bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal intake of oleanolic acid attenuates the subsequent development of high fructose diet-induced non-alcoholic fatty liver disease in rats
Authors: Nyakudya T. T. , Mukwevho E. , Nkomozepi P. , Erlwanger K. H. 
Published: May 2018

AbstractDietary manipulations during the early postnatal period are associated with the development of metabolic disorders including non-alcoholic fatty liver disease (NAFLD) or long-term protection against metabolic dysfunction. We investigated the potential hepatoprotective effects of neonatal administration of oleanolic acid (OA), a phytochemical, on the subsequent development in adulthood, of dietary fructose-induced NAFLD. Male and female suckling rats (n=112) were gavaged with; distilled water (DW), OA (60 mg/kg), high fructose solution (HF; 20% w/v) and OA+HF (OAHF) for 7 days. The rats were weaned onto normal rat chow on day 21 up to day 55. From day 56, half of the rats in each treatment group were continued on plain water or HF as drinking fluid for 8 weeks. Hepatic lipid accumulation and hepatic histomorphometry were then determined. Fructose consumption in adulthood following neonatal fructose intake (HF+F) caused a 47–49% increase in hepatic lipid content of both male and female rats (P<0.05). However, fructose administered in adulthood only, caused a significant increase (P<0.05) in liver lipid content in females only. NAFLD activity scores for inflammation and steatosis were higher in the fructose-fed rats compared with other groups (P<0.05). Steatosis, low-grade inflammation and fibrosis were observed in rats that received HF+F. NAFLD area fraction for fibrosis was three times higher in rats that received fructose neonatally and in adulthood compared with the rats in the negative control group (P<0.05). Treatment with OA during a critical window of developmental plasticity in rats prevented the development of fructose-induced NAFLD.
An Initial Examination of Parent Satisfaction Following Intensive Rehabilitation for Pediatric Chronic Pain
Authors: Buchannan Kristen , Banez Gerard A. , Benore Ethan , Senders Pam , Coker Clarence 
Published: May 2018

The purpose of this research was to examine global judgment of satisfaction with an intensive interdisciplinary pain treatment (IIPT) program for adolescents. The program combined inpatient and day hospital care and was designed to assist adolescents with chronic pain that interferes with their normal activities. Parents of 125 predominantly high school-age patients treated in the program anonymously completed a satisfaction survey shortly after discharge. The survey included 29 Likert scale items reflecting different aspects of the program and three open-ended questions regarding patient experience. The majority of parents (64% to 95%) rated the seven aspects of the IIPT “good” to “very good.” The admission process was the most highly rated aspect of the program, followed by ratings of both the treatment team and inclusion of the persons served. Clear themes emerged in parents’ open-ended responses, with the most frequent comments focused on specific program components/services, patient outcomes, and the helpfulness of staff. Parents’ recommendations suggested clear directions for specific quality improvement efforts. The most frequent request was for more of the services offered. The next highest were recommendations focused on improving the food served to patients and the need for more assistance with postdischarge planning. This research provides an example of the potential for using a mixed methods study to improve clinical care. Implications for Impact Statement Patient satisfaction has been recommended as a core outcome domain in studies of the effectiveness of treatments for chronic pain in children and adolescents. This mixed-methods study found that parents of adolescent patients were highly satisfied with an intensive interdisciplinary treatment for chronic pain. This research demonstrates the potential for qualitative research methods to evaluate patient satisfaction and improve clinical care.
Clinical isolates of the modern Mycobacterium tuberculosis lineage 4 evade host defense in human macrophages through eluding IL-1β-induced autophagy
Authors: Romagnoli Alessandra , Petruccioli Elisa , Palucci Ivana , Camassa Serena , Carata Elisabetta , Petrone Linda , Mariano Stefania , Sali Michela , Dini Luciana , Girardi Enrico , Delogu Giovanni , Goletti Delia , Fimia Gian Maria 
Published: May 2018

AbstractMycobacterium tuberculosis(Mtb), the causative agent of tuberculosis (TB), has infected over 1.7 billion people worldwide and causes 1.4 million deaths annually. Recently, genome sequence analysis has allowed the reconstruction of Mycobacterium tuberculosis complex (MTBC) evolution, with the identification of seven phylogeographic lineages: four referred to as evolutionarily “ancient”, and three “modern”. The MTBC strains belonging to “modern” lineages appear to show enhanced virulence that may have warranted improved transmission in humans over ancient lineages through molecular mechanisms that remain to be fully characterized. To evaluate the impact of MTBC genetic diversity on the innate immune response, we analyzed intracellular bacterial replication, inflammatory cytokine levels, and autophagy response in human primary macrophages infected with MTBC clinical isolates belonging to the ancient lineages 1 and 5, and the modern lineage 4. We show that, when compared to ancient lineage 1 and 5, MTBC strains belonging to modern lineage 4 show a higher rate of replication, associated to a significant production of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and induction of a functional autophagy process. Interestingly, we found that the increased autophagic flux observed in macrophages infected with modern MTBC is due to an autocrine activity of the proinflammatory cytokine IL-1β, since autophagosome maturation is blocked by an interleukin-1 receptor antagonist. Unexpectedly, IL-1β-induced autophagy is not disadvantageous for the survival of modernMtbstrains, which reside within Rab5-positive phagosomal vesicles and avoid autophagosome engulfment. Altogether, these results suggest that autophagy triggered by inflammatory cytokines is compatible with a high rate of intracellular bacilli replication and may therefore contribute to the increased pathogenicity of the modern MTBC lineages.
FAM188B enhances cell survival via interaction with USP7
Authors: Choi Eun-Seok , Lee Hanna , Sung Jee Young , Lee Chang-Hun , Jang Hyonchol , Kim Kyung Tae , Kim Yong-Nyun , Kim Hyoung-Pyo , Goh Sung-Ho 
Published: May 2018

AbstractWe have previously reported that FAM188B showed significant differential exon usage in cancers (NCBI GEO GSE30727), but the expression and function of FAM188B is not well characterized. In the present study, we explored the functions of FAM188B by a knockdown strategy, using siRNAs specific for FAM188B in colon cancer cell lines. FAM188B is a novel gene that encodes a protein that is evolutionarily conserved among mammals. Its mRNA has been found to be highly expressed in most solid tumors, including colorectal cancer. FAM188B knockdown induced cell growth inhibition due to an increase in apoptosis in colon cancer cell lines. Interestingly, siFAM188B treatment induced the upregulation and activation of p53, and consequently increased p53-regulated pro-apoptotic proteins, PUMA and BAX. Proteomic analysis of FAM188B immunocomplexes revealed p53 and USP7 as putative FAM188B-interacting proteins. Deletion of the putative USP7-binding motif in FAM188B reduced complex formation of FAM188B with USP7. It is noteworthy that FAM188B knockdown resulted in a decrease in overall ubiquitination in the p53 immunocomplexes, as well as p53 ubiquitination, because USP7 is involved in p53 deubiquitination. FAM188B knockdown inhibited both colony formation and anchorage-independent growth in vitro. In addition, FAM188B knockdown by siRNA reduced tumor growth in xenografted mice, with an increase in p53 proteins. Taken together, our data suggest that FAM188B is a putative oncogene that functions via interaction with USP7. Therefore, control of FAM188B could be a possible target to inhibit tumor growth.
OGG1-initiated base excision repair exacerbates oxidative stress-induced parthanatos
Authors: Wang Ruoxi , Li Chunshuang , Qiao Ping , Xue Yaoyao , Zheng Xu , Chen Hongyu , Zeng Xianlu , Liu Wenguang , Boldogh Istvan , Ba Xueqing 
Published: May 2018

AbstractOxidative stress-induced DNA damage has been well acknowledged as a major cause leading to cell death, which is etiologically linked to ischemic injury and degenerative alterations. The most common oxidation product of DNA is base lesion 8-oxo-7,8-dihydroguanine (8-oxoG), which is repaired by 8-oxoG glycosylase1 (OGG1)-initiated baseexcision repair (BER) pathway (OGG1-BER); however, the role of OGG1-BER in oxidative stress-induced cell death is poorly investigated. DNA strand breaks and apurinic/apyrimidinic (AP) sites are effective substrates to activate DNA damage sensor poly(ADP-ribose) polymerase 1 (PARP1). Overactivation of PARP1 is associated with apoptosis-inducing factor (AIF)-mediated and caspase-independent cell death (parthanatos). We hypothesized that after an excessive oxidative insult, OGG1-BER-generated strand breaks result in hyperactivation of PARP1 and consequently cell death. To test, wild type, knockout, siRNA-depleted MEFs and neuroblastoma cells, or those expressing repair-deficient OGG1 mutants were oxidatively stressed and the role of OGG1 was examined. Results showed that OGG1-BER further increases the levels of ROS-induced DNA damage by generating repair intermediates, leading to PARP1 overactivation and cell death. Cells lacking or expressing repair-deficient OGG1 showed lower levels of DNA strand lesions, PARP1 activation, and nuclear translocation of apoptosis-inducing factor, resulting in the increased resistance to ROS-induced parthanatos. These results suggested that OGG1 guards genome integrity through either lesion repair or elimination of cells with malignant potential, to maintain the homeostasis of the host, which might depend on the magnitude of guanine oxidation.
ATG5 overexpression is neuroprotective and attenuates cytoskeletal and vesicle-trafficking alterations in axotomized motoneurons
Authors: Leiva-Rodríguez Tatiana , Romeo-Guitart David , Marmolejo-Martínez-Artesero Sara , Herrando-Grabulosa Mireia , Bosch Assumpció , Forés Joaquim , Casas Caty 
Published: May 2018

AbstractInjured neurons should engage endogenous mechanisms of self-protection to limit neurodegeneration. Enhancing efficacy of these mechanisms or correcting dysfunctional pathways may be a successful strategy for inducing neuroprotection. Spinal motoneurons retrogradely degenerate after proximal axotomy due to mechanical detachment (avulsion) of the nerve roots, and this limits recovery of nervous system function in patients after this type of trauma. In a previously reported proteomic analysis, we demonstrated that autophagy is a key endogenous mechanism that may allow motoneuron survival and regeneration after distal axotomy and suture of the nerve. Herein, we show that autophagy flux is dysfunctional or blocked in degenerated motoneurons after root avulsion. We also found that there were abnormalities in anterograde/retrograde motor proteins, key secretory pathway factors, and lysosome function. Further, LAMP1 protein was missorted and underglycosylated as well as the proton pump v-ATPase. In vitro modeling revealed how sequential disruptions in these systems likely lead to neurodegeneration. In vivo, we observed that cytoskeletal alterations, induced by a single injection of nocodazole, were sufficient to promote neurodegeneration of avulsed motoneurons. Besides, only pre-treatment with rapamycin, but not post-treatment, neuroprotected after nerve root avulsion. In agreement, overexpressing ATG5 in injured motoneurons led to neuroprotection and attenuation of cytoskeletal and trafficking-related abnormalities. These discoveries serve as proof of concept for autophagy-target therapy to halting the progression of neurodegenerative processes.
Precise synthesis of sulfur-containing polymers via cooperative dual organocatalysts with high activity
Authors: Zhang Cheng-Jian , Wu Hai-Lin , Li Yang , Yang Jia-Liang , Zhang Xing-Hong 
Published: May 2018

AbstractMetal-free and controlled synthesis of sulfur-containing polymer is still a big challenge in polymer chemistry. Here, we report a metal-free, living copolymerization of carbonyl sulfide (COS) with epoxides via the cooperative catalysis of organic Lewis pairs including bases (e.g.: phosphazene, amidine, and guanidine) and thioureas as hydrogen-bond donors, afford well-defined poly(monothiocarbonate)s with 100% alternating degree, >99% tail-to-head content, controlled molecular weights (up to 98.4 kg/mol), and narrow molecular weight distributions (1.13–1.23). The effect of the types of Lewis pairs on the copolymerization of COS with several epoxides is investigated. The turnover frequencies (TOFs) of these Lewis pairs are as high as 112 h−1 at 25 °C. Kinetic and mechanistic results suggest that the supramolecular specific recognition of thiourea to epoxide and base to COS promote the copolymerization cooperatively. This strategy provides commercially available Lewis pairs for metal-free synthesis of sulfur-containing polymers with precise structure.
Circulating microRNAs as potential diagnostic biomarkers for osteoporosis
Authors: Mandourah Abdullah Y. , Ranganath Lakshminarayan , Barraclough Roger , Vinjamuri Sobhan , Hof Robert Van’T , Hamill Sandra , Czanner Gabriela , Dera Ayed A. , Wang Duolao , Barraclough Dong L. 
Published: May 2018

AbstractOsteoporosis is the most common age-related bone disease worldwide and is usually clinically asymptomatic until the first fracture happens. MicroRNAs are critical molecular regulators in bone remodelling processes and are stabilised in the blood. The aim of this project was to identify circulatory microRNAs associated with osteoporosis using advanced PCR arrays initially and the identified differentially-expressed microRNAs were validated in clinical samples using RT-qPCR. A total of 161 participants were recruited and 139 participants were included in this study with local ethical approvals prior to recruitment. RNAs were extracted, purified, quantified and analysed from all serum and plasma samples. Differentially-expressed miRNAs were identified using miRNA PCR arrays initially and validated in 139 serum and 134 plasma clinical samples using RT-qPCR. Following validation of identified miRNAs in individual clinical samples using RT-qPCR, circulating miRNAs, hsa-miR-122-5p and hsa-miR-4516 were statistically significantly differentially-expressed between non-osteoporotic controls, osteopaenia and osteoporosis patients. Further analysis showed that the levels of these microRNAs were associated with fragility fracture and correlated with the low bone mineral density in osteoporosis patients. The results show that circulating hsa-miR-122-5p and hsa-miR-4516 could be potential diagnostic biomarkers for osteoporosis in the future.
Ubiquitin Proteasome pathway proteins as potential drug targets in parasite Trypanosoma cruzi
Authors: Gupta Ishita , Aggarwal Suruchi , Singh Kanika , Yadav Amit , Khan Sameena 
Published: May 2018

AbstractTrypanosomiasis infects more than 21 million people and claims approximately 2 million lives annually. Due to the development of resistance against currently available anti-trypanosomal drugs, there is a growing need for specific inhibitors and novel drug targets. Of late, the proteins from the Ubiquitin Proteasome Pathway (UPP): ubiquitin ligases and deubiquitinase have received attention as potential drug targets in other parasites from the apicomplexan family. The completion of Trypanosoma cruzi (Tc) genome sequencing in 2005 and subsequent availability of database resources like TriTrypDB has provided a platform for the systematic study of the proteome of this parasite. Here, we present the first comprehensive survey of the UPP enzymes, their homologs and other associated proteins in trypanosomes and the UPPs from T. cruzi were explored in detail. After extensive computational analyses using various bioinformatics tools, we have identified 269 putative UPP proteins in the T. cruzi proteome along with their homologs in other Trypanosoma species. Characterization of T. cruzi proteome was done based on their predicted subcellular localization, domain architecture and overall expression profiles. Specifically, unique domain architectures of the enzymes and the UPP players expressed exclusively in the amastigote stage provide a rationale for designing inhibitors against parasite UPP proteins.
Effective BAC clone anchoring with genotyping-by-sequencing and Diversity Arrays Technology in a large genome cereal rye
Authors: Borzęcka Ewa , Hawliczek-Strulak Anna , Bolibok Leszek , Gawroński Piotr , Tofil Katarzyna , Milczarski Paweł , Stojałowski Stefan , Myśków Beata , Targońska-Karasek Małgorzata , Grądzielewska Agnieszka , Smolik Miłosz , Kilian Andrzej , Bolibok-Brągoszewska Hanna 
Published: May 2018

AbstractIdentification of bacterial artificial chromosome (BAC) clones containing specific sequences is a prerequisite for many applications, such as physical map anchoring or gene cloning. Existing BAC library screening strategies are either low-throughput or require a considerable initial input of resources for platform establishment. We describe a high-throughput, reliable, and cost-effective BAC library screening approach deploying genotyping platforms which are independent from the availability of sequence information: a genotyping-by-sequencing (GBS) method DArTSeq and the microarray-based Diversity Arrays Technology (DArT). The performance of these methods was tested in a very large and complex rye genome. The DArTseq approach delivered superior results: a several fold higher efficiency of addressing genetic markers to BAC clones and anchoring of BAC clones to genetic map and also a higher reliability. Considering the sequence independence of the platform, the DArTseq-based library screening can be proposed as an attractive method to speed up genomics research in resource poor species.
Stability and reproducibility of proteomic profiles measured with an aptamer-based platform
Authors: Kim Claire H. , Tworoger Shelley S. , Stampfer Meir J. , Dillon Simon T. , Gu Xuesong , Sawyer Sherilyn J. , Chan Andrew T. , Libermann Towia A. , Eliassen A. Heather 
Published: May 2018

AbstractThe feasibility of SOMAscan, a multiplex, high sensitivity proteomics platform, for use in studies using archived plasma samples has not yet been assessed. We quantified 1,305 proteins from plasma samples donated by 16 Nurses’ Health Study (NHS) participants, 40 NHSII participants, and 12 local volunteers. We assessed assay reproducibility using coefficients of variation (CV) from duplicate samples and intra-class correlation coefficients (ICC) and Spearman correlation coefficients (r) of samples processed (i.e., centrifuged and aliquoted into separate components) immediately, 24, and 48 hours after collection, as well as those of samples collected from the same individuals 1 year apart. CVs were <20% for 99% of proteins overall and <10% for 92% of proteins in heparin samples compared to 66% for EDTA samples. We observed ICC or Spearman r (comparing immediate vs. 24-hour delayed processing) ≥0.75 for 61% of proteins, with some variation by anticoagulant (56% for heparin and 70% for EDTA) and protein class (ranging from 49% among kinases to 83% among hormones). Within-person stability over 1 year was good (ICC or Spearman r ≥ 0.4) for 91% of proteins. These results demonstrate the feasibility of SOMAscan for analyses of archived plasma samples.
Synchronization transition in neuronal networks composed of chaotic or non-chaotic oscillators
Authors: Xu Kesheng , Maidana Jean Paul , Castro Samy , Orio Patricio 
Published: May 2018

AbstractChaotic dynamics has been shown in the dynamics of neurons and neural networks, in experimental data and numerical simulations. Theoretical studies have proposed an underlying role of chaos in neural systems. Nevertheless, whether chaotic neural oscillators make a significant contribution to network behaviour and whether the dynamical richness of neural networks is sensitive to the dynamics of isolated neurons, still remain open questions. We investigated synchronization transitions in heterogeneous neural networks of neurons connected by electrical coupling in a small world topology. The nodes in our model are oscillatory neurons that – when isolated – can exhibit either chaotic or non-chaotic behaviour, depending on conductance parameters. We found that the heterogeneity of firing rates and firing patterns make a greater contribution than chaos to the steepness of the synchronization transition curve. We also show that chaotic dynamics of the isolated neurons do not always make a visible difference in the transition to full synchrony. Moreover, macroscopic chaos is observed regardless of the dynamics nature of the neurons. However, performing a Functional Connectivity Dynamics analysis, we show that chaotic nodes can promote what is known as multi-stable behaviour, where the network dynamically switches between a number of different semi-synchronized, metastable states.
QED cascade saturation in extreme high fields
Authors: Luo Wen , Liu Wei-Yuan , Yuan Tao , Chen Min , Yu Ji-Ye , Li Fei-Yu , Del Sorbo D. , Ridgers C. P. , Sheng Zheng-Ming 
Published: May 2018

AbstractUpcoming ultrahigh power lasers at 10 PW level will make it possible to experimentally explore electron-positron (e−e+) pair cascades and subsequent relativistic e−e+ jets formation, which are supposed to occur in extreme astrophysical environments, such as black holes, pulsars, quasars and gamma-ray bursts. In the latter case it is a long-standing question as to how the relativistic jets are formed and what their temperatures and compositions are. Here we report simulation results of pair cascades in two counter-propagating QED-strong laser fields. A scaling of QED cascade growth with laser intensity is found, showing clear cascade saturation above threshold intensity of ~1024 W/cm2. QED cascade saturation leads to pair plasma cooling and longitudinal compression along the laser axis, resulting in the subsequent formation of relativistic dense e−e+ jets along transverse directions. Such laser-driven QED cascade saturation may open up the opportunity to study energetic astrophysical phenomena in laboratory.