bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increase in HDAC9 suppresses myoblast differentiation via epigenetic regulation of autophagy in hypoxia
Authors: Zhang Zhang , Zhang Liqiang , Zhou You , Li Liya , Zhao Jiangdong , Qin Wen , Jin Zuolin , Liu Wenjia 
Published: July 2019

AbstractExtremely reduced oxygen (O2) levels are detrimental to myogenic differentiation and multinucleated myotube formation, and chronic exposure to high-altitude hypoxia has been reported to be an important factor in skeletal muscle atrophy. However, how chronic hypoxia causes muscle dysfunction remains unknown. In the present study, we found that severe hypoxia (1% O2) significantly inhibited the function of C2C12 cells (from a myoblast cell line). Importantly, the impairment was continuously manifested even during culture under normoxic conditions for several passages. Mechanistically, we revealed that histone deacetylases 9 (HDAC9), a member of the histone deacetylase family, was significantly increased in C2C12 cells under hypoxic conditions, thereby inhibiting intracellular autophagy levels by directly binding to the promoter regions of Atg7, Beclin1, and LC3. This phenomenon resulted in the sequential dephosphorylation of GSK3β and inactivation of the canonical Wnt pathway, impairing the function of the C2C12 cells. Taken together, our results suggest that hypoxia-induced myoblast dysfunction is due to aberrant epigenetic regulation of autophagy, and our experimental evidence reveals the possible molecular pathogenesis responsible for some muscle diseases caused by chronic hypoxia and suggests a potential therapeutic option.
PLPP/CIN-mediated NEDD4-2 S448 dephosphorylation regulates neuronal excitability via GluA1 ubiquitination
Authors: Kim Ji-Eun , Lee Duk-Shin , Kim Min Ju , Kang Tae-Cheon 
Published: July 2019

AbstractNeuronal precursor cell expressed developmentally downregulated 4-2 (NEDD4-2) is an E3 ubiquitin ligase to regulate ion transport by controlling cellular trafficking/endocytosis and lysosomal degradation of ion channels and transporters. Thus, NEDD4-2 is relevant to neuronal excitability and epileptic encephalopathies in human patients. However, the regulatory molecules for NEDD4-2 dephosphorylation have been still elusive. Here, we demonstrate that pyridoxal-5′-phosphate phosphatase/chronophin (PLPP/CIN) specifically dephosphorylated NEDD4-2 serine (S) 448 site. PLPP/CIN deletion inhibited NEDD4-2 ubiquitination, and diminished the responsiveness of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) by facilitating NEDD4-2-mediated ubiquitination of GluA1 subunit under physiological condition. PLPP/CIN overexpression reversed these effects. These PLPP/CIN-mediated processes were required for the increased seizure severity and its progression in response to kainic acid (KA). Therefore, we suggest the novel function of PLPP/CIN as a NEDD4-2 phosphatase, which may be a potential therapeutic target for NEDD4-2-associated diseases as well as various neurological and psychiatric disorders, including epilepsy.
The natural compound neobractatin inhibits tumor metastasis by upregulating the RNA-binding-protein MBNL2
Authors: Zhang Juan , Zheng Zhaoqing , Wu Man , Zhang Li , Wang Jing , Fu Wenwei , Xu Naihan , Zhao Zhili , Lao Yuanzhi , Xu Hongxi 
Published: July 2019

AbstractTumor metastasis is the predominant cause of lethality in cancer. We found that Neobractatin (NBT), a natural compound isolated from Garcinia bracteata, could efficiently inhibit breast and lung cancer cells metastasis. However, the mechanisms of NBT inhibiting cancer metastasis remain unclear. Based on the RNA-sequencing result and transcriptome analysis, Muscleblind-like 2 (MBNL2) was found to be significantly upregulated in the cells treated with NBT. The Cancer Genome Atlas (TCGA) database analysis indicated that the expression of MBNL2 in breast and lung carcinoma tumor tissues was significantly lower compared to normal tissues. We thus conducted to investigate the antimetastatic role of MBNL2. MBNL2 overexpression mimicked the effect of NBT on breast cancer and lung cancer cell motility and metastasis, in addition significantly enhanced the inhibition effect of NBT. MBNL2 knockdown furthermore partially eliminated the inhibitory effect of NBT on metastasis. Mechanistically, we demonstrated that NBT- and MBNL2-mediated antimetastasis regulation significantly correlated with the pAKT/epithelial-mesenchymal transition (EMT) pathway. Subsequent in vivo study showed the same metastasis inhibition effect in NBT and MBNL2 in MDA-MB-231 xenografts mouse model. This study suggest that NBT possesses significant antitumor activity in breast and lung cancer cells that is partly mediated through the MBNL2 expression and enhancement in metastasis via the pAKT/EMT signaling pathway.
Free-standing and ultrathin inorganic light-emitting diode array
Authors: Tchoe Youngbin , Chung Kunook , Lee Keundong , Jo Janghyun , Chung Kyungmin , Hyun Jerome K. , Kim Miyoung , Yi Gyu-Chul 
Published: July 2019

AbstractWe report on the fabrication and characteristics of an individually addressable gallium nitride (GaN) microdisk light-emitting diode (LED) array in free-standing and ultrathin form. A high-quality GaN microdisk array with n-GaN, InGaN/GaN quantum wells and p-GaN layers was epitaxially grown on graphene microdots patterned on SiO2/Si substrates. Due to the weak attachment of the graphene microdots to the growth substrate, a microdisk array coated with a polyimide layer was easily separated from the substrate using mechanical or chemical methods to form an ultrathin free-standing film. Individually addressable microdisk LEDs were created by forming thin metal contacts on the p-GaN and n-GaN surfaces in a crossbar configuration. Each microdisk LED that comprised an ultrahigh resolution array of 2500 pixels per inch was found to be uniquely addressable. The devices in free-standing form exhibited stable electrical and optoelectronic characteristics under extreme bending conditions and continuous operation mode despite the absence of a heat dissipating substrate. These results present promising approaches for the fabrication of high-quality inorganic semiconductor devices for ultrahigh resolution and high-performance flexible applications.
PRKCSH contributes to tumorigenesis by selective boosting of IRE1 signaling pathway
Authors: Shin Gu-Choul , Moon Sung Ung , Kang Hong Seok , Choi Hyo-Sun , Han Hee Dong , Kim Kyun-Hwan 
Published: July 2019

AbstractUnfolded protein response (UPR) is an adaptive mechanism that aims at restoring ER homeostasis under severe environmental stress. Malignant cells are resistant to environmental stress, which is largely due to an activated UPR. However, the molecular mechanisms by which different UPR branches are selectively controlled in tumor cells are not clearly understood. Here, we provide evidence that PRKCSH, previously known as glucosidase II beta subunit, functions as a regulator for selective activation of the IRE1α branch of UPR. PRKCSH boosts ER stress–mediated autophosphorylation and oligomerization of IRE1α through mutual interaction. PRKCSH contributes to the induction of tumor-promoting factors and to tumor resistance to ER stress. Increased levels of PRKCSH in various tumor tissues are positively correlated with the expression of XBP1-target genes. Taken together, our data provide a molecular rationale for selective activation of the IRE1α branch in tumors and adaptation of tumor cells to severe environmental stress.
Dendrite fragmentation induced by massive-like δ–γ transformation in Fe–C alloys
Authors: Yasuda Hideyuki , Morishita Kohei , Nakatsuka Noriaki , Nishimura Tomohiro , Yoshiya Masato , Sugiyama Akira , Uesugi Kentaro , Takeuchi Akihisa 
Published: July 2019

AbstractDendrite arm fragmentation is considered in solidification structure tailoring. Time-resolved and in situ imaging using synchrotron radiation X-rays allows the observation of dendrite arm fragmentation in Fe–C alloys. Here we report a dendrite arm fragmentation mechanism. A massive-like transformation from ferrite to austenite rather than the peritectic reaction occurs during or after ferrite solidification. The transformation produces refined austenite grains and ferrite–austenite boundaries in dendrite arms. The austenite grains are fragmented by the liquid phase that is produced at the grain boundary. In unidirectional solidification, a slight increase in temperature moves the ferrite–austenite interface backwards and promotes detachment of the primary and secondary arms at the δ–γ interface via a reverse peritectic reaction. The results show a massive-like transformation inducing the dendrite arm fragmentation has a role in formation of the solidification structure and the austenite grain structures in the Fe–C alloys.
Live cell imaging reveals 3′-UTR dependent mRNA sorting to synapses
Authors: Bauer Karl E. , Segura Inmaculada , Gaspar Imre , Scheuss Volker , Illig Christin , Ammer Georg , Hutten Saskia , Basyuk Eugénia , Fernández-Moya Sandra M. , Ehses Janina , Bertrand Edouard , Kiebler Michael A. 
Published: July 2019

AbstractmRNA transport restricts translation to specific subcellular locations, which is the basis for many cellular functions. However, the precise process of mRNA sorting to synapses in neurons remains elusive. Here we use Rgs4 mRNA to investigate 3′-UTR-dependent transport by MS2 live-cell imaging. The majority of observed RNA granules display 3′-UTR independent bidirectional transport in dendrites. Importantly, the Rgs4 3′-UTR causes an anterograde transport bias, which requires the Staufen2 protein. Moreover, the 3′-UTR mediates dynamic, sustained mRNA recruitment to synapses. Visualization at high temporal resolution enables us to show mRNA patrolling dendrites, allowing transient interaction with multiple synapses, in agreement with the sushi-belt model. Modulation of neuronal activity by either chemical silencing or local glutamate uncaging regulates both the 3′-UTR-dependent transport bias and synaptic recruitment. This dynamic and reversible mRNA recruitment to active synapses would allow translation and synaptic remodeling in a spatially and temporally adaptive manner.
Phase stabilization by electronic entropy in plutonium
Authors: Harrison N. , Betts J. B. , Wartenbe M. R. , Balakirev F. F. , Richmond S. , Jaime M. , Tobash P. H. 
Published: July 2019

AbstractPlutonium metal undergoes an anomalously large 25% collapse in volume from its largest volume δ phase (δ-Pu) to its low temperature α phase, yet the underlying thermodynamic mechanism has largely remained a mystery. Here we use magnetostriction measurements to isolate a previously hidden yet substantial electronic contribution to the entropy of δ-Pu, which we show to be crucial for the stabilization of this phase. The entropy originates from two competing instabilities of the 5f-electron shell, which we show to drive the volume of Pu in opposing directions, depending on the temperature and volume. Using calorimetry measurements, we establish a robust thermodynamic connection between the two excitation energies, the atomic volume, and the previously reported excess entropy of δ-Pu at elevated temperatures.
Bypassing pan-enterovirus host factor PLA2G16
Authors: Baggen Jim , Liu Yue , Lyoo Heyrhyoung , van Vliet Arno L. W. , Wahedi Maryam , de Bruin Jost W. , Roberts Richard W. , Overduin Pieter , Meijer Adam , Rossmann Michael G. , Thibaut Hendrik Jan , van Kuppeveld Frank J. M. 
Published: July 2019

AbstractEnteroviruses are a major cause of human disease. Adipose-specific phospholipase A2 (PLA2G16) was recently identified as a pan-enterovirus host factor and potential drug target. In this study, we identify a possible mechanism of PLA2G16 evasion by employing a dual glycan receptor-binding enterovirus D68 (EV-D68) strain. We previously showed that this strain does not strictly require the canonical EV-D68 receptor sialic acid. Here, we employ a haploid screen to identify sulfated glycosaminoglycans (sGAGs) as its second glycan receptor. Remarkably, engagement of sGAGs enables this virus to bypass PLA2G16. Using cryo-EM analysis, we reveal that, in contrast to sialic acid, sGAGs stimulate genome release from virions via structural changes that enlarge the putative openings for genome egress. Together, we describe an enterovirus that can bypass PLA2G16 and identify additional virion destabilization as a potential mechanism to circumvent PLA2G16.
Immune adaptor SKAP1 acts a scaffold for Polo-like kinase 1 (PLK1) for the optimal cell cycling of T-cells
Authors: Raab Monika , Strebhardt Klaus , Rudd Christopher E. 
Published: July 2019

AbstractWhile the immune cell adaptor protein SKAP1 mediates LFA-1 activation induced by antigen-receptor (TCR/CD3) ligation on T-cells, it is unclear whether the adaptor interacts with other mediators of T-cell function. In this context, the serine/threonine kinase, polo-like kinase (PLK1) regulates multiple steps in the mitotic and cell cycle progression of mammalian cells. Here, we show that SKAP1 is phosphorylated by and binds to PLK1 for the optimal cycling of T-cells. PLK1 binds to the N-terminal residue serine 31 (S31) of SKAP1 and the interaction is needed for optimal PLK1 kinase activity. Further, siRNA knock-down of SKAP1 reduced the rate of T-cell division concurrent with a delay in the expression of PLK1, Cyclin A and pH3. Reconstitution of these KD cells with WT SKAP1, but not the SKAP1 S31 mutant, restored normal cell division. SKAP1-PLK1 binding is dynamically regulated during the cell cycle of T-cells. Our findings identify a novel role for SKAP1 in the regulation of PLK1 and optimal cell cycling needed for T-cell clonal expansion in response to antigenic activation.
Changes in Alcohol Consumption and Associated Variables among Older Adults in Spain: A population-based cohort study
Authors: Soler-Vila Hosanna , Ortolá Rosario , García-Esquinas Esther , León-Muñoz Luz Mª , Rodríguez-Artalejo Fernando 
Published: July 2019

AbstractWe examined prospective changes in drinking patterns and their associations with socio-behavioral and health status variables in older adults in Spain using data from a prospective cohort of 2,505 individuals (53.3% women) representative of the non-institutionalized population aged >60 years in Spain. Alcohol consumption was assessed at baseline (2008–10) and at follow-up (2012) with a validated diet history. At risk drinking was defined as consuming >14 g of alcohol/day on average or any binge drinking in the last 30 days; lower amounts were considered light drinking. A total of 26.5% of study participants changed their intake during follow-up. Most participants reduced alcohol intake, but 23.3% of men and 8.9% of women went from light to at risk drinking during the study period. Low social connectivity at baseline was linked to at risk drinking for both sexes. However, the observed associations between changes in social connectivity, morbidity, BMI, or dietary habits and changes in drinking patterns differed by sex. We concluded that since about a quarter of older adults in Spain consume more alcohol than recommended, identifying socio-behavioral factors associated with this behavior is key for designing health campaigns targeting excessive alcohol consumption in this vulnerable population.
A whole-body Fast Field-Cycling scanner for clinical molecular imaging studies
Authors: Broche Lionel M. , Ross P. James , Davies Gareth R. , MacLeod Mary-Joan , Lurie David J. 
Published: July 2019

AbstractFast Field-Cycling (FFC) is a well-established Nuclear Magnetic Resonance (NMR) technique that exploits varying magnetic fields to quantify molecular motion over a wide range of time scales, providing rich structural information from nanometres to micrometres, non-invasively. Previous work demonstrated great potential for FFC-NMR biomarkers in medical applications; our research group has now ported this technology to medical imaging by designing a whole-body FFC Magnetic Resonance Imaging (FFC-MRI) scanner capable of performing accurate measurements non-invasively over the entire body, using signals from water and fat protons. This is a unique tool to explore new biomarkers related to disease-induced tissue remodelling. Our approach required making radical changes in the design, construction and control of MRI hardware so that the magnetic field is switched within 12.5 ms to reach any field strength from 50 μT to 0.2 T, providing clinically useful images within minutes. Pilot studies demonstrated endogenous field-dependant contrast in biological tissues in good agreement with reference data from other imaging modalities, confirming that our system can perform multiscale structural imaging of biological tissues, from nanometres to micrometres. It is now possible to confirmex vivoresults obtained from previous clinical studies, offering applications in diagnosis, staging and monitoring treatment for cancer, stroke, osteoarthritis and oedema.
Mass screening for colorectal cancer in a population of two million older adults in Guangzhou, China
Authors: Lin Guozhen , Feng Zhiqiang , Liu Huazhang , Li Yan , Nie Yuqiang , Liang Yingru , Li Ke 
Published: July 2019

AbstractScreening is an effective measure to prevent and control colorectal cancer (CRC). A mass CRC screening programme was conducted in Guangzhou from 2015 to 2017. Public media and reminders from a mobile short message service were used to invite residents aged between 50 and 74 years. A high-risk factor questionnaire (HRFQ) and biennial faecal immunochemical testing (FIT) were chosen as the primary screening methods, and individuals with a positive test result were referred to a defined hospital for an assessment colonoscopy. During the 3 years, 350,581 residents of the total eligible population of 2,283,214 attended the free first stage of screening. In all, 91.0% of the participants finished the HRFQs and FITs. The total uptake rate was 15.4%, which increased with age, female sex, and rural location. There was 15.9% positivity in the first stage of screening, including 8.5% positive HRFQs, 6.2% positive FITs and 1.2% positive HRFQs and FITs. In total, 10,600 individuals with positive HRFQs/FITs completed an assessment colonoscopy. The total uptake rate of colonoscopies was 18.9%, which decreased with age and female sex. Three hundred fifty-one CRCs and 980 advanced adenomas (AAs) were diagnosed with positive predictive values (PPV) of 3.3% and 9.2%, respectively. The PPVs of CRCs in the exclusively FIT-positive population were 4.9%, which was 10 times greater than in the exclusively HRFQ-positive population (0.5%). The PPVs of CRCs and AAs increased with age and male sex. The detection ratio of localized CRCs (including stage I and stage II) increased 68.1% due to screening. Although the compliance rate was low, the PPVs for CRCs and AAs were high. More effective mobilization of the programme’s needs and subsidies for colonoscopies should be taken into account to increase compliance.
Resting-state prefrontal EEG biomarkers in correlation with MMSE scores in elderly individuals
Authors: Choi Jungmi , Ku Boncho , You Young Gooun , Jo Miok , Kwon Minji , Choi Youyoung , Jung Segyeong , Ryu Soyoung , Park Eunjeong , Go Hoyeon , Kim Gahye , Cha Wonseok , Kim Jaeuk U. 
Published: July 2019

AbstractWe investigated whether cognitive decline could be explained by resting-state electroencephalography (EEG) biomarkers measured in prefrontal regions that reflect the slowing of intrinsic EEG oscillations. In an aged population dwelling in a rural community (total = 496, males = 165, females = 331), we estimated the global cognitive decline using the Mini-Mental State Examination (MMSE) and measured resting-state EEG parameters at the prefrontal regions of Fp1 and Fp2 in an eyes-closed state. Using a tertile split method, the subjects were classified as T3 (MMSE 28–30, N = 162), T2 (MMSE 25–27, N = 179), or T1 (MMSE ≤ 24, N = 155). The EEG slowing biomarkers of the median frequency, peak frequency and alpha-to-theta ratio decreased as the MMSE scores decreased from T2 to T1 for both sexes (−5.19 ≤ t-value ≤ −3.41 for males and −7.24 ≤ t-value ≤ −4.43 for females) after adjusting for age and education level. Using a double cross-validation procedure, we developed a prediction model for the MMSE scores using the EEG slowing biomarkers and demographic covariates of sex, age and education level. The maximum intraclass correlation coefficient between the MMSE scores and model-predicted values was 0.757 with RMSE = 2.685. The resting-state EEG biomarkers showed significant changes in people with early cognitive decline and correlated well with the MMSE scores. Resting-state EEG slowing measured in the prefrontal regions may be useful for the screening and follow-up of global cognitive decline in elderly individuals.
Enhanced soil fertility, plant growth promotion and microbial enzymatic activities of vermicomposted fly ash
Authors: Usmani Zeba , Kumar Vipin , Gupta Pratishtha , Gupta Gauri , Rani Rupa , Chandra Avantika 
Published: July 2019

AbstractIt is reported that coal consumption in the Asia-Pacific region is going to increase to about 87.2 percent by 2035. Management of coal combustion residues (CCRs) generated by industries is a major bottleneck towards handling the repercussions of coal usage. The present study investigates a management technique for these potentially hazardous wastes by means of vermicomposting. In the present investigation, studies were made on the effects of various concentrations of vermicomposted fly ash (VCF) added to agricultural soil, on the growth and yield of tomato (Lycopersicon esculentum Mill.) and brinjal (Solanum melongena L.) plants. The toxicity of trace elements in VCF were estimated using coefficient of pollution and potential ecological risk index, which revealed no apparent risks to the environment. A gradual increase in VCF concentrations in the agricultural soil improved the physico-chemical properties, enzymatic activities, microbial biomass, carbon and microbial population upto 90 days after sowing of seeds. The VCF amendments significantly (p < 0.05) improved the soil quality (2.86% nitrogen and 1.05% Phosphorous) and germination percentage (82.22%) of seeds in L. esculentum and also in S. melongena. The results of this study reveal that, CCRs can be effectively managed in agriculture specially in developing economies.