bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vocal learning promotes patterned inhibitory connectivity
Authors: Miller Mark N. , Cheung Chung Yan J. , Brainard Michael S. 
Published: December 2017

AbstractSkill learning is instantiated by changes to functional connectivity within premotor circuits, but whether the specificity of learning depends on structured changes to inhibitory circuitry remains unclear. We used slice electrophysiology to measure connectivity changes associated with song learning in the avian analog of primary motor cortex (robust nucleus of the arcopallium, RA) in Bengalese Finches. Before song learning, fast-spiking interneurons (FSIs) densely innervated glutamatergic projection neurons (PNs) with apparently random connectivity. After learning, there was a profound reduction in the overall strength and number of inhibitory connections, but this was accompanied by a more than two-fold enrichment in reciprocal FSI–PN connections. Moreover, in singing birds, we found that pharmacological manipulations of RA's inhibitory circuitry drove large shifts in learned vocal features, such as pitch and amplitude, without grossly disrupting the song. Our results indicate that skill learning establishes nonrandom inhibitory connectivity, and implicates this patterning in encoding specific features of learned movements.
Atmospheric pressure mass spectrometric imaging of live hippocampal tissue slices with subcellular spatial resolution
Authors: Kim Jae Young , Seo Eun Seok , Kim Hyunmin , Park Ji-Won , Lim Dong-Kwon , Moon Dae Won 
Published: December 2017

AbstractWe report a high spatial resolution mass spectrometry (MS) system that allows us to image live hippocampal tissue slices under open-air atmospheric pressure (AP) and ambient temperature conditions at the subcellular level. The method is based on an efficient desorption process by femtosecond (fs) laser assisted with nanoparticles and a subsequent ionization step by applying nonthermal plasma, termed AP nanoparticle and plasma assisted laser desorption ionization (AP-nanoPALDI) MS method. Combining the AP-nanoPALDI with microscopic sample scanning, MS imaging with spatial resolution of 2.9 µm was obtained. The observed AP-nanoPALDI MS imaging clearly revealed the differences of molecular composition between the apical and basal dendrite regions of a hippocampal tissue. In addition, the AP-nanoPALDI MS imaging showed the decrease of cholesterol in hippocampus by treating with methyl β-cyclodextrin, which exemplifies the potential of AP-nanoPALDI for live tissue imaging for various biomedical applications without any chemical pretreatment and/or labeling process.
PI3Kδ activates E2F1 synthesis in response to mRNA translation stress
Authors: Gnanasundram Sivakumar Vadivel , Pyndiah Slovénie , Daskalogianni Chrysoula , Armfield Kate , Nylander Karin , Wilson Joanna B. , Fåhraeus Robin 
Published: December 2017

AbstractThe c-myc oncogene stimulates ribosomal biogenesis and protein synthesis to promote cellular growth. However, the pathway by which cells sense and restore dysfunctional mRNA translation and how this is linked to cell proliferation and growth is not known. We here show that mRNA translation stress in cis triggered by the gly-ala repeat sequence of Epstein–Barr virus (EBV)-encoded EBNA1, results in PI3Kδ-dependent induction of E2F1 mRNA translation with the consequent activation of c-Myc and cell proliferation. Treatment with a specific PI3Kδ inhibitor Idelalisib (CAL-101) suppresses E2F1 and c-Myc levels and causes cell death in EBNA1-induced B cell lymphomas. Suppression of PI3Kδ prevents E2F1 activation also in non-EBV-infected cells. These data illustrate an mRNA translation stress–response pathway for E2F1 activation that is exploited by EBV to promote cell growth and proliferation, offering new strategies to treat EBV-carrying cancers.
Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase
Authors: Reckel Sina , Gehin Charlotte , Tardivon Delphine , Georgeon Sandrine , Kükenshöner Tim , Löhr Frank , Koide Akiko , Buchner Lena , Panjkovich Alejandro , Reynaud Aline , Pinho Sara , Gerig Barbara , Svergun Dmitri , Pojer Florence , Güntert Peter , Dötsch Volker , Koide Shohei , Gavin Anne-Claude , Hantschel Oliver 
Published: December 2017

AbstractThe two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study the Dbl-homology (DH) and Pleckstrin-homology (PH) domains of Bcr-Abl p210, which constitute the only structural differences to p190. Here we report high-resolution structures of the DH and PH domains and characterize conformations of the DH–PH unit in solution. Our structural and functional analyses show no evidence that the DH domain acts as a guanine nucleotide exchange factor, whereas the PH domain binds to various phosphatidylinositol-phosphates. PH-domain mutants alter subcellular localization and result in decreased interactions with p210-selective interaction partners. Hence, the PH domain, but not the DH domain, plays an important role in the formation of the differential p210 and p190 Bcr-Abl signaling networks.
The ideal harvest time for seeds of hybrid maize (Zea mays L.) XY335 and ZD958 produced in multiple environments
Authors: Gu Riliang , Li Li , Liang Xiaolin , Wang Yanbo , Fan Tinglu , Wang Ying , Wang Jianhua 
Published: December 2017

AbstractTo identify the ideal harvest time (IHT) for the seed production of XY335 and ZD958, six seed-related traits were evaluated in seeds harvested at 11 harvest stages in 8 environments. Standard germination (SG), accelerated aging germination (AAG) and cold test germination (CTG) were vigor traits; hundred-seed weight (HSW) and seed moisture content (SMC) were physiological traits; and ≥10 °C accumulated temperature from pollination to harvest (AT10ph) was an ecological trait. All the traits were significantly affected by harvest stage. The responses of SG, AAG, CTG and HSW to postponing harvest stage fit quadratic models, while SMC and AT10ph fit linear models. The IHT (indicated by the last date to reach maximum SG, AAG and CTG) were 57.97 DAP and 56.80 DAP for XY335 and ZD958, respectively. SMC and AT10ph at IHT were 33.15% and 1234 °C for XY335, and 34.98% and 1226 °C for ZD958, respectively. The period to reach the maximum HSW was 5 days later than the IHT. Compared to HSW and SMC, AT10ph had a closer relationship to the seed vigor traits. Together with the fact that AT10ph was less affected by environment, these results suggested that AT10ph may be a novel indicator for determining the IHT.
Exposure to Magnetic Field Non-Ionizing Radiation and the Risk of Miscarriage: A Prospective Cohort Study
Authors: Li De-Kun , Chen Hong , Ferber Jeannette R. , Odouli Roxana , Quesenberry Charles 
Published: December 2017

AbstractMagnetic field (MF) non-ionizing radiation is widespread and everyone is exposed to some degree. This prospective cohort study of 913 pregnant women examined the association between high MF exposure and miscarriage risk. Cox (proportional hazards) regression was used to examine the association. After controlling for multiple other factors, women who were exposed to higher MF levels had 2.72 times the risk of miscarriage (hazard ratio = 2.72, 95% CI: 1.42–5.19) than those with lower MF exposure. The increased risk of miscarriage associated with high MF was consistently observed regardless of the sources of high MF. The association was much stronger if MF was measured on a typical day of participants’ pregnancies. The finding also demonstrated that accurate measurement of MF exposure is vital for examining MF health effects. This study provides fresh evidence, directly from a human population, that MF non-ionizing radiation could have adverse biological impacts on human health.
A Multimodal Biomicroscopic System based on High-frequency Acoustic Radiation Force Impulse and Multispectral Imaging Techniques for Tumor Characterization Ex vivo
Authors: Kim Jihun , Seo Anna , Kim Jun-Young , Choi Sung Hyouk , Yoon Hyung-Jin , Kim Eunjoo , Hwang Jae Youn 
Published: December 2017

AbstractWe report a multimodal biomicroscopic system which offers high-frequency ultrasound B-mode, acoustic radiation force impulse (ARFI), and multispectral imaging for qualitative tumor characterization ex vivo. Examinations of resected tissues from diseased regions such as tumors are crucial procedures during surgical operations to treat cancer. Particularly, if tiny tumors remain at surgical sites after tumor resection, such tumors can result in unwanted outcomes, such as cancer recurrence or metastasis to other organs. To avoid this, accurate characterizations of tumors resected during surgery are necessary. To this end, we devised a multimodal biomicroscopic system including high-frequency ultrasound B-mode, ARFI, and multispectral imaging modalities to examine resected tumors with high levels of accuracy. This system was evaluated with tissue-mimicking phantoms with different mechanical properties. In addition, colorectal tumors excised from cancer patients were examined. The proposed system offers highly resolved anatomical, mechanical, chemical information pertaining to tumors, thus allowing the detection of tumor regions from the surface to deep inside tissues. These results therefore suggest that the multimodal biomicroscopic system has the potential to undertake qualitative characterizations of excised tumors ex vivo.
Identification of ARNT-regulated BIRC3 as the target factor in cadmium renal toxicity
Authors: Lee Jin-Yong , Tokumoto Maki , Hwang Gi-Wook , Lee Moo-Yeol , Satoh Masahiko 
Published: December 2017

AbstractCadmium (Cd) is an environmental contaminant that exhibits renal toxicity. The target transcription factors involved in Cd renal toxicity are still unknown. In this study, we demonstrated that Cd decreased the activity of the ARNT transcription factor, and knockdown of ARNT significantly decreased the viability of human proximal tubular HK-2 cells. Microarray analysis in ARNT knockdown cells revealed a decrease in the expression of a number of genes, including a known apoptosis inhibitor, BIRC3, whose gene and protein expression level was also decreased by Cd treatment. Although the BIRC family consists of 8 members, Cd suppressed only BIRC3 gene expression. BIRC3 is known to suppress apoptosis through the inhibition effect on caspase-3. Knockdown of BIRC3 by siRNA as well as Cd treatment increased the level of active caspase-3. Moreover, knockdown of BIRC3 not only triggered cell toxicity and apoptosis but also strengthened Cd toxicity in HK-2 cells. Meanwhile, the activation of caspase-3 by suppression of BIRC3 gene expression was mostly specific to Cd and to proximal tubular cells. These results suggest that Cd induces apoptosis through the inhibition of ARNT-regulated BIRC3 in human proximal tubular cells.
Genetic adaptation of microbial populations present in high-intensity catfish production systems with therapeutic oxytetracycline treatment
Authors: Zeng Qifan , Tian Xiangli , Wang Luxin 
Published: December 2017

AbstractMicrobial communities that are present in aquaculture production systems play significant roles in degrading organic matter, controlling diseases, and formation of antibiotic resistance. It is important to understand the diversity and abundance of microbial communities and their genetic adaptations associated with environmental physical and chemical changes. Here we collected water and sediment samples from a high-intensity catfish production system and its original water reservoir. The metagenomic analysis showed that Proteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria, and Firmicutes were the top five phyla identified from all samples. The aquaculture production system significantly changed the structure of aquatic microbial populations. Substantial changes were also observed in SNP patterns among four sample types. The gene-specific sweep was found to be more common than genome-wide sweep. The selective sweep analysis revealed that 21 antibiotic resistant (AR) genes were under selection, with most belonging to antibiotic efflux pathways. Over 200 AR gene gains and losses were determined by changes in gene frequencies. Most of the AR genes were characterized as ABC efflux pumps, RND efflux pumps, and tetracycline MFS efflux pumps. Results of this study suggested that aquaculture waste, especially waste containing therapeutic antibiotics, has a significant impact on microbial population structures and their genetic structures.
Nomogram for cirrhosis in patients with chronic hepatitis B: A simple self-assessed scale for individual risk of cirrhosis
Authors: Zhang Zhiqiao , Li Jing , Wang Peng , He Tingshan , Ouyang Yanling , Huang Yiyan 
Published: December 2017

AbstractThe aim of this retrospective study was to establish a simple self-assessed scale for individual risk of cirrhosis in patients with chronic hepatitis B. A total of 1808 consecutive patients were enrolled and analyzed. According to the results of multivariate logistic regression analysis, a simple nomogram was calculated for cirrhosis. The area under receiver operating characteristic curves (AUROCs) were calculated to compare the diagnostic accuracy of nomogram with aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the four factors (FIB-4), and S index. The AUROCs of nomogram for cirrhosis were 0.807 (adjusted AUROC 0.876) in model group and 0.794 (adjusted AUROC0.866) in validation group. DeLong’s test and Brier Score further demonstrated that nomogram was superior to APRI, FIB-4 and S index in both model group and validation group. The patients with nomogram <0.07 could be defined as low risk group with cirrhosis prevalence lower than 4.3% (17/397). The patients with nomogram >0.52 could be defined as high risk group with cirrhosis prevalence higher than 73.0% (119/163). In conclusion, as a self-assessed style, simple, non-invasive, economical, convenient, and repeatable scale, nomogram is suitable to serve as a massive health screening tool for cirrhosis in CHB patients and further external validation is needed.
Differential contributions of the middle frontal gyrus functional connectivity to literacy and numeracy
Authors: Koyama Maki S. , O’Connor David , Shehzad Zarrar , Milham Michael P. 
Published: December 2017

AbstractLiteracy and numeracy equally affect an individual’s success in and beyond schools, but these two competencies tend to be separately examined, particularly in neuroimaging studies. The current resting-state fMRI study examined the neural correlates of literacy and numeracy in the same sample of healthy adults. We first used an exploratory “Multivariate Distance Matrix Regression” (MDMR) approach to examine intrinsic functional connectivity (iFC), highlighting the middle frontal gyrus (MFG) for both competencies. Notably, there was a hemispheric asymmetry in the MDMR-based MFG findings, with literacy associated with the left MFG, whereas numeracy associated with the right MFG (R.MFG). Results of post-hoc seed-based correlation analyses further strengthened differential contributions of MFG connections to each competency. One of the most striking and novel findings from the present work was that numeracy was negatively related to R.MFG connections with the default network, which has been largely overlooked in the literature. Our results are largely consistent with prior neuroimaging work showing distinct neural mechanisms underlying literacy and numeracy, and also indicate potentially common iFC profiles to both competencies (e.g., R.MFG with cerebellum). Taken together, our iFC findings have a potential to provide novel insights into neural bases of literacy, numeracy, and impairments in these competencies.
Free-Breathing 3D Liver Perfusion Quantification Using a Dual-Input Two-Compartment Model
Authors: Ghodasara Satyam , Pahwa Shivani , Dastmalchian Sara , Gulani Vikas , Chen Yong 
Published: December 2017

AbstractThe purpose of this study is to test the feasibility of applying a dual-input two-compartment liver perfusion model to patients with different pathologies. A total of 7 healthy subjects and 11 patients with focal liver lesions, including 6 patients with metastatic adenocarcinoma and 5 with hepatocellular carcinoma (HCC), were examined. Liver perfusion values were measured from both focal liver lesions and cirrhotic tissues (from the 5 HCC patients). Compared to results from volunteer livers, significantly higher arterial fraction, fractional volume of the interstitial space, and lower permeability-surface area product were observed for metastatic lesions, and significantly higher arterial fraction and lower vascular transit time were observed for HCCs (P < 0.05). Significantly lower arterial fraction and higher vascular transit time, fractional volume of the vascular space, and fractional volume of the interstitial space were observed for metastases in comparison to HCCs (P < 0.05). For cirrhotic livers, a significantly lower total perfusion, lower fractional volume of the vascular space, higher fractional volume of the interstitial space, and lower permeability-surface area product were noted in comparison to volunteer livers (P < 0.05). Our findings support the possibility of using this model with 3D free-breathing acquisitions for lesion and diffuse liver disease characterization.
In vivo metabolic imaging of Traumatic Brain Injury
Authors: Guglielmetti Caroline , Chou Austin , Krukowski Karen , Najac Chloe , Feng Xi , Riparip Lara-Kirstie , Rosi Susanna , Chaumeil Myriam M. 
Published: December 2017

AbstractComplex alterations in cerebral energetic metabolism arise after traumatic brain injury (TBI). To date, methods allowing for metabolic evaluation are highly invasive, limiting our understanding of metabolic impairments associated with TBI pathogenesis. We investigated whether 13C MRSI of hyperpolarized (HP) [1-13C] pyruvate, a non-invasive metabolic imaging method, could detect metabolic changes in controlled cortical injury (CCI) mice (n = 57). Our results show that HP [1-13C] lactate-to-pyruvate ratios were increased in the injured cortex at acute (12/24 hours) and sub-acute (7 days) time points after injury, in line with decreased pyruvate dehydrogenase (PDH) activity, suggesting impairment of the oxidative phosphorylation pathway. We then used the colony-stimulating factor-1 receptor inhibitor PLX5622 to deplete brain resident microglia prior to and after CCI, in order to confirm that modulations of HP [1-13C] lactate-to-pyruvate ratios were linked to microglial activation. Despite CCI, the HP [1-13C] lactate-to-pyruvate ratio at the injury cortex of microglia-depleted animals at 7 days post-injury remained unchanged compared to contralateral hemisphere, and PDH activity was not affected. Altogether, our results demonstrate that HP [1-13C] pyruvate has great potential for in vivo non-invasive detection of cerebral metabolism post-TBI, providing a new tool to monitor the effect of therapies targeting microglia/macrophages activation after TBI.
Investigation of the effects of the CFTR potentiator ivacaftor on human P-glycoprotein (ABCB1)
Authors: Lingam Swathi , Thonghin Nopnithi , Ford Robert C. 
Published: December 2017

AbstractIvacaftor is a potentiator of the CFTR chloride channel and is in worldwide clinical use for the chronic treatment of cystic fibrosis in patients. There is evidence that the bioavailability of ivacaftor in the body may be influenced by the multi-drug exporter P-glycoprotein. Here we have employed purified and reconstituted P-glycoprotein to study its interaction with ivacaftor as well as the ability of the drug to compete with a known transported substrate of the protein. We find that ivacaftor stimulates the ATPase activity of the purified protein and can compete with the transport of the fluorescent substrate Hoechst 33342. These findings lead us to conclude that ivacaftor is very likely an efficiently transported substrate of P-glycoprotein. Evidence for state-dependent binding of ivacaftor was obtained using a fluorescent, cysteine-reactive reporter dye. The quiescent, nucleotide-free state in the P-glycoprotein transport cycle appears to bind ivacaftor strongly.
Metabolic engineering of the pentose phosphate pathway for enhanced limonene production in the cyanobacterium Synechocysti
s sp. PCC 6803
Authors: Lin Po-Cheng , Saha Rajib , Zhang Fuzhong , Pakrasi Himadri B. 
Published: December 2017

AbstractIsoprenoids are diverse natural compounds, which have various applications as pharmaceuticals, fragrances, and solvents. The low yield of isoprenoids in plants makes them difficult for cost-effective production, and chemical synthesis of complex isoprenoids is impractical. Microbial production of isoprenoids has been considered as a promising approach to increase the yield. In this study, we engineered the model cyanobacterium Synechocystis sp. PCC 6803 for sustainable production of a commercially valuable isoprenoid, limonene. Limonene synthases from the plants Mentha spicata and Citrus limon were expressed in cyanobacteria for limonene production. Production of limonene was two-fold higher with limonene synthase from M. spicata than that from C. limon. To enhance isoprenoid production, computational strain design was conducted by applying the OptForce strain design algorithm on Synechocystis 6803. Based on the metabolic interventions suggested by this algorithm, genes (ribose 5-phosphate isomerase and ribulose 5-phosphate 3-epimerase) in the pentose phosphate pathway were overexpressed, and a geranyl diphosphate synthase from the plant Abies grandis was expressed to optimize the limonene biosynthetic pathway. The optimized strain produced 6.7 mg/L of limonene, a 2.3-fold improvement in productivity. Thus, this study presents a feasible strategy to engineer cyanobacteria for photosynthetic production of isoprenoids.
Distribution network reconfiguration comprehensively considering N−1 security and network loss
Authors: Zu Guoqiang , Xiao Jun , Sun Kai 
Published: December 2017

Efficiency pursuit of the distribution system operation should be on the premise of security. This study proposes the network reconfiguration (NR) approach comprehensively considering N −1 security and network loss. A new approach called distribution system security region (DSSR) is first applied in NR problem. The DSSR is the feasible operation space of a system within N −1 security criterion and can quantify the N −1 security margin. Then, the NR is formulated by using the minimum network loss as objective function and the N −1 security margin, which is provided by the DSSR, as constraints. Moreover, the security margin constraints can be customised for each feeder individually, yielding proper compromises between security‐related and efficient concerns. Different NR results for multiple security and efficiency requirements are presented on an extended IEEE‐RBTS test system. Compared with the traditional minimum‐loss NR, the proposed approach reduces the network loss as much as possible with desired security margin, well balancing the security and efficiency of NR.