bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular cystatin SN and cathepsin B prevent cellular senescence by inhibiting abnormal glycogen accumulation
Authors: Oh Sang-Seok , Park Soojong , Lee Ki-Won , Madhi Hamadi , Park Sae Gwang , Lee Hee Gu , Cho Yong-Yeon , Yoo Jiyun , Dong Kim Kwang 
Published: April 2017

AbstractCystatin SN (CST1), a known inhibitor of cathepsin B (CatB), has important roles in tumor development. Paradoxically, CatB is a member of the cysteine cathepsin family that acts in cellular processes, such as tumor development and invasion. However, the relationship between CST1 and CatB, and their roles in tumor development are poorly understood. In this study, we observed that the knockdown of CST1 induced the activity of senescence-associated β-galactosidase, a marker of cellular senescence, and expression of senescence-associated secretory phenotype genes, including interleukin-6 and chemokine (C-C motif) ligand 20, in MDA-MB-231 and SW480 cancer cells. Furthermore, CST1 knockdown decreased extracellular CatB activity, and direct CatB inhibition, using specific inhibitors or shCatB, induced cellular senescence. Reconstitution of CST1 restored CatB activity and inhibited cellular senescence in CST1 knockdown cells. CST1 knockdown or CatB inhibition increased glycogen synthase (GS) kinase 3β phosphorylation at serine 9, resulting in the activation of GS and the induction of glycogen accumulation associated with cellular senescence. Importantly, CST1 knockdown suppressed cancer cell proliferation, soft agar colony growth and tumor growth in a xenograft model. These results indicate that CST1-mediated extracellular CatB activity enhances tumor development by preventing cellular senescence. Our findings suggest that antagonists of CST1 or inhibitors of CatB are potential anticancer agents.
Highly selective inhibition of histone demethylases by de novo macrocyclic peptides
Authors: Kawamura Akane , Münzel Martin , Kojima Tatsuya , Yapp Clarence , Bhushan Bhaskar , Goto Yuki , Tumber Anthony , Katoh Takayuki , King Oliver N. F. , Passioura Toby , Walport Louise J. , Hatch Stephanie B. , Madden Sarah , Müller Susanne , Brennan Paul E. , Chowdhury Rasheduzzaman , Hopkinson Richard J. , Suga Hiroaki , Schofield Christopher J. 
Published: April 2017

AbstractThe JmjC histone demethylases (KDMs) are linked to tumour cell proliferation and are current cancer targets; however, very few highly selective inhibitors for these are available. Here we report cyclic peptide inhibitors of the KDM4A-C with selectivity over other KDMs/2OG oxygenases, including closely related KDM4D/E isoforms. Crystal structures and biochemical analyses of one of the inhibitors (CP2) with KDM4A reveals that CP2 binds differently to, but competes with, histone substrates in the active site. Substitution of the active site binding arginine of CP2 to N-ɛ-trimethyl-lysine or methylated arginine results in cyclic peptide substrates, indicating that KDM4s may act on non-histone substrates. Targeted modifications to CP2 based on crystallographic and mass spectrometry analyses results in variants with greater proteolytic robustness. Peptide dosing in cells manifests KDM4A target stabilization. Although further development is required to optimize cellular activity, the results reveal the feasibility of highly selective non-metal chelating, substrate-competitive inhibitors of the JmjC KDMs.
Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation
Authors: Ognjanovski Nicolette , Schaeffer Samantha , Wu Jiaxing , Mofakham Sima , Maruyama Daniel , Zochowski Michal , Aton Sara J. 
Published: April 2017

AbstractActivity in hippocampal area CA1 is essential for consolidating episodic memories, but it is unclear how CA1 activity patterns drive memory formation. We find that in the hours following single-trial contextual fear conditioning (CFC), fast-spiking interneurons (which typically express parvalbumin (PV)) show greater firing coherence with CA1 network oscillations. Post-CFC inhibition of PV+ interneurons blocks fear memory consolidation. This effect is associated with loss of two network changes associated with normal consolidation: (1) augmented sleep-associated delta (0.5–4 Hz), theta (4–12 Hz) and ripple (150–250 Hz) oscillations; and (2) stabilization of CA1 neurons’ functional connectivity patterns. Rhythmic activation of PV+ interneurons increases CA1 network coherence and leads to a sustained increase in the strength and stability of functional connections between neurons. Our results suggest that immediately following learning, PV+ interneurons drive CA1 oscillations and reactivation of CA1 ensembles, which directly promotes network plasticity and long-term memory formation.
Impacts of alpine wetland degradation on the composition, diversity and trophic structure of soil nematodes on the Qinghai-Tibetan Plateau
Authors: Wu Pengfei , Zhang Hongzhi , Cui Liwei , Wickings Kyle , Fu Shenglei , Wang Changting 
Published: April 2017

AbstractAlpine wetlands on the Qinghai-Tibetan Plateau are undergoing degradation. However, little is known regarding the response of soil nematodes to this degradation. We conducted investigations in a wet meadow (WM), a grassland meadow (GM), a moderately degraded meadow (MDM) and a severely degraded meadow (SDM) from April to October 2011. The nematode community taxonomic composition was similar in the WM, GM and MDM and differed from that in the SDM. The abundance declined significantly from the WM to the SDM. The taxonomic richness and Shannon index were comparable between the WM and MDM but were significantly lower in the SDM, and the Pielou evenness showed the opposite pattern. The composition, abundance and diversity in the WM and SDM were relatively stable over time compared with other habitats. The abundances of all trophic groups, aside from predators, decreased with degradation. The relative abundances of herbivores, bacterivores, predators and fungivores were stable, while those of omnivores and algivores responded negatively to degradation. Changes in the nematode community were mainly driven by plant species richness and soil available N. Our results demonstrate that alpine wetland degradation significantly affects the soil nematode communities, suppressing but not shifting the main energy pathways through the soil nematode communities.
Plasticity within excitatory and inhibitory pathways of the vestibulo-spinal circuitry guides changes in motor performance
Authors: Mitchell Diana E. , Della Santina Charles C. , Cullen Kathleen E. 
Published: April 2017

AbstractInvestigations of behaviors with well-characterized circuitry are required to understand how the brain learns new motor skills and ensures existing behaviors remain appropriately calibrated over time. Accordingly, here we recorded from neurons within different sites of the vestibulo-spinal circuitry of behaving macaque monkeys during temporally precise activation of vestibular afferents. Behaviorally relevant patterns of vestibular nerve activation generated a rapid and substantial decrease in the monosynaptic responses recorded at the first central stage of processing from neurons receiving direct input from vestibular afferents within minutes, as well as a decrease in the compensatory reflex response that lasted up to 8 hours. In contrast, afferent responses to this same stimulation remained constant, indicating that plasticity was not induced at the level of the periphery but rather at the afferent-central neuron synapse. Strikingly, the responses of neurons within indirect brainstem pathways also remained constant, even though the efficacy of their central input was significantly reduced. Taken together, our results show that rapid plasticity at the first central stage of vestibulo-spinal pathways can guide changes in motor performance, and that complementary plasticity on the same millisecond time scale within inhibitory vestibular nuclei networks contributes to ensuring a relatively robust behavioral output.
Rapid and accurate peripheral nerve imaging by multipoint Raman spectroscopy
Authors: Kumamoto Yasuaki , Harada Yoshinori , Tanaka Hideo , Takamatsu Tetsuro 
Published: April 2017

AbstractRaman spectroscopy allows label-free, minimally invasive, and accurate detection of peripheral nerves. However, the conventional Raman imaging technique is time-consuming when measuring a large area of a sample. Establishing a method for rapidly acquiring spatial distribution of a bundle of peripheral nerve fibers is an essential step for Raman spectroscopy towards application in clinical surgery. Here we present a multipoint Raman spectroscopic technique for rapid peripheral nerve imaging. In only 5 seconds, spectra at 32 points situated on ex vivo rat peripheral nerve bundles and adjoining connective tissues were acquired. Principal component regression and discriminant analysis of spectra revealed that the sensitivity, specificity and accuracy for nerve detection were 85.8%, 96.0%, and 90.8%, respectively. Of 158 peripheral nerves, 152 (96.2%) showed ratio of the number of nerve-positive prediction points to the total measurement points being 0.4 or larger, whereas 119 (99.2%) connective tissues among 120 showed ratio smaller than 0.4. Based on the ratio and a bright-field image of the sample, accurate visualization of peripheral nerves was implemented. The results indicated that the multipoint Raman spectroscopic technique is capable of rapid and accurate peripheral nerve imaging.
Himalayan black bulbuls (Hypsipetes leucocephalus niggerimus) exhibit sexual dichromatism under ultraviolet light that is invisible to the human eye
Authors: Hung Hsin-Yi , Yeung Carol K. L. , Omland Kevin E. , Yao Cheng-Te , Yao Chiou-Ju , Li Shou-Hsien 
Published: April 2017

AbstractSexual dichromatism is a key proxy for the intensity of sexual selection. Studies of dichromatism in birds may, however, have underestimated the intensity and complexity of sexual selection because they used museum specimens alone without taking colour-fading into account or only measured conspicuous visual traits in live animals. We investigated whether the Himalayan black bulbul (Hypsipetes leucocephalus nigerrimus), which is sexually monomorphic to the human eye, exhibits sexual dichromatism distinguishable by a spectrometer. We measured the reflectance (within both the human visual perceptive and the ultraviolet ranges) of two carotenoid-based parts and eight dull and melanin-based parts for each individual live bird or museum skin sampled. According to an avian model of colour discrimination thresholds, we found that males exhibited perceptibly redder beaks, brighter tarsi and darker plumage than did females. This suggests the existence of multiple cryptic sexually dichromatic traits within this species. Moreover, we also observed detectable colour fading in the museum skin specimens compared with the live birds, indicating that sexual dichromatism could be underestimated if analysed using skin specimens alone.
Connecting myelin-related and synaptic dysfunction in schizophrenia with SNP-rich gene expression hubs
Authors: Hegyi Hedi 
Published: April 2017

AbstractCombining genome-wide mapping of SNP-rich regions in schizophrenics and gene expression data in all brain compartments across the human life span revealed that genes with promoters most frequently mutated in schizophrenia are expression hubs interacting with far more genes than the rest of the genome. We summed up the differentially methylated “expression neighbors” of genes that fall into one of 108 distinct schizophrenia-associated loci with high number of SNPs. Surprisingly, the number of expression neighbors of the genes in these loci were 35 times higher for the positively correlating genes (32 times higher for the negatively correlating ones) than for the rest of the ~16000 genes. While the genes in the 108 loci have little known impact in schizophrenia, we identified many more known schizophrenia-related important genes with a high degree of connectedness (e.g. MOBP, SYNGR1 and DGCR6), validating our approach. Both the most connected positive and negative hubs affected synapse-related genes the most, supporting the synaptic origin of schizophrenia. At least half of the top genes in both the correlating and anti-correlating categories are cancer-related, including oncogenes (RRAS and ALDOA), providing further insight into the observed inverse relationship between the two diseases.
Clay illuviation provides a long-term sink for C sequestration in subsoils
Authors: Torres-Sallan Gemma , Schulte Rogier P. O. , Lanigan Gary J. , Byrne Kenneth A. , Reidy Brian , Simó Iolanda , Six Johan , Creamer Rachel E. 
Published: April 2017

AbstractSoil plays a key role in the global carbon (C) cycle. Most current assessments of SOC stocks and the guidelines given by Intergovernmental Panel on Climate Change (IPCC) focus on the top 30 cm of soil. Our research shows that, when considering only total quantities, most of the SOC stocks are found in this top layer. However, not all forms of SOC are equally valuable as long-term stable stores of carbon: the majority of SOC is available for mineralisation and can potentially be re-emitted to the atmosphere. SOC associated with micro-aggregates and silt plus clay fractions is more stable and therefore represents a long-term carbon store. Our research shows that most of this stable carbon is located at depths below 30 cm (42% of subsoil SOC is located in microaggregates and silt and clay, compared to 16% in the topsoil), specifically in soils that are subject to clay illuviation. This has implications for land management decisions in temperate grassland regions, defining the trade-offs between primary productivity and C emissions in clay-illuviated soils, as a result of drainage. Therefore, climate smart land management should consider the balance between SOC stabilisation in topsoils for productivity versus sequestration in subsoils for climate mitigation.
Cassava foliage affects the microbial diversity of Chinese indigenous geese caecum using 16S rRNA sequencing
Authors: Li Mao , Zhou Hanlin , Pan Xiangyu , Xu Tieshan , Zhang Zhenwen , Zi Xuejuan , Jiang Yu 
Published: April 2017

AbstractGeese are extremely adept in utilizing plant-derived roughage within their diet. However, the intestinal microbiome of geese remains limited, especially the dietary effect on microbial diversity. Cassava foliage was widely used in animal feed, but little information is available for geese. In this study, the geese were fed with control diet (CK), experimental diet supplemented with 5% cassava foliage (CF5) or 10% (CF10) for 42 days, respectively. The cecal samples were collected after animals were killed. High-throughput sequencing technology was used to investigate the microbial diversity in the caecum of geese with different dietary supplements. Taxonomic analysis indicated that the predominant phyla were distinct with different dietary treatments. The phyla Firmicutes (51.4%), Bacteroidetes (29.55%) and Proteobacteria (7.90%) were dominant in the CK group, but Bacteroidetes (65.19% and 67.29%,) Firmicutes (18.01% and 17.39%), Proteobacteria (8.72% and 10.18%), Synergistete (2.51% and 1.76%) and Spirochaetes (2.60% and 1.46%) were dominant in CF5 and CF10 groups. The abundance of Firmicutes was negatively correlated with the supplementation of cassava foliage. However, the abundance of Bacteroidetes and Proteobacteria were positively correlated with the supplementation of cassava foliage. Our study also revealed that the microbial communities were significantly different at genus levels. Genes related to nutrient and energy metabolism, immunity and signal transduction pathways were primarily enriched by the microbiome.
Mushroom biomass and diversity are driven by different spatio-temporal scales along Mediterranean elevation gradients
Authors: Alday Josu G. , Martínez de Aragón Juan , de-Miguel Sergio , Bonet José Antonio 
Published: April 2017

AbstractMushrooms are important non-wood-forest-products in many Mediterranean ecosystems, being highly vulnerable to climate change. However, the ecological scales of variation of mushroom productivity and diversity, and climate dependence has been usually overlooked due to a lack of available data. We determined the spatio-temporal variability of epigeous sporocarps and the climatic factors driving their fruiting to plan future sustainable management of wild mushrooms production. We collected fruiting bodies in Pinus sylvestris stands along an elevation gradient for 8 consecutive years. Overall, sporocarp biomass was mainly dependent on inter-annual variations, whereas richness was more spatial-scale dependent. Elevation was not significant, but there were clear elevational differences in biomass and richness patterns between ectomycorrhizal and saprotrophic guilds. The main driver of variation was late-summer-early-autumn precipitation. Thus, different scale processes (inter-annual vs. spatial-scale) drive sporocarp biomass and diversity patterns; temporal effects for biomass and ectomycorrhizal fungi vs. spatial scale for diversity and saprotrophic fungi. The significant role of precipitation across fungal guilds and spatio-temporal scales indicates that it is a limiting resource controlling sporocarp production and diversity in Mediterranean regions. The high spatial and temporal variability of mushrooms emphasize the need for long-term datasets of multiple spatial points to effectively characterize fungal fruiting patterns.
High-precision 14C and 40Ar/39Ar dating of the Campanian Ignimbrite (Y-5) reconciles the time-scales of climatic-cultural processes at 40 ka
Authors: Giaccio Biagio , Hajdas Irka , Isaia Roberto , Deino Alan , Nomade Sebastien 
Published: April 2017

AbstractThe Late Pleistocene Campanian Ignimbrite (CI) super-eruption (Southern Italy) is the largest known volcanic event in the Mediterranean area. The CI tephra is widely dispersed through western Eurasia and occurs in close stratigraphic association with significant palaeoclimatic and Palaeolithic cultural events. Here we present new high-precision 14C (34.29 ± 0.09 14C kyr BP, 1σ) and 40Ar/39Ar (39.85 ± 0.14 ka, 95% confidence level) dating results for the age of the CI eruption, which substantially improve upon or augment previous age determinations and permit fuller exploitation of the chronological potential of the CI tephra marker. These results provide a robust pair of 14C and 40Ar/39Ar ages for refining both the radiocarbon calibration curve and the Late Pleistocene time-scale at ca. 40 ka. In addition, these new age constraints provide compelling chronological evidence for the significance of the combined influence of the CI eruption and Heinrich Event 4 on European climate and potentially evolutionary processes of the Early Upper Palaeolithic.
Anti-tumour activity of tivozanib, a pan-inhibitor of VEGF receptors, in therapy-resistant ovarian carcinoma cells
Authors: Momeny Majid , Sabourinejad Zahra , Zarrinrad Ghazaleh , Moghaddaskho Farima , Eyvani Haniyeh , Yousefi Hassan , Mirshahvaladi Shahab , Poursani Ensieh M. , Barghi Farinaz , Poursheikhani Arash , Dardaei Leila , Bashash Davood , Ghazi-Khansari Mahmoud , Tavangar Seyyed M. , Dehpour Ahmad R. , Yaghmaie Marjan , Alimoghaddam Kamran , Ghavamzadeh Ardeshir , Ghaffari Seyed H. 
Published: April 2017

AbstractEpithelial ovarian cancer (EOC) is the most fatal gynaecological malignancy. Despite initial therapeutic response, the majority of advanced-stage patients relapse and succumb to chemoresistant disease. Overcoming drug resistance is the key to successful treatment of EOC. Members of vascular endothelial growth factor (VEGF) family are overexpressed in EOC and play key roles in its malignant progression though their contribution in development of the chemoresistant disease remains elusive. Here we show that expression of the VEGF family is higher in therapy-resistant EOC cells compared to sensitive ones. Overexpression of VEGFR2 correlated with resistance to cisplatin and combination with VEGFR2-inhibitor apatinib synergistically increased cisplatin sensitivity. Tivozanib, a pan-inhibitor of VEGF receptors, reduced proliferation of the chemoresistant EOC cells through induction of G2/M cell cycle arrest and apoptotic cell death. Tivozanib decreased invasive potential of these cells, concomitant with reduction of intercellular adhesion molecule-1 (ICAM-1) and diminishing the enzymatic activity of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-2 (MMP-2). Moreover, tivozanib synergistically enhanced anti-tumour effects of EGFR-directed therapies including erlotinib. These findings suggest that the VEGF pathway has potential as a therapeutic target in therapy-resistant EOC and VEGFR blockade by tivozanib may yield stronger anti-tumour efficacy and circumvent resistance to EGFR-directed therapies.
Neuroanatomical correlates of forgiving unintentional harms
Authors: Patil Indrajeet , Calò Marta , Fornasier Federico , Young Liane , Silani Giorgia 
Published: April 2017

AbstractMature moral judgments rely on the consideration of a perpetrator’s mental state as well as harmfulness of the outcomes produced. Prior work has focused primarily on the functional correlates of how intent information is neurally represented for moral judgments, but few studies have investigated whether individual differences in neuroanatomy can also explain variation in moral judgments. In the current study, we conducted voxel-based morphometry analyses to address this question. We found that local grey matter volume in the left anterior superior temporal sulcus, a region in the functionally defined theory of mind or mentalizing network, was associated with the degree to which participants relied on information about innocent intentions to forgive accidental harms. Our findings provide further support for the key role of mentalizing in the forgiveness of accidental harms and contribute preliminary evidence for the neuroanatomical basis of individual differences in moral judgments.
Visual acuity of the honey bee retina and the limits for feature detection
Authors: Rigosi Elisa , Wiederman Steven D. , O’Carroll David C. 
Published: April 2017

AbstractVisual abilities of the honey bee have been studied for more than 100 years, recently revealing unexpectedly sophisticated cognitive skills rivalling those of vertebrates. However, the physiological limits of the honey bee eye have been largely unaddressed and only studied in an unnatural, dark state. Using a bright display and intracellular recordings, we here systematically investigated the angular sensitivity across the light adapted eye of honey bee foragers. Angular sensitivity is a measure of photoreceptor receptive field size and thus small values indicate higher visual acuity. Our recordings reveal a fronto-ventral acute zone in which angular sensitivity falls below 1.9°, some 30% smaller than previously reported. By measuring receptor noise and responses to moving dark objects, we also obtained direct measures of the smallest features detectable by the retina. In the frontal eye, single photoreceptors respond to objects as small as 0.6° × 0.6°, with >99% reliability. This indicates that honey bee foragers possess significantly better resolution than previously reported or estimated behaviourally, and commonly assumed in modelling of bee acuity.