bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Software‐Defined Multichannel Receiver for EAR
Authors: M. Aris N. A. , Hashiguchi H. , Yamamoto M. 
Published: July 2019

AbstractThe Equatorial Atmosphere Radar (EAR) is a very high frequency Doppler radar operated with an active phased‐array antenna system at 47 MHz. It is located at the equator in Kototabang, West Sumatra, Indonesia (0.20°S, 100.32°E) and was established with a single receiving channel. Here, we present the development of a multichannel receiver system for EAR using a combination of the Universal Software Radio Peripheral X300 (USRP X300) series and GNU Radio software. Two USRP X300 devices, corresponding to four receiving channels, were synchronized using 10‐MHz reference clocks and a one‐pulse per second signal. Received signals were collected by the existing EAR antennas, fed to the USRPs for digital conversion, and then stored on a hard disk drive. Signal postprocessing was carried out to estimate wind velocity profiles. Wind profiles estimated using full correlation analysis indicate that the spaced antenna method from multichannel receivers agrees well with EAR standard observational data.
IFITM3 promotes bone metastasis of prostate cancer cells by mediating activation of the TGF-β signaling pathway
Authors: Liu Xi , Chen Lu , Fan Yinghui , Hong Yi , Yang Xiaoqun , Li Yao , Lu Jianlei , Lv Jianmin , Pan Xiuwu , Qu Fajun , Cui Xingang , Gao Yi , Xu Danfeng 
Published: July 2019

AbstractAdvanced-stage prostate cancer (PCa) is often diagnosed with bone metastasis, for which there are limited therapies. Transforming growth factor β (TGF-β) is known to induce epithelial–mesenchymal transition (EMT), and abundance of TGF-β in the bone matrix is one of the important growth factors contributing to bone metastasis. TGF-β is reported as a key mediator of bone metastasis, but the underlying mechanism has not been elucidated. It was found in our study that Interferon-inducible Transmembrane Protein 3 (IFITM3) played a key role in the regulation of malignant tumor cell proliferation, invasion, and bone migration by binding to Smad4, thus activating the TGF-β-Smads Signaling Pathway. Lentivirus-mediated short hairpin RNA (shRNA) knockdown of IFITM3 inhibited cell proliferation and colony formation, induced apoptosis and inhibited migration by reversing EMT and downregulating the expression of metastasis-related molecules including FGFs and PTHrP. Microarray analysis showed that IFITM3 knockdown could alter the MAPK pathway associated with TGF-β-Smads signaling. By knocking down and overexpressing IFITM3, we demonstrated that IFITM3 expression level had an effect on MAPK pathway activation, and this change was more pronounced upon exogenous TGF-β stimulation. These results suggest that IFITM3 played an oncogenic role in PCa progression and bone metastasis via a novel TGF-β-Smads-MAPK pathway.
Real-time manipulation of intestinal peristalsis by enteric-encapsulated magnetic nanoparticles & wearable 3D-printed devices
Authors: Yu Fen , Cui Xiao , Lang Yuanyuan , Huang Fei , Wang Lingfang , Miao Xinxin , Ai Fanrong , Xie Caifeng , Xin Hongbo , Yang Cheng , Wang Xiaolei 
Published: July 2019

AbstractThe present study introduced a new biomedical engineering concept to realize the real-time adjustment of nutrient absorption. With the aid of a 3D-printed wearable external magnet device, both the location and vibration of enteric-coated magnetic nanoparticles (EMNPs) in the small intestine could be controlled directly. Through a facile mobile app, gastrointestinal motility could be monitored directly in real time. Further tests revealed that this technology could be an attractive way to adjust one’s weight without diet or exercise modification.
Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues
Authors: Glaser Adam K. , Reder Nicholas P. , Chen Ye , Yin Chengbo , Wei Linpeng , Kang Soyoung , Barner Lindsey A. , Xie Weisi , McCarty Erin F. , Mao Chenyi , Halpern Aaron R. , Stoltzfus Caleb R. , Daniels Jonathan S. , Gerner Michael Y. , Nicovich Philip R. , Vaughan Joshua C. , True Lawrence D. , Liu Jonathan T. C. 
Published: July 2019

AbstractRecent advances in optical clearing and light-sheet microscopy have provided unprecedented access to structural and molecular information from intact tissues. However, current light-sheet microscopes have imposed constraints on the size, shape, number of specimens, and compatibility with various clearing protocols. Here we present a multi-immersion open-top light-sheet microscope that enables simple mounting of multiple specimens processed with a variety of clearing protocols, which will facilitate wide adoption by preclinical researchers and clinical laboratories. In particular, the open-top geometry provides unsurpassed versatility to interface with a wide range of accessory technologies in the future.
Poly(ADP-ribose) polymerase-1 antagonizes DNA resection at double-strand breaks
Authors: Caron Marie-Christine , Sharma Ajit K. , O’Sullivan Julia , Myler Logan R. , Ferreira Maria Tedim , Rodrigue Amélie , Coulombe Yan , Ethier Chantal , Gagné Jean-Philippe , Langelier Marie-France , Pascal John M. , Finkelstein Ilya J. , Hendzel Michael J. , Poirier Guy G. , Masson Jean-Yves 
Published: July 2019

AbstractPARP-1 is rapidly recruited and activated by DNA double-strand breaks (DSBs). Upon activation, PARP-1 synthesizes a structurally complex polymer composed of ADP-ribose units that facilitates local chromatin relaxation and the recruitment of DNA repair factors. Here, we identify a function for PARP-1 in DNA DSB resection. Remarkably, inhibition of PARP-1 leads to hyperresected DNA DSBs. We show that loss of PARP-1 and hyperresection are associated with loss of Ku, 53BP1 and RIF1 resection inhibitors from the break site. DNA curtains analysis show that EXO1-mediated resection is blocked by PARP-1. Furthermore, PARP-1 abrogation leads to increased DNA resection tracks and an increase of homologous recombination in cellulo. Our results, therefore, place PARP-1 activation as a critical early event for DNA DSB repair activation and regulation of resection. Hence, our work has direct implications for the clinical use and effectiveness of PARP inhibition, which is prescribed for the treatment of various malignancies.
Bone-targeting AAV-mediated silencing of Schnurri-3 prevents bone loss in osteoporosis
Authors: Yang Yeon-Suk , Xie Jun , Wang Dan , Kim Jung-Min , Tai Phillip W. L. , Gravallese Ellen , Gao Guangping , Shim Jae-Hyuck 
Published: July 2019

AbstractRNAi-based bone anabolic gene therapy has demonstrated initial success, but many practical challenges are still unmet. Here, we demonstrate that a recombinant adeno-associated virus 9 (rAAV9) is highly effective for transducing osteoblast lineage cells in the bone. The adaptor protein Schnurri-3 (SHN3)is a promising therapeutic target for osteoporosis, as deletion ofshn3prevents bone loss in osteoporotic mice and short-term inhibition ofshn3in adult mice increases bone mass. Accordingly, systemic and direct joint administration of an rAAV9 vector carrying an artificial-microRNA that targetsshn3(rAAV9-amiR-shn3) in mice markedly enhanced bone formation via augmented osteoblast activity. Additionally, systemic delivery of rAAV9-amiR-shn3in osteoporotic mice counteracted bone loss and enhanced bone mechanical properties. Finally, we rationally designed a capsid that exhibits improved specificity to bone by grafting the bone-targeting peptide motif (AspSerSer)6onto the AAV9-VP2 capsid protein. Collectively, our results identify a bone-targeting rAAV-mediated gene therapy for osteoporosis.
Astrocytic p38α MAPK drives NMDA receptor-dependent long-term depression and modulates long-term memory
Authors: Navarrete Marta , Cuartero María I. , Palenzuela Rocío , Draffin Jonathan E. , Konomi Ainoa , Serra Irene , Colié Sandra , Castaño-Castaño Sergio , Hasan Mazahir T. , Nebreda Ángel R. , Esteban José A. 
Published: July 2019

AbstractNMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. The core mechanism for this form of plasticity is thought to be entirely neuronal. However, we now demonstrate that astrocytic activity drives LTD at CA3-CA1 synapses. We have found that LTD induction enhances astrocyte-to-neuron communication mediated by glutamate, and that Ca2+ signaling and SNARE-dependent vesicular release from the astrocyte are required for LTD expression. In addition, using optogenetic techniques, we show that low-frequency astrocytic activation, in the absence of presynaptic activity, is sufficient to induce postsynaptic AMPA receptor removal and LTD expression. Using cell-type-specific gene deletion, we show that astrocytic p38α MAPK is required for the increased astrocytic glutamate release and astrocyte-to-neuron communication during low-frequency stimulation. Accordingly, removal of astrocytic (but not neuronal) p38α abolishes LTD expression. Finally, this mechanism modulates long-term memory in vivo.
Mutations in SMARCB1 and in other Coffin–Siris syndrome genes lead to various brain midline defects
Authors: Filatova Alina , Rey Linda K. , Lechler Marion B. , Schaper Jörg , Hempel Maja , Posmyk Renata , Szczaluba Krzysztof , Santen Gijs W. E. , Wieczorek Dagmar , Nuber Ulrike A. 
Published: July 2019

AbstractMutations in genes encoding components of BAF (BRG1/BRM-associated factor) chromatin remodeling complexes cause neurodevelopmental disorders and tumors. The mechanisms leading to the development of these two disease entities alone or in combination remain unclear. We generated mice with a heterozygous nervous system-specific partial loss-of-function mutation in a BAF core component gene, Smarcb1. These Smarcb1 mutant mice show various brain midline abnormalities that are also found in individuals with Coffin–Siris syndrome (CSS) caused by SMARCB1, SMARCE1, and ARID1B mutations and in SMARCB1-related intellectual disability (ID) with choroid plexus hyperplasia (CPH). Analyses of the Smarcb1 mutant animals indicate that one prominent midline abnormality, corpus callosum agenesis, is due to midline glia aberrations. Our results establish a novel role of Smarcb1 in the development of the brain midline and have important clinical implications for BAF complex-related ID/neurodevelopmental disorders.
Facilitating the transmetalation step with aryl-zincates in nickel-catalyzed enantioselective arylation of secondary benzylic halides
Authors: Huang Weichen , Hu Mei , Wan Xiaolong , Shen Qilong 
Published: July 2019

AbstractNickel-catalyzed asymmetric cross-coupling of secondary alkyl electrophiles with different nucleophiles represents a powerful strategy for the construction of chiral tertiary carbon centers. Yet, the use of aryl Grignard reagents or aryl zinc halides in many reactions typically resulted in low enantioselectivity, mainly due to their slow transmetalation step in the catalytical cycle and consequently the requirement of relatively high temperature. Here we report that the use of lithium aryl zincate [Ph2ZnBr]Li facilitates the transmetalation step of the nickel-catalyzed cross-coupling reaction. Based on this discovery, a highly enantioselective construction of fluoroalkyl-substituted stereogenic center by a nickel-catalyzed asymmetric Suzuki-Miyaura coupling of α-bromobenzyl trifluoro-/difluoro-/mono- fluoromethanes with a variety of lithium aryl zincates [Ph2ZnBr]Li that were in situ generated from the reaction of lithium organoboronate with 1.0 equivalent of ZnBr2 was described.
miR-103/107 prolong Wnt/β-catenin signaling and colorectal cancer stemness by targeting Axin2
Authors: Chen Hsin-Yi , Lang Yaw-Dong , Lin Han-Nan , Liu Yun-Ru , Liao Chun-Chieh , Nana André Wendindondé , Yen Yun , Chen Ruey-Hwa 
Published: July 2019

AbstractCancer stemness drives tumor initiation, progression, metastasis, recurrence, and therapy resistance. However, mechanisms that potentiate the acquisition and maintenance of stemness fate of cancer cells remain incompletely understood. Here, we show that miR-103/107 stimulate multiple stem-like features in colorectal cancer, including expression of stem-like markers, appearance of side-population cells, and capabilities in self-renewal, tumor initiation, recurrence, and chemoresistance. Mechanistically, these stemness-promoting functions are mediated by miR-103/107-dependent repression of Axin2, a negative feedback regulator of Wnt/β-catenin signaling. Through inhibiting Axin2, miR-103/107 trigger a prolonged duration of Wnt/β-catenin signaling and a sustained induction of Wnt responsive genes. In colorectal cancer patients, miR-103/107 expression correlates inversely with Axin2 expression and a signature of miR-103/107 high and Axin2 low expression profile correlates with poor prognosis. Together, our study identifies a novel function of miR-103/107 in promoting colorectal cancer stemness by targeting Axin2 and elucidates the clinical relevance and prognostic value of this axis in colorectal cancer.
All-Male Groups in Asian Elephants: A Novel, Adaptive Social Strategy in Increasingly Anthropogenic Landscapes of Southern India
Authors: Srinivasaiah Nishant , Kumar Vinod , Vaidyanathan Srinivas , Sukumar Raman , Sinha Anindya 
Published: July 2019

AbstractMale Asian elephants are known to adopt a high-risk high-gain foraging strategy by venturing into agricultural areas and feeding on nutritious crops in order to improve their reproductive fitness. We hypothesised that the high risks to survival posed by increasingly urbanising and often unpredictable production landscapes may necessitate the emergence of behavioural strategies that allow male elephants to persist in such landscapes. Using 1445 photographic records of 248 uniquely identified male Asian elephants over a 23-month period, we show that male Asian elephants display striking emergent behaviour, particularly the formation of stable, long-term all-male groups, typically in non-forested or human-modified and highly fragmented areas. They remained solitary or associated in mixed-sex groups, however, within forested habitats. These novel, large all-male associations, may constitute a unique life history strategy for male elephants in the high-risk but resource-rich production landscapes of southern India. This may be especially true for the adolescent males, which seemed to effectively improve their body condition by increasingly exploiting anthropogenic resources when in all-male groups. This observation further supports our hypothesis that such emergent behaviours are likely to constitute an adaptive strategy for male Asian elephants that may be forced to increasingly confront anthropogenically intrusive environments.
Drought modulates interactions between arbuscular mycorrhizal fungal diversity and barley genotype diversity
Authors: Sendek Agnieszka , Karakoç Canan , Wagg Cameron , Domínguez-Begines Jara , do Couto Gabriela Martucci , van der Heijden Marcel G. A. , Naz Ali Ahmad , Lochner Alfred , Chatzinotas Antonis , Klotz Stefan , Gómez-Aparicio Lorena , Eisenhauer Nico 
Published: July 2019

AbstractDroughts associated with climate change alter ecosystem functions, especially in systems characterized by low biodiversity, such as agricultural fields. Management strategies aimed at buffering climate change effects include the enhancement of intraspecific crop diversity as well as the diversity of beneficial interactions with soil biota, such as arbuscular mycorrhizal fungi (AMF). However, little is known about reciprocal relations of crop and AMF diversity under drought conditions. To explore the interactive effects of plant genotype richness and AMF richness on plant yield under ambient and drought conditions, we established fully crossed diversity gradients in experimental microcosms. We expected highest crop yield and drought tolerance at both high barley and AMF diversity. While barley richness and AMF richness altered the performance of both barley and AMF, they did not mitigate detrimental drought effects on the plant and AMF. Root biomass increased with mycorrhiza colonization rate at high AMF richness and low barley richness. AMF performance increased under higher richness of both barley and AMF. Our findings indicate that antagonistic interactions between barley and AMF may occur under drought conditions, particularly so at higher AMF richness. These results suggest that unexpected alterations of plant-soil biotic interactions could occur under climate change.
Validity of pervasive computing based continuous physical activity assessment in community-dwelling old and oldest-old
Authors: Schütz Narayan , Saner Hugo , Rudin Beatrice , Botros Angela , Pais Bruno , Santschi Valérie , Buluschek Philipp , Gatica-Perez Daniel , Urwyler Prabitha , Marchal-Crespo Laura , Müri René M. , Nef Tobias 
Published: July 2019

AbstractIn older adults, physical activity is crucial for healthy aging and associated with numerous health indicators and outcomes. Regular assessments of physical activity can help detect early health-related changes and manage physical activity targeted interventions. The quantification of physical activity, however, is difficult as commonly used self-reported measures are biased and rather unprecise point in time measurements. Modern alternatives are commonly based on wearable technologies which are accurate but suffer from usability and compliance issues. In this study, we assessed the potential of an unobtrusive ambient-sensor based system for continuous, long-term physical activity quantification. Towards this goal, we analysed one year of longitudinal sensor- and medical-records stemming from thirteen community-dwelling old and oldest old subjects. Based on the sensor data the daily number of room-transitions as well as the raw sensor activity were calculated. We did find the number of room-transitions, and to some degree also the raw sensor activity, to capture numerous known associations of physical activity with cognitive, well-being and motor health indicators and outcomes. The results of this study indicate that such low-cost unobtrusive ambient-sensor systems can provide an adequate approximation of older adults’ overall physical activity, sufficient to capture relevant associations with health indicators and outcomes.
Demography of avian scavengers after Pleistocene megafaunal extinction
Authors: Perrig Paula L. , Fountain Emily D. , Lambertucci Sergio A. , Pauli Jonathan N. 
Published: July 2019

AbstractThe late Quaternary megafauna extinctions reshaped species assemblages, yet we know little about how extant obligate scavengers responded to this abrupt ecological change. To explore whether obligate scavengers persisted by depending on contemporary community linkages or via foraging flexibility, we tested the importance of the trophic interaction between pumas (Puma concolor) and native camelids (Vicugna vicugnaandLama guanicoe) for the persistence of Andean condors (Vultur gryphus) in southern South America, and compared the demographic history of three vultures in different continents. We sequenced and compiled mtDNA to reconstruct past population dynamics. Our results suggest that Andean condors increased in population size >10 KYA, whereas vicuñas and pumas showed stable populations and guanacos a recent (<10 KYA) demographic expansion, suggesting independent trajectories between species. Further, vultures showed positive demographic trends: white-backed vultures (Gyps africanus) increased in population size, matching attenuated community changes in Africa, and California condors (Gymnogyps californianus) exhibited a steep demographic expansion ~20 KYA largely concurrent with North American megafaunal extinctions. Our results suggest that dietary plasticity of extant vulture lineages allowed them to thrive despite historical environmental changes. This dietary flexibility, however, is now detrimental as it enhances risk to toxicological compounds harbored by modern carrion resources.
A unique ~12 ka subaerial record of rift-transform triple-junction tectonics, NE Iceland
Authors: Rust Derek , Whitworth Malcolm 
Published: July 2019

AbstractIn northern Iceland the European-North American plate boundary is broad and complex but includes a remarkable subaerial triple-junction intersection between the Husavik-Flatey Fault (HFF) dextral transform and rifting in the Northern Volcanic Zone. Fortuitously, the triple junction occurs in a sheet of ~12 ka pahoehoe lavas; a tabula rasa recording innumerable fault features displayed in exquisite detail. High-resolution drone imagery, coupled with 120 field measurements of fault slip directions and opening amounts, made possible the mapping and analysis of this detail and, importantly, enabled recognition and exclusion of potentially misleading primary deformation features associated with emplacement of the lavas. Rift-transform interactions in this natural laboratory have remained spatially stable throughout post-glacial time, although with transform-affinity faults reactivated to accommodate rift extension and transform ‘encroachment’ into the rift domain. First-order en-echelon Riedel fault complexes are recognised, linked by transpressional faulting and compressional strike-slip relay ramps, as well as second-order R shears, R’ and P shears, and previously undescribed R’ Riedel-in-Riedel relationships. A pahoehoe flow front offset along a first-order Riedel fault complex records slip at ~3.8 mm a−1, which may be consistent with the published GPS-based current slip-rate estimate of ~6.8 mm a−1 across the HFF as a whole.
Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type 2 diabetes
Authors: Diamanti Klev , Cavalli Marco , Pan Gang , Pereira Maria J. , Kumar Chanchal , Skrtic Stanko , Grabherr Manfred , Risérus Ulf , Eriksson Jan W. , Komorowski Jan , Wadelius Claes 
Published: July 2019

AbstractType 2 diabetes (T2D) mellitus is a complex metabolic disease commonly caused by insulin resistance in several tissues. We performed a matched two-dimensional metabolic screening in tissue samples from 43 multi-organ donors. The intra-individual analysis was assessed across five key metabolic tissues (serum, visceral adipose tissue, liver, pancreatic islets and skeletal muscle), and the inter-individual across three different groups reflecting T2D progression. We identified 92 metabolites differing significantly between non-diabetes and T2D subjects. In diabetes cases, carnitines were significantly higher in liver, while lysophosphatidylcholines were significantly lower in muscle and serum. We tracked the primary tissue of origin for multiple metabolites whose alterations were reflected in serum. An investigation of three major stages spanning from controls, to pre-diabetes and to overt T2D indicated that a subset of lysophosphatidylcholines was significantly lower in the muscle of pre-diabetes subjects. Moreover, glycodeoxycholic acid was significantly higher in liver of pre-diabetes subjects while additional increase in T2D was insignificant. We confirmed many previously reported findings and substantially expanded on them with altered markers for early and overt T2D. Overall, the analysis of this unique dataset can increase the understanding of the metabolic interplay between organs in the development of T2D.