bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artemether attenuates LPS-induced inflammatory bone loss by inhibiting osteoclastogenesis and bone resorption via suppression of MAPK signaling pathway
Authors: Wu Haobo , Hu Bin , Zhou Xiaopeng , Zhou Chenhe , Meng Jiahong , Yang Yute , Zhao Xiang , Shi Zhongli , Yan Shigui 
Published: April 2018

AbstractOsteolysis is an osteolytic lesion featured by enhanced osteoclast formation and potent bone erosion. Lacking of effective regimen for treatment of the pathological process highlights the importance of identifying agents that can suppress the differentiation and function of osteoclast. Artemether is a natural compound derived from Artemisia annua L. and it is popularized for the treatment of malaria. In present study, we demonstrated that artemether could suppress RANKL-induced osteoclastogenesis and expression of osteoclast marker genes such as tartrate-resistant acid phosphatase, cathepsin K, matrix metalloproteinase 9, nuclear factor of activated T-cell cytoplasmic 1, and dendritic cell-specific transmembrane protein. It inhibited the osteoclastic bone resorption in a dose-dependent manner in vitro. Furthermore, artemether attenuated RANKL-induced MAPKs (ERK, JNK, p-38) activity. In addition, we have showed that artemether was able to mitigate bone erosion in a murine model of LPS-induced inflammatory bone loss. Taken together, these findings suggest that artemether reduces inflammatory bone loss via inhibition of MAPKs activation during osteoclast differentiation, and it might be a potential candidate for the treatment of osteoclast-related disorders.
CCDC102B confers risk of low vision and blindness in high myopia
Authors: Hosoda Yoshikatsu , Yoshikawa Munemitsu , Miyake Masahiro , Tabara Yasuharu , Shimada Noriaki , Zhao Wanting , Oishi Akio , Nakanishi Hideo , Hata Masayuki , Akagi Tadamichi , Ooto Sotaro , Nagaoka Natsuko , Fang Yuxin ,   Nagahama Study group, Kawaguchi Takahisa , Setoh Kazuya , Takahashi Yoshimitsu , Kosugi Shinji , Nakayama Takeo , Ohno-Matsui Kyoko , Cheng Ching-Yu , Saw Seang Mei , Yamada Ryo , Matsuda Fumihiko , Tsujikawa Akitaka , Yamashiro Kenji 
Published: April 2018

AbstractThe incidence of high myopia is increasing worldwide with myopic maculopathy, a complication of myopia, often progressing to blindness. Our two-stage genome-wide association study of myopic maculopathy identifies a susceptibility locus at rs11873439 in an intron of CCDC102B (P = 1.77 × 10−12 and Pcorr = 1.61 × 10−10). In contrast, this SNP is not significantly associated with myopia itself. The association between rs11873439 and myopic maculopathy is further confirmed in 2317 highly myopic patients (P = 2.40 × 10−6 and Pcorr = 1.72 × 10−4). CCDC102B is strongly expressed in the retinal pigment epithelium and choroids, where atrophic changes initially occur in myopic maculopathy. The development of myopic maculopathy thus likely exhibits a unique background apart from the development of myopia itself; elucidation of the roles of CCDC102B in myopic maculopathy development may thus provide insights into preventive methods for blindness in patients with high myopia.
WASP-mediated regulation of anti-inflammatory macrophages is IL-10 dependent and is critical for intestinal homeostasis
Authors: Biswas Amlan , Shouval Dror S. , Griffith Alexandra , Goettel Jeremy A. , Field Michael , Kang Yu Hui , Konnikova Liza , Janssen Erin , Redhu Naresh Singh , Thrasher Adrian J. , Chatila Talal , Kuchroo Vijay K. , Geha Raif S , Notarangelo Luigi D. , Pai Sung-Yun , Horwitz Bruce H. , Snapper Scott B. 
Published: April 2018

AbstractMutations in Wiskott–Aldrich syndrome protein (WASP) cause autoimmune sequelae including colitis. Yet, how WASP mediates mucosal homeostasis is not fully understood. Here we show that WASP-mediated regulation of anti-inflammatory macrophages is critical for mucosal homeostasis and immune tolerance. The generation and function of anti-inflammatory macrophages are defective in both human and mice in the absence of WASP. Expression of WASP specifically in macrophages, but not in dendritic cells, is critical for regulation of colitis development. Importantly, transfer of WT anti-inflammatory macrophages prevents the development of colitis. DOCK8-deficient macrophages phenocopy the altered macrophage properties associated with WASP deficiency. Mechanistically, we show that both WASP and DOCK8 regulates macrophage function by modulating IL-10-dependent STAT3 phosphorylation. Overall, our study indicates that anti-inflammatory macrophage function and mucosal immune tolerance require both WASP and DOCK8, and that IL-10 signalling modulates a WASP-DOCK8 complex.
The southern ocean meridional overturning in the sea-ice sector is driven by freshwater fluxes
Authors: Pellichero Violaine , Sallée Jean-Baptiste , Chapman Christopher C. , Downes Stephanie M. 
Published: April 2018

AbstractThe oceans are traversed by a large-scale overturning circulation, essential for the climate system as it sets the rate at which the deep ocean interacts with the atmosphere. The main region where deep waters reach the surface is in the Southern Ocean, where they are transformed by interactions with the atmosphere and sea-ice. Here, we present an observation-based estimate of the rate of overturning sustained by surface buoyancy fluxes in the Southern Ocean sea-ice sector. In this region, the seasonal growth and melt of sea-ice dominate water-mass transformations. Both sea-ice freezing and melting act as a pump, removing freshwater from high latitudes and transporting it to lower latitudes, driving a large-scale circulation that upwells 27 ± 7 Sv of deep water to the surface. The upwelled water is then transformed into 22 ± 4 Sv of lighter water and 5 ± 5 Sv into denser layers that feed an upper and lower overturning cell, respectively.
A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression
Authors: Farinello Diego , Wozińska Monika , Lenti Elisa , Genovese Luca , Bianchessi Silvia , Migliori Edoardo , Sacchetti Nicolò , di Lillo Alessia , Bertilaccio Maria Teresa Sabrina , de Lalla Claudia , Valsecchi Roberta , Gleave Sabrina Bascones , Lligé David , Scielzo Cristina , Mauri Laura , Ciampa Maria Grazia , Scarfò Lydia , Bernardi Rosa , Lazarevic Dejan , Gonzalez-Farre Blanca , Bongiovanni Lucia , Campo Elias , Cerutti Andrea , Ponzoni Maurilio , Pattini Linda , Caligaris-Cappio Federico , Ghia Paolo , Brendolan Andrea 
Published: April 2018

AbstractIn chronic lymphocytic leukemia (CLL), the non-hematopoietic stromal microenvironment plays a critical role in promoting tumor cell recruitment, activation, survival, and expansion. However, the nature of the stromal cells and molecular pathways involved remain largely unknown. Here, we demonstrate that leukemic B lymphocytes induce the activation of retinoid acid synthesis and signaling in the microenvironment. Inhibition of RA-signaling in stromal cells causes deregulation of genes associated with adhesion, tissue organization and chemokine secretion including the B-cell chemokine CXCL13. Notably, reducing retinoic acid precursors from the diet or inhibiting RA-signaling through retinoid-antagonist therapy prolong survival by preventing dissemination of leukemia cells into lymphoid tissues. Furthermore, mouse and human leukemia cells could be distinguished from normal B-cells by their increased expression of Rarγ2 and RXRα, respectively. These findings establish a role for retinoids in murine CLL pathogenesis, and provide new therapeutic strategies to target the microenvironment and to control disease progression.
Gut microbiomes of wild great apes fluctuate seasonally in response to diet
Authors: Hicks Allison L. , Lee Kerry Jo , Couto-Rodriguez Mara , Patel Juber , Sinha Rohini , Guo Cheng , Olson Sarah H. , Seimon Anton , Seimon Tracie A. , Ondzie Alain U. , Karesh William B. , Reed Patricia , Cameron Kenneth N. , Lipkin W. Ian , Williams Brent L. 
Published: April 2018

AbstractThe microbiome is essential for extraction of energy and nutrition from plant-based diets and may have facilitated primate adaptation to new dietary niches in response to rapid environmental shifts. Here we use 16S rRNA sequencing to characterize the microbiota of wild western lowland gorillas and sympatric central chimpanzees and demonstrate compositional divergence between the microbiotas of gorillas, chimpanzees, Old World monkeys, and modern humans. We show that gorilla and chimpanzee microbiomes fluctuate with seasonal rainfall patterns and frugivory. Metagenomic sequencing of gorilla microbiomes demonstrates distinctions in functional metabolic pathways, archaea, and dietary plants among enterotypes, suggesting that dietary seasonality dictates shifts in the microbiome and its capacity for microbial plant fiber digestion versus growth on mucus glycans. These data indicate that great ape microbiomes are malleable in response to dietary shifts, suggesting a role for microbiome plasticity in driving dietary flexibility, which may provide fundamental insights into the mechanisms by which diet has driven the evolution of human gut microbiomes.
Frequency-resolved Monte Carlo
Authors: López Carreño Juan Camilo , del Valle Elena , Laussy Fabrice P. 
Published: April 2018

AbstractWe adapt the Quantum Monte Carlo method to the cascaded formalism of quantum optics, allowing us to simulate the emission of photons of known energy. Statistical processing of the photon clicks thus collected agrees with the theory of frequency-resolved photon correlations, extending the range of applications based on correlations of photons of prescribed energy, in particular those of a photon-counting character. We apply the technique to autocorrelations of photon streams from a two-level system under coherent and incoherent pumping, including the Mollow triplet regime where we demonstrate the direct manifestation of leapfrog processes in producing an increased rate of two-photon emission events.
Membrane depolarization and aberrant lipid distributions in the neonatal rat brain following hypoxic-ischaemic insult
Authors: Luptakova Dominika , Baciak Ladislav , Pluhacek Tomas , Skriba Anton , Sediva Blanka , Havlicek Vladimir , Juranek Ivo 
Published: April 2018

AbstractNeonatal hypoxic-ischaemic (HI) encephalopathy is among the most serious complications in neonatology. In the present study, we studied the immediate (0 hour), subacute (36 hours) and late (144 hours) responses of the neonatal brain to experimental HI insult in laboratory rats. At the striatal level, the mass spectrometry imaging revealed an aberrant plasma membrane distribution of Na+/K+ ions in the oedema-affected areas. The failure of the Na+/K+ gradients was also apparent in the magnetic resonance imaging measurements, demonstrating intracellular water accumulation during the acute phase of the HI insult. During the subacute phase, compared with the control brains, an incipient accumulation of an array of N-acylphosphatidylethanolamine (NAPE) molecules was detected in the HI-affected brains, and both the cytotoxic and vasogenic types of oedema were detected. In the severely affected brain areas, abnormal distributions of the monosialogangliosides GM2 and GM3 were observed in two-thirds of the animals exposed to the insult. During the late stage, a partial restoration of the brain tissue was observed in most rats in both the in vivo and ex vivo studies. These specific molecular changes may be further utilized in neonatology practice in proposing and testing novel therapeutic strategies for the treatment of neonatal HI encephalopathy.
Facial bone fragmentation in blind cavefish arises through two unusual ossification processes
Authors: Powers Amanda K. , Kaplan Shane A. , Boggs Tyler E. , Gross Joshua B. 
Published: April 2018

AbstractThe precise mechanisms underlying cranial bone development, evolution and patterning remain incompletely characterised. This poses a challenge to understanding the etiologies of craniofacial malformations evolving in nature. Capitalising on natural variation, “evolutionary model systems” provide unique opportunities to identify underlying causes of aberrant phenotypes as a complement to studies in traditional systems. Mexican blind cavefish are a prime evolutionary model for cranial disorders since they frequently exhibit extreme alterations to the skull and lateral asymmetries. These aberrations occur in stark contrast to the normal cranial architectures of closely related surface-dwelling fish, providing a powerful comparative paradigm for understanding cranial bone formation. Using a longitudinal and in vivo analytical approach, we discovered two unusual ossification processes in cavefish that underlie the development of ‘fragmented’ and asymmetric cranial bones. The first mechanism involves the sporadic appearance of independent bony elements that fail to fuse together later in development. The second mechanism involves the “carving” of channels in the mature bone, a novel form of post-ossification remodeling. In the extreme cave environment, these novel mechanisms may have evolved to augment sensory input, and may indirectly result in a trade-off between sensory expansion and cranial bone development.
Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function
Authors: Perco Paul , Heinzel Andreas , Leierer Johannes , Schneeberger Stefan , Bösmüller Claudia , Oberhuber Rupert , Wagner Silvia , Engler Franziska , Mayer Gert 
Published: April 2018

AbstractDonor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.
Higher order scaffoldin assembly in Ruminococcus flavefaciens cellulosome is coordinated by a discrete cohesin-dockerin interaction
Authors: Bule Pedro , Pires Virgínia M. R. , Alves Victor D. , Carvalho Ana Luísa , Prates José A. M. , Ferreira Luís M. A. , Smith Steven P. , Gilbert Harry J. , Noach Ilit , Bayer Edward A. , Najmudin Shabir , Fontes Carlos M. G. A. 
Published: April 2018

AbstractCellulosomes are highly sophisticated molecular nanomachines that participate in the deconstruction of complex polysaccharides, notably cellulose and hemicellulose. Cellulosomal assembly is orchestrated by the interaction of enzyme-borne dockerin (Doc) modules to tandem cohesin (Coh) modules of a non-catalytic primary scaffoldin. In some cases, as exemplified by the cellulosome of the major cellulolytic ruminal bacterium Ruminococcus flavefaciens, primary scaffoldins bind to adaptor scaffoldins that further interact with the cell surface via anchoring scaffoldins, thereby increasing cellulosome complexity. Here we elucidate the structure of the unique Doc of R. flavefaciens FD-1 primary scaffoldin ScaA, bound to Coh 5 of the adaptor scaffoldin ScaB. The RfCohScaB5-DocScaA complex has an elliptical architecture similar to previously described complexes from a variety of ecological niches. ScaA Doc presents a single-binding mode, analogous to that described for the other two Coh-Doc specificities required for cellulosome assembly in R. flavefaciens. The exclusive reliance on a single-mode of Coh recognition contrasts with the majority of cellulosomes from other bacterial species described to date, where Docs contain two similar Coh-binding interfaces promoting a dual-binding mode. The discrete Coh-Doc interactions observed in ruminal cellulosomes suggest an adaptation to the exquisite properties of the rumen environment.
Cost-effective rapid prototyping and assembly of poly(methyl methacrylate) microfluidic devices
Authors: Matellan Carlos , del Río Hernández Armando E. 
Published: April 2018

AbstractThe difficulty in translating conventional microfluidics from laboratory prototypes to commercial products has shifted research efforts towards thermoplastic materials for their higher translational potential and amenability to industrial manufacturing. Here, we present an accessible method to fabricate and assemble polymethyl methacrylate (PMMA) microfluidic devices in a “mask-less” and cost-effective manner that can be applied to manufacture a wide range of designs due to its versatility. Laser micromachining offers high flexibility in channel dimensions and morphology by controlling the laser properties, while our two-step surface treatment based on exposure to acetone vapour and low-temperature annealing enables improvement of the surface quality without deformation of the device. Finally, we demonstrate a capillarity-driven adhesive delivery bonding method that can produce an effective seal between PMMA devices and a variety of substrates, including glass, silicon and LiNbO3. We illustrate the potential of this technique with two microfluidic devices, an H-filter and a droplet generator. The technique proposed here offers a low entry barrier for the rapid prototyping of thermoplastic microfluidics, enabling iterative design for laboratories without access to conventional microfabrication equipment.
Species contributions to single biodiversity values under-estimate whole community contribution to a wider range of values to society
Authors: Hiron Matthew , Pärt Tomas , Siriwardena Gavin M. , Whittingham Mark J. 
Published: April 2018

AbstractA major task for decision makers is deciding how to consider monetary, cultural and conservation values of biodiversity explicitly when planning sustainable land use. Thus, there is a great need to understand just what “valuing” biodiversity or species really means, e.g. regarding how many and which species are important in providing ecosystem services or other values. Constructing ecosystem-level indices, however, requires weighting the relative contribution of species to the different values. Using farmland birds, we illustrate how species contribute to different biodiversity values, namely utilitarian (pest seed predation potential), cultural (species occurrence in poetry), conservational (declines and rarity) and inherent (all species equal) value. Major contributions to each value are often made by a subset of the community and different species are important for different values, leading to no correlations or, in some cases, negative correlations between species’ relative contributions to different values. Our results and methods using relative contributions of species to biodiversity values can aid decisions when weighing different values in policies and strategies for natural resource management. We conclude that acknowledging the importance of the range of biodiversity values that are apparent from different perspectives is critical if the full value of biodiversity to society is to be realised.
Cerium oxide nanoparticles with antioxidant capabilities and gadolinium integration for MRI contrast enhancement
Authors: Eriksson Peter , Tal Alexey A. , Skallberg Andreas , Brommesson Caroline , Hu Zhangjun , Boyd Robert D. , Olovsson Weine , Fairley Neal , Abrikosov Igor A. , Zhang Xuanjun , Uvdal Kajsa 
Published: April 2018

AbstractThe chelating gadolinium-complex is routinely used as magnetic resonance imaging (MRI) -contrast enhancer. However, several safety issues have recently been reported by FDA and PRAC. There is an urgent need for the next generation of safer MRI-contrast enhancers, with improved local contrast and targeting capabilities. Cerium oxide nanoparticles (CeNPs) are designed with fractions of up to 50% gadolinium to utilize the superior MRI-contrast properties of gadolinium. CeNPs are well-tolerated in vivo and have redox properties making them suitable for biomedical applications, for example scavenging purposes on the tissue- and cellular level and during tumor treatment to reduce in vivo inflammatory processes. Our near edge X-ray absorption fine structure (NEXAFS) studies show that implementation of gadolinium changes the initial co-existence of oxidation states Ce3+ and Ce4+ of cerium, thereby affecting the scavenging properties of the nanoparticles. Based on ab initio electronic structure calculations, we describe the most prominent spectral features for the respective oxidation states. The as-prepared gadolinium-implemented CeNPs are 3–5 nm in size, have r1-relaxivities between 7–13 mM−1 s−1 and show clear antioxidative properties, all of which means they are promising theranostic agents for use in future biomedical applications.
Gene-based analysis of genes related to neurotrophic pathway suggests association of BDNF and VEGFA with antidepressant treatment-response in depressed patients
Authors: Kao Chung-Feng , Liu Yu-Li , Yu Younger W.-Y. , Yang Albert C. , Lin Eugene , Kuo Po-Hsiu , Tsai Shih-Jen 
Published: April 2018

AbstractIt is well established that brain-derived neurotrophic factor (BDNF) signaling pathway plays a key role in the pathophysiology of major depressive disorder (MDD) and in therapeutic mechanisms of antidepressants. We aim to identify genetic vairiants related to MDD susceptibility and antidepressant therapeutic response by using gene-based association analysis with genes related to the neurotrophic pathway. The present study investigated the role of genetic variants in the 10 neurotrophic-related genes (BDNF, NGFR, NTRK2, MTOR, VEGFA, S100A10, SERPINE1, ARHGAP33, GSK3B, CREB1) in MDD susceptibility through a case-control (455 MDD patients and 2,998 healthy controls) study and in antidepressant efficacy (n = 455). Measures of antidepressant therapeutic efficacy were evaluated using the 21-item Hamilton Rating Scale for Depression. Our single-marker and gene-based analyses with ten genes related to the neurotrophic pathway identified 6 polymorphisms that reached a significant level (p-value < 5.0 × 10−3) in both meta- and mega-analyses in antidepressant therapeutic response. One polymorphism was mapped to BDNF and 5 other polymorphisms were mapped to VEGFA. For case-control association study, we found that all of these reported polymorphisms and genes did not reach a suggestive level. The present study supported a role of BDNF and VEGFA variants in MDD therapeutic response.