bluuebunny/crossref_metadata_2025_split huggingface dataset:
HDAC and Ku70 axis- an effective target for apoptosis induction by a new 2-cyano-3-oxo-1,9-dien glycyrrhetinic acid analogue
Authors: Gong Ping , Li Kun , Li Ying , Liu Dan , Zhao Linxiang , Jing Yongkui 
Published: May 2018

AbstractMethyl 2-cyano-3,12-dioxo-18β-olean-1,9(11)-dien-30-oate (CDODO-Me, 10d) derived from glycyrrhetinic acid and methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO-Me) derived from oleanoic acid are potent apoptosis inducers developed to clinical trials. Both compounds have high affinity for reduced glutathione (GSH), which needs to be overcome to improve their target selectivity. We generated a new 10d analogue methyl 2-cyano-3-oxo-18β-olean-1,9(11), 12-trien-30-oate (COOTO, 10e), which retains high apoptosis inducing ability, while displaying decreased affinity for GSH, and explored the acting targets. We found that it induces Noxa level, reduces c-Flip level and causes Bax/Bak activation. Silencing of either Noxa or Bak significantly attenuated apoptosis induction of 10e. We linked these events due to targeting HDAC3/HDAC6 and Ku70 axis. 10e treatment reduced the levels of HDAC3 and HDAC6 with increased DNA damage/repair marker gamma-H2AX (γ-H2AX) and acetylated Ku70. c-Flip dissociates from acetylated Ku70 undergoing degradation, while Bax dissociates from acetylated Ku70 undergoing activation. Silencing of either HDAC3 or HDAC6 enhanced 10e-induced apoptosis. We reveal a new action cascade of this category of compounds that involves targeting of HADC3/6 proteins and Ku70 acetylation.
The A/T/N biomarker scheme and patterns of brain atrophy assessed in mild cognitive impairment
Authors: Ekman Urban , Ferreira Daniel , Westman Eric 
Published: May 2018

AbstractThe objective of this study was to evaluate the A/T/N biomarker scheme in relation with brain atrophy patterns in individuals with mild cognitive impairment (MCI). Of the 154 participants with MCI, 74 progressed to AD within 36-months, and 80 remained stable. In addition, 101 cognitively healthy participants and 102 participants with AD were included. The A/T/N classification was assessed with cerebrospinal fluid markers. Each individual was rated as either positive (abnormal) or negative (normal) on each biomarker. Brain atrophy was assessed with visual ratings from magnetic resonance imaging. None of the individuals with MCI progressed to AD if they had a negative “A” biomarker in conjunction with minimal atrophy. In contrary, several individuals with MCI progressed to AD if they had a positive “A” biomarker in conjunction with minimal atrophy. Numerous individuals with MCI showed inconsistency in the neurodegeneration domain (“N”) regarding t-tau and atrophy. The assessment of the A/T/N classification scheme in addition with brain atrophy patterns in MCI, increases the knowledge of the clinical trajectories and the variability within the neurodegeneration domain. This emphasises that individuals with MCI display heterogeneous longitudinal patterns closely connected to their biomarker profiles, which could have important clinical implications.
The Relationship between Cerebral White Matter Integrity and Cognitive Function in Mild Stroke with Basal Ganglia Region Infarcts
Authors: Zuo Li-Jun , Li Zi-Xiao , Zhu Rong-Yan , Chen Yao-Jing , Dong YanHong , Wang Yi-Long , Zhao Xing-Quan , Zhang Zhan-Jun , Sachdev Perminder , Zhang Wei , Wang Yong-Jun 
Published: May 2018

AbstractMild stroke is a known risk factor for dementia. The relationship between cerebral white matter (WM) integrity and cognitive impairment (CI) in mild stroke patients with basal ganglia region infarcts is unknown. Total of 33 stroke patients and 19 age-matched controls underwent diffusion tensor imaging scans and a formal neuropsychological test battery. CI was defined as having a performance score 1.5 SD below the established norm. We compared the differences in Z-scores and Fraction Anisotropy (FA) values among controls, stroke with no CI (NCI) and stroke with CI groups. Multiple linear regressions were performed between FA values in affected regions and neuropsychological tests in stroke patients. The majority of stroke patients were in their 50s (56.90 ± 9.23 years). CI patients exhibited a significantly decreased Z score in visual delayed memory and remarkably decreased FA values in the right external capsule and right fornix (FWE-corrected) compared with NCI patients and controls. In stroke patients, the FA value in the right fornix was positively correlated with delayed visual memory. Mild stroke with basal ganglia region infarcts may be related to widespread abnormality of WM integrity. The lower WM integrity in the right fornix may be a marker of impaired delayed visual memory.
Defined Geldrop Cultures Maintain Neural Precursor Cells
Authors: Vogler Steffen , Prokoph Silvana , Freudenberg Uwe , Binner Marcus , Tsurkan Mikhail , Werner Carsten , Kempermann Gerd 
Published: May 2018

AbstractDistinct micro-environmental properties have been reported to be essential for maintenance of neural precursor cells (NPCs) within the adult brain. Due to high complexity and technical limitations, the natural niche can barely be studied systematically in vivo. By reconstituting selected environmental properties (adhesiveness, proteolytic degradability, and elasticity) in geldrop cultures, we show that NPCs can be maintained stably at high density over an extended period of time (up to 8 days). In both conventional systems, neurospheres and monolayer cultures, they would expand and (in the case of neurospheres) differentiate rapidly. Further, we report a critical dualism between matrix adhesiveness and degradability. Only if both features are functional NPCs stay proliferative. Lastly, Rho-associated protein kinase was identified as part of a pivotal intracellular signaling cascade controlling cell morphology in response to environmental cues inside geldrop cultures. Our findings demonstrate that simple manipulations of the microenvironment in vitro result in an important preservation of stemness features in the cultured precursor cells.
Low-dose anticoagulation after isolated mechanical aortic valve replacement with Liva Nova Bicarbon prosthesis: A post hoc analysis of LOWERING-IT Trial
Authors: Torella Michele , Aquila Iolanda , Chiodini Paolo , Amarelli Cristiano , Romano Gianpaolo , Della Ratta Ester Elena , De Feo Marisa , Della Corte Alessandro , Indolfi Ciro , Torella Daniele , De Santo Luca Salvatore 
Published: May 2018

AbstractThromboembolic complications after cardiac valve replacement are due to a complex interplay between patients’ characteristics, device features and anticoagulation intensity. Subtle design and material differences in available prostheses may thrombosis. We conducted a post-hoc sub-analysis of the LOWERING-IT database to test the safety and feasibility of a low-level oral anticoagulant regime in low-risk patients with aortic LivaNova prosthetic valve replacement. The study population included 148 patients randomized to a low INR target (1.5–2.5; LOW-INR group), and 144 patients to the standard INR (2.0–3.0; CONVENTIONAL-INR group). The non-inferiority of thromboembolic events between LOW-INR and CONVENTIONAL-INR groups was tested. Cumulative follow-up reached 1,545 patient/years. The mean INR was 1.91 ± 0.23 in the LOW-INR group, and 2.59 ± 0.26 in the CONVENTIONAL-INR group (P < 0.001). There were 3 thromboembolic events, all in the CONVENTIONAL-INR group. Comparison of thromboembolic events was not significant. The 1-sided 97.5% exact CI for the difference in primary event proportion was 0.54%, satisfying criteria non-inferiority. Bleeding events were significantly different: 6.61 per 1,000 patient-year in LOW-INR group vs 18.65 per 1,000 patient-year in CONVENTIONAL-INR group (p < 0.045, RR 0.37). In conclusions these data suggest that low-dose anticoagulation is safe in selected patients after aortic LivaNova Bicarbon prosthesis implantation.
Klotho is upregulated in human cardiomyopathy independently of circulating Klotho levels
Authors: Poelzl G. , Ghadge S. K. , Messner M. , Haubner B. , Wuertinger Ph. , Griesmacher A. , Doerler J. , Ensinger C. , Ulmer H. , Zaruba M. M. 
Published: May 2018

AbstractKlotho is an antiaging protein which exerts known cardioprotection. In kidney, trans-membrane Klotho acts as essential co-receptor of fibroblast growth factor 23 (FGF23). In the heart, soluble Klotho (sKlotho) protects from systolic dysfunction independently of FGF23. Here, we analyzed the association of FGF23 and sKlotho upon progression of chronic heart failure (CHF) and analyzed Klotho expression in human hearts. Serum levels of sKlotho and FGF23 were measured in 287 patients with cardiomyopathy (CMP). Tissue samples from CMP (n = 10) and healthy control hearts (n = 10) were analyzed for Klotho mRNA and protein expression. Individuals in the first FGF23 tertile were 4.1 times more likely of freedom from death, heart transplantation or assist device implantation compared to third tertile. No relationship was found between sKlotho and the combined endpoint. Instead, Klotho mRNA encoding the full-length form was upregulated in human CMP hearts. Immunoblotting confirmed upregulation of sKlotho associated with increased expression of proteases involved in cleavage of Klotho suggesting rather local effects of Klotho in the heart. Therefore, we conclude that in contrast to FGF23, serum sKlotho is not associated with disease severity or progression in CHF. Instead, Klotho is expressed and upregulated in diseased hearts, suggesting local paracrine effects.
Competition Elicits more Physical Affiliation between Male than Female Friends
Authors: Benenson Joyce F. , White Maxwell M. , Pandiani Delfina Martinez , Hillyer Lindsay J. , Kantor Sera , Markovits Henry , Wrangham Richard W. 
Published: May 2018

AbstractAcross species, cooperative alliances must withstand internal tensions. The mechanisms by which allies respond to competing against one another have been studied extensively in non-human animals, but much less so in humans. In non-human species, affiliative physical contact and close proximity immediately following a contest are utilized to define reconciliation between opponents. The proportion of conflicts that are reconciled however differs markedly by species and sex. The purpose of this study was to examine whether, like many other social species, humans utilize physical contact and close proximity following a competition between friends, and if so, whether one sex is more likely to exhibit these behaviors. Using a standardized procedure, two same-gender friends competed against one another producing a clear winner and loser. Prior to and following the competition, the friends relaxed together. Videotapes of the relaxation periods showed that male friends spent more time than female friends engaged in affiliative physical contact and close proximity both before and after the competition, but not during a brief intervening cooperative task. These results suggest that in the face of competing self-interests, physical contact and close proximity facilitate repair of males’ more than females’ valuable relationships.
Structure and Chemical Organization in Damselfly Calopteryx haemorrhoidalis Wings: A Spatially Resolved FTIR and XRF Analysis with Synchrotron Radiation
Authors: Stuhr Susan , Truong Vi Khanh , Vongsvivut Jitraporn , Senkbeil Tobias , Yang Yang , Al Kobaisi Mohammad , Baulin Vladimir A. , Werner Marco , Rubanov Sergey , Tobin Mark J. , Cloetens Peter , Rosenhahn Axel , Lamb Robert N. , Luque Pere , Marchant Richard , Ivanova Elena P. 
Published: May 2018

AbstractInsects represent the majority of known animal species and exploit a variety of fascinating nanotechnological concepts. We investigated the wings of the damselfly Calopteryx haemorrhoidalis, whose males have dark pigmented wings and females have slightly pigmented wings. We used scanning electron microscopy (SEM) and nanoscale synchrotron X-ray fluorescence (XRF) microscopy analysis for characterizing the nanostructure and the elemental distribution of the wings, respectively. The spatially resolved distribution of the organic constituents was examined by synchrotron Fourier transform infrared (s-FTIR) microspectroscopy and subsequently analyzed using hierarchical cluster analysis. The chemical distribution across the wing was rather uniform with no evidence of melanin in female wings, but with a high content of melanin in male wings. Our data revealed a fiber-like structure of the hairs and confirmed the presence of voids close to its base connecting the hairs to the damselfly wings. Within these voids, all detected elements were found to be locally depleted. Structure and elemental contents varied between wing membranes, hairs and veins. The elemental distribution across the membrane was rather uniform, with higher Ca, Cu and Zn levels in the male damselfly wing membranes.
The C/EBPβ LIP isoform rescues loss of C/EBPβ function in the mouse
Authors: Bégay Valérie , Baumeier Christian , Zimmermann Karin , Heuser Arnd , Leutz Achim 
Published: May 2018

AbstractThe transcription factor C/EBPβ regulates hematopoiesis, bone, liver, fat, and skin homeostasis, and female reproduction. C/EBPβ protein expression from its single transcript occurs by alternative in-frame translation initiation at consecutive start sites to generate three isoforms, two long (LAP*, LAP) and one truncated (LIP), with the same C-terminal bZip dimerization domain. The long C/EBPβ isoforms are considered gene activators, whereas the LIP isoform reportedly acts as a dominant-negative repressor. Here, we tested the putative repressor functions of the C/EBPβ LIP isoform in mice by comparing monoallelic WT or LIP knockin mice with Cebpb knockout mice, in combination with monoallelic Cebpa mice. The C/EBPβ LIP isoform was sufficient to function in coordination with C/EBPα in murine development, adipose tissue and sebocyte differentiation, and female fertility. Thus, the C/EBPβ LIP isoform likely has more physiological functions than its currently known role as a dominant-negative inhibitor, which are more complex than anticipated.
Measurement of temperature and density using non-collective X-ray Thomson scattering in pulsed power produced warm dense plasmas
Authors: Valenzuela J. C. , Krauland C. , Mariscal D. , Krasheninnikov I. , Niemann C. , Ma T. , Mabey P. , Gregori G. , Wiewior P. , Covington A. M. , Beg F. N. 
Published: May 2018

AbstractWe present the first experimental measurement of temperature and density of a warm dense plasma produced by a pulsed power driver at the Nevada Terawatt Facility (NTF). In the early phases of discharge, most of the mass remains in the core, and it has been challenging to diagnose with traditional methods, e.g. optical probing, because of the high density and low temperature. Accurate knowledge of the transport coefficients as well as the thermodynamic state of the plasma is important to precisely test or develop theoretical models. Here, we have used spectrally resolved non-collective X-ray Thomson scattering to characterize the dense core region. We used a graphite load driven by the Zebra current generator (0.6 MA in 200 ns rise time) and the Ti He-α line produced by irradiating a Ti target with the Leopard laser (30 J, 0.8 ns) as an X-ray probing source. Using this configuration, we obtained a signal-to-noise ratio ~2.5 for the scattered signal. By fitting the experimental data with predicted spectra, we measured T = 2±1.9 eV, ρ = 0.6±0.5 gr/cc, 70 ns into the current pulse. The complexity of the dense core is revealed by the electrons in the dense core that are found to be degenerate and weakly coupled, while the ions remain highly coupled.
Coupling a Single Nitrogen-Vacancy Center in Nanodiamond to Superparamagnetic Nanoparticles
Authors: Sadzak Nikola , Héritier Martin , Benson Oliver 
Published: May 2018

AbstractSingle nitrogen-vacancy (NV) defect centers in diamond have been exploited as single photon sources and spin qubits due to their room-temperature robust quantum light emission and long electron spin coherence times. They were coupled to a manifold of structures, such as optical cavities, plasmonic waveguides, and even injected into living cells to study fundamental interactions of various nature at the nanoscale. Of particular interest are applications of NVs as quantum sensors for local nanomagnetometry. Here, we employ a nanomanipulation approach to couple a single NV center in a nanodiamond to a single few-nm superparamagnetic iron oxide nanoparticle in a controlled way. After measuring via relaxometry the magnetic particle spin-noise, we take advantage of the crystal strain m
s
= ± 1 spin level separation to detect the superparamagnetic particle’s effect in presence of a driving AC magnetic field. Our experiments provide detailed insight in the behavior of such particles with respect to high frequency fields. The approach can be extended to the investigation of increasingly complex, but controlled nanomagnetic hybrid particle assemblies. Moreover, our results suggest that superparamagnetic nanoparticles can amplify local magnetic interactions in order to improve the sensitivity of diamond nanosensors for specific measurement scenarios.
Exploring the diversity-stability paradigm using sponge microbial communities
Authors: Glasl Bettina , Smith Caitlin E. , Bourne David G. , Webster Nicole S. 
Published: May 2018

AbstractA key concept in theoretical ecology is the positive correlation between biodiversity and ecosystem stability. When applying this diversity-stability concept to host-associated microbiomes, the following questions emerge: (1) Does microbial diversity influence the stability of microbiomes upon environmental fluctuations? (2) Do hosts that harbor highversuslow microbial diversity differ in their stress response? To test the diversity-stability concept in host-associated microbiomes, we exposed six marine sponge species with varying levels of microbial diversity to non-lethal salinity disturbances and followed their microbial composition over time using 16S rRNA gene amplicon sequencing. No signs of sponge stress were evident following salinity amendment and microbiomes exhibited compositional resistance irrespective of their microbial diversity. Compositional stability of the sponge microbiome manifests itself at distinct host taxonomic and host microbial diversity groups, with (1) stable host genotype-specific microbiomes at oligotype-level; (2) stable host species-specific microbiomes at genus-level; and (3) stable and specific microbiomes at phylum-level for hosts with highversuslow microbial diversity. The resistance of sponge microbiomes together with the overall stability of sponge holobionts upon salinity fluctuations suggest that the stability-diversity concept does not appear to hold for sponge microbiomes and provides further evidence for the widely recognized environmental tolerance of sponges.
Crystallisation in basaltic magmas revealed via in situ 4D synchrotron X-ray microtomography
Authors: Polacci M. , Arzilli F. , La Spina G. , Le Gall N. , Cai B. , Hartley M. E. , Di Genova D. , Vo N. T. , Nonni S. , Atwood R. C. , Llewellin E. W. , Lee P. D. , Burton M. R. 
Published: May 2018

AbstractMagma crystallisation is a fundamental process driving eruptions and controlling the style of volcanic activity. Crystal nucleation delay, heterogeneous and homogeneous nucleation and crystal growth are all time-dependent processes, however, there is a paucity of real-time experimental data on crystal nucleation and growth kinetics, particularly at the beginning of crystallisation when conditions are far from equilibrium. Here, we reveal the first in situ 3D time-dependent observations of crystal nucleation and growth kinetics in a natural magma, reproducing the crystallisation occurring in real-time during a lava flow, by combining a bespoke high-temperature environmental cell with fast synchrotron X-ray microtomography. We find that both crystal nucleation and growth occur in pulses, with the first crystallisation wave producing a relatively low volume fraction of crystals and hence negligible influence on magma viscosity. This result explains why some lava flows cover kilometres in a few hours from eruption inception, highlighting the hazard posed by fast-moving lava flows. We use our observations to quantify disequilibrium crystallisation in basaltic magmas using an empirical model. Our results demonstrate the potential of in situ 3D time-dependent experiments and have fundamental implications for the rheological evolution of basaltic lava flows, aiding flow modelling, eruption forecasting and hazard management.
Male age is associated with extra-pair paternity, but not with extra-pair mating behaviour
Authors: Girndt Antje , Chng Charlotte Wen Ting , Burke Terry , Schroeder Julia 
Published: May 2018

AbstractExtra-pair paternity is the result of copulation between a female and a male other than her social partner. In socially monogamous birds, old males are most likely to sire extra-pair offspring. The male manipulation and female choice hypotheses predict that age-specific male mating behaviour could explain this old-over-young male advantage. These hypotheses have been difficult to test because copulations and the individuals involved are hard to observe. Here, we studied the mating behaviour and pairing contexts of captive house sparrows, Passer domesticus. Our set-up mimicked the complex social environment experienced by wild house sparrows. We found that middle-aged males, which would be considered old in natural populations, gained most extra-pair paternity. However, both, female solicitation behaviour and subsequent extra-pair matings were not associated with male age. Further, copulations were more likely when solicited by females than when initiated by males (i.e. unsolicited copulations). Male initiated within-pair copulations were more common than male initiated extra-pair copulations. To conclude, our results did not support either hypothesis regarding age-specific male mating behaviour. Instead, female choice, independent of male age, governed copulation success, especially in an extra-pair context. Post-copulatory mechanisms might determine why older males sire more extra-pair offspring.
Environmental responsiveness of tubulin glutamylation in sensory cilia is regulated by the p38 MAPK pathway
Authors: Kimura Yoshishige , Tsutsumi Koji , Konno Alu , Ikegami Koji , Hameed Saira , Kaneko Tomomi , Kaplan Oktay Ismail , Teramoto Takayuki , Fujiwara Manabi , Ishihara Takeshi , Blacque Oliver E. , Setou Mitsutoshi 
Published: May 2018

AbstractGlutamylation is a post-translational modification found on tubulin that can alter the interaction between microtubules (MTs) and associated proteins. The molecular mechanisms regulating tubulin glutamylation in response to the environment are not well understood. Here, we show that in the sensory cilia of Caenorhabditis elegans, tubulin glutamylation is upregulated in response to various signals such as temperature, osmolality, and dietary conditions. Similarly, tubulin glutamylation is modified in mammalian photoreceptor cells following light adaptation. A tubulin glutamate ligase gene ttll-4, which is essential for tubulin glutamylation of axonemal MTs in sensory cilia, is activated by p38 MAPK. Amino acid substitution of TTLL-4 has revealed that a Thr residue (a putative MAPK-phosphorylation site) is required for enhancement of tubulin glutamylation. Intraflagellar transport (IFT), a bidirectional trafficking system specifically observed along axonemal MTs, is required for the formation, maintenance, and function of sensory cilia. Measurement of the velocity of IFT particles revealed that starvation accelerates IFT, which was also dependent on the Thr residue of TTLL-4. Similarly, starvation-induced attenuation of avoidance behaviour from high osmolality conditions was also dependent on ttll-4. Our data suggest that a novel evolutionarily conserved regulatory system exists for tubulin glutamylation in sensory cilia in response to the environment.