017

AbstractFluorescence of thioflavin T (ThT) is a proven tool for amyloid fibrils study. The correct model of ThT binding to fibrils is crucial to clarify amyloid fibrils structure and mechanism of their formation. Although there are convincing evidences that ThT has molecular rotor nature, implying it’s binding to fibrils in monomer form, speculations concerning ThT binding to fibrils in aggregated forms appear in literature so far. The elaborated approach for fluorescence intensity correction on the inner filter effects applied to ThT aqueous solutions with a wide range of concentration allowed characterizing ThT excimers fluorescence and showing its difference from that of ThT bound to fibrils. Obtained results experimentally prove the monomer model of ThT binding to amyloid fibrils and demonstrate wide capacity of the used approach in the spectroscopy of other fluorescent dyes for examination of concentration self-quenching and deformation of fluorescence spectra, dye molecules interaction, dimers and excimers formation.