bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapamycin and fasting sustain autophagy response activated by ischemia/reperfusion injury and promote retinal ganglion cell survival
Authors: Russo Rossella , Varano Giuseppe Pasquale , Adornetto Annagrazia , Nazio Francesca , Tettamanti Gianluca , Girardello Rossana , Cianfanelli Valentina , Cavaliere Federica , Morrone Luigi Antonio , Corasaniti Maria Tiziana , Cecconi Francesco , Bagetta Giacinto , Nucci Carlo 
Published: September 2018

AbstractAutophagy, the cellular process responsible for degradation and recycling of cytoplasmic components through the autophagosomal–lysosomal pathway, is fundamental for neuronal homeostasis and its deregulation has been identified as a hallmark of neurodegeneration. Retinal hypoxic–ischemic events occur in several sight-treating disorders, such as central retinal artery occlusion, diabetic retinopathy, and glaucoma, leading to degeneration and loss of retinal ganglion cells. Here we analyzed the autophagic response in the retinas of mice subjected to ischemia induced by transient elevation of intraocular pressure, reporting a biphasic and reperfusion time-dependent modulation of the process. Ischemic insult triggered in the retina an acute induction of autophagy that lasted during the first hours of reperfusion. This early upregulation of the autophagic flux limited RGC death, as demonstrated by the increased neuronal loss observed in mice with genetic impairment of basal autophagy owing to heterozygous ablation of the autophagy-positive modulator Ambra1 (Ambra1+/gt). Upregulation of autophagy was exhausted 24 h after the ischemic event and reduced autophagosomal turnover was associated with build up of the autophagic substrate SQSTM-1/p62, decreased ATG12-ATG5 conjugate, ATG4 and BECN1/Beclin1 expression. Animal fasting or subchronic systemic treatment with rapamycin sustained and prolonged autophagy activation and improved RGC survival, providing proof of principle for autophagy induction as a potential therapeutic strategy in retinal neurodegenerative conditions associated with hypoxic/ischemic stresses.
Systems biology approach reveals a link between mTORC1 and G2/M DNA damage checkpoint recovery
Authors: Hsieh Hui-Ju , Zhang Wei , Lin Shu-Hong , Yang Wen-Hao , Wang Jun-Zhong , Shen Jianfeng , Zhang Yiran , Lu Yiling , Wang Hua , Yu Jane , Mills Gordon B. , Peng Guang 
Published: September 2018

AbstractCheckpoint recovery, the process that checkpoint-arrested cells with normal DNA repair capacity resume cell cycle progression, is essential for genome stability. However, the signaling network of the process has not been clearly defined. Here, we combine functional proteomics, mathematical modeling, and molecular biology to identify mTORC1, the nutrient signaling integrator, as the determinant for G2/M checkpoint recovery. Inhibition of the mTORC1 pathway delays mitotic entry after DNA damage through KDM4B-mediated regulation of CCNB1 and PLK1 transcription. Cells with hyper-mTORC1 activity caused by TSC2 depletion exhibit accelerated G2/M checkpoint recovery. Those Tsc2-null cells are sensitive to WEE1 inhibition in vitro and in vivo by driving unscheduled mitotic entry and inducing mitotic catastrophe. These results reveal that mTORC1 functions as a mediator between nutrition availability sensing and cell fate determination after DNA damage, suggesting that checkpoint inhibitors may be used to treat mTORC1-hyperactivated tumors such as those associated with tuberous sclerosis complex.
Structural basis of neurosteroid anesthetic action on GABAA receptors
Authors: Chen Qiang , Wells Marta M. , Arjunan Palaniappa , Tillman Tommy S. , Cohen Aina E. , Xu Yan , Tang Pei 
Published: September 2018

AbstractType A γ-aminobutyric acid receptors (GABAARs) are inhibitory pentameric ligand-gated ion channels in the brain. Many anesthetics and neurosteroids act through binding to the GABAAR transmembrane domain (TMD), but the structural basis of their actions is not well understood and no resting-state GABAAR structure has been determined. Here, we report crystal structures of apo and the neurosteroid anesthetic alphaxalone-bound desensitized chimeric α1GABAAR (ELIC-α1GABAAR). The chimera retains the functional and pharmacological properties of GABAARs, including potentiation, activation and desensitization by alphaxalone. The apo-state structure reveals an unconventional activation gate at the intracellular end of the pore. The desensitized structure illustrates molecular determinants for alphaxalone binding to an inter-subunit TMD site. These structures suggest a plausible signaling pathway from alphaxalone binding at the bottom of the TMD to the channel gate in the pore-lining TM2 through the TM1–TM2 linker. The study provides a framework to discover new GABAAR modulators with therapeutic potential.
Cooperative supramolecular polymers with anthracene‒endoperoxide photo-switching for fluorescent anti-counterfeiting
Authors: Gao Zhao , Han Yifei , Wang Feng 
Published: September 2018

AbstractInnovative technologies are highly pursued for the detection and avoidance of counterfeiting in modern information society. Herein, we report the construction of photo-responsive supramolecular polymers toward fluorescent anti-counterfeit applications, by taking advantage of multicycle anthracene‒endoperoxide switching properties. Due to σ-metalation effect, photo-oxygenation of anthracene to endoperoxide is proceeded under the mild visible light irradiation conditions, while the backward conversion occurs spontaneously at room temperature. Supramolecular polymers are formed with cooperative nucleation‒elongation mechanism, which facilitate fluorescence resonance energy transfer process via two-component co-assembly strategy. Fluorescence resonance energy transfer efficiency is delicately regulated by either light-triggered anthracene‒endoperoxide conversion or vapor-induced monomer–polymer transition, leading to high-contrast fluorescent changes among three different states. On this basis, dual-mode anti-counterfeiting patterns have been successfully fabricated via inkjet printing techniques. Hence, cooperative supramolecular polymerization of photo-fluorochromic molecules represents an efficient approach toward high-performance anti-counterfeit materials with enhanced security reliability, fast response, and ease of operation.
Resonant torsion magnetometry in anisotropic quantum materials
Authors: Modic K. A. , Bachmann Maja D. , Ramshaw B. J. , Arnold F. , Shirer K. R. , Estry Amelia , Betts J. B. , Ghimire Nirmal J. , Bauer E. D. , Schmidt Marcus , Baenitz Michael , Svanidze E. , McDonald Ross D. , Shekhter Arkady , Moll Philip J. W. 
Published: September 2018

AbstractUnusual behavior in quantum materials commonly arises from their effective low-dimensional physics, reflecting the underlying anisotropy in the spin and charge degrees of freedom. Here we introduce the magnetotropic coefficient k = ∂2F/∂θ2, the second derivative of the free energy F with respect to the magnetic field orientation θ in the crystal. We show that the magnetotropic coefficient can be quantitatively determined from a shift in the resonant frequency of a commercially available atomic force microscopy cantilever under magnetic field. This detection method enables part per 100 million sensitivity and the ability to measure magnetic anisotropy in nanogram-scale samples, as demonstrated on the Weyl semimetal NbP. Measurement of the magnetotropic coefficient in the spin-liquid candidate RuCl3 highlights its sensitivity to anisotropic phase transitions and allows a quantitative comparison to other thermodynamic coefficients via the Ehrenfest relations.
A modified serine cycle in Escherichia coli coverts methanol and CO2 to two-carbon compounds
Authors: Yu Hong , Liao James C. 
Published: September 2018

AbstractMicrobial utilization of renewable one-carbon compounds, such as methane, methanol, formic acid, and CO2, has emerged as a potential approach to increase the range of carbon sources for bioproduction and address climate change issues. Here, we modify the natural serine cycle present in methylotrophs and build an adapted pathway forEscherichia coli, which allows microorganism to condense methanol (or formate) together with bicarbonate to produce various products. We introduce the modified cycle intoE. coliand demonstrate its capability for one-carbon assimilation through growth complementation and isotope labeling experiments. We also demonstrate conversion of methanol to ethanol by utilizing the modified serine cycle in an engineeredE. colistrain, achieving a reaction yet to be accomplished by a one-pot chemical process. This work provides a platform to utilize various renewable one-carbon compounds as carbon sources for biosynthesis through a modified serine cycle inE. coli.
Mechanism-based rescue of Munc18-1 dysfunction in varied encephalopathies by chemical chaperones
Authors: Guiberson Noah Guy Lewis , Pineda André , Abramov Debra , Kharel Parinati , Carnazza Kathryn E. , Wragg Rachel T. , Dittman Jeremy S. , Burré Jacqueline 
Published: September 2018

AbstractHeterozygous de novo mutations in the neuronal protein Munc18-1 are linked to epilepsies, intellectual disability, movement disorders, and neurodegeneration. These devastating diseases have a poor prognosis and no known cure, due to lack of understanding of the underlying disease mechanism. To determine how mutations in Munc18-1 cause disease, we use newly generated S. cerevisiae strains, C. elegans models, and conditional Munc18-1 knockout mouse neurons expressing wild-type or mutant Munc18-1, as well as in vitro studies. We find that at least five disease-linked missense mutations of Munc18-1 result in destabilization and aggregation of the mutant protein. Aggregates of mutant Munc18-1 incorporate wild-type Munc18-1, depleting functional Munc18-1 levels beyond hemizygous levels. We demonstrate that the three chemical chaperones 4-phenylbutyrate, sorbitol, and trehalose reverse the deficits caused by mutations in Munc18-1 in vitro and in vivo in multiple models, offering a novel strategy for the treatment of varied encephalopathies.
Population-based study of LAMA monotherapy effectiveness compared with LABA/LAMA as initial treatment for COPD in primary care
Authors: Barrecheguren Miriam , Monteagudo Mónica , Miravitlles Marc 
Published: September 2018

AbstractThis epidemiological study aimed to describe and compare the characteristics and outcomes of COPD patients starting treatment with a long-acting anti-muscarinic (LAMA) or a combination of a long-acting beta-2 agonist (LABA)/LAMA in primary care in Catalonia (Spain) over a one-year period. Data were obtained from the Information System for the Development in Research in Primary Care (SIDIAP), a population database containing information of 5.8 million inhabitants (80% of the population of Catalonia). Patients initiating treatment with a LAMA or LABA/LAMA in 2015 were identified, and information about demographic and clinical characteristics was collected. Then, patients were matched 1:1 for age, sex, FEV1%, history of exacerbations, history of asthma and duration of treatment, and the outcomes between the two groups were compared. During 2015, 5729 individuals with COPD started treatment with a LAMA (69.8%) or LAMA/LABA (30.2%). There were no remarkable differences between groups except for a lower FEV1 and more previous hospital admissions in individuals on LABA/LAMA. The number of tests and referrals was low and decreased in both groups during follow-up. For the same severity status, the evolution was similar with a reduction in exacerbations in both groups. Treatment was changed during follow-up in up to 34.2% of patients in the LABA/LAMA and 26.3% in the LAMA group, but adherence was equally good for both. Our results suggest that initial therapy with LAMA in monotherapy may be adequate in a significant group of mild to moderate patients with COPD and a low risk of exacerbations managed in primary care.
Changes in circRNA expression profiles related to the antagonistic effects of Escherichia coli F17 in lamb spleens
Authors: Jin Chengyan , Bao Jianjun , Wang Yue , Chen Weihao , Zou Shuangxia , Wu Tianyi , Wang Lihong , Lv Xiaoyang , Gao Wen , Wang Buzhong , Zhu Guoqiang , Dai Guojun , Shi Dongfang , Sun Wei 
Published: September 2018

AbstractSheep colibacillosis is one of the most common bacterial diseases in large-scale sheep farms. In this study, we orally administered Escherichia coli F17 (E. coli F17) to lambs to obtain antagonistic and sensitive individuals. We used RNA-seq to screen for differential circRNAs in the spleens of both antagonist and sensitive individuals to explore the effect of circRNA on anti-diarrhoea in sheep. The results showed that 60 differentially expressed (DE) circRNAs were screened by RNA-seq in the spleen of antagonistic and sensitive lambs, among which 31 were up-regulated and 29 were down-regulated; q-PCR was used to validate the relative expression levels of six randomly selected circRNAs in antagonist and susceptible lambs and found to be consistent with the results of RNA-seq. Using Miranda analysis of circRNA-miRNA-mRNA interactions, we found a certain target relationship between 6 circRNAs, 5 miRNAs and 9 mRNAs. The relative expression levels of mRNA in antagonistic and sensitive lambs were verified by q-PCR and were consistent with the results of RNA-seq. This study explored the expression profile of circRNA in the spleen of an antagonistic and susceptible lamb with diarrhoea and found that differentially expressed circRNAs were helpful for determining how the lambs resist the pathogenesis of diarrhoea and provided a scientific basis for lambs to resist diarrhoea.
Runge-Kutta 4th-order method analysis for viscoelastic Oldroyd 8-constant fluid used as coating material for wire with temperature dependent viscosity
Authors: Khan Zeeshan , Rasheed Haroon Ur , Tlili Iskander , Khan Ilyas , Abbas Tariq 
Published: September 2018

AbstractPolymer flow during wire coating dragged from a bath of viscoelastic incompreesible and laminar fluid inside pressure type die is carried out numerically. In wire coating the flow depends on the velcocity of the wire, geometry of the die and viscosity of the fluid. The governing equations expressing the heat transfer and flow solved numerically by Runge-Kutta fourth order method with shooting technique. Reynolds model and Vogel’s models are encountered for temperature dependent viscosity. The umerical solutions are obtained for velocity field and temperature distribution. It is seen that the non-Newtonian parameter of the fluid accelerates the velcoty profile in the absence of porous and magnetic parameters. For large value of magnetic parameter the reverse effect is observed. It is observed that the temperature profiles decreases with increasing psedoplastic parameter in the presence and absence of porous matrix as well as magnetic parameter. The Brinkman number contributes to increase the temperature for both Reynolds and Vogel’smmodels. With the increasing of pressure gradient parameter of both Reynolds and Vogel’s models, the velocity and temperature profile increases significantly in the presence of non-Newtonian parameter. The solutions are computed for different physical parameters. Furthermore, the present result is also compared with published results as a particular case.
A dual role for the transcription factor Sp8 in postnatal neurogenesis
Authors: Gaborieau Elodie , Hurtado-Chong Anahi , Fernández Maria , Azim Kasum , Raineteau Olivier 
Published: September 2018

AbstractNeural stem cells (NSCs) of the postnatal subventricular zone (SVZ) continue producing distinct subtypes of olfactory bulb (OB) interneurons throughout life. Understanding the transcriptional coding of this diversity remains a great challenge of modern neurosciences. Interneurons expressing calretinin (CalR) represent the main interneuron subtype produced in the glomerular cell layer (GL) after birth. Previous studies have suggested that their specification relies on expression of the transcription factor Sp8 by SVZ NSCs. In this study, we performed fate mapping of NSCs that generate CalR+ or non-CalR+ interneurons, in order to assess the pattern of Sp8 expression during postnatal neurogenesis. We highlight a complex pattern of Sp8 expression, which appears to be expressed in all interneurons lineages, before getting gradually restricted to maturing CalR+ interneurons. To decipher the early and late functions of Sp8 in postnatal OB neurogenesis, we combined transient, permanent and conditional genetic approaches to manipulate Sp8 at distinct neurogenic stages. While Sp8 plays an early role in controlling proliferation in all lineages, it is not involved in the early specification of CalR+ periglomerular interneurons, but plays a crucial role in their long term survival. Together, our results highlight a crucial and dual role for Sp8 during postnatal neurogenesis.
qSE7 is a major quantitative trait locus (QTL) influencing stigma exsertion rate in rice (Oryza sativa L.)
Authors: Zhang Keqin , Zhang Yingxin , Wu Weixun , Zhan Xiaodeng , Anis Galal Bakr , Rahman Md Habibur , Hong Yongbo , Riaz Aamir , Zhu Aike , Cao Yongrun , Sun Lianping , Yang Zhengfu , Yang Qinqin , Cao Liyong , Cheng Shihua 
Published: September 2018

AbstractStigma exsertion is a key determinant to increase the efficiency of commercial hybrid rice seed production. The major quantitative trait locus (QTL) qSE7 for stigma exsertion rate was previously detected on the chromosome 7 using 75 Chromosome Segment Substitution Lines (CSSLs) derived from a cross between the high stigma exsertion indica maintainer XieqingzaoB (XQZB) and low stigma exsertion indica restorer Zhonghui9308 (ZH9308). The C51 line, a CSSL population with an introgression from XQZB, was backcrossed with ZH9308 to produce the secondary F2 (BC5F2) and F2:3 (BC5F2:3) populations. As a result, the Near Isogenic Line (NIL qSE7XB) was developed. Analysis indicated qSE7 acted as a single Mendelian factor and decreased the stigma exsertion. We hypothesized qSE7 regulates single, dual, and total stigma exsertion rate, provided experimental support. qSE7 was mapped and localized between RM5436 and RM5499 markers, within a physical distance of 1000-kb. With use of new insertion-deletion (InDel) markers and analysis of the heterozygous and phenotypic data, it was ultimately dissected to a 322.9-kb region between InDel SER4-1 and RM5436. The results are useful for additional identification and isolation of this candidate gene controlling stigma exsertion rate, and provide a basis for further fine mapping, gene cloning, and Marker Assisted Selection (MAS) breeding later.
Involvement of DHH and GLI1 in adrenocortical autograft regeneration in rats
Authors: Takizawa Nae , Tanaka Susumu , Oe Souichi , Koike Taro , Yoshida Takashi , Hirahara Yukie , Matsuda Tadashi , Yamada Hisao 
Published: September 2018

AbstractBilateral adrenalectomy forces the patient to undergo glucocorticoid replacement therapy and bear a lifetime risk of adrenal crisis. Adrenal autotransplantation is considered useful to avoid adrenal crisis and glucocorticoid replacement therapy. However, the basic process of regeneration in adrenal autografts is poorly understood. Here, we investigated the essential regeneration factors in rat adrenocortical autografts, with a focus on the factors involved in adrenal development and steroidogenesis, such as Hh signalling. A remarkable renewal in cell proliferation and increase in Cyp11b1, which encodes 11-beta-hydroxylase, occurred in adrenocortical autografts from 2–3 weeks after autotransplantation. Serum corticosterone and adrenocorticotropic hormone levels were almost recovered to sham level at 4 weeks after autotransplantation. The adrenocortical autografts showed increased Dhh expression at 3 weeks after autotransplantation, but not Shh, which is the only Hh family member to have been reported to be expressed in the adrenal gland. Increased Gli1 expression was also found in the regenerated capsule at 3 weeks after autotransplantation. Dhh and Gli1 might function in concert to regenerate adrenocortical autografts. This is the first report to clearly show Dhh expression and its elevation in the adrenal gland.
Universal cancer screening: revolutionary, rational, and realizable
Authors: Ahlquist David A. 
Published: September 2018

AbstractCancer remains the second leading cause of mortality worldwide, and overall cancer-related deaths are increasing. Despite the survival benefit from early detection, screening has to date targeted only those few organs that harbor tumors of sufficient prevalence to show cost-effectiveness at population levels, leaving most cancer types unscreened. In this perspective overview, a case is made for universal cancer screening as a logical and more inclusive approach with potentially high impact. The centrally important conceptual drivers to universal screening are biological and epidemiological. The shared biology of tumor marker release into a common distant medium, like blood, can be exploited for multi-cancer detection from a single test. And, by aggregating prevalence rates, universal screening allows all cancers (including less common ones) to be included as targets, increases screening efficiency and integration across tumor types, and potentially improves cost-effectiveness over single-organ approaches. The identification of new tumor marker classes with both broad expression across tumor types and site-prediction, remarkable advances in assay technologies, and compelling early clinical data increase the likelihood of actualizing this new paradigm. Multi-organ screening could be achieved by targeting markers within or stemming from the circulation (including blood, urine, saliva, and expired breath) or those exfoliated into common excretory pathways (including the gastrointestinal and female reproductive tracts). Rigorous clinical studies in intended use populations and collaborations between academia, industry, professional societies, and government will be required to bring this lofty vision to a population application.
Electronic origin of hydrogen storage in MOF-covered palladium nanocubes investigated by synchrotron X-rays
Authors: Chen Yanna , Sakata Osami , Nanba Yusuke , Kumara Loku Singgappulige Rosantha , Yang Anli , Song Chulho , Koyama Michihisa , Li Guangqin , Kobayashi Hirokazu , Kitagawa Hiroshi 
Published: September 2018

AbstractHybrid materials composed of metal nanoparticles and metal-organic frameworks have attracted attention for various applications because of the synergistic functionality between their constituent materials. Interfacial interaction is expected however the mechanism remains ambiguous. Here we report the valence bands of palladium nanocubes covered by copper(II) 1, 3, 5-benzenetricarboxylate (HKUST-1), denoted as Pd@HKUST-1, and the charge transfer from the palladium nanocubes to HKUST-1 at the Pd/HKUST-1 interface is investigated quantitatively. Interfacial density of states are different from those of internal constituents and imply that the Cu–O group in HKUST-1 acts as a charge accepter. The role of Cu–O group in charge transfer behaviour is also observed experimentally. Finally, we reveal the charge transfer mechanism from the Pd 4dbands to the Cu 3d(4sp) – O 2phybridization bands of HKUST-1 at the Pd/HKUST-1 interface, which explains the enhanced hydrogen storage capacity in Pd@HKUST-1.