bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells
Authors: Zheng Jieling , Wang Baiyao , Zheng Rong , Zhang Jian , Huang Chunyue , Zheng Ronghui , Huang Zhong , Qiu Wenze , Liu Mengzhong , Yang Kaijun , Mao Zixu , Ji Aimin , Yuan Yawei 
Published: September 2020

AbstractRadiotherapy is one of the standard treatments for glioma patients; however, its clinical efficacy is limited by radioresistance. We identified a mechanism of such resistance mediated by linc-RA1 (radioresistance-associated long intergenic noncoding RNA 1). Linc-RA1 was upregulated in radioresistant glioma cells and glioma tissue samples, compared with radiosensitive cells and nontumor tissues. Linc-RA1 was associated with inferior overall survival and advanced clinical stage of glioma. Linc-RA1 promoted glioma radioresistance in vitro and in vivo. Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin-specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance. These results reveal that linc-RA1-mediated autophagy is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy in patients with glioma.
c-myc regulates the sensitivity of breast cancer cells to palbociclib via c-myc/miR-29b-3p/CDK6 axis
Authors: Ji Wenfei , Zhang Wenwen , Wang Xin , Shi Yaqin , Yang Fang , Xie Hui , Zhou Wenbin , Wang Shui , Guan Xiaoxiang 
Published: September 2020

AbstractPalbociclib, a CDK4/6 inhibitor, has been granted accelerated approval by US FDA for hormone receptor-positive HER2-negative metastatic breast cancer. To determine potential biomarkers of palbociclib sensitivity to assist in patient selection and clinical development, we investigated the effects of palbociclib in a panel of molecularly characterized breast cancer cell lines. We quantified palbociclib sensitivity and c-myc expression in 11 breast cancer cell lines, 124 breast cancer samples, and The Cancer Genome Atlas database. We found non-TNBC subtypes were more sensitive to palbociclib than TNBC. Activation of c-myc led to differential palbociclib sensitivities, and further inhibition of c-myc enhanced palbociclib sensitivity. Moreover, we identified for the first time a c-myc/miR-29b-3p/CDK6 axis in breast cancer that could be responsible for c-myc-induced palbociclib insensitivity, in which c-myc activation resulted in downregulation of miR-29b-3p, further activated CDK6 and inhibited cell-cycle arrest at G1 phase. Moreover, downregulated (inactived) c-myc-induced oncogenic addiction could increase palbociclib efficacy, using both Xenograft model and patient-derived tumor xenograft (PDTX) model. Our finding extends the concept of combined blockade of the CDK4/6 and c-myc signaling pathways to increase palbociclib sensitivity, making c-myc a promising biomarker for palbociclib sensitivity in breast cancer.
Identification of UBAP1 mutations in juvenile hereditary spastic paraplegia in the 100,000 Genomes Project
Authors: Bourinaris Thomas , Smedley Damian , Cipriani Valentina , Sheikh Isabella , Athanasiou-Fragkouli Alkyoni , Chinnery Patrick , Morris Huw , Real Raquel , Harrison Victoria , Reid Evan , Wood Nicholas ,   Genomics England Research Consortium, Vandrovcova Jana , Houlden Henry , Tucci Arianna 
Published: September 2020

AbstractHereditary spastic paraplegia (HSP) is a group of heterogeneous inherited degenerative disorders characterized by lower limb spasticity. Fifty percent of HSP patients remain yet genetically undiagnosed. The 100,000 Genomes Project (100KGP) is a large UK-wide initiative to provide genetic diagnosis to previously undiagnosed patients and families with rare conditions. Over 400 HSP families were recruited to the 100KGP. In order to obtain genetic diagnoses, gene-based burden testing was carried out for rare, predicted pathogenic variants using candidate variants from the Exomiser analysis of the genome sequencing data. A significant gene-disease association was identified for UBAP1 and HSP. Three protein truncating variants were identified in 13 patients from 7 families. All patients presented with juvenile form of pure HSP, with median age at onset 10 years, showing autosomal dominant inheritance or de novo occurrence. Additional clinical features included parkinsonism and learning difficulties, but their association with UBAP1 needs to be established.
House mouse Mus musculus dispersal in East Eurasia inferred from 98 newly determined complete mitochondrial genome sequences
Authors: Li Yue , Fujiwara Kazumichi , Osada Naoki , Kawai Yosuke , Takada Toyoyuki , Kryukov Alexey P. , Abe Kuniya , Yonekawa Hiromichi , Shiroishi Toshihiko , Moriwaki Kazuo , Saitou Naruya , Suzuki Hitoshi 
Published: September 2020

AbstractThe Eurasian house mouseMus musculusis useful for tracing prehistorical human movement related to the spread of farming. We determined whole mitochondrial DNA (mtDNA) sequences (ca. 16,000 bp) of 98 wild-derived individuals of two subspecies,M.m.musculus(MUS) andM.m.castaneus(CAS). We revealed directional dispersals reaching as far as the Japanese Archipelago from their homelands. Our phylogenetic analysis indicated that the eastward movement of MUS was characterised by five step-wise regional extension events: (1) broad spatial expansion into eastern Europe and the western part of western China, (2) dispersal to the eastern part of western China, (3) dispersal to northern China, (4) dispersal to the Korean Peninsula and (5) colonisation and expansion in the Japanese Archipelago. These events were estimated to have occurred during the last 2000–18,000 years. The dispersal of CAS was characterised by three events: initial divergences (ca. 7000–9000 years ago) of haplogroups in northernmost China and the eastern coast of India, followed by two population expansion events that likely originated from the Yangtze River basin to broad areas of South and Southeast Asia, including Sri Lanka, Bangladesh and Indonesia (ca. 4000–6000 years ago) and to Yunnan, southern China and the Japanese Archipelago (ca. 2000–3500). This study provides a solid framework for the spatiotemporal movement of the human-associated organisms in Holocene Eastern Eurasia using whole mtDNA sequences, reliable evolutionary rates and accurate branching patterns. The information obtained here contributes to the analysis of a variety of animals and plants associated with prehistoric human migration.
Effectiveness of protected areas in conserving tropical forest birds
Authors: Cazalis Victor , Princé Karine , Mihoub Jean-Baptiste , Kelly Joseph , Butchart Stuart H. M. , Rodrigues Ana S. L. 
Published: September 2020

AbstractProtected areas (PAs) are the cornerstones of global biodiversity conservation efforts, but to fulfil this role they must be effective at conserving the ecosystems and species that occur within their boundaries. Adequate monitoring datasets that allow comparing biodiversity between protected and unprotected sites are lacking in tropical regions. Here we use the largest citizen science biodiversity dataset – eBird – to quantify the extent to which protected areas in eight tropical forest biodiversity hotspots are effective at retaining bird diversity. We find generally positive effects of protection on the diversity of bird species that are forest-dependent, endemic to the hotspots, or threatened or Near Threatened, but not on overall bird species richness. Furthermore, we show that in most of the hotspots examined this benefit is driven by protected areas preventing both forest loss and degradation. Our results provide evidence that, on average, protected areas contribute measurably to conserving bird species in some of the world’s most diverse and threatened terrestrial ecosystems.
Climate action requires new accounting guidance and governance frameworks to manage carbon in shelf seas
Authors: Luisetti Tiziana , Ferrini Silvia , Grilli Gaetano , Jickells Timothy D. , Kennedy Hilary , Kröger Silke , Lorenzoni Irene , Milligan Ben , van der Molen Johan , Parker Ruth , Pryce Tim , Turner R. Kerry , Tyllianakis Emmanouil 
Published: September 2020

AbstractAccounting guidelines exist for the recording of carbon flows in terrestrial and coastal ecosystems. Shelf sea sediments, while considered an important carbon store, have yet to receive comparable scrutiny. Here, we explore whether effective management of carbon stocks accumulating in shelf seas could contribute towards a nation’s greenhouse gas emissions reduction targets. We review the complexities of carbon transport and fate in shelf seas, and the geopolitical challenges of carbon accounting in climate governance because of the transboundary nature of carbon flows in the marine environment. New international accounting guidance and governance frameworks are needed to prompt climate action.
NEMF mutations that impair ribosome-associated quality control are associated with neuromuscular disease
Authors: Martin Paige B. , Kigoshi-Tansho Yu , Sher Roger B. , Ravenscroft Gianina , Stauffer Jennifer E. , Kumar Rajesh , Yonashiro Ryo , Müller Tina , Griffith Christopher , Allen William , Pehlivan Davut , Harel Tamar , Zenker Martin , Howting Denise , Schanze Denny , Faqeih Eissa A. , Almontashiri Naif A. M. , Maroofian Reza , Houlden Henry , Mazaheri Neda , Galehdari Hamid , Douglas Ganka , Posey Jennifer E. , Ryan Monique , Lupski James R. , Laing Nigel G. , Joazeiro Claudio A. P. , Cox Gregory A. 
Published: September 2020

AbstractA hallmark of neurodegeneration is defective protein quality control. The E3 ligase Listerin (LTN1/Ltn1) acts in a specialized protein quality control pathway—Ribosome-associated Quality Control (RQC)—by mediating proteolytic targeting of incomplete polypeptides produced by ribosome stalling, and Ltn1 mutation leads to neurodegeneration in mice. Whether neurodegeneration results from defective RQC and whether defective RQC contributes to human disease have remained unknown. Here we show that three independently-generated mouse models with mutations in a different component of the RQC complex, NEMF/Rqc2, develop progressive motor neuron degeneration. Equivalent mutations in yeast Rqc2 selectively interfere with its ability to modify aberrant translation products with C-terminal tails which assist with RQC-mediated protein degradation, suggesting a pathomechanism. Finally, we identify NEMF mutations expected to interfere with function in patients from seven families presenting juvenile neuromuscular disease. These uncover NEMF’s role in translational homeostasis in the nervous system and implicate RQC dysfunction in causing neurodegeneration.
Effects of quercetin-conjugated with superparamagnetic iron oxide nanoparticles on learning and memory improvement through targeting microRNAs/NF-κB pathway
Authors: Ebrahimpour Shiva , Esmaeili Abolghasem , Dehghanian Fariba , Beheshti Siamak 
Published: September 2020

AbstractQuercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) have an ameliorative effect on diabetes-induced memory impairment. The current study aimed to compare the effect of quercetin (QC) and QCSPIONs on inflammation-related microRNAs and NF-κB signaling pathways in the hippocampus of diabetic rats. The expression levels of miR-146a, miR-9, NF-κB, and NF-κB-related downstream genes, including TNF-α, BACE1, AβPP, Bax, and Bcl-2 were measured using quantitative real-time PCR. To determine the NF-κB activity, immunohistochemical expression of NF-κB/p65 phosphorylation was employed. Computer simulated docking analysis also performed to find the QC target proteins involved in the NF-κB pathway. Results indicate that diabetes significantly upregulated the expression levels of miR-146a, miR-9, TNF-α, NF-κB, and subsequently AβPP, BACE1, and Bax. Expression analysis shows that QCSPIONs are more effective than pure QC in reducing the expression of miR-9. Interestingly, QCSPIONs reduce the pathological activity of NF-κB and subsequently normalize BACE1, AβPP, and the ratio of Bax/Bcl-2 expression better than pure QC. Comparative docking analyses also show the stronger binding affinity of QC to IKK and BACE1 proteins compared to specific inhibitors of each protein. In conclusion, our study suggests the potent efficacy of QCSPIONs as a promising drug delivery system in memory improvement through targeting the NF-κB pathway.
A correlation analysis of Light Microscopy and X-ray MicroCT imaging methods applied to archaeological plant remains’ morphological attributes visualization
Authors: Calo Cristina Marilin , Rizzutto Marcia A. , Carmello-Guerreiro Sandra M. , Dias Carlos S. B. , Watling Jennifer , Shock Myrtle P. , Zimpel Carlos A. , Furquim Laura P. , Pugliese Francisco , Neves Eduardo G. 
Published: September 2020

AbstractIn this work, several attributes of the internal morphology of drupaceous fruits found in the archaeological site Monte Castelo (Rondonia, Brazil) are analyzed by means of two different imaging methods. The aim is to explore similarities and differences in the visualization and analytical properties of the images obtained via High Resolution Light Microscopy and X-ray micro-computed tomography (X-ray MicroCT) methods. Both provide data about the three-layered pericarp (exo-, meso- and endocarp) of the studied exemplars, defined by cell differentiation, vascularisation, cellular contents, presence of sclerenchyma cells and secretory cavities. However, it is possible to identify a series of differences between the information that can be obtained through each of the methods. These variations are related to the definition of contours and fine details of some characteristics, their spatial distribution, size attributes, optical properties and material preservation. The results obtained from both imaging methods are complementary, contributing to a more exhaustive morphological study of the plant remains. X-ray MicroCT in phase-contrast mode represents a suitable non-destructive analytic technique when sample preservation is required.
The effects of anxiety and dual-task on upper limb motor control of chronic stroke survivors
Authors: Hejazi-Shirmard Mahnaz , Lajevardi Laleh , Rassafiani Mehdi , Taghizadeh Ghorban 
Published: September 2020

AbstractThis study was designed to investigate the effects of anxiety and dual-task on reach and grasp motor control in chronic stroke survivors compared with age- and sex-matched healthy subjects (HC). Reach and grasp kinematic data of 68 participants (high-anxiety stroke (HA-stroke), n = 17; low-anxiety stroke (LA-stroke), n = 17; low-anxiety HC, n = 17; and high-anxiety HC, n = 17) were recorded under single- and dual-task conditions. Inefficient reach and grasp of stroke participants, especially HA-stroke were found compared with the control groups under single- and dual-task conditions as evidenced by longer movement time (MT), lower and earlier peak velocity (PV) as well as delayed and smaller hand opening. The effects of dual-task on reach and grasp kinematic measures were similar between HCs and stroke participants (i.e., increased MT, decreased PV that occurred earlier, and delayed and decreased hand opening), with greater effect in stroke groups than HCs, and in HA-stroke group than LA-stroke group. The results indicate that performing a well-learned upper limb movement with concurrent cognitive task leads to decreased efficiency of motor control in chronic stroke survivors compared with HCs. HA-stroke participants were more adversely affected by challenging dual-task conditions, underlying importance of assessing anxiety and designing effective interventions for it in chronic stroke survivors.
Theoretical analysis of a circular hybrid plasmonic waveguide to design a hybrid plasmonic nano-antenna
Authors: Khodadadi Maryam , Nozhat Najmeh , Moshiri Seyyed Mohammad Mehdi 
Published: September 2020

AbstractIn this paper, a circular hybrid plasmonic waveguide-fed nano-antenna (CHPWFNA) has been introduced for operating at the standard telecommunication wavelength of 1,550 nm. For the first time, the dispersion relation of a circular hybrid plasmonic waveguide as the feed line of the proposed nano-antenna has been derived, analytically. To verify the accuracy of the analytical solution, two numerical techniques of finite element method (FEM) and finite-difference time-domain (FDTD) method have been used. Numerical results are well-matched with the theoretical ones. The characteristics of the CHPWFNA have been studied by two mentioned methods. The obtained realized gains (directivities) by the FDTD and FEM simulations are 9.03 dB (9.38 dBi) and 10.00 dB (10.32 dBi), respectively, at 1,550 nm wavelength. For on-chip point-to-point wireless link performance, the obtained quality factor by the FDTD method (FEM) is 63.97 (100). The obtained radiation characteristics and link performance reveal that at 1,550 nm, the proposed antenna has the best performance. Besides, the frequency bandwidth of the antenna (185–200 THz) covers the low-loss optical frequency range. Also, paying attention to the laser eye safety is so important. Consequently, the wavelength of 1,550 nm has been chosen as the target wavelength. Moreover, the array configuration has been studied and the directivity and realized gain have been obtained based on the array factor theory and numerical methods, which are agree with each other. The attained realized gain by the FDTD method (FEM) for the considered single row array, at 1,550 nm, is 11.20 dB (11.30 dB). There is a little difference between the numerical results due to the total mesh size, the grid size refinement and the relative error of the numerical methods convergence. Finally, as one of the most important challenges in fabrication is the gold surface quality, we have studied the effect of gold surface roughness and its pentagonal cross section on the antenna performance.
Semaphorin 3A controls enteric neuron connectivity and is inversely associated with synapsin 1 expression in Hirschsprung disease
Authors: Gonzales Jacques , Le Berre-Scoul Catherine , Dariel Anne , Bréhéret Paul , Neunlist Michel , Boudin Hélène 
Published: September 2020

AbstractMost of the gut functions are controlled by the enteric nervous system (ENS), a complex network of enteric neurons located throughout the wall of the gastrointestinal tract. The formation of ENS connectivity during the perinatal period critically underlies the establishment of gastrointestinal motility, but the factors involved in this maturation process remain poorly characterized. Here, we examined the role of Semaphorin 3A (Sema3A) on ENS maturation and its potential implication in Hirschsprung disease (HSCR), a developmental disorder of the ENS with impaired colonic motility. We found that Sema3A and its receptor Neuropilin 1 (NRP1) are expressed in the rat gut during the early postnatal period. At the cellular level, NRP1 is expressed by enteric neurons, where it is particularly enriched at growth areas of developing axons. Treatment of primary ENS cultures and gut explants with Sema3A restricts axon elongation and synapse formation. Comparison of the ganglionic colon of HSCR patients to the colon of patients with anorectal malformation shows reduced expression of the synaptic molecule synapsin 1 in HSCR, which is inversely correlated with Sema3A expression. Our study identifies Sema3A as a critical regulator of ENS connectivity and provides a link between altered ENS connectivity and HSCR.
Network science characteristics of brain-derived neuronal cultures deciphered from quantitative phase imaging data
Authors: Yin Chenzhong , Xiao Xiongye , Balaban Valeriu , Kandel Mikhail E. , Lee Young Jae , Popescu Gabriel , Bogdan Paul 
Published: September 2020

AbstractUnderstanding the mechanisms by which neurons create or suppress connections to enable communication in brain-derived neuronal cultures can inform how learning, cognition and creative behavior emerge. While prior studies have shown that neuronal cultures possess self-organizing criticality properties, we further demonstrate that in vitro brain-derived neuronal cultures exhibit a self-optimization phenomenon. More precisely, we analyze the multiscale neural growth data obtained from label-free quantitative microscopic imaging experiments and reconstruct the in vitro neuronal culture networks (microscale) and neuronal culture cluster networks (mesoscale). We investigate the structure and evolution of neuronal culture networks and neuronal culture cluster networks by estimating the importance of each network node and their information flow. By analyzing the degree-, closeness-, and betweenness-centrality, the node-to-node degree distribution (informing on neuronal interconnection phenomena), the clustering coefficient/transitivity (assessing the “small-world” properties), and the multifractal spectrum, we demonstrate that murine neurons exhibit self-optimizing behavior over time with topological characteristics distinct from existing complex network models. The time-evolving interconnection among murine neurons optimizes the network information flow, network robustness, and self-organization degree. These findings have complex implications for modeling neuronal cultures and potentially on how to design biological inspired artificial intelligence.
Males and females exhibit distinct relationships between intervertebral disc degeneration and pain in a rat model
Authors: Mosley Grace E. , Wang Minghui , Nasser Philip , Lai Alon , Charen Daniel A. , Zhang Bin , Iatridis James C. 
Published: September 2020

AbstractBack pain is linked to intervertebral disc (IVD) degeneration, but clinical studies show the relationship is complex. This study assessed whether males and females have distinct relationships between IVD degeneration and pain using an in vivo rat model. Forty-eight male and female Sprague–Dawley rats had lumbar IVD puncture or sham surgery. Six weeks after surgery, IVDs were evaluated by radiologic IVD height, histological grading, and biomechanical testing. Pain was assessed by von Frey assay and dorsal root ganglia (DRG) expression ofCalcaandTac1genes. Network analysis visualized which measures of IVD degeneration most related to pain by sex. In both females and males, annular puncture induced structural IVD degeneration, but functional biomechanical properties were similar to sham. Females and males had distinct differences in mechanical allodynia and DRG gene expression, even though sex differences in IVD measurements were limited. Network analysis also differed by sex, with more associations between annular puncture injury and pain in the male network. Sex differences exist in the interactions between IVD degeneration and pain. Limited correlation between measures of pain and IVD degeneration highlights the need to evaluate pain or nociception in IVD degeneration models to better understand nervous system involvement in discogenic pain.